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.
KSCI제15권14호
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Pandurangan, Ashok Kumar;Esa, Norhaizan Mohd 5501
Luteolin, 3', 4', 5,7-tetrahydroxyflavone, belongs to a group of naturally occurring compounds called flavonoids that are found widely in the plant kingdom. It possesses many beneficial properties including antioxidant, anti-inflammatory, anti-bacterial, anti-diabetic and anti-proliferative actions. Colorectal cancer (CRC) is a leading cause of cancer related deaths worldwide. Many signaling pathways are deregulated during the progression of colon cancer. In this review we aimed to analyze the protection offered by luteolin on colon cancer. During colon cancer genesis, luteolin known to reduce oxidative stress thereby protects the cell to undergo damage in vivo. Wnt/${\beta}$ -catenin signaling, deregulated during neoplastic development, is modified by luteolin. Hence, luteolin can be considered as a potential drug to treat CRC. -
Felipe, Aledson Vitor;Oliveira, Juliana de;Chang, Paula Yun Joo;Moraes, Andrea Aparecida de Fatima Souza;Silva, Tiago Donizetti da;Tucci-Viegas, Vanina Monique;Forones, Nora Manoukian 5509
Gastric cancer (GC) remains a virtually incurable disease when metastatic and requires early screening tools for detection of early tumor stages. Therefore, finding effective strategies for prevention or recurrence of GC has become a major overall initiative. RNA-interference (RNAi) is an innovative technique that can significantly regulate the expression of oncogenes involved in gastric carcinogenesis, thus constituting a promising epigenetic approach to GC therapy. This review presents recent advances concerning the promising biomolecular mechanism of RNAi for GC treatment. -
Vaisy, Afasaneh;Lotfinejad, Shirin;Zhian, Faegh 5517
Oral contraceptive use is the most common type of contraception. More than 300 million women worldwide take oral contraceptives every day. However, there is a concern about the relationship with the incidence of cancer. This analytical retrospective study aimed to investigate the relationship between the incidence of cervical and breast cancers and oral contraceptive use in 128 Iranian patients with cervical cancer, 235 with breast cancer and equal numbers of controls. Data were collected through interviews with an organized set of questions. Details were also extracted from patient files. Data were analyzed using Student's t-test, chi-square and Fisher's exact tests, and Pearson's correlation analysis. The result revealed correlations between both cervical and breast cancers and history of contraceptive pills use. While cervical cancer significantly correlated with duration of use of pills, breast cancer had significant correlations with the type of oral contraceptive and age at first use. No significant relationships were found between the two types of cancer and age at discontinuation of oral contraceptives, patterns of use, and intervals from the last use. The use of oral contraceptives may triple the incidence of cervical cancer and doubles the incidence of breast cancer. Therefore, performing Pap smears every six months and breast cancer screening are warranted for long-term oral contraceptive users. -
Adakan, Yesim;Taskoparan, Muharrem;Cekin, Ayhan Hilmi;Duman, Adil;Harmandar, Ferda;Taskin, Vildan;Yilmaz, Ustun;Yesil, Bayram 5523
Objective: To evaluate the implementation of screening colonoscopy amongst first-degree relatives (FDRs) of patients with colorectal cancer (CRC) in Turkey. Materials and Methods: A total of 400 first-degree relatives (mean(SD)age: 42.5(12.7) years, 55.5% were male) of 136 CRC patients were included in this cross-sectional questionnaire based survey. Data on demographic characteristics, relationship to patient and family history for malignancy other than the index case were evaluated in the FDRs of patients as were the data on knowledge about and characteristics related to the implementation of screening colonoscopy using a standardized questionnaire form. Results: The mean(SD) age at diagnosis of CRC in the index patients was 60.0(14.0) years, while mean(SD) age of first degree relatives was 42.5(12.7) years. Overall 36.3% of relatives were determined to have knowledge about colonoscopy. Physicians (66.9%) were the major source of information. Screening colonoscopy was recommended to 19.5% (n=78) of patient relatives, while 48.7% (n=38) of individuals participated in colonoscopy procedures, mostly (57.9%) one year after the index diagnosis. Screening colonoscopy revealed normal findings in 25 of 38 (65.8%) cases, while precancerous lesions were detected in 26.3% of screened individuals. In 19.0% of FDRs of patients, there was a detected risk for Lynch syndrome related cancer. Conclusions: In conclusion, our findings revealed that less than 20% of FDRs of patients had received a screening colonoscopy recommendation; only 48.7% participated in the procedure with detection of precancerous lesions in 26.3%. Rise of awareness about screening colonoscopy amongst patients with CRC and first degree relatives of patients and motivation of physicians for targeted screening would improve the participation rate in screening colonoscopy by FDRs of patients with CRC in Turkey. -
Yuan, Yuan;Cai, Hui;Yang, Xiao-Jun;Li, Wei;He, Jin;Guo, Tian-Kang;Chen, Yi-Rong 5529
Background: The aim of this study was to investigate the effect of a c-myc antisense oligodeoxynucleotide and 5-fluorouracil on the expression of c-myc, invasion and proliferation of HEPG-2 liver cancer cells. Materials and Methods: HEPG-2 cells were treated with lipiosome-mediated c-myc ADSON and 5-fluorouracil. The proliferation inhibition rate and invasion were measured by MTT and invasion assay, respectively. Cell apoptosis was detected by flow cytometry and expression of c-myc by RT-PCR and immunohistochemistry. Results: The proliferation inhibition rate was significantly higher in the antisense oligodeoxynucleotide added-5-fluorouracil group than single antisense oligodeoxynucleotide or 5-fluorouracil group (p<0.05). G0/G1 cells in the antisense oligodeoxynucleotide group and S cells in the 5-fluorouracil groups were significantly increased than that in the control group, respectively (P<0.01). The amplification strips of PCR products in 5-FU, ASODN and combination groups were significantly weaker than that in the control group (P<0.01). The percentage of c-myc-protein-positive cells were significantly lower in antisense oligodeoxynucleotide, 5-fluorouracil and combination groups than that in the control group (P<0.01). Conclusions: A liposome-mediated c-myc antisense oligodeoxynucleotide and 5-fluorouracil can inhibit the proliferation and invasion of liver cancer cells by reducing the expression of c-myc. A c-myc antisense oligodeoxynucleotide can increase the sensitivity of liver cancer cells to 5-fluorouracil and decrease the dosage of the agent necessary for efficacy, providing an experimental basis for the clinical therapy of liver cancer. -
Bi, Wei-Wei;Zhang, Wei-Hua;Yin, Gui-Hua;Luo, Hong;Wang, Shou-Qin;Wang, Hongran;Li, Chao;Yan, Wei-Qun;Nie, De-Zhi 5535
Background: To determine the amount of co-expression of IDO and EGFR in breast cancer patients. Materials and Methods:In order to obtain the distribution of co-expression of IDO and EGFR in breast cancer, we tested 110 breast cancer paraffin tissue blocks with immunohistochemical methods. Then we investigated the relationship between the diagnostic and pathologic characteristics (tumor size, lymph node status, histologic grade, the gene expression of ER, PR, HER2, p53, Ki67 and PCNA) with the situation of co-expression of IDO and EGFR by reviewing the medical records of 32 breast cancer patients. Results: Among 110 breast cancers, 32 cases demonstrated IDO and EGFR co-expression (29.1%), IDO and EGFR synchronous co-expression being found in 19.1% and asynchronous in 10.0%. Conclusions: IDO and EGFR were co-expressed in breast cancer, including synchronous and asynchronous co-expression. The results suggest that considering IDO and EGFR as two indicators for breast cancer treatment or prognosis analysis provides a potential option of individual treatment for the portion of breast cancer patients with co-expression of IDO and EGFR. -
Shim, Hee Jin;Kim, Sung Hun;Kang, Bong Joo;Choi, Byung Gil;Kim, Hyeon Sook;Cha, Eun Suk;Song, Byung Joo 5539
Background: To evaluate the location of tumor relapse and imaging modality for detection according to the breast cancer subtype: luminal A, luminal B, HER2 positive luminal B, nonluminal HER2 positive, and triple negative. Materials and Methods: A total of 1244 patients with breast cancer with known estrogen receptor (ER), progesterone receptor (PR), Ki-67 and human epidermal growth factor receptor 2 (HER2), who underwent breast surgery from 2009 to 2012 were analyzed. Patients were classified into the following categories: luminal A (n=458), luminal B (n=241), HER2 positive luminal B (n=227), nonluminal HER2 positive (n=145) and triple negative (n=173). A total of 105 cases of relapse were detected in 102 patients: locoregional recurrence (n=46), recurrence in the contralateral breast (n=28) and distant metastasis (n=31). Comparison of proportions was used to determine the difference between subtypes. Results: Relapse rates by subtypes are as follows: luminal A 23 of 458 (5.02%), luminal B 19 of 241(7.88%), HER2 positive luminal B 15 of 227 (6.61%), nonluminal HER2 postive 19 of 145 (13.10%) and triple negative 29 of 173(16.76%). Luminal A tumors had the lowest rate of recurrence and had significantly lower recurrence rate in comparison with nonluminal HER2 postive (p=0.0017) and triple negative subtypes (p<0.0001). Compared with all other subtypes except nonluminal HER2 positive, triple negative tumors had the highest rate of tumor recurrence (p<0.01). Triple negatives were most likely to develop contralateral recurrence against all subtypes (p<0.05). Detection rate of locoregional and contralateral tumor recurrence were 28.3% on mammography (n=17/60). Conclusions: Luminal A tumors are associated with a low risk of recurrence while triple negative lesions have a high risk. In case of triple negative tumors, the contralateral breast has much more recurrence as compared with all other subtype. In terms of detection rates, breast USG was the best modality for detecting tumor recurrence, compared with other modalities (p<0.05). Subtyping of breast tumors using a molecular gene expression panel can identify patients who have increased risk of recurrence and allow prediction of locations of tumor recurrence for each subtype. -
Seo, Hwa Jeong;Kim, Hye Hyeon;Im, Jeong Soo;Kim, Ju Han 5545
Background: Human biological materials from cancer patients are linked directly with public health issues in medical science research as foundational resources so securing "human biological material" is truly important in bio-industry. However, because South Korea's national R and D project lacks a proper managing system for establishing a national standard for the outputs of certain processes, high-value added human biological material produced by the national R and D project could be lost or neglected. As a result, it is necessary to develop a managing process, which can be started by establishing operating guidelines to handle the output of human biological materials. Materials and Methods: The current law and regulations related to submitting research outcome resources was reviewed, and the process of data 'acquisition' and data 'distribution' from the point of view of big data and health 2.0 was examined in order to arrive at a method for switching paradigms to better utilize human biological materials. Results: For the deposit of biological research resources, the original process was modified and a standard process with relative forms was developed. With deposit forms, research information, researchers, and deposit type are submitted. The checklist's 26 items are provided for publishing. This is a checklist of items that should be addressed in deposit reports. Lastly, XML-based deposit procedure forms were designed and developed to collect data in a structured form, to help researchers distribute their data in an electronic way. Conclusions: Through guidelines included with the plan for profit sharing between depositor and user it is possible to manage the material effectively and safely, so high-quality human biological material can be supplied and utilized by researchers from universities, industry and institutes. Furthermore, this will improve national competitiveness by leading to development in the national bio-science industry. -
Han, Jun;Meng, Qing-Yang;Liu, Xiao;Xi, Qiu-Lei;Zhuang, Qiu-Lin;Wu, Guo-Hao 5551
Background: The prognostic value of human epidermal growth factor receptor-2 (HER-2/neu) for survival of patients with colorectal cancer (CRC) is still ambiguous. We therefore performed a meta-analysis to evaluate its prognostic significance. Materials and Methods: We searched the MEDLINE and EMBASE databases for published literature investigating associations between HER-2/neu status and overall survival of patients with CRC. A meta-analysis was performed using a DerSimonian-Laird model and publication bias was investigated by Begg's and Egger's tests. Subgroup analysis was also conducted according to the study design type, study quality score, cut-off value for HER-2/neu overexpression, publication region, patient number and publication year. Results: A total of 17 eligible studies involving 2,347 patients were identified for this meta-analysis. The combined hazard ratio (HR) was 1.31 (95% confidence interval (CI): 0.96-1.79), suggesting that HER-2/neu overexpression was not significantly associated with overall survival of patients with CRC. However, subgroup analysis revealed that HER-2/neu overexpression had an unfavorable impact on survival when the analysis was restricted to subgroups of study quality score${\leq}5 $ (HR=1.56, 95%CI: 1.17-2.10), Asian patients (HR=1.74, 95%CI: 1.22-2.49), patient number${\leq}106$ (HR=1.57, 95%CI: 1.01-2.44), publication year before 2003 (HR=1.59, 95%CI: 1.02-2.49), and prospectively designed study (HR=3.62, 95%CI: 1.42-9.24). The effect disappeared in subgroups of study quality scores > 5 (HR=0.69, 95%CI: 0.33-1.44), non Asian patients (HR=1.14, 95%CI: 0.77-1.70), patients' number > 106 (HR=1.07, 95%CI: 0.67-1.72), publication year after 2003 (HR=1.13, 95%CI: 0.76-1.69), and retrospectively designed study (HR=1.22, 95%CI: 0.89-1.67). Conclusions: Our meta-analysis suggests that HER-2/neu overexpression might not be a significantly prognostic indicator for patients with CRC. Further studies are required to confirm these results. -
He, Zhen-Yu;Wu, San-Gang;Zhou, Juan;Sun, Jia-Yuan;Li, Feng-Yan;Lin, Qin;Guo, Ling;Lin, Huan-Xin 5557
Background: This study investigated the survival benefit of radiotherapy (RT) of the supra- and infraclavicular lymphatic drainage area in Chinese women with T1-2N1M0 breast cancer receiving mastectomy. Methods: A total of 593 cases were retrospectively reviewed from 1998 to 2007. The relationship between supra- or infraclavicular fossa relapse (SCFR) and post-operative RT at the supra-/infraclavicular lymphatic drainage area was evaluated. Results: The majority of patients (532/593; 89. 8%) received no RT while 61 patients received RT. The median follow-up was 85 months. Among patients without RT, 54 (10. 2%) developed recurrence in the chest wall or ipsilateral SCFR. However, none of the 61 patients who underwent RT demonstrated SCFR. One patient who received RT (1. 6%) experienced recurrence in the chest wall. Univariate analysis revealed that age and molecular subtype (both P < 0. 05) were two prognostic factors related to supraclavicular and infraclavicular fossa relapse-free survival (SFRFS). Multivariate analysis revealed that only Her-2 positive status (P = 0. 011) was an independent predictor of SFRFS. RT had no influence on distant metastasis (P = 0. 328) or overall survival (P = 0. 541). SCFR significantly affected probability of distant metastasis (P < 0. 001) and overall survival (P < 0. 001). Conclusion: Although RT was not significantly associated with SFRFS, postoperative RT was significantly associated with a lower locoregional (i. e., supraclavicular/infraclavicular and chest wall) recurrence rate. SCFR significantly influenced distant metastasis-free survival, which significantly influenced the overall survival of T1-2N1M0 breast cancer patients after mastectomy. Thus, prophylactic RT is recommended in T1-2N1M0 breast cancer patients, especially those who have Her-2 positive lesions. -
Albasri, Abdulkader;Sawaf, Zeinab;Hussainy, Akbar Shah;Alhujaily, Ahmed 5565
Objectives: This study aimed to characterize the histopathological pattern of thyroid lesions among Saudi patients and to highlight the age and gender variations of these lesions as base line data. Materials and Methods: We retrospectively analyzed the data from thyroid specimens received at the Department of Pathology, King Fahad Hospital, Madinah, Saudi Arabia from January 2006 to December 2013. Results: The 292 thyroidectomy specimens received during the study period came from 230 (78.8%) females and 62 (21.2%) males giving a female: male ratio of 3.7:1. Age of the patients ranged from 14 to 95 years with a mean age 39.7 years. Two hundred and eleven (72.3%) cases were found to be non-neoplastic and 81 (27.7%) cases were neoplastic. The non-neoplastic group included: colloid goiter, including both diffuse and nodular goiter (170 cases; 58.2%), nodular hyperplasia (28 cases; 9.6%), Hashimoto/chronic lymphocytic thyroiditis (12 cases; 4.1%), and Grave's disease (1 case; 0.3%). In neoplastic lesions, there were 7 benign tumors and 74 malignant tumors. Among the benign tumors, 5 were follicular adenomas and 2 were Hurthle cell adenomas. Papillary carcinoma was the commonest malignant tumor accounting for 87.8% of all thyroid malignancies, followed by lymphoma, follicular carcinoma and medullary carcinoma. The size of papillary carcinoma was more than 2 cm in 40 cases (76.9%). Conclusions: Non-neoplastic thyroid lesions were more common than neoplastic ones. Colloid goiter was the most common lesion. Follicular adenoma was the commonest benign tumor and papillary carcinoma was the commonest malignant lesion. There appears to be a slightly increased trend of papillary carcinoma diagnosis, most being diagnosed at an advanced stage. -
Khan, Hafiz Mohammad Rafiqullah;Saxena, Anshul;Gabbidon, Kemesha;Ross, Elizabeth;Shrestha, Alice 5571
Background: The ability to predict the survival time of breast cancer patients is important because of the potential high morbidity and mortality associated with the disease. To develop a predictive inference for determining the survival of breast cancer patients, we applied a novel Bayesian method. In this paper, we propose the development of a databased statistical probability model and application of the Bayesian method to predict future survival times for White Hispanic female breast cancer patients, diagnosed in the US during 1973-2009. Materials and Methods: A stratified random sample of White Hispanic female patient survival data was selected from the Surveillance Epidemiology and End Results (SEER) database to derive statistical probability models. Four were considered to identify the best-fit model. We used three standard model-building criteria, which included Akaike Information Criteria (AIC), Bayesian Information Criteria (BIC), and Deviance Information Criteria (DIC) to measure the goodness of fit. Furthermore, the Bayesian method was used to derive future survival inferences for survival times. Results: The highest number of White Hispanic female breast cancer patients in this sample was from New Mexico and the lowest from Hawaii. The mean (SD) age at diagnosis (years) was 58.2 (14.2). The mean (SD) of survival time (months) for White Hispanic females was 72.7 (32.2). We found that the exponentiated Weibull model best fit the survival times compared to other widely known statistical probability models. The predictive inference for future survival times is presented using the Bayesian method. Conclusions: The findings are significant for treatment planning and health-care cost allocation. They should also contribute to further research on breast cancer survival issues. -
Objective: To observe the effects of metastasis-associated tumor gene family 2 (MTA2) depletion on human breast cancer cell proliferation and metastasis. Methods: A short-hairpin RNA targeting MTA2 was chemically synthesized and transfected into a lentivirus to construct Lv-shMTA2 for infection into the MDA-MB231 human breast cancer cell line. At 48 hours after infection cells were harvested and mRNA and protein levels of MTA2 were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting, respectively. Cell viability and metastasis were assessed by CCK-8, wound-healing assay and Transwell assay, respectively. In addition, a xenograft model of human breast cancer was constructed to investigate cancerous cell growth and capacity for metastasis. Results: After infection with Lv-shMTA2, mRNA and protein levels of MTA2 was significantly reduced (p<0.05) and MDA-MB231 cell proliferation and metastasis were inhibited (p<0.05). In addition, mean tumor size was smaller than that in control group nude mice (p<0.05) and numbers of metastatic deposits in lung were lower than in control group mice (p<0.05). Depletion of MTA2 affected MMP-2 and apoptosis-related protein expression. Conclusions: For the first time to our knowledge we showed that MTA2 depletion could significantly inhibit human breast cancer cell growth and metastasis, implying that MTA2 might be involved in the progression of breast cancer. The role of MTA2 in breast cancer growth and metastasis might be linked with regulation of matrix metalloproteinase and apoptosis.
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Wu, Kai;Yang, Liu;Li, Cong;Zhu, Chao-Hui;Wang, Xin;Yao, Yi;Jia, Yu-Jie 5583
Helicobacter pylori (H. pylori) infection induces apoptosis in gastric epithelial cells, and this occurrence may link to gastric carcinogenesis. However, the regulatory mechanism of H. pylori-induced apoptosis is not clear. MicroRNA-146a has been implicated as a key regulator of the immune system. This report describes our discovery of molecular mechanisms of microRNA-146a regulation of apoptosis in human gastric cancer cells. We found that overexpression of microRNA-146a by transfecting microRNA-146a mimics could significantly enhance apoptosis, and this upregulation was triggered by COX-2 inhibition. Furthermore, we found that microRNA-146a density was positively correlated with apoptosis rates in H. pylori-positive gastric cancer tissues and intratumoral microRNA-146a density was negatively correlated with lymph node metastasis among H. pylori-positive gastric cancer patients. Understanding the important roles of microRNA-146a in regulating cell apoptosis in H. pylori infected human gastric cancer cells will contribute to the development of microRNA targeted therapy in the future. -
Shimpo, Kan;Chihara, Takeshi;Kaneko, Takaaki;Beppu, Hidehiko;Wakamatsu, Kazumasa;Shinzato, Masanori;Yukitake, Jun;Sonoda, Shigeru 5587
Aloe-emodin (AE), a natural anthraquinone compound, has been reported to exhibit anticancer activity in various cancer cell lines and anti-inflammatory effects in murine macrophages. In the present study, we investigated the cancer chemopreventive effects of AE in an Apc-deficient Min mouse model. In the first experiment, male Min mice were fed a basal diet or diets containing 5 ppm AE and 10 ppm AE for 12 weeks. The dietary administration of 5 ppm AE significantly reduced the number of colorectal tumors. In a second experiment, we investigated the effects of AE on colitis-related colon carcinogenesis in Min mouse treated with dextran sodium sulfate (DSS). Female Min mice were administered 1% DSS in their drinking water for 7 days. AE was given to mice in their diet at a dose of 5 or 50 ppm for 5 weeks. Feeding with AE significantly reduced the number of colorectal tumors. When proliferation of cells in normal-appearing colonic mucosa was assessed by monoclonal anti-rat Ki-67 antibody (MIB-5) immunohistochemistry in experiments 1 and 2, the AE treatment significantly decreased the mean MIB-5-labeling index. These results suggest that the dietary administration of low-dose AE may have chemopreventive effects against development of colorectal tumors in Min mice, possibly in part by reducing cell proliferation in colorectal mucosa. -
Background: The objective of this study was to determine a diagnostic classification scheme using a decision tree based model. Materials and Methods: The study was conducted as a retrospective case-control study in Imam Khomeini hospital in Tehran during 2001 to 2009. Data, including demographic and clinical-pathological characteristics, were uniformly collected from 624 females, 312 of them were referred with positive diagnosis of breast cancer (cases) and 312 healthy women (controls). The decision tree was implemented to develop a diagnostic classification scheme using CART 6.0 Software. The AUC (area under curve), was measured as the overall performance of diagnostic classification of the decision tree. Results: Five variables as main risk factors of breast cancer and six subgroups as high risk were identified. The results indicated that increasing age, low age at menarche, single and divorced statues, irregular menarche pattern and family history of breast cancer are the important diagnostic factors in Iranian breast cancer patients. The sensitivity and specificity of the analysis were 66% and 86.9% respectively. The high AUC (0.82) also showed an excellent classification and diagnostic performance of the model. Conclusions: Decision tree based model appears to be suitable for identifying risk factors and high or low risk subgroups. It can also assists clinicians in making a decision, since it can identify underlying prognostic relationships and understanding the model is very explicit.
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Objectives: To assess side effects on Cantharidin sodium and Shenmai injection combined with chemotherapy in treating patients with breast cancer postoperatively. Method: Patients with breast cancer receiving postoperative chemotherapy were retrospectively collected, and divided into four groups: group A with cantharidin sodium injection combined with chemotherapy; group B with Shenmai injection combined with chemotherapy; group C with both cantharidin sodium and Shenmai injection combined with chemotherapy; while group D (control group) received chemotherapy alone. All patients were administered docetaxel at a dose of
$75mg/m^2$ on day 1, epirubicin hydrochloride at a dose of$60mg/m^2$ on day 1, and cyclophosphamide at a dose of$500mg/m^2$ on day 1 for 3 cycles (repeated at 21 day intervals). After${\geq}$ three courses of treatment, quality of life and side effects were evaluated. Results: There were a total of 78 patients in this study, and the incidence of leukopenia and gastrointestinal reactions in groups A and B were lower than those in the control group and lowest in group C (p<0.05). Conclusions: Thus cantharidin sodium and Shenmai injection combined with chemotherapy reduce side effects and deserve to be further investigated in randomized clinical control trials. -
Liang, Yi;Chen, Hua;Zhang, Han-Bin;Jin, Yan-Xia;Guo, Hong-Qiang;Chen, Xing-Gui;Sun, Hui 5601
Background: Agrocybe aegerita Lectin (AAL) has been identified to have high affinity for sulfated and${\alpha}2$ -3-linked sialic acid glycoconjugates, especially the sulfated and sialyl TF (Thomsen-Friedenreich) disaccharide. This study was conducted to investigate the clinicopathological and prognostic value of AAL in identifying aberrant glycosylation in colorectal cancer (CRC). Materials and Methods: Glycoconjugate expression in 59 CRC tissues were detected using AAL-histochemistry. Clinicopathological associates of expression were analyzed with chisquare test or Fisher's exact test. Relationships between expression and the various clinicopathological parameters was estimated using Kaplan-Meier analysis and Cox regression models. Results: AAL specific glycoconjugate expression was significantly higher in tumor than corresponding normal tissues (66.1% and 46.1%, respectively, p=0.037), correlating with depth of invasion (p=0.015) and TNM stage (p=0.024). Patients with lower expression levels had a significantly higher survival rate than those with higher expression (p=0.046 by log rank test and p=0.047 by Breslow test for overall survival; p=0.054 by log rank test and P=0.038 by Breslow test for progress free survival). A marginally significant association was found between AAL specific glycoconjugate expression and overall survival by univariate Cox regression analysis (p=0.059). Conclusions: Lower AAL specific glycoconjugate expression is a significant favorable prognostic factor for overall and progress free survival in CRC. This is the first report about the employment of AAL for histochemical analysis of cancer tissues. The binding characteristics of AAL means it has potential to become a powerful tool for the glycan investigation and clinical application. -
Alipour, Sadaf;Jannat, Forouzandeh;Hosseini, Ladan 5607
Introduction: Although continuing education is necessary for practicing nurses, it is very difficult to organize traditional classes because of large numbers of nurses and working shifts. Considering the increasing development of mobile electronic learning, we carried out a study to compare effects of the traditional face to face method with mobile learning delivered as text messages by cell phone. Materials and Methods: Sixty female nurses working in our hospital were randomly divided into class and short message service (SMS) groups. Lessons concerning breast cancer screening were prepared as 54 messages and sent in 17 days for the SMS group, while the class group participated in a class held by a university lecturer of breast and cancer surgery. Pre- and post-tests were undertaken for both groups at the same time; a retention test also was performed one month later. For statistical analysis, the paired T test and the independent sample T test were used with SPSS software version 16; p<0.05 was considered significant. Results: Mean age and mean work experience of participants in class and SMS groups was$35.8{\pm}7.2$ ,$9.8{\pm}6.7$ ,$35.4{\pm}7.3$ , and$11.5{\pm}8.5$ , respectively. There was a significant increase in mean score post-tests (compared with pretests) in both groups (p<0.05). Although a better improvement in scores of retention tests was demonstrated in the SMS group, the mean subtraction value of the post- and pretests as well as retention- and pretests showed no significant difference between the 2 groups (p=0.3 and p =0.2, respectively). Conclusions: Our study shows that teaching via SMS may probably replace traditional face to face teaching for continuing education in working nurses. Larger studies are suggested to confirm this. -
Yadav, Aman;Goel, Sonu;Sharma, Vijay Lakshmi 5611
Context: Tobacco is the single largest cause of preventable death among adults globally, as it is in India. Despite this alarming situation, there is very minimal inclusion of tobacco in formal education systems, including the medical discipline, in India. Aims: The present study analyzed the extent of integration of tobacco control related content in Masters of Public Health (MPH) curricula of various institutes in India. Materials and Methods: This cross-sectional study was conducted during January 2011 to May 2011 in all colleges of the country offering a MPH course. The colleges were enlisted using various internet search engines (Google Scholar, Pubmed, Medline), other published literature and snowball technique. A 50 items semi-structured questionnaire was designed, posted and e-mailed (followed by hard copy) to the Person-In-Charge of the MPH program. Statistical Analysis: Descriptive statistics were used to profile the tobacco control content in respective institutions. All data entry and analysis was conducted using SPSS (version 16) for windows. Results: The duration of the MPH course was two years in all institutes and had accreditation with some affiliated body. Tobacco related diseases were covered under 'non communicable diseases' section by every institute. However, a mere 41.4% of institute's had faculty who had received specialized training in tobacco control. More coverage was given to health risks and effects of smoking as compared to cessation interventions (5 A's), symptoms of withdrawal and pharmacological treatments. Only 25% of institutes were in process of introducing tobacco courses into their curricula. Lack of expertise and administrative barriers were cited as perceived major problems in inclusion of tobacco control in MPH curricula. Conclusions: It can be concluded that tobacco control is not receiving adequate attention in public health curricula in India. There is a need for coordinated efforts in the area of tobacco control so as to reduce morbidity and mortality from tobacco induced diseases. -
Xu, Chuan;Lv, Peng-Hua;Huang, Xin-En;Wang, Shu-Xiang;Sun, Ling;Wang, Fu-An 5617
Objective: To evaluate the prognosis of different ways of drainage for patients with obstructive jaundice caused by hilar cholangiocarcinoma. Materials and Methods: During the period of January 2006- March 2012, percutaneous transhepatic catheter drainage (PTCD)/ percutaneous transhepatic biliary stenting (PTBS) were performed for 89 patients. According to percutaneous transhepatic cholangiography (PTC), external drainage was selected if the region of obstruction could not be passed by guide wire or a metallic stent was inserted if it could. External drainage was the first choice if infection was diagnosed before the procedure, and a metallic stent was inserted in one week after the infection was under control. Selection by new infections, the degree of bilirubin decrease, the change of ALT, the time of recurrence of obstruction, and the survival time of patients as the parameters was conducted to evaluate the methods of different interventional treatments regarding prognosis of patients with hilar obstruction caused by hilar cholangiocarcinoma. Results: PTCD was conducted in 6 patients and PTBS in 7 (p<0.05). Reduction of bilirubin levels and ALT levels was obvious after the procedures (p<0.05). The average survival time with PTCD was 161 days and with PTBS was 243 days (p<0.05). Conclusions: With both drainage procedures for obstructive jaundice caused by hilar cholangiocarcinoma improvement in liver function was obvious. PTBS was found to be better than PTCD for prolonging the patient survival. -
Tian, Fang-Shuo;Shen, Li;Ren, Yang-Wu;Zhang, Yue;Yin, Zhi-Hua;Zhou, Bao-Sen 5621
N-acetyltransferase 2 (NAT2) is a polymorphic enzyme that plays an important role in the metabolism of various potential carcinogens. In recent years, a number of studies have been carried out to investigate the relationship between the rs1799930 and rs1799931 polymorphism in NAT2 and cancer risk in multiple populations for different types of cancer. However, the results were not consistent. Therefore, we performed a meta-analysis to further explore the relationship between NAT2 polymorphism and the risk of cancer. A total of 21 studies involving 15, 450 subjects for rs1799930 and 13, 011 subjects for rs1799931 were included in this meta-analysis. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess strength of associations. We also evaluated the publication bias and performed a sensitivity analysis. Overall, our results showed an apparent significant association between the NAT2 rs1799930 polymorphism and cancer susceptibility in Asians (GA vs. GG: OR=1.22, 95% CI=1.03-1.45; dominant model: OR=1.22, 95% CI=1.03-1.43) and population-based controls (GA vs. GG: OR=1.10, 95% CI=1.01-1.19; dominant model: OR=1.09, 95% CI=1.01-1.18). In contrast, a significant association was observed between the NAT2 rs1799931 G>A polymorphism and decreased cancer susceptibility in overall meta-analysis (AA vs. GG: OR=0.55, 95% CI=0.33-0.93; GA vs. GG: OR=1.00, 95% CI=0.88-1.14; dominant model: OR=0.97, 95% CI=0.86-1.10; recessive model: OR=0.56, 95% CI=0.34-0.94) and the Asian group (AA vs. GG: OR=0.50, 95% CI=0.26-0.94; recessive model, OR=0.50, 95% CI=0.27-0.94). We found that the NAT2 rs1799930 may be a risk factor, while the NAT2 rs1799931 polymorphism is associated with a decreased risk of cancer and is likely a protective factor against cancer development. -
Alaizari, Nader Ahmed;Al-Maweri, Sadeq Ali 5627
Background: Oral cancer presents with high mortality rates, and the likelihood of survival is remarkably superior when detected early. Dental professionals have an important role and responsibility in prevention and early detection of oral cancer. Purpose: The aim of this study was to assess the knowledge, practices and opinions regarding oral cancer among dentists in Yemen. Materials and Methods: A cross-sectional survey was conducted using a self-administered questionnaire involving private and public dental practitioners, working in different governorates in Yemen. Results: Of the 800 dentists surveyed, a total of 221 questionnaires were completed and returned (response rate 27.6%). A vast majority of dentists (96.38%) identified tobacco as the major risk factor for oral cancer, and 82.8% knew that squamous cell carcinoma is the most common form. While 47.1% of the dentists agreed that they were adequately trained in oral cancer screening, the majority (86%) believed that they need further training in oral cancer screening. Conclusions: These results suggest that additional training and continuing educational programs on prevention and early detection of oral cancer for dentists are to be highly recommended. -
Bien, Agnieszka Maria;Korzynska-Pietas, Magdalena;Iwanowicz-Palus, Grazyna Jolanta 5633
Purpose: Our research project aimed at presenting midwifery student self-assessment of performing the role of breast cancer prevention educator. Materials and Methods: Investigations were carried out in 2011 at the Medical University of Lublin in Poland, and Katolieke Hogeschool of Kortrijk in Belgium, after obtaining approval of the ethical committee of Polish Midwives Association (III/EC/2011/PMA). The project involved a total of 155 midwifery students, made up of 95 from Poland, and 60 from Belgium. Relations between opposing characteristics were tested with Chi-square ($x^2$ ) test for independent traits. To assess the dependence relation between the examined variables Pearson's corrected coefficient was used. Data base and statistics were carried out with computer software STATISTICA 9.0 (StatSoftPoland). Conclusions: Student knowledge on prevention against breast cancer was unsatisfactory. The students place of residence determined their self-estimation of personal knowledge of breast cancer prevention and diagnosing methods to assess the incidence of the disease, this knowledge being better with the students of Lublin. Better self-estimation in the students of Lublin of their personal knowledge on factors rising the risk of breast cancer, such as alimentation method, application of oral contraceptives and breast feeding was found than in Belgian students. -
Zhou, Qin;Shen, Ji-Chuan;Liu, Ying-Zhi;Lin, Guo-Zhen;Dong, Hang;Li, Ke 5639
Objective: This study aimed to determine effects of doctor-patient communication on the quality of life among breast cancer survivors in 16 communities in southern China. Methods: Multistage random sampling was to use to recruit 260 females from the Guangzhou Cancer Registry Database who were diagnosed with breast cancer. A questionnaire provided data on the doctor-patient communication (including the doctor's attitude, the patient's participation with the medical decision and information about the disease) and QOL (quality of life), as measured using FACT-B. Univariate analysis, non-conditional logistic regression was used to evaluate the associations between the doctor-patient communication and QOL. Results: Females who received good attitudes from doctors demonstrated higher FACT-B (OR=4.65, 95% CI: 1.68-12.86), social well-being (OR=5.88, 95% CI: 2.16-16.05), emotional well-being (OR=4.77, 95% CI: 1.92-11.88), and functional well-being ((OR=5.26, 95% CI: 1.90-14.52) compared to the females who encountered worse attitudes from their doctor, adjusting for age, education, marriage, employment, family income, years since diagnosis, TNM stage, radiation therapy, chemotherapy and side effects, particularly when the TNM stage was 0-II and the patients exhibited no side effects. Regardless of the length of time after diagnosis, doctors' good attitudes resulted in higher QOL scores. Conclusions: This study demonstrated that the doctor-patient communication has a significant association with the QOL of breast cancer survivors, mainly dependent on the doctors' attitude. Effective intervention is required to develop optimal doctor-patient communication. -
Whether cyclin D1 (CCND1) gene variants increase susceptibility to head and neck cancer (HNC) is undetermined. Therefore, we performed the present meta-analysis to systematically assess any possible association between CCND1 variants (G870A and G1722C) and HNC risk. Seventeen studies for CCND1 G870A and three studies for CCND1 G1722C were included. Overall, CCND1 polymorphisms (G870A and G1722C) had no association with increased HNC risk (p>0.05). In the subgroup analysis by smoking status, significantly increased HNC risk was found among smokers under allele contrast, homozygous comparison and recessive models (p<0.05), smoking carriers of A allele and AA genotype appearing at elevated risk. In conclusion, while there was overall a lack of any association between CCND1 polymorphisms (G870A and G1722C) and HNC risk, smokers carrying the A allele and AA genotype of the CCND1 G870A polymorphism may be susceptible to HNC development.
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Krusun, Srichai;Pesee, Montien;Supakalin, Narudom;Thamronganantasakul, Komsan;Supaadirek, Chunsri;Padoongcharoen, Prawat 5653
Background: To evaluate factors which effect treatment interruption during concurrent chemoradiotherapy (CCRT) and overall survival in patients with uterine cervical cancer stage IB2-IVA in Srinagarind Hospital. Materials and Methods: Between January 2006 and December 2007, 107 patients with stage IB2-IVA as FIGO staging, 2000, were treated with CCRT in Srinagarind Hospital. Factors which caused treatment interruptions and impacted on overall survival were reviewed and analyzed. Results: Twenty of 107 patients had treatment interruption during CCRT in patients with uterine cervical cancer stage IB2-IVA in Srinagarind Hospital. The causes of treatment interruption were as follows: hematologic toxicity was found in 16 of 20 cases, 12 cases with grade 2 and 4 cases with grade 3; three of 20 cases had gastrointestinal toxicities, 1 case with grade 2 and 2 cases with grade 3; one case had grade 3 skin toxicity. The mean total treatment time of the uninterrupted and interrupted groups were significantly different (78.98 days vs 161.80 days, p <0.001). The patients who could tolerate${\geq}5$ cycles of cisplatin administration had significantly higher mean white blood counts (WBC) ($9,769cells/mm^3$ vs$7,141cells/mm^3$ , p=0.02). The mean initial hemoglobin (Hb) in the uninterrupted group was significantly higher than the interrupted group (11.5 mg% vs 10.3 mg%, p=0.03). Other factors including age, KPS, initial platelets, initial serum creatinine levels showed no statistical significance. The 3-year overall survival of the uninterrupted group was better than in the interrupted group (78.6% vs 55.0%, p=0.03). Conclusions: The initial Hb and WBC levels were significantly correlated with treatment interruption during CCRT in patients with uterine cervical cancer. The 3-year overall survival of the uninterrupted group was significantly better than interrupted group. These factors may then be used indirectly to predict the outcomes of treatment. -
Goh, Teik Beng;Yian, Koh Rhun;Mordi, Mohd Nizam;Mansor, Sharif Mahsufi 5659
Background: To investigate the antioxidant value and anticancer functions of mitragynine (MTG) and its silane-reduced analogues (SRM) in vitro. Materials and Methods: MTG and SRM was analyzed for their reducing power ability, ABTS radical inhibition and 1,1-diphenyl-2-picryl hydrazylfree radicals scavenging activities. Furthermore, the antiproliferation efficacy was evaluated using MTT assay on K 562 and HCT116 cancer cell lines versus NIH/3T3 and CCD18-Co normal cell lines respectively. Results: SRM and MTG demonstrate moderate antioxidant value with ABTS assay (Trolox equivalent antioxidant capacity (TEAC):$2.25{\pm}0.02$ mmol trolox / mmol and$1.96{\pm}0.04$ mmol trolox / mmol respectively) and DPPH ($IC_{50}=3.75{\pm}0.04mg/mL$ and$IC_{50}=2.28{\pm}0.02mg/mL$ respectively). Both MTG and SRM demonstrate equal potency ($IC_{50}=25.20{\pm}1.53$ and$IC_{50}=22.19{\pm}1.06$ respectively) towards K 562 cell lines, comparable to control, betulinic acid (BA) ($IC_{50}24.40{\pm}1.26$ ). Both compounds showed concentration-dependent cytototoxicity effects and exert profound antiproliferative efficacy at concentration >$100{\mu}M$ towards HCT 116 and K 562 cancer cell lines, comparable to those of BA and 5-FU (5-Fluorouracil). Furthermore, both MTG and SRM exhibit high selectivity towards HCT 116 cell lines with selective indexes of 3.14 and 2.93 respectively compared to 5-FU (SI=0.60). Conclusions: These findings revealed that the medicinal and nutitional values of mitragynine obtained from ketum leaves that growth in tropical forest of Southeast Asia and its analogues does not limited to analgesic properties but could be promising antioxidant and anticancer or chemopreventive compounds. -
Bai, Li-Xia;Ding, Ling;Jiang, Shi-Wen;Kang, Hui-Jie;Gao, Chen-Fei;Chen, Chen;Zhou, Qin;Wang, Jin-Tao 5667
Folate receptor alpha ($FR{\alpha}$ ) mediates folate uptake by endocytosis, and while folate is essential to DNA methylation and synthesis and may have an important role in proliferating cells.$FR{\alpha}$ is known to be expressed in rapidly proliferating cells, including many cancer cell lines, but there has been no systematic assessment of expression in cervical cancer cell lines. The aim of the present study was to evaluate the effects of$FR{\alpha}$ on proliferation and apoptosis of cervical cells and correlation mechanism. In this study, we investigated the biological function of$FR{\alpha}$ in Hela cells using RNA interference. Cell proliferation was evaluated by Cell Counting Kit-8 (CCK8) assay, while cell cycling and apoptosis were assessed by flow cytometry, mRNA levels by real time-PCR and protein levels of$FR{\alpha}$ , c-Fos and c-Jun by Western blotting. The results revealed that$FR{\alpha}$ was highly expressed in Hela cells and its silencing with a small interfering RNA (siRNA) inhibited cell proliferation and induced cell apoptosis, arresting the cell cycle in G0/G1 stages while decreasing the proportion in S and G2/M stages, and suppressed the expression levels of c-Fos and c-Jun. In conclusion, the results of this study indicated that$FR{\alpha}$ down-regulation might be capable of suppressing cervical cancer cell proliferation and promoting apoptosis. It suggested that$FR{\alpha}$ might be a novel therapeutic target for cervical cancer. -
Bu, Zhi-Bin;Ye, Meng;Cheng, Yun;Wu, Wan-Zhen 5673
Background: Previous published data on the association between CYP1A2 rs762551, rs2069514, rs2069526, and rs2470890 polymorphisms and lung cancer risk have not allowed a definite conclusion. The present meta-analysis of the literature was performed to derive a more precise estimation of the relationship. Materials and Methods: 8 publications covering 23 studies were selected for this meta-analysis, including 1,665 cases and 2,383 controls for CYP1A2 rs762551 (from 8 studies), 1,456 cases and 1,792 controls for CYP1A2 rs2069514 (from 7 studies), 657 cases and 984 controls for CYP1A2 rs2069526 (from 5 studies) and 691 cases and 968 controls for CYP1A2 rs2470890 (from 3 studies). Results: When all the eligible studies were pooled into the meta-analysis for the CYP1A2 rs762551 polymorphism, significantly increased lung cancer risk was observed in the dominant model (OR=1.21, 95 % CI=1.00-1.46). In the subgroup analysis by ethnicity, significantly increased risk of lung cancer was observed in Caucasians (dominant model: OR=1.29, 95%CI=1.11-1.51; recessive model: OR=1.33, 95%CI=1.01-1.75; additive model: OR=1.49, 95%CI=1.12-1.98). There was no evidence of significant association between lung cancer risk and CYP1A2 rs2069514, s2470890, and rs2069526 polymorphisms. Conclusions: In summary, this meta-analysis indicates that the CYP1A2 rs762551 polymorphism is linked to an increased lung cancer risk in Caucasians. Moreover, our work also points out the importance of new studies for rs2069514 associations in lung cancer, where at least some of the covariates responsible for heterogeneity could be controlled, to obtain a more conclusive understanding about the function of the rs2069514 polymorphism in lung cancer development. -
Takiar, Ramnath;Krishnan, Sathish Kumar;Shah, Varsha Premchandbhai 5681
Objective: Prevalence is a statistic of primary interest in public health. In the absence of good follow-up facilities, it is often difficult to assess the complete prevalence of cancer for a given registry area. An attempt is made to arrive at the complete prevalence including limited duration prevalence with respect of selected sites of cancer for India by fitting appropriate models to 1, 3 and 5 year cancer survival data available for selected registries of India. Methodology: Cancer survival data, available for the registries of Bhopal, Chennai, Karunagappally, and Mumbai was pooled to generate survival for the selected cancer sites. With the available data on survival for 1, 3 and 5 years, a model was fitted and the survival curve was extended beyond 5 years (up to 30 years) for each of the selected sites. This helped in generation of survival proportions by single year and thereby survival of cancer cases. With the help of estimated survived cases available year wise and the incidence, the prevalence figures were arrived for selected cancer sites and for selected periods. In our previous paper, we have dealt with the cancer sites of breast, cervix, ovary, lung, stomach and mouth (Takiar and Jayant, 2013). Results: The prevalence to incidence ratio (PI ratio) was calculated for 30 years duration for all the selected cancer sites using the model approach showing that from the knowledge of incidence and P/I ratio, the prevalence can be calculated. The validity of the approach was shown in our previous paper (Takiar and Jayant, 2013). The P/I ratios for the cancer sites of lip, tongue, oral cavity, hypopharynx, oesophagus, larynx, nhl, colon, prostate, lymphoid leukemia, myeloid leukemia were observed to be 10.26, 4.15, 5.89, 2.81, 1.87, 5.43, 5.48, 5.24, 4.61, 3.42 and 2.65, respectively. Conclusion: Cancer prevalence can be readily estimated with use of survival and incidence data. -
Kim, Kyoungwoo;Yoo, Taiwoo;Kim, Yeonju;Choi, Ji-Ho;Myung, Seung-Kwon;Park, Sang-Min;Hong, Yun-Chul;Cho, Belong;Park, Sue K.;Yoo, Keun-Young 5685
Background: It is well known that smoking is a preventable factor for all-cause mortality; however, it is still questionable how many years after smoking cessation that people will have reduced risk for mortality, in particular in those with a high interest in their own health. We aimed to examine the association between time since quitting smoking and total mortality among past-smokers relative to current smokers. Materials and Methods: We enrolled 36,446 health examinees that voluntarily taken with diverse health check-up packages of high cost burden in 1995-2003 and followed them till death by 2004. The history of cigarette smoking consumption was collected using a self-administrative questionnaire at the first visit time. Mortality risk by smoking cessation years was analyzed using Cox's proportional hazard model. Results: Compared to non-smokers, male smokers over 15 pack-years had higher risk for total mortality (HR=1.60, 95%CI 1.23-2.14). The mortality risk in female smokers with same pack-years was more pronounced than that in male smokers (HR=2.83, 95%CI 1.17-7.04) despite a small number of cases. Compared to current smokers, a decrease of total mortality was observed among those who ceased smoking, and inverse dose-response was found with years after cessation: RR 0.98 (95%CI, 0.64-1.41) (<2 yrs), 0.60 (95%CI, 0.43-0.83) (3-9 yrs), and 0.58 (95%CI, 0.43-0.79) (${\geq}10$ yrs). Conclusions: A reduced risk of total mortality was observed after 3 years of smoking cessation. Our findings suggest that at least 3 years of smoking cessation may contribute to reduce premature mortality among Asian men. -
Wang, Wei-Lan;Tang, Zhi-Hui;Xie, Ting-Ting;Xiao, Bing-Kun;Zhang, Xin-Yu;Guo, Dai-Hong;Wang, Dong-Xiao;Pei, Fei;Si, Hai-Yan;Zhu, Man 5691
Background: Many clinical trials have been conducted to evaluate sorafenib for the treatment of advanced NSCLC, but the results for efficacy have been inconsistent. The aim of this study was to evaluate the efficacy and safety of sorafenib in patients with advanced NSCLC in more detail by meta-analysis. Methods: This meta-analysis of randomized controlled trials (RCTs) was performed after searching PubMed, EMBASE, ASCO Abstracts, ESMO Abstracts, and the proceedings of major conferences for relevant clinical trials. Two reviewers independently assessed the quality of the trials. Outcomes analysis were disease control rate (DCR), progression- free survival (PFS), overall survival (OS) with 95% confidence intervals (CI) and major toxicity. Subgroup analysis was conducted according to sorafenib monotherapy, in combination with chemotherapy or EGFR-TKI to investigate the preferred therapy strategy. Results: Results reported from 6 RCTs involving 2, 748 patients were included in the analysis. Compared to sorafenib-free group, SBT was not associated with higher DCR (RR 1.31 (0.96- 1.79), p=0.09), PFS (HR 0.82 (0.66-1.02), p=0.07) and OS (HR 1.01 (0.92-1.12), p=0.77). In terms of subgroup results, sorafenib monotherapy was associated with significant superior DCR and longer PFS, but failed to show advantage with regard to OS. Grade 3 or greater sorafenib-related adverse events included fatigue, hypertension, diarrhea, oral mucositis, rash and HFSR. Conclusions: SBT was revealed to yield no improvement in DCR, PFS and OS. However, sorafenib as monotherapy showed some activity in NSCLC. Further evaluation may be considered in subsets of patients who may benefit from this treatment. Sorafenib combined inhibition therapy should be limited unless the choice of platinum-doublet regimen, administration sequence or identification of predictive biomarkers are considered to receive better anti-tumor activity and prevention of resistance mechanisms. -
Wang, Li-Jie;Liu, Xiu-Ju;Guan, Yan;Zhang, Chu-Feng;Wang, Peng;Li, Yan;Guo, Qi-Sen 5697
Objective: To investigate the optimal timing of radiotherapy with alternating/sequential radio-chemotherapy for limited-stage small cell lung cancer (LS-SCLC). Methods: 91 patients with LS-SCLC were retrospectively analyzed and divided into two groups according to the number of chemotherapy cycles before radiotherapy. If the patient received radiotherapy after 3 cycles or fewer cycles of chemotherapy, classification was into the early group, if not, into the late group. All patients received 6 cycles of standard chemotherapy (EP/EC) and conventional radiotherapy (56 gy~ 60 gy/28 f ~30 f). Results: The response rate (RR) of the early and late groups were 85.7% and 81.6%, respectively, with no significant difference (p>0.05). In contrast, the progression-free survival (PFS) in the early group was better than that in the late group (11.8 months vs 9.86 months), and the difference was significant (p<0.05). There was no significant difference between two groups in adverse reactions, which gastrointestinal irritation and bone marrow suppression being the most common (p>0.05). Conclusions: Radiotherapy after 3 cycles or fewer cycles of chemotherapy does not bring significant benefits for RR of patients with LS-SCLC, but it could significantly prolong their PFS without increase in adverse reactions. -
Altinay, Serdar;Taskın, Umit;Sar, Mehmet;Aydin, Salih;Oktay, Mehmet Faruk 5701
Background: Salivary gland tumours, which account for approximately 3% of head-neck cancers, are a heterogeneous group and thus it is difficult to identify their epidemiological characteristics. The aim of this study is to determine demographic features and histopathologic distribution of parotid neoplasms in a large sample from Turkey. Materials and Methods: This study was conducted retrospectively on 136 parotidectomy materials from operations between May 2009-May 2013. Age, gender, tumor diameter, histopathological diagnosis and surgical margin status were recorded. Results: The benign cases were 112 (82.4%), while the malignancies were 24 (17.6%). The accuracy rate of FNAC was 91%. There were 46 (33.8%) male and 90 (66.2%) female patients. Female/male ratio (M/F=0.5) was two, the Warthin (WT) tumor being more apparent in males (p<0.05). Pleomorphic adenoma (PA) was detected most frequently among benign pathologies at 61.6% (69/112), while the Warthin Tumor (WT) was detected as the second most frequent tumor at 20.5% (23/112). Mucoepidermoid carcinoma (MEC) and carcinoma ex pleomorphic adenoma (Ca ex PA) were detected at equal frequency at 20.8% (5/24) among malign tumors. These were followed by acinic cell carcinoma at 16.7% (4/24). While the surgical margin was positive in ten patients with malignant tumors (41.7%), all of the benign tumors were negative (p<0.01). No significant difference was detected in the age-gender of patients, tumor size and distribution of sites among benign and malignant groups (p>0.05). Conclusions: Pleomorphic adenoma is the most frequently reported benign tumor almost in all global literature. Yet, the distribution of malignant tumors displays geographical differences. Based on these data, we believe that our findings will provide a significant contribution to future epidemiological studies. We think that it will be beneficial to generate awareness on parotid tumors and ensure a fight against smoking as with all head-neck cancers. -
Leon-Hernandez, Saul Renan;Padilla, Eleazar Lara;Algara, Alfredo Cortes;Rodriguez, Noemi Cardenas;Sanchez, Esau Floriano;Cruz, Jaime Lopez;Barradas, Cesar Miguel Mejia;Bandala, Cindy 5709
Background: An association between alcohol/tobacco use and risk of metastasis in breast cancer has been clearly shown. Materials and Methods: The present study explored, in 48 samples of tissue from mammary ductal carcinoma (taken from Mexican women with an average age of$58.2{\pm}10.9$ years), the association of risk of metastasis with the status of hormonal receptors and the c-erbB2 protein (by immunohistochemistry) as well as clinical, histopathological and sociodemographic factors. Results: Of 48 patients, 41.6% (20/48) presented with metastasis, 43.8% were positive for the estrogen receptor (RE+), 31.3% for the progesterone receptor (RP+) and 47.7% for c-erbB2 (c-erbB2+). The following combinations were found: RE+/RP+/c-erbB2+ 8.3%, RE+/RP+ 22.9%, RE+/RP- 20.8%, RE-/RP+ 8.3%, RE-/RP-/c-erbB2- 22.9% and RE-/RP- 47.8%. There were 12 patients who used alcohol/tobacco, of which 91.6% did not present metastasis and 81.9% were RE-/RP-. Compared to the RE-/RP-/c-erbB2+, the RE+/RP+/c-erbB2+ group had a 15-fold greater risk for metastasis (95%CI, 0.9-228.8, p=0.05). The carriers of the double negative hormonal receptors had a 4.7 fold greater probability of being (or having been) smokers or drinkers (95%CI, 1.0-20.4, p = 0.03). Conclusions: There was a clear protective effect of using alcohol and/or tobacco, in the cases included in the present study of mammary ductal carcinoma, associated with double negative hormonal receptors. However, this association could be due to a protective factor not measured (Neyman bias) or to a bias inherent in the rate of hospitalization (Berkson fallacy). This question should be explored in a broad prospective longitudinal study. -
Li, Cai-Li;Wei, Hu-Lai;Chen, Jing;Wang, Bei;Xie, Bei;Fan, Lin-Lan;Li, Lin-Jing 5715
Autophagy is crucial in the maintenance of homeostasis and regenerated energy of mammalian cells. Macroautophagy and chaperone-mediated autophagy(CMA) are the two best-identified pathways. Recent research has found that in normal cells, decline of macroautophagy is appropriately parallel with activation of CMA. However, whether it is also true in cancer cells has been poorly studied. Here we focused on cross-talk and conversion between macroautophagy and CMA in cultured Burkitt lymphoma Raji cells when facing serum deprivation and exposure to a toxic compound, arsenic trioxide. The results showed that both macroautophagy and CMA were activated sequentially instead of simultaneously in starvation-induced Raji cells, and macroautophagy was quickly activated and peaked during the first hours of nutrition deprivation, and then gradually decreased to near baseline. With nutrient deprivation persisted, CMA progressively increased along with the decline of macroautophagy. On the other hand, in arsenic trioxide-treated Raji cells, macroautophagy activity was also significantly increased, but CMA activity was not rapidly enhanced until macroautophagy was inhibited by 3-methyladenine, an inhibitor. Together, we conclude that cancer cells exhibit differential responses to diverse stressor-induced damage by autophagy. The sequential switch of the first-aider macroautophagy to the homeostasis-stabilizer CMA, whether active or passive, might be conducive to the adaption of cancer cells to miscellaneous intracellular or extracellular stressors. These findings must be helpful to understand the characteristics, compensatory mechanisms and answer modes of different autophagic pathways in cancer cells, which might be very important and promising to the development of potential targeting interventions for cancer therapies via regulation of autophagic pathways. -
Guo, Pi;Shen, Shun-Li;Zhang, Qin;Zeng, Fang-Fang;Zhang, Wang-Jian;Hu, Xiao-Min;Zhang, Ding-Mei;Peng, Bao-Gang;Hao, Yuan-Tao 5721
Objectives: To evaluate the performance of clustering methods used in the prognostic assessment of categorical clinical data for hepatocellular carcinoma (HCC) patients in China, and establish a predictable prognostic nomogram for clinical decisions. Materials and Methods: A total of 332 newly diagnosed HCC patients treated with hepatic resection during 2006-2009 were enrolled. Patients were regularly followed up at outpatient clinics. Clustering methods including the Average linkage, k-modes, fuzzy k-modes, PAM, CLARA, protocluster, and ROCK were compared by Monte Carlo simulation, and the optimal method was applied to investigate the clustering pattern of the indices including platelet count, platelet/lymphocyte ratio (PLR) and serum aspartate aminotransferase activity/platelet count ratio index (APRI). Then the clustering variable, age group, tumor size, number of tumor and vascular invasion were studied in a multivariable Cox regression model. A prognostic nomogram was constructed for clinical decisions. Results: The ROCK was best in both the overlapping and non-overlapping cases performed to assess the prognostic value of platelet-based indices. Patients with categorical platelet-based indices significantly split across two clusters, and those with high values, had a high risk of HCC recurrence (hazard ratio [HR] 1.42, 95% CI 1.09-1.86; p<0.01). Tumor size, number of tumor and blood vessel invasion were also associated with high risk of HCC recurrence (all p< 0.01). The nomogram well predicted HCC patient survival at 3 and 5 years. Conclusions: A cluster of platelet-based indices combined with other clinical covariates could be used for prognosis evaluation in HCC. -
Shirazi, Ahmad Soltani;Razi, Taghi;Cheraghi, Fatemeh;Rahim, Fakher;Ehsani, Sara;Davoodi, Mohammad 5729
Background: Cervical cancer is the third most common gynecological cancer and a widespread malignancy in women, accounting for a large proportion of the cancer burden in developing countries. We compared accuracy of MRI staging with clinical staging and also concordance between the two methods for newly diagnosed patients with cervical cancer, using clinical staging as the reference. Materials and Methods: This prospective study was conducted on 27 newly diagnosed patients with cervical cancer from Imam Khomeini hospital from June 2012 to Feb 2014. New cases of cervical cancer with positive PAP test were staged separately with a clinical exam based on the FIGO system by a gynecologist, oncologist and also with MRI by an expert radiologist. Then we compared the predicted stage for each patient with the two methods. Results: Based on clinical staging 9 patients (33%) were observed at stage 1. MRI staging was in coordination with clinical staging in eight of them and for one patient MRI accorded stage 2B (88% concordance). Conclusions: MRI is a reliable noninvasive method with high accuracy for cervical cancer staging. Also presently it is easily obtainable, so we recommend using this technique along with clinical examination for staging cervical cancer patients. We also recommend to radiologists and residents of radiology to get experience with this method of staging. -
Ostadrahimi, Alireza;Ziaei, Jamal Eivazi;Esfahani, Ali;Jafarabadi, Mohammad Asghari;Movassaghpourakbari, Aliakbar;Farrin, Nazila 5733
Background: Breast cancer is the most common female malignancy in the world. Beta glucan can be a hematopoietic and an immune modulator agent in cancer patients. The aim of this trial was to determine the effect of beta glucan on white blood cell counts and serum levels of IL-4 and IL-12 in women with breast cancer undergoing chemotherapy. Materials and Methods: This randomized double-blind placebo-controlled clinical trial was conducted on 30 women with breast carcinoma aged 28-65 years. The eligible participants were randomly assigned to intervention (n=15) or placebo (n=15) groups using a block randomization procedure with matching based on age, course of chemotherapy and menopause status. Patients in the intervention group received two 10-mg capsules of soluble 1-3, 1-6, D-beta glucan daily and the control group receiving placebo during 21 days, the interval between two courses of chemotherapy. White blood cells, neuthrophil, lymphocyte and monocyte counts as well as serum levels of IL-4 and IL-12 were measured at baseline and at the end of the study as primary outcomes of the study. Results: In both groups white blood cell counts decreased after 21 days of the intervention, however in the beta glucan group, WBC was less decreased non significantly than the placebo group. At the end of the study, the change in the serum level of IL-4 in the beta glucan group in comparison with the placebo group was statistically significant (p=0.001). The serum level of IL-12 in the beta glucan group statistically increased (p=0.03) and comparison between two groups at the end of the study was significant after adjusting for baseline values and covariates (p=0.007). Conclusions: The findings suggest that beta glucan can be useful as a complementary or adjuvant therapy and immunomodulary agent in breast cancer patients in combination with cancer therapies, but further studies are needed for confirmation. -
Huang, Gang;Dang, Zhong-Feng;Dang, Ya-Mei;Cai, Wei;Li, Yuan;Chen, Yi-Rong;Xie, Xiao-Dong 5741
Purpose: To study the expression of insulin-like growth factor binding proteins (IGFBPs) in paclitaxel-treated gastric cancer SGC-7901 cells, and to further investigate underlying mechanisms. Materials and Methods: Real time PCR and Western blot assays were applied to detect the mRNA and protein expression of IGFBP-2, -3 and -5 after paclitaxel (10 nM) treatment of SGC-7901 cells. In addition IGFBP-3 expression was silenced by RNA interference to determine effects. Cell viability was determined by MTT assay. Cell cycling and apoptosis were assessed by flow cytometry. Results: Compared to the control group, only IGFBP-3 expression was elevated significantly after paclitaxel (10 nM) treatment (p<0.05). Paclitaxel treatment caused cell cycle arrest and apoptosis via downregulating Bcl-2 expression. However, the effect could be abrogated by IGFBP-3 silencing. Conclusions: IGFBP-3 exhibits anti-apoptotic effects on paclitaxel-treated SGC-7901 cells via elevating Bcl-2 expression. -
Li, Jing;Qiu, Dong-Min;Chen, Shao-Hua;Cao, Su-Ping;Xia, Xue-Lan 5747
Background: Coptisine, an isoquinoline alkaloid extracted from Coptidis rhizoma, has many biological activities such as antidiabetic, antimicrobial and antiviral actions. However, whether coptisine exerts anti-cancer metastasis effects remains unknown. Materials and Methods: Effects of coptisine on highly metastatic human breast cancer cell MDA-MB-231 proliferation were evaluated by trypan blue assay and on cell adhesion, migration and invasion by gelatin adhesion, wound-healing and matrigel invasion chamber assays, respectively. Expression of two matrix metalloproteinases (MMPs), MMP-9, MMP-2 and their specific inhibitors tissue inhibitor of metalloproteinase 1 (TIMP-1) and tissue inhibitor of metalloproteinase 2 (TIMP-2) were analyzed by RT-PCR. Results: Coptisine obviously inhibited adhesion to an ECM-coated substrate, wound healing migration, and invasion through the matrigel in MDA-MB-231 breast cancer cells. RT-PCR revealed that coptisine reduced the expression of the ECM degradation-associated gene MMP-9 at the mRNA level, and the expression of TIMP-1 was upregulated in MDA-MB-231 cells, while the expression of MMP-2 and its specific inhibitor TIMP-2 was not affected. Conclusions: Taken together, our data showed that coptisine suppressed adhesion, migration and invasion of MDA-MB-231 breast cancer cells in vitro, the down-regulation of MMP-9 in combination with the increase of TIMP-1 possibly contributing to the anti-metastatic function. Coptisine might be a potential drug candidate for breast cancer therapy. -
Dilli, Utku Donem;Yildırim, Mustafa;Suren, Dinc;Alikanoglu, Arsenal;Kaya, Vildan;Goktas, Sevil;Yildiz, Mustafa;Sezer, Cem;Gunduz, Seyda 5753
Background: The purpose of this study is to determine whether the IGF1R expression has a prognostic role in non-small cell lung cancer. Materials and Methods: Forty-seven patients histopathologically diagnosed with small cell lung cancer upon bronchoscopic biopsy or resection materials were included in the study. IGF1R expression was examined via immunohistochemical methods. In samples, >10% staining were assessed as positive and${\leq}10%$ as negative. Information about demographic datas and treatments was obtained by retrospective searches of patient files. Results: IGF1R expression was determined as positive in 38 (80.9%) and as negative in 9 (19.1%) patients. There was no significant relation between IGF1R expression and histological sub-type, local invasion, lymph node and metastasis status (p=0.842, p=0.437, 0.064, 0.447, respectively). There was also no correlation with IGF1R expression and survival (p=0.141). Conclusions: There are conflicting results between IGF1R and its prognostic effects in the various studies. It has been claimed in some studies it is not related to prognosis as in our study, and in some studies it has been claimed that it is a good prognostic factor whereas in some studies it has been claimed as being a factor for worse prognosis. We think that IGF1R expression in non-small cell lung carcinoma patients deserves further analysis, because of its potential prognostic and predictive roles. -
Juliana, Norsham;Shahar, Suzana;Chelliah, Kanaga Kumari;Ghazali, Ahmad Rohi;Osman, Fazilah;Sahar, Mohd Azmani 5759
Electrical impedance tomography (EIT) is a potential supplement for mammogram screening. This study aimed to evaluate and feasibility of EIT as opposed to mammography and to determine pain perception with both imaging methods. Women undergoing screening mammography at the Radiology Department of National University of Malaysia Medical Centre were randomly selected for EIT imaging. All women were requested to give a pain score after each imaging session. Two independent raters were chosen to define the image findings of EIT. A total of 164 women in the age range from 40 to 65-year-old participated and were divided into two groups; normal and abnormal. EIT sensitivity and specificity for rater 1 were 69.4% and 63.3, whereas for rater 2 they were 55.3% and 57.0% respectively. The reliability for each rater ranged between good to very good (p<0.05). Quantitative values of EIT showed there were significant differences in all values between groups (ANCOVA, p<0.05). Interestingly, EIT scored a median pain score of$1.51{\pm}0.75$ whereas mammography scored$4.15{\pm}0.87$ (Mann Whitney U test, p<0.05). From these quantitative values, EIT has the potential as a health discriminating index. Its ability to replace image findings from mammography needs further investigation. -
Xiong, Hai-Yu;Ma, Ting-Ting;Wu, Bi-Tao;Lin, Yan;Tu, Zhi-Guang 5767
Background and Aim: B7-H1, a co-inhibitory molecule of the B7 family, is found aberrantly expressed in ovarian cancer cells and infiltrating macrophage/dendritic-like cells, and plays a critical role in immune evasion by ovarian cancer. IL-12, an inducer of Th1 cell development, exerts immunomodulatory effects on ovarian cancer. However, whether IL-12 regulates B7-H1 expression in human ovarian cancer associated-macrophages has not been clarified. Therefore, we investigated the effects of IL-12 on the expression of B7-H1 in ovarian cancer-associated macrophages and possible mechanisms. Methods: PMA induced THP-1-derived macrophages or human monocyte-derived macrophages were treated with recombinant IL-12 (rIL-12) or infected with adenovirus carrying human IL-12 gene (Ad-IL-12-GFP) for 24 h, then cocultured with the SKOV3 ovarian cancer cell line for another 24 h. Macrophages were collected for real-time PCR and Western blot to detect the expression of B7-H1, and activation of the NF-${\kappa}B$ signaling pathway. Moreover, supernatants were collected to assay for IL-12, IFN-${\gamma}$ and IL-10 by ELISA. In addition, monocyte-derived macrophages treated with IFN-${\gamma}$ were cocultured with SKOV3 and determined for the expression of B7-H1. Furthermore, the expression of B7-H1 in monocyte-derived macrophages was also evaluated after blocking NF-${\kappa}B$ signaling. Results: The expression of B7-H1 was significantly upregulated in monocyte-derived macrophages treated with rIL-12 or Ad-IL-12-GFP compared with the control groups (p<0.05), accompanied by a remarkable upregulation of IFN-${\gamma}$ (p<0.05), a marked downregulation of IL-10 (p<0.05) and activation of NF-${\kappa}B$ signaling. However, the upregulation of B7-H1 was inhibited by blocking the NF-${\kappa}B$ signaling pathway (p<0.05). Expression of B7-H1 was also increased (p<0.05) in monocyte-derived macrophages treated with IFN-${\gamma}$ and cocultured with SKOV3. By contrast, the expression of B7-H1 in THP-1-derived macrophages was significantly decreased when treated in the same way as monocyte-derived macrophages (p<0.05), and IL-10 was also significantly decreased but IFN-${\gamma}$ was almost absent. Conclusions: IL-12 upregulates the expression of B7-H1 in monocyte-derived macrophages, which is possible though inducing the secretion of IFN-${\gamma}$ and further activating the NF-${\kappa}B$ signal pathway. However, IL-12 downregulates the expression of B7-H1 in THP-1-derived macrophages, associated with a lack of IFN-${\gamma}$ and inhibition of expression of IL-10. -
Wen, Ying;Pan, Xiong-Fei;Zhao, Zhi-Mei;Chen, Feng;Fu, Chun-Jing;Li, Si-Qi;Zhao, Yun;Chang, Hong;Xue, Qing-Ping;Yang, Chun-Xia 5773
Background: Since cervical cancer can be prevented and controlled through human papillomavirus (HPV) vaccination, it is important to train health care providers and provide them with appropriate knowledge. This study aimed to understand the level of HPV related knowledge among medical students and correlates in Southwest China in order to address any potential gap in their knowledge base. Methods: We conducted a cross-sectional survey among medical students in six selected universities across Southwest China based on a pretested questionnaire regarding HPV infection, cervical cancer, and HPV vaccines. Results: We successfully surveyed 1, 878 medical students, of whom 32.1% were males and 67.9% were females. Their mean age was 20.8 (standard deviation: 1.3) years. 91.8% of them were ethnic Han Chinese, and 43.8% were students in clinical medicine. While 76.5% had heard of HPV only 48.8% knew that the prevention of cervical cancer was possible through HPV vaccination. Only 42.9% of the male and 49.2% of the female students correctly answered over 10 out of 22 questions on HPV related knowledge. Female students appeared to know more about HPV and HPV vaccination (OR: 1.39; 95% CI: 1.11-1.75). In addition, the student knowledge improved with the grade (p<0.001). University courses were the most selected source of knowledge about HPV vaccination (66.4%). 83.6% of males and 91.4% of females were willing to have more HPV related education by experts (p<0.001). Only 10.1% of the students acknowledged that people had asked for their advice regarding HPV vaccination. Conclusions: Our survey indicates that medical students from Southwest China have poor knowledge of HPV and HPV vaccination, but are willing to receive more relevant information. Targeted education should be incorporated into school courses to inform these future health care providers and ensure success of programs for cervical cancer control and prevention. -
Tobing, Maringan Diapari Lumban;Sahiratmadja, Edhyana;Dinda, Mufti;Hernowo, Bethy Suryawathy;Susanto, Herman 5781
Background: As in other developing countries, cervical cancer is the most frequent gynecologic malignancy in Indonesia. Persistent high risk genotypes of human papillomavirus (HPV) that infect the cervical tissue have been established as the etiology of cervical cancer. This study aimed to explore the profile of cervical cancer patients and the infected HPV genotypes at Dr. Hasan Sadikin General Hospital-Bandung. Materials and Methods: During the year 2010, 554 cervical cancer patients were registered. In a subset of the patients during July - November 2010, 40 randomized fresh biopsies were tested for HPV genotype after obtained informed consent. The distribution of HPV genotypes and the association to risk factors were analysed. Results: The result showed that 62.5% of the tested biopsies were infected by multiple HPV infections, with HPV-16 found in most of the cervical cancer patients (90%). Marriage at age younger than 16 years old was statistically significant in relation to multiple HPV infection (p=0.003), but not parity more than three times (p=0.59). Conclusions: Although high paritiy in our study was not associated with multiple HPV infection, good family planning programs and reproductive health education need to be emphasized in Indonesia as high parity and marriage at young age might increase the chance of cervical cancer development. -
Park, Sun-A;Cho, Sung Sook;Kwak, Gyu Jin 5787
Background: With increasing survival periods and diversification of treatment methods, treatment of critically ill cancer patients has become an important factor influencing patient prognosis. Patients with cancer are at high risk of infections and subsequent complications. This study investigated the incidence and factors contributing to the development of ventilator-associated pneumonia (VAP). Materials and Methods: This retrospective study investigated the incidence of VAP and factors leading to infection in patients admitted to the intensive care unit (ICU) of a cancer center from January 1, 2012 to December 31, 2013. Results: The incidence of VAP was 2.13 cases per 1,000 days of intubation, and 13 of 288 patients (4.5%) developed VAP. Lung cancer was the most common cancer associated with VAP (N=7, 53.9%), and longer hospital stays and intubation were associated with increased VAP incidence. In the group using a "ventilator bundle," the incidence was 1.14 cases per 1,000 days compared to 2.89 cases per 1,000 days without its use; however, this difference was not statistically significant (p=0.158). Age (${\geq}65$ , OR=5.56, 95% confidence interval [CI]=1.29-23.95), surgery (OR=3.78, 95%CI=1.05-13.78), and tracheotomy (OR=4.46, 95%CI=1.00-19.85) were significant VAP risk factors. The most common causative organisms were methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (N=4, 30.8% each), followed by Acinetobacter baumannii and Candida albicans (N=2, 15.4% each). Conclusions: The incidence of pneumonia among critically ill cancer patients is highest in those with lung cancer, but lower than among non-cancer patients. The length of hospital stay and time on mechanical ventilation are important risk factors for development of VAP. Although not statistically significant, "ventilator bundle" care is an effective intervention that delays or reduces incidence of VAP. Major risk factors for VAP include age (${\geq}65$ years), surgery, and tracheostomy, while fungi, gram-negative bacteria, and multidrug-resistant organisms were identified as the major causative pathogens of VAP in this study. -
Lu, Ming;Tian, Yu;Yue, Wei-Ming;Li, Lin;Li, Shu-Hai;Qi, Lei;Hu, Wen-Si;Gao, Cun;Si, Li-Bo;Tian, Hui 5793
Background: Golgi phosphoprotein-3 (GOLPH3) is implicated in cancer development and progression. The aim of this study was to evaluate the prognostic significance of GOLPH3 protein and its association with tumor angiogenesis in patients with early-stage NSCLC. Materials and Methods: Immunohistochemistry was performed to determine GOLPH3 protein expression and allow assessment of intratumoral microvessel density (MVD) by counting CD-34 positive immunostained endothelial cells. Correlations of expression with MVD, clinicopathologic features and clinical prognosis were analyzed. Results: A notably higher level of GOLPH3 expression was found in early-stage NSCC tissues at the protein level. However, we do not find any correlation between GOLPH3 expression and clinicopathologic features (p>0.05), although higher MVD was positively associated with GOLPH3 overexpression (p<0.001). Expression of GOLPH3 was found to be an independent prognostic factor in early-stage NSCLC patients, those expressing high levels of GOLPH3 exhibiting a substantially lower 5-year overall survival than GOLPH3-negative patients (adjusted HR =1.899, 95% CI: 1.021-3.532, p=0.043). Conclusions: High expression of the GOLPH3 protein is common in early-stage NSCC, and is closely associated with tumor progression, increased tumor angiogenesis, and poor survival. We conclude a possibility of its use as a diagnostic and prognostic marker in early-stage NSCC patients. -
Sun, Yi-Xin;Cheng, Wen;Han, Xue;Liu, Zhao;Wang, Qiu-Cheng;Shao, Hua 5799
Background: Radiofrequency ablation (RFA) is the most widely used and studied method internationally for the local treatment of liver tumors. However, the extension of coagulation necrosis in one RFA procedure is limited and incomplete coverage of the damaged area can lead to a high local recurrence rate. Objective: In this study, we compared the effects of different solutions in enhancing hepatic radiofrequency by establishing a rabbit VX2 liver cancer model. We also determined the optimal solution to maximise effects on the extent of RFA-induced coagulation necrosis. Methods: Thirty VX2 tumor rabbits were randomly assigned to five groups: group A, RFA alone; group B, RFA with anhydrous ethanol injection; group C, RFA with 5% hypertonic saline injection; group D, RFA with lidocaine injection; and group E, RFA with a mixed solution. Routine ultrasound examinations and contrast-enhanced ultrasound (CEUS) of the ablation areas were performed after RFA. Then, we measured the major axis and transverse diameter and compared the areas of coagulation necrosis induced by RFA. Results: The mean ablation area range increased in groups B, C and especially E, and the scopes were greater compared with group A. Preoperative application of anhydrous ethanol, hypertonic saline, lidocaine and the mixed solution (groups B, C, D and E, respectively) resulted in larger coagulation necrosis areas than in group A (p<0.05). Among the groups, the coagulation necrosis areas in group E was largest, and the difference was statistically significant compared with other groups (p<0.05). Pathological findings were consistent with imaging results. Conclusions: A mixture of dehydrated alcohol, hypertonic saline and lidocaine injected with RFA increases the extent of coagulation necrosis in the liver with a single application, and the mixed solution is more effective than any other injection alone. -
Ronco, Alvaro Luis;Mendilaharsu, Maria;Boffetta, Paolo;Deneo-Pellegrini, Hugo;Stefani, Eduardo De 5805
In the time period 1996-2004, all incident cases of bladder cancer were included in a case-control study in order to study the role of meat consumption and product animals in the etiology of urothelial cancer. The study included 225 cases and 1,510 hospitalized controls with non-neoplastic conditions, not related to smoking and alcohol drinking. Relative risks, approximated by the odds ratios, were calculated in order to clarify the effect of meat consumption in the etiology of urothelial cancer. Total meat consumption (OR 1.47, 95% CI 1.02-2.11), total processed meat (OR 1.57, 95% CI 1.08-2.27), frankfurters (hot dogs) (OR 2.03, 95% CI 1.28-3.21), ham (OR 1.79, 95% CI 1.21-2.67) and salted meat (OR 2.73, 95% CI 1.78-4.18) were positively associated with risk of bladder cancer. Animal products, like cheese, whole milk, and total eggs were also associated with bladder cancer risk (OR for eggs 4.05, 95% CI 2.68-6.12). In conclusion, total meat, processed meat, and eggs could play an important role in the etiology of bladder cancer in Uruguay. -
Chundarat, Pong-Anan;Suwannarurk, Komsun;Bhamarapravatana, Kornkarn;Pattaraarchachai, Junya;Thaweekul, Yuthadej;Mairaing, Karicha;Poomtavorn, Yenrudee 5811
Background: To investigate abnormal cervical histopathology (ACH) from hysterectomy specimens with normal preoperative Papanicolaou (Pap) smears. Materials and Methods: Medical records from May 2009 to April 2012 were retrospectively reviewed of subjects from whom hysterectomy specimens were taken in Thammasat University Hospital. All had normal preoperative Pap smears. ACH was the primary outcome. A p-value less than 0.05 was considered significant. A total of 483 subjects with an average age of 50.5 years were recruited. Benign cases of enlarged uterus and pelvic mass were present in 94% (430/483). Endometrial and ovarian cancer were found at 6.2 and 4.7%, respectively. In hysterectomy specimens there were 19 (4%) cases of ACH. Silent ACH with benign disease, endometrial and ovarian cancers were 1.2% (5/430), 33.3% (10/30) and 17.4% (4/23), respectively. The negative predictive value (NPV) and false negative rate of Pap smears were 96 and 4%, respectively. ACH in malignant cases were 27.9% (12/43) and 20% (2/10) in adequate (APS) and inadequate (IPS) Pap collection groups, respectively. ACH in benign condition were 0.68% (2/292) and 2.2% (3/138) in APS and IPS, respectively. ACH was more often found in hysterectomy specimens with indication of malignancy than benign conditions with statistical significance. One third of preoperative stage I endometrial cancer cases had cervical involvement. Conclusions: Silent ACH in normal preoperative Pap smear was 4 %. Inadequate Pap smear collection is still the major problem in this study. Reducing inadequate Pap smear collection could reduce the false negative rate. -
Zhao, Lian-Mei;Zheng, Zhao-Xu;Zhao, Xiwa;Shi, Juan;Bi, Jian-Jun;Pei, Wei;Feng, Qiang 5815
For an exact comparison of mRNA transcription in different samples or tissues with real time quantitative reverse transcription-polymerase chain reaction (qRT-PCR), it is crucial to select a suitable internal reference gene. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and beta-actin (ACTB) have been frequently considered as house-keeping genes to normalize for changes in specific gene expression. However, it has been reported that these genes are unsuitable references in some cases, because their transcription is significantly variable under particular experimental conditions and among tissues. The present study was aimed to investigate which reference genes are most suitable for the study of gastric cancer tissues using qRT-PCR. 50 pairs of gastric cancer and corresponding peritumoral tissues were obtained from patients with gastric cancer. Absolute qRT-PCR was employed to detect the expression of GAPDH, ACTB, RPII and 18sRNA in the gastric cancer samples. Comparing gastric cancer with corresponding peritumoral tissues, GAPDH, ACTB and RPII were obviously upregulated 6.49, 5.0 and 3.68 fold, respectively. Yet 18sRNA had no obvious expression change in gastric cancer tissues and the corresponding peritumoral tissues. The expression of GAPDH,${\beta}$ -actin, RPII and 18sRNA showed no obvious changes in normal gastric epithelial cells compared with gastric cancer cell lines. The carcinoembryonic antigen (CEA), a widely used clinical tumor marker, was used as a validation gene. Only when 18sRNA was used as the normalizing gene was CEA obviously elevated in gastric cancer tissues compared with peritumoral tissues. Our data show that 18sRNA is stably expressed in gastric cancer samples and corresponding peritumoral tissues. These observations confirm that there is no universal reference gene and underline the importance of specific optimization of potential reference genes for any experimental condition. -
Chu, Xiao;Zhu, Cheng-Chu;Liu, Hui;Wang, Jiao-Chen 5819
Purpose: To investigate the expression of hypoxia-inducible factor prolyl hydroxylase 3 (HIFPH3) in non-small cell lung cancer (NSCLC) and explore the correlation of HIFPH3 expression with lymph node metastasis and microvessel density (MVD). Materials and Methods: A total of 73 cases of NSCLC specimens, 24 cases of para-cancerous tissues, and 20 normal pulmonary tissues were collected for HIFPH3 and CD31 immunohistochmical (IHC) study. Microvessel density (MVD) of the NSCLC tissues was also determined based on the expression of CD31. Results: The expression of HIFPH3 in carcinoma tissue was statistically higher than para-cancerous and normal pulmonary tissues (${\chi}^2=48.806$ , p<0.05). Compared withthe negative lymph node metastasis group, the lymph node metastasis group showed significantly higher HIFPH3 expression (${\chi}^2=6.300$ , p<0.05). The strong HIFPH3+group displayed a significantly higher MVD than weak HIFPH3+ and HIFPH3- groups (p<0.05). No differences in positive HIFPH3 expression were noted regarding the tumor diameter, age, smoking status, gender of NSCLC patients, tumor size, histopathology, or differentiation. Conclusions: HIFPH3 expression in human NSCLC lesions is significantly higher than that in para-cancerous and normal lung tissues and is positively associated with lymph node metastasis and MVD. -
Sader-Ghorra, Claude;Rassy, Marc;Naderi, Samah;Kourie, Hampig Raphael;Kattan, Joseph 5825
Background: Lymphomas represent the fifth most frequent cancer in Lebanon. However, little is known concerning epidemiologic characteristics and distribution of lymphoid neoplasms according to the 2008 WHO classification. Materials and Methods: We conducted a retrospective study of lymphoma cases diagnosed from 2008 till 2012 at$H\hat{o}tel$ -Dieu de France University Hospital. Results: A total of 502 new cases of lymphoma were diagnosed at our institution during a five year period: 119 cases (24%) were Hodgkin lymphomas (HL) and 383 cases (76%) were non-Hodgkin lymphomas (NHL). HLs were equally distributed in both sexes with a mean age at diagnosis of 30 years. Among NHL, 87% (332 cases) were B cell lymphomas, 9% (34 cases) were T cell lymphomas and 4%(17 cases) were classified as precursor lymphoid neoplasms. Among B cell lymphomas, 44% (147 cases) were diffuse large B cell lymphomas (DLBCL), 20% (65 cases) follicular lymphomas and 8% (27 cases) mantle cell lymphomas. DLBCL were equally distributed in both sexes with a mean age of 58 years. Follicular lymphomas were characterized by a male predominance (57%) and a mean age of 60 years. Mantle cell lymphomas showed a pronounced male predominance (85%) with a mean age of 60 years in men and 70 years in women. Some 72% of patients having T cell lymphomas were men, with a mean age of 57 years in men and 45 years in women, while 65% of patients having precursor lymphoid neoplasms were women with a mean age of 22 years in women and 30 years in men. Conclusions: The lymphoma subtype distribution in Lebanon is unique when compared to other countries from around the world. In fact, Hodgkin and follicular lymphomas are more frequent than in most Far Eastern, European and American countries, while T-cell lymphomas and DLBCL are less frequent. -
Stefani, Eduardo De;Boffetta, Paolo;Ronco, Alvaro Luis;Deneo-Pellegrini, Hugo;Correa, Pelayo;Acosta, Gisele;Mendilaharsu, Maria 5829
Background: The role of processed meat in the aetiology of squamous cell oesophageal cancer has been explored in detail. Methods: In the time period 1990-2005, a case-control study was conducted in Montevideo, Uruguay including 2,368 participants (876 cases of oesophageal cancer and 1,492 controls). Relative risks, approximated by the odds ratios, were estimated by multiple unconditional logistic regression. Results: Processed meat was positively associated with oesophageal cancer (upper quartile vs lower quartile OR 2.30, 95%CI 1.72-3.07), whereas salted meat intake was positively associated with squamous cell oesophageal cancer (OR 3.82, 95%CI 2.74-5.33). Finally other cured meats were positively associated with oesophageal cancer (OR 1.65, 95%CI 1.22-2.22). Conclusions: It could be concluded that processed meat consumption could be an important risk factor for the aetiology of squamous cell oesophageal cancer in Uruguay. -
Lin, Wen-Li;Sun, Jia-Ling;Chang, Shu-Chan;Wu, Pei-Hua;Huang, Wen-Tsung;Tsao, Chao-Jung 5835
Background: Gastric cancer is one of the most common causes of cancer death in Taiwan. The literature has previously shown that age, tumor site, T categories, and number of metastatic nodes significantly affect prognosis. The aim of this study was to determine the long-term survival of patients with gastric cancer, as well as the effect of particular prognostic factors on survival. Materials and Methods: This was a survival analysis study with retrospective design. We reviewed the records of 64 patients with adenocarcinoma of the stomach who had undergone gastrectomy with curative intent between 2009 and 2012 at a teaching hospital in southern Taiwan. Data extracted from patient documents included age, gender distribution, tumor location, and pathological grading. Results: The median follow-up time was 4 years, and there were 31 deaths attributed to gastric cancer. Kaplan-Meier analysis revealed that retrieval of less than 15 lymph nodes from a patient was a significant predictor of survival. A significant predictor of poorer survival was higher pathological grading. Conclusions: Our results indicate that the number of lymph nodes retrieved and pathological grading could be viewed as crucial prognostic factors affecting the survival of individuals with gastric cancer. -
Du, Ling-Bin;Li, Hui-Zhang;Wang, Xiang-Hui;Zhu, Chen;Liu, Qing-Min;Li, Qi-Long;Li, Xue-Qin;Shen, Yong-Zhou;Zhang, Xin-Pei;Ying, Jiang-Wei;Yu, Chuan-Ding;Mao, Wei-Min 5839
Objective: The Zhejiang Provincial Cancer Prevention and Control Office collected cancer registration data during 2000 to 2009 from 6 cancer registries in Zhejiang province of China in order to analyze the cancer incidence. Methods: Descriptive analysis included cancer incidence stratified by sex, age and cancer site group. The proportions and cumulative rates of 10 common cancers in different groups were also calculated. Chinese population census in 1982 and Segi's population were used for calculating age-standardized incidence rates. The log-linear model was used for fitting to calculate the incidence trends. Results: The 6 cancer registries in Zhejiang province in China covered a total of 60,087,888 person-years during 2000 to 2009 (males 30,445,904, females 29,641,984). The total number of new cancer cases were 163,104 (males 92,982, females 70,122). The morphology verified cases accounted for 69.7%, and the new cases verified only by information from death certification accounted for 1.23%. The crude incidence rate in Zhejiang cancer registration areas was$271.5/10^5$ during 2000 to 2009 (male$305.41/10^5$ , female$236.58/10^5$ ), age-standardized incidence rates by Chinese standard population (ASIRC) and by world standard population (ASIRW) were$147.1/10^5$ and$188.2/10^5$ , the cumulative incidence rate (aged from 0 to 74) being 21.7%. The crude incidence rate was$209.6/10^5$ in 2000, and it increased to$320.20/10^5$ in 2009 (52.8%), with an annual percent change (APC) of 4.51% (95% confidence interval, 3.25%-5.79%). Age-specific incidence rate of 80-84 age group was achieved at the highest point of the incidence curve. Overall with different age groups, the cancer incidences differed, the incidence of liver cancer being highest in 15-44 age group in males; the incidence of breast cancer was the highest in 15-64 age group in females; the incidences of lung cancer were the highest in both males and females over the age of 65 years. Conclusions: Lung cancer, digestive system malignancies and breast cancer are the most common cancers in Zhejiang province in China requiring an especial focus. The incidences of thyroid cancer, prostate cancer, cervical cancer and lymphoma have increased rapidly. Prevention and control measures should be implemented for these cancers. -
Moderating Effects of Media Exposure on Associations between Socioeconomic Position and Cancer WorryJung, Minsoo;Chan, Carina Ka Yee;Viswanath, Kasisomayajula 5845
Reducing fear of cancer is significant in developing cancer screening interventions, but the levels of fear may vary depending on the degrees of media exposure as well as individuals' socioeconomic positions (SEP). However, few studies have examined how the SEP influences the fear of cancer under the moderating process of general and specific forms of media exposure. We investigated the moderating effect of media exposure on the relationship between SEP and the level of fear of cancer by assuming that cancer knowledge is a covariate between those two. In particular, this study examined how exposure to both general and specific media changes the series of processes from SEP to fear of cancer. We conducted path analyses with three types of media - television, radio and the Internet- using data from a health communication survey of 613 adults in Massachusetts in the United States. We found that SEP influences cancer knowledge directly and fear of cancer indirectly, as moderated by the level of media exposure. Health-specific exposure, however, had a more consistent effect than general media exposure in lowering the fear of cancer by increasing knowledge about cancer. A higher level of health-specific exposure and greater amount of cancer knowledge lessened the fear of cancer. In addition, the more people were exposed to health information on television and the Internet, the lower the level of fear of cancer as a result. These findings indicate a relationship between SEP and fear of cancer, as moderated by the level and type of media exposure. Furthermore, the findings suggest that for early detection or cancer prevention strategies, health communication approaches through mass media need to be considered. -
Background: Methylenetetrahydrofolate (MTHFR) is the key enzyme of the folate metabolic pathway and several studies have pointed to association between the MTHFR C677T polymorphism and breast cancer risk. Although significant association was observed in some studies, in others no clear link could be established. Objective: A meta-analysis of published Asian case control studies was therefor carried out to shed further light on any C677T breast cancer association. Materials and Methods: PubMed, Springer Link, Google Scholar and Elsevier databases were searched for case control studies of associations between MTHFR C677T polymorphism and breast cancer risk. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. A total of 36 studies including 8,040 cases and 10,008 controls were included in the present meta-analysis. Results: Overall, a significantly elevated breast cancer risk was associated with the T allele and TT genotype in homozygote comparison and dominant genetic models when all studies were pooled into the meta-analysis (T vs C (allele contrast model): OR=1,23, 95%CI=1.13-1.37, p=0.000 ; TT vs CC(homozygote model): OR=1.38, 95%CI=1.16-1.63, p=0.0003; TT+CT vs CC (dominant model): OR=1.12, 95%CI=1.01-1.23, p=0.02). Conclusions: The present meta-analysis strongly suggested a significant association between the MTHFR C677T polymorphism and risk of breast cancer in Asian populations.
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Gan, Li-Li;Zhang, Hao;Guo, Ji-Hua;Fan, Ming-Wen 5861
High risk forms of the human papilloma virus (HPV) are generally accepted as necessary causative agents for cervical cancer. Recently, a possible relation between HPV and oral squamous cell carcinoma (OSCC) has also been noticed. The present study was conducted to investigate the prevalence of HPV infection in OSCCs in Wuhan city. DNA samples were collected from fresh tissues in 200 patients with OSCC and 68 normal controls. The polymerase chain reaction and direct sequencing were used to identify the HPV types in the samples. The prevalence of HPV of all types in the OSCC group was higher than in the control group (55/200 vs 2/68, OR=11.5, 95% CI=2.6-50.2). HPV16 and HPV18 were the main types detected, with HPV6 was the only low-risk type identified. High-risk HPV types HPV16 and HPV18 are prevalent in OSCC patients and may participate in the development of OSCC with traditional risk factors, tobacco and alcohol, possibly exerting synergistic effects. The results of multinomial logistic regression showed that those who smoked, consumed alcohol and with HPV infection have the highest risk of developing oral cancer (OR=13.3, 95% CI=3.1-56.8). Adjusted for age, smoking and alcohol use, HPV infection was independently associated with oral squamous cell carcinoma. -
Hao, Yi;Yuan, Jian-Ling;Abudula, Abulizi;Hasimu, Axiangu;Kadeer, Nafeisha;Guo, Xia 5867
Background: Cervical cancer is listed as one of high-incidence endemic diseases in Xinjiang. Our study aimed to evaluate the expression of TLR9 in uterine cervical tissues of Uyghur women and examine associations with clinicopathological variables. We further characterized the direct effects of TLR9 upon the selective silencing of human papillomavirus (HPV) E6 and E7 oncoprotein expression in HPV 16-positive human cervical carcinoma cells treated with siRNA in vitro. Materials and Methods: Immunohistochemistry was applied to evaluate TLR9 expression in 97 formalin-fixed paraffin-embedded cervical samples from Uyghur women; 32 diagnosed with cervical squamous cell carcinomas (CSCC), 14 with low-grade cervical intraepithelial neoplasias (CINI), 10 medium-grade (CINII), 24 high-grade (CINIII), and 17 chronic cervicitis.$BLOCK-iT^{TM}$ U6 RNAi Entry Vector$pENTR^{TM}$ /U6-E6 and E7 was constructed and transfected the entry clone directly into the mammalian cell line 293FT. Then the HPV 16-positive SiHa human cervical carcinoma cell line was infected with RNAi recombinant lentivirus. RT-PCR and Western blotting were used to determine the expression of TLR9 in both SiHa and HPV 16 E6 and E7 silenced SiHa cells. Results: Immunohistochemical staining showed that TLR9 expression was undetectable (88.2%) or weak (11.8%) in chronic cervicitis tissues. However, variable staining was observed in the basal layer of all normal endocervical glands. TLR9 expression, which was mainly observed as cytoplasmic staining, gradually increased in accordance with the histopathological grade in the following order: chronic cervicitis (2/17, 11.8%)Thongchot, Suyanee;Yongvanit, Puangrat;Loilome, Watcharin;Seubwai, Wanchana;Phunicom, Kutcharin;Tassaneeyakul, Wichittra;Pairojkul, Chawalit;Promkotra, Wisuttiphong;Techasen, Anchalee;Namwat, Nisana 5873
Hypoxia and autophagy are known to facilitate tumor progression. We here aimed to investigate the role of hypoxia-associated autophagy in cholangiocarcinoma (CCA) survival and metastasis. Immunostaining of hypoxic-responsive proteins (HIF-$1{\alpha}$ and BNIP3) and a key regulator of autophagy (PI3KC3) were examined in CCA tissues and their expression levels were compared with clinicopathological parameters. A hypoxia mimicking condition ($CoCl_2$ treatment) was also tested regarding CCA cell functions. Our results showed that HIF-$1{\alpha}$ (66%), BNIP3 (44%) and PI3KC3 (46%) showed strong staining in human CCA tissues. Positive expression of HIF-$1{\alpha}$ (p=0.033), BNIP3 (p=0.040) and PI3KC3 (p=0.037) was significantly correlated with lymph node metastasis. HIF-$1{\alpha}$ was well associated with BNIP3 (r=0.3, p<0.01) and PI3KC3 (r=0.2, p<0.01). The survival rates of patients who were positive with HIF-$1{\alpha}$ (p=0.047) or co-expressed HIF-$1{\alpha}$ and BNIP3 (p=0.032) or HIF-$1{\alpha}$ and PI3KC3 (p=0.043) were significantly greater than in the negative groups. CCA cells treated with$CoCl_2$ showed an increase in HIF-$1{\alpha}$ , BNIP3, PI3KC3 and LC3-II, with increased cell migration and pFAK levels. These data suggest that hypoxia associated autophagy enhances CCA metastasis, resulting in a poor prognosis of CCA.Laowahutanont, Piyawat;Karalak, Anant;Wongsena, Metee;Loonprom, Komson;Pukcharoen, Phuttalak;Jamsri, Paphawin;Sangrajrang, Suleeporn 5879
High-risk (HR) human papillomavirus (HPV) testing is important in cervical cancer screening for triage colposcopy. The objective of the study was to evaluate the prevalence of HR HPV infection with different cervical cytological features among women undergoing health examination. A total of 2,897 women were retrospectively evaluated between May 2011 to December 2011. DNA was extracted from residual specimens collected during routine liquid-based cytology tests at the National Cancer Institute. Overall, HR HPV prevalence was 9.3% including 1.6% of HPV-16 and 0.4% of HPV-18. Of all 270 HPV positive samples, 211 (78.1% were HR-HPV non 16/18; 47 (17.4%) were HPV-16 and 12 (4.4%) were HPV-18. The prevalence of HPV infection was similar in all age groups, although a higher rate was observed in women age 31-40 years. Among women with normal cytology, HR HPV positive were found in 6.7%. In abnormal cytology, HR HPV were found 46.7% in atypical squamous cells (ASC), 54.8% in low-grade squamous intraepithelial lesions (LSIL) and 80.0% in high-grade squamous intraepithelial lesions (HSIL). HPV-16 was detected in 8.6%, 6.4% and 12.0% of ASC, LSIL and HSIL, respectively. The results of this study provide baseline information on the HPV type distribution, which may be useful for clinicians to decide who should be monitored or treated more aggressively.Faradmal, Javad;Soltanian, Ali Reza;Roshanaei, Ghodratollah;Khodabakhshi, Reza;Kasaeian, Amir 5883
Background: Breast cancer is the most common cancers in female populations. The exact cause is not known, but is most likely to be a combination of genetic and environmental factors. Log-logistic model (LLM) is applied as a statistical method for predicting survival and it influencing factors. In recent decades, artificial neural network (ANN) models have been increasingly applied to predict survival data. The present research was conducted to compare log-logistic regression and artificial neural network models in prediction of breast cancer (BC) survival. Materials and Methods: A historical cohort study was established with 104 patients suffering from BC from 1997 to 2005. To compare the ANN and LLM in our setting, we used the estimated areas under the receiver-operating characteristic (ROC) curve (AUC) and integrated AUC (iAUC). The data were analyzed using R statistical software. Results: The AUC for the first, second and third years after diagnosis are 0.918, 0.780 and 0.800 in ANN, and 0.834, 0.733 and 0.616 in LLM, respectively. The mean AUC for ANN was statistically higher than that of the LLM (0.845 vs. 0.744). Hence, this study showed a significant difference between the performance in terms of prediction by ANN and LLM. Conclusions: This study demonstrated that the ability of prediction with ANN was higher than with the LLM model. Thus, the use of ANN method for prediction of survival in field of breast cancer is suggested.Wang, Jun;Yu, Jin-Ming;Jing, Shao-Wu;Guo, Yin;Wu, Ya-Jing;Li, Na;Jiao, Wen-Peng;Wang, Li;Zhang, Yan-Jun 5889
Over-expression of epidermal growth factor receptor (EGFR) has been identified as a common feature associated with clinical outcome in many types of cancer, including squamous cell carcinoma of the oesophagus (SCCO). However, the clinical importance of EGFR over-expression in SCCO remains unsettled as conflicting results exist. Therefore we carried out the present meta-analysis of published studies for clarification. A total of 13 studies including 1, 150 patients were enrolled. EGFR over-expression was positive in 722 of these cases. With EGFR over-expression, patients had higher depth of invasion, vascular invasion, and poor prognosis. However, expression had no relation with degree of differentiation, histological grade, lymph node metastasis, clinical stage or lymphatic invasion. EGFR over-expression is probably a valuable predictor for the T stage, vascular invasion and OS, and it could be used as a poor prognosis indicator for the esophageal SCC patients. Targeting therapy to EFGR should be considered to the combined treatment in SCCO.Bu, De-Yun;Ji, Wen-Wu;Bai, Dan;Zhou, Jian;Li, Hai-Xia;Yang, Hui-Fang 5895
Background: Metabolic syndrome (MS) is a cluster of complicated disorders caused by the interactive influencing factors of heredity and environment, which predisposes to many cnacers. Results from epidemic research indicate that stress is tightly related to the pathogenesis of MS and neoplasia. This paper aims to investigate the association between psychological stress and MS with respect to the tumor necrosis factor alpha (TNF${\alpha}$ ) and neuropeptide Y (NPY) genes in the Han and Hui ethnic groups. Methods: All subjects for this case-control study matched strict enrollment criteria (nationality, gender and age) and lived in the city of Wu Zhong of Ningxia Province in China. The enrolled group contained 102 matched pairs of Hui ethnic individuals and 98 matched pairs of Han ethnic individuals. Enrolled subjects completed the general Symptom Checklist-90 (SCL-90). The TNF${\alpha}$ -308G/A variant and NPYrs16147 polymorphism were detected in case (81 males, 119 females) and control (81 males, 119 females) groups by polymerase chain reaction (PCR) amplification. Results: Nine factors of the SCL-90 were found to be statistically different (p<0.05) between case and control groups. The homozygous mutant genotype (AA) and the mutant allele (A) of the TNF${\alpha}$ -308G/A gene were less frequently observed in the control population compared to the case group. The odds ratio (95% confidence interval) in "Allele" for MS was 2.28 (1.47-3.53), p=0.0001, while "OR" was 1.11 (0.83-1.47), p=0.15, for the NPYrs16147 gene polymorphism. Conclusions: Psychological stress has been positively associated with MS. A previous study from our group suggested there were differences in the level of psychological stress between Hui and Han ethnic groups. Furthermore, we found that the stress-related TNF${\alpha}$ gene was associated with MS for both Han and Hui ethnic groups. In contrast, NPY may be a possible contributor to MS and associated cancer for the Han ethnic group.Roder, David Murray;Ward, Gail Heather;Farshid, Gelareh;Gill, Peter Grantley 5901
Background: Data from BreastScreen Australia Screening and Assessment Services (SAS) for 2002-2010 were analysed to determine whether some SAS characteristics were more conducive that others to high screening performance, as indicated by high priority performance indicators and standards. Materials And Methods: Indicators investigated related to: numbers of benign open biopsies, screen-detected invasive cancers, and interval cancers, and wait times between screening and assessment. Multivariate Poisson regression was undertaken using as candidate predictors of performance, SAS size (screening volume), urban or rural location, year of screening, accreditation status, and percentages of clients from culturally and linguistically diverse backgrounds, rural and remote areas, and socio-economically disadvantaged areas. Results: Performance standards for benign biopsies and invasive cancer detection were uniformly met irrespective of SAS location and size. The interval cancer standard was also met, except in 2003 when the 95% confidence interval of the rate still incorporated the national standard. Performance indicators improved over time for: benign open biopsy for second or subsequent screening rounds; rates of invasive breast cancer detection for second or subsequent screening rounds; and rates of small cancer detection. No differences were found over time in interval cancer rates. Interval cancer rates did not differ between non-metropolitan and metropolitan SAS, although state-wide SAS had lower rates. The standard for wait time between screening and assessment (being assessed${\leq}28$ days) was mostly unmet and this applied in particular to SAS with high percentages of culturally and linguistically diverse women in their screening populations. Conclusions: Gains in performance were observed, and all performance standards were met irrespective of SAS characteristics, except wait times to assessment. Additional descriptive data should be collected on SAS characteristics, and their associations with favourable screening performance, as these may be important when deciding on SAS designRamanathan, Priya;Ganeshrajah, Selvaluxmy;Raghanvan, Rajalekshmi Kamalalayam;Singh, Shirley Sundar;Thangarajan, Rajkumar 5909
Human papillomavirus infection (HPV) and HPV related immune perturbation play important roles in the development of cervical cancer. Since mature dendritic cells (DCs) are potent antigen-presenting cells (APC), they could be primed by HPV antigens against cervical cancers. In this study we were able to generate, maintain and characterize, both phenotypically and functionally, patient specific dendritic cells in vitro. A randomized Phase I trial with three arms - saline control (arm I), unprimed mature DC (arm II) and autologous tumor lysate primed mature DC (arm III) and fourteen patients was conducted. According to WHO criteria, grade 0 or grade one toxicity was observed in three patients. One patient who received tumor lysate primed dendritic cells and later cis-platin chemotherapy showed a complete clinical response of her large metastatic disease and remained disease free for more than 72 months. Our findings indicate that DC vaccines hold promise as adjuvant sfor cervical cancer treatment and further studies to improve their efficacy need to be conducted.Feng, Lei;Li, Jie;Yan, Ling-Di;Tang, Jian 5917
Background: This study aimed to explore the effects of ras association domain family 1 A (RASSF1A) on proliferation and apoptosis of human cervical cancer cell line Hela cells. Materials and Methods: RASSF1A was cloned into the pcDNA3.1(+) vector to generate pcDNA3.1(+)-RASSF1A plasmid for transfection into Hela cells. Changes in the proliferation and apoptosis of cultured Hela cells were examined by the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium chloride assay and flow cytometry. A protein array was used to analyze the expression of apoptotic factors. Results: Plasmid pcDNA3.1(+)-RASSF1A was generated and transfected into Hela cells to stably express RASSF1A in Hela cells. RASSF1A transfection was effective in inhibiting the proliferation of Hela cells up to 52.4%, as compared to cells transfected with an empty plasmid. RASSF1A expression also successfully induced apoptosis in human cervical cells with an apoptosis rate of 20.5%. More importantly, protein array results showed that RASSF1 A transfection induced overexpression of p21 and caspase 8, while decreasing the expression of survivin in Hela cells. Conclusions: RASSF1A expression was effective in suppressing the proliferation and increasing apoptosis of Hela cells, and may be a potential therapy for cervical cancer in clinic.Liu, Xiao-Yun;Zhu, Li-Jun;Cui, Dai;Wang, Zhi-Xiao;Chen, Huan-Huan;Duan, Yu;Shen, Mei-Ping;Zhang, Zhi-Hong;Wang, Xiao-Dong;Chen, Jia-Wei;Alexander, Erik Karl;Yang, Tao 5921
A large proportion of patients with thyroid nodules in China undergo thyroidectomy in order to get confirmatory histology diagnosis. The financial impact of this modality remains to be investigated. To evaluate rationality of performing thyroidectomy without a routine FNA preoperatively from the economic perspective, we conducted a retrospective, observational study of all archival thyroidectomies with records of cost per stay (CPS), cost per day (CPD) and length of stay (LOS) from 2008 to 2013 in the First Affiliated Hospital of Nanjing Medical University. We compared all the parameters between cancer and non-cancer thyroidectomies. We recruited 6, 140 thyroidectomies with valid records of CPS, CPD and LOS in this period. The CPS of cancer thyroidectomy was significantly higher than non-cancer thyroidectomy. The percentage of cancer thyroidectomy increased from 26.5% to 41.6%. The percentage of annual cost of cancer thyroidectomies rose from 30.2% to 45.2%. The LOS for cancer and non-cancer thyroidectomy decreased while the CPD increased in the past six years. The estimated national cost in 2012 for all thyroidectomies would be USD 1.86 billion with USD 1.09 billion for non-cancer thyroidectomies. We have witnessed great improvement in the healthcare for patients with thyroid nodules in China. However, given limited healthcare resources, currently thyroid FNA for more precise preoperative diagnosis may help to curb the rapidly increasing demand in healthcare costs in the future for nodular thyroid disease in China.Abu-Helalah, Munir;Al-Hanaqta, Motasem;Alshraideh, Hussam;Abdulbaqi, Nada;Hijazeen, Jameel 5927
Introduction: Breast cancer is the most common cancer among Jordanians. Breast cancer patients suffer from several negative consequences after treatment and these include pain, fatigue, sexual problems, appearance and body image concerns, with psychological dysfunction. This could affect the patient quality of life and psychological well-being. To the best of our knowledge, there is no published quantitative data on the quality of life and psychological well-being of breast cancer patients in Jordan. The objective of this study was to obtain such data and assess predictors with calculated scores. Methods: In this cross-sectional study conducted among breast cancer patients in Jordan diagnosed in 2009 and 2010, assessment was performed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), the Breast Module (QLQ-BR23) and the Hospital Anxiety and Depression Scale (HADS). Clinical, demographic and psychosocial indicators that could predict patient quality of life scores were collected. Results: The number of patients interviewed was 236 (mean age=$50.7{\pm}10.7$ years). The mean Global Health score for the QLQ-C30 was$63.7{\pm}20.2$ SD. Among functional scales, "social functioning" scored the highest ($mean=78.1{\pm}28.6$ SD), whereas "emotional functioning" scored the lowest ($mean=59.0{\pm}SD\;33.5$ ). For the QLQ-BR23, the worst scores within the functional scales were for "body image" ($mean=52.1{\pm}36.8$ SD) and "future perspective" ($mean=52.9{\pm}38.5$ SD). The worst symptom was "upset by hair loss" ($mean=69.8{\pm}43.0$ ). The mean HADS scores was$18.{\pm}9.0$ SD. Out of study participants, 53% scored abnormal on the anxiety scale and 45% on the depression scale. Severe depression and severe anxiety were detected among 8% and 14% of study participants, respectively. Statistically significant predictors for individual scores were similar to those reported in published studies, such as the presence of recurrence since baseline, family history of cancer, low educational status, current social problems, extent of the disease, presence of financial difficulties, and employment status. Conclusions and Recommendations: Breast cancer survivors in Jordan have overall good quality of life scores when compared with patients from Western countries. However, their psychological wellbeing is more impaired. There is an urgent need for psychosocial support programs and psychological screening and consultation for breast cancer patients at hospitals of the Ministry of Health in Jordan.Bektas, Murat;Ozturk, Candan;Karatas, Hulya;Bektas, Ilknur 5937
Background: This study was conducted as a descriptive-correlational exercise with the aim of determining the effect of student perceptions of social skills on their pro and con perceptions of smoking. Materials and Methods: The study sample comprised 106 students at$6^{th}$ ,$7^{th}$ and$8^{th}$ grades in three primary schools. The data were collected through socio-demographic data collection form, Social Skill Perception Form and Child Decisional Balance Scale. Data were evaluated by percentage calculation, Student t test and correlation analysis. Results: While the point average of pro perception of smoking of the students with a high point average of social skill perception, was$8.6{\pm}3.1$ , in those with a low social skill perception point average it was$10.7{\pm}4.2$ , the difference being significant(p=0.012). The respective point averages of con perceptions were$26.8{\pm}3.7$ and$23.5{\pm}3.3$ , again significant (p=0.000). While a positive medium level (r=0.410) relationship was determined between the point average of social skill perception and con perception of smoking, a negative low level (r=0.281) relationship was determined with the pro perception of smoking. Conclusions: As the social skill perception point average increases, children's con perceptions of smoking increase and their pro perceptions decrease.Wu, Xue-Yan;Huang, Xin-En;Cao, Jie;Shi, Lin;Xu, Xia;Qian, Zhi-Ying 5941
Purpose: To highlight the potential factors that could predict the response rate of patients with metastatic colorectal cancer (mCRC) treated with pemetrexed combined chemotherapy after first- or second-line chemotherapy using the FOLFOX regimen. Materials and Methods: Between January 2007 and July 2014, 54 patients diagnosed and pathologically-confirmed with advanced colorectal cancer in Jiangsu Cancer Hospital and Research Institute, were enrolled. They received pemetrexed at a dose of$500mg/m^2$ by 10 minute infusion on day 1, repeated every 3 weeks. Doses were modified depending on nadir counts of blood cells. Combined chemotherapeutic agents included irinotecan, lobaplatin, carboplatin, oxaliplatin, gemcitabine, cis-platinum or bevacizumab. Multiple variables (age, sex, hemoglobin, platinum drugs combined, metastasis sites, LDH, ALP, CEA>40 ug/ml) reported earlier were selected. We used logistic regression analysis to evaluate relationships between these and tumor response. Results: On multivariable analysis, we found that age was significant in predicting the responsiveness to pemetrexed (p<0.05) combined with oxaliplatin. We did not find any other factors which were significantly associated with the response rate to chemotherapy with pemetrexed and irinotecan. Conclusions: By multivariate analysis, we found that age had significant impact on the responsiveness of pemetrexed when combined with oxaliplatin. Additional research based on genomic properties of host and tumors are needed to clarify markers for better selection of patients who could benefit from pemetrexed combined chemotherapy.Sun, Jing;Hu, Yi;Wu, Bai-Shou;Wang, Jin-Liang;Tao, Hai-Tao;Zhang, Su-Jie 5945
Objectives: To retrospectively review the safety and clinical efficacy of bevacizumab concomitant with chemotherapy in Chinese patients with advanced non-squamous non-small cell lung cancer (NSNSCLC). Methods: Clinical data for 79 patients with NSNSCLC who received bevacizumab concomitant with chemotherapy in Chinese PLA General Hospital from April 28th 2009 to May 5th 2013 were retrospectively reviewed to analyze the clinical efficacy including disease control rate (DCR), overall response rate (ORR), progression-free survival (PFS), overall survival (OS), the Eastern Cooperative Oncology Group (ECOG) score and the safety. Results: The Eastern Cooperative Oncology Group (ECOG) score was 0-2. By the final cutoff date (June 9, 2013), 54 (68.4%) patients had disease progression and 37 (46.8%) died. The ORR was 32.9% and the DCR was 83.5%. The ORR of the first-, second-, and third- or later-line treatments were 51.4%, 25.0% and 12.5%, while the DCR were 94.3%, 80.0% and 70.8%, respectively. The median OS (mOS) and PFS (mPFS) were 13.5 and 5.83 months, respectively. The mOS of patients with the first-, second-, and third- or later- line treatments were 16.2, 10.9 and 8.30 months, while the mPFS were 7.27, 5.90 and 5.17 months, respectively. Chemotherapy-related adverse events included myelosuppression, vomiting, hepatic dysfunction and renal dysfunction, while the common serious bevacizumab-related adverse events were thromboembolic problems, gastrointestinal perforation and reversible posterior leukoencephalopathy syndrome, which could be well managed. Conclusions: Bevacizumab concomitant with chemotherapy is effective and the related toxicity can be well tolerated in Chinese patients with NSNSCLC.Zhong, Chong;Li, Hui-Dong;Liu, Dong-Yang;Xu, Fa-Bin;Wu, Jian;Lin, Xue-Mei;Guo, Rong-Ping 5951
Background: Traditional Chinese Medicine (TCM) possesses several advantages for treating patients with hepatocellular carcinoma (HCC). The theory of 'Jianpi Huayu Therapy' rooted from 'Jin Kui Yao Lue'is one of the most important therapies in this respect. This study was conducted to investigate the clinical effect and safety of hepatectomy combining with 'Jianpi Huayu Therapy' in the treatment of HCC. Materials and Methods: One hundred and twenty patients with HCC were randomized allocated into hepatectomy combined with 'Jianpi Huayu Therapy' group (treatment group, n=60) and hepatectomy alone group (control group, n=60). Disease- free survival (DFS) and overall survival (OS) were the primary end-points. Liver function at the end of one week after surgery, complications, average days of hospitalization as well as performance status (PS) at the end of one month post operation were also compared. Results: No significant differences existed between two groups on baseline analysis (p>0.05). No treatment related mortality occurred in either group. Post-operative complications were detected among 14 patients (23.3%) in the treatment group, and 12 (20.0%) in the control group (p=0.658). Alanine aminotransferase (ALT) at the end of one week after operation was lower in the treatment than control groups (p=0.042). No significant differences in other indexes of liver function were discovered between two groups. Average days of hospitalization reduced by 0.9 day in treatment group than in control (p=0.034). During follow-up, 104 patients (86.6%) developed recurrence. The rates of 1-, 3-, and 5-year DFS and median DFS for all patients were 77.4%, 26.3%, 9.0% and 25.6 months (range, 6.0~68.0), respectively (78.2%, 29.2%, 14.3% and 28.7 months for the 48 patients in the treatment group and 75.0%, 23.3%, 6.4%, and 22.6 months for the 56 patients in the control group (p=0.045)). 101 patients had died at the time of censor, with 1-, 3-, and 5-year overall survival rates and median survival for all patients of 97.5%, 76.4%, 40.5% and 51.2 months (range, 10.0~72.0), respectively (98.3%, 78.0%, 43.6% and 52.6 months, for treatment and 96.7%, 74.7%, 37.4%, and 49.8 months, for controls, respectively (p=0.048)). Conclusions: Hepatectomy combined with 'Jianpi Huayu therapy'was effective in the treatment of HCC, and reduced post-operative recurrence and metastasis and improved DFS and OS of HCC patients.Sulaiman, Suhaina;Shahril, Mohd Razif;Wafa, Sharifah Wajihah;Shaharudin, Soraya Hanie;Hussin, Sharifah Noor Akmal Syed 5959
Background: Dietary carbohydrate, fiber and sugar intake has been shown to play a role in the etiology of breast cancer, but the findings have been inconsistent and limited to developed countries with higher cancer incidence. Objective: To examine the association of premenopausal and postmenopausal breast cancer risk with dietary carbohydrate, fiber and sugar intake. Materials and Methods: This population based case-control study was conducted in Malaysia with 382 breast cancer patients and 382 controls. Food intake pattern was assessed via an interviewer-administered food frequency questionnaire. Logistic regression was used to compute odds ratios (OR) with 95% confidence intervals (CI) and a broad range of potential confounders were included in analysis. Results: A significant two fold increased risk of breast cancer among premenopausal (OR$Q_4$ to$Q_1$ =1.93, 95%CI: 1.53-2.61, p-trend=0.001) and postmenopausal (OR$Q_4$ to$Q_1$ =1.87, 95%CI: 1.03-2.61, p-trend=0.045) women was observed in the highest quartile of sugar. A higher intake of dietary fiber was associated with a significantly lower breast cancer risk among both premenopausal ($ORQ_4$ to$Q_1$ =0.31, 95%CI: 0.12-0.79, p-trend=0.009) and postmenopausal ($ORQ_4$ to$Q_1$ =0.23, 95%CI: 0.07-0.76, p-trend=0.031) women. Conclusions: Sugar and dietary fiber intake were independently related to pre- and postmenopausal breast cancer risk. However, no association was observed for dietary carbohydrate intake.
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