Estimating cancer risks to adults undergoing body CT examinations

International Nuclear Information System (INIS)

Huda, W.; He, W.

2012-01-01

The purpose of the study is to estimate cancer risks from the amount of radiation used to perform body computed tomography (CT) examination. The ImPACT CT Patient Dosimetry Calculator was used to compute values of organ doses for adult body CT examinations. The radiation used to perform each examination was quantified by the dose-length product (DLP). Patient organ doses were converted into corresponding age and sex dependent cancer risks using data from BEIR VII. Results are presented for cancer risks per unit DLP and unit effective dose for 11 sensitive organs, as well as estimates of the contribution from 'other organs'. For patients who differ from a standard sized adult, correction factors based on the patient weight and antero-posterior dimension are provided to adjust organ doses and the corresponding risks. At constant incident radiation intensity, for CT examinations that include the chest, risks for females are markedly higher than those for males, whereas for examinations that include the pelvis, risks in males were slightly higher than those in females. In abdominal CT scans, risks for males and female patients are very similar. For abdominal CT scans, increasing the patient age from 20 to 80 resulted in a reduction in patient risks of nearly a factor of 5. The average cancer risk for chest/abdomen/pelvis CT examinations was ∼26 % higher than the cancer risk caused by 'sensitive organs'. Doses and radiation risks in 80 kg adults were ∼10 % lower than those in 70 kg patients. Cancer risks in body CT can be estimated from the examination DLP by accounting for sex, age, as well as patient physical characteristics. (authors)

Cancer Communication on Social Media: Examining How Cancer Caregivers Use Facebook for Cancer-Related Communication.

Science.gov (United States)

Gage-Bouchard, Elizabeth A; LaValley, Susan; Mollica, Michelle; Beaupin, Lynda Kwon

Americans are increasingly using social media (such as Facebook, YouTube, and Twitter) for health-related communication. Much of the previous research on social media and health communication has focused on Facebook groups related to a specific disease or Facebook pages related to an advocacy organization. Less is known about how people communicate about cancer on personal Facebook pages. In this study, we expand upon previous research by examining how cancer caregivers use personal Facebook pages for cancer-related communication. We examined themes in cancer-related exchanges through a content analysis of 12 months of data from 18 publically available Facebook pages hosted by parents of children with acute lymphoblastic leukemia (15 852 total posts). Six themes emerged: (1) documenting the cancer journey, (2) sharing emotional strain associated with caregiving, (3) promoting awareness and advocacy about pediatric cancer, (4) fundraising, (5) mobilizing support, and (6) expressing gratitude for support. Building upon previous research documenting the increasing use of social media for health-related communication and support, our findings show that personal Facebook pages offer a platform for cancer caregivers to share their cancer-related experiences, promote advocacy and awareness, and mobilize social support. Providers must recognize the importance of social media as a vehicle for support and communication for families of children with cancer. Nurses should educate parents on how to appraise information obtained through Facebook using evidence-based guidelines. Providers can encourage caregivers to use Facebook as a tool for communication, information, and support.

P-MartCancer-Interactive Online Software to Enable Analysis of Shotgun Cancer Proteomic Datasets.

Science.gov (United States)

Webb-Robertson, Bobbie-Jo M; Bramer, Lisa M; Jensen, Jeffrey L; Kobold, Markus A; Stratton, Kelly G; White, Amanda M; Rodland, Karin D

2017-11-01

P-MartCancer is an interactive web-based software environment that enables statistical analyses of peptide or protein data, quantitated from mass spectrometry-based global proteomics experiments, without requiring in-depth knowledge of statistical programming. P-MartCancer offers a series of statistical modules associated with quality assessment, peptide and protein statistics, protein quantification, and exploratory data analyses driven by the user via customized workflows and interactive visualization. Currently, P-MartCancer offers access and the capability to analyze multiple cancer proteomic datasets generated through the Clinical Proteomics Tumor Analysis Consortium at the peptide, gene, and protein levels. P-MartCancer is deployed as a web service (https://pmart.labworks.org/cptac.html), alternatively available via Docker Hub (https://hub.docker.com/r/pnnl/pmart-web/). Cancer Res; 77(21); e47-50. ©2017 AACR . ©2017 American Association for Cancer Research.

Peptidomimetic inhibitors of APC-Asef interaction block colorectal cancer migration.

Science.gov (United States)

Jiang, Haiming; Deng, Rong; Yang, Xiuyan; Shang, Jialin; Lu, Shaoyong; Zhao, Yanlong; Song, Kun; Liu, Xinyi; Zhang, Qiufen; Chen, Yu; Chinn, Y Eugene; Wu, Geng; Li, Jian; Chen, Guoqiang; Yu, Jianxiu; Zhang, Jian

2017-09-01

The binding of adenomatous polyposis coli (APC) to its receptor Asef relieves the negative intramolecular regulation of Asef and leads to aberrant cell migration in human colorectal cancer. Because of its crucial role in metastatic dissemination, the interaction between APC and Asef is an attractive target for anti-colorectal-cancer therapy. We rationally designed a series of peptidomimetics that act as potent inhibitors of the APC interface. Crystal structures and biochemical and cellular assays showed that the peptidomimetics in the APC pocket inhibited the migration of colorectal cells by disrupting APC-Asef interaction. By using the peptidomimetic inhibitor as a chemical probe, we found that CDC42 was the downstream GTPase involved in APC-stimulated Asef activation in colorectal cancer cells. Our work demonstrates the feasibility of exploiting APC-Asef interaction to regulate the migration of colorectal cancer cells, and provides what to our knowledge is the first class of protein-protein interaction inhibitors available for the development of cancer therapeutics targeting APC-Asef signaling.

Interactions among genes, tumor biology and the environment in cancer health disparities: examining the evidence on a national and global scale.

Science.gov (United States)

Wallace, Tiffany A; Martin, Damali N; Ambs, Stefan

2011-08-01

Cancer incidence and mortality rates show great variations across nations and between population groups. These variations are largely explained by differences in age distribution, diet and lifestyle, access to health care, cultural barriers and exposure to carcinogens and pathogens. Cancers caused by infections are significantly more common in developing than developed countries, and they overproportionally affect immigrant populations in the USA and other countries. The global pattern of cancer is not stagnant. Instead, it is dynamic because of fluctuations in the age distribution of populations, improvements in cancer prevention and early detection in affluent countries and rapid changes in diet and lifestyle in parts of the world. For example, increased smoking rates have caused tobacco-induced cancers to rise in various Asian countries, whereas reduced smoking rates have caused these cancers to plateau or even begin to decline in Western Europe and North America. Some population groups experience a disproportionally high cancer burden. In the USA and the Caribbean, cancer incidence and mortality rates are excessively high in populations of African ancestry when compared with other population groups. The causes of this disparity are multifaceted and may include tumor biological and genetic factors and their interaction with the environment. In this review, we will discuss the magnitude and causes of global cancer health disparities and will, with a focus on African-Americans and selected cancer sites, evaluate the evidence that genetic and tumor biological factors contribute to existing cancer incidence and outcome differences among population groups in the USA.

Determinants of a GP visit and cervical cancer screening examination in Great Britain.

Directory of Open Access Journals (Sweden)

Alexander Michael Labeit

Full Text Available In the UK, women are requested to attend a cervical cancer test every 3 years as part of the NHS Cervical Screening Programme. This analysis compares the determinants of a cervical cancer screening examination with the determinants of a GP visit in the same year and investigates if cervical cancer screening participation is more likely for women who visit their GP.A recursive probit model was used to analyse the determinants of GP visits and cervical cancer screening examinations. GP visits were considered to be endogenous in the cervical cancer screening examination. The analysed sample consisted of 52,551 observations from 8,386 women of the British Household Panel Survey.The analysis showed that a higher education level and a worsening self-perceived health status increased the probability of a GP visit, whereas smoking decreased the probability of a GP visit. GP visits enhanced the uptake of a cervical cancer screening examination in the same period. The only variables which had the same positive effect on both dependent variables were higher education and living with a partner. The probability of a cervical cancer screening examination increased also with previous cervical cancer screening examinations and being in the recommended age groups. All other variables had different results for the uptake of a GP visit or a cervical cancer screening examination.Most of the determinants of visiting a GP and cervical cancer screening examination differ from each other and a GP visit enhances the uptake of a smear test.

Identification of the Interaction between P-Glycoprotein and Anxa2 in Multidrug-resistant Human Breast Cancer Cells

International Nuclear Information System (INIS)

Zhang, Hai-chang; Zhang, Fei; Wu, Bing; Han, Jing-hua; Ji, Wei; Zhou, Yan; Niu, Rui-fang

2012-01-01

To explore the interaction of Anxa2 with P-Glycoprotein (P-gp) in the migration and invasion of the multidrug-resistant (MDR) human breast cancer cell line MCF-7/ADR. A pair of short hairpin RNA (shRNA) targeting P-gp was transfected into MCF-7/ADR cells, and monoclonal cell strains were screened. The expression of P-gp was detected by Western blot. Transwell chambers were used to observe the cell migration capacity and invasion ability. The interaction between P-gp and Anxa2 was examined by immunoprecipitation and immunofluorescence confocal microscopy analyses. P-gp expression was significantly knocked down, and there were notable decreasing trends in the migration and invasion capability of MDR breast cancer cells (P<0.05). There was a close interaction between Anxa2 and P-gp. MCF-7/ADR is an MDR human breast cancer cell line with high migration and invasion abilities. The knockdown of P-gp notably impaired the migration and invasion abilities of the tumor cells. The interaction of Anxa2 with P-pg may play an important role in the enhanced invasiveness of MDR human breast cancer cells

Identification of CEA-interacting proteins in colon cancer cells and their changes in expression after irradiation

Energy Technology Data Exchange (ETDEWEB)

Yoo, Byong Chul [Colorectal Cancer Branch, Research Institute, National Cancer Center, Goyang (Korea, Republic of); Yeo, Seung Gu [Dept. of Radiation Oncology, Soonchunhyang University College of Medicine, Soonchunhyang University Hospital, Cheonan (Korea, Republic of)

2017-09-15

The serum carcinoembryonic antigen (CEA) level has been recognized as a prognostic factor in colorectal cancer, and associated with response of rectal cancer to radiotherapy. This study aimed to identify CEA-interacting proteins in colon cancer cells and observe post-irradiation changes in their expression. CEA expression in colon cancer cells was examined by Western blot analysis. Using an anti-CEA antibody or IgG as a negative control, immunoprecipitation was performed in colon cancer cell lysates. CEA and IgG immunoprecipitates were used for liquid chromatography–tandem mass spectrometry (LC-MS/MS) analysis. Proteins identified in the CEA immunoprecipitates but not in the IgG immunoprecipitates were selected as CEA-interacting proteins. After radiation treatment, changes in expression of CEA-interacting proteins were monitored by Western blot analysis. CEA expression was higher in SNU-81 cells compared with LoVo cells. The membrane localization of CEA limited the immunoprecipitation results and thus the number of CEA-interacting proteins identified. Only the Ras-related protein Rab-6B and lysozyme C were identified as CEA-interacting proteins in LoVo and SNU-81 cells, respectively. Lysozyme C was detected only in SNU-81, and CEA expression was differently regulated in two cell lines; it was down-regulated in LoVo but up-regulated in SNU-81 in radiation dosage-dependent manner. CEA-mediated radiation response appears to vary, depending on the characteristics of individual cancer cells. The lysozyme C and Rab subfamily proteins may play a role in the link between CEA and tumor response to radiation, although further studies are needed to clarify functional roles of the identified proteins.

Identification of CEA-interacting proteins in colon cancer cells and their changes in expression after irradiation

International Nuclear Information System (INIS)

Yoo, Byong Chul; Yeo, Seung Gu

2017-01-01

The serum carcinoembryonic antigen (CEA) level has been recognized as a prognostic factor in colorectal cancer, and associated with response of rectal cancer to radiotherapy. This study aimed to identify CEA-interacting proteins in colon cancer cells and observe post-irradiation changes in their expression. CEA expression in colon cancer cells was examined by Western blot analysis. Using an anti-CEA antibody or IgG as a negative control, immunoprecipitation was performed in colon cancer cell lysates. CEA and IgG immunoprecipitates were used for liquid chromatography–tandem mass spectrometry (LC-MS/MS) analysis. Proteins identified in the CEA immunoprecipitates but not in the IgG immunoprecipitates were selected as CEA-interacting proteins. After radiation treatment, changes in expression of CEA-interacting proteins were monitored by Western blot analysis. CEA expression was higher in SNU-81 cells compared with LoVo cells. The membrane localization of CEA limited the immunoprecipitation results and thus the number of CEA-interacting proteins identified. Only the Ras-related protein Rab-6B and lysozyme C were identified as CEA-interacting proteins in LoVo and SNU-81 cells, respectively. Lysozyme C was detected only in SNU-81, and CEA expression was differently regulated in two cell lines; it was down-regulated in LoVo but up-regulated in SNU-81 in radiation dosage-dependent manner. CEA-mediated radiation response appears to vary, depending on the characteristics of individual cancer cells. The lysozyme C and Rab subfamily proteins may play a role in the link between CEA and tumor response to radiation, although further studies are needed to clarify functional roles of the identified proteins

Mouth self-examination in a population at risk of oral cancer.

Science.gov (United States)

Jornet, P López; Garcia, F J Gómez; Berdugo, M Lucero; Perez, F Parra; Lopez, A Pons-Fuster

2015-03-01

Cancer of the oral cavity is a public health problem and many cases are not diagnosed until the disease has reached an advanced stage. The aim of this study was to initiate an educational programme in self-examination for patients at risk from oral cancer. This quasi-experimental study set out to initiate an educational programme in self-examination for patients at risk from oral cancer, assessing the outcomes after three months. In individual 15-minute face-to-face sessions, patients were given information and training in oral cancer risk factors and then verbal instructions as how to carry out oral self-examination. Three months later, patients were interviewed by telephone and asked if they had carried out self-examination independently at home. The programme was evaluated by means of a health belief model questionnaire on perceived susceptibility (3 items), severity (8 items), benefits (4 items), barriers (8 items) and efficacy (6 items). Eighty-six patients (37 females [43.1%] and 49 males [56.9%]) with a mean age of 58.60±10.7 completed the oral self-examination programme. Logistic regression analysis indicated that patients who felt themselves subject to susceptibility (OR: 0.03 95% CI: 0.0-0.86; poral self-examination are needed to decrease morbidity and mortality from oral cancer. © 2015 Australian Dental Association.

Awareness of breast cancer and breast self-examination among ...

African Journals Online (AJOL)

Awareness of breast cancer and breast self-examination among female undergraduate students in a higher teachers training college in Cameroon. ... Conclusion: Though most students are aware of the existence of breast cancer, their overall knowledge on its risk factors and clinical presentation is insufficient with a ...

Network of microRNAs-mRNAs Interactions in Pancreatic Cancer

Science.gov (United States)

Naderi, Elnaz; Mostafaei, Mehdi; Pourshams, Akram

2014-01-01

Background. MicroRNAs are small RNA molecules that regulate the expression of certain genes through interaction with mRNA targets and are mainly involved in human cancer. This study was conducted to make the network of miRNAs-mRNAs interactions in pancreatic cancer as the fourth leading cause of cancer death. Methods. 56 miRNAs that were exclusively expressed and 1176 genes that were downregulated or silenced in pancreas cancer were extracted from beforehand investigations. MiRNA–mRNA interactions data analysis and related networks were explored using MAGIA tool and Cytoscape 3 software. Functional annotations of candidate genes in pancreatic cancer were identified by DAVID annotation tool. Results. This network is made of 217 nodes for mRNA, 15 nodes for miRNA, and 241 edges that show 241 regulations between 15 miRNAs and 217 target genes. The miR-24 was the most significantly powerful miRNA that regulated series of important genes. ACVR2B, GFRA1, and MTHFR were significant target genes were that downregulated. Conclusion. Although the collected previous data seems to be a treasure trove, there was no study simultaneous to analysis of miRNAs and mRNAs interaction. Network of miRNA-mRNA interactions will help to corroborate experimental remarks and could be used to refine miRNA target predictions for developing new therapeutic approaches. PMID:24895587

Network of microRNAs-mRNAs Interactions in Pancreatic Cancer

Directory of Open Access Journals (Sweden)

Elnaz Naderi

2014-01-01

Full Text Available Background. MicroRNAs are small RNA molecules that regulate the expression of certain genes through interaction with mRNA targets and are mainly involved in human cancer. This study was conducted to make the network of miRNAs-mRNAs interactions in pancreatic cancer as the fourth leading cause of cancer death. Methods. 56 miRNAs that were exclusively expressed and 1176 genes that were downregulated or silenced in pancreas cancer were extracted from beforehand investigations. MiRNA–mRNA interactions data analysis and related networks were explored using MAGIA tool and Cytoscape 3 software. Functional annotations of candidate genes in pancreatic cancer were identified by DAVID annotation tool. Results. This network is made of 217 nodes for mRNA, 15 nodes for miRNA, and 241 edges that show 241 regulations between 15 miRNAs and 217 target genes. The miR-24 was the most significantly powerful miRNA that regulated series of important genes. ACVR2B, GFRA1, and MTHFR were significant target genes were that downregulated. Conclusion. Although the collected previous data seems to be a treasure trove, there was no study simultaneous to analysis of miRNAs and mRNAs interaction. Network of miRNA-mRNA interactions will help to corroborate experimental remarks and could be used to refine miRNA target predictions for developing new therapeutic approaches.

Value of computed tomography as a screening examination of pancreatic cancer

International Nuclear Information System (INIS)

Honda, Hiroshi; Watanabe, Katsushi; Nishikawa, Kiyoshi

1983-01-01

The abdominal CT films of 50 patients were reviewed by ten radiologists to evaluate the role of CT examination in the screening of pancreatic cancer. The 50 patients consisted of 10 with pancreatic cancer, 8 with other pancreatic abnormalities, and 32 with normal pancreas. Ten radiologists were divided into two groups according to their experience in evaluating CT examinations, an experienced group and an unexperienced group, respectively. In the detectability of pancreatic abnormality, the experienced group showed a sensitivity of 72.2% and a specificity of 86.2%. The unexperienced group showed a sensitivity of 70.9% and a specificity of 72.0%. In the detectability of pancreatic cancer, the experienced group showed a sensitivity of 62.0% and a specificity of 83.4%. The unexperienced group showed a sensitivity of 66.0% and a specificity of 81.8%. In the localization of the pancreatic cancer, there was no difference between the two groups. Pancreatic abnormality can be detected with high accuracy, but diagnosis of the nature of pancreatic cancer is difficult. Experience in evaluating CT examinations elevates the detectability of pancreatic abnormality but does not elevate the detectability of pancreatic cancer. These results suggest the difficulty in diagnosis of pancreatic cancer. (author)

Oral and neck examination for early detection of oral cancer--a practical guide.

LENUS (Irish Health Repository)

MacCarthy, Denise

2011-08-01

Cancer of the head and neck region presents a challenge since, unlike other areas of the body, the boundaries are not always easy to delineate. The functional morbidity associated with head and neck cancer and its treatment are considerable. Head and neck cancer is described as cancer of the lip, mouth, tongue, tonsil, pharynx (unspecified), salivary gland, hypopharynx, larynx and other. Oral cancer refers to cancers of the lip, tongue, gingivae, floor of the mouth, palate (hard and soft), maxilla, vestibule and retromolar area up to the anterior pillar of the fauces (tonsil). When patients present with oral cancer, over 60% of them have regional (lymph node) and sometimes distant (metastatic) spread. The overall five-year survival rates for oral cancer average at between 50 and 80%, depending on the stage of the disease, varying from 86% for stage I to 12-16% for stage IV. The incidence of \\'field cancerisation\\'\\/unstable oral epithelium is high (17%), and even after successful treatment our patients need to be monitored for dental care and further disease. Unlike other areas in the body, the oral epithelium is readily accessible for examination and even self-examination. Dentists and dental hygienists are effective clinicians in the examination of the oral cavity for mouth cancer. An oral and neck examination must be part of every dental examination. An examination protocol is suggested here, which is similar to, but more detailed than, the standardised oral examination method recommended by the World Health Organisation, and consistent with those protocols followed by the Centres for Disease Control and Prevention and the National Institutes of Health.

Optimizing prognosis-related key miRNA-target interactions responsible for cancer metastasis.

Science.gov (United States)

Zhao, Hongying; Yuan, Huating; Hu, Jing; Xu, Chaohan; Liao, Gaoming; Yin, Wenkang; Xu, Liwen; Wang, Li; Zhang, Xinxin; Shi, Aiai; Li, Jing; Xiao, Yun

2017-12-12

Increasing evidence suggests that the abnormality of microRNAs (miRNAs) and their downstream targets is frequently implicated in the pathogenesis of human cancers, however, the clinical benefit of causal miRNA-target interactions has been seldom studied. Here, we proposed a computational method to optimize prognosis-related key miRNA-target interactions by combining transcriptome and clinical data from thousands of TCGA tumors across 16 cancer types. We obtained a total of 1,956 prognosis-related key miRNA-target interactions between 112 miRNAs and 1,443 their targets. Interestingly, these key target genes are specifically involved in tumor progression-related functions, such as 'cell adhesion' and 'cell migration'. Furthermore, they are most significantly correlated with 'tissue invasion and metastasis', a hallmark of metastasis, in ten distinct types of cancer through the hallmark analysis. These results implicated that the prognosis-related key miRNA-target interactions were highly associated with cancer metastasis. Finally, we observed that the combination of these key miRNA-target interactions allowed to distinguish patients with good prognosis from those with poor prognosis both in most TCGA cancer types and independent validation sets, highlighting their roles in cancer metastasis. We provided a user-friendly database named miRNATarget (freely available at http://biocc.hrbmu.edu.cn/miRNATar/), which provides an overview of the prognosis-related key miRNA-target interactions across 16 cancer types.

TP53 genetic polymorphisms, interactions with lifestyle factors and lung cancer risk: a case control study in a Chinese population

International Nuclear Information System (INIS)

Li, Yanli; Su, Jia; Cai, Lin; Yu, Shunzhang; Zhang, Zuo-Feng; Mu, Lina; Chang, Shen-Chih; Niu, Rungui; Liu, Li; Crabtree-Ide, Christina R; Zhao, Baoxing; Shi, Jianping; Han, Xiaoyou; Li, Jiawei

2013-01-01

A pathway-based genotyping analysis suggested rs2078486 was a novel TP53 SNP, but very few studies replicate this association. TP53 rs1042522 is the most commonly studied SNP, but very few studies examined its potential interaction with environmental factors in relation to lung cancer risk. This study aims to examine associations between two TP53 single-nucleotide polymorphisms (SNPs) (rs2078486, rs1042522), their potential interaction with environmental factors and risk of lung cancer. A case–control study was conducted in Taiyuan, China. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Multiplicative and additive interactions between TP53 SNPs and lifestyle factors were evaluated. Variant TP53 rs2078486 SNP was significantly associated with elevated lung cancer risk among smokers (OR: 1.70, 95% CI: 1.08 - 2.67) and individuals with high indoor air pollution exposure (OR: 1.51, 95% CI: 1.00-2.30). Significant or borderline significant multiplicative and additive interactions were found between TP53 rs2078486 polymorphism with smoking and indoor air pollution exposure. The variant genotype of TP53 SNP rs1042522 significantly increased lung cancer risk in the total population (OR: 1.57, 95% CI: 1.11-2.21), but there was no evidence of heterogeneity among individuals with different lifestyle factors. This study confirmed that TP53 rs2078486 SNP is potentially a novel TP53 SNP that may affect lung cancer risk. Our study also suggested potential synergetic effects of TP53 rs2078486 SNP with smoking and indoor air pollution exposure on lung cancer risk

Passion in breast cancer survivors: examining links to emotional well-being.

Science.gov (United States)

Burke, Shaunna M; Sabiston, Catherine M; Vallerand, Robert J

2012-11-01

This study (1) identified the activities that breast cancer survivors report as passionate; (2) examined whether levels of passion differed based on the types of passionate activities reported and; (3) examined the association between harmonious and obsessive passion and emotional well-being. Early post-treatment breast cancer survivors (N = 177) reported passionate physical activities as most prevalent, and reported higher harmonious passion scores compared to women reporting relaxing and social leisure activities. Harmonious passion was associated with higher positive affect and lower cancer worry. Obsessive passion was linked to higher negative affect, cancer worry, and posttraumatic growth. Passion is important for enhanced well-being.

Use of Digital Rectal Examination as an Adjunct to Prostate Specific Antigen in the Detection of Clinically Significant Prostate Cancer.

Science.gov (United States)

Halpern, Joshua A; Oromendia, Clara; Shoag, Jonathan E; Mittal, Sameer; Cosiano, Michael F; Ballman, Karla V; Vickers, Andrew J; Hu, Jim C

2018-04-01

Guidelines from the NCCN ® (National Comprehensive Cancer Network®) advocate digital rectal examination screening only in men with elevated prostate specific antigen. We investigated the effect of prostate specific antigen on the association of digital rectal examination and clinically significant prostate cancer in a large American cohort. We evaluated the records of the 35,350 men who underwent digital rectal examination in the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial for the development of clinically significant prostate cancer (Gleason 7 or greater). Followup was 343,273 person-years. The primary outcome was the rate of clinically significant prostate cancer among men with vs without suspicious digital rectal examination. We performed competing risks regression to evaluate the interaction between time varying suspicious digital rectal examination and prostate specific antigen. A total of 1,713 clinically significant prostate cancers were detected with a 10-year cumulative incidence of 5.9% (95% CI 5.6-6.2). Higher risk was seen for suspicious vs nonsuspicious digital rectal examination. Increases in absolute risk were small and clinically irrelevant for normal (less than 2 ng/ml) prostate specific antigen (1.5% vs 0.7% risk of clinically significant prostate cancer at 10 years), clinically relevant for elevated (3 ng/ml or greater) prostate specific antigen (23.0% vs 13.7%) and modestly clinically relevant for equivocal (2 to 3 ng/ml) prostate specific antigen (6.5% vs 3.5%). Digital rectal examination demonstrated prognostic usefulness when prostate specific antigen was greater than 3 ng/ml, limited usefulness for less than 2 ng/ml and marginal usefulness for 2 to 3 ng/ml. These findings support the restriction of digital rectal examination to men with higher prostate specific antigen as a reflex test to improve specificity. It should not be used as a primary screening modality to improve sensitivity. Copyright �

Efficient examination to detect the location of cancer in cases with positive sputum cytology

International Nuclear Information System (INIS)

Moriya, Hiroshi; Yaginuma, Koji; Shibuya, Hiroko

1993-01-01

In order to localize cancers in 55 cases with positive sputum cytology, we examined chest CT and otolaryngeal findings, in addition to performing bronchoscopic examinations. Consequently, 30 cases had lung cancer, 5 had laryngopharyngeal cancer and 3 had cancer of the oral cavity. Otolaryngeal observation was useful for detection of these cancers of the upper respiratory tract. In 30 lung cancers, 23 were roentgenographically occult cancers. But, among these 23, 12 had positive findings on chest CT. CT was useful for the cases of roentgenographically occult lung cancer. Especially, CT was very effective for detection of small cancer lesions in the peripheral lung, which were undetectable bronchofiberscopically. Three of 20 cases, in which no cancers were detected after the initial examination, had cancer lesions 1-2 years later. These results suggest that CT, otolaryngeal observation and intensive follow-up of undetectable cases are useful for localizing cancer in cases with positive sputum cytology. (author)

Genome-wide diet-gene interaction analyses for risk of colorectal cancer.

Directory of Open Access Journals (Sweden)

Jane C Figueiredo

2014-04-01

Full Text Available Dietary factors, including meat, fruits, vegetables and fiber, are associated with colorectal cancer; however, there is limited information as to whether these dietary factors interact with genetic variants to modify risk of colorectal cancer. We tested interactions between these dietary factors and approximately 2.7 million genetic variants for colorectal cancer risk among 9,287 cases and 9,117 controls from ten studies. We used logistic regression to investigate multiplicative gene-diet interactions, as well as our recently developed Cocktail method that involves a screening step based on marginal associations and gene-diet correlations and a testing step for multiplicative interactions, while correcting for multiple testing using weighted hypothesis testing. Per quartile increment in the intake of red and processed meat were associated with statistically significant increased risks of colorectal cancer and vegetable, fruit and fiber intake with lower risks. From the case-control analysis, we detected a significant interaction between rs4143094 (10p14/near GATA3 and processed meat consumption (OR = 1.17; p = 8.7E-09, which was consistently observed across studies (p heterogeneity = 0.78. The risk of colorectal cancer associated with processed meat was increased among individuals with the rs4143094-TG and -TT genotypes (OR = 1.20 and OR = 1.39, respectively and null among those with the GG genotype (OR = 1.03. Our results identify a novel gene-diet interaction with processed meat for colorectal cancer, highlighting that diet may modify the effect of genetic variants on disease risk, which may have important implications for prevention.

Identifying functional cancer-specific miRNA-mRNA interactions in testicular germ cell tumor.

Science.gov (United States)

Sedaghat, Nafiseh; Fathy, Mahmood; Modarressi, Mohammad Hossein; Shojaie, Ali

2016-09-07

Testicular cancer is the most common cancer in men aged between 15 and 35 and more than 90% of testicular neoplasms are originated at germ cells. Recent research has shown the impact of microRNAs (miRNAs) in different types of cancer, including testicular germ cell tumor (TGCT). MicroRNAs are small non-coding RNAs which affect the development and progression of cancer cells by binding to mRNAs and regulating their expressions. The identification of functional miRNA-mRNA interactions in cancers, i.e. those that alter the expression of genes in cancer cells, can help delineate post-regulatory mechanisms and may lead to new treatments to control the progression of cancer. A number of sequence-based methods have been developed to predict miRNA-mRNA interactions based on the complementarity of sequences. While necessary, sequence complementarity is, however, not sufficient for presence of functional interactions. Alternative methods have thus been developed to refine the sequence-based interactions using concurrent expression profiles of miRNAs and mRNAs. This study aims to find functional cancer-specific miRNA-mRNA interactions in TGCT. To this end, the sequence-based predicted interactions are first refined using an ensemble learning method, based on two well-known methods of learning miRNA-mRNA interactions, namely, TaLasso and GenMiR++. Additional functional analyses were then used to identify a subset of interactions to be most likely functional and specific to TGCT. The final list of 13 miRNA-mRNA interactions can be potential targets for identifying TGCT-specific interactions and future laboratory experiments to develop new therapies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Rationale for promoting physical activity among cancer survivors: literature review and epidemiologic examination.

Science.gov (United States)

Loprinzi, Paul D; Lee, Hyo

2014-03-01

To review the extant literature on the link between physical activity and health outcomes among cancer survivors; identify evidence-based strategies to promote physical activity among this population; and conduct an epidemiologic study based on gaps from the literature review, examining the association between physical activity and various biologic markers. The authors used PubMed and Google Scholar up to July 2013, as well as data from the 2003-2006 National Health and Nutrition Examination Survey for the empirical study. Studies were examined through a systematic review process. In the epidemiologic study, 227 adult cancer survivors wore an accelerometer for four days or longer, with biologic markers (e.g., cholesterol) assessed from a blood sample. The review study demonstrated that cancer survivors are relatively inactive, but physical activity may help to reduce the risk of cancer recurrence and cancer-related mortality, increase cancer treatment rates, reduce pain and other side effects associated with cancer treatment, and improve physical and mental health. The epidemiologic study showed that physical activity was associated with several understudied biomarkers (e.g., neutrophils, white blood cells) that are linked with cancer recurrence, cancer-related mortality, and other chronic diseases. Nurses are encouraged to promote physical activity in cancer survivors.

Digital rectal examination for prostate cancer: Attitude and ...

African Journals Online (AJOL)

Digital rectal examination for prostate cancer: Attitude and experience of final ... based study of final year medical students two months to graduation carried out ... Results: There were 100 students in the study, with a male: female ratio of 3.6:1.

A comparative study on radiological and endoscopic examinations of the stomach cancer

Energy Technology Data Exchange (ETDEWEB)

Lee, Jung Sook; Lee, Yong Chul; Kim, Han Suk [National Medical Center, Seoul (Korea, Republic of)

1985-12-15

An analysis was done for the diagnostic accuracy of radiological and endoscopic examinations in 132 cases of the histologically proved stomach cancer at the national Medical Center from Jan. 1975 to Jan. 1979. The problem in radiological misdiagnosis was especially discussed aimed to improve the further diagnostic accuracy. The following results were obtained: 1. The incidence of the stomach cancer was higher in male than that of female, and was most prevalent in 5th and 6th decades. 2. The misdiagnosis rate of radiological examination of the stomach cancer was 13.5% (18 cases), that of endoscopic examination was 8.3% (11 cases) and that of both examination was 4.6% (6 cases). 3. In most cases of misdiagnosis, the majority were diagnosed as benign gastric ulcer. 4. The causative factors of misdiagnosis in radiological examination were interpretation error in 8 cases and technically poor, unsatisfactory study in 10 cases. 5. In order to decrease the misdiagnosis rate, standardization of radiological examination and careful interpretation are necessary. 6. Complementary examinations of radiology and endoscopy can decrease the misdiagnosis rate.

Targeting AR Variant-Coactivator Interactions to Exploit Prostate Cancer Vulnerabilities.

Science.gov (United States)

Magani, Fiorella; Peacock, Stephanie O; Rice, Meghan A; Martinez, Maria J; Greene, Ann M; Magani, Pablo S; Lyles, Rolando; Weitz, Jonathan R; Burnstein, Kerry L

2017-11-01

Castration-resistant prostate cancer (CRPC) progresses rapidly and is incurable. Constitutively active androgen receptor splice variants (AR-Vs) represent a well-established mechanism of therapeutic resistance and disease progression. These variants lack the AR ligand-binding domain and, as such, are not inhibited by androgen deprivation therapy (ADT), which is the standard systemic approach for advanced prostate cancer. Signaling by AR-Vs, including the clinically relevant AR-V7, is augmented by Vav3, an established AR coactivator in CRPC. Using mutational and biochemical studies, we demonstrated that the Vav3 Diffuse B-cell lymphoma homology (DH) domain interacted with the N-terminal region of AR-V7 (and full length AR). Expression of the Vav3 DH domain disrupted Vav3 interaction with and enhancement of AR-V7 activity. The Vav3 DH domain also disrupted AR-V7 interaction with other AR coactivators: Src1 and Vav2, which are overexpressed in PC. This Vav3 domain was used in proof-of-concept studies to evaluate the effects of disrupting the interaction between AR-V7 and its coactivators on CRPC cells. This disruption decreased CRPC cell proliferation and anchorage-independent growth, caused increased apoptosis, decreased migration, and resulted in the acquisition of morphological changes associated with a less aggressive phenotype. While disrupting the interaction between FL-AR and its coactivators decreased N-C terminal interaction, disrupting the interaction of AR-V7 with its coactivators decreased AR-V7 nuclear levels. Implications: This study demonstrates the potential therapeutic utility of inhibiting constitutively active AR-V signaling by disrupting coactivator binding. Such an approach is significant, as AR-Vs are emerging as important drivers of CRPC that are particularly recalcitrant to current therapies. Mol Cancer Res; 15(11); 1469-80. ©2017 AACR . ©2017 American Association for Cancer Research.

Strategy for improving the detailed examination rate for colorectal cancer screening. New approach for detailed colorectal cancer examination. Study for optimal pre-treatment for CT colonography

International Nuclear Information System (INIS)

Mitsushima, Toru; Fujiwara, Masanori; Nagata, Koichi

2012-01-01

In order to drastically improve the detailed examination rate for strategic colorectal cancer examination in Japan, it is necessary to introduce CT colonography (CTC) as a detailed examination method for colorectal cancer examination, in addition to colonoscopy (CS) which is the conventional detailed examination method. In our study, a cleansing enema/contrast solution (3% Nif-C) was prepared by adding 60 ml of a water-soluble iodine-based contrast agent (Gastrografin) and water to an oral cleansing enema agent (Niflec) in solid (powder) form to a final amount of 2000 ml. The solution was compared with a Niflec solution. In terms of patient's acceptability, more than half of the examined patients answered ''easier to drink than the Niflec solution'' or ''as easy to drink as the Niflec solution. '' Also, the Nif-C solution was comparable or superior to the Niflec solution in terms of cleansing enema effects. Regarding imaging effects essential for CTC, the CT level was found to be 200 HU or greater for any large intestine region upon CTC using the Nif-C solution. Thus, practically sufficient imaging effects were achieved. In conclusion, CTC with pretreatment involving a cleansing enema with oral administration of 3% Nif-C is superior to CS in terms of patient's acceptability. In addition, at least in view of the overseas reports on CTC, there is no particular problem in terms of diagnostic accuracy. Thus, CTC is expected to resolve various problems related to colorectal cancer examination in Japan. (author)

Attitudes Toward Testicular Cancer and Self-Examination Among Northern Irish Males.

Science.gov (United States)

Roy, Rachel Kathryn; Casson, Karen

2017-03-01

Testicular cancer incidence rates are increasing worldwide making it the most common malignancy in males aged 15 to 45 years. Without a known way to prevent the disease health professionals must promote awareness and early detection. A literature review identified a scarcity of information regarding awareness and knowledge of, and attitudes toward, testicular cancer and testicular self-examination among men in Northern Ireland. This study aimed to establish baseline data for Northern Ireland using a convenience sample of 150 men, aged 18 to 45 years. The sample was recruited from across the country and so represents a range of education and area deprivation levels. An online survey was used to collect data. Results showed that while 39% of respondents correctly identified the age group at highest risk for testicular cancer, only 17% of respondents had ever heard of a testicular self-examination. Analysis revealed knowledge, awareness, and attitudes differed by age groups and area deprivation quintiles. It is recommended that health promoters in Northern Ireland and elsewhere use these findings to tailor health promotion initiatives to engage men and raise testicular cancer and self-examination awareness.

Cell-ECM Interactions During Cancer Invasion

Science.gov (United States)

Jiang, Yi

The extracellular matrix (ECM), a fibrous material that forms a network in a tissue, significantly affects many aspects of cellular behavior, including cell movement and proliferation. Transgenic mouse tumor studies indicate that excess collagen, a major component of ECM, enhances tumor formation and invasiveness. Clinically, tumor associated collagen signatures are strong markers for breast cancer survival. However, the underlying mechanisms are unclear since the properties of ECM are complex, with diverse structural and mechanical properties depending on various biophysical parameters. We have developed a three-dimensional elastic fiber network model, and parameterized it with in vitro collagen mechanics. Using this model, we study ECM remodeling as a result of local deformation and cell migration through the ECM as a network percolation problem. We have also developed a three-dimensional, multiscale model of cell migration and interaction with ECM. Our model reproduces quantitative single cell migration experiments. This model is a first step toward a fully biomechanical cell-matrix interaction model and may shed light on tumor associated collagen signatures in breast cancer. This work was partially supported by NIH-U01CA143069.

Goal adjustment strategies operationalised and empirically examined in adolescents with cancer

NARCIS (Netherlands)

Janse, Moniek; Sulkers, Esther; Tissing, Wim J. E.; Sanderman, Robbert; Sprangers, Mirjam A. G.; Ranchor, Adelita V.; Fleer, Joke

Adolescents facing cancer may need to adjust their personal life goals. Theories identified several goal adjustment strategies, but their use has not been tested. Therefore, this study operationalises goal adjustment strategies and examines their use. Adolescent cancer patients listed their goals 3

Imbalanced Nutrient Intake in Cancer Survivors from the Examination from the Nationwide Health Examination Center-Based Cohort

Directory of Open Access Journals (Sweden)

Boyoung Park

2018-02-01

Full Text Available This study was conducted to examine the nutrient intake status of cancer survivors. A total of 5224 cancer survivors, 19,926 non-cancer individuals without comorbidities (non-cancer I, and 20,622 non-cancer individuals with comorbidities, matched by age, gender, and recruitment center location were included in the analysis. Generally, the proportion of total energy from carbohydrates was higher and the proportion from fat was lower in cancer survivors. The odds ratios (ORs for total energy (OR = 0.92, 95% confidence interval (CI = 0.86–0.99, proportion of total energy from fat (OR = 0.54, 95% CI = 0.35–0.83, and protein (OR = 0.85, 95% CI = 0.79–0.90 were significantly lower, and the OR for the proportion of total energy from carbohydrates was higher (OR = 1.21, 95% CI = 1.10–1.33 in the cancer survivors than in non-cancer I. Additionally, the cancer survivors’ protein, vitamin B1, vitamin B2, niacin, and phosphorus intakes were lower, whereas their vitamin C intake was higher. When divided by cancer type, the ORs for the carbohydrate percentages were significantly higher in the colon and breast cancer survivors, whereas protein intake was lower in gastric, breast, and cervical cancer survivors. The nutrient intake patterns in Asian cancer survivors are poor, with higher carbohydrate and lower fat and protein intakes.

Interaction patterns between parents with advanced cancer and their adolescent children.

Science.gov (United States)

Sheehan, Denice Kopchak; Draucker, Claire Burke

2011-10-01

Advanced cancer profoundly affects those with the illness and their families. The interaction patterns between parents with advanced cancer and their adolescent children are likely to influence how a family experiences a parent's dying process. There is little information on such interactions. This study aimed to develop an explanatory model that explains interaction patterns between parents with advanced cancer and their adolescent children and to identify strategies to prepare children for their lives after a parent dies. Semi-structured interviews were conducted with 9 parents with advanced cancer, 7 of their spouses/partners, and 10 of their adolescent children. The interviews were recorded, transcribed verbatim, and analyzed using a constructionist grounded theory approach. Twenty-six family participants were interviewed. Their main concern was not having enough time together. In response, they described a four-stage process for optimizing the time they had left together: coming to know our time together is limited, spending more time together, extending our time together, and giving up our time together to end the suffering. The adolescents and their ill parents did not change their interaction patterns until they realized their time together was limited by the advanced cancer. Then they spent more time together to make things easier for each other. Time was of great importance to the parents and adolescents; all the participants structured their stories in relation to the concept of time. The model reflects the dynamic process by which families continuously adapt their relationships in the face of advanced cancer. 2010 John Wiley & Sons, Ltd.

Breast self examination and breast cancer: Knowledge and practice ...

African Journals Online (AJOL)

... within their communities for screening behaviours in health promotion. Medical ... breast self examination (BSE) and breast cancer to be effective health educators. ... female students drawn from schools within the College of Health sciences, ...

Plant cyclopeptide RA-V kills human breast cancer cells by inducing mitochondria-mediated apoptosis through blocking PDK1–AKT interaction

International Nuclear Information System (INIS)

Fang, Xian-Ying; Chen, Wei; Fan, Jun-Ting; Song, Ran; Wang, Lu; Gu, Yan-Hong; Zeng, Guang-Zhi; Shen, Yan; Wu, Xue-Feng; Tan, Ning-Hua; Xu, Qiang; Sun, Yang

2013-01-01

In the present paper, we examined the effects of a natural cyclopeptide RA-V on human breast cancer cells and the underlying mechanisms. RA-V significantly inhibited the growth of human breast cancer MCF-7, MDA-MB-231 cells and murine breast cancer 4T1 cells. In addition, RA-V triggered mitochondrial apoptotic pathway which was indicated by the loss of mitochondrial membrane potential, the release of cytochrome c, and the activation of caspase cascade. Further study showed that RA-V dramatically inhibited phosphorylation of AKT and 3-phosphoinositide dependent protein kinase 1 (PDK1) in MCF-7 cells. Moreover, RA-V disrupted the interaction between PDK1 and AKT in MCF-7 cells. Furthermore, RA-V-induced apoptosis could be enhanced by phosphatidylinositol 3-kinase inhibitor or attenuated by over-expression of AKT in all the three kinds of breast cancer cells. Taken together, this study shows that RA-V, which can induce mitochondria-mediated apoptosis, exerts strong anti-tumor activity against human breast cancer. The underlying anti-cancer mechanism of RA-V is related to the blockage of the interaction between PDK1 and AKT. - Highlights: ► Plant cyclopeptide RA-V kills human breast cancer cells. ► RA-V triggered mitochondrial apoptotic pathway in human breast cancer cells. ► RA-V inhibited phosphorylation of AKT and PDK1 in breast cancer MCF-7 cells. ► Its mechanism is related to the blockage of the interaction between PDK1 and AKT

Plant cyclopeptide RA-V kills human breast cancer cells by inducing mitochondria-mediated apoptosis through blocking PDK1–AKT interaction

Energy Technology Data Exchange (ETDEWEB)

Fang, Xian-Ying; Chen, Wei [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing (China); Fan, Jun-Ting [State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming (China); Song, Ran; Wang, Lu [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing (China); Gu, Yan-Hong [Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing (China); Zeng, Guang-Zhi [State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming (China); Shen, Yan; Wu, Xue-Feng [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing (China); Tan, Ning-Hua, E-mail: nhtan@mail.kib.ac.cn [State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming (China); Xu, Qiang, E-mail: molpharm@163.com [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing (China); Sun, Yang, E-mail: yangsun@nju.edu.cn [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing (China)

2013-02-15

In the present paper, we examined the effects of a natural cyclopeptide RA-V on human breast cancer cells and the underlying mechanisms. RA-V significantly inhibited the growth of human breast cancer MCF-7, MDA-MB-231 cells and murine breast cancer 4T1 cells. In addition, RA-V triggered mitochondrial apoptotic pathway which was indicated by the loss of mitochondrial membrane potential, the release of cytochrome c, and the activation of caspase cascade. Further study showed that RA-V dramatically inhibited phosphorylation of AKT and 3-phosphoinositide dependent protein kinase 1 (PDK1) in MCF-7 cells. Moreover, RA-V disrupted the interaction between PDK1 and AKT in MCF-7 cells. Furthermore, RA-V-induced apoptosis could be enhanced by phosphatidylinositol 3-kinase inhibitor or attenuated by over-expression of AKT in all the three kinds of breast cancer cells. Taken together, this study shows that RA-V, which can induce mitochondria-mediated apoptosis, exerts strong anti-tumor activity against human breast cancer. The underlying anti-cancer mechanism of RA-V is related to the blockage of the interaction between PDK1 and AKT. - Highlights: ► Plant cyclopeptide RA-V kills human breast cancer cells. ► RA-V triggered mitochondrial apoptotic pathway in human breast cancer cells. ► RA-V inhibited phosphorylation of AKT and PDK1 in breast cancer MCF-7 cells. ► Its mechanism is related to the blockage of the interaction between PDK1 and AKT.

Environmental and genetic interactions in human cancer

International Nuclear Information System (INIS)

Paterson, M.C.

Humans, depending upon their genetic make-up, differ in their susceptibility to the cancer-causing effects of extrinsic agents. Clinical and laboratory studies on the hereditary disorder, ataxia telangiectasia (AT) show that persons afflicted with this are cancer-prone and unusually sensitive to conventional radiotherapy. Their skin cells, when cultured, are hypersensitive to killing by ionizing radiation, being defective in the enzymatic repair of radiation-induced damange to the genetic material, deoxyribonucleic acid (DNA). This molecular finding implicates DNA damage and its imperfect repair as an early step in the induction of human cancer by radiation and other carcinogens. The parents of AT patients are clincally normal but their cultured cells are often moderately radiosensitive. The increased radiosensitivity of cultured cells offers a means of identifying a presumed cancer-prone subpopulation that should avoid undue exposure to certain carcinogens. The radioresponse of cells from patients with other cancer-associated genetic disorders and persons suspected of being genetically predisposed to radiation-induced cancer has also been measured. Increased cell killing by γ-rays appears in the complex genetic disease, tuberous sclerosis. Cells from cancer-stricken members of a leukemia-prone family are also radiosensitive, as are cells from one patient with radiation-associated breast cancer. These radiobiological data, taken together, strongly suggest that genetic factors can interact with extrinsic agents and thereby play a greater causative role in the development of common cancers in man than previously thought. (L.L.)

Personalized Nutrition-Genes, Diet, and Related Interactive Parameters as Predictors of Cancer in Multiethnic Colorectal Cancer Families.

Science.gov (United States)

Shiao, S Pamela K; Grayson, James; Lie, Amanda; Yu, Chong Ho

2018-06-20

To personalize nutrition, the purpose of this study was to examine five key genes in the folate metabolism pathway, and dietary parameters and related interactive parameters as predictors of colorectal cancer (CRC) by measuring the healthy eating index (HEI) in multiethnic families. The five genes included methylenetetrahydrofolate reductase ( MTHFR ) 677 and 1298, methionine synthase ( MTR ) 2756, methionine synthase reductase ( MTRR 66), and dihydrofolate reductase ( DHFR ) 19bp , and they were used to compute a total gene mutation score. We included 53 families, 53 CRC patients and 53 paired family friend members of diverse population groups in Southern California. We measured multidimensional data using the ensemble bootstrap forest method to identify variables of importance within domains of genetic, demographic, and dietary parameters to achieve dimension reduction. We then constructed predictive generalized regression (GR) modeling with a supervised machine learning validation procedure with the target variable (cancer status) being specified to validate the results to allow enhanced prediction and reproducibility. The results showed that the CRC group had increased total gene mutation scores compared to the family members ( p < 0.05). Using the Akaike's information criterion and Leave-One-Out cross validation GR methods, the HEI was interactive with thiamine (vitamin B1), which is a new finding for the literature. The natural food sources for thiamine include whole grains, legumes, and some meats and fish which HEI scoring included as part of healthy portions (versus limiting portions on salt, saturated fat and empty calories). Additional predictors included age, as well as gender and the interaction of MTHFR 677 with overweight status (measured by body mass index) in predicting CRC, with the cancer group having more men and overweight cases. The HEI score was significant when split at the median score of 77 into greater or less scores, confirmed through

Public awareness of testicular cancer and testicular self-examination in academic environments: a lost opportunity

Directory of Open Access Journals (Sweden)

Henry A. A. Ugboma

2011-01-01

Full Text Available BACKGROUND: Although testicular cancer is the most common cancer among 18- to 50-year-old males, healthcare providers seldom teach testicular self-examination techniques to clients, thus potentially missing opportunities for early detection. This form of cancer is easily diagnosable by testicular self-examination and is 96% curable if detected early. Periodic self-examination must be performed for early detection. Knowledge deficits and sociocultural norms contribute to low levels of health-related knowledge in most patients, resulting in undue delays before seeking medical advice. OBJECTIVE: Our aim is to assess the level of awareness of testicular cancer and the prevalence of the practice of testicular self-examination in academic environments to enable appropriate interventions. METHOD: A cross-sectional survey was administered to 750 consecutive males aged 18-50 years in three tertiary institutions in Port Harcourt from October 2008 to April 2009. RESULT: Knowledge or awareness of testicular cancer was poor. Almost all of the respondents were unaware that testicular lumps may be signs of cancer. A lump was typically construed as a benign carbuncle or something that could resolve spontaneously. The main factor contributing to respondents' lack of knowledge of testicular cancer was that few reported that they were "ever taught about testicular self-examination." CONCLUSION: Young adult men are unaware of their risk for testicular cancer, which is the most common neoplasm in this age group. Healthcare providers are not informing them of this risk, nor are they teaching them the simple early detection technique of self-examination of the testes.

Beyond Knowledge Gaps: Examining Socioeconomic Differences in Response to Cancer News

Science.gov (United States)

Niederdeppe, Jeff

2008-01-01

This article tested a model, informed by the knowledge gap hypothesis, to predict information seeking about cancer immediately following news about the diagnosis or death from cancer of a national celebrity. I identified five celebrity news events and examined their impact using data from the 2005 Health Information National Trends Survey. News…

Early detection of testicular cancer: revisiting the role of self-efficacy in testicular self-examination among young asymptomatic males.

Science.gov (United States)

Umeh, Kanayo; Chadwick, Rebecca

2016-02-01

Research suggests that self-efficacy is an important factor in behaviors that facilitate the early-detection of various cancers. In general people with high self-efficacy are more likely to attend cancer screening sessions or perform bodily self-exams. However, there is a paucity of research focusing on testicular cancer and testicular self-examination (TSE). The effect of self-efficacy on TSE remains unclear especially given the relative obscurity of the testicular cancer threat, and appropriate clinical- and self-detection procedures, in the young asymptomatic male population. Thus, the present study tested the interaction of self-efficacy with young men's appraisals of the threat of testicular cancer. The study was based on 2 × 2 × 2 mixed factorial experimental design. Over 100 young asymptomatic men were exposed to a health warning about testicular cancer and randomly assigned to high/low self-efficacy, vulnerability, and severity conditions. High self-efficacy increased motivation to perform TSE given high vulnerability, but damaged attitudes to self-exams given low vulnerability and severity estimates. High self-efficacy also facilitated subsequent TSE. Overall, these findings support preexisting notions of self-efficacy but raise new questions about the moderating effects of threat appraisals.

Examination of VDR/RXR/DRIP205 Interaction, Intranuclear Localization, and DNA Binding in Ras-Transformed Keratinocytes and Its Implication for Designing Optimal Vitamin D Therapy in Cancer.

Science.gov (United States)

Jusu, Sylvester; Presley, John F; Williams, Chris; Das, Sanjoy Kumar; Jean-Claude, Bertrand; Kremer, Richard

2018-03-01

Retinoid X receptor (RXR) occupies a central position within the nuclear receptor superfamily, serving as an obligatory partner to numerous other nuclear receptors, including vitamin D receptor (VDR). In the current study, we examined whether phosphorylation of RXRα at serine 260 affects VDR/RXR and VDR interacting protein (DRIP) 205 coactivator recruitment, interactions, and binding of the VDR/human RXRα (hRXRα)/DRIP205 complex to chromatin. Serine 260 is a critical amino acid on the hRXRα that is located in close spatial proximity to regions of coactivator and corepressor interactions. Using fluorescence resonance energy transfer and immunofluorescence studies, we showed that the physical interaction between hRXRα and DRIP205 coactivator was impaired in human keratinocytes with the ras oncogene (HPK1Aras) or transfected with the wild-type hRXRα. Furthermore, the nuclear colocalization of VDR/DRIP205, hRXRα/DRIP205, and VDR/hRXRα/DRIP205 complex binding to chromatin is impaired in the HPK1Aras cells when compared with the normal human keratinocytes (HPK1A cells). However, transfection with the nonphosphorylatable hRXRα (S260A) mutant or treatment with the mitogen-activated protein kinase (MAPK) inhibitor UO126 rescued their nuclear localization, interaction, and binding of the complex to chromatin in the HPK1Aras cells. In summary, we have demonstrated, using highly specific intracellular tagging methods in live and fixed cells, important alterations of the vitamin D signaling system in cancer cells in which the ras-raf-MAPK system is activated, suggesting that specific inhibition of this commonly activated pathway could be targeted therapeutically to enhance vitamin D efficacy. Copyright © 2018 Endocrine Society.

Testicular self-examination and testicular cancer: a cost-utility analysis.

Science.gov (United States)

Aberger, Michael; Wilson, Bradley; Holzbeierlein, Jeffrey M; Griebling, Tomas L; Nangia, Ajay K

2014-12-01

The United States Preventive Services Task Force (USPSTF) has recommended against testicular self-examinations (TSE) or clinical examination for testicular cancer screening. However, in this recommendation there was no consideration of the significant fiscal cost of treating advanced disease versus evaluation of benign disease. In this study, a cost-utility validation for TSE was performed. The cost of treatment for an advanced-stage testicular tumor (both seminomatous and nonseminomatous) was compared to the cost of six other scenarios involving the clinical assessment of a testicular mass felt during self-examination (four benign and two early-stage malignant). Medicare reimbursements were used as an estimate for a national cost standard. The total treatment cost for an advanced-stage seminoma ($48,877) or nonseminoma ($51,592) equaled the cost of 313-330 benign office visits ($156); 180-190 office visits with scrotal ultrasound ($272); 79-83 office visits with serial scrotal ultrasounds and labs ($621); 6-7 office visits resulting in radical inguinal orchiectomy for benign pathology ($7,686) or 2-3 office visits resulting in treatment and surveillance of an early-stage testicular cancer ($17,283: seminoma, $26,190: nonseminoma). A large number of clinical evaluations based on the TSE for benign disease can be made compared to the cost of one missed advanced-stage tumor. An average of 2.4 to 1 cost benefit ratio was demonstrated for early detected testicular cancer versus advanced-stage disease. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Oxidative balance and colon and rectal cancer: interaction of lifestyle factors and genes.

Science.gov (United States)

Slattery, Martha L; Lundgreen, Abbie; Welbourn, Bill; Wolff, Roger K; Corcoran, Christopher

2012-06-01

Pro-oxidant and anti-oxidant genetic and lifestyle factors can contribute to an individual's level of oxidative stress. We hypothesize that diet, lifestyle and genetic factors work together to influence colon and rectal cancer through an oxidative balance mechanism. We evaluated nine markers for eosinophil peroxidase (EPX), two for myeloperoxidase (MPO), four for hypoxia-inducible factor-1A (HIFIA), and 16 for inducible nitric oxide synthase (NOS2A) in conjunction with dietary antioxidants, aspirin/NSAID use, and cigarette smoking. We used data from population-based case-control studies (colon cancer n=1555 cases, 1956 controls; rectal cancer n=754 cases, 959 controls). Only NOS2A rs2297518 was associated with colon cancer (OR 0.86 95% CI 0.74, 0.99) and EPX rs2302313 and MPO rs2243828 were associated with rectal cancer (OR 0.75 95% CI 0.59, 0.96; OR 0.81 95% CI 0.67, 0.99 respectively) for main effects. However, after adjustment for multiple comparisons we observed the following significant interactions for colon cancer: NOS2A and lutein, EPX and aspirin/NSAID use, and NOS2A (4 SNPs) and cigarette smoking. For rectal cancer we observed the following interactions after adjustment for multiple comparisons: HIF1A and vitamin E, NOS2A (3SNPs) with calcium; MPO with lutein; HIF1A with lycopene; NOS2A with selenium; EPX and NOS2A with aspirin/NSAID use; HIF1A, MPO, and NOS2A (3 SNPs) with cigarette smoking. We observed significant interaction between a composite oxidative balance score and a polygenic model for both colon (p interaction 0.0008) and rectal cancer (p=0.0018). These results suggest the need to comprehensively evaluate interactions to assess the contribution of risk from both environmental and genetic factors. Copyright © 2012 Elsevier B.V. All rights reserved.

Modeling mechanical interactions between cancerous mammary acini

Science.gov (United States)

Wang, Jeffrey; Liphardt, Jan; Rycroft, Chris

2015-03-01

The rules and mechanical forces governing cell motility and interactions with the extracellular matrix of a tissue are often critical for understanding the mechanisms by which breast cancer is able to spread through the breast tissue and eventually metastasize. Ex vivo experimentation has demonstrated the the formation of long collagen fibers through collagen gels between the cancerous mammary acini responsible for milk production, providing a fiber scaffolding along which cancer cells can disorganize. We present a minimal mechanical model that serves as a potential explanation for the formation of these collagen fibers and the resultant motion. Our working hypothesis is that cancerous cells induce this fiber formation by pulling on the gel and taking advantage of the specific mechanical properties of collagen. To model this system, we employ a new Eulerian, fixed grid simulation method to model the collagen as a nonlinear viscoelastic material subject to various forces coupled with a multi-agent model to describe individual cancer cells. We find that these phenomena can be explained two simple ideas: cells pull collagen radially inwards and move towards the tension gradient of the collagen gel, while being exposed to standard adhesive and collision forces.

The value of imaging examinations in diagnosis and curative effect evaluation of breast cancer

International Nuclear Information System (INIS)

Xia Xiaotian; Zhang Yongxue

2010-01-01

Breast cancer is a serious impact on women's physical and mental health and a life-threatening common disease. Imaging examinations have great significances in diagnosing and evaluating curative effect on breast cancer. This article aims to introduce and comprehensive the value of diagnosis and curative effect evaluation of breast cancer in the context of imaging examinations (ultrasonography, mammography, breast CT, breast MRI, breast 99 Tc m -MIBI imaging, PET, PET-CT, etc). (authors)

The interaction between informal cancer caregivers and health care professionals

DEFF Research Database (Denmark)

Lund, Line; Ross, Lone; Petersen, Morten Aagaard

2015-01-01

PURPOSE: In order to meet the caregiving challenges, informal caregivers often need a substantial level of interaction with health care professionals (HCPs). This study investigated to which extent the cancer caregivers' needs regarding the interaction with HCPs are met and the associations betwe...

Identification of new candidate drugs for lung cancer using chemical-chemical interactions, chemical-protein interactions and a K-means clustering algorithm.

Science.gov (United States)

Lu, Jing; Chen, Lei; Yin, Jun; Huang, Tao; Bi, Yi; Kong, Xiangyin; Zheng, Mingyue; Cai, Yu-Dong

2016-01-01

Lung cancer, characterized by uncontrolled cell growth in the lung tissue, is the leading cause of global cancer deaths. Until now, effective treatment of this disease is limited. Many synthetic compounds have emerged with the advancement of combinatorial chemistry. Identification of effective lung cancer candidate drug compounds among them is a great challenge. Thus, it is necessary to build effective computational methods that can assist us in selecting for potential lung cancer drug compounds. In this study, a computational method was proposed to tackle this problem. The chemical-chemical interactions and chemical-protein interactions were utilized to select candidate drug compounds that have close associations with approved lung cancer drugs and lung cancer-related genes. A permutation test and K-means clustering algorithm were employed to exclude candidate drugs with low possibilities to treat lung cancer. The final analysis suggests that the remaining drug compounds have potential anti-lung cancer activities and most of them have structural dissimilarity with approved drugs for lung cancer.

Direct observation of nanoparticle-cancer cell nucleus interactions.

Science.gov (United States)

Dam, Duncan Hieu M; Lee, Jung Heon; Sisco, Patrick N; Co, Dick T; Zhang, Ming; Wasielewski, Michael R; Odom, Teri W

2012-04-24

We report the direct visualization of interactions between drug-loaded nanoparticles and the cancer cell nucleus. Nanoconstructs composed of nucleolin-specific aptamers and gold nanostars were actively transported to the nucleus and induced major changes to the nuclear phenotype via nuclear envelope invaginations near the site of the construct. The number of local deformations could be increased by ultrafast, light-triggered release of the aptamers from the surface of the gold nanostars. Cancer cells with more nuclear envelope folding showed increased caspase 3 and 7 activity (apoptosis) as well as decreased cell viability. This newly revealed correlation between drug-induced changes in nuclear phenotype and increased therapeutic efficacy could provide new insight for nuclear-targeted cancer therapy.

Characterizing associations and SNP-environment interactions for GWAS-identified prostate cancer risk markers--results from BPC3.

Directory of Open Access Journals (Sweden)

Sara Lindstrom

2011-02-01

Full Text Available Genome-wide association studies (GWAS have identified multiple single nucleotide polymorphisms (SNPs associated with prostate cancer risk. However, whether these associations can be consistently replicated, vary with disease aggressiveness (tumor stage and grade and/or interact with non-genetic potential risk factors or other SNPs is unknown. We therefore genotyped 39 SNPs from regions identified by several prostate cancer GWAS in 10,501 prostate cancer cases and 10,831 controls from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3. We replicated 36 out of 39 SNPs (P-values ranging from 0.01 to 10⁻²⁸. Two SNPs located near KLK3 associated with PSA levels showed differential association with Gleason grade (rs2735839, P = 0.0001 and rs266849, P = 0.0004; case-only test, where the alleles associated with decreasing PSA levels were inversely associated with low-grade (as defined by Gleason grade < 8 tumors but positively associated with high-grade tumors. No other SNP showed differential associations according to disease stage or grade. We observed no effect modification by SNP for association with age at diagnosis, family history of prostate cancer, diabetes, BMI, height, smoking or alcohol intake. Moreover, we found no evidence of pair-wise SNP-SNP interactions. While these SNPs represent new independent risk factors for prostate cancer, we saw little evidence for effect modification by other SNPs or by the environmental factors examined.

Evidence of gene-environment interactions between common breast cancer susceptibility loci and established environmental risk factors.

Directory of Open Access Journals (Sweden)

Stefan Nickels

Full Text Available Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cancer. Data from 24 studies of the Breast Cancer Association Consortium were pooled. Using up to 34,793 invasive breast cancers and 41,099 controls, we examined whether the relative risks associated with 23 single nucleotide polymorphisms were modified by 10 established environmental risk factors (age at menarche, parity, breastfeeding, body mass index, height, oral contraceptive use, menopausal hormone therapy use, alcohol consumption, cigarette smoking, physical activity in women of European ancestry. We used logistic regression models stratified by study and adjusted for age and performed likelihood ratio tests to assess gene-environment interactions. All statistical tests were two-sided. We replicated previously reported potential interactions between LSP1-rs3817198 and parity (Pinteraction = 2.4 × 10(-6 and between CASP8-rs17468277 and alcohol consumption (Pinteraction = 3.1 × 10(-4. Overall, the per-allele odds ratio (95% confidence interval for LSP1-rs3817198 was 1.08 (1.01-1.16 in nulliparous women and ranged from 1.03 (0.96-1.10 in parous women with one birth to 1.26 (1.16-1.37 in women with at least four births. For CASP8-rs17468277, the per-allele OR was 0.91 (0.85-0.98 in those with an alcohol intake of <20 g/day and 1.45 (1.14-1.85 in those who drank ≥ 20 g/day. Additionally, interaction was found between 1p11.2-rs11249433 and ever being parous (Pinteraction = 5.3 × 10(-5, with a per-allele OR of 1.14 (1.11-1.17 in parous women and 0.98 (0.92-1.05 in nulliparous women. These data provide first strong evidence that the risk of breast cancer associated with some common genetic variants may vary with environmental risk factors.

Increased signaling entropy in cancer requires the scale-free property of protein interaction networks

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Teschendorff, Andrew E.; Banerji, Christopher R. S.; Severini, Simone; Kuehn, Reimer; Sollich, Peter

2015-01-01

One of the key characteristics of cancer cells is an increased phenotypic plasticity, driven by underlying genetic and epigenetic perturbations. However, at a systems-level it is unclear how these perturbations give rise to the observed increased plasticity. Elucidating such systems-level principles is key for an improved understanding of cancer. Recently, it has been shown that signaling entropy, an overall measure of signaling pathway promiscuity, and computable from integrating a sample's gene expression profile with a protein interaction network, correlates with phenotypic plasticity and is increased in cancer compared to normal tissue. Here we develop a computational framework for studying the effects of network perturbations on signaling entropy. We demonstrate that the increased signaling entropy of cancer is driven by two factors: (i) the scale-free (or near scale-free) topology of the interaction network, and (ii) a subtle positive correlation between differential gene expression and node connectivity. Indeed, we show that if protein interaction networks were random graphs, described by Poisson degree distributions, that cancer would generally not exhibit an increased signaling entropy. In summary, this work exposes a deep connection between cancer, signaling entropy and interaction network topology. PMID:25919796

Multiple Gene-Environment Interactions on the Angiogenesis Gene-Pathway Impact Rectal Cancer Risk and Survival

Directory of Open Access Journals (Sweden)

Noha Sharafeldin

2017-09-01

Full Text Available Characterization of gene-environment interactions (GEIs in cancer is limited. We aimed at identifying GEIs in rectal cancer focusing on a relevant biologic process involving the angiogenesis pathway and relevant environmental exposures: cigarette smoking, alcohol consumption, and animal protein intake. We analyzed data from 747 rectal cancer cases and 956 controls from the Diet, Activity and Lifestyle as a Risk Factor for Rectal Cancer study. We applied a 3-step analysis approach: first, we searched for interactions among single nucleotide polymorphisms on the pathway genes; second, we searched for interactions among the genes, both steps using Logic regression; third, we examined the GEIs significant at the 5% level using logistic regression for cancer risk and Cox proportional hazards models for survival. Permutation-based test was used for multiple testing adjustment. We identified 8 significant GEIs associated with risk among 6 genes adjusting for multiple testing: TNF (OR = 1.85, 95% CI: 1.10, 3.11, TLR4 (OR = 2.34, 95% CI: 1.38, 3.98, and EGR2 (OR = 2.23, 95% CI: 1.04, 4.78 with smoking; IGF1R (OR = 1.69, 95% CI: 1.04, 2.72, TLR4 (OR = 2.10, 95% CI: 1.22, 3.60 and EGR2 (OR = 2.12, 95% CI: 1.01, 4.46 with alcohol; and PDGFB (OR = 1.75, 95% CI: 1.04, 2.92 and MMP1 (OR = 2.44, 95% CI: 1.24, 4.81 with protein. Five GEIs were associated with survival at the 5% significance level but not after multiple testing adjustment: CXCR1 (HR = 2.06, 95% CI: 1.13, 3.75 with smoking; and KDR (HR = 4.36, 95% CI: 1.62, 11.73, TLR2 (HR = 9.06, 95% CI: 1.14, 72.11, EGR2 (HR = 2.45, 95% CI: 1.42, 4.22, and EGFR (HR = 6.33, 95% CI: 1.95, 20.54 with protein. GEIs between angiogenesis genes and smoking, alcohol, and animal protein impact rectal cancer risk. Our results support the importance of considering the biologic hypothesis to characterize GEIs associated with cancer outcomes.

Gene-environment interaction involving recently identified colorectal cancer susceptibility loci

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Kantor, Elizabeth D.; Hutter, Carolyn M.; Minnier, Jessica; Berndt, Sonja I.; Brenner, Hermann; Caan, Bette J.; Campbell, Peter T.; Carlson, Christopher S.; Casey, Graham; Chan, Andrew T.; Chang-Claude, Jenny; Chanock, Stephen J.; Cotterchio, Michelle; Du, Mengmeng; Duggan, David; Fuchs, Charles S.; Giovannucci, Edward L.; Gong, Jian; Harrison, Tabitha A.; Hayes, Richard B.; Henderson, Brian E.; Hoffmeister, Michael; Hopper, John L.; Jenkins, Mark A.; Jiao, Shuo; Kolonel, Laurence N.; Le Marchand, Loic; Lemire, Mathieu; Ma, Jing; Newcomb, Polly A.; Ochs-Balcom, Heather M.; Pflugeisen, Bethann M.; Potter, John D.; Rudolph, Anja; Schoen, Robert E.; Seminara, Daniela; Slattery, Martha L.; Stelling, Deanna L.; Thomas, Fridtjof; Thornquist, Mark; Ulrich, Cornelia M.; Warnick, Greg S.; Zanke, Brent W.; Peters, Ulrike; Hsu, Li; White, Emily

2014-01-01

BACKGROUND Genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) that are associated with risk of colorectal cancer (CRC). Prior research has evaluated the presence of gene-environment interaction involving the first 10 identified susceptibility loci, but little work has been conducted on interaction involving SNPs at recently identified susceptibility loci, including: rs10911251, rs6691170, rs6687758, rs11903757, rs10936599, rs647161, rs1321311, rs719725, rs1665650, rs3824999, rs7136702, rs11169552, rs59336, rs3217810, rs4925386, and rs2423279. METHODS Data on 9160 cases and 9280 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) and Colon Cancer Family Registry (CCFR) were used to evaluate the presence of interaction involving the above-listed SNPs and sex, body mass index (BMI), alcohol consumption, smoking, aspirin use, post-menopausal hormone (PMH) use, as well as intake of dietary calcium, dietary fiber, dietary folate, red meat, processed meat, fruit, and vegetables. Interaction was evaluated using a fixed-effects meta-analysis of an efficient Empirical Bayes estimator, and permutation was used to account for multiple comparisons. RESULTS None of the permutation-adjusted p-values reached statistical significance. CONCLUSIONS The associations between recently identified genetic susceptibility loci and CRC are not strongly modified by sex, BMI, alcohol, smoking, aspirin, PMH use, and various dietary factors. IMPACT Results suggest no evidence of strong gene-environment interactions involving the recently identified 16 susceptibility loci for CRC taken one at a time. PMID:24994789

The Interactions of microRNA and Epigenetic Modifications in Prostate Cancer

Directory of Open Access Journals (Sweden)

Prashant Kumar Singh

2013-08-01

Full Text Available Epigenetic modifiers play important roles in fine-tuning the cellular transcriptome. Any imbalance in these processes may lead to abnormal transcriptional activity and thus result in disease state. Distortions of the epigenome have been reported in cancer initiation and progression. DNA methylation and histone modifications are principle components of this epigenome, but more recently it has become clear that microRNAs (miRNAs are another major component of the epigenome. Interactions of these components are apparent in prostate cancer (CaP, which is the most common non-cutaneous cancer and second leading cause of death from cancer in the USA. Changes in DNA methylation, altered histone modifications and miRNA expression are functionally associated with CaP initiation and progression. Various aspects of the epigenome have also been investigated as biomarkers for different stages of CaP detection, though with limited success. This review aims to summarize key aspects of these mechanistic interactions within the epigenome and to highlight their translational potential as functional biomarkers. To this end, exploration of TCGA prostate cancer data revealed that expression of key CaP miRNAs inversely associate with DNA methylation. Given the importance and prevalence of these epigenetic events in CaP biology it is timely to understand further how different epigenetic components interact and influence each other.

TP53 genetic polymorphisms, interactions with lifestyle factors and lung cancer risk: a case control study in a Chinese population

OpenAIRE

Li, Yanli; Chang, Shen-Chih; Niu, Rungui; Liu, Li; Crabtree-Ide, Christina R; Zhao, Baoxing; Shi, Jianping; Han, Xiaoyou; Li, Jiawei; Su, Jia; Cai, Lin; Yu, Shunzhang; Zhang, Zuo-Feng; Mu, Lina

2013-01-01

Abstract Background A pathway-based genotyping analysis suggested rs2078486 was a novel TP53 SNP, but very few studies replicate this association. TP53 rs1042522 is the most commonly studied SNP, but very few studies examined its potential interaction with environmental factors in relation to lung cancer risk. This study aims to examine associations between two TP53 single-nucleotide polymorphisms (SNPs) (rs2078486, rs1042522), their potential interac...

Protein-protein interactions and cancer: targeting the central dogma.

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Garner, Amanda L; Janda, Kim D

2011-01-01

Between 40,000 and 200,000 protein-protein interactions have been predicted to exist within the human interactome. As these interactions are of a critical nature in many important cellular functions and their dysregulation is causal of disease, the modulation of these binding events has emerged as a leading, yet difficult therapeutic arena. In particular, the targeting of protein-protein interactions relevant to cancer is of fundamental importance as the tumor-promoting function of several aberrantly expressed proteins in the cancerous state is directly resultant of its ability to interact with a protein-binding partner. Of significance, these protein complexes play a crucial role in each of the steps of the central dogma of molecular biology, the fundamental processes of genetic transmission. With the many important discoveries being made regarding the mechanisms of these genetic process, the identification of new chemical probes are needed to better understand and validate the druggability of protein-protein interactions related to the central dogma. In this review, we provide an overview of current small molecule-based protein-protein interaction inhibitors for each stage of the central dogma: transcription, mRNA splicing and translation. Importantly, through our analysis we have uncovered a lack of necessary probes targeting mRNA splicing and translation, thus, opening up the possibility for expansion of these fields.

Systematic Search for Gene-Gene Interaction Effect on Prostate Cancer Risk

Science.gov (United States)

2013-07-01

Systematic Search for Gene-Gene Interaction 5a. CONTRACT NUMBER Effect on Prostate Cancer Risk 5b. GRANT NUMBER W81XWH-09-1-0488 5c. PROGRAM...Supported by this grant ) 1. Tao S, Wang Z, Feng J, Hsu FC, Jin G, Kin ST, Zhang Z, Gronberg H, Zheng, SL, Isaacs WB, XU J, Sun J. A Genome-Wide Search for...order interactions among estrogen- metabolism genes in sporadic breast cancer. Am J Hum Genet, 69, 138-47. 48. Marchini, J., Donnelly, P. and Cardon

Gene-Gene and Gene-Environment Interactions in the Etiology of Breast Cancer

National Research Council Canada - National Science Library

Adegoke, Olufemi

2003-01-01

The objective of this CDA is to evaluate the gene-gene and gene-environment interactions in the etiology of breast cancer in two ongoing case-control studies, the Shanghai Breast Cancer Study (SBCS...

P-MartCancer–Interactive Online Software to Enable Analysis of Shotgun Cancer Proteomic Datasets

Energy Technology Data Exchange (ETDEWEB)

Webb-Robertson, Bobbie-Jo M.; Bramer, Lisa M.; Jensen, Jeffrey L.; Kobold, Markus A.; Stratton, Kelly G.; White, Amanda M.; Rodland, Karin D.

2017-10-31

P-MartCancer is a new interactive web-based software environment that enables biomedical and biological scientists to perform in-depth analyses of global proteomics data without requiring direct interaction with the data or with statistical software. P-MartCancer offers a series of statistical modules associated with quality assessment, peptide and protein statistics, protein quantification and exploratory data analyses driven by the user via customized workflows and interactive visualization. Currently, P-MartCancer offers access to multiple cancer proteomic datasets generated through the Clinical Proteomics Tumor Analysis Consortium (CPTAC) at the peptide, gene and protein levels. P-MartCancer is deployed using Azure technologies (http://pmart.labworks.org/cptac.html), the web-service is alternatively available via Docker Hub (https://hub.docker.com/r/pnnl/pmart-web/) and many statistical functions can be utilized directly from an R package available on GitHub (https://github.com/pmartR).

Gene-environment interactions in cancer epidemiology: a National Cancer Institute Think Tank report.

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Hutter, Carolyn M; Mechanic, Leah E; Chatterjee, Nilanjan; Kraft, Peter; Gillanders, Elizabeth M

2013-11-01

Cancer risk is determined by a complex interplay of genetic and environmental factors. Genome-wide association studies (GWAS) have identified hundreds of common (minor allele frequency [MAF] > 0.05) and less common (0.01 Think Tank" on January 10-11, 2012. The objective of the Think Tank was to facilitate discussions on (1) the state of the science, (2) the goals of G × E interaction studies in cancer epidemiology, and (3) opportunities for developing novel study designs and analysis tools. This report summarizes the Think Tank discussion, with a focus on contemporary approaches to the analysis of G × E interactions. Selecting the appropriate methods requires first identifying the relevant scientific question and rationale, with an important distinction made between analyses aiming to characterize the joint effects of putative or established genetic and environmental factors and analyses aiming to discover novel risk factors or novel interaction effects. Other discussion items include measurement error, statistical power, significance, and replication. Additional designs, exposure assessments, and analytical approaches need to be considered as we move from the current small number of success stories to a fuller understanding of the interplay of genetic and environmental factors. © 2013 WILEY PERIODICALS, INC.

Curcumin as a clinically-promising anti-cancer agent: pharmacokinetics and drug interactions.

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Adiwidjaja, Jeffry; McLachlan, Andrew J; Boddy, Alan V

2017-09-01

Curcumin has been extensively studied for its anti-cancer properties. While a diverse array of in vitro and preclinical research support the prospect of curcumin use as an anti-cancer therapeutic, most human studies have failed to meet the intended clinical expectation. Poor systemic availability of orally-administered curcumin may account for this disparity. Areas covered: This descriptive review aims to concisely summarise available clinical studies investigating curcumin pharmacokinetics when administered in different formulations. A critical analysis of pharmacokinetic- and pharmacodynamic-based interactions of curcumin with concomitantly administered drugs is also provided. Expert opinion: The encouraging clinical results of curcumin administration are currently limited to people with colorectal cancer, given that sufficient curcumin concentrations persist in colonic mucosa. Higher parent curcumin systemic exposure, which can be achieved by several newer formulations, has important implications for optimal treatment of cancers other than those in gastrointestinal tract. Curcumin-drug pharmacokinetic interactions are also almost exclusively in the enterocytes, owing to extensive first pass metabolism and poor curcumin bioavailability. Greater scope of these interactions, i.e. modulation of the systemic elimination of co-administered drugs, may be expected from more-bioavailable curcumin formulations. Further studies are still warranted, especially with newer formulations to support the inclusion of curcumin in cancer therapy regimens.

Mathematical Modeling of E6-p53 interactions in Cervical Cancer

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Khattak, Faryal; Haseeb, Muhammad; Fazal, Sahar; Bhatti, A I; Ullah, Mukhtar

2017-04-01

Background: Cervical cancer is the third most common cancer in women throughout the world. The human papillomavirus (HPV) E6 viral protein plays an essential role in proteasomal degradation of the cancer suppressant protein p53. As a result, p53 negative regulation and apoptosis relevant activities are abrogated, facilitating development of cervical cancer. Methods: A mathematical model of E6-p53 interactions was developed using mathematical laws. In-silico simulations were carried out on CellDesigner and as a test case the small molecule drug RITA was considered for its ability to rescue the functions of tumor suppressor p53 by inhibiting E6 mediated proteasomal degradation. Results: Using a computational model we scrutinized how p53 responds to RITA, and chemical reactions of this small molecule drug were incorporated to perceive the full effects. The evolved strategy allowed the p53 response and rescue of its tumor suppressor function to be delineated, RITA being found to block p53 interactions with E6 associated proteins. Conclusion: We could develop a model of E6-p53 interactions with incorporation of actions of the small molecule drug RITA. Suppression of E6 associated proteins by RITA induces accumulation of tumor suppressant p53. Using CellDesigner to encode the model ensured that it can be easily modified and extended as more data become available. This strategy should play an effective role in the development of therapies against cancer. Creative Commons Attribution License

Genome-wide search for gene-gene interactions in colorectal cancer.

Directory of Open Access Journals (Sweden)

Shuo Jiao

Full Text Available Genome-wide association studies (GWAS have successfully identified a number of single-nucleotide polymorphisms (SNPs associated with colorectal cancer (CRC risk. However, these susceptibility loci known today explain only a small fraction of the genetic risk. Gene-gene interaction (GxG is considered to be one source of the missing heritability. To address this, we performed a genome-wide search for pair-wise GxG associated with CRC risk using 8,380 cases and 10,558 controls in the discovery phase and 2,527 cases and 2,658 controls in the replication phase. We developed a simple, but powerful method for testing interaction, which we term the Average Risk Due to Interaction (ARDI. With this method, we conducted a genome-wide search to identify SNPs showing evidence for GxG with previously identified CRC susceptibility loci from 14 independent regions. We also conducted a genome-wide search for GxG using the marginal association screening and examining interaction among SNPs that pass the screening threshold (p<10(-4. For the known locus rs10795668 (10p14, we found an interacting SNP rs367615 (5q21 with replication p = 0.01 and combined p = 4.19×10(-8. Among the top marginal SNPs after LD pruning (n = 163, we identified an interaction between rs1571218 (20p12.3 and rs10879357 (12q21.1 (nominal combined p = 2.51×10(-6; Bonferroni adjusted p = 0.03. Our study represents the first comprehensive search for GxG in CRC, and our results may provide new insight into the genetic etiology of CRC.

Excess Cancer Risk Assessment from Some Common X-Ray Examinations in Sabzevar County

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Mohammad Taghi Bahreyni Toossi

2011-09-01

Full Text Available Introduction: Nowadays ionizing radiation has a considerable contribution in medical diagnostic and treatment. Using ionizing radiation is increasing rapidly, so biological effects of ionizing radiation should be considered more. X-rays in the range of diagnostic radiology have hazardous effects and risks that are defined as random effects. These effects obey the LNT hypothesis that occur at low doses and include many types of cancer and genetic mutations. So it is very important to assess the risk of exposure in medical examinations. Cancer is one of these hazardous risks caused by low dose ionizing radiation that may occur during life after exposure. According to BEAR 7, low dose radiation is defined as radiation that produces doses near zero up to 100 mSv. Materials and Methods: This work was carried out in eight radiology centers in the Sabzevar county of Iran for 485 patients in eight typical x-ray examinations chosen for the study: chest PA, chest AP, lumbar spine AP, lumbar spine LAT, pelvis AP, abdomen AP, skull AP and Lat. In order to estimate the excess cancer risk, we need to obtain collective effective dose caused by radiation in the study population. Usually effective dose offers precise assessment of radiography examination injuries in adult patients. In this study, we used the PCXMC Monte Carlo based software to obtain effective dose and organ dose. This software calculates organ and effective dose following input of patient and radiographic conditions. Results: Average patient weight and height, entrance surface dose, parameters used for each type of examination, and DAP values were entered. Effective dose, collective effective dose, number of radiographs per year and the excess cancer risk arising from these radiographic examinations were then calculated.  Discussion and Conclusion: Excess risk of fatal cancer due to x-ray examinations in the study population was calculated by collective effective dose. This risk in the

Nature, Nurture, and Cancer Risks: Genetic and Nutritional Contributions to Cancer.

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Theodoratou, Evropi; Timofeeva, Maria; Li, Xue; Meng, Xiangrui; Ioannidis, John P A

2017-08-21

It is speculated that genetic variants are associated with differential responses to nutrients (known as gene-diet interactions) and that these variations may be linked to different cancer risks. In this review, we critically evaluate the evidence across 314 meta-analyses of observational studies and randomized controlled trials of dietary risk factors and the five most common cancers (breast, lung, prostate, colorectal, and stomach). We also critically evaluate the evidence across 13 meta-analyses of observational studies of gene-diet interactions for the same cancers. Convincing evidence for association was found only for the intake of alcohol and whole grains in relation to colorectal cancer risk. Three nutrient associations had highly suggestive evidence and another 15 associations had suggestive evidence. Among the examined gene-diet interactions, only one had moderately strong evidence.

Awareness of breast cancer risk factors and practice of breast self examination among high school students in Turkey

Directory of Open Access Journals (Sweden)

Çetinkaya Aynur

2008-10-01

Full Text Available Abstract Background Young breast cancer patients have a lower rate of survival than old breast cancer patients due to being diagnosed at advanced stages. Breast self-examination makes women more "breast aware", which in turn may lead to an earlier diagnosis of breast cancer. The purpose of this study was to investigate knowledge and practice of breast self-examination and to determine knowledge of risk factors for breast cancer among high school students. Methods This is a descriptive and cross-sectional study. It was conducted in a high school in Manisa, Turkey. The study sample included 718 female high school students. A socio-demographic characteristics data form, knowledge of breast self examination and risk factors for breast cancer form and breast self examination practice form were used to collect data. Results The female high school students had insufficient knowledge about breast self-examination and a low percentage of students reported that they had performed breast self examination monthly. The most common reason for not doing breast self- examination was "not knowing how to perform breast self-examination" (98.5%. Most of the students had little knowledge of the risk factors for breast cancer. The most widely known risk factor by the students was personal history of breast cancer (68.7%. There was a significant relation between breast self-examination practice and age, school grade, knowledge about breast cancer and knowledge about breast self- examination. Conclusion There is a need to increase knowledge of adolescent females about the risks of breast cancer and benefits of early detection. In fact, health care professionals can develop effective breast health care programs and help young women to acquire good health habits.

Inclusive Education: An Examination of School Relationships and Student Interactions

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Sanchez-Marti, Angelina; Ramirez-Iniguez, Alma A.

2012-01-01

The aim of this paper is to examine inclusive education in multicultural contexts from an interaction networks perspective. The paper is based on the idea that inclusive education can be better understood by studying how native and non-native students interact, and what kinds of networks they establish in school. To do so, we assume two premises:…

Prediction of Cancer Proteins by Integrating Protein Interaction, Domain Frequency, and Domain Interaction Data Using Machine Learning Algorithms

Directory of Open Access Journals (Sweden)

Chien-Hung Huang

2015-01-01

Full Text Available Many proteins are known to be associated with cancer diseases. It is quite often that their precise functional role in disease pathogenesis remains unclear. A strategy to gain a better understanding of the function of these proteins is to make use of a combination of different aspects of proteomics data types. In this study, we extended Aragues’s method by employing the protein-protein interaction (PPI data, domain-domain interaction (DDI data, weighted domain frequency score (DFS, and cancer linker degree (CLD data to predict cancer proteins. Performances were benchmarked based on three kinds of experiments as follows: (I using individual algorithm, (II combining algorithms, and (III combining the same classification types of algorithms. When compared with Aragues’s method, our proposed methods, that is, machine learning algorithm and voting with the majority, are significantly superior in all seven performance measures. We demonstrated the accuracy of the proposed method on two independent datasets. The best algorithm can achieve a hit ratio of 89.4% and 72.8% for lung cancer dataset and lung cancer microarray study, respectively. It is anticipated that the current research could help understand disease mechanisms and diagnosis.

Physical View on the Interactions Between Cancer Cells and the Endothelial Cell Lining During Cancer Cell Transmigration and Invasion

Science.gov (United States)

Mierke, Claudia T.

There exist many reviews on the biological and biochemical interactions of cancer cells and endothelial cells during the transmigration and tissue invasion of cancer cells. For the malignant progression of cancer, the ability to metastasize is a prerequisite. In particular, this means that certain cancer cells possess the property to migrate through the endothelial lining into blood or lymph vessels, and are possibly able to transmigrate through the endothelial lining into the connective tissue and follow up their invasion path in the targeted tissue. On the molecular and biochemical level the transmigration and invasion steps are well-defined, but these signal transduction pathways are not yet clear and less understood in regards to the biophysical aspects of these processes. To functionally characterize the malignant transformation of neoplasms and subsequently reveal the underlying pathway(s) and cellular properties, which help cancer cells to facilitate cancer progression, the biomechanical properties of cancer cells and their microenvironment come into focus in the physics-of-cancer driven view on the metastasis process of cancers. Hallmarks for cancer progression have been proposed, but they still lack the inclusion of specific biomechanical properties of cancer cells and interacting surrounding endothelial cells of blood or lymph vessels. As a cancer cell is embedded in a special environment, the mechanical properties of the extracellular matrix also cannot be neglected. Therefore, in this review it is proposed that a novel hallmark of cancer that is still elusive in classical tumor biological reviews should be included, dealing with the aspect of physics in cancer disease such as the natural selection of an aggressive (highly invasive) subtype of cancer cells displaying a certain adhesion or chemokine receptor on their cell surface. Today, the physical aspects can be analyzed by using state-of-the-art biophysical methods. Thus, this review will present

Protein-Protein Interaction Reagents | Office of Cancer Genomics

Science.gov (United States)

The CTD2 Center at Emory University has a library of genes used to study protein-protein interactions in mammalian cells. These genes are cloned in different mammalian expression vectors. A list of available cancer-associated genes can be accessed below. Emory_CTD^2_PPI_Reagents.xlsx Contact: Haian Fu

Effects of interactions between common genetic variants and alcohol consumption on colorectal cancer risk.

Science.gov (United States)

Song, Nan; Shin, Aesun; Oh, Jae Hwan; Kim, Jeongseon

2018-01-19

Genome-wide association studies (GWAS) have identified approximately 40 common genetic loci associated with colorectal cancer risk. To investigate possible gene-environment interactions (GEIs) between GWAS-identified single-nucleotide polymorphisms (SNPs) and alcohol consumption with respect to colorectal cancer, a hospital-based case-control study was conducted. Higher levels of alcohol consumption as calculated based on a standardized definition of a drink (1 drink=12.5g of ethanol) were associated with increased risk of colorectal cancer (OR=2.47, 95% CI=1.62-3.76 for heavy drinkers [>50g/day] compared to never drinkers; p trend colorectal cancer associated with the G allele of rs6687758 tended to increase among individuals in the heavier alcohol consumption strata. A statistically significant association between rs6687758 and colorectal cancer risk was observed among moderate alcohol drinkers who consumed between >12.5 and ≤50g of alcohol per day (OR=1.46, 95% CI=1.01-2.11). A total of 2,109 subjects (703 colorectal cancer patients and 1,406 healthy controls) were recruited from the Korean National Cancer Center. For genotyping, 30 GWAS-identified SNPs were selected. A logistic regression model was used to evaluate associations of SNPs and alcohol consumption with colorectal cancer risk. We also tested GEIs between SNPs and alcohol consumption using a logistic model with multiplicative interaction terms. Our results suggest that SNP rs6687758 at 1q41 may interact with alcohol consumption in the etiology of colorectal cancer.

Cancer mortality in women after repeated fluoroscopic examinations of the chest

International Nuclear Information System (INIS)

Boice, J.D.; Monson, R.R.; Rosenstein, M.

1981-01-01

Among 1,047 women fluoroscopically examined in average of 102 times during pneumothorax therapy for tuberculosis and followed up to 45 years (average . 27 yr), no increase in the total number of cancer deaths occurred when these women were compared to 717 women who received other treatments [relative risk (RR) . 0.8]. However, elevated risks of mortality from stomach cancer (RR . 2.3), rectal cancer (RR . 3.8), breast cancer (RR . 1.2), lung cancer (RR . 1.8), and leukemia (RR . 1.2) were observed, but none was statistically significant and all were based on very small numbers of deaths. These increases were balanced by decreases of genital cancer (RR . 0.2), pancreatic cancer (RR . 0.9), lymphoma (RR . 0.6), and all other cancers (RR . 0.1). Average cumulative absorbed doses were 110 rads for the lungs, 33 rads for the trunk, 13 rads for the active bone marrow, and 7 rads for the stomach. The following upper levels of excess risk could be excluded with 95% confidence: 3.5 deaths/10(6) woman-year (WY)-rad for lung cancer, 4.8 deaths/10(6) WY-rad for lymphoma, and 12 deaths/10(6) WY-rad for leukemia. These findings indicated that the carcinogenic effect of multiple low-dose X-ray exposures was not greater than that currently assumed

Genotype x diet interactions in mice predisposed to mammary cancer: II. Tumors and metastasis

DEFF Research Database (Denmark)

Gordon, Ryan R; Hunter, Kent W; Merrill, Michele La

2008-01-01

either a very high-fat or a matched-control-fat diet, and we measured growth, body composition, age at mammary tumor onset, tumor number and severity, and formation of pulmonary metastases. SNP genotyping across the genome facilitated analyses of QTL and QTL × diet interaction effects. Here we describe......High dietary fat intake and obesity may increase the risk of susceptibility to certain forms of cancer. To study the interactions of dietary fat, obesity, and metastatic mammary cancer, we created a population of F2 mice cosegregating obesity QTL and the MMTV-PyMT transgene. We fed the F2 mice...... effects of diet on mammary tumor and metastases phenotypes, mapping of tumor/metastasis modifier genes, and the interaction between dietary fat levels and effects of cancer modifiers. Results demonstrate that animals fed a high-fat diet are not only more likely to experience decreased mammary cancer...

Prognostic impact of Metadherin-SND1 interaction in colon cancer.

Science.gov (United States)

Wang, Nan; Du, Xilin; Zang, Li; Song, Nuan; Yang, Tao; Dong, Rui; Wu, Tao; He, Xianli; Lu, Jianguo

2012-12-01

The interaction between Metadherin (MTDH) and Staphylococcal nuclease homology domain containing 1 (SND1) is involved in tumorigenesis and tumor progression of several human malignancies. However, its roles in colon cancer are still unclear. To investigate the clinical value of MTDH and SND1 expression in colon cancer. Immunohistochemical staining was performed to detect the expression of MTDH and SND1 using human colon cancer and their corresponding non-cancerous colon tissues from 196 patients' biopsies. Positive expression of MTDH and SND1 were both increased in colon cancer tissues compared to paired non-cancerous colon tissues. There was a positive correlation between MTDH and SND1 expression in colon cancer tissues (r = 0.86, p colon cancer patients with positive expression of MTDH and SND1 were significantly shorter than those without their expression (both p = 0.01). Furthermore, multivariate Cox regression analysis suggested that positive expression of MTDH and SND1 was an independent poor prognostic predictor in colon cancer. Our data suggest that the increased expression of MTDH and/or SND1 is closely related to carcinogenesis, progression, and prognosis of colon cancer. The co-expression of MTDH/SND1 may be a novel distinctive marker to benefit us in prediction of the prognosis in colon cancer.

Examining patterns of association with defensive information processing about colorectal cancer screening.

Science.gov (United States)

McQueen, Amy; Swank, Paul R; Vernon, Sally W

2014-11-01

To reduce negative psychological affect from information or behavior that is inconsistent with one's positive self-concept, individuals use a variety of defensive strategies. It is unknown whether correlates differ across defenses. We examined correlates of four levels of defensive information processing about colorectal cancer screening. Cross-sectional surveys were completed by a convenience sample of 287 adults aged 50-75 years. Defenses measures were more consistently associated with individual differences (especially avoidant coping styles); however, situational variables involving health-care providers also were important. Future research should examine changes in defenses after risk communication and their relative impact on colorectal cancer screening. © The Author(s) 2013.

Interaction between radiation and other breast cancer risk factors

International Nuclear Information System (INIS)

Boice, J.D. Jr.; Stone, B.J.

1978-01-01

A follow-up study was conducted of 1764 women institutionalized for pulmonary tuberculosis between 1930 and 1954. Among 1047 women exposed to fluoroscopic chest X-rays during air collapse therapy of the lung, an excess of breast cancer was observed and previously reported (41 cases observed versus 23.3 expected). Among 717 comparison patients who received other treatments, no excess breast cancer risk was apparent (15 cases observed versus 14.1 expected). To determine whether breast cancer risk factors modify the carcinogenic effect of radiation, analyses were performed evaluating the interaction of radiation with indicators of breast cancer risk. The greatest radiation risk was found when radiation exposure occurred just before and during menarche. Similarly, exposures during first pregnancy appeared substantially more hazardous than exposures occurring before or after first pregnancy, suggesting that the condition of the breast at the time of pregnancy modifies the effect of radiation in such a way as to enhance the risk. Age at menopause did not appear to influence the risk of radiation exposure. Other than radiation, benign breast disease was the most significant breast cancer risk indicator. Benign breast disease was not seen to modify the effect of radiation exposure; however, excessive radiation exposure might have increased the incidence of benign breast disease, complicating the interaction analysis. Because of the uncertainty due to small-number sampling variation, these study results will require confirmation by a larger series. They do, however, suggest that stages when breast tissue undergoes high mitotic activity, e.g. menarche and pregnancy, are times of special vulnerability to the harmful effects of ionizing radiation

The Role of Red Meat and Flavonoid Consumption on Cancer Prevention: The Korean Cancer Screening Examination Cohort.

Science.gov (United States)

Kim, So Young; Wie, Gyung-Ah; Cho, Yeong-Ah; Kang, Hyun-Hee; Ryu, Kyoung-A; Yoo, Min-Kyong; Jun, Shinyoung; Kim, Seong-Ah; Ha, Kyungho; Kim, Jeongseon; Cho, Yoon Hee; Shin, Sangah; Joung, Hyojee

2017-08-25

Markedly increased red meat consumption is a cancer risk factor, while dietary flavonoids may help prevent the disease. The purpose of this study was to investigate the associations of red meat and flavonoid consumption with cancer risk, based on data from 8024 subjects, drawn from the 2004-2008 Cancer Screening Examination Cohort of the Korean National Cancer Center. Hazard ratios (HRs) were obtained by using a Cox proportional hazard model. During the mean follow-up period of 10.1 years, 443 cases were newly diagnosed with cancer. After adjusting for age, there was a significant correlation between cancer risk and the daily intake of ≥43 g of red meat per day (HR 1.31; 95% CI 1.01, 1.71; p = 0.045), and total flavonoid intake tended to decrease cancer risk (HR 0.70; 95% CI 0.49, 0.99; highest vs. lowest quartile; p -trend = 0.073) in men. Following multivariable adjustment, there were no statistically significant associations between flavonoid intake and overall cancer risk in individuals with high levels of red meat intake. Men with low daily red meat intake exhibited an inverse association between flavonoid consumption and cancer incidence (HR 0.41; 95% CI 0.21, 0.80; highest vs. lowest; p -trend = 0.017). Additional research is necessary to clarify the effects of flavonoid consumption on specific cancer incidence, relative to daily red meat intake.

Methodological issues in detecting gene-gene interactions in breast cancer susceptibility: a population-based study in Ontario

Directory of Open Access Journals (Sweden)

Onay Venus

2007-08-01

Full Text Available Abstract Background There is growing evidence that gene-gene interactions are ubiquitous in determining the susceptibility to common human diseases. The investigation of such gene-gene interactions presents new statistical challenges for studies with relatively small sample sizes as the number of potential interactions in the genome can be large. Breast cancer provides a useful paradigm to study genetically complex diseases because commonly occurring single nucleotide polymorphisms (SNPs may additively or synergistically disturb the system-wide communication of the cellular processes leading to cancer development. Methods In this study, we systematically studied SNP-SNP interactions among 19 SNPs from 18 key genes involved in major cancer pathways in a sample of 398 breast cancer cases and 372 controls from Ontario. We discuss the methodological issues associated with the detection of SNP-SNP interactions in this dataset by applying and comparing three commonly used methods: the logistic regression model, classification and regression trees (CART, and the multifactor dimensionality reduction (MDR method. Results Our analyses show evidence for several simple (two-way and complex (multi-way SNP-SNP interactions associated with breast cancer. For example, all three methods identified XPD-[Lys751Gln]*IL10-[G(-1082A] as the most significant two-way interaction. CART and MDR identified the same critical SNPs participating in complex interactions. Our results suggest that the use of multiple statistical approaches (or an integrated approach rather than a single methodology could be the best strategy to elucidate complex gene interactions that have generally very different patterns. Conclusion The strategy used here has the potential to identify complex biological relationships among breast cancer genes and processes. This will lead to the discovery of novel biological information, which will improve breast cancer risk management.

Short message service prompted mouth self-examination in oral cancer patients as an alternative to frequent hospital-based surveillance.

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Vaishampayan, Sagar; Malik, Akshat; Pawar, Prashant; Arya, Kavi; Chaturvedi, Pankaj

2017-01-01

Oral squamous cell carcinoma (OSCC) are amongst commonest cancer in the Indian sub-continent. After treatment, these patients require frequent followup to look for recurrences/second primary. Mouth Self Examination (MSE) has a great potential in all levels of prevention of oral cancer. However, the compliance to self-examination has been reported as poor. Mobile phone is a cheap and effective way to reach out to people. Short Message Service (SMS) is extremely popular can be a very effective motivational and interactive tool in health care setting. We aimed to identify in adequately treated OSCC patients, the influence of health provider initiated SMS on the compliance to the MSE and to establish the efficacy of MSE by comparing patients' MSE interpretation via replies to the SMS with that of the experts' opinion on clinical examination status during follow up. We conclude that MSE can be very useful in adequately treated OSCC patients for evaluating disease status. All treated OSCC patients must be adequately educated for MSE as an integral part of treatment & follow-up protocol by the health provider facility. Health provider generated SMS reminders do improve motivation and compliance towards MSE but don't seem to reduce dropouts in follow up for large and diverse population like that in India.

Protein-Protein Interactions (PPI) reagents: | Office of Cancer Genomics

Science.gov (United States)

The CTD2 Center at Emory University has a library of genes used to study protein-protein interactions in mammalian cells. These genes are cloned in different mammalian expression vectors. A list of available cancer-associated genes can be accessed below.

Effects of interactions between common genetic variants and alcohol consumption on colorectal cancer risk

Science.gov (United States)

Song, Nan; Shin, Aesun; Oh, Jae Hwan; Kim, Jeongseon

2018-01-01

Background Genome-wide association studies (GWAS) have identified approximately 40 common genetic loci associated with colorectal cancer risk. To investigate possible gene-environment interactions (GEIs) between GWAS-identified single-nucleotide polymorphisms (SNPs) and alcohol consumption with respect to colorectal cancer, a hospital-based case-control study was conducted. Results Higher levels of alcohol consumption as calculated based on a standardized definition of a drink (1 drink=12.5g of ethanol) were associated with increased risk of colorectal cancer (OR=2.47, 95% CI=1.62-3.76 for heavy drinkers [>50g/day] compared to never drinkers; ptrendcolorectal cancer associated with the G allele of rs6687758 tended to increase among individuals in the heavier alcohol consumption strata. A statistically significant association between rs6687758 and colorectal cancer risk was observed among moderate alcohol drinkers who consumed between >12.5 and ≤50g of alcohol per day (OR=1.46, 95% CI=1.01-2.11). Methods A total of 2,109 subjects (703 colorectal cancer patients and 1,406 healthy controls) were recruited from the Korean National Cancer Center. For genotyping, 30 GWAS-identified SNPs were selected. A logistic regression model was used to evaluate associations of SNPs and alcohol consumption with colorectal cancer risk. We also tested GEIs between SNPs and alcohol consumption using a logistic model with multiplicative interaction terms. Conclusions Our results suggest that SNP rs6687758 at 1q41 may interact with alcohol consumption in the etiology of colorectal cancer. PMID:29464080

Imaging of the interaction of cancer cells and the lymphatic system.

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Tran Cao, Hop S; McElroy, Michele; Kaushal, Sharmeela; Hoffman, Robert M; Bouvet, Michael

2011-09-10

A thorough understanding of the lymphatic system and its interaction with cancer cells is crucial to our ability to fight cancer metastasis. Efforts to study the lymphatic system had previously been limited by the inability to visualize the lymphatic system in vivo in real time. Fluorescence imaging can address these limitations and allow for visualization of lymphatic delivery and trafficking of cancer cells and potentially therapeutic agents as well. Here, we review recent articles in which antibody-fluorophore conjugates are used to label the lymphatic network and fluorescent proteins to label cancer cells in the evaluation of lymphatic delivery and imaging. Copyright © 2011 Elsevier B.V. All rights reserved.

Objective review of mediastinal lymph node examination in a lung cancer resection cohort.

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Osarogiagbon, Raymond U; Allen, Jeffrey W; Farooq, Aamer; Wu, James T

2012-02-01

Accurate staging of resected lung cancer requires mediastinal lymph node (MLN) examination. MLN dissection (MLND) and systematic sampling (SS) are acceptable procedures; random sampling (RS) and no sampling (NS) are not. Forty percent of US lung cancer resections have NS. We closely examined the pattern of MLN examination in a lung resection cohort. This is a retrospective review of all lung cancer resections in Memphis, TN, from 2004 to 2007. We compared operating surgeons' claims to the pathology report and an audit of the operation narrative by an independent surgeon. Forty-five percent of resections were reported by surgeons as MLND, 8% RS, and 48% NS. None met pathology criteria for MLND, 9% were SS, 50% were RS, and 42% were NS. The concordance rate between the operating surgeon and pathology report was 39%. The surgeon audit suggested 29% of resections had MLND, 26% RS, and 45% NS. Concordance between operating and auditing surgeons was 71%. Sublobar resection, T1 stage, and age were associated with NS. Most resections had suboptimal MLN examination. Concordance was poor between surgeon claims, objective review of pathology reports, and an independent surgeon audit. The higher concordance between operating and auditing surgeons may suggest incomplete pathology examination of MLN material. The terms used by operating surgeons to describe MLN retrieval were often inaccurate.

Contributions of cytology examination and methods in lung cancer diagnostic

International Nuclear Information System (INIS)

Jerse, M.; Tercelj, M.

2006-01-01

Background. Lung cancer (LC) is still the leading cause of cancer death according to published data worldwide and confirmed also by the data obtained from the central Cancer Registry of Slovenia. Early detection of LC has an important impact on the long-term survival rate of the patients. In spite of a great advance in imaging technology for a better visualization and early detection of the neoplasms and a variety of screening tests, only cytopathology examination finally define the neoplastic lesion. Methods. To evaluate the contribution of cytology examination in the diagnosis of LC we studied the cytology diagnoses, comparing them with histology reports in patients, who underwent the diagnostic procedure under suspicion of the LC during last 2 years. Results. Of a total 772 patients, in 241 patients cancer was microscopically confirmed. The most frequent diagnoses were adenocarcinoma (36.9%), squamous cell carcinoma (26.6%), and small cell carcinoma (SCLC) (12.9%). There were 22% of neoplasms classified as non-small cell carcinomas (NSCLC). From the clinician point of view considering the therapy it is very important to distinguish NSCLC from SCLC. And in our study the cytology-histology correlation between these two major types of carcinoma was almost 100%. Based only on cytology, 68 (28.2%) patients received microscopic diagnosis of malignoma, and the specimens for this group of patients were obtained mostly from transbronchial or transthoracic fine needle aspiration biopsies. Conclusions. Cytology is of great diagnostic value, a reliable and relatively non-invasive method for patients. Cytology specimens should be taken in cases where it is not possible to obtain samples for histology. (author)

Role of mammography in evaluating residual cancer of locally advanced breast carcinoma after neo-adjuvant chemotherapy : compared with clinical examination

International Nuclear Information System (INIS)

Choi, Byoung Wook; Kim, Eun Kyung; Oh, Ki Keun; Cho, Jae Min; Chung, Hyun Cheol; Lee, Byung Chan; Lee, Kyong Sik; Lee, Yong Hee

1997-01-01

To compare the usefulness of mammography and clinical examination in the evaluation of residual cancer of locally-advanced breast carcinoma treated with neoadjuvant chemotherapy. Among 67 patients with locally advanced breast carcinoma who were treated with neoadjuvant chemotherapy, 18, aged 35-67 (mean, 48) years, underwent mammography before and after this therapy. The 18 sets of mammographs were analyzed retrospectively and compared with the results of clinical examination based on histologic diagnosis. On histologic examinations, 16 of 18 patients (89%) were found to have residual cancer, but in one of these 16, mammography did not show this same result. On mammography, residual cancer was found in 16 patients, but in one of this group, histologic examination did not reveal the same finding. Clinically, a complete response was shown by four patients, and a partial response by 11 ; three showed no response. On histolgogic examination, three of the four patients with complete clinical response were found to have residual cancer. Post-treatment mammographic findings showed that 11 patients had measurable mass ; all of these had residual cancer (positive predictive value : 100%). However, five of seven patients in whom no measurable mass was evident also had residual cancer. Seven of 8 patients in whom microcalcifications were seen on mammography were found to have residual cancer (positive predictive value : 88%). The sensitivity of mammography in predicting residual cancer was greater than that of clinical examination (94% vs 81%), even when microscopic residual cancer was considered as a complete response (92% vs 77%). The specificity of mammography was the same as that of clinical examination(50% vs 50%, 20% vs 20%). In evaluating residual cancer of locally-advanced breast carcinoma after neoadjuvant chemotheragy, mammography is more accurate and informative than clincal examination. In predicting residual cancer, however, it is not accurate enough to replace

Testicular Cancer and Testicular Self-Examination; Knowledge, Attitudes and Practice in Final Year Medical Students in Nigeria

Science.gov (United States)

Ugwumba, Fred O; Ekwueme, Osa Eloka C; Okoh, Agharighom D

2016-11-01

The testicular cancer (TCa) incidence is increasing in many countries, with age-standardized incidence rates up to 7.8/100,000 men in the Western world, although reductions in mortality and increasingly high cure rates are being witnessed at the same time. In Africa, where rates are lower, presentation is often late and morbidity and mortality high. Given this scenario, awareness of testicular cancer and practice of testicular self-examination among future first response doctors is very important. This study was conducted to determine knowledge and attitude to testicular cancer, and practice of testicular self-examination (TSE) among final (6th) year medical students. In addition, the effect of an intervention in the form of a single PowerPoint® lecture, lasting 40 minutes with image content on testicular cancer and testicular self examination was assessed. Pre and post intervention administration of a self-administered structured pre tested questionnaire was performed on 151 medical students, 101 of whom returned answers (response rate of 66.8%). In the TC domain, there was a high level of awareness of testicular cancer, but poor knowledge of the age group most affected, with significant improvement post intervention (ptesticular self-examination pre-intervention was found considering the nature of the study group..Respondents had surprisingly weak/poor responses to the question “How important to men’s health is regular testicular self-examination?” Answers to the questions “Do you think it is worthwhile to examine your testis regularly?” and “Would you be interested in more information on testicular cancer and testicular self-examination?” were also suboptimal, but improved post intervention ptesticular cancer in the curricula of medical schools and other training institutions for health care personnel. Creative Commons Attribution License

Analysis of previous screening examinations for patients with breast cancer

International Nuclear Information System (INIS)

Lee, Eun Hye; Cha, Joo Hee; Han, Dae Hee; Choi, Young Ho; Hwang, Ki Tae; Ryu, Dae Sik; Kwak, Jin Ho; Moon, Woo Kyung

2007-01-01

We wanted to improve the quality of subsequent screening by reviewing the previous screening of breast cancer patients. Twenty-four breast cancer patients who underwent previous screening were enrolled. All 24 took mammograms and 15 patients also took sonograms. We reviewed the screening retrospectively according to the BI-RADS criteria and we categorized the results into false negative, true negative, true positive and occult cancers. We also categorized the causes of false negative cancers into misperception, misinterpretation and technical factors and then we analyzed the attributing factors. Review of the previous screening revealed 66.7% (16/24) false negative, 25.0% (6/24) true negative, and 8.3% (2/24) true positive cancers. False negative cancers were caused by the mammogram in 56.3% (9/16) and by the sonogram in 43.7% (7/16). For the false negative cases, all of misperception were related with mammograms and this was attributed to dense breast, a lesion located at the edge of glandular tissue or the image, and findings seen on one view only. Almost all misinterpretations were related with sonograms and attributed to loose application of the final assessment. To improve the quality of breast screening, it is essential to overcome the main causes of false negative examinations, including misperception and misinterpretation. We need systematic education and strict application of final assessment categories of BI-RADS. For effective communication among physicians, it is also necessary to properly educate them about BI-RADS

Water enema CT examination of rectum cancer by reduced amount of water

International Nuclear Information System (INIS)

Palko, A.; Gyulai, Cs.; Fedinecz, N.; Balogh, A.; Nagy, F.

2000-01-01

To define whether volume of water, administered during water enema CT (WE-CT) for local staging of rectal cancer, may be reduced without compromising the diagnostic value of the examination. Materials and Methods: 29 patients with rectum cancer underwent preoperative WE-CT. Contrast-enhanced CT (equilibrium phase) measurements were performed after i.v. injection of smooth muscle relaxant and rectal administration of 400 - 500 ml lukewarm tap water. Quality of the obtained scans was evaluated and the images were analyzed for depth of tumor invasion. Results of the CT examinations were compared to findings at surgery. Results: Despite reduced dose of water enema, 19/29 examinations were of excellent quality, 6/29 good, and 4/29 poor, but still diagnostic. We achieved sensitivity (90.1), specificity (70.1) and accuracy (86.2) in differentiating tumors confined to the bowel wall from those extending beyond it. Conclusion: Large volume of water enema administered during CT examination of the rectum may cause complaints and increases the risk of complications. Our results prove that using lower amount of water does not impair the quality of examination and accuracy of local staging of rectum carcinomas. (orig.) [de

The effect of the computer-assisted interactive video training interact-cancer on the communication skills of medical specialists in oncology.

NARCIS (Netherlands)

Hulsman, R.L.; Ros, W.J.G.; Winnubst, J.A.M.; Bensing, J.M.

1998-01-01

Introduction. INTERACT-CANCER is an interactive course for training communication skills of medical specialists in oncology. The course aims at teaching patient-centred behaviour. It includes four main topics in doctor-patient communication: basic skills, communicating bad news, informing patients,

A large-scale assessment of two-way SNP interactions in breast cancer susceptibility using 46,450 cases and 42,461 controls from the breast cancer association consortium

NARCIS (Netherlands)

Milne, Roger L.; Herranz, Jesús; Michailidou, Kyriaki; Dennis, Joe; Tyrer, Jonathan P.; Zamora, M. Pilar; Arias-Perez, José Ignacio; González-Neira, Anna; Pita, Guillermo; Alonso, M. Rosario; Wang, Qin; Bolla, Manjeet K.; Czene, Kamila; Eriksson, Mikael; Humphreys, Keith; Darabi, Hatef; Li, Jingmei; Anton-Culver, Hoda; Neuhausen, Susan L.; Ziogas, Argyrios; Clarke, Christina A.; Hopper, John L.; Dite, Gillian S.; Apicella, Carmel; Southey, Melissa C.; Chenevix-Trench, Georgia; Swerdlow, Anthony; Ashworth, Alan; Orr, Nicholas; Schoemaker, Minouk; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Mulligan, Anna Marie; Bojesen, Stig E.; Nordestgaard, Børge G.; Flyger, Henrik; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Molenaar, J.

2014-01-01

Part of the substantial unexplained familial aggregation of breast cancer may be due to interactions between common variants, but few studies have had adequate statistical power to detect interactions of realistic magnitude. We aimed to assess all two-way interactions in breast cancer susceptibility

Coping with early stage breast cancer: examining the influence of personality traits and interpersonal closeness

OpenAIRE

Saita, Emanuela; Acquati, Chiara; Kayser, Karen

2015-01-01

The study examines the influence of personality traits and close relationships on the coping style of women with breast cancer. A sample of seventy-two Italian patients receiving treatment for early stage breast cancer was recruited. Participants completed questionnaires measuring personality traits (Interpersonal Adaptation Questionnaire), interpersonal closeness (Inclusion of the Other in the Self Scale), and adjustment to cancer (Mini-Mental Adjustment to Cancer Scale). We hypothesized tha...

An interactive portal to empower cancer survivors: a qualitative study on user expectations

NARCIS (Netherlands)

Kuijpers, Wilma; Groen, Wim G.; Loos, Romy; Oldenburg, Hester S.A.; Wouters, Michel W.J.M.; Aaronson, Neil K.; van Harten, Willem H.

2015-01-01

Purpose Portals are increasingly used to improve patient empowerment, but are still uncommon in oncology. In this study, we explored cancer survivors’ and health professionals’ expectations of possible features of an interactive portal. Methods We conducted three focus groups with breast cancer

Interaction between tumor cell surface receptor RAGE and proteinase 3 mediates prostate cancer metastasis to bone

Science.gov (United States)

Kolonin, Mikhail G.; Sergeeva, Anna; Staquicini, Daniela I.; Smith, Tracey L.; Tarleton, Christy A.; Molldrem, Jeffrey J.; Sidman, Richard L.; Marchiò, Serena; Pasqualini, Renata; Arap, Wadih

2017-01-01

Human prostate cancer often metastasizes to bone, but the biological basis for such site-specific tropism remains largely unresolved. Recent work led us to hypothesize that this tropism may reflect pathogenic interactions between RAGE, a cell surface receptor expressed on malignant cells in advanced prostate cancer, and proteinase 3 (PR3), a serine protease present in inflammatory neutrophils and hematopoietic cells within the bone marrow microenvironment. In this study, we establish that RAGE-PR3 interaction mediates homing of prostate cancer cells to the bone marrow. PR3 bound to RAGE on the surface of prostate cancer cells in vitro, inducing tumor cell motility through a non-proteolytic signal transduction cascade involving activation and phosphorylation of ERK1/2 and JNK1. In preclinical models of experimental metastasis, ectopic expression of RAGE on human prostate cancer cells was sufficient to promote bone marrow homing within a short time frame. Our findings demonstrate how RAGE-PR3 interactions between human prostate cancer cells and the bone marrow microenvironment mediate bone metastasis during prostate cancer progression, with potential implications for prognosis and therapeutic intervention. PMID:28428279

A large-scale assessment of two-way SNP interactions in breast cancer susceptibility using 46,450 cases and 42,461 controls from the breast cancer association consortium.

Science.gov (United States)

Milne, Roger L; Herranz, Jesús; Michailidou, Kyriaki; Dennis, Joe; Tyrer, Jonathan P; Zamora, M Pilar; Arias-Perez, José Ignacio; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Wang, Qin; Bolla, Manjeet K; Czene, Kamila; Eriksson, Mikael; Humphreys, Keith; Darabi, Hatef; Li, Jingmei; Anton-Culver, Hoda; Neuhausen, Susan L; Ziogas, Argyrios; Clarke, Christina A; Hopper, John L; Dite, Gillian S; Apicella, Carmel; Southey, Melissa C; Chenevix-Trench, Georgia; Swerdlow, Anthony; Ashworth, Alan; Orr, Nicholas; Schoemaker, Minouk; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Bojesen, Stig E; Nordestgaard, Børge G; Flyger, Henrik; Nevanlinna, Heli; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Wang, Xianshu; Olson, Janet E; Vachon, Celine; Purrington, Kristen; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Dunning, Alison M; Shah, Mitul; Guénel, Pascal; Truong, Thérèse; Sanchez, Marie; Mulot, Claire; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Lindblom, Annika; Margolin, Sara; Hooning, Maartje J; Hollestelle, Antoinette; Collée, J Margriet; Jager, Agnes; Cox, Angela; Brock, Ian W; Reed, Malcolm W R; Devilee, Peter; Tollenaar, Robert A E M; Seynaeve, Caroline; Haiman, Christopher A; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Simard, Jacques; Dumont, Martine; Soucy, Penny; Dörk, Thilo; Bogdanova, Natalia V; Hamann, Ute; Försti, Asta; Rüdiger, Thomas; Ulmer, Hans-Ulrich; Fasching, Peter A; Häberle, Lothar; Ekici, Arif B; Beckmann, Matthias W; Fletcher, Olivia; Johnson, Nichola; dos Santos Silva, Isabel; Peto, Julian; Radice, Paolo; Peterlongo, Paolo; Peissel, Bernard; Mariani, Paolo; Giles, Graham G; Severi, Gianluca; Baglietto, Laura; Sawyer, Elinor; Tomlinson, Ian; Kerin, Michael; Miller, Nicola; Marme, Federik; Burwinkel, Barbara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Lambrechts, Diether; Yesilyurt, Betul T; Floris, Giuseppe; Leunen, Karin; Alnæs, Grethe Grenaker; Kristensen, Vessela; Børresen-Dale, Anne-Lise; García-Closas, Montserrat; Chanock, Stephen J; Lissowska, Jolanta; Figueroa, Jonine D; Schmidt, Marjanka K; Broeks, Annegien; Verhoef, Senno; Rutgers, Emiel J; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon-Dschun; Couch, Fergus J; Toland, Amanda E; Yannoukakos, Drakoulis; Pharoah, Paul D P; Hall, Per; Benítez, Javier; Malats, Núria; Easton, Douglas F

2014-04-01

Part of the substantial unexplained familial aggregation of breast cancer may be due to interactions between common variants, but few studies have had adequate statistical power to detect interactions of realistic magnitude. We aimed to assess all two-way interactions in breast cancer susceptibility between 70,917 single nucleotide polymorphisms (SNPs) selected primarily based on prior evidence of a marginal effect. Thirty-eight international studies contributed data for 46,450 breast cancer cases and 42,461 controls of European origin as part of a multi-consortium project (COGS). First, SNPs were preselected based on evidence (P 10(-10)). In summary, we observed little evidence of two-way SNP interactions in breast cancer susceptibility, despite the large number of SNPs with potential marginal effects considered and the very large sample size. This finding may have important implications for risk prediction, simplifying the modelling required. Further comprehensive, large-scale genome-wide interaction studies may identify novel interacting loci if the inherent logistic and computational challenges can be overcome.

Epistatic Interaction of CYP1A1 and COMT Polymorphisms in Cervical Cancer

Directory of Open Access Journals (Sweden)

Andreia Matos

2016-01-01

Full Text Available There is a clear association between the excessive and cumulative exposure to estrogens and the development of cancer in hormone-sensitive tissues, such as the cervix. We studied the association of CYP1A1 M1 (rs4646903 and COMT (rs4680 polymorphisms in 130 cervical cancer cases (c-cancer and 179 controls. The CYP1A1 TT genotype was associated with a lower risk for c-cancer (OR = 0.39, p=0.002. The allele C of CYP1A1 was a risk for c-cancer (OR = 2.29, p=0.002. Women with COMT LL genotype had a higher risk of developing c-cancer (OR = 4.83, p<0.001. For the interaction of the CYP1A1&COMT, we observed that TC&HL genotypes had a greater risk for c-cancer (OR = 6.07, p=0.006 and TT&HL genotypes had a protection effect (OR = 0.24, p<0.001. The CYP1A1 TT and COMT LL genotypes had higher estradiol levels in c-cancer (p<0.001 and p=0.037, resp.. C-cancer is associated with less production of 2-methoxy-estradiol resultant of functional polymorphisms of CYP1A1 and COMT, separately. CYP1A1 and COMT work in a metabolic sequence and their interaction could lead to an alternative pathway of estrogen metabolism with production of 16-OH-estrone that is more proliferative.

A large-scale assessment of two-way SNP interactions in breast cancer susceptibility using 46,450 cases and 42,461 controls from the breast cancer association consortium

DEFF Research Database (Denmark)

Milne, Roger L; Herranz, Jesús; Michailidou, Kyriaki

2014-01-01

susceptibility between 70,917 single nucleotide polymorphisms (SNPs) selected primarily based on prior evidence of a marginal effect. Thirty-eight international studies contributed data for 46,450 breast cancer cases and 42,461 controls of European origin as part of a multi-consortium project (COGS). First, SNPs......Part of the substantial unexplained familial aggregation of breast cancer may be due to interactions between common variants, but few studies have had adequate statistical power to detect interactions of realistic magnitude. We aimed to assess all two-way interactions in breast cancer...... 10(-10)). In summary, we observed little evidence of two-way SNP interactions in breast cancer susceptibility, despite the large number of SNPs with potential marginal effects considered and the very...

[Value of preoperative barium contrast examination for the diagnosis and operative planning in gastric cancer].

Science.gov (United States)

Wang, Chang-jian; Zhao, Guang-fa; Li, Qing-guo; Chen, Jing-gui; Zhu, Kai; Shi, Ying-qiang; Fu, Hong

2010-04-01

To investigate the value of preoperative barium contrast examination for the diagnosis and operative planning in gastric cancer. Clinical data of 229 gastric cancer patients were analyzed retrospectively. Lesions were divided into three parts: the cardiac, the body, and the antrum. The diagnostic accuracy of localization and the extent of tumor between gastroscopy alone and gastroscopy plus barium contrast were compared with the results of surgical findings. The diagnostic accuracy of localization and the extent of tumor for gastroscopy in the cardiac, the body and the antrum cancers were 100% and 78.4%, 94.6% and 86.5%, 98.1% and 84.6%, respectively, while for gastroscopy plus barium contrast were 100% and 84.8%, 100% and 91.9%, 99.0% and 90.4%, respectively. The diagnostic accuracy of both the localization and the extent of tumor were not significantly different between gastroscopy alone and gastroscopy plus barium contrast (P>0.05). Diagnostic accuracy of the length of esophagus infiltrated by cardiac cancer in gastroscopy was 60.6%, while in gastroscopy plus barium contrast was 90.9%, which was significantly different (Pbarium contrast was more accurate in predicting the possibility of thoracotomy in cardiac cancer infiltrating the lower esophagus. It is necessary to perform preoperative barium contrast examination in cardiac cancer patients, so as to identify whether the lower esophagus is infiltrated and to measure the length of lesion, which can provide evidences for making a decision of thoracotomy. For gastric body and antrum cancer, there is no indication for barium contrast examination if gastroscopy findings are satisfied.

Short message service prompted mouth self-examination in oral cancer patients as an alternative to frequent hospital-based surveillance

Directory of Open Access Journals (Sweden)

Sagar Vaishampayan

2017-01-01

Full Text Available Introduction: Oral squamous cell carcinoma (OSCC are amongst commonest cancer in the Indian sub-continent. After treatment, these patients require frequent followup to look for recurrences/second primary. Mouth Self Examination (MSE has a great potential in all levels of prevention of oral cancer. However, the compliance to self-examination has been reported as poor. Mobile phone is a cheap and effective way to reach out to people. Short Message Service (SMS is extremely popular can be a very effective motivational and interactive tool in health care setting. Methodology: We aimed to identify in adequately treated OSCC patients, the influence of health provider initiated SMS on the compliance to the MSE and to establish the efficacy of MSE by comparing patients' MSE interpretation via replies to the SMS with that of the experts' opinion on clinical examination status during follow up. Conclusion: We conclude that MSE can be very useful in adequately treated OSCC patients for evaluating disease status. All treated OSCC patients must be adequately educated for MSE as an integral part of treatment & follow-up protocol by the health provider facility. Health provider generated SMS reminders do improve motivation and compliance towards MSE but don't seem to reduce dropouts in follow up for large and diverse population like that in India.

Cancer Metastases to Bone: Concepts, Mechanisms, and Interactions with Bone Osteoblasts

Directory of Open Access Journals (Sweden)

Alison B. Shupp

2018-06-01

Full Text Available The skeleton is a unique structure capable of providing support for the body. Bone resorption and deposition are controlled in a tightly regulated balance between osteoblasts and osteoclasts with no net bone gain or loss. However, under conditions of disease, the balance between bone resorption and deposition is upset. Osteoblasts play an important role in bone homeostasis by depositing new bone osteoid into resorption pits. It is becoming increasingly evident that osteoblasts additionally play key roles in cancer cell dissemination to bone and subsequent metastasis. Our laboratory has evidence that when osteoblasts come into contact with disseminated breast cancer cells, the osteoblasts produce factors that initially reduce breast cancer cell proliferation, yet promote cancer cell survival in bone. Other laboratories have demonstrated that osteoblasts both directly and indirectly contribute to dormant cancer cell reactivation in bone. Moreover, we have demonstrated that osteoblasts undergo an inflammatory stress response in late stages of breast cancer, and produce inflammatory cytokines that are maintenance and survival factors for breast cancer cells and osteoclasts. Advances in understanding interactions between osteoblasts, osteoclasts, and bone metastatic cancer cells will aid in controlling and ultimately preventing cancer cell metastasis to bone.

Screening examinations for double cancer in patients with oral cancer. Usefulness of gastrointestinal endoscopy and positron emission tomography

International Nuclear Information System (INIS)

Takahashi, Hidenori; Umeda, Masahiro; Oguni, Akiko; Kataoka, Tomoko; Minamikawa, Tsutomu; Shibuya, Yasuyuki; Komori, Takahide; Shigeta, Takashi; Ri, Shinsho

2010-01-01

Many patients with oral cancer have double cancers, especially in the upper gastrointestinal tract. We studied synchronous double cancers in 138 patients with oral cancer who underwent gastrointestinal endscopy and 161 who underwent positron emission tomography (PET) preoperatively. Fifteen patients (10.9%) had cancer or precancerous lesions in the upper gastrointestinal tract on gastrointestinal endoscopy: 10 in the esophagus and 5 in the stomach. The histopathological diagnosis was severe epithelial dysplasia in 6 patients, carcinoma in situ in 4, and carcinoma in 5. These 15 lesions were asymptomatic and detected by gastrointestinal endscopy for the first time. Patients with severe epithelial dysplasia were observed, and those with carcinoma or carcinoma in situ underwent radical therapy. All of these gastrointestinal lesions were treated successfully, without any recurrence or metastasis. Double cancers were detected by PET in 3 patients (1.9%): lung and esophageal cancer, gastric cancer, and ovarian cancer in one patient each. These 3 cases also were detected by PET for the first time and were free of clinical symptoms. Radical therapy was performed in 2 patients. The other patient had advanced disease and received only palliative therapy. Although PET could not detect most cancers or precancerous lesions in the upper gastrointestinal tract that could be detected by gastrointestinal endscopy, it was useful for detecting malignant lesions in sites other than the upper gastrointestinal tract. Our results suggest that preoperative gastrointestinal endscopy and PET examinations can detect double cancer in the early stage and contribute to better outcomes in patients with oral cancer. (author)

Depressive symptoms predict head and neck cancer survival: Examining plausible behavioral and biological pathways.

Science.gov (United States)

Zimmaro, Lauren A; Sephton, Sandra E; Siwik, Chelsea J; Phillips, Kala M; Rebholz, Whitney N; Kraemer, Helena C; Giese-Davis, Janine; Wilson, Liz; Bumpous, Jeffrey M; Cash, Elizabeth D

2018-03-01

Head and neck cancers are associated with high rates of depression, which may increase the risk for poorer immediate and long-term outcomes. Here it was hypothesized that greater depressive symptoms would predict earlier mortality, and behavioral (treatment interruption) and biological (treatment response) mediators were examined. Patients (n = 134) reported depressive symptomatology at treatment planning. Clinical data were reviewed at the 2-year follow-up. Greater depressive symptoms were associated with significantly shorter survival (hazard ratio, 0.868; 95% confidence interval [CI], 0.819-0.921; P ratio, 0.865; 95% CI, 0.774-0.966; P = .010), and poorer treatment response (odds ratio, 0.879; 95% CI, 0.803-0.963; P = .005). The poorer treatment response partially explained the depression-survival relation. Other known prognostic indicators did not challenge these results. Depressive symptoms at the time of treatment planning predict overall 2-year mortality. Effects are partly influenced by the treatment response. Depression screening and intervention may be beneficial. Future studies should examine parallel biological pathways linking depression to cancer survival, including endocrine disruption and inflammation. Cancer 2018;124:1053-60. © 2018 American Cancer Society. © 2018 American Cancer Society.

Design and characterization of tunable hydrogels to examine microenvironmental regulation of breast cancer recurrence

Science.gov (United States)

Sawicki, Lisa A.

Late recurrence of breast cancer within distant metastatic tissue sites is often difficult to diagnose and treat, resulting in poor prognosis for patients. It is hypothesized that cells may go dormant by interactions with or lack of adhesion to the extracellular matrix (ECM) within these tissues, which differs from native breast tissue. The metastatic ECM is a complex microenvironment, containing a mixture of mechanical and chemical cues to which cells respond. To investigate how the ECM regulates cancer recurrence, two-dimensional (2D, plates) and three-dimensional (3D, naturally-derived scaffolds) in vitro culture models have been used. However, lack of complexity (2D), mechanical property control (2D, 3D), and chemical property control (3D) makes it challenging to identify key factors involved in regulating dormancy or activation in these systems. The development of synthetic polymer-based scaffolds in recent years provides an alternate route to investigating cellular response to the presentation of microenvironmental cues in 3D. Initially bioinert, these scaffolds may be modified with chemical ligands to permit cell-matrix interactions and their mechanical properties may be precisely tuned to mimic different tissue sites. The goal of this dissertation is to develop and characterize a novel synthetic material for cell culture applications and to examine how physical and chemical factors in this microenvironment regulate breast cancer activation. Specifically, we have developed a novel poly(ethylene glycol) (PEG)-based hydrogel scaffold for in vitro cell culture. PEG modified with thiols and peptides containing alloxycarbonyl-protected lysines (containing a reactive vinyl) react rapidly upon the application of light in the presence of a photoinitiator, lithium acylphosphinate ( minutes). Scaffold mechanical properties are tuned by varying macromer concentration to mimic soft metastatic site tissue ECMs (Young's modulus 600 - 6000 Pa). These properties remain

Do Interracial Interactions Matter? An Examination of Student-Faculty Contact and Intellectual Self-Concept

Science.gov (United States)

Cole, Darnell

2007-01-01

The purpose of this longitudinal, multi-institution study was to examine through multilevel analyses the influence of: (1) interracial interactions on student-faculty interactions; and (2) interracial interactions and student-faculty interactions on intellectual self-concept. Social participation and involvement theory, as they are constructed…

[Cancer treatment in Skane and in Sjaelland. Do differences concerning examination and treatment explain reduced survival among Danish cancer patients?

DEFF Research Database (Denmark)

Specht, Lena; Landberg, T.

2001-01-01

if differences in the diagnostic workup and treatment can explain some of this variation. MATERIAL AND METHODS: Aspects of the diagnostic workup and treatment of the above mentioned four cancer types are examined using data from cancer registry analyses and official reports. These data are seen in the context...... of counts of trained personnel and equipment in cancer diagnostics and treatment in the two countries. RESULTS: With regard to lung and breast cancer, the data seem to indicate that Danish patients are diagnosed later, and that Denmark lags behind in treatment capacity. With regard to rectal cancer......, the data seem to indicate that concentrating operations in fewer hospitals, and improvements in operation technique have been introduced earlier in Sweden than in Denmark. With regard to prostate cancer, however, the data seem to indicate that many more indolent cases that do not need treatment...

Interaction between common breast cancer susceptibility variants, genetic ancestry, and nongenetic risk factors in Hispanic women.

Science.gov (United States)

Fejerman, Laura; Stern, Mariana C; John, Esther M; Torres-Mejía, Gabriela; Hines, Lisa M; Wolff, Roger K; Baumgartner, Kathy B; Giuliano, Anna R; Ziv, Elad; Pérez-Stable, Eliseo J; Slattery, Martha L

2015-11-01

Most genetic variants associated with breast cancer risk have been discovered in women of European ancestry, and only a few genome-wide association studies (GWAS) have been conducted in minority groups. This research disparity persists in post-GWAS gene-environment interaction analyses. We tested the interaction between hormonal and lifestyle risk factors for breast cancer, and ten GWAS-identified SNPs among 2,107 Hispanic women with breast cancer and 2,587 unaffected controls, to gain insight into a previously reported gene by ancestry interaction in this population. We estimated genetic ancestry with a set of 104 ancestry-informative markers selected to discriminate between Indigenous American and European ancestry. We used logistic regression models to evaluate main effects and interactions. We found that the rs13387042-2q35(G/A) SNP was associated with breast cancer risk only among postmenopausal women who never used hormone therapy [per A allele OR: 0.94 (95% confidence intervals, 0.74-1.20), 1.20 (0.94-1.53), and 1.49 (1.28-1.75) for current, former, and never hormone therapy users, respectively, Pinteraction 0.002] and premenopausal women who breastfed >12 months [OR: 1.01 (0.72-1.42), 1.19 (0.98-1.45), and 1.69 (1.26-2.26) for never, 12 months breastfeeding, respectively, Pinteraction 0.014]. The correlation between genetic ancestry, hormone replacement therapy use, and breastfeeding behavior partially explained a previously reported interaction between a breast cancer risk variant and genetic ancestry in Hispanic women. These results highlight the importance of understanding the interplay between genetic ancestry, genetics, and nongenetic risk factors and their contribution to breast cancer risk. ©2015 American Association for Cancer Research.

Game theory in the death galaxy: interaction of cancer and stromal cells in tumour microenvironment.

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Wu, Amy; Liao, David; Tlsty, Thea D; Sturm, James C; Austin, Robert H

2014-08-06

Preventing relapse is the major challenge to effective therapy in cancer. Within the tumour, stromal (ST) cells play an important role in cancer progression and the emergence of drug resistance. During cancer treatment, the fitness of cancer cells can be enhanced by ST cells because their molecular signalling interaction delays the drug-induced apoptosis of cancer cells. On the other hand, competition among cancer and ST cells for space or resources should not be ignored. We explore the population dynamics of multiple myeloma (MM) versus bone marrow ST cells by using an experimental microecology that we call the death galaxy, with a stable drug gradient and connected microhabitats. Evolutionary game theory is a quantitative way to capture the frequency-dependent nature of interactive populations. Therefore, we use evolutionary game theory to model the populations in the death galaxy with the gradients of pay-offs and successfully predict the future densities of MM and ST cells. We discuss the possible clinical use of such analysis for predicting cancer progression.

Methylenetetrahydrofolate reductase polymorphisms and interaction with smoking and alcohol consumption in lung cancer risk: a case-control study in a Japanese population.

Science.gov (United States)

Kiyohara, Chikako; Horiuchi, Takahiko; Takayama, Koichi; Nakanishi, Yoichi

2011-10-25

Cigarette smoking is an established risk factor of lung cancer development while the current epidemiological evidence is suggestive of an increased lung cancer risk associated with alcohol consumption. Dietary folate, which is present in a wide range of fresh fruits and vegetables, may be a micronutrient that has a beneficial impact on lung carcinogenesis. Methylenetetrahydrofolate reductase (MTHFR) plays a crucial role in regulating folate metabolism, which affects both DNA synthesis/repair and methylation. We examined if smoking or alcohol consumption modify associations between MTHFR polymorphisms and lung cancer risk. We evaluated the role of the MTHFR C677T (rs1801133) and A1298C (rs1801131) polymorphisms in a case-control study comprised of 462 lung cancer cases and 379 controls in a Japanese population. Logistic regression was used to assess the adjusted odds ratios (OR) and 95% confidence intervals (95% CI). The TT genotype of the C677T polymorphism was significantly associated with an increased risk of lung cancer (OR = 2.27, 95% CI = 1.42 - 3.62, P fashion. The highest risks were seen for 677TT-carriers with a history of smoking or excessive drinking (OR = 6.16, 95% CI = 3.48 - 10.9 for smoking; OR = 3.09, 95% CI = 1.64 - 5.81 for drinking) compared with C-carriers without a history of smoking or excessive drinking, but no interactions were seen. The 1298CC genotype was only associated with increased risk among non-smokers (P < 0.05), and smoking was only associated with increased risks among 1298A-carriers (P < 0.01), but no significant interaction was seen. There was a synergistic interaction between the A1298C polymorphism and drinking (P < 0.05). The highest risk was seen for the CC-carriers with excessive drinking (OR = 7.24, 95% CI = 1.89 - 27.7) compared with the A-carriers without excessive drinking). The C677T polymorphism was significantly associated with lung cancer risk. Although the A1298C polymorphism was not associated with lung cancer risk

Prevalence of potential drug-drug interactions in cancer patients treated with oral anticancer drugs

NARCIS (Netherlands)

van Leeuwen, R. W. F.; Brundel, D. H. S.; Neef, C.; van Gelder, T.; Mathijssen, R. H. J.; Burger, D. M.; Jansman, F. G. A.

2013-01-01

Background: Potential drug-drug interactions (PDDIs) in patients with cancer are common, but have not previously been quantified for oral anticancer treatment. We assessed the prevalence and seriousness of potential PDDIs among ambulatory cancer patients on oral anticancer treatment. Methods: A

Prevalence of potential drug-drug interactions in cancer patients treated with oral anticancer drugs

NARCIS (Netherlands)

R.W.F. van Leeuwen (Roelof); D.H.S. Brundel (D. H S); C. Neef (Cees); T. van Gelder (Teun); A.H.J. Mathijssen (Ron); D.M. Burger (David); F.G.A. Jansman (Frank)

2013-01-01

textabstractBackground: Potential drug-drug interactions (PDDIs) in patients with cancer are common, but have not previously been quantified for oral anticancer treatment. We assessed the prevalence and seriousness of potential PDDIs among ambulatory cancer patients on oral anticancer treatment.

Drug-drug interactions in patients treated for cancer : a prospective study on clinical interventions

NARCIS (Netherlands)

van Leeuwen, R. W. F.; Jansman, F. G. A.; van den Bemt, P. M. L. A.; de Man, F.; Piran, F.; Vincenten, I.; Jager, A.; Rijneveld, A. W.; Brugma, J. D.; Mathijssen, R. H. J.; van Gelder, T.

Background: Drug-drug interactions (DDIs) are of major concern in oncology, since cancer patients typically take many concomitant medications. Retrospective studies have been conducted to determine the prevalence of DDIs. However, prospective studies on DDIs needing interventions in cancer patients

The interaction of bacterial magnetosomes and human liver cancer cells in vitro

Energy Technology Data Exchange (ETDEWEB)

Wang, Pingping, E-mail: wangpp@mail.iee.ac.cn [Beijing Key Laboratory of Bioelectromagnetism, Institute of Electrical Engineering, Chinese Academy of Sciences, Beijing 100190 (China); Chen, Chuanfang [Beijing Key Laboratory of Bioelectromagnetism, Institute of Electrical Engineering, Chinese Academy of Sciences, Beijing 100190 (China); Chen, Changyou [Beijing Key Laboratory of Bioelectromagnetism, Institute of Electrical Engineering, Chinese Academy of Sciences, Beijing 100190 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Li, Yue; Pan, Weidong; Song, Tao [Beijing Key Laboratory of Bioelectromagnetism, Institute of Electrical Engineering, Chinese Academy of Sciences, Beijing 100190 (China)

2017-04-01

As the biogenic magnetic nanomaterial, bacterial magnetic nanoparticles, namely magnetosomes, provide many advantages for potential biomedical applications. As such, interactions among magnetosomes and target cells should be elucidated to develop their bioapplications and evaluate their biocompatibilities. In this study, the interaction of magnetosomes and human liver cancer HepG2 cells was examined. Prussian blue staining revealed numerous stained particles in or on the cells. Intracellular iron concentrations, measured through inductively coupled plasma optical emission spectroscopy, increased with the increasing concentration of the magnetosomes. Transmission electron microscopy images showed that magnetosomes could be internalized in cells, mainly encapsulated in membrane vesicles, such as endosomes and lysosomes, and partly found as free particles in the cytosol. Some of the magnetosomes on cellular surfaces were encapsulated through cell membrane ruffling, which is the initiating process of endocytosis. Applying low temperature treatment and using specific endocytic inhibitors, we validated that macropinocytosis and clathrin-mediated endocytosis were involved in magnetosome uptake by HepG2 cells. Consequently, we revealed the interaction and intrinsic endocytic mechanisms of magnetosomes and HepG2 cells. This study provides a basis for the further research on bacterial magnetosome applications in liver diseases. - Highlights: • Bacterial magnetosomes interact with HepG2 cells in a dose-dependent manner. • Magnetosomes are wrapped by membrane ruffling on cell surface. • Internalized magnetosomes mainly localize in endosomes and lysosomes. • Macropinocytosis and CME are involved in the cellular uptake of magnetosomes.

Gene Environment Interactions and Predictors of Colorectal Cancer in Family-Based, Multi-Ethnic Groups.

Science.gov (United States)

Shiao, S Pamela K; Grayson, James; Yu, Chong Ho; Wasek, Brandi; Bottiglieri, Teodoro

2018-02-16

For the personalization of polygenic/omics-based health care, the purpose of this study was to examine the gene-environment interactions and predictors of colorectal cancer (CRC) by including five key genes in the one-carbon metabolism pathways. In this proof-of-concept study, we included a total of 54 families and 108 participants, 54 CRC cases and 54 matched family friends representing four major racial ethnic groups in southern California (White, Asian, Hispanics, and Black). We used three phases of data analytics, including exploratory, family-based analyses adjusting for the dependence within the family for sharing genetic heritage, the ensemble method, and generalized regression models for predictive modeling with a machine learning validation procedure to validate the results for enhanced prediction and reproducibility. The results revealed that despite the family members sharing genetic heritage, the CRC group had greater combined gene polymorphism rates than the family controls ( p relation to gene-environment interactions in the prevention of CRC.

Breast cancer screening activity in the Mie medical network, with special reference to the actual circumstances of detailed examination

International Nuclear Information System (INIS)

Nakai, Masahiro; Kawaguchi, Kanako; Kobayashi, Shigeki

2009-01-01

For clarifying both the current circumstances and problems of closed examination performed at facilities equipped for detailed examination in Mie Prefecture, we analyzed the results of closed examinations carried out on 1,001 responders who were selected by primary mammography screening done at 87 facilities in 2006. The overall breast cancer detection rate was 3.3%, with a range of 0-10.3%, for facilities that included family doctors, and 13 hospitals having performed the closed examination on 21 women or more. Although the location of a facility for closed examination and the background of examinees might be taken into consideration, it appeared that a higher cancer detection rate was obtained when more pathological examinations were carried out, and that the indications for pathological examination varied among physicians. At facilities where pathological examinations were frequently performed, mostly clinicians specializing in breast cancer performed either fine-needle aspiration biopsy or large-needle biopsy (a specific aspiration biopsy technique for calcified lesions), whereas at facilities with low rates of pathological examination, most surgeons not specializing in breast cancer performed open biopsy. These results suggest a need to draw up guidelines for detailed examination, including the standard of facilities for closed examination, clinicians who perform the examinations, and the examination methods. (author)

Association of Previous Clinical Breast Examination With Reduced Delays and Earlier-Stage Breast Cancer Diagnosis Among Women in Peru.

Science.gov (United States)

Romanoff, Anya; Constant, Tara Hayes; Johnson, Kay M; Guadiamos, Manuel Cedano; Vega, Ana María Burga; Zunt, Joseph; Anderson, Benjamin O

2017-11-01

Mammographic screening is impractical in most of the world where breast cancers are first identified based on clinical signs and symptoms. Clinical breast examination may improve early diagnosis directly by finding breast cancers at earlier stages or indirectly by heightening women's awareness of breast health concerns. To investigate factors that influence time to presentation and stage at diagnosis among patients with breast cancer to determine whether history of previous clinical breast examination is associated with earlier presentation and/or earlier cancer stage at diagnosis. In this cross-sectional analysis of individual patient interviews using a validated Breast Cancer Delay Questionnaire, 113 (71.1%) of 159 women with breast cancer treated at a federally funded tertiary care referral cancer center in Trujillo, Peru, from February 1 through May 31, 2015, were studied. Method of breast cancer detection and factors that influence time to and stage at diagnosis. Of 113 women with diagnosed cancer (mean [SD] age, 54 [10.8] years; age range, 32-82 years), 105 (92.9%) had self-detected disease. Of the 93 women for whom stage was documented, 45 (48.4%) were diagnosed with early-stage disease (American Joint Committee on Cancer [AJCC] stage 0, I, or II), and 48 (51.6%) were diagnosed with late-stage disease (AJCC stage III or IV). Mean (SD) total delay from symptom onset to initiation of treatment was 407 (665) days because of patient (mean [SD], 198 [449] days) and health care system (mean [SD], 241 [556] days) delay. Fifty-two women (46.0%) had a history of clinical breast examination, and 23 (20.4%) had undergone previous mammography. Women who underwent a previous clinical breast examination were more likely to have shorter delays from symptom development to presentation compared with women who had never undergone a previous clinical breast examination (odds ratio, 2.92; 95% CI, 1.30-6.60; P = .01). Women diagnosed with shorter patient delay were more

F-box protein interactions with the hallmark pathways in cancer.

Science.gov (United States)

Randle, Suzanne J; Laman, Heike

2016-02-01

F-box proteins (FBP) are the substrate specifying subunit of Skp1-Cul1-FBP (SCF)-type E3 ubiquitin ligases and are responsible for directing the ubiquitination of numerous proteins essential for cellular function. Due to their ability to regulate the expression and activity of oncogenes and tumour suppressor genes, FBPs themselves play important roles in cancer development and progression. In this review, we provide a comprehensive overview of FBPs and their targets in relation to their interaction with the hallmarks of cancer cell biology, including the regulation of proliferation, epigenetics, migration and invasion, metabolism, angiogenesis, cell death and DNA damage responses. Each cancer hallmark is revealed to have multiple FBPs which converge on common signalling hubs or response pathways. We also highlight the complex regulatory interplay between SCF-type ligases and other ubiquitin ligases. We suggest six highly interconnected FBPs affecting multiple cancer hallmarks, which may prove sensible candidates for therapeutic intervention. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Teachers' Beliefs Concerning Teaching about Testicular Cancer and Testicular Self-Examination.

Science.gov (United States)

Wohl, Royal E.; Kane, William M.

1997-01-01

This study compared secondary health teachers' beliefs concerning teaching about testicular cancer (TC) and self-examination (TSE) to actual instruction. TC and TSE education levels were low. Perceived barriers to teaching about TSE was the main predictor of TSE instruction. Teachers with previous preparation in TC and TSE provided the most…

Knowledge of Female Undergraduate Students on Breast Cancer and Breast Self-examination in Klang Valley, Malaysia.

Science.gov (United States)

Akhtari-Zavare, Mehrnoosh; Latiff, Latiffah A; Juni, Muhamad Hanafiah; Said, Salmiah Md; Ismail, Irmi Zarina

2015-01-01

In Malaysia, breast cancer is the first cancer among females regardness of race. The purpose of this study was to identify the knowledge and BSE practice among undergraduate female students at four public universities in Klang Valley, Malaysia. This cross-sectional study was conducted among 820 undergraduate female students using a self-administered questionnaire covering socio-demographic data, knowledge of breast cancer and BSE practice. The mean age of the respondents was 21.7±1.2 years. The majority of them were single (96.8%), Malay (91.9%) and 16.5% of respondents had a family history of breast cancer. This study showed low level of knowledge on breast cancer and breast self-examination among participants. Only 19.6% participants were performing BSE regularly. Knowledge of breast self-examination was significantly associated with BSE practice (p=0.00). Also, there were significant associations between performing BSE with age, marital status and being trained by a doctor for doing BSE (p<0.05). Our findings showed that the rate of BSE practice and knowledge of breast cancer is inadequate among young Malaysian females. A public health education program is essential to improve breast cancer prevention among this group.

Characterization of HPV and host genome interactions in primary head and neck cancers

Science.gov (United States)

Parfenov, Michael; Pedamallu, Chandra Sekhar; Gehlenborg, Nils; Freeman, Samuel S.; Danilova, Ludmila; Bristow, Christopher A.; Lee, Semin; Hadjipanayis, Angela G.; Ivanova, Elena V.; Wilkerson, Matthew D.; Protopopov, Alexei; Yang, Lixing; Seth, Sahil; Song, Xingzhi; Tang, Jiabin; Ren, Xiaojia; Zhang, Jianhua; Pantazi, Angeliki; Santoso, Netty; Xu, Andrew W.; Mahadeshwar, Harshad; Wheeler, David A.; Haddad, Robert I.; Jung, Joonil; Ojesina, Akinyemi I.; Issaeva, Natalia; Yarbrough, Wendell G.; Hayes, D. Neil; Grandis, Jennifer R.; El-Naggar, Adel K.; Meyerson, Matthew; Park, Peter J.; Chin, Lynda; Seidman, J. G.; Hammerman, Peter S.; Kucherlapati, Raju; Ally, Adrian; Balasundaram, Miruna; Birol, Inanc; Bowlby, Reanne; Butterfield, Yaron S.N.; Carlsen, Rebecca; Cheng, Dean; Chu, Andy; Dhalla, Noreen; Guin, Ranabir; Holt, Robert A.; Jones, Steven J.M.; Lee, Darlene; Li, Haiyan I.; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Robertson, A. Gordon; Schein, Jacqueline E.; Sipahimalani, Payal; Tam, Angela; Thiessen, Nina; Wong, Tina; Protopopov, Alexei; Santoso, Netty; Lee, Semin; Parfenov, Michael; Zhang, Jianhua; Mahadeshwar, Harshad S.; Tang, Jiabin; Ren, Xiaojia; Seth, Sahil; Haseley, Psalm; Zeng, Dong; Yang, Lixing; Xu, Andrew W.; Song, Xingzhi; Pantazi, Angeliki; Bristow, Christopher; Hadjipanayis, Angela; Seidman, Jonathan; Chin, Lynda; Park, Peter J.; Kucherlapati, Raju; Akbani, Rehan; Casasent, Tod; Liu, Wenbin; Lu, Yiling; Mills, Gordon; Motter, Thomas; Weinstein, John; Diao, Lixia; Wang, Jing; Fan, You Hong; Liu, Jinze; Wang, Kai; Auman, J. Todd; Balu, Saianand; Bodenheimer, Tom; Buda, Elizabeth; Hayes, D. Neil; Hoadley, Katherine A.; Hoyle, Alan P.; Jefferys, Stuart R.; Jones, Corbin D.; Kimes, Patrick K.; Marron, J.S.; Meng, Shaowu; Mieczkowski, Piotr A.; Mose, Lisle E.; Parker, Joel S.; Perou, Charles M.; Prins, Jan F.; Roach, Jeffrey; Shi, Yan; Simons, Janae V.; Singh, Darshan; Soloway, Mathew G.; Tan, Donghui; Veluvolu, Umadevi; Walter, Vonn; Waring, Scot; Wilkerson, Matthew D.; Wu, Junyuan; Zhao, Ni; Cherniack, Andrew D.; Hammerman, Peter S.; Tward, Aaron D.; Pedamallu, Chandra Sekhar; Saksena, Gordon; Jung, Joonil; Ojesina, Akinyemi I.; Carter, Scott L.; Zack, Travis I.; Schumacher, Steven E.; Beroukhim, Rameen; Freeman, Samuel S.; Meyerson, Matthew; Cho, Juok; Chin, Lynda; Getz, Gad; Noble, Michael S.; DiCara, Daniel; Zhang, Hailei; Heiman, David I.; Gehlenborg, Nils; Voet, Doug; Lin, Pei; Frazer, Scott; Stojanov, Petar; Liu, Yingchun; Zou, Lihua; Kim, Jaegil; Lawrence, Michael S.; Sougnez, Carrie; Lichtenstein, Lee; Cibulskis, Kristian; Lander, Eric; Gabriel, Stacey B.; Muzny, Donna; Doddapaneni, HarshaVardhan; Kovar, Christie; Reid, Jeff; Morton, Donna; Han, Yi; Hale, Walker; Chao, Hsu; Chang, Kyle; Drummond, Jennifer A.; Gibbs, Richard A.; Kakkar, Nipun; Wheeler, David; Xi, Liu; Ciriello, Giovanni; Ladanyi, Marc; Lee, William; Ramirez, Ricardo; Sander, Chris; Shen, Ronglai; Sinha, Rileen; Weinhold, Nils; Taylor, Barry S.; Aksoy, B. Arman; Dresdner, Gideon; Gao, Jianjiong; Gross, Benjamin; Jacobsen, Anders; Reva, Boris; Schultz, Nikolaus; Sumer, S. Onur; Sun, Yichao; Chan, Timothy; Morris, Luc; Stuart, Joshua; Benz, Stephen; Ng, Sam; Benz, Christopher; Yau, Christina; Baylin, Stephen B.; Cope, Leslie; Danilova, Ludmila; Herman, James G.; Bootwalla, Moiz; Maglinte, Dennis T.; Laird, Peter W.; Triche, Timothy; Weisenberger, Daniel J.; Van Den Berg, David J.; Agrawal, Nishant; Bishop, Justin; Boutros, Paul C.; Bruce, Jeff P; Byers, Lauren Averett; Califano, Joseph; Carey, Thomas E.; Chen, Zhong; Cheng, Hui; Chiosea, Simion I.; Cohen, Ezra; Diergaarde, Brenda; Egloff, Ann Marie; El-Naggar, Adel K.; Ferris, Robert L.; Frederick, Mitchell J.; Grandis, Jennifer R.; Guo, Yan; Haddad, Robert I.; Hammerman, Peter S.; Harris, Thomas; Hayes, D. Neil; Hui, Angela BY; Lee, J. Jack; Lippman, Scott M.; Liu, Fei-Fei; McHugh, Jonathan B.; Myers, Jeff; Ng, Patrick Kwok Shing; Perez-Ordonez, Bayardo; Pickering, Curtis R.; Prystowsky, Michael; Romkes, Marjorie; Saleh, Anthony D.; Sartor, Maureen A.; Seethala, Raja; Seiwert, Tanguy Y.; Si, Han; Tward, Aaron D.; Van Waes, Carter; Waggott, Daryl M.; Wiznerowicz, Maciej; Yarbrough, Wendell; Zhang, Jiexin; Zuo, Zhixiang; Burnett, Ken; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph; Penny, Robert; Shelton, Candance; Shelton, Troy; Sherman, Mark; Yena, Peggy; Black, Aaron D.; Bowen, Jay; Frick, Jessica; Gastier-Foster, Julie M.; Harper, Hollie A.; Lichtenberg, Tara M.; Ramirez, Nilsa C.; Wise, Lisa; Zmuda, Erik; Baboud, Julien; Jensen, Mark A.; Kahn, Ari B.; Pihl, Todd D.; Pot, David A.; Srinivasan, Deepak; Walton, Jessica S.; Wan, Yunhu; Burton, Robert; Davidsen, Tanja; Demchok, John A.; Eley, Greg; Ferguson, Martin L.; Shaw, Kenna R. Mills; Ozenberger, Bradley A.; Sheth, Margi; Sofia, Heidi J.; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean Claude; Saller, Charles; Tarvin, Katherine; Chen, Chu; Bollag, Roni; Weinberger, Paul; Golusiński, Wojciech; Golusiński, Paweł; Ibbs, Matthiew; Korski, Konstanty; Mackiewicz, Andrzej; Suchorska, Wiktoria; Szybiak, Bartosz; Wiznerowicz, Maciej; Burnett, Ken; Curley, Erin; Gardner, Johanna; Mallery, David; Penny, Robert; Shelton, Troy; Yena, Peggy; Beard, Christina; Mitchell, Colleen; Sandusky, George; Agrawal, Nishant; Ahn, Julie; Bishop, Justin; Califano, Joseph; Khan, Zubair; Bruce, Jeff P; Hui, Angela BY; Irish, Jonathan; Liu, Fei-Fei; Perez-Ordonez, Bayardo; Waldron, John; Boutros, Paul C.; Waggott, Daryl M.; Myers, Jeff; Lippman, Scott M.; Egea, Sophie; Gomez-Fernandez, Carmen; Herbert, Lynn; Bradford, Carol R.; Carey, Thomas E.; Chepeha, Douglas B.; Haddad, Andrea S.; Jones, Tamara R.; Komarck, Christine M.; Malakh, Mayya; McHugh, Jonathan B.; Moyer, Jeffrey S.; Nguyen, Ariane; Peterson, Lisa A.; Prince, Mark E.; Rozek, Laura S.; Sartor, Maureen A.; Taylor, Evan G.; Walline, Heather M.; Wolf, Gregory T.; Boice, Lori; Chera, Bhishamjit S.; Funkhouser, William K.; Gulley, Margaret L.; Hackman, Trevor G.; Hayes, D. Neil; Hayward, Michele C.; Huang, Mei; Rathmell, W. Kimryn; Salazar, Ashley H.; Shockley, William W.; Shores, Carol G.; Thorne, Leigh; Weissler, Mark C.; Wrenn, Sylvia; Zanation, Adam M.; Chiosea, Simion I.; Diergaarde, Brenda; Egloff, Ann Marie; Ferris, Robert L.; Romkes, Marjorie; Seethala, Raja; Brown, Brandee T.; Guo, Yan; Pham, Michelle; Yarbrough, Wendell G.

2014-01-01

Previous studies have established that a subset of head and neck tumors contains human papillomavirus (HPV) sequences and that HPV-driven head and neck cancers display distinct biological and clinical features. HPV is known to drive cancer by the actions of the E6 and E7 oncoproteins, but the molecular architecture of HPV infection and its interaction with the host genome in head and neck cancers have not been comprehensively described. We profiled a cohort of 279 head and neck cancers with next generation RNA and DNA sequencing and show that 35 (12.5%) tumors displayed evidence of high-risk HPV types 16, 33, or 35. Twenty-five cases had integration of the viral genome into one or more locations in the human genome with statistical enrichment for genic regions. Integrations had a marked impact on the human genome and were associated with alterations in DNA copy number, mRNA transcript abundance and splicing, and both inter- and intrachromosomal rearrangements. Many of these events involved genes with documented roles in cancer. Cancers with integrated vs. nonintegrated HPV displayed different patterns of DNA methylation and both human and viral gene expressions. Together, these data provide insight into the mechanisms by which HPV interacts with the human genome beyond expression of viral oncoproteins and suggest that specific integration events are an integral component of viral oncogenesis. PMID:25313082

Cancer and life-history traits: lessons from host-parasite interactions.

Science.gov (United States)

Ujvari, Beata; Beckmann, Christa; Biro, Peter A; Arnal, Audrey; Tasiemski, Aurelie; Massol, Francois; Salzet, Michel; Mery, Frederic; Boidin-Wichlacz, Celine; Misse, Dorothee; Renaud, Francois; Vittecoq, Marion; Tissot, Tazzio; Roche, Benjamin; Poulin, Robert; Thomas, Frederic

2016-04-01

Despite important differences between infectious diseases and cancers, tumour development (neoplasia) can nonetheless be closely compared to infectious disease because of the similarity of their effects on the body. On this basis, we predict that many of the life-history (LH) responses observed in the context of host-parasite interactions should also be relevant in the context of cancer. Parasites are thought to affect LH traits of their hosts because of strong selective pressures like direct and indirect mortality effects favouring, for example, early maturation and reproduction. Cancer can similarly also affect LH traits by imposing direct costs and/or indirectly by triggering plastic adjustments and evolutionary responses. Here, we discuss how and why a LH focus is a potentially productive but under-exploited research direction for cancer research, by focusing our attention on similarities between infectious disease and cancer with respect to their effects on LH traits and their evolution. We raise the possibility that LH adjustments can occur in response to cancer via maternal/paternal effects and that these changes can be heritable to (adaptively) modify the LH traits of their offspring. We conclude that LH adjustments can potentially influence the transgenerational persistence of inherited oncogenic mutations in populations.

Interactions between household air pollution and GWAS-identified lung cancer susceptibility markers in the Female Lung Cancer Consortium in Asia (FLCCA).

Science.gov (United States)

Hosgood, H Dean; Song, Minsun; Hsiung, Chao Agnes; Yin, Zhihua; Shu, Xiao-Ou; Wang, Zhaoming; Chatterjee, Nilanjan; Zheng, Wei; Caporaso, Neil; Burdette, Laurie; Yeager, Meredith; Berndt, Sonja I; Landi, Maria Teresa; Chen, Chien-Jen; Chang, Gee-Chen; Hsiao, Chin-Fu; Tsai, Ying-Huang; Chien, Li-Hsin; Chen, Kuan-Yu; Huang, Ming-Shyan; Su, Wu-Chou; Chen, Yuh-Min; Chen, Chung-Hsing; Yang, Tsung-Ying; Wang, Chih-Liang; Hung, Jen-Yu; Lin, Chien-Chung; Perng, Reury-Perng; Chen, Chih-Yi; Chen, Kun-Chieh; Li, Yao-Jen; Yu, Chong-Jen; Chen, Yi-Song; Chen, Ying-Hsiang; Tsai, Fang-Yu; Kim, Christopher; Seow, Wei Jie; Bassig, Bryan A; Wu, Wei; Guan, Peng; He, Qincheng; Gao, Yu-Tang; Cai, Qiuyin; Chow, Wong-Ho; Xiang, Yong-Bing; Lin, Dongxin; Wu, Chen; Wu, Yi-Long; Shin, Min-Ho; Hong, Yun-Chul; Matsuo, Keitaro; Chen, Kexin; Wong, Maria Pik; Lu, Dara; Jin, Li; Wang, Jiu-Cun; Seow, Adeline; Wu, Tangchun; Shen, Hongbing; Fraumeni, Joseph F; Yang, Pan-Chyr; Chang, I-Shou; Zhou, Baosen; Chanock, Stephen J; Rothman, Nathaniel; Lan, Qing

2015-03-01

We previously carried out a multi-stage genome-wide association study (GWAS) on lung cancer among never smokers in the Female Lung Cancer Consortium in Asia (FLCCA) (6,609 cases, 7,457 controls) that identified novel susceptibility loci at 10q25.2, 6q22.2, and 6p21.32, and confirmed two previously identified loci at 5p15.33 and 3q28. Household air pollution (HAP) attributed to solid fuel burning for heating and cooking, is the leading cause of the overall disease burden in Southeast Asia, and is known to contain lung carcinogens. To evaluate the gene-HAP interactions associated with lung cancer in loci independent of smoking, we analyzed data from studies participating in FLCCA with fuel use information available (n = 3; 1,731 cases; 1,349 controls). Coal use was associated with a 30% increased risk of lung cancer (OR 1.3, 95% CI 1.0-1.6). Among the five a priori SNPs identified by our GWAS, two showed a significant interaction with coal use (HLA Class II rs2395185, p = 0.02; TP63 rs4488809 (rs4600802), p = 0.04). The risk of lung cancer associated with coal exposure varied with the respective alleles for these two SNPs. Our observations provide evidence that genetic variation in HLA Class II and TP63 may modify the association between HAP and lung cancer risk. The roles played in the cell cycle and inflammation pathways by the proteins encoded by these two genes provide biological plausibility for these interactions; however, additional replication studies are needed in other non-smoking populations.

Identification of New Genetic Susceptibility Loci for Breast Cancer Through Consideration of Gene-Environment Interactions

Science.gov (United States)

Schoeps, Anja; Rudolph, Anja; Seibold, Petra; Dunning, Alison M.; Milne, Roger L.; Bojesen, Stig E.; Swerdlow, Anthony; Andrulis, Irene; Brenner, Hermann; Behrens, Sabine; Orr, Nicholas; Jones, Michael; Ashworth, Alan; Li, Jingmei; Cramp, Helen; Connley, Dan; Czene, Kamila; Darabi, Hatef; Chanock, Stephen J.; Lissowska, Jolanta; Figueroa, Jonine D.; Knight, Julia; Glendon, Gord; Mulligan, Anna M.; Dumont, Martine; Severi, Gianluca; Baglietto, Laura; Olson, Janet; Vachon, Celine; Purrington, Kristen; Moisse, Matthieu; Neven, Patrick; Wildiers, Hans; Spurdle, Amanda; Kosma, Veli-Matti; Kataja, Vesa; Hartikainen, Jaana M.; Hamann, Ute; Ko, Yon-Dschun; Dieffenbach, Aida K.; Arndt, Volker; Stegmaier, Christa; Malats, Núria; Arias Perez, JoséI.; Benítez, Javier; Flyger, Henrik; Nordestgaard, Børge G.; Truong, Théresè; Cordina-Duverger, Emilie; Menegaux, Florence; Silva, Isabel dos Santos; Fletcher, Olivia; Johnson, Nichola; Häberle, Lothar; Beckmann, Matthias W.; Ekici, Arif B.; Braaf, Linde; Atsma, Femke; van den Broek, Alexandra J.; Makalic, Enes; Schmidt, Daniel F.; Southey, Melissa C.; Cox, Angela; Simard, Jacques; Giles, Graham G.; Lambrechts, Diether; Mannermaa, Arto; Brauch, Hiltrud; Guénel, Pascal; Peto, Julian; Fasching, Peter A.; Hopper, John; Flesch-Janys, Dieter; Couch, Fergus; Chenevix-Trench, Georgia; Pharoah, Paul D. P.; Garcia-Closas, Montserrat; Schmidt, Marjanka K.; Hall, Per; Easton, Douglas F.; Chang-Claude, Jenny

2014-01-01

Genes that alter disease risk only in combination with certain environmental exposures may not be detected in genetic association analysis. By using methods accounting for gene-environment (G × E) interaction, we aimed to identify novel genetic loci associated with breast cancer risk. Up to 34,475 cases and 34,786 controls of European ancestry from up to 23 studies in the Breast Cancer Association Consortium were included. Overall, 71,527 single nucleotide polymorphisms (SNPs), enriched for association with breast cancer, were tested for interaction with 10 environmental risk factors using three recently proposed hybrid methods and a joint test of association and interaction. Analyses were adjusted for age, study, population stratification, and confounding factors as applicable. Three SNPs in two independent loci showed statistically significant association: SNPs rs10483028 and rs2242714 in perfect linkage disequilibrium on chromosome 21 and rs12197388 in ARID1B on chromosome 6. While rs12197388 was identified using the joint test with parity and with age at menarche (P-values = 3 × 10−07), the variants on chromosome 21 q22.12, which showed interaction with adult body mass index (BMI) in 8,891 postmenopausal women, were identified by all methods applied. SNP rs10483028 was associated with breast cancer in women with a BMI below 25 kg/m2 (OR = 1.26, 95% CI 1.15–1.38) but not in women with a BMI of 30 kg/m2 or higher (OR = 0.89, 95% CI 0.72–1.11, P for interaction = 3.2 × 10−05). Our findings confirm comparable power of the recent methods for detecting G × E interaction and the utility of using G × E interaction analyses to identify new susceptibility loci. PMID:24248812

How Cancer Patients Use and Benefit from an Interactive Cancer Communication System.

Science.gov (United States)

Han, Jeong Yeob; Hawkins, Robert; Baker, Timothy; Shah, Dhavan V; Pingree, Suzanne; Gustafson, David H

2017-10-01

Despite the mounting evidence of efficacy of eHealth interventions, their mechanisms of action remain unknown. The current study analyzed patient log data as each patient engaged in an eHealth system called the Comprehensive Health Enhancement Support System (CHESS) and reports on how patients engage with different combinations of eHealth services over time. Newly diagnosed breast cancer patients (N = 443) were given access for 6 months to one of four different configurations of CHESS: (1) Information, (2) Information and Support, (3) Information, Support, and Coaching (Full CHESS), and (4) Full CHESS and Mentor. Besides a baseline survey, three follow-up posttests were administered. Action log data on how patients engaged with the CHESS were also collected and merged with surveys to examine how patients benefit during the cancer experience. The findings suggest that usage patterns were not competitive, implying that cancer patients' access to more complex tools generates more use with their time spreading out over the diverse services. Despite overall decline in usage rates, it was less severe in Full CHESS and Mentor condition, suggesting that communication functions drive long-term engagement with the system. Notably, the strongest relation between use and cancer information competence appeared late in the follow-up period.

Genome-Wide Interaction Analyses between Genetic Variants and Alcohol Consumption and Smoking for Risk of Colorectal Cancer.

Directory of Open Access Journals (Sweden)

Jian Gong

2016-10-01

Full Text Available Genome-wide association studies (GWAS have identified many genetic susceptibility loci for colorectal cancer (CRC. However, variants in these loci explain only a small proportion of familial aggregation, and there are likely additional variants that are associated with CRC susceptibility. Genome-wide studies of gene-environment interactions may identify variants that are not detected in GWAS of marginal gene effects. To study this, we conducted a genome-wide analysis for interaction between genetic variants and alcohol consumption and cigarette smoking using data from the Colon Cancer Family Registry (CCFR and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO. Interactions were tested using logistic regression. We identified interaction between CRC risk and alcohol consumption and variants in the 9q22.32/HIATL1 (Pinteraction = 1.76×10-8; permuted p-value 3.51x10-8 region. Compared to non-/occasional drinking light to moderate alcohol consumption was associated with a lower risk of colorectal cancer among individuals with rs9409565 CT genotype (OR, 0.82 [95% CI, 0.74-0.91]; P = 2.1×10-4 and TT genotypes (OR,0.62 [95% CI, 0.51-0.75]; P = 1.3×10-6 but not associated among those with the CC genotype (p = 0.059. No genome-wide statistically significant interactions were observed for smoking. If replicated our suggestive finding of a genome-wide significant interaction between genetic variants and alcohol consumption might contribute to understanding colorectal cancer etiology and identifying subpopulations with differential susceptibility to the effect of alcohol on CRC risk.

Gene-gene and gene-environment interactions in prostate, breast and colorectal cancer

DEFF Research Database (Denmark)

Kopp, Tine Iskov

The incidence of cancer in the western world has increased steeply during the last 50 years. For three of the most prevalent cancer types in Denmark, prostate, breast and colorectal cancer (PC, BC and CRC, respectively), only a small fraction (1-15%) of the incidences are caused by highly penetrant...... in alcohol-related BC in postmenopausal women involving a specific polymorphism in PPARG (coding the peroxisome proliferatoractivated receptor (PPARγ)) and its interaction with the aromatase (encoded by CYP19A1) was investigated (Paper V-VI). The Danish prospective “Diet, Cancer and Health” cohort study...... as having strong influence on carcinogenesis. Therefore, very frequent, low effect polymorphisms may have a greater contribution on a population level in combination with environmental factors. Indeed, several dietary and life style factors are now well-established risk factors for different cancer types...

Predicted cancer risks induced by computed tomography examinations during childhood, by a quantitative risk assessment approach.

Science.gov (United States)

Journy, Neige; Ancelet, Sophie; Rehel, Jean-Luc; Mezzarobba, Myriam; Aubert, Bernard; Laurier, Dominique; Bernier, Marie-Odile

2014-03-01

The potential adverse effects associated with exposure to ionizing radiation from computed tomography (CT) in pediatrics must be characterized in relation to their expected clinical benefits. Additional epidemiological data are, however, still awaited for providing a lifelong overview of potential cancer risks. This paper gives predictions of potential lifetime risks of cancer incidence that would be induced by CT examinations during childhood in French routine practices in pediatrics. Organ doses were estimated from standard radiological protocols in 15 hospitals. Excess risks of leukemia, brain/central nervous system, breast and thyroid cancers were predicted from dose-response models estimated in the Japanese atomic bomb survivors' dataset and studies of medical exposures. Uncertainty in predictions was quantified using Monte Carlo simulations. This approach predicts that 100,000 skull/brain scans in 5-year-old children would result in eight (90 % uncertainty interval (UI) 1-55) brain/CNS cancers and four (90 % UI 1-14) cases of leukemia and that 100,000 chest scans would lead to 31 (90 % UI 9-101) thyroid cancers, 55 (90 % UI 20-158) breast cancers, and one (90 % UI risks without exposure). Compared to background risks, radiation-induced risks would be low for individuals throughout life, but relative risks would be highest in the first decades of life. Heterogeneity in the radiological protocols across the hospitals implies that 5-10 % of CT examinations would be related to risks 1.4-3.6 times higher than those for the median doses. Overall excess relative risks in exposed populations would be 1-10 % depending on the site of cancer and the duration of follow-up. The results emphasize the potential risks of cancer specifically from standard CT examinations in pediatrics and underline the necessity of optimization of radiological protocols.

Spatial evolutionary games of interaction among generic cancer cells

DEFF Research Database (Denmark)

Bach, L.A.; Sumpter, D.J.T.; Alsner, J.

2003-01-01

Evolutionary game models of cellular interactions have shown that heterogeneity in the cellular genotypic composition is maintained through evolution to stable coexistence of growth-promoting and non-promoting cell types. We generalise these mean-field models and relax the assumption of perfect m...... at a cellular level. This study thus points a new direction towards more plausible spatial tumour modelling and the understanding of cancerous growth....

MEDICI: Mining Essentiality Data to Identify Critical Interactions for Cancer Drug Target Discovery and Development | Office of Cancer Genomics

Science.gov (United States)

Protein-protein interactions (PPIs) mediate the transmission and regulation of oncogenic signals that are essential to cellular proliferation and survival, and thus represent potential targets for anti-cancer therapeutic discovery. Despite their significance, there is no method to experimentally disrupt and interrogate the essentiality of individual endogenous PPIs. The ability to computationally predict or infer PPI essentiality would help prioritize PPIs for drug discovery and help advance understanding of cancer biology.

The Use of Chemical-Chemical Interaction and Chemical Structure to Identify New Candidate Chemicals Related to Lung Cancer.

Directory of Open Access Journals (Sweden)

Lei Chen

Full Text Available Lung cancer causes over one million deaths every year worldwide. However, prevention and treatment methods for this serious disease are limited. The identification of new chemicals related to lung cancer may aid in disease prevention and the design of more effective treatments. This study employed a weighted network, constructed using chemical-chemical interaction information, to identify new chemicals related to two types of lung cancer: non-small lung cancer and small-cell lung cancer. Then, a randomization test as well as chemical-chemical interaction and chemical structure information were utilized to make further selections. A final analysis of these new chemicals in the context of the current literature indicates that several chemicals are strongly linked to lung cancer.

77 FR 24537 - Draft Standards and Best Practices for Interaction Between Medical Examiner/Coroner and Organ and...

Science.gov (United States)

2012-04-24

... Best Practices for Interaction Between Medical Examiner/Coroner and Organ and Tissue Procurement... Committee Standards and Best Practices for Interaction Between Medical Examiner/Coroner Offices and Organ... coroner/medical examiner office representatives, law enforcement agencies, organizations, and all other...

The results of screening examinations of breast cancer conducted from 2004 to 2005 in Sierpc poviat

International Nuclear Information System (INIS)

Nowicki, A.; Milecka, A.

2007-01-01

Background: Breast cancer is one of the most common malignant neoplasms among women in Poland. 11733 new cases were registered in 2003. Well organized screening examinations are the most effective method of fighting against breast cancer. Aim of study: The main objective of this work was a preliminary analysis of a prophylactic examination programme for breast cancer in Sierpc district performed by the Independent Unit of Public Health Care Centres in Sierpc during the period of 2004 to 2005. Material and methods: The research was performed based on retrospective analysis of files obtained from the Department of Radiology of the Independent Unit of Public Health Care Centres in Sierpc. Prophylactic examination for detection of breast cancer includes physical examination of the breast as well as mammography. Results: The research includes 1291 women, most of them at age 50-55 years (57.1 years on average). City residents represent the biggest group of women. Nearly half of women had their first menstruation at the age of 14 to 15 years. The last menstruation occurred at age between 46 and 50 years old most frequently. The average number of labours was 2.3 and 2.5 during the analyzed period. The first labour occurred most frequently in women at the age of 21 to 25 years old. Most of the women never took previously and still do not take hormonal medicines. 80% of women have done breast self examination but over half of them (60.8%) did it occasionally. Breast examination done by a gynaecologist was performed in 22% of women during the last year. Breast cancer did not occur among family members in most of the analyzed women. Breast pain was the most frequent complaint. Over half of women (64.6%) previously underwent mammography. The biggest group among them (31.1%) includes women who had mammography between 2003 and 2004. Adipose glandular breast texture was detected in near half of women (43.5%). The result of mammography was normal in most analyzed women (87.1%). A

Hepatitis B X-interacting protein promotes cisplatin resistance and regulates CD147 via Sp1 in ovarian cancer.

Science.gov (United States)

Zou, Wei; Ma, Xiangdong; Yang, Hong; Hua, Wei; Chen, Biliang; Cai, Guoqing

2017-03-01

Ovarian cancer is the highest mortality rate of all female reproductive malignancies. Drug resistance is a major cause of treatment failure in malignant tumors. Hepatitis B X-interacting protein acts as an oncoprotein, regulates cell proliferation, and migration in breast cancer. We aimed to investigate the effects and mechanisms of hepatitis B X-interacting protein on resistance to cisplatin in human ovarian cancer cell lines. The mRNA and protein levels of hepatitis B X-interacting protein were detected using RT-PCR and Western blotting in cisplatin-resistant and cisplatin-sensitive tissues, cisplatin-resistant cell lines A2780/CP and SKOV3/CP, and cisplatin-sensitive cell lines A2780 and SKOV3. Cell viability and apoptosis were measured to evaluate cellular sensitivity to cisplatin in A2780/CP cells. Luciferase reporter gene assay was used to determine the relationship between hepatitis B X-interacting protein and CD147. The in vivo function of hepatitis B X-interacting protein on tumor burden was assessed in cisplatin-resistant xenograft models. The results showed that hepatitis B X-interacting protein was highly expressed in ovarian cancer of cisplatin-resistant tissues and cells. Notably, knockdown of hepatitis B X-interacting protein significantly reduced cell viability in A2780/CP compared with cisplatin treatment alone. Hepatitis B X-interacting protein and cisplatin cooperated to induce apoptosis and increase the expression of c-caspase 3 as well as the Bax/Bcl-2 ratio. We confirmed that hepatitis B X-interacting protein up-regulated CD147 at the protein expression and transcriptional levels. Moreover, we found that hepatitis B X-interacting protein was able to activate the CD147 promoter through Sp1. In vivo, depletion of hepatitis B X-interacting protein decreased the tumor volume and weight induced by cisplatin. Taken together, these results indicate that hepatitis B X-interacting protein promotes cisplatin resistance and regulated CD147 via Sp1 in

Attitude Examination Related to Breast Cancer Among Women in Bács-Kiskun County, Hungary

Directory of Open Access Journals (Sweden)

Pakai Annamária

2016-08-01

Full Text Available Breast cancer is the most commonly diagnosed type of cancer and a leading cause of mortality among women both in developed and developing countries all over the world. Our research questions were the following: 1. What is the ratio of women participating in mammography screening? 2. What factors influence the attendance of the screening? A quantitative, cross-sectional, and descriptive study (2013 examined women aged 35-65 without a history of breast cancer from Kecskemét City and its region. Non-random, convenience sampling method was applied in the study. The self-edited and self-administered questionnaire included the following groups of questions: socio-demographic data, attitude examination related to screening, reasons for absence. Besides SPSS Statistics, 20.00 test, x2 test, t-test, and ANOVA were used (p<0.05. During the Principal Component Analysis, 23 variables of the motivational scale were grouped into six theoretical subgroups, and the Cronbach-alpha value was 0.758. The mean age of the participants was 49.96±8.91 years.71% of the interviewees never attended breast cancer screening. Regarding the sample, the mean age of women participating in the screening for the first time was 39.66±12.21 years. Women with college/university degree attained high scores on the knowledge test (p<0.05. A significant part of women went to the screening because they feel responsibility for their health status or due to the family history of breast cancer. Fear, shame, or inconveniencies during examination did not affect participation in screening. Prevention programs play a significant role in the improvement of the health status of the Hungarian population. Mortality and morbidity indicators can be reduced by regularly organized, preventive activities based on appropriate knowledge. Thus, the number of healthy years can be increased.

Interactional synchrony in chimpanzees: Examination through a finger-tapping experiment.

Science.gov (United States)

Yu, Lira; Tomonaga, Masaki

2015-05-11

Humans often unconsciously coordinate behaviour with that of others in daily life. This interpersonal coordination, including mimicry and interactional synchrony, has been suggested to play a fundamental role in social interaction. If this coordinative behavior is socially adaptive, it may be shared with other highly social animal species. The current study targeted chimpanzees, which phylogenetically are the closest living relatives of humans and live in complex social groups, and examined whether interactional synchrony would emerge in pairs of chimpanzees when auditory information about a partner's movement was provided. A finger-tapping task was introduced via touch panels to elicit repetitive and rhythmic movement from each chimpanzee. We found that one of four chimpanzees produced significant changes in both tapping tempo and timing of the tapping relative to its partner's tap when auditory sounds were provided. Although the current results may have limitations in generalizing to chimpanzees as a species, we suggest that a finger-tapping task is one potential method to investigate interactional synchrony in chimpanzees under a laboratory setup.

Hsp70-Bag3 interactions regulate cancer-related signaling networks.

Science.gov (United States)

Colvin, Teresa A; Gabai, Vladimir L; Gong, Jianlin; Calderwood, Stuart K; Li, Hu; Gummuluru, Suryaram; Matchuk, Olga N; Smirnova, Svetlana G; Orlova, Nina V; Zamulaeva, Irina A; Garcia-Marcos, Mikel; Li, Xiaokai; Young, Z T; Rauch, Jennifer N; Gestwicki, Jason E; Takayama, Shinichi; Sherman, Michael Y

2014-09-01

Bag3, a nucleotide exchange factor of the heat shock protein Hsp70, has been implicated in cell signaling. Here, we report that Bag3 interacts with the SH3 domain of Src, thereby mediating the effects of Hsp70 on Src signaling. Using several complementary approaches, we established that the Hsp70-Bag3 module is a broad-acting regulator of cancer cell signaling by modulating the activity of the transcription factors NF-κB, FoxM1, Hif1α, the translation regulator HuR, and the cell-cycle regulators p21 and survivin. We also identified a small-molecule inhibitor, YM-1, that disrupts the Hsp70-Bag3 interaction. YM-1 mirrored the effects of Hsp70 depletion on these signaling pathways, and in vivo administration of this drug was sufficient to suppress tumor growth in mice. Overall, our results defined Bag3 as a critical factor in Hsp70-modulated signaling and offered a preclinical proof-of-concept that the Hsp70-Bag3 complex may offer an appealing anticancer target. ©2014 American Association for Cancer Research.

Estimation of breast doses and breast cancer risk associated with repeated fluoroscopic chest examinations of women with tuberculosis

International Nuclear Information System (INIS)

Boice, J.D. Jr.; Rosenstein, M.; Trout, E.D.

1978-01-01

A methodology is presented to estimate cumulative breast dose and breast cancer risk for women exposed to repeated fluoroscopic chest examinations during air collapse therapy for pulmonary tuberculosis. Medical record abstraction, physician interview, patient contact, machine exposure measurements, and absorbed dose computations were combined to estimate average breast doses for 1047 Massachusetts women who were treated between 1930 and 1954. The methodology presented considers breast size and composition, patient orientation, x-ray field size and location, beam quality, type of examination, machine exposure rate, and exposure time during fluoroscopic examinations. The best estimate for the risk of radiation-induced cancer for the women living longer than 10 years after initial fluoroscopic exposure is 6.2 excess breast cancers per million woman-year-rad with 90% confidence limits of 2.8 and 10.7 cancers/10 6 WY-rad. When breast cancer risk is considered as a function of absorbed dose in the breast, instead of as a function of the number of fluoroscopic examinations, a linear dose--response relationship over the range of estimated doses is consistent with the data. However, because of the uncertainty due to small-sample variability and because of the wide range of assumptions regarding certain fluoroscopy conditions, other dose--response relationships are compatible with the data

Genome-Wide Interaction Analyses between Genetic Variants and Alcohol Consumption and Smoking for Risk of Colorectal Cancer

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Newcomb, Polly A.; Campbell, Peter T.; Baron, John A.; Berndt, Sonja I.; Bezieau, Stephane; Brenner, Hermann; Casey, Graham; Chan, Andrew T.; Chang-Claude, Jenny; Du, Mengmeng; Figueiredo, Jane C.; Gallinger, Steven; Giovannucci, Edward L.; Haile, Robert W.; Harrison, Tabitha A.; Hayes, Richard B.; Hoffmeister, Michael; Hopper, John L.; Hudson, Thomas J.; Jeon, Jihyoun; Jenkins, Mark A.; Küry, Sébastien; Le Marchand, Loic; Lin, Yi; Lindor, Noralane M.; Nishihara, Reiko; Ogino, Shuji; Potter, John D.; Rudolph, Anja; Schoen, Robert E.; Seminara, Daniela; Slattery, Martha L.; Thibodeau, Stephen N.; Thornquist, Mark; Toth, Reka; Wallace, Robert; White, Emily; Jiao, Shuo; Lemire, Mathieu; Hsu, Li; Peters, Ulrike

2016-01-01

Genome-wide association studies (GWAS) have identified many genetic susceptibility loci for colorectal cancer (CRC). However, variants in these loci explain only a small proportion of familial aggregation, and there are likely additional variants that are associated with CRC susceptibility. Genome-wide studies of gene-environment interactions may identify variants that are not detected in GWAS of marginal gene effects. To study this, we conducted a genome-wide analysis for interaction between genetic variants and alcohol consumption and cigarette smoking using data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Interactions were tested using logistic regression. We identified interaction between CRC risk and alcohol consumption and variants in the 9q22.32/HIATL1 (Pinteraction = 1.76×10−8; permuted p-value 3.51x10-8) region. Compared to non-/occasional drinking light to moderate alcohol consumption was associated with a lower risk of colorectal cancer among individuals with rs9409565 CT genotype (OR, 0.82 [95% CI, 0.74–0.91]; P = 2.1×10−4) and TT genotypes (OR,0.62 [95% CI, 0.51–0.75]; P = 1.3×10−6) but not associated among those with the CC genotype (p = 0.059). No genome-wide statistically significant interactions were observed for smoking. If replicated our suggestive finding of a genome-wide significant interaction between genetic variants and alcohol consumption might contribute to understanding colorectal cancer etiology and identifying subpopulations with differential susceptibility to the effect of alcohol on CRC risk. PMID:27723779

Research and development of the system for group examination of lung cancer by helical CT

International Nuclear Information System (INIS)

2003-03-01

For the ultimate purpose of heavy particle therapy of lung cancer at an early stage, the system in the title with low dose radiation has been investigated by cooperation of NIRS (as a leading part) and medical/industrial facilities all over the country. The project started essentially in 1984 and has been continuing at 2003. This book described Results hitherto and Materials for application to medical care at disaster (Hanshin-Awaji Earthquake Disaster in 1995) together with reference materials. Results contain all fields of nuclear medicine and of imaging involved in examination/diagnosis of lung cancer, achieved by NIRS, by Health management center and Faculty of Medicine, Chiba University and Japan Anti-Tuberculosis Association in Chiba, by the 3rd Department of Internal Medicine, Fac. Med., Chiba Univ., by Osaka Medical Center for Cancer and Cardiovascular Diseases, by Nippon Med. School, Arakawa-ku cancer protection center and Tokyo Metropolitan Univ. of Health Sciences, by Hitachi health management center, by Fukui Med. College, by Hitachi Medical Corp., by NTT research laboratories, and by Toyohashi Univ. of Technology. The Materials involve Process and summary of conducting the medical care activities, Improvement of the examination automobile, Supplementary equipments and measures for legal problems, System for the medical care activities, Record of the examination automobile activities, Problems in future, and Completion of the medical activities. Reference materials are related with the Materials above. (N.I.)

Breast cancer screening (breast self-examination, clinical breast exam, and mammography) in women referred to health centers in Tabriz, Iran.

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Khalili, Azizeh Farshbaf; Shahnazi, Mahnaz

2010-04-01

Breast cancer is the most common cancer and the most common cause of death in Iranian women aged 35-55 years. Breast cancer screening comprises breast self-examination (BSE), clinical breast examination (CBE) and mammography. The study aimed to examine the performance of screening methods among women referring to health centers of Tabriz, Iran. This was a descriptive-analytical research carried out on 400 women aged 20-50 years. The samples were chosen through random multistage sampling among health centers of Tabriz then active records of women. A questionnaire and observational checklist was used to elicit socio-demographic information and performance of women towards breast cancer screening methods. Descriptive and inferential statistics (chi-square and Fisher's exact test) were used to analyze the data. Only 18.8% of women did breast self-examination, 19.1% had clinical breast examination and 3.3% had mammogram. Statistical test showed a significant relationship between performing BSE and educational level, employment, income, number of children, breastfeeding history, breastfeeding quality and family history of breast cancer. There was a significant correlation between performing CBE and history of breast tumor and also, between performing the mammography and family history of breast cancer and history of breast tumor (P pre marriage counseling periods seems necessary.

"That Truly Meant a Lot to Me": A Qualitative Examination of Meaningful Faculty-Student Interactions

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Grantham, Ashley; Robinson, Emily Erin; Chapman, Diane

2015-01-01

The majority of research on faculty-student interaction has been primarily quantitative to date and has focused primarily on determining what kinds of interactions students have with faculty. This study furthers the literature on faculty-student interaction, taking a qualitative approach to examine what types of interactions with faculty students…

Physical and Functional Interactions between ELL2 and RB in the Suppression of Prostate Cancer Cell Proliferation, Migration, and Invasion

Directory of Open Access Journals (Sweden)

Xiaonan Qiu

2017-03-01

Full Text Available Elongation factor, RNA polymerase II, 2 (ELL2 is expressed and regulated by androgens in the prostate. ELL2 and ELL-associated factor 2 (EAF2 form a stable complex, and their orthologs in Caenorhabditis elegans appear to be functionally similar. In C. elegans, the EAF2 ortholog eaf-1 was reported to interact with the retinoblastoma (RB pathway to control development and fertility in worms. Because RB loss is frequent in prostate cancer, ELL2 interaction with RB might be important for prostate homeostasis. The present study explored physical and functional interaction of ELL2 with RB in prostate cancer. ELL2 expression in human prostate cancer specimens was detected using quantitative polymerase chain reaction coupled with laser capture microdissection. Co-immunoprecipitation coupled with deletion mutagenesis was used to determine ELL2 association with RB. Functional interaction between ELL2 and RB was tested using siRNA knockdown, BrdU incorporation, Transwell, and/or invasion assays in LNCaP, C4-2, and 22Rv1 prostate cancer cells. ELL2 expression was downregulated in high–Gleason score prostate cancer specimens. ELL2 could be bound and stabilized by RB, and this interaction was mediated through the N-terminus of ELL2 and the C-terminus of RB. Concurrent siRNA knockdown of ELL2 and RB enhanced cell proliferation, migration, and invasion as compared to knockdown of ELL2 or RB alone in prostate cancer cells. ELL2 and RB can interact physically and functionally to suppress prostate cancer progression.

The utility of Google Trends data to examine interest in cancer screening.

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Schootman, M; Toor, A; Cavazos-Rehg, P; Jeffe, D B; McQueen, A; Eberth, J; Davidson, N O

2015-06-08

We examined the utility of January 2004 to April 2014 Google Trends data from information searches for cancer screenings and preparations as a complement to population screening data, which are traditionally estimated through costly population-level surveys. State-level data across the USA. Persons who searched for terms related to cancer screening using Google, and persons who participated in the Behavioral Risk Factor Surveillance System (BRFSS). (1) State-level Google Trends data, providing relative search volume (RSV) data scaled to the highest search proportion per week (RSV100) for search terms over time since 2004 and across different geographical locations. (2) RSV of new screening tests, free/low-cost screening for breast and colorectal cancer, and new preparations for colonoscopy (Prepopik). (3) State-level breast, cervical, colorectal and prostate cancer screening rates. Correlations between Google Trends and BRFSS data ranged from 0.55 for ever having had a colonoscopy to 0.14 for having a Pap smear within the past 3 years. Free/low-cost mammography and colonoscopy showed higher RSV during their respective cancer awareness months. RSV for Miralax remained stable, while interest in Prepopik increased over time. RSV for lung cancer screening, virtual colonoscopy and three-dimensional mammography was low. Google Trends data provides enormous scientific possibilities, but are not a suitable substitute for, but may complement, traditional data collection and analysis about cancer screening and related interests. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Genome-wide identification of key modulators of gene-gene interaction networks in breast cancer.

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Chiu, Yu-Chiao; Wang, Li-Ju; Hsiao, Tzu-Hung; Chuang, Eric Y; Chen, Yidong

2017-10-03

With the advances in high-throughput gene profiling technologies, a large volume of gene interaction maps has been constructed. A higher-level layer of gene-gene interaction, namely modulate gene interaction, is composed of gene pairs of which interaction strengths are modulated by (i.e., dependent on) the expression level of a key modulator gene. Systematic investigations into the modulation by estrogen receptor (ER), the best-known modulator gene, have revealed the functional and prognostic significance in breast cancer. However, a genome-wide identification of key modulator genes that may further unveil the landscape of modulated gene interaction is still lacking. We proposed a systematic workflow to screen for key modulators based on genome-wide gene expression profiles. We designed four modularity parameters to measure the ability of a putative modulator to perturb gene interaction networks. Applying the method to a dataset of 286 breast tumors, we comprehensively characterized the modularity parameters and identified a total of 973 key modulator genes. The modularity of these modulators was verified in three independent breast cancer datasets. ESR1, the encoding gene of ER, appeared in the list, and abundant novel modulators were illuminated. For instance, a prognostic predictor of breast cancer, SFRP1, was found the second modulator. Functional annotation analysis of the 973 modulators revealed involvements in ER-related cellular processes as well as immune- and tumor-associated functions. Here we present, as far as we know, the first comprehensive analysis of key modulator genes on a genome-wide scale. The validity of filtering parameters as well as the conservativity of modulators among cohorts were corroborated. Our data bring new insights into the modulated layer of gene-gene interaction and provide candidates for further biological investigations.

Is there just one lesion? The need for whole body skin examination in patients presenting with non-melanocytic skin cancer.

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Terrill, Patricia Jane; Fairbanks, Sian; Bailey, Michael

2009-10-01

In patients presenting with non-melanoma skin cancer (NMSC) the frequency of concurrently presenting tumours is poorly documented. Whole body skin examination is recommended but in a recent survey of Australian General Practitioners and skin cancer clinics doctors it was infrequently performed. The aim of this study was to examine the incidence of concurrent skin cancer at initial presentation and therefore to examine the need for whole body skin examination for NMSC presentations. One hundred consecutive patients with a referral diagnosis indicative of NMSC were examined. Data was analysed as to the referring doctor's diagnosis, whole body skin examination findings and histology of excised lesions. Epidemiological data was obtained by patient questionnaire. One hundred patients, 41 males and 59 females, with a mean age of 70 years (range 39-91 years) underwent whole body skin examination. Sixty-seven per cent of patients were found to have additional lesions requiring treatment, 46% sin cancers (30 patients basal cell carcinomas, five squamous cell carcinomas, seven basal and squamous cell carcinomas, two lentigo maligna, two adenexal tumours) and 21% solar keratoses. Thirty-four of the additional lesions detected were in areas covered by clothing. Sixty-eight patients had a past history of skin cancer excision. In the Australian patient population, the need for whole body skin examination is essential to avoid missing concurrent lesions. Ongoing surveillance is also essential as these patients have a high risk of developing future NMSC.

Case-only gene-environment interaction between ALAD tagSNPs and occupational lead exposure in prostate cancer.

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Neslund-Dudas, Christine; Levin, Albert M; Rundle, Andrew; Beebe-Dimmer, Jennifer; Bock, Cathryn H; Nock, Nora L; Jankowski, Michelle; Datta, Indrani; Krajenta, Richard; Dou, Q Ping; Mitra, Bharati; Tang, Deliang; Rybicki, Benjamin A

2014-05-01

Black men have historically had higher blood lead levels than white men in the U.S. and have the highest incidence of prostate cancer in the world. Inorganic lead has been classified as a probable human carcinogen. Lead (Pb) inhibits delta-aminolevulinic acid dehydratase (ALAD), a gene recently implicated in other genitourinary cancers. The ALAD enzyme is involved in the second step of heme biosynthesis and is an endogenous inhibitor of the 26S proteasome, a master system for protein degradation and a current target of cancer therapy. Using a case-only study design, we assessed potential gene-environment (G × E) interactions between lifetime occupational Pb exposure and 11 tagSNPs within ALAD in black (N = 260) and white (N = 343) prostate cancer cases. Two ALAD tagSNPs in high linkage disequilibrium showed significant interaction with high Pb exposure among black cases (rs818684 interaction odds ratio or IOR = 2.73, 95% CI 1.43-5.22, P = 0.002; rs818689 IOR = 2.20, 95% CI 1.15-4.21, P = 0.017) and an additional tagSNP, rs2761016, showed G × E interaction with low Pb exposure (IOR = 2.08, 95% CI 1.13-3.84, P = 0.019). Further, the variant allele of rs818684 was associated with a higher Gleason grade in those with high Pb exposure among both blacks (OR 3.96, 95% CI 1.01-15.46, P = 0.048) and whites (OR 2.95, 95% CI 1.18-7.39, P = 0.020). Genetic variation in ALAD may modify associations between Pb and prostate cancer. Additional studies of ALAD, Pb, and prostate cancer are warranted and should include black men. Prostate 74:637-646, 2014. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

Assessing SNP-SNP interactions among DNA repair, modification and metabolism related pathway genes in breast cancer susceptibility.

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Yadav Sapkota

Full Text Available Genome-wide association studies (GWASs have identified low-penetrance common variants (i.e., single nucleotide polymorphisms, SNPs associated with breast cancer susceptibility. Although GWASs are primarily focused on single-locus effects, gene-gene interactions (i.e., epistasis are also assumed to contribute to the genetic risks for complex diseases including breast cancer. While it has been hypothesized that moderately ranked (P value based weak single-locus effects in GWASs could potentially harbor valuable information for evaluating epistasis, we lack systematic efforts to investigate SNPs showing consistent associations with weak statistical significance across independent discovery and replication stages. The objectives of this study were i to select SNPs showing single-locus effects with weak statistical significance for breast cancer in a GWAS and/or candidate-gene studies; ii to replicate these SNPs in an independent set of breast cancer cases and controls; and iii to explore their potential SNP-SNP interactions contributing to breast cancer susceptibility. A total of 17 SNPs related to DNA repair, modification and metabolism pathway genes were selected since these pathways offer a priori knowledge for potential epistatic interactions and an overall role in breast carcinogenesis. The study design included predominantly Caucasian women (2,795 cases and 4,505 controls from Alberta, Canada. We observed two two-way SNP-SNP interactions (APEX1-rs1130409 and RPAP1-rs2297381; MLH1-rs1799977 and MDM2-rs769412 in logistic regression that conferred elevated risks for breast cancer (P(interaction<7.3 × 10(-3. Logic regression identified an interaction involving four SNPs (MBD2-rs4041245, MLH1-rs1799977, MDM2-rs769412, BRCA2-rs1799943 (P(permutation = 2.4 × 10(-3. SNPs involved in SNP-SNP interactions also showed single-locus effects with weak statistical significance, while BRCA2-rs1799943 showed stronger statistical significance (P

Synergistic interaction of benign prostatic hyperplasia and prostatitis on prostate cancer risk

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Hung, S-C; Lai, S-W; Tsai, P-Y; Chen, P-C; Wu, H-C; Lin, W-H; Sung, F-C

2013-01-01

Background: The incidence of prostate cancer is much lower in Asian men than in Western men. This study investigated whether prostate cancer is associated with prostatitis, benign prostatic hyperplasia (BPH), and other medical conditions in the low-incidence population. Methods: From the claims data obtained from the universal National Health Insurance of Taiwan, we identified 1184 patients with prostate cancer diagnosed from 1997 to 2008. Controls comprised 4736 men randomly selected from a cancer-free population. Both groups were 50 years of age or above. Medical histories between the two groups were compared. Results: Multivariate logistic regression analysis showed that prostatitis and BPH had stronger association with prostate cancer than the other medical conditions tested. Compared with men without prostatitis and BPH, a higher odds ratio (OR) for prostate cancer was associated with BPH (26.2, 95% confidence interval (CI) 20.8–33.0) than with prostatitis (10.5, 95% CI=3.36–32.7). Men with both conditions had an OR of 49.2 (95% CI=34.7–69.9). Conclusion: Men with prostate cancer have strong association with prostatitis and/or BPH. Prostatitis interacts with BPH, resulting in higher estimated relative risk of prostate cancer in men suffering from both conditions. PMID:23612451

Physical examination of the female cancer patient with sexual concerns: What oncologists and patients should expect from consultation with a specialist.

Science.gov (United States)

Lindau, Stacy Tessler; Abramsohn, Emily M; Baron, Shirley R; Florendo, Judith; Haefner, Hope K; Jhingran, Anuja; Kennedy, Vanessa; Krane, Mukta K; Kushner, David M; McComb, Jennifer; Merritt, Diane F; Park, Julie E; Siston, Amy; Straub, Margaret; Streicher, Lauren

2016-05-01

Answer questions and earn CME/CNE Sexual concerns are prevalent in women with cancer or cancer history and are a factor in patient decision making about cancer treatment and risk-reduction options. Physical examination of the female cancer patient with sexual concerns, regardless of the type or site of her cancer, is an essential and early component of a comprehensive evaluation and effective treatment plan. Specialized practices are emerging that focus specifically on evaluation and treatment of women with cancer and sexual function problems. As part of a specialized evaluation, oncologists and their patients should expect a thorough physical examination to identify or rule out physical causes of sexual problems or dysfunction. This review provides oncology professionals with a description of the physical examination of the female cancer patient with sexual function concerns. This description aims to inform anticipatory guidance for the patient and to assist in interpreting specialists' findings and recommendations. In centers or regions where specialized care is not yet available, this review can also be used by oncology practices to educate and support health care providers interested in expanding their practices to treat women with cancer and sexual function concerns. CA Cancer J Clin 2016;66:241-263. © 2016 American Cancer Society. © 2016 American Cancer Society, Inc.

BAG3 sensitizes cancer cells exposed to DNA damaging agents via direct interaction with GRP78.

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Kong, De-Hui; Zhang, Qiang; Meng, Xin; Zong, Zhi-Hong; Li, Chao; Liu, Bao-Qin; Guan, Yifu; Wang, Hua-Qin

2013-12-01

Bcl-2 associated athanogene 3 (BAG3) has a modular structure that contains a BAG domain, a WW domain, a proline-rich (PxxP) domain to mediate potential interactions with chaperons and other proteins that participate in more than one signal transduction. In search for novel interacting partners, the current study identified that 78kDa glucose-regulated protein (GRP78) was a novel partner interacting with BAG3. Interaction between GRP78 and BAG3 was confirmed by coimmunoprecipitation and glutathione S-transferase (GST) pulldown. We also identified that the ATPase domain of GRP78 and BAG domain of BAG3 mediated their interaction. Counterintuitive for a prosurvival protein, BAG3 was found to promote the cytotoxicity of breast cancer MCF7, thyroid cancer FRO and glioma U87 cells subjected to genotoxic stress. In addition, the current study demonstrated that BAG3 interfered with the formation of the antiapoptotic GRP78-procaspase-7 complex, which resulted in an increased genotoxic stress-induced cytotoxicity in cancer cells. Furthermore, overexpression of GRP78 significantly blocked the enhancing effects of BAG3 on activation of caspase-7 and induction of apoptosis by genotoxic stress. Overall, these results suggested that through direct interaction BAG3 could prevent the antiapoptotic effect of GRP78 upon genotoxic stress. © 2013.

Interaction of vinyl chloride monomer exposure and hepatitis B viral infection on liver cancer.

Science.gov (United States)

Wong, Ruey-Hong; Chen, Pau-Chung; Wang, Jung-Der; Du, Chung-Li; Cheng, Tsun-Jen

2003-04-01

Vinyl-chloride monomer (VCM), a human carcinogen, has caused angiosarcoma of the liver. Recent studies have shown that VCM exposure is associated with hepatocellular cancer. In Taiwanese studies, the majority of VCM-exposed workers with liver cancer had history of hepatitis B virus (HBV) infection. To determine the role of HBV on the development of liver cancer in the VCM-exposed workers, we conducted a case-control study from a previously established polyvinyl chloride (PVC) cohort consisting of 4096 male workers from six PVC polymerization plants. A total of 18 patients with liver cancer, and 68 control subjects matched for age and specific plant of employment were selected. Detailed history of the participants that included alcohol consumption status, cigarette use, occupation, and family history of chronic liver disease were obtained using an interviewer-administered questionnaire. When the HBV surface antigen (HBsAg)-negative subjects without history of tank-cleaning were used as the reference, the HBsAg-negative subjects with history of tank-cleaning demonstrated a 4.0-fold greater risk of liver cancer (95% confidence interval: 95% CI = 0.2-69.1). The HBsAg carriers without history of tank-cleaning revealed a 25.7-fold greater risk of liver cancer (95% CI = 2.9-229.4). Whereas the HBsAg carriers with history of tank-cleaning revealed the greatest risk (matched odds ratio (ORm) 396.0, 95% CI = 22.6 -infinity) of developing liver cancer among subjects with different VCM-exposure status and HBsAg status categories. Further analysis showed the interaction term was significant (P < .01). Therefore, our results suggest an interaction between occupational VCM exposure and HBV infection for the development of liver cancer.

Current insights into the molecular systems pharmacology of lncRNA-miRNA regulatory interactions and implications in cancer translational medicine

Directory of Open Access Journals (Sweden)

Sujit Nair

2016-04-01

Full Text Available In recent times, the role(s of microRNAs (miRNAs and long noncoding RNAs (lncRNAs in the pathogenesis of various cancers has received great attention. Indeed, there is also a growing recognition of regulatory RNA cross-talk, i.e., lncRNA-miRNA interactions, that may modulate various events in carcinogenesis and progression to metastasis. This review summarizes current evidence in the literature of lncRNA-miRNA interactions in various cancers such as breast, liver, stomach, lung, prostate, bladder, colorectal, blood, brain, skin, kidney, cervical, laryngeal, gall bladder, and bone. Further, the potential prognostic and theragnostic clinical applications of lncRNA-miRNA interactions in cancer are discussed along with an overview of noncoding RNA (ncRNA-based studies that were presented at the American Society of Clinical Oncology (ASCO 2015. Interestingly, the last decade has seen tremendous innovation, as well as increase in complexity, of the cancer biological network(s from mRNA- to miRNA- and lncRNA-based networks. Thus, biological networks devoted to understanding regulatory interactions between these ncRNAs would be the next frontier in better elucidating the contributions of lncRNA-miRNA interactions in cancer. Herein, a cancer biological network of lncRNA-miRNA interactions is presented wherein “edges” connect interacting lncRNA-miRNA pairs, with each ncRNA serving as a discrete “node” of the network. In conclusion, the untapped potential of lncRNA-miRNA interactions in terms of its diagnostic, prognostic and therapeutic potential as targets for clinically actionable intervention as well as biomarker validation in discovery pipelines remains to be explored. Future research will likely harness this potential so as to take us closer to the goal of “precision” and “personalized medicine” which is tailor-made to the unique needs of each cancer patient, and is clearly the way forward going into the future.

Prognostic significance of Traf2- and Nck- interacting kinase (TNIK) in colorectal cancer

International Nuclear Information System (INIS)

Takahashi, Hidenori; Ishikawa, Toshiaki; Ishiguro, Megumi; Okazaki, Satoshi; Mogushi, Kaoru; Kobayashi, Hirotoshi; Iida, Satoru; Mizushima, Hiroshi; Tanaka, Hiroshi; Uetake, Hiroyuki; Sugihara, Kenichi

2015-01-01

The potential of expression profiling using microarray analysis as a tool to predict the prognosis for different types of cancer has been realized. This study aimed to identify a novel biomarker for colorectal cancer (CRC). The expression profiles of cancer cells in 152 patients with stage I-III CRC were examined using microarray analysis. High expression in CRC cells, especially in patients with distant recurrences, was a prerequisite to select candidate genes. Thus, we identified seventeen candidate genes, and selected Traf2- and Nck-interacting kinase (TNIK), which was known to be associated with progression in CRC through Wnt signaling pathways. We analyzed the protein expression of TNIK using immunohistochemistry (IHC) and investigated the relationship between protein expression and patient characteristics in 220 stage I-III CRC patients. Relapse-free survival was significantly worse in the TNIK high expression group than in the TNIK low expression group in stage II (p = 0.028) and stage III (p = 0.006) patients. In multivariate analysis, high TNIK expression was identified as a significant independent risk factor of distant recurrence in stage III patients. This study is the first to demonstrate the prognostic significance of intratumoral TNIK protein expression in clinical tissue samples of CRC, in that high expression of TNIK protein in primary tumors was associated with distant recurrence in stage II and III CRC patients. This TNIK IHC study might contribute to practical decision-making in the treatment of these patients. The online version of this article (doi:10.1186/s12885-015-1783-y) contains supplementary material, which is available to authorized users

Case-only study of interactions between metabolic enzymes and smoking in colorectal cancer

International Nuclear Information System (INIS)

Fan, Chunhong; Jin, Mingjuan; Chen, Kun; Zhang, Yongjing; Zhang, Shuangshuang; Liu, Bing

2007-01-01

Gene-gene and gene-environment interactions involved in the metabolism of carcinogens may increase the risk of cancer. Our objective was to measure the interactions between common polymorphisms of P450 (CYP1A2, CYP1B1, CYP2E1), GSTM1 and T1, SULT1A1 and cigarette smoking in colorectal cancer (CRC). A case-only design was conducted in a Chinese population including 207 patients with sporadic CRC. Unconditional logistic regression analysis was performed adjusting for age, gender, alcohol consumption, and cigarette smoking. The interaction odds ratio (COR) for the gene-gene interaction between CYP1B1 1294G and SULT1A1 638A allele was 2.68 (95% CI: 1.16–6.26). The results of the gene-environment analyses revealed that an interaction existed between cigarette smoking and the CYP1B1 1294G allele for CRC (COR = 2.62, 95%CI: 1.01–6.72), the COR for the interaction of CYP1B1 1294G and smoking history > 35 pack-years was 3.47 (95%CI: 1.12–10.80). No other significant gene-gene and gene-environment interactions were observed. Our results showed that the interaction between polymorphisms in CYP1B1 1294G and SULT1A1*2 may play a significant role on CRC in the Chinese population. Also, it is suggested that the association between cigarette smoking and CRC could be differentiated by the CYP1B1 1294G allele

Host microenvironment in breast cancer development: Inflammatory cells, cytokines and chemokines in breast cancer progression: reciprocal tumor–microenvironment interactions

International Nuclear Information System (INIS)

Ben-Baruch, A

2003-01-01

A comprehensive overview of breast cancer development and progression suggests that the process is influenced by intrinsic properties of the tumor cells, as well as by microenvironmental factors. Indeed, in breast carcinoma, an intensive interplay exists between the tumor cells on one hand, and inflammatory cells/cytokines/chemokines on the other. The purpose of the present review is to outline the reciprocal interactions that exist between these different elements, and to shed light on their potential involvement in breast cancer development and progression

Mouth self-examination to improve oral cancer awareness and early detection in a high-risk population.

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Elango, Kalavathy Jayapal; Anandkrishnan, Nitin; Suresh, Amritha; Iyer, Subramania K; Ramaiyer, Sundaram Karimassery; Kuriakose, Moni Abraham

2011-07-01

Oral cancer is a potentially preventable disease due to its association with well-known risk factors and easy detectability. There is a significant deficiency in the awareness of oral cancer and its risk factors among the public. Raising public awareness could effectively contribute to achieving a significant reduction in the incidence of oral cancer. The objective of this study was to evaluate the effectiveness of mouth self-examination (MSE) in improving the awareness of oral cancer and its risk factors as well as test its feasibility as an oral cancer-screening tool. The study was carried out in a high-risk population of 57,704 from India, of which, 34,766 individuals who have met the eligibility criteria formed the study population. MSE brochures and trained health workers were employed for the purpose of health education and cancer screening. The present study compared their efficacy to detect oral lesions. Subjects with suspicious lesions were referred to the trained oral cancer specialist for confirmation. A questionnaire to assess the awareness of oral cancer and its risk factors was developed and validated. SPSS (v.11.0) was used for data analysis. The program identified 216 cases of potentially malignant lesions as well as three cases of oral cancer. The findings of MSE and health workers showed 72% concordance, while that of health workers and oral cancer specialist showed 100% concordance. MSE had a low sensitivity of 18%, while the specificity was 99.9%. Though the technique identified high-risk lesions such as red patches (66.7%) and non-healing ulcers (42.9%), the detection rate of white patches was low (12.7%). Overall awareness of oral cancer and its risk factors after introduction of MSE program was over 80%; but the compliance to seek treatment was poor (32%). Mouth self-examination may be used as an effective tool to improve the awareness of oral cancer and for the early detection of lesions. Copyright © 2011 Elsevier Ltd. All rights reserved.

Behavioral and physiological reactions in dogs to a veterinary examination: Owner-dog interactions improve canine well-being.

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Csoltova, Erika; Martineau, Michaël; Boissy, Alain; Gilbert, Caroline

2017-08-01

In order to improve well-being of dogs during veterinary visits, we aimed to investigate the effect of human social interactions on behavior and physiology during routine examination. Firstly, we assessed the impact of a standardized veterinary examination on behavioral and physiological indicators of stress in dogs. Secondly, we examined whether the owner's tactile and verbal interactions with the dog influenced behavioral and physiological stress-associated parameters. A randomized within-subjects crossover design was used to examine behavior (n=33), rectal temperature (n=33), heart rate (HR) (n=18), maximal ocular surface temperature (max OST) (n=13) and salivary cortisol concentrations (n=10) in healthy privately owned pet dogs. The study consisted of two experimental conditions: a) "contact" - owner petting and talking to the dog during the examination; b) "non-contact" - owner present during the examination but not allowed to interact with the dog. Our findings showed that the veterinary examinations produced acute stress responses in dogs during both "contact" and "non-contact" conditions, with significant increases in lip licking, HR, and max OST. A significant decrease in attempts to jump off the examination table (p=0.002) was observed during the examination in the "contact" compared to the "non-contact" condition. In addition, interactions of owners showed an attenuating effect on HR (p=0.018) and max OST (p=0.011) in their dogs. The testing order (first vs. second visit) had no impact on behavioral and physiological parameters, suggesting that dogs did not habituate or sensitize to the examination procedure. Moreover, the duration of the owner-dog interactions had no significant impact on the behavioral and physiological responses of their dogs. This study demonstrates that owner-dog interactions improve the well-being of dogs during a veterinary examination. Future research may assist in further understanding the mechanisms associated with reducing

Interaction between alcohol dehydrogenase II gene, alcohol consumption, and risk for breast cancer

OpenAIRE

St?rmer, T; Wang-Gohrke, S; Arndt, V; Boeing, H; Kong, X; Kreienberg, R; Brenner, H

2002-01-01

MaeIII Restriction Fragment Length Polymorphism in exon 3 of the alcohol dehydrogenase II was assessed in serum from 467 randomly selected German women and 278 women with invasive breast cancer to evaluate the interaction between a polymorphism of the alcohol dehydrogenase II gene, alcohol consumption and risk for breast cancer. In both groups, usual consumption of different alcoholic beverages was asked for using semiquantitative food frequency questionnaires. We used multivariable logistic ...

Development of a Combined MR Fingerprinting and Diffusion Examination for Prostate Cancer.

Science.gov (United States)

Yu, Alice C; Badve, Chaitra; Ponsky, Lee E; Pahwa, Shivani; Dastmalchian, Sara; Rogers, Matthew; Jiang, Yun; Margevicius, Seunghee; Schluchter, Mark; Tabayoyong, William; Abouassaly, Robert; McGivney, Debra; Griswold, Mark A; Gulani, Vikas

2017-06-01

Purpose To develop and evaluate an examination consisting of magnetic resonance (MR) fingerprinting-based T1, T2, and standard apparent diffusion coefficient (ADC) mapping for multiparametric characterization of prostate disease. Materials and Methods This institutional review board-approved, HIPAA-compliant retrospective study of prospectively collected data included 140 patients suspected of having prostate cancer. T1 and T2 mapping was performed with fast imaging with steady-state precession-based MR fingerprinting with ADC mapping. Regions of interest were drawn by two independent readers in peripheral zone lesions and normal-appearing peripheral zone (NPZ) tissue identified on clinical images. T1, T2, and ADC were recorded for each region. Histopathologic correlation was based on systematic transrectal biopsy or cognitively targeted biopsy results, if available. Generalized estimating equations logistic regression was used to assess T1, T2, and ADC in the differentiation of (a) cancer versus NPZ, (b) cancer versus prostatitis, (c) prostatitis versus NPZ, and (d) high- or intermediate-grade tumors versus low-grade tumors. Analysis was performed for all lesions and repeated in a targeted biopsy subset. Discriminating ability was evaluated by using the area under the receiver operating characteristic curve (AUC). Results In this study, 109 lesions were analyzed, including 39 with cognitively targeted sampling. T1, T2, and ADC from cancer (mean, 1628 msec ± 344, 73 msec ± 27, and 0.773 × 10 -3 mm 2 /sec ± 0.331, respectively) were significantly lower than those from NPZ (mean, 2247 msec ± 450, 169 msec ± 61, and 1.711 × 10 -3 mm 2 /sec ± 0.269) (P fingerprinting- and diffusion-based examination for quantitative characterization of prostatic tissue. © RSNA, 2017 Online supplemental material is available for this article.

Interaction between body mass index and hormone-receptor status as a prognostic factor in lymph-node-positive breast cancer.

Directory of Open Access Journals (Sweden)

Il Yong Chung

Full Text Available The aim of this study was to determine the relationship between the body mass index (BMI at a breast cancer diagnosis and various factors including the hormone-receptor, menopause, and lymph-node status, and identify if there is a specific patient subgroup for which the BMI has an effect on the breast cancer prognosis. We retrospectively analyzed the data of 8,742 patients with non-metastatic invasive breast cancer from the research database of Asan Medical Center. The overall survival (OS and breast-cancer-specific survival (BCSS outcomes were compared among BMI groups using the Kaplan-Meier method and Cox proportional-hazards regression models with an interaction term. There was a significant interaction between BMI and hormone-receptor status for the OS (P = 0.029, and BCSS (P = 0.013 in lymph-node-positive breast cancers. Obesity in hormone-receptor-positive breast cancer showed a poorer OS (adjusted hazard ratio [HR] = 1.51, 95% confidence interval [CI] = 0.92 to 2.48 and significantly poorer BCSS (HR = 1.80, 95% CI = 1.08 to 2.99. In contrast, a high BMI in hormone-receptor-negative breast cancer revealed a better OS (HR = 0.44, 95% CI = 0.16 to 1.19 and BCSS (HR = 0.53, 95% CI = 0.19 to 1.44. Being underweight (BMI < 18.50 kg/m2 with hormone-receptor-negative breast cancer was associated with a significantly worse OS (HR = 1.98, 95% CI = 1.00-3.95 and BCSS (HR = 2.24, 95% CI = 1.12-4.47. There was no significant interaction found between the BMI and hormone-receptor status in the lymph-node-negative setting, and BMI did not interact with the menopause status in any subgroup. In conclusion, BMI interacts with the hormone-receptor status in a lymph-node-positive setting, thereby playing a role in the prognosis of breast cancer.

Evidence of gene-environment interactions between common breast cancer susceptibility loci and established environmental risk factors

NARCIS (Netherlands)

Nickels, S.; Truong, T.; Hein, R.; Stevens, K.; Buck, K.; Behrens, S.; Eilber, U.; Schmidt, M.; Haberle, L.; Vrieling, A.; Gaudet, M.; Figueroa, J.; Schoof, N.; Spurdle, A.B.; Rudolph, A.; Fasching, P.A.; Hopper, J.L.; Makalic, E.; Schmidt, D.F.; Southey, M.C.; Beckmann, M.W.; Ekici, A.B.; Fletcher, O.; Gibson, L.; Idos, S. Silva; Peto, J.; Humphreys, M.K.; Wang, J; Cordina-Duverger, E.; Menegaux, F.; Nordestgaard, B.G.; Bojesen, S.E.; Lanng, C.; Anton-Culver, H.; Ziogas, A.; Bernstein, L.; Clarke, C.A.; Brenner, H.; Muller, H.; Arndt, V.; Stegmaier, C.; Brauch, H.; Bruning, T.; Harth, V.; Genica, N.; Mannermaa, A.; Kataja, V.; Kosma, V.M.; Hartikainen, J.M.; Lambrechts, D.; Smeets, D.; Neven, P.; Paridaens, R.; Flesch-Janys, D.; Obi, N.; Wang-Gohrke, S.; Couch, F.J.; Olson, J.E.; Vachon, C.M.; Giles, G.G.; Severi, G.; Baglietto, L.; Offit, K.; John, E.M.; Miron, A.; Andrulis, I.L.; Knight, J.A.; Glendon, G.; Mulligan, A.M.; Chanock, S.J.; Lissowska, J.; Liu, J.; Cox, A; Cramp, H.; Connley, D.; Balasubramanian, S.; Dunning, A.M.; Shah, M.; Trentham-Dietz, A.; Newcomb, P.; Titus, L.; Egan, K.; Cahoon, E.K.; Rajaraman, P.; Sigurdson, A.J.; Doody, M.M.; Guenel, P.; Pharoah, P.D.; Schmidt, M.K.; Hall, P.; Easton, D.F.; Garcia-Closas, M.; Milne, R.L.; Chang-Claude, J.; et al.,

2013-01-01

Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cancer.

Unsupportive social interactions and affective states: examining associations of two oxytocin-related polymorphisms.

Science.gov (United States)

McInnis, Opal A; McQuaid, Robyn J; Matheson, Kimberly; Anisman, Hymie

2017-01-01

Two single-nucleotide polymorphisms (SNPs) on oxytocin-related genes, specifically the oxytocin receptor (OXTR) rs53576 and the CD38 rs3796863 variants, have been associated with alterations in prosocial behaviors. A cross-sectional study was conducted among undergraduate students (N = 476) to examine associations between the OXTR and CD38 polymorphisms and unsupportive social interactions and mood states. Results revealed no association between perceived levels of unsupportive social interactions and the OXTR polymorphism. However, A carriers of the CD38 polymorphism, a variant previously associated with elevated oxytocin, reported greater perceived peer unsupportive interactions compared to CC carriers. As expected, perceived unsupportive interactions from peers was associated with greater negative affect, which was moderated by the CD38 polymorphism. Specifically, this relation was stronger among CC carriers of the CD38 polymorphism (a variant thought to be linked to lower oxytocin). When examining whether the OXTR polymorphism moderated the relation between unsupportive social interactions from peers and negative affect there was a trend toward significance, however, this did not withstand multiple testing corrections. These findings are consistent with the perspective that a variant on an oxytocin polymorphism that may be tied to lower oxytocin is related to poor mood outcomes in association with negative social interactions. At the same time, having a genetic constitution presumed to be associated with higher oxytocin was related to increased perceptions of unsupportive social interactions. These seemingly paradoxical findings could be related to previous reports in which variants associated with prosocial behaviors were also tied to relatively more effective coping styles to deal with challenges.

Multiple analytical approaches reveal distinct gene-environment interactions in smokers and non smokers in lung cancer.

Directory of Open Access Journals (Sweden)

Rakhshan Ihsan

Full Text Available Complex disease such as cancer results from interactions of multiple genetic and environmental factors. Studying these factors singularly cannot explain the underlying pathogenetic mechanism of the disease. Multi-analytical approach, including logistic regression (LR, classification and regression tree (CART and multifactor dimensionality reduction (MDR, was applied in 188 lung cancer cases and 290 controls to explore high order interactions among xenobiotic metabolizing genes and environmental risk factors. Smoking was identified as the predominant risk factor by all three analytical approaches. Individually, CYP1A1*2A polymorphism was significantly associated with increased lung cancer risk (OR = 1.69;95%CI = 1.11-2.59,p = 0.01, whereas EPHX1 Tyr113His and SULT1A1 Arg213His conferred reduced risk (OR = 0.40;95%CI = 0.25-0.65,p<0.001 and OR = 0.51;95%CI = 0.33-0.78,p = 0.002 respectively. In smokers, EPHX1 Tyr113His and SULT1A1 Arg213His polymorphisms reduced the risk of lung cancer, whereas CYP1A1*2A, CYP1A1*2C and GSTP1 Ile105Val imparted increased risk in non-smokers only. While exploring non-linear interactions through CART analysis, smokers carrying the combination of EPHX1 113TC (Tyr/His, SULT1A1 213GG (Arg/Arg or AA (His/His and GSTM1 null genotypes showed the highest risk for lung cancer (OR = 3.73;95%CI = 1.33-10.55,p = 0.006, whereas combined effect of CYP1A1*2A 6235CC or TC, SULT1A1 213GG (Arg/Arg and betel quid chewing showed maximum risk in non-smokers (OR = 2.93;95%CI = 1.15-7.51,p = 0.01. MDR analysis identified two distinct predictor models for the risk of lung cancer in smokers (tobacco chewing, EPHX1 Tyr113His, and SULT1A1 Arg213His and non-smokers (CYP1A1*2A, GSTP1 Ile105Val and SULT1A1 Arg213His with testing balance accuracy (TBA of 0.6436 and 0.6677 respectively. Interaction entropy interpretations of MDR results showed non-additive interactions of tobacco chewing with

Structural effects and competition mechanisms targeting the interactions between p53 and MDM2 for cancer therapy

Science.gov (United States)

Liu, Shu-Xia; Geng, Yi-Zhao; Yan, Shi-Wei

2017-06-01

Approximately half of all human cancers show normal TP53 gene expression but aberrant overexpression of MDM2 and/or MDMX. This fact suggests a promising cancer therapeutic strategy in targeting the interactions between p53 and MDM2/MDMX. To help realize the goal of developing effective inhibitors to disrupt the p53-MDM2/MDMX interaction, we systematically investigated the structural and interaction characteristics of p53 with inhibitors of its interactions with MDM2 and MDMX from an atomistic perspective using stochastic molecular dynamics simulations. We found that some specific α helices in the structures of MDM2 and MDMX play key roles in their binding to inhibitors, and that the hydrogen bond formed by the Trp23 residue of p53 with its counterpart in MDM2 or MDMX determines the dynamic competition processes of the disruption of the MDM2-p53 interaction and replacement of p53 from the MDM2-p53 complex in vivo. The results reported in this paper are expected to provide basic information for designing functional inhibitors and realizing new strategies of cancer gene therapy.

Rational Design of Multifunctional Gold Nanoparticles via Host-Guest Interaction for Cancer-Targeted Therapy.

Science.gov (United States)

Chen, Wei-Hai; Lei, Qi; Luo, Guo-Feng; Jia, Hui-Zhen; Hong, Sheng; Liu, Yu-Xin; Cheng, Yin-Jia; Zhang, Xian-Zheng

2015-08-12

A versatile gold nanoparticle-based multifunctional nanocomposite AuNP@CD-AD-DOX/RGD was constructed flexibly via host-guest interaction for targeted cancer chemotherapy. The pH-sensitive anticancer prodrug AD-Hyd-DOX and the cancer-targeted peptide AD-PEG8-GRGDS were modified on the surface of AuNP@CD simultaneously, which endowed the resultant nanocomposite with the capability to selectively eliminate cancer cells. In vitro studies indicated that the AuNP@CD-AD-DOX/RGD nanocomposite was preferentially uptaken by cancer cells via receptor-mediated endocytosis. Subsequently, anticancer drug DOX was released rapidly upon the intracellular trigger of the acid microenvirenment of endo/lysosomes, inducing apoptosis in cancer cells. As the ideal drug nanocarrier, the multifunctional gold nanoparticles with the active targeting and controllable intracellular release ability hold the great potential in cancer therapy.

Collaborative Encoding and Memory Accuracy: Examining the Effects of Interactive Components of Co-Construction Processes

Science.gov (United States)

Foley, Mary Ann; Fried, Adina Rachel; Cowan, Emily; Bays, Rebecca Brooke

2014-01-01

In 2 experiments, the effect of collaborative encoding on memory was examined by testing 2 interactive components of co-construction processes. One component focused on the nature of the interactive exchange between collaborators: As the partners worked together to create descriptions about ways to interact with familiar objects, constraints were…

Heavy smoking history interacts with chemoradiotherapy for esophageal cancer prognosis. A retrospective study

International Nuclear Information System (INIS)

Shitara, Kohei; Hatooka, Shunzo; Matsuo, Keitaro

2010-01-01

Smoking is a well-known risk factor for esophageal cancer. However, there are few reports that directly evaluate smoking as a prognostic factor for esophageal cancer. Moreover, scarce evidence is available on whether smoking interacts with major treatment modalities of esophageal cancer. In this study we retrospectively analyzed 364 patients with esophageal squamous cell cancer who were treated between 2001 and 2005 at our institution. Background characteristics, including smoking history, were analyzed as potential prognostic factors. Of the 363 patients, 76 patients (20.9%) were non-smokers or light smokers (non-heavy), whereas 287 patients (79.1%) were heavy smokers. The 5-year survival rate for non-heavy smokers and heavy smokers was 61.8% (95% confidence interval [CI]: 49.1-72.2) vs 44.6% (95% CI: 38.2-50.9), respectively. In a multivariate Cox model (adjusted for age, gender, performance status, alcohol consumption, histology, tumor length, International Union Against Cancer [UICC] stage, and treatment), the hazard ratio for heavy smokers in comparison with non-heavy smokers was 1.73 (95% CI: 1.12-2.68; P=0.013). When we stratified by treatment method, heavy smoking was significantly associated with poor survival only in patients treated by chemoradiotherapy (hazard ratio, 2.43; 95% CI: 1.38-4.27; P=0.002). More importantly, a statistically significant interaction between heavy smoking history and treatment modality was observed (P=0.041). Our results indicated that smoking history is strongly associated with poor prognosis in patients with esophageal cancer, especially those treated by chemoradiotherapy. Further investigation is warranted to explain this different prognosis. (author)

77 FR 31041 - Draft Standards and Best Practices for Interaction Between Medical Examiner/Coroner and Organ and...

Science.gov (United States)

2012-05-24

... Best Practices for Interaction Between Medical Examiner/Coroner and Organ and Tissue Procurement... titled ``Organ and Tissue Procurement Committee Standards and Best Practices for Interaction Between Medical Examiner/Coroner Offices and Organ Tissue Procurement Organizations'' from May 12, 2012, to June...

Cancer Center Clinic and Research Team Perceptions of Identity and Interactions.

Science.gov (United States)

Reimer, Torsten; Lee, Simon J Craddock; Garcia, Sandra; Gill, Mary; Duncan, Tobi; Williams, Erin L; Gerber, David E

2017-12-01

Conduct of cancer clinical trials requires coordination and cooperation among research and clinic teams. Diffusion of and confusion about responsibility may occur if team members' perceptions of roles and objectives do not align. These factors are critical to the success of cancer centers but are poorly studied. We developed a survey adapting components of the Adapted Team Climate Inventory, Measure of Team Identification, and Measure of In-Group Bias. Surveys were administered to research and clinic staff at a National Cancer Institute-designated comprehensive cancer center. Data were analyzed using descriptive statistics, t tests, and analyses of variance. Responses were received from 105 staff (clinic, n = 55; research, n = 50; 61% response rate). Compared with clinic staff, research staff identified more strongly with their own group ( P teams, we also identified key differences, including perceptions of goal clarity and sharing, understanding and alignment with cancer center goals, and importance of outcomes. Future studies should examine how variation in perceptions and group dynamics between clinic and research teams may impact function and processes of cancer care.

Lipid raft association restricts CD44-ezrin interaction and promotion of breast cancer cell migration.

LENUS (Irish Health Repository)

Donatello, Simona

2012-12-01

Cancer cell migration is an early event in metastasis, the main cause of breast cancer-related deaths. Cholesterol-enriched membrane domains called lipid rafts influence the function of many molecules, including the raft-associated protein CD44. We describe a novel mechanism whereby rafts regulate interactions between CD44 and its binding partner ezrin in migrating breast cancer cells. Specifically, in nonmigrating cells, CD44 and ezrin localized to different membranous compartments: CD44 predominantly in rafts, and ezrin in nonraft compartments. After the induction of migration (either nonspecific or CD44-driven), CD44 affiliation with lipid rafts was decreased. This was accompanied by increased coprecipitation of CD44 and active (threonine-phosphorylated) ezrin-radixin-moesin (ERM) proteins in nonraft compartments and increased colocalization of CD44 with the nonraft protein, transferrin receptor. Pharmacological raft disruption using methyl-β-cyclodextrin also increased CD44-ezrin coprecipitation and colocalization, further suggesting that CD44 interacts with ezrin outside rafts during migration. Conversely, promoting CD44 retention inside lipid rafts by pharmacological inhibition of depalmitoylation virtually abolished CD44-ezrin interactions. However, transient single or double knockdown of flotillin-1 or caveolin-1 was not sufficient to increase cell migration over a short time course, suggesting complex crosstalk mechanisms. We propose a new model for CD44-dependent breast cancer cell migration, where CD44 must relocalize outside lipid rafts to drive cell migration. This could have implications for rafts as pharmacological targets to down-regulate cancer cell migration.

Lipid Raft Association Restricts CD44-Ezrin Interaction and Promotion of Breast Cancer Cell Migration

Science.gov (United States)

Donatello, Simona; Babina, Irina S.; Hazelwood, Lee D.; Hill, Arnold D.K.; Nabi, Ivan R.; Hopkins, Ann M.

2012-01-01

Cancer cell migration is an early event in metastasis, the main cause of breast cancer-related deaths. Cholesterol-enriched membrane domains called lipid rafts influence the function of many molecules, including the raft-associated protein CD44. We describe a novel mechanism whereby rafts regulate interactions between CD44 and its binding partner ezrin in migrating breast cancer cells. Specifically, in nonmigrating cells, CD44 and ezrin localized to different membranous compartments: CD44 predominantly in rafts, and ezrin in nonraft compartments. After the induction of migration (either nonspecific or CD44-driven), CD44 affiliation with lipid rafts was decreased. This was accompanied by increased coprecipitation of CD44 and active (threonine-phosphorylated) ezrin-radixin-moesin (ERM) proteins in nonraft compartments and increased colocalization of CD44 with the nonraft protein, transferrin receptor. Pharmacological raft disruption using methyl-β-cyclodextrin also increased CD44-ezrin coprecipitation and colocalization, further suggesting that CD44 interacts with ezrin outside rafts during migration. Conversely, promoting CD44 retention inside lipid rafts by pharmacological inhibition of depalmitoylation virtually abolished CD44-ezrin interactions. However, transient single or double knockdown of flotillin-1 or caveolin-1 was not sufficient to increase cell migration over a short time course, suggesting complex crosstalk mechanisms. We propose a new model for CD44-dependent breast cancer cell migration, where CD44 must relocalize outside lipid rafts to drive cell migration. This could have implications for rafts as pharmacological targets to down-regulate cancer cell migration. PMID:23031255

Early Prostate Cancer: Hedonic Prices Model of Provider-Patient Interactions and Decisions

International Nuclear Information System (INIS)

Jani, Ashesh B.; Hellman, Samuel

2008-01-01

Purpose: To determine the relative influence of treatment features and treatment availabilities on final treatment decisions in early prostate cancer. Methods and Materials: We describe and apply a model, based on hedonic prices, to understand provider-patient interactions in prostate cancer. This model included four treatments (observation, external beam radiotherapy, brachytherapy, and prostatectomy) and five treatment features (one efficacy and four treatment complication features). We performed a literature search to estimate (1) the intersections of the 'bid' functions and 'offer' functions with the price function along different treatment feature axes, and (2) the treatments actually rendered in different patient subgroups based on age. We performed regressions to determine the relative weight of each feature in the overall interaction and the relative availability of each treatment modality to explain differences between observed vs. predicted use of different modalities in different patient subpopulations. Results: Treatment efficacy and potency preservation are the major factors influencing decisions for young patients, whereas preservation of urinary and rectal function is much more important for very elderly patients. Referral patterns seem to be responsible for most of the deviations of observed use of different treatments from those predicted by idealized provider-patient interactions. Specifically, prostatectomy is used far more commonly in young patients and radiotherapy and observation used far more commonly in elderly patients than predicted by a uniform referral pattern. Conclusions: The hedonic prices approach facilitated identifying the relative importance of treatment features and quantification of the impact of the prevailing referral pattern on prostate cancer treatment decisions

Small molecule inhibitors of ERCC1-XPF protein-protein interaction synergize alkylating agents in cancer cells.

Science.gov (United States)

Jordheim, Lars Petter; Barakat, Khaled H; Heinrich-Balard, Laurence; Matera, Eva-Laure; Cros-Perrial, Emeline; Bouledrak, Karima; El Sabeh, Rana; Perez-Pineiro, Rolando; Wishart, David S; Cohen, Richard; Tuszynski, Jack; Dumontet, Charles

2013-07-01

The benefit of cancer chemotherapy based on alkylating agents is limited because of the action of DNA repair enzymes, which mitigate the damage induced by these agents. The interaction between the proteins ERCC1 and XPF involves two major components of the nucleotide excision repair pathway. Here, novel inhibitors of this interaction were identified by virtual screening based on available structures with use of the National Cancer Institute diversity set and a panel of DrugBank small molecules. Subsequently, experimental validation of the in silico screening was undertaken. Top hits were evaluated on A549 and HCT116 cancer cells. In particular, the compound labeled NSC 130813 [4-[(6-chloro-2-methoxy-9-acridinyl)amino]-2-[(4-methyl-1-piperazinyl)methyl

Interaction of cytochrome P4501A1 genotypes with other risk factors and susceptibility to lung cancer

Energy Technology Data Exchange (ETDEWEB)

Shah, Parag P.; Singh, Arvind P.; Singh, Madhu; Mathur, Neeraj [Developmental Toxicology Division, Industrial Toxicology Research Centre, P.O. Box 80, M.G. Marg, Lucknow 226001 (India); Pant, Mohan C. [Department of Radiotherapy, King George' s Medical University, Shahmina Road, Lucknow 226001 (India); Mishra, Bhartendu N. [Department of Biotechnology, IET, Sitapur Road, Lucknow 226021 (India); Parmar, Devendra [Developmental Toxicology Division, Industrial Toxicology Research Centre, P.O. Box 80, M.G. Marg, Lucknow 226001 (India)], E-mail: parmar_devendra@hotmail.com

2008-03-01

Lung cancer is the most common cause of death throughout the world with cigarette smoking being established as the major etiological factor in lung cancer. Since not much information is available regarding the polymorphism in drug metabolizing enzymes and lung cancer risk in the Indian population, the present case-control study attempted to investigate the association of polymorphisms in cytochrome P450 1A1 (CYP1A1) and glutathione-S-transferase M1 (GSTM1) with risk to squamous cell carcinoma of lung malignancy. Patients suffering from lung cancer (n = 200) and visiting OPD facility of Department of Radiotherapy, King George's Medical University, Lucknow, were included in the study. Equal number (n = 200) of age and sex matched healthy individuals were also enrolled in the study. Our data revealed that the variant genotypes of CYP1A1*2A, CYP1A1*2C and CYP1A1*4 were found to be over represented in the lung cancer patients when compared to controls. CYP1A1*2A variant genotypes (combined heterozygous and mutant genotypes) revealed significant association towards the lung cancer risk (OR: 1.93, 95%CI: 1.28-2.89, p = 0.002). Likewise, GSTM1 null genotypes were found to be over represented in patients when compared to controls. Haplotype analysis revealed that CYP1A1 haplotype, C-G-C increased the lung cancer risk (OR: 3.90, 95%CI: 1.00-15.04, p = 0.025) in the patients. The lung cancer risk was increased several two-to fourfold in the patients carrying the genotype combinations of CYP1A1*2A and GSTM1 suggesting the role of gene-gene interaction in lung cancer. Cigarette smoking or tobacco chewing or alcohol consumption was also found to interact with CYP1A1 genotypes in increasing the risk to lung cancer further demonstrating the role of gene-environment interaction in development of lung cancer.

Interaction of cytochrome P4501A1 genotypes with other risk factors and susceptibility to lung cancer

International Nuclear Information System (INIS)

Shah, Parag P.; Singh, Arvind P.; Singh, Madhu; Mathur, Neeraj; Pant, Mohan C.; Mishra, Bhartendu N.; Parmar, Devendra

2008-01-01

Lung cancer is the most common cause of death throughout the world with cigarette smoking being established as the major etiological factor in lung cancer. Since not much information is available regarding the polymorphism in drug metabolizing enzymes and lung cancer risk in the Indian population, the present case-control study attempted to investigate the association of polymorphisms in cytochrome P450 1A1 (CYP1A1) and glutathione-S-transferase M1 (GSTM1) with risk to squamous cell carcinoma of lung malignancy. Patients suffering from lung cancer (n = 200) and visiting OPD facility of Department of Radiotherapy, King George's Medical University, Lucknow, were included in the study. Equal number (n = 200) of age and sex matched healthy individuals were also enrolled in the study. Our data revealed that the variant genotypes of CYP1A1*2A, CYP1A1*2C and CYP1A1*4 were found to be over represented in the lung cancer patients when compared to controls. CYP1A1*2A variant genotypes (combined heterozygous and mutant genotypes) revealed significant association towards the lung cancer risk (OR: 1.93, 95%CI: 1.28-2.89, p = 0.002). Likewise, GSTM1 null genotypes were found to be over represented in patients when compared to controls. Haplotype analysis revealed that CYP1A1 haplotype, C-G-C increased the lung cancer risk (OR: 3.90, 95%CI: 1.00-15.04, p = 0.025) in the patients. The lung cancer risk was increased several two-to fourfold in the patients carrying the genotype combinations of CYP1A1*2A and GSTM1 suggesting the role of gene-gene interaction in lung cancer. Cigarette smoking or tobacco chewing or alcohol consumption was also found to interact with CYP1A1 genotypes in increasing the risk to lung cancer further demonstrating the role of gene-environment interaction in development of lung cancer

Interaction of celecoxib with different anti-cancer drugs is antagonistic in breast but not in other cancer cells

International Nuclear Information System (INIS)

El-Awady, Raafat A.; Saleh, Ekram M.; Ezz, Marwa; Elsayed, Abeer M.

2011-01-01

Celecoxib, an inhibitor of cyclooxygenase-2, is being investigated for enhancement of chemotherapy efficacy in cancer clinical trials. This study investigates the ability of cyclooxygenase-2 inhibitors to sensitize cells from different origins to several chemotherapeutic agents. The effect of the drug's mechanism of action and sequence of administration are also investigated. The sensitivity, cell cycle, apoptosis and DNA damage of five different cancer cell lines (HeLa, HCT116, HepG2, MCF7 and U251) to 5-FU, cisplatin, doxorubicin and etoposide ± celecoxib following different incubation schedules were analyzed. We found antagonism between celecoxib and the four drugs in the breast cancer cells MCF7 following all incubation schedules and between celecoxib and doxorubicin in all cell lines except for two combinations in HCT116 cells. Celecoxib with the other three drugs in the remaining four cell lines resulted in variable interactions. Mechanistic investigations revealed that celecoxib exerts different molecular effects in different cells. In some lines, it abrogates the drug-induced G2/M arrest enhancing pre-mature entry into mitosis with damaged DNA thus increasing apoptosis and resulting in synergism. In other cells, it enhances drug-induced G2/M arrest allowing time to repair drug-induced DNA damage before entry into mitosis and decreasing cell death resulting in antagonism. In some synergistic combinations, celecoxib-induced abrogation of G2/M arrest was not associated with apoptosis but permanent arrest in G1 phase. These results, if confirmed in-vivo, indicate that celecoxib is not a suitable chemosensitizer for breast cancer or with doxorubicin for other cancers. Moreover, combination of celecoxib with other drugs should be tailored to the tumor type, drug and administration schedule. - Graphical abstract: Display Omitted Highlights: → Celecoxib may enhance effects of anticancer drugs. → Its combination with four drugs was tested in five cancer cell

Paracrine interactions of cancer-associated fibroblasts, macrophages and endothelial cells: tumor allies and foes.

Science.gov (United States)

Ronca, Roberto; Van Ginderachter, Jo A; Turtoi, Andrei

2018-01-01

Tumor stroma is composed of many cellular subtypes, of which the most abundant are fibroblasts, macrophages and endothelial cells. During the process of tissue injury, these three cellular subtypes must coordinate their activity to efficiently contribute to tissue regeneration. In tumor, this mechanism is hijacked by cancer cells, which rewire the interaction of stromal cells to benefit tumor development. The present review aims at summarizing most relevant information concerning both pro-tumorigenic and anti-tumorigenic actions implicating the three stromal cell subtypes as well as their mutual interactions. Although stromal cells are generally regarded as tumor-supportive and at will manipulated by cancer cells, several novel studies point at many defaults in cancer cell-mediated stromal reprograming. Indeed, parts of initial tissue-protective and homeostatic functions of the stromal cells remain in place even after tumor development. Both tumor-supportive and tumor-suppressive functions have been well described for macrophages, whereas similar results are emerging for fibroblasts and endothelial cells. Recent success of immunotherapies have finally brought the long awaited proof that stroma is key for efficient tumor targeting. However, a better understanding of paracrine stromal interactions is needed in order to encourage drug development not only aiming at disruption of tumor-supportive communication but also re-enforcing, existing, tumor-suppressive mechanisms.

Screening for lung cancer with digital chest radiography: sensitivity and number of secondary work-up CT examinations

NARCIS (Netherlands)

de Hoop, Bartjan; Schaefer-Prokop, Cornelia; Gietema, Hester A.; de Jong, Pim A.; van Ginneken, Bram; van Klaveren, Rob J.; Prokop, Mathias

2010-01-01

To estimate the performance of digital chest radiography for detection of lung cancer. The study had ethics committee approval, and a nested case-control design was used and included 55 patients with lung cancer detected at computed tomography (CT) and confirmed with histologic examination and a

Effects of Two Testicular Cancer Education Programs on Self-Examination Knowledge and Attitudes among College-Aged Men.

Science.gov (United States)

Marty, Phillip J.; McDermott, Robert J.

1985-01-01

This study compared instructional outcomes of two education programs about testicular cancer and testicular self-examination. Instruction facilitated by a former testicular cancer patient was compared to information provided by printed materials. There was no difference in information dissemination, but possible differences in attitude resulted.…

A novel environmental exposure index and its interaction with familial susceptibility on oral cancer in non-smokers and non-drinkers: a case-control study.

Science.gov (United States)

Yan, Lingjun; Chen, Fa; He, Baochang; Liu, Fengqiong; Liu, Fangping; Huang, Jiangfeng; Wu, Junfeng; Lin, Lisong; Qiu, Yu; Cai, Lin

2017-04-01

The objective of this study was to explore the collective effect of environmental factors and its interaction with familial susceptibility on oral cancer among non-smokers and non-drinkers (NSND). A hospital-based case-control study, including 319 oral cancer patients and 994 frequency-matched controls, was conducted in Fujian, China. We raised a weighed environmental exposure index according to nine significant environmental factors obtained from multivariable logistic regression model. And then, the index was classified into three categories according to the tertiles of controls (2.43). Multiplicative and additive interactions were evaluated between environmental exposure index and family cancer history. Our results showed that environmental exposure index was associated with an increased risk of oral cancer especially for those with family cancer history. Compared to subjects with low environmental exposure index and without family cancer history, those with high index and family cancer history showed the highest magnitude of OR in oral cancer risk (OR 10.40, 95% CI 5.46-19.80). Moreover, there was a multiplicative interaction between environmental exposure index and family cancer history for the risk of oral cancer (P oral cancer among NSND and may interact with family cancer history. Further studies are warranted to explore the underlying mechanisms.

Cancer patients undertaking bone scans in a department of Nuclear Medicine have significant stress related to the examination

International Nuclear Information System (INIS)

Sioka, C.; Manetou, M.; Dimakopoulos, N.; Christidi, S.; Kouraklis, G.

2005-01-01

Bone scanning is a standard screening procedure for evaluation of metastases in cancer patient. In addition to the staging procedures, bone scan is a valuable test for deciding palliative therapeutic options in selected patients. The aim of this study was to investigate if patients with cancer who were undertaking routine bone scans had any stress related to the test. We asked 83 consecutive patients with various types of cancer if they had anxiety just prior to undergoing the test. Overall, we found that 53 (64%) patients had increased anxiety related to the examination and 30 (36%) patients did not. Among the 53 patients who were anxious about the bone scan, 32 were concerned about the results of the examination, 13 worried about the effects of the radiation, 4 were anxious for both results/radiation, and 4 patients had stress but could not specify the reason. Among the 32 patients who were concerned about the results of the examination, 15 were having their first bone scans, while 17 had already undergone the procedure before. Among the 13 patients who were mainly concerned about the risks of the radiation exposure during the test, 9 were having bone scans for the first time. Out of the 4 patients who feared both the results and radiation, 3 were having bone scans for the first time and 1 had it for several times. Finally, out of the 4 patients who had anxiety about the test but could not identify the reason, 3 were having bone scans for the first time and one had the test before but was claustrophobic. Our findings indicate that most patients (64%) with cancer who underwent a routine bone scan to check for metastatic disease had intense stress related either to the results or the side effects of the examination. However, there were more patients who were concerned about the results of the test rather than the effects of radiation. Among the patients who feared the effects of radioactivity most were having the test for the first time. A previous study in a

Bayesian network modelling on data from fine needle aspiration cytology examination for breast cancer diagnosis

OpenAIRE

Ding, Xuemei; Cao, Yi; Zhai, Jia; Maguire, Liam; Li, Yuhua; Yang, Hongqin; Wang, Yuhua; Zeng, Jinshu; Liu, Shuo

2017-01-01

The paper employed Bayesian network (BN) modelling approach to discover causal dependencies among different data features of Breast Cancer Wisconsin Dataset (BCWD) derived from openly sourced UCI repository. K2 learning algorithm and k-fold cross validation were used to construct and optimize BN structure. Compared to Na‹ve Bayes (NB), the obtained BN presented better performance for breast cancer diagnosis based on fine needle aspiration cytology (FNAC) examination. It also showed that, amon...

Emory University: MEDICI (Mining Essentiality Data to Identify Critical Interactions) for Cancer Drug Target Discovery and Development | Office of Cancer Genomics

Science.gov (United States)

The CTD2 Center at Emory University has developed a computational methodology to combine high-throughput knockdown data with known protein network topologies to infer the importance of protein-protein interactions (PPIs) for the survival of cancer cells.  Applying these data to the Achilles shRNA results, the CCLE cell line characterizations, and known and newly identified PPIs provides novel insights for potential new drug targets for cancer therapies and identifies important PPI hubs.

xSyn: A Software Tool for Identifying Sophisticated 3-Way Interactions From Cancer Expression Data

Directory of Open Access Journals (Sweden)

Baishali Bandyopadhyay

2017-08-01

Full Text Available Background: Constructing gene co-expression networks from cancer expression data is important for investigating the genetic mechanisms underlying cancer. However, correlation coefficients or linear regression models are not able to model sophisticated relationships among gene expression profiles. Here, we address the 3-way interaction that 2 genes’ expression levels are clustered in different space locations under the control of a third gene’s expression levels. Results: We present xSyn, a software tool for identifying such 3-way interactions from cancer gene expression data based on an optimization procedure involving the usage of UPGMA (Unweighted Pair Group Method with Arithmetic Mean and synergy. The effectiveness is demonstrated by application to 2 real gene expression data sets. Conclusions: xSyn is a useful tool for decoding the complex relationships among gene expression profiles. xSyn is available at http://www.bdxconsult.com/xSyn.html .

Biopsychosocial problem-related distress in cancer: examining the role of sex and age.

Science.gov (United States)

Clark, Karen; Bergerot, Cristiane Decat; Philip, Errol J; Buga, Sorin; Obenchain, Richard; Loscalzo, Matthew J

2017-10-01

The current study explores how sex and age relate to biopsychosocial distress by applying a large-scale analysis among individuals diagnosed with a variety of cancers. A retrospective study was conducted involving 6462 patients treated for cancer at a National Cancer Institute-designated comprehensive cancer center between 2009 and 2014. Patients were asked to complete the biopsychosocial problem-related distress touchscreen instrument prior to starting treatment as part of their routine clinical care. There was a significant interaction of age and sex on the total number of problems rated as high distress and the total number of problems that prompted a request to talk with a member of the team. Male patients between 18 and 39 reported significantly more problems as high distress than female patients in the same age group (mean = 5.34 and mean = 4.92, respectively; p = 0.005). A similar trend was found where male patients between 18-39 and 40-64 requested to talk with a member of the team significantly more often than female patients in these same age groups (mean = 3.25 and mean = 3.22 vs. mean = 2.70 and mean = 3.07, respectively; p = 0.016). The results of the current study serve to refute generalizations regarding age or gender demographics and support preferences and thus reinforce the need to offer services in the context of cancer in flexible and varied ways. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

The bone morphogenetic protein antagonist gremlin 1 is overexpressed in human cancers and interacts with YWHAH protein

International Nuclear Information System (INIS)

Namkoong, Hong; Shin, Seung Min; Kim, Hyun Kee; Ha, Seon-Ah; Cho, Goang Won; Hur, Soo Young; Kim, Tae Eung; Kim, Jin Woo

2006-01-01

Basic studies of oncogenesis have demonstrated that either the elevated production of particular oncogene proteins or the occurrence of qualitative abnormalities in oncogenes can contribute to neoplastic cellular transformation. The purpose of our study was to identify an unique gene that shows cancer-associated expression, and characterizes its function related to human carcinogenesis. We used the differential display (DD) RT-PCR method using normal cervical, cervical cancer, metastatic cervical tissues, and cervical cancer cell lines to identify genes overexpressed in cervical cancers and identified gremlin 1 which was overexpressed in cervical cancers. We determined expression levels of gremlin 1 using Northern blot analysis and immunohistochemical study in various types of human normal and cancer tissues. To understand the tumorigenesis pathway of identified gremlin 1 protein, we performed a yeast two-hybrid screen, GST pull down assay, and immunoprecipitation to identify gremlin 1 interacting proteins. DDRT-PCR analysis revealed that gremlin 1 was overexpressed in uterine cervical cancer. We also identified a human gremlin 1 that was overexpressed in various human tumors including carcinomas of the lung, ovary, kidney, breast, colon, pancreas, and sarcoma. PIG-2-transfected HEK 293 cells exhibited growth stimulation and increased telomerase activity. Gremlin 1 interacted with homo sapiens tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta polypeptide (14-3-3 eta; YWHAH). YWHAH protein binding site for gremlin 1 was located between residues 61–80 and gremlin 1 binding site for YWHAH was found to be located between residues 1 to 67. Gremlin 1 may play an oncogenic role especially in carcinomas of the uterine cervix, lung, ovary, kidney, breast, colon, pancreas, and sarcoma. Over-expressed gremlin 1 functions by interaction with YWHAH. Therefore, Gremlin 1 and its binding protein YWHAH could be good targets for developing diagnostic and

Identification of BLCAP as a novel STAT3 interaction partner in bladder cancer

DEFF Research Database (Denmark)

Gromova, Irina; Svensson, Sofia; Gromov, Pavel

2017-01-01

Bladder cancer associated protein (Blcap) expression is commonly down-regulated in invasive bladder cancer, and may have prognostic value given that its expression is negatively correlated with patient survival. We have previously investigated the expression patterns and cellular localization...... and canonical signaling pathways. We performed serial immunohistochemistry (IHC) analysis of bladder tissue samples, with serial sections stained with phospho-specific antibodies recognizing key signaling intermediates, such as P-Stat3, P-Akt, and P-Erk1/2, among others, in an immunophenotyping approach we have......, using an in situ proximity ligation assay that Blcap and Stat3 are in close physical proximity of each other in bladder tissue, and that Blcap physically interacts with Stat3 as determined by co-immunoprecipitation of these proteins. Our data indicates that Blcap is a novel Stat3 interaction partner...

ERRα augments HIF-1 signalling by directly interacting with HIF-1α in normoxic and hypoxic prostate cancer cells.

Science.gov (United States)

Zou, Chang; Yu, Shan; Xu, Zhenyu; Wu, Dinglan; Ng, Chi-Fai; Yao, Xiaoqiang; Yew, David T; Vanacker, Jean-Marc; Chan, Franky L

2014-05-01

Adaptation of cancer cells to a hypoxic microenvironment is important for their facilitated malignant growth and advanced development. One major mechanism mediating the hypoxic response involves up-regulation of hypoxia-inducible factor 1 (HIF-1) expression, which controls reprogramming of energy metabolism and angiogenesis. Oestrogen-related receptor-α (ERRα) is a pivotal regulator of cellular energy metabolism and many biosynthetic pathways, and has also been proposed to be an important factor promoting the Warburg effect in advanced cancer. We and others have previously shown that ERRα expression is increased in prostate cancer and is also a prognostic marker. Here we show that ERRα is oncogenic in prostate cancer and also a key hypoxic growth regulator. ERRα-over-expressing prostate cancer cells were more resistant to hypoxia and showed enhanced HIF-1α protein expression and HIF-1 signalling. These effects could also be observed in ERRα-over-expressing cells grown under normoxia, suggesting that ERRα could function to pre-adapt cancer cells to meet hypoxia stress. Immunoprecipitation and FRET assays indicated that ERRα could physically interact with HIF-1α via its AF-2 domain. A ubiquitination assay showed that this ERRα-HIF-1α interaction could inhibit ubiquitination of HIF-1α and thus reduce its degradation. Such ERRα-HIF-1α interaction could be attenuated by XCT790, an ERRα-specific inverse agonist, resulting in reduced HIF-1α levels. In summary, we show that ERRα can promote the hypoxic growth adaptation of prostate cancer cells via a protective interaction with HIF-1α, suggesting ERRα as a potential therapeutic target for cancer treatment. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

A multimedia interactive education system for prostate cancer patients: development and preliminary evaluation.

Science.gov (United States)

Diefenbach, Michael A; Butz, Brian P

2004-01-21

A cancer diagnosis is highly distressing. Yet, to make informed treatment choices patients have to learn complicated disease and treatment information that is often fraught with medical and statistical terminology. Thus, patients need accurate and easy-to-understand information. To introduce the development and preliminary evaluation through focus groups of a novel highly-interactive multimedia-education software program for patients diagnosed with localized prostate cancer. The prostate interactive education system uses the metaphor of rooms in a virtual health center (ie, reception area, a library, physician offices, group meeting room) to organize information. Text information contained in the library is tailored to a person's information-seeking preference (ie, high versus low information seeker). We conducted a preliminary evaluation through 5 separate focus groups with prostate cancer survivors (N = 18) and their spouses (N = 15). Focus group results point to the timeliness and high acceptability of the software among the target audience. Results also underscore the importance of a guide or tutor who assists in navigating the program and who responds to queries to facilitate information retrieval. Focus groups have established the validity of our approach and point to new directions to further enhance the user interface.

Crystallographic analysis of NHERF1–PLCβ3 interaction provides structural basis for CXCR2 signaling in pancreatic cancer

International Nuclear Information System (INIS)

Jiang, Yuanyuan; Wang, Shuo; Holcomb, Joshua; Trescott, Laura; Guan, Xiaoqing; Hou, Yuning; Brunzelle, Joseph; Sirinupong, Nualpun; Li, Chunying; Yang, Zhe

2014-01-01

Highlights: • CXCR2–NHERF1–PLCβ3 complex regulates CXCR2 signaling in pancreatic cancer. • The crystal structure of the NHERF1 PDZ1 domain in complex with PLCβ3. • The structure reveals specificity determinants of PDZ1–PLCβ3 interaction. • Endogenous PLCβ3 in pancreatic cancer cells interacts with both PDZ1 and PDZ2. • Structural basis of the PDZ1–PLCβ3 interaction is valuable in selective drug design. - Abstract: The formation of CXCR2–NHERF1–PLCβ3 macromolecular complex in pancreatic cancer cells regulates CXCR2 signaling activity and plays an important role in tumor proliferation and invasion. We previously have shown that disruption of the NHERF1-mediated CXCR2–PLCβ3 interaction abolishes the CXCR2 signaling cascade and inhibits pancreatic tumor growth in vitro and in vivo. Here we report the crystal structure of the NHERF1 PDZ1 domain in complex with the C-terminal PLCβ3 sequence. The structure reveals that the PDZ1–PLCβ3 binding specificity is achieved by numerous hydrogen bonds and hydrophobic contacts with the last four PLCβ3 residues contributing to specific interactions. We also show that PLCβ3 can bind both NHERF1 PDZ1 and PDZ2 in pancreatic cancer cells, consistent with the observation that the peptide binding pockets of these PDZ domains are highly structurally conserved. This study provides an understanding of the structural basis for the PDZ-mediated NHERF1–PLCβ3 interaction that could prove valuable in selective drug design against CXCR2-related cancers

Crystallographic analysis of NHERF1–PLCβ3 interaction provides structural basis for CXCR2 signaling in pancreatic cancer

Energy Technology Data Exchange (ETDEWEB)

Jiang, Yuanyuan; Wang, Shuo; Holcomb, Joshua; Trescott, Laura; Guan, Xiaoqing; Hou, Yuning [Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, MI (United States); Brunzelle, Joseph [Advanced Photon Source, Argonne National Lab, Argonne, IL (United States); Sirinupong, Nualpun [Nutraceuticals and Functional Food Research and Development Center, Prince of Songkla University, Hat-Yai, Songkhla (Thailand); Li, Chunying, E-mail: cl@med.wayne.edu [Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, MI (United States); Yang, Zhe, E-mail: zyang@med.wayne.edu [Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, MI (United States)

2014-04-04

Highlights: • CXCR2–NHERF1–PLCβ3 complex regulates CXCR2 signaling in pancreatic cancer. • The crystal structure of the NHERF1 PDZ1 domain in complex with PLCβ3. • The structure reveals specificity determinants of PDZ1–PLCβ3 interaction. • Endogenous PLCβ3 in pancreatic cancer cells interacts with both PDZ1 and PDZ2. • Structural basis of the PDZ1–PLCβ3 interaction is valuable in selective drug design. - Abstract: The formation of CXCR2–NHERF1–PLCβ3 macromolecular complex in pancreatic cancer cells regulates CXCR2 signaling activity and plays an important role in tumor proliferation and invasion. We previously have shown that disruption of the NHERF1-mediated CXCR2–PLCβ3 interaction abolishes the CXCR2 signaling cascade and inhibits pancreatic tumor growth in vitro and in vivo. Here we report the crystal structure of the NHERF1 PDZ1 domain in complex with the C-terminal PLCβ3 sequence. The structure reveals that the PDZ1–PLCβ3 binding specificity is achieved by numerous hydrogen bonds and hydrophobic contacts with the last four PLCβ3 residues contributing to specific interactions. We also show that PLCβ3 can bind both NHERF1 PDZ1 and PDZ2 in pancreatic cancer cells, consistent with the observation that the peptide binding pockets of these PDZ domains are highly structurally conserved. This study provides an understanding of the structural basis for the PDZ-mediated NHERF1–PLCβ3 interaction that could prove valuable in selective drug design against CXCR2-related cancers.

Pleural ultrasound as an adjunct to physical examination in the preoperative evaluation of lung cancer patients.

Science.gov (United States)

Bah, Ismaël; Goudie, Eric; Khereba, Mohamed; Ferraro, Pasquale; Duranceau, André; Martin, Jocelyne; Thiffault, Vicky; Liberman, Moishe

2014-05-01

Preoperative evaluation of patients with suspected or confirmed lung cancer consists of clinical and radiological staging. Malignant pleural effusion is a poor prognosticator in non-small-cell lung cancer. Pleural ultrasound (PU) allows for the assessment of pleural effusion, providing real-time guidance for its aspiration and cytological analysis. Pleural Ultrasonography in Lung Cancer (PULC) as an adjunct to physical examination has the potential to improve preoperative staging of non-small-cell lung cancer during first surgical encounter by allowing the evaluation of previously unassessed pleural effusion. This study consisted of a prospective trial of surgeon-performed PU in the preoperative evaluation of lung cancer patients. All patients evaluated in the thoracic surgery clinic with the new or presumed diagnosis of lung cancer were eligible. A portable ultrasound machine was used to evaluate pleural fluid in the bilateral costophrenic sulci with pleural fluid aspiration for cytological analysis. Forty-five patients were prospectively enrolled over a 3-month period. Thirteen patients had ultrasound evidence of a pleural effusion, of which 3 were significant enough for aspiration. Cytological analysis of these effusions yielded malignant cells in 1 patient. Positive PULC evaluation led to a change in clinical staging (M0 to M1a) in 10 patients and a change in pathological staging (pleural fluid cytology positive) in 1 patient. The time required for PULC examination was 15 ± 7 min. There were no complications related to the procedures. Preoperative pleural ultrasonography is a rapid and effective way to improve precision of staging in patients with lung cancer. More precise staging may allow for more appropriate testing, patient prognostication and operative planning.

HSD3B and gene-gene interactions in a pathway-based analysis of genetic susceptibility to bladder cancer.

Directory of Open Access Journals (Sweden)

Angeline S Andrew

Full Text Available Bladder cancer is the 4(th most common cancer among men in the U.S. We analyzed variant genotypes hypothesized to modify major biological processes involved in bladder carcinogenesis, including hormone regulation, apoptosis, DNA repair, immune surveillance, metabolism, proliferation, and telomere maintenance. Logistic regression was used to assess the relationship between genetic variation affecting these processes and susceptibility in 563 genotyped urothelial cell carcinoma cases and 863 controls enrolled in a case-control study of incident bladder cancer conducted in New Hampshire, U.S. We evaluated gene-gene interactions using Multifactor Dimensionality Reduction (MDR and Statistical Epistasis Network analysis. The 3'UTR flanking variant form of the hormone regulation gene HSD3B2 was associated with increased bladder cancer risk in the New Hampshire population (adjusted OR 1.85 95%CI 1.31-2.62. This finding was successfully replicated in the Texas Bladder Cancer Study with 957 controls, 497 cases (adjusted OR 3.66 95%CI 1.06-12.63. The effect of this prevalent SNP was stronger among males (OR 2.13 95%CI 1.40-3.25 than females (OR 1.56 95%CI 0.83-2.95, (SNP-gender interaction P = 0.048. We also identified a SNP-SNP interaction between T-cell activation related genes GATA3 and CD81 (interaction P = 0.0003. The fact that bladder cancer incidence is 3-4 times higher in males suggests the involvement of hormone levels. This biologic process-based analysis suggests candidate susceptibility markers and supports the theory that disrupted hormone regulation plays a role in bladder carcinogenesis.

Prostate cancer risk locus at 8q24 as a regulatory hub by physical interactions with multiple genomic loci across the genome.

Science.gov (United States)

Du, Meijun; Yuan, Tiezheng; Schilter, Kala F; Dittmar, Rachel L; Mackinnon, Alexander; Huang, Xiaoyi; Tschannen, Michael; Worthey, Elizabeth; Jacob, Howard; Xia, Shu; Gao, Jianzhong; Tillmans, Lori; Lu, Yan; Liu, Pengyuan; Thibodeau, Stephen N; Wang, Liang

2015-01-01

Chromosome 8q24 locus contains regulatory variants that modulate genetic risk to various cancers including prostate cancer (PC). However, the biological mechanism underlying this regulation is not well understood. Here, we developed a chromosome conformation capture (3C)-based multi-target sequencing technology and systematically examined three PC risk regions at the 8q24 locus and their potential regulatory targets across human genome in six cell lines. We observed frequent physical contacts of this risk locus with multiple genomic regions, in particular, inter-chromosomal interaction with CD96 at 3q13 and intra-chromosomal interaction with MYC at 8q24. We identified at least five interaction hot spots within the predicted functional regulatory elements at the 8q24 risk locus. We also found intra-chromosomal interaction genes PVT1, FAM84B and GSDMC and inter-chromosomal interaction gene CXorf36 in most of the six cell lines. Other gene regions appeared to be cell line-specific, such as RRP12 in LNCaP, USP14 in DU-145 and SMIN3 in lymphoblastoid cell line. We further found that the 8q24 functional domains more likely interacted with genomic regions containing genes enriched in critical pathways such as Wnt signaling and promoter motifs such as E2F1 and TCF3. This result suggests that the risk locus may function as a regulatory hub by physical interactions with multiple genes important for prostate carcinogenesis. Further understanding genetic effect and biological mechanism of these chromatin interactions will shed light on the newly discovered regulatory role of the risk locus in PC etiology and progression. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Molecular basis for the interplay of apoptosis and proliferation mediated by Bcl-xL:Bim interactions in pancreatic cancer cells

International Nuclear Information System (INIS)

Abrol, Ravinder; Edderkaoui, Mouad; Goddard, William A.; Pandol, Stephen J.

2012-01-01

Highlights: ► Direct role of Bcl-2 protein interactions in cell proliferation is not clear. ► Designed Bcl-xL mutants show opposite effects on apoptosis and proliferation. ► Disrupting Bcl-xL:Bim interaction increased apoptosis in pancreatic cancer. ► Disrupting Bcl-xL:Bim interaction decreased proliferation in pancreatic cancer. ► Bcl-xL:Bim interaction can control both apoptosis and proliferation. -- Abstract: A major mechanism through which cancer cells avoid apoptosis is by promoting the association of anti-apoptotic members of the pro-survival Bcl-2 protein family (like Bcl-2 and Bcl-xL) with BH 3 domain-only proteins (like Bim and Bid). Apoptosis and cell proliferation have been shown to be linked for many cancers but the molecular basis for this link is far from understood. We have identified the Bcl-xL:Bim protein–protein interface as a direct regulator of proliferation and apoptosis in pancreatic cancer cells. We were able to predict and subsequently verify experimentally the effect of various Bcl-xL single-point mutants (at the position A142) on binding to Bim by structural analysis and computational modeling of the inter-residue interactions at the Bcl-xL:Bim protein–protein interface. The mutants A142N, A142Q, and A142Y decreased binding of Bim to Bcl-xL and A142S increased this binding. The Bcl-xL mutants, with decreased affinity for Bim, caused an increase in apoptosis and a corresponding decrease in cell proliferation. However, we could prevent these effects by introducing a small interfering RNA (siRNA) targeted at Bim. These results show a novel role played by the Bcl-xL:Bim interaction in regulating proliferation of pancreatic cancer cells at the expense of apoptosis. This study presents a physiologically relevant model of the Bcl-xL:Bim interface that can be used for rational therapeutic design for the inhibition of proliferation and cancer cell resistance to apoptosis.

Mortality from breast cancer after irradiation during fluoroscopic examinations in patients being treated for tuberculosis

International Nuclear Information System (INIS)

Miller, A.B.; Howe, G.R.; Sherman, G.J.; Lindsay, J.P.; Yaffe, M.J.; Dinner, P.J.; Risch, H.A.; Preston, D.L.

1989-01-01

The increasing use of mammography to screen asymptomatic women makes it important to know the risk of breast cancer associated with exposure to low levels of ionizing radiation. We examined the mortality from breast cancer in a cohort of 31,710 women who had been treated for tuberculosis at Canadian sanatoriums between 1930 and 1952. A substantial proportion (26.4 percent) had received radiation doses to the breast of 10 cGy or more from repeated fluoroscopic examinations during therapeutic pneumothoraxes. Women exposed to greater than or equal to 10 cGy of radiation had a relative risk of death from breast cancer of 1.36, as compared with those exposed to less than 10 cGy (95 percent confidence interval, 1.11 to 1.67; P = 0.001). The data were most consistent with a linear dose-response relation. The risk was greatest among women who had been exposed to radiation when they were between 10 and 14 years of age; they had a relative risk of 4.5 per gray, and an additive risk of 6.1 per 10(4) person-years per gray. With increasing age at first exposure, there was substantially less excess risk, and the radiation effect appeared to peak approximately 25 to 34 years after the first exposure. Our additive model for lifetime risk predicts that exposure to 1 cGy at the age of 40 increases the number of deaths from breast cancer by 42 per million women. We conclude that the risk of breast cancer associated with radiation decreases sharply with increasing age at exposure and that even a small benefit to women of screening mammography would outweigh any possible risk of radiation-induced breast cancer

An examination of social interaction profiles based on the factors measured by the screen for social interaction.

Science.gov (United States)

Mahoney, Emery B; Breitborde, Nicholas J K; Leone, Sarah L; Ghuman, Jaswinder Kaur

2014-10-01

Deficits in the capacity to engage in social interactions are a core deficit associated with Autistic Disorder (AD) and Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS). These deficits emerge at a young age, making screening for social interaction deficits and interventions targeted at improving capacity in this area important for early identification and intervention. Screening and early intervention efforts are particularly important given the poor short and long term outcomes for children with Autism Spectrum Disorders (ASDs) who experience social interaction deficits. The Screen for Social Interaction (SSI) is a well-validated screening measure that examines a child's capacity for social interaction using a developmental approach. The present study identified four underlying factors measured by the SSI, namely, Connection with Caregiver, Interaction/Imagination, Social Approach/Interest, and Agreeable Nature. The resulting factors were utilized to compare social interaction profiles across groups of children with AD, PDD-NOS, children with non-ASD developmental and/or psychiatric conditions and typically developing children. The results indicate that children with AD and those with PDD-NOS had similar social interaction profiles, but were able to be distinguished from typically developing children on every factor and were able to be distinguished from children with non-ASD psychiatric conditions on every factor except the Connection with Caregiver factor. In addition, children with non-ASD developmental and/or psychiatric conditions could be distinguished from typically developing children on the Connection with Caregiver factor and the Social Approach/Interest factor. These findings have implications for screening and intervention for children with ASDs and non-ASD psychiatric conditions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Evaluating an Interactive, Multimedia Education and Decision Program for Early-Stage Prostate Cancer Patients in a Randomized Controlled Trial

National Research Council Canada - National Science Library

Diefenbach, Michael A

2005-01-01

...). To educate patients about prostate cancer and its treatment and to ease their decisional burden, we have developed an innovative CD-ROM based multimedia prostate cancer interactive education system...

Genetic variants and traits related to insulin-like growth factor-I and insulin resistance and their interaction with lifestyles on postmenopausal colorectal cancer risk.

Directory of Open Access Journals (Sweden)

Su Yon Jung

Full Text Available Genetic variants and traits in metabolic signaling pathways may interact with lifestyle factors such as obesity, physical activity, and exogenous estrogen (E, influencing postmenopausal colorectal cancer (CRC risk, but these interrelated pathways are not fully understood. In this case-cohort study, we examined 33 single-nucleotide polymorphisms (SNPs in genes related to insulin-like growth factor-I (IGF-I/ insulin resistance (IR traits and signaling pathways, using data from 704 postmenopausal women in Women's Health Initiative Observation ancillary studies. Stratifying by the lifestyle modifiers, we assessed the effects of IGF-I/IR traits (fasting total and free IGF-I, IGF binding protein-3, insulin, glucose, and homeostatic model assessment-insulin resistance on CRC risk as a mediator or influencing factor. Six SNPs in the INS, IGF-I, and IGFBP3 genes were associated with CRC risk, and those associations differed between non-obese/active and obese/inactive women and between E nonusers and users. Roughly 30% of the cancer risk due to the SNP was mediated by IGF-I/IR traits. Likewise, carriers of 11 SNPs in the IRS1 and AKT1/2 genes (signaling pathway-related genetic variants had different associations with CRC risk between strata, and the proportion of the SNP-cancer association explained by traits varied from 30% to 50%. Our findings suggest that IGF-I/IR genetic variants interact with obesity, physical activity, and exogenous E, altering postmenopausal CRC risk, through IGF-I/IR traits, but also through different pathways. Unraveling gene-phenotype-lifestyle interactions will provide data on potential genetic targets in clinical trials for cancer prevention and intervention strategies to reduce CRC risk.

Dissecting Tumor-Stromal Interactions in Breast Cancer Bone Metastasis

Directory of Open Access Journals (Sweden)

Yibin Kang

2016-06-01

Full Text Available Bone metastasis is a frequent occurrence in breast cancer, affecting more than 70% of late stage cancer patients with severe complications such as fracture, bone pain, and hypercalcemia. The pathogenesis of osteolytic bone metastasis depends on cross-communications between tumor cells and various stromal cells residing in the bone microenvironment. Several growth factor signaling pathways, secreted micro RNAs (miRNAs and exosomes are functional mediators of tumor-stromal interactions in bone metastasis. We developed a functional genomic approach to systemically identified molecular pathways utilized by breast cancer cells to engage the bone stroma in order to generate osteolytic bone metastasis. We showed that elevated expression of vascular cell adhesion molecule 1 (VCAM1 in disseminated breast tumor cells mediates the recruitment of pre-osteoclasts and promotes their differentiation to mature osteoclasts during the bone metastasis formation. Transforming growth factor β (TGF-β is released from bone matrix upon bone destruction, and signals to breast cancer to further enhance their malignancy in developing bone metastasis. We furthered identified Jagged1 as a TGF-β target genes in tumor cells that engaged bone stromal cells through the activation of Notch signaling to provide a positive feedback to promote tumor growth and to activate osteoclast differentiation. Substantially change in miRNA expression was observed in osteoclasts during their differentiation and maturation, which can be exploited as circulating biomarkers of emerging bone metastasis and therapeutic targets for the treatment of bone metastasis. Further research in this direction may lead to improved diagnosis and treatment strategies for bone metastasis.

Identification of new genetic susceptibility loci for breast cancer through consideration of gene-environment interactions

DEFF Research Database (Denmark)

Schoeps, Anja; Rudolph, Anja; Seibold, Petra

2014-01-01

recently proposed hybrid methods and a joint test of association and interaction. Analyses were adjusted for age, study, population stratification, and confounding factors as applicable. Three SNPs in two independent loci showed statistically significant association: SNPs rs10483028 and rs2242714......,475 cases and 34,786 controls of European ancestry from up to 23 studies in the Breast Cancer Association Consortium were included. Overall, 71,527 single nucleotide polymorphisms (SNPs), enriched for association with breast cancer, were tested for interaction with 10 environmental risk factors using three...... in perfect linkage disequilibrium on chromosome 21 and rs12197388 in ARID1B on chromosome 6. While rs12197388 was identified using the joint test with parity and with age at menarche (P-values = 3 × 10(-07)), the variants on chromosome 21 q22.12, which showed interaction with adult body mass index (BMI) in 8...

Methylenetetrahydrofolate reductase polymorphisms and interaction with smoking and alcohol consumption in lung cancer risk: a case-control study in a Japanese population

Directory of Open Access Journals (Sweden)

Takayama Koichi

2011-10-01

Full Text Available Abstract Background Cigarette smoking is an established risk factor of lung cancer development while the current epidemiological evidence is suggestive of an increased lung cancer risk associated with alcohol consumption. Dietary folate, which is present in a wide range of fresh fruits and vegetables, may be a micronutrient that has a beneficial impact on lung carcinogenesis. Methylenetetrahydrofolate reductase (MTHFR plays a crucial role in regulating folate metabolism, which affects both DNA synthesis/repair and methylation. We examined if smoking or alcohol consumption modify associations between MTHFR polymorphisms and lung cancer risk. Methods We evaluated the role of the MTHFR C677T (rs1801133 and A1298C (rs1801131 polymorphisms in a case-control study comprised of 462 lung cancer cases and 379 controls in a Japanese population. Logistic regression was used to assess the adjusted odds ratios (OR and 95% confidence intervals (95% CI. Results The TT genotype of the C677T polymorphism was significantly associated with an increased risk of lung cancer (OR = 2.27, 95% CI = 1.42 - 3.62, P Conclusions The C677T polymorphism was significantly associated with lung cancer risk. Although the A1298C polymorphism was not associated with lung cancer risk, a significant interaction with drinking was observed. Future studies incorporating data on folate intake may undoubtedly lead to a more thorough understanding of the role of the MTHFR polymorphisms in lung cancer development.

Obesity and Cancer Metabolism: A Perspective on Interacting Tumor-Intrinsic and Extrinsic Factors.

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Doerstling, Steven S; O'Flanagan, Ciara H; Hursting, Stephen D

2017-01-01

Obesity is associated with increased risk and poor prognosis of many types of cancers. Several obesity-related host factors involved in systemic metabolism can influence tumor initiation, progression, and/or response to therapy, and these have been implicated as key contributors to the complex effects of obesity on cancer incidence and outcomes. Such host factors include systemic metabolic regulators including insulin, insulin-like growth factor 1, adipokines, inflammation-related molecules, and steroid hormones, as well as the cellular and structural components of the tumor microenvironment, particularly adipose tissue. These secreted and structural host factors are extrinsic to, and interact with, the intrinsic metabolic characteristics of cancer cells to influence their growth and spread. This review will focus on the interplay of these tumor cell-intrinsic and extrinsic factors in the context of energy balance, with the objective of identifying new intervention targets for preventing obesity-associated cancer.

Facading in transcultural interactions: examples from pediatric cancer care in Sweden.

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Pergert, Pernilla

2017-07-01

The aims of the study were to generate a grounded theory explaining the latent pattern of behavior in transcultural care interactions in the context of pediatric cancer care and to unify previously performed studies. The basic tenets of classic grounded theory were applied on a theoretical sample of data from previous studies that included 5 focus group interviews with health care professionals (n = 35) and individual interviews with nurses (n = 12) and foreign-born parents (n = 11). Facading emerged as the core category and is the act of showing an outer appearance that will influence other people's interpretations. In transcultural interactions, facading might be misinterpreted related to different obstacles. Examples are given of different facades explored in pediatric cancer care including strength facading. Facading is a strategy aiming to protect oneself and others emotionally in care and includes: emotional facading and facading-sensitive issues. This grounded theory could help make health care professionals aware of different meanings of facading across cultures in health care. Also, awareness is needed of different views on emotional facading and facading-sensitive issues to provide a congruent care. Copyright © 2016 John Wiley & Sons, Ltd.

Comparison of 4 established DASH diet indexes: examining associations of index scores and colorectal cancer.

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Miller, Paige E; Cross, Amanda J; Subar, Amy F; Krebs-Smith, Susan M; Park, Yikyung; Powell-Wiley, Tiffany; Hollenbeck, Albert; Reedy, Jill

2013-09-01

Multiple diet indexes have been developed to capture the Dietary Approaches to Stop Hypertension (DASH) dietary pattern and examine relations with health outcomes but have not been compared within the same study population to our knowledge. We compared 4 established DASH indexes and examined associations with colorectal cancer. Scores were generated from a food-frequency questionnaire in the NIH-AARP Diet and Health Study (n = 491,841). Separate indexes defined by Dixon (7 food groups, saturated fat, and alcohol), Mellen (9 nutrients), Fung (7 food groups and sodium), and Günther (8 food groups) were used. HRs and 95% CIs for colorectal cancer were generated by using Cox proportional hazard models. From 1995 through 2006, 6752 incident colorectal cancer cases were ascertained. In men, higher scores were associated with reduced colorectal cancer incidence by comparing highest to lowest quintiles for all indexes as follows: Dixon (HR: 0.77; 95% CI: 0.69, 0.87), Mellen (HR: 0.78; 95% CI: 0.71, 0.86), Fung (HR: 0.75; 95% CI: 0.68, 0.83), and Günther (HR: 0.81; 95% CI: 0.74, 0.90). Higher scores in women were inversely associated with colorectal cancer incidence by using methods defined by Mellen (HR: 0.79; 95% CI: 0.68, 0.91), Fung (HR: 0.84; 95% CI: 0.73, 0.96), and Günther (HR: 0.84; 95% CI: 0.73.0.97) but not Dixon (HR: 1.01; 95% CI: 0.80, 1.28). The consistency in findings, particularly in men, suggests that all indexes capture an underlying construct inherent in the DASH dietary pattern, although the specific index used can affect results.

Examining applying high performance genetic data feature selection and classification algorithms for colon cancer diagnosis.

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Al-Rajab, Murad; Lu, Joan; Xu, Qiang

2017-07-01

This paper examines the accuracy and efficiency (time complexity) of high performance genetic data feature selection and classification algorithms for colon cancer diagnosis. The need for this research derives from the urgent and increasing need for accurate and efficient algorithms. Colon cancer is a leading cause of death worldwide, hence it is vitally important for the cancer tissues to be expertly identified and classified in a rapid and timely manner, to assure both a fast detection of the disease and to expedite the drug discovery process. In this research, a three-phase approach was proposed and implemented: Phases One and Two examined the feature selection algorithms and classification algorithms employed separately, and Phase Three examined the performance of the combination of these. It was found from Phase One that the Particle Swarm Optimization (PSO) algorithm performed best with the colon dataset as a feature selection (29 genes selected) and from Phase Two that the Support Vector Machine (SVM) algorithm outperformed other classifications, with an accuracy of almost 86%. It was also found from Phase Three that the combined use of PSO and SVM surpassed other algorithms in accuracy and performance, and was faster in terms of time analysis (94%). It is concluded that applying feature selection algorithms prior to classification algorithms results in better accuracy than when the latter are applied alone. This conclusion is important and significant to industry and society. Copyright © 2017 Elsevier B.V. All rights reserved.

Quantitative Chemical-Genetic Interaction Map Connects Gene Alterations to Drug Responses | Office of Cancer Genomics

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In a recent Cancer Discovery report, CTD2 researchers at the University of California in San Francisco developed a new quantitative chemical-genetic interaction mapping approach to evaluate drug sensitivity or resistance in isogenic cell lines. Performing a high-throughput screen with isogenic cell lines allowed the researchers to explore the impact of a panel of emerging and established drugs on cells overexpressing a single cancer-associated gene in isolation.

Cancer risk assessment of patients undergoing computed tomography examination at the Korle-Bu Teaching Hospital (KBTH)

International Nuclear Information System (INIS)

Sackey, T.A.

2015-07-01

The aim of this study is to estimate the effective dose and assess the lifetime attributable risk of cancer incidence of patients undergoing computed tomography scan at the korle-bu Teaching Hospital. Data on volume CT dose index (CTDI vol) and dose length product (DLP ) displayed on the scanner control console was recorded after confirmation of the results by performing independent checks on a phantom. The effective doses were estimated using the displayed and the anatomic region specific conversion factors (K ). The average effective dose for the head, abdomen, chest, neck, and pelvis were 3.63± 2.39mSv, 15.37±8.49 mSv, 12.72 ± 13.97 mSv, 4.04 ± 1.47 mSv and 15.8 ± 3.59 mSv respectively. Effective doses for the head and neck were within the typical range of (1-10mSv) for CT examinations whilst abdomen, chest and pelvis were above 10mSv. The average life attributable risk of cancer incidence for each region of examination were determined from the effective dose, sex and age using the model proposed in BEIR VII report . The average cancer risk incidence for head, neck, chest, abdomen and pelvis examinations were low in the range 1 in 10,000 to 1 in 1,000. There were wide variations in the effective dose values obtained for the same region under examination. This trend calls for the optimization of CT examination protocols to be established to ensure that patient doses are as low as reasonably achievable, economic and social factors being taken into account. (author)

Estimation of organ doses and risk of cancer associated with CT examination

International Nuclear Information System (INIS)

Ahmed, Nagla Nooraldaim

2017-11-01

The purpose of this study to estimate the organ closes and risk of cancer associated with CT examinations in Khartoum state, where the study conducted in three hospitals; Alzytouna , royal scan and Royal Care. From April to November 2017, and the data collected from 120 patients, 40 patents from each hospital undergoing CT brain and abdomen examinations. The data were entered to CT - Expo version 2.4 software for calculation the effective dose and organ dose and by Xray risk web site for calculate the risk factor associated with CT examinations. Results have shown the values of effective dose that found 9.73 mSv for all patients and for female and male 9.9 mSv respectively. The effective dose from Brain examinations in three hospitals Alzytouna Royal scan and Royal Care was 16.9 mSv, 3.7 mSv, 3.8 mSv respectively, and from abdomen examinations was 4.2 mSv, 7.6 mSv, 22.2 mSv respectively. Comparing te effective dose from the hospitals, for Ct. Brain in Alzytouna hospital was higher than other hospitals; and for CT Abdomen in Royal Care hospital was higher than other hospitals, but still under the risk levels according to the ICRP report. For organ doses results, the most organs exposed from CT. brain was brain, salivary gland, thyroid gland, Bone marrow, Bone surface, Extra thoracic tissue, Eye lens and oral mucosa received ( 70,2, 66.4,15.04, 10.9, 24.9, 14.8,89.5,65.07) mSv respectively. The most organs exposed from CT. Abdomen were liver, stomach, low, Large intestine, Bladder, Bone surface, upper , Large intestine, spleen, kidney, small intestine and prostate received (16.53, 12.8, 33.43, 41.01,20.5, 38.4, 14.7, 28.9, 37.5,30.5 ) mSv respectively. This study found that te ability of cancer induced i the female was higher from the male; dut to body component of the female. (Author)

Gelsolin-Cu/ZnSOD interaction alters intracellular reactive oxygen species levels to promote cancer cell invasion

KAUST Repository

Tochhawng, Lalchhandami

2016-07-07

The actin-binding protein, gelsolin, is a well known regulator of cancer cell invasion. However, the mechanisms by which gelsolin promotes invasion are not well established. As reactive oxygen species (ROS) have been shown to promote cancer cell invasion, we investigated on the hypothesis that gelsolin-induced changes in ROS levels may mediate the invasive capacity of colon cancer cells. Herein, we show that increased gelsolin enhances the invasive capacity of colon cancer cells, and this is mediated via gelsolin\\'s effects in elevating intracellular superoxide (O2 .-) levels. We also provide evidence for a novel physical interaction between gelsolin and Cu/ZnSOD, that inhibits the enzymatic activity of Cu/ZnSOD, thereby resulting in a sustained elevation of intracellular O2 .-. Using microarray data of human colorectal cancer tissues from Gene Omnibus, we found that gelsolin gene expression positively correlates with urokinase plasminogen activator (uPA), an important matrix-degrading protease invovled in cancer invasion. Consistent with the in vivo evidence, we show that increased levels of O2 .- induced by gelsolin overexpression triggers the secretion of uPA. We further observed reduction in invasion and intracellular O2 .- levels in colon cancer cells, as a consequence of gelsolin knockdown using two different siRNAs. In these cells, concurrent repression of Cu/ ZnSOD restored intracellular O2 .- levels and rescued invasive capacity. Our study therefore identified gelsolin as a novel regulator of intracellular O2 .- in cancer cells via interacting with Cu/ZnSOD and inhibiting its enzymatic activity. Taken together, these findings provide insight into a novel function of gelsolin in promoting tumor invasion by directly impacting the cellular redox milieu.

Examining the Interaction of Taxi and Subway Ridership for Sustainable Urbanization

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Miaoyi Li

2017-02-01

Full Text Available A transit ridership study is an essential part of sustainability, and can provide a deep understanding of people’s travel patterns for efficient transportation development and urbanization. However, there is a lack of empirical studies comparing subway and taxi services, and their interactions within a city, that is to say, the interdependent transportation networks. Incorporating new data, this study aims to examine the spatial variation of urban taxi ridership due to the impacts of a new subway line operation opened in 2014 in Wuxi, China. We examine the spatial patterns and interactions of ridership in Wuxi by integrating taxi trajectory from GPS data and subway data from continuously collected fare transactions. The results indicated that the demand for taxi and subway usage is quite elastic with respect to both location and time, and the new subway’s opening had more influence on areas adjacent to subway stations and urban center-suburban travel. Furthermore, increases in travel time and distance would increase the demand for subway, while taxi trips largely represented movements for those locations that the subway could not reach. This paper betters the understanding of travel patterns through large volumes of transportation data for sustainable urbanization policy design.

Molecular basis for the interplay of apoptosis and proliferation mediated by Bcl-xL:Bim interactions in pancreatic cancer cells

Energy Technology Data Exchange (ETDEWEB)

Abrol, Ravinder, E-mail: abrol@wag.caltech.edu [Materials and Process Simulation Center, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125 (United States); Edderkaoui, Mouad [Veterans Affairs Greater Los Angeles Healthcare System and UCLA, Los Angeles, CA 90073 (United States); Goddard, William A. [Materials and Process Simulation Center, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125 (United States); Pandol, Stephen J., E-mail: stephen.pandol@va.gov [Veterans Affairs Greater Los Angeles Healthcare System and UCLA, Los Angeles, CA 90073 (United States)

2012-06-15

Highlights: Black-Right-Pointing-Pointer Direct role of Bcl-2 protein interactions in cell proliferation is not clear. Black-Right-Pointing-Pointer Designed Bcl-xL mutants show opposite effects on apoptosis and proliferation. Black-Right-Pointing-Pointer Disrupting Bcl-xL:Bim interaction increased apoptosis in pancreatic cancer. Black-Right-Pointing-Pointer Disrupting Bcl-xL:Bim interaction decreased proliferation in pancreatic cancer. Black-Right-Pointing-Pointer Bcl-xL:Bim interaction can control both apoptosis and proliferation. -- Abstract: A major mechanism through which cancer cells avoid apoptosis is by promoting the association of anti-apoptotic members of the pro-survival Bcl-2 protein family (like Bcl-2 and Bcl-xL) with BH{sub 3} domain-only proteins (like Bim and Bid). Apoptosis and cell proliferation have been shown to be linked for many cancers but the molecular basis for this link is far from understood. We have identified the Bcl-xL:Bim protein-protein interface as a direct regulator of proliferation and apoptosis in pancreatic cancer cells. We were able to predict and subsequently verify experimentally the effect of various Bcl-xL single-point mutants (at the position A142) on binding to Bim by structural analysis and computational modeling of the inter-residue interactions at the Bcl-xL:Bim protein-protein interface. The mutants A142N, A142Q, and A142Y decreased binding of Bim to Bcl-xL and A142S increased this binding. The Bcl-xL mutants, with decreased affinity for Bim, caused an increase in apoptosis and a corresponding decrease in cell proliferation. However, we could prevent these effects by introducing a small interfering RNA (siRNA) targeted at Bim. These results show a novel role played by the Bcl-xL:Bim interaction in regulating proliferation of pancreatic cancer cells at the expense of apoptosis. This study presents a physiologically relevant model of the Bcl-xL:Bim interface that can be used for rational therapeutic design for the

An epidemiological analysis of potential associations between C-reactive protein, inflammation, and prostate cancer in the male US population using the 2009 - 2010 National Health and Nutrition Examination Survey (NHANES) data

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St. Hill, Catherine; Lutfiyya, M. Nawal

2015-08-01

Prostate cancer is the second leading cause of cancer-related deaths in US males, yet much remains to be learned about the role of inflammation in its etiology. We hypothesized that preexisting exposure to chronic inflammatory conditions caused by infectious agents or inflammatory diseases increase the risk of prostate cancer. Using the 2009-2010 National Health and Nutrition Examination Survey, we examined the relationships between demographic variables, inflammation, infection, circulating plasma C-reactive protein (CRP), and the risk of occurrence of prostate cancer in US men over 18 years of age. Using IBM SPSS, we performed bivariate and logistic regression analyses using high CRP values as the dependent variable and five study covariates including prostate cancer status. From 2009 - 2010, an estimated 5,448,373 men reported having prostate cancer of which the majority were Caucasian (70.1%) and were aged 40 years and older (62.7%). Bivariate analyses demonstrated that high CRP was not associated with an increased risk of prostate cancer. Greater odds of having prostate cancer were revealed for men that had inflammation related to disease (OR = 1.029, CI 1.029-1.029) and those who were not taking drugs to control inflammation (OR = 1.330, CI 1.324-1.336). Men who did not have inflammation resulting from non-infectious diseases had greater odds of not having prostate cancer (OR = 1.031, CI 1.030-1.031). Logistic regression analysis yielded that men with the highest CRP values had greater odds of having higher household incomes and lower odds of having received higher education, being aged 40 years or older, being of a race or ethnicity different from other, and of having prostate cancer. Our results show that chronic inflammation of multiple etiologies is a risk factor for prostate cancer and that CRP is not associated with this increased risk. Further research is needed to elucidate the complex interactions between inflammation and prostate cancer.

Muscle invasive bladder cancer: examining survivor burden and unmet needs.

Science.gov (United States)

Mohamed, Nihal E; Chaoprang Herrera, Phapichaya; Hudson, Shawna; Revenson, Tracey A; Lee, Cheryl T; Quale, Diane Z; Zarcadoolas, Christina; Hall, Simon J; Diefenbach, Michael A

2014-01-01

Although improvements in perioperative care have decreased surgical morbidity after radical cystectomy for muscle invasive bladder cancer, treatment side effects still have a negative impact on patient quality of life. We examined unmet patient needs along the illness trajectory. A total of 30 patients (26.7% women) treated with cystectomy and urinary diversion for muscle invasive bladder cancer participated in the study. Patients were recruited from the Department of Urology at Mount Sinai and through advertisements on the Bladder Cancer Advocacy Network (BCAN) website between December 2011 and September 2012. Data were collected at individual interviews, which were audiotaped and transcribed. Transcribed data were quantitatively analyzed to explore key unmet needs. At diagnosis unmet informational needs were predominant, consisting of insufficient discussion of certain topics, including urinary diversion options and their side effects, self-care, the recovery process and medical insurance. Unmet psychological needs related to depression, and worries about changes in body image and sexual function were reported. Postoperative unmet needs revolved around medical needs (eg pain and bowel dysfunction) and instrumental needs (eg need of support for stomal appliances, catheters and incontinence). During survivorship (ie 6 to 72 months postoperatively) unmet needs centered around psychological support (ie depression, poor body image and sexual dysfunction) and instrumental support (eg difficulty adjusting to changes in daily living). Meeting patient needs is imperative to ensure adequate patient involvement in health care and enhance postoperative quality of life. An effective support provision plan should follow changes in patient needs. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

The effects of Internet or interactive computer-based patient education in the field of breast cancer: a systematic literature review.

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Ryhänen, Anne M; Siekkinen, Mervi; Rankinen, Sirkku; Korvenranta, Heikki; Leino-Kilpi, Helena

2010-04-01

The aim of this systematic review was to analyze what kind of Internet or interactive computer-based patient education programs have been developed and to analyze the effectiveness of these programs in the field of breast cancer patient education. Patient education for breast cancer patients is an important intervention to empower the patient. However, we know very little about the effects and potential of Internet-based patient education in the empowerment of breast cancer patients. Complete databases were searched covering the period from the beginning of each database to November 2008. Studies were included if they concerned patient education for breast cancer patients with Internet or interactive computer programs and were based on randomized controlled, on clinical trials or quasi-experimental studies. We identified 14 articles involving 2374 participants. The design was randomized controlled trial in nine papers, in two papers clinical trial and in three quasi-experimental. Seven of the studies were randomized to experimental and control groups, in two papers participants were grouped by ethnic and racial differences and by mode of Internet use and three studies measured the same group pre- and post-tests after using a computer program. The interventions used were described as interactive computer or multimedia programs and use of the Internet. The methodological solutions of the studies varied. The effects of the studies were diverse except for knowledge-related issues. Internet or interactive computer-based patient education programs in the care of breast cancer patients may have positive effect increasing breast cancer knowledge. The results suggest a positive relationship between the Internet or computer-based patient education program use and the knowledge level of patients with breast cancer but a diverse relationship between patient's participation and other outcome measures. There is need to develop and research more Internet-based patient education

Coping with Early Stage Breast Cancer:Examining the Influence of Personality Traits and Interpersonal Closeness

Directory of Open Access Journals (Sweden)

Emanuela eSaita

2015-02-01

Full Text Available The study examines the influence of personality traits and close relationships on the coping style of women with breast cancer. A sample of seventy-two Italian patients receiving treatment for early stage breast cancer was recruited. Participants completed questionnaires measuring personality traits (Interpersonal Adaptation Questionnaire, interpersonal closeness (Inclusion of the Other in the Self Scale, and adjustment to cancer (Mini-Mental Adjustment to Cancer Scale. We hypothesized that diverse personality traits and degrees of closeness contribute to determine the coping styles shown by participants. Multiple regression analyses were conducted for each of the five coping styles (Helplessness/Hopelessness, Anxious Preoccupation, Avoidance, Fatalism, and Fighting Spirit using personality traits and interpersonal closeness variables (Strength of Support Relations, and Number of Support Relations as predictors. Women who rated high on assertiveness and social anxiety were more likely to utilize active coping strategies (Fighting Spirit. Perceived strength of relationships was predictive of using an active coping style while the number of supportive relationships did not correlate with any of the coping styles. Implications for assessment of breast cancer patients at risk for negative adaptation to the illness and the development of psychosocial interventions are discussed.

Jointly they edit: examining the impact of community identification on political interaction in Wikipedia.

Directory of Open Access Journals (Sweden)

Jessica J Neff

Full Text Available BACKGROUND: In their 2005 study, Adamic and Glance coined the memorable phrase 'divided they blog', referring to a trend of cyberbalkanization in the political blogosphere, with liberal and conservative blogs tending to link to other blogs with a similar political slant, and not to one another. As political discussion and activity increasingly moves online, the power of framing political discourses is shifting from mass media to social media. METHODOLOGY/PRINCIPAL FINDINGS: Continued examination of political interactions online is critical, and we extend this line of research by examining the activities of political users within the Wikipedia community. First, we examined how users in Wikipedia choose to display their political affiliation. Next, we analyzed the patterns of cross-party interaction and community participation among those users proclaiming a political affiliation. In contrast to previous analyses of other social media, we did not find strong trends indicating a preference to interact with members of the same political party within the Wikipedia community. CONCLUSIONS/SIGNIFICANCE: Our results indicate that users who proclaim their political affiliation within the community tend to proclaim their identity as a 'Wikipedian' even more loudly. It seems that the shared identity of 'being Wikipedian' may be strong enough to triumph over other potentially divisive facets of personal identity, such as political affiliation.

Jointly They Edit: Examining the Impact of Community Identification on Political Interaction in Wikipedia

Science.gov (United States)

Neff, Jessica J.; Laniado, David; Kappler, Karolin E.; Volkovich, Yana; Aragón, Pablo; Kaltenbrunner, Andreas

2013-01-01

Background In their 2005 study, Adamic and Glance coined the memorable phrase ‘divided they blog’, referring to a trend of cyberbalkanization in the political blogosphere, with liberal and conservative blogs tending to link to other blogs with a similar political slant, and not to one another. As political discussion and activity increasingly moves online, the power of framing political discourses is shifting from mass media to social media. Methodology/Principal Findings Continued examination of political interactions online is critical, and we extend this line of research by examining the activities of political users within the Wikipedia community. First, we examined how users in Wikipedia choose to display their political affiliation. Next, we analyzed the patterns of cross-party interaction and community participation among those users proclaiming a political affiliation. In contrast to previous analyses of other social media, we did not find strong trends indicating a preference to interact with members of the same political party within the Wikipedia community. Conclusions/Significance Our results indicate that users who proclaim their political affiliation within the community tend to proclaim their identity as a ‘Wikipedian’ even more loudly. It seems that the shared identity of ‘being Wikipedian’ may be strong enough to triumph over other potentially divisive facets of personal identity, such as political affiliation. PMID:23573269

A systematic review of dyadic studies examining relationship quality in couples facing colorectal cancer together.

Science.gov (United States)

Kayser, Karen; Acquati, Chiara; Reese, Jennifer Barsky; Mark, Kristen; Wittmann, Daniela; Karam, Eli

2018-01-01

Despite the adverse effects that treatment for colorectal cancer can have on patients' quality of life and, in particular, their intimate relationships, very little research has been conducted on the psychosocial adjustment for both patients and their partners/spouses. The aim of this systematic review was to examine dyadic studies of adjustment in couples in which one partner has been diagnosed with colorectal cancer. Pub Med, PsychINFO, MEDLINE, Social Sciences Abstracts (EBSCO), and the Cochrane Library were systematically searched for studies reporting quality of life outcomes for colorectal cancer patients and their partners/spouses. Only studies that included dyads in the sample were eligible for inclusion. The Quality Assessment Tool for Quantitative Studies was used to evaluate each study. A total of 277 studies were identified, of which 9 studies met the inclusion criteria (N = 388 couples). The methodological quality of the studies was high in that they used standardized instruments validated with their samples, conducted dyadic data analyses (when appropriate), and used longitudinal designs. A synthesis of the studies revealed that (1) relationship factors (eg, support, communication, dyadic coping, and relationship satisfaction) affect adjustment to cancer; (2) cancer-related distress impacts each partner's adjustment or the relationship; and (3) gender, role (patient/caregiver), and clinical characteristics (treatment, mental health) can mediate adjustment to cancer. The quality of the relationship can influence patients' and their partners' adjustment to colorectal cancer. Psychosocial interventions that address relationship issues may be beneficial to couples facing the challenges of colorectal cancer. Copyright © 2016 John Wiley & Sons, Ltd.

Interactive effect of genetic susceptibility with height, body mass index, and hormone replacement therapy on the risk of breast cancer

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Harlid Sophia

2012-06-01

Full Text Available Abstract Background Breast cancer today has many established risk factors, both genetic and environmental, but these risk factors by themselves explain only part of the total cancer incidence. We have investigated potential interactions between certain known genetic and phenotypic risk factors, specifically nine single nucleotide polymorphisms (SNPs and height, body mass index (BMI and hormone replacement therapy (HRT. Methods We analyzed samples from three different study populations: two prospectively followed Swedish cohorts and one Icelandic case–control study. Totally 2884 invasive breast cancer cases and 4508 controls were analysed in the study. Genotypes were determined using Mass spectrometry-Maldi-TOF and phenotypic variables were derived from measurements and/or questionnaires. Odds Ratios and 95% confidence intervals were calculated using unconditional logistic regression with the inclusion of an interaction term in the logistic regression model. Results One SNP (rs851987 in ESR1 tended to interact with height, with an increasingly protective effect of the major allele in taller women (p = 0.007 and rs13281615 (on 8q24 tended to confer risk only in non users of HRT (p-for interaction = 0.03. There were no significant interactions after correction for multiple testing. Conclusions We conclude that much larger sample sets would be necessary to demonstrate interactions between low-risk genetic polymorphisms and the phenotypic variables height, BMI and HRT on the risk for breast cancer. However the present hypothesis-generating study has identified tendencies that would be of interest to evaluate for gene-environment interactions in independent materials.

Recent progress in the development of protein-protein interaction inhibitors targeting androgen receptor-coactivator binding in prostate cancer.

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Biron, Eric; Bédard, François

2016-07-01

The androgen receptor (AR) is a key regulator for the growth, differentiation and survival of prostate cancer cells. Identified as a primary target for the treatment of prostate cancer, many therapeutic strategies have been developed to attenuate AR signaling in prostate cancer cells. While frontline androgen-deprivation therapies targeting either the production or action of androgens usually yield favorable responses in prostate cancer patients, a significant number acquire treatment resistance. Known as the castration-resistant prostate cancer (CRPC), the treatment options are limited for this advanced stage. It has been shown that AR signaling is restored in CRPC due to many aberrant mechanisms such as AR mutations, amplification or expression of constitutively active splice-variants. Coregulator recruitment is a crucial regulatory step in AR signaling and the direct blockade of coactivator binding to AR offers the opportunity to develop therapeutic agents that would remain effective in prostate cancer cells resistant to conventional endocrine therapies. Structural analyses of the AR have identified key surfaces involved in protein-protein interaction with coregulators that have been recently used to design and develop promising AR-coactivator binding inhibitors. In this review we will discuss the design and development of small-molecule inhibitors targeting the AR-coactivator interactions for the treatment of prostate cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.

Interaction of insulin-like growth factor-I and insulin resistance-related genetic variants with lifestyle factors on postmenopausal breast cancer risk.

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Jung, Su Yon; Ho, Gloria; Rohan, Thomas; Strickler, Howard; Bea, Jennifer; Papp, Jeanette; Sobel, Eric; Zhang, Zuo-Feng; Crandall, Carolyn

2017-07-01

Genetic variants and traits in metabolic signaling pathways may interact with obesity, physical activity, and exogenous estrogen (E), influencing postmenopausal breast cancer risk, but these inter-related pathways are incompletely understood. We used 75 single-nucleotide polymorphisms (SNPs) in genes related to insulin-like growth factor-I (IGF-I)/insulin resistance (IR) traits and signaling pathways, and data from 1003 postmenopausal women in Women's Health Initiative Observation ancillary studies. Stratifying via obesity and lifestyle modifiers, we assessed the role of IGF-I/IR traits (fasting IGF-I, IGF-binding protein 3, insulin, glucose, and homeostatic model assessment-insulin resistance) in breast cancer risk as a mediator or influencing factor. Seven SNPs in IGF-I and INS genes were associated with breast cancer risk. These associations differed between non-obese/active and obese/inactive women and between exogenous E non-users and users. The mediation effects of IGF-I/IR traits on the relationship between these SNPs and cancer differed between strata, but only roughly 35% of the cancer risk due to the SNPs was mediated by traits. Similarly, carriers of 20 SNPs in PIK3R1, AKT1/2, and MAPK1 genes (signaling pathways-genetic variants) had different associations with breast cancer between strata, and the proportion of the SNP-cancer relationship explained by traits varied 45-50% between the strata. Our findings suggest that IGF-I/IR genetic variants interact with obesity and lifestyle factors, altering cancer risk partially through pathways other than IGF-I/IR traits. Unraveling gene-phenotype-lifestyle interactions will provide data on potential genetic targets in clinical trials for cancer prevention and intervention strategies to reduce breast cancer risk.

Identification of the Types Properties and Functional Characteristics of Telomerase Expressing Cells in Breast Cancer

National Research Council Canada - National Science Library

Hines, William

2003-01-01

... biochemical and functional properties may be characterized. Through examining the role of telomerase in cancer, this project also fosters the education of the candidate through the interaction with several experts in breast cancer pathology, epidemiology, bio...

The association of physical activity and colorectal and breast cancer: The Fifth Korea National Health and Nutrition Examination Survey (2008-2011).

Science.gov (United States)

Kang, Suh-Jung

2015-06-01

Therapeutic importance of physical activity during and after cancer treatment has been supported. To examine the patterns of physical activity according to the stages of breast and colorectal cancer survivor-ship in Korean, Korean National Health and Nutrition Examination Survey data from 2008 to 2011 were used. International Physical Activity Questionnaire (IPAQ) was utilized to estimate weekly time spent in vigorous- and moderate-intensity physical activity, and walking, and to calculate MET-minute/week. Depending on the survivorship, the subjects were categorized into "never diagnosed with cancer" (group 1), "0-4 yr since cancer diagnosis" (group 2), and "5 or more years since cancer diagnosis" (group 3), separately for colorectal and breast cancer. The associations between physical activity and the cancer survivorship were studied. Following results were obtained: (1) Breast cancer (n=10,167, mean age=48.55±16.27): The mean physical activity levels expressed in MET-minutes/week were 2,064.83, 1748.82, and 1998.36 in groups 1, 2, and 3, respectively. Even though cancer survivors tended to be less active compared to people without cancer, there were no statistically significant difference among the three groups. (2) Colorectal cancer (n=17,270, mean age=48.62): MET-minutes/week was 2064.30, 1084.83, and 709.04 36 in groups 1, 2, and 3, respectively. The differences were significant between group 1 and 2 (F=5.87, P=0.016) and group 1 and 3 (F=28.99, Pphysical activity, colorectal cancer survivors were less active than people without cancer in Korea.

Challenges of Critical Colleagueship: Examining and Reflecting on Mathematics Teacher Study Group Interactions

Science.gov (United States)

Males, Lorraine M.; Otten, Samuel; Herbel-Eisenmann, Beth A.

2010-01-01

This article examines mathematics teacher collegiality by focusing on both the ways in which teachers interacted as critical colleagues in a long-term professional development project and the evolving role of the teacher-educator-researcher as the facilitator of this project. The professional development collaboration comprised two phases: one…

Brain-derived neurotrophic factor (BDNF) -TrKB signaling modulates cancer-endothelial cells interaction and affects the outcomes of triple negative breast cancer.

Science.gov (United States)

Tsai, Yi-Fang; Tseng, Ling-Ming; Hsu, Chih-Yi; Yang, Muh-Hwa; Chiu, Jen-Hwey; Shyr, Yi-Ming

2017-01-01

There is good evidence that the tumor microenvironment plays an important role in cancer metastasis and progression. Our previous studies have shown that brain-derived neurotrophic factor (BDNF) participates in the process of metastasis and in the migration of cancer cells. The aim of this study was to investigate the role of BDNF on the tumor cell microenvironment, namely, the cancer cell-endothelial cell interaction of TNBC cells. We conducted oligoneucleotide microarray analysis of potential biomarkers that are able to differentiate recurrent TNBC from non-recurrent TNBC. The MDA-MB-231 and human endothelial HUVEC lines were used for this study and our approaches included functional studies, such as migration assay, as well as Western blot and real-time PCR analysis of migration and angiogenic signaling. In addition, we analyzed the survival outcome of TNBC breast cancer patients according to their expression level of BDNF using clinical samples. The results demonstrated that BDNF was able to bring about autocrinal (MDA-MB-231) and paracrinal (HUVECs) regulation of BDNF-TrkB gene expression and this affected cell migratory activity. The BDNF-induced migratory activity was blocked by inhibitors of ERK, PI3K and TrkB when MDA-MB-231 cells were examined, but only an inhibitor of ERK blocked this activity when HUVEC cells were used. Furthermore, decreased migratory activity was found for △BDNF and △TrkB cell lines. Ingenuity pathway analysis (IPA) of MDA-MB-231 cells showed that BDNF is a key factor that is able to regulate a network made up of metalloproteases and calmodulin. Protein expression levels in a tissue array of tumor slices were found to be correlated with patient prognosis and the results showed that there was significant correlation of TrkB expression, but not of BDNF. expressionwith patient DFS and OS. Our study demonstrates that up-regulation of the BDNF signaling pathway seems tobe involved in the mechanism associated with early recurrence in

Depressed immune surveillance against cancer: role of deficient T cell: extracellular matrix interactions.

Science.gov (United States)

Górski, A; Castronovo, V; Stepień-Sopniewska, B; Grieb, P; Ryba, M; Mrowiec, T; Korczak-Kowalska, G; Wierzbicki, P; Matysiak, W; Dybowska, B

1994-07-01

Although T cells infiltrate malignant tumors, the local immune response is usually inefficient and tumors escape destruction. While extracellular matrix proteins strongly costimulate T cell responses in normal individuals, our studies indicate that peripheral blood T cells from cancer patients and tumor infiltrating cells respond poorly or are resistant to stimulative signals mediated by collagen I and IV and fibronectin. Moreover, the adhesive properties of cancer T cells are markedly depressed. Those functional deficiencies are paralleled by variable deficits in integrin and non-integrin T cell receptors for extracellular matrix. Immunotherapy with BCG causes a dramatic but transient increase in T cell: ECM interactions.

Impact of Maspin Polymorphism rs2289520 G/C and Its Interaction with Gene to Gene, Alcohol Consumption Increase Susceptibility to Oral Cancer Occurrence.

Science.gov (United States)

Yang, Po-Yu; Miao, Nae-Fang; Lin, Chiao-Wen; Chou, Ying-Erh; Yang, Shun-Fa; Huang, Hui-Chuan; Chang, Hsiu-Ju; Tsai, Hsiu-Ting

2016-01-01

The purpose of this study was to identify gene polymorphisms of mammary serine protease inhibitor (Maspin) specific to patients with oral cancer susceptibility and clinicopathological status. Three single-nucleotide polymorphisms (SNPs) of the Maspin gene from 741 patients with oral cancer and 601 non-cancer controls were analyzed by real-time PCR. The participants with G/G homozygotes or with G/C heterozygotes of Maspin rs2289520 polymorphism had a 2.07-fold (p = 0.01) and a 2.01-fold (p = 0.02) risk of developing oral cancer compared to those with C/C homozygotes. Moreover, gene-gene interaction increased the risk of oral cancer susceptibility among subjects expose to oral cancer related risk factors, including areca, alcohol, and tobacco consumption. G allele of Maspin rs2289520 polymorphism may be a factor that increases the susceptibility to oral cancer. The interactions of gene to oral cancer-related environmental risk factors have a synergetic effect that can further enhance oral cancer development.

Rictor and integrin-linked kinase interact and regulate Akt phosphorylation and cancer cell survival.

Science.gov (United States)

McDonald, Paul C; Oloumi, Arusha; Mills, Julia; Dobreva, Iveta; Maidan, Mykola; Gray, Virginia; Wederell, Elizabeth D; Bally, Marcel B; Foster, Leonard J; Dedhar, Shoukat

2008-03-15

An unbiased proteomic screen to identify integrin-linked kinase (ILK) interactors revealed rictor as an ILK-binding protein. This finding was interesting because rictor, originally identified as a regulator of cytoskeletal dynamics, is also a component of mammalian target of rapamycin complex 2 (mTORC2), a complex implicated in Akt phosphorylation. These functions overlap with known ILK functions. Coimmunoprecipitation analyses confirmed this interaction, and ILK and rictor colocalized in membrane ruffles and leading edges of cancer cells. Yeast two-hybrid assays showed a direct interaction between the NH(2)- and COOH-terminal domains of rictor and the ILK kinase domain. Depletion of ILK and rictor in breast and prostate cancer cell lines resulted in inhibition of Akt Ser(473) phosphorylation and induction of apoptosis, whereas, in several cell lines, depletion of mTOR increased Akt phosphorylation. Akt and Ser(473)P-Akt were detected in ILK immunoprecipitates and small interfering RNA-mediated depletion of rictor, but not mTOR, inhibited the amount of Ser(473)P-Akt in the ILK complex. Expression of the NH(2)-terminal (1-398 amino acids) rictor domain also resulted in the inhibition of ILK-associated Akt Ser(473) phosphorylation. These data show that rictor regulates the ability of ILK to promote Akt phosphorylation and cancer cell survival.

Mathematical modeling of tumor-associated macrophage interactions with the cancer microenvironment.

Science.gov (United States)

Mahlbacher, Grace; Curtis, Louis T; Lowengrub, John; Frieboes, Hermann B

2018-01-30

Immuno-oncotherapy has emerged as a promising means to target cancer. In particular, therapeutic manipulation of tumor-associated macrophages holds promise due to their various and sometimes opposing roles in tumor progression. It is established that M1-type macrophages suppress tumor progression while M2-types support it. Recently, Tie2-expressing macrophages (TEM) have been identified as a distinct sub-population influencing tumor angiogenesis and vascular remodeling as well as monocyte differentiation. This study develops a modeling framework to evaluate macrophage interactions with the tumor microenvironment, enabling assessment of how these interactions may affect tumor progression. M1, M2, and Tie2 expressing variants are integrated into a model of tumor growth representing a metastatic lesion in a highly vascularized organ, such as the liver. Behaviors simulated include M1 release of nitric oxide (NO), M2 release of growth-promoting factors, and TEM facilitation of angiogenesis via Angiopoietin-2 and promotion of monocyte differentiation into M2 via IL-10. The results show that M2 presence leads to larger tumor growth regardless of TEM effects, implying that immunotherapeutic strategies that lead to TEM ablation may fail to restrain growth when the M2 represents a sizeable population. As TEM pro-tumor effects are less pronounced and on a longer time scale than M1-driven tumor inhibition, a more nuanced approach to influence monocyte differentiation taking into account the tumor state (e.g., under chemotherapy) may be desirable. The results highlight the dynamic interaction of macrophages within a growing tumor, and, further, establish the initial feasibility of a mathematical framework that could longer term help to optimize cancer immunotherapy.

Molecular fundamentals of drug interactions in the therapy of colorectal cancer

Directory of Open Access Journals (Sweden)

Katarzyna Regulska

2014-03-01

Full Text Available Rapid advances in the field of chemotherapy have resulted in the introduction of numerous antineoplastic drugs into clinical practice, which increased the efficiency of patient management. Also the prevalent use of combination treatment based on drug action synergy contributed to the improved clinical effect associated with cytotoxic drug administration. It seems, however, obvious that the multidirectional pharmacotherapy in oncology requires a thorough knowledge of drugs’ pharmaceutical behavior in order to maximize their collective action and prevent the occurrence of unintended drug interactions that could potentially impair treatment effectiveness. In fact, drug interactions constitute a serious problem for current oncology primarily resulting from a narrow therapeutic index specific for the majority of anticancer drugs. This, in turn, indicates that even slight deviations of their pharmacokinetics could cause significant clinical consequences, manifested by alteration of the toxicological profile or reduction of therapeutic efficiency. Hence, the investigation of molecular aspects underlying the mechanisms of various drug interactions seems to be essential for proper and safe patient management. The present article is devoted to the extensive subject of drug interactions occurring in the therapy of colorectal cancer. It presents the available literature data on both positive and negative effects of interactions and it discusses their mechanisms complying with their classification into pharmacokinetic and pharmacodynamic ones.

[Molecular fundamentals of drug interactions in the therapy of colorectal cancer].

Science.gov (United States)

Regulska, Katarzyna; Stanisz, Beata; Regulski, Miłosz; Gieremek, Paulina

2014-03-04

Rapid advances in the field of chemotherapy have resulted in the introduction of numerous antineoplastic drugs into clinical practice, which increased the efficiency of patient management. Also the prevalent use of combination treatment based on drug action synergy contributed to the improved clinical effect associated with cytotoxic drug administration. It seems, however, obvious that the multidirectional pharmacotherapy in oncology requires a thorough knowledge of drugs' pharmaceutical behavior in order to maximize their collective action and prevent the occurrence of unintended drug interactions that could potentially impair treatment effectiveness. In fact, drug interactions constitute a serious problem for current oncology primarily resulting from a narrow therapeutic index specific for the majority of anticancer drugs. This, in turn, indicates that even slight deviations of their pharmacokinetics could cause significant clinical consequences, manifested by alteration of the toxicological profile or reduction of therapeutic efficiency. Hence, the investigation of molecular aspects underlying the mechanisms of various drug interactions seems to be essential for proper and safe patient management. The present article is devoted to the extensive subject of drug interactions occurring in the therapy of colorectal cancer. It presents the available literature data on both positive and negative effects of interactions and it discusses their mechanisms complying with their classification into pharmacokinetic and pharmacodynamic ones.

Gene Environment Interactions and Predictors of Colorectal Cancer in Family-Based, Multi-Ethnic Groups

Directory of Open Access Journals (Sweden)

S. Pamela K. Shiao

2018-02-01

Full Text Available For the personalization of polygenic/omics-based health care, the purpose of this study was to examine the gene–environment interactions and predictors of colorectal cancer (CRC by including five key genes in the one-carbon metabolism pathways. In this proof-of-concept study, we included a total of 54 families and 108 participants, 54 CRC cases and 54 matched family friends representing four major racial ethnic groups in southern California (White, Asian, Hispanics, and Black. We used three phases of data analytics, including exploratory, family-based analyses adjusting for the dependence within the family for sharing genetic heritage, the ensemble method, and generalized regression models for predictive modeling with a machine learning validation procedure to validate the results for enhanced prediction and reproducibility. The results revealed that despite the family members sharing genetic heritage, the CRC group had greater combined gene polymorphism rates than the family controls (p < 0.05, on MTHFR C677T, MTR A2756G, MTRR A66G, and DHFR 19 bp except MTHFR A1298C. Four racial groups presented different polymorphism rates for four genes (all p < 0.05 except MTHFR A1298C. Following the ensemble method, the most influential factors were identified, and the best predictive models were generated by using the generalized regression models, with Akaike’s information criterion and leave-one-out cross validation methods. Body mass index (BMI and gender were consistent predictors of CRC for both models when individual genes versus total polymorphism counts were used, and alcohol use was interactive with BMI status. Body mass index status was also interactive with both gender and MTHFR C677T gene polymorphism, and the exposure to environmental pollutants was an additional predictor. These results point to the important roles of environmental and modifiable factors in relation to gene–environment interactions in the prevention of CRC.

Disruption of PH–kinase domain interactions leads to oncogenic activation of AKT in human cancers

Science.gov (United States)

Parikh, Chaitali; Janakiraman, Vasantharajan; Wu, Wen-I; Foo, Catherine K.; Kljavin, Noelyn M.; Chaudhuri, Subhra; Stawiski, Eric; Lee, Brian; Lin, Jie; Li, Hong; Lorenzo, Maria N.; Yuan, Wenlin; Guillory, Joseph; Jackson, Marlena; Rondon, Jesus; Franke, Yvonne; Bowman, Krista K.; Sagolla, Meredith; Stinson, Jeremy; Wu, Thomas D.; Wu, Jiansheng; Stokoe, David; Stern, Howard M.; Brandhuber, Barbara J.; Lin, Kui; Skelton, Nicholas J.; Seshagiri, Somasekar

2012-01-01

The protein kinase v-akt murine thymoma viral oncogene homolog (AKT), a key regulator of cell survival and proliferation, is frequently hyperactivated in human cancers. Intramolecular pleckstrin homology (PH) domain–kinase domain (KD) interactions are important in maintaining AKT in an inactive state. AKT activation proceeds after a conformational change that dislodges the PH from the KD. To understand these autoinhibitory interactions, we generated mutations at the PH–KD interface and found that most of them lead to constitutive activation of AKT. Such mutations are likely another mechanism by which activation may occur in human cancers and other diseases. In support of this likelihood, we found somatic mutations in AKT1 at the PH–KD interface that have not been previously described in human cancers. Furthermore, we show that the AKT1 somatic mutants are constitutively active, leading to oncogenic signaling. Additionally, our studies show that the AKT1 mutants are not effectively inhibited by allosteric AKT inhibitors, consistent with the requirement for an intact PH–KD interface for allosteric inhibition. These results have important implications for therapeutic intervention in patients with AKT mutations at the PH–KD interface. PMID:23134728

Breast Cancer Screening Coverage with clinical examination and Mammography Among insured women in Bogota

International Nuclear Information System (INIS)

Arboleda, Walter; Murillo Raul; Pinero, Marion

2009-01-01

The objective is to determine the coverage of clinical breast examination (CBE) and mammography for screening of breast cancer among a group of insured women in Bogota. Methods: A telephone survey was carried out with 4,526 women between the ages of 50 and 69, residing in Bogota or its suburbs, who were insured by one of three commercial health plans. Women with a history of breast cancer were excluded. Screening coverage was estimated as the proportion of women who had had a mammography or CBE. Estimates were established for lifetime frequency, two years prior the survey, and one year prior the survey. Factors associated with screening procedures were analyzed with calculations based on adjusted OR. Results: Lifetime frequency of CBE was 59.3% and 79.8% for mammography; and 49.7% and 65.6% of women respectively underwent the tests for screening purposes; the remainder, for diagnostic purposes (breast symptoms). CBE reported a 34.2% one year coverage and mammography reported a 54% two years coverage. Screening was associated to cancer education and family history of breast cancer. Conclusion: Coverage of CBE for screening purposes is low. Mammography coverage is above that required by the Colombian Health Ministry, but below that reported by developed countries.

Prevalence of high-grade squamous intraepithelial lesions and cervical cancer among patients with unsatisfactory colposcopic examination, without visible lesion

Directory of Open Access Journals (Sweden)

Fernanda Rangel da Veiga

Full Text Available CONTEXT AND OBJECTIVE: Cervical cancer is a serious public health problem in Brazil. For patients with unsatisfactory colposcopic examinations without visible lesions, but with cervical cytological tests suggesting high-grade squamous intraepithelial lesion (HSIL, the national recommendation is to repeat cervical cytological tests after three months. Our aim was to assess the prevalence of HSIL and cancer among patients with initial cervical cytological tests suggestive of HSIL but with unsatisfactory colposcopic examinations without visible lesions, in order to contribute towards the discussion regarding a more effective clinical approach that might diminish the likelihood of patient abandonment of follow-up before appropriate diagnosis and treatment. DESIGN AND SETTING: Cross-sectional study in Colposcopy Clinic of IFF/Fiocruz. METHOD: Patients admitted between December 1989 and April 2007 with cytological diagnoses of HSIL but with unsatisfactory colposcopic examinations without visible lesions underwent cervical cone biopsy. RESULTS: Sixty-five such patients were included, comprising 33.8% with HSIL and 4.6% with cancer, confirmed histologically. The other patients presented low-grade squamous intraepithelial lesion (26.1%, glandular dysplasia (1.5% and absence of disease (33.8%. CONCLUSION: The observed prevalence of cancer and HSIL does not seem to be enough to justify immediate referral for cone biopsies to investigate the cervical canal in these cases. The findings suggest that the recommendation of repeated cytological tests following an initial one with HSIL, among patients with unsatisfactory colposcopic examinations without visible lesions, is appropriate in our setting. Efforts are needed to ensure adherence to follow-up protocols in order to reduce the chances of losses.

Lipid raft-mediated miR-3908 inhibition of migration of breast cancer cell line MCF-7 by regulating the interactions between AdipoR1 and Flotillin-1.

Science.gov (United States)

Li, Yuan; Shan, Fei; Chen, Jinglong

2017-03-21

The mechanisms of lipid raft regulation by microRNAs in breast cancer are not fully understood. This work focused on the evaluation and identification of miR-3908, which may be a potential biomarker related to the migration of breast cancer cells, and elucidates lipid-raft-regulating cell migration in breast cancer. To confirm the prediction that miR-3908 is matched with AdipoR1, we used 3'-UTR luciferase activity of AdipoR1 to assess this. Then, human breast cancer cell line MCF-7 was cultured in the absence or presence of the mimics or inhibitors of miR-3908, after which the biological functions of MCF-7 cells were analyzed. The protein expression of AdipoR1, AMPK, and SIRT-1 were examined. The interaction between AdipoR1 and Flotillin-1, or its effects on lipid rafts on regulating cell migration of MCF-7, was also investigated. AdipoR1 is a direct target of miR-3908. miR-3908 suppresses the expression of AdipoR1 and its downstream pathway genes, including AMPK, p-AMPK, and SIRT-1. miR-3908 enhances the process of breast cancer cell clonogenicity. miR-3908 exerts its effects on the proliferation and migration of MCF-7 cells, which are mediated by lipid rafts regulating AdipoR1's ability to bind Flotillin-1. miR-3908 is a crucial mediator of the migration process in breast cancer cells. Lipid rafts regulate the interactions between AdipoR1 and Flotillin-1 and then the migration process associated with miR-3908 in MCF-7 cells. Our findings suggest that targeting miR-3908 and the lipid raft, may be a promising strategy for the treatment and prevention of breast cancer.

Meat and fiber intake and interaction with pattern recognition receptors (TLR1, TLR2, TLR4, and TLR10) in relation to colorectal cancer in a Danish prospective, case-cohort study

DEFF Research Database (Denmark)

Kopp, Tine Iskov; Vogel, Ulla; Tjonneland, Anne

2018-01-01

Background: Meat and dietary fiber are associated with increased and decreased risk of colorectal cancer (CRC), respectively. Toll-like receptors (TLRs) regulate the intestinal immune response in a complex interplay between the mucosal epithelium and the microbiota and may therefore be important...... modulators of diet-induced CRC together with other inflammatory mediators. Objective: Our aim was to investigate the association between functional TLR polymorphisms and risk of CRC and the interaction with dietary factors. Additionally, interactions with previously studied polymorphisms in IL10, IL1B, PTGS2......, and NFKB1 were assessed in order to examine possible biological pathways in meat-induced CRC. Design: A nested case-cohort study of 897 CRC cases and 1689 randomly selected participants from the Danish prospective "Diet, Cancer and Health" study encompassing 57,053 persons was performed using Cox...

Gynecologic examination and cervical biopsies after (chemo) radiation for cervical cancer to identify patients eligible for salvage surgery

International Nuclear Information System (INIS)

Nijhuis, Esther R.; Zee, Ate G.J. van der; Hout, Bertha A. in 't; Boomgaard, Jantine J.; Hullu, Joanne A. de; Pras, Elisabeth; Hollema, Harry; Aalders, Jan G.; Nijman, Hans W.; Willemse, Pax H.B.; Mourits, Marian J.E.

2006-01-01

Purpose: The aim of this study was to evaluate efficacy of gynecologic examination under general anesthesia with cervical biopsies after (chemo) radiation for cervical cancer to identify patients with residual disease who may benefit from salvage surgery. Methods and Materials: In a retrospective cohort study data of all cervical cancer patients with the International Federation of Gynecology and Obstetrics (FIGO) Stage IB1 to IVA treated with (chemo) radiation between 1994 and 2001 were analyzed. Patients underwent gynecologic examination under anesthesia 8 to 10 weeks after completion of treatment. Cervical biopsy samples were taken from patients judged to be operable. In case of residual cancer, salvage surgery was performed. Results: Between 1994 and 2001, 169 consecutive cervical cancer patients received primary (chemo) radiation, of whom 4 were lost to follow-up. Median age was 56 years (interquartile range [IQR], 44-71) and median follow-up was 3.5 years (IQR, 1.5-5.9). In each of 111 patients a biopsy sample was taken, of which 90 (81%) showed no residual tumor. Vital tumor cells were found in 21 of 111 patients (19%). Salvage surgery was performed in 13 of 21 (62%) patients; of these patients, 5 (38%) achieved long-term, complete remission after salvage surgery (median follow-up, 5.2 years; range, 3.9-8.8 years). All patients with residual disease who did not undergo operation (8/21) died of progressive disease. Locoregional control was more often obtained in patients who underwent operation (7 of 13) than in patients who were not selected for salvage surgery (0 of 8 patients) (p < 0.05). Conclusions: Gynecologic examination under anesthesia 8 to 10 weeks after (chemo) radiation with cervical biopsies allows identification of those cervical cancer patients who have residual local disease, of whom a small but significant proportion may be salvaged by surgery

Active smoking and survival following breast cancer among African American and non-African American women in the Carolina Breast Cancer Study.

Science.gov (United States)

Parada, Humberto; Sun, Xuezheng; Tse, Chiu-Kit; Olshan, Andrew F; Troester, Melissa A; Conway, Kathleen

2017-09-01

To examine racial differences in smoking rates at the time of breast cancer diagnosis and subsequent survival among African American and non-African American women in the Carolina Breast Cancer Study (Phases I/II), a large population-based North Carolina study. We interviewed 788 African American and 1,020 Caucasian/non-African American women diagnosed with invasive breast cancer from 1993 to 2000, to assess smoking history. After a median follow-up of 13.56 years, we identified 717 deaths using the National Death Index; 427 were breast cancer-related. We used Cox regression to examine associations between self-reported measures of smoking and breast cancer-specific survival within 5 years and up to 18 years after diagnosis conditional on 5-year survival. We examined race and estrogen receptor status as potential modifiers. Current (vs never) smoking was not associated with 5-year survival; however, risk of 13 year conditional breast cancer-specific mortality was elevated among women who were current smokers at diagnosis (HR 1.54, 95% CI 1.06-2.25), compared to never smokers. Although smoking rates were similar among African American (22.0%) and non-African American (22.1%) women, risk of breast cancer-specific mortality was elevated among African American (HR 1.69, 95% CI 1.00-2.85), but only weakly elevated among non-African American (HR 1.22, 95% CI 0.70-2.14) current (vs. never) smokers (P Interaction  = 0.30). Risk of breast cancer-specific mortality was also elevated among current (vs never) smokers diagnosed with ER - (HR 2.58, 95% CI 1.35-4.93), but not ER + (HR 1.11, 95% CI 0.69-1.78) tumors (P Interaction  = 0.17). Smoking may negatively impact long-term survival following breast cancer. Racial differences in long-term survival, as related to smoking, may be driven by ER status, rather than by differences in smoking patterns.

Comparison of 4 established DASH diet indexes: examining associations of index scores and colorectal cancer123

Science.gov (United States)

Cross, Amanda J; Subar, Amy F; Krebs-Smith, Susan M; Park, Yikyung; Powell-Wiley, Tiffany; Hollenbeck, Albert; Reedy, Jill

2013-01-01

Background: Multiple diet indexes have been developed to capture the Dietary Approaches to Stop Hypertension (DASH) dietary pattern and examine relations with health outcomes but have not been compared within the same study population to our knowledge. Objective: We compared 4 established DASH indexes and examined associations with colorectal cancer. Design: Scores were generated from a food-frequency questionnaire in the NIH-AARP Diet and Health Study (n = 491,841). Separate indexes defined by Dixon (7 food groups, saturated fat, and alcohol), Mellen (9 nutrients), Fung (7 food groups and sodium), and Günther (8 food groups) were used. HRs and 95% CIs for colorectal cancer were generated by using Cox proportional hazard models. Results: From 1995 through 2006, 6752 incident colorectal cancer cases were ascertained. In men, higher scores were associated with reduced colorectal cancer incidence by comparing highest to lowest quintiles for all indexes as follows: Dixon (HR: 0.77; 95% CI: 0.69, 0.87), Mellen (HR: 0.78; 95% CI: 0.71, 0.86), Fung (HR: 0.75; 95% CI: 0.68, 0.83), and Günther (HR: 0.81; 95% CI: 0.74, 0.90). Higher scores in women were inversely associated with colorectal cancer incidence by using methods defined by Mellen (HR: 0.79; 95% CI: 0.68, 0.91), Fung (HR: 0.84; 95% CI: 0.73, 0.96), and Günther (HR: 0.84; 95% CI: 0.73.0.97) but not Dixon (HR: 1.01; 95% CI: 0.80, 1.28). Conclusion: The consistency in findings, particularly in men, suggests that all indexes capture an underlying construct inherent in the DASH dietary pattern, although the specific index used can affect results. PMID:23864539

Interaction between ADH1C Arg272Gln and alcohol intake in relation to breast cancer risk suggests that ethanol is the causal factor in alcohol related breast cancer

DEFF Research Database (Denmark)

Benzon Larsen, Signe; Vogel, Ulla Birgitte; Christensen, Jane

2010-01-01

Alcohol is a risk factor for breast cancer. We wanted to determine if ADH polymorphisms which modify the rate of ethanol oxidation to acetaldehyde, were associated with breast cancer risk. We matched 809 postmenopausal breast cancer cases with 809 controls, nested within the prospective Diet......, Cancer and Health study. Among variant allele carriers of ADH1C Arg(272)Gln, alcohol intake increased the risk of breast cancer with 14% (95% CI: 1.04-1.24) per 10g alcohol/day, but not among homozygous wild type carriers (p for interaction=0.06). Thus, slow oxidation of ethanol seemed to be associated...

Changes in frequency of recall recommendations of examinations depicting cancer with the availability of either priors or digital breast tomosynthesis

Science.gov (United States)

Hakim, Christiane M.; Bandos, Andriy I.; Ganott, Marie A.; Catullo, Victor J.; Chough, Denise M.; Kelly, Amy E.; Shinde, Dilip D.; Sumkin, Jules H.; Wallace, Luisa P.; Nishikawa, Robert M.; Gur, David

2016-03-01

Performance changes in a binary environment when using additional information is affected only when changes in recommendations are made due to the additional information in question. In a recent study, we have shown that, contrary to general expectation, introducing prior examinations improved recall rates, but not sensitivity. In this study, we assessed cancer detection differences when prior examinations and/or digital breast tomosynthesis (DBT) were made available to the radiologist. We identified a subset of 21 cancer cases with differences in the number of radiologists who recalled these cases after reviewing either a prior examination or DBT. For the cases with differences in recommendations after viewing either priors or DBT, separately, we evaluated the total number of readers that changed their recommendations, regardless of the specific radiologist in question. Confidence intervals for the number of readers and a test for the hypothesis of no difference was performed using the non-parameteric bootstrap approach addressing both case and reader-related sources of variability by resampling cases and readers. With the addition of priors, there were 14 cancer cases (out of 15) where the number of "recalling radiologists" decreased. With the addition of DBT, the number of "recalling radiologists" decreased in only five cases (out of 15) while increasing in the remaining 9 cases. Unlike most new approaches to breast imaging DBT seems to improve both recall rates and cancer detection rates. Changes in recommendations were noted by all radiologists for all cancers by type, size, and breast density.

Thermodesorption examination of interaction of hydrogen with traps in silver

International Nuclear Information System (INIS)

Gabis, I.E.; Kurdyumov, A.A.; Ovsvannikova, T.A.

1992-01-01

The authors have previously examined the interaction of hydrogen with silver by the methods of thermal desorption spectrometry (TDS) and hydrogen permeability. The results showed that the TDS spectra contained a high-temperature phase linked with hydrogen which left the volume of the specimen during heating. It was assumed that hydrogen was captured and released by structural defects acting as traps. These traps can be represented by vacancies and their clusters. In this work, the high-temperature desorption of hydrogen from silver was studied. The experimental setup consisted of an all-metal vacuum system, a time-of-flight mass spectrometer, a DVK-2M computing system, and a Camac system. The described model of a local equilibrium should be regarded only as a first approximation. The results provide unambiguous information on the processes of permeability and desorption, and make it possible to assume that the formation of the high-temperature phase in TD spectra was caused by the generation of hydrogen from the traps. The parameters of the interaction of hydrogen with the traps were determined by the concentration wave method. 7 refs., 2 figs

Re-examining the factor structure and psychometric properties of the Mini-Mental Adjustment to Cancer Scale in a sample of 364 Chinese cancer patients.

Science.gov (United States)

Fong, Ted C T; Ho, Rainbow T H

2015-02-01

The Mini-Mental Adjustment to Cancer Scale (Mini-MAC) is widely used to evaluate cancer patients' psychological responses. Validation studies of the scale have shown methodological shortcomings and inconsistency in the factor solutions. The aim of this study was to examine the factor structure and psychometric properties of the Mini-MAC. A large sample of 364 Chinese patients with breast or colorectal cancer completed the Mini-MAC and psychosocial measures (general health, perceived stress, anxiety, and depression). Exploratory factor analyses examined the relative fit of two- to six-factor models using robust weighted least square estimation and oblique target rotation. Convergent validity was evaluated via correlations between the Mini-MAC factor scores and the psychosocial outcomes. The five-factor model showed the best model fit and largely replicated the original Mini-MAC's helpless/hopeless (HH), anxious preoccupation (AP), fighting spirit (FS), fatalism (FA), and cognitive avoidance (CA) subscales. The five factors had acceptable reliability (Cronbach's α = 0.67-0.88) and 4-month test-retest reliability (r = 0.45-0.64). HH, AP, and CA were positively associated with the psychosocial outcomes (r = 0.19-0.60). Modest and negative correlations were found between the psychosocial outcomes and FS and FA. The results support the Mini-MAC's original five-factor structure with satisfactory reliability and convergent validity. The results demonstrate that the Mini-MAC is a valid measure for assessing psychological responses in cancer patients.

Effects of temperature and cellular interactions on the mechanics and morphology of human cancer cells investigated by atomic force microscopy.

Science.gov (United States)

Li, Mi; Liu, LianQing; Xi, Ning; Wang, YueChao; Xiao, XiuBin; Zhang, WeiJing

2015-09-01

Cell mechanics plays an important role in cellular physiological activities. Recent studies have shown that cellular mechanical properties are novel biomarkers for indicating the cell states. In this article, temperature-controllable atomic force microscopy (AFM) was applied to quantitatively investigate the effects of temperature and cellular interactions on the mechanics and morphology of human cancer cells. First, AFM indenting experiments were performed on six types of human cells to investigate the changes of cellular Young's modulus at different temperatures and the results showed that the mechanical responses to the changes of temperature were variable for different types of cancer cells. Second, AFM imaging experiments were performed to observe the morphological changes in living cells at different temperatures and the results showed the significant changes of cell morphology caused by the alterations of temperature. Finally, by co-culturing human cancer cells with human immune cells, the mechanical and morphological changes in cancer cells were investigated. The results showed that the co-culture of cancer cells and immune cells could cause the distinct mechanical changes in cancer cells, but no significant morphological differences were observed. The experimental results improved our understanding of the effects of temperature and cellular interactions on the mechanics and morphology of cancer cells.

The ExPeCT (Examining Exercise, Prostate Cancer and Circulating Tumour Cells) trial: study protocol for a randomised controlled trial.

LENUS (Irish Health Repository)

Sheill, Gráinne

2017-10-04

Prostate cancer (PrCa) is the second most common cancer in Ireland. Many men present with locally advanced or metastatic cancer for whom curative surgery is inappropriate. Advanced cancer patients are encouraged to remain physically active and therefore there is a need to investigate how patients with metastatic disease tolerate physical activity programmes. Physical activity reduces levels of systemic inflammatory mediators and so an aerobic exercise intervention may represent an accessible and cost-effective means of ameliorating the pro-inflammatory effects of obesity and subsequently decrease poor cancer-specific outcomes in this patient population. This study will assess the feasibility and safety of introducing a structured aerobic exercise intervention to an advanced cancer population. This study will also examine if the evasion of immune editing by circulating tumour cells (CTCs) is an exercise-modifiable mechanism in obese men with prostate cancer.

Examining ecological validity in social interaction: problems of visual fidelity, gaze, and social potential.

Science.gov (United States)

Reader, Arran T; Holmes, Nicholas P

2016-01-01

Social interaction is an essential part of the human experience, and much work has been done to study it. However, several common approaches to examining social interactions in psychological research may inadvertently either unnaturally constrain the observed behaviour by causing it to deviate from naturalistic performance, or introduce unwanted sources of variance. In particular, these sources are the differences between naturalistic and experimental behaviour that occur from changes in visual fidelity (quality of the observed stimuli), gaze (whether it is controlled for in the stimuli), and social potential (potential for the stimuli to provide actual interaction). We expand on these possible sources of extraneous variance and why they may be important. We review the ways in which experimenters have developed novel designs to remove these sources of extraneous variance. New experimental designs using a 'two-person' approach are argued to be one of the most effective ways to develop more ecologically valid measures of social interaction, and we suggest that future work on social interaction should use these designs wherever possible.

Killing of melanoma cells and their metastases by human lactoferricin derivatives requires interaction with the cancer marker phosphatidylserine.

Science.gov (United States)

Riedl, Sabrina; Rinner, Beate; Schaider, Helmut; Lohner, Karl; Zweytick, Dagmar

2014-10-01

Despite favorable advancements in therapy cancer is still not curative in many cases, which is often due to inadequate specificity for tumor cells. In this study derivatives of a short cationic peptide derived from the human host defense peptide lactoferricin were optimized in their selective toxicity towards cancer cells. We proved that the target of these peptides is the negatively charged membrane lipid phosphatidylserine (PS), specifically exposed on the surface of cancer cells. We have studied the membrane interaction of three peptides namely LF11-322, its N-acyl derivative 6-methyloctanoyl-LF11-322 and its retro repeat derivative R(etro)-DIM-P-LF11-322 with liposomes mimicking cancerous and non-cancerous cell membranes composed of PS and phosphatidylcholine (PC), respectively. Calorimetric and permeability studies showed that N-acylation and even more the repeat derivative of LF11-322 leads to strongly improved interaction with the cancer mimic PS, whereas only the N-acyl derivative also slightly affects PC. Tryptophan fluorescence of selective peptide R-DIM-P-LF11-322 revealed specific peptide penetration into the PS membrane interface and circular dichroism showed change of its secondary structure by increase of proportion of β-sheets just in the presence of the cancer mimic. Data correlated with in vitro studies with cell lines of human melanomas, their metastases and melanocytes, revealing R-DIM-P-LF11-322 to exhibit strongly increased specificity for cancer cells. This indicates the need of high affinity to the target PS, a minimum length and net positive charge, an adequate but moderate hydrophobicity, and capability of adoption of a defined structure exclusively in presence of the target membrane for high antitumor activity.

Vitamin C supplement intake and postmenopausal breast cancer risk: interaction with dietary vitamin C.

Science.gov (United States)

Cadeau, Claire; Fournier, Agnès; Mesrine, Sylvie; Clavel-Chapelon, Françoise; Fagherazzi, Guy; Boutron-Ruault, Marie-Christine

2016-07-01

Experimental and epidemiologic studies have yielded conflicting results on the relation between vitamin C intake and breast cancer risk. We investigated the relation between vitamin C supplement intake and breast cancer risk while considering dietary vitamin C intake. Between 1995 and 2008, 2482 invasive breast cancer cases occurred in 57,403 postmenopausal women from the Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale (E3N) prospective cohort during 581,085 person-years. We estimated vitamin C intake from foods with the use of a validated food-frequency questionnaire that was sent to subjects in 1993-1995 and vitamin C supplement use via questionnaires sent in 1995, 2000, 2002, and 2005. Multivariable HRs (95% CIs) for primary invasive breast cancer were estimated with the use of Cox regression models. All statistical tests were 2-sided. Vitamin C supplement use (ever compared with never) was not associated with breast cancer risk overall; it was associated with higher breast cancer risk in women in the fourth quartile of vitamin C intake from foods (HR: 1.32; 95% CI: 1.04, 1.67) but not in other quartiles of dietary vitamin C intake (P-interaction = 0.03). We observed that vitamin C supplement use was associated with increased postmenopausal breast cancer risk in women with high vitamin C intake from foods. Our data suggest a potential U- or J-shaped relation between total vitamin C intake and postmenopausal breast cancer risk that deserves further investigation. © 2016 American Society for Nutrition.

Yazd Breast Cancer Project Profile; A Community Based Trial for the Evaluation of Self-Examination and Physical Examination of the Breast Cancer Disease

Directory of Open Access Journals (Sweden)

Anthony B Miller

2015-11-01

Full Text Available There is some evidence to suggest that a benefit might be derived from a program that incorporated both annual physical examination of the breast (BPx and the teaching of breast self-examination (BSE. Current investigation presents the profile of a multicenter community based intervention for evaluating the effect of BSE+BPx on the reduction of morbidity and mortality due to breast cancer amongst women residing in urban areas of Yazd (Iran from 2008 to 2018. There were three distinctive phases in this trial with 10 years duration: pilot phase with the duration of 1 year, active intervention phase with 4 rounds of annual screening of BPx+BSE and follow up phase with 5 years duration. Tools of enquiry included a pre-tested questionnaire, repeated annual physical examination of the breast and more importantly mammography, sonography, and fine needle aspiration (FNA. Data were analyzed using descriptive statistics such as frequencies, percent, mean (SD, tests of chi-square and student t-test with 95% confidence level. Comparison of socio-demographic and socio-economic factors such as age, age at marriage, family size, number of live births, occupation, education level, total family income and marital status showed that no significant difference was seen between the groups (P>0.05. A response rate of 84.5% was seen by participants of the experiment group visiting the health centers for the first BPx. Our results showed that except for the education and marital status, the difference in other main demographic and socio-economic factors between the groups were not significant, and the response rate of individuals in the experiment group was at an acceptable level.

Awareness of Cancer Susceptibility Genetic Testing

Science.gov (United States)

Mai, Phuong L.; Vadaparampil, Susan Thomas; Breen, Nancy; McNeel, Timothy S.; Wideroff, Louise; Graubard, Barry I.

2014-01-01

Background Genetic testing for several cancer susceptibility syndromes is clinically available; however, existing data suggest limited population awareness of such tests. Purpose To examine awareness regarding cancer genetic testing in the U.S. population aged ≥25 years in the 2000, 2005, and 2010 National Health Interview Surveys. Methods The weighted percentages of respondents aware of cancer genetic tests, and percent changes from 2000–2005 and 2005–2010, overall and by demographic, family history, and healthcare factors were calculated. Interactions were used to evaluate the patterns of change in awareness between 2005 and 2010 among subgroups within each factor. To evaluate associations with awareness in 2005 and 2010, percentages were adjusted for covariates using multiple logistic regression. The analysis was performed in 2012. Results Awareness decreased from 44.4% to 41.5% (pAwareness increased between 2005 and 2010 in most subgroups, particularly among individuals in the South (p-interaction=0.03) or with a usual place of care (p-interaction=0.01). In 2005 and 2010, awareness was positively associated with personal or family cancer history and high perceived cancer risk, and inversely associated with racial/ethnic minorities, age 25–39 or ≥60 years, male gender, lower education and income levels, public or no health insurance, and no provider contact in 12 months. Conclusions Despite improvement from 2005 to 2010, ≤50% of the U.S. adult population was aware of cancer genetic testing in 2010. Notably, disparities persist for racial/ethnic minorities and individuals with limited health care access or income. PMID:24745633

Regulation of HGF and c-MET Interaction in Normal Ovary and Ovarian Cancer.

Science.gov (United States)

Kwon, Youngjoo; Godwin, Andrew K

2017-04-01

Binding of hepatocyte growth factor (HGF) to the c-MET receptor has mitogenic, motogenic, and morphogenic effects on cells. The versatile biological effects of HGF and c-MET interactions make them important contributors to the development of malignant tumors. We and others have demonstrated a therapeutic value in targeting the interaction of c-MET and HGF in epithelial ovarian cancer (EOC). However, both HGF and c-MET are expressed in the normal ovary as well. Therefore, it is important to understand the differences in mechanisms that control HGF signaling activation and its functional role in the normal ovary and EOC. In the normal ovary, HGF signaling may be under hormonal regulation. During ovulation, HGF-converting proteases are secreted and the subsequent activation of HGF signaling enhances the proliferation of ovarian surface epithelium in order to replenish the area damaged due to expulsion of the ovum. In contrast, EOC cells that exhibit epithelial characteristics constitutively express both c-MET and HGF-converting proteases such as urokinase-type plasminogen activator. In EOC, mechanisms to control the activation of HGF signaling are absent since HGF is provided locally from the tissue microenvironment as well as remotely throughout the body. Potential incessant HGF signaling in EOC may lead to an increase in proliferation, invasion through the stroma, and migration to other tissues of cancer cells. Therefore, targeting the interaction of c-MET and HGF would be beneficial in treating EOC.

Discoidin domain receptor 1 activity drives an aggressive phenotype in bladder cancer

OpenAIRE

Xie, Xin; Rui, Wenbin; He, Wei; Shao, Yuan; Sun, Fukang; Zhou, Wenlong; Wu, Yuxuan; Zhu, Yu

2017-01-01

Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase which utilizes collagen as a ligand to regulate the interaction between cancer cells and tumor stroma. However, the clinical relevance of DDR1 expression in bladder cancer as well as its molecular regulation have not been previously investigated. Here, we assessed the role of DDR1 in bladder cancer. The DDR1 levels in bladder cancer specimens were examined by Western blot, compared to the paired adhesive normal controls. The eff...

Targeting Hsp27/eIF4E interaction with phenazine compound: a promising alternative for castration-resistant prostate cancer treatment.

Science.gov (United States)

Hajer, Ziouziou; Claudia, Andrieu; Erik, Laurini; Sara, Karaki; Maurizio, Fermeglia; Ridha, Oueslati; David, Taieb; Michel, Camplo; Olivier, Siri; Sabrina, Pricl; Maria, Katsogiannou; Palma, Rocchi

2017-09-29

The actual strategy to improve current therapies in advanced prostate cancer involves targeting genes activated by androgen withdrawal, either to delay or prevent the emergence of the castration-refractory phenotype. However, these genes are often implicated in several physiological processes, and long-term inhibition of survival proteins might be accompanied with cytotoxic effects. To avoid this problem, an alternative therapeutic strategy relies on the identification and use of compounds that disrupt specific protein-protein interactions involved in androgen withdrawal. Specifically, the interaction of the chaperone protein Hsp27 with the initiation factor eIF4E leads to the protection of protein synthesis initiation process and enhances cell survival during cell stress induced by castration or chemotherapy. Thus, in this work we aimed at i) identifying the interaction site of the Hsp27/eIF4E complex and ii) interfere with the relevant protein/protein association mechanism involved in castration-resistant progression of prostate cancer. By a combination of experimental and modeling techniques, we proved that eIF4E interacts with the C-terminal part of Hsp27, preferentially when Hsp27 is phosphorylated. We also observed that the loss of this interaction increased cell chemo-and hormone-sensitivity. In order to find a potential inhibitor of Hsp27/eIF4E interaction, BRET assays in combination with molecular simulations identified the phenazine derivative 14 as the compound able to efficiently interfere with this protein/protein interaction, thereby inhibiting cell viability and increasing cell death in chemo- and castration-resistant prostate cancer models in vitro and in vivo .

Interaction of nitrate and folate on the risk of breast cancer among postmenopausal women.

Science.gov (United States)

Inoue-Choi, Maki; Ward, Mary H; Cerhan, James R; Weyer, Peter J; Anderson, Kristin E; Robien, Kim

2012-01-01

Ingested nitrate can be endogenously reduced to nitrite, which may form N-nitroso compounds, known potent carcinogens. However, some studies have reported no or inverse associations between dietary nitrate intake and cancer risk. These associations may be confounded by a protective effect of folate, which plays a vital role in DNA repair. We evaluated the interaction of dietary and water nitrate intake with total folate intake on breast cancer risk in the Iowa Women's Health Study. Dietary intake was assessed at study baseline. Nitrate intake from public water was assessed using a historical database on Iowa municipal water supplies. After baseline exclusions, 34,388 postmenopausal women and 2,875 incident breast cancers were included. Overall, neither dietary nor water nitrate was associated with breast cancer risk. Among those with folate intake ≥400 μg/day, breast cancer risk was significantly increased in public water users with the highest nitrate quintile (HR = 1.40, 95% CI = 1.05-1.87) and private well users (HR = 1.38, 95% CI = 1.05-1.82) compared to public water users with the lowest nitrate quintile; in contrast, there was no association among those with lower folate intake. Our findings do not support a previous report of increased risk of breast cancer among individuals with high dietary nitrate but low folate intake.

Functional interactivity in social media: an examination of Chinese health care organizations' microblog profiles.

Science.gov (United States)

Jiang, Shaohai

2017-09-08

Social media hold enormous potentials as a communication tool for health care due to its interactive nature. However, prior research mainly focused on contingency interactivity of social media, by examining messages sent from health care organizations to audiences, while little is known about functional interactivity, which refers to social media's presence of functions for facilitating communication between users and its interface. That is, how health care organizations use interactive features on social media to communicate with the public. Thus, with a general basis of the functional interactivity framework proposed by Waters et al. (Engaging stakeholders through social networking: how nonprofit organizations are using Facebook. Pub Relat Rev 2009;35:102-106), the current study investigated three aspects of functional interactivity in microblogging, and its subsequent effects. Specifically, this study analyzed 500 Chinese hospitals' profiles on Sina Weibo, the most popular microblogging platform in China. The results showed that the most common functional interactivity feature was organization disclosure, followed by information dissemination, and audience involvement. These interactive features all positively predicted the number of followers. Also, Chinese private hospitals scored significantly higher than public hospitals to use interactive features offered by social media. The findings of this study provide important implications for health care organizations to understand new communicative functions available on social media, incorporate more functions into their profiles and thus provide audiences with greater opportunity to interact with them via social media. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Vegetable and animal products as determinants of colon cancer risk in Dutch men and women

NARCIS (Netherlands)

Kampman, E.; Verhoeven, D.; Sloots, L.; Veer, P. van 't

1995-01-01

To examine the relationship between colon cancer and food groups from vegetable or animal sources and their possible interactions with gender, we analyzed data from a Dutch case-control study. Dietary patterns were assessed for 232 colon cancer cases and 259 population controls. In multivariate

A retrospective outcomes study examining the effect of interactive metronome on hand function.

Science.gov (United States)

Shank, Tracy M; Harron, Wendy

2015-01-01

Interactive Metronome (IM, The Interactive Metronome Company, Sunrise, Florida, USA) is a computer-based modality marketed to rehabilitation professionals who want to improve outcomes in areas of coordination, motor skills, self-regulation behaviors, and cognitive skills. This retrospective study examined the efficacy of IM training on improving timing skills, hand function, and parental report of self-regulatory behaviors. Forty eight children with mixed motor and cognitive diagnoses completed an average of 14 one-hour training sessions over an average of 8.5 weeks in an outpatient setting. Each child was assessed before and after training with the Interactive Metronome Long Form Assessment, the Jebsen Taylor Test of Hand Function, and a parent questionnaire. All three measures improved with statistical significance despite participants having no direct skill training. These results suggest an intimate relationship between cognition and motor skills that has potential therapeutic value. Level 4, Retrospective Case Series. Copyright © 2015 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

The cancer stem cell marker CD133 interacts with plakoglobin and controls desmoglein-2 protein levels.

Directory of Open Access Journals (Sweden)

Ryo Koyama-Nasu

Full Text Available The pentaspan membrane glycoprotein CD133 (also known as prominin-1 has been widely used as a marker for both cancer and normal stem cells. However, the function of CD133 has not been elucidated. Here we describe a cancer stem cell line established from clear cell carcinoma of the ovary (CCC and show that CD133 interacts with plakoglobin (also known as γ-catenin, a desmosomal linker protein. We further demonstrate that knockdown of CD133 by RNA interference (RNAi results in the downregulation of desmoglein-2, a desmosomal cadherin, and abrogates cell-cell adhesion and tumorigenicity of CCC stem cells. We speculate that CD133 may be a promising target for cancer chemotherapy.

Sexual potency following interactive ultrasound-guided brachytherapy for prostate cancer

International Nuclear Information System (INIS)

Stock, Richard G.; Stone, Nelson N.; Iannuzzi, Christopher

1996-01-01

Purpose: The effect of a therapeutic modality on sexual potency is often an important consideration for patients choosing a treatment for prostate cancer. We prospectively assessed patients' penile erectile function before and following interactive ultrasound-guided transperineal permanent radioactive seed implantation to determine its effect on sexual function. Methods and Materials: Eighty-nine patients underwent permanent radioactive seed implantation from June 1990 to April 1994 for localized prostate cancer (T1-T2) and were followed for a median of 15 months (1.5-52 months). 125 I seeds were implanted in 73 patients with a combined Gleason grade of 2-6, and 103 Pd seeds were implanted in 16 patients with higher grade lesions. The sexual potency of these patients was assessed prior to, at 3 and 6 months, and every 6 months after implantation. Erectile function was graded using a numerical score of 0 to 3 (0 = impotent (no erections), 1 = ability to have erections but insufficient for vaginal penetration, 2 = erectile function sufficient for vaginal penetration but suboptimal, 3 = normal erectile function). The pretreatment potency scores were as follows: 0 in 24 patients, 1 in 6 patients, 2 in 22 patients, and 3 in 37 patients. Results: The actuarial impotency rates (score = 0) following implantation for those patients possessing some degree of erectile function prior to implantation (65 patients) were 2.5% at 1 year and 6% at 2 years. The actuarial decrease in sexual function rates (a drop in score of at least one point) were 29% at 1 year and 39% at 2 years. Only two patients became impotent following treatment and this occurred at 1 year and 16 months. The time period for a decrease in erectile function to occur ranged from 1.8 months to 32.7 months, with a median of 6.8 months. Patients with higher grade tumors showed a greater decrease in potency score compared to patients with lower grade tumors. Conclusion: Interactive ultrasound-guided transperineal

HA/CD44 interactions as potential targets for cancer therapy

Science.gov (United States)

Misra, Suniti; Heldin, Paraskevi; Hascall, Vincent C.; Karamanos, Nikos K.; Skandalis, Spyros S.; Markwald, Roger R.; Ghatak, Shibnath

2011-01-01

It is becoming increasingly clear that signals generated in tumor microenvironments are crucial to tumor cell behavior, such as, survival progression, and metastasis. The establishment of these malignant behaviors requires that tumor cells acquire novel adhesion and migration properties to detach from their original sites for localizing into distant organs. CD44, an adhesion/homing molecule is a major receptor for the glycosaminoglycan hyaluronan, which is one of the major components of the tumor extracellular matrix (ECM). CD44, a multi structural and multifunctional molecule, detects changes in ECM components, and thus is well positioned to provide appropriate responses to changes in the microenvironment, i.e. engagement in cell-cell and cell-ECM interactions, cell traffic, lymph node homing, and presentation of growth factors/cytokines/chemokines to co-ordinate signaling events that enable the cell responses that change in the tissue environment. The potential involvement of CD44variants (CD44v), especially CD44v4-v7 and CD44v6-v9 in tumor progression was confirmed for many tumor types in numerous clinical studies. Down regulation of the standard CD44 isoform (CD44s) in colon cancer is postulated to result in increased tumorigenicity. CD44v-specific functions could be due to their higher binding affinity for hyaluronan than CD44s. Alternatively, CD44v-specific functions could be due to differences in associating molecules, which may bind selectively to the CD44v exon. This review summarizes how the interaction between hyaluronan and CD44v can serve as a potential target for cancer therapy, in particular how silencing the CD44v can target multiple metastatic tumors. PMID:21362138

Role of modern fluorography in the detection of stomach cancer during prophylactic medical examination of the population

International Nuclear Information System (INIS)

Portnoj, L.M.; Turovskij, B.M.; Kaluzhskij, A.A.; Vasil'ev, Yu.D.; Khasidashvili, I.Sh.; Surenchik, V.I.; Simavonyan, K.V.

1986-01-01

Large picture frame fluorography was shown to be promising in the diagnosis of stomach cancer during dispensarization of the population on the basis of over 10000 gastrofluorographic examinations in a specialized unit. Gastrofluorographic units were shown to be one of the optimum organizational forms of performing stomach fluorography. Its advantages (a high informative value, low radiation exposure, etc.) were emphasized. The use of stomach fluorography in persons with a high risk of developing stomach cancer without clear gastric complaints resulted in a significant increase in the number of early diagnosed forms of tumors

Interactive or static reports to guide clinical interpretation of cancer genomics.

Science.gov (United States)

Gray, Stacy W; Gagan, Jeffrey; Cerami, Ethan; Cronin, Angel M; Uno, Hajime; Oliver, Nelly; Lowenstein, Carol; Lederman, Ruth; Revette, Anna; Suarez, Aaron; Lee, Charlotte; Bryan, Jordan; Sholl, Lynette; Van Allen, Eliezer M

2018-05-01

Misinterpretation of complex genomic data presents a major challenge in the implementation of precision oncology. We sought to determine whether interactive genomic reports with embedded clinician education and optimized data visualization improved genomic data interpretation. We conducted a randomized, vignette-based survey study to determine whether exposure to interactive reports for a somatic gene panel, as compared to static reports, improves physicians' genomic comprehension and report-related satisfaction (overall scores calculated across 3 vignettes, range 0-18 and 1-4, respectively, higher score corresponding with improved endpoints). One hundred and five physicians at a tertiary cancer center participated (29% participation rate): 67% medical, 20% pediatric, 7% radiation, and 7% surgical oncology; 37% female. Prior to viewing the case-based vignettes, 34% of the physicians reported difficulty making treatment recommendations based on the standard static report. After vignette/report exposure, physicians' overall comprehension scores did not differ by report type (mean score: interactive 11.6 vs static 10.5, difference = 1.1, 95% CI, -0.3, 2.5, P = .13). However, physicians exposed to the interactive report were more likely to correctly assess sequencing quality (P < .001) and understand when reports needed to be interpreted with caution (eg, low tumor purity; P = .02). Overall satisfaction scores were higher in the interactive group (mean score 2.5 vs 2.1, difference = 0.4, 95% CI, 0.2-0.7, P = .001). Interactive genomic reports may improve physicians' ability to accurately assess genomic data and increase report-related satisfaction. Additional research in users' genomic needs and efforts to integrate interactive reports into electronic health records may facilitate the implementation of precision oncology.

Examination of skin lesions for cancer : Which clinical decision aids and tools are available in general practice?

NARCIS (Netherlands)

Koelink, Cecile J. L.; Jonkman, Marcel F.; Van der Meer, Klaas; Van der Heide, Wouter K.

2014-01-01

Background While skin cancer incidence is rising throughout Europe, general practitioners (GP) feel unsure about their ability to diagnose skin malignancies. Objectives To evaluate whether the GP has sufficient validated clinical decision aids and tools for the examination of potentially malignant

Examining classroom interactions related to difference in students' science achievement

Science.gov (United States)

Zady, Madelon F.; Portes, Pedro R.; Ochs, V. Dan

2003-01-01

The current study examines the cognitive supports that underlie achievement in science by using a cultural historical framework (L. S. Vygotsky (1934/1986), Thought and Language, MIT Press, Cambridge, MA.) and the activity setting (AS) construct (R. G. Tharp & R. Gallimore (1988), Rousing minds to life: Teaching, learning and schooling in social context, Cambridge University Press, Cambridge, MA.) with its five features: personnel, motivations, scripts, task demands, and beliefs. Observations were made of the classrooms of seventh-grade science students, 32 of whom had participated in a prior achievement-related parent-child interaction or home study (P. R. Portes, M. F. Zady, & R. M. Dunham (1998), Journal of Genetic Psychology, 159, 163-178). The results of a quantitative analysis of classroom interaction showed two features of the AS: personnel and scripts. The qualitative field analysis generated four emergent phenomena related to the features of the AS that appeared to influence student opportunity for conceptual development. The emergent phenomenon were science activities, the building of learning, meaning in lessons, and the conflict over control. Lastly, the results of the two-part classroom study were compared to those of the home science AS of high and low achievers. Mismatches in the AS features in the science classroom may constrain the opportunity to learn. Educational implications are discussed.

Radiation factors and smoking interaction at lung cancer incidence for workers at a nuclear enterprise

International Nuclear Information System (INIS)

Tokarskaya, Z.B.; Khokhryakov, V.F.; Okladnikova, N.D.; Belyaeva, Z.D.; Zhuntova, G.V.

1997-01-01

It was shown on the basis of retrospective investigation of 500 workers at a nuclear enterprise (162 cases of lung cancer, 338 persons as matching control) that the interaction of external gamma-irradiation (> 2.0 Gy) and the body - burden of 239 Pu (> 9.3 kBq) at lung cancer is characterized as the multiplicative effect. Combined influence of smoking and radiation factors dependent on smoking index (SI): it changed from additive up to multiplicative and than to antagonistic with the increase of the smoking effect. The received results could be explained on the basis of a two - mutation model of radiation carcinogenesis

Patient education for colon cancer screening: a randomized trial of a video mailed before a physical examination.

Science.gov (United States)

Zapka, Jane G; Lemon, Stephenie C; Puleo, Elaine; Estabrook, Barbara; Luckmann, Roger; Erban, Stephen

2004-11-02

Colorectal cancer screening is underused, and primary care clinicians are challenged to provide patient education within the constraints of busy practices. To test the effect of an educational video, mailed to patients' homes before a physical examination, on performance of colorectal cancer screening, particularly sigmoidoscopy. Randomized, controlled trial. 5 primary care practices in central Massachusetts. 938 patients age 50 to 74 years who were scheduled for an upcoming physical examination, had no personal history of colorectal cancer, and were eligible for lower-endoscopy screening according to current guidelines. Participants were randomly assigned to receive usual care (n = 488) or a video about colorectal cancer, the importance of early detection, and screening options (n = 450). Baseline and 6-month follow-up telephone assessments were conducted. A dependent variable classified screening since baseline as 1) sigmoidoscopy with or without other tests, 2) another test or test combination, or 3) no tests. Overall screening rates were the same in the intervention and control groups (55%). In regression modeling, intervention participants were nonsignificantly more likely to complete sigmoidoscopy alone or in combination with another test (odds ratio, 1.22 [95% CI, 0.88 to 1.70]). Intervention dose (viewing at least half of the video) was significantly related to receiving sigmoidoscopy with or without another test (odds ratio, 2.81 [CI, 1.85 to 4.26]). Recruitment records showed that at least 23% of people coming for periodic health assessments were currently screened by a lower-endoscopy procedure and therefore were not eligible. The primary care sample studied consisted primarily of middle-class white persons who had high screening rates at baseline. The results may not be generalizable to other populations. The trial was conducted during a period of increased health insurance coverage for lower-endoscopy procedures and public media attention to colon

Space-time interactions in childhood cancers

International Nuclear Information System (INIS)

Morris, V.

1990-01-01

During the last twenty five years, there have been sporadic published reports of cases of childhood leukaemia occurring in clusters. Renewed interest in the topic, following suggests that clusters may occur in the vicinity of nuclear establishments, has prompted this report of an investigation into 418 childhood cancer cases which occurred in the Midlands between 1953 and 1960. There was evidence among some age groups and diagnoses of an unexpectedly high number of close pairs of onsets, and some indication of similar patterns among births of children who later developed cancer. Measles appeared to occur more often in the 2-3 years before the onset of leukaemia in children who were later involved in close pairs than in their matched controls. It is concluded that common infectious diseases of childhood may play a minor role in the development of some cancers. Epidemics of these diseases may then be reflected on a greatly reduced scale in the subsequent distribution of cancer cases. (author)

Splicing Factor Prp8 Interacts With NES(AR) and Regulates Androgen Receptor in Prostate Cancer Cells.

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Wang, Dan; Nguyen, Minh M; Masoodi, Khalid Z; Singh, Prabhpreet; Jing, Yifeng; O'Malley, Katherine; Dar, Javid A; Dhir, Rajiv; Wang, Zhou

2015-12-01

Androgen receptor (AR) plays a pivotal role in the development of primary as well as advanced castration-resistant prostate cancer. Previous work in our lab identified a novel nuclear export signal (NES) (NES(AR)) in AR ligand-binding domain essential for AR nucleocytoplasmic trafficking. By characterizing the localization of green fluorescence protein (GFP)-tagged NES(AR), we designed and executed a yeast mutagenesis screen and isolated 7 yeast mutants that failed to display the NES(AR) export function. One of those mutants was identified as the splicing factor pre-mRNA processing factor 8 (Prp8). We further showed that Prp8 could regulate NES(AR) function using short hairpin RNA knockdown of Prp8 coupled with a rapamycin export assay in mammalian cells and knockdown of Prp8 could induce nuclear accumulation of GFP-tagged AR in PC3 cells. Prp8 expression was decreased in castration-resistant LuCaP35 xenograft tumors as compared with androgen-sensitive xenografts. Laser capture microdissection and quantitative PCR showed Prp8 mRNA levels were decreased in human prostate cancer specimens with high Gleason scores. In prostate cancer cells, coimmunoprecipitation and deletion mutagenesis revealed a physical interaction between Prp8 and AR mainly mediated by NES(AR). Luciferase assay with prostate specific antigen promoter-driven reporter demonstrated that Prp8 regulated AR transcription activity in prostate cancer cells. Interestingly, Prp8 knockdown also increased polyubiquitination of endogenous AR. This may be 1 possible mechanism by which it modulates AR activity. These results show that Prp8 is a novel AR cofactor that interacts with NES(AR) and regulates AR function in prostate cancer cells.

A nested case-control approach to interactions between radiation dose and other factors as causes of cancer

Energy Technology Data Exchange (ETDEWEB)

Land, Charles E [Department of Epidemiology, Radiation Epidemiology Branch, US National Cancer Institute, Bethesda, MD (United States)

1992-04-01

Often a nested case-control study is the most practicable approach to estimating the interaction of two cancer risk factors in a large cohort. If one of the factors has already been evaluated for the entire cohort, however, more information is already available about its relationship to risk than could be obtained from a nested study. A modified case-control approach is proposed, in which information about the second, unknown factor is sought for cases and controls matched on the first factor. The approach requires, for interaction models other than the multiplicative, a nonstandard analytical approach incorporating cohort-based information about the first factor. The problem is discussed in the context of breast cancer risk in a defined cohort of female Japanese atomic bomb survivors, in relation to radiation dose and reproductive history. (author)

Colorectal cancer: screening double-contrast barium enema examination in average-risk adults older than 50 years.

Science.gov (United States)

Kung, Justin W; Levine, Marc S; Glick, Seth N; Lakhani, Paras; Rubesin, Stephen E; Laufer, Igor

2006-09-01

To retrospectively determine the diagnostic yield of double-contrast barium enema examinations performed for colorectal cancer screening of neoplasms 1 cm or larger or advanced neoplastic lesions of any size in average-risk adults older than 50 years. The Institutional Review Board at the affiliated Veterans Affairs Medical Center approved this HIPAA-compliant study protocol and did not require informed consent from patients. Computerized databases revealed 276 double-contrast barium enema examinations performed for colorectal cancer screening in average-risk adults older than 50 years. Radiographic and pathologic reports were reviewed to determine the number of patients who had polypoid lesions 1 cm or larger, polyps smaller than 1 cm, or advanced neoplastic lesions of any size. Forty-five (16.3%) of the 276 patients underwent follow-up sigmoidoscopy or colonoscopy. Medical, endoscopic, and pathologic records were reviewed and compared with radiographic findings. The results of double-contrast barium enema examination revealed 74 (26.8%) of 276 patients with 104 polypoid lesions in the colon, including 32 patients (11.6%) with 41 polypoid lesions 1 cm or larger, 15 patients (5.4%) with 19 polyps 6-9 mm, and 27 patients (9.8%) with 44 polyps 5 mm or smaller. Endoscopy was performed in 24 (75%) of 32 patients, the results of which confirmed 23 (72%) of 32 radiographically diagnosed lesions 1 cm or larger in 16 (67%) of 24 patients. In two of these individuals, the polyps were hyperplastic. The remaining 14 patients had a total of 21 neoplastic lesions 1 cm or larger, including 11 tubular adenomas, seven tubulovillous adenomas, one villous adenoma with marked dysplasia, and two cancers. The diagnostic yield of screening double-contrast barium enema examination was 5.1% (14 of 276 patients) for neoplastic lesions 1 cm or larger and 6.2% (17 of 276 patients) for advanced neoplastic lesions of any size. Double-contrast barium enema examinations performed in average

Clinically significant drug–drug interactions involving opioid analgesics used for pain treatment in patients with cancer: a systematic review

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Kotlinska-Lemieszek A

2015-09-01

Full Text Available Aleksandra Kotlinska-Lemieszek,1 Pål Klepstad,2,3,6 Dagny Faksvåg Haugen2,4,5 1Palliative Medicine Chair and Department, University Hospital of the Lord’s Transfiguration, Karol Marcinkowski University of Medical Sciences, Poznan, Poland; 2European Palliative Care Research Centre, Faculty of Medicine, Norwegian University of Science and Technology,Trondheim, Norway; 3Department of Anaesthesiology and Intensive Care Medicine, St Olavs Hospital, Trondheim, Norway; 4Regional Centre of Excellence for Palliative Care, Haukeland University Hospital, Bergen, Norway; 5Department of Clinical Medicine K1, University of Bergen, Bergen, Norway; 6Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway Background: Opioids are the most frequently used drugs to treat pain in cancer patients. In some patients, however, opioids can cause adverse effects and drug–drug interactions. No advice concerning the combination of opioids and other drugs is given in the current European guidelines. Objective: To identify studies that report clinically significant drug–drug interactions involving opioids used for pain treatment in adult cancer patients. Design and data sources: Systematic review with searches in Embase, MEDLINE, and Cochrane Central Register of Controlled Trials from the start of the databases (Embase from 1980 through January 2014. In addition, reference lists of relevant full-text papers were hand-searched. Results: Of 901 retrieved papers, 112 were considered as potentially eligible. After full-text reading, 17 were included in the final analysis, together with 15 papers identified through hand-searching of reference lists. All of the 32 included publications were case reports or case series. Clinical manifestations of drug–drug interactions involving opioids were grouped as follows: 1 sedation and respiratory depression, 2 other central nervous system symptoms, 3 impairment of pain

Evidence of gene-environment interactions between common breast cancer susceptibility loci and established environmental risk factors

DEFF Research Database (Denmark)

Nickels, Stefan; Truong, Thérèse; Hein, Rebecca

2013-01-01

Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cance...

Informal Learning in Academic Student Organizations: An Exploratory Examination of Student-Faculty Interactions and the Relationship to Leadership

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Holzweiss, Peggy C.; Parrott, Kelli Peck; Cole, Bryan R.

2013-01-01

This exploratory study examined informal learning opportunities that exist within student organizations. The researchers specifically isolated academic organizations and the interactions between students and faculty that may occur in this context. Findings indicate that 81% of participants experienced interactions with faculty within the context…

Prognostic and functional role of subtype-specific tumor-stroma interaction in breast cancer.

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Merlino, Giuseppe; Miodini, Patrizia; Callari, Maurizio; D'Aiuto, Francesca; Cappelletti, Vera; Daidone, Maria Grazia

2017-10-01

None of the clinically relevant gene expression signatures available for breast cancer were specifically developed to capture the influence of the microenvironment on tumor cells. Here, we attempted to build subtype-specific signatures derived from an in vitro model reproducing tumor cell modifications after interaction with activated or normal stromal cells. Gene expression signatures derived from HER2+, luminal, and basal breast cancer cell lines (treated by normal fibroblasts or cancer-associated fibroblasts conditioned media) were evaluated in clinical tumors by in silico analysis on published gene expression profiles (GEPs). Patients were classified as microenvironment-positive (μENV+ve), that is, with tumors showing molecular profiles suggesting activation by the stroma, or microenvironment-negative (μENV-ve) based on correlation of their tumors' GEP with the respective subtype-specific signature. Patients with estrogen receptor alpha (ER)+/HER2-/μENV+ve tumors were characterized by 2.5-fold higher risk of developing distant metastases (HR = 2.546; 95% CI: 1.751-3.701, P = 9.84E-07), while μENV status did not affect, or only suggested the risk of distant metastases, in women with HER2+ (HR = 1.541; 95% CI: 0.788-3.012, P = 0.206) or ER-/HER2- tumors (HR = 1.894; 95% CI: 0.938-3.824; P = 0.0747), respectively. In ER+/HER2- tumors, the μENV status remained significantly associated with metastatic progression (HR = 2.098; CI: 1.214-3.624; P = 0.00791) in multivariable analysis including size, age, and Genomic Grade Index. Validity of our in vitro model was also supported by in vitro biological endpoints such as cell growth (MTT assay) and migration/invasion (Transwell assay). In vitro-derived gene signatures tracing the bidirectional interaction with cancer activated fibroblasts are subtype-specific and add independent prognostic information to classical prognostic variables in women with ER+/HER2- tumors. © 2017 The Authors. Published

Breast Self- Examination Contradiction

OpenAIRE

Ayla Akkas Gursoy

2008-01-01

Breast cancer is very important health problem among women in the World and Turkey. Although treatment chance is very rising and survival is getting longer thanks to early diagnosis in breast cancer. Some discussion is making related to breast self examination which is one of the early detection methods in recent years. This article consider the discussions about breast self examination under the historical development light. [TAF Prev Med Bull 2008; 7(3.000): 257-260

Breast Self- Examination Contradiction

Directory of Open Access Journals (Sweden)

Ayla Akkas Gursoy

2008-06-01

Full Text Available Breast cancer is very important health problem among women in the World and Turkey. Although treatment chance is very rising and survival is getting longer thanks to early diagnosis in breast cancer. Some discussion is making related to breast self examination which is one of the early detection methods in recent years. This article consider the discussions about breast self examination under the historical development light. [TAF Prev Med Bull 2008; 7(3.000: 257-260

[Relationship and interaction between folate and expression of methyl-CpG-binding protein 2 in cervical cancerization].

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Li, Q L; Ding, L; Nan, J; Liu, C L; Yang, Z K; Chen, F; Liang, Y L; Wang, J T

2016-07-01

To explore the interaction between folate and the expression of methyl-CpG-binding protein 2(MeCP2)in cervical cancerization. Forty one patients diagnosed with cervical squamous cell carcinoma(SCC), 71 patients diagnosed with cervical intraepithelial neoplasm(CIN1, n=34; CIN2 +, n=37)and 61 women with normal cervix(NC)were recruited in this study. Microbiological assay was conducted to detect the levels of serum folate and RBC folate, Western blot assay and real-time PCR were performed to detect the expression levels of MeCP2 protein and mRNA, respectively. The data were analyzed by Kruskal-Wallis H test, χ(2) test, trend χ(2) test and Spearman correlation with SPSS statistical software(version 20.0), and the interaction were evaluated by using generalized multifactor dimensionality reduction(GMDR)model. The levels of serum folate(H=44.71, Pfolate(H=5.28, Pfolate level and RBC folate level(r=0.270, Pfolate level and the expression level of MeCP2 protein(serum folate: r=-0.226, P=0.003; RBC folate: r=-0.164, P=0.004). Moreover, the results by GMDR model revealed there were interaction among serum folate deficiency, RBC folate deficiency, MeCP2 protein high expression and MeCP2 mRNA high expression in SCC and CIN2 + patients. Folate deficiency and high expression of MeCP2 gene might increase the risk of cervical cancer and its precancerous lesions through interaction among serum folate deficiency, RBC folate deficiency, MeCP2 protein high expression and mRNA high expression in the progression of cervical cancerization.

A 3D printed nano bone matrix for characterization of breast cancer cell and osteoblast interactions

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Zhu, Wei; Castro, Nathan J.; Cui, Haitao; Zhou, Xuan; Boualam, Benchaa; McGrane, Robert; Glazer, Robert I.; Zhang, Lijie Grace

2016-08-01

Bone metastasis is one of the most prevalent complications of late-stage breast cancer, in which the native bone matrix components, including osteoblasts, are intimately involved in tumor progression. The development of a successful in vitro model would greatly facilitate understanding the underlying mechanism of breast cancer bone invasion as well as provide a tool for effective discovery of novel therapeutic strategies. In the current study, we fabricated a series of in vitro bone matrices composed of a polyethylene glycol hydrogel and nanocrystalline hydroxyapatite of varying concentrations to mimic the native bone microenvironment for the investigation of breast cancer bone metastasis. A stereolithography-based three-dimensional (3D) printer was used to fabricate the bone matrices with precisely controlled architecture. The interaction between breast cancer cells and osteoblasts was investigated in the optimized bone matrix. Using a Transwell® system to separate the two cell lines, breast cancer cells inhibited osteoblast proliferation, while osteoblasts stimulated breast cancer cell growth, whereas, both cell lines increased IL-8 secretion. Breast cancer cells co-cultured with osteoblasts within the 3D bone matrix formed multi-cellular spheroids in comparison to two-dimensional monolayers. These findings validate the use of our 3D printed bone matrices as an in vitro metastasis model, and highlights their potential for investigating breast cancer bone metastasis.

Neural protein gamma-synuclein interacting with androgen receptor promotes human prostate cancer progression

International Nuclear Information System (INIS)

Chen, Junyi; Jiao, Li; Xu, Chuanliang; Yu, Yongwei; Zhang, Zhensheng; Chang, Zheng; Deng, Zhen; Sun, Yinghao

2012-01-01

Gamma-synuclein (SNCG) has previously been demonstrated to be significantly correlated with metastatic malignancies; however, in-depth investigation of SNCG in prostate cancer is still lacking. In the present study, we evaluated the role of SNCG in prostate cancer progression and explored the underlying mechanisms. First, alteration of SNCG expression in LNCaP cell line to test the ability of SNCG on cellular properties in vitro and vivo whenever exposing with androgen or not. Subsequently, the Dual-luciferase reporter assays were performed to evaluate whether the role of SNCG in LNCaP is through AR signaling. Last, the association between SNCG and prostate cancer progression was assessed immunohistochemically using a series of human prostate tissues. Silencing SNCG by siRNA in LNCaP cells contributes to the inhibition of cellular proliferation, the induction of cell-cycle arrest at the G1 phase, the suppression of cellular migration and invasion in vitro, as well as the decrease of tumor growth in vivo with the notable exception of castrated mice. Subsequently, mechanistic studies indicated that SNCG is a novel androgen receptor (AR) coactivator. It interacts with AR and promotes prostate cancer cellular growth and proliferation by activating AR transcription in an androgen-dependent manner. Finally, immunohistochemical analysis revealed that SNCG was almost undetectable in benign or androgen-independent tissues prostate lesions. The high expression of SNCG is correlated with peripheral and lymph node invasion. Our data suggest that SNCG may serve as a biomarker for predicting human prostate cancer progression and metastasis. It also may become as a novel target for biomedical therapy in advanced prostate cancer

Antecedent characteristics of online cancer information seeking among rural breast cancer patients: an application of the Cognitive-Social Health Information Processing (C-SHIP) model.

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Shaw, Bret R; Dubenske, Lori L; Han, Jeong Yeob; Cofta-Woerpel, Ludmila; Bush, Nigel; Gustafson, David H; McTavish, Fiona

2008-06-01

Little research has examined the antecedent characteristics of patients most likely to seek online cancer information. This study employs the Cognitive-Social Health Information Processing (C-SHIP) model as a framework to understand what psychosocial characteristics precede online cancer-related information seeking among rural breast cancer patients who often have fewer health care providers and limited local support services. Examining 144 patients who were provided free computer hardware, Internet access, and training for how to use an interactive cancer communication system, pretest survey scores indicating patients' psychosocial status were correlated with specific online cancer information seeking behaviors. Each of the factors specified by the C-SHIP model had significant relationships with online cancer information seeking behaviors, with the strongest findings emerging for cancer-relevant encodings and self-construals, cancer-relevant beliefs and expectancies, and cancer-relevant self-regulatory competencies and skills. Specifically, patients with more negative appraisals in these domains were more likely to seek out online cancer information. Additionally, antecedent variables associated with the C-SHIP model had more frequent relationships with experiential information as compared with to didactic information. This study supports the applicability of the model to discern why people afflicted with cancer may seek online information to cope with their disease.

Antecedent Characteristics of Online Cancer Information Seeking Among Rural Breast Cancer Patients: An Application of the Cognitive-Social Health Information Processing (C-SHIP) Model

Science.gov (United States)

Shaw, Bret R.; DuBenske, Lori L.; Han, Jeong Yeob; Cofta-Woerpel, Ludmila; Bush, Nigel; Gustafson, David H.; McTavish, Fiona

2013-01-01

Little research has examined the antecedent characteristics of patients most likely to seek online cancer information. This study employs the Cognitive-Social Health Information Processing (C-SHIP) model as a framework to understand what psychosocial characteristics precede online cancer-related information seeking among rural breast cancer patients who often have fewer healthcare providers and limited local support services. Examining 144 patients who were provided free computer hardware, Internet access and training for how to use an Interactive Cancer Communication System, pre-test survey scores indicating patients’ psychosocial status were correlated with specific online cancer information seeking behaviors. Each of the factors specified by the C-SHIP model had significant relationships with online cancer information seeking behaviors with the strongest findings emerging for cancer-relevant encodings and self-construals, cancer-relevant beliefs and expectancies and cancer-relevant self-regulatory competencies and skills. Specifically, patients with more negative appraisals in these domains were more likely to seek out online cancer information. Additionally, antecedent variables associated with the C-SHIP model had more frequent relationships with experiential information as compared to didactic information. This study supports the applicability of the model to discern why people afflicted with cancer may seek online information to cope with their disease. PMID:18569368

GAIP interacting protein C-terminus regulates autophagy and exosome biogenesis of pancreatic cancer through metabolic pathways.

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Santanu Bhattacharya

Full Text Available GAIP interacting protein C terminus (GIPC is known to play an important role in a variety of physiological and disease states. In the present study, we have identified a novel role for GIPC as a master regulator of autophagy and the exocytotic pathways in cancer. We show that depletion of GIPC-induced autophagy in pancreatic cancer cells, as evident from the upregulation of the autophagy marker LC3II. We further report that GIPC regulates cellular trafficking pathways by modulating the secretion, biogenesis, and molecular composition of exosomes. We also identified the involvement of GIPC on metabolic stress pathways regulating autophagy and microvesicular shedding, and observed that GIPC status determines the loading of cellular cargo in the exosome. Furthermore, we have shown the overexpression of the drug resistance gene ABCG2 in exosomes from GIPC-depleted pancreatic cancer cells. We also demonstrated that depletion of GIPC from cancer cells sensitized them to gemcitabine treatment, an avenue that can be explored as a potential therapeutic strategy to overcome drug resistance in cancer.

The Interactions between Insulin and Androgens in Progression to Castrate-Resistant Prostate Cancer

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Jennifer H. Gunter

2012-01-01

Full Text Available An association between the metabolic syndrome and reduced testosterone levels has been identified, and a specific inverse relationship between insulin and testosterone levels suggests that an important metabolic crosstalk exists between these two hormonal axes; however, the mechanisms by which insulin and androgens may be reciprocally regulated are not well described. Androgen-dependant gene pathways regulate the growth and maintenance of both normal and malignant prostate tissue, and androgen-deprivation therapy (ADT in patients exploits this dependence when used to treat recurrent and metastatic prostate cancer resulting in tumour regression. A major systemic side effect of ADT includes induction of key features of the metabolic syndrome and the consistent feature of hyperinsulinaemia. Recent studies have specifically identified a correlation between elevated insulin and high-grade PCa and more rapid progression to castrate resistant disease. This paper examines the relationship between insulin and androgens in the context of prostate cancer progression. Prostate cancer patients present a promising cohort for the exploration of insulin stabilising agents as adjunct treatments for hormone deprivation or enhancers of chemosensitivity for treatment of advanced prostate cancer.

The Interactions between Insulin and Androgens in Progression to Castrate-Resistant Prostate Cancer

Science.gov (United States)

Gunter, Jennifer H.; Lubik, Amy A.; McKenzie, Ian; Pollak, Michael; Nelson, Colleen C.

2012-01-01

An association between the metabolic syndrome and reduced testosterone levels has been identified, and a specific inverse relationship between insulin and testosterone levels suggests that an important metabolic crosstalk exists between these two hormonal axes; however, the mechanisms by which insulin and androgens may be reciprocally regulated are not well described. Androgen-dependant gene pathways regulate the growth and maintenance of both normal and malignant prostate tissue, and androgen-deprivation therapy (ADT) in patients exploits this dependence when used to treat recurrent and metastatic prostate cancer resulting in tumour regression. A major systemic side effect of ADT includes induction of key features of the metabolic syndrome and the consistent feature of hyperinsulinaemia. Recent studies have specifically identified a correlation between elevated insulin and high-grade PCa and more rapid progression to castrate resistant disease. This paper examines the relationship between insulin and androgens in the context of prostate cancer progression. Prostate cancer patients present a promising cohort for the exploration of insulin stabilising agents as adjunct treatments for hormone deprivation or enhancers of chemosensitivity for treatment of advanced prostate cancer. PMID:22548055

Autoimmune response to PARP and BRCA1/BRCA2 in cancer

Science.gov (United States)

Zhu, Qing; Han, Su-Xia; Zhou, Cong-Ya; Cai, Meng-Jiao; Dai, Li-Ping; Zhang, Jian-Ying

2015-01-01

Purpose To determine the role of autoantibodies to PARP1 and BRCA1/BRCA2 which were involved in the synthetic lethal interaction in cancer. Methods Enzyme-Linked Immunosorbent Assay (ELISA) was used to detect autoantibodies to PARP1 and BRCA1/BRCA2 in 618 serum samples including 131 from breast cancer, 94 from lung cancer, 34 from ovarian cancer, 107 from prostate cancer, 76 from liver cancer, 41 from pancreatic cancer and 135 from normal individuals. The positive sera with ELISA were confirmed by Western blot. Immunohistochemistry was used to examine the expression of PARP1 and BRCA1/BRCA2 in breast cancer. Results Autoantibody frequency to PARP1, BRCA1, and BRCA2 in cancer varied from 0% to 50%. When the sera from cancer patients were tested for the presence of autoantibodies to PARP1 and BRCA1/BRCA2, the autoantibody responses slightly decreased and the positive autoantibody reactions varied from 0% to 50.0%. This was significantly higher autoantibody responses to PARP1 and BRCA1/BRCA2 (especially to PARP1 and BRCA1) in ovarian cancer and breast cancer compared to normal control sera (P cancer was different (P cancers have different profiles of autoantibodies. The autoantibodies to proteins involving the synthetic lethal interactions would be novel serological biomarker in some selective cancers. PMID:25865228

Breast Cancer Knowledge, Perception and Breast Self- Examination Practices among Yemeni Women: an Application of the Health Belief Model.

Science.gov (United States)

Al-Sakkaf, Khaled Abdulla; Basaleem, Huda Omer

2016-01-01

The incidence of breast cancer is rapidly increasing in Yemen with recent indications of constituting one-third of female cancers. The main problem in Yemen remains very late presentation of breast cancer, most of which should have been easily recognisable. Since stage of disease at diagnosis is the most important prognostic variable, early diagnosis is an important option to be considered for control of breast cancer in low resourced settings like Yemen. In the present study, we aimed at describing breast cancer knowledge, perceptions and breast self-examination (BSE) practices among a sample of Yemeni women. This cross-sectional study covered 400 women attending four reproductive health centres in Aden, Yemen through face-to-face interview using a structured questionnaire during April - July 2014. We collected data on sociodemographic characteristics, knowledge about breast cancer, and screening practices as well as respondents' perceptions based on the five sub scales of the Health Belief Model (HBM): perceived susceptibility; perceived severity; perceived barriers; perceived benefits; and self-efficacy. The response format was a fivepoint Likert scale. Statistical Package for Social Sciences (SPSS 20) was used for statistical analysis. Statistical significance was set at pearly detection and reduce the burden of breast cancer.

A Preliminary Examination of the Relationship Between Social Networking Interactions, Internet Use, and Thwarted Belongingness.

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Moberg, Fallon B; Anestis, Michael D

2015-01-01

Joiner's (2005) interpersonal-psychological theory of suicide hypothesizes that suicidal desire develops in response to the joint presence of thwarted belongingness and perceived burdensomeness. To consider the potential influence of online interactions and behaviors on these outcomes. To address this, we administered an online protocol assessing suicidal desire and online interactions in a sample of 305 undergraduates (83.6% female). We hypothesized negative interactions on social networking sites and a preference for online social interactions would be associated with thwarted belongingness. We also conducted an exploratory analysis examining the associations between Internet usage and perceived burdensomeness. Higher levels of negative interactions on social networking sites, but no other variables, significantly predicted thwarted belongingness. Our exploratory analysis showed that none of our predictors were associated with perceived burdensomeness after accounting for demographics, depression, and thwarted belongingness. Our findings indicate that a general tendency to have negative interactions on social networking sites could possibly impact suicidal desire and that these effects are significant above and beyond depression symptoms. Furthermore, no other aspect of problematic Internet use significantly predicted our outcomes in multivariate analyses, indicating that social networking in particular may have a robust effect on thwarted belongingness.

BAG3 promotes stem cell-like phenotype in breast cancer by upregulation of CXCR4 via interaction with its transcript.

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Liu, Bao-Qin; Zhang, Song; Li, Si; An, Ming-Xin; Li, Chao; Yan, Jing; Wang, Jia-Mei; Wang, Hua-Qin

2017-07-13

BAG3 is an evolutionarily conserved co-chaperone expressed at high levels and has a prosurvival role in many tumor types. The current study reported that BAG3 was induced under specific floating culture conditions that enrich breast cancer stem cell (BCSC)-like cells in spheres. Ectopic BAG3 overexpression increased CD44 + /CD24 - CSC subpopulations, first-generation and second-generation mammosphere formation, indicating that BAG3 promotes CSC self-renewal and maintenance in breast cancer. We further demonstrated that mechanically, BAG3 upregulated CXCR4 expression at the post-transcriptional level. Further studies showed that BAG3 interacted with CXCR4 mRNA and promoted its expression via its coding and 3'-untranslational regions. BAG3 was also found to be positively correlated with CXCR4 expression and unfavorable prognosis in patients with breast cancer. Taken together, our data demonstrate that BAG3 promotes BCSC-like phenotype through CXCR4 via interaction with its transcript. Therefore, this study establishes BAG3 as a potential adverse prognostic factor and a therapeutic target of breast cancer.

Quality of life and mental health among women with ovarian cancer: examining the role of emotional and instrumental social support seeking.

Science.gov (United States)

Hill, Erin M

2016-07-01

The purpose of the present study was to examine the role of emotional and instrumental social support seeking in the quality of life (QOL) and mental health of women with ovarian cancer. Participants were recruited through the Pennsylvania Cancer Registry, and one hundred women took part in a mail questionnaire that collected information on their demographics, medical status, social support seeking, QOL and mental health including anxiety, depression and stress. Hierarchical linear regression analyses were conducted to assess the influence of emotional and instrumental social support seeking on QOL and mental health. After controlling for remission status, greater emotional social support seeking was predictive of higher overall QOL, social/family QOL, functional QOL and lower depression scores. Instrumental social support seeking was not significant in the models. The results illustrate that social support seeking as a coping mechanism is an important consideration in the QOL and mental health of women with ovarian cancer. Future studies should examine the psychological and behavioral mediators of the relationship to further understand the QOL and mental health of women with ovarian cancer.

Returning to School After Adolescent Cancer: A Qualitative Examination of Australian Survivors' and Their Families' Perspectives.

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McLoone, Jordana K; Wakefield, Claire E; Butow, Phyllis; Fleming, Catharine; Cohn, Richard J

2011-06-01

To examine key factors related to adolescent cancer survivors' return to school after cancer treatment completion, which can be a time of complex transition. Seventy semi-structured interviews were conducted with 19 adolescent cancer survivors (mean age 16.1 years), 21 mothers, 15 fathers, and 15 siblings from 22 Australian families. The conceptual framework of Miles and Huberman (1994) was employed to analyze interview data and emergent themes were organized using the software package QSR NVivo 8.0. Barriers to successful school re-entry included symptoms of fatigue, anxiety (particularly regarding examinations), and poor communication between families and the broader school community. Changing grade or school typically extinguished pre-existing support networks and was perceived by parents as a period of unmet need. Support from friends, teachers, tutors, and the hospital outreach nurse were seen as instrumental in creating a positive school re-entry experience. However, the majority of participants reported that support from the school counselor was minimal. Siblings reported this period as relatively non-impactful regarding their own education. Additional support is needed to help parents navigate the education system and to advocate effectively for their child's academic needs beyond the immediate re-entry period. There is strong potential for school counselors to increase the level of support they provide adolescents and their parents during the school re-entry period. The impact of this period on siblings' education is under-studied and warrants further research.

An epistatic interaction between the PAX8 and STK17B genes in papillary thyroid cancer susceptibility.

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Iñigo Landa

Full Text Available Papillary Thyroid Cancer (PTC is a heterogeneous and complex disease; susceptibility to PTC is influenced by the joint effects of multiple common, low-penetrance genes, although relatively few have been identified to date. Here we applied a rigorous combined approach to assess both the individual and epistatic contributions of genetic factors to PTC susceptibility, based on one of the largest series of thyroid cancer cases described to date. In addition to identifying the involvement of TSHR variation in classic PTC, our pioneer study of epistasis revealed a significant interaction between variants in STK17B and PAX8. The interaction was detected by MD-MBR (p = 0.00010 and confirmed by other methods, and then replicated in a second independent series of patients (MD-MBR p = 0.017. Furthermore, we demonstrated an inverse correlation between expression of PAX8 and STK17B in a set of cell lines derived from human thyroid carcinomas. Overall, our work sheds additional light on the genetic basis of thyroid cancer susceptibility, and suggests a new direction for the exploration of the inherited genetic contribution to disease using association studies.

The Changes of Energy Interactions between Nucleus Function and Mitochondria Functions Causing Transmutation of Chronic Inflammation into Cancer Metabolism.

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Ponizovskiy, Michail R

2016-01-01

Interactions between nucleus and mitochondria functions induce the mechanism of maintenance stability of cellular internal energy according to the first law of thermodynamics in able-bodied cells and changes the mechanisms of maintenance stability of cellular internal energy creating a transition stationary state of ablebodied cells into quasi-stationary pathologic states of acute inflammation transiting then into chronic inflammation and then transmuting into cancer metabolism. The mechanisms' influences of intruding etiologic pathologic agents (microbe, virus, etc.) lead to these changes of energy interactions between nucleus and mitochondria functions causing general acute inflammation, then passing into local chronic inflammation, and reversing into cancer metabolism transmutation. Interactions between biochemical processes and biophysical processes of cellular capacitors' operations create a supplementary mechanism of maintenance stability of cellular internal energy in the norm and in pathology. Discussion of some scientific works eliminates doubts of the authors of these works.

Real-time Raman spectroscopy for in vivo, online gastric cancer diagnosis during clinical endoscopic examination.

Science.gov (United States)

Duraipandian, Shiyamala; Sylvest Bergholt, Mads; Zheng, Wei; Yu Ho, Khek; Teh, Ming; Guan Yeoh, Khay; Bok Yan So, Jimmy; Shabbir, Asim; Huang, Zhiwei

2012-08-01

Optical spectroscopic techniques including reflectance, fluorescence and Raman spectroscopy have shown promising potential for in vivo precancer and cancer diagnostics in a variety of organs. However, data-analysis has mostly been limited to post-processing and off-line algorithm development. In this work, we develop a fully automated on-line Raman spectral diagnostics framework integrated with a multimodal image-guided Raman technique for real-time in vivo cancer detection at endoscopy. A total of 2748 in vivo gastric tissue spectra (2465 normal and 283 cancer) were acquired from 305 patients recruited to construct a spectral database for diagnostic algorithms development. The novel diagnostic scheme developed implements on-line preprocessing, outlier detection based on principal component analysis statistics (i.e., Hotelling's T2 and Q-residuals) for tissue Raman spectra verification as well as for organ specific probabilistic diagnostics using different diagnostic algorithms. Free-running optical diagnosis and processing time of < 0.5 s can be achieved, which is critical to realizing real-time in vivo tissue diagnostics during clinical endoscopic examination. The optimized partial least squares-discriminant analysis (PLS-DA) models based on the randomly resampled training database (80% for learning and 20% for testing) provide the diagnostic accuracy of 85.6% [95% confidence interval (CI): 82.9% to 88.2%] [sensitivity of 80.5% (95% CI: 71.4% to 89.6%) and specificity of 86.2% (95% CI: 83.6% to 88.7%)] for the detection of gastric cancer. The PLS-DA algorithms are further applied prospectively on 10 gastric patients at gastroscopy, achieving the predictive accuracy of 80.0% (60/75) [sensitivity of 90.0% (27/30) and specificity of 73.3% (33/45)] for in vivo diagnosis of gastric cancer. The receiver operating characteristics curves further confirmed the efficacy of Raman endoscopy together with PLS-DA algorithms for in vivo prospective diagnosis of gastric cancer

Interval lung cancer after a negative CT screening examination: CT findings and outcomes in National Lung Screening Trial participants

International Nuclear Information System (INIS)

Gierada, David S.; Pinsky, Paul F.; Duan, Fenghai; Garg, Kavita; Hart, Eric M.; Kazerooni, Ella A.; Nath, Hrudaya; Watts, Jubal R.; Aberle, Denise R.

2017-01-01

This study retrospectively analyses the screening CT examinations and outcomes of the National Lung Screening Trial (NLST) participants who had interval lung cancer diagnosed within 1 year after a negative CT screen and before the next annual screen. The screening CTs of all 44 participants diagnosed with interval lung cancer (cases) were matched with negative CT screens of participants who did not develop lung cancer (controls). A majority consensus process was used to classify each CT screen as positive or negative according to the NLST criteria and to estimate the likelihood that any abnormalities detected retrospectively were due to lung cancer. By retrospective review, 40/44 cases (91%) and 17/44 controls (39%) met the NLST criteria for a positive screen (P < 0.001). Cases had higher estimated likelihood of lung cancer (P < 0.001). Abnormalities included pulmonary nodules ≥4 mm (n = 16), mediastinal (n = 8) and hilar (n = 6) masses, and bronchial lesions (n = 6). Cancers were stage III or IV at diagnosis in 32/44 cases (73%); 37/44 patients (84%) died of lung cancer, compared to 225/649 (35%) for all screen-detected cancers (P < 0.0001). Most cases met the NLST criteria for a positive screen. Awareness of missed abnormalities and interpretation errors may aid lung cancer identification in CT screening. (orig.)

Interval lung cancer after a negative CT screening examination: CT findings and outcomes in National Lung Screening Trial participants

Energy Technology Data Exchange (ETDEWEB)

Gierada, David S. [Washington University School of Medicine, Mallinckrodt Institute of Radiology, Box 8131, St. Louis, MO (United States); Pinsky, Paul F. [National Cancer Institute, Bethesda, MD (United States); Duan, Fenghai [Brown University School of Public Health, Department of Biostatistics and Center for Statistical Sciences, Providence, RI (United States); Garg, Kavita [University of Colorado School of Medicine, Mail Stop F726, Box 6510, Aurora, CO (United States); Hart, Eric M. [Northwestern University, Feinberg School of Medicine, Department of Radiology, Chicago, IL (United States); Kazerooni, Ella A. [University of Michigan Health System, Department of Radiology, Ann Arbor, MI (United States); Nath, Hrudaya; Watts, Jubal R. [University of Alabama at Birmingham School of Medicine, Department of Radiology-JTN370, Birmingham, AL (United States); Aberle, Denise R. [David Geffen School of Medicine at UCLA, Department of Radiological Sciences, Los Angeles, CA (United States)

2017-08-15

This study retrospectively analyses the screening CT examinations and outcomes of the National Lung Screening Trial (NLST) participants who had interval lung cancer diagnosed within 1 year after a negative CT screen and before the next annual screen. The screening CTs of all 44 participants diagnosed with interval lung cancer (cases) were matched with negative CT screens of participants who did not develop lung cancer (controls). A majority consensus process was used to classify each CT screen as positive or negative according to the NLST criteria and to estimate the likelihood that any abnormalities detected retrospectively were due to lung cancer. By retrospective review, 40/44 cases (91%) and 17/44 controls (39%) met the NLST criteria for a positive screen (P < 0.001). Cases had higher estimated likelihood of lung cancer (P < 0.001). Abnormalities included pulmonary nodules ≥4 mm (n = 16), mediastinal (n = 8) and hilar (n = 6) masses, and bronchial lesions (n = 6). Cancers were stage III or IV at diagnosis in 32/44 cases (73%); 37/44 patients (84%) died of lung cancer, compared to 225/649 (35%) for all screen-detected cancers (P < 0.0001). Most cases met the NLST criteria for a positive screen. Awareness of missed abnormalities and interpretation errors may aid lung cancer identification in CT screening. (orig.)

Theory of Planned Behavior in the Classroom: An Examination of the Instructor Confirmation-Interaction Model

Science.gov (United States)

Burns, Michael E.; Houser, Marian L.; Farris, Kristen LeBlanc

2018-01-01

The current study utilizes the theory of planned behavior (Ajzen "Organizational Behavior and Human Decision Processes," 50, 179-211 Ajzen 1991) to examine an instructor confirmation-interaction model in the instructional communication context to discover a means by which instructors might cultivate positive student attitudes and…

Women and Cancer: Examining Breast Cancer-Screening Behaviors and Survival

Centers for Disease Control (CDC) Podcasts

This podcast features Siran Koroukian, PhD, associate professor in the School of Medicine at Case Western Reserve University and lead author of one of PCD’s most recent articles. Dr. Koroukian answers questions about the National Breast and Cervical Cancer Early Detection Program (BCCP) in Ohio and discusses the effectiveness of the program among low-income women enrolled Medicare.

Communication in cancer care: psycho-social, interactional, and cultural issues. A general overview and the example of India

OpenAIRE

Chaturvedi, Santosh K.; Strohschein, Fay J.; Saraf, Gayatri; Loiselle, Carmen G.

2014-01-01

Communication is a core aspect of psycho-oncology care. This article examines key psychosocial, cultural, and technological factors that affect this communication. Drawing from advances in clinical work and accumulating bodies of empirical evidence, the authors identify determining factors for high quality, efficient, and sensitive communication and support for those affected by cancer. Cancer care in India is highlighted as a salient example. Cultural factors affecting cancer communication i...

Advances and advantages of nanomedicine in the pharmacological targeting of hyaluronan-CD44 interactions and signaling in cancer.

Science.gov (United States)

Skandalis, Spyros S; Gialeli, Chrisostomi; Theocharis, Achilleas D; Karamanos, Nikos K

2014-01-01

Extensive experimental evidence in cell and animal tumor models show that hyaluronan-CD44 interactions are crucial in both malignancy and resistance to cancer therapy. Because of the intimate relationship between the hyaluronan-CD44 system and tumor cell survival and growth, it is an increasingly investigated area for applications to anticancer chemotherapeutics. Interference with the hyaluronan-CD44 interaction by targeting drugs to CD44, targeting drugs to the hyaluronan matrix, or interfering with hyaluronan matrix/tumor cell-associated CD44 interactions is a viable strategy for cancer treatment. Many of these methods can decrease tumor burden in animal models but have yet to show significant clinical utility. Recent advances in nanomedicine have offered new valuable tools for cancer detection, prevention, and treatment. The enhanced permeability and retention effect has served as key rationale for using nanoparticles to treat solid tumors. However, the targeted and uniform delivery of these particles to all regions of tumors in sufficient quantities requires optimization. An ideal nanocarrier should be equipped with selective ligands that are highly or exclusively expressed on target cells and thus endow the carriers with specific targeting capabilities. In this review, we describe how the hyaluronan-CD44 system may provide such an alternative in tumors expressing specific CD44 variants. © 2014 Elsevier Inc. All rights reserved.

Psychological distress and breast self-examination frequency in women at increased risk for hereditary or familial breast cancer

NARCIS (Netherlands)

van Dooren, S.; Rijnsburger, A. J.; Seynaeve, C.; Kriege, A.; Duivenvoorden, H. J.; Bartels, C. C. M.; Essink-Bot, M. L.; de Koning, H. J.; Tibben, A.

2003-01-01

BACKGROUND: The Magnetic Resonance Imaging Screening study evaluates the efficacy and psychological impact of a surveillance program for women at increased risk for hereditary or familial breast cancer in the Netherlands. Surveillance consists of biannual physical examination, annual mammography,

Interaction between polymorphisms in aspirin metabolic pathways, regular aspirin use and colorectal cancer risk: A case-control study in unselected white European populations.

Directory of Open Access Journals (Sweden)

Harsh Sheth

Full Text Available Regular aspirin use is associated with reduced risk of colorectal cancer (CRC. Variation in aspirin's chemoprevention efficacy has been attributed to the presence of single nucleotide polymorphisms (SNPs. We conducted a meta-analysis using two large population-based case-control datasets, the UK-Leeds Colorectal Cancer Study Group and the NIH-Colon Cancer Family Registry, having a combined total of 3325 cases and 2262 controls. The aim was to assess 42 candidate SNPs in 15 genes whose association with colorectal cancer risk was putatively modified by aspirin use, in the literature. Log odds ratios (ORs and standard errors were estimated for each dataset separately using logistic regression adjusting for age, sex and study site, and dataset-specific results were combined using random effects meta-analysis. Meta-analysis showed association between SNPs rs6983267, rs11694911 and rs2302615 with CRC risk reduction (All P<0.05. Association for SNP rs6983267 in the CCAT2 gene only was noteworthy after multiple test correction (P = 0.001. Site-specific analysis showed association between SNPs rs1799853 and rs2302615 with reduced colon cancer risk only (P = 0.01 and P = 0.004, respectively, however neither reached significance threshold following multiple test correction. Meta-analysis of SNPs rs2070959 and rs1105879 in UGT1A6 gene showed interaction between aspirin use and CRC risk (Pinteraction = 0.01 and 0.02, respectively; stratification by aspirin use showed an association for decreased CRC risk for aspirin users having a wild-type genotype (rs2070959 OR = 0.77, 95% CI = 0.68-0.86; rs1105879 OR = 0.77 95% CI = 0.69-0.86 compared to variant allele cariers. The direction of the interaction however is in contrast to that published in studies on colorectal adenomas. Both SNPs showed potential site-specific interaction with aspirin use and colon cancer risk only (Pinteraction = 0.006 and 0.008, respectively, with the direction of association similar to

Determination of doses and cancer risk to patients undergoing digital x-ray examinations at the Tamale Teaching Hospital

International Nuclear Information System (INIS)

Aweligiba, S.A.

2015-07-01

Entrance surface and effective doses as well as cancer risk to patients for three common radiological examinations were estimated at the radiology department of the Tamale Teaching Hospital. The quality control assessment indicated that the digital x-ray equipment used, performed self-consistently in line with acceptable performance criteria. The study included eighty-two (82) adult patients undergoing three x-ray imaging modalities; Chest, Abdomen and Pelvis Examinations. From the study the mean entrance dose to abdomen and pelvis were found to be 0.6 ± 0.2 mGy whiles that of chest was found to be 0.2 ± 0.1 mGy. These were found to be lower than results of studies carried out elsewhere. The effective dose to patient was computed using PCXMC 2.0 software. The results shows an average effective dose of 0.036 mSv, 0.084 mSv and 0.067 mSv for chest, abdomen and pelvis examinations respectively. The risk of radiation induced cancer as a result to entrance surface dose was found to be 5.68 x 10-5 %, 1.58 x 10-4 % and 1.49 x 10-4 % for Chest, Abdomen and Pelvis examinations respectively. The third quartile values of the entrance surface dose were found to be lower than recommended diagnostic reference levels published by NRPB, UK and the IAEA for the examinations under study. (author)

Genotoxicity studies on DNA-interactive telomerase inhibitors with application as anti-cancer agents.

Science.gov (United States)

Harrington, Dean J; Cemeli, Eduardo; Carder, Joanna; Fearnley, Jamie; Estdale, Sian; Perry, Philip J; Jenkins, Terence C; Anderson, Diana

2003-01-01

Telomerase-targeted strategies have aroused recent interest in anti-cancer chemotherapy, because DNA-binding drugs can interact with high-order tetraplex rather than double-stranded (duplex) DNA targets in tumour cells. However, the protracted cell-drug exposure times necessary for clinical application require that telomerase inhibitory efficacy must be accompanied by both low inherent cytotoxicity and the absence of mutagenicity/genotoxicity. For the first time, the genotoxicity of a number of structurally diverse DNA-interactive telomerase inhibitors is examined in the Ames test using six Salmonella typhimurium bacterial strains (TA1535, TA1537, TA1538, TA98, TA100, and TA102). DNA damage induced by each agent was also assessed using the Comet assay with human lymphocytes. The two assay procedures revealed markedly different genotoxicity profiles that are likely to reflect differences in metabolism and/or DNA repair between bacterial and mammalian cells. The mutational spectrum for a biologically active fluorenone derivative, shown to be mutagenic in the TA100 strain, was characterised using a novel and rapid assay method based upon PCR amplification of a fragment of the hisG46 allele, followed by RFLP analysis. Preliminary analysis indicates that the majority (84%) of mutations induced by this compound are C --> A transversions at position 2 of the missense proline codon of the hisG46 allele. However, despite its genotoxic bacterial profile, this fluorenone agent gave a negative response in the Comet assay, and demonstrates how unwanted systemic effects (e.g., cytotoxicity and genotoxicity) can be prevented or ameliorated through suitable molecular fine-tuning of a candidate drug in targeted human tumour cells. Copyright 2003 Wiley-Liss, Inc.

Interaction between polymorphisms in aspirin metabolic pathways, regular aspirin use and colorectal cancer risk: A case-control study in unselected white European populations.

Science.gov (United States)

Sheth, Harsh; Northwood, Emma; Ulrich, Cornelia M; Scherer, Dominique; Elliott, Faye; Barrett, Jennifer H; Forman, David; Wolf, C Roland; Smith, Gillian; Jackson, Michael S; Santibanez-Koref, Mauro; Haile, Robert; Casey, Graham; Jenkins, Mark; Win, Aung Ko; Hopper, John L; Marchand, Loic Le; Lindor, Noralane M; Thibodeau, Stephen N; Potter, John D; Burn, John; Bishop, D Timothy

2018-01-01

Regular aspirin use is associated with reduced risk of colorectal cancer (CRC). Variation in aspirin's chemoprevention efficacy has been attributed to the presence of single nucleotide polymorphisms (SNPs). We conducted a meta-analysis using two large population-based case-control datasets, the UK-Leeds Colorectal Cancer Study Group and the NIH-Colon Cancer Family Registry, having a combined total of 3325 cases and 2262 controls. The aim was to assess 42 candidate SNPs in 15 genes whose association with colorectal cancer risk was putatively modified by aspirin use, in the literature. Log odds ratios (ORs) and standard errors were estimated for each dataset separately using logistic regression adjusting for age, sex and study site, and dataset-specific results were combined using random effects meta-analysis. Meta-analysis showed association between SNPs rs6983267, rs11694911 and rs2302615 with CRC risk reduction (All Paspirin use and CRC risk (Pinteraction = 0.01 and 0.02, respectively); stratification by aspirin use showed an association for decreased CRC risk for aspirin users having a wild-type genotype (rs2070959 OR = 0.77, 95% CI = 0.68-0.86; rs1105879 OR = 0.77 95% CI = 0.69-0.86) compared to variant allele cariers. The direction of the interaction however is in contrast to that published in studies on colorectal adenomas. Both SNPs showed potential site-specific interaction with aspirin use and colon cancer risk only (Pinteraction = 0.006 and 0.008, respectively), with the direction of association similar to that observed for CRC. Additionally, they showed interaction between any non-steroidal anti-inflammatory drugs (including aspirin) use and CRC risk (Pinteraction = 0.01 for both). All gene x environment (GxE) interactions however were not significant after multiple test correction. Candidate gene investigation indicated no evidence of GxE interaction between genetic variants in genes involved in aspirin pathways, regular aspirin use and colorectal cancer

Differential mental health impact of cancer across racial/ethnic groups: findings from a population-based study in California.

Science.gov (United States)

Alcalá, Héctor E

2014-09-08

Little research has examined the interactive effect of cancer status and race/ethnicity on mental health. As such, the present study examined the mental health of adults, 18 and over, diagnosed with cancer. This study examined the extent to which a cancer diagnosis is related to poorer mental health because it erodes finances and the extent to which the mental health impact of cancer differs across racial/ethnic groups. Furthermore, this study aimed to test the stress process model, which posits that the proliferation of stress can lead to mental illness and this process can differ across racial/ethnic groups. Data from the 2005 Adult California Health Interview Survey was used (N = 42,879). The Kessler 6, a validated measure of psychological distress, was used to measure mental health, with higher scores suggesting poorer mental health. Scores on the Kessler 6 ranged from 0 to 24. Linear regression models estimating psychological distress tested each aim. The mediating effect of income and the race by cancer interaction were tested. After controlling for gender, age, insurance status, education and race/ethnicity, cancer was associated with higher Kessler 6 scores. About 6% of this effect was mediated by household income (t = 4.547; SE = 0.011; p groups. Future work should explore reasons for these disparities. Efforts to increase access to mental health services among minorities with cancer are needed.

Trends in botanical dietary supplement use among US adults by cancer status: The National Health and Nutrition Examination Survey, 1999 to 2014.

Science.gov (United States)

Li, Chao; Hansen, Richard A; Chou, Chiahung; Calderón, Angela I; Qian, Jingjing

2018-03-15

Patients with cancer may use botanical dietary supplements (BDS) in an attempt to manage the side effects of chemotherapy, yet evidence about BDS use among patients with cancer is limited. The authors examined trends in BDS use among US adults according to cancer status and patient characteristics. A serial, cross-sectional study was conducted using data from the National Health and Nutrition Examination Survey from 1999 through 2014 (n = 43,644). Self-reported cancer diagnosis history and any BDS use in the preceding 30 days were determined. The prevalence of BDS use was calculated in each cycle for respondents with and without cancer, both overall and by patient characteristics. Simple linear regression models were applied to test for trends in BDS use at a 2-sided P value < .05. Multiple logistic regression models were performed to identify the patient factors associated with BDS use. The results were weighted to represent national estimates. The prevalence of BDS use was greater among participants who had cancer compared with participants who did not have cancer, but trends remained stable during 1999 through 2014 for both groups. Trends in BDS use declined in patients with cancer who were older (P trend  = .047), had a low annual family income (P trend  = .028), and had a lower education level (P trend  = .004). Among the respondents without cancer, trends in BDS use declined in those who were middle-aged (P trend  = .025), non-Hispanic whites (P trend  = .025), those with a lower education level (P trend  = .011), and those who were not receiving prescription medication (P trend  = .036). Patient age, sex, race/ethnicity, income, education, and health conditions were associated with BDS use. The overall use of BDS remained stable during 1999 through 2014 for US adults with and without cancer, but it varied by individual characteristics. Cancer 2018;124:1207-15. © 2017 American Cancer Society. © 2017 American Cancer

Associations between Young Adult Romantic Relationship Quality and Problem Behaviors: An Examination of Personality-Environment Interactions

NARCIS (Netherlands)

Yu, Rongqin; Branje, Susan; Keijsers, Loes; Meeus, Wim

2015-01-01

This longitudinal study examined person-environment interplay by testing interaction effects between adolescent personality type (i.e., overcontrollers, undercontrollers, and resilients) and young adult romantic relationship quality on young adult delinquency and anxiety. The study employed six

Associations between young adult romantic relationship quality and problem behaviors : An examination of personality-environment interactions

NARCIS (Netherlands)

Yu, Rongqin; Branje, Susan; Keijsers, Loes; Meeus, W.H.J.

This longitudinal study examined person–environment interplay by testing interaction effects between adolescent personality type (i.e., overcontrollers, undercontrollers, and resilients) and young adult romantic relationship quality on young adult delinquency and anxiety. The study employed six

Parental Anxiety and Child Symptomatology: An Examination of Additive and Interactive Effects of Parent Psychopathology

Science.gov (United States)

Burstein, Marcy; Ginsburg, Golda S.; Tein, Jenn-Yun

2010-01-01

The current study examined relations between parent anxiety and child anxiety, depression, and externalizing symptoms. In addition, the study tested the additive and interactive effects of parent anxiety with parent depression and externalizing symptoms in relation to child symptoms. Forty-eight parents with anxiety disorders and 49 parents…

Viruses, bacteria, and parasites - oh my! a resurgence of interest in microbial-based therapy for cancer.

Science.gov (United States)

Zloza, Andrew

2018-01-08

As infections and cancer are two of the most common maladies affecting human beings, a concerted effort is needed to better understand their potential interactions and to further explore their use in microbial-based cancer treatments. Studies focusing on the interaction between pathogens and cancer began over 4000 years ago, but therapeutic application of pathogens has often been bypassed as other cancer therapies have gained wider interest. To many, the field of microbial-based cancer treatment may feel antiquated and already sufficiently explored. However, closer examination reveals that our current knowledge is but a series of dim reflections amongst many yet-unexplored shadows. Particularly, with our increased understanding of pathogen entry, replication, and senescence, coupled with our quickly increasing knowledge regarding cancer initiation, growth, and metastasis, and capped by our realization of the complexity and plasticity of the immune response, we are just now beginning to realize the vastness of the undiscovered area encompassing this field. At the same time, we are now uniquely poised with gained knowledge and discovered tools to join together across disciplines, uncover new positive and negative interactions between pathogens and cancer, and make important progress toward saving cancer patient lives.

Skin Cancer Surveillance Behaviors among Childhood Cancer Survivors

OpenAIRE

Stapleton, Jerod L.; Tatum, Kristina L.; Devine, Katie A.; Stephens, Sue; Masterson, Margaret; Baig, Amna; Hudson, Shawna V.; Coups, Elliot J.

2015-01-01

The risk of developing skin cancer is elevated among childhood cancer survivors (CCS), particularly among those treated with radiation. This survey study examined the skin cancer surveillance behaviors of 94 CCS. Approximately 48% of CCS had ever conducted skin self-examination and 31% had ever received a physician skin examination. Rates of physician skin examination were 2.5 times higher among CCS treated with radiation compared to those without radiation. However, rates of skin self-examin...

An oncogenic mutant of RHEB, RHEB Y35N, exhibits an altered interaction with BRAF resulting in cancer transformation.

Science.gov (United States)

Heard, Jeffrey J; Phung, Ivy; Potes, Mark I; Tamanoi, Fuyuhiko

2018-01-10

RHEB is a unique member of the RAS superfamily of small GTPases expressed in all tissues and conserved from yeast to humans. Early studies on RHEB indicated a possible RHEB-RAF interaction, but this has not been fully explored. Recent work on cancer genome databases has revealed a reoccurring mutation in RHEB at the Tyr35 position, and a recent study points to the oncogenic potential of this mutant that involves activation of RAF/MEK/ERK signaling. These developments prompted us to reassess the significance of RHEB effect on RAF, and to compare mutant and wild type RHEB. To study RHEB-RAF interaction, and the effect of the Y35N mutation on this interaction, we used transfection, immunoprecipitation, and Western blotting techniques. We generated cell lines stably expressing RHEB WT, RHEB Y35N, and KRAS G12V, and monitored cellular transforming properties through cell proliferation, anchorage independent growth, cell cycle analysis, and foci formation assays. We observe a strong interaction between RHEB and BRAF, but not with CRAF. This interaction is dependent on an intact RHEB effector domain and RHEB-GTP loading status. RHEB overexpression decreases RAF activation of the RAF/MEK/ERK pathway and RHEB knockdown results in an increase in RAF/MEK/ERK activation. RHEB Y35N mutation has decreased interaction with BRAF, and RHEB Y35N cells exhibit greater BRAF/CRAF heterodimerization resulting in increased RAF/MEK/ERK signaling. This leads to cancer transformation of RHEB Y35N stably expressing cell lines, similar to KRAS G12 V expressing cell lines. RHEB interaction with BRAF is crucial for inhibiting RAF/MEK/ERK signaling. The RHEB Y35N mutant sustains RAF/MEK/ERK signaling due to a decreased interaction with BRAF, leading to increased BRAF/CRAF heterodimerization. RHEB Y35N expressing cells undergo cancer transformation due to decreased interaction between RHEB and BRAF resulting in overactive RAF/MEK/ERK signaling. Taken together with the previously established

Gynecologic examination and cervical biopsies after (chemo) radiation for cervical cancer to identify patients eligible for salvage surgery

NARCIS (Netherlands)

Nijhuis, Esther R.; van der Zee, Ate G. J.; In 't Hout, Bertha A.; Boomgaard, Jantine J.; de Hullu, Joanne A.; Pras, Elisabeth; Hollema, Harry; Aalders, Jan G.; Jijman, Hans W.; Willemse, Pax H. B.; Mourits, Marian J. E.

2006-01-01

Purpose: The aim of this study was to evaluate efficacy of gynecologic examination under general anesthesia with cervical biopsies after (chemo) radiation for cervical cancer to identify patients with residual disease who may benefit from salvage surgery. Methods and Materials: In a retrospective

Gynecologic examination and cervical biopsies after (chemo) radiation for cervical cancer to identify patients eligible for salvage surgery.

NARCIS (Netherlands)

Nijhuis, E.R.; Zee, A.G. van der; Hout, B.A. van; Boomgaard, J.J.; Hullu, J.A. de; Pras, E.; Hollema, H.; Aalders, J.G.; Nijman, H.W.; Willemse, P.H.B.; Mourits, M.J.E.

2006-01-01

PURPOSE: The aim of this study was to evaluate efficacy of gynecologic examination under general anesthesia with cervical biopsies after (chemo) radiation for cervical cancer to identify patients with residual disease who may benefit from salvage surgery. METHODS AND MATERIALS: In a retrospective

Double Jeopardy? Age, Race, and HRQOL in Older Adults with Cancer

International Nuclear Information System (INIS)

Bellizzi, K. M.; Aziz, N. M.; Rowland, J. H.; Arora, N. K.

2012-01-01

Understanding the post-treatment physical and mental function of older adults from ethnic/racial minority backgrounds with cancer is a critical step to determine the services required to serve this growing population. The double jeopardy hypothesis suggests being a minority and old could have compounding effects on health. This population-based study examined the physical and mental function of older adults by age (mean age=75.7, SD=6.1), ethnicity/race, and cancer (breast, prostate, colorectal, and gynecologic) as well as interaction effects between age, ethnicity/race and HRQOL. There was evidence of a significant age by ethnicity/race interaction in physical function for breast, prostate and all sites combined, but the interaction became non-significant (for breast and all sites combined) when co morbidity was entered into the model. The interaction persisted in the prostate cancer group after controlling for co morbidity, such that African Americans and Asian Americans in the 75-79 age group report lower physical health than non-Hispanic Whites and Hispanic Whites in this age group. The presence of double jeopardy in the breast and all sites combined group can be explained by a differential co morbid burden among the older (75-79) minority group, but the interaction found in prostate cancer survivors does not reflect this differential co morbid burden.

Double Jeopardy? Age, Race, and HRQOL in Older Adults with Cancer

Directory of Open Access Journals (Sweden)

Keith M. Bellizzi

2012-01-01

Full Text Available Understanding the post-treatment physical and mental function of older adults from ethnic/racial minority backgrounds with cancer is a critical step to determine the services required to serve this growing population. The double jeopardy hypothesis suggests being a minority and old could have compounding effects on health. This population-based study examined the physical and mental function of older adults by age (mean age = 75.7, SD = 6.1, ethnicity/race, and cancer (breast, prostate, colorectal, and gynecologic as well as interaction effects between age, ethnicity/race and HRQOL. There was evidence of a significant age by ethnicity/race interaction in physical function for breast, prostate and all sites combined, but the interaction became non-significant (for breast and all sites combined when comorbidity was entered into the model. The interaction persisted in the prostate cancer group after controlling for comorbidity, such that African Americans and Asian Americans in the 75–79 age group report lower physical health than non-Hispanic Whites and Hispanic Whites in this age group. The presence of double jeopardy in the breast and all sites combined group can be explained by a differential comorbid burden among the older (75–79 minority group, but the interaction found in prostate cancer survivors does not reflect this differential comorbid burden.

Changes in Cytokines of the Bone Microenvironment during Breast Cancer Metastasis

International Nuclear Information System (INIS)

Sosnoski, D.M.; Krishnan, V.; Mastro, A.M.; Kraemer, W.J.; Dunn-Lewis, C.

2012-01-01

It is commonly accepted that cancer cells interact with host cells to create a microenvironment favoring malignant colonization. The complex bone microenvironment produces an ever changing array of cytokines and growth factors. In this study, we examined levels of MCP-1, IL-6, KC, MIP-2, VEGF, MIG, and eotaxin in femurs of athymic nude mice inoculated via intracardiac injection with MDA-MB-231GFP human metastatic breast cancer cells, MDA-MB-231 BRMS1GFP, a metastasis suppressed variant, or PBS. Animals were euthanized (day 3, 11, 19, 27 after injection) to examine femoral cytokine levels at various stages of cancer cell colonization. The epiphysis contained significantly more cytokines than the diaphysis except for MIG which was similar throughout the bone. Variation among femurs was evident within all groups. By day 27, MCP-1, MIG, VEGF and eotaxin levels were significantly greater in femurs of cancer cell-inoculated mice. These pro-osteoclastic and angiogenic cytokines may manipulate the bone microenvironment to enhance cancer cell colonization

Examining the Influence of Cost Concern and Awareness of Low-cost Health Care on Cancer Screening among the Medically Underserved.

Science.gov (United States)

Best, Alicia L; Strane, Alcha; Christie, Omari; Bynum, Shalanda; Wiltshire, Jaqueline

2017-01-01

African Americans suffer a greater burden of mortality from breast, cervical, and colorectal cancers than other groups in the United States. Early detection through timely screening can improve survival outcomes; however, cost is frequently reported as a barrier to screening. Federally qualified health centers (FQHCs) provide preventive and primary care to underserved populations regardless of ability to pay, positioning them to improve cancer screening rates. The purpose of this study was to examine the influence of concern about health care cost (cost concern) and awareness of low-cost health care (awareness) on cancer screening among 236 African Americans within an FQHC service area using self-report surveys. Multiple logistic regression indicated that awareness was positively associated with cervical and colorectal cancer screening, while cost concern was negatively associated with mammography screening. Results indicate that improving awareness and understanding of low-cost health care could increase cancer screening among underserved African Americans.

Interaction of Dietary Fatty Acids with Tumour Necrosis Factor Family Cytokines during Colon Inflammation and Cancer

Science.gov (United States)

Straková, Nicol; Vaculová, Alena Hyršlová; Tylichová, Zuzana; Šafaříková, Barbora; Kozubík, Alois

2014-01-01

Intestinal homeostasis is precisely regulated by a number of endogenous regulatory molecules but significantly influenced by dietary compounds. Malfunction of this system may result in chronic inflammation and cancer. Dietary essential n-3 polyunsaturated fatty acids (PUFAs) and short-chain fatty acid butyrate produced from fibre display anti-inflammatory and anticancer activities. Both compounds were shown to modulate the production and activities of TNF family cytokines. Cytokines from the TNF family (TNF-α, TRAIL, and FasL) have potent inflammatory activities and can also regulate apoptosis, which plays an important role in cancer development. The results of our own research showed enhancement of apoptosis in colon cancer cells by a combination of either docosahexaenoic acid (DHA) or butyrate with TNF family cytokines, especially by promotion of the mitochondrial apoptotic pathway and modulation of NFκB activity. This review is focused mainly on the interaction of dietary PUFAs and butyrate with these cytokines during colon inflammation and cancer development. We summarised recent knowledge about the cellular and molecular mechanisms involved in such effects and outcomes for intestinal cell behaviour and pathologies. Finally, the possible application for the prevention and therapy of colon inflammation and cancer is also outlined. PMID:24876678

Mouth self-examination as a screening tool for oral cancer in a high-risk group of patients with Fanconi anemia.

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Furquim, Camila Pinheiro; Pivovar, Allana; Cavalcanti, Laura Grein; Araújo, Renata Fuentes; Sales Bonfim, Carmem Maria; Torres-Pereira, Cassius Carvalho

2014-10-01

Oral cancer usually occurs at accessible sites, enabling early detection by visual inspection. Fanconi anemia (FA) is a recessive disorder associated with a high risk of developing head and neck solid tumors. The aim of this study was to assess the ability to perform mouth self-examination (MSE) in these patients. A total of 44 patients with FA, aged ≥ 18 years, were given a self-reported questionnaire to collect sociodemographic data and information about health-related behaviors and oral cancer awareness. They were asked to perform MSE, which was evaluated using criteria for mucosal visualization and retracting ability. Subsequently, an oral medicine specialist clinically examined all participants, and these findings were considered to be the gold standard. The sensitivity and specificity values of MSE were 43% and 44%, respectively. The MSE accuracy was 43%. Most patients (73%) reported that MSE was easy or very easy, although 75% showed insufficient performance. The accuracy of MSE alone is not sufficient to indicate whether MSE should be recommended as a strategy to prevent oral cancer in patients with FA. Nevertheless, the present results indicate that this inexpensive technique could be used as a tool for early detection of cancer in these patients. Copyright © 2014 Elsevier Inc. All rights reserved.

Predicting Variation of DNA Shape Preferences in Protein-DNA Interaction in Cancer Cells with a New Biophysical Model.

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Batmanov, Kirill; Wang, Junbai

2017-09-18

DNA shape readout is an important mechanism of transcription factor target site recognition, in addition to the sequence readout. Several machine learning-based models of transcription factor-DNA interactions, considering DNA shape features, have been developed in recent years. Here, we present a new biophysical model of protein-DNA interactions by integrating the DNA shape properties. It is based on the neighbor dinucleotide dependency model BayesPI2, where new parameters are restricted to a subspace spanned by the dinucleotide form of DNA shape features. This allows a biophysical interpretation of the new parameters as a position-dependent preference towards specific DNA shape features. Using the new model, we explore the variation of DNA shape preferences in several transcription factors across various cancer cell lines and cellular conditions. The results reveal that there are DNA shape variations at FOXA1 (Forkhead Box Protein A1) binding sites in steroid-treated MCF7 cells. The new biophysical model is useful for elucidating the finer details of transcription factor-DNA interaction, as well as for predicting cancer mutation effects in the future.

Knowledge of cervical cancer, attitude and husband’s support of Pap smear among multiparous women which have Pap’s smear examination in Aviati clinic Padang Bulan Medan

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Feriyawati, L.; Anggraini, D. R.; Fitrie, A. A.; Anggreini, R. N.

2018-03-01

Cervical cancer is a serious health problem and stated as the second cause of death of woman worldwide. Several studies have noted a higher incidence of cervical cancer with increasing parity. Early detection with Pap smear is proven to reduce mortality of patients. Knowledge, attitude and husband’s support contributed to theled womanto follow Pap smear examination. This study explores the knowledge of cervical cancer, attitude and husband’ s support of Pap smearin multiparous women that have Pap smear examination. This research is a quantitative study with cross sectional approach recruited 50 respondents as multiparous women that have Pap smear examination inAviati Clinic, Padang Bulan, Medan. The data were collected by self-reports using structured objectives by questionnaires. The result of this study showed that 66% respondents have high knowledge of cervical cancer and 76% respondents have ahigh attitude of Pap smear, but they almost have low husband’s support of Pap smear including information support (62%), emotional support (46%) and real support (50%). This study has revealed that multiparous women that had Pap smear examination generally had high knowledge about cervical cancer and positive attitude about Pap smear, even most of them had low husband’s support.

Lung Cancer and Human Papilloma Viruses (HPVs: Examining the Molecular Evidence

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Priya R. Prabhu

2012-01-01

Full Text Available Human papilloma virus (HPV, known to be an etiological agent for genital cancers, has been suggested also to be a possible contributory agent for lung cancer. Alternatively, lung cancer, formerly considered to be solely a smoker's disease, may now be more appropriately categorised into never smoker's and smoker's lung cancer. Through this paper we attempt to bring forth the current knowledge regarding mechanisms of HPV gaining access into the lung tissue, various strategies involved in HPV-associated tumorigenesis in lung tissue.

The Long Non-Coding RNA XIST Interacted with MiR-124 to Modulate Bladder Cancer Growth, Invasion and Migration by Targeting Androgen Receptor (AR).

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Xiong, Yaoyao; Wang, Long; Li, Yuan; Chen, Minfeng; He, Wei; Qi, Lin

2017-01-01

Long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) is involved in the progression of several tumors. The interaction between lncRNA and miRNA or miRNA's target genes is reported to play crucial roles in malignancy. In addition, Androgen receptor (AR) is considered to be involved in bladder cancer progression. In this study, we investigated the role of XIST in human bladder cancer and its interaction with miR-124 and AR. XIST and AR expression was detected in bladder tumor samples and cell lines. Effects of XIST and AR on bladder cancer cells growth, invasion and migration were analyzed. Bioinformatic analysis and luciferase assays were used to identify the interaction among XIST, AR and miR-124. The correlations of miR-124 with XIST and AR in bladder cancer samples were statistically analyzed. XIST and AR were upregulated in bladder cancer tissues and positively correlated. Higher XIST and AR expression were related to poorer TNM stage of bladder cancer. XIST knockdown reduced bladder cancer cells' proliferation, invasion and migration. While this inhibitory effect could be partially restored by AR overexpression. XIST inhibited miR-124 expression by directly targeting. Moreover, miR-124 could bind to the 3'UTR of AR to regulate its expression. MiR-124 inhibition partially restored the XIST knockdown-induced reduction of AR, c-myc, p27, MMP13 and MMP9 expression. In bladder cancer tissues, miR-124 level was inversely correlated with the expression of XIST and AR, respectively. These findings indicated that XIST might be an oncogenic lncRNA that promoted the bladder cancer growth, invasion and migration via miR-124 dependent AR regulation. © 2017 The Author(s). Published by S. Karger AG, Basel.

The Long Non-Coding RNA XIST Interacted with MiR-124 to Modulate Bladder Cancer Growth, Invasion and Migration by Targeting Androgen Receptor (AR

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Yaoyao Xiong

2017-08-01

Full Text Available Backgrounds/Aims: Long non-coding RNA (lncRNA X-inactive specific transcript (XIST is involved in the progression of several tumors. The interaction between lncRNA and miRNA or miRNA’s target genes is reported to play crucial roles in malignancy. In addition, Androgen receptor (AR is considered to be involved in bladder cancer progression. In this study, we investigated the role of XIST in human bladder cancer and its interaction with miR-124 and AR. Methods: XIST and AR expression was detected in bladder tumor samples and cell lines. Effects of XIST and AR on bladder cancer cells growth, invasion and migration were analyzed. Bioinformatic analysis and luciferase assays were used to identify the interaction among XIST, AR and miR-124. The correlations of miR-124 with XIST and AR in bladder cancer samples were statistically analyzed. Results: XIST and AR were upregulated in bladder cancer tissues and positively correlated. Higher XIST and AR expression were related to poorer TNM stage of bladder cancer. XIST knockdown reduced bladder cancer cells’ proliferation, invasion and migration. While this inhibitory effect could be partially restored by AR overexpression. XIST inhibited miR-124 expression by directly targeting. Moreover, miR-124 could bind to the 3’UTR of AR to regulate its expression. MiR-124 inhibition partially restored the XIST knockdown-induced reduction of AR, c-myc, p27, MMP13 and MMP9 expression. In bladder cancer tissues, miR-124 level was inversely correlated with the expression of XIST and AR, respectively. Conclusion: These findings indicated that XIST might be an oncogenic lncRNA that promoted the bladder cancer growth, invasion and migration via miR-124 dependent AR regulation.

Wild-type EGFR Is Stabilized by Direct Interaction with HSP90 in Cancer Cells and Tumors

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Aarif Ahsan

2012-08-01

Full Text Available The epidermal growth factor receptor (EGFR has been targeted for inhibition using tyrosine kinase inhibitors and monoclonal antibodies, with improvement in outcome in subsets of patients with head and neck, lung, and colorectal carcinomas. We have previously found that EGFR stability plays a key role in cell survival after chemotherapy and radiotherapy. Heat shock protein 90 (HSP90 is known to stabilize mutant EGFR and ErbB2, but its role in cancers with wild-type (WT WT-EGFR is unclear. In this report, we demonstrate that fully mature, membrane-bound WT-EGFR interacts with HSP90 independent of ErbB2. Further, the HSP90 inhibitors geldanamycin (GA and AT13387 cause a decrease in WT-EGFR in cultured head and neck cancer cells. This decrease results from a significantly reduced half-life of WT-EGFR. WT-EGFR was also lost in head and neck xenograft specimens after treatment with AT13387 under conditions that inhibited tumor growth and prolonged survival of the mice. Our findings demonstrate that WT-EGFR is a client protein of HSP90 and that their interaction is critical for maintaining both the stability of the receptor as well as the growth of EGFR-dependent cancers. Furthermore, these findings support the search for specific agents that disrupt HSP90's ability to act as an EGFR chaperone.

SDF-1alpha concentration dependent modulation of RhoA and Rac1 modifies breast cancer and stromal cells interaction

International Nuclear Information System (INIS)

Pasquier, Jennifer; Abu-Kaoud, Nadine; Abdesselem, Houari; Madani, Aisha; Hoarau-Véchot, Jessica; Thawadi, Hamda Al.; Vidal, Fabien; Couderc, Bettina; Favre, Gilles; Rafii, Arash

2015-01-01

The interaction of SDF-1alpha with its receptor CXCR4 plays a role in the occurrence of distant metastasis in many solid tumors. This interaction increases migration from primary sites as well as homing at distant sites. Here we investigated how SDF-1α could modulate both migration and adhesion of cancer cells through the modulation of RhoGTPases. We show that different concentrations of SDF-1α modulate the balance of adhesion and migration in cancer cells. Increased migration was obtained at 50 and 100 ng/ml of SDF-1α; however migration was reduced at 200 ng/ml. The adhesion between breast cancer cells and BMHC was significantly increased by SDF-1α treatment at 200 ng/ml and reduced using a blocking monoclonal antibody against CXCR4. We showed that at low SDF-1α concentration, RhoA was activated and overexpressed, while at high concentration Rac1 was promoting SDF-1α mediating-cell adhesion. We conclude that SDF-1α concentration modulates migration and adhesion of breast cancer cells, by controlling expression and activation of RhoGTPases. The online version of this article (doi:10.1186/s12885-015-1556-7) contains supplementary material, which is available to authorized users

Multiparametric evaluation by simultaneous PET-MRI examination in patients with histologically proven laryngeal cancer

International Nuclear Information System (INIS)

Cavaliere, Carlo; Romeo, Valeria; Aiello, Marco; Mesolella, Massimo; Iorio, Brigida; Barbuto, Luigi; Cantone, Elena; Nicolai, Emanuele; Covello, Mario

2017-01-01

Highlights: • PET/MRI is feasible and useful for primary staging of laryngeal cancer. • PET/MRI simultaneously provides morphological, metabolic and functional parameters of tumoral laryngeal lesions. • PET/MRI allows an appropriate tumoral staging in terms of lesion extension with significant impact on therapeutic strategies. - Abstract: Objectives: To evaluate the relationship between metabolic 18Fluoro-Deoxyglucose-Positron Emission Tomography (18FDG/PET) and morpho-functional parameters derived by Magnetic Resonance Imaging (MRI) in patients with histologically proven laryngeal cancer. To assess the clinical impact of PET/MRI examination on patient’s staging and treatment planning. Methods: 16 patients with histologically proven laryngeal cancer were enrolled and underwent whole body PET/CT followed by a dedicated PET/MRI of the head/neck region. Data were separately evaluated by two blinded groups: metabolic (SUV and MTV), diffusion (ADC) and perfusion (K trans , V e , k ep and iAUC) maps were obtained by positioning regions of interest (ROIs). Tumoral local extension assessed on PET/MRI was compared to endoscopic findings. Results: A good inter-observer agreement was found in anatomical location and local extension of PET/MRI lesions (Cohen’s kappa 0.9). PET/CT SUV measures highly correlate with ones derived by PET/MRI (e.g., p = 0.96 for measures on VOI). Significant correlations among metabolic, diffusion and perfusion parameters have been detected. PET/MRI had a relevant clinical impact, confirming endoscopic findings (6 cases), helping treatment planning (9 cases), and modifying endoscopic primary staging (1 case). Conclusions: PET/MRI is useful for primary staging of laryngeal cancer, allowing simultaneous collection of metabolic and functional data and conditioning the therapeutic strategies.

Multiparametric evaluation by simultaneous PET-MRI examination in patients with histologically proven laryngeal cancer

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Cavaliere, Carlo [IRCCS SDN, Via E. Gianturco, 113-80143, Naples (Italy); Romeo, Valeria, E-mail: valeria.romeo@unina.it [Department of Advanced Biomedical Sciences, Federico II University, Naples (Italy); Aiello, Marco [IRCCS SDN, Via E. Gianturco, 113-80143, Naples (Italy); Mesolella, Massimo; Iorio, Brigida [Department of Neuroscience, Reproductive and Odontostomatologic Science, ENT Section, Federico II University, Naples (Italy); Barbuto, Luigi [Department of Advanced Biomedical Sciences, Federico II University, Naples (Italy); Cantone, Elena [Department of Neuroscience, Reproductive and Odontostomatologic Science, ENT Section, Federico II University, Naples (Italy); Nicolai, Emanuele; Covello, Mario [IRCCS SDN, Via E. Gianturco, 113-80143, Naples (Italy)

2017-03-15

Highlights: • PET/MRI is feasible and useful for primary staging of laryngeal cancer. • PET/MRI simultaneously provides morphological, metabolic and functional parameters of tumoral laryngeal lesions. • PET/MRI allows an appropriate tumoral staging in terms of lesion extension with significant impact on therapeutic strategies. - Abstract: Objectives: To evaluate the relationship between metabolic 18Fluoro-Deoxyglucose-Positron Emission Tomography (18FDG/PET) and morpho-functional parameters derived by Magnetic Resonance Imaging (MRI) in patients with histologically proven laryngeal cancer. To assess the clinical impact of PET/MRI examination on patient’s staging and treatment planning. Methods: 16 patients with histologically proven laryngeal cancer were enrolled and underwent whole body PET/CT followed by a dedicated PET/MRI of the head/neck region. Data were separately evaluated by two blinded groups: metabolic (SUV and MTV), diffusion (ADC) and perfusion (K{sub trans}, V{sub e}, k{sub ep} and iAUC) maps were obtained by positioning regions of interest (ROIs). Tumoral local extension assessed on PET/MRI was compared to endoscopic findings. Results: A good inter-observer agreement was found in anatomical location and local extension of PET/MRI lesions (Cohen’s kappa 0.9). PET/CT SUV measures highly correlate with ones derived by PET/MRI (e.g., p = 0.96 for measures on VOI). Significant correlations among metabolic, diffusion and perfusion parameters have been detected. PET/MRI had a relevant clinical impact, confirming endoscopic findings (6 cases), helping treatment planning (9 cases), and modifying endoscopic primary staging (1 case). Conclusions: PET/MRI is useful for primary staging of laryngeal cancer, allowing simultaneous collection of metabolic and functional data and conditioning the therapeutic strategies.

Multiparametric evaluation by simultaneous PET-MRI examination in patients with histologically proven laryngeal cancer.

Science.gov (United States)

Cavaliere, Carlo; Romeo, Valeria; Aiello, Marco; Mesolella, Massimo; Iorio, Brigida; Barbuto, Luigi; Cantone, Elena; Nicolai, Emanuele; Covello, Mario

2017-03-01

To evaluate the relationship between metabolic 18Fluoro-Deoxyglucose-Positron Emission Tomography (18FDG/PET) and morpho-functional parameters derived by Magnetic Resonance Imaging (MRI) in patients with histologically proven laryngeal cancer. To assess the clinical impact of PET/MRI examination on patient's staging and treatment planning. 16 patients with histologically proven laryngeal cancer were enrolled and underwent whole body PET/CT followed by a dedicated PET/MRI of the head/neck region. Data were separately evaluated by two blinded groups: metabolic (SUV and MTV), diffusion (ADC) and perfusion (K trans , V e , k ep and iAUC) maps were obtained by positioning regions of interest (ROIs). Tumoral local extension assessed on PET/MRI was compared to endoscopic findings. A good inter-observer agreement was found in anatomical location and local extension of PET/MRI lesions (Cohen's kappa 0.9). PET/CT SUV measures highly correlate with ones derived by PET/MRI (e.g., p=0.96 for measures on VOI). Significant correlations among metabolic, diffusion and perfusion parameters have been detected. PET/MRI had a relevant clinical impact, confirming endoscopic findings (6 cases), helping treatment planning (9 cases), and modifying endoscopic primary staging (1 case). PET/MRI is useful for primary staging of laryngeal cancer, allowing simultaneous collection of metabolic and functional data and conditioning the therapeutic strategies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effects of an Educational Intervention on Breast Self-Examination, Breast Cancer Prevention-Related Knowledge, and Healthy Lifestyles in Scholars from a Low-Income Area in Bogota, Colombia.

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Masso-Calderón, A M; Meneses-Echávez, J F; Correa-Bautista, J E; Tovar-Cifuentes, A; Alba-Ramírez, P A; Charry-Ángel, C E

2016-11-04

The aim of this study was to evaluate the effects of an educational intervention on breast self-examination, cancer prevention-related knowledge, practices, and behavior change in scholars from a low-income area in Bogota, Colombia. Uncontrolled trial was conducted in 155 scholars. Two educational sessions, 90 min each, were carried out in March 2015 according to the Colombian guidelines for educational communication in the framework of cancer control. All participants completed a self-reported questionnaire at pre- and post-intervention, as well as 1, 3, and 6 months after the intervention. Breast self-examination was practiced by 78.1% of the scholars, and the overall knowledge of breast cancer risk factors was poor. The educational intervention resulted in significant improvements on breast self-examination practice, the knowledge of the technique, and the knowledge of the main risk factors for breast cancer as well as the practice of physical activity and vegetable intake at 6 months follow-up. An educational intervention according to the Colombian guidelines for educational communication in the framework of cancer control improved the practice of breast self-examination, cancer prevention-related knowledge, as well as the practice of physical activity and vegetable consumption in scholars from a low-income area in Bogota, Colombia. Further randomized controlled studies are warranted.

The value of the repeated examination of BRAF V600E mutation status in diagnostics of papillary thyroid cancer.

Science.gov (United States)

Beiša, Augustas; Beiša, Virgilijus; Stoškus, Mindaugas; Ostanevičiūtė, Elvyra; Griškevičius, Laimonas; Strupas, Kęstutis

2016-01-01

Nodular thyroid disease is one of the most frequently diagnosed pathologies of the adult population in iodine-deficient regions. Approximately 30% of thyroid aspirates are classified as nondiagnostic/unsatisfactory or indeterminate. However, patients with indeterminate cytology still undergo surgery. The object of this study was to determine the diagnostic value of re-examining the BRAF V600E mutation in papillary thyroid carcinoma patients. All patients underwent ultrasound guided fine-needle aspiration of a thyroid nodule. They were assigned to one of the four groups (indeterminate or positive for malignant cells) of the Bethesda System for Reporting Thyroid Cytopathology. Genetic investigation of the BRAF V600E mutation was performed for all of the fine-needle aspiration cytology specimens. All of the patients underwent surgery. Subsequently, histological investigation of the removed tissues was performed. Additional analysis of the BRAF V600E mutation from the histology specimen was then performed for the initially BRAF-negative cases. Two hundred and fourteen patients were involved in the study. One hundred and six (49.53%) patients were diagnosed with thyroid cancer. Of these 106 patients, 95 (89.62%) patients were diagnosed with papillary thyroid cancer. The BRAF V600E mutation was positive in 62 (65.26%) and negative in 33 (34.74%) histologically confirmed papillary thyroid cancer cases. After the genetic investigation, a total of 74 (77.89%) papillary thyroid cancer cases were positive for the BRAF V600E mutation and 21 (22.11%) were negative. Repeated examination of the BRAF V600E mutation status in the fine-needle aspiration may potentially increase the sensitivity of papillary thyroid cancer diagnostics.

Folate intake, alcohol consumption, and the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism: influence on prostate cancer risk and interactions

International Nuclear Information System (INIS)

Kobayashi, Lindsay C.; Limburg, Heather; Miao, Qun; Woolcott, Christy; Bedard, Leanne L.; Massey, Thomas E.; Aronson, Kristan J.

2012-01-01

Purpose: Folate is essential to DNA methylation and synthesis and may have a complex dualistic role in prostate cancer. Alcohol use may increase risk and epigenetic factors may interact with lifestyle exposures. We aimed to characterize the independent and joint effects of folate intake, alcohol consumption, and the MTHFR C677T gene polymorphism on prostate cancer risk, while accounting for intakes of vitamins B 2 , B 6 , B 12 , methionine, total energy, and confounders. Methods: A case-control study was conducted at Kingston General Hospital of 80 incident primary prostate cancer cases and 334 urology clinic controls, all with normal age-specific PSA levels (to exclude latent prostate cancers). Participants completed a questionnaire on folate and alcohol intakes and potential confounders prior to knowledge of diagnosis, eliminating recall bias, and blood was drawn for MTHFR genotyping. Joint effects of exposures were assessed using unconditional logistic regression and significance of multiplicative and additive interactions using general linear models. Results: Folate, vitamins B 2 , B 6 , B 12 , methionine, and the CT and TT genotypes were not associated with prostate cancer risk. The highest tertile of lifetime alcohol consumption was associated with increased risk (OR = 2.08; 95% CI: 1.12–3.86). Consumption of >5 alcoholic drinks per week was associated with increased prostate cancer risk among men with low folate intake (OR = 2.38; 95% CI: 1.01–5.57), and higher risk among those with the CC MTHFR genotype (OR = 4.43; 95% CI: 1.15–17.05). Increased risk was also apparent for average weekly alcohol consumption when accounting for the multiplicative interaction between folate intake and MTHFR C677T genotype (OR = 3.22; 95% CI: 1.36–7.59). Conclusion: Alcohol consumption is associated with increased prostate cancer risk, and this association is stronger among men with low folate intake, with the CC MTHFR genotype, and when accounting for the joint effect

Folate intake, alcohol consumption, and the methylenetetrahydrofolate reductase (MTHFR C677T gene polymorphism: influence on prostate cancer risk and interactions

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Lindsay C Kobayashi

2012-08-01

Full Text Available Purpose: Folate is essential to DNA methylation and synthesis and may have a complex dualistic role in prostate cancer. Alcohol use may increase risk and epigenetic factors may interact with lifestyle exposures. We aimed to characterize the independent and joint effects of folate intake, alcohol consumption, and the MTHFR C677T gene polymorphism on prostate cancer risk, while accounting for intakes of vitamins B2, B6, B12, methionine, total energy, and confounders.Methods: A case-control study was conducted at Kingston General Hospital of 80 incident primary prostate cancer cases and 334 urology clinic controls, all with normal age-specific PSA levels (to exclude latent prostate cancers. Participants completed a questionnaire on folate and alcohol intakes and potential confounders prior to knowledge of diagnosis, eliminating recall bias, and blood was drawn for MTHFR genotyping. Joint effects of exposures were assessed using unconditional logistic regression and significance of multiplicative and additive interactions using general linear models.Results: Folate, vitamins B2, B6, B12, methionine, and the CT and TT genotypes were not associated with prostate cancer risk. The highest tertile of lifetime alcohol consumption was associated with increased risk (OR=2.08; 95% CI: 1.12-3.86. Consumption of >5 alcoholic drinks/week was associated with increased prostate cancer risk among men with low folate intake (OR=2.38; 95% CI: 1.01-5.57 and higher risk among those with the CC MTHFR genotype (OR=4.43; 95% CI: 1.15-17.05. Increased risk was also apparent for weekly alcohol consumption when accounting for the multiplicative interaction between folate intake and MTHFR C677T genotype (OR=3.22; 95% CI: 1.36-7.59.Conclusion: Alcohol consumption is associated with increased prostate cancer risk, and this association is stronger among men with low folate intake, with the CC MTHFR genotype, and when accounting for the joint effect of folate intake and MTHFR C

Role of Cytokine-Induced Glycosylation Changes in Regulating Cell Interactions and Cell Signaling in Inflammatory Diseases and Cancer

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Justine H. Dewald

2016-11-01

Full Text Available Glycosylation is one of the most important modifications of proteins and lipids, and cell surface glycoconjugates are thought to play important roles in a variety of biological functions including cell-cell and cell-substrate interactions, bacterial adhesion, cell immunogenicity and cell signaling. Alterations of glycosylation are observed in number of diseases such as cancer and chronic inflammation. In that context, pro-inflammatory cytokines have been shown to modulate cell surface glycosylation by regulating the expression of glycosyltransferases involved in the biosynthesis of carbohydrate chains. These changes in cell surface glycosylation are also known to regulate cell signaling and could contribute to disease pathogenesis. This review summarizes our current knowledge of the glycosylation changes induced by pro-inflammatory cytokines, with a particular focus on cancer and cystic fibrosis, and their consequences on cell interactions and signaling.

A practical approach to radiological evaluation of CT lung cancer screening examinations

NARCIS (Netherlands)

Xie, Xueqian; Heuvelmans, Marjolein A.; van Ooijen, Peter M. A.; Oudkerk, Matthijs; Vliegenthart, Rozemarijn

2013-01-01

Lung cancer is the most common cause of cancer-related death in the world. The Dutch-Belgian Randomized Lung Cancer Screening Trial (Dutch acronym: NELSON) was launched to investigate whether screening for lung cancer by low-dose multidetector computed tomography (CT) in high-risk patients will lead

Skin Cancer Surveillance Behaviors Among Childhood Cancer Survivors.

Science.gov (United States)

Stapleton, Jerod L; Tatum, Kristina L; Devine, Katie A; Stephens, Sue; Masterson, Margaret; Baig, Amna; Hudson, Shawna V; Coups, Elliot J

2016-03-01

The risk of developing skin cancer is elevated among childhood cancer survivors (CCS), particularly among those treated with radiation. This survey study examined the skin cancer surveillance behaviors of 94 CCS. Approximately 48% of CCS had ever conducted skin self-examination (SSE) and 31% had ever received a physician skin examination. Rates of physician skin examination were 2.5 times higher among CCS treated with radiation compared to those without radiation. However, rates of SSEs did not differ based on treatment history. These findings highlight the need to promote skin cancer surveillance as an important aspect of CCS survivorship care. © 2015 Wiley Periodicals, Inc.

Interactions between epigenetics and metabolism in cancers

International Nuclear Information System (INIS)

Yun, Jihye; Johnson, Jared L.; Hanigan, Christin L.; Locasale, Jason W.

2012-01-01

Cancer progression is accompanied by widespread transcriptional changes and metabolic alterations. While it is widely accepted that the origin of cancer can be traced to the mutations that accumulate over time, relatively recent evidence favors a similarly fundamental role for alterations in the epigenome during tumorigenesis. Changes in epigenetics that arise from post-translational modifications of histones and DNA are exploited by cancer cells to upregulate and/or downregulate the expression levels of oncogenes and tumor suppressors, respectively. Although the mechanisms behind these modifications, in particular how they lead to gene silencing and activation, are still being understood, most of the enzymatic machinery of epigenetics require metabolites as substrates or cofactors. As a result, their activities can be influenced by the metabolic state of the cell. The purpose of this review is to give an overview of cancer epigenetics and metabolism and provide examples of where they converge.

Impact of diabetes on oncologic outcome of colorectal cancer patients: colon vs. rectal cancer.

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Justin Y Jeon

Full Text Available BACKGROUND: To evaluate the impact of diabetes on outcomes in colorectal cancer patients and to examine whether this association varies by the location of tumor (colon vs. rectum. PATIENTS AND METHODS: This study includes 4,131 stage I-III colorectal cancer patients, treated between 1995 and 2007 (12.5% diabetic, 53% colon, 47% rectal in South Korea. Cox proportional hazards modeling was used to determine the prognostic influence of DM on survival endpoints. RESULTS: Colorectal cancer patients with DM had significantly worse disease-free survival (DFS [hazard ratio (HR 1.17, 95% confidence interval (CI: 1.00-1.37] compared with patients without DM. When considering colon and rectal cancer independently, DM was significantly associated with worse overall survival (OS (HR: 1.46, 95% CI: 1.11-1.92, DFS (HR: 1.45, 95% CI: 1.15-1.84 and recurrence-free survival (RFS (HR: 1.32, 95% CI: 0.98-1.76 in colon cancer patients. No association for OS, DFS or RFS was observed in rectal cancer patients. There was significant interaction of location of tumor (colon vs. rectal cancer with DM on OS (P = 0.009 and DFS (P = 0.007. CONCLUSIONS: This study suggests that DM negatively impacts survival outcomes of patients with colon cancer but not rectal cancer.

Interactions between smoking and other exposures associated with lung cancer risk in women: diet and physical activity.

Science.gov (United States)

Kubík, A; Zatloukal, P; Tomásek, L; Pauk, N; Havel, L; Dolezal, J; Plesko, I

2007-01-01

The objective of the study is to estimate the differences in the impact of diet and physical exercise on lung cancer risk in female nonsmokers vs. smokers, and reveal interactions, if any. In a hospital based case-control study, data collected by in-person interviews from 569 female lung cancer cases and 2120 controls were analyzed using unconditional logistic regression stratifying by appropriate factors. Protective effects were observed for intake of milk/dairy products (OR=0.57, 95%CI 0.35-0.94), vegetables (OR=0.60, 95%CI 0.40-0.91), apples (OR=0.69), wine (OR=0.77), and physical exercise (OR=0.59, 95%CI 0.42-0.83) among smokers only, while no similar effects were found among nonsmokers. In contrast, the intake of black tea was associated with a protective effect (OR=0.66, 95%CI 0.47-0.94) among nonsmokers only. Comparing the effects of dietary items and physical activity on lung cancer risk among nonsmokers versus smokers, statistically significant effect modifications were found for black tea (P 0.005), and milk/dairy products (P 0.047). Borderline effect modifications emerged for physical exercise (P 0.077). These results indicate protective effects of some components of healthful diet and physical exercise among smokers, and of the intake of black tea among nonsmokers. The observed interactions of the impact of black tea, milk/dairy products and physical activity upon lung cancer risk in women at different levels of the smoking habit deserve further studies.

Knowledge Regarding Symptoms and Risk Factors and Screening of Breast Cancer in Women Under 30 Years and Their Practice Relative to Self-Examination

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F. Jafari

2013-08-01

Full Text Available Background: Breast cancer is the most common malignancy among women worldwide. In Iran, breast cancer ranks first among cancers diagnosed in women. Nevertheless, many of women haven’t enough knowledge about breast cancer risk factors and symptoms. The main reason for this escalating mortality is lack of awareness and late diagnosis of disease. The aim of present study assessed the knowledge about risk factors and symptoms of breast cancer, also the screening method and practice (Breast self examination about it. Methods: This is a descriptive and cross-sectional study. In this study 340 red crescent volunteer women participated in a national congress were selected with convenience sampling method. The data collection instrument consisted of a three part questionnaire which included demographic factors, Knowledge level about risk factors, symptoms and screening methods of breast cancer and questions concerning practice about breast self examination (BSE.The study tool was a researcher-designed questionnaire which could evaluated a number of variables. After data collection, analysis was carried out with descriptive tests by SPSS.16 software. Results: The mean age of subjects was 23±2.1yrs. Knowledge about breast cancer risk factors was very poor, the most widely known risk factor and lowest among the participants was family history of breast cancer (30.6 % and early menarche (under 12 years (0.3% respectively. Only 47.9% respondents correctly recognized breast lump and 11.2% breast discharge as the most common symptoms of breast cancer.30% of subjects were aware of BSE. However, a lesser proportion (9.4% was done BSE regular monthly every few months. Conclusion: Regarding the low level of the women’s knowledge about breast cancer especially in young educated women, screening and interventional programs to improve awareness and practice is essential.

Grb7 SH2 domain structure and interactions with a cyclic peptide inhibitor of cancer cell migration and proliferation

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Pero Stephanie C

2007-09-01

Full Text Available Abstract Background Human growth factor receptor bound protein 7 (Grb7 is an adapter protein that mediates the coupling of tyrosine kinases with their downstream signaling pathways. Grb7 is frequently overexpressed in invasive and metastatic human cancers and is implicated in cancer progression via its interaction with the ErbB2 receptor and focal adhesion kinase (FAK that play critical roles in cell proliferation and migration. It is thus a prime target for the development of novel anti-cancer therapies. Recently, an inhibitory peptide (G7-18NATE has been developed which binds specifically to the Grb7 SH2 domain and is able to attenuate cancer cell proliferation and migration in various cancer cell lines. Results As a first step towards understanding how Grb7 may be inhibited by G7-18NATE, we solved the crystal structure of the Grb7 SH2 domain to 2.1 Å resolution. We describe the details of the peptide binding site underlying target specificity, as well as the dimer interface of Grb 7 SH2. Dimer formation of Grb7 was determined to be in the μM range using analytical ultracentrifugation for both full-length Grb7 and the SH2 domain alone, suggesting the SH2 domain forms the basis of a physiological dimer. ITC measurements of the interaction of the G7-18NATE peptide with the Grb7 SH2 domain revealed that it binds with a binding affinity of Kd = ~35.7 μM and NMR spectroscopy titration experiments revealed that peptide binding causes perturbations to both the ligand binding surface of the Grb7 SH2 domain as well as to the dimer interface, suggesting that dimerisation of Grb7 is impacted on by peptide binding. Conclusion Together the data allow us to propose a model of the Grb7 SH2 domain/G7-18NATE interaction and to rationalize the basis for the observed binding specificity and affinity. We propose that the current study will assist with the development of second generation Grb7 SH2 domain inhibitors, potentially leading to novel inhibitors of

Significance of pelvic CT examination for the diagnosis of the distal colonic and rectal cancer

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Shindo, Takeshi

1984-01-01

Pelvic CT examination was performed in preoperative 40 patients and postoperrative 51 patients of the distal colonic and rectal carcinoma. CT study expect for the decision of the depth of invasion and the detection of lymphnode metastasis, or the location of recurrence. Diagnostic accuracy rate of the depth of invasion was 68.6% in tumors of sigmoid colon, rectosigmoid, and upper rectum, and 78.9% in lower rectum, and anal canal. These rate were superior to those of selective angiographic examination. Diagnostic accuracy rate for lymphnode metastasis was 73.0%. CT examination could define the lymphnode swelling, but could not define if those were metastasis or not. Furthermore, CT-angiography was beneficial for the estimation of the depth of invasion. The differentiation between local recurrent tumor and granulomatous mass in the perineum after abdomino-perineal resection is the most important problem, however, the further studies are necessary to obtain the definite criteria of differential diagnosis. Above results support that CT examination should be used routinely in the distal colonic and rectal cancer patients. (author)

AURKA Phe31Ile polymorphism interacted with use of alcohol, betel quid, and cigarettes at multiplicative risk of oral cancer occurrence.

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Lee, Chi-Pin; Chiang, Shang-Lun; Lee, Chien-Hung; Tsai, Yi-Shan; Wang, Zhi-Hong; Hua, Chun-Hung; Chen, Yuan-Chien; Tsai, Eing-Mei; Ko, Ying-Chin

2015-11-01

The expression levels of two DNA repair genes (CHAF1A and CHAF1B) and a chromosome segregation gene (AURKA) were susceptible to arecoline exposure, a major alkaloid of areca nut. We hypothesize that genetic variants of these genes might also be implicated in the risk of oral cancer and could be modified by substance use of betel quid or alcohol and cigarettes. A case-control study, which included 507 patients with oral cancer and 717 matched controls, was performed in order to evaluate the cancer susceptibility by the tagging single-nucleotide polymorphisms (tagSNPs) in AURKA, CHAF1A, and CHAF1B using a genotyping assay and gene-environment interaction analysis. The Phe31Ile polymorphism (rs2273535, T91A) of AURKA was significantly associated with an increased risk of oral cancer (odds ratio (OR) = 2.1, 95% confidence interval (CI) 1.2-3.5). The gene dosage of the 91A allele also showed a significant trend in risk of oral cancer (P = 0.008). Furthermore, we found the AURKA 91AA homozygote was modifiable by substance use of alcohol, betel quid, and cigarettes (ABC), leading to increased risk of oral cancer in an additive or a multiplicative model (combined effect indexes = 1.2-4.0 and 1.5-2.2, respectively). However, no association was observed between the genetic variants of CHAF1A or CHAF1B and oral cancer risk in the study. These findings reveal the functional Phe31Ile polymorphism tagSNP of AURKA may be a strong susceptibility gene in ABC-related oral cancer occurrence. The results of this betel-related oral cancer study provide the evidence of environment-gene interaction for early prediction and molecular diagnosis.

Interactions between epigenetics and metabolism in cancers

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Jihye eYun

2012-11-01

Full Text Available Cancer progression is accompanied by widespread transcriptional changes and metabolic alterations. Although it is widely accepted that the origin of cancer can be traced to the mutations that accumulate over time, relatively recent evidence favors a similarly fundamental role for alterations in the epigenome during tumorigenesis. Changes in epigenetics that arise from post-translational modifications of histones and DNA, are exploited by cancer cells to upregulate and/or downregulate the expression levels of oncogenes and tumor suppressors, respectively. Although the mechanisms behind these modifications, in particular how they lead to gene silencing and activation, are still being understood, many enzymes that carry out post-translational modifications that alter epigenetics require metabolites as substrates or cofactors. As a result, their activities can be influenced by the metabolic state of the cell. The purpose of this review is to give an overview of cancer epigenetics and metabolism and provide examples of where they converge.

Hypoxia enhances the interaction between pancreatic stellate cells and cancer cells via increased secretion of connective tissue growth factor.

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Eguchi, Daiki; Ikenaga, Naoki; Ohuchida, Kenoki; Kozono, Shingo; Cui, Lin; Fujiwara, Kenji; Fujino, Minoru; Ohtsuka, Takao; Mizumoto, Kazuhiro; Tanaka, Masao

2013-05-01

Pancreatic cancer (PC), a hypovascular tumor, thrives under hypoxic conditions. Pancreatic stellate cells (PSCs) promote PC progression by secreting soluble factors, but their functions in hypoxia are poorly understood. This study aimed to clarify the effects of hypoxic conditions on the interaction between PC cells and PSCs. We isolated human PSCs from fresh pancreatic ductal adenocarcinomas and analyzed functional differences in PSCs between normoxia (21% O2) and hypoxia (1% O2), including expression of various factors related to tumor-stromal interactions. We particularly analyzed effects on PC invasiveness of an overexpressed molecule-connective tissue growth factor (CTGF)-in PSCs under hypoxic conditions, using RNA interference techniques. Conditioned media from hypoxic PSCs enhanced PC cell invasiveness more intensely than that from normoxic PSCs (P cancer. Copyright © 2013 Elsevier Inc. All rights reserved.

Benchmarking pathway interaction network for colorectal cancer to identify dysregulated pathways

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Q. Wang

Full Text Available Different pathways act synergistically to participate in many biological processes. Thus, the purpose of our study was to extract dysregulated pathways to investigate the pathogenesis of colorectal cancer (CRC based on the functional dependency among pathways. Protein-protein interaction (PPI information and pathway data were retrieved from STRING and Reactome databases, respectively. After genes were aligned to the pathways, each pathway activity was calculated using the principal component analysis (PCA method, and the seed pathway was discovered. Subsequently, we constructed the pathway interaction network (PIN, where each node represented a biological pathway based on gene expression profile, PPI data, as well as pathways. Dysregulated pathways were then selected from the PIN according to classification performance and seed pathway. A PIN including 11,960 interactions was constructed to identify dysregulated pathways. Interestingly, the interaction of mRNA splicing and mRNA splicing-major pathway had the highest score of 719.8167. Maximum change of the activity score between CRC and normal samples appeared in the pathway of DNA replication, which was selected as the seed pathway. Starting with this seed pathway, a pathway set containing 30 dysregulated pathways was obtained with an area under the curve score of 0.8598. The pathway of mRNA splicing, mRNA splicing-major pathway, and RNA polymerase I had the maximum genes of 107. Moreover, we found that these 30 pathways had crosstalks with each other. The results suggest that these dysregulated pathways might be used as biomarkers to diagnose CRC.

Cigarette smoking, physical activity, and alcohol consumption as predictors of cancer incidence among women at high risk of breast cancer in the NSABP P-1 trial.

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Land, Stephanie R; Liu, Qing; Wickerham, D Lawrence; Costantino, Joseph P; Ganz, Patricia A

2014-05-01

NSABP P-1 provides an opportunity to examine the association of behavioral factors with prospectively monitored cancer incidence and interactions with tamoxifen. From 1992 to 1997, 13,388 women with estimated 5-year breast cancer risk greater than 1.66% or a history of lobular carcinoma in situ (87% younger than age 65; 67% postmenopausal) were randomly assigned to tamoxifen versus placebo. Invasive breast cancer, lung cancer, colon cancer, and endometrial cancer were analyzed with Cox regression. Predictors were baseline cigarette smoking, leisure-time physical activity, alcohol consumption, and established risk factors. At median 7 years follow-up, we observed 395, 66, 35, and 74 breast cancer, lung cancer, colon cancer, and endometrial cancer, respectively. Women who had smoked were at increased risk of breast cancer (P = 0.007; HR = 1.3 for 15-35 years smoking, HR = 1.6 for ≥ 35 years), lung cancer (P cancer (P breast cancer risk only among women assigned to placebo (P = 0.021 activity main effect, P = 0.013 activity-treatment interaction; HR = 1.4 for the placebo group) and endometrial cancer among all women (P = 0.026, HR = 1.7). Moderate alcohol (>0-1 drink/day) was associated with decreased risk of colon cancer (P = 0.019; HR = 0.35) versus no alcohol. There were no other significant associations between these behaviors and cancer risk. Among women with elevated risk of breast cancer, smoking has an even greater impact on breast cancer risk than observed in past studies in the general population. Women who smoke or are inactive should be informed of the increased risk of multiple types of cancer. ©2014 AACR.

Communication in cancer care: psycho-social, interactional, and cultural issues. A general overview and the example of India.

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Chaturvedi, Santosh K; Strohschein, Fay J; Saraf, Gayatri; Loiselle, Carmen G

2014-01-01

Communication is a core aspect of psycho-oncology care. This article examines key psychosocial, cultural, and technological factors that affect this communication. Drawing from advances in clinical work and accumulating bodies of empirical evidence, the authors identify determining factors for high quality, efficient, and sensitive communication and support for those affected by cancer. Cancer care in India is highlighted as a salient example. Cultural factors affecting cancer communication in India include beliefs about health and illness, societal values, integration of spiritual care, family roles, and expectations concerning disclosure of cancer information, and rituals around death and dying. The rapidly emerging area of e-health significantly impacts cancer communication and support globally. In view of current globalization, understanding these multidimensional psychosocial, and cultural factors that shape communication are essential for providing comprehensive, appropriate, and sensitive cancer care.

Communication in cancer care: Psycho social, interactional, and cultural issues. A general overview and the example of India

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SANTOSH K CHATURVEDI

2014-11-01

Full Text Available Communication is a core aspect of psycho-oncology care. This article examines key psychosocial, cultural, and technological factors that affect this communication. Drawing from advances in clinical work and accumulating bodies of empirical evidence, the authors identify determining factors for high quality, efficient, and sensitive communication and support for those affected by cancer. Cancer care in India is highlighted as a salient example. Cultural factors affecting cancer communication in India include beliefs about health and illness, societal values, integration of spiritual care, family roles, and expectations concerning disclosure of cancer information, and rituals around death and dying. The rapidly emerging area of e-health significantly impacts cancer communication and support globally. In view of current globalization, understanding these multidimensional psychosocial, and cultural factors that shape communication are essential for providing comprehensive, appropriate and sensitive cancer care.

Design principles for cancer therapy guided by changes in complexity of protein-protein interaction networks.

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Benzekry, Sebastian; Tuszynski, Jack A; Rietman, Edward A; Lakka Klement, Giannoula

2015-05-28

The ever-increasing expanse of online bioinformatics data is enabling new ways to, not only explore the visualization of these data, but also to apply novel mathematical methods to extract meaningful information for clinically relevant analysis of pathways and treatment decisions. One of the methods used for computing topological characteristics of a space at different spatial resolutions is persistent homology. This concept can also be applied to network theory, and more specifically to protein-protein interaction networks, where the number of rings in an individual cancer network represents a measure of complexity. We observed a linear correlation of R = -0.55 between persistent homology and 5-year survival of patients with a variety of cancers. This relationship was used to predict the proteins within a protein-protein interaction network with the most impact on cancer progression. By re-computing the persistent homology after computationally removing an individual node (protein) from the protein-protein interaction network, we were able to evaluate whether such an inhibition would lead to improvement in patient survival. The power of this approach lied in its ability to identify the effects of inhibition of multiple proteins and in the ability to expose whether the effect of a single inhibition may be amplified by inhibition of other proteins. More importantly, we illustrate specific examples of persistent homology calculations, which correctly predict the survival benefit observed effects in clinical trials using inhibitors of the identified molecular target. We propose that computational approaches such as persistent homology may be used in the future for selection of molecular therapies in clinic. The technique uses a mathematical algorithm to evaluate the node (protein) whose inhibition has the highest potential to reduce network complexity. The greater the drop in persistent homology, the greater reduction in network complexity, and thus a larger

Medical examination of A-bomb survivors on Nagasaki A-bomb Casualty

International Nuclear Information System (INIS)

Tagawa, Masuko

1996-01-01

Medical examination of A-bomb survivors was described and discussed on history, time change of examinee number, action for subjects not examined, change of prevalence, cancer examination, examination for the second generation, and education and enlightenment. Free examination of the survivors was begun in 1953 and the present casualty was made in 1958 on the law for medical care for the survivors. Systematic examination started from 1967 and the examination for the 2nd generation, from 1974. Cancer examination was from 1988. The number of the survivors was the maximum of 82,439 in 1974 and decreased to 61,388 in 1994, when the actual number of examinees, which being rather settled recently, was 32,294 and their average age was 64 y. The examination is done by tour or at the Center. Subjects receive the information of the examination twice by mail. Hematopoietic diseases like anemia, hepatic ones, metabolic and endocrinic ones like diabetes, renal impairment and others (mostly hyperlipidemia) are increasing recently. The number of examinees for cancer is increasing. Lung cancer is examined by the direct roentgenography, gastric cancer by transillumination, and other cancers like myeloma, those in large bowel, uterus and mammary gland, by the respective suitable methods. Health education and enlightenment have been conceivably effective. (H.O.)

MiR-27a rs895819 is involved in increased atrophic gastritis risk, improved gastric cancer prognosis and negative interaction with Helicobacter pylori

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Xu, Qian; Chen, Tie-jun; He, Cai-yun; Sun, Li-ping; Liu, Jing-wei; Yuan, Yuan

2017-01-01

MiR-27a rs895819 is a loop-stem structure single nucleotide polymorphism affecting mature miR-27a function. In this study, we performed a comprehensive analysis about the association of rs895819 with gastric cancer risk and prognosis, atrophic gastritis risk, as well as the interactions with environmental factors. A total of 939 gastric cancer patients, 1,067 atrophic gastritis patients and 1,166 healthy controls were screened by direct sequencing and MALDI-TOF-MS. The association of rs895819 with clinical pathological parameters and prognostic survival in 357 gastric cancer patients was also been analyzed. The rs895819 variant genotype increased the risk for atrophic gastritis (1.58-fold) and gastric cancer (1.24-fold). While in stratified analysis, the risk effect was demonstrated more significantly in the female, age >60y, Helicobacter pylori (H. pylori) negative and non-drinker subgroups. Rs895819 and H. pylori showed an interaction effect for atrophic gastritis risk. In the survival analysis, the rs895819 AG heterozygosis was associated with better survival than the AA wild-type in the TNM stage I–II subgroup. In vitro study by overexpressing miR-27a, cells carrying polymorphic-type G allele expressed lower miR-27a than wild-type A allele. In conclusion, miR-27a rs895819 is implicated as a biomarker for gastric cancer and atrophic gastritis risk, and interacts with H. pylori in gastric carcinogenesis. PMID:28150722

'End of life' conversations, appreciation sequences, and the interaction order in cancer clinics.

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Maynard, Douglas W; Cortez, Dagoberto; Campbell, Toby C

2016-01-01

To address the organization of conversations in oncology visits by taking an "interaction order" perspective and asking how these visits are intrinsically organized. Conversation analysis. Using audio recordings of talk in oncology visits involving patients with non-small cell lung cancer, we identify and analyze an "appreciation sequence" that is designed to elicit patients' understanding and positive assessment of treatments in terms of their prolongation of life. An "appreciation sequence," regularly initiated after the delivery of scan results and/or treatment recommendations, simultaneously reminds patients of their mortality while suggesting that the treatment received has prolonged their lives, and in some cases significantly beyond the median time of survival. We explore the functions of the appreciation sequence for cancer care and set the stage for considering where and when physicians have choices about the order and direction the talk can take and how to allocate time for end of life and quality of life conversations. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Subcellular analysis of interaction between breast cancer cells and drug by digital holography

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Zhao, Jie; Lin, Qiaowen; Wang, Dayong; Wang, Yunxin; Ouyang, Liting; Guo, Sha; Yao, Qian

2017-10-01

Digital holographic microscopy is a promising quantitative phase-contrast imaging technique, which exhibits the advantages of non-destruction, full field of view, quasi-real time, and don't need dye and external marker to the living biological sample. In this paper, the inverted off-axis image-plane digital holography with pre-magnification is built up to study the living MDA-MB-231 breast cancer cells. The lateral resolution of the proposed experimental setup is 0.87μm, which is verified by the standard USAF test target. Then the system is used to visualize the interaction between living breast cancer cells and drug. The blebbing is observed after the cells are treated by paclitaxel drug, and the distribution of the paclitaxel inside the cells is detected, which is near the cytomembrane, or in other words the end of the microtubules. It will stop the mitosis and cause the death of the cells. It is helpful to reveal the anticancer mechanism of paclitaxel in the subcellular scale.

Quantitative fluorescence nanoscopy for cancer biomedicine

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Huang, Tao; Nickerson, Andrew; Peters, Alec; Nan, Xiaolin

2015-08-01

Cancer is a major health threat worldwide. Options for targeted cancer therapy, however, are often limited, in a large part due to our incomplete understanding of how key processes including oncogenesis and drug response are mediated at the molecular level. New imaging techniques for visualizing biomolecules and their interactions at the nanometer and single molecule scales, collectively named fluorescence nanoscopy, hold the promise to transform biomedical research by providing direct mechanistic insight into cellular processes. We discuss the principles of quantitative single-molecule localization microscopy (SMLM), a subset of fluorescence nanoscopy, and their applications to cancer biomedicine. In particular, we will examine oncogenesis and drug resistance mediated by mutant Ras, which is associated with ~1/3 of all human cancers but has remained an intractable drug target. At ~20 nm spatial and single-molecule stoichiometric resolutions, SMLM clearly showed that mutant Ras must form dimers to activate its effector pathways and drive oncogenesis. SMLM further showed that the Raf kinase, one of the most important effectors of Ras, also forms dimers upon activation by Ras. Moreover, treatment of cells expressing wild type Raf with Raf inhibitors induces Raf dimer formation in a manner dependent on Ras dimerization. Together, these data suggest that Ras dimers mediate oncogenesis and drug resistance in tumors with hyperactive Ras and can potentially be targeted for cancer therapy. We also discuss recent advances in SMLM that enable simultaneous imaging of multiple biomolecules and their interactions at the nanoscale. Our work demonstrates the power of quantitative SMLM in cancer biomedicine.

Facets of Spirituality as Predictors of Adjustment to Cancer: Relative Contributions of Having Faith and Finding Meaning

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Yanez, Betina; Edmondson, Donald; Stanton, Annette L.; Park, Crystal L.; Kwan, Lorna; Ganz, Patricia A.; Blank, Thomas O.

2009-01-01

Spirituality is a multidimensional construct, and little is known about how its distinct dimensions jointly affect well-being. In longitudinal studies (Study 1, n = 418 breast cancer patients; Study 2, n = 165 cancer survivors), the authors examined 2 components of spiritual well-being (i.e., meaning/peace and faith) and their interaction, as well…

Health examination for A-bomb survivors

International Nuclear Information System (INIS)

Ito, Chikako

1996-01-01

The health examination for A-bomb survivors by national, prefectural and city administrations was described and discussed on its general concept, history, time change of examinee number, improvement of examination, prevalence of individual diseases, significance of cancer examinations, examinees' point of view and future problems. Subjects were the survivors living in Hiroshima city: in 1994, their number was 100,188, whose ages were 63 y in average for males consisting of 39.5% and 67 y for females of 60.5%. The examination was begun in 1957 on the law for medical care for the survivors firstly and then systematically in 1961. From 1965, it was performed 4 times a year, and in 1988, one examination in the four was made for cancer. Authors' Center examined previously 90% but recently 70% of the examinees. The remainder underwent the examination in other medical facilities. Tests are blood analysis, electrocardiography and computed radiography of chest with imaging plate, of which data have been accumulated either in photodisc or in host computer. From 1973 to 1993, the cardiovascular diseases increased from 6.1% to 26.9%, metabolic and endocrinic ones like diabetes, 3.6% to 19.7%, and bowel ones, 0.9% to 12.3%. Correlations of these diseases with A-bomb irradiation are not elucidated and possibly poor. Five classes of cancer examinations are performed but the examinee rate in the survivors is as low as 7.6-21.8% (1993). The cancer of the large intestine is increasing. The overall examinee rates in the survivors were 70.6% in 1965-1967, 69.5% in 1976-1977 and 58.2% in 1990. In conclusion, how to examine the survivors, who are getting older, as many as possible is the future problem. (H.O.)

How Can We Treat Cancer Disease Not Cancer Cells?

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Kim, Kyu-Won; Lee, Su-Jae; Kim, Woo-Young; Seo, Ji Hae; Lee, Ho-Young

2017-01-01

Since molecular biology studies began, researches in biological science have centered on proteins and genes at molecular level of a single cell. Cancer research has also focused on various functions of proteins and genes that distinguish cancer cells from normal cells. Accordingly, most contemporary anticancer drugs have been developed to target abnormal characteristics of cancer cells. Despite the great advances in the development of anticancer drugs, vast majority of patients with advanced cancer have shown grim prognosis and high rate of relapse. To resolve this problem, we must reevaluate our focuses in current cancer research. Cancer should be considered as a systemic disease because cancer cells undergo a complex interaction with various surrounding cells in cancer tissue and spread to whole body through metastasis under the control of the systemic modulation. Human body relies on the cooperative interaction between various tissues and organs, and each organ performs its specialized function through tissue-specific cell networks. Therefore, investigation of the tumor-specific cell networks can provide novel strategy to overcome the limitation of current cancer research. This review presents the limitations of the current cancer research, emphasizing the necessity of studying tissue-specific cell network which could be a new perspective on treating cancer disease, not cancer cells.

YouTube as a source of information on mouth (oral) cancer.

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Hassona, Y; Taimeh, D; Marahleh, A; Scully, C

2016-04-01

We examined the content of YouTube(™) videos on mouth (oral) cancer and evaluated their usefulness in promoting early detection of oral cancer. A systematic search of YouTube(™) for videos containing information on mouth cancer was conducted using the keywords 'mouth cancer' and 'oral cancer'. Demographics of videos, including type, source, length, and viewers' interaction, were evaluated, and three researchers independently assessed the videos for usefulness in promoting early detection of oral cancer. A total of 188 YouTube(™) videos (152 patient-oriented educational videos and 36 testimonial videos) were analyzed. The overall usefulness score ranged from 0 to 10 (mean = 3.56 ± 2.44). The most useful videos ranked late on the viewing list, and there was no significant correlation between video usefulness and viewing rate, viewers' interaction, and video length. Videos uploaded by individual users were less useful compared with videos uploaded by professional organizations or by healthcare professionals. Healthcare professionals, academic institutions, and professional organizations have a responsibility for improving the content of YouTube(™) about mouth cancer by uploading useful videos, and directing patients to reliable information sources. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.