Chemopreventive effect of chalcone derivative, L2H17, in colon cancer development

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Xu, Shanmei; Chen, Minxiao; Chen, Wenbo; Hui, Junguo; Ji, Jiansong; Hu, Shuping; Zhou, Jianmin; Wang, Yi; Liang, Guang

2015-01-01

Colon cancer is the third most commonly diagnosed cancer and the second leading cause of cancer mortality worldwide. Chalcone and its derivatives are reported to exhibit anti-cancer effects in several cancer cell lines, including colon cancer cells. In addition, chalcones have advantages such as poor interaction with DNA and low risk of mutagenesity. In our previous study, a group of chalcone derivatives were synthesized and exhibited strong anti-inflammatory activities. In this study, we evaluated the anti-cancer effects of the chalcone derivative, L2H17, in colon cancer cells. The cytotoxicities of L2H17 on various colon cancer cell lines were investigated by MTT and clonogenic assay. Cell cycle and apoptosis analysis were performed to evaluate the molecular mechanism of L2H17-mediated inhibition of tumor growth. Also, scratch wound and matrigel invasion experiments were performed to estimate the cell migration and invasion after L2H17 treatment. Finally, we observed the anti-colon cancer effects of L2H17 in vivo. Our data show that compound L2H17 exhibited selective cytotoxic effect on colon cancer cells, via inducing G0/G1 cell cycle arrest and apoptosis in CT26.WT cells. Furthermore, L2H17 treatment decreased cell migration and invasion of CT26.WT cells. In addition, L2H17 possessed marked anti-tumor activity in vivo. The molecular mechanism of L2H17-mediated inhibition of tumor promotion and progression were function through inactivated NF-κB and Akt signaling pathways. All these findings show that L2H17 might be a potential growth inhibitory chalcones derivative for colon cancer cells

Does sex of the patient play a role in survival for MSI colorectal cancer?

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Adrian Tulin

2018-04-01

Full Text Available Microsatellite instability (MSI is a feature of colorectal tumors that develops as a result of inactivation of the DNA mismatch repair system. It is found in about 15% of all colorectal cancers and is an important prognostic molecular marker when assessing patients with colorectal cancer. It can influence prognosis and treatment decisions in both the advanced and early stages. Although in early stages this marker suggests a favorable prognosis and presents an important argument against adjuvant treatment in stage II disease, in metastatic stages it no longer associated with such an optimistic outcome. The present trial is a prospective, single-center study which included 122 colorectal cancer patients who were tested for MSI using immunohistochemistry. The trial included patients with stage II to IV colorectal cancer, treated in the Prof. Dr. Agrippa Ionescu Emergency Hospital, Bucharest, Romania. Follow-up data were collected during a 24-month period. The study attempted to determine whether differences exist in overall survival for MSI (microsatellite instability vs. MSS (microsatellite stable colorectal cancer and to ascertain whether sex of the patient influences prognosis in MSI patients, irrespective of stage or treatment. Results demonstrated no significant differences in survival for MSI vs MSS colorectal patients, and patients’ gender proved not to influence the outcome in MSI patients.

The role of the CpG island methylator phenotype on survival outcome in colon cancer.

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Kang, Ki Joo; Min, Byung Hoon; Ryu, Kyung Ju; Kim, Kyoung Mee; Chang, Dong Kyung; Kim, Jae J; Rhee, Jong Chul; Kim, Young Ho

2015-03-01

CpG island methylator phenotype (CIMP)- high colorectal cancers (CRCs) have distinct clinicopathologi-cal features from their CIMP-low/negative CRC counterparts. However, controversy exists regarding the prognosis of CRC according to the CIMP status. Therefore, this study examined the prognosis of Korean patients with colon cancer according to the CIMP status. Among a previous cohort pop-ulation with CRC, a total of 154 patients with colon cancer who had available tissue for DNA extraction were included in the study. CIMP-high was defined as ≥3/5 methylated mark-ers using the five-marker panel (CACNA1G, IGF2, NEUROG1, RUNX3, and SOCS1). CIMP-high and CIMP-low/neg-ative cancers were observed in 27 patients (17.5%) and 127 patients (82.5%), respectively. Multivariate analysis adjust-ing for age, gender, tumor location, tumor stage and CIMP and microsatellite instability (MSI) statuses indicated that CIMP-high colon cancers were associated with a significant increase in colon cancer-specific mortality (hazard ratio [HR], 3.23; 95% confidence interval [CI], 1.20 to 8.69; p=0.02). In microsatellite stable cancers, CIMP-high cancer had a poor survival outcome compared to CIMP-low/negative cancer (HR, 2.91; 95% CI, 1.02 to 8.27; p=0.04). Re-gardless of the MSI status, CIMP-high cancers had poor sur-vival outcomes in Korean patients. (Gut Liver, 2015;9202-207).

Microsatellite instability analysis in hereditary non-polyposis colon cancer using the Bethesda consensus panel of microsatellite markers in the absence of proband normal tissue

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Dourisboure Ricardo J

2006-01-01

Full Text Available Abstract Background Hereditary non-polyposis colon cancer (HNPCC is an autosomal dominant syndrome predisposing to the early development of various cancers including those of colon, rectum, endometrium, ovarium, small bowel, stomach and urinary tract. HNPCC is caused by germline mutations in the DNA mismatch repair genes, mostly hMSH2 or hMLH1. In this study, we report the analysis for genetic counseling of three first-degree relatives (the mother and two sisters of a male who died of colorectal adenocarcinoma at the age of 23. The family fulfilled strict Amsterdam-I criteria (AC-I with the presence of extracolonic tumors in the extended pedigree. We overcame the difficulty of having a proband post-mortem non-tumor tissue sample for MSI testing by studying the alleles carried by his progenitors. Methods Tumor MSI testing is described as initial screening in both primary and metastasis tumor tissue blocks, using the reference panel of 5 microsatellite markers standardized by the National Cancer Institute (NCI for the screening of HNPCC (BAT-25, BAT-26, D2S123, D5S346 and D17S250. Subsequent mutation analysis of the hMLH1 and hMSH2 genes was performed. Results Three of five microsatellite markers (BAT-25, BAT-26 and D5S346 presented different alleles in the proband's tumor as compared to those inherited from his parents. The tumor was classified as high frequency microsatellite instability (MSI-H. We identified in the HNPCC family a novel germline missense (c.1864C>A mutation in exon 12 of hMSH2 gene, leading to a proline 622 to threonine (p.Pro622Thr amino acid substitution. Conclusion This approach allowed us to establish the tumor MSI status using the NCI recommended panel in the absence of proband's non-tumor tissue and before sequencing the obligate carrier. According to the Human Gene Mutation Database (HGMD and the International Society for Gastrointestinal Hereditary Tumors (InSiGHT Database this is the first report of this mutation.

Overexpression of UbcH10 alternates the cell cycle profile and accelerate the tumor proliferation in colon cancer

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Hatoh Shinji

2009-03-01

Full Text Available Abstract Background UbcH10 participates in proper metaphase to anaphase transition, and abrogation of UbcH10 results in the premature separation of sister chromatids. To assess the potential role of UbcH10 in colon cancer progression, we analyzed the clinicopathological relevance of UbcH10 in colon cancer. Methods We firstly screened the expression profile of UbcH10 in various types of cancer tissues as well as cell lines. Thereafter, using the colon cancer cells line, we manipulated the expression of UbcH10 and evaluated the cell cycle profile and cellular proliferations. Furthermore, the clinicopathological significance of UbcH10 was immunohistologically evaluated in patients with colon cancer. Statistical analysis was performed using the student's t-test and Chi-square test. Results Using the colon cancer cells, depletion of UbcH10 resulted in suppression of cellular growth whereas overexpression of UbcH10 promoted the cellular growth and oncogenic cellular growth. Mitotic population was markedly alternated by the manipulation of UbcH10 expression. Immunohistochemical analysis indicated that UbcH10 was significantly higher in colon cancer tissue compared with normal colon epithelia. Furthermore, the clinicopathological evaluation revealed that UbcH10 was associated with high-grade histological tumors. Conclusion The results show the clinicopathological significance of UbcH10 in the progression of colon cancer. Thus UbcH10 may act as a novel biomarker in patients with colon cancer.

Development of an Anti-HER2 Monoclonal Antibody H2Mab-139 Against Colon Cancer.

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Kaneko, Mika K; Yamada, Shinji; Itai, Shunsuke; Kato, Yukinari

2018-02-01

Human epidermal growth factor receptor 2 (HER2) expression has been reported in several cancers, such as breast, gastric, lung, pancreatic, and colorectal cancers. HER2 is overexpressed in those cancers and is associated with poor clinical outcomes. Trastuzumab, a humanized anti-HER2 antibody, provides significant survival benefits for patients with HER2-overexpressing breast cancers and gastric cancers. In this study, we developed a novel anti-HER2 monoclonal antibody (mAb), H 2 Mab-139 (IgG 1 , kappa) and investigated it against colon cancers using flow cytometry, western blot, and immunohistochemical analyses. Flow cytometry analysis revealed that H 2 Mab-139 reacted with colon cancer cell lines, such as Caco-2, HCT-116, HCT-15, HT-29, LS 174T, COLO 201, COLO 205, HCT-8, SW1116, and DLD-1. Although H 2 Mab-139 strongly reacted with LN229/HER2 cells on the western blot, we did not observe a specific signal for HER2 in colon cancer cell lines. Immunohistochemical analyses revealed sensitive and specific reactions of H 2 Mab-139 against colon cancers, indicating that H 2 Mab-139 is useful in detecting HER2 overexpression in colon cancers using flow cytometry and immunohistochemical analyses.

SLC5A8 gene, a transporter of butyrate: a gut flora metabolite, is frequently methylated in African American colon adenomas.

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Hassan Brim

Full Text Available Colon cancer is one of the leading causes of cancer related deaths. Its impact on African Americans (AAs is higher than in the general population both in the incidence and mortality from the disease. Colon cancer aggressiveness in AAs as well as non-frequent check-ups and follow up in this population have been proposed as ways to explain the observed discrepancies. These facts made the detection of early carcinogenesis markers in this population a priority.Here, we analyzed 50 colon adenomas from AA patients for both microsatellite instability (MSI and the methylation status of SLC5A8 gene. This gene's product is involved in the transport of butyrate that has anti-proliferative properties through its effects on histone acetylation and gene expression. A proteomic analysis to check the expressed histones in adenoma and normal tissues was also performed.The analyzed samples displayed 82% (n = 41 methylation level of SLC5A8 gene in adenomas. The MSI-H (high adenoma were about 18% (n = 9 while the rest were mostly MSS (microsatellite stable with few MSI-L (Low. No association was found between SLC5A8 methylation and the MSI status. Also, there was no association between SLC5A8 methylation and the sex and age of the patients. However, there were more right sided adenomas with SLC5A8 methylation than the left sided ones. The proteomic analysis revealed distinct histone expression profiles between normal and adenoma tissues.SLC5A8 is highly methylated in AA colon adenomas which points to its potential use as a marker for early detection. The MSI rate is similar to that found in colon cancer tumors in AAs. These findings suggest that both processes stem from the same epigenetic and genetic events occurring at an early stage in colon carcinogenesis in AAs.

Dietary factors and microsatellite instability in sporadic colon carcinomas

NARCIS (Netherlands)

Diergaarde, B.; Braam, H.; Muijen, van G.N.P.; Ligtenberg, M.J.L.; Kok, F.J.; Kampman, E.

2003-01-01

Microsatellite instability (MSI) occurs in 10-20% of the sporadic colon carcinomas and appears to be primarily due to alterations in hMLH1 and hMSH2. Little is known about the role of diet in MSI-related colon carcinogenesis. We used data from a Dutch population-based case-control study on sporadic

Dietary factors and microsatellite instability in sporadic colon carcinomas.

NARCIS (Netherlands)

Diergaarde, B.; Braam, H.; Muijen, G.N.P. van; Ligtenberg, M.J.L.; Kok, F.J.; Kampman, E.

2003-01-01

Microsatellite instability (MSI) occurs in 10-20% of the sporadic colon carcinomas and appears to be primarily due to alterations in hMLH1 and hMSH2. Little is known about the role of diet in MSI-related colon carcinogenesis. We used data from a Dutch population-based case-control study on sporadic

mRNA/microRNA gene expression profile in microsatellite unstable colorectal cancer

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Calin George A

2007-08-01

Full Text Available Abstract Background Colorectal cancer develops through two main genetic instability pathways characterized by distinct pathologic features and clinical outcome. Results We investigated colon cancer samples (23 characterized by microsatellite stability, MSS, and 16 by high microsatellite instability, MSI-H for genome-wide expression of microRNA (miRNA and mRNA. Based on combined miRNA and mRNA gene expression, a molecular signature consisting of twenty seven differentially expressed genes, inclusive of 8 miRNAs, could correctly distinguish MSI-H versus MSS colon cancer samples. Among the differentially expressed miRNAs, various members of the oncogenic miR-17-92 family were significantly up-regulated in MSS cancers. The majority of protein coding genes were also up-regulated in MSS cancers. Their functional classification revealed that they were most frequently associated with cell cycle, DNA replication, recombination, repair, gastrointestinal disease and immune response. Conclusion This is the first report that indicates the existence of differences in miRNA expression between MSS versus MSI-H colorectal cancers. In addition, the work suggests that the combination of mRNA/miRNA expression signatures may represent a general approach for improving bio-molecular classification of human cancer.

The Msi Family of RNA-Binding Proteins Function Redundantly as Intestinal Oncoproteins

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Ning Li

2015-12-01

Full Text Available Members of the Msi family of RNA-binding proteins have recently emerged as potent oncoproteins in a range of malignancies. MSI2 is highly expressed in hematopoietic cancers, where it is required for disease maintenance. In contrast to the hematopoietic system, colorectal cancers can express both Msi family members, MSI1 and MSI2. Here, we demonstrate that, in the intestinal epithelium, Msi1 and Msi2 have analogous oncogenic effects. Further, comparison of Msi1/2-induced gene expression programs and transcriptome-wide analyses of Msi1/2-RNA-binding targets reveal significant functional overlap, including induction of the PDK-Akt-mTORC1 axis. Ultimately, we demonstrate that concomitant loss of function of both MSI family members is sufficient to abrogate the growth of human colorectal cancer cells, and Msi gene deletion inhibits tumorigenesis in several mouse models of intestinal cancer. Our findings demonstrate that MSI1 and MSI2 act as functionally redundant oncoproteins required for the ontogeny of intestinal cancers.

Colon cancer

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Colorectal cancer; Cancer - colon; Rectal cancer; Cancer - rectum; Adenocarcinoma - colon; Colon - adenocarcinoma; Colon carcinoma ... eat may play a role in getting colon cancer. Colon cancer may be linked to a high-fat, ...

Conventional colon adenomas harbor various disturbances in microsatellite stability and contain micro-serrated foci with microsatellite instability.

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Piotr Lewitowicz

Full Text Available Colorectal cancer belongs to the most frequent occurring malignancies. A prediction of the clinical outcome and appropriate choice of neoadjuvant chemotherapy needs personalized insight to the main driving pathways. Because most CRCs have polyps as progenitor lesions, studying the pathways driving to adenomagenesis is no less important.Our purpose was the evaluation of microsatellite stability status within conventional colon adenomas and also β-catenin, BRAFV600E and p53 contribution.The cohort included 101 cases of typical colon adenomas with high grade epithelial dysplasia according to WHO. An immunohistochemistry method was used for the depiction of the expression of targeted proteins, as also their heterogeneity.Generally, we noted a 10% frequency of MSI events where MSI-H reached a 5% share occurred within the left colon and rectal polyps. β-catenin nuclear overexpression was noted with a 70% frequency and p53 with close to a 24% frequency. In addition, we found a presence of micro-serration foci more often within tubular adenomas, where focal MSI took place more often. Our results indicate that MSI events occur more often than had been theorized earlier. It results in tumour heterogeneity, more complex underlying pathways and finally ontogenetic molecular-diversity of tumours besides similar occurring histopathological features.

Transforming growth factor beta receptor 2 (TGFBR2 changes sialylation in the microsatellite unstable (MSI Colorectal cancer cell line HCT116.

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Jennifer Lee

Full Text Available Aberrant glycosylation is a common feature of many malignancies including colorectal cancers (CRCs. About 15% of CRC show the microsatellite instability (MSI phenotype that is associated with a high frequency of biallelic frameshift mutations in the A10 coding mononucleotide microsatellite of the transforming growth factor beta receptor 2 (TGFBR2 gene. If and how impaired TGFBR2 signaling in MSI CRC cells affects cell surface glycan pattern is largely unexplored. Here, we used the TGFBR2-deficient MSI colon carcinoma cell line HCT116 as a model system. Stable clones conferring doxycycline (dox-inducible expression of a single copy wildtype TGFBR2 transgene were generated by recombinase-mediated cassette exchange (RMCE. In two independent clones, dox-inducible expression of wildtype TGFBR2 protein and reconstitution of its signaling function was shown. Metabolic labeling experiments using the tritiated sialic acid precursor N-acetyl-D-mannosamine (ManNAc revealed a significant decline (∼30% of its incorporation into newly synthesized sialoglycoproteins in a TGFBR2-dependent manner. In particular, we detected a significant decrease of sialylated ß1-integrin upon reconstituted TGFBR2 signaling which did not influence ß1-integrin protein turnover. Notably, TGFBR2 reconstitution did not affect the transcript levels of any of the known human sialyltransferases when examined by real-time RT- PCR analysis. These results suggest that reconstituted TGFBR2 signaling in an isogenic MSI cell line model system can modulate sialylation of cell surface proteins like ß1-integrin. Moreover, our model system will be suitable to uncover the underlying molecular mechanisms of altered MSI tumor glycobiology.

Genetic variation in bone morphogenetic protein (BMP) and colon and rectal cancer

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Slattery, Martha L.; Lundgreen, Abbie; Herrick, Jennifer S.; Kadlubar, Susan; Caan, Bette J.; Potter, John D.; Wolff, Roger K.

2011-01-01

Bone morphogenetic proteins (BMP) are part of the TGF-β-signaling pathway; genetic variation in these genes may be involved in colorectal cancer. In this study we evaluated the association between genetic variation in BMP1 (11 tagSNPs), BMP2 (5 tagSNPs), BMP4 (3 tagSNPs), BMPR1A (9 tagSNPs), BMPR1B (21 tagSNPs), BMPR2 (11 tagSNPs), and GDF10 (7 tagSNPs) with risk of colon and rectal cancer and tumor molecular phenotype. We used data from population-based case-control studies (colon cancer n=1574 cases, 1970 controls; rectal cancer n=791 cases, 999 controls). We observed that genetic variation in BMPR1A, BMPR1B, BMPR2, BMP2, and BMP4 was associated with risk of developing colon cancer, with 20 to 30% increased risk for most high-risk genotypes. A summary of high-risk genotypes showed over a twofold increase in colon cancer risk at the upper risk category (OR 2.49 95% CI 1.95, 3.18). BMPR2, BMPR1B, BMP2, and GDF10 were associated with rectal cancer. BMPR2 rs2228545 was associated with an almost twofold increased risk of rectal cancer. The risk associated with the highest category of the summary score for rectal cancer was 2.97 (95% CI 1.87, 4.72). Genes in the BMP-signaling pathway were consistently associated with CIMP+ status in combination with both KRAS-mutated and MSI tumors. BMP genes interacted statistically significantly with other genes in the TGF-β-signaling pathway, including TGFβ1, TGFβR1, Smad 3, Smad 4, and Smad 7. Our data support a role for genetic variation in BMP-related genes in the etiology of colon and rectal cancer. One possible mechanism is via the TGF-β-signaling pathway. PMID:21387313

A multifactorial likelihood model for MMR gene variant classification incorporating probabilities based on sequence bioinformatics and tumor characteristics: a report from the Colon Cancer Family Registry.

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Thompson, Bryony A; Goldgar, David E; Paterson, Carol; Clendenning, Mark; Walters, Rhiannon; Arnold, Sven; Parsons, Michael T; Michael D, Walsh; Gallinger, Steven; Haile, Robert W; Hopper, John L; Jenkins, Mark A; Lemarchand, Loic; Lindor, Noralane M; Newcomb, Polly A; Thibodeau, Stephen N; Young, Joanne P; Buchanan, Daniel D; Tavtigian, Sean V; Spurdle, Amanda B

2013-01-01

Mismatch repair (MMR) gene sequence variants of uncertain clinical significance are often identified in suspected Lynch syndrome families, and this constitutes a challenge for both researchers and clinicians. Multifactorial likelihood model approaches provide a quantitative measure of MMR variant pathogenicity, but first require input of likelihood ratios (LRs) for different MMR variation-associated characteristics from appropriate, well-characterized reference datasets. Microsatellite instability (MSI) and somatic BRAF tumor data for unselected colorectal cancer probands of known pathogenic variant status were used to derive LRs for tumor characteristics using the Colon Cancer Family Registry (CFR) resource. These tumor LRs were combined with variant segregation within families, and estimates of prior probability of pathogenicity based on sequence conservation and position, to analyze 44 unclassified variants identified initially in Australasian Colon CFR families. In addition, in vitro splicing analyses were conducted on the subset of variants based on bioinformatic splicing predictions. The LR in favor of pathogenicity was estimated to be ~12-fold for a colorectal tumor with a BRAF mutation-negative MSI-H phenotype. For 31 of the 44 variants, the posterior probabilities of pathogenicity were such that altered clinical management would be indicated. Our findings provide a working multifactorial likelihood model for classification that carefully considers mode of ascertainment for gene testing. © 2012 Wiley Periodicals, Inc.

Colon Cancer Tumorigenesis Initiated by the H1047R Mutant PI3K.

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Alexander E Yueh

Full Text Available The phosphoinositide 3-kinase (PI3K signaling pathway is critical for multiple important cellular functions, and is one of the most commonly altered pathways in human cancers. We previously developed a mouse model in which colon cancers were initiated by a dominant active PI3K p110-p85 fusion protein. In that model, well-differentiated mucinous adenocarcinomas developed within the colon and initiated through a non-canonical mechanism that is not dependent on WNT signaling. To assess the potential relevance of PI3K mutations in human cancers, we sought to determine if one of the common mutations in the human disease could also initiate similar colon cancers. Mice were generated expressing the Pik3caH1047R mutation, the analog of one of three human hotspot mutations in this gene. Mice expressing a constitutively active PI3K, as a result of this mutation, develop invasive adenocarcinomas strikingly similar to invasive adenocarcinomas found in human colon cancers. These tumors form without a polypoid intermediary and also lack nuclear CTNNB1 (β-catenin, indicating a non-canonical mechanism of tumor initiation mediated by the PI3K pathway. These cancers are sensitive to dual PI3K/mTOR inhibition indicating dependence on the PI3K pathway. The tumor tissue remaining after treatment demonstrated reduction in cellular proliferation and inhibition of PI3K signaling.

Proteogenomic characterization of human colon and rectal cancer

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Zhang, Bing; Wang, Jing; Wang, Xiaojing; Zhu, Jing; Liu, Qi; Shi, Zhiao; Chambers, Matthew C.; Zimmerman, Lisa J.; Shaddox, Kent F.; Kim, Sangtae; Davies, Sherri; Wang, Sean; Wang, Pei; Kinsinger, Christopher; Rivers, Robert; Rodriguez, Henry; Townsend, Reid; Ellis, Matthew; Carr, Steven A.; Tabb, David L.; Coffey, Robert J.; Slebos, Robbert; Liebler, Daniel

2014-09-18

We analyzed proteomes of colon and rectal tumors previously characterized by the Cancer Genome Atlas (TCGA) and performed integrated proteogenomic analyses. Protein sequence variants encoded by somatic genomic variations displayed reduced expression compared to protein variants encoded by germline variations. mRNA transcript abundance did not reliably predict protein expression differences between tumors. Proteomics identified five protein expression subtypes, two of which were associated with the TCGA "MSI/CIMP" transcriptional subtype, but had distinct mutation and methylation patterns and associated with different clinical outcomes. Although CNAs showed strong cis- and trans-effects on mRNA expression, relatively few of these extend to the protein level. Thus, proteomics data enabled prioritization of candidate driver genes. Our analyses identified HNF4A, a novel candidate driver gene in tumors with chromosome 20q amplifications. Integrated proteogenomic analysis provides functional context to interpret genomic abnormalities and affords novel insights into cancer biology.

Differential expression of DHHC9 in microsatellite stable and instable human colorectal cancer subgroups

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Mansilla, Francisco; Birkenkamp-Demtröder, Karin; Kruhøffer, Mogens

2007-01-01

validated these findings, showing a significant two-fold (log 2) upregulation of DHHC9 transcript (PGenes known to interact with DHHC9 as H-Ras or N-Ras did not show expression...... cell lines significantly. In conclusion, DHHC9 is a gastrointestinal-related protein highly expressed in MSS colon tumours. The palmitoyl transferase activity, modifying N-Ras and H-Ras, suggests DHHC9 as a target for anticancer drug design.British Journal of Cancer advance online publication, 22 May...... differences between MSS and MSI. Immunohistochemical analysis was performed on 60 colon adenocarcinomas, previously analysed on microarrays, as well as on tissue microarrays with 40 stage I-IV tumours and 46 tumours from different organ sites. DHHC9 protein was strongly expressed in MSS compared to MSI...

Detection of mismatch repair gene germline mutation carrier among Chinese population with colorectal cancer

International Nuclear Information System (INIS)

Jin, Hei-Ying; Zhao, Ronghua; Liu, Xiufang; Li, Vicky Ka Ming; Ding, Yijiang; Yang, Bolin; Geng, Jianxiang; Lai, Rensheng; Ding, Shuqing; Ni, Min

2008-01-01

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant syndrome. The National Cancer Institute (NCI) has recommended the Revised Bethesda guidelines for screening HNPCC. There has been a great deal of research on the value of these tests in other countries. However, literature about the Chinese population is scarce. Our objective is to detect and study microsatellite instability (MSI) and mismatch repair (MMR) gene germline mutation carriers among a Chinese population with colorectal cancer. In 146 prospectively recruited consecutive patients with clinically proven colorectal cancer, MSI carriers were identified by analysis of tumor tissue using multiplex fluorescence polymerase chain reaction (PCR) using the NCI recommended panel and classified into microsatellite instability-low (MSI-L), microsatellite instability-high (MSI-H) and microsatellite stable (MSS) groups. Immunohistochemical staining for MSH2, MSH6 and MLH1 on tissue microarrays (TMAs) was performed, and methylation of the MLH1 promoter was analyzed by quantitative methylation specific PCR (MSP). Germline mutation analysis of blood samples was performed for MSH2, MSH6 and MLH1 genes. Thirty-four out of the 146 colorectal cancers (CRCs, 23.2%) were MSI, including 19 MSI-H CRCs and 15 MSI-L CRCS. Negative staining for MSH2 was found in 8 CRCs, negative staining for MSH6 was found in 6 CRCs. One MSI-H CRC was negative for both MSH6 and MSH2. Seventeen CRCs stained negatively for MLH1. MLH1 promoter methylation was determined in 34 MSI CRCs. Hypermethylation of the MLH1 promoter occurred in 14 (73.7%) out of 19 MSI-H CRCs and 5 (33.3%) out of 15 MSI-L CRCs. Among the 34 MSI carriers and one MSS CRC with MLH1 negative staining, 8 had a MMR gene germline mutation, which accounted for 23.5% of all MSI colorectal cancers and 5.5% of all the colorectal cancers. Five patients harbored MSH2 germline mutations, and three patients harbored MSH6 germline mutations. None of the patients had an MLH

The "Fas counterattack" is not an active mode of tumor immune evasion in colorectal cancer with high-level microsatellite instability.

LENUS (Irish Health Repository)

Houston, Aileen M

2012-02-03

Microsatellite instability (MSI) is an alternative pathway of colorectal carcinogenesis. It is found in 10% to 15% of sporadic colorectal neoplasms and is characterized by failure of the DNA mismatch-repair system. High-level MSI (MSI-H) is associated with tumor-infiltrating lymphocytes (TILs) and a favorable prognosis. Expression of Fas ligand (FasL\\/CD95L) by cancer cells may mediate tumor immune privilege by inducing apoptosis of antitumor immune cells. The aim of this study was to investigate the relationship between FasL expression and MSI status in primary colon tumors. Using immunohistochemistry, we detected FasL expression in 91 colorectal carcinoma specimens, previously classified according to the level of MSI as MSI-H (n = 26), MSI-low (MSI-L) (n = 29), and microsatellite stable (n = 36). Tumor-infiltrating lymphocyte density was quantified by immunohistochemical staining for CD3. MSI-H tumors were significantly associated with reduced frequency (P = .04) and intensity (P = .066) of FasL expression relative to non-MSI-H (ie, microsatellite stable and MSI-L) tumors. Higher FasL staining intensity correlated with reduced TIL density (P = .059). Together, these findings suggest that the abundance of TILs found in MSI-H tumors may be due to the failure of these tumor cells to up-regulate FasL and may explain, in part, the improved prognosis associated with these tumors.

Models for Immune Response and Immune Evasion in MSI Cancer and Lynch Syndrome

OpenAIRE

Özcan, Mine

2017-01-01

Microsatellite-unstable (MSI) cancers occurring in the context of the hereditary Lynch syndrome or as sporadic cancers elicit pronounced tumor-specific immune responses. The pronounced immune response was shown to be closely associated with frameshift peptides (FSP) that are generated as a result of deficiency in DNA mismatch repair system leading to insertion/deletion mutations in coding microsatellites (cMS). FSP neoantigens are long antigenic amino acid stretches that bear m...

Targeted sequencing of established and candidate colorectal cancer genes in the Colon Cancer Family Registry Cohort.

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Raskin, Leon; Guo, Yan; Du, Liping; Clendenning, Mark; Rosty, Christophe; Lindor, Noralane M; Gruber, Stephen B; Buchanan, Daniel D

2017-11-07

The underlying genetic cause of colorectal cancer (CRC) can be identified for 5-10% of all cases, while at least 20% of CRC cases are thought to be due to inherited genetic factors. Screening for highly penetrant mutations in genes associated with Mendelian cancer syndromes using next-generation sequencing (NGS) can be prohibitively expensive for studies requiring large samples sizes. The aim of the study was to identify rare single nucleotide variants and small indels in 40 established or candidate CRC susceptibility genes in 1,046 familial CRC cases (including both MSS and MSI-H tumor subtypes) and 1,006 unrelated controls from the Colon Cancer Family Registry Cohort using a robust and cost-effective DNA pooling NGS strategy. We identified 264 variants in 38 genes that were observed only in cases, comprising either very rare (minor allele frequency cancer susceptibility genes BAP1, CDH1, CHEK2, ENG, and MSH3 . For the candidate CRC genes, we identified likely pathogenic variants in the helicase domain of POLQ and in the LRIG1 , SH2B3 , and NOS1 genes and present their clinicopathological characteristics. Using a DNA pooling NGS strategy, we identified novel germline mutations in established CRC susceptibility genes in familial CRC cases. Further studies are required to support the role of POLQ , LRIG1 , SH2B3 and NOS1 as CRC susceptibility genes.

CDX2 prognostic value in stage II/III resected colon cancer is related to CMS classification.

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Pilati, C; Taieb, J; Balogoun, R; Marisa, L; de Reyniès, A; Laurent-Puig, P

2017-05-01

Caudal-type homeobox transcription factor 2 (CDX2) is involved in colon cancer (CC) oncogenesis and has been proposed as a prognostic biomarker in patients with stage II or III CC. We analyzed CDX2 expression in a series of 469 CC typed for the new international consensus molecular subtype (CMS) classification, and we confirmed results in a series of 90 CC. Here, we show that lack of CDX2 expression is only present in the mesenchymal subgroup (CMS4) and in MSI-immune tumors (CMS1) and not in CMS2 and CMS3 colon cancer. Although CDX2 expression was a globally independent prognostic factor, loss of CDX2 expression is not associated with a worse prognosis in the CMS1 group, but is highly prognostic in CMS4 patients for both relapse free and overall survival. Similarly, lack of CDX2 expression was a bad prognostic factor in MSS patients, but not in MSI. Our work suggests that combination of the consensual CMS classification and lack of CDX2 expression could be a useful marker to identify CMS4/CDX2-negative patients with a very poor prognosis. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Immunohistochemical and DNA sequencing analysis on human mismatch repair gene MLH1 in cervical squamous cell carcinoma with LOH of this gene

NARCIS (Netherlands)

Hu, X.; Guo, Z.; Pang, T.; Li, Q.; Afink, G.; Pontén, J.

2000-01-01

BACKGROUND: The human MLH1 gene (hMLH1) is one of the DNA mismatch repair genes. Defects in these genes are believed to be the underlying cause of microsatellite instability (MSI). MSI has been demonstrated in many human cancers such as colon cancer and some female-specific tumors. The hMLH1 gene

Role of neutral ceramidase in colon cancer.

Science.gov (United States)

García-Barros, Mónica; Coant, Nicolas; Kawamori, Toshihiko; Wada, Masayuki; Snider, Ashley J; Truman, Jean-Philip; Wu, Bill X; Furuya, Hideki; Clarke, Christopher J; Bialkowska, Agnieszka B; Ghaleb, Amr; Yang, Vincent W; Obeid, Lina M; Hannun, Yusuf A

2016-12-01

Alterations in sphingolipid metabolism, especially ceramide and sphingosine 1-phosphate, have been linked to colon cancer, suggesting that enzymes of sphingolipid metabolism may emerge as novel regulators and targets in colon cancer. Neutral ceramidase (nCDase), a key enzyme in sphingolipid metabolism that hydrolyzes ceramide into sphingosine, is highly expressed in the intestine; however, its role in colon cancer has not been defined. Here we show that molecular and pharmacological inhibition of nCDase in colon cancer cells increases ceramide, and this is accompanied by decreased cell survival and increased apoptosis and autophagy, with minimal effects on noncancerous cells. Inhibition of nCDase resulted in loss of β-catenin and inhibition of ERK, components of pathways relevant for colon cancer development. Furthermore, inhibition of nCDase in a xenograft model delayed tumor growth and increased ceramide while decreasing proliferation. It is noteworthy that mice lacking nCDase treated with azoxymethane were protected from tumor formation. Taken together, these studies show that nCDase is pivotal for regulating initiation and development of colon cancer, and these data suggest that this enzyme is a suitable and novel target for colon cancer therapy.-García-Barros, M., Coant, N., Kawamori, T., Wada, M., Snider, A. J., Truman, J.-P., Wu, B. X., Furuya, H., Clarke, C. J., Bialkowska, A. B., Ghaleb, A., Yang, V. W., Obeid, L. M., Hannun, Y. A. Role of neutral ceramidase in colon cancer. © FASEB.

CT in colon cancer

International Nuclear Information System (INIS)

Fujita, Nobuyuki; Hasegawa, Takashi; Kubo, Kozo; Ogawa, Hajime; Sato, Yukihiko; Tomita, Masayoshi; Hanawa, Makoto; Matsuzawa, Tohru; Nishioka, Ken

1990-01-01

CT pictures from 59 lesions of advanced colon cancer including rectal cancer were reviewed to evaluate a role of CT in preoperative staging diagnosis. CT findings were recorded following general rules for clinical and pathological studies on cancer of colon rectum and anus, proposed by Japanese society for cancer of colon and rectum. Tumors were detected in 90% of advanced colon cancers. Sensitivity in local extension (S factor) was 58.0%. Sensitivity in lymphonode involvement (N factor) was 50.0%. Sensitivity in final staging diagnosis, dividing colon cancer into two groups below st II and above st III, was 63.3%. Further study should be necessitated to provide useful information for preoperative staging diagnosis of colon cancer. (author)

Complex pattern of immune evasion in MSI colorectal cancer.

Science.gov (United States)

Ozcan, Mine; Janikovits, Jonas; von Knebel Doeberitz, Magnus; Kloor, Matthias

2018-01-01

Mismatch repair (MMR)-deficient cancers accumulate multiple insertion/deletion mutations at coding microsatellites (cMS), which give rise to frameshift peptide neoantigens. The high mutational neoantigen load of MMR-deficient cancers is reflected by pronounced anti-tumoral immune responses of the host and high responsiveness towards immune checkpoint blockade. However, immune evasion mechanisms can interfere with the immune response against MMR-deficient tumors. We here performed a comprehensive analysis of immune evasion in MMR-deficient colorectal cancers, focusing on HLA class I-mediated antigen presentation. 72% of MMR-deficient colorectal cancers of the DFCI database harbored alterations affecting genes involved in HLA class I-mediated antigen presentation, and 54% of these mutations were predicted to abrogate function. Mutations affecting the HLA class I transactivator NLRC5 were observed as a potential new immune evasion mechanism in 26% (6% abrogating) of the analyzed tumors. NLRC5 mutations in MMR-deficient cancers were associated with decreased levels of HLA class I antigen expression. In summary, the majority of MMR-deficient cancers display mutations interfering with HLA class I antigen presentation that reflect active immune surveillance and immunoselection during tumor development. Clinical studies focusing on immune checkpoint blockade in MSI cancer should account for the broad variety of immune evasion mechanisms as potential biomarkers of therapy success.

CT Findings of Colonic Complications Associated with Colon Cancer

International Nuclear Information System (INIS)

Kim, Sang Won; Shin, Hyeong Cheol; Kim, Il Young; Kim, Young Tong; Kim, Chang Jin

2010-01-01

A broad spectrum of colonic complications can occur in patients with colon cancer. Clinically, some of these complications can obscure the presence of underlying malignancies in the colon and these complications may require emergency surgical management. The complications of the colon that can be associated with colon cancer include obstruction, perforation, abscess formation, acute appendicitis, ischemic colitis and intussusception. Although the majority of these complications only rarely occur, familiarity with the various manifestations of colon cancer complications will facilitate making an accurate diagnosis and administering prompt management in these situations. The purpose of this pictorial essay is to review the CT appearance of the colonic complications associated with colon cancer

CT Findings of Colonic Complications Associated with Colon Cancer

Energy Technology Data Exchange (ETDEWEB)

Kim, Sang Won; Shin, Hyeong Cheol; Kim, Il Young; Kim, Young Tong; Kim, Chang Jin [Cheonan Hospital, Soonchunhyang University, Cheonan (Korea, Republic of)

2010-04-15

A broad spectrum of colonic complications can occur in patients with colon cancer. Clinically, some of these complications can obscure the presence of underlying malignancies in the colon and these complications may require emergency surgical management. The complications of the colon that can be associated with colon cancer include obstruction, perforation, abscess formation, acute appendicitis, ischemic colitis and intussusception. Although the majority of these complications only rarely occur, familiarity with the various manifestations of colon cancer complications will facilitate making an accurate diagnosis and administering prompt management in these situations. The purpose of this pictorial essay is to review the CT appearance of the colonic complications associated with colon cancer.

Colon cancer associated transcripts in human cancers.

Science.gov (United States)

Chen, Yincong; Xie, Haibiao; Gao, Qunjun; Zhan, Hengji; Xiao, Huizhong; Zou, Yifan; Zhang, Fuyou; Liu, Yuchen; Li, Jianfa

2017-10-01

Long non-coding RNAs serve as important regulators in complicated cellular activities, including cell differentiation, proliferation and death. Dysregulation of long non-coding RNAs occurs in the formation and progression of cancers. The family of colon cancer associated transcripts, long non-coding RNAs colon cancer associated transcript-1 and colon cancer associated transcript-2 are known as oncogenes involved in various cancers. Colon cancer associated transcript-1 is a novel lncRNA located in 8q24.2, and colon cancer associated transcript-2 maps to the 8q24.21 region encompassing rs6983267. Colon cancer associated transcripts have close associations with clinical characteristics, such as lymph node metastasis, high TNM stage and short overall survival. Knockdown of them can reverse the malignant phenotypes of cancer cells, including proliferation, migration, invasion and apoptosis. Moreover, they can increase the expression level of c-MYC and oncogenic microRNAs via activating a series of complex mechanisms. In brief, the family of colon cancer associated transcripts may serve as potential biomarkers or therapeutic targets for human cancers. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

H2S-induced S-sulfhydration of lactate dehydrogenase a (LDHA) stimulates cellular bioenergetics in HCT116 colon cancer cells.

Science.gov (United States)

Untereiner, Ashley A; Oláh, Gabor; Módis, Katalin; Hellmich, Mark R; Szabo, Csaba

2017-07-15

Cystathionine-β-synthase (CBS) is upregulated and hydrogen sulfide (H 2 S) production is increased in colon cancer cells. The functional consequence of this response is stimulation of cellular bioenergetics and tumor growth and proliferation. Lactate dehydrogenase A (LDHA) is also upregulated in various colon cancer cells and has been previously implicated in tumor cell bioenergetics and proliferation. In the present study, we sought to determine the potential interaction between the H 2 S pathway and LDH activity in the control of bioenergetics and proliferation of colon cancer, using the colon cancer line HCT116. Low concentrations of GYY4137 (a slow-releasing H 2 S donor) enhanced mitochondrial function (oxygen consumption, ATP production, and spare respiratory capacity) and glycolysis in HCT116 cells. SiRNA-mediated transient silencing of LDHA attenuated the GYY4137-induced stimulation of mitochondrial respiration, but not of glycolysis. H 2 S induced the S-sulfhydration of Cys163 in recombinant LDHA, and stimulated LDHA activity. The H 2 S-induced stimulation of LDHA activity was absent in C163A LDHA. As shown in HCT116 cell whole extracts, in addition to LDHA activation, GYY4137 also stimulated LDHB activity, although to a smaller extent. Total cellular lactate and pyruvate measurements showed that in HCT116 cells LDHA catalyzes the conversion of pyruvate to lactate. Total cellular lactate levels were increased by GYY4137 in wild-type cells (but not in cells with LDHA silencing). LDHA silencing sensitized HCT116 cells to glucose oxidase (GOx)-induced oxidative stress; this was further exacerbated with GYY4137 treatment. Treatment with low concentrations of GYY4137 (0.3mM) or GOx (0.01U/ml) significantly increased the proliferation rate of HCT116 cells; the effect of GOx, but not the effect of GYY4137 was attenuated by LDHA silencing. The current report points to the involvement of LDHA in the stimulatory effect of H 2 S on mitochondrial respiration in colon

[A case of metastatic gastric cancer originating from transverse colon cancer].

Science.gov (United States)

Nushijima, Youichirou; Nakano, Katsutoshi; Sugimoto, Keishi; Nakaguchi, Kazunori; Kan, Kazuomi; Maruyama, Hirohide; Doi, Sadayuki; Okamura, Shu; Murata, Kohei

2014-11-01

Metastatic gastric cancer is uncommon, and metastasis of colorectal cancer to the stomach is extremely rare. We report a case of metastatic gastric cancer that originated from transverse colon cancer. A 52-year-old woman underwent a left hemicolectomy and D3 lymph node dissection based on a diagnosis of transverse colon cancer. The pathology results were as follows: mucinous adenocarcinoma, type 2, 6 × 11 cm, ss, ly1 v1, pm (-), dm (-), n1 (+), P0, H0, M0, Stage IIIa. The patient received XELOX as postoperative adjuvant therapy for 6 months. One year and 3 months after the left hemicolectomy, gastroscopy revealed a submucosal tumor in the lower body of the stomach and an incipient cancer in the cardia of the stomach, and a colonoscopy revealed an incipient cancer in the transverse colon. An endoscopic ultrasonography fine needle aspiration biopsy of the submucosal tumor in the lower body of the stomach was performed. Histology showed that this tumor was a mucinous adenocarcinoma similar to the primary transverse colon cancer, which led to a diagnosis of metastatic gastric cancer originating from transverse colon cancer. Distant metastasis was not detected. Endoscopic submucosal dissection of the incipient gastric cancer was performed, as were distal gastrectomy and partial colectomy. Peritoneal dissemination and para-aortic lymph node recurrence were detected 7 months after the second surgery.

High hRFI expression correlates with resistance to Fluoro pyrimidines in human colon cancer cell lines and in xenografts

International Nuclear Information System (INIS)

Sasaki, S.; Tokyo Univ., Tokyo; Watanabe, T.; Konishi, T.; Kitayama, J.; Nagawa, H.; Kobunai, T.

2005-01-01

We previously reported that the over-expression of hRFI, a protein preferentially expressed in the digestive tract regions of several cancers, exhibited a tendency to inhibit TNF-α induced apoptosis. In this study, we sought to determine the potential effect of hRFI expression on the sensitivity to 5-fluorouracil (5-FU) and/or other fluoro pyrimidines. For the whole lysates of 8 colon cancer cell lines, we performed Western blotting with anti-hRFI antibody and analyzed the correlations between the expression level of hRFI and the cell lines' sensitivity to 5-FU induced apoptosis. Furthermore, for a tissue micro array consisting of 32 xenograft derived human cancer cell lines, we examined the expression levels of hRFI and survivin by immunohistochemical staining, and analyzed the correlations between the expression of each protein and the sensitivity to several chemotherapeutic agents in the xenografts examined. Both in colon cancer cell lines and in xenografts, the expression level of hRFI was correlated with resistance to 5-FU and its derivatives. This evidence suggests that hRFI may be a marker predicting the response to fluorouracil derived chemotherapeutic agents and that the reduction of the expression level of hRFI might improve the outcome of chemotherapy

Acetylcholine release by human colon cancer cells mediates autocrine stimulation of cell proliferation.

Science.gov (United States)

Cheng, Kunrong; Samimi, Roxana; Xie, Guofeng; Shant, Jasleen; Drachenberg, Cinthia; Wade, Mark; Davis, Richard J; Nomikos, George; Raufman, Jean-Pierre

2008-09-01

Most colon cancers overexpress M3 muscarinic receptors (M3R), and post-M3R signaling stimulates human colon cancer cell proliferation. Acetylcholine (ACh), a muscarinic receptor ligand traditionally regarded as a neurotransmitter, may be produced by nonneuronal cells. We hypothesized that ACh release by human colon cancer cells results in autocrine stimulation of proliferation. H508 human colon cancer cells, which have robust M3R expression, were used to examine effects of muscarinic receptor antagonists, acetylcholinesterase inhibitors, and choline transport inhibitors on cell proliferation. A nonselective muscarinic receptor antagonist (atropine), a selective M3R antagonist (p-fluorohexahydro-sila-difenidol hydrochloride), and a choline transport inhibitor (hemicholinum-3) all inhibited unstimulated H508 colon cancer cell proliferation by approximately 40% (P<0.005). In contrast, two acetylcholinesterase inhibitors (eserine-hemisulfate and bis-9-amino-1,2,3,4-tetrahydroacridine) increased proliferation by 2.5- and 2-fold, respectively (P<0.005). By using quantitative real-time PCR, expression of choline acetyltransferase (ChAT), a critical enzyme for ACh synthesis, was identified in H508, WiDr, and Caco-2 colon cancer cells. By using high-performance liquid chromatography-electrochemical detection, released ACh was detected in H508 and Caco-2 cell culture media. Immunohistochemistry in surgical specimens revealed weak or no cytoplasmic staining for ChAT in normal colon enterocytes (n=25) whereas half of colon cancer specimens (n=24) exhibited moderate to strong staining (P<0.005). We conclude that ACh is an autocrine growth factor in colon cancer. Mechanisms that regulate colon epithelial cell production and release of ACh warrant further investigation.

Meat and fish consumption, APC gene mutations and hMLH1 expression in colon and rectal cancer: a prospective cohort study (the Netherlands)

NARCIS (Netherlands)

Luchtenborg, M.; Weijenberg, M.P.; Goeij, de A.F.P.M.; Wark, P.A.; Brink, M.; Roemen, G.M.J.M.; Lentjes, M.H.F.M.; Bruine, de A.P.; Goldbohm, R.A.; Veer, van 't P.; Brandt, van den P.A.

2005-01-01

Objective:The aim of this study was to investigate the associations between meat and fish consumption and APC mutation status and hMLH1 expression in colon and rectal cancer. Methods:The associations were investigated in the Netherlands Cohort Study, and included 434 colon and 154 rectal cancer

Colon and rectal cancer survival by tumor location and microsatellite instability: the Colon Cancer Family Registry.

Science.gov (United States)

Phipps, Amanda I; Lindor, Noralane M; Jenkins, Mark A; Baron, John A; Win, Aung Ko; Gallinger, Steven; Gryfe, Robert; Newcomb, Polly A

2013-08-01

Cancers in the proximal colon, distal colon, and rectum are frequently studied together; however, there are biological differences in cancers across these sites, particularly in the prevalence of microsatellite instability. We assessed the differences in survival by colon or rectal cancer site, considering the contribution of microsatellite instability to such differences. This is a population-based prospective cohort study for cancer survival. This study was conducted within the Colon Cancer Family Registry, an international consortium. Participants were identified from population-based cancer registries in the United States, Canada, and Australia. Information on tumor site, microsatellite instability, and survival after diagnosis was available for 3284 men and women diagnosed with incident invasive colon or rectal cancer between 1997 and 2002, with ages at diagnosis ranging from 18 to 74. Cox regression was used to calculate hazard ratios for the association between all-cause mortality and tumor location, overall and by microsatellite instability status. Distal colon (HR, 0.59; 95% CI, 0.49-0.71) and rectal cancers (HR, 0.68; 95% CI, 0.57-0.81) were associated with lower mortality than proximal colon cancer overall. Compared specifically with patients with proximal colon cancer exhibiting no/low microsatellite instability, patients with distal colon and rectal cancers experienced lower mortality, regardless of microsatellite instability status; patients with proximal colon cancer exhibiting high microsatellite instability had the lowest mortality. Study limitations include the absence of stage at diagnosis and cause-of-death information for all but a subset of study participants. Some patient groups defined jointly by tumor site and microsatellite instability status are subject to small numbers. Proximal colon cancer survival differs from survival for distal colon and rectal cancer in a manner apparently dependent on microsatellite instability status. These

TGFBR2 and BAX mononucleotide tract mutations, microsatellite instability, and prognosis in 1072 colorectal cancers.

Directory of Open Access Journals (Sweden)

Kaori Shima

Full Text Available Mononucleotide tracts in the coding regions of the TGFBR2 and BAX genes are commonly mutated in microsatellite instability-high (MSI-high colon cancers. The receptor TGFBR2 plays an important role in the TGFB1 (transforming growth factor-β, TGF-β signaling pathway, and BAX plays a key role in apoptosis. However, a role of TGFBR2 or BAX mononucleotide mutation in colorectal cancer as a prognostic biomarker remains uncertain.We utilized a database of 1072 rectal and colon cancers in two prospective cohort studies (the Nurses' Health Study and the Health Professionals Follow-up Study. Cox proportional hazards model was used to compute mortality hazard ratio (HR, adjusted for clinical, pathological and molecular features including the CpG island methylator phenotype (CIMP, LINE-1 methylation, and KRAS, BRAF and PIK3CA mutations. MSI-high was observed in 15% (162/1072 of all colorectal cancers. TGFBR2 and BAX mononucleotide mutations were detected in 74% (117/159 and 30% (48/158 of MSI-high tumors, respectively. In Kaplan-Meier analysis as well as univariate and multivariate Cox regression analyses, compared to microsatellite stable (MSS/MSI-low cases, MSI-high cases were associated with superior colorectal cancer-specific survival [adjusted HR, 0.34; 95% confidence interval (CI, 0.20-0.57] regardless of TGFBR2 or BAX mutation status. Among MSI-high tumors, TGFBR2 mononucleotide mutation was associated with CIMP-high independent of other variables [multivariate odds ratio, 3.57; 95% CI, 1.66-7.66; p = 0.0011].TGFBR2 or BAX mononucleotide mutations are not associated with the patient survival outcome in MSI-high colorectal cancer. Our data do not support those mutations as prognostic biomarkers (beyond MSI in colorectal carcinoma.

A Mononucleotide Markers Panel to Identify hMLH1/hMSH2 Germline Mutations

Directory of Open Access Journals (Sweden)

M. Pedroni

2007-01-01

Full Text Available Hereditary NonPolyposis Colorectal Cancer (Lynch syndrome is an autosomal dominant disease caused by germline mutations in a class of genes deputed to maintain genomic integrity during cell replication, mutations result in a generalized genomic instability, particularly evident at microsatellite loci (Microsatellite Instability, MSI. MSI is present in 85–90% of colorectal cancers that occur in Lynch Syndrome. To standardize the molecular diagnosis of MSI, a panel of 5 microsatellite markers was proposed (known as the “Bethesda panel”. Aim of our study is to evaluate if MSI testing with two mononucleotide markers, such as BAT25 and BAT26, was sufficient to identify patients with hMLH1/hMSH2 germline mutations. We tested 105 tumours for MSI using both the Bethesda markers and the two mononucleotide markers BAT25 and BAT26. Moreover, immunohistochemical evaluation of MLH1 and MSH2 proteins was executed on the tumours with at least one unstable microsatellite, whereas germline hMLH1/hMSH2 mutations were searched for all cases showing two or more unstable microsatellites.

Synthesis and biological evaluation of 6H-1-benzopyrano[4,3-b]quinolin-6-one derivatives as inhibitors of colon cancer cell growth

Directory of Open Access Journals (Sweden)

Tie-Ling Li

2015-08-01

Full Text Available A convenient synthesis of 6H-1-benzopyrano[4,3-b]quinolin-6-one derivatives was reported using 4-chloro-2-oxo-2H-chromene-3-carbaldehyde with different aromatic amines using silica sulfuric acid. The compounds were tested for their anticancer activity against colon (HCT-116 and S1-MI-80, prostate (PC3 and DU-145, breast (MCF-7 and MDAMB-231 cancer cells. These com-pounds showed more selectivity and potent cytotoxic activity against colon cancer cells. 3c was tested against five other colon cancer cell lines (HT-29, HCT-15, LS-180, LS-174, and LoVo, which had similar cytotoxicity and selectivity. 3c did not induce PXR-regulated ABCB1 or ABCG2 transporters. In fact, 3c induced cytotoxicity in HEK293 cells over expressing ABCB1 or ABCG2 to the same extent as in normal HEK293 cells. It was cytotoxic approximately 3- and 5-fold to resistant colon carcinoma S1-MI-80 cells. 3c also produced concentration-dependent changes in HCT-116 colon cancer cells, in mitochondrial membrane potential, leading to apoptosis, and sub-micromolar concentrations caused chromosomal DNA fragmentation.

Outcomes of colon resection in patients with metastatic colon cancer.

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Moghadamyeghaneh, Zhobin; Hanna, Mark H; Hwang, Grace; Mills, Steven; Pigazzi, Alessio; Stamos, Michael J; Carmichael, Joseph C

2016-08-01

Patients with advanced colorectal cancer have a high incidence of postoperative complications. We sought to identify outcomes of patients who underwent resection for colon cancer by cancer stage. The National Surgical Quality Improvement Program database was used to evaluate all patients who underwent colon resection with a diagnosis of colon cancer from 2012 to 2014. Multivariate logistic regression analysis was performed to investigate patient outcomes by cancer stage. A total of 7,786 colon cancer patients who underwent colon resection were identified. Of these, 10.8% had metastasis at the time of operation. Patients with metastatic disease had significantly increased risks of perioperative morbidity (adjusted odds ratio [AOR]: 1.44, P = .01) and mortality (AOR: 3.72, P = .01). Patients with metastatic disease were significantly younger (AOR: .99, P colon cancer have metastatic disease. Postoperative morbidity and mortality are significantly higher than in patients with localized disease. Published by Elsevier Inc.

FXR silencing in human colon cancer by DNA methylation and KRAS signaling.

Science.gov (United States)

Bailey, Ann M; Zhan, Le; Maru, Dipen; Shureiqi, Imad; Pickering, Curtis R; Kiriakova, Galina; Izzo, Julie; He, Nan; Wei, Caimiao; Baladandayuthapani, Veerabhadran; Liang, Han; Kopetz, Scott; Powis, Garth; Guo, Grace L

2014-01-01

Farnesoid X receptor (FXR) is a bile acid nuclear receptor described through mouse knockout studies as a tumor suppressor for the development of colon adenocarcinomas. This study investigates the regulation of FXR in the development of human colon cancer. We used immunohistochemistry of FXR in normal tissue (n = 238), polyps (n = 32), and adenocarcinomas, staged I-IV (n = 43, 39, 68, and 9), of the colon; RT-quantitative PCR, reverse-phase protein array, and Western blot analysis in 15 colon cancer cell lines; NR1H4 promoter methylation and mRNA expression in colon cancer samples from The Cancer Genome Atlas; DNA methyltransferase inhibition; methyl-DNA immunoprecipitation (MeDIP); bisulfite sequencing; and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) knockdown assessment to investigate FXR regulation in colon cancer development. Immunohistochemistry and quantitative RT-PCR revealed that expression and function of FXR was reduced in precancerous lesions and silenced in a majority of stage I-IV tumors. FXR expression negatively correlated with phosphatidylinositol-4, 5-bisphosphate 3 kinase signaling and the epithelial-to-mesenchymal transition. The NR1H4 promoter is methylated in ~12% colon cancer The Cancer Genome Atlas samples, and methylation patterns segregate with tumor subtypes. Inhibition of DNA methylation and KRAS silencing both increased FXR expression. FXR expression is decreased early in human colon cancer progression, and both DNA methylation and KRAS signaling may be contributing factors to FXR silencing. FXR potentially suppresses epithelial-to-mesenchymal transition and other oncogenic signaling cascades, and restoration of FXR activity, by blocking silencing mechanisms or increasing residual FXR activity, represents promising therapeutic options for the treatment of colon cancer.

Vasohibin-1 suppresses colon cancer

OpenAIRE

Liu, Shuai; Han, Bing; Zhang, Qunyuan; Dou, Jie; Wang, Fang; Lin, Wenli; Sun, Yuping; Peng, Guangyong

2015-01-01

Vasohibin-1 (VASH1) is an endogenous angiogenesis inhibitor. However, the clinical relevance of VASH1 in colon cancer and its regulations on cancer angiogenesis and cancer cell biological characteristics are still unknown. Here we showed that stromal VASH1 levels were negatively correlated with tumor size, advanced clinical stage and distant metastases in colon cancer patients. Overexpression of VASH1 in colon cancer cells induced apoptosis and senescence, inhibiting cancer cell growth and co...

Colorectal carcinomas with microsatellite instability display a different pattern of target gene mutations according to large bowel site of origin

International Nuclear Information System (INIS)

Pinheiro, Manuela; Fragoso, Maria; Santos, Lúcio; Henrique, Rui; Lopes, Paula; Lopes, Carlos; Lothe, Ragnhild A; Teixeira, Manuel R; Ahlquist, Terje; Danielsen, Stine A; Lind, Guro E; Veiga, Isabel; Pinto, Carla; Costa, Vera; Afonso, Luís; Sousa, Olga

2010-01-01

Only a few studies have addressed the molecular pathways specifically involved in carcinogenesis of the distal colon and rectum. We aimed to identify potential differences among genetic alterations in distal colon and rectal carcinomas as compared to cancers arising elsewhere in the large bowel. Constitutional and tumor DNA from a test series of 37 patients with rectal and 25 patients with sigmoid carcinomas, previously analyzed for microsatellite instability (MSI), was studied for BAX, IGF2R, TGFBR2, MSH3, and MSH6 microsatellite sequence alterations, BRAF and KRAS mutations, and MLH1 promoter methylation. The findings were then compared with those of an independent validation series consisting of 36 MSI-H carcinomas with origin from each of the large bowel regions. Immunohistochemical and germline mutation analyses of the mismatch repair system were performed when appropriate. In the test series, IGFR2 and BAX mutations were present in one and two out of the six distal MSI-H carcinomas, respectively, and no mutations were detected in TGFBR2, MSH3, and MSH6. We confirmed these findings in the validation series, with TGFBR2 and MSH3 microsatellite mutations occurring less frequently in MSI-H rectal and sigmoid carcinomas than in MSI-H colon carcinomas elsewhere (P = 0.00005 and P = 0.0000005, respectively, when considering all MSI-carcinomas of both series). No MLH1 promoter methylation was observed in the MSI-H rectal and sigmoid carcinomas of both series, as compared to 53% found in MSI-H carcinomas from other locations (P = 0.004). KRAS and BRAF mutational frequencies were 19% and 43% in proximal carcinomas and 25% and 17% in rectal/sigmoid carcinomas, respectively. The mechanism and the pattern of genetic changes driving MSI-H carcinogenesis in distal colon and rectum appears to differ from that occurring elsewhere in the colon and further investigation is warranted both in patients with sporadic or hereditary disease

Aspirin exerts high anti-cancer activity in PIK3CA-mutant colon cancer cells.

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Gu, Mancang; Nishihara, Reiko; Chen, Yang; Li, Wanwan; Shi, Yan; Masugi, Yohei; Hamada, Tsuyoshi; Kosumi, Keisuke; Liu, Li; da Silva, Annacarolina; Nowak, Jonathan A; Twombly, Tyler; Du, Chunxia; Koh, Hideo; Li, Wenbin; Meyerhardt, Jeffrey A; Wolpin, Brian M; Giannakis, Marios; Aguirre, Andrew J; Bass, Adam J; Drew, David A; Chan, Andrew T; Fuchs, Charles S; Qian, Zhi Rong; Ogino, Shuji

2017-10-20

Evidence suggests that nonsteroidal anti-inflammatory drug aspirin (acetylsalicylic acid) may improve patient survival in PIK3CA -mutant colorectal carcinoma, but not in PIK3CA -wild-type carcinoma. However, whether aspirin directly influences the viability of PIK3CA -mutant colon cancer cells is poorly understood. We conducted in vitro experiments to test our hypothesis that the anti-proliferative activity of aspirin might be stronger for PIK3CA -mutant colon cancer cells than for PIK3CA -wild-type colon cancer cells. We measured the anti-proliferative effect of aspirin at physiologic concentrations in seven PIK3CA -mutant and six PIK3CA -wild-type human colon cancer cell lines. After exposure to aspirin, the apoptotic index and cell cycle phase of colon cancer cells were assessed. In addition, the effect of aspirin was examined in parental SW48 cells and SW48 cell clones with individual knock-in PIK3CA mutations of either c.3140A>G (p.H1047R) or c.1633G>A (p.E545K). Aspirin induced greater dose-dependent loss of cell viability in PIK3CA -mutant cells than in PIK3CA -wild-type cells after treatment for 48 and 72 hours. Aspirin treatment also led to higher proportions of apoptotic cells and G0/G1 phase arrest in PIK3CA -mutant cells than in PIK3CA -wild-type cells. Aspirin treatment of isogenic SW48 cells carrying a PIK3CA mutation, either c.3140A>G (p.H1047R) or c.1633G>A (p. E545K), resulted in a more significant loss of cell viability compared to wild-type controls. Our findings indicate that aspirin causes cell cycle arrest, induces apoptosis, and leads to loss of cell viability more profoundly in PIK3CA -mutated colon cancer cells than in PIK3CA -wild-type colon cancer cells. These findings support the use of aspirin to treat patients with PIK3CA -mutant colon cancer.

The benefit of microsatellite instability is attenuated by chemotherapy in stage II and stage III gastric cancer: Results from a large cohort with subgroup analyses.

Science.gov (United States)

Kim, Soo Young; Choi, Yoon Young; An, Ji Yeong; Shin, Hyun Beak; Jo, Ara; Choi, Hyeji; Seo, Sang Hyuk; Bang, Hui-Jae; Cheong, Jae-Ho; Hyung, Woo Jin; Noh, Sung Hoon

2015-08-15

We previously reported that the prognosis of microsatellite instability high (MSI-H) gastric cancer is similar to that of MSI-low/microsatellite stable (MSI-L/MSS) gastric cancer. The reason for this seemed to be related to the effects of chemotherapy. To verify this hypothesis, we expanded the study population and reanalyzed the prognosis of MSI-H gastric cancer. Data from 1,276 patients with Stage II and III gastric cancer who underwent gastrectomy with curative intent between January 2005 and June 2010 were reviewed. The prognosis of MSI-H tumors in comparison with MSI-L/MSS tumors was analyzed, according to the administration of chemotherapy and other clinicopathologic features. A total of 361 (28.3%) patients did not receive chemotherapy (MSI-H = 47 and MSI-L/MSS = 314), whereas 915 (71.7%) patients did receive chemotherapy (MSI-H = 58 and MSI-L/MSS = 857). The hazard ratio of MSI-H versus MSI-L/MSS was 0.49 (95% confidence interval: 0.26-0.94, p = 0.031) when chemotherapy was not received and 1.16 (95% confidence interval: 0.78-1.71, p = 0.466) when chemotherapy was received. In subgroup analyses, the prognosis of MSI-H was better in Stage III, women, with lymph node metastasis, and undifferentiated histology subgroups when chemotherapy was not received. However, in patients treated with chemotherapy, prognosis was worse for MSI-H tumors in Stage III, undifferentiated histology, and diffuse type subgroups of gastric cancer. In conclusion, MSI-H tumors were associated with a good prognosis in Stage II and III gastric cancer when patients were treated by surgery alone, and the benefits of MSI-H status were attenuated by chemotherapy. © 2015 UICC.

Carotenoids and colon cancer.

Science.gov (United States)

Slattery, M L; Benson, J; Curtin, K; Ma, K N; Schaeffer, D; Potter, J D

2000-02-01

Carotenoids have numerous biological properties that may underpin a role for them as chemopreventive agents. However, except for beta-carotene, little is known about how dietary carotenoids are associated with common cancers, including colon cancer. The objective of this study was to evaluate associations between dietary alpha-carotene, beta-carotene, lycopene, lutein, zeaxanthin, and beta-cryptoxanthin and the risk of colon cancer. Data were collected from 1993 case subjects with first primary incident adenocarcinoma of the colon and from 2410 population-based control subjects. Dietary data were collected from a detailed diet-history questionnaire and nutrient values for dietary carotenoids were obtained from the US Department of Agriculture-Nutrition Coordinating Center carotenoid database (1998 updated version). Lutein was inversely associated with colon cancer in both men and women [odds ratio (OR) for upper quintile of intake relative to lowest quintile of intake: 0.83; 95% CI: 0.66, 1.04; P = 0.04 for linear trend]. The greatest inverse association was observed among subjects in whom colon cancer was diagnosed when they were young (OR: 0.66; 95% CI: 0.48, 0.92; P = 0.02 for linear trend) and among those with tumors located in the proximal segment of the colon (OR: 0.65; 95% CI: 0.51, 0.91; P lettuce, tomatoes, oranges and orange juice, carrots, celery, and greens. These data suggest that incorporating these foods into the diet may help reduce the risk of developing colon cancer.

Classification and risk assessment of individuals with familial polyposis, Gardner's syndrome, and familial non-polyposis colon cancer from [3H]thymidine labeling patterns in colonic epithelial cells

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Lipkin, M.; Blattner, W.A.; Gardner, E.J.; Burt, R.W.; Lynch, H.; Deschner, E.; Winawer, S.; Fraumeni, J.F. Jr.

1984-01-01

A probabilistic analysis has been developed to assist the binary classification and risk assessment of members of familial colon cancer kindreds. The analysis is based on the microautoradiographic observation of [ 3 H]thymidine-labeled epithelial cells in colonic mucosa of the kindred members. From biopsies of colonic mucosa which are labeled with [ 3 H]thymidine in vitro, the degree of similarity of each subject's cell-labeling pattern measured over entire crypts was automatically compared to the labeling patterns of high-risk and low-risk reference populations. Each individual was then presumptively classified and assigned to one of the reference populations, and a degree of risk for the classification was provided. In carrying out the analysis, a linear score was calculated for each individual relative to each of the reference populations, and the classification was based on the polarity of the score difference; the degree of risk was then quantitated from the magnitude of the score difference. When the method was applied to kindreds having either familial polyposis or familial non-polyposis colon cancer, it effectively segregated individuals affected with disease from others at low risk, with sensitivity and specificity ranging from 71 to 92%. Further application of the method to asymptomatic family members believed to be at 50% risk on the basis of pedigree evaluation revealed a biomodal distribution to nearly zero or full risk. The accuracy and simplicity of this approach and its capability of revealing early stages of abnormal colonic epithelial cell development indicate potential for preclinical screening of subjects at risk in cancer-prone kindreds and for assisting the analysis of modes of inheritance

Muscarinic Receptor Signaling in Colon Cancer

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Rosenvinge, Erik C. von, E-mail: evonrose@medicine.umaryland.edu; Raufman, Jean-Pierre [University of Maryland School of Medicine, Division of Gastroenterology & Hepatology, 22 S. Greene Street, N3W62, Baltimore, MD 21201 (United States); Department of Veterans Affairs, VA Maryland Health Care System, 10 North Greene Street, Baltimore, MD 21201 (United States)

2011-03-02

According to the adenoma-carcinoma sequence, colon cancer results from accumulating somatic gene mutations; environmental growth factors accelerate and augment this process. For example, diets rich in meat and fat increase fecal bile acids and colon cancer risk. In rodent cancer models, increased fecal bile acids promote colon dysplasia. Conversely, in rodents and in persons with inflammatory bowel disease, low-dose ursodeoxycholic acid treatment alters fecal bile acid composition and attenuates colon neoplasia. In the course of elucidating the mechanism underlying these actions, we discovered that bile acids interact functionally with intestinal muscarinic receptors. The present communication reviews muscarinic receptor expression in normal and neoplastic colon epithelium, the role of autocrine signaling following synthesis and release of acetylcholine from colon cancer cells, post-muscarinic receptor signaling including the role of transactivation of epidermal growth factor receptors and activation of the ERK and PI3K/AKT signaling pathways, the structural biology and metabolism of bile acids and evidence for functional interaction of bile acids with muscarinic receptors on human colon cancer cells. In murine colon cancer models, deficiency of subtype 3 muscarinic receptors attenuates intestinal neoplasia; a proof-of-concept supporting muscarinic receptor signaling as a therapeutic target for colon cancer.

Muscarinic Receptor Signaling in Colon Cancer

International Nuclear Information System (INIS)

Rosenvinge, Erik C. von; Raufman, Jean-Pierre

2011-01-01

According to the adenoma-carcinoma sequence, colon cancer results from accumulating somatic gene mutations; environmental growth factors accelerate and augment this process. For example, diets rich in meat and fat increase fecal bile acids and colon cancer risk. In rodent cancer models, increased fecal bile acids promote colon dysplasia. Conversely, in rodents and in persons with inflammatory bowel disease, low-dose ursodeoxycholic acid treatment alters fecal bile acid composition and attenuates colon neoplasia. In the course of elucidating the mechanism underlying these actions, we discovered that bile acids interact functionally with intestinal muscarinic receptors. The present communication reviews muscarinic receptor expression in normal and neoplastic colon epithelium, the role of autocrine signaling following synthesis and release of acetylcholine from colon cancer cells, post-muscarinic receptor signaling including the role of transactivation of epidermal growth factor receptors and activation of the ERK and PI3K/AKT signaling pathways, the structural biology and metabolism of bile acids and evidence for functional interaction of bile acids with muscarinic receptors on human colon cancer cells. In murine colon cancer models, deficiency of subtype 3 muscarinic receptors attenuates intestinal neoplasia; a proof-of-concept supporting muscarinic receptor signaling as a therapeutic target for colon cancer

Muscarinic Receptor Signaling in Colon Cancer

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Jean-Pierre Raufman

2011-03-01

Full Text Available According to the adenoma-carcinoma sequence, colon cancer results from accumulating somatic gene mutations; environmental growth factors accelerate and augment this process. For example, diets rich in meat and fat increase fecal bile acids and colon cancer risk. In rodent cancer models, increased fecal bile acids promote colon dysplasia. Conversely, in rodents and in persons with inflammatory bowel disease, low-dose ursodeoxycholic acid treatment alters fecal bile acid composition and attenuates colon neoplasia. In the course of elucidating the mechanism underlying these actions, we discovered that bile acids interact functionally with intestinal muscarinic receptors. The present communication reviews muscarinic receptor expression in normal and neoplastic colon epithelium, the role of autocrine signaling following synthesis and release of acetylcholine from colon cancer cells, post-muscarinic receptor signaling including the role of transactivation of epidermal growth factor receptors and activation of the ERK and PI3K/AKT signaling pathways, the structural biology and metabolism of bile acids and evidence for functional interaction of bile acids with muscarinic receptors on human colon cancer cells. In murine colon cancer models, deficiency of subtype 3 muscarinic receptors attenuates intestinal neoplasia; a proof-of-concept supporting muscarinic receptor signaling as a therapeutic target for colon cancer.

Molecular subtypes in stage II-III colon cancer defined by genomic instability: early recurrence-risk associated with a high copy-number variation and loss of RUNX3 and CDKN2A.

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Marianne Berg

Full Text Available We sought to investigate various molecular subtypes defined by genomic instability that may be related to early death and recurrence in colon cancer.We sought to investigate various molecular subtypes defined by instability at microsatellites (MSI, changes in methylation patterns (CpG island methylator phenotype, CIMP or copy number variation (CNV in 8 genes. Stage II-III colon cancers (n = 64 were investigated by methylation-specific multiplex ligated probe amplification (MS-MLPA. Correlation of CNV, CIMP and MSI, with mutations in KRAS and BRAFV600E were assessed for overlap in molecular subtypes and early recurrence risk by uni- and multivariate regression.The CIMP phenotype occurred in 34% (22/64 and MSI in 27% (16/60 of the tumors, with noted CIMP/MSI overlap. Among the molecular subtypes, a high CNV phenotype had an associated odds ratio (OR for recurrence of 3.2 (95% CI 1.1-9.3; P = 0.026. Losses of CACNA1G (OR of 2.9, 95% CI 1.4-6.0; P = 0.001, IGF2 (OR of 4.3, 95% CI 1.1-15.8; P = 0.007, CDKN2A (p16 (OR of 2.0, 95% CI 1.1-3.6; P = 0.024, and RUNX3 (OR of 3.4, 95% CI 1.3-8.7; P = 0.002 were associated with early recurrence, while MSI, CIMP, KRAS or BRAF V600E mutations were not. The CNV was significantly higher in deceased patients (CNV in 6 of 8 compared to survivors (CNV in 3 of 8. Only stage and loss of RUNX3 and CDKN2A were significant in the multivariable risk-model for early recurrence.A high copy number variation phenotype is a strong predictor of early recurrence and death, and may indicate a dose-dependent relationship between genetic instability and outcome. Loss of tumor suppressors RUNX3 and CDKN2A were related to recurrence-risk and warrants further investigation.

Cathelicidin suppresses colon cancer development by inhibition of cancer associated fibroblasts

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Cheng M

2014-12-01

Full Text Available Michelle Cheng,1,* Samantha Ho,1,* Jun Hwan Yoo,1,2,* Deanna Hoang-Yen Tran,1,* Kyriaki Bakirtzi,1 Bowei Su,1 Diana Hoang-Ngoc Tran,1 Yuzu Kubota,1 Ryan Ichikawa,1 Hon Wai Koon1 1Center for Inflammatory Bowel Diseases, Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA; 2Digestive Disease Center, CHA University Bundang Medical Center, Seongnam, Republic of Korea *These authors share co-first authorship Background: Cathelicidin (LL-37 in humans and mCRAMP in mice represents a family of endogenous antimicrobial and anti-inflammatory peptides. Cancer-associated fibroblasts can promote the proliferation of colon cancer cells and growth of colon cancer tumors. Methods: We examined the role of cathelicidin in the development of colon cancer, using subcutaneous human HT-29 colon-cancer-cell-derived tumor model in nude mice and azoxymethane- and dextran sulfate-mediated colon cancer model in C57BL/6 mice. We also determined the indirect antitumoral mechanism of cathelicidin via the inhibition of epithelial–mesenchymal transition (EMT of colon cancer cells and fibroblast-supported colon cancer cell proliferation. Results: Intravenous administration of cathelicidin expressing adeno-associated virus significantly reduced the size of tumors, tumor-derived collagen expression, and tumor-derived fibroblast expression in HT-29-derived subcutaneous tumors in nude mice. Enema administration of the mouse cathelicidin peptide significantly reduced the size and number of colonic tumors in azoxymethane- and dextran sulfate-treated mice without inducing apoptosis in tumors and the adjacent normal colonic tissues. Cathelicidin inhibited the collagen expression and vimentin-positive fibroblast expression in colonic tumors. Cathelicidin did not directly affect HT-29 cell viability, but did significantly reduce tumor growth factor-ß1-induced EMT of colon cancer cells. Media conditioned by the

Vasohibin-1 suppresses colon cancer

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Liu, Shuai; Han, Bing; Zhang, Qunyuan; Dou, Jie; Wang, Fang; Lin, Wenli; Sun, Yuping; Peng, Guangyong

2015-01-01

Vasohibin-1 (VASH1) is an endogenous angiogenesis inhibitor. However, the clinical relevance of VASH1 in colon cancer and its regulations on cancer angiogenesis and cancer cell biological characteristics are still unknown. Here we showed that stromal VASH1 levels were negatively correlated with tumor size, advanced clinical stage and distant metastases in colon cancer patients. Overexpression of VASH1 in colon cancer cells induced apoptosis and senescence, inhibiting cancer cell growth and colony formation in vitro and tumor growth in vivo. In addition, knockdown of VASH1 in cancer cells promoted cell growth, adhesion and migration in vitro, and enhanced tumorigenesis and metastasis in vivo. PMID:25797264

Vasohibin-1 suppresses colon cancer.

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Liu, Shuai; Han, Bing; Zhang, Qunyuan; Dou, Jie; Wang, Fang; Lin, Wenli; Sun, Yuping; Peng, Guangyong

2015-04-10

Vasohibin-1 (VASH1) is an endogenous angiogenesis inhibitor.However, the clinical relevance of VASH1 in colon cancer and its regulations on cancer angiogenesis and cancer cell biological characteristics are still unknown. Here we showed that stromal VASH1 levels were negatively correlated with tumor size, advanced clinical stage and distant metastases in colon cancer patients. Overexpression of VASH1 in colon cancer cells induced apoptosis and senescence, inhibiting cancer cell growth and colony formation in vitro and tumor growth in vivo. In addition, knockdown of VASH1 in cancer cells promoted cell growth, adhesion and migration in vitro, and enhanced tumorigenesis and metastasis in vivo.

Colon cancer proliferating desulfosinigrin in wasabi (Wasabia japonica).

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Weil, Marvin J; Zhang, Yanjun; Nair, Muraleedharan G

2004-01-01

A reduced incidence of different types of cancer has been linked to consumption of Brassica vegetables, and there is evidence that glucosinolates (GSLs) and their hydrolysis products play a role in reducing cancer risk. Wasabi (Wasabia japonica) and horseradish (Armoracia rusticana), both Brassica vegetables, are widely used condiments both in Japanese cuisine and in the United States. Desulfosinigrin (DSS) (1) was isolated from a commercially available wasabi powder and from fresh wasabi roots. Sinigrin (2) was isolated from horseradish roots. DSS and sinigrin were evaluated for their inhibitory effects on cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes, on lipid peroxidation, and on the proliferation of human colon (HCT-116), breast (MCF-7), lung (NCIH460), and central nervous system (CNS, SF-268) cancer cell lines. DSS did not inhibit COX enzymes or lipid peroxidation at 250 microg/ml. Sinigrin inhibited lipid peroxidation by 71% at 250 microg/ml. However, DSS promoted the growth of HCT-116 (colon) and NCI H460 (lung) human cancer cells as determined by the MTT assay in a concentration-dependent manner. At 3.72 microg/ml, a 27% increase in the number of viable human HCT-116 colon cancer cells was observed; the corresponding increases at 7.50 and 15 microg/ml were 42 and 69%, respectively. At 60 microg/ml, DSS doubled the number of HCT-16 colon cancer cells. For NCI H460 human lung cancer cells, DSS at 60 microg/ml increased the cell number by 20%. Sinigrin showed no proliferating effect on the tumor cells tested. This is the first report of the tumor cell-proliferating activity by a desulfoglucosinolate, the biosynthetic precursor of GSLs found in Brassica spp.

The nonfermentable dietary fiber lignin alters putative colon cancer risk factors but does not protect against DMH-induced colon cancer in rats.

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Cameron, I L; Hardman, W E; Heitman, D W

1997-01-01

The effect of supplementation of the diet with autohydrolyzed lignin on 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis was studied using 112 male Sprague-Dawley rats. Rats received eight weekly injections of DMH (9.5 mg/kg s.c.) or the saline vehicle solution and then were maintained on a basal AIN-76 fiber-free diet or the basal fiber-free diet plus 5% or 10% (wt/wt) lignin for 24 weeks. Rats were killed 32 weeks after the start of the experiment. Colon tumor incidence, location, and multiplicity were determined. Body weight, caloric intake, fecal dry weight, gut transit time, pH of cecal contents, and total fecal bile acid excretion were measured. Supplementation of the diet with 5% or 10% lignin resulted in increased fecal dry weight and total fecal bile acid excretion and in decreased gut transit time, colon pH, and fecal bile acid concentration. Dietary lignin did not significantly affect colon tumor incidence or multiplicity compared with the fiber-free diet. Thus dietary supplementation with autohydrolyzed lignin, a food fiber with good bulking characteristics, had a significant effect on several factors that have previously been linked to reduction of colon cancer risk, but the consumption of high levels of lignin did not decrease the risk for colon cancer.

PET-MRI in Diagnosing Patients With Colon or Rectal Cancer

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2015-11-25

Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage IIA Colon Cancer; Stage IIA Rectal Cancer; Stage IIB Colon Cancer; Stage IIB Rectal Cancer; Stage IIC Colon Cancer; Stage IIC Rectal Cancer; Stage IIIA Colon Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

Use of nonsteroidal antiinflamatory drugs for chemoprevention of colon cancer

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Milić Aleksandra

2013-01-01

Full Text Available Colorectal cancer is in the third most frequent cancer among malignant tumors of both sexes in developed countries. It is predominantly a disease of older persons and occurs mostly after the age of 60. Although the etiology of colon cancer is unknown, it is assumed to arise as a result of unclear and complex interactions between genetic and environmental factors. The main element in the etiology of colorectal cancer is the process of genetic changes in epithelial cells of colon mucosa. It is believed that specific epidemiological factors such as stress, hypoxia, reduced intake of glucose and other nutrients, a hereditary predisposition to mutagenic effects, the meat in the diet, bile acids, reduced intake of minerals and vitamins as well as changes in pH of feces lead to initiation of the process of carcinogenesis in mucosa of the colon. Cancer chemoprevention is defined as the use of chemical agents in order to block, prevent or delay the reversal development or progress of cancer. It is believed that chemoprevention is a key component of cancer control, and numerous studies indicate potential role of NSAIDs in chemoprevention of colon cancer.

A Metabolic Study on Colon Cancer Using 1H Nuclear Magnetic Resonance Spectroscopy

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Zahra Zamani

2014-01-01

Full Text Available Background. Colorectal carcinoma is the third cause of cancer deaths in the world. For diagnosis, invasive methods like colonoscopy and sigmoidoscopy are used, and noninvasive screening tests are not very accurate. We decided to study the potential of 1HNMR spectroscopy with metabolomics and chemometrics as a preliminary noninvasive test. We obtained a distinguishing pattern of metabolites and metabolic pathways between colon cancer patient and normal. Methods. Sera were obtained from confirmed colon cancer patients and the same number of healthy controls. Samples were sent for 1HNMR spectroscopy and analysis was carried out Chenomex and MATLAB software. Metabolites were identified using Human Metabolic Data Base (HDMB and the main metabolic cycles were identified using Metaboanalyst software. Results. 15 metabolites were identified such as pyridoxine, orotidine, and taurocholic acid. Main metabolic cycles involved were the bile acid biosynthesis, vitamin B6 metabolism, methane metabolism, and glutathione metabolism. Discussion. The main detected metabolic cycles were also reported earlier in different cancers. Our observations corroborated earlier studies that suggest the importance of lowering serum LCA/DCA and increasing vitamin B6 intake to help prevent colon cancer. This work can be looked upon as a preliminary step in using 1HNMR analysis as a screening test before invasive procedures.

Colon cancer screening

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Screening for colon cancer; Colonoscopy - screening; Sigmoidoscopy - screening; Virtual colonoscopy - screening; Fecal immunochemical test; Stool DNA test; sDNA test; Colorectal cancer - screening; Rectal ...

Frondoside A Enhances the Anti-Cancer Effects of Oxaliplatin and 5-Fluorouracil on Colon Cancer Cells

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Samir Attoub

2018-05-01

Full Text Available Over recent years, we have demonstrated that Frondoside A, a triterpenoid glycoside isolated from an Atlantic sea cucumber, has potent in vitro and in vivo anti-cancer effects against human pancreatic, breast, and lung cancer. We have also demonstrated that Frondoside A is able to potentiate and/or synergize the anti-cancer effects of major classical cytotoxic agents, namely, gemcitabine, paclitaxel, and cisplatin, in the treatment of pancreatic, breast, and lung cancer, respectively. This study evaluates the impact of Frondoside A alone and in combination with the standard cytotoxic drugs oxaliplatin and 5-fluorouracil (5-FU in the treatment of colon cancer using three human colon cancer cell lines, namely, HT-29, HCT-116, and HCT8/S11. We demonstrate that Frondoside A, oxaliplatin, and 5-FU cause a concentration- and time-dependent reduction in the number of HT-29 colon cancer cells. A concentration of 2.5 µM of Frondoside A led to almost 100% inhibition of cell numbers at 72 h. A similar effect was only observed with a much higher concentration (100 µM of oxaliplatin or 5-FU. The reduction in cell numbers by Frondoside A, oxaliplatin, and 5-FU was also confirmed in two other colon cancer cell lines, namely, HCT8/S11 and HCT-116, treated for 48 h. The combinations of low concentrations of these drugs for 48 h in vitro clearly demonstrated that Frondoside A enhances the inhibition of cell numbers induced by oxaliplatin or 5-FU. Similarly, such a combination also efficiently inhibited colony growth in vitro. Interestingly, we found that the inhibition of ERK1/2 phosphorylation was significantly enhanced when Frondoside A was used in combination treatments. Moreover, we show that Frondoside A and 5-FU, when used alone, induce a concentration-dependent induction of apoptosis and that their pro-apoptotic effect is dramatically enhanced when used in combination. We further demonstrate that apoptosis induction upon the treatment of colon cancer

β-Catenin promotes colitis and colon cancer through imprinting of proinflammatory properties in T cells.

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Keerthivasan, Shilpa; Aghajani, Katayoun; Dose, Marei; Molinero, Luciana; Khan, Mohammad W; Venkateswaran, Vysak; Weber, Christopher; Emmanuel, Akinola Olumide; Sun, Tianjao; Bentrem, David J; Mulcahy, Mary; Keshavarzian, Ali; Ramos, Elena M; Blatner, Nichole; Khazaie, Khashayarsha; Gounari, Fotini

2014-02-26

The density and type of lymphocytes that infiltrate colon tumors are predictive of the clinical outcome of colon cancer. High densities of T helper 17 (T(H)17) cells and inflammation predict poor outcome, whereas infiltration by T regulatory cells (Tregs) that naturally suppress inflammation is associated with longer patient survival. However, the role of Tregs in cancer remains controversial. We recently reported that Tregs in colon cancer patients can become proinflammatory and tumor-promoting. These properties were directly linked with their expression of RORγt (retinoic acid-related orphan receptor-γt), the signature transcription factor of T(H)17 cells. We report that Wnt/β-catenin signaling in T cells promotes expression of RORγt. Expression of β-catenin was elevated in T cells, including Tregs, of patients with colon cancer. Genetically engineered activation of β-catenin in mouse T cells resulted in enhanced chromatin accessibility in the proximity of T cell factor-1 (Tcf-1) binding sites genome-wide, induced expression of T(H)17 signature genes including RORγt, and promoted T(H)17-mediated inflammation. Strikingly, the mice had inflammation of small intestine and colon and developed lesions indistinguishable from colitis-induced cancer. Activation of β-catenin only in Tregs was sufficient to produce inflammation and initiate cancer. On the basis of these findings, we conclude that activation of Wnt/β-catenin signaling in effector T cells and/or Tregs is causatively linked with the imprinting of proinflammatory properties and the promotion of colon cancer.

PKH26 staining defines distinct subsets of normal human colon epithelial cells at different maturation stages.

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Anna Pastò

Full Text Available BACKGROUND AND AIM: Colon crypts are characterized by a hierarchy of cells distributed along the crypt axis. Aim of this paper was to develop an in vitro system for separation of epithelial cell subsets in different maturation stages from normal human colon. METHODOLOGY AND MAJOR FINDINGS: Dissociated colonic epithelial cells were stained with PKH26, which allows identification of distinct populations based on their proliferation rate, and cultured in vitro in the absence of serum. The cytofluorimetric expression of CK20, Msi-1 and Lgr5 was studied. The mRNA levels of several stemness-associated genes were also compared in cultured cell populations and in three colon crypt populations isolated by microdissection. A PKH(pos population survived in culture and formed spheroids; this population included subsets with slow (PKH(high and rapid (PKH(low replicative rates. Molecular analysis revealed higher mRNA levels of both Msi-1 and Lgr-5 in PKH(high cells; by cytofluorimetric analysis, Msi-1(+/Lgr5(+ cells were only found within PKH(high cells, whereas Msi-1(+/Lgr5(- cells were also observed in the PKH(low population. As judged by qRT-PCR analysis, the expression of several stemness-associated markers (Bmi-1, EphB2, EpCAM, ALDH1 was highly enriched in Msi-1(+/Lgr5(+ cells. While CK20 expression was mainly found in PKH(low and PKH(neg cells, a small PKH(high subset co-expressed both CK20 and Msi-1, but not Lgr5; cells with these properties also expressed Mucin, and could be identified in vivo in colon crypts. These results mirrored those found in cells isolated from different crypt portions by microdissection, and based on proliferation rates and marker expression they allowed to define several subsets at different maturation stages: PKH(high/Lgr5(+/Msi-1(+/CK20(-, PKH(high/Lgr5(-/Msi-1(+/CK20(+, PKH(low/Lgr5(-/Msi-1(+/Ck20(-, and PKH(low/Lgr5(-/Msi-1(-/CK20(+ cells. CONCLUSIONS: Our data show the possibility of deriving in vitro, without any

Silencing of the hTERT gene by shRNA inhibits colon cancer SW480 cell growth in vitro and in vivo.

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Ai-Qun Liu

Full Text Available Human telomerase reverse transcriptase (hTERT is the key enzyme responsible for synthesizing and maintaining the telomeres on the ends of chromosomes, and it is essential for cell proliferation. This has made hTERT a focus of oncology research and an attractive target for anticancer drug development. In this study, we designed a small interfering RNA (siRNA targeting the catalytic subunit of hTERT and tested its effects on the growth of telomerase-positive human colon carcinoma SW480 cells in vitro, as well as on the tumorigenicity of these cells in nude mice. Transient and stable transfection of hTERT siRNA into colon cancer SW480 cells suppressed hTERT expression, reduced telomerase activity and inhibited cell growth and proliferation. Knocking down hTERT expression in SW480 tumors xenografted into nude mice significantly slowed tumor growth and promoted tumor cell apoptosis. Our results suggest that hTERT is involved in carcinogenesis of human colon carcinoma, and they highlight the therapeutic potential of a hTERT knock-down approach.

Nutrients and Risk of Colon Cancer

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Les Mery

2010-02-01

Full Text Available Dietary fats are thought to be important in the etiology of colon cancer. However, the evidence linking them is inconclusive. Studies on dietary protein, cholesterol and carbohydrate and the risk of colon cancer are also inconsistent. This study examined the association between dietary intake of protein, fats, cholesterol and carbohydrates, and the risk of colon cancer. Mailed questionnaires were completed by 1731 individuals with histologically confirmed cases of colon cancer and 3097 population controls between 1994 and 1997 in seven Canadian provinces. Measurements included socio-economic status, lifestyle habits and diet. A 69-item food frequency questionnaire was used to provide data on eating habits from two years before the study. Odds ratios (OR and 95% confidence intervals (CI were computed using unconditional logistic regression. The nutrients were categorized by quartiles based on the distributions among the controls. Intake of polyunsaturated fat, trans-fat and cholesterol were significantly associated with the risk of colon cancer; the ORs for the highest quartiles were 1.36 (95% CI, 1.02–1.80, 1.37 (95% CI, 1.10–1.71 and 1.42 (95% CI, 1.10–1.84, respectively. The association was stronger with proximal colon cancer (PCC. An increased risk was also observed with increasing intake of sucrose for both proximal and distal colon cancers; the ORs for the highest quartiles were 1.67 (95% CI, 1.22–2.29 for PCC and 1.58 (95% CI, 1.18–2.10 for distal colon cancer (DCC. An elevated risk of PCC was also found with increased lactose intake. Our findings provide evidence that a diet low in fat and sucrose could reduce the risk of various colon cancers.

Nutrients and Risk of Colon Cancer

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Hu, Jinfu, E-mail: Jinfu.hu@phac-aspc.gc.ca [Evidence and Risk Assessment Division, Centre for Chronic Disease Prevention and Control, Public Health Agency of Canada, 785 Carling Avenue, AL: 6807B, Ottawa, Ontario K1A 0K9 (Canada); La Vecchia, Carlo [Istituto di Ricerche Farmacologiche “Mario Negri,” Via La Masa, 19-20156 Milan (Italy); Istituto di Statistica Medica e Biometria, Università degli Studi di Milano, Via Venezian, 1, 20133 Milan (Italy); Negri, Eva [Istituto di Ricerche Farmacologiche “Mario Negri,” Via La Masa, 19-20156 Milan (Italy); Mery, Les [Evidence and Risk Assessment Division, Centre for Chronic Disease Prevention and Control, Public Health Agency of Canada, 785 Carling Avenue, AL: 6807B, Ottawa, Ontario K1A 0K9 (Canada)

2010-02-10

Dietary fats are thought to be important in the etiology of colon cancer. However, the evidence linking them is inconclusive. Studies on dietary protein, cholesterol and carbohydrate and the risk of colon cancer are also inconsistent. This study examined the association between dietary intake of protein, fats, cholesterol and carbohydrates, and the risk of colon cancer. Mailed questionnaires were completed by 1731 individuals with histologically confirmed cases of colon cancer and 3097 population controls between 1994 and 1997 in seven Canadian provinces. Measurements included socio-economic status, lifestyle habits and diet. A 69-item food frequency questionnaire was used to provide data on eating habits from two years before the study. Odds ratios (OR) and 95% confidence intervals (CI) were computed using unconditional logistic regression. The nutrients were categorized by quartiles based on the distributions among the controls. Intake of polyunsaturated fat, trans-fat and cholesterol were significantly associated with the risk of colon cancer; the ORs for the highest quartiles were 1.36 (95% CI, 1.02–1.80), 1.37 (95% CI, 1.10–1.71) and 1.42 (95% CI, 1.10–1.84), respectively. The association was stronger with proximal colon cancer (PCC). An increased risk was also observed with increasing intake of sucrose for both proximal and distal colon cancers; the ORs for the highest quartiles were 1.67 (95% CI, 1.22–2.29) for PCC and 1.58 (95% CI, 1.18–2.10) for distal colon cancer (DCC). An elevated risk of PCC was also found with increased lactose intake. Our findings provide evidence that a diet low in fat and sucrose could reduce the risk of various colon cancers.

Nutrients and Risk of Colon Cancer

International Nuclear Information System (INIS)

Hu, Jinfu; La Vecchia, Carlo; Negri, Eva; Mery, Les

2010-01-01

Dietary fats are thought to be important in the etiology of colon cancer. However, the evidence linking them is inconclusive. Studies on dietary protein, cholesterol and carbohydrate and the risk of colon cancer are also inconsistent. This study examined the association between dietary intake of protein, fats, cholesterol and carbohydrates, and the risk of colon cancer. Mailed questionnaires were completed by 1731 individuals with histologically confirmed cases of colon cancer and 3097 population controls between 1994 and 1997 in seven Canadian provinces. Measurements included socio-economic status, lifestyle habits and diet. A 69-item food frequency questionnaire was used to provide data on eating habits from two years before the study. Odds ratios (OR) and 95% confidence intervals (CI) were computed using unconditional logistic regression. The nutrients were categorized by quartiles based on the distributions among the controls. Intake of polyunsaturated fat, trans-fat and cholesterol were significantly associated with the risk of colon cancer; the ORs for the highest quartiles were 1.36 (95% CI, 1.02–1.80), 1.37 (95% CI, 1.10–1.71) and 1.42 (95% CI, 1.10–1.84), respectively. The association was stronger with proximal colon cancer (PCC). An increased risk was also observed with increasing intake of sucrose for both proximal and distal colon cancers; the ORs for the highest quartiles were 1.67 (95% CI, 1.22–2.29) for PCC and 1.58 (95% CI, 1.18–2.10) for distal colon cancer (DCC). An elevated risk of PCC was also found with increased lactose intake. Our findings provide evidence that a diet low in fat and sucrose could reduce the risk of various colon cancers

Clinical course and outcome of patients with high-level microsatellite instability cancers in a real-life setting: a retrospective analysis

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Halpern N

2017-03-01

Full Text Available Naama Halpern,1 Yael Goldberg,2 Luna Kadouri,2 Morasha Duvdevani,2 Tamar Hamburger,2 Tamar Peretz,2 Ayala Hubert2 1Institute of Oncology, The Chaim Sheba Medical Center, Tel Hashomer, Israel; 2Sharett Institute of Oncology, Hadassah Medical Center, Hebrew University, Jerusalem, Israel Background: The prognostic and predictive significance of the high-level microsatellite instability (MSI-H phenotype in various malignancies is unclear. We describe the characteristics, clinical course, and outcomes of patients with MSI-H malignancies treated in a real-life hospital setting.Patients and methods: A retrospective analysis of MSI-H cancer patient files was conducted. We analyzed the genetic data, clinical characteristics, and oncological treatments, including chemotherapy and surgical interventions.Results: Clinical data of 73 MSI-H cancer patients were available. Mean age at diagnosis of first malignancy was 52.3 years. Eight patients (11% had more than four malignancies each. Most patients (76% had colorectal cancer (CRC. Seventeen patients (23% had only extracolonic malignancies. Eighteen women (36% had gynecological malignancy. Nine women (18% had breast cancer. Mean follow-up was 8.5 years. Five-year overall survival and disease-free survival of all MSI-H cancer patients from first malignancy were 86% and 74.6%, respectively. Five-year overall survival rates of stage 2, 3, and 4 MSI-H CRC patients were 89.5%, 58.4%, and 22.9%, respectively.Conclusion: Although the overall prognosis of MSI-H cancer patients is favorable, this advantage may not be maintained in advanced MSI-H CRC patients. Keywords: microsatellite instability, malignancy, treatment, outcome

Curative resection of transverse colon cancer via minilaparotomy.

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Ishida, Hideyuki; Ishiguro, Tohru; Ishibashi, Keiichiro; Ohsawa, Tomonori; Okada, Norimichi; Kumamoto, Kensuke; Haga, Norihiro

2011-01-01

Minilaparotomy has been reported to be a minimally invasive alternative to laparoscopically assisted surgery. We retrospectively evaluated the usefulness of minilaparotomy for the resection of transverse colon cancer, which has generally been considered difficult to resect laparoscopically. Patients for whom curative resection was attempted for transverse colon cancer (n = 21) or sigmoid colon cancer (n = 81) via minilaparotomy (skin incision, transverse colon cancer as well as those with sigmoid colon cancer.

The significance of microsatellite instability in colorectal cancer after controlling for clinicopathological factors.

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Kang, Sanghee; Na, Younghyun; Joung, Sung Yup; Lee, Sun Il; Oh, Sang Cheul; Min, Byung Wook

2018-03-01

The colorectal cancer (CRC) patients with microsatellite instability (MSI) have distinct clinicopathological characteristics consisting of factors predicting positive and negative outcomes, such as a high lymph node harvest and poor differentiation. In this study, we measured the value of MSI as a prognostic factor after controlling for these discrepant factors. A total of 603 patients who underwent curative surgery for stages I to III colorectal cancer were enrolled. The patients were divided into microsatellite instability high (MSI-H) and microsatellite stable/microsatellite instability low (MSS/MSI-L) groups. Propensity score matching was used to match clinicopathological factors between the 2 groups. MSI-H patients had a high lymph node harvest (median: 31.0 vs 23.0, P controlling for pathological characteristics, MSI-H could be a potent prognostic factor regarding patient survival.

CALCIUM AND THE PREVENTION OF COLON CANCER

NARCIS (Netherlands)

WELBERG, JWM; KLEIBEUKER, JH; VANDERMEER, R; MULDER, NH; DEVRIES, EGE

1991-01-01

Diet is a major determinant of colon cancer risk. Calcium may protect against colon cancer, presumably by binding cytotoxic bile acids and fatty acids. Numerous studies support this proposition. In subjects at risk for colon cancer oral calcium supplementation has been shown to reduce rectal

Serum antibodies against frameshift peptides in microsatellite unstable colorectal cancer patients with Lynch syndrome.

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Reuschenbach, Miriam; Kloor, Matthias; Morak, Monika; Wentzensen, Nicolas; Germann, Anja; Garbe, Yvette; Tariverdian, Mirjam; Findeisen, Peter; Neumaier, Michael; Holinski-Feder, Elke; von Knebel Doeberitz, Magnus

2010-06-01

High level microsatellite instability (MSI-H) occurs in about 15% of colorectal cancer (CRCs), either as sporadic cancers or in the context of hereditary non-polyposis cancer or Lynch syndrome. In MSI-H CRC, mismatch repair deficiency leads to insertion/deletion mutations at coding microsatellites and thus to the translation of frameshift peptides (FSPs). FSPs are potent inductors of T cell responses in vitro and in vivo. The present study aims at the identification of FSP-specific humoral immune responses in MSI-H CRC and Lynch syndrome. Sera from patients with history of MSI-H CRC (n = 69), healthy Lynch syndrome mutation carriers (n = 31) and healthy controls (n = 52) were analyzed for antibodies against FSPs using peptide ELISA. Reactivities were measured against FSPs derived from genes frequently mutated in MSI-H CRCs, AIM2, TGFBR2, CASP5, TAF1B, ZNF294, and MARCKS. Antibody reactivity against FSPs was significantly higher in MSI-H CRC patients than in healthy controls (P = 0.036, Mann-Whitney) and highest in patients with shortest interval between tumor resection and serum sampling. Humoral immune responses in patients were most frequently directed against FSPs derived from mutated TAF1B (11.6%, 8/69) and TGFBR2 (10.1%, 7/69). Low level FSP-specific antibodies were also detected in healthy mutation carriers. Our results show that antibody responses against FSPs are detectable in MSI-H CRC patients and healthy Lynch syndrome mutation carriers. Based on the high number of defined FSP antigens, measuring FSP-specific humoral immune responses is a highly promising tool for future diagnostic application in MSI-H cancer patients.

Serum antibodies against frameshift peptides in microsatellite unstable colorectal cancer patients with Lynch syndrome

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Reuschenbach, Miriam; Kloor, Matthias; Morak, Monika; Wentzensen, Nicolas; Germann, Anja; Garbe, Yvette; Tariverdian, Mirjam; Findeisen, Peter; Neumaier, Michael; Holinski-Feder, Elke; Doeberitz, Magnus von Knebel

2014-01-01

High level microsatellite instability (MSI-H) occurs in about 15% of colorectal cancer (CRCs), either as sporadic cancers or in the context of hereditary non-polyposis cancer (HNPCC) or Lynch syndrome. In MSI-H CRC, mismatch repair deficiency leads to insertion/deletion mutations at coding microsatellites (cMS) and thus to the translation of frameshift peptides (FSPs). FSPs are potent inductors of T cell responses in vitro and in vivo. The present study aims at the identification of FSP-specific humoral immune responses in MSI-H CRC and Lynch syndrome. Sera from patients with history of MSI-H CRC (n=69), healthy Lynch syndrome mutation carriers (n=31) and healthy controls (n=52) were analyzed for antibodies against FSPs using peptide ELISA. Reactivities were measured against FSPs derived from genes frequently mutated in MSI-H CRCs, AIM2, TGFBR2, CASP5, TAF1B, ZNF294, and MARCKS. Antibody reactivity against FSPs was significantly higher in MSI-H CRC patients than in healthy controls (p=0.036, Mann-Whitney) and highest in patients with shortest interval between tumor resection and serum sampling. Humoral immune responses in patients were most frequently directed against FSPs derived from mutated TAF1B (11.6%, 8/69) and TGFBR2 (10.1%, 7/69). Low level FSP-specific antibodies were also detected in healthy mutation carriers. Our results show that antibody responses against FSPs are detectable in MSI-H CRC patients and healthy Lynch syndrome mutation carriers. Based on the high number of defined FSP antigens, measuring FSP-specific humoral immune responses is a highly promising tool for future diagnostic application in MSI-H cancer patients. PMID:19957108

Dietary patterns and colon cancer risk in Whites and African Americans in the North Carolina Colon Cancer Study.

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Satia, Jessie A; Tseng, Marilyn; Galanko, Joseph A; Martin, Christopher; Sandler, Robert S

2009-01-01

We examined associations of dietary patterns with colon cancer risk in African Americans and Whites from a case-control study in North Carolina. Incident colon cancer cases, 40 to 80 yr (n = 636), and matched controls (n = 1,042) were interviewed in person to elicit information on potential colon cancer risk factors. A validated food frequency questionnaire adapted to include regional foods captured diet over the year prior to diagnosis (cases) or interview date (controls). Three meaningful intake patterns were identified in both Whites and African Americans: "Western-Southern," "fruit-vegetable," and "metropolitan." Compared to the Western-Southern pattern, the fruit-vegetable and metropolitan patterns were associated with more healthful dietary behaviors (e.g., higher vegetable intake and lower red meat consumption), and demographic/lifestyle characteristics typically correlated with low colon cancer risk, for example, lower BMI, higher education, and higher NSAID use. The fruit-vegetable pattern was significantly inversely associated with colon cancer risk in Whites (OR = 0.4, 95% CI = 0.3-0.6) and the metropolitan pattern with a nonsignificant 30% risk reduction in both Whites and African Americans after adjustment for education. The Western-Southern pattern was not associated with colon cancer risk. These findings may explain some of the racial differences in colon cancer incidence and underscore the importance of examining diet-cancer associations in different population subgroups.

Increased colon cancer risk after severe Salmonella infection.

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Lapo Mughini-Gras

Full Text Available Colon cancer constitutes one of the most frequent malignancies. Previous studies showed that Salmonella manipulates host cell signaling pathways and that Salmonella Typhimurium infection facilitates colon cancer development in genetically predisposed mice. This epidemiological study examined whether severe Salmonella infection, usually acquired from contaminated food, is associated with increased colon cancer risk in humans.We performed a nationwide registry-based study to assess colon cancer risk after diagnosed Salmonella infection. National infectious disease surveillance records (1999-2015 for Dutch residents aged ≥20 years when diagnosed with salmonellosis (n = 14,264 were linked to the Netherlands Cancer Registry. Salmonella-infected patients were laboratory-confirmed under medical consultation after 1-2 weeks of illness. These datasets also contained information on Salmonella serovar and type of infection. Colon cancer risk (overall and per colon subsite among patients with a diagnosed Salmonella infection was compared with expected colon cancer risk in the general population. Data from the nationwide registry of histo- and cytopathology (PALGA and Statistics Netherlands (CBS allowed assessing potential effects of age, gender, latency, socioeconomic status, genetic predisposition, inflammatory bowel disease (IBD, and tumor features. We found that compared to the general population, colon cancer risk was significantly increased (standardized incidence ratio [SIR] 1.54; 95%CI 1.09-2.10 among patients with Salmonella infection diagnosed <60 years of age. Such increased risk concerned specifically the ascending/transverse colon (SIR 2.12; 95%CI 1.38-3.09 after S. Enteritidis infection (SIR 2.97; 95%CI 1.73-4.76. Salmonellosis occurred more frequently among colon cancer patients with pre-infectious IBD, a known risk factor for colon cancer. Colon tumors of patients with a history of Salmonella infection were mostly of low grade

Increased colon cancer risk after severe Salmonella infection

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Mooij, Sofie; Neefjes-Borst, E. Andra; van Pelt, Wilfrid; Neefjes, Jacques

2018-01-01

Background Colon cancer constitutes one of the most frequent malignancies. Previous studies showed that Salmonella manipulates host cell signaling pathways and that Salmonella Typhimurium infection facilitates colon cancer development in genetically predisposed mice. This epidemiological study examined whether severe Salmonella infection, usually acquired from contaminated food, is associated with increased colon cancer risk in humans. Methods and findings We performed a nationwide registry-based study to assess colon cancer risk after diagnosed Salmonella infection. National infectious disease surveillance records (1999–2015) for Dutch residents aged ≥20 years when diagnosed with salmonellosis (n = 14,264) were linked to the Netherlands Cancer Registry. Salmonella-infected patients were laboratory-confirmed under medical consultation after 1–2 weeks of illness. These datasets also contained information on Salmonella serovar and type of infection. Colon cancer risk (overall and per colon subsite) among patients with a diagnosed Salmonella infection was compared with expected colon cancer risk in the general population. Data from the nationwide registry of histo- and cytopathology (PALGA) and Statistics Netherlands (CBS) allowed assessing potential effects of age, gender, latency, socioeconomic status, genetic predisposition, inflammatory bowel disease (IBD), and tumor features. We found that compared to the general population, colon cancer risk was significantly increased (standardized incidence ratio [SIR] 1.54; 95%CI 1.09–2.10) among patients with Salmonella infection diagnosed transverse colon (SIR 2.12; 95%CI 1.38–3.09) after S. Enteritidis infection (SIR 2.97; 95%CI 1.73–4.76). Salmonellosis occurred more frequently among colon cancer patients with pre-infectious IBD, a known risk factor for colon cancer. Colon tumors of patients with a history of Salmonella infection were mostly of low grade. Conclusions Patients diagnosed with severe

Endoscopic Localization of Colon Cancer Is Frequently Inaccurate.

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Nayor, Jennifer; Rotman, Stephen R; Chan, Walter W; Goldberg, Joel E; Saltzman, John R

2017-08-01

Colonoscopic location of a tumor can influence both the surgical procedure choice and overall treatment strategy. To determine the accuracy of colonoscopy in determining the location of colon cancer compared to surgical localization and to elucidate factors that predict discordant colon cancer localization. We conducted a retrospective cross-sectional study of colon cancers diagnosed on colonoscopy at two academic tertiary-care hospitals and two affiliated community hospitals from 2012 to 2014. Colon cancer location was obtained from the endoscopic and surgical pathology reports and characterized by colon segment. We collected data on patient demographics, tumor characteristics, endoscopic procedure characteristics, surgery planned, and surgery performed. Univariate analyses using Chi-squared test and multivariate analysis using forward stepwise logistic regression were performed to determine factors that predict discordant colon cancer localization. There were 110 colon cancer cases identified during the study period. Inaccurate endoscopic colon cancer localization was found in 29% (32/110) of cases. These included 14 cases (12.7%) that were discordant by more than one colonic segment and three cases where the presurgical planned procedure was significantly changed at the time of surgery. On univariate analyses, right-sided colon lesions were associated with increased inaccuracy (43.8 vs 24.4%, p = 0.04). On multivariate analysis, right-sided colon lesions remained independently associated with inaccuracy (OR 1.74, 95% CI 1.03-2.93, p = 0.04). Colon cancer location as determined by colonoscopy is often inaccurate, which can result in intraoperative changes to surgical management, particularly in the right colon.

A Case of Sigmoid Colon Tuberculosis Mimicking Colon Cancer

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Yu, Seong-Min; Park, Jong-Hwan; Kim, Min-Dae; Lee, Hee-Ryong; Jung, Peel; Ryu, Tae-Hyun; Choi, Seung-Ho; Lee, Il-Seon

2012-01-01

Tuberculosis of the sigmoid colon is a rare disorder. An 80-year-old man visited Bongseng Memorial Hospital for medical examination. A colonoscopy was performed, and a lesion in the sigmoid colon that was suspected to be colon cancer was found. A biopsy was performed, and tuberculous enteritis with chronic granulomatous inflammation was diagnosed. Intestinal tuberculosis is most frequent in the ileocecal area, followed by the ascending colon, transverse colon, duodenum, stomach, and sigmoid c...

Colon-available raspberry polyphenols exhibit anti-cancer effects on in vitro models of colon cancer

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McDougall Gordon

2007-01-01

Full Text Available Abstract Background There is a probable association between consumption of fruit and vegetables and reduced risk of cancer, particularly cancer of the digestive tract. This anti-cancer activity has been attributed in part to anti-oxidants present in these foods. Raspberries in particular are a rich source of the anti-oxidant compounds, such as polyphenols, anthocyanins and ellagitannins. Methods A "colon-available" raspberry extract (CARE was prepared that contained phytochemicals surviving a digestion procedure that mimicked the physiochemical conditions of the upper gastrointestinal tract. The polyphenolic-rich extract was assessed for anti-cancer properties in a series of in vitro systems that model important stages of colon carcinogenesis, initiation, promotion and invasion. Results The phytochemical composition of CARE was monitored using liquid chromatography mass spectrometry. The colon-available raspberry extract was reduced in anthocyanins and ellagitannins compared to the original raspberry juice but enriched in other polyphenols and polyphenol breakdown products that were more stable to gastrointestinal digestion. Initiation – CARE caused significant protective effects against DNA damage induced by hydrogen peroxide in HT29 colon cancer cells measured using single cell microgelelectrophoresis. Promotion – CARE significantly decreased the population of HT29 cells in the G1 phase of the cell cycle, effectively reducing the number of cells entering the cell cycle. However, CARE had no effect on epithelial integrity (barrier function assessed by recording the trans-epithelial resistance (TER of CACO-2 cell monolayers. Invasion – CARE caused significant inhibition of HT115 colon cancer cell invasion using the matrigel invasion assay. Conclusion The results indicate that raspberry phytochemicals likely to reach the colon are capable of inhibiting several important stages in colon carcinogenesis in vitro.

A Colon Targeted Delivery System for Resveratrol Enriching in pH Responsive-Model

DEFF Research Database (Denmark)

Andishmand, Hashem; Hamishehkar, Hamed; Mohammadifar, Mohammad Amin

2017-01-01

Background: Resveratrol effects on the prevention and treatment of colon cancer have been well documented recently, but low solubility, rapid absorption and metabolism of resveratrol limit its beneficial effects on colon cancer. Designing a formulation that enhances the solubility of resveratrol......, protects resveratrol from oxidation and isomerization, and delivers it to the colon is a priority of food and drug industry. In this study, resveratrol-polyethylene glycol (PEG)-loaded pectin-chitosan polyelectrolyte complex was designed as a colon targeted delivery system. Methods: The effects of adding...... PEG, ultra-sonication time, pH, and pectin to chitosan ratio were investigated on particle size, polydispersity index (PDI), zeta potential by particle size analyzer, and scanning electron microscopy (SEM). Encapsulation efficiency (EE), release of resveratrol in simulated gastrointestinal fluid...

Expression and new exon mutations of the human Beta defensins and their association on colon cancer development.

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Abdelhabib Semlali

Full Text Available The development of cancer involves genetic predisposition and a variety of environmental exposures. Genome-wide linkage analyses provide evidence for the significant linkage of many diseases to susceptibility loci on chromosome 8p23, the location of the human defensin gene cluster. Human β-defensins (hBDs are important molecules of innate immunity. This study was designed to analyze the expression and genetic variations in hBDs (hBD-1, hBD-2, hBD-3 and hBD-4 and their putative association with colon cancer. hBD gene expression and relative protein expression were evaluated by Real-Time polymerase chain reaction (qPCR and immunohistochemistry, respectively, from 40 normal patients and 40 age-matched patients with colon cancer in Saudi Arabia. In addition, hBD polymorphisms were genotyped by exon sequencing and by promoter methylation. hBD-1, hBD-2, hBD-3 and hBD-4 basal messenger RNA expression was significantly lower in tumor tissues compared with normal tissues. Several insertion mutations were detected in different exons of the analyzed hBDs. However, no methylation in any hBDs promoters was detected because of the limited number of CpG islands in these regions. We demonstrated for the first time a link between hBD expression and colon cancer. This suggests that there is a significant link between innate immunity deregulation through disruption of cationic peptides (hBDs and the potential development of colon cancer.

A prognostic analysis of 895 cases of stage III colon cancer in different colon subsites.

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Zhang, Yan; Ma, Junli; Zhang, Sai; Deng, Ganlu; Wu, Xiaoling; He, Jingxuan; Pei, Haiping; Shen, Hong; Zeng, Shan

2015-09-01

Stage III colon cancer is currently treated as an entity with a unified therapeutic principle. The aim of the retrospective study is to explore the clinicopathological characteristics and outcomes of site-specific stage III colon cancers and the influences of tumor location on prognosis. Eight hundred ninety-five patients with stage III colon cancer treated with radical operation and subsequent adjuvant chemotherapy (5-fluorouracil/oxaliplatin) were divided into seven groups according to colon segment (cecum, ascending colon, hepatic flexure, transverse colon, splenic flexure, descending colon, and sigmoid colon). Expression of excision repair cross-complementing group 1 (ERCC1) and thymidylate synthase (TS) was examined by immunohistochemistry. We assessed if differences exist in patient characteristics and clinic outcomes between the seven groups. There were significant differences in tumor differentiation (P Cancer (AJCC) tumor-node-metastasis (TNM) stage (P colon. Cox regression analyses identified that tumor location was an independent prognostic factor for RFS and OS. Stage III colon cancer located proximally carried a poorer survival than that located distally. Different efficacies of FOLFOX adjuvant chemotherapy may be an important factor affecting survival of site-specific stage III colon cancers.

Generation of an inducible colon-specific Cre enzyme mouse line for colon cancer research

NARCIS (Netherlands)

Tetteh, Paul W.; Kretzschmar, Kai; Begthel, Harry; Van Den Born, Maaike; Korving, Jeroen; Morsink, Folkert; Farin, Henner; Van Es, Johan H.; Offerhaus, G. Johan A; Clevers, Hans

2016-01-01

Current mouse models for colorectal cancer often differ significantly from human colon cancer, being largely restricted to the small intestine. Here, we aim to develop a colon-specific inducible mouse model that can faithfully recapitulate human colon cancer initiation and progression. Carbonic

Radiation-associated colon cancer: A case report.

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Sasaki, Kazuhito; Ishihara, Soichiro; Hata, Keisuke; Kiyomatsu, Tomomichi; Nozawa, Hiroaki; Kawai, Kazushige; Tanaka, Toshiaki; Nishikawa, Takeshi; Otani, Kensuke; Yasuda, Koji; Kaneko, Manabu; Murono, Koji; Abe, Hiroyuki; Morikawa, Teppei; Watanabe, Toshiaki

2017-06-01

Radiation-associated colon cancer is a rare clinical entity. We herein describe the case of a patient with radiation-associated colon cancer who had undergone low anterior resection for rectal cancer following preoperative radiotherapy. Certain characteristics of radiation-associated colon cancer are highlighted. The patient was a 48-year-old man who had undergone low anterior resection for rectal cancer following preoperative radiotherapy at a total dose of 50 Gy, at the age of 29 years. When the patient presented at the University of Tokyo Hospital, 19 years after the surgery, he complained of severe anal pain and frequent defecation. Colonoscopy revealed two flat tumors in the sigmoid colon, located 10 cm to the oral side of the anastomosis site, which were diagnosed as well-differentiated adenocarcinomas. In addition, colonoscopy identified five flat polyps near the tumors, which were resected endoscopically. Computed tomography and magnetic resonance imaging revealed a mass in the sigmoid colon and no evidence of distant metastasis. Laparoscopic-assisted intersphincteric resection of the rectum and sigmoid colon with diverting ileostomy was performed. There were no specific postoperative complications and the patient was discharged from the hospital on the 20th postoperative day. On pathological examination, the resected rectum and sigmoid colon contained two separate tumors and six flat polyps. The two tumors were diagnosed as well-differentiated adenocarcinomas with invasion of the subserosa and submucosa, respectively. A total of 17 regional lymph nodes without metastasis were resected. The six flat polyps were diagnosed as tubular adenomas. We herein present a case of a radiation-associated colon cancer in a patient who had undergone low anterior resection for rectal cancer following preoperative radiotherapy 19 years prior. Colonoscopic surveillance of radiation-associated colon cancer may be indicated for rectal cancer patients treated with preoperative

Oncogenetic tree model of somatic mutations and DNA methylation in colon tumors.

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Sweeney, Carol; Boucher, Kenneth M; Samowitz, Wade S; Wolff, Roger K; Albertsen, Hans; Curtin, Karen; Caan, Bette J; Slattery, Martha L

2009-01-01

Our understanding of somatic alterations in colon cancer has evolved from a concept of a series of events taking place in a single sequence to a recognition of multiple pathways. An oncogenetic tree is a model intended to describe the pathways and sequence of somatic alterations in carcinogenesis without assuming that tumors will fall in mutually exclusive categories. We applied this model to data on colon tumor somatic alterations. An oncogenetic tree model was built using data on mutations of TP53, KRAS2, APC, and BRAF genes, methylation at CpG sites of MLH1 and TP16 genes, methylation in tumor (MINT) markers, and microsatellite instability (MSI) for 971 colon tumors from a population-based series. Oncogenetic tree analysis resulted in a reproducible tree with three branches. The model represents methylation of MINT markers as initiating a branch and predisposing to MSI, methylation of MHL1 and TP16, and BRAF mutation. APC mutation is the first alteration in an independent branch and is followed by TP53 mutation. KRAS2 mutation was placed a third independent branch, implying that it neither depends on, nor predisposes to, the other alterations. Individual tumors were observed to have alteration patterns representing every combination of one, two, or all three branches. The oncogenetic tree model assumptions are appropriate for the observed heterogeneity of colon tumors, and the model produces a useful visual schematic of the sequence of events in pathways of colon carcinogenesis.

IMMUNOHISTOCHEMICAL STUDY OF MSH2, MSH6, PMS2, MLH1 IN EVALUATION OF DIFFERENTIATION GRADE OF COLON ADENOCARCINOMA

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G. A. Raskin

2015-01-01

Full Text Available Microsatellite instability is associated with dysfunction of the MSH2, MLH1, PMS2 and MSH6 genes, which participate in the repair of unpaired nucleotides of DNA. It is known that microsatellite instability is an independent prognostic factor in determining the differentiation grade of colon cancer. The use of immunohistochemistry to study the repair system of unpaired nucleotides has its own characteristics and limitations. Materials and methods. The study included 39 patients with colon adenocarcinoma. Moderately-differentiated colon adenocarcinoma was the most common histological type (72 %. There were 8 % of well-differentiated and 12 % poorly-differentiated carcinomas. Immunohistochemical analysis of SH2, MSH6, PMS2 and MLH1 proteins was done according to the standard protocol. Results. Out of 39 cases, 6 (15 % had loss of expression of at least one of the studied proteins. Out of these 6 cases with indirect signs of MSI-H, 3 were poorlydifferentiated, 1 was mucinous and 2 were moderately differentiated adenocarcinomas. Conclusion. Thus, immunohistochemical analysis of DNA repair genes can be used to determine the histological differentiation of colon adenocarcinoma.

Microfluidic assembly of a nano-in-micro dual drug delivery platform composed of halloysite nanotubes and a pH-responsive polymer for colon cancer therapy.

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Li, Wei; Liu, Dongfei; Zhang, Hongbo; Correia, Alexandra; Mäkilä, Ermei; Salonen, Jarno; Hirvonen, Jouni; Santos, Hélder A

2017-01-15

Harsh conditions of the gastrointestinal tract hinder the oral delivery of many drugs. Developing oral drug delivery systems based on commercially available materials is becoming more challenging due to the demand for simultaneously delivering physicochemically different drugs for treating complex diseases. A novel architecture, namely nanotube-in-microsphere, was developed as a drug delivery platform by encapsulating halloysite nanotubes (HNTs) in a pH-responsive hydroxypropyl methylcellulose acetate succinate polymer using microfluidics. HNTs were selected as orally acceptable clay mineral and their lumen was enlarged by selective acid etching. Model drugs (atorvastatin and celecoxib) with different physicochemical properties and synergistic effect on colon cancer prevention and inhibition were simultaneously incorporated into the microspheres at a precise ratio, with atorvastatin and celecoxib being loaded in the HNTs and polymer matrix, respectively. The microspheres showed spherical shape, narrow particle size distribution and pH-responsive dissolution behavior. This nanotube/pH-responsive polymer composite protected the loaded drugs from premature release at pH⩽6.5, but allowed their fast release and enhanced the drug permeability, and the inhibition of colon cancer cell proliferation at pH 7.4. Overall, the nano-in-micro drug delivery composite fabricated by microfluidics is a promising and flexible platform for the delivery of multiple drugs for combination therapy. Halloysite nanotubes (HNTs) are attracting increasing attention for drug delivery applications. However, conventional HNTs-based oral drug delivery systems are lack of the capability to precisely control the drug release at a desired site in the gastrointestinal tract. In this study, a nanotube-in-microsphere drug delivery platform is developed by encapsulating HNTs in a pH-responsive polymer using microfluidics. Drugs with different physicochemical properties and synergistic effect on colon

Mutations in TGFbeta-RII and BAX mediate tumor progression in the later stages of colorectal cancer with microsatellite instability

International Nuclear Information System (INIS)

Yashiro, Masakazu; Hirakawa, Kosei; Boland, C Richard

2010-01-01

Microsatellite instability (MSI) occurs in 15% of colorectal cancers (CRC). The genetic targets for mutation in the MSI phenotype include somatic mutations in the transforming growth factor beta receptor typeII (TGFbetaRII), BAX, hMSH3 and hMSH6. It is not clear how mutations of these genes mediate tumor progression in the MSI pathway, and the temporal sequence of these mutations remains uncertain. In this study, early stage CRCs were examined for frameshift mutations in these target genes, and compared with late stage tumors and CRC cell lines. We investigated 6 CRC cell lines and 71 sporadic CRCs, including 61 early stage cancers and 10 late stage cancers. Mutations of repetitive mononucleotide tracts in the coding regions of TGFbetaRII, BAX, hMSH3, hMSH6, IGFIIR and Fas antigen were identified by direct sequencing. Thirteen (18.3%) of 71 CRC, including 9/61 (14.7%) early stage cancers and 4/10 (40%) late stage cancers, were identified as MSI and analyzed for frameshift mutations. No mutation in the target genes was observed in any of the 9 early stage MSI CRCs. In contrast, frameshift mutations of TGFbetaRII, BAX, hMSH3 and hMSH6 were present in 3/4 late stage MSI tumors. There is a statistical association (p = 0.014) between mutation in any one gene and tumor stage. TGFbetaRII, BAX, hMSH3 and hMSH6 mutations are relatively late events in the genesis of MSI CRCs. The frameshift mutations in these target genes might mediate progression from early to late stage cancer, rather than mediating the adenoma to carcinoma transition

Muscarinic receptor agonists stimulate matrix metalloproteinase 1-dependent invasion of human colon cancer cells

International Nuclear Information System (INIS)

Raufman, Jean-Pierre; Cheng, Kunrong; Saxena, Neeraj; Chahdi, Ahmed; Belo, Angelica; Khurana, Sandeep; Xie, Guofeng

2011-01-01

Highlights: ► Muscarinic receptor agonists stimulated robust human colon cancer cell invasion. ► Anti-matrix metalloproteinase1 antibody pre-treatment blocks cell invasion. ► Bile acids stimulate MMP1 expression, cell migration and MMP1-dependent invasion. -- Abstract: Mammalian matrix metalloproteinases (MMPs) which degrade extracellular matrix facilitate colon cancer cell invasion into the bloodstream and extra-colonic tissues; in particular, MMP1 expression correlates strongly with advanced colon cancer stage, hematogenous metastasis and poor prognosis. Likewise, muscarinic receptor signaling plays an important role in colon cancer; muscarinic receptors are over-expressed in colon cancer compared to normal colon epithelial cells. Muscarinic receptor activation stimulates proliferation, migration and invasion of human colon cancer cells. In mouse intestinal neoplasia models genetic ablation of muscarinic receptors attenuates carcinogenesis. In the present work, we sought to link these observations by showing that MMP1 expression and activation plays a mechanistic role in muscarinic receptor agonist-induced colon cancer cell invasion. We show that acetylcholine, which robustly increases MMP1 expression, stimulates invasion of HT29 and H508 human colon cancer cells into human umbilical vein endothelial cell monolayers – this was abolished by pre-incubation with atropine, a non-selective muscarinic receptor inhibitor, and by pre-incubation with anti-MMP1 neutralizing antibody. Similar results were obtained using a Matrigel chamber assay and deoxycholyltaurine (DCT), an amidated dihydroxy bile acid associated with colon neoplasia in animal models and humans, and previously shown to interact functionally with muscarinic receptors. DCT treatment of human colon cancer cells resulted in time-dependent, 10-fold increased MMP1 expression, and DCT-induced cell invasion was also blocked by pre-treatment with anti-MMP1 antibody. This study contributes to understanding

Muscarinic receptor agonists stimulate matrix metalloproteinase 1-dependent invasion of human colon cancer cells

Energy Technology Data Exchange (ETDEWEB)

Raufman, Jean-Pierre, E-mail: jraufman@medicine.umaryland.edu [Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD (United States); Cheng, Kunrong; Saxena, Neeraj; Chahdi, Ahmed; Belo, Angelica; Khurana, Sandeep; Xie, Guofeng [Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD (United States)

2011-11-18

Highlights: Black-Right-Pointing-Pointer Muscarinic receptor agonists stimulated robust human colon cancer cell invasion. Black-Right-Pointing-Pointer Anti-matrix metalloproteinase1 antibody pre-treatment blocks cell invasion. Black-Right-Pointing-Pointer Bile acids stimulate MMP1 expression, cell migration and MMP1-dependent invasion. -- Abstract: Mammalian matrix metalloproteinases (MMPs) which degrade extracellular matrix facilitate colon cancer cell invasion into the bloodstream and extra-colonic tissues; in particular, MMP1 expression correlates strongly with advanced colon cancer stage, hematogenous metastasis and poor prognosis. Likewise, muscarinic receptor signaling plays an important role in colon cancer; muscarinic receptors are over-expressed in colon cancer compared to normal colon epithelial cells. Muscarinic receptor activation stimulates proliferation, migration and invasion of human colon cancer cells. In mouse intestinal neoplasia models genetic ablation of muscarinic receptors attenuates carcinogenesis. In the present work, we sought to link these observations by showing that MMP1 expression and activation plays a mechanistic role in muscarinic receptor agonist-induced colon cancer cell invasion. We show that acetylcholine, which robustly increases MMP1 expression, stimulates invasion of HT29 and H508 human colon cancer cells into human umbilical vein endothelial cell monolayers - this was abolished by pre-incubation with atropine, a non-selective muscarinic receptor inhibitor, and by pre-incubation with anti-MMP1 neutralizing antibody. Similar results were obtained using a Matrigel chamber assay and deoxycholyltaurine (DCT), an amidated dihydroxy bile acid associated with colon neoplasia in animal models and humans, and previously shown to interact functionally with muscarinic receptors. DCT treatment of human colon cancer cells resulted in time-dependent, 10-fold increased MMP1 expression, and DCT-induced cell invasion was also blocked by pre

Molecular genetic approach for screening of hereditary non-polyposis colorectal cancer

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Metka Ravnik-Glavač

2005-07-01

Full Text Available Background: The main goal of knowledge concerning human diseases is to transfer as much as possible useful information into clinical applications. Hereditary non-polyposis colorectal cancer (HNPCC is the most common autosomal dominant inherited predisposition for colorectal cancer, accounting for 1–2% of all bowel cancer. The only way to diagnose HNPCC is by a family history consistent with the disease defined by International Collaborative Group on HNPCC (Amsterdam criteria I and II. The main molecular cause of HNPCC is a constitutional mutation in one of the mismatch repair (MMR genes. Since HNPCC mutations have been detected also in families that did not fulfil the Amsterdam criteria, molecular genetic characteristics of HNPCC cancers have been proposed as valuable first step in HNPCC identification. Microsatellite instability is present in about 90% of cancers of HNPCC patients. However, of all MSI colorectal cancers 80– 90% are sporadic. Several molecular mechanisms have been uncovered that enable distinguishing to some extent between sporadic and HNPCC cancers with MSI including hypermethylation of hMLH1 promoter and frequent mutations in BAX and TGFBR2 in sporadic CRC with MSI-H.Conclusions: The determination of MSI status and careful separation of MSI positive colorectal cancer into sporadic MSIL, sporadic MSI-H, and HNPCC MSI-H followed by mutation detection in MMR genes is important for prevention, screening and management of colorectal cancer. In some studies we and others have already shown that large-scale molecular genetic analysis for HNPCC can be done and is sensitive enough to approve population screening. Population screening includes also colonoscopy which is restricted only to the obligate carriers of the mutation. This enables that the disease is detected in earlier stages which would greatly decrease medical treatment costs and most importantly decrease mortality. In Slovenia we have started population screening based

Prognostic value of BRAF and KRAS mutation status in stage II and III microsatellite instable colon cancers

NARCIS (Netherlands)

de Cuba, E. M. V.; Snaebjornsson, P.; Heideman, D. A. M.; van Grieken, N. C. T.; Bosch, L. J. W.; Fijneman, R. J. A.; Belt, E.; Bril, H.; Stockmann, H. B. A. C.; Hooijberg, E.; Punt, C. J. A.; Koopman, M.; Nagtegaal, I. D.; Coupé, V. H. M.; Carvalho, B.; Meijer, G. A.

2016-01-01

Microsatellite instability (MSI) has been associated with favourable survival in early stage colorectal cancer (CRC) compared to microsatellite stable (MSS) CRC. The BRAF V600E mutation has been associated with worse survival in MSS CRC. This mutation occurs in 40% of MSI CRC and it is unclear

Colon and rectal cancer

International Nuclear Information System (INIS)

Saldombide, L.; Cordoba, A.

2010-01-01

This study is about the diagnosis, therapy and monitoring of colon cancer. The techniques used are the endoscopy with biopsy in the pre and post operative colon surgery, abdominal ultrasound, chest X-ray studies of hemogram as well as liver and renal function

Colonic epithelium is diffusely abnormal in ulcerative colitis and colorectal cancer.

OpenAIRE

Gibson, P; Rosella, O; Nov, R; Young, G

1995-01-01

The hypothesis that the colonic epithelium is diffusely abnormal in ulcerative colitis was examined by comparing disease related responses in expression of markers of differentiation by colonic crypt cells to culture with and without butyrate. Cells were isolated from patients with normal colon (15), cancer (24), ulcerative colitis (19), or Crohn's disease (16). Alkaline phosphatase activities were measured in cell homogenates and the rate of glycoprotein synthesis assessed at the end of 24 h...

Melanosis coli in patients with colon cancer

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Dorota Biernacka-Wawrzonek

2016-12-01

Full Text Available Intoduction: Melanosis coli is a benign lesion affecting the mucosa of the large intestine. There is a relationship between the presence of melanosis and anthraquinone laxative use. Melanosis coli is also observed in patients with colon cancer, but there is doubt whether these two conditions are related. Aim : To analyze the correlation between melanosis and colon cancer. Material and methods: We analyzed retrospectively 436 patients undergoing colon cancer surgery. There were 246 women and 190 men. Patients were divided into three age groups: under 50 years, between 51 and 65 years, and over 66 years. We analyzed sections of the cancer and intestinal mucosa from the tumor’s proximal (2–5 cm and distal (8–10 cm zone. Results : Melanosis coli was present in 52 patients, which represents 11.9% of patients with colon cancer. More often it was present in women. The most common location of melanosis and colon cancer was the terminal part of the large intestine. In patients below 50 years of age in both sexes melanosis coli did not occur. In men, melanosis was more common in the age group over 66 years. Intensity of pigmentation was higher in the tumor’s distal zone. Conclusions : The incidence of melanosis coli increases with age, similar to that of colon cancer. Melanosis was not present inside tumors, in almost half of the cases it was not present in the proximal zone, and the degree of pigmentation increased in distal zone. The cause-effect relationship between melanosis coli and colon cancer remains uncertain.

Dietary Patterns and Colon Cancer Risk in Whites and African Americans in the North Carolina Colon Cancer Study

OpenAIRE

Satia, Jessie A.; Tseng, Marilyn; Galanko, Joseph A.; Martin, Christopher; Sandler, Robert S.

2009-01-01

We examined associations of dietary patterns with colon cancer risk in African Americans and Whites from a case-control study in North Carolina. Incident colon cancer cases, 40 to 80 yr (n = 636), and matched controls (n = 1,042) were interviewed in person to elicit information on potential colon cancer risk factors. A validated food frequency questionnaire adapted to include regional foods captured diet over the year prior to diagnosis (cases) or interview date (controls). Three meaningful i...

Prognostic impact of Metadherin-SND1 interaction in colon cancer.

Science.gov (United States)

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

2012-12-01

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

Colorectal Cancer "Methylator Phenotype": Fact or Artifact?

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Charles Anacleto

2005-04-01

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

Colon cancer information as a source of exercise motivation for relatives of patients with colon cancer.

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McGowan, Erin L; Prapavessis, Harry

2010-12-01

Using a Protection Motivation Theory (PMT) framework, this study examined whether factual colon cancer information is a meaningful source of exercise motivation for relatives of patients with colon cancer. One hundred sixty-six inactive relatives were randomly assigned to one of two treatment conditions: PMT group (intervention); and non-PMT group (attention control). At baseline (T1) participants completed demographic information, a questionnaire designed to assess their beliefs toward exercise and colon cancer as well as their exercise intentions. At T2 (one week following T1) participants watched one of two DVD videos that were created for the study. The intervention DVD contained exercise and colon cancer information that was yoked within the four major components of PMT: perceived vulnerability (PV); perceived severity (PS); response efficacy (RE); and self-efficacy (SE), while the attention control DVD contained general diet and cancer information. Immediately following watching the DVD, participants completed the same measures as in T1. Participants assigned to the PMT intervention group showed significant improvement in PV, RE, SE and exercise intentions, whereas participants assigned to the attention control group showed significant improvement only in RE. RE, SE, and PS made significant and unique contributions to prediction of exercise intention. Overall, the results of the present study demonstrate that a single exposure media intervention grounded in a PMT framework can change individuals' exercise and colon cancer beliefs, as well as change their exercise intentions. Implications of these findings and direction for future research are discussed.

Diet, genes, and microbes: complexities of colon cancer prevention.

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Birt, Diane F; Phillips, Gregory J

2014-01-01

Colorectal cancer is one of the leading causes of cancer-related deaths in the United States, and generally, as countries climb the economic ladder, their rates of colon cancer increase. Colon cancer was an early disease where key genetic mutations were identified as important in disease progression, and there is considerable interest in determining whether specific mutations sensitize the colon to cancer prevention strategies. Epidemiological studies have revealed that fiber- and vegetable-rich diets and physical activity are associated with reduced rates of colon cancer, while consumption of red and processed meat, or alcoholic beverages, and overconsumption as reflected in obesity are associated with increased rates. Animal studies have probed these effects and suggested directions for further refinement of diet in colon cancer prevention. Recently a central role for the microorganisms in the gastrointestinal tract in colon cancer development is being probed, and it is hypothesized that the microbes may integrate diet and host genetics in the etiology of the disease. This review provides background on dietary, genetic, and microbial impacts on colon cancer and describes an ongoing project using rodent models to assess the ability of digestion-resistant starch in the integration of these factors with the goal of furthering colon cancer prevention.

Molecular profile and copy number analysis of sporadic colorectal cancer in Taiwan

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Li Ling-Hui

2011-06-01

Full Text Available Abstract Background Colorectal cancer (CRC is a major health concern worldwide, and recently becomes the most common cancer in Asia. The case collection of this study is one of the largest sets of CRC in Asia, and serves as representative data for investigating genomic differences between ethnic populations. We took comprehensive and high-resolution approaches to compare the clinicopathologic and genomic profiles of microsatellite instability (MSI vs. microsatellite stability (MSS in Taiwanese sporadic CRCs. Methods 1,173 CRC tumors were collected from the Taiwan population, and sequencing-based microsatellite typing assay was used to determine MSI and MSS. Genome-wide SNP array was used to detect CN alterations in 16 MSI-H and 13 MSS CRCs and CN variations in 424 general controls. Gene expression array was used to evaluate the effects of CN alterations, and quantitative PCR methods were used to replicate the findings in independent clinical samples. Results These 1,173 CRC tumors can be classified into 75 high-frequency MSI (MSI-H (6.4%, 96 low-frequency MSI (8.2% and 1,002 MSS (85.4%. Of the 75 MSI-H tumors, 22 had a BRAF mutation and 51 showed MLH1 promoter hypermethylation. There were distinctive differences in the extent of CN alterations between CRC MSS and MSI-H subtypes (300 Mb vs. 42 Mb per genome, p-value Conclusions Sporadic CRCs with MSI-H displayed distinguishable clinicopathologic features, which differ from those of MSS. Genomic profiling of the two types of sporadic CRCs revealed significant differences in the extent and distribution of CN alterations in the cancer genome. More than half of expressed genes showing CN differences can directly contribute to their expressional diversities, and the biological functions of the genes associated with CN changes in sporadic CRCs warrant further investigation to establish their possible clinical implications.

Emergency management of acute colonic cancer obstruction.

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Gainant, A

2012-02-01

Emergency management of obstructing colonic cancer depends on both tumor location and stage, general condition of the patient and surgeon's experience. Right sided or transverse colon obstructing cancers are usually treated by right hemicolectomy-extended if necessary to the transverse colon-with primary anastomosis. For left-sided obstructing cancer, in patients with low surgical risk, primary resection and anastomosis associated with on-table irrigation or manual decompression can be performed. It prevents the confection of a loop colostomy but presents the risk of anastomotic leakage. Subtotal or total colectomy allows the surgeon to encompass distended and fecal-loaded colon, and to perform one-stage resection and anastomosis. Its disadvantage is an increased daily frequency of stools. It must be performed only in cases of diastatic colon perforation or synchronous right colonic cancer. In patients with high surgical risk, Hartmann procedure must be preferred. It allows the treatment of both obstruction and cancer, and prevents anastomotic leakage but needs a second operation to reverse the colostomy. Colonic stenting is clinically successful in up to 90% in specialized groups. It is used as palliation in patients with disseminated disease or bridge to surgery in the others. If stent insertion is not possible, loop colostomy is still indicated in patients at high surgical risk. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Improved survival for rectal cancer compared to colon cancer: the four cohort study.

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Buchwald, Pamela; Hall, Claire; Davidson, Callum; Dixon, Liane; Dobbs, Bruce; Robinson, Bridget; Frizelle, Frank

2018-03-01

Colorectal cancer (CRC) is the third most common cancer worldwide. This study was undertaken to evaluate survival outcomes and changes of disease outcomes of CRC patients over the last decades. A retrospective analysis of CRC patients in Christchurch was performed in four patient cohorts at 5 yearly intervals; 1993-94, 1998-99, 2004-05 and 2009. Data on cancer location, stage, surgical and oncological treatment and survival were collected. Univariate, multivariate and Kaplan-Meier survival analysis were performed. There were 1391 patients (355, 317, 419 and 300 per cohort), 1037 colon and 354 rectal cancers, respectively. For colon cancer, right-sided cancers appeared more common in later cohorts (P = 0.01). There was a significant decrease in the number of permanent stomas for colon cancer patients (P = 0.001). There was an analogous trend for rectal cancers (P = 0.075). More CRC patients with stage IV disease were treated surgically (P = 0.001) and colon cancer stages I and II tended to have increased survival if operated by a colorectal surgeon (P = 0.06). Oncology referrals have increased remarkably (P = 0.001). Overall 56% of patients were alive at 5 years however rectal cancer patients had significantly better 5-year survival than those with colon cancer (P rectal cancer patients have a better 5-year survival than colon cancer patients. The improved survival with early stage colon cancers operated on by specialist colorectal surgeons needs further exploration. © 2016 Royal Australasian College of Surgeons.

IFNγ Induces DNA Methylation-Silenced GPR109A Expression via pSTAT1/p300 and H3K18 Acetylation in Colon Cancer.

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Bardhan, Kankana; Paschall, Amy V; Yang, Dafeng; Chen, May R; Simon, Priscilla S; Bhutia, Yangzom D; Martin, Pamela M; Thangaraju, Muthusamy; Browning, Darren D; Ganapathy, Vadivel; Heaton, Christopher M; Gu, Keni; Lee, Jeffrey R; Liu, Kebin

2015-07-01

Short-chain fatty acids, metabolites produced by colonic microbiota from fermentation of dietary fiber, act as anti-inflammatory agents in the intestinal tract to suppress proinflammatory diseases. GPR109A is the receptor for short-chain fatty acids. The functions of GPR109A have been the subject of extensive studies; however, the molecular mechanisms underlying GPR109A expression is largely unknown. We show that GPR109A is highly expressed in normal human colon tissues, but is silenced in human colon carcinoma cells. The GPR109A promoter DNA is methylated in human colon carcinoma. Strikingly, we observed that IFNγ, a cytokine secreted by activated T cells, activates GPR109A transcription without altering its promoter DNA methylation. Colon carcinoma grows significantly faster in IFNγ-deficient mice than in wild-type mice in an orthotopic colon cancer mouse model. A positive correlation was observed between GPR109A protein level and tumor-infiltrating T cells in human colon carcinoma specimens, and IFNγ expression level is higher in human colon carcinoma tissues than in normal colon tissues. We further demonstrated that IFNγ rapidly activates pSTAT1 that binds to the promoter of p300 to activate its transcription. p300 then binds to the GPR109A promoter to induce H3K18 hyperacetylation, resulting in chromatin remodeling in the methylated GPR109A promoter. The IFNγ-activated pSTAT1 then directly binds to the methylated but hyperacetylated GPR109 promoter to activate its transcription. Overall, our data indicate that GPR109A acts as a tumor suppressor in colon cancer, and the host immune system might use IFNγ to counteract DNA methylation-mediated GPR109A silencing as a mechanism to suppress tumor development. ©2015 American Association for Cancer Research.

Microsatellite instability in colorectal cancer and association with thymidylate synthase and dihydropyrimidine dehydrogenase expression

International Nuclear Information System (INIS)

Jensen, Søren A; Vainer, Ben; Kruhøffer, Mogens; Sørensen, Jens B

2009-01-01

Microsatellite instability (MSI) refers to mutations in short motifs of tandemly repeated nucleotides resulting from replication errors and deficient mismatch repair (MMR). Colorectal cancer with MSI has characteristic biology and chemosensitivity, however the molecular basis remains unclarified. The association of MSI and MMR status with outcome and with thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) expression in colorectal cancer were evaluated. MSI in five reference loci, MMR enzymes (hMSH2, hMSH6, hMLH1 and hPMS2), thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) expression were assessed in paraffin embedded tumor specimens, and associated with outcome in 340 consecutive patients completely resected for colorectal cancer stages II-IV and subsequently receiving adjuvant 5-fluorouracil therapy. MSI was found in 43 (13.8%) tumors. Absence of repair protein expression was assessed in 52 (17.0%) tumors, which had primarily lost hMLH1 in 39 (12.7%), hMSH2 in 5 (1.6%), and hMSH6 in 8 (2.6%) tumors. In multivariate analysis MSI (instable) compared to MSS (stable) tumors were significantly associated with lower risk of recurrence (hazard ratio (HR) = 0.3; 95% CI: 0.2–0.7; P = 0.0007) and death (HR = 0.4; 95% CI: 0.2–0.9; P = 0.02) independently of the TS and DPD expressions. A direct relationship between MSI and TS intensity (P = 0.001) was found, while there was no significant association with DPD intensity (P = 0.1). The favourable outcome of MSI colorectal carcinomas is ascribed mainly to the tumor biology and to a lesser extent to antitumor response to 5-fluorouracil therapy. There is no evidence that differential TS or DPD expression may account for these outcome characteristics

Intestinal helminth infection drives carcinogenesis in colitis-associated colon cancer.

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Eva Pastille

2017-09-01

Full Text Available Inflammatory bowel diseases (IBD are chronic inflammatory disorders of the gastrointestinal tract, strongly associated with an increased risk of colorectal cancer development. Parasitic infections caused by helminths have been shown to modulate the host's immune response by releasing immunomodulatory molecules and inducing regulatory T cells (Tregs. This immunosuppressive state provoked in the host has been considered as a novel and promising approach to treat IBD patients and alleviate acute intestinal inflammation. On the contrary, specific parasite infections are well known to be directly linked to carcinogenesis. Whether a helminth infection interferes with the development of colitis-associated colon cancer (CAC is not yet known. In the present study, we demonstrate that the treatment of mice with the intestinal helminth Heligmosomoides polygyrus at the onset of tumor progression in a mouse model of CAC does not alter tumor growth and distribution. In contrast, H. polygyrus infection in the early inflammatory phase of CAC strengthens the inflammatory response and significantly boosts tumor development. Here, H. polygyrus infection was accompanied by long-lasting alterations in the colonic immune cell compartment, with reduced frequencies of colonic CD8+ effector T cells. Moreover, H. polygyrus infection in the course of dextran sulfate sodium (DSS mediated colitis significantly exacerbates intestinal inflammation by amplifying the release of colonic IL-6 and CXCL1. Thus, our findings indicate that the therapeutic application of helminths during CAC might have tumor-promoting effects and therefore should be well-considered.

Enterobacter Strains Might Promote Colon Cancer.

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Yurdakul, Dilşad; Yazgan-Karataş, Ayten; Şahin, Fikrettin

2015-09-01

Many studies have been performed to determine the interaction between bacterial species and cancer. However, there has been no attempts to demonstrate a possible relationship between Enterobacter spp. and colon cancer so far. Therefore, in the present study, it is aimed to investigate the effects of Enterobacter strains on colon cancer. Bacterial proteins were isolated from 11 Enterobacter spp., one Morganella morganii, and one Escherichia coli strains, and applied onto NCM460 (Incell) and CRL1790 (ATCC) cell lines. Cell viability and proliferation were determined in MTS assay. Flow Cytometry was used to detect CD24 level and apoptosis. Real-Time PCR studies were performed to determine NFKB and Bcl2 expression. Graphpad Software was used for statistical analysis. The results showed that proteins, isolated from the Enterobacter spp., have significantly increased cell viability and proliferation, while decreasing the apoptosis of the cell lines tested. The data in the present study indicated that Enterobacter strains might promote colon cancer. Moreover, Enterobacter spp. could be a clinically important factor for colon cancer initiation and progression. Studies can be extended on animal models in order to develop new strategies for treatment.

Combinatorial nanomedicines for colon cancer therapy.

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Anitha, A; Maya, S; Sivaram, Amal J; Mony, U; Jayakumar, R

2016-01-01

Colon cancer is one of the major causes of cancer deaths worldwide. Even after surgical resection and aggressive chemotherapy, 50% of colorectal carcinoma patients develop recurrent disease. Thus, the rationale of developing new therapeutic approaches to improve the current chemotherapeutic regimen would be highly recommended. There are reports on the effectiveness of combination chemotherapy in colon cancer and it has been practiced in clinics for long time. These approaches are associated with toxic side effects. Later, the drug delivery research had shown the potential of nanoencapsulation techniques and active targeting as an effective method to improve the effectiveness of chemotherapy with less toxicity. This current focus article provides a brief analysis of the ongoing research in the colon cancer area using the combinatorial nanomedicines and its outcome. © 2015 Wiley Periodicals, Inc.

Directory of Colon and Rectal Cancer Specialist Teams

OpenAIRE

Department of Health; Social Services and Public Safety

2004-01-01

The Directory of Colon and Rectal Cancer Specialist Teams has been produced under the auspices of the Northern Ireland Regional Advisory Committee on Cancer. It contains details of the full membership of the clinical teams providing care for colon and rectal cancer in each of Health and Social Services Board Area. Lead Clinicians For Colon and Rectal Cancer Services (PDF 74 KB) EHSSB (PDF 198 KB) NHSSB (PDF 107 KB) SHSSB (PDF 130 KB) WHSSB (PDF 131 KB)

Differences between right- and left-sided colon cancer in patient characteristics, cancer morphology and histology.

Science.gov (United States)

Nawa, Toru; Kato, Jun; Kawamoto, Hirofumi; Okada, Hiroyuki; Yamamoto, Hiroshi; Kohno, Hiroyuki; Endo, Hisayuki; Shiratori, Yasushi

2008-03-01

Recently, the clinical and biological differences between right- and left-sided colon cancers have been widely debated. However, close analyses of these clinical differences, based on large-scale studies, have been scarcely reported. A total of 3552 consecutive Japanese colorectal cancer cases were examined and the clinical differences between right- and left-sided colon cancer cases were investigated. The proportion of right-sided colon cancer was relatively high in patients aged less than 40 years (33%) and more than 80 years (43%). The proportion of right-sided colon cancer in patients aged 40-59 years was relatively low (male 22% and female 29%). In male patients the proportion increased in the 70-79 years age group (30%), while in female patients the proportion increased in the 60-69 years age group (39%). Right-sided colon cancer was more likely to be detected at an advanced stage (T1 stage; left 22%, right 15%) (P cancer was dominant in the left colon (left 59%; right 40%) (P cancer in the right colon was significantly higher than that in the left colon (left 25%; right 44%) (P colon cancer was observed and the difference between male and female patients was highlighted. Other clinical features also differed between right- and left-sided colon cancer, suggesting that different mechanisms may be at work during right and left colon carcinogenesis.

Three-dimensional display of magnetic source imaging (MSI)

International Nuclear Information System (INIS)

Morioka, Takato; Yamamoto, Tomoya; Nishio, Shunji; Hasuo, Kanehiro; Fujii, Kiyotaka; Fukui, Masashi; Nitta, Koichi.

1995-01-01

Magnetic source imaging (MSI) is a relatively new, noninvasive technique for defining the relationship between brain structure and function of individual patients, and to establish comparisons from one patient to another. This is achieved by combining detailed neurophysiological data derived via magnetoencephalography (MEG) with neuroimaging data such as computed tomographic scan and magnetic resonance imaging (MRI). The noninvasive presurgical mapping of cortical functional somatosensory activity and the direct mapping of epilepsy-associated activity are among the neurosurgical uses that are emerging for MSI. Although the procedure provides clinically useful data, there are still limitations to two-dimensional MSI. We employ three-dimensional (3-D) MSI, superimposing MSI localizations on 3-D volumetric reconstruction of MRI. 3-D MSI enhances the visualization of the entire sensory homunculus and clearly demonstrates the spatial relationship with structural lesions. The functional localization of the epileptic focus in spatial relation to the lesion provides important clues for preoperative planning and on the epileptogenicity of the lesion. 3-D MSI improves localization of the sensory cortex and generator areas of epileptic activity. (author)

Diet, faecal pH and colorectal cancer

NARCIS (Netherlands)

Dokkum, W. van; Boer, B.C.J. de; Faassen, A. van; Pikaar, N.A.; Hermus, R.J.J.

1983-01-01

We suggest that a lower faecal pH may be correlated with a lower mortality of large-bowel cancer and that faecal pH should always be considered in epidemiological studies on the role of diet in colon carcinogenesis.

Increased colon cancer risk after severe Salmonella infection

OpenAIRE

Mughini-Gras, Lapo; Schaapveld, Michael; Kramers, Jolanda; Mooij, Sofie; Neefjes-Borst, E. Andra; van Pelt, Wilfrid; Neefjes, Jacques

2018-01-01

Background Colon cancer constitutes one of the most frequent malignancies. Previous studies showed that Salmonella manipulates host cell signaling pathways and that Salmonella Typhimurium infection facilitates colon cancer development in genetically predisposed mice. This epidemiological study examined whether severe Salmonella infection, usually acquired from contaminated food, is associated with increased colon cancer risk in humans. Methods and findings We performed a nationwide registry-b...

Butyrate Inhibits Cancerous HCT116 Colon Cell Proliferation but to a Lesser Extent in Noncancerous NCM460 Colon Cells.

Science.gov (United States)

Zeng, Huawei; Taussig, David P; Cheng, Wen-Hsing; Johnson, LuAnn K; Hakkak, Reza

2017-01-01

Butyrate, an intestinal microbiota metabolite of dietary fiber, exhibits chemoprevention effects on colon cancer development. However, the mechanistic action of butyrate remains to be determined. We hypothesize that butyrate inhibits cancerous cell proliferation but to a lesser extent in noncancerous cells through regulating apoptosis and cellular-signaling pathways. We tested this hypothesis by exposing cancerous HCT116 or non-cancerous NCM460 colon cells to physiologically relevant doses of butyrate. Cellular responses to butyrate were characterized by Western analysis, fluorescent microscopy, acetylation, and DNA fragmentation analyses. Butyrate inhibited cell proliferation, and led to an induction of apoptosis, genomic DNA fragmentation in HCT116 cells, but to a lesser extent in NCM460 cells. Although butyrate increased H3 histone deacetylation and p21 tumor suppressor expression in both cell types, p21 protein level was greater with intense expression around the nuclei in HCT116 cells when compared with that in NCM460 cells. Furthermore, butyrate treatment increased the phosphorylation of extracellular-regulated kinase 1/2 (p-ERK1/2), a survival signal, in NCM460 cells while it decreased p-ERK1/2 in HCT116 cells. Taken together, the activation of survival signaling in NCM460 cells and apoptotic potential in HCT116 cells may confer the increased sensitivity of cancerous colon cells to butyrate in comparison with noncancerous colon cells.

Generation of an inducible colon-specific Cre enzyme mouse line for colon cancer research.

Science.gov (United States)

Tetteh, Paul W; Kretzschmar, Kai; Begthel, Harry; van den Born, Maaike; Korving, Jeroen; Morsink, Folkert; Farin, Henner; van Es, Johan H; Offerhaus, G Johan A; Clevers, Hans

2016-10-18

Current mouse models for colorectal cancer often differ significantly from human colon cancer, being largely restricted to the small intestine. Here, we aim to develop a colon-specific inducible mouse model that can faithfully recapitulate human colon cancer initiation and progression. Carbonic anhydrase I (Car1) is a gene expressed uniquely in colonic epithelial cells. We generated a colon-specific inducible Car1 CreER knock-in (KI) mouse with broad Cre activity in epithelial cells of the proximal colon and cecum. Deletion of the tumor suppressor gene Apc using the Car1 CreER KI caused tumor formation in the cecum but did not yield adenomas in the proximal colon. Mutation of both Apc and Kras yielded microadenomas in both the cecum and the proximal colon, which progressed to macroadenomas with significant morbidity. Aggressive carcinomas with some invasion into lymph nodes developed upon combined induction of oncogenic mutations of Apc, Kras, p53, and Smad4 Importantly, no adenomas were observed in the small intestine. Additionally, we observed tumors from differentiated Car1-expressing cells with Apc/Kras mutations, suggesting that a top-down model of intestinal tumorigenesis can occur with multiple mutations. Our results establish the Car1 CreER KI as a valuable mouse model to study colon-specific tumorigenesis and metastasis as well as cancer-cell-of-origin questions.

Accuracy of colonoscopy in localizing colonic cancer.

Science.gov (United States)

Stanciu, C; Trifan, Anca; Khder, Saad Alla

2007-01-01

It is important to establish the precise localization of colonic cancer preoperatively; while colonoscopy is regarded as the diagnostic gold standard for colorectal cancer, its ability to localize the tumor is less reliable. To define the accuracy of colonoscopy in identifying the location of colonic cancer. All of the patients who had a colorectal cancer diagnosed by colonoscopy at the Institute of Gastroenterology and Hepatology, Iaşi and subsequently received a surgical intervention at three teaching hospitals in Iaşi, between January 2001 and December 2005, were included in this study. Endoscopic records and operative notes were carefully reviewed, and tumor localization was recorded. There were 161 patients (89 men, 72 women, aged 61.3 +/- 12.8 years) who underwent conventional surgery for colon cancer detected by colonoscopy during the study period. Twenty-two patients (13.66%) had erroneous colonoscopic localization of the tumors. The overall accuracy of preoperative colonoscopic localization was 87.58%. Colonoscopy is an accurate, reliable method for locating colon cancer, although additional techniques (i.e., endoscopic tattooing) should be performed at least for small lesions.

Neoadjuvant chemotherapy in locally advanced colon cancer

DEFF Research Database (Denmark)

Jakobsen, Anders; Andersen, Fahimeh; Fischer, Anders

2015-01-01

BACKGROUND: Neoadjuvant chemotherapy has proven valuable in several tumors, but it has not been elucidated in colon cancer. The present phase II trial addressed the issue in high-risk patients selected by computed tomography (CT) scan. MATERIAL AND METHODS: Patients with resectable colon cancer...... 32% (p = 0.005) translating into a three-year DFS of 94% versus 63% (p = 0.005). CONCLUSION: Neoadjuvant chemotherapy in colon cancer is feasible and the results suggest that a major part of the patients can be spared adjuvant chemotherapy. Validation in a randomized trial is warranted....

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

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... The CDC Cancel Submit Search The CDC Colorectal (Colon) Cancer Note: Javascript is disabled or is not supported ... Risk Assessment Tool (National Cancer Institute) Learning About Colon Cancer Stay Informed Language: English Español (Spanish) File Formats ...

CT staging of colon cancer

International Nuclear Information System (INIS)

Dighe, S.; Swift, I.; Brown, G.

2008-01-01

Computer tomography (CT) has been the principal investigation in the staging of colon cancers. The information obtained with routine CT has been limited to identifying the site of the tumour, size of the tumour, infiltration into surrounding structures and metastatic spread. The Foxtrot trial National Cancer Research Institute (NCRI) has been specifically designed to evaluate the efficacy of neoadjuvant treatment in colon cancers by using preoperative chemotherapy with or without an anti-Epidermal Growth Factor Receptor (EGFR) monoclonal antibody to improve outcome in high-risk operable colon cancer. Patients are selected based on their staging CT examination. The criteria for poor prognosis are T4 and T3 tumours with more than 5 mm extramural depth. Thus the success of the trial would depend upon the confidence of the radiologist to identify the patients that would receive the neoadjuvant treatment. The aim of this review is to explain the process of identifying high-risk features seen on the staging CT images. This will help to identify a cohort of patients that could truly benefit from neoadjuvant strategies

CT staging of colon cancer

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Dighe, S. [Department of Radiology, Royal Marsden Hospital, Sutton SM5 2TT (United Kingdom); Swift, I. [Department of Surgery, Mayday University Hospital, Croydon CR7 7YE (United Kingdom); Brown, G. [Department of Radiology, Royal Marsden Hospital, Sutton SM5 2TT (United Kingdom)], E-mail: gina.brown@rmh.nhs.uk

2008-12-15

Computer tomography (CT) has been the principal investigation in the staging of colon cancers. The information obtained with routine CT has been limited to identifying the site of the tumour, size of the tumour, infiltration into surrounding structures and metastatic spread. The Foxtrot trial National Cancer Research Institute (NCRI) has been specifically designed to evaluate the efficacy of neoadjuvant treatment in colon cancers by using preoperative chemotherapy with or without an anti-Epidermal Growth Factor Receptor (EGFR) monoclonal antibody to improve outcome in high-risk operable colon cancer. Patients are selected based on their staging CT examination. The criteria for poor prognosis are T4 and T3 tumours with more than 5 mm extramural depth. Thus the success of the trial would depend upon the confidence of the radiologist to identify the patients that would receive the neoadjuvant treatment. The aim of this review is to explain the process of identifying high-risk features seen on the staging CT images. This will help to identify a cohort of patients that could truly benefit from neoadjuvant strategies.

Comprehensive analysis of CpG island methylator phenotype (CIMP)-high, -low, and -negative colorectal cancers based on protein marker expression and molecular features.

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Zlobec, Inti; Bihl, Michel; Foerster, Anja; Rufle, Alex; Lugli, Alessandro

2011-11-01

CpG island methylator phenotype (CIMP) is being investigated for its role in the molecular and prognostic classification of colorectal cancer patients but is also emerging as a factor with the potential to influence clinical decision-making. We report a comprehensive analysis of clinico-pathological and molecular features (KRAS, BRAF and microsatellite instability, MSI) as well as of selected tumour- and host-related protein markers characterizing CIMP-high (CIMP-H), -low, and -negative colorectal cancers. Immunohistochemical analysis for 48 protein markers and molecular analysis of CIMP (CIMP-H: ≥ 4/5 methylated genes), MSI (MSI-H: ≥ 2 instable genes), KRAS, and BRAF were performed on 337 colorectal cancers. Simple and multiple regression analysis and receiver operating characteristic (ROC) curve analysis were performed. CIMP-H was found in 24 cases (7.1%) and linked (p CIMP-low or -negative cases. Of the 48 protein markers, decreased levels of RKIP (p = 0.0056), EphB2 (p = 0.0045), CK20 (p = 0.002), and Cdx2 (p CIMP-H, independently of MSI status. In addition to the expected clinico-pathological and molecular associations, CIMP-H colorectal cancers are characterized by a loss of protein markers associated with differentiation, and metastasis suppression, and have increased CD8+ T-lymphocytes regardless of MSI status. In particular, Cdx2 loss seems to strongly predict CIMP-H in both microsatellite-stable (MSS) and MSI-H colorectal cancers. Cdx2 is proposed as a surrogate marker for CIMP-H. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

BRCA2, EGFR, and NTRK mutations in mismatch repair-deficient colorectal cancers with MSH2 or MLH1 mutations.

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Deihimi, Safoora; Lev, Avital; Slifker, Michael; Shagisultanova, Elena; Xu, Qifang; Jung, Kyungsuk; Vijayvergia, Namrata; Ross, Eric A; Xiu, Joanne; Swensen, Jeffrey; Gatalica, Zoran; Andrake, Mark; Dunbrack, Roland L; El-Deiry, Wafik S

2017-06-20

Deficient mismatch repair (MMR) and microsatellite instability (MSI) contribute to ~15% of colorectal cancer (CRCs). We hypothesized MSI leads to mutations in DNA repair proteins including BRCA2 and cancer drivers including EGFR. We analyzed mutations among a discovery cohort of 26 MSI-High (MSI-H) and 558 non-MSI-H CRCs profiled at Caris Life Sciences. Caris-profiled MSI-H CRCs had high mutation rates (50% vs 14% in non-MSI-H, P MLH1-mutant CRCs showed higher mutation rates in BRCA2 compared to non-MSH2/MLH1-mutant tumors (38% vs 6%, P MLH1-mutant CRCs included 75 unique mutations not known to occur in breast or pancreatic cancer per COSMIC v73. Only 5 deleterious BRCA2 mutations in CRC were previously reported in the BIC database as germ-line mutations in breast cancer. Some BRCA2 mutations were predicted to disrupt interactions with partner proteins DSS1 and RAD51. Some CRCs harbored multiple BRCA2 mutations. EGFR was mutated in 45.5% of MSH2/MLH1-mutant and 6.5% of non-MSH2/MLH1-mutant tumors (P MLH1-mutant CRC including NTRK1 I699V, NTRK2 P716S, and NTRK3 R745L. Our findings have clinical relevance regarding therapeutic targeting of BRCA2 vulnerabilities, EGFR mutations or other identified oncogenic drivers such as NTRK in MSH2/MLH1-mutant CRCs or other tumors with mismatch repair deficiency.

[Expression and significance of CK7 and CK19 in colon cancer].

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Zhang, Xin; Zheng, Peng-sheng

2010-02-01

To detect the cytokeratin (CK) genes expression in the colon cancer, and investigate the expression variability in different pathological types and clinical stages. The CK gene expression pattern in normal colon, colon cancer tissues and colon cancer cell lines were analyzed by using Immunohistochemical, Immunocytochemical and Western blot ways. CK7 and CK19 didn't express in normal colon tissues. CK7 was low or not expressed in the colon cancer, and CK19 was highly expressed in the colon cancer. There were significant deviation (Pcolon cancer, and CK7-)/CK19+ may be one of the expression characteristics in colon cancer.

Exosomes from human colorectal cancer induce a tumor-like behavior in colonic mesenchymal stromal cells.

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Lugini, Luana; Valtieri, Mauro; Federici, Cristina; Cecchetti, Serena; Meschini, Stefania; Condello, Maria; Signore, Michele; Fais, Stefano

2016-08-02

Cancer cells, including colorectal cancer ones (CRC), release high amounts of nanovesicles (exosomes), delivering biochemical messages for paracrine or systemic crosstalk. Mesenchymal stromal cells (MSCs) have been shown to play contradicting roles in tumor progression. CRC exosomes induce in cMSCs: i) atypical morphology, higher proliferation, migration and invasion; ii) formation of spheroids; iii) an acidic extracellular environment associated with iv) a plasma membrane redistribution of vacuolar H+-ATPase and increased expression of CEA. Colon cancer derived MSCs, which were isolated from tumor masses, produce umbilicated spheroids, a future frequently observed in the inner core of rapidly growing tumors and recapitulate the changes observed in normal colonic MSCs exposed to CRC exosomes. Tissue specific colonic (c)MSCs were exposed to primary or metastatic CRC exosomes and analysed by light and electron microscopy, proliferation in 2D and 3D cultures, migration and invasion assays, Western blot and confocal microscopy for vacuolar H+-ATPase expression. CRC exosomes are able to induce morphological and functional changes in colonic MSCs, which may favour tumor growth and its malignant progression. Our results suggest that exosomes are actively involved in cancer progression and that inhibiting tumor exosome release may represent a way to interfere with cancer.

Urotensin-II receptor is over-expressed in colon cancer cell lines and in colon carcinoma in humans.

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Federico, Alessandro; Zappavigna, Silvia; Romano, Marco; Grieco, Paolo; Luce, Amalia; Marra, Monica; Gravina, Antonietta Gerarda; Stiuso, Paola; D'Armiento, Francesco Paolo; Vitale, Giovanni; Tuccillo, Concetta; Novellino, Ettore; Loguercio, Carmela; Caraglia, Michele

2014-01-01

Urotensin (U)-II receptor (UTR) has been previously reported to be over-expressed in a number of tumours. Whether UTR-related pathway plays a role in colon carcinogenesis is unknown. We evaluated UTR protein and mRNA expression in human epithelial colon cancer cell lines and in normal colon tissue, adenomatous polyps and colon cancer. U-II protein expression was assessed in cancer cell lines. Moreover, we evaluated the effects of U-II(4-11) (an UTR agonist), antagonists and knockdown of UTR protein expression through a specific shRNA, on proliferation, invasion and motility of human colon cancer cells. Cancer cell lines expressed U-II protein and UTR protein and mRNA. By immunohistochemistry, UTR was expressed in 5-30% of epithelial cells in 45 normal controls, in 30-48% in 21 adenomatous polyps and in 65-90% in 48 colon adenocarcinomas. UTR mRNA expression was increased by threefold in adenomatous polyps and eightfold in colon cancer, compared with normal colon. U-II(4-11) induced a 20-40% increase in cell growth while the blockade of the receptor with specific antagonists caused growth inhibition of 20-40%. Moreover, the knock down of UTR with a shRNA or the inhibition of UTR with the antagonist urantide induced an approximately 50% inhibition of both motility and invasion. UTR appears to be involved in the regulation of colon cancer cell invasion and motility. These data suggest that UTR-related pathway may play a role in colon carcinogenesis and that UTR may function as a target for therapeutic intervention in colon cancer. © 2013 Stichting European Society for Clinical Investigation Journal Foundation.

Irrelevance of microsatellite instability in the epidemiology of sporadic pancreatic ductal adenocarcinoma.

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Luigi Laghi

Full Text Available Pancreatic cancer risk is increased in Lynch syndrome (LS patients with mismatch repair gene defects predisposing to colonic and extracolonic cancers with microsatellite instability (MSI. However, the frequency of MSI pancreatic cancers has never been ascertained in consecutive, unselected clinical series, and their contribution to the sporadic and inherited burden of pancreatic cancer remains to be established. Aims of the study were to determine the prevalence of MSI in surgically resected pancreatic cancers in a multicentric, retrospective study, and to assess the occurrence of pancreatic cancer in LS.MS-status was screened by a panel of 5 mononucleotide repeats (Bat26, Bat25, NR-21, NR-24 and NR-27 in 338 consecutive pancreatic ductal adenocarcinoma (PDAC, resected at two Italian and one German referral centres. The personal history of pancreatic cancer was assessed in an independent set of 58 probands with LS and in 138 first degree relatives who had cancers.Only one PDAC (0.3% showed MSI. This was a medullary type cancer, with hMLH1-deficiency, and no identified germ-line mutation but methylation of hMLH1. Pancreatic cancer occurred in 5 (2.5% LS patients. Histological sampling was available for 2 cases, revealing PDAC in one case and an ampullary cancer in the other one.MSI prevalence is negligible in sporadic, resected PDAC. Differently, the prevalence of pancreatic cancer is 2.5% in LS patients, and cancers other than PDAC may be encountered in this setting. Surveillance for pancreatic cancer should be advised in LS mutation carriers at referral centers.

Curcumin synergizes with resveratrol to inhibit colon cancer.

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Majumdar, Adhip P N; Banerjee, Sanjeev; Nautiyal, Jyoti; Patel, Bhaumik B; Patel, Vaishali; Du, Jianhua; Yu, Yingjie; Elliott, Althea A; Levi, Edi; Sarkar, Fazlul H

2009-01-01

Development and progression of many malignancies, including colorectal cancer, are associated with activation of multiple signaling pathways. Therefore, inhibition of these signaling pathways with noncytotoxic natural products represents a logical preventive and/or therapeutic approach for colon cancer. Curcumin and resveratrol, both of which inhibit the growth of transformed cells and colon carcinogenesis, were selected to examine whether combining them would be an effective preventive and/or therapeutic strategy for colon cancer. Indeed, the combination of curcumin and resveratrol was found to be more effective in inhibiting growth of p53-positive (wt) and p53-negative colon cancer HCT-116 cells in vitro and in vivo in SCID xenografts of colon cancer HCT-116 (wt) cells than either agent alone. Analysis by Calcusyn software showed synergism between curcumin and resveratrol. The inhibition of tumors in response to curcumin and/or resveratrol was associated with the reduction in proliferation and stimulation of apoptosis accompanied by attenuation of NF-kappaB activity. In vitro studies have further demonstrated that the combinatorial treatment caused a greater inhibition of constitutive activation of EGFR and its family members as well as IGF-1R. Our current data suggest that the combination of curcumin and resveratrol could be an effective preventive/therapeutic strategy for colon cancer.

The Economics of Colon Cancer.

Science.gov (United States)

Orangio, Guy R

2018-04-01

The economic burden of cancer on the national health expenditure is billions of dollars. The economic cost is measured on direct and indirect medical costs, which vary depending on stage at diagnosis, patient age, type of medical services, and site of service. Costs vary by region, physician behavior, and patient preferences. When analyzing the economic burden of survivors of colon cancer, we cannot forget the societal burden. Post-acute care and readmissions are major economic burdens. People with colon cancer have to be followed for their lifetime. Economic models are being studied to give cost-effective solutions to this problem. Copyright © 2017 Elsevier Inc. All rights reserved.

Medullary colonic carcinoma with microsatellite instability has lower survival compared with conventional colonic adenocarcinoma with microsatellite instability

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Miguel A. Gómez-Álvarez

2016-12-01

Full Text Available Introduction: Colorectal medullary carcinoma (MC is a rare subtype of poorly differentiated adenocarcinoma (PDA with unclear prognostic significance. Microsatellite instable (MSI colorectal carcinomas have demonstrated better prognosis in clinical stage II. Aim: To analyze the survival and clinicopathological characteristics of MCs versus PDAs with MSI in clinical stage III. Material and methods: We studied 22 cases of PDAs with MSI versus 10 MCs. Results : Of the 10 MCs, 7 patients were men; the mean age was 57.8 ±5.6 years. The mean tumor size was 9.6 ±4.1 cm, and the primary site was the right colon in 9; 7 patients showed lymph node metastases (LNM and lymphovascular invasion (LVI. Of the 22 PDA cases, 12 (54.5% were women with a mean age of 75 ±16.1 years. The mean tumor size was 6.4 ±3.2 cm. Twelve (54.5% presented in the right colon, 21 (95.5% showed LNM and 7 (31.8% LVI. Follow-up was 32 ±8 months, with a 5-year overall survival of 42.9% for MCs and 76.6% for PDAs (p = 0.048. Univariate analysis found local recurrence (p = 0.001 and medullary subtype (p = 0.043 associated with lower survival. Conclusions : Medullary carcinomas were of greater tumor size and associated with more LVI and worse survival versus PDAs with MSI in stage III.

Clinicopathologic factors identify sporadic mismatch repair-defective colon cancers

DEFF Research Database (Denmark)

Halvarsson, Britta; Anderson, Harald; Domanska, Katarina

2008-01-01

Identification of sporadic mismatch repair (MMR)-defective colon cancers is increasingly demanded for decisions on adjuvant therapies. We evaluated clinicopathologic factors for the identification of these prognostically favorable tumors. Histopathologic features in 238 consecutive colon cancers...... and excluded 61.5% of the tumors from MMR testing. This clinicopathologic index thus successfully selects MMR-defective colon cancers. Udgivelsesdato: 2008-Feb...

Colon Cancer After Acute Diverticulitis Treatment

OpenAIRE

Oh, Kwang Hoon; Han, Koon Hee; Kim, Eun Jung; Lee, Je Hoon; Choi, Kyu Un; Han, Myung Sik; Ahn, Jae Hong; Cheon, Gab Jin

2013-01-01

Diverticulitis is the most common clinical complication of diverticular disease, affecting 10-25% of the patients with diverticula. The prevalences of diverticulitis and colon cancer tend to increase with age and are higher in industrialized countries. Consequently, diverticulitis and colon cancer have been reported to have similar epidemiological characteristics. However, the relationship between these diseases remains controversial, as is the performance of routine colonoscopy after an epis...

Prostate and Colon Cancer Screening Messages in Popular Magazines

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Katz, Mira L; Sheridan, Stacey; Pignone, Michael; Lewis, Carmen; Battle, Jamila; Gollop, Claudia; O'Malley, Michael

2004-01-01

OBJECTIVES To 1) compare the number of articles published about prostate, colon, and breast cancer in popular magazines during the past 2 decades, and 2) evaluate the content of in-depth prostate and colon cancer screening articles identified from 1996 to 2001. DESIGN We used a searchable database to identify the number of prostate, colon, and breast cancer articles published in three magazines with the highest circulation from six categories. In addition, we performed a systematic review on the in-depth (≥2 pages) articles on prostate and colon cancer screening that appeared from 1996 through 2001. RESULTS Although the number of magazine articles on prostate and colon cancer published in the 1990s increased compared to the 1980s, the number of articles is approximately one third of breast cancer articles. There were 36 in-depth articles from 1996 to 2001 in which prostate or colon cancer screening were mentioned. Over 90% of the articles recommended screening. However, of those articles, only 76% (25/33; 95% confidence interval [CI], 58% to 89%) cited screening guidelines. The benefits of screening were mentioned in 89% (32/36; 95% CI, 74% to 97%) but the harms were only found in 58% (21/36; 95% CI, 41% to 75%). Only 28% (10/36; 95% CI, 14% to 45%) of the articles provided all the necessary information needed for the reader to make an informed decision. CONCLUSIONS In-depth articles about prostate and colon cancer in popular magazines do not appear as frequently as articles about breast cancer. The available articles on prostate and colon cancer screening often do not provide the information necessary for the reader to make an informed decision about screening. PMID:15242469

Nutraceuticals as potential therapeutic agents for colon cancer: a review

Directory of Open Access Journals (Sweden)

Palaniselvam Kuppusamy

2014-06-01

Full Text Available Colon cancer is a world-wide health problem and the second-most dangerous type of cancer, affecting both men and women. The modern diet and lifestyles, with high meat consumption and excessive alcohol use, along with limited physical activity has led to an increasing mortality rate for colon cancer worldwide. As a result, there is a need to develop novel and environmentally benign drug therapies for colon cancer. Currently, nutraceuticals play an increasingly important role in the treatment of various chronic diseases such as colon cancer, diabetes and Alzheimer׳s disease. Nutraceuticals are derived from various natural sources such as medicinal plants, marine organisms, vegetables and fruits. Nutraceuticals have shown the potential to reduce the risk of colon cancer and slow its progression. These dietary substances target different molecular aspects of colon cancer development. Accordingly, this review briefly discusses the medicinal importance of nutraceuticals and their ability to reduce the risk of colorectal carcinogenesis.

Nutraceuticals as potential therapeutic agents for colon cancer: a review.

Science.gov (United States)

Kuppusamy, Palaniselvam; Yusoff, Mashitah M; Maniam, Gaanty Pragas; Ichwan, Solachuddin Jauhari Arief; Soundharrajan, Ilavenil; Govindan, Natanamurugaraj

2014-06-01

Colon cancer is a world-wide health problem and the second-most dangerous type of cancer, affecting both men and women. The modern diet and lifestyles, with high meat consumption and excessive alcohol use, along with limited physical activity has led to an increasing mortality rate for colon cancer worldwide. As a result, there is a need to develop novel and environmentally benign drug therapies for colon cancer. Currently, nutraceuticals play an increasingly important role in the treatment of various chronic diseases such as colon cancer, diabetes and Alzheimer׳s disease. Nutraceuticals are derived from various natural sources such as medicinal plants, marine organisms, vegetables and fruits. Nutraceuticals have shown the potential to reduce the risk of colon cancer and slow its progression. These dietary substances target different molecular aspects of colon cancer development. Accordingly, this review briefly discusses the medicinal importance of nutraceuticals and their ability to reduce the risk of colorectal carcinogenesis.

Differences in telomerase activity between colon and rectal cancer.

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Ayiomamitis, Georgios D; Notas, George; Zaravinos, Apostolos; Zizi-Sermpetzoglou, Adamantia; Georgiadou, Maria; Sfakianaki, Ourania; Kouroumallis, Elias

2014-06-01

Colorectal cancer is one of the most common cancers and the third leading cause of cancer death in both sexes. The disease progresses as a multistep process and is associated with genetic alterations. One of the characteristic features of cancer is telomerase activation. We sought to evaluate the differences in telomerase activity between colon cancer and adjacent normal tissue and to correlate the differences in telomerase activity between different locations with clinicopathological factors and survival. Matched colon tumour samples and adjacent normal mucosa samples 10 cm away from the tumour were collected during colectomy. We assessed telomerase activity using real time polymerase chain reaction. Several pathological characteristics of tumours, including p53, Ki-67, p21, bcl2 and MLH1 expression were also studied. We collected samples from 49 patients. There was a significantly higher telomerase activity in colon cancer tissue than normal tissue. Adenocarcinomas of the right colon express significantly higher telomerase than left-side cancers. Colon cancers and their adjacent normal tissue had significantly more telomerase and were more positive to MLH1 than rectal cancers. The expression of p53 negatively correlated to telomerase activity and was linked to better patient survival. Colon and rectal cancers seem to have different telomerase and MLH1 profiles, and this could be another factor for their different biologic and clinical behaviour and progression. These results support the idea that the large bowel cannot be considered a uniform organ, at least in the biology of cancer.

A Study of Clinicopathological Differences Between Right-sided and Left-sided Colon Cancers

OpenAIRE

芳賀, 駿介; 遠藤, 俊吾; 加藤, 博之; 高橋, 直樹; 吉松, 和彦; 橋本, 雅彦; 石橋, 敬一郎; 梅原, 有弘; 横溝, 肇; 梶原, 哲郎; Shunsuke, HAGA; Shungo, ENDO; Hiroyuki, KATO; Naoki, TAKAHASHI; Kazuhiko, YOSHIMATSU

1996-01-01

The present study was aimed to determine the clinicopathological features of cancers of the right-sided colon (cecum, ascending colon, transverse colon) and left-sided colon (descending colon, sigmoid colon) in order to help improve the efficacy of their treatment. Excluding multiple cancer cases, 364 patients with primary colon cancer underwent surgey at our department between 1974 and 1994; they comprised 171 individuals with right-sided colon cancer and 193 with left-sided colon cancer. A ...

Differences in survival between colon and rectal cancer from SEER data.

Science.gov (United States)

Lee, Yen-Chien; Lee, Yen-Lin; Chuang, Jen-Pin; Lee, Jenq-Chang

2013-01-01

Little is known about colorectal cancer or colon and rectal cancer. Are they the same disease or different diseases? The aim of this epidemiology study was to compare the features of colon and rectal cancer by using recent national cancer surveillance data. Data included colorectal cancer (1995-2008) from the Surveillance, Epidemiology, and End Results Program (SEER) database. Only adenocarcinoma was included for analysis. A total of 372,130 patients with a median follow-up of 32 months were analyzed. Mean survival of patients with the same stage of colon and rectal cancer was evaluated. Around 35% of patients had stage information. Among them, colon cancer patients had better survival than those with rectal cancer, by a margin of 4 months in stage IIB. In stage IIIC and stage IV, rectal cancer patients had better survival than colon cancer patients, by about 3 months. Stage IIB colorectal cancer patients had a poorer prognosis than those with stage IIIA and IIIB colorectal cancer. After adjustment of age, sex and race, colon cancer patients had better survival than rectal cancer of stage IIB, but in stage IIIC and IV, rectal cancer patients had better survival than colon cancer. The study is limited by its retrospective nature. This was a population-based study. The prognosis of rectal cancer was not worse than that of colon cancer. Local advanced colorectal cancer had a poorer prognosis than local regional lymph node metastasis. Stage IIB might require more aggressive chemotherapy, and no less than that for stage III.

Increased Expression and Aberrant Localization of Mucin 13 in Metastatic Colon Cancer

Science.gov (United States)

Gupta, Brij K.; Maher, Diane M.; Ebeling, Mara C.; Sundram, Vasudha; Koch, Michael D.; Lynch, Douglas W.; Bohlmeyer, Teresa; Watanabe, Akira; Aburatani, Hiroyuki; Puumala, Susan E.; Jaggi, Meena

2012-01-01

MUC13 is a newly identified transmembrane mucin. Although MUC13 is known to be overexpressed in ovarian and gastric cancers, limited information is available regarding the expression of MUC13 in metastatic colon cancer. Herein, we investigated the expression profile of MUC13 in colon cancer using a novel anti-MUC13 monoclonal antibody (MAb, clone ppz0020) by immunohistochemical (IHC) analysis. A cohort of colon cancer samples and tissue microarrays containing adjacent normal, non-metastatic colon cancer, metastatic colon cancer, and liver metastasis tissues was used in this study to investigate the expression pattern of MUC13. IHC analysis revealed significantly higher (pcolon cancer samples compared with faint or very low expression in adjacent normal tissues. Interestingly, metastatic colon cancer and liver metastasis tissue samples demonstrated significantly (pcolon cancer and adjacent normal colon samples. Moreover, cytoplasmic and nuclear MUC13 expression correlated with larger and poorly differentiated tumors. Four of six tested colon cancer cell lines also expressed MUC13 at RNA and protein levels. These studies demonstrate a significant increase in MUC13 expression in metastatic colon cancer and suggest a correlation between aberrant MUC13 localization (cytoplasmic and nuclear expression) and metastatic colon cancer. PMID:22914648

Ezrin expression combined with MSI status in prognostication of stage II colorectal cancer.

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Khadija Slik

Full Text Available Currently used factors predicting disease recurrence in stage II colorectal cancer patients are not optimal for risk stratification. Thus, new biomarkers are needed. In this study the applicability of ezrin protein expression together with MSI status and BRAF mutation status were tested in predicting disease outcome in stage II colorectal cancer. The study population consisted of 173 stage II colorectal cancer patients. Paraffin-embedded cancer tissue material from surgical specimens was used to construct tissue microarrays (TMAs with next-generation technique. The TMA-slides were subjected to following immunohistochemical stainings: MLH1, MSH2, MSH6, PMS2, ezrin and anti-BRAF V600E antibody. The staining results were correlated with clinicopathological variables and survival. In categorical analysis, high ezrin protein expression correlated with poor disease-specific survival (p = 0.038. In univariate analysis patients having microsatellite instabile / low ezrin expression tumors had a significantly longer disease-specific survival than patients having microsatellite stable / high ezrin expression tumors (p = 0.007. In multivariate survival analysis, the presence of BRAF mutation was associated to poor overall survival (p = 0.028, HR 3.29, 95% CI1.14-9.54. High ezrin protein expression in patients with microsatellite stable tumors was linked to poor disease-specific survival (p = 0.01, HR 5.68, 95% CI 1.53-21.12. Ezrin protein expression is a promising biomarker in estimating the outcome of stage II colorectal cancer patients. When combined with microsatellite status its ability in predicting disease outcome is further improved.

Is There a Proximal Migration of Colon Cancers? An Experience from Regional Cancer Center

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Gouda YG

2016-01-01

Full Text Available Colorectal cancers stands 3rd in males and 2nd in females in order of frequency of most common cancers worldwide and in developed countries. And is 4th common in males and 5th common in females in developing countries. Colonic tumors located at the caecum, ascending colon, hepatic flexure, transverse colon, and splenic flexure were defined as right sided colon cancer and tumors located at the descending colon, sigmoid, rectosigmoid and rectum were defined as left sided colorectal cancer. The difference in percentage deviation is statistically not significant and present study concludes that there is no actual migration of colon cancers towards right side. In the present study there is higher proportion of males being affected with Right colon cancers group which is significant and doesn’t go in accordance with the literature published, where females are more affected. Since this is institutional based study there is further need for studies based on population. As the mean age at presentation was very earlier than in the developed countries, the thrust is in us to have an effective screening programs.

Improvements in 5-year outcomes of stage II/III rectal cancer relative to colon cancer.

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Renouf, Daniel J; Woods, Ryan; Speers, Caroline; Hay, John; Phang, P Terry; Fitzgerald, Catherine; Kennecke, Hagen

2013-12-01

Stage for stage, rectal cancer has historically been associated with inferior survival compared with colon cancer. Randomized trials of rectal cancer have generally demonstrated improvements in locoregional relapse but not survival. We compared therapy and outcomes of colon versus rectal cancer in 2 time cohorts to determine if relative improvements have occurred. Patients with resected stage II/III colorectal cancer referred to the British Columbia Cancer Agency in 1989/1990 and 2001/2002 were identified. The higher of clinical or pathologic stage was used for patients receiving preoperative chemoradiation. Disease-specific survival (DSS) and overall survival (OS) were compared for rectal and colon cancer between the 2 cohorts. Kaplan-Meier method was used for survival analysis. A total of 1427 patients were included, with 375 from 1989/1990 and 1052 from 2001/2002. Between 1989/1990 and 2001/2002 there were significant increases in the use of perioperative chemotherapy for both rectal and colon cancer (Prectal cancer. DSS significantly improved for rectal (Pcolon cancer (P=0.069). Five-year OS was significantly inferior for rectal versus colon cancer in 1989/1990 (46.1% vs. 57.2%, P=0.023) and was similar to that of colon cancer in 2001/2002 (63.7% vs. 66.2%, P=0.454). Advances in locoregional and systemic therapy significantly improved survival among patients with rectal cancer. DSS and OS are now similar between colon and rectal cancer for both stage II and III disease.

Colon cancer chemoprevention with ginseng and other botanicals.

OpenAIRE

Wargovich, M J

2001-01-01

Colorectal cancer is becoming increasingly common in Asian countries and still remains the second leading cause of cancer deaths in the United States. Efforts to prevent colon cancer have targeted early detection through screening and chemoprevention. For the last ten years our laboratory has utilized an in vivo screening assay for the testing of potential cancer preventives for colon cancer. We have conducted investigations on over 150 compounds including many with botanical or herbal origin...

Treatment of colon cancer with oncolytic herpes simplex virus in preclinical models.

Science.gov (United States)

Yang, H; Peng, T; Li, J; Wang, Y; Zhang, W; Zhang, P; Peng, S; Du, T; Li, Y; Yan, Q; Liu, B

2016-05-01

Cancer stem cells (CSCs), which are a rare population in any type of cancer, including colon cancer, are tumorigenic and responsible for cancer recurrence and metastasis. CSCs have been isolated from a number of different solid tumors recently, although the isolation of CSCs in colon cancer is still challenging. We cultured colon cancer cells in stem cell medium to obtain colonosphere cells. These cells possessed the characteristics of CSCs, with a high capacity of tumorigenicity, migration and invasion in vitro and in vivo. The isolation and identification of CSCs have provided new targets for the therapeutics. Oncolytic herpes simplex viruses (oHSV) are an effective strategy for killing colon cancer cells in preclinical models. Here, we examined the efficacy of an oncolytic herpes simplex virus type 2 (oHSV2) in killing colon cancer cells and colon cancer stem-like cells (CSLCs). oHSV2 was found to be highly cytotoxic to the adherent and sphere cells in vitro, and oHSV2 treatment in vivo significantly inhibited tumor growth. This study demonstrates that oHSV2 is effective against colon cancer cells and colon CSLCs and could be a promising strategy for treating colon cancer patients.

Colon Cancer Chemoprevention by Sage Tea Drinking: Decreased DNA Damage and Cell Proliferation.

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Pedro, Dalila F N; Ramos, Alice A; Lima, Cristovao F; Baltazar, Fatima; Pereira-Wilson, Cristina

2016-02-01

Salvia officinalis and some of its isolated compounds have been found to be preventive of DNA damage and increased proliferation in vitro in colon cells. In the present study, we used the azoxymethane model to test effects of S. officinalis on colon cancer prevention in vivo. The results showed that sage treatment reduced the number of ACF formed only if administered before azoxymethane injection, demonstrating that sage tea drinking has a chemopreventive effect on colorectal cancer. A decrease in the proliferation marker Ki67 and in H2 O2 -induced and azoxymethane-induced DNA damage to colonocytes and lymphocytes were found with sage treatment. This confirms in vivo the chemopreventive effects of S. officinalis. Taken together, our results show that sage treatment prevented initiation phases of colon carcinogenesis, an effect due, at least in part, to DNA protection, and reduced proliferation rates of colon epithelial cell that prevent mutations and their fixation through cell replication. These chemopreventive effects of S. officinalis on colon cancer add to the many health benefits attributed to sage and encourage its consumption. Copyright © 2015 John Wiley & Sons, Ltd.

Occlusive stenosis – atypical presentation of right colon cancer

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Petrişor Banu

2018-05-01

Full Text Available Colorectal cancers are one of the most frequent malignancies worldwide. Significant differences are described in relation to the location of tumors within the colon. Thus, between right and left colon cancer there are epidemiological, clinical, genetic, evolutionary and prognostic differences. Considering these premises, right and left colon cancers can be seen as distinct pathological entities. In right colon cancer the initial phases are often asymptomatic and the presence of symptoms is in relation to advanced phases and complications. We report the case of a 64-year-old man with no significant medical history who was admitted and operated as an emergency for stenotic and perforated tumor of the right colon. Operative exploration revealed distended small bowel loops and caecum up to the ascending colon where a stenosing tumor is found. The tumor extends to a small bowel loop and also exhibit a perforation. Right hemicolectomy was performed, with favorable postoperative evolution and discharge on 7th day.

Differences in survival between colon and rectal cancer from SEER data.

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Yen-Chien Lee

Full Text Available BACKGROUND: Little is known about colorectal cancer or colon and rectal cancer. Are they the same disease or different diseases? OBJECTIVES: The aim of this epidemiology study was to compare the features of colon and rectal cancer by using recent national cancer surveillance data. DESIGN AND SETTING: Data included colorectal cancer (1995-2008 from the Surveillance, Epidemiology, and End Results Program (SEER database. Only adenocarcinoma was included for analysis. PATIENTS: A total of 372,130 patients with a median follow-up of 32 months were analyzed. MAIN OUTCOME MEASURES: Mean survival of patients with the same stage of colon and rectal cancer was evaluated. RESULTS: Around 35% of patients had stage information. Among them, colon cancer patients had better survival than those with rectal cancer, by a margin of 4 months in stage IIB. In stage IIIC and stage IV, rectal cancer patients had better survival than colon cancer patients, by about 3 months. Stage IIB colorectal cancer patients had a poorer prognosis than those with stage IIIA and IIIB colorectal cancer. After adjustment of age, sex and race, colon cancer patients had better survival than rectal cancer of stage IIB, but in stage IIIC and IV, rectal cancer patients had better survival than colon cancer. LIMITATIONS: The study is limited by its retrospective nature. CONCLUSION: This was a population-based study. The prognosis of rectal cancer was not worse than that of colon cancer. Local advanced colorectal cancer had a poorer prognosis than local regional lymph node metastasis. Stage IIB might require more aggressive chemotherapy, and no less than that for stage III.

Chemoresistance of CD133{sup +} colon cancer may be related with increased survivin expression

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Lee, Mi-Ra; Ji, Sun-Young; Mia-Jan, Khalilullah [Department of Pathology, Yonsei University, Wonju College of Medicine, Wonju (Korea, Republic of); Cho, Mee-Yon, E-mail: meeyon@yonsei.ac.kr [Department of Pathology, Yonsei University, Wonju College of Medicine, Wonju (Korea, Republic of); Institute of Genomic Cohort, Yonsei University, Wonju College of Medicine, Wonju (Korea, Republic of)

2015-07-31

CD133, putative cancer stem cell marker, deemed to aid chemoresistance. However, this claim has been challenged recently and we previously reported that patients with CD133{sup +} colon cancer have benefit from 5-fluorouracil (5-FU) chemotherapy incontrast to no benefit in patients with CD133{sup −} cancer. To elucidate the role of CD133 expression in chemoresistance, we silenced the CD133 expression in a colon cancer cell line and determined its effect on the biological characteristics downstream. We comparatively analyzed the sequential changes of MDR1, ABCG2, AKT1 and survivin expression and the result of proliferation assay (WST-1 assay) with 5-FU treatment in CD133{sup +} and siRNA-induced CD133{sup −} cells, derived from Caco-2 colon cancer cell line. 5-FU treatment induced significantly increase of the mRNA expression of MDR1, ABCG2 and AKT1genes, but not protein level. CD133 had little to no effect on the mRNA and protein expression of these genes. However, survivin expression at mRNA and protein level were significantly increased in CD133{sup +} cells compared with siRNA-induced CD133-cells and Mock (not sorted CD133{sup +} cells) at 96 h after siRNA transfection. The cytotoxicity assay demonstrated notable increase of chemoresistance to 5-FU treatment (10 μM) in CD133{sup +} cells at 96 h after siRNA transfection. From this study, we conclude that CD133{sup +} cells may have chemoresistance to 5-FU through the mechanism which is related with survivin expression, instead of MDR1, ABCG2 and AKT1 expression. Therefore a survivin inhibitor can be a new target for effective treatment of CD133{sup +} colon cancer. - Highlights: • We evaluate the role of CD133 in chemoresistance of colon cancer. • We compared the chemoresistance of CD133{sup +} cells and siRNA-induced CD133{sup −} cells. • CD133 had little to no effect on MDR1, ABCG2 and AKT1 expression. • Survivin expression and chemoresistance were increased in CD133{sup +} colon cancer cells.

EMT is the dominant program in human colon cancer

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Tollenaar Rob AEM

2011-01-01

Full Text Available Abstract Background Colon cancer has been classically described by clinicopathologic features that permit the prediction of outcome only after surgical resection and staging. Methods We performed an unsupervised analysis of microarray data from 326 colon cancers to identify the first principal component (PC1 of the most variable set of genes. PC1 deciphered two primary, intrinsic molecular subtypes of colon cancer that predicted disease progression and recurrence. Results Here we report that the most dominant pattern of intrinsic gene expression in colon cancer (PC1 was tightly correlated (Pearson R = 0.92, P -135 with the EMT signature-- both in gene identity and directionality. In a global micro-RNA screen, we further identified the most anti-correlated microRNA with PC1 as MiR200, known to regulate EMT. Conclusions These data demonstrate that the biology underpinning the native, molecular classification of human colon cancer--previously thought to be highly heterogeneous-- was clarified through the lens of comprehensive transcriptome analysis.

Rectal and colon cancer: Not just a different anatomic site.

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Tamas, K; Walenkamp, A M E; de Vries, E G E; van Vugt, M A T M; Beets-Tan, R G; van Etten, B; de Groot, D J A; Hospers, G A P

2015-09-01

Due to differences in anatomy, primary rectal and colon cancer require different staging procedures, different neo-adjuvant treatment and different surgical approaches. For example, neoadjuvant radiotherapy or chemoradiotherapy is administered solely for rectal cancer. Neoadjuvant therapy and total mesorectal excision for rectal cancer might be responsible in part for the differing effect of adjuvant systemic treatment on overall survival, which is more evident in colon cancer than in rectal cancer. Apart from anatomic divergences, rectal and colon cancer also differ in their embryological origin and metastatic patterns. Moreover, they harbor a different composition of drug targets, such as v-raf murine sarcoma viral oncogene homolog B (BRAF), which is preferentially mutated in proximal colon cancers, and the epidermal growth factor receptor (EGFR), which is prevalently amplified or overexpressed in distal colorectal cancers. Despite their differences in metastatic pattern, composition of drug targets and earlier local treatment, metastatic rectal and colon cancer are, however, commonly regarded as one entity and are treated alike. In this review, we focused on rectal cancer and its biological and clinical differences and similarities relative to colon cancer. These aspects are crucial because they influence the current staging and treatment of these cancers, and might influence the design of future trials with targeted drugs. Copyright © 2015 Elsevier Ltd. All rights reserved.

Potentialities of computed tomography and ultrasonography in colonic cancer

International Nuclear Information System (INIS)

Gorshkov, A.N.

2001-01-01

Data of examination of 59 patients with colonic cancer were used to consider the potentialities of transabdominal, transrectal ultrasonography and X-ay compound tomography and to assess their value in diagnosing colonic cancer, including its minor forms. Ultrasound and computed tomographic semiotics of colonic cancer and determines a place of the above techniques in the algorithm of radiation and instrumental studies are described. Inclusion of these techniques into the diagnostic algorithm may solve a range of differentially diagnostic problems and allows a preliminary analysis to be made in a tumor lesion according to the International TNM classification. Ultrasonography and X-ray computed tomography should be included into a range of basic methods for diagnosis of colonic cancer [ru

CacyBP/SIP promotes the proliferation of colon cancer cells.

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Huihong Zhai

Full Text Available CacyBP/SIP is a component of the ubiquitin pathway and is overexpressed in several transformed tumor tissues, including colon cancer, which is one of the most common cancers worldwide. It is unknown whether CacyBP/SIP promotes the proliferation of colon cancer cells. This study examined the expression level, subcellular localization, and binding activity of CacyBP/SIP in human colon cancer cells in the presence and absence of the hormone gastrin. We found that CacyBP/SIP was expressed in a high percentage of colon cancer cells, but not in normal colonic surface epithelium. CacyBP/SIP promoted the cell proliferation of colon cancer cells under both basal and gastrin stimulated conditions as shown by knockdown studies. Gastrin stimulation triggered the translocation of CacyBP/SIP to the nucleus, and enhanced interaction between CacyBP/SIP and SKP1, a key component of ubiquitination pathway which further mediated the proteasome-dependent degradation of p27kip1 protein. The gastrin induced reduction in p27kip1 was prevented when cells were treated with the proteasome inhibitor MG132. These results suggest that CacyBP/SIP may be promoting growth of colon cancer cells by enhancing ubiquitin-mediated degradation of p27kip1.

Mechanisms of oncogenesis in colon versus rectal cancer.

NARCIS (Netherlands)

Kapiteijn, E.; Liefers, G.J.; Los, L.C.; Meershoek-Klein Kranenbarg, E.; Hermans, J.; Tollenaar, R.A.E.M.; Moriya, Y.; Veld, C.J.H. van de; Krieken, J.H.J.M. van

2001-01-01

Observations support the theory that development of left- and right-sided colorectal cancers may involve different mechanisms. This study investigated different genes involved in oncogenesis of colon and rectal cancers and analysed their prognostic value. The study group comprised 35 colon and 42

IFNγ induces DNA methylation-silenced GPR109A expression via pSTAT1/p300 and H3K18 acetylation in colon cancer

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Bardhan, Kankana; Paschall, Amy V.; Yang, Dafeng; Chen, May R.; Simon, Priscilla S.; Bhutia, Yangzom; Martin, Pamela M.; Thangaraju, Muthusamy; Browning, Darren D.; Ganapathy, Vadivel; Heaton, Christopher M.; Gu, Keni; Lee, Jeffrey R.; Liu, Kebin

2015-01-01

Short-chain fatty acids, metabolites produced by colonic microbiota from fermentation of dietary fiber, act as anti-inflammatory agents in the intestinal tract to suppress proinflammatory diseases. GPR109A is the receptor for short-chain fatty acids. The functions of GPR109A has been the subject of extensive studies, however, the molecular mechanisms underlying GPR109A expression is largely unknown. We show that GPR109A is highly expressed in normal human colon tissues, but is silenced in human colon carcinoma cells. The GPR109A promoter DNA is methylated in human colon carcinoma. Strikingly, we observed that IFNγ, a cytokine secreted by activated T cells, activates GPR109A transcription without altering its promoter DNA methylation. Colon carcinoma grows significantly faster in IFNγ-deficient mice than in wildtype mice in an orthotopic colon cancer mouse model. A positive correlation was observed between GPR109A protein level and tumor-infiltrating T cells in human colon carcinoma specimens, and IFNγ expression level is higher in human colon carcinoma tissues than in normal colon tissues. We further demonstrated that IFNγ rapidly activates pSTAT1 that binds to the promoter of p300 to activate its transcription. p300 then binds to the GPR109A promoters to induce H3K18 hyperacetylation, resulting in chromatin remodeling in the methylated GPR109A promoter. The IFNγ-activated pSTAT1 then directly binds to the methylated but hyperacetylated GPR109 promoters to activate its transcription. Overall, our data indicate that GPR109A acts as a tumor suppressor in colon cancer and the host immune system might use IFNγ to counteract DNA methylation-mediated GPR109A silencing as a mechanism to suppress tumor development. PMID:25735954

Chemoresistance of CD133(+) colon cancer may be related with increased survivin expression.

Science.gov (United States)

Lee, Mi-Ra; Ji, Sun-Young; Mia-Jan, Khalilullah; Cho, Mee-Yon

2015-07-31

CD133, putative cancer stem cell marker, deemed to aid chemoresistance. However, this claim has been challenged recently and we previously reported that patients with CD133(+) colon cancer have benefit from 5-fluorouracil (5-FU) chemotherapy incontrast to no benefit in patients with CD133(-) cancer. To elucidate the role of CD133 expression in chemoresistance, we silenced the CD133 expression in a colon cancer cell line and determined its effect on the biological characteristics downstream. We comparatively analyzed the sequential changes of MDR1, ABCG2, AKT1 and survivin expression and the result of proliferation assay (WST-1 assay) with 5-FU treatment in CD133(+) and siRNA-induced CD133(-) cells, derived from Caco-2 colon cancer cell line. 5-FU treatment induced significantly increase of the mRNA expression of MDR1, ABCG2 and AKT1genes, but not protein level. CD133 had little to no effect on the mRNA and protein expression of these genes. However, survivin expression at mRNA and protein level were significantly increased in CD133(+) cells compared with siRNA-induced CD133-cells and Mock (not sorted CD133(+) cells) at 96 h after siRNA transfection. The cytotoxicity assay demonstrated notable increase of chemoresistance to 5-FU treatment (10 μM) in CD133(+) cells at 96 h after siRNA transfection. From this study, we conclude that CD133(+) cells may have chemoresistance to 5-FU through the mechanism which is related with survivin expression, instead of MDR1, ABCG2 and AKT1 expression. Therefore a survivin inhibitor can be a new target for effective treatment of CD133(+) colon cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

Transverse colon cancer with Krukenberg tumor : A case report

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東門, 敦子; 松原, 洋孝; 下地, 英明; 伊佐, 勉; 濱安, 俊吾; 仲地, 厚; 宮里, 浩; 白石, 祐之; 武藤, 良弘; Tomon, Atsuko; Matsubara, Hirotaka; Shimoji, Hideaki; Isa, Tsutomu; Nakachi, Atsushi; Miyazato, Hiroshi

1999-01-01

A case of Krukenberg tumor in a 30-year-old woman with transverse colon cancer is reported herein. The patient was found to have bilateral ovarian tumors and abnormal elevation of serum CEA at a community hospital. Subsequently, she was referred to the University Hospital for further work. Diagnostic examinations including US, CT and colonoscopy demonstrated transverse colon cancer and bilateral ovarian tumors. Exploratory laparotomy showed the growth of transverse colon cancer over the perit...

Impact of diabetes on oncologic outcome of colorectal cancer patients: colon vs. rectal cancer.

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Justin Y Jeon

Full Text Available BACKGROUND: To evaluate the impact of diabetes on outcomes in colorectal cancer patients and to examine whether this association varies by the location of tumor (colon vs. rectum. PATIENTS AND METHODS: This study includes 4,131 stage I-III colorectal cancer patients, treated between 1995 and 2007 (12.5% diabetic, 53% colon, 47% rectal in South Korea. Cox proportional hazards modeling was used to determine the prognostic influence of DM on survival endpoints. RESULTS: Colorectal cancer patients with DM had significantly worse disease-free survival (DFS [hazard ratio (HR 1.17, 95% confidence interval (CI: 1.00-1.37] compared with patients without DM. When considering colon and rectal cancer independently, DM was significantly associated with worse overall survival (OS (HR: 1.46, 95% CI: 1.11-1.92, DFS (HR: 1.45, 95% CI: 1.15-1.84 and recurrence-free survival (RFS (HR: 1.32, 95% CI: 0.98-1.76 in colon cancer patients. No association for OS, DFS or RFS was observed in rectal cancer patients. There was significant interaction of location of tumor (colon vs. rectal cancer with DM on OS (P = 0.009 and DFS (P = 0.007. CONCLUSIONS: This study suggests that DM negatively impacts survival outcomes of patients with colon cancer but not rectal cancer.

Local staging of sigmoid colon cancer using MRI

DEFF Research Database (Denmark)

Dam, Claus; Lindebjerg, Jan; Jakobsen, Anders

2017-01-01

BACKGROUND: An accurate radiological staging of colon cancer is crucial to select patients who may benefit from neoadjuvant chemotherapy. PURPOSE: To evaluate the diagnostic accuracy of preoperative magnetic resonance imaging (MRI) in identifying locally advanced sigmoid colon cancer, poor...... prognostic factors, and the inter-observer variation of the tumor apparent diffusion coefficient (ADC) values of diffusion-weighted imaging (DWI). MATERIAL AND METHODS: Using 1.5 T MRI with high resolution T2-weighted (T2W) imaging, DWI, and no contrast enhancement, 35 patients with sigmoid colon cancer were...... the measured mean ADC values were below 1.0 × 10(-3) mm(2)/s with an intra-class correlation coefficient in T3cd-T4 tumors of 0.85. CONCLUSION: Preoperative MRI can identify locally advanced sigmoid colon cancer and has potential as the imaging of choice to select patients for neoadjuvant chemotherapy. Initial...

Up-regulation of CNDP2 facilitates the proliferation of colon cancer.

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Xue, Conglong; Zhang, Zhenwei; Yu, Honglan; Yu, Miao; Yuan, Kaitao; Yang, Ting; Miao, Mingyong; Shi, Hanping

2014-05-21

Cytosolic nonspecific dipetidase (CN2) belongs to the family of M20 metallopeptidases. It was stated in previous articles that higher expression levels of CN2 were observed in renal cell carcinoma and breast cancer. Our study explored the correlation between CN2 and colon carcinogenesis. We analysed the relationship between 183 patients clinicopathological characteristics and its CN2 expression. To detect the levels of CN2 in colon cancer cell lines and colon cancer tissues by western blot. To verify cell proliferation in colon cancer cells with knockdown of CNDP2 and explore the causes of these phenomena. The expression levels of CN2 in clinical colon tumors and colon cancer cell lines were significantly higher than that in normal colon mucosa and colon cell lines. The difference in CN2 levels was associated with tumor location (right- and left-sided colon cancer), but there was no significant association with age, gender, tumor size, tumor grade, tumor stage or serum carcinoembryonic antigen (CEA). Knockdown of CNDP2 inhibited cell proliferation, blocked cell cycle progression and retarded carcinogenesis in an animal model. The signaling pathway through which knockdown of CNDP2 inhibited cell proliferation and tumorigenesis involved in EGFR, cyclin B1 and cyclin E. Knockdown of CNDP2 can inhibit the proliferation of colon cancer in vitro and retarded carcinogenesis in vivo.

Prevalence of Lynch syndrome in a Middle Eastern population with colorectal cancer.

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Siraj, Abdul K; Prabhakaran, Sarita; Bavi, Prashant; Bu, Rong; Beg, Shaham; Hazmi, Mohsen Al; Al-Rasheed, Maha; Al-Assiri, Mohammed; Sairafi, Rami; Al-Dayel, Fouad; Al-Sanea, Nasser; Uddin, Shahab; Al-Kuraya, Khawla S

2015-06-01

Lynch syndrome (LS; hereditary nonpolyposis colorectal cancer) is a common cause of hereditary colorectal cancer (CRC). CRC is the most common cancer diagnosed among males in Saudi Arabia but to the authors' knowledge there is a lack of data regarding the prevalence of LS in patients with CRC. There currently are no clear guidelines for the selection criteria for these patients to screen for LS. A comprehensive molecular characterization was performed in a cohort of 807 CRC cases by immunohistochemical and microsatellite analysis using polymerase chain reaction. BRAF mutation screening, high CpG island methylator phenotype, and analysis for germline mutations were performed in 425 CRC samples. These were all high microsatellite instability (MSI-H) samples (91 cases), all low MSI samples (143 cases), and selected cases from the microsatellite stable group (191 cases) that met revised Bethesda guidelines. Polymerase chain reaction identified 91 MSI-H cases (11.3%) and sequencing revealed mismatch repair germline mutations in 8 CRC cases only. Of the total of 807 CRC cases, these 8 cases (0.99%) were MSI-H, met the revised Bethesda guidelines, and did not harbor BRAF mutations. The results of the current study confirmed cases of LS in approximately 1.0% of CRC samples and reflects the efficacy of screening among MSI-H cases that lack BRAF mutations. This comprehensive study from Saudi Arabia will help in implementing a universal screening/reflex testing strategy in a clinical setting in Saudi Arabia and in conducting a national screening program that benefits both patients and their relatives. © 2015 American Cancer Society.

Colon cancer modulation by a diabetic environment: A single institutional experience.

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Prieto, Isabel; Del Puerto-Nevado, Laura; Gonzalez, Nieves; Portal-Nuñez, Sergio; Zazo, Sandra; Corton, Marta; Minguez, Pablo; Gomez-Guerrero, Carmen; Arce, Jose Miguel; Sanz, Ana Belen; Mas, Sebastian; Aguilera, Oscar; Alvarez-Llamas, Gloria; Esbrit, Pedro; Ortiz, Alberto; Ayuso, Carmen; Egido, Jesus; Rojo, Federico; Garcia-Foncillas, Jesus

2017-01-01

Multiple observational studies suggest an increased risk of colon cancer in patients with diabetes mellitus (DM). This can theoretically be the result of an influence of the diabetic environment on carcinogenesis or the tumor biologic behavior. To gain insight into the influence of a diabetic environment on colon cancer characteristics and outcomes. Retrospective analysis of clinical records in an academic tertiary care hospital with detailed analysis of 81 diabetic patients diagnosed of colon cancer matched with 79 non-diabetic colon cancer patients. The impact of streptozotocin-induced diabetes on the growth of colon cancer xenografts was studied in mice. The incidence of DM in 1,137 patients with colorectal cancer was 16%. The diabetic colon cancer cases and non-diabetic colon cancer controls were well matched for demographic and clinical variables. The ECOG Scale Performance Status was higher (worse) in diabetics (ECOG ≥1, 29.1% of controls vs 46.9% of diabetics, p = 0.02), but no significant differences were observed in tumor grade, adjuvant therapy, tumor site, lymphovascular invasion, stage, recurrence, death or cancer-related death. Moreover, no differences in tumor variables were observed between patients treated or not with metformin. In the xenograft model, tumor growth and histopathological characteristics did not differ between diabetic and nondiabetic animals. Our findings point towards a mild or negligible effect of the diabetes environment on colon cancer behavior, once cancer has already developed.

Multifaceted Interpretation of Colon Cancer Stem Cells.

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Hatano, Yuichiro; Fukuda, Shinya; Hisamatsu, Kenji; Hirata, Akihiro; Hara, Akira; Tomita, Hiroyuki

2017-07-05

Colon cancer is one of the leading causes of cancer-related deaths worldwide, despite recent advances in clinical oncology. Accumulating evidence sheds light on the existence of cancer stem cells and their role in conferring therapeutic resistance. Cancer stem cells are a minor fraction of cancer cells, which enable tumor heterogeneity and initiate tumor formation. In addition, these cells are resistant to various cytotoxic factors. Therefore, elimination of cancer stem cells is difficult but essential to cure the malignant foci completely. Herein, we review the recent evidence for intestinal stem cells and colon cancer stem cells, methods to detect the tumor-initiating cells, and clinical significance of cancer stem cell markers. We also describe the emerging problems of cancer stem cell theory, including bidirectional conversion and intertumoral heterogeneity of stem cell phenotype.

No association of CpG island methylator phenotype and colorectal cancer survival: population-based study.

Science.gov (United States)

Jia, Min; Jansen, Lina; Walter, Viola; Tagscherer, Katrin; Roth, Wilfried; Herpel, Esther; Kloor, Matthias; Bläker, Hendrik; Chang-Claude, Jenny; Brenner, Hermann; Hoffmeister, Michael

2016-11-22

Previous studies have shown adverse effects of CpG island methylator phenotype (CIMP) on colorectal cancer (CRC) prognosis. However, sample sizes were often limited and only few studies were able to adjust for relevant molecular features associated with CIMP. The aim of this study was to investigate the impact of CIMP on CRC survival in a large population-based study with comprehensive adjustment. The CIMP status and other molecular tumour features were analysed in 1385 CRC patients diagnosed between 2003 and 2010. Detailed information were obtained from standardised personal interviews and medical records. During follow-up (median: 4.9 years), we assessed vital status, cause of death and therapy details. Cox proportional hazard regression models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of survival after CRC. The CIMP-H occurred more frequently in patients with older age, female gender, cancer in the proximal colon, BRAF mutation and microsatellite instability-high (MSI-H). However, CIMP status was not associated with CRC prognosis in CRC patients (HR=1.00; 95% CI=0.72-1.40 for overall survival; HR=0.96; 95% CI=0.65-1.41 for disease-specific survival) or in any of the subgroups. Although CIMP status was associated with the presence of MSI-H and BRAF mutation, the prognostic effects of MSI-H (HR=0.49; 95% CI=0.27-0.90) and BRAF mutation (HR=1.78; 95% CI=1.10-2.84) were independent of CIMP status. Similar benefit of chemotherapy was found for CRC outcomes in both the CIMP-low/negative group and the CIMP-high group. CpG island methylator phenotype was not associated with CRC prognosis after adjusting for other important clinical factors and associated mutations.

Similarities in the Age-Specific Incidence of Colon and Testicular Cancers.

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Soto-Ortiz, Luis; Brody, James P

2013-01-01

Colon cancers are thought to be an inevitable result of aging, while testicular cancers are thought to develop in only a small fraction of men, beginning in utero. These models of carcinogenesis are, in part, based upon age-specific incidence data. The specific incidence for colon cancer appears to monotonically increase with age, while that of testicular cancer increases to a maximum value at about 35 years of age, then declines to nearly zero by the age of 80. We hypothesized that the age-specific incidence for these two cancers is similar; the apparent difference is caused by a longer development time for colon cancer and the lack of age-specific incidence data for people over 84 years of age. Here we show that a single distribution can describe the age-specific incidence of both colon carcinoma and testicular cancer. Furthermore, this distribution predicts that the specific incidence of colon cancer should reach a maximum at about age 90 and then decrease. Data on the incidence of colon carcinoma for women aged 85-99, acquired from SEER and the US Census, is consistent with this prediction. We conclude that the age specific data for testicular cancers and colon cancers is similar, suggesting that the underlying process leading to the development of these two forms of cancer may be similar.

Similarities in the Age-Specific Incidence of Colon and Testicular Cancers.

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Luis Soto-Ortiz

Full Text Available Colon cancers are thought to be an inevitable result of aging, while testicular cancers are thought to develop in only a small fraction of men, beginning in utero. These models of carcinogenesis are, in part, based upon age-specific incidence data. The specific incidence for colon cancer appears to monotonically increase with age, while that of testicular cancer increases to a maximum value at about 35 years of age, then declines to nearly zero by the age of 80. We hypothesized that the age-specific incidence for these two cancers is similar; the apparent difference is caused by a longer development time for colon cancer and the lack of age-specific incidence data for people over 84 years of age. Here we show that a single distribution can describe the age-specific incidence of both colon carcinoma and testicular cancer. Furthermore, this distribution predicts that the specific incidence of colon cancer should reach a maximum at about age 90 and then decrease. Data on the incidence of colon carcinoma for women aged 85-99, acquired from SEER and the US Census, is consistent with this prediction. We conclude that the age specific data for testicular cancers and colon cancers is similar, suggesting that the underlying process leading to the development of these two forms of cancer may be similar.

Relationship between exploitation, oscillation, MSY and extinction.

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Ghosh, Bapan; Kar, T K; Legovic, T

2014-10-01

We give answers to two important problems arising in current fisheries: (i) how maximum sustainable yield (MSY) policy is influenced by the initial population level, and (ii) how harvesting, oscillation and MSY are related to each other in prey-predator systems. To examine the impact of initial population on exploitation, we analyze a single species model with strong Allee effect. It is found that even when the MSY exists, the dynamic solution may not converge to the equilibrium stock if the initial population level is higher but near the critical threshold level. In a prey-predator system with Allee effect in the prey species, the initial population does not have such important impact neither on MSY nor on maximum sustainable total yield (MSTY). However, harvesting the top predator may cause extinction of all species if odd number of trophic levels exist in the ecosystem. With regard to the second problem, we study two prey-predator models and establish that increasing harvesting effort either on prey, predator or both prey and predator destroys previously existing oscillation. Moreover, equilibrium stock both at MSY and MSTY level is stable. We also discuss the validity of found results to other prey-predator systems. Copyright © 2014 Elsevier Inc. All rights reserved.

Overexpression of Long Non-Coding RNA TUG1 Promotes Colon Cancer Progression.

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Zhai, Hui-Yuan; Sui, Ming-Hua; Yu, Xiao; Qu, Zhen; Hu, Jin-Chen; Sun, Hai-Qing; Zheng, Hai-Tao; Zhou, Kai; Jiang, Li-Xin

2016-09-16

BACKGROUND Colon cancer is one of the most prevalent and deadly cancers worldwide. It is still necessary to further define the mechanisms and explore therapeutic targets of colon cancer. Dysregulation of long noncoding RNAs (lncRNAs) has been shown to be correlated with diverse biological processes, including tumorigenesis. This study aimed to characterize the biological mechanism of taurine-upregulated gene 1 (TUG1) in colon cancer. MATERIAL AND METHODS qRT-PCR was used to analyze the expression level of TUG1 and p63 in 75 colon cancer tissues and the matched adjacent non-tumor tissue. In vitro, cultured colon cancer cell lines HCT-116 and LoVo were used as cell models. TUG1 and p63 were silenced via transferring siRNA into HCT-116 or LoVo. The effects of TUG1 were investigated by examining cell proliferation, apoptosis, and migration. RESULTS Among the 75 colon cancer cases, the expression of TUG1 was significantly higher in colon cancer tissues compared with the matched adjacent non-tumor tissue, while p63 expression was lower in the tumor tissue. In HCT-116 and LoVo, the expression of TUG1 was significantly increased by p63 siRNA transfection. Furthermore, down-regulation of TUG1 by siRNA significantly inhibited the cell proliferation and promoted colon cancer cell apoptosis. In addition, inhibition of TUG1 expression significantly blocked the cell migration ability of colon cancer cells. CONCLUSIONS LncRNA TUG1 may serve as a potential oncogene for colon cancer. Overexpressed TUG1 may contribute to promoting cell proliferation and migration in colon cancer cells.

Combination of capecitabine and ludartin inhibits colon cancer ...

African Journals Online (AJOL)

Methods: Mice model of colon cancer was used in this study. Quantitative ... mRNA. Micro-vessel density was assessed using immunohistochemical analysis. ... increase in white blood cell (WBC) count, and increased median survival time of colon cancer mice from ..... tumor cells is associated with the development of.

Colonic macrophage polarization in homeostasis, inflammation, and cancer

Science.gov (United States)

Appleyard, Caroline B.

2016-01-01

Our review focuses on the colonic macrophage, a monocyte-derived, tissue-resident macrophage, and the role it plays in health and disease, specifically in inflammatory conditions such as inflammatory bowel disease and cancer of the colon and rectum. We give special emphasis to macrophage polarization, or phenotype, in these different states. We focus on macrophages because they are one of the most numerous leukocytes in the colon, and because they normally contribute to homeostasis through an anti-inflammatory phenotype. However, in conditions such as inflammatory bowel disease, proinflammatory macrophages are increased in the colon and have been linked to disease severity and progression. In colorectal cancer, tumor cells may employ anti-inflammatory macrophages to promote tumor growth and dissemination, whereas proinflammatory macrophages may antagonize tumor growth. Given the key roles that this cell type plays in homeostasis, inflammation, and cancer, the colonic macrophage is an intriguing therapeutic target. As such, potential macrophage-targeting strategies are discussed. PMID:27229123

Early colon cancer : findings on double contrast barium enema

International Nuclear Information System (INIS)

Kim, Seung Kwon; Lim, Jae Hoon; Lee, Soon Jin; Lim, Hyo Keun

1998-01-01

The purpose of this study is to describe the radiologic findings of early colon cancer on double-contrast barium enema. We retrospectively reviewed the double-contrast barium enemas of eight patients (M:F = 6:2; mean age : 67 yrs; range : 48-77 yrs) who were pathologically proven to be early colon cancer. The location, size and gross morphology of lesions was evaluated using double-contrast barium enema, while depth of invasion, degree of differentiation, precancerous lesions and lymph node metastasis were evaluated histopathologically. Early colon cancer was found in the rectum (n=4), sigmoid colon (n=3) and ascending colon (n=1). The size of mass ranged from 2.3 ∼ 8.3 (mean, 4.6) cm. And the polypoid type was most common (n=7); this was subdivided into sessile (Is, n=5), semipedunculated (Isp, n=1) and pedunculated type (Ip, n=1). Another mass was a sessile polypoid combined with a flat depressed lesion. In eight cases, four cancers were confined to the mucosa, while the remaining four had infiltrated the submucosa. Most cancers arose from villous and villotubular adenoma. All cases were well-differentiated adenocarcinoma and no metastasis to lymph nodes had occurred. In early colon cancer, lesions were mainly polypoid and large. Most arose from villous and villotubular adenoma. (author). 19 refs., 1 tab., 3 figs

Identification of colonic fibroblast secretomes reveals secretory factors regulating colon cancer cell proliferation.

Science.gov (United States)

Chen, Sun-Xia; Xu, Xiao-En; Wang, Xiao-Qing; Cui, Shu-Jian; Xu, Lei-Lei; Jiang, Ying-Hua; Zhang, Yang; Yan, Hai-Bo; Zhang, Qian; Qiao, Jie; Yang, Peng-Yuan; Liu, Feng

2014-10-14

Stromal microenvironment influences tumor cell proliferation and migration. Fibroblasts represent the most abundant stromal constituents. Here, we established two pairs of normal fibroblast (NF) and cancer-associated fibroblast (CAF) cultures from colorectal adenocarcinoma tissues and the normal counterparts. The NFs and CAFs were stained positive for typical fibroblast markers and inhibited colon cancer (CC) cell proliferation in in vitro cocultures and in xenograft mouse models. The fibroblast conditioned media were analyzed using LC-MS and 227 proteins were identified at a false discovery rate of 1.3%, including 131 putative secretory and 20 plasma membrane proteins. These proteins were enriched for functional categories of extracellular matrix, adhesion, cell motion, inflammatory response, redox homeostasis and peptidase inhibitor. Secreted protein acidic and rich in cysteine, transgelin, follistatin-related protein 1 (FSTL1) and decorin was abundant in the fibroblast secretome as confirmed by Western blot. Silencing of FSTL1 and transgelin in colonic fibroblast cell line CCD-18Co induced an accelerated proliferation of CC cells in cocultures. Exogenous FSTL1 attenuates CC cell proliferation in a negative fashion. FSTL1 was upregulated in CC patient plasma and cancerous tissues but had no implication in prognosis. Our results provided novel insights into the molecular signatures and modulatory role of CC associated fibroblasts. In this study, a label-free LC-MS was performed to analyze the secretomes of two paired primary fibroblasts, which were isolated from fresh surgical specimen of colorectal adenocarcinoma and adjacent normal colonic tissues and exhibited negative modulatory activity for colon cancer cell growth in in vitro cocultures and in vivo xenograph mouse models. Follistatin-related protein 1 was further revealed to be one of the stroma-derived factors of potential suppression role for colon cancer cell proliferation. Our results provide novel

Clinical Significance and Prognostic Relevance of Microsatellite Instability in Sporadic Colorectal Cancer Patients

Directory of Open Access Journals (Sweden)

Angelika Copija

2017-01-01

Full Text Available Microsatellite instability (MSI is a marker of the replication error phenotype. It is caused by impaired DNA mismatch repair processes (MMR, resulting in ineffectiveness of the mechanisms responsible for the DNA replication precision and postreplicative DNA repair. MSI underlies the pathogenesis of 10%–20% of colorectal cancer (CRC cases. The data about the potential value of MMR status as a predictive factor for 5-fluorouracil (FU-based chemotherapy remain unclear. According to National Comprehensive Cancer Network updated guidelines, MSI testing is recommended for all patients with stage II CRC because patients with MSI-H (high-frequency MSI tumour may have a good prognosis and obtain no benefit from 5-FU-based adjuvant chemotherapy. The significance of the MSI status as a predictive factor for patients with metastatic disease was not confirmed. The association between the MSI status and the efficacy of the therapy based on anti-programmed death-1 receptor inhibitors requires further studies.

Screening for colorectal cancer in defunctioned colons.

Science.gov (United States)

Akbar, Fayyaz; Quyn, Aaron; Steele, Robert

2018-01-01

Objectives Population-based colorectal (bowel) cancer screening using faecal occult blood tests leads to a reduction in cause-specific mortality. However, in people where the colon is defunctioned, the use of standard faecal occult blood test is not appropriate. The aim of this study was to examine the current trends of clinical practice for colorectal cancer screening in people with defunctioned colons. Methods An online survey was performed using SurveyMonkey. All members of the Association of Coloproctology of Great Britain and Ireland were invited by email to participate. Reminders were sent to non-responders and partial responders till six weeks. All responses were included in our analysis. Results Of the 206 (34.59%) questionnaires completed, all questions were answered in 110 (55.8%). Among responders, 94 (85.4%) were colorectal consultant surgeons, 72% had worked in their current capacity for more than five years, and 105 (50.9%) had encountered colorectal cancer in defunctioned colons during their career. Some 72.2% of responders stated that a screening test for colorectal cancer in patients with defunctioned colons was currently not offered, or that they did not know whether or not it was offered in their area. Conclusions Bowel screening in the United Kingdom is currently not offered to 72.2% of the age appropriate population with defunctioned colons. Among responding colorectal surgeons, 50% had encountered colorectal cancer in such patients. There is considerable variability in clinical practice regarding the optimal age for onset of screening, time interval, and the optimal modality to offer for screening in such cases.

Microchimerism and survival after breast and colon cancer diagnosis

DEFF Research Database (Denmark)

Kamper-Jørgensen, Mads

2012-01-01

Recently, we reported microchimerism to be oppositely associated with maternal breast and colon cancer. In women with a blood test positive for male microchimerism the risk of breast cancer development was reduced to one third, whereas the risk of colon cancer was elevated 4-fold. In this article...

Microsatellite instability in colorectal cancer and association with thymidylate synthase and dihydropyrimidine dehydrogenase expression

DEFF Research Database (Denmark)

Jensen, Søren A; Vainer, Ben; Kruhøffer, Mogens

2009-01-01

unclarified. The association of MSI and MMR status with outcome and with thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) expression in colorectal cancer were evaluated. METHODS: MSI in five reference loci, MMR enzymes (hMSH2, hMSH6, hMLH1 and hPMS2), thymidylate synthase (TS....... Absence of repair protein expression was assessed in 52 (17.0%) tumors, which had primarily lost hMLH1 in 39 (12.7%), hMSH2 in 5 (1.6%), and hMSH6 in 8 (2.6%) tumors. In multivariate analysis MSI (instable) compared to MSS (stable) tumors were significantly associated with lower risk of recurrence (hazard...

A Prospective Evaluation of Plasma Polyphenol Levels and Colon Cancer Risk

DEFF Research Database (Denmark)

Murphy, Neil; Achaintre, David; Zamora-Ros, Raul

2018-01-01

Polyphenols have been shown to exert biological activity in experimental models of colon cancer; however, human data linking specific polyphenols to colon cancer is limited. We assessed the relationship between pre-diagnostic plasma polyphenols and colon cancer risk in a case-control study nested...

Immunohistochemical study of p53 overexpression in radiation-induced colon cancers

International Nuclear Information System (INIS)

Minami, Kazunori; Hayashi, Nobuyuki; Mokarim, A.; Matsuzaki, Sumihiro; Ito, Masahiro; Sekine, Ichiro.

1998-01-01

The expressions of p53 and proliferating cell nuclear antigen (PCNA) were studied immunohistochemically from paraffin sections of 7 cases (9 lesions) of radiation-induced colon cancer and 42 cases of spontaneous colon cancer. Age distribution of radiation-induced and spontaneous colon cancer were 68.1 years (range, 56 to 77 years) and 67.4 years (range, 31 to 85 years), respectively. Among the radiation-induced colon cancers, there were 3 lesions of mucinous carcinoma (33%), a much higher than found for spontaneous mucinous cancer. Immunohistochemically, p53 protein expression was detected in 7/9 (78%) of radiation-induced cancers and in 23/42 (55%) of spontaneous colon cancers. χ 2 analysis found no significant differences between radiation-induced and spontaneous colon cancers in age distribution or p53-positive staining for frequency, histopathology, or Dukes'' classification. In radiation colitis around the cancers including aberrant crypts, spotted p53 staining and abnormal and scattered PCNA-positive staining were observed. In histologically normal cells, p53 staining was almost absent and PCNA-positive staining was regularly observed in the lower half of the crypt. In radiation colitis including aberrant glands, cellular proliferation increased and spotted p53 expression was observed. This study suggests that radiation colitis and aberrant glands might possess malignant potential and deeply associate with carcinogenesis of radiation-induced colon cancer. (author)

MLH1-rheMac hereditary nonpolyposis colorectal cancer syndrome in rhesus macaques.

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Brammer, David W; Gillespie, Patrick J; Tian, Mei; Young, Daniel; Raveendran, Muthuswamy; Williams, Lawrence E; Gagea, Mihai; Benavides, Fernando J; Perez, Carlos J; Broaddus, Russell R; Bernacky, Bruce J; Barnhart, Kirstin F; Alauddin, Mian M; Bhutani, Manoop S; Gibbs, Richard A; Sidman, Richard L; Pasqualini, Renata; Arap, Wadih; Rogers, Jeffrey; Abee, Christian R; Gelovani, Juri G

2018-03-13

Over the past two decades, 33 cases of colonic adenocarcinomas have been diagnosed in rhesus macaques ( Macaca mulatta ) at the nonhuman primate colony of the Keeling Center for Comparative Medicine and Research at The University of Texas MD Anderson Cancer Center. The distinctive feature in these cases, based on PET/computed tomography (CT) imaging, was the presence of two or three tumor lesions in different locations, including proximal to the ileocecal juncture, proximal to the hepatic flexure, and/or in the sigmoid colon. These colon carcinoma lesions selectively accumulated [ 18 F]fluorodeoxyglucose ([ 18 F]FDG) and [ 18 F]fluoroacetate ([ 18 F]FACE) at high levels, reflecting elevated carbohydrate and fatty acid metabolism in these tumors. In contrast, the accumulation of [ 18 F]fluorothymidine ([ 18 F]FLT) was less significant, reflecting slow proliferative activity in these tumors. The diagnoses of colon carcinomas were confirmed by endoscopy. The expression of MLH1, MSH2, and MSH6 proteins and the degree of microsatellite instability (MSI) was assessed in colon carcinomas. The loss of MLH1 protein expression was observed in all tumors and was associated with a deletion mutation in the MLH1 promoter region and/or multiple single-nucleotide polymorphism (SNP) mutations in the MLH1 gene. All tumors exhibited various degrees of MSI. The pedigree analysis of this rhesus macaque population revealed several clusters of affected animals related to each other over several generations, suggesting an autosomal dominant transmission of susceptibility for colon cancer. The newly discovered hereditary nonpolyposis colorectal cancer syndrome in rhesus macaques, termed MLH1 -rheMac, may serve as a model for development of novel approaches to diagnosis and therapy of Lynch syndrome in humans. Copyright © 2018 the Author(s). Published by PNAS.

Lynch syndrome and Lynch syndrome mimics: The growing complex landscape of hereditary colon cancer

Science.gov (United States)

Carethers, John M; Stoffel, Elena M

2015-01-01

Hereditary non-polyposis colorectal cancer (HNPCC) was previously synonymous with Lynch syndrome; however, identification of the role of germline mutations in the DNA mismatch repair (MMR) genes has made it possible to differentiate Lynch syndrome from other conditions associated with familial colorectal cancer (CRC). Broadly, HNPCC may be dichotomized into conditions that demonstrate defective DNA MMR and microsatellite instability (MSI) vs those conditions that demonstrate intact DNA MMR. Conditions characterized by MMR deficient CRCs include Lynch syndrome (germline MMR mutation), Lynch-like syndrome (biallelic somatic MMR mutations), constitutional MMR deficiency syndrome (biallelic germline MMR mutations), and sporadic MSI CRC (somatic biallelic methylation of MLH1). HNPCC conditions with intact DNA MMR associated with familial CRC include polymerase proofreading associated polyposis and familial colorectal cancer type X. Although next generation sequencing technologies have elucidated the genetic cause for some HNPCC conditions, others remain genetically undefined. Differentiating between Lynch syndrome and the other HNPCC disorders has profound implications for cancer risk assessment and surveillance of affected patients and their at-risk relatives. Clinical suspicion coupled with molecular tumor analysis and testing for germline mutations can help differentiate the clinical mimicry within HNPCC and facilitate diagnosis and management. PMID:26309352

Lynch syndrome and Lynch syndrome mimics: The growing complex landscape of hereditary colon cancer.

Science.gov (United States)

Carethers, John M; Stoffel, Elena M

2015-08-21

Hereditary non-polyposis colorectal cancer (HNPCC) was previously synonymous with Lynch syndrome; however, identification of the role of germline mutations in the DNA mismatch repair (MMR) genes has made it possible to differentiate Lynch syndrome from other conditions associated with familial colorectal cancer (CRC). Broadly, HNPCC may be dichotomized into conditions that demonstrate defective DNA MMR and microsatellite instability (MSI) vs those conditions that demonstrate intact DNA MMR. Conditions characterized by MMR deficient CRCs include Lynch syndrome (germline MMR mutation), Lynch-like syndrome (biallelic somatic MMR mutations), constitutional MMR deficiency syndrome (biallelic germline MMR mutations), and sporadic MSI CRC (somatic biallelic methylation of MLH1). HNPCC conditions with intact DNA MMR associated with familial CRC include polymerase proofreading associated polyposis and familial colorectal cancer type X. Although next generation sequencing technologies have elucidated the genetic cause for some HNPCC conditions, others remain genetically undefined. Differentiating between Lynch syndrome and the other HNPCC disorders has profound implications for cancer risk assessment and surveillance of affected patients and their at-risk relatives. Clinical suspicion coupled with molecular tumor analysis and testing for germline mutations can help differentiate the clinical mimicry within HNPCC and facilitate diagnosis and management.

Nutraceuticals as potential therapeutic agents for colon cancer: a review

OpenAIRE

Kuppusamy, Palaniselvam; Yusoff, Mashitah M.; Maniam, Gaanty Pragas; Ichwan, Solachuddin Jauhari Arief; Soundharrajan, Ilavenil; Govindan, Natanamurugaraj

2014-01-01

Colon cancer is a world-wide health problem and the second-most dangerous type of cancer, affecting both men and women. The modern diet and lifestyles, with high meat consumption and excessive alcohol use, along with limited physical activity has led to an increasing mortality rate for colon cancer worldwide. As a result, there is a need to develop novel and environmentally benign drug therapies for colon cancer. Currently, nutraceuticals play an increasingly important role in the treatment o...

Colon Cancer Risk Assessment - Gauss Program

Science.gov (United States)

An executable file (in GAUSS) that projects absolute colon cancer risk (with confidence intervals) according to NCI’s Colorectal Cancer Risk Assessment Tool (CCRAT) algorithm. GAUSS is not needed to run the program.

Use of capecitabine in management of early colon cancer

Directory of Open Access Journals (Sweden)

Cassidy J

2011-08-01

Full Text Available H Hameed, J CassidyBeatson West of Scotland Cancer Centre, Glasgow, Scotland, UKAbstract: Capecitabine (Xeloda®, Roche, Basel, Switzerland is a pro-drug of 5-fluorouracil (5-FU, and it is converted to 5-FU in the cancer cell by enzymatic degradation. The role of capecitabine in colorectal cancer has evolved in the last 15 years. In early trials in the metastatic setting, capecitabine has shown superior response rates compared with those achieved with 5-FU (Mayo Clinic regimen (26% vs 17%, with equivalent progression-free survival and overall survival. In the adjuvant setting, the Xeloda in Adjuvant Colon Cancer Therapy (X-ACT trial demonstrated that capecitabine as a single agent led to improvement in relapse-free survival (hazard ratio: 0.86, 95% confidence interval: 0.74–0.99, P = 0.04 and was associated with significantly fewer adverse events than 5-FU plus leucovorin (LV, folinic acid. On the basis of the X-ACT trial, capecitabine was approved by the United States Food and Drug Administration, the National Institute for Clinical Excellence, and the Scottish Medicines Consortium as monotherapy for the adjuvant treatment of stage III colon cancer. The next step was to incorporate capecitabine into combination therapy. The XELOXA trial studied the combination of capecitabine and oxaliplatin (XELOX vs 5-FU/LV and demonstrated 5-year disease-free survival of 66% for XELOX, compared with 60% for 5-FU/LV. The toxicity profile was also quite comparable in the two arms. So both the single agent use of capecitabine as well as in combination with oxaliplatin can be considered as part of the standard of care in management of early colon cancer in appropriately selected patient groups.Keywords: 5-fluorouracil, 5-FU, leucovorin, folinic acid, LV, XELOX, oxaliplatin, FOLFOX

Combination of capecitabine and ludartin inhibits colon cancer ...

African Journals Online (AJOL)

Purpose: To investigate the efficacy of capecitabine and ludartin in the treatment of colon cancer in mice. Methods: Mice model of colon cancer was used in this study. Quantitative real-time polymerase chain reaction (Qrt-PCR) was used to quantify the expression of vascular endothelial growth factor (VEGF) mRNA.

A Colon Targeted Delivery System for Resveratrol Enriching in pH Responsive-Model

Directory of Open Access Journals (Sweden)

Hashem Andishmand, Hamed Hamishehkar, Afshin Babazadeh, Arezou Taghvimi, Mohammad Amin Mohammadifar, Mahnaz Tabibiazar

2017-03-01

Full Text Available Background: Resveratrol effects on the prevention and treatment of colon cancer have been well documented recently, but low solubility, rapid absorption and metabolism of resveratrol limit its beneficial effects on colon cancer. Designing a formulation that enhances the solubility of resveratrol, protects resveratrol from oxidation and isomerization, and delivers it to the colon is a priority of food and drug industry. In this study, resveratrol-polyethylene glycol (PEG-loaded pectin-chitosan polyelectrolyte complex was designed as a colon targeted delivery system. Methods: The effects of adding PEG, ultra-sonication time, pH, and pectin to chitosan ratio were investigated on particle size, polydispersity index (PDI, zeta potential by particle size analyzer, and scanning electron microscopy (SEM. Encapsulation efficiency (EE, release of resveratrol in simulated gastrointestinal fluid, and different pHs were analyzed via High Performance Liquid Chromatography (HPLC. Antioxidant activity was measured by (2, 2-diphenyl-1-picryl-hydrazyl-hydrate DPPH free-radical method. Results: Results showed that colloidal stable micro-particles (725 ± 20 nm with PDI < 0.3 and zeta potential +27 ± 2 mV was formed in the ratio of 5:1 of pectin to chitosan w/v % after a 10-min sonication. Encapsulation efficiency was 81 ± 7 %. The reduction of antioxidant activity of resveratrol loaded micro-particles after one month was less than 13%. Micro-particles released about 33% of resveratrol in the simulated gastric and intestinal fluids. Conclusion: Two-thirds of the loaded resveratrol in Pectin-Chitosan complex reached colon. The developed system had enough specification for enriching fruit based drinks due to remarkable colloidal stability in the pH range of 3.5 to 4.5.

Clinicopathologic factors identify sporadic mismatch repair-defective colon cancers

DEFF Research Database (Denmark)

Halvarsson, Britta; Anderson, Harald; Domanska, Katarina

2008-01-01

Identification of sporadic mismatch repair (MMR)-defective colon cancers is increasingly demanded for decisions on adjuvant therapies. We evaluated clinicopathologic factors for the identification of these prognostically favorable tumors. Histopathologic features in 238 consecutive colon cancers...

Systemic chemotherapy induces microsatellite instability in the peripheral blood mononuclear cells of breast cancer patients

International Nuclear Information System (INIS)

Fonseca, Fernando LA; Sant Ana, Aleksandra VL; Bendit, Israel; Arias, Vitor; Costa, Luciano J; Pinhal, Aparecida A; Giglio, Auro del

2005-01-01

Systemic chemotherapy is an important part of treatment for breast cancer. We conducted the present study to evaluate whether systemic chemotherapy could produce microsatellite instability (MSI) in the peripheral blood mononuclear cell fraction of breast cancer patients. We studied 119 sequential blood samples from 30 previously untreated breast cancer patients before, during and after chemotherapy. For comparison, we also evaluated 20 women who had no relevant medical history (control group). In 27 out of 30 patients we observed MSI in at least one sample, and six patients had loss of heterozygosity. We found a significant correlation between the number of MSI events per sample and chemotherapy with alkylating agents (P < 0.0001). We also observed an inverse correlation between the percentage of cells positive for hMSH2 and the number of MSI events per sample (P = 0.00019) and use of alkylating agents (P = 0.019). We conclude that systemic chemotherapy may induce MSI and loss of heterozygosity in peripheral blood mononuclear cells from breast cancer patients receiving alkylating agents, possibly mediated by a chemotherapy-induced decrease in the expression of hMSH2. These effects may be related to the generation of secondary leukaemia in some patients, and may also intensify the genetic instability of tumours and increase resistance to treatment

Red meat and colon cancer : a possible role for heme

NARCIS (Netherlands)

Sesink, Aloysius Lambertus Antonia

2000-01-01

Sporadic colon cancer is a multifactorial aging disease affected by long-term exposure to environmental risk factors. Epidemiological studies have shown that risk for colon cancer is associated with diets high in red meat and/or animal fat. The mechanisms by which colonic tumors arise are, however,

Fruits, vegetables and hMLH1 protein-deficient and-proficient colon cancer: the Netherlands Cohort Study

NARCIS (Netherlands)

Wark, P.A.; Weijenberg, M.P.; Veer, van 't P.; Wijhe, van G.; Luchtenborg, M.; Muijen, van G.N.P.; Goeij, de A.F.P.M.; Goldbohm, R.A.; Brandt, van den P.A.

2005-01-01

Clinical and pathologic differences exist between colon carcinomas deficient and proficient in the mismatch repair protein hMLH1. Animal and in vitro studies suggest that fruits, vegetables, folate, and antioxidants are associated with colonic expression of mismatch repair genes.METHODS:

Vaccine Therapy in Treating Patients With Colon, Pancreatic, or Lung Cancer

Science.gov (United States)

2015-04-27

Recurrent Colon Cancer; Extensive Stage Small Cell Lung Cancer; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Limited Stage Small Cell Lung Cancer; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Stage III Non-small Cell Lung Cancer; Stage I Pancreatic Cancer; Stage II Non-small Cell Lung Cancer; Stage IVB Pancreatic Cancer; Stage II Pancreatic Cancer; Stage III Colon Cancer; Stage IVA Pancreatic Cancer

Surgical and pathological outcomes of laparoscopic surgery for transverse colon cancer.

Science.gov (United States)

Lee, Y S; Lee, I K; Kang, W K; Cho, H M; Park, J K; Oh, S T; Kim, J G; Kim, Y H

2008-07-01

Several multi-institutional prospective randomized trials have demonstrated short-term benefits using laparoscopy. Now the laparoscopic approach is accepted as an alternative to open surgery for colon cancer. However, in prior trials, the transverse colon was excluded. Therefore, it has not been determined whether laparoscopy can be used in the setting of transverse colon cancer. This study evaluated the peri-operative clinical outcomes and oncological quality by pathologic outcomes of laparoscopic surgery for transverse colon cancer. Analysis of the medical records of patients who underwent laparoscopic colorectal resection from August 2004 to November 2007 was made. Computed tomography, barium enema, and colonoscopy were performed to localize the tumor preoperatively. Extended right hemicolectomy, transverse colectomy, and extended left hemicolectomy were performed for transverse colon cancer. Surgical outcomes and pathologic outcomes were compared between transverse colon cancer (TCC) and other site colon cancer (OSCC). Of the 312 colorectal cancer patients, 94 patients underwent laparoscopic surgery for OSCC, and 34 patients underwent laparoscopic surgery for TCC. Patients with TCC were similar to patients with OSCC in age, gender, body mass index, operating time, blood loss, time to pass flatus, start of diet, hospital stay, tumor size, distal resection margin, proximal resection margin, number of lymph nodes, and radial margin. One case in TCC and three cases in OSCC were converted to open surgery. Laparoscopic surgery for transverse colon cancer and OSCC had similar peri-operative clinical and acceptable pathological outcomes.

Prognostic value of microscopic peritoneal dissemination: comparison between colon and gastric cancer.

Science.gov (United States)

Vogel, P; Rüschoff, J; Kümmel, S; Zirngibl, H; Hofstädter, F; Hohenberger, W; Jauch, K W

2000-01-01

We evaluated the incidence and prognostic relevance of microscopic intraperitoneal tumor cell dissemination of colon cancer in comparison with dissemination of gastric cancer as a rational for additive intraperitoneal therapy. Peritoneal washouts of 90 patients with colon and 111 patients with gastric cancer were investigated prospectively. Sixty patients with benign diseases and 8 patients with histologically proven gross visible peritoneal carcinomatosis served as controls. Intraoperatively, 100 ml of warm NaCl 0.9 percent were instilled and 20 ml were reaspirated. In all patients hematoxylin and eosin staining (conventional cytology) was performed. Additionally, in 36 patients with colon cancer and 47 patients with gastric cancer, immunostaining with the HEA-125 antibody (immunocytology) was prepared. The results of cytology were assessed for an association with TNM category and cancer grade, based on all patients, and with patient survival, among the R0 resected patients. In conventional cytology 35.5 percent (32/90) of patients with colon cancer and 42.3 percent (47/111) of patients with gastric cancer had a positive cytology. In immunocytology 47.2 percent (17/36) of patients with colon cancer and 46.8 percent (22/47) of patients with gastric cancer were positive. In colon cancer, positive conventional cytology was associated with pT and M category (P = 0.044 and P = 0.0002), whereas immunocytology was only associated with M category (P = 0.007). No association was found between nodal status and immunocytology in colon cancer and with the grading. There was a statistically significant correlation between pT M category and conventional and immunocytology in gastric cancer (P influences survival time after R0 resections only in patients with gastric but not with colon cancer, our results may provide a basis for a decision on additive, prophylactic (intraperitoneal) therapy in gastric but not colon cancer.

Sigmoid colon cancer arising in a diverticulum of the colon with involvement of the urinary bladder: a case report and review of the literature.

Science.gov (United States)

Yagi, Yasumichi; Shoji, Yasuhiro; Sasaki, Shozo; Yoshikawa, Akemi; Tsukioka, Yuji; Fukushima, Wataru; Hirosawa, Hisashi; Izumi, Ryohei; Saito, Katsuhiko

2014-05-13

Colon cancer can arise from the mucosa in a colonic diverticulum. Although colon diverticulum is a common disease, few cases have been previously reported on colon cancer associated with a diverticulum. We report a rare case of sigmoid colon cancer arising in a diverticulum with involvement of the urinary bladder, which presented characteristic radiographic images. A 73-year-old man was admitted to our hospital for macroscopic hematuria. Computed tomography and magnetic resonance imaging revealed a sigmoid colon tumor that protruded into the urinary bladder lumen. The radiographs showed a tumor with a characteristic dumbbell-shaped appearance. Colonoscopy showed a type 1 cancer and multiple diverticula in the sigmoid colon. A diagnosis of sigmoid colon cancer with involvement of the urinary bladder was made based on the pathological findings of the biopsied specimens. We performed sigmoidectomy and total resection of the urinary bladder with colostomy and urinary tract diversion. Histopathological findings showed the presence of a colovesical fistula due to extramurally growing colon cancer. Around the colon cancer, the normal colon mucosa was depressed sharply with lack of the muscular layer, suggesting that the colon cancer was arising from a colon diverticulum. The present case is the first report of sigmoid colon cancer arising in a diverticulum with involvement of the urinary bladder. Due to an accurate preoperative radiological diagnosis, we were able to successfully perform a curative resection for sigmoid colon cancer arising in a diverticulum with involvement of the urinary bladder.

Role of pomegranate and citrus fruit juices in colon cancer prevention

Science.gov (United States)

Jaganathan, Saravana Kumar; Vellayappan, Muthu Vignesh; Narasimhan, Gayathri; Supriyanto, Eko

2014-01-01

Colorectal cancer is the second leading cause of cancer-related deaths in the United States. Recent studies prove that though chemotherapeutic agents are being used for the treatment of colon cancer, they become non-effective when the cancer progresses to an invasive stage. Since consumption of certain dietary agents has been linked with various cancers, fruit juices have been investigated for their consistently protective effect against colon cancer. The unique biochemical composition of fruit juices is responsible for their anticancer properties. In this review, the chemo-preventive effect of fruit juices such as pomegranate and citrus juices against colon cancer are discussed. For this purpose, the bioavailability, in vitro and in vivo effects of these fruit juices on colorectal cancer are highlighted. Moreover, there is a scarcity of studies involving human trials to estimate the preventive nature of these juices against colon cancer. This review will support the need for more preclinical tests with these crude juices and their constituents in different colorectal cancer cell lines and also some epidemiological studies in order to have a better understanding and promote pomegranate and citrus juices as crusaders against colon cancer. PMID:24782614

Identification of downstream metastasis-associated target genes regulated by LSD1 in colon cancer cells.

Science.gov (United States)

Chen, Jiang; Ding, Jie; Wang, Ziwei; Zhu, Jian; Wang, Xuejian; Du, Jiyi

2017-03-21

This study aims to identify downstream target genes regulated by lysine-specific demethylase 1 (LSD1) in colon cancer cells and investigate the molecular mechanisms of LSD1 influencing invasion and metastasis of colon cancer. We obtained the expression changes of downstream target genes regulated by small-interfering RNA-LSD1 and LSD1-overexpression via gene expression profiling in two human colon cancer cell lines. An Affymetrix Human Transcriptome Array 2.0 was used to identify differentially expressed genes (DEGs). We screened out LSD1-target gene associated with proliferation, metastasis, and invasion from DEGs via Gene Ontology and Pathway Studio. Subsequently, four key genes (CABYR, FOXF2, TLE4, and CDH1) were computationally predicted as metastasis-related LSD1-target genes. ChIp-PCR was applied after RT-PCR and Western blot validations to detect the occupancy of LSD1-target gene promoter-bound LSD1. A total of 3633 DEGs were significantly upregulated, and 4642 DEGs were downregulated in LSD1-silenced SW620 cells. A total of 4047 DEGs and 4240 DEGs were upregulated and downregulated in LSD1-overexpressed HT-29 cells, respectively. RT-PCR and Western blot validated the microarray analysis results. ChIP assay results demonstrated that LSD1 might be negative regulators for target genes CABYR and CDH1. The expression level of LSD1 is negatively correlated with mono- and dimethylation of histone H3 lysine4(H3K4) at LSD1- target gene promoter region. No significant mono-methylation and dimethylation of H3 lysine9 methylation was detected at the promoter region of CABYR and CDH1. LSD1- depletion contributed to the upregulation of CABYR and CDH1 through enhancing the dimethylation of H3K4 at the LSD1-target genes promoter. LSD1- overexpression mediated the downregulation of CABYR and CDH1expression through decreasing the mono- and dimethylation of H3K4 at LSD1-target gene promoter in colon cancer cells. CABYR and CDH1 might be potential LSD1-target genes in colon

Predictive utility of cyclo-oxygenase-2 expression by colon and rectal cancer.

Science.gov (United States)

Lobo Prabhu, Kristel C; Vu, Lan; Chan, Simon K; Phang, Terry; Gown, Allen; Jones, Steven J; Wiseman, Sam M

2014-05-01

Cyclo-oxygenase-2 (COX-2), an inducible enzyme expressed in areas of inflammation, is a target of interest for colorectal cancer therapy. Currently, the predictive significance of COX-2 in colorectal cancer remains unclear. Tissue microarrays were constructed using 118 colon cancer and 85 rectal cancer specimens; 44 synchronous metastatic colon cancer and 22 rectal cancer lymph nodes were also evaluated. COX-2 expression was assessed by immunohistochemistry. Univariate analysis was used to determine the predictive significance of clinicopathologic variables. Overall survival, disease-specific survival, and disease-free survival were the main outcomes examined. COX-2 was found to be expressed in 93% of colon cancers and 87% of rectal cancers. Decreased COX-2 expression was related to decreased disease-specific survival (P = .016) and decreased disease-free survival (P = .019) in the rectal cancer cohort but not in the colon cancer cohort. COX-2 expression has predictive utility for management of rectal but not colon cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

Pitfalls in diagnosing colon cancer on abdominal CT.

Science.gov (United States)

Klang, E; Eifer, M; Kopylov, U; Belsky, V; Raskin, S; Konen, E; Amitai, M M

2017-10-01

To assess the frequency of undetected colon cancer on conventional abdominal CT and to evaluate the imaging features that are characteristic of those cancers. The present study included consecutive patients diagnosed with colorectal cancer at colonoscopy (2006-2015) who also underwent abdominal computed tomography (CT) performed for various reasons within a year prior to the colonoscopy. The frequency of undetected lesions was evaluated for the original CT interpretations ("original readers"). Two radiologists ("study readers"), blinded to the tumour location, independently performed interpretations oriented for colon cancer detection. The study readers analysed the imaging features of detected tumours (tumour shape, length, maximal wall thickness, free fluid, fat stranding, vascular engorgement, stenosis, and lymphadenopathy). Imaging features of the cancers undetected by the original readers were evaluated. The study included 127 patients. The original readers' frequency of undetected cancer was 25/127 (19.7%). Each study reader could not identify the cancer in 8/127 (6.3%) patients. Imaging features associated with undetected cancers by the original readers included the absence of fat stranding (p=0.007, p=0.003), absence of vascular engorgement (pColon cancer is undetected in 20% of abdominal CT examinations in patients subsequently proven to have colon cancer at colonoscopy. The absence of fat stranding, vascular engorgement, or lymphadenopathy, and an average tumour length of 3.3 cm are contributing factors for failure of detection. Radiologists' training should emphasis these findings as it may improve cancer detection, and clinicians should be aware of the limitations of abdominal CT. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Near-infrared Mueller matrix imaging for colonic cancer detection

Science.gov (United States)

Wang, Jianfeng; Zheng, Wei; Lin, Kan; Huang, Zhiwei

2016-03-01

Mueller matrix imaging along with polar decomposition method was employed for the colonic cancer detection by polarized light in the near-infrared spectral range (700-1100 nm). A high-speed (colonic tissues (i.e., normal and caner) were acquired. Polar decomposition was further implemented on the 16 images to derive the diattentuation, depolarization, and the retardance images. The decomposed images showed clear margin between the normal and cancerous colon tissue samples. The work shows the potential of near-infrared Mueller matrix imaging for the early diagnosis and detection of malignant lesions in the colon.

File list: Unc.Dig.20.AllAg.Colon_cancer [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Unc.Dig.20.AllAg.Colon_cancer hg19 Unclassified Digestive tract Colon cancer SRX115...0169,SRX1150170,SRX124703 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Dig.20.AllAg.Colon_cancer.bed ...

File list: Unc.Dig.50.AllAg.Colon_cancer [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Unc.Dig.50.AllAg.Colon_cancer hg19 Unclassified Digestive tract Colon cancer SRX115...0169,SRX1150170,SRX124703 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Dig.50.AllAg.Colon_cancer.bed ...

File list: Unc.Dig.10.AllAg.Colon_cancer [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Unc.Dig.10.AllAg.Colon_cancer hg19 Unclassified Digestive tract Colon cancer SRX115...0169,SRX124703,SRX1150170 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Dig.10.AllAg.Colon_cancer.bed ...

File list: Unc.Dig.05.AllAg.Colon_cancer [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Unc.Dig.05.AllAg.Colon_cancer hg19 Unclassified Digestive tract Colon cancer SRX115...0169,SRX1150170,SRX124703 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Dig.05.AllAg.Colon_cancer.bed ...

Expression and clinical significance of tyrosine phosphatase SHP-2 in colon cancer.

Science.gov (United States)

Cai, Peifen; Guo, Wenjie; Yuan, Huaqin; Li, Qian; Wang, Weicheng; Sun, Yang; Li, Xiaomin; Gu, Yanhong

2014-04-01

Protein-tyrosine phosphatase SHP-2, encoded by gene PTPN11, has been identified as a tumor-promoting factor in several types of leukemia and is hyper-activated by other mechanisms in some solid tumors including gastric cancer, breast cancer, non-small cell lung cancer (NSCLC), etc. But few were reported on the expression and significances of SHP-2 in colon cancer. Here, we detect SHP-2 expression in colon cancer cells, colon cancer-induced by AOM+DSS in mice and 232 human colon cancer specimens, including 58 groups of self-matched adjacent peritumor tissues and normal tissues. We found that compared to the normal colon tissues, SHP-2 significantly decreased in tumor tissues (Pcolon tumor cells as well as mice colon tumors. And in humans samples, low SHP-2 expression showed a significantly correlation with poor tumor differentiation (P<0.05), late TNM stage (P=0.1666) and lymph node metastasis (P<0.05). Copyright © 2013 Elsevier Masson SAS. All rights reserved.

[A case of transverse colon cancer mimicking urachal cancer].

Science.gov (United States)

Nishimura, Taku; Inoue, Ryo; Kondo, Junya; Nagashima, Yukiko; Okada, Toshimasa; Nakamura, Mitsuo; Sakata, Koichiro; Yamaguchi, Shiro; Setoguchi, Mihoko

2013-11-01

A 55-year-old man was admitted to our hospital because of abdominal distension. Computed tomography revealed an abscess in the anterior abdominal wall and invasion of the large intestine. Biopsy of the large intestine revealed adenocarcinoma. Immunohistochemically, the antigen expression profile of the tumor was positive for cytokeratin 7, cytokeratin 903 (34βE12), and cytokeratin 20. We diagnosed the tumor as urachal cancer and performed surgery. Examination of the resected specimen showed that the tumor was located in the transverse colon. Finally, the patient was diagnosed as having transverse colon cancer with urachal abscess.

Validation of methylation biomarkers that distinguish normal colon mucosa of cancer patients from normal colon mucosa of patients without cancer.

Science.gov (United States)

Cesaroni, Matteo; Powell, Jasmine; Sapienza, Carmen

2014-07-01

We have validated differences in DNA methylation levels of candidate genes previously reported to discriminate between normal colon mucosa of patients with colon cancer and normal colon mucosa of individuals without cancer. Here, we report that CpG sites in 16 of the 30 candidate genes selected show significant differences in mean methylation level in normal colon mucosa of 24 patients with cancer and 24 controls. A support vector machine trained on these data and data for an additional 66 CpGs yielded an 18-gene signature, composed of ten of the validated candidate genes plus eight additional candidates. This model exhibited 96% sensitivity and 100% specificity in a 40-sample training set and classified all eight samples in the test set correctly. Moreover, we found a moderate-strong correlation (Pearson coefficients r = 0.253-0.722) between methylation levels in colon mucosa and methylation levels in peripheral blood for seven of the 18 genes in the support vector model. These seven genes, alone, classified 44 of the 48 patients in the validation set correctly and five CpGs selected from only two of the seven genes classified 41 of the 48 patients in the discovery set correctly. These results suggest that methylation biomarkers may be developed that will, at minimum, serve as useful objective and quantitative diagnostic complements to colonoscopy as a cancer-screening tool. These data also suggest that it may be possible to monitor biomarker methylation levels in tissues collected much less invasively than by colonoscopy. ©2014 American Association for Cancer Research.

Faecal urobilinogen levels and pH of stools in population groups with different incidence of cancer of the colon, and their possible role in its aetiology.

OpenAIRE

Malhotra, S L

1982-01-01

Mean faecal urobilinogen levels and the pH of stools were both found to be higher in subjects from a population group at high risk of developing cancer of the colon than in subjects matched for age, sex and socioeconomic status from a low-risk population group. An alkaline reaction of the colon contents seems to have a tumorigenic effect by a direct action on the mucus of the mucous cells. An acidic reaction, on the other hand, appears to be protective. These differences are dependent on the ...

Association of helicobacter pylori infection and chronic atrophic gastritis with risk of colonic, pancreatic and gastric cancer: A ten-year follow-up of the ESTHER cohort study.

Science.gov (United States)

Chen, Xin-Zu; Schöttker, Ben; Castro, Felipe Andres; Chen, Hongda; Zhang, Yan; Holleczek, Bernd; Brenner, Hermann

2016-03-29

To assess the association of H. pylori and chronic atrophic gastritis (AG) with colonic, pancreatic and gastric cancer in a population-based prospective cohort. Serum antibodies against H. pylori in general and specific to cytotoxin-associated gene A (CagA), as well as serum pepsinogen I and II were analyzed in 9,506 men and women, aged 50-75 years in a cohort study from Saarland, Germany. Incident cases of colonic, pancreatic and gastric cancer were ascertained by record linkage with data from the Saarland Cancer Registry. During an average follow-up of 10.6 years, 108 colonic, 46 pancreatic and 27 gastric incident cancers were recorded. There was no association between H. pylori infection and colonic cancer (HR = 1.07; 95% CI 0.73-1.56) or pancreatic cancer (HR = 1.32; 0.73-2.39), regardless of either CagA seropositivity or AG status. In contrast, CagA+ infection was associated with a strongly increased risk of gastric cancer, especially non-cardia gastric cancer, and this association was particularly pronounced in the presence of AG. Compared to people without AG and without CagA+ infection, people with both risk factors had a significantly increased risk of non-cardia gastric cancer (HR = 32.4; 7.6-137.6). This large cohort study did not observe an association of H. pylori infection or AG with colonic or pancreatic cancer, but underlines that the vast majority of non-cardia gastric cancers arise from AG and infection with CagA+ H. pylori strains.

Drugs Approved for Colon and Rectal Cancer

Science.gov (United States)

This page lists cancer drugs approved by the Food and Drug Administration (FDA) for use in colon cancer and rectal cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

Outcome of Laparoscopic Versus Open Resection for Transverse Colon Cancer.

Science.gov (United States)

Zeng, Wei-Gen; Liu, Meng-Jia; Zhou, Zhi-Xiang; Hou, Hui-Rong; Liang, Jian-Wei; Wang, Zheng; Zhang, Xing-Mao; Hu, Jun-Jie

2015-10-01

Laparoscopic resection for transverse colon cancer remains controversial. The aim of this study is to investigate the short- and long-term outcomes of laparoscopic surgery for transverse colon cancer. A total of 278 patients with transverse colon cancer from a single institution were included. All patients underwent curative surgery, 156 patients underwent laparoscopic resection (LR), and 122 patients underwent open resection (OR). The short- and long-term results were compared between two groups. Baseline demographic and clinical characteristics were comparable between two groups. Conversions were required in eight (5.1 %) patients. LR group was associated with significantly longer median operating time (180 vs. 140 min; P colon cancer is associated with better short-term outcomes and equivalent long-term oncologic outcomes.

microRNA-365, down-regulated in colon cancer, inhibits cell cycle progression and promotes apoptosis of colon cancer cells by probably targeting Cyclin D1 and Bcl-2.

Science.gov (United States)

Nie, Jing; Liu, Lin; Zheng, Wei; Chen, Lin; Wu, Xin; Xu, Yingxin; Du, Xiaohui; Han, Weidong

2012-01-01

Deregulated microRNAs participate in carcinogenesis and cancer progression, but their roles in cancer development remain unclear. In this study, miR-365 expression was found to be downregulated in human colon cancer tissues as compared with that in matched non-neoplastic mucosa tissues, and its downregulation was correlated with cancer progression and poor survival in colon cancer patients. Functional studies revealed that restoration of miR-365 expression inhibited cell cycle progression, promoted 5-fluorouracil-induced apoptosis and repressed tumorigenicity in colon cancer cell lines. Furthermore, bioinformatic prediction and experimental validation were used to identify miR-365 target genes and indicated that the antitumor effects of miR-365 were probably mediated by its targeting and repression of Cyclin D1 and Bcl-2 expression, thus inhibiting cell cycle progression and promoting apoptosis. These results suggest that downregulation of miR-365 in colon cancer may have potential applications in prognosis prediction and gene therapy in colon cancer patients.

Risk of metachronous colon cancer following surgery for rectal cancer in mismatch repair gene mutation carriers.

Science.gov (United States)

Win, Aung Ko; Parry, Susan; Parry, Bryan; Kalady, Matthew F; Macrae, Finlay A; Ahnen, Dennis J; Young, Graeme P; Lipton, Lara; Winship, Ingrid; Boussioutas, Alex; Young, Joanne P; Buchanan, Daniel D; Arnold, Julie; Le Marchand, Loïc; Newcomb, Polly A; Haile, Robert W; Lindor, Noralane M; Gallinger, Steven; Hopper, John L; Jenkins, Mark A

2013-06-01

Despite regular surveillance colonoscopy, the metachronous colorectal cancer risk for mismatch repair (MMR) gene mutation carriers after segmental resection for colon cancer is high and total or subtotal colectomy is the preferred option. However, if the index cancer is in the rectum, management decisions are complicated by considerations of impaired bowel function. We aimed to estimate the risk of metachronous colon cancer for MMR gene mutation carriers who underwent a proctectomy for index rectal cancer. This retrospective cohort study comprised 79 carriers of germline mutation in a MMR gene (18 MLH1, 55 MSH2, 4 MSH6, and 2 PMS2) from the Colon Cancer Family Registry who had had a proctectomy for index rectal cancer. Cumulative risks of metachronous colon cancer were calculated using the Kaplan-Meier method. During median 9 years (range 1-32 years) of observation since the first diagnosis of rectal cancer, 21 carriers (27 %) were diagnosed with metachronous colon cancer (incidence 24.25, 95 % confidence interval [CI] 15.81-37.19 per 1,000 person-years). Cumulative risk of metachronous colon cancer was 19 % (95 % CI 9-31 %) at 10 years, 47 (95 % CI 31-68 %) at 20 years, and 69 % (95 % CI 45-89 %) at 30 years after surgical resection. The frequency of surveillance colonoscopy was 1 colonoscopy per 1.16 years (95 % CI 1.01-1.31 years). The AJCC stages of the metachronous cancers, where available, were 72 % stage I, 22 % stage II, and 6 % stage III. Given the high metachronous colon cancer risk for MMR gene mutation carriers diagnosed with an index rectal cancer, proctocolectomy may need to be considered.

Checkpoint inhibitors in endometrial cancer: preclinical rationale and clinical activity.

Science.gov (United States)

Mittica, Gloria; Ghisoni, Eleonora; Giannone, Gaia; Aglietta, Massimo; Genta, Sofia; Valabrega, Giorgio

2017-10-27

Treatment of advanced and recurrent endometrial cancer (EC) is still an unmet need for oncologists and gynecologic oncologists. The Cancer Genome Atlas Research Network (TCGA) recently provided a new genomic classification, dividing EC in four subgroups. Two types of EC, the polymerase epsilon (POLE)-ultra-mutated and the microsatellite instability-hyper-mutated (MSI-H), are characterized by a high mutation rate providing the rationale for a potential activity of checkpoint inhibitors. We analyzed all available evidence supporting the role of tumor microenvironment (TME) in EC development and the therapeutic implications offered by immune checkpoint inhibitors in this setting. We performed a review on Pubmed with Mesh keywords 'endometrial cancer' and the name of each checkpoint inhibitor discussed in the article. The same search was operated on clinicaltrial.gov to identify ongoing clinical trials exploring PD-1/PD-L1 and CTLA-4 axis in EC, particularly focusing on POLE-ultra-muted and MSI-H cancer types. POLE-ultra-mutated and MSI-H ECs showed an active TME expressing high number of neo-antigens and an elevated amount of tumor infiltrating lymphocytes (TILs). Preliminary results from a phase-1 clinical trial (KEYNOTE-028) demonstrated antitumor activity of Pembrolizumab in EC. Moreover, both Pembrolizumab and Nivolumab reported durable clinical responses in POLE-ultra-mutated patients. Immune checkpoint inhibitors are an attractive option in POLE-ultra-mutated and MSI-H ECs. Future investigations in these subgroups include combinations of checkpoints inhibitors with chemotherapy and small tyrosine kinase inhibitors (TKIs) to enhance a more robust intra-tumoral immune response.

Patients with Acromegaly Presenting with Colon Cancer: A Case Series

Directory of Open Access Journals (Sweden)

Murray B. Gordon

2016-01-01

Full Text Available Introduction. Frequent colonoscopy screenings are critical for early diagnosis of colon cancer in patients with acromegaly. Case Presentations. We performed a retrospective analysis of the incidental diagnoses of colon cancer from the ACCESS trial (ClinicalTrials.gov identifier: NCT01995734. Colon cancer was identified in 2 patients (4.5%. Case  1 patient was a 36-year-old male with acromegaly who underwent transsphenoidal surgery to remove the pituitary adenoma. After surgery, the patient underwent routine colonoscopy screening, which revealed a 40 mm tubular adenoma in the descending colon. A T1N1a carcinoma was surgically removed, and 1 of 22 lymph nodes was positive for metastatic disease, leading to a diagnosis of stage 3 colon cancer. Case  2 patient was a 50-year-old male with acromegaly who underwent transsphenoidal surgery to remove a 2 cm pituitary adenoma. The patient reported severe cramping and lower abdominal pain, and an invasive 8.1 cm3 grade 2 adenocarcinoma with signet rings was identified in the ascending colon and removed. Of the 37 lymph nodes, 34 were positive for the presence of tumor cells, and stage 3c colon cancer was confirmed. Conclusion. Current guidelines for colonoscopy screening at the time of diagnosis of acromegaly and at appropriate follow-up intervals should be followed.

File list: Oth.Dig.20.AllAg.Colon_cancer [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.Dig.20.AllAg.Colon_cancer hg19 TFs and others Digestive tract Colon cancer SRX1...55772,SRX155773,SRX155775,SRX155776 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Dig.20.AllAg.Colon_cancer.bed ...

File list: Oth.Dig.10.AllAg.Colon_cancer [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.Dig.10.AllAg.Colon_cancer hg19 TFs and others Digestive tract Colon cancer SRX1...55772,SRX155775,SRX155773,SRX155776 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Dig.10.AllAg.Colon_cancer.bed ...

File list: Oth.Dig.05.AllAg.Colon_cancer [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.Dig.05.AllAg.Colon_cancer hg19 TFs and others Digestive tract Colon cancer SRX1...55772,SRX155773,SRX155775,SRX155776 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Dig.05.AllAg.Colon_cancer.bed ...

File list: Oth.Dig.50.AllAg.Colon_cancer [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.Dig.50.AllAg.Colon_cancer hg19 TFs and others Digestive tract Colon cancer SRX1...55772,SRX155775,SRX155773,SRX155776 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Dig.50.AllAg.Colon_cancer.bed ...

Preventing Second Cancers in Colon Cancer Survivors

Science.gov (United States)

In this phase III trial, people who have had curative surgery for colon cancer will be randomly assigned to take sulindac and a placebo, eflornithine and a placebo, both sulindac and eflornithine, or two placebo pills for 36 months.

Loss of nuclear p27 (CDKN1B/KIP1) in colorectal cancer is correlated with microsatellite instability and CIMP.

Science.gov (United States)

Ogino, Shuji; Kawasaki, Takako; Kirkner, Gregory J; Yamaji, Taiki; Loda, Massimo; Fuchs, Charles S

2007-01-01

Downregulation of p27 (cyclin-dependent kinase inhibitor-1B, CDKN1B or KIP1) is caused by increased ubiquitin-mediated proteasomal degradation in colorectal cancer, and has been associated with poor prognosis. CpG island methylator phenotype (CIMP) is a phenotype of colorectal cancer with extensive promoter methylation, and associated with high degree of microsatellite instability (MSI-H) and BRAF mutations. We have recently shown that both CIMP and MSI-H are inversely associated with downregulation of p21 (CDKN1A or CIP1), another cyclin-dependent kinase inhibitor. However, no study to date has examined relationship between p27 and CIMP status in colorectal cancer. Using MethyLight assays, we measured DNA methylation in five CIMP-specific gene promoters {CACNA1G, CDKN2A (p16), CRABP1, MLH1 and NEUROG1} in 706 colorectal cancer samples obtained from two large prospective cohorts. Among the 706 tumors, 112 (16%) were CIMP-high tumors with >or=4/5 methylated promoters. We assessed p27 and p53 expressions by immunohistochemistry. Loss of nuclear p27 expression {observed in 231 tumors (33%)} was significantly associated with CIMP-high, MSI-H and BRAF mutations, and these associations were much more pronounced among p53-negative tumors than p53-positive tumors. When CIMP-high and non-CIMP-high tumors were stratified by MSI status (or KRAS and BRAF status), CIMP-high and MSI-H (but not BRAF mutations) were still significantly associated with nuclear p27 loss. Nuclear p27 loss did not appear to be directly related to CDKN2A (p16) methylation. We conclude that downregulation of nuclear p27 is associated with CIMP-high and MSI-H in colorectal cancer. These associations are stronger among p53 wild-type tumors, implying important interplay of p27 and p53 functions (or dysfunctions) in the development of various molecular subtypes of colorectal cancer.

[Evaluation of knowledge about colon cancer prevention versus other tumors].

Science.gov (United States)

Sanguinetti, José María; Henry, Nicolás; Ocaña, Domingo; Polesel, Julio Lotero

2015-06-01

In Argentina almost 7% of deaths are due to different cancers with screening strategies. Evaluate knowledge about cancer prevention compared with other tumors. Materials. A descriptive and comparative study. A survey between April and June 2013 in Salta City, province of Salta, Argentina. Correct answers were considered. Statistical analysis: Descriptive (mean and percentage), comparative Chi square Test (significance level Pmama and cervix. 20% (CI 0,13-0,28) knew that colon cancer has a genetic predisposition and 58% (CI 0,48-0,67) about mama. 73% (CI 0,63-0,8) received information about cancer prevention. The main source of information was the physician. 46% (CI 0,36-0,55) received medical care in private institutions. Those who had social security, higher educational levels and medical care in private institutions had better knowledge about cancer prevention except in colon cancer. The global results showed levels below 70% in general but extremely low in colon cancer. Not having social security, receiving medical care in public institutions and having a low educational level are related with poor knowledge about cancer prevention except for colon and prostate cancer.

Tumor infiltrating lymphocytes: an intriguing player in the survival of colorectal cancer patients

Directory of Open Access Journals (Sweden)

Lardon Filip

2010-04-01

Full Text Available Abstract Background There is growing evidence that both local and systemic inflammatory responses play an important role in the progression of a variety of solid tumors. Colorectal cancer results from the cumulative effect of sequential genetic alterations, leading to the expression of tumor associated antigens possibly inducing a cellular anti-tumor immune response. It is well recognized that cytotoxic lymphocytes constitute one of the most important effector mechanisms of anti-tumor-immunity. However, their potential prognostic influence in colorectal cancer remains controversial. Aim of the study was to examine infiltration of CD3+ and CD8+ lymphocytes in colorectal cancer and their prognostic potential. Two-hundred-fifteen colorectal cancer cases, previously analyzed for microsatellite instability (MSI, were selected for immunohistochemical detection of CD3+, CD8+ infiltration and the expression of granzyme B. Prognostic relevance was assessed by survival analysis. Results Strong correlations were found between the infiltration of lymphocytes and several clinicopathological variables. Survival analysis revealed that intra-epithelial infiltration of CD3+ and CD8+ T lymphocytes and stromal infiltration of CD3+ lymphocytes had a major impact on the patients' overall survival in the univariate analysis, however independent of their association with MSI-status. In addition, it was also demonstrated that there was an important disease specific survival advantage for patients with microsatellite stable (MSS tumors containing intraepithelial CD8+ tumor infiltrating lymphocytes. When samples were analyzed for colon cancer and rectal cancer separately, the results of the overall population were confirmed in colon cancer only. When entered into a multiple Cox regression analysis adjusting for other possible important confounding factors, the strong impact of lymphocyte infiltration on overall survival was not maintained. Only early stage and young age

Survival after elective surgery for colonic cancer in Denmark

DEFF Research Database (Denmark)

Perdawid, S K; Hemmingsen, L; Boesby, S

2012-01-01

AIM: Total mesorectal excision (TME) has been shown to improve the outcome for patients with rectal cancer. In contrast, there are fewer data on complete mesocolic excision (CME) for colonic cancer. METHOD: Data from the National Colorectal Cancer Database were analysed. This includes about 95......% of all patients with colorectal cancer in Denmark. Only patients having elective surgery for colonic cancer in the period 2001-2008 were included. Overall and relative survival analyses were carried out. The study period was divided into the periods 2001-2004 and 2005-2008. RESULTS: 9149 patients were...... included for the final analysis. The overall 5-year survival rates were 0.65 in 2001-2004 and 0.66 in 2005-2008. The relative 5-year survival rates were also within 1% of each other. None of these comparisons was statistically significant. CONCLUSION: Survival following elective colon cancer surgery has...

Oncogenic KRAS activates an embryonic stem cell-like program in human colon cancer initiation.

Science.gov (United States)

Le Rolle, Anne-France; Chiu, Thang K; Zeng, Zhaoshi; Shia, Jinru; Weiser, Martin R; Paty, Philip B; Chiu, Vi K

2016-01-19

Colorectal cancer is the third most frequently diagnosed cancer worldwide. Prevention of colorectal cancer initiation represents the most effective overall strategy to reduce its associated morbidity and mortality. Activating KRAS mutation (KRASmut) is the most prevalent oncogenic driver in colorectal cancer development, and KRASmut inhibition represents an unmet clinical need. We apply a systems-level approach to study the impact of KRASmut on stem cell signaling during human colon cancer initiation by performing gene set enrichment analysis on gene expression from human colon tissues. We find that KRASmut imposes the embryonic stem cell-like program during human colon cancer initiation from colon adenoma to stage I carcinoma. Expression of miR145, an embryonic SC program inhibitor, promotes cell lineage differentiation marker expression in KRASmut colon cancer cells and significantly suppresses their tumorigenicity. Our data support an in vivo plasticity model of human colon cancer initiation that merges the intrinsic stem cell properties of aberrant colon stem cells with the embryonic stem cell-like program induced by KRASmut to optimize malignant transformation. Inhibition of the embryonic SC-like program in KRASmut colon cancer cells reveals a novel therapeutic strategy to programmatically inhibit KRASmut tumors and prevent colon cancer.

Longitudinal changes in lifestyle behaviors and health status in colon cancer survivors.

Science.gov (United States)

Satia, Jessie A; Campbell, Marci K; Galanko, Joseph A; James, Aimee; Carr, Carol; Sandler, Robert S

2004-06-01

Lifestyle changes in persons diagnosed with cancer are important because they may impact prognosis, co-morbidities, and survival. This report describes longitudinal changes in lifestyle behaviors and health status among colon cancer survivors (n = 278) and population-based controls (n = 459) in North Carolina (39% African American), and examines demographic and psychosocial correlates of healthy lifestyle changes following a colon cancer diagnosis. Data are from surveys of a population-based cohort of colon cancer patients on diagnosis (the North Carolina Colon Cancer Study, NCCCS) and approximately 2 years post-diagnosis [the North Carolina Strategies to Improve Diet, Exercise, and Screening Study (NC STRIDES)], and population-based controls. Both studies collected information on demographic/lifestyle characteristics and medical history. The NCCCS reflects pre-diagnosis or pre-interview patterns, whereas NC STRIDES queried on current practices. Between the NCCCS and NC STRIDES, colon cancer survivors reported significant increases in vegetable intake, physical activity, and supplement use (all P dietary supplement post-diagnosis, whereas being retired correlated with increased vegetable intake, all P Colon cancer survivors reported making significant improvements in multiple health-related behaviors. Health care providers should communicate with persons diagnosed with colon cancer to ensure that they are making healthy lifestyle changes.

Correlation between the methylation of APC gene promoter and colon cancer.

Science.gov (United States)

Li, Bing-Qiang; Liu, Peng-Peng; Zhang, Cai-Hua

2017-08-01

The present study was planned to explore the correlation between the methylation of APC (adenomatous polyposis coli) and colon carcinogenesis. Colon cancer tissues and tumor-adjacent normal tissues of 60 colon cancer patients (who received surgical operation in our hospital from January 2012 to December 2014) were collected. SW1116 cells in human colon cancer tissues were selected for culturing. 5-aza-2c-deoxycytidine (5-aza-dC) was utilized as an inhibitor of the methylation for APC gene. Methylation specific PCR (MSP) was utilized for detection of APC methylation in SW1116 cells. The MTT and Transwell assays were performed to detect the effect of the methylation of APC gene on the proliferation and invasive abilities of SW1116 cells. The correlation between the methylation of APC gene and pathological parameters of colon cancer patients was analyzed. MSP results revealed that 41 cases (68.33%) showed methylation of APC gene in colon cancer tissues. No methylation of APC gene was found in tumor-adjacent normal tissues. 5-aza-dC was able to inhibit the methylation of APC gene in SW1116 cells. APC gene methylation was correlated with tumor size, differentiation degree, lymph node metastasis and Dukes staging. In conclusion, the levels of the methylation of APC in colon cancer tissues and SW1116 cells are relatively high. The methylation of APC promoted the proliferation and invasion abilities of SW1116 cells. Furthermore, methylation is correlated with a variety of clinicopathological features of colon cancer patients.

Elderly patients with colon cancer have unique tumor characteristics and poor survival.

Science.gov (United States)

Patel, Supriya S; Nelson, Rebecca; Sanchez, Julian; Lee, Wendy; Uyeno, Lori; Garcia-Aguilar, Julio; Hurria, Arti; Kim, Joseph

2013-02-15

The incidence of colon cancer increases with age, and colon cancer predominantly affects individuals >65 years old. However, there are limited data regarding clinical and pathologic factors, treatment characteristics, and survival of older patients with colon cancer. The objective of this study was to determine the effects of increasing age on colon cancer. Patients diagnosed with colon cancer between 1988 and 2006 were identified through the Los Angeles County Cancer Surveillance Program, in Southern California. Patients were stratified into 4 age groups: 18-49, 50-64, 65-79, and ≥80 years. Clinical and pathologic characteristics and disease-specific and overall survival were compared between patients from different age groups. A total of 32,819 patients were assessed. Patients aged 18 to 49 and 65 to 79 years represented the smallest and largest groups, respectively. A near equal number of males and females were diagnosed with colon cancer in the 3 youngest age groups, whereas patients who were ≥80 years old were more commonly white and female. Tumor location was different between groups, and the frequency of larger tumors (>5 cm) was greatest in youngest patients (18-49 years). The oldest patients (≥80 years) were administered chemotherapy at the lowest frequency, and disease-specific and overall survival rates decreased with increasing age. This investigation demonstrates that older age is associated with alterations in clinical and pathologic characteristics and decreased survival. This suggests that the phenotype of colon cancer and the efficacy of colon cancer therapies may be dependent on the age of patients. Copyright © 2012 American Cancer Society.

Epsin is required for Dishevelled stability and Wnt signalling activation in colon cancer development.

Science.gov (United States)

Chang, Baojun; Tessneer, Kandice L; McManus, John; Liu, Xiaolei; Hahn, Scott; Pasula, Satish; Wu, Hao; Song, Hoogeun; Chen, Yiyuan; Cai, Xiaofeng; Dong, Yunzhou; Brophy, Megan L; Rahman, Ruby; Ma, Jian-Xing; Xia, Lijun; Chen, Hong

2015-03-16

Uncontrolled canonical Wnt signalling supports colon epithelial tumour expansion and malignant transformation. Understanding the regulatory mechanisms involved is crucial for elucidating the pathogenesis of and will provide new therapeutic targets for colon cancer. Epsins are ubiquitin-binding adaptor proteins upregulated in several human cancers; however, the involvement of epsins in colon cancer is unknown. Here we show that loss of intestinal epithelial epsins protects against colon cancer by significantly reducing the stability of the crucial Wnt signalling effector, dishevelled (Dvl2), and impairing Wnt signalling. Consistently, epsins and Dvl2 are correspondingly upregulated in colon cancer. Mechanistically, epsin binds Dvl2 via its epsin N-terminal homology domain and ubiquitin-interacting motifs and prohibits Dvl2 polyubiquitination and degradation. Our findings reveal an unconventional role for epsins in stabilizing Dvl2 and potentiating Wnt signalling in colon cancer cells to ensure robust colon cancer progression. The pro-carcinogenic role of Epsins suggests that they are potential therapeutic targets to combat colon cancer.

Noscapine induces mitochondria-mediated apoptosis in human colon cancer cells in vivo and in vitro

International Nuclear Information System (INIS)

Yang, Zi-Rong; Liu, Meng; Peng, Xiu-Lan; Lei, Xiao-Fei; Zhang, Ji-Xiang; Dong, Wei-Guo

2012-01-01

Highlights: ► Noscapine inhibited cell viability of colon cancer in a time- and dose- dependent manner. ► G 2 /M phase arrest and chromatin condensation and nuclear fragmentation were induced. ► Noscapine promoted apoptosis via mitochondrial pathways. ► Tumorigenicity was inhibited by noscapine. -- Abstract: Noscapine, a phthalide isoquinoline alkaloid derived from opium, has been widely used as a cough suppressant for decades. Noscapine has recently been shown to potentiate the anti-cancer effects of several therapies by inducing apoptosis in various malignant cells without any detectable toxicity in cells or tissues. However, the mechanism by which noscapine induces apoptosis in colon cancer cells remains unclear. The signaling pathways by which noscapine induces apoptosis were investigated in colon cancer cell lines treated with various noscapine concentrations for 72 h, and a dose-dependent inhibition of cell viability was observed. Noscapine effectively inhibited the proliferation of LoVo cells in vitro (IC 50 = 75 μM). This cytotoxicity was reflected by cell cycle arrest at G 2 /M and subsequent apoptosis, as indicated by increased chromatin condensation and fragmentation, the upregulation of Bax and cytochrome c (Cyt-c), the downregulation of survivin and Bcl-2, and the activation of caspase-3 and caspase-9. Moreover, in a xenograft tumor model in mice, noscapine injection clearly inhibited tumor growth via the induction of apoptosis, which was demonstrated using a TUNEL assay. These results suggest that noscapine induces apoptosis in colon cancer cells via mitochondrial pathways. Noscapine may be a safe and effective chemotherapeutic agent for the treatment of human colon cancer.

In vitro evaluation of antiproliferative and cytotoxic properties of pterostilbene against human colon cancer cells.

Science.gov (United States)

Wawszczyk, Joanna; Kapral, Małgorzata; Hollek, Andrzej; Węglarz, Ludmiła

2014-01-01

Colon cancer has been remaining the second leading cause of cancer mortality in Poland in the last years. Epidemiological, preclinical and clinical studies reveal that dietary phytochemicals may exert chemopreventive and therapeutic effect against colorectal cancer. There is a growing interest in identifying new biologically active agents from dietary sources in this respect. Pterostilbene (trans-3,5-dimethoxy-4-hydroxystilbene) is a naturally occurring stilbene, that has been found to have antioxidative, anti-inflammatory and antipro- liferative properties. Compared to other stilbenes, pterostilbene has greater bioavailability, and so, a greater potential for clinical applications. Recent studies showed that pterostilbene exhibits the hallmark characteristics of an anticancer agent. The aim of this study was to analyze antiproliferative and cytotoxic effects of pterostilbene on human colon cancer Caco-2 cells. They were cultured using standard techniques and exposed to increasing doses of pterostilbene (5-100 μM) for 48 and 72 h. Cell proliferation was determined by sulforhodamine B assay. The growth of treated cells was expressed as a percentage of that of untreated control cells. Pterostilbene decreased proliferation rate of Caco-2 cells in a dose- and time-dependent manner. Its concentrations = 25 μM did not affect cell growth after 48 h treatment period. Significant growth inhibition was observed in cultures incubated with higher concentrations of pterostilbene (40-100 μM). Pterostilbene at all concentrations used (5-100 μM) caused significant inhibition of cell proliferation when the experimental time period was elongated to 72 h. The maximum growth reduction was observed at 100 mM pterostilbene. The cytotoxicity of pterostilbene was evaluated in 48 h cultures based on lactate dehydrogenase (LDH) leakage into the culture medium and showed dose-related pattern. The findings of this study showed significant dose-dependent antiproliferative and cytotoxic

In vitro radiosensitization by oxaliplatin and 5-fluorouracil in a human colon cancer cell line

International Nuclear Information System (INIS)

Kjellstroem, Johan; Kjellen, Elisabeth; Johnsson, Anders

2005-01-01

The current study was designed to compare the radiosensitizing effects of oxaliplatin and 5-fluorouracil (5FU) in a human colon cancer cell line. A human colon cancer cell line (S1) was treated with various doses of oxaliplatin, 5FU, radiation, and combinations thereof. Various clinically used schedules were mimicked. 5FU was either incubated during 1 h ('bolus') or 24 h ('continuous infusion'). When combining oxaliplatin and 5FU, an isobologram analysis revealed synergistic effects, regardless of 5FU schedule. The IC 10 and IC 50 -doses for the drugs where then combined with radiotherapy. With equitoxic drug doses (IC 50 ), radiosensitization was observed in the following order: oxaliplatin>5FU 24 h>5FU 1 h exposure. The degree of potentiation corresponded to approximately 0.8 Gy, 0.7 Gy, and 0.2 Gy, respectively. In this experimental setting, oxaliplatin seemed to be a better radiosensitizer than 5FU, and longer incubation time with 5FU was better than short exposure

Associations between birth weight and colon and rectal cancer risk in adulthood.

Science.gov (United States)

Smith, Natalie R; Jensen, Britt W; Zimmermann, Esther; Gamborg, Michael; Sørensen, Thorkild I A; Baker, Jennifer L

2016-06-01

Birth weight has inconsistent associations with colorectal cancer, possibly due to different anatomic features of the colon versus the rectum. The aim of this study was to investigate the association between birth weight and colon and rectal cancers separately. 193,306 children, born from 1936 to 1972, from the Copenhagen School Health Record Register were followed prospectively in Danish health registers. Colon and rectal cancer cases were defined using the International Classification of Disease version 10 (colon: C18.0-18.9, rectal: 19.9 and 20.9). Only cancers classified as adenocarcinomas were included in the analyses. Cox regressions were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Analyses were stratified by birth cohort and sex. During 3.8 million person-years of follow-up, 1465 colon and 961 rectal adenocarcinomas were identified. No significant sex differences were observed; therefore combined results are presented. Birth weight was positively associated with colon cancers with a HR of 1.14 (95% CI, 1.04-1.26) per kilogram of birth weight. For rectal cancer a significant association was not observed for birth weights below 3.5kg. Above 3.5kg an inverse association was observed (at 4.5kg, HR=0.77 [95% CI, 0.61-0.96]). Further, the associations between birth weight and colon and rectal cancer differed significantly from each other (p=0.006). Birth weight is positively associated with the risk of adult colon cancer, whereas the results for rectal cancer were inverse only above values of 3.5kg. The results underline the importance of investigating colon and rectal cancer as two different entities. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Prophylactic effects of triptolide on colon cancer development in ...

African Journals Online (AJOL)

Purpose: To investigate effects of triptolide on colon cancer cell growth and its capacity to prevent tumor development in an azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model of colon cancer. Methods: HCT116 cell viability and migration potential were assessed. Control and AOM/DSS-treated mice (with and ...

Genetic variation in 15-hydroxyprostaglandin dehydrogenase and colon cancer susceptibility.

Directory of Open Access Journals (Sweden)

Cheryl L Thompson

Full Text Available 15-Hydroxyprostaglandin dehydrogenase (15-PGDH is a metabolic antagonist of COX-2, catalyzing the degradation of inflammation mediator prostaglandin E2 (PGE2 and other prostanoids. Recent studies have established the 15-PGDH gene as a colon cancer suppressor.We evaluated 15-PDGH as a colon cancer susceptibility locus in a three-stage design. We first genotyped 102 single-nucleotide polymorphisms (SNPs in the 15-PGDH gene, spanning ∼50 kb up and down-stream of the coding region, in 464 colon cancer cases and 393 population controls. We then genotyped the same SNPs, and also assayed the expression levels of 15-PGDH in colon tissues from 69 independent patients for whom colon tissue and paired germline DNA samples were available. In the final stage 3, we genotyped the 9 most promising SNPs from stages 1 and 2 in an independent sample of 525 cases and 816 controls (stage 3.In the first two stages, three SNPs (rs1365611, rs6844282 and rs2332897 were statistically significant (p<0.05 in combined analysis of association with risk of colon cancer and of association with 15-PGDH expression, after adjustment for multiple testing. For one additional SNP, rs2555639, the T allele showed increased cancer risk and decreased 15-PGDH expression, but just missed statistical significance (p-adjusted = 0.063. In stage 3, rs2555639 alone showed evidence of association with an odds ratio (TT compared to CC of 1.50 (95% CI = 1.05-2.15, p = 0.026.Our data suggest that the rs2555639 T allele is associated with increased risk of colon cancer, and that carriers of this risk allele exhibit decreased expression of 15-PGDH in the colon.

Survival of patients with colon and rectal cancer in central and northern Denmark, 1998–2009

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Ostenfeld EB

2011-07-01

Full Text Available Eva B Ostenfeld1, Rune Erichsen1, Lene H Iversen1,2, Per Gandrup3, Mette Nørgaard1, Jacob Jacobsen11Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 2Department of Surgery P, Aarhus University Hospital, Aarhus, Denmark; 3Department of Surgery A, Aarhus University Hospital, Aalborg, DenmarkObjective: The prognosis for colon and rectal cancer has improved in Denmark over the past decades but is still poor compared with that in our neighboring countries. We conducted this population-based study to monitor recent trends in colon and rectal cancer survival in the central and northern regions of Denmark.Material and methods: Using the Danish National Registry of Patients, we identified 9412 patients with an incident diagnosis of colon cancer and 5685 patients diagnosed with rectal cancer between 1998 and 2009. We determined survival, and used Cox proportional hazard regression analysis to compare mortality over time, adjusting for age and gender. Among surgically treated patients, we computed 30-day mortality and corresponding mortality rate ratios (MRRs.Results: The annual numbers of colon and rectal cancer increased from 1998 through 2009. For colon cancer, 1-year survival improved from 65% to 70%, and 5-year survival improved from 37% to 43%. For rectal cancer, 1-year survival improved from 73% to 78%, and 5-year survival improved from 39% to 47%. Men aged 80+ showed most pronounced improvements. The 1- and 5-year adjusted MRRs decreased: for colon cancer 0.83 (95% confidence interval CI: 0.76–0.92 and 0.84 (95% CI: 0.78–0.90 respectively; for rectal cancer 0.79 (95% CI: 0.68–0.91 and 0.81 (95% CI: 0.73–0.89 respectively. The 30-day postoperative mortality after resection also declined over the study period. Compared with 1998–2000 the 30-day MRRs in 2007–2009 were 0.68 (95% CI: 0.53–0.87 for colon cancer and 0.59 (95% CI: 0.37–0.96 for rectal cancer.Conclusion: The survival after colon and rectal

Down-regulation of LRP1B in colon cancer promoted the growth and migration of cancer cells.

Science.gov (United States)

Wang, Zhiqiang; Sun, Peng; Gao, Chun; Chen, Ji; Li, Jun; Chen, Zhonghao; Xu, Ming; Shao, Jun; Zhang, Yunpeng; Xie, Jiang

2017-08-01

Aberrant activation of beta-catenin/TCF signaling is one of the hallmarks of colon cancer. It is of great interest to study the mechanism for the regulation of beta-catenin/TCF signaling. In this study, it was found that LRP1B was down-regulated in colon cancer tissues and inhibited the growth, migration and metastasis of colon cancer cells. The molecular mechanism study revealed that LRP1B interacted with DVL2, inhibited the interaction between DVL2 and Axin, and negatively regulated beta-catenin/TCF signaling. Taken together, our study demonstrated the suppressive roles of LRP1B in the progression of colon cancer, implicating that restoring the function of LRP1B would be a promising strategy for the treatment of colon cancer. Copyright © 2017. Published by Elsevier Inc.

Current management of liver metastases of colon cancer

International Nuclear Information System (INIS)

Mainieri Breedy, Giovanna

2010-01-01

Colon cancer has been one of the major tumors in the world, both men and women; and it is constituted the third most commonly diagnosed tumor, with approximately 1.2 million of new cases per year. This cancer type is considered of great importance in Costa Rica and has occupied the fifth place. Age is the main risk factor, followed by environmental, diabetic and genetic factors. An IV colon cancer has been manifested with any T, with any N and metastases. Metastases from colon cancer to liver can be classified according to whether have been synchronous (20 to 25%) or metachronous (15 to 29%). In turn, they can be synchronous, resectable or unresectable or mechanical resectable or unresectable. The liver has been the most common site of metastases, and the status of this organ has been an important determinant of overall survival in patients with advanced disease. Half of the patients developed metastases during the course of the disease. Metastases has represented the leading cause of death from this tumor. With the advent of new surgical techniques, new anesthetic care, new chemotherapeutic and molecular agents, together with new radiofrequency modalities and ablative treatment, the approach of metastases from colon cancer to the liver has been shown to be decisive in the prolongation of survival of the patient, who in the past was considered a terminal patient [es

Clinical issues in the surgical treatment of colon cancer

NARCIS (Netherlands)

Amri, R.

2015-01-01

More than half of colon cancer patients will eventually die of their disease. Early detection is crucial to maximize chances of cure, as five-year survival can range from 97% to as low as 8% depending on disease stage at diagnosis. Since colon cancer is associated with both old age and obesity,

Diverticular disease and the risk of colon cancer - a population-based case-control study.

Science.gov (United States)

Granlund, J; Svensson, T; Granath, F; Hjern, F; Ekbom, A; Blomqvist, P; Schmidt, P T

2011-09-01

Colon cancer and diverticular disease are most common in the Western world and their incidences tend to increase with advancing age. The association between the diseases remains unclear. To analyse the risk of colon cancer after hospitalisation for diverticular disease. Nationwide case-control study. A total of 41,037 patients with colon cancer during 1992-2006, identified from the Swedish Cancer Register were included. Each case was matched with two control subjects. From the Swedish Inpatient Register, cases and control subjects hospitalised for diverticular disease were identified. Odds ratios (OR) and confidence intervals for receiving a diagnosis of colon cancer after hospital discharge for diverticular disease were calculated. Colon cancer mortality was compared between patients with or without diverticular disease. Within 6months after an admission due to diverticular disease, OR of having a colon cancer diagnosis were up to 31.49 (19.00-52.21). After 12 months, there was no increased risk. The number of discharges for diverticular disease did not affect the risk. Colon cancer mortality did not differ between patients with and without diverticular disease. Diverticular disease does not increase the risk of colon cancer in the long term, and a history of diverticular disease does not affect colon cancer mortality. The increased risk of colon cancer within the first 12months after diagnosing diverticular disease is most likely due to surveillance and misclassification. Examination of the colon should be recommended after a primary episode of symptomatic diverticular disease. © 2011 Blackwell Publishing Ltd.

Prospective weight change and colon cancer risk in male US health professionals

DEFF Research Database (Denmark)

Thygesen, Lau Caspar; Grønbaek, Morten; Johansen, Christoffer

2008-01-01

Epidemiological studies are remarkably consistent, especially among men, in showing that overweight and obesity [body mass index (BMI) >25] are associated with increased risk of colon cancer. However, no prospective studies address the influence of weight change in adulthood on subsequent colon...... cancer risk. In this study, we investigated whether weight change influences colon cancer risk utilizing prospectively collected weight data. We included 46,349 men aged 40-75 participating in the Health Professionals Follow-Up Study. Questionnaires including items on weight were completed every second......-year period, we documented 765 cases of colon cancer. Cumulative mean BMI >22.5 was associated with significantly increased risk of colon cancer. The short-term weight change in the prior 2 to 4 years was positively and significantly associated with risk [HR = 1.14 (95% confidence interval, 1...

Eating patterns and risk of colon cancer.

Science.gov (United States)

Slattery, M L; Boucher, K M; Caan, B J; Potter, J D; Ma, K N

1998-07-01

Colon cancer has been associated with several nutrients and foods. The authors used data from a population-based study conducted in Northern California, Utah, and Minnesota to examine associations between dietary eating patterns and risk of developing colon cancer. Through factor analysis, detailed dietary intake data obtained from 1,993 cases (diagnosed in 1991-1994) and 2,410 controls were grouped into factors that were evaluated for relations with lifestyle characteristics and colon cancer risk. Several dietary patterns emerged. The dietary patterns with the most variation were labeled "Western," "prudent," "high fat/sugar dairy," "substituters," and "drinkers." The "Western" dietary pattern was associated with a higher body mass index and a greater intake of total energy and dietary cholesterol. The "prudent" pattern was associated with higher levels of vigorous leisure time physical activity, smaller body size, and higher intakes of dietary fiber and folate. Persons who had high scores on the "drinker" pattern were also more likely to smoke cigarettes. The "Western" dietary pattern was associated with an increased risk of colon cancer in both men and women. The association was strongest among people diagnosed prior to age 67 years (for men, odds ratio (OR)=1.96, 95% confidence interval (CI) 1.22-3.15; for women, OR=2.02, 95% CI 1.21-3.36) and among men with distal tumors (OR=2.25, 95% CI 1.47-3.46). The "prudent" diet was protective, with the strongest associations being observed among people diagnosed prior to age 67 years (men: OR=0.63, 95% CI 0.43-0.92; women: OR=0.58, 95% CI 0.38-0.87); associations with this dietary pattern were also strong among persons with proximal tumors (men: OR=0.55, 95% CI 0.38-0.80; women: OR=0.64, 95% CI 0.45-0.92). Although "substituters" (people who substituted low fat dairy products for high fat dairy products, margarine for butter, poultry for red meat, and whole grains for refined grains) were at reduced risk of colon cancer

PGE2-induced colon cancer growth is mediated by mTORC1

International Nuclear Information System (INIS)

Dufour, Marc; Faes, Seraina; Dormond-Meuwly, Anne; Demartines, Nicolas; Dormond, Olivier

2014-01-01

Highlights: • PGE 2 activates mTORC1 in colon cancer cells. • Inhibition of mTORC1 blocks PGE 2 induced colon cancer cell growth. • mTORC1 is a signaling intermediary in PGE 2 induced colon cancer cell responses. - Abstract: The inflammatory prostaglandin E 2 (PGE 2 ) cytokine plays a key role in the development of colon cancer. Several studies have shown that PGE 2 directly induces the growth of colon cancer cells and furthermore promotes tumor angiogenesis by increasing the production of the vascular endothelial growth factor (VEGF). The signaling intermediaries implicated in these processes have however not been fully characterized. In this report, we show that the mechanistic target of rapamycin complex 1 (mTORC1) plays an important role in PGE 2 -induced colon cancer cell responses. Indeed, stimulation of LS174T cells with PGE 2 increased mTORC1 activity as observed by the augmentation of S6 ribosomal protein phosphorylation, a downstream effector of mTORC1. The PGE 2 EP 4 receptor was responsible for transducing the signal to mTORC1. Moreover, PGE 2 increased colon cancer cell proliferation as well as the growth of colon cancer cell colonies grown in matrigel and blocking mTORC1 by rapamycin or ATP-competitive inhibitors of mTOR abrogated these effects. Similarly, the inhibition of mTORC1 by downregulation of its component raptor using RNA interference blocked PGE 2 -induced LS174T cell growth. Finally, stimulation of LS174T cells with PGE 2 increased VEGF production which was also prevented by mTORC1 inhibition. Taken together, these results show that mTORC1 is an important signaling intermediary in PGE 2 mediated colon cancer cell growth and VEGF production. They further support a role for mTORC1 in inflammation induced tumor growth

Chemoembolization Using Irinotecan in Treating Patients With Liver Metastases From Metastatic Colon or Rectal Cancer

Science.gov (United States)

2015-09-10

Liver Metastases; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IV Colon Cancer; Stage IV Rectal Cancer

Luteolin inhibits the colon cancer HT-29 cell proliferation, migration and epithelial-mesenchymal transition: an experimental study

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Xin Meng

2017-11-01

Full Text Available Objective: To study the regulating effect of luteolin on colon cancer HT-29 cell proliferation, migration and epithelial-mesenchymal transition. Methods: Colon cancer HT-29 cells were cultured and randomly divided into two groups, control group were treated with serum-free medium without drugs and LUT group were treated with serum-free medium containing luteolin. After 24 h of treatment, cells were collected to extract RNA, and then fluorescent quantitative PCR method was used to determine the mRNA expression of proliferation genes, migration genes and epithelial-mesenchymal transition genes. Results: After 24 h of luteolin treatment, Lrig1, TSPYL5, Bim, SOX15 and DLC1 mRNA expression in LUT group were significantly higher than those in control group while RPS15a, Bad, TRPV5, TRPV6, PLD2, IBP, SphK1, FAK, Vimentin and N-cadherin mRNA expression were significantly lower than those in control group. Conclusion: Luteolin has inhibiting effect on colon cancer HT-29 cell proliferation, migration and epithelial-mesenchymal transition.

Validation of methylation biomarkers that distinguish normal colon mucosa from cancer patients from normal colon mucosa of patients without cancer

Science.gov (United States)

Cesaroni, Matteo; Powell, Jasmine; Sapienza, Carmen

2014-01-01

We have validated differences in DNA methylation levels of candidate genes previously reported to discriminate between normal colon mucosa of colon cancer patients and normal colon mucosa of individuals without cancer. Here, we report that CpG sites in 16 of the 30 candidate genes selected show significant differences in mean methylation level in normal colon mucosa of 24 cancer patients and 24 controls. A support vector machine trained on these data and data for an additional 66 CpGs yielded an 18-gene signature, composed of 10 of the validated candidate genes plus eight additional candidates. This model exhibited 96% sensitivity and 100% specificity in a 40-sample training set and classified all eight samples in the test set correctly. Moreover, we found a moderate-strong correlation (Pearson coefficients r=0.253-0.722) between methylation levels in colon mucosa and methylation levels in peripheral blood for seven of the 18 genes in the support vector model. These seven genes, alone, classified 44 of the 48 patients in the validation set correctly and five CpGs selected from only two of the seven genes classified 41 of the 48 patients in the discovery set correctly. These results suggest that methylation biomarkers may be developed that will, at minimum, serve as useful objective and quantitative diagnostic complements to colonoscopy as a cancer-screening tool. These data also suggest that it may be possible to monitor biomarker methylation levels in tissues collected much less invasively than by colonoscopy. PMID:24806665

Role of phytochemicals in colon cancer prevention. A nutrigenomics approach

NARCIS (Netherlands)

Erk, van M.J.

2004-01-01

Specific food compounds, especially from fruits and vegetables, may protect against development of colon cancer. In this thesis effects and mechanisms of various phytochemicals in relation to colon cancer prevention were studied through application of large-scale gene expression profiling.

Liver X receptor ligand cytotoxicity in colon cancer cells and not in normal colon epithelial cells depends on LXRβ subcellular localization.

Science.gov (United States)

Courtaut, Flavie; Derangère, Valentin; Chevriaux, Angélique; Ladoire, Sylvain; Cotte, Alexia K; Arnould, Laurent; Boidot, Romain; Rialland, Mickaël; Ghiringhelli, François; Rébé, Cédric

2015-09-29

Increasing evidence indicates that Liver X Receptors (LXRs) have some anticancer properties. We recently demonstrated that LXR ligands induce colon cancer cell pyroptosis through an LXRβ-dependent pathway. In the present study, we showed that human colon cancer cell lines presented differential cytoplasmic localizations of LXRβ. This localization correlated with caspase-1 activation and cell death induction under treatment with LXR ligand. The association of LXRβ with the truncated form of RXRα (t-RXRα) was responsible for the sequestration of LXRβ in the cytoplasm in colon cancer cells. Moreover t-RXRα was not expressed in normal colon epithelial cells. These cells presented a predominantly nuclear localization of LXRβ and were resistant to LXR ligand cytotoxicity. Our results showed that predominant cytoplasmic localization of LXRβ, which occurs in colon cancer cells but not in normal colon epithelial cells, allowed LXR ligand-induced pyroptosis. This study strengthens the hypothesis that LXRβ could be a promising target in cancer therapy.

Cryptogenic pyogenic liver abscess as the herald of colon cancer.

Science.gov (United States)

Jeong, Soung Won; Jang, Jae Young; Lee, Tae Hee; Kim, Hyun Gun; Hong, Sung Wook; Park, Seung Hoon; Kim, Sang Gyune; Cheon, Young Koog; Kim, Young Seok; Cho, Young Deok; Kim, Jin-Oh; Kim, Boo Sung; Lee, Eun Jung; Kim, Tae Hyong

2012-02-01

Colonic mucosal defects might be a route for bacterial invasion into the portal system, with subsequent hematogenous spread to the liver. We retrospectively investigated the results of colonoscopy and the clinical characteristics of patients with pyogenic liver abscess of colonic origin. A total of 230 consecutive patients with pyogenic liver abscess were reviewed between 2003 and 2010. The 230 patients were categorized into three groups (pancreatobiliary [n = 135], cryptogenic [n = 81], and others [n = 14]). Of the 81 cryptogenic patients, 37 (45.7%) underwent colonoscopy. Colonic lesions with mucosal defects were considered colonic causes of abscess. In the 37 colonoscopic investigations, colon cancer was found in six patients (16.2%), laterally-spreading tumor (LST) in two patients (5.4%), multiple colon ulcers in one patient (2.7%), colon polyps in 17 patients (45.9%), and diverticula in four patients (10.8%). Nine (11%) of 81 cryptogenic abscesses were therefore reclassified as being of colonic origin (colon cancer = 6, LST = 2, ulcer = 1). Three cases were stage III colon cancer, and the others were stage I. Two LST were high-grade dysplasia. The percentage of patients with Klebsiella pneumoniae (K. pneumoniae) and diabetes mellitus (DM) of colonic origin was 66.7%, which was significantly higher than the 8.6% for other causes (P colonic cause. Colonoscopy should be considered for the detection of hidden colonic malignant lesions in patients with cryptogenic pyogenic liver abscess, especially for patients with K. pneumoniae and DM. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Short-term outcomes following laparoscopic resection for colon cancer.

LENUS (Irish Health Repository)

Kavanagh, Dara O

2011-03-01

Laparoscopic resection for colon cancer has been proven to have a similar oncological efficacy compared to open resection. Despite this, it is performed by a minority of colorectal surgeons. The aim of our study was to evaluate the short-term clinical, oncological and survival outcomes in all patients undergoing laparoscopic resection for colon cancer.

CpG island methylator phenotype is an independent predictor of survival after curative resection for colorectal cancer: A prospective cohort study.

Science.gov (United States)

Kim, Chang Hyun; Huh, Jung Wook; Kim, Hyeong Rok; Kim, Young Jin

2017-08-01

The CpG island methylator phenotype (CIMP) is found in approximately 30% of colorectal cancer (CRC) cases. However, the role of CIMP status in predicting oncologic outcomes in curatively resected CRC is still unclear. Between January 2006 and December 2006, we retrospectively reviewed 157 consecutive patients who underwent curative surgery for CRC. Prognostic significance of CIMP status was evaluated using reverse transcriptase-polymerase chain reaction. CIMP-high (H) and CIMP-none/low (N/L) tumors were found in 50 cases (31.8%) and 107 cases (68.2%), respectively. CIMP-H tumors were significantly associated with female sex, colonic location, poorly/mucinous histologic type, higher T category, perineural invasion, and MSI-high status (P = 0.001). During a median of 64.5 months, tumor recurrence developed in 47 (29.9%) patients. The 5-year disease-free survival for CIMP-H and CIMP-N/L was 61.4% and 76.3% (P = 0.018). In addition, multivariate analysis showed that CIMP-H was also a significant prognostic factor (P = 0.042). When analysis was performed according to anatomical location, more marked survival differences were observed in patients with colon cancer (P = 0.026) than in patients with rectal cancer (P = 0.210). Similarly, the role of CIMP status as a prognostic indicator was more prominent in patients with stage I/II (P = 0.006) than in patients with stage III/IV CRC (P = 0.65). DNA methylation status can be considered as a useful predictor of survival after CRC surgery, particularly for patients with stage I/II disease or colon cancer. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Activin and TGFβ use diverging mitogenic signaling in advanced colon cancer

OpenAIRE

Bauer, Jessica; Ozden, Ozkan; Akagi, Naomi; Carroll, Timothy; Principe, Daniel R.; Staudacher, Jonas J.; Spehlmann, Martina E.; Eckmann, Lars; Grippo, Paul J.; Jung, Barbara

2015-01-01

Background Understanding cell signaling pathways that contribute to metastatic colon cancer is critical to risk stratification in the era of personalized therapeutics. Here, we dissect the unique involvement of mitogenic pathways in a TGFβ or activin-induced metastatic phenotype of colon cancer. Method Mitogenic signaling/growth factor receptor status and p21 localization were correlated in primary colon cancers and intestinal tumors from either AOM/DSS treated ACVR2A (activin receptor 2) −/−...

Genetic variation in selenoprotein genes, lifestyle, and risk of colon and rectal cancer.

Directory of Open Access Journals (Sweden)

Martha L Slattery

Full Text Available BACKGROUND: Associations between selenium and cancer have directed attention to role of selenoproteins in the carcinogenic process. METHODS: We used data from two population-based case-control studies of colon (n = 1555 cases, 1956 controls and rectal (n = 754 cases, 959 controls cancer. We evaluated the association between genetic variation in TXNRD1, TXNRD2, TXNRD3, C11orf31 (SelH, SelW, SelN1, SelS, SepX, and SeP15 with colorectal cancer risk. RESULTS: After adjustment for multiple comparisons, several associations were observed. Two SNPs in TXNRD3 were associated with rectal cancer (rs11718498 dominant OR 1.42 95% CI 1.16,1.74 pACT 0.0036 and rs9637365 recessive 0.70 95% CI 0.55,0.90 pACT 0.0208. Four SNPs in SepN1 were associated with rectal cancer (rs11247735 recessive OR 1.30 95% CI 1.04,1.63 pACT 0.0410; rs2072749 GGvsAA OR 0.53 95% CI 0.36,0.80 pACT 0.0159; rs4659382 recessive OR 0.58 95% CI 0.39,0.86 pACT 0.0247; rs718391 dominant OR 0.76 95% CI 0.62,0.94 pACT 0.0300. Interaction between these genes and exposures that could influence these genes showed numerous significant associations after adjustment for multiple comparisons. Two SNPs in TXNRD1 and four SNPs in TXNRD2 interacted with aspirin/NSAID to influence colon cancer; one SNP in TXNRD1, two SNPs in TXNRD2, and one SNP in TXNRD3 interacted with aspirin/NSAIDs to influence rectal cancer. Five SNPs in TXNRD2 and one in SelS, SeP15, and SelW1 interacted with estrogen to modify colon cancer risk; one SNP in SelW1 interacted with estrogen to alter rectal cancer risk. Several SNPs in this candidate pathway influenced survival after diagnosis with colon cancer (SeP15 and SepX1 increased HRR and rectal cancer (SepX1 increased HRR. CONCLUSIONS: Findings support an association between selenoprotein genes and colon and rectal cancer development and survival after diagnosis. Given the interactions observed, it is likely that the impact of cancer susceptibility from genotype is

CD133+CD24lo defines a 5-Fluorouracil-resistant colon cancer stem cell-like phenotype

Science.gov (United States)

Paschall, Amy V.; Yang, Dafeng; Lu, Chunwan; Redd, Priscilla S.; Choi, Jeong-Hyeon; Heaton, Christopher M.; Lee, Jeffrey R.; Nayak-Kapoor, Asha; Liu, Kebin

2016-01-01

The chemotherapeutic agent 5-Fluorouracil (5-FU) is the most commonly used drug for patients with advanced colon cancer. However, development of resistance to 5-FU is inevitable in almost all patients. The mechanism by which colon cancer develops 5-FU resistance is still unclear. One recently proposed theory is that cancer stem-like cells underlie colon cancer 5-FU resistance, but the phenotypes of 5-FU-resistant colon cancer stem cells are still controversial. We report here that 5-FU treatment selectively enriches a subset of CD133+ colon cancer cells in vitro. 5-FU chemotherapy also increases CD133+ tumor cells in human colon cancer patients. However, sorted CD133+ colon cancer cells exhibit no increased resistance to 5-FU, and CD133 levels exhibit no correlation with colon cancer patient survival or cancer recurrence. Genome-wide analysis of gene expression between sorted CD133+ colon cancer cells and 5-FU-selected colon cancer cells identifies 207 differentially expressed genes. CD24 is one of the genes whose expression level is lower in the CD133+ and 5-FU-resistant colon cancer cells as compared to CD133+ and 5-FU-sensitive colon cancer cells. Consequently, CD133+CD24lo cells exhibit decreased sensitivity to 5-FU. Therefore, we determine that CD133+CD24lo phenotype defines 5-FU-resistant human colon cancer stem cell-like cells. PMID:27659530

Inhibition of autophagy induced by TSA sensitizes colon cancer cell to radiation.

Science.gov (United States)

He, Gang; Wang, Yan; Pang, Xueli; Zhang, Bo

2014-02-01

Radiotherapy is one of the main treatments for clinical cancer therapy. However, its application was limited due to lack of radiosensitivity in some cancers. Trichostatin A (TSA) is a classic histone deacetylases inhibitor (HDACi) that specifically inhibits the biochemical functions of HDAC and is demonstrated to be an active anticancer drug. However, whether it could sensitize colon cancer to radiation is not clear. Our results showed that TSA enhanced the radiosensitivity of colon cancer cells as determined by CCK-8 and clonogenic survival assay. Moreover, apoptotic cell death induced by radiation was enhanced by TSA treatment. Additionally, TSA also induced autophagic response in colon cancer cells, while autophagy inhibition led to cell apoptosis and enhanced the radiosensitivity of colon cancer cells. Our data suggested that inhibition of cytoprotective autophagy sensitizes cancer cell to radiation, which might be further investigated for clinical cancer radiotherapy.

Stage III & IV colon and rectal cancers share a similar genetic profile: a review of the Oregon Colorectal Cancer Registry.

Science.gov (United States)

Gawlick, Ute; Lu, Kim C; Douthit, Miriam A; Diggs, Brian S; Schuff, Kathryn G; Herzig, Daniel O; Tsikitis, Vassiliki L

2013-05-01

Determining the molecular profile of colon and rectal cancers offers the possibility of personalized cancer treatment. The purpose of this study was to determine whether known genetic mutations associated with colorectal carcinogenesis differ between colon and rectal cancers and whether they are associated with survival. The Oregon Colorectal Cancer Registry is a prospectively maintained, institutional review board-approved tissue repository with associated demographic and clinical information. The registry was queried for any patient with molecular analysis paired with clinical data. Patient demographics, tumor characteristics, microsatellite instability status, and mutational analysis for p53, AKT, BRAF, KRAS, MET, NRAS, and PIK3CA were analyzed. Categorical variables were compared using chi-square tests. Continuous variables between groups were analyzed using Mann-Whitney U tests. Kaplan-Meier analysis was used for survival studies. Comparisons of survival were made using log-rank tests. The registry included 370 patients: 69% with colon cancer and 31% with rectal cancer. Eighty percent of colon cancers and 68% of rectal cancers were stages III and IV. Mutational analysis found no significant differences in detected mutations between colon and rectal cancers, except that there were significantly more BRAF mutations in colon cancers compared with rectal cancers (10% vs 0%, P colon versus rectal cancers when stratified by the presence of KRAS, PIK3CA, and BRAF mutations. Stage III and IV colon and rectal cancers share similar molecular profiles, except that there were significantly more BRAF mutations in colon cancers compared with rectal cancers. Copyright © 2013 Elsevier Inc. All rights reserved.

Perioperative Colonic Evaluation in Patients with Rectal Cancer; MR Colonography Versus Standard Care

DEFF Research Database (Denmark)

Achiam, Michael Patrick; Løgager, Vibeke; Lund Rasmussen, Vera

2015-01-01

RATIONALE AND OBJECTIVES: Preoperative colonic evaluation is often inadequate because of cancer stenosis making a full conventional colonoscopy (CC) impossible. In several studies, cancer stenosis has been shown in up to 16%-34% of patients with colorectal cancer. The purpose of this study...... was to prospectively evaluate the completion rate of preoperative colonic evaluation and the quality of perioperative colonic evaluation using magnetic resonance colonography (MRC) in patients with rectal cancer. MATERIALS AND METHODS: Patients diagnosed with rectal cancer were randomized to either group A: standard...... preoperative diagnostic work-up or group B: preoperative MR diagnostic work-up (standard preoperative diagnostic work-up + MRC). A complete and adequate perioperative clean-colon evaluation (PCE) was defined as either a complete preoperative colonic evaluation or a complete colonic evaluation within 3 months...

OpenMSI Arrayed Analysis Toolkit: Analyzing Spatially Defined Samples Using Mass Spectrometry Imaging

DEFF Research Database (Denmark)

de Raad, Markus; de Rond, Tristan; Rübel, Oliver

2017-01-01

://openmsinersc.gov), a platform for storing, sharing, and analyzing MSI data. By using a web-based python notebook (Jupyter), OMAAT is accessible to anyone without programming experience yet allows experienced users to leverage all features. OMAAT was :evaluated by analyzing an MSI data set of a high-throughput glycoside...... processing tools for the analysis of large arrayed MSI sample sets. The OpenMSI Arrayed Analysis Toolkit (OMAAT) is a software package that addresses the challenges of analyzing spatially defined samples in MSI data sets. OMAAT is written in Python and is integrated with OpenMSI (http...

Pancreatoduodenectomy with colon resection for cancer: A nationwide retrospective analysis

NARCIS (Netherlands)

Marsman, E. Madelief; de Rooij, Thijs; van Eijck, Casper H.; Boerma, Djamila; Bonsing, Bert A.; van Dam, Ronald M.; van Dieren, Susan; Erdmann, Joris I.; Gerhards, Michael F.; de Hingh, Ignace H.; Kazemier, Geert; Klaase, Joost; Molenaar, I. Quintus; Patijn, Gijs A.; Scheepers, Joris J.; Tanis, Pieter J.; Busch, Olivier R.; Besselink, Marc G.

2016-01-01

Microscopically radical (R0) resection of pancreatic, periampullary, or colon cancer may occasionally require a pancreatoduodenectomy with colon resection (PD-colon), but the benefits of this procedure have been disputed, and multicenter studies on morbidity and oncologic outcomes after PD-colon are

File list: InP.Dig.50.AllAg.Colon_cancer [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available InP.Dig.50.AllAg.Colon_cancer hg19 Input control Digestive tract Colon cancer SRX12...155774,SRX124693,SRX124698 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Dig.50.AllAg.Colon_cancer.bed ...

File list: InP.Dig.20.AllAg.Colon_cancer [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available InP.Dig.20.AllAg.Colon_cancer hg19 Input control Digestive tract Colon cancer SRX12...124693,SRX124697,SRX124698 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Dig.20.AllAg.Colon_cancer.bed ...

File list: InP.Dig.10.AllAg.Colon_cancer [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available InP.Dig.10.AllAg.Colon_cancer hg19 Input control Digestive tract Colon cancer SRX12...155774,SRX625671,SRX155777 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Dig.10.AllAg.Colon_cancer.bed ...

File list: InP.Dig.05.AllAg.Colon_cancer [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available InP.Dig.05.AllAg.Colon_cancer hg19 Input control Digestive tract Colon cancer SRX12...124693,SRX124695,SRX124694 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Dig.05.AllAg.Colon_cancer.bed ...

Predicting opportunities to increase utilization of laparoscopy for colon cancer.

Science.gov (United States)

Keller, Deborah S; Parikh, Niraj; Senagore, Anthony J

2017-04-01

Despite proven safety and efficacy, rates of minimally invasive approaches for colon cancer remain low in the USA. Given the known benefits, investigating the root causes of underutilization and methods to increase laparoscopy is warranted. Our goal was to develop a predictive model of factors impacting use of laparoscopic surgery for colon cancer. The Premier Hospital Database was reviewed for elective colorectal resections for colon cancer (2009-2014). Patients were identified by ICD-9-CM diagnosis code and then stratified into open or laparoscopic approaches by ICD-9-CM procedure codes. An adjusted multivariate logistic regression model identified variables predictive of use of laparoscopy for colon cancer. A total of 24,245 patients were included-12,523 (52 %) laparoscopic and 11,722 (48 %) open. General surgeons performed the majority of all procedures (77.99 % open, 71.60 % laparoscopic). Overall use of laparoscopy increased from 48.94 to 52.03 % over the study period (p colon cancer laparoscopically. Colorectal surgeons were 32 % more likely to approach a case laparoscopically than general surgeons (OR 1.315, 95 % CI [1.222, 1.415], p characteristics that can be identified preoperatively to predict who will undergo surgery for colon cancer using laparoscopy. However, additional patients may be eligible for laparoscopy based on patient-level characteristics. These results have implications for regionalization and increasing teaching of MIS. Recognizing and addressing these variables with training and recruiting could increase use of minimally invasive approaches, with the associated clinical and financial benefits.

Ursodeoxycholic acid inhibits the proliferation of colon cancer cells by regulating oxidative stress and cancer stem-like cell growth

Science.gov (United States)

Kim, EuiJoo

2017-01-01

Introduction The regulation of reactive oxygen species (ROS) exists as a therapeutic target for cancer treatments. Previous studies have shown that ursodeoxycholic acid (UDCA) suppresses the proliferation of colon cancer cells. The aim of this study was to evaluate the effect of UDCA upon the proliferation of colon cancer cells as a direct result of the regulation of ROS. Method Colon cancer cell lines (HT29 and HCT116) were treated with UDCA. The total number of cells and the number of dead cells were determined using cell counters. A fluorescein isothiocyanate-bromodeoxyuridine flow kit was used to analyze cell cycle variations. Upon exposure to UDCA, the protein levels of p27, p21, CDK2, CDK4 and CDK6 were determined using western blotting, and qRT-PCR was used to determine levels of mRNA. We preformed dichlorofluorescindiacetate (DCF-DA) staining to detect alteration of intracellular ROS using fluorescence activated cell sorting (FACS). Colon cancer stem-like cell lines were generated by tumorsphere culture and treated with UDCA for seven days. The total number of tumorspheres was determined using microscopy. Results We found that UDCA reduced the total number of colon cancer cells, but did not increase the number of dead cells. UDCA inhibited the G1/S and G2/M transition phases in colon cancer cells. UDCA induced expression of cell cycle inhibitors such as p27 and p21. However, it was determined that UDCA suppressed levels of CDK2, CDK4, and CDK6. UDCA regulated intracellular ROS generation in colon cancer cells, and induced activation of Erk1/2. Finally, UDCA inhibited formation of colon cancer stem-like cells. Conclusion Our results indicate that UDCA suppresses proliferation through regulation of oxidative stress in colon cancer cells, as well as colon cancer stem-like cells. PMID:28708871

Up-regulation of CNDP2 facilitates the proliferation of colon cancer

OpenAIRE

Xue, Conglong; Zhang, Zhenwei; Yu, Honglan; Yu, Miao; Yuan, Kaitao; Yang, Ting; Miao, Mingyong; Shi, Hanping

2014-01-01

Background Cytosolic nonspecific dipetidase (CN2) belongs to the family of M20 metallopeptidases. It was stated in previous articles that higher expression levels of CN2 were observed in renal cell carcinoma and breast cancer. Our study explored the correlation between CN2 and colon carcinogenesis. Methods We analysed the relationship between 183 patients clinicopathological characteristics and its CN2 expression. To detect the levels of CN2 in colon cancer cell lines and colon cancer tissues...

Noscapine induces mitochondria-mediated apoptosis in human colon cancer cells in vivo and in vitro

Energy Technology Data Exchange (ETDEWEB)

Yang, Zi-Rong; Liu, Meng; Peng, Xiu-Lan; Lei, Xiao-Fei; Zhang, Ji-Xiang [Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province (China); Dong, Wei-Guo, E-mail: dongwg1966@yahoo.com.cn [Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province (China)

2012-05-11

Highlights: Black-Right-Pointing-Pointer Noscapine inhibited cell viability of colon cancer in a time- and dose- dependent manner. Black-Right-Pointing-Pointer G{sub 2}/M phase arrest and chromatin condensation and nuclear fragmentation were induced. Black-Right-Pointing-Pointer Noscapine promoted apoptosis via mitochondrial pathways. Black-Right-Pointing-Pointer Tumorigenicity was inhibited by noscapine. -- Abstract: Noscapine, a phthalide isoquinoline alkaloid derived from opium, has been widely used as a cough suppressant for decades. Noscapine has recently been shown to potentiate the anti-cancer effects of several therapies by inducing apoptosis in various malignant cells without any detectable toxicity in cells or tissues. However, the mechanism by which noscapine induces apoptosis in colon cancer cells remains unclear. The signaling pathways by which noscapine induces apoptosis were investigated in colon cancer cell lines treated with various noscapine concentrations for 72 h, and a dose-dependent inhibition of cell viability was observed. Noscapine effectively inhibited the proliferation of LoVo cells in vitro (IC{sub 50} = 75 {mu}M). This cytotoxicity was reflected by cell cycle arrest at G{sub 2}/M and subsequent apoptosis, as indicated by increased chromatin condensation and fragmentation, the upregulation of Bax and cytochrome c (Cyt-c), the downregulation of survivin and Bcl-2, and the activation of caspase-3 and caspase-9. Moreover, in a xenograft tumor model in mice, noscapine injection clearly inhibited tumor growth via the induction of apoptosis, which was demonstrated using a TUNEL assay. These results suggest that noscapine induces apoptosis in colon cancer cells via mitochondrial pathways. Noscapine may be a safe and effective chemotherapeutic agent for the treatment of human colon cancer.

[A Case of Performed Right Colectomy with Pancreato-Duodenectomy for Transverse Colon Cancer Invased to Duodenum].

Science.gov (United States)

Udo, Ryutaro; Enomoto, Masanobu; Tsurui, Kazushige; Kuboyama, Yuu; Kuwabara, Hiroshi; Shigoka, Masatoshi; Ishizaki, Tetsuo; Katsumata, Kenji; Obikane, Hiyo; Tsuchida, Akihiko

2018-04-01

There is a clear consensus regarding the combined resection of organs with cancer invasion, patients with colon cancer. However, there are very few reports to our knowledge regarding the use of pancreato-duodenectomy(PD)for colon cancer patients with cancer invasion in the duodenum. We here report a colon cancer patient in whom we performed PD and right hemicolectomy, who showed favorable results with no recurrence. The patient was a 69-year-old woman. Her chief complaint was hypogastric pain. Her previous doctor performed colonoscopy and a colonoscopic biopsy, and detected a type 2 lesion, throughout the entire circumference of the transverse colon near the liver, and she was diagnosed with adenocarcinoma. From further imaging analyses, she was diagnosed as having transverse colon cancer with invasion into the superior mesenteric vein(SMV), duodenum, and pancreatic head, and No. 223 lymph node metastasis. The patient's cancer was concluded to be unresectable, and she underwent chemotherapy, namely mFOLFOX6 with cetuxiumab(Cmab). One course of mFOLFOX with Cmab, the patient decided to consult our hospital for a second opinion. We concluded that her cancer was resectable, so we performed PD, right hemicolectomy, and resection and reconstruction of a part of the SMV. The operation time was 5 hours 17 minutes, and total blood loss was 190 mL. The histopathological diagnosis was tub2, T4b(duodenum and, tissue surrounding the SMV), int, INF b, ly1, v2, PN1b, EX(+)/ND(PN+, v+), PM0(25 cm), DM0(14.3 cm), N1(1/ 20), H0, P0, M0, pStage III a. She was discharged 15 days after surgery with no complications, and thereafter received ajduvant chemotherapy(capecitabine with oxaliplatin)as an outpatient. After 3 courses, capecitabine with oxaliplatin was changed to capecitabine because she developed a nervous system disorder, and she was further treated for approximately about 6 months. She is doing well at the time of writing, with no recurrences for 2 years. We suggest that PD

Understanding your colon cancer risk

Science.gov (United States)

... for women and 2 drinks per day for men DO NOT smoke You can also have genetic testing done to assess your risk for colon cancer. If you have a strong family history of the disease, talk with your ...

[The trends in clinical characteristics of colon cancer in last two decades].

Science.gov (United States)

Li, Jing-nan; Zhao, Li; Zheng, Wei-yang; Miao, Zheng; Tang, Xiao-yan; Qian, Jia-ming

2010-03-01

To explore the changing of clinical features of colon cancer within 20 years, in order to help early diagnosis and screening of colon cancer in China. A total of 1233 cases of colon cancer in Peking Union Medical College Hospital during 1989 - 2008 were retrospectively studied. All patients were divided into two groups according to the date of onset (1989 - 1998 and 1999 - 2008), the demographic features, clinical manifestations, laboratory examination, colonoscopy characteristics and pathological stage were analyzed. Comparing with 1989 - 1998, in recently 10 years, the morbidity of colon cancer increased, more female and old patients appeared; hematochezia significant less (51.8% vs 31.7%, P colon in 1989 - 1998 (44.6%) shift to sigmoid colon (38.7%) and descending colon (22.7%) up to now. Operation was the first choice of treatment, the early stage (Duke A) patients significant increased (9.3% vs 23.8%, P colon cancer obviously increased, the age was become elder and female patients were increased. The clinical manifestation became more nonspecific. According with the improvement of stool occult blood, serum CEA and colonoscopy detective method and wild spread using, more and more early stage patients were diagnosed. The location of tumor shift from right side to left side, and coincidence with west countries gradually.

Cancer care coordinators in stage III colon cancer: a cost-utility analysis.

Science.gov (United States)

Blakely, Tony; Collinson, Lucie; Kvizhinadze, Giorgi; Nair, Nisha; Foster, Rachel; Dennett, Elizabeth; Sarfati, Diana

2015-08-05

There is momentum internationally to improve coordination of complex care pathways. Robust evaluations of such interventions are scarce. This paper evaluates the cost-utility of cancer care coordinators for stage III colon cancer patients, who generally require surgery followed by chemotherapy. We compared a hospital-based nurse cancer care coordinator (CCC) with 'business-as-usual' (no dedicated coordination service) in stage III colon cancer patients in New Zealand. A discrete event microsimulation model was constructed to estimate quality-adjusted life-years (QALYs) and costs from a health system perspective. We used New Zealand data on colon cancer incidence, survival, and mortality as baseline input parameters for the model. We specified intervention input parameters using available literature and expert estimates. For example, that a CCC would improve the coverage of chemotherapy by 33% (ranging from 9 to 65%), reduce the time to surgery by 20% (3 to 48%), reduce the time to chemotherapy by 20% (3 to 48%), and reduce patient anxiety (reduction in disability weight of 33%, ranging from 0 to 55%). Much of the direct cost of a nurse CCC was balanced by savings in business-as-usual care coordination. Much of the health gain was through increased coverage of chemotherapy with a CCC (especially older patients), and reduced time to chemotherapy. Compared to 'business-as-usual', the cost per QALY of the CCC programme was $NZ 18,900 (≈ $US 15,600; 95% UI: $NZ 13,400 to 24,600). By age, the CCC intervention was more cost-effective for colon cancer patients costs, meaning the cost-effectiveness was roughly comparable between ethnic groups. Such a nurse-led CCC intervention in New Zealand has acceptable cost-effectiveness for stage III colon cancer, meaning it probably merits funding. Each CCC programme will differ in its likely health gains and costs, making generalisation from this evaluation to other CCC interventions difficult. However, this evaluation suggests

Green vegetables and colon cancer: the mechanism of a protective effect by chlorophyll

NARCIS (Netherlands)

Vogel, de J.

2006-01-01

One of the important environmental determinants of the risk of colon cancer is the composition of the diet. Regular consumption of high amounts of red meat increases colon cancer risk. In contrast, consumption of green vegetables decreases the risk of colon cancer. This thesis provides a molecular

BG-4, a novel anticancer peptide from bitter gourd (Momordica charantia), promotes apoptosis in human colon cancer cells.

Science.gov (United States)

Dia, Vermont P; Krishnan, Hari B

2016-09-15

Momordica charantia is a perennial plant with reported health benefits. BG-4, a novel peptide from Momordica charantia, was isolated, purified and characterized. The trypsin inhibitory activity of BG-4 is 8.6 times higher than purified soybean trypsin inhibitor. The high trypsin inhibitory activity of BG-4 may be responsible for its capability to cause cytotoxicity to HCT-116 and HT-29 human colon cancer cells with ED50 values of 134.4 and 217.0 μg/mL after 48 h of treatment, respectively. The mechanism involved in the cytotoxic effect may be associated with induction of apoptosis as evidenced by increased percentage of HCT-116 and HT-29 colon cancer cells undergoing apoptosis from 5.4% (untreated) to 24.8% (BG-4 treated, 125 μg/mL for 16 h) and 8.5% (untreated) to 31.9% (BG-4 treated, 125 μg/mL for 16 h), respectively. The molecular mechanistic explanation in the apoptosis inducing property of BG-4 is due to reduced expression of Bcl-2 and increased expression of Bax leading to increased expression of caspase-3 and affecting the expression of cell cycle proteins p21 and CDK2. This is the first report on the anti-cancer potential of a novel bioactive peptide isolated from Momordica charantia in vitro supporting the potential therapeutic property of BG-4 against colon cancer that must be addressed using in vivo models of colon carcinogenesis.

Analysis on misdiagnosed cases of right colon cancer as appendicitis

Directory of Open Access Journals (Sweden)

Sijia Liu

2016-08-01

Full Text Available The aim of this case report is to investigate the causes of misdiagnosing right colon cancer as appendicitis, in order to reduce the misdiagnosis rate. The process of diagnosing and treating 44 misdiagnosed right colon cancer cases was analyzed. It was found that the right colonic lumen in these patients was thick, and their cancer consisted mostly of the ulcerative type or of a cauliflower-like tumor that protruded into the intestinal cavity. Moreover, ring-shaped and structured cancer was rarely observed, which suggested a decreased likelihood of obstruction. The patients showed limited peritoneal irritation signs in their right lower abdomen, which was also a potential cause for misdiagnosis. Right colon cancer associated with appendicitis is easily misdiagnosed as simple appendicitis, chronic appendicitis, or appendiceal abscess. Therefore, it is necessary to raise general awareness on the manifestations of the disease in order to exclude other common complications during diagnosis and to reduce the misdiagnosis rate. An accurate early diagnosis and treatment will improve patient prognosis.

Overexpression of Long Non-Coding RNA TUG1 Promotes Colon Cancer Progression

OpenAIRE

Zhai, Hui-yuan; Sui, Ming-hua; Yu, Xiao; Qu, Zhen; Hu, Jin-chen; Sun, Hai-qing; Zheng, Hai-tao; Zhou, Kai; Jiang, Li-xin

2016-01-01

Background Colon cancer is one of the most prevalent and deadly cancers worldwide. It is still necessary to further define the mechanisms and explore therapeutic targets of colon cancer. Dysregulation of long noncoding RNAs (lncRNAs) has been shown to be correlated with diverse biological processes, including tumorigenesis. This study aimed to characterize the biological mechanism of taurine-upregulated gene 1 (TUG1) in colon cancer. Material/Methods qRT-PCR was used to analyze the expression...

Deblurring sequential ocular images from multi-spectral imaging (MSI) via mutual information.

Science.gov (United States)

Lian, Jian; Zheng, Yuanjie; Jiao, Wanzhen; Yan, Fang; Zhao, Bojun

2018-06-01

Multi-spectral imaging (MSI) produces a sequence of spectral images to capture the inner structure of different species, which was recently introduced into ocular disease diagnosis. However, the quality of MSI images can be significantly degraded by motion blur caused by the inevitable saccades and exposure time required for maintaining a sufficiently high signal-to-noise ratio. This degradation may confuse an ophthalmologist, reduce the examination quality, or defeat various image analysis algorithms. We propose an early work specially on deblurring sequential MSI images, which is distinguished from many of the current image deblurring techniques by resolving the blur kernel simultaneously for all the images in an MSI sequence. It is accomplished by incorporating several a priori constraints including the sharpness of the latent clear image, the spatial and temporal smoothness of the blur kernel and the similarity between temporally-neighboring images in MSI sequence. Specifically, we model the similarity between MSI images with mutual information considering the different wavelengths used for capturing different images in MSI sequence. The optimization of the proposed approach is based on a multi-scale framework and stepwise optimization strategy. Experimental results from 22 MSI sequences validate that our approach outperforms several state-of-the-art techniques in natural image deblurring.

Cancer of the colon spleen angle. Presentation of a case

International Nuclear Information System (INIS)

Martinez Sanchez, Yariana; De la Rosa Perez, Nereida; Barcelo Casanova, Renato E

2010-01-01

The colon cancer is currently an important public health problem in developed countries. It is the fourth most common cancer in the world. We report the case of a 65-years-old, black, female patient, assisting our consultation with dyspeptic disturbances as the unique symptom, without known risk factors. We indicated a colon by enema and a distal narrowing was observed at the colon spleen angle, at the same zone of the physiologic narrowing at that level. A colonoscopy was carried out diagnosing a left colon tumor near the spleen angle. It was operated with segmental resection of the spleen angle and a biopsy was made. Pathologic anatomy informed a well-differentiated colon adenocarcinoma

Review article: loss of the calcium-sensing receptor in colonic epithelium is a key event in the pathogenesis of colon cancer.

LENUS (Irish Health Repository)

Rogers, Ailín C

2012-03-01

The calcium-sensing receptor (CaSR) is expressed abundantly in normal colonic epithelium and lost in colon cancer, but its exact role on a molecular level and within the carcinogenesis pathway is yet to be described. Epidemiologic studies show that inadequate dietary calcium predisposes to colon cancer; this may be due to the ability of calcium to bind and upregulate the CaSR. Loss of CaSR expression does not seem to be an early event in carcinogenesis; indeed it is associated with late stage, poorly differentiated, chemo-resistant tumors. Induction of CaSR expression in neoplastic colonocytes arrests tumor progression and deems tumors more sensitive to chemotherapy; hence CaSR may be an important target in colon cancer treatment. The CaSR has a complex role in colon cancer; however, more investigation is required on a molecular level to clarify its exact function in carcinogenesis. This review describes the mechanisms by which the CaSR is currently implicated in colon cancer and identifies areas where further study is needed.

Comparison of oncological outcomes of right-sided colon cancer versus left-sided colon cancer after curative resection: Which side is better outcome?

Science.gov (United States)

Lim, Dae Ro; Kuk, Jung Kul; Kim, Taehyung; Shin, Eung Jin

2017-10-01

There are embryological origins, anatomical, histological, genetic, and immunological differences between right-sided colon cancer (RCC) and left-sided colon cancer (LCC). Many studies have sought to determine the survival and prognosis according to tumor location. This study aimed to analyze outcomes between RCC and LCC. Between January 2000 and December 2012, data on 414 patients who underwent curative resection for RCC and LCC were retrieved from a retrospective database. Propensity score matching (1:1) was performed and RCC was identified in 207 and LCC in 207 patients. On average, RCC exhibited a more advanced N stage, increased tumor size, more frequently poorly differentiated tumors, more harvested lymph nodes, and more positivity of lymphovascular invasion than LCC. With a median follow-up of 66.7 months, the 5-year overall survival (OS) rates for RCC and LCC were 82.1% and 88.7%, respectively, (P cancers, the DFS rates were 61.1% (RCC) and 81.9% (LCC; P colon cancer is needed.

A comparison of 12-gene colon cancer assay gene expression in African American and Caucasian patients with stage II colon cancer.

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Govindarajan, Rangaswamy; Posey, James; Chao, Calvin Y; Lu, Ruixiao; Jadhav, Trafina; Javed, Ahmed Y; Javed, Awais; Mahmoud, Fade A; Osarogiagbon, Raymond U; Manne, Upender

2016-06-18

African American (AA) colon cancer patients have a worse prognosis than Caucasian (CA) colon cancer patients, however, reasons for this disparity are not well understood. To determine if tumor biology might contribute to differential prognosis, we measured recurrence risk and gene expression using the Oncotype DX® Colon Cancer Assay (12-gene assay) and compared the Recurrence Score results and gene expression profiles between AA patients and CA patients with stage II colon cancer. We retrieved demographic, clinical, and archived tumor tissues from stage II colon cancer patients at four institutions. The 12-gene assay and mismatch repair (MMR) status were performed by Genomic Health (Redwood City, California). Student's t-test and the Wilcoxon rank sum test were used to compare Recurrence Score data and gene expression data from AA and CA patients (SAS Enterprise Guide 5.1). Samples from 122 AA and 122 CA patients were analyzed. There were 118 women (63 AA, 55 CA) and 126 men (59 AA, 67 CA). Median age was 66 years for AA patients and 68 for CA patients. Age, gender, year of surgery, pathologic T-stage, tumor location, the number of lymph nodes examined, lymphovascular invasion, and MMR status were not significantly different between groups (p = 0.93). The mean Recurrence Score result for AA patients (27.9 ± 12.8) and CA patients (28.1 ± 11.8) was not significantly different and the proportions of patients with high Recurrence Score values (≥41) were similar between the groups (17/122 AA; 15/122 CA). None of the gene expression variables, either single genes or gene groups (cell cycle group, stromal group, BGN1, FAP, INHBA1, Ki67, MYBL2, cMYC and GADD45B), was significantly different between the racial groups. After controlling for clinical and pathologic covariates, the means and distributions of Recurrence Score results and gene expression profiles showed no statistically significant difference between patient groups. The distribution of

A comparison of 12-gene colon cancer assay gene expression in African American and Caucasian patients with stage II colon cancer

International Nuclear Information System (INIS)

Govindarajan, Rangaswamy; Posey, James; Chao, Calvin Y.; Lu, Ruixiao; Jadhav, Trafina; Javed, Ahmed Y.; Javed, Awais; Mahmoud, Fade A.; Osarogiagbon, Raymond University; Manne, Upender

2016-01-01

African American (AA) colon cancer patients have a worse prognosis than Caucasian (CA) colon cancer patients, however, reasons for this disparity are not well understood. To determine if tumor biology might contribute to differential prognosis, we measured recurrence risk and gene expression using the Oncotype DX® Colon Cancer Assay (12-gene assay) and compared the Recurrence Score results and gene expression profiles between AA patients and CA patients with stage II colon cancer. We retrieved demographic, clinical, and archived tumor tissues from stage II colon cancer patients at four institutions. The 12-gene assay and mismatch repair (MMR) status were performed by Genomic Health (Redwood City, California). Student’s t-test and the Wilcoxon rank sum test were used to compare Recurrence Score data and gene expression data from AA and CA patients (SAS Enterprise Guide 5.1). Samples from 122 AA and 122 CA patients were analyzed. There were 118 women (63 AA, 55 CA) and 126 men (59 AA, 67 CA). Median age was 66 years for AA patients and 68 for CA patients. Age, gender, year of surgery, pathologic T-stage, tumor location, the number of lymph nodes examined, lymphovascular invasion, and MMR status were not significantly different between groups (p = 0.93). The mean Recurrence Score result for AA patients (27.9 ± 12.8) and CA patients (28.1 ± 11.8) was not significantly different and the proportions of patients with high Recurrence Score values (≥41) were similar between the groups (17/122 AA; 15/122 CA). None of the gene expression variables, either single genes or gene groups (cell cycle group, stromal group, BGN1, FAP, INHBA1, Ki67, MYBL2, cMYC and GADD45B), was significantly different between the racial groups. After controlling for clinical and pathologic covariates, the means and distributions of Recurrence Score results and gene expression profiles showed no statistically significant difference between patient groups. The distribution of Recurrence Score

Incidence and mortality from colon and rectal cancer in Midwestern Brazil.

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Oliveira, Anderson Gomes de; Curado, Maria Paula; Koechlin, Alice; Oliveira, José Carlos de; Silva, Diego Rodrigues Mendonça E

2016-01-01

To describe the incidence and mortality rates from colon and rectal cancer in Midwestern Brazil. Data for the incidence rates were obtained from the Population-Based Cancer Registry (PBCR) according to the available period. Mortality data were obtained from the Mortality Information System (SIM) for the period between 1996 and 2008. Incidence and mortality rates were calculated by gender and age groups. Mortality trends were analyzed by the Joinpoint software. The age-period-cohort effects were calculated by the R software. The incidence rates for colon cancer vary from 4.49 to 23.19/100,000, while mortality rates vary from 2.85 to 14.54/100,000. For rectal cancer, the incidence rates range from 1.25 to 11.18/100,000 and mortality rates range between 0.30 and 7.90/100,000. Colon cancer mortality trends showed an increase among males in Cuiabá, Campo Grande, and Goiania. For those aged under 50 years, the increased rate was 13.2% in Campo Grande. For those aged over 50 years, there was a significant increase in the mortality in all capitals. In Goiânia, rectal cancer mortality in males increased 7.3%. For females below 50 years of age in the city of Brasilia, there was an increase of 8.7%, while females over 50 years of age in Cuiaba showed an increase of 10%. There is limited data available on the incidence of colon and rectal cancer for the Midwest region of Brazil. Colon cancer mortality has generally increased for both genders, but similar data were not verified for rectal cancer. The findings presented herein demonstrate the necessity for organized screening programs for colon and rectal cancer in Midwestern Brazil.

Locally advanced colon cancer with cutaneous invasion: case report.

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Tenreiro, Nádia; Ferreira, Cátia; Silva, Silvia; Marques, Rita; Ribeiro, Artur; Sousa, Paulo Jorge; Luís, Fernando Próspero

2017-03-01

Locally advanced colon cancer with direct abdominal wall and skin invasion is an extremely rare finding with most data being derived from case reports, historical autopsy-based or single-center retrospective studies. We present a unique case of a colon cancer with direct cutaneous invasion and colocutaneous fistulization. Eighty-six year old Caucasian female with multiple comorbidities, referred to Surgical Consultation due to ulcerated skin lesion in the abdomen. She had a long-standing large umbilical hernia but with no previous episodes of incarceration or occlusive symptoms. She denied any digestive or constitutional symptoms. Physical examination showed a large non-reducible umbilical hernia, with an associated painless firm mass within the hernia sac and cutaneous ulcerated growth. Colonoscopy revealed transverse colon cancer (endoscopic biopsy of the tumor and skin punch biopsy confirmed adenocarcinoma of the colon). Computed tomography showed a tumoral mass within the umbilical hernia, with cutaneous infiltration and enlarged regional lymph nodes. Rapid local progression led to colocutaneous fistula with total fecal diversion. We performed an extended right hemicolectomy with en bloc excision of the hernia sac and infiltrating cutaneous mass. In the current era of widespread use of screening colonoscopies, initial diagnosis of locally advanced colon cancer is decreasing. However, this unique case presented an opportunity to recall the advantages of multivisceral resections.

Advanced colonic cancer associated with radiation colitis, report of a case

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Moriyama, Tomohiko; Sato, Tomoo; Iwai, Keiichirou; Yao, Takashi; Mibu, Ryuichi; Iida, Mitsuo [Kyushu Univ., Fukuoka (Japan). Graduate School of Medical Sciences; Matsumoto, Takayuki [Kyushu Univ., Fukuoka (Japan). Hospital

2002-07-01

A 68-year-old woman with a history of irradiation for uterine cervical cancer was admitted to our institute, because of abdominal distension. Barium enema examination and total colonoscopy revealed narrowing, irregular mucosa and an ulcerating tumor in the sigmoid colon and a flat elevation in the transverse colon. Biopsy specimens from these tumors contained adenocarcinoma. Histological examination of the resected colon revealed the tumor in the sigmoid colon to be a well-differentiated adenocarcinoma invading the subserosa and that in the transverse colon to be an intramucosal adenocarcinoma. There were also areas of low or high grade dysplasia in the sigmoid colon. Histological findings compatible with radiation colitis were found in the sigmoid colon. These clinicopathologic features suggested a diagnosis of colonic cancer associated with radiation colitis. (author)

Advanced colonic cancer associated with radiation colitis, report of a case

International Nuclear Information System (INIS)

Moriyama, Tomohiko; Sato, Tomoo; Iwai, Keiichirou; Yao, Takashi; Mibu, Ryuichi; Iida, Mitsuo; Matsumoto, Takayuki

2002-01-01

A 68-year-old woman with a history of irradiation for uterine cervical cancer was admitted to our institute, because of abdominal distension. Barium enema examination and total colonoscopy revealed narrowing, irregular mucosa and an ulcerating tumor in the sigmoid colon and a flat elevation in the transverse colon. Biopsy specimens from these tumors contained adenocarcinoma. Histological examination of the resected colon revealed the tumor in the sigmoid colon to be a well-differentiated adenocarcinoma invading the subserosa and that in the transverse colon to be an intramucosal adenocarcinoma. There were also areas of low or high grade dysplasia in the sigmoid colon. Histological findings compatible with radiation colitis were found in the sigmoid colon. These clinicopathologic features suggested a diagnosis of colonic cancer associated with radiation colitis. (author)

Reproductive and hormonal factors in male and female colon cancer

NARCIS (Netherlands)

Kampman, E.; Bijl, A.J.; Kok, C.; Veer, P. van 't

1994-01-01

We analysed data from a case-control study in the Netherlands in order to investigate whether reproductive events and hormonal factors are similarly related to colon cancer risk in men and women after adjustment for dietary factors. In total, 232 colon cancer cases (102 women, 130 men) and 259

Prognostic and predictive potential molecular biomarkers in colon cancer.

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Nastase, A; Pâslaru, L; Niculescu, A M; Ionescu, M; Dumitraşcu, T; Herlea, V; Dima, S; Gheorghe, C; Lazar, V; Popescu, I

2011-01-01

An important objective in nowadays research is the discovery of new biomarkers that can detect colon tumours in early stages and indicate with accuracy the status of the disease. The aim of our study was to identify potential biomarkers for colon cancer onset and progression. We assessed gene expression profiles of a list of 10 candidate genes (MMP-1, MMP-3, MMP-7, DEFA 1, DEFA-5, DEFA-6, IL-8, CXCL-1, SPP-1, CTHRC-1) by quantitative real time PCR in triplets of colonic mucosa (normal, adenoma, tumoral tissue) collected from the same patient during surgery for a group of 20 patients. Additionally we performed immunohistochemistry for DEFA1-3 and SPP1. We remarked that DEFA5 and DEFA6 are key factors in adenoma formation (p<0.05). MMP7 is important in the transition from a benign to a malignant status (p <0.01) and further in metastasis being a prognostic indicator for tumor transformation and for the metastatic potential of cancer cells. IL8, irrespective of tumor stage, has a high mRNA level in adenocarcinoma (p< 0.05). The level of expression for SPP1 is correlated with tumor level. We suggest that high levels of DEFAS, DEFA6 (key elements in adenoma formation), MMP7 (marker of colon cancer onset and progression to metastasis), SPP1 (marker of progression) and IL8 could be used to diagnose an early stage colon cancer and to evaluate the prognostic of progression for colon tumors. Further, if DEFA5 and DEFA6 level of expression are low but MMP7, SPP1 and IL8 level are high we could point out that the transition from adenoma to adenocarcinoma had already occurred. Thus, DEFA5, DEFA6, MMP7, IL8 and SPP1 consist in a valuable panel of biomarkers, whose detection can be used in early detection and progressive disease and also in prognostic of colon cancer.

Colon cancer and the consumption of red and processed meat: an ...

African Journals Online (AJOL)

Colon cancer and the consumption of red and processed meat: an association that is medium, rare or well done? ... South African Journal of Clinical Nutrition ... In 2015, the International Agency for Research on Cancer (IARC) indicated that red meat is a probable cause of colon cancer, while processed meat was classified ...

Induction of cancer stem cell properties in colon cancer cells by defined factors.

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Nobu Oshima

Full Text Available Cancer stem cells (CSCs are considered to be responsible for the dismal prognosis of cancer patients. However, little is known about the molecular mechanisms underlying the acquisition and maintenance of CSC properties in cancer cells because of their rarity in clinical samples. We herein induced CSC properties in cancer cells using defined factors. We retrovirally introduced a set of defined factors (OCT3/4, SOX2 and KLF4 into human colon cancer cells, followed by culture with conventional serum-containing medium, not human embryonic stem cell medium. We then evaluated the CSC properties in the cells. The colon cancer cells transduced with the three factors showed significantly enhanced CSC properties in terms of the marker gene expression, sphere formation, chemoresistance and tumorigenicity. We designated the cells with CSC properties induced by the factors, a subset of the transduced cells, as induced CSCs (iCSCs. Moreover, we established a novel technology to isolate and collect the iCSCs based on the differences in the degree of the dye-effluxing activity enhancement. The xenografts derived from our iCSCs were not teratomas. Notably, in contrast to the tumors from the parental cancer cells, the iCSC-based tumors mimicked actual human colon cancer tissues in terms of their immunohistological findings, which showed colonic lineage differentiation. In addition, we confirmed that the phenotypes of our iCSCs were reproducible in serial transplantation experiments. By introducing defined factors, we generated iCSCs with lineage specificity directly from cancer cells, not via an induced pluripotent stem cell state. The novel method enables us to obtain abundant materials of CSCs that not only have enhanced tumorigenicity, but also the ability to differentiate to recapitulate a specific type of cancer tissues. Our method can be of great value to fully understand CSCs and develop new therapies targeting CSCs.

IL33 Promotes Colon Cancer Cell Stemness via JNK Activation and Macrophage Recruitment

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Fang, Min; Li, Yongkui; Huang, Kai; Qi, Shanshan; Zhang, Jian; Zgodzinski, Witold; Majewski, Marek; Wallner, Grzegorz; Gozdz, Stanislaw; Macek, Pawel; Kowalik, Artur; Pasiarski, Marcin; Grywalska, Ewelina; Vatan, Linda; Nagarsheth, Nisha; Li, Wei; Zhao, Lili; Kryczek, Ilona; Wang, Guobin; Wang, Zheng; Zou, Weiping; Wang, Lin

2018-01-01

The expression and biological role of IL33 in colon cancer is poorly understood. In this study, we show that IL33 is expressed by vascular endothelial cells and tumor cells in the human colon cancer microenvironment. Administration of human IL33 and overexpression of murine IL33 enhanced human and murine colon cancer cell growth in vivo, respectively. IL33 stimulated cell sphere formation and prevented chemotherapy-induced tumor apoptosis. Mechanistically, IL33 activated core stem cell genes NANOG, NOTCH3, and OCT3/4 via the ST2 signaling pathway, and induced phosphorylation of c-Jun N terminal kinase (JNK) activation and enhanced binding of c-Jun to the promoters of the core stem cell genes. Moreover, IL33 recruited macrophages into the cancer microenvironment and stimulated them to produce prostaglandin E2, which supported colon cancer stemness and tumor growth. Clinically, tumor IL33 expression associated with poor survival in patients with metastatic colon cancer. Thus, IL33 dually targets tumor cells and macrophages and endows stem-like qualities to colon cancer cells to promote carcinogenesis. Collectively, our work reveals an immune-associated mechanism that extrinsically confers cancer cell stemness properties. Targeting the IL33 signaling pathway may offer an opportunity to treat patients with metastatic cancer. PMID:28249897

[Comparison of clinicopathological features and prognosis between left-sided colon cancer and right-sided colon cancer].

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Gao, Xianhua; Yu, Guanyu; Liu, Peng; Hao, Liqiang; Liu, Lianjie; Zhang, Wei

2017-06-25

To compare the clinicopathological features and prognosis between left-sided colon cancer (LC) and right-sided colon cancer (RC). Clinicopathological and follow-up data of 2 174 colon carcinoma cases undergoing resection at Shanghai Changhai Hospital of The Second Military Medical University from January 2000 to December 2010 were retrospectively analyzed. Patients with transverse colon cancer, overlapping position, unknown location, recurrent cancer, multiple primary cancer, concomitant malignant tumors, preoperative chemotherapy, local resection, incomplete clinical data and missed follow up were excluded. Finally, a total of 1 036 patients, whose primary tumors were radically removed, were enrolled, with 563 patients in LC group (including carcinoma in cecum, ascending colon and hepatic flexure) and 473 in RC group (including carcinoma in splenic flexure, descending colon and sigmoid colon). The clinicopathological features and survival, including median overall survival, 5-year overall survival rate, tumor specific median overall survival, cancer specific 5-year overall survival rate, were compared between LC and RC groups. Tumor specific overall survival was defined as the period between operation date to the date of death caused by cancer progression. Multivariate Cox regression analysis was used to analyze the influencing factors of survival. Propensity score matching was carried out to balance the clinicopathological factors between the two groups with the SAS 9.3, taking the following parameters into consideration (age, gender, gross appearance, tumor diameter, invasion depth, lymph node metastasis, distant metastasis, TNM stages, differentiation, CEA and CA199-9). Patients in RC group and LC group were matched according to the propensity scores and the clinicopathological characteristics and prognosis of two groups were compared again. No significant differences were identified between the two groups in age, distant metastasis and serum CEA level

Inactivation of Adenomatous Polyposis Coli Reduces Bile Acid/Farnesoid X Receptor Expression through Fxr gene CpG Methylation in Mouse Colon Tumors and Human Colon Cancer Cells.

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Selmin, Ornella I; Fang, Changming; Lyon, Adam M; Doetschman, Tom C; Thompson, Patricia A; Martinez, Jesse D; Smith, Jeffrey W; Lance, Peter M; Romagnolo, Donato F

2016-02-01

The farnesoid X receptor (FXR) regulates bile acid (BA) metabolism and possesses tumor suppressor functions. FXR expression is reduced in colorectal tumors of subjects carrying inactivated adenomatous polyposis coli (APC). Identifying the mechanisms responsible for this reduction may offer new molecular targets for colon cancer prevention. We investigated how APC inactivation influences the regulation of FXR expression in colonic mucosal cells. We hypothesized that APC inactivation would epigenetically repress nuclear receptor subfamily 1, group H, member 4 (FXR gene name) expression through increased CpG methylation. Normal proximal colonic mucosa and normal-appearing adjacent colonic mucosa and colon tumors were collected from wild-type C57BL/6J and Apc-deficient (Apc(Min) (/+)) male mice, respectively. The expression of Fxr, ileal bile acid-binding protein (Ibabp), small heterodimer partner (Shp), and cyclooxygenase-2 (Cox-2) were determined by real-time polymerase chain reaction. In both normal and adjacent colonic mucosa and colon tumors, we measured CpG methylation of Fxr in bisulfonated genomic DNA. In vitro, we measured the impact of APC inactivation and deoxycholic acid (DCA) treatment on FXR expression in human colon cancer HCT-116 cells transfected with silencing RNA for APC and HT-29 cells carrying inactivated APC. In Apc(Min) (/+) mice, constitutive CpG methylation of the Fxrα3/4 promoter was linked to reduced (60-90%) baseline Fxr, Ibabp, and Shp and increased Cox-2 expression in apparently normal adjacent mucosa and colon tumors. Apc knockdown in HCT-116 cells increased cellular myelocytomatosis (c-MYC) and lowered (∼50%) FXR expression, which was further reduced (∼80%) by DCA. In human HCT-116 but not HT-29 colon cancer cells, DCA induced FXR expression and lowered CpG methylation of FXR. We conclude that the loss of APC function favors the silencing of FXR expression through CpG hypermethylation in mouse colonic mucosa and human colon cells

MicroRNAs as Regulator of Signaling Networks in Metastatic Colon Cancer

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Wang, Jian; Du, Yong; Liu, Xiaoming; Cho, William C.; Yang, Yinxue

2015-01-01

MicroRNAs (miRNAs) are a class of small, noncoding RNA molecules capable of regulating gene expression translationally and/or transcriptionally. A large number of evidence have demonstrated that miRNAs have a functional role in both physiological and pathological processes by regulating the expression of their target genes. Recently, the functionalities of miRNAs in the initiation, progression, angiogenesis, metastasis, and chemoresistance of tumors have gained increasing attentions. Particularly, the alteration of miRNA profiles has been correlated with the transformation and metastasis of various cancers, including colon cancer. This paper reports the latest findings on miRNAs involved in different signaling networks leading to colon cancer metastasis, mainly focusing on miRNA profiling and their roles in PTEN/PI3K, EGFR, TGFβ, and p53 signaling pathways of metastatic colon cancer. The potential of miRNAs used as biomarkers in the diagnosis, prognosis, and therapeutic targets in colon cancer is also discussed. PMID:26064956

MicroRNAs as Regulator of Signaling Networks in Metastatic Colon Cancer.

Science.gov (United States)

Wang, Jian; Du, Yong; Liu, Xiaoming; Cho, William C; Yang, Yinxue

2015-01-01

MicroRNAs (miRNAs) are a class of small, noncoding RNA molecules capable of regulating gene expression translationally and/or transcriptionally. A large number of evidence have demonstrated that miRNAs have a functional role in both physiological and pathological processes by regulating the expression of their target genes. Recently, the functionalities of miRNAs in the initiation, progression, angiogenesis, metastasis, and chemoresistance of tumors have gained increasing attentions. Particularly, the alteration of miRNA profiles has been correlated with the transformation and metastasis of various cancers, including colon cancer. This paper reports the latest findings on miRNAs involved in different signaling networks leading to colon cancer metastasis, mainly focusing on miRNA profiling and their roles in PTEN/PI3K, EGFR, TGFβ, and p53 signaling pathways of metastatic colon cancer. The potential of miRNAs used as biomarkers in the diagnosis, prognosis, and therapeutic targets in colon cancer is also discussed.

MicroRNAs as Regulator of Signaling Networks in Metastatic Colon Cancer

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Jian Wang

2015-01-01

Full Text Available MicroRNAs (miRNAs are a class of small, noncoding RNA molecules capable of regulating gene expression translationally and/or transcriptionally. A large number of evidence have demonstrated that miRNAs have a functional role in both physiological and pathological processes by regulating the expression of their target genes. Recently, the functionalities of miRNAs in the initiation, progression, angiogenesis, metastasis, and chemoresistance of tumors have gained increasing attentions. Particularly, the alteration of miRNA profiles has been correlated with the transformation and metastasis of various cancers, including colon cancer. This paper reports the latest findings on miRNAs involved in different signaling networks leading to colon cancer metastasis, mainly focusing on miRNA profiling and their roles in PTEN/PI3K, EGFR, TGFβ, and p53 signaling pathways of metastatic colon cancer. The potential of miRNAs used as biomarkers in the diagnosis, prognosis, and therapeutic targets in colon cancer is also discussed.

Right Versus Left Colon Cancer Biology: Integrating the Consensus Molecular Subtypes.

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Lee, Michael S; Menter, David G; Kopetz, Scott

2017-03-01

Although clinical management of colon cancer generally has not accounted for the primary tumor site, left-sided and right-sided colon cancers harbor different clinical and biologic characteristics. Right-sided colon cancers are more likely to have genome-wide hypermethylation via the CpG island methylator phenotype (CIMP), hypermutated state via microsatellite instability, and BRAF mutation. There are also differential exposures to potential carcinogenic toxins and microbiota in the right and left colon. Gene expression analyses further shed light on distinct biologic subtypes of colorectal cancers (CRCs), with 4 consensus molecular subtypes (CMSs) identified. Importantly, these subtypes are differentially distributed between right- and left-sided CRCs, with greater proportions of the "microsatellite unstable/immune" CMS1 and the "metabolic" CMS3 subtypes found in right-sided colon cancers. This review summarizes important biologic distinctions between right- and left-sided CRCs that likely impact prognosis and may predict for differential responses to biologic therapy. Given the inferior prognosis of stage III-IV right-sided CRCs and emerging data suggesting that anti-epidermal growth factor receptor antibody therapy is associated with worse survival in right-sided stage IV CRCs compared with left-sided cancers, these biologic differences between right- and left-sided CRCs provide critical context and may provide opportunities to personalize therapy. Copyright © 2017 by the National Comprehensive Cancer Network.

[Efficacy evaluation of laparoscopic complete mesocolic excision for transverse colon cancer].

Science.gov (United States)

Cao, Jinpeng; Ji, Yong; Peng, Xiang; Wu, Wenhui; Cheng, Longqing; Zhou, Yonghui; Yang, Ping

2017-05-25

To investigate the safety, feasibility and long-term outcomes of laparoscopic complete mesocolic excision for the transverse colon cancer. Clinical data of 61 patients who underwent laparoscopic complete mesocolic excision for transverse colon cancer (transverse group) in our department from January 2011 to January 2014 were retrospectively analyzed, which were compared with those of 155 patients undergoing laparoscopic complete mesocolic excision for ascending colon cancer (ascending group) and 230 patients undergoing laparoscopic complete mesocolic excision for sigmoid colon cancer (sigmoid group). Differences in operative details, postoperative recovery, postoperative complications and long-term survival among 3 groups were evaluated. No significant differences in the baseline information were found among 3 groups(all P>0.05). The average operative time was significantly longer in transverse group as compared to ascending group and sigmoid group [(192.1±58.7) min vs. (172.2±54.7) min and (169.1±53.6) min]( P0.05). A total of 436 patients received postoperative follow-up of median 36 (5 to 67) months. The overall 5-year survival rate was 73.1%, 73.7% and 74.8%, and the 5-year disease-free survival rate was 71.5%, 71.1% and 72.7% in transverse, ascending and sigmoid colon cancer groups respectively, whose differences were not significant among 3 groups (all P>0.05). Laparoscopic complete mesocolic excision for transverse colon cancer is safe and feasible with slightly longer operation time, and has quite good long-term oncologic efficacy.

The msi and the role of fascism in Italian political culture

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Ferran GALLEGO

2013-05-01

Full Text Available This paper analyzes the role of the italian social movement in Italy (MSI in the twentieth century. The key to understand its influence would lie in the peculiarities of the political regime emerged from the ruins of fascism. With the proclamation of the republic many fascists enrolled in the ranks of the christian Democrats and other parties of the right, leaving the MSI as sole heir of fascism. That did not stop working with the christian Democrats through the strategy of «inserimento». When the christian Democrats began their approach to the italian socialist Party, the MSI was clearly excluded and located in a relatively marginal position. Its later resurgence may be explained considering the radical changes in italian politics in the sixties and seventies; circumstances which favoured the arrival of Giorgio Almirante as leader of MSI in 1969. In that period, the MSI presented itself as the political party of restored order and ready to fight subversion (communist itself. During the 80s, the MSI moved between the ‘strategy-Party Protest’ leaded by Almirante and the idea of a ‘civil society Party’ defended by Rauti. In the end, the MSI, after the change of leadership of Almirante by Gianfranco Fini, began a new path which stated loyalty to the values of fascism, strengthened by the crisis of communism. This MSI new discourse eased its growth in circumstances in which the traditional parties and the Italian Republican system as a whole were practically about to collapse. Subsequently, the post-fascist Alianza Nacional emerged; a political formation which later on merged into Forza Italia, leaded by Silvio Berlusconi.

Dietary risk factors for colon and rectal cancers: a comparative case-control study.

Science.gov (United States)

Wakai, Kenji; Hirose, Kaoru; Matsuo, Keitaro; Ito, Hidemi; Kuriki, Kiyonori; Suzuki, Takeshi; Kato, Tomoyuki; Hirai, Takashi; Kanemitsu, Yukihide; Tajima, Kazuo

2006-05-01

In Japan, the incidence rate of colon cancer has more rapidly increased than that of rectal cancer. The differential secular trends may be due to different dietary factors in the development of colon and rectal cancers. To compare dietary risk factors between colon and rectal cancers, we undertook a case-control study at Aichi Cancer Center Hospital, Japan. Subjects were 507 patients with newly diagnosed colon (n = 265) and rectal (n = 242) cancers, and 2,535 cancer-free outpatients (controls). Intakes of nutrients and food groups were assessed with a food frequency questionnaire, and multivariate-adjusted odds ratios (ORs) were estimated using unconditional logistic models. We found a decreasing risk of colon cancer with increasing intakes of calcium and insoluble dietary fiber; the multivariate ORs across quartiles of intake were 1.00, 0.90, 0.80, and 0.67 (trend p = 0.040), and 1.00, 0.69, 0.64, and 0.65 (trend p = 0.027), respectively. For rectal cancer, a higher consumption of carotene and meat was associated with a reduced risk; the corresponding ORs were 1.00, 1.10, 0.71, and 0.70 for carotene (trend p = 0.028), and 1.00, 0.99, 0.68, and 0.72 for meat (trend p = 0.036). Carbohydrate intake was positively correlated with the risk of rectal cancer (ORs over quartiles: 1.00, 1.14, 1.42, and 1.54; trend p = 0.048). This association was stronger in women, while fat consumption was inversely correlated with the risk of female colon and rectal cancers. Dietary risk factors appear to considerably differ between colon and rectal cancers.

Right colon cancer: Left behind.

Science.gov (United States)

Gervaz, P; Usel, M; Rapiti, E; Chappuis, P; Neyroud-Kaspar, I; Bouchardy, C

2016-09-01

Prognosis of colon cancer (CC) has steadily improved during the past three decades. This trend, however, may vary according to proximal (right) or distal (left) tumor location. We studied if improvement in survival was greater for left than for right CC. We included all CC recorded at the Geneva population-based registry between 1980 and 2006. We compared patients, tumor and treatment characteristics between left and right CC by logistic regression and compared CC specific survival by Cox models taking into account putative confounders. We also compared changes in survival between CC location in early and late years of observation. Among the 3396 CC patients, 1334 (39%) had right-sided and 2062 (61%) left-sided tumors. In the early 1980s, 5-year specific survival was identical for right and left CCs (49% vs. 48%). During the study period, a dramatic improvement in survival was observed for patients with left-sided cancers (Hazard ratio [HR]: 0.42, 95% confidence interval [CI]: 0.29-0.62, p colon cancer patients, those with right-sided lesions have by far the worse prognosis. Change of strategic management in this subgroup is warranted. Copyright © 2016 Elsevier Ltd. All rights reserved.

EGFR regulation of colon cancer stem-like cells during aging and in response to the colonic carcinogen dimethylhydrazine.

Science.gov (United States)

Nautiyal, Jyoti; Du, Jianhua; Yu, Yingjie; Kanwar, Shailender S; Levi, Edi; Majumdar, Adhip P N

2012-04-01

One of the most consistent pathological conditions in the gastrointestinal tract with advancing age is malignancy, particularly gastrointestinal cancers, the incidence of which increases sharply with aging. Although the reasons for the age-related rise in colorectal cancer are not fully understood, we hypothesize that aging increases susceptibility of the colon to carcinogen(s)/toxicant(s), leading to an increase in cancer stem-like cells (CSLCs) that express cancer stem cell markers, in the colonic mucosa. The current study demonstrates that aging is associated with increased expression of several colon CSLC markers [CD44, CD166, and aldehyde dehydrogenase 1 (ALDH-1)] and a higher proportion of cells expressing these markers. Aging is also accompanied by increased expression of miR-21 in colon. These increases are further increased in response to the colonic carcinogen dimethylhydrazine (DMH). Aging is also associated with increased tyrosine-phosphorylated epidermal growth factor receptor (EGFR). Inhibition of EGFR using the EGFR inhibitor cetuximab abrogated the age-related increase in CD166 and ALDH-1 as well as miRNA (miR)-21. Our results provide new evidence that aging and DMH are associated with increases in CSLC biomarkers and miR21, each of which have been linked to colorectal cancer. EGFR inhibition attenuates these changes, indicating a role for EGFR in age- and mutagen-associated changes in CSLCs.