Asian Pacific Journal of Cancer Prevention
Asian Pacific Journal of Cancer Prevention (APOCP)
- Monthly
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- 1513-7368(pISSN)
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- 2476-762X(eISSN)
Domain
- Health Sciences > Development of Pharmaceutical
Aim & Scope
Cancer is a very complex disease. While many aspects of carcinoge-nesis and oncogenesis are known, cancer control and prevention at the community level is however still in its infancy. Much more work needs to be done and many more steps need to be taken before effective strategies are developed. The multidisciplinary approaches and efforts to understand and control cancer in an effective and efficient manner, require highly trained scientists in all branches of the cancer sciences, from cellular and molecular aspects to patient care and palliation. The Asia Pacific Organization for Cancer Prevention (APOCP) and its official publication, the Asia Pacific Journal of Cancer Prevention (APJCP), have served the community of cancer scientists very well and intends to continue to serve in this capacity to the best of its abilities. One of the objectives of the APOCP is to provide all relevant and current scientific information on the whole spectrum of cancer sciences. They aim to do this by providing a forum for communication and propagation of original and innovative research findings that have relevance to understanding the etiology, progression, treatment, and survival of patients, through their journal. The APJCP with its distinguished, diverse, and Asia-wide team of editors, reviewers, and readers, ensure the highest standards of research communication within the cancer sciences community across Asia as well as globally. The APJCP publishes original research results under the following categories: - Epidemiology, detection and screening. - Cellular research and bio-markers. - Identification of bio-targets and agents with novel mechanisms of action. - Optimal clinical use of existing anti-cancer agents, including combination therapies. - Radiation and surgery. - Palliative care. - Patient adherence, quality of life, satisfaction. - Health economic evaluations. All research and manuscript published by the Asia Pacific Journal of Cancer Prevention, are under the terms of the Creative Commons Attribution License. This permits anyone to copy, distribute, transmit and adapt the published work, provided the original work and source are appropriately cited. The APJCP strongly supports the Open Access initiative. Each published article is assigned a Crossref Digital Object Identifier (DOI), and full texts (HTML, PDF and XML format) of all articles published by the Asia Pacific Journal of Cancer Prevention, are freely accessible to everyone immediately after publication. Asia Pacific Journal of Cancer Prevention supports the Bethesda Statement on Open Access Publishing.
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Volume 16 Issue 18
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The development of new strategies for vaccine delivery for generating protective and long-lasting immune responses has become an expanding field of research. In the last years, it has been recognized that bacteriophages have several potential applications in the biotechnology and medical fields because of their intrinsic advantages, such as ease of manipulation and large-scale production. Over the past two decades, bacteriophages have gained special attention as vehicles for protein/peptide or DNA vaccine delivery. In fact, whole phage particles are used as vaccine delivery vehicles to achieve the aim of enhanced immunization. In this strategy, the carried vaccine is protected from environmental damage by phage particles. In this review, phage-based vaccine categories and their development are presented in detail, with discussion of the potential of phage-based vaccines for protection against microbial diseases and cancer treatment. Also reviewed are some recent advances in the field of phagebased vaccines.
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Wang, Ting;Li, Yu;Lu, Hai-Ling;Meng, Qing-Wei;Cai, Li;Chen, Xue-Song 8031
Background: Preclinical studies have demonstrated that${\beta}$ -adrenergic receptor antagonists could improve the prognosis of breast cancer. However, the conclusions of clinical and pharmacoepidemiological studies have been inconsistent. This review was conducted to re-assess the relationship between beta-adrenoceptor blockers and breast cancer prognosis. Materials and Methods: The literature was searched from PubMed, EMBASE and Web of Nature (Thompson Reuters) databases through using key terms, such as breast cancer and beta-adrenoceptor blockers. Results: Ten publications met the inclusion criteria. Six suggested that receiving beta-adrenoceptor blockers reduced the risk of breast cancer-specific mortality, and three of them had statistical significance (hazard ratio (HR)=0.42; 95% CI=0.18-0.97; p=0.042). Two studies reported that risk of recurrence and distant metastasis (DM) were both significantly reduced. One study demonstrated that the risk of relapse-free survival (RFS) was raised significantly with beta-blockers (BBS) (HR= 0.30; 95% CI=0.10-0.87; p=0.027). One reported longer disease-free interval (Log Rank (LR)=6.658; p=0.011) in BBS users, but there was no significant association between overall survival (OS) and BBS (HR= 0.35; 95% CI=0.12-1.0; p=0.05) in five studies. Conclusions: Through careful consideration, it is suggested that beta-adrenoceptor blockers use may be associated with improved prognosis in breast cancer patients. Nevertheless, larger size studies are needed to further explore the relationship between beta-blocker drug use and breast cancer prognosis. -
Cervical cancer is one of the most common cancers in women worldwide. During their life time the vast majority of women become infected with human papillomavirus (HPV), but interestingly only a small portion develop cervical cancer and in the remainder infection regresses to a normal healthy state. Beyond HPV status, associated molecular characterization of disease has to be established. However, initial work suggests the existence of several different molecular classes, based on the biological features of differentially expressed genes in each subtype. This suggests that additional risk factors play an important role in the outcome of infection. Host genomic factors play an important role in the outcome of such complex or multifactor diseases such as cervical cancer and are also known to regulate the rate of disease progression. The aim of this review was to compile advances in the field of host genomics of HPV positive and negative cervical cancer and their association with clinical response.
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Proteases are important molecules that are involved in many key physiological processes. Protease signaling pathways are strictly controlled, and disorders in protease activity can result in pathological changes such as cardiovascular and inflammatory diseases, cancer and neurological disorders. Many proteases have been associated with increasing tumor metastasis in various human cancers, suggesting important functional roles in the metastatic process because of their ability to degrade the extracellular matrix barrier. Proteases are also capable of cleaving non-extracellular matrix molecules. Inhibitors of proteases to some extent can reduce invasion and metastasis of cancer cells, and slow down cancer progression. In this review, we focus on the role of a few proteases and their inhibitors in tumors as a basis for cancer prognostication and therapy.
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Abdelsatir, Azza Ali;Husain, Nazik Elmalaika;Hassan, Abdallah Tarig;Elmadhoun, Wadie M;Almobarak, Ahmed O;Ahmed, Mohamed H 8053
Metformin is known as a hypoglycaemic agent that regulates glucose homeostasis by inhibiting liver glucose production and increasing muscle glucose uptake. Colorectal cancer (CRC) is one of the most common cancers worldwide, with about a million new cases diagnosed each year. The risk factors for CRC include advanced age, smoking, black race, obesity, low fibre diet, insulin resistance, and the metabolic syndrome. We have searched Medline for the metabolic syndrome and its relation to CRC, and metformin as a potential treatment of colorectal cancer. Administration of metformin alone or in combination with chemotherapy has been shown to suppress CRC. The mechanism that explains how insulin resistance is associated with CRC is complex and not fully understood. In this review we have summarised studies which showed an association with the metabolic syndrome as well as studies which tackled metformin as a potential treatment of CRC. In addition, we have also provided a summary of how metformin at the cellular level can induce changes that suppress the activity of cancer cells. -
Nasopharyngeal carcinoma (NPC) is a common tumor in southern China and south-eastern Asia. Effective strategies for the prevention or screening of NPC are limited. Exploring effective biomarkers for the early diagnosis and prognosis of NPC continues to be a rigorous challenge. Evidence is accumulating that DNA methylation alterations are involved in the initiation and progression of NPC. Over the past few decades, aberrant DNA methylation in single or multiple tumor suppressor genes (TSGs) in various biologic samples have been described in NPC, which potentially represents useful biomarkers. Recently, large-scale DNA methylation analysis by genome-wide methylation platform provides a new way to identify candidate DNA methylated markers of NPC. This review summarizes the published research on the diagnostic and prognostic potential biomarkers of DNA methylation for NPC and discusses the current knowledge on DNA methylation as a biomarker for the early detection and monitoring of progression of NPC.
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Pan, Jing-Jing;Xie, Xiao-Juan;Li, Xu;Chen, Wei 8067
Background: Long non-coding RNAs (lncRNAs) are emerging as key players in gene expression that govern cell developmental processes, and thus contributing to diseases, especially cancers. Many studies have suggested that aberrant expression of lncRNAs is responsible for drug resistance, a substantial obstacle for cancer therapy. Drug resistance not only results from individual variations in patients, but also from genetic and epigenetic differences in tumors. It is reported that drug resistance is tightly modulated by lncRNAs which change the stability and translation of mRNAs encoding factors involved in cell survival, proliferation, and drug metabolism. In this review, we summarize recent advances in research on lncRNAs associated with drug resistance and underlying molecular or cellular mechanisms, which may contribute helpful approaches for the development of new therapeutic strategies to overcome treatment failure. -
Sarcopenia, characterized by a decline of skeletal muscle plus low muscle strength and/or physical performance, has emerged to be an important prognostic factor for advanced cancer patients. It is associated with poor performance status, toxicity from chemotherapy, and shorter time of tumor control. There is limited data about sarcopenia in cancer patients and associated factors. Moreover, the knowledge about the changes of muscle mass during chemotherapy and its impact to response and toxicity to chemotherapy is still lacking. This review aimed to provide understanding about sarcopenia and to emphasize its importance to cancer treatment.
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Kaewpitoon, Soraya J;Loyd, Ryan A;Rujirakul, Ratana;Panpimanmas, Sukij;Matrakool, Likit;Tongtawee, Taweesak;Kootanavanichpong, Nusorn;Kompor, Ponthip;Chavengkun, Wasugree;Kujapun, Jirawoot;Norkaew, Jun;Ponphimai, Sukanya;Padchasuwan, Natnapa;Pholsripradit, Poowadol;Eksanti, Thawatchai;Phatisena, Tanida;Kaewpitoon, Natthawut 8079
Metformin is an oral anti-hyperglycemic agent, which is the most commonly prescribed medication in the treatment of type-2 diabetes mellitus. It is purportedly associated with a reduced risk for various cancers, mainly exerting anti-proliferation effects on various human cancer cell types, such as pancreas, prostate, breast, stomach and liver. This mini-review highlights the risk and benefit of metformin used for cholangiocarcinoma (CCA) prevention and therapy. The results indicated metformin might be a quite promising strategy CCA prevention and treatment, one mechanism being inhibition of CCA tumor growth by cell cycle arrest in both in vitro and in vivo. The AMPK/mTORC1 pathway in intrahepatic CCA cells is targeted by metformin. Furthermore, metformin inhibited CCA tumor growth via the regulation of Drosha-mediated expression of multiple carcinogenic miRNAs. The use of metformin seems to be safe in patients with cirrhosis, and provides a survival benefit. Once hepatic malignancies are already established, metformin does not offer any therapeutic potential. Clinical trials and epidemiological studies of the benefit of metformin use for CCA should be conducted. To date, whether metformin as a prospective chemotherapeutic for CCA is still questionable and waits further atttention. -
Freitas, Beatriz C;Suehiro, Tamy T;Consolaro, Marcia EL;Silva, Vania RS 8085
Human papillomavirus is a virus that is distributed worldwide, and persistent infection with high-risk genotypes (HR-HPV) is considered the most important factor for the development of squamous cell cervical carcinoma (SCC). However, by itself, it is not sufficient, and other factors may contribute to the onset and progression of lesions. For example, infection with other sexually transmitted diseases such as human immunodeficiency virus (HIV) may be a factor. Previous studies have shown the relationship between HPV infection and SCC development among HIV-infected women in many regions of the world, with great emphasis on low- and middle-income countries (LMICs). Brazil is considered a LMIC and has great disparities across different regions. The purpose of this review was to highlight the current knowledge about HPV infection and cervical abnormalities in HIV+ women in Brazil because this country is an ideal setting to evaluate HIV impact on SCC development and serves as model of LMICs and low-resource settings. -
Background: Genetic and environmental factors play important roles in pathogenesis of digestive tract cancers like those in the esophagus, stomach and colorectum. Folate deficiency and methylenetetrahydrofolate reductase (MTHFR) as an important enzyme of folate and methionine metabolism are considered crucial for DNA synthesis and methylation. MTHFR variants may cause genomic hypomethylation, which may lead to the development of cancer, and MTHFR gene polymorphisms (especially C677T and A1298C) are known to influence predispositions for cancer development. Several case control association studies of MTHFR C677T polymorphisms and colorectal cancer (CRC) have been reported in different populations with contrasting results, possibly reflecting inadequate statistical power. Aim: The present meta-analysis was conducted to investigate the association between the C677T polymorphism and the risk of colorectal cancer. Materials and Methods: A literature search of the PubMed, Google Scholar, Springer link and Elsevier databases was carried out for potential relevant articles. Pooled odds ratio (OR) with corresponding 95 % confidence interval (95 % CI) was calculated to assess the association of MTHFR C677T with the susceptibility to CRC. Cochran's Q statistic and the inconsistency index (I2) were used to check study heterogeneity. Egger's test and funnel plots were applied to assess publication bias. All statistical analyses were conducted by with MetaAnalyst and MIX version 1.7. Results: Thirty four case-control studies involving a total of 9,143 cases and 11,357 controls were retrieved according to the inclusion criteria. Overall, no significant association was found between the MTHFR C677T polymorphism and colorectal cancer in Asian populations (for T vs. C: OR=1.03; 95% CI= 0.92-1.5; p= 0.64; for TT vs CC: OR=0.88; 95%CI= 0.74-1.04; p= 0.04; for CT vs. CC: OR = 1.02; 95%CI= 0.93-1.12; p=0.59; for TT+ CT vs. CC: OR=1.07; 95%CI= 0.94-1.22; p=0.87). Conclusions: Evidence from the current meta-analysis indicated that the C677T polymorphism is not associated with CRC risk in Asian populations. Further investigations are needed to offer better insight into any role of this polymorphism in colorectal carcinogenesis.
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Magaji, Bello Arkilla;Moy, Foong Ming;Roslani, April Camilla;Law, Chee Wei;Raduan, Farhana;Sagap, Ismail 8101
Background: This study examined the psychometric properties of the Bahasa Malaysia (BM) version of the European Organization for Research and Treatment of Cancer (EORTC) Colorectal Cancer-specific Quality Of Life Questionnaire (QLQ-CR29). Materials and Methods: We studied 93 patients recruited from University Malaya and Universiti Kebangsaan Medical Centers, Kuala Lumpur, Malaysia using a self-administered method. Tools included QLQ-C30, QLQ-CR29 and Karnofsky Performance Scales (KPS). Statistical analyses included Cronbach's alpha, test-retest correlations, multi-traits scaling and known-groups comparisons. A p vaue${\leq}0.05$ was considered significant. Results: The internal consistency coefficients for body image, urinary frequency, blood and mucus and stool frequency scales were acceptable (Cronbach's alpha${\alpha}{\geq}0.65$ ). However, the coefficients were low for the blood and mucus and stool frequency scales in patients with a stoma bag (${\alpha}=0.46$ ). Test-retest correlation coefficients were moderate to high (range: r = 0.51 to 1.00) for most of the scales except anxiety, urinary frequency, buttock pain, hair loss, stoma care related problems, and dyspareunia (r${\leq}0.49$ ). Convergent and discriminant validities were achieved in all scales. Patients with a stoma reported significantly higher symptoms of blood and mucus in the stool, flatulence, faecal incontinence, sore skin, and embarrassment due to the frequent need to change the stoma bag (p < 0.05) compared to patients without stoma. None of the scales distinguished between patients based on the KPS scores. There were no overlaps between scales in the QLQ-C30 and QLQ-CR29 (r < 0.40). Conclusions: the BM version of the QLQ-CR29 indicated acceptable psychometric properties in most of the scales similar to original validation study. This questionnaire could be used to complement the QLQ-C30 in assessing HRQOL among BM speaking population with colorectal cancer. -
Magaji, Bello Arkilla;Moy, Foong Ming;Roslani, April Camilla;Law, Chee Wei;Sagap, Ismail 8107
Background and Aims: Colorectal cancer is the second most frequent cancer in Malaysia. We aimed to assess the validity and reliability of the Malaysian Chinese version of European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire core (QLQ-C30) in patients with colorectal cancer. Materials and Methods: Translated versions of the QLQ-C30 were obtained from the EORTC. A cross sectional study design was used to obtain data from patients receiving treatment at two teaching hospitals in Kuala Lumpur, Malaysia. The Malaysian Chinese version of QLQ-C30 was self-administered in 96 patients while the Karnofsky Performance Scales (KPS) was generated by attending surgeons. Statistical analysis included reliability, convergent, discriminate validity, and known-groups comparisons. Statistical significance was based on p value${\leq}0.05$ . Results: The internal consistencies of the Malaysian Chinese version were acceptable [Cronbach's alpha (${\alpha}{\geq}0.70$ )] in the global health status/overall quality of life (GHS/QOL), functioning scales except cognitive scale (${\alpha}{\leq}0.32$ ) in all levels of analysis, and social/family functioning scale (${\alpha}=0.63$ ) in patients without a stoma. All questionnaire items fulfilled the criteria for convergent and discriminant validity except question number 5, with correlation with role (r = 0.62) and social/family (r = 0.41) functioning higher than with physical functioning scales (r = 0.34). The test-retest coefficients in the GHS/QOL, functioning scales and in most of the symptoms scales were moderate to high (r = 0.58 to 1.00). Patients with a stoma reported statistically significant lower physical functioning (p=0.015), social/family functioning (p=0.013), and higher constipation (p=0.010) and financial difficulty (p=0.037) compared to patients without stoma. There was no significant difference between patients with high and low KPS scores. Conclusions: Malaysian Chinese version of the QLQ-C30 is a valid and reliable measure of HRQOL in patients with colorectal cancer. -
de la Cruz, Joseph Flores;Vergara, Emil Joseph Sanvictores;Cho, Yura;Hong, Hee Ok;Oyungerel, Baatartsogt;Hwang, Seong Gu 8113
Glehnia littoralis (GL) is widely used as an oriental medicine for cough, fever, stroke and other disease conditions. However, the anti-cancer properties of GL on MCF-7 human breast cancer cells have not been investigated. In order to elucidate anti-cancer properties and underlying cell death mechanisms, MCF-7cells ($5{\times}10^4/well$ ) were treated with Glehnia littoralis root extract at 0-400 ug/ml. A hot water extract of GL root inhibited the proliferation of MCF-7 cells in a dose-dependent manner. Analysis of the cell cycle after treatment of MCF-7 cells with increasing concentrations of GL root extract for 24 hours showed significant cell cycle arrest in the G1 phase. RT-PCR and Western blot analysis both revealed that GL root extract significantly increased the expression of p21 and p27 with an accompanying decrease in both CDK4 and cyclin D1. Our reuslts indicated that GL root extract arrested the proliferation of MCF-7 cells in G1 phase through inhibition of CDK4 and cyclin D1 via increased induction of p21 and p27. In summary, the current study showed that GL could serve as a potential source of chemotherapeutic or chemopreventative agents against human breast cancer. -
Kannan, Narayanan;Sakthivel, Kunnathur Murugesan;Guruvayoorappan, Chandrasekaran 8119
Cancer is a leading cause of death worldwide. Due to the toxic side effects of the commonly used chemotherapeutic drug cyclophosphamide (CTX), the use of herbal medicines with fewer side effects but having potential use as inducing anti-cancer outcomes in situ has become increasingly popular. The present study sought to investigate the effects of a methanolic extract of Bauhinia tomentosa against Dalton's ascites lymphoma (DAL) induced ascites as well as solid tumors in BALB/c mice. Specifically, B. tomentosa extract was administered intraperitonealy (IP) at 10 mg/kg. BW body weight starting just after tumor cell implantation and thereafter for 10 consecutive days. In the ascites tumor model hosts, administration of extract resulted in a 52% increase in the life span. In solid tumor models, co-administration of extract and CTX significantly reduced tumor volume (relative to in untreated hosts) by 73% compared to just by 52% when the extract alone was provided. Co-administration of the extract also mitigated CTX-induced toxicity, including decreases in WBC count, and in bone marrow cellularity and${\alpha}$ -esterase activity. Extract treatment also attenuated any increases in serum levels of$TNF{\alpha}$ , iNOS, IL-$1{\beta}$ , IL-6, GM-CSF, and VEGF seen in tumor-bearing hosts. This study confirmed that, the potent antitumor activity of B.tomentosa extract may be associated with immune modulatory effects by regulating anti-oxidants and cytokine levels. -
Background: The objective of this study was to evaluate the effect of back massage on the anxiety state, cortisol level, systolic/diastolic blood pressure, pulse rate, and sleep quality in family caregivers of patients with cancer. Materials and Methods: Forty-four family caregivers were randomly assigned to either the experimental or control group (22 interventions, 22 controls) after they were matched on age and gender. The intervention consisted of back massage for 15 minutes per day for a week. Main research outcomes were measured at baseline (day I) and follow-up (day 7). Unpaired t-test, paired t test and chi-square test were used to analyse data. Results: The majority of the caregivers were women, married, secondary school educated and housewife. State anxiety (p<0.001), cortisol level (p<0.05), systolic/diastolic blood pressure (p<0.001, p<0.01 respectively), and pulse rate (p<0.01) were significantly decreased, and sleep quality (p<0.001) increased after back massage intervention. Conclusions: The study results show that family caregivers for patients with cancer can benefit from back massage to improve state anxiety, cortisol level, blood pressure and heart rate, and sleep quality. Oncology nurses can take advantage of back massage, which is non-pharmacologic and easily implemented method, as an independent nursing action to support caregivers for patients with cancer.
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Yaacob, Nik Soriani;Kamal, Nik Nursyazni Nik Mohamed;Wong, Kah Keng;Norazmi, Mohd Nor 8135
Background: Cell cycle regulatory proteins are suitable targets for cancer therapeutic development since genetic alterations in many cancers also affect the functions of these molecules. Strobilanthes crispus (S. crispus) is traditionally known for its potential benefits in treating various ailments. We recently reported that an active sub-fraction of S. crispus leaves (SCS) caused caspase-dependent apoptosis of human breast cancer MCF-7 and MDA-MB-231 cells. Materials and Methods: Considering the ability of SCS to also promote the activity of the antiestrogen, tamoxifen, we further examined the effect of SCS in modulating cell cycle progression and related proteins in MCF-7 and MDA-MB-231 cells alone and in combination with tamoxifen. Expression of cell cycle-related transcripts was analysed based on a previous microarray dataset. Results: SCS significantly caused G1 arrest of both types of cells, similar to tamoxifen and this was associated with modulation of cyclin D1, p21 and p53. In combination with tamoxifen, the anticancer effects involved downregulation of$ER{\alpha}$ protein in MCF-7 cells but appeared independent of an ER-mediated mechanism in MDA-MB-231 cells. Microarray data analysis confirmed the clinical relevance of the proteins studied. Conclusions: The current data suggest that SCS growth inhibitory effects are similar to that of the antiestrogen, tamoxifen, further supporting the previously demonstrated cytotoxic and apoptotic actions of both agents. -
Talaeezadeh, Abdolhasan;Bahadoram, Mohammad;Abtahian, Amin;Rezaee, Alireza 8141
Background: to evaluate the outcome of stapled colo-anal anastomoses after extended low anterior resection for distal rectal carcinoma. Materials and Methods: A retrospective study of fifty patients who underwent coloanal anastomoses after extended low anterior resection was conducted at Imam Hospital from September 2007 up to July 2012. Results: The distance of the tumor from anal verge was 3 to 8 cm. Anastomotic leakage developed in 6% of patients and defecation problems in 16%. One-year local recurrence was 6% while three-year local recurrence was 4%. One-year systemic recurrence was seen in 22% while three-year systemic recurrence was seen in 20%. Conclusions: Colo-anal anastomoses after extended low anterior resection for distal rectal carcinoma can be conducted safely. -
Nishimura, Mai;Miyatake, Takashi;Nakashima, Ayaka;Miyoshi, Ai;Mimura, Mayuko;Nagamatsu, Masaaki;Ogita, Kazuhide;Yokoi, Takeshi 8145
Background: Atypical squamous cells of undetermined significance (ASCUS) feature a wide variety of cervical cells, including benign and malignant examples. The management of ASCUS is complicated. Guidelines for office gynecology in Japan recommend performing a high-risk human papillomavirus (HPV) test as a rule. The guidelines also recommend repeat cervical cytology after 6 and 12 months, or immediate colposcopy. The purpose of this study was to determine the clinical significance of ASCUS. Materials and Methods: Between January 2012 and December 2014, a total of 162 patients underwent cervical conization for cervical intraepithelial neoplasia grade 3 (CIN3), carcinoma in situ, squamous cell carcinoma, microinvasive squamous cell carcinoma, and adenocarcinoma in situ at our hospital. The results of cervical cytology prior to conization, the pathology after conization, and high-risk HPV testing were obtained from clinical records and analyzed retrospectively. Results: Based on cervical cytology, 31 (19.1%) of 162 patients were primarily diagnosed with ASCUS. Among these, 25 (80.6%) were positive for high-risk HPV, and the test results of the remaining 6 patients (19.4%) were uncertain. In the final pathological diagnosis after conization, 27 (87.1%) and 4 patients (12.9%) were diagnosed with CIN3 and carcinoma in situ, respectively. Conclusions: Although ASCUS is known as a low-risk abnormal cervical cytology, approximately 20% of patients who underwent cervical conization had ASCUS. The relationship between the cervical cytology of ASCUS and the final pathological results for CIN3 or invasive carcinoma should be investigated statistically. In cases of ASCUS, we recommend HPV tests or colposcopic examination rather than cytological follow-up, because of the risk of missing CIN3 or more advanced disease. -
Bekmukhambetov, Yerbol;Mamyrbayev, Arstan;Jarkenov, Timur;Makenova, Aliya;Imangazina, Zina 8149
An oncopathological state assessment was conducted among adults, children and teenagers in Aktobe region for 2004-2013. Overall the burden of mortality was in the range of 94.8-100.2 per 100,000 population, without any obvious trend over time. Ranking by pathology, the highest incidences among women were registered for breast cancer (5.8-8.4), cervix uteri (2.9-4.6), ovary (2.4-3.6) and corpus uteri, stomach, esophagus, without any marked change over time except for a slight rise in cervical cancer rates. In males, the first place in rank was trachea, bronchus and lung, followed by stomach and esophagus, which are followed by bladder, lymphoid and hematopoietic tissues pathology. Agian no clear trends were apparent over time. In children, main localizations in cancer incidence blood (acute lymphocytic leukemia, lymphosarcoma, acute myeloid leukemia, Hodgkin's disease), brain and central nervous system, bones and articular cartilages, kidneys, and eye and it's appendages, in both sexes. Similarly, in young adults, the major percentage was in blood and lymphatic tissues (acute myeloid leukemia, acute lymphocytic leukemia, Hodgkin's disease) a significant percentage accruing to lymphosarcoma, lymphoma, other myeloid leukemia and hematological malignancies as well as tumors of brain and central nervous system, bones and articular cartilages. This initial survey provides the basis for more detailed investigation of cancer epidemiology in Aktobe, Kazakhstan. -
Gundog, Mete;Yildiz, Oguz G;Imamoglu, Nalan;Aslan, Dicle;Aytekin, Aynur;Soyuer, Isin;Soyuer, Serdar 8155
The prognostic significance of AgNOR proteins in stage II-III rectal cancers treated with chemoradiotherapy was evaluated. Silver staining was applied to the$3{\mu}m$ sections of parafin blocked tissues from 30 rectal cancer patients who received 5-FU based chemoradiotherapy from May 2003 to June 2006. The microscopic displays of the cells were transferred into the computer via a video camera. AgNOR area (nucleolus organizer region area) and nucleus area values were determined as a nucleolus organizer regions area/total nucleus area (NORa/TNa). The mean NORa/TNa value was found to be$9.02{\pm}3.68$ . The overall survival and disease free survival in the high NORa/TNa (>9.02) patients were 52.2 months and 39.4 months respectively, as compared to 100.7 months and 98.4 months in the low NORa/TNa (<9.02) cases. (p<0.001 and p<0.001 respectively). In addition, the prognosis in the high NORa/TNa patients was worse than low NORa/TNa patients (p<0.05). In terms of overall survival and disease-free survival, a statistically significant negative correlation was found with the value of NORa/TNa in the correlations tests. Cox regression analyses demostrated that overall survival and disease-free survival were associated with lymph node status (negative or positive) and the NORa/TNa value. We suggest that two-dimensional AgNOR evaluation may be a safe and usable parameter for prognosis and an indicator of cell proliferation instead of AgNOR dots. -
Paul, Shatabdi;Solanki, Prem Prakash;Shahi, Uday Pratap;Srikrishna, Saripella 8163
Background: Breast cancer is the second most cause of death (1.38 million, 10.9% of all cancer) worldwide after lung cancer. In present study, we assess the knowledge, level of awareness of risk factors and screening practices especially breast self examination (BSE) among women, considering the non-feasibility of diagnostic tools such as mammography for breast screening techniques of breast cancer in the holy city Varanasi, Uttar Pradesh, India. Materials and Methods: A cross-sectional population based survey was conducted. The investigation tool adopted was self administrated questionnaire format. Data were analysed using SPSS 20 version and Chi square test to determine significant association between various education groups with awareness and knowledge, analysis of variance was applied in order to establish significance. Results: The attitude of participants in this study, among 560 women 500 (89%) responded (age group 18-65 years), 53.8% were married. The knowledge about BSE was very low (16%) and out of them 15.6% were practised BSE only once in life time. study shown that prominent age at which women achieve their parity was 20 yrs, among 500 participants 224 women have achieved their parity from age 18 to 30 yrs. Very well known awareness about risk factors of breast cancer were alcohol (64.6%), smoking (64%) and least known awareness risk factors were early menarche (17.2%) and use of red meat (23%). The recovery factors of breast cancer cases were doctors support (95%) and family support (94.5%) as most familiar responses of the holy city Varanasi. Conclusions: The study revealed that the awareness about risk factors and practised of BSE among women in Varanasi is extremely low in comparison with other cities and countries as well (Delhi, Mumbai, Himachal Pradesh, Turkey and Nigeria). However, doctors and health workers may promote the early diagnosis of breast cancer. -
Sharma, Dibyendu;Kannan, Ravi;Tapkire, Ritesh;Nath, Soumitra 8173
Cancer patients frequently experience malnutrition. Cancer and cancer therapy effects nutritional status through alterations in the metabolic system and reduction in food intake. In the present study, fifty seven cancer patients were selected as subjects from the oncology ward of Cachar Cancer Hospital and Research Centre, Silchar, India. Evaluation of nutritional status of cancer patients during treatment was carried out by scored Patient-Generated Subjective Global Assessment (PG-SGA). The findings of PG-SGA showed that 15.8% (9) were well nourished, 31.6% (18) were moderately or suspected of being malnourished and 52.6% (30) were severely malnourished. The prevalence of malnutrition was highest in lip/oral (33.33%) cancer patients. The study showed that the prevalence of malnutrition (84.2%) was high in cancer patients during treatment. -
Khanra, Kalyani;Chakraborty, Anindita;Bhattacharyya, Nandan 8177
The present study was aimed at determining the effects of alkylating and oxidative stress inducing agents on a newly identified variant of DNA polymerase beta ($pol{\beta}{\Delta}_{208-304}$ ) specific for ovarian cancer.$Pol{\beta}{\Delta}_{208-304}$ has a deletion of exons 11-13 which lie in the catalytic part of enzyme. We compared the effect of these chemicals on HeLa cells and HeLa cells stably transfected with this variant cloned into in pcDNAI/neo vector by MTT, colony forming and apoptosis assays.$Pol{\beta}{\Delta}_{208-304}$ cells exhibited greater sensitivity to an alkylating agent and less sensitivity towards$H_2O_2$ and UV when compared with HeLa cells alone. It has been shown that cell death in$Pol{\beta}{\Delta}_{208-304}$ transfected HeLa cells is mediated by the caspase 9 cascade. Exon 11 has nucleotidyl selection activity, while exons 12 and 13 have dNTP selection activity. Hence deletion of this part may affect polymerizing activity although single strand binding and double strand binding activity may remain same. The lack of this part may adversely affect catalytic activity of DNA polymerase beta so that the variant may act as a dominant negative mutant. This would represent clinical significance if translated into a clinical setting because resistance to radiation or chemotherapy during the relapse of the disease could be potentially overcome by this approach. -
Baskaran, Krishnan;Kumar, P Kranthi;Karunanithi, Santha;Sethupathy, Subramanian;Thamaraiselvi, B;Swaruparani, S 8187
Human papillomaviruses (HPVs) are small, non-enveloped, double-stranded DNA viruses that infect epithelial tissues. Specific genotypes of human papillomavirus are the single most common etiological agents of cervical intraepithelial lesions and cervical cancer. Cervical cancer usually arises at squamous metaplastic epithelium of transformation zone (TZ) of the cervix featuring infection with one or more oncogenic or high-risk HPV (HR-HPV) types. A hospital-based study in a rural set up was carried out to understand the association of HR-HPV with squamous intraepithelial lesions (SILs) and cervical cancer. In the present study, HR-HPV was detected in 65.7% of low-grade squamous intraepithelial lesions (LSILs), 84.6% of high-grade squamous intraepithelial lesions (HSILs) and 94% of cervical cancer as compared to 10.7% of controls. The association of HPV infection with SIL and cervical cancer was analyzed with Chi square test (p<0.001). The significant association found confirmed that detection of HR-HPV is a suitable candidate for early identification of cervical precancerous lesions and in the prevention of cervical cancer in India. -
Gudala, Suresh;Khan, Uzma;Kanungo, Niteesh;Bandaru, Srinivas;Hussain, Tajamul;Parihar, MS;Nayarisseri, Anuraj;Mundluru, Hema Prasad 8191
Inhibition of EGFR-EGF interactions forms an important therapeutic rationale in treatment of non-small cell lung carcinoma. Established inhibitors have been successful in reducing proliferative processes observed in NSCLC, however patients suffer serious side effects. Considering the narrow therapeutic window of present EGFR inhibitors, the present study centred on identifying high efficacy EGFR inhibitors through structure based virtual screening strategies. Established inhibitors - Afatinib, Dacomitinib, Erlotinib, Lapatinib, Rociletinib formed parent compounds to retrieve similar compounds by linear fingerprint based tanimoto search with a threshold of 90%. The compounds (parents and respective similars) were docked at the EGF binding cleft of EGFR. Patch dock supervised protein-protein interactions were established between EGF and ligand (query and similar) bound and free states of EGFR. Compounds ADS103317, AKOS024836912, AGN-PC-0MXVWT, GNF-Pf-3539, SCHEMBL15205939 were retrieved respectively similar to Afatinib, Dacomitinib, Erlotinib, Lapatinib, Rociletinib. Compound-AGN-PC-0MXVWT akin to Erlotinib showed highest affinity against EGFR amongst all the compounds (parent and similar) assessed in the study. Further, AGN-PC-0MXVWT brought about significant blocking of EGFR-EGF interactions in addition showed appreciable ADMET properties and pharmacophoric features. In the study, we report AGN-PC-0MXVWT to be an efficient and high efficacy inhibitor of EGFR-EGF interactions identified through computational approaches. -
Malak, Camelia A Abdel;Elghanam, Doaa M;Elbossaty, Walaa Fikry 8197
Background: To investigate the expression of the fragile histidine triad (FHIT) gene in acute lymphoblastic leukemia and its clinical significance. Materials and Methods: The level of expressed FHIT mRNA in peripheral blood from 50 patients with acute lymphoblastic leukemia (ALL) and in 50 peripheral blood samples from healthy volunteers was measured via RT-PCR. Correlation analyses between FHIT gene expression and clinical characteristics (gender, age, white blood count, immunophenotype of acute lymphoblastic leukemia and percentage of blast cells) of the patients were performed. Results: The FHIT gene was expressed at$2.49{\pm}7.37$ of ALL patients against$14.4{\pm}17.9$ in the healthy volunteers. The difference in the expression levels between ALL patients and healthy volunteers was statistically significant. The rate of gene expression did not significantly vary with immunophenotype subtypes. Gene expression was also found to be correlated with increase of total leukocyte and decrease in platelets, but not with age, gender, immunophenotyping or percentage of blast cells. Conclusions: FHIT gene expression is low in acute lymphoblastic leukemia and could be a useful marker to monitor minimal residual disease. This gene is also a candidate target for the immunotherapy of acute lymphoblastic leukemia. -
Bulut, Gulay;Kosem, Mustafa;Bulut, Mehmet Deniz;Erten, Remzi;Bayram, Irfan 8203
Adenocarcinomas (AC) are the most frequently encountered carcinomas. It may be quite challenging to detect the primary origin when those carcinomas metastasize and the first finding is a metastatic tumor. This study evaluated the role of sex hormone binding globulin (SHBG) positivity in tumor cells in the subclassification and detection of the original organ of adenocarcinomas. Between 1994 and 2008, 64 sections of normal tissue belonging to ten organs, and 116 cases diagnosed as adenoid cystic carcinoma and mucoepidermoid carcinoma of the salivary gland, lung adenocarcinoma, invasive ductal carcinoma of the breast, adenocarcinoma of stomach, colon, gallbladder, pancreas and prostate, endometrial adenocarcinoma and serous adenocarcinoma and mucinous adenocarcinoma of the ovary, were sent to the laboratory at the Department of Pathology at the Yuzuncu Yil University School of Medicine, where they were stained immunohistochemically, using antibodies against SHBG. The SHBG immunoreactivity in both the tumor cells and normal cells, together with the type, diffuseness and intensity of the staining were then evaluated. In the differential diagnosis of the adenocarcinomas of the organs, including the glandular structures, impressively valuable results are encountered in the tumor cells, whether the SHBG immunopositivity is evaluated alone or together with other IHC markers. Further extensive research with a larger number of cases, including instances of cholangiocarcinoma and cervix uteri AC [which we could not include in the study for technical reasons] should be performed, in order to appropriately evaluate the role of SHBG in the differential diagnosis of AC. -
Gorbanzadeh, Behrang;Rahmani, Azad;Mogadassian, Sima;Behshid, Mojhgan;Azadi, Arman;Taghavy, Saied 8211
Background: Having a conscience is one of the main pre-requisite of providing nursing care. The knowledge regarding levels of conscience among nurses in eastern countries is limited. So, the purpose of this study was to examine the level of conscience and its related factors among Iranian oncology nurses. Materials and Methods: This descriptive-correlational study was conducted in 3 hospitals in Tabriz, Iran. Overall, 68 nurses were selected using a non-probability sampling method. The perceptions of conscience questionnaire was used to identify the levels of conscience among nurses. The data were analyzed using SPSS version 13.0. Results: The mean nurses' level of conscience scores was 72.7. In the authority and asset sub-scales nurses acquired higher scores. The mean of nurses' scores in burden and depending on culture sub-scales were the least. Also, there were no statistical relationship between some demographic characteristics of participants and their total score on the perceptions of conscience questionnaire. Conclusions: According to study findings Iranian nurses had high levels of conscience. However, understanding all the factors that affect nurses' perception of conscience requires further studies. -
Mohtasham, Nooshin;Saghravanian, Nasrollah;Goli, Maryam;Kadeh, Hamideh 8215
Background: The prevalence of non-squamous cell malignant tumors of the oral cavity has not been evaluated in Iran extensively. The aim of this study was to evaluate epidemiological aspects of the oral malignancies with non-squamous cell origin during a 43-year period in the Faculty of Dentistry, Mashhad University of Medical Sciences, Iran. Materials and Methods: In this retrospective study, the records of all patients referred to dental school of Mashhad university of medical sciences in northeast of Iran, during the period 1971-2013 were evaluated. All confirmed samples of oral non squamous cell malignant tumors were included in this study. Demographic information including age, gender and location of the lesions were extracted from patient's records. Data were analyzed using SPSS statistical soft ware, Chi-square and Fisher's exact tests. Results: Among 11,126 patients, 188 (1.68%) non squamous cell malignant tumors were found, with mean age of 39.9 years ranging from 2 to 92 years. The most common tumors were mucoepidermoid carcinoma (33 cases) and lymphoma (32 cases). Non squamous cell malignant tumors occurred almost equally in men (94 cases) and women (93 cases). Most (134 cases) of them were located peripherally with high frequency in salivary glands (89 cases) and 52 cases were centrally with high frequency in the mandible (38 cases). Conclusions: More findings in this survey were similar to those reported from other studies with differences in some cases; it may be due to variation in the sample size, geographic and racial differences in tumors. -
Moradzadeh, Rahmatollah;Mansournia, Mohammad Ali;Baghfalaki, Taban;Ghiasvand, Reza;Noori-Daloii, Mohammad Reza;Holakouie-Naieni, Kourosh 8221
Background: Misreporting self-reported family history may lead to biased estimations. We used Bayesian methods to adjust for exposure misclassification. Materials and Methods: A hospital-based case-control study was used to identify breast cancer risk factors among Iranian women. Three models were jointly considered; an outcome, an exposure and a measurement model. All models were fitted using Bayesian methods, run to achieve convergence. Results: Bayesian analysis in the model without misclassification showed that the odds ratios for the relationship between breast cancer and a family history in different prior distributions were 2.98 (95% CRI: 2.41, 3.71), 2.57 (95% CRI: 1.95, 3.41) and 2.53 (95% CRI: 1.93, 3.31). In the misclassified model, adjusted odds ratios for misclassification in the different situations were 2.64 (95% CRI: 2.02, 3.47), 2.64 (95% CRI: 2.02, 3.46), 1.60 (95% CRI: 1.07, 2.38), 1.61 (95% CRI: 1.07, 2.40), 1.57 (95% CRI: 1.05, 2.35), 1.58 (95% CRI: 1.06, 2.34) and 1.57 (95% CRI: 1.06, 2.33). Conclusions: It was concluded that self-reported family history may be misclassified in different scenarios. Due to the lack of validation studies in Iran, more attention to this matter in future research is suggested, especially while obtaining results in accordance with sensitivity and specificity values. -
Saikia, Snigdha;Barooah, Prajjalendra;Bhattacharyya, Mallika;Deka, Manab;Goswami, Bhabadev;Sarma, Manash P;Medhi, Subhash 8227
Background: To investigate polymorphisms in heat shock proteins A1B and A1L (HOM) and associated risk of oesophageal carcinoma in Northeast India. Materials and Methods: The study includes oesophageal cancer (ECA) patients attending general outpatient department (OPD) and endoscopic unit of Gauhati Medical College. Patients were diagnosed based on endoscopic and histopathological findings. Genomic DNA was typed for HSPA1B1267 and HSPA1L2437 SNPs using the polymerase chain reaction with restriction fragment length polymorphisms. Results: A total of 78 cases and 100 age-sex matched healthy controls were included in the study with a male: female ratio of 5:3 and a mean age of$61.4{\pm}8.5years$ . Clinico-pathological evaluation showed 84% had squamous cell carcinoma and 16% were adenocarcinoma. Dysphagia grades 4 (43.5%) and 5 (37.1%) were observed by endoscopic and hispathological evaluation. The frequency of genomic variation of A1B from wild type A/A to heterozygous A/G and mutant G/G showed a positive association [chi sq=19.9, p=<0.05] and the allelic frequency also showed a significant correlation [chi sq=10.3, with cases vs. controls, OR=0.32,$p{\leq}0.05$ ]. The genomic variation of A1L from wild T/T to heterozygous T/C and mutant C/C were found positively associated [chi sq=7.02, p<0.05] with development of ECA. While analyzing the allelic frequency, there was no significant association [chi sq=3.19, OR=0.49, p=0.07]. Among all the risk factors, betel quid [OR=9.79, Chi square=35.0, p<0.05], tobacco [OR=2.95, chi square=10.6, p<0.05], smoking [OR=3.23, chi square=10.1, p<0.05] demonstrated significant differences between consumers vs. non consumers regarding EC development. Alcohol did not show any significant association [OR=1.34, chi square=0.69, p=0.4] independently. Conclusions: It can be concluded that the present study provides marked evidence that polymorphisms of HSP70 A1B and HSP70 A1L genes are associated with the development of ECA in a population in Northeast India, A1B having a stronger influence. Betel quid consumption was found to be a highly significant risk factor, followed by smoking and tobacco chewing. Although alcohol was not a potent risk factor independently, alcohol consumption along with tobacco, smoking and betel nut was found to contribute to development of ECA. -
Background: Lung cancer is one of the most common types of cancer causing high morbidity and mortality worldwide. An increasing incidence of lung cancer has been observed in India. Objectives:To evaluate the clinicpathological profile and haematological abnormalities associated with lung cancer in Bangalore, India. Materials and Methods: This prospective study was carried out over a period of 2 years. A total of 96 newly diagnosed and histopathologically confirmed cases of lung cancer were included in the study. Results: Our lung cancer cases had a male to female ratio of 3:1. Distribution of age varied from 40 to 90 years, with a major contribution in the age group between 61 and 80 years (55.2%). Smoking was the commonest risk factor found in 69.7% of patients. The most frequent symptom was cough (86.4%) followed by loss of weight and appetite (65.6%) and dyspnea (64.5%). The most common radiological presentation was a mass lesion (55%). The most common histopathological type was squamous cell carcinoma (47.9%), followed by adenocarcinoma (28.1%) and small cell carcinoma (12.5%). Distant metastasis at presentation was seen in 53.1% patients. Among the haematological abnormalities, anaemia was seen in 61.4% of patients, leucocytosis in 36.4%, thrombocytosis in 14.5% and eosinophilia in 19.7% of patients. Haematological abnormalities were more commonly seen in non small cell lung cancer. Conclusions: Squamous cell carcinoma was found to be the most common histopathological type and smoking still remains the major risk factor for lung cancer. Haematological abnormalities are frequently observed in lung cancer patients, anaemia being the commonest of all.
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Kajitani, Koji;Ken-Ichi, Honda;Terada, Hiroyuki;Yasui, Tomoyo;Sumi, Toshiyuki;Koyama, Masayasu;Ishiko, Osamu 8239
The p53 gene is inactivated by the human papillomavirus (HPV) E6 protein in the majority of cervical cancers. Treatment of HeLa S3 cells with siRNA for HPV E6 permitted adenovirus-mediated transduction of a p53 gene linked to an upstream estrogen response element (ERE). Our previous study in non-siRNA treated HHUA cells, which are derived from an endometrial cancer and express estrogen receptor${\beta}$ , showed enhancing effects of an upstream ERE on adenovirus-mediated p53 gene transduction. In HeLa S3 cells treated with siRNA for HPV E6, adenovirus-mediated transduction was enhanced by an upstream ERE linked to a p53 gene carrying a proline variant at codon 72, but not for a p53 gene with arginine variant at codon 72. Expression levels of p53 mRNA and Coxsackie/adenovirus receptor (CAR) mRNA after adenovirus-mediated transfer of an ERE-linked p53 gene (proline variant at codon 72) were higher compared with those after non-ERE-linked p53 gene transfer in siRNA-treated HeLa S3 cells. Western blot analysis showed lower${\beta}$ -tubulin levels and comparatively higher p53/${\beta}$ -tubulin or CAR/${\beta}$ -tubulin ratios in siRNA-treated HeLa S3 cells after adenovirus-mediated ERE-linked p53 gene (proline variant at codon 72) transfer compared with those in non-siRNA-treated cells. Apoptosis, as measured by annexin V binding, was higher after adenovirus-mediated ERE-linked p53 gene (proline variant at codon 72) transfer compared with that after non-ERE-linked p53 gene transfer in siRNA-treated cells. -
Mokarram, Pooneh;Shakiba-Jam, Fatemeh;Kavousipour, Soudabeh;Sarabi, Mostafa Moradi;Seghatoleslam, Atefeh 8247
Background: The ubiquitin-proteasome system (UPS) degrades a variety of proteins which attach to specific signals. The ubiquitination pathway facilitates degradation of damaged proteins and regulates growth and stress responses. This pathway is altered in various cancers, including acute lymphoblastic leukemia, head and neck squamous cell carcinoma and breast cancer. Recently it has been reported that expression of newly characterized human genes, UBE2Q1 and UBE2Q2, putative members of ubiquitin-conjugating enzyme family (E2), has been also changed in colorectal cancer. Epigenetics is one of the fastest-growing areas of science and nowadays has become a central issue in biological studies of diseases. According to the lack of information about the role of epigenetic changes on gene expression profiling of UBE2Q1 and UBE2Q2, and the presence of CpG islands in the promoter of these two human genes, we decided to evaluate the promoter methylation status of these genes as a first step. Materials and Methods: The promoter methylation status of UBE2Q1 and UBE2Q2 was studied by methylation-specific PCR (MSP) in tumor samples of 60 colorectal cancer patients compared to adjacent normal tissues and 20 non-malignant controls. The frequency of the methylation for each gene was analyzed by chi-square method. Results: MSP results revealed that UBE2Q2 gene promoter were more unmethylated, while a higher level of methylated allele was observed for UBE2Q1 in tumor tissues compared to the adjacent normal tissues and the non malignant controls. Conclusions: UBE2Q1 and UBE2Q2 genes show different methylation profiles in CRC cases. -
Takemoto, Shigeki;Iwanaga, Masako;Sagara, Yasuko;Watanabe, Toshiki 8253
Elevated levels of soluble CD30 (sCD30) are linked with various T-cell neoplasms. However, the relationship between sCD30 levels and the development of adult T-cell leukemia (ATL) in human T-cell leukemia virus type 1 (HTLV-1) carriers remains to be clarified. We here investigated whether plasma sCD30 is associated with risk of ATL in a nested case-control study within a cohort of HTLV-1 carriers. We compared sCD30 levels between 11 cases (i.e., HTLV-1 carriers who later progressed to ATL) and 22 age-, sex- and institution-matched control HTLV-1 carriers (i.e., those with no progression). The sCD30 concentration at baseline was significantly higher in cases than in controls (median 65.8, range 27.2-134.5 U/mL vs. median 22.2, range 8.4-63.1 U/mL, P=0.001). In the univariate logistic regression analysis, a higher sCD30 (${\geq}30.2U/mL$ ) was significantly associated with ATL development (odds ratio 7.88 and the 95% confidence intervals 1.35-45.8, P = 0.02). Among cases, sCD30 concentration tended to increase at the time of diagnosis of aggressive-type ATL, but the concentration was stable in those developing the smoldering-type. This suggests that sCD30 may serve as a predictive marker for the onset of aggressive-type ATL in HTLV-1 carriers. -
Mohammadian, Farideh;Abhari, Alireza;Dariushnejad, Hassan;Zarghami, Faraz;Nikanfar, Alireza;Pilehvar-Soltanahmadi, Yones;Zarghami, Nosratollah 8259
Background: Nano-therapy has the potential to revolutionize cancer therapy. Chrysin, a natural flavonoid, was recently recognized as having important biological roles in chemical defenses and nitrogen fixation, with anti-inflammatory and anti-oxidant effects but the poor water solubility of flavonoids limitstheir bioavailability and biomedical applications. Objective: Chrysin loaded PLGA-PEG-PLGA was assessed for improvement of solubility, drug tolerance and adverse effects and accumulation in a gastric cancer cell line (AGS). Materials and Methods: Chrysin loaded PLGA-PEG copolymers were prepared using the double emulsion method (W/O/W). The morphology and size distributions of the prepared PLGA-PEG nanospheres were investigated by 1H NMR, FT-IR and SEM. The in vitro cytotoxicity of pure and nano-chrysin was tested by MTT assay and miR-34a was measured by real-time PCR. Results: 1H NMR, FT-IR and SEM confirmed the PLGA-PEG structure and chrysin loaded on nanoparticles. The MTT results for different concentrations of chrysin at different times for the treatment of AGS cell line showed IC50 values of 68.2, 56.2 and$42.3{\mu}M$ and 58.2, 44.2,$36.8{\mu}M$ after 24, 48, and 72 hours of treatment, respectively for chrysin itslef and chrysin-loaded nanoparticles. The results of real time PCR showed that expression of miR-34a was upregulated to a greater extent via nano chrysin rather than free chrysin. Conclusions: Our study demonstrates chrysin loaded PLGA-PEG promises a natural and efficient system for anticancer drug delivery to fight gastric cancer. -
Hatam, Nahid;Askarian, Mehrdad;Javan-Noghabi, Javad;Ahmadloo, Niloofar;Mohammadianpanah, Mohammad 8265
Purpose: A cost-utility analysis was performed to assess the cost-utility of neoadjuvant chemotherapy regimens containing doxorubicin and cyclophosphamide (AC) versus paclitaxel and gemcitabine (PG) for locally advanced breast cancer patients in Iran. Materials and Methods: This cross-sectional study in Namazi hospital in Shiraz, in the south of Iran covered 64 breast cancer patients. According to the random numbers, the patients were divided into two groups, 32 receiving AC and 32 PG. Costs were identified and measured from a community perspective. These items included medical and non-medical direct and indirect costs. In this study, a data collection form was used. To assess the utility of the two regimens, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core30 (EORTC QLQ-C30) was applied. Using a decision tree, we calculated the expected costs and quality adjusted life years (QALYs) for both methods; also, the incremental cost-effectiveness ratio was assessed. Results: The results of the decision tree showed that in the AC arm, the expected cost was 39,170 US$ and the expected QALY was 3.39 and in the PG arm, the expected cost was 43,336 dollars and the expected QALY was 2.64. Sensitivity analysis showed the cost effectiveness of the AC and ICER=-5535 US$. Conclusions: Overall, the results showed that AC to be superior to PG in treatment of patients with breast cancer, being less costly and more effective. -
Tork, Ola M;Khaleel, Eman F;Abdelmaqsoud, Omnia M 8271
Background: Hepato-carcinogenesis is multifaceted in its molecular aspects. Among the interplaying agents are altered gap junctions, the proteasome/autophagy system, and mitochondria. The present experimental study was designed to outline the roles of these players and to investigate the tumor suppressive effects of curcumin with or without mesenchymal stem cells (MSCs) in hepatocellular carcinoma (HCC). Materials and Methods: Adult female albino rats were divided into normal controls and animals with HCC induced by diethyl-nitrosamine (DENA) and$CCl_4$ . Additional groups treated after HCC induction were: Cur/HCC which received curcumin; MSCs/HCC which received MSCs; and Cur+MSCs/HCC which received both curcumin and MSCs. For all groups there were histopathological examination and assessment of gene expression of connexin43 (Cx43), ubiquitin ligase-E3 (UCP-3), the autophagy marker LC3 and coenzyme-Q10 (Mito.Q10) mRNA by real time, reverse transcription-polymerase chain reaction, along with measurement of LC3II/LC3I ratio for estimation of autophagosome formation in the rat liver tissue. In addition, the serum levels of ALT, AST and alpha fetoprotein (AFP), together with the proinflammatory cytokines$TNF{\alpha}$ and IL-6, were determined in all groups. Results: Histopathological examination of liver tissue from animals which received DENA-$CCl_4$ only revealed the presence of anaplastic carcinoma cells and macro-regenerative nodules. Administration of curcumin, MSCs; each alone or combined into rats after induction of HCC improved the histopathological picture. This was accompanied by significant reduction in${\alpha}$ -fetoprotein together with proinflammatory cytokines and significant decrease of various liver enzymes, in addition to upregulation of Cx43, UCP-3, LC3 and Mito.Q10 mRNA. Conclusions: Improvement of Cx43 expression, nonapoptotic cell death and mitochondrial function can repress tumor growth in HCC. Administration of curcumin and/or MSCs have tumor suppressive effects as they can target these mechanisms. However, further research is still needed to verify their effectiveness. -
Tongtawee, Taweesak;Dechsukhum, Chavaboon;Matrakool, Likit;Panpimanmas, Sukij;Loyd, Ryan A;Kaewpitoon, Soraya J;Kaewpitoon, Natthawut 8281
Background: Helicobacter pylori is a cause of chronic gastritis, peptic ulcer disease, and gastric malignancy, infection being a serious health problem in Thailand. Recently, clarithromycin resistant H. pylori strains represent the main cause of treatment failure. Therefore this study aimed to determine the prevalence and pattern of H. pylori resistance to clarithromycin in Suranaree University of Technology Hospital, Suranree University of Technology, Nakhon Ratchasima, Northeastern Thailand, Nakhon Ratchasima province, northeast of Thailand. Materials and Methods: This hospital-based cross-sectional study was carried out between June 2014 and February 2015 with 300 infected patients interviewed and from whom gastric mucosa specimens were collected and proven positive by histology. The gastric mucosa specimens were tested for H. pylori and clarithromycin resistance by 23S ribosomal RNA point mutations analysis using real-time polymerase chain reactions. Correlation of eradication rates with patterns of mutation were analyzed by chi-square test. Results: Of 300 infected patients, the majority were aged between 47-61 years (31.6%), female (52.3%), with monthly income between 10,000-15,000 Baht (57%), and had a history of alcohol drinking (59.3%). Patient symptoms were abdominal pain (48.6%), followed by iron deficiency anemia (35.3%). Papaya salad consumption (40.3%) was a possible risk factor for H. pylori infection. The prevalence of H. pylori strains resistant to clarithromycin was 76.2%. Among clarithromycin-resistant strains tested, all were due to the A2144G point mutation in the 23S rRNA gene. Among mutations group, wild type genotype, mutant strain mixed wild type and mutant genotype were 23.8%, 35.7% and 40.5% respectively. With the clarithromycin-based triple therapy regimen, the efficacy decreased by 70% for H. pylori eradication (P<0.01). Conclusions: Recent results indicate a high rate of H. pylori resistance to clarithromycin. Mixed of wild type and mutant genotype is the most common mutant genotype in Nakhon Ratchasima province, therefore the use of clarithromycin-based triple therapy an not advisable as an empiric first-line regimen for H. pylori eradication in northeast region of Thailand. -
Qasem, Wiam Al;Yousef, Al-Motassem;Yousef, Mohammad;Manasreh, Ihab 8287
Background: Thymidylate synthase (TS) catalyzes the methylation of deoxyuridylate to deoxythymidylate and is involved in DNA methylation, synthesis and repair. Two common polymorphisms have been reported, tandem repeats in the promoter-enhancer region (TSER), and 6bp ins/del in the 5'UTR, that are implicated in a number of human diseases, including cancer. The association between the two polymorphisms in risk for lung cancer (LC) was here investigated in the Jordanian population. Materials and Methods: An age, gender, and smoking-matched case-control study involving 84 lung cancer cases and 71 controls was conducted. The polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) technique was used to detect the polymorphism of interest. Results: Individuals bearing the ins/ins genotype were 2.5 times more likely to have lung cancer [(95%CI: 0.98-6.37), p=0.051]. Individuals who were less than or equal to 57 years and carrying ins/ins genotype were 4.6 times more susceptible to lung cancer [OR<57 vs >57years: 4.6 (95%CI: 0.93-22.5), p=0.059)]. Genotypes and alleles of TSER were distributed similarly between cases and controls. Weak linkage disequilibrium existed between the two loci of interest (Lewontin's coefficient [D']) (LC: D' =0.03, r2: 0. 001, p=0.8; Controls: D' =0.29, r2: 0.08, p=0.02). Carriers of the "3 tandem repeats_insertion" haplotype (3R_ins) were 2 times more likely to have lung cancer [2 (95%CI: 1.13-3.48), p=0.061]. Conclusions: Genetic polymorphism of TS at 3 'UTR and its haplotype analysis may modulate the risk of lung cancer in Jordanians. The 6bp ins/del polymorphism of TS at 3 'UTR is more informative than TSER polymorphism in predicting increased risk. -
Desai, Fanny Sharadkumar;Nongthombam, Jitendra;Singh, Lisam Shanjukumar 8293
Background: Urinary stones are known predisposing factors for upper urinary tract carcinoma (UUTC) which are commonly detected at advanced stage with poor outcome because of rarity and lack of specific criteria for early detection. Aims and objectives: The main aim was to evaluate the impact of age, gender andstone characteristics on risk of developing UUTC in patients with chronic nephrolithiasis. We also discuss the role of aberrant angiogenesis (AA) and immunohistochemical expression of p53, p16INK4a, CK20 and Ki-67 in diagnosis of pelvicalyceal neoplastic (NL) and pre-neoplastic lesions (PNL) in these patients. Materials and Methods: Retrospective analysis of pelvicalyceal urothelial lesions from 88 nephrectomy specimens were carried out in a tertiary care centre from June 2012 to December 2014. Immunohistochemistry (IHC) was performed on 37 selected cases. Computed image analysis was performed to analyse aberrant angiogenesis. Results: All UUTC (5.7%) and metaplastic lesions were found to be associated with stones. Some 60% were pure squamous cell carcinoma and 40% were transitional cell carcinoma. Odd ratios for developing NL and PNL lesions in presence of renal stone, impacted stones, multiple and large stag horn stones were 9.39 (95% CI 1.15-76.39, p value 0.05), 6.28 (95% CI 1.59-24.85, p value 0.000) and 7.4 (95% CI, 2.29-23.94, p value 0.001) respectively. When patient age was${\geq}55$ , the odds ratio for developing NL was 3.43 (95% CI 1.19-9.88, p value 0.019). IHC analysis showed that mean Ki-67 indices were$3.15{\pm}3.63%$ for non-neoplastic lesions,$10.0{\pm}9.45%$ for PNL and$28.0{\pm}18.4%$ for NL. Sensitivity and specificity of CK20, p53, p16INK4a, AA were 76% and 95.9%; 100% and 27.5%; 100% and 26.5%; 92.3 % and 78.8% respectively. Conclusions: Age${\geq}55years$ , large stag horn stones, multiple stones and impacted stones are found to be associated with increased risk of NL and PNL in UUT. For flat lesions, a panel of markers, Ki 67 index >10 and presence of aberrant angiogenesis were more useful than individual markers. -
Mahmoud, Enas H;Fawzy, Amal;Ahmad, Omar K;Ali, Amr M 8299
Background: In Egypt, breast cancer is estimated to be the most common cancer among females. It is also a leading cause of cancer-related mortality. Use of circulating cell-free DNA (ccf-DNA) as non-invasive biomarkers is a promising tool for diagnosis and follow-up of breast cancer (BC) patients. Objective: To assess the role of circulating cell free DNA (nuclear and mitochondrial) in diagnosing BC. Materials and Methods: Multiplex real time PCR was used to detect the level of ccf nuclear and mitochondrial DNA in the peripheral blood of 50 breast cancer patients together with 30 patients with benign lesions and 20 healthy controls. Laboratory investigations, histopathological staging and receptor studies were carried out for the cancer group. Receiver operating characteristic curves were used to evaluate the performance of ccf-nDNA and mtDNA. Results: The levels of both nDNA and mtDNA in the cancer group were significantly higher in comparison to the benign and the healthy control group. There was a statistically significant association between nDNA and mtDNA levels and well established prognostic parameters; namely, histological grade, tumour stage, lymph node status andhormonal receptor status. Conclusions: Our data suggests that nuclear and mitochondrial ccf-DNA may be used as non-invasive biomarkers in BC. -
Lung cancer is one particular type of cancer that is deadly and relatively common than any other. Treatment is with chemotherapy, radiation therapy and surgery depending on the type and stage of the disease. Focusing on drugs used for chemotherapy and their associated side effects, there is a need to design and develop new anti-lung cancer drugs with minimal side effects and improved efficacy. The pharmacophore model appears to be a very helpful tool serving in the designing and development of new lead compounds. In this paper, pharmacophore analysis of 10 novel anti-lung cancer compounds was validated for the first time. Using LigandScout the pharmacophore features were predicted and 3D pharmacophores were extracted via VMD software. A training set data was collected from literature and the proposed model was applied to the training set whereby validating and verifying similar activity as that of the most active compounds was achieved. Therefore pharmacophore develoipment could be recommended for further studies.
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Paramasivam, Arumugam;Raghunandhakumar, Subramanian;Priyadharsini, Jayaseelan Vijayashree;Jayaraman, Gopalswamy 8313
We have recently shown that thymoquinone (TQ) has a potent cytotoxic effect and induces apoptosis via caspase-3 activation with down-regulation of XIAP in mouse neuroblastoma (Neuro-2a) cells. Interestingly, our results showed that TQ was significantly more cytotoxic towards Neuro-2a cells when compared with primary normal neuronal cells. In this study, the effects of TQ on cell-cycle regulation and the mechanisms that contribute to this effect were investigated using Neuro-2a cells. Cell-cycle analysis performed by flow cytometry revealed cell-cycle arrest at G2/M phase and a significant increase in the accumulation of TQ-treated cells at sub-G1 phase, indicating induction of apoptosis by the compound. Moreover, TQ increased the expression of p53, p21 mRNA and protein levels, whereas it decreased the protein expression of PCNA, cyclin B1 and Cdc2 in a dose-dependent manner. Our finding suggests that TQ could suppress cell growth and cell survival via arresting the cell-cycle in the G2/M phase and inducing apoptosis of neuroblastoma cells. -
Wairachpanich, Varangkana;Limpongsanurak, Sompop;Lertkhachonsuk, Ruangsak 8321
Background: The incidence of hydatidiform mole (HM) differs among regions but has declined significantly over time. In Thailand, the initiation of universal health coverage in 2002 has resulted in a change of medical services countrywide. However, impacts of these policies on gestational trophoblastic disease (GTD) cases in Thailand have not been reported. This study aimed to find the incidence of hydatidiform mole (HM) in King Chulalongkorn Memorial Hospital (KCMH) from 1994-2013, comparing before and after the implementation of the universal coverage health policy. Materials and Methods: All cases of GTD in KCMH from 1994-2013 were reviewed from medical records. The incidence of HM, patient characteristics, treatment and remission rates were compared over two study decades between 1994-2003 and 2004-2013. Results: Hydatidiform mole cases decreased from 204 cases in the first decade to 111 cases in the seond decade. Overall incidence of HM was 1.70 per 1,000 deliveries. The incidence of HM in the first and second decades were 1.70 and 1.71 per 1,000 deliveries, respectively (p=0.65, 95%CI 1.54-1.88). Referred cases of nonmolar gestational trophoblastic neoplasia (GTN) increased from 12 (4.4%) to 23 (14.4%, p<0.01). Vaginal bleeding was the most common presenting symptom which decreased from 89.4% to 79.6% (p=0.02). Asymptomatic HM patients increased from 4.8% to 10.2% (p=0.07). Rate of postmolar GTN was 26%. Conclusions: The number of HM cases in this study decreased over 2 decades but incidence was unchanged. Referral rates of malignant cases were more common after universal health coverage policy initiation. Classic clinical presentation was decreased significantly in the last decade. -
Lalitwongsa, Somkiat;Pongnikorn, Donsuk;Daoprasert, Karnchana;Sriplung, Hutcha;Bilheem, Surichai 8327
Background: The recent epidemiologic transition in Thailand, with decreasing incidence of infectious diseases along with increasing rates of chronic conditions, including cancer, is a serious problem for the country. Breast cancer has the highest incidence rates among females throughout Thailand. Lampang is a province in the upper part of Northern Thailand. A study was needed to identify the current burden, and the future trends of breast cancer in upper Northern Thai women. Materials and Methods: Here we used cancer incidence data from the Lampang Cancer Registry to characterize and analyze the local incidence of breast cancer. Joinpoint analysis, age period cohort model and Nordpred package were used to investigate the incidences of breast cancer in the province from 1993 to 2012 and to project future trends from 2013 to 2030. Results: Age-standardized incidence rates (world) of breast cancer in the upper parts of Northern Thailand increased from 16.7 to 26.3 cases per 100,000 female population which is equivalent to an annual percentage change of 2.0-2.8%, according to the method used. Linear drift effects played a role in shaping the increase of incidence. The three projection method suggested that incidence rates would continue to increase in the future with incidence for women aged 50 and above, increasing at a higher rate than for women below the age of 50. Conclusions: The current early detection measures increase detection rates of early disease. Preparation of a budget for treatment facilities and human resources, both in surgical and medical oncology, is essential. -
Faeghi, Fariborz;Baniasadipour, Banafsheh;Jalalshokouhi, Jalal 8335
Purpose: To make a comparison of single voxel magnetic resonance spectroscopy (SV-MRS) and dynamic contrast enhancement (DCE) MRI for differentiation of benign and malignant breast lesions in a sample of Iranian women. Materials and Methods: A total of 30 women with abnormal breast lesions detected in mammography, ultrasound, or clinical breast exam were examined with DCE and SV-MRS. tCho (total choline) resonance in MRS spectra was qualitatively evaluated and detection of a visible tCho peak at 3.2 ppm was defined as a positive finding for malignancy. Different types of DCE curves were persistent (type 1), plateau (type 2), and washout (type 3). At first, lesions were classified according to choline findings and types of DCE curve, finally being compared to pathological results as the standard reference. Results: this study included 19 patients with malignant lesions and 11 patients with benign ones. While 63.6 % of benign lesions (7 of 11) showed type 1 DCE curves and 36.4% (4 of 11) showed type 2, 57.9% (11of 19) of malignant lesions were type 3 and 42.1% (8 of 19) type 2. Choline peaks were detected in 18 of 19 malignant lesions and in 3 of 11 benign counterparts. 1 malignant and 8 benign cases did not show any visible resonance at 3.2 ppm so SV-MRS featured 94.7% sensitivity, 72.7 % specificity and 86.7% accuracy.Conclusions: The present findings indicate that a combined approach using MRS and DCE MRI can improve the specificity of MRI for differentiation of benign and malignant breast lesions. -
Masroor, Imrana;Zeeshan, Sana;Afzal, Shaista;Sufian, Saira Naz;Ali, Madeeha;Khan, Shaista;Ahmad, Khabir 8339
Background: To determine the outcome and cost saving by placing ultrasound guided surgical clips for tumor localization in patients undergoing neo-adjuvant chemotherapy for breast cancer. Materials and Methods: This retrospective cross sectional analytical study was conducted at the Department of Diagnostic Radiology, Aga Khan University Hospital, Karachi, Pakistan from January to December 2014. A sample of 25 women fulfilling our selection criteria was taken. All patients came to our department for ultrasound guided core biopsy of suspicious breast lesions and clip placement in the index lesion prior to neo-adjuvant chemotherapy. All the selected patients had biopsy proven breast cancer. Results: The mean age was$45{\pm}11.6years$ . There were no complications seen after clip placement in terms of clip migration or hemorrhage. The cost of commercially available markers was approximately PKR 9,000 (US$ 90) and that of the surgical clip was PKR 900 (US$ 9). The cost of surgical clips in 25 patients was PKR 22,500 (US$ 225), when compared to the commercially available markers which may have incurred a cost of PKR 225,000 (US$ 2,250). The total cost saving for 25 patients was PKR 202,500 (US$ 2, 025), making it PKR 8100 (US$ 81) per patient. Conclusions: The results of our study show that ultrasound guided surgical clip placement in index lesions prior to neo-adjuvant therapy is a safe and cost effective method to identify tumor bed and response to treatment for further management. -
Suan, Mohd Azri Mohd;Mohammed, Noor Syahireen;Hassan, Muhammad Radzi Abu 8345
Background: Although the incidence of colorectal cancer in Malaysia is increasing, awareness of this cancer, including its symptoms, risk factors and screening methods, remains low among Malaysian populations. This survey was conducted with the aim of (i) ascertaining the awareness level regarding colorectal cancer symptoms, risk factors and its screening among the general populations and (ii) assessing the public preference and willingness to pay for colorectal cancer screening. Materials and Methods: The questionnaire was distributed in eight major cities in West Malaysia during the World Health Digestive Day (WDHD) campaign. Two thousand four hundred and eight respondents participated in this survey. Results: Generally, awareness of colorectal cancer was found to be relatively good. Symptoms such as change in bowel habit, blood in the stool, weight loss and abdominal pain were well recognized by 86.6%, 86.9%, 83.4% and 85.6% of the respondents, respectively. However, common risk factors such as positive family history, obesity and old age were acknowledged only by less than 70% of the respondents. Almost 80% of the respondents are willing to take the screening test even without any apparent symptoms. Colonoscopy is the preferred screening method, but only 37.5% were willing to pay from their own pocket to get early colonoscopy. Conclusions: Continous cancer education should be promoted with more involvement from healthcare providers in order to make future colorectal cancer screening programs successful. -
Manjunath, KN;Siddalingaswamy, PC;Prabhu, GK 8351
Electronic cleansing is an image post processing technique in which the tagged colonic content is subtracted from colon using CTC images. There are post processing artefacts, like: 1) soft tissue degradation; 2) incomplete cleansing; 3) misclassification of polyp due to pseudo enhanced voxels; and 4) pseudo soft tissue structures. The objective of the study was to subtract the tagged colonic content without losing the soft tissue structures. This paper proposes a novel adaptive method to solve the first three problems using a multi-step algorithm. It uses a new edge model-based method which involves colon segmentation, priori information of Hounsfield units (HU) of different colonic contents at specific tube voltages, subtracting the tagging materials, restoring the soft tissue structures based on selective HU, removing boundary between air-contrast, and applying a filter to clean minute particles due to improperly tagged endoluminal fluids which appear as noise. The main finding of the study was submerged soft tissue structures were absolutely preserved and the pseudo enhanced intensities were corrected without any artifact. The method was implemented with multithreading for parallel processing in a high performance computer. The technique was applied on a fecal tagged dataset (30 patients) where the tagging agent was not completely removed from colon. The results were then qualitatively validated by radiologists for any image processing artifacts. -
Sangkittipaiboon, Somphob;Leklob, Atit;Sriplung, Hutcha;Bilheem, Surichai 8359
Background: Thailand has come to an epidemiologic transition with decreasing infectious diseases and increasing burden of chronic conditions, including cancer. Breast cancer has the highest incidence rates among females throughout Thailand. This study aimed to identify the current burden and the future trends of breast cancer of Lopburi, a province in the Central Thailand. Materials and Methods: We used cancer incidence data from the Lopburi Cancer Registry to characterize and analyze the incidence of breast cancer in Central Thailand. With joinpoint and age-period-cohort analyses, the incidence of breast cancer in the province from 2001 to 2010 and project future trends from 2011 to 2030 was investigated. Results: Age-adjusted incidence rates of breast cancer in Lopburi increased from 23.4 to 34.3 cases per 100,000 female population during the period, equivalent to an annual percentage change of 4.3% per year. Both period and cohort effects played a role in shaping the increase in incidence. Joinpoint projection suggested that incidence rates would continue to increase in the future with incidence for women ages 50 years and above increasing at a higher rate than for women below the age of 50. Conclusions: The current situation where early detection measures are being promoted could increase detection rates of the disease. Preparation of sufficient budget for treatment facilities and human resources, both in surgical and medical oncology, is essential for future medical care. -
Al-Tayar, Badr Abdullah;Tin-Oo, Mon Mon;Sinor, Modh Zulkarnian;Alakhali, Mohammed Sultan 8365
Background: Shammah is a traditional form of snuff dipping tobacco (a smokeless tobacco form) that is commonly used in Yemen. Oral mucosal changes due to the use of shammah can usually be observed in the mucosal surfaces that the product touches. The aim of this study was to determine the association between shammah use and oral leukoplakia-like lesions. Other associated factors were also determined. Materials and Methods: A cross sectional study was conducted on 346 randomly selected adult males. Multi-stage random sampling was used to select the study location. After completing the structured questionnaire interviews, all the participants underwent clinical exanimation for screening of oral leukoplakia-like lesions Clinical features of oral leukoplakia-like lesion were characterized based on the grades of$Ax{\acute{e}}ll$ et al (1976). Univariable logistic regression and multivariable logistic regression were used to assess the potential associated factors. Results: Out of 346 male participants aged 18 years and older, 68 (19.7%) reported being current shammah users. The multivariable analysis revealed that age, non-formal or primary level of education, former shammah user, current shammah user, and frequency of shammah use per day were statistically associated with the presence of oral leukoplakia-like lesions [Adjusted odds ratio (AOR) = 1.03; 95% confidence interval (CI) : 1.01, 1.06; P=0.006], (AOR=8.65; 95% CI: 2.81, 26.57; P=0.001), (AOR=3.65; 95% CI: 1.40, 9.50; P=0.008), (AOR=12.99; 95% CI: 6.34, 26.59; P=0.001), and (AOR=1.17; 95% CI: 1.02, 1.36; P=0.026), respectively. Conclusions: The results revealed oral leukoplakia-like lesions to be significantly associated with shammah use. Therefore, it is important to develop comprehensive shammah prevention programs in Yemen. -
Taheri-Kharameh, Zahra;Noorizadeh, Farsad;Sangy, Samira;Zamanian, Hadi;Shouri-Bidgoli, Ali Reza;Oveisi, Helaleh 8371
Background: Colorectal cancer is one of the most common neoplasms in Iran. Secondary prevention (colorectal cancer screening) is important and a most valuable method of early diagnosis of this cancer. The objectives of this study were to determine the factors associated with colorectal cancer screening adherence among Iranians 50 years and older using the Health Belief Model. Materials and Methods: This cross-sectional study was conducted from June 2012 to May 2013. A convenience sample of 200 individuals aged 50 and older was recruited from the population at outpatient clinics in teaching hospitals. Data gathering tools were the Champions health belief model scale (CHBMS) with coverage of socio-demographic background and CRC screening information. Multiple logistic regression was performed to identify factors associated with colorectal cancer screening adherence. Results: The mean age of participants was$62.5{\pm}10.8$ and 75.5% were women. A high percentage of the participants had not heard or read about colorectal cancer (86.5%) and CRC screening (93.5%). Perceived susceptibility to colorectal cancer had the lowest percentage of all of the subscales. Participants who perceived more susceptibility (OR =2.99; CI 95%: 1.23-5.45) and reported higher knowledge (OR =1.29; CI 95%: 1.86-3.40) and those who reported fewer barriers (OR =.37; CI 95%:.21-.89), were more likely to have carried out colorectal cancer screening. Conclusions: Our findings indicated that CRC knowledge, perceived susceptibility and barriers were significant predictors of colorectal cancer screening adherence. Strategies to increase knowledge and overcome barriers in risk individuals appear necessary. Education programs should be promoted to overcome knowledge deficiency and negative perceptions in elderly Iranians. -
Khlaiphuengsin, Apichaya;Kiatbumrung, Rattanaporn;Payungporn, Sunchai;Pinjaroen, Nutcha;Tangkijvanich, Pisit 8377
Background: The aim of this study was to evaluate any association between a single nucleotide polymorphism (SNP) in the patatin-like phospholipase domain containing 3 (PNPLA3) (rs738409, C>G) and the development and prognosis in patients with hepatocellular carcinoma (HCC). Materials and Methods: Two hundred heathy controls and 388 HCC cases were included: 211 with HBV, 98 patients with HCV, 29 with alcoholic steatohepatitis (ASH) and 52 with non-alcoholic steatohepatitis (NASH). The SNP was determined by real-time PCR based on TaqMan assays. Results: The prevalence of rs738409 genotypes CC, CG and GG in controls was 91 (45.5%), 88 (44.0%), and 21 (10.5%), respectively, while the corresponding genotypes in all patients with HCC was 158 (40.7%), 178 (45.9%), and 52 (13.4%). The GG genotype had significantly higher distribution in patients with ASH/NASH-related HCC compared with controls (OR=2.34, 95% CI=1.16-4.71, P=0.018), and viral-related HCC cases (OR=2.15, 95% CI=1.13-4.08, P=0.020). However, the frequency of the GG genotype was similar between controls and patients with viral-related HCC. At initial diagnosis, HBV-related HCC were larger and at more advanced BCLC stage than the other HCC groups. There were no significant differences between the GG and non-GG groups regarding clinical characteristics, tumor stage and overall survival. Conclusions: These data suggest an influence of the PNPLA3 polymorphism on the occurrence of HCC in patients with ASH/NASH but not among those with chronic viral hepatitis. However, the polymorphism was not associated with the prognosis of HCC. -
Kharadi, Usama A Rashid;Onkar, Sanjeev;Birangane, Rajendra;Chaudhari, Swapnali;Kulkarni, Abhay;Chaudhari, Rohan 8383
Background: To evaluate the safety, convenience and effectiveness of 940nm diode laser for treatment of homogenous leukoplakia. Materials and Methods: Ten patients having homogenous leukoplakia which were diagnosed clinically were selected from an Indian dental educational institution for the study. Toludine blue staining was applied locally over the lesion. The area where there was increased uptake of stain was excised using a 940 nm EZLASE TM diode laser (BIOLASE-USA). Results: Although various treatment modalities have been tried and the search continues for novel treatment modalities for complete removal of homogenous leukoplakia, from results of our preliminary pilot study it is clear that the use of 940 nm diode laser as a treatment modality for homogenous leukoplakia is a good substitute. Healing was perfect without any complication within a duration of 1 month. Pain intensity was also mild and absolutely zero on the VAS scale after 1 month follow up. Conclusions: 940 nm diode lasers are safe and can be effectively used as a treatment modality of homogenous leukoplakia, without any complication and without compromising health and oral function of patients. Considering recurrence factor, long term follow up for patients is a must. -
Murray, Nigel P;Reyes, Eduardo;Fuentealba, Cynthia;Orellana, Nelson;Jacob, Omar 8387
Background: Treatment of biochemical failure after radical prostatectomy for prostate cancer is largely empirically based. The use of PSA kinetics has been used as a guide to determine local or systemic treatment of biochemical failure. We here compared PSA kinetics with detection of bone marrow micrometastasis as methods to determine local or systemic relapse. Materials and Methods: A transversal study was conducted of men with biochemical failure, defined as a serum PSA >0.2ng/ml after radical prostatectomy. Consecutive patients having undergone radical prostatectomy and with biochemical failure were enrolled and clinical and pathological details were recorded. Bone marrow biopsies were obtained from the iliac crest and touch prints made, micrometastasis (mM) being detected using anti-PSA. The clinical parameters of total serum PSA, PSA velocity, PSA doubling time and time to biochemical failure, age, Gleason score and pathological stage were registered. Results: A total of 147 men, mean age$71.6{\pm}8.2years$ , with a median time to biochemical failure of 5.5 years (IQR 1.0-6.3 years) participated in the study. Bone marrow samples were positive for micrometastasis in 98/147 (67%) of patients at the time of biochemical failure. The results of bone marrow micrometastasis detected by immunocytochemistry were not concordant with local relapse as defined by PSA velocity, time to biochemical failure or Gleason score. In men with a PSA doubling time of < six months or a total serum PSA of >2,5ng/ml at the time of biochemical failure the detection of bone marrow micrometastasis was significantly higher. Conclusions: The detection of bone marrow micrometastasis could be useful in defining systemic relapse, this minimally invasive procedure warranting further studies with a larger group of patients. -
Kaewpitoon, Soraya J;Namwichaisirikul, Niwatchai;Loyd, Ryan A;Churproong, Seekaow;Ueng-Arporn, Naporn;Matrakool, Likit;Tongtawee, Taweesak;Rujirakul, Ratana;Nimkhuntod, Porntip;Wakhuwathapong, Parichart;Kaewpitoon, Natthawut 8391
Thailand is becoming an aging society, this presenting as a serious problem situation especially regarding health. Chronic diseases found frequently in the elderly may be related to dietary intake and life style. Surin province has been reported as a risk area for liver fluke with a high incidence of cholangiocarcinma especially in the elderly. Therefore, this study aimed to determine the nutritional status and associated factors among elderly in Surin province, northeast of Thailand. A community-based cross-sectional study was conducted among 405 people aged 60 years and above, between September 2012 and July 2014. The participants were selected through a randomized systematic sampling method and completed a pre-designed questionnaire with general information, food recorded, weight, height, waist circumference, and behavior regarding to food consume related to liver fluke infection. The data were analyzed using descriptive statistics and Spearman's rank correlation coefficients. The majority of participants was female (63.5%), age between 60-70 years old (75.6%), with elementary school education (96.6%), living with their (78.9%), and having underlying diseases (38.3%). Carbohydrate (95.3%) was need to improve the consumption. The participants demonstrated under-nutrition (24.4%), over-nutrition (16.4%), and obesity (15.4%). Elderly had a waist circumference as the higher than normal level (34.0%). Gender, female, age 71-80 years old, elementary school and underlying diseases were significantly associated with poor nutritional status. The majority of them had a high knowledge (43.0%), moderate attitude (44.4%), and moderate practice (46.2%) regarding food consumption related to liver fluke infection. In conclusion, these findings data indicated that elderly age group often have an under- or over-nutritional status. Carbohydrate consumption needs to be improved. Some elderly show behavior regarding food consumption that is related to liver fluke infection hat needs to be improved, so that health education pertaining good nutrition is required. -
Bandala, Cindy;De la Garza-Montano, Paloma;Cortes-Algara, Alfredo;Cruz-Lopez, Jaime;Dominguez-Rubio, Rene;Gonzalez-Lopez, Nelly Judith;Cardenas-Rodriguez, Noemi;Alfaro-Rodriguez, A;Salcedo, M;Floriano-Sanchez, E;Lara-Padilla, Eleazar 8397
Background: Breast cancer (BCa) is the most common malignancy in Mexican women. A set of histopathological markers has been established to guide BCa diagnosis, prognosis and treatment. Nevertheless, in only a few Mexican health services, such as that of the Secretariat of National Defense (SEDENA for its acronym in Spanish), are these markers commonly employed for assessing BCa. The aim of this study was to explore the association of Ki67, TP53, HER2/neu, estrogenic receptors (ERs) and progesterone receptors (PRs) with BCa risk factors. Materials and Methods: Clinical histories provided background patient information. Immunohistochemical (IHC) analysis was conducted on 48 tissue samples from women diagnosed with BCa and treated with radical mastectomy. The Chi square test or Fisher exact test together with the Pearson and Spearman correlation were applied. Results: On average, patients were$58{\pm}10.4$ years old. It was most common to find invasive ductal carcinoma (95.8%), histological grade 3 (45.8%), with a poor Nottingham Prognostic Index (NPI; 80.4%). ERs and PRs were associated with smoking and alcohol consumption, metastasis at diagnosis and Ki67 expression (p<0.05). PR+ was also related to urea and ER+ (p<0.05). Ki67 was associated with TP53 and elevated triglycerides (p<0.05), and HER2/neu with ER+, the number of pregnancies and tumor size (p<0.05). TP53 was also associated with a poor NPI (p<0.05) and CD34 with smoking (p<0.05). The triple negative status (ER-/PR-/HER2/neu-) was related to smoking, alcohol consumption, exposure to biomass, number of pregnancies, metastasis and a poor NPI (p<0.05). Moreover, the luminal B subty was associated with histological type (p=0.007), tumor size (p=0.03) and high cholesterol (p=0.02). Conclusions: Ki67, TP53, HER2/neu, ER and PR proved to be related to several clinical and pathological factors. Hence, it is crucial to determine this IHC profile in women at risk for BCa. Certain associations require further study to understand physiological/biochemical/molecular processes. -
Chanthra, Nawin;Payungporn, Sunchai;Chuaypen, Natthaya;Piratanantatavorn, Kesmanee;Pinjaroen, Nutcha;Poovorawan, Yong;Tangkijvanich, Pisit 8405
Hepatitis B virus (HBV) infection is the leading cause of hepatocellular carcinoma (HCC) development. Recent studies demonstrated that single nucleotide polymorphisms (SNPs) rs2293152 in signal transducer and activator of transcription 3 (STAT3) and rs7574865 in signal transducer and activator of transcription 4 (STAT4) are associated with chronic hepatitis B (CHB)-related HCC in the Chinese population. We hypothesized that these polymorphisms might be related to HCC susceptibility in Thai population as well. Study subjects were divided into 3 groups consisting of CHB-related HCC (n=192), CHB without HCC (n=200) and healthy controls (n=190). The studied SNPs were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results showed that the distribution of different genotypes for both polymorphisms were in Hardy-Weinberg equilibrium (P>0.05). Our data demonstrated positive association of rs7574865 with HCC risk when compared to healthy controls under an additive model (GG versus TT: odds ratio (OR)=2.07, 95% confidence interval (CI)=1.06-4.03, P=0.033). This correlation remained significant under allelic and recessive models (OR=1.46, 95% CI=1.09-1.96, P=0.012 and OR=1.71, 95% CI=1.13-2.59, P=0.011, respectively). However, no significant association between rs2293152 and HCC development was observed. These data suggest that SNP rs7574865 in STAT4 might contribute to progression to HCC in the Thai population. -
Abdel-Rahman, Salah;Shaban, Nadia;Haggag, Amany;Awad, Doaa;Bassiouny, Ahmad;Talaat, Iman 8411
The effect of Eruca sativa seed extract (SE) on nuclear factor kappa B (NF-${\kappa}B$ ), cyclooxygenase-2 (COX-2) and B-cell lymphoma-2 (Bcl-2) gene expression levels was investigated in rat mammary gland carcinogenesis induced by 7,12 dimethylbenz(${\alpha}$ )anthracene (DMBA). DMBA increased NF-${\kappa}B$ , COX-2 and Bcl-2 gene expression levels and lipid peroxidation (LP), while, decreased glutathione-S-transferase (GST) and superoxide dismutase (SOD) activities and total antioxidant concentration (TAC) compared to the control group. After DMBA administration, SE treatment reduced NF-${\kappa}B$ , COX-2 and Bcl-2 gene expression levels and LP. Hence, SE treatment reduced inflammation and cell proliferation, while increasing apoptosis, GST and SOD activities and TAC. Analysis revealed that SE has high concentrations of total flavonoids, triterpenoids, alkaloids and polyphenolic compounds such as gallic, chlorogenic, caffeic, 3,4-dicaffeoyl quinic, 3,5-dicaffeoyl quinic, tannic, cinnamic acids, catechin and phloridzin. These findings indicate that SE may be considered a promising natural product from cruciferous vegetables against breast cancer, especially given its high antioxidant properties. -
Verma, Shiv Prakash;Sisoudiya, Saumya;Das, Parimal 8419
Purpose: Anti-cancer activity evaluation of aqueous extract of CRUEL (herbomineral formulation) capsules on renal cell carcinoma cell lines, and exploration of mechanisms of cell death. Materials and Methods: To detect the cytotoxic dose concentration in renal cell carcinoma (RCC) cells, MTT assays were performed and morphological changes after treatment were observed by inverted microscopy. Drug effects against RCC cell lines were assessed with reference to cell cycle distribution (flow cytometry), anti-metastatic potential (wound healing assay) and autophagy(RT-PCR). Results: CRUEL showed anti-proliferative effects against RCC tumor cell lines with an IC50 value of${\approx}4mg/mL$ in vitro., while inducing cell cycle arrest at S-phase of cell cycle and inhibiting wound healing. LC3 was found to be up-regulated after drug treatment in RT-PCR resulting in an autophagy mode of cell death. Conclusions: This study provides the experimental validation for antitumor activity of CRUEL. -
Fayek, Ihab Samy;Kamel, Ahmed Ahmed;Sidhom, Nevine FH 8425
Purpose: To study the safety of prophylactic level VII nodal dissection regarding hypoparathyroidism (temporary and permanent) and vocal cord dysfunction (temporary and permanent) and its impact on disease free survival. Materials and Methods: This prospective study concerned 63 patients with papillary thyroid carcinoma with N0 neck node involvement (clinically and radiologically) in the period from December 2009 to May 2013. All patients underwent total thyroidectomy and prophylactic central neck dissection including levels VI and VII lymph nodes in group A (31 patients) and level VI only in group B (32 patients). The thyroid gland, level VI and level VII lymph nodes were each examined histopathologically separately for tumor size, multicentricity, bilaterality, extrathyroidal extension, number of dissected LNs and metastatic LNs. Follow-up of both groups, regarding hypoparathyroidism, vocal cord dysfunction and DFS, ranged from 6-61 months. Results: The mean age was 34.8 and 34.3, female predominance in both groups with F: M 24:7 and 27:5 in groups A and B, respectively. Mean tumor size was 12.6 and 14.7mm. No statistical differences were found between both groups regarding age, sex, bilaterality, multicentricity or extrathyroidal extension. The mean no. of dissected level VI LNs was 5.06 and 4.72 and mean no. of metastatic level VI was 1 and 0.84 in groups A and B, respectively. The mean no. of dissected level VII LNs was 2.16 and mean no. of metastatic LNs was 0.48. Postoperatively temporary hypoparathyroidism was detected in 10 and 7 patients and permanent hypoparathyroidism in 2 and 3 patients; temporary vocal cord dysfunction was detected in 4 patients and one patient, and permanent vocal cord dysfunction in one and 2 patients in groups A and B, respectively. No significant statistical differences were noted between the 2 groups regarding hypoparathyroidism (P=0.535) or vocal cord dysfunction (P=0.956). The number of dissected LNs at level VI only significantly affected the occurrence of hypoparathyroidism (<0.001) and vocal cord dysfunction (<0.001).The DFS was significantly affected by bilaterality, multicentricity and extrathyroidal extension. Conclusions: Level VII nodal dissection is a safe procedure complementary to level VI nodal dissection with prophylactic central neck dissection for papillary thyroid carcinoma. -
Islamian, Jalil Pirayesh;Aghaee, Fahimeh;Farajollahi, Alireza;Baradaran, Behzad;Fazel, Mona 8431
Doxorubicin (DOX) was introduced as an effective chemotherapeutic for a wide range of cancers but with some severe side effects especially on myocardia. 2-Deoxy-D-glucose (2DG) enhances the damage caused by chemotherapeutics and ionizing radiation (IR) selectively in cancer cells. We have studied the effects of$1{\mu}M$ DOX and$500{\mu}M$ 2DG on radiation induced cell death, apoptosis and also on the expression levels of p53 and PTEN genes in T47D and SKBR3 breast cancer cells irradiated with 100, 150 and 200 cGy x-rays. DOX and 2DG treatments resulted in altered radiation-induced expression levels of p53 and PTEN genes in T47D as well as SKBR3 cells. In addition, the combination along with IR decreased the viability of both cell lines. The radiobiological parameter (D0) of T47D cells treated with 2DG/DOX and IR was 140 cGy compared to 160 cGy obtained with IR alone. The same parameters for SKBR3 cell lines were calculated as 120 and 140 cGy, respectively. The sensitivity enhancement ratios (SERs) for the combined chemo-radiotherapy on T47D and SKBR3 cell lines were 1.14 and 1.16, respectively. According to the obtained results, the combination treatment may use as an effective targeted treatment of breast cancer either by reducing the single modality treatment side effects. -
Ghoncheh, Mahshid;Mirzaei, Maryam;Salehiniya, Hamid 8439
Background: Breast cancer is the most common malignancy in women worldwide and its incidence is generally increasing. In 2012, it was the second most common cancer in the world. It is necessary to obtain information on incidence and mortality for health planning. This study aimed to investigate the relationship between the human development index (HDI), and the incidence and mortality rates of breast cancer in the world in 2012. Materials and Methods: This ecologic study concerns incidence rate and standardized mortality rates of the cancer from GLOBOCAN in 2012, and HDI and its components extracted from the global bank site. Data were analyzed using correlation tests and regression with SPSS software (version 15). Results: Among the six regions of WHO, the highest breast cancer incidence rate (67.6) was observed in the PAHO, and the lowest incidence rate was 27.8 for SEARO. There was a direct, strong, and meaningful correlation between the standardized incidence rate and HDI (r=0.725,$p{\leq}0.001$ ). Pearson correlation test showed that there was a significant correlation between age-specific incidence rate (ASIR) and components of the HDI (life expectancy at birth, mean years of schooling, and GNP). On the other, a non-significant relationship was observed between ASIR and HDI overall (r=0.091, p=0.241). In total, a significant relationship was not found between age-specific mortality rate (ASMR) and components of HDI. Conclusions: Significant positive correlations exist between ASIR and components of the HDI. Socioeconomic status is directly related to the stage of the cancer and patient's survival. With increasing the incidence rate of the cancer, mortality rate from the cancer does not necessariloy increase. This may be due to more early detection and treatment in developed that developing countries. It is necessary to increase awareness of risk factors and early detection in the latter. -
Amirfakhri, Siamak;Salimi, Arsalan;Fernandez, Nelson 8445
Background: Breast cancer is the most common neoplasm in women and the most frequent cause of death in those between 35 and 55 years of age. All multicellular organisms have an innate immune system, whereas the adaptive or 'acquired' immune system is restricted to vertebrates. This study focused on the effect of conditioned medium isolated from cultured breast cancer cells on NB4 neutrophil-like cells. Materials and Methods: In the current study neutrophil-like NB4 cells were incubated with MCF-7 cell-conditioned medium. After 6 h incubation the intracellular receptor TLR2, was analyzed. Results: The results revealed that MCF-7 cell-conditioned medium elicited expression of TLR2 in NB4 cells. Conclusions: This treatment would result in the production of particular stimulants (i.e. soluble cytokines), eliciting the expression of immune system receptors. Furthermore, the flow cytometry results demonstrated that MCF-7 cell-conditioned medium elicited an effect on TLR2 intracellular receptors. -
Background: Gallbladder cancer (GBC) is a rare but highly invasive malignancy characterized by poor survival. In a national cancer survey, the age-standardized incidence rate of GBC was highest in Jeju Island among the 15 provinces in South Korea. The aim of this descriptive epidemiological study was to suggest the modifiable risk factors for this rare malignant disease in Jeju Island by performing an age-sex-matched case-control study. Materials and Methods: The case group included patients diagnosed with GBC at the Department of Internal Medicine of Cheju Halla General Hospital, Jeju, South Korea, within the 5-year study period. The control group consisted of age-sex-matched subjects selected from among the participants of the health promotion center at the same institute and in the same period. We compared 78 case-control pairs in terms of clinical variables such as histories of hypertension, diabetes, vascular occlusive disorders, alcohol and smoking consumption, obesity, and combined polypoid lesions of the gallbladder (PLG) or gallstone diseases (GSDs). Results: Among the relevant risk factors, alcohol consumption, parity
${\geq}2$ , PLG, and GSDs were significant risk factors in the univariate analysis. PLG (p < 0.01; OR, 51.1; 95% confidence interval [CI], 2.98-875.3) and GSD (p < 0.01; OR, 54.9; 95% CI, 3.00-1001.8) were associated risk factors of GBC in the multivariate analysis with the conditional logistic regression model. However, we failed to find any correlation between obesity and GBC. We also found a negative correlation between alcohol consumption history and GBC in the multivariate analysis (p < 0.01; OR, 0.06; 95% CI, 0.01-0.31). Conclusions: These results suggest that combined PLG and GSDs are strongly associated with the GBC in Jeju Island and mild to moderate alcohol consumption may negatively correlate with GBC risk. -
Symonds, Erin L;Pedersen, Susanne;Cole, Stephen R;Massolino, Joseph;Byrne, Daniel;Guy, John;Backhouse, Patricia;Fraser, Robert J;LaPointe, Lawrence;Young, Graeme P 8455
Background: Poor participation rates are often observed in colorectal cancer (CRC) screening programs utilising faecal occult blood tests. This may be from dislike of faecal sampling, or having benign bleeding conditions that can interfere with test results. These barriers may be circumvented by offering a blood-based DNA test for screening. The aim was to determine if program participation could be increased by offering a blood test following faecal immunochemical test (FIT) non-participation. Materials and Methods: People were invited into a CRC screening study through their General Practice and randomised into control or intervention (n=600/group). Both groups were mailed a FIT (matching conventional screening programs). Participation was defined as FIT completion within 12wk. Intervention group non-participants were offered a screening blood test (methylated BCAT1/IKZF1). Overall participation was compared between the groups. Results: After 12wk, FIT participation was 82% and 81% in the control and intervention groups. In the intervention 96 FIT nonparticipants were offered the blood test - 22 completed this test and 19 completed the FIT instead. Total screening in the intervention group was greater than the control (88% vs 82%, p<0.01). Of 12 invitees who indicated that FIT was inappropriate for them (mainly due to bleeding conditions), 10 completed the blood test (83%). Conclusions: Offering a blood test to FIT non-participants increased overall screening participation compared to a conventional FIT program. Blood test participation was particularly high in invitees who considered FIT to be inappropriate for them. A blood test may be a useful adjunct test within a FIT program. -
Shabestarian, Hoda;Ghodsi, Mohammad;Mallak, Afsaneh Javdani;Jafarian, Amir Hossein;Montazer, Mehdi;Forghanifard, Mohammad Mahdi 8461
Gastric cancer (GC) as the fourth most common cause of malignancies shows high rate of morbidity appropriating the second leading cause of cancer-related death worldwide. Developmental pluripotency associated-2 (DPPA2), cancer-testis antigen (CT100), is commonly expressed only in the human germ line and pluripotent embryonic cells but it is also present in a significant subset of malignant tumors. To investigate whether or not DPPA2 expression is recalled in GC, our aim in this study was to elucidate DPPA2 protein expression in gastric cancer. Fifty five GC tumor and their related margin normal tissues were recruited to evaluate DPPA2 protein expression and its probable associations with different clinicopathological features of the patients. DPPA2 was overexpressed in GC cases compared with normal tissues (P < .005). While DPPA2 expression was detected in all GC samples, its high expression was found in 23 of 55 tumor tissues (41.8%). Interestingly, 50 of 55 normal samples (90.9%) were negative for DPPA2 protein expression and remained 5 samples showed very low expression of DPPA2. DPPA2 protein expression in GC was significantly correlated with lymph node metastasis (p = 0.012). The clinical relevance of DPPA2 in GC illustrated that high level expression of this protein was associated with lymph node metastasis supporting this hypothesis that alteration in DPPA2 was associated with aggressiveness of gastric cancer and may be an early event in progression of the disease. DPPA2 may be introduced as a new marker for invasive and metastatic GCs. -
Mansoori, Maryam;Golalipour, Masoud;Alizadeh, Shahriar;Jahangirerad, Ataollah;Khandozi, Seyed Reza;Fakharai, Habibollah;Shahbazi, Majid 8467
Background: One of the major mechanisms for drug resistance is associated with altered anticancer drug transport, mediated by the human-adenosine triphosphate binding cassette (ABC) transporter superfamily proteins. The overexpression of adenosine triphosphate binding cassette, sub-family B, member 1 (ABCB1) by multidrug-resistant cancer cells is a serious impediment to chemotherapy. In our study we have studied the possibility that structural single-nucleotide polymorphisms (SNP) are the mechanism of ABCB1 overexpression. Materials and Methods: A total of 101 gastric cancer multidrug resistant cases and 100 controls were genotyped with sequence-specific primed PCR (SSP-PCR). Gene expression was evaluated for 70 multidrug resistant cases and 54 controls by real time PCR. The correlation between the two groups was based on secondary structures of RNA predicted by bioinformatics tool. Results: The results of genotyping showed that among 3 studied SNPs, rs28381943 and rs2032586 had significant differences between patient and control groups but there were no differences in the two groups for C3435T. The results of real time PCR showed over-expression of ABCB1 when we compared our data with each of the genotypes in average mode. Prediction of secondary structures in the existence of 2 related SNPs (rs28381943 and rs2032586) showed that the amount of${\Delta}G$ for original mRNA is higher than the amount of${\Delta}G$ for the two mentioned SNPs. Conclusions: We have observed that 2 of our studied SNPs (rs283821943 and rs2032586) may elevate the expression of ABCB1 gene, through increase in mRNA stability, while this was not the case for C3435T. -
Swarnapriya, K;Kavitha, D;Reddy, Gopireddy Murali Mohan 8473
Background: High risk human papilloma virus (HPV) types 16 and 18 have been proven as central causes of cervical cancer and safety and immunogenicity of HPV vaccines are sufficiently established. Knowledge and practices of HPV vaccination among medical and paramedical students is vital as these may strongly determine intention to recommend vaccination to others in the future. The present study was therefore undertaken to assess the knowledge, attitude and practices regarding cervical cancer screening and HPV vaccination among medical and paramedical students and to analyze factors influencing them. Materials and Methods: The present cross sectional study, conducted in a tertiary care teaching hospital in south India, included undergraduate students aged 18 years and above, belonging to medical, dental and nursing streams, after informed written consent. Results: Out of 957 participants, only 430 (44.9%) displayed good knowledge and only 65 (6.8%) had received HPV vaccination. Among the unvaccinated, 433 (48.54%), were not willing to take the vaccine. Concerns regarding the efficacy (30.5%), safety (26.1%) and cost of the vaccine (21.7%) were responsible for this. Age, gender, family history of malignancy and mother's education had no influence on knowledge. Compared to medical students, nursing students had better knowledge (OR-1.49, 95% CI 0.96 to 2.3, p = 0.072) and students of dentistry had poor knowledge (OR-0.50 95% CI 0.36 to 0.70, p<0.001). Conclusions: The knowledge and uptake of HPV vaccination among medical and paramedical students in India is poor. Targeted health education interventions may have huge positive impact not only on the acceptance of vaccination among them, but also on their intention to recommend the vaccine in future. -
Taha, Hana;Jaghbeer, Madi Al;Shteiwi, Musa;AlKhaldi, Sireen;Berggren, Vanja 8479
Background: Colorectal cancer (CRC) is the third most common cancer globally. In Jordan, it is the number one cancer among men and the second most common cancer among women, accounting for 15% and 9.4% respectively of all male and female diagnosed cancers. This study aimed to evaluate the knowledge and perceptions about colorectal cancer risk factors, signs and symptoms in Jordan and to provide useful data about the best modes of disseminating preventive messages about the disease. Materials and Methods: A stratified clustered random sampling technique was used to recruit 300 males and 300 females aged 30 to 65 years without a previous history of CRC from four governorates in Jordan. A semi-structured questionnaire and face to face interviews were employed. Descriptive and multivariate analysis was applied to assess knowledge and perceptions about CRC. Results: Both males and females perceived their CRC risk to be low. They had low knowledge scores about CRC with no significant gender association (P=0.47). From a maximum knowledge score of 18 points, the median scores of males and females were 4 points (SD=2.346, range 0-13) and 4 points (SD=2.329, range 0-11) respectively. Better knowledge scores were associated with governorate, higher educational level, older age, higher income, having a chronic disease, having a family history of CRC, previously knowing someone who had CRC and their doctor's knowledge about their family history of CRC. Conclusions: There is a low level of knowledge about CRC and underestimation of risk among the study participants. This underlines the need for public health interventions to create awareness about the illness. It also calls for further research to assess the knowledge and perceptions about CRC early detection examinations in Jordan. -
Tongtawee, Taweesak;Dechsukhum, Chavaboon;Leeanansaksiri, Wilairat;Kaewpitoon, Soraya;Kaewpitoon, Natthawut;Loyd, Ryan A;Matrakool, Likit;Panpimanmas, Sukij 8487
Background: Helicobacter pylori infection and premalignant gastric mucosa can be reliably identified using conventional narrow band imaging (C-NBI) gastroscopy. The aim of our study was to compare standard biopsy with site specific biopsy for diagnosis of H. pylori infection and premalignant gastric mucosa in daily clinical practice. Materials and Methods: Of a total of 500 patients who underwent gastroscopy for investigation of dyspeptic symptoms, 250 patients underwent site specific biopsy using C-NBI (Group 1) and 250 standard biopsy (Group 2). Sensitivity, specificity, and positive and negative predictive values were assessed. The efficacy of detecting H. pylori associated gastritis and premalignant gastric mucosa according to the updated Sydney classification was also compared. Results: In group 1 the sensitivity, specificity, positive and negative predictive values for predicting H. pylori positivity were 95.4%, 97.3%, 98.8% and 90.0% respectively, compared to 92.9%, 88.6%, 83.2% and 76.1% in group 2. Site specific biopsy was more effective than standard biopsy in terms of both H. pylori infection status and premalignant gastric mucosa detection (P<0.01). Conclusions: Site specific biopsy using C-NBI can improve detection of H. pylori infection and premalignant gastric mucosa in daily clinical practice. -
Kituncharoen, Saroot;Tantbirojn, Patou;Niruthisard, Somchai 8491
Purpose: To compare unsatisfactory rates and detection of abnormal cervical cytology between conventional cytology or Papanicolaou smear (CC) and liquid-based cytology (LBC). Materials and Methods: A total of 23,030 cases of cervical cytology performed at King Chulalongkorn Memorial Hospital during 2012-2013 were reviewed. The percentage unsatisfactory and detection rates of abnormal cytology were compared between CC and LBC methods. Results: There was no difference in unsatisfactory rates between CC and LBC methods (0.1% vs. 0.1%, p = 0.84). The detection rate for squamous cell abnormalities was significantly higher with the LBC method (7.7% vs. 11.5%, p < 0.001), but those for overall abnormal glandular epithelium were similar (0.4% vs. 0.6%, p = 0.13). Low grade squamous lesion (ASC-US and LSIL) were more frequently detected by the LBC method (6.1% vs. 9.5%, p < 0.001). However, there was no difference in high gradd squamous lesions (1.1% vs. 1.1%, p = 0.95). When comparing between types of glandular abnormality, there was no significant difference the groups. Conclusions: There was no difference in unsatisfactory rates between the conventional smear and LBC. However, LBC could detect low grade squamous cell abnormalities more than CC, while there were similar rates of detection of high grade squamous cell lesions and glandular cell abnormalities. -
Latiff, Latiffah A;Ibrahim, Zaidah;Pei, Chong Pei;Rahman, Sabariah Abdul;Akhtari-Zavare, Mehrnoosh 8495
Purpose: This study was conducted to assess the agreement and differences between cervical self-sampling with a Kato device (KSSD) and gynecologist sampling for Pap cytology and human papillomavirus DNA (HPV DNA) detection. Materials and Methods: Women underwent self-sampling followed by gynecologist sampling during screening at two primary health clinics. Pap cytology of cervical specimens was evaluated for specimen adequacy, presence of endocervical cells or transformation zone cells and cytological interpretation for cells abnormalities. Cervical specimens were also extracted and tested for HPV DNA detection. Positive HPV smears underwent gene sequencing and HPV genotyping by referring to the online NCBI gene bank. Results were compared between samplings by Kappa agreement and McNemar test. Results: For Pap specimen adequacy, KSSD showed 100% agreement with gynecologist sampling but had only 32.3% agreement for presence of endocervical cells. Both sampling showed 100% agreement with only 1 case detected HSIL favouring CIN2 for cytology result. HPV DNA detection showed 86.2%agreement (K=0.64, 95% CI 0.524-0.756, p=0.001) between samplings. KSSD and gynaecologist sampling identified high risk HPV in 17.3% and 23.9% respectively (p=0.014). Conclusion: The self-sampling using Kato device can serve as a tool in Pap cytology and HPV DNA detection in low resource settings in Malaysia. Self-sampling devices such as KSSD can be used as an alternative technique to gynaecologist sampling for cervical cancer screening among rural populations in Malaysia. -
Gajek, Arkadiusz;Denel-Bobrowska, Marta;Rogalska, Aneta;Bukowska, Barbara;Maszewski, Janusz;Marczak, Agnieszka 8503
The purpose of this study was to provide a detailed explanation of the mechanism of bisanthracycline, WP 631 in comparison to doxorubicin (DOX), a first generation anthracycline, currently the most widely used pharmaceutical in clinical oncology. Experiments were performed in SKOV-3 ovarian cancer cells which are otherwise resistant to standard drugs such as cis-platinum and adriamycin. As attention was focused on the ability of WP 631 to induce apoptosis, this was examined using a double staining method with Annexin V and propidium iodide probes, with measurement of the level of intracellular calcium ions and cytosolic cytochrome c. The western blotting technique was performed to confirm PARP cleavage. We also investigated the involvement of caspase activation and DNA degradation (comet assay and immunocytochemical detection of phosphorylated H2AX histones) in the development of apoptotic events. WP 631 demonstrated significantly higher effectiveness as a pro-apoptotic drug than DOX. This was evident in the higher levels of markers of apoptosis, such as the externalization of phosphatidylserine and the elevated level of cytochrome c. An extension of incubation time led to an increase in intracellular calcium levels after treatment with DOX. Lower changes in the calcium content were associated with the influence of WP 631. DOX led to the activation of all tested caspases, 8, 9 and 3, whereas WP 631 only induced an increase in caspase 8 activity after 24h of treatment and consequently led to the cleavage of PARP. The lack of active caspase 3 had no outcome on the single and double-stranded DNA breaks. The obtained results show that WP 631 was considerably more genotoxic towards the investigated cell line than DOX. This effect was especially visible after longer times of incubation. The above detailed studies indicate that WP 631 generates early apoptosis and cell death independent of caspase-3, detected at relatively late time points. The observed differences in the mechanisms of the action of WP631 and DOX suggest that this bisanthracycline can be an effective alternative in ovarian cancer treatment. -
Abdullah, Matin Mellor;Mohamed, Ahmad Kamal;Foo, Yoke Ching;Lee, Catherine May Ling;Chua, Chin Teong;Wu, Chin Huei;Hoo, LP;Lim, Teck Onn;Yen, Sze Whey 8513
Background: GLOBOCAN12 recently reported high cancer mortality in Malaysia suggesting its cancer health services are under-performing. Cancer survival is a key index of the overall effectiveness of health services in the management of patients. This report focuses on Subang Jaya Medical Centre (SJMC) care performance as measured by patient survival outcome for up to 5 years. Materials and Methods: All women with breast cancer treated at SJMC between 2008 and 2012 were enrolled for this observational cohort study. Mortality outcome was ascertained through record linkage with national death register, linkage with hospital registration system and finally through direct contact by phone or home visits. Results: A total of 675 patients treated between 2008 and 2012 were included in the present survival analysis, 65% with early breast cancer, 20% with locally advanced breast cancer (LABC) and 4% with metastatic breast cancer (MBC). The overall relative survival (RS) at 5 years was 88%. RS for stage I was 100% and for stage II, III and IV disease was 95%, 69% and 36% respectively. Conclusions: SJMC is among the first hospitals in Malaysia to embark on routine measurement of the performance of its cancer care services and its results are comparable to any leading centers in developed countries. -
Rahnama, Mozhgan;Khoshknab, Masoud Fallahi;Maddah, Sadat Seyed Bagher;Ahmadi, Fazlollah;Arbabisarjou, Azizollah 8519
After diagnosis of cancer, many patients show more inclination towards religion and religious activities. This qualitative study using semi-structured interviews explored the perspectives and experiences of 17 Iranian cancer patients and their families regarding the role of religion in their adaptation to cancer in one of the hospitals in Tehran and a charity institute. The content analysis identified two themes: "religious beliefs" (illness as God's will, being cured by God's will, belief in God's supportiveness, having faith in God as a relieving factor, and hope in divine healing) and "relationship with God during the illness." In general, relationship with God and religious beliefs had a positive effect on the patients adapting to their condition, without negative consequences such as stopping their treatment process and just waiting to be cured by God. Thus a strengthening of such beliefs, as a coping factor, could be recommended through religious counseling. -
Khoshnaw, Najmaddin;Mohammed, Hazha A;Abdullah, Dana A 8525
Background: Cancer has become a major health problem associated with high mortality worldwide, especially in developing countries. The aim of our study was to evaluate the incidence rates of different types of cancer in Sulaymaniyah from January-2006 to January-2014. The data were compared with those reported for other middle east countries. Materials and Methods: This retrospective study depended on data collected from Hiwa hospital cancer registry unit, death records and histopathology reports in all Sulaymaniyah teaching hospitals, using international classification of diseases. Results: A total of 8,031 cases were registered during the eight year period, the annual incidence rate in all age groups rose from 38 to 61.7 cases/100,000 population/year, with averages over 50 in males and 50.7 in females. The male to female ratio in all age groups were 0.98, while in the pediatric age group it was 1.33. The hematological malignancies in all age groups accounted for 20% but in the pediatric group around half of all cancer cases. Pediatric cancers were occluding 7% of total cancers with rates of 10.3 in boys and 8.7 in girls. The commonest malignancies by primary site were leukemia, lymphoma, brain, kidney and bone. In males in all age groups they were lung, leukaemia, lymphoma, colorectal, prostate, bladder, brain, stomach, carcinoma of unknown primary (CUP) and skin, while in females they were breast, leukaemia, lymphoma, colorectal, ovary, lung, brain, CUP, and stomach. Most cancers were increased with increasing age except breast cancer where decrease was noted in older ages. High mortality rates were found with leukemia, lung, lymphoma, colorectal, breast and stomach cancers. Conclusions: We here found an increase in annual cancer incidence rates across the period of study, because of increase of cancer with age and higher rates of hematological malignancies. Our study is valuable for Kurdistan and Iraq because it provides more accurate data about the exact patterns of cancer and mortality in our region. -
Valizadeh, Armita;Ahmadzadeh, Ahmad;Saki, Ghasem;Khodadadi, Ali;Teimoori, Ali 8533
Background: B-cell chronic lymphocytic leukemia B (B-CLL), the most common type of leukemia, may be caused by apoptosis deficiency in the body. Adipose tissue-derived mesenchymal stem cells (AD-MSCs) as providers of pro-apoptotic molecules such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), can be considered as an effective anti-cancer therapy candidate. Therefore, in this study we assessed the role of tumor necrosis factor-producing mesenchymal stem cells oin apoptosis of B-CLL cells resistant to fludarabine-based chemotherapy. Materials and Methods: In this study, after isolation and culture of AD-MSCs, a lentiviral LeGO-iG2-TRAIL-GFP vector containing a gene producing the ligand pro-apoptotic with plasmid PsPAX2 and PMDG2 virus were transfected into cell-lines to generate T293HEK. Then, T293HEK cell supernatant containing the virus produced after 48 and 72 hours was collected, and these viruses were transduced to reprogram AD-MSCs. Apoptosis rates were separately studied in four groups: group 1, AD-MSCs-TRAIL; group 2, AD-MSCs-GFP; group 3, AD-MSCs; and group 4, CLL. Results: Observed apoptosis rates were: group 1,$42{\pm}1.04%$ ; group 2,$21{\pm}0.57%$ ; group 3,$19{\pm}2.6%$ ; and group 4, %$0.01{\pm}0.01$ . The highest rate of apoptosis thus occurred ingroup 1 (transduced TRAIL encoding vector). In this group, the average medium-soluble TRAIL was 72.7pg/m and flow cytometry analysis showed a pro-apoptosis rate of$63{\pm}1.6%$ , which was again higher than in other groups. Conclusions: In this study we have shown that tumor necrosis factor (TNF) secreted by AD-MSCs may play an effective role in inducing B-CLL cell apoptosis. -
Mukem, Suwanna;Meng, Qingyue;Sriplung, Hutcha;Tangcharoensathien, Viroj 8541
Background: The coverage of breast and cervical cancer screening has only slightly increased in the past decade in Thailand, and these cancers remain leading causes of death among women. This study identified socioeconomic and contextual factors contributing to the variation in screening uptake and coverage. Materials and Methods: Secondary data from two nationally representative household surveys, the Health and Welfare Survey (HWS) 2007 and the Reproductive Health Survey (RHS) 2009 conducted by the National Statistical Office were used. The study samples comprised 26,951 women aged 30-59 in the 2009 RHS, and 14,619 women aged 35 years and older in the 2007 HWS were analyzed. Households of women were grouped into wealth quintiles, by asset index derived from Principal components analysis. Descriptive and logistic regression analyses were performed. Results: Screening rates for cervical and breast cancers increased between 2007 and 2009. Education and health insurance coverage including wealth were factors contributing to screening uptake. Lower or non-educated and poor women had lower uptake of screenings, as were young, unmarried, and non-Buddhist women. Coverage of the Civil Servant Medical Benefit Scheme increased the propensity of having both screenings, while the universal coverage scheme increased the probability of cervical screening among the poor. Lack of awareness and knowledge contributed to non-use of both screenings. Women were put off from screening, especially Muslim women on cervical screening, because of embarrassment, fear of pain and other reasons. Conclusions: Although cervical screening is covered by the benefit package of three main public health insurance schemes, free of charge to all eligible women, the low coverage of cervical screening should be addressed by increasing awareness and strengthening the supply side. As mammography was not cost effective and not covered by any scheme, awareness and practice of breast self examination and effective clinical breast examination are recommended. Removal of cultural barriers is essential. -
Saberi, Alihossein;Khodamoradi, Ehsan;Birgani, Mohammad Javad Tahmasebi;Makvandi, Manoochehr 8553
Background: Accurate dose assessment and correct identification of irradiated from non-irradiated people are goals of biological dosimetry in radiation accidents. Objectives: Changes in the FDXR and the RAD51 gene expression (GE) levels were here analyzed in response to total body exposure (TBE) to a 6 MV x-ray beam in rats. We determined the accuracy for absolute quantification of GE to predict the dose at 24 hours. Materials and Methods: For this in vivo experimental study, using simple randomized sampling, peripheral blood samples were collected from a total of 20 Wistar rats at 24 hours following exposure of total body to 6 MV X-ray beam energy with doses (0.2, 0.5, 2 and 4 Gy) for TBE in Linac Varian 2100C/D (Varian, USA) in Golestan Hospital, in Ahvaz, Iran. Also, 9 rats was irradiated with a 6MV X-ray beam at doses of 1, 2, 3 Gy in 6MV energy as a validation group. A sham group was also included. After RNA extraction and DNA synthesis, GE changes were measured by the QRT-PCR technique and an absolute quantification strategy by taqman methodology in peripheral blood from rats. ROC analysis was used to distinguish irradiated from non-irradiated samples (qualitative dose assessment) at a dose of 2 Gy. Results: The best fits for mean of responses were polynomial equations with a R2 of 0.98 and 0.90 (for FDXR and RAD51 dose response curves, respectively). Dose response of the FDXR gene produced a better mean dose estimation of irradiated "validation" samples compared to the RAD51 gene at doses of 1, 2 and 3 Gy. FDXR gene expression separated the irradiated rats from controls with a sensitivity, specificity and accuracy of 87.5%, 83.5% and 81.3%, respectively, 24 hours after dose of 2 Gy. These values were significantly (p<0.05) higher than the 75%, 75% and 75%, respectively, obtained using gene expression of RAD51 analysis at a dose of 2 Gy. Conclusions: Collectively, these data suggest that absolute quantification by gel purified quantitative RT-PCR can be used to measure the mRNA copies for GE biodosimetry studies at comparable accuracy to similar methods. In the case of TBE with 6MV energy, FDXR gene expression analysis is more precise than that with RAD51 for quantitative and qualitative dose assessment. -
Xu, Chuan;Huang, Xin-En;Lv, Peng-Hua;Wang, Shu-Xiang;Sun, Ling;Wang, Fu-An 8559
Purpose: To evaluate efficacy of radiofrequency ablation (RFA) in treating colorectal cancer patients with liver metastases. Methods: During January 2010 to April 2012, 56 colorectal cancer patients with liver metastases underwent RFA. CT scans were obtained one month after RFA for all patients to evaluate tumor response. (CR+PR+SD)/n was used to count the disease control rates (DCR). Survival data of 1, 2 and 3 years were obtained from follow up. Results: Patients were followed for 10 to 40 months after RFA (mean time,$25{\pm}10months$ ). Median survival time was 27 months. The 1, 2, 3 year survival rate were 80.4%, 71.4%, 41%, 1 % respectively. 3-year survival time for patients with CR or PR after RFA was 68.8% and 4.3% respectively, the difference was statistically significant. The number of CR, PR, SD and PD in our study was 13, 23, 11 and 9 respectively. Conclusions: RFA could be an effective method for treating colorectal cancer patients with liver metastases, and prolong survival time, especially for metastatic lesions less than or equal to 3 cm. But this result should be confirmed by randomized controlled studies. -
Nourazarian, Seyed Manuchehr;Nourazarian, Alireza;Majidinia, Maryam;Roshaniasl, Elmira 8563
Colorectal cancer is one of the most common lethal cancer types worldwide. In recent years, widespread and large-scale studies have been done on medicinal plants for anti-cancer effects, including Glycyrrhiza glabra. The aim of this study was to evaluate the effects of an ethanol extract Glycyrrhiza glabra on the expression of HSP90, growth and apoptosis in the HT-29 colon cancer cell line. HT-29 cells were treated with different concentrations of extract (50,100,150, and$200{\mu}g/ml$ ). For evaluation of cell proliferation and apoptosis, we used MTT assay and flow cytometry technique, respectively. RT-PCR was also carried out to evaluate the expression levels of HSP90 genes. Results showed that Glycyrrhiza glabra inhibited proliferation of the HT-29 cell line at a concentration of$200{\mu}g/ml$ and this was confirmed by the highest rate of cell death as measured by trypan blue and MTT assays. RT-PCR results showed down-regulation of HSP90 gene expression which implied an ability of Glycyrrhiza glabra to induce apoptosis in HT-29 cells and confirmed its anticancer property. Further studies are required to evaluate effects of the extract on other genes and also it is necessary to make an extensive in vivo biological evaluation and subsequently proceed with clinical evaluations. -
Baghestani, Ahmad Reza;Moghaddam, Sahar Saeedi;Majd, Hamid Alavi;Akbari, Mohammad Esmaeil;Nafissi, Nahid;Gohari, Kimiya 8567
Background: The Cox model is known as one of the most frequently-used methods for analyzing survival data. However, in some situations parametric methods may provide better estimates. In this study, a Weibull parametric model was employed to assess possible prognostic factors that may affect the survival of patients with breast cancer. Materials and Methods: We studied 438 patients with breast cancer who visited and were treated at the Cancer Research Center in Shahid Beheshti University of Medical Sciences during 1992 to 2012; the patients were followed up until October 2014. Patients or family members were contacted via telephone calls to confirm whether they were still alive. Clinical, pathological, and biological variables as potential prognostic factors were entered in univariate and multivariate analyses. The log-rank test and the Weibull parametric model with a forward approach, respectively, were used for univariate and multivariate analyses. All analyses were performed using STATA version 11. A P-value lower than 0.05 was defined as significant. Results: On univariate analysis, age at diagnosis, level of education, type of surgery, lymph node status, tumor size, stage, histologic grade, estrogen receptor, progesterone receptor, and lymphovascular invasion had a statistically significant effect on survival time. On multivariate analysis, lymph node status, stage, histologic grade, and lymphovascular invasion were statistically significant. The one-year overall survival rate was 98%. Conclusions: Based on these data and using Weibull parametric model with a forward approach, we found out that patients with lymphovascular invasion were at 2.13 times greater risk of death due to breast cancer. -
Zhang, Jun;Yao, Yu-Feng;Zha, Xiao-Ming;Pan, Li-Qun;Bian, Wei-He;Tang, Jin Hai 8573
Background: This study was guided by principles of the theoretical system of evidence-based medicine. In particular, when searching for evidence of breast cancer, a measuring scale is an instrument for evaluating curative effects in accordance with the laws and characteristics of medicine and exploring the establishment of a system for medically assessing curative effects. At present, there exist few tools for evaluating curative effects. Patient-reported outcomes (PROs) refer to outcomes directly reported by patients (without input or explanations from doctors or other intermediaries) with respect to all aspects of their health. Data obtained from PROs provide evidence of treatment effects. Materials and Methods: In accordance with the tenets of theoretical medicine and ancient medical theory regarding breast cancer, principles for developing a PRO scale were established, and a theoretical model was developed and a literature review was performed, items from this pool were combined and split, and an initial scale was constructed. After a pilot survey and additional modifications, a pre-questionnaire scale was formed and used in a field investigation. After the application of statistical methods, the item pool was used to create a formal scale. The reliability, validity and feasibility of this formal scale were then assessed. Results: In a clinical investigation, 479 responses were recovered, with an acceptance rate of 95%. a combination of various methods was employed, and the items that were selected by all methods or more than half of the methods were employed in the questionnaire. In these cases, the screening methods were combined with certain features of the item, A total of four domains and 38 items were reserved. The reliability analysis indicated that the PRO scale was relatively reliable. Conclusions: Scientific assessment proved that the proposed scale exhibited good reliability and validity. This scale was readily accepted and could be used to assess the curative effects of medical therapy. However, given the limited scope of this investigation, the capacity for adapting this scale to incorporate other theories could not be determined. -
Shafik, Noha M;Mohamed, Dareen A;Bedder, Asmaa E;El-Gendy, Ahmed M 8579
Background: The molecular mechanisms linking breast cancer progression and inflammation still remain obscure. The aim of the present study was to investigate the possible association of angiopoeitin like protein 4 (ANGPTL4) and its regulatory factor, hypoxia inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$ ), with the inflammatory markers nuclear factor kappa B/p65 (NF-${\kappa}B$ /P65) and interleukin-1 beta (IL-$1{\beta}$ ) in order to evaluate their role in inflammation associated breast cancer progression. Materials and Methods: Angiopoietin-like protein 4 (ANGPTL4) mRNA expressions were evaluated using quantitative real time PCR and its protein expression by immunohistochemistry. DNA binding activity of NF-${\kappa}B$ /P65 was evaluated by transcription factor binding immunoassay. Serum levels of ANGPTL4, HIF-$1{\alpha}$ and IL-$1{\beta}$ were immunoassayed. Tumor clinico-pathological features were investigated. Results: ANGPTL4 mRNA expressions and serum levels were significantly higher in high grade breast carcinoma ($1.47{\pm}0.31$ and$184.98{\pm}18.18$ , respectively) compared to low grade carcinoma ($1.21{\pm}0.32$ and$171.76{\pm}7.58$ , respectively) and controls ($0.70{\pm}0.02$ and$65.34{\pm}6.41$ , respectively), (p<0.05). Also, ANGPTL4 high/moderate protein expression was positively correlated with tumor clinico-pathological features. In addition, serum levels of HIF-$1{\alpha}$ and IL-$1{\beta}$ as well as NF-${\kappa}B$ /P65 DNA binding activity were significantly higher in high grade breast carcinoma ($148.54{\pm}14.20$ ,$0.79{\pm}0.03$ and$247.13{\pm}44.35$ respectively) than their values in low grade carcinoma ($139.14{\pm}5.83$ ,$0.34{\pm}0.02$ and$184.23{\pm}37.75$ , respectively) and controls ($33.95{\pm}3.11$ ,$0.11{\pm}0.02$ and$7.83{\pm}0.92$ , respectively), (p<0.001). Conclusion: ANGPTL4 high serum levels and tissue expressions in advanced grade breast cancer, in addition to its positive correlation with tumor clinico-pathological features and HIF-$1{\alpha}$ could highlight its role as one of the signaling factors involved in breast cancer progression. Moreover, novel correlations were found between ANGPTL4 and the inflammatory markers, IL-$1{\beta}$ and NF-${\kappa}B$ /p65, in breast cancer, which may emphasize the utility of these markers as potential tools for understanding interactions for axes of carcinogenesis and inflammation contributed for cancer progression. It is thus hoped that the findings reported here would assist in the development of new breast cancer management strategies that would promote patients' quality of life and ultimately improve clinical outcomes. However, large-scale studies are needed to verify these results. -
Background: Liver cancer is one of the most common causes of death in the world. In Korea, hepatitis B virus (HBV) is a major risk factor for liver cancer but infection rates have been declining since the implementation of the national vaccination program. In this study, we examined the secular trends in liver cancer mortality to distinguish the effects of age, time period, and birth cohort. Materials and Methods: Data for the annual number of liver cancer deaths in Korean adults (30 years and older) were obtained from the Korean Statistical Information Service for the period from 1984-2013. Joinpoint regression analysis was used to study the shapes of and to detect the changes in mortality trends. Also, an age-period-cohort model was designed to study the effect of each age, period, and birth cohort on liver cancer mortality. Results: For both men and women, the age-standardized mortality rate for liver cancer increased from 1984 to 1993 and decreased thereafter. The highest liver cancer mortality rate has shifted to an older age group in recent years. Within the same birth cohort group, the mortality rate of older age groups has been higher than in the younger age groups. Age-period-cohort analysis showed an association with a high mortality rate in the older age group and in recent years, whereas a decreasing mortality rate were observed in the younger birth cohort. Conclusions: This study confirmed a decreasing trend in liver cancer mortality among Korean men and women after 1993. The trends in mortality rate may be mainly attributed to cohort effects.
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Amoli, Amir hossein Javan;Maserat, Elham;Safdari, Reza;Zali, Mohammad Reza 8595
Background: Decision making modalities for screening for many cancer conditions and different stages have become increasingly complex. Computer-based risk assessment systems facilitate scheduling and decision making and support the delivery of cancer screening services. The aim of this article was to survey electronic risk assessment system as an appropriate tool for the prevention of cancer. Materials and Methods: A qualitative design was used involving 21 face-to-face interviews. Interviewing involved asking questions and getting answers from exclusive managers of cancer screening. Of the participants 6 were female and 15 were male, and ages ranged from 32 to 78 years. The study was based on a grounded theory approach and the tool was a semi-structured interview. Results: Researchers studied 5 dimensions, comprising electronic guideline standards of colorectal cancer screening, work flow of clinical and genetic activities, pathways of colorectal cancer screening and functionality of computer based guidelines and barriers. Electronic guideline standards of colorectal cancer screening were described in the s3 categories of content standard, telecommunications and technical standards and nomenclature and classification standards. According to the participations' views, workflow and genetic pathways of colorectal cancer screening were identified. Conclusions: The study demonstrated an effective role of computer-guided consultation for screening management. Electronic based systems facilitate real-time decision making during a clinical interaction. Electronic pathways have been applied for clinical and genetic decision support, workflow management, update recommendation and resource estimates. A suitable technical and clinical infrastructure is an integral part of clinical practice guidline of screening. As a conclusion, it is recommended to consider the necessity of architecture assessment and also integration standards. -
Ovarian cancer is the main cause of mortality in gynecological malignancy and extensive studies have been conducted to study the underlying molecular mechanisms. The BRCA2 gene is known to be an important tumor suppressor in ovarian cancer, thereby BRCA2 alterations may lead to cancer progression. However, the BRCA2 gene is rarely mutated, and loss of function is suspected to be mediated by epigenetic regulation. In this study we investigated the methylation status and gene expression of BRCA2 in ovarian cancer patients. Ovarian cancer pateints (n=69) were recruited and monitored for 54 months in this prospective cohort study. Clinical specimens were used to study the in situ expression of aberrant BRCA2 proteins and the methylation status of BRCA2. These parameters were then compared with clinical parameters and overall survival rate. We found that BRCA2 methylation was found in the majority of cases (98.7%). However, the methylation status was not associated with protein level expression of BRCA2 (49.3%). Therefore in addition to DNA methylation, other epigenetic mechanisms may regulate BRCA2 expresison. Our findings may become evidence of BRCA2 inactivation mechanism through DNA methylation in the Indonesian population. More importantly, from multivariate analysis, BRCA2 expression was correlated with better overall survival (HR 0.32; p=0.05). High percentage of BRCA2 methylation and correlation of BRCA2 expression with overall survival in epithelial ovarian cancer cases may lead to development of treatment modalities specifically to target methylation of BRCA genes.
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The reliability of using diagnostic binary ratios of particulate carcinogenic polycyclic aromatic hydrocarbons (PAHs) as chemical tracers for source characterisation was assessed by collecting PM10 samples from various air quality observatory sites in Thailand. The major objectives of this research were to evaluate the effects of day and night on the alterations of six different PAH diagnostic binary ratios: An/(An + Phe), Fluo/(Fluo + Pyr), B[a]A/(B[a]A + Chry), B[a]P/(B[a]P + B[e]P), Ind/(Ind + B[g,h,i]P), and B[k]F/Ind, and to investigate the impacts of site-specific conditions on the alterations of PAH diagnostic binary ratios by applying the concept of the coefficient of divergence (COD). No significant differences between day and night were found for any of the diagnostic binary ratios of PAHs, which indicates that the photodecomposition process is of minor importance in terms of PAH reduction. Interestingly, comparatively high values of COD for An/(An + Phe) in PM10 collected from sites with heavy traffic and in residential zones underline the influence of heterogeneous reactions triggered by oxidising gaseous species from vehicular exhausts. Therefore, special attention must be paid when interpreting the data of these diagnostic binary ratios, particularly for cases of low-molecular-weight PAHs.
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Tangkittikasem, Natthakan;Boonyaarunnate, Thiraphon;Aswakul, Pitulak;Kachintorn, Udom;Prachayakul, Varayu 8613
Background: The symptoms of small bowel malignancies are mild and frequently nonspecific, thus patients are often not diagnosed until the disease is at an advanced stage. Moreover, the lack of sufficient studies and available data on small bowel cancer makes diagnosis difficult, further delaying proper treatment for these patients. In fact, only a small number of published studies exist, and there are no studies specific to Thailand. Radiologic and endoscopic studies and findings may allow physicians to better understand the disease, leading to earlier diagnosis and improved patient outcomes. Objective: To retrospectively analyze the clinical, radiologic, and endoscopic characteristics of small bowel cancer patients in Thailand's Siriraj Hospital. Materials and Methods: This retrospective analysis included 185 adult patients (97 men, 88 women; mean age =$57.6{\pm}14.9$ ) with pathologically confirmed small bowel cancer diagnosed between January 2006 and December 2013. Clinical, radiologic, and endoscopic findings were collected and compared between each subtype of small bowel cancer. Results: Of the 185 patients analyzed, gastrointestinal stromal tumor (GIST) was the most common diagnosis (39.5%, n=73). Adenocarcinoma was the second most common (25.9%, n = 48), while lymphoma and all other types were identified in 24.3% (n = 45) and 10.3% (n = 19) of cases, respectively. The most common symptoms were weight loss (43.2%), abdominal pain (38.4%), and upper gastrointestinal bleeding (23.8%). Conclusions: Based on radiology and endoscopy, this study revealed upper gastrointestinal bleeding, an intra-abdominal mass, and a sub-epithelial mass as common symptoms of GIST. Obstruction and ulcerating/circumferential masses were findicative of adenocarcinoma, as revealed by radiology and endoscopy, respectively. Finally, no specific symptoms were related to lymphoma. -
Zadeh, Hossein Ghayoumi;Haddadnia, Javad;Ahmadinejad, Nasrin;Baghdadi, Mohammad Reza 8619
Background: Breast cancer is a common disorder in women, constituting one of the main causes of death all over the world. The purpose of this study was to determine the diagnostic value of the breast tissue diseases by the help of thermography. Materials and Methods: In this paper, we applied non-contact infrared camera, INFREC R500 for evaluating the capabilities of thermography. The study was conducted on 60 patients suspected of breast disease, who were referred to Imam Khomeini Imaging Center. Information obtained from the questionnaires and clinical examinations along with the obtained diagnostic results from ultrasound images, biopsies and thermography, were analyzed. The results indicated that the use of thermography as well as the asymmetry technique is useful in identifying hypoechoic as well as cystic masses. It should be noted that the patient should not suffer from breast discharge. Results: The accuracy of asymmetry technique identification is respectively 91/89% and 92/30%. Also the accuracy of the exact location of identification is on the 61/53% and 75%. The approach also proved effective in identifying heterogeneous lesions, fibroadenomas, and intraductal masses, but not ISO-echoes and calcified masses. Conclusions: According to the results of the investigation, thermography may be useful in the initial screening and supplementation of diagnostic procedures due to its safety (its non-radiation properties), low cost and the good recognition of breast tissue disease. -
Wang, Min;Wu, Wei-Dong;Chen, Gui-Ming;Chou, Sheng-Long;Dai, Xue-Ming;Xu, Jun-Ming;Peng, Zhi-Hai 8625
Background: Central lymph node metastasis(CLNM) is common in papillary thyroid microcarcinoma (PTMC). The aim of this study was to define the pathohistologic risk grading based on surgical outcomes. Materials and Methods: Statistical analysis was performed to figure out the optimal cut-off values of size in preoperative ultrasound images for defining the risk of CLNM in papillary thyroid microcarcinoma. Receiver operating characteristic curves (ROC) studies were carried out to determine the cutoff value(s) for the predictor(s). All the patients were divided into two groups according to the above size and the clinic-pathological and immunohistochemical parameters were compared to determine the significance of findings. Results: The optimal cut-off value of tumor size to predict the risk of CLNM in papillary thyroid microcarcinoma was 0.575 cm (area under the curve 0.721) according to the ROC curves. Significant differences were observed on the multifocality, extrathyroidal extension and central lymph node metastasis between two groups which were divided according to the tumor size by the cutoff values. Patients in two groups showed different positive rate and intensity of Ki67. Conclusions: The size of PTMC in ultrasound images are helpful to predict the aggressiveness of the tumors, it could be an easy predictor for PTMC prognosis and assist us to choose treatment. -
Background: Primary idiopathic myelofibrosis (PMF) is a clonal Philadelphia chromosome-negative myeloproliferative neoplasm characterized by extramedullary hematopoiesis and marrow fibrosis. It is an uncommon hematopoietic malignancy which primarily affects elderly individuals. The rational of this study was to determine its clinico-epidemiological profile along with risk stratification in Pakistani patients. Materials and Methods: In this retrospective cross sectional study, 20 patients with idiopathic myelofibrosis were enrolled from January 2011 to December 2014. Data were analyzed with SPSS version 22. Results: The mean age was
$57.9{\pm}16.5years$ with 70% of patients aged above 50. The male to female ratio was 3:1. Overall only 10% of patients were asymptomatic and the remainder presented with constitutional symptoms. In symptomatic patients, major complaints were weakness (80%), weight loss (75%), abdominal discomfort (60%), night sweats (13%), pruritus (5%) and cardiovascular accidents (5%). Physical examination revealed splenomegaly as a predominant finding detected in 17 patients (85%) with the mean splenic span of$22.2{\pm}2.04cm$ . The mean hemoglobin was$9.16{\pm}2.52g/dl$ with the mean MCV of$88.2{\pm}19.7fl$ . The total leukocyte count of$17.6{\pm}19.2{\times}10^9/l$ and platelets count were$346.5{\pm}321.9{\times}10^9/l$ . Serum lactate dehydrogenase, serum creatinine and uric acid were$731.0{\pm}154.1$ ,$0.82{\pm}0.22$ and$4.76{\pm}1.33$ respectively. According to risk stratification, 35% were in high risk, 40% in intermediate risk and 25% in low risk groups. Conclusions: The majority of PMF patients were male and presented with constitutional symptoms in our setting. Risk stratification revealed predominance of advanced disease in our series. -
Zhao, Shuang;Chen, Shuang-Shuang;Gu, Yuan;Jiang, En-Ze;Yu, Zheng-Hong 8633
Background: To investigate the expression of insulin-like growth factor-I receptor (IGF-IR) and sushi domain containing protein 3 (SUSD3) in breast cancer tissue, and analyze their relationship with clinical parameters and the correlation between the two proteins. Materials and Methods: The expression of IGF-IR and SUSD3 in 100 cases of breast cancer tissues and adjacent normal breast tissues after surgery was detected by immunohistochemical technique MaxVisionTM, and the relationship with clinical pathological features was further analyzed. Results: The positive rate of IGF-IR protein was 86.0% in breast cancer, higher than 3.0% in adjacent normal breast tissue (P<0.05). The positive expression rate of SUSD3 protein was 78.0% in breast cancer, higher than 2.0% in adjacent normal breast tissue (P<0.05). The expression of IGF-IR and SUSD3 was related to estrogen receptor and pathological types (P<0.05),but not with age, stage, the expression of HER-2 and Ki-67 (P>0. 05). The expression of IGF-IR and SUSD3 in breast cancer tissue was positively related (r=0.553, P<0.01). Conclusions: The expression of IGF-IR and SUSD3 may be correlated to the occurrence and development of breast cancer. The combined detection of IGF-IR, SUSD3 and ER may play an important role in judging prognosis and guiding adjuvant therapy after surgery of breast cancer. -
Liang, Rong;Xie, Hai-Ying;Lin, Yan;Li, Qian;Yuan, Chun-Ling;Liu, Zhi-Hui;Li, Yong-Qiang 8637
Background: Malignant serous effusions (MSE) are one complication in patients with advanced cancer. Endostar is a new anti-tumor drug targeting vessels which exerts potent inhibition of neovascularization. This study aimed to systematically evaluate the efficacy and safety of intraperitoneal perfusion therapy of Endostar combined with platinum chemotherapy for malignant serous effusions (MSE). Materials and Methods: Randomized controlled trials (RCTs) on intraperitoneal perfusion therapy of Endostar combined with platinum chemotherapy for malignant serous effusions were searched in the electronic data of PubMed, EMBASE, Web of Science, CNKI, VIP, CBM and WanFang. The quality of RCTs was evaluated by two independent researchers and a meta-analysis was performed using RevMan 5.3 software. Results: The total of 25 RCTs included in the meta-analysis covered 1,253 patients, and all literature quality was evaluated as "B" grade. The meta-analysis showed that Endostar combined with platinum had an advantage over platinum alone in terms of response rate of effusions (76% vs 48%, RR=1.63, 95%CI: 1.50-1.78, P<0.00001) and improvement rate in quality of life (69% vs 44%, RR=1.57, 95%CI: 1.42-1.74, P<0.00001). As for safety, there was no significant difference between the two groups in the incidences of nausea and vomiting (35% vs 34%, RR=1.01, 95%CI: 0.87-1.18, P=0.88), leucopenia (38% vs 38%, RR=1, 95%CI: 0.87-1.15, P=0.99), and renal impairment (18% vs 20%, RR=0.86, 95%CI: 0.43-1.74, P=0.68). Conclusions: Endostar combined with platinum by intraperitoneal perfusion is effective for malignant serous effusions, and patient quality of life is significantly improved without the incidence of adverse reactions being obviously increased. -
Background: Consumption of tobacco in the form of a water pipe has recently increased, especially among young people. This study aimed to develop a scale which would be used in order to detect perceptions about the effects of water pipe smoking on health and to test its validity and reliability. Our scale named "a scale of perception about the effects of water pipe smoking on health" was developed in order to detect factors effecting the perception of adolescents about the effects of water pipe smoking on health. Materials and Methods: The sample consisted of 150 voluntary students in scale development and 750 voluntary students in the study group. Data were collected via a questionnaire prepared by researchers themselves and 5-pont Likert scale for "a scale of perception about the effects of water pipe smoking on health" which was prepared through the literature. Data evaluation was carried out on a computer with SPSS. Results: The findings of the study showed that "a scale of perception about the effects of water pipe smoking on health" was valid and reliable. Total score average of the adolescents participated in the study was
$58.5{\pm}1.25$ . The mean score of the ones who did not smoke water pipe ($60.1{\pm}11.7$ ) was higher than the mean score of the ones who smoked water pipe ($51.6{\pm}13.8$ ), the difference being statistically significant. Conclusions: It is established that "a scale of perception about the effects of water pipe smoking on health" was a reliable and valid measurement tool. It is also found out that individuals who smoked a water pipe had a lower level of perception of water pipe smoking effects on health than their counterparts who did not smoke a water pipe. -
Li, Hai-Long;Gu, Jing;Wu, Jian-Jun;Ma, Chun-Lin;Yang, Ya-Li;Wang, Hu-Ping;Wang, Jing;Wang, Yong;Chen, Che;Wu, Hong-Yan 8653
Background: Heparanase is believed to be involved in gastric carcinogenesis. However, the clinicopathologic features of gastric cancer with high heparanase expression remain unclear. Aim : The purpose of this study was to comprehensively and quantitatively summarize available evidence for the use of heparanase mRNA and protein expression to evaluate the clinicopathological associations in gastric cancer in Asian patients by meta-analysis. Materials and Methods: Relevant articles listed in MEDLINE, CNKI and the Cochrane Library databases up to MARCH 2015 were searched by use of several keywords in electronic databases. A meta-analysis was performed to clarify the impact of heparanase mRNA and protein on clinicopathological parameters in gastric cancer. Combined ORs with 95%CIs were calculated by Revman 5.0, and publication bias testing was performed by stata12.0. Results: A total of 27 studies which included 3,891 gastric cancer patients were combined in the final analysis. When stratifying the studies by the pathological variables of heparanase mRNA expression, the depth of invasion (633 patients) (OR=4.96; 95% CI=2.38-1.37; P<0.0001), lymph node metastasis (639 patients) (OR=6.22; 95%CI=2.70-14.34, P<0.0001), and lymph node metastasis (383 patients) (OR=6.85; 95% CI=2.04-23.04; P=0.002) were all significant. When stratifying the studies by the pathological variables of heparanase protein expression, this was the case for depth of invasion (1250 patients) (OR=2.76; 95% CI=1.52-5.03; P=0.0009), lymph node metastasis (1178 patients) (OR=4.79 ; 95% CI=3.37-6.80, P<0.00001), tumor size (727 patients) (OR=2.06 ; 95% CI=1.31-3.23; P=0.002) (OR=2.61; 95% CI=2.09-3.27; P=0.000), and TNM stage (1233 patients) (OR=6.85; 95% CI=2.04-23.04; P=0.002). Egger's tests suggested publication bias for depth of invasion, lymph node metastasis, lymph node metastasis and tumor size of heparanase mRNA and protein expression. Conclusions: This meta-analysis suggests that higher heparanase expression in gastric cancer is associated with clinicopathologic features of depth of invasion, lymph node metastasis and TNM stage at mRNA and protein levels, and of tumor size only at the protein level. Egger's tests suggested publication bias for these clinicopathologic features of heparanase mRNA and protein expression, and which may be caused by shortage of relevant studies. As a result, although abundant reports showed heparanase may be associated with clinicopathologic features in gastric cancer, this meta-analysis indicates that more strict studies were needed to evaluate its clinicopathologic significance. -
Pun, Chin Bahadur;Pradhananga, Kishore K;Siwakoti, Bhola;Subedi, Krishna;Moore, Malcolm A 8659
In Nepal, while no population based cancer registry program exists to assess the incidence, prevalence, morbidity and mortality of cancer, at the national level a number of hospital based cancer registries are cooperating to provide relevant data. Seven major cancer diagnosis and treatment hospitals are involved, including the BP Koirala Memorial Cancer hospital, supported by WHO-Nepal since 2003. The present retrospective analysis of cancer patients of all age groups was conducted to assess the frequencies of different types of cancer presenting from January 1st to December 31st 2012. A total of 7,212 cancer cases were registered, the mean age of the patients being 51.9 years. The most prevalent age group in males was 60-64 yrs (13.6%), while in females it was 50-54 yrs (12.8%). The commonest forms of cancer in males were bronchus and lung (17.6%) followed by stomach (7.3%), larynx (5.2%) and non Hodgkins lymphoma (4.5%). In females, cervix uteri (19.1%) and breast (16.3%), were the top ranking cancer sites followed by bronchus and lung (10.2%), ovary (6.1%) and stomach (3.8%). The present data provide an update of the cancer burden in Nepal and highlight the relatively young age of breast and cervical cancer patients. -
Li, Xing;Zhong, Xiang;Chen, Zhan-Hong;Wang, Tian-Tian;Ma, Xiao-Kun;Xing, Yan-Fang;Wu, Dong-Hao;Dong, Min;Chen, Jie;Ruan, Dan-Yun;Lin, Ze-Xiao;Wen, Jing-Yun;Wei, Li;Wu, Xiang-Yuan;Lin, Qu 8665
Background and Aims: Hepatitis B virus (HBV) reactivation was reported to be induced by transcatheter arterial chemoembolization (TACE) in HBV-related hepatocellular carcinonma (HCC) patients with a high incidence. The effective strategy to reduce hepatitis flares due to HBV reactivation in this specific group of patients was limited to lamivudine. This retrospective study was aimed to investigate the efficacy of prophylactic entecavir in HCC patients receiving TACE. Methods: A consecutive series of 191 HBV-related HCC patients receiving TACE were analyzed including 44 patients received prophylactic entecavir. Virologic events, defined as an increase in serum HBV DNA level to more than 1 log10 copies/ml higher than nadir the level, and hepatitis flares due to HBV reactivation were the main endpoints. Results: Patients with or without prophylactic were similar in host factors and the majorities of characteristics regarding to tumor factors, HBV status, liver function and LMR. Notably, cycles of TACE were parallel between the groups. Ten (22.7%) patients receiving prophylactic entecavir reached virologic response. The patients receiving prophylactic entecavir presented significantly reduced virologic events (6.8% vs 54.4%, p=0.000) and hepatitis flares due to HBV reactivation (0.0% vs 11.6%, p=0.039) compared with patients without prophylaxis. Kaplan-Meier analysis illustrated that the patients in the entecavir group presented significantly improved virologic events free survival (p=0.000) and hepatitis flare free survival (p=0.017). Female and Eastern Cooperative Oncology Group (ECOG) performance status 2 was the only significant predictors for virological events in patients without prophylactic antiviral. Rescue antiviral therapy did not reduce the incidence of hepatitis flares due to HBV reactivation. Conclusion: Prophylactic entecavir presented promising efficacy in HBV-related cancer patients receiving TACE. Lower performance status and female gender might be the predictors for HBV reactivation in these patients. -
Sasidharan, Sreenivasan;Jothy, Subramanion L;Kavitha, Nowroji;Chen, Yeng;Kanwar, Jagat R 8671
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