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.
KSCI제15권8호
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Chemoprevention is an attempt to use nontoxic natural and synthetic substances or their mixtures to intervene the relatively early stages of carcinogenesis, before invasive characteristics are manifested. The consumption of fruits is well known to reduce the risk of human cancers. Although most fruits are available only on a seasonal basis, recent advances in food processing technologies have made it possible to extend the shelf life of fruits and fruit-products. Fruits can be preserved by applying different drying processes to reduce the moisture content. Different varieties of dried fruits are now sold in supermarkets, thereby making them readily accessible to consumers. Since oxidative stress and chronic inflammation play important roles in cancer development, dried fruits with antioxidative and anti-inflammatory properties hold promise for cancer chemoprevention. The antioxidant, anti-inflammatory and chemopreventive activities of dried fruits are largely attributed to their polyphenols and vitamins. Dried fruits contain adequate amounts of bioactive principles, such as anthocyanins, acetogenins, catechins, coumarins, phenolic acids, terpenes, xanthones, and others. Since numerous health beneficial phytochemicals in fruits are conserved even after processing, regular intake of dried fruits can help prevent cancer. This review addresses the chemopreventive potential of representative dried fruits and their active constituents.
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Majeed, Wafa;Aslam, Bilal;Javed, Ijaz;Khaliq, Tanweer;Muhammad, Faqir;Ali, Asghar;Raza, Ahmad 3353
Breast cancer is the most common in women worldwide, with some 5-10% of all cases due to inherited mutations of BRCA1 and BRCA2 genes. Obesity, hormone therapy and use of alcohol are possible causes and over-expression of leptin in adipose tissue may also play a role. Normally surgery, radiation therapy and chemotherapy allow a good prognosis where screening measures are in place. New hope in treatment measures include adjuvant therapy, neoadjuvant therapy, and introduction of mono-clonal antibodies and enzyme inhibitors. -
Attar, Rukset;Gasparri, Maria Luisa;Di Donato, Violante;Yaylim, Ilhan;Halim, Talha Abdul;Zaman, Farrukh;Farooqi, Ammad Ahmad 3359
Increasing attention is being devoted to the mechanisms by which cells receive signals and then translate these into decisions for growth, death, or migration. Recent findings have presented significant breakthroughs in developing a deeper understanding of the activation or repression of target genes and proteins in response to various stimuli and of how they are assembled during signal transduction in cancer cells. Detailed mechanistic insights have unveiled new maps of linear and integrated signal transduction cascades, but the multifaceted nature of the pathways remains unclear. Although new layers of information are being added regarding mechanisms underlying ovarian cancer and how polymorphisms in VDR gene influence its development, the findings of this research must be sequentially collected and re-interpreted. We divide this multi-component review into different segments: how vitamin D modulates molecular network in ovarian cancer cells, how ovarian cancer is controlled by tumor suppressors and oncogenic miRNAs and finally how vitamin D signaling regulates miRNA expression. Intra/inter-population variability is insufficiently studied and a better understanding of genetics of population will be helpful in getting a step closer to personalized medicine. -
Zhao, Song-Feng;Zhang, Xiao;Zhang, Xiao-Jian;Shi, Xiu-Qin;Yu, Zu-Jiang;Kan, Quan-Cheng 3363
Background: Curcumin, a phenolic compound extracted from the rhizomes of Curcuma longa, has shown cytotoxic effects against a variety of cancers. The aim of this study was to identify potential microRNA (miRNA) mediators of the anticancer effects of curcumin in ovarian cancer cells. Materials and Methods: SKOV3 ovarian cancer cells were treated with curcumin ($10-60{\mu}M$ ) and miR-9 expression, cell proliferation, and apoptosis were assessed. The effects of miR-9 depletion on curcumin-mediated growth suppression were also examined. Phosphorylation of Akt and forkhead box protein O1 (FOXO1) was measured in cells with miR-9 overexpression or curcumin treatment. Results: Curcumin caused a significant and dose-dependent increase of miR-9 expression in SKOV3 cells, while significantly impeding cell proliferation and stimulating apoptosis. Depletion of miR-9 significantly (p<0.05) attenuated the growth-suppressive effects of curcumin on SKOV3 cells, coupled with reduced percentages of apoptotic cells. In contrast, overexpression of miR-9 significantly enhanced the cleavage of caspase-3 and poly(ADP-ribose) polymerase and promoted apoptotic death in SKOV3 cells. Western blot analysis showed that both miR-9 overexpression and curcumin similarly caused a significant (p<0.05) decline in the phosphorylation of Akt and FOXO1, compared to untreated cells. Conclusions: The present study provided evidence that curcumin exerts its cytotoxic effects against SKOV3 ovarian cancer cells largely through upregulation of miR-9 and subsequent modulation of Akt/FOXO1 axis. Further studies are needed to identify direct targets of miR-9 that mediate the anticancer effects of curcumin in ovarian cancer cells. -
Dai, Jin;Tang, Kun;Xiao, Wei;Yu, Gan;Zeng, Jin;Li, Wei;Zhang, Ya-Qun;Xu, Hua;Chen, Zhi-Qiang;Ye, Zhang-Qun 3369
Background: C-reactive protein (CRP), considered as a prototypical inflammatory cytokine, has been proposed to be involved in tumor progression through inflammation. Recent studies have indicated CRP as a progostic predictor for urological cancers, but the results remain controversial. Materials and Methods: A systematic search of Medline, Scopus and the Cochrane Library was performed to identify eligible studies published between Jan 1, 2001 and Sep 1, 2013. Outcomes of interest were collected from studies comparing overall survival (OS), cancer-specific survival (CSS) and relapse-free survival (RFS) in patients with elevated CRP levels and those having lower levels. Studies were pooled, and combined hazard ratio (HR) of CRP with its 95% confidence interval (CI) for survival were used for the effect size estimate. Results: A total of 43 studies (7,490 patients) were included in this meta-analysis (25 for RCC, 10 for UC, and 8 for PC). Our pooled results showed that elevated serum CRP level was associated with poor OS (HR: 1.26, 95%CI: 1.22-1.30) and RFS (HR: 1.38 95%CI: 1.29-1.47), respectively. For CSS the pooled HR (HR: 1.33, 95%CI: 1.28-1.39) for higher CRP expression could strongly predict poorer survival in urological cancers. Simultaneously, elevated serum CRP was also significantly associated with poor prognosis in the subgroup analysis. Conclusions: Our pooled results demonstrate that a high serum level of CRP as an inflammation biomarker denotes a poor prognosis of patients with urological cancers. Further large prospective studies should be performed to confirm whether CRP, as a biomarker of inflammation, has a prognostic role in urological cancer progression. -
Akinci, Muhammed Bulent;Sendur, Mehmet Ali Nahit;Aksoy, Sercan;Yazici, Ozan;Ozdemir, Nuriye Yildirim;Kos, Tugba;Yaman, Sebnem;Altundag, Kadri;Zengin, Nurullah 3377
Background: The incidence of colorectal cancer increases with vitamin D deficiency as shown in recently published studies. In addition, prospective investigations have indicated that low vitamin D levels may be associated with increased mortality of colorectal cancer, especially in stage III and IV cases. However, the exact incidence of vitamin D deficiency and the relation between vitamin D deficiency and osteopenia/osteporosis is still not known. The aim of this study is to identify severity of vitamin D deficiency and absolute risk factors of osteopenia/osteoporosis in colorectal cancer survivors. Materials and Methods: A total of 113 colorectal cancer survivors treated with surgery and/or chemotherapy${\pm}$ radiotherapy were recruited from medical oncology outpatient clinics during routine follow-up visits in 2012-2013. Bone mineral densitometry (BMD) was performed, and serum 25-OH vitamin D levels were also checked on the same day of the questionnaire. The patients was divided into 2 groups, group A with normal BMD and group B with osteopenia/osteoporosis. Results: The median age of the study population was 58 (40-76). Thirty (30.0%) were female, whereas 79 (70.0%) were male. The median follow-up was 48 months (14-120 months). Vitamin D deficiency was found in 109 (96.5%); mild deficiency (20-30 ng/ml) in 19 (16.8%), moderate deficiency (10-20 ng/ml) in 54 (47.8%) and severe deficiency (<10 ng/ml) in 36 (31.9%). Osteopenia was evident in 58 (51.4%) patients whereas osteoporosis was noted in 17 (15.0%). Normal BMD was observed in 38 (33.6%). No apparent effects of type of surgery, presence of stoma, chemotherapy, radiotherapy and TNM stage were found regarding the risk of osteopenia and osteoporosis. Also, the severity of the vitamin D deficiency had no effect in the risk of osteopenia and osteporosis (p=0.93). In female patients, osteopenia/osteoporosis were observed in 79.5% patients as compared to 60.7% of male patients (p=0.04). Conclusions: In our study, vitamin D deficiency and osteopenia/osteoporosis was observed in 96.5% and 66.4% of colorectal cancer survivors, respectively. There is no defined absolute risk factor of osteopenia and osteoporosis in colorectal cancer survivors. To our knowledge, in the literature, our study is the first to evaluateall the risk factors of osteopenia and osteoporosis in colorectal cancer survivors. -
Shin, Sangjin;Kim, Youn Hee;Hwang, Jin Sub;Lee, Yoon Jae;Lee, Sang Moo;Ahn, Jeonghoon 3383
Background: Prostate cancer is rapidly increasing in Korea and professional societies have requested adding prostate specific antigen (PSA) testing to the National Cancer Screening Program (NCSP), but this started a controversy in Korea and neutral evidence on this issue is required more than ever. The purpose of this study was to provide economic evidence to the decision makers of the NCSP. Materials and Methods: A cost-utility analysis was performed on the adoption of PSA screening program among men aged 50-74-years in Korea from the healthcare system perspective. Several data sources were used for the cost-utility analysis, including general health screening data, the Korea Central Cancer Registry, national insurance claims data, and cause of mortality from the National Statistical Office. To solicit the utility index of prostate cancer, a face-to-face interview for typical men aged 40 to 69 was conducted using a Time-Trade Off method. Results: As a result, the increase of effectiveness was estimated to be very low, when adopting PSA screening, and the incremental cost effectiveness ratio (ICER) was analyzed as about 94 million KRW. Sensitivity analyses were performed on the incidence rate, screening rate, cancer stage distribution, utility index, and treatment costs but the results were consistent with the base analysis. Conclusions: Under Korean circumstances with a relatively low incidence rate of prostate cancer, PSA screening is not cost-effective. Therefore, we conclude that adopting national prostate cancer screening would not be beneficial until further evidence is provided in the future. -
Background: Vitamin D has been suggested as one of the critical factors for female reproductive health with protective activities against different cancers but there are conflicting facts regarding its role on breast cancer without any clear data on premenopausal cases. This study aimed to evaluate the role of vitamin D from dietary sources and sunlight exposure on the incidence of premenopausal breast cancer. Materials and Methods: We conducted a case control study on 60 newly diagnosed premenopausal breast cancer patients and 116 normal women who lived in Sabzevar and surrounding villages in Razavi, Khorasan, a rural and conservative area of Iran. Results: The mean concentrations of 25-OH vitamin D in cases and controls were
$15.2{\pm}8.15$ vs$15.5{\pm}7/45ng/ml$ , both well below normal values elsewhere. In fact 50% of analyzed individuals showed very severe or severe vitamin D deficiency and the rest (25%) were detected in suboptimal levels. Although the lack of vitamin D and calcium supplementation increased slightly the risk of premenopausal breast cancer (p=0.009, OR=1.115, CI 95%=1.049-1.187), higher prevalence of weekly egg consumption (86.66% vs 96.55%, p=0.023, OR=0.232, CI 95% 0.065-0.806) showed a slight protective role. The last but the most important risk factor was lack of sunlight exposure because the breast cancer patients had total body coverage from sun (p=0.007, OR=10.131, CI 98% 0.314-78.102). Conclusion: This study pointed out the role of vitamin D and other possible risk factors on the development and growth of breast tumors in this special geographical region. Although this study has revealed the interactions between hormonal and environmental factors in this province of Iran, understanding the deficiency pattern and its contribution to other lifestyle factors elsewhere is also necessary. -
Wang, Xue-Jian;Zhang, Xiu-Rong;Zhang, Lei;Li, Qing-Hua;Wang, Lin;Shi, Li-Hong;Fang, Chun-Yan 3397
Determining cell quantity is a common problem in cytology research and anti-tumor drug development. A simple and low-cost method was developed to determine monolayer and adherent-growth cell quantities. The cell nucleus is located in the cytoplasm, and is independent. Thus, the nucleus cannot make contact even if the cell density is heavy. This phenomenon is the foundation of accurate cell-nucleus recognition. The cell nucleus is easily recognizable in images after fluorescent staining because it is independent. A one-to-one relationship exists between the nucleus and the cell; therefore, this method can be used to determine the quantity of proliferating cells. Results indicated that the activity of the histone deacetylase inhibitor Z1 was effective after this method was used. The nude-mouse xenograft model also revealed the potent anti-tumor activity of Z1. This research presents a new anti-tumor-drug evaluation method. -
Liu, Yang;Fan, Wei;Chen, Hao;Yu, Ming-Xia 3403
Context: Interest exits in whether TNF-alpha antagonists increase the risk of breast cancer and total malignancies in patients with rheumatoid arthritis (RA). Objectives: To analyze the risk of malignancies, especially breast cancer, in patients with RA enrolled in randomized control trials (RCTs). Methods: A systematic literature search for RCTs from 1 January 1998 to 1 July 2013 from online databases, such as PubMed, WILEY, EMBASE, ISI web of knowledge and Cochrane Library was conducted. Studies included RCTs that compared the safety of at least one dose of the five TNF-${\alpha}$ antagonists with placebo or methotrexate (MTX) (or TNF-${\alpha}$ antagonists plus MTX vs placebo plus MTX) in RA patients for more than 24 weeks and imported all the references into document management software EndNote${\times}6$ . Two independent reviewers selected studies and extracted the data about study design, patients' characteristics and the type, number of all malignancies. Results: 28 RCTs from 34 records with 11,741 patients were analyzed. Of the total, 97 developed at least one malignancy during the double-blind trials, and breast cancer was observed in 17 patients (17.5% of total malignancies). However, there was no statistically significant increased risk observed in either the per protocol (PP) model (OR 0.65, 95%CI [0.22, 1.93]) or the modified intention to treat (mITT) model (OR 0.75, 95%CI [0.25, 2.21]). There were also no significant trend for increased risk of total malignancies on anti-TNF-${\alpha}$ therapy administered at approved doses in either model (OR, 1.06, 95%CI [0.64, 1.75], and OR, 1.30, 95%CI [0.80, 2.14], respectively). As to the two models, modified intention to treat model analysis led to higher estimation than per protocol model analysis. Conclusions: This study did not find a significantly increased risk of breast cancer and total malignancies in adults RA patients treated with TNF-${\alpha}$ antagonists at approved doses. However, it cannot be ignored that more patients developed malignancies with TNF-${\alpha}$ antagonists therapy compared with patients with placebo or MTX, in spite of the lack of statistical significance, so that more strict clinical trials and long-term follow-up are needed, and both mITT and PP analyses should be used in such safety analyses. -
Almobarak, Ahmed Omer;Elhassan, Taiseer Mohamed;Elhoweris, Mohamed Hassan;Awadalla, Heitham Mohammed;Elmadhoun, Wadie Mohamed Yasin;Ahmed, Mohamed Hassan 3411
Background: Cytology for breast lesions is a safe, rapid and cost-effective with a high specificity and sensitivity. Objective: To determine the cytomorphologic patterns of breast lesions identified among a group of Sudanese patients. Materials and Methods: This study included 759 patients undergoing either a fine needle aspiration FNA, nipple discharge (ND) smears or breast skin scraping (SS) at a cytology clinic in Khartoum. Clinical and demographic data were reviewed. Stained smears were categorized into: inadequate sample, normal breast, benign lesion, suspicious, or malignant neoplasm. Results: Of the 759 cases, 734 (96.71%) were FNA, 18 (2.37%) ND and 7 cases (0.92%) SS. For 28 cases, FNA was done under ultrasound guidance. Females were 720 (94.86%). Benign lesions were 423 (55.75%) and 248 (32.67%) were malignant and 77 (10.14%) of smears were normal without any detected abnormality. Ten (1.31%) cases were suspicious for malignancy, and only one case (0.13%) was reported as inadequate. Most lesions were observed among the age group 30 years and above. Conclusions: Most patients investigated have benign lesions, one third of cytological smears were malignant. FNAC is a useful tool for investigating breast lesions in limited-resource settings. -
Suren, Dinc;Yildirim, Mustafa;Alikanoglu, Arsenal Sezgin;Kaya, Vildan;Yildiz, Mustafa;Dilli, Utku Donem;Sezer, Cem 3415
Background: AKAP12 inhibits oncogenic proliferation, invasion, chemotaxis and neovascularization. Bcl-2 and p53 are two important apoptotic markers that play roles in apoptotic processes. It has been found that AKAP12 blocks the cell cycle and induces apoptosis in fibrosarcoma cells. In our study we assessed the relationship of AKAP12 with apoptotic markers, Bcl-2 and p53. Materials and Methods: Our study included 45 cases that were histopathologically diagnosed with colorectal carcinoma from the tissue samples acquired by surgical resection. AKAP 12, Bcl-2, and p53 expression was examined by immunohistochemistry. Results: A total of 45 colorectal adenocarcinoma patients - 17 (37.8%) females and 28 (62.2%) males - were included in this study. AKAP12 expression was found to be negative in 8 patients (17.8%), and positive in 37 patients (82.2%). Bcl-2 was found positive in 6 patients (13.3%) and p53 in 29 patients (55.6%). AKAP12 expression had no significant relation with Bcl-2 and p53 expression (p:0.939, p:0.079, respectively). Conclusions: Although various studies have pointed to apoptotic activity of AKAP12, the literature is limited regarding relations with p53 or Bcl-2 expression. In the present study, we found no relation in colorectal carcinomas. -
Di, Bao-Shan;Wei, Kong-Ping;Tian, Jin-Hui;Xiao, Xiao-Juan;Li, Yan;Zhang, Xu-Hui;Yu, Qin;Yang, Ke-Hu;Ge, Long;Huang, Wen-Hui;Zhang, Fang-Wa 3419
Background: Our aim was to conduct a meta-analysis to compare the efficacy and safety of pemetrexed and docetaxel for non-small cell lung cancer (NSCLC). Materials and Methods: We systematically searched the Cochrane Library, PubMed, Embase, China Biology Medicine Database for randomized controlled trials (RCTs) comparing the efficacy and toxicities of pemetrexed versus docetaxel as a treatment for advanced NSCLC. We limited the languages to English and Chinese. Two reviewers independently screened articles to identify eligible trials according to the inclusion and exclusion criteria and assessed the methodological quality of included trials, and then extracted data. The meta-analysis was performed using STATA12.0. Results: Six RCTs involving 1,414 patients were identified. We found that there was no statistically significant differences in overall response rate, survival time, progression-free survival, disease control rate, and 1-2yr survival rate (p>0.050) but it is worthy of mention that patients in the pemetrexed arms had significantly higher 3-yr survival rate (P=0.002). With regard to the grade 3 or 4 hematological toxicity, compared with docetaxel, pemetrexed led to lower rate of grade 3-4 febrile neutropenia, neutropenia, and leukocyts toxicity (p<0.001). There was no significant difference in anemia between the two arms (p=0.08). In addition, pemetrexed led to higher rate of grade 3-4 thrombocytopenia toxicity (p=0.03). As for the non-hematological toxicities, compared with docetaxel, pemetrexed group had lower rate of grade 3-4 diarrhea and alopecia. Conclusions: Pemetrexed was almost as effective as docetaxel in patients with advanced NSCLC. At the same time, pemetrexed might increase the 3-yr survival rate. As for safety, pemetrexed led to lower rate of grade 3-4 febrile neutropenia, neutropenia, leukocytes, diarrhea and alopecia toxicity. However, it was associated with a higher rate of grade 3-4 thrombocytopenia. -
Li, Xiao-Li;Zhou, Fa-Ming;Shangguan, Shou-Qin;Zou, Wen-Qin;Deng, Yan-Qing;Chen, Tao;Chen, Guang-Hui 3425
Objective: To explore the value of computed tomography (CT) in the differential diagnosis of glioma stroke and simple cerebral hemorrhage. Materials and Methods: A total of 45 patients with glioma stroke and stroke as the initial symptom in our hospital from Jun., 2009 to Oct., 2013 were selected along with 50 individuals with simple cerebral hemorrhage in the same period randomly collected as a control group. The CT results in both groups were analyzed and compared. Results: In the observation group, there were 25 patients with astrocytoma (55.6%), 11 with oligodendroglioma (24.4%), 8 with ependymoma (17.2%) and 1 with glioblastoma multiforma (GBM, 2.22%). Additionally, the major CT manifestation was coexistence of hemorrhage and tumor signs. By comparison, it could be found that the proportions of patients respectively with peripheral edema and space-occupying effect in the observation group were significantly higher than in the control group (P<0.01). Conclusions: Application of CT examination combined with medical history in patients has very important clinical value in the differential diagnosis of glioma stroke and simple cerebral hemorrhage. -
Effect of Perceived Social Support on Psychosocial Adjustment of Turkish Patients with Breast CancerRizalar, Selda;Ozbas, Ayfer;Akyolcu, Neriman;Gungor, Bulent 3429
Aims: To identify the psychosocial adjustment of Turkish patients with breast cancer and the effects of perceived social support on their adjustment. Materials and Methods: The sample comprised 100 volunteering patients diagnosed with breast cancer in the last six months reporting to the Outpatient Chemotherapy Unit at the Medical Faculty Hospital in northern Turkey. The data for the study were collected through the Descriptive Information Form, the Psychosocial Adjustment to Illness Scale-Self-reflection (PAIS-SR) and the Cancer-Specific Social Support Scale and analyzed via SPSS 16.0 for Windows. Descriptive statistics, Chi square test, ANOVA and correlation were used to evaluate data. Results: There was a negative significant correlation between mean scores in the sub-scales of the social support scale and the ones in the sub-scales of the psychosocial adjustment to illness scale (p<0.05). Similarly, there was a negative significant correlation between confidence support and health care orientation as well as adjustment to social environment. Likewise, emotional support was in a negative significant correlation with health care orientation, adjustment to domestic environment, extended family relationships and adjustment to social environment. Conclusions: It was concluded that social support for patients with breast cancer had an influence on their psychosocial adjustment to illness. Holistic care should be given to breast cancer patients by oncology nurses especially in the first six months of treatment. It could be concluded that patients should be accompanied by their family/relatives in treatment and care following their diagnosis with breast cancer, that their family should be made more aware of the fact that the patient should be physically and psychologically supported, that patients with breast cancer should be provided with domiciliary care, and that they should be encouraged to participate in social support groups. -
Zeichner, Simon Blechman;Cavalcante, Ludimila;Suciu, Gabriel Pius;Ruiz, Ana Lourdes;Hirzel, Alicia;Krill-Jackson, Elisa 3435
Background: Axillary lymph node status at diagnosis remains the strongest predictor of long-term survival in breast cancer. Patients with more than ten axillary lymph nodes at diagnosis have a poor long-term survival. In this single institutional study, we set out to evaluate the prognosis of this high-risk group in the era of multimodality therapy. Materials and Methods: In this retrospective study, we looked at all breast cancer patients with greater than ten axillary lymph nodes diagnosed at Mount Sinai Medical Center (MSMC) from January 1st 1990 to December 31st 2007 (n=161). In the univariate analysis, descriptive frequencies, median survival, and 5- and 10-year survival rates were estimated for common prognostic factors. A multivariate prognostic analysis for time-to-event data, using the extended Cox regression model was carried out. Results: With a median and mean follow-up of 70 and 89.9 months, respectively, the overall median survival was estimated to be 99 months. The five-year disease-free survival (DFS) was 59.3% and the ten-year DFS was 37.9%, whereas the five- and ten-year overall survival (OS) was 66.6% and 43.9%, respectively. Multivariate analysis revealed a significant improvement in DFS among black patients compared to whites (p=0.05), improved DFS and OS among young patients (ages 21-45) compared to elderly patients (age greater than 70) (p=0.00176, p=0.0034, respectively), and improved DFS and OS among patients whose tumors were ER positive (p=0.049, p=0.0034). Conclusions: In this single institution study of patients with greater than 10 positive axillary nodes, black patients had a significantly improved DFS compared with white patients. Young age and ER tumor positivity was associated with improved outcomes. Using multivariate analysis, there were no other variables associated with statistically significant improvements in DFS or OS including date of diagnosis. Further work is needed to improve breast cancer survival in this subgroup of patients. -
Kwon, Whi-An;Oh, Tae Hoon;Lee, Jae Whan;Park, Seung Chol 3443
The aim of this study was to determine predictive factors for neutropenia after docetaxel-based systemic chemotherapy in patients with castration-resistant prostate cancer (CRPC). The study included 40 Korean CRPC patients who were treated with several cycles of docetaxel plus prednisolone from May 2005 to May 2012. Patients were evaluated for neutropenia risk factors and for the incidence of neutropenia. In this study, nine out of forty patients (22.5%) developed neutropenia during the first cycle of docetaxel-based systemic chemotherapy. Four experienced grade 2, three grade 3, and one grade 4 neutropenia. Multivariate analysis showed that pretreatment white blood cell (WBC) count (p=0.042), pretreatment neutrophil count (p=0.015), pretreatment serum creatinine level (p=0.027), and pretreatment serum albumin level (p=0.017) were significant predictive factors for neutropenia. In conclusion, pretreatment WBC counts, neutrophil counts, serum creatinine levels, and serum albumin levels proved to be significant independent risk factors for the development of neutropenia induced by docetaxel-based systemic chemotherapy in patients with CRPC. -
Zhang, Yu-Mei;Li, Yong-Qiang;Liu, Zhi-Hui;Liao, Xiao-Li;Liang, Rong;Lin, Yan;Yuan, Chun-Ling;Liao, Si-Na;Liang, Chao-Yong;Li, Qian;Li, Le-Qun 3447
Objective: To observe the clinical efficacy of bevacizumab concomitant with pemetrexed in patients with advanced non-small cell lung cancer (NSCLC). Materials and Methods: A total of 72 patients were randomly divided into a combination group (pemetrexed+bevacizumab, n=36) and a pemetrexed group (n=36) and assessed for disease control (CR+PR+SD) after 4-cycles of first-line GP chemotherapy (gemcitabine+cisplatin). Clinical efficacy, progression-free survival time (PFS), overall survival time (OS), overall response rate (ORR), disease control rate (DCR) and rate of adverse responses between two groups were observed and compared. Results: ORR and DCR were 27.8% and 83.4% in combination group, and 16.7% and 69.5% in the pemetrexed group, respectively, but there were no significant differences (P>0.05). PFS in combination group and pemetrexed group were 4.6 months and 3.9 months respectively (P=0.09), whereas OS in the combination group was 14 months, evidently higher than in the pemetrexed group (11 months, P=0.004). Adverse responses in both groups included high blood pressure, bleeding, thrombocytopenia, anemia, elevated transaminase, diarrhea, vomiting and proteinuria, but there were no significant differences (P>0.05). Conclusions: Bevacizumab concomitant with pemetrexed has better clinical efficacy and safety, giving rise to prolonged survival time in patients with advanced NSCLC. -
Yang, Zhong-Ming;Ding, Xian-Ping;Pen, Lei;Mei, Lin;Liu, Ting 3451
Background: The serum carcinoembryonic antigen (CEA) level can reflect tumor growth, recurrence and metastasis. It has been reported that epidermal growth factor receptor (EGFR) mutations in exons 19 and 21may have an important relationship with tumor cell sensitivity to EGFR-TKI therapy. In this study, we investigated the clinical value of EGFR mutations and serum CEA in patients with non-small cell lung cancer (NSCLC). Materials and Methods: The presence of mutations in EGFR exons 19 and 21 in the tissue samples of 315 patients with NSCLC was detected with real-time fluorescent PCR technology, while the serum CEA level in cases who had not yet undergone surgery, radiotherapy, chemotherapy and targeted therapy were assessed by electrochemical luminescence. Results: The mutation rates in EGFR exons 19 and 21 were 23.2% and 14.9%, respectively, with the two combined in 3.81%. Measured prior to the start of surgery, radiotherapy, chemotherapy and targeted treatment, serum CEA levels were abnormally high in 54.3% of the patients. In those with a serum CEA level <5 ng/mL, the EGFR mutation rate was 18.8%, while with 5~19 ng/mL and${\geq}20ng/mL$ , the rates were 36.4% and 62.5%. In addition, in the cohort of patients with the CEA level being 20~49 ng/mL, the EGFR mutation rate was 85.7%, while in those with the CEA level${\geq}50ng/mL$ , the EGFR mutation rate was only 20.0%, approximately the same as in cases with the CEA level<5 ng/mL. Conclusions: There is a positive correlation between serum CEA expression level and EGFR mutation status in NSCLC patients, namely the EGFR mutation-positive rate increases as the serum CEA expression level rises within a certain range (${\geq}20ng/mL$ , especially 20~49 ng/mL). If patient samples are not suitable for EGFR mutation testing, or cannot be obtained at all, testing serum CEA levels might be a simple and easy screening method. Hence, for the NSCLC patients with high serum CEA level (${\geq}20ng/mL$ , especially 20~49 ng/mL), it is worthy of attempting EGFR-TKI treatment, which may achieve better clinical efficacy and quality of life. -
Avci, Nilufer;Cecener, Gulsah;Deligonul, Adem;Erturk, Elif;Tunca, Berrin;Egeli, Unal;Tezcan, Gulcin;Akyildiz, Elif Ulker;Bayram, Ahmet Sami;Gebitekin, Cengiz;Kurt, Ender;Evrensel, Turkkan 3457
Background: Thymomas and thymic carcinomas are rare malignancies and devising clinically effective molecular targeted therapies is a major clinical challenge. The aim of the study was to analyze BLC2 and vascular endothelial growth factor receptor (VEGFR) expression and KRAS and EGFR mutational status and to correlate them with the clinical characteristics of patients with thymomas and thymic carcinomas. Materials and Methods: A total of 62 patients (mean age:$50.4{\pm}13.2$ years) with thymomas and thymic carcinomas were enrolled. The expression of BLC2 and VEGFR in tumor cells and normal tissues was evaluated by RT-PCR. The mutational status of the KRAS and EGFR genes was investigated by PCR with sequence specific primers. Results: The BLC2 and VEGFR expression levels did not differ significantly between tumor and normal tissues. Moreover, there were no clearly pathogenic mutations in KRAS or EGFR genes in any tumor. None of the molecular markers were significantly related to clinical outcomes. Conclusions: Changes in levels of expression of BLC2 and VEGFR do not appear to be involved in thymic tumorigenesis. Moreover, our data suggest that KRAS and EGFR mutations do not play a major role in the pathogenesis of thymomas and thymic carcinomas. -
Poomtavorn, Yenrudee;Suwannarurk, Komsun;Thaweekul, Yuthadej;Maireang, Karicha 3461
Background: To determine the frequency of dysplastic lesions in the endocervical curettage (ECC) specimens of women with ASC-US and LSIL Pap and to evaluate the possible factors associated with high grade dysplasia in those ECC specimens. Materials and Methods: Two hundred and sixty patients with ASC-US and LSIL cytologic smears who underwent an ECC at the time of colposcopic examination during January 2010 and December 2012 were reviewed. Demographic and clinicopathologic data were collected. Multivariate analysis using binary logistic regression was used to identify factors that might be associated with high grade endocervical dysplasia. Results: The frequency of endocervical dysplasia was 7.7% (20 out of 260 patients). Cervical intraepithelial neoplasia (CIN) 1 and CIN 2-3 lesions in the endocervical canal were observed in 12 and 8 patients, respectively. No microinvasive or invasive cervical cancers were identified. There was no difference in the frequency of high grade endocervical dysplasia between the patients with satisfactory and unsatisfactory colposcopic examinations (1.4% vs 5.1%, respectively, p=0.087). A multivariate logistic regression analysis demonstrated a significant association between high grade CIN on ectocervical biopsy as well as LSIL cytologic smears and high grade dysplasia in endocervical canal (OR=0.046, 95%CI=0.007-0.288; p=0.001 and OR=0.154, 95%CI=0.025-0.942; p=0.043, respectively). Conclusions: The frequency of high grade endocervical dysplasia in women with ASC-US and LSIL cytologic smears was low. Therefore, routine performance of ECC in those women is debatable. High grade ectocervical dysplasia and LSIL cytologic smears may be used as predictors for high grade dysplasia in endocervical canal and ECC in these patients is reasonable. -
Oh, Myueng Guen;Kim, Jin Hwa;Han, Mi Ah;Park, Jong;Ryu, So Yeon;Choi, Seong Woo 3465
Background: Previous studies have generated conflicting evidence regarding associations between family history and survival after gastric cancer surgery. In this study, we investigated this question using a meta-analysis. Materials and Methods: To identify relevant studies, PubMed and Embase databases were searched up to June 2013. Two reviewers independently assessed search results and data extraction of included studies. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS) were calculated based on fixed- or random-effects models. Homogeneity of effects across studies was assessed using$x^2$ test statistics and quantified by$I^2$ . Results: A total of five studies were selected according to the inclusion criteria. The total number of patients included was 2,030, which ranged from 145 to 598 per study. There was no significant difference in OS by family history of cancer (HR=0.83, 95%CIs=0.50-1.38), but subgroup analysis of patients with a first-degree family history of cancer (HR=0.74, 95%CIs=0.60-0.93) and gastric cancer family history (HR=0.56, 95%CIs=0.41-0.76) tended to show better OS in these patients. Conclusions: This meta-analysis suggests that a first-degree family history of cancer or gastric cancer family history is associated with better survival of gastric cancer patients after surgery, after a systematic review of five previous studies. These results can be applied by clinicians when counselling patients regarding their risk of death from gastric cancer. Further study is needed to investigate the underlying mechanism between family history and survival in gastric cancer patients. -
Xu, Xiang-Dong;Wu, Xiao-Hou;Fan, Yan-Ru;Tan, Bing;Quan, Zhen;Luo, Chun-Li 3471
Background: Aberrant expression of the microRNA-29 family is associated with tumorigenesis and cancer progression. As transport carriers, tumor-derived exosomes are released into the extracellular space and regulate multiple functions of target cells. Thus, we assessed the possibility that exosomes could transport microRNA-29c as a carrier and correlations between microRNA-29c and apoptosis of bladder cancer cells. Materials and Methods: A total of 28 cancer and adjacent tissues were examined by immunohistochemistry to detect BCL-2 and MCL-1 expression. Disease was Ta-T1 in 12 patients, T2-T4 in 16, grade 1 in 8, 2 in 8 and 3 in 12. The expression of microRNA-29c in cancer tissues was detected by quantitative reverse transcriptase PCR (QRT-PCR). An adenovirus containing microRNA-29c was used to infect the BIU-87 human bladder cancer cell line. MicroRNA-29c in exosomes was measured by QRT-PCR. After BIU-87 cells were induced by exosomes-derived microRNA-29c, QRT-PCR was used to detect the level of microRNA-29c. Apoptosis was examined by flow cytometry and BCL-2 and MCL-1 mRNA expressions were assessed by reverse transcription-polymerase chain reaction. Western blotting was used to determine the protein expression of BCL-2 and MCL-1. Results: The expressions of BCL-2 and MCL-1 protein were remarkably increased in bladder carcinoma (p<0.05), but was found mainly in the basal and suprabasal layers in adjacent tissues. The expression of microRNA-29c in cancer tissues was negatively correlated with the BCL-2 and MCL-1. The expression level of microRNA-29c in exosomes and BIU-87 cells from the experiment group was higher than that in control groups (p<0.05). Exosome-derived microRNA-29c induced apoptosis (p<0.01). Although only BCL-2 was reduced at the mRNA level, both BCL-2 and MCL-1 were reduced at the protein level. Conclusions: Human bladder cancer cells infected by microRNA-29c adenovirus can transport microRNA-29c via exosomes. Moreover, exosome-derived microRNA29c induces apoptosis in bladder cancer cells by down-regulating BCL-2 and MCL-1. -
Huai, Jia-Ping;Ding, Jin;Ye, Xiao-Hua;Chen, Yan-Ping 3477
Objective: Patients with inflammatory bowel disease (IBD) have an increased risk of extra-intestinal cancer, whereas its impact on cholangiocarcinoma (CC) remains unknown. The aim of this study was to obtain a reliable estimate of the risk of CC in IBD patients through a meta-analysis of clinical observational studies. Methods: Relevant studies were retrieved by searching PUBMED, EMBASE and Web of Science Databases up to Dec 2013. Four population-based case-control and two cohort studies with IBD were identified. Summary relative risk (RR) and its corresponding 95% confidence interval (CI) were calculated using a random-effects model. Potential sources of heterogeneity were detected using subgroup analyses. Results: The pooled risk estimate indicated IBD patients were at increased risk of CC (RR = 2.63, 95%CI = 1.47-4.72). Moreover, the increased risk of CC was also associated with Crohn's disease (RR = 2.69, 95%CI = 1.59-4.55) and ulcerative colitis (RR = 3.40, 95%CI = 2.50-4.62). In addition, site-specific analyses revealed that IBD patients had an increased risk of intrahepatic CC (ICC) (RR = 2.61, 95%CI = 1.72-3.95) and extrahepatic CC (ECC) (RR = 1.47, 95%CI = 1.10-1.97). Conclusions: This study suggests the risk of CC is significantly increased among IBD patients, especially in ICC cases. Further studies are warranted to enable definite conclusions to be drawn. -
Srisuwan, Siriwan;Hamontri, Suttha;Kongsomboon, Kittipong;Bhamarapravatana, Kornkarn;Suwannarurk, Komsun 3483
Background: To evaluate the overtreatment rate with the see and treat approach in the management of women with abnormal cervical cytology. Materials and Methods: A retrospective review of patients with abnormal cervical cytology who underwent S&T at MSMC between January 2008 and December 2012 was conducted. Loop electrosurgical excision procedure (LEEP), histological results, cytology and colposcopic impression were analyzed to evaluate overtreatment rate, cyto-histologic correlation and related factors. Results: Average age of S&T cases was 42 years. Ninety seven percents were referred from affiliated health care providers. The study revealed 83.2% patients had HSIL or higher from cervical cytology. Correlation between HSIL and final histology was relatively low at 75% compared to other studies. Overtreatment rate was 28%. Conclusions: S&T was done in 197 patients in a tertiary care health facility with patient satisfaction. Overtreatment occurred, but the rate can be reduced with appropriate recommendations. HSIL Pap smears should be reexamined before S&T while low grade and lesser colposcopic impression groups should obtain conventional colposcopic approach for patient future reproductive benefit. -
Kudubes, Asli Akdeniz;Bektas, Murat;Ugur, Ozlem 3487
Background: This research was planned with the aim of determining the effect of symptom frequency of children with cancer on the quality of life of their parents. Materials and Methods: In gathering the research data, the Child and Parent Information Form, the Symptom Evaluation Form and the Family Version of Life Quality Scale in Cancer Patients were used. Evaluation was made by using percentage calculations, Kruskal Wallis test, Bonferroni adjusted t-test and Bonferroni adjusted Mann-Whitney U test. The significance level was accepted as 0.005. Results: Some 37.6% of the participant children were female and 62.4% were male, with an average age of$10.2{\pm}4.5$ . While 41.0% were newly diagnosed, 46.2% were in remission and 12.8% was in relapse. Highly significant differences were detected according to the symptom frequency with parent physical and psychological health, social anxiety, and spiritual wellness sub-dimensions, as well as total point averages. Conclusions: It is thought that following up the symptoms that might develop depending on cancer diagnosis and treatment and implementing nursing initiatives aimed at reducing the symptoms, knowing the importance of life quality, maintaining measures aimed at life quality and planning initiatives to increase the life quality will play a key role in maintaining and developing the health of Turkish paediatric oncology patients and their parents. -
Zhang, Qing-Mei;Shen, Ning;Xie, Sha;Bi, Shui-Qing;Luo, Bin;Lin, Yong-Da;Fu, Jun;Zhou, Su-Fang;Luo, Guo-Rong;Xie, Xiao-Xun;Xiao, Shao-Wen 3495
Melanoma-associated antigen (MAGE) family genes have been considered as potentially promising targets for anticancer immunotherapy. MAGED4 was originally identified as a glioma-specific antigen. Current knowledge about MAGED4 expression in glioma is only based on mRNA analysis and MAGED4 protein expression has not been elucidated. In the present study, we investigated this point and found that MAGED4 mRNA and protein were absent or very lowly expressed in various normal tissues and glioma cell line SHG44, but overexpressed in glioma cell lines A172,U251,U87-MG as well as glioma tissues, with significant heterogeneity. Furthermore, MAGED4 protein expression was positively correlated with the glioma type and grade. We also found that the expression of MAGED4 inversely correlated with the overall methylation status of the MAGED4 promoter CpG island. Furthermore, when SHG44 and A172 with higher methylation were treated with the DNA demethylating agent 5-aza-2'-deoxycytidine (5-AZA-CdR) reactivation of MAGED4 mRNA was mediated by significant demethylation in SHG44 instead of A172. However, 5-AZA-CdR treatment had no effect on MAGED4 protein in both SHG44 and A172 cells. In conclusion, MAGED4 is frequently and highly expressed in glioma and is partly regulated by DNA methylation. The results suggest that MAGED4 might be a promising target for glioma immunotherapy combined with 5-AZA-CdR to enhance its expression and eliminate intratumor heterogeneity. -
Chen, Xiang-Jun;Huang, Ying-De;Li, Nian;Chen, Min;Liu, Fang;Pu, Dan;Zhou, Tao-You 3503
Background: Interleukin-33 (IL-33) has recently been implicated in tumor development. Methods: Data was obtained from PubMed, EMBASE, Clinical trial, Cochrane Library, Web of Science, CNKI and Wanfang databases. After quality assessment and data extraction, a meta-analysis was performed using Review Manager 5.2 software. Results: There were eight documents included in this meta-analysis. The results showed IL33 levels to be higher in tumor patients than that in health people, but no correlations tumor stage, metastasis and survival time of tumor patients were evident. Conclusion: IL33 may be useful as an alarm factor in tumor detection and prognosis. -
Khorshidi, Fatemeh;Haghighi, Mahdi Montazer;Mojarad, Ehsan Nazemalhosseini;Azimzadeh, Pedram;Damavand, Behzad;Vahedi, Mohsen;Almasi, Shohreh;Aghdaei, Hamid Asadzadeh;Zali, Mohammad Reza 3507
Background: The prostaglandin-endoperoxide synthase 2 [PTGS2, commonly known as cyclooxygenase-2 (COX-2)] is an enzyme induced by proinflammatory stimuli that is often overexpressed in malignant tissue and involved in the synthesis of prostaglandins and thromboxanes, regulators of processes such as inflammation, cell proliferation, and angiogenesis, all relevant for cancer development. We investigated whether a functional genetic polymorphism, rs5277, in COX-2 may have a risk-modifying effect on sporadic colorectal cancer in an Iranian population. Materials and Methods: We conducted a case-control study on 167 patients with colorectal cancer and 197 cancer-free controls in Taleghani Hospital in Tehran, Iran, between 2007 and 2011. Peripheral blood samples of both groups were processed for DNA extraction and genotyping of the COX-2 gene polymorphism (rs5277) using PCR-RFLP. RFLP results were confirmed by direct sequencing. Logistic regression analysis was performed to calculate the adjusted odds ratio (OR) and 95% confidence interval (95% CI). Results: There was no significant difference in the distribution of COX-2 gene rs5277 polymorphism genotype and the allelic form, among CRC patients compared with the healthy control group (p: 0.867). Conclusions: Our results suggest that rs5277 polymorphism in COX2 could not be a good prognostic indicator for patients with CRC. -
Raungrut, Pritsana;Wongkotsila, Anusara;Lirdprapamongkol, Kriengsak;Svasti, Jisnuson;Geater, Sarayut Lucien;Phukaoloun, Monlika;Suwiwat, Supaporn;Thongsuksai, Paramee 3513
The 14-3-3 protein has been shown to be involved in the cancer process. However, there is no understanding of the relationship between 14-3-$3{\gamma}$ (14-3-3 gamma) expression and prognosis in advanced non-small cell lung cancer. In this study, we therefore investigated the association between protein levels by immunohistochemistry and clinicopathological features of advanced NSCLC patients. Survival curves were estimated using the Kaplan-Meier method and tested by log-rank. Multivariate analysis was conducted with the Cox's regression model to determine independence of factors. p values less than 0.05 were considered significant. A total 153 patients were studied, with 54.3% being stage III and 45.8% stage IV. Fifty-one cases (33.3%) were squamous cell carcinomas, and 98 cases (64.1%) were adenocarcinomas. High 14-3-$3{\gamma}$ expression was seen in 59.5% and significantly correlated with lymph node metastasis (p=0.010) and distant metastasis (p=0.017). On Kaplan-Meier analysis, high 14-3-$3{\gamma}$ expression was associated with poorer survival with a marginal trend toward significance (p=0.055). On multivariate analysis, age, treatment, and 14-3-$3{\gamma}$ expression proved to be independent prognostic parameters. In vitro experiments indicated that 14-3-$3{\gamma}$ overexpression also played a potential role in cancer invasion. In conclusion, our data suggest that 14-3-$3{\gamma}$ overexpression is associated with invasion and a poor prognosis. Therefore, 14-3-$3{\gamma}$ may be a potential prognostic marker of advanced non-small cell lung cancer. -
Vaiphei, Kim;Sinha, Saroj Kant;Kochhar, Rakesh 3519
Background: Esophageal squamous cell carcinoma (ESCC) is a common cancer with poor prognosis. It has been hypothesized that Oct4 positive radioresistant stem cells may be responsible for tumor recurrence. Hence, we evaluated Oct4 expression in ESCC in pre-treatment, post neo-adjuvant residual and post-surgical recurrent tumours. Materials and Methods: Endoscopic mucosal biopsies were used to study Oct4 expression and the observations were correlated with histological tumor grades, patient data and clinical background. Results: All patients presented with dysphagia with male predominance and a wide age range. Majority of the patients had intake of mixed diet, history of alcohol and tobacco intake was documented in less than half of the patients. Oct 4 expression was significantly higher in poorly differentiated (PDSCC) and basaloid (BSCC) subtypes than the other better differentiated tumor morphology. Oct4 was also expressed by adjoining esophageal mucosa showing low grade dysplasia and basal cell hyperplasia (BCH). Biopsies in PDSCC and BSCC groups were more likely to show a positive band for Oct4 by polymerase chain reaction (PCR). Dysplasia and BCH mucosa also showed Oct4 positivity by PCR. All mucosal biopsies with normal morphology were negative for Oct4. Number of tissue samples showing Oct4 positivity by PCR was higher than that by the conventional immunohistochemistry (p>0.05). Oct4 expression pattern correlated only with tumor grading, not with other parameters including the clinical background or patient data. Conclusions: Our observations highlighted a possible role of Oct4 in identifying putative cancer stem cells in ESCC pathobiology and response to treatment. The implications are either in vivo existence of Oct4 positive putative cancer stem cells in ESCC or acquisition of cancer stem cell properties by tumor cells as a response to treatment given, resulting ultimately an uncontrolled cell proliferation and treatment failure. -
Zhao, Jing-Yi;Ma, Xue-Lei;Li, Yan-Yan;Zhang, Bing-Lan;Li, Min-Min;Ma, Xue-Lei;Liu, Lei 3525
Objective: Fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) is a new technique for identifying different malignant tumors using different uptake values between tumor cells and normal tissues. Here we assessed the diagnostic accuracy of 18F-FDG-PET in patients with testicular cancer by pooling data of existing trials in a meta-analysis. Methods: PubMed/MEDLINE, Embase and Cochrane Central Trials databases were searched and studies published in English relating to the diagnostic value of FDG-PET for testicular cancer were collected. The summary receiver operating characteristic (SROC) curve was used to examine the FDG-PET accuracy. Results: A total of 16 studies which included 957 examinations in 807 patients (median age, 31.1 years) were analyzed. A meta-analysis was performed to combine the sensitivity and specificity and their 95% confidence intervals (CIs), from diagnostic odds ratio (DOR), positive likelihood ratios (PLR), negative likelihood ratio (NLR). SROC were derived to demonstrate the diagnostic accuracy of FDG-PET for testicular cancer. The pooled sensitivity and specificity were 0.75 (95% confidence interval (CI), 0.70-0.80) and 0.87 (95% CI, 0.84-0.89), respectively. The pooled DOR was 35.6 (95% CI, 12.9-98.3). The area under the curve (AUC) was 0.88. The pooled PLR and pooled NLR were 7.80 (95% CI, 3.73-16.3) and 0.31 (95% CI, 0.23-0.43), respectively. Conclusion: In patients with testicular cancer, 18F-FDG-PET demonstrated a high SROC area, and could be a potentially useful tool if combined with other imaging methods such as MRI and CT. Nevertheless, the literature focusing on the use of 18F-FDG-PET in this setting still remains limited. -
Niu, Hui-Yan;Niu, Chun-Ying;Wang, Jia-He;Zhang, Yi;He, Ping 3533
Background: Breast cancer is one of the most common cancers in women in the world. Health-related quality of life (HRQL) at treatment endpoint in cancer clinical trials is widely considered to be increasingly important. The aim of this review was to provide a literature-based assessment of the validity, reliability and responsiveness of breast cancer-specific HRQL instruments in women breast cancer patients. Materials and Methods: The databases consulted were Medline, PubMed, and Embase. The inclusion criteria required studies to: (1) involve use of HRQL measures; (2) cover women with breast cancer under standard treatment (surgery, radiation therapy, chemotherapy, hormone therapy, and targeted therapy); (3) involve the validity, reliability, or responsiveness of HRQL; (4) deal with validation of breast cancer-specific HRQL instruments. Results: A total of 16 studies were identified through the literature search that met the 4 inclusion criteria. Some seven instruments were assessed among these 16 studies: EORTC QLQ-BR23, FACT-B, FACT-ES, HFRDIS, LSQ-32, QLICP-BR, and SLDS-BC. EORTC QLQ-BR23, FACT-B, LSQ-32, QLICP-BR, and SLDS-BC are more general breast cancer-specific HRQL instruments. FACT-EB is the endocrine subscale combined with FACT-B in order to measure the side effects and putative benefits of hormonal treatment administered in breast cancer patients. HFRDIS is the HRQL measure focusing on hot flash concerns. Conclusions: This paper provides an overall understanding on the currently available breast cancer-specific HRQL instruments in women breast cancer patients. -
Seker, Mehmet Metin;Seker, Ayse;Aksoy, Sercan;Ozdemir, Nuriye;Uncu, Dogan;Zengin, Nurullah 3537
Background: Osteosarcomas are the most common solid malignancies of bone. In the last two decades there have been no concrete developments in their systemic treatment. In this trial we aimed to present our osteosarcoma patient clinical and demographic outcomes. Materials and Methods: Patients treated and followed up for osteosarcoma in Ankara Numune Education and Research Hospital from 2002 to 2012 were reviewed retrospectively. Results: A total of 21 patients (15 male, 6 female) were diagnosed with osteosarcoma. The disease was located at extremities in 76% and in 14% was metastatic at the time of diagnosis. Median disease free survival (DFS) was 36 months in non-metastatic patients and median progression free survival (PFS) was 2 months in metastatic patients (p<0.0001). Median overall survival (OS) was 80 months and 4 months, respectively (p=0.012). There were no survival differences in terms of presentation with pathological fracture, tumor size, tumor grade, alkaline phosphatase and lactate dehydrogenase level and type of chemotherapy regimen. Conclusions: Tumor site and stages are the most important prognostic factors for osteosarcoma. Extremity primary tumors have beter survival rates than non-extremity tumors. As a result of the use of effective chemotherapy the long term survival rates have improved from 10-20% to 60-70% in the last decades but we need more active agents, especially for metastatic cases. -
TEL-AML1 fusion oncogene (t 12; 21) is the most common chromosomal abnormality in childhood acute lymphoblastic leukemia (ALL). This translocation is associated with a good prognosis and rarely shows chemotherapeutic resistance to 3-drug based remission induction phase of treatment as well as overall treatment. Thus, the higher the frequency of this fusion oncogene, the easier to manage childhood ALL in a given region with less intensive chemotherapy. Although global frequency of TEL-AML1 has been reported to be 20-30%, a very low frequency has been found in some geographical regions, including one study from Lahore, Punjab, Pakistan and others from India. The objective of present study was to investigate if this low frequency of TEL-AML1 in pediatric ALL is only in Lahore region or similar situation exists at other representative oncology centers of Pakistan. A total of 167 pediatric ALL patients were recruited from major pediatric oncology centers situated in Lahore, Faisalabad, Peshawar and Islamabad. Patients were tested for TEL-AML1 using nested reverse transcription polymerase chain reaction (RT-PCR). Only 17 out of 167 (10.2%) patients were found to be TEL-AML1 positive. TEL-AML1+ALL patients had favorable prognosis, most of them (82.4%, 14/17) showing early remission and good overall survival. Thus, our findings indicate an overall low frequency of TEL-AML1 in Pakistan pediatric ALL patients, in accordance with lower representation of this prognostically important genetic abnormality in other less developed countries, specifically in south Asia, thus associating it with poor living standards in these ethnic groups. It also indicates ethnic and geographical differences in the distribution of this prognostically important genetic abnormality among childhood ALL patients, which may have a significant bearing on ALL management strategies in different parts of the world.
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Background: The prognostic value of serum alkaline phosphatase (S-ALP) has not been fully validated for nasopharyngeal carcinoma (NPC). Materials and Methods: S-ALP levels were measured in 601 patients newly diagnosed with NPC before radical treatment, and possible associations of these levels with 5-year overall survival (OS) and tumor-free survival (TFS) were explored using univariate and multivariate analyses. Results: Elevated pretreatment S-ALP (>85 U/L) was significantly less frequent among patients classified as T1+2 or stage I+II than among those classified as T3+4 or stage III+IV. Multivariate analysis showed that elevated pretreatment S-ALP (>85 U/L), age, T classification and N stage were independent predictors of poor OS and TFS. Conclusions: Pretreatment S-ALP may be a reliable biomarker to evaluate the long-term prognosis of patients with NPC.
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Li, Bo;Zhao, Xin;Dai, Shao-Chun;Cheng, Wen 3555
Background: The triple-negative breast cancer (TNBC) is an aggressive cancer characterized by the absence of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). Preoperative mammography and ultrasound features of TNBC may potentially suggest characteristics of the disease and assist in treatment decisions. Materials and Methods: The study covered 153 patients with TNBC from May 2011 to May 2012 who were confirmed by postoperative pathology results in our hospital. We compared the radiological findings among the patients and sought to determine the significant iconographic features. The biomarkers p53 and Ki-67 are regarded as significant factors in TNBC. They were therefore used to divide the TNBC into four groups for assessment of relationships with TNBC imaging features. Results: On mammography, most TNBCs exhibit obscure (44.3%) masses. On ultrasound, the majority of masses (95.4%) were predominantly indistinct (50.7%), irregular (76.0%) or featuring posterior echo enhancement/shadowing. Color Doppler flow imaging (CDFI) emphasized hypervascular (32.9%) masses. Differences in CDFI by ultrasound among the four groups were statistically significant (p=0.009). There were obvious differences in the percentages of spiculated margin (p=0.049) and intensive posterior echo (p=0.006) with spotty flow imaging by ultrasound between the Ki-67 (+) p53 (+) and other groups. Conclusions: A combination of mammography and ultrasound revealed the imaging characteristics of TNBC included an obscure mass with less attenuated posterior echoes and some vascularity. A worse prognosis was associated with spiculated margin and intensive posterior echoes with spotty flow imaging. -
Dizman, Aysen;Coskun-Breuneval, Mehtap;Altinisik-Inan, Gonca;Olcay, Gokce Kaan;Cetindag, Mehmet Faik;Guney, Yildiz 3561
Background: Recurrent nasopharyngeal carcinoma (NPC) after previous radiotherapy is challenging. There is no standard approach for salvage treatment. Here we present toxicity and treatment results for recurrent NFC patients who underwent fractionated stereotactic radiotherapy (FSRT) as second line radiotherapy (RT). Materials and Methods: Between April 2009 and July 2012, 24 patients, with a male to female ratio of 3:1, were treated with CykerKnife$^{(R)}$ FSRT for recurrent NFC in our institution. Seven out of 24 patients had metastatic recurrent disease. Median age was 53 years (range, 20-70 years). Initial RT dose was 70Gy. The time period between initial RT and FSRT was a median of 33.2 months. The median prescription dose for FSRT was 30Gy (range, 24-30 Gy) in a median of 5 fractions (range, 4-6). Results: The median follow-up for all patients was 19.5 months (IQR: 12.2.-29.2 months). The locoregional control; progression free survival and overall survival (OS) rates for 1-, 2- and 3-year were 64%, 38%, 21%; 60%, 30%, 17% and 83%, 43%, 31%, respectively. Median OS for the entire cohort was 22 months (95% CI: 16.5-27.5). On multivariate analysis recurrent tumor stage was the only prognostic factor for OS (p=0.004). One patient exhibited grade III temporal lobe necrosis. One died because of grade IV mucositis and overlapping infection. Conclusions: The treatment of recurrent NPC is controversial. Fractionated stereotactic radiotherapy is promising. However, the published trials are heterogeneous with respect to the selection criteria and treatment details. Prospective studies with long term follow-up data are warranted. -
Somboon, Krittapong;Siramolpiwat, Sith;Vilaichone, Ratha-Korn 3567
Background: Hepatocellular carcinoma (HCC) is one of the most common cancers in men and the third most common cancer in woman in Thailand. This retrospective study was designed to assess the prevalence, clinical manifestations, treatment outcomes and prognosis of HCC in the central region of Thailand. Materials and Methods: The authors retrospectively reviewed all HCC patients aged more than 15 years old in Thammasat university hospital (TUH) during the period from January 2007 to December 2012. Clinical information, biochemical tests and radiologic findings were collected from review of medical records. Results: There were 308 patients with HCC, which accounted for the prevalence of 5.19% of all cancers diagnosed in TUH during the study period. Of these, 125 (40.5%) had complete information retrievable from their medical records and met the inclusion criteria, 99 (79.2%) were males. The mean age was 57.4 years. A quarter of HCC patients in this study presented without any symptom before diagnosis. The common clinical presentations in the remaining patients were hepatomegaly 64/125 (51.2%), abdominal pain 56/125 (44.8%) and ascites 16/125 (20.8%). Cirrhosis was seen in almost all patients (92.8%). The most common causes of HCC in this study were chronic hepatitis B (49.6%) and C (19.2%). Based on Barcelona Clinic Liver Cancer staging, 75.4% presented at intermediate or late stage. Patients receiving curative therapy with either surgical treatment or radiofrequency ablation had significantly longer survival time after the HCC diagnosis than the palliative therapy group (11.0 months vs 4.0 months, p value= 0.004). The mean survival time after the HCC diagnosis was 10.5 months. Conclusions: The common causes of HCC in central region of Thailand were chronic hepatitis B and C. Surgical therapy or RFA seemed to provide better outcomes than other treatments but only in patients with early stage lesions. Most of the patients in this study presented with advanced diseases and had grave prognosis. Appropriate screening patients at risk for HCC might be an appropriate way to achieve early diagnosis and improve the treatment outcome. -
Akhavan, Ali;Binesh, Fariba;Heidari, Samaneh 3571
Background: Brain metastasis occurs when cancerous cells come from a known (or sometimes an unknown) primary tumor to the brain and implant and grow there. This event is potentially lethal and causes neurologic symptoms and signs. These patients are treated in order to decrease their neurologic problems, increase quality of life and overall survival. Materials and Methods: In this study we evaluated clinical characteristics of 206 patients with brain metastases referred to our center from 2004 to 2011. Results: The mean age was 53.6 years. The primary tumors were breast cancer (32%), lung cancer (24.8%), lymphoma (4.4%), sarcoma (3.9%), melanoma (2.9%), colorectal cancer (2.4%) and renal cell carcinoma (1.5%). In 16.5% of the patients, brain metastasis was the first presenting symptom and the primary site was unknown. Forty two (20.4%) patients had a single brain metastasis, 18 patients (8.7%) had two or three lesions, 87 (42.2%) patients had more than three lesions. Leptomeningeal involvement was seen in 49 (23.8%) patients. Thirty five (17%) had undergone surgical resection. Whole brain radiation therapy was performed for all of the patients. Overall survival was 10.1 months (95%CI; 8.65-11.63). One and two year survival was 27% and 12% respectively. Conclusions: Overall survival of patients who were treated by combination of surgery and whole brain radiation therapy was significantly better than those who were treated with whole brain radiation therapy only [13.8 vs 9.3 months (p=0.03)]. Age, sex, primary site and the number of brain lesions did not show significant relationships with overall survival. -
Nan, Yi-Nan;Zhu, Jing-Yan;Tan, Yan;Zhang, Qi;Jia, William;Hua, Qian 3575
TDP-43 is a ubiquitously expressed DNA/RNA binding protein that has recently attracted attention for its involvement in neurodegenerative diseases. While TDP-43 has been found to participate in various important cellular activities including stress and apoptosis, little is known about its role in cancer cells. Here we report that staurosporine (STS) induced apoptosis in U87 glioma cells is associated with rapid downregulation of TDP-43 at both mRNA and protein levels. The latter is dependent on activation of caspase 3. More importantly, we have shown that knockdown of TDP-43 by specific siRNA dramatically enhanced cytotoxicity of STS. These results suggest that normal level of TDP-43 may be protective for cancer cells under apoptotic insult. -
Ji, Ai-Jun;Liu, Sheng-Lin;Ju, Wen-Zheng;Huang, Xin-En 3581
Aim: To investigate the effects of tetramethypyrazine (TMP) on proliferation and apoptosis of the human gastric carcinoma cell line 7901 and its possible mechanism of action. Methods: The viability of TMP-treated 7901 cells was measured with a 3-(4, 5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT) and cell apoptosis was analyzed by flow cytometry. The distribution of cells in different phases of cell cycle after exposure of TMPs was analyzed with flow cytometry. To investigate the molecular mechanisms of TMP-mediated apoptosis, the expression of NF-${\kappa}Bp65$ , cyclinD1 and p16 in SGC-7901 cells was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. Results: TMP inhibited the proliferation of human gastric carcinoma cell line 7901 in dose and time dependent manners. Cell growth was suppressed by TMP at different concentrations (0.25, 0.5, 1.0, 2.0 mg/ml), the inhibition rate is 0.46%, 4.36%, 14.8%, 76.1% (48h) and 15.5%, 18.5%, 41.2%, 89.8% (72h) respectively. When the concentration of TMPs was 2.0mg/ml, G1-phase arrest in the SGC-7901 cells was significant based on the data for cell cycle distribution. RT-PCR demonstrated that NF-${\kappa}Bp65$ and cyclin D1 mRNA expression was significantly down-regulated in 7901 cells treated with 2.0 mg/ml TMP for 72h (p<0.05), while the p16 mRNA level was up-regulated (p<0.05). The protein expression of NF-${\kappa}Bp65$ and cyclin D1 decreased gradually with the increase in TMP concentration, compared with control cells (p<0.05), while expression of protein p16 was up-regulated (p<0.01). Conclusion: TMP exhibits significant anti-proliferative and pro-apoptotic effects on the human gastric carcinoma cell line SGC-7901. NF-${\kappa}Bp65$ , cyclinD1 and p16 may also play important roles in the regulation mechanisms. -
Roy, Soumyajit;Mallick, Supriya;Raza, Md. Waseem;Haresh, Kunhi Parambath;Gupta, Subhash;Sharma, Daya Nand;Julka, Pramod Kumar;Rath, Goura Kisore 3587
Burden of cancer is progressively increasing in developing countries like India which has also led to a steep rise in toxicity due to anti-cancer therapy. A cross-sectional analysis was here conducted for patients with different malignancies (except leukaemia) who while undergoing radical anti-cancer therapy were admitted to our oncology ward from January-July 2013. In a total of 280 patients, the total number of toxicity events was 473. Nine patients expired over this time period. Among the events, grade 2 anaemia the most common (n=189) while the most common grades of neutropenia and thrombocytopenia were grade 4 (n=114) and grade 2 (n=48), respectively. Among the tracable microbial etiologies, gram negative bacteria were the most commonly found pathogens. Treatment interruptions took place in 240 patients (median duration=8.8 days). Prolonged hospital admission, intensive care and artificial ventilation support was needed to be given in 48, 7 and 13 patients respectively. Advanced NSCLC, KPS <70, pancytopenia and artificial ventilation requirement were found to have a significant impact on death. Such studies show the prevailing practice from institutes of our country and may guide us formulating a guideline for managing such toxicities for this part of the world. -
Gunawan, Stefanus;Wolters, Emma;Dongen, Josephine Van;De Ven, Peter Van;Sitaresmi, Mei;Veerman, Anjo;Mantik, Max;Kaspers, Gertjan;Mostert, Saskia 3593
Background: Efficacy of childhood cancer treatment in low-income countries may be impacted by parents' and health-care providers' perspectives on chemotherapy-related side-effects. This study explores prevalence and severity of side-effects in childhood cancer, and compares health beliefs about side-effects between parents and health-care providers, and between nurses and doctors in Indonesia. Materials and Methods: Semi-structured questionnaires were filled in by 40 parents and 207 health-care providers in an academic hospital. Results: Parents exporessed a desire to receive more information about side-effects (98%) and worried about this aspect of treatment (90%), although side-effects were less severe than expected (66%). The most frequent was behavior alteration (98%) and the most severe was hair loss. Only 26% of parents consulted doctors about side-effects. More parents, compared to health-care providers, believed that medicines work better when side-effects are more severe (p<0.001), and accepted severe side-effects (p=0.021). More health-care providers, compared to parents, believed that chemotherapy can be stopped or the dosage altered when there are side-effects (p=0.011). More nurses, compared to doctors, stated that side-effects were unbearable (p=0.004) and made them doubt efficacy of treatment (p<0.001). Conclusions: Behavior alteration is the most frequent and hair loss the most severe side-effect. Apparent discrepancies in health beliefs about side-effects exist between parents and health-care providers. A sustainable parental education program about side-effects is recommended. Health-care providers need to update and improve their knowledge and communication skills in order to give appropriate information. Suchmeasures may improve outcome of childhood cancer treatment in low-income countries, where adherence to therapy is a major issue. -
He, Fei;Zheng, Ling-Ling;Luo, Wen-Ting;Yang, Rong;Xu, Xiao-Qin;Cai, Lin 3601
Single nucleotide polymorphisms located at microRNA (miRNA)-binding sites are likely to affect the expression of miRNA targets and may contribute to the susceptibility of humans to common diseases. Here 335 candidate lung cancer-related inflammatory genes were selected according to the existing literature and database. We identified putative miRNA-binding sites of 149 genes by specialised algorithms and screened SNPs in the 3'UTRs of these genes. By calculating binding free energy, we sorted 269 SNPs on the basis of the possibility of prediction. The proposed approach could help to easy the identification of functionally relevant SNPs and minimize the workflow and the costs. -
Qin, Ling-Yan;Zhao, Li-Gang;Chen, Xu;Li, Ping;Yang, Zheng;Mo, Wu-Ning 3607
Background: In recent years, numerous studies have been performed to investigate the CCND1 G870A gene polymorphism impact on brain tumors susceptibility. Unfortunately, the results of previous studies were inconsistent. Therefore, we performed a meta-analysis to derive a more precise estimation of any association. Materials and Methods: We conducted a search in PubMed, Embase and CNKI covering all published papers up to November, 2013. Odds ratios (ORs) and their 95% confidence intervals (95%CIs) were applied to assess associations. Results: A total of 6 publications including 9 case-control studies met the inclusion criteria. The pooled ORs for the total included studies showed significant association among comparison A vs G (OR= 1.246, 95%CI= 1.092-1.423, p= 0.001), homozygote comparison AA vs GG (OR= 1.566, 95%CI= 1.194-2.054, p= 0.001), heterozygote comparison AG vs GG (OR= 1.290, 95%CI= 0.934-1.782, p= 0.122), dominant model AA/GA vs GG (OR= 1.381, 95%CI= 1.048-1.821, p= 0.022) and recessive model AA vs GA/GG (OR= 1.323, 95%CI= 1.057-1.657, p= 0.015) especially in glioma. Conclusions: CCND1 G870A polymorphism may increase brain tumor risk, especially for gliomas. However, more primary large scale and well-designed studies are still required to evaluate the interaction of CCND1 G870A polymorphism with brain tumor risk. -
Wang, Feng;Xuan, Xiao-Yan;Yang, Xuan;Cao, Lei;Pang, Li-Na;Zhou, Ran;Fan, Qin-Xia;Wang, Liu-Xing 3613
Stathmin, also called oncoprotein 18, is a founding member of the family of microtubule-destabilizing proteins that play a critical role in the regulation of mitosis. At the same time stathmin has been recognized as one of responsible factors in cancer cells. The aim of this study was to assess stathmin status, its correlations with clinicopathological parameters and its role as a progosnostic marker in EC patients. The protein and mRNA levels of stathmin were examined byimmunohistochemistry (IHC) and in situ hybridization in 100EC tissues and adjacent noncancerous tissues. mRNA and protein expression of stathmin in three EC cell lines(EC9706, ECa109, EC1 commonly used in research) were also analyzed using immunocytochemistry, western blot and in situ hybridization. The prognostic value of Stathmin expression within the tumor tissues were assessed by Cox regression and Kaplan-Meier analysis. We showed that stathmin expression was significantly higher in EC tissues than in adjacent noncancerous tissues. High stathmin immunostaining score in the EC was positively correlated with tumor differentiation, Tumor invasion, Lymph node metastases, and TNM stage. In addition, we demonstrated that three EC cell lines examined, were constitutively expressing a high level of stathmin. Of those, EC-1 showed the strongest mRNA and protein expression for the stathmin analyzed. Kaplan-Meier analysis showed that significantly longer 5-year survival rate was seen in EC patients with high Stathmin expression, compared to those with low expression of Stathmin expression. Furthermore, multivariate Cox proportional hazard analyses revealed that Stathmin was an independent factors affecting the overall survival probability. In conclusion, our data provide a basis for the concept that stathmin might be associated with EC development and progression. High levels of Stathmin expression in the tumor tissues may be a good prognostic marker for patients with EC. -
Rai, Bhavana;Dhanireddy, Bhaswanth;Patel, Firuza Darius;Kumari, Reena;Oinam, Arun Singh;Simha, Vijai;Sharma, Suresh 3619
Background: The aim of the study was to evaluate the vaginal dose and toxicity in patients of cervical cancer treated with image guided brachytherapy at our institute. Materials and Methods: Thirty-five patients treated with image based brachytherapy for cervical cancer were included. Vaginal contouring was done on MRI at brachytherapy and with CT scans of subsequent brachytherapy fractions. Dose volume parameters (DVH) were reported in accordance with the GEC-ESTRO guidelines. These were correlated with vaginal toxicity (assessed by CTCAE version 3) and quality of sexual life assessed at one year of completion of treatment. Results: Vaginal shortness was observed in 22 out of 30 (62.8%) patients, Nine (25.7%) had vaginal dryness and in 10 (28.5%) patients, there was contact bleeding. No association could be demonstrated between the dose volume parameters and vaginal toxicity in the present study. Conclusions: The lack of association between dose volume parameters of vagina with vaginal morbidity may be due to uncertainties involved in the delineation of vaginal wall and dosimetry. Future research is required to accurately define vaginal dose distribution to study its correlation with vaginal morbidity. Vaginal morbidity needs to be documented in order to improve the sexual outcome in these patients. -
Ozalp, Sabit Sinan;Telli, Elcin;Oge, Tufan;Tulunay, Gokhan;Boran, Nurettin;Turan, Taner;Yenen, Mufit;Kurdoglu, Zehra;Ozler, Ali;Yuce, Kunter;Ulker, Volkan;Arvas, Macit;Demirkiran, Fuat;Bese, Tugan;Tokgozoglu, Nedim;Onan, Anil;Sanci, Muzaffer;Gokcu, Mehmet;Tosun, Gokhan;Dikmen, Yilmaz;Ozsaran, Aydin;Terek, Mustafa Cosan;Akman, Levent;Yetimalar, Hakan;Kilic, Derya Sakarya;Gungor, Tayfun;Ozgu, Emre;Yildiz, Yunus;Kokcu, Arif;Kefeli, Mehmet;Kuruoglu, Serkan;Yuksel, Hasan;Guvenal, Tevfik;Hasdemir, Pinar Solmaz;Ozcelik, Bulent;Serin, Serdar;Dolanbay, Mehmet;Arioz, Dagistan Tolga;Tuncer, Nadire;Bozkaya, Hasan;Guven, Suleyman;Kulaksiz, Deniz;Varol, Fusun;Ali, Yanik;Ogurlu, Gonca;Simsek, Tayyup;Toptas, Tayfun;Dogan, Selen;Camuzoglu, Hakan;Api, Murat;Guzin, Kadir;Eray, Caliskan;Doger, Emek 3625
Background: To evaluate the incidence, diagnosis and management of GTN among 28 centers in Turkey. Materials and Methods: A retrospective study was designed to include GTN patients attending 28 centers in the 10-year period between January 2003 and May 2013. Demographical characteristics of the patients, histopathological diagnosis, the International Federation of Gynecology and Obstetrics (FIGO) anatomical and prognostic scores, use of single-agent and multi-agent chemotherapy, surgical interventions and prognosis were evaluated. Results: From 2003-2013, there were 1,173,235 deliveries and 456 GTN cases at the 28 centers. The incidence was calculated to be 0.38 per 1,000 deliveries. According to the evaluated data of 364 patients, the median age at diagnosis was 31 years (range, 15-59 years). A histopathological diagnosis was present for 45.1% of the patients, and invasive mole, choriocarcinoma and PSTTs were diagnosed in 22.3% (n=81), 18.1% (n=66) and 4.7% (n=17) of the patients, respectively. Regarding final prognosis, 352 (96.7%) of the patients had remission, and 7 (1.9%) had persistence, whereas the disease was mortal for 5 (1.4%) of the patients. Conclusions: Because of the differences between countries, it is important to provide national registration systems and special clinics for the accurate diagnosis and treatment of GTN. -
Wei, Xiao-Bing;Jin, Tian-Bo;Li, Gang;Geng, Ting-Ting;Zhang, Jia-Yi;Chen, Cui-Ping;Gao, Guo-Dong;Chen, Chao;Gong, Yong-Kuan 3629
Background: Glioblastoma (GBM) is an immunosuppressive tumor whose median survival time is only 12-15 months, and patients with GBM have a uniformly poor prognosis. It is known that heredity contributes to formation of glioma, but there are few genetic studies concerning GBM. Materials and Methods: We genotyped six tagging SNPs (tSNP) in Han Chinese GBM and control patients. We used Microsoft Excel and SPSS 16.0 statistical package for statistical analysis and SNP Stats to test for associations between certain tSNPs and risk of GBM in five different models. ORs and 95%CIs were calculated for unconditional logistic-regression analysis with adjustment for age and gender. The SHEsis software platform was applied for analysis of linkage disequilibrium, haplotype construction, and genetic associations at polymorphism loci. Results: We found rs891835 in CCDC26 to be associated with GBM susceptibility at a level of p=0.009. The following genotypes of rs891835 were found to be associated with GBM risk in four different models of gene action: i) genotype GT (OR=2.26; 95%CI, 1.29-3.97; p=0.019) or GG (OR=1.33; 95%CI, 0.23-7.81; p=0.019) in the codominant model; ii) genotypes GT and GG (OR=2.18; 95%CI, 1.26-3.78; p=0.0061) in the dominant model; iii) GT (OR=2.24; 95%CI, 1.28-3.92; p=0.0053) in the overdominant model; iv) the allele G of rs891835 (OR=1.85; 95%CI, 1.14-3.00; p=0.015) in the additive model. In addition, "CG" and "CGGAG" were found by haplotype analysis to be associated with increased GBM risk. In contrast, genotype GG of CCDC26 rs6470745 was associated with decreased GBM risk (OR=0.34; 95%CI, 0.12-1.01; p=0.029) in the recessive model. Conclusions: Our results, combined with those from previous studies, suggest a potential genetic contribution of CCDC26 to GBM progression among Han Chinese. -
Wu, Jun-Qing;Li, Yu-Yan;Ren, Jing-Chao;Zhao, Rui;Zhou, Ying;Gao, Er-Sheng 3635
Aim: To determine whether induced abortion (IA) increases breast cancer (BC) risk. Materials and Methods: A population-based case-control study was performed from Dec, 2000 to November, 2004 in Shanghai, China, where IA could be verified through the family planning network and client medical records. Structured questionnaires were completed by 1,517 cases with primary invasive epithelial breast cancer and 1,573 controls frequency-matched to cases for age group. The information was supplemented and verified by the family planning records. Statistical analysis was conducted with SAS 9.0. Results: After adjusting for potential confounders, induced abortions were not found to be associated with breast cancer with OR=0.94 (95%CI= 0.79-1.11). Compared to parous women without induced abortion, parous women with 3 or more times induced abortion (OR=0.66, 95%CI=0.46 to 0.95) and women with 3 or more times induced abortion after the first live birth (OR=0.66, 95%CI =0.45 to 0.97) showed a lower risk of breast cancer, after adjustment for age, level of education, annual income per capita, age at menarche, menopause, parity times, spontaneous abortion, age at first live birth, breast-feeding, oral contraceptives, hormones drug, breast disease, BMI, drinking alcohol, drinking tea, taking vitamin/calcium tablet, physical activity, vocation, history of breast cancer, eating the bean. Conclusions: The results suggest that a history of induced abortions may not increase the risk of breast cancer. -
Karaca, Halit;Bozkurt, Oktay;Ozaslan, Ersin;Baldane, Suleyman;Berk, Veli;Inanc, Mevlude;Duran, Ayse Ocak;Dikilitas, Mustafa;Er, Ozlem;Ozkan, Metin 3641
The present study aimed to determine the effect of oral${\beta}$ -glucan on mucositis and leukopenia in 62 consecutive patients with colorectal cancer treated with an adjuvant FOLFOX-4 regimen. The patients were retrospectively evaluated in 2 groups: one group received${\beta}$ -glucan and the other did not (control group). Leucocytes, neutrophils, and platelets were evaluated before and 1 week after chemotherapy and oral mucositis and diarrhea were noted. Leucocyte and neutrophil counts after chemotherapy in the${\beta}$ -glucan group were$7,300/mm^3$ and$3,800/mm^3$ , respectively, and the reductions, as compared to baseline, were not significant (p=0.673 and 0.784). The median platelet count was$264,000/mm^3$ after chemotherapy in the${\beta}$ -glucan group and the reduction, as compared to baseline, was borderline significant (p=0.048). In the control group, reduction in leucocyte, neutrophil, and platelet counts was statistically significant. Oral mucositis and diarrhea were less common in the${\beta}$ -glucan group. We conclude that${\beta}$ -glucan can be used to reduce the adverse effects of chemotherapy. -
Matsumoto, Kazuhiro;Hagiwara, Masayuki;Hayakawa, Nozomi;Tanaka, Nobuyuki;Ito, Yujiro;Maeda, Takahiro;Ninomiya, Akiharu;Nagata, Hirohiko;Nakamura, So 3645
The aim of this study was to evaluate the efficacy of third-line combined androgen blockade (CAB) therapy for castration-resistant prostate cancer that relapsed after primary and second-line CAB. We retrospectively reviewed the medical records of 52 patients who received first-, second-, and third-line CAB therapy (medical or surgical castration, plus steroidal antiandrogen of chlormadinone acetate, or nonsteroidal antiandrogen of flutamide or bicalutamide). For cumulative analysis, we searched the PubMed database and identified a total of 50 cases published in English. Including our cases, this provided a total of 102 cases for analysis. In our study cohort, 11 cases (21.2%) achieved more than 50% reduction of serum prostate-specific antigen (PSA) on initiation of third-line CAB. We found that third-line CAB with nonsteroidal antiandrogen after second-line CAB with steroidal antiandrogen exhibited favorable results, with a positive response in six of 13 patients (46.2%). Cumulative analysis findings were comparable. Regarding the timing of third-line CAB administration, 15 patients had started at a PSA equal to or less than 4.0 ng/ml, and eight of them (53.3%) showed a positive response to treatment, compared to only three of 37 patients (8.1%) whose PSA at the initiation of third-line therapy was higher than 4.0 ng/ml (p<0.001). We conclude that third-line CAB with nonsteroidal antiandrogen would be particularly useful for patients whose cancer progressed after second-line CAB with steroidal antiandrogen. The timing of treatment seems to be important because the higher the PSA at the start of third-line therapy, the lower the PSA response rate. -
Ji, Yu-Bin;Ling, Na;Zhou, Xiao-Jun;Mao, Yun-Xiang;Li, Wen-Lan;Chen, Ning 3651
Hepatocellular carcinoma (HCC) has a relatively higher incidence in many countries of Asia. Globally, HCC has a high fatality rate and short survival. Epirubicin, a doxorubicin analogue, may be administered alone or in combination with other agents to treat primary liver cancer and metastatic diseases. However, the toxic effects of epirubicin to normal tissues and cells have been one of the major obstacles to successful cancer chemotherapy. Here, we investigated the effects of epirubicin in combination with kappa-selenocarrageenan on mice with H22 implanted tumors and HepG-2 cell proliferation, immune organ index, morphology, cell cycle and related protein expressions in vivo and in vitro with sequential drug exposure. The inhibitory rate of tumor growth in vivo was calculated. Drug sensitivity was measured by MTT assay, and the King's principle was used to evaluate the interaction of drug combination. Morphological changes were observed by fluorescent microscopy. Cell cycle changes were analyzed by flow cytometry. Expression of cyclin A, Cdc25A and Cdk2 were detected by Western blotting. In vivo results demonstrated that the inhibitory rate of EPI combined with KSC was higher than that of KSC or EPI alone, and the Q value indicated an additive effect. In addition, KSC could significantly raise the thymus and spleen indices of mice with H22 implanted tumors. In the drug sensitivity assay in vitro, exposure to KSC and EPI simultaneously was more effective than exposure sequentially in HepG-2 cells, while exposure to KSC prior to EPI was more effective than exposure to EPI prior to KSC. Q values showed an additive effect in the simultaneous group and antagonistic effects in the sequential groups. Morphological analysis showed similar results to the drug sensitivity assay. Cell cycle analysis revealed that exposure to KSC or EPI alone arrested the cells in S phase in HepG-2 cells, exposure to KSC and EPI simultaneously caused accumulation in the S phase, an effect caused by either KSC or EPI. Expression of cyclin A, Cdc25A and Cdk2 protein was down-regulated following exposure to KSC and EPI alone or in combination, exposure to KSC and EPI simultaneously resulting in the lowest values. Taken together, our findings suggest that KSC in combination with EPI might have potential as a new therapeutic regimen against HCC. -
Zhou, Cui;Jiang, Song-Song;Wang, Cui-Yan;Li, Rong;Che, Hui-Lian 3659
To assess inhibition mechanisms of a Phellinus igniarius (PI) extract on cancer, C57BL/6 mice were orally treated with PI extractive after or before implanting H22 (hepatocellular carcinoma ) or B16 (melanoma) cells. Mice were orally gavaged with different doses of PI for 36 days 24h after introduction of H22 or B16 cells. Mice in another group were orally treated as above daily for 42 days and implanted with H22 cells on day 7. Then the T lymphocyte, antibody, cytokine, LAK, NK cell activity in spleen, tumor cell apoptosis status and tumor inhibition in related organs, as well as the expression of iNOS and PCNA in tumor tissue were examined. The PI extract could improve animal immunity as well as inhibit cancer cell growth and metastasis with a dose-response relationship. Notably, PI's regulation with the two kinds of tumor appeared to occur in different ways, since the antibody profile and tumor metastasis demonstrated variation between animals implanted with hepatocellular carcinoma and melanoma cells. -
Alshammari, Atika Hazzaa;Shalaby, Manal Aly;Alanazi, Mohammad Saud;Saeed, Hesham Mahmoud 3667
Background: colorectal cancer (CRC) is the third most common type of cancers and the fourth leading cause of death worldwide. In Saudi Arabia, CRC accounts for 8.5% of all tumors; it ranks first among all cancers in males and third among females. The aim of this study was to link between different PARP-1 mutations and risk of CRC in Saudi population and to determine common variants of PARP-1 in Saudi CRC patients and normal individuals. Materials and Methods: DNA samples were isolated from fifty CRC patients and from a comparable number of control subjects then sequenced to detect different variations present in exons 3, 17, and 21 of the PARP-1 gene. Results and Conclusions: When comparing the genotype and allele frequencies of all detected SNPs in CRC patients with those in controls, we found none were significantly different for all variants even the most common SNP in PARP-1 gene (Val762Ala). However, two novel alterations in exon 21 were found to be associated with increased risk of CRC. The variants identified as (1) Lys933Asn [p-value 0.0318] and (2) Lys945Asn [p-value 0.0257]. Our results suggest that PARP-1 Lys933Asn and Lys945Asn alterations could be associated with increased risk of CRC in the Saudi population. -
Jung, Sang Hyuk;Gombojav, Bayasgalan;Park, Eun-Cheol;Nam, Chung Mo;Ohrr, Heechoul;Won, Jong Uk 3675
We assessed the association between frequency of heavy binge drinking and mortality from oropharynx and esophagus cancer after controlling for the total volume of alcohol intake among Korean men. The cohort comprised 2,677 male residents in Kangwha County, aged 55 or older in March 1985, for their upper digestive tract cancer mortality for 20.8 years up to December 31, 2005. For daily binge drinkers versus non-drinkers, the hazard ratios (95% Cls) for mortality were 4.82 (1.36, 17.1) and 6.75 (1.45, 31.4) for oropharyngeal and esophageal cancers, respectively. Even after adjusting for the volume of alcohol intake, we found the hazard ratios for frequency of binge drinking and mortality of oropharyngeal or esophageal cancer to not change appreciably: the hazard ratios were 4.90 (1.00, 27.0) and 7.17 (1.02, 50.6), respectively. For esophageal cancer, there was a strong dose-response relationship. The frequency of heavy binge drinking and not just the volume of alcohol intake may increase the risk of mortality from upper digestive tract cancer, particularly esophageal cancer in Korean men. These findings need to be confirmed in further studies with a larger sample size. -
Yin, Yan;Wang, Rong-Rong;Wang, Yan;Wang, Jian-Jun;Xu, Gen-Xing 3681
In this study, we demonstrated selenium (Se) accumulation in Bifidobacterium longum strain (B. longum) and evaluated the effect of Se-enriched B. longum (Se-B. longum) on tumor growth and immune function in tumor-bearing mice. Analysis using high-performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS) revealed that more than 99% of Se in Se-B. longum was organic, the main component of which was selenomethionine (SeMet). In the in vivo experiments, tumor-bearing mice (n=8) were orally administrated with different doses of Se-B. longum alone or combined with cyclophosphamide (CTX). The results showed that the middle and high dose of Se-B. longum significantly inhibited tumor growth. When Se-B. longum and CTX were combined, the antitumor effect was significantly enhanced and the survival time of tumor-bearing mice (n=12) was prolonged. Furthermore, compared with CTX alone, the combination of Se-B. longum and CTX stimulated the activity of natural killer (NK) cells and T lymphocytes, increasing the levels of interleukin-2 (IL-2) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$ ), and the leukocyte count of H22 tumor-bearing mice (n=12). -
Wang, Hui-Yu;Shen, Jie;Jiang, Chun-Ping;Liu, Bao-Rui 3687
MicroRNA 200c is a microRNA 200 family member that plays an important role in regulation of the epithelial-to-mesenchymal transition (EMT). The prognostic value of microRNA 200c in solid tumors remains controversial because of inconsistent data. Here, we report a meta-analysis of the association of microRNA 200c expression and survival in patients with solid tumors. Pubmed was searched up to November 2013 for studies investigating microRNA 200c expression and overall survival (OS) in solid tumors. Hazard ratios (HRs) with 95% confidence intervals (CIs) for OS were extracted from each study. Pooled HR and CIs were calculated using the Mantel-Haenszel fixed-effects models. A total of five studies evaluating colorectal cancer, gastric cancer, ovarian cancer, pancreatic cancer and endometrial cancer were included in the analysis. Data were divided into tissue microRNA 200c expression group and serum microRNA 200c expression group. The combined HRs [95%CIs] estimated for OS were 0.62 [0.42-0.91] and 2.16 [1.32-3.52] respectively. Low expression of microRNA 200c in tumor tissue and high expression of microRNA 200c in serum are associated with worse survival in solid tumors. Further study is needed to elucidate this contradiction. -
Background: Published studies on the association between the Ras Association Domain Family 1 isoform A (RASSF1A) Ala133Ser polymorphism and cancer susceptibility have yielded conflicting results. Thus, a meta-analysis was here performed to assess the possible association. Materials and Methods: All eligible case-control studies published up to November 2013 on the association between RASSF1A Ala133Ser polymorphism and cancer susceptibility were identified by searching PubMed, Web of Science, Science Direct and hand search. Bothfixed-effect and random-effect models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs) by using the Comprehensive Meta-Analysis software version 2.2. Results: A total of 10 studies including 4,572 cancer cases and 4,320 controls were included in the meta-analysis. Overall, significantly increased cancer risk was associated with the variant Ser133 when all studies were pooled (Ser vs Ala: OR=1.51, 95% CI=1.08-2.12,
$P_{heterogeneity}{\leq}0.001$ ; Ser/Ser+Ala/Ser vs Ala/Ala: OR=1.55, 95% CI=1.08-2.22,$P_{heterogeneity}{\leq}0.001$ ). Moreover, in subgroup analyses by cancer types, a significant association between RASSF1A Ala133Ser polymorphism and lung cancer risk was found (Ser vs Ala: OR=2.27, 95% CI=1.29-4.02,$P_{heterogeneity}$ =0.61; Ser/Ser+Ala/Ser vs Ala/Ala: OR=2.42, 95% CI=1.33-4.42,$P_{heterogeneity}=0.75$ ). In addition, in subgroup analyses by ethnicity, it was found that the RASSF1A Ala133Ser polymorphism was associated with overall cancer risk in Asians (Ser vs Ala: OR=1.37, 95% CI=1.06-1.77,$P_{heterogeneity}=0.06$ ) and Caucasians (Ser/Ser+Ala/Ser vs Ala/Ala: OR=2.21, 95% CI=1.01-4.82,$P_{heterogeneity}{\leq}0.001$ ). Conclusions: This meta-analysis suggests, for the first time, that RASSF1A Ala133Ser polymorphism may contribute to cancer susceptibility, especially for lung cancer. Besides, additional well-designed studies with larger sample size focusing on different ethnicities and cancer types are needed to confirm these findings. -
Yilmazel, Gulay;Duman, Nuriye Buyukkayaci 3699
Background: This study aimed to determine knowledge, attitudes and believes about cervical cancer and human papilloma virus (HPV) vaccination with related factors in Turkish university students. Materials and Methods: This descriptive and cross sectional study was conducted between June-July 2013 in Hitit University located in Corum, a rural area to the East of Ankara. The population consisted of 550 university students who were training in first and last year from Faculties of Economics, Theology and Health. We reached 463 volunteer students without selection. The study of data was collected with a 44 item questionaire covering socio-demographic features, knowledge, attitudes and beliefs about cervical cancer, HPV and vaccination. Also for this study ethic committee report was taken from Bozok University. Data were evaluated with the SPSS 17.0 programme using the Ki kare test with P<0.05 accepted as statistically significant. Results: It was seen that there was a statistically significant variation between classrooms and departments of students with knowledge about cervical cancer and human papilloma virus and vaccine (p<0.001; p<0.01; p<0.05). Also we found low attitudes to thinking about taking HPV vaccination of girls and their children in the future. Conclusions: In light of the study findings; it was concluded that knowledge levels, beliefs and attitudes of the university students about cervical cancer, HPV infection and HPV vaccination were low. -
Deng, Qi-Wen;He, Bang-Shun;Pan, Yu-Qin;Sun, Hui-Ling;Xu, Ye-Qiong;Gao, Tian-Yi;Li, Rui;Song, Guo-Qi;Wang, Shu-Kui 3705
E-Cadherin (CDH1) genetic variations may be involved in invasion and metastasis of various cancers by altering gene transcriptional activity of epithelial cells. However, published studies on the association of CDH1 gene polymorphisms and cancer risk remain contradictory, owing to differences in living habits and genetic backgrounds. To derive a more better and comprehensive conclusion, the present meta-analysis was performed including 57 eligible studies of the association between polymorphisms of CDH1 gene promoter -160 C>A, -347 G>GA and 3'-UTR +54 C>T and cancer risk. Results showed that these three polymorphisms of CDH1 were significantly associated with cancer risk. For -160 C>A polymorphism, -160A allele carriers (CA and CA+AA) had an increased risk of cancer compared with the homozygotes (CC), and the similar result was discovered for the -160A allele in the overall analyses. In the subgroup analyses, obvious elevated risk was found with -160A allele carriers (AA, CA, CA+AA and A allele) for prostate cancer, while a decreased colorectal cancer risk was shown with the AA genotype. For the -347 G>GA polymorphism, the GAGA genotype was associated with increased cancer risk in the overall analysis with homozygous and recessive models. In addition, results of subgroup analysis indicated that the elevated risks were observed in colorectal cancer and Asian descendants. For +54 C>T polymorphism, a decreased risk of cancer was found in heterozygous, dominant and allele models. Moreover, +54T allele carriers (CT, CT+TT genotype and T allele) showed a potential protective factor in gastric cancer and Asian descendants. -
Yan, Jun-Hong;Pan, Lei;Zhang, Xiao-Min;Sun, Cui-Xiang;Cui, Guang-He 3715
Background: It is controversial whether Tai Chi (TC) benefits breast cancer survivors (BCS) on quality of life (QoL). We therefore undertook a meta-analysis to assess this question. Materials and Methods: A computerized search through electronic databases was performed to identify relevant randomized controlled trials (RCTs). The primary outcome was QoL, while secondary outcomes included body mass index (BMI), bone mineral density (BMD), and muscle strength. Results: Five RCTs involving 407 patients were included in the meta-analysis. The pooled standardized mean differences were 0.10 (95% confidence interval (CI): -0.35-0.54) for physical well-being, 0.03 (95%CI: -0.18-0.25) for social/family well-being, 0.24 (95%CI: 0.02-0.45) for emotional well-being, 0.23 (95%CI: -0.03-0.49) for functional well-being, and 0.09 (95%CI: -0.19-0.36) for additional concerns. TC failed to improve BMI, BMD, and muscle strength. Conclusions: There is currently lack of sufficient evidence to support TC improving QoL and other important clinical endpoints. -
Sharma, Jagannath Dev;Kalit, Manoj;Nirmolia, Tulika;Saikia, Sidhartha Protim;Sharma, Arpita;Barman, Debanjana 3721
Background: Cancer is becoming the most important public health burden around the globe. As per the GLOBOCAN 2008 estimates, about 12.7 million cancer cases and 7.6 million cancer deaths were estimated to have occurred in 2008. The burden of cancer cases for India in the year 2020 is calculated to be 1,148,757 (male 534,353; female 614,404) compared to 979,786 in 2010. The pattern of cancer incidence is varying among geographical regions, esophageal cancer for example being high in China, lung cancer in USA, and gallbladder cancer in Chile. The question remains why? Is it due to the diversity in genome pool, food habits, risk factor association and role of genetic susceptibility or some other factors associated with it? In India, the North East (NE)-India region is seeing a marked increase in cancer incidence and deaths, with a very different cancer incidence pattern compared to mainland India. The genome pool of the region is also quite distinct from the rest of India. Northeastern tribes are quite distinct from other groups; they are more closely related to East Asians than to other Indians. In this paper an attempt was made to see whether there is any similarity among the pattern of cancer incidence cases for different sites of NE-India region to South or East-Asia. Materials and Methods: Principal Component Analysis (PCA), Hierarchical Cluster Analysis (HCA), Pearson Correlation coefficient test was assessed to evaluate the linkage of North-East India region to other regions. A p value <0.05 was considered as statistically significant. Results: The results clearly shows that there are similarities in occurrence of cancer incidence patterns for various cancer sites of NE-India with South and East-Asian regions, which may lead to the conclusion that there might be a genetic linkage between these regions. -
Al-Fatlawi, Atheer Abbas;Al-Fatlawi, Anees Abbas;Irshad, Md.;Zafaryab, Md.;Alam Rizvi, M. Moshahid;Ahmad, Ayaz 3731
Phytic acid (PA) has been reported to have positive nutritional benefits and prevent cancer formation. This study investigated the anticancer activity of rice bran PA against hepatocellular carcinoma (HepG2) cells. Cytotoxicty of PA (0.5 to 4mM) was examined by MTT and LDH assays after 24 and 48h treatment. Apoptotic activity was evaluated by expression analysis of apoptosis-regulatory genes [i.e. p53, Bcl-2, Bax, Caspase-3 and -9] by reverse transcriptase-PCR and DNA fragmentation assay. The results showed antioxidant activity of PA in Fe3+ reducing power assay ($p{\leq}0.03$ ). PA inhibited the growth of HepG2 cells in a concentration dependent manner ($p{\leq}0.04$ ). After 48h treatment, cell viability was recorded 84.7, 74.4, 65.6, 49.6, 36.0 and 23.8% in MTT assay and 92.6, 77.0%, 66.8%, 51.2, 40.3 and 32.3% in LDH assay at concentrations of 1, 1.5, 2.0, 2.5, 3.0, and 3.5mM, respectively. Hence, treatment of PA for 24h, recorded viability of cells 93.5, 88.6, 55.5, 34.6 and 24.4% in MTT assay and 94.2, 86.1%, 59.7%, 42.3 and 31.6%, in LDH assay at concentrations of 1, 2.2, 3.0, 3.6 and 4.0mM, respectively. PA treated HepG2 cells showed up-regulation of p53, Bax, Caspase-3 and -9, and down-regulation of Bcl-2 gene ($p{\leq}0.01$ ). At the$IC_{50}$ (2.49mM) of PA, the p53, Bax, Caspase-3 and-9 genes were up-regulated by 6.03, 7.37, 19.7 and 14.5 fold respectively. Also, the fragmented genomic DNA in PA treated cells provided evidence of apoptosis. Our study confirmed the biological activity of PA and demonstrated growth inhibition and induction of apoptosis in HepG2 cells with modulation of the expression of apoptosis-regulatory genes. -
Mesci-Haftaci, Simender;Ankarali, Handan;Yavuzcan, Ali;Caglar, Mete 3737
Background: Abnormal uterine bleeding (AUB) is the most important symptom of endometrial hyperplasia and endometrial curettage (EC) is the gold standard diagnostic procedure. We present the results of patients who underwent EC for AUB and the efficacy of progestin administration in those with endometrial hyperplasia. Materials and Methods: A total of 415 female patients who presented to Duzce Public Hospital in 2011-2012 for AUB and who underwent EC were included. We determined the reasons for AUB, and females with hyperplasia were treated with 10 mg/day medroxyprogesterone acetate for 14 days/month or 160 mg/day megestrol acetate continuously for 3 months. We evaluated the efficacy of progestins for periods of three and/or six cycles by repeating EC. A statistical analysis of specific endometrial causes according to age of presentation was conducted using the chi-square test. Results: Among the 415 females (average age, 53.5 years) followed for 6 months, 186 had physiological changes (44.8%), 89 had simple hyperplasia (21.44%), 1 had atypical hyperplasia (0.2%), 6 had (1.44%) complex hyperplasia, 3 had (0.72%) atypical complex hyperplasia, and 5 had adenocarcinoma (1.2%). Regression rates were 72.7-100%, and the optimum results were observed after 6 months of hormonal therapy. Conclusions: The main cause of AUB was physiological change. Progestin therapy resulted in significant regression even in females with atypical hyperplasia. -
Ding, Jie;Li, Xiao-Mao;Liu, Sui-Ling;Zhang, Yu;Li, Tian 3741
Background: Emerging evidence implicates the platelet-derived growth factor-D (PDGF-D) in many types of human solid tumors. We investigated whether PDGF-D plays an important role in endometrial cancer (EC) in relation to clinicopathologic phenotype, angiogenesis, and patient prognosis. Materials and Methods: We analyzed PDGF-D protein expression by Western blotting in twenty-seven human endometrial cancer tissues, and matched normal endometrial controls collected at the third Affiliated hospital of Sun Yat-sen University during 2012-2013 (n=27). Immunohistochemical staining was performed using a human PDGF-D antibody on the endometrial cancer patients collected in the same facility during January 2001 and October 2013 (n=152). Patients were followed from the time of primary surgery in 2001-2013 until death or last follow-up. We correlated the PDGF-D expression levels with clinicopathologic parameters and prognosis in human endometrial cancer patients. Results: Compared with matched normal endometrial cases, PDGF-D was up-regulated in endometrial cancer. Expression of PDGF-D protein, found in 78% of the cases, was associated with nonendometrioid histologic type (p=0.028), FIGO stage III/IV (p=0.039), >50% solid tumor growth (p=0.048), pelvic LN metastasis (p=0.035) and ER and PR negativity (p=0.04 and 0.002). PDGF-D expression was also significantly associated with expression of VEGF-A (p=0.021). In multivariate analysis, PDGF-D expression proved to be an independent prognostic factor in addition to histologic grade and FIGO stage. Patients with high expression levels of PDGF-D had a significantly poorer overall survival rate compared with patients with no expression. Conclusions: PDGF-D expression is frequently up-regulated in endometrial cancer, and is associated with aggressive features and poor prognosis. -
Du, Qiang;Jiang, Lei;Wang, Xiao-Qian;Pan, Wei;She, Fei-Fei;Chen, Yan-Ling 3747
Background: Gallbladder carcinoma (GBC) is the most common carcinoma of the biliary system. Among its research models, orthotopic xenograft models, important research tools, have been rarely reported in the literature however. Aim: To explore establishment of an orthotopic xenograft model and to evaluate the advantage and disadvantage as compared with other models. Materials and Methods: Subcutaneous xenograft and orthotopic xenograft models of gallbladder carcinoma in nude mice were established and compared with human gallbladder carcinomas. Results: For the orthotopic xenograft model and clinical gallbladder carcinomas, the lymph node metastatic rates were 69.2% and 53.3% (p>0.05); ascites generation rates, 38.5% and 11.7%(p<0.05); liver invasive rates, 100% and 61.7%(p<0.05); and lymphatic vessel densities (LVD),$10.4{\pm}3.02$ and$8.77{\pm}2.92$ (p>0.05), respectively. In the subcutaneous xenograft model, no evidence of ascites generation, lymph node metastasis and liver metastasis were found, and its LVD was lower ($4.56{\pm}1.53$ , p<0.05). Conclusions: Compared with the subcutaneous xenograft model, the orthotopic xenograft model better simulates clinical gallbladder carcinoma in terms of metastasis and invasion, which may be attributed to the difference in microenvironment and LVD. -
Wongwatcharanukul, Laead;Promthet, Supannee;Bradshaw, Peter;Jirapornkul, Chananya;Tungsrithong, Naowarat 3753
Background: Cervical cancer is relatively common in Thai women, but the proportion of females receiving Pap smear screening is still low. Objective: The purpose of this cross-sectional study was to study factors related to cervical cancer screening uptake by Hmong hilltribe women in Lomkao District, Phetchabun Province. Materials and Methods: Interview data were collected from 547 of these women aged 30-60 years living in the study area and analyzed using multiple logistic regression. Results: The results showed that 64.9% of the study sample had received screening, and that 47.2% had attended due to a cervical screening campaign. The most common reason given for not receiving screening was lack of time (21.4%). The factors found to be positively associated with uptake (p value <0.05) were as follows: number of years of school attendance (OR=1.56, 95%CI:1.02-2.38), animistic religious beliefs (OR=0.55, 95%CI:0.33-0.91), a previous pregnancy (OR=6.20, 95%CI:1.36-28.35), receipt of information about cervical cancer screening (OR=2.25, 95%CI:1.35-3.76), and perceived risk of developing cervical cancer (OR=1.83, 95%CI:1.25-2.67). Conclusions: To promote the uptake of cervical screening, Hmong hilltribe women need to know more about cervical cancer and cervical cancer screening, and access to screening services should be provided in conjunction with existing everyday services, such as family planning and routine blood pressure monitoring or diabetes services. -
Rathore, Ankita Singh;Goel, Madhu Mati;Makker, Annu;Kumar, Sandeep;Srivastava, Anand Narain 3757
Purpose: The aim of this study was to investigate the prognostic significance of the CD56+NK-TIL count in infiltrating ductal carcinoma (IDC) of breast. Material and Methods: Immunohistochemistry (IHC) was performed using antibodies specific for CD56 on formalin-fixed and paraffin-embedded tissue sections of 175 infiltrating ductal carcinomas (IDC) of breast. Distribution of intratumoral and stromal CD56+NK-TILs was assessed semi-quantitatively. Results: A low intratumoral CD56+count showed significant and inverse associations with tumor grade, stage, and lymph node status, whereas it had significant and direct association with response to treatment indicating good prognosis. These patients had better survival (${\chi}^2$ =4.80, p<0.05) and 0.52 fold lower death rate (HR=0.52, 95% CI=0.28-0.93) as compared to patients with high CD56+ intratumoral count. The association of survival was insignificant with low CD56 stromal count as compared to high CD56 stromal count (${\chi}^2$ =1.60, p>0.05). Conclusion: To conclude, although NK-TIL count appeared as a significant predictor of prognosis, it alone may not be sufficient for predicting the outcome considering the fact that there exists a crosstalk between NK-TILs and the other immune infiltrating TILs. -
Feng, Chen-Chen;Chen, Li-Na;Chen, Mei-Jun;Li, Wan;Jia, Xu;Zhou, Yan-Yan;He, Wei-Ming 3763
Human mammary epithelial cells have different proliferative statuses and demonstrate a close relationship with age and cell proliferation. Research on this topic could help understand the occurrence, progression and prognosis of breast cancer. In this article, using significance analysis of a microarray algorithm, we analyzed gene expression profiles of human mammary epithelial cells of different proliferative statuses and different age groups. The results showed there were significant differences in gene expression in the same proliferation status between elderly and young groups. Three common differentially expressed genes were found to dynamically change with the proliferation status and to be closely related to tumorigenesis. We also found elderly group had less status-related differential genes from actively proliferating status to intermediate status and more statusrelated differential genes from intermediate status than the young group. Finally, functional enrichment analyses allowed evaluation of the detailed roles of these differentially-expressed genes in tumor progression. -
Introduction: MicroRNAs have emerged as post-transcriptional regulators that are critically involved in tumorigenesis. This study was designed to explore the effect of miRNA 133b on the proliferation and expression of TBPL1 in colon cancer cells. Methods: Human colon cancer SW-620 cells and human colon adenocarcinoma HT-29 cells were cultured. MiRNA 133b mimcs, miRNA 133b inhibitors, siRNA for TBPL1 and scrambled control were synthesized and transfected into cells. MiR-133b levels in cells and CRC tumor tissue was measured by real-time PCR. TBPL1 mRNA was detected by RT-PCR. Cell proliferation was studied with MTT assay. Western blotting was applied to detect TBPL1 protein levels. Luciferase assays were conducted using a pGL3-promoter vector cloned with full length of 3'UTR of human TBPL1 or 3'UTR with mutant sequence of miR-133b target site in order to confirm if the putative binding site is responsible for the negative regulation of TBPL1 by miR-133b. Results: Real time PCR results showed that miRNA 133b was lower in CRC tissue than that in adjacent tissue. After miR-133b transfection, its level was elevated till 48h, accompanied by lower proliferation in both SW-620 and HT-29 cells. According to that listed in http://www.targetscan.org, the 3'-UTR of TBPL1 mRNA (NM_004865) contains one putative binding site of miR-133b. This site was confirmed to be responsible for the negative regulation by miR-133b with luciferase assay. Further, Western blotting and immunohistochemistry both indicated a higher TBPL1 protein expression level in CRC tissue. Finally, a siRNA for TBPL1 transfection obviously slowed down the cell proliferation in both SW-620 and HT-29 cells. Conclusion: MiR-133b might act as a tumor suppressor and negatively regulate TBPL1 in CRC.
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Siriaunkgul, Sumalee;Settakorn, Jongkolnee;Sukpan, Kornkanok;Srisomboon, Jatupol;Utaipat, Utaiwan;Lekawanvijit, Suree;Khunamornpong, Surapan 3773
Background: The study was aimed to evaluate the prevalence and genotype distribution of HPV infection in vulvar squamous cell carcinoma (SCC) in northern Thailand and the clinicopathological difference with regard to HPV infection status. Materials and Methods: Formalin-fixed paraffin-embedded tissue samples of vulvar SCC diagnosed between January 2006 and December 2012 were collected. HPV infection was detected by nested polymerase chain reaction (PCR) with primers MY09/11 and GP5+/6+. HPV genotyping was performed using the Linear Array Genotyping Test, followed by type-specific PCR targeting the E6/E7 region of HPV16/18/52 if the Linear Array test was negative. The histologic slides of vulvar lesions and the medical records were reviewed. Results: There were 47 cases of vulvar SCC included in the study (mean patient age$57.9{\pm}13.2$ years). HPV infection was detected in 29 cases (62%), all of which had single HPV infections. HPV16 accounted for 23 (49%). The patients with HPV-positive SCC had a significantly younger mean age than those with HPV-negative tumors (52.7 years vs 66.2 years, p<0.001). There was no significant difference in tumor stage distribution with regard to the status of HPV infection. The presence of vulvar intraepithelial neoplasia (VIN) of usual type (basaloid or warty) was significantly more frequent in HPV-positive cases compared with HPV-negative cases (62% vs 6%, p<0.001), whereas differentiated-type VIN was more common in HPV-negative cases (24% vs 0%, p=0.019). Conclusions: HPV infection was detected in 62% of vulvar SCC in northern Thailand. HPV16 was the predominant genotype similar to the data reported from other regions. HPV-positive SCC occurred in younger patients compared with HPV-negative SCC, and was associated with usual-type VIN. Vaccination against HPV16/18 may potentially prevent almost one half of vulvar SCC in northern Thailand. -
Raju, Kalyani;Punnayanapalya, Shruthi Suresh;Mariyappa, Narayanaswamy;Eshwarappa, Sumathi Mayagondanahalli;Anjaneya, Chandramouli;Kai, Lee Jun 3779
Aims: To study alterations of plasma lipid profiles in carcinoma cervix and to assess significance comparedwith controls in different histological grades and stages. Materials and Methods: Totals of 99 histopathologically diagnosed cases and 35 controls from a tertiary hospital situated in the southern part of India which caters the rural and semi-urban populations were considered for the study. Fasting blood samples were taken to analyze total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoproteins cholesterol (LDL-C), for comparison of cases, grouped according to histological grades and stages, and controls. One way ANOVA was used for multiple group comparisons and the Student's t test (unpaired) for group wise comparisons. For all tests a 'p' value of 0.05 or less was considered as significant. Results: Out of 99 cases, most (n-39) were seen in the 40-49 year age group followed by 60-69 years (n-22). Serum TG significantly differed between cases and controls but without any relation to differentiation grade. The lipid profile parameters in various grades of cervical cancer were not statistically significant. Statistically significant increase of TC and LDL-C values was observed with increase in stage of the disease. Conclusions: The study showed TG is elevated in cervical cancer, and that TC and LDL-C are proportional to the spread of cancer as it increases from stage I to stage IV. An in-depth study of molecular changes in lipid metabolism in cervical cancer patients, enzymes/genes responsible and alterations in LDL receptors is necessary to provide information to decide whether the lipid profile has any diagnostic/prognostic role in cervical cancer. -
Zhao, Chang-Lin;Qian, Guo-Qiang;Chen, Xiao-Yin;Chen, Chao 3785
Purpose: To explore the clinical characteristics of bone metastasis (BM) in a large sample of preliminarily diagnosed nasopharyngeal carcinomas (NPCs). Methods: The sample consisted of 1,031 patients diagnosed with NPC at first visitg clinics between October 1989 and June 2012. Several parameters including metastasis locus, T/N staging, diagnosis, therapy and prognosis of BM were analyzed retrospectively. Results: In 70 patients who had been preliminarily diagnosed with BM, the incidence of BM in N0, N1, N2 and N3 stage was 5.7%, 17.2%, 50.2%, and 25.7%, respectively, while the incidence in T0, T1, T2 and T3 stage was 0%, 23.8%, 47.6% and 28.6% respectively. BM occurred in most common in vertebral column, rib, sternum, ilium and femur. Positive rate of Epstein-Barr virus antibody was 77.6%. The median survival time was 12 months. Conclusion: The incidence of BM in NPC preliminarily diagnosed is about 7% and it is related to N classification but not T classification. -
Interactions between Filamin A and MMP-9 Regulate Proliferation and Invasion in Renal Cell CarcinomaSun, Guo-Gui;Wei, Cui-Da;Jing, Shao-Wu;Hu, Wan-Ning 3789
This study aimed to analyze the expression, clinical significance of filamin A (FLNA) in renal cell carcinoma (RCC) and biological effects in a cell line by regulating FLNA expression. Immunohistochemistry and Western blotting were used to analyze FLNA protein expression in 70 cases of RCC and normal tissues to study the relationship with clinical factors. FLNA lentiviral and empty vectors were transfected into RCC to study the influence of up-regulated expression of FLNA. FLNA siRNA was transiently transfected into ACHN kidney carcinoma cells by a liposome-mediated method and protein was detected by Western blotting. The level of expression was found to be significantly lower in RCC than normal tissues (p<0.05). No correlation was noted with gender, age, tumor size or pathological types (p>0.05), but links with lymph node metastasis, clinic stage and histological grade were noted (p<0.05). Loss of FLNA expression correlated significantly with poor overall survival time by Kaplan-Meier analysis (p<0.05). Results for biological function showed that ACHN cells transfected with FLNA had a lower survival fraction, significant decrease in migration and invasion, higher cell apoptosis, higher percentage of the G0/G1 phases, and lower MMP-9 protein expression compared with ACHN cells untransfected with FLNA (p<0.05). However, renal 786-0 cells transfected with FLNA siRNA had a higher survival fraction, significant increase in migration and invasion, and higher MMP-9 protein expression compared (p<0.05). In conclusion, FLNA expression was decreased in RCC and correlated significantly with lymph node metastasis, clinic stage, histological grade and poor overall survival, suggesting that FLNA may play important roles as a a tumor suppressor in RCC by promoting degradation of MMP-9. -
Rajabpour, Fatemeh Vand;Raoofian, Reza;Youssefian, Leila;Vahidnezhad, Hassan;Shahshahani, Mostafa Mirshams;Fathi, Hamidreza;Noormohammadpour, Pedram;Hesari, Kambiz Kamyab;Hashemzadeh-Chaleshtori, Morteza;Tabrizi, Mina 3797
Background: BMI1, TWIST1 and SNAI2/SLUG have been implicated in aggressive behavior of squamous cell carcinoma (SCC) and melanoma and BMI1 expression could identify subtypes of Merkel cell carcinoma (MCC). However, BMI1, TWIST1 and SNAI2 expression levels in basal cell carcinomas (BCCs) have not been elucidated. We hypothesized BCC could be a good model system to decipher mechanisms which inhibit processes that drive tumor metastasis. The aim of this study was to examine the mRNA expression level of BMI1, TWIST1, and SNAI2 in BCCs. Materials and Methods: Thirty-five fresh non-metastatic BCC tissue samples and seven fresh normal skin tissue samples were evaluated by real-time RT-PCR. Results: BMI1 and TWIST1 demonstrated marked down-regulation (p<0.00l, p=0.00l respectively), but SNAI2 showed no significant change (p=0.12). Conclusions: Previous literature has clearly demonstrated a positive association between BMI1 and TWIST1 expression and metastatic BCC, aggressive SCC and melanoma. Here, we demonstrated a negative association between BMI1 and TWIST1 mRNA expression level and BCC. -
Gunduz, Seyda;Mutlu, Hasan;Uysal, Mukremin;Coskun, Hasan Senol;Bozcuk, Hakan 3801
Background: The prognostic significance of the neutrophil-to-lymphocyte ratio for progression free survival in patients with metastatic renal cell carcinoma is unclear. Materials and Methods: We retrospectively reviewed 45 patients diagnosed with metastatic RCC previously treated with tyrosine kinase inhibitors from two centers, Akdeniz University Hospital and Afyon Kocatepe University. The prognostic value of the pretreatment neutrophil-tolymphocyte ratio, and other clinical and laboratory parameters were assessed by univariate and multivariate analysis. Results: Median progression free survival (PFS) was 13.9 months [95% CI for HR (6.88-20.91)] and overall survival figure of 16.6 months [95% CI for HR (7.23-26.03)] Univariate analysis revealed that PFS was significantly affected by hemoglobin level [p=0.013 (95% CI for HR (0.71-0.96))], eosinophil count [p=0.031 (95% CI for HR (0.20-0.92))], ratio of neutrophil lymphocytes (NLR) [p=0.007 (95% CI for HR (1.47-11.74))] and calcium level [p=0.006 (95% CI for HR (0.15-0.73))]. However, only NLR [p=0.031 (95% CI for HR (1.15-18.1))] and calcium levels [p=0.018 (95% CI for HR (0.20-18.1))] retained significance with multivariate analysis. Median PFS was 23.9 vs 8.6 months in patients with NLR${\leq}2$ vs NLR >2 (Log rank; p= 0.040). Conclusions: This study showed that increased pretreatment NLR is an independent prognostic factor for patients with metastatic RCC using tyrosine kinase inhibitors. -
Floriano-Sanchez, Esau;Rodriguez, Noemi Cardenas;Bandala, Cindy;Coballase-Urrutia, Elvia;Lopez-Cruz, Jaime 3805
Background: In Mexico, breast cancer (BCa) is the leading type of cancer in women. Cytochrome P450 (CYP450) is a superfamily of major oxidative enzymes that metabolize carcinogens and many antineoplastic drugs. In addition, these enzymes have influence on tumor development and tumor response to therapy. In this report, we analyzed the protein expression in patients with BCa and in healthy women. Links with some clinic-pathological characteristic were also assessed. Materials and Methods: Immunohistochemical analyses were conducted on 48 sets of human breast tumors and normal breast tissues enrolled in Hospital Militar de Especialidades de la Mujer y Neonatologia and Hospital Central Militar, respectively, during the time period from 2010 to 2011. Informed consent was obtained from all participants. Statistical analysis was performed using${\chi}^2$ or Fisher exact tests to estimate associations and the Mann Whitney U test for comparison of group means. Results: We found a significant CYP3A4 overexpression in BCa stroma and gland regions in comparison with healthy tissue. A significant association between protein expression with smoking, alcoholism and hormonal contraceptives use was also observed. Additionally, we observed estrogen receptor (ER) and progesterone receptor (PR) positive association in BCa. Conclusions: We suggest that CYP3A4 expression promotes BCa development and can be used in the prediction of tumor response to different treatments. One therapeutic approach may thus be to block CYP3A4 function. -
Chen, Yang;Li, Jie;Guo, Yun;Guo, Xiao-Yun 3811
Background: Colorectal cancer (CRC) is the worldwide disease which causes enormous losses every year. Recent studies suggested that environmental and gene factors might be the etiologies in increasing the risk of morbidity. Nitric oxide synthase 3 (NOS3) gene polymorphisms are said to be associated with CRC risk but the conclusion is still controversial. Materials and Methods: Pubmed and HuGENet databases up to December 2013 were used in this meta-analysis. Three different certain genotypic models were applied, namely dominant (AA+AC versus CC), recessive (AA versus AC+CC), per-allele analysis (A vs C). In addition, information on tumor sites and pathologic stages was collected. The strength of associations was assessed through combining odds ratio (OR) and 95% confidence interval (CI). Results: Finally, five and three studies about the rs1799983 and rs2070744 were covered in the analysis with 2,745 cases and 2,478 controls. Three models were applied, but no significant association was found for NOS3 G894T/rs1799983 (dominant: OR=0.999, 95%CI=0.797-1.253,$I^2$ =63.8%; recessive: OR=0.924, 95%CI=0.589-1.450,$I^2$ =59.3%; allele analysis: OR=0.979, 95%CI=0.788-1.216,$I^2$ =74.9%) and T-786C/rs2070744 (dominant: OR=1.138, 95%CI=0.846-1.530,$I^2$ =67.9%; recessive: OR=0.956, 95%CI=0.708-1.291,$I^2$ =0.0%; allele analysis: OR=1.110, 95%CI=0.865-1.425,$I^2$ =69.4%). The same results were also obtained for tumor sites and pathologic stage subgroups. After further analyzing the NOS3 gene, rs1799983 as the tag- and functional SNP was presented. Conclusions: On the basis of this meta-analysis and the characteristics of the NOS3 gene, we suggested rs1799983 might be a key locus associated with CRC risk. Further prospective studies were needed to make more comprehensive explanation of the associations. -
Yang, Zhen-Hai;Zhou, Chun-Lin;Zhu, Hong;Li, Jiu-Hong;He, Chun-Di 3817
Background: The MDM2 oncogene, a negative regulator of p53, has a functional polymorphism in the promoter region (SNP309) that is associated with multiple kinds of cancers including non-melanoma skin cancer. SNP309 has been shown to associate with accelerated tumor formation by increasing the affinity of the transcriptional activator Sp1. It remains unknown whether there are other factors involved in the regulation of MDM2 transcription through a trans-regulatory mechanism. Methods: In this study, SNP309 was verified to be associated with overexpression of MDM2 in tumor cells. Bioinformatics predicts that the T to G substitution at SNP309 generates a stronger E2F1 binding site, which was confirmed by ChIP and luciferase assays. Results: E2F1 knockdown downregulates the expression of MDM2, which confirms that E2F1 is a functional upstream regulator. Furthermore, tumor cells with the GG genotype exhibited a higher proliferation rate than TT, correlating with cyclin D1 expression. E2F1 depletion significantly inhibits the proliferation capacity and downregulates cyclin D1 expression, especially in GG genotype skin fibroblasts. Notably, E2F1 siRNA effects could be rescued by cyclin D1 overexpression. Conclusion: Taken together, a novel modulator E2F1 was identified as regulating MDM2 expression dependent on SNP309 and further mediates cyclin D1 expression and tumor cell proliferation. E2F1 might act as an important factor for SNP309 serving as a rate-limiting event in carcinogenesis. -
Surgical outcomes of colorectal cancer treatment depend not only on good surgery and tumor biology but also on an optimal perioperative care. The enhanced recovery program (ERP) - a multidisciplinary and multimodal approach, or so called 'fast-track surgery' - has been designed to minimize perioperative and intraoperative stress responses, and to support the recovery of organ function aiming to help patients getting better sooner after surgery. Compared with conventional postoperative care, the enhanced recovery program results in quicker patient recovery, shorter length of hospital stay, faster recovery of gastrointestinal function, and a lower incidence of postoperative complications. Although not firmly established as yet, the enhanced recovery program after surgery could be of oncological benefit in colorectal cancer patients because it can enhance recovery, maintain integrity of the postoperative immune system, increase feasibility of postoperative chemotherapy, and shorten the time interval from surgery to chemotherapy. This commentary summarizes short-term outcomes and potential long-term benefits of enhanced recovery programs in the treatment of colorectal cancer.