Asian Pacific Journal of Cancer Prevention
아시아태평양암예방학회 (Asian Pacific Journal of Cancer Prevention)
- 월간
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- 1513-7368(pISSN)
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- 2476-762X(eISSN)
과학기술표준분류
- 보건의료 > 의약품/의약품개발
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.
KSCI제16권7호
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Wang, Wei-Jia;Lei, Yuan-Yuan;Mei, Jin-Hong;Wang, Chun-Liang 2591
Breast cancer is the most common cancer worldwide among women and the second most common cancer. Approximately 15-23% of breast cancers over-express human epidermal growth factor receptor2 (HER2), a 185-kDa transmembrane tyrosine kinase, which is mainly found at the cell surface of tumor cells. HER2-positive breast cancer, featuring amplification of HER2/neu and negative expression of ER and PR, has the three following characteristics: rapid tumor growth, lower survival rate, and better response to adjuvant therapies. Clinically, it is notable for its role in a pathogenesis that is associated with increased disease recurrence and acts as a worse prognosis. At the same time, it represents a good target for anti-cancer immunotherapy despite the prevalence of drug resistance. New treatments are a major topic of research, and a brighter future can be expected. This review discusses the role of HER2 in breast cancer, therapeutic modalities available and prognostic factors. -
Esfahani, Maryam;Ataei, Negar;Panjehpour, Mojtaba 2601
Prostate cancer, with a lifetime prevalence of one in six men, is the second cause of malignancy-related death and the most prevalent cancer in men in many countries. Nowadays, prostate cancer diagnosis is often based on the use of biomarkers, especially prostate-specific antigen (PSA) which can result in enhanced detection at earlier stage and decreasing in the number of metastatic patients. However, because of the low specificity of PSA, unnecessary biopsies and mistaken diagnoses frequently occur. Prostate cancer has various features so prognosis following diagnosis is greatly variable. There is a requirement for new prognostic biomarkers, particularly to differentiate between inactive and aggressive forms of disease, to improve clinical management of prostate cancer. Research continues into finding additional markers that may allow this goal to be attained. We here selected a group of candidate biomarkers including PSA, PSA velocity, percentage free PSA,$TGF{\beta}1$ , AMACR, chromogranin A, IL-6, IGFBPs, PSCA, biomarkers related to cell cycle regulation, apoptosis, PTEN, androgen receptor, cellular adhesion and angiogenesis, and also prognostic biomarkers with Genomic tests for discussion. This provides an outline of biomarkers that are presently of prognostic interest in prostate cancer investigation. -
Giridhar, Prashanth;Mallick, Supriya;Rath, Goura Kishore;Julka, Pramod Kumar 2613
Radiation induced lung injury has long been considered a treatment limiting factor for patients requiring thoracic radiation. This radiation induced lung injury happens early as well as late. Radiation induced lung injury can occur in two phases viz. early (< 6 months) when it is called radiation pneumonitis and late (>6 months) when it is called radiation induced lung fibrosis. There are multiple factors that can be patient, disease or treatment related that predict the incidence and severity of radiation pneumonitis. Radiation induced damage to the type I pneumocytes is the triggering factor to initiate such reactions. Over the years, radiation therapy has witnessed a paradigm shift in radiation planning and delivery and successfully reduced the incidence of lung injury. Radiation pneumonitis is usually a diagnosis of exclusion. Steroids, ACE inhibitors and pentoxyphylline constitute the cornerstone of therapy. Radiation induced lung fibrosis is another challenging aspect. The pathophysiology of radiation fibrosis includes continuing inflammation and microvascular changes due to pro-angiogenic and profibrogenic stimuli resembling those in adult bronchiectasis. General supportive management, mobilization of airway secretions, anti-inflammatory therapy and management of acute exacerbations remains the treatment option. Radiation induced lung injury is an inevitable accompaniment of thoracic radiation. -
Ramamoorthy, Venkataraghavan;Rubens, Muni;Saxena, Anshul;Shehadeh, Nancy 2619
There are several studies that relate oxidative damage as possible mechanism for many cancers. Many studies have also shown that anti-oxidants like selenium and vitamin E decrease the risk for prostate cancer. The main objective of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) study was to look for the benefits of selenium and vitamin E supplementation on prostate cancer. The study had a large sample size, stringent experimental conditions, very long duration, standardized laboratories for biochemical analyses and other factors that contribute to high external validity. The SELECT study failed to show any significant risk reduction for prostate cancers ascribable to selenium and vitamin E supplementations. Because of these conflicting results, many researchers argue about the methods used, supplementations administered (selenium and vitamin E) and indicators used for assessing levels of supplementations. We reviewed many epidemiological studies, clinical trials, and pre-clinical studies. With corroborative evidences we justify that SELECT study has a sound methodology and rationale. In lieu of the contrary results of the select study, researchers should focus on the probable mechanisms for these contrary findings and continue their search for newer and effective agents for prevention of prostate cancer. -
Firoozabadi, Mehdi Dehghani;Rahmani, Hossein 2629
Most cancer patients experience nausea and vomiting after surgery. Today, many methods of treatment have been developed and used for the control of such symptoms. The most important are drug therapy, relaxation, oxygen therapy and gas therapy. In addition, dexamethasone, massage therapy and using a Venturi mask have also proven effective. Due to the nature of gas consumption which leads to nausea it is recommended that use of N2O in the operating room be avoided or applied in combination with oxygen or other gases with fewer complications. -
Background: It has been proven that an individuals health behavior is determined through a series of processes. This study aimed to assess the stages of adoption of breast cancer screening, and to identify the factors relating to progress through these stages. Materials and Methods: There were 202 female participants aged 20-59 years who were living in Chungbuk, South Korea. They were informed of the study purpose and agreed to participate. Data were collected from October 2010 to January 2011 by assessing the breast cancer screening stage, health beliefs, socio-demographic factors, and other facilitating factors. The participant current stage of adoption of breast cancer screening was classified using the Precaution Adoption Process Model (PAPM), and the various PAPM stages were compared with each other to identify factors likely to determine progress between stages. The data were analyzed using the
${\chi}^2$ -test, ANOVA, Duncan test, and multiple logistic regression. Results: Approximately half of all participants were not on-schedule for breast self-examination and mammography (unaware, 9.4% and 11.4%, unengaged, 8.4% and 5.0%, undecided, 20.3% and 17.8%, decided not to act, 1.5% and 1.0%, decided to act, 13.4% and 15.3%, respectively). The factors likely to determine the progress from one stage to another were age, marital status, exposure to media information about breast cancer, self-efficacy, and perceived severity. Conclusions: These results suggest that it is necessary to develop a tailored message for breast cancer screening behavior. -
Okutur, Kerem;Bassulu, Nuray;Dalar, Levent;Aydin, Kubra;Bozkurt, Mustafa;Pilanci, Kezban Nur;Dogusoy, Gulen Bulbul;Tecimer, Coskun;Mandel, Nil Molinas;Demir, Gokhan 2645
Background: The phosphatidylinositol 3'-kinase/Akt (PI3K/Akt) pathway is a key regulator for HER2-overexpressing breast cancer, but data about whether activation of PI3K/Akt is associated with poor prognosis and resistance to trastuzumab therapy is controversial. In this study we investigated predictive and prognostic significance of expression of p27, Akt, PTEN and PI3K, which are components of the PI3K/Akt signaling pathway, in HER2-positive metastatic breast cancer (MBC), retrospectively. Materials and Methods: Fifty-four HER2-positive MBC patients who had received first-line trastuzumab-based therapy were recruited for the study group. All of the patient's breast tissue samples were examined for p27 and Akt expression. In addition, twenty-five patients with sufficient amount of tumor tissue were also examined for PTEN and PI3K expression. p27, Akt, PTEN and PI3K were evaluated by immunohistochemistry and their relationship with patient demographic features, tumor characteristics, response to trastuzumab-based treatment and survival outcomes were analyzed. Results: p27, Akt, PTEN and PI3K were positive in 25.9%, 70.4%, 24% and 96% of the cases, respectively. Nomne were significantly associated with response to trastuzumab and time to progression (TTP). A trend toward statistical significance for longer overall survival (OS) was found for PTEN-positive patients (p=0.058); there was no significant relationship between the other immunohistochemical variables and OS. When we analyzed groups regarding co-expression, the PTEN-negative/Akt-negative group had a significantly lower objective response rate (ORR) (20% vs 80%, p=0.023) and the PTEN-negative/p27-negative and PTEN-negative/Akt-negative groups had significantly lower median OS compared to other patients (26.4 months vs 76.1 months, p=0.005 and 25.6 months vs 52.0 months, p=0.007, respectively). Conclusions: p27, Akt, PTEN and PI3K expression is not statistically significantly associated with ORR, TTP and OS, individually. However, the combined evaluation of p27, Akt and PTEN could be helpful to predict the response to trastuzumab-based therapy and prognosis in HER2-positive MBC. -
Wided, Ben Ayoub Hizem;Hamouda, Boussen;Hamadi, Hsairi;Mansour, Ben Abdallah 2653
Nasopharyngeal carcinoma (NPC) is the second most common neoplasm of head and neck in Tunisia. The distribution is bimodal with a first period occurrence between 15 and 20 years old and a second peak at around 50 years of age. Undifferentiated carcinoma of nasopharynx type III (UCNT) is the predominant histological type (93.4%). Data of cancer registry of North Tunisia confirmed that it is an intermediate risk area for NPC with overall ASRs of 3.6 and 1.6/100,000 respectively in males and females. This study aimed to present the evolution of incidence rate of nasopharyngeal carcinoma over a period of 12 years (1994-2006). Data of cancer registry of North Tunisia (NTCR), covering half of the Tunisian population, were used to determine evolution of NPC incidence, calculated by 5 year periods. The estimated annual percentage change (EAPC) was used as an estimate of the trend. To best summarize the behavior or the data trend across years, we used a join-point regression program. Between 1994 and 2006, we observed negative annual average change of standardized incidence in men and women (-3.3%and -2.7%) also for the standardized incidences which showed a rather important decline (26.4% in males and 22.3% in females). The truncated age standardized incidence rate of NPC in adults aged of 30 years old and more (N= 1209) decreased by -0.4% per year from 1994 to 2006 over time in north Tunisia dropping from 6.09 to 4.14 person-years. However, the rate was relatively stable during this period among youths aged 0-29 years (N= 233) in both sexes. NPC demonstrated a favorable evolution from 1994-2006 probably due to a improvement in socioeconomic conditions. -
Liu, Ying;Zhou, Yan-Dong;Xiao, Yu-Li;Li, Ming-Hua;Wang, Yu;Kan, Xuan;Li, Qiu-Ying;Lu, Jian-Guang;Jin, De-Jun 2659
Background: To examine the expression of cysteine-rich 61 (Cyr61/CCN1) protein in laryngeal squamouscell carcinoma (LSCC) tissues, and its relationship with the tumor epithelial-mesenchymal transition (EMT), invasion, metastasis, and prognosis. Materials and Methods: Immunohistochemistry was used to detect the expressions of Cyr61, Vimentin (Vim), and E-cadherin (E-cad) in 88 cases of LSCC tissues and 30 cases of tumor-adjacent normal tissues. Vim and E-cad were used as mesenchymal and epithelial markers, respectively, to determine the relationship between Cyr61 expression and the EMT of LSCC cells. In addition, clinical and histopathological data were combined to analyze the relationship between the positive-expression rates of Cyr61, Vim and E-cad and LSCC invasion, metastasis and prognosis. Results: In LSCC tissues, Vim expression rate was significantly higher than that of the tumor-adjacent tissues, whereas E-cad expression rate was significantly lower than that of the tumor-adjacent tissues. The Vim expression rate was significantly higher in stages T3 and T4 than in stages T1 and T2 LSCC tissues, whereas E-cad expression rate was significantly lower in stages T3 and T4 than in stages T1 and T2 LSCC tissues. Compared to the group without lymph node metastasis, the Vim expression rate was significantly higher and the E-cad expression rate was significantly lower in the group with lymph node metastasis. The expression rate of Cyr61 was significantly higher in LSCC tissues than in the tumor-adjacent normal tissues. In addition, the Cyr61 expression rate was higher in stages T3 and T4 than in stages T1 and T2 LSCC, and higher in the group with lymph node metastasis than in the group without lymph node metastasis. The Vim expression rate was significantly higher in the Cyr61 positive group than in the Cyr61 negative group, whereas the E-cad expression rate was significantly higher in the Cyr61 negative group than in the Cyr61 positive group. Survival analysis indicated that survival rates of Cyr61 positive, Vim positive and E-cad negative groups were significantly lower than that of Cyr61 negative, Vim negative and E-cad positive groups, respectively. Conclusions: Cyr61 expression is closely associated with LSCC invasion and lymph node metastasis. Overexpression of Cyr61 may induce EMT and therefore leads to LSCC invasion and metastasis and poor prognosis. Cyr61 may become a new maker for clinical prediction of LSCC invasion and metastasis and a new target for LSCC treatment. -
Du, Yong;Chen, Xin;Lin, Xiu-Qing;Wu, Wei;Huang, Zhi-Ming 2665
CD4+CD25+regulatory T cells (Tregs) play a key role in regulation of immnue response and maintenance of self-tolerance. Studies have found Tregs could suppress tumor-specific T cell-mediated immune response and promote cancer progression. Depletion of Tregs can enhance antitumor immunity. Dendritic cells (DCs) are professional antigen-presenting cells and capable of activating antigen-specific immune responses, which make them ideal candidate for cancer immunotherapy. Now various DC vaccines are considered as effective treatment for cancers. The aim of this study was to evaluate variation of Tregs in BALB/C mice with hepatocellular carcinoma and investigate the interaction between tumor-derived Tregs, effector T cells (Teff) and splenic DCs. We found the percentages of Tregs/CD4+ in the peripheral blood of tumor-bearing mice were higher than in normal mice. Tumor-derived Tregs diminished the up-regulation of costimulatory molecule expression on splenic DCs, even in the presence of Teff cells and simultaneously inhibited IL-12 and$TNF-{\alpha}$ secretion by DCs. -
Baldane, Suleyman;Ipekci, Suleyman H;Sozen, Mehmet;Kebapcilar, Levent 2671
Thyroid cancer is the most prevalent endocrine cancer and is evident in nearly 5% of thyroid nodules. The correlation between mean platelet volume (MPV) and many other cancer types has been investigated previously. However, the correlation between papillary thyroid carcinoma (PTC) and MPV has not yet been studied in detail. The aim of this study was to examine whether MPV would be a useful inflammatory marker to differentiate PTC patients from cases of benign goiter and healthy controls. Preoperative MPV levels in patients with PTC were found to be significantly higher when compared with benign goiter patients and healthy controls ((respectively, 8.05 femtoliter (fl), 7.57 fl, 7.36 fl, p=0.001). After surgical treatment of PTC patients, a significant decrease in MPV levels was seen (8.05 fl versus 7.60 fl, p=0.005). ROC analysis suggested 7.81 as the cut-off value for MPV (AUC=0.729, sensitivity 60%, specificity 80%). In conclusion, maybe changes in MPV levels can be used as an easily available biomarker for monitoring the risk of PTC in patients with thyroid nodules, enabling early diagnosis of PTC. -
Mehta, Nisarg;Rathore, Ranjeet Singh;Pillai, Biju S;Sam, Mohan P;Moorthy, Krishna 2675
Background: Depending on various pathological factors, non muscle invasive bladder cancer (NMIBC) shows varying degrees of recurrence. The aim of this study was to determine the incidence of recurrence of NMIBS in our centre, study the influence of intrinsic tumour characteristics like grade, stage, size and number, and compare our results with data in the published literature. Materials and Methods: A hospital based retrospective study was conducted on patients who underwent treatment for NMIBC from 2011 to 2014. The factors studied were number, size, grade, stage and site for correlation with recurrence. Statistical analysis was performed using Medcalc version 12, using Pearson's Chi square test to ascertain associations between variables. Results: A total of 73 patients with NMIBC were studied of which 48 (65.8%) had low grade and 25 (34.2%) had high grade tumours. Some 38 patients (52.1%) had Ta tumours, 34 (46.6%) had T1 and one had CIS. Mean follow up was 34.3 months. Recurrence rates were found to be 33.3% in low grade and 52.0% in high grade tumours. The overall recurrence rate in our centre was 39.7%. Significant correlations were seen between stage and recurrence, with a rate of 15% for Ta and 63.3% for T1 tumours. Fourteen out of 21 bladder cancers (66.6%) with multiple tumours demonstrated recurrence (p=0.006). Grade, size and site had no influence. Conclusions: In our study, recurrence of NMIBC was found to be directly proportional to stage and number of primary tumours, but not grade, size and site. The incidence of recurrence of NMIBC both stage wise and grade wise in our centre was also low compared to the data in the published literature. -
Razis, Ahmad Faizal Abdull;Konsue, Nattaya;Ioannides, Costas 2679
Background: Phenethyl isothiocyanate (PEITC), the most comprehensively studied aromatic isothiocyanate, has been shown to act as an anti-cancer agent mainly through modulation of biotransformation enzymes responsible for metabolizing carcinogens in the human body. Humans are often exposed to carcinogenic factors, some of which through the diet, such as polycyclic aromatic hydrocarbon benzo[a]pyrene via the consumption of over-cooked meats. Inhibition of the enzymes responsible for the bioactivation of this carcinogen, for example CYP1A1, the major enzyme required for polycyclic aromatic hydrocarbons (PAHs) bioactivation, is recognized as a chemoprevention strategy. Objective: To evaluate the inhibitory effects of PEITC against benzo[a]pyrene-induced rise in rat liver CYP1A1 mRNA and apoprotein levels. Materials and Methods: Precision cut rat liver slices were treated with benzo[a]pyrene at 1 and$5{\mu}M$ in the presence of PEITC ($1-25{\mu}M$ ) for 24 hours, followed by determination of CYP1A1 mRNA and apoprotein levels using quantitative polymerase chain reaction and immunoblotting. Results: Findings revealed that PEITC inhibited benzo[a]pyrene-induced rise in rat liver CYP1A1 mRNA in a dose-dependent manner as well as the apoprotein levels of CYP1A. Conclusions: It was demonstrated that PEITC can directly inhibit the bioactivation of benzo[a]pyrene, indicating chemopreventive potential. -
Zhou, Yang-Chun;Zhao, Hai-Jian;Shen, Li-Zong 2685
To evaluate the clinical impact of preoperative serum CEA and CA19-9 on resectable gastric cancer (GC), a total of 1,075 consecutive cases with gastric adenocarcinoma were obtained retrospectively from January 2012 and December 2013 in a single tertiary hospital, and the relationships between serum CEA, CA19-9 and clinicopathologic features were investigated. Positive preoperative serum rates of CEA and CA19-9 were 22.4% and 12.3% respectively, levels significantly correlating with each other and depth of invasion, lymph node involvement, pTNM and stage. The CEA level also presented a remarkable association with lymphovascular invasion. Both CEA and CA19-9 positivity significantly and positively correlated with depth of invasion, nodal involvement, pTNM stage, lymphovascular invasion, tumor size and tumor location. Stratified analyses according to gender or tumor location showed preoperative CEA or CA19-9 had different associations with clinicopathologic features in different gender subgroups or location subgroups. Preoperative serum CA19-9 positivity may be more meaningful for tumor size rather than CEA. In conclusion, preoperative serum CEA and CA19-9 correlate with disease progression of GC, and may have applications in aiding more accurate estimation of tumor stage, decision of treatment choice and prognosis evaluation. -
Lv, Jun;Lv, Can-Qun;Mei, Ping;Qi, Shi-Mei 2693
The diagnostic value of membrane glycolipid biochemistry index, the lipid-bound sialic acid (LSA) and total sialic acid (TSA) in cerebrospinal fluid (CSF) was evaluated in 30 intracranial and 65 gastrointestinal tumors. The plasma LSA, TSA and red cell membrane sialic acid (R-SA) in were determined according to the method of Sevenmerhulm. Our results showed that the levels of LSA and TSA in CSF of intracranial tumor patients was higher than that of normal group(p<0.01). The concentration of TSA and LSA in patients with malignant glioma was higher than that of benign meningioma patients(P<0.01). No significance was found between intracranial halmatoma patients and normal control group for levels of membrane glycolipids (p>0.05). Results also found that the plasma LSA, TSA and R-SA of gastric carcinoma were significantly higher than those of control group (p<0.05); while no significant difference was found in the plasma LSA, TSA and R-SA levels between chronic gastritis, gastrohelcoma and normal control group (p>0.05). Plasma LSA, TSA and R-SA levels of gastric carcinoma patient were significantly higher than those of chronic gastritis patients and gastrohelcoma patients(p<0.05). It was also found that plasma LSA, TSA and R-SA contents were significantly higher in large intestine carcinoma patients than in benign in stestine tumor patients (p<0.05) while no significant difference was found between intestine benign tumor and normal control group (p>0.05). The levels of LSA, TSA and R-SA were obviously higher in the patients with metastasis than in the ones without (p<0.05.) The membrane glycolipid biochemistry index LSA and TSA in CSF are sensive markers for diagnosing intracranial tumors. For gastrointestinal malignant tumors the plasma LSA TSA and red blood cell membrane SA may be considered as auxiliary indicators for diagnosis. They can be used for distinguishing benign from malignant tumors. -
Alshammari, Fawaz Dabea;Khalifa, Amany M;Kosba, Ayman Ahmed;Khalil, Nuhar A;Ali, Safia M;Hassouna, Mona M;Elawad, Gamal Mohamed;Ginaw, Ibrahim Abdelmajeed;Ahmed, Hussain Gadelkarim 2697
Background: The aim of this study was to assess cancer awareness among medical students in Saudi Arabia toward tobacco and alcohol use as risk factors. Materials and Methods: A cross-sectional survey from October to December 2014, covering 1200 medical students, was performed. Results: Of the total, 975 (81.25%) responded. The male to female ratio was 1.00:7.125. 96/975 (9.8%) had smoked tobacco in their lifetime, and 51/975 (5.23%) were alcoholic beverage consumers. On asking them whether tobacco smoking and alcohol consumption can cause cancer, only 4/975 (0.4%) and 14/975 (1.43%) answered no for smoking and alcohol, respectively. Conclusions: The prevalence of smoking and alcohol use is very low among medical students, which might be due to high female contribution besides social stigma. The prevalence of second-hand smoke (SHS) was found to be very high in Hail region. -
Caliskan, Serife Gokce;Bilgin, Mehmet Dincer;Kozaci, Leyla Didem 2701
Chondrosarcoma, the second most common type of bone malignancy, is characterized by distant metastasis and local invasion. Previous studies have shown that treatment by pulsed electromagnetic field (PEMF) has beneficial effects on various cancer cells. In this study, we investigated the effects of PEMF applied for 3 and 7 days on the matrix metalloproteinase (MMP) levels in chondrosarcoma SW1353 cells stimulated with two different doses of$IL-1{\beta}$ . SW1353 cells were treated with (0.5 and 5 ng/ml)$IL-1{\beta}$ and PEMF exposure was applied either 3 or 7 days. MMP-9 and TIMP-1 levels were measured in conditioned media by enzyme-linked immunosorbent assay. The results were relative to protein levels. Statistical analyses were performed using one-way analysis of variance (ANOVA). P<0.05 was considered significant. PEMF treatment significantly decreased MMP-9 protein levels in human chondrosarcoma cells stimulated with 0.5 ng/ml$IL-1{\beta}$ at day 7, whereas it did not show any effect on cells stimulated with 5 ng/ml$IL-1{\beta}$ . There was no significant change in TIMP-1 protein levels either by$IL-1{\beta}$ stimulation or by PEMF treatment. The results of this study showed that PEMF treatment suppressed$IL-1{\beta}$ -mediated upregulation of MMP-9 protein levels in a dual effect manner. This finding may offer new perspectives in the therapy of bone cancer. -
Cingeetham, Anuradha;Vuree, Sugunakar;Jiwatani, Sangeeta;Kagita, Sailaja;Dunna, Nageswara Rao;Meka, Phanni Bhushann;Gorre, Manjula;Annamaneni, Sandhya;Digumarti, Raghunadharao;Sinha, Sudha;Satti, Vishnupriya 2707
Background: The human homologue of the mouse double minute 2 (MDM2) gene is a negative regulator of Tp53. MDM2-309T>G a functional promoter polymorphism was found to be associated with overexpression thereby attenuation of Tp53 stress response and increased cancer susceptibility. We have planned to evaluate the possible role of MDM2-309T>G polymorphism with risk and response to chemotherapy in AML. Materials and Methods: A total of 223 de novo AML cases and 304 age and sex matched healthy controls were genotyped for the MDM2-309T>G polymorphism through the tetra-primer amplification refractory mutation system (ARMS)-PCR method. In order to assess the functional relationship of -309T>G SNP with MDM2 expression level, we quantified MDM2 mRNA in 30 primary AML blood samples through quantitative RT-PCR. Both the (-309T>G) genotypes and the MDM2 expression were correlated with disease free survival (DFS) rates among patients who have achieved complete remission (CR) after first induction chemotherapy. Results: MDM2-309T>G polymorphism was significantly associated with AML development (p<0.0001). The presence of either GG genotype or G allele at MDM2-309 confered 1.79 (95% CI: 1.12-2.86; p<0.001) and 1.46 fold (95%CI: 1.14-1.86; p= 0.003) increased AML risk. Survival analysis revealed that CR+ve cases with GG genotype had significantly increased DFS rates (16months, p=0.05) compared to CR+ve TT (11 months) and TG (9 months) genotype groups. Further, MDM2 expression was also found to be significantly elevated in GG genotype patients (p=0.0039) and among CR+ve cases (p=0.0036). Conclusions: The MDM2-309T>G polymorphism might be involved in AML development and also serve as a good prognostic indicator. -
Zhang, Le;Jin, Tian-Bo;Gao, Ya;Wang, Hui-Juan;Yang, Hua;Feng, Tian;Chen, Chen;Kang, Long-Li;Chen, Chao 2713
Background: Possible associations between the single nucleotide polymorphism (SNP) rs8034191 in the aminoglycosidephosphotransferase domain containing 1 (AGPHD1) gene and lung cancer risk have been studied by many researchers but the results have been contradictory. Materials and Methods: A computerized search for publications on rs8034191 and lung cancer risk was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association between rs8034191 and lung cancer risk with 13 selected case-control studies. Sensitivity analysis, test of heterogeneity, cumulative meta-analysis, and assessment of bias were also performed. Results: A significant association between rs8034191 and lung cancer susceptibility was found using the dominant genetic model (OR=1.344, 95% CI: 1.285-1.406), the additive genetic model (OR=1.613, 95% CI: 1.503-1.730), and the recessive genetic model (OR=1.408, 95% CI: 1.319-1.503). Moreover, an increased lung cancer risk was found with all genetic models after stratification of ethnicity. Conclusions: The association between rs8034191 and lung cancer risk was significant using multiple genetic models, suggesting that rs8034191 is a risk factor for lung cancer. Further functional studies of this polymorphism and lung cancer risk are warranted. -
Liu, Qing-Hua;Shi, Mei-Lin;Bai, Jin;Zheng, Jun-Nian 2719
Objective: The aim of this study was to investigate the clinical significance of annexin a1 (ANXA1) and provide molecular evidence to support that decreased ANXA1 expression could enhance cancer migration and invasion in pancreatic ductal adenocarcinoma (PDAC). Materials and Methods: Immunohistochemistry of a tissue microarray with 162 surgically resected PDAC specimens was performed to examine the expression of ANXA1. We also investigated the relationship between ANXA1 expression and clinicopathological factors and prognosis of PDAC patients. We further studied the role of ANXA1 in PDAC cell proliferation, migration and invasion by cell proliferation assay, migration assay and matrigel invasion assay with reduced ANXA1 expression by RNAi. Western blotting was used to detect matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) expression. We also detected MMP-9 enzyme activity by gelatin zymography. Results: Decreased expression of ANXA1 was significantly associated with poor differentiation, lymph node metastasis and advanced TNM stage of PDAC patients (p<0.05). Moreover, decreased expression of ANXA1 was correlated with poor survival (p<0.05). Furthermore, we found that ANXA1 knockdown inhibited cell proliferation, induced G1 phase cell cycle arrest, increased PDAC cell migration and invasion capacity compared with controls. In addition, Western blotting showed that ANXA1 knockdown increased the MMP-9 protein level and decreased TIMP-1 expression. Gelatin zymography showed that MMP-9 enzyme activity was also elevated. Conclusions: Negative ANXA1 expression is a most unfavorable prognostic factor for PDAC patients. ANXA1 knockdown inhibits cell proliferation by inducing G1 phase cell cycle arrest and increases migration and invasion of PDAC cells through up-regulating MMP-9 expression and activity, implying that ANXA1 may serve as a promising prognostic biomarker and therapeutic target for PDAC. -
Khorramdelazad, Hossein;Bagheri, Vahid;Hassanshahi, Gholamhossein;Karami, Hormoz;Moogooei, Mozhgan;Zeinali, Masoud;Abedinzadeh, Mehdi 2725
Background: Transitional cell carcinoma (TCC) and prostate cancer are the most frequent cancers in the male genitourinary tract. Measurement of biological biomarkers may facilitate clinical monitoring and aid early diagnosis of TCC. The aim of the present investigation was to detect the mRNA levels of S100A12 and RAGE (receptor for advanced glycation end products) in patients suffering from bladder TCC. Materials and Methods: To explore the involvement of S100A12 and RAGE genes, total RNA was harvested from cancer tissues and samples obtained from normal non-tumorized urothelium of the same patients. Quantitative PCR (qPCR) was subsequently employed to determine the mRNA levels of S100A12 and RAGE. Results: The results showed that mRNA expression of S100A12 and RAGE was significantly up-regulated in the cancer tissue. Conclusions: According to the results presented in the current study, mRNA expression of S100A12 and RAGE might be as a useful biomarker for TCC. Therefore, this ligand-receptor axis possibly plays important roles in the development of TCC and may serve either as an early diagnostic marker or as a key factor in monitoring of response to treatment. More research is required concerning inhibition of the S100A12-RAGE axis in different cancer models. -
Public Awareness of Warning Signs and Symptoms of Cancer in Oman: A Community-Based Survey of AdultsAl-Azri, Mohammed;Al-Hamedi, Ibtisam;Al-Awisi, Huda;Al-Hinai, Mustafa;Davidson, Robin 2731
Background: The majority of deaths from cancer occur in low and middle income countries, partly due to poor public awareness of the signs and symptoms of cancer. Materials and Methods: A community based survey using the Cancer Awareness Measure (CAM) questionnaire was conducted in three different communities in Oman. Omani adults aged 18 years and above were invited to participate in the study. Results: A total of 345 responded from 450 invited participants (response rate=76.7%). The majority of respondents were unable to identify the common signs and symptoms of cancer identified in the CAM (average awareness was 40.6%). The most emotional barrier to seeking help was worry about what the doctor might find (223, 64.6%); a practical barrier was too busy to make an appointment (259, 75.1%) and a service barrier was difficulty talking to the doctor (159, 46.1%). The majority of respondents (more than 60% for seven out of ten symptoms) would seek medical help in two weeks for most signs or symptoms of cancer. Females were significantly more likely than males to be embarrassed (p<0.001), scared (p=0.001), and lack confidence talking about their symptoms (p=0.022). Conclusions: Urgent strategies are needed to improve public awareness of the signs and symptoms of cancer in Oman. This might leads to earlier diagnosis, improved prognosis and reduced mortality from cancer. -
Oh, Myueng Guen;Han, Mi Ah;Byeon, Yu Mi;Bae, Kyung Min;Choi, Seong-Hyung 2739
Background: More than 1 million cancer survivors reside in Korea. We here investigated activity limitations of cancer survivors compared to controls without a history of cancer. Materials and Methods: Using the 4th and 5th Korea National Health and Nutrition Examination Survey (2007-2012) data, we identified 1,155 adult cancer survivors. Activity limitations were defined as limitation in activities of daily living, experience of lying in a sickbed, and number of days lying in a sickbed during the last month. Descriptive analysis and multiple logistic regression compared these measures for survivors and controls by sex and age groups. Results: Approximately 29.4% of cancer survivors reported limitation in activities of daily living, 14.6% experienced lying in a sickbed, and 4.3% experienced more than 15 days lying in a sickbed during the last month. After controlling for demographic and health-related factors, cancer survivors were more likely to report activity limitation than controls. The associations were similar across sex and age groups. Conclusions: Cancer survivors have increased activity limitation compared to controls and these limitations persist across sex and age. Targeted interventions and improved management are essential for improving cancer survivor daily life. -
Guo, Li-Yan;Zhang, Shen;Suo, Zhen;Yang, Chang-Shuang;Zhao, Xia;Zhang, Guo-An;Hu, Die;Ji, Xing-Zhao;Zhai, Min 2745
Objective: To study the PLCE1 gene rs2274223 polymorphism with regard to esophageal cancer and its interaction with diet, lifestyle, psychological and environmental factors in Southwest Shandong province. Materials and Methods: A case series study (case-case) was conducted. Questionnaire data were collected and 3 ml-5ml venous blood was drawn for DNA extraction among the qualified research subjects. PLCE1 gene polymorphism was detected after PCR amplification of DNA. SPSS 13.0 software was used for statistical analysis of the data. Results: The three genotypes A/A, A/G and G/G PLCE1 gene rs2274223 was 31, 16 and 4 cases, accounting for 60.8%, 31.4%, 0.08% respectively. The difference of three genotypes (AA/GA/GG) proportion between negative and positive family history of patients was statistically significant,${\chi}^2=6.213$ , p=0.045. There was no statistically significant relationship between PLCE1 gene rs2274223 polymorphism and smoking, drinking,${\chi}^2=0.119$ , p=0.998, and${\chi}^2=1.727$ , p=0.786. There was no linkage of the three rs2274223 PLCE1 gene genotypes (AA/GA/GG) proportion with eating fried, pickled, hot, mildew, overnight, smoked, excitant food, eat speed, salt taste or not (p>0.05). or with living environment pollution and nine risk factors of occupational exposure (p>0.05). There was no statistically significant difference in TS scores between different genotype of rs2274223 PLCE1 gene. Conclusions: The PLCE1 rs2274223 polymorphism has a relationship with family history of esophageal cancer, but does not have any significant association with age, gender, smoking, alcohol drinking, food hygiene, eating habits, living around the environment and occupation in cases. -
Background: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can specifically induce apoptosis limited to various cancer cells, so this reagent is considered a promising medicine for cancer therapy. TRAIL also exerts effects on non-apoptotic signals, relevant to processes such as metastasis, autophagy and proliferation in cancer cells. However, the mechanisms of TRAIL-regulated non-apoptotic signals are unclear. The purpose of this study was to investigate MADD/CXCR7 effects in TRAIL-mediated breast cancer cell migration. Materials and Methods: The ability of MADD/CXCR7 to regulate MVP signaling in TRAIL-mediated breast cancer cells migration was evaluated by transwell migration assay, quantitative RT-PCR, Western blotting and knock down experiments. Results: In this study, we found that treatment with TRAIL resulted in induced expression levels of MADD and CXCR7 in breast cancer cells. Knock down of MADD followed by treatment with TRAIL resulted in increased cell migration compared to either treatment alone. Similarly, through overexpression and knockdown experiments, we demonstrated that CXCR7 also positively regulated TRAIL-inhibited migration. Surprisingly, knock down of MADD lead to inhibition of TRAIL-induced CXCR7 mRNA and protein expression and overexpression of CXCR7 lead to the reduction of MADD expression, indicating that MADD is an upstream regulatory factor of TRAIL-triggered CXCR7 production and a negative feedback mechanism between MADD and CXCR7. Furthermore, we showed that CXCR7 is involved in MADD-inhibited migration in breast cancer cells. Conclusions: Our work defined a novel signaling pathway implicated in the control of breast cancer migration.
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Almasi, Zeinab;Rafiemanesh, Hosein;Salehiniya, Hamid 2757
Background: Stomach cancer is the fourth most common cancer and the second leading cause of cancer-related death through the world. It is predicted that the number of new cancer cases will be more than 15 million cases by 2020. Regarding the lack of studies on this topic in the country, we have thoroughly examined the patho-epidemiology of stomach cancer in Iran. Materials and Methods: In this cross- sectional study data were collected retrospectively reviewing all new stomach cancer patients in Cancer Registry Center report of health deputy for Iran during a 6-year period (2003-2008). The study also examined the morphology of common stomach cancers. Trends in incidence and morphology underwent joinpoint regression analysis. Results: During the six-year period, a total of 35,171 cases of stomach cancer were registered. Average age standardized rate for females and males were equal to 7.1 and 15.1 per 100,000 persons, respectively. Most common histological type was adenocarcinoma, NOS with 21,980 cases (62.50%). The annual percentage change (APC) in age-standardized incidence rate (per 100,000) was increase in both females and males at 11.1 (CI: 4.3 to 18.3) and 9.2 (CI: 5.2 to 13.4), respectively. Conclusions: According to our results, the incidence of gastric cancer is increasing in Iran, so further epidemiological studies into the etiology and early detection are essential. -
Background: Cancer is an unnatural type of tissue growth in which the cells exhibit unrestrained division, leading to a progressive increase in the number of dividing cells. It is now the second largest cause of death in the world. The present study concerned antioxidant, anticancer and anticholinesterase activities and protocatechuic, catechin, caffeic acid, syringic acid, p-coumaric acid and o-coumaric concentrations in methanol extracts of flowers, fruits and seeds of Hypericum amblysepalum. Materials and Methods: Antioxidant properties including free radical scavenging activity and reducing power, and amounts of total phenolic compounds were evaluated using different tests. Protocatechuic, catechin, caffeic acid, syringic acid, p-coumaric acid and o-coumaric concentrations in extracts were determined by HPLC. Cytotoxic effects were determined using the MTT test with human cervix cancer (HeLa) and rat kidney epithelium cell (NRK-52E) lines. Acetyl and butyrylcholinesterase inhibitory activities were measured by by Ellman method. Results: Total phenolic content of H. amblysepalum seeds was found to be higher than in fruit and flower extracts. DPPH free radical scavenging activity of the obtained extracts gave satisfactory results versus butylated hydroxyanisole and butylated hydroxytoluene as controls. Reducing power activity was linearly proportional to the studied concentration range:
$10-500{\mu}g/mL\;LC_{50}$ values for H. amblysepalum seeds were 11.7 and 2.86 respectively for HeLa and NRK-52E cell lines. Butyryl-cholinesterase inhibitory activity was$76.9{\pm}0.41$ for seed extract and higher than with other extracts. Conclusions: The present results suggested that H. amblysepalum could be a potential candidate anti-cancer drug for the treatment of human cervical cancer, and good source of natural antioxidants. -
Shim, Hyung-Jeong;Lee, Ran;Shin, Min-Ho;Kim, Hee-Nam;Cho, Duck;Ahn, Hye-Ran;Kweon, Sun-Seog 2771
Background: Associations between ABO blood groups and risk of several malignancies have been reported, although there are limited data regarding hepatocellular carcinoma (HCC). The aim of this study was to investigate any possible association between the ABO genotype, especially blood group A, and HCC risk in Koreans. Materials and Methods: We conducted a case-control study of 1,538 patients with newly diagnosed HCC at Chonnam National University Hwasun Hospital and 1,305 randomly selected members of the general population. The ABO genotype was determined by multicolor real-time polymerase chain reaction (PCR) using displacing probes. Adjusted odds ratios (aORs) and their 95% confidence intervals (CIs) were calculated using logistic regression models with adjustment for gender, age, smoking, alcohol drinking, and hepatitis B and C status. Results: The risk of HCC in genotype AA was significantly higher than in OO (aOR=1.773, 95% CI=1.161-2.705). The risk in blood group A was also higher than in blood group O (aOR=1.448, 95% CI=1.005 1.897). No significant difference was found for the AA, BO, BB, and AB genotypes, or blood group B and AB. Conclusions: Blood group A and genotype AA showed the highest risks of HCC in a Korean population. No significant difference was found for the AO, BO, BB, and AB genotypes, or blood group B and AB. -
Liu, Jin-Kai;Chen, Wan-Cheng;Ji, Xiao-Zhen;Zheng, Wen-Hong;Han, Wei;An, Jing 2777
Background: Nestin is associated with neoplastic transformation. However, the mechanisms by which nestin contributes regarding invasion and malignancy of gastric adenocarcinoma (GAC) remain unknown. Recent studies have shown that the epithelial-mesenchymal transition (EMT) is important in invasion and migration of cancer cells. In the present study, we aimed to investigate the expression of nestin and its correlation with EMT-related proteins in GAC. Materials and Methods: The expression of nestin and EMT-related proteins was examined in GAC specimens and cell lines by immunohistochemistry and Western blotting. Clinicopathological features and survival outcomes were retrospectively analyzed. Results: Positive nestin immunostaining was most obviously detected in the cytoplasm, nucleus or both cytoplasm and nucleus of tumor cells in 19.2% (24/125) of GAC tissues, which was significantly higher than that in normal gastric mucosa tissues (1.7%, 1/60) (p=0.001). Nestin expression was closely related to several clinicopathological factors and EMT-related proteins (E-cadherin, vimentin and Snail) and displayed a poor prognosis. Interestingly, simultaneous cytoplasmic and nuclear nestin expression correlated with EMT-related proteins (E-cadherin, vimentin and Snail) (p<0.05) and lymph node metastasis (p=0.041) and a shorter survival time (p<0.05), but this was not the case with cytoplasmic or nuclear nestin expression. Conclusions: Nestin, particularly expression in both cytoplasm and nucleus, might be involved in regulating EMT and malignant progression in GAC, with potential as an unfavorable indicator in tumor diagnosis and a target for clinical therapy. -
Sun, Yang;Liu, Jia-Hua;Jin, Long;Sui, Yu-Xia;Han, Li-Li;Huang, Yin 2785
The purpose of the study was to determine the effects of autophagy related gene Beclin1 at different levels of expression on the sensitivity of cisplatin-resistant ovarian cancer cells (SKOV3/DDP) to different chemotherapeutics. In pSUPER-Beclin1 transfected cells, real-time fluorescence quantitative RT-PCR and Western blot analysis showed that expression was significantly inhibited. Flow cytometry revealed that the mean fluorescence intensity (MDC), reflecting autophagy, and cells in the G0/G1 phase were markedly reduced. When compared with the blank control group, inhibition of Beclin1 expression in SKOV3/DDP cells not only increased the rate of apoptosis following treatment with chemotherapeutics, but also increased the sensitivity. These findings suggest that Beclin1 expression plays an important role in chemotherapeutic agent-induced death of SKOV3/DDP cells. Inhibition of autophagy related gene Beclin1 expression in SKOV3/DDP cells may increase the rate of apoptosis and elevate the sensitivity to chemotherapeutics. -
Lee, Young Seok;Kim, Jin Ki;Ryu, Seoung Won;Bae, Se Jong;Kwon, Kang;Noh, Yun Hee;Kim, Sung Young 2793
In molecular-targeted cancer therapy, acquired resistance to gemcitabine is a major clinical problem that reduces its effectiveness, resulting in recurrence and metastasis of cancers. In spite of great efforts to reveal the overall mechanism of acquired gemcitabine resistance, no definitive genetic factors have been identified that are absolutely responsible for the resistance process. Therefore, we performed a cross-platform meta-analysis of three publically available microarray datasets for cancer cell lines with acquired gemcitabine resistance, using the R-based RankProd algorithm, and were able to identify a total of 158 differentially expressed genes (DEGs; 76 up- and 82 down-regulated) that are potentially involved in acquired resistance to gemcitabine. Indeed, the top 20 up- and down-regulated DEGs are largely associated with a common process of carcinogenesis in many cells. For the top 50 up- and down-regulated DEGs, we conducted integrated analyses of a gene regulatory network, a gene co-expression network, and a protein-protein interaction network. The identified DEGs were functionally enriched via Gene Ontology hierarchy and Kyoto Encyclopedia of Genes and Genomes pathway analyses. By systemic combinational analysis of the three molecular networks, we could condense the total number of DEGs to final seven genes. Notably, GJA1, LEF1, and CCND2 were contained within the lists of the top 20 up- or down-regulated DEGs. Our study represents a comprehensive overview of the gene expression patterns associated with acquired gemcitabine resistance and theoretical support for further clinical therapeutic studies. -
Bektas, Ilknur;Bektas, Murat;Selekoglu, Yasemin;Kudubes, Asli Akdeniz;Altan, Sema Sal;Ayar, Dijle 2801
Background: This study was conducted with the aim of determining how students' perceived smoking-cancer relationship and cardiovascular health attitudes affect childrens' views of smoking. Materials and Methods: The sample of this descriptive-cross sectional study comprised 574 subjects between the ages of 11-15. The data were collected using the Children's Cardiovascular Health Promotion Attitude Scale and the Children's Decisional Balance Measure for Assessing and Predicting Smoking Status. Correlation and logistic regression were used for analysis. Results: It was determined that a statistically significant relationship exists between the attitudes of children towards smoking and their ideas about the relationship of smoking with cancer, which is negative and low (r=-0.223). There was also a statistically significant relationship between their attitudes towards cardiovascular health and their attitudes towards smoking, again at a low level (r=0.257). It was determined that children with ideas about smoking and cancer were 9.4 times less likely to have positive/negative attitudes towards smoking, while positive attitudes towards cardiovascular health made negative attitudes towards smoking 3.9 times less likely. Conclusions: It was determined that the attitudes of students towards cardiovascular health and their perceptions of smoking and cancer reduced the positive perceptions towards smoking. -
Tong-ngam, Pirut;Roytrakul, Sittiruk;Sritanaudomchai, Hathaitip 2807
Scorpion venom peptides recently have attracted attention as alternative chemotherapeutic agents that may overcome the limitations of current drugs, providing specific cytotoxicity for cancer cells with an ability to bypass multidrug-resistance mechanisms, additive effects in combination therapy and safety. In the present study, BmKn-2 scorpion venom peptide and its derivatives were chosen for assessment of anticancer activities. BmKn-2 was identified as the most effective against human oral squamous cells carcinoma cell line (HSC-4) by screening assays with an$IC_{50}$ value of$29{\mu}g/ml$ . The BmKn-2 peptide killed HSC-4 cells through induction of apoptosis, as confirmed by phase contrast microscopy and RT-PCR techniques. Typical morphological features of apoptosis including cell shrinkage and rounding characteristics were observed in treated HSC-4 cells. The results were further confirmed by increased expression of pro-apoptotic genes such as caspase-3, -7, and -9 but decrease mRNA level of anti-apoptotic BCL-2 in BmKn-2 treated cells, as determined by RT-PCR assay. In summary, the BmKn-2 scorpion venom peptide demonstrates specific membrane binding, growth inhibition and apoptogenic activity against human oral cancer cells. -
Objective: To investigate the regulatory effect of curcumin on expression of signal transducer and activator of transcription 3 (STAT3) in skin squamous cell carcinoma tissues as well as possible mechanisms of curcumin in prevention and treatment of skin squamous cell carcinoma. Materials and Methods: Highly invasive A431 cells were treated with curcumin at various doses .The cytotoxic effects of treatment with 5, 10, 15, 20, 25, 30, 35, 40 and 50 umol/L curcumin for 24, 48 and 72 hours on A431 cells were measured by MTT assay. The invasion capacity of cells treated with 5, 10 and 15 umol/L curcumin was measured by Transwell test, while adhesive ability was assessed by cell adhesion assay. The effects of 5,10 and 15 umol/L curcumin on expression levels of STAT3 were determined by Western blotting and on transcription levels of STAT3 mRNA by RT-PCR. Results: Treatment with curcumin at a doses of more than 15 umol/L for more than 24 hour inhibited the growth of A431 cells in a time-and dose-dependent fashion (p<0.001). The doses of 15 umol/L and less for 24 hours showed no significant cytotoxic effects on the cells, survival rates being more than 85%.The invasion and adhesive abilities decreased gradually with the increasing curcumin concentration, 15 umol/L exerting the strongest inhibitory effects (p<0.05). Curcumin showed significant dose-dependent inhibitory effects on the transcription level of STAT3 mRNA (p<0.05). Conclusions: Curcumin may reduce the invasive ability of A431 cells by inhibiting the activation of STAT3 signal pathway and expression of STAT3 as a target gene in the pathway.
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Min, Li;Ma, Ruo-Lan;Yuan, Hua;Liu, Cai-Yun;Dong, Bing;Zhang, Cheng;Zeng, Yan;Wang, Li;Guo, Jian-Ping;Qu, Li-Ke;Shou, Cheng-Chao 2819
Combinations of multiple biomarkers representing distinct aspects of metastasis may have better prognostic value for breast cancer patients, especially those in late stages. In this study, we evaluated the protein levels of N-${\alpha}$ -acetyltransferase 10 protein (Naa10p), synuclein-${\gamma}$ (SNCG), and phosphatase of regenerating liver-3 (PRL-3) in 365 patients with breast cancer by immunohistochemistry. Distinct prognostic subgroups of breast cancer were identified by combination of the three biomarkers. The Naa10p+SNCG-PRL-3-subgroup showed best prognosis with a median distant metastasis-free survival (DMFS) of 140 months, while the Naa10p-SNCG+PRL-3+subgroup had the worst prognosis with a median DMFS of 60.5 months. Multivariate analysis indicated Naa10p, SNCG, PRL-3, and the TNM classification were all independent prognostic factors for both DMFS and overall survival (OS). The three biomarker combination of Naa10p, SNCG and PRL-3 performed better in patients with lymph node metastasis, especially those with more advanced tumors than other subgroups. In conclusion, the combined expression profile of Naa10p, SNCG and PRL-3, alone or in combination with the TNM classification system, may provide a precise estimate of prognosis of breast cancer patients. -
Tammasakchai, Achiraya;Chaiyasut, Chaiyavat;Riengrojpitak, Suda;Suwannalert, Prasit 2827
Oxidative stress is associated with colon carcinogenesis including aberrant crypt foci (ACF) formation and it plays an important role in pathophysiological changes in cancer cells. The aims of this study were to investigate the effects of dietary unpolished Thai rice (UTR) on ACF formation and dysplastic progression in azoxymethane (AOM)-treated rats. Anti-cancer efficacy of UTR regarding apoptotic induction and oxidative redox status in human colon cancer (CaCo-2) cells was also investigated. Rats given 20% and 70% of UTR in the diet showed significantly and dose-dependently decreased total number of ACF. UTR treatment also was strongly associated with the low percentage of dysplastic progression and mucin depletion. In addition, we found that UTR significantly induced cancer cell apoptosis, increased cellular oxidants, and decreased the level of GSH/GSSG ratio in CaCo-2 cells. Our study suggests that UTR supplementation may be a useful strategy for CRC prevention with the inhibition of precancerous progression, with induction of cancer cell apoptosis through redox alteration. -
Ozaslan, Ersin;Duran, Ayse Ocak;Bozkurt, Oktay;Inanc, Mevlude;Ucar, Mahmut;Berk, Veli;Karaca, Halit;Elmali, Ferhan;Ozkan, Metin 2833
Background: Repeating a prior chemotherapy (rechallenge therapy) is an option for selected patients with metastatic colorectal cancer, but there is very little evidence in the literature for this approach. Thus, we reviewed our registry to evaluate prognostic factors and survival of patients who received irinotecan and oxaliplatin-based regimens as rechallenge third and fourth-line therapy. Materials and Methods: Patients who received irinotecan-based or oxaliplatin-base regimen as first-line had been rechallenged with third-line or fourth-line therapy. These patients were selected from the database of Turkish mCRC registry archives between October 2006 and June 2013 and evaluated retrospectively for factors effecting progression free survival (PFS) and overall survival (OS) by the Kaplan-Meire and Cox-regression methods. Results: Thirty-nine patients were enrolled. The median duration of follow-up was 36 months (14-68 months). Thirty-one patients (76%) died during follow-up. In terms of rechallenge treatments, 29 patients had received third-line and 10 patients had received fourth-line. Response rate (RR) was found to be 12.9%, with stable disease in 19 (48.7%) patients. The median PFS was 6 months (95%CI=4.64-7.35 months) and the median OS was 11 months (95%CI=8.31-13.68 months). The factors effecting survival (PFS and OS) were only being PFS after first-line chemotherapy${\geq}12months$ (p=0.007, 95% CI=1.75-35.22 and p=0.004, 95%CI=1.44-7.11), both in univariate and multivariate analyses. Conclusions: This study indicates that rechallenge treatment could be a good option as a third or later line therapy in patients who had${\geq}12months$ PFS onreceiving first line therapy. -
Pongstaporn, Wanida;Pakakasama, Samart;Chaksangchaichote, Panee;Pongtheerat, Tanett;Hongeng, Suradej;Permitr, Songsak 2839
Background: MDR1, one of the most important drug-transporter genes, encodes P- glycoprotein (P-gp)-a transporter involved in protecting against xenobiotics and multi-drug resistance. The significance of the genetic background in childhood acute lymphoblastic leukemia (ALL) is not well understood. Materials and Methods: To evaluate whether C3435T and C1236T MDR1 polymorphisms are associated with the occurrence and outcome of ALL, 208 children with ALL (median age 5.0 yr) and 101 healthy Thai children were studied by polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) assay. Results: C3435T and C1236T MDR1 polymorphism are significantly associated with the high-risk group (OR= 2.6, 95%CI =1.164-5.808; P=0.028 and OR= 2.231, 95%CI =1.068-4.659; p=0.047, respectively), indicating that both may be candidates for molecular markers in the high-risk group of ALL. -
Fan, Yong-Gang;Zhai, Jing-Ming;Wang, Wei;Feng, Bing;Yao, Guo-Liang;An, Yan-Hui;Zeng, Chao 2845
Overexpression of interleukin (IL)-35 has been found in a variety of malignancies, but the expression status in gastric cancer has yet to be elucidated clearly. In the present study, positive expression of EBI3 and p35 was 63.3% and 70.0% of cases, respectively. EBI3 expression was strongly related with larger tumor size and invasion depth (P<0.05). Similarly, expression of p35 was also correlated with larger tumor size (P<0.05). These results indicate that IL-35 might be involved in growth of gastric cancer. Interestingly, EBI3 and p35 expressions were positive correlated with Ki-67 expression. Moreover, EBI3 immunoreactivity was associated with Bcl-2 staining. Our data suggest IL-35 is correlated with genesis of gastric cancer by regulating growth and apoptosis. -
Pan, Lin-Jiang;Zhong, Teng-Fei;Tang, Rui-Xue;Li, Ping;Dang, Yi-Wu;Huang, Su-Ning;Chen, Gang 2851
Background: Recent reports have shown that nuclear enriched abundant transcript 1 (NEAT1), a long noncoding RNA (lncRNA), contributes to the precise control of gene expression and is related to several human malignancies. However, limited data are available on the expression and function of NEAT1 in lung cancer. The major objective of the current study was to profile the expression and clinicopathological significance of NEAT1 in non-small cell lung cancers (NSCLCs). Materials and Methods: NEAT1 expression in 125 NSCLC cases and paired adjacent non-cancer tissues was assessed by real-time quantitative reverse transcription-PCR (qRT-PCR). Relationships between NEAT1 and clinicopathological factors were also investigated. Results: The relative level of NEAT1 was$6.98{\pm}3.74$ in NSCLC tissues, significantly elevated as compared to that of the adjacent non-cancer lung tissues ($4.83{\pm}2.98$ , p<0.001). The area under curve (AUC) of high expression of NEAT1 to diagnose NSCLC was 0.684 (95% CI: 0.619~0.750, p<0.001). NEAT1 expression was positively correlated with patient age (r=-2.007, p=0.047), lymphatic metastasis (r=-2.731, p=0.007), vascular invasion (r=-3.617, p=0.001) and clinical TNM stage (r=-4.134, p<0.001). Conclusions: This study indicates that NEAT1 might be associated with oncogenesis and progression in NSCLC, and suggests application in molecular targeted therapy. -
Kim, Yeonju;Yoo, Keun-Young;Goodman, Marc T 2857
Although the incidence of breast cancer in Asia remains lower than in North America, Western Europe, and Oceania, rates have been increasing rapidly during the past few decades, and Asian countries now account for 40% of breast cancer cases diagnosed worldwide. Breast cancer mortality has also increased among Asian women, in contrast to decreased mortality in Northern America, Western Europe, and Oceania. These increased rates are associated with higher prevalence of breast cancer risk factors (e.g., reduced parity, delayed childbirth, increased obesity) that have accompanied economic development throughout the region. However, Asian regions (western, south-central, south-eastern, and eastern) and countries differ in the types and magnitude of changes in breast cancer risk factors, and cannot be viewed as a single homogeneous group. The objective of this paper was to contrast the heterogeneous epidemiology of breast cancer by Asian regions and countries, and to suggest potential avenues for future research. -
Background: Urothelial carcinoma (UC) is a malignant neoplasm that most commonly occurs in the urinary bladder. The primary aim of this study was to evaluate the clinicopathologic features, recurrence and progression in patients with bladder urothelial cancer. Materials and Methods: The medical records of patients diagnosed with UC in the state pathology laboratory between January 2006 and July 2014 were retrospectively included. Carcinomas were categorized according to age, gender, histologic grade, tumor configuration, pathologic staging, recurrence status, and progression. Results: A total of 125 (113 men, 12 women) patients were examined. The mean age was 65.9 years and the male-to-female urothelial cancer incidence ratio was 9.4:1. Low-grade UCs were observed in 85 (68%) and high-grade in 40 (32%). A papillary tumor pattern was observed in 67.2% of the UCs. Cases were classified with the following pathological grades: 34 (27.2%) cases of pTa, 70 (56%) of pT1, and 21 (16.8%) of pT2. Recurrence occurred in 27 (21.6%) patients. Ten progressed to a higher stage (pT1 to pT2), and three cases to higher grade (low to high). We also analyzed the results separately for 70 (56%) patients 65 years of age and older. Conclusions: With early detection and diagnosis of precursor lesions in older patients, by methods such as standard urologic evaluation, urinary cytology, ultrasound scanning and contrast urography, and cystoscopy, in addition to coordinated efforts between pathologists and urologists, early diagnosis may reduce the morbidity and mortality of patients with urothelial carcinoma.
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Hazarika, Munlima;Iqbal, Asif;Krishnatreya, Manigreeva;Sharma, Jagannath Dev;Bhuyan, Chidananda;Saikia, Bhargab Jyoti;Roy, Partha Sarathi;Das, Rashmi;Nandy, Pintu;Kataki, Amal Chandra 2879
There is paucity of data on non Hodgkin's lymphoma (NHL) from our population in North-East India. In this retrospective study, patients were consecutively followed-up to see the clinic-pathological pattern of NHL, various responses, and pattern of relapses to first line treatment with chemotherapy. All patients in the present study received standard regimen of cyclophosphamde, doxorubicin, vincristine, prednisolone (CHOP) with or without rituximab (R-CHOP) as per our institutional protocol as first line therapy. Our study has shown that, in our adult population, the majority of NHL cases present with stage II and stage III disease and extra nodal involvement, B-cell lymphomas and diffuse large cell lymphomas being the most common subtypes. International prognostic index was a significant factor for varied responses to treatment. The majority of relapses after complete remission occurred in the first year. -
Jin, Ting;Zhang, Zhuo;Yang, Xue-Feng;Luo, Jun-Sheng 2883
Background: The calcium-binding S100A4 protein is involved in epithelial to mesenchymal transition, oncogenic transformation, angiogenesis, cytoskeletal integrity, mobility and metastasis of cancer cells. This study aimed to clarify the roles of S100A4 in genesis and progression of glioma. Materials and Methods: S100A4 expression was examined by real-time RT-CPR and Western blot in glioma and paired normal brain tissue (n=69), and compared with clinicopathological parameters of tumors. In addition, glioma U251 cells transfected with an S100A4-expressing plasmid were examined for proliferation by MTT, apoptosis by Annexin V-FITC, and migration and invasion with Transwell chambers. Results: Increased S100A4 mRNA expression was found in gliomas, compared with paired non-tumor tissue (p<0.001). Gradual elevation of overexpression of S100A4 was observed with increasing glioma grade (p<0.001). Astrocytoma showed lower S100A4 mRNA expression than oligodendrogliomas, with glioblastomas having highest values (p<0.001). Similar results were obtained for S100A4 protein, a positive link being found between mRNA and protein expression in gliomas (p<0.001). There was higher growth, lower apoptosis, stronger migration and invasion of S100A4 transfectants than control and mock transfected cells (p<0.001). Conclusions: These findings indicate that up-regulated S100A4 expression is positively linked to pathogenesis, progression and histogenesis of glioma by modulating proliferation, apoptosis, migration and invasion. -
Guan, Hui;Dong, Yuan-Li;Ding, Li-Jie;Zhang, Zi-Cheng;Huang, Wei;Liu, Cheng-Xin;Fu, Cheng-Rui;Zhu, Jian;Li, Hong-Sheng;Li, Miao-Miao;Li, Bao-Sheng 2889
Background: To investigate the impact of the breast size, shape, maximum heart depth (MDH), and chest wall hypotenuse (the distance connecting middle point of the sternum and the length of lung draw on the selected transverse CT slice) on the volumetric dose to heart with whole breast irradiation (WBI) of left-sided breast cancer patients. Materials and Methods: Fifty-three patients with left-sided breast cancer undergoing adjuvant intensity-modulated radiotherapy (IMRT) were enrolled in the study. The primary breast size and shape, MHD and DCWH (chest wall hypotenuse) were contoured on radiotherapy (RT) planning CT slices. The dose data of hearts were obtained from the dose-volume histograms (DVHs). Data were analyzed by one-way analysis of variance (ANOVA), Student's t-test and linear regression analysis. Results: Breast size was independent of heart dose, whereas breast shape, MHD and DCWH were correlated with heart dose. The shapes of breasts were divided into four types, as the flap type, hemisphere type, cone type and pendulous type with heart mean dose being$491.8{\pm}234.6cGy$ ,$752.7{\pm}219.0cGy$ ,$620.2{\pm}275.7cGy$ , and$666.1{\pm}238.0cGy$ , respectively. The flap type of breasts shows a strong statistically reduction in heart dose, compared to others (p=0.008 for V30 of heart). DCWH and MHD were found to be the most important parameters correlating with heart dose in WBI. Conclusions: More attention should be paid to the heart dose of non-flap type patients. The MHD was found to be the most important parameter to correlate with heart dose in tangential WBI, closely followed by the DCWH, which could help radiation oncologists and physicsts evaluate heart dose and design RT plan in advance. -
Srisuwan, Siriwan;Puapornpong, Pawin;Srisuwan, Supattra;Bhamarapravatana, Kornkarn;Suwannarurk, Komsun 2895
Background: In the years 2014, coverage rates of cervical cancer screening in Nakornnayok province accounted to 76.5%. This was lower than the government's specified goal of 80%. Community health volunteers are members of a Thai healthcare alliance established to help promoting healthcare service communication and collaboration at the primary level. Such village health volunteers (VHVs) are established in most villages. Objective: To assess the knowledge and attitudes of cervical cancer screening among VHVs. Materials and Methods: The subjects were 128 VHVs from four Nakornnayok sub-districts; namely KlongYai, Chomphol, Buangsan and Suksara, Thailand. The study was conducted from December 2014 to January 2015. The questionnaire was designed to assess the knowledge and attitude of cervical cancer screening provided by the VHVs. In addition, cervical cancer screening coverage rates of each area were collected. The demographic data, scores of knowledge, attitudes, practices and the cervical cancer screening coverage rates were analyzed by one-way ANOVA. Results: The questionnaire reliability was assessed as 0.81. The total knowledge and attitude scores were 10 and 15 points. The mean knowledge scores of KlongYai, Chomphol, Buangsan and Suksara were 6.8, 7.0, 6.5 and 9.0 points, respectively. The VHVs had a high level of overall knowledge about cervical cancer screening. The mean attitude scores were 12.4, 13.2, 13.4 and 13.1 points. VHVs had a positive attitude to the promotion of cervical cancer screening at the overall level. The percentages of VHVs promoting cervical cancer information in respective districts were 72.2, 94.3, 94.9 and 50.0. However, the cervical cancer screening coverage rates were 62.4%, 34.7%, 80.3% and 47.3% respectively. Conclusions: The knowledge, attitudes and percentages of promoting information of cervical cancer screening among VHVs in the four sub-districts were high but did not correlate with the cervical screening coverage rates for each area. VHVs needed to understand socio-cultural beliefs of the women in the target population and design suitable strategies to encourage higher cervical screening coverage. -
Polrit, Kornnika;Kamsa-ard, Siriporn;Jirapornkul, Chananya;Promthet, Supannee 2899
Background: Cervical cancer is one of the most common cancers among women worldwide, and in Thailand is the second most common cancer among women. In 2008, a national cervical cancer screening programme was implemented in Thailand, but coverage remains relatively low. Objectives: The purpose of the study was to investigate whether cervical cancer screening uptake is associated with the area of residency in Thailand. Materials and Methods: A case-control study was carried out in women aged 30 to 60 year-old, who live in Sikhiu district, Nakhon Ratchasima province, Thailand. Structured-questionnaires were used to interview 226 women (cases) who had attended cervical cancer screening in the last five years and 226 women (controls) who had not. Multiple logistic regression was used to investigate the association between the area of residency and cervical cancer screening uptake. Results: After controlling for parity, marital status and duration of hormonal contraceptive use, an association between the area of residence and cervical cancer screening uptake could not demonstrated ($OR_{adj}$ 1.27, 95%CI: 0.79, 2.04). Conclusions: We found no evidence to suggest remoteness to health care center led to lower cervical cancer screening uptake. -
Wong, Yoke Fui;Yusof, Mastura Md;Ishak, Wan Zamaniah Wan;Alip, Adlinda;Phua, Vincent Chee Ee 2903
Background: Head and neck cancer (HNC) is the eighth most common cancer as estimated from worldwide data. The incidence of HNC in Peninsular Malaysia was reported as 8.5 per 100,000 population. This study was aimed to determine the treatment outcomes for HNC patients treated in the Oncology Unit of University Malaya Medical Centre (UMMC). Materials and Methods: All newly diagnosed patients with squamous cell carcinoma of head and neck (HNSCC) referred for treatment to the Oncology Unit at UMMC from 2003-2010 were retrospectively analyzed. Treatment outcomes were 5-year overall survival (OS), cause specific survival (CSS), loco-regional control (LRC) and radiotherapy (RT) related side effects. Kaplan-Meier and log rank analyses were used to determine survival outcomes, stratified according to American Joint Committee on Cancer (AJCC) stage. Results: A total of 130 cases were analysed. Most cases (81.5%) were at late stage (AJCC III-IVB) at presentation. The 5-year OS for the whole study population was 34.4% with a median follow up of 24 months. The 5-year OS according to AJCC stage was 100%, 48.2%, 41.4% and 22.0% for stage I, II, III and IVA-B, respectively. The 5-year overall CSS and LCR were 45.4% and 55.4%, respectively. Late effects of RT were documented in 41.4% of patients. The most common late effect was xerostomia. Conclusions: The treatment outcome of HNSCC at our centre is lagging behind those of developed nations. Efforts to increase the number of patients presenting in earlier stages, increase in the use of combined modality treatment, especially concurrent chemoradiotherapy and implementation of intensity modulated radiotherapy, may lead to better outcomes for our HNC patients. -
Wang, Juan;Zhang, Yuan-Yuan;Cheng, Jian;Zhang, Jing-Ling;Li, Bao-Sheng 2909
Objective: To investigate the protective effect of quercetin on radiation induced lung injury (RILI) and related mechanisms. Materials and Methods: Mice treated with radiation and/or quercetin were sacrificed at 1-8 weeks after irradiation under anesthesia. Lung tissues were collected for histological examination. Immunohistochemistry (IHC) and Western blotting were performed to detect the protein expression of nuclear factor-${\kappa}B$ ($NF-{\kappa}B$ ) and Mitogen-activated protein kinases (MAPK) pathway. Results: Hematoxylin and eosin (HE) staining showed that radiation controls displayed more severe lung damage than quercetin groups, either high or low dose. Results of IHC and Western blotting demonstrated the expression level of$NF-{\kappa}B$ to be decreased and that of an inhibitor of$NF-{\kappa}B$ ($I{\kappa}b-{\alpha}$ ) to be increased by the quercetin intervention compared with the radiation control group. Numbers of JNK/SAPK, p38 and p44/p42 positive inflammatory cells were decreased in the radiation+quercetin injection group (P<0.05). Conclusions: Quercetin may play a radio-protective role in mice lung via suppression of$NF-{\kappa}B$ and MAPK pathways. -
Xiao, Bing-Kun;Yang, Jian-Yun;Dong, Jun-Xing;Ji, Zhao-Shuai;Si, Hai-Yan;Wang, Wei-Lan;Huang, Rong-Qing 2915
Background: Some recent clinical trials have been conducted to evaluate a combination of EGFR- TKI with chemotherapy for advanced NSCLC patients as second-line therapy, but the results on the efficacy of such trials are inconsistent. The aim of this meta-analysis was to evaluate the efficacy and safety of combination of EGFR-TKI and chemotherapy for patients with advanced NSCLC who failed first-line treatment. Materials and Methods: We searched relative trials from PubMed, EMBASE, ASCO Abstracts, ESMO Abstracts, Cochrane Library and Clinical Trials.gov. Outcomes analyzed were overall response rate (ORR), progression- free survival (PFS), overall survival (OS) and major toxicity. Results: Seven trails eventually were included in this meta-analysis, covering 1,168 patients. The results showed that the combined regimen arm had a significant higher ORR (RR 1.76 [1.16, 2.66], p=0.007) and longer PFS (HR 0.75 [0.66-0.85], p<0.00001), but failed to show effects on OS (HR 0.88 [0.68-1.15], p=0.36). In terms of subgroup results, continuation of EGFR-TKI in addition to chemotherapy after first-line EGFR-TKI resistance confered no improvement in ORR (RR 0.95 [0.68, 1.33], p=0.75) and PFS (HR 0.89[0.69, 1.15], p=0.38), and OS was even shorter (HR1.52 [1.05-2.21], p=0.03). However, combination therapy with EGFR-TKI and chemotherapy after failure of first-line chemotherapy significantly improved the ORR (RR 2.06 [1.42, 2.99], p=0.0002), PFS (HR 0.71 [0.61, 0.82], p<0.00001) and OS (HR 0.74 [0.62-0.88], p=0.0008), clinical benefit being restricted to combining EGFR-TKI with pemetrexed, but not docetaxel. Grade 3-4 toxicity was found at significantly higher incidence in the combined regimen arm. Conclusions: Continuation of EGFR-TKI in addition to chemotherapy after first-line EGFR-TKI resistance should be avoided. Combination therapy of EGFR-TKI and pemetrexed for advanced NSCLC should be further investigated for prognostic and predictive factors to find the group with the highest benefit of the combination strategy. -
Deblakshmi, Raj Kumari;Deka, Manab;Saikia, Anjan Kumar;Sharma, Bir Kumar;Singh, Nidhi;Das, NN;Bose, Sujoy 2923
Background: Gallbladder carcinoma (GBC) has been stated as an Indian disease, with the highest number of cases being reported from certain districts of northeast India, which has an ethnically distinct population. Unfortunately there are no scientific reports on the underlying molecular mechanisms associated with the pathogenesis of the disease from this region. Aim: The present study evaluated the role of differential expression of human telomerase reverse transcriptase (hTERT) in the development of gall bladder anomalies. Materials and Methods: Blood and tissue samples were collected from patients undergoing routine surgical resection for clinically proven cases of gallbladder disease {cholelithiasis (CL, n=50), cholecystitis (CS, n=40) and GBC (n=30) along with adjacent histopathologically proved non-neoplastic controls (n=15)} with informed consent. Whole blood was also collected from age and sex matched healthy controls (n=25) for comparative analysis. Differential hTERT mRNA expression was evaluated by semi-quantitative rt-PCR and real-time PCR based analysis using${\beta}$ -actin as an internal control. Evaluation of differential hTERT protein expression was studied by Western blot analysis and immunoflourescence. Statistical analysis for differential expression and co-relation was performed by SPSSv13.0 software. Results: Gallbladder anomalies were mostly prevalent in females. The hTERT mRNA and protein expression increased gradiently from normalHaque, Shafiul;Mandal, Raju K;Akhter, Naseem;Panda, Aditya K;Hussain, Arif;Khan, Saif;Lohani, Mohtashim 2929
Endothelial nitric oxide synthase (eNOS or NOS3) produces nitric oxide and genetic polymorphisms of NOS3 gene play significant roles in various processes of carcinogenesis. The results from published studies on the association between NOS3 G894T and NOS3 intron 4 (4a/b) polymorphisms and cancer risk are conflicting and inconclusive. However, i n order to assess this relationship more precisely, a meta-analysis was performed with PubMed (Medline), EMBASE and Google web searches until February 2014 to select all published case-control and cohort studies. Genotype distribution data were collected to calculate the pooled odd ratios (ORs) and 95% confidence intervals (CIs) to evaluate the strength of association. A total of 10,546 cancer cases and 10,550 controls were included from twenty four case-control studies for the NOS3 G894T polymorphism. The results indicated no significant association with cancer risk as observed in allelic (T vs G: OR=1.024, 95%CI=0.954 to 1.099, p=0.508), homozygous (TT vs GG: OR=1.137, 95%CI=0.944 to 1.370, p=0.176), heterozygous (GT vs GG: OR=0.993, 95%CI=0.932 to 1.059, p=0.835), recessive (TT vs GG+GT: OR=1.100, 95%CI=0.936 to 1.293, p=0.249) and dominant (TT+GT vs GG: OR=1.012, 95%CI=0.927 to 1.105, p=0.789) genetic models. Similarly, a total of 3,449 cancer cases and 3,691 controls were recruited from fourteen case-control studies for NOS3 4a/b polymorphism. Pooled results indicated no significant association under allelic (A vs B: OR=0.981, 95%CI=0.725 to 1.329, p=0.902), homozygous (AA vs BB: OR=1.166, 95%CI=0.524 to 2.593, p=0.707), heterozygous (BA vs BB: OR=1.129, 95%CI=0.896 to 1.422, p=0.305), dominant (AA+BA vs BB: OR=1.046, 95%CI=0.779 to 1.405, p=0.763) and recessive (AA vs BB+BA: OR=1.196, 95%CI=0.587 to 2.439, p=0.622) genetic contrast models. This meta-analysis suggests that G894T and 4a/b polymorphisms of NOS3 gene are not associated with increased or decreased risk of overall cancer.Hussain, Arif;Sharma, Chhavi;Khan, Saniyah;Shah, Kruti;Haque, Shafiul 2939
Many of the anti-cancer agents currently used have an origin in natural sources including plants. Aloe vera is one such plant being studied extensively for its diverse health benefits, including cancer prevention. In this study, the cytotoxic potential of Aloe vera crude extract (ACE) alone or in combination with cisplatin in human breast (MCF-7) and cervical (HeLa) cancer cells was studied by cell viability assay, nuclear morphological examination and cell cycle analysis. Effects were correlated with modulation of expression of genes involved in cell cycle regulation, apoptosis and drug metabolism by RT-PCR. Exposure of cells to ACE resulted in considerable loss of cell viability in a dose- and time-dependent fashion, which was found to be mediated by through the apoptotic pathway as evidenced by changes in the nuclear morphology and the distribution of cells in the different phases of the cell cycle. Interestingly, ACE did not have any significant cytotoxicity towards normal cells, thus placing it in the category of safe chemopreventive agent. Further, the effects were correlated with the downregulation of cyclin D1, CYP 1A1, CYP 1A2 and increased expression of bax and p21 in MCF-7 and HeLa cells. In addition, low dose combination of ACE and cisplatin showed a combination index less than 1, indicating synergistic growth inhibition compared to the agents applied individually. In conclusion, these results signify that Aloe vera may be an effective anti-neoplastic agent to inhibit cancer cell growth and increase the therapeutic efficacy of conventional drugs like cispolatin. Thus promoting the development of plant-derived therapeutic agents appears warranted for novel cancer treatment strategies.Wan, Han-Feng;Zhang, Bin;Yan, Dan-Gui;Xu, Zhen-Gang 2947
Background: The phenomenon of occult carcinoma maybe observed in patients with clinically unilateral papillary thyroid microcarcinoma (PTMC). Although many studies have reported that the$BRAF^{T1799A}$ mutation is associated with aggressive PTMC, the relationship between$BRAF^{T1799A}$ mutation and occult carcinoma is unclear. The aim of this study was to investigate the risk factors, including$BRAF^{T1799A}$ mutation, for occult contralateral carcinoma in clinically unilateral PTMC accompanied by benign nodules in the contralateral lobe. Materials and Methods: From January 2011 to December 2013, we prospectively enrolled 89 consecutive PTMC patients with clinically unilateral carcinoma accompanied by benign nodules in the contralateral lobe who received a total thyroidectomy and cervical lymph node dissection.$BRAF^{T1799A}$ mutation was tested by pyrosequencing on postoperative paraffin specimens. The frequency and predictive factors for occult contralateral carcinoma were analyzed with respect to the following variables: age, gender, family history, tumor size, presence of Hashimoto thyroiditis, extrathyroidal extension, central lymph node metastasis, multifocality of primary tumor, or$BRAF^{T1799A}$ mutation. Results: A total of 36 patients (40.4%) had occult PTMC in the contralateral lobe. The median diameter of the occult tumors was$0.33{\pm}0.21cm$ . The$BRAF^{T1799A}$ mutation was found in 38 cases (42.7%). According to the univariate analysis, there were no significant differences between the presence of occult contralateral carcinoma and age, gender, family history, tumor size, presence of Hashimoto thyroiditis, extrathyroidal extension, central lymph node metastasis, multifocality of primary tumor, or$BRAF^{T1799A}$ mutation. Conclusions: Using current methods, it is difficult to preoperatively identify patients with PTMC, and further research is needed to determine predictive factors for the presence of occult contralateral carcinoma in patients with unilateral PTMC.Li, Yan;Miao, Li-Yun;Xiao, Yong-Long;Huang, Mei;Yu, Min;Meng, Kui;Cai, Hou-Rong 2953
Although associations between thioredoxin interacting protein (TXNIP) and cancers have been recognized, the effects of TXNIP on non-small cell lung cancer (NSCLC) prognosis remained to be determined in detail. In addition, while hypoxia is a key characteristic of tumor cell growth microenvironment, the effect of hypoxia on TXNIP expression is controversial. In this study, formaldehyde fixed and paraffin embedded (FFPE) samples of 70 NSCLC patients who underwent resection between January 2010 and December 2011 were obtained. Evaluation of TXNIP and hypoxia inducible factor-$1{\alpha}$ ($HIF-1{\alpha}$ ) protein expression in FFPE samples was made by immunohistochemistry. By Kaplan-Meier method, patients with high TXNIP expression demonstrated a significantly shorter progression free survival (PFS) compared with those with low TXNIP expression (18.0 months, 95%CI: 11.7, 24.3 versus 23.0 months, 95%CI: 17.6, 28.4, P=0.02). High TXNIP expression level was also identified as an independent prognostic factor by Cox regression analysis (adjusted hazard ratio: 2.46; 95%CI: 1.08, 5.56; P=0.03). Furthermore, TXNIP expression was found to be significantly correlated with$HIF-1{\alpha}$ expression (Spearman correlation=0.67, P=0.000). To further confirm correlations, we established a tumor cell hypoxic culture model. Expression of TXNIP was up-regulated in all three NSCLC cell lines (A549, SPC-A1, and H1299) under hypoxic conditions. This study suggests that hypoxia induces increased TXNIP expression in NSCLC and high TXNIP expression could be a poor prognostic marker.de Almeida, Gibran Sarmento;Almeida, Layze Amanda Leal;Araujo, Gilmara Marques Rodrigues;Weller, Mathias 2959
The incidence and mortality rates of breast cancer in Northeast Brazil are increasing and little is known about prevailing reproductive factors contributing to this increase. A case-control study was conducted in a public hospital of Campina Grande, state of$Para{\acute{i}}ba$ , including 81 women with diagnosed invasive breast cancer and 162 age matched (${\pm}5years$ ) controls. Binominal logistic regression analysis was applied to estimate odds ratio (OR) and confidence intervals (CI) of risk factors. In this model, age at menarche${\leq}12$ (OR=2.120; CI: 1.043-4.308; p=0.038), single parity (OR=3.748; CI: 1.459-9.627; p=0.06) and reproductive period >10 years (OR=3.042; CI: 1.421-6.512; p=0.04) were identified as independent variables that significantly increased breast cancer risk of parous women. Compared to parous women who never practised breastfeeding, total breastfeeding time > 24 months decreased the risk of breast cancer (OR=0.258; CI: 0.084-0.787; p=0.017). The results indicated that modifiable reproductive factors contribute to breast cancer risk in women included in the present study. Women's knowledge about factors such as the protective effect of breastfeeding could reduce the risk of breast cancer.Rades, Dirk;Huttenlocher, Stefan;Dziggel, Liesa;Blanck, Oliver;Hornung, Dagmar;Mai, Khoa Trong;Ngo, Trang Thuy;Pham, Thai Van;Schild, Steven 2967
Many patients with few cerebral metastases receive radiosurgery alone. The goal of this study was to create a tool to estimate the survival of such patients. To identify characteristics associated with survival, nine variables including radiosurgery dose, age, gender, Eastern cooperative oncology group performance score (ECOG-PS), primary tumor type, number/size of cerebral metastases, location of cerebral metastases, extra-cerebral metastases and time between cancer diagnosis and radiosurgery were analyzed in 214 patients. On multivariate analysis, age (p=0.03), ECOG-PS (p=0.02) and extra-cerebral metastases (p<0.01) had significant impacts on survival. Scoring points for each patient were obtained from 12-month survival rates (in %) related to the significant variables divided by 10. Addition of the scoring points of the three variables resulted in a patient's total predictive score. Two groups were designed, A (10-14 points) and B (16-17 points). Twelve-month survival rates were 33% and 77%, respectively (p<0.001). Median survival times were 8 and 20 months, respectively. Because most patients of group A died from extra-cerebral disease and/or new cerebral lesions, early systemic treatment and additional WBI should be considered. As cause of death in group B was mostly new cerebral metastases, additional WBI appears even more important for this group.Gohari-Lasaki, Sahar;Gharesouran, Jalal;Ghojazadeh, Morteza;Montazeri, Vahid;Ardebili, Seiied Moitaba Mohaddes 2971
TP53 is assumed to be a very important tumour suppressor gene, as illustrated by recent reports that have shown effects of its polymorphisms on breast cancer risk. Arg72Pro and PIN3(16bp duplication) polymorphisms are proposed to have an effective role in structural changes of p53 and have therefore attracted interest as a risk factor for breast cancer in different populations. The aim of this study was to examine and determine whether p53 codon 72 and PIN3 Ins16 bp may be associated with an increased risk for breast cancer in female patients from the northwest of Iran. Genotyping was performed by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) method for a total of 100 women with breast cancer and 100 healthy women without any background of cancer, focusing on the TP53 Arg72Pro-16Del/Ins haplotypes and the combined genotypes. The results in this study established no statistical significant distinctions between the genotypes and a llele frequency were found for Arg72Pro and PIN3 Ins 16 bp polymorphisms between patients and controls.Qiu, Hui;Zhao, De-Ying;Yuan, Li-Mei;Zhang, Gong;Xie, Cong-Hua 2975
Background: Telomere length is closely associated with cellular radiosensitivity and WRAP53 is required for telomere addition by telomerase. In this research we assessed radiosensitivity of laryngeal squamous cell carcinoma Hep-2 cell lines after WRAP53 inhibition, and analyzed the molecular mechanisms. Materials and Methods: phWRAP53-siRNA and pNeg-siRNA were constructed and transfected into Hep-2 cells with lipofectamine. Expression of WRAP53 was analyzed by RT-PCR and Western-blottin, radiosensitivity of Hep-2 cells was assessed colony formation assay, and the relative length of telomeres was measured by QPCR. Results: The data revealed that the plasmid of phWRAP53-siRNA was constructed successfully, and the mRNA and protein levels of WRAP53 were both obviously reduced in the Hep-2 cell line transfected with phWRAP53-siRNA. After Hep-2 cells were irradiated with X-rays, the$D_0$ and$SF_2$ were 2.481 and 0.472, respectively, in the phWRAP53-siRNA group, much lower than in the control group ($D_0$ and$SF_2$ of 3.213 and 0.592) (P<0.01). The relative telomere length in the phWRAP53-siRNA group was$0.185{\pm}0.01$ , much lower than in the untreated group ($0.523{\pm}0.06$ ) and the control group ($0.435{\pm}0.01$ ). Conclusions: Decreasing the expression of WRAP53 using RNA interference technique can enhance the radiosensitivity of Hep-2 cell lines by influencing the telomere length. WRAP53 is expected to be a new target to regulate the radiosensitization of tumor cells.Zhang, Yuan-Yuan;Lu, Ling;Abliz, Guzalnur;Mijit, Fatima 2981
Background: Despite many epidemiological studies on the effects of dietary antioxidant micronutrients on risk of cervical cancer, the findings remain uncertain and little evidence is available for serum nutrient markers. The present study aimed to examine the relationship between serum carotenoid, retinol and tocopherol concentrations and risk of cervical cancer among Chinese women. Materials and Methods: We conducted a hospital-based case-control study in which 358 adults (158 incident cases and 200 controls) were recruited from Xinjiang, China. Serum levels of carotenoids (${\alpha}$ -carotene,${\beta}$ -carotene,${\beta}$ -cryptoxanthin, lycopene and lutein/zeaxanthin), retinol, and tocopherols (${\alpha}$ -tocopherol and${\gamma}$ -tocopherol) were assessed by reverse-phase high-performance liquid chromatography. Results: We found inverse associations between serum carotenoid (${\alpha}$ -carotene,${\beta}$ -carotene, and lutein/zeaxanthin) and tocopherol (${\alpha}$ -tocopherol) concentrations and the risk of cervical cancer after adjusting for potential confounders, but a null association for retinol. The ORs for 1-SD increase were 0.71 (95 % CI: 0.56-0.92; p=0.003) for total carotenoids and 0.75 (95 % CI: 0.60-0.94; p=0.008) for total tocopherols. Conclusions: These results show that higher serum concentrations of some carotenoids and tocopherols are associated with a lower risk of cervical cancer among Chinese women.Elsamany, Shereef Ahmed;Al-Fayea, Turki M;Alzahrani, Abdullah Said;Abozeed, Waleed Nabeel;Darwish, Waseem;Farooq, Mian Usman;Almadani, Ahmed Salahuddin;Bukhari, Esraa Ahmed 2987
Background: The prognostic role of thyroid transcription factor-1 (TTF-1) expression in lung cancer has been assessed but with inconsistent results. The present study aimed to evaluate the prognostic value of TTF1 expression in advanced non-squamous non-small cell lung cancer (NSCLC). Materials and Methods: In this retrospective study, patients with stage IIIB-IV non-squamous NSCLC were enrolled. Progression free survival (PFS) and overall survival (OS) were assessed according to TTF1 expression status, age categories (${\leq}60$ vs >60 years), gender, performance status (PS) (0-2 vs 3-4), type of 1st line chemotherapy (pemetrexed containing vs others) and EGFR status. Results: A total of 120 patients were included. In univariate analysis, PFS was improved in patients with PS 0-2 (7.0 vs 2.0 months, p=0.002) and those who received pemetrexed-containing chemotherapy (9.2 vs 5.8 months, p=0.004). OS was improved in female patients (23.0 vs 8.7 months, p<0.0001), PS 0-2 (14.4 vs 2.0 months, p<0.0001), those with pemetrexed-containing chemotherapy (17.0 vs 11.0 months, p=0.019), TTF1-positive (12.8 vs 5.8 months, p=0.011) and EGFR- mutant patients (23.0 vs 11.7 months, p=0.006). In multivariate analysis, male gender (HR=2.34, p=0.025) and non-pemetrexed containing therapy (HR=2.24, p=0.022) were independent predictors of worse PFS. Wild EGFR status (HR=2.49, p=0.015) and male gender (HR=2.78, p=0.008) were predictors of worse OS. Conclusions: Pemetrexed-containing therapy significantly improved PFS while OS was improved in EGFR mutant patients. Female patients had better PFS and OS. TTF1 expression was not a prognostic marker in advanced non-squamous NSCLC.Bhatti, Abu Bakar Hafeez;Waheed, Anum;Hafeez, Aqsa;Akbar, Ali;Syed, Aamir Ali;Khattak, Shahid;Kazmi, Ather Saeed 2993
Background: Distance from anal verge and abdominoperineal resection are risk factors for circumferential resection margin (CRM) positivity in rectal cancer. Induction chemotherapy (IC) before concurrent chemoradiation (CRT) has emerged as a new treatment modification. Impact of IC before concurrent CRT on CRM positivity in low rectal cancer remains to be independently studied. The objective of this study was to determine CRM positivity in low rectal cancer, with and without prior IC, and to identify predictors of disease free and overall survival. Materials and Methods: Patients who underwent surgery for rectal cancer between 2005 and 2011 were retrospectively reviewed and divided into two groups. Group 1 received IC before CRT and Group 2 did not. Demographics, clinicopathological variables and CRM status were compared. Actuarial 5 year disease free survival (DFS), overall survival (OS) and independent predictors of survival were determined. Results: Patients in the IC group presented with advanced stage (Stage 3=89.2% versus 75.4%) (P=0.02) but a high rate of total mesorectal excision (TME) (100% versus 93.4%) (P=0.01) and sphincter preservation surgery (54.9 % versus 22.9%) (P=0.001). Patients with low rectal cancer who received IC had a significantly low positive CRM rate (9.2% versus 34%) (P=0.002). Actuarial 5 year DFS in IC and no IC groups were 39% and 43% (P=0.9) and 5 year OS were 70% and 47% (P=0.003). Pathological tumor size [HR: 2.2, CI: 1.1-4.5, P=0.01] and nodal involvement [HR: 2, CI: 1.08-4, P=0.02] were independent predictors of relapse while pathological nodal involvement [HR: 2.6, CI: 1.3-4.9, P=0.003] and IC [HR: 0.7, CI: 0.5-0.9, P=0.02] were independent predictors of death. Conclusions: In low rectal cancer, induction chemotherapy before CRT may significantly decrease CRM positivity and improve 5 year overall survival.Buyukasik, Kenan;Sevinc, Mert Mahsuni;Gunduz, Umut Riza;Ari, Aziz;Gurbulak, Bunyamin;Toros, Ahmet Burak;Bektas, Hasan 2999
Background: This study aimed to evaluate upper gastrointestinal polyps detected during esophago-gastroduodenoscopy tests. Materials and Methods: We conducted a retrospective analysis on data regarding 55,987 upper gastrointestinal endoscopy tests performed at the endoscopy unit of Istanbul Education and Research Hospital between January 2006 and June 2012. Results: A total of 66 upper gastrointestinal polyps from 59 patients were analyzed. The most common clinical symptom was dyspepsia, observed in 41 cases (69.5%). The localizations of the polyps were as follows: 29 in the antrum (43.9%), 15 in the corpus (22.7%), 11 in the cardia (16.7%), 3 in the fundus (4.54%), 3 in the second portion of the duodenum (4.54%), 2 in the bulbus (3.03%) and 3 in the lower end of the esophagus (4.54%). Histopathological types of polyps included hyperplastic polyps (44) (66.7%), faveolar hyperplasia (8) (12.1%), fundic gland polyps (4) (6.06%), squamous cell polyps (4) (6.06%), hamartomatous polyps (3) (4.54%), and pyloric gland adenoma (3) (4.54%). Histopathological analysis of the gastric mucosa showed chronic atrophic gastritis in 30 cases (50.84%), HP infection in 33 cases (55.9%) and intestinal metaplasia in 19 cases (32.20%). In 3 cases with multiple polyps, adenocarcinoma was detected in hyperplastic polyps. Conclusions: Among polypoid lesions of the upper gastrointestinal tract, the most common histological type is hyperplastic polyps. Generally, HP infection is associated with chronic atrophic gastritis and intestinal metaplasia. The incidence of adenocarcinoma tends to be higher in patients with multiple hyperplastic polyps.Wang, Bi;Yu, Lei;Yang, Guo-Zhen;Luo, Xin;Huang, Lin 3003
Objective: To explore the application of multiplex nested methylated specific polymerase chain reaction (PCR) in the early diagnosis of epithelial ovarian carcinoma (EOC). Materials and Methods: Serum and fresh tissue samples were collected from 114 EOC patients. RUNX3, TFPI2 and OPCML served as target genes. Methylation levels of tissues were assessed by multiplex nested methylated specific PCR, the results being compared with those for carcinoma antigen 125 (CA125). Results: The serum free deoxyribose nucleic acid (DNA) methylation spectrum of EOC patients was completely contained in the DNA spectrum of cancer tissues, providing an accurate reflection of tumor DNA methylation conditions. Serum levels of CA125 and free DNA methylation in the EOC group were evidently higher than those in benign lesion and control groups (p<0.05). Patients with early EOC had markedly lower serum CA125 than those with advanced EOC (p<0.05), but there was no significant difference in free DNA methylation (p>0.05). The sensitivity, specificity and positive predicative value (PPV) of multiplex nested methylated specific PCR were significantly higher for detection of all patients and those with early EOC than those for CA125 (p<0.05). In the detection of patients with advanced EOC, the PPV of CA125 detection was obviously lower than that of multiplex nested methylated specific PCR (p>0.05), but there was no significant difference in sensitivity (p>0.05). Conclusions: Serum free DNA methylation can be used as a biological marker for EOC and multiplex nested methylated specific PCR should be considered for early diagnosis since it can accurately determine tumor methylation conditions.Sun, Shuang;Jin, Guo-Jiang;Zhao, Yan;Kang, Hui 3009
The epidermal growth factor (EGF) may play a pathological role in hepatocellular carcinoma (HCC). However, the conclusions of published reports on the relationship between the EGF$61^*A/G$ polymorphism and HCC risk remain controversial. To derive a more precise estimation we performed a meta-analysis based on 14 studies that together included 2,506 cases and 4,386 controls. PubMed, EMBASE, Web of Knowledge and the Chinese National Knowledge Infrastructure (CNKI) databases were used to retrieve articles up to August 1, 2014. The crude odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated to evaluate the association. Meta-analysis results showed a significant association between the EGF$61^*A/G$ polymorphism and HCC risk in all four genetic models (allele model: OR=1.25, 95%CI=1.12-1.40; dominant model: OR=1.32, 95%CI=1.14-1.54; recessive model: OR=1.33, 95%CI=1.12-1.58; ho-mozygous model: OR=1.59, 95%CI=1.33-1.90). Moreover, significant associations were observed when stratified by ethnicity, source of controls, etiology and genotype methods. Thus, this meta-analysis suggests that the G-allele of the EGF$61^*A/G$ polymorphism is associated with an increased risk of HCC, especially in Asians and Caucasians, without influence from the source of controls or etiological diversity. Further studies with larger population sizes are needed to confirm these results.Eker, Baki;Ozaslan, Ersin;Karaca, Halit;Berk, Veli;Bozkurt, Oktay;Inanc, Mevlude;Duran, Ayse Ocak;Ozkan, Metin 3015
Background: Colorectal cancer (CRC) is a major cause of mortality in developed countries, and it is the third most frequent malignancy in Turkey. There are many biological, genetic, molecular, and tissue-derived prognostic factors for CRCs. In this study, we evaluated prognostic factors in patients who were metastatic at diagnosis or progressed to metastatic disease during follow-up. Patients and Methods: This study included 116 patients with malignancies either in the colon or rectum. Of these, 65 had metastatic disease at diagnosis, and 51 progressed to metastatic disease during the course of the disease. The parameters evaluated were age, gender, comorbidity, performance status and stage of the disease at the beginning, localization, history of surgery, chemotherapy regimen, response to first-line treatment, K-RAS status, site and number of metastases, expression of tumor predictors (CEA, CA19-9), and survival times. A multivariate analysis conducted with factors that considered statistically significant in the univariate analysis. Findings: Median age was 56 (32-82) years and the male/female ratio was 80/36. Eleven patients were at stage II, 40 at stage III, and 65 at stage IV at diagnosis. Twenty three patients had tumor in the right colon, 48 in the left colon, and 45 in the rectum. Ninety seven patients were operated, and 27 had surgical metastasectomy. Ninety three patients received targeted therapy. At the end of follow-up, 61 patients had died, and 55 survived. Metastatic period survival times were longer in the adjuvant group, but the difference did not reach the level of statistical significance (adjuvant group: median 29 months, metastatic group: median 22 months; p=0.285). In the adjuvant group before the metastatic first-line therapy, CEA and CA 19-9 levels were significiantly lower compared to the metastatic group (p<0.005). We also found that patients with elevated tumor predictor (CEA, CA 19-9) levels before the first-line therapy had significiantly poorer prognosis and shorter survival time. Survival was significiantly better with the patients who were younger than 65 years of age, had better initial performance status, a history of primary surgery and metastatectomy, and single site of metastasis. Those who benefitted from the first-line therapy were K-RAS wild type and whose tumor markers (CEA, CA 19-9) were not elevated before the first line therapy. Conclusions: Among the patients with metastatic CRC, those who benefited from first-line therapy, had history of metastasectomy, were K-RAS wild type and had low CA 19-9 levels before the first-line therapy, showed better prognosis independent of other factors.Kekilli, Kezban Esra;Abakay, Candan Demioz;Tezcan, Gulcin;Tunca, Berrin;Egeli, Unal;Saraydaroglu, Ozlem;Esbah, Onur;Ekinci, Ahmet Siyar;Arslan, Sonay;Uslu, Nuri;Ozkan, Lutfi 3023
Purpose: To investigate the effects of epidermal growth factor receptor (EGFR), cytokeratin 19 (CK19), cytokeratin 20 (CK20) and survinin gene expression on local control (LC) and overall survival (OS) in patients with locally advanced head and neck cancer (LAHNC) who were administered radiotherapy (RT). Materials and Methods: Twenty-six patients who were admitted to Uludag University Medical Faculty Department of Radiation Oncology with a diagnosis of LAHNC (GIII-GIV) were included in this study. Gene expression was evaluated in tumor tissues and peripheral blood. RNA isolation was performed on paraffinized tumor tissues and peripheral blood samples obtained before RT (BR). The densities of the obtained RNAs were analyzed at 260/280 nm. cDNA samples obtained from total RNA,EGFR, CK19, CK20 and survinin gene expression levels were assessed via the Sybr Green method and data were analyzed with the${\Delta}{\Delta}Ct$ method. The same process was repeated for peripheral blood samples taken after RT (AR). Results: The female/male ratio was 3:23 and the mean age was 56.5 years (38-75years). After radiotherapy, CK19 and CK20 levels in the peripheral blood were found to be correlated according to Pearson correlation analysis(p=0.049). This result indicates a possibility of remaining positive for CK19 and CK20 in the peripheral blood even after RT in patients with CK19, CK20, and EGFR positive tumors before RT. There was a statistically significant correlation between survinin levels measured BR and AR (p=0.028). Conclusions: In this study, we found that patients with any EGFR, CK19, CK20 or survinin positivity in their peripheral blood obtain less benefit from radiotherapy. A wider patient population and advanced protein analyses are necessary in order to increase the reliability of our findings.Lee, Jungun;Lee, Dong-Ryul;Lee, Do-Hoon;Paek, Yu-Jin;Lee, Won-Chul 3029
Background: While the perinatal outcomes of active maternal smoking are well documented, results of the effects of environmental tobacco smoke (ETS) exposure during pregnancy are inconsistent. We aimed to examine the effect of ETS exposure, assessed by maternal hair nicotine levels at$35^{th}$ week of gestation, on birth weight and the risk of small for gestational age (SGA) and low birth weight (LBW). Materials and Methods: A total of 871 non-smoking healthy pregnant women were recruited by one Korean hospital between 1 October 2006 and 31 July 2007. Hair samples were collected and anthropometric questionnaires administered at$35^{th}$ week of gestation. The primary outcome was birth weight and secondary outcomes were the risk of babies being SGA and LBW. Results: Log-transformed hair nicotine concentrations were inversely related with birth weight after adjusting for confounding variables (${\beta}=-0.077$ , p=0.037). After stratifying hair nicotine levels by tertiles (T1, low [0.0-0.28 ng/mg]; T2, medium [0.29-0.62 ng/mg]; and T3, high [0.63-5.99 ng/mg]), the mean birth weight in each groups were 3,342g (T1) 3,296g (T2) and 3,290 g (T3), respectively. However the difference between groups was not statistically significant by analysis of co-variance (ANCOVA) adjusting for covariates (p=0.062). In logistic regression analysis, the risk of SGA was higher in the T3 (OR=1.59, 95%CI 1.05-2.42) than in the reference group (T1), after controlling for confounding variables. The risk of low birth weight (<2,500g, LBW) was not significantly higher (OR=1.44, 95%CI 0.95-2.19), but the risk of babies being below 3,000g birth weight was increased in the T3 group (OR=1.53, 95%CI 1.00-2.36) compared with that in the T1 group. Conclusions: Maternal ETS exposure during pregnancy was inversely related with birth weight. The risk of SGA increased in the highest ETS exposure group compared with in the low exposure group. To prevent ETS exposure during pregnancy, more comprehensive tobacco control policies are needed.Li, Qiong;Ren, Fu-Qiang;Yang, Chun-Lei;Zhou, Li-Ming;Liu, Yan-You;Xiao, Jing;Zhu, Ling;Wang, Zhen-Grong 3035
Background: Isorhamnetin (Iso), a novel and essential monomer derived from total flavones of Hippophae rhamnoides that has long been used as a traditional Chinese medicine for angina pectoris and acute myocardial infarction, has also shown a spectrum of antitumor activity. However, little is known about the mechanisms of action Iso on cancer cells. Objectives: To investigate the effects of Iso on A549 lung cancer cells and underlying mechanisms. Materials and Methods: A549 cells were treated with$10{\sim}320{\mu}g/ml$ Iso. Their morphological and cellular characteristics were assessed by light and electronic microscopy. Growth inhibition was analyzed by MTT, clonogenic and growth curve assays. Apoptotic characteristics of cells were determined by flow cytometry (FCM), DNA fragmentation, single cell gel electrophoresis (comet) assay, immunocytochemistry and terminal deoxynucleotidyl transferase nick end labeling (TUNEL). Tumor models were setup by transplanting Lewis lung carcinoma cells into C57BL/6 mice, and the weights and sizes of tumors were measured. Results: Iso markedly inhibited the growth of A549 cells with induction of apoptotic changes. Iso at$20{\mu}g/ml$ , could induce A549 cell apoptosis, up-regulate the expression of apoptosis genes Bax, Caspase-3 and P53, and down-regulate the expression of Bcl-2, cyclinD1 and PCNA protein. The tumors in tumor-bearing mice treated with Iso were significantly smaller than in the control group. The results of apoptosis-related genes, PCNA, cyclinD1 and other protein expression levels of transplanted Lewis cells were the same as those of A549 cells in vitro. Conclusions: Iso, a natural single compound isolated from total flavones, has antiproliferative activity against lung cancer in vitro and in vivo. Its mechanisms of action may involve apoptosis of cells induced by down-regulation of oncogenes and up-regulation of apoptotic genes.Thanee, Malinee;Loilome, Watcharin;Techasen, Anchalee;Namwat, Nisana;Boonmars, Thidarut;Pairojkul, Chawalit;Yongvanit, Puangrat 3043
The tumor microenvironment (TME) includes numerous non-neoplastic cells such as leukocytes and fibroblasts that surround the neoplasm and influence its growth. Tumor-associated macrophages (TAMs) and cancerassociated fibroblasts (CAFs) are documented as key players in facilitating cancer appearance and progression. Alteration of the macrophage (CD68, CD163) and fibroblast (${\alpha}-SMA$ , FSP-1) cells in Opisthorchis viverrini (Ov) -induced cholangiocarcinoma (CCA) was here assessed using liver tissues from an established hamster model and from 43 human cases using immunohistochemistry. We further investigated whether M2-activated TAMs influence CCA cell migration ability by wound healing assay and Western blot analysis. Macrophages and fibroblasts change their phenotypes to M2-TAMs (CD68+, CD163+) and CAFs (${\alpha}-SMA+$ , FSP-1+), respectively in the early stages of carcinogenesis. Interestingly, a high density of the M2-TAMs CCA in patients is significantly associated with the presence of extrahepatic metastases (p=0.021). Similarly, CD163+ CCA cells are correlated with metastases (p=0.002), and they may be representative of an epithelial-to-mesenchymal transition (EMT) with increased metastatic activity. We further showed that M2-TAM conditioned medium can induce CCA cell migration as well as increase N-cadherin expression (mesenchymal marker). The present work revealed that significant TME changes occur at an early stage of Ov-induced carcinogenesis and that M2-TAMs are key factors contributing to CCA metastasis, possibly via EMT processes.Kaminska-Winciorek, Grazyna;Gajda, Maksymilian;Wydmanski, Jerzy;Tukiendorf, Andrzej 3051
Background: Skin self-examination (SSE) may facilitate early diagnosis of melanoma at a potentially curable stage. Little data are available concerning the SSE frequency and knowledge about the symptoms of melanoma in non-patient populations. The aim of our study was to assess the performance of skin self-examination, recognition of potential melanoma symptoms as well as behavior related to sun exposure among web users in Poland. Materials and Methods: A cross-sectional study was conducted among readers of a scientific portal. Invited respondents were asked to complete an online questionnaire. Finally, statistical analysis was conducted on 4,919 surveys towards potential clinical signs of melanoma and SSE performance. Results: Approximately 60% of respondents had ever performed SSE in their life. Only 18.4 % declared performance on a regular, monthly, basis. Factors promoting this activity were established to be bigger place of residence, higher education and sensitive skin phototype, higher level of knowledge concerning melanoma, safe tanning rules and, especially, past surgical excision of naevi. Declared longer use of tanning beds was linked to understanding better the importance of clinical features of melanoma. Awareness of hazardous behavior during sunbathing is associated with the attempts to change them. Conclusions: Regular SSE is not a common practice, whilst the knowledge about the clinical features of melanoma is varied. Therefore, constant pressure should be put on promotion of regular skin self-examination and teaching its proper techniques, including familiarity with the ABCD (asymmetry; border; color; diameter) rule and its extension of "EFG" (elevated, firm, progressive growth) criteria.Ugurluoglu, Ceyhan;Kurtipek, Ercan;Unlu, Yasar;Esme, Hidir;Duzgun, Nuri 3057
Background: Cytological examination of pleural effusions is very important in the diagnosis of malignant lesions. Thoracentesis is the first investigation to be performed in a patient with pleural effusion. In this study, we aimed to compare traditional with cell block methods for diagnosis of lung disease accompanied by pleural effusion. Materials and Methods: A total of 194 patients with exudative pleural effusions were included. Ten mililiters of fresh pleural fluid were obtained by thoracentesis from all patients in the initial evaluation. The samples gathered were divided to two equal parts, one for conventional cytological analysis and the other for analysis with the cell block technique. In cytology, using conventional diagnostic criteria cases were divided into 3 categories, benign, malignant and undetermined. The cell block sections were evaluated for the presence of single tumor cells, papillary or acinar patterns and staining with mucicarmine. In the cell block examination, in cases with sufficient cell counts histopathological diagnosis was performed. Results: Of the total undergoing conventional cytological analyses, 154 (79.4%)were reported as benign, 33 (17%) as malignant and 7 (3.6%) as suspicious of malignancy. With the cell block method the results were 147 (75.8%) benign, 12 (6.2%) metastatic, 4 (2.1%) squamous cell carcinoma, 18 (9.3%) adenocarcinoma, 5 (2.6%) large cell carcinoma, 2 (1%) mesothelioma, 3 (1.5%) small cell carcinoma, and 3 (1.5%) lymphoma. Conclusions: Our study confirmed that the cell block method increases the diagnostic yield with exudative pleural effusions accompanying lung cancer.Liu, Tie-Qin;Wang, Ge-Bang;Li, Zheng-Jun;Tong, Xiang-Dong;Liu, Hong-Xu 3061
Background: Rac3, a member of the Rac family of small guanosine triphosphatases (GTPases), regulates a variety of cell functions, including the organization of the cytoskeleton, cell migration, and invasion. Overexpression of Rac3 has been reported in several human cancers. However, the role of Rac3 in lung cancer (LC) has not been determined in detail. The purpose of this study was to investigate the effect of silencing of Rac3 expression in human LC cells and the consequences for cell survival. Materials and Methods: Lentivirus small hairpin RNA (shRNA) interference techniques were utilized to knock down the Rac3 gene. Gene and protein expression was quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. LC cell apoptosis was examined by annexin V-APC /propidium iodide staining. Results: Efficient silencing of Rac3 strongly inhibited A549 cell proliferation and colony formation ability, and significantly decreased tumor growth. Moreover, flow cytometry analysis showed that knockdown of Rac3 led to G2/M phase cell cycle arrest as well as an excess accumulation of cells in the G1 and S phase. Conclusions: Thus, functional analysis using shRNAs revealed a critical role for Rac3 in the tumor growth of LC cells. shRNA silencing of Rac3 could provide an effective strategy to treat LC.Muhamad, Nor Asiah;Kamaluddin, Muhammad Amir;Adon, Mohd Yusoff;Noh, Mohamed Asyraf;Bakhtiar, Mohammed Faizal;Tamim, Nor Saleha Ibrahim;Mahmud, Siti Haniza;Aris, Tahir 3067
Cervical cancer is the most common malignant cancer of the female reproductive organs worldwide. Currently, cervical cancer can be prevented by vaccination and detected at an early stage via various screening methods. Malaysia, as a developing country faces a heavy disease burden of cervical cancer as it is the second most common cancer among Malaysian women. This population based study was carried out to fulfil the primary aim of determining the survival rates of Malaysian women with cervical cancer and associated factors. Data were obtained from two different sources namely, the Malaysian National Cancer Registry (MNCR) and National Health Informatics Centre (NHIC) from 1st January 2000 to 31st December 2005. Kaplan Meier analyses were conducted to identify the overall survival rates and median survival time. Differences in survival among different ethnic and age group were compared using the log-rank test. A total of 5,859 patients were included. The median survival time for cervical cancer in this study was 65.8 months and the 5-year survival rate was 71.1%. The overall observed survival rates at 1, 3 and 5 years were 94.1%, 79.3% and 71.1% respectively. The log-rank test finding also showed that there were significant differences in the 5-year survival rate among different ethnic groups. Malays had the lowest survival rate of 59.2% followed by Indians (69.5%) and Chinese (73.8%). The overall 5-year survival rate among patients with cervical cancer in Malaysia is relatively good. Age and ethnic groups remain as significant determining factors for cervical cancer survival rate.Dehghan, Roghayeh;Feizi, Mohammad Ali Hosseinpour;Pouladi, Nasser;Adampourezare, Mina;Farajzadeh, Davoud 3073
Background: TP53 mutations are the most common genetic alterations in human cancers. There are also several polymorphisms in both exons and introns of TP53 that may influence its anti-tumor functions and increase the risk of cancer development. Associations of the TP53 intron 6 G13964C polymorphism with increased risk of development of several cancers have been investigated in numerous studies, but the results were controversial and conflicting. In this study, we aimed to investigate the probable association of this polymorphism with risk of both thyroid and breast cancers among the Iranian-Azeri population. Materials and Methods: We performed two separate case control studies on associations of the intron 6 polymorphism with two different kinds of cancer. In one case-control study, a total of 75 patients with thyroid carcinoma and 180 controls were analyzed and the other study included 170 patients with breast cancer and 135 healthy women. The intron 6 genotype was determined by RFLP-PCR and the SPSS 16 program was applied for data analysis. Results: For thyroid cancer, the frequencies of GG genotype were 96.0% in patients and 93.3% in controls. The GC genotype had a frequency of 4.0 % in patients and 6.7% in controls. In the study on breast cancer, the frequency of GG and GC genotypes in patients were 95.3% and 4.7%, respectively. In breast related control group, the frequency of GG genotype was 93.3 % and the frequency of GC genotype was 6.7%. None of the cases and controls had the CC genotype. Conclusions: There was no significant association between the TP53 intron 6 G13964C polymorphism and risk of development of both thyroid and breast cancer in Iranian-Azeri patients.Cancer-testis antigens (CTAs) are a group of tumor associated antigens with a restricted expression pattern in normal gametogenic tissues but expression in a broad range of malignancies. Their expression pattern has made them potential targets for immunotherapy. However, expression of some of these antigens has been demonstrated in normal stem cells as well as cancer stem cells (CSCs). As CSCs have been shown to be sources of metastasis and tumor recurrence, novel therapies are being focused on their eradication. On the other hand, CTA expression in normal stem cells raises the possibility that CTA based immunotherapies cause side effects in normal tissues.