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Sample records for multiple colorectal cancer

  1. BRAF mutation in multiple primary cancer with colorectal cancer and stomach cancer

    PubMed Central

    Lee, Seung-Hyun; Ahn, Byung-Kwon; Baek, Sung-Uhn; Chang, Hee-Kyung

    2013-01-01

    Aims: Recently, BRAF mutation testing has been introduced as a marker in differentiating Lynch syndrome from sporadic colorectal cancers or in predicting colorectal cancers with worse prognosis. Individuals with hereditary predisposition to cancer development are at an increased risk of developing multiple primary cancers. The purpose of this study is to identify mutation in the BRAF gene in multiple primary cancers with colorectal cancer and stomach cancer. Methods: BRAF mutation was analysed in 45 patients with colorectal cancer and stomach cancer, synchronously or metachronously. Results: Mean age was 64.07 years (range: 47–83 years). For the colorectal cancer, tumors were located at the sigmoid colon in eight patients (17.8%) and at the rectum in 22 patients (48.9%). Twenty-three patients (51.1%) had synchronous cancer. Four patients (8.9%) had family members with cancer. BRAF mutation was identified in three patients (6.7%). All three of these patients had metachronous cancers. The colorectal cancers were located in the sigmoid colon (1 patient) and the rectum (2 patients). Conclusions: BRAF mutation rate was low in the multiple primary cancer with colorectal cancer and stomach cancer. With only BRAF gene study, it was not possible to identify any correlation with family history of colorectal cancer. Further study means considering other genes – MSI, MSH2, MLH1, MSH6. PMID:24759670

  2. Colorectal Cancer - Multiple Languages: MedlinePlus

    MedlinePlus

    ... سرطان القولون والمستقيم - العربية Bilingual PDF Health Information Translations Hemoccult Test (Arabic) اختبار الدم الخفي في البراز - العربية Bilingual PDF Health Information Translations Bosnian (Bosanski) Cancer of the Colon and Rectum ...

  3. Colorectal Cancer

    MedlinePlus

    ... rectum are part of the large intestine. Colorectal cancer occurs when tumors form in the lining of ... men and women. The risk of developing colorectal cancer rises after age 50. You're also more ...

  4. Multiple Sporadic Colorectal Cancers Display a Unique Methylation Phenotype

    PubMed Central

    Gonzalo, Victoria; Lozano, Juan Jose; Alonso-Espinaco, Virginia; Moreira, Leticia; Muñoz, Jenifer; Pellisé, Maria; Castellví-Bel, Sergi; Bessa, Xavier; Andreu, Montserrat; Xicola, Rosa M.; Llor, Xavier; Ruiz-Ponte, Clara; Carracedo, Angel; Jover, Rodrigo; Castells, Antoni; Balaguer, Francesc

    2014-01-01

    Epigenetics are thought to play a major role in the carcinogenesis of multiple sporadic colorectal cancers (CRC). Previous studies have suggested concordant DNA hypermethylation between tumor pairs. However, only a few methylation markers have been analyzed. This study was aimed at describing the epigenetic signature of multiple CRC using a genome-scale DNA methylation profiling. We analyzed 12 patients with synchronous CRC and 29 age-, sex-, and tumor location-paired patients with solitary tumors from the EPICOLON II cohort. DNA methylation profiling was performed using the Illumina Infinium HM27 DNA methylation assay. The most significant results were validated by Methylight. Tumors samples were also analyzed for the CpG Island Methylator Phenotype (CIMP); KRAS and BRAF mutations and mismatch repair deficiency status. Functional annotation clustering was performed. We identified 102 CpG sites that showed significant DNA hypermethylation in multiple tumors with respect to the solitary counterparts (difference in β value ≥0.1). Methylight assays validated the results for 4 selected genes (p = 0.0002). Eight out of 12(66.6%) multiple tumors were classified as CIMP-high, as compared to 5 out of 29(17.2%) solitary tumors (p = 0.004). Interestingly, 76 out of the 102 (74.5%) hypermethylated CpG sites found in multiple tumors were also seen in CIMP-high tumors. Functional analysis of hypermethylated genes found in multiple tumors showed enrichment of genes involved in different tumorigenic functions. In conclusion, multiple CRC are associated with a distinct methylation phenotype, with a close association between tumor multiplicity and CIMP-high. Our results may be important to unravel the underlying mechanism of tumor multiplicity. PMID:24643221

  5. Multiple primary colorectal cancer: Individual or familial predisposition?

    PubMed Central

    Pajares, José A; Perea, José

    2015-01-01

    Colorectal carcinoma (CRC) is one of the most frequent cancers. Along the surface of the large bowel, several foci of CRC may appear simultaneously or over the time. The development of at least two different tumours has been defined as multiple primary CRC (MPCRC): When more than one tumour is diagnosed at the same time, it is known as synchronous CRC (SCRC), while when a second neoplasm is diagnosed some time after the resection and/or diagnosis of the first lesion, it is called metachronous CRC (MCRC). Multiple issues can promote the development of MPCRC, ranging from different personal factors, such as environmental exposure, to familial predisposition due to hereditary factors. However, most studies do not distinguish this dichotomy. High- and low-pentrance genetic variants are involved in MPCRC. An increased risk for MPCRC has been described in Lynch syndrome, familial adenomatous polyposis, and serrated polyposis. Non-syndromic familial CRCs should also be considered as risk factors for MPCRC. Environmental factors can promote damage to colon mucosae that enable the concurrence of MPCRC. Epigenetics are thought to play a major role in the carcinogenesis of sporadic MPCRC. The methylation state of the DNA depends on multiple environmental factors (e.g., smoking and eating foods cooked at high temperatures), and this can contribute to increasing the MPCRC rate. Certain clinical features may also suggest individual predisposition for MPCRC. Different etiopathogenic factors are suspected to be involved in SCRC and MCRC, and different familial vs individual factors may be implicated. MCRC seems to follow a familial pattern, whereas individual factors are more important in SCRC. Further studies must be carried out to know the molecular basis of risks for MPCRC in order to modify, if necessary, its clinical management, especially from a preventive point of view. PMID:26688706

  6. Multiple primary colorectal cancer: Individual or familial predisposition?

    PubMed

    Pajares, José A; Perea, José

    2015-12-15

    Colorectal carcinoma (CRC) is one of the most frequent cancers. Along the surface of the large bowel, several foci of CRC may appear simultaneously or over the time. The development of at least two different tumours has been defined as multiple primary CRC (MPCRC): When more than one tumour is diagnosed at the same time, it is known as synchronous CRC (SCRC), while when a second neoplasm is diagnosed some time after the resection and/or diagnosis of the first lesion, it is called metachronous CRC (MCRC). Multiple issues can promote the development of MPCRC, ranging from different personal factors, such as environmental exposure, to familial predisposition due to hereditary factors. However, most studies do not distinguish this dichotomy. High- and low-pentrance genetic variants are involved in MPCRC. An increased risk for MPCRC has been described in Lynch syndrome, familial adenomatous polyposis, and serrated polyposis. Non-syndromic familial CRCs should also be considered as risk factors for MPCRC. Environmental factors can promote damage to colon mucosae that enable the concurrence of MPCRC. Epigenetics are thought to play a major role in the carcinogenesis of sporadic MPCRC. The methylation state of the DNA depends on multiple environmental factors (e.g., smoking and eating foods cooked at high temperatures), and this can contribute to increasing the MPCRC rate. Certain clinical features may also suggest individual predisposition for MPCRC. Different etiopathogenic factors are suspected to be involved in SCRC and MCRC, and different familial vs individual factors may be implicated. MCRC seems to follow a familial pattern, whereas individual factors are more important in SCRC. Further studies must be carried out to know the molecular basis of risks for MPCRC in order to modify, if necessary, its clinical management, especially from a preventive point of view.

  7. Inherited Colorectal Cancer Syndromes

    PubMed Central

    Kastrinos, Fay; Syngal, Sapna

    2011-01-01

    Colorectal cancer is the most common gastrointestinal malignancy and the second leading cause of cancer death in both men and women in the United States. Most colorectal cancer cases diagnosed annually are due to sporadic events but up to 5% are attributed to known monogenic disorders including Lynch syndrome, Familial Adenomatous Polyposis, MYH-associated polyposis, and the rare hamartomatous polyposis syndromes. These inherited colorectal cancer syndromes confer a markedly increased risk for the development of multiple cancers and predictive genetic testing is available to identify mutation carriers and at-risk family members. Through personalized strategies for diagnosis and management, a substantial reduction in morbidity and mortality has been appreciated among patients at highest risk for the development of colorectal cancer. PMID:22157284

  8. Common colorectal cancer risk alleles contribute to the multiple colorectal adenoma phenotype, but do not influence colonic polyposis in FAP

    PubMed Central

    Cheng, Timothy H T; Gorman, Maggie; Martin, Lynn; Barclay, Ella; Casey, Graham; Newcomb, Polly A; Casey, Graham; Conti, David V; Schumacher, Fred; Gallinger, Steve; Lindor, Noralane M; Hopper, John; Jenkins, Mark; Hunter, David J; Kraft, Peter; Jacobs, Kevin B; Cox, David G; Yeager, Meredith; Hankinson, Susan E; Wacholder, Sholom; Wang, Zhaoming; Welch, Robert; Hutchinson, Amy; Wang, Junwen; Yu, Kai; Chatterjee, Nilanjan; Orr, Nick; Willett, Walter C; Colditz, Graham A; Ziegler, Regina G; Berg, Christine D; Buys, Saundra S; McCarty, Catherine A; Feigelson, Heather Spencer; Calle, Eugenia E; Thun, Michael J; Hayes, Richard B; Tucker, Margaret; Gerhard, Daniela S; Fraumeni, Joseph F; Hoover, Robert N; Thomas, Gilles; Chanock, Stephen J; Yeager, Meredith; Chatterjee, Nilanjan; Ciampa, Julia; Jacobs, Kevin B; Gonzalez-Bosquet, Jesus; Hayes, Richard B; Kraft, Peter; Wacholder, Sholom; Orr, Nick; Berndt, Sonja; Yu, Kai; Hutchinson, Amy; Wang, Zhaoming; Amundadottir, Laufey; Feigelson, Heather Spencer; Thun, Michael J; Diver, W Ryan; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie; Schumacher, Fredrick R; Cancel-Tassin, Geraldine; Cussenot, Olivier; Valeri, Antoine; Andriole, Gerald L; Crawford, E David; Haiman, Christopher A; Henderson, Brian; Kolonel, Laurence; Marchand, Loic Le; Siddiq, Afshan; Riboli, Elio; Key, Timothy J; Kaaks, Rudolf; Isaacs, William; Isaacs, Sarah; Wiley, Kathleen E; Gronberg, Henrik; Wiklund, Fredrik; Stattin, Pär; Xu, Jianfeng; Zheng, S Lilly; Sun, Jielin; Vatten, Lars J; Hveem, Kristian; Kumle, Merethe; Tucker, Margaret; Gerhard, Daniela S; Hoover, Robert N; Fraumeni, Joseph F; Hunter, David J; Thomas, Gilles; Chanock, Stephen J; Purdue, Mark P; Johansson, Mattias; Zelenika, Diana; Toro, Jorge R; Scelo, Ghislaine; Moore, Lee E; Prokhortchouk, Egor; Wu, Xifeng; Kiemeney, Lambertus A; Gaborieau, Valerie; Jacobs, Kevin B; Chow, Wong-Ho; Zaridze, David; Matveev, Vsevolod; Lubinski, Jan; Trubicka, Joanna; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Rudnai, Péter; Fabianova, Eleonora; Bucur, Alexandru; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Boffetta, Paolo; Colt, Joanne S; Davis, Faith G; Schwartz, Kendra L; Banks, Rosamonde E; Selby, Peter J; Harnden, Patricia; Berg, Christine D; Hsing, Ann W; Grubb III, Robert L; Boeing, Heiner; Vineis, Paolo; Clavel-Chapelon, Françoise; Palli, Domenico; Tumino, Rosario; Krogh, Vittorio; Panico, Salvatore; Duell, Eric J; Quirós, José Ramón; Sanchez, Maria-José; Navarro, Carmen; Ardanaz, Eva; Dorronsoro, Miren; Khaw, Kay-Tee; Allen, Naomi E; Bueno-de-Mesquita, H Bas; Peeters, Petra H M; Trichopoulos, Dimitrios; Linseisen, Jakob; Ljungberg, Börje; Overvad, Kim; Tjønneland, Anne; Romieu, Isabelle; Riboli, Elio; Mukeria, Anush; Shangina, Oxana; Stevens, Victoria L; Thun, Michael J; Diver, W Ryan; Gapstur, Susan M; Pharoah, Paul D; Easton, Douglas F; Albanes, Demetrius; Weinstein, Stephanie J; Virtamo, Jarmo; Vatten, Lars; Hveem, Kristian; Njølstad, Inger; Tell, Grethe S; Stoltenberg, Camilla; Kumar, Rajiv; Koppova, Kvetoslava; Cussenot, Olivier; Benhamou, Simone; Oosterwijk, Egbert; Vermeulen, Sita H; Aben, Katja K H; van der Marel, Saskia L; Ye, Yuanqing; Wood, Christopher G; Pu, Xia; Mazur, Alexander M; Boulygina, Eugenia S; Chekanov, Nikolai N; Foglio, Mario; Lechner, Doris; Gut, Ivo; Heath, Simon; Blanche, Hélène; Hutchinson, Amy; Thomas, Gilles; Wang, Zhaoming; Yeager, Meredith; Fraumeni, Joseph F; Skryabin, Konstantin G; McKay, James D; Rothman, Nathaniel; Chanock, Stephen J; Lathrop, Mark; Brennan, Paul; Saunders, Brian; Thomas, Huw; Clark, Sue; Tomlinson, Ian

    2015-01-01

    The presence of multiple (5–100) colorectal adenomas suggests an inherited predisposition, but the genetic aetiology of this phenotype is undetermined if patients test negative for Mendelian polyposis syndromes such as familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP). We investigated whether 18 common colorectal cancer (CRC) predisposition single-nucleotide polymorphisms (SNPs) could help to explain some cases with multiple adenomas who phenocopied FAP or MAP, but had no pathogenic APC or MUTYH variant. No multiple adenoma case had an outlying number of CRC SNP risk alleles, but multiple adenoma patients did have a significantly higher number of risk alleles than population controls (P=5.7 × 10−7). The association was stronger in those with ≥10 adenomas. The CRC SNPs accounted for 4.3% of the variation in multiple adenoma risk, with three SNPs (rs6983267, rs10795668, rs3802842) explaining 3.0% of the variation. In FAP patients, the CRC risk score did not differ significantly from the controls, as we expected given the overwhelming effect of pathogenic germline APC variants on the phenotype of these cases. More unexpectedly, we found no evidence that the CRC SNPs act as modifier genes for the number of colorectal adenomas in FAP patients. In conclusion, common colorectal tumour risk alleles contribute to the development of multiple adenomas in patients without pathogenic germline APC or MUTYH variants. This phenotype may have ‘polygenic' or monogenic origins. The risk of CRC in relatives of multiple adenoma cases is probably much lower for cases with polygenic disease, and this should be taken into account when counselling such patients. PMID:24801760

  9. 6 Common Cancers - Colorectal Cancer

    MedlinePlus

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Colorectal Cancer Past Issues / Spring 2007 Table of Contents For ... colon cancer. Photo: AP Photo/Ron Edmonds Colorectal Cancer Cancer of the colon (large intestine) or rectum ( ...

  10. Colorectal Cancer Prevention

    MedlinePlus

    ... Genetics of Colorectal Cancer Colorectal cancer is the second leading cause of death from cancer in the ... professional versions have detailed information written in technical language. The patient versions are written in easy-to- ...

  11. Five Myths about Colorectal Cancer

    MedlinePlus

    ... ACS » Your Local Offices Close + - Text Size Five Myths About Colorectal Cancer In many cases, colorectal cancer ... screening tests you need, when you need them. Myth: Colorectal cancer is a man’s disease. Truth: Colorectal ...

  12. Synchronous trifocal colorectal cancer

    PubMed Central

    Charalampoudis, Petros; Kykalos, Stylianos; Stamopoulos, Paraskevas; Kouraklis, Gregory

    2016-01-01

    Synchronous colorectal cancers (SCRCs) have been increasingly diagnosed due to emerging diagnostic modalities. The presence of three or more synchronous colorectal cancers has, however, only rarely been reported. A 76-year-old white man presented for management of two concurrent colorectal adenocarcinomas in the left colon evidenced on total colonoscopy. Preoperative abdominal ultrasonography and thoracoabdominal computed tomography were negative for metastatic disease. The patient underwent an elective left hemicolectomy. The pathology report ultimately showed the presence of three moderately differentiated, distinct colorectal cancers. The patient experienced an uneventful recovery. PMID:27695171

  13. Synchronous trifocal colorectal cancer

    PubMed Central

    Charalampoudis, Petros; Kykalos, Stylianos; Stamopoulos, Paraskevas; Kouraklis, Gregory

    2016-01-01

    Synchronous colorectal cancers (SCRCs) have been increasingly diagnosed due to emerging diagnostic modalities. The presence of three or more synchronous colorectal cancers has, however, only rarely been reported. A 76-year-old white man presented for management of two concurrent colorectal adenocarcinomas in the left colon evidenced on total colonoscopy. Preoperative abdominal ultrasonography and thoracoabdominal computed tomography were negative for metastatic disease. The patient underwent an elective left hemicolectomy. The pathology report ultimately showed the presence of three moderately differentiated, distinct colorectal cancers. The patient experienced an uneventful recovery.

  14. Chemoprevention of colorectal cancer.

    PubMed

    Lang, Michaela; Gasche, Christoph

    2015-01-01

    Colorectal cancer has become one of the most prevalent malignant diseases for both men and women. Patients with inflammatory bowel diseases or certain inherited cancer syndromes are at high risk of developing colorectal cancer and have naturally the highest need for cancer prevention. In familial adenomatous polyposis (FAP) and Lynch syndrome, most of the underlying germline mutations can be detected by DNA sequencing, and medical counselling of affected individuals involves both surveillance tests and chemopreventive measures. However, as the mechanisms leading to colorectal cancer differ in these high-risk groups, the molecular action of chemopreventive drugs needs to be adjusted to the certain pathway of carcinogenesis. In the last decades, a number of drugs have been tested, including sulindac, aspirin, celecoxib, and mesalazine, but some of them are still controversially discussed. This review summarizes the advances and current standards of colorectal cancer prevention in patients with inflammatory bowel disease, FAP and Lynch syndrome. PMID:25531498

  15. Oleanolic acid modulates multiple intracellular targets to inhibit colorectal cancer growth.

    PubMed

    Li, Li; Wei, Lihui; Shen, Aling; Chu, Jianfeng; Lin, Jiumao; Peng, Jun

    2015-12-01

    Due to drug resistance and unacceptable cytotoxicity of most currently-used cancer chemotherapies, naturally occurring products have gained attention in the field of anticancer treatment. Oleanolic acid (OA) is a natural pentacyclic triterpenoic acid and a principal active compound in many medicinal herbs that have long been used to clinically treat various types of human malignancies. Using a colorectal cancer (CRC) mouse xenograft model and the cell line HT-29, we evaluated the effect of OA on tumor growth in vivo and in vitro, and investigated the underlying molecular mechanisms in the present study. We found that OA significantly inhibited tumor growth in volume and weight in CRC xenograft mice. In addition, OA treatment led to the induction of apoptosis and inhibition of cell proliferation. OA significantly reduced the expression of Bcl-2, Cyclin D1 and CKD4, whereas Bax and p21 expression was profoundly increased after OA treatment. Furthermore, OA significantly suppressed the activation of Akt, p70S6K and MAPK signalings, but promoted p53 pathway activation. Collectively, findings from this study suggest that OA possesses a broad range of anticancer effects via modulation of multiple intracellular targets. PMID:26459864

  16. Epidemiology of colorectal cancer

    PubMed Central

    Marley, Andrew R; Nan, Hongmei

    2016-01-01

    Colorectal cancer is currently the third deadliest cancer in the United States and will claim an estimated 49,190 U.S. lives in 2016. The purpose of this review is to summarize our current understanding of this disease, based on nationally published statistics and information presented in peer-reviewed journal articles. Specifically, this review will cover the following topics: descriptive epidemiology (including time and disease trends both in the United States and abroad), risk factors (environmental, genetic, and gene-environment interactions), screening, prevention and control, and treatment. Landmark discoveries in colorectal cancer risk factor research will also be presented. Based on the information reviewed for this report, we suggest that future U.S. public health efforts aim to increase colorectal cancer screening among African American communities, and that future worldwide colorectal cancer epidemiology studies should focus on researching nutrient-gene interactions towards the goal of improving personalized treatment and prevention strategies. PMID:27766137

  17. Risks of Colorectal Cancer Screening

    MedlinePlus

    ... Genetics of Colorectal Cancer Colorectal cancer is the second leading cause of death from cancer in the ... professional versions have detailed information written in technical language. The patient versions are written in easy-to- ...

  18. Tests for Colorectal Cancer

    MedlinePlus

    ... to look for colorectal cancer Imaging tests use sound waves, x-rays, magnetic fields, or radioactive substances to ... has spread to the liver. Ultrasound Ultrasound uses sound waves and their echoes to create images of the ...

  19. The prognostic factors and multiple biomarkers in young patients with colorectal cancer

    PubMed Central

    Wang, Mo-Jin; Ping, Jie; Li, Yuan; Adell, Gunnar; Arbman, Gunnar; Nodin, Bjorn; Meng, Wen-Jian; Zhang, Hong; Yu, Yong-Yang; Wang, Cun; Yang, Lie; Zhou, Zong-Guang; Sun, Xiao-Feng

    2015-01-01

    The incidence of colorectal cancer (CRC) in young patients (≤50 years of age) appears to be increasing. However, their clinicopathological characteristics and survival are controversial. Likewise, the biomarkers are unclear. We used the West China (2008-2013, China), Surveillance, Epidemiology, and End Results program (1973-2011, United States) and Linköping Cancer (1972-2009, Sweden) databases to analyse clinicopathological characteristics, survival and multiple biomarkers of young CRC patients. A total of 509,934 CRC patients were included from the three databases. The young CRC patients tended to have more distal location tumours, fewer tumour numbers, later stage, more mucinous carcinoma and poorer differentiation. The cancer-specific survival (CSS) of young patients was significantly better. The PRL (HR = 12.341, 95% CI = 1.615-94.276, P = 0.010), RBM3 (HR = 0.093, 95% CI = 0.012-0.712, P = 0.018), Wrap53 (HR = 1.952, 95% CI = 0.452-6.342, P = 0.031), p53 (HR = 5.549, 95% CI = 1.176-26.178, P = 0.045) and DNA status (HR = 17.602, 95% CI = 2.551-121.448, P = 0.001) were associated with CSS of the young patients. In conclusion, this study suggests that young CRC patients present advanced tumours and more malignant pathological features, while they have a better prognosis. The PRL, RBM3, Wrap53, p53 and DNA status are potential prognostic biomarkers for the young CRC patients. PMID:26013439

  20. Vitamin and multiple-vitamin supplement intake and incidence of colorectal cancer: a meta-analysis of cohort studies.

    PubMed

    Liu, Yan; Yu, Qiuyan; Zhu, Zhenli; Zhang, Jun; Chen, Meilan; Tang, Pingyi; Li, Ke

    2015-01-01

    This paper systematically evaluated the association of intake of different vitamins and multiple-vitamin supplements and the incidence of colorectal cancer. Relevant studies were identified in MEDLINE via PubMed (published up to April 2014). We extracted data from articles on vitamins A, C, D, E, B9 (folate), B2, B3, B6, and B12 and multiple-vitamin supplements. We used multivariable-adjusted relative risks (RRs) and a random-effects model for analysis and random effects. With heterogeneity, we looked for the source of heterogeneity or performed sensitivity and stratified analyses. We found 47 articles meeting the inclusion criteria. The multivariable-adjusted RR for pooled studies for the association between the highest versus lowest vitamin B9 (folate) intake and colorectal cancer was 0.88 [95 % confidence interval (95 % CI) 0.81-0.95]. Vitamin D was 0.87 (95 % CI 0.77-0.99); vitamin B6, 0.88 (95 % CI 0.79-0.99); vitamin B2, 0.86 (95 % CI, 0.76-0.97); vitamin A, 0.87 (95 % CI, 0.75-1.03); vitamin C, 0.92 (95 % CI, 0.80-1.06); vitamin E, 0.94 (95 % CI, 0.82-1.07); vitamin B12, 1.10 (95 % CI, 0.92-1.32); vitamin B3, 1.18 (95 % CI, 0.76-1.84). Vitamin B9 (folate), D, B6, and B2 intake was inversely associated with risk of colorectal cancer, but further study is needed. Our study featured unacceptable heterogeneity for studies of multiple-vitamin supplements, so findings were inconclusive.

  1. The Mendelian colorectal cancer syndromes

    PubMed Central

    2015-01-01

    A small minority of colorectal cancers (CRCs) (≤5%) are caused by a single, inherited faulty gene. These diseases, the Mendelian colorectal cancer (CRC) syndromes, have been central to our understanding of colorectal carcinogenesis in general. Most of the approximately 13 high-penetrance genes that predispose to CRC primarily predispose to colorectal polyps, and each gene is associated with a specific type of polyp, whether conventional adenomas (APC, MUTYH, POLE, POLD1, NTHL1), juvenile polyps (SMAD4, BMPR1A), Peutz-Jeghers hamartomas (LKB1/STK11) and mixed polyps of serrated and juvenile types (GREM1). Lynch syndrome (MSH2, MLH1, MSH6, PMS2), by contrast, is associated primarily with cancer risk. Major functional pathways are consistently inactivated in the Mendelian CRC syndromes: certain types of DNA repair (proofreading of DNA replication errors, mismatch repair and base excision repair) and signalling (bone morphogenetic protein (BMP), Wnt signalling and mTOR). The inheritance of the CRC syndromes also varies: most are dominant but some of the DNA repair deficiencies are recessive. Some of the Mendelian CRC genes are especially important because they play a role through somatic inactivation in sporadic CRC (APC, MLH1, SMAD4, POLE). Additional Mendelian CRC genes may remain to be discovered and searches for these genes are ongoing, especially in patients with multiple adenomas and hyperplastic polyps. PMID:26169059

  2. [Nutrition and colorectal cancer].

    PubMed

    Ströhle, Alexander; Maike, Wolters; Hahn, Andreas

    2007-01-01

    Diet plays an important role in the pathogenesis of colorectal cancer. Current prospective cohort studies and metaanalysis enable a reevaluation of how food or nutrients such as fiber and fat influence cancer risk. Based on the evidence criteria of the WHO/FAD, risk reduction by a high intake of fruit is assessed as possible, while a lowered risk by a high vegetable intake is probable. Especially raw vegetables and fruits seem to exert anticancer properties. The evidence of a risk reducing effect of whole grain relating to colorectal cancer is assessed as probable whereas the evidence of an increased risk by high consumption of refined white flour products and sweets is (still) insufficient despite some evidences. There is a probable risk reducing effect of milk and dairy products. e available data on eggs and red meat indicate a possible risk increasing influence. Stronger clues for a risk increasing effect have been shown for meat products leading to an evidence assessed as probable. Owing to varied interpretations of the data on fiber, the evidence of a risk reducing effect relating to colorectal cancer is assessed as possible or insufficient. The available data on alcohol consumption indicate a possible risk increasing effect. In contrast to former evaluations, diets rich in fat seem to increase colorectal cancer risk only indirectly as part of a hypercaloric diet by advancing the obesity risk. Thus, the evidence of obesity, especially visceral obesity, as a risk of colorectal cancer is judged as convincing today. Prospective cohort studies suggest that people who get higher than average amounts of folic acid from multivitamin supplements have lower risks of colorectal cancer. The evidence for a risk reducing effect of calcium, selenium, vitamin D and vitamin E on colorectal cancer is insufficient. As primary prevention, a diet rich in vegetables, fruits, whole grain products, and legumes added by low-fat dairy products, fish, and poultry can be recommended. In

  3. Radioimmunodetection of colorectal cancer

    SciTech Connect

    Kim, E.E.; Deland, F.H.; Casper, S.; Corgan, R.L.; Primus, F.J.; Goldenberg, D.M.

    1980-03-15

    This study examines the accuracy of colorectal cancer radioimmunodetection. Twenty-seven patients with a history of histologically-confirmed colonic or rectal carcinoma received a high-titer, purified goat anti-CEA IgG labelled with /sup 131/I at a total dose of at least 1.0 ..mu..Ci. Various body views were scanned at 24 and 48 hours after administration of the radioantibody. Three additional cases were evaluated; one had a villous adenoma in the rectum and received the /sup 131/I-labeled anti-CEA IgG, while two colonic carcinoma patients received normal goat IgG labelled with /sup 131/I. All of the 7 cases with primary colorectal cancer showed true-positive tumor localization, while 20 of 25 sites of metastatic colorectal cancer detected by immune scintigraphy were corroborated by other detection measures. The sensitivity of the radioimmunodetection of colorectal cancers (primary and metastatic) was found to be 90% (true-positive rate), the putative specificity (true-negative rate) was 94%, and the apparent overall accuracy of the technique was 93%. Neither the case of a villous adenoma receiving the anti-CEA IgG nor the two cases of colonic cancer receiving normal goat IgG showed tumor radiolocalization. Very high circulating CEA titers did not appear to hinder successful tumor radiolocalization. These findings suggest that in colorectal cancers the method of CEA radioimmunodetection may be of value in preoperatively determining the location and extent of disease, in assessing possible recurrence or spread postoperatively, and in localizing the source of CEA production in patients with rising or elevated CEA titers. An ancilliary benefit could be a more tumor-specific detection test for confirming the findings of other, more conventional diagnostic measures.

  4. Radioimmunodetection of colorectal cancer.

    PubMed

    Kim, E E; Deland, F H; Casper, S; Corgan, R L; Primus, F J; Goldenberg, D M

    1980-03-15

    This study examines the accuracy of colorectal cancer radioimmunodetection. Twenty-seven patients with a history of histologically-confirmed colonic or rectal carcinoma received a high-titer, purified goat anti-CEA IgG labelled with 131-I at a total dose of at least 1.0 muCi. Various body views were scanned at 24 and 48 hours after administration of the radioantibody. Three additional cases were evaluated; one had a villous adenoma in the rectum and received the 131-I-labelled anti-CEA IgG, while two colonic carcinoma patients received normal goat IgG labelled with 131-I. All of the 7 cases with primary colorectal cancer showed true-positive tumor localization, while 20 of 25 sites of metastatic colorectal cancer detected by immune scintigraphy were corroborated by other detection measures. The sensitivity of the radioimmunodetection of colorectal cancers (primary and metastatic) was found to be 90% (true-positive rate), the putative specificity (true-negative rate) was 94%, and the appraent overall accuracy of the technique was 93%. Neither the case of a villous adenoma receiving the anti-CEA IgG nor the two cases of colonic cancer receiving normal goat IgG showed tumor radiolocalization. Very high circulating CEA titers did not appear to hinder successful tumor radiolocalization. These findings suggest that in colorectal cancers the method of CEA radioimmunodetection may be of value in preoperatively determining the location and extent of disease, in assessing possible recurrence or spread postoperatively, and in localizing the source of CEA production in patients with rising or elevated CEA titers. An ancilliary benefit could be a more tumor-specific detection test for confirming the findings of other, more conventional diagnostic measures.

  5. Connectivity mapping using a combined gene signature from multiple colorectal cancer datasets identified candidate drugs including existing chemotherapies

    PubMed Central

    2015-01-01

    Background While the discovery of new drugs is a complex, lengthy and costly process, identifying new uses for existing drugs is a cost-effective approach to therapeutic discovery. Connectivity mapping integrates gene expression profiling with advanced algorithms to connect genes, diseases and small molecule compounds and has been applied in a large number of studies to identify potential drugs, particularly to facilitate drug repurposing. Colorectal cancer (CRC) is a commonly diagnosed cancer with high mortality rates, presenting a worldwide health problem. With the advancement of high throughput omics technologies, a number of large scale gene expression profiling studies have been conducted on CRCs, providing multiple datasets in gene expression data repositories. In this work, we systematically apply gene expression connectivity mapping to multiple CRC datasets to identify candidate therapeutics to this disease. Results We developed a robust method to compile a combined gene signature for colorectal cancer across multiple datasets. Connectivity mapping analysis with this signature of 148 genes identified 10 candidate compounds, including irinotecan and etoposide, which are chemotherapy drugs currently used to treat CRCs. These results indicate that we have discovered high quality connections between the CRC disease state and the candidate compounds, and that the gene signature we created may be used as a potential therapeutic target in treating the disease. The method we proposed is highly effective in generating quality gene signature through multiple datasets; the publication of the combined CRC gene signature and the list of candidate compounds from this work will benefit both cancer and systems biology research communities for further development and investigations. PMID:26356760

  6. Biology of colorectal cancer

    PubMed Central

    Arvelo, Francisco; Sojo, Felipe; Cotte, Carlos

    2015-01-01

    Colorectal cancer is a serious health problem, a challenge for research, and a model for studying the molecular mechanisms involved in its development. According to its incidence, this pathology manifests itself in three forms: family, hereditary, and most commonly sporadic, apparently not associated with any hereditary or familial factor. For the types having inheritance patterns and a family predisposition, the tumours develop through defined stages ranging from adenomatous lesions to the manifestation of a malignant tumour. It has been established that environmental and hereditary factors contribute to the development of colorectal cancer, as indicated by the accumulation of mutations in oncogenes, genes which suppress and repair DNA, signaling the existence of various pathways through which the appearance of tumours may occur. In the case of the suppressive and mutating tracks, these are characterised by genetic disorders related to the phenotypical changes of the morphological progression sequence in the adenoma/carcinoma. Moreover, alternate pathways through mutation in BRAF and KRAS genes are associated with the progression of polyps to cancer. This review surveys the research done at the cellular and molecular level aimed at finding specific alternative therapeutic targets for fighting colorectal cancer. PMID:25932044

  7. Chemoprevention of colorectal cancer

    PubMed Central

    LANGMAN, M; BOYLE, P

    1998-01-01

    Department of Medicine, Queen Elizabeth Hospital, Birmingham B15 2TH, UK P BOYLE Colorectal cancer is the fourth commonest form of cancer in men with 678 000 estimated new cases per year worldwide, representing 8.9% of all new cancers. The disease is most frequent in Occidental countries and particularly so in North America, Australia, New Zealand, and parts of Europe. Prospects for colorectal cancer control are bright and a number of possible approaches could prove fruitful. Among these, pharmaceutical measures seem to be valid and logical approaches to the prevention of colorectal cancer and diminishing its impact. Such approaches could concentrate in primary prevention in at-risk subjects or be applied in altering the course of precursor or established disease. Treatments used must fulfil basic requirements of biological plausibility and safety in continued use in large numbers of subjects. Those available include vitamins and minerals, and other drugs with potential as antioxidants, immune modulators or promoters of cell differentiation or apoptosis. Of the various regimens suggested, vitamin A supplementation may even predispose to adverse outcomes, and antioxidant vitamins in general have no coherent body of evidence to support their use. N-acetylcysteine and ursodeoxycholic acid have promising characteristics but there are as yet no clinical data to support the use of the former in gut epithelial cancer, and formal dose ranging studies must be carried out before the latter is submitted to large scale trial. Folate shows promising characteristics but non-steroidal anti-inflammatory drugs and vitamin D seem the most promising agents. Both seem to reduce the incidence of disease, and to reduce growth rates and/or induce differentiation or apoptosis in gut epithelial cancer cells. Both are also well understood pharmacologically. They may be preferred to newer selective compounds in the same class until these newer compounds are confirmed as safe for widespread

  8. Immunotherapy for colorectal cancer.

    PubMed

    Koido, Shigeo; Ohkusa, Toshifumi; Homma, Sadamu; Namiki, Yoshihisa; Takakura, Kazuki; Saito, Keisuke; Ito, Zensho; Kobayashi, Hiroko; Kajihara, Mikio; Uchiyama, Kan; Arihiro, Seiji; Arakawa, Hiroshi; Okamoto, Masato; Gong, Jianlin; Tajiri, Hisao

    2013-12-14

    The incidence of colorectal cancer (CRC) is on the rise, and the prognosis for patients with recurrent or metastatic disease is extremely poor. Although chemotherapy and radiation therapy can improve survival rates, it is imperative to integrate alternative strategies such as immunotherapy to improve outcomes for patients with advanced CRC. In this review, we will discuss the effect of immunotherapy for inducing cytotoxic T lymphocytes and the major immunotherapeutic approaches for CRC that are currently in clinical trials, including peptide vaccines, dendritic cell-based cancer vaccines, whole tumor cell vaccines, viral vector-based cancer vaccines, adoptive cell transfer therapy, antibody-based cancer immunotherapy, and cytokine therapy. The possibility of combination therapies will also be discussed along with the challenges presented by tumor escape mechanisms. PMID:24379570

  9. [Genetics of colorectal cancer].

    PubMed

    Balaguer, Francesc

    2012-09-01

    Colorectal cancer (CRC) is one of the most frequent neoplasms in developed countries and up to 5% of all cases occur in the context of a hereditary syndrome. These hereditary forms often require a high index of suspicion for their diagnosis and specific and specialized management. Moreover, a diagnosis of hereditary CRC has major consequences not only for the patient--for whom there are highly effective preventive measures--but also for the patient's relatives, who may carry the same condition. The most significant advances in the field of hereditary CRC have been produced in the diagnosis and characterization of Lynch's syndrome and serrated polyposis syndrome.

  10. [Genetics of colorectal cancer].

    PubMed

    Balaguer, Francesc

    2013-10-01

    Up to 5% of all cases of colorectal cancer (CRC) are due to a known hereditary syndrome. These hereditary forms often require a high degree of suspicion for their diagnosis and specific and specialized management. Moreover, a diagnosis of hereditary CRC has important consequences, not only for patients-for whom highly effective preventive measures are available-, but also for their relatives, who may be carriers of the same condition. The most significant advances in the field of hereditary CRC have been produced in the diagnosis and characterization of these syndromes and in the discovery of new causative genes.

  11. Conversion Therapy Using mFOLFOX6 With Panitumumab for Unresectable Liver Metastases From Multiple Colorectal Cancers With Familial Adenomatous Polyposis

    PubMed Central

    Toiyama, Yuji; Inoue, Yasuhiro; Kitajima, Takahito; Okigami, Masato; Kawamura, Mikio; Kawamoto, Aya; Okugawa, Yoshinaga; Hiro, Jyunichiro; Tanaka, Koji; Mohri, Yasuhiko; Kusunoki, Masato

    2014-01-01

    A 39-year-old man received a diagnosis of unresectable multiple liver metastases from multiple colorectal cancers with familial adenomatous polyposis. After construction of an ileostomy, modified FOLFOX6 (mFOLFOX6) with panitumumab was administrated because rectal cancer and sigmoid colon cancer are KRAS wild type. The 13 courses of chemotherapy resulted in a marked reduction in the size of liver metastases and sigmoid colon cancer. Consequently, curative resection with total colectomy, ileal pouch anal anastomosis, and liver metastasis resection with radiofrequency ablation was performed. Progression of KRAS wild-type rectal cancer after chemotherapy suggested that each clone from rectal and sigmoid colon cancer might have a different sensitivity to epidermal growth factor receptor antibody. Immunohistochemical analysis revealed loss of PTEN expression in rectal cancer compared with liver metastases from sigmoid colon cancer, showing that the difference of mFOLFOX6 with panitumumab might be related to activation of the PI3K-AKT pathway. PMID:25437589

  12. Primary Prevention of Colorectal Cancer

    PubMed Central

    Chan, Andrew T.; Giovannucci, Edward L.

    2010-01-01

    Colorectal cancer has been strongly associated with a Western lifestyle. In the past several decades, much has been learned about the dietary, lifestyle, and medication risk factors for this malignancy. Although there is controversy about the role of specific nutritional factors, consideration of the dietary pattern as a whole appears useful for formulating recommendations. For example, several studies have shown that high intake of red and processed meats, highly refined grains and starches, and sugars is related to increased risk of colorectal cancer. Replacing these factors with poultry, fish, and plant sources as the primary source of protein; unsaturated fats as the primary source of fat; and unrefined grains, legumes and fruits as the primary source of carbohydrates is likely to lower risk of colorectal cancer. Although a role for supplements, including vitamin D, folate, and vitamin B6, remains uncertain, calcium supplementation is likely to be at least modestly beneficial. With respect to lifestyle, compelling evidence indicates that avoidance of smoking and heavy alcohol use, prevention of weight gain, and the maintenance of a reasonable level of physical activity are associated with markedly lower risks of colorectal cancer. Medications such as aspirin and non-steroidal anti-inflammatory drugs and post-menopausal hormones for women are associated with significant reductions in colorectal cancer risk, though their utility is affected by associated risks. Taken together, modifications in diet and lifestyle should substantially reduce the risk of colorectal cancer and could complement screening in reducing colorectal cancer incidence. PMID:20420944

  13. Colorectal cancer in Portugal.

    PubMed

    Pinto, Carlos Gouveia; Paquete, Ana Teresa; Pissarra, Irene

    2010-01-01

    Increasing diagnosis and deaths caused by colorectal cancer (CRC) warrant closer examination of affected patients and focus on management of CRC in Portugal. In order to assess the extent and quality of the information available in Portugal, we first analyse Portuguese cancer registries and then the management of CRC by discussing the diagnostic process and medical care provided, especially pharmaceuticals. Other cancer indications are mentioned in order to illustrate current approaches of cancer in Portugal. Current national data on cancer patients are scarce and there are divergencies in methods of data collection and treatment amongst regional cancer registries. However, the available data is sufficient enough to understand the dimension of CRC, with age-standardised incidence of 37 per 100,000 and mortality of 31 per 100,000 annually. An ongoing project is restructuring health services to improve efficiency and quality, however, some problems exist. The regional inequity of access to health care facilities and long waiting times for diagnostic examinations and surgery are major examples. Despite the non-availability of clinical guidelines, a pilot screening programme started at the beginning of 2009 in the Centre Region of the country. It is hoped that this overview will provide the basis for discussion on improvements in CRC management in Portugal and lead to better outcomes.

  14. Vaccination of metastatic colorectal cancer patients with matured dendritic cells loaded with multiple major histocompatibility complex class I peptides.

    PubMed

    Kavanagh, Brian; Ko, Andrew; Venook, Alan; Margolin, Kim; Zeh, Herbert; Lotze, Michael; Schillinger, Brian; Liu, Weihong; Lu, Ying; Mitsky, Peggie; Schilling, Marta; Bercovici, Nadege; Loudovaris, Maureen; Guillermo, Roy; Lee, Sun Min; Bender, James; Mills, Bonnie; Fong, Lawrence

    2007-10-01

    Developing a process to generate dendritic cells (DCs) applicable for multicenter trials would facilitate cancer vaccine development. Moreover, targeting multiple antigens with such a vaccine strategy could enhance the efficacy of such a treatment approach. We performed a phase 1/2 clinical trial administering a DC-based vaccine targeting multiple tumor-associated antigens to patients with advanced colorectal cancer (CRC). A qualified manufacturing process was used to generate DC from blood monocytes using granulocyte macrophage colony-stimulating factor and IL-13, and matured for 6 hours with Klebsiella-derived cell wall fraction and interferon-gamma (IFN-gamma). DCs were also loaded with 6 HLA-A*0201 binding peptides derived from carcinoembryonic antigen (CEA), MAGE, and HER2/neu, as well as keyhole limpet hemocyanin protein and pan-DR epitope peptide. Four planned doses of 35x10(6) cells were administered intradermally every 3 weeks. Immune response was assessed by IFN-gamma enzyme-linked immunosorbent spot (ELISPOT). Matured DC possessed an activated phenotype and could prime T cells in vitro. In the trial, 21 HLA-A2+ patients were apheresed, 13 were treated with the vaccine, and 11 patients were evaluable. No significant treatment-related toxicity was reported. T-cell responses to a CEA-derived peptide were detected by ELISPOT in 3 patients. T cells induced to CEA possessed high avidity T-cell receptors. ELISPOT after in vitro restimulation detected responses to multiple peptides in 2 patients. All patients showed progressive disease. This pilot study in advanced CRC patients demonstrates DC-generated granulocyte macrophage colony-stimulating factor and IL-13 matured with Klebsiella-derived cell wall fraction and IFN-gamma can induce immune responses to multiple tumor-associated antigens in patients with advanced CRC.

  15. [Hereditary and familial colorectal cancer].

    PubMed

    Balaguer, Francesc

    2014-09-01

    Up to 5% of all colorectal cancer cases are caused by a known hereditary syndrome. These hereditary types often need a higher degree of clinical suspicion to be diagnosed and require specific and specialized management. In addition, diagnosing hereditary colorectal cancer has significant consequences not only for the patient, for whom there are effective preventative measures, but also for their families, who could be carriers of the condition. The most significant advances in the field of colorectal cancer have come from the diagnosis and characterization of these syndromes.

  16. Population screening for colorectal cancer.

    PubMed

    2006-09-01

    Each year in the UK, around 16,000 people die from colorectal cancer. At disease presentation, around 55% of people have advanced cancer that has spread to lymph nodes, metastasised to other organs or is so locally advanced that surgery is unlikely to be curative (Dukes' stage C or D). Overall 5-year survival for colorectal cancer in the UK is around 47-51% (compared to 64% in the USA), but only 7% at most in those presenting with metastatic disease. These facts underlie the current introduction of national bowel screening programmes in the UK. Here we assess the role of screening of the general population in reducing mortality from colorectal cancer. We do not consider the screening arrangements needed for high-risk populations, including those with inflammatory bowel disease or a strong family history of colorectal cancer. PMID:17009566

  17. Regulatory T cells with multiple suppressive and potentially pro-tumor activities accumulate in human colorectal cancer.

    PubMed

    Timperi, Eleonora; Pacella, Ilenia; Schinzari, Valeria; Focaccetti, Chiara; Sacco, Luca; Farelli, Francesco; Caronna, Roberto; Del Bene, Gabriella; Longo, Flavia; Ciardi, Antonio; Morelli, Sergio; Vestri, Anna Rita; Chirletti, Piero; Barnaba, Vincenzo; Piconese, Silvia

    2016-07-01

    Tregs can contribute to tumor progression by suppressing antitumor immunity. Exceptionally, in human colorectal cancer (CRC), Tregs are thought to exert beneficial roles in controlling pro-tumor chronic inflammation. The goal of our study was to characterize CRC-infiltrating Tregs at multiple levels, by phenotypical, molecular and functional evaluation of Tregs from the tumor site, compared to non-tumoral mucosa and peripheral blood of CRC patients. The frequency of Tregs was higher in mucosa than in blood, and further significantly increased in tumor. Ex vivo, those Tregs suppressed the proliferation of tumor-infiltrating CD8(+) and CD4(+) T cells. A differential compartmentalization was detected between Helios(high) and Helios(low) Treg subsets (thymus-derived versus peripherally induced): while Helios(low) Tregs were enriched in both sites, only Helios(high) Tregs accumulated significantly and specifically in tumors, displayed a highly demethylated TSDR region and contained high proportions of cells expressing CD39 and OX40, markers of activation and suppression. Besides the suppression of T cells, Tregs may contribute to CRC progression also through releasing IL-17, or differentiating into Tfr cells that potentially antagonize a protective Tfh response, events that were both detected in tumor-associated Tregs. Overall, our data indicate that Treg accumulation may contribute through multiple mechanisms to CRC establishment and progression. PMID:27622025

  18. Progression of colorectal cancer is associated with multiple tumor suppressor gene defects but inhibition of tumorigenicity is accomplished by correction of any single defect via chromosome transfer

    SciTech Connect

    Goyette, M.C.; Fasching, C.L.; Stanbridge, E.J. ); Cho, K.; Levy, D.B.; Kinzler, K.W.; Vogelstein, B. ); Paraskeva, C. )

    1992-03-01

    Colorectal cancer has been associated with the activation of ras oncogenes and with the deletion of multiple chromosomal regions including chromosomes 5q, 17p, and 18q. The candidate tumor suppressor genes from these regions are, respectively, MCC and/or APC, p53, and DCC. In order to further understanding of the molecular and genetic mechanisms involved in tumor progression and, thereby, of normal cell growth, it is important to determine whether defects in one or more of these loci contribute functionally in the progression to malignancy in colorectal cancer and whether correction of any of these defects restores normal growth control in vitro and in vivo. To address this question, the authors have utilized the technique of microcell-mediated chromosome transfer to introduce normal human chromosomes 5, 17, and 18 individually into recipient colorectal cancer cells. Additionally, chromosome 15 was introduced into SW480 cells as an irrelevant control chromosome. While the introduction of chromosome 17 into the tumorigenic colorectal cell line SW480 yielded no viable clones, cell lines were established after the introduction of chromosomes 15, 5, and 18. SW480-chromosome 5 hybrids are strongly suppressed for tumorigenicity, while SW480-chromosome 18 hybrids produce slowly growing tumors in some of the animals injected. Hybrids containing the introduced chromosome 5 express the APC gene present on that chromosome as well as the endogenous mutant transcript. Expression of the putative tumor suppressor gene, DCC, was seen in the clones containing the introduced chromosome 18 but was significantly reduced in several of the tumor reconstitute cell lines. Our findings indicate that while multiple defects in tumor suppressor genes seem to be required for progression to the malignant state in colorectal cancer, correction of only a single defect can have significant effects in vivo and/or in vitro.

  19. Colorectal cancer screening: The role of the noninvasive options.

    PubMed

    Dickerson, Lisa; Varcak, Susan Combs

    2016-09-01

    Recommended screening options for colorectal cancer are divided into noninvasive stool-based options, and invasive procedure-based options. Because multiple screening strategies are effective, efforts to reduce deaths from colorectal cancer should focus on maximizing the number of patients who are screened. This article reviews noninvasive stool-based screening options. PMID:27575898

  20. Animal Models of Colorectal Cancer

    PubMed Central

    Johnson, Robert L.; Fleet, James C.

    2012-01-01

    Colorectal cancer is a heterogeneous disease that afflicts a large number of people in the United States. The use of animal models has the potential to increase our understanding of carcinogenesis, tumor biology, and the impact of specific molecular events on colon biology. In addition, animal models with features of specific human colorectal cancers can be used to test strategies for cancer prevention and treatment. In this review we provide an overview of the mechanisms driving human cancer, we discuss the approaches one can take to model colon cancer in animals, and we describe a number of specific animal models that have been developed for the study of colon cancer. We believe that there are many valuable animal models to study various aspects of human colorectal cancer. However, opportunities for improving upon these models exist. PMID:23076650

  1. Animal models of colorectal cancer.

    PubMed

    Johnson, Robert L; Fleet, James C

    2013-06-01

    Colorectal cancer is a heterogeneous disease that afflicts a large number of people in the USA. The use of animal models has the potential to increase our understanding of carcinogenesis, tumor biology, and the impact of specific molecular events on colon biology. In addition, animal models with features of specific human colorectal cancers can be used to test strategies for cancer prevention and treatment. In this review, we provide an overview of the mechanisms driving human cancer, we discuss the approaches one can take to model colon cancer in animals, and we describe a number of specific animal models that have been developed for the study of colon cancer. We believe that there are many valuable animal models to study various aspects of human colorectal cancer. However, opportunities for improving upon these models exist.

  2. Impact of multiple Alcohol Dehydrogenase gene polymorphisms on risk of laryngeal, esophageal, gastric and colorectal cancers in Chinese Han population

    PubMed Central

    An, Jiaze; Zhao, Junsheng; Zhang, Xiyang; Ding, Rui; Geng, Tingting; Feng, Tian; Jin, Tianbo

    2015-01-01

    Alcohol intake is positively associated with the risk of upper aerodigestive tract (UADT) cancers; but its effect on gastric or colorectal cancer is controversial. Previous study had identified several single nucleotide polymorphisms (SNPs) of Alcohol Dehydrogenase (ADH) genes associated with UADT cancers in European and Japanese populations. We sought to determine if these SNPs associated with laryngeal, esophageal, gastric or colorectal cancer in Chinese population. We conducted a case-control study among 1577 cases and 1013 healthy controls from northwest China. Five SNPs associated with UADT cancers risk were selected from previous genome-wide association studies and genotyped using Sequenom Mass-ARRAY technology. Odds ratios and 95% confidence intervals (CIs) were calculated by unconditional logistic regression adjusting for age and gender. We identified that the minor alleles of rs1789924 and rs971074 were associated with decreased risk of laryngeal cancer (OR = 0.311; 95% CI = 0.161-0.602; P < 0.001) and esophagus cancer (OR = 0.711; 95% CI = 0.526-0.962; P = 0.027) in allelic model analysis, respectively. In the genetic model analysis, we found the “C/T” genotype of rs1789924 was associated with decreased laryngeal cancer risk in codominant model (P = 0.046) and overdominant model (P = 0.013); the “C/T-T/T” genotype of rs1789924 was associated with reduced risk of laryngeal cancer under dominant model (P = 0.013). Additionally, none of the SNPs was associated with gastric or colorectal cancer in our study. Our data shed new light on the association between ADH SNPs and respiratory and digestive tract cancers susceptibility in the Han Chinese population. PMID:26396927

  3. Survivorship Care Plan in Promoting Physical Activity in Breast or Colorectal Cancer Survivors in Wisconsin

    ClinicalTrials.gov

    2016-08-19

    Cancer Survivor; Healthy Subject; Stage I Colorectal Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIA Colorectal Cancer; Stage IIB Breast Cancer; Stage IIB Colorectal Cancer; Stage IIC Colorectal Cancer; Stage IIIA Breast Cancer; Stage IIIA Colorectal Cancer; Stage IIIB Breast Cancer; Stage IIIB Colorectal Cancer; Stage IIIC Breast Cancer; Stage IIIC Colorectal Cancer

  4. Colorectal Cancer Risk Prediction Models

    Cancer.gov

    Developing statistical models that estimate the probability of developing colorectal cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  5. Immunotherapy of Colorectal Cancer.

    PubMed

    Jäger, Dirk; Halama, Niels; Zörnig, Inka; Klug, Paula; Krauss, Jürgen; Haag, Georg-Martin

    2016-01-01

    It is known that the immune response, reflected by high T cell infiltrates in primary tumors and metastases, influences the clinical course of colorectal cancer (CRC). Therefore, immunotherapy concepts have been adapted from other tumor entities, which typically rely on the activation of T cells in the tumor microenvironment (e.g. blockade of the immune checkpoint molecules PD-1 and CTLA-4). However, most of the strategies using the approved checkpoint inhibitors and/or combination strategies have more or less failed to produce impressive results in early phase trials in CRC. Therefore, a number of novel targets for checkpoint inhibition are currently in early phase clinical testing (TIM-3, Lag-3, OX40, GITR, 4-1BB, CD40, CD70). A simple activation of infiltrating T cells will not, however, lead to a meaningful anti-tumor response without modulating the environmental factors in CRC. Thus, it is absolutely necessary to improve our understanding of the complex regulation of the tumor microenvironment in CRC to design individual combination treatments leading to effective immune control. PMID:27259331

  6. Colorectal cancers and chlorinated water

    PubMed Central

    El-Tawil, Ahmed Mahmoud

    2016-01-01

    Published reports have revealed increased risk of colorectal cancers in people exposed to chlorinated drinking water or chemical derivatives of chlorination. Oestrogen plays a dual positive functions for diminishing the possibilities of such risk by reducing the entrance, and increasing the excretion, of these chemicals. In addition, there are supplementary measures that could be employed in order to reduce this risk further, such as boiling the drinking water, revising the standard concentrations of calcium, magnesium and iron in the public drinking water and prescribing oestrogen in susceptible individuals. Hypo-methylation of genomic DNA could be used as a biological marker for screening for the potential development of colorectal cancers. PMID:27096035

  7. Colorectal Cancer Coalition

    MedlinePlus

    ... Reports Press Room Contact Us Sign Up We fight for Moms Dads Uncles Aunts Friends Brothers Sisters ... on Congress. Take Action Your Guide in the Fight Free resource for stage III & stage IV colorectal ...

  8. Epigenetics and Colorectal Cancer Pathogenesis

    PubMed Central

    Bardhan, Kankana; Liu, Kebin

    2013-01-01

    Colorectal cancer (CRC) develops through a multistage process that results from the progressive accumulation of genetic mutations, and frequently as a result of mutations in the Wnt signaling pathway. However, it has become evident over the past two decades that epigenetic alterations of the chromatin, particularly the chromatin components in the promoter regions of tumor suppressors and oncogenes, play key roles in CRC pathogenesis. Epigenetic regulation is organized at multiple levels, involving primarily DNA methylation and selective histone modifications in cancer cells. Assessment of the CRC epigenome has revealed that virtually all CRCs have aberrantly methylated genes and that the average CRC methylome has thousands of abnormally methylated genes. Although relatively less is known about the patterns of specific histone modifications in CRC, selective histone modifications and resultant chromatin conformation have been shown to act, in concert with DNA methylation, to regulate gene expression to mediate CRC pathogenesis. Moreover, it is now clear that not only DNA methylation but also histone modifications are reversible processes. The increased understanding of epigenetic regulation of gene expression in the context of CRC pathogenesis has led to development of epigenetic biomarkers for CRC diagnosis and epigenetic drugs for CRC therapy. PMID:24216997

  9. Hereditary Colorectal Cancer: Genetics and Screening.

    PubMed

    Brosens, Lodewijk A A; Offerhaus, G Johan A; Giardiello, Francis M

    2015-10-01

    Colorectal cancer (CRC) is the third most common cancer and the third leading cause of cancer death in men and women in the United States. About 30% of patients with CRC report a family history of CRC. However, only 5% of CRCs arise in the setting of a well-established mendelian inherited disorder. In addition, serrated polyposis is a clinically defined syndrome with multiple serrated polyps in the colorectum and an increased CRC risk for which the genetics are unknown. This article focuses on genetic and clinical aspects of Lynch syndrome, familial adenomatous polyposis, and MUTYH-associated polyposis.

  10. General aspects of colorectal cancer.

    PubMed

    Centelles, Josep J

    2012-01-01

    Colorectal cancer (CRC) is one of the main causes of death. Cancer is initiated by several DNA damages, affecting proto-oncogenes, tumour suppressor genes, and DNA repairing genes. The molecular origins of CRC are chromosome instability (CIN), microsatellite instability (MSI), and CpG island methylator phenotype (CIMP). A brief description of types of CRC cancer is presented, including sporadic CRC, hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndromes, familiar adenomatous polyposis (FAP), MYH-associated polyposis (MAP), Peutz-Jeghers syndrome (PJS), and juvenile polyposis syndrome (JPS). Some signalling systems for CRC are also described, including Wnt-β-catenin pathway, tyrosine kinase receptors pathway, TGF-β pathway, and Hedgehog pathway. Finally, this paper describes also some CRC treatments.

  11. Stem cells, colorectal cancer and cancer stem cell markers correlations.

    PubMed

    Cherciu, Irina; Bărbălan, A; Pirici, D; Mărgăritescu, C; Săftoiu, A

    2014-01-01

    : The idea of stem cells as being progenitors of cancer was initially controversial, but later supported by research in the field of leukemia and solid tumors. Afterwards, it was established that genetic abnormalities can affect the stem and progenitor cells, leading to uncontrolled replication and deregulated differentiation. These alterations will cause the changeover to cancerous stem cells (CSC) having two main characteristics: tumor initiation and maintenance. This review will focus on the colorectal cancer stem cell (CR-CSCs) theory which provides a better understanding of different tumor processes: initiation, aggressive growth, recurrence, treatment resistance and metastasis. A search in PubMed/Medline was performed using the following keywords: colorectal cancer stem cells (CR-CSCs), colorectal neoplasms stem cells, colorectal cancer stem cell (CR-CSCs) markers, etc. Electronic searches were supplemented by hand searching reference lists, abstracts and proceedings from meetings. Isolation of CR-CSCs can be achieved by targeting and selecting subpopulation of tumor cells based on expression of one or multiple cell surface markers associated with cancer self-renewal, markers as: CD133, CD166, CD44, CD24, beta1 integrin-CD29, Lgr5, EpCAM (ESA), ALDH-1, Msi-1, DCAMLK1 or EphB receptors. The identification and localization of CR-CSCs through different markers will hopefully lead to a better stratification of prognosis and treatment response, as well as the development of new effective strategies for cancer management.

  12. Systemic Treatment of Colorectal Cancer

    PubMed Central

    Wolpin, Brian M.; Mayer, Robert J.

    2008-01-01

    Colorectal cancer is the fourth most common non-cutaneous malignancy in the United States and the second most frequent cause of cancer-related death. Over the past 12 years, significant progress has been made in the systemic treatment of this malignant condition. Six new chemotherapeutic agents have been introduced, increasing median overall survival for patients with metastatic colorectal cancer from less than 9 months with no treatment to approximately 24 months. For patients with stage III (lymph node positive) colon cancer, an overall survival benefit for fluorouracil-based chemotherapy has been firmly established, and recent data have shown further efficacy for the inclusion of oxaliplatin in such adjuvant treatment programs. For patients with stage II colon cancer, the use of adjuvant chemotherapy remains controversial, but may be appropriate in a subset of individuals at higher risk for disease recurrence. Ongoing randomized clinical trials are evaluating how best to combine currently available therapies, while smaller studies are evaluating new agents, with the goal of continued progress in prolonging life among patients with metastatic colorectal cancer and increasing cure rates among those with resectable disease. PMID:18471507

  13. What's New in Colorectal Cancer Research and Treatment?

    MedlinePlus

    ... Next Topic Additional resources for colorectal cancer What’s new in colorectal cancer research? Research is always going ... ways to find colorectal cancer early by studying new types of screening tests and improving the ones ...

  14. Percentage of Adults Who Receive Colorectal Cancer Screening as Appropriate

    MedlinePlus

    ... Appropriate Percentage of Adults Who Receive Colorectal Cancer Screening as Appropriate Colorectal cancer is the second leading ... Percentage of Adults Who Receive Recommended Colorectal Cancer Screening by Age Group 78pm-ubty Download these data » ...

  15. The diagnostics of colorectal cancer.

    PubMed

    Swiderska, Magdalena; Choromańska, Barbara; Dąbrowska, Ewelina; Konarzewska-Duchnowska, Emilia; Choromańska, Katarzyna; Szczurko, Grzegorz; Myśliwiec, Piotr; Dadan, Jacek; Ladny, Jerzy Robert; Zwierz, Krzysztof

    2014-01-01

    Colorectal cancer (CRC) is one of the most frequent human malignant neoplasms. CRC has an estimated incidence of more than 1,000,000 new cases annually worldwide. Approximately one out of three people who develop CRC dies from the disease. Furthermore, CRC often affects inhabitants of industrialized countries in comparison to less developed countries. Several markers of colon cancer, including CEA, CA-19-9, TPS, TAG-72 and lysosomal hydrolases, have been identified and are now being adopted in routine clinical practice. Increased values of these markers are often the first signal of recurrence or metastases, which is useful in prediction and prognosis of clinical outcome of patients with CRC. Determination of the activity of lysosomal exoglycosidases in body fluids may bring some hope of improving diagnosis of colorectal cancer. However, it has to be remembered that currently the most effective diagnostic method of CRC is endoscopy. PMID:24876814

  16. Inflammatory networks underlying colorectal cancer.

    PubMed

    Lasry, Audrey; Zinger, Adar; Ben-Neriah, Yinon

    2016-03-01

    Inflammation is emerging as one of the hallmarks of cancer, yet its role in most tumors remains unclear. Whereas a minority of solid tumors are associated with overt inflammation, long-term treatment with non-steroidal anti-inflammatory drugs is remarkably effective in reducing cancer rate and death. This indicates that inflammation might have many as-yet-unrecognized facets, among which an indolent course might be far more prevalent than previously appreciated. In this Review, we explore the various inflammatory processes underlying the development and progression of colorectal cancer and discuss anti-inflammatory means for its prevention and treatment.

  17. Current concepts in colorectal cancer prevention

    PubMed Central

    Thompson, Patricia A; Gerner, Eugene W

    2009-01-01

    Colorectal cancer chemoprevention, or chemoprophylaxis, is a drug-based approach to prevent colorectal cancer. Preventing colorectal adenomas with currently available agents demonstrates the promise of pharmacologic strategies directed at critical regulatory pathways. However, agent toxicity, lesion breakthrough and competing efficacy from endoscopy procedures challenge population-based implementation. This article reviews the role of colorectal cancer chemoprevention in the context of existing screening and surveillance guidelines and practice. Emphasis is placed on the role of the colorectal adenoma as a cancer precursor and its surrogacy in assessing individual risk and for evaluating chemoprevention efficacy. We discuss the importance of risk stratification for identifying subjects at moderate-to-high risk for colorectal cancer who are most likely to benefit from chemoprevention at an acceptable level of risk. PMID:19673624

  18. Colorectal cancer in Jordan: prevention and care.

    PubMed

    Ahmad, Muayyad M; Dardas, Latefa; Dardas, Lubna; Ahmad, Huthaifa

    2015-12-01

    The aim of this study was to describe the knowledge, attitudes, and practices toward colorectal cancer prevention and care in Jordan. A survey was designed to produce reliable estimates for the population's knowledge, attitudes, and practices in all 12 governorates of Jordan by using stratified random sampling. A representative sample of the adult population in Jordan completed a comprehensive tool which explored participants' knowledge about the risk factors associated with colorectal cancer, cancer prevention through lifestyle changes, and early cancer diagnosis and screening. According to the participants (n = 3196), colorectal cancer had the second highest percentage of screening recommendation (12.6%) after breast cancer (57.3%). Only 340 individuals (11%) reported ever screening for cancer. About 20% of the participants had heard of one of the screening tests for colorectal cancer. In fact, only 290 (9.1%) participants had performed the colorectal cancer screening tests. This study provides data that will help colorectal cancer prevention and treatment programs and may enhance the efficiency of colorectal cancer-controlling programs. The findings confirm the necessity of starting colorectal screening intervention that targets the most vulnerable individuals.

  19. Improving colorectal cancer screening: fact and fantasy

    NASA Astrophysics Data System (ADS)

    Van Dam, Jacques

    2008-02-01

    Premalignant diseases of the gastrointestinal tract, such as Barrett's esophagus, long-standing ulcerative colitis, and adenomatous polyps, have a significantly increased risk for development of adenocarcinoma, most often through an intermediate stage of dysplasia. Adenocarcinoma of the colon is the second most common cancer in the United States. Because patients with colorectal cancer often present with advanced disease, the outcomes are associated with significant morbidity and mortality. Effective methods of early detection are essential. As non-polypoid dysplasia is not visible using conventional endoscopy, surveillance of patients with Barrett's esophagus and ulcerative colitis is performed via a system in which multiple random biopsies are obtained at prescribed intervals. Sampling error and missed diagnoses occur frequently and render current screening methods inadequate. Also, the examination of a tissue biopsy is time consuming and costly, and significant intra- and inter-observer variation may occur. The newer methods discussed herein demonstrate the potential to solve these problems by early detection of disease with high sensitivity and specificity. Conventional endoscopy is based on the observation of white light reflected off the tissue surface. Subtle changes in color and shadow reveal structural changes. New developments in optical imaging go beyond white light, exploiting other properties of light. Several promising methods will be discussed at this meeting and shall be briefly discussed below. However, few such imaging modalities have arrived at our clinical practice. Some much more practical methods to improve colorectal cancer screening are currently being evaluated for their clinical impact. These methods seek to overcome limitations other than those of detecting dysplasia not visible under white light endoscopy. The current standard practice of colorectal cancer screening utilizes colonoscopy, an uncomfortable, sometimes difficult medical

  20. Red Meat and Colorectal Cancer

    PubMed Central

    2015-01-01

    Colorectal cancer (CRC) is the third most common cancer in men and the second in women worldwide. More than half of cases occur in more developed countries. The consumption of red meat (beef, pork, lamb, veal, mutton) is high in developed countries and accumulated evidence until today demonstrated a convincing association between the intake of red meat and especially processed meat and CRC risk. In this review, meta-analyses of prospective epidemiological studies addressed to this association, observed link of some subtypes of red meat with CRC risk, potential carcinogenic compounds, their mechanisms and actual recommendations of international guidelines are presented. PMID:26779313

  1. Molecular Diagnostic Applications in Colorectal Cancer

    PubMed Central

    Huth, Laura; Jäkel, Jörg; Dahl, Edgar

    2014-01-01

    Colorectal cancer, a clinically diverse disease, is a leading cause of cancer-related death worldwide. Application of novel molecular diagnostic tests, which are summarized in this article, may lead to an improved survival of colorectal cancer patients. Distinction of these applications is based on the different molecular principles found in colorectal cancer (CRC). Strategies for molecular analysis of single genes (as KRAS or TP53) as well as microarray based techniques are discussed. Moreover, in addition to the fecal occult blood testing (FOBT) and colonoscopy some novel assays offer approaches for early detection of colorectal cancer like the multitarget stool DNA test or the blood-based Septin 9 DNA methylation test. Liquid biopsy analysis may also exhibit great diagnostic potential in CRC for monitoring developing resistance to treatment. These new diagnostic tools and the definition of molecular biomarkers in CRC will improve early detection and targeted therapy of colorectal cancer.

  2. Tailored Telephone Counseling Increases Colorectal Cancer Screening

    ERIC Educational Resources Information Center

    Rawl, Susan M.; Christy, Shannon M.; Monahan, Patrick O.; Ding, Yan; Krier, Connie; Champion, Victoria L.; Rex, Douglas

    2015-01-01

    To compare the efficacy of two interventions to promote colorectal cancer screening participation and forward stage movement of colorectal cancer screening adoption among first-degree relatives of individuals diagnosed with adenomatous polyps. One hundred fifty-eight first-degree relatives of individuals diagnosed with adenomatous polyps were…

  3. Evolving management of colorectal cancer

    PubMed Central

    van Zijp, Jochem van der Voort; Hoekstra, Harald J; Basson, Marc D

    2008-01-01

    This article reviews recent advances in surgical techniques and adjuvant therapies for colorectal cancer, including total mesorectal excision, the resection of liver and lung metastasis and advances in chemoradiation and foreshadows some interventions that may lie just beyond the frontier. In particular, little is known about the intracellular and extracellular cascades that may influence colorectal cancer cell adhesion and metastasis. Although the phosphorylation of focal adhesion kinases and focal adhesion associated proteins in response to integrin-mediated cell matrix binding (”outside in integrin signaling”) is well described, the stimulation of cell adhesion by intracellular signals activated by pressure prior to adhesion represents a different signal paradigm. However, several studies have suggested that increased pressure and shear stress activate cancer cell adhesion. Further studies of the pathways that regulate integrin-driven cancer cell adhesion may identify ways to disrupt these signals or block integrin-mediated adhesion so that adhesion and eventual metastasis can be prevented in the future. PMID:18609678

  4. Management of Colorectal Cancer in Older Adults.

    PubMed

    Hubbard, Joleen M

    2016-02-01

    Treatment for colorectal cancer should not be based on age alone. Pooled analyses from clinical trials show that fit older adults are able to tolerate treatment well with similar efficacy as younger adults. When an older adult is considered for treatment, the clinical encounter must evaluate for deficits in physical and cognitive function, and assess comorbidities, medications, and the degree of social support, all which have may affect tolerance of treatment. Based on the degree of fitness of the patient, multiple alternatives to aggressive treatment regimens and strategies exist to minimize toxicity and preserve quality of life during treatment.

  5. New registry: National Cancer Patient Registry--Colorectal Cancer.

    PubMed

    Wendy, L; Radzi, M

    2008-09-01

    Colorectal cancer is emerging as one of the commonest cancers in Malaysia. Data on colorectal cancer from the National Cancer Registry is very limited. Comprehensive information on all aspects of colorectal cancer, including demographic details, pathology and treatment outcome are needed as the management of colorectal cancer has evolved rapidly over the years involving several disciplines including gastroenterology, surgery, radiology, pathology and oncology. This registry will be an important source of information that can help the development of guidelines to improve colorectal cancer care relevant to this country. The database will initially recruit all colorectal cancer cases from eight hospitals. The data will be stored on a customized web-based case report form. The database has begun collecting data from 1 October 2007 and will report on its first year findings at the end of 2008. PMID:19230248

  6. New registry: National Cancer Patient Registry--Colorectal Cancer.

    PubMed

    Wendy, L; Radzi, M

    2008-09-01

    Colorectal cancer is emerging as one of the commonest cancers in Malaysia. Data on colorectal cancer from the National Cancer Registry is very limited. Comprehensive information on all aspects of colorectal cancer, including demographic details, pathology and treatment outcome are needed as the management of colorectal cancer has evolved rapidly over the years involving several disciplines including gastroenterology, surgery, radiology, pathology and oncology. This registry will be an important source of information that can help the development of guidelines to improve colorectal cancer care relevant to this country. The database will initially recruit all colorectal cancer cases from eight hospitals. The data will be stored on a customized web-based case report form. The database has begun collecting data from 1 October 2007 and will report on its first year findings at the end of 2008.

  7. MicroRNAs: Clinical Relevance in Colorectal Cancer

    PubMed Central

    Thomas, Joe; Ohtsuka, Masahisa; Pichler, Martin; Ling, Hui

    2015-01-01

    Colorectal cancer is one of the most common cancer diagnoses and causes of mortality worldwide. MicroRNAs are a class of small, non-coding regulatory RNAs that have shown strong associations with colorectal cancer. Through the repression of target messenger RNAs, microRNAs modulate many cellular pathways, such as those involved in cell proliferation, apoptosis, and differentiation. The utilization of microRNAs has shown significant promise in the diagnosis and prognosis of colorectal cancer, owing to their unique expression profile associations with cancer types and malignancies. Moreover, microRNA therapeutics with mimics or antagonists show great promise in preclinical studies, which encourages further development of their clinical use for colorectal cancer patients. The unique ability of microRNAs to affect multiple downstream pathways represents a novel approach for cancer therapy. Although still early in its development, we believe that microRNAs can be used in the near future as biomarkers and therapeutic targets for colorectal cancer. PMID:26602923

  8. Treatment with Antiangiogenic Drugs in Multiple Lines in Patients with Metastatic Colorectal Cancer: Meta-Analysis of Randomized Trials.

    PubMed

    Hofheinz, R-D; Ronellenfitsch, U; Kubicka, S; Falcone, A; Burkholder, I; Hacker, U T

    2016-01-01

    Background. In metastatic colorectal cancer (mCRC), continuing antiangiogenic drugs beyond progression might provide clinical benefit. We synthesized the available evidence in a meta-analysis. Patients and Methods. We conducted a meta-analysis of studies investigating the use of antiangiogenic drugs beyond progression. Eligible studies were randomized phase II/III trials. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints were the impact of continuing antiangiogenic drugs (i) in subgroups, (ii) in different types of compounds targeting the VEGF-axis (monoclonal antibodies versus tyrosine kinase inhibitors), and (iii) on remission rates and prevention of progression. Results. Eight studies (3,668 patients) were included. Continuing antiangiogenic treatment beyond progression significantly improved PFS (HR 0.64; 95%-CI, 0.55-0.75) and OS (HR 0.83; 95%-CI, 0.76-0.89). PFS was significantly improved in all subgroups with comparable HR. OS was improved in all subgroups stratified by age, gender, and ECOG status. The rate of patients achieving at least stable disease was improved with an OR of 2.25 (95%-CI, 1.41-3.58). Conclusions. This analysis shows a significant PFS and OS benefit as well as a benefit regarding disease stabilization when using antiangiogenic drugs beyond progression in mCRC. Future studies should focus on the optimal sequence of administering antiangiogenic drugs. PMID:27656206

  9. Treatment with Antiangiogenic Drugs in Multiple Lines in Patients with Metastatic Colorectal Cancer: Meta-Analysis of Randomized Trials

    PubMed Central

    Kubicka, S.; Falcone, A.; Burkholder, I.; Hacker, U. T.

    2016-01-01

    Background. In metastatic colorectal cancer (mCRC), continuing antiangiogenic drugs beyond progression might provide clinical benefit. We synthesized the available evidence in a meta-analysis. Patients and Methods. We conducted a meta-analysis of studies investigating the use of antiangiogenic drugs beyond progression. Eligible studies were randomized phase II/III trials. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints were the impact of continuing antiangiogenic drugs (i) in subgroups, (ii) in different types of compounds targeting the VEGF-axis (monoclonal antibodies versus tyrosine kinase inhibitors), and (iii) on remission rates and prevention of progression. Results. Eight studies (3,668 patients) were included. Continuing antiangiogenic treatment beyond progression significantly improved PFS (HR 0.64; 95%-CI, 0.55–0.75) and OS (HR 0.83; 95%-CI, 0.76–0.89). PFS was significantly improved in all subgroups with comparable HR. OS was improved in all subgroups stratified by age, gender, and ECOG status. The rate of patients achieving at least stable disease was improved with an OR of 2.25 (95%-CI, 1.41–3.58). Conclusions. This analysis shows a significant PFS and OS benefit as well as a benefit regarding disease stabilization when using antiangiogenic drugs beyond progression in mCRC. Future studies should focus on the optimal sequence of administering antiangiogenic drugs. PMID:27656206

  10. Treatment with Antiangiogenic Drugs in Multiple Lines in Patients with Metastatic Colorectal Cancer: Meta-Analysis of Randomized Trials

    PubMed Central

    Kubicka, S.; Falcone, A.; Burkholder, I.; Hacker, U. T.

    2016-01-01

    Background. In metastatic colorectal cancer (mCRC), continuing antiangiogenic drugs beyond progression might provide clinical benefit. We synthesized the available evidence in a meta-analysis. Patients and Methods. We conducted a meta-analysis of studies investigating the use of antiangiogenic drugs beyond progression. Eligible studies were randomized phase II/III trials. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints were the impact of continuing antiangiogenic drugs (i) in subgroups, (ii) in different types of compounds targeting the VEGF-axis (monoclonal antibodies versus tyrosine kinase inhibitors), and (iii) on remission rates and prevention of progression. Results. Eight studies (3,668 patients) were included. Continuing antiangiogenic treatment beyond progression significantly improved PFS (HR 0.64; 95%-CI, 0.55–0.75) and OS (HR 0.83; 95%-CI, 0.76–0.89). PFS was significantly improved in all subgroups with comparable HR. OS was improved in all subgroups stratified by age, gender, and ECOG status. The rate of patients achieving at least stable disease was improved with an OR of 2.25 (95%-CI, 1.41–3.58). Conclusions. This analysis shows a significant PFS and OS benefit as well as a benefit regarding disease stabilization when using antiangiogenic drugs beyond progression in mCRC. Future studies should focus on the optimal sequence of administering antiangiogenic drugs.

  11. Strong correlation between diet and development of colorectal cancer.

    PubMed

    Cappellani, Alessandro; Zanghì, Antonio; Di Vita, Maria; Cavallaro, Andrea; Piccolo, Gaetano; Veroux, Pierfrancesco; Lo Menzo, Emanuele; Cavallaro, Vincenzo; de Paoli, Paolo; Veroux, Massimiliano; Berretta, Massimiliano

    2013-01-01

    Multiple factors have been described among the causes of non-hereditary colorectal cancer. In Western countries, the most common risk factors include upper-middle socioeconomic status and dietary regimens rich in proteins and animal fats. High consumption of red meats, smoked foods, cold cuts, or canned foods is believed to contribute to carcinogenesis as they directly affect epithlial turnover and cause metabolism of biliary acids. Dietary fibers have protective effects in that they capture the fats and biliary acids, thereby inhibiting their activity. Tobacco smoking acts both locally and systemically on the colorectal mucosa through the production of carcinogenic agents. Finally, the action of alcohol, in association with nicotine addiction, also increases the risk of developing colorectal tumors. Knowledge of dietary and environmental factors is of paramount importance in implementing preventive strategies for colorectal cancer. PMID:23276917

  12. Update on Hereditary Colorectal Cancer.

    PubMed

    DA Silva, Felipe Carneiro; Wernhoff, Patrik; Dominguez-Barrera, Constantino; Dominguez-Valentin, Mev

    2016-09-01

    In the past two decades, significant advances have been made in our understanding of colorectal (CRC) tumors with DNA mismatch (MMR) repair deficiency. The knowledge from molecular and genetic alterations in a variety of clinical conditions has refined the disease terminology and classification. Hereditary non-polyposis colorectal cancer (HNPCC) encompasses a spectrum of conditions that have significant phenotypic overlapping that makes clinical diagnosis a challenging task. Distinguishing among the HNPCC disorders is clinically important, as the approach to surveillance for patients and their at-risk family members differs according to risks for colonic and extracolonic cancer associated with each syndrome. Prospective and next-generation studies will provide valuable clinical information regarding the natural history of disease that will help differentiate the Lynch syndrome mimics and guide diagnosis and management for heterogeneous conditions currently grouped under the category of familial CRC. The review is intended to present and discuss the molecular nature of various conditions related to MMR deficiency and discusses the tools and strategies that have been used in detecting these conditions. PMID:27630275

  13. Genetic architecture of colorectal cancer.

    PubMed

    Peters, Ulrike; Bien, Stephanie; Zubair, Niha

    2015-10-01

    Colorectal cancer (CRC) is a complex disease that develops as a consequence of both genetic and environmental risk factors. A small proportion (3-5%) of cases arise from hereditary syndromes predisposing to early onset CRC as a result of mutations in over a dozen well defined genes. In contrast, CRC is predominantly a late onset 'sporadic' disease, developing in individuals with no obvious hereditary syndrome. In recent years, genome wide association studies have discovered that over 40 genetic regions are associated with weak effects on sporadic CRC, and it has been estimated that increasingly large genome wide scans will identify many additional novel genetic regions. Subsequent experimental validations have identified the causally related variant(s) in a limited number of these genetic regions. Further biological insight could be obtained through ethnically diverse study populations, larger genetic sequencing studies and development of higher throughput functional experiments. Along with inherited variation, integration of the tumour genome may shed light on the carcinogenic processes in CRC. In addition to summarising the genetic architecture of CRC, this review discusses genetic factors that modify environmental predictors of CRC, as well as examples of how genetic insight has improved clinical surveillance, prevention and treatment strategies. In summary, substantial progress has been made in uncovering the genetic architecture of CRC, and continued research efforts are expected to identify additional genetic risk factors that further our biological understanding of this disease. Subsequently these new insights will lead to improved treatment and prevention of colorectal cancer. PMID:26187503

  14. Targeted nanoparticles for colorectal cancer.

    PubMed

    Cisterna, Bruno A; Kamaly, Nazila; Choi, Won Il; Tavakkoli, Ali; Farokhzad, Omid C; Vilos, Cristian

    2016-09-01

    Colorectal cancer (CRC) is highly prevalent worldwide, and despite notable progress in treatment still leads to significant morbidity and mortality. The use of nanoparticles as a drug delivery system has become one of the most promising strategies for cancer therapy. Targeted nanoparticles could take advantage of differentially expressed molecules on the surface of tumor cells, providing effective release of cytotoxic drugs. Several efforts have recently reported the use of diverse molecules as ligands on the surface of nanoparticles to interact with the tumor cells, enabling the effective delivery of antitumor agents. Here, we present recent advances in targeted nanoparticles against CRC and discuss the promising use of ligands and cellular targets in potential strategies for the treatment of CRCs. PMID:27529192

  15. MicroRNA Methylation in Colorectal Cancer.

    PubMed

    Kaur, Sippy; Lotsari-Salomaa, Johanna E; Seppänen-Kaijansinkko, Riitta; Peltomäki, Päivi

    2016-01-01

    Epigenetic alterations such as DNA methylation, histone modifications and non-coding RNA (including microRNA) associated gene silencing have been identified as a major characteristic in human cancers. These alterations may occur more frequently than genetic mutations and play a key role in silencing tumor suppressor genes or activating oncogenes, thereby affecting multiple cellular processes. In recent years, studies have shown that microRNAs, that act as posttranscriptional regulators of gene expression are frequently deregulated in colorectal cancer (CRC), via aberrant DNA methylation. Over the past decade, technological advances have revolutionized the field of epigenetics and have led to the identification of numerous epigenetically dysregulated miRNAs in CRC, which are regulated by CpG island hypermethylation and DNA hypomethylation. In addition, aberrant DNA methylation of miRNA genes holds a great promise in several clinical applications such as biomarkers for early screening, prognosis, and therapeutic applications in CRC. PMID:27573897

  16. Dependence receptors and colorectal cancer.

    PubMed

    Mehlen, Patrick; Tauszig-Delamasure, Servane

    2014-11-01

    The research on colorectal cancer (CRC) biology has been leading the oncology field since the early 1990s. The search for genetic alterations has allowed the identification of the main tumour suppressors or oncogenes. Recent work obtained in CRC has unexpectedly proposed the existence of novel category of tumour suppressors, the so-called 'dependence receptors'. These transmembrane receptors behave as Dr Jekyll and Mr Hyde with two opposite sides: they induce a positive signalling (survival, proliferation, differentiation) in presence of their ligand, but are not inactive in the absence of their ligand and rather trigger apoptosis when unbound. This trait confers them a conditional tumour suppressor activity: they eliminate cells that grow abnormally in an environment offering a limited quantity of ligand. This review will describe how receptors such as deleted in colorectal carcinoma (DCC), uncoordinated 5 (UNC5), rearranged during transfection (RET) or TrkC constrain CRC progression and how this dependence receptor paradigm may open up therapeutical perspectives. PMID:25163468

  17. Temporal relationship between prostate brachytherapy and the diagnosis of colorectal cancer

    SciTech Connect

    Gutman, Sarah A.; Merrick, Gregory S. . E-mail: gmerrick@urologicresearchinstitute.org; Butler, Wayne M.; Wallner, Kent E.; Allen, Zachariah A.; Galbreath, Robert W.; Adamovich, Edward

    2006-09-01

    Purpose: To identify the location of pretreatment and posttreatment colorectal malignancies and posttreatment colorectal polyps in patients with clinically localized prostate cancer managed with brachytherapy. Methods and Materials: From April 1995 through July 2004, 1,351 consecutive patients underwent brachytherapy for clinical stage T1b-T3a (American Joint Committee on Cancer, 2002) prostate cancer. Supplemental external beam radiotherapy (XRT) was administered to 699 patients. The median follow-up was 4.6 years. Operative and pathology reports were reviewed for all patients with pretreatment and posttreatment colorectal cancer and posttreatment colorectal polyps. Multiple parameters were evaluated for the development of colorectal cancer or colorectal polyps. Results: Colorectal cancer was diagnosed in 23 and 25 patients before and after prostate brachytherapy, respectively. No differences were identified in the distribution of colorectal cancers either before or after treatment (3 and 4 rectal cancers in the pre- and postbrachytherapy cohorts). Thirty-five of the 48 colorectal cancers (73%) were diagnosed within 5 years of brachytherapy with a peak incidence 1 year after brachytherapy. One hundred ninety-two colorectal polyps were diagnosed after brachytherapy, 160 (83%) occurred within 4 years of brachytherapy, and only 27 (14%) were located in the rectum. In multivariate Cox regression analysis, prostate D{sub 9} (minimum percentage of the dose covering 90% of the target volume) predicted for posttreatment colorectal cancer. Rectal polyps were most closely related to patient age and percent positive biopsies, whereas sigmoid/colon polyps were best predicted by patient age, planning volume, and supplemental XRT. Conclusions: Colorectal cancer was diagnosed with equal frequency before and after brachytherapy with comparable geographic distributions. In addition, the vast majority of postbrachytherapy colorectal polyps were located beyond the confines of the

  18. Tests to Detect Colorectal Cancer and Polyps

    MedlinePlus

    ... be acceptable screening tests for colorectal cancer: High-sensitivity fecal occult blood tests (FOBT). Both polyps and ... higher than that of gFOBT or FIT. Test sensitivity for adenomas is low. False-positive test results ...

  19. TAS-102 for Metastatic Colorectal Cancer

    Cancer.gov

    A summary of results from an international phase III trial that compared TAS-102 with placebo in patients with metastatic colorectal cancer whose disease progressed following prior treatments or who had health conditions that prevented the re-administrati

  20. Diet, microbiota, and colorectal cancer.

    PubMed

    Akin, Hakan; Tözün, Nurdan

    2014-01-01

    Colorectal cancer (CRC) is the third most common cancer in the world causing nearly 500,000 deaths every year. In addition to genetic background, environmental factors including diet and lifestyle are accepted as major contributors to adenoma and CRC development. Lifestyle factors include high BMI, obesity, and reduced physical activity. Growing interest and accumulating data on human microbiota implicate that host-microbe interplay has an important role in the development of metabolic, neoplastic, and inflammatory diseases. Findings from recent studies suggest that colon cancer risk is determined by the interaction between diet and gut microbiota. Dietary changes affect gut microbiota and conversely microbiota mediates the generation of dietary factors triggering colon cancer. Identification of the microbial communities associated with carcinogenesis is of crucial importance. Nowadays, with the evolvement of culture-independent molecular techniques, it has become possible to identify main bacterial species in healthy individuals, inflammatory conditions, and CRC. Some recent studies have shown the differences in intestinal microbiota between colon cancer patients and healthy individuals. Animal studies have provided a better understanding of interaction between pathobionts and symbionts in the development of colon cancer. There is no single causative organism identified in CRC; however, there is strong evidence that reduction of protective bacteria, increase in some bacteria (ie, fusobacterium members; Bacteroides/Prevotella), and age-related changes in microbiota have an impact on adenoma or cancer development. Future studies will enable us to understand procarcinogenic and anticarcinogenic mechanisms and give insights to rational manipulation of the microbiota with prebiotics, probiotics, or dietary modifications. PMID:25291132

  1. The stability of colorectal cancer mathematical models

    NASA Astrophysics Data System (ADS)

    Khairudin, Nur Izzati; Abdullah, Farah Aini

    2013-04-01

    Colorectal cancer is one of the most common types of cancer. To better understand about the kinetics of cancer growth, mathematical models are used to provide insight into the progression of this natural process which enables physicians and oncologists to determine optimal radiation and chemotherapy schedules and develop a prognosis, both of which are indispensable for treating cancer. This thesis investigates the stability of colorectal cancer mathematical models. We found that continuous saturating feedback is the best available model of colorectal cancer growth. We also performed stability analysis. The result shows that cancer progress in sequence of genetic mutations or epigenetic which lead to a very large number of cells population until become unbounded. The cell population growth initiate and its saturating feedback is overcome when mutation changes causing the net per-capita growth rate of stem or transit cells exceed critical threshold.

  2. Abdominal metastases from colorectal cancer: intraperitoneal therapy

    PubMed Central

    Guend, Hamza; Patel, Sunil

    2015-01-01

    Patients with peritoneal metastasis from colorectal cancer represent a distinct subset with regional disease rather than systemic disease. They often have poorer survival outcomes with systemic chemotherapy. Optimal cytoreductive surgery and intraperitoneal chemotherapy (IPC) offers such patients a more directed therapy with improved survival. In this review, we discuss the diagnosis, evaluation and classification, as well as rational for treatment of peritoneal carcinomatosis (PC) secondary to colorectal cancer. PMID:26697203

  3. Industrial risk factors for colorectal cancer

    SciTech Connect

    Lashner, B.A.; Epstein, S.S. )

    1990-01-01

    Colorectal cancer is the second most common malignancy in the United States, and its incidence rates have sharply increased recently, especially in males. Industrial exposures, both occupational and environmental, are important colorectal cancer risk factors that are generally unrecognized by clinicians. Migration studies have documented that colorectal cancer is strongly associated with environmental risk factors. The causal role of occupational exposures is evidenced by a substantial literature associating specific work practices with increased colorectal cancer risks. Industrially related environmental exposures, including polluted drinking water and ionizing radiation, have also been associated with excess risks. Currently, there is a tendency to attribute colorectal cancer, largely or exclusively, to dietary and other lifestyle factors, thus neglecting these industrially related effects. Concerted efforts are needed to recognize the causal role of industrial risk factors and to encourage government and industry to reduce carcinogenic exposures. Furthermore, cost-effective screening programs for high-risk population groups are critically needed to further reduce deaths from colorectal cancer. 143 references.

  4. Targeting mTOR network in colorectal cancer therapy

    PubMed Central

    Wang, Xiao-Wen; Zhang, Yan-Jie

    2014-01-01

    The mechanistic target of rapamycin (mTOR) integrates growth factor signals with cellular nutrient and energy levels and coordinates cell growth, proliferation and survival. A regulatory network with multiple feedback loops has evolved to ensure the exquisite regulation of cell growth and division. Colorectal cancer is the most intensively studied cancer because of its high incidence and mortality rate. Multiple genetic alterations are involved in colorectal carcinogenesis, including oncogenic Ras activation, phosphatidylinositol 3-kinase pathway hyperactivation, p53 mutation, and dysregulation of wnt pathway. Many oncogenic pathways activate the mTOR pathway. mTOR has emerged as an effective target for colorectal cancer therapy. In vitro and preclinical studies targeting the mTOR pathway for colorectal cancer chemotherapy have provided promising perspectives. However, the overall objective response rates in major solid tumors achieved with single-agent rapalog therapy have been modest, especially in advanced metastatic colorectal cancer. Combination regimens of mTOR inhibitor with agents such as cytotoxic chemotherapy, inhibitors of vascular endothelial growth factor, epidermal growth factor receptor and Mitogen-activated protein kinase kinase (MEK) inhibitors are being intensively studied and appear to be promising. Further understanding of the molecular mechanism in mTOR signaling network is needed to develop optimized therapeutic regimens. In this paper, oncogenic gene alterations in colorectal cancer, as well as their interaction with the mTOR pathway, are systematically summarized. The most recent preclinical and clinical anticancer therapeutic endeavors are reviewed. New players in mTOR signaling pathway, such as non-steroidal anti-inflammatory drug and metformin with therapeutic potentials are also discussed here. PMID:24764656

  5. Precancerous Lesions in Colorectal Cancer

    PubMed Central

    Sandouk, Fayez; Al Jerf, Feras; Al-Halabi, M. H. D. Bassel

    2013-01-01

    Colorectal cancer (CRC) is the third most common cause of cancer death in the world. The incidence rate (ASR) and age distribution of this disease differ between most of African-Middle-Eastern (AMAGE) and North America and Europe for many reasons. However, in all areas, “CRC” is considered as one of the most preventable cancers, because it might develop from variant processes like polyps and IBD in addition to the genetic pathogenesis which became very well known in this disease. We tried in this paper to review all the possible reasons of the differences in incidence and age between the west and AMAGE. Also we reviewed all the mutations that lead to the hereditary and familiar clustering of this disease with the correlations with the surrounding food and environment of different areas. Then, we focused on the precancerous pathology of this disease with special focusing on early detection depending on new endoscopy technology and most important genetic studies. We lastly reviewed the evidence of some of the surveillance and put suggestions about future surveillance programs and how important those programs are on the psychological aspect of the patients and their families. PMID:23737765

  6. Nutritional status assessment in colorectal cancer patients.

    PubMed

    Lopes, Joana Pedro; de Castro Cardoso Pereira, Paula Manuela; dos Reis Baltazar Vicente, Ana Filipa; Bernardo, Alexandra; de Mesquita, María Fernanda

    2013-01-01

    The present study intended to evaluate the nutritional status of Portuguese colorectal patients and associated it with surgery type as well as quality of life outcomes. Malnutrition can affect up to 85% of cancer patients and specifically 30-60% in colorectal cancer and can significantly influence health outcomes. A sample of 50 colorectal cancer patients was evaluated in what refers to several anthropometric measures, food intake, clinical history, complications rate before and after surgery procedure. The sample was divided between convention and fast-track procedures. Most of the individuals were overweight or obese but had lost weight on the past six months. Despite mild, there were signs of malnutrition in this sample with high losses of fat free mass, weight and also fat mass during the hospitalization period. These results reinforce the importance of malnutrition assessment in colorectal patients as well as consider weight loss on the past months and body composition in order to complement nutritional status evaluation.

  7. Genetics of Colorectal Cancer (PDQ®)—Health Professional Version

    Cancer.gov

    Expert-reviewed information summary about the genetics of colorectal cancer, including information about specific genes and family cancer syndromes. The summary also contains information about screening for colorectal cancer and research aimed at prevention of this disease. Psychosocial issues associated with genetic testing and counseling of individuals who may have hereditary colorectal cancer syndrome are also discussed.

  8. Colorectal cancer, diabetes and survival: epidemiological insights.

    PubMed

    Zanders, M M J; Vissers, P A J; Haak, H R; van de Poll-Franse, L V

    2014-04-01

    Colorectal cancer (CRC) patients with pre-existing diabetes have significantly lower rates of overall survival compared with patients without diabetes. Against this backdrop, the American Diabetes Association and American Cancer Society in 2010 reviewed the scientific literature concerning diabetes and cancer. One of the key issues identified for further investigation was the need for a better understanding of whether diabetes influences cancer prognosis above and beyond the prognosis conferred by each disease state independently. Whether the worsened survival of CRC patients with diabetes could be explained by less favourable patient-, tumour- and treatment-related characteristics has also been evaluated in numerous recent studies. However, as most studies did not account for all the various potential confounders, such as cancer stage, comorbidities and body mass index (BMI) in their analyses, the current evidence for the association between diabetes and survival in CRC patients remains inconclusive. Nevertheless, based on multiple examples in the literature, the present review demonstrates that diabetes affects the presentation of CRC as well as its treatment and outcome, which may then result in lower overall rates of survival in patients with, compared to those without, diabetes. PMID:24507584

  9. Radiotherapy and brachytherapy for recurrent colorectal cancer

    SciTech Connect

    Nag, S. )

    1991-05-01

    Radical surgical excision of locoregional recurrence of colorectal carcinoma usually produces the best survival and should be attempted whenever possible. However, recurrences are often unresectable; hence palliative local therapy may be indicated. There are several options for the radiation therapy of local, unresectable, recurrent, or metastatic colorectal cancer. Whole pelvis irradiation of 4,000-5,000 cGy followed by a coned-down boost of 1,000-1,500 cGy generally provides good symptomatic palliation in 80-90% of patients, but long-term control or cure is rarely achieved. External beam irradiation of 2,000-3,000 cGy to the whole liver with or without concurrent chemotherapy may be used for palliation of metastatic disease to the liver. A combination of intraoperative radiation therapy applied directly to the tumor bed and external beam irradiation may improve local control and survival rates. Multiple options are available for the intraoperative use of brachytherapy which can deliver high radiation doses to the residual tumor, or tumor bed, sparing normal tissue.

  10. [Colorectal cancer (CCR): genetic and molecular alterations].

    PubMed

    Juárez-Vázquez, Clara Ibet; Rosales-Reynoso, Mónica Alejandra

    2014-01-01

    The aim of this review is to present a genetic and molecular overview of colorectal carcinogenesis (sporadic and hereditary origin) as a multistage process, where there are a number of molecular mechanisms associated with the development of colorectal cancer and genomic instability that allows the accumulation of mutations in proto-oncogenes and tumor suppressor genes, chromosomal instability, and methylation and microsatellite instability, and the involvement of altered expression of microRNAs' prognosis factors.

  11. Tissue Specific Promoters in Colorectal Cancer

    PubMed Central

    Rama, A. R.; Aguilera, A.; Melguizo, C.; Caba, O.; Prados, J.

    2015-01-01

    Colorectal carcinoma is the third most prevalent cancer in the world. In the most advanced stages, the use of chemotherapy induces a poor response and is usually accompanied by other tissue damage. Significant progress based on suicide gene therapy has demonstrated that it may potentiate the classical cytotoxic effects in colorectal cancer. The inconvenience still rests with the targeting and the specificity efficiency. The main target of gene therapy is to achieve an effective vehicle to hand over therapeutic genes safely into specific cells. One possibility is the use of tumor-specific promoters overexpressed in cancers. They could induce a specific expression of therapeutic genes in a given tumor, increasing their localized activity. Several promoters have been assayed into direct suicide genes to cancer cells. This review discusses the current status of specific tumor-promoters and their great potential in colorectal carcinoma treatment. PMID:26648599

  12. Gut microbiota imbalance and colorectal cancer

    PubMed Central

    Gagnière, Johan; Raisch, Jennifer; Veziant, Julie; Barnich, Nicolas; Bonnet, Richard; Buc, Emmanuel; Bringer, Marie-Agnès; Pezet, Denis; Bonnet, Mathilde

    2016-01-01

    The gut microbiota acts as a real organ. The symbiotic interactions between resident micro-organisms and the digestive tract highly contribute to maintain the gut homeostasis. However, alterations to the microbiome caused by environmental changes (e.g., infection, diet and/or lifestyle) can disturb this symbiotic relationship and promote disease, such as inflammatory bowel diseases and cancer. Colorectal cancer is a complex association of tumoral cells, non-neoplastic cells and a large amount of micro-organisms, and the involvement of the microbiota in colorectal carcinogenesis is becoming increasingly clear. Indeed, many changes in the bacterial composition of the gut microbiota have been reported in colorectal cancer, suggesting a major role of dysbiosis in colorectal carcinogenesis. Some bacterial species have been identified and suspected to play a role in colorectal carcinogenesis, such as Streptococcus bovis, Helicobacter pylori, Bacteroides fragilis, Enterococcus faecalis, Clostridium septicum, Fusobacterium spp. and Escherichia coli. The potential pro-carcinogenic effects of these bacteria are now better understood. In this review, we discuss the possible links between the bacterial microbiota and colorectal carcinogenesis, focusing on dysbiosis and the potential pro-carcinogenic properties of bacteria, such as genotoxicity and other virulence factors, inflammation, host defenses modulation, bacterial-derived metabolism, oxidative stress and anti-oxidative defenses modulation. We lastly describe how bacterial microbiota modifications could represent novel prognosis markers and/or targets for innovative therapeutic strategies. PMID:26811603

  13. Colorectal Cancer Rates by Race and Ethnicity

    MedlinePlus

    ... getting colorectal cancer, followed by white, Hispanic, Asian/Pacific Islander (A/PI), and American Indian/Alaska Native ( ... white, Hispanic, American Indian/Alaska Native, and Asian/Pacific Islander women. Sources: CDC’s National Program of Cancer ...

  14. Diagnostics and Epidemiology of Colorectal Cancer.

    PubMed

    Kolligs, Frank T

    2016-06-01

    Colorectal cancer is one of the leading causes of cancer-related morbidity and mortality. Main risk factors include advanced age, family history, male sex, and lifestyle factors. Screening can reduce incidence and death from colorectal cancer. Therefore, prevention and early detection are crucial in order to detect and remove pre-neoplastic adenomas and to detect cancers at early stages. Colonoscopy, flexible sigmoidoscopy, and fecal occult blood tests are established tools for screening. Newer fecal immunochemical tests reveal higher sensitivities for advanced adenoma and cancer than guaiac-based hemoccult tests. Molecular stool and blood tests as well as virtual colonoscopy and colon capsule endoscopy are promising new developments so far not established as routine instruments for the prevention and early detection of colorectal cancer. Colonoscopy is the method of choice for the diagnosis of colorectal cancer and for adenoma removal. Prognosis is essentially dependent on the tumor stage at the time of the initial diagnosis. Proper staging based on imaging prior to therapy is a prerequisite. In rectal cancer, local staging is an essential requirement for the identification of appropriate candidates for neoadjuvant therapy. PMID:27493942

  15. Metastatic colorectal cancer in a cirrhotic liver with synchronous hepatocellular carcinoma.

    PubMed

    Karass, Michael; Grossniklaus, Emily; Seoud, Talal; Kamel, Ralph; Teniola, Oluwadamilola; Oprea, Gabriela; Goldstein, Daniel A; Jain, Sanjay

    2015-11-01

    We are reporting a case of a patient with a previous history of colorectal cancer (CRC) and cirrhosis, who developed concurrent liver lesions consistent with hepatocellular carcinoma (HCC); a case which is unique due to the low incidence of multiple cancers, particularly HCC in the setting of previous advanced colorectal carcinoma along, in a cirrhotic liver. We will review the known literature on multiple cancer rates found in patients with known colorectal carcinoma. We will then outline this particular patient's presentation, followed by a discussion as to why the particular concurrent development of HCC in the setting of previous CRC is of note.

  16. Fruit and vegetable intakes and risk of colorectal cancer and incident and recurrent adenomas in the PLCO cancer screening trial.

    PubMed

    Kunzmann, Andrew T; Coleman, Helen G; Huang, Wen-Yi; Cantwell, Marie M; Kitahara, Cari M; Berndt, Sonja I

    2016-04-15

    The roles of fruits and vegetables in colorectal cancer development are unclear. Few prospective studies have assessed the association with adenoma, a known precursor to colorectal cancer. Our aim was to evaluate the association between fruit and vegetable intake and colorectal cancer development by evaluating the risk of incident and recurrent colorectal adenoma and colorectal cancer. Study participants were identified from the intervention arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Fruit and vegetable intake was measured using a self-reported dietary questionnaire. Total fruit and vegetable intake was not associated with reduced incident or recurrent adenoma risk overall, but a protective association was observed for multiple adenomas (Odds ratio 3rd tertile vs. 1st tertile = 0.61, 95% confidence interval (CI): 0.38, 1.00). Higher fruit and vegetable intakes were associated with a borderline reduced risk of colorectal cancer (Hazard ratio (HR) 3rd tertile vs. 1st tertile = 0.82, 95% CI: 0.67, 1.01), which reached significance amongst individuals with high processed meat intakes (HR = 0.74, 95% CI: 0.55, 0.99). Our results suggest that increased fruit and vegetable intake may protect against multiple adenoma development and may reduce the detrimental effects of high processed meat intakes on colorectal cancer risk.

  17. Relationship between intestinal microbiota and colorectal cancer

    PubMed Central

    Cipe, Gokhan; Idiz, Ufuk Oguz; Firat, Deniz; Bektasoglu, Huseyin

    2015-01-01

    The human gastrointestinal tract hosts a complex and vast microbial community with up to 1011-1012 microorganisms colonizing the colon. The gut microbiota has a serious effect on homeostasis and pathogenesis through a number of mechanisms. In recent years, the relationship between the intestinal microbiota and sporadic colorectal cancer has attracted much scientific interest. Mechanisms underlying colonic carcinogenesis include the conversion of procarcinogenic diet-related factors to carcinogens and the stimulation of procarcinogenic signaling pathways in luminal epithelial cells. Understanding each of these mechanisms will facilitate future studies, leading to the development of novel strategies for the diagnosis, treatment, and prevention of colorectal cancer. In this review, we discuss the relationship between colorectal cancer and the intestinal microbiota. PMID:26483877

  18. Advanced endoscopic technologies for colorectal cancer screening

    PubMed Central

    Obstein, Keith L; Valdastri, Pietro

    2013-01-01

    Colorectal cancer is the third most common cancer in men and the second most common cancer in women worldwide. Diagnosing colorectal has been increasingly successful due to advances in technology. Flexible endoscopy is considered to be an effective method for early diagnosis and treatment of gastrointestinal cancer, making it a popular choice for screening programs. However, millions of people who may benefit from endoscopic colorectal cancer screening fail to have the procedure performed. Main reasons include psychological barriers due to the indignity of the procedure, fear of procedure related pain, bowel preparation discomfort, and potential need for sedation. Therefore, an urgent need for new technologies addressing these issues clearly exists. In this review, we discuss a set of advanced endoscopic technologies for colorectal cancer screening that are either already available or close to clinical trial. In particular, we focus on visual-inspection-only advanced flexible colonoscopes, interventional colonoscopes with alternative propulsion mechanisms, wireless capsule colonoscopy, and technologies for intraprocedural bowel cleansing. Many of these devices have the potential to reduce exam related patient discomfort, obviate the need for sedation, increase diagnostic yield, reduce learning curves, improve access to screening, and possibly avert the need for a bowel preparation. PMID:23382621

  19. Local inflammatory response in colorectal cancer.

    PubMed

    Łaskowski, P; Klim, B; Ostrowski, K; Szkudlarek, M; Litwiejko-Pietryńczak, E; Kitlas, K; Nienartowicz, S; Dzięcioł, J

    2016-06-01

    Type and intensity of tumor-infiltrating lymphocytes (TILs) in close proximity to the primary tumor are prognostically significant in postoperative patients. High intensity of TILs is considered to be a prognostically beneficial factor. The research included 66 postoperative colorectal cancer patients. The control group comprised 20 colon segments. Monoclonal antibodies LCA, CD3, CD4, CD5, CD8, CD20, CD23 and CD138 were used to differentiate between T and B lymphocytes. Types of cells in the infiltrate were defined. We found greater numbers of T and B lymphocytes located in close proximity to the cancerous tissue when compared to the control group. T lymphocyte intensity in the inflammatory infiltrations was directly correlated with the size of resected tumors, presence of regional lymphatic node metastases and histological grade of malignancy. Lymphocytic infiltrations of greater intensity located in close proximity to the primary tumor were found in subjects with less advanced colorectal cancer. The research presented here proves direct dependence between the immune system and colorectal cancer. The presence of lymphocytes in the inflammatory infiltrations located in close proximity to the cancerous tissue has been proved to be prognostically beneficial. The obtained results support the application of immunotherapy in colorectal cancer treatment. PMID:27543872

  20. [New advances in hereditary colorectal cancer].

    PubMed

    Moreira, Leticia

    2015-09-01

    Colorectal cancer is the most frequent malignancy in both sexes in Spain. Between 20% and 25% of affected individuals have a family history of the disease, and 5% to 6% have a germ mutation, i.e. the disease develops in the context of a hereditary syndrome. The importance of identifying patients with hereditary syndromes predisposing them to colorectal cancer lies in the possibility of applying preventive measures, screening, and more appropriate management of both patients and their families. The present article outlines the most important studies presented at the congress of the American Gastroenterological Association.

  1. Surgical quality in colorectal cancer

    PubMed Central

    Plummer, Joseph M.; Williams, Nadia; Leake, Pierre-Anthony; Ferron-Boothe, Doreen; Meeks-Aitken, Nicola; Mitchell, Derek I.; McFarlane, Michael E.; East, Jeffery

    2015-01-01

    Objective To determine the quality of surgical management offered to patients with colorectal cancer (CRC) as measured by adequacy of nodal resections and compare variations across the major hospitals in Jamaica. Method Data was obtained from the CRC Registry of patients diagnosed and treated surgically for CRC during the 3-year period commencing January 1, 2011. Variables analyzed included tumor site, stage and number of lymph nodes resected across hospitals. Results During the period under review 60% (349) of 586 patients had resections and formed the basis of this study. Of these 49% were treated at the UHWI, 27% from the KPH and STH, 15% from CRH and MRH and 8% from a private laboratory (DPS). Patient distribution was similar at UHWI compared to the others with mean age (61 vs 62) and with slightly more women having surgery (53% Vs 54%) (UHWI vs Others). For tumor grade, margin status, lymphovascular and depth of invasion (majority T3) there was no difference between UHWI and the other sites, although a smaller percentage of tumors treated at UHWI had Crohn's like reaction (p = 0.01). There was a larger proportion of sigmoid cancer at UHWI while the reverse trend was seen in cancers of the rectum (p = 0.027). The tumors treated at UHWI have a larger median number of regional nodes when compared to the other facilities (14 vs 10; p < 0.001) and also more likely to have positive nodes, as were women and younger patients. Comparison across facilities revealed that the proportion of tumors classed as well differentiated, circumferential margin involvement, and having lymphovascular invasion were higher for specimens processed at the private facility (p = 0.021, 0.035, 0.01 respectively). Histopathology reports of tumors treated at UHWI and DPS had median 14 and 18 nodes respectively while at NPH laboratory and CRH they were 9 and 10 respectively (p < 0.001), whilst those of the ascending, descending, sigmoid colon and rectum had median 15, 11, 13, 11

  2. Get Tested for Colorectal Cancer

    MedlinePlus

    ... of fiber . Talk with your doctor about taking aspirin every day. Taking aspirin every day can lower your risk of colorectal ... 50 to 59, ask your doctor if daily aspirin is right for you . Previous section Get Tested ...

  3. Targeting of multiple oncogenic signaling pathways by Hsp90 inhibitor alone or in combination with berberine for treatment of colorectal cancer.

    PubMed

    Su, Yen-Hao; Tang, Wan-Chun; Cheng, Ya-Wen; Sia, Peik; Huang, Chi-Chen; Lee, Yi-Chao; Jiang, Hsin-Yi; Wu, Ming-Heng; Lai, I-Lu; Lee, Jun-Wei; Lee, Kuen-Haur

    2015-10-01

    There is a wide range of drugs and combinations under investigation and/or approved over the last decade to treat colorectal cancer (CRC), but the 5-year survival rate remains poor at stages II-IV. Therefore, new, more-efficient drugs still need to be developed that will hopefully be included in first-line therapy or overcome resistance when it appears, as part of second- or third-line treatments in the near future. In this study, we revealed that heat shock protein 90 (Hsp90) inhibitors have high therapeutic potential in CRC according to combinative analysis of NCBI's Gene Expression Omnibus (GEO) repository and chemical genomic database of Connectivity Map (CMap). We found that second generation Hsp90 inhibitor, NVP-AUY922, significantly downregulated the activities of a broad spectrum of kinases involved in regulating cell growth arrest and death of NVP-AUY922-sensitive CRC cells. To overcome NVP-AUY922-induced upregulation of survivin expression which causes drug insensitivity, we found that combining berberine (BBR), a herbal medicine with potency in inhibiting survivin expression, with NVP-AUY922 resulted in synergistic antiproliferative effects for NVP-AUY922-sensitive and -insensitive CRC cells. Furthermore, we demonstrated that treatment of NVP-AUY922-insensitive CRC cells with the combination of NVP-AUY922 and BBR caused cell growth arrest through inhibiting CDK4 expression and induction of microRNA-296-5p (miR-296-5p)-mediated suppression of Pin1-β-catenin-cyclin D1 signaling pathway. Finally, we found that the expression level of Hsp90 in tumor tissues of CRC was positively correlated with CDK4 and Pin1 expression levels. Taken together, these results indicate that combination of NVP-AUY922 and BBR therapy can inhibit multiple oncogenic signaling pathways of CRC. PMID:25982393

  4. Gut Microbiota, Inflammation, and Colorectal Cancer.

    PubMed

    Brennan, Caitlin A; Garrett, Wendy S

    2016-09-01

    Colorectal cancer is the second-leading cause of cancer-related deaths in the United States and fourth-leading cause of cancer-related deaths worldwide. While cancer is largely considered to be a disease of genetic and environmental factors, increasing evidence has demonstrated a role for the microbiota (the microorganisms associated with the human body) in shaping inflammatory environments and promoting tumor growth and spread. Herein, we discuss both human data from meta'omics analyses and data from mechanistic studies in cell culture and animal models that support specific bacterial agents as potentiators of tumorigenesis-including Fusobacterium nucleatum, enterotoxigenic Bacteroides fragilis, and colibactin-producing Escherichia coli. Further, we consider how microbes can be used in diagnosing colorectal cancer and manipulating the tumor environment to encourage better patient outcomes in response to immunotherapy treatments. PMID:27607555

  5. Colorectal Cancer and Basement Membranes: Clinicopathological Correlations

    PubMed Central

    Mylonas, Charalampos C.; Lazaris, Andreas C.

    2014-01-01

    Colorectal cancer (CRC) is the third most commonly diagnosed cancer in males and the second in females. In 2008, an estimated 1.2 million people were diagnosed with and 608,700 people died of CRC. Besides diagnosis and treatment, prognosis is an important matter for cancer patients. Today, clinicopathological correlations have many applications in cancer prognostication. Examples include the prediction of the medium patient survival and the screening for patients suitable for specific therapeutic approaches. Apart from traditional prognostic factors, such as tumor stage and grade, new markers may be useful in clinical practice. Possible markers may result from the study of basement membranes (BMs). BM seems to play a role in the pathogenesis of colorectal cancer, so BM alterations may have prognostic significance as well. The purpose of this review is to briefly describe BMs and their relationship with CRC, in the aspect of clinicopathological correlations. PMID:25614736

  6. Pleiotropic effects of genetic risk variants for other cancers on colorectal cancer risk: PAGE, GECCO, and CCFR Consortia

    PubMed Central

    Cheng, Iona; Kocarnik, Jonathan M; Dumitrescu, Logan; Lindor, Noralane M; Chang-Claude, Jenny; Avery, Christy L.; Caberto, Christian P; Love, Shelly-Ann; Slattery, Martha L; Chan, Andrew T; Baron, John A; Hindorff, Lucia A; Park, Sungshim Lani; Schumacher, Fredrick R; Hoffmeister, Michael; Kraft, Peter; Butler, Anne; Duggan, David; Hou, Lifang; Carlson, Chris S; Monroe, Kristine R; Lin, Yi; Carty, Cara L; Mann, Sue; Ma, Jing; Giovannucci, Edward L; Fuchs, Charles S; Newcomb, Polly A; Jenkins, Mark A; Hopper, John L; Haile, Robert W; Conti, David V; Campbell, Peter T; Potter, John D; Caan, Bette J; Schoen, Robert E; Hayes, Richard B; Chanock, Stephen J; Berndt, Sonja I; Kury, Sebastien; Bezieau, Stephane; Ambite, Jose Luis; Kumaraguruparan, Gowri; Richardson, Danielle; Goodloe, Robert J; Dilks, Holli H; Baker, Paxton; Zanke, Brent W; Lemire, Mathieu; Gallinger, Steven; Hsu, Li; Jiao, Shuo; Harrison, Tabitha; Seminara, Daniela; Haiman, Christopher A; Kooperberg, Charles; Wilkens, Lynne R; Hutter, Carolyn M; White, Emily; Crawford, Dana C; Heiss, Gerardo; Hudson, Thomas J; Brenner, Hermann; Bush, William S; Casey, Graham; Marchand, Loic Le; Peters, Ulrike

    2013-01-01

    Objective Genome-wide association studies (GWAS) have identified a large number of single nucleotide polymorphisms (SNPs) associated with a wide array of cancer sites. Several of these variants demonstrate associations with multiple cancers, suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesized that SNPs previously associated with other cancers may additionally be associated with colorectal cancer. In a large-scale study, we examined 171 SNPs previously associated with 18 different cancers for their associations with colorectal cancer. Design We examined 13,338 colorectal cancer cases and 40,967 controls from three consortia: Population Architecture using Genetics and Epidemiology (PAGE), Genetic Epidemiology of Colorectal Cancer (GECCO), and the Colon Cancer Family Registry (CCFR). Study-specific logistic regression results, adjusted for age, sex, principal components of genetic ancestry, and/or study specific factors (as relevant) were combined using fixed-effect meta-analyses to evaluate the association between each SNP and colorectal cancer risk. A Bonferroni-corrected p-value of 2.92×10−4 was used to determine statistical significance of the associations. Results Two correlated SNPs— rs10090154 and rs4242382—in Region 1 of chromosome 8q24, a prostate cancer susceptibility region, demonstrated statistically significant associations with colorectal cancer risk. The most significant association was observed with rs4242382 (meta-analysis OR=1.12; 95% CI: 1.07–1.18; P=1.74×10−5), which also demonstrated similar associations across racial/ethnic populations and anatomical sub-sites. Conclusion This is the first study to clearly demonstrate Region 1 of chromosome 8q24 as a susceptibility locus for colorectal cancer, thus adding colorectal cancer to the list of cancer sites linked to this particular multi-cancer risk region at 8q24. PMID:23935004

  7. Hyperplastic polyposis: association with colorectal cancer.

    PubMed

    Leggett, B A; Devereaux, B; Biden, K; Searle, J; Young, J; Jass, J

    2001-02-01

    Hyperplastic polyposis is a loosely defined syndrome initially thought not to confer a clinically important predisposition to colorectal cancer. The aim of the current study was to examine the clinical, histologic, and molecular features of a prospective series of cases meeting a strict definition of the condition. Twelve patients were identified, seven of whom had developed colorectal cancer. Most polyps were hyperplastic, but 11 patients also had polyps containing dysplasia as either serrated adenomas. mixed polyps, or traditional adenomas. The mean percentage of dysplastic polyps in patients with cancer was 35%, and in patients without cancer, 11% (p < 0.05). Microsatellite instability (MSI) was present in 3 of 47 hyperplastic polyps and two of eight serrated adenomas. Kras was mutated in 8 of 47 hyperplastic polyps and two of eight serrated adenomas. No polyps showed loss of heterozygosity of chromosomes 5q, 1p, or 18q. Two of seven cancers showed a high level of MSI. It is concluded that hyperplastic polyposis is associated with a high risk of colorectal cancer. Hyperplastic polyps are the dominant type of polyp, but most cases have some dysplastic epithelium. A higher proportion of dysplastic polyps is associated with increased cancer risk. Clonal genetic changes are observed in some hyperplastic polyps and serrated adenomas.

  8. Missense Polymorphisms in the Adenomatous Polyposis Coli Gene and Colorectal Cancer Risk

    PubMed Central

    Cleary, Sean P.; Kim, Hyeja; Croitoru, Marina E.; Redston, Mark; Knight, Julia A.; Gallinger, Steven; Gryfe, Robert

    2009-01-01

    PURPOSE Whereas truncating germline mutations of the adenomatous polyposis coli (APC) gene give rise to familial adenomatous polyposis, missense polymorphisms of APC may confer a weaker risk for colorectal cancer. METHODS We sequenced the entire open reading frame of the APC gene and tested for two common MYH mutations in a population-based series of patients with colorectal cancer and 5 to 99 adenomas. Missense adenomatous polyposis coli alterations identified in this colorectal cancer multiple-polyp population were analyzed in a population-based series of patients with colorectal cancer and healthy control subjects. RESULTS Germline APC or mutY human homologue (MYH) alterations were identified in 16 of 39 colorectal cancer-multiple polyp patients. Four missense APC gene alterations (S130G, E1317Q, Dl822V, G2502S) were observed in 13 individuals and 3 additional patients carried presumed pathogenic (APC Y94X, biallelic MYH Y165C and heterozygous MYH G382D) mutations. When independently assessed in 971 patients with colorectal cancer and 954 healthy control subjects, none of the identified missense APC alterations conferred a significantly increased risk for colorectal cancer, odds ratio (95 percent confidence intervals): S130G=3.1 (0.29–32.25), E1317Q= 1.08 (0.59–2.74), G2502S= 1 (0.65–1.63), D1822V (heterozygous)=0.79 (0.64–0.98), D1822V (homozygous) =0.82 (0.63–1.27). CONCLUSIONS Germline missense APC alterations observed in 33 percent of patients with multiple colorectal neoplasms seemed to play a limited role in colorectal cancer risk when independently assessed by a population-based, case-control analysis. PMID:18612690

  9. Biomarkers for colitis-associated colorectal cancer.

    PubMed

    Chen, Ru; Lai, Lisa A; Brentnall, Teresa A; Pan, Sheng

    2016-09-21

    Patients with extensive ulcerative colitis (UC) of more than eight years duration have an increased risk of colorectal cancer. Molecular biomarkers for dysplasia and cancer could have a great clinical value in managing cancer risk in these UC patients. Using a wide range of molecular techniques - including cutting-edge OMICS technologies - recent studies have identified clinically relevant biomarker candidates from a variety of biosamples, including colonic biopsies, blood, stool, and urine. While the challenge remains to validate these candidate biomarkers in multi-center studies and with larger patient cohorts, it is certain that accurate biomarkers of colitis-associated neoplasia would improve clinical management of neoplastic risk in UC patients. This review highlights the ongoing avenues of research in biomarker development for colitis-associated colorectal cancer. PMID:27672285

  10. Biomarkers for colitis-associated colorectal cancer

    PubMed Central

    Chen, Ru; Lai, Lisa A; Brentnall, Teresa A; Pan, Sheng

    2016-01-01

    Patients with extensive ulcerative colitis (UC) of more than eight years duration have an increased risk of colorectal cancer. Molecular biomarkers for dysplasia and cancer could have a great clinical value in managing cancer risk in these UC patients. Using a wide range of molecular techniques - including cutting-edge OMICS technologies - recent studies have identified clinically relevant biomarker candidates from a variety of biosamples, including colonic biopsies, blood, stool, and urine. While the challenge remains to validate these candidate biomarkers in multi-center studies and with larger patient cohorts, it is certain that accurate biomarkers of colitis-associated neoplasia would improve clinical management of neoplastic risk in UC patients. This review highlights the ongoing avenues of research in biomarker development for colitis-associated colorectal cancer. PMID:27672285

  11. Biomarkers for colitis-associated colorectal cancer

    PubMed Central

    Chen, Ru; Lai, Lisa A; Brentnall, Teresa A; Pan, Sheng

    2016-01-01

    Patients with extensive ulcerative colitis (UC) of more than eight years duration have an increased risk of colorectal cancer. Molecular biomarkers for dysplasia and cancer could have a great clinical value in managing cancer risk in these UC patients. Using a wide range of molecular techniques - including cutting-edge OMICS technologies - recent studies have identified clinically relevant biomarker candidates from a variety of biosamples, including colonic biopsies, blood, stool, and urine. While the challenge remains to validate these candidate biomarkers in multi-center studies and with larger patient cohorts, it is certain that accurate biomarkers of colitis-associated neoplasia would improve clinical management of neoplastic risk in UC patients. This review highlights the ongoing avenues of research in biomarker development for colitis-associated colorectal cancer.

  12. Ramucirumab in metastatic colorectal cancer: evidence to date and place in therapy

    PubMed Central

    Verdaguer, Helena; Tabernero, Josep; Macarulla, Teresa

    2016-01-01

    Colorectal cancer is the third most frequent cancer worldwide. Overall survival rates have improved greatly over the last few years due, at least in part, to the addition of targeted therapies to standard of care chemotherapy. Angiogenesis plays an important role in colorectal cancer, and therapies directed against the vascular endothelial growth factor (VEGF) axis have contributed significantly to improving the outcome of patients with metastatic colorectal cancer. Over the past few years, several new targeted antiangiogenic agents have been approved for this patient population, confirming the value of inhibiting tumour angiogenesis. The most recent among them is ramucirumab, a fully humanized monoclonal antibody that targets the extracellular domain of VEGF receptor 2. It has proven valuable in multiple tumour types including colorectal cancer. Several phase I and II clinical trials showed a favourable toxicity profile and promising clinical antitumour efficacy in colorectal cancer patients. In the phase III RAISE clinical trial, the addition of ramucirumab to FOLFIRI-based chemotherapy resulted in an improvement of overall survival in patients with metastatic colorectal cancer who had been previously treated with bevacizumab, oxaliplatin and a fluoropyrimidine. On the basis of these results, ramucirumab was approved by the US Food and Drug Administration for this setting. We present an overview of the key preclinical and clinical studies in the development of ramucirumab in the context of metastatic colorectal cancer. PMID:27239240

  13. Ramucirumab in metastatic colorectal cancer: evidence to date and place in therapy.

    PubMed

    Verdaguer, Helena; Tabernero, Josep; Macarulla, Teresa

    2016-05-01

    Colorectal cancer is the third most frequent cancer worldwide. Overall survival rates have improved greatly over the last few years due, at least in part, to the addition of targeted therapies to standard of care chemotherapy. Angiogenesis plays an important role in colorectal cancer, and therapies directed against the vascular endothelial growth factor (VEGF) axis have contributed significantly to improving the outcome of patients with metastatic colorectal cancer. Over the past few years, several new targeted antiangiogenic agents have been approved for this patient population, confirming the value of inhibiting tumour angiogenesis. The most recent among them is ramucirumab, a fully humanized monoclonal antibody that targets the extracellular domain of VEGF receptor 2. It has proven valuable in multiple tumour types including colorectal cancer. Several phase I and II clinical trials showed a favourable toxicity profile and promising clinical antitumour efficacy in colorectal cancer patients. In the phase III RAISE clinical trial, the addition of ramucirumab to FOLFIRI-based chemotherapy resulted in an improvement of overall survival in patients with metastatic colorectal cancer who had been previously treated with bevacizumab, oxaliplatin and a fluoropyrimidine. On the basis of these results, ramucirumab was approved by the US Food and Drug Administration for this setting. We present an overview of the key preclinical and clinical studies in the development of ramucirumab in the context of metastatic colorectal cancer.

  14. Access to Cancer Services for Rural Colorectal Cancer Patients

    ERIC Educational Resources Information Center

    Baldwin, Laura-Mae; Cai, Yong; Larson, Eric H.; Dobie, Sharon A.; Wright, George E.; Goodman, David C.; Matthews, Barbara; Hart, L. Gary

    2008-01-01

    Context: Cancer care requires specialty surgical and medical resources that are less likely to be found in rural areas. Purpose: To examine the travel patterns and distances of rural and urban colorectal cancer (CRC) patients to 3 types of specialty cancer care services--surgery, medical oncology consultation, and radiation oncology consultation.…

  15. Comprehensive cancer control programs and coalitions: partnering to launch successful colorectal cancer screening initiatives.

    PubMed

    Seeff, Laura C; Major, Anne; Townsend, Julie S; Provost, Ellen; Redwood, Diana; Espey, David; Dwyer, Diane; Villanueva, Robert; Larsen, Leslie; Rowley, Kathryn; Leonard, Banning

    2010-12-01

    Colorectal cancer control has long been a focus area for Comprehensive Cancer Control programs and their coalitions, given the high burden of disease and the availability of effective screening interventions. Colorectal cancer control has been a growing priority at the national, state, territorial, tribal, and local level. This paper summarizes several national initiatives and features several Comprehensive Cancer Control Program colorectal cancer control successes.

  16. N-glycosylation of Colorectal Cancer Tissues

    PubMed Central

    Balog, Crina I. A.; Stavenhagen, Kathrin; Fung, Wesley L. J.; Koeleman, Carolien A.; McDonnell, Liam A.; Verhoeven, Aswin; Mesker, Wilma E.; Tollenaar, Rob A. E. M.; Deelder, André M.; Wuhrer, Manfred

    2012-01-01

    Colorectal cancer is the third most common cancer worldwide with an annual incidence of ∼1 million cases and an annual mortality rate of ∼655,000 individuals. There is an urgent need for identifying novel targets to develop more sensitive, reliable, and specific tests for early stage detection of colon cancer. Post-translational modifications are known to play an important role in cancer progression and immune surveillance of tumors. In the present study, we compared the N-glycan profiles from 13 colorectal cancer tumor tissues and corresponding control colon tissues. The N-glycans were enzymatically released, purified, and labeled with 2-aminobenzoic acid. Aliquots were profiled by hydrophilic interaction liquid chromatography (HILIC-HPLC) with fluorescence detection and by negative mode MALDI-TOF-MS. Using partial least squares discriminant analysis to investigate the N-glycosylation changes in colorectal cancer, an excellent separation and prediction ability were observed for both HILIC-HPLC and MALDI-TOF-MS data. For structure elucidation, information from positive mode ESI-ion trap-MS/MS and negative mode MALDI-TOF/TOF-MS was combined. Among the features with a high separation power, structures containing a bisecting GlcNAc were found to be decreased in the tumor, whereas sulfated glycans, paucimannosidic glycans, and glycans containing a sialylated Lewis type epitope were shown to be increased in tumor tissues. In addition, core-fucosylated high mannose N-glycans were detected in tumor samples. In conclusion, the combination of HILIC and MALDI-TOF-MS profiling of N-glycans with multivariate statistical analysis demonstrated its potential for identifying N-glycosylation changes in colorectal cancer tissues and provided new leads that might be used as candidate biomarkers. PMID:22573871

  17. BRAF Mutation in Colorectal Cancer: An Update

    PubMed Central

    Barras, David

    2015-01-01

    Colorectal cancer (CRC) is still one of the deadliest cancer-related diseases. About 10% of CRC patients are characterized by a mutation in the B-Raf proto-oncogene serine/threonine kinase (BRAF) gene resulting in a valine-to-glutamate change at the residue 600 (V600E). This mutation is also present in more than 60% of melanoma patients. BRAF inhibitors were developed and found to improve patient survival; however, most patients at the end of the track ultimately develop resistance to these inhibitors. Melanoma patients benefit from the combination of BRAF inhibitors with mitogen/extracellular signal-regulated kinase (MEK) inhibitors, among others. Unfortunately, colorectal patients do not respond much efficiently, which suggests different resistance mechanisms between the two cancer types. This review aims at shedding light on recent discoveries that improve our understanding of the BRAF mutation biology in CRC. PMID:26396549

  18. Therapeutic strategy in unresectable metastatic colorectal cancer

    PubMed Central

    Tournigand, Christophe; André, Thierry; de Gramont, Aimery

    2012-01-01

    While surgery is the cornerstone treatment for early-stage colorectal cancer, chemotherapy is the first treatment option for metastatic disease when tumor lesions are frequently not fully resectable at presentation. Mortality from colon cancer has decreased over the past 30 years, but there is still a huge heterogeneity in survival rates that can be mainly explained by patient and tumor characteristics, host response factors, and treatment modalities. The management of unresectable metastatic colorectal cancer is a global treatment strategy, which applies several lines of therapy, salvage surgery, maintenance, and treatment-free intervals. The individualization of cancer treatment is based on the evaluation of prognostic factors for survival (serum lactate dehydrogenase level, performance status), and predictive factors for treatment efficacy [Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation status]. The available treatment modalities for metastatic colorectal cancer are chemotherapy (fluoropyrimidine, oxaliplatin, irinotecan), anti-angiogenic agents (e.g. bevacizumab), and anti-epidermal growth factor agents (cetuximab, panitumumab). The increasing number of active compounds dictates the strategy of trials evaluating these treatments either in combination or sequentially. Alternative outcomes that can be measured earlier than overall survival are needed to shorten the duration and reduce the size and cost of clinical trials. PMID:22423266

  19. Gut microbiota and colorectal cancer.

    PubMed

    Yamamoto, Mayuko; Matsumoto, Satoshi

    2016-01-01

    The mucosal immune system is unique to the gastrointestinal mucosa, in which a large number of immune cells are located and exert multiple functions. Meanwhile, ~100 trillion microorganisms are thought to co-inhabit in the gastrointestinal tract. Furthermore, immune cells and gut microbiota have a mutual influence and the maintenance of this symbiotic relationship results in gut homeostasis. A recent study suggested that a disturbance of gut microbiota-so called "dysbiosis"-is related to various diseases, such as inflammatory bowel disease (IBD) and colitis-associated cancer (CAC). In this review, we discuss the relationship between gut microbiota and the mucosal immune system with regard to the development of IBD and CAC. In addition, we elucidate the possibility of probiotics in treatment against these diseases. PMID:27350830

  20. Identification and characterization of RET fusions in advanced colorectal cancer

    PubMed Central

    Garrett, Christopher R.; Seery, Tara; Sanford, Eric M.; Balasubramanian, Sohail; Ross, Jeffrey S.; Stephens, Philip J.; Miller, Vincent A.; Ali, Siraj M.; Chiu, Vi K.

    2015-01-01

    There is an unmet clinical need for molecularly directed therapies available for metastatic colorectal cancer. Comprehensive genomic profiling has the potential to identify actionable genomic alterations in colorectal cancer. Through comprehensive genomic profiling we prospectively identified 6 RET fusion kinases, including two novel fusions of CCDC6-RET and NCOA4-RET, in metastatic colorectal cancer (CRC) patients. RET fusion kinases represent a novel class of oncogenic driver in CRC and occurred at a 0.2% frequency without concurrent driver mutations, including KRAS, NRAS, BRAF, PIK3CA or other fusion tyrosine kinases. Multiple RET kinase inhibitors were cytotoxic to RET fusion kinase positive cancer cells and not RET fusion kinase negative CRC cells. The presence of a RET fusion kinase may identify a subset of metastatic CRC patients with a high response rate to RET kinase inhibition. This is the first characterization of RET fusions in CRC patients and highlights the therapeutic significance of prospective comprehensive genomic profiling in advanced CRC. PMID:26078337

  1. Identification and characterization of RET fusions in advanced colorectal cancer.

    PubMed

    Le Rolle, Anne-France; Klempner, Samuel J; Garrett, Christopher R; Seery, Tara; Sanford, Eric M; Balasubramanian, Sohail; Ross, Jeffrey S; Stephens, Philip J; Miller, Vincent A; Ali, Siraj M; Chiu, Vi K

    2015-10-01

    There is an unmet clinical need for molecularly directed therapies available for metastatic colorectal cancer. Comprehensive genomic profiling has the potential to identify actionable genomic alterations in colorectal cancer. Through comprehensive genomic profiling we prospectively identified 6 RET fusion kinases, including two novel fusions of CCDC6-RET and NCOA4-RET, in metastatic colorectal cancer (CRC) patients. RET fusion kinases represent a novel class of oncogenic driver in CRC and occurred at a 0.2% frequency without concurrent driver mutations, including KRAS, NRAS, BRAF, PIK3CA or other fusion tyrosine kinases. Multiple RET kinase inhibitors were cytotoxic to RET fusion kinase positive cancer cells and not RET fusion kinase negative CRC cells. The presence of a RET fusion kinase may identify a subset of metastatic CRC patients with a high response rate to RET kinase inhibition. This is the first characterization of RET fusions in CRC patients and highlights the therapeutic significance of prospective comprehensive genomic profiling in advanced CRC. PMID:26078337

  2. Circulating Non-coding RNA as Biomarkers in Colorectal Cancer.

    PubMed

    Ferracin, Manuela; Lupini, Laura; Mangolini, Alessandra; Negrini, Massimo

    2016-01-01

    Recent studies suggested that colorectal cancer influences the types and quantity of nucleic acids - especially microRNAs - detected in the bloodstream. Concentration of circulating (cell-free) microRNAs, and possibly of other non-coding RNAs, could therefore serve as valuable colorectal cancer biomarker and could deliver insight into the disease process. This chapter addresses the recent discoveries on circulating microRNA and long non-coding RNA as diagnostic or prognostic biomarkers in colorectal cancer. PMID:27573900

  3. Colorectal cancer risk in hamartomatous polyposis syndromes

    PubMed Central

    Campos, Fábio Guilherme; Figueiredo, Marleny Novaes; Martinez, Carlos Augusto Real

    2015-01-01

    Colorectal cancer (CRC) is a major cause of morbidity and mortality around the world, and approximately 5% of them develop in a context of inherited mutations leading to some form of familial colon cancer syndromes. Recognition and characterization of these patients have contributed to elucidate the genetic basis of CRC. Polyposis Syndromes may be categorized by the predominant histological structure found within the polyps. The aim of the present paper is to review the most important clinical features of the Hamartomatous Polyposis Syndromes, a rare group of genetic disorders formed by the peutz-Jeghers syndrome, juvenil polyposis syndrome and PTEN Hamartoma Tumor Syndrome (Bannayan-Riley-Ruvalacaba and Cowden Syndromes). A literature search was performed in order to retrieve the most recent and important papers (articles, reviews, clinical cases and clinical guidelines) regarding the studied subject. We searched for terms such as “hamartomatous polyposis syndromes”, “Peutz-Jeghers syndrome”, “juvenile polyposis syndrome”, “juvenile polyp”, and “PTEN hamartoma tumour syndrome” (Cowden syndrome, Bananyan-Riley-Ruvalcaba). The present article reports the wide spectrum of disease severity and extraintestinal manifestations, with a special focus on their potential to develop colorectal and other neoplasia. In the literature, the reported colorectal cancer risk for Juvenile Polyposis, Peutz-Jeghers and PTEN Hamartoma Tumor Syndromes are 39%-68%, 39%-57% and 18%, respectively. A review regarding cancer surveillance recommendations is also presented. PMID:25848489

  4. Colorectal cancer risk in hamartomatous polyposis syndromes.

    PubMed

    Campos, Fábio Guilherme; Figueiredo, Marleny Novaes; Martinez, Carlos Augusto Real

    2015-03-27

    Colorectal cancer (CRC) is a major cause of morbidity and mortality around the world, and approximately 5% of them develop in a context of inherited mutations leading to some form of familial colon cancer syndromes. Recognition and characterization of these patients have contributed to elucidate the genetic basis of CRC. Polyposis Syndromes may be categorized by the predominant histological structure found within the polyps. The aim of the present paper is to review the most important clinical features of the Hamartomatous Polyposis Syndromes, a rare group of genetic disorders formed by the peutz-Jeghers syndrome, juvenil polyposis syndrome and PTEN Hamartoma Tumor Syndrome (Bannayan-Riley-Ruvalacaba and Cowden Syndromes). A literature search was performed in order to retrieve the most recent and important papers (articles, reviews, clinical cases and clinical guidelines) regarding the studied subject. We searched for terms such as "hamartomatous polyposis syndromes", "Peutz-Jeghers syndrome", "juvenile polyposis syndrome", "juvenile polyp", and "PTEN hamartoma tumour syndrome" (Cowden syndrome, Bananyan-Riley-Ruvalcaba). The present article reports the wide spectrum of disease severity and extraintestinal manifestations, with a special focus on their potential to develop colorectal and other neoplasia. In the literature, the reported colorectal cancer risk for Juvenile Polyposis, Peutz-Jeghers and PTEN Hamartoma Tumor Syndromes are 39%-68%, 39%-57% and 18%, respectively. A review regarding cancer surveillance recommendations is also presented.

  5. Treatment of colorectal cancer in the elderly

    PubMed Central

    Millan, Monica; Merino, Sandra; Caro, Aleidis; Feliu, Francesc; Escuder, Jordi; Francesch, Tani

    2015-01-01

    Colorectal cancer has a high incidence, and approximately 60% of colorectal cancer patients are older than 70, with this incidence likely increasing in the near future. Elderly patients (> 70-75 years of age) are a very heterogeneous group, ranging from the very fit to the very frail. Traditionally, these patients have often been under-treated and recruited less frequently to clinical trials than younger patients, and thus are under-represented in publications about cancer treatment. Recent studies suggest that fit elderly patients can be treated in the same way as their younger counterparts, but the treatment of frail patients with comorbidities is still a matter of controversy. Many factors should be taken into account, including fitness for treatment, the wishes of the patient and family, and quality of life. This review will focus on the existing evidence for surgical, oncologic, and palliative treatment in patients over 70 years old with colorectal cancer. Careful patient assessment is necessary in order to individualize treatment approach, and this should rely on a multidisciplinary process. More well-designed controlled trials are needed in this patient population. PMID:26483875

  6. Diet and supplements and their impact on colorectal cancer

    PubMed Central

    Pericleous, Marinos; Mandair, Dalvinder

    2013-01-01

    Background Colorectal cancer is the third commonest cancer and the third leading cause of cancer death among men and women. It has been proposed that dietary factors are responsible for 70-90% of colorectal cancer and diet optimization may prevent most cases. Aim To evaluate the role of dietary components and supplements in colorectal cancer. Methods Bibliographical searches were performed in Pubmed for the terms “diet and colorectal cancer”, “diet and colon cancer”, “diet and rectal cancer”, “nutrition and colorectal cancer”, “probiotics and colorectal cancer”, “prebiotics and colorectal cancer”, “alcohol and cancer” and “colorectal cancer epidemiology”. Results Consumption of processed or red meat, especially when cooked at high temperatures may be associated with increased risk of colorectal cancer. The evidence for dietary fibre is unclear but foods that contain high amounts of fibre are usually rich in polyphenols which have been shown to alter molecular processes that can encourage colorectal carcinogenesis. Meta-analyses provide evidence on the benefits of circulating, diet-derived and supplemented, vitamin D and Calcium. We also found that diets rich in Folate may prevent colorectal carcinoma. The evidence on dietary micronutrients such as Zinc and Selenium in association with colorectal cancer is not conclusive. It has been suggested that there may be a direct association between alcohol intake and colorectal cancer. In vitro and in vivo studies have highlighted a possible protective role of prebiotics and probiotics. Conclusions The lack of randomized trials and the presence of confounding factors including smoking, physical activity, obesity and diabetes may often yield inconclusive results. Carefully designed randomized trials are recommended. PMID:24294513

  7. Serum amino acid profiles and their alterations in colorectal cancer.

    PubMed

    Leichtle, Alexander Benedikt; Nuoffer, Jean-Marc; Ceglarek, Uta; Kase, Julia; Conrad, Tim; Witzigmann, Helmut; Thiery, Joachim; Fiedler, Georg Martin

    2012-08-01

    Mass spectrometry-based serum metabolic profiling is a promising tool to analyse complex cancer associated metabolic alterations, which may broaden our pathophysiological understanding of the disease and may function as a source of new cancer-associated biomarkers. Highly standardized serum samples of patients suffering from colon cancer (n = 59) and controls (n = 58) were collected at the University Hospital Leipzig. We based our investigations on amino acid screening profiles using electrospray tandem-mass spectrometry. Metabolic profiles were evaluated using the Analyst 1.4.2 software. General, comparative and equivalence statistics were performed by R 2.12.2. 11 out of 26 serum amino acid concentrations were significantly different between colorectal cancer patients and healthy controls. We found a model including CEA, glycine, and tyrosine as best discriminating and superior to CEA alone with an AUROC of 0.878 (95% CI 0.815-0.941). Our serum metabolic profiling in colon cancer revealed multiple significant disease-associated alterations in the amino acid profile with promising diagnostic power. Further large-scale studies are necessary to elucidate the potential of our model also to discriminate between cancer and potential differential diagnoses. In conclusion, serum glycine and tyrosine in combination with CEA are superior to CEA for the discrimination between colorectal cancer patients and controls.

  8. Optimising colorectal cancer screening acceptance: a review.

    PubMed

    Senore, Carlo; Inadomi, John; Segnan, Nereo; Bellisario, Cristina; Hassan, Cesare

    2015-07-01

    The study aims to review available evidence concerning effective interventions to increase colorectal cancer (CRC) screening acceptance. We performed a literature search of randomised trials designed to increase individuals' use of CRC screening on PubMed, Embase, Cochrane Database of Systematic Reviews and Database of Abstracts of Reviews of Effects. Small (≤ 100 subjects per arm) studies and those reporting results of interventions implemented before publication of the large faecal occult blood test trials were excluded. Interventions were categorised following the Continuum of Cancer Care and the PRECEDE-PROCEED models and studies were grouped by screening model (opportunistic vs organised). Multifactor interventions targeting multiple levels of care and considering factors outside the individual clinician control, represent the most effective strategy to enhance CRC screening acceptance. Removing financial barriers, implementing methods allowing a systematic contact of the whole target population, using personal invitation letters, preferably signed by the reference care provider, and reminders mailed to all non-attendees are highly effective in enhancing CRC screening acceptance. Physician reminders may support the diffusion of screening, but they can be effective only for individuals who have access to and make use of healthcare services. Educational interventions for patients and providers are effective, but the implementation of organisational measures may be necessary to favour their impact. Available evidence indicates that organised programmes allow to achieve an extensive coverage and to enhance equity of access, while maximising the health impact of screening. They provide at the same time an infrastructure allowing to achieve a more favourable cost-effectiveness profile of potentially effective strategies, which would not be sustainable in opportunistic settings. PMID:26059765

  9. What's new in hereditary colorectal cancer?

    PubMed

    Jass, Jeremy R

    2005-11-01

    Precancerous polyposes other than classic familial adenomatous polyposis and the condition hereditary nonpolyposis colorectal cancer, or Lynch syndrome, continue to present major diagnostic challenges for the anatomic pathologist. This editorial highlights the practical significance of novel insights and clinical guidelines in the recent literature, as well as in 4 contributions to this edition of the Archives of Pathology & Laboratory Medicine. The first section will address attenuated familial adenomatous polyposis and a newly recognized type of autosomal-recessive adenomatous polyposis associated with the DNA repair gene MYH. The remainder of the editorial discusses the role of the revised Bethesda guidelines in the diagnosis of hereditary nonpolyposis colorectal cancer and concludes with the recently identified serrated pathway syndrome.

  10. Endoluminal Therapy in Colorectal Cancer.

    PubMed

    Kelley, Katherine A; Tsikitis, V Liana

    2016-09-01

    Appropriate endoscopic resection for colorectal polyps can present a challenge to endoscopists, as these lesions may harbor malignancy. With recent advances in endoscopy, however, we are now entering an exciting frontier of endoscopic therapy for gastrointestinal lesions. These techniques include endoluminal mucosal resection and endoscopic submucosal dissection, which may be utilized on several colonic lesions. This article will discuss these principle endoscopic techniques, their outcomes, and briefly highlight their influence on endoscopic interventions, including transanal endoscopic microsurgery and natural orifice transluminal endoscopic surgery. PMID:27582646

  11. Colorectal Cancer with Uncommon Metastatic Spread

    PubMed Central

    Dellavedova, Luca; Calcagno, Anna; Roncoroni, Lucia; Maffioli, Lorenzo Stefano

    2015-01-01

    The prevalence of bone metastases from colorectal cancer (CRC) is quite low and the presence of isolated osseous metastases at the time of diagnosis or the onset of bone metastases without other organ involvement during follow-up is even lower. Here, we present an interesting case of diffuse skeletal metastases from CRC in which both the atypical presentation of the metastatic spread and the presence of infective comorbidities created some troubles in getting the final diagnosis. PMID:26420997

  12. Circulating tumor cells in colorectal cancer patients.

    PubMed

    Torino, Francesco; Bonmassar, Enzo; Bonmassar, Laura; De Vecchis, Liana; Barnabei, Agnese; Zuppi, Cecilia; Capoluongo, Ettore; Aquino, Angelo

    2013-11-01

    The availability of sensitive methods has allowed the detailed study of circulating tumor cells only recently. Evolving evidence support the prognostic and predictive role of these cells in patients affected by several solid tumors, including colorectal cancer. Ongoing studies are aimed at confirming that the molecular characterization of circulating tumor cells in peripheral blood and in bone marrow of patients is a powerful tool to improve the patient risk-stratification, to monitor activity of the drugs, to develop more appropriate targeted therapies and tailored treatments. In parallel, results from these correlative studies promise to gain a better biological understanding of the metastatic process. The clinical utility of the detection of circulating tumor cells in patients affected by colorectal cancer is still hampered by a number of specific hurdles. Improvement in sensitivity and specificity of the available methods of detection, standardization of these methods and functional characterization of circulating tumor cells in well designed and statistically well powered studies are the key steps to reach these ambitious objectives in colorectal cancer patients as well.

  13. Aflibercept in the Treatment of Metastatic Colorectal Cancer

    PubMed Central

    Wang, Tzu-Fei; Lockhart, Albert Craig

    2012-01-01

    Colorectal cancer is the third most common cancer in the US. In recent decades, an improved understanding of the role of the angiogenesis pathway in colorectal cancer has led to advancements in treatment. Bevacizumab has been shown to improve the progression-free survival and overall survival when combined with cytotoxic chemotherapy in patients with metastatic colorectal cancer, and at present is the only antiangiogenesis agent approved for the treatment of this cancer. Aflibercept is a novel angiogenesis-targeting agent, and has demonstrated efficacy in treating metastatic colorectal cancer in a recent randomized Phase III trial. Here we review the role of angiogenesis in the tumorigenesis of colorectal cancer, strategies for targeting angiogenesis, and the clinical development of aflibercept. PMID:22253552

  14. [Cyclooxygenase 2 inhibitors and colorectal cancer].

    PubMed

    Bernardeau-Mozer, Marianne; Chaussade, Stanislas

    2004-05-01

    Cyclooxygenase-2 (Cox2) is an inductible isoenzyme of cyclooxygenase undetectable in normal colonic mucosa and overexpressed in 80% colonic tumor. Several works in vitro and in vivo showed that Cox2 plays a key role in the multistep process of colorectal tumorigenesis such apoptosis inhibition of cellular proliferation and angiogenesis induction. So that Cox2 represent a potential molecular target in colorectal management and specific Cox2 inhibitors may be useful as chemopreventive as well as therapeutic agent in humans. In animals study Cox2 inhibitors was shown to be effective and in humans Cox2 inhibitors are approved by the Food and Drug Administration as an adjunct to endoscopic surveillance and surgery in patients with Familial Adenomatous Polyposis (FAP). The purpose of this article is to review the relationship between Cox2/Cox2 inhibitors and differents signaling pathways of colorectal carcinogenesis and to precise their possible molecular mechanisms of action. This work although review clinicals data of their efficacy as chemopreventive agent as well as therapeutic in the differents group at risk for colorectal cancer. PMID:15239336

  15. Colorectal Cancer Risk Assessment Tool

    MedlinePlus

    ... Rectal Cancer Home Page Colon and Rectal Cancer: Prevention, Genetics, Causes Tests to ... corresponding to answers “medications that do not contain aspirin unknown" (page 4 of 7). Things to know ...

  16. Variation in the association between colorectal cancer susceptibility loci and colorectal polyps by polyp type.

    PubMed

    Burnett-Hartman, Andrea N; Newcomb, Polly A; Hutter, Carolyn M; Peters, Ulrike; Passarelli, Michael N; Schwartz, Malaika R; Upton, Melissa P; Zhu, Lee-Ching; Potter, John D; Makar, Karen W

    2014-07-15

    We conducted a case-control study of the association between subsets of colorectal polyps, including adenomas and serrated polyps, and single-nucleotide polymorphisms (SNPs) related to colorectal cancer through prior genome-wide association studies (GWAS). Participants were enrollees in the Group Health Cooperative (Seattle, Washington) aged 24-79 years who received a colonoscopy from 1998 to 2007, donated a buccal or blood sample, and completed a structured questionnaire. We performed genotyping of 13 colorectal cancer susceptibility SNPs. Polytomous logistic regression models were used to estimate odds ratios and 95% confidence intervals for associations between polyps and the colorectal cancer risk allele for each SNP under a log-additive model. Analyses included 781 controls, 489 cases with adenoma, 401 cases with serrated polyps, and 188 cases with both polyp types. The following SNPs were associated with advanced adenomas: rs10936599, rs10795668, rs16892766, and rs9929218 (P < 0.05). For nonadvanced adenomas and for serrated polyps overall, only rs961253 was statistically significant (P < 0.05). These associations were in the same directions as those in prior colorectal cancer GWAS. No SNP was significantly associated with hyperplastic polyps, and only rs6983267 was significantly associated with sessile serrated polyps, but this association was opposite of that found in colorectal cancer GWAS. Our results suggest that the association between colorectal cancer susceptibility SNPs and colorectal polyps varies by polyp type.

  17. Associations between NBS1 Polymorphisms and Colorectal Cancer in Chinese Population.

    PubMed

    Li, Jing-Tao; Zhong, Bao-Yuan; Xu, Hui-Hui; Qiao, Sheng-Yan; Wang, Gui; Huang, Jing; Fan, Hui-Zhen; Zhao, Hong-Chuan

    2015-01-01

    As the central protein of the double strand breaks (DSB)-induced DNA repair pathway, NBS1 participates in detecting the DSBs and plays an essential role in maintaining genomic stability. Single nucleotide polymorphisms (SNPs) in NBS1 gene were commonly tested that associated with the susceptibility to multiple cancers, but the results remained controversial. Thus, we conducted two independent hospital-based case-control studies comprising 1,072 colorectal cancer patients and 1,263 controls to evaluate the association between four NBS1 SNPs and colorectal cancer risk. The result showed that rs2735383C/G polymorphism in the 3'-untranslated region (UTR) of NBS1 was significantly associated with risk of colorectal cancer using logistic regression (P<10(-4)). Furthermore, we observed that rs2735383CC genotype was associated with substantially increased risk of colorectal cancer (odds ratio=1.55, 95% confidence interval=1.27-1.94), compared with the rs2735383GC+GG genotypes. Further functional experiments demonstrated that the rs2735383C allele in the NBS1 disrupted the binding affinity of has-miR-509-5p to the NBS1 3'-UTR in colorectal cancer cells, affecting the NBS1 transcriptional activity and expression level. In conclusion, current evidence suggests that the rs2735383C/G polymorphism might contribute to the risk for colorectal cancer.

  18. Immune cell interplay in colorectal cancer prognosis

    PubMed Central

    Norton, Samuel E; Ward-Hartstonge, Kirsten A; Taylor, Edward S; Kemp, Roslyn A

    2015-01-01

    The immune response to colorectal cancer has proven to be a reliable measure of patient outcome in several studies. However, the complexity of the immune response in this disease is not well understood, particularly the interactions between tumour-associated cells and cells of the innate and adaptive immune system. This review will discuss the relationship between cancer associated fibroblasts and macrophages, as well as between macrophages and T cells, and demonstrate how each population may support or prevent tumour growth in a different immune environment. PMID:26483876

  19. Aspirin Metabolomics in Colorectal Cancer Chemoprevention | Division of Cancer Prevention

    Cancer.gov

    DESCRIPTION (provided by applicant): Substantial evidence supports the effectiveness of aspirin for cancer chemoprevention in addition to its well-established role in cardiovascular protection. In recent meta-analyses of randomized controlled trials in humans, daily aspirin use reduced incidence, metastasis and mortality from several common types of cancer, especially colorectal cancer. The mechanism(s) by which aspirin exerts an anticancer benefit is uncertain;numerous effects have been described involving both cyclooxygenase-dependent and -independent pathways. |

  20. Perceived religiousness is protective for colorectal cancer: data from the Melbourne Colorectal Cancer Study.

    PubMed Central

    Kune, G A; Kune, S; Watson, L F

    1993-01-01

    The perceived or self-reported degree of 'religiousness' was obtained by interview from 715 colorectal cancer patients and 727 age/sex matched community controls, as part of a large, comprehensive population-based study of colorectal cancer incidence, aetiology and survival (The Melbourne Colorectal Cancer Study) conducted in Melbourne, Australia. Self-reported or perceived 'religiousness', as defined in the study, was a statistically significant protective factor [relative risk (RR) = 0.70, 95% confidence interval (CI) = 0.6-0.9, P = 0.002]. This statistically significant protection remained after the previously determined major risk factors found in the study, namely a family history of colorectal cancer, dietary risk factors, beer consumption, number of children and age at birth of the first child, were statistically corrected for (P = 0.004). There was no association between Dukes' staging of the cancer and perceived degree of 'religiousness' (P = 0.42). Although self-reported or perceived 'religiousness' was associated with a median survival time of 62 months compared with 52 months in those self-reporting as being 'non-religious', this difference was not statistically significant (P = 0.64). PMID:8258800

  1. TNIK inhibition abrogates colorectal cancer stemness

    PubMed Central

    Masuda, Mari; Uno, Yuko; Ohbayashi, Naomi; Ohata, Hirokazu; Mimata, Ayako; Kukimoto-Niino, Mutsuko; Moriyama, Hideki; Kashimoto, Shigeki; Inoue, Tomoko; Goto, Naoko; Okamoto, Koji; Shirouzu, Mikako; Sawa, Masaaki; Yamada, Tesshi

    2016-01-01

    Canonical Wnt/β-catenin signalling is essential for maintaining intestinal stem cells, and its constitutive activation has been implicated in colorectal carcinogenesis. We and others have previously identified Traf2- and Nck-interacting kinase (TNIK) as an essential regulatory component of the T-cell factor-4 and β-catenin transcriptional complex. Consistent with this, Tnik-deficient mice are resistant to azoxymethane-induced colon tumorigenesis, and Tnik−/−/Apcmin/+ mutant mice develop significantly fewer intestinal tumours. Here we report the first orally available small-molecule TNIK inhibitor, NCB-0846, having anti-Wnt activity. X-ray co-crystal structure analysis reveals that NCB-0846 binds to TNIK in an inactive conformation, and this binding mode seems to be essential for Wnt inhibition. NCB-0846 suppresses Wnt-driven intestinal tumorigenesis in Apcmin/+ mice and the sphere- and tumour-forming activities of colorectal cancer cells. TNIK is required for the tumour-initiating function of colorectal cancer stem cells. Its inhibition is a promising therapeutic approach. PMID:27562646

  2. TNIK inhibition abrogates colorectal cancer stemness.

    PubMed

    Masuda, Mari; Uno, Yuko; Ohbayashi, Naomi; Ohata, Hirokazu; Mimata, Ayako; Kukimoto-Niino, Mutsuko; Moriyama, Hideki; Kashimoto, Shigeki; Inoue, Tomoko; Goto, Naoko; Okamoto, Koji; Shirouzu, Mikako; Sawa, Masaaki; Yamada, Tesshi

    2016-01-01

    Canonical Wnt/β-catenin signalling is essential for maintaining intestinal stem cells, and its constitutive activation has been implicated in colorectal carcinogenesis. We and others have previously identified Traf2- and Nck-interacting kinase (TNIK) as an essential regulatory component of the T-cell factor-4 and β-catenin transcriptional complex. Consistent with this, Tnik-deficient mice are resistant to azoxymethane-induced colon tumorigenesis, and Tnik(-/-)/Apc(min/+) mutant mice develop significantly fewer intestinal tumours. Here we report the first orally available small-molecule TNIK inhibitor, NCB-0846, having anti-Wnt activity. X-ray co-crystal structure analysis reveals that NCB-0846 binds to TNIK in an inactive conformation, and this binding mode seems to be essential for Wnt inhibition. NCB-0846 suppresses Wnt-driven intestinal tumorigenesis in Apc(min/+) mice and the sphere- and tumour-forming activities of colorectal cancer cells. TNIK is required for the tumour-initiating function of colorectal cancer stem cells. Its inhibition is a promising therapeutic approach. PMID:27562646

  3. GREM 1 and POLE variants in hereditary colorectal cancer syndromes

    PubMed Central

    Eiengård, Frida; Lundstam, Ulf; Zagoras, Theofanis; Nilsson, Staffan; Edsjö, Anders; Pedersen, Jan; Svensson, Janhenry; Skullman, Stefan; Karlsson, B. Göran; Björk, Jan; Nordling, Margareta

    2015-01-01

    Hereditary factors are thought to play a role in at least one third of patients with colorectal cancer (CRC) but only a limited proportion of these have mutations in known high‐penetrant genes. In a relatively large part of patients with a few or multiple colorectal polyps the underlying genetic cause of the disease is still unknown. Using exome sequencing in combination with linkage analyses together with detection of copy‐number variations (CNV), we have identified a duplication in the regulatory region of the GREM1 gene in a family with an attenuated/atypical polyposis syndrome. In addition, 107 patients with colorectal cancer and/or polyposis were analyzed for mutations in the candidate genes identified. We also performed screening of the exonuclease domain of the POLE gene in a subset of these patients. The duplication of 16 kb in the regulatory region of GREM1 was found to be disease‐causing in the family. Functional analyses revealed a higher expression of the GREM1 gene in colorectal tissue in duplication carriers. Screening of the exonuclease domain of POLE in additional CRC patients identified a probable causative novel variant c.1274A>G, p.Lys425Arg. In conclusion a high penetrant duplication in the regulatory region of GREM1, predisposing to CRC, was identified in a family with attenuated/atypical polyposis. A POLE variant was identified in a patient with early onset CRC and a microsatellite stable (MSS) tumor. Mutations leading to increased expression of genes can constitute disease‐causing mutations in hereditary CRC syndromes. © 2015 The Authors. Genes, Chromosomes & Cancer Published by Wiley Periodicals, Inc. PMID:26493165

  4. NIH study finds sigmoidoscopy reduces colorectal cancer rates

    Cancer.gov

    Study finds that flexible sigmoidoscopy is effective in reducing the rates of new cases and deaths due to colorectal cancer. Researchers found that overall colorectal cancer mortality was reduced by 26 percent and incidence was reduced by 21 percent as a

  5. Genetic Heterogeneity in Colorectal Cancer and its Clinical Implications.

    PubMed

    Barranha, Rui; Costa, José Luís; Carneiro, Fátima; Machado, José Carlos

    2015-01-01

    Despite the recent advances in the development of complementary diagnostic exams and modern targeted therapies, colorectal cancer remains a major cause of morbidity and mortality worldwide. In this context, a lot of research has been conducted in the last years to find new markers of poor prognosis. The existence of a complex tumour architecture formed by multiple subclones genetically heterogeneous has been increasingly considered in recent studies as an element of particular importance. This feature seems to influence factors as relevant as the representativeness of tumour biopsies for genetic diagnosis and the efficacy of targeted therapies.There is growing evidence suggesting a relation between genetic heterogeneity and the patientsâ prognosis. The widespread use of next-generation sequencing techniques will allow a better understanding of the true degree of genetic heterogeneity in colorectal tumours, its causes and impact on the course of the disease. In this review we intend to analyse the recent findings related to the genetic heterogeneity of colorectal cancer, as well as its major clinical implications.

  6. Occupation-related risks for colorectal cancer

    SciTech Connect

    Spiegelman, D.; Wegman, D.H.

    1985-11-01

    Several population data bases were used to generate hypotheses about associations between colorectal cancer and workplace exposures. The Third National Cancer Survey interview sample was used to select 343 male and 208 female cases and 626 male and 1,235 female cancer controls. Potential work exposures were assigned with the use of data from the National Institute for Occupational Safety and Health National Occupational Hazard Survey. Dietary factors were modeled from the National Health and Nutrition Examination Survey data. Work-related stress was considered with the use of a model based on the U.S. Department of Labor's Quality of Employment Survey. Other risk factors included age, race, ponderosity, and menopausal status. Logistic analysis yielded hypotheses for colon cancer risk in males with potentially high exposure to solvents, abrasives, and fuel oil and in those in jobs with high demand and low control (high stress). Hypotheses emerged for females with potentially high exposure to dyes, solvents, and grinding wheel dust.

  7. Genetic pathways in colorectal and other cancers.

    PubMed

    Ilyas, M; Straub, J; Tomlinson, I P; Bodmer, W F

    1999-12-01

    Cells from cancers show aberrant behaviour such as unrestrained growth, invasion into adjacent tissue and metastasis. All these features of cancer cell behaviour can be explained in terms of genetic changes and the functional impact of these changes. In this review, colorectal cancer (CRC) is examined as a classical example of multistep carcinogenesis. First there is an overview which shows that cancers develop by a process of somatic evolution. This gives rise to preferred genetic pathways of tumorigenesis. The factors which may influence the development and ultimate choice of genetic pathways are then examined. Next, CRC is studied as a specific disease and the putative genetic pathways are described. The mutations that comprise these pathways and the possible functional sequelae of these are explored. The review concludes with a look at those avenues which may further elucidate the natural history of CRC and lead to improved therapy.

  8. Genetic pathways in colorectal and other cancers.

    PubMed

    Ilyas, M; Straub, J; Tomlinson, I P; Bodmer, W F

    1999-03-01

    Cells from cancers show aberrant behaviour such as unrestrained growth, invasion into adjacent tissue and metastasis. All these features of cancer cell behaviour can be explained in terms of genetic changes and the functional impact of these changes. In this review, colorectal cancer (CRC) is examined as a classical example of multistep carcinogenesis. First there is an overview which shows that cancers develop by a process of somatic evolution. This gives rise to preferred genetic pathways of tumorigenesis. The factors which may influence the development and ultimate choice of genetic pathways are then examined. Next, CRC is studied as a specific disease and the putative genetic pathways are described. The mutations that comprise these pathways and the possible functional sequelae of these are explored. The review concludes with a look at those avenues which may further elucidate the natural history of CRC and lead to improved therapy.

  9. Virtual colonoscopy in stenosing colorectal cancer

    PubMed Central

    Coccetta, Marco; Migliaccio, Carla; La Mura, Francesco; Farinella, Eriberto; Galanou, Ioanna; Delmonaco, Pamela; Spizzirri, Alessandro; Napolitano, Vincenzo; Cattorini, Lorenzo; Milani, Diego; Cirocchi, Roberto; Sciannameo, Francesco

    2009-01-01

    Background Between 5 and 10% of the patients undergoing a colonoscopy cannot have a complete procedure mainly due to stenosing neoplastic lesion of rectum or distal colon. Nevertheless the elective surgical treatment concerning the stenosis is to be performed after the pre-operative assessment of the colonic segments upstream the cancer. The aim of this study is to illustrate our experience with the Computed Tomographic Colonography (CTC) for the pre-operative assessment of the entire colon in the patients with stenosing colorectal cancers. Methods From January 2005 till March 2009, we observed and treated surgically 43 patients with stenosing colorectal neoplastic lesions. All patients did not tolerate the pre-operative colonoscopy. For this reason they underwent a pre-operative CTC in order to have a complete assessment of the entire colon. All patients underwent a follow-up colonoscopy 3 months after the surgical treatment. The CTC results were compared with both macroscopic examination of the specimen and the follow-up coloscopy. Results The pre-operative CTC showed four synchronous lesions in four patients (9.3% of the cases). The macroscopic examination of the specimen revealed three small sessile polyps (3 - 4 mm in diameter) missed in the pre-operative assessment near the stenosing colorectal cancer. The follow-up colonoscopy showed four additional sessile polyps with a diameter between 3 - 11 mm in three patients. Our experience shows that CTC has a sensitivity of 83,7%. Conclusion In patients with stenosing colonic lesions, CTC allows to assess the entire colon pre-operatively avoiding the need of an intraoperative colonoscopy. More synchronous lesions are detected and treated at the time of the elective surgery for the stenosing cancer avoiding further surgery later on. PMID:19900286

  10. Association of genetic variants in lncRNA H19 with risk of colorectal cancer in a Chinese population

    PubMed Central

    Wang, Haixiao; Du, Mulong; Zhu, Lingjun; Chu, Haiyan; Zhang, Zhengdong; Wang, Meilin

    2016-01-01

    Objective The long non-coding RNA (lncRNA) gene, H19, has been involving in multiple biological functions, which also plays a vital role in colorectal cancer carcinogenesis. However, the association between genetic variants in H19 and colorectal cancer susceptibility has not been reported. In this study, we aim to explore whether H19 polymorphisms are related to the susceptibility of colorectal cancer. Methods We conducted a case-control study to evaluate the association between four selected single nucleotide polymorphisms (SNPs) (rs2839698, rs3024270, rs217727, and rs2735971) in H19 and the risk of colorectal cancer in a Chinese population. Results We found that individuals with rs2839698 A allele had a significantly increased risk of colorectal cancer, compared to those carrying G allele [odds ratio (OR) = 1.20, 95% confidence interval (CI) = 1.05–1.36 in additive model]. Further stratified analyses revealed that colon tumor site, well differentiated grade and Duke's stage of C/D were significantly associated with colorectal cancer risk (P < 0.05). Additionally, bioinformatic analysis showed that rs2839698 may change the crucial folding structures and alter the target microRNAs of H19. Conclusions Our results provided the evidence that rs2839698 in H19 was associated with elevated risk of colorectal cancer, which may be a potential biomarker for predicting colorectal cancer susceptibility. PMID:27027436

  11. Novel reversible selective inhibitor of nuclear export shows that CRM1 is a target in colorectal cancer cells.

    PubMed

    Niu, Mingshan; Chong, Yulong; Han, Yan; Liu, Xuejiao

    2015-01-01

    Colorectal cancer arises via a multistep carcinogenic process and the deregulation of multiple pathways. Thus, the simultaneous targeting of multiple pathways may be a promising therapeutic approach for colorectal treatment. CRM1 is an attractive cancer drug target, because it can regulate multiple pathways and tumor suppressor proteins. In this study, we investigated the anti-tumor activity of a novel reversible CRM1 inhibitor S109 in colorectal cancer. Our data demonstrate that S109 inhibits proliferation and induces cell cycle arrest in colorectal cancer cells. Mechanistically, we demonstrate that the activity of S109 is associated with the nuclear retention of major tumor suppress proteins. Furthermore, the Cys528 mutation of CRM1 prevented the ability of S109 to block nuclear export and inhibit the proliferation of colorectal cancer cells. Interestingly, S109 decreased the CRM1 protein level via proteasomal pathway. We argue that reversible CRM1 inhibitors but not irreversible inhibitors can induce the degradation of CRM1, because the dissociation of reversible inhibitors of CRM1 changes the conformation of CRM1. Taken together, these findings demonstrate that CRM1 is a valid target for the treatment of colorectal cancer and provide a basis for the development of S109 therapies for colorectal cancer.

  12. Colorectal cancer screening with virtual colonoscopy

    NASA Astrophysics Data System (ADS)

    Ge, Yaorong; Vining, David J.; Ahn, David K.; Stelts, David R.

    1999-05-01

    Early detection and removal of colorectal polyps have been proven to reduce mortality from colorectal carcinoma (CRC), the second leading cause of cancer deaths in the United States. Unfortunately, traditional techniques for CRC examination (i.e., barium enema, sigmoidoscopy, and colonoscopy) are unsuitable for mass screening because of either low accuracy or poor public acceptance, costs, and risks. Virtual colonoscopy (VC) is a minimally invasive alternative that is based on tomographic scanning of the colon. After a patient's bowel is optimally cleansed and distended with gas, a fast tomographic scan, typically helical computed tomography (CT), of the abdomen is performed during a single breath-hold acquisition. Two-dimensional (2D) slices and three-dimensional (3D) rendered views of the colon lumen generated from the tomographic data are then examined for colorectal polyps. Recent clinical studies conducted at several institutions including ours have shown great potential for this technology to be an effective CRC screening tool. In this paper, we describe new methods to improve bowel preparation, colon lumen visualization, colon segmentation, and polyp detection. Our initial results show that VC with the new bowel preparation and imaging protocol is capable of achieving accuracy comparable to conventional colonoscopy and our new algorithms for image analysis contribute to increased accuracy and efficiency in VC examinations.

  13. MTDH genetic variants in colorectal cancer patients

    PubMed Central

    Gnosa, Sebastian; Ticha, Ivana; Haapaniemi, Staffan; Sun, Xiao-Feng

    2016-01-01

    The colorectal carcinogenesis is a complex process encompassing genetic alterations. The oncoprotein AEG-1, encoded by the MTDH gene, was shown previously to be involved in colorectal cancer (CRC). The aim of this study was to determine the frequency and the spectrum of MTDH variants in tumor tissue, and their relationship to clinicopathological variables in CRC patients. The study included tumors from 356 unselected CRC patients. Mutation analysis of the MTDH gene, including coding region and adjacent intronic sequences, was performed by direct DNA sequencing. The corresponding normal colorectal tissue was analyzed in the carriers of exonic variant to confirm germline or somatic origin. We detected 42 intronic variants, where 25 were novel. Furthermore, we found 8 exonic variants of which four, one missense (c.977C > G-germline) and three frameshift mutations (c.533delA-somatic, c.1340dupA-unknown origin, c.1731delA-unknown origin), were novel. In silico prediction analyses suggested four deleterious variants (c.232G > T, c.533delA, c.1340dupA, and c.1731delA). There were no correlations between the MTDH variants and tumor stage, differentiation or patient survival. We described several novel exonic and intronic variants of the MTDH gene. The detection of likely pathogenic truncating mutations and alterations in functional protein domains indicate their clinical significance, although none of the variants had prognostic potential. PMID:26983693

  14. Common genetic variation in ETV6 is associated with colorectal cancer susceptibility

    PubMed Central

    Wang, Meilin; Gu, Dongying; Du, Mulong; Xu, Zhi; Zhang, Suzhan; Zhu, Lingjun; Lu, Jiachun; Zhang, Rui; Xing, Jinliang; Miao, Xiaoping; Chu, Haiyan; Hu, Zhibin; Yang, Lei; Tang, Cuiju; Pan, Lei; Du, Haina; Zhao, Jian; Du, Jiangbo; Tong, Na; Sun, Jielin; Shen, Hongbing; Xu, Jianfeng; Zhang, Zhengdong; Chen, Jinfei

    2016-01-01

    Genome-wide association studies (GWASs) have identified multiple susceptibility loci for colorectal cancer, but much of heritability remains unexplained. To identify additional susceptibility loci for colorectal cancer, here we perform a GWAS in 1,023 cases and 1,306 controls and replicate the findings in seven independent samples from China, comprising 5,317 cases and 6,887 controls. We find a variant at 12p13.2 associated with colorectal cancer risk (rs2238126 in ETV6, P=2.67 × 10−10). We replicate this association in an additional 1,046 cases and 1,076 controls of European ancestry (P=0.034). The G allele of rs2238126 confers earlier age at onset of colorectal cancer (P=1.98 × 10−6) and reduces the binding affinity of transcriptional enhancer MAX. The mRNA level of ETV6 is significantly lower in colorectal tumours than in paired normal tissues. Our findings highlight the potential importance of genetic variation in ETV6 conferring susceptibility to colorectal cancer. PMID:27145994

  15. Colorectal cancer development and advances in screening

    PubMed Central

    Simon, Karen

    2016-01-01

    Most colon tumors develop via a multistep process involving a series of histological, morphological, and genetic changes that accumulate over time. This has allowed for screening and detection of early-stage precancerous polyps before they become cancerous in individuals at average risk for colorectal cancer (CRC), which may lead to substantial decreases in the incidence of CRC. Despite the known benefits of early screening, CRC remains the second leading cause of cancer-related deaths in the United States. Hence, it is important for health care providers to have an understanding of the risk factors for CRC and various stages of disease development in order to recommend appropriate screening strategies. This article provides an overview of the histological/molecular changes that characterize the development of CRC. It describes the available CRC screening methods and their advantages and limitations and highlights the stages of CRC development in which each screening method is most effective. PMID:27486317

  16. Biomechanical investigation of colorectal cancer cells

    NASA Astrophysics Data System (ADS)

    Palmieri, Valentina; Lucchetti, Donatella; Maiorana, Alessandro; Papi, Massimiliano; Maulucci, Giuseppe; Ciasca, Gabriele; Svelto, Maria; De Spirito, Marco; Sgambato, Alessandro

    2014-09-01

    The nanomechanical properties of SW480 colon cancer cells were investigated using Atomic Force Microscopy. SW480 cells are composed of two sub-populations with different shape and invasiveness. These two cells populations showed similar adhesion properties while appeared significantly different in term of cells stiffness. Since cell stiffness is related to invasiveness and growth, we suggest elasticity as a useful parameter to distinguish invasive cells inside the colorectal tumor bulk and the high-resolution mechanical mapping as a promising diagnostic tool for the identification of malignant cells.

  17. Modelling multiscale aspects of colorectal cancer

    NASA Astrophysics Data System (ADS)

    van Leeuwen, Ingeborg M. M.; Byrne, Helen M.; Johnston, Matthew D.; Edwards, Carina M.; Chapman, S. Jonathan; Bodmer, Walter F.; Maini, Philip K.

    2008-01-01

    Colorectal cancer (CRC) is responsible for nearly half a million deaths annually world-wide [11]. We present a series of mathematical models describing the dynamics of the intestinal epithelium and the kinetics of the molecular pathway most commonly mutated in CRC, the Wnt signalling network. We also discuss how we are coupling such models to build a multiscale model of normal and aberrant guts. This will enable us to combine disparate experimental and clinical data, to investigate interactions between phenomena taking place at different levels of organisation and, eventually, to test the efficacy of new drugs on the system as a whole.

  18. Dendritic cell-based cancer immunotherapy for colorectal cancer.

    PubMed

    Kajihara, Mikio; Takakura, Kazuki; Kanai, Tomoya; Ito, Zensho; Saito, Keisuke; Takami, Shinichiro; Shimodaira, Shigetaka; Okamoto, Masato; Ohkusa, Toshifumi; Koido, Shigeo

    2016-05-01

    Colorectal cancer (CRC) is one of the most common cancers and a leading cause of cancer-related mortality worldwide. Although systemic therapy is the standard care for patients with recurrent or metastatic CRC, the prognosis is extremely poor. The optimal sequence of therapy remains unknown. Therefore, alternative strategies, such as immunotherapy, are needed for patients with advanced CRC. This review summarizes evidence from dendritic cell-based cancer immunotherapy strategies that are currently in clinical trials. In addition, we discuss the possibility of antitumor immune responses through immunoinhibitory PD-1/PD-L1 pathway blockade in CRC patients. PMID:27158196

  19. Dendritic cell-based cancer immunotherapy for colorectal cancer.

    PubMed

    Kajihara, Mikio; Takakura, Kazuki; Kanai, Tomoya; Ito, Zensho; Saito, Keisuke; Takami, Shinichiro; Shimodaira, Shigetaka; Okamoto, Masato; Ohkusa, Toshifumi; Koido, Shigeo

    2016-05-01

    Colorectal cancer (CRC) is one of the most common cancers and a leading cause of cancer-related mortality worldwide. Although systemic therapy is the standard care for patients with recurrent or metastatic CRC, the prognosis is extremely poor. The optimal sequence of therapy remains unknown. Therefore, alternative strategies, such as immunotherapy, are needed for patients with advanced CRC. This review summarizes evidence from dendritic cell-based cancer immunotherapy strategies that are currently in clinical trials. In addition, we discuss the possibility of antitumor immune responses through immunoinhibitory PD-1/PD-L1 pathway blockade in CRC patients.

  20. Dendritic cell-based cancer immunotherapy for colorectal cancer

    PubMed Central

    Kajihara, Mikio; Takakura, Kazuki; Kanai, Tomoya; Ito, Zensho; Saito, Keisuke; Takami, Shinichiro; Shimodaira, Shigetaka; Okamoto, Masato; Ohkusa, Toshifumi; Koido, Shigeo

    2016-01-01

    Colorectal cancer (CRC) is one of the most common cancers and a leading cause of cancer-related mortality worldwide. Although systemic therapy is the standard care for patients with recurrent or metastatic CRC, the prognosis is extremely poor. The optimal sequence of therapy remains unknown. Therefore, alternative strategies, such as immunotherapy, are needed for patients with advanced CRC. This review summarizes evidence from dendritic cell-based cancer immunotherapy strategies that are currently in clinical trials. In addition, we discuss the possibility of antitumor immune responses through immunoinhibitory PD-1/PD-L1 pathway blockade in CRC patients. PMID:27158196

  1. RNF43 is frequently mutated in colorectal and endometrial cancers

    PubMed Central

    Giannakis, Marios; Hodis, Eran; Mu, Xinmeng Jasmine; Yamauchi, Mai; Rosenbluh, Joseph; Cibulskis, Kristian; Saksena, Gordon; Lawrence, Michael S.; Qian, ZhiRong; Nishihara, Reiko; Van Allen, Eliezer M.; Hahn, William C.; Gabriel, Stacey B.; Lander, Eric S.; Getz, Gad; Ogino, Shuji; Fuchs, Charles S.; Garraway, Levi A.

    2014-01-01

    We report somatic mutations of RNF43 in over 18% of colorectal adenocarcinomas and endometrial carcinomas. RNF43 encodes an E3 ubiquitin ligase that negatively regulates Wnt signaling. Truncating mutations of RNF43 are more prevalent in microsatellite-unstable tumors and show mutual exclusivity with inactivating APC mutations in colorectal adenocarcinomas. These results indicate that RNF43 is one of the most commonly mutated genes in colorectal and endometrial cancers. PMID:25344691

  2. Food groups and colorectal cancer risk

    PubMed Central

    Levi, F; Pasche, C; La Vecchia, C; Lucchini, F; Franceschi, S

    1999-01-01

    Most studies of diet and colorectal cancer have considered nutrients and micronutrients, but the role of foods or food groups remains open to debate. To elucidate the issue, we examined data from a case–control study conducted between 1992 and 1997 in the Swiss canton of Vaud. Cases were 223 patients (142 men, 81 women) with incident, histologically confirmed colon (n = 119) or rectal (n = 104) cancer (median age 63 years), linked with the Cancer Registry of the Swiss Canton of Vaud, and controls were 491 subjects (211 men, 280 women, median age 58 years) admitted to the same university hospital for a wide spectrum of acute non-neoplastic conditions unrelated to long-term modifications of diet. Odds ratios (OR) were obtained after allowance for age, sex, education, smoking, alcohol, body mass index, physical activity and total energy intake. Significant associations were observed for refined grain (OR = 1.32 for an increase of one serving per day), and red meat (OR = 1.54), pork and processed meat (OR = 1.27), alcohol (OR = 1.28), and significant protections for whole grain (OR = 0.85), raw (OR = 0.85) and cooked vegetables (OR = 0.69), citrus (OR = 0.86) and other fruits (OR = 0.85), and for coffee (OR = 0.73). Garlic was also protective (OR = 0.32 for the highest tertile of intake). These findings in a central European population support the hypothesis that a diet rich in refined grains and red meat increases the risk of colorectal cancer; they, therefore, support the recommendation to substitute whole grains for refined grain, to limit meat intake, and to increase fruit and vegetable consumption. © 1999 Cancer Research Campaign PMID:10098773

  3. Colonoscopy in Colorectal Cancer Screening: Current Aspects.

    PubMed

    Triantafillidis, John K; Vagianos, Constantine; Malgarinos, George

    2015-09-01

    Colonoscopy represents a very important diagnostic modality for screening for colorectal cancer, because it has the ability to both detect and effectively remove pro-malignant and malignant lesions. It is recommended by almost all international and national gastroenterology and cancer societies, as an initial screening modality or, following a positive fecal occult blood test, to be performed every 10 years in individuals of average risk starting from the age of 50. However, a significant problem is the so-called post-screening (interval) polyps and cancers found some years after the index colonoscopy. In order to reduce the rate of interval cancers it is extremely necessary to optimize the quality and effectiveness of colonoscopy. Bowel preparation is of paramount importance for both accurate diagnosis and subsequent treatment of lesions found on colonoscopy. The quality of bowel preparation could be significantly improved by splitting the dose regimens, a strategy that has been shown to be superior to single-dose regimen. A good endoscopic technique and optimal withdrawal time offering adequate time for inspection, would further optimize the rate of cecal intubation and the number of lesions detected. During the last years, sophisticated devices have been introduced that would further facilitate cecal intubation. The percentage of total colonoscopies is now super-passing the level of 95 % allowing the adenoma detection rate to be greater than the suggestive level of 25 % in men and 15 % in women. This review aims to provide the reader with the current knowledge concerning indications, usefulness, limitations and future perspectives of this probably most important screening technique for colorectal cancer available today. PMID:27217671

  4. Protein kinase d as a potential chemotherapeutic target for colorectal cancer.

    PubMed

    Wei, Ning; Chu, Edward; Wipf, Peter; Schmitz, John C

    2014-05-01

    Protein kinase D (PKD) signaling plays a critical role in the regulation of DNA synthesis, proliferation, cell survival, adhesion, invasion/migration, motility, and angiogenesis. To date, relatively little is known about the potential role of PKD in the development and/or progression of human colorectal cancer. We evaluated the expression of different PKD isoforms in colorectal cancer and investigated the antitumor activity of PKD inhibitors against human colorectal cancer. PKD2 was the dominant isoform expressed in human colon cancer cells. PKD3 expression was also observed but PKD1 expression, at both the RNA and protein levels, was not detected. Suppression of PKD using the small molecule inhibitors CRT0066101 and kb-NB142-70 resulted in low micromolar in vitro antiproliferative activity against multiple human colorectal cancer cell lines. Drug treatment was associated with dose-dependent suppression of PKD2 activation. Incubation with CRT0066101 resulted in G(2)-M phase arrest and induction of apoptosis in human colorectal cancer cells. Further studies showed that CRT0066101 treatment gave rise to a dose-dependent increase in expression of cleaved PARP and activated caspase-3, in addition to inhibition of AKT and ERK signaling, and suppression of NF-κB activity. Transfection of PKD2-targeted siRNAs resulted in similar effects on downstream pathways as observed with small molecule inhibitors. Daily administration of CRT0066101 resulted in significant inhibition of tumor growth in HCT116 xenograft nude mice. Taken together, our studies show that PKD plays a significant role in mediating growth signaling in colorectal cancer and may represent a novel chemotherapeutic target for the treatment of colorectal cancer. PMID:24634417

  5. Dietary flavonoid intake and risk of stomach and colorectal cancer.

    PubMed

    Woo, Hae Dong; Kim, Jeongseon

    2013-02-21

    Stomach and colorectal cancers are common cancers and leading causes of cancer deaths. Because the alimentary tract can interact directly with dietary components, stomach and colorectal cancer may be closely related to dietary intake. We systematically searched published literature written in English via PubMed by searching for terms related to stomach and colorectal cancer risk and dietary flavonoids up to June 30, 2012. Twenty-three studies out of 209 identified articles were finally selected for the analysis. Log point effect estimates and the corresponding standard errors were calculated using covariate-adjusted point effect estimates and 95%CIs from the selected studies. Total dietary flavonoid intake was not associated with a reduced risk of colorectal or stomach cancer [odds ratio (OR) (95%CI) = 1.00 (0.90-1.11) and 1.07 (0.70-1.61), respectively]. Among flavonoid subclasses, the intake of flavonols, flavan-3-ols, anthocyanidins, and proanthocyanidins showed a significant inverse association with colorectal cancer risk [OR (95%CI) = 0.71 (0.63-0.81), 0.88 (0.79-0.97), 0.68 (0.56-0.82), and 0.72 (0.61-0.85), respectively]. A significant association was found only between flavonols and stomach cancer risk based on a limited number of selected studies [OR (95%CI) = 0.68 (0.46-0.99)]. In the summary estimates from case-control studies, all flavonoid subclasses except flavones and flavanones were inversely associated with colorectal cancer risk, whereas neither total flavonoids nor any subclasses of flavonoids were associated with colorectal cancer risk in the summary estimates based on the cohort studies. The significant association between flavonoid subclasses and cancer risk might be closely related to bias derived from the case-control design. There was no clear evidence that dietary flavonoids are associated with reduced risk of stomach and colorectal cancer.

  6. Colorectal cancer prognosis twenty years later

    PubMed Central

    Bujanda, Luis; Sarasqueta, Cristina; Hijona, Elisabeth; Hijona, Lander; Cosme, Angel; Gil, Ines; Elorza, Jose Luis; Asensio, Jose I; Larburu, Santiago; Enríquez-Navascués, José M; Jover, Rodrigo; Balaguer, Francesc; Llor, Xavier; Bessa, Xavier; Andreu, Montserrat; Paya, Artemio; Castells, Antoni; Association, Gastrointestinal Oncology Group of the Spanish Gastroenterological

    2010-01-01

    AIM: To evaluate changes in colorectal cancer (CRC) survival over the last 20 years. METHODS: We compared two groups of consecutive CRC patients that were prospectively recruited: Group I included 1990 patients diagnosed between 1980 and 1994. Group II included 871 patients diagnosed in 2001. RESULTS: The average follow up time was 21 mo (1-229) for Group I and 50 mo (1-73.4) for Group II. Overall median survival was significantly longer in Group II than in Group I (73 mo vs 25 mo, P < 0.001) and the difference was significant for all tumor stages. Post surgical mortality was 8% for Group Iand 2% for Group II (P < 0.001). Only 17% of GroupI patients received chemotherapy compared with 50% of Group II patients (P < 0.001). CONCLUSION: Survival in colorectal cancer patients has doubled over the past 20 years. This increase seems to be partly due to the generalization in the administration of chemotherapy and to the decrease of post surgical mortality. PMID:20143465

  7. Role of physical activity and diet after colorectal cancer diagnosis.

    PubMed

    Van Blarigan, Erin L; Meyerhardt, Jeffrey A

    2015-06-01

    This review summarizes the evidence regarding physical activity and diet after colorectal cancer diagnosis in relation to quality of life, disease recurrence, and survival. There have been extensive reports on adiposity, inactivity, and certain diets, particularly those high in red and processed meats, and increased risk of colorectal cancer. Only in the past decade have data emerged on how such lifestyle factors are associated with outcomes in colorectal cancer survivors. Prospective observational studies have consistently reported that physical activity after colorectal cancer diagnosis reduces mortality. A meta-analysis estimated that each 15 metabolic equivalent task-hour per week increase in physical activity after colorectal cancer diagnosis was associated with a 38% lower risk of mortality. No randomized controlled trials have been completed to confirm that physical activity lowers risk of mortality among colorectal cancer survivors; however, trials have shown that physical activity, including structured exercise, is safe for colorectal cancer survivors (localized to metastatic stage, during and after treatment) and improves cardiorespiratory fitness and physical function. In addition, prospective observational studies have suggested that a Western dietary pattern, high carbohydrate intake, and consuming sugar-sweetened beverages after diagnosis may increase risk of colorectal cancer recurrence and mortality, but these data are limited to single analyses from one of two US cohorts. Additional data from prospective studies and randomized controlled trials are needed. Nonetheless, on the basis of the available evidence, it is reasonable to counsel colorectal cancer survivors to engage in regular physical activity and limit consumption of refined carbohydrates, red and processed meats, and sugar-sweetened beverages.

  8. Role of Physical Activity and Diet After Colorectal Cancer Diagnosis

    PubMed Central

    Van Blarigan, Erin L.; Meyerhardt, Jeffrey A.

    2015-01-01

    This review summarizes the evidence regarding physical activity and diet after colorectal cancer diagnosis in relation to quality of life, disease recurrence, and survival. There have been extensive reports on adiposity, inactivity, and certain diets, particularly those high in red and processed meats, and increased risk of colorectal cancer. Only in the past decade have data emerged on how such lifestyle factors are associated with outcomes in colorectal cancer survivors. Prospective observational studies have consistently reported that physical activity after colorectal cancer diagnosis reduces mortality. A meta-analysis estimated that each 15 metabolic equivalent task-hour per week increase in physical activity after colorectal cancer diagnosis was associated with a 38% lower risk of mortality. No randomized controlled trials have been completed to confirm that physical activity lowers risk of mortality among colorectal cancer survivors; however, trials have shown that physical activity, including structured exercise, is safe for colorectal cancer survivors (localized to metastatic stage, during and after treatment) and improves cardiorespiratory fitness and physical function. In addition, prospective observational studies have suggested that a Western dietary pattern, high carbohydrate intake, and consuming sugar-sweetened beverages after diagnosis may increase risk of colorectal cancer recurrence and mortality, but these data are limited to single analyses from one of two US cohorts. Additional data from prospective studies and randomized controlled trials are needed. Nonetheless, on the basis of the available evidence, it is reasonable to counsel colorectal cancer survivors to engage in regular physical activity and limit consumption of refined carbohydrates, red and processed meats, and sugar-sweetened beverages. PMID:25918293

  9. Proteomics for discovery of candidate colorectal cancer biomarkers

    PubMed Central

    Álvarez-Chaver, Paula; Otero-Estévez, Olalla; Páez de la Cadena, María; Rodríguez-Berrocal, Francisco J; Martínez-Zorzano, Vicenta S

    2014-01-01

    Colorectal cancer (CRC) is the second most common cause of cancer-related deaths in Europe and other Western countries, mainly due to the lack of well-validated clinically useful biomarkers with enough sensitivity and specificity to detect this disease at early stages. Although it is well known that the pathogenesis of CRC is a progressive accumulation of mutations in multiple genes, much less is known at the proteome level. Therefore, in the last years many proteomic studies have been conducted to find new candidate protein biomarkers for diagnosis, prognosis and as therapeutic targets for this malignancy, as well as to elucidate the molecular mechanisms of colorectal carcinogenesis. An important advantage of the proteomic approaches is the capacity to look for multiple differentially expressed proteins in a single study. This review provides an overview of the recent reports describing the different proteomic tools used for the discovery of new protein markers for CRC such as two-dimensional electrophoresis methods, quantitative mass spectrometry-based techniques or protein microarrays. Additionally, we will also focus on the diverse biological samples used for CRC biomarker discovery such as tissue, serum and faeces, besides cell lines and murine models, discussing their advantages and disadvantages, and summarize the most frequently identified candidate CRC markers. PMID:24744574

  10. Role of phytochemicals in colorectal cancer prevention

    PubMed Central

    Li, Yu-Hua; Niu, Yin-Bo; Sun, Yang; Zhang, Feng; Liu, Chang-Xu; Fan, Lei; Mei, Qi-Bing

    2015-01-01

    Although the incidence of colorectal cancer (CRC) has been declining in recent decades, it remains a major public health issue as a leading cause of cancer mortality and morbidity worldwide. Prevention is one milestone for this disease. Extensive study has demonstrated that a diet containing fruits, vegetables, and spices has the potential to prevent CRC. The specific constituents in the dietary foods which are responsible for preventing CRC and the possible mechanisms have also been investigated extensively. Various phytochemicals have been identified in fruits, vegetables, and spices which exhibit chemopreventive potential. In this review article, chemopreventive effects of phytochemicals including curcumin, polysaccharides (apple polysaccharides and mushroom glucans), saponins (Paris saponins, ginsenosides and soy saponins), resveratrol, and quercetin on CRC and the mechanisms are discussed. This review proposes the need for more clinical evidence for the effects of phytochemicals against CRC in large trials. The conclusion of the review is that these phytochemicals might be therapeutic candidates in the campaign against CRC. PMID:26309353

  11. Probiotics, prebiotics and colorectal cancer prevention.

    PubMed

    Ambalam, Padma; Raman, Maya; Purama, Ravi Kiran; Doble, Mukesh

    2016-02-01

    Colorectal cancer (CRC), the third major cause of mortality among various cancer types in United States, has been increasing in developing countries due to varying diet and dietary habits and occupational hazards. Recent evidences showed that composition of gut microbiota could be associated with the development of CRC and other gut dysbiosis. Modulation of gut microbiota by probiotics and prebiotics, either alone or in combination could positively influence the cross-talk between immune system and microbiota, would be beneficial in preventing inflammation and CRC. In this review, role of probiotics and prebiotics in the prevention of CRC has been discussed. Various epidemiological and experimental studies, specifically gut microbiome research has effectively improved the understanding about the role of probiotics and microbial treatment as anticarcinogenic agents. A few human studies support the beneficial effect of probiotics and prebiotics; hence, comprehensive understanding is urgent to realize the clinical applications of probiotics and prebiotics in CRC prevention.

  12. Pharmacogenomics and -genetics in colorectal cancer.

    PubMed

    Pohl, Alexandra; Lurje, Georg; Manegold, Philipp C; Lenz, Heinz-Josef

    2009-05-20

    Despite recent progress in our knowledge about the development and therapy of colorectal cancer (CRC), it still remains one of the major cancer related deaths throughout the world. With the introduction of new cytotoxic and targeting agents a significant improvement in progression-free and overall survival has been achieved. However, a significant percentage (40-50%) of patients do not experience beneficial effects and suffer from severe toxicities. It will be critical to identify molecular markers, which may help to assess therapeutic response and outcome in CRC. Validation of predictive and prognostic molecular markers will enable oncologists to tailor patient specific treatment strategies for the individual patient according to the molecular profile of both the patient and their tumor. Individualized therapy will help to improve therapeutic efficacy and to minimize toxicities and therapeutic expenses.

  13. Colorectal cancer carcinogenesis: a review of mechanisms

    PubMed Central

    Tariq, Kanwal; Ghias, Kulsoom

    2016-01-01

    Colorectal cancer (CRC) is the second most common cancer in women and the third most common in men globally. CRC arises from one or a combination of chromosomal instability, CpG island methylator phenotype, and microsatellite instability. Genetic instability is usually caused by aneuploidy and loss of heterozygosity. Mutations in the tumor suppressor or cell cycle genes may also lead to cellular transformation. Similarly, epigenetic and/or genetic alterations resulting in impaired cellular pathways, such as DNA repair mechanism, may lead to microsatellite instability and mutator phenotype. Non-coding RNAs, more importantly microRNAs and long non-coding RNAs have also been implicated at various CRC stages. Understanding the specific mechanisms of tumorigenesis and the underlying genetic and epigenetic traits is critical in comprehending the disease phenotype. This paper reviews these mechanisms along with the roles of various non-coding RNAs in CRCs. PMID:27144067

  14. The gastrointestinal microbiota and colorectal cancer

    PubMed Central

    Dulal, Santosh; Deveaux, April; Jovov, Biljana; Han, Xuesong

    2014-01-01

    The human gut is home to a complex and diverse microbiota that contributes to the overall homeostasis of the host. Increasingly, the intestinal microbiota is recognized as an important player in human illness such as colorectal cancer (CRC), inflammatory bowel diseases, and obesity. CRC in itself is one of the major causes of cancer mortality in the Western world. The mechanisms by which bacteria contribute to CRC are complex and not fully understood, but increasing evidence suggests a link between the intestinal microbiota and CRC as well as diet and inflammation, which are believed to play a role in carcinogenesis. It is thought that the gut microbiota interact with dietary factors to promote chronic inflammation and CRC through direct influence on host cell physiology, cellular homeostasis, energy regulation, and/or metabolism of xenobiotics. This review provides an overview on the role of commensal gut microbiota in the development of human CRC and explores its association with diet and inflammation. PMID:25540232

  15. Primary prevention of colorectal cancer: lifestyle, nutrition, exercise.

    PubMed

    Martínez, María Elena

    2005-01-01

    The past two decades have provided a vast amount of literature related to the primary prevention of colorectal cancer. Large international variation in colorectal cancer incidence and mortality rates and the prominent increases in the incidence of colorectal cancer in groups that migrated from low- to high-incidence areas provided important evidence that lifestyle factors influence the development of this malignancy. Moreover, there is convincing evidence from epidemiological and experimental studies that dietary intake is an important etiological factor in colorectal neoplasia. Although the precise mechanisms have not been clarified, several lifestyle factors are likely to have a major impact on colorectal cancer development. Physical inactivity and to a lesser extent, excess body weight, are consistent risk factors for colon cancer. Exposure to tobacco products early in life is associated with a higher risk of developing colorectal neoplasia. Diet and nutritional factors are also clearly important. Diets high in red and processed meat increase risk. Excess alcohol consumption, probably in combination with a diet low in some micronutrients such as folate and methionine, appear to increase risk. There is also recent evidence supporting a protective effect of calcium and vitamin D in the etiology of colorectal neoplasia. The relationship between intake of dietary fiber and risk of colon cancer has been studied for three decades but the results are still inconclusive. However, some micronutrients or phytochemicals in fiber-rich foods may be important; folic acid is one such micronutrient that has been shown to protect against the development of colorectal neoplasia and is currently being studied in intervention trials of adenoma recurrence. The overwhelming evidence indicates that primary prevention of colon cancer is feasible. Continued focus on primary prevention of colorectal cancer, in combination with efforts aimed at screening and surveillance, will be vital in

  16. Apoptotic pathways as a therapeutic target for colorectal cancer treatment.

    PubMed

    Abraha, Aman M; Ketema, Ezra B

    2016-08-15

    Colorectal cancer is the second leading cause of death from cancer among adults. The disease begins as a benign adenomatous polyp, which develops into an advanced adenoma with high-grade dysplasia and then progresses to an invasive cancer. Appropriate apoptotic signaling is fundamentally important to preserve a healthy balance between cell death and cell survival and in maintaining genome integrity. Evasion of apoptotic pathway has been established as a prominent hallmark of several cancers. During colorectal cancer development, the balance between the rates of cell growth and apoptosis that maintains intestinal epithelial cell homeostasis gets progressively disturbed. Evidences are increasingly available to support the hypothesis that failure of apoptosis may be an important factor in the evolution of colorectal cancer and its poor response to chemotherapy and radiation. The other reason for targeting apoptotic pathway in the treatment of cancer is based on the observation that this process is deregulated in cancer cells but not in normal cells. As a result, colorectal cancer therapies designed to stimulate apoptosis in target cells would play a critical role in controlling its development and progression. A better understanding of the apoptotic signaling pathways, and the mechanisms by which cancer cells evade apoptotic death might lead to effective therapeutic strategies to inhibit cancer cell proliferation with minimal toxicity and high responses to chemotherapy. In this review, we analyzed the current understanding and future promises of apoptotic pathways as a therapeutic target in colorectal cancer treatment. PMID:27574550

  17. Apoptotic pathways as a therapeutic target for colorectal cancer treatment

    PubMed Central

    Abraha, Aman M; Ketema, Ezra B

    2016-01-01

    Colorectal cancer is the second leading cause of death from cancer among adults. The disease begins as a benign adenomatous polyp, which develops into an advanced adenoma with high-grade dysplasia and then progresses to an invasive cancer. Appropriate apoptotic signaling is fundamentally important to preserve a healthy balance between cell death and cell survival and in maintaining genome integrity. Evasion of apoptotic pathway has been established as a prominent hallmark of several cancers. During colorectal cancer development, the balance between the rates of cell growth and apoptosis that maintains intestinal epithelial cell homeostasis gets progressively disturbed. Evidences are increasingly available to support the hypothesis that failure of apoptosis may be an important factor in the evolution of colorectal cancer and its poor response to chemotherapy and radiation. The other reason for targeting apoptotic pathway in the treatment of cancer is based on the observation that this process is deregulated in cancer cells but not in normal cells. As a result, colorectal cancer therapies designed to stimulate apoptosis in target cells would play a critical role in controlling its development and progression. A better understanding of the apoptotic signaling pathways, and the mechanisms by which cancer cells evade apoptotic death might lead to effective therapeutic strategies to inhibit cancer cell proliferation with minimal toxicity and high responses to chemotherapy. In this review, we analyzed the current understanding and future promises of apoptotic pathways as a therapeutic target in colorectal cancer treatment. PMID:27574550

  18. Primary and Secondary Prevention of Colorectal Cancer

    PubMed Central

    Tárraga López, Pedro J; Albero, Juan Solera; Rodríguez-Montes, José Antonio

    2014-01-01

    INTRODUCTION Cancer is a worldwide problem as it will affect one in three men and one in four women during their lifetime. Colorectal cancer (CRC) is the third most frequent cancer in men, after lung and prostate cancer, and is the second most frequent cancer in women after breast cancer. It is also the third cause of death in men and women separately, and is the second most frequent cause of death by cancer if both genders are considered together. CRC represents approximately 10% of deaths by cancer. Modifiable risk factors of CRC include smoking, physical inactivity, being overweight and obesity, eating processed meat, and drinking alcohol excessively. CRC screening programs are possible only in economically developed countries. However, attention should be paid in the future to geographical areas with ageing populations and a western lifestyle.19,20 Sigmoidoscopy screening done with people aged 55–64 years has been demonstrated to reduce the incidence of CRC by 33% and mortality by CRC by 43%. OBJECTIVE To assess the effect on the incidence and mortality of CRC diet and lifestyle and to determine the effect of secondary prevention through early diagnosis of CRC. METHODOLOGY: A comprehensive search of Medline and Pubmed articles related to primary and secondary prevention of CRC and subsequently, a meta-analysis of the same blocks are performed. RESULTS 225 articles related to primary or secondary prevention of CRC were retrieved. Of these 145 were considered valid on meta-analysis: 12 on epidemiology, 56 on diet and lifestyle, and over 77 different screenings for early detection of CRC. Cancer is a worldwide problem as it will affect one in three men and one in four women during their lifetime. There is no doubt whatsoever which environmental factors, probably diet, may account for these cancer rates. Excessive alcohol consumption and cholesterol-rich diet are associated with a high risk of colon cancer. A diet poor in folic acid and vitamin B6 is also

  19. Eicosanoid pathway in colorectal cancer: Recent updates

    PubMed Central

    Tuncer, Sinem; Banerjee, Sreeparna

    2015-01-01

    Enzymatic metabolism of the 20C polyunsaturated fatty acid (PUFA) arachidonic acid (AA) occurs via the cyclooxygenase (COX) and lipoxygenase (LOX) pathways, and leads to the production of various bioactive lipids termed eicosanoids. These eicosanoids have a variety of functions, including stimulation of homeostatic responses in the cardiovascular system, induction and resolution of inflammation, and modulation of immune responses against diseases associated with chronic inflammation, such as cancer. Because chronic inflammation is essential for the development of colorectal cancer (CRC), it is not surprising that many eicosanoids are implicated in CRC. Oftentimes, these autacoids work in an antagonistic and highly temporal manner in inflammation; therefore, inhibition of the pro-inflammatory COX-2 or 5-LOX enzymes may subsequently inhibit the formation of their essential products, or shunt substrates from one pathway to another, leading to undesirable side-effects. A better understanding of these different enzymes and their products is essential not only for understanding the importance of eicosanoids, but also for designing more effective drugs that solely target the inflammatory molecules found in both chronic inflammation and cancer. In this review, we have evaluated the cancer promoting and anti-cancer roles of different eicosanoids in CRC, and highlighted the most recent literature which describes how those molecules affect not only tumor tissue, but also the tumor microenvironment. Additionally, we have attempted to delineate the roles that eicosanoids with opposing functions play in neoplastic transformation in CRC through their effects on proliferation, apoptosis, motility, metastasis, and angiogenesis. PMID:26557000

  20. Epigenetic Alterations in Colorectal Cancer: Emerging Biomarkers

    PubMed Central

    Okugawa, Yoshinaga; Grady, William M.; Goel, Ajay

    2015-01-01

    Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide. One of the fundamental processes driving the initiation and progression of CRC is the accumulation of a variety of genetic and epigenetic changes in colon epithelial cells. Over the past decade, major advances have been made in our understanding of cancer epigenetics, particularly regarding aberrant DNA methylation, microRNA (miRNA) and noncoding RNA deregulation, and alterations in histone modification states. Assessment of the colon cancer “epigenome” has revealed that virtually all CRCs have aberrantly methylated genes and altered miRNA expression. The average CRC methylome has hundreds to thousands of abnormally methylated genes and dozens of altered miRNAs. As with gene mutations in the cancer genome, a subset of these epigenetic alterations, called driver events, is presumed to have a functional role in CRC. In addition, the advances in our understanding of epigenetic alterations in CRC have led to these alterations being developed as clinical biomarkers for diagnostic, prognostic and therapeutic applications. Progress in this field suggests that these epigenetic alterations will be commonly used in the near future to direct the prevention and treatment of CRC. PMID:26216839

  1. Endometrial metastasis of colorectal cancer with coincident endometrial adenocarcinoma

    PubMed Central

    Colling, Richard; Lopes, Tito; Das, Nagiindra; Mathew, Joe

    2010-01-01

    Metastasis to the uterine corpus is uncommon and secondary colorectal tumours of the endometrium are rare. We describe a uterine tumour with components of both primary endometrial and metastatic colorectal carcinomata. In this case, a 72-year-old obese woman presented with a 2-week history of postmenopausal bleeding per vaginum and weight loss. She had an abdominoperineal resection 3 years previously for a Dukes stage B rectal carcinoma. A transvaginal ultrasonography showed a thickened endometrium. Histology immunophenotyping showed a CK7+, CK20+, CA125− and CEA+ colorectal metastasis (a profile consistent with her previous cancer) associated with a primary CK7+, CK20−, CA125+ and CEA− endometroid endometrial adenocarcinoma. We conclude this represents endometrial metastasis of colorectal carcinoma with coincident primary endometrial adenocarcinoma. We speculate as to whether the endometrial carcinoma arose de novo or was induced by the colorectal metastasis, or whether the primary endometrial tumour provided a fertile site for the colorectal metastasis. PMID:22791861

  2. Biomarkers, Bundled Payments, and Colorectal Cancer Care

    PubMed Central

    Lynch, Patrick; Raju, Gottumukkala; Rodriguez, Alma; Burke, Thomas; Hafemeister, Lisa; Hawk, Ernest; Wu, Xifeng; DuBois, Raymond N.

    2012-01-01

    Changes in the management of cancers such as colorectal cancer (CRC) are urgently needed, as such cancers continue to be one of the most commonly diagnosed cancers; CRC accounts for 21% of all cancers and is responsible for mortalities second only to lung cancer in the United States. A comprehensive science-driven approach towards markedly improved early detection/screening to efficacious targeted therapeutics with clear diagnostic and prognostic markers is essential. In addition, further changes addressing rising costs, stemming from recent health care reform measures, will be brought about in part by changes in how care is reimbursed. For oncology, the advances in genomics and biomarkers have the potential to define subsets of patients who have a prognosis or response to a particular type of therapy that differs from the mean. Better definition of a cancer’s behavior will facilitate developing care plans tailored to the patient. One method under study is episode-based payment or bundling, where one payment is made to a provider organization to cover all expenses associated with a discrete illness episode. Payments will be based on the average cost of care, with providers taking on a risk for overutilization and outliers. For providers to thrive in this environment, they will need to know what care a patient will require and the costs of that care. A science-driven “personalized approach” to cancer care has the potential to produce better outcomes with reductions in the use of ineffectual therapies and costs. This promising scenario is still in the future, but progress is being made, and the shape of things to come for cancer care in the age of genomics is becoming clearer. PMID:22893787

  3. Primary and recurrent colorectal cancer masquerading as gynaecological malignancy.

    PubMed

    Brand, A; Scurry, J; Planner, R; Leung, S

    1996-05-01

    To make clinicians more aware of the phenomenon of primary and recurrent colorectal and anal carcinoma masquerading as primary gynaecological malignancy, we reviewed the records of 8 women referred to our gynaecological oncology unit with primary colorectal cancer (1), recurrent colorectal cancer (6) and primary anal cancer (1). Seven of these patients presented with abnormal vaginal bleeding or discharge. All patients had Papanicolaou smears performed; 7 were abnormal and 1 unsuitable for cytological assessment. None of the 6 patients with recurrent carcinoma had been previously treated with more than standard anterior or abdominoperineal resection; no radiotherapy had been given, and only 1 patient had received chemotherapy. These patients were treated in our gynaecological oncology unit for their recurrence by surgery and/or chemotherapy and/or irradiation. All 6 had further recurrences in the pelvis despite this aggressive therapy. Follow-up of colorectal cancer in women should involve gynaecological history, pelvirectal examination and Pap smear at each visit. Correct diagnosis of the colorectal origin of a genital tract tumour is made on careful history, examination and biopsy. An abnormal Pap smear may be the first indication of recurrent colorectal cancer in the cervix and vagina, although most patients ultimately present with abnormal vaginal bleeding. The presence of a tumour invading both cervix and posterior vaginal wall is suggestive of spread from a colorectal tumour compared to the more common lateral spread of a cervical primary.

  4. Molecular Taxonomy and Tumourigenesis of Colorectal Cancer.

    PubMed

    Biswas, S; Holyoake, D; Maughan, T S

    2016-02-01

    Over the last 5 years there has been a surge in interest in the molecular classification of colorectal cancer. The effect of molecular subtyping on current treatment decisions is limited to avoidance of adjuvant 5-fluorouracil chemotherapy in stage II microsatellite unstable-high disease and avoidance of epidermal growth factor receptor-targeted antibodies in extended RAS mutant tumours. The emergence of specific novel combination therapy for the BRAF-mutant cohort and of the microsatellite unstable-high cohort as a responsive group to immune checkpoint inhibition shows the growing importance of a clinically relevant molecular taxonomy. Clinical trials such as the Medical Research Council FOCUS4 trial using biomarkers to select patients for specific therapies are currently open and testing such approaches. The integration of mutation, gene expression and pathological analyses is refining our understanding of the biological subtypes within colorectal cancer. Sharing of data sets of parallel sequencing and gene expression of thousands of cancers among independent groups has allowed the description of disease subsets and the need for a validated consensus classification has become apparent. This biological understanding of the disease is a key step forward in developing a stratified approach to patient management. The discovery of stratifiers that predict a response to existing and emerging therapies will enable better use of these treatments. Improved scientific understanding of the biological characteristics of poorly responsive subgroups will facilitate the design of novel biologically rational combinations. Novel treatment regimens, including the combination of new drugs with radiation, and the discovery and validation of their associated predictive biomarkers will gradually lead to improved outcomes from therapy.

  5. Nomograms for colorectal cancer: A systematic review

    PubMed Central

    Kawai, Kazushige; Sunami, Eiji; Yamaguchi, Hironori; Ishihara, Soichiro; Kazama, Shinsuke; Nozawa, Hiroaki; Hata, Keisuke; Kiyomatsu, Tomomichi; Tanaka, Junichiro; Tanaka, Toshiaki; Nishikawa, Takeshi; Kitayama, Joji; Watanabe, Toshiaki

    2015-01-01

    AIM: To assist in the selection of suitable nomograms for obtaining desired predictions in daily clinical practice. METHODS: We conducted electronic searches for journal articles on colorectal cancer (CRC)-associated nomograms using the search terms colon/rectal/colorectal/nomogram. Of 174 articles initially found, we retrieved 28 studies in which a nomogram for CRC was developed. RESULTS: We discuss the currently available CRC-associated nomograms, including those that predict the oncological prognosis, the short-term outcome of treatments, such as surgery or neoadjuvant chemoradiotherapy, and the future development of CRC. Developing nomograms always presents a dilemma. On the one hand, the desire to cover as wide a patient range as possible tends to produce nomograms that are too complex and yet have C-indexes that are not sufficiently high. Conversely, confining the target patients might impair the clinical applicability of constructed nomograms. CONCLUSION: The information provided in this review should be of use in selecting a nomogram suitable for obtaining desired predictions in daily clinical practice. PMID:26557011

  6. Computational Identification of Novel Stage-Specific Biomarkers in Colorectal Cancer Progression

    PubMed Central

    Palaniappan, Ashok; Ramar, Karthick; Ramalingam, Satish

    2016-01-01

    It is well-known that the conversion of normal colon epithelium to adenoma and then to carcinoma stems from acquired molecular changes in the genome. The genetic basis of colorectal cancer has been elucidated to a certain extent, and much remains to be known about the identity of specific cancer genes that are associated with the advancement of colorectal cancer from one stage to the next. Here in this study we attempted to identify novel cancer genes that could underlie the stage-specific progression and metastasis of colorectal cancer. We conducted a stage-based meta-analysis of the voluminous tumor genome-sequencing data and mined using multiple approaches for novel genes driving the progression to stage-II, stage-III and stage-IV colorectal cancer. The consensus of these driver genes seeded the construction of stage-specific networks, which were then analyzed for the centrality of genes, clustering of subnetworks, and enrichment of gene-ontology processes. Our study identified three novel driver genes as hubs for stage-II progression: DYNC1H1, GRIN2A, GRM1. Four novel driver genes were identified as hubs for stage-III progression: IGF1R, CPS1, SPTA1, DSP. Three novel driver genes were identified as hubs for stage-IV progression: GSK3B, GGT1, EIF2B5. We also identified several non-driver genes that appeared to underscore the progression of colorectal cancer. Our study yielded potential diagnostic biomarkers for colorectal cancer as well as novel stage-specific drug targets for rational intervention. Our methodology is extendable to the analysis of other types of cancer to fill the gaps in our knowledge. PMID:27243824

  7. Immune reaction and colorectal cancer: Friends or foes?

    PubMed Central

    Formica, Vincenzo; Cereda, Vittore; Nardecchia, Antonella; Tesauro, Manfredi; Roselli, Mario

    2014-01-01

    The potential clinical impact of enhancing antitumor immunity is increasingly recognized in oncology therapeutics for solid tumors. Colorectal cancer is one of the most studied neoplasms for the tumor-host immunity relationship. Although immune cell populations involved in such a relationship and their prognostic role in colorectal cancer development have clearly been identified, still no approved therapies based on host immunity intensification have so far been introduced in clinical practice. Moreover, a recognized risk in enhancing immune reaction for colitis-associated colorectal cancer development has limited the emphasis of this approach. The aim of the present review is to discuss immune components involved in the host immune reaction against colorectal cancer and analyze the fine balance between pro-tumoral and anti-tumoral effect of immunity in this model of disease. PMID:25253941

  8. SATB1 and 2 in colorectal cancer.

    PubMed

    Brocato, Jason; Costa, Max

    2015-02-01

    The special AT-rich sequence-binding proteins 1 and 2 (SATB1/2) are nuclear matrix associated proteins that are transcription factors involved in chromatin remodeling and gene regulation. Expression of the SATB2 gene is tissue-specific, and the only epithelial cells expressing SATB2 are the glandular cells of the lower gastrointestinal tract where its expression is regulated by microRNA-31 (miR-31) and miR-182. SATB2, along with its homolog SATB1, are thought to be involved in various cancers with their roles in this disease being specific to the type of cancer. Colorectal cancer (CRC) provides the largest association of SATB2 with cancer and the roles of SATB2 are better defined and more studied in CRC than in any other cancer type. SATB1 displays a negative association with SATB2 in CRC. The various studies that have investigated the involvement of SATB1 and 2 in CRC have produced consistent findings. Here, we form four major conclusions regarding the role of these proteins in CRC and their potential clinical value: (i) SATB2 is a sensitive marker to distinguish CRC from other cancer types, (ii) Reduced expression of SATB2 in CRC is associated with poor prognosis, (iii) High levels of SATB1 expression facilitate CRC and are associated with poor prognosis and (iv) Overexpression of miR-31 and -182 in CRC leads to more aggressive cancer. This review will describe several of the key investigations that established these conclusions and highlight results that offer opportunities for future research in the treatment and diagnosis of CRC. PMID:25543122

  9. Susceptibility variants for obesity and colorectal cancer risk: the multiethnic cohort and PAGE studies.

    PubMed

    Lim, Unhee; Wilkens, Lynne R; Monroe, Kristine R; Caberto, Christian; Tiirikainen, Maarit; Cheng, Iona; Park, Sungshim Lani; Stram, Daniel O; Henderson, Brian E; Kolonel, Laurence N; Haiman, Christopher A; Le Marchand, Loïc

    2012-09-15

    Obesity is a leading contributor to colorectal cancer risk. We investigated whether the risk variants identified in genome-wide association studies of body mass index (BMI) and waist size are associated with colorectal cancer risk, independently of the effect of obesity phenotype due to a shared etiology. Twenty-four single nucleotide polymorphisms (SNPs) in 15 loci (BDNF, FAIM2, FTO, GNPDA2, KCTD15, LYPLAL1, MC4R, MSRA, MTCH2, NEGR1, NRXN3, SEC16B, SH2B1, TFAP2B and TMEM18) were genotyped in a case-control study of 2,033 colorectal cancer cases and 9,640 controls nested within the multiethnic cohort study, as part of the population architecture using genomics and epidemiology consortium. Risk alleles for two obesity SNPs were associated with colorectal cancer risk--KCTD15 rs29941 [odds ratio (OR) for C allele = 0.90, 95% confidence interval (CI) 0.83-0.98; p = 0.01] and MC4R rs17782313 (OR for C allele = 1.12, 95% CI 1.02-1.22; p = 0.02). These associations were independent of the effect of BMI. However, none of the results remained significant after adjustment for multiple comparisons. No heterogeneity was observed across race/ethnic groups. Our findings suggest that the obesity risk variants are not likely to affect the risk of colorectal cancer substantially.

  10. Examining connections between screening for breast, cervical and prostate cancer and colorectal cancer screening

    PubMed Central

    Wirth, Michael D; Brandt, Heather M; Dolinger, Heather; Hardin, James W; Sharpe, Patricia A; Eberth, Jan M

    2014-01-01

    SUMMARY Aim To compare participation in breast, cervical and prostate cancer screening with colorectal cancer (CRC) screening. Materials & methods This random digit-dialed survey includes participants (aged 50–75 years) from South Carolina (USA). Past participation information in fecal occult blood test, flexible sigmoidoscopy, colonoscopy, mammography, clinical breast examination, Pap test, prostate-specific antigen and digital rectal examination was obtained.Adjusted odds ratios are reported. Results Among European–American women, any cervical or breast cancer screening was associated with adherence to any CRC screening. Among African–American women, mammography was associated with adherence to any CRC screening. Digital rectal examination and prostate-specific antigen tests were associated with adherence to any CRC screening test among all men. Conclusion Future research should explore approaches inclusive of cancer screening recommendations for multiple cancer types for reduction of cancer screening disparities. PMID:25143785

  11. International collaboration for the prevention of colorectal cancer.

    PubMed Central

    Winawer, S. J.

    1990-01-01

    This brief paper describes the involvement of the World Health Organization in promoting international collaboration for the prevention of colorectal cancer, more than half a million cases of which are diagnosed every year. A WHO Collaborating Centre was designated in 1985 in the USA and the activities of this Centre have included the preparation of a series of six articles for publication in the Bulletin of the World Health Organization. These articles deal with primary prevention, risk and screening of average-risk individuals, as well as risk and surveillance of individuals with chronic ulcerative colitis, colorectal polyps, and heritable factors for colorectal cancer. PMID:2393985

  12. [Streamlined treatment pathway for a colorectal cancer patient].

    PubMed

    Rantala, Arto; Ristamäki, Raija; Keränen, Ulla

    2016-01-01

    The organization of colorectal cancer patient treatment, the pathway, is an important component of the quality of care of a large patient group as nearly 3000 colorectal cancer patients are diagnosed and treated annually in Finland. By designing and describing the whole pathway, the more streamlined approach can be made and thus improve patient care. Multidisciplinary team work between colorectal surgeons, oncologists, pathologists and radiologists is flexible team work, having been proven to improve overall treatment results. This method of working together is also a good tool for the development of the pathway to a better organized treatment. PMID:27483633

  13. [Overview of current modalities of colorectal cancer screening].

    PubMed

    Kajzrlíková, Ivana Mikoviny; Vítek, Petr

    2016-04-01

    There are one-step and two-steps programs for colorectal cancer screening. The aim of all screening examinations is to detect early stage of the disease in asymptomatic patient. The aim of this article is actual review of current screening modalities such as fecal occult blood test, flexible sigmoideoscopy, colonoscopy, CT colonography, capsule endoscopy, blood-based tests and stool DNA tests. Colonoscopy still remains the gold standard for detection of colorectal neoplasias. In majority of countries worldwide programs for colorectal cancer screening are based on immunochemical fecal occult blood test followed by colonoscopy when positive.

  14. Familial Colorectal Cancer: Understanding the Alphabet Soup.

    PubMed

    Giglia, Matthew D; Chu, Daniel I

    2016-09-01

    While most colorectal cancers (CRCs) originate from nonhereditary spontaneous mutations, one-third of cases are familial or hereditary. Hereditary CRCs, which account for < 5% of all CRCs, have identifiable germline mutations and phenotypes, such as Lynch syndrome and familial adenomatous polyposis (FAP). Familial CRCs, which account for up to 30% of CRCs, have no identifiable germline mutation or specific pattern of inheritance, but higher-than-expected incidence within a family. Since the discovery that certain genotypes can lead to development of CRC, thousands of mutations have now been implicated in CRC. These new findings have enhanced our ability to identify at-risk patients, initiate better surveillance, and take preventative measures. Given the large number of genes now associated with hereditary and familial CRCs, clinicians should be familiar with the alphabet soup of genes to provide the highest quality of care for patients and families. PMID:27582643

  15. Screening for colorectal cancer: what fits best?

    PubMed

    Lee, Chun Seng; Ronan, Leen; O'Morain, Colm; McNamara, Deirdre

    2012-06-01

    Colorectal cancer (CRC) screening has been shown to be effective in reducing CRC incidence and mortality. There are currently a number of screening modalities available for implementation into a population-based CRC screening program. Each screening method offers different strengths but also possesses its own limitations as a population-based screening strategy. We review the current evidence base for accepted CRC screening tools and evaluate their merits alongside their challenges in fulfilling their role in the detection of CRC. We also aim to provide an outlook on the demands of a low-risk population-based CRC screening program with a view to providing insight as to which modality would best suit current and future needs.

  16. The consensus molecular subtypes of colorectal cancer.

    PubMed

    Guinney, Justin; Dienstmann, Rodrigo; Wang, Xin; de Reyniès, Aurélien; Schlicker, Andreas; Soneson, Charlotte; Marisa, Laetitia; Roepman, Paul; Nyamundanda, Gift; Angelino, Paolo; Bot, Brian M; Morris, Jeffrey S; Simon, Iris M; Gerster, Sarah; Fessler, Evelyn; De Sousa E Melo, Felipe; Missiaglia, Edoardo; Ramay, Hena; Barras, David; Homicsko, Krisztian; Maru, Dipen; Manyam, Ganiraju C; Broom, Bradley; Boige, Valerie; Perez-Villamil, Beatriz; Laderas, Ted; Salazar, Ramon; Gray, Joe W; Hanahan, Douglas; Tabernero, Josep; Bernards, Rene; Friend, Stephen H; Laurent-Puig, Pierre; Medema, Jan Paul; Sadanandam, Anguraj; Wessels, Lodewyk; Delorenzi, Mauro; Kopetz, Scott; Vermeulen, Louis; Tejpar, Sabine

    2015-11-01

    Colorectal cancer (CRC) is a frequently lethal disease with heterogeneous outcomes and drug responses. To resolve inconsistencies among the reported gene expression-based CRC classifications and facilitate clinical translation, we formed an international consortium dedicated to large-scale data sharing and analytics across expert groups. We show marked interconnectivity between six independent classification systems coalescing into four consensus molecular subtypes (CMSs) with distinguishing features: CMS1 (microsatellite instability immune, 14%), hypermutated, microsatellite unstable and strong immune activation; CMS2 (canonical, 37%), epithelial, marked WNT and MYC signaling activation; CMS3 (metabolic, 13%), epithelial and evident metabolic dysregulation; and CMS4 (mesenchymal, 23%), prominent transforming growth factor-β activation, stromal invasion and angiogenesis. Samples with mixed features (13%) possibly represent a transition phenotype or intratumoral heterogeneity. We consider the CMS groups the most robust classification system currently available for CRC-with clear biological interpretability-and the basis for future clinical stratification and subtype-based targeted interventions.

  17. Pharmacologic resistance in colorectal cancer: a review

    PubMed Central

    Hammond, William A.; Swaika, Abhisek; Mody, Kabir

    2016-01-01

    Colorectal cancer (CRC) persists as one of the most prevalent and deadly tumor types in both men and women worldwide. This is in spite of widespread, effective measures of preventive screening, and also major advances in treatment options. Despite advances in cytotoxic and targeted therapy, resistance to chemotherapy remains one of the greatest challenges in long-term management of incurable metastatic disease and eventually contributes to death as tumors accumulate means of evading treatment. We performed a comprehensive literature search on the data available through PubMed, Medline, Scopus, and the ASCO Annual Symposium abstracts through June 2015 for the purpose of this review. We discuss the current state of knowledge of clinically relevant mechanisms of resistance to cytotoxic and targeted therapies now in use for the treatment of CRC. PMID:26753006

  18. [Gastrointestinal oncology: the genetics of colorectal cancer].

    PubMed

    Balaguer Prunés, Francesc

    2011-10-01

    Colorectal cancer (CRC) is one of the most common malignancies in developed countries, and up to 5% of all cases occur in the context of a hereditary syndrome. These hereditary forms often require a high degree of suspicion for diagnosis, as well as specific and specialized management. In addition, a diagnosis of hereditary CRC has major consequences not only for the patient, for whom there are highly effective prevention measures, but also for relatives, who may be carriers of the same condition. The most significant advances in the field of hereditary CRC have occurred in the characterization of serrated polyposis syndrome and in the diagnosis and management of patients with Lynch syndrome and familial adenomatous polyposis.

  19. Estimating the heritability of colorectal cancer

    PubMed Central

    Jiao, Shuo; Peters, Ulrike; Berndt, Sonja; Brenner, Hermann; Butterbach, Katja; Caan, Bette J.; Carlson, Christopher S.; Chan, Andrew T.; Chang-Claude, Jenny; Chanock, Stephen; Curtis, Keith R.; Duggan, David; Gong, Jian; Harrison, Tabitha A.; Hayes, Richard B.; Henderson, Brian E.; Hoffmeister, Michael; Kolonel, Laurence N.; Marchand, Loic Le; Potter, John D.; Rudolph, Anja; Schoen, Robert E.; Seminara, Daniela; Slattery, Martha L.; White, Emily; Hsu, Li

    2014-01-01

    A sizable fraction of colorectal cancer (CRC) is expected to be explained by heritable factors, with heritability estimates ranging from 12 to 35% twin and family studies. Genome-wide association studies (GWAS) have successfully identified a number of common single-nucleotide polymorphisms (SNPs) associated with CRC risk. Although it has been shown that these CRC susceptibility SNPs only explain a small proportion of the genetic risk, it is not clear how much of the heritability these SNPs explain and how much is left to be detected by other, yet to be identified, common SNPs. Therefore, we estimated the heritability of CRC under different scenarios using Genome-Wide Complex Trait Analysis in the Genetics and Epidemiology of Colorectal Cancer Consortium including 8025 cases and 10 814 controls. We estimated that the heritability explained by known common CRC SNPs identified in GWAS was 0.65% (95% CI:0.3–1%; P = 1.11 × 10−16), whereas the heritability explained by all common SNPs was at least 7.42% (95% CI: 4.71–10.12%; P = 8.13 × 10−8), suggesting that many common variants associated with CRC risk remain to be detected. Comparing the heritability explained by the common variants with that from twin and family studies, a fraction of the heritability may be explained by other genetic variants, such as rare variants. In addition, our analysis showed that the gene × smoking interaction explained a significant proportion of the CRC variance (P = 1.26 × 10−2). In summary, our results suggest that known CRC SNPs only explain a small proportion of the heritability and more common SNPs have yet to be identified. PMID:24562164

  20. Systematic genomic identification of colorectal cancer genes delineating advanced from early clinical stage and metastasis

    PubMed Central

    2013-01-01

    Background Colorectal cancer is the third leading cause of cancer deaths in the United States. The initial assessment of colorectal cancer involves clinical staging that takes into account the extent of primary tumor invasion, determining the number of lymph nodes with metastatic cancer and the identification of metastatic sites in other organs. Advanced clinical stage indicates metastatic cancer, either in regional lymph nodes or in distant organs. While the genomic and genetic basis of colorectal cancer has been elucidated to some degree, less is known about the identity of specific cancer genes that are associated with advanced clinical stage and metastasis. Methods We compiled multiple genomic data types (mutations, copy number alterations, gene expression and methylation status) as well as clinical meta-data from The Cancer Genome Atlas (TCGA). We used an elastic-net regularized regression method on the combined genomic data to identify genetic aberrations and their associated cancer genes that are indicators of clinical stage. We ranked candidate genes by their regression coefficient and level of support from multiple assay modalities. Results A fit of the elastic-net regularized regression to 197 samples and integrated analysis of four genomic platforms identified the set of top gene predictors of advanced clinical stage, including: WRN, SYK, DDX5 and ADRA2C. These genetic features were identified robustly in bootstrap resampling analysis. Conclusions We conducted an analysis integrating multiple genomic features including mutations, copy number alterations, gene expression and methylation. This integrated approach in which one considers all of these genomic features performs better than any individual genomic assay. We identified multiple genes that robustly delineate advanced clinical stage, suggesting their possible role in colorectal cancer metastatic progression. PMID:24308539

  1. Can the prognosis of colorectal cancer be improved by surgery?

    PubMed

    Takii, Yasumasa; Maruyama, Satoshi; Nogami, Hitoshi

    2016-08-27

    Surgical resection is the only curative treatment modality for colorectal cancer limited locally. Evidence for the kind of resection procedure that is effective for improving prognosis is insufficient. Prognosis improvement is expected with the no-touch isolation technique (NTIT), making it the most important resection procedure. We are conducting a multicenter randomized controlled trial (RCT) to confirm the efficacy of NTIT in patients with colorectal cancer. The present review serves as a preface to our trial, as it focuses on basic and clinical studies that support the efficacy of NTIT. The detection ratios of circulating tumor cells (CTCs) of peripheral blood indicate the progress and prognosis of colorectal cancer. In a rabbit liver tumor model, metastases increased after surgical manipulation. Also, CTCs increased during the radical excision of colorectal cancer. However, NTIT decreased the detection of CTCs of intraoperative portal vein blood in patients with colorectal cancer. Although these aforementioned results support the use of NTIT, a previous controlled prospective trial was not able to confirm the clinical benefit of NTIT, as it had an insufficient sample size and many patients were lost to follow-up. Therefore, we initiated a large-scale high-quality RCT to confirm the efficacy of NTIT for colorectal cancer. PMID:27648161

  2. Can the prognosis of colorectal cancer be improved by surgery?

    PubMed Central

    Takii, Yasumasa; Maruyama, Satoshi; Nogami, Hitoshi

    2016-01-01

    Surgical resection is the only curative treatment modality for colorectal cancer limited locally. Evidence for the kind of resection procedure that is effective for improving prognosis is insufficient. Prognosis improvement is expected with the no-touch isolation technique (NTIT), making it the most important resection procedure. We are conducting a multicenter randomized controlled trial (RCT) to confirm the efficacy of NTIT in patients with colorectal cancer. The present review serves as a preface to our trial, as it focuses on basic and clinical studies that support the efficacy of NTIT. The detection ratios of circulating tumor cells (CTCs) of peripheral blood indicate the progress and prognosis of colorectal cancer. In a rabbit liver tumor model, metastases increased after surgical manipulation. Also, CTCs increased during the radical excision of colorectal cancer. However, NTIT decreased the detection of CTCs of intraoperative portal vein blood in patients with colorectal cancer. Although these aforementioned results support the use of NTIT, a previous controlled prospective trial was not able to confirm the clinical benefit of NTIT, as it had an insufficient sample size and many patients were lost to follow-up. Therefore, we initiated a large-scale high-quality RCT to confirm the efficacy of NTIT for colorectal cancer.

  3. Detection of colorectal cancer using time-resolved autofluorescence spectrometer

    NASA Astrophysics Data System (ADS)

    Fu, Sheng; Kwek, Leong-Chuan; Chia, Teck-Chee; Lim, Chu-Sing; Tang, Choong-Leong; Ang, Wuan-Suan; Zhou, Miao-Chang; Loke, Po-Ling

    2006-04-01

    As we know Quantum mechanics is a mathematical theory that can describe the behavior of objects that are at microscopic level. Time-resolved autofluorescence spectrometer monitors events that occur during the lifetime of the excited state. This time ranges from a few picoseconds to hundreds of nanoseconds. That is an extremely important advance as it allows environmental parameters to be monitored in a spatially defined manner in the specimen under study. This technique is based on the application of Quantum Mechanics. This principle is applied in our project as we are trying to use different fluorescence spectra to detect biological molecules commonly found in cancerous colorectal tissue and thereby differentiate the cancerous and non-cancerous colorectal polyps more accurately and specifically. In this paper, we use Fluorescence Lifetime Spectrometer (Edinburgh Instruments FL920) to measure decay time of autofluorescence of colorectal cancerous and normal tissue sample. All specimens are from Department of Colorectal Surgery, Singapore General Hospital. The tissues are placed in the time-resolved autofluorescence instrument, which records and calculates the decay time of the autofluorescence in the tissue sample at the excitation and emission wavelengths pre-determined from a conventional spectrometer. By studying the decay time,τ, etc. for cancerous and normal tissue, we aim to present time-resolved autofluorescence as a feasible technique for earlier detection of malignant colorectal tissues. By using this concept, we try to contribute an algorithm even an application tool for real time early diagnosis of colorectal cancer for clinical services.

  4. Coffee Consumption and the Incidence of Colorectal Cancer in Women.

    PubMed

    Groessl, Erik J; Allison, Matthew A; Larson, Joseph C; Ho, Samuel B; Snetslaar, Linda G; Lane, Dorothy S; Tharp, Katie M; Stefanick, Marcia L

    2016-01-01

    Background. Higher coffee consumption has been associated with decreased incidence of colorectal cancer. Our objective was to examine the relationship of coffee intake to colorectal cancer incidence in a large observational cohort of postmenopausal US women. Methods. Data were collected for the Women's Health Initiative Observational Study providing a follow-up period of 12.9 years. The mean age of our sample (N = 83,778 women) was 63.5 years. Daily coffee intake was grouped into 3 categories: None, moderate (>0-<4 cups), and high (4+ cups). Proportional hazards modeling was used to evaluate the relationship between coffee intake and colorectal cancer. Results. There were 1,282 (1.53%) new cases of colorectal cancer during follow-up. Compared to nondrinkers, moderate and high coffee drinkers had an increased incidence of colorectal cancer in multivariate analysis (HR 1.15, 1.02-1.29; HR 1.14, 0.93-1.38). Moderate drip brew coffee intake (HR 1.20, 1.05-1.36) and high nondrip brew coffee intake (HR 1.43, 1.01-2.02) were associated with increased odds. Conclusion. Our results suggesting increased incidence of colorectal cancer associated with higher coffee consumption contradict recent meta-analyses but agree with a number of other studies showing that coffee increases risk or has no effect. Brew method results are novel and warrant further research. PMID:27239197

  5. Preoperative thrombocytosis predicts prognosis in stage II colorectal cancer patients

    PubMed Central

    Lee, Yong Sun; Suh, Kwang Wook

    2016-01-01

    Purpose Thrombocytosis is known to be a poor prognostic factor in several types of solid tumors. The prognostic role of preoperative thrombocytosis in colorectal cancer remains limited. The aim of this study is to investigate the prognostic role of preoperative thrombocytosis in stage II colorectal cancer. Methods Two hundred eighty-four patients with stage II colorectal cancer who underwent surgical resection between December 2003 and December 2009 were retrospectively reviewed. Thrombocytosis was defined as platelet > 450 × 109/L. We compared patients with thrombocytosis and those without thrombocytosis in terms of survival. Results The 5-year disease-free survival (DFS) rates were lower in patients with thrombocytosis compared to those without thrombocytosis in stage II colorectal cancer (73.3% vs. 89.6%, P = 0.021). Cox multivariate analysis demonstrated that thrombocytosis (hazard ratio, 2.945; 95% confidence interval, 1.127–7.697; P = 0.028) was independently associated with DFS in patients with stage II colorectal cancer. Conclusion This study showed that thrombocytosis is a prognostic factor predicting DFS in stage II colorectal cancer patients. PMID:27274508

  6. Can the prognosis of colorectal cancer be improved by surgery?

    PubMed Central

    Takii, Yasumasa; Maruyama, Satoshi; Nogami, Hitoshi

    2016-01-01

    Surgical resection is the only curative treatment modality for colorectal cancer limited locally. Evidence for the kind of resection procedure that is effective for improving prognosis is insufficient. Prognosis improvement is expected with the no-touch isolation technique (NTIT), making it the most important resection procedure. We are conducting a multicenter randomized controlled trial (RCT) to confirm the efficacy of NTIT in patients with colorectal cancer. The present review serves as a preface to our trial, as it focuses on basic and clinical studies that support the efficacy of NTIT. The detection ratios of circulating tumor cells (CTCs) of peripheral blood indicate the progress and prognosis of colorectal cancer. In a rabbit liver tumor model, metastases increased after surgical manipulation. Also, CTCs increased during the radical excision of colorectal cancer. However, NTIT decreased the detection of CTCs of intraoperative portal vein blood in patients with colorectal cancer. Although these aforementioned results support the use of NTIT, a previous controlled prospective trial was not able to confirm the clinical benefit of NTIT, as it had an insufficient sample size and many patients were lost to follow-up. Therefore, we initiated a large-scale high-quality RCT to confirm the efficacy of NTIT for colorectal cancer. PMID:27648161

  7. Coffee Consumption and the Incidence of Colorectal Cancer in Women

    PubMed Central

    Groessl, Erik J.; Allison, Matthew A.; Larson, Joseph C.; Ho, Samuel B.; Snetslaar, Linda G.; Lane, Dorothy S.; Tharp, Katie M.; Stefanick, Marcia L.

    2016-01-01

    Background. Higher coffee consumption has been associated with decreased incidence of colorectal cancer. Our objective was to examine the relationship of coffee intake to colorectal cancer incidence in a large observational cohort of postmenopausal US women. Methods. Data were collected for the Women's Health Initiative Observational Study providing a follow-up period of 12.9 years. The mean age of our sample (N = 83,778 women) was 63.5 years. Daily coffee intake was grouped into 3 categories: None, moderate (>0–<4 cups), and high (4+ cups). Proportional hazards modeling was used to evaluate the relationship between coffee intake and colorectal cancer. Results. There were 1,282 (1.53%) new cases of colorectal cancer during follow-up. Compared to nondrinkers, moderate and high coffee drinkers had an increased incidence of colorectal cancer in multivariate analysis (HR 1.15, 1.02–1.29; HR 1.14, 0.93–1.38). Moderate drip brew coffee intake (HR 1.20, 1.05–1.36) and high nondrip brew coffee intake (HR 1.43, 1.01–2.02) were associated with increased odds. Conclusion. Our results suggesting increased incidence of colorectal cancer associated with higher coffee consumption contradict recent meta-analyses but agree with a number of other studies showing that coffee increases risk or has no effect. Brew method results are novel and warrant further research. PMID:27239197

  8. Enhancing knowledge of colorectal cancer among African Americans: why are we waiting until age 50?

    PubMed

    Powe, Barbara D; Finnie, Ramona; Ko, Jean

    2006-01-01

    Because of low rates of colorectal cancer screening among African Americans, it may be beneficial to begin educating persons about this disease before age 50. Using the Patient/Provider/System Theoretical Model for cancer screening, this study compared knowledge of colorectal cancer, sources of information, and awareness of programs among participants of age 20-29, 30-49, and 50-75 years. The majority (n = 354) were women and African American (mean age = 37 years, mean education = 12th grade). Younger participants tended to know less about the disease, but there were few differences in knowledge between the two older groups. Persons in the 40-49-year age group were more likely to be familiar with the role diet plays in the risk of colorectal cancer. Participants associated the need for screening with the presence of symptoms. Television and radio were listed as the most frequent source of information about cancer. The Internet was the least used. The majority were not familiar with selected national programs and services focused on increasing awareness of cancer. Findings suggest that colorectal cancer-related information should be targeted toward this population before age 50, using multiple sources such as TV/radio, providers, magazines, and cancer-related organizations. An estimated 104,950 colon and 40,340 rectal cancer cases will be diagnosed in 2005 with an estimated 56,290 deaths from the disease (American Cancer Society [ACS], 2005). Despite a stabilization of colorectal cancer (CRC) incidence rates since the 1980s, African American males and females have higher incidence and mortality rates associated with this disease compared to Whites. The 5-year survival rate for CRC among African Americans improved to 54% during the years 1995-2000, but lagged well behind the 64% survival rate for Whites during the same time period. Screening and early detection of CRC followed by effective treatment is crucial to reducing these mortality rates.

  9. Coffee, colon function and colorectal cancer.

    PubMed

    Vitaglione, Paola; Fogliano, Vincenzo; Pellegrini, Nicoletta

    2012-09-01

    For several years the physiological effects of coffee have been focused on its caffeine content, disregarding the hundreds of bioactive coffee components, such as polyphenols, melanoidins, carbohydrates, diterpenes, etc. These compounds may exert their protection against colorectal cancer (CRC), the third most common cancer worldwide. However, the amount and type of compounds ingested with the beverage may be highly different depending on the variety of coffee used, the roasting degree, the type of brewing method as well as the serving size. In this frame, this paper reviews the mechanisms by which coffee may influence the risk of CRC development focusing on espresso and filtered coffee, as well as on the components that totally or partially reach the colon i.e. polyphenols and dietary fiber, including melanoidins. In particular the effects of coffee on some colon conditions whose deregulation may lead to cancer, namely microbiota composition and lumen reducing environment, were considered. Taken together the discussed studies indicated that, due to their in vivo metabolism and composition, both coffee chlorogenic acids and dietary fiber, including melanoidins, may reduce CRC risk, increasing colon motility and antioxidant status. Further studies should finally assess whether the coffee benefits for colon are driven through a prebiotic effect.

  10. Cytokine-Induced Modulation of Colorectal Cancer

    PubMed Central

    Mager, Lukas F.; Wasmer, Marie-Hélène; Rau, Tilman T.; Krebs, Philippe

    2016-01-01

    The emergence of novel immunomodulatory cancer therapies over the last decade, above all immune checkpoint blockade, has significantly advanced tumor treatment. For colorectal cancer (CRC), a novel scoring system based on the immune cell infiltration in tumors has greatly improved disease prognostic evaluation and guidance to more specific therapy. These findings underline the relevance of tumor immunology in the future handling and therapeutic approach of malignant disease. Inflammation can either promote or suppress CRC pathogenesis and inflammatory mediators, mainly cytokines, critically determine the pro- or anti-tumorigenic signals within the tumor environment. Here, we review the current knowledge on the cytokines known to be critically involved in CRC development and illustrate their mechanisms of action. We also highlight similarities and differences between CRC patients and murine models of CRC and point out cytokines with an ambivalent role for intestinal cancer. We also identify some of the future challenges in the field that should be addressed for the development of more effective immunomodulatory therapies. PMID:27148488

  11. Aspirin, cyclooxygenase inhibition and colorectal cancer

    PubMed Central

    Sostres, Carlos; Gargallo, Carla Jerusalen; Lanas, Angel

    2014-01-01

    Colorectal cancer (CRC) is the third most common type of cancer worldwide. Screening measures are far from adequate and not widely available in resource-poor settings. Primary prevention strategies therefore remain necessary to reduce the risk of developing CRC. Increasing evidence from epidemiological studies, randomized clinical trials and basic science supports the effectiveness of aspirin, as well as other non-steroidal anti-inflammatory drugs, for chemoprevention of several types of cancer, including CRC. This includes the prevention of adenoma recurrence and reduction of CRC incidence and mortality. The detectable benefit of daily low-dose aspirin (at least 75 mg), as used to prevent cardiovascular disease events, strongly suggests that its antiplatelet action is central to explaining its antitumor efficacy. Daily low-dose aspirin achieves complete and persistent inhibition of cyclooxygenase (COX)-1 in platelets (in pre-systemic circulation) while causing a limited and rapidly reversible inhibitory effect on COX-2 and/or COX-1 expressed in nucleated cells. Aspirin has a short half-life in human circulation (about 20 minutes); nucleated cells have the ability to resynthesize acetylated COX isozymes within a few hours, while platelets do not. COX-independent mechanisms of aspirin have been suggested to explain its chemopreventive effects but this concept remains to be demonstrated in vivo at clinical doses. PMID:24605250

  12. Aspirin, cyclooxygenase inhibition and colorectal cancer.

    PubMed

    Sostres, Carlos; Gargallo, Carla Jerusalen; Lanas, Angel

    2014-02-01

    Colorectal cancer (CRC) is the third most common type of cancer worldwide. Screening measures are far from adequate and not widely available in resource-poor settings. Primary prevention strategies therefore remain necessary to reduce the risk of developing CRC. Increasing evidence from epidemiological studies, randomized clinical trials and basic science supports the effectiveness of aspirin, as well as other non-steroidal anti-inflammatory drugs, for chemoprevention of several types of cancer, including CRC. This includes the prevention of adenoma recurrence and reduction of CRC incidence and mortality. The detectable benefit of daily low-dose aspirin (at least 75 mg), as used to prevent cardiovascular disease events, strongly suggests that its antiplatelet action is central to explaining its antitumor efficacy. Daily low-dose aspirin achieves complete and persistent inhibition of cyclooxygenase (COX)-1 in platelets (in pre-systemic circulation) while causing a limited and rapidly reversible inhibitory effect on COX-2 and/or COX-1 expressed in nucleated cells. Aspirin has a short half-life in human circulation (about 20 minutes); nucleated cells have the ability to resynthesize acetylated COX isozymes within a few hours, while platelets do not. COX-independent mechanisms of aspirin have been suggested to explain its chemopreventive effects but this concept remains to be demonstrated in vivo at clinical doses.

  13. Cytokine-Induced Modulation of Colorectal Cancer.

    PubMed

    Mager, Lukas F; Wasmer, Marie-Hélène; Rau, Tilman T; Krebs, Philippe

    2016-01-01

    The emergence of novel immunomodulatory cancer therapies over the last decade, above all immune checkpoint blockade, has significantly advanced tumor treatment. For colorectal cancer (CRC), a novel scoring system based on the immune cell infiltration in tumors has greatly improved disease prognostic evaluation and guidance to more specific therapy. These findings underline the relevance of tumor immunology in the future handling and therapeutic approach of malignant disease. Inflammation can either promote or suppress CRC pathogenesis and inflammatory mediators, mainly cytokines, critically determine the pro- or anti-tumorigenic signals within the tumor environment. Here, we review the current knowledge on the cytokines known to be critically involved in CRC development and illustrate their mechanisms of action. We also highlight similarities and differences between CRC patients and murine models of CRC and point out cytokines with an ambivalent role for intestinal cancer. We also identify some of the future challenges in the field that should be addressed for the development of more effective immunomodulatory therapies.

  14. Genetic variability in EGFR, Src and HER2 and risk of colorectal adenoma and cancer

    PubMed Central

    Poole, Elizabeth M; Curtin, Karen; Hsu, Li; Kulmacz, Richard J; Duggan, David J; Makar, Karen W; Xiao, Liren; Carlson, Christopher S; Slattery, Martha L; Caan, Bette J; Potter, John D; Ulrich, Cornelia M

    2011-01-01

    The EGFR signaling pathway is involved in carcinogenesis at multiple sites, particularly colorectal cancer, and is a target of colorectal cancer chemotherapy. EGFR signaling is linked to pro-carcinogenic mechanisms, including cell proliferation, survival, angiogenesis, and more recently prostaglandin synthesis. Genetic variability in this pathway has not yet been studied in relation to colorectal carcinogenesis. In three case-control studies of colorectal adenoma (n=485 cases/578 controls), colon cancer (n=1424 cases/1780 controls) and rectal cancer (n=583 cases/775 controls), we investigated associations between candidate SNPs, tagSNPs and haplotypes in EGFR signaling (EGFR, Src, and HER2) and risk. We also examined associations with tumor subtypes: TP53 and KRAS2 mutations, CpG island methylator phenotype, and microsatellite instability. All three studies were genotyped using an identical Illumina GoldenGate assay, allowing thorough investigation of genetic variability across stages and locations of colorectal neoplasia. The EGFR tagSNP 142572T>C (rs3752651) CC genotype was associated with a suggested increased risk for both colon (OR: 1.40; 95% CI: 1.00-1.96; p-trend=0.04) and rectal cancer (OR: 1.39; 95% CI: 0.81-2.41; p-trend=0.65). In tumor subtype analyses, the association was limited to TP53-mutated colon tumors. Using the Chatterjee 1 df Tukey test to assess gene-gene interactions, we observed a statistically significant (p<0.01) interaction between SNPs in EGFR and Src for colorectal adenoma risk. The association with EGFR 142572 should be investigated in additional studies and the significant gene-gene interaction between EGFR and Src in relation to adenoma risk suggests that these two genes are jointly affecting early stages in colorectal carcinogenesis and requires further follow-up. PMID:22199994

  15. Growth suppression of colorectal cancer by plant-derived multiple mAb CO17-1A × BR55 via inhibition of ERK1/2 phosphorylation.

    PubMed

    Kwak, Dong Hoon; Moussavou, Ghislain; Lee, Ju Hyoung; Heo, Sung Youn; Ko, Kisung; Hwang, Kyung-A; Jekal, Seung-Joo; Choo, Young-Kug

    2014-01-01

    We have generated the transgenic Tabaco plants expressing multiple monoclonal antibody (mAb) CO7-1A × BR55 by cross-pollinating with mAb CO17-1A and mAb BR55. We have demonstrated the anti-cancer effect of plant-derived multiple mAb CO17-1A × BR55. We find that co-treatment of colorectal mAbs (anti-epithelial cellular adhesion molecule (EpCAM), plant-derived monoclonal antibody (mAb(P)) CO17-1A and mAb(P) CO17-1A × BR55) with RAW264.7 cells significantly inhibited the cell growth in SW620 cancer cells. In particular, multi mAb(P) CO17-1A × BR55 significantly and efficiently suppressed the growth of SW620 cancer cells compared to another mAbs. Apoptotic death-positive cells were significantly increased in the mAb(P) CO17-1A × BR55-treated. The mAb(P) CO17-1A × BR55 treatment significantly decreased the expression of B-Cell lymphoma-2 (BCl-2), but the expression of Bcl-2-associated X protein (Bax), and cleaved caspase-3 were markedly increased. In vivo, the mAb(P) CO17-1A × BR55 significantly and efficiently inhibited the growth of colon tumors compared to another mAbs. The apoptotic cell death and inhibition of pro-apoptotic proteins expression were highest by treatment with mAb(P) CO17-1A × BR55. In addition, the mAb(P) CO17-1A × BR55 significantly inhibited the extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation in cancer cells and tumors. Therefore, this study results suggest that multiple mAb(P) CO17-1A × BR55 has a significant effect on apoptosis-mediated anticancer by suppression of ERK1/2 phosphorylation in colon cancer compared to another mAbs. In light of these results, further clinical investigation should be conducted on mAb(P) CO17-1A × BR55 to determine its possible chemopreventive and/or therapeutic efficacy against human colon cancer. PMID:25405740

  16. Growth suppression of colorectal cancer by plant-derived multiple mAb CO17-1A × BR55 via inhibition of ERK1/2 phosphorylation.

    PubMed

    Kwak, Dong Hoon; Moussavou, Ghislain; Lee, Ju Hyoung; Heo, Sung Youn; Ko, Kisung; Hwang, Kyung-A; Jekal, Seung-Joo; Choo, Young-Kug

    2014-11-14

    We have generated the transgenic Tabaco plants expressing multiple monoclonal antibody (mAb) CO7-1A × BR55 by cross-pollinating with mAb CO17-1A and mAb BR55. We have demonstrated the anti-cancer effect of plant-derived multiple mAb CO17-1A × BR55. We find that co-treatment of colorectal mAbs (anti-epithelial cellular adhesion molecule (EpCAM), plant-derived monoclonal antibody (mAb(P)) CO17-1A and mAb(P) CO17-1A × BR55) with RAW264.7 cells significantly inhibited the cell growth in SW620 cancer cells. In particular, multi mAb(P) CO17-1A × BR55 significantly and efficiently suppressed the growth of SW620 cancer cells compared to another mAbs. Apoptotic death-positive cells were significantly increased in the mAb(P) CO17-1A × BR55-treated. The mAb(P) CO17-1A × BR55 treatment significantly decreased the expression of B-Cell lymphoma-2 (BCl-2), but the expression of Bcl-2-associated X protein (Bax), and cleaved caspase-3 were markedly increased. In vivo, the mAb(P) CO17-1A × BR55 significantly and efficiently inhibited the growth of colon tumors compared to another mAbs. The apoptotic cell death and inhibition of pro-apoptotic proteins expression were highest by treatment with mAb(P) CO17-1A × BR55. In addition, the mAb(P) CO17-1A × BR55 significantly inhibited the extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation in cancer cells and tumors. Therefore, this study results suggest that multiple mAb(P) CO17-1A × BR55 has a significant effect on apoptosis-mediated anticancer by suppression of ERK1/2 phosphorylation in colon cancer compared to another mAbs. In light of these results, further clinical investigation should be conducted on mAb(P) CO17-1A × BR55 to determine its possible chemopreventive and/or therapeutic efficacy against human colon cancer.

  17. Growth Suppression of Colorectal Cancer by Plant-Derived Multiple mAb CO17-1A × BR55 via Inhibition of ERK1/2 Phosphorylation

    PubMed Central

    Kwak, Dong Hoon; Moussavou, Ghislain; Lee, Ju Hyoung; Heo, Sung Youn; Ko, Kisung; Hwang, Kyung-A; Jekal, Seung-Joo; Choo, Young-Kug

    2014-01-01

    We have generated the transgenic Tabaco plants expressing multiple monoclonal antibody (mAb) CO7-1A × BR55 by cross-pollinating with mAb CO17-1A and mAb BR55. We have demonstrated the anti-cancer effect of plant-derived multiple mAb CO17-1A × BR55. We find that co-treatment of colorectal mAbs (anti-epithelial cellular adhesion molecule (EpCAM), plant-derived monoclonal antibody (mAbP) CO17-1A and mAbP CO17-1A × BR55) with RAW264.7 cells significantly inhibited the cell growth in SW620 cancer cells. In particular, multi mAbP CO17-1A × BR55 significantly and efficiently suppressed the growth of SW620 cancer cells compared to another mAbs. Apoptotic death-positive cells were significantly increased in the mAbP CO17-1A × BR55-treated. The mAbP CO17-1A × BR55 treatment significantly decreased the expression of B-Cell lymphoma-2 (BCl-2), but the expression of Bcl-2-associated X protein (Bax), and cleaved caspase-3 were markedly increased. In vivo, the mAbP CO17-1A × BR55 significantly and efficiently inhibited the growth of colon tumors compared to another mAbs. The apoptotic cell death and inhibition of pro-apoptotic proteins expression were highest by treatment with mAbP CO17-1A × BR55. In addition, the mAbP CO17-1A × BR55 significantly inhibited the extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation in cancer cells and tumors. Therefore, this study results suggest that multiple mAbP CO17-1A × BR55 has a significant effect on apoptosis-mediated anticancer by suppression of ERK1/2 phosphorylation in colon cancer compared to another mAbs. In light of these results, further clinical investigation should be conducted on mAbP CO17-1A × BR55 to determine its possible chemopreventive and/or therapeutic efficacy against human colon cancer. PMID:25405740

  18. Colorectal (Colon) Cancer: What Are the Risk Factors?

    MedlinePlus

    ... What Are the Risk Factors for Colorectal Cancer? Language: English Español (Spanish) Recommend on Facebook Tweet Share Compartir ... Cancer Institute) Learning About Colon Cancer Stay Informed Language: English Español (Spanish) File Formats Help: How do I ...

  19. Colorectal cancer: from prevention to personalized medicine.

    PubMed

    Binefa, Gemma; Rodríguez-Moranta, Francisco; Teule, Alex; Medina-Hayas, Manuel

    2014-06-14

    Colorectal cancer (CRC) is a very heterogeneous disease that is caused by the interaction of genetic and environmental factors. CRC develops through a gradual accumulation of genetic and epigenetic changes, leading to the transformation of normal colonic mucosa into invasive cancer. CRC is one of the most prevalent and incident cancers worldwide, as well as one of the most deadly. Approximately 1235108 people are diagnosed annually with CRC, and 609051 die from CRC annually. The World Health Organization estimates an increase of 77% in the number of newly diagnosed cases of CRC and an increase of 80% in deaths from CRC by 2030. The incidence of CRC can benefit from different strategies depending on its stage: health promotion through health education campaigns (when the disease is not yet present), the implementation of screening programs (for detection of the disease in its early stages), and the development of nearly personalized treatments according to both patient characteristics (age, sex) and the cancer itself (gene expression). Although there are different strategies for screening and although the number of such strategies is increasing due to the potential of emerging technologies in molecular marker application, not all strategies meet the criteria required for screening tests in population programs; the three most accepted tests are the fecal occult blood test (FOBT), colonoscopy and sigmoidoscopy. FOBT is the most used method for CRC screening worldwide and is also the primary choice in most population-based screening programs in Europe. Due to its non-invasive nature and low cost, it is one of the most accepted techniques by population. CRC is a very heterogeneous disease, and with a few exceptions (APC, p53, KRAS), most of the genes involved in CRC are observed in a small percentage of cases. The design of genetic and epigenetic marker panels that are able to provide maximum coverage in the diagnosis of colorectal neoplasia seems a reasonable strategy

  20. Colorectal cancer: From prevention to personalized medicine

    PubMed Central

    Binefa, Gemma; Rodríguez-Moranta, Francisco; Teule, Àlex; Medina-Hayas, Manuel

    2014-01-01

    Colorectal cancer (CRC) is a very heterogeneous disease that is caused by the interaction of genetic and environmental factors. CRC develops through a gradual accumulation of genetic and epigenetic changes, leading to the transformation of normal colonic mucosa into invasive cancer. CRC is one of the most prevalent and incident cancers worldwide, as well as one of the most deadly. Approximately 1235108 people are diagnosed annually with CRC, and 609051 die from CRC annually. The World Health Organization estimates an increase of 77% in the number of newly diagnosed cases of CRC and an increase of 80% in deaths from CRC by 2030. The incidence of CRC can benefit from different strategies depending on its stage: health promotion through health education campaigns (when the disease is not yet present), the implementation of screening programs (for detection of the disease in its early stages), and the development of nearly personalized treatments according to both patient characteristics (age, sex) and the cancer itself (gene expression). Although there are different strategies for screening and although the number of such strategies is increasing due to the potential of emerging technologies in molecular marker application, not all strategies meet the criteria required for screening tests in population programs; the three most accepted tests are the fecal occult blood test (FOBT), colonoscopy and sigmoidoscopy. FOBT is the most used method for CRC screening worldwide and is also the primary choice in most population-based screening programs in Europe. Due to its non-invasive nature and low cost, it is one of the most accepted techniques by population. CRC is a very heterogeneous disease, and with a few exceptions (APC, p53, KRAS), most of the genes involved in CRC are observed in a small percentage of cases. The design of genetic and epigenetic marker panels that are able to provide maximum coverage in the diagnosis of colorectal neoplasia seems a reasonable strategy

  1. Pharmacological and dietary prevention for colorectal cancer

    PubMed Central

    2013-01-01

    Background Colorectal cancer (CRC) is a leading cause of cancer morbidity and mortality. People at higher risk are those individuals with a family history of CRC and familial adenomatous polyposis. Prevention and screening are two milestones for this disease. The aim of this study is to evaluate the chemopreventive role of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin and cyclooxygenase 2 inhibitors, some micronutrients (folic acid, calcium, selenium, antioxidants) and probiotics. Discussion The studies on aspiring reported promising results, but it is debatable whether aspirin should be used as chemoprevention, because of its side effects and because of poor efficacy evident in subjects at high risk. Similar results were reported for other non-aspirin NSAIDs, such as sulindac and celecoxib, which the potential adverse effects limit their use. Selenium role in prevention of various types of cancer as well as in colon adenomas are often inconclusive or controversial. Several studies suggested that calcium may have a possible chemopreventive effect on colon adenomas and CRC, although contrasting results are reported for the latter. A recent meta-analysis including 13 randomized trial suggested that folic acid supplementation had not a chemiopreventive action on CRC. Several studies investigated the association between antioxidants, administered alone or in combination, and CRC risk, both among general and at risk population, but only few of them supported statistically significant results. Conclusion The results of this literature review showed an unclear role in CRC prevention of both pharmacological and dietary intervention. Despite several options are available to prevent colon cancer, it is challenging to identify a correct strategy to prevent CRC through pharmacological and dietary intervention due to the long latency of cancer promotion and development. Since some of the drugs investigated may have uncertain individual effects, it can be

  2. Multiple Primary Cancer Monograph

    Cancer.gov

    To identify groups of cancer survivors that are at increased risk for multiple primary cancers, investigators led an effort to provide the first comprehensive population-based analysis of the risk of subsequent cancer in the U.S., resulting in a monograph.

  3. Human Blood Autoantibodies in the Detection of Colorectal Cancer.

    PubMed

    Negm, Ola H; Hamed, Mohamed R; Schoen, Robert E; Whelan, Richard L; Steele, Robert J; Scholefield, John; Dilnot, Elizabeth M; Shantha Kumara, H M C; Robertson, John F R; Sewell, Herbert F

    2016-01-01

    Colorectal cancer (CRC) is the second most common malignancy in the western world. Early detection and diagnosis of all cancer types is vital to improved prognosis by enabling early treatment when tumours should be both resectable and curable. Sera from 3 different cohorts; 42 sera (21 CRC and 21 matched controls) from New York, USA, 200 sera from Pittsburgh, USA (100 CRC and 100 controls) and 20 sera from Dundee, UK (10 CRC and 10 controls) were tested against a panel of multiple tumour-associated antigens (TAAs) using an optimised multiplex microarray system. TAA specific IgG responses were interpolated against the internal IgG standard curve for each sample. Individual TAA specific responses were examined in each cohort to determine cutoffs for a robust initial scoring method to establish sensitivity and specificity. Sensitivity and specificity of combinations of TAAs provided good discrimination between cancer-positive and normal serum. The overall sensitivity and specificity of the sample sets tested against a panel of 32 TAAs were 61.1% and 80.9% respectively for 6 antigens; p53, AFP, K RAS, Annexin, RAF1 and NY-CO16. Furthermore, the observed sensitivity in Pittsburgh sample set in different clinical stages of CRC; stage I (n = 19), stage II (n = 40), stage III (n = 34) and stage IV (n = 6) was similar (73.6%, 75.0%, 73.5% and 83.3%, respectively), with similar levels of sensitivity for right and left sided CRC. We identified an antigen panel of sufficient sensitivity and specificity for early detection of CRC, based upon serum profiling of autoantibody response using a robust multiplex antigen microarray technology. This opens the possibility of a blood test for screening and detection of early colorectal cancer. However this panel will require further validation studies before they can be proposed for clinical practice. PMID:27383396

  4. Human Blood Autoantibodies in the Detection of Colorectal Cancer

    PubMed Central

    Negm, Ola H.; Hamed, Mohamed R.; Schoen, Robert E.; Whelan, Richard L.; Steele, Robert J.; Scholefield, John; Dilnot, Elizabeth M.; Shantha Kumara, H. M. C.; Robertson, John F. R.; Sewell, Herbert F.

    2016-01-01

    Colorectal cancer (CRC) is the second most common malignancy in the western world. Early detection and diagnosis of all cancer types is vital to improved prognosis by enabling early treatment when tumours should be both resectable and curable. Sera from 3 different cohorts; 42 sera (21 CRC and 21 matched controls) from New York, USA, 200 sera from Pittsburgh, USA (100 CRC and 100 controls) and 20 sera from Dundee, UK (10 CRC and 10 controls) were tested against a panel of multiple tumour-associated antigens (TAAs) using an optimised multiplex microarray system. TAA specific IgG responses were interpolated against the internal IgG standard curve for each sample. Individual TAA specific responses were examined in each cohort to determine cutoffs for a robust initial scoring method to establish sensitivity and specificity. Sensitivity and specificity of combinations of TAAs provided good discrimination between cancer-positive and normal serum. The overall sensitivity and specificity of the sample sets tested against a panel of 32 TAAs were 61.1% and 80.9% respectively for 6 antigens; p53, AFP, K RAS, Annexin, RAF1 and NY-CO16. Furthermore, the observed sensitivity in Pittsburgh sample set in different clinical stages of CRC; stage I (n = 19), stage II (n = 40), stage III (n = 34) and stage IV (n = 6) was similar (73.6%, 75.0%, 73.5% and 83.3%, respectively), with similar levels of sensitivity for right and left sided CRC. We identified an antigen panel of sufficient sensitivity and specificity for early detection of CRC, based upon serum profiling of autoantibody response using a robust multiplex antigen microarray technology. This opens the possibility of a blood test for screening and detection of early colorectal cancer. However this panel will require further validation studies before they can be proposed for clinical practice. PMID:27383396

  5. Wnt/β-catenin signaling regulated SATB1 promotes colorectal cancer tumorigenesis and progression.

    PubMed

    Mir, R; Pradhan, S J; Patil, P; Mulherkar, R; Galande, S

    2016-03-31

    The chromatin organizer SATB1 has been implicated in the development and progression of multiple cancers including breast and colorectal cancers. However, the regulation and role of SATB1 in colorectal cancers is poorly understood. Here, we demonstrate that expression of SATB1 is induced upon hyperactivation of Wnt/β-catenin signaling and repressed upon depletion of TCF7L2 (TCF4) and β-catenin. Using several colorectal cancer cell line models and the APC min mutant zebrafish in vivo model, we established that SATB1 is a novel target of Wnt/β-catenin signaling. We show that direct binding of TCF7L2/β-catenin complex on Satb1 promoter is required for the regulation of SATB1. Moreover, SATB1 is sufficient to regulate the expression of β-catenin, members of TCF family, multiple downstream effectors and mediators of Wnt pathway. SATB1 potentiates the cellular changes and expression of key cancer-associated genes in non-aggressive colorectal cells, promotes their aggressive phenotype and tumorigenesis in vivo. Conversely, depletion of SATB1 from aggressive cells reprograms the expression of cancer-associated genes, reverses their cancer phenotype and reduces the potential of these cells to develop tumors in vivo. We also show that SATB1 and β-catenin bind to the promoters of TCF7L2 and the downstream targets of Wnt signaling and regulate their expression. Our findings suggest that SATB1 shares a feedback regulatory network with TCF7L2/β-catenin signaling and is required for Wnt signaling-dependent regulation of β-catenin. Collectively, these results provide unequivocal evidence to establish that SATB1 reprograms the expression of tumor growth- and metastasis-associated genes to promote tumorigenesis and functionally overlaps with Wnt signaling critical for colorectal cancer tumorigenesis.

  6. The expression and correlation of SIRT1 and Phospho-SIRT1 in colorectal cancer.

    PubMed

    Zhang, Xianzhen; Chen, Suiqin; Cheng, Meili; Cao, Fangli; Cheng, Yufeng

    2015-01-01

    SIRT1 is the homologue of sir2 in mammals, which is a nicotinamide adenine dinucleotide (NAD(+)) dependent histone deacetylase. SIRT1 is involved in many physiological processes, such as metabolism, senescence, inflammatory response, neuroprotection, and tumorigenesis by acetylating histones and multiple transcription factors. However, the exact role of SIRT1 in tumor is still under controversial. Immunohistochemistry and Western blot were performed to investigate the expressions and subcellular localizations of SIRT1 and Phospho-SIRT1 in colorectal cancer tissues and adjacent normal tissues. The relationship between SIRT1 or Phospho-SIRT1 and clinicopathological characteristics was also analyzed. Real-Time PCR was performed to investigate the transcriptional level of SIRT1 mRNA in colorectal cancer tissues and adjacent normal tissues. SIRT1 and Phospho-SIRT1 were both localized in the nucleus. The expressions of SIRT1 and Phospho-SIRT1 were higher in colorectal cancer tissues than normal tissues. SIRT1 expression in cancer tissues was associated with patient age, TNM stage and mutant P53 loss. Phospho-SIRT1 expression in cancer tissues was associated with Ki67. SIRT1 and Phospho-SIRT1 were highly correlated in cancer tissues and normal tissues. The ratios of Phospho-SIRT1 and SIRT1 expression in cancer tissues were higher than normal tissues. SIRT1 mRNA level was no significant difference in cancer tissues and normal tissues. SIRT1 have a dual character in colorectal cancer, and Phospho-SIRT1 may determine the role of SIRT1 in colorectal cancer formation. PMID:25785061

  7. crcTRP: A Translational Research Platform for Colorectal Cancer

    PubMed Central

    Deng, Ning; Zheng, Ling; Liu, Fang; Wang, Li; Duan, Huilong

    2013-01-01

    Colorectal cancer is a leading cause of cancer mortality in both developed and developing countries. Transforming basic research results into clinical practice is one of the key tasks of translational research, which will greatly improve the diagnosis and treatments of colorectal cancer. In this paper, a translational research platform for colorectal cancer, named crcTRP, is introduced. crcTRP serves the colorectal cancer translational research by providing various types of biomedical information related with colorectal cancer to the community. The information, including clinical data, epidemiology data, individual omics data, and public omics data, was collected through a multisource biomedical information collection solution and then integrated in a clinic-omics database, which was constructed with EAV-ER model for flexibility and efficiency. A preliminary exploration of conducting translational research on crcTRP was implemented and worked out a set of clinic-genomic relations, linking clinical data with genomic data. These relations have also been applied to crcTRP to make it more conductive for cancer translational research. PMID:23431356

  8. Motivational Interviewing and Colorectal Cancer Screening

    PubMed Central

    Wahab, Stéphanie; Menon, Usha; Szalacha, Laura

    2008-01-01

    Objective This article focuses on design, training, and delivery of MI in a longitudinal randomized controlled trial intended to assess the efficacy of two separate interventions designed to increase colorectal screening when compared to a usual care, control group. One intervention was a single-session, telephone-based motivational interview (MI), created to increase colorectal cancer screening within primary care populations. The other was tailored health counseling. We present the rationale, design, and process discussions of the one-time motivational interview telephone intervention. We discuss in this paper the training and supervision of study interventionists, in order to enhance practice and research knowledge concerned with fidelity issues in motivational interview interventions. Methods To improve motivational interview proficiency and effectiveness, we developed a prescribed training program adapting MI to a telephone counseling session. Results The four interventionists trained in MI demonstrate some MI proficiency assessed by the Motivational Interviewing Treatment Integrity Scale. In the post-intervention interview, 20.5% of the MI participants reported having had a CRC screening test, and another 19.75% (n = 16) had scheduled a screening test. Almost half of the participants (43%) indicated that the phone conversation helped them to overcome the reasons why they had not had a screening test. Conclusions Ongoing supervision and training (post MI workshop) are crucial to supporting MI fidelity. The trajectory of learning MI demonstrated by the interventionists is consistent with the eight stages of learning MI. The MI roadmap created for the interventionists has shown to be more of a distraction than a facilitator in the delivery of the telephone intervention. MI can, however, be considered a useful tool for health education and warrants further study. Practice Implications MI training should include consistent training and process evaluation. MI can

  9. Minimally Invasive Colorectal Cancer Surgery in Europe

    PubMed Central

    Babaei, Masoud; Balavarca, Yesilda; Jansen, Lina; Gondos, Adam; Lemmens, Valery; Sjövall, Annika; B⊘rge Johannesen, Tom; Moreau, Michel; Gabriel, Liberale; Gonçalves, Ana Filipa; Bento, Maria José; van de Velde, Tony; Kempfer, Lana Raffaela; Becker, Nikolaus; Ulrich, Alexis; Ulrich, Cornelia M.; Schrotz-King, Petra; Brenner, Hermann

    2016-01-01

    Abstract Minimally invasive surgery (MIS) of colorectal cancer (CRC) was first introduced over 20 years ago and recently has gained increasing acceptance and usage beyond clinical trials. However, data on dissemination of the method across countries and on long-term outcomes are still sparse. In the context of a European collaborative study, a total of 112,023 CRC cases from 3 population-based (N = 109,695) and 4 institute-based clinical cancer registries (N = 2328) were studied and compared on the utilization of MIS versus open surgery. Cox regression models were applied to study associations between surgery type and survival of patients from the population-based registries. The study considered adjustment for potential confounders. The percentage of CRC patients undergoing MIS differed substantially between centers and generally increased over time. MIS was significantly less often used in stage II to IV colon cancer compared with stage I in most centers. MIS tended to be less often used in older (70+) than in younger colon cancer patients. MIS tended to be more often used in women than in men with rectal cancer. MIS was associated with significantly reduced mortality among colon cancer patients in the Netherlands (hazard ratio [HR] 0.66, 95% confidence interval [CI] (0.63–0.69), Sweden (HR 0.68, 95% CI 0.60–0.76), and Norway (HR 0.73, 95% CI 0.67–0.79). Likewise, MIS was associated with reduced mortality of rectal cancer patients in the Netherlands (HR 0.74, 95% CI 0.68–0.80) and Sweden (HR 0.77, 95% CI 0.66–0.90). Utilization of MIS in CRC resection is increasing, but large variation between European countries and clinical centers prevails. Our results support association of MIS with substantially enhanced survival among colon cancer patients. Further studies controlling for selection bias and residual confounding are needed to establish role of MIS in survival of patients. PMID:27258522

  10. Meta-analysis of New Genome-wide Association Studies of Colorectal Cancer Risk

    PubMed Central

    Peters, Ulrike; Hutter, Carolyn M.; Hsu, Li; Schumacher, Fredrick R.; Conti, David V.; Carlson, Christopher S.; Edlund, Christopher K.; Haile, Robert W.; Gallinger, Steven; Zanke, Brent W.; Lemire, Mathieu; Rangrej, Jagadish; Vijayaraghavan, Raakhee; Chan, Andrew T.; Hazra, Aditi; Hunter, David J.; Ma, Jing; Fuchs, Charles S.; Giovannucci, Edward L.; Kraft, Peter; Liu, Yan; Chen, Lin; Jiao, Shuo; Makar, Karen W.; Taverna, Darin; Gruber, Stephen B.; Rennert, Gad; Moreno, Victor; Ulrich, Cornelia M.; Woods, Michael O.; Green, Roger C.; Parfrey, Patrick S.; Prentice, Ross L.; Kooperberg, Charles; Jackson, Rebecca D.; LaCroix, Andrea Z.; Caan, Bette J.; Hayes, Richard B.; Berndt, Sonja I.; Chanock, Stephen J.; Schoen, Robert E.; Chang-Claude, Jenny; Hoffmeister, Michael; Brenner, Hermann; Frank, Bernd; Bézieau, Stéphane; Küry, Sébastien; Slattery, Martha L.; Hopper, John L.; Jenkins, Mark A.; Le Marchand, Loic; Lindor, Noralane M.; Newcomb, Polly A.; Seminara, Daniela; Hudson, Thomas J.; Duggan, David J.; Potter, John D.; Casey, Graham

    2011-01-01

    Colorectal cancer is the second leading cause of cancer death in developed countries. Genome-wide association studies (GWAS) have successfully identified novel susceptibility loci for colorectal cancer. To follow-up on these findings, and try to identify novel colorectal cancer susceptibility loci, we present results for genome-wide association studies (GWAS) of colorectal cancer (2,906 cases, 3,416 controls) that have not previously published main associations. Specifically, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) using log-additive models for each study. In order to improve our power to detect novel colorectal cancer susceptibility loci, we performed a meta-analysis combining the results across studies. We selected the most statistically significant single nucleotide polymorphisms (SNPs) for replication using 10 independent studies (8,161 cases and 9,101 controls). We again used a meta-analysis to summarize results for the replication studies alone, and for a combined analysis of GWAS and replication studies. We measured 10 SNPs previously identified in colorectal cancer susceptibility loci and found eight to be associated with colorectal cancer (p-value range: 0.02 to 1.8 × 10−8). When we excluded studies that have previously published on these SNPs, five SNPs remained significant at p<0.05 in the combined analysis. No novel susceptibility loci were significant in the replication study after adjustment for multiple testing, and none reached genome-wide significance from a combined analysis of GWAS and replication. We observed marginally significant evidence for a second independent SNP in the BMP2 region at chromosomal location 20p12 (rs4813802; replication p-value 0.03; combined p-value 7.3 × 10−5). In a region on 5p33.15, which includes the coding regions of the TERT-CLPTM1L genes and has been identified in GWAS to be associated with susceptibility to at least seven other cancers, we observed a marginally significant

  11. Modeling and Control of Colorectal Cancer.

    PubMed

    Song, Li-Peng; Wang, Hao-Yu

    2016-01-01

    Colorectal Cancer (CRC) is becoming a major threat to people's life in China. Screening methods adopted by many other countries as effective counter-cancer methods have not been explicitly explored for people there. Thus, we present a Markov model with detailed precancerous adenoma states and then evaluate various screening strategies in this paper. Different from current researches, our model considers the population's heterogeneous risk of developing adenomas and observation-based screening strategies. Furthermore, we also give a new cost-effectiveness metric. After calibrating, the model is simulated using the Monte Carlo method. Numerical results show that there are threshold values of compliance rates below which strategy with every ten-year colonoscopy becomes the most cost-effective method; otherwise, an observation-based screening strategy is the most cost-effective. We also find that strategy with single colonoscopy for adenoma-free individuals and every three-year colonoscopy for those with adenoma is recommended when the observation-based strategy is not considered. Our findings give an explicit and complete instruction in CRC screening protocol in average-risk Chinese. PMID:27536786

  12. Modeling and Control of Colorectal Cancer

    PubMed Central

    Song, Li-Peng; Wang, Hao-Yu

    2016-01-01

    Colorectal Cancer (CRC) is becoming a major threat to people’s life in China. Screening methods adopted by many other countries as effective counter-cancer methods have not been explicitly explored for people there. Thus, we present a Markov model with detailed precancerous adenoma states and then evaluate various screening strategies in this paper. Different from current researches, our model considers the population’s heterogeneous risk of developing adenomas and observation-based screening strategies. Furthermore, we also give a new cost-effectiveness metric. After calibrating, the model is simulated using the Monte Carlo method. Numerical results show that there are threshold values of compliance rates below which strategy with every ten-year colonoscopy becomes the most cost-effective method; otherwise, an observation-based screening strategy is the most cost-effective. We also find that strategy with single colonoscopy for adenoma-free individuals and every three-year colonoscopy for those with adenoma is recommended when the observation-based strategy is not considered. Our findings give an explicit and complete instruction in CRC screening protocol in average-risk Chinese. PMID:27536786

  13. Novel RNA variants in colorectal cancers

    PubMed Central

    Alagaratnam, Sharmini; Zhao, Sen; Nome, Torfinn; Løvf, Marthe; Bakken, Anne C.; Hektoen, Merete; Sveen, Anita; Lothe, Ragnhild A.; Skotheim, Rolf I.

    2015-01-01

    With an annual estimated incidence of 1.4 million, and a five-year survival rate of 60%, colorectal cancer (CRC) is a major clinical burden. To identify novel RNA variants in CRC, we analyzed exon-level microarray expression data from a cohort of 202 CRCs. We nominated 25 genes with increased expression of their 3′ parts in at least one cancer sample each. To efficiently investigate underlying transcript structures, we developed an approach using rapid amplification of cDNA ends followed by high throughput sequencing (RACE-seq). RACE products from the targeted genes in 23 CRC samples were pooled together and sequenced. We identified VWA2-TCF7L2, DHX35-BPIFA2 and CASZ1-MASP2 as private fusion events, and novel transcript structures for 17 of the 23 other candidate genes. The high-throughput approach facilitated identification of CRC specific RNA variants. These include a recurrent read-through fusion transcript between KLK8 and KLK7, and a splice variant of S100A2. Both of these were overrepresented in CRC tissue and cell lines from external RNA-seq datasets. PMID:26474385

  14. Colorectal Cancer Screening: Tests, Strategies, and Perspectives

    PubMed Central

    Stracci, Fabrizio; Zorzi, Manuel; Grazzini, Grazia

    2014-01-01

    Screening has a central role in colorectal cancer (CRC) control. Different screening tests are effective in reducing CRC-specific mortality. Influence on cancer incidence depends on test sensitivity for pre-malignant lesions, ranging from almost no influence for guaiac-based fecal occult blood testing (gFOBT) to an estimated reduction of 66–90% for colonoscopy. Screening tests detect lesions indirectly in the stool [gFOBT, fecal immunochemical testing (FIT), and fecal DNA] or directly by colonic inspection [flexible sigmoidoscopy, colonoscopy, CT colonography (CTC), and capsule endoscopy]. CRC screening is cost-effective compared to no screening but no screening strategy is clearly better than the others. Stool tests are the most widely used in worldwide screening interventions. FIT will soon replace gFOBT. The use of colonoscopy as a screening test is increasing and this strategy has superseded all alternatives in the US and Germany. Despite its undisputed importance, CRC screening is under-used and participation rarely reaches 70% of target population. Strategies to increase participation include ensuring recommendation by physicians, introducing organized screening and developing new, more acceptable tests. Available evidence for DNA fecal testing, CTC, and capsule endoscopy is reviewed. PMID:25386553

  15. Lack of association between human papillomavirus infection and colorectal cancer

    PubMed Central

    Taherian, Hanieh; Fard, Zahra Tahmasebi; Abdirad, Afshin

    2014-01-01

    Introduction Colorectal cancer is the third leading cause of cancer-related deaths worldwide, with nearly one million new cases identified annually. Different factors might cause colorectal cancer, one of the most prevalent cancers among both men and women. Viral aetiology in cancerous malignancies is a very important issue and so far a number of viral strains have been identified as tumour oncogene viruses. Viral infections, such as human papillomavirus (HPV), have recently been suggested as a risk factor for colorectal cancer. However, the aetiology of the disease is still unknown. Aim To assessed the association between HPV infection and colorectal cancer. Material and methods In this study, 50 cancer tissue samples and 50 samples without colon cancer were studied in order to identify HPV through polymerase chain reaction (PCR). Of 42 adenocarcinomas, 10 were well differentiated, 30 moderated differentiated, and 2 were poorly differentiated. DNA extraction was verified by beta globin gene amplification; specific PCR was carried out based on HPV L1 consensus primers MY09/MY11. Results HPV DNA was not identified in any of the normal, adenocarcinoma, or adenoma samples. Conclusions In contrast with previous studies, the current research failed to establish a relationship between HPV infection and the incidence of colon cancer. Considering the existing inconsistencies, it is recommended that further studies be conducted with larger sample size. PMID:25396002

  16. Metabolites of tobacco smoking and colorectal cancer risk.

    PubMed

    Cross, Amanda J; Boca, Simina; Freedman, Neal D; Caporaso, Neil E; Huang, Wen-Yi; Sinha, Rashmi; Sampson, Joshua N; Moore, Steven C

    2014-07-01

    Colorectal cancer is not strictly considered a tobacco-related malignancy, but modest associations have emerged from large meta-analyses. Most studies, however, use self-reported data, which are subject to misclassification. Biomarkers of tobacco exposure may reduce misclassification and provide insight into metabolic variability that potentially influences carcinogenesis. Our aim was to identify metabolites that represent smoking habits and individual variation in tobacco metabolism, and investigate their association with colorectal cancer. In a nested case-control study of 255 colorectal cancers and 254 matched controls identified in the Prostate, Lung, Colorectal and Ovarian cancer screening trial, baseline serum was used to identify metabolites by ultra-high-performance liquid-phase chromatography and mass spectrometry, as well as gas chromatography with tandem mass spectrometry. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression. Self-reported current smoking was associated with serum cotinine, O-cresol sulfate and hydroxycotinine. Self-reported current smoking of any tobacco (OR = 1.90, 95% CI: 1.02-3.54) and current cigarette smoking (OR = 1.51, 95% CI: 0.75-3.04) were associated with elevated colorectal cancer risks, although the latter was not statistically significant. Individuals with detectable levels of hydroxycotinine had an increased colorectal cancer risk compared with those with undetectable levels (OR = 2.68, 95% CI: 1.33-5.40). Although those with detectable levels of cotinine had a suggestive elevated risk of this malignancy (OR = 1.81, 95% CI: 0.98-3.33), those with detectable levels of O-cresol sulfate did not (OR = 1.16, 95% CI: 0.57-2.37). Biomarkers capturing smoking behavior and metabolic variation exhibit stronger associations with colorectal cancer than self-report, providing additional evidence for a role for tobacco in this malignancy.

  17. Metabolites of tobacco smoking and colorectal cancer risk.

    PubMed

    Cross, Amanda J; Boca, Simina; Freedman, Neal D; Caporaso, Neil E; Huang, Wen-Yi; Sinha, Rashmi; Sampson, Joshua N; Moore, Steven C

    2014-07-01

    Colorectal cancer is not strictly considered a tobacco-related malignancy, but modest associations have emerged from large meta-analyses. Most studies, however, use self-reported data, which are subject to misclassification. Biomarkers of tobacco exposure may reduce misclassification and provide insight into metabolic variability that potentially influences carcinogenesis. Our aim was to identify metabolites that represent smoking habits and individual variation in tobacco metabolism, and investigate their association with colorectal cancer. In a nested case-control study of 255 colorectal cancers and 254 matched controls identified in the Prostate, Lung, Colorectal and Ovarian cancer screening trial, baseline serum was used to identify metabolites by ultra-high-performance liquid-phase chromatography and mass spectrometry, as well as gas chromatography with tandem mass spectrometry. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression. Self-reported current smoking was associated with serum cotinine, O-cresol sulfate and hydroxycotinine. Self-reported current smoking of any tobacco (OR = 1.90, 95% CI: 1.02-3.54) and current cigarette smoking (OR = 1.51, 95% CI: 0.75-3.04) were associated with elevated colorectal cancer risks, although the latter was not statistically significant. Individuals with detectable levels of hydroxycotinine had an increased colorectal cancer risk compared with those with undetectable levels (OR = 2.68, 95% CI: 1.33-5.40). Although those with detectable levels of cotinine had a suggestive elevated risk of this malignancy (OR = 1.81, 95% CI: 0.98-3.33), those with detectable levels of O-cresol sulfate did not (OR = 1.16, 95% CI: 0.57-2.37). Biomarkers capturing smoking behavior and metabolic variation exhibit stronger associations with colorectal cancer than self-report, providing additional evidence for a role for tobacco in this malignancy. PMID:24648381

  18. Television Watching and Colorectal Cancer Survival in Men

    PubMed Central

    Cao, Yin; Meyerhardt, Jeffrey A.; Chan, Andrew T.; Wu, Kana; Fuchs, Charles S.; Giovannucci, Edward L.

    2015-01-01

    Purpose To assess the association between pre- and postdiagnostic time spent sitting watching TV as well as other sedentary behaviors (other sitting at home and at work/driving) and mortality from colorectal cancer or other causes, and overall mortality. Methods We followed stage I-III colorectal cancer patients from the Health Professionals Follow-up Study (1986–2010). Cox models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Results 926 and 714 patients were included in the analysis of pre- and postdiagnostic TV watching respectively, and 471 and 325 died during follow-up. Prolonged prediagnostic TV viewing was associated with increased risk of colorectal cancer-specific mortality independent of leisure-time physical activity. The HRs (95% CIs) for 0–6, 7–13,14–20 and ≥21 h/wk were 1.00 (referent), 0.84 (0.56–1.25), 1.15 (0.75–1.78), 2.13 (1.31–3.45) (Ptrend=0.01). The association was observed primarily among overweight and obese individuals. Prediagnostic TV watching was also associated with overall mortality within 5 years of diagnosis, largely due to the association with colorectal cancer mortality. Other prediagnostic sitting at home or at work/driving was not associated with mortality. Postdiagnostic TV viewing was associated with non-significant increased risk of colorectal cancer-specific mortality (HR for ≥21 vs 0–6 h/wk=1.45; 95% CI 0.73–2.87) adjusting for TV viewing before diagnosis. Conclusion Prolonged prediagnostic TV watching is associated with higher colorectal cancer-specific mortality independent of leisure-time physical activity among colorectal cancer patients. PMID:26293240

  19. BRAF in metastatic colorectal cancer: the future starts now.

    PubMed

    Orlandi, Armando; Calegari, Alessandra; Inno, Alessandro; Berenato, Rosa; Caporale, Marta; Niger, Monica; Bossi, Ilaria; Di Bartolomeo, Maria; de Braud, Filippo; Pietrantonio, Filippo

    2015-12-01

    BRAF mutations are detectable in about 5-15% of metastatic colorectal cancer (mCRC) patients and represent a clear negative prognostic factor. While in BRAF-mutated (BRAFmt) metastatic melanoma TKI target therapies (BRAF and MEK inhibitor), both alone or in combination, have shown significant efficacy, in BRAFmt CRC single-agent BRAF-inhibitors as well as chemotherapy seem to be ineffective. The critical role of EGFR in CRC and its multiple downstreaming pathways seem to be involved in this lack of response. In recent years, preclinical investigations and retrospective studies slowly increased our knowledge on BRAFmt CRC. This review analyses preclinical data and discusses several clinical trials in order to explore new therapeutic strategies targeting BRAFmt mCRC.

  20. Colorectal Cancer “Methylator Phenotype”: Fact or Artifact?1

    PubMed Central

    Anacleto, Charles; Leopoldino, Andréia M; Rossi, Benedito; Soares, Fernando A; Lopes, Ademar; Rocha, José Cláudio C; Caballero, Otávia; Camargo, Anamaria A; Simpson, Andrew J G; Pena, Sérgio D J

    2005-01-01

    Abstract It has been proposed that human colorectal tumors can be classified into two groups: one in which methylation is rare, and another with methylation of several loci associated with a “CpG island methylated phenotype (CIMP),” characterized by preferential proximal location in the colon, but otherwise poorly defined. There is considerable overlap between this putative methylator phenotype and the well-known mutator phenotype associated with microsatellite instability (MSI). We have examined hypermethylation of the promoter region of five genes (DAPK, MGMT, hMLH1, p16INK4a, and p14ARF) in 106 primary colorectal cancers. A graph depicting the frequency of methylated loci in the series of tumors showed a continuous, monotonically decreasing distribution quite different from the previously claimed discontinuity. We observed a significant association between the presence of three or more methylated loci and the proximal location of the tumors. However, if we remove from analysis the tumors with hMLH1 methylation or those with MSI, the significance vanishes, suggesting that the association between multiple methylations and proximal location was indirect due to the correlation with MSI. Thus, our data do not support the independent existence of the so-called methylator phenotype and suggest that it rather may represent a statistical artifact caused by confounding of associations. PMID:15967110

  1. Map syndrome (MYH Associated Polyposis) colorectal cancer, etiopathological connections

    PubMed Central

    Ion, D; Stoian, RV; Serban, MB

    2011-01-01

    The case presented raised our scientific curiosity and it is worthy of being brought in front of the medical audience because of several reasons presented below. Presently, there are 3 hereditary syndromes that have a demonstrated etiological relationship with the colorectal cancer: Familiar Adenomatous Polyposis (FAP syndrome), HNPCC syndrome (Hereditary Nonpoliposis Colorectal Cancer) and MAP syndrome. Discovered only in 2002, the MAP syndrome (MYH associated polyposis) is the first hereditary syndrome that has autosomal recessive transmission. The APC gene can be mutated in several ways during the colonic oncogenesis: congenital in the FAP syndrome, somatic in sporadic colorectal cancers and secondary to the MYH gene inactivation in MAP syndrome. MAP phenotype is similar to the FAP phenotype because of the somatic mutations to the APC gene. Colonic polyposis is lower than FAP syndrome and appeared later, in the 40's and 50's. Colorectal cancers are frequent and discovered in the same moment as the colonic polyposis. Patients are diagnosed mostly in cancer stages. Colonoscopy shows polyps disseminated around the entire colic frame. Treatment in these cases is total rectocolectomy with ileoanal anastomosis. When working in a general emergency surgery clinic, physicians are often faced with colorectal cancers in different evolutive stages, and mostly they are faced with their complications. PMID:21505584

  2. Cytoreductive Surgery plus HIPEC for Peritoneal Metastases from Colorectal Cancer.

    PubMed

    Bhatt, Aditi; Goéré, Diane

    2016-06-01

    Occurring either synchronously or metachronously to the primary tumor, peritoneal metastases (PM) are diagnosed in 8 to 20 % of the patients with colorectal cancer (CRC). Prognosis of these patients appears to be worse than those with other sites of metastases. While systemic therapy has shown significant prolongation of survival in patients with stage IV colorectal cancer, the outcomes in the subset of patients with PM has been much inferior. Over the last 2 decades, cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) have been effective in substantially prolonging survival in patients with colorectal PM and have the potential to cure certain patients as well. This article reviews the current evidence for CRS and HIPEC to treat colorectal PM as well as future research going on in this form of locoregional treatment. PMID:27065708

  3. Breast Cancer Survivorship Care: Targeting a Colorectal Cancer Education Intervention

    PubMed Central

    Homan, Sherri G.; Yun, Shumei; Stewart, Bob R.; Armer, Jane M.

    2015-01-01

    Breast cancer survivors are at risk of developing a second primary cancer. Colorectal cancer (CRC) is one of the leading second primary cancers, and it is often preventable. We developed a multi-component educational tool to inform and encourage women breast cancer survivors to engage in CRC screening. To assess the strengths and weakness of the tool and to improve the relevancy to the target audience, we convened four focus groups of women breast cancer survivors in Missouri. We also assessed the potential impact of the tool on the knowledge, attitudes, and beliefs regarding CRC and collected information on the barriers to CRC screening through pre- and post-focus groups’ questionnaires. A total of 43 women breast cancer survivors participated and provided very valuable suggestions on design and content to update the tool. Through the process and comparing pre- and post-focus group assessments, a significantly higher proportion of breast cancer survivors strongly agreed or agreed that CRC is preventable (78.6% vs. 96.9%, p = 0.02) and became aware that they were at a slightly increased risk for CRC (18.6% vs. 51.7%, p = 0.003). The most cited barrier was the complexity of preparation for colonoscopy. PMID:26258794

  4. Towards automatic patient selection for chemotherapy in colorectal cancer trials

    NASA Astrophysics Data System (ADS)

    Wright, Alexander; Magee, Derek; Quirke, Philip; Treanor, Darren E.

    2014-03-01

    A key factor in the prognosis of colorectal cancer, and its response to chemoradiotherapy, is the ratio of cancer cells to surrounding tissue (the so called tumour:stroma ratio). Currently tumour:stroma ratio is calculated manually, by examining H&E stained slides and counting the proportion of area of each. Virtual slides facilitate this analysis by allowing pathologists to annotate areas of tumour on a given digital slide image, and in-house developed stereometry tools mark random, systematic points on the slide, known as spots. These spots are examined and classified by the pathologist. Typical analyses require a pathologist to score at least 300 spots per tumour. This is a time consuming (10- 60 minutes per case) and laborious task for the pathologist and automating this process is highly desirable. Using an existing dataset of expert-classified spots from one colorectal cancer clinical trial, an automated tumour:stroma detection algorithm has been trained and validated. Each spot is extracted as an image patch, and then processed for feature extraction, identifying colour, texture, stain intensity and object characteristics. These features are used as training data for a random forest classification algorithm, and validated against unseen image patches. This process was repeated for multiple patch sizes. Over 82,000 such patches have been used, and results show an accuracy of 79%, depending on image patch size. A second study examining contextual requirements for pathologist scoring was conducted and indicates that further analysis of structures within each image patch is required in order to improve algorithm accuracy.

  5. Non-coding landscapes of colorectal cancer

    PubMed Central

    Ragusa, Marco; Barbagallo, Cristina; Statello, Luisa; Condorelli, Angelo Giuseppe; Battaglia, Rosalia; Tamburello, Lucia; Barbagallo, Davide; Di Pietro, Cinzia; Purrello, Michele

    2015-01-01

    For two decades Vogelstein’s model has been the paradigm for describing the sequence of molecular changes within protein-coding genes that would lead to overt colorectal cancer (CRC). This model is now too simplistic in the light of recent studies, which have shown that our genome is pervasively transcribed in RNAs other than mRNAs, denominated non-coding RNAs (ncRNAs). The discovery that mutations in genes encoding these RNAs [i.e., microRNAs (miRNAs), long non-coding RNAs, and circular RNAs] are causally involved in cancer phenotypes has profoundly modified our vision of tumour molecular genetics and pathobiology. By exploiting a wide range of different mechanisms, ncRNAs control fundamental cellular processes, such as proliferation, differentiation, migration, angiogenesis and apoptosis: these data have also confirmed their role as oncogenes or tumor suppressors in cancer development and progression. The existence of a sophisticated RNA-based regulatory system, which dictates the correct functioning of protein-coding networks, has relevant biological and biomedical consequences. Different miRNAs involved in neoplastic and degenerative diseases exhibit potential predictive and prognostic properties. Furthermore, the key roles of ncRNAs make them very attractive targets for innovative therapeutic approaches. Several recent reports have shown that ncRNAs can be secreted by cells into the extracellular environment (i.e., blood and other body fluids): this suggests the existence of extracellular signalling mechanisms, which may be exploited by cells in physiology and pathology. In this review, we will summarize the most relevant issues on the involvement of cellular and extracellular ncRNAs in disease. We will then specifically describe their involvement in CRC pathobiology and their translational applications to CRC diagnosis, prognosis and therapy. PMID:26556998

  6. An in vivo rat model for early development of colorectal cancer metastasis to liver.

    PubMed

    Robertson, John H P; Yang, Shi Yu; Iga, Arthur M; Seifalian, Alexander M; Winslet, Marc C

    2008-12-01

    At diagnosis of colorectal cancer, approximately 25% of the patients have established colorectal liver metastasis. Optimal management of disseminated disease requires therapies targeting multiple stages in hepatic colorectal cancer metastasis development. To facilitate this, biologically accurate in vivo models are required. Early colonic cancer liver metastases development was studied using BDIX and Sprague-Dawley rat strains with human HT29 and rat DHDK12 colonic cancer cell lines. Different cancer cell-host combinations were used. Rat DHDK12 was previously chemically induced in the BDIX rat. Real-time intra-vital microscopy was employed to analyse the early development of liver metastases in four groups (n = 6 per group) (HT29-BDIX, DHDK12-BDIX, HT29-SD and DHDK12-SD). Data were compared using one-way anova with Bonferroni's multiple comparison test. The total number of tumour cells visualized, adherent cells within the hepatic sinusoids, extravasated tumour cells and migration rates were significantly higher in the DHDK12-BDIX combination. Maximum number of visualized cells and maximum migration rate were also significantly higher in this group. No significant differences were observed in these experimental parameters among the other three groups or in the haemodynamic parameters among all groups. In conclusion, cancer cell line-host selection has a significant effect on early colonic cancer liver metastasis development.

  7. Neoadjuvant chemotherapy for patients with liver metastases from colorectal cancer.

    PubMed

    Mandalà, Mario; Mosconi, Stefania; Quadri, Antonello; Milesi, Laura; Labianca, Roberto

    2007-06-01

    Colorectal cancer is the second most common type of cancer in industrialized countries. Despite improved resection procedures and optimized adjuvant chemotherapy, local or distant recurrences occur in 22-25% of patients with stage II/III colon cancer. Approximately 30% of patients have advanced disease at presentation. The liver is the most common site of colorectal metastases and, interestingly, 20-30% of patients with colorectal cancer have liver-only metastases. The combined modality of chemotherapy and surgery increases overall survival and the chance of cure for metastatic patients, even if there is no agreement in terms of the best schedule and how long the treatment must last. In this paper, we review the role and the rationale of neoadjuvant chemotherapy within a multimodal approach, and discuss remaining questions and future directions.

  8. Tea, Coffee, and Milk Consumption and Colorectal Cancer Risk

    PubMed Central

    Green, Chadwick John; de Dauwe, Palina; Boyle, Terry; Tabatabaei, Seyed Mehdi; Fritschi, Lin; Heyworth, Jane Shirley

    2014-01-01

    Background Data regarding the effects of tea, coffee, and milk on the risk of colorectal cancer are inconsistent. We investigated associations of tea, coffee, and milk consumption with colorectal cancer risk and attempted to determine if these exposures were differentially associated with the risks of proximal colon, distal colon, and rectal cancers. Methods Data from 854 incident cases and 948 controls were analyzed in a case-control study of colorectal cancer in Western Australia during 2005–07. Multivariable logistic regression was used to analyze the associations of black tea (with and without milk), green tea, herbal tea, hot coffee, iced coffee, and milk with colorectal cancer. Results Consumption of 1 or more cups of herbal tea per week was associated with a significantly decreased risk of distal colon cancer (adjusted odds ratio, 0.37; 95% CI, 0.16–0.82; PTrend = 0.044), and consumption of 1 or more cups of iced coffee per week was associated with increased risk of rectal cancer (adjusted odds ratio, 1.52; 95% CI, 0.91–2.54; PTrend = 0.004). Neither herbal tea nor iced coffee was associated with the risk of proximal colon cancer. Hot coffee was associated with a possible increased risk of distal colon cancer. Black tea (with or without milk), green tea, decaffeinated coffee, and milk were not significantly associated with colorectal cancer risk. Conclusions Consumption of herbal tea was associated with reduced risk of distal colon cancer, and consumption of iced coffee was associated with increased rectal cancer risk. PMID:24531002

  9. 77 FR 11123 - Scientific Information Request on Local Therapies for Unresectable Colorectal Cancer Metastases...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-24

    ... Therapies for Unresectable Colorectal Cancer Metastases to the Liver AGENCY: Agency for Healthcare Research... unresectable colorectal cancer metastases to the liver. The EHC Program is dedicated to identifying as many... manufacturers of unresectable colorectal cancer medical devices. Scientific information is being solicited...

  10. 42 CFR 410.37 - Colorectal cancer screening tests: Conditions for and limitations on coverage.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 2 2013-10-01 2013-10-01 false Colorectal cancer screening tests: Conditions for...) BENEFITS Medical and Other Health Services § 410.37 Colorectal cancer screening tests: Conditions for and...) Colorectal cancer screening tests means any of the following procedures furnished to an individual for...

  11. 42 CFR 410.37 - Colorectal cancer screening tests: Conditions for and limitations on coverage.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 2 2012-10-01 2012-10-01 false Colorectal cancer screening tests: Conditions for...) BENEFITS Medical and Other Health Services § 410.37 Colorectal cancer screening tests: Conditions for and...) Colorectal cancer screening tests means any of the following procedures furnished to an individual for...

  12. 42 CFR 410.37 - Colorectal cancer screening tests: Conditions for and limitations on coverage.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Colorectal cancer screening tests: Conditions for...) BENEFITS Medical and Other Health Services § 410.37 Colorectal cancer screening tests: Conditions for and...) Colorectal cancer screening tests means any of the following procedures furnished to an individual for...

  13. 42 CFR 410.37 - Colorectal cancer screening tests: Conditions for and limitations on coverage.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 2 2014-10-01 2014-10-01 false Colorectal cancer screening tests: Conditions for...) BENEFITS Medical and Other Health Services § 410.37 Colorectal cancer screening tests: Conditions for and...) Colorectal cancer screening tests means any of the following procedures furnished to an individual for...

  14. 42 CFR 410.37 - Colorectal cancer screening tests: Conditions for and limitations on coverage.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 2 2011-10-01 2011-10-01 false Colorectal cancer screening tests: Conditions for...) BENEFITS Medical and Other Health Services § 410.37 Colorectal cancer screening tests: Conditions for and...) Colorectal cancer screening tests means any of the following procedures furnished to an individual for...

  15. Body fat and risk of colorectal cancer among postmenopausal women.

    PubMed

    Kabat, Geoffrey C; Heo, Moonseong; Wactawski-Wende, Jean; Messina, Catherine; Thomson, Cynthia A; Wassertheil-Smoller, Sylvia; Rohan, Thomas E

    2013-06-01

    Studies of the relationship between anthropometric indices of obesity and colorectal cancer risk in women have shown only weak and inconsistent associations. Given the limitations of such indices, we used dual-energy X-ray absorptiometry (DXA)-derived measures of body fat obtained in the Women's Health Initiative to examine the association between body fat and risk of incident colorectal cancer. We compared these risk estimates with those obtained using conventional anthropometric measurements (body mass index and waist circumference). After exclusions, the study population consisted of 11,124 postmenopausal women with DXA measurements at baseline and no history of colorectal cancer. After a median follow-up period of 12.9 years, 169 incident colorectal cancer cases were ascertained. Cox's proportional hazards models were used to estimate hazard ratios and 95 % confidence intervals for the exposures of interest. Neither DXA-derived body fat measures nor anthropometric measures showed significant associations with risk. In view of the limited number of cases, we cannot rule out the existence of weak associations of these measures with risk of colorectal cancer. PMID:23546610

  16. Iranian Dietary Patterns and Risk of Colorectal Cancer

    PubMed Central

    Azizi, Hosein; Asadollahi, Khairollah; Davtalab Esmaeili, Elham; Mirzapoor, Mohammad

    2015-01-01

    Background: Role of diet on colorectal cancer (CRC) has been considered in terms of single foods and nutrients, but less frequently in terms of dietary patterns in Iran. The objective of this study was to determine the association between Iranian dietary patterns and CRC. Methods: This case–control study was conducted in four hospitals in Tabriz City of Iran including 414 participants aged 35–75 years:207 cases with CRC confirmed by pathology and colonoscopy findings were selected and 207 controls free of neoplastic conditions and diet-related chronic diseases (from the same hospital at the same period for the cases). Dietary data were assessed using a 123-item semi-quantitative food frequency questionnaire. Two dietary patterns were found by using of Principal Component Analysis (PCA) method;“Healthy pattern”and “Iranian pattern”. Multivariate logistic regression analysis was used to estimate adjusted odds ratios (OR) for relationship between dietary patterns and colorectal cancer. Results: After adjusting for confounding factors, the Iranian dietary pattern was significantly associated with an increased odds of colorectal cancer (OR= 1.46; 95% Confidenec Interval (CI)=1.05–2.19) while a reduced odds of colorectal cancer was observed with the Healthy dietary pattern (OR=0.18; 95% CI= 0.091-0.47). Conclusion: Iranian dietary pattern (IDP) seems to increase the odds of colorectal cancer and protective effect of Healthy dietary pattern. PMID:26000248

  17. Screening for colorectal cancer: using data to set prevention priorities

    PubMed Central

    McGowan, Lucy D’Agostino; James, Aimee S.; Bohlke, Kari; Goodman, Melody S.

    2013-01-01

    Introduction Adherence to colorectal cancer screening recommendations is known to vary by state, but less information is available about within-state variability. In the current study, we assess county-level screening rates for Missouri, with the goal of better targeting public health efforts to increase screening. Methods Prevalence of colorectal cancer screening among Missouri adults between the ages of 50 and 74 was obtained from 2008 and 2010 Behavioral Risk Factor Surveillance System data. We used multilevel logistic regression to generate county-specific estimates. After excluding 77 counties with fewer than 30 respondents, information was available about 3,739 individuals in 37 counties, representing 78.5 % of the state population. Results Across counties, the prevalence of being up-to-date with recommended colorectal cancer screening ranged from 25 to 70 %. Conclusion State-level information about colorectal cancer screening masks substantial within-state variability. Assessing and monitoring county-level disparities in screening can guide public health efforts to increase screening and reduce colorectal cancer mortality. More complete population survey data will make such analysis possible. PMID:24146228

  18. Evaluating the treatment of metastatic colorectal cancer with monoclonal antibodies

    PubMed Central

    Popa, C; Ionescu, S; Mihăilă, D; Gal, I; Potecă, T; Simion, S

    2012-01-01

    The ability to tailor biologic therapy based on the status of tumor biomarkers and monoclonal antibodies has become very important in the last years. The role of tumor biomarkers in treating colorectal cancer, specifically the K-RAS gene, was identified. K-RAS had a higher interest after Lievre and colleagues reported at the 2008 American Society of Clinical Oncology (ASCO) meeting, their analysis of K-RAS mutations in tumors from patients who did not appear to benefit from cetuximab therapy, providing additional data involving K-RAS mutant tumors and their lack of response to cetuximab, as part of first-line therapy for metastatic colorectal cancer. Furthermore, other trials evaluated the K-RAS status and the first-line treatment of metastatic colorectal cancer, the treatment of refractory metastatic cancer and dual-antibody therapy in the first-line treatment of colorectal cancer. Patients with mutant K-RAS colorectal tumors have no benefit from cetuximab, no matter the type of chemotherapy regimen. PMID:22802884

  19. Lifestyle modification: A primary prevention approach to colorectal cancer

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Early detection of cancer through screening is an important step in decreasing both morbidity and mortality. Likewise, specific modifiable lifestyle behaviors are associated with reduced risk of colorectal cancer. Lifestyle practices have also been shown to maximize health after the primary treatmen...

  20. Risk and surveillance of individuals with heritable factors for colorectal cancer. WHO Collaborating Centre for the Prevention of Colorectal Cancer.

    PubMed Central

    Burt, R. W.; Bishop, D. T.; Lynch, H. T.; Rozen, P.; Winawer, S. J.

    1990-01-01

    Heritable and genetic factors pertinent to colon cancer can be divided into three categories: inherited syndromes, genetic epidemiology, and molecular genetics. Familial adenomatous polyposis (FAP) and Gardner syndrome (GS) are rare dominantly inherited syndromes characterized by hundreds to thousands of colonic adenomatous polyps. Colon cancer occurs at a young age in both diseases unless the colon is removed. Peutz-Jeghers syndrome and familial juvenile polyposis are inherited hamartomatous polyposis conditions with a less dramatic, but definite, increased risk for colon cancer. These four polyposis syndromes together account for less than 1% of cases of colon malignancy. Hereditary nonpolyposis colorectal cancer is a dominantly inherited form of colon cancer characterized by an early age of onset and a predilection for proximal colonic tumours. Multiple primary malignancies are frequently observed and one or several adenomatous polyps are often present in affected individuals; 4-6% of colon cancer cases occur in relationship to this syndrome. Genetic epidemiological studies have consistently shown that first-degree relatives of persons with colon cancer have a twofold to threefold increased risk of having colon malignancy. More recent studies have found a similar risk among relatives of those with adenomatous polyps. Studies of colon cancer and adenomatous polyps in pedigrees have further demonstrated that this familial clustering probably occurs on the basis of partially penetrant inherited susceptibilities. These inherited susceptibilities probably interact with environmental factors to give rise to polyp growth and finally colon cancer. Molecular studies have begun to elucidate the genetic mechanisms of colon cancer at the DNA level. The germinal mutation of FAP and GS has been localized to the long arm of chromosome 5. Tissue samples from "random" adenomatous polyps and colon cancers have shown frequent and specific acquired DNA sequence deletions on

  1. Aetiology of colorectal cancer and relevance of monogenic inheritance

    PubMed Central

    Ponz de Leon, M; Benatti, P; Borghi, F; Pedroni, M; Scarselli, A; Di Gregorio, C; Losi, L; Viel, A; Genuardi, M; Abbati, G; Rossi, G; Menigatti, M; Lamberti, I; Ponti, G; Roncucci, L

    2004-01-01

    Background and aims: Although diet and lifestyle are associated with the development of colorectal malignancies, the only clearly identified aetiological factors in colorectal cancer are inheritance (hereditary non-polyposis colorectal cancer (HNPCC) and familial polyposis), inflammatory bowel diseases, papillomavirus, and acquired immunodeficiency syndrome (AIDS). Our aim was to determine what proportion of colorectal neoplasms could be attributed to these specific factors. Patients and methods: Data from a colorectal cancer registry were analysed over a 15 year period, during which nearly 2500 cases were recorded. In patients with suspected HNPCC, microsatellite instability and immunohistochemical expression of proteins encoded by the main DNA mismatch repair genes were assessed. In families with unstable neoplasms, constitutional mutations of the mismatch repair genes hMSH2, hMLH1, and hMSH6 were evaluated by single strand conformation polymorphism analysis and sequencing. Results: Inflammatory bowel diseases, familial polyposis, and AIDS were rare causes of colorectal cancer (three, three, and one case, respectively). Anal squamous carcinoma developed in 27 patients (1.0%) and could be attributed to papillomavirus infection. In 58 patients (from 34 families) a clinical diagnosis of HNPCC was established (2.4%). In total, cases with a known aetiology were 92 (3.7% of all patients). Microsatellite instability was detected in 15 cancers from HNPCC families, and germline mutations in six families (12 patients, 0.5% of the total). Families with unstable tumours, with or without mutations, were clinically similar, suggesting the involvement of the mismatch repair system even when mutations were not detected. Conclusions: The study suggests that the aetiology of colorectal malignancies remains elusive in the large majority of cases. Among specific causes, HNPCC represents the most frequent. However, with a population based approach, constitutional mutations of the

  2. Colorectal cancer detection in a rural community

    PubMed Central

    Cotterill, Mike; Gasparelli, Rudy; Kirby, Erle

    2005-01-01

    PROBLEM BEING ADDRESSED Colorectal cancer (CRC) is a substantial cause of death and morbidity in Canada. Endoscopy screening by colonoscopy has been recommended, but widespread implementation is impossible because it is difficult to obtain, especially in rural areas. OBJECTIVE OF PROGRAM To screen for CRC safely and effectively using colonoscopy performed by non-specialist endoscopists in rural areas. PROGRAM DESCRIPTION Health providers and community organizations were informed about the screening program. Patients between the ages of 50 and 75 and those at high risk of CRC based on family history were screened. Measures of safety and effectiveness were monitored. In 2 years of screening, one of 152 patients was found to have CRC, and 23.7% had adenomatous polyps. There were no complications. Rates of CRC and adenoma detection and cecal intubation were similar to rates found in other screening studies. CONCLUSION It was not difficult to design and implement a CRC screening program in our small rural community. Colonoscopies performed by family physicians have been effective, and there have been no serious complications. PMID:16190175

  3. Colorectal cancer progression: lessons from Drosophila?

    PubMed

    Bell, Graham P; Thompson, Barry J

    2014-04-01

    Human colorectal cancers arise as benign adenomas, tumours that retain their epithelial character, and then progress to malignant adenocarcinomas and carcinomas in which the epithelium becomes disrupted. Carcinomas often exhibit transcriptional downregulation of E-cadherin and other epithelial genes in an epithelial-to-mesenchymal transition (EMT), a mechanism first discovered in Drosophila to be mediated by the transcription factors Twist and Snail. In contrast, adenocarcinomas retain expression of E-cadherin and disruption of the epithelium occurs through formation of progressively smaller epithelial cysts with apical Crumbs/CRB3, Stardust/PALS1, and Bazooka/PAR3 localised to the inner lumen. Results from Drosophila show that morphologically similar cysts form upon induction of clonal heterogeneity in Wnt, Smad, or Ras signalling levels, which causes extrusion of epithelial cells at clonal boundaries. Thus, intratumour heterogeneity might also promote formation of adenocarcinomas in humans. Finally, epithelial cysts can collectively migrate, as in the case of Drosophila border cells, a potential model system for the invasive migration of adenocarcinoma cells.

  4. Colorectal cancer screening among Chinese American immigrants.

    PubMed

    Kim, Karen; Chapman, Christopher; Vallina, Helen

    2012-10-01

    The purpose of this study was to examine the factors determining fecal occult blood test (FOBT) uptake in Chinese American immigrants. This study used a prospective, cross-sectional design with convenience sampling. An educational session on colorectal cancer screening (CRS) was provided to the participants during a health fair, and each participant was offered a no-cost FOBT kit. Data was collected over two consecutive years during three different health fairs. A questionnaire was used to collect demographic data. A total of 113 participants were recruited and 72% of them returned the FOBT kit. There was a significant association between having a primary-care physician (PCP) and having CRS in the past, even after controlling for age, gender and the length of time in the US (P = .009). Participants who visited a doctor for health maintenance were less likely to participate in the FOBT, compared to participants who never visited a doctor or who only visited a doctor when they were sick (P = .001). The length of time in the US had a significant effect on having a PCP (P = .002). However, having a PCP or having CRS in the past was not associated with participating in the screening and so was feeling at risk for CRC. In fact, 49% of Chinese women and 45% of Chinese men felt no risk of CRC. Future research and interventions that address knowledge deficits and focus on recent immigrants and their access to health care may have the potential to increase CRS among Chinese American immigrants.

  5. Colorectal Cancer in African Americans: An Update

    PubMed Central

    Williams, Renee; White, Pascale; Nieto, Jose; Vieira, Dorice; Francois, Fritz; Hamilton, Frank

    2016-01-01

    This review is an update to the American College of Gastroenterology (ACG) Committee on Minority Affairs and Cultural Diversity's paper on colorectal cancer (CRC) in African Americans published in 2005. Over the past 10 years, the incidence and mortality rates of CRC in the United States has steadily declined. However, reductions have been strikingly much slower among African Americans who continue to have the highest rate of mortality and lowest survival when compared with all other racial groups. The reasons for the health disparities are multifactorial and encompass physician and patient barriers. Patient factors that contribute to disparities include poor knowledge of benefits of CRC screening, limited access to health care, insurance status along with fear and anxiety. Physician factors include lack of knowledge of screening guidelines along with disparate recommendations for screening. Earlier screening has been recommended as an effective strategy to decrease observed disparities; currently the ACG and American Society of Gastrointestinal Endoscopists recommend CRC screening in African Americans to begin at age 45. Despite the decline in CRC deaths in all racial and ethnic groups, there still exists a significant burden of CRC in African Americans, thus other strategies including educational outreach for health care providers and patients and the utilization of patient navigation systems emphasizing the importance of screening are necessary. These strategies have been piloted in both local communities and Statewide resulting in notable significant decreases in observed disparities. PMID:27467183

  6. Colorectal Cancer in African Americans: An Update.

    PubMed

    Williams, Renee; White, Pascale; Nieto, Jose; Vieira, Dorice; Francois, Fritz; Hamilton, Frank

    2016-01-01

    This review is an update to the American College of Gastroenterology (ACG) Committee on Minority Affairs and Cultural Diversity's paper on colorectal cancer (CRC) in African Americans published in 2005. Over the past 10 years, the incidence and mortality rates of CRC in the United States has steadily declined. However, reductions have been strikingly much slower among African Americans who continue to have the highest rate of mortality and lowest survival when compared with all other racial groups. The reasons for the health disparities are multifactorial and encompass physician and patient barriers. Patient factors that contribute to disparities include poor knowledge of benefits of CRC screening, limited access to health care, insurance status along with fear and anxiety. Physician factors include lack of knowledge of screening guidelines along with disparate recommendations for screening. Earlier screening has been recommended as an effective strategy to decrease observed disparities; currently the ACG and American Society of Gastrointestinal Endoscopists recommend CRC screening in African Americans to begin at age 45. Despite the decline in CRC deaths in all racial and ethnic groups, there still exists a significant burden of CRC in African Americans, thus other strategies including educational outreach for health care providers and patients and the utilization of patient navigation systems emphasizing the importance of screening are necessary. These strategies have been piloted in both local communities and Statewide resulting in notable significant decreases in observed disparities. PMID:27467183

  7. Screening for colorectal cancer: spoiled for choice?

    PubMed

    Sarfati, Diana; Shaw, Caroline; McLeod, Melissa; Blakely, Tony; Bissett, Ian

    2016-01-01

    There are many different potential screening strategies for colorectal cancer (CRC) that vary both in the likely magnitude of their benefits on CRC mortality and their impact on health services. Many approaches to CRC screening are cost-effective, but there is substantial uncertainty about the optimal approach. Decision models using Markov or microsimulation modelling that compare the cost-effectiveness of different screening strategies are useful in this regard. We have reviewed recent decision models that compare the cost-effectiveness of one-off flexible sigmoidoscopy screening with immunochemical faecal occult blood (FIT) based screening. Models consistently show that any population-based screening is cost-effective compared with no screening, and that FIT-based screening is more effective than one-off sigmoidoscopy screening. The combination of one-off sigmoidoscopy with FIT is more effective in saving lives than either modality alone, but has the greatest impact on health service resources. The recent decision to proceed with biennial FIT-based screening is consistent with current evidence. PMID:27538046

  8. Epithelial to mesenchymal transition and the cancer stem cell phenotype: Insights from cancer biology with therapeutic implications for colorectal cancer

    PubMed Central

    Findlay, Victoria J.; Wang, Cindy; Watson, Dennis K.; Camp, E. Ramsay

    2014-01-01

    Although mortality from colorectal cancer (CRC) is decreasing, colorectal cancer is still the second highest cause of cancer related deaths in America. Chemotherapy and radiation therapy now play central roles in our strategies to fight cancer, although we continue to lack novel strategies overcoming therapeutic resistance. Molecular mechanisms of therapeutic resistance in CRC continue to be under intense investigation. In this review, we highlight the recent evidence linking epithelial-to-mesenchymal transition (EMT) with aggressive tumor biology as well as with the cancer stem cells (CSC) across multiple organ systems including colon cancer. Furthermore, in the era of neo-adjuvant treatment, the clinical implications are concerning that our treatments may have the potential to induce more aggressive cancer cells through EMT, perhaps even generating CSCs more capable of metastasis and further resistant to treatment. This concern and potential reality highlights the critical need for further understanding the impact of clinical therapy on the pathobiology of cancer and further supports the need to therapeutically target the CSC. Besides serving as potential biomarkers for aggressive tumor biology and therapeutic resistance, EMT and CSC molecular pathways may highlight novel therapeutic targets as strategies for improving the response to conventional anti-neoplastic agents translating into improved oncologic outcomes. PMID:24787239

  9. Characterizing metabolic changes in human colorectal cancer.

    PubMed

    Williams, Michael D; Zhang, Xing; Park, Jeong-Jin; Siems, William F; Gang, David R; Resar, Linda M S; Reeves, Raymond; Hill, Herbert H

    2015-06-01

    Colorectal cancer (CRC) remains a leading cause of cancer death worldwide, despite the fact that it is a curable disease when diagnosed early. The development of new screening methods to aid in early diagnosis or identify precursor lesions at risk for progressing to CRC will be vital to improving the survival rate of individuals predisposed to CRC. Metabolomics is an advancing area that has recently seen numerous applications to the field of cancer research. Altered metabolism has been studied for many years as a means to understand and characterize cancer. However, further work is required to establish standard procedures and improve our ability to identify distinct metabolomic profiles that can be used to diagnose CRC or predict disease progression. The present study demonstrates the use of direct infusion traveling wave ion mobility mass spectrometry to distinguish metabolic profiles from CRC samples and matched non-neoplastic epithelium as well as metastatic and primary tumors at different stages of disease (T1-T4). By directly infusing our samples, the analysis time was reduced significantly, thus increasing the speed and efficiency of this method compared to traditional metabolomics platforms. Partial least squares discriminant analysis was used to visualize differences between the metabolic profiles of sample types and to identify the specific m/z features that led to this differentiation. Identification of the distinct m/z features was made using the human metabolome database. We discovered alterations in fatty acid biosynthesis and oxidative, glycolytic, and polyamine pathways that distinguish tumors from non-malignant colonic epithelium as well as various stages of CRC. Although further studies are needed, our results indicate that colonic epithelial cells undergo metabolic reprogramming during their evolution to CRC, and the distinct metabolites could serve as diagnostic tools or potential targets in therapy or primary prevention. Graphical Abstract

  10. Characterizing metabolic changes in human colorectal cancer.

    PubMed

    Williams, Michael D; Zhang, Xing; Park, Jeong-Jin; Siems, William F; Gang, David R; Resar, Linda M S; Reeves, Raymond; Hill, Herbert H

    2015-06-01

    Colorectal cancer (CRC) remains a leading cause of cancer death worldwide, despite the fact that it is a curable disease when diagnosed early. The development of new screening methods to aid in early diagnosis or identify precursor lesions at risk for progressing to CRC will be vital to improving the survival rate of individuals predisposed to CRC. Metabolomics is an advancing area that has recently seen numerous applications to the field of cancer research. Altered metabolism has been studied for many years as a means to understand and characterize cancer. However, further work is required to establish standard procedures and improve our ability to identify distinct metabolomic profiles that can be used to diagnose CRC or predict disease progression. The present study demonstrates the use of direct infusion traveling wave ion mobility mass spectrometry to distinguish metabolic profiles from CRC samples and matched non-neoplastic epithelium as well as metastatic and primary tumors at different stages of disease (T1-T4). By directly infusing our samples, the analysis time was reduced significantly, thus increasing the speed and efficiency of this method compared to traditional metabolomics platforms. Partial least squares discriminant analysis was used to visualize differences between the metabolic profiles of sample types and to identify the specific m/z features that led to this differentiation. Identification of the distinct m/z features was made using the human metabolome database. We discovered alterations in fatty acid biosynthesis and oxidative, glycolytic, and polyamine pathways that distinguish tumors from non-malignant colonic epithelium as well as various stages of CRC. Although further studies are needed, our results indicate that colonic epithelial cells undergo metabolic reprogramming during their evolution to CRC, and the distinct metabolites could serve as diagnostic tools or potential targets in therapy or primary prevention. Graphical Abstract

  11. Assessment of colorectal cancer incidence among polypropylene pilot plant employees

    SciTech Connect

    Acquavella, J.F.; Owen, C.V. )

    1990-02-01

    Our recent study reported a colorectal cancer excess among workers involved in the manufacture of polypropylene. To follow up on this finding, we initiated a study of colorectal cancer incidence among polypropylene pilot plant workers within the same company. The purpose of this investigation was to determine whether colorectal cancer incidence was elevated among workers who may have had exposures similar to those experienced on the commercial production unit. The study population included 183 employees who worked at least 6 months on either of two pilot plants. Overall, there were three observed colorectal cases v. 3.3 expected (standardized incidence ratio = 0.9, 90% confidence interval 0.3 to 2.3). Analyses for the process, mechanic, and laboratory subgroup showed rates consistent with expected values (3 observed, 2.8 expected; standardized incidence ratio = 1.1, 90% confidence interval 0.3 to 2.8). Analyses by duration of employment and latency did not show patterns consistent with the colorectal cancer excess previously reported. The likelihood of lower or different exposures on the pilot plant than would be found on commercial production units is discussed along with the need for studies of workers in other polypropylene manufacturing environments.

  12. Expression and clinical significance of Sirt1 in colorectal cancer

    PubMed Central

    YU, DENG-FENG; JIANG, SU-JUAN; PAN, ZHI-PENG; CHENG, WEI-DONG; ZHANG, WEN-JUN; YAO, XIAO-KUN; LI, YU-CHENG; LUN, YONG-ZHI

    2016-01-01

    The objective of the present study was to examine the expression of Silent information regulator 1 (Sirt1) in colorectal cancer and peritumoral normal mucosa tissue, and therefore analyze the role and molecular mechanism of Sirt1 in the pathogenesis of colorectal cancer. Colorectal cancer tissue specimens were employed as the experimental group, and adjacent normal mucosa tissues >5 cm from tumor lesions were used as the control group. The expression of Sirt1 was detected by the immunohistochemical streptavidin peroxidase detection method in paraffin-embedded sections, whilst Sirt1 protein expression was examined by western blot analysis in the fresh tissues. Sirt1 protein was primarily expressed in the nuclei of the tumor cells, and positive staining was brownish-yellow in color. The relative expression quantities of Sirt1 in the peritumoral normal rectal mucosa and rectal carcinoma were 1.15 and 2.62, and the differences between the two groups were statistically significant (P<0.05). The expression level of Sirt1 in colorectal carcinoma was significantly associated with the depth of tumor invasion, differentiation and tumor size (P<0.05). Sirt1 expression was also found to be associated with tumor tissue type, lymph node metastasis, Duke's stage and patient age. These characteristics combined may therefore be used as markers for the early diagnosis of colorectal cancer pathogenesis. PMID:26893713

  13. THBS2 is a Potential Prognostic Biomarker in Colorectal Cancer

    PubMed Central

    Wang, Xue; Zhang, Lei; Li, Hui; Sun, WenJie; Zhang, Honghe; Lai, Maode

    2016-01-01

    Colorectal cancer is one of the most common leading causes of death worldwide. Prognostic at an early stage is a useful way that decrease and avoid mortality. Although remarkable progress has been made to investigate the underlying mechanism, the understanding of the complicated carcinogenesis process was enormously hindered by large-scale tumor heterogeneity. Here we proposed that the prognosis-related gene THBS2, responsible for cooperativity disorientation, probably contain untapped prognostic resource of colorectal cancer. We originally established Spearman correlation transition, Kaplan–Meier survival analysis and meta-analysis that combine public dataset and clinical samples to quantify the prognostic value of THBS2. THBS2 could be considered as a novel prognostic marker in colorectal cancer. PMID:27632935

  14. THBS2 is a Potential Prognostic Biomarker in Colorectal Cancer.

    PubMed

    Wang, Xue; Zhang, Lei; Li, Hui; Sun, WenJie; Zhang, Honghe; Lai, Maode

    2016-01-01

    Colorectal cancer is one of the most common leading causes of death worldwide. Prognostic at an early stage is a useful way that decrease and avoid mortality. Although remarkable progress has been made to investigate the underlying mechanism, the understanding of the complicated carcinogenesis process was enormously hindered by large-scale tumor heterogeneity. Here we proposed that the prognosis-related gene THBS2, responsible for cooperativity disorientation, probably contain untapped prognostic resource of colorectal cancer. We originally established Spearman correlation transition, Kaplan-Meier survival analysis and meta-analysis that combine public dataset and clinical samples to quantify the prognostic value of THBS2. THBS2 could be considered as a novel prognostic marker in colorectal cancer. PMID:27632935

  15. Celebrity appeal: reaching women to promote colorectal cancer screening.

    PubMed

    Cooper, Crystale Purvis; Gelb, Cynthia A; Lobb, Kathleen

    2015-03-01

    The Centers for Disease Control and Prevention's Screen for Life: National Colorectal Cancer Action Campaign works with the Entertainment Industry Foundation's National Colorectal Cancer Research Alliance to develop public service announcements (PSAs) featuring celebrities. Selection of Screen for Life celebrity spokespersons is based on a variety of factors, including their general appeal and personal connection to colorectal cancer. Screen for Life PSAs featuring celebrities have been disseminated exclusively through donated media placements and have been formatted for television, radio, print, and out-of-home displays such as dioramas in airports, other transit stations, and shopping malls. A 2012 national survey with women aged 50-75 years (n=772) investigated reported exposure to Screen for Life PSAs featuring actor Terrence Howard. In total, 8.3% of women recalled exposure to the PSAs. Celebrity spokespersons can attract the attention of both target audiences and media gatekeepers who decide which PSAs will receive donated placements.

  16. Targeting Angiogenesis in Colorectal Cancer: Tyrosine Kinase Inhibitors.

    PubMed

    Kircher, Sheetal Mehta; Nimeiri, Halla S; Benson, Al B

    2016-01-01

    Colorectal cancer is commonly diagnosed throughout the world, and treatment options have greatly expanded over the last 2 decades. Targeting angiogenesis has been a major focus of study in a variety of malignancy types. Targeting angiogenesis has been achieved by several mechanisms in colorectal cancer, including use of antiangiogenic small molecule tyrosine kinase inhibitors (TKIs). There have been many attempts and failures to prove efficacy of TKIs in the treatment of colorectal cancer including sorafenib, sunitinib, vatalanib, and tivozanib. Regorafenib was the first TKI to demonstrate efficacy and is an orally active inhibitor of angiogenic (including the vascular endothelial growth factor receptors 1, 2, and 3), stromal, and oncogenic receptor tyrosine kinases. There are ongoing investigations of both regorafenib and ninetanib; however, there remains a critical need to better understand novel combinations with TKIs that could prove more efficacious than available options. PMID:27341596

  17. Celebrity Appeal: Reaching Women to Promote Colorectal Cancer Screening

    PubMed Central

    Cooper, Crystale Purvis; Gelb, Cynthia A.; Lobb, Kathleen

    2015-01-01

    The Centers for Disease Control and Prevention’s Screen for Life: National Colorectal Cancer Action Campaign works with the Entertainment Industry Foundation’s National Colorectal Cancer Research Alliance to develop public service announcements (PSAs) featuring celebrities. Selection of Screen for Life celebrity spokespersons is based on a variety of factors, including their general appeal and personal connection to colorectal cancer. Screen for Life PSAs featuring celebrities have been disseminated exclusively through donated media placements and have been formatted for television, radio, print, and out-of-home displays such as dioramas in airports, other transit stations, and shopping malls. A 2012 national survey with women aged 50–75 years (n = 772) investigated reported exposure to Screen for Life PSAs featuring actor Terrence Howard. In total, 8.3% of women recalled exposure to the PSAs. Celebrity spokespersons can attract the attention of both target audiences and media gatekeepers who decide which PSAs will receive donated placements. PMID:25521047

  18. Clinic-genomic association mining for colorectal cancer using publicly available datasets.

    PubMed

    Liu, Fang; Feng, Yaning; Li, Zhenye; Pan, Chao; Su, Yuncong; Yang, Rui; Song, Liying; Duan, Huilong; Deng, Ning

    2014-01-01

    In recent years, a growing number of researchers began to focus on how to establish associations between clinical and genomic data. However, up to now, there is lack of research mining clinic-genomic associations by comprehensively analysing available gene expression data for a single disease. Colorectal cancer is one of the malignant tumours. A number of genetic syndromes have been proven to be associated with colorectal cancer. This paper presents our research on mining clinic-genomic associations for colorectal cancer under biomedical big data environment. The proposed method is engineered with multiple technologies, including extracting clinical concepts using the unified medical language system (UMLS), extracting genes through the literature mining, and mining clinic-genomic associations through statistical analysis. We applied this method to datasets extracted from both gene expression omnibus (GEO) and genetic association database (GAD). A total of 23,517 clinic-genomic associations between 139 clinical concepts and 7914 genes were obtained, of which 3474 associations between 31 clinical concepts and 1689 genes were identified as highly reliable ones. Evaluation and interpretation were performed using UMLS, KEGG, and Gephi, and potential new discoveries were explored. The proposed method is effective in mining valuable knowledge from available biomedical big data and achieves a good performance in bridging clinical data with genomic data for colorectal cancer.

  19. Loss of CSMD1 or 2 may contribute to the poor prognosis of colorectal cancer patients.

    PubMed

    Zhang, Rui; Song, Chun

    2014-05-01

    CUB and sushi multiple domain protein 1 (CSMD1) is a candidate tumor suppressor gene. The three members of CSMD family have very similar structures, each consisting of 14 CUB domains separated from one another by a sushi domain, an additional uninterrupted array of sushi domains, a single transmembrane domain, and a short cytoplasmic tail. In this work, we aimed to study the protein and mRNA levels of the CSMD1, CSMD2, and CSMD3 and evaluate their prognostic importance in colorectal cancer. Reduced expressions of these three proteins were detected in colorectal cancer tissues by comparing matched normal tissues. Low CSMD2 expression was significantly associated with differentiation, lymphatic invasion, and tumor size. CSMD3 was associated with differentiation and lymphatic invasion. CSMD1 and CSMD2 expressions were associated with overall survival. This study offers convincing evidence for the first time that the three genes of CSMD family were downregulated in the patients with colorectal cancer and may be used as predictors of colorectal cancer.

  20. Loss of CSMD1 or 2 may contribute to the poor prognosis of colorectal cancer patients.

    PubMed

    Zhang, Rui; Song, Chun

    2014-05-01

    CUB and sushi multiple domain protein 1 (CSMD1) is a candidate tumor suppressor gene. The three members of CSMD family have very similar structures, each consisting of 14 CUB domains separated from one another by a sushi domain, an additional uninterrupted array of sushi domains, a single transmembrane domain, and a short cytoplasmic tail. In this work, we aimed to study the protein and mRNA levels of the CSMD1, CSMD2, and CSMD3 and evaluate their prognostic importance in colorectal cancer. Reduced expressions of these three proteins were detected in colorectal cancer tissues by comparing matched normal tissues. Low CSMD2 expression was significantly associated with differentiation, lymphatic invasion, and tumor size. CSMD3 was associated with differentiation and lymphatic invasion. CSMD1 and CSMD2 expressions were associated with overall survival. This study offers convincing evidence for the first time that the three genes of CSMD family were downregulated in the patients with colorectal cancer and may be used as predictors of colorectal cancer. PMID:24408017

  1. Programmatic screening for colorectal cancer: the COLONPREV study.

    PubMed

    Castells, Antoni; Quintero, Enrique

    2015-03-01

    The COLONPREV study is an ongoing multicenter, nationwide, randomized controlled trial aimed at evaluating the efficacy of once-only colonoscopy and biennial fecal immunochemical testing with respect to the reduction of CRC-related mortality at 10 years in average-risk colorectal cancer screening population. Following a pragmatic approach, this study may contribute to establishing the most cost-effective strategy in a programmatic, population-based setting. In this review, we report the results obtained at the first screening round, as well as others achieved in nested evaluations using the COLONPREV dataset with the aim of clarifying some controversial issues on the different strategies of colorectal cancer screening.

  2. BRAF-Directed Therapy in Metastatic Colorectal Cancer.

    PubMed

    Korphaisarn, Krittiya; Kopetz, Scott

    2016-01-01

    Activating BRAF (V-raf murine sarcoma viral oncogene homolog B) mutations occur in approximately 5% to 10% of patients with metastatic colorectal cancer, mostly V600E mutation, and it is associated with distinct clinical and pathological features. To date, there are no approved treatments to target this mutation. BRAF inhibitor monotherapy has limited efficacy, in contrast to metastatic melanoma. Combination strategies that block not only BRAF mutated kinase but other alternative pathways are ongoing and have demonstrated improved activity. This review aims to provide data about new strategies to target to BRAF gene mutation in metastatic colorectal cancer. PMID:27341594

  3. Colorectal cancer implant in an external hemorrhoidal skin tag

    PubMed Central

    Liasis, Lampros

    2016-01-01

    External hemorrhoidal skin tags are generally benign. Colorectal cancer metastases to the squamous epithelium of perianal skin tags without other evidence of disseminated disease is a very rare finding. We present the case of a 61-year-old man with metastasis to an external hemorrhoidal skin tag from a midrectal primary adenocarcinoma. This case report highlights the importance of close examination of the anus during surgical planning for colorectal cancers. Abnormal findings of the perianal skin suggesting an implant or metastatic disease warrant biopsy, as distal spread and seeding can occur. In our patient, this finding appropriately changed surgical management. PMID:27034567

  4. [Diagnostic imaging techniques for hepatic metastases from colorectal cancer].

    PubMed

    Mollerup, Talie Khadem; Lorentzen, Torben; Møller, Jakob M; Nørgaard, Henrik; Achiam, Michael P

    2015-07-27

    Hepatic metastases (HM) are amongst the most important prognostic factors in patient survival from colorectal cancer. The diagnostic imaging techniques for accurate detection and characterization of colorectal metastases are therefore vital. In a review of the literature, MRI showed the highest sensitivity for detection of HM lesions < 1 cm, but the amount of MR scanners is insufficient. Contrast-enhanced ultrasound and computed tomography have similar sensitivity for detection of HM, but each method also have limitation such as operator dependency or enhanced risk of cancer due to ionizing radiation. PMID:26238008

  5. Mutator gene and hereditary non-polyposis colorectal cancer

    DOEpatents

    de la Chapelle, Albert; Vogelstein, Bert; Kinzler, Kenneth W.

    2008-02-05

    The human MSH2 gene, responsible for hereditary non-polyposis colorectal cancer, was identified by virtue of its homology to the MutS class of genes, which are involved in DNA mismatch repair. The sequence of cDNA clones of the human gene are provided, and the sequence of the gene can be used to demonstrate the existence of germ line mutations in hereditary non-polyposis colorectal cancer (HNPCC) kindreds, as well as in replication error.sup.+ (RER.sup.+) tumor cells.

  6. What is the relationship between ultraviolet B and global incidence rates of colorectal cancer?

    PubMed Central

    Cuomo, Raphael E.; Mohr, Sharif B.; Gorham, Edward D.; Garland, Cedric F.

    2013-01-01

    The purpose of this study is to examine the relationship between ultraviolet B and global incidence of colorectal cancer, while controlling for relevant covariates. Linear regression was used to assess the relationship between latitude and incidence rates of colon cancer in 173 countries. Multiple linear regression was employed to investigate the relationship between ultraviolet B dose and colorectal cancer rates while controlling for per capita intake of energy from animal sources, per capita health expenditure, pigmentation, and life expectancy. Data on all variables were available for 139 countries. Incidence of colon cancer was highest in countries distant from the equator (R2 = 0.50, p < 0.0001). UV B dose (p < 0.0001) was independently, inversely associated with incidence rates of colorectal cancer after controlling for intake of energy from animal sources, per capita health expenditure, pigmentation, and life expectancy (R2 for overall model = 0.76, p < 0.0001). Consistent with previous research, UVB was inversely associated with incidence of colon cancer. Further research on vitamin D and prevention of colon cancer in individuals should be conducted, including studies of higher serum 25-hydroxyvitamin D concentrations than have been studied to date. PMID:24494052

  7. American Cancer Society Colorectal Cancer Survivorship Care Guidelines.

    PubMed

    El-Shami, Khaled; Oeffinger, Kevin C; Erb, Nicole L; Willis, Anne; Bretsch, Jennifer K; Pratt-Chapman, Mandi L; Cannady, Rachel S; Wong, Sandra L; Rose, Johnie; Barbour, April L; Stein, Kevin D; Sharpe, Katherine B; Brooks, Durado D; Cowens-Alvarado, Rebecca L

    2015-01-01

    Colorectal cancer (CRC) is the third most common cancer and third leading cause of cancer death in both men and women and second leading cause of cancer death when men and women are combined in the United States (US). Almost two-thirds of CRC survivors are living 5 years after diagnosis. Considering the recent decline in both incidence and mortality, the prevalence of CRC survivors is likely to increase dramatically over the coming decades with the increase in rates of CRC screening, further advances in early detection and treatment and the aging and growth of the US population. Survivors are at risk for a CRC recurrence, a new primary CRC, other cancers, as well as both short-term and long-term adverse effects of the CRC and the modalities used to treat it. CRC survivors may also have psychological, reproductive, genetic, social, and employment concerns after treatment. Communication and coordination of care between the treating oncologist and the primary care clinician is critical to effectively and efficiently manage the long-term care of CRC survivors. The guidelines in this article are intended to assist primary care clinicians in delivering risk-based health care for CRC survivors who have completed active therapy. PMID:26348643

  8. American Cancer Society Colorectal Cancer Survivorship Care Guidelines.

    PubMed

    El-Shami, Khaled; Oeffinger, Kevin C; Erb, Nicole L; Willis, Anne; Bretsch, Jennifer K; Pratt-Chapman, Mandi L; Cannady, Rachel S; Wong, Sandra L; Rose, Johnie; Barbour, April L; Stein, Kevin D; Sharpe, Katherine B; Brooks, Durado D; Cowens-Alvarado, Rebecca L

    2015-01-01

    Colorectal cancer (CRC) is the third most common cancer and third leading cause of cancer death in both men and women and second leading cause of cancer death when men and women are combined in the United States (US). Almost two-thirds of CRC survivors are living 5 years after diagnosis. Considering the recent decline in both incidence and mortality, the prevalence of CRC survivors is likely to increase dramatically over the coming decades with the increase in rates of CRC screening, further advances in early detection and treatment and the aging and growth of the US population. Survivors are at risk for a CRC recurrence, a new primary CRC, other cancers, as well as both short-term and long-term adverse effects of the CRC and the modalities used to treat it. CRC survivors may also have psychological, reproductive, genetic, social, and employment concerns after treatment. Communication and coordination of care between the treating oncologist and the primary care clinician is critical to effectively and efficiently manage the long-term care of CRC survivors. The guidelines in this article are intended to assist primary care clinicians in delivering risk-based health care for CRC survivors who have completed active therapy.

  9. Natural Product Shows Effectiveness in Combating Colorectal Cancer | Poster

    Cancer.gov

    An herbal extract used for centuries to prevent heart disease has now been shown to be effective against colorectal cancer when tested in laboratory cell cultures. Scientists from NCI at Frederick found that the natural extract cryptotanshinone (CPT) stops the uncontrolled cell growth characteristic of cancer by interfering with a protein that has been implicated in several cancers, including those of the colon and rectum. The results appear in the journal Molecular and Cellular Biochemistry.

  10. Fundamental Causes of Colorectal Cancer Mortality: The Implications of Informational Diffusion

    PubMed Central

    Wang, Andrew; Clouston, Sean AP; Rubin, Marcie S; Colen, Cynthia G; Link, Bruce G

    2012-01-01

    Context Colorectal cancer is a major cause of mortality in the United States, with 52,857 deaths estimated in 2012. To explore further the social inequalities in colorectal cancer mortality, we used fundamental cause theory to consider the role of societal diffusion of information and socioeconomic status. Methods We used the number of deaths from colorectal cancer in U.S. counties between 1968 and 2008. Through geographical mapping, we examined disparities in colorectal cancer mortality as a function of socioeconomic status and the rate of diffusion of information. In addition to providing year-specific trends in colorectal cancer mortality rates, we analyzed these data using negative binomial regression. Findings The impact of socioeconomic status (SES) on colorectal cancer mortality is substantial, and its protective impact increases over time. Equally important is the impact of informational diffusion on colorectal cancer mortality over time. However, while the impact of SES remains significant when concurrently considering the role of diffusion of information, the propensity for faster diffusion moderates its effect on colorectal cancer mortality. Conclusions The faster diffusion of information reduces both colorectal cancer mortality and inequalities in colorectal cancer mortality, although it was not sufficient to eliminate SES inequalities. These findings have important long-term implications for policymakers looking to reduce social inequalities in colorectal cancer mortality and other, related, preventable diseases. PMID:22985282

  11. Perspectives of colorectal cancer risk and screening among Dominicans and Puerto Ricans: stigma and misperceptions.

    PubMed

    Goldman, Roberta E; Diaz, Joseph A; Kim, Ivone

    2009-11-01

    Colorectal cancer is the second most common cancer among Latinos, but a lower percentage of Latinos are screened than Whites and Blacks. Along with recognized economic barriers, differences in knowledge and perceptions might impede colorectal screening among Latinos. We conducted 147 individual, qualitative interviews with Dominicans and Puerto Ricans in the northeastern United States to explore their explanatory models for colorectal cancer and screening barriers. Many participants had not previously heard of colorectal cancer. The most commonly mentioned cause of colorectal cancer was anal sex. Also considered risks were "bad food," digestion leading to constipation, and strained bowel movements. Screening barriers included stigma, misperceptions, embarrassment, and machismo. Progress toward increasing colorectal cancer screening requires normalization of this screening among Latinos. Higher patient familiarity, along with improved physician counseling and referral, might contribute to reducing stigma and other barriers, and to enhancing knowledge and Latino community support of colorectal cancer screening.

  12. Determining the familial risk distribution of colorectal cancer: a data mining approach.

    PubMed

    Chau, Rowena; Jenkins, Mark A; Buchanan, Daniel D; Ait Ouakrim, Driss; Giles, Graham G; Casey, Graham; Gallinger, Steven; Haile, Robert W; Le Marchand, Loic; Newcomb, Polly A; Lindor, Noralane M; Hopper, John L; Win, Aung Ko

    2016-04-01

    This study was aimed to characterize the distribution of colorectal cancer risk using family history of cancers by data mining. Family histories for 10,066 colorectal cancer cases recruited to population cancer registries of the Colon Cancer Family Registry were analyzed using a data mining framework. A novel index was developed to quantify familial cancer aggregation. Artificial neural network was used to identify distinct categories of familial risk. Standardized incidence ratios (SIRs) and corresponding 95% confidence intervals (CIs) of colorectal cancer were calculated for each category. We identified five major, and 66 minor categories of familial risk for developing colorectal cancer. The distribution the major risk categories were: (1) 7% of families (SIR = 7.11; 95% CI 6.65-7.59) had a strong family history of colorectal cancer; (2) 13% of families (SIR = 2.94; 95% CI 2.78-3.10) had a moderate family history of colorectal cancer; (3) 11% of families (SIR = 1.23; 95% CI 1.12-1.36) had a strong family history of breast cancer and a weak family history of colorectal cancer; (4) 9 % of families (SIR = 1.06; 95 % CI 0.96-1.18) had strong family history of prostate cancer and weak family history of colorectal cancer; and (5) 60% of families (SIR = 0.61; 95% CI 0.57-0.65) had a weak family history of all cancers. There is a wide variation of colorectal cancer risk that can be categorized by family history of cancer, with a strong gradient of colorectal cancer risk between the highest and lowest risk categories. The risk of colorectal cancer for people with the highest risk category of family history (7% of the population) was 12-times that for people in the lowest risk category (60%) of the population. Data mining was proven an effective approach for gaining insight into the underlying cancer aggregation patterns and for categorizing familial risk of colorectal cancer.

  13. Family history characteristics, tumor microsatellite instability and germline MSH2 and MLH1 mutations in hereditary colorectal cancer.

    PubMed

    Bapat, B V; Madlensky, L; Temple, L K; Hiruki, T; Redston, M; Baron, D L; Xia, L; Marcus, V A; Soravia, C; Mitri, A; Shen, W; Gryfe, R; Berk, T; Chodirker, B N; Cohen, Z; Gallinger, S

    1999-02-01

    Recent characterization of the molecular genetic basis of hereditary nonpolyposis colorectal cancer provides an important opportunity for identification of individuals and their families with germline mutations in mismatch repair genes. Cancer family history criteria that accurately define hereditary colorectal cancer are necessary for cost-effective testing for germline mutations in mismatch repair genes. The present report describes the results of analysis of 33 colorectal cancer cases/families that satisfy our modified family history criteria (Mount Sinai criteria) for colorectal cancer. Fourteen of these families met the more stringent Amsterdam criteria. Germline MSH2 and MLH1 mutations were identified by the reverse transcription-polymerase chain reaction and the protein truncation test, and confirmed by sequencing. Microsatellite instability analysis was performed on available tumors from affected patients. MSH2 or MLH1 mutations were detected in 8 of 14 Amsterdam criteria families and in 5 of the remaining 19 cases/families that only satisfied the Mount Sinai criteria. Three of the latter families had features of the Muir-Torre syndrome. A high level of microsatellite instability (MSI-H) was detected in almost all (16/18) colorectal cancers from individuals with MSH2 and MLH1 mutations, and infrequently (1/21) in colorectal cancer specimens from cases without detectable mutations. Families with germline MSH2 and MLH1 mutations tended to have individuals affected at younger ages and with multiple tumors. The Amsterdam criteria are useful, but not sufficient, for detecting hereditary colorectal cancer families with germline MSH2 and MLH1 mutations, since a proportion of cases and families with mutations in mismatch repair genes will be missed. Further development of cancer family history criteria are needed, using unbiased prospectively collected cases, to define more accurately those who will benefit from MSH2 and MLH1 mutation analysis. PMID:10190329

  14. Pharmacological cyclin dependent kinase inhibitors: Implications for colorectal cancer

    PubMed Central

    Balakrishnan, Archana; Vyas, Arpita; Deshpande, Kaivalya; Vyas, Dinesh

    2016-01-01

    Colorectal cancer accounts for a significant proportion of cancer deaths worldwide. The need to develop more chemotherapeutic agents to combat this disease is critical. Cyclin dependent kinases (CDKs), along with its binding partner cyclins, serve to control the growth of cells through the cell cycle. A new class of drugs, termed CDK inhibitors, has been studied in preclinical and now clinical trials. These inhibitors are believed to act as an anti-cancer drug by blocking CDKs to block the uncontrolled cellular proliferation that is hallmark of cancers like colorectal cancer. CDK article provides overview of the emerging drug class of CDK inhibitors and provides a list of ones that are currently in clinical trials. PMID:26900281

  15. Pathology Features in Bethesda Guidelines Predict Colorectal Cancer Microsatellite Instability: A Population-Based Study

    PubMed Central

    Jenkins, Mark A.; Hayashi, Shinichi; O’shea, Anne-Marie; Burgart, Lawrence J.; Smyrk, Tom C.; Shimizu, David; Waring, Paul M.; Ruszkiewicz, Andrew R.; Pollett, Aaron F.; Redston, Mark; Barker, Melissa A.; Baron, John A.; Casey, Graham R.; Dowty, James G.; Giles, Graham G.; Limburg, Paul; Newcomb, Polly; Young, Joanne P.; Walsh, Michael D.; Thibodeau, Stephen N.; Lindor, Noralane M.; Lemarchand, Loïc; Gallinger, Steven; Haile, Robert W.; Potter, John D.; Hopper, John L.; Jass, Jeremy R.

    2010-01-01

    Background & Aims The revised Bethesda guidelines for Lynch syndrome recommend microsatellite instability (MSI) testing all colorectal cancers in patients diagnosed before age 50 years and colorectal cancers diagnosed in patients between ages 50 and 59 years with particular pathology features. Our aim was to identify pathology and other features that independently predict high MSI (MSI-H). Methods Archival tissue from 1098 population-based colorectal cancers diagnosed before age 60 years was tested for MSI. Pathology features, site, and age at diagnosis were obtained. Multiple logistic regression was performed to determine the predictive value of each feature, as measured by an odds ratio (OR), from which a scoring system (MsPath) was developed to estimate the probability a colorectal cancer is MSI-H. Results Fifteen percent of tumors (162) were MSI-H. Independent predictors were tumor-infiltrating lymphocytes (OR, 9.1; 95% confidence interval [CI], 5.9 –14.1), proximal subsite (OR, 4.7; 95% CI, 3.1–7.3), mucinous histology (OR, 2.8; 95% CI, 1.7– 4.8), poor differentiation (OR, 1.9; 95% CI, 1.2–3.1), Crohn’s-like reaction (OR, 1.9; 95% CI, 1.2–2.9), and diagnosis before age 50 years (OR, 1.9; 95% CI, 1.3–2.9). MsPath score ≥ 1.0 had a sensitivity of 93% and a specificity of 55% for MSI-H. Conclusions The probability an individual colorectal cancer is MSI-H is predicted well by the MsPath score. There is little value in testing for DNA mismatch repair loss in tumors, or for germline mismatch repair mutations, for colorectal cancers diagnosed in patients before age 60 years with an MSPath score <1 (approximately 50%). Pathology can identify almost all MSI-H colorectal cancers diagnosed before age 60 years. PMID:17631130

  16. Colorectal cancer surveillance in inflammatory bowel disease: The search continues

    PubMed Central

    Ahmadi, Anis; Polyak, Steven; Draganov, Peter V

    2009-01-01

    Patients with inflammatory bowel disease (IBD) are at increased risk for colorectal cancer (CRC). Risk factors for the development of CRC in the setting of IBD include disease duration, anatomic extent of disease, age at time of diagnosis, severity of inflammation, family history of colon cancer, and concomitant primary sclerosing cholangitis. The current surveillance strategy of surveillance colonoscopy with multiple random biopsies most likely reduces morbidity and mortality associated with IBD-related CRC. Unfortunately, surveillance colonoscopy also has severe limitations including high cost, sampling error at time of biopsy, and interobserver disagreement in histologically grading dysplasia. Furthermore, once dysplasia is detected there is disagreement about its management. Advances in endoscopic imaging techniques are already underway, and may potentially aid in dysplasia detection and improve overall surveillance outcomes. Management of dysplasia depends predominantly on the degree and focality of dysplasia, with the mainstay of management involving either proctocolectomy or continued colonoscopic surveillance. Lastly, continued research into additional chemopreventive agents may increase our arsenal in attempting to reduce the incidence of IBD-associated CRC. PMID:19115469

  17. Excessive collagen turnover products are released during colorectal cancer progression and elevated in serum from metastatic colorectal cancer patients.

    PubMed

    Kehlet, S N; Sanz-Pamplona, R; Brix, S; Leeming, D J; Karsdal, M A; Moreno, V

    2016-01-01

    During cancer progression, the homeostasis of the extracellular matrix becomes imbalanced with an excessive collagen remodeling by matrix metalloproteinases. As a consequence, small protein fragments of degraded collagens are released into the circulation. We have investigated the potential of protein fragments of collagen type I, III and IV as novel biomarkers for colorectal cancer. Specific fragments of degraded type I, III and IV collagen (C1M, C3M, C4M) and type III collagen formation (Pro-C3) were assessed in serum from colorectal cancer patients, subjects with adenomas and matched healthy controls using well-characterized and validated ELISAs. Serum levels of the biomarkers were significantly elevated in colorectal cancer patients compared to subjects with adenomas (C1M, Pro-C3, C3M) and controls (C1M, Pro-C3). When patients were stratified according to their tumour stage, all four biomarkers were able to differentiate stage IV metastatic patients from all other stages. Combination of all markers with age and gender in a logistic regression model discriminated between metastatic and non-metastatic patients with an AUROC of 0.80. The data suggest that the levels of these collagen remodeling biomarkers may be a measure of tumour activity and invasiveness and may provide new clinical tools for monitoring of patients with advanced stage colorectal cancer. PMID:27465284

  18. Excessive collagen turnover products are released during colorectal cancer progression and elevated in serum from metastatic colorectal cancer patients

    PubMed Central

    Kehlet, S. N.; Sanz-Pamplona, R.; Brix, S.; Leeming, D. J.; Karsdal, M. A.; Moreno, V.

    2016-01-01

    During cancer progression, the homeostasis of the extracellular matrix becomes imbalanced with an excessive collagen remodeling by matrix metalloproteinases. As a consequence, small protein fragments of degraded collagens are released into the circulation. We have investigated the potential of protein fragments of collagen type I, III and IV as novel biomarkers for colorectal cancer. Specific fragments of degraded type I, III and IV collagen (C1M, C3M, C4M) and type III collagen formation (Pro-C3) were assessed in serum from colorectal cancer patients, subjects with adenomas and matched healthy controls using well-characterized and validated ELISAs. Serum levels of the biomarkers were significantly elevated in colorectal cancer patients compared to subjects with adenomas (C1M, Pro-C3, C3M) and controls (C1M, Pro-C3). When patients were stratified according to their tumour stage, all four biomarkers were able to differentiate stage IV metastatic patients from all other stages. Combination of all markers with age and gender in a logistic regression model discriminated between metastatic and non-metastatic patients with an AUROC of 0.80. The data suggest that the levels of these collagen remodeling biomarkers may be a measure of tumour activity and invasiveness and may provide new clinical tools for monitoring of patients with advanced stage colorectal cancer. PMID:27465284

  19. Whole grain intake and survival among Scandinavian colorectal cancer patients.

    PubMed

    Skeie, Guri; Braaten, Tonje; Olsen, Anja; Kyrø, Cecilie; Tjønneland, Anne; Nilsson, Lena Maria; Landberg, Rikard; Lund, Eiliv

    2014-01-01

    To our knowledge, no studies of associations between intake of whole grain (WHG) and survival of colorectal cancer have been published, despite evidence that dietary fiber, and to some extent WHG, are associated with lower risk of colorectal cancer. Scandinavia is an area where the WHG consumption traditionally is high. We performed a case-only (N = 1119) study in the Scandinavian HELGA cohort of pre-diagnosis WHG intake (total WHG, WHG wheat, WHG rye, and WHG oats) and survival of colorectal cancer. Cox regression analyses were used to study the associations, both in categorical and continuous models, stratified by location (proximal, distal, rectum) and country. No evidence of an association was found, neither for total WHG intake (hazard ratio = 1.32, 95% confidence interval: 0.88-1.97 lowest vs. highest tertile, adjusted for age at diagnosis, metastasis status, smoking, folate, margarine, and energy), nor for specific grains. Prediagnosis consumption of WHG does not seem to improve survival of colorectal cancer in subjects diagnosed within this prospective population-based Scandinavian cohort.

  20. Restaging of colorectal cancer and PET/CT

    PubMed Central

    Çınar, Alev; Gençoğlu, Esra Arzu; Korkmaz, Meliha

    2013-01-01

    Positron Emission Tomography/Computerized Tomography (PET/CT) is an important assessment method in restaging of oncology patients. Its ability to detect the metabolic/functional changes in patients with colorectal cancer during the early stages, in which morphological changes cannot be documented, is significantly superior to other imaging modalities. PMID:25931851

  1. Internet Use for Prediagnosis Symptom Appraisal by Colorectal Cancer Patients

    ERIC Educational Resources Information Center

    Thomson, Maria D.; Siminoff, Laura A.; Longo, Daniel R.

    2012-01-01

    Background: This study explored the characteristics of colorectal cancer (CRC) patients who accessed Internet-based health information as part of their symptom appraisal process prior to consulting a health care provider. Method: Newly diagnosed CRC patients who experienced symptoms prior to diagnosis were interviewed. Brief COPE was used to…

  2. Potential role of probiotics on colorectal cancer prevention

    PubMed Central

    2012-01-01

    Background Colorectal cancer represents the most common malignancy of the gastrointestinal tract. Owing to differences in dietary habits and lifestyle, this neoplasm is more common in industrialized countries than in developing ones. Evidence from a wide range of sources supports the assumption that the link between diet and colorectal cancer may be due to an imbalance of the intestinal microflora. Discussion Probiotic bacteria are live microorganisms that, when administered in adequate amounts, confer a healthy benefit on the host, and they have been investigated for their protective anti-tumor effects. In vivo and molecular studies have displayed encouraging findings that support a role of probiotics in colorectal cancer prevention. Summary Several mechanisms could explain the preventive action of probiotics against colorectal cancer onset. They include: alteration of the intestinal microflora; inactivation of cancerogenic compounds; competition with putrefactive and pathogenic microbiota; improvement of the host’s immune response; anti-proliferative effects via regulation of apoptosis and cell differentiation; fermentation of undigested food; inhibition of tyrosine kinase signaling pathways. PMID:23173670

  3. BRAF inhibitors in colorectal cancer: Toward a differentiation therapy?

    PubMed Central

    Herr, Ricarda; Brummer, Tilman

    2015-01-01

    BRAF inhibitor monotherapy appears to be ineffective in BRAFV600E-positive colorectal cancer (CRC) as a result of inherent EGFR-mediated resistance mechanisms. This concept initiated combinatorial treatment approaches. Nevertheless, BRAF inhibition in isogenic CRC cell lines induced enhanced cell-cell adhesion and differentiation, underlining a potential benefit of BRAF inhibitors in CRC. PMID:27308494

  4. Multi Texture Analysis of Colorectal Cancer Continuum Using Multispectral Imagery

    PubMed Central

    Chaddad, Ahmad; Desrosiers, Christian; Bouridane, Ahmed; Toews, Matthew; Hassan, Lama; Tanougast, Camel

    2016-01-01

    Purpose This paper proposes to characterize the continuum of colorectal cancer (CRC) using multiple texture features extracted from multispectral optical microscopy images. Three types of pathological tissues (PT) are considered: benign hyperplasia, intraepithelial neoplasia and carcinoma. Materials and Methods In the proposed approach, the region of interest containing PT is first extracted from multispectral images using active contour segmentation. This region is then encoded using texture features based on the Laplacian-of-Gaussian (LoG) filter, discrete wavelets (DW) and gray level co-occurrence matrices (GLCM). To assess the significance of textural differences between PT types, a statistical analysis based on the Kruskal-Wallis test is performed. The usefulness of texture features is then evaluated quantitatively in terms of their ability to predict PT types using various classifier models. Results Preliminary results show significant texture differences between PT types, for all texture features (p-value < 0.01). Individually, GLCM texture features outperform LoG and DW features in terms of PT type prediction. However, a higher performance can be achieved by combining all texture features, resulting in a mean classification accuracy of 98.92%, sensitivity of 98.12%, and specificity of 99.67%. Conclusions These results demonstrate the efficiency and effectiveness of combining multiple texture features for characterizing the continuum of CRC and discriminating between pathological tissues in multispectral images. PMID:26901134

  5. A preventive registry for hereditary nonpolyposis colorectal cancer.

    PubMed

    Madlensky, L; Berk, T C; Bapat, B V; McLeod, R S; Couture, J; Baron, D; Hiruki, T; Redston, M; Cohen, Z; Gallinger, S

    1995-07-01

    Hereditary nonpolyposis colorectal cancer (HNPCC) is a genetic disorder characterized by a strong family history of colorectal and extracolonic cancers, usually at a young age. This article presents a new provincial service for families with HNPCC. The Steve Atanas Stavro Familial Gastrointestinal Cancer Registry at Mount Sinai Hospital is accruing patients that meet a set of criteria establishing a putative diagnosis of HNPCC. The objectives of the Registry are to develop and assess patient pedigrees, to coordinate screening procedures for at-risk persons, to maintain a prospective database of patient information, to provide education and support for families and to contribute to research. To date, surgeons and patients are the most common referral sources, while oncologists and geneticists are the least common. The ultimate goal of the HNPCC service is the secondary prevention of cancer and a corresponding decrease in mortality for HNPCC family members. PMID:8853507

  6. Colorectal Cancer and the Human Gut Microbiome: Reproducibility with Whole-Genome Shotgun Sequencing

    PubMed Central

    Hua, Xing; Zeller, Georg; Sunagawa, Shinichi; Voigt, Anita Y.; Hercog, Rajna; Goedert, James J.; Shi, Jianxin; Bork, Peer; Sinha, Rashmi

    2016-01-01

    Accumulating evidence indicates that the gut microbiota affects colorectal cancer development, but previous studies have varied in population, technical methods, and associations with cancer. Understanding these variations is needed for comparisons and for potential pooling across studies. Therefore, we performed whole-genome shotgun sequencing on fecal samples from 52 pre-treatment colorectal cancer cases and 52 matched controls from Washington, DC. We compared findings from a previously published 16S rRNA study to the metagenomics-derived taxonomy within the same population. In addition, metagenome-predicted genes, modules, and pathways in the Washington, DC cases and controls were compared to cases and controls recruited in France whose specimens were processed using the same platform. Associations between the presence of fecal Fusobacteria, Fusobacterium, and Porphyromonas with colorectal cancer detected by 16S rRNA were reproduced by metagenomics, whereas higher relative abundance of Clostridia in cancer cases based on 16S rRNA was merely borderline based on metagenomics. This demonstrated that within the same sample set, most, but not all taxonomic associations were seen with both methods. Considering significant cancer associations with the relative abundance of genes, modules, and pathways in a recently published French metagenomics dataset, statistically significant associations in the Washington, DC population were detected for four out of 10 genes, three out of nine modules, and seven out of 17 pathways. In total, colorectal cancer status in the Washington, DC study was associated with 39% of the metagenome-predicted genes, modules, and pathways identified in the French study. More within and between population comparisons are needed to identify sources of variation and disease associations that can be reproduced despite these variations. Future studies should have larger sample sizes or pool data across studies to have sufficient power to detect

  7. Colorectal cancer in a nuclear family. Familial or hereditary?

    PubMed

    Lynch, H T; Fitzgibbons, R; Marcus, J; McGill, J; Voorhees, G J; Lynch, J F

    1985-05-01

    Because of the high incidence of colorectal cancer, familial aggregations of this disease are common. Differentiation between etiologies contributing to familial clustering (which may have resulted either from common environmental exposure or from mere chance) and primary genetic factors may prove vexing to the physician. This report deals with the myriad problems encountered when attempting to make such etiologic distinctions in order to provide appropriate surveillance and management, based upon tumor spectrum and natural history, for patients at increased cancer risk.

  8. Identification of a biomarker panel for colorectal cancer diagnosis

    PubMed Central

    2012-01-01

    Background Malignancies arising in the large bowel cause the second largest number of deaths from cancer in the Western World. Despite progresses made during the last decades, colorectal cancer remains one of the most frequent and deadly neoplasias in the western countries. Methods A genomic study of human colorectal cancer has been carried out on a total of 31 tumoral samples, corresponding to different stages of the disease, and 33 non-tumoral samples. The study was carried out by hybridisation of the tumour samples against a reference pool of non-tumoral samples using Agilent Human 1A 60-mer oligo microarrays. The results obtained were validated by qRT-PCR. In the subsequent bioinformatics analysis, gene networks by means of Bayesian classifiers, variable selection and bootstrap resampling were built. The consensus among all the induced models produced a hierarchy of dependences and, thus, of variables. Results After an exhaustive process of pre-processing to ensure data quality--lost values imputation, probes quality, data smoothing and intraclass variability filtering--the final dataset comprised a total of 8, 104 probes. Next, a supervised classification approach and data analysis was carried out to obtain the most relevant genes. Two of them are directly involved in cancer progression and in particular in colorectal cancer. Finally, a supervised classifier was induced to classify new unseen samples. Conclusions We have developed a tentative model for the diagnosis of colorectal cancer based on a biomarker panel. Our results indicate that the gene profile described herein can discriminate between non-cancerous and cancerous samples with 94.45% accuracy using different supervised classifiers (AUC values in the range of 0.997 and 0.955). PMID:22280244

  9. Serrated colorectal cancer: Molecular classification, prognosis, and response to chemotherapy

    PubMed Central

    Murcia, Oscar; Juárez, Miriam; Hernández-Illán, Eva; Egoavil, Cecilia; Giner-Calabuig, Mar; Rodríguez-Soler, María; Jover, Rodrigo

    2016-01-01

    Molecular advances support the existence of an alternative pathway of colorectal carcinogenesis that is based on the hypermethylation of specific DNA regions that silences tumor suppressor genes. This alternative pathway has been called the serrated pathway due to the serrated appearance of tumors in histological analysis. New classifications for colorectal cancer (CRC) were proposed recently based on genetic profiles that show four types of molecular alterations: BRAF gene mutations, KRAS gene mutations, microsatellite instability, and hypermethylation of CpG islands. This review summarizes what is known about the serrated pathway of CRC, including CRC molecular and clinical features, prognosis, and response to chemotherapy. PMID:27053844

  10. Mutation profiles of synchronous colorectal cancers from a patient with Lynch syndrome suggest distinct oncogenic pathways

    PubMed Central

    Shi, Chanjuan; Holt, Jonathan A.; Vnencak-Jones, Cindy L.

    2016-01-01

    Patients with Lynch syndrome often present with multiple synchronous or metachronous colorectal cancers (CRCs). The presence of multiple CRCs with distinct genetic profiles and driver mutations could complicate treatment as each cancer may respond differently to therapy. Studies of sporadic CRCs suggested that synchronous tumors have distinct etiologies, but could not rule out differences in genetic background. The presence of multiple cancers in a patient with a predisposing mutation provides an opportunity to profile synchronous cancers in the same genetic background. Here, we describe the case of a patient with Lynch syndrome that presented with six synchronous CRCs. Microsatellite instability (MSI) and genomic profiling indicated that each lesion had a unique pattern of instability and a distinct profile of affected genes. These findings support the idea that in Lynch syndrome, synchronous CRCs can develop in parallel with distinct mutation profiles and that these differences may inform treatment decisions. PMID:27284491

  11. Effect of Social Deprivation on the Stage and Mode of Presentation of Colorectal Cancer

    PubMed Central

    Ashford-Wilson, Sarah; Brown, Stephanie; Pal, Atanu; Lal, Roshan; Aryal, Kamal

    2016-01-01

    Purpose Based in a hospital serving one of the most deprived areas in the United Kingdom (UK), we aimed to investigate, using the Indices of Deprivation 2010, the hypothesis that deprivation affects the stage and mode of presentation of colorectal cancer. Methods All newly diagnosed patients with colorectal cancer presenting to a District General Hospital in the UK between January 2010 and December 2014 were included. Data were collected from the Somerset National Cancer Database. The effect of social deprivation, measured using the Index of Multiple Deprivation Score, on the stage and mode of presentation was evaluated utilizing Microsoft Excel and IBM SPSS ver. 22.0. Results A total of 701 patients (54.5% male; mean age, 76 years) were included; 534 (76.2%) underwent a surgical procedure, and 497 (70.9%) underwent a colorectal resection. Of the patients undergoing a colorectal resection, 86 (17.3%) had an emergency surgical resection. Social deprivation was associated with Duke staging (P = 0.09). The 90-day mortality in patients undergoing emergency surgery was 12.8% compared to 6.8% in patients undergoing elective surgery (P = 0.06). No association was found between deprivation and emergency presentation (P = 0.97). A logistic regression analysis showed no increase in the probability of metastasis amongst deprived patients. Conclusion This study suggests an association between deprivation and the stage of presentation of colorectal cancer. Patients undergoing emergency surgery tend to have a higher 90-day mortality rate, although this was not related to deprivation. This study highlights the need to develop an individual measure to assess social deprivation. PMID:27626022

  12. Spontaneous initiation, promotion and progression of colorectal cancer in the novel A/J Min/+ mouse.

    PubMed

    Sødring, Marianne; Gunnes, Gjermund; Paulsen, Jan Erik

    2016-04-15

    The C57BL/6J multiple intestinal neoplasia (Min/+) mouse is a widely used murine model for familial adenomatous polyposis, a hereditary form of human colorectal cancer. However, it is a questionable model partly because the vast majority of tumors arise in the small intestine, and partly because the fraction of tumors that progress to invasive carcinomas is minuscule. A/J mice are typically more susceptible to carcinogen-induced colorectal cancer than C57BL/6J mice. To investigate whether the novel Min/+ mouse on the A/J genetic background could be a better model for colorectal cancer, we examined the spontaneous intestinal tumorigenesis in 81 A/J Min/+ mice ranging in age from 4 to 60 weeks. The A/J Min/+ mouse exhibited a dramatic increase in number of colonic lesions when compared to what has been reported for the conventional Min/+ mouse; however, an increase in small intestinal lesions did not occur. In addition, this novel mouse model displayed a continual development of colonic lesions highlighted by the transition from early lesions (flat ACF) to tumors over time. In mice older than 40 weeks, 13 colonic (95% CI: 8.7-16.3) and 21 small intestinal (95% CI: 18.6-24.3) tumors were recorded. Notably, a considerable proportion of those lesions progressed to carcinomas in both the colon (21%) and small intestine (51%). These findings more closely reflect aspects of human colorectal carcinogenesis. In conclusion, the novel A/J Min/+ mouse may be a relevant model for initiation, promotion and progression of colorectal cancer.

  13. Effect of Social Deprivation on the Stage and Mode of Presentation of Colorectal Cancer

    PubMed Central

    Ashford-Wilson, Sarah; Brown, Stephanie; Pal, Atanu; Lal, Roshan; Aryal, Kamal

    2016-01-01

    Purpose Based in a hospital serving one of the most deprived areas in the United Kingdom (UK), we aimed to investigate, using the Indices of Deprivation 2010, the hypothesis that deprivation affects the stage and mode of presentation of colorectal cancer. Methods All newly diagnosed patients with colorectal cancer presenting to a District General Hospital in the UK between January 2010 and December 2014 were included. Data were collected from the Somerset National Cancer Database. The effect of social deprivation, measured using the Index of Multiple Deprivation Score, on the stage and mode of presentation was evaluated utilizing Microsoft Excel and IBM SPSS ver. 22.0. Results A total of 701 patients (54.5% male; mean age, 76 years) were included; 534 (76.2%) underwent a surgical procedure, and 497 (70.9%) underwent a colorectal resection. Of the patients undergoing a colorectal resection, 86 (17.3%) had an emergency surgical resection. Social deprivation was associated with Duke staging (P = 0.09). The 90-day mortality in patients undergoing emergency surgery was 12.8% compared to 6.8% in patients undergoing elective surgery (P = 0.06). No association was found between deprivation and emergency presentation (P = 0.97). A logistic regression analysis showed no increase in the probability of metastasis amongst deprived patients. Conclusion This study suggests an association between deprivation and the stage of presentation of colorectal cancer. Patients undergoing emergency surgery tend to have a higher 90-day mortality rate, although this was not related to deprivation. This study highlights the need to develop an individual measure to assess social deprivation.

  14. Serrated and non-serrated precursor lesions of colorectal cancer.

    PubMed

    Langner, Cord

    2015-01-01

    Although often viewed as a single disease, colorectal cancer more accurately represents a family of diseases with different precursor lesions. Conventional (tubular, tubulovillous and villous) adenomas are the most common neoplastic lesions occurring in the large intestine. They have adenomatous polyposis coli (APC) mutations and arise from dysplastic aberrant crypt foci, initially as polyclonal lesions. In sporadic tumours, neoplastic progression follows the traditional pathway (chromosomal instability pathway), resulting in CpG island methylator phenotype (CIMP)-negative, microsatellite-stable (MSS), BRAF and KRAS wild-type cancers. Germline mutations in the APC gene lead to familial adenomatous polyposis. Conventional adenomas are also the precursors of Lynch syndrome-associated microsatellite-instable (MSI-high) cancers. Sessile serrated adenoma/polyp (SSA/P) is the principal precursor lesion of the serrated pathway, in which BRAF mutation can lead to colorectal cancer with MSI-high CIMP-high or MSS CIMP-high phenotype. SSA/Ps have been associated with synchronous and metachronous invasive adenocarcinomas as well as so-called interval carcinomas. Serrated polyposis is rare but most likely underdiagnosed. Affected individuals bear an increased but unspecified risk for the development of colorectal cancer; close endoscopic surveillance is warranted. Traditional serrated adenomas (TSAs) are much less common than the other serrated lesions. Cancers originating from TSAs may show KRAS mutation with a CIMP-high MSS phenotype.

  15. [Genetics of Colorectal Tumorigenesis (Possibilities of Testing and Screening Prediction of Hereditary Form of Colorectal Cancer--Lynch Syndrome)].

    PubMed

    Mľkva, I

    2016-01-01

    Colorectal cancer is currently one of the most frequent cancers in developed countries. Understanding the molecular principles of its pathogenesis has recently come into focus of many oncogenetic studies. Colorectal cancer also represents an ideal model for the study of molecular basis of cancerogenesis owing to the wide availability of its precursor lesions and the existence of several notorious genetic predispositions such as familial adenomatous polyposis and Lynch syndrome. The classical model of colorectal tumorigenesis, described by Fearon and Vogelstein, suggested the idea of a conventional progression from adenoma to carcinoma. It was based on a careful analysis of mutations occurring within particular stages of carcinogenesis with regards to their stepwise accumulations leading to neoplastic transformation of the colonic epithelium. Recently, new evidence has pointed to an alternative model of colorectal tumorigenesis introducing the concept of serrated precursors. This alternative pathway, known as the serrated pathway, has provided a new perspective on colorectal cancer development. Nowadays, three molecular pathways leading to colorectal tumorigenesis are recognized: 1. the chromosomal instability pathway typified by familial adenomatous polyposis; 2. the mutator pathway characterized by inactivation of DNA mismatch repair genes such as in Lynch syndrome or a number of sporadic colorectal cancers; 3. the hypermethylation serrated neoplasia pathway characterized by excessive methylation of some CpG islands in the promoter region of certain genes (positive CpG islands methylator phenotype) (CIMP+).

  16. Colorectal cancer survivors undergoing genetic testing for hereditary non-polyposis colorectal cancer: motivational factors and psychosocial functioning.

    PubMed

    Esplen, M J; Madlensky, L; Aronson, M; Rothenmund, H; Gallinger, S; Butler, K; Toner, B; Wong, J; Manno, M; McLaughlin, J

    2007-11-01

    Hereditary non-polyposis colorectal cancer (HNPCC) represents about 1-3% of all cases of colorectal cancer (CRC). The objectives of the study were to examine motivational factors, expectations and psychosocial functioning in a sample of CRC survivors undergoing genetic testing for HNPCC. A cross-sectional survey of 314 colorectal cancer patients recruited through a population-based colon cancer family registry was conducted. Motivations for genetic testing for hereditary cancer were similar to those of clinic-based samples of CRC patients and included learning of the increased risk to offspring and finding out if additional screening was needed. While age at diagnosis and sex were associated with psychological functioning, significant predictors of post-counseling distress were perceived lower satisfaction with social support, an escape-avoidant coping style and the anticipation of becoming depressed if a mutation was present. Most cancer survivors anticipated disclosing test results to relatives and physicians. Cancer survivors reported several motivations for genetic testing for HNPCC that varied by sex. A subgroup of survivors with lower satisfaction with social support and an escape-avoidant coping style were worried about the potential impact of genetic test results and demonstrated more distress following counseling. Findings have implications for future research and potential support needs during the genetic counseling and testing process. PMID:17892499

  17. Colorectal Cancer-Associated Fibroblasts are Genotypically Distinct

    PubMed Central

    Mrazek, Amy A.; Carmical, Joseph R.; Wood, Thomas G.; Hellmich, Mark R.; Eltorky, Mahmoud; Bohanon, Frederick J.; Chao, Celia

    2014-01-01

    Cells in the stromal microenvironment facilitate colorectal cancer (CRC) progression and “co-evolve” with the epithelial cancer cells. Genetic and epigenetic differences between normal colorectal mucosa fibroblasts (NF) and carcinoma-associated fibroblasts (CAF) are not known. The aim of this study is to identify differentially expressed genes and promoter methylation between NF and CAF in human CRC. RNA and DNA were extracted from cultured NF and CAF from CRC resections. Genome-wide gene expression and methylation analyses were performed using the Illumina Human HT-12 v4.0 Expression and Illumina Human Methylation 27 BeadChips. Gene expression values between NF and CAF were compared and correlated with methylation patterns. Data was analyzed using Partek Genomics Suite using one-way ANOVA and p<0.05 as significant. Ingenuity iReport™ was performed to identify potential differences in biological functions and pathways between the NF and CAF. Paired methylation and gene expression analyses from 11 NF and 10 CAF colorectal samples are reported. Unsupervised analysis of differentially expressed genes using iReport™ identified “Top Diseases” as “Cancer” and “Colorectal Cancer”. Previous genome wide studies have focused on the cancer cells. We have identified differentially expressed genes and differentially methylated promoter regions that are CAF-specific in CRC. PMID:25530743

  18. Targeting colorectal cancer stem cells using curcumin and curcumin analogues: insights into the mechanism of the therapeutic efficacy.

    PubMed

    Ramasamy, Thamil Selvee; Ayob, Ain Zubaidah; Myint, Hsu Hsu Lynn; Thiagarajah, Sharmanee; Amini, Farahnaz

    2015-01-01

    Colorectal cancer is one of the commonest cancers in the world and it is also a common cause of cancer-related death worldwide. Despite advanced treatment strategies, the disease is rarely cured completely due to recurrence. Evidence shows that this is due to a small population of cells, called cancer stem cells (CSCs), in the tumour mass that have the self-renewal and differentiation potential to give rise to a new tumour population. Many pre-clinical and clinical studies have used curcumin and its analogues as anti-cancer agents in various types of cancer, including colorectal cancer. Intriguingly, curcumin and its analogues have also recently been shown to be effective in lowering tumour recurrence by targeting the CSC population, hence inhibiting tumour growth. In this review, we highlight the efficacy of curcumin and its analogues in targeting colorectal CSC and also the underlying molecular mechanism involved. Curcumin, in the presence or absence of other anti-cancer agents, has been shown to reduce the size of tumour mass and growth in both in vivo and in vitro studies by affecting many intracellular events that are associated with cancer progression and CSC formation. An insight into the molecular mechanism has unraveled the mode of action via which curcumin could affect the key regulators in CSC, importantly; (1) the signaling pathways, including Wnt/β-catenin, Sonic Hedgehog, Notch and PI3K/Akt/mTOR, (2) microRNA and (3) the epithelial-mesenchymal transition at multiple levels. Therefore, curcumin could play a role as chemosensitiser whereby the colorectal CSCs are now sensitised towards the anti-cancer therapy, therefore, combination therapy using anti-cancer agent with curcumin could be much more effective than treatment using a single cancer agent. This potential treatment modality can be further developed by employing an effective delivery system using a nanotechnology based approach to treat colorectal cancer. PMID:26457069

  19. Potential Protective Effects of Probiotics and Prebiotics Against Colorectal Cancer

    NASA Astrophysics Data System (ADS)

    Allsopp, Philip; Rowland, Ian

    Colorectal cancer (CRC) is the fourth most frequent cause of cancer related mortality in the world. Approximately 944,000 new cases were diagnosed globally in 2000 and this accounts for 9.2% of all new cancer cases (IARC, 2000). In Western societies namely Europe, North America and Australasia, it is the second most prevalent cancer after lung/breast (Boyle and Langman, 2000). About 363,000 new cases were reported in Europe in 2000 and it affects 6% of men and women by age 75, in almost equal proportion.

  20. Recent advances in active specific cancer vaccine treatment for colorectal cancer.

    PubMed

    Okuno, Kiyotaka; Sugiura, Fumiaki; Itoh, Kyogo; Yoshida, Koji; Tsunoda, Takuya; Nakamura, Yusuke

    2012-06-01

    Cloning techniques to identify genes and peptides of tumor-associated antigens have created new possibilities for the immunotherapy of patients with advanced cancer. Here, we review recent clinical trials of specific cancer vaccines, mainly HLA-restricted peptides, and epitope-encoding vectors for advanced colorectal cancer (CRC). Many researchers initially focused on carcinoembryonic antigen (CEA) as an immunologic target antigen that is overexpressed on virtually all CRCs. A recombinant vaccine containing the CEA gene and dendritic cells (DCs) loaded with CEA peptide was administered to patients with CEA-elevated CRC. Although CEA-specific responses were detected, the clinical responses were limited. Recently, new types of clinical trials--namely, a personalized protocol to take into account the immunological diversity of cytotoxic T cell responses among patients and a novel cancer-testis antigen protocol that uses multiple peptides derived from genes identified by the cDNA array method--have been introduced. The personalized protocol seemed to be better than the classical (non-personalized) protocol in terms of clinical response and survival. Novel cancer-testis antigen protocols that use multiple CRC-derived peptides were recently conducted in patients with advanced CRC. The preliminary study yielded promising results regarding specific T cell responses to peptides and survival benefits. In this review, we summarize these results and discuss future perspectives. PMID:22339221

  1. Oncogene Mutations in Colorectal Polyps Identified in the Norwegian Colorectal Cancer Prevention (NORCCAP) Screening Study

    PubMed Central

    Lorentzen, Jon A.; Grzyb, Krzysztof; De Angelis, Paula M.; Hoff, Geir; Eide, Tor J.; Andresen, Per Arne

    2016-01-01

    Data are limited on oncogene mutation frequencies in polyps from principally asymptomatic participants of population-based colorectal cancer screening studies. In this study, DNA from 204 polyps, 5 mm or larger, were collected from 176 participants of the NORCCAP screening study and analyzed for mutations in KRAS, BRAF, and PIK3CA including the rarely studied KRAS exons 3 and 4 mutations. KRAS mutations were identified in 23.0% of the lesions and were significantly associated with tubulovillous adenomas and large size. A significantly higher frequency of KRAS mutations in females was associated with mutations in codon 12. The KRAS exon 3 and 4 mutations constituted 23.4% of the KRAS positive lesions, which is a larger proportion compared to previous observations in colorectal cancer. BRAF mutations were identified in 11.3% and were associated with serrated polyps. None of the individuals were diagnosed with de novo or recurrent colorectal cancer during the follow-up time (median 11.2 years). Revealing differences in mutation-spectra according to gender and stages in tumorigenesis might be important for optimal use of oncogenes as therapeutic targets and biomarkers. PMID:27656095

  2. Oncogene Mutations in Colorectal Polyps Identified in the Norwegian Colorectal Cancer Prevention (NORCCAP) Screening Study.

    PubMed

    Lorentzen, Jon A; Grzyb, Krzysztof; De Angelis, Paula M; Hoff, Geir; Eide, Tor J; Andresen, Per Arne

    2016-01-01

    Data are limited on oncogene mutation frequencies in polyps from principally asymptomatic participants of population-based colorectal cancer screening studies. In this study, DNA from 204 polyps, 5 mm or larger, were collected from 176 participants of the NORCCAP screening study and analyzed for mutations in KRAS, BRAF, and PIK3CA including the rarely studied KRAS exons 3 and 4 mutations. KRAS mutations were identified in 23.0% of the lesions and were significantly associated with tubulovillous adenomas and large size. A significantly higher frequency of KRAS mutations in females was associated with mutations in codon 12. The KRAS exon 3 and 4 mutations constituted 23.4% of the KRAS positive lesions, which is a larger proportion compared to previous observations in colorectal cancer. BRAF mutations were identified in 11.3% and were associated with serrated polyps. None of the individuals were diagnosed with de novo or recurrent colorectal cancer during the follow-up time (median 11.2 years). Revealing differences in mutation-spectra according to gender and stages in tumorigenesis might be important for optimal use of oncogenes as therapeutic targets and biomarkers. PMID:27656095

  3. Oncogene Mutations in Colorectal Polyps Identified in the Norwegian Colorectal Cancer Prevention (NORCCAP) Screening Study

    PubMed Central

    Lorentzen, Jon A.; Grzyb, Krzysztof; De Angelis, Paula M.; Hoff, Geir; Eide, Tor J.; Andresen, Per Arne

    2016-01-01

    Data are limited on oncogene mutation frequencies in polyps from principally asymptomatic participants of population-based colorectal cancer screening studies. In this study, DNA from 204 polyps, 5 mm or larger, were collected from 176 participants of the NORCCAP screening study and analyzed for mutations in KRAS, BRAF, and PIK3CA including the rarely studied KRAS exons 3 and 4 mutations. KRAS mutations were identified in 23.0% of the lesions and were significantly associated with tubulovillous adenomas and large size. A significantly higher frequency of KRAS mutations in females was associated with mutations in codon 12. The KRAS exon 3 and 4 mutations constituted 23.4% of the KRAS positive lesions, which is a larger proportion compared to previous observations in colorectal cancer. BRAF mutations were identified in 11.3% and were associated with serrated polyps. None of the individuals were diagnosed with de novo or recurrent colorectal cancer during the follow-up time (median 11.2 years). Revealing differences in mutation-spectra according to gender and stages in tumorigenesis might be important for optimal use of oncogenes as therapeutic targets and biomarkers.

  4. Six-Year Experience of a Nurse-Led Colorectal Cancer Follow-Up Clinic

    PubMed Central

    Al Chalabi, Hasan; O'Riordan, James M.; Richardson, Alex; Flannery, Delia; O'Connor, Katrina; Stuart, Charlotte; Larkin, John; McCormick, Paul; Mehigan, Brian

    2014-01-01

    Aims and Objectives. To review the experience of a nurse-led colorectal cancer follow-up clinic in a tertiary referral colorectal cancer centre. Methodology. Data from the nurse-led colorectal cancer follow-up clinic in our unit was prospectively maintained in a colorectal cancer database. Data was analysed from January 1, 2006 until the December 31, 2011. Results. 1125 patients were diagnosed with colorectal cancer, and referred to our unit as a tertiary centre for specialised colorectal cancer. Nine hundred and four patients had surgical resection of their colorectal cancer. Four hundred and seven patients were referred to the nurse-led colorectal cancer clinic for surveillance. The mean age of the patient cohort was 67 years (range 32–88) and 56% of patients were male. One hundred and seventeen patients were discharged to their general practitioner having been disease free after 5 years of followup. Fifty-four patients were diagnosed with either local or distant recurrence. Conclusion. A nurse-led colorectal cancer follow-up clinic is running according to strict follow-up protocols. This type of clinic significantly reduces the number of routine follow-up patients that have to be seen by the colorectal surgical consultant. PMID:25374950

  5. New Molecular Features of Colorectal Cancer Identified - Office of Cancer Clinical Proteomics Research

    Cancer.gov

    Investigators from the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) who comprehensively analyzed 95 human colorectal tumor samples, have determined how gene alterations identified in previous analyses of the same samples

  6. The genomic landscapes of human breast and colorectal cancers.

    PubMed

    Wood, Laura D; Parsons, D Williams; Jones, Siân; Lin, Jimmy; Sjöblom, Tobias; Leary, Rebecca J; Shen, Dong; Boca, Simina M; Barber, Thomas; Ptak, Janine; Silliman, Natalie; Szabo, Steve; Dezso, Zoltan; Ustyanksky, Vadim; Nikolskaya, Tatiana; Nikolsky, Yuri; Karchin, Rachel; Wilson, Paul A; Kaminker, Joshua S; Zhang, Zemin; Croshaw, Randal; Willis, Joseph; Dawson, Dawn; Shipitsin, Michail; Willson, James K V; Sukumar, Saraswati; Polyak, Kornelia; Park, Ben Ho; Pethiyagoda, Charit L; Pant, P V Krishna; Ballinger, Dennis G; Sparks, Andrew B; Hartigan, James; Smith, Douglas R; Suh, Erick; Papadopoulos, Nickolas; Buckhaults, Phillip; Markowitz, Sanford D; Parmigiani, Giovanni; Kinzler, Kenneth W; Velculescu, Victor E; Vogelstein, Bert

    2007-11-16

    Human cancer is caused by the accumulation of mutations in oncogenes and tumor suppressor genes. To catalog the genetic changes that occur during tumorigenesis, we isolated DNA from 11 breast and 11 colorectal tumors and determined the sequences of the genes in the Reference Sequence database in these samples. Based on analysis of exons representing 20,857 transcripts from 18,191 genes, we conclude that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene "mountains" and a much larger number of gene "hills" that are mutated at low frequency. We describe statistical and bioinformatic tools that may help identify mutations with a role in tumorigenesis. These results have implications for understanding the nature and heterogeneity of human cancers and for using personal genomics for tumor diagnosis and therapy.

  7. The Multidisciplinary Management of Colorectal Cancer: Present and Future Paradigms.

    PubMed

    Sievers, Chelsie K; Kratz, Jeremy D; Zurbriggen, Luke D; LoConte, Noelle K; Lubner, Sam J; Uboha, Natalya; Mulkerin, Daniel; Matkowskyj, Kristina A; Deming, Dustin A

    2016-09-01

    As treatment strategies for patients with colorectal cancer advance, there has now become an ever-increasing need for multidisciplinary teams to care for these patients. Recent investigations into the timing and duration of perioperative therapy, as well as, the rise of molecular profiling have led to more systemic chemotherapeutic options. The most efficacious use, in terms of timing and patient selection, of these therapies in the setting of modern operative and radiotherapy techniques requires the generation of care teams discussing cases at multidisciplinary conferences. This review highlights the role of multidisciplinary team conferences, advances in perioperative chemotherapy, current clinical biomarkers, and emerging therapeutic agents for molecular subtypes of metastatic colon cancer. As our understanding of relevant molecular subtypes increases and as data becomes available on treatment response, the treatment of colorectal cancer will become more precise and effective. PMID:27582648

  8. Estimation of National Colorectal-Cancer Incidence Using Claims Databases

    PubMed Central

    Quantin, C.; Benzenine, E.; Hägi, M.; Auverlot, B.; Abrahamowicz, M.; Cottenet, J.; Fournier, E.; Binquet, C.; Compain, D.; Monnet, E.; Bouvier, A. M.; Danzon, A.

    2012-01-01

    Background. The aim of the study was to assess the accuracy of the colorectal-cancer incidence estimated from administrative data. Methods. We selected potential incident colorectal-cancer cases in 2004-2005 French administrative data, using two alternative algorithms. The first was based only on diagnostic and procedure codes, whereas the second considered the past history of the patient. Results of both methods were assessed against two corresponding local cancer registries, acting as “gold standards.” We then constructed a multivariable regression model to estimate the corrected total number of incident colorectal-cancer cases from the whole national administrative database. Results. The first algorithm provided an estimated local incidence very close to that given by the regional registries (646 versus 645 incident cases) and had good sensitivity and positive predictive values (about 75% for both). The second algorithm overestimated the incidence by about 50% and had a poor positive predictive value of about 60%. The estimation of national incidence obtained by the first algorithm differed from that observed in 14 registries by only 2.34%. Conclusion. This study shows the usefulness of administrative databases for countries with no national cancer registry and suggests a method for correcting the estimates provided by these data. PMID:22792103

  9. Advances and perspectives of colorectal cancer stem cell vaccine.

    PubMed

    Guo, Mei; Dou, Jun

    2015-12-01

    Colorectal cancer is essentially an environmental and genetic disease featured by uncontrolled cell growth and the capability to invade other parts of the body by forming metastases, which inconvertibly cause great damage to tissues and organs. It has become one of the leading causes of cancer-related mortality in the developed countries such as United States, and approximately 1.2 million new cases are yearly diagnosed worldwide, with the death rate of more than 600,000 annually and incidence rates are increasing in most developing countries. Apart from the generally accepted theory that pathogenesis of colorectal cancer consists of genetic mutation of a certain target cell and diversifications in tumor microenvironment, the colorectal cancer stem cells (CCSCs) theory makes a different explanation, stating that among millions of colon cancer cells there is a specific and scanty cellular population which possess the capability of self-renewal, differentiation and strong oncogenicity, and is tightly responsible for drug resistance and tumor metastasis. Based on these characteristics, CCSCs are becoming a novel target cells both in the clinical and the basic studies, especially the study of CCSCs vaccines due to induced efficient immune response against CCSCs. This review provides an overview of CCSCs and preparation technics and targeting factors related to CCSCs vaccines in detail.

  10. RHOA inactivation enhances Wnt signaling and promotes colorectal cancer

    PubMed Central

    Rodrigues, Paulo; Macaya, Irati; Bazzocco, Sarah; Mazzolini, Rocco; Andretta, Elena; Dopeso, Higinio; Mateo-Lozano, Silvia; Bilić, Josipa; Cartón-García, Fernando; Nieto, Rocio; Suárez-López, Lucia; Afonso, Elsa; Landolfi, Stefania; Hernandez-Losa, Javier; Kobayashi, Kazuto; Cajal, Santiago Ramón y; Tabernero, Josep; Tebbutt, Niall C.; Mariadason, John M.; Schwartz, Simo; Arango, Diego

    2014-01-01

    Activation of the small GTPase RHOA has strong oncogenic effects in many tumor types, although its role in colorectal cancer remains unclear. Here we show that RHOA inactivation contributes to colorectal cancer progression/metastasis, largely through the activation of Wnt/β-catenin signaling. RhoA inactivation in the murine intestine accelerates the tumorigenic process and in human colon cancer cells leads to the redistribution of β-catenin from the membrane to the nucleus and enhanced Wnt/β-catenin signaling, resulting in increased proliferation, invasion and de-differentiation. In mice, RHOA inactivation contributes to colon cancer metastasis and reduced RHOA levels were observed at metastatic sites compared to primary human colon tumors. Therefore, we have identified a new mechanism of activation of Wnt/β-catenin signaling and characterized the role of RHOA as a novel tumor suppressor in colorectal cancer. These results constitute a shift from the current paradigm and demonstrate that RHO GTPases can suppress tumor progression and metastasis. PMID:25413277

  11. Colorectal cancer chemoprevention by trans-resveratrol.

    PubMed

    Juan, M Emília; Alfaras, Irene; Planas, Joana M

    2012-06-01

    trans-Resveratrol (trans-3,4',5-trihydroxystilbene) is a natural phytoalexin present in grapes, red wine, berries and peanuts with health protecting properties. The low oral bioavailability indicated for this polyphenol, with the intestine as a bottleneck to its absorption, has promoted the large intestine as a potential target site for its chemopreventive activity. This review recapitulates the current evidence of the effects of trans-resveratrol on colon cancer. First, we describe the studies conducted in vitro which show that the protective activity takes place by inhibition of proliferation and induction of apoptosis. Secondly, the chemopreventive activity in animal models of colon carcinogenesis is revised. trans-Resveratrol not only reduces the number of preneoplastic lesions but also the incidence and multiplicity of tumors. Lastly, the article also reviews the available data on clinical trials. Altogether, the present findings support the hypothesis that the oral administration of trans-resveratrol might contribute to the prevention of colon carcinogenesis.

  12. Intraoperative and external beam irradiation for locally advanced colorectal cancer.

    PubMed Central

    Gunderson, L L; Martin, J K; Bèart, R W; Nagorney, D M; Fieck, J M; Wieand, H S; Martinez, A; O'Connell, M J; Martenson, J A; McIlrath, D C

    1988-01-01

    In view of poor local control rates obtained with standard treatment, intraoperative radiation (IORT) using electrons was combined with external beam irradiation and surgical resection, with or without 5-fluorouracil (5FU), in 51 patients with locally advanced colorectal cancer (recurrent, 36 patients; primary, 15 patients). Patients received 4500-5500 cGy (rad) of fractionated, multiple field external beam irradiation and an IORT dose of 1000-2000 cGy. Thirty of 51 patients (59%) are alive and 22 patients (43%) are free of disease. In 44 patients at risk greater than or equal to 1 year, local progression within the IORT field has occurred in 1 of 44 (2%) and within the external beam field in 8 of 44 (18%). All local failures have occurred in patients with recurrence or with gross residual after partial resection, and the risk was less in patients who received 5FU during external irradiation (1 of 11, 9% vs. 6 of 31, 19%). The incidence of distant metastases is high in patients with recurrence, but subsequent peritoneal failures are infrequent. Acute and chronic tolerance have been acceptable, but peripheral nerve appears to be a dose-limiting structure. Randomized trials are needed to determine whether potential gains with IORT are real. PMID:3337561

  13. Primary and secondary prevention of colorectal cancer in the Czech Republic.

    PubMed

    Azeem, Kateřina; Ševčíková, Jarmila; Kyselý, Zdeněk; Horáková, Dagmar; Vlčková, Jana; Kollárová, Helena

    2016-01-01

    Colorectal cancer is one of the most frequent malignancies in the Czech Republic and worldwide. Also, a high prevalence of overweight and obesity, a high proportion of smokers in the population, and one of the highest per capita alcohol consumption rates are typical for the Czech population. The role of general practitioners in the prevention of colorectal cancer is crucial. In primary prevention, the doctor should emphasise the importance of a healthy lifestyle - a balanced diet rich in fruits and vegetables, maintaining a normal body weight, adequate physical activity, and non-smoking. In secondary prevention, patients should be informed about the possibilities of colorectal cancer screening and the benefits of early detection of the disease. Participation rates of the target population for colorectal cancer screening are low. Steps leading to increased participation in colorectal cancer screening (including postal invitations) play an important role in influencing the mortality of colorectal cancer.

  14. Primary and secondary prevention of colorectal cancer in the Czech Republic

    PubMed Central

    Azeem, Kateřina; Ševčíková, Jarmila; Kyselý, Zdeněk; Horáková, Dagmar; Vlčková, Jana

    2016-01-01

    Colorectal cancer is one of the most frequent malignancies in the Czech Republic and worldwide. Also, a high prevalence of overweight and obesity, a high proportion of smokers in the population, and one of the highest per capita alcohol consumption rates are typical for the Czech population. The role of general practitioners in the prevention of colorectal cancer is crucial. In primary prevention, the doctor should emphasise the importance of a healthy lifestyle – a balanced diet rich in fruits and vegetables, maintaining a normal body weight, adequate physical activity, and non-smoking. In secondary prevention, patients should be informed about the possibilities of colorectal cancer screening and the benefits of early detection of the disease. Participation rates of the target population for colorectal cancer screening are low. Steps leading to increased participation in colorectal cancer screening (including postal invitations) play an important role in influencing the mortality of colorectal cancer. PMID:27110303

  15. Early tumor cavitation with regorafenib in metastatic colorectal cancer: A case report

    PubMed Central

    KAWASAKI, KENTA; HAMAMOTO, YASUO; ADACHI, MASAYUKI; KANAI, TAKANORI; TAKAISHI, HIROMASA

    2016-01-01

    Tumoral cavity formation is a characteristic phenomenon reported in anti-angiogenic therapy in lung lesions. A 57-year-old male with multiple pulmonary metastases from colorectal cancer treated with an oral tyrosine kinase inhibitor, regorafenib, exhibited a characteristic cavity formation after the first two cycles. The decrease in the size of tumors was calculated as 38%, and there were associated decreases in the serum concentrations of the tumor markers carcinoembryonic antigen and CA19-9. After eight cycles of treatment, the cavity gradually disappeared through filling-in. This unique morphological response is not only reported in lung cancer but also in liver metastasis in colorectal cancer. However, the association between morphological changes including cavity formation and clinical benefit remains controversial. Pulmonary hemorrhage and pneumothorax are well-known consequences of cavitation, as reported with the other anti-angiogenic inhibitors. Early tumor cavitation in lung metastasis may demonstrate the predictive potential of regorafenib in colorectal cancer, although it is necessary to be mindful of toxicity. PMID:26870193

  16. PKLR promotes colorectal cancer liver colonization through induction of glutathione synthesis

    PubMed Central

    Nguyen, Alexander; Loo, Jia Min; Mital, Rohit; Weinberg, Ethan M.; Man, Fung Ying; Zeng, Zhaoshi; Paty, Philip B.; Saltz, Leonard; Janjigian, Yelena Y.; de Stanchina, Elisa; Tavazoie, Sohail F.

    2016-01-01

    Colorectal cancer metastasis to the liver is a major cause of cancer-related death; however, the genes and pathways that govern this metastatic colonization event remain poorly characterized. Here, using a large-scale in vivo RNAi screen, we identified liver and red blood cell pyruvate kinase (PKLR) as a driver of metastatic liver colonization. PKLR expression was increased in liver metastases as well as in primary colorectal tumors of patients with metastatic disease. Evaluation of a murine liver colonization model revealed that PKLR promotes cell survival in the tumor core during conditions of high cell density and oxygen deprivation by increasing glutathione, the primary endogenous antioxidant. PKLR negatively regulated the glycolytic activity of PKM2, the major pyruvate kinase isoenzyme known to regulate cellular glutathione levels. Glutathione is critical for metastasis, and we determined that the rate-limiting enzyme of glutathione synthesis, GCLC, becomes overexpressed in patient liver metastases, promotes cell survival under hypoxic and cell-dense conditions, and mediates metastatic liver colonization. RNAi-mediated inhibition of glutathione synthesis impaired survival of multiple colon cancer cell lines, and pharmacological targeting of this metabolic pathway reduced colonization in a primary patient-derived xenograft model. Our findings highlight the impact of metabolic reprogramming within the niche as metastases progress and suggest clinical potential for targeting this pathway in colorectal cancer. PMID:26784545

  17. CCR5 blockage by maraviroc induces cytotoxic and apoptotic effects in colorectal cancer cells.

    PubMed

    Pervaiz, Asim; Ansari, Shariq; Berger, Martin R; Adwan, Hassan

    2015-05-01

    Alterations in the expression of C-C chemokine receptor type 5 (CCR5 or CD195) have been correlated with disease progression in different cancers. Recently, a few investigations have reported the blockage of this receptor by an antagonist (maraviroc) and its antineoplastic effects on tumor cell growth. However, little is known about the mechanistic reasons behind these antineoplastic effects of CCR5 blockage by maraviroc. In this study, we blocked the CCR5 receptor by maraviroc in SW480 and SW620 colorectal cancer cells to study the resulting changes in biological properties and related pathways. This blockage induced significantly reduced proliferation and a profound arrest in G1 phase of the cell cycle. Concomitantly, maraviroc caused significant signs of apoptosis at morphological level. Significant modulation of multiple apoptosis-relevant genes was also noticed at mRNA levels. In addition, we found remarkable increases in cleaved caspases at protein level. These modulations led us to propose a signaling pathway for the observed apoptotic effects. In conclusion, blocking the CCR5 by maraviroc induces significant cytotoxic and apoptotic effects in colorectal cancer cells. Thus, maraviroc can be considered a model compound, which may foster the development of further CCR5 antagonists to be used for the treatment of colorectal cancer.

  18. Knowledge of colorectal cancer screening among young Malaysians.

    PubMed

    Al-Naggar, Redhwan Ahmed; Bobryshev, Yuri V

    2013-01-01

    The objective of this study was to determine the knowledge and associated factors regarding colorectal cancer screening among university students in Malaysia. The questionnaire consisted of three parts: socio-demographic characteristics, lifestyle practice and knowledge of colorectal screening. A cross-sectional study was conducted among 300 students (21.3±1.4 years old). The majority of the participants were Malay with a monthly family income of less than 5,000 Ringgit Malaysia (equal to 1,700 USD) (67.0% and 76.0%, respectively). Regarding their lifestyle practices, the majority were non-smokers and had never consumed alcohol (83.7%, and 88.0%, respectively). The majority of the participants had no knowledge of digital rectal examination, colonoscopy, barium enema and fecal occult blood screening (63.3%, 60.7%, 74.0% and 62.3%, respectively). Univariate and multivariate analysis revealed that their age and the discipline which the students were studying significantly influenced their level of knowledge about colorectal screening. The present study results indicate that education campaigns about colorectal cancer should be promoted. PMID:23679301

  19. Clues to the pathogenesis of familial colorectal cancer

    SciTech Connect

    Aaltonen, L.A.; Peltomaeki, P.; Pylkkaenen, L.; Chappelle, A. de la ); Leach, F.S.; Powell, S.M.; Jen, J.; Hamilton, S.R.; Petersen, G.M.; Kinzler, K.W.; Vogelstein, B. Johns Hopkins Hospital, Baltimore, MD ); Sistonen, P. Finnish Red Cross Blood Transfusion Service, Helsinki ); Mecklin, J.P. ); Jaervinen, H. )

    1993-05-07

    A predisposition to colorectal cancer is shown to be linked to markers on chromosome 2 in some families. Molecular features of familial cancers were compared with those of sporadic colon cancers. Neither the familial nor sporadic cancers showed loss of heterozygosity for chromosome 2 markers, and the incidence of mutations in KRAS, P53, and APC was similar in the two groups of tumors. Most of the familial cancers, however, had widespread alterations in short repeated DNA sequences, suggesting that numerous replication errors had occurred during tumor development. Thirteen percent of sporadic cancers had identical abnormalities and these cancers shared biologic properties with the familial cases. These data suggest a mechanism for familial tumorigenesis different from that mediated by classic tumor suppressor genes. 22 refs., 2 figs., 2 tabs.

  20. Risk of Advanced Neoplasia in First-Degree Relatives with Colorectal Cancer: A Large Multicenter Cross-Sectional Study

    PubMed Central

    Quintero, Enrique; Gargallo, Carla; Lanas, Angel; Bujanda, Luis; Gimeno-García, Antonio Z.; Hernández-Guerra, Manuel; Nicolás-Pérez, David; Alonso-Abreu, Inmaculada; Morillas, Juan Diego; Balaguer, Francesc; Muriel, Alfonso

    2016-01-01

    Background First-degree relatives (FDR) of patients with colorectal cancer have a higher risk of developing colorectal cancer than the general population. For this reason, screening guidelines recommend colonoscopy every 5 or 10 y, starting at the age of 40, depending on whether colorectal cancer in the index-case is diagnosed at <60 or ≥60 y, respectively. However, studies on the risk of neoplastic lesions are inconclusive. The aim of this study was to determine the risk of advanced neoplasia (three or more non-advanced adenomas, advanced adenoma, or invasive cancer) in FDR of patients with colorectal cancer compared to average-risk individuals (i.e., asymptomatic adults 50 to 69 y of age with no family history of colorectal cancer). Methods and Findings This cross-sectional analysis includes data from 8,498 individuals undergoing their first lifetime screening colonoscopy between 2006 and 2012 at six Spanish tertiary hospitals. Of these individuals, 3,015 were defined as asymptomatic FDR of patients with colorectal cancer (“familial-risk group”) and 3,038 as asymptomatic with average-risk for colorectal cancer (“average-risk group”). The familial-risk group was stratified as one FDR, with one family member diagnosed with colorectal cancer at ≥60 y (n = 1,884) or at <60 y (n = 831), and as two FDR, with two family members diagnosed with colorectal cancer at any age (n = 300). Multiple logistic regression analysis was used for between-group comparisons after adjusting for potential confounders (age, gender, and center). Compared with the average-risk group, advanced neoplasia was significantly more prevalent in individuals having two FDR with colorectal cancer (odds ratio [OR] 1.90; 95% confidence interval [CI] 1.36–2.66, p < 0.001), but not in those having one FDR with colorectal cancer diagnosed at ≥60 y (OR 1.03; 95% CI 0.83–1.27, p = 0.77) and <60 y (OR 1.19; 95% CI 0.90–1.58, p = 0.20). After the age of 50 y, men developed advanced

  1. Colorectal cancer mortality and incidence in Campbell County, Kentucky

    SciTech Connect

    Richmond, R.E.; Rickabaugh, J.; Huffman, J.; Epperly, N.

    1987-08-01

    Previous publications have reported an unusually high colon cancer mortality rate for several Kentucky counties. We investigated these high rates by examining incidence of colorectal cancer in one county with a high mortality. The objective was to determine whether the incidence of colorectal cancer was as high as mortality rates indicated and, if so, to look for possible etiologic factors for the high rates. We found the incidence of colon cancer to be significantly higher in Campbell County than expected. While we expected 162 cases of colon cancer, we actually observed 192 (P less than .01). The number of rectal cancers was no higher than expected (52 expected and 62 observed), in agreement with previously reported mortality figures. A geographic plot of cases by home residence showed a significantly higher rate of colon cancer for urban county regions than for rural regions. In fact, the population of rural Campbell County had a colon cancer rate significantly lower than either the county rate or the national rate. Several factors were analyzed to explain these rate differences. The only consistently associated factor was source of residential drinking water.

  2. HER2 activating mutations are targets for colorectal cancer treatment

    PubMed Central

    Kavuri, Shyam M.; Jain, Naveen; Galimi, Francesco; Cottino, Francesca; Leto, Simonetta M.; Migliardi, Giorgia; Searleman, Adam C.; Shen, Wei; Monsey, John; Trusolino, Livio; Jacobs, Samuel A.; Bertotti, Andrea; Bose, Ron

    2015-01-01

    The Cancer Genome Atlas project identified HER2 somatic mutations and gene amplification in 7% of colorectal cancer patients. Introduction of the HER2 mutations, S310F, L755S, V777L, V842I, and L866M, into colon epithelial cells increased signaling pathways and anchorage-independent cell growth, indicating that they are activating mutations. Introduction of these HER2 activating mutations into colorectal cancer cell lines produced resistance to cetuximab and panitumumab by sustaining MAPK phosphorylation. HER2 mutations are potently inhibited by low nanomolar doses of the irreversible tyrosine kinase inhibitors, neratinib and afatinib. HER2 gene sequencing of 48 cetuximab resistant, quadruple (KRAS, NRAS, BRAF, and PIK3CA) WT colorectal cancer patient-derived xenografts (PDX’s) identified 4 PDX’s with HER2 mutations. HER2 targeted therapies were tested on two PDX’s. Treatment with a single HER2 targeted drug (trastuzumab, neratinib, or lapatinib) delayed tumor growth, but dual HER2 targeted therapy with trastuzumab plus tyrosine kinase inhibitors produced regression of these HER2 mutated PDX’s. PMID:26243863

  3. Clinical Perspectives on Colorectal Cancer Screening at Latino-Serving Federally Qualified Health Centers

    ERIC Educational Resources Information Center

    Coronado, Gloria D.; Petrik, Amanda F.; Spofford, Mark; Talbot, Jocelyn; Do, Huyen Hoai; Taylor, Victoria M.

    2015-01-01

    Purpose: Colorectal cancer is the second most common cause of cancer death in the United States, and rates of screening for colorectal cancer are low. We sought to gather the perceptions of clinic personnel at Latino-serving Federally Qualified Health Centers (operating 17 clinics) about barriers to utilization of screening services for colorectal…

  4. Meat intake, cooking methods, dietary carcinogens, and colorectal cancer risk: findings from the Colorectal Cancer Family Registry.

    PubMed

    Joshi, Amit D; Kim, Andre; Lewinger, Juan Pablo; Ulrich, Cornelia M; Potter, John D; Cotterchio, Michelle; Le Marchand, Loic; Stern, Mariana C

    2015-06-01

    Diets high in red meat and processed meats are established colorectal cancer (CRC) risk factors. However, it is still not well understood what explains this association. We conducted comprehensive analyses of CRC risk and red meat and poultry intakes, taking into account cooking methods, level of doneness, estimated intakes of heterocyclic amines (HCAs) that accumulate during meat cooking, tumor location, and tumor mismatch repair proficiency (MMR) status. We analyzed food frequency and portion size data including a meat cooking module for 3364 CRC cases, 1806 unaffected siblings, 136 unaffected spouses, and 1620 unaffected population-based controls, recruited into the CRC Family Registry. Odds ratios (OR) and 95% confidence intervals (CI) for nutrient density variables were estimated using generalized estimating equations. We found no evidence of an association between total nonprocessed red meat or total processed meat and CRC risk. Our main finding was a positive association with CRC for pan-fried beefsteak (P(trend) < 0.001), which was stronger among MMR deficient cases (heterogeneity P = 0.059). Other worth noting associations, of borderline statistical significance after multiple testing correction, were a positive association between diets high in oven-broiled short ribs or spareribs and CRC risk (P(trend) = 0.002), which was also stronger among MMR-deficient cases, and an inverse association with grilled hamburgers (P(trend) = 0.002). Our results support the role of specific meat types and cooking practices as possible sources of human carcinogens relevant for CRC risk.

  5. Distribution of Ca, Fe, Cu and Zn in primary colorectal cancer and secondary colorectal liver metastases

    NASA Astrophysics Data System (ADS)

    Al-Ebraheem, A.; Mersov, A.; Gurusamy, K.; Farquharson, M. J.

    2010-07-01

    A microbeam synchrotron X-ray fluorescence (μSRXRF) technique has been used to determine the localization and the relative concentrations of Zn, Cu, Fe and Ca in primary colorectal cancer and secondary colorectal liver metastases. 24 colon and 23 liver samples were examined, all of which were formalin fixed tissues arranged as microarrays of 1.0 mm diameter and 10 μm thickness. The distribution of these metals was compared with light transmission images of adjacent sections that were H and E stained to reveal the location of the cancer cells. Histological details were provided for each sample which enable concentrations of all elements in different tissue types to be compared. In the case of liver, significant differences have been found for all elements when comparing tumour, normal, necrotic, fibrotic, and blood vessel tissues (Kruskal Wallis Test, P<0.0001). The concentrations of all elements have also been found to be significantly different among tumour, necrotic, fibrotic, and mucin tissues in the colon samples (Kruskal Wallis Test, P<0.0001). The concentrations of all elements have been compared between primary colorectal samples and colorectal liver metastases. Concentration of Zn, Cu, Fe and Ca are higher in all types of liver tissues compared to those in the colon tissues. Comparing liver tumour and colon tumour samples, significant differences have been found for all elements (Mann Whitney, P<0.0001). For necrotic tissues, significant increase has been found for Zn, Ca, Cu and Fe (Mann Whitney, P<0.0001 for Fe and Zn, 0.014 for Ca, and 0.001 for Cu). The liver fibrotic levels of Zn, Ca, Cu and Fe were higher than the fibrotic colon areas (independent T test, P=0.007 for Zn and Mann Whitney test P<0.0001 for Cu, Fe and Ca). For the blood vessel tissue, the analysis revealed that the difference was only significant for Fe ( P=0.009) from independent T test.

  6. Evaluation of FTIR spectroscopy as diagnostic tool for colorectal cancer using spectral analysis

    NASA Astrophysics Data System (ADS)

    Dong, Liu; Sun, Xuejun; Chao, Zhang; Zhang, Shiyun; Zheng, Jianbao; Gurung, Rajendra; Du, Junkai; Shi, Jingsen; Xu, Yizhuang; Zhang, Yuanfu; Wu, Jinguang

    2014-03-01

    The aim of this study is to confirm FTIR spectroscopy as a diagnostic tool for colorectal cancer. 180 freshly removed colorectal samples were collected from 90 patients for spectrum analysis. The ratios of spectral intensity and relative intensity (/I1460) were calculated. Principal component analysis (PCA) and Fisher's discriminant analysis (FDA) were applied to distinguish the malignant from normal. The FTIR parameters of colorectal cancer and normal tissues were distinguished due to the contents or configurations of nucleic acids, proteins, lipids and carbohydrates. Related to nitrogen containing, water, protein and nucleic acid were increased significantly in the malignant group. Six parameters were selected as independent factors to perform discriminant functions. The sensitivity for FTIR in diagnosing colorectal cancer was 96.6% by discriminant analysis. Our study demonstrates that FTIR can be a useful technique for detection of colorectal cancer and may be applied in clinical colorectal cancer diagnosis.

  7. T-oligo as an anticancer agent in colorectal cancer

    SciTech Connect

    Wojdyla, Luke; Stone, Amanda L.; Sethakorn, Nan; Uppada, Srijayaprakash B.; Devito, Joseph T.; Bissonnette, Marc; Puri, Neelu

    2014-04-04

    Highlights: • T-oligo induces cell cycle arrest, senescence, apoptosis, and differentiation in CRC. • Treatment with T-oligo downregulates telomere-associated proteins. • T-oligo combined with an EGFR-TKI additively inhibits cellular proliferation. • T-oligo has potential as an effective therapeutic agent for CRC. - Abstract: In the United States, there will be an estimated 96,830 new cases of colorectal cancer (CRC) and 50,310 deaths in 2014. CRC is often detected at late stages of the disease, at which point there is no effective chemotherapy. Thus, there is an urgent need for effective novel therapies that have minimal effects on normal cells. T-oligo, an oligonucleotide homologous to the 3′-telomere overhang, induces potent DNA damage responses in multiple malignant cell types, however, its efficacy in CRC has not been studied. This is the first investigation demonstrating T-oligo-induced anticancer effects in two CRC cell lines, HT-29 and LoVo, which are highly resistant to conventional chemotherapies. In this investigation, we show that T-oligo may mediate its DNA damage responses through the p53/p73 pathway, thereby inhibiting cellular proliferation and inducing apoptosis or senescence. Additionally, upregulation of downstream DNA damage response proteins, including E2F1, p53 or p73, was observed. In LoVo cells, T-oligo induced senescence, decreased clonogenicity, and increased expression of senescence associated proteins p21, p27, and p53. In addition, downregulation of POT1 and TRF2, two components of the shelterin protein complex which protects telomeric ends, was observed. Moreover, we studied the antiproliferative effects of T-oligo in combination with an EGFR tyrosine kinase inhibitor, Gefitinib, which resulted in an additive inhibitory effect on cellular proliferation. Collectively, these data provide evidence that T-oligo alone, or in combination with other molecularly targeted therapies, has potential as an anti-cancer agent in CRC.

  8. Colorectal cancer screening tests: pros and cons, and for whom?

    PubMed

    Forbes, Geoffrey M

    2008-04-01

    The past decade has seen major advances internationally in the implementation of colorectal cancer screening, influenced in differing ways by the profession, the public and by government. Relatively unique to colorectal cancer screening is the availability of so many test alternatives, which have substantial variation in methodology. While perhaps spoilt for choice, discerning the key advantages and disadvantages of each test is often difficult, depending on the perspective from which screening is viewed. Accordingly, this article provides an evaluation of screening tests as might be perceived by governments, the patient and the profession. Aligned issues such as choosing a screening test and provision of informed consent are discussed. Finally, the article identifies current problems with various screening tests that, if attended to, might change the perception of a test's value to a particular interest group. PMID:19072355

  9. Fusobacterium nucleatum associates with stages of colorectal neoplasia development, colorectal cancer and disease outcome.

    PubMed

    Flanagan, L; Schmid, J; Ebert, M; Soucek, P; Kunicka, T; Liska, V; Bruha, J; Neary, P; Dezeeuw, N; Tommasino, M; Jenab, M; Prehn, J H M; Hughes, D J

    2014-08-01

    Commensal bacteria in the colon may play a role in colorectal cancer (CRC) development. Recent studies from North America showed that Fusobacterium nucleatum (Fn) infection is over-represented in disease tissue versus matched normal tissue in CRC patients. Using quantitative real-time polymerase chain reaction (qPCR) of DNA extracted from colorectal tissue biopsies and surgical resections of three European cohorts totalling 122 CRC patients, we found an over-abundance of Fn in cancerous compared to matched normal tissue (p < 0.0001). To determine whether Fn infection is an early event in CRC development, we assayed Fn in colorectal adenoma (CRA) tissue from 52 Irish patients. While for all CRAs the Fn level was not statistically significantly higher in disease versus normal tissue (p = 0.06), it was significantly higher for high-grade dysplasia (p = 0.015). As a secondary objective, we determined that CRC patients with low Fn levels had a significantly longer overall survival time than patients with moderate and high levels of the bacterium (p = 0.008). The investigation of Fn as a potential non-invasive biomarker for CRC screening showed that, while Fn was more abundant in stool samples from CRC patients compared to adenomas or controls, the levels in stool did not correlate with cancer or adenoma tissue levels from the same individuals. This is the first study examining Fn in the colonic tissue and stool of European CRC and CRA patients, and suggests Fn as a novel risk factor for disease progression from adenoma to cancer, possibly affecting patient survival outcomes. Our results highlight the potential of Fn detection as a diagnostic and prognostic determinant in CRC patients.

  10. Antiproliferative Activity of Triterpene Glycoside Nutrient from Monk Fruit in Colorectal Cancer and Throat Cancer

    PubMed Central

    Liu, Can; Dai, Longhai; Liu, Yueping; Rong, Long; Dou, Dequan; Sun, Yuanxia; Ma, Lanqing

    2016-01-01

    Colorectal cancer and throat cancer are the world’s most prevalent neoplastic diseases, and a serious threat to human health. Plant triterpene glycosides have demonstrated antitumor activity. In this study, we investigated potential anticancer effects of mogroside IVe, a triterpenoid glycoside from monk fruit, using in vitro and in vivo models of colorectal and laryngeal cancer. The effects of mogroside IVe on the proliferation of colorectal cancer HT29 cells and throat cancer Hep-2 cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the expression levels of p53, phosphorylated ERK1/2, and MMP-9 were analyzed by western blotting and immunohistochemistry. The results indicated that mogroside IVe inhibited, in a dose-dependent manner, the proliferation of HT29 and Hep-2 cells in culture and in xenografted mice, which was accompanied by the upregulation of tumor suppressor p53, and downregulation of matrix metallopeptidase 9 (MMP-9) and phosphorylated extracellular signal-regulated kinases (ERK)1/2. This study revealed the suppressive activity of mogroside IVe towards colorectal and throat cancers and identified the underlying mechanisms, suggesting that mogroside IVe may be potentially used as a biologically-active phytochemical supplement for treating colorectal and throat cancers. PMID:27304964

  11. Antiproliferative Activity of Triterpene Glycoside Nutrient from Monk Fruit in Colorectal Cancer and Throat Cancer.

    PubMed

    Liu, Can; Dai, Longhai; Liu, Yueping; Rong, Long; Dou, Dequan; Sun, Yuanxia; Ma, Lanqing

    2016-06-13

    Colorectal cancer and throat cancer are the world's most prevalent neoplastic diseases, and a serious threat to human health. Plant triterpene glycosides have demonstrated antitumor activity. In this study, we investigated potential anticancer effects of mogroside IVe, a triterpenoid glycoside from monk fruit, using in vitro and in vivo models of colorectal and laryngeal cancer. The effects of mogroside IVe on the proliferation of colorectal cancer HT29 cells and throat cancer Hep-2 cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the expression levels of p53, phosphorylated ERK1/2, and MMP-9 were analyzed by western blotting and immunohistochemistry. The results indicated that mogroside IVe inhibited, in a dose-dependent manner, the proliferation of HT29 and Hep-2 cells in culture and in xenografted mice, which was accompanied by the upregulation of tumor suppressor p53, and downregulation of matrix metallopeptidase 9 (MMP-9) and phosphorylated extracellular signal-regulated kinases (ERK)1/2. This study revealed the suppressive activity of mogroside IVe towards colorectal and throat cancers and identified the underlying mechanisms, suggesting that mogroside IVe may be potentially used as a biologically-active phytochemical supplement for treating colorectal and throat cancers.

  12. Collaborative colorectal cancer screening: a successful quality improvement initiative

    PubMed Central

    2003-01-01

    Problem: Low screening and referral rates for colorectal cancer at a primary care clinic suggest the need for alternative methods to identify patients and complete the screening process. Design: A review of >5000 medical charts established baseline screening and referral data. After a 3-month trial of a screening protocol, the research team conducted a follow-up medical chart review to determine referral levels. Background and setting: The clinic is an 8-physician primary care facility in Southlake, Texas, and is one of 36 clinics affiliated with HealthTexas Provider Network. Key measures for improvement: The goal was to increase referrals for colorectal cancer to at least 85% among patients aged 50 to 75 years. Strategies for improvement: The entire staff of the primary care clinic and the gastroenterology office became involved in the referral process. The team used simple tools such as chart stickers to draw attention to patients requiring screening, generation of referral forms that were numbered for follow-up and faxed to the gastroenterologists, and patient educational material on colorectal cancer screening. These tools were designed to overcome specific barriers to successful screening that the team had identified. Effects of change: Referrals for sigmoidoscopy, colonoscopy, and double- contrast barium enema increased from 47% to 86%. Fecal occult blood testing was arranged for additional patients through the primary care office. Revenues related to colonoscopies increased by about 50% for the gastroenterologist group, the hospital, and the pathology group affiliated with Southlake Family Medicine. Lessons learned: This colorectal cancer screening protocol succeeded in its 3-month trial because it was collaborative, opportunistic, simple, and made good business sense. The protocol is now being implemented at other HealthTexas Provider Network offices. PMID:16278706

  13. [Circulating MicroRNAs as Biomarkers of Colorectal Cancer].

    PubMed

    Umemura, Tsukuru; Kuroki, Chieri

    2015-03-01

    Colorectal cancer is a common tumor in Japan, causing almost 50,000 deaths per year. The development of new biomarkers is strongly desired, in order to detect the early stage of colorectal cancer with high sensitivity and specificity, using less invasive and high through-put methods. miRNA is a small non-coding RNA which regulates gene expression by digesting mRNA or suppressing translation. miRNAs are stable and present in blood, urine, stool, and other body fluids. The profiles of miRNAs in body fluid are specific to pathological states. There is accumulating data showing the usefulness of miRNAs as new biomarkers for colorectal cancer. We summarize the current knowledge in the previous literature (10 plasma analyses: sensitivity: 83.3 to 89%, specificity: 41 to 84.7%, AUC: 0.606 to 0.896; 13 serum analyses: sensitivity: 66.7 to 96.4%, specificity: 63.9 to 88.1%, AUC: 0.679 to 0.918; and 8 fecal analyses: sensitivity: 70.9 to 81.8%, specificity: 68.4 to 96.3%, AUC: 0.64 to 0.829). We focus on the standardization of miRNA analysis, namely: 1) preanalytical processes: difference of miRNA levels between plasma and serum, sampling methods, preparation of plasma or serum, and preservation of samples; 2) analytical processes: mRNA extraction methods, amplification, normalizer, and cut-off values. In conclusion, miRNAs are expected to become new biomarkers for colorectal cancer screening. PMID:26524857

  14. MicroRNAs: promising biomarkers for diagnosis and therapeutic targets in human colorectal cancer metastasis.

    PubMed

    Hur, Keun

    2015-04-01

    Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of cancer-related death worldwide. Distant metastasis is a major cause of mortality in CRC. MicroRNAs (miRNAs) are small non-coding RNA molecules involved in the post-transcriptional and translational regulation of gene expression. Many miRNAs are aberrantly expressed in cancer and influence tumor progression. Accumulating studies suggest that multiple miRNAs are actively involved in the CRC metastasis process. Thus, we aim to introduce the role of miRNAs in multi-steps of CRC metastasis, including cancer cell invasion, intravasation, circulation, extravasation, colonization, angiogenesis, and epithelial-mesenchymal transition (EMT). Moreover, we suggest the potential application of miRNAs as biomarkers for CRC patients with metastasis.

  15. Genetics and Genetic Biomarkers in Sporadic Colorectal Cancer

    PubMed Central

    Carethers, John M.; Jung, Barbara H.

    2015-01-01

    Sporadic colorectal cancer (CRC) is a somatic genetic disease in which pathogenesis is influenced by the local colonic environment and the patient’s genetic background. Consolidating the knowledge of genetic and epigenetic events that occur with initiation, progression, and metastasis of sporadic CRC has identified some biomarkers that might be utilized to predict behavior and prognosis beyond staging, and inform treatment approaches. Modern next generation sequencing of sporadic CRCs has confirmed prior identified genetic alterations, and has classified new alterations. Each patient’s CRC is genetically unique, propelled by 2 to 8 driver gene alterations that have accumulated within the CRC since initiation. Commonly observed alterations across sporadic CRCs have allowed classification into a: (1) hypermutated group that includes defective DNA mismatch repair with microsatellite instability (MSI) and POLE mutations in ~15%, containing multiple frameshifted genes and BRAFV600E; (2) non-hypermutated group with multiple somatic copy number alterations and aneuploidy in ~85%, containing oncogenic activation of KRAS and PIK3CA and mutation and loss of heterozygosity of tumor suppressor genes such as APC and TP53; (3) CpG Island Methylator Phenotype CRCs in ~20% that overlap greatly with MSI CRCs and some non-hypermutated CRCs; and (4) elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) in ~60% that associates with metastatic behavior in both hypermutated and non-hypermutated groups. Components from these classifications are now used as diagnostic, prognostic and treatment biomarkers. Additional common biomarkers may come from genome-wide association studies and microRNAs among other sources, as well as from the unique alteration profile of an individual CRC to apply a precision medicine approach to care. PMID:26216840

  16. DEK over expression as an independent biomarker for poor prognosis in colorectal cancer

    PubMed Central

    2013-01-01

    Background The DEK protein is related to chromatin reconstruction and gene transcription, and plays an important role in cell apoptosis. High expression levels of the human DEK gene have been correlated with numerous human malignancies. This study explores the roles of DEK in tumor progression and as a prognostic determinant of colorectal cancer. Methods Colorectal cancer specimens from 109 patients with strict follow-up, and colorectal adenomas from 52 patients were selected for analysis of DEK protein by immunohistochemistry. The correlations between DEK over expression and the clinicopathological features of colorectal cancers were evaluated by Chi-square test and Fisher’s exact tests. The survival rates were calculated by the Kaplan-Meier method, and the relationship between prognostic factors and patient survival was also analyzed by the Cox proportional hazard models. Results DEK protein showed a nuclear immunohistochemical staining pattern in colorectal cancers. The strongly positive rate of DEK protein was 48.62% (53/109) in colorectal cancers, which was significantly higher than that in either adjacent normal colon mucosa (9.17%, 10/109) or colorectal adenomas (13.46%, 7/52). DEK over expression in colorectal cancers was positively correlated with tumor size, grade, lymph node metastasis, serosal invasion, late stage, and disease-free survival- and 5-year survival rates. Further analysis showed that patients with late stage colorectal cancer and high DEK expression had worse survival rates than those with low DEK expression. Moreover, multivariate analysis showed high DEK expression, serosal invasion, and late stage are significant independent risk factors for mortality in colorectal cancer. Conclusions DEK plays an important role in the progression of colorectal cancers and it is an independent poor prognostic factor of colorectal cancers. PMID:23902796

  17. Beneficial Regulation of Metabolic Profiles by Black Raspberries in Human Colorectal Cancer Patients.

    PubMed

    Pan, Pan; Skaer, Chad W; Stirdivant, Steven M; Young, Matthew R; Stoner, Gary D; Lechner, John F; Huang, Yi-Wen; Wang, Li-Shu

    2015-08-01

    Dietary intervention of freeze-dried black raspberries (BRBs) in a group of human colorectal cancer patients has demonstrated beneficial effects, including proapoptosis, antiproliferation, and antiangiogenesis. The aim of this study was to investigate BRB-mediated metabolite changes from this same cohort of patients. Twenty-eight colorectal cancer patients were given 60 g BRB powder daily for 1 to 9 weeks. Urine and plasma specimens were collected before and after BRB intervention. A mass spectrometry-based nontargeted metabolomic analysis was conducted on each specimen. A total of more than 400 metabolites were annotated in each specimen. Of these 34 and 6 metabolites were significantly changed by BRBs in urine and plasma, respectively. Increased levels of 4-methylcatechol sulfate in both post-BRB urine and post-BRB plasma were significantly correlated with a higher level of apoptotic marker (TUNEL) in post-BRB tumors. One tricarboxylic acid (TCA) cycle metabolites, cis-aconitate, was increased in post-BRB urine. Furthermore, BRB-derived polyphenols were absorbed and metabolized to various benzoate species, which were significantly increased in post-BRB specimens. Increased benzoate levels were positively correlated with enhanced levels of amino acid metabolite. These results suggest that BRBs induce significant metabolic changes and affect energy generating pathways.This study supports the hypothesis that BRBs might be beneficial to colorectal cancer patients through the regulation of multiple metabolites.

  18. Screening for colorectal cancer: possible improvements by risk assessment evaluation?

    PubMed

    Nielsen, Hans J; Jakobsen, Karen V; Christensen, Ib J; Brünner, Nils

    2011-11-01

    Emerging results indicate that screening improves survival of patients with colorectal cancer. Therefore, screening programs are already implemented or are being considered for implementation in Asia, Europe and North America. At present, a great variety of screening methods are available including colono- and sigmoidoscopy, CT- and MR-colonography, capsule endoscopy, DNA and occult blood in feces, and so on. The pros and cons of the various tests, including economic issues, are debated. Although a plethora of evaluated and validated tests even with high specificities and reasonable sensitivities are available, an international consensus on screening procedures is still not established. The rather limited compliance in present screening procedures is a significant drawback. Furthermore, some of the procedures are costly and, therefore, selection methods for these procedures are needed. Current research into improvements of screening for colorectal cancer includes blood-based biological markers, such as proteins, DNA and RNA in combination with various demographically and clinically parameters into a "risk assessment evaluation" (RAE) test. It is assumed that such a test may lead to higher acceptance among the screening populations, and thereby improve the compliances. Furthermore, the involvement of the media, including social media, may add even more individuals to the screening programs. Implementation of validated RAE and progressively improved screening methods may reform the cost/benefit of screening procedures for colorectal cancer. Therefore, results of present research, validating RAE tests, are awaited with interest. PMID:21854094

  19. Inducible Nitric Oxide Synthase Expression in Human Colorectal Cancer

    PubMed Central

    Cianchi, Fabio; Cortesini, Camillo; Fantappiè, Ornella; Messerini, Luca; Schiavone, Nicola; Vannacci, Alfredo; Nistri, Silvia; Sardi, Iacopo; Baroni, Gianna; Marzocca, Cosimo; Perna, Federico; Mazzanti, Roberto; Bechi, Paolo; Masini, Emanuela

    2003-01-01

    To investigate the potential involvement of the nitric oxide (NO) pathway in colorectal carcinogenesis, we correlated the expression and the activity of inducible nitric oxide synthase (iNOS) with the degree of tumor angiogenesis in human colorectal cancer. Tumor samples and adjacent normal mucosa were obtained from 46 surgical specimens. Immunohistochemical expression of iNOS, vascular endothelial growth factor (VEGF), and CD31 was analyzed on paraffin-embedded tissue sections. iNOS activity and cyclic GMP levels were assessed by specific biochemical assays. iNOS protein expression was determined by Western blot analysis. iNOS and VEGF mRNA levels were evaluated using Northern blot analysis. Both iNOS and VEGF expressions correlated significantly with intratumor microvessel density (rs = 0.31, P = 0.02 and rs = 0.67, P < 0.0001, respectively). A significant correlation was also found between iNOS and VEGF expression (P = 0.001). iNOS activity and cyclic GMP production were significantly higher in the cancer specimens than in the normal mucosa (P < 0.0001 and P < 0.0001, respectively), as well as in metastatic tumors than in nonmetastatic ones (P = 0.002 and P = 0.04, respectively). Western and Northern blot analyses confirmed the up-regulation of the iNOS protein and gene in the tumor specimens as compared with normal mucosa. NO seems to play a role in colorectal cancer growth by promoting tumor angiogenesis. PMID:12598314

  20. Nrf2 as a Chemopreventive Target in Colorectal Cancer

    PubMed Central

    Saw, Constance Lay Lay; Kong, Tony Ah-Ng

    2012-01-01

    Introduction Numerous epidemiological studies have linked consumption of cruciferous vegetables to a reduced risk of colorectal cancer (CRC) in individuals. It is currently well accepted that chronic inflammation is a contributing factor in 15-20% malignancies including CRC. Many chemopreventive compounds are effective in preclinical systems and many on-going clinical trials are showing promising findings. Many of these compounds could activate the antioxidant responsive element (ARE), a critical regulatory element for phase II protective/detoxification and anti-oxidative stress enzymes mediated by nuclear factor-erythroid 2-related factor 2 (Nrf2). Recently, Nrf2 has emerged as a novel target for the prevention of CRC. Areas covered A full literature search was performed using PubMed with the key words ‘ARE, Nrf2, colon, colorectal cancer, chemoprevention, cancer prevention’, and all relevant publications are included. Expert opinion The use of Nrf2 knockout mice has provided key insights into the toxicological and chemopreventive importance of this pathway. Mounting evidence has revealed that Nrf2 is a critical regulator of inflammation as well, a major driving force for CRC progression and formation. Targeting the Nrf2/ARE pathway may present a novel therapeutic approach for the treatment of not only colorectal inflammatory diseases but the frequent subsequent development of CRC as well. PMID:21261563

  1. Acetylsalicylic Acid and Eflornithine in Treating Patients at High Risk for Colorectal Cancer | Division of Cancer Prevention

    Cancer.gov

    This phase II trial is studying how well giving acetylsalicylic acid together with eflornithine works in treating patients at high risk for colorectal cancer. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of acetylsalicylic acid and eflornithine may prevent colorectal cancer. |

  2. Can We Select Patients for Colorectal Cancer Prevention with Aspirin?

    PubMed

    Kraus, Sarah; Sion, Daniel; Arber, Nadir

    2015-01-01

    Aspirin has been extensively investigated in the context of the prevention of cardiovascular disease. It has one of the strongest cumulative evidence supporting its use in colorectal cancer (CRC) chemoprevention. Epidemiological, clinical, and observational studies have demonstrated that aspirin and non-steroidal antiinflammatory drugs (NSAIDs), including COX-2 inhibitors, can protect against CRC and significantly reduce its incidence. Moreover, prospective randomized controlled trials of colorectal polyp recurrence and in patients with hereditary CRC syndromes have shown that aspirin can produce regression of existing colorectal adenomas and prevent the formation of new polyps. However, the lowest effective doses, treatment duration, target populations, and the effects on survival are not entirely clear. Although not common serious side effects and in particular gastrointestinal and intracerebral hemorrhage do occur, better selection of individuals who might benefit the most from aspirin use must be carefully performed in order to maximize their risk/benefit ratio. In the era of precision medicine, genetic information, blood and/or urinary biomarkers, could potentially help in tailoring chemopreventive therapeutic strategies, based on aspirin use, while limiting adverse toxic effects. The current review will cover the use of aspirin for the prevention of colorectal adenomas and CRC, potential markers for chemoprevention, and patient stratification. PMID:26369678

  3. Decreased MALL expression negatively impacts colorectal cancer patient survival

    PubMed Central

    Cui, Feifei; Sun, Xing; Zhong, Lin; Yan, Dongwang; Zhou, Chongzhi; Deng, Guilong; Wang, Bin; Qi, Xiaosheng; Wang, Shuyun; Qu, Lei; Deng, Biao; Pan, Ming; Chen, Jian; Wang, Yupeng; Song, Guohe; Tang, Huamei; Zhou, Zongguang; Peng, Zhihai

    2016-01-01

    The aim of the present study was to determine whether MALL expression is associated with colon cancer progression and patient survival. MALL mRNA expression was reduced in the tumor tissues of 70% of the colon cancer patients and 75% of the rectal cancer patients as compared to their normal tissues. MALL protein was also significantly reduced in the tumor tissues of colon cancer patients (P < 0.001). Increased LOH and methylation of MALL was observed in tumor tissues as compared to normal tissues. Reduced MALL expression was associated with vessin invasion, disease recurrence and metastasis or death (P ≤ 0.027). Furthermore, patients with MALL-negative tumors had significantly decreased overall survival (OS) and disease-free survival (DFS) (P < 0.008 and P < 0.011, respectively). Univariate analysis indicated that MALL expression was significantly associated with OS and DFS. Finally, overexpression of MALL suppressed HCT116 and SW480 cell proliferation and inhibited HCT116 migration. MALL may play a role in colorectal cancer progression as suppression of its expression in tumor tissues negatively impacts colorectal cancer patient survival. Further analyses are required to determine if reduced MALL expression is due to LOH and/or methylation. PMID:26992238

  4. Vitamin D Receptor Gene Polymorphism and the Risk of Colorectal Cancer: A Nested Case-Control Study

    PubMed Central

    Budhathoki, Sanjeev; Yamaji, Taiki; Iwasaki, Motoki; Sawada, Norie; Shimazu, Taichi; Sasazuki, Shizuka; Yoshida, Teruhiko; Tsugane, Shoichiro

    2016-01-01

    Epidemiological and experimental evidence suggest that vitamin D is protective against the risk of colorectal cancer. Polymorphisms in the gene encoding vitamin D receptor (VDR), which mediates most of the known cellular effects of vitamin D, have been suggested to alter this association. Here, using a tag SNP approach, we comprehensively evaluated the role of common genetic variants in VDR and their interaction with plasma vitamin D levels in relation to colorectal cancer risk in Japanese populations. A total of 356 colorectal cancer cases and 709 matched control subjects were selected from the participants of the Japan Public Health Center-based Prospective Cohort Study. Among these subjects, 29 VDR single nucleotide polymorphisms (SNPs) were selected and genotyped, and plasma vitamin D concentrations were measured. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of colorectal cancer, with adjustment for potential confounding factors. Among the results, eight VDR SNPs, namely rs2254210, rs1540339, rs2107301, rs11168267, rs11574113, rs731236, rs3847987 and rs11574143, the latter 5 of which were located in the 3′ region, were nominally associated with the risk of colorectal cancer (P = 0.01–0.048). Furthermore, of the above 5 3′ region SNPs, the inverse associations for 3 SNPs (rs11574113, rs3847987 and rs11574143) appeared to be evident only in those with high plasma vitamin D concentration. However, neither of these direct and suggestive interaction analysis associations was significant after multiple testing adjustment. Overall, the findings of this study provide only limited support for an association between common genetic variations in VDR and colorectal cancer risk in the Japanese population. PMID:27736940

  5. Does colon cancer ever metastasize to bone first? a temporal analysis of colorectal cancer progression

    PubMed Central

    2009-01-01

    Background It is well recognized that colorectal cancer does not frequently metastasize to bone. The aim of this retrospective study was to establish whether colorectal cancer ever bypasses other organs and metastasizes directly to bone and whether the presence of lung lesions is superior to liver as a better predictor of the likelihood and timing of bone metastasis. Methods We performed a retrospective analysis on patients with a clinical diagnosis of colon cancer referred for staging using whole-body 18F-FDG PET and CT or PET/CT. We combined PET and CT reports from 252 individuals with information concerning patient history, other imaging modalities, and treatments to analyze disease progression. Results No patient had isolated osseous metastasis at the time of diagnosis, and none developed isolated bone metastasis without other organ involvement during our survey period. It took significantly longer for colorectal cancer patients to develop metastasis to the lungs (23.3 months) or to bone (21.2 months) than to the liver (9.8 months). Conclusion: Metastasis only to bone without other organ involvement in colorectal cancer patients is extremely rare, perhaps more rare than we previously thought. Our findings suggest that resistant metastasis to the lungs predicts potential disease progression to bone in the colorectal cancer population better than liver metastasis does. PMID:19664211

  6. Synergistic anticancer activity of capsaicin and 3,3'-diindolylmethane in human colorectal cancer.

    PubMed

    Clark, Ruth; Lee, Jihye; Lee, Seong-Ho

    2015-05-01

    Cancer is a leading cause of morbidity and mortality worldwide. A promising area of cancer research is focused on chemoprevention by nutritional compounds. Epidemiological studies have shown a strong negative correlation between fruit, vegetable, and spice intake and rates of cancer. Although individual active compounds have demonstrated significant anticancer activity, an emerging area of research is focusing on the combination of multiple dietary compounds that act synergistically on cancer to exert greater effects. The current study evaluated the potential synergistic effects of capsaicin, an active compound from red chili peppers, in combination with 3,3'-diindolylmethane (DIM), from cruciferous vegetables. A synergistic induction of apoptosis and inhibition of cell proliferation was observed in human colorectal cancer cells treated with the combination of capsaicin and DIM. It was also observed that these two compounds activated transcriptional activity of NF-κB and p53 synergistically. Combination treatment stabilized nuclear p53 and up- or down-regulated expression of several target genes that are downstream of NF-κB and p53. The present study suggests capsaicin and DIM work synergistically to inhibit cell proliferation and induce apoptosis in colorectal cancer through modulating transcriptional activity of NF-κB, p53, and target genes associated with apoptosis. PMID:25876645

  7. Synergistic anticancer activity of capsaicin and 3,3'-diindolylmethane in human colorectal cancer.

    PubMed

    Clark, Ruth; Lee, Jihye; Lee, Seong-Ho

    2015-05-01

    Cancer is a leading cause of morbidity and mortality worldwide. A promising area of cancer research is focused on chemoprevention by nutritional compounds. Epidemiological studies have shown a strong negative correlation between fruit, vegetable, and spice intake and rates of cancer. Although individual active compounds have demonstrated significant anticancer activity, an emerging area of research is focusing on the combination of multiple dietary compounds that act synergistically on cancer to exert greater effects. The current study evaluated the potential synergistic effects of capsaicin, an active compound from red chili peppers, in combination with 3,3'-diindolylmethane (DIM), from cruciferous vegetables. A synergistic induction of apoptosis and inhibition of cell proliferation was observed in human colorectal cancer cells treated with the combination of capsaicin and DIM. It was also observed that these two compounds activated transcriptional activity of NF-κB and p53 synergistically. Combination treatment stabilized nuclear p53 and up- or down-regulated expression of several target genes that are downstream of NF-κB and p53. The present study suggests capsaicin and DIM work synergistically to inhibit cell proliferation and induce apoptosis in colorectal cancer through modulating transcriptional activity of NF-κB, p53, and target genes associated with apoptosis.

  8. Microsatellite instability and the clinicopathological features of sporadic colorectal cancer

    PubMed Central

    Ward, R; Meagher, A; Tomlinson, I; O'Connor, T; Norrie, M; Wu, R; Hawkins, N

    2001-01-01

    BACKGROUND AND AIMS—In this study, we prospectively examined the clinical significance of the microsatellite instability (MSI) phenotype in sporadic colorectal cancer, and investigated methods for effective identification of these tumours in routine pathology practice.
METHODS—DNA was extracted from 310 tumours collected from 302 consecutive individuals undergoing curative surgery for sporadic colorectal cancer. Microsatellite status was determined by polymerase chain reaction amplification using standard markers, while immunostaining was used to examine expression of MLH1, MSH2, and p53.
RESULTS—Eleven per cent of tumours showed high level instability (MSI-H), 6.8% had low level instability (MSI-L), and the remainder were stable. MSI-H tumours were significantly more likely to be of high histopathological grade, have a mucinous phenotype, and to harbour increased numbers of intraepithelial lymphocytes. They were also more likely to be right sided, occur in women, and be associated with improved overall survival. In total, 25 (8%) tumours showed loss of staining for MLH1 and a further three tumours showed absence of staining for MSH2. The positive and negative predictive value of immunohistochemistry in the detection of MSI-H tumours was greater than 95%.
CONCLUSIONS—We conclude that the MSI-H phenotype constitutes a pathologically and clinically distinct subtype of sporadic colorectal cancer. Immunohistochemical staining for MLH1 and MSH2 represents an inexpensive and accurate means of identifying such tumours.


Keywords: colorectal carcinoma; microsatellite instability; survival; MLH1; MSH2; immunohistochemistry PMID:11358903

  9. Exploring Different Strategies for Efficient Delivery of Colorectal Cancer Therapy

    PubMed Central

    Lin, Congcong; Ng, Huei Leng Helena; Pan, Weisan; Chen, Hubiao; Zhang, Ge; Bian, Zhaoxiang; Lu, Aiping; Yang, Zhijun

    2015-01-01

    Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer death in the world. Currently available chemotherapy of CRC usually delivers the drug to both normal as well as cancerous tissues, thus leading to numerous undesirable effects. Much emphasis is being laid on the development of effective drug delivery systems for achieving selective delivery of the active moiety at the anticipated site of action with minimized unwanted side effects. Researchers have employed various techniques (dependent on pH, time, pressure and/or bacteria) for targeting drugs directly to the colonic region. On the other hand, systemic drug delivery strategies to specific molecular targets (such as FGFR, EGFR, CD44, EpCAM, CA IX, PPARγ and COX-2) overexpressed by cancerous cells have also been shown to be effective. This review aims to put forth an overview of drug delivery technologies that have been, and may be developed, for the treatment of CRC. PMID:26569228

  10. Microbiota regulation of inflammatory bowel disease and colorectal cancer

    PubMed Central

    Liu, Zhanju; Cao, Anthony T.; Cong, Yingzi

    2013-01-01

    The host and microbiota have evolved mechanisms for coexistence over millions of years. Accumulating evidence indicates that a dynamic mutualism between the host and the commensal microbiota has important implications for health, and microbial colonization contributes to the maintenance of intestinal immune homeostasis. However, alterations in communication between the mucosal immune system and gut microbial communities have been implicated as the core defect that leads to chronic intestinal inflammation and cancer development. We will discuss the recent progress on how gut microbiota regulates intestinal homeostasis and the pathogenesis of inflammatory bowel disease and colorectal cancer. PMID:24071482

  11. Characterization of Colorectal Cancer Development in Apc (min/+) Mice.

    PubMed

    Nalbantoglu, ILKe; Blanc, Valerie; Davidson, Nicholas O

    2016-01-01

    The Apc (min/+) mouse provides an excellent experimental model for studying genetic, environmental, and therapeutic aspects of intestinal neoplasia in humans. In this chapter, we will describe techniques for studying colon cancer development in Apc (min/+) mice on C57BL/6J (B6) background, focusing on the roles of environmental modifiers, including Dextran Sulfate Sodium (DSS), high fat diet, and bile acid supplementation in the context of experimental colorectal cancer. This chapter also includes protocols describing extraction and purification of DSS-contaminated RNA, as well as sampling, harvesting, and tissue processing. The common pathologic lesions encountered in these animals are described in detail. PMID:27246043

  12. Advances in glucose metabolism research in colorectal cancer

    PubMed Central

    Fang, Sitian; Fang, Xiao

    2016-01-01

    Cancer cells uptake glucose at a higher rate and produce lactic acid rather than metabolizing pyruvate through the tricarboxylic acid cycle. This adaptive metabolic shift is termed the Warburg effect. Recently progress had been made regarding the mechanistic understanding of glucose metabolism and associated diagnostic and therapeutic methods, which have been investigated in colorectal cancer. The majority of novel mechanisms involve important glucose metabolism associated genes and miRNA regulation. The present review discusses the contribution of these research results to facilitate with the development of novel diagnosis and anticancer treatment options. PMID:27602209

  13. Aspirin and colorectal cancer: the promise of precision chemoprevention.

    PubMed

    Drew, David A; Cao, Yin; Chan, Andrew T

    2016-03-01

    Aspirin (acetylsalicylic acid) has become one of the most commonly used drugs, given its role as an analgesic, antipyretic and agent for cardiovascular prophylaxis. Several decades of research have provided considerable evidence demonstrating its potential for the prevention of cancer, particularly colorectal cancer. Broader clinical recommendations for aspirin-based chemoprevention strategies have recently been established; however, given the known hazards of long-term aspirin use, larger-scale adoption of an aspirin chemoprevention strategy is likely to require improved identification of individuals for whom the protective benefits outweigh the harms. Such a precision medicine approach may emerge through further clarification of aspirin's mechanism of action. PMID:26868177

  14. Advances in glucose metabolism research in colorectal cancer

    PubMed Central

    Fang, Sitian; Fang, Xiao

    2016-01-01

    Cancer cells uptake glucose at a higher rate and produce lactic acid rather than metabolizing pyruvate through the tricarboxylic acid cycle. This adaptive metabolic shift is termed the Warburg effect. Recently progress had been made regarding the mechanistic understanding of glucose metabolism and associated diagnostic and therapeutic methods, which have been investigated in colorectal cancer. The majority of novel mechanisms involve important glucose metabolism associated genes and miRNA regulation. The present review discusses the contribution of these research results to facilitate with the development of novel diagnosis and anticancer treatment options.

  15. Colorectal cancer: response to sunitinib in a heavily pretreated colorectal cancer patient.

    PubMed

    Blesa, Joan Manel Gasent; Pulido, Enrique Grande

    2010-01-01

    A 64-year-old man was admitted to the emergency room in May 2000 due to pelvic pain, functional disability of the lower limb, and bleeding from a rectal fistula. The patient was diagnosed with a rectum-sigma adenocarcinoma (pT1N0M0 stage). After surgery by left hemicolectomy, the patient received adjuvant chemotherapy with tegafur for 6 months. Due to the development of subsequent recurrences (infravesical relapse, bone and lung progression) associated with CEA progression and pain worsening, the patient received treatment by every available agent for the metastatic colorectal cancer, including oxaliplatin and radiotherapy; irinotecan; FOLFOX schema; oral capecitabine; raltitrexed; irinotecan and cetuximab; cetuximab as a single agent; always in combination with zolendronic acid-based treatment for pain control. Once the patient had progressed to all the approved drugs available in the market, sunitinib (50mg/day given for 4 weeks followed by 2 weeks of rest) was proposed as compassionate use. The patient received sunitinib for a total of 6 months (four cycles). On account of the nonmeasurable disease nature of the metastatic presentation in the present case, the clinical benefit was measured in terms of reduction of painkiller intake, improvement in performance status of the patient, and CEA serum levels. In addition to all of these clinical and biological data, CT images showed an increase in necrotic area of the bone lesion without any decrease in tumor size by classical RECIST criteria. The patient is still under sunitinib treatment and has recovered his normal daily activity.

  16. Red meat consumption and cancer: reasons to suspect involvement of bovine infectious factors in colorectal cancer.

    PubMed

    zur Hausen, Harald

    2012-06-01

    An increased risk for colorectal cancer has been consistently reported for long-time consumption of cooked and processed red meat. This has frequently been attributed to chemical carcinogens arising during the cooking process of meat. Long-time fish or poultry consumption apparently does not increase the risk, although similar or higher concentrations of chemical carcinogens were recorded in their preparation for consumption. The geographic epidemiology of colorectal cancer seems to correspond to regions with a high rate of beef consumption. Countries with a virtual absence of beef in the diet (India) or where preferably lamb or goat meat is consumed (several Arabic countries) reveal low rates of colorectal cancer. In China, pork consumption has a long tradition, with an intermediate colorectal cancer rate. In Japan and Korea, large scale beef and pork imports started after World War II or after the Korean War. A steep rise in colorectal cancer incidence was noted after 1970 in Japan and 1990 in Korea. The consumption of undercooked beef (e.g., shabu-shabu, Korean yukhoe and Japanese yukke) became very popular in both countries. The available data are compatible with the interpretation that a specific beef factor, suspected to be one or more thermoresistant potentially oncogenic bovine viruses (e.g., polyoma-, papilloma- or possibly single-stranded DNA viruses) may contaminate beef preparations and lead to latent infections in the colorectal tract. Preceding, concomitant or subsequent exposure to chemical carcinogens arising during cooking procedures should result in increased risk for colorectal cancer synergistic with these infections.

  17. Red meat consumption and cancer: reasons to suspect involvement of bovine infectious factors in colorectal cancer.

    PubMed

    zur Hausen, Harald

    2012-06-01

    An increased risk for colorectal cancer has been consistently reported for long-time consumption of cooked and processed red meat. This has frequently been attributed to chemical carcinogens arising during the cooking process of meat. Long-time fish or poultry consumption apparently does not increase the risk, although similar or higher concentrations of chemical carcinogens were recorded in their preparation for consumption. The geographic epidemiology of colorectal cancer seems to correspond to regions with a high rate of beef consumption. Countries with a virtual absence of beef in the diet (India) or where preferably lamb or goat meat is consumed (several Arabic countries) reveal low rates of colorectal cancer. In China, pork consumption has a long tradition, with an intermediate colorectal cancer rate. In Japan and Korea, large scale beef and pork imports started after World War II or after the Korean War. A steep rise in colorectal cancer incidence was noted after 1970 in Japan and 1990 in Korea. The consumption of undercooked beef (e.g., shabu-shabu, Korean yukhoe and Japanese yukke) became very popular in both countries. The available data are compatible with the interpretation that a specific beef factor, suspected to be one or more thermoresistant potentially oncogenic bovine viruses (e.g., polyoma-, papilloma- or possibly single-stranded DNA viruses) may contaminate beef preparations and lead to latent infections in the colorectal tract. Preceding, concomitant or subsequent exposure to chemical carcinogens arising during cooking procedures should result in increased risk for colorectal cancer synergistic with these infections. PMID:22212999

  18. MicroRNA 196B regulates FAS-mediated apoptosis in colorectal cancer cells

    PubMed Central

    Kang, In-Hong; Park, Won Cheol; Seo, Geom-Seog; Choi, Suck-Chei; Kim, Hun-Soo; Moon, Hyung-Bae; Yun, Ki-Jung; Chae, Soo-Cheon

    2015-01-01

    Using miRNA microarray analysis, we identified 31 miRNAs that were significantly up-regulated or down-regulated in colon cancer tissues. We chose MIR196B, which was specifically up-regulated in colon cancer, for further study. We identified 18 putative MIR196B target genes by comparing between the mRNAs down-regulated in MIR196B-overexpressed cells and the assumed MIR196B target genes predicted by public bioinformatics tools. The association between MIR196B and FAS was verified in this study. FAS expression was constitutively elevated in normal human colorectal tissues. However, its expression was often reduced in human colorectal cancer. The decrease in FAS expression could be responsible for the reduction of apoptosis in colorectal cancer cells. In colorectal cancer tissue, we showed that MIR196B up-regulation was mutually followed by down regulation of FAS expression. We also showed that MIR196B directly repressed FAS expression in colorectal cells. Furthermore, anti-MIR196B up-regulated FAS expression and increased apoptosis in colorectal cancer cell lines. Our results suggest that the up-regulation of MIR196B modulates apoptosis in colorectal cancer cells by partially repressing FAS expression and that anti-MIR196B could be a potential candidate as an anti-cancer drug in colorectal cancer therapy. PMID:25605245

  19. Cell-based Immunotherapy for Colorectal Cancer with Cytokine-induced Killer Cells

    PubMed Central

    Kim, Ji Sung; Kim, Yong Guk; Park, Eun Jae; Kim, Boyeong; Lee, Hong Kyung; Hong, Jin Tae; Kim, Youngsoo

    2016-01-01

    Colorectal cancer is the third leading cancer worldwide. Although incidence and mortality of colorectal cancer are gradually decreasing in the US, patients with metastatic colorectal cancer have poor prognosis with an estimated 5-year survival rate of less than 10%. Over the past decade, advances in combination chemotherapy regimens for colorectal cancer have led to significant improvement in progression-free and overall survival. However, patients with metastatic disease gain little clinical benefit from conventional therapy, which is associated with grade 3~4 toxicity with negative effects on quality of life. In previous clinical studies, cell-based immunotherapy using dendritic cell vaccines and sentinel lymph node T cell therapy showed promising therapeutic results for metastatic colorectal cancer. In our preclinical and previous clinical studies, cytokine-induced killer (CIK) cells treatment for colorectal cancer showed favorable responses without toxicities. Here, we review current treatment options for colorectal cancer and summarize available clinical studies utilizing cell-based immunotherapy. Based on these studies, we recommend the use CIK cell therapy as a promising therapeutic strategy for patients with metastatic colorectal cancer. PMID:27162526

  20. Possible Role of Cancer Stem Cells in Colorectal Cancer Metastasizing to the Liver.

    PubMed

    Jiao, Zuo-Yi; Cao, Hong-Tai; Li, Yu-Min

    2016-01-01

    Colorectal cancer (CRC) is one of the most common cancers in the world. In recent decades, drug therapy and surgery have not achieved satisfactory results in curing CRC. The identification of cancer stem cells (CSCs) has provided a possible mechanistic explanation of CRC growth and metastasis. Traditional chemotherapy targets rapidly dividing cells, and since the CSCs can escape these therapies and become circulating cells, CSCs may be responsible for cancer relapse and metastasis. A better understanding of the roles of CSCs in the pathogenesis of primary CRC and its metastasis, as well as how these CSCs are regulated at the molecular level, is of paramount importance. In this review, we summarize the current understanding of the role of colorectal CSCs in CRC liver metastasis, and provide some insights on the potential implication of colorectal CSCs to better design therapeutic regimens and prevent CRC metastasis. PMID:26832139

  1. Evolution of the management of colorectal cancer using integrative medicine.

    PubMed

    Li, Shao-Tang; Chi, Pan

    2011-01-01

    Colorectal cancer (CRC) remains one of the major causes of cancer death worldwide. In recent years, the development of new and effective management options, such as fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET), total mesorectal excision (TME) and monoclonal antibody novel "targeted" therapies has led to a considerable improvement in the outcome of this disease. In China, studies on CRC using integrative medicine (IM) have made remarkable progress. We therefore review the recent developments in CRC treatment through IM and Western medicine, including research studies such as the exploitation of Chinese herbs for the disruption of the tumor cell cycle or inhibition of tumor cell proliferation, induction of tumor cell apoptosis, improvement of the immune system, and the curative effect of chemotherapy. We also examine clinical studies such as those on special prescriptions and medicines and IM in anti-cancer therapy. Particularly, we analyze the advantages and disadvantages of management with IM, and propose a suggestion for the management of colorectal cancer with IM, such as screening for effective prescriptions. We also analyze Chinese medicine, studying the pharmacologic mechanism of its anti-cancer effect, further strengthening the study of IM on CRC.

  2. Serum 25-hydroxyvitamin D, vitamin D binding protein, and risk of colorectal cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

    PubMed Central

    Weinstein, Stephanie J.; Purdue, Mark P.; Smith-Warner, Stephanie A.; Mondul, Alison M.; Black, Amanda; Ahn, Jiyoung; Huang, Wen-Yi; Horst, Ronald L.; Kopp, William; Rager, Helen; Ziegler, Regina G.; Albanes, Demetrius

    2014-01-01

    The potential role of vitamin D in cancer prevention has generated substantial interest, and laboratory experiments indicate several anti-cancer properties for vitamin D compounds. Prospective studies of circulating 25-hydroxyvitamin D [25(OH)D], the accepted biomarker of vitamin D status, suggest an inverse association with colorectal cancer risk, but with some inconsistencies. Furthermore, the direct or indirect impact of the key transport protein, vitamin D binding protein (DBP), has not been examined. We conducted a prospective study of serum 25(OH)D and DBP concentrations and colorectal cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, based on 476 colorectal cancer cases and 476 controls, matched on age, sex, race, and date of serum collection. All subjects underwent sigmoidoscopic screening at baseline and once during follow-up. Conditional logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Circulating 25(OH)D was inversely associated with colorectal cancer (OR=0.60, 95% CI 0.38-0.94 for highest versus lowest quintile, p-trend 0.01). Adjusting for recognized colorectal cancer risk factors and accounting for seasonal vitamin D variation did not alter the findings. Neither circulating DBP nor the 25(OH)D:DBP molar ratio, a proxy for free circulating 25(OH)D, was associated with risk (OR=0.82, 95% CI 0.54-1.26, and OR=0.79, 95% CI 0.52-1.21, respectively), and DBP did not modify the 25(OH)D association. The current study eliminated confounding by colorectal cancer screening behavior, and supports an association between higher vitamin D status and substantially lower colorectal cancer risk, but does not indicate a direct or modifying role for DBP. PMID:25156182

  3. Nanoscale/Molecular analysis of Fecal Colonocytes for Colorectal Cancer Screening | Division of Cancer Prevention

    Cancer.gov

    DESCRIPTION (provided by applicant): Existing guidelines recommend colorectal cancer (CRC) screening for all patients over age 50. However, CRC remains the second leading cause of cancer death among Americans largely because colonoscopic screening of all the >100 million Americans over age 50 is unfeasible for both patient-related (non-compliance) and societal (inadequate endoscopic capacity and funding) reasons. |

  4. Colorectal cancer screening with odour material by canine scent detection

    PubMed Central

    Kohnoe, Shunji; Yamazato, Tetsuro; Satoh, Yuji; Morizono, Gouki; Shikata, Kentaro; Morita, Makoto; Watanabe, Akihiro; Morita, Masaru; Kakeji, Yoshihiro; Inoue, Fumio; Maehara, Yoshihiko

    2011-01-01

    Objective Early detection and early treatment are of vital importance to the successful treatment of various cancers. The development of a novel screening method that is as economical and non-invasive as the faecal occult blood test (FOBT) for early detection of colorectal cancer (CRC) is needed. A study was undertaken using canine scent detection to determine whether odour material can become an effective tool in CRC screening. Design Exhaled breath and watery stool samples were obtained from patients with CRC and from healthy controls prior to colonoscopy. Each test group consisted of one sample from a patient with CRC and four control samples from volunteers without cancer. These five samples were randomly and separately placed into five boxes. A Labrador retriever specially trained in scent detection of cancer and a handler cooperated in the tests. The dog first smelled a standard breath sample from a patient with CRC, then smelled each sample station and sat down in front of the station in which a cancer scent was detected. Results 33 and 37 groups of breath and watery stool samples, respectively, were tested. Among patients with CRC and controls, the sensitivity of canine scent detection of breath samples compared with conventional diagnosis by colonoscopy was 0.91 and the specificity was 0.99. The sensitivity of canine scent detection of stool samples was 0.97 and the specificity was 0.99. The accuracy of canine scent detection was high even for early cancer. Canine scent detection was not confounded by current smoking, benign colorectal disease or inflammatory disease. Conclusions This study shows that a specific cancer scent does indeed exist and that cancer-specific chemical compounds may be circulating throughout the body. These odour materials may become effective tools in CRC screening. In the future, studies designed to identify cancer-specific volatile organic compounds will be important for the development of new methods for early detection of CRC

  5. [Colorectal cancer in children: report of three cases].

    PubMed

    Vásquez, Liliana; Oscanoa, Mónica; Maza, Iván; Gerónimo, Jenny; Tarrillo, Fanny; Latorre, Alan; Frisancho, Oscar; Llatas, Juan

    2014-07-01

    Colorectal cancer (CRC) is extremely infrequent in children and adolescents. There is little information about this entity, mainly case reports and review articles. We describe three cases of children with poor-differentiated colorectal carcinoma and advanced disease at onset. The presenting symptoms were abdominal pain and constipation, with a median of latency of symptoms of 4-48 months. None of these patients had operable disease at onset; having a disease progression despite therapy in two cases. This study reaffirms poor prognosis of pediatric CRC, probably due to an aggressive tumoral biology and advanced stage at diagnosis. Therapeutic guidelines are based in adult treatment; therefore, efforts should be made to improve tools in early diagnosis and future therapies for a better survival in childhood. PMID:25293994

  6. [Colonoscopy quality control as a requirement of colorectal cancer screening].

    PubMed

    Quintero, Enrique; Alarcón-Fernández, Onofre; Jover, Rodrigo

    2013-11-01

    The strategies used in population-based colorectal screening strategies culminate in colonoscopy and consequently the success of these programs largely depends on the quality of this diagnostic test. The main factors to consider when evaluating quality are scientific-technical quality, safety, patient satisfaction, and accessibility. Quality indicators allow variability among hospitals, endoscopy units and endoscopists to be determined and can identify those not achieving recommended standards. In Spain, the working group for colonoscopy quality of the Spanish Society of Gastroenterology and the Spanish Society of Gastrointestinal Endoscopy have recently drawn up a Clinical Practice Guideline that contains the available evidence on the quality of screening colonoscopy, as well as the basic requirements that must be met by endoscopy units and endoscopists carrying out this procedure. The implementation of training programs and screening colonoscopy quality controls are strongly recommended to guarantee the success of population-based colorectal cancer screening.

  7. Metabolic and Community Synergy of Oral Bacteria in Colorectal Cancer

    PubMed Central

    Baxter, Nielson T.

    2016-01-01

    ABSTRACT The oral periodontopathic bacterium Fusobacterium nucleatum has been repeatedly associated with colorectal tumors. Molecular analysis has identified specific virulence factors that promote tumorigenesis in the colon. However, other oral community members, such as members of the Porphyromonas spp., are also found with F. nucleatum on colonic tumors, and thus, narrow studies of individual pathogens do not take community-wide virulence properties into account. A broader view of oral bacterial physiology and pathogenesis identifies two factors that could promote colonization and persistence of oral bacterial communities in the colon. The polymicrobial nature of oral biofilms and the asaccharolytic metabolism of many of these species make them well suited to life in the microenvironment of colonic lesions. Consideration of these two factors offers a novel perspective on the role of oral microbiota in the initiation, development, and treatment of colorectal cancer. PMID:27303740

  8. Identification of the sAPRIL Binding Peptide and Its Growth Inhibition Effects in the Colorectal Cancer Cells

    PubMed Central

    Liu, Fang; Li, Jing; He, Mei-rong

    2015-01-01

    Background A proliferation-inducing ligand (APRIL) is a member of the tumor necrosis factor (TNF) super family. It binds to its specific receptors and is involved in multiple processes during tumorigenesis and tumor cells proliferation. High levels of APRIL expression are closely correlated to the growth, metastasis, and 5-FU drug resistance of colorectal cancer. The aim of this study was to identify a specific APRIL binding peptide (BP) able to block APRIL activity that could be used as a potential treatment for colorectal cancer. Methods A phage display library was used to identify peptides that bound selectively to soluble recombinant human APRIL (sAPRIL). The peptides with the highest binding affinity for sAPRIL were identified using ELISA. The effects of sAPRIL-BP on cell proliferation and cell cycle/apoptosis in vitro were evaluated using the CCK-8 assay and flow cytometry, respectively. An in vivo mouse model of colorectal cancer was used to determine the anti-tumor efficacy of the sAPRIL-BP. Results Three candidate peptides were characterized from eight phage clones with high binding affinity for sAPRIL. The peptide with the highest affinity was selected for further characterization. The identified sAPRIL-BP suppressed tumor cell proliferation and cell cycle progression in LOVO cells in a dose-dependent manner. In vivo in a mouse colorectal challenge model, the sAPRIL-BP reduced the growth of tumor xenografts in nude mice by inhibiting proliferation and inducing apoptosis intratumorally. Moreover, in an in vivo metastasis model, sAPRIL-BP reduced liver metastasis of colorectal cancer cells. Conclusions sAPRIL-BP significantly suppressed tumor growth in vitro and in vivo and might be a candidate for treating colorectal cancers that express high levels of APRIL. PMID:25826583

  9. Marine n-3 and saturated fatty acids in relation to risk of colorectal cancer in Singapore Chinese: A prospective study

    PubMed Central

    Butler, Lesley M.; Wang, Renwei; Koh, Woon-Puay; Stern, Mariana C.; Yuan, Jian-Min; Yu, Mimi C.

    2009-01-01

    Experimental data support multiple roles for fatty acids in colorectal carcinogenesis. We examined dietary fatty acids and incidence of colorectal cancer, and evaluated effect modification by sex and stage of disease among a population-based cohort of 61,321 Singapore Chinese that was established between 1993 and 1998. As of December 31, 2005, 961 incident colorectal cancers were diagnosed. Presented hazard ratios (HRs) are for highest versus lowest quartiles with adjustment for potential confounders. Among women, we observed a dose-dependent, positive association between saturated fat and localized colorectal cancer (Dukes A or B) [(HR = 1.69, 95% confidence interval (CI) = 1.08–2.63, p for trend = 0.01)]. No such associations were noted in men (p for interaction by sex = 0.04). Marine n-3 polyunsaturated fatty acid (PUFA) intake was positively associated with advanced disease (Dukes C or D) (HR = 1.33, 95% CI = 1.05–1.70, p for trend = 0.01), regardless of sex. The association with marine n-3 PUFAs was strongest among those with the shortest (≤5 years) duration of follow-up (HR = 1.49, 95% CI = 1.00–2.21, p for trend = 0.04). In contrast, we observed a small, albeit imprecise, inverse association with marine n-3 PUFAs for localized colorectal cancer among those with the longest duration of follow-up (>10 years) (HR = 0.62, 95% CI = 0.29–1.34, p for trend = 0.55). Our findings suggest that subtypes of fatty acids may differentially influence risk of colorectal cancer of a specified stage. PMID:18973226

  10. Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations.

    PubMed

    Fehringer, Gordon; Kraft, Peter; Pharoah, Paul D; Eeles, Rosalind A; Chatterjee, Nilanjan; Schumacher, Fredrick R; Schildkraut, Joellen M; Lindström, Sara; Brennan, Paul; Bickeböller, Heike; Houlston, Richard S; Landi, Maria Teresa; Caporaso, Neil; Risch, Angela; Amin Al Olama, Ali; Berndt, Sonja I; Giovannucci, Edward L; Grönberg, Henrik; Kote-Jarai, Zsofia; Ma, Jing; Muir, Kenneth; Stampfer, Meir J; Stevens, Victoria L; Wiklund, Fredrik; Willett, Walter C; Goode, Ellen L; Permuth, Jennifer B; Risch, Harvey A; Reid, Brett M; Bezieau, Stephane; Brenner, Hermann; Chan, Andrew T; Chang-Claude, Jenny; Hudson, Thomas J; Kocarnik, Jonathan K; Newcomb, Polly A; Schoen, Robert E; Slattery, Martha L; White, Emily; Adank, Muriel A; Ahsan, Habibul; Aittomäki, Kristiina; Baglietto, Laura; Blomquist, Carl; Canzian, Federico; Czene, Kamila; Dos-Santos-Silva, Isabel; Eliassen, A Heather; Figueroa, Jonine D; Flesch-Janys, Dieter; Fletcher, Olivia; Garcia-Closas, Montserrat; Gaudet, Mia M; Johnson, Nichola; Hall, Per; Hazra, Aditi; Hein, Rebecca; Hofman, Albert; Hopper, John L; Irwanto, Astrid; Johansson, Mattias; Kaaks, Rudolf; Kibriya, Muhammad G; Lichtner, Peter; Liu, Jianjun; Lund, Eiliv; Makalic, Enes; Meindl, Alfons; Müller-Myhsok, Bertram; Muranen, Taru A; Nevanlinna, Heli; Peeters, Petra H; Peto, Julian; Prentice, Ross L; Rahman, Nazneen; Sanchez, Maria Jose; Schmidt, Daniel F; Schmutzler, Rita K; Southey, Melissa C; Tamimi, Rulla; Travis, Ruth C; Turnbull, Clare; Uitterlinden, Andre G; Wang, Zhaoming; Whittemore, Alice S; Yang, Xiaohong R; Zheng, Wei; Buchanan, Daniel D; Casey, Graham; Conti, David V; Edlund, Christopher K; Gallinger, Steven; Haile, Robert W; Jenkins, Mark; Le Marchand, Loïc; Li, Li; Lindor, Noralene M; Schmit, Stephanie L; Thibodeau, Stephen N; Woods, Michael O; Rafnar, Thorunn; Gudmundsson, Julius; Stacey, Simon N; Stefansson, Kari; Sulem, Patrick; Chen, Y Ann; Tyrer, Jonathan P; Christiani, David C; Wei, Yongyue; Shen, Hongbing; Hu, Zhibin; Shu, Xiao-Ou; Shiraishi, Kouya; Takahashi, Atsushi; Bossé, Yohan; Obeidat, Ma'en; Nickle, David; Timens, Wim; Freedman, Matthew L; Li, Qiyuan; Seminara, Daniela; Chanock, Stephen J; Gong, Jian; Peters, Ulrike; Gruber, Stephen B; Amos, Christopher I; Sellers, Thomas A; Easton, Douglas F; Hunter, David J; Haiman, Christopher A; Henderson, Brian E; Hung, Rayjean J

    2016-09-01

    Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 controls) to identify pleiotropic loci. Findings were replicated in independent association studies (55,789 cases, 330,490 controls). We identified a novel pleiotropic association at 1q22 involving breast and lung squamous cell carcinoma, with eQTL analysis showing an association with ADAM15/THBS3 gene expression in lung. We also identified a known breast cancer locus CASP8/ALS2CR12 associated with prostate cancer, a known cancer locus at CDKN2B-AS1 with different variants associated with lung adenocarcinoma and prostate cancer, and confirmed the associations of a breast BRCA2 locus with lung and serous ovarian cancer. This is the largest study to date examining pleiotropy across multiple cancer-associated loci, identifying common mechanisms of cancer development and progression. Cancer Res; 76(17); 5103-14. ©2016 AACR.

  11. Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations.

    PubMed

    Fehringer, Gordon; Kraft, Peter; Pharoah, Paul D; Eeles, Rosalind A; Chatterjee, Nilanjan; Schumacher, Fredrick R; Schildkraut, Joellen M; Lindström, Sara; Brennan, Paul; Bickeböller, Heike; Houlston, Richard S; Landi, Maria Teresa; Caporaso, Neil; Risch, Angela; Amin Al Olama, Ali; Berndt, Sonja I; Giovannucci, Edward L; Grönberg, Henrik; Kote-Jarai, Zsofia; Ma, Jing; Muir, Kenneth; Stampfer, Meir J; Stevens, Victoria L; Wiklund, Fredrik; Willett, Walter C; Goode, Ellen L; Permuth, Jennifer B; Risch, Harvey A; Reid, Brett M; Bezieau, Stephane; Brenner, Hermann; Chan, Andrew T; Chang-Claude, Jenny; Hudson, Thomas J; Kocarnik, Jonathan K; Newcomb, Polly A; Schoen, Robert E; Slattery, Martha L; White, Emily; Adank, Muriel A; Ahsan, Habibul; Aittomäki, Kristiina; Baglietto, Laura; Blomquist, Carl; Canzian, Federico; Czene, Kamila; Dos-Santos-Silva, Isabel; Eliassen, A Heather; Figueroa, Jonine D; Flesch-Janys, Dieter; Fletcher, Olivia; Garcia-Closas, Montserrat; Gaudet, Mia M; Johnson, Nichola; Hall, Per; Hazra, Aditi; Hein, Rebecca; Hofman, Albert; Hopper, John L; Irwanto, Astrid; Johansson, Mattias; Kaaks, Rudolf; Kibriya, Muhammad G; Lichtner, Peter; Liu, Jianjun; Lund, Eiliv; Makalic, Enes; Meindl, Alfons; Müller-Myhsok, Bertram; Muranen, Taru A; Nevanlinna, Heli; Peeters, Petra H; Peto, Julian; Prentice, Ross L; Rahman, Nazneen; Sanchez, Maria Jose; Schmidt, Daniel F; Schmutzler, Rita K; Southey, Melissa C; Tamimi, Rulla; Travis, Ruth C; Turnbull, Clare; Uitterlinden, Andre G; Wang, Zhaoming; Whittemore, Alice S; Yang, Xiaohong R; Zheng, Wei; Buchanan, Daniel D; Casey, Graham; Conti, David V; Edlund, Christopher K; Gallinger, Steven; Haile, Robert W; Jenkins, Mark; Le Marchand, Loïc; Li, Li; Lindor, Noralene M; Schmit, Stephanie L; Thibodeau, Stephen N; Woods, Michael O; Rafnar, Thorunn; Gudmundsson, Julius; Stacey, Simon N; Stefansson, Kari; Sulem, Patrick; Chen, Y Ann; Tyrer, Jonathan P; Christiani, David C; Wei, Yongyue; Shen, Hongbing; Hu, Zhibin; Shu, Xiao-Ou; Shiraishi, Kouya; Takahashi, Atsushi; Bossé, Yohan; Obeidat, Ma'en; Nickle, David; Timens, Wim; Freedman, Matthew L; Li, Qiyuan; Seminara, Daniela; Chanock, Stephen J; Gong, Jian; Peters, Ulrike; Gruber, Stephen B; Amos, Christopher I; Sellers, Thomas A; Easton, Douglas F; Hunter, David J; Haiman, Christopher A; Henderson, Brian E; Hung, Rayjean J

    2016-09-01

    Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 controls) to identify pleiotropic loci. Findings were replicated in independent association studies (55,789 cases, 330,490 controls). We identified a novel pleiotropic association at 1q22 involving breast and lung squamous cell carcinoma, with eQTL analysis showing an association with ADAM15/THBS3 gene expression in lung. We also identified a known breast cancer locus CASP8/ALS2CR12 associated with prostate cancer, a known cancer locus at CDKN2B-AS1 with different variants associated with lung adenocarcinoma and prostate cancer, and confirmed the associations of a breast BRCA2 locus with lung and serous ovarian cancer. This is the largest study to date examining pleiotropy across multiple cancer-associated loci, identifying common mechanisms of cancer development and progression. Cancer Res; 76(17); 5103-14. ©2016 AACR. PMID:27197191

  12. Bioengineered Colorectal Cancer Drugs: Orally Delivered Anti-Inflammatory Agents.

    PubMed

    Urbanska, Aleksandra Malgorzata; Zhang, Xiaoying; Prakash, Satya

    2015-07-01

    Intestinal inflammation is one of the major factors that increase colorectal cancer (CRC) incidence worldwide. Inflammation in the gastrointestinal tract is directly linked to tumor development at the early stages of the disease, thus a key issue toward the prevention and the treatment of colonic neoplasia. Thus, the use of anti-inflammatory drugs has emerged first as a strategy to reduce chronic inflammation in case of many inflammatory bowel diseases (IBD), but it has proven its efficacy by reducing the risk of colonic neoplasia. This comprehensive review highlights the role of chronic inflammation, mainly in IBD, in the development of CRC including molecular and immune mechanisms that have tumorigenic effects. Multiple lines of evidence indicate that several bioactive and phytochemical compounds used as anti-inflammatory drugs have also antitumoral attributes. The uses of orally delivered cytokines and small molecules, as well as key dietary supplementation as anti-inflammatory therapeutics are discussed. In addition, comprehensive knowledge about CRC and intestinal inflammation, and the importance of the intestinal mucosal wall as a mucosal immunological barrier that comes into play during interactions with gut microbiota (pathogens and commensal), luminal secretions (bile acids, and bacterial and epithelial metabolites), and ingested chemicals (food components, high fat content, heterocyclic amines, and low intake of dietary fiber) are underscored. The multifunctionality of several anti-inflammatory drugs opens a line for their application in the treatment and prevention not only in IBD but also in CRC. Current bioengineering approaches for oral delivery of anti-inflammatory agents including cytokines, genetically modified bacteria, or small molecule inhibitors of inflammation directly contribute to the early management of CRC. Limitations of the current therapeutics, which stem from the lack of complete understanding of the complex molecular interactions

  13. The Association of Perceived Provider-Patient Communication and Relationship Quality with Colorectal Cancer Screening

    ERIC Educational Resources Information Center

    Underhill, Meghan L.; Kiviniemi, Marc T.

    2012-01-01

    Background: Two-thirds of adults aged 50 years and older are adherent to recommendations for colorectal cancer screening. Provider-patient communication and characteristics of the patient-provider relationship may relate to screening behavior. Methods: The association of provider communication quality, relationship, and colorectal cancer screening…

  14. Colorectal cancer in inflammatory bowel disease: results of the 3rd ECCO pathogenesis scientific workshop (I).

    PubMed

    Sebastian, Shaji; Hernández, Vincent; Myrelid, Pär; Kariv, Revital; Tsianos, Epameinondas; Toruner, Murat; Marti-Gallostra, Marc; Spinelli, Antonino; van der Meulen-de Jong, Andrea E; Yuksel, Elif Sarıtas; Gasche, Christoph; Ardizzone, Sandro; Danese, Silvio

    2014-01-01

    Epidemiological studies demonstrate an increased risk of colorectal cancer in patients with inflammatory bowel disease (IBD). A detailed literature review was conducted on epidemiology, risk factors, pathophysiology, chemoprevention and outcomes of colorectal cancer (CRC) in IBD as part of the 3rd ECCO scientific pathogenesis workshop.

  15. Prediagnostic plasma vitamin B6 (pyridoxal 50-phosphate) and survival in patients with colorectal cancer

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Higher plasma pyridoxal 5'-phosphate (PLP) levels are associated with a decreased incidence of colorectal cancer, but the influence of plasma PLP on survival of patients with colorectal cancer is unknown. We prospectively examined whether prediagnostic plasma PLP levels are associated with mortality...

  16. Public Awareness of Colorectal Cancer Screening: Knowledge, Attitudes, and Interventions for Increasing Screening Uptake

    PubMed Central

    Gimeno Garcia, Antonio Z.; Hernandez Alvarez Buylla, Noemi; Nicolas-Perez, David; Quintero, Enrique

    2014-01-01

    Colorectal cancer ranks as one of the most incidental and death malignancies worldwide. Colorectal cancer screening has proven its benefit in terms of incidence and mortality reduction in randomized controlled trials. In fact, it has been recommended by medical organizations either in average-risk or family-risk populations. Success of a screening campaign highly depends on how compliant the target population is. Several factors influence colorectal cancer screening uptake including sociodemographics, provider and healthcare system factors, and psychosocial factors. Awareness of the target population of colorectal cancer and screening is crucial in order to increase screening participation rates. Knowledge about this disease and its prevention has been used across studies as a measurement of public awareness. Some studies found a positive relationship between knowledge about colorectal cancer, risk perception, and attitudes (perceived benefits and barriers against screening) and willingness to participate in a colorectal cancer screening campaign. The mentioned factors are modifiable and therefore susceptible of intervention. In fact, interventional studies focused on average-risk population have tried to increase colorectal cancer screening uptake by improving public knowledge and modifying attitudes. In the present paper, we reviewed the factors impacting adherence to colorectal cancer screening and interventions targeting participants for increasing screening uptake. PMID:24729896

  17. DNA fingerprinting techniques for the analysis of genetic and epigenetic alterations in colorectal cancer.

    PubMed

    Samuelsson, Johanna K; Alonso, Sergio; Yamamoto, Fumiichiro; Perucho, Manuel

    2010-11-10

    Genetic somatic alterations are fundamental hallmarks of cancer. In addition to point and other small mutations targeting cancer genes, solid tumors often exhibit aneuploidy as well as multiple chromosomal rearrangements of large fragments of the genome. Whether somatic chromosomal alterations and aneuploidy are a driving force or a mere consequence of tumorigenesis remains controversial. Recently it became apparent that not only genetic but also epigenetic alterations play a major role in carcinogenesis. Epigenetic regulation mechanisms underlie the maintenance of cell identity crucial for development and differentiation. These epigenetic regulatory mechanisms have been found substantially altered during cancer development and progression. In this review, we discuss approaches designed to analyze genetic and epigenetic alterations in colorectal cancer, especially DNA fingerprinting approaches to detect changes in DNA copy number and methylation. DNA fingerprinting techniques, despite their modest throughput, played a pivotal role in significant discoveries in the molecular basis of colorectal cancer. The aim of this review is to revisit the fingerprinting technologies employed and the oncogenic processes that they unveiled.

  18. Guanylyl cyclase C in colorectal cancer: susceptibility gene and potential therapeutic target.

    PubMed

    Lin, Jieru E; Li, Peng; Pitari, Giovanni M; Schulz, Stephanie; Waldman, Scott A

    2009-05-01

    Colorectal cancer is one of the leading causes of tumor-related morbidity and mortality worldwide. While mechanisms underlying this disease have been elucidated over the past two decades, these molecular insights have failed to translate into efficacious therapy. The oncogenomic view of cancer suggests that terminal transformation reflects the sequential corruption of signal transduction circuits regulating key homeostatic mechanisms, whose multiplicity underlies the therapeutic resistance of most tumors to interventions targeting individual pathways. Conversely, the paucity of mechanistic insights into proximal pathophysiological processes that initiate and amplify oncogenic circuits preceding accumulation of mutations and transformation impedes development of effective prevention and therapy. In that context, guanylyl cyclase C (GCC), the intestinal receptor for the paracrine hormones guanylin and uroguanylin, whose early loss characterizes colorectal transformation, has emerged as a component of lineage-specific homeostatic programs organizing spatiotemporal patterning along the crypt-surface axis. Dysregulation of GCC signaling, reflecting hormone loss, promotes tumorigenesis through reprogramming of replicative and bioenergetic circuits and genomic instability. Compensatory upregulation of GCC in response to hormone loss provides a unique translational opportunity for prevention and treatment of colorectal tumors by hormone-replacement therapy.

  19. Applications of nanoparticles to diagnostics and therapeutics in colorectal cancer.

    PubMed

    Fortina, Paolo; Kricka, Larry J; Graves, David J; Park, Jason; Hyslop, Terry; Tam, Felicia; Halas, Naomi; Surrey, Saul; Waldman, Scott A

    2007-04-01

    Nanotechnology has considerable promise for the detection, staging and treatment of cancer. Here, we outline one such promising application: the use of nanostructures with surface-bound ligands for the targeted delivery and ablation of colorectal cancer (CRC), the third most common malignancy and the second most common cause of cancer-related mortality in the US. Normal colonic epithelial cells as well as primary CRC and metastatic tumors all express a unique surface-bound guanylyl cyclase C (GCC), which binds the diarrheagenic bacterial heat-stable peptide enterotoxin ST. This makes GCC a potential target for metastatic tumor ablation using ST-bound nanoparticles in combination with thermal ablation with near-infrared or radiofrequency energy absorption. Furthermore, the incorporation of iron or iron oxide into such structures would provide advantages for magnetic resonance imaging (MRI). Although the scenarios outlined in this article are hypothetical, they might stimulate ideas about how other cancers could be attacked using nanotechnology.

  20. Colorectal Cancer: Chemopreventive Role of Curcumin and Resveratrol

    PubMed Central

    Patel, Vaishali B.; Misra, Sabeena; Patel, Bhaumik B.; Majumdar, Adhip P. N.

    2013-01-01

    Colorectal cancer (CRC) is a second leading cause of cancer deaths in the Western world. Currently there is no effective treatment except resection at a very early stage with or with-out chemotherapy. Of various epithelial cancers, CRC in particular has a potential for prevention, since most cancers follow the adenoma-carcinoma sequence, and the interval between detection of an adenoma and its progression to carcinoma is usually about a decade. However no effective chemopreventive agent except COX-2 inhibitors, limited in their scope due to cardiovascular side effects, have shown promise in reducing adenoma recurrence. To this end, natural agents that can target important carcinogenic pathways without demonstrating discernible adverse effects would serve as ideal chemoprevention agents. In this review, we discuss merits of two such naturally occurring dietary agents—curcumin and resveratrol—for chemoprevention of CRC. PMID:20924971

  1. Results of Colorectal Cancer Screening of the National Cancer Screening Program in Korea, 2008

    PubMed Central

    Shim, Jung Im; Han, Mi Ah; Lee, Hoo-Yeon; Choi, Kui Sun; Jun, Jae Kwan; Park, Eun-Cheol

    2010-01-01

    Purpose This study aims to investigate the current situation of national colorectal cancer screening by analyzing participation rates, positive rates of screening methods and screening rate of secondary screening tests in colorectal screening of the national cancer screening program in 2008. Materials and Methods With database about target population and screened individuals of the national cancer screening program, the results of target population and participants of colorectal cancer screening in 2008 were analyzed. Among adults aged over 50 years of medical aid and beneficiaries of national health insurance paying lower 50% premiums in the total subscribers, 4,640,365 were target population of colorectal cancer screening and the data of 984,915 undergoing fecal occult blood test (FOBT) as a primary screening were analyzed. Results The colorectal cancer screening rate was 21.2% and the rates of national health insurance subscribers, females and the elderly aged 60-64 years were higher than those of others. The recipients with a positive result in FOBT recorded approximately 7.5%. Medical aid beneficiaries (7.9%), males (8.8%) and seniors aged over 75 years (9.1%) showed higher positive rates than the average one. Out of the FOBT positive recipients, 43.0% took a secondary screening and the rate undergoing colonoscopy (31.4%) was higher than that of doing double-contrast barium enema test (11.6%). Conclusion Colorectal cancer screening rate of medical aid beneficiaries and people paying lower 50% premiums among national health insurance subscribers, was different according to demographic characters (gender, age and types of health insurance). This finding meant that screening for the vulnerable needed to be encouraged by considering socio-demographic characters. Additionally, more efforts were necessary to increase the secondary screening rate of people with a positive result in primary one. PMID:21253320

  2. LEP gene variant is associated with prostate cancer but not with colorectal cancer.

    PubMed

    He, Juan; Xu, Guili

    2013-10-01

    The leptin (LEP) gene has been considered to be implicated in the development of cancer. However, the results have been inconsistent. In this study, we performed a meta-analysis to clarify the association of LEP rs7799039 variant with colorectal and prostate cancer risk. Published literatures from PubMed and Embase were retrieved. Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated using fixed or random effects model. A total of five studies (2,596 colorectal cancer cases and 3,240 controls) for association of LEP rs7799039 variant with colorectal cancer, and three studies (1,343 prostate cancer cases and 1,238 controls) for association with prostate cancer were included in the meta-analysis. For colorectal cancer, there was no significant association of LEP rs7799039 variant with this disease under homogeneous co-dominant model (OR = 0.88, 95 % CI = 0.75-1.02), heterogeneous co-dominant model (OR = 1.00, 95 % CI = 0.89-1.13) and dominant model (OR = 0.97, 95 % CI = 0.87-1.08); however, there was a marginal association under recessive model (OR = 0.87, 95 % CI = 0.76-0.99). For prostate cancer, there was significant association of LEP rs7799039 variant with this disease under homogeneous co-dominant model (OR = 1.33, 95 % CI = 1.06-1.67) and recessive model (OR = 1.26, 95 % CI = 1.05-1.51), but not under heterogeneous co-dominant model (OR = 1.24, 95 % CI = 0.87-1.77) and dominant model (OR = 1.30, 95 % CI = 1.84). The present meta-analysis demonstrated that the LEP rs7799039 variant was associated with prostate cancer, but not with colorectal cancer.

  3. Human papillomavirus detection in paraffin-embedded colorectal cancer tissues.

    PubMed

    Tanzi, Elisabetta; Bianchi, Silvia; Frati, Elena R; Amicizia, Daniela; Martinelli, Marianna; Bragazzi, Nicola L; Brisigotti, Maria Pia; Colzani, Daniela; Fasoli, Ester; Zehender, Gianguglielmo; Panatto, Donatella; Gasparini, Roberto

    2015-01-01

    Human papillomavirus (HPV) has a well-recognized aetiological role in the development of cervical cancer and other anogenital tumours. Recently, an association between colorectal cancer and HPV infection has been suggested, although this is still controversial. This study aimed at detecting and characterizing HPV infection in 57 paired biopsies from colorectal cancers and adjacent intact tissues using a degenerate PCR approach. All amplified fragments were genotyped by means of sequencing. Overall, HPV prevalence was 12.3 %. In particular, 15.8 % of tumour tissues and 8.8 % of non-cancerous tissue samples were HPV DNA-positive. Of these samples, 85.7 % were genotyped successfully, with 41.7 % of sequences identifying four genotypes of the HR (high oncogenic risk) clade Group 1; the remaining 58.3 % of HPV-genotyped specimens had an unclassified β-HPV. Examining additional cases and analysing whole genomes will help to outline the significance of these findings.

  4. Genetics, diagnosis and management of colorectal cancer (Review)

    PubMed Central

    DE ROSA, MARINA; PACE, UGO; REGA, DANIELA; COSTABILE, VALERIA; DURATURO, FRANCESCA; IZZO, PAOLA; DELRIO, PAOLO

    2015-01-01

    Colorectal cancer (CRC) is the third most common type of cancer worldwide and a leading cause of cancer death. Surgery represents the mainstay of treatment in early cases but often patients are primarily diagnosed in an advanced stage of disease and sometimes also distant metastases are present. Neoadjuvant therapy is therefore needed but drug resistance may influence response and concur to recurrent disease. At molecular level, it is a very heterogeneous group of diseases with about 30% of hereditary or familial cases. During colorectal adenocarcinomas development, epithelial cells from gastrointestinal trait acquire sequential genetic and epigenetic mutations in specific oncogenes and/or tumour suppressor genes, causing CRC onset, progression and metastasis. Molecular characterization of cancer associated mutations gives valuable information about disease prognosis and response to the therapy. Very early diagnosis and personalized care, as well as a better knowledge of molecular basis of its onset and progression, are therefore crucial to obtain a cure of CRC. In this review, we describe updated genetics, current diagnosis and management of CRC pointing out the extreme need for a multidisciplinary approach to achieve the best results in patient outcomes. PMID:26151224

  5. The emerging role of immunotherapy in colorectal cancer.

    PubMed

    Lynch, David; Murphy, Adrian

    2016-08-01

    Modulation of the interaction between the immune system and the tumor microenvironment has long been a target of cancer research, including colorectal cancer (CRC). Approaches explored to date include vaccines (autologous, peptide, dendritic cell, viral and bacterial), cytokine therapy, toll-like receptors (TLRs), autologous cell therapy and checkpoint inhibition. Until recently these approaches have been shown to have only modest efficacy in reducing tumor burden. However, significant breakthroughs have been made, with the use of checkpoint inhibitors targeting programmed cell death protein-1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T lymphocyte antigen-4 (CTLA-4). Immunotherapy now represents a possible avenue of curative treatment for those with chemo-otherwise refractory tumors. Success with this approach to immunotherapy has largely been confined to tumors with high mutational burdens such as melanoma, renal cell carcinoma (RCC) and non-small cell lung cancer. This observation led to the exploration and successful use of checkpoint inhibitors in those with mismatch repair colorectal cancer which have a relatively high mutational burden. Ongoing trials are focused on further exploring the use of checkpoint inhibitors in addition to investigating the various combinations of immunotherapeutic drugs. PMID:27668225

  6. New NSAID Targets and Derivatives for Colorectal Cancer Chemoprevention

    PubMed Central

    Tinsley, Heather N.; Grizzle, William E.; Abadi, Ashraf; Keeton, Adam; Zhu, Bing; Xi, Yaguang

    2013-01-01

    Clinical and preclinical studies provide strong evidence that nonsteroidal anti-inflammatory drugs (NSAIDs) can prevent numerous types of cancers, especially colorectal cancer. Unfortunately, the depletion of physiologically important prostaglandins due to cyclooxygenase (COX) inhibition results in potentially fatal toxicities that preclude the long-term use of NSAIDs for cancer chemoprevention. While studies have shown an involvement of COX-2 in colorectal tumorigenesis, other studies suggest that a COX-independent target may be at least partially responsible for the antineoplastic activity of NSAIDs. For example, certain NSAID derivatives have been identified that do not inhibit COX-2 but have demonstrated efficacy to suppress carcinogenesis with potential for reduced toxicity. A number of alternative targets have also been reported to account for the tumor cell growth inhibitory activity of NSAIDs, including the inhibition of cyclic guanosine monophosphate phosphodiesterases (cGMP PDEs), generation of reactive oxygen species (ROS), the suppression of the apoptosis inhibitor protein, survivin, and others. Here, we review several promising mechanisms that are being targeted to develop safer and more efficacious NSAID derivatives for colon cancer chemoprevention. PMID:22893202

  7. Colorectal cancer tumour markers and biomarkers: Recent therapeutic advances

    PubMed Central

    Lech, Gustaw; Słotwiński, Robert; Słodkowski, Maciej; Krasnodębski, Ireneusz Wojciech

    2016-01-01

    Colorectal cancer (CRC) is the second most commonly diagnosed cancer among females and third among males worldwide. It also contributes significantly to cancer-related deaths, despite the continuous progress in diagnostic and therapeutic methods. Biomarkers currently play an important role in the detection and treatment of patients with colorectal cancer. Risk stratification for screening might be augmented by finding new biomarkers which alone or as a complement of existing tests might recognize either the predisposition or early stage of the disease. Biomarkers have also the potential to change diagnostic and treatment algorithms by selecting the proper chemotherapeutic drugs across a broad spectrum of patients. There are attempts to personalise chemotherapy based on presence or absence of specific biomarkers. In this review, we update review published last year and describe our understanding of tumour markers and biomarkers role in CRC screening, diagnosis, treatment and follow-up. Goal of future research is to identify those biomarkers that could allow a non-invasive and cost-effective diagnosis, as well as to recognise the best prognostic panel and define the predictive biomarkers for available treatments. PMID:26855534

  8. The emerging role of immunotherapy in colorectal cancer

    PubMed Central

    Lynch, David

    2016-01-01

    Modulation of the interaction between the immune system and the tumor microenvironment has long been a target of cancer research, including colorectal cancer (CRC). Approaches explored to date include vaccines (autologous, peptide, dendritic cell, viral and bacterial), cytokine therapy, toll-like receptors (TLRs), autologous cell therapy and checkpoint inhibition. Until recently these approaches have been shown to have only modest efficacy in reducing tumor burden. However, significant breakthroughs have been made, with the use of checkpoint inhibitors targeting programmed cell death protein-1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T lymphocyte antigen-4 (CTLA-4). Immunotherapy now represents a possible avenue of curative treatment for those with chemo-otherwise refractory tumors. Success with this approach to immunotherapy has largely been confined to tumors with high mutational burdens such as melanoma, renal cell carcinoma (RCC) and non-small cell lung cancer. This observation led to the exploration and successful use of checkpoint inhibitors in those with mismatch repair colorectal cancer which have a relatively high mutational burden. Ongoing trials are focused on further exploring the use of checkpoint inhibitors in addition to investigating the various combinations of immunotherapeutic drugs.

  9. The emerging role of immunotherapy in colorectal cancer

    PubMed Central

    Lynch, David

    2016-01-01

    Modulation of the interaction between the immune system and the tumor microenvironment has long been a target of cancer research, including colorectal cancer (CRC). Approaches explored to date include vaccines (autologous, peptide, dendritic cell, viral and bacterial), cytokine therapy, toll-like receptors (TLRs), autologous cell therapy and checkpoint inhibition. Until recently these approaches have been shown to have only modest efficacy in reducing tumor burden. However, significant breakthroughs have been made, with the use of checkpoint inhibitors targeting programmed cell death protein-1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T lymphocyte antigen-4 (CTLA-4). Immunotherapy now represents a possible avenue of curative treatment for those with chemo-otherwise refractory tumors. Success with this approach to immunotherapy has largely been confined to tumors with high mutational burdens such as melanoma, renal cell carcinoma (RCC) and non-small cell lung cancer. This observation led to the exploration and successful use of checkpoint inhibitors in those with mismatch repair colorectal cancer which have a relatively high mutational burden. Ongoing trials are focused on further exploring the use of checkpoint inhibitors in addition to investigating the various combinations of immunotherapeutic drugs. PMID:27668225

  10. Germline Mutations in FAN1 Cause Hereditary Colorectal Cancer by Impairing DNA Repair.

    PubMed

    Seguí, Nuria; Mina, Leonardo B; Lázaro, Conxi; Sanz-Pamplona, Rebeca; Pons, Tirso; Navarro, Matilde; Bellido, Fernando; López-Doriga, Adriana; Valdés-Mas, Rafael; Pineda, Marta; Guinó, Elisabet; Vidal, August; Soto, José Luís; Caldés, Trinidad; Durán, Mercedes; Urioste, Miguel; Rueda, Daniel; Brunet, Joan; Balbín, Milagros; Blay, Pilar; Iglesias, Silvia; Garré, Pilar; Lastra, Enrique; Sánchez-Heras, Ana Beatriz; Valencia, Alfonso; Moreno, Victor; Pujana, Miguel Ángel; Villanueva, Alberto; Blanco, Ignacio; Capellá, Gabriel; Surrallés, Jordi; Puente, Xose S; Valle, Laura

    2015-09-01

    Identification of genes associated with hereditary cancers facilitates management of patients with family histories of cancer. We performed exome sequencing of DNA from 3 individuals from a family with colorectal cancer who met the Amsterdam criteria for risk of hereditary nonpolyposis colorectal cancer. These individuals had mismatch repair-proficient tumors and each carried nonsense variant in the FANCD2/FANCI-associated nuclease 1 gene (FAN1), which encodes a nuclease involved in DNA inter-strand cross-link repair. We sequenced FAN1 in 176 additional families with histories of colorectal cancer and performed in vitro functional analyses of the mutant forms of FAN1 identified. We detected FAN1 mutations in approximately 3% of families who met the Amsterdam criteria and had mismatch repair-proficient cancers with no previously associated mutations. These findings link colorectal cancer predisposition to the Fanconi anemia DNA repair pathway, supporting the connection between genome integrity and cancer risk.

  11. Folic acid and sodium butyrate prevent tumorigenesis in a mouse model of colorectal cancer.

    PubMed

    Lu, Rong; Wang, Xia; Sun, Dan-Feng; Tian, Xiao-Qing; Zhao, Shu-Liang; Chen, Ying-Xuan; Fang, Jing-Yuan

    2008-11-01

    Colorectal cancer is a leading cause of morbidity and mortality worldwide, and its incidence has been increasing in recent years. The role of epigenetic modifications, including DNA methylation and histone modifications, has only recently been investigated. In this study, the effects of epigenetic agents such as folic acid (FA) and sodium butyrate (NaBu) on the development of colorectal cancer induced by 1,2-dimethylhydrazine (DMH) using ICR mice was examined. Of the mice treated in a chemopreventive manner with epigenetic agents, FA and NaBu, 15-50% developed colorectal cancer at 24 weeks compared with a 95% incidence of colorectal cancer in DMH-treated control mice. Folate deficiency can alter cytosine methylation in DNA leading to inappropriate activation of the proto-oncogene c-myc. We detected lower levels of p21(WAF1) gene expression in colorectal cancer samples, as well as significantly lower levels of acetylated histone H3, compared with samples from corresponding normal colorectal mucosa. In contrast, administration of NaBu increased levels of p21(WAF1) mRNA and p21(WAF1) protein, and was associated with an accumulation of histone acetylation. In summary, our results show that FA and NaBu reduce the incidence of colorectal cancer induced by DMH-induced in ICR mice, and therefore we hypothesize that targeting epigenetic targets should be further investigated for the prevention of colorectal cancer in humans.

  12. Long-term disease-free survival after surgical resection for multiple bone metastases from rectal cancer

    PubMed Central

    Choi, Seok Jin; Kim, Jong Hun; Lee, Min Ro; Lee, Chang Ho; Kuh, Ja Hong; Kim, Jung Ryul

    2011-01-01

    Bone metastasis of primary colorectal cancer is uncommon. When it occurs, it is usually a late manifestation of disease and is indicative of poor prognosis. We describe a patient with multiple metachronous bone metastases from lower rectal cancer who was successfully treated with multimodal treatment including surgical resections and has shown 32 mo disease-free survival. Surgical resection of metastatic bone lesion(s) from colorectal cancer may be a good treatment option in selected patients. PMID:21876853

  13. Meat intake, cooking methods, dietary carcinogens, and colorectal cancer risk: findings from the Colorectal Cancer Family Registry

    PubMed Central

    Joshi, Amit D; Kim, Andre; Lewinger, Juan Pablo; Ulrich, Cornelia M; Potter, John D; Cotterchio, Michelle; Le Marchand, Loic; Stern, Mariana C

    2015-01-01

    Diets high in red meat and processed meats are established colorectal cancer (CRC) risk factors. However, it is still not well understood what explains this association. We conducted comprehensive analyses of CRC risk and red meat and poultry intakes, taking into account cooking methods, level of doneness, estimated intakes of heterocyclic amines (HCAs) that accumulate during meat cooking, tumor location, and tumor mismatch repair proficiency (MMR) status. We analyzed food frequency and portion size data including a meat cooking module for 3364 CRC cases, 1806 unaffected siblings, 136 unaffected spouses, and 1620 unaffected population-based controls, recruited into the CRC Family Registry. Odds ratios (OR) and 95% confidence intervals (CI) for nutrient density variables were estimated using generalized estimating equations. We found no evidence of an association between total nonprocessed red meat or total processed meat and CRC risk. Our main finding was a positive association with CRC for pan-fried beefsteak (Ptrend < 0.001), which was stronger among MMR deficient cases (heterogeneity P = 0.059). Other worth noting associations, of borderline statistical significance after multiple testing correction, were a positive association between diets high in oven-broiled short ribs or spareribs and CRC risk (Ptrend = 0.002), which was also stronger among MMR-deficient cases, and an inverse association with grilled hamburgers (Ptrend = 0.002). Our results support the role of specific meat types and cooking practices as possible sources of human carcinogens relevant for CRC risk. PMID:25846122

  14. Oral manifestations of hereditary nonpolyposis colorectal cancer syndrome: a family case series

    PubMed Central

    2014-01-01

    Introduction Hereditary nonpolyposis colorectal cancer is a colorectal cancer syndrome characterized by the development of colorectal cancer and extracolonic tumors, and this syndrome has an autosomal dominant mode of inheritance. To our knowledge, our study was the first to find dento-osseous anomalies and the second to observe Fordyce granules in a family with individuals with hereditary nonpolyposis colorectal cancer. Case presentations Twenty members of one Brazilian family with individuals with hereditary nonpolyposis colorectal cancer were analyzed according to the presence of colorectal cancer and the occurrence of Fordyce granules and dento-osseous anomalies. Their average age was 29.6 (range 7 to 53 years) years. Medical examinations of this family with hereditary nonpolyposis colorectal cancer were performed at the Coloproctology Division of our hospital. Then, all individuals were referred to our Oral Care Center for Inherited Diseases for intraoral examinations to verify the presence of Fordyce granules. Dental panoramic radiographs were done in order to describe dento-osseous anomalies on applying the Dental Panoramic Radiograph System. Of the 20 family members, four were diagnosed with hereditary nonpolyposis colorectal cancer and all four presented Fordyce granules in their upper lip, but only one of these four patients (Case 2) had a significant dento-osseous anomaly. Conclusions Our familial study verified the presence of Fordyce granules in all individuals diagnosed with hereditary nonpolyposis colorectal cancer, and the presence of significant dento-osseous anomalies in one of these cases. However, the relationship between oral manifestations and hereditary nonpolyposis colorectal cancer should be further investigated. PMID:25012300

  15. Update in Cancer Chemotherapy: Gastrointestinal Cancer—Colorectal Cancer, Part 2

    PubMed Central

    Wright, Jane C.

    1986-01-01

    An update of the state of the art of cancer chemotherapeutic treatment of gastrointestinal tract cancer is described in a multi-part series. Part 1 surveyed colorectal cancer and the use of single-agent chemotherapy in the April issue of the Journal. Part 2 of colorectal cancer will describe combination chemotherapy, preoperative and postoperative radiation, and combinations of chemotherapy and radiation, and adjuvant chemotherapy. In advanced gastrointestinal tract cancer, chemotherapy is only of palliative value with response rates generally under 50 percent and survival rates of several months to one year or more. Combination chemotherapy often produces higher response rates, yet there is no acceptable evidence that survival is improved. While some adjuvant chemotherapy trials suggest improvement, major survival gains remain to be demonstrated. Uncertainty as to the role of chemotherapy in the treatment of gastrointestinal cancers may be due to lack of data. PMID:3519988

  16. Family history of cancer, body weight, and p53 nuclear overexpression in Duke's C colorectal cancer.

    PubMed Central

    Zhang, Z. F.; Zeng, Z. S.; Sarkis, A. S.; Klimstra, D. S.; Charytonowicz, E.; Pollack, D.; Vena, J.; Guillem, J.; Marshall, J. R.; Cordon-Cardo, C.

    1995-01-01

    To examine the hypothesis that colorectal carcinomas with and without TP53 mutations may be characterised by aetiological heterogeneity, we analysed a group of 107 patients with primary Dukes' C colorectal cancer seen at the Memorial Sloan-Kettering Cancer Center (MSKCC) from 1986 to 1990. We assessed p53 overexpression using the monoclonal antibody PAb 1801, and identified 42 (39%) patients displaying p53-positive phenotype, defined as > or = 25% of positive cells. Patients with two or more first-degree relatives with cancer had an odds ratio (OR) of 2.9 (95% CI 1.0-8.3) for p53 overexpression in comparison with those without a family history of cancer (trend test, P = 0.11). A possible association between body weight and p53 overexpression was observed. The ORs were 1.9 for the second quartile, 1.9 for the third quartile and 3.4 for the highest quartile in comparison with the lowest quartile (trend test, P = 0.06). No association between occupational physical activity, smoking, drinking, parity and p53 overexpression was identified. The results suggest that p53 overexpression may be related to genetic predisposition to colorectal cancer, and p53-positive and p53-negative colorectal cancers may be controlled by different aetiological pathways. Images Figure 1 PMID:7710960

  17. Does ethnicity affect survival following colorectal cancer? A prospective, cohort study using Iranian cancer registry

    PubMed Central

    Ahmadi, Ali; Hashemi Nazari, Seyed Saeed; Mobasheri, Mahmoud

    2014-01-01

    Background: The present study compared the differences between survivals of patients with colorectal cancer according to their ethnicity adjusted for other predictors of survival. Methods: In this prospective cohort study patients were followed up from definite diagnosis of colorectal cancer to death. Totally, 2431 person-year follow-ups were undertaken for 1127 colorectal cancer patients once every six months. The data were analyzed by stata software using bivariate analysis, multivariate analysis, and Cox regression. Results: The age at diagnosis was significantly different between men and women (p<0.03). 61.2% were male and the rest were female. Most patients were Fars (51.2%), followed by Turciks (21.5%), Kurds (8.2%), and 7.5% Lurs. Of the patients, 75% had a survival of more than 2.72 years, 50% a survival of 5.83 years, and 25% longer than 13.1 years after diagnosis. Risk ratio was significantly different among ethnics (p<0.05). The variables of ethnicity, being non married, tumor grade, family history of cancer, and smoking were considered as determinants of the patients’ survival in Cox regression model. The median survival time in Fars, Kurds, Lurs, Turks and other ethnics was 5.83, 2.44, 5.49, and 8.52 years, respectively. Conclusion: Ethnicity and access to healthcare are predictors of survival of patients with colorectal cancer which may define priorities in controlling cancer and implementing interventional and prevention plans. PMID:25664284

  18. Colorectal Cancer Epidemiology in the Nurses’ Health Study

    PubMed Central

    Lee, Dong Hoon; Giovannucci, Edward L.

    2016-01-01

    Objectives. To review the contribution of the Nurses’ Health Study (NHS) to identifying risk and protective factors for colorectal adenomas and colorectal cancer (CRC). Methods. We performed a narrative review of the publications using the NHS between 1976 and 2016. Results. Existing epidemiological studies using the NHS have reported that red and processed meat, alcohol, smoking, and obesity were associated with an increased risk of CRC, whereas folate, calcium, vitamin D, aspirin, and physical activity were associated with decreased risk of CRC. Moreover, modifiable factors, such as physical activity, vitamin D, folate, insulin and insulin-like growth factor binding protein-1, and diet quality, were identified to be associated with survival among CRC patients. In recent years, molecular pathological epidemiological studies have been actively conducted and have shown refined results by molecular subtypes of CRC. Conclusions. The NHS has provided new insights into colorectal adenomas, CRC etiology, and pathogenic mechanisms. With its unique strengths, the NHS should continue to contribute to the field of CRC epidemiology and play a major role in public health. PMID:27459444

  19. REACTIVE OXYGEN SPECIES AND COLORECTAL CANCER

    PubMed Central

    Sreevalsan, Sandeep; Safe, Stephen

    2013-01-01

    Several agents used for treatment of colon and other cancers induce reactive oxygen species (ROS) and this plays an important role in their anticancer activities. In addition to the well-known proapoptotic effects of ROS inducers, these compounds also decrease expression of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 and several pro-oncogenic Spregulated genes important for cancer cell proliferation, survival and metastasis. The mechanism of these responses involve ROS-dependent downregulation of microRNA-27a (miR-27a) or miR-20a (and paralogs) and induction of two Sp-repressors, ZBTB10 and ZBTB4 respectively. This pathway significantly contributes to the anticancer activity of ROS inducers and should be considered in development of drug combinations for cancer chemotherapy. PMID:25584043

  20. Accumulation of arachidonic acid-containing phosphatidylinositol at the outer edge of colorectal cancer

    PubMed Central

    Hiraide, Takanori; Ikegami, Koji; Sakaguchi, Takanori; Morita, Yoshifumi; Hayasaka, Takahiro; Masaki, Noritaka; Waki, Michihiko; Sugiyama, Eiji; Shinriki, Satoru; Takeda, Makoto; Shibasaki, Yasushi; Miyazaki, Shinichiro; Kikuchi, Hirotoshi; Okuyama, Hiroaki; Inoue, Masahiro; Setou, Mitsutoshi; Konno, Hiroyuki

    2016-01-01

    Accumulating evidence indicates that cancer cells show specific alterations in phospholipid metabolism that contribute to tumour progression in several types of cancer, including colorectal cancer. Questions still remain as to what lipids characterize the outer edge of cancer tissues and whether those cancer outer edge-specific lipid compositions emerge autonomously in cancer cells. Cancer tissue-originated spheroids (CTOSs) that are composed of pure primary cancer cells have been developed. In this study, we aimed to seek out the cancer cell-autonomous acquisition of cancer outer edge-characterizing lipids in colorectal cancer by analysing phospholipids in CTOSs derived from colorectal cancer patients with matrix-assisted laser desorption/ionization (MALDI)-imaging mass spectrometry (IMS). A signal at m/z 885.5 in negative ion mode was detected specifically at the surface regions. The signal was identified as an arachidonic acid (AA)-containing phosphatidylinositol (PI), PI(18:0/20:4), by tandem mass spectrometry analysis. Quantitative analysis revealed that the amount of PI(18:0/20:4) in the surface region of CTOSs was two-fold higher than that in the medial region. Finally, PI(18:0/20:4) was enriched at the cancer cells/stromal interface in colorectal cancer patients. These data imply a possible importance of AA-containing PI for colorectal cancer progression, and suggest cells expressing AA-containing PI as potential targets for anti-cancer therapy. PMID:27435310

  1. The Source and Credibility of Colorectal Cancer Information on Twitter.

    PubMed

    Park, SoHyun; Oh, Heung-Kwon; Park, Gibeom; Suh, Bongwon; Bae, Woo Kyung; Kim, Jin Won; Yoon, Hyuk; Kim, Duck-Woo; Kang, Sung-Bum

    2016-02-01

    Despite the rapid penetration of social media in modern life, there has been limited research conducted on whether social media serves as a credible source of health information. In this study, we propose to identify colorectal cancer information on Twitter and assess its informational credibility. We collected Twitter messages containing colorectal cancer-related keywords, over a 3-month period. A review of sample tweets yielded content and user categorization schemes. The results of the sample analysis were applied to classify all collected tweets and users, using a machine learning technique. The credibility of the information in the sampled tweets was evaluated. A total of 76,119 tweets were analyzed. Individual users authored the majority of tweets (n = 68,982, 90.6%). They mostly tweeted about news articles/research (n = 16,761, 22.0%) and risk/prevention (n = 14,767, 19.4%). Medical professional users generated only 2.0% of total tweets (n = 1509), and medical institutions rarely tweeted (n = 417, 0.6%). Organizations tended to tweet more about information than did individuals (85.2% vs 63.1%; P < 0.001). Credibility analysis of medically relevant sample tweets revealed that most were medically correct (n = 1763, 84.5%). Among those, more frequently retweeted tweets contained more medically correct information than randomly selected tweets (90.7% vs 83.2%; P < 0.01). Our results demonstrate an interest in and an engagement with colorectal cancer information from a large number and variety of users. Coupled with the Internet's potential to increase social support, Twitter may contribute to enhancing public health and empowering users, when used with proper caution. PMID:26886625

  2. The impact of new technology on surgery for colorectal cancer

    PubMed Central

    Makin, Gregory B; Breen, David J; Monson, John RT

    2001-01-01

    Advances in technology continue at a rapid pace and affect all aspects of life, including surgery. We have reviewed some of these advances and the impact they are having on the investigation and management of colorectal cancer. Modern endoscopes, with magnifying, variable stiffness and localisation capabilities are making the primary investigation of colonic cancer easier and more acceptable for patients. Imaging investigations looking at primary, metastatic and recurrent disease are shifting to digital data sets, which can be stored, reviewed remotely, potentially fused with other modalities and reconstructed as 3 dimensional (3D) images for the purposes of advanced diagnostic interpretation and computer assisted surgery. They include virtual colonoscopy, trans-rectal ultrasound, magnetic resonance imaging, positron emission tomography and radioimmunoscintigraphy. Once a colorectal carcinoma is diagnosed, the treatment options available are expanding. Colonic stents are being used to relieve large bowel obstruction, either as a palliative measure or to improve the patient’s overall condition before definitive surgery. Transanal endoscopic microsurgery and minimally invasive techniques are being used with similar outcomes and a lower mortality, morbidity and hospital stay than open trans-abdominal surgery. Transanal endoscopic microsurgery allows precise excision of both benign and early malignant lesions in the mid and upper rectum. Survival of patients with inoperable hepatic metastases following radiofrequency ablation is encouraging. Robotics and telemedicine are taking surgery well into the 21st century. Artificial neural networks are being developed to enable us to predict the outcome for individual patients. New technology has a major impact on the way we practice surgery for colorectal cancer. PMID:11819841

  3. The Source and Credibility of Colorectal Cancer Information on Twitter

    PubMed Central

    Park, SoHyun; Oh, Heung-Kwon; Park, Gibeom; Suh, Bongwon; Bae, Woo Kyung; Kim, Jin Won; Yoon, Hyuk; Kim, Duck-Woo; Kang, Sung-Bum

    2016-01-01

    Abstract Despite the rapid penetration of social media in modern life, there has been limited research conducted on whether social media serves as a credible source of health information. In this study, we propose to identify colorectal cancer information on Twitter and assess its informational credibility. We collected Twitter messages containing colorectal cancer-related keywords, over a 3-month period. A review of sample tweets yielded content and user categorization schemes. The results of the sample analysis were applied to classify all collected tweets and users, using a machine learning technique. The credibility of the information in the sampled tweets was evaluated. A total of 76,119 tweets were analyzed. Individual users authored the majority of tweets (n = 68,982, 90.6%). They mostly tweeted about news articles/research (n = 16,761, 22.0%) and risk/prevention (n = 14,767, 19.4%). Medical professional users generated only 2.0% of total tweets (n = 1509), and medical institutions rarely tweeted (n = 417, 0.6%). Organizations tended to tweet more about information than did individuals (85.2% vs 63.1%; P < 0.001). Credibility analysis of medically relevant sample tweets revealed that most were medically correct (n = 1763, 84.5%). Among those, more frequently retweeted tweets contained more medically correct information than randomly selected tweets (90.7% vs 83.2%; P < 0.01). Our results demonstrate an interest in and an engagement with colorectal cancer information from a large number and variety of users. Coupled with the Internet's potential to increase social support, Twitter may contribute to enhancing public health and empowering users, when used with proper caution. PMID:26886625

  4. Impact of proteolytic enzymes in colorectal cancer development and progression

    PubMed Central

    Herszényi, László; Barabás, Loránd; Hritz, István; István, Gábor; Tulassay, Zsolt

    2014-01-01

    Tumor invasion and metastasis is a highly complicated, multi-step phenomenon. In the complex event of tumor progression, tumor cells interact with basement membrane and extracellular matrix components. Proteolytic enzymes (proteinases) are involved in the degradation of extracellular matrix, but also in cancer invasion and metastasis. The four categories of proteinases (cysteine-, serine-, aspartic-, and metalloproteinases) are named and classified according to the essential catalytic component in their active site. We and others have shown that proteolytic enzymes play a major role not only in colorectal cancer (CRC) invasion and metastasis, but also in malignant transformation of precancerous lesions into cancer. Tissue and serum-plasma antigen concentrations of proteinases might be of great value in identifying patients with poor prognosis in CRC. Our results, in concordance with others indicate the potential tumor marker impact of proteinases for the early diagnosis of CRC. In addition, proteinases may also serve as potential target molecules for therapeutic agents. PMID:25309062

  5. Mass Spectrometry-Based N-Glycomics of Colorectal Cancer

    PubMed Central

    Sethi, Manveen K.; Fanayan, Susan

    2015-01-01

    Colorectal cancer (CRC) is one of the most prevalent cancers worldwide. An increased molecular understanding of the CRC pathology is warranted to gain insights into the underlying molecular and cellular mechanisms of the disease. Altered protein glycosylation patterns are associated with most diseases including malignant transformation. Recent advances in mass spectrometry and bioinformatics have accelerated glycomics research and present a new paradigm for cancer biomarker discovery. Mass spectrometry (MS)-based glycoproteomics and glycomics, therefore, hold considerable promise to improve the discovery of novel biomarkers with utility in disease diagnosis and therapy. This review focuses on the emerging field of glycomics to present a comprehensive review of advances in technologies and their application in studies aimed at discovering novel glycan-based biomarkers. We will also discuss some of the challenges associated with using glycans as biomarkers. PMID:26690136

  6. Stem vs non-stem cell origin of colorectal cancer

    PubMed Central

    Huels, D J; Sansom, O J

    2015-01-01

    Colorectal cancer (CRC) is one of the most common cancers in the western world and is characterised by deregulation of the Wnt signalling pathway. Mutation of the adenomatous polyposis coli (APC) tumour suppressor gene, which encodes a protein that negatively regulates this pathway, occurs in almost 80% of CRC cases. The progression of this cancer from an early adenoma to carcinoma is accompanied by a well-characterised set of mutations including KRAS, SMAD4 and TP53. Using elegant genetic models the current paradigm is that the intestinal stem cell is the origin of CRC. However, human histology and recent studies, showing marked plasticity within the intestinal epithelium, may point to other cells of origin. Here we will review these latest studies and place these in context to provide an up-to-date view of the cell of origin of CRC. PMID:26110974

  7. Differentially expressed microRNAs in colorectal cancer metastasis

    PubMed Central

    Abba, Mohammed; Benner, Axel; Patil, Nitin; Heil, Oliver; Allgayer, Heike

    2015-01-01

    Tumor metastasis continues to be the most significant contributor to cancer related mortality, and although several studies have examined expression profiles emanating from patients with metastatic disease, very little information is available about signatures that differentiate metastatic lesions from primary tumors and associated normal tissues, largely because such matched tissue sample series are rare. This study was specifically designed to identify the metastasis relevant microRNAs in colorectal cancer and characterize microRNAs that modulate the metastatic phenotype. Here we describe in detail how the data, deposited in the Gene Expression Omnibus (GEO) with the accession number GSE54088, was generated including the basic analysis as contained in the manuscript published in Cancer Research with the PMID 26069251. PMID:26697326

  8. Colorectal cancer screening: a global overview of existing programmes.

    PubMed

    Schreuders, Eline H; Ruco, Arlinda; Rabeneck, Linda; Schoen, Robert E; Sung, Joseph J Y; Young, Graeme P; Kuipers, Ernst J

    2015-10-01

    Colorectal cancer (CRC) ranks third among the most commonly diagnosed cancers worldwide, with wide geographical variation in incidence and mortality across the world. Despite proof that screening can decrease CRC incidence and mortality, CRC screening is only offered to a small proportion of the target population worldwide. Throughout the world there are widespread differences in CRC screening implementation status and strategy. Differences can be attributed to geographical variation in CRC incidence, economic resources, healthcare structure and infrastructure to support screening such as the ability to identify the target population at risk and cancer registry availability. This review highlights issues to consider when implementing a CRC screening programme and gives a worldwide overview of CRC burden and the current status of screening programmes, with focus on international differences.

  9. Autophagy in colorectal cancer: An important switch from physiology to pathology

    PubMed Central

    Burada, Florin; Nicoli, Elena Raluca; Ciurea, Marius Eugen; Uscatu, Daniel Constantin; Ioana, Mihai; Gheonea, Dan Ionut

    2015-01-01

    Colorectal cancer (CRC) remains a leading cause of cancer death in both men and women worldwide. Among the factors and mechanisms that are involved in the multifactorial etiology of CRC, autophagy is an important transformational switch that occurs when a cell shifts from normal to malignant. In recent years, multiple hypotheses have been considered regarding the autophagy mechanisms that are involved in cancer. The currently accepted hypothesis is that autophagy has dual and contradictory roles in carcinogenesis, but the precise mechanisms leading to autophagy in cancer are not yet fully defined and seem to be context dependent. Autophagy is a surveillance mechanism used by normal cells that protects them from the transformation to malignancy by removing damaged organelles and aggregated proteins and by reducing reactive oxygen species, mitochondrial abnormalities and DNA damage. However, autophagy also supports tumor formation by promoting access to nutrients that are critical to the metabolism and growth of tumor cells and by inhibiting cellular death and increasing drug resistance. Autophagy studies in CRC have focused on several molecules, mainly microtubule-associated protein 1 light chain 3, beclin 1, and autophagy related 5, with conflicting results. Beneficial effects were observed for some agents that modulate autophagy in CRC either alone or, more often, in combination with other agents. More extensive studies are needed in the future to clarify the roles of autophagy-related genes and modulators in colorectal carcinogenesis, and to develop potential beneficial agents for the prognosis and treatment of CRC. PMID:26600927

  10. Spatial Heterogeneity Analysis in Evaluation of Cell Viability and Apoptosis for Colorectal Cancer Cells

    PubMed Central

    Kucharavy, Herman; Hubbard, Karen; Uyar, Muharrem Ümit

    2016-01-01

    In evaluation of cell viability and apoptosis, spatial heterogeneity is quantified for cancerous cells cultured in 3-D in vitro cell-based assays under the impact of anti-cancer agents. In 48-h experiments using human colorectal cancer cell lines of HCT-116, SW-620, and SW-480, incubated cells are divided into control and drug administered groups, to be grown in matrigel and FOLFOX solution, respectively. Our 3-D cell tracking and data acquisition system guiding an inverted microscope with a digital camera is utilized to capture bright field and fluorescent images of colorectal cancer cells at multiple time points. Identifying the locations of live and dead cells in captured images, spatial point process and Voronoi tessellation methods are applied to extract morphological features of in vitro cell-based assays. For the former method, spatial heterogeneity is quantified with the second-order functions of Poisson point process, whereas the deviation in the area of Voronoi polygons is computed for the latter. With both techniques, the results indicate that the spatial heterogeneity of live cell locations increases as the viability of in in vitro cell cultures decreases. On the other hand, a decrease is observed for the heterogeneity of dead cell locations with the decrease in cell viability. This relationship between morphological features of in vitro cell-based assays and cell viability can be used for drug efficacy measurements and utilized as a biomarker for 3-D in vitro microenvironment assays. PMID:27574578

  11. Spatial Heterogeneity Analysis in Evaluation of Cell Viability and Apoptosis for Colorectal Cancer Cells.

    PubMed

    Saribudak, Aydin; Kucharavy, Herman; Hubbard, Karen; Uyar, Muharrem Umit

    2016-01-01

    In evaluation of cell viability and apoptosis, spatial heterogeneity is quantified for cancerous cells cultured in 3-D in vitro cell-based assays under the impact of anti-cancer agents. In 48-h experiments using human colorectal cancer cell lines of HCT-116, SW-620, and SW-480, incubated cells are divided into control and drug administered groups, to be grown in matrigel and FOLFOX solution, respectively. Our 3-D cell tracking and data acquisition system guiding an inverted microscope with a digital camera is utilized to capture bright field and fluorescent images of colorectal cancer cells at multiple time points. Identifying the locations of live and dead cells in captured images, spatial point process and Voronoi tessellation methods are applied to extract morphological features of in vitro cell-based assays. For the former method, spatial heterogeneity is quantified with the second-order functions of Poisson point process, whereas the deviation in the area of Voronoi polygons is computed for the latter. With both techniques, the results indicate that the spatial heterogeneity of live cell locations increases as the viability of in in vitro cell cultures decreases. On the other hand, a decrease is observed for the heterogeneity of dead cell locations with the decrease in cell viability. This relationship between morphological features of in vitro cell-based assays and cell viability can be used for drug efficacy measurements and utilized as a biomarker for 3-D in vitro microenvironment assays. PMID:27574578

  12. A targeted molecular probe for colorectal cancer imaging

    NASA Astrophysics Data System (ADS)

    Attramadal, T.; Bjerke, R.; Indrevoll, B.; Moestue, S.; Rogstad, A.; Bendiksen, R.; Healey, A.; Johannesen, E.

    2008-02-01

    Colorectal cancer is a major cause of cancer death. Morbidity, mortality and healthcare costs can be reduced if the disease can be detected at an early stage. Screening is a viable approach as there is a clear link to risk factors such as age. We have developed a fluorescent contrast agent for use during colonoscopy. The agent is administered intravenously and is targeted to an early stage molecular marker for colorectal cancer. The agent consists of a targeting section comprising a peptide, and a fluorescent reporter molecule. Clinical imaging of the agent is to be performed with a far red fluorescence imaging channel (635 nm excitation/660-700 nm emission) as an adjunct to white light colonoscopy. Preclinical proof of mechanism results are presented. The compound has a K d of ~3nM. Two human xenograft tumour models were used. Tumour cells were implanted and grown subcutaneously in nude mice. Imaging using a fluorescence reflectance imaging system and quantitative biodistribution studies were performed. Substances tested include the targeted agent, and a scrambled sequence of the peptide (no binding) used as a negative control. Competition studies were also performed by co-administration of 180 times excess unlabelled peptide. Positive imaging contrast was shown in the tumours, with a clear relationship to expression levels (confirmed with quantitative biodistribution data). There was a significant difference between the positive and negative control substances, and a significant reduction in contrast in the competition experiment.

  13. History and present status of pulmonary metastasectomy in colorectal cancer

    PubMed Central

    Treasure, Tom; Milošević, Mišel; Fiorentino, Francesca; Pfannschmidt, Joachim

    2014-01-01

    Clinical practice with respect to metastatic colorectal cancer differs from the other two most common cancers, breast and lung, in that routine surveillance is recommended with the specific intent of detecting liver and lung metastases and undertaking liver and lung resections for their removal. We trace the history of this approach to colorectal cancer by reviewing evidence for effectiveness from the 1950s to the present day. Our sources included published citation network analyses, the documented proposal for randomised trials, large systematic reviews, and meta-analysis of observational studies. The present consensus position has been adopted on the basis of a large number of observational studies but the randomised trials proposed in the 1980s and 1990s were either not done, or having been done, were not reported. Clinical opinion is the mainstay of current practice but in the absence of randomised trials there remains a possibility of selection bias. Randomised controlled trials (RCTs) are now routine before adoption of a new practice but RCTs are harder to run in evaluation of already established practice. One such trial is recruiting and shows that controlled trial are possible. PMID:25356017

  14. Mutations in the circadian gene CLOCK in colorectal cancer.

    PubMed

    Alhopuro, Pia; Björklund, Mikael; Sammalkorpi, Heli; Turunen, Mikko; Tuupanen, Sari; Biström, Mia; Niittymäki, Iina; Lehtonen, Heli J; Kivioja, Teemu; Launonen, Virpi; Saharinen, Juha; Nousiainen, Kari; Hautaniemi, Sampsa; Nuorva, Kyösti; Mecklin, Jukka-Pekka; Järvinen, Heikki; Orntoft, Torben; Arango, Diego; Lehtonen, Rainer; Karhu, Auli; Taipale, Jussi; Aaltonen, Lauri A

    2010-07-01

    The circadian clock regulates daily variations in physiologic processes. CLOCK acts as a regulator in the circadian apparatus controlling the expression of other clock genes, including PER1. Clock genes have been implicated in cancer-related functions; in this work, we investigated CLOCK as a possible target of somatic mutations in microsatellite unstable colorectal cancers. Combining microarray gene expression data and public gene sequence information, we identified CLOCK as 1 of 790 putative novel microsatellite instability (MSI) target genes. A total of 101 MSI colorectal carcinomas (CRC) were sequenced for a coding microsatellite in CLOCK. The effect of restoring CLOCK expression was studied in LS180 cells lacking wild-type CLOCK by stably expressing GST-CLOCK or glutathione S-transferase empty vector and testing the effects of UV-induced apoptosis and radiation by DNA content analysis using flow cytometry. Putative novel CLOCK target genes were searched by using ChIP-seq. CLOCK mutations occurred in 53% of MSI CRCs. Restoring CLOCK expression in cells with biallelic CLOCK inactivation resulted in protection against UV-induced apoptosis and decreased G(2)-M arrest in response to ionizing radiation. Using ChIP-Seq, novel CLOCK-binding elements were identified near DNA damage genes p21, NBR1, BRCA1, and RAD50. CLOCK is shown to be mutated in cancer, and altered response to DNA damage provides one plausible mechanism of tumorigenesis.

  15. Biomarker-directed Targeted Therapy in Colorectal Cancer

    PubMed Central

    Carethers, John M.

    2015-01-01

    With advances in the understanding of the biology and genetics of colorectal cancer (CRC), diagnostic biomarkers that may predict the existence or future presence of cancer or a hereditary condition, and prognostic and treatment biomarkers that may direct the approach to therapy have been developed. Biomarkers can be ascertained and assayed from any tissue that may demonstrate the diagnostic or prognostic value, including from blood cells, epithelial cells via buccal swab, fresh or archival cancer tissue, as well as from cells shed into fecal material. For CRC, current examples of biomarkers for screening and surveillance include germline testing for suspected hereditary CRC syndromes, and stool DNA tests for screening average at-risk patients. Molecular biomarkers for CRC that may alter patient care and treatment include the presence or absence of microsatellite instability, the presence or absence of mutant KRAS, BRAF or PIK3CA, and the level of expression of 15-PGDH in the colorectal mucosa. Molecularly targeted therapies and some general therapeutic approaches rely on biomarker information. Additional novel biomarkers are on the horizon that will undoubtedly further the approach to precision or individualized medicine. PMID:26609516

  16. Treatment of metastatic colorectal cancer: focus on panitumumab

    PubMed Central

    Tay, Rebecca Y; Wong, Rachel; Hawkes, Eliza A

    2015-01-01

    Targeted agents are an important therapeutic option in the treatment of metastatic colorectal cancer (mCRC). Panitumumab is a recombinant, fully humanized, immunoglobulin G2 monoclonal antibody that targets the epidermal growth factor receptor (EGFR) with efficacy in mCRC as monotherapy and in combination with chemotherapy. Kirsten rat sarcoma (KRAS) mutation status has emerged as an important biomarker to predict response to anti-EGFR therapy. Optimal timing for panitumumab use in the mCRC treatment algorithm has not been established. This review discusses the mechanism of action, predictive biomarkers, and role of panitumumab in the treatment of mCRC. PMID:26150735

  17. First-line therapeutic strategies in metastatic colorectal cancer.

    PubMed

    Davies, Janine M; Goldberg, Richard M

    2008-11-30

    The treatment of metastatic colorectal cancer (mCRC) has changed dramatically from the 1980s, when only fluorouracil (5-FU) was available for treatment and the median survival was at best 12 months, to a time when mCRC is considered more of a chronic disease in which the median survival is now reported in excess of 2 years. This review traces the evolution of treatment in this setting, including studies of single-agent vs combination treatment with 5-FU/leucovorin, irinotecan, oxaliplatin, and capecitabine, comparisons of simultaneous and sequential regimens, and the role of targeted agents such as bevacizumab, cetuximab, and panitumumab. PMID:19133603

  18. Changing trends in colorectal cancer in the Republic of Korea: contrast with Japan

    PubMed Central

    Yoon, Minjoo; Kim, Nicholas; Nam, Byungho; Joo, Jungnam; Ki, Moran

    2015-01-01

    Colorectal cancer has a high worldwide incidence. Japan, a country that is geographically and culturally similar to the Republic of Korea (here after Korea), has recently reported a decreasing trend in the incidence of colorectal cancer. However, Korea had the highest incidence of colorectal cancer among Asian countries in 2012. Our aim was to observe the changing trends in incidence and mortality of colorectal cancer in Korea and to compare them to those in Japan. Incidence data were collected from the Korean Central Cancer Registry and mortality data were collected from Korean Statistical Information Service. Incidence and mortality data on colorectal cancer in Japan were acquired from the National Cancer Center in Japan. Age-standardized incidence and mortality rates were determined based on Segi’s world population. Screening data from both countries were collected from the national cancer center in each country. In Korea, the age-standardized incidence rate of colorectal cancer in both sexes was 20.9 to 38.0 per 100,000 from 1999 to 2012 and the rate in males increased more dramatically than in females. In addition, the increase between 2002 and 2012 was first observed in the age group over 40. In Japan, the incidence of colorectal cancer has been more constant over recent years than in Korea. The age-standardized mortality rate of colorectal cancer in both sexes in Korea was 8.5 to 9.3 per 100,000 from 2000 to 2013, and the trend in mortality was constant during this period. In Japan, the mortality rate decreased slightly during the same period. Crude screening rates were increased overall in both Korea and Japan during the period studied. Since the incidence of colorectal cancer has increased in Korea, the control of this cancer is an important public health issue. As Japan has achieved a reduction in colorectal cancer, adjustment of Korea’s current systems for screening and treatment of colorectal cancer according to those of Japan may contribute to

  19. The Inositide Signaling Pathway As a Target for Treating Gastric Cancer and Colorectal Cancer

    PubMed Central

    Kim, Hong Jun; Lee, Suk-young; Oh, Sang Cheul

    2016-01-01

    Gastric cancer and colorectal cancer are the leading cause of cancer mortality and have a dismal prognosis. The introduction of biological agents to treat these cancers has resulted in improved outcomes, and combination chemotherapy with targeted agents and conventional chemotherapeutic agents is regarded as standard therapy. Additional newly clarified mechanisms of oncogenesis and resistance to targeted agents require the development of new biologic agents. Aberrant activation of the inositide signaling pathway by a loss of function PTEN mutation or gain of function mutation/amplification of PIK3CA is an oncogenic mechanism in gastric cancer and colorectal cancer. Clinical trials with biologic agents that target the inositide signaling pathway are being performed to further improve treatment outcomes of patients with advanced gastric cancer and metastatic colorectal cancer (CRC). In this review we summarize the inositide signaling pathway, the targeted agents that inhibit abnormal activation of this signaling pathway and the clinical trials currently being performed in patients with advanced or metastatic gastric cancer and metastatic CRC using these targeted agents. PMID:27242542

  20. Meat-Related Compounds and Colorectal Cancer Risk by Anatomical Subsite

    PubMed Central

    Miller, Paige E.; Lazarus, Philip; Lesko, Samuel M.; Cross, Amanda J.; Sinha, Rashmi; Laio, Jason; Zhu, Jay; Harper, Gregory; Muscat, Joshua E.; Hartman, Terryl J.

    2012-01-01

    Since meat may be involved in the etiology of colorectal cancer, associations between meat-related compounds were examined to elucidate underlying mechanisms in a population-based case-control study. Participants (989 cases/1,033 healthy controls) completed a food frequency questionnaire with a meat-specific module. Multivariable logistic regression was used to examine associations between meat variables and colorectal cancer; polytomous logistic regression was used for subsite-specific analyses. The following significant positive associations were observed for meat-related compounds: 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and colorectal, distal colon, and rectal tumors; 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and colorectal and colon cancer tumors; nitrites/nitrates and proximal colon cancer; 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and rectal cancer; and benzo[a]pyrene and rectal cancer (P-trends < 0.05 ). For analyses by meat type, cooking method, and doneness preference, positive associations between red processed meat and proximal colon cancer and pan-fried red meat and colorectal cancer were found (P-trends < 0.05). Inverse associations were observed between unprocessed poultry and colorectal, colon, proximal colon, and rectal tumors; grilled/barbequed poultry and proximal colon cancer; and well-done/charred poultry and colorectal, colon, and proximal colon tumors (P-trends < 0.05). HCAs, PAHs, nitrites, and nitrates may be involved in colorectal cancer etiology. Further examination into the unexpected inverse associations between poultry and colorectal cancer is warranted. PMID:23441608

  1. Dietary Total Antioxidant Capacity and Colorectal Cancer in the Italian EPIC Cohort

    PubMed Central

    Vece, Marilena Monica; Agnoli, Claudia; Grioni, Sara; Sieri, Sabina; Pala, Valeria; Pellegrini, Nicoletta; Frasca, Graziella; Tumino, Rosario; Mattiello, Amalia; Panico, Salvatore; Bendinelli, Benedetta; Masala, Giovanna; Ricceri, Fulvio; Sacerdote, Carlotta; Krogh, Vittorio

    2015-01-01

    Background Colorectal cancer is the third most common cancer worldwide. Diet has been hypothesized as involved in colorectal cancer etiology, but few studies on the influence of total dietary antioxidant intake on colorectal cancer risk have been performed. Methods We investigated the association between colorectal cancer risk and the total antioxidant capacity (TAC) of the diet, and also of intake of selected antioxidants, in 45,194 persons enrolled in 5 centers (Florence, Naples, Ragusa, Turin and Varese) of the European Prospective Investigation into Cancer and Nutrition (EPIC) Italy study. TAC was estimated by the Trolox equivalent antioxidant capacity (TEAC) assay. Hazard ratios (HRs) for developing colorectal cancer, and colon and rectal cancers separately, adjusted for confounders, were estimated for tertiles of TAC by Cox modeling, stratifying by center. Results Four hundred thirty-six colorectal cancers were diagnosed over a mean follow-up of 11.28 years. No significant association between dietary TAC and colorectal cancer incidence was found. However for the highest category of TAC compared to the lowest, risk of developing colon cancer was lower (HR: 0.63; 95% CI: 0.44–0.89, P trend: 0.008). By contrast, increasing TAC intake was associated with significantly increasing risks of rectal cancer (2nd tertile HR: 2.09; 95%CI: 1.19–3.66; 3rd tertile 2.48 95%CI: 1.32–4.66; P trend 0.007). Intakes of vitamin C, vitamin E, and ß-carotene were not significantly associated with colorectal cancer risk. Conclusions Further prospective studies are needed to confirm the contrasting effects of high total antioxidant intake on risk of colon and rectal cancers. PMID:26565695

  2. N-glycoprotein analysis discovers new up-regulated glycoproteins in colorectal cancer tissue.

    PubMed

    Nicastri, Annalisa; Gaspari, Marco; Sacco, Rosario; Elia, Laura; Gabriele, Caterina; Romano, Roberto; Rizzuto, Antonia; Cuda, Giovanni

    2014-11-01

    Colorectal cancer is one of the leading causes of death due to cancer worldwide. Therefore, the identification of high-specificity and -sensitivity biomarkers for the early detection of colorectal cancer is urgently needed. Post-translational modifications, such as glycosylation, are known to play an important role in cancer progression. In the present work, we used a quantitative proteomic technique based on (18)O stable isotope labeling to identify differentially expressed N-linked glycoproteins in colorectal cancer tissue samples compared with healthy colorectal tissue from 19 patients undergoing colorectal cancer surgery. We identified 54 up-regulated glycoproteins in colorectal cancer samples, therefore potentially involved in the biological processes of tumorigenesis. In particular, nine of these (PLOD2, DPEP1, SE1L1, CD82, PAR1, PLOD3, S12A2, LAMP3, OLFM4) were found to be up-regulated in the great majority of the cohort, and, interestingly, the association with colorectal cancer of four (PLOD2, S12A2, PLOD3, CD82) has not been hitherto described.

  3. Using lessons from breast, cervical, and colorectal cancer screening to inform the development of lung cancer screening programs.

    PubMed

    Armstrong, Katrina; Kim, Jane J; Halm, Ethan A; Ballard, Rachel M; Schnall, Mitchell D

    2016-05-01

    Multiple advisory groups now recommend that high-risk smokers be screened for lung cancer by low-dose computed tomography. Given that the development of lung cancer screening programs will face many of the same issues that have challenged other cancer screening programs, the National Cancer Institute-funded Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium was used to identify lessons learned from the implementation of breast, cervical, and colorectal cancer screening that should inform the introduction of lung cancer screening. These lessons include the importance of developing systems for identifying and recruiting eligible individuals in primary care, ensuring that screening centers are qualified and performance is monitored, creating clear communication standards for reporting screening results to referring physicians and patients, ensuring follow-up is available for individuals with abnormal test results, avoiding overscreening, remembering primary prevention, and leveraging advances in cancer genetics and immunology. Overall, this experience emphasizes that effective cancer screening is a multistep activity that requires robust strategies to initiate, report, follow up, and track each step as well as a dynamic and ongoing oversight process to revise current screening practices as new evidence regarding screening is created, new screening technologies are developed, new biological markers are identified, and new approaches to health care delivery are disseminated. Cancer 2016;122:1338-1342. © 2016 American Cancer Society. PMID:26929386

  4. VE1 immunohistochemistry predicts BRAF V600E mutation status and clinical outcome in colorectal cancer

    PubMed Central

    Schafroth, Christian; Galván, José A.; Centeno, Irene; Koelzer, Viktor H.; Dawson, Heather E.; Sokol, Lena; Rieger, Gregor; Berger, Martin D.; Hädrich, Marion; Rosenberg, Robert; Nitsche, Ulrich; Schnüriger, Beat; Langer, Rupert; Inderbitzin, Daniel; Lugli, Alessandro; Zlobec, Inti

    2015-01-01

    Aim VE1 is a monoclonal antibody detecting mutant BRAFV600E protein by immunohistochemistry. Here we aim to determine the inter-observer agreement and concordance of VE1 with mutational status, investigate heterogeneity in colorectal cancers and metastases and determine the prognostic effect of VE1 in colorectal cancer patients. Methods Concordance of VE1 with mutational status and inter-observer agreement were tested on a pilot cohort of colorectal cancers (n = 34), melanomas (n = 23) and thyroid cancers (n = 8). Two prognostic cohorts were evaluated (n = 259, Cohort 1 and n = 226, Cohort 2) by multiple-punch tissue microarrays. VE1 staining on preoperative biopsies (n = 118 patients) was compared to expression in resections. Primary tumors and metastases from 13 patients were tested for VE1 heterogeneity using a tissue microarray generated from all available blocks (n = 100 blocks). Results Inter-observer agreement was 100% (kappa = 1.0). Concordance between VE1 and V600E mutation was 98.5%. Cohort 1: VE1 positivity (seen in 13.5%) was associated with older age (p = 0.0175) and MLH1 deficiency (p < 0.0001). Cohort 2: VE1 positivity (seen in 12.8%) was associated with female gender (p = 0.0016), right-sided tumor location (p < 0.0001), higher tumor grade (p < 0.0001) and mismatch repair (MMR)-deficiency (p < 0.0001). In survival analysis, MMR status and postoperative therapy were identified as possible confounding factors. Adjusting for these features, VE1 was an unfavorable prognostic factor. Preoperative biopsy staining matched resections in all cases except one. No heterogeneity was found across any primary/metastatic tumor blocks. Conclusion VE1 is highly concordant for V600E and homogeneously expressed suggesting staining can be analysed on resection specimens, preoperative biopsies, metastatic lesions and tissue microarrays. PMID:26496026

  5. Plasma Alkylresorcinols, Biomarkers of Whole-Grain Wheat and Rye Intake, and Incidence of Colorectal Cancer

    PubMed Central

    2014-01-01

    Background Few studies have investigated the association between whole-grain intake and colorectal cancer. Because whole-grain intake estimation might be prone to measurement errors, more objective measures (eg, biomarkers) could assist in investigating such associations. Methods The association between alkylresorcinols, biomarkers of whole-grain rye and wheat intake, and colorectal cancer incidence were investigated using prediagnostic plasma samples from colorectal cancer case patients and matched control subjects nested within the European Prospective Investigation into Cancer and Nutrition. We included 1372 incident colorectal cancer case patients and 1372 individual matched control subjects and calculated the incidence rate ratios (IRRs) for overall and anatomical subsites of colorectal cancer using conditional logistic regression adjusted for potential confounders. Regional differences (Scandinavia, the Mediterranean, Central Europe) were also explored. Results High plasma total alkylresorcinol concentration was associated with lower incidence of distal colon cancer; the adjusted incidence rate ratio of distal colon cancer for the highest vs lowest quartile of plasma total alkylresorcinols was 0.48 (95% confidence interval [CI] = 0.28 to 0.83). An inverse association between plasma total alkylresorcinol concentrations and colon cancer was found for Scandinavian participants (IRR per doubling = 0.83; 95% CI = 0.70 to 0.98). However, plasma total alkylresorcinol concentrations were not associated with overall colorectal cancer, proximal colon cancer, or rectal cancer. Plasma alkylresorcinols concentrations were associated with colon and distal colon cancer only in Central Europe and Scandinavia (ie, areas where alkylresorcinol levels were higher). Conclusions High concentrations of plasma alkylresorcinols were associated with a lower incidence of distal colon cancer but not with overall colorectal cancer, proximal colon cancer, and rectal cancer. PMID:24317181

  6. Exome sequencing of a colorectal cancer family reveals shared mutation pattern and predisposition circuitry along tumor pathways

    PubMed Central

    Suleiman, Suleiman H.; Koko, Mahmoud E.; Nasir, Wafaa H.; Elfateh, Ommnyiah; Elgizouli, Ubai K.; Abdallah, Mohammed O. E.; Alfarouk, Khalid O.; Hussain, Ayman; Faisal, Shima; Ibrahim, Fathelrahamn M. A.; Romano, Maurizio; Sultan, Ali; Banks, Lawrence; Newport, Melanie; Baralle, Francesco; Elhassan, Ahmed M.; Mohamed, Hiba S.; Ibrahim, Muntaser E.

    2015-01-01

    The molecular basis of cancer and cancer multiple phenotypes are not yet fully understood. Next Generation Sequencing promises new insight into the role of genetic interactions in shaping the complexity of cancer. Aiming to outline the differences in mutation patterns between familial colorectal cancer cases and controls we analyzed whole exomes of cancer tissues and control samples from an extended colorectal cancer pedigree, providing one of the first data sets of exome sequencing of cancer in an African population against a background of large effective size typically with excess of variants. Tumors showed hMSH2 loss of function SNV consistent with Lynch syndrome. Sets of genes harboring insertions–deletions in tumor tissues revealed, however, significant GO enrichment, a feature that was not seen in control samples, suggesting that ordered insertions–deletions are central to tumorigenesis in this type of cancer. Network analysis identified multiple hub genes of centrality. ELAVL1/HuR showed remarkable centrality, interacting specially with genes harboring non-synonymous SNVs thus reinforcing the proposition of targeted mutagenesis in cancer pathways. A likely explanation to such mutation pattern is DNA/RNA editing, suggested here by nucleotide transition-to-transversion ratio that significantly departed from expected values (p-value 5e-6). NFKB1 also showed significant centrality along with ELAVL1, raising the suspicion of viral etiology given the known interaction between oncogenic viruses and these proteins. PMID:26442106

  7. TroVax in colorectal cancer

    PubMed Central

    Rowe, Julie; Cen, Putao

    2014-01-01

    Currently, the backbone of therapy for metastatic disease is cytotoxic chemotherapy, along with the recent addition of targeted therapy based on molecular markers with KRAS testing. Despite the improvement in survival for metastatic colon cancer, newer agents are still needed. The clinical activity of TroVax in metastatic colon cancer has been studied in a small number of clinical trials. There is evidence that supports the vaccine's ability to induce humoral and cellular responses, as demonstrated by positive 5T4 and MVA-specific antibody titers and cellular proliferation assays. Future strategies should focus on investigating the immunomodulatory effects of chemotherapy in conjunction with TroVax, understanding the optimal dosing and schedule of the combination, and examining potential predictive biomarkers to determine which patients may benefit from immunotherapy from those who do not. PMID:25483641

  8. Patients with genetically heterogeneous synchronous colorectal cancer carry rare damaging germline mutations in immune-related genes.

    PubMed

    Cereda, Matteo; Gambardella, Gennaro; Benedetti, Lorena; Iannelli, Fabio; Patel, Dominic; Basso, Gianluca; Guerra, Rosalinda F; Mourikis, Thanos P; Puccio, Ignazio; Sinha, Shruti; Laghi, Luigi; Spencer, Jo; Rodriguez-Justo, Manuel; Ciccarelli, Francesca D

    2016-01-01

    Synchronous colorectal cancers (syCRCs) are physically separated tumours that develop simultaneously. To understand how the genetic and environmental background influences the development of multiple tumours, here we conduct a comparative analysis of 20 syCRCs from 10 patients. We show that syCRCs have independent genetic origins, acquire dissimilar somatic alterations, and have different clone composition. This inter- and intratumour heterogeneity must be considered in the selection of therapy and in the monitoring of resistance. SyCRC patients show a higher occurrence of inherited damaging mutations in immune-related genes compared to patients with solitary colorectal cancer and to healthy individuals from the 1,000 Genomes Project. Moreover, they have a different composition of immune cell populations in tumour and normal mucosa, and transcriptional differences in immune-related biological processes. This suggests an environmental field effect that promotes multiple tumours likely in the background of inflammation. PMID:27377421

  9. Patients with genetically heterogeneous synchronous colorectal cancer carry rare damaging germline mutations in immune-related genes

    PubMed Central

    Cereda, Matteo; Gambardella, Gennaro; Benedetti, Lorena; Iannelli, Fabio; Patel, Dominic; Basso, Gianluca; Guerra, Rosalinda F.; Mourikis, Thanos P.; Puccio, Ignazio; Sinha, Shruti; Laghi, Luigi; Spencer, Jo; Rodriguez-Justo, Manuel; Ciccarelli, Francesca D.

    2016-01-01

    Synchronous colorectal cancers (syCRCs) are physically separated tumours that develop simultaneously. To understand how the genetic and environmental background influences the development of multiple tumours, here we conduct a comparative analysis of 20 syCRCs from 10 patients. We show that syCRCs have independent genetic origins, acquire dissimilar somatic alterations, and have different clone composition. This inter- and intratumour heterogeneity must be considered in the selection of therapy and in the monitoring of resistance. SyCRC patients show a higher occurrence of inherited damaging mutations in immune-related genes compared to patients with solitary colorectal cancer and to healthy individuals from the 1,000 Genomes Project. Moreover, they have a different composition of immune cell populations in tumour and normal mucosa, and transcriptional differences in immune-related biological processes. This suggests an environmental field effect that promotes multiple tumours likely in the background of inflammation. PMID:27377421

  10. Patient Navigation in a Colorectal Cancer Screening Program

    PubMed Central

    Escoffery, Cam; Fernandez, Maria E.; Vernon, Sally W.; Liang, Shuting; Maxwell, Annette E.; Allen, Jennifer D.; Dwyer, Andrea; Hannon, Peggy A.; Kohn, Marlana; DeGroff, Amy

    2015-01-01

    Context Colorectal cancer (CRC) is the second leading cause of cancer death among cancers affecting both men and women in the United States. The Centers for Disease Control and Prevention’s Colorectal Cancer Control Program (CRCCP) supports both direct clinical screening services (screening provision) and activities to promote screening at the population level (screening promotion). Objective The purpose of this study was to characterize patient navigation (PN) programs for screening provision and promotion for the first 1 to 2 years of program funding. Participants We conducted a cross-sectional survey of the 29 CRCCP grantees (25 states and 4 tribal organizations) and 14 in-depth interviews to assess program implementation. Main Outcome Measures The survey and interview guide collected information on CRC screening provision and promotion activities and PN, including the structure of the PN program, characteristics of the navigators, funding mechanism, and navigators’ activities. Results Twenty-four of 28 CRCCP grantees of the survey used PN for screening provision whereas 18 grantees used navigation for screening promotion. Navigators were often trained in nursing or public health. Navigation activities were similar for both screening provision and promotion, and common tasks included assessing and responding to patient barriers to screening, providing patient education, and scheduling appointments. For screening provision, activities centered on making reminder calls, educating patients on bowel preparation for colonoscopies, and tracking patients for completion of the tests. Navigation may influence screening quality by improving patients’ bowel preparation for colonoscopies. Conclusions Our study provides insights into PN across a federally funded CRC program. Results suggest that PN activities may be instrumental in recruiting people into cancer screening and ensuring completed screening and follow-up. PMID:25140407

  11. Developing Screening Services for Colorectal Cancer on Android Smartphones

    PubMed Central

    Wu, Hui-Ching; Chang, Chiao-Jung; Lin, Chun-Che; Tsai, Ming-Chang; Chang, Che-Chia

    2014-01-01

    Abstract Introduction: Colorectal cancer (CRC) is an important health problem in Western countries and also in Asia. It is the third leading cause of cancer deaths in both men and women in Taiwan. According to the well-known adenoma-to-carcinoma sequence, the majority of CRC develops from colorectal adenomatous polyps. This concept provides the rationale for screening and prevention of CRC. Removal of colorectal adenoma could reduce the mortality and incidence of CRC. Mobile phones are now playing an ever more crucial role in people's daily lives. The latest generation of smartphones is increasingly viewed as hand-held computers rather than as phones, because of their powerful on-board computing capability, capacious memories, large screens, and open operating systems that encourage development of applications (apps). Subjects and Methods: If we can detect the potential CRC patients early and offer them appropriate treatments and services, this would not only promote the quality of life, but also reduce the possible serious complications and medical costs. In this study, an intelligent CRC screening app on Android™ (Google™, Mountain View, CA) smartphones has been developed based on a data mining approach using decision tree algorithms. For comparison, the stepwise backward multivariate logistic regression model and the fecal occult blood test were also used. Results: Compared with the stepwise backward multivariate logistic regression model and the fecal occult blood test, the proposed app system not only provides an easy and efficient way to quickly detect high-risk groups of potential CRC patients, but also brings more information about CRC to customer-oriented services. Conclusions: We developed and implemented an app system on Android platforms for ubiquitous healthcare services for CRC screening. It can assist people in achieving early screening, diagnosis, and treatment purposes, prevent the occurrence of complications, and thus reach the goal of

  12. Colorectal cancer screening practices of primary care providers: results of a national survey in Malaysia.

    PubMed

    Norwati, Daud; Harmy, Mohamed Yusoff; Norhayati, Mohd Noor; Amry, Abdul Rahim

    2014-01-01

    The incidence of colorectal cancer has been increasing in many Asian countries including Malaysia during the past few decades. A physician recommendation has been shown to be a major factor that motivates patients to undergo screening. The present study objectives were to describe the practice of colorectal cancer screening by primary care providers in Malaysia and to determine the barriers for not following recommendations. In this cross sectional study involving 132 primary care providers from 44 Primary Care clinics in West Malaysia, self-administered questionnaires which consisted of demographic data, qualification, background on the primary care clinic, practices on colorectal cancer screening and barriers to colorectal cancer screening were distributed. A total of 116 primary care providers responded making a response rate of 87.9%. About 21% recommended faecal occult blood test (FOBT) in more than 50% of their patients who were eligible. The most common barrier was "unavailability of the test". The two most common patient factors are "patient in a hurry" and "poor patient awareness". This study indicates that colorectal cancer preventive activities among primary care providers are still poor in Malaysia. This may be related to the low availability of the test in the primary care setting and poor awareness and understanding of the importance of colorectal cancer screening among patients. More awareness programmes are required for the public. In addition, primary care providers should be kept abreast with the latest recommendations and policy makers need to improve colorectal cancer screening services in health clinics.

  13. Panitumumab: the evidence of its therapeutic potential in metastatic colorectal cancer care

    PubMed Central

    Martinelli, Erika; Morgillo, Floriana; Troiani, Teresa; Tortora, Giampaolo; Ciardiello, Fortunato

    2007-01-01

    Introduction: Colorectal cancer is the fourth most common malignant disease. Of newly diagnosed patients, 40% have metastatic disease at diagnosis, and approximately 25% of patients with localized disease at diagnosis will ultimately develop metastatic disease. The benefits of systemic chemotherapy in the treatment of metastatic colorectal cancer over best supportive care have been established. Panitumumab (ABX-EGF) is the first fully human monoclonal antibody developed for use in colorectal cancer that targets the extracellular domains of epidermal growth factor receptor. Aims: The goal of this article is to review the published evidence for the use of panitumumab in the treatment of metastatic colorectal cancer to define its therapeutic potential. Evidence review: The major evidence of panitumumab activity in colorectal cancer has appeared in meeting report abstracts. One phase II study in monotherapy, one in combination with chemotherapy, and one phase III study have included only patients with metastatic colorectal cancer. Clinical potential: To date, in phase II clinical studies panitumumab has demonstrated antitumor activity in advanced, refractory colorectal cancer. As monotherapy it resulted in a 10% response rate with 38% of patients having stable disease, and a 36% response rate with 46% stable disease when combined with chemotherapy. A phase III study indicates a clinically significant advantage of panitumumab as third-line monotherapy over best supportive care. Panitumumab appears to have a good tolerability profile, with no maximum tolerated dose yet defined. PMID:21221177

  14. Use of biguanides and the risk of colorectal cancer: a register-based cohort study.

    PubMed

    Knapen, Lotte M; Dittrich, Suzanne T A M; de Vries, Frank; Starup-Linde, Jakob; Vestergaard, Peter; Henry, Ronald M A; Stolk, Leo M L; Neef, Cees; Bazelier, Marloes T

    2013-11-01

    Observational studies have shown conflicting results on the potential protecting effect of biguanide use with the risk of colorectal neoplasms. In addition, the cellular mechanism can either support or oppose biguanides influence on colorectal carcinoma. Our objective was to evaluate the association between biguanide use and colorectal carcinoma. A population-based cohort study using healthcare data from the Danish National database (1996-2007), was conducted. Oral antidiabetic drug users (n = 177,281) were matched 1:3 with a population-based reference group. Cox proportional hazard models estimated hazard ratios (HRs) of colorectal carcinoma. Stratification was performed to analyse the risk of colorectal cancer in current biguanide users. Two sub-analyses were performed, to investigate the risk of colorectal cancer associated with discontinuous and prolonged use of biguanides. Instead of a protective effect, we found that current biguanide users had a 1.2-fold increased risk of colorectal cancer (HR = 1.19, 95% CI = 1.08-1.30) as compared with the non-diabetes reference group. Prolonged use was not inversely associated with colorectal cancer either. When studying colorectal risk with biguanides, the underlying T2DM should be taken into account since a 1.3-1.6-fold increased risk was found in oral antidiabetic drug users compared to controls unexposed to diabetic medication. This study could not detect a protective effect of biguanide use with colorectal cancer. Therefore, this study does not support a further investigation of the effectiveness of biguanides to prevent colorectal carcinoma in clinical studies.

  15. Role of surgery for colorectal cancer in the elderly

    PubMed Central

    Biondi, Antonio; Vacante, Marco; Ambrosino, Immacolata; Cristaldi, Erika; Pietrapertosa, Giuseppe; Basile, Francesco

    2016-01-01

    The prevalence of subjects with colorectal cancer is expected to grow in the next future decades and surgery represents the most successful treatment modality for these patients. Anyway, currently elderly subjects undergo less elective surgical procedures than younger patients mainly due to the high rates of postoperative morbidity and mortality. Some authors suggest extensive surgery, including multistage procedures, as carried out in younger patients while others promote less aggressive surgery. In older patients, laparoscopic-assisted colectomy showed a number of advantages compared to conventional open surgery that include lower stress, higher rate of independency after surgery, quicker return to prior activities and a decrease in costs. The recent advances in chemotherapy and the introduction of new surgical procedures such as the endoluminal stenting, suggest the need for a revisitation of surgical practice patterns and the role of palliative surgery, mainly for patients with advanced disease. In this article, we discuss the current role of surgery for elderly patients with colorectal cancer. PMID:27721923

  16. Therapeutic options for peritoneal metastasis arising from colorectal cancer

    PubMed Central

    Glockzin, Gabriel; Schlitt, Hans J; Piso, Pompiliu

    2016-01-01

    Peritoneal metastasis is a common sign of advanced tumor stage, tumor progression or tumor recurrence in patients with colorectal cancer. Due to the improvement of systemic chemotherapy, the development of targeted therapy and the introduction of additive treatment options such as cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), the therapeutic approach to peritoneal metastatic colorectal cancer (pmCRC) has changed over recent decades, and patient survival has improved. Moreover, in contrast to palliative systemic chemotherapy or best supportive care, the inclusion of CRS and HIPEC as inherent components of a multidisciplinary treatment regimen provides a therapeutic approach with curative intent. Although CRS and HIPEC are increasingly accepted as the standard of care for selected patients and have become part of numerous national and international guidelines, the individual role, optimal timing and ideal sequence of the different systemic, local and surgical treatment options remains a matter of debate. Ongoing and future randomized controlled clinical trials may help clarify the impact of the different components, allow for further improvement of patient selection and support the standardization of oncologic treatment regimens for pmCRC. The addition of further therapeutic options such as neoadjuvant intraperitoneal chemotherapy or pressurized intraperitoneal aerosol chemotherapy, should be investigated to optimize therapeutic regimens and further improve the oncological outcome.

  17. Multi-class texture analysis in colorectal cancer histology

    NASA Astrophysics Data System (ADS)

    Kather, Jakob Nikolas; Weis, Cleo-Aron; Bianconi, Francesco; Melchers, Susanne M.; Schad, Lothar R.; Gaiser, Timo; Marx, Alexander; Zöllner, Frank Gerrit

    2016-06-01

    Automatic recognition of different tissue types in histological images is an essential part in the digital pathology toolbox. Texture analysis is commonly used to address this problem; mainly in the context of estimating the tumour/stroma ratio on histological samples. However, although histological images typically contain more than two tissue types, only few studies have addressed the multi-class problem. For colorectal cancer, one of the most prevalent tumour types, there are in fact no published results on multiclass texture separation. In this paper we present a new dataset of 5,000 histological images of human colorectal cancer including eight different types of tissue. We used this set to assess the classification performance of a wide range of texture descriptors and classifiers. As a result, we found an optimal classification strategy that markedly outperformed traditional methods, improving the state of the art for tumour-stroma separation from 96.9% to 98.6% accuracy and setting a new standard for multiclass tissue separation (87.4% accuracy for eight classes). We make our dataset of histological images publicly available under a Creative Commons license and encourage other researchers to use it as a benchmark for their studies.

  18. Gastrointestinal perforation due to bevacizumab in colorectal cancer.

    PubMed

    Saif, Muhammad Wasif; Elfiky, Aymen; Salem, Ronald R

    2007-06-01

    Bevacizumab is the first U.S. Food and Drug Association-approved vascular endothelial growth factor-targeted agent that greatly increases progression-free and overall survival in combination with standard chemotherapy regimens in patients with metastatic colorectal cancer. Although bevacizumab is generally well tolerated, some serious adverse events have occurred in some patients in clinical trials, including arterial thromboembolism and gastrointestinal (GI) perforation. GI perforation was first observed in the pivotal phase 3 trial, in which six events occurred in bevacizumab group (1.5%), compared with no events in the control group. Since then, similar rates of GI perforation have been observed in other large trials. Typical presentation was abdominal pain associated with constipation and vomiting. Such events occurred throughout treatment and were not correlated with duration of exposure. No difference in rate of GI perforations was found in patients who did and did not have a baseline history of peptic ulcer disease, diverticulosis, and history of chronic use of nonsteroidal anti-inflammatory drugs. However, the incidence of GI perforation seemed to be higher in patients with primary tumor intact, recent history of sigmoidoscopy or colonoscopy, or previous adjuvant radiotherapy, but it is necessary to confirm these preliminary findings by multivariate analyses. The mechanism responsible for causing GI perforation is not known and may be multifactorial. Bevacizumab should be permanently discontinued in patients who develop GI perforation. This article reviews the incidence, presentation, pathogenesis, risk factors, and management of GI perforation in patients with colorectal cancer who are treated with bevacizumab.

  19. Multi-class texture analysis in colorectal cancer histology

    PubMed Central

    Kather, Jakob Nikolas; Weis, Cleo-Aron; Bianconi, Francesco; Melchers, Susanne M.; Schad, Lothar R.; Gaiser, Timo; Marx, Alexander; Zöllner, Frank Gerrit

    2016-01-01

    Automatic recognition of different tissue types in histological images is an essential part in the digital pathology toolbox. Texture analysis is commonly used to address this problem; mainly in the context of estimating the tumour/stroma ratio on histological samples. However, although histological images typically contain more than two tissue types, only few studies have addressed the multi-class problem. For colorectal cancer, one of the most prevalent tumour types, there are in fact no published results on multiclass texture separation. In this paper we present a new dataset of 5,000 histological images of human colorectal cancer including eight different types of tissue. We used this set to assess the classification performance of a wide range of texture descriptors and classifiers. As a result, we found an optimal classification strategy that markedly outperformed traditional methods, improving the state of the art for tumour-stroma separation from 96.9% to 98.6% accuracy and setting a new standard for multiclass tissue separation (87.4% accuracy for eight classes). We make our dataset of histological images publicly available under a Creative Commons license and encourage other researchers to use it as a benchmark for their studies. PMID:27306927

  20. Therapeutic options for peritoneal metastasis arising from colorectal cancer.

    PubMed

    Glockzin, Gabriel; Schlitt, Hans J; Piso, Pompiliu

    2016-08-01

    Peritoneal metastasis is a common sign of advanced tumor stage, tumor progression or tumor recurrence in patients with colorectal cancer. Due to the improvement of systemic chemotherapy, the development of targeted therapy and the introduction of additive treatment options such as cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), the therapeutic approach to peritoneal metastatic colorectal cancer (pmCRC) has changed over recent decades, and patient survival has improved. Moreover, in contrast to palliative systemic chemotherapy or best supportive care, the inclusion of CRS and HIPEC as inherent components of a multidisciplinary treatment regimen provides a therapeutic approach with curative intent. Although CRS and HIPEC are increasingly accepted as the standard of care for selected patients and have become part of numerous national and international guidelines, the individual role, optimal timing and ideal sequence of the different systemic, local and surgical treatment options remains a matter of debate. Ongoing and future randomized controlled clinical trials may help clarify the impact of the different components, allow for further improvement of patient selection and support the standardization of oncologic treatment regimens for pmCRC. The addition of further therapeutic options such as neoadjuvant intraperitoneal chemotherapy or pressurized intraperitoneal aerosol chemotherapy, should be investigated to optimize therapeutic regimens and further improve the oncological outcome. PMID:27602235

  1. Therapeutic options for peritoneal metastasis arising from colorectal cancer

    PubMed Central

    Glockzin, Gabriel; Schlitt, Hans J; Piso, Pompiliu

    2016-01-01

    Peritoneal metastasis is a common sign of advanced tumor stage, tumor progression or tumor recurrence in patients with colorectal cancer. Due to the improvement of systemic chemotherapy, the development of targeted therapy and the introduction of additive treatment options such as cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), the therapeutic approach to peritoneal metastatic colorectal cancer (pmCRC) has changed over recent decades, and patient survival has improved. Moreover, in contrast to palliative systemic chemotherapy or best supportive care, the inclusion of CRS and HIPEC as inherent components of a multidisciplinary treatment regimen provides a therapeutic approach with curative intent. Although CRS and HIPEC are increasingly accepted as the standard of care for selected patients and have become part of numerous national and international guidelines, the individual role, optimal timing and ideal sequence of the different systemic, local and surgical treatment options remains a matter of debate. Ongoing and future randomized controlled clinical trials may help clarify the impact of the different components, allow for further improvement of patient selection and support the standardization of oncologic treatment regimens for pmCRC. The addition of further therapeutic options such as neoadjuvant intraperitoneal chemotherapy or pressurized intraperitoneal aerosol chemotherapy, should be investigated to optimize therapeutic regimens and further improve the oncological outcome. PMID:27602235

  2. Inflammation and colorectal cancer, when microbiota-host mutualism breaks

    PubMed Central

    Candela, Marco; Turroni, Silvia; Biagi, Elena; Carbonero, Franck; Rampelli, Simone; Fiorentini, Carla; Brigidi, Patrizia

    2014-01-01

    Structural changes in the gut microbial community have been shown to accompany the progressive development of colorectal cancer. In this review we discuss recent hypotheses on the mechanisms involved in the bacteria-mediated carcinogenesis, as well as the triggering factors favoring the shift of the gut microbiota from a mutualistic to a pro-carcinogenic configuration. The possible role of inflammation, bacterial toxins and toxic microbiota metabolites in colorectal cancer onset is specifically discussed. On the other hand, the strategic role of inflammation as the keystone factor in driving microbiota to become carcinogenic is suggested. As a common outcome of different environmental and endogenous triggers, such as diet, aging, pathogen infection or genetic predisposition, inflammation can compromise the microbiota-host mutualism, forcing the increase of pathobionts at the expense of health-promoting groups, and allowing the microbiota to acquire an overall pro-inflammatory configuration. Consolidating inflammation in the gut, and favoring the bloom of toxigenic bacterial drivers, these changes in the gut microbial ecosystem have been suggested as pivotal in promoting carcinogenesis. In this context, it will become of primary importance to implement dietary or probiotics-based interventions aimed at preserving the microbiota-host mutualism along aging, counteracting deviations that favor a pro-carcinogenic microbiota asset. PMID:24574765

  3. Extracellular HSP110 skews macrophage polarization in colorectal cancer.

    PubMed

    Berthenet, Kevin; Boudesco, Christophe; Collura, Ada; Svrcek, Magali; Richaud, Sarah; Hammann, Arlette; Causse, Sebastien; Yousfi, Nadhir; Wanherdrick, Kristell; Duplomb, Laurence; Duval, Alex; Garrido, Carmen; Jego, Gaetan

    2016-07-01

    HSP110 is induced by different stresses and, through its anti-apoptotic and chaperoning properties, helps the cells to survive these adverse situations. In colon cancers, HSP110 is abnormally abundant. We have recently showed that colorectal cancer (CRC) patients with microsatellite instability (MSI) had an improved response to chemotherapy because they harbor an HSP110 inactivating mutation (HSP110DE9). In this work, we have used patients' biopsies and human CRC cells grown in vitro and in vivo (xenografts) to demonstrate that (1) HSP110 is secreted by CRC cells and that the amount of this extracellular HSP110 is strongly decreased by the expression of the mutant HSP110DE9, (2) Supernatants from CRC cells overexpressing HSP110 or purified recombinant human HSP110 (LPS-free) affect macrophage differentiation/polarization by favoring a pro-tumor, anti-inflammatory profile, (3) Conversely, inhibition of HSP110 (expression of siRNA, HSP110DE9 or immunodepletion) induced the formation of macrophages with a cytotoxic, pro-inflammatory profile. (4) Finally, this effect of extracellular HSP110 on macrophages seems to implicate TLR4. These results together with the fact that colorectal tumor biopsies with HSP110 high were infiltrated with macrophages with a pro-tumoral profile while those with HSP110 low were infiltrated with macrophages with a cytotoxic profile, suggest that the effect of extracellular HSP110 function on macrophages may also contribute to the poor outcomes associated with HSP110 expression. PMID:27622020

  4. Trends in colorectal cancer mortality in Europe: retrospective analysis of the WHO mortality database

    PubMed Central

    Ait Ouakrim, Driss; Pizot, Cécile; Boniol, Magali; Malvezzi, Matteo; Boniol, Mathieu; Negri, Eva; Bota, Maria; Jenkins, Mark A; Bleiberg, Harry

    2015-01-01

    Objective To examine changes in colorectal cancer mortality in 34 European countries between 1970 and 2011. Design Retrospective trend analysis. Data source World Health Organization mortality database. Population Deaths from colorectal cancer between 1970 and 2011. Profound changes in screening and treatment efficiency took place after 1988; therefore, particular attention was paid to the evolution of colorectal cancer mortality in the subsequent period. Main outcomes measures Time trends in rates of colorectal cancer mortality, using joinpoint regression analysis. Rates were age adjusted using the standard European population. Results From 1989 to 2011, colorectal cancer mortality increased by a median of 6.0% for men and decreased by a median of 14.7% for women in the 34 European countries. Reductions in colorectal cancer mortality of more than 25% in men and 30% in women occurred in Austria, Switzerland, Germany, the United Kingdom, Belgium, the Czech Republic, Luxembourg, and Ireland. By contrast, mortality rates fell by less than 17% in the Netherlands and Sweden for both sexes. Over the same period, smaller or no declines occurred in most central European countries. Substantial mortality increases occurred in Croatia, the former Yugoslav republic of Macedonia, and Romania for both sexes and in most eastern European countries for men. In countries with decreasing mortality, reductions were more important for women of all ages and men younger than 65 years. In the 27 European Union member states, colorectal cancer mortality fell by 13.0% in men and 27.0% in women, compared with corresponding reductions of 39.8% and 38.8% in the United States. Conclusion Over the past 40 years, there has been considerable disparity in the level of colorectal cancer mortality between European countries, as well as between men and women and age categories. Countries with the largest reductions in colorectal cancer mortality are characterised by better accessibility to screening

  5. Biomolecular markers as determinants of patients selection for adjuvant chemotherapy of sporadic colorectal cancers.

    PubMed

    Sudoyo, Aru W

    2010-01-01

    Colorectal cancer (CRC) is a disease classified and based on genetic alteration resulting from interaction of environmental factors, individual cancer susceptibility and accumulated somatic changes of the colorectal epithelium. Advanced knowledge in genetics and epigenetics of colorectal cancer develops a hypothesis that various clinical manifestations of colorectal cancer are caused by different carcinogenesis pathways. Different carcinogenesis pathways and types of colorectal cancer appear to bring effects on different response against chemotherapy and prognosis. Chemotherapy is mainly provided for patients with stage III CRC which are also the largest proportion of CRC patients in Indonesia. However, it is also provided for some patients with high risk stage II CRC. Classically, clinical factors have been generally accepted as prognostic factors including depth of tumor invasion, regional nodal metastasis, vascular invasion, poor differentiation, and serologic tumor marker such as carcinoembryonic antigen (CEA). However, clinical and histopathological factors themselves do not provide accurate prediction for colorectal cancer prognosis and treatment. A biomolecular marker is necessary to provide such prediction. Numerous studies have been conducted to evaluate the molecular biological markers in order to determine either the possibility of successful treatment for colorectal cancer (predictive factor) or life-expectancy (prognostic factor). Results of several studies demonstrate different status of some molecular markers to determine successful treatment between stage II and stage III colorectal cancer. Certainly, such finding should be followed up but it shall be accepted that there will be a shift of paradigm of CRC treatment. Therefore, the success of colorectal cancer, excluding the patient's socioeconomic factors and the surgeon's skill, will depend extremely on molecular parameter and not only the stage.

  6. STAT3: An Anti-Invasive Factor in Colorectal Cancer?

    PubMed Central

    de Jong, Petrus Rudolf; Mo, Ji-Hun; Harris, Alexandra R.; Lee, Jongdae; Raz, Eyal

    2014-01-01

    Signal Transducer and Activator of Transcription 3 (STAT3) is activated in a majority of cancers, and promotes tumorigenesis and even metastasis through transcriptional activation of its target genes. Recently, we discovered that STAT3 suppresses epithelial-to-mesenchymal transition (EMT) and thus metastasis in a mouse model of colorectal cancer (CRC), while it did not affect the overall tumor burden. Furthermore, we found that STAT3 in intestinal epithelial cells (IEC) suppresses EMT by regulating stability of an EMT inducer, SNAI-1 (Snail-1). Here, STAT3 functions as an adaptor rather than a transcription factor in the post-translational modification of SNAI-1. In this review, we discuss the unexpected and contradictory role of STAT3 in metastasis of CRC and its clinical implications. PMID:24995503

  7. Immunotherapy in human colorectal cancer: Challenges and prospective

    PubMed Central

    Sun, Xuan; Suo, Jian; Yan, Jun

    2016-01-01

    Human colorectal cancer (CRC) is the third most commonly diagnosed malignancies and the prognosis for patients with recurrent or metastatic disease is extremely poor. Although new chemotherapeutic regimen improves survival rates, therapy with better efficacy and less adverse effects is drastically needed. Immunotherapy has been investigated in human CRC for decades with limited success. However, recent developments of immunotherapy, particularly immune checkpoint inhibitor therapy, have achieved promising clinical benefits in many types of cancer and revived the hope for utilizing such therapy in human CRC. In this review, we will discuss important immunological landscape within the CRC microenvironment and introduce immunoscore system to better describe immunophenotyping in CRC. We will also discuss different immunotherapeutic approaches currently utilized in different phases of clinical trials. Some of those completed or ongoing trials are summarized. Finally, we provide a brief prospective on the future human CRC immunotherapy.

  8. Metastatic Colorectal Cancer Resembling Severe Preeclampsia in Pregnancy

    PubMed Central

    Khangura, Raminder Kaur; Khangura, Charanpreet Kaur; Desai, Anagha; Goyert, Gregory; Sangha, Roopina

    2015-01-01

    Although colorectal cancer (CRC) is the third most common cancer in women, it is a rare malignancy in pregnancy. Symptoms of CRC such as fatigue, malaise, nausea, vomiting, rectal bleeding, anemia, altered bowel habits, and abdominal mass are often considered typical symptoms of pregnancy. Many cases of CRC are diagnosed in advanced stages due to missed warning signs of CRC, which may be misinterpreted as normal symptoms related to pregnancy. This report reviews 2 cases of CRC diagnosed within a 4-month interval at our institution. Both cases were initially thought to be atypical presentations of preeclampsia. Prenatal history, hospital course, and postpartum course were reviewed for both patients. CRC is often diagnosed at advanced stages in pregnancy. Common physiological symptoms of pregnancy should be scrutinized carefully and worked up appropriately, especially if symptoms remain persistent or increase in intensity or severity. PMID:26770850

  9. [Multi-Line Chemotherapy for Metastatic Colorectal Cancer].

    PubMed

    Terakura, Masanobu; Mayumi, Katsuyuki; Takemura, Masashi

    2016-09-01

    We administered multi-line chemotherapy(ie, more than fifth-line chemotherapy)to 5 patients with metastatic colorectal cancer(age range, 62to 78 years; median age, 68years). Four of the five patients died because of cancer progression; however, the mean overall survival(OS)was 39 months. In our experience, re-challenging with key drugs was associated with clinical benefits. A case that could be thrown until ninth-line treatment was also experienced. A strategy based on rechallenging and changes in the combination of key drugs[5-FU-based chemotherapy, oxaliplatin, irinotecan(CPT-11), bevacizumab(Bmab)and panitumumab(Pmab)]may prolong life and offer new hope for these patients. PMID:27628558

  10. Regulatory Roles of Non-Coding RNAs in Colorectal Cancer.

    PubMed

    Wang, Jun; Song, Yong-Xi; Ma, Bin; Wang, Jia-Jun; Sun, Jing-Xu; Chen, Xiao-Wan; Zhao, Jun-Hua; Yang, Yu-Chong; Wang, Zhen-Ning

    2015-08-21

    Non-coding RNAs (ncRNAs) have recently gained attention because of their involvement in different biological processes. An increasing number of studies have demonstrated that mutations or abnormal expression of ncRNAs are closely associated with various diseases including cancer. The present review is a comprehensive examination of the aberrant regulation of ncRNAs in colorectal cancer (CRC) and a summary of the current findings on ncRNAs, including long ncRNAs, microRNAs, small interfering RNAs, small nucleolar RNAs, small nuclear RNAs, Piwi-interacting RNAs, and circular RNAs. These ncRNAs might become novel biomarkers and targets as well as potential therapeutic tools for the treatment of CRC in the near future and this review may provide important clues for further research on CRC and for the selection of effective therapeutic targets.

  11. Genetic mapping of a locus predisposing to human colorectal cancer

    SciTech Connect

    Peltomaeki, P.; Aaltonen, L.A.; Pylkkaenen, L.; Chappelle, A. de la ); Sistonen, P. Finnish Red Cross Blood Transfusion Service, Helsinki ); Mecklin, J.P. ); Haervinen, H. ); Green, J.S. ); Jass, J.R. ); Weber, J.L. ); Leach, F.S.; Petersen, G.M.; Hamilton, S.R.; Vogelstein, B. Johns Hopkins Hospital, Baltimore, MD )

    1993-05-07

    Genetic linkage analysis was used to determine whether a specific chromosomal locus could be implicated in families with a history of early onset cancer but with no other unique features. Close linkage of disease to anonymous microsatellite markers on chromosome 2 was demonstrated in two large kindreds. The pairwise lod scores for linkage to marker D2S123 in these kindreds were 6.39 and 1.45 at zero recombination, and multipoint linkage with flanking markers resulted in lod scores of 6.47 and 6.01. These results prove the existence of a genetically determined predisposition to colorectal cancer that has important ramifications for understanding and preventing this disease. 13 refs., 1 fig., 1 tab.

  12. Colorectal cancer screening brochure for Latinos: focus group evaluation.

    PubMed

    Cooperman, Julia L; Efuni, Elizaveta; Villagra, Cristina; DuHamel, Katherine; Jandorf, Lina

    2013-09-01

    Colorectal cancer (CRC) can be effectively prevented via screening colonoscopy, yet adherence rates remain low among Latinos. Interventions targeting individual and cultural barriers to screening are needed. We developed an educational brochure to target these barriers faced by a diverse Latino population. The objective was to evaluate the responses of the target population to the culturally and theoretically informed brochure through community member focus groups. Facilitators conducted six focus groups, stratified by gender, language, and prior colonoscopy experience. Topics included: brochure content and layout, cancer knowledge, and CRC screening determinants. Focus groups documented community members' responses to the brochure's overall message and its informational and visual components. Changes to wording, visual aids, and content were suggested to make the brochure culturally more acceptable. Results indicated relevance of the theoretically and culturally guided approach to the development of the brochure leading to refinement of its content and design.

  13. Immunotherapy in human colorectal cancer: Challenges and prospective

    PubMed Central

    Sun, Xuan; Suo, Jian; Yan, Jun

    2016-01-01

    Human colorectal cancer (CRC) is the third most commonly diagnosed malignancies and the prognosis for patients with recurrent or metastatic disease is extremely poor. Although new chemotherapeutic regimen improves survival rates, therapy with better efficacy and less adverse effects is drastically needed. Immunotherapy has been investigated in human CRC for decades with limited success. However, recent developments of immunotherapy, particularly immune checkpoint inhibitor therapy, have achieved promising clinical benefits in many types of cancer and revived the hope for utilizing such therapy in human CRC. In this review, we will discuss important immunological landscape within the CRC microenvironment and introduce immunoscore system to better describe immunophenotyping in CRC. We will also discuss different immunotherapeutic approaches currently utilized in different phases of clinical trials. Some of those completed or ongoing trials are summarized. Finally, we provide a brief prospective on the future human CRC immunotherapy. PMID:27605872

  14. Colorectal cancer care in elderly patients: Unsolved issues.

    PubMed

    Aparicio, Thomas; Pamoukdjian, Frederic; Quero, Laurent; Manfredi, Sylvain; Wind, Philippe; Paillaud, Elena

    2016-10-01

    Colorectal cancers are common in elderly patients. However, cancer screening is poorly used after 75. Elderly patients form a heterogeneous population with specific characteristics. Standards of care cannot therefore be transposed from young to elderly patients. Tumour resection is frequently performed but adjuvant chemotherapy is rarely prescribed as there are no clearly established standards of care. In a metastatic setting, recent phase III studies have demonstrated that doublet front-line chemotherapy provided no survival benefit. Moreover, several studies have established the benefit of bevacizumab in association with chemotherapy. There is a lack of evidence for the efficacy of anti-epidermal growth factor antibodies in elderly patients. Geriatric assessments could help to select the adequate treatment strategy for individual patients. Geriatric oncology is now the challenge we have to face, and more specific trials are needed.

  15. Immunotherapy in human colorectal cancer: Challenges and prospective.

    PubMed

    Sun, Xuan; Suo, Jian; Yan, Jun

    2016-07-28

    Human colorectal cancer (CRC) is the third most commonly diagnosed malignancies and the prognosis for patients with recurrent or metastatic disease is extremely poor. Although new chemotherapeutic regimen improves survival rates, therapy with better efficacy and less adverse effects is drastically needed. Immunotherapy has been investigated in human CRC for decades with limited success. However, recent developments of immunotherapy, particularly immune checkpoint inhibitor therapy, have achieved promising clinical benefits in many types of cancer and revived the hope for utilizing such therapy in human CRC. In this review, we will discuss important immunological landscape within the CRC microenvironment and introduce immunoscore system to better describe immunophenotyping in CRC. We will also discuss different immunotherapeutic approaches currently utilized in different phases of clinical trials. Some of those completed or ongoing trials are summarized. Finally, we provide a brief prospective on the future human CRC immunotherapy. PMID:27605872

  16. Regulatory Roles of Non-Coding RNAs in Colorectal Cancer

    PubMed Central

    Wang, Jun; Song, Yong-Xi; Ma, Bin; Wang, Jia-Jun; Sun, Jing-Xu; Chen, Xiao-Wan; Zhao, Jun-Hua; Yang, Yu-Chong; Wang, Zhen-Ning

    2015-01-01

    Non-coding RNAs (ncRNAs) have recently gained attention because of their involvement in different biological processes. An increasing number of studies have demonstrated that mutations or abnormal expression of ncRNAs are closely associated with various diseases including cancer. The present review is a comprehensive examination of the aberrant regulation of ncRNAs in colorectal cancer (CRC) and a summary of the current findings on ncRNAs, including long ncRNAs, microRNAs, small interfering RNAs, small nucleolar RNAs, small nuclear RNAs, Piwi-interacting RNAs, and circular RNAs. These ncRNAs might become novel biomarkers and targets as well as potential therapeutic tools for the treatment of CRC in the near future and this review may provide important clues for further research on CRC and for the selection of effective therapeutic targets. PMID:26307974

  17. Prognostic significance of CD168 overexpression in colorectal cancer

    PubMed Central

    Wang, Ke; Zhang, Tao

    2016-01-01

    The expression of cluster of differentiation 168 (CD168), a cell surface receptor for hyaluronan, is associated with cancer progression and metastases. The aim of the present study was to analyze the expression of CD168 by immunohistochemistry in colorectal cancer (CRC) and to examine the association between CD168 expression and clinicopathological features, including survival. A total of 78 tissue specimens obtained from consecutive CRC patients exhibiting various tumor node metastasis (TNM) stages were immunostained for the analysis of CD168 expression. The prognostic value of CD168 was subsequently evaluated. Kaplan-Meier survival analysis revealed that CD168 overexpression was significantly associated with overall survival (P<0.05); however, no significant association was identified between CD168 expression and tumor location, tumor differentiation or TNM stage. Overexpression of CD168 was closely associated with poorer patient survival, which indicates that it may present a useful indicator for clinical prognosis.

  18. Pharmacogenomics in colorectal cancer: The first step for individualized-therapy

    PubMed Central