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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

    ... Hindi (हिन्दी) Japanese (日本語) Korean (한국어) Portuguese (português) Russian (Русский) Somali (af Soomaali) Spanish (español) Tagalog ( ... 한국어 (Korean) Bilingual PDF Health Information Translations Portuguese (português) Cancer of the Colon and Rectum Câncer do ...

  3. Colorectal Cancer - Multiple Languages: MedlinePlus

    MedlinePlus

    ... sharing features on this page, please enable JavaScript. Arabic (العربية) Bosnian (Bosanski) Chinese - Simplified (简体中文) Chinese - Traditional ( ... Soomaali) Spanish (español) Tagalog (Tagalog) Vietnamese (Tiếng Việt) Arabic (العربية) Cancer of the Colon and Rectum (Arabic) ...

  4. 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 ...

  5. Colorectal Cancer

    MedlinePlus

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

  6. Aberrant Gene Promoter Methylation Associated with Sporadic Multiple Colorectal Cancer

    PubMed Central

    Gonzalo, Victoria; Lozano, Juan José; Muñoz, Jenifer; Balaguer, Francesc; Pellisé, Maria; de Miguel, Cristina Rodríguez; Andreu, Montserrat; Jover, Rodrigo; Llor, Xavier; Giráldez, M. Dolores; Ocaña, Teresa; Serradesanferm, Anna; Alonso-Espinaco, Virginia; Jimeno, Mireya; Cuatrecasas, Miriam; Sendino, Oriol; Castellví-Bel, Sergi; Castells, Antoni

    2010-01-01

    Background Colorectal cancer (CRC) multiplicity has been mainly related to polyposis and non-polyposis hereditary syndromes. In sporadic CRC, aberrant gene promoter methylation has been shown to play a key role in carcinogenesis, although little is known about its involvement in multiplicity. To assess the effect of methylation in tumor multiplicity in sporadic CRC, hypermethylation of key tumor suppressor genes was evaluated in patients with both multiple and solitary tumors, as a proof-of-concept of an underlying epigenetic defect. Methodology/Principal Findings We examined a total of 47 synchronous/metachronous primary CRC from 41 patients, and 41 gender, age (5-year intervals) and tumor location-paired patients with solitary tumors. Exclusion criteria were polyposis syndromes, Lynch syndrome and inflammatory bowel disease. DNA methylation at the promoter region of the MGMT, CDKN2A, SFRP1, TMEFF2, HS3ST2 (3OST2), RASSF1A and GATA4 genes was evaluated by quantitative methylation specific PCR in both tumor and corresponding normal appearing colorectal mucosa samples. Overall, patients with multiple lesions exhibited a higher degree of methylation in tumor samples than those with solitary tumors regarding all evaluated genes. After adjusting for age and gender, binomial logistic regression analysis identified methylation of MGMT2 (OR, 1.48; 95% CI, 1.10 to 1.97; p = 0.008) and RASSF1A (OR, 2.04; 95% CI, 1.01 to 4.13; p = 0.047) as variables independently associated with tumor multiplicity, being the risk related to methylation of any of these two genes 4.57 (95% CI, 1.53 to 13.61; p = 0.006). Moreover, in six patients in whom both tumors were available, we found a correlation in the methylation levels of MGMT2 (r = 0.64, p = 0.17), SFRP1 (r = 0.83, 0.06), HPP1 (r = 0.64, p = 0.17), 3OST2 (r = 0.83, p = 0.06) and GATA4 (r = 0.6, p = 0.24). Methylation in normal appearing colorectal mucosa from patients with multiple

  7. 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

  8. Multiple sporadic colorectal cancers display a unique methylation phenotype.

    PubMed

    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

  9. 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

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

    PubMed

    Cheng, Timothy H T; Gorman, Maggie; Martin, Lynn; Barclay, Ella; Casey, Graham; Saunders, Brian; Thomas, Huw; Clark, Sue; Tomlinson, Ian

    2015-02-01

    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

  11. 6 Common Cancers - Colorectal Cancer

    MedlinePlus

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

  12. 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 ( ...

  13. 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- ...

  14. 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 ...

  15. Deriving stage at diagnosis from multiple population-based sources: colorectal and lung cancer in England

    PubMed Central

    Benitez-Majano, S; Fowler, H; Maringe, C; Di Girolamo, C; Rachet, B

    2016-01-01

    Background: Stage at diagnosis is a strong predictor of cancer survival. Differences in stage distributions and stage-specific management help explain geographic differences in cancer outcomes. Stage information is thus essential to improve policies for cancer control. Despite recent progress, stage information is often incomplete. Data collection methods and definition of stage categories are rarely reported. These inconsistencies may result in assigning conflicting stage for single tumours and confound the interpretation of international comparisons and temporal trends of stage-specific cancer outcomes. We propose an algorithm that uses multiple routine, population-based data sources to obtain the most complete and reliable stage information possible. Methods: Our hierarchical approach derives a single stage category per tumour prioritising information deemed of best quality from multiple data sets and various individual components of tumour stage. It incorporates rules from the Union for International Cancer Control TNM classification of malignant tumours. The algorithm is illustrated for colorectal and lung cancer in England. We linked the cancer-specific Clinical Audit data (collected from clinical multi-disciplinary teams) to national cancer registry data. We prioritise stage variables from the Clinical Audit and added information from the registry when needed. We compared stage distribution and stage-specific net survival using two sets of definitions of summary stage with contrasting levels of assumptions for dealing with missing individual TNM components. This exercise extends a previous algorithm we developed for international comparisons of stage-specific survival. Results: Between 2008 and 2012, 163 915 primary colorectal cancer cases and 168 158 primary lung cancer cases were diagnosed in adults in England. Using the most restrictive definition of summary stage (valid information on all individual TNM components), colorectal cancer stage

  16. What Is Colorectal Cancer?

    MedlinePlus

    ... on staging, see “ Colorectal cancer stages ” The normal colon and rectum The colon and rectum are parts ... through the anus . Types of cancer in the colon and rectum Adenocarcinomas make up more than 95% ...

  17. [Epidemiology of colorectal cancer].

    PubMed

    Bouvier, Anne-Marie; Launoy, Guy

    2015-06-01

    The incidence of colorectal cancer increased in France until the 2000s' then decreased. Time trends in incidence for this cancer varied according to its sublocation along the gut. Incidence increased for right and left colon cancers, whereas it remained stable for sigmoid cancers in males and decreased in females. Incidence decreased over time for rectal cancers. The proportion of colorectal cancer in the overall French cancer prevalence is 12%. In 2008, 121,000 patients had a colorectal cancer diagnosed in the 5 previous years. The cumulative risk of colorectal cancer increased from 3.9% for males born around 1900 to 4.9% for those born around 1930 and then slightly decreased, being 4.5% among those born around 1950. It remained at the same level for females and was 2.9% for those born around 1950. The prognosis of colorectal cancer improved over time. Net 5-year survival increased in males from 53% for cancers diagnosed between 1989 and 1991 to 58% for those diagnosed between 2001 and 2004. The highest improvement of 10 year survival rates concerned left colon and rectosigmoid junction (+19% in a decade). The progressive set up of national colorectal screening since the early 2000's and the introduction of recent immunological tests in 2015 should decrease the mortality for this cancer and, at term, should decrease its incidence too. PMID:26298897

  18. 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

  19. Epidemiology of colorectal cancer.

    PubMed

    Boyle, Peter; Leon, Maria Elena

    2002-01-01

    Colorectal cancer is a important public health problem: there are nearly one million new cases of colorectal cancer diagnosed world-wide each year and half a million deaths. Recent reports show that, in the US, it was the most frequent form of cancer among persons aged 75 years and older. Given that the majority of cancers occur in elder people and with the ageing of the population in mind, this observation gives further impetus to investigating prevention and treatment strategies among this subgroup of the population. Screening research, recommendations and implementation is an obvious priority. While there are many questions to be resolved, it is apparent that many facets of colorectal cancer are becoming increasingly understood and prospects for prevention are becoming apparent. Achieving colorectal cancer control is the immediate challenge. PMID:12421722

  20. Developments in Colorectal Cancer Screening

    MedlinePlus

    ... on. Feature: Colorectal Cancer Developments in Colorectal Cancer Screening Summer 2016 Table of Contents Dr. Asad Umar, ... know to help determine the best colon cancer screening test for them? Colonoscopy is considered the gold ...

  1. 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- ...

  2. 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

  3. 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 ...

  4. Screening for colorectal cancer.

    PubMed

    He, Jin; Efron, Jonathan E

    2011-01-01

    March is national colorectal cancer awareness month. It is estimated that as many as 60% of colorectal cancer deaths could be prevented if all men and women aged 50 years or older were screened routinely. In 2000, Katie Couric's televised colonoscopy led to a 20% increase in screening colonoscopies across America, a stunning rise called the "Katie Couric Effect". This event demonstrated how celebrity endorsement affects health behavior. Currently, discussion is ongoing about the optimal strategy for CRC screening, particularly the costs of screening colonoscopy. The current CRC screening guidelines are summarized in Table 2. Debates over the optimum CRC screening test continue in the face of evidence that 22 million Americans aged 50 to 75 years are not screened for CRC by any modality and 25,000 of those lives may have been saved if they had been screened for CRC. It is clear that improving screening rates and reducing disparities in underscreened communities and population subgroups could further reduce colorectal cancer morbidity and mortality. National Institutes of Health consensus identified the following priority areas to enhance the use and quality of colorectal cancer screening: Eliminate financial barriers to colorectal cancer screening and appropriate follow-up of positive results of colorectal cancer screening. Develop systems to ensure the high quality of colorectal cancer screening programs. Conduct studies to determine the comparative effectiveness of the various colorectal cancer screening methods in usual practice settings. Encouraging population adherence to screening tests and allowing patients to select the tests they prefer may do more good (as long as they choose something) than whatever procedure is chosen by the medical profession as the preferred test. PMID:21954677

  5. Colorectal cancer in adolescents.

    PubMed Central

    Shankar, A.; Renaut, A. J.; Whelan, J.; Taylor, I.

    1999-01-01

    Colorectal cancer, one of the most common malignancies among adults, is rare in adolescence. This low incidence coupled with non-specific symptoms and aggressive natural history leads to a poorer prognosis than in reported adult series. This article describes two cases of colorectal cancer in adolescents and reviews the literature regarding this rare condition. Earlier diagnosis and a greater understanding of the natural history may lead to improved treatment with concomitant improvements in survival. Images Figure 1 Figure 2 PMID:10364965

  6. Screening for colorectal cancer.

    PubMed Central

    Campbell, W. J.; Moorehead, R. J.

    1997-01-01

    Colorectal carcinoma represents a major cause of cancer deaths in the United Kingdom. Tumours detected at an early or even premalignant stage have a better prognosis. In this review we consider the argument for screening for colorectal carcinomas and discuss the means available and the implications of implementing screening programmes using some of these methods. A suggestion is made for the more rational use of limited resources to target those at greatest risk. PMID:9185482

  7. Significant Evidence of Linkage for a Gene Predisposing to Colorectal Cancer and Multiple Primary Cancers on 22q11

    PubMed Central

    Teerlink, Craig; Nelson, Quentin; Burt, Randall; Cannon-Albright, Lisa

    2014-01-01

    Objectives: The genetic basis of colorectal cancer (CRC) is not completely specified. Part of the difficulty in mapping predisposition genes for CRC may be because of phenotypic heterogeneity. Using data from a population genealogy of Utah record linked to a statewide cancer registry, we identified a subset of CRC cases that exhibited familial clustering in excess of that expected for all CRC cases in general, which may represent a genetically homogeneous subset of CRC. Methods: Using a new familial aggregation method referred to as the subset genealogic index of familiality (subsetGIF), combined with detailed information from a statewide tumor registry, we identified a subset of CRC cases that exhibited excess familial clustering above that expected for CRC: CRC cases who had at least one other primary tumor at a different site. A genome-wide linkage analysis was performed on a set of high-risk CRC pedigrees that included multiple CRC cases with additional primaries to identify evidence for predisposition loci. Results: A total of 13 high-risk CRC pedigrees with multiple CRC cases with other primary cancers were identified. Linkage analysis identified one pedigree with a significant linkage signal at 22q11 (LOD (logarithm (base 10) of odds)=3.39). Conclusions: A predisposition gene or variant for CRC that also predisposes to other primary cancers likely resides on chromosome 22q11. The ability to use statewide population genealogy and tumor registry data was critical to identify an informative subset of CRC cases that is possibly more genetically homogeneous than CRC in general, and may have improved statistical power for predisposition locus identification in this study. PMID:24572700

  8. Get Tested for Colorectal Cancer

    MedlinePlus

    ... section Colorectal Cancer 4 of 6 sections Take Action! Take Action: Get Tested The best way to prevent colorectal ... I at Risk? 5 of 6 sections Take Action: Healthy Habits Quit smoking. People who smoke are ...

  9. Endobronchial metastases of colorectal cancer.

    PubMed

    Rosado Dawid, Natalia-Zuberoa; Villegas Fernández, Francisco Ramón; Rodríguez Cruz, María Del Mar; Ramos Meca, Asunción

    2016-04-01

    Colorectal metastases affecting trachea or bronchi are highly unusual. Up to 26% of endotracheal/endobronchial metastases are due to colorectal cancer. Treatment and palliative management rely on a multidisciplinary team to improve their quality of life. PMID:26856850

  10. [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

  11. 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

  12. 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.

  13. Worldwide variations in colorectal cancer.

    PubMed

    Center, Melissa M; Jemal, Ahmedin; Smith, Robert A; Ward, Elizabeth

    2009-01-01

    Previous studies have documented significant international variations in colorectal cancer rates. However, these studies were limited because they were based on old data or examined only incidence or mortality data. In this article, the colorectal cancer burden and patterns worldwide are described using the most recently updated cancer incidence and mortality data available from the International Agency for Research on Cancer (IARC). The authors provide 5-year (1998-2002), age-standardized colorectal cancer incidence rates for select cancer registries in IARC's Cancer Incidence in Five Continents, and trends in age-standardized death rates by single calendar year for select countries in the World Health Organization mortality database. In addition, available information regarding worldwide colorectal cancer screening initiatives are presented. The highest colorectal cancer incidence rates in 1998-2002 were observed in registries from North America, Oceania, and Europe, including Eastern European countries. These high rates are most likely the result of increases in risk factors associated with "Westernization," such as obesity and physical inactivity. In contrast, the lowest colorectal cancer incidence rates were observed from registries in Asia, Africa, and South America. Colorectal cancer mortality rates have declined in many longstanding as well as newly economically developed countries; however, they continue to increase in some low-resource countries of South America and Eastern Europe. Various screening options for colorectal cancer are available and further international consideration of targeted screening programs and/or recommendations could help alleviate the burden of colorectal cancer worldwide. PMID:19897840

  14. 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

  15. [Epigenetics and colorectal cancer].

    PubMed

    Menéndez, Pablo; Villarejo, Pedro; Padilla, David; Menéndez, José María; Rodríguez Montes, José Antonio

    2012-05-01

    The epigenetic and physiological mechanisms that alter the structure of chromatin include the methylation of DNA, changes in the histones, and changes in RNA. A literature review has been carried out using PubMed on the evidence published on the association between epigenetics and colorectal cancer. The scientific literature shows that epigenetic changes, such as genetic modifications may be very significant in the origin of neoplastic disease, contributing both to the development and progression of the disease. PMID:22425513

  16. 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

  17. Familial colorectal cancer.

    PubMed

    Lung, M S; Trainer, A H; Campbell, I; Lipton, L

    2015-05-01

    Identifying individuals with a genetic predisposition to developing familial colorectal cancer (CRC) is crucial to the management of the affected individual and their family. In order to do so, the physician requires an understanding of the different gene mutations and clinical manifestations of familial CRC. This review summarises the genetics, clinical manifestations and management of the known familial CRC syndromes, specifically Lynch syndrome, familial adenomatous polyposis, MUTYH-associated neoplasia, juvenile polyposis syndrome and Peutz-Jeghers syndrome. An individual suspected of having a familial CRC with an underlying genetic predisposition should be referred to a familial cancer centre to enable pre-test counselling and appropriate follow up. PMID:25955461

  18. [Colorectal cancer screening].

    PubMed

    Castells, Antoni

    2013-10-01

    Colorectal cancer is the paradigm of tumoral growth that is susceptible to preventive measures, especially screening. Various screening strategies with demonstrated efficacy and efficiency are currently available, notable examples being the fecal occult blood test and endoscopic tests. In addition, new modalities have appeared in the last few years that could become viable alternatives in the near future. The present article reviews the most important presentations on colorectal screening at the annual congress of the American Gastroenterological Association held in Orlando in May 2013, with special emphasis on the medium- and long-term results of strategies using the fecal occult blood test and flexible sigmoidoscopy, as well as initial experiences with the use of new biomarkers. PMID:24160954

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. Xenovaccinotherapy for colorectal cancer.

    PubMed

    Seledtsov, Victor I; Niza, Natalya A; Felde, Mariya A; Shishkov, Alexey A; Samarin, Denis M; Seledtsova, Galina V; Seledtsov, Dmitriy V

    2007-01-01

    The objectives of this phase I-II trial were to assess the toxicity, immunological and clinical responses induced in 37 patients with stage IV colorectal cancer by the subcutaneous administration of a xenogenic polyantigenic vaccine (XPV) prepared from disrupted murine melanoma (B16) and carcinoma (LLC) cells. An inducing course of vaccinotherapy consisted of 10 immunizations (5 at weekly and 5 at fortnight intervals). Twenty-four hours later each of first 5 vaccinations the patient was subcutaneously given a low dose of the recombinant interleukin-2 (IL-2). A consolidating course of vaccinotherapy consisted of monthly vaccinations. No grade III or IV toxicities, but also laboratory and clinical signs of developing systemic autoimmune disorders were noted in any XPV-treated patient. A significant increase in cell-mediated immunoreactivity to both LLC and B16 antigens (Ags) occurred in the patients after inducing vaccinations, as determined by delayed-type hypersensitivity (DTH) skin reactions, as well as by blood lymphocyte proliferation responses. Vaccinations also led to increased cell-mediated reactivity to murine non-tumor, spleen cell (SC)-associated Ags. This reactivity, however, was not as significant as that to tumor-associated antigens (TAAs). XPV was also found to capable of generating IgG antibody-mediated responses. With immunotherapy concentrations of both interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) detectably elevated in patients' sera, suggesting intensification of T helper 1-/T helper 2-mediated responses in the XPV-treated patients. The average survival of the XPV-treated patients was noticeably superior than was that of the clinically comparable control patients (17 vs 7 months). Collectively the results suggest that xenogenic TAAs are safe to use, able to induce measurable cellular and humoral immune responses, and may be clinically effective in certain colorectal cancer patients. PMID:17258887

  5. Molecular genetics of colorectal cancer.

    PubMed

    Bogaert, Julie; Prenen, Hans

    2014-01-01

    Approximately 90% of colorectal cancer cases are sporadic without family history or genetic predisposition, while in less than 10% a causative genetic event has been identified. Historically, colorectal cancer classification was only based on clinical and pathological features. Many efforts have been made to discover the genetic and molecular features of colorectal cancer, and there is more and more evidence that these features determine the prognosis and response to (targeted) treatment. Colorectal cancer is a heterogeneous disease, with three known major molecular groups. The most common is the chromosomal instable group, characterized by an accumulation of mutations in specific oncogenes and tumor suppressor genes. The second is the microsatellite instable group, caused by dysfunction of DNA mismatch repair genes leading to genetic hypermutability. The CpG Island Methylation phenotype is the third group, distinguished by hypermethylation. Colorectal cancer subtyping has also been addressed using genome-wide gene expression profiling in large patient cohorts and recently several molecular classification systems have been proposed. In this review we would like to provide an up-to-date overview of the genetic aspects of colorectal cancer. PMID:24714764

  6. [Tumor markers for colorectal cancer].

    PubMed

    Yamamoto, H; Miyake, Y; Noura, S; Ogawa, M; Yasui, M; Ikenaga, M; Sekimoto, M; Monden, M

    2001-09-01

    CEA and CA19-9 are the two most common tumor markers for colorectal cancer that are currently utilized clinically. The positive rate of CEA is 40-60% and that of CA19-9 is 30-50%. Simultaneous use of the two markers is useful in evaluating the therapeutic effect and monitoring the recurrence of advanced colorectal cancer. Surgical specimens may also provide useful information for the appropriate treatment of patients. Using surgically resected lymph nodes, we examined micrometastasis to assess the spread of the cancer cells and the malignant potential of colorectal cancer. Immunohistochemical analysis using anti-cytokeratin antibody revealed no significant impact of micrometastasis on patient prognosis, while RT-PCR assay using CEA as a genetic marker suggested a positive value in predicting a rapid recurrence. Among various molecular markers, we found that CDC25B phosphatase was a powerful prognostic factor for colorectal cancer. Diagnosis of the existence and malignant potential of cancer cells, together with serum tumor marker levels, may help to construct a more useful system for the better treatment of colorectal cancer. PMID:11579645

  7. 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

  8. Alterations in K-ras, APC and p53-multiple genetic pathway in colorectal cancer among Indians.

    PubMed

    Malhotra, Pooja; Anwar, Mumtaz; Nanda, Neha; Kochhar, Rakesh; Wig, Jai Dev; Vaiphei, Kim; Mahmood, Safrun

    2013-06-01

    The incidence of colorectal cancer (CRC) is increasing rapidly in Asian countries during the past few decades, but no comprehensive analysis has been done to find out the exact cause of this disease. In this study, we investigated the frequencies of mutations and expression pattern of K-ras, APC (adenomatosis polyposis coli) and p53 in tumor, adjoining and distant normal mucosa and to correlate these alterations with patients clinicopathological parameters as well as with the survival. Polymerase chain reaction (PCR)-restriction digestion was used to detect mutations in K-ras and PCR-SSCP (Single Strand Conformation Polymorphism) followed by DNA sequencing was used to detect mutations in APC and p53 genes. Immunohistochemistry was used to detect the expression pattern of K-ras, APC and p53 proteins. The frequencies of mutations of K-ras, APC and p53 in 30 tumor tissues samples were 26.7 %, 46.7 % and 20 %, respectively. Only 3.3 % of tumors contained mutations in all the three genes. The most common combination of mutation was APC and p53 whereas mutation in both p53 and K-ras were extremely rare. There was no association between the mutations and expression pattern of K-ras, APC and p53 (p>0.05). In Indians, the frequency of alterations of K-ras and APC is similar as in Westerns, whereas the frequency of p53 mutation is slightly lower. The lack of multiple mutations in tumor specimens suggests that these genetic alterations might have independent influences on CRC development and there could be multiple alternative genetic pathways to CRC in our present study cohort. PMID:23526092

  9. 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.

  10. 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

  11. Colorectal Cancer Coalition

    MedlinePlus

    ... Million Strong Shop Join the Movement Share Your Story Check our Calendar Colorectal Support Community Latest News Help Wanted Read Blogs Get Social Free Printable Coloring Sheets Action Alerts About Our ...

  12. 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

  13. Nutrients, Foods, and Colorectal Cancer Prevention

    PubMed Central

    Song, Mingyang; Garrett, Wendy S.; Chan, Andrew T.

    2015-01-01

    Diet has an important role in the development of colorectal cancer. In the past few decades, findings from extensive epidemiologic and experimental investigation have linked consumption of several foods and nutrients to the risk of colorectal neoplasia. Calcium, fiber, milk, and whole grain have been associated with a lower risk of colorectal cancer, and red meat and processed meat with an increased risk. There is substantial evidence for the potential chemopreventive effects of vitamin D, folate, fruits and vegetables. Nutrients and foods may also interact, as a dietary pattern, to influence colorectal cancer risk. Diet likely influences colorectal carcinogenesis through several interacting mechanisms. These include the direct effects on immune responsiveness and inflammation, and the indirect effects of over-nutrition and obesity—risk factors for colorectal cancer. Emerging evidence also implicates the gut microbiota as an important effector in the relationship between diet and cancer. Dietary modification therefore has the promise of reducing colorectal cancer incidence. PMID:25575572

  14. Telomere function in colorectal cancer.

    PubMed

    Frías, Cristina; Morán, Alberto; de Juan, Carmen; Ortega, Paloma; Fernández-Marcelo, Tamara; Sánchez-Pernaute, Andrés; Torres, Antonio José; Díaz-Rubio, Eduardo; Benito, Manuel; Iniesta, Pilar

    2009-10-15

    Colorectal cancer is the third most common form of cancer and the second leading cause of cancer-related death in the western world. Tumour cells acquire the hallmarks of cancer during the carcinogenic selection process. Cell immortality is one of the principal features acquired during this process which involves the stabilization of telomere length. It is achieved mainly, by telomerase activation. Thus, the discovery of telomeres and telomerase allowed an understanding of the mechanisms by which cells can become immortalized. Different studies have shown that tumour cells have shorter telomeres than nontumour cells and have detected telomerase activity in the majority of tumours. Survival studies have determined that telomere maintenance and telomerase activity are associated with poor prognosis. Taking into account all the results achieved by different groups, quantification and evaluation of telomerase activity and measurement of telomere length may be useful methods for additional biologic and prognostic staging of colorectal carcinoma. PMID:21160767

  15. 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

  16. ADAMTS Expression in Colorectal Cancer

    PubMed Central

    Filou, Serafula; Korpetinou, Aggeliki; Kyriakopoulou, Dora; Bounias, Dimitrios; Stavropoulos, Michael; Ravazoula, Panagiota; Papachristou, Dionysios J.; Theocharis, Achilleas D.; Vynios, Demitrios H.

    2015-01-01

    ADAMTSs are a family of secreted proteinases that share the metalloproteinase domain with matrix metalloproteinases (MMPs). By acting on a large panel of extracellular substrates, they control several cell functions such as fusion, adhesion, proliferation and migration. Through their thrombospondin motifs they also possess anti-angiogenic properties. We investigated whether ADAMTSs participate in colorectal cancer progression and invasion. Their expression was investigated at both mRNA and protein levels. Using RT-PCR, the expression of ADAMTS-1, -4, -5 and ADAMTS-20 was estimated in colorectal tumors of different cancer stage and anatomic site and 3 cell lines of different aggressiveness. An overexpression of ADAMTS-4 and -5 was observed, especially in tissue samples, whereas ADAMTS-1 and -20 were found to be down-regulated. Western blot analysis further supported the RT-PCR findings, revealing in addition the degradation of ADAMTS-1 and -20 in cancer. In situ expression and localization of ADAMTS-1, -4, -5 and -20 was also investigated by immunohistochemical analysis. Our data suggest a positive correlation between ADAMTS-4 and -5 expression and cancer progression, in contrast with the anti-angiogenic members of the family, ADAMTS-1 and -20, which were found to be down-regulated. Our findings support the notion that overexpression of ADAMTS-4 and ADAMTS-5 in colorectal cancer might be a possible invasive mechanism of cancer cells in order to degrade proteoglycans of ECM. PMID:25786261

  17. Colorectal Cancer With Multiple Metachronous Metastasis Achieving Complete Remission 14 Years After Surgical Resection: Report of a Case

    PubMed Central

    Murono, Koji; Kawai, Kazushige; Kazama, Shinsuke; Tsuno, Nelson H.; Sunami, Eiji; Kitayama, Joji; Watanabe, Toshiaki

    2013-01-01

    A 63-year-old man underwent a colectomy for sigmoid colon cancer in 1997. The upper lobe of his left lung and his left adrenal gland were resected because of metachronous metastases, 7 and 10 years after the initial surgery, respectively. Recurrence of metastases to the middle lobe of the right lung and left adrenal gland were sequentially detected in 2007, and a multimodal therapy, consisting of the combination of radiotherapy and chemotherapy, was conducted since 2007. The chemotherapy included drugs such as FOLFOX, FOLFIRI, bevacizumab, capecitabine, and cetuximab. In 2011, the complete response of all metastatic lesions could be achieved, and no recurrence was detected for more than 1 year. In spite of repeated recurrences, by the combination of surgical resection, chemotherapy, and radiotherapy, the complete response could be achieved 14 years after the initial surgical resection, which can be attributed to the development of new treatment modalities and new agents for colorectal cancer. PMID:23438276

  18. 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 » ...

  19. 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 ...

  20. Loss of nuclear localization of TET2 in colorectal cancer.

    PubMed

    Huang, Yuji; Wang, Guanghui; Liang, Zhonglin; Yang, Yili; Cui, Long; Liu, Chen-Ying

    2016-01-01

    5-Hydroxymethylcytosine (5hmC) is lost in multiple human cancers, including colorectal cancer (CRC). Decreased ten-eleven translocation 1 (TET1) messenger RNA (mRNA), but not other two TET family members, has been observed in the colorectal cancer and is crucial for colorectal cancer initiation. Here, we show that nuclear localization of TET2 was lost in a significant portion of CRC tissues, in association with metastasis. In CRC cells, nuclear expression of TET2 were absent but not TET3. Nuclear export inhibitor can increase the 5hmC level in CRC cells, probably through regulating TET2. Our results indicate a new mechanism of TET2 dysregulation in colorectal cancer. PMID:26816554

  1. Potential Targets for Colorectal Cancer Prevention

    PubMed Central

    Temraz, Sally; Mukherji, Deborah; Shamseddine, Ali

    2013-01-01

    The step-wise development of colorectal neoplasia from adenoma to carcinoma suggests that specific interventions could delay or prevent the development of invasive cancer. Several key factors involved in colorectal cancer pathogenesis have already been identified including cyclooxygenase 2 (COX-2), nuclear factor kappa B (NF-κB), survivin and insulin-like growth factor-I (IGF-I). Clinical trials of COX-2 inhibitors have provided the “proof of principle” that inhibition of this enzyme can prevent the formation of colonic adenomas and potentially carcinomas, however concerns regarding the potential toxicity of these drugs have limited their use as a chemopreventative strategy. Curcumin, resveratrol and quercetin are chemopreventive agents that are able to suppress multiple signaling pathways involved in carcinogenesis and hence are attractive candidates for further research. PMID:23975167

  2. COGENT (COlorectal cancer GENeTics) revisited

    PubMed Central

    Houlston, Richard S.

    2012-01-01

    Many colorectal cancers (CRCs) develop in genetically susceptible individuals most of whom are not carriers of germ line mismatch repair or APC gene mutations and much of the heritable risk of CRC appears to be attributable to the co-inheritance of multiple low-risk variants. The accumulated experience to date in identifying this class of susceptibility allele has highlighted the need to conduct statistically and methodologically rigorous studies and the need for the multi-centre collaboration. This has been the motivation for establishing the COGENT (COlorectal cancer GENeTics) consortium which now includes over 20 research groups in Europe, Australia, the Americas, China and Japan actively working on CRC genetics. Here, we review the rationale for identifying low-penetrance variants for CRC and the current and future challenges for COGENT. PMID:22294761

  3. Ovarian metastasis from colorectal cancer.

    PubMed

    Birnkrant, A; Sampson, J; Sugarbaker, P H

    1986-11-01

    Controversies exist regarding the surgical treatment of the ovaries in women with primary colorectal cancer. A review of the authors' experience and the surgical literature reveals an incidence of ovarian metastases from colorectal cancer of approximately 6 percent. This problem may occur somewhat more frequently in premenopausal women. Resection of the ovaries at the time of colectomy is unlikely to affect survival. Removal of the ovaries at the time of bowel resection will prevent repeat laparotomy to resect an ovarian mass in approximately 2 percent of women with large bowel cancer. Oophorectomy should be performed in all postmenopausal females at the time of primary resection. Oophorectomy should be performed in premenopausal women if any gross abnormality of the ovary is detected or if peritoneal implants are seen at the time of primary resection. PMID:3533472

  4. Colorectal Cancer Screening, Version 1.2015.

    PubMed

    Provenzale, Dawn; Jasperson, Kory; Ahnen, Dennis J; Aslanian, Harry; Bray, Travis; Cannon, Jamie A; David, Donald S; Early, Dayna S; Erwin, Deborah; Ford, James M; Giardiello, Francis M; Gupta, Samir; Halverson, Amy L; Hamilton, Stanley R; Hampel, Heather; Ismail, Mohammad K; Klapman, Jason B; Larson, David W; Lazenby, Audrey J; Lynch, Patrick M; Mayer, Robert J; Ness, Reid M; Rao, M Sambasiva; Regenbogen, Scott E; Shike, Moshe; Steinbach, Gideon; Weinberg, David; Dwyer, Mary A; Freedman-Cass, Deborah A; Darlow, Susan

    2015-08-01

    The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colorectal Cancer Screening provide recommendations for selecting individuals for colorectal cancer screening, and for evaluation and follow-up of colon polyps. These NCCN Guidelines Insights summarize major discussion points of the 2015 NCCN Colorectal Cancer Screening panel meeting. Major discussion topics this year were the state of evidence for CT colonography and stool DNA testing, bowel preparation procedures for colonoscopy, and guidelines for patients with a positive family history of colorectal cancer. PMID:26285241

  5. Subnuclear Proteomics in Colorectal Cancer

    PubMed Central

    Albrethsen, Jakob; Knol, Jaco C.; Piersma, Sander R.; Pham, Thang V.; de Wit, Meike; Mongera, Sandra; Carvalho, Beatriz; Verheul, Henk M. W.; Fijneman, Remond J. A.; Meijer, Gerrit A.; Jimenez, Connie R.

    2010-01-01

    Abnormalities in nuclear phenotype and chromosome structure are key features of cancer cells. Investigation of the protein determinants of nuclear subfractions in cancer may yield molecular insights into aberrant chromosome function and chromatin organization and in addition may yield biomarkers for early cancer detection. Here we evaluate a proteomics work flow for profiling protein constituents in subnuclear domains in colorectal cancer tissues and apply this work flow to a comparative analysis of the nuclear matrix fraction in colorectal adenoma and carcinoma tissue samples. First, we established the reproducibility of the entire work flow. In a reproducibility analysis of three nuclear matrix fractions independently isolated from the same colon tumor homogenate, 889 of 1,047 proteins (85%) were reproducibly identified at high confidence (minimally two peptides per protein at 99% confidence interval at the protein level) with an average coefficient of variance for the number of normalized spectral counts per protein of 30%. This indicates a good reproducibility of the entire work flow from biochemical isolation to nano-LC-MS/MS analysis. Second, using spectral counting combined with statistics, we identified proteins that are significantly enriched in the nuclear matrix fraction relative to two earlier fractions (the chromatin-binding and intermediate filament fractions) isolated from six colorectal tissue samples. The total data set contained 2,059 non-redundant proteins. Gene ontology mining and protein network analysis of nuclear matrix-enriched proteins revealed enrichment for proteins implicated in “RNA processing” and “mRNA metabolic process.” Finally, an explorative comparison of the nuclear matrix proteome in colorectal adenoma and carcinoma tissues revealed many proteins previously implicated in oncogenesis as well as new candidates. A subset of these differentially expressed proteins also exhibited a corresponding change at the mRNA level

  6. [Maintenance therapy for colorectal cancer].

    PubMed

    Yamaguchi, Shigeo; Kato, Shunsuke

    2014-08-01

    Some trials have demonstrated the benefits of maintenance chemotherapy for advanced colorectal cancer. In chemotherapeutic strategies for advanced colorectal cancer, chemotherapy-related toxicity prevention and quality of life(QOL)maintenance are more important than the introduction of a strong regimen, especially when additional surgery is not possible. In Japan, the combination of a folinic acid/5-fluorouracil/oxaliplatin(FOLFOX)regimen and bevacizumab is a popular first-line chemotherapy regimen. However, despite its effectiveness, neuropathy or hand-foot syndrome after 5 or 6 cycles tends to lead to chemotherapy withdrawal. CAIRO3 trial reported the effectiveness of capecitabine and bevacizumab as a maintenance chemotherapy regimen. Additionally, the ML18147 trial demonstrated that bevacizumab beyond progression(BBP)prolonged overall survival(OS)and progression free survival(PFS)in patients with advanced colorectal cancer. Although those trials demonstrated the effectiveness of continuous or maintenance bevacizumab administration, no trials have compared the effectiveness of cytotoxic drugs with bevacizumab as maintenance therapies. Moreover, controversy exists regarding the selection of drugs as a maintenance therapy and the identification of patients who would benefit from maintenance therapy. PMID:25132024

  7. 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

  8. 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

  9. Red Meat and Colorectal Cancer.

    PubMed

    Aykan, Nuri Faruk

    2015-02-10

    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

  10. [A long-term survivor of colorectal cancer associated with multiple liver metastases and peritoneal carcinomatosis treated through a multidisciplinary approach].

    PubMed

    Tajima, Yusuke; Ishibashi, Keiichiro; Matsuzawa, Takeaki; Ishiguro, Toru; Ohsawa, Tomonori; Okada, Norimichi; Kumamoto, Kensuke; Kumagai, Youichi; Baba, Hiroyuki; Haga, Norihiro; Ishida, Hideyuki

    2012-11-01

    Even in the era of new anticancer drugs, an optimal treatment strategy for colorectal cancer associated with liver metastasis and peritoneal carcinomatosis has yet to be established. Here we report the case of a long-term survivor with very advanced colon cancer who underwent repeated resective surgery and chemotherapy. This 69-year-old man underwent a Hartmann's procedure and the resection of peritoneal metastases of cancer of the rectosigmoid, which had infiltrated the retroperitoneum giving rise to multiple liver metastases and peritoneal carcinomatosis. The resection margin was positive for cancer. After 14 courses of a modified FOLFOX6 (mFOLFOX6) regimen, a partial response with no development of new lesions was obtained. Multiple partial hepatectomies were subsequently performed. After the completion of an additional 6 courses of mFOLFOX6, a positron-emission tomography (PET)/computed tomography (CT) examination demonstrated a hot spot in segment 4. This hot deposit disappeared after a further 8 courses of mFOLFOX6. The patient then underwent a left lateral segmentectomy for a newly developed lesion in segment 3, which was detected 2 years and 7 months after the first operation. The patient has remained free from recurrence for 2 years since his last operation. PMID:23268036

  11. 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.

  12. Liver Metastases in Colorectal Cancer.

    PubMed

    Folprecht, Gunnar

    2016-01-01

    Resection of colorectal liver metastases is a treatment standard because patients experience long-term disease-free survival or are even cured after undergoing this procedure. Improved surgical techniques for liver resection in combination with downsizing liver metastases by chemotherapy, interventions to induce liver hypertrophy before resection, and the use of ablative techniques have allowed us to expand the indications for liver surgery and local treatment in situations with limited metastatic colorectal cancer. Resectability and identification of patients who might benefit from liver surgery and local ablative techniques are key factors for the treatment of patients with colorectal cancer. Despite the wide acceptance of liver surgery and ablative techniques, there are many open questions on the management of limited metastatic disease, such as which patients benefit from an aggressive surgical approach, what the indications for ablative and other local techniques are, and what the role of chemotherapy is for patients with resectable or resected disease. Unfortunately, results of randomized trials are only available for a limited number of these questions. PMID:27249722

  13. 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…

  14. Economic Burden of Colorectal Cancer in Korea

    PubMed Central

    Byun, Ju-Young; Oh, In-Hwan; Kim, Young Ae; Seo, Hye-Young; Lee, Yo-Han

    2014-01-01

    Objectives The incidence and survival rate of colorectal cancer in Korea are increasing because of improved screening, treatment technologies, and lifestyle changes. In this aging population, increases in economic cost result. This study was conducted to estimate the economic burden of colorectal cancer utilizing claims data from the Health Insurance Review and Assessment Service. Methods Economic burdens of colorectal cancer were estimated using prevalence data and patients were defined as those who received ambulatory treatment from medical institutions or who had been hospitalized due to colorectal cancer under the International Classification of Disease 10th revision codes from C18-C21. The economic burdens of colorectal cancer were calculated as direct costs and indirect costs. Results The prevalence rate (per 100 000 people) of those who were treated for colorectal cancer during 2010 was 165.48. The economic burdens of colorectal cancer in 2010 were 3 trillion and 100 billion Korean won (KRW), respectively. Direct costs included 1 trillion and 960 billion KRW (62.85%), respectively and indirect costs were 1 trillion and 160 billion (37.15%), respectively. Conclusions Colorectal cancer has a large economic burden. Efforts should be made to reduce the economic burden of the disease through primary and secondary prevention. PMID:24744825

  15. DNA Methylation and Colorectal Cancer

    PubMed Central

    Ashktorab, Hassan; Brim, Hassan

    2014-01-01

    Colorectal cancer (CRC) is one of the major cancers in the world and second death-causing cancer in the US. CRC development involves genetic and epigenetic alterations. Changes in DNA methylation status are believed to be involved at different stages of CRC. Promoter silencing via DNA methylation and hypomethylation of oncogenes alter genes’ expression, and can be used as a tool for the early detection of colonic lesions. DNA methylation use as diagnostic and prognostic marker has been described for many cancers including CRC. CpG Islands Methylator Phenotype (CIMP) is one of the underlying CRC mechanisms. This review aims to define methylation signatures in CRC. The analysis of DNA methylation profile in combination with the pathological diagnosis would be useful in predicting CRC tumors’ evolution and their prognostic behavior. PMID:25580099

  16. 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

  17. 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

  18. Translation initiation in colorectal cancer.

    PubMed

    Parsyan, Armen; Hernández, Greco; Meterissian, Sarkis

    2012-06-01

    Colorectal cancers (CRC) are one of the most common causes of morbidity and mortality in high-income countries. Targeted screening programs have resulted in early treatment and a substantial decrease in mortality. However, treatment strategies for CRC still require improvement. Understanding the etiology and pathogenesis of CRC would provide tools for improving treatment of patients with this disease. It is only recently that deregulation of the protein synthesis apparatus has begun to gain attention as a major player in cancer development and progression. Among the numerous steps of protein synthesis, deregulation of the process of translation initiation appears to play a key role in cancer growth and proliferation. This manuscript discusses a fascinating and rapidly growing field exploring translation initiation as a fundamental component in CRC development and progression and summarizing CRC treatment perspectives based on agents targeting translation initiation. PMID:22418835

  19. Biomarkers in Colorectal Cancer Screening.

    PubMed

    Nguyen, Minhhuyen T; Weinberg, David S

    2016-08-01

    Colorectal cancer (CRC) is the third most common cause of cancer death in men and women in the United States. The main goals of screening are to prevent carcinogenesis (via adenoma detection and removal) and detect cancer at an early, curable stage. CRC mortality is steadily dropping in the United States, partly because of greater screening utilization. However, nearly 1 in 3 average-risk people are not up to date with standard CRC screening recommendations. This review surveys a wide range of CRC biomarkers in various stages of development, which may offer attractive risk stratification tools; a few have reached the commercial stage. If widely accepted, these tools may contribute to shift CRC screening practices away from 1-step colonoscopy to a 2-step risk stratification process of predictive biomarker measurements followed by colonoscopy for lower-risk patients with a positive result. Such strategies could potentially increase the rate of CRC screening. PMID:27496118

  20. Biomarkers of Angiogenesis in Colorectal Cancer

    PubMed Central

    Mousa, Luay; Salem, Mohamed E.; Mikhail, Sameh

    2015-01-01

    Colorectal cancer (CRC) is the third most common cancer worldwide and accounts for 10% of all new cancer diagnoses. Angiogenesis is a tightly regulated process that is mediated by a group of angiogenic factors such as vascular endothelial growth factor and its receptors. Given the widespread use of antiangiogenic agents in CRC, there has been considerable interest in the development of methods to identify novel markers that can predict outcome in the treatment of this disease with angiogenesis inhibitors. Multiple biomarkers are in various phases of development and include tissue, serum, and imaging biomarkers. The complexity of the angiogenesis pathway and the overlap between the various angiogenic factors present a significant challenge to biomarker discovery. In our review, we discuss the angiogenesis pathway and the most promising evolving concepts in biomarker discovery, as well as highlight the landmark studies that identify subgroups of patients with CRC who may preferentially benefit from angiogenesis inhibitors. PMID:26543385

  1. Smoking and risk of colorectal cancer.

    PubMed Central

    Knekt, P.; Hakama, M.; Järvinen, R.; Pukkala, E.; Heliövaara, M.

    1998-01-01

    Tobacco smoking was studied in relation to colorectal cancer in 56 973 Finnish men and women initially free from cancer. Smoking status was determined by a health questionnaire. During a follow-up period of 28 years, from the baseline in 1966-72 to the end of 1994, 457 cases of colorectal cancer occurred. There was no significant association between baseline smoking status and colorectal cancer risk over the total follow-up period. The sex- and age-adjusted relative risk of colorectal cancer between smokers and non-smokers was 1.06 (95% confidence interval 0.84-1.33). For follow-up periods of 11-20 years, however, the relative risk was 1.57 (95% confidence interval 1.09-2.24). In a subgroup in which smoking habits were assessed twice, the relative risk of colorectal cancer among persistent smokers was 1.71 (95% confidence interval 1.09-2.68) compared with others. The results of the present prospective study are consistent with the possibility that smoking increases the risk of colorectal cancer after a relatively long induction period. To clarify the role of smoking in colorectal cancer development, further cohort studies are needed with long follow-up periods and allowing for control of dietary and other potential confounding factors. PMID:9662264

  2. 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

  3. Participation and barriers to colorectal cancer screening in Malaysia.

    PubMed

    Yusoff, Harmy Mohamed; Daud, Norwati; Noor, Norhayati Mohd; Rahim, Amry Abdul

    2012-01-01

    In Malaysia, colorectal cancer is the most common cancer in males and the third most common in females. Mortality due to colorectal cancer can be effectively reduced with early diagnosis. This study was designed to look into colorectal cancer screening participation and its barriers among average risk individuals in Malaysia. A cross sectional study was conducted from August 2009 till April 2010 involving average risk individuals from 44 primary care clinics in West Malaysia. Each individual was asked whether they have performed any of the colorectal cancer screening methods in the past five years. The barrier questions had three domains: patient factors, test factors and health care provider factors. Descriptive analysis was achieved using Statistical Program for Social Sciences (SPSS) version 12.0. A total of 1,905 average risk individuals responded making a response rate of 93.8%. Only 13 (0.7%) respondents had undergone any of the colorectal cancer screening methods in the past five years. The main patient and test factors for not participating were embarrassment (35.2%) and feeling uncomfortable (30.0%), respectively. There were 11.2% of respondents who never received any advice to do screening. The main reason for them to undergo screening was being advised by health care providers (84.6%). The study showed that participation in colorectal cancer screening in Malaysia is extremely low and multiple factors contribute to this situation. Given the importance of the disease, efforts should be made to increase colorectal cancer screening activities in Malaysia. PMID:23098504

  4. Hypoalbuminemia in colorectal cancer prognosis: Nutritional marker or inflammatory surrogate?

    PubMed Central

    Nazha, Bassel; Moussaly, Elias; Zaarour, Mazen; Weerasinghe, Chanudi; Azab, Basem

    2015-01-01

    Albumin is the single most abundant protein in the human serum. Its roles in physiology and pathology are diverse. Serum albumin levels have been classically thought to reflect the nutritional status of patients. This concept has been challenged in the last two decades as multiple factors, such as inflammation, appeared to affect albumin levels independent of nutrition. In general, cancer patients have a high prevalence of hypoalbuminemia. As such, the role of hypoalbuminemia in patients with colorectal cancer has received significant interest. We reviewed the English literature on the prognostic value of pretreatment albumin levels in colorectal cancer. We also consolidated the evidence that led to the current understanding of hypoalbuminemia as an inflammatory marker rather than as a nutritional one among patients with colorectal cancer. PMID:26730282

  5. 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

  6. Colorectal (Colon) Cancer: Questions to Ask Your Doctor

    MedlinePlus

    ... Stay Informed Cancer Home Questions to Ask Your Doctor About Colorectal Cancer Language: English Español (Spanish) Recommend ... helps pay for colorectal cancer screening. Ask Your Doctor Do I need to get a screening test ...

  7. 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

  8. 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

  9. 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

  10. 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 ...

  11. 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.

  12. Multiple epithelial and nonepithelial tumors in hereditary nonpolyposis colorectal cancer: characterization of germline and somatic mutations of the MSH2 gene and heterogeneity of replication error phenotypes.

    PubMed

    Huang, Rui-Len; Chao, Chung-Faye; Ding, Dah-Ching; Yu, Cheng-Ping; Chang, Cheng-Chang; Lai, Hung-Chen; Yu, Mu-Hsien; Liu, Hang-Seng; Chu, Tang-Yuan

    2004-09-01

    Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal inherited cancer syndrome characterized by germline plus somatic mutations of DNA mismatch repair genes and familial clustering of cancers of colorectum and other visceral organs. So far, to our knowledge, there has been no proof of nonepithelial tumors in association with HNPCC. Here we report on a MSH2 frameshift HNPCC family with a carrier found to have multiple primary tumors, including endometrial hyperplasia, ovarian adenocarcinoma, skin cavernous hemangioma, and skin dermatofibrosarcoma protuberans (DFSP). We studied the replication error (RER) phenotype in noncoding (Bat-26, Bat-25, D2S123, D5S346, and D17S250) and coding (MSH3, MSH6, BAX, and TGFBR2 genes) DNA sequences, and characterized the germline and somatic mutations of the MSH2 gene in the tumors described above and in endometrial carcinomas from two of her affected siblings. RER was observed in an order of hyperplasic endometrium (6/10 markers), ovarian carcinoma (5/10 markers), endometrial carcinomas (4/9 and 3/10), DFSP (2/9 markers), and cavernous hemangioma (2/10 markers). All the tumors showed the same germline mutation of G5-->G6 frameshift at 183-187 and polymorphism of C1168T in a heterozygous pattern. In an endometrial carcinoma, deletion of the second allele of MSH2 was evident. Heterogeneous RER patterns were noted in multiple primary tumors of the same individual and in premalignant and malignant endometrial tumors from different individuals. The study demonstrated the two hits of the hMSH(2) gene as well as intra- and interindividual variations of RER phenotypes in HNPCC. The first characterized nonepithelial tumors in HNPCC seem to carry a limited panel of RER, including a framesift at the (A)(10) tract of TGFBR2. PMID:15350299

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. Korean Guidelines for Colorectal Cancer Screening and Polyp Detection

    PubMed Central

    Lee, Bo-In; Hong, Sung Pil; Kim, Seong-Eun; Kim, Se Hyung; Hong, Sung Noh; Yang, Dong-Hoon; Shin, Sung Jae; Lee, Suck-Ho; Park, Dong Il; Kim, Young-Ho; Kim, Hyun Jung; Yang, Suk-Kyun; Kim, Hyo Jong; Jeon, Hae Jeong

    2012-01-01

    Now colorectal cancer is the second most common cancer in males and the fourth most common cancer in females in Korea. Since most of colorectal cancers occur after the prolonged transformation of adenomas into carcinomas, early detection and removal of colorectal adenomas are one of the most effective methods to prevent colorectal cancer. Considering the increasing incidence of colorectal cancer and polyps in Korea, it is very important to establish Korean guideline for colorectal cancer screening and polyp detection. The guideline was developed by the Korean Multi-Society Take Force and we tried to establish the guideline by evidence-based methods. Parts of the statements were draw by systematic reviews and meta-analyses. Herein we discussed epidemiology of colorectal cancers and adenomas in Korea and optimal methods for screening of colorectal cancer and detection of adenomas including fecal occult blood tests, radiologic tests, and endoscopic examinations. PMID:22741131

  18. [Treatment outcome of peptide vaccination for advanced colorectal cancer].

    PubMed

    Sugiura, Fumiaki; Inoue, Keisuke; Kogita, Akihiro; Yoshioka, Yasumasa; Hida, Jinichi; Okuno, Kiyotaka; Sukegawa, Yasushi

    2013-11-01

    Complementary DNA( cDNA) microarray technology coupled with laser microdissection has been used to identify human leukocyte antigen (HLA)-A24-restricted epitope peptides as potential targets for cancer vaccination in colorectal cancer patients. These antigenic peptides were derived from 2 different cancer-testis antigens, ring finger protein 43 (RNF43) and translocase of outer mitochondrial membrane 34( TOMM34). We conducted a clinical trial of colorectal cancer-specific peptide( RNF43, TOMM34) vaccines with uracil/tegafur( UFT)+Leucovorin( LV) for the treatment of advanced or recurrent colorectal cancer. The vaccinations were well tolerated without any serious adverse events. There were long-term survivors in the group showing cytotoxic T lymphocyte (CTL) responses against both RNF43 and TOMM34, as well as in the group showing CTL responses against either RNF43 or TOMM34. A new study has been planned to obtain more immunological responses. We started a clinical trial of vaccines against multiple peptides (RNF43, TOMM34, forkhead box protein M1 [FOXM1], maternal embryonic leucine zipper kinase [MELK], holliday junction recognition protein[HJURP], vascular endothelial growth factor receptor 1[VEGFR1], and VEGFR2) for the treatment of advanced or recurrent colorectal cancer. PMID:24393856

  19. What Should You Ask Your Doctor about Colorectal Cancer?

    MedlinePlus

    ... colorectal cancer survivor What should you ask your doctor about colorectal cancer? It’s important to have frank, ... treatment? Do I need to see any other doctors or health professionals? If I’m concerned about ...

  20. 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.

  1. Colorectal Cancer Screening in Vietnamese Americans

    PubMed Central

    Nguyen, Bang H.

    2008-01-01

    Background Rates of colorectal cancer screening in Vietnamese Americans are lower than those in non-Hispanic whites. This paper describes rates of colorectal screening, identifies determinants, and recommends educational strategies to improve screening. Methods A cross-sectional sample of 867 Vietnamese aged 50 to 74 drawn from a sampling frame of individuals in the Alameda and Santa Clara Counties, California and Harris County, Texas area telephone directories with Vietnamese surnames were interviewed in 2004. Results Colorectal screening recognition, receipt, currency, and intention rates were low. Conclusions: While the screening rates are low, Vietnamese are receptive to screening if providers recommend it. PMID:18444045

  2. New era of colorectal cancer screening

    PubMed Central

    El Zoghbi, Maysaa; Cummings, Linda C

    2016-01-01

    Colorectal cancer (CRC) is the 2nd most common cancer in women and 3rd most common cancer in men worldwide. Most CRCs develop from adenomatous polyps arising from glandular epithelium. Tumor growth is initiated by mutation of the tumor suppressor gene APC and involves other genetic mutations in a stepwise process over years. Both hereditary and environmental factors contribute to the development of CRC. Screening has been proven to reduce the incidence of CRC. Screening has also contributed to the decrease in CRC mortality in the United States. However, CRC incidence and/or mortality remain on the rise in some parts of the world (Eastern Europe, Asia, and South America), likely due to factors including westernized diet, lifestyle, and lack of healthcare infrastructure. Multiple screening options are available, ranging from direct radiologic or endoscopic visualization tests that primarily detect premalignant or malignant lesions such as flexible sigmoidoscopy, optical colonoscopy, colon capsule endoscopy, computed tomographic colonography, and double contrast barium enema - to stool based tests which primarily detect cancers, including fecal DNA, fecal immunochemical test, and fecal occult blood test. The availability of some of these tests is limited to areas with high economic resources. This article will discuss CRC epidemiology, pathogenesis, risk factors, and screening modalities with a particular focus on new technologies. PMID:26981176

  3. Increased MUTYH mutation frequency among Dutch families with breast cancer and colorectal cancer.

    PubMed

    Wasielewski, Marijke; Out, Astrid A; Vermeulen, Joyce; Nielsen, Maartje; van den Ouweland, Ans; Tops, Carli M J; Wijnen, Juul T; Vasen, Hans F A; Weiss, Marjan M; Klijn, Jan G M; Devilee, Peter; Hes, Frederik J; Schutte, Mieke

    2010-12-01

    Homozygous and compound heterozygous MUTYH mutations predispose for MUTYH-associated polyposis (MAP). The clinical phenotype of MAP is characterised by the multiple colorectal adenomas and colorectal carcinoma. We previously found that female MAP patients may also have an increased risk for breast cancer. Yet, the involvement of MUTYH mutations in families with both breast cancer and colorectal cancer is unclear. Here, we have genotyped the MUTYH p.Tyr179Cys, p.Gly396Asp and p.Pro405Leu founder mutations in 153 Dutch families with breast cancer patients and colorectal cancer patients. Families were classified as polyposis, revised Amsterdam criteria positive (FCRC-AMS positive), revised Amsterdam criteria negative (FCRC-AMS negative), hereditary breast and colorectal cancer (HBCC) and non-HBCC breast cancer families. As anticipated, biallelic MUTYH mutations were identified among 13% of 15 polyposis families, which was significantly increased compared to the absence of biallelic MUTYH mutations in the population (P = 0.0001). Importantly, six heterozygous MUTYH mutations were identified among non-polyposis families with breast and colorectal cancer. These mutations were identified specifically in FCRC-AMS negative and in HBCC breast cancer families (11% of 28 families and 4% of 74 families, respectively; P = 0.02 for both groups combined vs. controls). Importantly, the 11% MUTYH frequency among FCRC-AMS negative families was almost fivefold higher than the reported frequencies for FCRC-AMS negative families unselected for the presence of breast cancer patients (P = 0.03). Together, our results indicate that heterozygous MUTYH mutations are associated with families that include both breast cancer patients and colorectal cancer patients, independent of which tumour type is more prevalent in the family. PMID:20191381

  4. 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

  5. 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

  6. 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 ...

  7. 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. PMID:26559156

  8. 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

  9. Mini-invasive surgery for colorectal cancer

    PubMed Central

    Zeng, Wei-Gen; Zhou, Zhi-Xiang

    2014-01-01

    Laparoscopic techniques have been extensively used for the surgical management of colorectal cancer during the last two decades. Accumulating data have demonstrated that laparoscopic colectomy is associated with better short-term outcomes and equivalent oncologic outcomes when compared with open surgery. However, some controversies regarding the oncologic quality of mini-invasive surgery for rectal cancer exist. Meanwhile, some progresses in colorectal surgery, such as robotic technology, single-incision laparoscopic surgery, natural orifice specimen extraction, and natural orifice transluminal endoscopic surgery, have been made in recent years. In this article, we review the published data and mainly focus on the current status and latest advances of mini-invasive surgery for colorectal cancer. PMID:24589210

  10. 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

  11. 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

  12. 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

  13. 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 ...

  14. Survival of patients with hereditary colorectal cancer: comparison of HNPCC and colorectal cancer in FAP patients with sporadic colorectal cancer.

    PubMed

    Bertario, L; Russo, A; Sala, P; Eboli, M; Radice, P; Presciuttini, S; Andreola, S; Rodriguez-Bigas, M A; Pizzetti, P; Spinelli, P

    1999-01-18

    Conflicting data exist on the prognosis of hereditary colorectal cancer. HNPCC patients, in particular, are often reported to have a better survival. We examined 2,340 colorectal-cancer patients treated in our Institution: 144 HNPCC patients (Amsterdam Criteria), 161 FAP patients and 2,035 patients with sporadic cancer. Data on hereditary-cancer patients treated between 1980 and 1995 was collected in a registry. The 2,035 sporadic colorectal-cancer patients (controls) included all new cases treated in the Department of Gastrointestinal-Tract Surgery during the same period. Observed survival was estimated using the Kaplan-Meier method. Cumulative survival probability was estimated at 5 years within each group and stratified by various clinical and pathological variables. The age distribution at diagnosis of sporadic patients was significantly higher than that of FAP and HNPCC patients (median 60 years vs. 43 and 49 years; p < 0.0001). In the HNPCC group, 40% had a right cancer location, vs. 14% in the FAP group and 13% in the sporadic-cancer group. In the sporadic group, 51% were early-stage cancers (Dukes A or B) vs. 48.4% and 52.1% in the FAP and HNPCC groups respectively. In the HNPCC, FAP and sporadic-cancer groups, the 5-year cumulative survival rate was 56.9%, 54.4% and 50.6% respectively. Survival analysis by the Cox proportional-hazards method revealed no substantial survival advantage for HNPCC and FAP patients compared with the sporadic group, after adjustment for age, gender, stage and tumor location. The hazard ratio for HNPCC was 1.01 (95% CI 0.72-1.39) and 1.27 (95% CI 0.95-1.7) for FAP patients compared with the sporadic-colorectal-cancer group. PMID:9935197

  15. Promoting Colorectal Cancer Screening Discussion

    PubMed Central

    Christy, Shannon M.; Perkins, Susan M.; Tong, Yan; Krier, Connie; Champion, Victoria L.; Skinner, Celette Sugg; Springston, Jeffrey K.; Imperiale, Thomas F.; Rawl, Susan M.

    2013-01-01

    Background Provider recommendation is a predictor of colorectal cancer (CRC) screening. Purpose To compare the effects of two clinic-based interventions on patient–provider discussions about CRC screening. Design Two-group RCT with data collected at baseline and 1 week post-intervention. Participants/setting African-American patients that were non-adherent to CRC screening recommendations (n=693) with a primary care visit between 2008 and 2010 in one of 11 urban primary care clinics. Intervention Participants received either a computer-delivered tailored CRC screening intervention or a nontailored informational brochure about CRC screening immediately prior to their primary care visit. Main outcome measures Between-group differences in odds of having had a CRC screening discussion about a colon test, with and without adjusting for demographic, clinic, health literacy, health belief, and social support variables, were examined as predictors of a CRC screening discussion using logistic regression. Intervention effects on CRC screening test order by PCPs were examined using logistic regression. Analyses were conducted in 2011 and 2012. Results Compared to the brochure group, a greater proportions of those in the computer-delivered tailored intervention group reported having had a discussion with their provider about CRC screening (63% vs 48%, OR=1.81, p<0.001). Predictors of a discussion about CRC screening included computer group participation, younger age, reason for visit, being unmarried, colonoscopy self-efficacy, and family member/friend recommendation (all p-values <0.05). Conclusions The computer-delivered tailored intervention was more effective than a nontailored brochure at stimulating patient–provider discussions about CRC screening. Those who received the computer-delivered intervention also were more likely to have a CRC screening test (fecal occult blood test or colonoscopy) ordered by their PCP. Trial registration This study is registered at www

  16. 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

  17. 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

  18. Treatment of peritoneal metastases from colorectal cancer

    PubMed Central

    März, Loreen; Piso, Pompiliu

    2015-01-01

    Peritoneal seedings of a colorectal tumor represent the second most frequent site of metastasis (after the liver). In the era of 5-fluorouracil (5-FU)-only chemotherapy, the prognosis was poor for colorectal cancer with peritoneal metastases. Within the last few years, new chemotherapeutic and targeted agents have improved the prognosis; however, the response to these treatments seems to be lower than that for liver metastases. The combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy have further improved both disease-free survival and overall survival. Keeping this in mind, every patient presenting with peritoneal metastases from colorectal cancer should be evaluated and receive adequate treatment, if possible in the above-mentioned combination. This paper reviews recent advancements in the therapy of peritoneal carcinomatosis. PMID:26424828

  19. Emerging role of vitamin D in colorectal cancer.

    PubMed

    Kang, Wonmo; Lee, Sujin; Jeon, Eunyi; Yun, Ye-Rang; Kim, Kook-Hyun; Jang, Jun-Hyeog

    2011-08-15

    Colorectal cancer is a common cancer and the fourth leading cause of death in Korea. The incidence and mortality of colorectal cancer varies according to risk factors, such as age, family history, genetic history, food habits, and physical activities. Some studies have focused on the association between vitamin D and colorectal cancer. Today, there is growing evidence that high vitamin D intake and a plasma level of 25(OH)D(3) reduce the incidence of colorectal cancer by modifying cancer angiogenesis, cell apoptosis, differentiation, and proliferation. Taken together, these results suggest that vitamin D supplementation alone, or in combination with anti-cancer agents, might reduce the incidence of colorectal cancer. In this review, we discuss the function and mechanism of vitamin D including the effect of vitamin D on colorectal cancer. PMID:22007275

  20. Emerging role of vitamin D in colorectal cancer

    PubMed Central

    Kang, Wonmo; Lee, Sujin; Jeon, Eunyi; Yun, Ye-Rang; Kim, Kook-Hyun; Jang, Jun-Hyeog

    2011-01-01

    Colorectal cancer is a common cancer and the fourth leading cause of death in Korea. The incidence and mortality of colorectal cancer varies according to risk factors, such as age, family history, genetic history, food habits, and physical activities. Some studies have focused on the association between vitamin D and colorectal cancer. Today, there is growing evidence that high vitamin D intake and a plasma level of 25(OH)D3 reduce the incidence of colorectal cancer by modifying cancer angiogenesis, cell apoptosis, differentiation, and proliferation. Taken together, these results suggest that vitamin D supplementation alone, or in combination with anti-cancer agents, might reduce the incidence of colorectal cancer. In this review, we discuss the function and mechanism of vitamin D including the effect of vitamin D on colorectal cancer. PMID:22007275

  1. Iron homeostasis and distal colorectal adenoma risk in the prostate, lung, colorectal, and ovarian cancer screening trial.

    PubMed

    Cross, Amanda J; Sinha, Rashmi; Wood, Richard J; Xue, Xiaonan; Huang, Wen-Yi; Yeager, Meredith; Hayes, Richard B; Gunter, Marc J

    2011-09-01

    Red meat consumption has been positively associated with colorectal cancer; however, the biological mechanism underlying this relationship is not understood. Red meat is a major source of iron, which may play a role in colorectal carcinogenesis via increased crypt cell proliferation, cytotoxicity, and endogenous N-nitrosation. In a nested case-control study within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, we prospectively evaluated multiple iron exposure parameters, including dietary intake and serum measures of iron, ferritin, transferrin, total iron binding capacity (TIBC), and unsaturated iron binding capacity (UIBC) in relation to incident colorectal adenoma in 356 cases and 396 matched polyp-free controls. We also investigated variation in eight key genes involved in iron homeostasis in relation to colorectal adenoma in an additional series totaling 1,126 cases and 1,173 matched controls. We observed a positive association between red meat intake and colorectal adenoma [OR comparing extreme quartiles (OR(q4-q1)) = 1.59, 95% CI = 1.02-2.49, P(trend) = 0.03]. Serum TIBC and UIBC were inversely associated with colorectal adenoma (OR(q4-q1) = 0.57, 95% CI = 0.37-0.88, P(trend) = 0.03; and OR(q4-q1) = 0.62, 95% CI = 0.40-0.95, P(trend) = 0.04, respectively). Colorectal adenoma was not associated with serum ferritin, iron, or transferrin saturation or with polymorphisms in genes involved in iron homeostasis. Serum TIBC and UIBC, parameters that have a reciprocal relationship with overall iron load, were inversely related to colorectal adenoma, suggesting that individuals with lower iron status have a reduced risk of developing colorectal adenoma. PMID:21685236

  2. Metastatic Colorectal Cancer: Lessons Learned, Future Possibilities.

    PubMed

    Venook, Alan P

    2016-05-01

    Survival of patients with metastatic colorectal cancer has dramatically improved over the past 20 years, primarily because physicians have become adept at using the many regimens approved for this patient population. Future advances may come from understanding molecular subtypes, finding and treating new actionable mutations, and harnessing the immune system. PMID:27226509

  3. BK polyomavirus association with colorectal cancer development.

    PubMed

    Khabaz, M N; Nedjadi, T; Gari, M A; Al-Maghrabi, J A; Atta, H M; Basuni, A A; Elderwi, D A

    2016-01-01

    The development of human neoplasms can be provoked by exposure to one of several viruses. Burkitt lymphoma, cervical carcinoma, and hepatocellular carcinoma are associated with Epstein-Barr, human papilloma, and hepatitis B virus infections, respectively. Over the past three decades, many studies have attempted to establish an association between colorectal cancer and viruses, with debatable results. The aim of the present research was to assess the presence of BK polyomavirus (BKV) DNA and protein in colorectal cancer samples from patients in the Western Province of Saudi Arabia. DNA extracted from archival samples of colorectal cancer tissues was analyzed for BKV sequences using polymerase chain reaction (PCR)-based techniques. In addition, expression of a BKV protein was assessed using immunohistochemical staining. None of the tumor and control samples examined tested positive for BKV DNA in PCR assays. Furthermore, immunohistochemical staining failed to detect viral proteins in both cancer and control specimens. These results may indicate that BKV is not associated with the development of colorectal adenocarcinoma in patients in the Western Province of Saudi Arabia. PMID:27173319

  4. Nutrients Impact the Pathogenesis and Development of Colorectal Cancer

    PubMed Central

    Du, Wan; Fang, Jing-Yuan

    2016-01-01

    Background Colorectal cancer is a commonly diagnosed cancer and the cause of many cancer deaths worldwide. Nutrients might be crucial in the pathogenesis and development of colorectal cancer. Although a number of studies have demonstrated the potential effects of nutrients, many challenges still remain Summary A tremendous amount of research has emerged concerning the roles of nutrients in colorectal cancer during the past decades. Here, we review the latest research progress on nutrients, including vitamins, folic acid, calcium, selenium and dietary fiber, involved in colorectal cancer prevention Key Message Nutrients are commonly consumed in foods or dietary supplements. It is clear that nutrients could play an important role and influence colorectal cancer outcomes. The relationship between nutrients and colorectal risk is complex. Vitamins, folic acid, calcium, selenium and dietary fiber have been proposed as potential agents to prevent colorectal cancer. However, some studies found that these nutrients did not reduce the incidence of colorectal cancer Practical Implications The supplementary dose of nutrients, the length of time required to observe the effects and confounding factors during the study might influence the role of nutrients in the prevention of colorectal cancer. Therefore, more evidence from ongoing clinical trials with different population groups and longer follow-up periods is critical to determine the relationship between nutrients and colorectal cancer. PMID:27403415

  5. 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

  6. 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

  7. Vitamin B6 and colorectal cancer: Current evidence and future directions

    PubMed Central

    Zhang, Xue-Hong; Ma, Jing; Smith-Warner, Stephanie A; Lee, Jung Eun; Giovannucci, Edward

    2013-01-01

    Colorectal cancer remains the third most common cancer in both women and men worldwide. Identifying modifiable dietary factors is crucial in developing primary prevention strategies. Vitamin B6 is involved in more than 100 coenzyme reactions, and may influence colorectal cancer risk in multiple ways including through its role in one-carbon metabolism related DNA synthesis and methylation and by reducing inflammation, cell proliferation, and oxidative stress. Observational studies of dietary or dietary plus supplementary intake of vitamin B6 and colorectal cancer risk have been inconsistent with most studies reporting nonsignificant positive or inverse associations. However, published studies of plasma pyridoxal 5’-phosphate (the active form of vitamin B6) levels consistently support an approximately 30%-50% reduction in risk of colorectal cancer comparing high with low concentrations. The reasons for the discrepancy in the results between dietary-based and plasma-based studies remain unresolved. Other unresolved questions include the effects of vitamin B6 intake in early life (i.e., childhood or adolescence) and of suboptimal vitamin B6 status on colorectal cancer risk, whether the associations with vitamin B6 differ across molecular subtypes of colorectal cancer, and whether the vitamin B6-colorectal cancer association is modified by genetic variants of one-carbon metabolism. PMID:23467420

  8. 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.…

  9. Spatial Analysis of Colorectal Cancer in Iran.

    PubMed

    Pakzad, Reza; Moudi, Asieh; Pournamdar, Zahra; Pakzad, Iraj; Mohammadian-Hashejani, Abdollah; Momenimovahed, Zohre; Salehiniya, Hamid; Towhidi, Farhad; Makhsosi, Behnam Reza

    2016-01-01

    Colorectal cancer is one of the most common cancers. Due to demographic changes, it is predicted that the incidence of this cancer will increase. Variations of its incidence rate among geographical areas are due to various contributing factors. Since there have been a lack of studies on this topic in our country, the present assessment of spatial patterns of colorectal cancer incidence in Iran was performed. In this ecological study, the new cases of colon cancer were extracted from Cancer Registry Center report of the Health Deputy of Iran in 2009. The reported incidences of the disease were standardized on the basis of the World Health Organization population and the direct method. Then the data were inserted into the GIS software, and finally, using the analysis of hot spots (Getis-Ord Gi) high-risk areas were drawn. Provinces that are higher or lower than the national average (1.9 SD) were considered hot spots or cold spots, significant at the level of 0.05. A total of 6,210 cases of colorectal cancer were registered in Iran in 2009, of which 3,727 were in men and 2,783 in women (age-standardized rates of 11.3 and 10.9 per 100,000 population, respectively). The results showed that in central and northern Iran including Isfahan, Qom, Tehran, Qazvin and Mazandaran significant hot spots in men were present (p <0.05). In women also we have high incidence in northern and central states: Mazandaran province (p<0.01) and the province of Tehran (p<0.05) had higher incidences than the national average and were apparent as significant hot spots. Analysis of the spatial distribution of colorectal cancer showed significant differences between different areas pointing to the necessity for further epidemiological studies into the etiology and early detection. PMID:27165208

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. Colorectal cancer prognosis: is it all mutation, mutation, mutation?

    PubMed Central

    Hassan, A B; Paraskeva, C

    2005-01-01

    For the 500 000 new cases of colorectal cancer in the world each year, identification of patients with a worse prognosis and those who are more likely to respond to treatment is a challenge. There is an increasing body of evidence correlating genetic mutations with outcome in tumours derived from human colorectal cancer cohorts. K-ras, but not p53 or APC, mutations appear to be associated with poorer overall survival in colorectal cancer patients. PMID:16099785

  17. Telenovela: an innovative colorectal cancer screening health messaging tool

    PubMed Central

    Cueva, Melany; Kuhnley, Regina; Slatton, Jozieta; Dignan, Mark; Underwood, Emily; Landis, Kate

    2013-01-01

    Background Alaska Native people have nearly twice the rate of colorectal cancer (CRC) incidence and mortality as the US White population. Objective Building upon storytelling as a culturally respectful way to share information among Alaska Native people, a 25-minute telenovela-style movie, What's the Big Deal?, was developed to increase CRC screening awareness and knowledge, role-model CRC conversations, and support wellness choices. Design Alaska Native cultural values of family, community, storytelling, and humor were woven into seven, 3–4 minute movie vignettes. Written post-movie viewing evaluations completed by 71.3% of viewers (305/428) were collected at several venues, including the premiere of the movie in the urban city of Anchorage at a local movie theater, seven rural Alaska community movie nights, and five cancer education trainings with Community Health Workers. Paper and pencil evaluations included check box and open-ended questions to learn participants' response to a telenovela-style movie. Results On written-post movie viewing evaluations, viewers reported an increase in CRC knowledge and comfort with talking about recommended CRC screening exams. Notably, 81.6% of respondents (249/305) wrote positive intent to change behavior. Multiple responses included: 65% talking with family and friends about colon screening (162), 24% talking with their provider about colon screening (59), 31% having a colon screening (76), and 44% increasing physical activity (110). Conclusions Written evaluations revealed the telenovela genre to be an innovative way to communicate colorectal cancer health messages with Alaska Native, American Indian, and Caucasian people both in an urban and rural setting to empower conversations and action related to colorectal cancer screening. Telenovela is a promising health communication tool to shift community norms by generating enthusiasm and conversations about the importance of having recommended colorectal cancer screening

  18. 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

  19. microRNAs and Colorectal Cancer.

    PubMed

    Ress, Anna Lena; Perakis, Samantha; Pichler, Martin

    2015-01-01

    Colorectal cancer (CRC) is one of the most common types of human cancer with high cancer-related morbidity and mortality rates. The development and clinical validation of novel therapeutic avenues have improved the clinical outcome, but metastatic CRC still remains an incurable disease in most cases. The interest in discovering novel pathophysiological drivers in CRC is intensively ongoing and the search for novel biomarkers for early diagnosis, for patient's stratification for prognostic purposes or for predicting treatment response are warranted. microRNAs are small RNA molecules that regulate the expression of larger messenger RNA species by different mechanisms with the final consequence to provide a fine tuning tool for global gene expression patterns. First discovered in worms, around 15 years ago it became clear that microRNAs are also existing in humans and that they are widely involved in human carcinogenesis. Within the last years, tremendous progress in the understanding of microRNAs and their role in CRC carcinogenesis has been developed. In this book chapter, several examples of previously identified microRNAs and how they influence colorectal carcinogenesis will be discussed. The information starting at the underlying molecular mechanisms towards clinical applications will be depicted and an overview what great potential these small molecules might carry in future colorectal cancer medicine, will be discussed. PMID:26658998

  20. 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

  1. 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

  2. Ziv-aflibercept in metastatic colorectal cancer

    PubMed Central

    Patel, Anuj; Sun, Weijing

    2014-01-01

    The combination of cytotoxic chemotherapy and antiangiogenic agents has become a conventional treatment option for patients with metastatic colorectal cancer. Ziv-aflibercept is a fusion protein which acts as a decoy receptor for vascular endothelial growth factor (VEGF)-A, VEGF-B, and placental growth factor (PlGF); it was approved in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) for the treatment of patients with metastatic colorectal cancer that is resistant to or has progressed after an oxaliplatin-containing fluoropyrimidine-based regimen. Herein we review the role of tumor angiogenesis as the rationale for antiangiogenic therapy, the clinical data associated with ziv-aflibercept, and its current role as a treatment option compared to other antiangiogenic agents, such as bevacizumab and regorafenib. PMID:24368879

  3. 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

  4. [Current strategy in colorectal cancer screening].

    PubMed

    Lefter, L P; Dajbog, Elena; Scripcariu, V; Dragomir, Cr

    2005-01-01

    Screening programs should begin by classifying the individual patient's level of risk based on personal, family, and medical history, which will determine the appropriate approach for each subject. The individual's risk status determines when screening should be initiated and what tests and frequency are appropriate. To achieve these aims, care systems should establish standards and operating procedures. This review focuses on colorectal cancer screening methodology highlighting the latest available strategies. PMID:16610172

  5. 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 ...

  6. Variation in the Association Between Colorectal Cancer Susceptibility Loci and Colorectal Polyps by Polyp Type

    PubMed Central

    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.

    2014-01-01

    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. PMID:24875374

  7. Dendritic cell defects in the colorectal cancer

    PubMed Central

    Legitimo, Annalisa; Consolini, Rita; Failli, Alessandra; Orsini, Giulia; Spisni, Roberto

    2014-01-01

    Colorectal cancer (CRC) results from the accumulation of both genetic and epigenetic alterations of the genome. However, also the formation of an inflammatory milieu plays a pivotal role in tumor development and progression. Dendritic cells (DCs) play a relevant role in tumor by exerting differential pro-tumorigenic and anti-tumorigenic functions, depending on the local milieu. Quantitative and functional impairments of DCs have been widely observed in several types of cancer, including CRC, representing a tumor-escape mechanism employed by cancer cells to elude host immunosurveillance. Understanding the interactions between DCs and tumors is important for comprehending the mechanisms of tumor immune surveillance and escape, and provides novel approaches to therapy of cancer. This review summarizes updated information on the role of the DCs in colon cancer development and/or progression. PMID:25483675

  8. 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

  9. 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

  10. Primary prevention of colorectal cancer. The WHO Collaborating Centre for the Prevention of Colorectal Cancer.

    PubMed Central

    Shike, M.; Winawer, S. J.; Greenwald, P. H.; Bloch, A.; Hill, M. J.; Swaroop, S. V.

    1990-01-01

    Colorectal cancer is the third most common malignant neoplasm worldwide. Epidemiological and laboratory animal studies have established a link between various nutritional factors and the etiology of this cancer. Recent studies in genetic epidemiology and molecular biology have shown that inherited genetic factors also play an important role in colorectal carcinogenesis. Thus, genetic-nutritional interactions may form the basis for the development of this cancer. Nutritional factors that appear to promote or attenuate the carcinogenic process in the colon include fat, excess calories, fibre, calcium, selenium, and various vitamins. Strategies for primary prevention of colorectal cancer should therefore be targeted to all populations who are at risk because of dietary and hereditary predisposition. Based on current knowledge, recommended nutrition guidelines for reducing the risk of colon cancer include decreased fat consumption, adequate amounts of fruits, vegetables, and calcium, and avoidance of overweight. Research to further elucidate the role of diet in colorectal carcinogenesis should include randomized studies in humans, testing of various nutritional regimens, and the use of colonic adenomas and markers of cell proliferation and differentiation as end-points. PMID:2203551

  11. 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

  12. 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

  13. 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

  14. Colorectal cancer screening awareness among physicians in Greece

    PubMed Central

    Xilomenos, Apostolos; Mauri, Davide; Kamposioras, Konstantinos; Gkinosati, Athanasia; Zacharias, Georgios; Sidiropoulou, Varvara; Papadopoulos, Panagiotis; Chatzimichalis, Georgios; Golfinopoulos, Vassilis; Peponi, Christina

    2006-01-01

    Background Data comparison between SEER and EUROCARE database provided evidence that colorectal cancer survival in USA is higher than in European countries. Since adjustment for stage at diagnosis markedly reduces the survival differences, a screening bias was hypothesized. Considering the important role of primary care in screening activities, the purpose of the study was to investigate the colorectal cancer screening awareness among Hellenic physicians. Methods 211 primary care physicians were surveyed by mean of a self-reported prescription-habits questionnaire. Both physicians' colorectal cancer screening behaviors and colorectal cancer screening recommendations during usual check-up visits were analyzed. Results Only 50% of physicians were found to recommend screening for colorectal cancer during usual check-up visits, and only 25% prescribed cost-effective procedures. The percentage of physicians recommending stool occult blood test and sigmoidoscopy was 24% and 4% respectively. Only 48% and 23% of physicians recognized a cancer screening value for stool occult blood test and sigmoidoscopy. Colorectal screening recommendations were statistically lower among physicians aged 30 or less (p = 0.012). No differences were found when gender, level and type of specialization were analyzed, even though specialists in general practice showed a trend for better prescription (p = 0.054). Conclusion Contemporary recommendations for colorectal cancer screening are not followed by implementation in primary care setting. Education on presymptomatic control and screening practice monitoring are required if primary care is to make a major impact on colorectal cancer mortality. PMID:16756674

  15. 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. PMID:25996664

  16. Colonoscopy as a screening test for colorectal cancer.

    PubMed

    Schapira, M; Adler, M

    2005-01-01

    Colonoscopy is the current gold standard for the diagnosis and treatment of colorectal neoplasms. Several gastroenterological and/or endoscopical societies recommend screening by colonoscopy in high risk patients for colorectal cancer whilst for average risk patients colonoscopy remains a valid option. In some countries screening colonoscopy is now covered by medical insurance. It is also the final common pathway of all colorectal cancer screening methods. This paper addresses the advantages and also limitations of colonoscopy as the first procedure for colorectal screening and emphasizes the importance of organized training and continuous assessment of competence of gastroenterologists and the necessity to have quality control audits of the endoscopy units. PMID:16013645

  17. Anti-metastatic treatment in colorectal cancer: targeting signaling pathways.

    PubMed

    Lemos, Clara; Sack, Ulrike; Schmid, Felicitas; Juneja, Manisha; Stein, Ulrike

    2013-01-01

    Colorectal cancer is one of the most common cancers worldwide and one of the leading causes of cancer-related death in the Western world. Tumor progression towards metastasis affects a large number of patients with colorectal cancer and seriously affects their clinical outcome. Therefore, considerable effort has been made towards the development of therapeutic strategies that can decrease or prevent colorectal cancer metastasis. Standard treatment of metastatic colorectal cancer with chemotherapy has been improved in the last 10 years by the addition of new targeted agents. The currently used antibodies bevacizumab, cetuximab and panitumumab target the VEGF and EGFR signaling pathways, which are crucial for tumor progression and metastasis. These antibodies have shown relevant efficacy in both first- and second-line treatment of metastatic colorectal cancer. Additionally, other signaling pathways, including the Wnt and HGF/Met pathways, have a well-established role in colorectal cancer progression and metastasis and constitute, therefore, promising targets for new therapeutic approaches. Several new drugs targeting these pathways, including different antibodies and small-molecule tyrosine kinase inhibitors, are currently being developed and tested in clinical trials. In this review, we summarize the new developments in this field, focusing on the inhibitors that show more promising results for use in colorectal cancer patients. PMID:22973955

  18. 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

  19. 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

  20. GREM1 and POLE variants in hereditary colorectal cancer syndromes.

    PubMed

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

    2016-01-01

    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. PMID:26493165

  1. Colorectal cancer development and advances in screening.

    PubMed

    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

  2. Targeting Notch Signaling in Colorectal Cancer

    PubMed Central

    Suman, Suman; Das, Trinath P.; Ankem, Murali K.; Damodaran, Chendil

    2014-01-01

    The activation of Notch signaling is implicated in tumorigenesis in the colon due to the induction of pro-survival signaling in colonic epithelial cells. Chemoresistance is a major obstacle for treatment and for the complete eradication of colorectal cancer (CRC), hence, the inhibition of Notch is an attractive target for CRC and several groups are working to identify small molecules or monoclonal antibodies that inhibit Notch or its downstream events; however, toxicity profiles in normal cells and organs often impede the clinical translation of these molecules. Dietary agents have gained momentum for targeting several pro-survival signaling cascades, and recent studies demonstrated that agents that inhibit Notch signaling result in growth inhibition in preclinical models of CRC. In this review, we focus on the importance of Notch as a preventive and therapeutic target for colon cancer and on the effect of WA on this signaling pathway in the context of colon cancer. PMID:25395896

  3. Targeting Notch Signaling in Colorectal Cancer.

    PubMed

    Suman, Suman; Das, Trinath P; Ankem, Murali K; Damodaran, Chendil

    2014-12-01

    The activation of Notch signaling is implicated in tumorigenesis in the colon due to the induction of pro-survival signaling in colonic epithelial cells. Chemoresistance is a major obstacle for treatment and for the complete eradication of colorectal cancer (CRC), hence, the inhibition of Notch is an attractive target for CRC and several groups are working to identify small molecules or monoclonal antibodies that inhibit Notch or its downstream events; however, toxicity profiles in normal cells and organs often impede the clinical translation of these molecules. Dietary agents have gained momentum for targeting several pro-survival signaling cascades, and recent studies demonstrated that agents that inhibit Notch signaling result in growth inhibition in preclinical models of CRC. In this review, we focus on the importance of Notch as a preventive and therapeutic target for colon cancer and on the effect of WA on this signaling pathway in the context of colon cancer. PMID:25395896

  4. 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

  5. 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.

  6. Inflammation and chemerin in colorectal cancer.

    PubMed

    Erdogan, Serpil; Yilmaz, Fatma Meric; Yazici, Ozan; Yozgat, Ahmet; Sezer, Sevilay; Ozdemir, Nuriye; Uysal, Sema; Purnak, Tugrul; Sendur, Mehmet Ali; Ozaslan, Ersan

    2016-05-01

    Chemerin is expressed mainly in the adipose tissue. It is an agonist of chemokine-like receptor-1, which is expressed by the immune system cells. Chemerin stimulates the chemotaxis of the immune system cells, and this indicates the function of chemerin and chemokine-like receptor-1 in the immune response. The tumor microenvironment is very important for determining cancer cell growth and spreading. Therefore, we aimed to investigate the association between colorectal cancer, inflammation, and adipokines including chemerin, adiponectin, and vaspin. The study group consisted of patients with colon cancer, whereas the control subjects consisted of patients with benign conditions, diagnosed with colonoscopy. The two groups were compared in terms of the C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen, adiponectin, chemerin, and vaspin. A total of 41 (28 men, 13 women) patients with confirmed colon cancer, and 27 (15 men, 12 women) controls without, confirmed by colonoscopy, were enrolled. The median chemerin levels were found significantly higher in the study group than the controls (390 vs. 340 ng/mL, p = 0.032), whereas the mean vaspin and adiponectin levels were not significantly different. The median values for the CRP, fibrinogen, and ESR were significantly higher in the patients with colon cancer, when compared to the control group (6.08 vs. 1.4 mg/L, p < 0.0001; 408 vs. 359 mg/dL, p = 0.002; and 30 vs. 8 mm/h, p < 0.0001, respectively). Our results show that higher levels of circulating chemerin, CRP, fibrinogen, and ESR are associated with an increased risk of developing colorectal cancer. PMID:26628300

  7. Eastern Canadian Colorectal Cancer Consensus Conference 2013: emerging therapies in the treatment of pancreatic, rectal, and colorectal cancers.

    PubMed

    Di Valentin, T; Asmis, T; Asselah, J; Aubin, F; Aucoin, N; Berry, S; Biagi, J; Booth, C M; Burkes, R; Coburn, N; Colwell, B; Cripps, C; Dawson, L A; Dorreen, M; Frechette, D; Goel, R; Gray, S; Hammad, N; Jonker, D; Kavan, P; Maroun, J; Nanji, S; Roberge, D; Samson, B; Seal, M; Shabana, W; Simunovic, M; Snow, S; Tehfe, M; Thirlwell, M; Tsvetkova, E; Vickers, M; Vuong, T; Goodwin, R

    2016-02-01

    The annual Eastern Canadian Colorectal Cancer Consensus Conference held in Montreal, Quebec, 17-19 October 2013, marked the 10-year anniversary of this meeting that is attended by leaders in medical, radiation, and surgical oncology. The goal of the attendees is to improve the care of patients affected by gastrointestinal malignancies. Topics discussed during the conference included pancreatic cancer, rectal cancer, and metastatic colorectal cancer. PMID:26966404

  8. Eastern Canadian Colorectal Cancer Consensus Conference 2013: emerging therapies in the treatment of pancreatic, rectal, and colorectal cancers

    PubMed Central

    Di Valentin, T.; Asmis, T.; Asselah, J.; Aubin, F.; Aucoin, N.; Berry, S.; Biagi, J.; Booth, C.M.; Burkes, R.; Coburn, N.; Colwell, B.; Cripps, C.; Dawson, L.A.; Dorreen, M.; Frechette, D.; Goel, R.; Gray, S.; Hammad, N.; Jonker, D.; Kavan, P.; Maroun, J.; Nanji, S.; Roberge, D.; Samson, B.; Seal, M.; Shabana, W.; Simunovic, M.; Snow, S.; Tehfe, M.; Thirlwell, M.; Tsvetkova, E.; Vickers, M.; Vuong, T.; Goodwin, R.

    2016-01-01

    The annual Eastern Canadian Colorectal Cancer Consensus Conference held in Montreal, Quebec, 17–19 October 2013, marked the 10-year anniversary of this meeting that is attended by leaders in medical, radiation, and surgical oncology. The goal of the attendees is to improve the care of patients affected by gastrointestinal malignancies. Topics discussed during the conference included pancreatic cancer, rectal cancer, and metastatic colorectal cancer. PMID:26966404

  9. 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

  10. Temporal Trends in Colorectal Cancer Screening among Asian Americans.

    PubMed

    Fedewa, Stacey A; Sauer, Ann Goding; Siegel, Rebecca L; Smith, Robert A; Torre, Lindsey A; Jemal, Ahmedin

    2016-06-01

    Asian Americans (AA) are less likely to be screened for colorectal cancer compared with non-Hispanic Whites (NHW), with a widening disparity for some AA subgroups in the early 2000s. Whether these patterns have continued in more recent years is unknown. We examined temporal trends in colorectal cancer screening among AA overall compared with NHWs and by AA subgroup (Chinese, Japanese, Korean, Filipino, South Asian, Vietnamese) using data from the 2003, 2005, 2007, and 2009 California Health Interview Surveys. Unadjusted (PR) and adjusted (aPR) prevalence ratios for colorectal cancer screening, accounting for sociodemographic, health care, and acculturation factors, were calculated for respondents ages 50 to 75 years (NHW n = 60,125; AA n = 6,630). Between 2003 and 2009, colorectal cancer screening prevalence increased from 43.3% to 64.6% in AA (P ≤ 0.001) and from 58.1% to 71.4% in NHW (P ≤ 0.001). Unadjusted colorectal cancer screening was significantly lower among AA compared with NHW in 2003 [PR = 0.74; 95% confidence interval (CI), 0.68-0.82], 2005 (PR = 0.78; 95% CI, 0.72-0.84), 2007 (PR = 0.91; 95% CI, 0.85-0.96), and 2009 (PR = 0.90; 95% CI, 0.84-0.97), though disparities narrowed over time. After adjustment, there were no significant differences in colorectal cancer screening between the two groups, except in 2003. In subgroup analyses, between 2003 and 2009, colorectal cancer screening significantly increased by 22% in Japanese, 56% in Chinese, 47% in Filipino, and 94% in Koreans. In our study of California residents, colorectal cancer screening disparities between AA and NHW narrowed, but were not eliminated and screening prevalence among AA remains below nationwide goals, including the Healthy People 2020 goal of increasing colorectal cancer screening prevalence to 70.5%. Cancer Epidemiol Biomarkers Prev; 25(6); 995-1000. ©2016 AACR. PMID:27197273

  11. The association between serum ferritin with colorectal cancer

    PubMed Central

    Feng, Zhe; Chen, Ji-Wei; Feng, Jian-Hua; Shen, Fei; Cai, Wen-Song; Cao, Jie; Xu, Bo

    2015-01-01

    There are conflicting reports on the correlation between serum levels of ferritin with colorectal cancer. The purpose of the present study is to clarify the association between serum ferritin with colorectal cancer using a meta-analysis approach. We searched articles indexed in Pubmed published as of July 2015 that met our predefined criteria. Six eligible articles involving 927 subjects were identified. Overall, pooled analysis indicated that subjects with colorectal cancer had lower serum level of ferritin than the healthy controls (SMD=-1.569, 95% CI=[-2.718, -0.420], P= 0.007). Further subgroup analysis found lower serum level of ferritin among patients with colorectal cancer in eastern country (SMD=-1.956, 95% CI=[-3.750, -0.162], P=0.033), but not in western country (SMD=-1.285, 95% CI=[-2.778, 0.207], P=0.091). In conclusion, this meta-analysis supports a significant association between serum ferritin with colorectal cancer. However, the subgroup analysis found that there was significant effect modification of ferritin level by ethnic. Thus this finding needs further confirmation by trans-regional multicenter, long-term observation in a cohort design to obtain better understanding of causal relationships between serum ferrintin levels and colorectal cancer, through measuring ferritin at baseline to investigate whether the highest ferritin category versus lowest is associated with colorectal cancer risk. PMID:26885206

  12. Most Patients with Colorectal Tumors at Young Age Do Not Visit a Cancer Genetics Clinic

    PubMed Central

    Overbeek, Lucia I. H.; Hoogerbrugge, Nicoline; van Krieken, Joannes H. J. M.; Nagengast, Fokko M.; Ruers, Theo J. M.; Ligtenberg, Marjolijn J. L.

    2008-01-01

    Purpose This study examined the referral process for genetic counseling at a cancer genetics clinic in patients with colorectal cancer and to search for determinants of variation in this referral process. Methods Patients who were recently diagnosed with colorectal cancer at a young age or multiple cancers associated with Lynch syndrome, hereditary nonpolyposis colorectal cancer, (N = 119) were selected from PALGA, the nationwide network and registry of histopathology and cytopathology in the Netherlands. In a retrospective analysis, we examined whether these patients visited a cancer genetics clinic and identified determinants for referral to such a clinic. Factors of patients, professional practice, and hospital setting were explored with logistic regression modeling. Results Thirty-six (30 percent) patients visited a cancer genetics clinic. Seventy percent of patients whom the surgeon referred to a cancer genetics clinic decided to visit such a clinic. Analysis of determinants showed that patients with whom the surgeon discussed referral and that were treated in a teaching hospital were more likely to visit a cancer genetics clinic. Conclusion The referral process is not optimally carried out. To deliver optimal care for patients suspected of hereditary colorectal cancer, this process must be improved with interventions focusing on patient referral by surgeons and raising awareness in nonteaching hospitals. PMID:18536968

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

    PubMed Central

    Woo, Hae Dong; Kim, Jeongseon

    2013-01-01

    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. PMID:23467443

  14. 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

  15. 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

  16. The Expression of Multiple Proteins as Prognostic Factors in Colorectal Cancer: Cathepsin D, p53, COX-2, Epidermal Growth Factor Receptor, C-erbB-2, and Ki-67

    PubMed Central

    Shin, Il Yong; Sung, Na Young; Lee, Youn Soo; Kwon, Taek Soo; Si, Yoon; Lee, Yoon Suk; Oh, Seong Taek

    2014-01-01

    Background/Aims A single gene mutation alone cannot explain the poor prognosis of colorectal cancer. This study aimed to establish a correlation between the expression of six proteins and the prognosis of colorectal cancer patients. Methods Tissue samples were collected from 266 patients who underwent surgery for colorectal cancer at our institution from January 2006 to December 2007. The expression of six proteins were determined using immunohistochemical staining of specimens. Results Cathepsin D, p53, COX-2, epidermal growth factor receptor, c-erbB-2, and Ki-67 expression were detected in 38.7%, 60.9%, 37.6%, 35.7%, 30.1%, and 74.4% of the samples, respectively. The expression of cathepsin D was significantly correlated with reduced cancer-free survival (p=0.036) and colorectal cancer-specific survival (p=0.003), but the other expression levels were not. In a multivariate analysis, cathepsin D expression was found to be an independent prognostic factor for poorer colorectal cancer-specific survival (hazard ratio, 8.55; 95% confidence interval, 1.07 to 68.49). Furthermore, patients with tumors expressing four or more of the proteins had a significantly decreased cancer-free survival rate (p=0.006) and colorectal cancer-specific survival rate (p=0.002). Conclusions Patients with cathepsin D positivity had a poorer outcome than patients who were cathepsin D-negative. Thus, cathepsin D may provide an indicator for appropriate intensive follow-up and adjuvant chemotherapy. PMID:24516696

  17. Dendritic Cells in Colorectal Cancer and a Potential for their Use in Therapeutic Approaches.

    PubMed

    Chistiakov, Dimitry A; Orekhov, Alexander N; Bobryshev, Yuri V

    2016-01-01

    Multiple pathogenic mechanisms contribute to the development of colorectal cancer. This tumor is characterized by high chemoresistance and low immunogenicity due to the effective mechanisms of immunosuppression. Dendritic cells (DCs) play a key role in recognition of tumor antigens and induction of T-cell-primed anticancer response. However, in cancer microenvironment, the function of tumor-infiltrating DCs becomes impaired and switched from the immunostimulation to the immunosuppression. Colorectal cancer cells express anti-inflammatory cytokines such as IL-10 and TGF-β that could affect DC phenotype and support tumor escape from the immune surveillance. As a result, tumor-associated DCs display numerous defects in antigen-presenting capacity and have an altered pattern of expression of immune costimulatory molecules towards the immunoregulatory phenotype. Indeed, understanding of mechanisms, such as how tumor could impair activity of DCs, would help in the development of new DC-based vaccines against colorectal cancer. PMID:26845127

  18. 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

  19. Colorectal cancer: Metastases to a single organ

    PubMed Central

    Vatandoust, Sina; Price, Timothy J; Karapetis, Christos S

    2015-01-01

    Colorectal cancer (CRC) is a common malignancy worldwide. In CRC patients, metastases are the main cause of cancer-related mortality. In a group of metastatic CRC patients, the metastases are limited to a single site (solitary organ); the liver and lungs are the most commonly involved sites. When metastatic disease is limited to the liver and/or lungs, the resectability of the metastatic lesions will dictate the management approach and the outcome. Less commonly, the site of solitary organ CRC metastasis is the peritoneum. In these patients, cytoreduction followed by hyperthermic intraperitoneal chemotherapy may improve the outcome. Rarely, CRC involves other organs, such as the brain, bone, adrenals and spleen, as the only site of metastatic disease. There are limited data to guide clinical practice in these cases. Here, we have reviewed the disease characteristics, management approaches and prognosis based on the metastatic disease site in patients with CRC with metastases to a single organ. PMID:26557001

  20. 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. PMID:27048903

  1. Immune checkpoints and immunotherapy for colorectal cancer

    PubMed Central

    Singh, Preet Paul; Sharma, Piyush K.; Krishnan, Gayathri; Lockhart, A. Craig

    2015-01-01

    Colorectal cancer (CRC) remains one of the major causes of death worldwide, despite steady improvement in early detection and overall survival over the past decade. Current treatment paradigms, with chemotherapy and biologics, appear to have reached their maximum benefit. Immunotherapy, especially with checkpoint inhibitors, has shown considerable clinical benefit in various cancers, including mismatch-repair-deficient CRC. This has led to the planning and initiation of several clinical trials evaluating novel immunotherapy agents—as single agents, combinations and in conjunction with chemotherapy—in patients with CRC. This article reviews biological and preclinical data for checkpoint inhibitors and discusses various immunotherapy trials in CRC, as well as current efforts in CRC immunotherapy. PMID:26510455

  2. 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

  3. [Biotherapies in metastatic colorectal cancers in 2014].

    PubMed

    Jouinot, Anne; Coriat, Romain; Huillard, Olivier; Goldwasser, François

    2014-10-01

    The treatment of metastatic colorectal cancer has been transformed during the last decade with biotherapies, two of them were marketed in 2013. Four agents are monoclonal antibodies, while the fifth agent is a tyrosine kinase inhibitor. Two agents are inhibitors of the EGF-receptor pathway, cetuximab and panitumumab, and have as class-toxicity, cutaneous toxicity. The other three agents are bevacizumab, aflibercept and regorafenib, and interact with angiogenesis, they are associated with a risk of vascular toxicity, mainly hypertension. These agents participate to an improvement of disease control at the metastatic stage, and in some cases, favour the curative surgical resection of metastases. Their use is discussed in multidisciplinary meetings dedicated to gastrointestinal cancers, in the presence of liver surgeons. PMID:25065664

  4. Prognostic Value of Colorectal Cancer Biomarkers

    PubMed Central

    Bianchi, Paolo; Laghi, Luigi; Delconte, Gabriele; Malesci, Alberto

    2011-01-01

    Despite the large amount of data in cancer biology and many studies into the likely survival of colorectal cancer (CRC) patients, knowledge regarding the issue of CRC prognostic biomarkers remains poor. The Tumor-Node-Metastasis (TNM) staging system continues to be the most powerful and reliable predictor of the clinical outcome of CRC patients. The exponential increase of knowledge in the field of molecular genetics has lead to the identification of specific alterations involved in the malignant progression. Many of these genetic alterations were proposed as biomarkers which could be used in clinical practice to estimate CRC prognosis. Recently there has been an explosive increase in the number of putative biomarkers able to predict the response to specific adjuvant treatment. In this review we explore and summarize data concerning prognostic and predictive biomarkers and we attempt to shed light on recent research that could lead to the emergence of new biomarkers in CRC. PMID:24212797

  5. 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

  6. [Colorectal cancer endometriosis resembling stenosing extrapelvic: report of two cases].

    PubMed

    Gallardo Arteaga, Josué; Marin Calderón, Luis; Barboza Beraun, Aurelio; Rivas Wong, Luz; Frisancho Velarde, Oscar

    2012-01-01

    We present two women of 40 and 42 years with colorectal endometriosis, both with a history of pelvic endometriosis and simultaneous episodes of rectal bleeding with menstruation. In endoscopic evaluations detected a sigmoid tumor and rectosigmoid tumor respectively, which apparently corresponds to stenosing colorectal cancer of epithelial origin. PMID:23307093

  7. [Hereditary non-polyposis colorectal cancer. Report of four siblings].

    PubMed

    Zárate, Alejandro; Alvarez, Karin; Wielandt, Ana María; Hevia, Montserrat; De la Fuente, Marjorie; Carvallo, Pilar; López-Köstner, Francisco

    2008-06-01

    Hereditary non-polyposis colorectal cancer (HNPCC) or Lynch Syndrome is an autosomic dominant syndrome involving 596-1096 of colorectal cancer patients. Mutations in MLH1 and MSH2 genes account for most cases. These two genes participate in the DNA mismatch repair pathway. Therefore mutation carriers show microsatellite instability (MSI) in tumors. This syndrome is characterized by the early development of colorectal cancer (before 50 years) and an increased incidence of cancer in other organs. We report four siblings from a family diagnosed with HNPCC. All of them were subjected to colonic surgery for colorectal cancer Moreover, one patient developed an ampulloma after her colon surgery. The molecular-genetic analysis revealed three brothers with microsatellite instability in the tumor tissue, the absence of the MLH1 protein, and the presence of a germ line mutation localized in introm 15 of the MLH1 gene. PMID:18769833

  8. The Struggle Within: Microbial Influences on Colorectal Cancer

    PubMed Central

    Arthur, Janelle C.; Jobin, Christian

    2012-01-01

    Recently, an unprecedented effort has been directed at understanding the interplay between chronic inflammation and development of cancer, with the case of inflammatory bowel disease (IBD)-associated colorectal cancer at the forefront of this research endeavor. The last decade has been particularly fertile, with the discovery of numerous innovative paradigms linking various inflammatory, proliferative, and innate and adaptive immune signaling pathways to the development of colorectal cancer. Because of the preponderant role of the intestinal microbiota in the initiation and progression of IBD, recent efforts have been directed at understanding the relationship between bacteria and colorectal cancer. The microbiota and its collective genome, the microbiome, form a diverse and complex ecological community that profoundly impacts intestinal homeostasis and disease states. This review will discuss the differential influence of the microbiota on the development of IBD-associated colorectal cancer and highlight the role of innate immune sensor-dependent as well as -independent mechanisms in this pathology. PMID:20848537

  9. 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

  10. 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

  11. Preoperative radiotherapy for colorectal cancer.

    PubMed Central

    Higgins, G A; Conn, J H; Jordan, P H; Humphrey, E W; Roswit, B; Keehn, R J

    1975-01-01

    In a prospective randomized trial, 700 patients with a confirmed histological diagnosis of adenocarcinoma of the rectum or rectosigmoid were randomized to receive radiotherapy prior to operation (2000 to 2500 rads in two weeks) or surgery alone. Five year observed survival in the 453 patients on whom "curative" resection was possible was 48.5% in the X-ray treated group compared with 38.8% in controls, while in the 305 having low lying lesions requiring abdominoperineal resection, survival in the treated group was 46.9% compared with 34.3% in controls. Although suggestive of a treatment benefit, neither is considered statistically significant. Histologically positive lymph nodes were found in 41.2% of the control group and in only 27.8% of the patients receiving radiotherapy. Reveiw of all patients who died during the study shows a consistently lower death rate from cancer in the radiotherapy group. Although this study suggests a treatment benefit from preoperative radiotherapy, further studies now in progress by this group and others are necessary to determine the optimal dose regimen. PMID:805571

  12. 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

  13. Chemotherapy for colorectal cancer in the elderly

    PubMed Central

    Kim, Jung Han

    2015-01-01

    Colorectal cancer (CRC) is one of the leading causes of cancer-related death in the elderly. However, elderly patients with CRC tend to be under-presented in clinical trials and undertreated in clinical practice. Advanced age alone should not be the only criteria to preclude effective therapy in elderly patients with CRC. The best guide about optimal cancer treatment can be provided by comprehensive geriatric assessment. Elderly patients with stage III colon cancer can enjoy the same benefit from adjuvant chemotherapy with 5-fluorouracil/leucovorin or capecitabine as younger patients, without a substantial increase in toxicity. With conflicting results of retrospective studies and a lack of data available from randomized studies, combined modality treatment should be used with great caution in elderly patients with locally advanced rectal cancer. Combination chemotherapy can be considered for older patients with metastatic CRC. For elderly patients who are frail or vulnerable, however, monotherapy or a stop-and-go strategy may be desirable. The use of targeted therapies in older patients with metastatic CRC appears to be promising in view of their better efficacy and toxicity. Treatment should be individualized based on the nature of the disease, the physiologic or functional status, and the patient’s preference. PMID:25954089

  14. Estrogen Plus Progestin and Colorectal Cancer Incidence and Mortality

    PubMed Central

    Simon, Michael S.; Chlebowski, Rowan T.; Wactawski-Wende, Jean; Johnson, Karen C.; Muskovitz, Andrew; Kato, Ikuko; Young, Alicia; Hubbell, F. Allan; Prentice, Ross L.

    2012-01-01

    Purpose During the intervention phase in the Women's Health Initiative (WHI) clinical trial, use of estrogen plus progestin reduced the colorectal cancer diagnosis rate, but the cancers were found at a substantially higher stage. To assess the clinical relevance of the findings, analyses of the influence of combined hormone therapy on colorectal cancer incidence and colorectal cancer mortality were conducted after extended follow-up. Patients and Methods The WHI study was a randomized, double-blind, placebo-controlled clinical trial involving 16,608 postmenopausal women with an intact uterus who were randomly assigned to daily 0.625 mg conjugated equine estrogen plus 2.5 mg medroxyprogesterone acetate (n = 8,506) or matching placebo (n = 8,102). Colorectal cancer diagnosis rates and colorectal cancer mortality were assessed. Results After a mean of 5.6 years (standard deviation [SD], 1.03 years) of intervention and 11.6 years (SD, 3.1 years) of total follow-up, fewer colorectal cancers were diagnosed in the combined hormone therapy group compared with the placebo group (diagnoses/year, 0.12% v 0.16%; hazard ratio [HR], 0.72; 95% CI, 0.56 to 0.94; P = .014). Bowel screening examinations were comparable between groups throughout. Cancers in the combined hormone therapy group more commonly had positive lymph nodes (50.5% v 28.6%; P < .001) and were at higher stage (regional or distant, 68.8% v 51.4%; P = .003). Although not statistically significant, there was a higher number of colorectal cancer deaths in the combined hormone therapy group (37 v 27 deaths; 0.04% v 0.03%; HR, 1.29; 95% CI, 0.78 to 2.11; P = .320). Conclusion The findings, suggestive of diagnostic delay, do not support a clinically meaningful benefit for combined hormone therapy on colorectal cancer. PMID:23008295

  15. Colorectal Cancer Screening: Stool DNA and Other Noninvasive Modalities

    PubMed Central

    Bailey, James R.; Aggarwal, Ashish; Imperiale, Thomas F.

    2016-01-01

    Colorectal cancer screening dates to the discovery of pre-cancerous adenomatous tissue. Screening modalities and guidelines directed at prevention and early detection have evolved and resulted in a significant decrease in the prevalence and mortality of colorectal cancer via direct visualization or using specific markers. Despite continued efforts and an overall reduction in deaths attributed to colorectal cancer over the last 25 years, colorectal cancer remains one of the most common causes of malignancy-associated deaths. In attempt to further reduce the prevalence of colorectal cancer and associated deaths, continued improvement in screening quality and adherence remains key. Noninvasive screening modalities are actively being explored. Identification of specific genetic alterations in the adenoma-cancer sequence allow for the study and development of noninvasive screening modalities beyond guaiac-based fecal occult blood testing which target specific alterations or a panel of alterations. The stool DNA test is the first noninvasive screening tool that targets both human hemoglobin and specific genetic alterations. In this review we discuss stool DNA and other commercially available noninvasive colorectal cancer screening modalities in addition to other targets which previously have been or are currently under study. PMID:26934885

  16. Germline EPHB2 Receptor Variants in Familial Colorectal Cancer

    PubMed Central

    Zogopoulos, George; Jorgensen, Claus; Bacani, Julinor; Montpetit, Alexandre; Lepage, Pierre; Ferretti, Vincent; Chad, Lauren; Selvarajah, Subani; Zanke, Brent; Hudson, Thomas J.; Pawson, Tony; Gallinger, Steven

    2008-01-01

    Familial clustering of colorectal cancer occurs in 15–20% of cases, however recognized cancer syndromes explain only a small fraction of this disease. Thus, the genetic basis for the majority of hereditary colorectal cancer remains unknown. EPHB2 has recently been implicated as a candidate tumor suppressor gene in colorectal cancer. The aim of this study was to evaluate the contribution of EPHB2 to hereditary colorectal cancer. We screened for germline EPHB2 sequence variants in 116 population-based familial colorectal cancer cases by DNA sequencing. We then estimated the population frequencies and characterized the biological activities of the EPHB2 variants identified. Three novel nonsynonymous missense alterations were detected. Two of these variants (A438T and G787R) result in significant residue changes, while the third leads to a conservative substitution in the carboxy-terminal SAM domain (V945I). The former two variants were found once in the 116 cases, while the V945I variant was present in 2 cases. Genotyping of additional patients with colorectal cancer and control subjects revealed that A438T and G787R represent rare EPHB2 alleles. In vitro functional studies show that the G787R substitution, located in the kinase domain, causes impaired receptor kinase activity and is therefore pathogenic, whereas the A438T variant retains its receptor function and likely represents a neutral polymorphism. Tumor tissue from the G787R variant case manifested loss of heterozygosity, with loss of the wild-type allele, supporting a tumor suppressor role for EPHB2 in rare colorectal cancer cases. Rare germline EPHB2 variants may contribute to a small fraction of hereditary colorectal cancer. PMID:18682749

  17. 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

  18. 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

  19. [Panitumumab-treatment of metastatic colorectal cancer].

    PubMed

    Pikó, Béla

    2009-06-01

    In the molecular target treatment strategy of metastatic colorectal cancer patients panitumumab represents a new class of drugs due to its fully human nature, and no need for premedication and loading dose. Panitumumab binds to epidermal growth factor receptor (EGFR) selectively. In registration pivotal studies the analysis of patient subgroups for KRAS status gives strong evidence for the important role of RAS oncogene: median progression-free survival was 16 weeks on panitumumab arm in KRAS wild-type patients (8 weeks in best supportive care), while in KRAS mutant patients panitumumab showed no efficacy, however adverse events were more frequent and severe. According to SmPC, panitumumab is indicated as monotherapy for the treatment of patients with EGFR expressing metastatic colorectal carcinoma with non-mutated (wild-type) KRAS after failure of fluoropyrimidine-, oxaliplatin- , and irinotecan-containing chemotherapy regimens. Adverse events are similar as with other EGFR inhibitors: skin symptoms (rash), lung infiltrates, diarrhoea, ion abnormalities of renal origin. The drug was formerly available via named patient reimbursement, and now is financed by diagnosis-related group (DRG) system. PMID:19581179

  20. [Regorafenib in patients with metastatic colorectal cancer: a review and an update].

    PubMed

    Zaniboni, Alberto; Mansueto, Giovanni

    2015-12-01

    Standard chemotherapy in patients with metastatic colorectal cancer is based on a combination of fluoropyrimidines, irinotecan and oxaliplatin. Regorafenib, an oral multikynase inhibitor blocking multiple disease progression-involved pathways, is a new therapeutic option in patients who already received standard therapy. In a phase III randomized, placebo-controlled study regorafenib, as compared to best supportive care, showed a statistically significant improvement in overall survival, irrespective of KRAS mutation status. Safety profile of regorafenib is acceptable, with few severe grade adverse events which can be adequately managed within few weeks after treatment beginning. Regorafenib is a new treatment standard in patients who already received chemotherapy for metastatic colorectal cancer. PMID:26780072

  1. 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

  2. Colorectal cancer in asbestos cement workers in Denmark.

    PubMed

    Raffn, E; Villadsen, E; Lynge, E

    1996-09-01

    Recent data on the risk of colorectal cancer following exposure to chrysotile are conflicting. We report on colorectal cancer morbidity in a large cohort of asbestos cement workers from Denmark mainly exposed to chrysotile. The total cohort had an SIR of 1.23 (95% CI 1.01-1.48). With a latency period of 15 years, men employed in the early (1928-1950) production period had an SIR of 1.47 (95% CI 1.05-2.01). With the observation of excess risks of colorectal cancer morbidity among chrysotile exposed asbestos cement workers in both Sweden and Denmark the question on the role of chrysotile in the etiology of colorectal cancer remains open. PMID:8876793

  3. Body mass index and risk of colorectal cancer according to tumor lymphocytic infiltrate.

    PubMed

    Hanyuda, Akiko; Ogino, Shuji; Qian, Zhi Rong; Nishihara, Reiko; Song, Mingyang; Mima, Kosuke; Inamura, Kentaro; Masugi, Yohei; Wu, Kana; Meyerhardt, Jeffrey A; Chan, Andrew T; Fuchs, Charles S; Giovannucci, Edward L; Cao, Yin

    2016-08-15

    Higher body mass index (BMI), higher body adiposity and obesity have been associated with increased risk of colorectal cancer. Evidence suggests that excess energy balance may influence systemic immune and inflammatory status. Thus, we hypothesized that the positive association between BMI and colorectal cancer risk might differ according to colorectal carcinoma subtypes according to levels of histopathological lymphocytic reaction to tumor. We collected biennial questionnaire data on weight and baseline height information in two prospective cohort studies, the Nurses' Health Study (1980-2010) and the Health Professionals Follow-up Study (1986-2010). Utilizing duplication-method Cox proportional hazards regression models, we prospectively assessed the association between BMI and risk of colorectal cancer subtypes according to the degree of Crohn's-like lymphoid reaction, peritumoral lymphocytic reaction, intratumoral periglandular reaction, tumor-infiltrating lymphocytes, the overall lymphocytic reaction score, or T-cell [CD3(+) , CD8(+) , CD45RO (PTPRC)(+) or FOXP3(+) ] density in tumor tissue. Statistical significance level was adjusted for multiple hypotheses testing by Bonferroni correction. During follow up of 1,708,029 men and women (over 3,346,752 person-years), we documented 1,436 incident rectal and colon cancer cases with available formalin-fixed paraffin-embedded tumor tissue materials and pathological immunity data. BMI was significantly associated with higher risk of overall colorectal cancer (Ptrend  < 0.001); however, the association of BMI with colorectal carcinoma risk did not significantly differ by the level of lymphocytic reaction or T-cell infiltration in tumor tissue status (Pheterogeneity  > 0.10). BMI may be associated with risk of colorectal cancer regardless of levels of lymphocytic response to tumor. PMID:27037951

  4. Racial Disparities in Stage-Specific Colorectal Cancer Mortality: 1960–2005

    PubMed Central

    Iyer, Shally Shalini; Armstrong, Katrina; Asch, David A.

    2010-01-01

    Objectives. We examined whether racial disparities in stage-specific colorectal cancer survival changed between 1960 and 2005. Methods. We used US Mortality Multiple-Cause-of-Death Data Files and intercensal estimates to calculate standardized mortality rates by gender and race from 1960 to 2005. We used Surveillance, Epidemiology, and End Results (SEER) data to estimate stage-specific colorectal cancer survival. To account for SEER sampling uncertainty, we used a bootstrap resampling procedure and fit a Cox proportional hazards model. Results. Between 1960–2005, patterns of decline in mortality rate as a result of colorectal cancer differed greatly by gender and race: 54% reduction for White women, 14% reduction for Black women, 39% reduction for White men, and 28% increase for Black men. Blacks consistently experienced worse rates of stage-specific survival and life expectancy than did Whites for both genders, across all age groups, and for localized, regional, and distant stages of the disease. Conclusions. The rates of stage-specific colorectal cancer survival differed among Blacks when compared with Whites during the 4-decade study period. Differences in stage-specific life expectancy were the result of differences in access to care or quality of care. More attention should be given to racial disparities in colorectal cancer management. PMID:20724684

  5. Natural history of hepatic metastases from colorectal cancer - pathobiological pathways with clinical significance

    PubMed Central

    Paschos, Konstantinos A; Majeed, Ali W; Bird, Nigel C

    2014-01-01

    Colorectal cancer hepatic metastases represent the final stage of a multi-step biological process. This process starts with a series of mutations in colonic epithelial cells, continues with their detachment from the large intestine, dissemination through the blood and/or lymphatic circulation, attachment to the hepatic sinusoids and interactions with the sinusoidal cells, such as sinusoidal endothelial cells, Kupffer cells, stellate cells and pit cells. The metastatic sequence terminates with colorectal cancer cell invasion, adaptation and colonisation of the hepatic parenchyma. All these events, termed the colorectal cancer invasion-metastasis cascade, include multiple molecular pathways, intercellular interactions and expression of a plethora of chemokines and growth factors, and adhesion molecules, such as the selectins, the integrins or the cadherins, as well as enzymes including matrix metalloproteinases. This review aims to present recent advances that provide insights into these cell-biological events and emphasizes those that may be amenable to therapeutic targeting. PMID:24744570

  6. 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

  7. Colorectal Cancer Screening in 3 Racial Groups

    PubMed Central

    Kelly, Kimberly M.; Dickinson, Stephanie L.; DeGraffinreid, Cecilia R.; Tatum, Cathy M.; Paskett, Electra D.

    2015-01-01

    Objectives To understand predictors of colorectal cancer (CRC) screening in African Americans, European Americans, and Native Americans as these groups differ in CRC incidence and mortality. Methods Participants were surveyed for knowledge, beliefs, and behaviors related to CRC. Results Predictive regression modeling found, after adjusting for race, CRC risk, and CRC worry, the odds of screening within guidelines were increased for men, those receiving doctor’s recommendation, those with polyp/tumor history, those under 70, those with more knowledge about CRC, and those with fewer barriers to screening. CRC screening rates did not differ by race. Conclusions These results reiterate the importance of knowledge, barriers, and physician recommendation for CRC screening in all racial groups. PMID:17555381

  8. The Consensus Molecular Subtypes of Colorectal Cancer

    PubMed Central

    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

    2015-01-01

    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 (CMS) with distinguishing features: CMS1 (MSI Immune, 14%), hypermutated, microsatellite unstable, strong immune activation; CMS2 (Canonical, 37%), epithelial, chromosomally unstable, marked WNT and MYC signaling activation; CMS3 (Metabolic, 13%), epithelial, 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 intra-tumoral 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. PMID:26457759

  9. 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

  10. Colorectal Cancer in Inflammatory Bowel Disease

    PubMed Central

    Potack, Jonathan

    2008-01-01

    Patients with long-standing inflammatory bowel disease have an increased risk of developing colorectal cancer (CRC). CRC risk increases with longer duration of colitis, greater anatomic extent of colitis, the presence of primary sclerosing cholangitis, family history of CRC and severity of inflammation of the colon. Chemoprevention includes aminosalicylates, ursodeoxycholic acid, and possibly folic acid. To reduce CRC mortality in IBD, colonoscopic surveillance remains the major way to detect early mucosal dysplasia. When dysplasia is confirmed, proctocolectomy is considered for these patients. Ulcerative colitis patients with total proctocolectomy and ileal pouch anal-anastomosis have a rather low risk of dysplasia in the ileal pouch, but the anal transition zone should be monitored periodically. New endoscopic and molecular screening approaches may further refine our current surveillance guidelines and our understanding of the natural history of dysplasia. PMID:20485613

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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. PMID:27148488

  16. 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

  17. 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 ...

  18. [Long-Term Multidisciplinary Therapy for Multiple Liver Metastases from Colorectal Cancer with Biliary Drainage for Occlusive Jaundice--A Case Report].

    PubMed

    Okamura, Shu; Mikami, Koji; Murata, Kohei; Nushijima, Yoichirou; Okada, Kazuyuki; Yanagisawa, Tetsu; Fukuchi, Nariaki; Ebisui, Chikara; Yokouchi, Hideoki; Kinuta, Masakatsu

    2015-11-01

    Here, we report the case of a 43-year-old man who was diagnosed with sigmoid colon cancer with synchronous multiple liver metastases following resection of a primary lesion. Subsequent mFOLFOX+BV therapy elicited a marked response in the liver metastases, which led to the patient undergoing hepatic (S7) radiofrequency ablation (RFA), hepatic resection (lateral segmentectomy and partial [S5] resection), and cholecystectomy. Six months later, transluminal RFA was repeated because liver (S7) metastasis recurred, and 8 courses of XELOX plus BV therapy were administered. As obstructive jaundice due to recurrence of the liver metastases developed after a 6 months hiatus in chemotherapy, we endoscopically inserted a biliary stent. Despite reducing IRIS plus BV therapy, obstructive jaundice developed again, and 3 intrahepatic biliary stents were inserted with percutaneous transhepatic biliary drainage. To date, the patient has been alive for 4 years since the initial resection of the primary lesion after undergoing consecutive systemic chemotherapy with different regimens. Some studies have shown that in cases of obstructive jaundice caused by advanced gastrointestinal cancer, longer survival could be expected by reducing the severity of jaundice, suggesting that resuming chemotherapy as well as improving the severity of jaundice could contribute to better outcomes. The patient in the present case was successfully treated twice with biliary drainage for occlusive jaundice and chemotherapy, suggesting that a combination of multidisciplinary therapy and adequate local therapy such as biliary drainage could be important for the treatment of metastatic liver cancer. PMID:26805157

  19. 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

  20. 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

  1. 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

  2. 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. PMID:26165840

  3. Characterisation of Familial Colorectal Cancer Type X, Lynch syndrome, and non-familial colorectal cancer

    PubMed Central

    Shiovitz, S; Copeland, W K; Passarelli, M N; Burnett-Hartman, A N; Grady, W M; Potter, J D; Gallinger, S; Buchanan, D D; Rosty, C; Win, A K; Jenkins, M; Thibodeau, S N; Haile, R; Baron, J A; Marchand, L L; Newcomb, P A; Lindor, N M

    2014-01-01

    Background: Familial Colorectal Cancer Type X (FCCTX) is defined as individuals with colorectal cancer (CRC) who families meet Amsterdam Criteria-1 (AC1), but whose tumours are DNA-mismatch-repair-proficient, unlike Lynch syndrome (LS). FCCTX does not have an increased risk of extra-colonic cancers. This analysis compares epidemiologic and clinicopathologic features among FCCTX, LS, and ‘non-familial' (non-AC1) CRC cases. Methods: From the Colon Cancer Family Registry, FCCTX (n=173), LS (n=303), and non-AC1 (n=9603) CRC cases were identified. Questionnaire-based epidemiologic information and CRC pathologic features were compared across case groups using polytomous logistic regression. Results: Compared with LS, FCCTX cases were less likely to be current (vs never) smokers; have a proximal subsite (vs rectal) tumour; or have mucinous histology, poor differentiation, or tumour-infiltrating lymphocytes. There were no observed differences in co-morbidities or medication usage. Conclusions: FCCTX were less likely to be current tobacco users; other exposures were similar between these groups. Histopathologic differences highly suggestive of LS CRCs do not appear to be shared by FCCTX. PMID:24918813

  4. Vegetarian Dietary Patterns and the Risk of Colorectal Cancers

    PubMed Central

    Orlich, Michael J.; Singh, Pramil N.; Sabaté, Joan; Fan, Jing; Sveen, Lars; Bennett, Hannelore; Knutsen, Synnove F.; Beeson, W. Lawrence; Jaceldo-Siegl, Karen; Butler, Terry L.; Herring, R. Patti; Fraser, Gary E.

    2015-01-01

    IMPORTANCE Colorectal cancers are a leading cause of cancer mortality, and their primary prevention by diet is highly desirable. The relationship of vegetarian dietary patterns to colorectal cancer risk is not well established. OBJECTIVE To evaluate the association between vegetarian dietary patterns and incident colorectal cancers. DESIGN, SETTING, AND PARTICIPANTS The Adventist Health Study 2 (AHS-2) is a large, prospective, North American cohort trial including 96 354 Seventh-Day Adventist men and women recruited between January 1, 2002, and December 31, 2007. Follow-up varied by state and was indicated by the cancer registry linkage dates. Of these participants, an analytic sample of 77 659 remained after exclusions. Analysis was conducted using Cox proportional hazards regression, controlling for important demographic and lifestyle confounders. The analysis was conducted between June 1, 2014, and October 20, 2014. EXPOSURES Diet was assessed at baseline by a validated quantitative food frequency questionnaire and categorized into 4 vegetarian dietary patterns (vegan, lacto-ovo vegetarian, pescovegetarian, and semivegetarian) and a nonvegetarian dietary pattern. MAIN OUTCOMES AND MEASURES The relationship between dietary patterns and incident cancers of the colon and rectum; colorectal cancer cases were identified primarily by state cancer registry linkages. RESULTS During a mean follow-up of 7.3 years, 380 cases of colon cancer and 110 cases of rectal cancer were documented. The adjusted hazard ratios (HRs) in all vegetarians combined vs nonvegetarians were 0.78 (95% CI, 0.64–0.95) for all colorectal cancers, 0.81 (95%CI, 0.65–1.00) for colon cancer, and 0.71 (95% CI, 0.47–1.06) for rectal cancer. The adjusted HR for colorectal cancer in vegans was 0.84 (95% CI, 0.59–1.19); in lacto-ovo vegetarians, 0.82 (95% CI, 0.65–1.02); in pescovegetarians, 0.57 (95% CI, 0.40–0.82); and in semivegetarians, 0.92 (95% CI, 0.62–1.37) compared with

  5. CCX-CKR expression in colorectal cancer and patient survival.

    PubMed

    Zhu, Yunxiang; Tang, Wentao; Liu, Yun; Wang, Guanghui; Liang, Zhonglin; Cui, Long

    2014-01-01

    Colorectal cancer is one of the most common malignant cancers, with bad prognosis when distal metastasis occurs. The current study aimed to investigate the potential value of using CCX-CKR expression for the prognosis of colorectal cancer patients. The results showed that CCX-CKR expression was a negative predictor of cancer metastasis, and that it was positively correlated to the patients’ survival rate. Finally, we found that CCX-CKR expression in vitro could modulate cellular migration and invasion abilities, potentially via the regulation of other chemotactic factors/receptors. PMID:24338720

  6. 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

  7. 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

  8. 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

  9. Biomarkers in precision therapy in colorectal cancer

    PubMed Central

    Reimers, Marlies S.; Zeestraten, Eliane C.M.; Kuppen, Peter J.K.; Liefers, Gerrit Jan; van de Velde, Cornelis J.H.

    2013-01-01

    Colorectal cancer (CRC) is the most commonly diagnosed cancer in Europe. Because CRC is also a major cause of cancer-related deaths worldwide, a lot of research has been focused on the discovery and development of biomarkers to improve the diagnostic process and to predict treatment outcomes. Up till now only a few biomarkers are recommended by expert panels. Current TNM criteria, however, cause substantial under- and overtreatment of CRC patients. Consequently, there is a growing need for new and efficient biomarkers to ensure optimal treatment allocation. An ideal biomarker should be easily translated into clinical practice, to identify patients who can be spared from treatment or benefit from therapy, ultimately resulting in precision medicine in the future. In this review we aim to provide an overview of a number of frequently studied biomarkers in CRC and, at the same time, we will emphasize the challenges and controversies that withhold the clinical introduction of these biomarkers. We will discuss both prognostic and predictive markers of chemotherapy, aspirin therapy as well as overall therapy toxicity. Currently, only mutant KRAS, mutant BRAF, MSI and the Oncotype DX® Colon Cancer Assay are used in clinical practice. Other biomarker studies showed insufficient evidence to be introduced into clinical practice. Divergent patient selection criteria, absence of validation studies and a large number of single biomarker studies are possibly responsible. We therefore recommend that future studies focus on combining key markers, rather than analysing single markers, standardizing study protocols, and validate the results in independent study cohorts, followed by prospective clinical trials. PMID:24759962

  10. [Clinical study of Peptide-cocktail vaccination with tegafur-uracil/leucovorin for advanced colorectal cancer].

    PubMed

    Sugiura, Fumiaki; Inoue, Keisuke; Okuno, Kiyotaka; Sukegawa, Yasushi

    2012-11-01

    cDNA microarray technology coupled with laser microdissection has been used to identify human leukocyte antigen(HLA)-A24-restricted epitope peptides as potential targets for cancer vaccination in colorectal cancer patients. These antigenic peptides were derived from 2 different testis cancer antigens, ring finger protein 43(RNF43) and translocase of outer mitochondrial membrane 34(TOMM34). We conducted a clinical trial of vaccines against colorectal cancer specific peptides(RNF43 and TOMM34) with tegafur-uracil/Leucovorin( UFT/LV) for the treatment of advanced or recurrent colorectal cancer. The vaccinations were well tolerated without any adverse events. The highest long-term survival was observed in the group showing cytolytic T-lymphocyte (CTL) responses against both RNF43 and TOMM34, followed by the group showing CTL responses against only RNF43 or only TOMM34. A new study has been planned in order to obtain more immunological responses, and we have started a clinical trial of vaccines against multiple peptides[RNF43, TOMM34, forkhead box protein M1(FOXM1), maternal embryonic leucine zipper kinase(MELK), holliday junction recognition protein(HJURP), vascular endothelial growth factor receptor (VEGFR)1, and VEGFR2]by using UFT/LV for the treatment of advanced or recurrent colorectal cancer. PMID:23267878

  11. Molecular pathogenesis of sporadic colorectal cancers.

    PubMed

    Yamagishi, Hidetsugu; Kuroda, Hajime; Imai, Yasuo; Hiraishi, Hideyuki

    2016-01-01

    Colorectal cancer (CRC) results from the progressive accumulation of genetic and epigenetic alterations that lead to the transformation of normal colonic mucosa to adenocarcinoma. Approximately 75% of CRCs are sporadic and occur in people without genetic predisposition or family history of CRC. During the past two decades, sporadic CRCs were classified into three major groups according to frequently altered/mutated genes. These genes have been identified by linkage analyses of cancer-prone families and by individual mutation analyses of candidate genes selected on the basis of functional data. In the first half of this review, we describe the genetic pathways of sporadic CRCs and their clinicopathologic features. Recently, large-scale genome analyses have detected many infrequently mutated genes as well as a small number of frequently mutated genes. These infrequently mutated genes are likely described in a limited number of pathways. Gene-oriented models of CRC progression are being replaced by pathway-oriented models. In the second half of this review, we summarize the present knowledge of this research field and discuss its prospects. PMID:26738600

  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. 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

  14. Genomic landscape of metastatic colorectal cancer

    PubMed Central

    Haan, Josien C.; Labots, Mariette; Rausch, Christian; Koopman, Miriam; Tol, Jolien; Mekenkamp, Leonie J. M.; van de Wiel, Mark A.; Israeli, Danielle; van Essen, Hendrik F.; van Grieken, Nicole C. T.; Voorham, Quirinus J. M.; Bosch, Linda J. W.; Qu, Xueping; Kabbarah, Omar; Verheul, Henk M. W.; Nagtegaal, Iris D.; Punt, Cornelis J. A.; Ylstra, Bauke; Meijer, Gerrit A.

    2014-01-01

    Response to drug therapy in individual colorectal cancer (CRC) patients is associated with tumour biology. Here we describe the genomic landscape of tumour samples of a homogeneous well-annotated series of patients with metastatic CRC (mCRC) of two phase III clinical trials, CAIRO and CAIRO2. DNA copy number aberrations of 349 patients are determined. Within three treatment arms, 194 chromosomal subregions are associated with progression-free survival (PFS; uncorrected single-test P-values <0.005). These subregions are filtered for effect on messenger RNA expression, using an independent data set from The Cancer Genome Atlas which returned 171 genes. Three chromosomal regions are associated with a significant difference in PFS between treatment arms with or without irinotecan. One of these regions, 6q16.1–q21, correlates in vitro with sensitivity to SN-38, the active metabolite of irinotecan. This genomic landscape of mCRC reveals a number of DNA copy number aberrations associated with response to drug therapy. PMID:25394515

  15. Genomic landscape of metastatic colorectal cancer.

    PubMed

    Haan, Josien C; Labots, Mariette; Rausch, Christian; Koopman, Miriam; Tol, Jolien; Mekenkamp, Leonie J M; van de Wiel, Mark A; Israeli, Danielle; van Essen, Hendrik F; van Grieken, Nicole C T; Voorham, Quirinus J M; Bosch, Linda J W; Qu, Xueping; Kabbarah, Omar; Verheul, Henk M W; Nagtegaal, Iris D; Punt, Cornelis J A; Ylstra, Bauke; Meijer, Gerrit A

    2014-01-01

    Response to drug therapy in individual colorectal cancer (CRC) patients is associated with tumour biology. Here we describe the genomic landscape of tumour samples of a homogeneous well-annotated series of patients with metastatic CRC (mCRC) of two phase III clinical trials, CAIRO and CAIRO2. DNA copy number aberrations of 349 patients are determined. Within three treatment arms, 194 chromosomal subregions are associated with progression-free survival (PFS; uncorrected single-test P-values <0.005). These subregions are filtered for effect on messenger RNA expression, using an independent data set from The Cancer Genome Atlas which returned 171 genes. Three chromosomal regions are associated with a significant difference in PFS between treatment arms with or without irinotecan. One of these regions, 6q16.1-q21, correlates in vitro with sensitivity to SN-38, the active metabolite of irinotecan. This genomic landscape of mCRC reveals a number of DNA copy number aberrations associated with response to drug therapy. PMID:25394515

  16. 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

  17. Molecular Markers Predictive of Chemotherapy Response in Colorectal Cancer

    PubMed Central

    Shiovitz, Stacey; Grady, William M.

    2015-01-01

    Recognition of the molecular heterogeneity of colorectal cancer (CRC) has led to the classification of CRC based on a variety of clinical and molecular characteristics. Although the clinical significance of the majority of these molecular alterations is still being ascertained, it is widely anticipated that these characteristics will improve the accuracy of our ability to determine the prognosis and therapeutic response of CRC patients. A few of these markers, such as microsatellite instability and the CpG island methylator phenotype (CIMP), show promise as predictive markers for cytotoxic chemotherapy. KRAS is a validated biomarker for EGFR-targeted therapy, while NRAS and PI3KCA are evolving markers for targeted therapies. Multiple new actionable drug targets are being identified on a regular basis, but most are not ready for clinical use at this time. This review focuses on key molecular features of CRCs and the application of these molecular alterations as predictive biomarkers for CRC. PMID:25663616

  18. 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

  19. Surgeons’ Volume of Colorectal Cancer Procedures and Collaborative Decision-making about Adjuvant Therapies

    PubMed Central

    Rogers, Selwyn O.; Ayanian, John Z.; Ko, Clifford Y.; Kahn, Katherine L.; Zaslavsky, Alan M.; Sandler, Robert S.; Keating, Nancy L.

    2011-01-01

    Background Few studies have assessed associations of surgeons’ practice volume with processes of care that lead to better outcomes. Objective We surveyed surgeons treating colorectal cancer to determine whether high-volume surgeons were more likely to collaborate with other physicians in decisions about adjuvant therapies. Subjects and methods Surgeons caring for patients with colorectal cancer in multiple regions and health-care organizations were surveyed to assess their volume of colorectal cancer resections and participation in decisions about adjuvant chemotherapy and radiation therapy. We used logistic regression to assess physician and practice characteristics associated with surgical volume and the relation of surgical volume and these other characteristics to collaborative decision-making regarding adjuvant therapies. Results Of 635 responding surgeons, those who identified themselves as surgical oncologists or colorectal surgeons were more likely than others to report high volume of colorectal cancer resections (p<.001), as were those who practiced at a comprehensive cancer center (P=.06) and attended tumor board meetings weekly (vs. quarterly or less, P=.09). Most surgeons reported a collaborative role in decisions about chemotherapy and radiation therapy. However, in adjusted analyses, higher-volume surgeons more often reported a collaborative role with other physicians in decisions about chemotherapy (P<0.001) and radiation therapy (P<0.001). Conclusions Higher-volume surgeons are more likely to report collaborating with other physicians in decisions about adjuvant therapies for patients following colorectal cancer surgery. This collaborative decision-making of higher-volume surgeons may contribute to outcome differences by surgeon volume. PMID:19855265

  20. Macroscopic serosal classification of colorectal cancer and its clinical significance

    PubMed Central

    Wang, Yong-Peng; Guo, Peng-Tao; Zhu, Zhi; Zhang, Hao; Xu, Yan; Ma, Si-Ping; Wang, Zhen-Ning; Xu, Hui-Mian

    2015-01-01

    Background: Macroscopic serosal classification of gastric cancer has been reported in previous studies, but rarely reported about it of colorectal cancer. The purpose of this study was to propose a macroscopic serosal classification of colorectal cancer and to investigate clinical significance of this classification. Materials and methods: Morphologic features of colorectal cancer were analyzed according to the macroscopic serosal appearance and clinicopathologic characteristics of these patients were retrospectively reviewed. Microscopic serosal structure was compared between different types under light microscope and transmission electron microscope. Results: Macroscopic serosal classification was divided into normal type, reactive type, nodular type and colloid type according to the macroscopic serosal appearance and microscopic structure. There were significant differences in tumor size, tumor gross type, histological type, histological grade, tumor necrosis, pT stage, number of nodes metastasis, lymph node metastasis ratio, pN stage, M stage and peritoneal metastasis between patients with different serosal types. Univariate analysis of prognosis revealed macroscopic serosal classification as one of factors significantly correlated with patient survival. However, multivariate analysis only revealed TNM stage significantly correlated with patient survival, while macroscopic serosal classification did not, maybe due to insufficient samples. Conclusions: Macroscopic serosal classification of colorectal cancer is preliminarily defined and divided into four types. Different macroscopic serosal types indicate different clinicopathologic features and correlate with prognosis of patients with colorectal cancer, but still cannot be proven as an independent factor. PMID:26884925

  1. 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

  2. Erastin Disrupts Mitochondrial Permeability Transition Pore (mPTP) and Induces Apoptotic Death of Colorectal Cancer Cells

    PubMed Central

    Huo, Haizhong; Zhou, Zhiyuan; Qin, Jian; Liu, Wenyong; Wang, Bing; Gu, Yan

    2016-01-01

    We here evaluated the potential anti-colorectal cancer activity by erastin, a voltage-dependent anion channel (VDAC)-binding compound. Our in vitro studies showed that erastin exerted potent cytotoxic effects against multiple human colorectal cancer cell lines, possibly via inducing oxidative stress and caspase-9 dependent cell apoptosis. Further, mitochondrial permeability transition pore (mPTP) opening was observed in erastin-treated cancer cells, which was evidenced by VDAC-1 and cyclophilin-D (Cyp-D) association, mitochondrial depolarization, and cytochrome C release. Caspase inhibitors, the ROS scavenger MnTBAP, and mPTP blockers (sanglifehrin A, cyclosporin A and bongkrekic acid), as well as shRNA-mediated knockdown of VDAC-1, all significantly attenuated erastin-induced cytotoxicity and apoptosis in colorectal cancer cells. On the other hand, over-expression of VDAC-1 augmented erastin-induced ROS production, mPTP opening, and colorectal cancer cell apoptosis. In vivo studies showed that intraperitoneal injection of erastin at well-tolerated doses dramatically inhibited HT-29 xenograft growth in severe combined immunodeficient (SCID) mice. Together, these results demonstrate that erastin is cytotoxic and pro-apoptotic to colorectal cancer cells. Erastin may be further investigated as a novel anti-colorectal cancer agent. PMID:27171435

  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. Interval cancers in a national colorectal cancer screening programme

    PubMed Central

    Stanners, Greig; Lang, Jaroslaw; Brewster, David H; Carey, Francis A; Fraser, Callum G

    2016-01-01

    Background Little is known about interval cancers (ICs) in colorectal cancer (CRC) screening. Objective The purpose of this study was to identify IC characteristics and compare these with screen-detected cancers (SCs) and cancers in non-participants (NPCs) over the same time period. Design This was an observational study done in the first round of the Scottish Bowel Screening Programme. All individuals (772,790), aged 50–74 years, invited to participate between 1 January 2007 and 31 May 2009 were studied by linking their screening records with confirmed CRC records in the Scottish Cancer Registry (SCR). Characteristics of SC, IC and NPC were determined. Results There were 555 SCs, 502 ICs and 922 NPCs. SCs were at an earlier stage than ICs and NPCs (33.9% Dukes’ A as against 18.7% in IC and 11.3% in NPC), screening preferentially detected cancers in males (64.7% as against 52.8% in IC and 59.7% in NPC): this was independent of a different cancer site distribution in males and females. SC in the colon were less advanced than IC, but not in the rectum. Conclusion ICs account for 47.5% of the CRCs in the screened population, indicating approximately 50% screening test sensitivity: guaiac faecal occult blood testing (gFOBT) sensitivity is less for women than for men and gFOBT screening may not be effective for rectal cancer.

  5. 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.

  6. 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

  7. 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

  8. Angiogenesis Factors Involved in the Pathogenesis of Colorectal Cancer

    PubMed Central

    MIHALACHE, A.; ROGOVEANU, I.

    2014-01-01

    Colorectal cancer stands at the top of oncologic pathology in the world, and in the same measure in Romania because is the third most frequent cancer diagnosed in men and women. Colorectal cancer develops as a result of mutations in genes that control proliferation and cell death. It was established that in the development of a tumor there is originally a prevascular phase followed by a phase of tumor angiogenesis. In the future it is necessary to develop new clinical protocols that angiogenesis inhibitors are associated with chemo or radiotherapy, conventional or other methods such as immunotherapy and gene therapy. PMID:24791198

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. Patients' Experiences With Care for Lung Cancer and Colorectal Cancer: Findings From the Cancer Care Outcomes Research and Surveillance Consortium

    PubMed Central

    Ayanian, John Z.; Zaslavsky, Alan M.; Arora, Neeraj K.; Kahn, Katherine L.; Malin, Jennifer L.; Ganz, Patricia A.; van Ryn, Michelle; Hornbrook, Mark C.; Kiefe, Catarina I.; He, Yulei; Urmie, Julie M.; Weeks, Jane C.; Harrington, David P.

    2010-01-01

    Purpose To assess patients' experiences with cancer care, ratings of their quality of care, and correlates of these assessments. Patients and Methods For 4,093 patients with lung cancer and 3,685 patients with colorectal cancer in multiple US regions and health care delivery systems, we conducted telephone surveys of patients or their surrogates in English, Spanish, or Chinese at 4 to 7 months after diagnosis. The surveys assessed ratings of the overall quality of cancer care and experiences with three domains of interpersonal care (physician communication, nursing care, and coordination and responsiveness of care). Results English-speaking Asian/Pacific Islander patients and Chinese-speaking patients and those in worse health reported significantly worse adjusted experiences with all three domains of interpersonal care, whereas white, black, and Hispanic patients reported generally similar experiences with interpersonal care. The overall quality of cancer care was rated as excellent by 44.4% of patients with lung cancer and 53.0% of patients with colorectal cancer, and these ratings were most strongly correlated with positive experiences with coordination and responsiveness of care (Spearman rank coefficients of 0.49 and 0.42 for lung and colorectal cancer, respectively). After multivariate adjustment, excellent ratings were less common for each cancer among black patients, English-speaking Asian/Pacific Islander patients, Chinese-speaking patients, and patients reporting worse health status (all P ≤ .05). Conclusion Patients' reports and ratings of care differed significantly by race, language, and health status. Efforts to improve patients' experiences with cancer care should focus on problems affecting Asian and Pacific Islander patients and those in worse health. PMID:20713876

  15. No socioeconomic inequalities in colorectal cancer survival within a randomised clinical trial.

    PubMed

    Nur, U; Rachet, B; Parmar, M K B; Sydes, M R; Cooper, N; Lepage, C; Northover, J M A; James, R; Coleman, M P

    2008-12-01

    There is strong evidence that colorectal cancer survival differs between socioeconomic groups. We analysed data on 2481 patients diagnosed during 1989-1997 and recruited to a randomised controlled clinical trial (AXIS, ISRCTN32414363) of chemotherapy and radiotherapy for colorectal cancer. Crude and relative survival at 1 and 5 years was estimated in five categories of socioeconomic deprivation. Multiple imputation was used to account for missing data on tumour stage. A multivariable fractional polynomial model was fitted to estimate the excess hazard of death in each deprivation category, adjusting for the confounding effects of age, stage, cancer site (colon, rectum) and sex, using generalised linear models. Relative survival in the trial patients was higher than in the general population of England and Wales. The socioeconomic gradient in survival was much smaller than that seen for colorectal cancer patients in the general population, both at 1 year -3.2% (95% CI -7.3 to 1.0%, P=0.14) and at 5 years -1.7% (95% CI -8.3 to 4.9%, P=0.61). Given equal treatment, colorectal cancer survival in England and Wales does not appear to depend on socioeconomic status, suggesting that the socioeconomic gradient in survival in the general population could well be due to health-care system factors. PMID:19034284

  16. 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

  17. 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

  18. 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...

  19. PIK3CA in Colorectal Cancer

    PubMed Central

    Cathomas, Gieri

    2014-01-01

    PIK3CA, the catalytic subunit of PI3K, is mutated in many different tumors, including colorectal cancer (CRC). Mutations of PIK3CA have been reported in 10–20% of CRC, about 80% of mutations found in two hot spots in exon 9 and exon 20. In RAS wild-type CRC, PIK3CA mutations have been associated with a worse clinical outcome and with a negative prediction of a response to targeted therapy by anti-EGFR monoclonal antibodies. However, these findings have not been confirmed in all studies and subsequent more detailed analysis has revealed that these effects may be restricted to mutations in Exon 20. Finally, mutations in PIK3CA may be the long sought biomarker for successful adjuvant therapy with aspirin in patients with CRC. Therefore, PIK3CA mutations appear to be a promising predictive biomarker; however, further data are needed to conclusively define the impact of somatic mutations in the PIK3CA gene for the management of patients with CRC. PMID:24624362

  20. Cell Surface Markers in Colorectal Cancer Prognosis

    PubMed Central

    Belov, Larissa; Zhou, Jerry; Christopherson, Richard I.

    2011-01-01

    The classification of colorectal cancers (CRC) is currently based largely on histologically determined tumour characteristics, such as differentiation status and tumour stage, i.e., depth of tumour invasion, involvement of regional lymph nodes and the occurrence of metastatic spread to other organs. These are the conventional prognostic factors for patient survival and often determine the requirement for adjuvant therapy after surgical resection of the primary tumour. However, patients with the same CRC stage can have very different disease-related outcomes. For some, surgical removal of early-stage tumours leads to full recovery, while for others, disease recurrence and metastasis may occur regardless of adjuvant therapy. It is therefore important to understand the molecular processes that lead to disease progression and metastasis and to find more reliable prognostic markers and novel targets for therapy. This review focuses on cell surface proteins that correlate with tumour progression, metastasis and patient outcome, and discusses some of the challenges in finding prognostic protein markers in CRC. PMID:21339979

  1. 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

  2. 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

  3. 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

  4. 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

  5. Risk factors for metachronous colorectal cancer following a primary colorectal cancer: A prospective cohort study.

    PubMed

    Jayasekara, Harindra; Reece, Jeanette C; Buchanan, Daniel D; Rosty, Christophe; Dashti, S Ghazaleh; Ait Ouakrim, Driss; Winship, Ingrid M; Macrae, Finlay A; Boussioutas, Alex; Giles, Graham G; Ahnen, Dennis J; Lowery, Jan; Casey, Graham; Haile, Robert W; Gallinger, Steven; Le Marchand, Loic; Newcomb, Polly A; Lindor, Noralane M; Hopper, John L; Parry, Susan; Jenkins, Mark A; Win, Aung Ko

    2016-09-01

    Individuals diagnosed with colorectal cancer (CRC) are at risk of developing a metachronous CRC. We examined the associations between personal, tumour-related and lifestyle risk factors, and risk of metachronous CRC. A total of 7,863 participants with incident colon or rectal cancer who were recruited in the USA, Canada and Australia to the Colon Cancer Family Registry during 1997-2012, except those identified as high-risk, for example, Lynch syndrome, were followed up approximately every 5 years. We estimated the risk of metachronous CRC, defined as the first new primary CRC following an interval of at least one year after the initial CRC diagnosis. Observation time started at the age at diagnosis of the initial CRC and ended at the age at diagnosis of the metachronous CRC, last contact or death whichever occurred earliest, or were censored at the age at diagnosis of any metachronous colorectal adenoma. Cox regression was used to derive hazard ratios (HRs) and 95% confidence intervals (CIs). During a mean follow-up of 6.6 years, 142 (1.81%) metachronous CRCs were diagnosed (mean age at diagnosis 59.8; incidence 2.7/1,000 person-years). An increased risk of metachronous CRC was associated with the presence of a synchronous CRC (HR = 2.73; 95% CI: 1.30-5.72) and the location of cancer in the proximal colon at initial diagnosis (compared with distal colon or rectum, HR = 4.16; 95% CI: 2.80-6.18). The presence of a synchronous CRC and the location of the initial CRC might be useful for deciding the intensity of surveillance colonoscopy for individuals diagnosed with CRC. PMID:27098183

  6. 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

  7. Neuroendocrine differentiation: The mysterious fellow of colorectal cancer

    PubMed Central

    Kleist, Britta; Poetsch, Micaela

    2015-01-01

    Neuroendocrine differentiation in sporadic colorectal cancer has been recognized since decades, but its clinical impact is still controversially discussed. Detailed parameter analyses hint at the possibility that probably not neuroendocrine differentiation itself, but its association with poor grade of tumor differentiation, lymph node metastases, distant metastases and other unfavorable features contribute to worse clinical outcome. However, other studies deny a relationship between neuroendocrine differentiation and prognosis of colorectal cancer. This review elucidates, whether new insights into the origin of neuroendocrine differentiation in the intestinal epithelium, its regulation by mTOR pathway components and its possible link to the intestinal stem cell compartment could determine a role of neuroendocrine cells as prognostic marker and putative therapeutic target in sporadic colorectal cancer. PMID:26556999

  8. 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

  9. Surgical treatment of hepatic metastases from colorectal cancer

    PubMed Central

    Tsoulfas, Georgios; Pramateftakis, Manousos Georgios; Kanellos, Ioannis

    2011-01-01

    Colorectal carcinoma is one of the most frequent cancers in Western societies with an incidence of around 700 per million people. About half of the patients develop metastases from the primary tumor and liver is the primary metastatic site. Improved survival rates after hepatectomy for metastatic colorectal cancer have been reported in the last few years and these may be the result of a variety of factors, such as advances in systemic chemotherapy, radiographic imaging techniques that permit more accurate determination of the extent and location of the metastatic burden, local ablation methods, and in surgical techniques of hepatic resection. These have led to a more aggressive approach towards liver metastatic disease, resulting in longer survival. The goal of this paper is to review the role of various forms of surgery in the treatment of hepatic metastases from colorectal cancer. PMID:21267397

  10. 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

  11. Role of self expandable stents in management of colorectal cancers

    PubMed Central

    Cetinkaya, Erdinc; Dogrul, Ahmet Bulent; Tirnaksiz, Mehmet Bulent

    2016-01-01

    Acute malignant colorectal obstruction is a complication of colorectal cancer that can occur in 7%-29% of patients. Self-expanding metallic stent placement for malignant colorectal obstruction has gained popularity as a safe and effective procedure for relieving obstruction. This technique can be used in the palliation of malignant colorectal obstruction, as a bridge to elective surgery for resectable colorectal cancers, palliation of extracolonic malignant obstruction, and for nonmalignant etiologies such as anastomotic strictures, Crohn’s disease, radiation therapy, and diverticular diseases. Self-expanding metallic stent has its own advantages and disadvantages over the surgery in these indications. During the insertion of the self-expanding metallic stent, and in the follow-up, short term and long term morbidities should be kept in mind. The most important complications of the stents are perforation, stent obstruction, stent migration, and bleeding. Additionally, given the high risk of perforation, if a patient is treated or being considered fortreatmentwith antiangiogenic agents such as bevacizumab, it is not recommended to use self-expanding metallic stent as a palliative treatment for obstruction. Therefore, there is a need for careful clinical evaluation for each patient who is a candidate for this procedure. The purpose of this review was to evaluate self-expanding metallic stent in the management of the obstruction of the colon due to the colorectal and extracolonic obstruction. PMID:26798442

  12. Effect of Diabetes Mellitus on Outcomes of Colorectal Cancer

    PubMed Central

    Noh, Geum Youb; Hwang, Dae-Yong; Choi, Yoon Hee

    2010-01-01

    Purpose Many studies have revealed that diabetes mellitus (DM) increases a person's lifetime risk of colorectal cancer and that DM is associated with a worse outcome of colon cancer, but this association is controversial. In this study, we intended to examine the relationship between DM and the long-term outcomes of colorectal cancer. Methods A retrospective analysis was conducted on 657 patients who underwent surgery due to colorectal cancer between 1997 and 2004 at Korea Cancer Center Hospital. The operations were done by a single surgeon. With a median follow-up of 4.7 years, we analyzed differences in recurrence-free survival (RFS) and overall survival (OS) between patients with DM and those without DM. Results Of the 657 patients, 374 (57%) were males and 67 (10%) had DM. There was no difference in age at diagnosis, sex and pathologic stage of colorectal cancer according to the presence of DM. There were no difference in the RFS and the OS of colon cancer between the patients with DM and those without DM. At 5 years, the RFS was 71.3% in diabetic patients vs. 70.4% in non-diabetic patients (P = 0.480), and the OS was 68.8% in diabetic patients vs. 75.0% in non-diabetic patients (P = 0.498). There was no difference in the median survival between the groups (9.6 years in the diabetic group vs. 10.6 years in the non-diabetic group; P = 0.495). Conclusion In this study, we did not find any relation between the presence of DM and either the recurrence or the survival in cases of colorectal cancer. More studies to elucidate whether the influence of DM is directly related to a higher rate of cancer recurrence or survival are needed. PMID:21221244

  13. 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

  14. Statin use and the risk of colorectal cancer: A population-based case-control study

    PubMed Central

    Cheng, Meng-Hsuan; Chiu, Hui-Fen; Ho, Shu-Chen; Tsai, Shang-Shyue; Wu, Trong-Neng; Yang, Chun-Yuh

    2011-01-01

    AIM: To investigate whether the use of statins is associated with colorectal cancer risk. METHODS: We conducted a population-based case-control study in Taiwan. Data were retrospectively collected from the Taiwan National Health Insurance Research Database. Cases consisted of all patients who were aged 50 years and older and had a first-time diagnosis of colorectal cancer between the period 2005 and 2008. The controls were matched to cases by age, sex, and index date. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multiple logistic regression. RESULTS: We examined 1156 colorectal cancer cases and 4624 controls. The unadjusted ORs for any statin prescription was 1.10 (95% CI = 0.94-1.30) and the adjusted OR was 1.09 (95% CI = 0.91-1.30). When statin use was categorized by cumulative dose, the adjusted ORs were 0.99 (95% CI = 0.78-1.27) for the group with cumulative statin use below 105 defined daily doses (DDDs); 1.07 (95% CI = 0.78-1.49) for the group with cumulative statin use between 106 and 298.66 DDDs; and 1.30 (95% CI = 0.96-1.75) for the group with cumulative statin use of 298.66 DDDs or more compared with nonusers. CONCLUSION: This study does not provide support for a protective effect of statins against colorectal cancer. PMID:22215945

  15. CD133: A cancer stem cells marker, is used in colorectal cancers

    PubMed Central

    Ren, Fei; Sheng, Wei-Qi; Du, Xiang

    2013-01-01

    Colorectal cancer is one of the most common malignant tumors worldwide. A model of cancer development involving cancer stem cells has been put forward because it provides a possible explanation of tumor hierarchy. Cancer stem cells are characterized by their proliferation, tumorigenesis, differentiation, and self-renewal capacities, and chemoradiotherapy resistance. Due to the role of cancer stem cells in tumor initiation and treatment failure, studies of cancer stem cell markers, such as CD133, have been of great interest. CD133, a five-transmembrane glycoprotein, is widely used as a marker to identify and isolate colorectal cancer stem cells. This marker has been investigated to better understand the characteristics and functions of cancer stem cells. Moreover, it can also be used to predict tumor progression, patient survival, chemoradiotherapy resistance and other clinical parameters. In this review, we discuss the use of CD133 in the identification of colorectal cancer stem cell, which is currently controversial. Although the function of CD133 is as yet unclear, we have discussed several possible functions and associated mechanisms that may partially explain the role of CD133 in colorectal cancers. In addition, we focus on the prognostic value of CD133 in colorectal cancers. Finally, we predict that CD133 may be used as a possible target for colorectal cancer treatment. PMID:23674867

  16. Immunotherapy in colorectal cancer: What have we learned so far?

    PubMed

    Sanchez-Castañón, María; Er, Tze-Kiong; Bujanda, Luis; Herreros-Villanueva, Marta

    2016-09-01

    After decades of progress based on chemotherapy and targeted agents, patients with metastatic colorectal cancer still have low long-term survival, with more than 500,000 deaths occurring worldwide every year. Recent results showing clinical evidence of efficacy using immunotherapy in other types of tumors, such as melanoma and lung cancer, have also made this a viable therapy for evaluation in colorectal cancer in clinical trials. The development of cancer immunotherapies is progressing quickly, with a variety of technological approaches. This review summarizes the current status of clinical trials testing immunotherapy in colorectal cancer and discusses what has been learned based on previous results. Immunotherapy strategies, such as various models of vaccines, effector-cell therapy and checkpoint inhibitor antibodies, provide protection against progression for a limited subset of patients diagnosed with colorectal cancer. A better understanding of particular immune cell types and pathways in each patient is still needed. These findings will enable the development of novel biomarkers to select the appropriate subset of patients to be treated with a particular immunotherapy, and the tendencies determined from recent results can guide clinical practice for oncologists in this new therapeutic area and in the design of the next round of clinical trials. PMID:27350293

  17. Characteristics and prognosis of colorectal cancer associated with rheumatic disease.

    PubMed

    Kishikawa, Junko; Kawai, Kazushige; Tsuno, Nelson H; Ishihara, Soichiro; Yamaguchi, Hironori; Sunami, Eiji; Watanabe, Toshiaki

    2015-05-01

    It is well known that host immunity plays an important role in the defense against colorectal cancer (CRC) progression. The effects of autoimmune diseases, such as rheumatic disease (RD) in which the immune system is deregulated, on this immunity have not been fully investigated. The medical records of 1299 consecutive patients diagnosed with primary colorectal cancer who underwent surgical resection were retrospectively reviewed. The clinicopathologic factors of 28 subjects with RD (RD group) were compared with those of 1271 patients without RD (non-RD group). Compared to the non-RD group, the RD group was typified by a predominance of females (P < 0.01), older age (P < 0.01), and a lower incidence of rectal cancer (P = 0.02). Although no difference was observed between the groups in terms of TNM classification, disease-free and overall survival were significantly poorer in the RD group in both univariate and multivariate analyses. Subjects who had RD for more than 10 years tended to have a higher frequency of lymph node metastasis (P = 0.06) and a significantly higher incidence of synchronous distant metastasis (P = 0.035) at the time of cancer diagnosis. RD was associated with a significantly poorer prognosis of colorectal cancer, suggesting that deregulation of the immune system by autoimmune diseases may adversely affect the host immune defense against colorectal cancer progression. PMID:25556608

  18. Characteristics and Prognosis of Colorectal Cancer Associated With Rheumatic Disease

    PubMed Central

    Kishikawa, Junko; Kawai, Kazushige; Tsuno, Nelson H.; Ishihara, Soichiro; Yamaguchi, Hironori; Sunami, Eiji; Watanabe, Toshiaki

    2015-01-01

    It is well known that host immunity plays an important role in the defense against colorectal cancer (CRC) progression. The effects of autoimmune diseases, such as rheumatic disease (RD) in which the immune system is deregulated, on this immunity have not been fully investigated. The medical records of 1299 consecutive patients diagnosed with primary colorectal cancer who underwent surgical resection were retrospectively reviewed. The clinicopathologic factors of 28 subjects with RD (RD group) were compared with those of 1271 patients without RD (non-RD group). Compared to the non-RD group, the RD group was typified by a predominance of females (P < 0.01), older age (P < 0.01), and a lower incidence of rectal cancer (P = 0.02). Although no difference was observed between the groups in terms of TNM classification, disease-free and overall survival were significantly poorer in the RD group in both univariate and multivariate analyses. Subjects who had RD for more than 10 years tended to have a higher frequency of lymph node metastasis (P = 0.06) and a significantly higher incidence of synchronous distant metastasis (P = 0.035) at the time of cancer diagnosis. RD was associated with a significantly poorer prognosis of colorectal cancer, suggesting that deregulation of the immune system by autoimmune diseases may adversely affect the host immune defense against colorectal cancer progression. PMID:25556608

  19. 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

  20. 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

  1. 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

  2. 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.

  3. [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

  4. Genetic variation in sex-steroid receptors and synthesizing enzymes and colorectal cancer risk in women

    PubMed Central

    Lin, Jennifer; Zee, Robert Y.L.; Liu, Kuang-Yu; Zhang, Shumin M.; Lee, I-Min; Manson, JoAnn E.; Giovannucci, Edward; Buring, Julie E.; Cook, Nancy R.

    2010-01-01

    Objectives Several lines of evidence have suggested that female hormones may lower risk for developing colorectal cancer. However, the mechanisms by which sex hormones affect colorectal cancer development remain unknown. We sought to determine whether the association may be under genetic control by evaluating genetic variation in estrogen receptors (ESR1 and ESR2), progesterone receptor (PGR), aromatase cytochrome 450 enzyme (CYP19A1) and 17 beta-hydroxysteroid dehydrogenase type 2 gene (HSD17B2). Methods We included 158 incident cases of colorectal cancer and 563 randomly chosen control subjects from 28,345 women in the Women's Health Study aged 45 years or older who provided blood samples and had no history of cancer or cardiovascular disease at baseline in 1993. All cases and controls were Caucasians of European descent. A total of 63 tagging and putative functional SNPs in the 5 genes were included for analysis. Unconditional logistic regression was used to estimate odds ratio (ORs) and 95% confidence intervals (CIs). Results There was no association between variation in ESR1, ESR2, PGR, CYP19A1 and HSD17B2 and colorectal cancer risk after correction for multiple comparisons (p values after correction ≥0.25). There was also no association with any of the haplotypes examined (p ≥0.15) and no evidence of joint effects of variants in the 5 genes (p ≥0.51). Conclusion Our data offer insufficient support for an association between variation in ESR1, ESR2, PGR, CYP19A1 and HSD17B2 and risk for developing colorectal cancer. PMID:20148360

  5. 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.

  6. Single-incision laparoscopic surgery for colorectal cancer

    PubMed Central

    Hirano, Yasumitsu; Hattori, Masakazu; Douden, Kenji; Ishiyama, Yasuhiro; Hashizume, Yasuo

    2016-01-01

    AIM: To determine the effect of single-incision laparoscopic colectomy (SILC) for colorectal cancer on short-term clinical and oncological outcomes by comparison with multiport conventional laparoscopic colectomy (CLC). METHODS: A systematic review was performed using MEDLINE for the time period of 2008 to December 2014 to retrieve all relevant literature. The search terms were “laparoscopy”, “single incision”, “single port”, “single site”, “SILS”, “LESS” and “colorectal cancer”. Publications were included if they were randomized controlled trials, case-matched controlled studies, or comparative studies, in which patients underwent single-incision (SILS or LESS) laparoscopic colorectal surgery. Studies were excluded if they were non-comparative, or not including surgery involving the colon or rectum. A total of 15 studies with 589 patients who underwent SILC for colorectal cancer were selected. RESULTS: No significant differences between the groups were noted in terms of mortality or morbidity. The benefit of the SILC approach included reduction in conversion rate to laparotomy, but there were no significant differences in other short-term clinical outcomes between the groups. Satisfactory oncological surgical quality was also demonstrated for SILC for the treatment of colorectal cancer with a similar average lymph node harvest and proximal and distal resection margin length as multiport CLC. CONCLUSION: SILC can be performed safely with similar short-term clinical and oncological outcomes as multiport CLC. PMID:26843918

  7. 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

  8. 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. PMID:26681340

  9. 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. PMID:22187109

  10. A Comprehensive Study of Extramural Venous Invasion in Colorectal Cancer

    PubMed Central

    McClelland, David; Murray, Graeme I

    2015-01-01

    Colorectal cancer is a common malignancy and a leading cause of cancer related death. Cancer staging following resection is key to determining any adjuvant therapy in those patients with high risk disease. In colorectal cancer, tumour stage and lymph node stage are the main pathological factors which have been considered to influence outcome. Increasing emphasis is now being placed on other factors, especially the presence of extramural venous invasion (EMVI). It is important to understand the relationship of EMVI with other pathological factors and to confirm that in an individual centre that EMVI is being detected at an appropriate rate and is of prognostic significance. This comprehensive study assesses the reporting and prognostic significance of EMVI in a single centre, using prospectively collected data from histopathology reports of a cohort of 2405 patients who underwent surgery for colorectal cancer over a nine year period. Overall, EMVI was reported in 27.9% of colorectal cancer excision specimens. In tumours (n = 1928) that had not received neoadjuvant therapy, the presence of EMVI varied significantly depending on tumour site (χ2 = 12.03, p<0.005), tumour stage (χ2 = 268.188, p<0.001), lymph node stage (χ2 = 294.368, p<0.001) and Dukes’ stage (χ2 = 253.753, p<0.001). Multivariate analysis confirmed EMVI as a significant independent prognostic indicator (p<0.001). In conclusion, the presence of EMVI as an independent prognostic indicator is shown and is related to other pathological and prognostic factors. This study emphasises the requirement for the accurate identification of EMVI in colorectal cancer excision specimens and also understanding the relationship of EMVI with other prognostic factors. PMID:26671331

  11. 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

  12. Induction of colorectal cancer in mice and histomorphometric evaluation of tumors.

    PubMed

    Crncec, Ilija; Pathria, Paulina; Svinka, Jasmin; Eferl, Robert

    2015-01-01

    Colorectal cancer (CRC) originates from the epithelial cells lining the colon or rectum of the gastrointestinal tract and represents the third most common form of cancer worldwide. CRC is frequently associated with Colitis Ulcerosa or Crohn's Disease demonstrating the tumor-promoting role of inflammation. Colorectal tumor cells establish heterotypic interactions with inflammatory cells and cancer-associated fibroblasts in the tumor stroma that support tumor angiogenesis and are essential for tumor progression. Therefore, establishment of suitable mouse models mimicking the inflammatory etiology of CRC is important. Here we describe methods to induce CRC in mice, to quantify tumor parameters (multiplicity, tumor load, mean tumor size), and to analyze the cellular composition of the CRC tumor stroma. PMID:25636468

  13. Comparative Proteomic Analysis of Cysteine Oxidation in Colorectal Cancer Patients

    PubMed Central

    Yang, Hee-Young; Chay, Kee-Oh; Kwon, Joseph; Kwon, Sang-Oh; Park, Young-Kyu; Lee, Tae-Hoon

    2013-01-01

    Oxidative stress promotes damage to cellular proteins, lipids, membranes and DNA, and plays a key role in the development of cancer. Reactive oxygen species disrupt redox homeostasis and promote tumor formation by initiating aberrant activation of signaling pathways that lead to tumorigenesis. We used shotgun proteomics to identify proteins containing oxidation-sensitive cysteines in tissue specimens from colorectal cancer patients. We then compared the patterns of cysteine oxidation in the membrane fractions between the tumor and non-tumor tissues. Using nano-UPLC-MSE proteomics, we identified 31 proteins containing 37 oxidation-sensitive cysteines. These proteins were observed with IAM-binding cysteines in non-tumoral region more than tumoral region of CRC patients. Then using the Ingenuity pathway program, we evaluated the cellular canonical networks connecting those proteins. Within the networks, proteins with multiple connections were related with organ morphology, cellular metabolism, and various disorders. We have thus identified networks of proteins whose redox status is altered by oxidative stress, perhaps leading to changes in cellular functionality that promotes tumorigenesis. PMID:23677378

  14. 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

  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. Role of colonic stents in the management of colorectal cancers

    PubMed Central

    Sagar, Jayesh

    2016-01-01

    Colorectal cancer is one of the commonly encountered cancers across the Western World. In United Kingdom, this constitutes third most common ranked cancer and second most common ranked cause of cancer related deaths. Its acute presentation as a malignant colonic obstruction imposes challenges in its management. Colonic stent has been used for many years to alleviate acute obstruction in such cases allowing optimisation of patient’s physiological status and adequate staging of cancer. In this review, current literature evidence regarding use of colonic stent in acute malignant colonic obstruction is critically appraised and recommendations on the use of colonic stent are advocated. PMID:26962401

  17. Functional TLR5 genetic variants affect human colorectal cancer survival.

    PubMed

    Klimosch, Sascha N; Försti, Asta; Eckert, Jana; Knezevic, Jelena; Bevier, Melanie; von Schönfels, Witigo; Heits, Nils; Walter, Jessica; Hinz, Sebastian; Lascorz, Jesus; Hampe, Jochen; Hartl, Dominik; Frick, Julia-Stefanie; Hemminki, Kari; Schafmayer, Clemens; Weber, Alexander N R

    2013-12-15

    Toll-like receptors (TLR) are overexpressed on many types of cancer cells, including colorectal cancer cells, but little is known about the functional relevance of these immune regulatory molecules in malignant settings. Here, we report frequent single-nucleotide polymorphisms (SNP) in the flagellin receptor TLR5 and the TLR downstream effector molecules MyD88 and TIRAP that are associated with altered survival in a large cohort of Caucasian patients with colorectal cancer (n = 613). MYD88 rs4988453, a SNP that maps to a promoter region shared with the acetyl coenzyme-A acyl-transferase-1 (ACAA1), was associated with decreased survival of patients with colorectal cancer and altered transcriptional activity of the proximal genes. In the TLR5 gene, rs5744174/F616L was associated with increased survival, whereas rs2072493/N592S was associated with decreased survival. Both rs2072493/N592S and rs5744174/F616L modulated TLR5 signaling in response to flagellin or to different commensal and pathogenic intestinal bacteria. Notably, we observed a reduction in flagellin-induced p38 phosphorylation, CD62L shedding, and elevated expression of interleukin (IL)-6 and IL-1β mRNA in human primary immune cells from TLR5 616LL homozygote carriers, as compared with 616FF carriers. This finding suggested that the well-documented effect of cytokines like IL-6 on colorectal cancer progression might be mediated by TLR5 genotype-dependent flagellin sensing. Our results establish an important link between TLR signaling and human colorectal cancer with relevance for biomarker and therapy development. PMID:24154872

  18. 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

  19. 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

  20. 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

  1. 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

  2. Controversies in the pathological assessment of colorectal cancer

    PubMed Central

    Maguire, Aoife; Sheahan, Kieran

    2014-01-01

    Pathologic assessment of colorectal cancer specimens plays an essential role in patient management, informing prognosis and contributing to therapeutic decision making. The tumor-node-metastasis (TNM) staging system is a key component of the colorectal cancer pathology report and provides important prognostic information. However there is significant variation in outcome of patients within the same tumor stage. Many other histological features such as tumor budding, vascular invasion, perineural invasion, tumor grade and rectal tumor regression grade that may be of prognostic value are not part of TNM staging. Assessment of extramural tumor deposits and peritoneal involvement contributes to TNM staging but there are some difficulties with the definition of both of these features. Controversies in colorectal cancer pathology reporting include the subjective nature of some of the elements assessed, poor reporting rates and reproducibility and the need for standardized examination protocols and reporting. Molecular pathology is becoming increasingly important in prognostication and prediction of response to targeted therapies but accurate morphology still has a key role to play in colorectal cancer pathology reporting. PMID:25110416

  3. Colorectal Cancer: Prevention and Management of Metastatic Disease

    PubMed Central

    Sugarbaker, Paul H.

    2014-01-01

    This paper compared the similarities and differences of the two most common types of colorectal cancer metastases. The treatment of liver metastases by surgery combined with systemic chemotherapy was explained. The different natural history of liver metastases as compared to peritoneal metastases and the possibility for prevention of peritoneal metastases were emphasized. Perioperative cancer chemotherapy or second-look surgery must be considered as individualized treatments of selected patients who have small volume peritoneal metastases or who are known to be at risk for subsequent disease progression on peritoneal surfaces. However, the fact that peritoneal metastases, when diagnosed in the follow-up of colorectal cancer patients, can be cured with a combination of cytoreductive surgery and hyperthermic perioperative chemotherapy cannot be ignored. Careful follow-up and timely intervention in colorectal cancer patients with progressive disease are a necessary part of the management strategies recommended by the multidisciplinary team. After a critical evaluation of the data currently available, these strategies for prevention and management of colorectal metastases are presented as the author's recommendations for a high standard of care. As more information becomes available, modifications may be necessary. PMID:24783222

  4. 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

  5. Sex differences in hospital readmission among colorectal cancer patients

    PubMed Central

    Gonzalez, J. R.; Fernandez, E.; Moreno, V.; Ribes, J.; Peris, M.; Navarro, M.; Cambray, M.; Borras, J. M.

    2005-01-01

    Background: While several studies have analysed sex and socioeconomic differences in cancer incidence and mortality, sex differences in oncological health care have been seldom considered. Objective: To investigate sex based inequalities in hospital readmission among patients diagnosed with colorectal cancer. Design: Prospective cohort study. Setting: Hospital Universitary in L'Hospitalet (Barcelona, Spain). Participants: Four hundred and three patients diagnosed with colorectal between January 1996 and December 1998 were actively followed up until 2002. Main outcome measurements and methods: Hospital readmission times related to colorectal cancer after surgical procedure. Cox proportional model with random effect (frailty) was used to estimate hazard rate ratios and 95% confidence intervals of readmission time for covariates analysed. Results: Crude hazard rate ratio of hospital readmission in men was 1.61 (95% CI 1.21 to 2.15). When other significant determinants of readmission were controlled for (including Dukes's stage, mortality, and Charlson's index) a significant risk of readmission was still present for men (hazard rate ratio: 1.52, 95% CI 1.17 to 1.96). Conclusions: In the case of colorectal cancer, women are less likely than men to be readmitted to the hospital, even after controlling for tumour characteristics, mortality, and comorbidity. New studies should investigate the role of other non-clinical variable such as differences in help seeking behaviours or structural or personal sex bias in the attention given to patients. PMID:15911648

  6. 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…

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

    PubMed

    Herr, Ricarda; Brummer, Tilman

    2015-01-01

    BRAF inhibitor monotherapy appears to be ineffective in BRAF (V600E)-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

  8. 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. PMID:24274588

  9. SPINK1 promotes colorectal cancer progression by downregulating Metallothioneins expression

    PubMed Central

    Tiwari, R; Pandey, S K; Goel, S; Bhatia, V; Shukla, S; Jing, X; Dhanasekaran, S M; Ateeq, B

    2015-01-01

    Colorectal cancer (CRC) is the third most common cancer in the world, and second leading cause of cancer deaths in the US. Although, anti-EGFR therapy is commonly prescribed for CRC, patients harboring mutations in KRAS or BRAF show poor treatment response, indicating an ardent demand for new therapeutic targets discovery. SPINK1 (serine peptidase inhibitor, Kazal type 1) overexpression has been identified in many cancers including the colon, lung, breast and prostate. Our study demonstrates the functional significance of SPINK1 in CRC progression and metastases. Stable knockdown of SPINK1 significantly decreases cell proliferation, invasion and soft agar colony formation in the colon adenocarcinoma WiDr cells. Conversely, an increase in these oncogenic phenotypes was observed on stimulation with SPINK1-enriched conditioned media (CM) in multiple benign models such as murine colonic epithelial cell lines, MSIE and YAMC (SPINK3-negative). Mechanistically, SPINK1 promotes tumorigenic phenotype by activating phosphatidylinositol 3-kinase (PI3K/AKT) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathways, and the SPINK1-positive WiDr cells are sensitive to AKT and MEK inhibitors. Importantly, SPINK1 silencing mediated upregulation of various Metallothionein isoforms, considered as tumor suppressors in CRC, confer sensitivity to doxorubicin, which strengthens the rationale for using the combinatorial treatment approach for the SPINK1-positive CRC patients. Furthermore, in vivo studies using chicken chorioallantoic membrane assay, murine xenograft studies and metastasis models further suggest a pivotal role of SPINK1 in CRC progression and metastasis. Taken together, our study demonstrates an important role for the overexpressed SPINK1 in CRC disease progression, a phenomenon that needs careful evaluation towards effective therapeutic target development. PMID:26258891

  10. 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

  11. The expression and role of CXC chemokines in colorectal cancer.

    PubMed

    Verbeke, Hannelien; Struyf, Sofie; Laureys, Geneviève; Van Damme, Jo

    2011-01-01

    Cancer is a life-threatening disease world-wide and colorectal cancer is the second common cause of cancer mortality. The interaction between tumor cells and stromal cells plays a crucial role in tumor initiation and progression and is partially mediated by chemokines. Chemokines predominantly participate in the chemoattraction of leukocytes to inflammatory sites. Nowadays, it is clear that CXC chemokines and their receptors (CXCR) may also modulate tumor behavior by several important mechanisms: regulation of angiogenesis, activation of a tumor-specific immune response by attracting leukocytes, stimulation of tumor cell proliferation and metastasis. Here, we review the expression and complex roles of CXC chemokines (CXCL1 to CXCL16) and their receptors (CXCR1 to CXCR6) in colorectal cancer. Overall, increased expression levels of CXC chemokines correlate with poor prognosis. PMID:22000992

  12. 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

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

    PubMed

    Vogtmann, Emily; 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

  14. Personality as a risk factor in large bowel cancer: data from the Melbourne Colorectal Cancer Study.

    PubMed

    Kune, G A; Kune, S; Watson, L F; Bahnson, C B

    1991-02-01

    In a case control study which formed one arm of a large, population-based investigation of colorectal cancer incidence, aetiology and survival. 'The Melbourne Colorectal Cancer Study', among others, 22 psychosocially orientated questions were asked by personal interview of 637 histologically confirmed new cases of colorectal cancer and 714 age/sex frequency matched community controls, from Melbourne (population 2.81 million). Self-reported childhood or adult life 'unhappiness' was statistically significantly more common among the cancer cases, while 'unhappiness with retirement' was similarly distributed among cases and controls. Questions which were formulated to test a particular personality profile as a cancer risk, and which included the elements of denial and repression of anger and of other negative emotions, a commitment to prevailing social norms resulting in the external appearance of a 'nice' or 'good' person, a suppression of reactions which may offend others and the avoidance of conflict, showed a statistically significant discrimination between cases and controls. The risk of colorectal cancer with respect to this model was independent of the previously found risk factors of diet, beer intake, and family history of colorectal cancer, and was also independent of other potential confounding factors of socioeconomic level, marital status, religion and country of birth. Although the results must be interpreted with caution, the data are consistent with the hypothesis that this personality type may play a role in the clinical expression of colorectal cancer and merits further study. PMID:2047503

  15. 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

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

    PubMed

    Wheeler, Scott R; Shi, Chanjuan; Holt, Jonathan A; Vnencak-Jones, Cindy L

    2016-06-01

    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

  17. 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

  18. Psychological Barriers and Facilitators of Colorectal Cancer Screening: A French Qualitative Study

    PubMed Central

    Bridou, Morgiane; Aguerre, Colette; Gimenes, Guillaume; Kubiszewski, Violaine; Le Gall, Armel; Potard, Catherine; Sorel, Olivier; Reveillere, Christian

    2013-01-01

    The aim of this qualitative study was to explore the psychological barriers to and facilitators of undergoing the Hemoccult-II® colorectal cancer screening test in France. Sixty-nine French people aged 50 to 74 years were divided into seven qualitative focus groups. Three issues were discussed with participants: knowledge and beliefs about colorectal cancer screening; facilitators of colorectal cancer screening by Hemoccult-II®; barriers to colorectal cancer screening by Hemoccult-II®. All the discussions were led by two psychologists and were recorded, transcribed verbatim and analyzed using qualitative data analysis software. Correspondence factor analyses identified three dimensions for each topic. The main psychological facilitators of colorectal cancer screening were: information about colorectal cancer screening, perceived simplicity of using Hemoccult-II®, and perception of risk. Uncertainty about the reliability of Hemoccult-II®, health anxiety, and embarrassment emerged as the main barriers to colorectal cancer screening. Cross-sectional analyses identified the differences between the views expressed by women and men. Women appeared more embarrassed about Hemoccult-II® and men seemed to be more worried about colorectal cancer. This preliminary study suggests that psychological factors play an important role in colorectal cancer screening by Hemoccult-II®. This finding may help health organizations to conceive better awareness campaigns to promote colorectal cancer screening in order to reduce the related mortality rate by taking into account psychological determinants. PMID:26973907

  19. 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

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

    PubMed

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

    2016-04-01

    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

  1. 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. PMID:26566853

  2. 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

  3. A systematic review of a liver-first approach in patients with colorectal cancer and synchronous colorectal liver metastases

    PubMed Central

    Lam, Vincent WT; Laurence, Jerome M; Pang, Tony; Johnston, Emma; Hollands, Michael J; Pleass, Henry CC; Richardson, Arthur J

    2014-01-01

    Background: Since the liver metastases rather than the colorectal cancer itself is the main determinant of patient’s survival, the ‘Liver-First Approach (LFA)’ with upfront chemotherapy followed by a hepatic resection of colorectal liver metastases (CLM) and finally a colorectal cancer resection was proposed. The aim of this review was to analyse the evidence for LFA in patients with colorectal cancer and synchronous CLM. Methods: A literature search of databases (MEDLINE and EMBASE) to identify published studies of LFA in patients with colorectal cancer and synchronous CLM was undertaken focussing on the peri-operative regimens of LFA and survival outcomes. Results: Three observational studies and one retrospective cohort study were included for review. A total of 121 patients with colorectal cancer and synchronous CLM were selected for LFA. Pre-operative chemotherapy was used in 99% of patients. One hundred and twelve of the initial 121 patients (93%) underwent a hepatic resection of CLM. In total, 60% had a major liver resection and the R0 resection rate was 93%. Post-operative morbidity and mortality after the hepatic resection were 20% and 1%, respectively. Ultimately, 89 of the initial 121 (74%) patients underwent a colorectal cancer resection. Post-operative morbidity and mortality after a colorectal resection were 50% and 6%, respectively. The median overall survival was 40 months (range 19–50) with a recurrence rate of 52%. Conclusions: Current evidence suggests that LFA is safe and feasible in selected patients with colorectal cancer and synchronous CLM. Future studies are required to further define patient selection criteria for LFA and the exact role of LFA in the management of synchronous CLM. PMID:23509899

  4. 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

  5. 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

  6. 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

  7. 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

  8. Cost benefit of early diagnosis of colorectal cancer.

    PubMed

    Bolin, T D

    1996-01-01

    In most Western countries, colorectal cancer is an important disease in terms of morbidity and mortality. As it has a premalignant asymptomatic stage in the form of benign adenomas that might be detected by screening, and as screening leads to detection of colorectal cancer at an earlier stage, there is potential for improved and better quality survival. Most cost-effective analyses rank the various screening strategies at less than an accepted benchmark value of approximately $40,000 per added year of life. Periodic colorectal screening is therefore a cost-effective intervention and the Office of Technology Assessment of the Congress of the United States has concluded that colorectal cancer screening in average-risk adults beginning at age 50 is a relatively good investment for society. Flexible sigmoidoscopy and double contrast barium enema are the most cost-effective strategies but they both require colonoscopy if a lesion is identified. Colonoscopy at 10-yearly intervals is of comparable cost to flexible sigmoidoscopy every 5 years and less costly than FSIG every 3 years. Combination strategies, using faecal occult blood testing with periodic flexible sigmoidoscopy or double contrast barium enema are as costly as colonoscopy. The choice of screening strategies needs to be tailored to the individual, and a process of community education is an essential prerequisite to the success of any programme. PMID:8898453

  9. Role of MGMT as biomarker in colorectal cancer

    PubMed Central

    Inno, Alessandro; Fanetti, Giuseppe; Di Bartolomeo, Maria; Gori, Stefania; Maggi, Claudia; Cirillo, Massimo; Iacovelli, Roberto; Nichetti, Federico; Martinetti, Antonia; de Braud, Filippo; Bossi, Ilaria; Pietrantonio, Filippo

    2014-01-01

    O6-methylguanine DNA methyltransferase (MGMT) gene promoter methylation plays an important role in colorectal carcinogenesis, occurring in about 30%-40% of metastatic colorectal cancer. Its prognostic role has not been defined yet, but loss of expression of MGMT, which is secondary to gene promoter methylation, results in an interesting high response to alkylating agents such as dacarbazine and temozolomide. In a phase 2 study on heavily pre-treated patients with MGMT methylated metastatic colorectal cancer, temozolomide achieved about 30% of disease control rate. Activating mutations of RAS or BRAF genes as well as mismatch repair deficiency may represent mechanisms of resistance to alkylating agents, but a dose-dense schedule of temozolomide may potentially restore sensitivity in RAS-mutant patients. Further development of temozolomide in MGMT methylated colorectal cancer includes investigation of synergic combinations with other agents such as fluoropyrimidines and research for additional biomarkers, in order to better define the role of temozolomide in the treatment of individual patients. PMID:25516857

  10. 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.

  11. 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

  12. Radiofrequency Ablation of Liver Metastases from Colorectal Cancer: A Literature Review

    PubMed Central

    Kudo, Masatoshi

    2013-01-01

    Liver metastases occur in up to 60% of patients with colorectal cancer, and the control of liver metastases is considered to be of primary importance because it is a critical factor in determining prognosis. Radiofrequency ablation (RFA) therapy is one of the least invasive techniques for unresectable hepatic malignancies and can be performed safely using percutaneous, laparoscopic, or open surgical techniques. The local tumor progression rates after RFA for colorectal liver metastases range from 8.8% to 40.0%, and 5-year survival rates range from 20.0% to 48.5%. No prospective, randomized trials comparing the efficacy of RFA with that of surgical resection for colorectal liver metastases are currently available. However, some retrospective studies have reported that patients who received RFA had a survival rate similar to that observed in surgically treated groups, while other studies have reported better survival among patients who underwent surgical resection. The use of a laparoscopic or open surgical approach allows the repeated placement of RFA electrodes at multiple sites to ablate larger tumors. An accurate evaluation of treatment response is very important for the success of RFA therapy because a sufficient safety margin (at least 0.5 cm) can prevent local tumor progression. This review critically summarizes the current status of RFA for liver metastases from colorectal cancer. PMID:23422905

  13. Network-based analysis for identification of candidate genes for colorectal cancer progression.

    PubMed

    Tsuji, Shingo; Midorikawa, Yutaka; Seki, Motoaki; Takayama, Tadatoshi; Sugiyama, Yasuyuki; Aburatani, Hiroyuki

    2016-08-01

    Although high-throughput biological technologies have been producing a vast amount of multi-omics data regarding cancer genomics and several disease susceptible genes have been reported, many of these genes are likely to be irrelevant for the cancer process because only one feature of the tumor pathway could be focused on. By identifying 'CpG core', which was extracted from CpG sites in genomic DNA by our newly developed method, we performed integrated analysis using gene expression and DNA methylation profiles of 116 colorectal cancer samples. First, based on gene expression values, colorectal cancer samples were divided into three clusters (Cluster-1, -2, and -3) by k-means clustering. The 5-year overall survival rates of colorectal cancer patients were 74.8%, 29.2%, and 29.4% in Cluster-1, -2, and -3, respectively, and the prognosis of Cluster-2 was significantly poorer than that of the other two clusters owing to liver metastasis (P < 0.001). Second, each cluster was divided into two subgroups based on methylation status, and the 5-year overall survival rate of Cluster-1H (36.8%) was significantly shorter than that of Cluster-1L (96.1%) due to the accumulation of aberrant DNA methylation (P = 0.014). Third, network-based analysis using expression and methylation profiles demonstrated that nucleoporin family genes were downregulated in Cluster-2 and that the PTX3 gene was highly methylated in Cluster-1H. These combined data indicate that integrated analysis can identify disease characteristics that would be missed using single comprehensive analysis, and that multiple pathways would play pivotal roles in the liver metastasis of colorectal cancer. PMID:27255996

  14. MicroRNAs as non-invasive screening biomarkers of colorectal cancer

    PubMed Central

    SAPLACAN, ROBERTA MARIA MANZAT; MIRCEA, PETRU ADRIAN; BALACESCU, LOREDANA; BALACESCU, OVIDIU

    2015-01-01

    Colorectal cancer is a major cause of cancer-associated deaths in the world. Early detection would be greatly enhanced if accurate and cost-effective diagnostic biomarkers for this disease were accessible. The development of such a blood test will evidently lower the screening costs in regards of colorectal cancer detection. Lately, it has been suggested that microRNA diagnostic biomarkers are feasible new screening methods for colorectal cancer. This review summarizes the diagnostic potential of circulating microRNA biomarkers in relation with colorectal cancer, as well as current methods to detect them. PMID:26733742

  15. 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

  16. 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

  17. Tumor-derived circulating endothelial cell clusters in colorectal cancer.

    PubMed

    Cima, Igor; Kong, Say Li; Sengupta, Debarka; Tan, Iain B; Phyo, Wai Min; Lee, Daniel; Hu, Min; Iliescu, Ciprian; Alexander, Irina; Goh, Wei Lin; Rahmani, Mehran; Suhaimi, Nur-Afidah Mohamed; Vo, Jess H; Tai, Joyce A; Tan, Joanna H; Chua, Clarinda; Ten, Rachel; Lim, Wan Jun; Chew, Min Hoe; Hauser, Charlotte A E; van Dam, Rob M; Lim, Wei-Yen; Prabhakar, Shyam; Lim, Bing; Koh, Poh Koon; Robson, Paul; Ying, Jackie Y; Hillmer, Axel M; Tan, Min-Han

    2016-06-29

    Clusters of tumor cells are often observed in the blood of cancer patients. These structures have been described as malignant entities for more than 50 years, although their comprehensive characterization is lacking. Contrary to current consensus, we demonstrate that a discrete population of circulating cell clusters isolated from the blood of colorectal cancer patients are not cancerous but consist of tumor-derived endothelial cells. These clusters express both epithelial and mesenchymal markers, consistent with previous reports on circulating tumor cell (CTC) phenotyping. However, unlike CTCs, they do not mirror the genetic variations of matched tumors. Transcriptomic analysis of single clusters revealed that these structures exhibit an endothelial phenotype and can be traced back to the tumor endothelium. Further results show that tumor-derived endothelial clusters do not form by coagulation or by outgrowth of single circulating endothelial cells, supporting a direct release of clusters from the tumor vasculature. The isolation and enumeration of these benign clusters distinguished healthy volunteers from treatment-naïve as well as pathological early-stage (≤IIA) colorectal cancer patients with high accuracy, suggesting that tumor-derived circulating endothelial cell clusters could be used as a means of noninvasive screening for colorectal cancer. In contrast to CTCs, tumor-derived endothelial cell clusters may also provide important information about the underlying tumor vasculature at the time of diagnosis, during treatment, and throughout the course of the disease. PMID:27358499

  18. Upregulation of nemo-like kinase is an independent prognostic factor in colorectal cancer

    PubMed Central

    Zhang, Wei; He, Jian; Du, Yan; Gao, Xian-Hua; Liu, Yan; Liu, Qi-Zhi; Chang, Wen-Jun; Cao, Guang-Wen; Fu, Chuan-Gang

    2015-01-01

    AIM: To investigate the expression and oncogenic role of nemo-like kinase (NLK) in colorectal cancer. METHODS: Expression of NLK protein was assessed by immunohistochemistry in tissue specimens from 56 cases of normal colorectal mucosa, 51 cases of colorectal adenoma, and 712 cases of colorectal cancer. In addition, NLK expression was knocked down using a lentivirus carrying NLK small hairpin RNA in colorectal cancer cells. Cell viability methylthiazoletetrazolium assays, colony formation assays, flow cytometry cell cycle assays, Transwell migration assays, and gene expression assays were performed to explore its role on proliferation and migration of colorectal cancer. RESULTS: Expression of NLK protein progressively increased in tissues from the normal mucosa through adenoma to various stages of colorectal cancer. Overexpression of NLK protein was associated with advanced tumor-lymph node-metastasis stages, poor differentiation, lymph node and distant metastases, and a higher recurrence rate of colorectal cancer (P < 0.05). Multivariate analyses showed that NLK expression was an independent prognostic factor to predict overall survival (hazard ratio 2.57, 95% confidence interval: 1.66-3.98; P < 0.001) and disease-free survival (hazard ratio 1.96, 95% confidence interval: 1.40-2.74: P < 0.001) of colorectal cancer patients. Furthermore, knockdown of NLK expression in colorectal cancer cell lines reduced cell viability, colony formation, and migration, and arrested tumor cells at the G0/G1 phase of the cell cycle. At the gene level, knockdown of NLK expression inhibited matrix metalloproteinase-2 expression in colorectal cancer cells. CONCLUSION: NLK overexpression is an independent prognostic factor in colorectal cancer and knockdown of NLK expression inhibits colorectal cancer progression and metastasis. PMID:26269673

  19. 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

  20. Genistein suppresses FLT4 and inhibits human colorectal cancer metastasis.

    PubMed

    Xiao, Xiao; Liu, Zhiguo; Wang, Rui; Wang, Jiayin; Zhang, Song; Cai, Xiqiang; Wu, Kaichun; Bergan, Raymond C; Xu, Li; Fan, Daiming

    2015-02-20

    Dietary consumption of genistein, found in soy, has been associated with a potentially protective role in colorectal cancer (CRC) development and progression. Herein we demonstrate that genistein will inhibit human CRC cell invasion and migration, that it does so at non-cytotoxic concentrations and we demonstrate this in multiple human CRC cell lines. After orthotopic implantation of human CRC tumors into mice, oral genistein did not inhibit tumor growth, but did inhibit distant metastasis formation, and was non-toxic to mice. Using a qPCR array, we screened for genistein-induced changes in gene expression, followed by Western blot confirmation, demonstrating that genistein downregulated matrix metalloproteinase 2 and Fms-Related Tyrosine Kinase 4 (FLT4; vascular endothelial growth factor receptor 3). After demonstrating that genistein suppressed neo-angiogenesis in mouse tumors, we examined FLT4 expression in primary CRC and adjacent normal colonic tissue from 60 human subjects, demonstrating that increased FLT4 significantly correlates with increased stage and decreased survival. In summary, we demonstrate for the first time that genistein inhibits human CRC metastasis at dietary, non-toxic, doses. FLT4 is identified as a marker of metastatic disease, and as a response marker for small molecule therapeutics that inhibit CRC metastasis. PMID:25605009

  1. Colorectal cancer desmoplastic reaction up-regulates collagen synthesis and restricts cancer cell invasion.

    PubMed

    Coulson-Thomas, Vivien J; Coulson-Thomas, Yvette M; Gesteira, Tarsis F; de Paula, Cláudia A A; Mader, Ana M; Waisberg, Jaques; Pinhal, Maria A; Friedl, Andreas; Toma, Leny; Nader, Helena B

    2011-11-01

    During cancer cell growth many tumors exhibit various grades of desmoplasia, unorganized production of fibrous or connective tissue, composed mainly of collagen fibers and myofibroblasts. The accumulation of an extracellular matrix (ECM) surrounding tumors directly affects cancer cell proliferation, migration and spread; therefore the study of desmoplasia is of vital importance. Stromal fibroblasts surrounding tumors are activated to myofibroblasts and become the primary producers of ECM during desmoplasia. The composition, density and organization of this ECM accumulation play a major role on the influence desmoplasia has upon tumor cells. In this study, we analyzed desmoplasia in vivo in human colorectal carcinoma tissue, detecting an up-regulation of collagen I, collagen IV and collagen V in human colorectal cancer desmoplastic reaction. These components were then analyzed in vitro co-cultivating colorectal cancer cells (Caco-2 and HCT116) and fibroblasts utilizing various co-culture techniques. Our findings demonstrate that direct cell-cell contact between fibroblasts and colorectal cancer cells evokes an increase in ECM density, composed of unorganized collagens (I, III, IV and V) and proteoglycans (biglycan, fibromodulin, perlecan and versican). The desmoplastic collagen fibers were thick, with an altered orientation, as well as deposited as bundles. This increased ECM density inhibited the migration and invasion of the colorectal tumor cells in both 2D and 3D co-culture systems. Therefore this study sheds light on a possible restricting role desmoplasia could play in colorectal cancer invasion. PMID:21987222

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

    PubMed

    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

    2016-02-01

    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

  3. 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

  4. miR-183 regulates autophagy and apoptosis in colorectal cancer through targeting of UVRAG

    PubMed Central

    Su, Xiaomin; Li, Linqiang; Du, Zhimin; Hu, Meiyu; Dong, Yuechao; Bai, Xue; Liu, Tianyi; Yang, Baofeng; Shan, Hongli

    2016-01-01

    Ultraviolet radiation resistance-associated gene (UVRAG) is a well-known regulator of autophagy by promoting autophagosome formation and maturation. Multiple studies have implicated UVRAG in the pathogenesis of colorectal cancer. However, the mechanisms underlying the regulation of UVRAG are unclear. Here, we describe miR-183 as a new autophagy-inhibiting miRNA. Our results showed that induction of autophagy lead to down-regulation of miR-183 in colorectal cancer cells. And, over-expression of miR-183 resulted in the attenuation of rapamycin- or starvation-induced autophagy in cancer cells, whereas inhibition of endogenous miR-183 stimulated autophagy and apoptosis. Additionally, either autophagy inhibitor 3-MA or pan-caspase inhibitor Z-VAD-FMK respectively or both treatments reversed AMO-183-induced cell death. Further studies showed that UVRAG is a target of miR-183 and as a key regulator promotes autophagy and apoptosis. More importantly, over-expression of UVRAG rescued autophagic activity and induced apoptosis in presence of miR-183. Therefore, the present study investigated the promoting effect of miR-183 on colorectal cancer progression, which was considered to be mediated by autophagy and apoptosis through targeting of UVRAG. PMID:26717041

  5. 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.

  6. 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

  7. Pulmonary nodules and metastases in colorectal cancer.

    PubMed

    Nordholm-Carstensen, Andreas

    2016-01-01

    Patients with newly diagnosed colorectal cancer (CRC) are subjected to a preoperative thoraco-abdominal CT scan to determine the cancer stage. This staging is of relevance with regard to treatment and prognosis. About 20% of the patients have distant metastatic spread at the time of diagnosis, i.e. synchronous metastases. Most common are hepatic metastases followed by pulmonary involvement. The optimal staging modality for detecting synchronous pulmonary metastases is debated. It has been argued, that synchronous pulmonary metastases (SPCM) are rare in CRC and that the consequence of detecting SPCM is minimal. Furthermore, the current staging practice is complicated by a high number of incidental findings on the thoracic CT, so-called indeterminate pulmonary nodules (IPN). IPN can potentially represent SPCM. The purpose of this thesis was to estimate the prevalence, characteristics and clinical significance of IPN and SPCM detected at the primary staging in CRC. Study I was a systematic review of published studies on IPN in CRC focusing on the prevalence and radiological characteristics of IPN proving to be malignant. This knowledge would be of value in management strategies for IPN. On average 9% of all patients staged with a thoracic CT had IPN, however, the prevalence varied significantly between patients series. This was mainly attributed to varying/lacking definitions on IPN and variable radiological expertise in the assessment of the scans. Data were too inconsistently reported in the case series for a robust statement to be made on potential radiological characteristics suggestive of malignancy in IPN. Lymph node metastasis was the most common clinicopathological finding associated with malignancy of IPN. In conclusion, one patient of every 100 scanned patients had an IPN proving to a SPCM at follow-up, but we found no evidence that IPN should result in intensified diagnostic work-up besides routine follow-up for CRC. Study II was an analysis of the

  8. 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.

  9. A Trial of Three Interventions to Promote Colorectal Cancer Screening in African Americans

    PubMed Central

    Smith, Selina A.; Majett, Charlye D.; Alema-Mensah, Ernest

    2009-01-01

    Background Colorectal cancer (CRC) is the second-leading cause of cancer death in the U.S. CRC incidence and mortality rates are higher in blacks than in whites and screening rates are lower in blacks than in whites. We tested three interventions intended to increase the rate of colorectal cancer screening among African Americans. Methods The interventions were chosen to address evidence gaps in the Guide to Community Preventive Services: one-on-one education, group education, and reducing out-of-pocket costs. Three hundred sixty-nine African American men and women aged ≥50 years were enrolled in this randomized controlled community intervention trial. The main outcome measures were post-intervention increase in colorectal cancer knowledge and obtaining a screening test within six months. Results There was substantial attrition: 257 participants completed the intervention and were available for follow-up 3–6 months later. Among completers, there were significant increases in knowledge in both educational cohorts but in neither of the other two. By the 6 month follow-up, 17.7% (11/62) of control group members reported having undergone screening, as compared to 33.9% (22/65) of the group education cohort (p = 0.039). Screening rate increases in the other 2 cohorts were not statistically significant. Conclusions Group education can increase colorectal cancer screening rates among African Americans. The screening rate of less than 35% in a group of people who participated in an educational program through multiple sessions over a period of several weeks indicates that there are still barriers to overcome. PMID:20052732

  10. Novel therapeutic agents in the treatment of metastatic colorectal cancer

    PubMed Central

    Pai, Sachin Gopalkrishna; Fuloria, Jyotsna

    2016-01-01

    Over the past couple of decades considerable progress has been made in the management of metastatic colorectal cancers (mCRC) leading to a significant improvement in five-year survival. Although part of this success has been rightly attributed to aggressive surgical management and advances in other adjunct treatments, our understanding of the pathogenesis of cancer and emergence of newer molecular targets for colon cancer has created a powerful impact. In this review article we will discuss various targeted therapies in the management of mCRC. Newer agents on the horizon soon to be incorporated in clinical practice will be briefly reviewed as well. PMID:26798440

  11. Clinical applications of next-generation sequencing in colorectal cancers

    PubMed Central

    Kim, Tae-Min; Lee, Sug-Hyung; Chung, Yeun-Jun

    2013-01-01

    Like other solid tumors, colorectal cancer (CRC) is a genomic disorder in which various types of genomic alterations, such as point mutations, genomic rearrangements, gene fusions, or chromosomal copy number alterations, can contribute to the initiation and progression of the disease. The advent of a new DNA sequencing technology known as next-generation sequencing (NGS) has revolutionized the speed and throughput of cataloguing such cancer-related genomic alterations. Now the challenge is how to exploit this advanced technology to better understand the underlying molecular mechanism of colorectal carcinogenesis and to identify clinically relevant genetic biomarkers for diagnosis and personalized therapeutics. In this review, we will introduce NGS-based cancer genomics studies focusing on those of CRC, including a recent large-scale report from the Cancer Genome Atlas. We will mainly discuss how NGS-based exome-, whole genome- and methylome-sequencing have extended our understanding of colorectal carcinogenesis. We will also introduce the unique genomic features of CRC discovered by NGS technologies, such as the relationship with bacterial pathogens and the massive genomic rearrangements of chromothripsis. Finally, we will discuss the necessary steps prior to development of a clinical application of NGS-related findings for the advanced management of patients with CRC. PMID:24187453

  12. 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

  13. Vitamin D and colorectal cancer: molecular, epidemiological and clinical evidence.

    PubMed

    Dou, Ruoxu; Ng, Kimmie; Giovannucci, Edward L; Manson, JoAnn E; Qian, Zhi Rong; Ogino, Shuji

    2016-05-01

    In many cells throughout the body, vitamin D is converted into its active form calcitriol and binds to the vitamin D receptor (VDR), which functions as a transcription factor to regulate various biological processes including cellular differentiation and immune response. Vitamin D-metabolising enzymes (including CYP24A1 and CYP27B1) and VDR play major roles in exerting and regulating the effects of vitamin D. Preclinical and epidemiological studies have provided evidence for anti-cancer effects of vitamin D (particularly against colorectal cancer), although clinical trials have yet to prove its benefit. In addition, molecular pathological epidemiology research can provide insights into the interaction of vitamin D with tumour molecular and immunity status. Other future research directions include genome-wide research on VDR transcriptional targets, gene-environment interaction analyses and clinical trials on vitamin D efficacy in colorectal cancer patients. In this study, we review the literature on vitamin D and colorectal cancer from both mechanistic and population studies and discuss the links and controversies within and between the two parts of evidence. PMID:27245104

  14. Colorectal Cancer Screening in an Equal Access Healthcare System

    PubMed Central

    DeBarros, Mia; Steele, Scott R.

    2013-01-01

    Introduction: The military health system (MHS) a unique setting to analyze implementation programs as well as outcomes for colorectal cancer (CRC). Here we look at the efficacy of different CRC screening methods, attributes and results within the MHS, and current barriers to increase compliance. Materials and Methods: A literature search was conducted utilizing PubMed and the Cochrane library. Key-word combinations included colorectal cancer screening, racial disparity, risk factors, colorectal cancer, screening modalities, and randomized control trials. Directed searches were also performed of embedded references. Results: Despite screening guidelines from several national organizations, extensive barriers to widespread screening remain, especially for minority populations. These barriers are diverse, ranging from education and access problems to personal beliefs. Screening rates in MHS have been reported to be generally higher at 71% compared to national averages of 50-65%. Conclusion: CRC screening can be highly effective at improving detection of both pre-malignant and early cancers. Improved patient education and directed efforts are needed to improve CRC screening both nationally and within the MHS. PMID:23459768

  15. Early-onset colorectal cancer: A separate subset of colorectal cancer

    PubMed Central

    Silla, Irene Osorio; Rueda, Daniel; Rodríguez, Yolanda; García, Juan Luis; de la Cruz Vigo, Felipe; Perea, José

    2014-01-01

    Colorectal cancer (CRC) has a great impact on the world population. With increasing frequency, CRC is described according to the presenting phenotype, based on its molecular characteristics. Classification of CRC tumors according to their genetic and/or epigenetic alterations is not only important for establishing the molecular bases of the disease, but also for predicting patient outcomes and developing more individualized treatments. Early-onset CRC is a heterogeneous disease, with a strong familial component, although the disease is sporadic in an important proportion of cases. Different molecular alterations appear to contribute to the apparent heterogeneity of the early-onset population and subgroups can be distinguished with distinct histopathologic and familial characteristics. Moreover, compared with late-onset CRC, there are characteristics that suggest that early-onset CRC may have a different molecular basis. The purpose of this review was to analyze the current state of knowledge about early-onset CRC with respect to clinicopathologic, familial and molecular features. Together, these features make it increasingly clear that this subset of CRC may be a separate disease, although it has much in common with late-onset CRC. PMID:25516639

  16. 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. PMID:25846122

  17. 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…

  18. Discovery and validation of the antimetastatic activity of citalopram in colorectal cancer.

    PubMed

    Iskar, Murat; Bork, Peer; van Noort, Vera

    2015-01-01

    Inverse gene expression profiling was recently shown to help drug repositioning. We showed that this approach works best for cancer and predicted novel drug candidates that may reduce metastasis in colorectal cancer. Antimetastatic activity of our predicted candidate, citalopram, was validated in an orthotopic mouse model of metastatic colorectal cancer. PMID:27308430

  19. Discovery and validation of the antimetastatic activity of citalopram in colorectal cancer

    PubMed Central

    Iskar, Murat

    2015-01-01

    Inverse gene expression profiling was recently shown to help drug repositioning. We showed that this approach works best for cancer and predicted novel drug candidates that may reduce metastasis in colorectal cancer. Antimetastatic activity of our predicted candidate, citalopram, was validated in an orthotopic mouse model of metastatic colorectal cancer. PMID:27308430

  20. Chemotherapeutic implications in microsatellite unstable colorectal cancer1

    PubMed Central

    Jo, Won-Seok; Carethers, John M.

    2016-01-01

    Chemotherapy for colorectal cancer is currently offered to patients based on the stage of their cancer, and there is evidence to show an overall survival benefit with 5-fluorouracil-based (5-FU) therapy for patients with lymph node metastasis who receive it. The pathogenesis of colorectal cancer involves genomic instability, with about 15% of tumors demonstrating a form of genomic instability called high-frequency microsatellite instability (MSI-H) and due to loss of DNA mismatch repair function, and the remainder of colorectal tumors lacking MSI-H with retained DNA mismatch repair function and called microsatellite stable (MSS), with a large proportion of these tumors demonstrating another form of genomic instability called chromosomal instability. There is now evidence to show that the form of genomic instability that is present in a patient’s colorectal cancer may predict a survival benefit from 5-FU. In particular, patients whose colorectal tumors have MSI-H do not gain a survival benefit with 5-FU as compared to patients with MSS tumors. In vitro evidence supports these findings, as MSI-H colon cancer cell lines are more resistant to 5-FU compared to MSS cell lines. More specifically, components of the DNA mismatch repair system have been shown to recognize and bind to 5-FU that becomes incorporated into DNA and which could be a trigger to induce cell death. The binding and subsequent cell death events would be absent in colorectal tumors with MSI-H, which have lost intact DNA mismatch repair function. These findings suggest that: (a) tumor cytotoxicity of 5-FU is mediated by DNA mechanisms in addition to well-known RNA mechanisms, and (b) patients whose tumors demonstrate MSI-H may not benefit from 5-FU therapy. Future studies should include a better understanding of the cellular mechanisms of the DNA recognition of 5-FU, multi-centered prospective trials investigating the survival benefit of 5-FU based on genomic instability, and the investigation of

  1. Symptom Prevalence in Lung and Colorectal Cancer Patients

    PubMed Central

    Walling, Anne M.; Weeks, Jane C.; Kahn, Katherine L.; Tisnado, Diana; Keating, Nancy L.; Dy, Sydney M.; Arora, Neeraj K.; Mack, Jennifer W.; Pantoja, Philip M.; Malin, Jennifer L.

    2014-01-01

    Context Relatively few data are available about symptoms among cancer patients. Objectives To describe the prevalence and severity of symptoms among a large, representative cohort of newly diagnosed cancer patients. Methods We collected survey data about symptoms (pain, fatigue, depression, nausea/vomiting, cough, dyspnea, diarrhea) from 5422 patients with incident lung and colorectal cancer from the diverse, nationally representative Cancer Care Outcomes Research and Surveillance (CanCORs) Consortium cohort. We described the prevalence of any symptoms and moderate/severe symptoms approximately four to six months following diagnosis. We used logistic regression to identify patient and clinical characteristics associated with symptoms, and calculated adjusted proportions of patients with symptoms. Results In total, 5067 (93.5%) patients reported at least one symptom in the four weeks before their survey, with 51% reporting at least one moderate/severe symptom. Lung cancer patients reported more symptoms than colorectal cancer patients. Patients who received treatment or had more comorbidities were more likely to report symptoms. For example, after adjustment, patients who received chemotherapy during the six weeks before the survey were more likely than others to report at least one symptom (97.3% vs. 90.8%, P<0.001), and at least one moderate/severe symptom (56.8% vs. 46.2%, P<0.001). After adjustment, early vs. late stage patients did not differ in reports of at least one symptom (93.6% vs. 93.4%, P=0.853) and differed only slightly in reports of at least one moderate/severe symptom (53.3% vs. 49.6%, P=0.009). Conclusion Most recently diagnosed lung and colorectal cancer patients have cancer-related symptoms regardless of stage, and more than half have at least one moderate/severe symptom. PMID:24973624

  2. Radiation risks associated with serial imaging in colorectal cancer patients: Should we worry?

    PubMed Central

    Oh, Jeong Suk; Koea, Jonathan B

    2014-01-01

    To provide an overview of the radiation related cancer risk associated with multiple computed tomographic scans required for follow up in colorectal cancer patients. A literature search of the PubMed and Cochrane Library databases was carried out and limited to the last 10 years from December 2012. Inclusion criteria were studies where computed tomographic scans or radiation from other medical imaging modalities were used and the risks associated with ionizing radiation reported. Thirty-six studies were included for appraisal with no randomized controlled trials. Thirty-four of the thirty-six studies showed a positive association between medical imaging radiation and increased risk of cancer. The radiation dose absorbed and cancer risk was greater in children and young adults than in older patients. Most studies included in the review used a linear, no-threshold model to calculate cancer risks and this may not be applicable at low radiation doses. Many studies are retrospective and ensuring complete follow up on thousands of patients is difficult. There was a minor increased risk of cancer from ionizing radiation in medical imaging studies. The radiation risks of low dose exposure (< 50 milli-Sieverts) are uncertain. A clinically justified scan in the context of colorectal cancer is likely to provide more benefits than harm but current guidelines for patient follow up will need to be revised to accommodate a more aggressive approach to treating metastatic disease. PMID:24415862

  3. Oncolytic vaccinia virus synergizes with irinotecan in colorectal cancer.

    PubMed

    Ottolino-Perry, Kathryn; Acuna, Sergio A; Angarita, Fernando A; Sellers, Clara; Zerhouni, Siham; Tang, Nan; McCart, J Andrea

    2015-10-01

    Metastatic colorectal cancer (CRC) is complex clinical challenge for which there are limited treatment options. Chemotherapy with or without surgery provides moderate improvements in overall survival and quality of life; nevertheless the 5-year survival remains below 30%. Oncolytic vaccinia virus (VV) shows strong anti-tumour activity in models of CRC, however transient delays in disease progression are insufficient to lead to long-term survival. Here we examined the efficacy of VV with oxaliplatin or SN-38 (active metabolite of irinotecan) in CRC cell lines in vitro and VV with irinotecan in an orthotopic model of metastatic CRC. Synergistic improvements in in vitro cell killing were observed in multiple cell lines. Combination therapy was well tolerated in tumour-bearing mice and the median survival was significantly increased relative to monotherapy despite a drug-dependent decrease in the mean tumour titer. Increased apoptosis following in vitro and in vivo combination therapy was observed. In vitro cell cycle analysis showed increases in S-phase cells following infection occurred in both infected and uninfected cell populations. This corresponded to a 4-fold greater increase in apoptosis in the uninfected compared to infected cells following combination therapy. Combination treatment strategies are among the best options for patients with advanced cancers. VV is currently under clinical investigation in patients with CRC and the data presented here suggest that its combination with irinotecan may provide benefit to a subset of CRC patients. Further, investigation of this combination is necessary to determine the tumour characteristics responsible for mediating synergy. PMID:26004084

  4. 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.

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

    PubMed Central

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

    2016-01-01

    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. PMID:24632202

  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. Liver resection for colorectal cancer metastases

    PubMed Central

    Gallinger, S.; Biagi, J.J.; Fletcher, G.G.; Nhan, C.; Ruo, L.; McLeod, R.S.

    2013-01-01

    Questions Should surgery be considered for colorectal cancer (crc) patients who have liver metastases plus (a) pulmonary metastases, (b) portal nodal disease, or (c) other extrahepatic metastases (ehms)? What is the role of chemotherapy in the surgical management of crc with liver metastases in (a) patients with resectable disease in the liver, or (b) patients with initially unresectable disease in the liver that is downsized with chemotherapy (“conversion”)? What is the role of liver resection when one or more crc liver metastases have radiographic complete response (rcr) after chemotherapy? Perspectives Advances in chemotherapy have improved survival in crc patients with liver metastases. The 5-year survival with chemotherapy alone is typically less than 1%, although two recent studies with folfox or folfoxiri (or both) reported rates of 5%–10%. However, liver resection is the treatment that is most effective in achieving long-term survival and offering the possibility of a cure in stage iv crc patients with liver metastases. This guideline deals with the role of chemotherapy with surgery, and the role of surgery when there are liver metastases plus ehms. Because only a proportion of patients with crc metastatic disease are considered for liver resection, and because management of this patient population is complex, multidisciplinary management is required. Methodology Recommendations in the present guideline were formulated based on a prepublication version of a recent systematic review on this topic. The draft methodology experts, and external review by clinical practitioners. Feedback was incorporated into the final version of the guideline. Practice Guideline These recommendations apply to patients with liver metastases from crc who have had or will have a complete (R0) resection of the primary cancer and who are being considered for resection of the liver, or liver plus specific and limited ehms, with curative intent. 1(a). Patients with liver and lung

  8. Effects of Progressive Muscle Relaxation Therapy in Colorectal Cancer Patients.

    PubMed

    Kim, Kyeng Jin; Na, Yeon Kyung; Hong, Hae Sook

    2016-08-01

    This study aimed to examine the effect of progressive muscle relaxation therapy (PMRT) on cortisol level, the Stress Arousal Checklist (SACL) score, blood pressure, and heart rate in colorectal cancer patients undergoing laparoscopic surgery. Forty-six patients were divided into control and experimental groups. Cortisol levels, blood pressure, and heart rate were measured before surgery and between 8:00 and 11:00 a.m. on the first, third, and fifth days after surgery. SACL score was measured before surgery and on the fifth day after surgery at the same time points. PMRT was performed twice a day for 5 days. Analyses of covariance with advanced covariate levels and t tests showed that PMRT helps colorectal cancer patients achieve a lower stress response and provides an important basis for stress control. PMID:26945016

  9. Prediction of colorectal cancer diagnosis based on circulating plasma proteins.

    PubMed

    Surinova, Silvia; Choi, Meena; Tao, Sha; Schüffler, Peter J; Chang, Ching-Yun; Clough, Timothy; Vysloužil, Kamil; Khoylou, Marta; Srovnal, Josef; Liu, Yansheng; Matondo, Mariette; Hüttenhain, Ruth; Weisser, Hendrik; Buhmann, Joachim M; Hajdúch, Marián; Brenner, Hermann; Vitek, Olga; Aebersold, Ruedi

    2015-09-01

    Non-invasive detection of colorectal cancer with blood-based markers is a critical clinical need. Here we describe a phased mass spectrometry-based approach for the discovery, screening, and validation of circulating protein biomarkers with diagnostic value. Initially, we profiled human primary tumor tissue epithelia and characterized about 300 secreted and cell surface candidate glycoproteins. These candidates were then screened in patient systemic circulation to identify detectable candidates in blood plasma. An 88-plex targeting method was established to systematically monitor these proteins in two large and independent cohorts of plasma samples, which generated quantitative clinical datasets at an unprecedented scale. The data were deployed to develop and evaluate a five-protein biomarker signature for colorectal cancer detection. PMID:26253081

  10. A novel antimetabolite: TAS-102 for metastatic colorectal cancer.

    PubMed

    Miyamoto, Yuji; Lenz, Heinz-Josef; Baba, Hideo

    2016-01-01

    TAS-102 is a new oral anti-tumor drug, composed of a thymidine-based nucleoside analog (trifluridine: FTD) and a thymidine phosphorylase inhibitor (tipiracil hydrochloride: TPI). TAS-102 has been shown to significantly improve overall survival and progression-free survival in patients with refractory metastatic colorectal cancer (mCRC) in placebo-controlled randomized phase II and III trials. The current review summarizes mechanisms of action, pharmacokinetics/dynamics and preclinical and clinical data of TAS-102 in colorectal cancer. TAS-102 is a new salvage-line treatment option for patients with mCRC. TAS-102 is well tolerated and has great potential in future clinical drug combination therapies. PMID:26677869

  11. Mouse models for the discovery of colorectal cancer driver genes

    PubMed Central

    Clark, Christopher R; Starr, Timothy K

    2016-01-01

    Colorectal cancer (CRC) constitutes a major public health problem as the third most commonly diagnosed and third most lethal malignancy worldwide. The prevalence and the physical accessibility to colorectal tumors have made CRC an ideal model for the study of tumor genetics. Early research efforts using patient derived CRC samples led to the discovery of several highly penetrant mutations (e.g., APC, KRAS, MMR genes) in both hereditary and sporadic CRC tumors. This knowledge has enabled researchers to develop genetically engineered and chemically induced tumor models of CRC, both of which have had a substantial impact on our understanding of the molecular basis of CRC. Despite these advances, the morbidity and mortality of CRC remains a cause for concern and highlight the need to uncover novel genetic drivers of CRC. This review focuses on mouse models of CRC with particular emphasis on a newly developed cancer gene discovery tool, the Sleeping Beauty transposon-based mutagenesis model of CRC. PMID:26811627

  12. Biomedical imaging of colorectal cancer by near infrared fluorescent nanoparticles.

    PubMed

    Tivony, Ran; Larush, Liraz; Sela-Tavor, Osnat; Magdassi, Shlomo

    2014-06-01

    In this paper we describe the preparation of novel Near Infrared (NIR) fluorescent nanoparticles for application in medical imaging of colorectal tumors. The nanoparticles are prepared by using only non-covalent binding processes of molecules which are approved for clinical use. The preparation process is based on the precipitation of a polycation, Eudragit-RS, followed by sequential adsorption of a blocking protein, sodium caseinate, NIR fluorescent dye, Indocyanine Green (ICG) and optionally, a targeting molecule, anti-CEA antibody. Fluorescence measurements have shown that these nanoparticles have higher resistance to photobleaching and higher quantum yield relatively to free ICG. Imaging experiments in orthotopic colorectal cancer mice models have shown that these fluorescent nanoparticles are capable of binding to LS174T human colon tumors in vivo with high specificity, even without the targeting molecule. These nanoparticles, composed of all FDA approved materials, open the way to clinical bioimaging and diagnostics of colon cancer. PMID:24749398

  13. Chemoresistive Gas Sensors for the Detection of Colorectal Cancer Biomarkers

    PubMed Central

    Malagù, Cesare; Fabbri, Barbara; Gherardi, Sandro; Giberti, Alessio; Guidi, Vincenzo; Landini, Nicolò; Zonta, Giulia

    2014-01-01

    Numerous medical studies show that tumor growth is accompanied by protein changes that may lead to the peroxidation of the cell membrane with consequent emission of volatile organic compounds (VOCs) by breath or intestinal gases that should be seen as biomarkers for colorectal cancer (CRC). The analysis of VOCs represents a non-invasive and potentially inexpensive preliminary screening technique. An array of chemoresistive gas sensors based on screen-printed metal oxide semiconducting films has been selected to discriminate gases of oncological interest, e.g., 1-iodononane and benzene, widely assumed to be biomarkers of colorectal cancer, from those of interference in the gut, such as methane and nitric oxide. PMID:25313496

  14. Mouse models of colorectal cancer as preclinical models

    PubMed Central

    Buczacki, Simon J.A.; Arends, Mark J.; Adams, David J.

    2015-01-01

    In this review, we discuss the application of mouse models to the identification and pre‐clinical validation of novel therapeutic targets in colorectal cancer, and to the search for early disease biomarkers. Large‐scale genomic, transcriptomic and epigenomic profiling of colorectal carcinomas has led to the identification of many candidate genes whose direct contribution to tumourigenesis is yet to be defined; we discuss the utility of cross‐species comparative ‘omics‐based approaches to this problem. We highlight recent progress in modelling late‐stage disease using mice, and discuss ways in which mouse models could better recapitulate the complexity of human cancers to tackle the problem of therapeutic resistance and recurrence after surgical resection. PMID:26115037

  15. Colorectal cancer and dysplasia in inflammatory bowel disease.

    PubMed

    Zisman, Timothy L; Rubin, David T

    2008-05-01

    Both ulcerative colitis and Crohn's disease carry an increased risk of developing colorectal cancer. Established risk factors for cancer among patients with inflammatory bowel disease (IBD) include the younger age at diagnosis, greater extent and duration of disease, increased severity of inflammation, family history of colorectal cancer and coexisting primary sclerosing cholangitis. Recent evidence suggests that current medical therapies and surgical techniques for inflammatory bowel disease may be reducing the incidence of this complication. Nonetheless heightened vigilance and a careful, comprehensive approach to prevent or minimize the complications of invasive cancer are warranted in this unique cohort of patients. Current guidelines for the prevention and early detection of cancer in this high risk population are grounded in the concept of an inflammation-dysplasia-carcinoma sequence. A thorough understanding of the definition and natural history of dysplasia in IBD, as well as the challenges associated with detection and interpretation of dysplasia are fundamental to developing an effective strategy for surveillance and prevention, and understanding the limitations of the current approach to prevention. This article reviews the current consensus guidelines for screening and surveillance of cancer in IBD, as well as presenting the evidence and rationale for chemoprevention of cancer and a discussion of emerging technologies for the detection of dysplasia. PMID:18461651

  16. 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

    2016-01-01

    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

  17. 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

  18. [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

  19. Laparoscopic subtotal colectomy for synchronous triple colorectal cancer: A case report

    PubMed Central

    Jiang, Xuetong; Xu, Chuanqi; Tang, Dong; Wang, Daorong

    2016-01-01

    Synchronous colorectal cancers refer to the simultaneous occurrence of multiple colorectal tumors in a single patient, excluding any metastases from other organs. At present, radical surgery is considered the standard curative treatment; however, individualized surgical strategies depend on tumor location, the depth of invasion and the general health of the patient. In the present study, the case of a 52-year-old man who presented with a 2-month history of abdominal pain that was accompanied by intermittent hematochezia and weight loss is reported. The patient had no family history of cancer. Computed tomography (CT) of the abdomen revealed intestinal wall thickness in the transverse colon and volvulus in the hepatic flexure of colon. Colonoscopy identified 3 tumors: The first tumor was located in the descending colon with lumen stenosis ~60 cm from the anal verge, the second tumor was located in the hepatic flexure of the colon, and the third tumor was located in the sigmoid colon, 23 cm from the anal verge. Subsequently, laparoscopic subtotal colectomy was performed and all three tumors were removed, and the diagnosis was confirmed by histopathological examination. The patient did not undergo chemotherapy following surgery, due to personal reasons. Subsequent to 19 months of follow-up examinations using CT and colonoscopy every 6 months, the patient exhibited no signs of recurrence. Thus, laparoscopic subtotal colectomy represents an effective surgical approach for the treatment of synchronous colorectal cancer following imaging and endoscopic diagnosis. PMID:27446464

  20. A Survival Association Study of 102 Polymorphisms Previously Associated with Survival Outcomes in Colorectal Cancer

    PubMed Central

    Xu, Jingxiong; Werdyani, Salem; Shestopaloff, Konstantin; Dicks, Elizabeth; Green, Jane; Parfrey, Patrick; Green, Roger

    2015-01-01

    Several published studies identified associations of a number of polymorphisms with a variety of survival outcomes in colorectal cancer. In this study, we aimed to explore 102 previously reported common genetic polymorphisms and their associations with overall survival (OS) and disease-free survival (DFS) in a colorectal cancer patient cohort from Newfoundland (n = 505). Genotypes were obtained using a genomewide SNP genotyping platform. For each polymorphism, the best possible genetic model was estimated for both overall survival and disease-free survival using a previously published approach. These SNPs were then analyzed under their genetic models by Cox regression method. Correction for multiple comparisons was performed by the False Discovery Rate (FDR) method. Univariate analysis results showed that RRM1-rs12806698, IFNGR1-rs1327474, DDX20-rs197412, and PTGS2-rs5275 polymorphisms were nominally associated with OS or DFS (p < 0.01). In stage-adjusted analysis, the nominal associations of DDX20-rs197412, PTGS2-rs5275, and HSPA5-rs391957 with DFS were detected. However, after FDR correction none of these polymorphisms remained significantly associated with the survival outcomes. We conclude that polymorphisms investigated in this study are not associated with OS or DFS in our colorectal cancer patient cohort. PMID:26064972

  1. Multiscale Model of Colorectal Cancer Using the Cellular Potts Framework

    PubMed Central

    Osborne, James M

    2015-01-01

    Colorectal cancer (CRC) is one of the major causes of death in the developed world and forms a canonical example of tumorigenesis. CRC arises from a string of mutations of individual cells in the colorectal crypt, making it particularly suited for multiscale multicellular modeling, where mutations of individual cells can be clearly represented and their effects readily tracked. In this paper, we present a multicellular model of the onset of colorectal cancer, utilizing the cellular Potts model (CPM). We use the model to investigate how, through the modification of their mechanical properties, mutant cells colonize the crypt. Moreover, we study the influence of mutations on the shape of cells in the crypt, suggesting possible cell- and tissue-level indicators for identifying early-stage cancerous crypts. Crucially, we discuss the effect that the motility parameters of the model (key factors in the behavior of the CPM) have on the distribution of cells within a homeostatic crypt, resulting in an optimal parameter regime that accurately reflects biological assumptions. In summary, the key results of this paper are 1) how to couple the CPM with processes occurring on other spatial scales, using the example of the crypt to motivate suitable motility parameters; 2) modeling mutant cells with the CPM; 3) and investigating how mutations influence the shape of cells in the crypt. PMID:26461973

  2. Colorectal cancer and immunity: What we know and perspectives

    PubMed Central

    Pernot, Simon; Terme, Magali; Voron, Thibault; Colussi, Orianne; Marcheteau, Elie; Tartour, Eric; Taieb, Julien

    2014-01-01

    Strong evidence supports the concept of immunosurveillance and immunoediting in colorectal cancer. In particular, the density of T CD8+ and CD45+ lymphocyte infiltration was recently shown to have a better prognostic value than the classic tumor node metastasis classification factor. Other immune subsets, as macrophages, natural killer cells or unconventionnal lymphocytes, seem to play an important role. Induction of regulatory T cells (Tregs) or immunosuppressive molecules such as PD-1 or CTLA-4 and downregulation of antigen-presenting molecules are major escape mechanisms to antitumor immune response. The development of these mechanisms is a major obstacle to the establishment of an effective immune response, but also to the use of immunotherapy. Although immunotherapy is not yet routinely used in colorectal cancer, we now know that most treatments used (chemotherapy and biotherapy) have immunomodulatory effects, such as induction of immunogenic cell death by chemotherapy, inhibition of immunosuppression by antiangiogenic agents, and antibody-dependent cytotoxicity induced by cetuximab. Finally, many immunotherapy strategies are being developed and tested in phase I to III clinical trials. The most promising strategies are boosting the immune system with cytokines, inhibition of immunoregulatory checkpoints, vaccination with vectorized antigens, and adoptive cell therapy. Comprehension of antitumor immune response and combination of the different approaches of immunotherapy may allow the use of effective immunotherapy for treatment of colorectal cancer in the near future. PMID:24833840

  3. Current status of pharmacological treatment of colorectal cancer

    PubMed Central

    Akhtar, Reyhan; Chandel, Shammy; Sarotra, Pooja; Medhi, Bikash

    2014-01-01

    AIM: To review the clinical trials for the development in drugs for chemotherapeutic treatment of colorectal cancer (CRC). METHODS: A systematic review identified randomized controlled trials (RCTs) assessing drugs for the treatment of CRC or adenomatous polyps from www.clinicaltrials.gov. Various online medical databases were searched for relevant publications. RESULTS: Combination treatment regimens of standard drugs with newer agents have been shown to improve overall survival, disease-free survival, time to progression and quality of life compared to that with standard drugs alone in patients with advanced colorectal cancer. The FOLFOXIRI regimen has been associated with a significantly higher response rate, progression-free survival and overall survival compared to the FOLFIRI regimen. CONCLUSION: Oxaliplatin plus intravenous bolus fluorouracil and leucovorin has been shown to be superior for disease-free survival when compared to intravenous bolus fluorouracil and leucovorin. In addition, oxaliplatin regimens were more likely to result in successful surgical resections. First line treatment with cetuximab plus fluorouracil, leucovorin and irinotecan has been found to reduce the risk of metastatic progression in patients with epidermal growth factor receptor-positive colorectal cancer with unresectable metastases. The addition of bevacizumab has been shown to significantly increase overall and progression-free survival when given in combination with standard therapy. PMID:24936228

  4. Heterogenous mismatch-repair status in colorectal cancer

    PubMed Central

    2014-01-01

    Abstract Background Immunohistochemical staining for mismatch repair proteins is efficient and widely used to identify mismatch repair defective tumors. The tumors typically show uniform and widespread loss of MMR protein staining. We identified and characterized colorectal cancers with alternative, heterogenous mismatch repair protein staining in order to delineate expression patterns and underlying mechanisms. Methods Heterogenous staining patterns that affected at least one of the mismatch repair proteins MLH1, PMS2, MSH2 and MSH6 were identified in 14 colorectal cancers. Based on alternative expression patterns macro-dissected and micro-dissected tumor areas were separately analyzed for microsatellite instability and MLH1 promoter methylation. Results Heterogenous retained/lost mismatch repair protein expression could be classified as intraglandular (within or in-between glandular formations), clonal (in whole glands or groups of glands) and compartmental (in larger tumor areas/compartments or in between different tumor blocks). These patterns coexisted in 9/14 tumors and in the majority of the tumors correlated with differences in microsatellite instability/MLH1 methylation status. Conclusions Heterogenous mismatch repair status can be demonstrated in colorectal cancer. Though rare, attention to this phenomenon is recommended since it corresponds to differences in mismatch repair status that are relevant for correct classification. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1771940323126788 PMID:24968821

  5. 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

  6. 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. |

  7. 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

  8. PDLIM1 Stabilizes the E-Cadherin/β-Catenin Complex to Prevent Epithelial-Mesenchymal Transition and Metastatic Potential of Colorectal Cancer Cells.

    PubMed

    Chen, Hai-Ning; Yuan, Kefei; Xie, Na; Wang, Kui; Huang, Zhao; Chen, Yan; Dou, Qianhui; Wu, Min; Nice, Edouard C; Zhou, Zong-Guang; Huang, Canhua

    2016-03-01

    Metastasis is a major cause of death in patients with colorectal cancer, and increasing evidence supports the contribution of the epithelial-mesenchymal transition (EMT) to cancer progression. The dissociation of the E-cadherin/β-catenin adhesion complex represents a key step in EMT and promotes cancer invasion and metastasis, but the upstream signaling pathways regulating this interaction are poorly understood. Here, we show that PDLIM1, a member of the PDZ and LIM protein family, was downregulated in highly metastatic colorectal cancer cells and liver metastases from colorectal cancer patients. We found that loss of PDLIM1 promoted the expression of EMT markers and increased the invasive and migratory properties of multiple colorectal cancer cell lines. Furthermore, PDLIM1 knockdown increased colon-derived liver metastasis in an orthotopic colorectal cancer model and promoted distant metastatic colonization in an experimental lung metastasis model. Mechanistic investigations revealed that PDLIM1 interacted with and stabilized the E-cadherin/β-catenin complex, thereby inhibiting the transcriptional activity of β-catenin and preventing EMT. Accordingly, PDLIM1 overexpression attenuated EMT of colorectal cancer cells. Moreover, the downregulation of PDLIM1 in colorectal cancer samples correlated with reduced E-cadherin and membrane β-catenin levels, and was associated with shorter overall survival. In conclusion, our study demonstrates that PDLIM1 suppresses EMT and metastatic potential of colorectal cancer cells by stabilizing β-catenin at cell-cell junctions, and its loss in metastatic tissues may represent a potential prognostic marker of aggressive disease. PMID:26701804

  9. 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

  10. 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

  11. 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

  12. Prognostic comparison between mucinous and nonmucinous adenocarcinoma in colorectal cancer.

    PubMed

    Park, Jong Seob; Huh, Jung Wook; Park, Yoon Ah; Cho, Yong Beom; Yun, Seong Hyeon; Kim, Hee Cheol; Lee, Woo Yong; Chun, Ho-Kyung

    2015-04-01

    Mucinous adenocarcinoma (MAC) is a histological subtype of colorectal cancer. The oncologic behavior of MAC differs from nonmucinous adenocarcinoma (non-MAC). Our aim in this study was to characterize patients with colorectal MAC through evaluation of a large, institutional-based cohort with long-term follow-up. A total of 6475 patients with stages I to III colorectal cancer who underwent radical surgery were enrolled from January 2000 to December 2010. Prognostic comparison between MAC (n = 274, 4.2%) and non-MAC was performed. The median follow-up period was 48.0 months. Patients with MAC were younger than those without MAC (P = 0.012) and had larger tumor size (P < 0.001), higher preoperative carcinoembryonic antigen (P < 0.001), higher pathologic T stage (P < 0.001), more right-sided colon cancer (49.3%, P < 0.001), and more frequent high-frequency microsatellite instability (10.2%, P < 0.001). Five-year disease-free survival (DFS) was 76.5% in the MAC group and 83.2% in the non-MAC group (P = 0.008), and 5-year overall survival was 81.4% versus 87.4%, respectively (P = 0.005). Mucinous histology (MAC vs non-MAC) in the entire cohort was not an independent prognostic factor of DFS but had a statistical tendency (P = 0.071). In subgroup analysis of colon cancer without rectal cancer, mucinous histology was an independent prognostic factor (P = 0.026). MAC was found at more advanced stage, located mainly at the right side and was an independent factor of survival in colon cancer. Because of the unique biological behavior of MAC, patients with MAC require special consideration during follow-up. PMID:25881840

  13. Quality of Life and Mortality of Long-Term Colorectal Cancer Survivors in the Seattle Colorectal Cancer Family Registry

    PubMed Central

    Adams, Scott V.; Ceballos, Rachel; Newcomb, Polly A.

    2016-01-01

    Background and Aim Because most colorectal cancer patients survive beyond five years, understanding quality of life among these long-term survivors is essential to providing comprehensive survivor care. We sought to identify personal characteristics associated with reported quality of life in colorectal cancer survivors, and sub-groups of survivors potentially vulnerable to very low quality of life. Methods We assessed quality of life using the Veterans RAND 12-item Health Survey within a population-based sample of 1,021 colorectal cancer survivors in the Seattle Colorectal Cancer Family Registry, approximately 5 years post-diagnosis. In this case-only study, mean physical component summary scores and mental component summary scores were examined with linear regression. To identify survivors with substantially reduced ability to complete daily tasks, logistic regression was used to estimate odds ratios for “very low” summary scores, defined as a score in the lowest decile of the reference US population. All cases were followed for vital status following QoL assessment, and mortality was analyzed with Cox proportional hazards regression. Results Lower mean physical component summary score was associated with older age, female sex, obesity, smoking, and diabetes or other co-morbidity; lower mean mental component summary score was associated with younger age and female sex. Higher odds of very low physical component summary score was associated with older age, obesity, less education, smoking, co-morbidities, and later stage at diagnosis; smoking was associated with higher odds of very low mental component summary score. A very low physical component score was associated with higher risk of mortality (hazard ratio (95% confidence interval): 3.97 (2.95–5.34)). Conclusions Our results suggest that identifiable sub-groups of survivors are vulnerable to very low physical components of quality of life, decrements that may represent meaningful impairment in completing

  14. Assessment of a HER2 scoring system for colorectal cancer: results from a validation study.

    PubMed

    Valtorta, Emanuele; Martino, Cosimo; Sartore-Bianchi, Andrea; Penaullt-Llorca, Frédérique; Viale, Giuseppe; Risio, Mauro; Rugge, Massimo; Grigioni, Walter; Bencardino, Katia; Lonardi, Sara; Zagonel, Vittorina; Leone, Francesco; Noe, Johannes; Ciardiello, Fortunato; Pinto, Carmine; Labianca, Roberto; Mosconi, Stefania; Graiff, Claudio; Aprile, Giuseppe; Frau, Barbara; Garufi, Carlo; Loupakis, Fotios; Racca, Patrizia; Tonini, Giuseppe; Lauricella, Calogero; Veronese, Silvio; Truini, Mauro; Siena, Salvatore; Marsoni, Silvia; Gambacorta, Marcello

    2015-11-01

    We sought to develop criteria for ERBB2-positivity (HER2) in colorectal cancer to ensure accurate identification of ERBB2-amplified metastatic colorectal cancer patients suitable for enrollment in a phase II trial of ERBB2-targeted therapy (HERACLES trial). A two-step approach was used. In step 1, a consensus panel of pathologists adapted existing protocols for use in colorectal cancer to test ERBB2 expression and amplification. Collegial revision of an archival test cohort of colorectal cancer samples led to specific recommendations for adapting current breast and gastric cancer criteria for scoring ERBB2 in colorectal cancer. In step 2, from September 2012 to January 2015, colorectal-specific ERBB2 testing protocols and ERBB2 scoring criteria were used to centrally screen for ERBB2-positive KRAS wild-type colorectal cancer patients to be enrolled in the HERACLES trial (clinical validation cohort). In both archival test (N=256) and clinical validation (N=830) cohorts, a clinically sizeable 5% fraction of KRAS wild-type colorectal cancer patients was found to be ERBB2-positive according to the colorectal cancer-specific ERBB2 scoring criteria. ERBB2-positive tumors showed ERBB2 immunostaining consisting of intense membranous ERBB2 protein expression, corresponding to homogenous ERBB2 amplification, in >50% of cells. None of the immunohistochemistry 0 or 1+ cases was amplified. Concordance between SISH and FISH was 100%. In conclusion, we propose specific criteria for defining ERBB2-positivity in colorectal cancer (HERACLES Diagnostic Criteria). In a phase II trial of trastuzumab and lapatinib in a cetuximab-resistant population, HERACLES Diagnostic Criteria shaped the selection of patients and defined ERBB2 as a predictive marker for response to ERBB2-targeted therapy in metastatic colorectal cancer. PMID:26449765

  15. 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

  16. 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

  17. Role of micro-RNA in colorectal cancer screening.

    PubMed

    Rodríguez-Montes, José Antonio; Menéndez Sánchez, Pablo

    2014-12-01

    MicroRNAs are involved in carcinogenesis through postranscriptional gene regulatory activity. These molecules are involved in various physiological and pathological functions, such as apoptosis, cell proliferation and differentiation, which indicates their functionality in carcinogenesis as tumour suppressor genes or oncogenes. Several studies have determined the presence of microRNAs in different neoplastic diseases such as colon, prostate, breast, stomach, pancreas, and lung cancer. There are promising data on the usefulness of quantifying microRNAs in different organic fluids and tissues. We have conducted a review of the determinations of microRNAs in the diagnosis of colorectal cancer. PMID:25088411

  18. 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

  19. Colonoscopy and chromoscopy in hereditary colorectal cancer syndromes.

    PubMed

    Jenkins Wessling, Erin; Lanspa, Stephen J

    2016-07-01

    With hereditary colorectal cancer prevention studies it is difficult to demonstrate reduced mortality. Large populations are needed with well characterized genetics followed over a long period of time. Those studies do exist for standard white light colonoscopy surveillance in Lynch syndrome, but not for newer technologies including chromoscopy. For these newer technologies adenoma detection rate becomes the stand-in for mortality, and the assumption is made that surveillance efficacy impacts cancer occurrence. Though well-designed and important work exists in this area, the data do not support firm conclusions regarding the use of chromoscopy in Lynch syndrome. PMID:26892866

  20. 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

  1. Endoscopy-guided orthotopic implantation of colorectal cancer cells results in metastatic colorectal cancer in mice.

    PubMed

    Bettenworth, Dominik; Mücke, Marcus M; Schwegmann, Katrin; Faust, Andreas; Poremba, Christopher; Schäfers, Michael; Domagk, Dirk; Lenz, Philipp

    2016-08-01

    Advanced stage colorectal cancer (CRC) is still associated with limited prognosis. For preclinical evaluation of novel therapeutic approaches, murine models with orthotopic tumor growth and distant metastases are required. However, these models usually require surgical procedures possibly influencing tumor immunogenicity and development. The aim of this study was to establish a minimal-invasive endoscopy-based murine orthotopic model of metastatic CRC. During colonoscopy of CD-1 nude and non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice, implantation of Caco-2 and HT-29 CRC cells was performed subcutaneously (s.c.) or orthotopic into the colonic submucosa. White light endoscopy (WLE) and fluorescence endoscopy (FE) were applied for tumor detection in vivo. Ex vivo, resected tumors were examined by fluorescence reflectance imaging (FRI), histology, gelatin zymography and immunohistochemistry. In CD-1 nude mice, marked tumor growth was observed within 14 days after subcutaneous implantation while submucosal implantation failed to induce CRC after 17 weeks. In contrast, in NOD/SCID mice submucosal injection of HT-29 cells resulted in pronounced tumor growth 12 days post injectionem. Subsequently, rapid tumor expansion occurred, occupying the entire colonic circumference. Importantly, post mortem histological analyses confirmed liver metastases in 28.6 % and peritoneal metastases in 14.3 % of all mice. FRI and gelatin zymography did not detect a significantly increased matrix metalloproteinases (MMPs) expression in s.c. implanted tumors while MMP-tracer uptake was significantly enhanced in orthotopic implanted tumors. Neither s.c. nor orthotopic Caco-2 cell implantation resulted in tumor development. We successfully established an endoscopy-based model of metastatic CRC in immunodeficient mice. PMID:27146063

  2. 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

  3. Colorectal polyps

    MedlinePlus

    ... SJ, et al. United States Multi-Society Task Force on Colorectal Cancer. Guidelines for colonoscopy surveillance after ... consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology . 2012;143:844-857. ...

  4. 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

  5. Association of health beliefs and colonoscopy use among survivors of colorectal cancer

    PubMed Central

    Salz, Talya; Brewer, Noel T.; Sandler, Robert S.; Weiner, Bryan J.; Martin, Christopher F.; Weinberger, Morris

    2009-01-01

    Objectives Clinical practice guidelines recommend ongoing testing (surveillance) for colorectal cancer survivors because they remain at risk for both local recurrences and second primary tumors. However, survivors often do not receive colorectal cancer surveillance. We used the Health Belief Model (HBM) to identify health beliefs that predict intentions to obtain routine colonoscopies among colorectal cancer survivors. Methods We completed telephone interviews with 277 colorectal cancer survivors who were diagnosed four years earlier, between 2003 and 2005, in North Carolina. The interview measured health beliefs, past preventive behaviors, and intentions to have a routine colonoscopy in the next five years. Results In bivariate analyses, most HBM constructs were associated with intentions. In multivariable analyses, greater perceived likelihood of colorectal cancer (OR=2.00, 95% CI=1.16–3.44) was associated with greater intention to have a colonoscopy. Survivors who already had a colonoscopy since diagnosis also had greater intentions of having a colonoscopy in the future (OR=9.47, 95% CI=2.08–43.16). Conclusions Perceived likelihood of colorectal cancer is an important target for further study and intervention to increase colorectal cancer surveillance among survivors. Other health beliefs were unrelated to intentions, suggesting that the health beliefs of colorectal cancer survivors and asymptomatic adults may differ due to the experience of cancer. PMID:19760152

  6. 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

  7. Integrin αvβ6 sets the stage for colorectal cancer metastasis.

    PubMed

    Cantor, D I; Cheruku, H R; Nice, E C; Baker, M S

    2015-12-01

    The β6 subunit of the αvβ6 integrin heterodimer has long been an enigma in cancer biology though recent research has provided many new insights into its biology. Collectively, these findings include discovery of the transcriptional, translational and cell biological mechanisms by which β6 acts, the identification of the cellular influences β6 exerts upon the cell proteome, the characterisation of multiple β6-centric pro-metastatic signalling systems and the search for pharmacological therapies (industry and academia) targeted against β6. Once expressional restriction is overcome in early colorectal cancer (CRC), epithelial cell surface restricted αvβ6 can physically interact with, and activate, known oncoproteins, and has the potential to enable the cross-talk through non-canonical signal transduction pathways, resulting in the adoption of an invasive/metastatic phenotype. This recent research has identified numerous interconnections and potential feedback loops, highlighting the fact that the expression of the β6 subunit may initiate a cascade of downstream effects on the CRC cell rather than acting through a single mechanism. We here review these recent studies and postulate that the existence of a cell surface uPAR/αvβ6/TGFβ "metastasome" interactome in/on a proportion of colorectal cancer cells, where β6 expression sequesters and activates multiple systems at the invasive front of tumour lesions, promoting cancer metastasis and hence explaining why β6 has been correlated with reduced patient survival in CRC. PMID:26337740

  8. Recent patents and advances in genomic biomarker discovery for colorectal cancers.

    PubMed

    Quyun, Chen; Ye, Zhiyun; Lin, Sheng-Cai; Lin, Biaoyang

    2010-06-01

    Colorectal cancer (CRC) is the third most common cancer in the world. Early diagnosis of colorectal cancer is the key to reducing the death rate of CRC patients. Predicting the response to current therapeutic modalities of CRC will also have a great impact on patient care. This review summarizes recent advances and patents in biomarker discovery in CRC under five major categories; including genomic changes, expression changes, mutations, epigenetic changes and microRNAs. The interesting patents include: 1) a patent for a method to differentiate normal exfoliated cells from cancer cells based on whether they were subjected to apoptosis and DNA degradation; 2) A model (PM-33 multiple molecular marker model) based on expression changes of up-regulation of the MDM2, DUSP6, and NFl genes down-regulation of the RNF4, MMD and EIF2S3 genes, which achieved an 88% sensitivity, and an 82% specificity for CRC diagnosis; 3) gene mutations in PTEN, KRAS, PIK3CA for predicting the response to anti-EGFR therapies, a common drug used for CRC treatment; 4) patents on epigenetic changes of ITGA4, SEPT9, ALX4, TFAP2E FOXL2, SARM1, ID4 etc. and many key miRNAs. Finally, future directions in the fields were commented on or suggested, including the combination of multiple categories of biomarkers and pathway central or network-based biomarker panels. PMID:20426761

  9. Colorectal Cancer Classification and Cell Heterogeneity: A Systems Oncology Approach

    PubMed Central

    Blanco-Calvo, Moisés; Concha, Ángel; Figueroa, Angélica; Garrido, Federico; Valladares-Ayerbes, Manuel

    2015-01-01

    Colorectal cancer is a heterogeneous disease that manifests through diverse clinical scenarios. During many years, our knowledge about the variability of colorectal tumors was limited to the histopathological analysis from which generic classifications associated with different clinical expectations are derived. However, currently we are beginning to understand that under the intense pathological and clinical variability of these tumors there underlies strong genetic and biological heterogeneity. Thus, with the increasing available information of inter-tumor and intra-tumor heterogeneity, the classical pathological approach is being displaced in favor of novel molecular classifications. In the present article, we summarize the most relevant proposals of molecular classifications obtained from the analysis of colorectal tumors using powerful high throughput techniques and devices. We also discuss the role that cancer systems biology may play in the integration and interpretation of the high amount of data generated and the challenges to be addressed in the future development of precision oncology. In addition, we review the current state of implementation of these novel tools in the pathological laboratory and in clinical practice. PMID:26084042

  10. Evaluation of ST13 gene expression in colorectal cancer patients.

    PubMed

    Dong, Qing-hua; Zheng, Shu; Hu, Yue; Chen, Gong-xing; Ding, Jia-Yi

    2005-12-01

    We identified a novel gene ST13 from a subtractive cDNA library of normal intestinal mucosa in 1993, more studies showed that ST13 was a co-chaperone of Hsp70s. Recently we detected the ST13 gene expression in tumor tissue and adjacent normal tissue of the same colorectal cancer patient and investigated if the ST13 gene expression might have any prognostic value. Analysis was performed at molecular level by reverse transcription-PCR using real-time detection method. We measured two genes simultaneously, ST13 as the target gene and glyceraldehydes-3-phosphate dehydrogenase as a reference gene, in primary colorectal tumor specimens and tumor-adjacent normal mucosa specimens from 50 colorectal cancer patients. The expression levels of the ST13 gene were significantly decreased in primary tumors compared with adjacent mucosa (P<0.05). But there were no significant differences in the expression of ST13 as compared with different Dukes' stage, tumor differentiation grade, invasion depth, lymph node metastasis and disease-specific survival. PMID:16358374

  11. 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

  12. Serum 25-hydroxyvitamin D, vitamin D binding protein and risk of colorectal cancer in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

    PubMed

    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

    2015-03-15

    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

  13. 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. |

  14. IRON AND COLORECTAL CANCER RISK IN THE ALPHA-TOCOPHEROL, BETA-CAROTENE CANCER PREVENTION STUDY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In vitro and in vivo studies have associated iron with both the initiation and promotional stages of carcinogenesis. We investigated whether iron was associated with colorectal cancer in a nested case-control study within the a-tocopherol, b-carotene cancer prevention study cohort. Exposure was asse...

  15. The Melbourne Colorectal Cancer Study: reflections on a 30-year experience.

    PubMed

    Kune, Gabriel A

    This article reflects on 30 years of conducting the Melbourne Colorectal Cancer Study, a comprehensive, population-based investigation of colorectal cancer (CRC). The study had an incidence arm, a case-control arm and a survival arm, and contributed considerable knowledge about CRC risk, aetiology, prevention and screening. The incidence arm: confirmed high rates of CRC in Australia and the prevalent view that rates rise in first-generation immigrants from countries with low rates of CRC; and enabled the first report of high rates of colon cancer among Australian Jewish people and the first report of high rectal cancer rates anywhere. The case-control arm elicited: the contribution of family history, antecedent colorectal polypectomy and multiple antecedent stressful life events to CRC risk; the risk of rectal cancer in habitual beer drinkers; the first dietary risk score (emphasising the importance of a diet pursued over adult life that is high in foods of plant origin and fish, and low in fat and red meat); and the highly protective effect of regular aspirin use (stimulating much research globally, with the possibility of aspirin becoming an important preventive agent). The survival arm: found an adjusted CRC-specific 5-year survival rate of 42% among patients with CRC and 85% among matched control subjects; confirmed cancer stage as the most important single determinant of survival; and found that the survival rate among people with the earliest stage of CRC was only marginally lower than that of matched community control subjects, underlining the importance of early detection. PMID:21143050

  16. 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

  17. Prevalence of JC Virus in Chinese Patients with Colorectal Cancer

    PubMed Central

    Mou, Xiaozhou; Chen, Ling; Liu, Fanlong; Lin, Jian; Diao, Pingping; Wang, Haohao; Li, Yifei; Lin, Jianjiang; Teng, Lisong; Xiang, Charlie

    2012-01-01

    Background JCV is a DNA polyomavirus very well adapted to humans. Although JCV DNA has been detected in colorectal cancers (CRC), the association between JCV and CRC remains controversial. In China, the presence of JCV infection in CRC patients has not been reported. Here, we investigated JCV infection and viral DNA load in Chinese CRC patients and to determine whether the JCV DNA in peripheral blood (PB) can be used as a diagnostic marker for JCV-related CRC. Methodology/Principal Findings Tumor tissues, non-cancerous tumor-adjacent tissues and PB samples were collected from 137 CRC patients. In addition, 80 normal colorectal tissue samples from patients without CRC and PB samples from 100 healthy volunteers were also harvested as controls. JCV DNA was detected by nested PCR and glass slide-based dot blotting. Viral DNA load of positive samples were determined by quantitative real-time PCR. JCV DNA was detected in 40.9% (56/137) of CRC tissues at a viral load of 49.1 to 10.3×104 copies/µg DNA. Thirty-four (24.5%) non-cancerous colorectal tissues (192.9 to 4.4×103 copies/µg DNA) and 25 (18.2%) PB samples (81.3 to 4.9×103 copies/µg DNA) from CRC patients were positive for JCV. Tumor tissues had higher levels of JCV than non-cancerous tissues (P = 0.003) or PB samples (P<0.001). No correlation between the presence of JCV and demographic or medical characteristics was observed. The JCV prevalence in PB samples was significantly associated with the JCV status in tissue samples (P<0.001). Eleven (13.8%) normal colorectal tissues and seven (7.0%) PB samples from healthy donors were positive for JCV. Conclusions/Significance JCV infection is frequently present in colorectal tumor tissues of CRC patients. Although the association between JCV presence in PB samples and JCV status in tissue samples was identified in this study, whether PB JCV detection can serve as a marker for JCV status of CRC requires further study. PMID:22606241

  18. 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

  19. 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

  20. 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

  1. FOXC2 promotes colorectal cancer metastasis by directly targeting MET.

    PubMed

    Cui, Y-M; Jiao, H-L; Ye, Y-P; Chen, C-M; Wang, J-X; Tang, N; Li, T-T; Lin, J; Qi, L; Wu, P; Wang, S-Y; He, M-R; Liang, L; Bian, X-W; Liao, W-T; Ding, Y-Q

    2015-08-13

    Metastasis is the major cause of death in colorectal cancer (CRC). Although multiple genes have been identified to be responsible for the development of CRC, the molecular changes that enable CRC cells to undergo early local invasion and to form distant metastatic colonies still remain largely unknown. Herein, we investigated the role of Forkhead box protein C2 (FOXC2) and explored the underlying mechanisms in invasion and metastasis of CRC. We show that both high FOXC2 expression and nuclear localization of FOXC2 are significantly correlated with advanced TNM (T=primary tumor; N=regional lymph nodes; M=distant metastasis) stages. FOXC2 enhanced the invasive abilities of CRC cells in vitro and promoted local invasion and distant metastasis in an orthotopic mouse metastatic model of CRC. Microarray analysis revealed that overexpression of FOXC2 increased the proto-oncogene MET tyrosine kinase expression and activated the hepatocyte growth factor (HGF)-MET signaling pathway. Furthermore, luciferase reporter assays and chromatin immunoprecipitation assays revealed that FOXC2 directly associated with MET promoter to increase the transcriptional activity of MET. Inhibition of MET attenuates the invasive phenotype and metastatic potential of FOXC2-overexpressing CRC cells, indicating that MET is a major mediator of FOXC2-promoted metastasis. In addition, FOXC2 expression was positively correlated with MET expression in CRC tissue samples. Our findings suggest that FOXC2 has a crucial role in CRC metastasis by regulating HGF-MET signaling via inducing MET expression, highlighting FOXC2 as a potential therapeutic target for preventing or reducing metastasis in CRC. PMID:25381815

  2. 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

  3. 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

  4. [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

  5. 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…

  6. Targeting Six1 by lentivirus-mediated RNA interference inhibits colorectal cancer cell growth and invasion

    PubMed Central

    Li, Zhaoming; Tian, Tian; Hu, Xiaopeng; Zhang, Xudong; Li, Lifeng; Nan, Feifei; Chang, Yu; Wang, Xinhua; Sun, Zhenchang; Lv, Feng; Zhang, Mingzhi

    2014-01-01

    The Six1 homeodomain protein is a developmental transcription factor that has been implicated in tumor onset and progression. Recently, it’s reported that overexpression of Six1 is sufficient to induce epithelial-to-mesenchymal transition (EMT) and metastasis of colorectal cancer. Moreover, its expression is significantly associated with poorer overall survival probability in advanced-stage colorectal cancer. To address whether Six1 could serve as a therapeutic target for human colorectal cancer, we used a lentivirus-mediated short hairpin RNA (shRNA) gene knockdown method to suppress the expression of Six1 in colorectal cancer cells. We showed that lentivirusmediated shRNA targeted to Six1 gene efficiently reduced its expression in colorectal cancer cells at both mRNA and protein levels. In vitro functional assays revealed that knockdown of Six1 significantly suppressed cell proliferation, and inhibited cell migration and invasion of colorectal cancer cells. Furthermore, tumor xenograft model demonstrated that downregulation of Six1 dramatically inhibited colorectal cancer growth in vivo. In conclusion, these findings suggest that lentivirus-mediated Six1 inhibition may represent a novel therapeutic approach for treatment of colorectal cancer. PMID:24551283

  7. A PROSPECTIVE STUDY OF SERUM C-REACTIVE PROTEIN AND COLORECTAL CANCER RISK IN MEN

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chronic inflammation has been implicated in the etiology of colorectal cancer. C-reactive protein (CRP), a sensitive marker of inflammation, has been investigated with regard to colorectal cancer in only three previous studies and results from these investigations are inconsistent. We examined ser...

  8. 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...

  9. Clinical and therapeutic significance of sirtuin-4 expression in colorectal cancer.

    PubMed

    Huang, Guoyu; Cheng, Jun; Yu, Fudong; Liu, Xisheng; Yuan, Chenwei; Liu, Chenchen; Chen, Xiaolei; Peng, Zhihai

    2016-05-01

    Several members of the sirtuin family (SIRT1-7), which are a highly conserved family of NAD+-dependent enzymes, play an important role in tumor formation. Recent studies indicate that SIRT4 acts as a tumor suppressor by regulating glutamine metabolism. In the present study, we investigated the expression and activity of SIRT4 in colorectal cancer. Using a tissue microarray of 89 colorectal cancer cases, we found that SIRT4 was significantly downregulated in colorectal cancer tissues compared with that noted in the corresponding normal tissue (P<0.001). Lower SIRT4 levels were associated with worse pathological differentiation (P=0.031) and poorer post-operative overall survival rate (P=0.041). We found that SIRT4 overexpression inhibited the proliferation of colorectal cancer cells in vitro and in vivo. SIRT4 inhibited the glutamine metabolism of colorectal cancer cells and synergistically with glycolysis inhibitors induced cell death. SIRT4 also increased the sensitivity of colorectal cancer cells to chemotherapeutic drug 5-fluorouracil by inhibiting the cell cycle. Together, these results highlight the prognostic value of SIRT4 in colorectal cancer and the potential application of SIRT4 in colorectal cancer treatment. PMID:26986234

  10. 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

  11. [Correlation between microsatellite instability and morphology in colorectal cancer].

    PubMed

    Szentirmay, Zoltán; Gallai, Mónika; Serester, Orsolya; Szoke, János; Tóth, Erika

    2010-06-01

    Microsatellite instability (MSI) influences the development and clinical course of colorectal cancers (CRCs) and induce specific morphological alterations of such neoplasms, therefore hematoxylin-eosin (H&E) based histology allows to predict the microsatellite status of a given tumor. The aim of this article is to demonstrate clinicopathological features that are useful in recognition of microsatellite-stable and -unstable CRCs on routine histological examination. In the Center of Surgical and Molecular Pathology of National Institute of Oncology, from 384 CRC cases 26 hereditary non-polyposis colorectal cancers (HNPCC), 22 sporadic high-level microsatellite-instable (MSI-H) cancers and 76 microsatellite-stable (MSS) or low-level MSI (MSI-L) CRCs were selected on the basis of the localization, clinical stage, microsatellite status, and patient age at the time of the diagnosis. Our results showed that we can recognize MSS/MSI-L carcinomas, HNPCCs and sporadic MSI-H tumors with high probability on the base of clinicopathological features like patient's age, tumor localization, clinical stage and histological characteristics of CRCs, even if the genetic MSI test is not available. The main morphological characteristics related to microsatellite instability are intratumoral or stromal infiltrating lymphocytes/leukocytes, large, vesicular nuclei with prominent nucleoli, and expansive infiltrative edge of the tumors. Careful and detailed morphological analysis of colorectal cancers helps to select the appropriate molecular method to determine the molecular features that influence the clinical care of patients and allow to consider the most appropriate anti-tumor therapy. PMID:20576594

  12. Identification and characterization of colorectal cancer using Raman spectroscopy and feature selection techniques.

    PubMed

    Li, Shaoxin; Chen, Gong; Zhang, Yanjiao; Guo, Zhouyi; Liu, Zhiming; Xu, Junfa; Li, Xueqiang; Lin, Lin

    2014-10-20

    This study aims to detect colorectal cancer with near-infrared Raman spectroscopy and feature selection techniques. A total of 306 Raman spectra of colorectal cancer tissues and normal tissues are acquired from 44 colorectal cancer patients. Five diagnostically important Raman bands in the regions of 815-830, 935-945, 1131-1141, 1447-1457 and 1665-1675 cm(-1) related to proteins, nucleic acids and lipids of tissues are identified with the ant colony optimization (ACO) and support vector machine (SVM). The diagnostic models built with the identified Raman bands provide a diagnostic accuracy of 93.2% for identifying colorectal cancer from normal Raman spectroscopy. The study demonstrates that the Raman spectroscopy associated with ACO-SVM diagnostic algorithms has great potential to characterize and diagnose colorectal cancer. PMID:25401621

  13. Targeting cancer testis antigens for biomarkers and immunotherapy in colorectal cancer: Current status and challenges

    PubMed Central

    Suri, Anil; Jagadish, Nirmala; Saini, Shikha; Gupta, Namita

    2015-01-01

    Colorectal cancer ranks third among the estimated cancer cases and cancer related mortalities in United States in 2014. Early detection and efficient therapy remains a significant clinical challenge for this disease. Therefore, there is a need to identify novel tumor associated molecules to target for biomarker development and immunotherapy. In this regard, cancer testis antigens have emerged as a potential targets for developing novel clinical biomarkers and immunotherapy for various malignancies. These germ cell specific proteins exhibit aberrant expression in cancer cells and contribute in tumorigenesis. Owing to their unique expression profile and immunogenicity in cancer patients, cancer testis antigens are clinically referred as the most promising tumor associated antigens. Several cancer testis antigens have been studied in colorectal cancer but none of them could be used in clinical practice. This review is an attempt to address the promising cancer testis antigens in colorectal cancer and their possible clinical implications as biomarkers and immunotherapeutic targets with particular focus on challenges and future interventions. PMID:26691579

  14. 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

  15. Advances in epigenetic biomarker research in colorectal cancer

    PubMed Central

    Wang, Xi; Kuang, Ye-Ye; Hu, Xiao-Tong

    2014-01-01

    Colorectal cancer (CRC) causes approximately 600000 deaths annually and is the third leading cause of cancer mortality worldwide. Despite significant advancements in treatment options, CRC patient survival is still poor owing to a lack of effective tools for early diagnosis and a limited capacity for optimal therapeutic decision making. Since there exists a need to find new biomarkers to improve diagnosis of CRC, the research on epigenetic biomarkers for molecular diagnostics encourages the translation of this field from the bench to clinical practice. Epigenetic alterations are thought to hold great promise as tumor biomarkers. In this review, we will primarily focus on recent advances in the study of epigenetic biomarkers for colorectal cancer and discuss epigenetic biomarkers, including DNA methylation, microRNA expression and histone modification, in cancer tissue, stool, plasma, serum, cell lines and xenografts. These studies have improved the chances that epigenetic biomarkers will find a place in the clinical practices of screening, early diagnosis, prognosis, therapy choice and recurrence surveillance for CRC patients. However, these studies have typically been small in size, and evaluation at a larger scale of well-controlled randomized clinical trials is the next step that is necessary to increase the quality of epigenetic biomarkers and ensure their widespread clinical use. PMID:24764665

  16. 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

  17. Prognostic significance of INF-induced transmembrane protein 1 in colorectal cancer

    PubMed Central

    He, Jingdong; Li, Jin; Feng, Wanting; Chen, Longbang; Yang, Kangqun

    2015-01-01

    Interferon-induced transmembrane protein 1 (IFITM1) has recently been implicated in tumorigenesis. However, the prognostic value of IFITM1 in colorectal cancer remains unknown. The present study aimed to examine the expression and prognostic significance of IFITM1 in human colorectal cancer. IFITM1 expression was analyzed in 144 archived, paraffin-embedded colorectal cancer tissues and corresponding normal colorectal mucosa by immunohistochemistry. The correlation of IFITM1 with clinic-pathological features and overall survival of colorectal cancer patients was evaluated. IFITM1 was overexpressed in colonic cancer tissues but not in rectal cancer tissues, compared to control normal tissues. The expression of IFITM1 was significantly higher in patients with poor differentiation (P=0.031). The patients with higher IFITM1 expression had worse overall survival outcomes than those with lower IFITM1 expression in rectal cancer (P=0.037). Univariate Cox regression suggested that older age and poorly differentiation status predict shorter overall survival in colorectal cancer (P<0.05). However, IFITM1 expression was not a significant prognostic factor for survival by univariate or multivariate analyses. In conclusion, high expression of IFITM1 is associated with poor prognosis of rectal cancer. IFITM1 may serve as an independent prognostic biomarker for colorectal cancer. PMID:26884876

  18. Targeting cell death signaling in colorectal cancer: Current strategies and future perspectives

    PubMed Central

    Koehler, Bruno Christian; Jäger, Dirk; Schulze-Bergkamen, Henning

    2014-01-01

    The evasion from controlled cell death induction has been considered as one of the hallmarks of cancer cells. Defects in cell death signaling are a fundamental phenomenon in colorectal cancer. Nearly any non-invasive cancer treatment finally aims to induce cell death. However, apoptosis resistance is the major cause for insufficient therapeutic success and disease relapse in gastrointestinal oncology. Various compounds have been developed and evaluated with the aim to meet with this obstacle by triggering cell death in cancer cells. The aim of this review is to illustrate current approaches and future directions in targeting cell death signaling in colorectal cancer. The complex signaling network of apoptosis will be demonstrated and the “druggability” of targets will be identified. In detail, proteins regulating mitochondrial cell death in colorectal cancer, such as Bcl-2 and survivin, will be discussed with respect to potential therapeutic exploitation. Death receptor signaling and targeting in colorectal cancer will be outlined. Encouraging clinical trials including cell death based targeted therapies for colorectal cancer are under way and will be demonstrated. Our conceptual understanding of cell death in cancer is rapidly emerging and new types of controlled cellular death have been identified. To meet this progress in cell death research, the implication of autophagy and necroptosis for colorectal carcinogenesis and therapeutic approaches will also be depicted. The main focus of this topic highlight will be on the revelation of the complex cell death concepts in colorectal cancer and the bridging from basic research to clinical use. PMID:24587670

  19. Colorectal Cancer: What You Should Know

    MedlinePlus

    ... Devices Radiation-Emitting Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products For Consumers Home For Consumers ... Online Cancer Fraud More in Consumer Updates Animal & Veterinary Children's Health Cosmetics Dietary Supplements Drugs Food Medical ...

  20. 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

  1. Retrospective analysis of KRAS status in metastatic colorectal cancer patients: a single-center feasibility study

    PubMed Central

    Montomoli, Jonathan; Hamilton-Dutoit, Stephen Jacques; Frøslev, Trine; Taylor, Aliki; Erichsen, Rune

    2012-01-01

    Background: The occurrence of KRAS mutations and their association with prognosis in metastatic colorectal cancer patients is not well documented in population-based studies. Objectives: To examine the feasibility of identifying archived colorectal cancer specimens, and through linkage with nationwide Danish population-based databases to investigate the prevalence of KRAS mutations and their association with colorectal cancer survival. Methods: We used the Danish Pathology Database to identify the physical location of primary (or in some cases secondary) tumor specimens from selected metastatic colorectal cancer patients referred to our hospital for palliative chemotherapy between November 1, 2008 and September 30, 2009. Routinely stored paraffin tissue blocks were obtained from the pathology archives of the originating hospital. KRAS mutation tumor status was assessed for each patient using the commercialized TheraScreen KRAS Mutation Kit. Using the unique identifier number, we linked the patients to the Danish National Registry of Patients and the Danish Civil Registration System to obtain data on date of first colorectal cancer diagnosis and follow-up status. We estimated prevalence of KRAS mutations and the 1-, 2-, and 5-year survival after colorectal cancer diagnosis using the Kaplan–Meier technique. Results: We identified 106 metastatic colorectal cancer patients (64% males). All were successfully linked to the registries, and archived tumor-tissue samples were obtained and analyzed in each case. The overall prevalence of KRAS mutations was 55%, and 1-, 2-, and 5-year overall survival after colorectal cancer diagnosis was 91%, 68%, and 25%, respectively. Conclusion: It is feasible to use Danish population-based registries to obtain archived tissue samples from metastatic colorectal cancer patients, and to estimate prevalence of KRAS mutation and subsequently evaluate the association with colorectal cancer survival. PMID:23028236

  2. 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

  3. A decision analysis of surveillance for colorectal cancer in ulcerative colitis

    PubMed Central

    Delco, F; Sonnenberg, A

    2000-01-01

    BACKGROUND—Patients with long standing, extensive ulcerative colitis have an increased risk of developing colorectal cancer.
AIMS—To assess the feasibility of surveillance colonoscopy in preventing death from colorectal cancer.
PATIENTS—A hypothetical cohort of patients with chronic ulcerative colitis.
METHODS—The benefits of life years saved were weighted against the costs of biannual colonoscopy and proctocolectomy, and the terminal care of patients dying from colorectal cancer. Two separate Markov processes were modelled to compare the cost-benefit relation in patients with or without surveillance. The cumulative probability of developing colorectal cancer served as a threshold to determine which of the two management strategies is associated with a larger net benefit.
RESULTS—If the cumulative probability of colorectal cancer exceeds a threshold value of 27%, surveillance becomes more beneficial than no surveillance. The threshold is only slightly smaller than the actual cumulative cancer rate of 30%. Variations of the assumptions built into the model can raise the threshold above or lower it far below the actual rate. If several of the assumptions are varied jointly, even small changes can lead to extreme threshold values.
CONCLUSIONS—It is not possible to prove that frequent colonoscopies scheduled at regular intervals are an effective means to manage the increased risk of colorectal cancer associated with ulcerative colitis.


Keywords: cancer screening; colorectal cancer; health economics; medical decision analysis; surveillance colonoscopy; ulcerative colitis PMID:10716679

  4. GSTM1 polymorphism contribute to colorectal cancer in Asian populations: a prospective meta-analysis

    PubMed Central

    Li, Jing; Xu, Wen; Liu, Fang; Huang, Silin; He, Meirong

    2015-01-01

    Glutathione S-transferases (GSTs) are enzymes which expressed in many tissues and play important roles in neutralization of toxic compounds, and protecting hosts against cancer. Among several GSTs, Glutathione S-transferases mu (GSTM) has been drawn attention upon the association with the genetic risk for many types of cancers. But whether the GSTM1 polymorphisms confer the susceptibility to colorectal cancer in Asians has not been well established. We searched the PubMed database with GSTM1, polymorphism and colorectal cancer, attempting to identify the eligible studies. In total, 33 case-control studies in Asian populations with 8502 colorectal cancer patients and 13699 controls were included in the current meta-analysis. The association between the polymorphism and susceptibility to colorectal cancer was evaluated by the odds ratio (OR) and 95% confidence intervals (CI). The pooled meta-analysis suggested that GSTM1 null variant was correlated to the colorectal cancer risk in Asians. There was a marginal heterogeneity among these eligible studies. Nevertheless, cumulative meta-analysis observed a trend of an obvious association between the GSTM1 null genotype and colorectal cancer risk in Asians. In summary, the meta-analysis suggested that GSTM1 null polymorphism confer the susceptibility to colorectal cancer in Asians, especially in Chinese populations. PMID:26219826

  5. 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

  6. Somatic gene copy number alterations in colorectal cancer: new quest for cancer drivers and biomarkers.

    PubMed

    Wang, H; Liang, L; Fang, J-Y; Xu, J

    2016-04-21

    Colorectal cancer (CRC) results from the accumulation of genetic alterations, and somatic copy number alterations (CNAs) are crucial for the development of CRC. Genome-wide survey of CNAs provides opportunities for identifying cancer driver genes in an unbiased manner. The detection of aberrant CNAs may provide novel markers for the early diagnosis and personalized treatment of CRC. A major challenge in array-based profiling of CNAs is to distinguish the alterations that play causative roles from the random alterations that accumulate during colorectal carcinogenesis. In this view, we systematically discuss the frequent CNAs in CRC, focusing on functional genes that have potential diagnostic, prognostic and therapeutic significance. PMID:26257062

  7. Gender and race/ethnicity affect the cost-effectiveness of colorectal cancer screening.

    PubMed Central

    Theuer, Charles P.; Taylor, Thomas H.; Brewster, Wendy R.; Anton-Culver, Hoda

    2006-01-01

    BACKGROUND AND AIMS: Colorectal cancer screening beginning at age 50 is recommended for all Americans considered at average risk for the development of colorectal cancer regardless of gender or race/ethnicity. We determined the influence of gender and race/ethnicity on the cost-effectiveness of recommended colorectal cancer screening regimens. METHODS: We determined age-specific colorectal cancer incidence rates; the proportion of left-sided cancers; and the proportion of localized cancers in Asian, black, Latino and white men and women using the California Cancer Registry. We incorporated these data and available data for life expectancy and colorectal cancer survival to model the cost-effectiveness of two 35-year colorectal cancer-screening interventions. RESULTS: Age-specific colorectal cancer incidence rates were highest in black men and lowest in Latino women. Screening beginning at age 50 was most cost-effective in black men and least cost-effective in Latino women (measured as dollars spent per year of life saved) using annual fecal occult blood testing combined with flexible sigmoidoscopy every five years and using colonoscopy every 10 years. The cost-effectiveness of a 35-year screening program in black men beginning at age 45 was similar to the cost-effectiveness of screening white men and black women beginning at age 50 and more cost-effective than screening nonblack women as well as Asian and Latino men beginning at age 50. CONCLUSIONS: Screening is most cost-effective in black men because of high age-specific colorectal cancer incidence rates. Initiation of colorectal cancer screening in this high-risk group prior to age 50 should be strongly considered. PMID:16532978

  8. 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

  9. 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

  10. Accumulation of arachidonic acid-containing phosphatidylinositol at the outer edge of colorectal cancer.

    PubMed

    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

  11. 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

  12. 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

  13. Efficacy of Dose-Escalated Radiotherapy for Recurrent Colorectal Cancer

    PubMed Central

    Jo, Sunmi; Park, Sung-Kwang; Kim, Jin-Young; Kim, Hyun Jung; Lee, Yun-Han; Oh, Won Yong; Cho, Heunglae; Ahn, Ki Jung

    2016-01-01

    Purpose This study aimed to evaluate the effects of radiotherapy (RT) on progression-free survival (PFS) for patients with recurrent colorectal cancer. Methods We reviewed the records of 22 patients with recurrent colorectal cancer treated with RT between 2008 and 2014. The median radiation dose for recurrent disease was 57.6 Gy (range, 45–75.6 Gy). Patients were divided into 2 groups according to the type of RT: patients underwent RT without previous history of irradiation (n = 14) and those treated with secondary RT (reirradiation: n = 8) at the time of recurrence. Results The median follow-up period was 24.9 months (range, 4.5–66.6 months). Progression was observed in 14 patients (including 8 with loco-regional failure and 9 with distant metastases). Distant metastases were related to the RT dose (<70 Gy, P = 0.031). The 2-year loco-regional control (LRC), PFS, and overall survival (OS) rates were 74.6%, 45.1%, and 82.0%, respectively. The LRC rate was not different between the patients treated with RT for the first time and those treated with reirradiation (P = 0.101, 2-year LRC 79.5% vs. 41.7%). However, reirradiation was related to poor PFS (P = 0.022) and OS (P = 0.002). An escalated RT dose (≥70 Gy) was associated with a higher PFS (P = 0.014, 2-year PFS 63.5% vs. 20.8%). Conclusion Salvage RT for locally recurrent colorectal cancer can be offered when surgery is impossible. Dose-escalated RT shows a possible benefit in reducing the risk of progression. PMID:27218097

  14. 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

  15. 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

  16. 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

  17. Obesity and Obese-related Chronic Low-grade Inflammation in Promotion of Colorectal Cancer Development.

    PubMed

    Pietrzyk, Lukasz; Torres, Anna; Maciejewski, Ryszard; Torres, Kamil

    2015-01-01

    Colorectal cancer (CRC) is a worldwide health problem, being the third most commonly detected cancer in males and the second in females. Rising CRC incidence trends are mainly regarded as a part of the rapid 'Westernization' of life-style and are associated with calorically excessive high-fat/low-fibre diet, consumption of refined products, lack of physical activity, and obesity. Most recent epidemiological and clinical investigations have consistently evidenced a significant relationship between obesity-driven inflammation in particular steps of colorectal cancer development, including initiation, promotion, progression, and metastasis. Inflammation in obesity occurs by several mechanisms. Roles of imbalanced metabolism (MetS), distinct immune cells, cytokines, and other immune mediators have been suggested in the inflammatory processes. Critical mechanisms are accounted to proinflammatory cytokines (e.g. IL-1, IL-6, IL-8) and tumor necrosis factor-α (TNF-α). These molecules are secreted by macrophages and are considered as major agents in the transition between acute and chronic inflammation and inflammation-related CRC. The second factor promoting the CRC development in obese individuals is altered adipokine concentrations (leptin and adiponectin). The role of leptin and adiponectin in cancer cell proliferation, invasion, and metastasis is attributable to the activation of several signal transduction pathways (JAK/STAT, mitogen-activated protein kinase (MAPK), phosphatidylinositol 3 kinase (PI3K), mTOR, and 5'AMPK signaling pathways) and multiple dysregulation (COX-2 downregulation, mRNA expression). PMID:26028066

  18. Molecular therapy of colorectal cancer: progress and future directions.

    PubMed

    Weng, Wenhao; Feng, Junlan; Qin, Huanlong; Ma, Yanlei

    2015-02-01

    Colorectal cancer (CRC) remains one of the most common types of cancer and leading causes of cancer death worldwide. Although the introduction of cytotoxic drugs such as oxaliplatin, irinotecan and fluorouracil has improved the treatment of advanced CRC, the individual response to chemoradiotherapy varies tremendously from one patient to another. However, recent progress in CRC molecular therapies may provide new insight into the treatment of this disease. Currently, components of the EGFR, VEGF, Wnt and NF-kB pathways are the most important targets for CRC therapy. This review chronicles the development of molecular CRC therapies over the past few decades. We also provide an update on the current progress of research concerning the molecular pathways leading to CRC and discuss the possible implications for CRC therapy. PMID:24420815

  19. mTOR pathway in colorectal cancer: an update

    PubMed Central

    Francipane, Maria Giovanna; Lagasse, Eric

    2014-01-01

    The mammalian target of rapamycin (mTOR) has emerged as a potential target for drug development, particularly due to the fact that it plays such a crucial role in cancer biology. In addition, next-generation mTOR inhibitors have become available, marking an exciting new phase in mTOR-based therapy. However, the verdict on their therapeutic efectiveness remains unclear. Here we review phosphatidylinositol-3-kinase (PI3K)/Akt/mTOR signaling as one of the primary mechanisms for sustaining tumor outgrowth and metastasis, recent advances in the development of mTOR inhibitors, and current studies addressing mTOR activation/inhibition in colorectal cancer (CRC). We will also discuss our recent comparative study of diferent mTOR inhibitors in a population of colon cancer stem cells (CSCs), and current major challenges for achieving individualized drug therapy using kinase inhibitors. PMID:24393708

  20. 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

  1. Differentially expressed microRNAs in colorectal cancer metastasis.

    PubMed

    Abba, Mohammed; Benner, Axel; Patil, Nitin; Heil, Oliver; Allgayer, Heike

    2015-12-01

    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

  2. BRD4 inhibitor inhibits colorectal cancer growth and metastasis.

    PubMed

    Hu, Yuan; Zhou, Jieqiong; Ye, Fei; Xiong, Huabao; Peng, Liang; Zheng, Zihan; Xu, Feihong; Cui, Miao; Wei, Chengguo; Wang, Xinying; Wang, Zhongqiu; Zhu, Hongfa; Lee, Peng; Zhou, Mingming; Jiang, Bo; Zhang, David Y

    2015-01-01

    Post-translational modifications have been identified to be of great importance in cancers and lysine acetylation, which can attract the multifunctional transcription factor BRD4, has been identified as a potential therapeutic target. In this paper, we identify that BRD4 has an important role in colorectal cancer; and that its inhibition substantially wipes out tumor cells. Treatment with inhibitor MS417 potently affects cancer cells, although such effects were not always outright necrosis or apoptosis. We report that BRD4 inhibition also limits distal metastasis by regulating several key proteins in the progression of epithelial-to-mesenchymal transition (EMT). This effect of BRD4 inhibitor is demonstrated via liver metastasis in animal model as well as migration and invasion experiments in vitro. Together, our results demonstrate a new application of BRD4 inhibitor that may be of clinical use by virtue of its ability to limit metastasis while also being tumorcidal. PMID:25603177

  3. 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

  4. 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. PMID:26041752

  5. Mass Spectrometry-Based N-Glycomics of Colorectal Cancer.

    PubMed

    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. Integrating anti-EGFR therapies in metastatic colorectal cancer

    PubMed Central

    Haraldsdottir, Sigurdis

    2013-01-01

    Colorectal cancer remains one of the most common causes of cancer diagnoses and mortality in the United States. The treatment of metastatic colorectal cancer has evolved significantly over the last decade with near-tripling of patient survival rate. A significant contribution to this outcome was the advent of novel targeted agents, such as the epidermal growth factor (EGFR) inhibitors. In an era of emphasis on refining therapy, the presence of KRAS mutation will predict for resistance and limit exposure to patients who are more likely to benefit. In contrast, the presence of BRAF mutations does not seem to have a predictive value. Agents that are thought to reverse resistance to EGFR inhibitors such as those targeting PI3K, c-MET or IGF-1R are currently under study. EGFR inhibitors have exhibited single agent activity, and seem to synergize very well with standard chemotherapy except for cetuximab and 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX). Preliminary data suggests that EGFR inhibitors have similar effectiveness to vascular endothelial growth factor (VEGF) inhibitors in the first line setting. Skin toxicity remains the main limiting factor for the utilization of EGFR inhibitors, but strategies including the use of agents such as minocycline or doxycycline added to topical care seem to limit the severity of the rash. PMID:23997940

  7. 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.

  8. History and present status of pulmonary metastasectomy in colorectal cancer.

    PubMed

    Treasure, Tom; Milošević, Mišel; Fiorentino, Francesca; Pfannschmidt, Joachim

    2014-10-28

    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

  9. Peptides in common bean fractions inhibit human colorectal cancer cells.

    PubMed

    Luna Vital, Diego A; González de Mejía, Elvira; Dia, Vermont P; Loarca-Piña, Guadalupe

    2014-08-15

    The aim of this study was to characterize peptides present in common bean non-digestible fractions (NDF) produced after enzymatic digestion and determine their antiproliferative action on human colorectal cancer cells. Five NDF peptides represented 70% of total protein (GLTSK, LSGNK, GEGSGA, MPACGSS and MTEEY) with antiproliferative activity on human colon cancer cells. Based on the antiproliferative effect, HCT116 cell line was most sensitive to bean Azufrado Higuera (IC50=0.53 mg/ml) and RKO to Bayo Madero (IC50=0.51 mg/ml) peptide extracts. Both cultivars increased significantly (p<0.05) the expression of p53 in HCT116 by 76% and 68%, respectively. Azufrado Higuera modified the expression of cell cycle regulation proteins p21 and cyclin B1. Bayo Madero modified the expression of mitochondrial activated apoptotic proteins BAD, cytC, c-casp3, Survivin, BIRC7. Results suggest that peptides present in common bean NDF contributed to the antiproliferative effect on human colorectal cancer cells by modifying molecules involved in either cell cycle arrest or apoptosis. PMID:24679790

  10. 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

  11. Personalizing medicine for metastatic colorectal cancer: Current developments

    PubMed Central

    Marques, Andrea Marin; Turner, Alice; de Mello, Ramon Andrade

    2014-01-01

    Metastatic colorectal cancer (mCRC) is still one of the tumor types with the highest incidence and mortality. In 2012, colorectal cancer was the second most prevalence cancer among males (9%) and the third among females (8%). In this disease, early diagnosis is important to improve treatment outcomes. However, at the time of diagnosis, about one quarter of patients already have metastases, and overall survival of these patients at 5-years survival is very low. Because of these poor statistics, the development of new drugs against specific targets, including the pathway of angiogenesis, has witnessed a remarkable increase. So, targets therapies through epidermal growth factor and its receptor and also KRAS pathways modulation acquired a main role whether in association with standard chemotherapy and radiotherapy. With the current knowledge in the field of molecular biology, including genetic mutations and polymorphisms, we know better why patients respond so differently to the same treatments. So, in the future we can develop increasingly personalized treatments to the patient and not the disease. This review aims to summarize some molecular pathways and their relation to tumor growth, as well as novel targeted developing drugs and recently approved for mCRC. PMID:25132758

  12. Netrin-4 delays colorectal cancer carcinomatosis by inhibiting tumor angiogenesis.

    PubMed

    Eveno, Clarisse; Broqueres-You, Dong; Feron, Jean-Guillaume; Rampanou, Aurore; Tijeras-Raballand, Annemilaï; Ropert, Stanislas; Leconte, Laurence; Levy, Bernard I; Pocard, Marc

    2011-04-01

    A close relationship between tumor angiogenesis, growth, and carcinomatosis has been observed. Netrin-4 (NT-4) has been shown to regulate angiogenic responses. We aimed to examine the effects of NT-4 on colon tumor angiogenesis, growth, and carcinomatosis. We showed that NT-4 was expressed in human colon cancer cells (LS174). A 20-fold increase in NT-4 expression was stably induced by NT-4 pcDNA in LS174 cells. In vivo, a Matrigel angiogenesis assay showed that NT-4 overexpression altered vascular endothelial growth factor (VEGF)/basic fibroblast growth factor-induced angiogenesis. In nude mice with LS174 xenografts, NT-4 overexpression inhibited tumor angiogenesis and growth. In addition, these NT-4-involved inhibitory effects were associated with decreased tumor cell proliferation and increased tumor cell apoptosis. Using an orthotopic peritoneal carcinomatosis model, we demonstrated that NT-4 overexpression decreased colorectal cancer carcinomatosis. Moreover, carcinomatosis-related ascites formation was significantly decreased in mice transplanted with NT-4 LS174 cells versus control LS174 cells. The antiangiogenic activity of NT-4 was probably mediated by binding to its receptor neogenin. Netrin-4 had a direct effect on neither in vitro apoptosis and proliferation of cultured LS174 cells nor the VEGF-induced acute increase in vascular permeability in vivo. We propose that NT-4 overexpression decreases tumor growth and carcinomatosis, probably via an antiangiogenic effect, underlying the potential therapeutic interest in NT-4 in the treatment of colorectal cancer growth and carcinomatosis. PMID:21406174

  13. [Recent Advances in Systemic Chemotherapy for Metastatic Colorectal Cancer].

    PubMed

    Miyamoto, Yuji; Oki, Eiji; Saeki, Hiroshi; Maehara, Yoshihiko; Baba, Hideo

    2016-01-01

    The recent development of chemotherapeutic agents and biomarkers have remarkably improved treatment outcomes of metastatic colorectal cancer (mCRC). However, decision making regarding the choice of therapy for mCRC has been complicated by the availability of many different treatment options. In this review, we will discuss the clinical evidence for current systemic treatment, including the key roles of 3 cytotoxic drugs and oral fluoropyrimidines, the appropriate use of anti-VEGF and anti-EGFR therapy, the significance of RAS mutation status as a predictive marker for anti-EGFR therapy, and new agents for salvage therapy (regorafenib and TAS-102 [TFTD]). PMID:26809522

  14. New therapeutic strategies for BRAF mutant colorectal cancers

    PubMed Central

    2015-01-01

    Oncogenic BRAF mutations are found in ~10% of colorectal cancers (CRCs) and predict poor prognosis. Although BRAF inhibitors have demonstrated striking efficacy in BRAF mutant melanomas, BRAF inhibitor monotherapy is ineffective in BRAF mutant CRC. Over the past few years, studies have begun to define the molecular mechanisms underlying the relative resistance of BRAF mutant CRC to BRAF inhibitors, leading to the development of novel therapeutic strategies that are showing promising clinical activity in initial clinical trials. Our current understanding of the mechanisms of BRAF inhibitor resistance in BRAF mutant CRC and the therapeutic approaches currently in clinical trials for BRAF mutant CRC are reviewed herein. PMID:26697198

  15. Familial colorectal cancer syndromes: an overview of clinical management.

    PubMed

    Sammour, Tarik; Hayes, Ian P; Hill, Andrew G; Macrae, Finlay A; Winter, Des C

    2015-06-01

    Familial colorectal cancer syndromes pose a complex challenge to the treating clinician. Once a syndrome is recognized, genetic testing is often required to confirm the clinical suspicion. Management from that point is usually based on disease-specific guideline recommendations targeting risk reduction for the patient and their relatives through surgery, surveillance and chemoprophylaxis. The aim of this paper is to provide an up-to-date summary of the most common familial syndromes and their medical and surgical management, with specific emphasis on evidence-based interventions that improve patient outcome, and to present the information in a manner that is easily readable and clinically relevant to the treating clinician. PMID:25779305

  16. 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

  17. Colorectal Cancer: Conversation with Katie Couric

    MedlinePlus

    ... broadcast fundraising special. We want to make every American aware that they can make a difference in this fight by helping these scientists. Whatever one individual can do in these tough economic times, every contribution—of any size—helps. The first "Dream Teams" funded by Stand Up To Cancer will ...

  18. Simultaneous radical cystectomy and colorectal cancer resection for synchronous muscle invasive bladder cancer and cT3 colorectal cancer: Our initial experience in five patients

    PubMed Central

    Liu, Zhuo; Chen, Guiping; Zhu, Yuping; Li, Dechuan

    2014-01-01

    To review cases of simultaneous radical cystectomy and colorectal cancer (CRC) resection for synchronous carcinoma of bladder and colorectum. Between May 1997 and September 2010, five patients were diagnosed with synchronous bladder cancer and CRCs. The primary colorectal tumors included three sigmoid cancers, one ascending colon cancer and one rectal cancer. All patients underwent simultaneous radical cystectomy and CRC resection. Pathologic types were confirmed by the biopsies of cystoscopy and colonoscopy. All patients were performed synchronous radical cystectomy and CRC resection. Four of them received adjuvant chemotherapies for CRC. Two of them died of liver metastasis 32.8 months and 13 months after surgery. Although patients with synchronous carcinoma of bladder and colorectum are rare, the Urologist should be alerted to this possibility when evaluating patients for the initially presenting symptoms and/or detected tumors. The simultaneous surgery is technically feasible for the selected patients. PMID:25538788

  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. Should all colorectal cancer patients over age 60 be screened for prostate cancer?

    PubMed

    Aizer, Ayal A; D'Amico, Anthony V

    2013-10-01

    Two large, randomized studies have demonstrated a prostate cancer-specific survival benefit to prostate cancer screening using the prostate-specific antigen (PSA) assay. Yet, the US Preventive Services Task Force recently recommended against PSA-based screening for prostate cancer, claiming it results in more harm than good, given concerns regarding overtreatment. The purpose of this article is to characterize the patients with colorectal cancer who are most likely to benefit from PSA-based screening for prostate cancer. Because the survival benefit due to PSA-based screening does not manifest until 7 years after screening is initiated, we conclude that PSA screening is most appropriate for men with a remaining life expectancy of at least 10 years. Accordingly, younger men with stage I-II colorectal cancers at diagnosis (or stage III colorectal cancer that has not recurred 5 years after treatment) who have no or minimal comorbidities and who are at increased risk for either a diagnosis of prostate cancer or mortality secondary to prostate cancer (patients who have a positive family history or are African-American, respectively) are most likely to experience more good outcomes than harmful ones as a result of undergoing PSA-based screening. PMID:24367864

  1. 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

  2. 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

  3. A study on relation of dietary fiber from different sources, acceptable daily intake of calcium and colorectal cancer of 30 to 45 years old.

    PubMed

    Wang, Dongjie; An, Yan; Zhu, Huifang; Yang, Libin

    2014-07-01

    This paper selects Jiashan, Zhejiang, the high incidence area of colorectal cancer in China, as research site and adopts case control as research method to study relative hazards of colorectal cancer, especially the relation between dietary factor and colorectal cancer. It makes a further understanding of the possible cause of high incidence of colorectal cancer in Jiashan in order to provide a scientific basis for the prevention of colorectal cancer. PMID:25016262

  4. 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