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 5
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Riaz, Syeda Kiran;Iqbal, Yasmeen;Malik, Muhammad Faraz Arshad 1677
Cancer progression is attained by uncontrolled cell division and metastasis. Increase in tumor size triggers different vascular channel formation to address cell nutritional demands. These channels are responsible for transferring of nutrients and gaseous to the cancer cells. Cancer vascularization is regulated by numerous factors including vascular endothelial growth factors (VEGFs). These factors play an important role during embryonic development. Members included in this group are VEGFA, VEGFB, VEGFC, PIGF and VEGFD which markedly influence cellular growth and apoptosis. Being freely diffusible these proteins act in both autocrine and paracrine fashions. In this review, genetic characterization these molecules and their putative role in cancer staging has been elaborated. Prognostic significance of these molecules along with different stages of cancer has also been summarized. Brief outline of ongoing efforts to target hot spot target sites against these VEGFs and their cognate limitations for therapeutic implications are also highlighted. -
Islamian, Jalil Pirayesh;Hatamian, Milad;Rashidi, Mohammad Reza 1683
Different types of treatment are available for patients with breast cancer, the most being radiotherapy, chemotherapy, hormonal therapy and combination therapy. Recently, nanoparticles have been emerging as promising agents for cancer therapy and are being investigated as contrast agents, drug carriers, radiosensitizers and also for hyperthermia effects. In this review the focus is on approaches for targeted treatment of breast cancer by combining nanoparticles, chemodrugs and radiation. The availble data suggest the possibility of increased roles for combined therapy, particularly by reducing the dose of each treatment modality, and consequently minimizing related side effects. -
Nasopharyngeal carcinoma is an endemic disease within specific regions in the world. Radiotherapy is the main treatment. In recent decades, intensity-modulated radiation therapy has undergone a rapid evolution. Compared with two-dimensional radiotherapy and/or three-dimensional conformal radiotherapy, evidence has shown it may improve quality of life and prognosis for patients with nasopharyngeal carcinoma. In addition, helical tomotherapy is an emerging technology of intensity-modulated radiation therapy. Its superiority in dosimetric and clinical outcomes has been demonstrated when compared to traditional intensity-modulated radiation therapy. However, many challenges need to be overcome for intensity-modulated radiation therapy of nasopharyngeal carcinoma in the future. Issues such as the status of concurrent chemotherapy, updating of target delineation, the role of replanning during IMRT, the causes of the main local failure pattern require settlement. The present study reviews traditional intensity-modulated radiation therapy, helical tomotherapy, and new challenges in the management of nasopharyngeal carcinoma.
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The heterogeneous nature of lung cancer has become increasingly apparent since introduction of molecular classification. In general, advanced lung cancer is an aggressive malignancy with a poor prognosis. Activating alterations in several potential driver oncogenic genes have been identified, including EGFR, ROS1 and ALK and understanding of their molecular mechanisms underlying development, progression, and survival of lung cancer has led to the design of personalized treatments that have produced superior clinical outcomes in tumours harbouring these mutations. In light of the tsunami of new biomarkers and targeted agents, next generation sequencing testing strategies will be more appropriate in identifying the patients for each therapy and enabling personalized patients care. The challenge now is how best to interpret the results of these genomic tests, in the context of other clinical data, to optimize treatment choices. In genomic era of cancer treatment, the traditional one-size-fits-all paradigm is being replaced with more effective, personalized oncologic care. This review provides an overview of lung cancer genomics and personalized treatment.
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Ulas, Arife;Silay, Kamile;Akinci, Sema;Dede, Didem Sener;Akinci, Muhammed Bulent;Sendur, Mehmet Ali Nahit;Cubukcu, Erdem;Coskun, Hasan Senol;Degirmenci, Mustafa;Utkan, Gungor;Ozdemir, Nuriye;Isikdogan, Abdurrahman;Buyukcelik, Abdullah;Inanc, Mevlude;Bilici, Ahmet;Odabasi, Hatice;Cihan, Sener;Avci, Nilufer;Yalcin, Bulent 1699
Background: Medication errors in oncology may cause severe clinical problems due to low therapeutic indices and high toxicity of chemotherapeutic agents. We aimed to investigate unintentional medication errors and underlying factors during chemotherapy preparation and administration based on a systematic survey conducted to reflect oncology nurses experience. Materials and Methods: This study was conducted in 18 adult chemotherapy units with volunteer participation of 206 nurses. A survey developed by primary investigators and medication errors (MAEs) defined preventable errors during prescription of medication, ordering, preparation or administration. The survey consisted of 4 parts: demographic features of nurses; workload of chemotherapy units; errors and their estimated monthly number during chemotherapy preparation and administration; and evaluation of the possible factors responsible from ME. The survey was conducted by face to face interview and data analyses were performed with descriptive statistics. Chi-square or Fisher exact tests were used for a comparative analysis of categorical data. Results: Some 83.4% of the 210 nurses reported one or more than one error during chemotherapy preparation and administration. Prescribing or ordering wrong doses by physicians (65.7%) and noncompliance with administration sequences during chemotherapy administration (50.5%) were the most common errors. The most common estimated average monthly error was not following the administration sequence of the chemotherapeutic agents (4.1 times/month, range 1-20). The most important underlying reasons for medication errors were heavy workload (49.7%) and insufficient number of staff (36.5%). Conclusions: Our findings suggest that the probability of medication error is very high during chemotherapy preparation and administration, the most common involving prescribing and ordering errors. Further studies must address the strategies to minimize medication error in chemotherapy receiving patients, determine sufficient protective measures and establishing multistep control mechanisms. -
Khabaz, Mohamad Nidal;Gari, Mamdooh Abdullah;Al-Maghrabi, Jaudah Ahmed;Nedjadi, Taoufik;Bakarman, Marwan 1707
Eighty six cases of invasive ductal breast carcinomas were utilized to investigate GSTP1 polymorphisms in certain immunohistochemistry (IHC) subtypes of breast cancer with respect to ER, PR and HER2 expression. The frequency of wild allele homozygote, heterozygote and variant allele homozygote genotypes were 46.5%, 52.3% and 1.16% respectively; Whereas 54.3% of the control subjects were GSTP1 wild type allele homozygous, 40.0% were heterozygous and 5.71% mutant allele homozygous. There was dramatic inverted relation between positive IHC ER staining and increasing grade of tumors in general (100%, 88.6%, 40.4%) and especially among tumors with heterozygote genotype of GSTP1 (70%, 35.4%, 22.7). There was increase in positive IHC HER2 staining consistent with higher grades in general (20%, 29.6%, 50.0%), especially among tumors with GSTP1 wild allele homozygote genotype (5.0%, 9.1%, 31.8%). A remarkable reverse relation was also observed between the fraction of IHC hormone receptor phenotype ER+/PR+/ HER2- and increased grade of tumors (60.0%, 45.5%, and 27.3%) especially among tumors with GSTP1 heterozygote genotype, and a similar link was noted regarding ER+/PR-/ HER2- and tumor grade. There was increase in frequency of ER-/PR-/ HER2- (0.0%, 6.8%, and 18.2%) and ER-/PR-/ HER2+ (0.0%, 4.54%, and 40.9%) consistent with the higher grades of tumors in general and especially GSTP1 heterozygote genotype tumors. As a conclusion, there is no correlation between GSTP1 polymorphism and increased risk of breast cancer i.e. the mutant allele is randomly distributed in cancer and control cases. However, there is a link between GSTP1 genotypes and hormone receptor expression status and certain phenotypes of breast cancer, which may have clinical importance. -
Wang, Hai-Yi;Zhao, Yu-Nian;Wu, Jian-Zhong;Wang, Zheng;Tang, Jing-Hai 1715
Background: Magnetic resonance imaging of breast, reported to be a high sensitivity of 94% to 100%, is the most sensitive method for detection of breast cancer. The purpose of this study was to investigate our clinical experience in MRI-guided breast lesion wire localization in Chinese women. Materials and Methods: A total of 44 patients with 46 lesions undergoing MRI-guided breast lesion localization were prospectively entered into this study between November 2013 and September 2014. Samples were collected using a 1.5-T magnet with a special MR biopsy positioning frame device. We evaluated clinical lesion characteristics on pre-biopsy MRI, pathologic results, and dynamic curve type baseline analysis. Results: Of the total of 46 wire localization excision biopsied lesions carried out in 44 female patients, pathology revealed fourteen malignancies (14/46, 30.4%) and thirty-two benign lesions (32/46, 69.6%). All lesions were successfully localized followed by excision biopsy and assessed for morphologic features highly suggestive of malignancy according to the American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) category of MRI (C4a=18, C4b=17, C4c=8,C5=3). Of 46 lesions, 37 were masses and 9 were non-mass enhancement lesions. Thirty-two lesions showed a continuous kinetics curve, 11 were plateau and 3 were washout. Conclusions: Our study showed success in MRI-guided breast lesion wire localization with a satisfactory cancer diagnosis rate of 30.4%. MRI-guided wire localization breast lesion open biopsy is a safe and effective tool for the workup of suspicious lesions seen on breast MRI alone without major complications. This may contribute to increasing the diagnosis rate of early breast cancer and improve the prognosis in Chinese women. -
Altay, Birsen;Avci, Ilknur Aydin;Rizalar, Selda;Oz, Hatice;Meral, Damla 1719
Background: Breast and cervical cancers are the most common types of cancer in women worldwide. Previous studies in Asia have shown that related knowledge and awareness is low among female university students. The goal of this study was to assess breast and cervical cancer knowledge, practices, and awareness among female university students in Samsun,Turkey. Materials and Methods: This research was a cross-sectional survey of female university students using a self-administered. questionnaire to investigate participant awareness and knowledge of breast and cervical cancer. A total of 301 female university students participated. Descriptive statistics and chi square tests were used for data analysis. Results: The mean age of the participants in this study was$22.0{\pm}5.91$ years. Regarding family history, 89.7 % of the students had no known familial history of breast cancer. Students (65.4%) had knowledge about breast self examination and 52.2 % of them had performed breast self examinationm while 55.1% of them had knowledge about prevention of cervical cancer. Conclusions: Although the results are preliminary, the study points to an insufficient knowledge of university students in Samsun about breast and cervical cancer. -
Hou, Zhi-Hong;Zhao, Wen-Cui;Zhang, Qi;Zheng, Wei 1725
Objective: To explore effects of paclitaxel-loaded poly lactic-co-glycolic acid (PLGA) particles on the viability of human hepatocellular carcinoma (HCC) HepG2 cells. Materials and Methods: The viability of HepG2 cells was assessed using MTT under different concentrations of prepared paclitaxel-loaded particles and paclitaxel (6.25, 12.5, 25, 50, and 100 mg/L), and apoptosis was analyzed using Hochest33342/Annexin V-FITC/PI combined with an IN Cell Analyzer 2000. Results: Paxlitaxel-loaded nanoparticles were characterized by narrow particle size distribution (158.6 nm average particle size). The survival rate of HepG2 cells exposed to paclitaxel-loaded PLGA particles decreased with the increase of concentration and time period (P<0.01 or P<0.05), the dose- and time-dependence indicating sustained release (P<0.05). Moreover, apoptosis of HepG2 cells was induced, again with an obvious dose- and time-effect relationship (P<0.05). Conclusions: Paclitaxel-loaded PLGA particles can inhibit the proliferation and induce the apoptosis of HCC HepG2 cells. This new-type of paclitaxel carrier body is easily made and has low cost, good nanoparticle characterization and sustained release. Hence, paclitaxel-loaded PLGA particles deserve to be widely popularized in the clinic. -
Background: The purpose of this study was to investigate the associations among the internal health locus of control, depression, perceived health status, self efficacy, social support, and health-promoting behavior in Iranian breast cancer survivors and to determine influential variables. Materials and Methods: A predictive design was adopted. By convenient sampling the data of 262 breast cancer survivors in Iran were collected by questionnaires during 2014. Data were analyzed applying descriptive statistics, t-tests, one-way ANOVA, Pearson's correlation coefficients, and stepwise multiple regression. Results: The internal health locus of control, depression, perceived health status, self efficacy, social support and undergoing chemotherapy all correlated significantly with the health-promoting lifestyle. Stepwise multiple regression analysis revealed that social internal health locus of control, depression, perceived health status, self efficacy and social support and chemotherapy accounted for about 39.8% of the variance in health promoting lifestyle. The strongest influence was social support, followed by self efficacy, perceived health status, chemotherapy and depression. Conclusions: The results of the study clarifed the seriousness of social support, self efficacy, perceived health status and depression in determining the health-promoting lifestyle among Iranian breast cancer survivors. Health professionals should concentrate on these variables in designing plans to promoting a healthy lifestyle.
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Muisuk, Kanha;Silsirivanit, Atit;Imtawil, Kanokwan;Bunthot, Suphawadee;Pukhem, Ake;Pairojkul, Chawalit;Wongkham, Sopit;Wongkham, Chaisiri 1737
Background: Mitochondrial DNA (mtDNA) mutations have been shown to be associated with cancer. This study explored whether mtDNA mutations enhance cholangiocarcinoma (CCA) development in individuals. Materials and Methods: The whole mitochondrial genome sequences of 25 CCA patient tissues were determined and compared to those of white blood cells from the corresponding individuals and 12 healthy controls. The mitochondrial genome was amplified using primers from Mitoseq and compared with the Cambridge Reference Sequence. Results: A total of 161 mutations were identified in CCA tissues and the corresponding white blood cells, indicating germline origins. Sixty-five (40%) were new. Nine mutations, representing those most frequently observed in CCA were tested on the larger cohort of 60 CCA patients and 55 controls. Similar occurrence frequencies were observed in both groups. Conclusions: While the correspondence between the cancer and mitochondrial genome mutation was low, it is of interest to explore the functions of the missense mutations in a larger cohort, given the possibility of targeting mitochondria for cancer markers and therapy in the future. -
Zhou, Shao-Bing;Liu, Yang-Chen;Yin, Xiao-Xiang;Ding, Wen-Xiu;Guo, Xin-Wei;Gu, Liang;Huang, Xin-En 1743
Objective: To evaluate the efficacy and adverse effects of three dimensional conformal radiotherapy (3D-CRT) with tamoxifen in treating patients with postoperative malignant glioma. Patients and Methods: 60 patients of postoperative malignant glioma were randomly assigned into two groups, 30 patients were treated with 3D-CRT plus tamoxifen (treatment group), and the other 30 patients with 3D-CRT plus temozolomide (control group). All patients were radiated by 6MV X-ray, 2.0Gy per fraction, once daily, with a total dose (DT) of 56~60Gy. Tamoxifen was delivered at$60mg/m^2/d$ , temozolomide was given at$75mg/m^2/d$ . All patients were treated with concurrent radiotherapy. Results: One, 2, 3 year survival rates of treatment and control group were 63.3%, 30.0%, 23.0% and 70.0%, 33.3%, 26.7%, respectively (${\chi}^2=0.01$ , 0.23, 0.09, P>0.05). The rate of thromboembolism in treatment group was 6.7%. Conclusion: Therapeutic efficacy of two groups was similar, but it was more cost-effective in treatment group, and toxicity did not increase. -
Nun-anan, Pongjarat;Vilaichone, Ratha-korn 1747
Background: Esophageal cancer is one of the major health concerns in Southeast Asian countries, including Thailand. However, only a limited number of studies have been reported from this region. This study was designed to evaluate the prevalence, clinical characteristics and survival rate of esophageal cancer in Thailand. Materials and Methods: Clinical information, histological features and endoscopic findings were collected from a tertiary care center in central region of Thailand between September 2011- November 2014 and reviewed. Results: A total of 64 esophageal cancer patients including 58 men and 6 women with mean age of 62.6 years were enrolled. Common presenting symptoms were dysphagia (74%), dyspepsia (10%) and hematemesis (8%). Mean duration of symptoms prior to diagnosis was 72 days. Esophageal stenosis with contact bleeding was the most common endoscopic finding (55.6%). The location of cancer was found in proximal (16%), middle (50%) and distal (34%) esophagus. Squamous cell carcinoma was far more common histology than adenocarcinoma (84.2% vs 10.5%). However, esophageal adenocarcinoma was significantly more common than squamous cell carcinoma in distal area of esophagus (100% vs 22.9%; p=0.0001, OR=1.6, 95%CI=1.1-2.2). Esophageal cancer stages 3 and 4 accounted for 35.2% and 59.3% respectively. Overall 2-year survival rate was 20% and only 16% in metastatic patients. Conclusions: Most esophageal cancer patients in Thailand have squamous cell carcinoma and nearly all present at advanced stage with a grave prognosis. Screening of high risk individuals and early detection might be important keys to improve the survival rate and treatment outcome in Thailand. -
Deenonpoe, Raksawan;Chomvarin, Chariya;Pairojkul, Chawalit;Chamgramol, Yaowalux;Loukas, Alex;Brindley, Paul J;Sripa, Banchob 1751
There has been a strong, positive correlation between opisthorchiasis-associated cholangiocarcinoma and infection with Helicobacter. Here a rodent model of human infection with Opisthorchis viverrini was utilized to further investigate relationships of apparent co-infections with O. viverrini and H. pylori. A total of 150 hamsters were assigned to five groups: i) Control hamsters not infected with O. viverrini; ii) O. viverrini-infected hamsters; iii) non-O. viverrini infected hamsters treated with antibiotics (ABx); iv) O. viverrini-infected hamsters treated with ABx; and v) O. viverrini-infected hamsters treated both with ABx and praziquantel (PZQ). Stomach, gallbladder, liver, colonic tissue, colorectal feces and O. viverrini worms were collected and the presence of species of Helicobacter determined by PCR-based approaches. In addition, O. viverrini worms were cultured in vitro with and without ABx for four weeks, after which the presence of Helicobacter spp. was determined. In situ localization of H. pylori and Helicobacter-like species was performed using a combination of histochemistry and immunohistochemistry. The prevalence of H. pylori infection in O. viverrini-infected hamsters was significantly higher than that of O. viverrini-uninfected hamsters ($p{\leq}0.001$ ). Interestingly, O. viverrini-infected hamsters treated with ABx and PZQ (to remove the flukes) had a significantly lower frequency of H. pylori than either O. viverr-iniinfected hamsters treated only with ABx or O. viverrini-infected hamsters, respectively ($p{\leq}0.001$ ). Quantitative RT-PCR strongly confirmed the correlation between intensity H. pylori infection and the presence of liver fluke infection. In vitro, H. pylori could be detected in the O. viverrini worms cultured with ABx over four weeks. In situ localization revealed H. pylori and other Helicobacter-like bacteria in worm gut. The findings indicate that the liver fluke O. viverrini in the biliary tree of the hamsters harbors H. pylori and Helicobacter-like bacteria. Accordingly, the association between O. viverrini and H. pylori may be an obligatory mutualism. -
Purpose: To establish the concept of lung cancer hazard assessment theoretical models, evaluating the degree of lung cancer risk of Beijing for regional population lung cancer hazard assessment to provide a basis for technical support. Materials and Methods: ISO standards were used to classify stratified analysis for the entire population, life cycle, processes and socioeconomic management. Associated risk factors were evaluated as lung cancer hazard risk assessment first class indicators. Study design: Using the above materials, indicators were given the weight coefficients, building lung cancer risk assessment theoretical models. Regional data for Beijing were entered into the theoretical model to calculate the parameters of each indicator and evaluate the degree of local lung cancer risk. Results: Adopting the concept of lung cancer hazard assessment and theoretical models for regional populations, we established a lung cancer hazard risk assessment system, including 2 first indicators, 8 secondary indicators and 18 third indicators. All indicators were given weight coefficients and used as information sources. Score of hazard for lung cancer was 84.4 in Beijing. Conclusions: Comprehensively and systematically building a lung cancer risk assessment theoretical model for regional populations in conceivable, evaluating the degree of lung cancer risk of Beijing, providing technical support and scientific basis for interventions for prevention.
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Al-Maweri, Sadeq Ali;Abbas, Alkasem;Tarakji, Bassel;Al-Jamaei, Aisha Saleh;Alaizari, Nader Ahmed;Al-Shamiri, Hashem M 1765
Background: Oral cancer presents with high mortality rates, and the likelihood of survival is remarkably superior when detected early. Health care providers, particularly dentists, play a critical role in early detection of oral cancers and should be knowledgeable and skillful in oral cancer diagnosis. Purpose: The aim of the present study was to assess the current knowledge of future Yemeni dentists and their opinions on oral cancer. Materials and Methods: A pretested self-administered questionnaire was distributed to fourth and fifth year dental students. Questions relating to knowledge of oral cancer, risk factors, and opinions on oral cancer prevention and practices were posed. Results: The response rate was 80%. The vast majority of students identified smoking and smokeless tobacco as the major risk factors for oral cancer. Most of the students (92.6%) knew that squamous cell carcinoma is the most common form of oral cancer, and 85.3% were aware that tongue and floor of the mouth are the most likely sites. While the majority showed willingness to advise their patients on risk factors, only 40% felt adequately trained to provide such advice. More than 85% of students admitted that they need further information regarding oral cancer. As expected, students of the final year appeared slightly more knowledgeable regarding risk factors and clinical features of the disease. Conclusions: The findings of the present study suggest that here is a need to reinforce the undergraduate dental curriculum with regards to oral cancer education, particularly in its prevention and early detection. -
Mitupatum, Thantip;Aree, Kalaya;Kittisenachai, Suthathip;Roytrakul, Sittiruk;Puthong, Songchan;Kangsadalampai, Sasichai;Rojpibulstit, Panadda 1771
Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide. Presently, targeted therapy via monoclonal antibodies to specific tumor-associated antigens is being continuously developed. Hep88 mAb has proven to exert tumoricidal effects on the HepG2 cell via a paraptosis-like morphology. To verify the pathway, we then demonstrated downstream up-regulation of caspase-3, caspase-8 and caspase-9, assessingmRNA expression by real-time PCR and associated enzyme activity by colorimetric assay. Active caspase-3 determination was also accomplished by flow cytometry. Active caspase-3 expression was increased by Hep88 mAb treatment in a dose-and time-dependent manner. All of the results indicated that Hep88 mAb induced programmed cell death in the HepG2 cell line from paraptosis-like to apoptosis by downstream induction of caspases. These conclusions imply that Hep88mAb might be a promising tool for the effective treatment of HCC in the future. -
Li, Hai-Long;Xie, Shou-Pin;Yang, Ya-Li;Cheng, Ying-Xia;Zhang, Ying;Wang, Jing;Wang, Yong;Liu, Da-Long;Chen, Zhao-Feng;Zhou, Yong-Ning;Wu, Hong-Yan 1781
Background: miRNAs are relatively recently discovered cancer biomarkers which have important implications for cancer early diagnosis, treatment and estimation of prognosis. Here we focussed on expression of mir-196a-5p in gastric cancer tissues and cell lines so as to analyse its significance for clinicopathologic characteristics and generate enriched KEGG pathways clustered by target genes for exploring its potential roles as a biomarker in gastric cancer. Materials and Methods: The expression of mir-196a-5p in poorly, moderate and well differentiated gastric cancer cell lines compared with GES-1 was detected by RT-qPCR, and the expression of mir-196a-5p in gastric cancer tissues comparing with adjacent non cancer tissues of 58 cases were also assessed by RT-qPCR. Subsequently, an analysis of clinical significance of mir-196a-5p in gastric cancer and enriched KEGG pathways was executed based on the miRWalk prediction database combined with bioinformatics tools DAVID 6.7 and Mirfocus 3.0. Results: RT-qPCR showed that mir-196a-5p was up-regulated in 6 poorly and moderate differentiated gastric cancer cell lines SGC-7901, MKN-45, MKN-28, MGC-803, BGC-823, HGC-27 compared with GES-1, but down-regulated in the highly differentiated gastric cancer cell line AGS. Clinical data indicated mir-196a-5p to beup-regulated in gastric cancer tissues (47/58). Overexpression of mir-196a-5p was associated with more extensive degree of lymph node metastasis and clinical stage (P < 0.05; x2 test). Enriched KEGG pathway analyses of predicted and validated targets in miRWalk combined with DAVID 6.7 and Mirfocus 3.0 showed that the targeted genes regulated by mir-196a-5p were involved in malignancy associated biology. Conclusions: Overexpression of mir-196a-5p is associated with lymph node metastasis and clinical stage, and enriched KEGG pathway analyses showed that targeted genes regulated by mir-196a-5p may contribute to tumorgenesis, suggesting roles as an oncogenic miRNA biomarker in gastric cancer. -
Sobhonslidsuk, Abhasnee;Pulsombat, Akharawit;Kaewdoung, Piyaporn;Petraksa, Supanna 1789
Background: Non-alcoholic fatty liver disease (NAFLD), the most common liver problem in diabetes, is a risk factor for liver cancer. Diabetes, high body mass index (BMI) and old age can all contribute to NAFLD progression. Transient elastography (TE) is used for non-invasive fibrosis assessment. Objectives: To identify the prevalence of NAFLD and significant hepatic fibrosis in diabetic patients and to assess associated factors. Materials and Methods: One hundred and forty-one diabetic and 60 normal subjects were screened. Fatty liver was diagnosed when increased hepatic echogenicity and vascular blunting were detected by ultrasonography. Liver stiffness measurement (LSM) representing hepatic fibrosis was assessed by TE. LSM${\geq}7$ kPa was used to define significant hepatic fibrosis. Results: Four cases were excluded due to positive hepatitis B viral markers and failed TE. Diabetic patients had higher BMI, systolic blood pressure, waist circumference and fasting glucose levels than normal subjects. Fatty liver was diagnosed in 82 (60.7%) diabetic patients but in none of the normal group. BMI (OR: 1.31; 95%CI: 1.02-1.69; p=0.038) and alanine aminotransferase (ALT)(OR: 1.14; 95%CI: 1.05-1.23; p=0.002) were associated with NAFLD. Diabetic patients with NAFLD had higher LSM than those without [5.99 (2.4) vs 4.76 (2.7) kPa, p=0.005)]. Significant hepatic fibrosis was more common in diabetic patients than in normal subjects [22 (16.1%) vs 1 (1.7%), p=0.002]. Aspartate aminotransferase (AST)(OR: 1.24; 95%CI: 1.07-1.42; p=0.003) was associated with significant hepatic fibrosis. Conclusions: Sixty and sixteen percent of diabetic patients were found to have NAFLD and significant hepatic fibrosis. High BMI and ALT levels are the predictors of NAFLD, and elevated AST level is associated with significant hepatic fibrosis. -
Ozkaraman, Ayse;Culha, Ilkay;Fadiloglu, Zehra Cicek;Kosgeroglu, Nedime;Gokce, Serap;Alparslan, Guler Balci 1795
Background: Breast cancer is one of the most common cancer types in women and is amongst the most devastating and stressful events in the life of women. The external appearance of breast cancer patients usually changes due to the surgical and/or medical therapies used. An association may be found between social support perception and social appearance anxiety in patients with breast cancer in the period after mastectomy. Therefore, this study investigated the social appearance anxiety and social support status in women with breast cancer in our country. Materials and Methods: A descriptive cross-sectional study was conducted in breast cancer patients undergoing treatment or follow-up in Medical Oncology and General Surgery departments. Results: The mean age of the participants was$51.13{\pm}8.48$ years (range, 24-74 years) with nearly half of the patients (40.6%) aged 40-50 years. Of the patients, 39.1% had stage 3 breast cancer. The mean score on Cancer Patient's Social Support Scale (CPSSS) was$134.85{\pm}9.35$ , and there was a significant difference in CPSSS total scores betweena the age groups, educational levels, self-reported income levels and stage of disease (p<0.05). The mean Social Image Anxiety Scale (SIAS) score was found to be$34.30{\pm}9.35$ (min:16, max:66) in women participating in this study. The CPSSS and SIAS scores of the participants were inversely correlated, and the SIAS score was found to decrease with the increasing CPSSS score but with no statistically significant difference (r=-0.110, p=0.217). Conclusions: Social appearance anxiety is higher in the patients with poor social support. -
Bao, Ci-Hang;Liu, Kun;Wang, Xin-Tong;Ma, Wei;Wang, Jian-Bo;Wang, Cong;Jia, Yi-Bin;Wang, Na-Na;Tan, Bing-Xu;Song, Qing-Xu;Cheng, Yu-Feng 1803
Hepatoma-derived growth factor (HDGF) is a novel jack-of-all-trades in cancer. Here we quantify the prognostic impact of this biomarker and assess how consistent is its expression in solid tumors. A comprehensive search strategy was used to search relevant literature updated on October 3, 2014 in PubMed, EMBASE and WEB of Science. Correlations between HDGF expression and clinicopathological features or cancer prognosis was analyzed. All pooled HRs or ORs were derived from random-effects models. Twenty-six studies, primarily in Eastern Asia, covering 2,803 patients were included in the analysis, all of them published during the past decade. We found that HDGF overexpression was significantly associated with overall survival (OS) ($HR_{OS}=2.35$ , 95%CI=2.04-2.71, p<0.001) and disease free survival (DFS) ($HR_{DFS}=2.25$ , 95%CI =1.81-2.79, p<0.001) in solid tumors, especially in non-small cell lung cancer, hepatocellular carcinoma and cholangiocarcinoma (CCA). Moreover, multivariate survival analysis showed that HDGF overexpression was an independent predictor of poor prognosis ($HR_{OS}=2.41$ , 95%CI: 2.02-2.81, p<0.001;$HR_{DFS}=2.39$ , 95%CI: 1.77-3.24, p<0.001). In addition, HDGF overexpression was significantly associated with tumor category (T3-4 versus T1-2, OR=2.12, 95%CI: 1.17-3.83, p=0.013) and lymph node status (N+ versus N-, OR=2.37, 95%CI: 1.31-4.29, p=0.03) in CCA. This study provides a comprehensive examination of the literature available on the association of HDGF overexpression with OS, DFS and some clinicopathological features in solid tumors. Meta-analysis results provide evidence that HDGF may be a new indicator of poor cancer prognosis. Considering the limitations of the eligible studies, other large-scale prospective trials must be conducted to clarify the prognostic value of HDGF in predicting cancer survival. -
Gazel, Eymen;Tastemur, Sedat;Acikgoz, Onur;Yigman, Metin;Olcucuoglu, Erkan;Camtosun, Ahmet;Ceylan, Cavit;Ates, Can 1813
Background: The aim of this study was to research the importance of the neutrophil to lymphocyte ratio (NLR) in prediction of PSA recurrence after radical prostatectomy, which has not been reported so far. Materials and Methods: The data of 175 patients who were diagnosed with localised prostate cancer and underwent retropubic radical prostatectomy was retrospectively examined. Patient pre-operative hemogram parameters of neutrophil count, lymphocyte count and NLR were assessed. The patients whose PSAs were too low to measure after radical prostatectomy in their follow-ups, and then had PSAs of 0,2 ng/mL were considered as patients with PSA recurrence. Patients with recurrence made up Group A and patients without recurrence made up Group B. Results: In terms of the power of NLR value in distinguishing recurrence, the area under OCC was statistically significant (p<0.001) .The value of 2.494 for NLR was found to be a cut-off value which can be used in order to distinguish recurrence according to Youden index. According to this, patients with a higher NLR value than 2.494 had higher rates of PSA recurrence with 89.7% sensitivity and 92.6% specificity. Conclusions: There are certain parameters used in order to predict recurrence with today's literature data.We think that because NLR is easy to use in clinics and inexpensive, and also has high sensitivity and specificity values, it has the potential to be one of the parameters used in order to predict biochemical recurrence in future. -
Karaman, Erbil;Karaman, Yasemin;Numanoglu, Ceyhun;Ark, Hasan Cemal 1817
Background: Hemoglobin A1c(HgA1c) is a marker of poor gylcemic control and elevation HgA1c is associated with increased risk of many cancers. We aimed to determine the HgA1c levels in endometrial cancer cases and any relationship with stage and grade of disease. Materials and Methods: A retrospective data review was performed between June 2011 and October 2012 at a tertiary referral center in Turkey. The study included 35 surgically staged endometrial cancer patients and 40 healthy controls. Preoperative HgA1c levels drawn within 3 months before surgery were compared. Also the relationships between HgA1c levels and stage, grade and hystologic type of cancer cases were evaluated. Results: The mean HgA1c levels were statistically significantly higher at$6.19{\pm}1.44$ in endometrial cancer cases than the$5.61{\pm}0.58$ in controls (p=0.027). With endometrial cancer cases, the mean HgA1c level was found to be$6.62{\pm}1. 40$ for stage I and$6.88{\pm}1.15$ for stages II-IV (p=0.07). The figures were$6.74{\pm}1.65$ for endometrioid and$6.63{\pm}1.41$ for non-endometrioid type tumors (p=0.56). Mean HgA1c levels of$6.72{\pm}1.14$ for grade 1 and$6.62{\pm}1.42$ for grade 2-3 were observed (p=0.57). Conclusions: HgA1c levels in endometrial cancer patients were statistically higher than healthy controls. However, HgA1c did not show any significant correlation with stage, grade and histologic type in endometrial cancer cases. -
Zhao, Hong;Zou, Li-Wei;Zheng, Sui-Sheng;Geng, Xiao-Ping 1821
Background: Associations between the NQO1 C609T polymorphism and hepatocellular carcinoma (HCC) risk are a subject of debate. We therefore performed the present meta-analysis to evaluate links with HCC susceptibility. Materials and Methods: Several major databases (PubMed, EBSCO), the Chinese national knowledge infrastructure (CNKI) and the Wanfang database were searched for eligible studies. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to measure the strength of associations. Results: A total of 4 studies including 1,325 patients and 1,367 controls were identified. There was a significant association between NQO1 C609T polymorphism and HCC for all genetic models (allelic model: OR=1.45, 95%CI=1.23-1.72, p<0.01; additive model: OR=1.96, 95%CI=1.57-2.43, p<0.01; dominant model: OR=1.62, 95%CI=1.38-1.91, p<0.01; and recessive model: OR=1.53, 95%CI=1.26-1.84, p<0.01). On subgroup analysis, similarly results were identified in Asians. For Asians, the combined ORs and 95% CIs were (allelic model: OR=1.50, 95%CI=1.24-1.82, p<0.01; additive model: OR=2.11, 95%CI=1.48-3.01, p<0.01; dominant model: OR=1.69, 95%CI=1.42-2.02, p<0.01; and recessive model: OR=1.59, 95%CI=1.16-2.19, p<0.01). Conclusions: The current meta-analysis suggested that the NQO1 C609T polymorphism could be a risk factor for developing HCC, particularly in the Chinese population. -
Koike, Hiroyuki;Nozawa, Masahiro;De Velasco, Marco A;Kura, Yurie;Ando, Naomi;Fukushima, Emiko;Yamamoto, Yutaka;Hatanaka, Yuji;Yoshikawa, Kazuhiro;Nishio, Kazuto;Uemura, Hirotsugu 1827
Background: We generated a mouse model of prostate cancer based on the adult-prostate-specific inactivation of phosphatase and tensin homolog (PTEN) using the Cre-loxP system. The potential of our mice as a useful animal model was examined by evaluating the chemopreventive efficacy of the anti-androgen, chlormadinone acetate (CMA). Materials and Methods: Six-week-old mice were treated subcutaneously with$50{\mu}g/g$ of CMA three times a week for 9 or 14 weeks and sacrificed at weeks 15 and 20. Macroscopic change of the entire genitourinary tract (GUT) and histologically evident prostate gland tumor development were evaluated. Proliferation and apoptosis status in the prostate were examined by immunohistochemistry. Results: CMA triggered significant shrinkage of not only the GUT but also prostate glands at 15 weeks compared to the control (p=0.017 and p=0.010, respectively), and the trend became more marked after a further five-weeks of treatment. The onset of prostate adenocarcinoma was not prevented but the proliferation of cancer cells was inhibited by CMA, which suggested the androgen axis is critical for cancer growth in these mice. Conclusions: Conditional PTEN-deficient mice are useful as a preclinical model for chemoprevention studies and serve as a valuable tool for the future screening of potential chemopreventive agents. -
Banjerdpongchai, Ratana;Wudtiwai, Benjawan;Pompimon, Wilart 1833
An aristolactam-type alkaloid, isolated from Orophea enterocarpa, is enterocarpam-III (10-amino-2,3,4,6-tetramethoxyphenanthrene-1-carboxylic acid lactam). It is cytotoxic to various human and murine cancer cell lines; however, the molecular mechanisms remain unclear. The aims of this study were to investigate cytotoxic effects on and mechanism (s) of human cancer cell death in human hepatocellular carcinoma HepG2 and human invasive breast cancer MDA-MB-231 cells compared to normal murine fibroblast NIH3T3 cells. Cell viability was determined by MTT assay to determine$IC_{10}$ ,$IC_{20}$ and$IC_{50}$ levels, reactive oxygen species (ROS) production with 2',7'-dichlorohydrofluorescein diacetate and the caspase-3, -8 and -9 activities using specific chromogenic (p-nitroaniline) tetrapeptide substrates, viz., DEVD-NA, IETD-NA and LEHD-NA and employing a microplate reader. Mitochondrial transmembrane potential (MTP) was measured by staining with 3, 3'-dihexyloxacarbocyanine iodide ($DiOC_6$ ) and using flow cytometry. The compound was cytotoxic to HepG2 and MDA-MB-231 cells with the$IC_{50}$ levels of$26.0{\pm}4.45$ and$51.3{\pm}2.05{\mu}M$ , respectively. For murine normal fibroblast NIH3T3 cells, the$IC_{50}$ concentration was$81.3{\pm}10.1{\mu}M$ . ROS production was reduced in a dose-response manner in HepG2 cells. The caspase-9 and -3 activities increased in a concentration-dependent manner, whereas caspase-8 activity did not alter, indicating the intrinsic pathway activation. Enterocarpam-III decreased the mitochondrial transmembrane potential (MTP) dose-dependently in HepG2 cells, suggesting that the compound induced HepG2 cell apoptosis via the mitochondrial pathway. In conclusion, enterocarpam-III inhibited HepG2 and MDA-MB-231 cell proliferation and induced human HepG2 cells to undergo apoptosis via the intrinsic (mitochondrial) pathway and induction of caspase-9 activity. -
Background: MicroRNAs are a class of noncoding RNAs which regulate multiple cellular processes during tumor development. The purpose of this report is to investigate the clinicopathological and prognostic significance of miR-218 in human gliomas. Materials and Methods: Quantitative RT-PCR (qRT-PCR) was conducted to detect the expression of miR-218 in primary normal human astrocytes, three glioma cell lines and 98 paired glioma and adjacent normal brain tissues.Associations of miR-218 with clinicopathological variables of glioma patients were statistically analyzed. Finally, a survival analysis was performed using the Kaplan-Meier method and Cox's proportional hazards model. Results: The expression level of miR-218 in primary normal human astrocytes was significantly higher than that in glioma cell lines (p<0.01). Also, the expression level of miR-218 in glioma tissues was significantly downregulated in comparison with that in the adjacent normal brain tissues (p<0.001). Statistical analyses demonstrated that low miR-218 expression was closely associated with advanced WHO grade (p=0.002) and low Karnofsky performance score (p=0.010) of glioma patients. Kaplan-Meier analysis with the log-rank test showed that patients with low-miR-218 expression had poorer disease-free survival and overall survival (p=0.0045 and 0.0124, respectively). Multivariate analysis revealed that miR-218 expression was independently associated with the disease-free survival (p=0.009) and overall survival (p=0.004) of glioma patients. Conclusions: Our results indicate that miR-218 is downregulated in gliomas and that its status might be a potential valuable biomarker for glioma patients.
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Khorasani, Soheila;Rezaei, Satar;Rashidian, Hamideh;Daroudi, Rajabali 1845
Background: Cancer is recently one of the major concerns of the public health both in the world and Iran. To inform priorities for cancer control, this study estimated years of potential life lost (YPLL) and productivity losses due to cancer-related premature mortality in Iran in 2012. Materials and Methods: The number of cancer deaths by sex for all cancers and the ten leading causes of cancer deaths in Iran in 2012 were obtained from the GLOBOCAN database. The life expectancy method and the human capital approach were used to estimate the YPLL and the value of productivity lost due to cancer-related premature mortality. Results: There were 53,350 cancer-related deaths in Iran. We estimated that these cancer deaths resulted in 1,112,680 YPLL in total, 563,332 (50.6%) in males and 549,348 (49.4%) in females. The top 10 ranked cancers accounted for 75% of total death and 70% of total YPLL in the males and 69% for both death and YPLL in the females. The largest contributors for YPLL in the two genders were stomach and breast cancers, respectively. The total cost of lost productivity due to cancer-related premature mortality discounted at 3% rate in Iran, was US$ 1.93 billion. The most costly cancer for the males was stomach, while for the females it was breast cancer. The percentage of the total costs that were attributable to the top 10 cancers was 67% in the males and 71% in the females. Conclusions: The YPLL and productivity losses due to cancer-related premature mortality are substantial in Iran. Setting resource allocation priorities to cancers that occur in younger working-age individuals (such as brain and central nervous system) and/or cancers with high incidence and mortality rates (such as stomach and breast) could potentially decrease the productivity losses and the YPLL to a great extent in Iran. -
Tanoglu, Alpaslan;Balta, Ahmet Ziya;Berber, Ufuk;Ozdemir, Yavuz;Emirzeoglu, Levent;Sayilir, Abdurrahim;Sucullu, Ilker 1851
Background: There are increasing data about microRNAs (miRNA) in the literature, providing abundant evidence that they play important roles in pathogenesis and development of colorectal cancer. In this study, we aimed to investigate the miRNA expression profiles in surgically resected specimens of patients with recurrent and non-recurrent colorectal cancer. Materials and Methods: The study population included 40 patients with stage II colorectal cancer (20 patients with recurrent tumors, and 20 sex and age matched patients without recurrence), who underwent curative colectomy between 2004 and 2011 without adjuvant therapy. Expression of 16 miRNAs (miRNA-9, 21, 30d, 31, 106a, 127, 133a, 133b, 135b, 143, 145, 155, 182, 200a, 200c, 362) was verified by quantitative real-time polymerase chain reaction (qRT-PCR) in all resected colon cancer tissue samples and in corresponding normal colonic tissues. Data analyses were carried out using SPSS 15 software. Values were statistically significantly changed in 40 cancer tissues when compared to the corresponding 40 normal colonic tissues (p<0.001). MiR-30d, miR-133a, miR-143, miR-145 and miR-362 expression was statistically significantly downregulated in 40 resected colorectal cancer tissue samples (p<0.001). When we compared subgroups, miRNA expression profiles of 20 recurrent cancer tissues were similar to all 40 cancer tissues. However in 20 non-recurrent cancer tissues, miR-133a expression was not significantly downregulated, moreover miR-133b expression was significantly upregulated (p<0.05). Conclusions: Our study revealed dysregulation of expression of ten miRNAs in Turkish colon cancer patients. These miRNAs may be used as potential biomarkers for early detection, screening and surveillance of colorectal cancer, with functional effects on tumor cell behavior. -
Chen, Nan;Wang, Jia-Rong;Huang, Lin;Yang, Yang;Jiang, Ya-Mei;Guo, Xiao-Jiang;He, Ya-Zhou;Zhou, Yan-Hong 1857
Background: Alpha-methylacyl-CoA racemase(AMACR) is thought to play key roles in diagnosis and prognosis of prostate cancer. However, studies of associations between AMACR gene polymorphisms and prostate cancer risk reported inconsistent results. Therefore, we conducted the present meta-analysis to clarify the link between AMACR gene polymorphisms and prostate cancer risk. Materials and Methods: A literature search was performed in PubMed, Embase, China National Knowledge Infrastructure (CNKI), Wanfang and Weipu databases. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated to assess the strength of any association between AMACR polymorphisms and prostate cancer risk. Subgroup analyses by ethnicity, source of controls, quality control and sample size were also conducted. Results: Five studies covering 3,313 cases and 3,676 controls on five polymorphisms (D175G, M9V, S201L, K277E and Q239H) were included in this meta-analysis. Significant associations were detected between prostate cancer and D175G (dominant model: OR=0.89, 95%CI=0.80-0.99, P=0.04) and M9V (dominant model: OR=0.87, 95%CI=0.78-0.97, P=0.01) polymorphisms as well as that in subgroup analyses. We also observed significant decreased prostate cancer risk in the dominant model (OR=0.90, 95%CI=0.81-0.99, P=0.04) for the S201L polymorphism. However, K277E and Q239H polymorphisms did not appear to be related to prostate cancer risk. Conclusions: The current meta-analysis indicated that D175G and M9V polymorphisms of the AMACR gene are related to prostate cancer. The S201L polymorphism might also be linked with prostate cancer risk to some extent. However, no association was observed between K277E or Q239H polymorphisms and susceptibility to prostate cancer. -
While health information-seeking behavior as an indicator of health communication of patients including cancer survivors has been researched, few studies have focused on how socioeconomic position and media use combine to influence health-related information seekers. This study examined social characteristics of health information-seeking behavior taking into account an individual's socioeconomic position and their media use in Korea, a developed country. The data for this study came from a survey of 1,010 respondents drawn from a nationally representative sample in the Republic of Korea. We conducted multivariate logistic regression analyses for gender-specific effects. We found that men who reported high household income were one and half times more likely to seek health information than those with low income status. We also found that women who performed Internet searches by computer at home were almost two times more likely to seek health information than those who did not. Similar results were found for men as well. Our analyses revealed that socioeconomic position and media use are associated with health information-seeking behavior by gender. Studies on information seekers may bring us more effective health promotion and relevant intervention for people with chronic conditions including cancer survivors.
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Fateh, Abolfazl;Aghasadeghi, Mohammad Reza;Keyvani, Hossein;Mollaie, Hamid Reza;Yari, Shamsi;Tasbiti, Ali Reza Hadizade;Ghazanfari, Morteza;Monavari, Seyed Hamid Reza 1873
Background: A recent genome-wide association study (GWAS) on patients with chronic hepatitis C (CHC) treated with peginterferon and ribavirin (pegIFN-${\alpha}$ /RBV) identified a single nucleotide polymorphism (SNP) on chromosome 19 (rs12979860) which was strongly associated with a sustained virological response (SVR). The aim of this study was twofold: to study the relationship between IL28B rs12979860 and sustained virological response (SVR) to pegIFN-${\alpha}$ /RVB therapy among CHC patients and to detect the rs12979860 polymorphism by high resolution melting curve (HRM) assay as a simple, fast, sensitive, and inexpensive method. Materials and Methods: The study examined outcomes in 100 patients with chronic hepatitis C in 2 provinces of Iran from December 2011 to June 2013. Two methods were applied to detect IL28B polymorphisms: PCR-sequencing as a gold standard method and HRM as a simple, fast, sensitive, and inexpensive method. Results: The frequencies of IL28B rs12979860 CC, CT, and TT alleles in chronic hepatitis C genotype 1a patients were 10% (10/100), 35% (35/100), and 6% (6/100) and in genotype 3a were 13% (13/100), 31% (31/100), and 5% (5/100), respectively. In genotype 3a infected patients, rs12979860 (CC and CT alleles) and in genotype 1a infected patients (CC allele) were significantly associated with a sustained virological response (SVR). The SVR rates for CC, CT and TT (IL28B rs12979860) were 18%, 34% and 4%, respectively. Multiple logistic regression analysis identified two independent factors that were significantly associated with SVR: IL-28B genotype (rs 12979860 CC vs TT and CT; odds ratio [ORs], 7.86 and 4.084, respectively), and HCV subtype 1a (OR, 7.46). In the present study, an association between SVR rates and IL28B polymorphisms was observed. Conclusions: The HRM assay described herein is rapid, inexpensive, sensitive and accurate for detecting rs12979860 alleles in CHC patients. This method can be readily adopted by any molecular diagnostic laboratory with HRM capability and will be clinically beneficial in predicting treatment response in HCV genotype 1 and 3 infected patients. In addition, it was demonstrated that CC and CT alleles in HCV-3a and the CC allele in HCV-1a were significantly associated with response to pegIFN-${\alpha}$ /RBV treatment. The present results may help identify subjects for whom the therapy might be successful. -
Zheng, Chun-Long;Qiu, Chen;Shen, Mei-Xiao;Qu, Xiao;Zhang, Tie-Hong;Zhang, Ji-Hong;Du, Jia-Jun 1881
Background: The vascular endothelial growth factor family has been implicated in tumorigenesis and metastasis. The prognostic value of each vascular endothelial growth factor family member, particular VEGF/VEGFR co-expression, in patients with non-small lung cancer remains controversial. Materials and Methods: Relevant literature was identified by searching PubMed, EMBASE and Web of Science. Studies evaluating expression of VEGFs and/or VEGFRs by immunohistochemistry or ELISA in lung cancer tissue were eligible for inclusion. Hazard ratios (HRs) and 95% confidence intervals (CIs) from individual study were pooled by using a fixed- or random-effect model, heterogeneity and publication bias analyses were also performed. Results: 74 studies covering 7,631 patients were included in the meta-analysis. Regarding pro-angiogenesis factors, the expression of VEGFA (HR=1.633, 95%CI: 1.490-1.791) and VEGFR1 (HR=1.924, 95%CI: 1.220-3.034) was associated separately with poor survival. Especially, VEGFA over-expression was an independent prognostic factor in adenocarcinoma (ADC) (HR=1.775, 95%CI: 1.384-2.275) and SCC (HR=2.919, 95%CI: 2.060-4.137). Co-expression of VEGFA/VEGFR2 (HR=2.011, 95%CI: 1.405-2.876) was also significantly associated with worse survival. For lymphangiogenesis factors, the expression of VEGFC (HR=1.611, 95%CI: 1.407-1.844) predicted a poor prognosis. Co-expression of VEGFC/VEGFR3 (HR=2.436, 95%CI: 1.468-4.043) emerged as a preferable prognostic marker. Conclusions: The expression of VEGFA (particularly in SCC and early stage NSCLC), VEGFC, VEGFR1 indicates separately an unfavorable prognosis in patients with NSCLC. Co-expression VEGFA/VEGFR2 is comparable with VEGFC/VEGFR3, both featuring sufficient discrimination value as preferable as prognostic biologic markers. -
Ozdemir, Sevim;Akin, Mustafa;Coban, Yasin;Yildirim, Cumhur;Uzel, Omer 1897
Purpose: To evaluate acute toxicity in nasopharyngeal cancer (NPC) patients treated with intensity modulated radiotherapy (IMRT)/volumetric modulated arc therapy (VMAT) with or without cisplatin-based chemotherapy. Materials and Methods: A total of 45 newly diagnosed, histologically proven non-metastatic NPC patients treated with IMRT between May 2010 and December 2012, were evaluated retrospectively, 37 planned with Eclipse and 8 with Prowess Panther treatment planning system. The doses to the planning target volumes of primary tumor and involved lymph nodes, high risk region, and uninvolved regional nodal areas were 70 Gy, 60 Gy, and 54 Gy respectively and delivered simultaneously over 33 fractions to 39 patients. Another 6 patients irradiated with sequential boost technique. Some 84.4% of patients received chemotherapy. Acute toxicities were graded according to the Radiation Therapy Oncology Group scoring criteria and Common Terminology Criteria for Adverse Events (CTCAE) for chemotherapy side effects. Results: Median age was 43 years (14-79) and all patients were WHO type II. Grade 1 mucositis and dysphagia were observed in 17 (37.8%), and 10 (22.2%) patients, respectively. The incidence of acute grade 2 mucositis and dysphagia was 55.6% and 68.9%, respectively. The most common chemoradiotherapy related acute toxicities were nausea, leucopenia and thrombocytopenia. Grade 3 toxicity was detected in 13 (28.8%) cases. No grade 4 toxicity was occurred. Mean weight loss was 9%. None of the patients required the insertion of percutaneous endoscopic gastrostomy for nutritional support. Radiation therapy was completed without interruption in all patients. Conclusions: IMRT is a safe and effective treatment modality, and well tolerated by patients in the treatment of nasopharyngeal carcinoma. No unexpected side effects were observed. -
Tang, Weng Heng;Alip, Adlinda;Saad, Marniza;Phua, Vincent Chee Ee;Chandran, Hari;Tan, Yi Hang;Tan, Yan Yin;Kua, Voon Fong;Wahid, Mohamed Ibrahim;Tho, Lye Mun 1901
Background: Brain metastases occur in about 20-40% of patients with non-small-cell lung carcinoma (NSCLC), and are usually associated with a poor outcome. Whole brain radiotherapy (WBRT) is widely used but increasingly, more aggressive local treatments such as surgery or stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT) are being employed. In our study we aimed to describe the various factors affecting outcomes in NSCLC patients receiving local therapy for brain metastases. Materials and Methods: The case records of 125 patients with NSCLC and brain metastases consecutively treated with radiotherapy at two tertiary centres from January 2006 to June 2012 were analysed for patient, tumour and treatment-related prognostic factors. Patients receiving SRS/SRT were treated using Cyberknife. Variables were examined in univariate and multivariate testing. Results: Overall median survival was 3.4 months (95%CI: 1.7-5.1). Median survival for patients with multiple metastases receiving WBRT was 1.5 months, 1-3 metastases receiving WBRT was 3.6 months and 1-3 metastases receiving surgery or SRS/SRT was 8.9 months. ECOG score (${\leq}2$ vs >2, p=0.001), presence of seizure (yes versus no, p=0.031), treatment modality according to number of brain metastases (1-3 metastases+surgery or$SRS/SRT{\pm}WBRT$ vs 1-3 metastases+WBRT only vs multiple metastases+WBRT only, p=0.007) and the use of post-therapy systemic treatment (yes versus no, p=0.001) emerged as significant on univariate analysis. All four factors remained statistically significant on multivariate analysis. Conclusions: ECOG${\leq}2$ , presence of seizures, oligometastatic disease treated with aggressive local therapy (surgery or SRS/SRT) and the use of post-therapy systemic treatment are favourable prognostic factors in NSCLC patients with brain metastases. -
Zong, Li-Ju;Zhang, You-Zhong;Yang, Xing-sheng;Jiang, Jie;Cui, Bao-Xia;Qiao, Yun-Bo;Li, Li;Jiang, Kan;Zhang, Wen-Jing;Kong, Bei-Hua;Shen, Keng 1907
Purpose: The study was designed to: (1) investigate the prevalence of high-risk human papillomavirus (HR-HPV) infection and cervical neoplasia; and (2) evaluate clinical performance of visual inspection with acetic acid/ Lugol's iodine (VIA /VILI), Pap smear, high-risk human papillomavirus (HR-HPV) DNA test for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and (3) explore appropriate screening approach in rural areas of Shandong Province. Materials and Methods: A total of 3,763 eligible women from Yiyuan County in Yimeng mountainous areas of rural Shandong, China, were enrolled and underwent Pap smear, HR-HPV DNA testing by Hybrid Capture 2 (HC2), and VIA /VILI tests. Women positive in any test were referred to colposcopy and biopsy as indicated. Results: The prevalence of HR-HPV infection among all enrolled women was 11.1% and that in healthy women was 9.9%. In total 33 cases of CIN1, 16 cases of CIN2, 6 cases of CIN3 but none of cervical cancer were detected and the crude prevalence of CIN2+ was 0.58%. For detecting CIN2+, the sensitivity of HR-HPV DNA testing, VIA/VILI, Pap smear was 90.9%, 77.3%, 81.8%, respectively. Pap smear had the best specificity of 98.2%, followed by HR-HPV DNA testing with specificity of 89.4%, VIA/VILI had the lowest specificity of 81.2%. Colposcopy referral rate of HR-HPV DNA testing, VIA/VILI, Pap smear was 11.1%, 18.5%, 2.3%, respectively. Conclusions: Our results suggest that HR-HPV DNA testing alone might be appropriate for primary cervical cancer screening in rural low-resource areas of Shandong Province, China. -
Koca, Timur;Arslan, Deniz;Basaran, Hamit;Cerkesli, Arda Kaymak;Tastekin, Didem;Sezen, Duygu;Koca, Ozlem;Binici, Dogan Nasir;Bassorgun, Cumhur Ibrahim;Ozdogan, Mustafa 1913
Background: Oesophageal squamous cell carcinoma (ESCC) is endemic in the Eastern Anatolian region of Turkey. The present study was performed to identify risk factors for ESCC that specifically reflect the demography and nutritional habits of individuals living in this region. Materials and Methods: The following parameters were compared in 208 ESCC patients and 200 control individuals in the Eastern Anatolian region: age, sex, place of living, socioeconomic level, education level, smoking, alcohol intake, nutritional habits, and food preservation methods. Results: The mean age of ESCC patients was 56.2 years, and 87 (41.8%) were 65 years-old or older. The ratio of women to men in the patient group was 1.39/1. ESCC patients consumed significantly less fruit and yellow or green vegetables and more hot black tea, 'boiled yellow butter', and mouldy cheese than did control individuals. Residence in rural areas, smoking, and cooking food by burning animal manure were also significantly associated with ESCC. Conclusions: The consumption of boiled yellow butter and mouldy cheese, which are specific to the Eastern Anatolian region, and the use of animal manure for food preparation were identified as risk factors in this region. Further studies are required to potentially identify the carcinogenic substances that promote the development of ESCC in this region. -
Iranmanesh, Zahra;Mollaie, Hamid Reza;Arabzadeh, Seyed Alimohammad;Zahedi, Mohammad Javad;Fazlalipour, Mehdi;Ebrahimi, Saeede 1919
Polymorphisms in the region of the interleukin IL-28 gene on chromosome 19 have been related with clearance of hepatitis C virus (HCV), a major human pathogen responsible for chronic hepatitis, cirrhosis and hepatocellular carcinoma. About 3% of the world's population is infected with HCV. The long-term response to therapy is influenced by many host and viral factors, and recent evidence has indicated that some host genetic polymorphisms related to IL-28 are the most powerful predictors of virological response in patients with HCV. This study assessed frequency of the IL-28 polymorphism (rs8099917) in 50 patients (39 men and 11 women) with chronic hepatitis C using ZNA probe real time PCR new method. All patients were tested for genotype of HCV and the HCV viral load. In parallel, the levels of SGOT, SGPT and ALK enzymes were assessed. Treatment using Peg-interferon alpha with ribavirin was conducted for patients and subsequently samples were collected to detect any change in viral load or liver enzyme rates. The overall frequency of the TT allele is 74%, TG allele 20% and GG allele 6% and the percent of patients who had T allele was 84%. Clear reduction in viral load and liver enzymes was reported in patients with the T allele. Especially for genotype 1 which is relatively resistant to treatment, these alleles may have a role in this decline. In conclusion, we showed that IL-28 polymorphism rs8099917 strongly predicts virological response in HCV infection and that real-time PCR with Zip nucleic acid probes is a sensitive, specific and rapid detection method for detection of SNPs which will be essential for monitoring patients undergoing antiviral therapy. -
Liu, Li-Heng;Liu, Ming;Wei, Ran;Jin, Er-Hu;Liu, Yu-Hui;Xu, Liang;Li, Wen-Wu;Huang, Yong 1925
Background: To investigate whether CT findings can predict the invasiveness of persistent cancerous pure ground glass opacity (pGGO) by correlating the CT imaging features of persistent pGGO with pathological changes. Materials and Methods: Ninety five patients with persistent pGGOs were included. Three radiologists evaluated the morphologic features of these pGGOs at high resolution CT (HRCT). Binary logistic regression was used to assess the association between CT findings and histopathological classification (pre-invasive and invasive groups). Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of diameters. Results: A total of 105 pGGOs were identified. Between pre-invasive (atypical adenomatous hyperplasia, AAH, and adenocarcinoma in situ, AIS) and invasive group (minimally invasive adenocarcinoma, MIA and invasive lung adenocarcinomas, ILA), there were significant differences in diameter, spiculation and vessel dilatation (p<0.05). No difference was found in air-bronchogram, bubble-lucency, lobulated-margin, pleural indentation or vascular convergence (p>0.05). The optimal threshold value of the diameters to predict the invasiveness of pGGO was 12.50mm. Conclusions: HRCT features can predict the invasiveness of persistent pGGO. The pGGO with a diameter more than 12.50mm, presences of spiculation and vessel dilatation are important factors to differentiate invasive adenocarcinoma from pre-invasive cancerous lesions. -
Murray, Nigel P;Miranda, Roxana;Ruiz, Amparo;Droguett, Elsa 1929
Purpose: To determine the diagnostic yield of primary circulating tumor cells in women with suspicion of breast cancer, detected as a result of an abnormal mammography. Materials and Methods: Consecutive women presenting for breast biopsy as a result of a mammogram BiRADs of 3 or more, had an 8ml blood sample taken for primary circulating tumor cell (CTC) detection. Mononuclear cells were obtained using differential gel centrifugation and CTCs identified using standard immunocytochemistry using anti-mammoglobin. A test was determined to be positive if 1 CTC was detected. Results: A total of 144 women with a mean age of$54.7{\pm}15.6$ years participated, 78/144 (53.0%) had breast cancer on biopsy, 65/140 (46.3%) benign pathologies and 1(0.7%) non-Hogkins lymphoma. Increasing BiRADs scores were associated with increased cancer detection (p=0.004, RR 1.00, 4.24, 8.50). CTC mammoglobin positive had a sensitivity of 81.1% and specificity of 90.9%, with positive and negative predictive values of 90.9% and 81.1% respectively. Mammoglobin positive CTCs detected 87% of invasive cancers, while poorly differentiated cancers were negative for mammoglobin. Only 50% of in situ cancers and none of the intraductal cancers had CTCs detected. Menopausal status did not affect the diagnostic yield of the CTC test, which was higher in women with BiRADS 4 mammograms. There was a significant trend (p<0.0001 Chi squared for trends) in CTC detection frequency from intraductal, in situ and invasive (OR 1.00, 8.00, 472.00). Conclusions: The use of primary CTC detection in women suspected of breast cancer has potential uses, especially with invasive cancer, but it failed to detect intra-ductal cancer and 50% of in situ cancer. There was no difference in the diagnostic yield between pre and post menopausal women. To confirm its use in reducing biopsies in women with BIRADs 4a mammagrams and in the detection of interval invasive breast cancer, larger studies are needed. -
Lack of Participation of the GSTM1 Polymorphism in Cervical Cancer Development in Northeast ThailandNatphopsuk, Sitakan;Settheetham-Ishida, Wannapa;Settheetham, Dariwan;Ishida, Takafumi 1935
The potential association between the GSTM1 deletion polymorphism and risk of cervical cancer was investigated in Northeastern Thailand. DNA was extracted from buffy coat specimens of 198 patients with squamous cell carcinoma of the cervix and 198 age-matched healthy controls. Genotyping of the GSTM1 was conducted by using two PCR methods, a short- and a long-PCR. Distribution of the GSTM1 genotypes in between the cases and the controls was not significantly different (p>0.5 by${\chi}^2$ test). The results suggest that the GSTM1 deletion polymorphism is not a risk factor for squamous cell carcinoma of the cervix in the northeast Thai women. -
Ma, Ji-Yong;Yan, Hai-Jun;Yang, Zhen-Hua;Gu, Wei 1939
MicroRNA-27a (miR-27a) is deemed to be an oncogene that plays an important role in development of various cancers, and single nucleotide polymorphism (SNP) of miR-27a can influence the maturation or aberrant expression of hsa-miR27a, resulting in increased risk of cancer and poor prognosis for non-small cell lung cancer (NSCLC). This study aimed to assess the effects of rs895819 within miR-27a on susceptibility and prognosis of NSCLC patients in 560 clinical confirmed cases and 568 healthy check-up individuals. Adjusted odds/hazard ratios (ORs/HRs) and 95% confidential intervals (CIs) were calculated to evaluate the association between rs895819 and the risk and prognosis of NSCLC. The results showed that allele A and genotype GG of rs895819 were significantly associated with an increased risk of NSCLC (38.9% vs 30.8%, adjusted OR=1.26, 95%CI=1.23-1.29 for allele G vs A; 18.1% vs 11.7%, adjusted OR=1.67, 95%CI=1.59-1.75 for genotype GG vs AA). Moreover, positive associations were also observed in dominant and recessive models (53.7% vs 49.9%, adjusted OR=1.17, 95%CI=1.13-1.20 for GG/AG vs AA; 18.1% vs 11.7%, adjusted=1.65, 95%CI=1.58-1.73). However, no significant association was found between rs895819 and the prognosis of NSCLC in genotype, dominant and recessive models. These results suggested that miR-27a might be involved in NSCLC carcinogenesis, but not in progression of NSCLC. The allele G, genotype GG and allele G carrier (GG/AG vs AA) of rs895819 might be genetic susceptible factors for NSCLC. Further multi-central, large sample size and well-designed prospective studies as well as functional studies are warranted to verify our findings. -
Mokarram, Pooneh;Kavousipour, Soudabeh;Sarabi, Mostafa Moradi;Mehrabani, Golnosh;Fahmidehkar, Mohammad Ali;Shamsdin, Seyedeh Azra;Alipour, Abbas;Naini, Mahvash Alizade 1945
Inflammatory bowel disease (IBD) is a disease strongly associated with colorectal cancer (CRC) as a well-known precancerous condition. Alterations in DNA methylation and mutation in K-ras are believed to play an early etiopathogenic role in CRC and may also an initiating event through deregulation of molecular signaling. Epigenetic silencing of APC and SFRP2 in the WNT signaling pathway may also be involved in IBD-CRC. The role of aberrant DNA methylation in precancerous state of colorectal cancer (CRC) is under intensive investigation worldwide. The aim of this study was to investigate the status of promoter methylation of MGMT-B, APC1A and SFRP2 genes, in inflamed and normal colon tissues of patients with IBD compared with control normal tissues. A total of 52 IBD tissues as well as corresponding normal tissues and 30 samples from healthy participants were obtained. We determined promoter methylation status of MGMT-B, SFRP2 and APC1A genes by chemical treatment with sodium bisulfite and subsequent MSP. The most frequently methylated locus was MGMT-B (71%; 34 of 48), followed by SFRP2 (66.6 %; 32 of 48), and APC1A (43.7%; 21 of 48). Our study demonstrated for the first time that hypermethylation of the MGMT-B and the SFRP2 gene promoter regions might be involved in IBD development. Methylation of MGMT-B and SFRP2 in IBD patients may provide a method for early detection of IBD-associated neoplasia. -
Shridhar, Krithiga;Dey, Subhojit;Bhan, Chandra Mohan;Bumb, Dipika;Govil, Jyostna;Dhillon, Preet K 1953
Background: In India, cancer accounts for 7.3% of DALY's, 14.3% of mortality with an age-standardized incident rate of 92.4/100,000 in men and 97.4/100,000 in women and yet there are no nationwide screening programs. Materials and Methods: We calculated age-standardized and age-truncated (30-69 years) detection rates for men and women who attended the Indian Cancer Society detection centre, New Delhi from 2011-12. All participants were registered with socio-demographic, medical, family and risk factors history questionnaires, administered clinical examinations to screen for breast, oral, gynecological and other cancers through a comprehensive physical examination and complete blood count. Patients with an abnormal clinical exam or blood result were referred to collaborating institutes for further investigations and follow-up. Results: A total of n=3503 were screened during 2011-12 (47.8% men, 51.6% women and 0.6% children <15 years) with a mean age of 47.8 yrs (${\pm}15.1yrs$ ); 80.5% were aged 30-69 years and 77.1% had at least a secondary education. Tobacco use was reported by 15.8%, alcohol consumption by 11.9% and family history of cancer by 9.9% of participants. Follow-up of suspicious cases yielded 45 incident cancers (51.1% in men, 48.9% in women), consisting of 55.5% head and neck (72.0% oral), 28.9% breast, 6.7% gynecological and 8.9% other cancer sites. The age-standardized detection rate for all cancer sites was 340.8/100,000 men and 329.8/100,000 women. Conclusions: Cancer screening centres are an effective means of attracting high-risk persons in low-resource settings. Opportunistic screening is one feasible pathway to address the rising cancer burden in urban India through early detection. -
Fang, Jia-Ying;Wu, Ku-Sheng;Zeng, Yang;Tang, Wen-Rui;Du, Pei-Ling;Xu, Zhen-Xi;Xu, Xiao-Ling;Luo, Jia-Yi;Lin, Kun 1959
Purpose: To investigate the distribution of liver cancer mortality as well as its developing trend from 1991 to 2012, forecast the future five-year trend, and provide a basis for the comprehensive prevention and management. Materials and Methods: Mortality data for liver cancer in China from 1991 to 2012 were used to describe characteristics and distribution of liver cancer mortality. Trend surface analysis was used to study the geographical distribution of liver cancer mortality. Curve estimation, time series modeling, gray modeling (GM) and joinpoint regression were used to predict and forecast future trends. Results: The mortality rate of liver cancer has constantly increased in China since 1991. Rates in rural areas are higher than in urban areas, and in males are higher than in females. In addition, our data predicted that the trend will continue to increase in the next 5 years. The age-specific mortality of liver cancer increases with age and peaks in the group of 80-84 years old. Geographical analysis showed the liver mortality rate was higher in the southeast provinces, such as Jiangsu, Zhejiang and Guangdong, and southwest regions like Guangxi Province. Conclusions: The standardized mortality rate of liver cancer in China has consistently increased from 1991 to 2012, and the upward trend is predicted to continue in the future. Much better prevention and management of liver cancer is needed in high mortality areas (the southwestern and southeastern parts of China) and high mortality age groups (80- to 84-year-olds), especially in rural areas. -
Ulger, Sukran;Kizilarslanoglu, Muhammet Cemal;Kilic, Mustafa Kemal;Kilic, Diclehan;Cetin, Bekir Eren;Ulger, Zekeriya;Karahacioglu, Eray 1965
Cancer prevalance and incidence is increasing with aging of populations and age is a critical factor in decision-making for anti-cancer treatment. However it is believed that chronological age is not enough to guide management in elderly cancer patients. Multidisciplinary evaluation and comprehensive geriatric assessment has gained importance regarding the treatment selection especially for definitive anti-cancer therapy recently. We here aimed to analyse the effect of the comprehensive geriatric assessment parameters on radiotherapy toxicity and tolerability in a series of geriatric cancer patients in Turkey. -
Edesa, Wael Abdelgawad;Abdelmalek, Raafat Ragaey 1971
Background: To evaluate our results in terms of response, survival and toxicity profile of sunitinib among Egyptian patients with metastatic renal cell carcinoma. Materials and Methods: Between January 2010 and December 2013, 44 patients with metastatic renal cell carcinoma who received sunitinib at an oncology center of Cairo university hospitals were enrolled in this retrospective analysis. Results: The median age of the patients was 53 years, 22 (50%) having localized disease at presentation, while the remaining half of the patients presented with metastasis. At a median follow up of 19 months, 9 (21%) patients achieved partial remission, while disease was reported stable in 20 cases (45%) and progressive in 7 (16%), 4 (9%) being lost to follow up, and 4 (9%) had discontinued therapy due to toxicity. The median overall survival was 23 months (95%CI 15.2 - 30.9), while progression free survival was 12 months (95%CI 11.6 - 12.3). The most commonly reported non hematological grade 3 adverse events included mucositis (15.9%), hand-foot syndrome (13.6%), and fatigue (9%), while the predominant grade 3 or 4 laboratory abnormalities were neutropenia (6.8%), followed by anemia in 4.5% of patients. Conclusions: Our efficacy data were comparable to the published literature in terms of progression free survival and overall survival, while toxicity profile is different from Asian and western countries. However, sunitinib adverse events were manageable and tolerable in most of our Egyptian patients. -
Zhang, Bin;Qian, Jing;Chang, De-Hui;Wang, Yang-Min;Zhou, Da-Hai;Qiao, Gou-Mei 1977
Objective: The Von Hippel-Lindau syndrome (VHLD), an inherited neoplastic syndrome predisposing to central nervous system hemangioblastoma (CNS), pheochromocytoma (PCC), renal cell carcinoma(RCC), retinal hemangioma (RA) and renal cysts, is caused by mutations or deletions of the VHL tumor-suppressor gene. To assess VHL genotype-phenotype correlations with function of pVHL a gene mutation analysis of members in a Chinese family with non-syndromic PCCs and individuals with apparently sporadic pheochromocytoma (ASP) was performed. Materials and Methods: DNA samples of 20 members from the Chinese family with non-syndromic PCCs and 41 patients with ASP were analyzed by polymerase chain reaction and direct sequencing, confirmed by Taqman probe. Results: Three novel mutations (H125P, 623(^TTTGTtG) and R120T) were identified in the Chinese family and in 3 among 41 ASP patients. The mutations were all located in exon 2 of VHL gene encoding${\beta}$ -domain of pVHL. The tumor type in H125P carriers and R120T carriers was VHL type 2C. And 623(^TTTGTtG) carriers presented VHL type 2B or type 2C. Conclusions: VHL gene abnormalities were identified in the Chinese family with non-syndromic PCCs and patients with APS, resulting in dysfunction of pVHL. H125P and R120T could be associated with VHL type 2C, while 623(^TTTGTtG) might be linked with VHL type 2B or type 2C. Not only is the genetic analysis helpful for early diagnosis and treatment of patients with VHLD, it is also benefitial for research intoVHLD pathogenesis. -
Khodadost, Mahmoud;Yavari, Parvin;Babaei, Masoud;Mosavi-Jarrahi, Alireza;Sarvi, Fatemeh;Mansori, Kamyar;Khodadost, Behnam 1981
Background: Knowledge of cancer incidences is essential for cancer prevention and control programs. Capture-recapture methods have been recommended for reducing bias and increasing the accuracy of cancer incidence estimations. This study aimed to estimate the completeness of gastric cancer registration by the capture-recapture method based on Ardabil population-based cancer registry data. Materials and Methods: All new cases of gastric cancer reported by three sources, pathology reports, death certificates and medical records that reported to Ardabil population-based cancer registry in 2006 and 2008 were enrolled in the study. The duplicate cases based on the similarity of first name, surname and fathers names were identified between sources. The estimated number of gastric cancers was calculated by the log-linear method using Stata 12 software. Results: A total of 857 new cases of gastric cancer were reported from three sources. After removing duplicates, the reported incidence rates for the years 2006 and 2008 were 35.3 and 32.5 per 100,000 population, respectively. The estimated completeness calculated by log-linear method for these years was 36.7 and 36.0, respectively. Conclusions: These results indicate that none of the sources of pathology reports, death certificates and medical records individually or collectively fully cover the incident cases of gastric cancer. We can obtain more accurate estimates of incidence rates using the capture-recapture method. -
Irtiza, Syed;Samie, Amat Us;Ali, Shakir;Siddiqi, Mushtaq A;Naqash, Sameer H;Sameer, Aga Syed 1987
The aim of this research was to investigate the possible association between gastric carcinoma (GC) and polymorphisms of the IL-$1{\beta}$ gene in the Kashmiri population using peripheral blood DNA from 150 gastric carcinoma cases and 250 population controls with detailed data for clinicopathological characteristics of the disease. Two SNPs in the IL-$1{\beta}$ gene were selected for this study. Expression of IL-$1{\beta}$ was studied in 50 gastric carcinoma cases using immunohistochemistry and RT-PCR and then correlated with genotype. The frequency of the IL-$1{\beta}$ -511 C allele was significantly higher in the GC case group (53.3%) than in controls (45.4%) with an odds ratio (OR) of 0.73 and a P value of 0.03. Multivariate regression analysis showed associations of gastric carcinoma with mutant form of IL-$1{\beta}$ -511 TT (OR 0.309; P value <0.001) and the CC genotype of IL-$1{\beta}$ -31 (OR 0.313; P value of 0.002). Haplotype analysis of IL-$1{\beta}$ -31 and IL-$1{\beta}$ -511 showed decreased association of IL-$1{\beta}$ -31 T with IL-$1{\beta}$ -511 C with gastric carcinoma (OR 0.728; P value 0.03). Expression study of 50 samples by immunohistochemistry (IHC) and RT-PCR showed association with grade III and stage III+IV. After correlating the expression with polymorphism no association was found. -
Zhang, Ming-Qian;Lin, Xin;Li, Yan;Lu, Shuang 1993
Purpose: This analysis was conducted to evaluate the efficacy and safety of irinotecan based regimens as second-line chemotherapy in treating patients with small cell lung cancer. Methods: Clinical studies evaluating the efficacy and safety of irinotecan based regimens as second-line chemotherapy for patients with small cell lung cancer were identified using a predefined search strategy. Pooled response rates (RRs) of treatment were calculated. Results: In irinotecan based regimens as second-line chemotherapy, 4 clinical studies which including 155 patients with small cell lung cancer were considered eligible for inclusion. In all chemotherapy consisted of irinotecan with or without nedaplatin. Pooled analysis suggested that, in all patients, the pooled RR was 27.1% (42/155) in irinotecan based regimens. Nausea, vomiting, diarrhea and myelosuppression were the main side effects. No grade III or IV renal or liver toxicity was observed. No treatment related death occurred with the irinotecan based treatments. Conclusion: This systemic analysis suggests that irinotecan based regimens as second-line chemotherapy are associated with mild response rate and acceptable toxicity for patients with small cell lung cancer. -
Yanatatsaneejit, Pattamawadee;Boonsrang, Ajaree;Mutirangura, Apiwat;Patel, Vyomesh;Kitkumthorn, Nakarin 1997
Objective: To clarify the association between the p53 polymorphism at codon 72 and susceptibility to the sporadic keratocystic odontogenic tumor (KCOT). Design: One hundred KCOTs and 160 match-group healthy controls were genotyped to ascertain the frequency of the p53 codon 72 polymorphism using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), confirmed by direct sequencing. Results: The frequencies of the Pro/Pro, Arg/Pro, and Arg/Arg genotypes were 23.8%, 49.4%, and 26.9%, respectively, in the controls, while the KCOT cohort demonstrated 43.0%, 39.0%, and 18.0%, respectively. Further analysis suggested that p53 Pro could be a KCOT-susceptible allele (OR (95%CI)=1.77 (1.22 to 2.59), p=0.0024), with a sex-adjusted OR (95%CI) of 1.71 (1.17-2.50), p=0.0046. Moreover, the results indicated that p53 codon 72 Pro homozygous was associated with a two-fold risk of developing KCOT (adjusted OR (95%CI) =2.17(1.23-3.84), p=0.0062). Conclusions: The C/C genotype of P53 gene codon 72 increases the risk of developing sporadic KCOT and may be a useful tool for screening and diagnostic purposes. -
Tatli, Ali Murat;Urakci, Zuhat;Kalender, Mehmet Emin;Arslan, Harun;Tastekin, Didem;Kaplan, Mehmet Ali 2003
Background: Elevated serum alpha-fetoprotein (AFP) levels in adults are considered abnormal. This parameter is used mostly in the diagnosis and follow-up of hepatocellular carcinomas and yolk sac tumors. Among the other rare tumors accompanied with elevated serum AFP levels, gastric cancer is the most common. In this study, we evaluated the follow-up and comparison of the treatment and marker response of patients with metastatic gastric cancer who had elevated serum AFP levels. Materials and Methods: We performed a retrospective study, including all consecutive patients with advanced gastric cancer, who received systemic chemotherapy with elevated AFP level. Results: Seventeen metastatic gastric cancer patients with elevated AFP levels at the time of diagnosis were evaluated. Fourteen (82.4%) were males and three (17.6%) were females. The primary tumor localization was the gastric body in 8 (76.4%), cardia in 7 (41.2%), and antrum in 2 (11.8%). Hepatic metastasis was observed in 13 (76.4%) at the time of diagnosis. When the relationship of AFP levels and carcinoembryonic antigen (CEA) response of the patients with their radiologic responses was evaluated, it was found that the radiologic response was compatible with AFP response in 16 (94.1%) patients and with CEA response in 12 (70.6%); however, in 5 (29.4%) patients no accordance was observed between radiological and CEA responses. Conclusions: Follow-up of AFP levels in metastatic gastric cancer patients with elevated AFP levels may allow prediction of early treatment response and could be more useful than the CEA marker for follow-up in response evaluation. -
Shi, Jing;Zhuang, Yan;Liu, Yan;Yan, Cheng-Quan;Liu, Xian-Kui;Zhang, Ying 2009
Objective: Glutathione S-transferase M 1 (GSTM1) is implicated as a risk factor for prostate cancer. However, this issue is not clear in Chinese population. This systemic analysis was conducted to evaluate the effect of GSTM1 null genotypes on prostate cancer risk in Chinese. Methods: Published studies investigating the associations between GSTM1 null genotypes and the risk of prostate cancer in China were identified by using a predefined search strategy. Main statisticals were pooled and estimated according to the primarily reported data. Results: The prevalence of the GSTM1 null genotype was higher in prostate cancer patients than in controls, with significance. Conclusion: The GSTM1 null genotypes is associated with increased risk of prostate cancer in Chinese. -
Bahri, Narjes;Jajvandian, Roya;Bolandhemmat, Maryam;Najmabadi, Khadigeh Mirzaii 2013
Background: The aim of the study was to assess the extent of knowledge, attitudes and practical behavior of women in Bojnourd conerning the Pap smear test. Materials and Methods: This cross-sectional and population-based study was conducted with 1000 Iranian women aged 15-60 years old in Bojnourd city. In order to collect the data, a validated questionnaire was provided in four sections covering demographic information and questions about knowledge, attitude and practice about the Pap smear. Statistical analysis was performed with the Statistical Package for Social Sciences (version 17.0) applying a 0.05 significance level. Results: Evaluation of knowledge showed that 146 women (14.6%) had very weak, and 594 women (59.4%) had weak knowledge. In contrast, most of the women studied, 873 (87.3%), had a positive attitude toward the Pap smear test. According to the findings, 375 women (37.6%) had done this test so far. Findings indicated that the extent of knowledge had a meaningful relationship with the attitude status (p<0.0001). Also, there was a meaningful relationship between knowledge and practice, so that the weakest practice was seen in women who had weak knowledge (61.1%), (p<0.0001). Conclusions: According to findings of this research, most women do not have an appropriate knowledge about the necessity of having the Pap smear test, so that only a low percentage of women had undergone this test. -
Takeshige, Nobuyuki;Yin, Guang;Ohnaka, Keizo;Kono, Suminori;Ueki, Takashi;Tanaka, Masao;Maehara, Yoshihiko;Okamura, Takeshi;Ikejiri, Koji;Maekawa, Takafumi;Yasunami, Yohichi;Takenaka, Kenji;Ichimiya, Hitoshi;Terasaka, Reiji 2019
Much interest has been drawn to possible associations between vitamin D receptor (VDR) gene polymorphisms and colorectal cancer risk in conjunction with potentially protective effects of calcium and vitamin D. In a study of 685 cases of colorectal cancer and 778 community controls in Japan, we examined the associations of the FokI, BsmI, ApaI, and TaqI polymorphisms with colorectal cancer risk and effect modification by dietary calcium and vitamin D. Genotypes were determined by the PCR-RFLP method. The ApaI polymorphism seemed to be associated with a decreased risk of colorectal cancer, particularly of rectal cancer. The adjusted odds ratio of colorectal cancer for the ApaI AA and Aa genotypes combined versus the aa genotype was 0.83 (95% confidence interval [CI] 0.67-1.02), and the corresponding value for rectal cancer was 0.75 (95%CI 0.56-0.99). A decreased risk of colorectal cancer for the ApaI AA and Aa genotypes combined was more evident in individuals with high calcium intake (interaction p=0.055). The FokI polymorphism seemed to be associated with a decreased risk of colon cancer among those with high vitamin D intake (interaction p=0.09). The BsmI and TaqI polymorphisms were unrelated to colorectal cancer risk, and the null associations were not modified by calcium or vitamin D intake. In conclusion, the ApaI polymorphism may be associated with a decreased risk of colorectal cancer in Japanese, dependent on dietary calcium intake. -
Hu, Jun-Hong;Tang, Hong-Na;Ma, Yong-Ping;Wang, Chen-Yu;Yao, Kun-Hou;Zhang, Jun-Jie;Ren, Xue-Qun 2027
Background: Laparoscope-assisted gastrectomy in treating patients with gastric cancers developed with a background of highly invasive traditional surgery and is being increasingly performed in the Asian Pacific area. This study systemically investigated the technique and clinical results for comparison with traditional radical subtotal gastrectomy for gastric cancers. Methods: Clinical studies evaluating the effectiveness and side effects of laparoscope-assisted gastrectomy in treating patients with gastric cancers were identified using a predefined search strategy. Summary rates of effectiveness and side effects of laparoscope-assisted gastrectomy were calculated. Results: Thirteen clinical studies which including 1,412 patients with gastric cancer treated by laparoscope-assisted gastrectomy were considered eligible for inclusion. Systemic analysis showed that, for all patients, the pooled resection rate was 100%. Major adverse effects were anastomotic stenosis, abdominal abscess, abdominal bleeding, postoperative ileus. Treatment related death occurred in 0. 71% (10/1412). Conclusion: This systemic analysis suggests that laparoscope-assisted gastrectomy in treating patients with gastric cancers is associated with good curative rate and acceptable complications. -
Thongchot, Suyanee;Loilome, Watcharin;Yongvanit, Puangrat;Dokduang, Hasaya;Thanan, Raynoo;Techasen, Anchalee;Namwat, Nisana 2031
Intra-tumoral hypoxia is an environment that promotes tumor cell migration, angiogenesis and epithelial-mesenchymal transition that accounts for a major mechanism of metastasis. Chloroquine potentially offers a new therapeutic approach with an 'old' drug for effective and safe cancer therapies, as it exerts anti-metastatic activity. We investigated the inhibitory effect of chloroquine on cholangiocarcinoma (CCA) cell migration under cobalt chloride ($CoCl_2$ )-stimulated hypoxia. We showed that chloroquine suppressed CCA cell migration under hypoxic-mimicking conditions on exposure to$100{\mu}M$ $CoCl_2$ . Moreover, chloroquine stabilized the protein level of prolyl hydroxylase domain proteins (PHD-2) but reduced the levels of hypoxic responsive proteins such as hypoxia-inducible factor (HIF-$1{\alpha}$ ) and vascular endothelial growth factor (VEGF). It also suppressed epithelial mesenchymal transition (EMT) by increasing the ratio of E-cadherin to N-cadherin under hypoxic conditions. In conclusion, chloroquine can inhibit hypoxia-stimulated metastasis via HIF-$1{\alpha}$ /VEGF/EMT which may serve as a useful additional strategy for CCA therapy. -
Ozaksit, Gulnur;Tokmak, Aytekin;Kalkan, Hatice;Yesilyurt, Huseyin 2037
Background: Relationships between poor prognosis of ovarian malignancies and changes in complete blood count parameters have been proposed previously. In this work, we aimed to evaluate clinicopathologic features in adolescents with adnexal masses and sought to establish any predictive value of the platelet to lymphocyte ratio (PLR) in diagnosis. Materials and Methods: This retrospective study was conducted on 196 adolescent females with adnexal masses. Three groups were constituted with respect to clinical or histopathology results: group 1, non-neoplastic patients (n:65); group 2, neoplastic patients (n:68); and group 3 expectantly managed patients (n:63). The main parameters recorded from the hospital database and patient files were age, body mass index (BMI), chief symptoms, diameter of the mass (DOM), tumor marker levels, complete blood count values including absolute neutrophil, lymphocyte, and platelet counts, mean platelet volume, platelet distribution width, and platecrit, surgical features, and postoperative histopathology results. Results: The expectantly managed patients were younger than the other groups (p=0.007). The mean body mass index (BMI) was higher in the neoplastic group (p=0.016). Preoperative DOM, CA125, mean platelet volume and PLR were statistically significantly different between the groups (p<0.05). ROC curve analysis demonstrated that increased PLR (AUC, 0.609; p=0.011) and BMI (AUC, 0.611; p=0.011) may be discriminative factors in predicting ovarian neoplasms in adolescents preoperatively. When the cut-off point for the PLR level was set to 140, the sensitivity and specificity levels were found to be 65.7% and 57.6%, respectively. Conclusions: We suggest that beside a careful preoperative evaluation including clinical characteristics, ultrasonographic features and tumor markers, PLR may predict ovarian neoplasms in adolescents. -
Li, Qi-Wen;Chen, Hong-Bing;Li, Zhi-Yang;Shen, Peng;Qu, Li-Li;Gong, Lai-Ling;Xu, Hong-Pan;Pang, Lu;Si, Jin 2043
Background: Serum Golgi protein 73 (GP73) as a novel and potential marker for diagnosing hepatocellular carcinoma (HCC) have been found to be elevated in HCC patients and associated with clinical variables representing tumor growth and invasiveness. The aim of this study was to prepare a pair of monoclonal antibodys (mAbs) against GP73 and develop a newly designed double-antibody sandwich enzyme-linked immunosorbent assay (s-ELISA), which would be used in the detection of serum GP73 (sGP73) as well as in the diagnosis of HCC. Materials and Methods: Produced by prokaryotic expression, the purified recombinant GP73 (rGP73), produced by prokaryotic expression, was used to immunize the Balb/c mice. Two hybridoma cell lines against GP73 were obtained by fusing mouse Sp2/0 myeloma cells with spleen cells from the immunized mice. The titers of anti-GP73 mAb reached 1:243,000. Western blotting analysis and Immunohistochemistry staining revealed that anti-GP73 mAb could recognize GP73 protein. The double-antibody s-ELISA was successfully established and validated by 119 HCC and 103 normal serum samples. Results: showed that the detection limit of this method could reach 1.56 ng/ml, and sGP73 levels in HCC group (mean=190.6 ng/ml) were much higher than those of in healthy controls (mean=70.92 ng/ml). Conclusions: Results of our study not only showed that sGP73 levels of HCC patients were significantly higher than those of healthy controls, but also indicated that the laboratory homemade anti-GP73 mAbs could be the optimal tool used in evaluating sGP73 levels, which would provide a solid foundation for subsequent clinical applications. -
Milana, Mitric-Askovic;Marko, Erak;Miroslav, Latinovic;Tihomir, Dugandzija 2051
Background: Radiation therapy is a key part of the combined modality treatment for Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL), which can achieve locoregional control of disease. The 3D-conformal radiation oncology can be extended-field (EFRT), involved-field (IFRT) and involved node (INRT). New techniques have resulted in a smaller radiation field and lower dose for critical organs such as lung heart and breast. Materials and Methods: In our research, we made a virtual simulation for one patient who was treated in four different radiotherapeutic techniques: mantle field (MFRT), EFRT, IFRT and INRT. After delineatiion we compared dose-volume histograms for each technique. The fusion of CT for planning radiotherapy with the initial PET/CT was made using Softver Xio 4.6 in the Focal program. The dose for all four techniques was 36Gy. Results: Our results support the use of PET/CT in radiation therapy planning. With IFRT and INRT, the burden on the organs at risk is less than with MFRT and EFRT. On the other hand, the dose distribution in the target volume is much better with the latter. Conclusions: The aim of modern radiotherapy of HL and NHL is to reduce the intensity of treatment and therefore PET/CT should be used to reduce and not increase the amount of tissue receiving radiation. -
Basaran, Hamit;Koca, Timur;Cerkesli, Arda Kaymak;Arslan, Deniz;Karaca, Sibel 2055
Purpose: To present information about prognostic factors of gastric cancer patients treated in our Erzurum center including age, gender, tumour location, pathological grade, stage and the effect of treatment on survival. Materials and Methods: This retrospective study was performed on patients who applied to our clinic and diagnosed as gastric cancer. Age and gender of the patients, primary location, histopathological characteristics, TNM stage of the gastric cancers (GCs), treatment applied, oncological treatment modalities and survival outcomes were studied. A univariate analysis of potential prognostic factors was performed with the log-rank test for categorical factors and parameters with a p value < 0.05 at the univariate step were included in the multivariate regression. Results: A total of 228 patients with a confirmed diagnosis of gastric cancer were included in the study with a male/female ratio of 1.47. Median follow-up period was estimated as 22.3 (range, 3 to 96) months. When diagnosis of the patients at admission was analysed, stage III patients were most frequently encountered (n=147; 64.5%). One hundred and twenty-six (55.3%) underwent surgical treatment, while 117 (51.3%) were given adjuvant chemotherapy. Median overall survival time was 18.0 (${\pm}1.19$ ) months. Mean overall survival rates for 1, 2, 3 and 5 years were$68{\pm}0.031%$ ,$36{\pm}0.033%$ ,$24{\pm}0.031%$ and$15.5{\pm}0.036%$ , respectively. Univariate variables found to be significant for median OS in the multivariate analysis were evaluated with Cox regression analysis. A significant difference was found among TNM stage groups, location of the tumour and postoperative adjuvant treatment receivers (p values were 0.011, 0.025 and 0.001, respectively). Conclusions: This study revealed that it is possible to achieve long-term survival of gastric cancer with early diagnosis. Besides, in locally advanced GC patients, curative resection followed by adjuvant concomitant chemoradiotherapy based on the McDonald regimen was an independent prognostic factor for survival. -
Hao, Guang-Wei;Chen, Yu-Sheng;He, De-Ming;Wang, Hai-Yu;Wu, Guo-Hao;Zhang, Bo 2061
Background: Tumors are largely unable to metabolize ketone bodies for energy due to various deficiencies in one or both of the key mitochondrial enzymes, which may provide a rationale for therapeutic strategies that inhibit tumor growth by administration of a ketogenic diet with average protein but low in carbohydrates and high in fat. Materials and Methods: Thirty-six male BALB/C nude mice were injected subcutaneously with tumor cells of the colon cancer cell line HCT116. The animals were then randomly split into three feeding groups and fed either a ketogenic diet rich in omega-3 fatty acids and MCT (MKD group; n=12) or lard only (LKD group; n=12) or a standard diet (SD group; n=12) ad libitum. Experiments were ended upon attainment of the target tumor volume of$600mm^3$ to$700mm^3$ . The three diets were compared for tumor growth and survival time (interval between tumor cell injection and attainment of target tumor volume). Results: The tumor growth in the MKD and LKD groups was significantly delayed compared to that in the SD group. Conclusions: Application of an unrestricted ketogenic diet delayed tumor growth in a mouse xenograft model. Further studies are needed to address the mechanism of this diet intervention and the impact on other tumor-relevant parameters such as invasion and metastasis. -
Rauf, Muhammad Shahzad;Akhtar, Saad;Maghfoor, Irfan 2069
Background: Lymphoma is one of the most common malignancies affecting the young Saudi population. This disease has diversified pathologies and clinical stages that necessitate well optimized clinical management. Regular updates of epidemiological behavior of lymphoma from various parts of the world are available but studies from the Kingdom of Saudi Arabia (KSA) in this field are not consistent. Objectives: The aim of this study was to investigate the current trends in presentation and distribution of lymphoma with special reference to incidence and mortality, gender, age, histopathological subtypes, and clinical stages at King Faisal Specialist Hospital and Research Centre (KFSH&RC). Materials and Methods: Our study included lymphoma data from Saudi Cancer Registry, and relative comparison against KFSH&RC tumor registry data, Gulf country data and International Agency for Research on Cancer data. Results: Common tumors in the West (lung, colon, and prostate) were found to be much less frequent in KSA while leukemia, lymphoma and thyroid cancers were more common. Non-Hodgkin Lymphoma (NHL) ranked 3rd most common cancer with age-adjusted incidence of 6/100,000. Estimated age adjusted mortality was 4/100,000 in KSA. There was a peak rise in incidence of lymphoma in 1997-2007. Most common NHL was diffuse large B cell lymphoma at KFSH&RC. A total of 434 cases were diagnosed in 5 years with 55% of them at advanced stage and 35% demonstrating bulky disease and high risk. KFSH&RC registered 35% of Hodgkins and 21% of total NHL identified in entire Saudi Cancer Registry, 2009. Conclusions: Results of this study are very unique, and reveal diverse trends. The findings provide valuable insights in the understanding of current epidemiological features of lymphoma in this part of the world. -
Kabekkodu, Shama Prasada;Bhat, Samatha;Pandey, Deeksha;Varghese, Vinay Koshy;Shukla, Vaibhav;Ghosh, Supriti;Kushtagi, Pralhad;Bhat, Parvati;Gopinath, Puthiya Mundayat;Satyamoorthy, Kapaettu 2073
Background: The human papillomavirus (HPV) and its variants show wide geographical distribution and have been reported to cause cervical lesions. With cervical neoplasia as the leading cancer in Indian women, the aim of the present study was to evaluate the multiple infection HPV type distribution and variant genotypes in cervical samples from the coastal Karnataka region, India. Materials and Methods: A total of 212 samples were screened by nested polymerase chain reaction using PGMY9/11 and GP5+/6+ primers. HPV positive samples were sequenced to identify the types and a phylogenetic tree was constructed using the neighbor-joining method. Results: Sequence analysis identified a total of 14 HPV types distributed in 20%, 73.3% and 82.5% of non-malignant, pre-malignant [low grade squamous intraepithelial lesion (LSIL) and high grade squamous intraepithelial lesion (HSIL)] and cervical cancer samples. The distribution of high risk HPV in cancer samples was HPV 16, 76.4%, HPV18, 11.7%, HPV81, 2.9%, HPV31, 1.4%, HPV35, 1.4% and HPV 45, 1.4%. Multiple infections were observed in 11.8% of tumor samples with HPV 16 contributing to 62.5% of cases. In non-malignant samples, 20% of HPV positive samples were detected with HPV16, 82.3%, HPV33, 5.8% and HPV58, 5.8% and very low incidence of multiple infections. Comparative phylogenetic analysis of HPV variants identified 9 HPV sequences as new papillomavirus species, predominantly classified as European lineage type. Conclusions: The findings for HPV infections associated with progression of cervical cancer in coastal Karnataka region and HPV variant analysis provide baseline data for prevention and HPV vaccination programs. -
Tang, Zhen;Huang, Shu-Qiong;Liu, Jian-Ting;Jiang, Gui-Xiang;Wang, Chun-Mei 2081
Gecko is a kind of traditional Chinese medicine with remarkable antineoplastic activity. However, undefined mechanisms and ambiguity regarding active ingredients limit new drug development from gecko. This study was conducted to assess anti-angiogenic properties of the aqueous extracts of fresh gecko (AG) or macromolecular components separated from AG (M-AG). An enzyme-linked immunosorbent assay (ELISA) approach was applied to detect the vascular endothelial growth factor (VEGF) secretion of the tumor cells treated with AG or M-AG. The effect of AG or M-AG on vascular endothelial cell proliferation and migratory ability was analyzed by tetrazolium dye colorimetric method, transwell and wound-healing assays. Chick embryo chorioallantoic membrane (CAM) assays were used to ensure the anti-angiogenic activity of M-AG in vivo. The results showed that AG or M-AG inhibited the VEGF secretion of tumor cells, the relative inhibition rates of AG and M-AG being 27.2% and 53.2% respectively at a concentration of$20{\mu}L/mL$ . AG and M-AG inhibited the vascular endothelial (VE) cell proliferation with IC50 values of$11.5{\pm}0.5{\mu}L/mL$ and$12.9{\pm}0.4{\mu}L/mL$ respectively. The VE cell migration potential was inhibited significantly (p<0.01) by the AG (${\geq}24{\mu}L/mL$ ) or M-AG (${\geq}12\mu}L/mL$ ) treatment. In vivo, neovascularization of CAM treated with M-AG was inhibited significantly (p<0.05) at a concentration of${\geq}0.4{\mu}L/mL$ . This study provided evidence that anti-angiogenesis is one of the anti-tumor mechanisms of AG and M-AG, with the latter as a promising active component. -
Pirouzpanah, Mohammad Bagher;Sabzichi, Mehdi;Pirouzpanah, Saeed;Chavoshi, Hadi;Samadi, Nasser 2087
Nowadays herbal-derived medicines are attracting attention as new sources of drugs with few side effects. Silibinin is a flavonoid compound with chemotheraputic effects on different cancers such as examples in the prostate, lung, colon and breast. In the present study, the cytotoxic effects of silibinin on MCF7 breast cancer cells were investigated. Apoptosis was determined by flow cytometry and the impact of silibinin on the expression of pivotal genes including Bak, P53, P21, BRCA1, BCL-X1 and ATM was analyzed. Treatment for 24h had a significant dose-dependent inhibitory effect on cell growth (p<0.05) with dose- and time- dependent induction of apoptosis (p<0.05). In addition, there were significant increases in BRCA1, ATM, Bak and Bcl-XL gene expression at the mRNA level with different concentrations of silibinin for 24 or 48 h (p<0.05). Taken together, the results suggest that silibinin inhibits the proliferation and induces apoptosis of MCF-7 cells by down-regulating Bak, P53, P21, BRCA1, BCL-Xl and thus may be considered as an effective adjuvant drug to produce a better chemopreventive response for the cancer therapy. -
Wang, Liang;Wang, Ke-Feng;Chang, Bo-Yang;Chen, Xiao-Qin;Xia, Zhong-Jun 2093
In patients with multiple myeloma (MM), once-weekly intravenous injection or twice-weekly subcutaneous injection (SC) of bortezomib has been proven to offer non-inferior efficacy to standard twice-weekly intravenous administration, with an improved safety profile. However, whether once-weekly SC bortezomib can further reduce the incidence rate of peripheral neuropathy (PN) and not compromise the efficacy remains to be investigated. 25 patients of MM treated with once-weekly SC bortezomib were reviewed in this study. The median treatment cycles were 4 (range, 2-9 cycles). Complete response (CR) rate was 52%,${\geq}$ very good partial response (VGPR) rate was 72%, and${\geq}$ partial response (PR) rate was 84%. 1-year and 2-year PFS rate was 63.0% and 34.3%, respectively, and 2-year OS rate was 100%. Any grade of PN was reported in 9 patients (36.0%), with 7 patients (28.0%) had grade 1 PN, and 2 patients (8.0%) had grade 2 PN. No patients reported grade 3/4 PN in this cohort. In conclusion, once-weekly subcutaneous administration of bortezomib offers excellent efficacy with a further improved safety profile, especially with regard to PN. It needs to be validated in future prospective randomized trials. -
Li, Yong;Li, Da-Jiang;Chen, Jian;Liu, Wei;Li, Jian-Wei;Jiang, Peng;Zhao, Xin;Guo, Fei;Li, Xiao-Wu;Wang, Shu-Guang 2099
Objective: To explore the expression of$laminin{\gamma}2$ in extrahepatic cholangiocarcinoma (EHCC) tissues and its influence on tumor invasion and metastasis. Materials and Methods: Paraffin embedding samples of cancer, para-cancer, lymph node metastatic and hepatic metastatic tissues from 79 patients undergoing EHCC resection were collected. Expression of$laminin{\gamma}2$ was detected by immunohistochemistry and its relationship with clinical pathological characteristics and the prognosis of EHCC patients were analyzed. Results:$Laminin{\gamma}2$ showed negative staining in para-cancer tissues, but demonstrated a 51.9% (41/79) positive expression rate in extracellular matrix (ECM) or cytoplasm of EHCC tissues. In lymph node metastatic and distant metastatic nidi, expression of$laminin{\gamma}2$ was significantly higher than in the primary nidi (${\chi}^2=7.4173$ , P=0.0065;${\chi}^2=4.0077$ , P=0.0453). The expression was in obvious association with lymph node metastasis (P<0.01), but had no relevance with age, gender, tumor location, tumor stage, differentiation and distant metastasis in ECM (P>0.05), whereas it was in marked connection with lymph node and distant metastasis (P<0.05 or P<0.01), but had no relationship with age, gender, tumor location, tumor stage and differentiation in cytoplasm (P>0.05). However, the median survival time and median recurrent period of patients with positive expression of$laminin{\gamma}2$ in both cytoplasm and ECM of tumor cells, only in ECM and only in cytoplasm, were evidently lower than with negative expression of$laminin{\gamma}2$ in RCM and cytoplasm (P<0.05 or P<0.01). Further Cox regression analysis showed that the positive expression of$laminin{\gamma}2$ and the tumor differentiation were independent risk factors influencing the prognosis of EHCC patients. Conclusions: Abnormal expression of$laminin{\gamma}2$ may be closely associated with invasion and metastasis of tumor cells, and thus a potential molecular marker for prognosis of EHCC patients. -
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