Science.gov

Sample records for colon cancer surveillance

  1. Surveillance and Survivorship after Treatment for Colon Cancer

    PubMed Central

    Makhoul, Rami; Alva, Suraj; Wilkins, Kirsten B.

    2015-01-01

    Colorectal cancer is the third most common cancer diagnosed in the United States. Majority of patients have localized disease that is amenable to curative resection. Disease recurrence remains a major concern after resection. In addition, patients are at an increased risk for developing a second or metachronous colon cancer. The principal goal of surveillance following treatment of colon cancer is to improve disease-free and overall survival. Survivorship is a distinct phase following surveillance to help improve quality of life and promote longevity. PMID:26648797

  2. Practice Guideline for the Surveillance of Patients After Curative Treatment of Colon and Rectal Cancer.

    PubMed

    Steele, Scott R; Chang, George J; Hendren, Samantha; Weiser, Marty; Irani, Jennifer; Buie, W Donald; Rafferty, Janice F

    2015-08-01

    Current evidence suggests improved rates of curative secondary treatment following identification of recurrence among patients who participate in a surveillance program after initial curative resection of colon or rectal cancer. The newer data show that surveillance CEA, chest and liver imaging,and colonoscopy can also improve survival through early diagnosis of recurrence; thus, these modalities are now included in the current guideline. Although the optimum strategy of surveillance for office visits, CEA, chest and liver imaging, and colonoscopy is not yet defined, routine surveillance does improve the detection of recurrence that can be resected with curative intent. Recommended surveillance schedules are shown in Table 4. However, the factors to be considered when recommending surveillance include underlying risk for recurrence, patient comorbidity, and the ability to tolerate major surgery to resect recurrent disease or palliative chemotherapy, performance status, physiologic age, preference, and compliance. The success of surveillance for early detection of curable recurrence will depend on patient and provider involvement to adhere to the surveillance schedule and avoid unnecessary examination. It should be noted that, after curative resection of colorectal cancer, patients are still at risk for other common malignancies(lung, breast, cervix, prostate) for which standard screening recommendations should be observed and measures to maintain general health (risk reduction for cardiovascular disease, eg, cessation of smoking, control of blood pressure and diabetes mellitus, balanced diet, regular exercise and sleep, and flu vaccines) should be recommended.

  3. Colon cancer

    MedlinePlus

    Colorectal cancer; Cancer - colon; Rectal cancer; Cancer - rectum; Adenocarcinoma - colon; Colon - adenocarcinoma ... In the United States, colorectal cancer is one of the leading causes of deaths due to cancer. Early diagnosis can often lead to a complete cure. Almost ...

  4. Early stage colon cancer.

    PubMed

    Freeman, Hugh James

    2013-12-14

    Evidence has now accumulated that colonoscopy and removal of polyps, especially during screening and surveillance programs, is effective in overall risk reduction for colon cancer. After resection of malignant pedunculated colon polyps or early stage colon cancers, long-term repeated surveillance programs can also lead to detection and removal of asymptomatic high risk advanced adenomas and new early stage metachronous cancers. Early stage colon cancer can be defined as disease that appears to have been completely resected with no subsequent evidence of involvement of adjacent organs, lymph nodes or distant sites. This differs from the clinical setting of an apparent "curative" resection later pathologically upstaged following detection of malignant cells extending into adjacent organs, peritoneum, lymph nodes or other distant sites, including liver. This highly selected early stage colon cancer group remains at high risk for subsequent colon polyps and metachronous colon cancer. Precise staging is important, not only for assessing the need for adjuvant chemotherapy, but also for patient selection for continued surveillance. With advanced stages of colon cancer and a more guarded outlook, repeated surveillance should be limited. In future, novel imaging technologies (e.g., confocal endomicroscopy), coupled with increased pathological recognition of high risk markers for lymph node involvement (e.g., "tumor budding") should lead to improved staging and clinical care.

  5. Colon cancer - resources

    MedlinePlus

    Resources - colon cancer ... The following organizations are good resources for information on colon cancer : American Cancer Society -- www.cancer.org/cancer/colonandrectumcancer/index Colon Cancer Alliance -- www.ccalliance.org National ...

  6. Stages of Colon Cancer

    MedlinePlus

    ... for information about colorectal cancer in children. Health history affects the risk of developing colon cancer. Anything ... colorectal cancer include the following: Having a family history of colon or rectal cancer in a first- ...

  7. Surveillance of colonic polyps: Are we getting it right?

    PubMed Central

    Bonnington, Stewart N; Rutter, Matthew D

    2016-01-01

    Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. The identification of colonic polyps can reduce CRC mortality through earlier diagnosis of cancers and the removal of polyps: the precursor lesion of CRC. Following the finding and removal of colonic polyps at an initial colonoscopy, some patients are at an increased risk of developing CRC in the future. This is the rationale for post-polypectomy surveillance colonoscopy. However, not all individuals found to have colonic adenomas have a risk of CRC higher than that of the general population. This review examines the literature on post-polypectomy surveillance including current international clinical guidelines. The potential benefits of surveillance procedures must be weighed against the burden of colonoscopy: resource use, the potential for patient discomfort, and the risk of complications. Therefore surveillance colonoscopy is best utilised in a selected group of individuals at a high risk of developing cancer. Further study is needed into the specific factors conferring higher risk as well as the efficacy of surveillance in mitigating this risk. Such evidence will better inform clinicians and patients of the relative benefits of colonoscopic surveillance for the individual. In addition, the decision to continue with surveillance must be informed by the changing profile of risks and benefits of further procedures with the patient’s advancing age. PMID:26877600

  8. Colon cancer screening

    MedlinePlus

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

  9. Understanding your colon cancer risk

    MedlinePlus

    Colon cancer - prevention; Colon cancer - screening ... We do not know what causes colon cancer, but we do know some of the things that may increase the risk of getting it, such as: Age. Your risk increases after ...

  10. Colon cancer - slideshow

    MedlinePlus

    ... ency/presentations/100157.htm Colon cancer - Series—Normal anatomy To use the sharing features on this page, ... Bethesda, MD 20894 U.S. Department of Health and Human Services National Institutes of Health Page last updated: ...

  11. Inflammation and colon cancer.

    PubMed

    Terzić, Janos; Grivennikov, Sergei; Karin, Eliad; Karin, Michael

    2010-06-01

    The connection between inflammation and tumorigenesis is well-established and in the last decade has received a great deal of supporting evidence from genetic, pharmacological, and epidemiological data. Inflammatory bowel disease is an important risk factor for the development of colon cancer. Inflammation is also likely to be involved with other forms of sporadic as well as heritable colon cancer. The molecular mechanisms by which inflammation promotes cancer development are still being uncovered and could differ between colitis-associated and other forms of colorectal cancer. Recent work has elucidated the role of distinct immune cells, cytokines, and other immune mediators in virtually all steps of colon tumorigenesis, including initiation, promotion, progression, and metastasis. These mechanisms, as well as new approaches to prevention and therapy, are discussed in this review.

  12. Get Tested for Colon Cancer: Here's How

    MedlinePlus Videos and Cool Tools

    ... collection below explain colon cancer risk factors, screening tests, and treatments. There are also personal stories from ... Colon Cancer Risk Play Play Colon Cancer: Screening Tests Play Play Colon Cancer Screening Tests: Colonoscopy Play ...

  13. Keep Colon Cancer At Bay

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_164231.html Keep Colon Cancer at Bay Colonoscopy best way to detect disease ... 22, 2017 WEDNESDAY, March 22, 2017 (HealthDay News) -- Colon cancer can be treated and cured if it's diagnosed ...

  14. Active surveillance for prostate cancer.

    PubMed

    Romero-Otero, Javier; García-Gómez, Borja; Duarte-Ojeda, José M; Rodríguez-Antolín, Alfredo; Vilaseca, Antoni; Carlsson, Sigrid V; Touijer, Karim A

    2016-03-01

    It is worth distinguishing between the two strategies of expectant management for prostate cancer. Watchful waiting entails administering non-curative androgen deprivation therapy to patients on development of symptomatic progression, whereas active surveillance entails delivering curative treatment on signs of disease progression. The objectives of the two management strategies and the patients enrolled in either are different: (i) to review the role of active surveillance as a management strategy for patients with low-risk prostate cancer; and (ii) review the benefits and pitfalls of active surveillance. We carried out a systematic review of active surveillance for prostate cancer in the literature using the National Center for Biotechnology Information's electronic database, PubMed. We carried out a search in English using the terms: active surveillance, prostate cancer, watchful waiting and conservative management. Selected studies were required to have a comprehensive description of the demographic and disease characteristics of the patients at the time of diagnosis, inclusion criteria for surveillance, and a protocol for the patients' follow up. Review articles were included, but not multiple papers from the same datasets. Active surveillance appears to reduce overtreatment in patients with low-risk prostate cancer without compromising cancer-specific survival at 10 years. Therefore, active surveillance is an option for select patients who want to avoid the side-effects inherent to the different types of immediate treatment. However, inclusion criteria for active surveillance and the most appropriate method of monitoring patients on active surveillance have not yet been standardized.

  15. Advances in colon cancer.

    PubMed

    Levin, Mark

    2003-06-01

    From May 29 to June 5, 2003, the American Society of Clinical Oncology held its 39th Annual Meeting in Chicago, Illinois, U.S.A. The meeting was devoted to the presentation of advances in clinical sciences, diagnosis, prevention and management of malignant disorders, and brings together investigators, clinicians, policy makers and other professionals interested in the science and impact of cancer worldwide. This report will be presented in two parts, the first focusing of colon cancer, and the second on breast cancer will be published in the next issue of Drug News & Perspectives.

  16. CT findings of colonic complications associated with colon cancer.

    PubMed

    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.

  17. Surveillance of Anal Canal Cancers.

    PubMed

    Adams, Richard

    2017-01-01

    Anal squamous cell cancer is most frequently a locoregional disease that is amenable to curative therapy in a majority of fit patients. Complete response rates after chemoradiotherapy (CRT) are good, with up to 75% of patients with no evidence of relapse on surveillance. Relapse is most frequently locoregional and is often amendable to salvage surgery with curative intent. Effective surveillance attempts to improve outcomes by identifying recurrent or persistent disease early, managing both acute and late toxicities, and offering reassurance to patients. This article explores the rationale and evidence for surveillance programs after definitive CRT.

  18. Breast and Colon Cancer Family Registries

    Cancer.gov

    The Breast Cancer Family Registry and the Colon Cancer Family Registry were established by the National Cancer Institute as a resource for investigators to use in conducting studies on the genetics and molecular epidemiology of breast and colon cancer.

  19. Selenium, Folate, and Colon Cancer

    PubMed Central

    Connelly-Frost, Alexandra; Poole, Charles; Satia, Jessie A.; Kupper, Lawrence L.; Millikan, Robert C.; Sandler, Robert S.

    2009-01-01

    Background Selenium is an essential trace element which has been implicated in cancer risk; however, study results have been inconsistent with regard to colon cancer. Our objectives were to 1) investigate the association between selenium and colon cancer 2) evaluate possible effect measure modifiers and 3) evaluate potential biases associated with the use of post-diagnostic serum selenium measures Methods The North Carolina Colon Cancer Study is a large population-based, case-control study of colon cancer in North Carolina between 1996 and 2000 (n=1,691). Nurses interviewed patients about diet and lifestyle and drew blood specimens which were used to measure serum selenium. Results Individuals who had both high serum selenium (>140 mcg/L) and high reported folate (>354 mcg/day), had a reduced relative risk of colon cancer (OR=0.5, 95% CI=0.4,0.8). The risk of colon cancer for those with high selenium and low folate was approximately equal to the risk among those with low selenium and low folate (OR=1.1, 95% CI=0.7,1.5) as was the risk for those with low selenium and high folate (OR=0.9, 95% CI=0.7–1.2). We did not find evidence of bias due to weight loss, stage at diagnosis, or time from diagnosis to selenium measurement. Conclusion High levels of serum selenium and reported folate jointly were associated with a substantially reduced risk of colon cancer. Folate status should be taken into account when evaluating the relation between selenium and colon cancer in future studies. Importantly, weight loss, stage at diagnosis, or time from diagnosis to blood draw did not appear to produce strong bias in our study. PMID:19235033

  20. Cost-effectiveness and quality of life in surgeon versus general practitioner-organised colon cancer surveillance: a randomised controlled trial

    PubMed Central

    Augestad, Knut Magne; Norum, Jan; Dehof, Stefan; Aspevik, Ranveig; Ringberg, Unni; Nestvold, Torunn; Vonen, Barthold; Skrøvseth, Stein Olav; Lindsetmo, Rolv-Ole

    2013-01-01

    Objective To assess whether colon cancer follow-up can be organised by general practitioners (GPs) without a decline in the patient's quality of life (QoL) and increase in cost or time to cancer diagnoses, compared to hospital follow-up. Design Randomised controlled trial. Setting Northern Norway Health Authority Trust, 4 trusts, 11 hospitals and 88 local communities. Participants Patients surgically treated for colon cancer, hospital surgeons and community GPs. Intervention 24-month follow-up according to national guidelines at the community GP office. To ensure a high follow-up guideline adherence, a decision support tool for patients and GPs were used. Main outcome measures Primary outcomes were QoL, measured by the global health scales of the European Organisation for Research and Treatment of Cancer QoL Questionnaire (EORTC QLQ C-30) and EuroQol-5D (EQ-5D). Secondary outcomes were cost-effectiveness and time to cancer diagnoses. Results 110 patients were randomised to intervention (n=55) or control (n=55), and followed by 78 GPs (942 follow-up months) and 70 surgeons (942 follow-up months), respectively. Compared to baseline, there was a significant improvement in postoperative QoL (p=0.003), but no differences between groups were revealed (mean difference at 1, 3, 6, 9, 12, 15, 18, 21 and 24-month follow-up appointments): Global Health; Δ−2.23, p=0.20; EQ-5D index; Δ−0.10, p=0.48, EQ-5D VAS; Δ−1.1, p=0.44. There were no differences in time to recurrent cancer diagnosis (GP 35 days vs surgeon 45 days, p=0.46); 14 recurrences were detected (GP 6 vs surgeon 8) and 7 metastases surgeries performed (GP 3 vs surgeon 4). The follow-up programme initiated 1186 healthcare contacts (GP 678 vs surgeon 508), 1105 diagnostic tests (GP 592 vs surgeon 513) and 778 hospital travels (GP 250 vs surgeon 528). GP organised follow-up was associated with societal cost savings (£8233 vs £9889, p<0.001). Conclusions GP-organised follow-up was associated with no

  1. Cholesterol metabolism and colon cancer.

    PubMed

    Broitman, S A; Cerda, S; Wilkinson, J

    1993-01-01

    While epidemiologic and concordant experimental data indicate a direct relationship between dietary fat (and presumably caloric) intake and the development of colon cancer, the effect of dietary cholesterol on this disease is still not clear. However, there appears to be a developing literature concerning an inverse relationship between serum and plasma cholesterol levels, and the risk for colon cancer. Findings that low serum cholesterol levels are apparent as early as ten years prior to the detection of colon cancer implies that sub clinical disease is probably not involved initially in this process. The possibility of low serum cholesterol as a bio-marker was considered in epidemiologic studies which focused upon obese men with lower than normal serum cholesterol levels who were found to be at increased risk to colon cancer. While the relationship between low serum cholesterol and colonic or intestinal cholesterol metabolism is presently not understood, current genetic studies provide a promising though as yet unexplored potential association. Alterations which occur during the developmental progression of colonic cancer include changes in chromosome 5, which also carries two genes vital to the biosynthesis and regulation of systemic and cellular cholesterol metabolism, 3-hydroxy-3-methylglutaryl coenzyme A synthase, and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoA R). Regulation of cholesterol metabolism in intestinal cells in vivo and in vitro varies from that seen in normal fibroblasts or hepatocytes in terms of exogenous sources of cholesterol and how these sources regulate internal synthesis. Colonic cancer cells have been used to assess small bowel enterocyte cholesterol metabolism, which has been possible because of their ability to differentiate in culture, however information regarding true colonic enterocyte cholesterol metabolism is relatively scarce. Colonic cancer cells have been shown to possess a diminished or nonexistent ability to use

  2. Testicular Cancer Treatments: Surveillance

    MedlinePlus

    ... are TC clean, and your first line of defense are these testing regimens. If you do all the tests, this is not a risky choice. Click on this to go back to the TCRC main page: This page was last updated on Dec 05, 2012 Copyright © 1997 - 2012 The Testicular Cancer Resource Center , All Rights Reserved

  3. Preventing Second Cancers in Colon Cancer Survivors

    Cancer.gov

    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.

  4. [Molecular targets in colon cancer].

    PubMed

    Borner, M M

    2006-04-01

    Colorectal cancer is the second leading cause of cancer death in Switzerland. The nihilism that dominated the treatment of these patients for decades has been replaced by a measure of enthusiasm, given recent therapeutic advances. New anticancer drugs such as irinotecan and oxaliplatin have changed the standard chemotherapy treatment of metastatic colorectal cancer. However, the real hype has come from molecular targeted therapy. Identification of cellular processes characteristic of colon cancer has permitted therapeutic targeting with favorable therapeutic index. Inhibition of the epidermal growth factor receptor in the clinic has provided proof of principle that interruption of signal transduction cascades in patients has therapeutic potential. Angiogenesis, especially the vascular endothelial growth factor pathway, has been proven to be another highly successful molecular target. In this article, we will review molecular targets, which are under active clinical investigation in colon cancer.

  5. Optimal follow-up to curative colon and rectal cancer surgery: how and for how long?

    PubMed

    Asgeirsson, Theodor; Zhang, Sen; Senagore, Anthony J

    2010-10-01

    In 2009, the projected incidence for colon and rectal cancers in the United States was 106,100 and 40,870, respectively, and approximately 75% of these patients were treated with curative intent. Surveillance or follow-up after colon and rectal cancer resection serves multiple purposes; however, the primary argument supporting the validity of surveillance is the detection of metachronous and recurrent cancers amenable to curative treatment. The surveillance may provide some comfort for cancer survivors who can be informed that they have no evidence of disease.

  6. Cholesterol excretion and colon cancer.

    PubMed

    Broitman, S A

    1981-09-01

    Populations consuming diets high in fat and cholesterol exhibit a greater incidence of colon cancer than those consuming less fat and cholesterol. Lowering elevated serum cholesterol levels experimentally or clinically is associated with increased large-bowel tumorigenesis. Thus, cholesterol lost to the gut, either dietary or endogenously synthesized, appears to have a role in large-bowel cancer. Whether the effect(s) is mediated by increases in fecal bile acid excretion or some other mechanism is not clear.

  7. Developmental pathways in colon cancer

    PubMed Central

    Bertrand, Fred E.; Angus, C. William; Partis, William J.; Sigounas, George

    2012-01-01

    A hallmark of cancer is reactivation/alteration of pathways that control cellular differentiation during developmental processes. Evidence indicates that WNT, Notch, BMP and Hedgehog pathways have a role in normal epithelial cell differentiation, and that alterations in these pathways accompany establishment of the tumorigenic state. Interestingly, there is recent evidence that these pathways are intertwined at the molecular level, and these nodes of intersection may provide opportunities for effective targeted therapies. This review will highlight the role of the WNT, Notch, BMP and Hedgehog pathways in colon cancer. PMID:23032367

  8. Drugs Approved for Colon and Rectal Cancer

    Cancer.gov

    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.

  9. PET-MRI in Diagnosing Patients With Colon or Rectal Cancer

    ClinicalTrials.gov

    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

  10. Patterns of metastasis in colon and rectal cancer

    PubMed Central

    Riihimäki, Matias; Hemminki, Akseli; Sundquist, Jan; Hemminki, Kari

    2016-01-01

    Investigating epidemiology of metastatic colon and rectal cancer is challenging, because cancer registries seldom record metastatic sites. We used a population based approach to assess metastatic spread in colon and rectal cancers. 49,096 patients with colorectal cancer were identified from the nationwide Swedish Cancer Registry. Metastatic sites were identified from the National Patient Register and Cause of Death Register. Rectal cancer more frequently metastasized into thoracic organs (OR = 2.4) and the nervous system (1.5) and less frequently within the peritoneum (0.3). Mucinous and signet ring adenocarcinomas more frequently metastasized within the peritoneum compared with generic adenocarcinoma (3.8 [colon]/3.2 [rectum]), and less frequently into the liver (0.5/0.6). Lung metastases occurred frequently together with nervous system metastases, whereas peritoneal metastases were often listed with ovarian and pleural metastases. Thoracic metastases are almost as common as liver metastases in rectal cancer patients with a low stage at diagnosis. In colorectal cancer patients with solitary metastases the survival differed between 5 and 19 months depending on T or N stage. Metastatic patterns differ notably between colon and rectal cancers. This knowledge should help clinicians to identify patients in need for extra surveillance and gives insight to further studies on the mechanisms of metastasis. PMID:27416752

  11. Variation in Positron Emission Tomography Use After Colon Cancer Resection

    PubMed Central

    Bailey, Christina E.; Hu, Chung-Yuan; You, Y. Nancy; Kaur, Harmeet; Ernst, Randy D.; Chang, George J.

    2015-01-01

    Purpose: Colon cancer surveillance guidelines do not routinely include positron emission tomography (PET) imaging; however, its use after surgical resection has been increasing. We evaluated the secular patterns of PET use after surgical resection of colon cancer among elderly patients and identified factors associated with its increasing use. Patients and Methods: We used the SEER-linked Medicare database (July 2001 through December 2009) to establish a retrospective cohort of patients age ≥ 66 years who had undergone surgical resection for colon cancer. Postoperative PET use was assessed with the test for trends. Patient, tumor, and treatment characteristics were analyzed using univariable and multivariable logistic regression analyses. Results: Of the 39,221 patients with colon cancer, 6,326 (16.1%) had undergone a PET scan within 2 years after surgery. The use rate steadily increased over time. The majority of PET scans had been performed within 2 months after surgery. Among patients who had undergone a PET scan, 3,644 (57.6%) had also undergone preoperative imaging, and 1,977 (54.3%) of these patients had undergone reimaging with PET within 2 months after surgery. Marriage, year of diagnosis, tumor stage, preoperative imaging, postoperative visit to a medical oncologist, and adjuvant chemotherapy were significantly associated with increased PET use. Conclusion: PET use after colon cancer resection is steadily increasing, and further study is needed to understand the clinical value and effectiveness of PET scans and the reasons for this departure from guideline-concordant care. PMID:25852143

  12. Increasing Breast Cancer Surveillance Among African American Breast Cancer Survivors

    DTIC Science & Technology

    2006-07-01

    the Witness model will be tailored for breast cancer survivors and the peer interventionists (breast cancer survivors and lay health advisors) will be...by a lay health advisor; 4) discussion of concerns and myths about breast cancer and screening /surveillance that are prevalent among AAW; 5) review...Breast cancer screening surveillance Breast cancer screening Treatment/Time of Treatment intention /adherence & physician recommendation

  13. Microbes, microbiota, and colon cancer.

    PubMed

    Sears, Cynthia L; Garrett, Wendy S

    2014-03-12

    Colorectal cancer (CRC) presents a considerable disease burden worldwide. The human colon is also an anatomical location with the largest number of microbes. It is natural, therefore, to anticipate a role for microbes, particularly bacteria, in colorectal carcinogenesis. The increasing accessibility of microbial meta'omics is fueling a surge in our understanding of the role that microbes and the microbiota play in CRC. In this review, we will discuss recent insights into contributions of the microbiota to CRC and explore conceptual frameworks for evaluating the role of microbes in cancer causation. We also highlight new findings on candidate CRC-potentiating species and current knowledge gaps. Finally, we explore the roles of microbial metabolism as it relates to bile acids, xenobiotics, and diet in the etiology and therapeutics of CRC.

  14. Microbes, Microbiota and Colon Cancer

    PubMed Central

    Sears, Cynthia L.; Garrett, Wendy S.

    2014-01-01

    Summary Colorectal cancer (CRC) presents a considerable disease burden worldwide. The human colon is also an anatomical location with the largest number of microbes. It is natural therefore to anticipate a role for microbes, particularly bacteria, in colorectal carcinogenesis. The increasing accessibility of microbial meta’omics is fueling a surge in our understanding of the role that microbes and the microbiota play in CRC. In this review, we will discuss recent insights into contributions of the microbiota to CRC and explore conceptual frameworks for evaluating the role of microbes in cancer causation. We also highlight new findings on candidate CRC-potentiating species and current knowledge gaps. Finally, we explore the roles of microbial metabolism as it relates to bile acids, xenobiotics, and diet in the etiology and therapeutics of CRC. PMID:24629338

  15. Colon Cancer Risk Assessment - Gauss Program

    Cancer.gov

    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.

  16. Increasing Breast Cancer Surveillance among African American Breast Cancer Survivors

    DTIC Science & Technology

    2007-07-01

    predictors of surveillance and follow-up care is Baldwin’s Afrocentric model for describing AA women’s participation in breast and cervical cancer screening...African American women’s participation in breast and cervical cancer early detection and screening. Adv Nurs Sci. 1996;19(2):27Y42. 28. Marin G. Subjective...AD_________________ Award Number: DAMD17-03-1-0454 TITLE: Increasing Breast Cancer Surveillance

  17. Expectant Management (Watchful Waiting) and Active Surveillance for Prostate Cancer

    MedlinePlus

    ... Prostate Cancer Watchful Waiting or Active Surveillance for Prostate Cancer Because prostate cancer often grows very slowly, some ... Away or Comes Back After Treatment More In Prostate Cancer About Prostate Cancer Causes, Risk Factors, and Prevention ...

  18. Redefining Adjuvant Therapy for Colon Cancer

    Cancer.gov

    In this trial, patients with resected stage III colon cancer are being randomly assigned to receive FOLFOX chemotherapy for either 3 or 6 months and to take either a pill called celecoxib or a matching placebo pill for 3 years.

  19. Nuclear Matrix Proteins in Human Colon Cancer

    NASA Astrophysics Data System (ADS)

    Keesee, Susan K.; Meneghini, Marc D.; Szaro, Robert P.; Wu, Ying-Jye

    1994-03-01

    The nuclear matrix is the nonchromatin scaffolding of the nucleus. This structure confers nuclear shape, organizes chromatin, and appears to contain important regulatory proteins. Tissue specific nuclear matrix proteins have been found in the rat, mouse, and human. In this study we compared high-resolution two-dimensional gel electropherograms of nuclear matrix protein patterns found in human colon tumors with those from normal colon epithelia. Tumors were obtained from 18 patients undergoing partial colectomy for adenocarcinoma of the colon and compared with tissue from 10 normal colons. We have identified at least six proteins which were present in 18 of 18 colon tumors and 0 of 10 normal tissues, as well as four proteins present in 0 of 18 tumors and in 10 of 10 normal tissues. These data, which corroborate similar findings of cancer-specific nuclear matrix proteins in prostate and breast, suggest that nuclear matrix proteins may serve as important markers for at least some types of cancer.

  20. Oncolytic reovirus against ovarian and colon cancer.

    PubMed

    Hirasawa, Kensuke; Nishikawa, Sandra G; Norman, Kara L; Alain, Tommy; Kossakowska, Anna; Lee, Patrick W K

    2002-03-15

    Reovirus selectively replicates in and destroys cancer cells with an activated Ras signaling pathway. In this study, we evaluated the feasibility of using reovirus (serotype 3, strain Dearing) as an antihuman colon and ovarian cancer agent. In in vitro studies, reovirus infection in human colon and ovarian cell lines was assessed by cytopathic effect as detected by light microscopy, [(35)S]Methionine labeling of infected cells for viral protein synthesis and progeny virus production by plaque assay. We observed that reovirus efficiently infected all five human colon cancer cell lines (Caco-2, DLD-1, HCT-116, HT-29, and SW48) and four human ovarian cancer cell lines (MDAH2774, PA-1, SKOV3, and SW626) which were tested, but not a normal colon cell line (CCD-18Co) or a normal ovarian cell line (NOV-31). We also observed that the Ras activity in the human colon and ovarian cancer cell lines was elevated compared with that in normal colon and ovarian cell lines. In animal models, intraneoplastic as well as i.v. inoculation of reovirus resulted in significant regression of established s.c. human colon and ovarian tumors implanted at the hind flank. Histological studies revealed that reovirus infection in vivo was restricted to tumor cells, whereas the surrounding normal tissue remained uninfected. Additionally, in an i.p. human ovarian cancer xenograft model, inhibition of ascites tumor formation and the survival of animals treated with live reovirus was significantly greater than of control mice treated with UV-inactivated reovirus. Reovirus infection in ex vivo primary human ovarian tumor surgical samples was also confirmed, further demonstrating the potential of reovirus therapy. These results suggest that reovirus holds promise as a novel agent for human colon and ovarian cancer therapy.

  1. Neuropilin-1 in Human Colon Cancer

    PubMed Central

    Parikh, Alexander A.; Fan, Fan; Liu, Wen Biao; Ahmad, Syed A.; Stoeltzing, Oliver; Reinmuth, Niels; Bielenberg, Diane; Bucana, Corazon D.; Klagsbrun, Michael; Ellis, Lee M.

    2004-01-01

    Neuropilin-1 (NRP-1), a recently identified co-receptor for vascular endothelial growth factor, is expressed by several nongastrointestinal tumor types and enhances prostate cancer angiogenesis and growth in preclinical models. We investigated the expression and regulation of NRP-1 and the effect of NRP-1 overexpression on angiogenesis and growth of human colon adenocarcinoma by immunohistochemistry and in situ hybridization. NRP-1 was expressed in 20 of 20 human colon adenocarcinoma specimens but not in the adjacent nonmalignant colonic mucosa. By reverse transcriptase-polymerase chain reaction analysis, NRP-1 mRNA was expressed in seven of seven colon adenocarcinoma cell lines. Subcutaneous xenografts of stably transfected KM12SM/LM2 human colon cancer cells overexpressing NRP-1 led to increased tumor growth and angiogenesis in nude mice. In in vitro assays, conditioned medium from NRP-1-transfected cell lines led to an increase in endothelial cell migration, but did not affect endothelial cell growth. Epidermal growth factor (EGF) led to induction of NRP-1 in human colon adenocarcinoma cells and selective blockade of the epidermal growth factor receptor (EGFR) decreased constitutive and EGF-induced NRP-1 expression. Blockade of the Erk 1/2 and P38 mitogen-activated protein kinase signaling pathways also led to a decrease in constitutive and EGF-induced NRP-1 expression. These findings demonstrate the ubiquitous expression of NRP-1 in human colon cancer and suggest that NRP-1 may contribute to colon cancer angiogenesis and growth. This study also suggests that EGF and mitogen-activated protein kinase signaling pathways play an important role in NRP-1 regulation in colon cancer cells. PMID:15161648

  2. Skin Cancer Surveillance Behaviors Among Childhood Cancer Survivors.

    PubMed

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

    2016-03-01

    The risk of developing skin cancer is elevated among childhood cancer survivors (CCS), particularly among those treated with radiation. This survey study examined the skin cancer surveillance behaviors of 94 CCS. Approximately 48% of CCS had ever conducted skin self-examination (SSE) and 31% had ever received a physician skin examination. Rates of physician skin examination were 2.5 times higher among CCS treated with radiation compared to those without radiation. However, rates of SSEs did not differ based on treatment history. These findings highlight the need to promote skin cancer surveillance as an important aspect of CCS survivorship care.

  3. Melanosis coli in patients with colon cancer

    PubMed Central

    Biernacka-Wawrzonek, Dorota; Stępka, Michał; Tomaszewska, Alicja; Ehrmann-Jóśko, Agnieszka; Chojnowska, Natalia; Muszyński, Jacek

    2016-01-01

    Introduction 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. PMID:28337232

  4. Northeast Regional Cancer Institute's Cancer Surveillance and Risk Factor Program

    SciTech Connect

    Lesko, Samuel M.

    2007-07-31

    OBJECTIVES The Northeast Regional Cancer Institute is conducting a program of ongoing epidemiologic research to address cancer disparities in northeast Pennsylvania. Of particular concern are disparities in the incidence of, stage at diagnosis, and mortality from colorectal cancer. In northeast Pennsylvania, age-adjusted incidence and mortality rates for colorectal cancer are higher, and a significantly smaller proportion of new colorectal cancer cases are diagnosed with local stage disease than is observed in comparable national data. Further, estimates of the prevalence of colorectal cancer screening in northeast Pennsylvania are lower than the US average. The Northeast Regional Cancer Institute’s research program supports surveillance of common cancers, investigations of cancer risk factors and screening behaviors, and the development of resources to further cancer research in this community. This project has the following specific objectives: I. To conduct cancer surveillance in northeast Pennsylvania. a. To monitor incidence and mortality for all common cancers, and colorectal cancer, in particular, and b. To document changes in the stage at diagnosis of colorectal cancer in this high-risk, underserved community. II. To conduct a population-based study of cancer risk factors and screening behavior in a six county region of northeast Pennsylvania. a. To monitor and document changes in colorectal cancer screening rates, and b. To document the prevalence of cancer risk factors (especially factors that increase the risk of colorectal cancer) and to identify those risk factors that are unusually common in this community. APPROACH Cancer surveillance was conducted using data from the Northeast Regional Cancer Institute’s population-based Regional Cancer Registry, the Pennsylvania Cancer Registry, and NCI’s SEER program. For common cancers, incidence and mortality were examined by county within the region and compared to data for similar populations in the US

  5. Colon resection for ovarian cancer: intraoperative decisions.

    PubMed

    Hoffman, Mitchel S; Zervose, Emmanuel

    2008-11-01

    To discuss the benefits and morbidity of and indications for colon resection during cytoreductive operations for ovarian cancer. The history of cytoreductive surgery for ovarian cancer is discussed, with special attention to the incorporation of colon resection. Literature regarding cytoreductive surgery for ovarian cancer is then reviewed, again with attention to the role of colon resection. The focus of the review is directed at broad technical considerations and rationales, for both primary and secondary cytoreduction. Over the past 15 to 20 years the standard cytoreductive operation for ovarian cancer has shifted from an abdominal hysterectomy with bilateral salpingo-oophorectomy and omentectomy to an en bloc radical resection of the pelvic tumor and an omentectomy, and more recently to include increasing use of extensive upper abdominal surgery. En bloc pelvic resection frequently includes rectosigmoid resection, almost always accompanied by a primary anastomosis. Other portions of the colon are at risk for metastatic involvement and sometimes require resection in order to achieve optimal cytoreduction. The data regarding colon resection for the purpose of surgical cytoreduction of ovarian cancer are conflicting (in terms of benefit) and all retrospective. However, the preponderance of information supports a benefit in terms of survival when cytoreduction is clearly optimal. Similar to primary surgery, benefit from secondary cytoreduction of ovarian cancer occurs when only a small volume of disease is left behind. The preponderance of data suggests that colon resection to achieve optimal cytoreduction has a positive impact on survival. In order to better understand the role of colon resection as well as other extensive cytoreductive procedures for ovarian cancer, it will be important to continue to improve our understanding of prognostic variables such as the nuances of metastatic bowel involvement in order to better guide appropriate surgical management.

  6. How to improve colon cancer screening rates

    PubMed Central

    Alberti, Luiz Ronaldo; Garcia, Diego Paim Carvalho; Coelho, Debora Lucciola; De Lima, David Correa Alves; Petroianu, Andy

    2015-01-01

    Colorectal carcinoma is a common cause of death throughout the world and may be prevented by routine control, which can detect precancerous neoplasms and early cancers before they undergo malignant transformation or metastasis. Three strategies may improve colon cancer screening rates: convince the population about the importance of undergoing a screening test; achieve higher efficacy in standard screening tests and make them more available to the community and develop new more sensitive and efficacious screening methods and make them available as routine tests. In this light, the present study seeks to review these three means through which to increase colon cancer screening rates. PMID:26688708

  7. Screening for and surveillance of gastric cancer.

    PubMed

    Compare, Debora; Rocco, Alba; Nardone, Gerardo

    2014-10-14

    Although the prevalence of gastric cancer (GC) progressively decreased during the last decades, due to improved dietary habit, introduction of food refrigeration and recovered socio-economic level, it still accounts for 10% of the total cancer-related deaths. The best strategy to reduce the mortality for GC is to schedule appropriate screening and surveillance programs, that rises many relevant concerns taking into account its worldwide variability, natural history, diagnostic tools, therapeutic strategies, and cost-effectiveness. Intestinal-type, the most frequent GC histotype, develops through a multistep process triggered by Helicobacter pylori (H. pylori) and progressing from gastritis to atrophy, intestinal metaplasia (IM), and dysplasia. However, the majority of patients infected with H. pylori and carrying premalignant lesions do not develop GC. Therefore, it remains unclear who should be screened, when the screening should be started and how the screening should be performed. It seems reasonable that screening programs should target the general population in eastern countries, at high prevalence of GC and the high-risk subjects in western countries, at low prevalence of GC. As far as concern surveillance, currently, we are lacking of standardized international recommendations and many features have to be defined regarding the optimal diagnostic approach, the patients at higher risk, the best timing and the cost-effectiveness. Anyway, patients with corpus atrophic gastritis, extensive incomplete IM and dysplasia should enter a surveillance program. At present, screening and surveillance programs need further studies to draw worldwide reliable recommendations and evaluate the impact on mortality for GC.

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

    ClinicalTrials.gov

    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

  9. External Beam Radiotherapy for Colon Cancer: Patterns of Care

    SciTech Connect

    Dunn, Emily F.; Kozak, Kevin R.; Moody, John S.

    2010-04-15

    Purpose: Despite its common and well characterized use in other gastrointestinal malignancies, little is known about radiotherapy (RT) use in nonmetastatic colon cancer in the United States. To address the paucity of data regarding RT use in colon cancer management, we examined the RT patterns of care in this patient population. Methods and Materials: Patients with nonmetastatic colon cancer, diagnosed between 1988 and 2005, were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate methods were used to identify factors associated with RT use. Results: On univariate analysis, tumor location, age, sex, race, T stage, N stage, and geographic location were each associated with differences in RT use (all p < 0.01). In general, younger patients, male patients, and patients with more advanced disease were more likely to receive RT. On multivariate analysis, tumor location, age, gender, T and N stage, time of diagnosis and geographic location were significantly associated with RT use (all p < 0.001). Race, however, was not associated with RT use. On multivariate analysis, patients diagnosed in 1988 were 2.5 times more likely to receive RT than those diagnosed in 2005 (p = 0.001). Temporal changes in RT use reflect a responsiveness to evolving evidence related to the therapeutic benefits of adjuvant RT. Conclusions: External beam RT is infrequently used for colon cancer, and its use varies according to patient and tumor characteristics. RT use has declined markedly since the late 1980s; however, it continues to be used for nonmetastatic disease in a highly individualized manner.

  10. Family History of Colon Cancer Calls for Earlier Screening

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_164202.html Family History of Colon Cancer Calls for Earlier Screening ... 2017 (HealthDay News) -- If you've got a family history of colon or rectal cancers, you probably ...

  11. Enterobacter Strains Might Promote Colon Cancer.

    PubMed

    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.

  12. Treatment Option Overview (Colon Cancer)

    MedlinePlus

    ... given chemotherapy or radiation therapy after surgery to kill any cancer cells that are left. Treatment given ... of a special probe with tiny electrodes that kill cancer cells . Sometimes the probe is inserted directly ...

  13. General Information about Colon Cancer

    MedlinePlus

    ... D Resources Conducting Clinical Trials Statistical Tools and Data Terminology Resources NCI Data Catalog Cryo-EM NCI's Role in Cancer Research ... major research initiatives R&D Resources Tools and data sets for researchers Research by Cancer Type Find ...

  14. Colon cancer stem cells: controversies and perspectives.

    PubMed

    Puglisi, Maria Ausiliatrice; Tesori, Valentina; Lattanzi, Wanda; Gasbarrini, Giovanni Battista; Gasbarrini, Antonio

    2013-05-28

    Tumors have long been viewed as a population in which all cells have the equal propensity to form new tumors, the so called conventional stochastic model. The cutting-edge theory on tumor origin and progression, tends to consider cancer as a stem cell disease. Stem cells are actively involved in the onset and maintenance of colon cancer. This review is intended to examine the state of the art on colon cancer stem cells (CSCs), with regard to the recent achievements of basic research and to the corresponding translational consequences. Specific prominence is given to the hypothesized origin of CSCs and to the methods for their identification. The growing understanding of CSC biology is driving the optimization of novel anti-cancer targeted drugs.

  15. Colon cancer: it's CIN or CIMP.

    PubMed

    Issa, Jean-Pierre

    2008-10-01

    Combined genetic and epigenetic analysis of sporadic colon cancer suggest that it can no longer be viewed as a single disease. There are at least three different subsets with distinct clinico-pathologic features, with important implications for preventions, screening, and therapy.

  16. The Value of Continuity between Primary Care and Surgical Care in Colon Cancer

    PubMed Central

    Hussain, Tanvir; Chang, Hsien-Yen; Luu, Ngoc-Phuong; Pollack, Craig Evan

    2016-01-01

    Background Improving continuity between primary care and cancer care is critical for improving cancer outcomes and curbing cancer costs. A dimension of continuity, we investigated how regularly patients receive their primary care and surgical care for colon cancer from the same hospital and whether this affects mortality and costs. Methods Using Surveillance, Epidemiology, and End Results Program Registry (SEER)-Medicare data, we performed a retrospective cohort study of stage I-III colon cancer patients diagnosed between 2000 and 2009. There were 23,305 stage I-III colon cancer patients who received primary care in the year prior to diagnosis and underwent operative care for colon cancer. Patients were assigned to the hospital where they had their surgery and to their primary care provider’s main hospital, and then classified according to whether these two hospitals were same or different. Outcomes examined were hazards for all-cause mortality, subhazard for colon cancer specific mortality, and generalized linear estimate for costs at 12 months, from propensity score matched models. Results Fifty-two percent of stage I-III colon patients received primary care and surgical care from the same hospital. Primary care and surgical care from the same hospital was not associated with reduced all-cause or colon cancer specific mortality, but was associated with lower inpatient, outpatient, and total costs of care. Total cost difference was $8,836 (95% CI $2,746–$14,577), a 20% reduction in total median cost of care at 12 months. Conclusions Receiving primary care and surgical care at the same hospital, compared to different hospitals, was associated with lower costs but still similar survival among stage I-III colon cancer patients. Nonetheless, health care policy which encourages further integration between primary care and cancer care in order to improve outcomes and decrease costs will need to address the significant proportion of patients receiving health care

  17. Patient Beliefs About Colon Cancer Screening.

    PubMed

    Ely, John W; Levy, Barcey T; Daly, Jeanette; Xu, Yinghui

    2016-03-01

    Only about half of eligible individuals undergo colon cancer screening. We have limited knowledge about the patient beliefs that adversely affect screening decisions and about which beliefs might be amenable to change through education. As part of a clinical trial, 641 rural Iowans, aged 52 to 79 years, reported their beliefs about colon cancer screening in response to a mailed questionnaire. Consenting subjects were randomized into four groups, which were distinguished by four levels of increasingly intensive efforts to promote screening. Two of the groups received mailed educational materials and completed a follow-up questionnaire, which allowed us to determine whether their beliefs about screening changed following the education. We also completed a factor analysis to identify underlying (latent) factors that might explain the responses to 33 questions about readiness, attitudes, and perceived barriers related to colon cancer screening. The strongest predictors of a patient's stated readiness to be screened were a physician's recommendation to be screened (1 point difference on 10-point Likert scale, 95 % confidence interval [CI], 0.5 to 1.6 point difference), a family history of colon cancer (0.85-point Likert scale difference, 95 % CI, 0.1 to 1.6), and a belief that health-care decisions should be mostly left to physicians rather than patients (Spearman correlation coefficient 0.21, P < .001). Of the 33 questionnaire items about screening beliefs, 11 (33 %) changed favorably following the educational intervention. In the factor analysis, the 33 items were reduced to 8 underlying factors, such as being too busy to undergo screening and worries about screening procedures. We found a limited number of underlying factors that may help explain patient resistance to colon cancer screening.

  18. Nuclear matrix proteins in human colon cancer.

    PubMed Central

    Keesee, S K; Meneghini, M D; Szaro, R P; Wu, Y J

    1994-01-01

    The nuclear matrix is the nonchromatin scaffolding of the nucleus. This structure confers nuclear shape, organizes chromatin, and appears to contain important regulatory proteins. Tissue specific nuclear matrix proteins have been found in the rat, mouse, and human. In this study we compared high-resolution two-dimensional gel electropherograms of nuclear matrix protein patterns found in human colon tumors with those from normal colon epithelia. Tumors were obtained from 18 patients undergoing partial colectomy for adenocarcinoma of the colon and compared with tissue from 10 normal colons. We have identified at least six proteins which were present in 18 of 18 colon tumors and 0 of 10 normal tissues, as well as four proteins present in 0 of 18 tumors and in 10 of 10 normal tissues. These data, which corroborate similar findings of cancer-specific nuclear matrix proteins in prostate and breast, suggest that nuclear matrix proteins may serve as important markers for at least some types of cancer. Images PMID:8127905

  19. Establishment of a cancer surveillance programme: the South African experience

    PubMed Central

    Singh, Elvira; Ruff, Paul; Babb, Chantal; Sengayi, Mazvita; Beery, Moira; Khoali, Lerato; Kellett, Patricia; Underwood, J Michael

    2015-01-01

    Cancer is projected to become a leading cause of morbidity and mortality in low-income and middle-income countries in the future. However, cancer incidence in South Africa is largely under-reported because of a lack of nationwide cancer surveillance networks. We describe present cancer surveillance activities in South Africa, and use the International Agency for Research on Cancer framework to propose the development of four population-based cancer registries in South Africa. These registries will represent the ethnic and geographical diversity of the country. We also provide an update on a cancer surveillance pilot programme in the Ekurhuleni Metropolitan District, and the successes and challenges in the implementation of the IARC framework in a local context. We examine the development of a comprehensive cancer surveillance system in a middle-income country, which might serve to assist other countries in establishing population-based cancer registries in a resource-constrained environment. PMID:26248849

  20. Symptoms Relevant to Surveillance for Ovarian Cancer

    PubMed Central

    Ore, Robert M.; Baldwin, Lauren; Woolum, Dylan; Elliott, Erika; Wijers, Christiaan; Chen, Chieh-Yu; Miller, Rachel W.; DeSimone, Christopher P.; Ueland, Frederick R.; Kryscio, Richard J.; van Nagell, John R.; Pavlik, Edward J.

    2017-01-01

    To examine how frequently and confidently healthy women report symptoms during surveillance for ovarian cancer. A symptoms questionnaire was administered to 24,526 women over multiple visits accounting for 70,734 reports. A query of reported confidence was included as a confidence score (CS). Chi square, McNemars test, ANOVA and multivariate analyses were performed. 17,623 women completed the symptoms questionnaire more than one time and >9500 women completed it more than one four times for >43,000 serially completed questionnaires. Reporting ovarian cancer symptoms was ~245 higher than ovarian cancer incidence. The positive predictive value (0.073%) for identifying ovarian cancer based on symptoms alone would predict one malignancy for 1368 cases taken to surgery due to reported symptoms. Confidence on the first questionnaire (83.3%) decreased to 74% when more than five questionnaires were completed. Age-related decreases in confidence were significant (p < 0.0001). Women reporting at least one symptom expressed more confidence (41,984/52,379 = 80.2%) than women reporting no symptoms (11,882/18,355 = 64.7%), p < 0.0001. Confidence was unrelated to history of hormone replacement therapy or abnormal ultrasound findings (p = 0.30 and 0.89). The frequency of symptoms relevant to ovarian cancer was much higher than the occurrence of ovarian cancer. Approximately 80.1% of women expressed confidence in what they reported. PMID:28335512

  1. Role of colonic stents in the management of colorectal cancers

    PubMed Central

    Sagar, Jayesh

    2016-01-01

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

  2. Modulation of colon cancer by nutmeg.

    PubMed

    Li, Fei; Yang, Xiu-Wei; Krausz, Kristopher W; Nichols, Robert G; Xu, Wei; Patterson, Andrew D; Gonzalez, Frank J

    2015-04-03

    Colon cancer is the most common cancer and the third leading cause of cancer mortality in humans. Using mass spectrometry-based metabolomics, the current study revealed the accumulation of four uremic toxins (cresol sulfate, cresol glucuronide, indoxyl sulfate, and phenyl sulfate) in the serum of mice harboring adenomatous polyposis coli (APC) gene mutation-induced colon cancer. These uremic toxins, likely generated from the gut microbiota, were associated with an increase in the expression of the proinflammatory cytokine IL-6 and a disorder of lipid metabolism. Nutmeg, which exhibits antimicrobial activity, attenuated the levels of uremic toxins and decreased intestinal tumorigenesis in Apc(min/+) mice. Nutmeg-treated Apc(min/+) mice had decreased IL-6 levels and normalized dysregulated lipid metabolism, suggesting that uremic toxins are responsible, in part, for the metabolic disorders that occur during tumorigenesis. These studies demonstrate a potential biochemical link among gut microbial metabolism, inflammation, and metabolic disorders and suggest that modulation of gut microbiota and lipid metabolism using dietary intervention or drugs may be effective in colon cancer chemoprevention strategies.

  3. Terahertz polarization imaging for colon cancer detection

    NASA Astrophysics Data System (ADS)

    Doradla, Pallavi; Alavi, Karim; Joseph, Cecil S.; Giles, Robert H.

    2014-03-01

    Continuous wave terahertz (THz) imaging has the potential to offer a safe, noninvasive medical imaging modality for delineating colorectal cancer. The terahertz reflectance measurements of fresh 3 - 5 mm thick human colonic excisions were acquired using a continuous-wave polarization imaging technique. A CO2 optically pumped Far- Infrared molecular gas laser operating at 584 GHz was used to illuminate the colon tissue, while the reflected signals were detected using a liquid Helium cooled silicon bolometer. Both co-polarized and cross-polarized remittance from the samples was collected using wire grid polarizers in the experiment. The experimental analysis of 2D images obtained from THz reflection polarization imaging techniques showed intrinsic contrast between cancerous and normal regions based on increased reflection from the tumor. Also, the study demonstrates that the cross-polarized terahertz images not only correlates better with the histology, but also provide consistent relative reflectance difference values between normal and cancerous regions for all the measured specimens.

  4. Coffee, colon function and colorectal cancer.

    PubMed

    Vitaglione, Paola; Fogliano, Vincenzo; Pellegrini, Nicoletta

    2012-09-01

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

  5. Burden of meticillin-resistant Staphylococcus aureus colonization and infection in London acute hospitals: retrospective on a voluntary surveillance programme.

    PubMed

    Mumtaz, S; Bishop, L A; Wright, A L; Kanfoudi, L; Duckworth, G; Fraser, G G

    2011-12-01

    Although meticillin-resistant Staphylococcus aureus (MRSA) is recognized as an important cause of hospital and community healthcare-associated morbidity, and colonization as a precursor to infection, few studies have attempted to assess the burden of both colonization and infection across acute healthcare providers within a defined health economy. This study describes the prevalence and incidence of MRSA colonization and infection in acute London hospital Trusts participating in a voluntary surveillance programme in 2000-2001. Hospital infection control staff completed a weekly return including details on incident and prevalent colonizations, bacteraemias and other significant infections due to MRSA. Incidence and prevalence rates were calculated for hospitals with sufficient participation across both years. Colonizations accounted for 79% of incident MRSA cases reported; 4% were bacteraemias, and 17% other significant infections. There was no change in incidence of colonization of hospital patients between 2000 and 2001. By contrast, there was an unexplained 49% increase in prevalence of colonizations over this period. For any given month, prevalent colonizations outnumbered incident colonizations at least twofold. This MRSA surveillance programme was unusual for prospective ascertainment of incident and prevalent cases of both colonization and infection within an English regional health economy. Consistent with other studies, the incidence and prevalence of colonization substantially exceeded infection. Given the small contribution of bacteraemias to the overall MRSA burden, and the surveillance, screening and control interventions of recent years, it may be appropriate to review the present reliance on bacteraemia surveillance.

  6. Guidelines for colonoscopy surveillance after cancer resection: a consensus update by the American Cancer Society and US Multi-Society Task Force on Colorectal Cancer.

    PubMed

    Rex, Douglas K; Kahi, Charles J; Levin, Bernard; Smith, Robert A; Bond, John H; Brooks, Durado; Burt, Randall W; Byers, Tim; Fletcher, Robert H; Hyman, Neil; Johnson, David; Kirk, Lynne; Lieberman, David A; Levin, Theodore R; O'Brien, Michael J; Simmang, Clifford; Thorson, Alan G; Winawer, Sidney J

    2006-01-01

    Patients with resected colorectal cancer are at risk for recurrent cancer and metachronous neoplasms in the colon. This joint update of guidelines by the American Cancer Society (ACS) and US Multi-Society Task Force on Colorectal Cancer addresses only the use of endoscopy in the surveillance of these patients. Patients with endoscopically resected Stage I colorectal cancer, surgically resected Stage II and III cancers, and Stage IV cancer resected for cure (isolated hepatic or pulmonary metastasis) are candidates for endoscopic surveillance. The colorectum should be carefully cleared of synchronous neoplasia in the perioperative period. In nonobstructed colons, colonoscopy should be performed preoperatively. In obstructed colons, double contrast barium enema or computed tomography colonography should be done preoperatively, and colonoscopy should be performed 3 to 6 months after surgery. These steps complete the process of clearing synchronous disease. After clearing for synchronous disease, another colonoscopy should be performed in 1 year to look for metachronous lesions. This recommendation is based on reports of a high incidence of apparently metachronous second cancers in the first 2 years after resection. If the examination at 1 year is normal, then the interval before the next subsequent examination should be 3 years. If that colonoscopy is normal, then the interval before the next subsequent examination should be 5 years. Shorter intervals may be indicated by associated adenoma findings (see Postpolypectomy Surveillance Guideline). Shorter intervals are also indicated if the patient's age, family history, or tumor testing indicate definite or probable hereditary nonpolyposis colorectal cancer. Patients undergoing low anterior resection of rectal cancer generally have higher rates of local cancer recurrence, compared with those with colon cancer. Although effectiveness is not proven, performance of endoscopic ultrasound or flexible sigmoidoscopy at 3- to 6

  7. Colon cancer: cancer stem cells markers, drug resistance and treatment.

    PubMed

    Kozovska, Zuzana; Gabrisova, Veronika; Kucerova, Lucia

    2014-10-01

    Malignant tumours consist of heterogeneous populations of tumour cells. Cancer stem cells (CSC) represent a population of cells within a tumour with highly tumorigenic and chemoresistant properties. These cells may be identified by the expression of CSC markers. There are several key stem cells markers specified for colon cancer: CD133, CD44, ALDH1, ALCAM. These days, a major obstacle to effective cancer management is development of a multidrug resistance (MDR). The principal mechanism responsible for development of MDR phenotype is the over-expression of ABC transporters. Tumours and relapsing tumours after therapy are drived by subpopulations of tumour cells with aggressive phenotype resistant to chemotherapeutics. These cells are called CSC or tumour-initiating cells (TIC). Here we outline recent information about MDR of colon cancer and CSC markers. We have focused on novel therapeutic strategies which have been developed to prevent or overcome MDR. One such strategy is a combination of chemotherapy and modulators of MDR pumps or chemotherapy and monoclonal antibodies against vascular endothelial growth factor VEGF. Colon cancer is characterized by the presence of colon CSC expressing specific stem cell markers. The divergent presence of these markers can help to adjust personalized therapy. The review provides a detailed overview of resistance of colon cancer cells and discusses how the presence of CSC markers can influence therapy and prognosis of patients.

  8. Racial/ethnic variation in the anatomic subsite location of in situ and invasive cancers of the colon.

    PubMed Central

    Shavers, Vickie L.

    2007-01-01

    INTRODUCTION: Approximately 145,000 Americans were diagnosed with colorectal cancer and 56,000 died from colorectal cancer in 2006. Although colorectal screening can reduce mortality and incidence, U.S. screening rates are particularly low for racial/ethnic minorities. Racial differences in the subsite location of colon cancers could have implications for colorectal screening. This study examines the anatomic subsite distribution of tumors among African-American, Hispanic, Asian-American/Pacific-Islander and non-Hispanic white (NHW) patients with colon cancer. METHODS: Surveillance and End Results program data for 254,469 primary in situ and invasive colon cancers for patients from 1973-2002 are included in this analysis. Descriptive analyses and logistic regression are used to describe and examine variations in the proportion of colon cancers diagnosed at sites proximal to the sigmoid colon or proximal to the splenic flexure over three successive time periods. RESULTS: The proportion of colon cancers diagnosed at the sigmoid colon was 15.6-21.3% lower, while diagnoses at the descending colon were 40.5.0-45.3.0% higher for African Americans than NHWs over the three time periods. In logistic regression analyses adjusted for gender, age group and year of diagnosis, the odds of a diagnosis of cancer proximal to the sigmoid colon or proximal to the splenic flexure was significantly higher for African Americans but lower for Hispanics and Asian Americans/Pacific Islanders compared to NHWs. DISCUSSION: The higher proportion of cancers among African Americans diagnosed at sites that are generally attempted but not always reached with a sigmoidscope suggest that African Americans may benefit from screening colonoscopy. They also highlight the need for systems that collect data that would allow a direct examination of the role that the differential use of specific colon screening tests and polypectomy play in racial/ethnic variation in colon cancer incidence and in the

  9. Human Colon Cancer Cells Cultivated in Space

    NASA Technical Reports Server (NTRS)

    1995-01-01

    Within five days, bioreactor cultivated human colon cancer cells (shown) grown in Microgravity on the STS-70 mission in 1995, had grown 30 times the volume of the control specimens on Earth. The samples grown in space had a higher level of cellular organization and specialization. Because they more closely resemble tumors found in the body, microgravity grown cell cultures are ideal for research purposes.

  10. Adjuvant treatment strategies for early colon cancer.

    PubMed

    Waterston, Ashita M; Cassidy, Jim

    2005-01-01

    Colon cancer remains a major cause of death; however, in the last 3 years a number of trials have been published that have led to changes in the treatment of patients with this disease. Initially, the adjuvant treatment of patients following curative resection was based on their Dukes staging; this is now being refined by consideration of other pathological factors, as well as the investigation of newer prognostic markers such as p53, Ki67 and a number of genes on chromosome 18. Tumours generally develop from the progressive accumulation of genetic events, although some develop through mutation or inactivation of DNA mismatch repair proteins leading to microsatellite instability; this is particularly important in Lynch's syndrome. The loss of gene expression can occur by deletion or mutation of genes or by aberrant methylation of CpG islands. In patients with Dukes C colon cancer the standard of care for adjuvant chemotherapy was previously based on bolus fluorouracil (5-fluorouracil) and folinic acid (leucovorin) administered 5 days per month or weekly for 6 months. Recent studies with a combination of infusional fluorouracil, folinic acid and oxaliplatin have been found to be superior. A further study replacing fluorouracil with oral capecitabine has also demonstrated equivalent disease-free survival. Although some debate remains regarding the benefit of adjuvant treatment for patients with Dukes B colon cancer, the emerging consensus is that, for those patients who are younger and have high-risk features, chemotherapy should be discussed. A number of large vaccine trials have also been conducted in the adjuvant setting and, overall, these have been disappointing. This is a rapidly advancing area of therapy and the results of new trials are awaited to determine whether additional benefits can be achieved with biological therapies such as anti-vascular endothelial growth factor and anti-epithelial growth factor receptor monoclonal antibodies, which have already

  11. Colon Cancer on The Rise Among Gen Xers, Millennials

    MedlinePlus

    ... Colon Cancer on the Rise Among Gen Xers, Millennials And an old adversary -- the obesity epidemic -- may ... their early 50s and younger -- Gen Xers and millennials -- are experiencing significant increases in colon and rectal ...

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

    PubMed

    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.

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

    PubMed Central

    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 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. PMID:26579381

  14. Colon adenoma features and their impact on risk of future advanced adenomas and colorectal cancer

    PubMed Central

    Calderwood, Audrey H; Lasser, Karen E; Roy, Hemant K

    2016-01-01

    AIM To review the evidence on the association between specific colon adenoma features and the risk of future colonic neoplasia [adenomas and colorectal cancer (CRC)]. METHODS We performed a literature search using the National Library of Medicine through PubMed from 1/1/2003 to 5/30/2015. Specific Medical Subject Headings terms (colon, colon polyps, adenomatous polyps, epidemiology, natural history, growth, cancer screening, colonoscopy, CRC) were used in conjunction with subject headings/key words (surveillance, adenoma surveillance, polypectomy surveillance, and serrated adenoma). We defined non-advanced adenomas as 1-2 adenomas each < 10 mm in size and advanced adenomas as any adenoma ≥ 10 mm size or with > 25% villous histology or high-grade dysplasia. A combined endpoint of advanced neoplasia included advanced adenomas and invasive CRC. RESULTS Our search strategy identified 592 candidate articles of which 8 met inclusion criteria and were relevant for assessment of histology (low grade vs high grade dysplasia, villous features) and adenoma size. Six of these studies met the accepted quality indicator threshold for overall adenoma detection rate > 25% among study patients. We found 254 articles of which 7 met inclusion criteria for the evaluation of multiple adenomas. Lastly, our search revealed 222 candidate articles of which 6 met inclusion criteria for evaluation of serrated polyps. Our review found that villous features, high grade dysplasia, larger adenoma size, and having ≥ 3 adenomas at baseline are associated with an increased risk of future colonic neoplasia in some but not all studies. Serrated polyps in the proximal colon are associated with an increased risk of future colonic neoplasia, comparable to having a baseline advanced adenoma. CONCLUSION Data on adenoma features and risk of future adenomas and CRC are compelling yet modest in absolute effect size. Future research should refine this risk stratification. PMID:28035253

  15. Cutaneous metastasis of colon cancer: case report and literature review.

    PubMed

    Sheets, Nicholas; Powers, Jeremy; Richmond, Bryan

    2014-01-01

    Cutaneous metastases arising from an internal malignancy are a rare phenomenon, occurring in 0.001% of all skin biopsies performed. Of these, 6.5% originate from the a primary colon cancer. Colon cancer, when metastatic to the skin, typically appears as a painless flesh-colored nodule or as a mass with occasional ulceration. We report a case of a large cutaneous metastasis to the suprascapular region as the initial presenting symptom of an underlying colon cancer.

  16. Akt Inhibitor MK2206 in Treating Patients With Previously Treated Colon or Rectal Cancer That is Metastatic or Locally Advanced and Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2016-12-13

    Colon Mucinous Adenocarcinoma; Colon Signet Ring Cell Adenocarcinoma; Rectal Mucinous Adenocarcinoma; Rectal Signet Ring Cell Adenocarcinoma; Recurrent Colon Carcinoma; Recurrent Rectal Carcinoma; 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

  17. Mucins and associated O-glycans based immunoprofile for stratification of colorectal polyps: clinical implication for improved colon surveillance

    PubMed Central

    Krishn, Shiv Ram; Kaur, Sukhwinder; Sheinin, Yuri M.; Smith, Lynette M.; Gautam, Shailendra K.; Patel, Asish; Jain, Maneesh; Juvvigunta, Vasthala; Pai, Priya; Lazenby, Audrey J.; Roy, Hemant K.; Batra, Surinder K.

    2017-01-01

    Sessile serrated adenoma/polyps (SSA/P) are premalignant lesions of colorectal cancer that are difficult to distinguish histologically from hyperplastic polyps (HP) of minimal to no malignant potential. Specific markers for differentiating SSA/P from HP can aid clinicians for optimizing colon surveillance intervals. The present study investigates the potential of mucins and associated O-glycans to distinguish SSA/P from HP. Expression of colonic mucins (MUC1, MUC4, MUC17, MUC2, and MUC5AC) and O-glycans [Sialyl LewisA (CA19-9) and Tn/Sialyl-Tn on MUC1] were analyzed in HP (n=33), SSA/P (n=39), and tubular adenoma (TA) (n=36) samples by immunohistochemistry. A significantly reduced expression of MUC4 (p=0.0066), elevated expression of MUC17 (p=0.0002), and MUC5AC (p<0.0001) was observed in SSA/P cases in comparison to HP cases. Interestingly, significantly higher number of SSA/P cases (p<0.0001) exhibited MUC5AC expression in the goblet cells as well as filled the crypt lumen compared to only goblet cells in majority of the HP cases. Improved diagnostic potential was revealed by multivariate logistic regression analysis where combinatorial panel of MUC5AC/MUC17 discriminated SSA/P from HP (SN/SP=85/82%). Finally, the decision tree model based marker panel (CA19-9/MUC17/MUC5AC) predicted HP, SSA/P and TA with SN/SP of 58%/95%, 79%/90% and 97%/83%, respectively. Overall, the mucin and associated O-glycan based panel defined in the present study could aid in discriminating SSA/P from HP to devise better colon surveillance strategies. PMID:27705923

  18. Cathelicidin suppresses colon cancer development by inhibition of cancer associated fibroblasts

    PubMed Central

    Cheng, Michelle; Ho, Samantha; Yoo, Jun Hwan; Tran, Deanna Hoang-Yen; Bakirtzi, Kyriaki; Su, Bowei; Tran, Diana Hoang-Ngoc; Kubota, Yuzu; Ichikawa, Ryan; Koon, Hon Wai

    2015-01-01

    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-β1-induced EMT of colon cancer cells. Media conditioned by the human colonic CCD-18Co fibroblasts promoted human colon cancer HT-29 cell proliferation. Cathelicidin pretreatment inhibited colon cancer cell proliferation mediated by media conditioned by human colonic CCD-18Co fibroblasts. Cathelicidin disrupted tubulin distribution in colonic fibroblasts. Disruption of tubulin in fibroblasts reduced fibroblast-supported colon cancer cell proliferation. Conclusion Cathelicidin effectively inhibits colon cancer development by interfering with EMT and fibroblast

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

    PubMed

    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.

  20. Is there a role for colon capsule endoscopy beyond colorectal cancer screening? A literature review.

    PubMed

    Triantafyllou, Konstantinos; Beintaris, Iosif; Dimitriadis, George D

    2014-09-28

    Colon capsule endoscopy is recommended in Europe alternatively to colonoscopy for colorectal cancer screening in average risk individuals. The procedure has also been proposed to complete colon examination in cases of incomplete colonoscopy or when colonoscopy is contraindicated or refused by the patient. As tissue samples cannot be obtained with the current capsule device, colon capsule endoscopy has no place in diagnosing ulcerative colitis or in dysplasia surveillance. Nevertheless, data are accumulating regarding its feasibility to examine ulcerative colitis disease extent and to monitor disease activity and mucosal healing, even though reported results on the capsule's performance in this field vary greatly. In this review we present the currently available evidence for the use of colon capsule endoscopy to complement colonoscopy failure to reach the cecum and its use to evaluate ulcerative colitis disease activity and extent. Moreover, we provide an outlook on issues requiring further investigation before the capsule becomes a mainstream alternative to colonoscopy in such cases.

  1. Colon cancer presenting as a testicular metastasis

    PubMed Central

    Mohiuddin, Majid; Sharif, Asma

    2016-01-01

    We report a case of a 43-year-old male who initially presented with intermittent testicular pain as the first sign of metastatic stage IV colon cancer. Physical examination revealed a normal penis, scrotum and testes. Magnetic resonance imaging (MRI) of pelvis showed an irregular 3 cm mass of the spermatic cord and right radical inguinal orchiectomy was performed. The pathological diagnosis was metastatic adenocarcinoma. In conclusion, even though metastases to the testes are rare, they should be considered in clinical practice especially in older men who present with a testicular mass or discomfort. PMID:28138654

  2. Current treatment options for colon cancer peritoneal carcinomatosis

    PubMed Central

    Aoyagi, Tomoyoshi; Terracina, Krista P; Raza, Ali; Takabe, Kazuaki

    2014-01-01

    Peritoneal carcinomatosis (PC), the dissemination of cancer cells throughout the lining of the abdominal cavity, is the second most common presentation of colon cancer distant metastasis. Despite remarkable advances in cytotoxic chemotherapy and targeted therapy for colon cancer over the last 15 years, it has been repeatedly shown that these therapies remain ineffective for colon cancer PC. Recently, there has been a rapid accumulation of reports that cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) prolongs the life of colon cancer PC patients. Here, we will review the clinical presentation, the mechanisms of disease progression, and current treatment options for colon cancer PC, with a focus on the benefits and limitations of CRS-HIPEC. PMID:25253949

  3. Current treatment options for colon cancer peritoneal carcinomatosis.

    PubMed

    Aoyagi, Tomoyoshi; Terracina, Krista P; Raza, Ali; Takabe, Kazuaki

    2014-09-21

    Peritoneal carcinomatosis (PC), the dissemination of cancer cells throughout the lining of the abdominal cavity, is the second most common presentation of colon cancer distant metastasis. Despite remarkable advances in cytotoxic chemotherapy and targeted therapy for colon cancer over the last 15 years, it has been repeatedly shown that these therapies remain ineffective for colon cancer PC. Recently, there has been a rapid accumulation of reports that cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) prolongs the life of colon cancer PC patients. Here, we will review the clinical presentation, the mechanisms of disease progression, and current treatment options for colon cancer PC, with a focus on the benefits and limitations of CRS-HIPEC.

  4. Oxaliplatin and Infliximab Combination Synergizes in Inducing Colon Cancer Regression

    PubMed Central

    Li, Wenya; Xu, Jian; Zhao, Jian; Zhang, Rui

    2017-01-01

    Background Colon cancer is one of the most common malignant cancers and causes millions of deaths each year. There are still no effective treatments for colon cancer patients who are at advanced stage. Tumor necrosis factor-alpha (TNF-α) might be a good therapy target due to its widely-accepted roles in regulating multiple important biological processes, especially in promoting inflammation. Material/Methods We evaluated the expression of TNF-α in 108 human colon cancer tissue samples and 2 colon cancer cell lines (CT26 and HCT116), and analyzed its prognostic values. Further, we explored the roles and mechanism of anti-TNF-α treatment in combination with chemotherapy in vitro and in vivo. Results We found that TNF-α was highly expressed in colon cancer cell lines. The survival analysis and Cox regression analysis indicated that high TNF-α was an independent adverse prognosticator of colon cancer. In addition, anti-TNF-α treatment enhanced the effects of chemotherapy in the xenograft mouse model through inducing ADCC and CDC effects. Conclusions We conclude that TNF-α is an independent adverse prognosticator of colon cancer, and anti-TNF-α might benefit colon cancer patients. PMID:28190020

  5. Microchimerism and survival after breast and colon cancer diagnosis.

    PubMed

    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 addendum, I report the survival of cases in the original study after being diagnosed with cancer. Despite small numbers, the analysis suggests that microchimerism may be positively associated with survival after breast and maybe colon cancer diagnosis. Despite the findings on colon cancer in our original report, I speculate whether microchimerism could have a general beneficial role in cancer, which in some sites may not be evident because an allogeneic maternal immune reaction hastens cancer development.

  6. Surveillance and Care of the Gynecologic Cancer Survivor

    PubMed Central

    MacLaughlin, Kathy L.; Long, Margaret E.; Pruthi, Sandhya; Casey, Petra M.

    2015-01-01

    Abstract Background: Care of the gynecologic cancer survivor extends beyond cancer treatment to encompass promotion of sexual, cardiovascular, bone, and brain health; management of fertility, contraception, and vasomotor symptoms; and genetic counseling. Methods: This is a narrative review of the data and guidelines regarding care and surveillance of the gynecologic cancer survivor. We searched databases including PubMed, Cochrane, and Scopus using the search terms gynecologic cancer, cancer surveillance, and cancer survivor and reached a consensus for articles chosen for inclusion in the review based on availability in the English language and publication since 2001, as well as key older articles, consensus statements, and practice guidelines from professional societies. However, we did not undertake an extensive systematic search of the literature to identify all potentially relevant studies, nor did we utilize statistical methods to summarize data. We offer clinical recommendations for the management of gynecologic cancer survivors based on review of evidence and our collective clinical experience. Results: Key messages include the limitations of laboratory studies, including CA-125, and imaging in the setting of gynecologic cancer surveillance, hormonal and non-hormonal management of treatment-related vasomotor symptoms and genitourinary syndrome of menopause, as well as recommendations for general health screening, fertility preservation, and contraception. Conclusions: A holistic approach to care extending beyond cancer treatment alone benefits gynecologic cancer survivors. In addition to surveillance for cancer recurrence and late treatment side effects, survivors benefit from guidance on hormonal, contraceptive, and fertility management and promotion of cardiovascular, bone, brain, and sexual health. PMID:26208166

  7. [Colon cancer after colon interposition for oesophageal replacement].

    PubMed

    Sikorszki, László; Horváth, Ors Péter; Papp, András; Cseke, László; Pavlovics, Gábor

    2010-08-01

    The authors report the case of a colon adenocarcinoma developed on the neck at the anastomosis of the skin tube and colon 44 years following a corrosive oesophageal injury. This patient suffered a moderately severe oesophageal, stomach and laryngeal injuries due to drinking hydrochloric acid 44 years ago. He underwent serial laryngoplasties, then needed a tracheostomy, oesophagectomy, pyloroplasty and ileocolon transposition. An antethoracal oesophagus formation was performed with ileocolon and skin tube amendment. 44 years later an ulcerated adenocarcinoma developed in the transposed colon, which was resected and the ability to swallow was reinstated by the transplantation of an isolated jejunal segment using microvascular anastomosis.

  8. LIN28B Promotes Colon Cancer Migration and Recurrence

    PubMed Central

    Pang, Minghui; Wu, Gang; Hou, Xiaolin; Hou, Nengyi; Liang, Liqin; Jia, Guiqing; Shuai, Ping; Luo, Bin; Wang, Kang; Li, Guoxin

    2014-01-01

    LIN28B is involved in “stemness” and tumourigenesis by negatively regulating the maturation of let-7 microRNA family members. In this study, we showed that LIN28B expression promotes migration and recurrence of colon cancer. Immunohistochemistry and reverse-transcription polymerase chain reactions were performed to detect LIN28B expression in colon cancer tissue microarrays, paraffin-embedded surgical resected tissues and cancer cells. Loss-of-function, migration and proliferation analyses were performed to delineate the potential roles of LIN28B in colon cancer. LIN28B was upregulated in colon cancer tissue compared to normal mucosa, and its overexpression correlated with reduced patient survival and increased tumour recurrence. LIN28B suppression inhibited the migration of SW480 colon cancer cells and facilitated the cytotoxicity induced by oxaliplatin in SW480 and HCT116 colon cancer cells. In conclusion, LIN28B overexpression contributes to colon tumourigenesis, and LIN28B may serve as a diagnostic tool and therapeutic target for colon cancer. PMID:25360631

  9. DNA testing and molecular screening for colon cancer.

    PubMed

    Carethers, John M

    2014-03-01

    Colon cancer develops and progresses as a consequence of abnormal cellular molecular changes, many of which result in mutant DNA. Modern molecular techniques allow examination of individual patient genetic data that ascribe risk, predict outcome, and/or modify an approach to therapy. DNA testing and molecular screening are in use today and are becoming a critical and necessary part of routine patient care. Assessing at-risk patients for hereditary colon cancer is predicted to move from individual gene testing that is commonly performed today to whole exome or whole genome sequencing, providing additional vast information of the patient's genome that might not be related to the colon cancer syndrome. Detecting mutant DNA from shed tumor cells in fecal material for colon cancer screening will increase in diagnostic accuracy over time, with improvements in the panel of mutant DNA being examined and through clinical testing. DNA mutations and other molecular changes detected directly from within the colon cancer help to inform and guide the physician for the best approach for optimal patient care and outcome. The use of epidermal growth factor receptor-targeted therapy in advanced colon cancer patients requires knowledge of the mutation status for KRAS and BRAF genes, and knowing the mutational status of PIK3CA may predict how patients respond to aspirin to prevent colon cancer recurrence. Biologically driven decision-making, or precision medicine, is becoming increasingly adopted for optimal care and outcome for colon cancer patients. Gastroenterologists will need to be increasingly aware.

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

    PubMed

    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.

  11. Proteoglycans as potential microenvironmental biomarkers for colon cancer.

    PubMed

    Suhovskih, Anastasia V; Aidagulova, Svetlana V; Kashuba, Vladimir I; Grigorieva, Elvira V

    2015-09-01

    Glycosylation changes occur widely in colon tumours, suggesting glycosylated molecules as potential biomarkers for colon cancer diagnostics. In this study, proteoglycans (PGs) expression levels and their transcriptional patterns are investigated in human colon tumours in vivo and carcinoma cells in vitro. According to RT-PCR analysis, normal and cancer colon tissues expressed a specific set of PGs (syndecan-1, perlecan, decorin, biglycan, versican, NG2/CSPG4, serglycin, lumican, CD44), while the expression of glypican-1, brevican and aggrecan was almost undetectable. Overall transcriptional activity of the PGs in normal and cancer tissues was similar, although expression patterns were different. Expression of decorin and perlecan was down-regulated 2-fold in colon tumours, while biglycan and versican expression was significantly up-regulated (6-fold and 3-fold, respectively). Expression of collagen1A1 was also increased 6-fold in colon tumours. However, conventional HCT-116 colon carcinoma and AG2 colon cancer-initiating cells did not express biglycan and decorin and were versican-positive and -negative, respectively, demonstrating an extracellular origin of the PGs in cancer tissue. Selective expression of heparan sulfate (HS) proteoglycans syndecan-1 and perlecan in the AG2 colon cancer-initiating cell line suggests these PGs as potential biomarkers for cancer stem cells. Overall transcriptional activity of the HS biosynthetic system was similar in normal and cancer tissues, although significant up-regulation of extracellular sulfatases SULF1/2 argues for a possible distortion of HS sulfation patterns in colon tumours. Taken together, the obtained results suggest versican, biglycan, collagen1A1 and SULF1/2 expression as potential microenvironmental biomarkers and/or targets for colon cancer diagnostics and treatment.

  12. The association of percentage energy from fat and colon cancer risk among members of the U.S. military

    PubMed Central

    Shao, Stephanie; Kao, Tzu-Cheg; Eckhaus, Janet; Bourgeois, Jolie; Perera, Kanchana; Zhu, Kangmin

    2014-01-01

    Purpose Epidemiologic studies have previously reported an association between high fat intake and colon cancer risk. However, findings have generally been inconclusive. This study aimed to investigate the association between fat as a percentage of energy intake and colon cancer risk. Methods Study subjects included 215 cases and 215 matched controls identified by the Defense Medical Surveillance System. Percentage energy from fat (Pfat) was estimated using a short dietary screener developed by the National Cancer Institute for two time periods: the year before first blood draw and colon cancer diagnosis. Conditional logistic regression analysis was used to assess the relationship between colon cancer risk and Pfat. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Results Compared with the lowest quartile of Pfat, the adjusted odds of having colon cancer were 2.00 (95% CI 0.96–4.18), 2.83 (95% CI 1.41–5.66) and 3.37 (95% CI 1.58–7.17) for the second, third, and highest quartiles in the year before cancer diagnosis. Similar results were observed for Pfat at an earlier time. Conclusion Our findings suggest a positive association between Pfat and colon cancer in the U.S. military population. PMID:25075879

  13. The association of percentage energy from fat and colon cancer risk among members of the US military.

    PubMed

    Shao, Stephanie; Kao, Tzu-Cheg; Eckhaus, Janet; Bourgeois, Jolie; Perera, Kanchana; Zhu, Kangmin

    2015-05-01

    Epidemiologic studies have previously reported an association between high fat intake and colon cancer risk. However, findings have generally been inconclusive. This study aimed to investigate the association between fat as a percentage of energy intake and colon cancer risk. Study subjects included 215 cases and 215 matched controls identified by the Defense Medical Surveillance System. Percentage energy from fat (Pfat) was estimated using a short dietary screener developed by the National Cancer Institute for two time periods: the year before the first blood draw and the year before colon cancer diagnosis. Conditional logistic regression analysis was used to assess the relationship between colon cancer risk and Pfat. Odds ratios and 95% confidence intervals (CIs) were calculated. Compared with the lowest quartile of Pfat, the adjusted odds of having colon cancer were 2.00 (95% CI 0.96-4.18), 2.83 (95% CI 1.41-5.66), and 3.37 (95% CI 1.58-7.17), respectively, for the second, third, and highest quartiles in the year before cancer diagnosis. Similar results were observed for Pfat at an earlier time point. Our findings suggest a positive association between Pfat and colon cancer in the US military population.

  14. VEGF and colon cancer growth beyond angiogenesis: does VEGF directly mediate colon cancer growth via a non-angiogenic mechanism?

    PubMed

    Ahluwalia, Amrita; Jones, Michael K; Matysiak-Budnik, Tamara; Tarnawski, Andrzej S

    2014-01-01

    In this article we review the role of vascular endothelial growth factor (VEGF) in colon cancer growth and the underlying mechanisms. Angiogenesis, the growth of new capillary blood vessels in the body, is critical for tissue injury healing and cancer growth. In 1971, Judah Folkman proposed the concept that tumor growth beyond 2 mm is critically dependent on angiogenesis. Tumors including colon cancers release angiogenic growth factors that stimulate blood vessels to grow into the tumors thus providing oxygen and nutrients that enable exponential growth. VEGF is the most potent angiogenic growth factor. Several studies have highlighted the role of VEGF in colon cancer, specifically in the stimulation of angiogenesis. This role of VEGF is strongly supported by studies showing that inhibition of VEGF using the blocking antibody, bevacizumab, results in decreased angiogenesis and abrogation of cancer growth. In the United States, bevacizumab in combination with chemotherapy is FDA approved for the treatment of metastatic colon cancer. However, the source of VEGF in colon cancer tissue, the mechanisms of VEGF generation in colon cancer cells and the molecular pathways involved in VEGF mediated angiogenesis in colon cancer are not fully known. The possibility that VEGF directly stimulates cancer cell growth in an autocrine manner has not been explored in depth.

  15. Guidelines for colonoscopy surveillance after cancer resection: a consensus update by the American Cancer Society and the US Multi-Society Task Force on Colorectal Cancer.

    PubMed

    Rex, Douglas K; Kahi, Charles J; Levin, Bernard; Smith, Robert A; Bond, John H; Brooks, Durado; Burt, Randall W; Byers, Tim; Fletcher, Robert H; Hyman, Neil; Johnson, David; Kirk, Lynne; Lieberman, David A; Levin, Theodore R; O'Brien, Michael J; Simmang, Clifford; Thorson, Alan G; Winawer, Sidney J

    2006-05-01

    Patients with resected colorectal cancer are at risk for recurrent cancer and metachronous neoplasms in the colon. This joint update of guidelines by the American Cancer Society and the US Multi-Society Task Force on Colorectal Cancer addresses only the use of endoscopy in the surveillance of these patients. Patients with endoscopically resected Stage I colorectal cancer, surgically resected Stages II and III cancers, and Stage IV cancer resected for cure (isolated hepatic or pulmonary metastasis) are candidates for endoscopic surveillance. The colorectum should be carefully cleared of synchronous neoplasia in the perioperative period. In nonobstructed colons, colonoscopy should be performed preoperatively. In obstructed colons, double-contrast barium enema or computed tomography colonography should be performed preoperatively, and colonoscopy should be performed 3 to 6 months after surgery. These steps complete the process of clearing synchronous disease. After clearing for synchronous disease, another colonoscopy should be performed in 1 year to look for metachronous lesions. This recommendation is based on reports of a high incidence of apparently metachronous second cancers in the first 2 years after resection. If the examination at 1 year is normal, then the interval before the next subsequent examination should be 3 years. If that examination is normal, then the interval before the next subsequent examination should be 5 years. Shorter intervals may be indicated by associated adenoma findings (see "Guidelines for Colonoscopy Surveillance After Polypectomy: A Consensus Update by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society"). Shorter intervals also are indicated if the patient's age, family history, or tumor testing indicate definite or probable hereditary nonpolyposis colorectal cancer. Patients undergoing low anterior resection of rectal cancer generally have higher rates of local cancer recurrence compared with those

  16. Vertebral Metastasis as the Initial Manifestation of Colon Cancer

    PubMed Central

    Jain, Tushina; Williams, Renee; Liechty, Benjamin

    2016-01-01

    Oncology guidelines currently recommend against performing colonoscopies in the workup of adenocarcinoma of unknown primary unless colonic malignancy is otherwise suggested by clinical signs or symptoms. We present 2 cases of metastatic colonic adenocarcinoma that presented only with neurologic symptoms from vertebral metastasis. Although bony metastases are a rare presentation of colon cancer and colonoscopy is not warranted in the initial workup of adenocarcinoma of unknown primary, we describe these cases as a reminder that bony metastases do not rule out a colon cancer diagnosis. PMID:27807574

  17. Vertebral Metastasis as the Initial Manifestation of Colon Cancer.

    PubMed

    Jain, Tushina; Williams, Renee; Liechty, Benjamin; Ann Chen, Lea

    2016-08-01

    Oncology guidelines currently recommend against performing colonoscopies in the workup of adenocarcinoma of unknown primary unless colonic malignancy is otherwise suggested by clinical signs or symptoms. We present 2 cases of metastatic colonic adenocarcinoma that presented only with neurologic symptoms from vertebral metastasis. Although bony metastases are a rare presentation of colon cancer and colonoscopy is not warranted in the initial workup of adenocarcinoma of unknown primary, we describe these cases as a reminder that bony metastases do not rule out a colon cancer diagnosis.

  18. The rationale for patient-reported outcomes surveillance in cancer and a reproducible method for achieving it.

    PubMed

    Smith, Tenbroeck G; Castro, Kathleen M; Troeschel, Alyssa N; Arora, Neeraj K; Lipscomb, Joseph; Jones, Shelton M; Treiman, Katherine A; Hobbs, Connie; McCabe, Ryan M; Clauser, Steven B

    2016-02-01

    Patient-reported outcomes (PROs) measure quality of life, symptoms, patient functioning, and patient perceptions of care; they are essential for gaining a full understanding of cancer care and the impact of cancer on people's lives. Repeatedly captured facility-level and/or population-level PROs (PRO surveillance) could play an important role in quality monitoring and improvement, benchmarking, advocacy, policy making, and research. This article describes the rationale for PRO surveillance and the methods of the Patient Reported Outcomes Symptoms and Side Effects Study (PROSSES), which is the first PRO study to use the American College of Surgeons Commission on Cancer's Rapid Quality Reporting System to identify patients and manage study data flow. The American Cancer Society, the National Cancer Institute, the Commission on Cancer, and RTI International collaborated on PROSSES. PROSSES was conducted at 17 cancer programs that participated in the National Cancer Institute Community Cancer Centers Program among patients diagnosed with locoregional breast or colon cancer. The methods piloted in PROSSES were successful as demonstrated by high eligibility (93%) and response (61%) rates. Differences in clinical and demographic characteristics between respondents and nonrespondents were mostly negligible, with the exception that non-white individuals were somewhat less likely to respond. These methods were consistent across cancer centers and reproducible over time. If repeated and expanded, they could provide PRO surveillance data from patients with cancer on a national scale.

  19. Chemopreventive effect of apple and berry fruits against colon cancer.

    PubMed

    Jaganathan, Saravana Kumar; Vellayappan, Muthu Vignesh; Narasimhan, Gayathri; Supriyanto, Eko; Octorina Dewi, Dyah Ekashanti; Narayanan, Aqilah Leela T; Balaji, Arunpandian; Subramanian, Aruna Priyadarshini; Yusof, Mustafa

    2014-12-07

    Colon cancer arises due to the conversion of precancerous polyps (benign) found in the inner lining of the colon. Prevention is better than cure, and this is very true with respect to colon cancer. Various epidemiologic studies have linked colorectal cancer with food intake. Apple and berry juices are widely consumed among various ethnicities because of their nutritious values. In this review article, chemopreventive effects of these fruit juices against colon cancer are discussed. Studies dealing with bioavailability, in vitro and in vivo effects of apple and berry juices are emphasized in this article. A thorough literature survey indicated that various phenolic phytochemicals present in these fruit juices have the innate potential to inhibit colon cancer cell lines. This review proposes the need for more preclinical evidence for the effects of fruit juices against different colon cancer cells, and also strives to facilitate clinical studies using these juices in humans in large trials. The conclusion of the review is that these apple and berry juices will be possible candidates in the campaign against colon cancer.

  20. Chemopreventive effect of apple and berry fruits against colon cancer

    PubMed Central

    Jaganathan, Saravana Kumar; Vellayappan, Muthu Vignesh; Narasimhan, Gayathri; Supriyanto, Eko; Octorina Dewi, Dyah Ekashanti; Narayanan, Aqilah Leela T; Balaji, Arunpandian; Subramanian, Aruna Priyadarshini; Yusof, Mustafa

    2014-01-01

    Colon cancer arises due to the conversion of precancerous polyps (benign) found in the inner lining of the colon. Prevention is better than cure, and this is very true with respect to colon cancer. Various epidemiologic studies have linked colorectal cancer with food intake. Apple and berry juices are widely consumed among various ethnicities because of their nutritious values. In this review article, chemopreventive effects of these fruit juices against colon cancer are discussed. Studies dealing with bioavailability, in vitro and in vivo effects of apple and berry juices are emphasized in this article. A thorough literature survey indicated that various phenolic phytochemicals present in these fruit juices have the innate potential to inhibit colon cancer cell lines. This review proposes the need for more preclinical evidence for the effects of fruit juices against different colon cancer cells, and also strives to facilitate clinical studies using these juices in humans in large trials. The conclusion of the review is that these apple and berry juices will be possible candidates in the campaign against colon cancer. PMID:25493015

  1. Colon cancer presented with sigmoid volvulus: A case report

    PubMed Central

    Aras, Abbas; Kızıltan, Remzi; Batur, Abdussamet; Çelik, Sebahattin; Yılmaz, Özkan; Kotan, Çetin

    2015-01-01

    Introduction Sigmoid volvulus is the most prevalent type of colonic volvulus. Colon cancer is seen less where sigmoid volvulus is common, so it is rare to see that colon cancer is synchronous with sigmoid volvulus. Presentation of case We would like to present a case of sigmoid volvulus caused by colon cancer in a male patient aged 80 who was referred to the hospital with toxaemic shock presentation. Discussion Sigmoid cancer can be presented as sigmoid volvulus to the emergency department. In intestinal obstruction early diagnosis is of crucial importance. Computarized tomography is a diagnosis tool that should be preferred both in the diagnosis of obstruction and in detecting its cause, localisation, degree and complications. Conclusion When surgery is performed due to the urgent colonic obstruction in colonic volvulus diagnosed patients, a colon tumour should be considered in the same column loops or in the distal colon. We believe that CT is the method that should be preferred in large-bowel obstruction suspected patients. PMID:26519810

  2. Hereditary diffuse gastric cancer: surgery, surveillance and unanswered questions.

    PubMed

    Cisco, Robin M; Norton, Jeffrey A

    2008-08-01

    Hereditary diffuse gastric cancer (HDGC) is an inherited cancer-susceptibility syndrome characterized by autosomal dominance and high penetrance. In 30-50% of cases, a causative germline mutation in CDH1, the E-cadherin gene, may be identified. Female carriers of CDH1 mutations also have an increased (20-40%) risk of lobular breast cancer. Endoscopic surveillance of patients with CDH1 mutations is ineffective because early foci of HDGC are typically small and underlie normal mucosa. CDH1 mutation carriers are therefore offered the option of prophylactic gastrectomy, which commonly reveals early foci of invasive signet-ring cell cancer. We review recommendations for genetic testing, surveillance and prophylactic surgery in HDGC. Areas for future research are discussed, including development of new screening modalities, optimal timing of prophylactic gastrectomy, identification of additional causative mutations in HDGC, management of patients with CDH1 missense mutations and prevention/early detection of lobular breast cancer in CDH1 mutation carriers.

  3. Collaborative Model for Acceleration of Individualized Therapy of Colon Cancer

    DTIC Science & Technology

    2014-10-01

    ORGANIZATION NAME(S) AND ADDRESS(ES) COLORADO , DENVER 8. PERFORMING ORGANIZATION REPORT NUMBER...Individualized Therapy of Colon Cancer PRINCIPAL INVESTIGATOR: Aik Choon Tan, Ph.D. CONTRACTING ORGANIZATION: UNIVERSITY OF COLORADO

  4. Gut Bacteria May Link Diet, Colon Cancer, Study Says

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_163274.html Gut Bacteria May Link Diet, Colon Cancer, Study Says High- ... link appears to be a type of intestinal bacteria, the Boston research team said. Specifically, they looked ...

  5. Colon Cancer Rates, Deaths Drop in Americans Over 50

    MedlinePlus

    ... gov/news/fullstory_163856.html Colon Cancer Rates, Deaths Drop in Americans Over 50 Report suggests higher ... over 50 fell 32 percent since 2000, while deaths from the disease fell by 34 percent. Those ...

  6. Vitamin E, Selenium Don't Cut Colon Cancer Risk

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_162669.html Vitamin E, Selenium Don't Cut Colon Cancer Risk: ... 2016 WEDNESDAY, Dec. 21, 2016 (HealthDay News) -- Taking vitamin E and selenium does not appear to reduce ...

  7. Patients with Acromegaly Presenting with Colon Cancer: A Case Series

    PubMed Central

    Nakhle, Samer; Ludlam, William H.

    2016-01-01

    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. PMID:28025627

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

    ClinicalTrials.gov

    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

  9. Impact of national guidelines on family history breast cancer surveillance.

    PubMed

    Saldanha, J D; Garrett, R M; Snaddon, L; Longmuir, M; Bradshaw, N; Watt, C; George, W D; Wilson, C R; Doughty, J C; Stallard, S; Reid, I; Murday, V; Davidson, R

    2011-11-01

    The breast cancer risk of women already under family history surveillance was accurately assessed according to national guidelines in an attempt to rationalize the service. Women attending two breast units in Glasgow between November 2003 and February 2005 were included. One thousand and five women under annual surveillance were assessed and had their relatives diagnoses verified. Four hundred and ninety-seven women were at significantly increased risk and eligible for follow-up. Five hundred and eight (50%) women attending were not eligible for family history surveillance, and 498 (98%) of these women accepted discharge. In conclusion, national guidelines have helped to more clearly define women who should undergo surveillance. This avoids unnecessary and potentially harmful routine investigations, and the service has been improved.

  10. Irinotecan-Eluting Beads in Treating Patients With Refractory Metastatic Colon or Rectal Cancer That Has Spread to the Liver

    ClinicalTrials.gov

    2017-01-24

    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 IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

  11. Idelalisib induces PUMA-dependent apoptosis in colon cancer cells

    PubMed Central

    Yang, Shida; Zhu, Zhiyong; Zhang, Xiaobing; Zhang, Ning; Yao, Zhicheng

    2017-01-01

    Idelalisib, a PI3K inhibitor, specifically targeting p110δ, has been approved for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma and follicular lymphoma. However, the mechanisms of action of idelalisib in colon cancer cells are not well understood. We investigated how idelalisib suppresses colon cancer cells growth and potentiates effects of other chemotherapeutic drugs. In this study, we found that idelalisib treatment induces PUMA in colon cancer cells irrespective of p53 status through the p65 pathway following AKT inhibition and glycogen synthase kinase 3β (GSK3β) activation. PUMA is necessary for idelalisib-induced apoptosis in colon cancer cells. Idelalisib also synergized with 5-FU or regorafenib to induce marked apoptosis via PUMA in colon cancer cells. Furthermore, PUMA deficiency suppressed apoptosis and antitumor effect of idelalisib in xenograft model. These results demonstrate a critical role of PUMA in mediating the anticancer effects of idelalisib in colon cancer cells and suggest that PUMA induction can be used as an indicator of idelalisib sensitivity, and also have important implications for it clinical applications. PMID:28008149

  12. Idelalisib induces PUMA-dependent apoptosis in colon cancer cells.

    PubMed

    Yang, Shida; Zhu, Zhiyong; Zhang, Xiaobing; Zhang, Ning; Yao, Zhicheng

    2017-01-24

    Idelalisib, a PI3K inhibitor, specifically targeting p110δ, has been approved for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma and follicular lymphoma. However, the mechanisms of action of idelalisib in colon cancer cells are not well understood. We investigated how idelalisib suppresses colon cancer cells growth and potentiates effects of other chemotherapeutic drugs. In this study, we found that idelalisib treatment induces PUMA in colon cancer cells irrespective of p53 status through the p65 pathway following AKT inhibition and glycogen synthase kinase 3β (GSK3β) activation. PUMA is necessary for idelalisib-induced apoptosis in colon cancer cells. Idelalisib also synergized with 5-FU or regorafenib to induce marked apoptosis via PUMA in colon cancer cells. Furthermore, PUMA deficiency suppressed apoptosis and antitumor effect of idelalisib in xenograft model. These results demonstrate a critical role of PUMA in mediating the anticancer effects of idelalisib in colon cancer cells and suggest that PUMA induction can be used as an indicator of idelalisib sensitivity, and also have important implications for it clinical applications.

  13. Natural products and colon cancer: current status and future prospects

    PubMed Central

    Rajamanickam, Subapriya; Agarwal, Rajesh

    2008-01-01

    Carcinogenesis is a multistage process consisting of initiation, promotion and progression phases. Thus, the multistage sequence of events has many phases for prevention and intervention. Chemoprevention, a novel approach for controlling cancer, involves the use of specific natural products or synthetic chemical agents to reverse, suppress or prevent premalignancy before the development of invasive cancer. Several natural products, such as, grains, nuts, cereals, spices, fruits, vegetables, beverages, medicinal plants and herbs and their various phytochemical constituents including, phenolics, flavonoids, carotenoids, alkaloids, nitrogen containing as well as organosulfur compounds confer protective effects against wide range of cancers including colon cancer. Since diet has an important role in the etiology of colon cancer, dietary chemoprevention received attention for colon cancer prevention. However, identification of an agent with chemopreventive potential requires in vitro studies, efficacy and toxicity studies in animal models before embarking on human clinical trials. A brief introduction about colon cancer and the role of some recent natural products in colon cancer chemoprevention with respect to multiple molecular mechanisms in various in vitro, in vivo and clinical studies are described in this review. PMID:19884979

  14. Cancer surveillance of patients with longstanding ulcerative colitis: a clinical, endoscopical, and histological study.

    PubMed Central

    Broström, O; Löfberg, R; Ost, A; Reichard, H

    1986-01-01

    An eight year endoscopical and histological cancer surveillance programme comprising 71 patients with ulcerative colitis is presented. Forty one patients had total colitis and 30 substantial colitis. Mean duration of the disease was 19.7 years (range 9-46 years). An average of 2.6 colonoscopies per patient in the total colitis group were carried out, and at least two biopsies were taken at 10 locations in the colon. In the total colitis group, seven had either low (four), or high grade dysplasia (two), or Dukes' A cancer (one). In the group with substantial colitis two patients with low grade dysplasia were found. Dysplasia or cancer leading to operation was found above the rectum in four of five operated patients, all having had total colitis for 25 to 44 years. The dysplasia and cancer findings at the colonoscopy preceding surgery corresponded well with the surgical specimens. In three operated patients a sequence of dysplasia development was recorded. With the exception of long duration and dysplasia, nothing in the clinical course distinguished the operated cases. Using this surveillance programme prophylactic colectomy can be limited to patients in a high risk group developing dysplasia. The risk of missing a cancer before it becomes incurable seems to be low. PMID:3804019

  15. Metformin: A Potential Therapeutic Agent for Recurrent Colon Cancer

    PubMed Central

    Nangia-Makker, Pratima; Yu, Yingjie; Vasudevan, Anita; Farhana, Lulu; Rajendra, Sindhu G.; Levi, Edi; Majumdar, Adhip P. N.

    2014-01-01

    Accumulating evidence suggests that metformin, a biguanide class of anti-diabetic drugs, possesses anti-cancer properties. However, most of the studies to evaluate therapeutic efficacy of metformin have been on primary cancer. No information is available whether metformin could be effectively used for recurrent cancer, specifically colorectal cancer (CRC) that affects up to 50% of patients treated by conventional chemotherapies. Although the reasons for recurrence are not fully understood, it is thought to be due to re-emergence of chemotherapy-resistant cancer stem/stem-like cells (CSCs/CSLCs). Therefore, development of non-toxic treatment strategies targeting CSCs would be of significant therapeutic benefit. In the current investigation, we have examined the effectiveness of metformin, in combination with 5-fluorouracil and oxaliplatin (FuOx), the mainstay of colon cancer therapeutics, on survival of chemo-resistant colon cancer cells that are highly enriched in CSCs/CSLCs. Our data show that metformin acts synergistically with FuOx to (a) induce cell death in chemo resistant (CR) HT-29 and HCT-116 colon cancer cells, (b) inhibit colonospheres formation and (c) enhance colonospheres disintegration. In vitro cell culture studies have further demonstrated that the combinatorial treatment inhibits migration of CR colon cancer cells. These changes were associated with increased miRNA 145 and reduction in miRNA 21. Wnt/β-catenin signaling pathway was also down-regulated indicating its pivotal role in regulating the growth of CR colon cancer cells. Data from SCID mice xenograft model of CR HCT-116 and CR HT-29 cells show that the combination of metformin and FuOX is highly effective in inhibiting the growth of colon tumors as evidenced by ∼50% inhibition in growth following 5 weeks of combination treatment, when compared with the vehicle treated controls. Our current data suggest that metformin together with conventional chemotherapy could be an effective treatment

  16. Observations of cancer incidence surveillance in Duluth, Minnesota

    SciTech Connect

    Sigurdson, E.E.

    1983-11-01

    Amphibole asbestos fibers were discovered in the municipal water supply for Duluth, Minnesota in 1973. From the late 1950s through 1976 the entire city population of about 100,000 persons was exposed to asbestos at levels of 1-65 million fibers per liter of water. Surveillance of cancer incidence in the area was initiated to determine the health effect from asbestos ingestion. While statistically significant excesses are present is several primary cancer sites in Duluth residents, lung cancer in Duluth females is the only primary site considered also of biological significance. The mesothelioma incidence was no more than expected. Problems of long-term surveillance of exposed populations considered at risk of environmental cancer are defined and the need for improved study methodologies is emphasized. Use of federal records for follow up of exposed individuals is suggested. 19 references, 5 tables.

  17. Surveillance of patients with hereditary gastrointestinal cancer syndromes.

    PubMed

    Moreira, Leticia; Castells, Antoni

    2016-12-01

    Gastrointestinal cancers are among the most frequent tumors. Although most cases are sporadic, up to 5-6% develops in the context of gastrointestinal hereditary syndromes. These entities have specific characteristics and often a germline mutation identified, thus allowing performing genetic counseling. This review summarizes the most common gastrointestinal hereditary syndromes, focusing on the surveillance recommendations.

  18. Hyperglycemia exacerbates colon cancer malignancy through hexosamine biosynthetic pathway.

    PubMed

    Vasconcelos-Dos-Santos, A; Loponte, H F B R; Mantuano, N R; Oliveira, I A; de Paula, I F; Teixeira, L K; de-Freitas-Junior, J C M; Gondim, K C; Heise, N; Mohana-Borges, R; Morgado-Díaz, J A; Dias, W B; Todeschini, A R

    2017-03-20

    Hyperglycemia is a common feature of diabetes mellitus, considered as a risk factor for cancer. However, its direct effects in cancer cell behavior are relatively unexplored. Herein we show that high glucose concentration induces aberrant glycosylation, increased cell proliferation, invasion and tumor progression of colon cancer. By modulating the activity of the rate-limiting enzyme, glutamine-fructose-6-phosphate amidotransferase (GFAT), we demonstrate that hexosamine biosynthetic pathway (HBP) is involved in those processes. Biopsies from patients with colon carcinoma show increased levels of GFAT and consequently aberrant glycans' expression suggesting an increase of HBP flow in human colon cancer. All together, our results open the possibility that HBP links hyperglycemia, aberrant glycosylation and tumor malignancy, and suggest this pathway as a potential therapeutic target for colorectal cancer.

  19. Incidence and Predictors of Bowel Obstruction in Elderly Patients With Stage IV Colon Cancer

    PubMed Central

    Winner, Megan; Mooney, Stephen J.; Hershman, Dawn L.; Feingold, Daniel L.; Allendorf, John D.; Wright, Jason D.; Neugut, Alfred I.

    2015-01-01

    IMPORTANCE Research has been limited on the incidence, mechanisms, etiology, and treatment of symptoms that require palliation in patients with terminal cancer. Bowel obstruction (BO) is a common complication of advanced abdominal cancer, including colon cancer, for which small, single-institution studies have suggested an incidence rate of 15% to 29%. Large population-based studies examining the incidence or risk factors associated with BO in cancer are lacking. OBJECTIVE To investigate the incidence and risk factors associated with BO in patients with stage IV colon cancer. DESIGN AND SETTING Retrospective cohort, population-based study of patients in the Surveillance, Epidemiology, and End Results and Medicare claims linked databases who were diagnosed as having stage IV colon cancer from January 1, 1991, through December 31, 2005. PATIENTS Patients 65 years or older with stage IV colon cancer (n = 12 553). MAIN OUTCOMES AND MEASURES Time to BO, defined by inpatient hospitalization for BO. We used Cox proportional hazards regression models to determine associations between BO and patient, prior treatment, and tumor features. RESULTS We identified 1004 patients with stage IV colon cancer subsequently hospitalized with BO (8.0%). In multivariable analysis, proximal tumor site (hazard ratio, 1.22 [95% CI, 1.07–1.40]), high tumor grade (1.34 [1.16–1.55]), mucinous histological type (1.27 [1.08–1.50]), and nodal stage N2 (1.52 [1.26–1.84]) were associated with increased risk of BO, as was the presence of obstruction at cancer diagnosis (1.75 [1.47–2.04]). A more recent diagnosis was associated with decreased risk of subsequent obstruction (hazard ratio, 0.84 [95% CI, 0.72–0.98]). CONCLUSIONS AND RELEVANCE In this large population of patients with stage IV colon cancer, BO after diagnosis was less common (8.0%) than previously reported. Risk was associated with site and histological type of the primary tumor. Future studies will explore management and

  20. Acidic microenvironment and bone pain in cancer-colonized bone

    PubMed Central

    Yoneda, Toshiyuki; Hiasa, Masahiro; Nagata, Yuki; Okui, Tatsuo; White, Fletcher A

    2015-01-01

    Solid cancers and hematologic cancers frequently colonize bone and induce skeletal-related complications. Bone pain is one of the most common complications associated with cancer colonization in bone and a major cause of increased morbidity and diminished quality of life, leading to poor survival in cancer patients. Although the mechanisms responsible for cancer-associated bone pain (CABP) are poorly understood, it is likely that complex interactions among cancer cells, bone cells and peripheral nerve cells contribute to the pathophysiology of CABP. Clinical observations that specific inhibitors of osteoclasts reduce CABP indicate a critical role of osteoclasts. Osteoclasts are proton-secreting cells and acidify extracellular bone microenvironment. Cancer cell-colonized bone also releases proton/lactate to avoid intracellular acidification resulting from increased aerobic glycolysis known as the Warburg effect. Thus, extracellular microenvironment of cancer-colonized bone is acidic. Acidosis is algogenic for nociceptive sensory neurons. The bone is densely innervated by the sensory neurons that express acid-sensing nociceptors. Collectively, CABP is evoked by the activation of these nociceptors on the sensory neurons innervating bone by the acidic extracellular microenvironment created by bone-resorbing osteoclasts and bone-colonizing cancer cells. As current treatments do not satisfactorily control CABP and can elicit serious side effects, new therapeutic interventions are needed to manage CABP. Understanding of the cellular and molecular mechanism by which the acidic extracellular microenvironment is created in cancer-colonized bone and by which the expression and function of the acid-sensing nociceptors on the sensory neurons are regulated would facilitate to develop novel therapeutic approaches for the management of CABP. PMID:25987988

  1. Occupational Lung Cancer Surveillance in South Korea, 2006-2009

    PubMed Central

    Kim, Hwan-Cheol; Ryu, Jeong-Seon; Won, Jong Uk; Moon, Jai Dong; Kim, Young-Chul; Koh, Sang Baek; Yong, Suk Joong; Kim, Soo Geun; Park, Jae Yong; Kim, Inah; Kim, Jung Il; Kim, Jung Won; Lee, Eui-cheol; Kim, Hyoung-Ryoul; Kim, Dae-Hwan; Kang, Dong Mug; Hong, Yun-Chul

    2010-01-01

    Objectives The lung cancer mortality in Korea has increased remarkably during the last 20 years, and has been the first leading cause of cancer-related deaths since 2000. The aim of the current study was to examine the time trends of occupational lung cancer and carcinogens exposure during the period 2006-2009 in South Korea, by assessing the proportion of occupational burden. Methods We defined occupational lung cancer for surveillance, and developed a reporting protocol and reporting website for the surveillance of occupational lung cancer. The study patients were chosen from 9 participating university hospitals in the following 7 areas: Seoul, Incheon, Wonju, Daejeon, Daegu, Busan, and Gwangju. Results The combined proportion of definite and probable occupational lung cancer among all lung cancers investigated in this study was 10.0%, 8.6%, 10.7%, and 15.8% in the years 2006 to 2009, respectively, with an average of 11.7% over the four-year study period. The main carcinogens were asbestos, crystalline silica, radon, polyaromatic hydrocarbons (PAHs), diesel exhaust particles, chromium, and nickel. Conclusion We estimated that about 11.7% of the incident lung cancer was preventable. This reveals the potential to considerably reduce lung cancer by intervention in occupational fields. PMID:22953173

  2. Sporadic colon cancer murine models demonstrate the value of autoantibody detection for preclinical cancer diagnosis.

    PubMed

    Barderas, Rodrigo; Villar-Vázquez, Roi; Fernández-Aceñero, María Jesús; Babel, Ingrid; Peláez-García, Alberto; Torres, Sofía; Casal, J Ignacio

    2013-10-15

    Although autoantibody detection has been proposed for diagnosis of colorectal cancer, little is known about their initial production and development correlation with cancer progression. Azoxymethane/dextran sodium sulfate (AOM/DSS)-treated mice developed colon adenocarcinoma in the distal colon similar to human sporadic colon cancer. We assessed this model together with AOM and DSS-only models for their applicability to early detection of cancer. All AOM/DSS-treated mice produced autoantibodies to tumor-associated antigens analogous to those observed in human colon cancer patients. Autoantibody response was related to tumor antigen overexpression. Cancer autoantibodies were detected 21 days after starting treatment, when no malignant histopathological features were detectable, and they increased according to tumor progression. When carcinogenesis was induced separately by AOM or DSS, only those mice that developed malignant lesions produced significant levels of autoantibodies. These findings demonstrate that autoantibody development is an early event in tumorigenesis and validates its use for preclinical colon cancer diagnosis.

  3. ERRα metabolic nuclear receptor controls growth of colon cancer cells.

    PubMed

    Bernatchez, Gérald; Giroux, Véronique; Lassalle, Thomas; Carpentier, André C; Rivard, Nathalie; Carrier, Julie C

    2013-10-01

    The estrogen-related receptor alpha (ERRα) is a nuclear receptor that acts primarily as a regulator of metabolic processes, particularly in tissues subjected to high-energy demand. In addition to its control of energy metabolism and mitochondrial biogenesis, ERRα has recently been associated with cancer progression. Notably, increased expression of ERRα has been shown in several cancerous tissues, including breast, ovary and colon. However, additional studies are required to gain insight into the action of ERRα in cancer biology, particularly in non-endocrine-related cancers. Therefore, using a short hairpin RNA-mediated approach, we investigated whether ERRα is required for the rapid growth of colon cancer cells and to maintain their neoplastic metabolic state. Results show that silencing ERRα significantly impaired colon cancer cell proliferation and colony formation in vitro as well as their in vivo tumorigenic capacity. A pronounced delay in G1-to-S cell cycle phase transition was observed in ERRα-depleted cells in association with reduced cyclin-dependent kinase 2 activity and hyperphosphorylated state of the retinoblastoma protein along with disturbed expression of several cell cycle regulators, including p15 and p27. Interestingly, ERRα-depleted HCT116 cells also displayed significant reduction in expression of a large set of key genes to glycolysis, tricarboxylic acid cycle and lipid synthesis. Furthermore, using (14)C isotope tracer analysis, ERRα depletion in colon cancer cells resulted in reduced glucose incorporation and glucose-mediated lipogenesis in these cells. These findings suggest that ERRα coordinates colon cancer cell proliferation and tumorigenic capacity with energy metabolism. Thus, ERRα could represent a promising therapeutic target in colon cancer.

  4. Multimodal nonlinear optical microscopy used to discriminate human colon cancer

    NASA Astrophysics Data System (ADS)

    Adur, Javier; Pelegati, Vitor B.; Bianchi, Mariana; de Thomaz, André A.; Baratti, Mariana O.; Carvalho, Hernandes F.; Casco, Víctor H.; Cesar, Carlos L.

    2013-02-01

    Colon cancer is one of the most diffused cancers in the Western World, ranking third worldwide in frequency of incidence after lung and breast cancers. Even if it is curable when detected and treated early, a more accurate premature diagnosis would be a suitable aim for both cancer prognostic and treatment. Combined multimodal nonlinear optical (NLO) microscopies, such as two-photon excitation fluorescence (TPEF), second-harmonic generation (SHG), third harmonic generation (THG), and fluorescence lifetime imaging microscopy (FLIM) can be used to detect morphological and metabolic changes associated with stroma and epithelial transformation in colon cancer disease. NLO microscopes provide complementary information about tissue microstructure, showing distinctive patterns between normal and malignant human colonic mucosa. Using a set of scoring methods significant differences both in the content, distribution and organization of stroma collagen fibrils, and lifetime components of NADH and FAD cofactors of human colon mucosa biopsies were found. Our results provide a framework for using NLO techniques as a clinical diagnostic tool for human colon cancer, and also suggest that the SHG and FLIM metrics could be applied to other intestinal disorders, which are characterized by abnormal cell proliferation and collagen assembly.

  5. Risk and Surveillance of Cancers in Primary Biliary Tract Disease

    PubMed Central

    Hrad, Valery; Abebe, Yoftahe; Ali, Syed Haris; Velgersdyk, Jared

    2016-01-01

    Primary biliary diseases have been associated in several studies with various malignancies. Understanding the risk and optimizing surveillance strategy of these malignancies in this specific subset of patients are an important facet of clinical care. For instance, primary sclerosing cholangitis is associated with an increased risk for cholangiocarcinoma (which is very challenging to diagnose) and when IBD is present for colorectal cancer. On the other hand, primary biliary cirrhosis patients with cirrhosis or not responding to 12 months of ursodeoxycholic acid therapy are at increased risk of hepatocellular carcinoma. In this review we will discuss in detail the risks and optimal surveillance strategies for patients with primary biliary diseases. PMID:27413366

  6. Shed syndecan-2 enhances tumorigenic activities of colon cancer cells

    PubMed Central

    Choi, Sojoong; Choi, Youngsil; Jun, Eunsung; Kim, In-San; Kim, Seong-Eun; Jung, Sung-Ae; Oh, Eok-Soo

    2015-01-01

    Because earlier studies showed the cell surface heparan sulfate proteoglycan, syndecan-2, sheds from colon cancer cells in culture, the functional roles of shed syndecan-2 were assessed. A non-cleavable mutant of syndecan-2 in which the Asn148-Leu149 residues were replaced with Asn148-Ile149, had decreased shedding, less cancer-associated activities of syndecan-2 in vitro, and less syndecan-2-mediated metastasis of mouse melanoma cells in vivo, suggesting the importance of shedding on syndecan-2-mediated pro-tumorigenic functions. Indeed, shed syndecan-2 from cancer-conditioned media and recombinant shed syndecan-2 enhanced cancer-associated activities, and depletion of shed syndecan-2 abolished these effects. Similarly, shed syndecan-2 was detected from sera of patients from advanced carcinoma (625.9 ng/ml) and promoted cancer-associated activities. Furthermore, a series of syndecan-2 deletion mutants showed that the tumorigenic activity of shed syndecan-2 resided in the C-terminus of the extracellular domain and a shed syndecan-2 synthetic peptide (16 residues) was sufficient to establish subcutaneous primary growth of HT29 colon cancer cells, pulmonary metastases (B16F10 cells), and primary intrasplenic tumor growth and liver metastases (4T1 cells). Taken together, these results demonstrate that shed syndecan-2 directly enhances colon cancer progression and may be a promising therapeutic target for controlling colon cancer development. PMID:25686828

  7. Screening and surveillance approaches in familial pancreatic cancer.

    PubMed

    Canto, Marcia Irene

    2008-07-01

    Screening and surveillance for pancreatic cancer and its precursors is a relatively new indication for endoscopic ultrasound. It provides an alternative approach to the ineffective treatment of mostly incurable symptomatic pancreatic cancer. It is currently reserved for individuals with an increased risk for pancreatic ductal adenocarcinoma, such as those who have inherited genetic syndromes (eg, patients who have Peutz-Jeghers syndrome or hereditary pancreatitis, germline mutation carriers of p16 and BRCA2) and at-risk relatives of patients who have familial pancreatic cancer. This article discusses the rationale for performing screening and surveillance, the types of patients who are eligible for screening, the diagnostic modalities and technique for screening, the diagnostic yield of screening, and the ongoing research.

  8. Clostridium difficile colonization in preoperative colorectal cancer patients.

    PubMed

    Zheng, Yi; Luo, Yun; Lv, Yinxiang; Huang, Chen; Sheng, Qinsong; Zhao, Peng; Ye, Julian; Jiang, Weiqin; Liu, Lulu; Song, Xiaojun; Tong, Zhou; Chen, Wenbin; Lin, Jianjiang; Tang, Yi-Wei; Jin, Dazhi; Fang, Weijia

    2017-01-02

    The entire process of Clostridium difficile colonization to infection develops in large intestine. However, the real colonization pattern of C. difficile in preoperative colorectal cancer patients has not been studied. In this study, 33 C. difficile strains (16.1%) were isolated from stool samples of 205 preoperative colorectal cancer patients. C. difficile colonization rates in lymph node metastasis patients (22.3%) were significantly higher than lymph node negative patients (10.8%) (OR=2.314, 95%CI=1.023-5.235, P =0.025). Meanwhile, patients positive for stool occult blood had lower C. difficile colonization rates than negative patients (11.5% vs. 24.0%, OR=0.300, 95%CI=0.131-0.685, P =0.019). A total of 16 sequence types were revealed by multilocus sequence typing. Minimum spanning tree and time-space cluster analysis indicated that all C. difficile isolates were epidemiologically unrelated. Antibiotic susceptibility testing showed all isolates were susceptible to vancomycin and metronidazole. The results suggested that the prevalence of C. difficile colonization is high in preoperative colorectal cancer patients, and the colonization is not acquired in the hospital. Since lymph node metastasis colorectal cancer patients inevitably require adjuvant chemotherapy and C. difficile infection may halt the ongoing treatment, the call for sustained monitoring of C. difficile in those patients is apparently urgent.

  9. Adjuvant therapy for colon cancer in the new millenium.

    PubMed

    Rao, S; Cunningham, D

    2003-01-01

    A significant proportion of patients with colon cancer who undergo curative surgical resection develop metastatic disease. Over the last 20 years large prospective randomised studies have demonstrated a clear survival benefit for patients with stage III colon cancer who are treated with adjuvant 5FU based chemotherapy. At the present time 6 months of 5FU and leucovorin is generally considered the standard adjuvant therapy. For stage II disease the routine use of adjuvant treatment remains controversial. Newer drugs such as oxaliplatin, irinotecan, and the oral fluoropyrimidines have proven active in advanced colorectal cancer and are currently being evaluated in the adjuvant setting. Molecular markers for this disease are being identified and may help define those patients who would benefit from therapy. The integration of adjuvant immunotherapy with conventional chemotherapy offers the potential to improve the long-term outcome for surgically resected colon cancer.

  10. Products of the colonic microbiota mediate the effects of diet on colon cancer risk.

    PubMed

    O'Keefe, Stephen J D; Ou, Junhai; Aufreiter, Susanne; O'Connor, Deborah; Sharma, Sumit; Sepulveda, Jorge; Fukuwatari, Tsutomu; Shibata, Katsumi; Mawhinney, Thomas

    2009-11-01

    It is estimated that most colon cancers can be attributed to dietary causes. We have hypothesized that diet influences the health of the colonic mucosa through interaction with the microbiota and that it is the milieu interior that regulates mucosal proliferation and therefore cancer risk. To validate this further, we compared colonic contents from healthy 50- to 65-y-old people from populations with high and low risk, specifically low risk Native Africans (cancer incidence <1:100,000; n = 17), high risk African Americans (risk 65:100,000; n = 17), and Caucasian Americans (risk 50:100,000; n = 18). Americans typically consume a high-animal protein and -fat diet, whereas Africans consume a staple diet of maize meal, rich in resistant starch and low in animal products. Following overnight fasting, rapid colonic evacuation was performed with 2 L polyethylene glycol. Total colonic evacuants were analyzed for SCFA, vitamins, nitrogen, and minerals. Total SCFA and butyrate were significantly higher in Native Africans than in both American groups. Colonic folate and biotin content, measured by Lactobacillus rhamnoses and Lactobacillus plantarum ATCC 8014 bioassay, respectively, exceeded normal daily dietary intakes. Compared with Africans, calcium and iron contents were significantly higher in Caucasian Americans and zinc content was significantly higher in African Americans, but nitrogen content did not differ among the 3 groups. In conclusion, the results support our hypothesis that the microbiota mediates the effect diet has on colon cancer risk by their generation of butyrate, folate, and biotin, molecules known to play a key role in the regulation of epithelial proliferation.

  11. Aberrant DNA methylation occurs in colon neoplasms arising in the azoxymethane colon cancer model

    PubMed Central

    Borinstein, Scott C.; Conerly, Melissa; Dzieciatkowski, Slavomir; Biswas, Swati; Washington, M. Kay; Trobridge, Patty; Henikoff, Steve; Grady, William M.

    2010-01-01

    Mouse models of intestinal tumors have advanced our understanding of the role of gene mutations in colorectal malignancy. However, the utility of these systems for studying the role of epigenetic alterations in intestinal neoplasms remains to be defined. Consequently, we assessed the role of aberrant DNA methylation in the azoxymethane (AOM) rodent model of colon cancer. AOM induced tumors display global DNA hypomethylation, which is similar to human colorectal cancer. We next assessed the methylation status of a panel of candidate genes previously shown to be aberrantly methylated in human cancer or in mouse models of malignant neoplasms. This analysis revealed different patterns of DNA methylation that were gene specific. Zik1 and Gja9 demonstrated cancer-specific aberrant DNA methylation, whereas, Cdkn2a/p16, Igfbp3, Mgmt, Id4, and Cxcr4 were methylated in both the AOM tumors and normal colon mucosa. No aberrant methylation of Dapk1 or Mlt1 was detected in the neoplasms, but normal colon mucosa samples displayed methylation of these genes. Finally, p19Arf, Tslc1, Hltf, and Mlh1 were unmethylated in both the AOM tumors and normal colon mucosa. Thus, aberrant DNA methylation does occur in AOM tumors, although the frequency of aberrantly methylated genes appears to be less common than in human colorectal cancer. Additional studies are necessary to further characterize the patterns of aberrantly methylated genes in AOM tumors. PMID:19777566

  12. SRPK2 promotes the growth and migration of the colon cancer cells.

    PubMed

    Wang, Jian; Wu, Hai-Feng; Shen, Wei; Xu, Dong-Yan; Ruan, Ting-Yan; Tao, Guo-Qing; Lu, Pei-Hua

    2016-07-15

    Colon cancer is one of the major causes of cancer-related death in the world. Understanding the molecular mechanism underlying this malignancy will facilitate the diagnosis and treatment. Serine-arginine protein kinase 2 (SRPK2) has been reported to be upregulated in several cancer types. However, its expression and functions in colon cancer remains unknown. In this study, it was found that the expression of SRPK2 was up-regulated in the clinical colon cancer samples. Overexpression of SRPK2 promoted the growth and migration of colon cancer cells, while knocking down the expression of SRPK2 inhibited the growth, migration and tumorigenecity of colon cancer cells. Molecular mechanism studies revealed that SRPK2 activated ERK signaling in colon cancer cells. Taken together, our study demonstrated the tumor promoting roles of SRPK2 in colon cancer cells and SRPK2 might be a promising therapeutic target for colon cancer.

  13. Near-infrared Mueller matrix imaging for colonic cancer detection

    NASA Astrophysics Data System (ADS)

    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 (<5s) Muller matrix imaging system with dual-rotating waveplates was developed. 16 (4 by 4) full Mueller matrices of the 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.

  14. Adjuvant Chemotherapy for Stage II Right- and Left-Sided Colon Cancer: Analysis of SEER-Medicare Data

    PubMed Central

    Weiss, Jennifer M.; Schumacher, Jessica; Allen, Glenn O.; Neuman, Heather; Lange, Erin O’Connor; LoConte, Noelle K.; Greenberg, Caprice C.; Smith, Maureen A.

    2014-01-01

    Purpose Survival benefit from adjuvant chemotherapy is established for stage III colon cancer; however, uncertainty exists for stage II patients. Tumor heterogeneity, specifically microsatellite instability (MSI) which is more common in right-sided cancers, may be the reason for this observation. We examined the relationship between adjuvant chemotherapy and overall 5-year mortality for stage II colon cancer by location (right- versus left-side) as a surrogate for MSI. Methods Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified Medicare beneficiaries from 1992 to 2005 with AJCC stage II (n=23,578) and III (n=17,148) primary adenocarcinoma of the colon who underwent surgery for curative intent. Overall 5-year mortality was examined with Kaplan-Meier survival analysis and Cox proportional hazards regression with propensity score weighting. Results Eighteen percent (n=2,941) of stage II patients with right-sided cancer and 22% (n=1,693) with left-sided cancer received adjuvant chemotherapy. After adjustment, overall 5-year survival benefit from chemotherapy was observed only for stage III patients (right-sided: HR 0.64; 95% CI, 0.59–0.68, p<0.001 and left-sided: HR 0.61; 95% CI, 0.56–0.68, p<0.001). No survival benefit was observed for stage II patients with either right-sided (HR 0.97; 95% CI, 0.87–1.09, p=0.64) or left-sided cancer (HR 0.97; 95% CI, 0.84–1.12, p=0.68). Conclusions Among Medicare patients with stage II colon cancer, a substantial number receive adjuvant chemotherapy. Adjuvant chemotherapy did not improve overall 5-year survival for either right- or left-sided colon cancers. Our results reinforce existing guidelines and should be considered in treatment algorithms for older adults with stage II colon cancer. PMID:24643898

  15. Cancer Intervention and Surveillance Modeling Network (CISNET)

    Cancer.gov

    CISNET is a consortium of NCI-sponsored investigators that use statistical modeling to improve our understanding of cancer control interventions in prevention, screening, and treatment and their effects on population trends in incidence and mortality.

  16. Rural-Urban Differences in Colon Cancer Risk in Blacks and Whites: The North Carolina Colon Cancer Study

    ERIC Educational Resources Information Center

    Yeomans Kinney, Anita; Harrell, Janna; Slattery, Marty; Martin, Christopher; Sandler, Robert S.

    2006-01-01

    Context: Geographic and racial variations in cancer incidence have been observed. Studies of colorectal carcinoma indicate a higher incidence and mortality rate for blacks than for whites in the United States. Purpose: We evaluated the effect of rural versus urban residence on colon cancer risk and stage of disease at diagnosis in blacks and…

  17. Whether regional lymph nodes evaluation should be equally required for both right and left colon cancer

    PubMed Central

    Jiang, Zheng; Hu, Hanqing; Zhao, Zhixun; Wang, Song; Chen, Yinggang; Wang, Guiyu; Wang, Xishan

    2016-01-01

    Despite the adequacy of nodal evaluation was gradually improved for colon cancer, the disparity in nodal examination for right colon cancer (RCC) and left colon cancer (LCC) still begs the question of whether 12 nodes is an appropriate threshold for both RCC and LCC. From Surveillance, Epidemiology, and End-Results (SEER) database, we identified 53897 RCC patients and 11822 LCC patients. Compared with LCC patients, RCC patients examined more lymph nodes (18.7 vs 16.3), and more likely to examine ≥12 nodes (P<0.001), whereas RCC patients showed lower rates of node positivity (P<0.001). To balance the nodal disparity between RCC and LCC, we revised the 12-node measure based on different tumor locations. With the X-tile, we determined 15 as the optimal node number for RCC and 11 for LCC. To validate the availability of this revised nodal evaluation, the 5-year cancer specific survival (CSS) was calculated according to the optimal node number in RCC and LCC patients, Cox's regression model were used to further assess the prognostic value of this revised nodal evaluation. The results showed that 5-year CSSs were significantly improved for RCC patients with ≥15 lymph nodes, and also for LCC patients with ≥11 lymph nodes (P<0.001). This revised nodal evaluation could also improve the rate of nodal positivity and long-term survival in both RCC and LCC patients compared with 12-node measure. Therefore, the lymph node examination should be discriminately evaluated for RCC and LCC, instead of using 12-node measure to colon cancer as a whole. PMID:27494866

  18. Oncostatic effects of fluoxetine in experimental colon cancer models.

    PubMed

    Kannen, Vinicius; Garcia, Sergio Britto; Silva, Wilson A; Gasser, Martin; Mönch, Romana; Alho, Eduardo Joaquim Lopes; Heinsen, Helmut; Scholz, Claus-Jürgen; Friedrich, Mike; Heinze, Katrin Gertrud; Waaga-Gasser, Ana Maria; Stopper, Helga

    2015-09-01

    Colon cancer is one of the most common tumors in the human population. Recent studies have shown a reduced risk for colon cancer in patients given the antidepressant fluoxetine (FLX). The exact mechanism by which FLX might protect from colon cancer remains however controversial. Here, FLX reduced the development of different colon tumor xenografts, as well as proliferation in hypoxic tumor areas within them. FLX treatment also decreased microvessel numbers in tumors. Although FLX did not increase serum and tumor glucose levels as much as the colon chemotherapy gold standard Fluorouracil did, lactate levels were significantly augmented within tumors by FLX treatment. The gene expression of the MCT4 lactate transporter was significantly downregulated. Total protein amounts from the third and fifth mitochondrial complexes were significantly decreased by FLX in tumors. Cell culture experiments revealed that FLX reduced the mitochondrial membrane potential significantly and disabled the reactive oxygen species production of the third mitochondrial complex. Furthermore, FLX arrested hypoxic colon tumor cells in the G0/G1 phase of the cell-cycle. The expression of key cell-cycle-related checkpoint proteins was enhanced in cell culture and in vivo experiments. Therefore, we suggest FLX impairs energy generation, cell cycle progression and proliferation in tumor cells, especially under condition of hypoxia. This then leads to reduced microvessel formation and tumor shrinkage in xenograft models.

  19. The Effect of Care Setting in the Delivery of High-Value Colon Cancer Care

    PubMed Central

    Veenstra, Christine M.; Epstein, Andrew J.; Liao, Kaijun; Morris, Arden M.; Pollack, Craig E.; Armstrong, Katrina A.

    2015-01-01

    BACKGROUND The effect of care setting on value of colon cancer care is unknown. METHODS A Surveillance, Epidemiology, and End Results (SEER)-Medicare cohort study of 6544 patients aged ≥66 years with stage IV colon cancer (based on the American Joint Committee on Cancer staging system) who were diagnosed between 1996 and 2005 was performed. All patients were followed through December 31, 2007. Using outpatient and carrier claims, patients were assigned to a treating hospital based on the hospital affiliation of the primary oncologist. Hospitals were classified academic or nonacademic using the SEER-Medicare National Cancer Institute Hospital File. RESULTS Of the 6544 patients, 1605 (25%) received care from providers affiliated with academic medical centers. The unadjusted median cancer-specific survival was 16.0 months at academic medical centers versus 13.9 months at nonacademic medical centers (P<.001). After adjustment, treatment at academic hospitals remained significantly associated with a reduced risk of death from cancer (hazard ratio, 0.87; 95% confidence interval [95% CI], 0.82–0.93 [P<.001]). Adjusted mean 12-month Medicare spending was $8571 higher at academic medical centers (95% CI, $2340–$14,802; P =.007). The adjusted median cost was $1559 higher at academic medical centers; this difference was not found to be statistically significant (95% CI, −$5239 to $2122; P =.41). A small percentage of patients who received very expensive care skewed the difference in mean cost; the only statistically significant difference in adjusted costs in quantile regressions was at the 99.9th percentile of costs (P<.001). CONCLUSIONS Among Medicare beneficiaries with stage IV colon cancer, treatment by a provider affiliated with an academic medical center was associated with a 2 month improvement in overall survival. Except for patients in the 99.9th percentile of the cost distribution, costs at academic medical centers were not found to be significantly

  20. [Surveillance of patients after colonoscopic polypectomy and curative resection of colorectal cancer].

    PubMed

    Niv, Yaron; Half, Betsi; Moshkowitz, Menachem; Kariv, Revital; Vilkin, Alex; Levi, Zohar

    2010-10-01

    The position paper of the GastrointestinaL Oncology Section of the Israeli Gastroenterological Association recommends specific guidelines for surveillance after polypectomy and curative resection of colorectal cancer. Periodic colonoscopy is necessary for early detection of metachronous lesions or cancer recurrence. After polypectomy of a simple hyperplasic polyp, colonoscopy is repeated in 10 years. Small adenoma dictates colonoscopy after 5-10 years. In the case of advanced adenoma, repeat coLonoscopy is to be conducted after 3 years. The personal impression of the colonoscopists may advance procedures to an earlier colonoscopy, especially after piecemeal polypectomy of a large sessile polyp. Fecal occult blood test or any other screening procedures are not needed after polypectomy. Colonoscopy, carcinoembrionic antigen examination (CEA) and liver imaging are necessary for surveillance after curative resection of colorectal cancer, and improve survival. Total colonoscopy should be performed before the operation or in cases with obstructive carcinoma, colonic imaging should be completed with virtual colonoscopy. Total colonoscopy should be performed 3-6 months after surgery if not conducted previously. The next follow-up is needed 3 and 5 years after the operation. After low anterior resection, the recurrence rate may be high and patients who have not undergone radiation therapy nor mesorectal resection should undergo sigmoidoscopy every 3-6 months for 2-3 years after surgery.

  1. Crizotinib induces PUMA-dependent apoptosis in colon cancer cells.

    PubMed

    Zheng, Xingnan; He, Kan; Zhang, Lin; Yu, Jian

    2013-05-01

    Oncogenic alterations in MET or anaplastic lymphoma kinase (ALK) have been identified in a variety of human cancers. Crizotinib (PF02341066) is a dual MET and ALK inhibitor and approved for the treatment of a subset of non-small cell lung carcinoma and in clinical development for other malignancies. Crizotinib can induce apoptosis in cancer cells, whereas the underlying mechanisms are not well understood. In this study, we found that crizotinib induces apoptosis in colon cancer cells through the BH3-only protein PUMA. In cells with wild-type p53, crizotinib induces rapid induction of PUMA and Bim accompanied by p53 stabilization and DNA damage response. The induction of PUMA and Bim is mediated largely by p53, and deficiency in PUMA or p53, but not Bim, blocks crizotinib-induced apoptosis. Interestingly, MET knockdown led to selective induction of PUMA, but not Bim or p53. Crizotinib also induced PUMA-dependent apoptosis in p53-deficient colon cancer cells and synergized with gefitinib or sorafenib to induce marked apoptosis via PUMA in colon cancer cells. Furthermore, PUMA deficiency suppressed apoptosis and therapeutic responses to crizotinib in xenograft models. These results establish a critical role of PUMA in mediating apoptotic responses of colon cancer cells to crizotinib and suggest that mechanisms of oncogenic addiction to MET/ALK-mediated survival may be cell type-specific. These findings have important implications for future clinical development of crizotinib.

  2. The integrated proactive surveillance system for prostate cancer.

    PubMed

    Wang, Haibin; Yatawara, Mahendra; Huang, Shao-Chi; Dudley, Kevin; Szekely, Christine; Holden, Stuart; Piantadosi, Steven

    2012-01-01

    In this paper, we present the design and implementation of the integrated proactive surveillance system for prostate cancer (PASS-PC). The integrated PASS-PC is a multi-institutional web-based system aimed at collecting a variety of data on prostate cancer patients in a standardized and efficient way. The integrated PASS-PC was commissioned by the Prostate Cancer Foundation (PCF) and built through the joint of efforts by a group of experts in medical oncology, genetics, pathology, nutrition, and cancer research informatics. Their main goal is facilitating the efficient and uniform collection of critical demographic, lifestyle, nutritional, dietary and clinical information to be used in developing new strategies in diagnosing, preventing and treating prostate cancer.The integrated PASS-PC is designed based on common industry standards - a three tiered architecture and a Service- Oriented Architecture (SOA). It utilizes open source software and programming languages such as HTML, PHP, CSS, JQuery, Drupal and MySQL. We also use a commercial database management system - Oracle 11g. The integrated PASS-PC project uses a "confederation model" that encourages participation of any interested center, irrespective of its size or location. The integrated PASS-PC utilizes a standardized approach to data collection and reporting, and uses extensive validation procedures to prevent entering erroneous data. The integrated PASS-PC controlled vocabulary is harmonized with the National Cancer Institute (NCI) Thesaurus. Currently, two cancer centers in the USA are participating in the integrated PASS-PC project.THE FINAL SYSTEM HAS THREE MAIN COMPONENTS: 1. National Prostate Surveillance Network (NPSN) website; 2. NPSN myConnect portal; 3. Proactive Surveillance System for Prostate Cancer (PASS-PC). PASS-PC is a cancer Biomedical Informatics Grid (caBIG) compatible product. The integrated PASS-PC provides a foundation for collaborative prostate cancer research. It has been built to

  3. Carbohydrate-containing molecules as potential biomarkers in colon cancer.

    PubMed

    Joo, Eun Ji; Weyers, Amanda; Li, Guoyun; Gasimli, Leyla; Li, Lingyun; Choi, Won Jun; Lee, Kyung Bok; Linhardt, Robert J

    2014-04-01

    Glycans play a critical role in physiological and pathological processes through interaction with a variety of ligands. Altered expression and dysregulation of these molecules can cause aberrant cellular function such as malignancy. Glycomics provide information of the structure and function of glycans, glycolipids, and glycoproteins such as proteoglycans, and may help to predict cancer development and progression as biomarkers. In this report, we compared the expression of proteoglycans, the content and structure of glycosaminoglycans and glycolipids between patient-matched normal and cancer tissues obtained from colon cancer patients. Tumor-related proteoglycans, glypican-3, and syndecan-1 showed downregulation in cancer tissues compared to normal tissues. In cancer tissue, the total amount of chondroitin sulfate (CS)/dermatan sulfate and heparan sulfate were lower and, interestingly, the level of disaccharide units of both 4S6S (CS-E) and 6S (CS-C) were higher compared to normal tissue. Also, overall lipids including glycolipids, a major glycomics target, were analyzed by hydrophilic interaction liquid chromatography mass spectrometry. Increase of lyso-phosphatidylcholine (phospholipid), sphingomyelin (sphigolipid), and four types of glycolipids (glucosylceramide, lactosylceramide, monosialic acid ganglioside, and globoside 4) in cancer tissue showed the possibility as potential biomarkers in colon cancer. While requiring the need for careful interpretation, this type of broad investigation gives us a better understanding of pathophysiological roles on glycosaminoglycans and glycolipids and might be a powerful tool for colon cancer diagnosis.

  4. Carbohydrate-Containing Molecules as Potential Biomarkers in Colon Cancer

    PubMed Central

    Joo, Eun Ji; Weyers, Amanda; Li, Guoyun; Gasimli, Leyla; Li, Lingyun; Choi, Won Jun

    2014-01-01

    Abstract Glycans play a critical role in physiological and pathological processes through interaction with a variety of ligands. Altered expression and dysregulation of these molecules can cause aberrant cellular function such as malignancy. Glycomics provide information of the structure and function of glycans, glycolipids, and glycoproteins such as proteoglycans, and may help to predict cancer development and progression as biomarkers. In this report, we compared the expression of proteoglycans, the content and structure of glycosaminoglycans and glycolipids between patient-matched normal and cancer tissues obtained from colon cancer patients. Tumor-related proteoglycans, glypican-3, and syndecan-1 showed downregulation in cancer tissues compared to normal tissues. In cancer tissue, the total amount of chondroitin sulfate (CS)/dermatan sulfate and heparan sulfate were lower and, interestingly, the level of disaccharide units of both 4S6S (CS-E) and 6S (CS-C) were higher compared to normal tissue. Also, overall lipids including glycolipids, a major glycomics target, were analyzed by hydrophilic interaction liquid chromatography mass spectrometry. Increase of lyso-phosphatidylcholine (phospholipid), sphingomyelin (sphigolipid), and four types of glycolipids (glucosylceramide, lactosylceramide, monosialic acid ganglioside, and globoside 4) in cancer tissue showed the possibility as potential biomarkers in colon cancer. While requiring the need for careful interpretation, this type of broad investigation gives us a better understanding of pathophysiological roles on glycosaminoglycans and glycolipids and might be a powerful tool for colon cancer diagnosis. PMID:24502776

  5. Early detection of COPD is important for lung cancer surveillance.

    PubMed

    Sekine, Yasuo; Katsura, Hideki; Koh, Eitetsu; Hiroshima, Kenzo; Fujisawa, Takehiko

    2012-05-01

    It is well known that chronic obstructive pulmonary disease (COPD) is a significant risk factor for lung cancer. Approximately 1% of COPD patients develop lung cancer every year, which may be associated with genetic susceptibility to cigarette smoke. Chronic inflammation caused by toxic gases can induce COPD and lung cancer. Inflammatory mediators may promote the growth of bronchioalveolar stem cells, and activation of nuclear factor-κB and signal transducer and activator of transcription 3 play crucial roles in the development of lung cancer from COPD. Low-dose computed tomography (LDCT) is an effective procedure for the early detection of lung cancer in high-risk patients. However, determining which patients should be screened for lung cancer in a primary care setting is difficult. In this article, we review the epidemiology and aetiology of lung cancer associated with COPD, verify the efficacy of lung cancer screening by LDCT, and discuss the importance of early detection of COPD for lung cancer surveillance. We propose that, for the prevention of both diseases, COPD screening in smokers should be initiated as early as possible, so they can stop smoking and so that candidates for an efficient lung cancer screening programme can be identified.

  6. Management of familial cancer: sequencing, surveillance and society.

    PubMed

    Samuel, Nardin; Villani, Anita; Fernandez, Conrad V; Malkin, David

    2014-12-01

    The clinical management of familial cancer begins with recognition of patterns of cancer occurrence suggestive of genetic susceptibility in a proband or pedigree, to enable subsequent investigation of the underlying DNA mutations. In this regard, next-generation sequencing of DNA continues to transform cancer diagnostics, by enabling screening for cancer-susceptibility genes in the context of known and emerging familial cancer syndromes. Increasingly, not only are candidate cancer genes sequenced, but also entire 'healthy' genomes are mapped in children with cancer and their family members. Although large-scale genomic analysis is considered intrinsic to the success of cancer research and discovery, a number of accompanying ethical and technical issues must be addressed before this approach can be adopted widely in personalized therapy. In this Perspectives article, we describe our views on how the emergence of new sequencing technologies and cancer surveillance strategies is altering the framework for the clinical management of hereditary cancer. Genetic counselling and disclosure issues are discussed, and strategies for approaching ethical dilemmas are proposed.

  7. Surveillance, Diagnosis, Treatment, and Outcome of Liver Cancer in Japan

    PubMed Central

    Kudo, Masatoshi

    2015-01-01

    Background Hepatocellular carcinoma (HCC) is the fifth most common type of cancer and the third leading cause of cancer-related death worldwide. HCC is most common in Asia, but its prevalence is rapidly increasing in Western countries; consequently, HCC is a global medical issue that urgently needs to be addressed. Japan is the only developed country that has experienced both hepatitis B-related and hepatitis C-related HCC and has a long history of innovation when it comes to new diagnostic and therapeutic modalities, such as computed tomography angiography, anatomical resection, ablation, and transarterial chemoembolization. Among these innovations, a nationwide surveillance program was well established by the 1980s, and such a long-term national program does not exist anywhere else in the world. Summary More than 60% of the initially detected HCCs in Japan are Barcelona Clinic Liver Cancer stage 0 or A, which can undergo curative therapies such as resection, ablation, or transplantation. The recent 5-year survival rate of HCC patients in Japan was 43% and the median survival time was 50 months. In addition, both incidence and mortality rates are drastically declining as a result of the successful surveillance program, careful diagnostic flow, and extensive repeated treatments. Key Message Japan's successful model in the surveillance, diagnosis, and treatment of HCC should be adopted as widely as possible to improve the survival of HCC patients worldwide. PMID:26020028

  8. Procaine Induces Epigenetic Changes in HCT116 Colon Cancer Cells

    PubMed Central

    Samy, Mariam B.; Said, Osama A. M.; El-Zawahri, Mokhtar M.

    2016-01-01

    Colon cancer is the third most commonly diagnosed cancer in the world, and it is the major cause of morbidity and mortality throughout the world. The present study aimed at treating colon cancer cell line (HCT116) with different chemotherapeutic drug/drug combinations (procaine, vorinostat “SAHA,” sodium phenylbutyrate, erlotinib, and carboplatin). Two different final concentrations were applied: 3 μM and 5 μM. Trypan blue test was performed to assess the viability of the cell before and after being treated with the drugs. The data obtained showed that there was a significant decrease in the viability of cells after applying the chemotherapeutic drugs/drug combinations. Also, DNA fragmentation assay was carried out to study the effect of these drugs on the activation of apoptosis-mediated DNA degradation process. The results indicated that all the drugs/drug combinations had a severe effect on inducing DNA fragmentation. Global DNA methylation quantification was performed to identify the role of these drugs individually or in combination in hypo- or hypermethylating the CpG dinucleotide all over the genome of the HCT116 colon cancer cell line. Data obtained indicated that different combinations had different effects in reducing or increasing the level of methylation, which might indicate the effectiveness of combining drugs in treating colon cancer cells. PMID:27843649

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

    PubMed

    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.

  10. Observations of cancer incidence surveillance in Duluth, Minnesota.

    PubMed Central

    Sigurdson, E E

    1983-01-01

    In 1973, amphibole asbestos fibers were discovered in the municipal water supply of Duluth, Minnesota. The entire city population of approximately 100,000 was exposed from the late 1950s through 1976 at levels of 1-65 million fibers per liter of water. Because of previous epidemiologic studies that linked mesothelioma, lung and gastrointestinal cancers to occupational exposure to asbestos, surveillance of cancer incidence in residents of Duluth was initiated to determine the health effect from ingestion of asbestos. The methodology of the Third National Cancer Survey (TNCS) and SEER Program was used. Duluth 1969-1971 rates were compared with TNCS rates for the cities of Minneapolis and St. Paul during 1969-1971; Duluth rates during 1974-1976 are compared with Duluth 1969-1971; Duluth rates during 1979-1980 are compared with Duluth 1969-1971 and with Iowa SEER; and a table of the occurrence of malignant mesothelioma is presented. Statistically significant excesses are observed in several primary sites in Duluth residents. However, lung cancer in Duluth females is the only primary site considered also of biological significance. The mesothelioma incidence rate is no more than expected. This paper also describes the problems of long-term surveillance of exposed populations considered at risk of environment cancer, the need for improved study methodologies and the use of federal records for follow up of exposed individuals. PMID:6662096

  11. Management and Outcomes of Bowel Obstruction in Patients with Stage IV Colon Cancer: A Population-Based Cohort Study

    PubMed Central

    Winner, Megan; Mooney, Stephen J.; Hershman, Dawn L.; Feingold, Daniel L.; Allendorf, John D.; Wright, Jason D.; Neugut, Alfred I.

    2015-01-01

    BACKGROUND Bowel obstruction is a common complication of late-stage abdominal cancer, especially colon cancer, which has been investigated predominantly in small, single-institution studies. OBJECTIVE We used a large, population-based data set to explore the surgical treatment of bowel obstruction and its outcomes after hospitalization for obstruction among patients with stage IV colon cancer. DESIGN This was a retrospective cohort study. SETTING AND PATIENTS We identified 1004 patients aged 65 years or older in the Surveillance, Epidemiology and End Results-Medicare database diagnosed with stage IV colon cancer January 1, 1991 to December 31, 2005, who were later hospitalized for bowel obstruction. MAIN OUTCOME MEASURES We describe outcomes after hospitalization and analyzed the associations between surgical treatment of obstruction and outcomes. RESULTS Hospitalization for bowel obstruction occurred a median of 7.4 months after colon cancer diagnosis, and median survival after obstruction was approximately 2.5 months. Median hospitalization for obstruction was about 1 week and in-hospital mortality was 12.7%. Between discharge and death, 25% of patients were readmitted to the hospital at least once for obstruction, and, on average, patients lived 5 days out of the hospital for every day in the hospital between obstruction diagnosis and death. Survival was 3 times longer in those whose obstruction claims suggested an adhesive obstruction origin. In multivariable models, surgical compared with nonsurgical management was not associated with prolonged survival (p = 0.134). LIMITATIONS Use of an administrative database did not allow determination of quality of life or relief of obstruction as an outcome, nor could nonsurgical interventions, eg, endoscopic stenting or octreotide, be assessed. CONCLUSIONS In this population-based study of patients with stage IV colon cancer who had bowel obstruction, overall survival following obstruction was poor irrespective of

  12. LIGHT elevation enhances immune eradication of colon cancer metastases.

    PubMed

    Qiao, Guilin; Qin, Jianzhong; Kunda, Nicholas; Calata, Jed; Mahmud, Dolores; Gann, Peter H; Fu, Yang-Xin; Rosenberg, Steven A; Prabhakar, Bellur S; Maker, Ajay V

    2017-03-01

    The majority of colon cancer patients will develop advanced disease with the liver being the most common site of metastatic disease. Patients with increased numbers of tumor-infiltrating lymphocytes in primary colon tumors and liver metastases have improved outcomes. However, the molecular factors which could empower anti-tumor immune responses in this setting remained to be elucidated. We reported that the immunostimulatory cytokine LIGHT (TNFSF14) in the microenvironment of colon cancer metastases associates with improved patient survival, and here we demonstrate in an immunocompetent murine model that colon tumors expressing LIGHT stimulate lymphocyte proliferation and tumor-cell specific anti-tumor immune responses. In this model, increasing LIGHT expression in the microenvironment of either primary tumors or liver metastases triggered regression of established tumors and slowed the growth of liver metastases, driven by cytotoxic T-lymphocyte mediated anti-tumor immunity. These responses corresponded with significant increases in tumor-infiltrating lymphocytes and increased expression of lymphocyte-homing signals in the metastatic tumors. Further, we demonstrated evidence of durable tumor-specific anti-tumor immunity. In conclusion, increasing LIGHT expression increased T-cell proliferation, activation, and infiltration, resulting in enhanced tumor-specific immune-mediated tumor regressions in primary tumors and colorectal liver metastases. Mechanisms to increase LIGHT in the colon cancer microenvironment warrant further investigation and hold promise as an immunotherapeutic strategy.

  13. Therapeutic opportunities from tumour biology in metastatic colon cancer.

    PubMed

    McLeod, H L; McKay, J A; Collie-Duguid, E S; Cassidy, J

    2000-08-01

    Tumour metastasis is the major cause of morbidity and mortality from colorectal cancer. While improvements in quality of life and patient survival have been made over the past 10 years, the majority of patients with metastatic colorectal cancer will die from their disease. As knowledge of the biology of colon cancer and its invasion/metastasis programme evolve, this presents new therapeutic opportunities for pharmacological and genetic intervention. This review discusses the current approaches to metastatic colorectal cancer therapy, details genomic and biological variance between primary and metastatic tumours, and highlights approaches for harnessing these differences to improve therapy.

  14. Late metastatic colon cancer masquerading as primary jejunal carcinoma

    PubMed Central

    Meshikhes, A-WN; Joudeh, AA

    2016-01-01

    Metastasis to the small bowel from a previously resected colorectal cancer is rare and may erroneously be diagnosed as a primary small bowel carcinoma. It usually occurs several years after the primary resection. We present the case of a 67-year-old man who had undergone left hemicolectomy for colon cancer 3 years earlier and returned with subacute small bowel obstruction. This was initially thought, based on preoperative radiological findings and normal colonoscopic examination, to be due a primary jejunal cancer. Even at surgery, the lesion convincingly appeared as an obstructing primary small bowel carcinoma. However, the histology of the resected small bowel revealed metastatic colon cancer. This rare and an unusual metastatic occurrence some years after the primary resection is described and reviewed. PMID:26890851

  15. Increased expression and aberrant localization of mucin 13 in metastatic colon cancer.

    PubMed

    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; Chauhan, Subhash C

    2012-11-01

    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 (p<0.001) MUC13 expression in non-metastatic colon cancer samples compared with faint or very low expression in adjacent normal tissues. Interestingly, metastatic colon cancer and liver metastasis tissue samples demonstrated significantly (p<0.05) higher cytoplasmic and nuclear MUC13 expression compared with non-metastatic colon 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.

  16. Three cases of endoscopic resection for synchronous early colon cancers after self-expandable metallic stent placement for obstructive colon cancer

    PubMed Central

    Moroi, Rintaro; Endo, Katsuya; Ichikawa, Ryo; Takahashi, So; Shiroki, Takeharu; Shinkai, Hirohiko; Ishiyama, Fumitake; Kayaba, Shoichi

    2016-01-01

    Background and study aims: The feasibility of endoscopic resection for synchronous early colon cancer after placement of self-expandable metallic stents (SEMS) for malignant colorectal obstruction is unknown. Herein we evaluated 3 cases of endoscopic resection for synchronous early colorectal cancers after SEMS placement. Patient 1 was an 82-year-old man with obstructive sigmoid colon cancer. We curatively treated the synchronous descending colon cancer with endoscopic submucosal dissection (ESD) and the rectal cancer with endoscopic mucosal resection (EMR) after SEMS placement. This is the first reported case of a successful ESD for synchronous early colon cancer via the use of a colonic stent. Patient 2 was an 81-year-old man with obstructive ascending colon cancer. We resected the synchronous transverse colon cancer via ESD. Histologic findings indicated that the carcinoma cells had invaded the submucosal layer. Therefore, we immediately performed expanded right-hemicolectomy. Patient 3 was an 81-year-old man with obstructive sigmoid colon cancer. We curatively treated the synchronous transverse colon cancer with EMR after SEMS placement. There were no complications associated with the endoscopic treatments in any of the cases. Our results indicate that preoperative endoscopic resection combined with the ESD technique for synchronous colorectal cancer after SEMS placement could be effective as a surgical strategy for patients with malignant colorectal obstruction. PMID:27652303

  17. Dietary fibre and colon cancer: epidemiologic and experimental evidence.

    PubMed Central

    Reddy, B S

    1980-01-01

    Epidemiologic studies have identified two dietary factors, a relatively high intake of fat and a relatively low intake of fibre, that are associated with colon cancer in humans. However, a recent study has shown a low risk of large bowel cancer in a rural Finnish population with a high dietary intake of fat, but also a high intake of fibre. Observations in humans and studies in animals have indicated that dietary fibre may protect against colon carcinogenesis by binding bile acids in the intestinal tract, by a direct effect on the colonic mucosa and by an indirect effect on the metabolism of carcinogens. The strength of protection varies with the type of fibre. PMID:6254626

  18. Effect of misclassified underlying cause of death on survival estimates of colon and rectal cancer.

    PubMed

    Yin, Daixin; Morris, Cyllene R; Bates, Janet H; German, Robert R

    2011-07-20

    Inaccurate coding of patients' Underlying Cause of Death (UCOD) has constrained cause-specific survival estimates for colon and rectal cancers. Using California data from the Accuracy of Cancer Mortality study, we compared the cancer site data from the California Cancer Registry (CCR) with UCODs reported on death certificates and reclassified the UCODs based on cancer registry data when they disagreed. We then calculated 1-, 3-, 5-, and 10-year cause-specific survival for colon and rectal cancers separately, before and after the reclassification. Records from 26 312 colon and 10 687 rectal cancer patients were examined. UCOD records disagreed with CCR records for 700 (6%) of 11 404 colon cancer deaths and with 1958 (39%) of 5011 rectal cancer deaths, and 82% of the misclassified rectal cancer deaths were coded as colon cancer deaths in the UCOD. Reclassification decreased cause-specific survival for both colon and rectal cancers, but the impact was more pronounced for rectal cancer (eg, 5-year cause-specific survival of colon cancer decreased by 2.8% and of rectal cancer decreased by 20.0% relative to previous estimates; absolute rates changed from 65.4% to 63.6%, and 81.2% to 64.9%, respectively, after reclassification). Interchangeable use of the terms colon cancer and colorectal cancer is likely to be one of the reasons for UCOD misclassification. Educational measures could improve the accuracy of UCOD for colon and rectal cancer deaths.

  19. Mechanisms linking dietary fiber, gut microbiota and colon cancer prevention

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many epidemiological and experimental studies have suggested that dietary fiber plays an important role in colon cancer prevention. These findings may relate to the ability of fiber to reduce the contact time of carcinogens within the intestinal lumen and to promote healthy gut microbiota, which mod...

  20. Streptococcus intermedius liver abscesses and colon cancer: a case report.

    PubMed

    Millichap, J J; McKendrick, A I; Drelichman, V S

    2005-10-01

    Certain species of bacteria are known to be associated with colorectal cancer. We report a case of adenocarcinoma of the colon with bacteraemia and liver abscesses due to Streptococcus intermedius. The isolation of this organism should prompt investigation for colorectal neoplasm, which may be present but asymptomatic, without metastases, and therefore at a curative stage.

  1. Potentiation of Colon Cancer Susceptibility in Mice by Colonic Epithelial PPAR-δ/β Overexpression

    PubMed Central

    2014-01-01

    Background The nuclear receptor peroxisome proliferator-activated receptor-δ/β (PPAR-d) is upregulated in human colorectal cancers, but its role in colonic tumorigenesis remains controversial. Methods We generated a novel mouse model of intestinally targeted PPAR-d overexpression to simulate PPAR-d upregulation in human colon carcinogenesis. Colon-specific PPAR-d overexpression was confirmed by real-time reverse transcription polymerase chain reaction, immunoblotting, and activity assays. Mice with and without targeted PPAR-d overexpression were tested for azoxymethane (AOM)–induced colonic tumorigenesis. Mouse whole-genome transcriptome microarray analyses were performed to identify PPAR-d target genes to promote tumorigenesis. We used linear models to test for PPAR-d overexpression trend effects on tumor multiplicity. All statistical tests were two-sided. Results Targeted PPAR-d overexpression markedly increased colonic tumor incidence (from 0 of 10 wild-type [WT] littermate mice to 9 of 10 mice [P < .001] in 2 FVB/N background mouse lines [villin-PPAR-d-1 and villin-PPAR-d-2] at a 5-mg/kg AOM dose) and multiplicity (number of tumors per mouse per mg/kg dose of AOM increased from 0.47 [95% confidence interval [CI] = 0.22 to 0.72] for the WT littermates to 2.15 [95% CI = 1.90 to 2.40] [P < .001] for the villin-PPAR-d-1 mice and from 0.44 [95% CI = 0.09 to 0.79] for the WT littermates to 1.91 [95% CI = 1.57 to 2.25] [P < .001] for the villin-PPAR-d-2 mice). PPAR-d overexpression reversed resistance to AOM-induced colonic tumorigenesis in C57BL/6 mice. PPAR-d overexpression modulated expression of several novel PPAR-d target genes in normal-appearing colonic epithelial cells of mice with PPAR-d overexpression in a pattern that matched the changes in colonic tumors. Conclusions Our finding that PPAR-d upregulation profoundly enhances susceptibility to colonic tumorigenesis should impact the development of strategies of molecularly targeting PPAR-d in cancer and

  2. Active Surveillance for Prostate Cancer: Contemporary State of Practice

    PubMed Central

    Tosoian, Jeffrey J.; Carter, H. Ballentine; Lepor, Abbey; Loeb, Stacy

    2016-01-01

    Prostate cancer remains among the most commonly diagnosed malignancies worldwide. Early diagnosis and curative treatment appear to improve survival in men with unfavorable-risk cancers, but significant concerns exist regarding the overdiagnosis and overtreatment of men with lower-risk cancers. To this end, active surveillance (AS) has emerged as a primary management strategy in men with favorable-risk disease, and contemporary data suggest that use of AS has increased worldwide. Although published surveillance cohorts differ by protocol, reported rates of metastatic disease and prostate cancer-specific mortality are exceedingly low in the intermediate term (5–10 years). Such outcomes appear to be closely associated with program-specific criteria for selection, monitoring, and intervention, suggesting that AS – like other management strategies – could be individualized based on the level of risk acceptable to patients in light of personal preferences. Additional data are needed to better establish the risks associated with AS and to identify patient-specific characteristics that could modify prognosis. PMID:26954332

  3. Big data for population-based cancer research: the integrated cancer information and surveillance system.

    PubMed

    Meyer, Anne-Marie; Olshan, Andrew F; Green, Laura; Meyer, Adrian; Wheeler, Stephanie B; Basch, Ethan; Carpenter, William R

    2014-01-01

    The Integrated Cancer Information and Surveillance System (ICISS) facilitates population-based cancer research by developing extensive information technology systems that can link and manage large data sets. Taking an interdisciplinary 'team science' approach, ICISS has developed data, systems, and methods that allow researchers to better leverage the power of big data to improve population health.

  4. Colon Cancer Staging in Vulnerable Older Adults: Adherence to National Guidelines and Impact on Survival

    PubMed Central

    Leal, TB; Holden, T; Cavalcante, L; Allen, GO; Schumacher, JR; Smith, MA; Weiss, JM; Neuman, HB; LoConte, NK

    2015-01-01

    Background There is concern that elders are not adequately evaluated prior to colon cancer surgery. We sought to determine adherence with ACOVE-3 (Assessing Care of Vulnerable Elders) quality indicators for pre-operative staging prior to colectomy for colon cancer utilizing the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database (1992–2005). Methods We determined the proportion of patients aged 75 and older who had preoperative staging prior to colectomy for colon adenocarcinoma. Preoperative staging was defined as abdominopelvic computed tomography or magnetic resonance imaging scan (SCAN) and colonoscopy or flexible sigmoidoscopy (SCOPE). Multivariate logistic regression identified predictors of adherence. Odds ratios were adjusted for comorbidity, socioeconomic status, and disease severity. The association of adherence to ACOVE-3 and survival was quantified. Results Of the 37,862 patients, the majority were 75–84 years, 28% of the patients were ≥85 years. Regarding preoperative staging in the 6-month interval prior to surgical resection, 8% had neither SCAN nor SCOPE, 6% had only SCAN, 43% had only SCOPE, and 43% had both SCAN and SCOPE. Compared to patients who were not staged, those evaluated with either SCOPE alone or SCAN plus SCOPE had lower odds of 3-year mortality. Patients who were staged with SCAN alone had an increased odds of death compared to those who had neither SCAN or SCOPE. Conclusions These data demonstrate that the majority of vulnerable elders with colon cancer did not receive appropriate preoperative staging prior to resection. The findings also confirm that adherence to ACOVE-3 guidelines is associated with improved long-term survival. PMID:25914900

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

    PubMed

    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.

  6. Colon cancer proliferating desulfosinigrin in wasabi (Wasabia japonica).

    PubMed

    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.

  7. Treatment Options (by Stage) for Colon Cancer

    MedlinePlus

    ... Cancer.gov on the Managing Cancer Care page. Contact Us More information about contacting us or receiving ... Facebook Twitter Instagram YouTube Google+ LinkedIn GovDelivery RSS CONTACT INFORMATION Contact Us LiveHelp Online Chat MORE INFORMATION ...

  8. Eugenia jambolana (Java Plum) Fruit Extract Exhibits Anti-Cancer Activity against Early Stage Human HCT-116 Colon Cancer Cells and Colon Cancer Stem Cells

    PubMed Central

    Charepalli, Venkata; Reddivari, Lavanya; Vadde, Ramakrishna; Walia, Suresh; Radhakrishnan, Sridhar; Vanamala, Jairam K. P

    2016-01-01

    The World Health Organization predicts over a 70% increase in cancer incidents in developing nations over the next decade. Although these nations have limited access to novel therapeutics, they do have access to foods that contain chemopreventive bioactive compounds such as anthocyanins, and as such, consumption of these foods can be encouraged to combat cancer. We and others have previously characterized the anti-colon cancer properties of dietary anthocyanins from different sources. Eugenia jambolana (Java plum) is a tropical medicinal fruit rich in anthocyanins, however, its anti-colon cancer properties are not well characterized. Furthermore, recent evidence suggests that colon cancer stem cells (colon CSCs) promote resistance to chemotherapy, relapse of tumors and contribute to poor prognosis. The objectives of this study were to 1) characterize the anthocyanin profile of Java plum using HPLC-MS; and 2) determine the anti-proliferative (cell counting and MTT) and pro-apoptotic (TUNEL and caspase 3/7 glo assay) properties of Java plum fruit extract (JPE) using HCT-116 colon cancer cell line and colon CSCs (positive for CD 44, CD 133 and ALDH1b1 markers). HPLC-MS analysis showed that JPE contains a variety of anthocyanins including glucosides of delphinidin, cyanidin, petunidin, peonidin and malvidin. JPE anthocyanins suppressed (p < 0.05) proliferation in HCT-116 cells and elevated (p < 0.05) apoptosis in both HCT-116 cells and colon CSCs. JPE also suppressed the stemness in colon CSCs as evaluated using colony formation assay. These results warrant further assessment of the anti-cancer activity of JPE, and its molecular mechanisms using pre-clinical models of colon cancer. PMID:26927179

  9. Walnut Phenolic Extract and Its Bioactive Compounds Suppress Colon Cancer Cell Growth by Regulating Colon Cancer Stemness

    PubMed Central

    Lee, Jisoo; Kim, Yoo-Sun; Lee, JaeHwan; Heo, Seung Chul; Lee, Kook Lae; Choi, Sang-Woon; Kim, Yuri

    2016-01-01

    Walnut has been known for its health benefits, including anti-cardiovascular disease and anti-oxidative properties. However, there is limited evidence elucidating its effects on cancer stem cells (CSCs) which represent a small subset of cancer cells that provide resistance against chemotherapy. This study aimed to evaluate the anti-CSCs potential of walnut phenolic extract (WPE) and its bioactive compounds, including (+)-catechin, chlorogenic acid, ellagic acid, and gallic acid. In the present study, CD133+CD44+ cells were isolated from HCT116 cells using fluorescence-activated cell sorting (FACS) and then treated with WPE. As a result, survival of the CD133+CD44+ HCT116 cells was inhibited and cell differentiation was induced by WPE. In addition, WPE down-regulated the CSC markers, CD133, CD44, DLK1, and Notch1, as well as the β-catenin/p-GSK3β signaling pathway. WPE suppressed the self-renewal capacity of CSCs. Furthermore, the WPE exhibited stronger anti-CSC effects than its individual bioactive compounds. Finally, the WPE inhibited specific CSC markers in primary colon cancer cells isolated from primary colon tumor. These results suggest that WPE can suppress colon cancer by regulating the characteristics of colon CSCs. PMID:27455311

  10. Walnut Phenolic Extract and Its Bioactive Compounds Suppress Colon Cancer Cell Growth by Regulating Colon Cancer Stemness.

    PubMed

    Lee, Jisoo; Kim, Yoo-Sun; Lee, JaeHwan; Heo, Seung Chul; Lee, Kook Lae; Choi, Sang-Woon; Kim, Yuri

    2016-07-21

    Walnut has been known for its health benefits, including anti-cardiovascular disease and anti-oxidative properties. However, there is limited evidence elucidating its effects on cancer stem cells (CSCs) which represent a small subset of cancer cells that provide resistance against chemotherapy. This study aimed to evaluate the anti-CSCs potential of walnut phenolic extract (WPE) and its bioactive compounds, including (+)-catechin, chlorogenic acid, ellagic acid, and gallic acid. In the present study, CD133⁺CD44⁺ cells were isolated from HCT116 cells using fluorescence-activated cell sorting (FACS) and then treated with WPE. As a result, survival of the CD133⁺CD44⁺ HCT116 cells was inhibited and cell differentiation was induced by WPE. In addition, WPE down-regulated the CSC markers, CD133, CD44, DLK1, and Notch1, as well as the β-catenin/p-GSK3β signaling pathway. WPE suppressed the self-renewal capacity of CSCs. Furthermore, the WPE exhibited stronger anti-CSC effects than its individual bioactive compounds. Finally, the WPE inhibited specific CSC markers in primary colon cancer cells isolated from primary colon tumor. These results suggest that WPE can suppress colon cancer by regulating the characteristics of colon CSCs.

  11. Obstructive Left Colon Cancer Should Be Managed by Using a Subtotal Colectomy Instead of Colonic Stenting

    PubMed Central

    Min, Chung Ki; Lee, Donghyoun; Jung, Kyung Uk; Lee, Sung Ryol; Kim, Hungdai; Chun, Ho-Kyung

    2016-01-01

    Purpose This study compared a subtotal colectomy to self-expandable metallic stent (SEMS) insertion as a bridge to surgery for patients with left colon-cancer obstruction. Methods Ninety-four consecutive patients with left colon-cancer obstruction underwent an emergency subtotal colectomy or elective SEMS insertion between January 2007 and August 2014. Using prospectively collected data, we performed a retrospective comparative analysis on an intention-to-treat basis. Results A subtotal colectomy and SEMS insertion were attempted in 24 and 70 patients, respectively. SEMS insertion technically failed in 5 patients (7.1%). The mean age and rate of obstruction in the descending colon were higher in the subtotal colectomy group than the SEMS group. Sex, underlying disease, American Society of Anesthesiologists physical status, and pathological stage showed no statistical difference. Laparoscopic surgery was performed more frequently in patients in the SEMS group (62 of 70, 88.6%) than in patients in the subtotal colectomy group (4 of 24, 16.7%). The overall rate of postoperative morbidity was higher in the SEMS group. No Clavien-Dindo grade III or IV complications occurred in the subtotal colectomy group, but 2 patients (2.9%) died from septic complications in the SEMS group. One patient (4.2%) in the subtotal colectomy group had synchronous cancer. The total hospital stay was shorter in the subtotal colectomy group. The median number of bowel movements in the subtotal colectomy group was twice per day at postoperative 3–6 months. Conclusion A subtotal colectomy for patients with obstructive left-colon cancer is a clinically and oncologically safer, 1-stage, surgical strategy compared to SEMS insertion as a bridge to surgery. PMID:28119864

  12. Functional and genetic analysis of the colon cancer network.

    PubMed

    Emmert-Streib, Frank; de Matos Simoes, Ricardo; Glazko, Galina; McDade, Simon; Haibe-Kains, Benjamin; Holzinger, Andreas; Dehmer, Matthias; Campbell, Frederick

    2014-01-01

    Cancer is a complex disease that has proven to be difficult to understand on the single-gene level. For this reason a functional elucidation needs to take interactions among genes on a systems-level into account. In this study, we infer a colon cancer network from a large-scale gene expression data set by using the method BC3Net. We provide a structural and a functional analysis of this network and also connect its molecular interaction structure with the chromosomal locations of the genes enabling the definition of cis- and trans-interactions. Furthermore, we investigate the interaction of genes that can be found in close neighborhoods on the chromosomes to gain insight into regulatory mechanisms. To our knowledge this is the first study analyzing the genome-scale colon cancer network.

  13. Correlation of trace elements in hair with colon cancer

    SciTech Connect

    Kwiatek, W.M.; Cholewa, M.; Kajfosz, J.; Jones, K.W.; Shore, R.E.; Redrick, A.L.

    1986-01-01

    The trace element content of 116 hair samples from patients with colon cancer and from referent series of patients who had a variety of other diseases were measured using proton-induced x-ray emission (PIXE). The patients had been on largely uncontrolled diets, and the interest was whether there were differences in trace element concentrations attributable to the effects of colon cancer. The concentrations of K, Ca, Mn, Fe, Cu, Zn, Se, Br, and Rb were determined using a beam of 2.5-MeV protons. Minimum detectable limits (MDL) of 0.3 ppM were obtained for Zn and Se. Cluster analysis of the data set did not reveal any significant differences between the cancer and control groups. Mean values and ranges obtained for the elemental concentrations show good agreement with other published determinations. 20 refs., 3 figs., 3 tabs.

  14. Takotsubo Cardiomyopathy in a Patient with Undiscovered Sigmoid Colon Cancer

    PubMed Central

    2017-01-01

    Takotsubo cardiomyopathy (TTC) is a stress-related cardiomyopathy that is characterized by reversible left systolic dysfunction, which appears to be precipitated by sudden emotional or physical stress in the absence of myocardial infarction. Here we present a rare case that clinically presented with intermittent abdominal pain, initially impressed as non-ST elevation myocardial infarction and congestive heart failure but with a normal coronary angiogram. Her symptoms relieved spontaneously without returning. Sigmoid colon cancer was diagnosed via colonoscopy later due to persistent abdominal discomfort. In the absence of detectable emotional or physical stress factors, the newly diagnosed sigmoid colon cancer was the only possible trigger factor of TTC. We offer this case as a reminder that cancer should be considered in the differential diagnosis of patients presenting with the etiology of TTC. PMID:28377824

  15. Methylselenol, a selenium metabolite, plays common and different roles in cancerous colon HCT116 cell and noncancerous NCM460 colon cell proliferation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Methylselenol has been hypothesized to be a critical selenium (Se) metabolite for anticancer activity in vivo. To determine differential chemopreventive effects of methylselenol on colon cancer cells versus colon noncancerous cells, colon-cancer-derived HCT-116 cells and noncancerous colonic NCM460 ...

  16. Colon cancer stem cells: promise of targeted therapy.

    PubMed

    Todaro, Matilde; Francipane, Maria Giovanna; Medema, Jan Paul; Stassi, Giorgio

    2010-06-01

    First developed for hematologic disorders, the concept of cancer stem cells (CSCs) was expanded to solid tumors, including colorectal cancer (CRC). The traditional model of colon carcinogenesis includes several steps that occur via mutational activation of oncogenes and inactivation of tumor suppressor genes. Intestinal epithelial cells exist for a shorter amount of time than that required to accumulate tumor-inducing genetic changes, so researchers have investigated the concept that CRC arises from the long-lived stem cells, rather than from the differentiated epithelial cells. Colon CSCs were originally identified through the expression of the CD133 glycoprotein using an antibody directed to its epitope AC133. It is not clear if CD133 is a marker of colon CSCs-other cell surface markers, such as epithelial-specific antigen, CD44, CD166, Musashi-1, CD29, CD24, leucine-rich repeat-containing G-protein-coupled receptor 5, and aldehyde dehydrogenase 1, have been proposed. In addition to initiating and sustaining tumor growth, CSCs are believed to mediate cancer relapse after chemotherapy. How can we identify and analyze colon CSCs and what agents are being designed to kill this chemotherapy-refractory population?

  17. Biomarkers for detection and surveillance of bladder cancer

    PubMed Central

    Budman, Lorne I; Kassouf, Wassim; Steinberg, Jordan R

    2008-01-01

    Introduction Bladder cancer is the fourth most common cancer in men and the ninth most common cancer in women in Canada. Early detection of tumours is essential for improved prognosis and long-term survival. The standard method for detection and surveillance is cystoscopy together with urine cytology. Cystoscopy is relatively sensitive but is expensive and invasive. Urinary cytology is a noninvasive method that has poor sensitivity but high specificity; it is relied on for the detection of carcinoma in situ. Currently, several urinary-based bladder tumour biomarkers with USFDA/Health Canada approval are available commercially, but none have been widely adopted by urologists despite their offering high sensitivity and/or specificity. We present here a review of recent studies evaluating 7 commercial biomarker assays for the detection and/or surveillance of bladder cancer. Results Sensitivity and specificity ranges, respectively, for each marker were reported as follows: BTA Stat (Polymedco), 52.5%–78.0% and 69.0%–87.1%; BTA Trak (Polymedco), 51%–100% and 73%–92.5%; cytology, 12.1%–84.6% and 78.0%–100%; hematuria dipstick, 47.0%–92.6% and 51.0%–84.0%; NMP22 Bladder Cancer Test (Matritech), 34.6%–100% and 60.0%–95.0%; NMP22 BladderChek (Matritech), 49.5%–65.0% and 40.0%–89.8%; ImmunoCyt/uCyt+ (DiagnoCure), 63.3%–84.9% and 62.0%–78.1%; ImmunoCyt/uCyt+ and cytology, 81.0%–89.3% and 61.0%–77.7%; and UroVysion (Abbott Molecular)/florescence in situ hybridization, 68.6%–100% and 65.0%–96.0%. Conclusion We find that no currently available bladder cancer urinary marker is sensitive enough to eliminate the need for cystoscopy. In addition, cytology remains integral to the detection of occult cancer. However, owing to their relatively high sensitivities, these markers may be used to extend the period between cystoscopies in the surveillance of patients with transitional cell carcinoma. Further study is required to determine which markers

  18. Fulminant abdominal gas gangrene in metastatic colon cancer.

    PubMed

    Bozkurt, Mustafa; Okutur, Kerem; Aydin, Kübra; Namal, Esat; Oztürk, Akin; Balci, Cem; Demir, Gökhan

    2012-02-01

    We report a case of fulminant abdominal gas gangrene in a patient with metastatic colon cancer. A 39-year-old patient with descending colon, high-grade adenocarcinoma and coexisting liver and lymph node metastases received two courses of chemotherapy. The patient developed sudden acute abdominal symptoms accompanied by septic shock parameters. The imaging findings on computed tomography were characteristic for abdominal gas gangrene, involving liver metastases, portal vein and lymph nodes with associated pneumoperitoneum. The patient succumbed to the disease within hours following the onset of symptoms.

  19. Radioimmunoguided surgery in primary colon cancer

    SciTech Connect

    Nieroda, C.A.; Mojzisik, C.; Sardi, A.; Ferrara, P.J.; Hinkle, G.; Thurston, M.O.; Martin, E.W. Jr. )

    1990-01-01

    Radioimmunoguided surgery (RIGS), the intraoperative use of a hand-held gamma detecting probe (GDP) to identify tissue containing radiolabeled monoclonal antibody (MAb), was performed upon 30 patients with primary colon carcinoma. Each patient received an intravenous injection of MAb B72.3 (1.0 to 0.25 mg) radiolabeled with {sup 125}I (5.0 to 1.0 mCi) 8 to 34 days before exploration. The GDP was used to measure radioactivity in colon tissue, tumor bed, nodal drainage areas, and areas of suspected metastases. Antibody localized to histologically documented tumor in 23 of 30 patients (77%). Tumor margins were more clearly defined in 20 of 30 patients (67%). GDP counts led to major alterations in surgical resection in five patients (17%) and changes in adjuvant therapy in four (14%). GDP counts identified occult liver metastases in two patients (7%) and correctly indicated the benign nature of liver masses in three (10%). In four patients (13%), occult nodal metastases were identified. RIGS can precisely delineate tumor margins, define the extent of nodal involvement, and localize occult tumor, providing a method of immediate intraoperative staging that may lessen recurrences and produce higher survival rates.

  20. Fragmentation in specialist care and stage III colon cancer

    PubMed Central

    Hussain, Tanvir; Chang, Hsien-Yen; Veenstra, Christine M.; Pollack, Craig Evan

    2015-01-01

    Background Patients with cancer frequently transition between different types of specialists and across care settings. We explored how frequently the medical and surgical oncologic care of stage III colon cancer patients occurs across more than one hospital and whether this is associated with mortality and costs. Methods This is a retrospective SEER-Medicare cohort study of 9,075 stage III colon cancer patients diagnosed between 2000 and 2009 receiving both surgical and medical oncologic care within one year of diagnosis. Patients were assigned to the hospital where they had their cancer surgery and to their oncologist's primary hospital, and then characterized according to whether these hospitals were same or different. Outcomes included all-cause mortality, subhazards for colon cancer specific mortality, and cost of care at 12 months. Results 37% of patients received their surgical and medical oncologic care from different hospitals. Rural patients were less likely than urban patients to receive medical oncologic care from the same hospital (OR 0.62, 95%CI 0.43-0.90). Care from the same hospital was not associated with reduced all-cause or colon cancer specific mortality but resulted in lower costs at 12 months (dollars saved $5493, 95%CI $1799, $9525), 8% of median cost. Conclusions Delivery of surgical and medical oncology care at the same hospital was associated with lower costs; however, reforms which seek to improve outcomes and cost through integrating complex care will need to address the significant proportion of patients receiving care across more than one hospital. PMID:26043368

  1. A case of leptospirosis simulating colon cancer with liver metastases

    PubMed Central

    Granito, Alessandro; Ballardini, Giorgio; Fusconi, Marco; Volta, Umberto; Muratori, Paolo; Sambri, Vittorio; Battista, Giuseppe; Bianchi, Francesco B.

    2004-01-01

    We report a case of a 61-year-old man who presented with fatigue, abdominal pain and hepatomegaly. Computed tomography (CT) of the abdomen showed hepatomegaly and multiple hepatic lesions highly suggestive of metastatic diseases. Due to the endoscopic finding of colon ulcer, colon cancer with liver metastases was suspected. Biochemically a slight increase of transaminases, alkaline phosphatase and gammaglutamyl transpeptidase were present; α - fetoprotein, carcinoembryogenic antigen and carbohydrate 19-9 antigen serum levels were normal. Laboratory and instrumental investigations, including colon and liver biopsies revealed no signs of malignancy. In the light of spontaneous improvement of symptoms and CT findings, his personal history was revaluated revealing direct contact with pigs and their tissues. Diagnosis of leptospirosis was considered and confirmed by detection of an elevated titer of antibodies to leptospira. After two mo, biochemical data, CT and colonoscopy were totally normal. PMID:15285043

  2. Surgical Treatment of Colon Cancer in Patients Eighty Years of Age and Older: Analysis of 31,574 Patients in the SEER-Medicare Database

    PubMed Central

    Neuman, Heather B.; O’Connor, Erin S.; Weiss, Jennifer; LoConte, Noelle K.; Greenblatt, David Y.; Greenberg, Caprice C.; Smith, Maureen A.

    2012-01-01

    Background Age-related disparities in colon cancer treatment exist, with older patients less likely to receive recommended therapy. However, few studies have focused on receipt of surgery. The objective was to describe patterns of surgery in colon cancer patients ≥80 years and examine outcomes with and without colectomy. Methods Medicare beneficiaries ≥80 years with colon cancer diagnosed from 1992–2005 were identified from the Surveillance, Epidemiology and End Results- Medicare database. Multivariable logistic regression analysis was utilized to assess factors associated with non-operative management. Kaplan-Meier survival analysis determined one-year overall and colon cancer-specific survival. Results Of 31,574 patients, 80% underwent colectomy. 46% occurred during an urgent/emergent admission, with decreased 1-year overall survival (70% vs. 86% during an elective admission). Factors most predictive of non-operative management include older age, black race, more hospital admissions, use of home oxygen, use of a wheel chair, being frail and dementia. For both operative and non-operative patients, one-year overall survival was lower than colon cancer-specific survival (colectomy 78% vs. 89%; no colectomy 58% vs. 78%). Conclusions Most older colon cancer patients are receiving surgery, with improved outcomes compared to non-operative management. However, many patients not selected for surgery die of unrelated causes, reflecting good surgical selection. Patients undergoing surgery during an urgent/emergent admission have an increased short-term mortality. As earlier detection of colon cancer may increase the proportion of older patients undergoing elective surgery, these findings have policy implications for colon cancer screening and suggest that age should not be the only factor driving cancer screening recommendations. PMID:22893570

  3. Stenting for Obstructing Colon Cancer: Fewer Complications and Colostomies

    PubMed Central

    Miller, Peter; Goldstein, Rachel; Coury, Joseph; Hackford, Alan; Dao, Haisar

    2015-01-01

    Background and Objectives: Colonic stenting has been used in the setting of malignant obstruction to avoid an emergent colectomy. We sought to determine whether preoperative placement of a colonic stent decreases morbidity and the rate of colostomy formation. Methods: Cases of obstructing sigmoid, rectosigmoid, and rectal cancer from January 1, 2010, to December 31, 2011, were identified in the Nationwide Inpatient Sample (NIS) database. All patients were treated at hospitals in the United States, and the database generated national estimates. Postoperative complications, mortality, and the rate of colostomy formation were analyzed. Results: Of the estimated 7891 patients who presented with obstructing sigmoid, rectosigmoid, or rectal cancer necessitating intervention, 12.1% (n = 956) underwent placement of a colonic stent, and the remainder underwent surgery without stent placement. Of the patients who underwent stenting, 19.9% went on to have colon resection or stoma creation during the same admission. Patients who underwent preoperative colonic stent placement had a lower rate of total postoperative complications (10.5% vs 21.7%; P < .01). There was no significant difference in mortality (4.7% vs 4.2%; P = .69). The rate of colostomy formation was more than 2-fold higher in patients who did not undergo preoperative stenting (42.5% vs 19.5%; P < .01). Preoperative stenting was associated with increased use of laparoscopy (32.6% vs 9.7%; P < .01). Conclusions: Our study characterizes the national incidence of preoperative placement of a colonic stent in the setting of malignant obstruction. Preoperative stent placement is associated with lower postoperative complications and a lower rate of colostomy formation. The results support the hypothesis that stenting as a bridge to surgery may benefit patients by converting an emergent surgery into an elective one. PMID:25848200

  4. Use of Aspirin postdiagnosis improves survival for colon cancer patients

    PubMed Central

    Bastiaannet, E; Sampieri, K; Dekkers, O M; de Craen, A J M; van Herk-Sukel, M P P; Lemmens, V; van den Broek, C B M; Coebergh, J W; Herings, R M C; van de Velde, C J H; Fodde, R; Liefers, G J

    2012-01-01

    Background: The preventive role of non-steroid anti-inflammatory drugs (NSAIDs) and aspirin, in particular, on colorectal cancer is well established. More recently, it has been suggested that aspirin may also have a therapeutic role. Aim of the present observational population-based study was to assess the therapeutic effect on overall survival of aspirin/NSAIDs as adjuvant treatment used after the diagnosis of colorectal cancer patients. Methods: Data concerning prescriptions were obtained from PHARMO record linkage systems and all patients diagnosed with colorectal cancer (1998–2007) were selected from the Eindhoven Cancer Registry (population-based cancer registry). Aspirin/NSAID use was classified as none, prediagnosis and postdiagnosis and only postdiagnosis. Patients were defined as non-user of aspirin/NSAIDs from the date of diagnosis of the colorectal cancer to the date of first use of aspirin or NSAIDs and user from first use to the end of follow-up. Poisson regression was performed with user status as time-varying exposure. Results: In total, 1176 (26%) patients were non-users, 2086 (47%) were prediagnosis and postdiagnosis users and 1219 (27%) were only postdiagnosis users (total n=4481). Compared with non-users, a survival gain was observed for aspirin users; the adjusted rate ratio (RR) was 0.77 (95% confidence interval (CI) 0.63–0.95; P=0.015). Stratified for colon and rectal, the survival gain was only present in colon cancer (adjusted RR 0.65 (95%CI 0.50–0.84; P=0.001)). For frequent users survival gain was larger (adjusted RR 0.61 (95%CI 0.46–0.81; P=0.001). In rectal cancer, aspirin use was not associated with survival (adjusted RR 1.10 (95%CI 0.79–1.54; P=0.6). The NSAIDs use was associated with decreased survival (adjusted RR 1.93 (95%CI 1.70–2.20; P<0.001). Conclusion: Aspirin use initiated or continued after diagnosis of colon cancer is associated with a lower risk of overall mortality. These findings strongly support initiation of

  5. Identifying molecular targets of lifestyle modifications in colon cancer prevention.

    PubMed

    Derry, Molly M; Raina, Komal; Agarwal, Chapla; Agarwal, Rajesh

    2013-01-01

    One in four deaths in the United States is cancer-related, and colorectal cancer (CRC) is the second leading cause of cancer-associated deaths. Screening strategies are utilized but have not reduced disease incidence or mortality. In this regard, there is an interest in cancer preventive strategies focusing on lifestyle intervention, where specific etiologic factors involved in cancer initiation, promotion, and progression could be targeted. For example, exposure to dietary carcinogens, such as nitrosamines and polycyclic aromatic hydrocarbons influences colon carcinogenesis. Furthermore, dietary deficiencies could alter sensitivity to genetic damage and influence carcinogen metabolism contributing to CRC. High alcohol consumption increases the risk of mutations including the fact that acetaldehyde, an ethanol metabolite, is classified as a group 1 carcinogen. Tobacco smoke exposure is also a risk factor for cancer development; approximately 20% of CRCs are associated with smoking. Additionally, obese patients have a higher risk of cancer development, which is further supported by the fact that physical activity decreases CRC risk by 55%. Similarly, chronic inflammatory conditions also increase the risk of CRC development. Moreover, the circadian clock alters digestion and regulates other biochemical, physiological, and behavioral processes that could influence CRC. Taken together, colon carcinogenesis involves a number of etiological factors, and therefore, to create effective preventive strategies, molecular targets need to be identified and beleaguered prior to disease progression. With this in mind, the following is a comprehensive review identifying downstream target proteins of the above lifestyle risk factors, which are modulated during colon carcinogenesis and could be targeted for CRC prevention by novel agents including phytochemicals.

  6. Identifying Molecular Targets of Lifestyle Modifications in Colon Cancer Prevention

    PubMed Central

    Derry, Molly M.; Raina, Komal; Agarwal, Chapla; Agarwal, Rajesh

    2013-01-01

    One in four deaths in the United States is cancer-related, and colorectal cancer (CRC) is the second leading cause of cancer-associated deaths. Screening strategies are utilized but have not reduced disease incidence or mortality. In this regard, there is an interest in cancer preventive strategies focusing on lifestyle intervention, where specific etiologic factors involved in cancer initiation, promotion, and progression could be targeted. For example, exposure to dietary carcinogens, such as nitrosamines and polycyclic aromatic hydrocarbons influences colon carcinogenesis. Furthermore, dietary deficiencies could alter sensitivity to genetic damage and influence carcinogen metabolism contributing to CRC. High alcohol consumption increases the risk of mutations including the fact that acetaldehyde, an ethanol metabolite, is classified as a group 1 carcinogen. Tobacco smoke exposure is also a risk factor for cancer development; approximately 20% of CRCs are associated with smoking. Additionally, obese patients have a higher risk of cancer development, which is further supported by the fact that physical activity decreases CRC risk by 55%. Similarly, chronic inflammatory conditions also increase the risk of CRC development. Moreover, the circadian clock alters digestion and regulates other biochemical, physiological, and behavioral processes that could influence CRC. Taken together, colon carcinogenesis involves a number of etiological factors, and therefore, to create effective preventive strategies, molecular targets need to be identified and beleaguered prior to disease progression. With this in mind, the following is a comprehensive review identifying downstream target proteins of the above lifestyle risk factors, which are modulated during colon carcinogenesis and could be targeted for CRC prevention by novel agents including phytochemicals. PMID:23675573

  7. Increasing Breast Cancer Surveillance Among African American Breast Cancer Survivors

    DTIC Science & Technology

    2010-01-01

    one or both breasts were affected. Family Member (e.g. grandmother, aunt) Paternal or Maternal Type or Location of Cancer (e.g. breast...breast cancer who previously participated in an ongoing parent project and are at least 3 months post-treatment. Participants were to be assigned to... parent study also awaiting approval (“Behavior, Estrogen Metabolism, and Breast Cancer Risk: A Molecular Epidemiologic Study” HSRRB Log Number A

  8. Oncotype DX(®) colon cancer assay for prediction of recurrence risk in patients with stage II and III colon cancer: A review of the evidence.

    PubMed

    You, Y Nancy; Rustin, Rudolph B; Sullivan, James D

    2015-06-01

    Advances in molecular biology have enabled identification of tumor biomarkers that allow for individualized risk assessment for patients with cancer. Molecular predictors of clinical outcome can help inform discussion regarding the role of adjuvant chemotherapy in patients with resected colon cancer, such as those with stage II colon cancer in which the benefit of adjuvant therapy is controversial or those with stage III colon cancer who may have a lower risk of recurrence and less absolute benefit from oxaliplatin therapy. This article summarizes the data surrounding the development, validation, and clinical and economic utility of the Oncotype DX(®) colon cancer assay, a multigene expression assay validated to independently predict recurrence risk in patients with stage II and III colon cancer beyond traditional factors.

  9. Diet and colon cancer in Los Angeles County, California.

    PubMed

    Peters, R K; Pike, M C; Garabrant, D; Mack, T M

    1992-09-01

    The diets of 746 colon cancer cases in Los Angeles County, California (USA) were compared with those of 746 controls matched on age, sex, race, and neighborhood. In both genders, total energy intake was associated with significantly increased risk, and calcium intake was associated with significantly decreased risk. These effects were reduced only slightly after adjustment for the nondietary risk factors (weight, physical activity, family history, and, if female, pregnancy history). In men, total fat and alcohol intakes were responsible for the calorie effect; in women, no individual source of calories was associated independently with risk. Neither saturated fat nor fat from animal sources was responsible for the fat effect. There were no additional independent significant effects for sucrose, fiber, cruciferous vegetables, beta-carotene, other vitamins, or any other nutrient or micronutrient. In univariate analyses, meats, poultry, breads, and sweets were associated with excess risk, and yogurt was protective. After adjustment for sources of calories, no individual food was associated with excess risk, but yogurt remained significantly protective. Total calories were associated with excess risk throughout the colon while the effects of calcium, fat, and alcohol appeared somewhat stronger in the distal colon. After adjustment, crude fiber was significantly protective in the ascending colon but not even weakly protective in the distal colon.

  10. Streptococcus bovis endocarditis and colon cancer: myth or reality? A case report and literature review.

    PubMed

    Galdy, Salvatore; Nastasi, Giuseppe

    2012-12-05

    A relationship between infective endocarditis and colon cancer was established in 1950, and Streptococcus bovis was successfully isolated in 1970. However, this association and its pathogenesis still remain unclear. In this paper, we describe the clinical case of a patient with a history of colon cancer and infective endocarditis caused by Streptococcus bovis. The role of S bovis as an aetiological agent in the development of colon cancer is intriguing but uncertain. S bovis infection should be considered a silent sign of gastrointestinal malignancy or hepatic disease. We believe that in order to demonstrate the presence of colon cancer, all patients with S bovis infection require an endoscopic investigation of the colon.

  11. Clinical investigation of TROP-2 as an independent biomarker and potential therapeutic target in colon cancer.

    PubMed

    Zhao, Peng; Yu, Hai-Zheng; Cai, Jian-Hui

    2015-09-01

    Colon cancer is associated with a severe demographic and economic burden worldwide. The pathogenesis of colon cancer is highly complex and involves sequential genetic and epigenetic mechanisms. Despite extensive investigation, the pathogenesis of colon cancer remains to be elucidated. As the third most common type of cancer worldwide, the treatment options for colon cancer are currently limited. Human trophoblast cell‑surface marker (TROP‑2), is a cell‑surface transmembrane glycoprotein overexpressed by several types of epithelial carcinoma. In addition, TROP‑2 has been demonstrated to be associated with tumorigenesis and invasiveness in solid types of tumor. The aim of the present study was to investigate the protein expression of TROP‑2 in colon cancer tissues, and further explore the association between the expression of TROP‑2 and clinicopathological features of patients with colon cancer. The expression and localization of the TROP‑2 protein was examined using western blot analysis and immunofluorescence staining. Finally, the expression of TROP‑2 expression was correlated to conventional clinicopathological features of colon cancer using a χ2 test. The results revealed that TROP‑2 protein was expressed at high levels in the colon cancer tissues, which was associated with the development and pathological process of colon cancer. Therefore, TROP‑2 may be used as a biomarker to determine the clinical prognosis, and as a potential therapeutic target in colon cancer.

  12. Active surveillance for low-risk prostate cancer.

    PubMed

    Bangma, Chris H; Bul, Meelan; van der Kwast, Theo H; Pickles, Tom; Korfage, Ida J; Hoeks, Caroline M; Steyerberg, Ewout W; Jenster, Guido; Kattan, Michael W; Bellardita, Lara; Carroll, Peter R; Denis, Louis J; Parker, Chris; Roobol, Monique J; Emberton, Mark; Klotz, Laurence H; Rannikko, Antti; Kakehi, Yoshiyuki; Lane, Janet A; Schröder, Fritz H; Semjonow, Axel; Trock, Bruce J; Valdagni, Riccardo

    2013-03-01

    Active surveillance (AS) is an important management strategy for men diagnosed with low-risk prostate cancer (PCa). The need for AS is increasing due to the awareness that many PCa are identified that show a low growth potential and therefore are likely to remain clinically asymptomatic during the lifetime of an individual. Currently there is no good method to prevent the overdiagnosis of indolent cancers upfront. During the last decade, several studies on AS around the world have made observations that feed the discussion on how to select and monitor these patients, how to proceed with the research to develop a better and more precise clinical definition of indolent cancers and how to manage men under AS clinically. Furthermore, patients' perspectives have become clearer, and quality of life studies give direction to the practical approach and care for patients and partners. This paper reflects the consensus on the state of the art and the future direction of AS, based on the Inside Track Conference "Active Surveillance for low risk prostate cancer" (Chairmen: C.H. Bangma, NL, and L. Klotz, CA; Co-Chairmen: L.J. Denis, BE, and C. Parker, UK; Scientific Coordinators: M. J. Roobol, NL, and E.W. Steyerberg, NL), organized by the European School of Oncology in collaboration with Europa Uomo in Rotterdam, the Netherlands in January 2012. Topics for discussion were the optimisation of patient selection based on indolent disease definition, the incorporation of therapeutic agents into AS programs, the optimisation of patient care, and the application of emerging technologies and biomarkers.

  13. Increased transversions in a novel mutator colon cancer cell line.

    PubMed

    Eshleman, J R; Donover, P S; Littman, S J; Swinler, S E; Li, G M; Lutterbaugh, J D; Willson, J K; Modrich, P; Sedwick, W D; Markowitz, S D; Veigl, M L

    1998-03-05

    We describe a novel mutator phenotype in the Vaco411 colon cancer cell line which increases the spontaneous mutation rate 10-100-fold over background. This mutator results primarily in transversion base substitutions which are found infrequently in repair competent cells. Of the four possible types of transversions, only three were principally recovered. Spontaneous mutations recovered also included transitions and large deletions, but very few frameshifts were recovered. When compared to known mismatch repair defective colon cancer mutators, the distribution of mutations in Vaco411 is significantly different. Consistent with this difference, Vaco411 extracts are proficient in assays of mismatch repair. The Vaco411 mutator appears to be novel, and is not an obvious human homologue of any of the previously characterized bacterial or yeast transversion phenotypes. Several hypotheses by which this mutator may produce transversions are presented.

  14. Geographic Variation in Use of Laparoscopic Colectomy for Colon Cancer

    PubMed Central

    Reames, Bradley N.; Sheetz, Kyle H.; Waits, Seth A.; Dimick, Justin B.; Regenbogen, Scott E.

    2014-01-01

    Purpose Emerging evidence supporting the use of laparoscopic colectomy in patients with cancer has led to dramatic increases in utilization. Though certain patient and hospital characteristics may be associated with the use of laparoscopy, the influence of geography is poorly understood. Methods We used national Medicare claims data from 2009 and 2010 to examine geographic variation in utilization of laparoscopic colectomy for patients with colon cancer. Patients were assigned to hospital referral regions (HRRs) where they were treated. Multivariable logistic regression was used to generate age, sex, and race-adjusted rates of laparoscopic colectomy for each HRR. Patient quintiles of adjusted HRR utilization were used to evaluate differences in patient and hospital characteristics across low and high-utilizing HRRs. Results A total of 93,786 patients underwent colon resections at 3,476 hospitals during the study period, of which 30,502 (32.5%) were performed laparoscopically. Differences in patient characteristics between the lowest and highest quintiles of HRR utilization were negligible, and there was no difference in the availability of laparoscopic technology. Yet adjusted rates of laparoscopic colectomy utilization varied from 0% to 66.8% across 306 HRRs in the United States. Conclusion There is wide geographic variation in the utilization of laparoscopic colectomy for Medicare patients with colon cancer, suggesting treatment location may substantially influence a patient's options for surgical approach. Future efforts to reduce variation will require increased dissemination of training techniques, novel opportunities for learning among surgeons, and enhanced educational resources for patients. PMID:25287826

  15. Genomic era diagnosis and management of hereditary and sporadic colon cancer

    PubMed Central

    Esplin, Edward David; Snyder, Michael Paul

    2014-01-01

    The morbidity and mortality attributable to heritable and sporadic carcinomas of the colon are substantial and affect children and adults alike. Despite current colonoscopy screening recommendations colorectal adenocarcinoma (CRC) still accounts for almost 140000 cancer cases yearly. Familial adenomatous polyposis (FAP) is a colon cancer predisposition due to alterations in the adenomatous polyposis coli gene, which is mutated in most CRC. Since the beginning of the genomic era next-generation sequencing analyses of CRC continue to improve our understanding of the genetics of tumorigenesis and promise to expand our ability to identify and treat this disease. Advances in genome sequence analysis have facilitated the molecular diagnosis of individuals with FAP, which enables initiation of appropriate monitoring and timely intervention. Genome sequencing also has potential clinical impact for individuals with sporadic forms of CRC, providing means for molecular diagnosis of CRC tumor type, data guiding selection of tumor targeted therapies, and pharmacogenomic profiles specifying patient specific drug tolerances. There is even a potential role for genomic sequencing in surveillance for recurrence, and early detection, of CRC. We review strategies for diagnostic assessment and management of FAP and sporadic CRC in the current genomic era, with emphasis on the current, and potential for future, impact of genome sequencing on the clinical care of these conditions. PMID:25493239

  16. Isolated splenic metastasis from colon cancer: Case report

    PubMed Central

    Abdou, Jiddou; Omor, Youssef; Boutayeb, Saber; Elkhannoussi, Basma; Errihani, Hassan

    2016-01-01

    Isolated splenic metastases from colorectal cancer are very rare clinical entities and when they are present, they usually manifest widely disseminated disease. In this paper we report a case of metachronous solitary isolated splenic metastasis from colon cancer in a 64-year-old woman who was successfully treated by laparoscopic splenectomy. We discuss the pathological and clinical aspects of this condition. We furthermore comment on the diagnostic and therapeutic options of this rare entity through our observation of the case and consideration of the 31 case reports published in the literature. PMID:27182171

  17. Prognostic significance of CD44 in human colon cancer and gastric cancer: Evidence from bioinformatic analyses

    PubMed Central

    Xia, Pu; Xu, Xiao-Yan

    2016-01-01

    CD44 is a well-recognized stem cell biomarker expressed in colon and gastric cancer. In order to identify whether CD44 mRNA could be used as a prognostic marker in colon and gastric cancer, bioinformatic analyses were used in this study. cBioPortal analysis and COSMIC analysis were used to explore the CD44 mutation. CD44 mRNA levels were evaluated by using SAGE Genie tools and Oncomine analysis. Kaplan-Meier Plotter was performed to identify the prognostic roles of CD44 mRNA in these two cancers. In this study, first, we found that low alteration frequency of CD44 mRNA in colon and gastric cancer. Second, the high CD44 mRNA level was found in colon and gastric cancer, and it correlated with a benign survival rate in gastric cancer. Third, CD4 and CD74 may be used as markers to predict the prognosis of colon and gastric cancer. However, the deep mechanism(s) of these results remains unclear, further studies have to be performed in the future. PMID:27323782

  18. Hyaluronate - Peanut Agglutinin Conjugates for Target-Specific Bioimaging of Colon Cancer.

    PubMed

    Beack, Songeun; Cho, Minsoo; Kim, Young-Eun; Ahn, G-One; Hahn, Sei Kwang

    2017-03-27

    Colon cancer is one of the most common death-related cancers in the world. For treating the colon cancer, it is crucial to detect and remove malignant lesions in the early time. Here, we developed hyaluronate (HA) - peanut agglutinin (PNA) conjugates for bioimaging of colon cancer. The HA-PNA conjugates were successfully synthesized by the coupling reaction between aldehyde modified HA and the N-terminal amine group of PNA. For diagnostic imaging, rhodamine B (RhoB) was chemically conjugated onto PNA in HA-PNA conjugates. After intraluminal injection of HA-PNA-RhoB conjugates into tumor-bearing mice, small-sized colon cancers could be effectively visualized by ex vivo IVIS imaging and two-photon microscopy. Taken together, we could confirm the feasibility of HA-PNA-RhoB conjugates as a bioimaging agent for detecting colon cancers. [Keywords] Hyaluronate; Peanut agglutinin; Colon cancer; Two-photon imaging; Diagnostics.

  19. Gastrointestinal microflora, food components and colon cancer prevention

    PubMed Central

    Davis, Cindy D.; Milner, John A.

    2009-01-01

    Evidence is emerging that the intestinal microbiota is intrinsically linked with overall health, including cancer risk. Moreover, its composition is not fixed, but can be influenced by several dietary components. Dietary modifiers, including the consumption of live bacteria (probiotics), nondigestible or limited digestible food constituents such as oligosaccharides (prebiotics) and polyphenols, or both (synbiotics), are recognized modifiers of the numbers and types of microbes and have been reported to reduce colon cancer risk experimentally. Microorganisms also have the ability to generate bioactive compounds from food components. Examples include equol from isoflavones, enterodiol and enterolactone from lignans, and urolithins from ellagic acid, which have also been demonstrated to retard experimentally induced cancers. The gastrointestinal microbiota can also influence both sides of the energy balance equation; namely, as a factor influencing energy utilization from the diet and as a factor that influences host genes that regulate energy expenditure and storage. Because of the link between obesity and cancer incidence and mortality, this complex relationship deserves greater attention. Thus, a complex interrelationship exists between the intestinal microbiota and colon cancer risk which can be modified by dietary components and eating behaviors. PMID:19716282

  20. Rectal prolapse as initial clinical manifestation of colon cancer.

    PubMed

    Chen, C-W; Hsiao, C-W; Wu, C-C; Jao, S-W

    2008-04-01

    Rectal prolapse as the initial clinical manifestation of colorectal cancer is uncommon. We describe the case of a 75-year-old woman who was diagnosed as having adenocarcinoma of the sigmoid colon after presenting with complete rectal prolapse. The tumor caused rectosigmoid intussusception and then it prolapsed out through the anus. She underwent rectosigmoidectomy and rectopexy. The postoperative course was uneventful. The relationship between colorectal cancer and rectal prolapse has not been clearly established. This case report describes an unusual presentation of colorectal cancer. It suggests that rectal prolapse can present as the initial symptom of colorectal cancer and may also be a presenting feature of the occult intra-abdominal pathology. The importance of adequate investigation such as colonoscopy should be emphasized in patients who develop a new onset of rectal prolapse.

  1. Spread of tumor microenvironment contributes to colonic obstruction through subperitoneal fibroblast activation in colon cancer

    PubMed Central

    Yokota, Mitsuru; Kojima, Motohiro; Higuchi, Youichi; Nishizawa, Yuji; Kobayashi, Akihiro; Ito, Masaaki; Saito, Norio; Ochiai, Atsushi

    2015-01-01

    We evaluated the influence of the cancer microenvironment formed by peritoneal invasion (CMPI) on clinical findings in colon cancer patients. In addition to the association with poor prognosis, we discovered a relationship with bowel obstruction. Detailed analysis revealed that clinical findings related to bowel obstruction occurred more frequently in patients with an elevated type tumor, which had peritoneal elastic laminal elevation to the tumor surface, compared to those with non-elevated type tumors among those with elastic laminal invasion (ELI). Lateral tumor spread and increase of tumor annularity rate in ELI-positive elevated type cases suggested the morphological progression from ELI-positive non-elevated type to elevated type. In addition, α-smooth muscle actin expression was the highest in ELI-positive elevated type, and prominent expressions were found not only in the deep tumor area but also in the shallow tumor area. Furthermore, contraction assays revealed the robust contractile ability of subperitoneal fibroblasts stimulated by cancer cell-conditioned medium. Our findings suggest that CMPI spread into the luminal side of the colonic wall along with tumor progression, which caused bowel obstruction through the activation of subperitoneal fibroblasts. However, although the clinical outcome was not different between the two types, the clinical findings were affected by the spread of CMPI. We are the first to explore how the alteration of the tumor-promoting microenvironment, along with tumor progression, contributes to the development of clinical findings. PMID:25613547

  2. Red meat and colon cancer: dietary haem, but not fat, has cytotoxic and hyperproliferative effects on rat colonic epithelium.

    PubMed

    Sesink, A L; Termont, D S; Kleibeuker, J H; Van Der Meer, R

    2000-10-01

    High intake of red meat is associated with an increased risk of colon cancer. It has been suggested that fat from red meat is responsible, because high fat intake increases the concentration of cytotoxic lipids in the colon. Experimental studies have not unequivocally supported such a role for fat, however. Recently, we showed that dietary haem, which is abundant in red meat, increased colonic cytotoxicity and epithelial proliferation. In this study, we wanted to clarify whether dietary fat affects colon cancer risk by itself or by modulating the detrimental effects of haem on the colonic epithelium. Rats were fed control or haem-supplemented diets with 10%, 25% or 40% of the energy derived from fat for 14 days. Faeces were collected for biochemical analyses. Colonic cytotoxicity was determined from the degree of lysis of erythrocytes by faecal water. Colonic epithelial proliferation was measured in vivo using [(3)H]thymidine incorporation. Increasing the fat content of the control diets stimulated faecal disposal of both fatty acids and bile acids. It also increased the concentration of fatty acids, but not that of bile acids, in faecal water in control rats. The cytolytic activity of faecal water and colonic epithelial proliferation were unaffected. Dietary haem increased faecal cation content and cytolytic activity of faecal water at all fat levels, suggesting that the colonic mucosa was exposed to high amounts of luminal irritants. This effect was smaller in rats on the low-fat diet. Dietary haem also increased colonic epithelial proliferation at all fat levels. The haem-induced effects were independent of fatty acids or bile acids in the faecal water. In western societies, 30-40% of ingested energy is supplied by dietary fat, so our results suggest that the association between consumption of red meat and risk of colon cancer is mainly due to its haem content, and is largely independent of dietary fat content.

  3. Body mass index and colon cancer screening: the road ahead.

    PubMed

    Tandon, Kanwarpreet; Imam, Mohamad; Ismail, Bahaa Eldeen Senousy; Castro, Fernando

    2015-02-07

    Screening for colorectal cancer (CRC) has been associated with a decreased incidence and mortality from CRC. However, patient adherence to screening is less than desirable and resources are limited even in developed countries. Better identification of individuals at a higher risk could result in improved screening efforts. Over the past few years, formulas have been developed to predict the likelihood of developing advanced colonic neoplasia in susceptible individuals but have yet to be utilized in mass screening practices. These models use a number of clinical factors that have been associated with colonic neoplasia including the body mass index (BMI). Advances in our understanding of the mechanisms by which obesity contributes to colonic neoplasia as well as clinical studies on this subject have proven the association between BMI and colonic neoplasia. However, there are still controversies on this subject as some studies have arrived at different conclusions on the influence of BMI by gender. Future studies should aim at resolving these discrepancies in order to improve the efficiency of screening strategies.

  4. Approaches that ascertain the role of dietary compounds in colonic cancer cells

    PubMed Central

    Bordonaro, Michael; Venema, Koen; Putri, Adeline K; Lazarova, Darina

    2014-01-01

    Preventive approaches against cancer have not been fully developed and applied. For example, the incidence of some types of cancer, including colon cancer, is highly dependent upon lifestyle, and therefore, amenable to prevention. Among the lifestyle factors, diet strongly affects the incidence of colon cancer; however, there are no definitive dietary recommendations that protect against this malignancy. The association between diet-derived bioactives and development of colonic neoplasms will remain ill defined if we do not take into account: (1) the identity of the metabolites present in the colonic lumen; (2) their concentrations in the colon; and (3) the effect of the colonic contents on the function of individual bioactives. We review two approaches that address these questions: the use of fecal water and in vitro models of the human colon. Compared to treatment with individual diet-derived compounds, the exposure of colon cancer cells to samples from fecal water or human colon simulators mimics closer the in vitro conditions and allows for more reliable studies on the effects of diet on colon cancer development. The rationale and the advantages of these strategies are discussed from the perspective of a specific question on how to analyze the combined effect of two types of bioactives, butyrate and polyphenol metabolites, on colon cancer cells. PMID:24578783

  5. Hyperspectral imaging fluorescence excitation scanning for colon cancer detection

    NASA Astrophysics Data System (ADS)

    Leavesley, Silas J.; Walters, Mikayla; Lopez, Carmen; Baker, Thomas; Favreau, Peter F.; Rich, Thomas C.; Rider, Paul F.; Boudreaux, Carole W.

    2016-10-01

    Optical spectroscopy and hyperspectral imaging have shown the potential to discriminate between cancerous and noncancerous tissue with high sensitivity and specificity. However, to date, these techniques have not been effectively translated to real-time endoscope platforms. Hyperspectral imaging of the fluorescence excitation spectrum represents new technology that may be well suited for endoscopic implementation. However, the feasibility of detecting differences between normal and cancerous mucosa using fluorescence excitation-scanning hyperspectral imaging has not been evaluated. The goal of this study was to evaluate the initial feasibility of using fluorescence excitation-scanning hyperspectral imaging for measuring changes in fluorescence excitation spectrum concurrent with colonic adenocarcinoma using a small pre-pilot-scale sample size. Ex vivo analysis was performed using resected pairs of colorectal adenocarcinoma and normal mucosa. Adenocarcinoma was confirmed by histologic evaluation of hematoxylin and eosin (H&E) permanent sections. Specimens were imaged using a custom hyperspectral imaging fluorescence excitation-scanning microscope system. Results demonstrated consistent spectral differences between normal and cancerous tissues over the fluorescence excitation range of 390 to 450 nm that could be the basis for wavelength-dependent detection of colorectal cancers. Hence, excitation-scanning hyperspectral imaging may offer an alternative approach for discriminating adenocarcinoma from surrounding normal colonic mucosa, but further studies will be required to evaluate the accuracy of this approach using a larger patient cohort.

  6. A recellularized human colon model identifies cancer driver genes

    PubMed Central

    Chen, Huanhuan Joyce; Wei, Zhubo; Sun, Jian; Bhattacharya, Asmita; Savage, David J; Serda, Rita; Mackeyev, Yuri; Curley, Steven A.; Bu, Pengcheng; Wang, Lihua; Chen, Shuibing; Cohen-Gould, Leona; Huang, Emina; Shen, Xiling; Lipkin, Steven M.; Copeland, Neal G.; Jenkins, Nancy A.; Shuler, Michael L.

    2016-01-01

    Refined cancer models are needed to bridge the gap between cell-line, animal and clinical research. Here we describe the engineering of an organotypic colon cancer model by recellularization of a native human matrix that contains cell-populated mucosa and an intact muscularis mucosa layer. This ex vivo system recapitulates the pathophysiological progression from APC-mutant neoplasia to submucosal invasive tumor. We used it to perform a Sleeping Beauty transposon mutagenesis screen to identify genes that cooperate with mutant APC in driving invasive neoplasia. 38 candidate invasion driver genes were identified, 17 of which have been previously implicated in colorectal cancer progression, including TCF7L2, TWIST2, MSH2, DCC and EPHB1/2. Six invasion driver genes that to our knowledge have not been previously described were validated in vitro using cell proliferation, migration and invasion assays, and ex vivo using recellularized human colon. These results demonstrate the utility of our organoid model for studying cancer biology. PMID:27398792

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

    PubMed

    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.

  8. Biological/Chemopreventive Activity of Stilbenes and Their Effect on Colon Cancer

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Colon cancer is one of the leading causes of cancer death in men and women in Western countries. Epidemiological studies have linked consumption of fruits and vegetables to a reduced risk of colon cancer, and small fruits are particularly rich sources of many active phytochemical stilbenes, such as ...

  9. Colon cancer: diagnosis and prognosis in the elderly.

    PubMed

    Block, G E

    1989-05-01

    Cancer of the colon and rectum appear to be epidemic in the US, with 150,000 cases expected during 1988. Two thirds of these patients are over age 60, and two thirds also have either full penetration of the bowel wall or metastases to regional lymph nodes. Mass screening via tests for occult blood in the stool is invaluable for detecting early carcinomas of the colon and rectum. Digital examination, endoscopy, and barium contrast radiographs help to confirm the diagnosis. Tumors of the colon and rectum are best treated operatively with appropriate lymphadenectomy and adequate margins, both proximally and distally, to guard against local recurrence. Certain factors, such as mucinous tumors, microinvasion, and non-exophytic tumors of the rectum have been shown to have a propensity for local recurrence. Local treatment by fulguration or electrocoagulation is advocated only for tiny tumors confined to a polyp, or for the extremely elderly or poor-risk patient. Radiation therapy appears to be an appropriate adjuvant to the treatment of rectal cancer either preoperatively or postoperatively.

  10. Robotic Surgery for Colon and Rectal Cancer.

    PubMed

    Park, Eun Jung; Baik, Seung Hyuk

    2016-01-01

    Robotic surgery, used generally for colorectal cancer, has the advantages of a three-dimensional surgical view, steadiness, and seven degrees of robotic arms. However, there are disadvantages, such as a decreased sense of touch, extra time needed to dock the robotic cart, and high cost. Robotic surgery is performed using various techniques, with or without laparoscopic surgery. Because the results of this approach are reported to be similar to or less favorable than those of laparoscopic surgery, the learning curve for robotic colorectal surgery remains controversial. However, according to short- and long-term oncologic outcomes, robotic colorectal surgery is feasible and safe compared with conventional surgery. Advanced technologies in robotic surgery have resulted in favorable intraoperative and perioperative clinical outcomes as well as functional outcomes. As the technical advances in robotic surgery improve surgical performance as well as outcomes, it increasingly is being regarded as a treatment option for colorectal surgery. However, a multicenter, randomized clinical trial is needed to validate this approach.

  11. The Role of Curcumin in Modulating Colonic Microbiota During Colitis and Colon Cancer Prevention

    PubMed Central

    McFadden, Rita-Marie T.; Larmonier, Claire B.; Shehab, Kareem W.; Midura-Kiela, Monica; Ramalingam, Rajalakshmy; Harrison, Christy A.; Besselsen, David G.; Chase, John H.; Caporaso, J. Gregory; Jobin, Christian; Ghishan, Fayez K.; Kiela, Pawel R.

    2015-01-01

    Background Intestinal microbiota influences the progression of colitis-associated colorectal cancer (CAC). With diet being a key determinant of the gut microbial ecology, dietary interventions are an attractive avenue for the prevention of CAC. Curcumin is the most active constituent of the ground rhizome of the Curcuma Longa plant, which has been demonstrated to have anti-inflammatory, anti-oxidative and anti-proliferative properties. Methods Il10−/− mice on 129/SvEv background were used as a model of CAC. Starting at 10 weeks of age, WT or Il10−/− mice received six weekly i.p. injections of azoxymethane (AOM) or saline, and were started on either a control or curcumin-supplemented diet. Stools were collected every 4 weeks for microbial community analysis. Mice were sacrificed at 30 weeks of age. Results Curcumin-supplemented diet increased survival, decreased colon weight/length ratio, and at 0.5%, entirely eliminated tumor burden. Although colonic histology indicated improvement with curcumin, no effects of mucosal immune responses have been observed in PBS/Il10−/− mice, and limited effects were seen in AOM/Il10−/− mice. In WT and in Il10−/− mice, curcumin increased bacterial richness, prevented age-related decrease in alpha diversity, increased the relative abundance of Lactobacillales, and decreased Coriobacterales order. Taxonomic profile of AOM/Il10−/− mice receiving curcumin was more similar to those of wild-type mice than those fed control diet. Conclusions In AOM/Il10−/− model, curcumin reduced or eliminated colonic tumor burden with limited effects on mucosal immune responses. The beneficial effect of curcumin on tumorigenesis was associated with the maintenance of a more diverse colonic microbial ecology. PMID:26218141

  12. The anatomy of the TNM for colon cancer

    PubMed Central

    Hueman, Matthew T.; Chen, Dechang; Patel, Jigar A.; Wang, Huan; Schwartz, Arnold M.

    2017-01-01

    Background To visualize the anatomy as revealed by dendrograms of the tumor, lymph node, and metastasis (TNM) staging system for colon cancer and compare it with the Dukes’ system. Methods A hierarchical clustering algorithm generated tree-structured dendrograms that stratified patients according to survival only. The dendrograms were constructed with the same prognostic variables used for the TNM. Because combinations of prognostic factors were stratified only on survival, additional factors of any number and type could be integrated into the TNM without changing the TNM categories. Results The algorithm provided a step-by-step visualization of the TNM and the Dukes’ system for colon cancer. Dendrograms and associated 5-year survival rates were generated for the T category only, the N category only, the T, N combination, and combinations of the T, N, and M, and the T, N, M with histological grade. Dendrograms revealed visual differences between the structure of TNM and the Dukes’ system of staging. Dendrograms also revealed how variations in prognostic factors changed survival. By cutting dendrograms along their dissimilarity axis, multiple prognostic subgroups could be created for colon cancer that may reflect outcomes that are more accurate to estimate. Conclusions Dendrograms provide a new way to view cancer patient staging. They reveal a visual step-by-step hierarchical relationship between survival rates and combinations of prognostic variables. The dendrograms also revealed fundamental differences between the TNM and the Dukes system of staging. By stratifying on survival only, additional factors including molecular factors can be added to the TNM, because it classifies patients according to survival rates only and not according to pre-set rules of prognostic factors and stage groups. The clinical implications of stratifying only survival are discussed. PMID:28280604

  13. The content of hope in ambulatory patients with colon cancer.

    PubMed

    Beckman, Emily S; Helft, Paul R; Torke, Alexia M

    2013-01-01

    Although hope is a pervasive concept in cancer treatment, we know little about how ambulatory patients with cancer define or experience hope. We explored hope through semistructured interviews with ten patients with advanced (some curable, some incurable) colon cancer at one Midwestern, university-based cancer center. We conducted a thematic analysis to identify key concepts related to patient perceptions of hope. Although we did ask specifically about hope, patients also often revealed their hopes in response to indirect questions or by telling stories about their cancer experience. We identified four major themes related to hope: 1) hope is essential, 2) a change in perspective, 3) the content of hope, and 4) communicating about hope. The third theme, the content of hope, included three subthemes: a) the desire for normalcy, b) future plans, and c) hope for a cure. We conclude that hope is an essential concept for patients undergoing treatment for cancer as it pertains to their psychological well-being and quality of life, and hope for a cure is not and should not be the only consideration. In a clinical context, the exploration of patients' hopes and aspirations in light of their cancer diagnosis is important because it provides a frame for understanding their goals for treatment. Exploration of the content of patients' hope can not only help to illuminate misunderstandings but also clarify how potential treatments may or may not contribute to achieving patients' goals.

  14. An Apta-Biosensor for Colon Cancer Diagnostics

    PubMed Central

    Ahmadzadeh Raji, Mojgan; Amoabediny, Ghasem; Tajik, Parviz; Hosseini, Morteza; Ghafar-Zadeh, Ebrahim

    2015-01-01

    This paper reports the design and implementation of an aptasensor using a modified KCHA10a aptamer. This aptasensor consists of a functionalized electrodes using various materials including 11-mercaptoandecanoic acid (11-MUA) and modified KCHA10a aptamer. The HCT 116, HT 29 and HEp-2 cell lines are used in this study to demonstrate the functionality of aptasensor for colon cancer detection purposes. Flow cytometry, fluorescence microscopy and electrochemical cyclic voltammetry are used to verify the binding between the target cells and aptamer. The limit of detection (LOD) of this aptasensor is equal to seven cancer cells. Based on the experimental results, the proposed sensor can be employed for point-of-care cancer disease diagnostics. PMID:26404293

  15. [A case of early gastric cancer completely responding to adjuvant chemotherapy for advanced colon cancer].

    PubMed

    Tanaka, Ryo; Kameyama, Hitoshi; Nakano, Mae; Ichikawa, Hiroshi; Hanyu, Takaaki; Nakano, Masato; Ishikawa, Takashi; Shimada, Yoshifumi; Sakata, Jun; Kobayashi, Takashi; Kosugi, Shinichi; Minagawa, Masahiro; Koyama, Yu; Wakai, Toshifumi

    2014-11-01

    A 70-year-old man was referred to our hospital with ascending colon cancer (cT3N1M0, Stage IIIa), which was found during examinations following a positive fecal occult blood test. The patient was also diagnosed with early gastric cancer (cT1a, N0, M0, Stage IA)during a preoperative gastroscopy examination. A laparoscopically assisted right colectomy and D3 lymphadenectomy was performed for the ascending colon cancer. The postoperative pathological diagnosis was Stage IIIb (pT3N2), he was administered in combination with capecitabine plus oxaliplatin (CapeOX) as adjuvant chemotherapy before the treatment for the colon cancer. After 6 months of adjuvant chemotherapy, we were unable to detect any gastric lesions at the same location using gastroscopy, and so diagnosed a clinical complete response. A follow-up gastroscopy 6 months later showed the same findings. The patient has had no recurrence of gastric cancer for 18 months after the initial operation. He will continue to be followed up closely using gastroscopy. In this case, CapeOX as adjuvant chemotherapy for advanced colon cancer was also effective for early gastric cancer.

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

    PubMed Central

    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

    Background 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. Aim To gain insight into the influence of a diabetic environment on colon cancer characteristics and outcomes. Material and methods 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. Results 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. Conclusion Our findings point towards a mild or negligible effect of the diabetes environment on colon cancer behavior, once cancer has already developed. PMID:28253286

  17. Anthocyanin-containing purple-fleshed potatoes suppress colon tumorigenesis via elimination of colon cancer stem cells.

    PubMed

    Charepalli, Venkata; Reddivari, Lavanya; Radhakrishnan, Sridhar; Vadde, Ramakrishna; Agarwal, Rajesh; Vanamala, Jairam K P

    2015-12-01

    Cancer stem cells (CSCs) are shown to be responsible for initiation and progression of tumors in a variety of cancers. We previously showed that anthocyanin-containing baked purple-fleshed potato (PP) extracts (PA) suppressed early and advanced human colon cancer cell proliferation and induced apoptosis, but their effect on colon CSCs is not known. Considering the evidence of bioactive compounds, such as anthocyanins, against cancers, there is a critical need to study anticancer activity of PP, a global food crop, against colon CSCs. Thus, isolated colon CSCs (positive for CD44, CD133 and ALDH1b1 markers) with functioning p53 and shRNA-attenuated p53 were treated with PA at 5.0 μg/ml. Effects of baked PP (20% wt/wt) against colon CSCs were also tested in vivo in mice with azoxymethane-induced colon tumorigenesis. Effects of PA/PP were compared to positive control sulindac. In vitro, PA suppressed proliferation and elevated apoptosis in a p53-independent manner in colon CSCs. PA, but not sulindac, suppressed levels of Wnt pathway effector β-catenin (a critical regulator of CSC proliferation) and its downstream proteins (c-Myc and cyclin D1) and elevated Bax and cytochrome c, proteins-mediating mitochondrial apoptosis. In vivo, PP reduced the number of crypts containing cells with nuclear β-catenin (an indicator of colon CSCs) via induction of apoptosis and suppressed tumor incidence similar to that of sulindac. Combined, our data suggest that PP may contribute to reduced colon CSCs number and tumor incidence in vivo via suppression of Wnt/β-catenin signaling and elevation of mitochondria-mediated apoptosis.

  18. Radioimmunotoxin Therapy of Experimental Colon and Ovarian Cancer

    SciTech Connect

    Buchsbaum, Donald J.; Vallera, Daniel A.

    2006-02-09

    To pursue the development of radiolabeled immunotoxins (RIT) for colon cancer, it was first necessary to identify an immunotoxin (IT) that could selectively kill colon cancer cell lines. Recently, our collaborators in the Vallera laboratory have observed that potent recombinant IT can be synthesized using recombinant single chain antibodies (sFv) spliced to truncated diphtheria toxin (DT) consisting of the first 390 amino acids of native DT. DT was chosen as a toxin because it is a catalytic bacterial toxin that is easily manipulated in genetic engineering studies. Also, the Vallera lab has developed new procedures for preparing the sFv fusion toxins from bacterial inclusion bodies such as DT and another good genetic engineering toxin pseudomonas exotoxin (PE) based on detergent refolding. This allows for enhanced yields and higher purity that is essential for generating the protein that will be needed for preparation of larger amounts of RIT for therapy. Many potential sFvs were considered for targeting colon cancer. The best results have been obtained with an sFv recognizing EpCam. EpCam, also known as ESA or EGP40, is a 40 kDa epithelial transmembrane glycoprotein found on the basolateral surface of simple, pseudostratified, and transitional epithelia. It has been found overexpressed on 81% of adenocarcinomas of the colon (Went et al. Human pathology 35:122, 2004). EpCam sliced to DT (DTEpCam) was highly potent in studies in which we measured its ability to inhibit the proliferation of the HT-29 and COLO 205 colon cancer cell lines since we measured its IC50 at 1-2 x 10-2 nM. Potency is important, but is also critical that DTEpCam is selective in its cytotoxicity against EpCam-expressing target colon cancer cells. The activity of DTEpCam was highly selective since irrelevant control IT that did not recognize any markers on cancer cells, did not show any activity against the same colon cancer cell lines. Also, blocking studies were performed in which DTEpCam was

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

    PubMed Central

    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

  20. Evaluation of a breast and colon cancer survivorship program.

    PubMed

    McCollum, Kennon H; Wood, Felecia G; Auriemma, Kimberly

    2014-04-01

    This article describes a cancer survivorship program that addressed quality of life (QOL) changes related to chemotherapy. The program focused on adult breast and colon cancer survivors at a community oncology practice in the southeastern United States, and consisted of an educational visit designed to identify and address QOL changes that occurred as a result of chemotherapy. The QOL of Cancer Survivors (QOL-CS) survey administered before and after the visit analyzed QOL metrics, which were combined with program evaluation data to assess physical, psychosocial, social, and spiritual well-being changes that may have occurred as a result of program participation. Differences in QOL-CS scores did not represent statistically significant changes in QOL for program participants. However, program evaluation responses identified perceived changes in QOL as a result of participating in cancer treatment and a subsequent cancer survivorship program, which demonstrated clinical significance for program participants. Physical, psychosocial, social, and spiritual well-being measures were affected by program participation. Improvement in distress related to the initial cancer diagnosis and family distress were the most significant reported changes, and male gender and advanced age were associated with improved psychosocial well-being.

  1. Dealing with colon cancer: one woman's emotional journey.

    PubMed

    Wilson, Candice T; Fletcher, Paula C

    2002-11-01

    Although death is inevitable, it continues to remain a taboo issue for society. A failure to discuss the unavoidable may represent a safeguard to avoid dealing with mortality and related fears. Many patients who are terminally ill spend their days feeling alone, misunderstood, and afraid. Kubler-Ross attempted to strip death of its negative connotations and to provide a venue for the terminally ill to have a voice. Using information from more than 200 clinical interviews, Kubler-Ross revealed a trend in emotions over time in most, but not all, of her patients, which enabled her to formulate a model of coping with death that included 5 interdependent emotional stages: denial, anger, bargaining, depression, and acceptance. This model has become the most widely accepted and popularized model on death and dying, often cited as the Five Stages of Grief." However, given the lack of research concerning Kubler-Ross's model, completing work in this area seems warranted. The purpose of this case study was to examine one individual's emotional journey after being diagnosed with terminal colon cancer. More specifically, the goals were twofold: (1) to provide the participant with a voice and to allow her story to be told by examining the major external events (ie,surgery, chemotherapy) occurring since the diagnosis that affected her emotional and physical well-being and (2) to determine whether the participant's emotional journey paralleled Kubler-Ross's model, to what extent, and whether new emotions or stages occurred. The participant, a 50-year-old female, was diagnosed with stage 4 Duke Stage D colon cancer. Qualitative information was collected in face-to-face interviews, newspaper articles about the participant, and e-mail correspondence (as form letters to a group of friends and supporters) and subsequently analyzed for trends. The overall results revealed clear existence of the 5 stages of grief as outlined in the Kubler-Ross model. Analyses also revealed that the

  2. Molecular mechanisms linking adipokines to obesity-related colon cancer: focus on leptin.

    PubMed

    Drew, Janice E

    2012-02-01

    Obesity is linked to increased risk of colon cancer, currently the third most common cancer. Consequently rising levels of obesity worldwide are likely to significantly impact on obesity-related colon cancers in the decades to come. Understanding the molecular mechanisms whereby obesity increases colon cancer risk is thus a focus for research to inform strategies to prevent the increasing trend in obesity-related cancers. This review will consider research on deregulation of adipokine signalling, a consequence of altered adipokine hormone secretion from excess adipose tissue, with a focus on leptin, which has been studied extensively as a potential mediator of obesity-related colon cancer. Numerous investigations using colon cell lines in vitro, in vivo studies in rodents and investigations of colon cancer patients illuminate the complexity of the interactions of leptin with colon tissues via leptin receptors expressed by the colon epithelium. Although evidence indicates a role for leptin in proliferation of colon epithelial cells in vitro, this has been contradicted by studies in rodent models. However, recent studies have indicated that leptin may influence inflammatory mediators linked with colon cancer and also promote cell growth dependent on genotype and is implicated in growth promotion of colon cancer cells. Studies in human cancer patients indicate that there may be different tumour sub-types with varying levels of leptin receptor expression, indicating the potential for leptin to induce variable responses in the different tumour types. These studies have provided insights into the complex interplay of adipokines with responsive tissues prone to obesity-related colon cancer. Deregulation of adipokine signalling via adipokine receptors located in the colon appears to be a significant factor in obesity-related colon cancer. Molecular profiling of colon tumours will be a useful tool in future strategies to characterise the influence that adipokines may have

  3. Crosstalk between Wnt/β-catenin and Hedgehog/Gli signaling pathways in colon cancer and implications for therapy.

    PubMed

    Song, Li; Li, Zhuo-Yu; Liu, Wei-Ping; Zhao, Mei-Rong

    2015-01-01

    Wnt/β-catenin and Hedgehog/Gli signalings play key roles in multiple biogenesis such as embryonic development and tissue homeostasis. Dysregulations of these 2 pathways are frequently found in most cancers, particularly in colon cancer. Their crosstalk has been increasingly appreciated as an important mechanism in regulating colon cancer progression. Our studies into the link between Wnt/β-catenin and Hedgehog/Gli signalings in colon cancer revealed several possible crosstalk points and suggested potential therapeutic strategies for colon cancer.

  4. The Incidence Characteristics of Second Primary Malignancy after Diagnosis of Primary Colon and Rectal Cancer: A Population Based Study

    PubMed Central

    Guan, Xu; Jin, Yinghu; Chen, Yinggang; Jiang, Zheng; Liu, Zheng; Zhao, Zhixun; Yan, Peng; Wang, Guiyu; Wang, Xishan

    2015-01-01

    Background With the expanding population of colorectal cancer (CRC) survivors in the United States, one concerning issue is the risk of developing second primary malignancies (SPMs) for these CRC survivors. The present study attempts to identify the incidence characteristics of SPMs after diagnosis of first primary colon cancer (CC) and rectal cancer (RC). Methods 189,890 CC and 83,802 RC cases were identified from Surveillance, Epidemiology and End Results Program (SEER) database. We performed rate analysis on incidence trend of SPMs in both CC and RC. Expected incidence rates were stratified by age, race and stage, calendar year of first CRC diagnosis and latency period since first CRC diagnosis. The standardized incidence ratios (SIRs), measure for estimating risk of SPMs, were calculated for CC and RC respectively. Results The trends of incidence of SPMs in both CC and RC were decreasing from 1992 to 2012. Both CC and RC survivors had higher risk of developing SPMs (SIRCC = 1.13; SIRRC = 1.05). For CC patients, the highest risks of SPM were cancers of small intestine (SIR = 4.03), colon (SIR = 1.87) and rectum (SIR = 1.80). For RC patients, the highest risks of SPMs were cancers of rectum (SIR = 2.88), small intestine (SIR = 2.16) and thyroid (SIR = 1.46). According to stratified analyses, we also identified incidence characteristics which were contributed to higher risk of developing SPMs, including the age between 20 and 40, American Indian/Alaska Native, localized stage, diagnosed at calendar year from 2002 to 2012 and the latency between 12 and 59 months. Conclusions Both CC and RC survivors remain at higher risk of developing SPMs. The identification of incidence characteristics of SPMs is extremely essential for continuous cancer surveillance among CRC survivors. PMID:26571301

  5. Pectin matrix as oral drug delivery vehicle for colon cancer treatment.

    PubMed

    Wong, Tin Wui; Colombo, Gaia; Sonvico, Fabio

    2011-03-01

    Colon cancer is the fourth most common cancer globally with 639,000 deaths reported annually. Typical chemotherapy is provided by injection route to reduce tumor growth and metastasis. Recent research investigates the oral delivery profiles of chemotherapeutic agents. In comparison to injection, oral administration of drugs in the form of a colon-specific delivery system is expected to increase drug bioavailability at target site, reduce drug dose and systemic adverse effects. Pectin is suitable for use as colon-specific drug delivery vehicle as it is selectively digested by colonic microflora to release drug with minimal degradation in upper gastrointestinal tract. The present review examines the physicochemical attributes of formulation needed to retard drug release of pectin matrix prior to its arrival at colon, and evaluate the therapeutic value of pectin matrix in association with colon cancer. The review suggests that multi-particulate calcium pectinate matrix is an ideal carrier to orally deliver drugs for site-specific treatment of colon cancer as (1) crosslinking of pectin by calcium ions in a matrix negates drug release in upper gastrointestinal tract, (2) multi-particulate carrier has a slower transit and a higher contact time for drug action in colon than single-unit dosage form, and (3) both pectin and calcium have an indication to reduce the severity of colon cancer from the implication of diet and molecular biology studies. Pectin matrix demonstrates dual advantages as drug carrier and therapeutic for use in treatment of colon cancer.

  6. Oral 5-fluorouracil colon-specific delivery through in vivo pellet coating for colon cancer and aberrant crypt foci treatment.

    PubMed

    Bose, A; Elyagoby, A; Wong, T W

    2014-07-01

    In situ coating of 5-fluorouracil pellets by ethylcellulose and pectin powder mixture (8:3 weight ratio) in capsule at simulated gastrointestinal media provides colon-specific drug release in vitro. This study probes into pharmacodynamic and pharmacokinetic profiles of intra-capsular pellets coated in vivo in rats with reference to their site-specific drug release outcomes. The pellets were prepared by extrusion-spheronization technique. In vitro drug content, drug release, in vivo pharmacokinetics, local colonic drug content, tumor, aberrant crypt foci, systemic hematology and clinical chemistry profiles of coated and uncoated pellets were examined against unprocessed drug. In vivo pellet coating led to reduced drug bioavailability and enhanced drug accumulation at colon (179.13 μg 5-FU/g rat colon content vs 4.66 μg/g of conventional in vitro film-coated pellets at 15 mg/kg dose). The in vivo coated pellets reduced tumor number and size, through reforming tubular epithelium with basement membrane and restricting expression of cancer from adenoma to adenocarcinoma. Unlike uncoated pellets and unprocessed drug, the coated pellets eliminated aberrant crypt foci which represented a putative preneoplastic lesion in colon cancer. They did not inflict additional systemic toxicity. In vivo pellet coating to orally target 5-fluorouracil delivery at cancerous colon is a feasible therapeutic treatment approach.

  7. Role of periostin in esophageal, gastric and colon cancer

    PubMed Central

    Moniuszko, Tadeusz; Wincewicz, Andrzej; Koda, Mariusz; Domysławska, Izabela; Sulkowski, Stanisław

    2016-01-01

    Periostin, also known as osteoblast-specific factor 2, is a cell-adhesion protein with pleiotropic properties. The protein serves a vital role in the maintenance and development of tooth and bone tissue, in addition to cardiac development and healing. Periostin levels are increased in several forms of cancer, including pancreatic, ovarian, colon, lung, breast, gastric, thyroid, and esophageal head and neck carcinomas. The present review highlights the key role of periostin in tumorigenesis, particularly in increasing cell survival, invasion, angiogenesis, epithelial-mesenchymal transition and metastasis of carcinoma cells by interacting with numerous cell-surface receptors, including integrins, in the phosphoinositide 3-kinase-Akt pathway. In addition, periostin actively affects the canonical Wnt signaling pathway of colorectal tumorigenesis. The current review focused on the involvement of periostin in the development of colorectal, esophageal and gastric cancer. PMID:27446351

  8. Proteogenomic characterization of human colon and rectal cancer

    SciTech Connect

    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.

  9. Differences in carcinoembryonic antigen levels between colon and rectal cancer.

    PubMed

    Ding, Yunlong; Xuan, Weibo; Chen, Chunlin; Chen, Zhe; Yang, Ziyi; Zuo, Yunfei; Ren, Shuangyi

    2014-07-01

    The aim of the present study was to investigate the levels of the serum tumor biomarker carcinoembryonic antigen (CEA) in patients with carcinoma of the colon and rectum in different clinical stages. Colorectal cancer (CRC) is one of the most commonly diagnosed types of cancer worldwide and previous studies have reported rapidly updated therapeutic regimes. While the majority of studies focus on CRC as a single entity, certain studies distinguish colon cancer (CC) from rectal cancer (RC), as there is a hypothesis stating that CC and RC are two naturally different entities. CEA is reported to be an important tumor-associated antigen overexpressed in CRC, which is routinely detected as a significant indicator of CRC. Our study aimed to identify potential differences in the expression of CEA between CC and RC, which may, to some degree, reflect the natural differences between the two. We investigated 240 CRC cases between July, 2010 and December, 2012 from The First and Second Affiliated Hospitals of Dalian Medical University, including 117 CC and 123 RC patients with tumors classified by Duke's staging as A-D. The serum CEA level was measured preoperatively by radioimmunoassays as a routinely used auxiliary indicator. The expression of CEA differed between CC and RC, with the former exhibiting variation among the four stages, whereas no variation was observed in RC. In addition, there were differences between CC and RC regarding the CEA level in stage C and D. Furthermore, the CEA level in stage C of CC was significantly lower compared to that in any other stage. In conclusion, the intrinsic distribution of the CEA level between CC and RC suggests that CC and RC may be two naturally different entities; the significantly low CEA level in stage C of CC indicates that stage C may be crucial in the evolution of CC.

  10. [A case of cerebellum metastasis from colon cancer].

    PubMed

    Tanaka, Akiyoshi; Honma, Kiichi; Kondo, Hiroshi

    2009-11-01

    We report a case of cerebellum metastasis from transverse colon cancer, which had no evidence of recurrence in the thoracoabdominal region by chemotherapy and resection of liver and lung metastases after initial operation. The case is a 71-year-old male. We performed a radical resection of transverse colon cancer (D2) in 2001. The finding was moderately-differentiated adenocarcinoma, se, n1, ly1, v2, H0, P0, M0, stage IIIa. Relapsing tumor, which metastasized to the liver in 3 years, the right lung in 4 years and 8 months and the left lung in 5 years and 11 months after initial operation, were totally resected. Following the partial resection of the left lung, he received a treatment with 12 times of mFOLFOX6 and S-1+PSK. There was a good control observed in the thoracoabdominal region with no metastases for 14 months. However, drift and dizziness developed in April 2008, and cerebellum metastasis was diagnosed by MRI. He underwent a partial resection of cerebellum tumor, radiation therapy and FOLFIRI. He has been alive for 1 year after the treatment of the cerebellum metastasis, and there has been no evidence of recurrence in the thoracoabdominal region in 8 years after initial operation.

  11. Colon cancer prediction with genetic profiles using intelligent techniques.

    PubMed

    Alladi, Subha Mahadevi; P, Shinde Santosh; Ravi, Vadlamani; Murthy, Upadhyayula Suryanarayana

    2008-01-01

    Micro array data provides information of expression levels of thousands of genes in a cell in a single experiment. Numerous efforts have been made to use gene expression profiles to improve precision of tumor classification. In our present study we have used the benchmark colon cancer data set for analysis. Feature selection is done using t-statistic. Comparative study of class prediction accuracy of 3 different classifiers viz., support vector machine (SVM), neural nets and logistic regression was performed using the top 10 genes ranked by the t-statistic. SVM turned out to be the best classifier for this dataset based on area under the receiver operating characteristic curve (AUC) and total accuracy. Logistic Regression ranks as the next best classifier followed by Multi Layer Perceptron (MLP). The top 10 genes selected by us for classification are all well documented for their variable expression in colon cancer. We conclude that SVM together with t-statistic based feature selection is an efficient and viable alternative to popular techniques.

  12. Consumption of lycopene inhibits the growth and progression of colon cancer in a mouse xenograft model

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A previous study indicated that lycopene could significantly inhibit the proliferation of human colon cancer cells in vitro. However, the in vivo anticancer effects of lycopene against colon cancer have not been demonstrated yet. Therefore, this study investigated whether consumption of lycopene cou...

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

    PubMed

    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.

  14. [A new immuno-PCR format for serological diagnosis of colon cancer].

    PubMed

    Nikitina, I G; Sabirova, E Iu; Solopova, O N; Surzhikov, S A; Grineva, E N; Karpov, V L; Lisitsyn, N A; Beresten', S F

    2014-01-01

    Anew immuno-PCR format is described that is based on detection of membrane protein CDH17 in serum exosomes. Format application allows distinction between sera samples of healthy donors and colon cancer patients. Obtained results open a possibility of serological colon cancer diagnosis in high risk groups.

  15. Study shows colon and rectal tumors constitute a single type of cancer

    Cancer.gov

    The pattern of genomic alterations in colon and rectal tissues is the same regardless of anatomic location or origin within the colon or the rectum, leading researchers to conclude that these two cancer types can be grouped as one, according to The Cancer

  16. Association between TLR-9 polymorphisms and colon cancer susceptibility in Saudi Arabian female patients

    PubMed Central

    Semlali, Abdelhabib; Parine, Narasimha Reddy; Al Amri, Abdullah; Azzi, Arezki; Arafah, Maha; Kohailan, Muhammad; Shaik, Jilani P; Almadi, Majid Abdulrahman; Aljebreen, Abdulrahman M; Alharbi, Othman; Ali Azzam, Nahla; Rouabhia, Mahmoud; Alanazi, Mohammad Saud

    2017-01-01

    Objective The authors aimed to explore the relationship between the expression/polymorphisms of TLR-9 and susceptibility to colon cancer development in the Saudi Arabian population. Methods In total, blood samples from 115 patients with colon cancer and 102 participants without colon cancer were analyzed in this study. Three single-nucleotide polymorphisms (SNPs) were selected from the TLR-9 gene, including two sites within the TLR-9 gene’s promoter region (rs352144 and rs187084) and one site in a TLR-9 intron region (rs5743839). Odds ratios (ORs) and 95% confidence intervals (CIs) were computed from logistic regression models after adjusting for age, gender, and tumor localization. To investigate the differential expression of TLR-9 in colon cancer, TLR-9 expression was evaluated using quantitative real-time reverse transcription polymerase chain reaction on 40 matched normal and colon tissues. Results The authors found that TLR-9 expression was decreased in colon cancer tissues as compared with that in normal tissues. Moreover, significant associations between the TLR-9 rs187084 SNP and colon cancer risk were observed in female patients only. In rs187084, the T allele had a significantly lower frequency (2.8 times) in female cancer patients than in controls (0.27 vs 0.41). The TLR-9 rs352139 and rs352144 SNPs were significantly associated with colon cancer development when the tumor was located in the rectal area. Conclusion The findings support the hypothesis that TLR-9 has an anticancer role in colon cancer development. Furthermore, genetic variation may influence colon cancer development, and SNPs in TLR-9 could serve as biomarkers for decision making in the treatment of females with rectal cancer. PMID:28031717

  17. Prophylactic vaccine approach for colon and pancreatic cancers: present and future.

    PubMed

    Janakiram, N B; Mohammed, A; Bronze, M S; Rao, C V

    2012-01-01

    Vaccines against cancers have not been as effective as vaccines against infectious diseases. However, recent studies have advanced our understanding of the stages of tumor cell development and of mechanisms of immune surveillance, immune suppression, and of tumor escape from the immune system. The development of animal models that mimic development of human cancers has helped advance the understanding of these processes and is aiding the development of greatly improved vaccines. Here we review the recent progress in developing vaccines and prophylactic approaches for pancreatic and colon cancers. Improved understanding of the expression of various oncogenes and tumor-associated antigens helps in selecting antigenic targets for stage-specific immune prevention. Identification of the earliest alterations in precancerous lesions and selection of epitopes unique to the aberrant cells and capable of triggering strong cytotoxic and helper T cell responses may aid the development of safe and effective vaccines for use in those at high risk of progressing to invasive cancers. The responses can be enhanced with carefully selected adjuvants to boost immunity and by selecting epitopes that are expressed on dendritic cells, thereby promoting T cell responses. Tumor resistance via loss of the targeted antigen can be mitigated by inclusion of multiple tumor epitopes in vaccine constructs. Tumor immune escape can be diminished by targeting various immunosuppressive mechanisms used by different tumors, such as tumor production of immunosuppressive cytokines (e.g., interleukin 10, and Transforming Growth Factor-beta, which can promote activity of immunosuppressive regulatory T cells), or by inhibiting production of inflammatory prostanoids with combined cyclooxygenase/lipoxygenase inhibitors. Finally, prevention of many cancers may be enhanced by carefully selecting and scheduling of vaccine administration in combination with other chemotherapeutic or chemopreventive agents

  18. Preoperative serum markers for individual patient prognosis in stage I-III colon cancer.

    PubMed

    Giessen-Jung, Clemens; Nagel, Dorothea; Glas, Maria; Spelsberg, Fritz; Lau-Werner, Ulla; Modest, Dominik Paul; Schulz, Christoph; Heinemann, Volker; Di Gioia, Dorit; Stieber, Petra

    2015-09-01

    Carcinoembryonic antigen (CEA) remains the only recommended biomarker for follow-up care of colorectal cancer (CRC), but besides CEA, several other serological parameters have been proposed as prognostic markers for CRC. The present retrospective analysis investigates a comprehensive set of serum markers with regard to cancer-specific survival (CSS) and disease-free survival (DFS). A total of 472 patients with colon cancer underwent surgery for curative intent between January 1988 and June 2007. Preoperative serum was analyzed for the following parameters: albumin, alkaline phosphatase (aP), beta-human chorionic gonadotropin (βhCG), bilirubin, cancer antigen 125 (CA 125), cancer antigen 19-9 (CA 19-9), CA 72-4, CEA, C-reactive protein (CRP), cytokeratin-19 soluble fragment (CYFRA 21-1), ferritin, gamma-glutamyltransferase (γGT), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), hemoglobin, haptoglobin, interleukin-6, interleukin-8, creatinine, lactate dehydrogenase (LDH), serum amyloid A (SAA), and 25-hydroxyvitamin D. After a median follow-up period of 5.9 years, the overall 3- and 5-year CSS was 91.7 and 84.9 % and DFS rates were 82.7 % (3 years) and 77.6 % (5 years). Multivariate analyses confirmed preoperative CEA as an independent prognostic factor with regard to CSS and DFS. CA 19-9 and γGT also provided prognostic value for CSS and DFS, respectively. Younger age was negatively associated with DFS. According to UICC stage, CEA provided significant prognostic value with regard to CSS and DFS, while CA 19-9 was only prognostic for CSS. Combined analysis is able to identify patients with favorable prognosis. In addition to tumor baseline parameters, preoperative CEA could be confirmed as prognostic marker in colon cancer. CA 19-9 and γGT also provide additional prognostic value with regard to survival and recurrence in stage III and stage I disease, respectively. The combined use of CEA together with CA 19-9 and γGT improve

  19. Methylselenol, a selenium metabolite, inhibits colon cancer cell growth and cancer xenografts in C57BL/6 mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Data indicate that methylselenol is a critical selenium (Se) metabolite for anticancer activity in vivo but its role in colon cancer prevention remains to be characterized. This study tested the hypothesis that methylselenol inhibits the growth of colon cancer cells and tumors. We found that submicr...

  20. Classification of Colon Cancer Patients Based on the Methylation Patterns of Promoters

    PubMed Central

    Choi, Wonyoung; Lee, Jungwoo; Lee, Jin-Young; Lee, Sun-Min; Kim, Da-Won

    2016-01-01

    Diverse somatic mutations have been reported to serve as cancer drivers. Recently, it has also been reported that epigenetic regulation is closely related to cancer development. However, the effect of epigenetic changes on cancer is still elusive. In this study, we analyzed DNA methylation data on colon cancer taken from The Caner Genome Atlas. We found that several promoters were significantly hypermethylated in colon cancer patients. Through clustering analysis of differentially methylated DNA regions, we were able to define subgroups of patients and observed clinical features associated with each subgroup. In addition, we analyzed the functional ontology of aberrantly methylated genes and identified the G-protein-coupled receptor signaling pathway as one of the major pathways affected epigenetically. In conclusion, our analysis shows the possibility of characterizing the clinical features of colon cancer subgroups based on DNA methylation patterns and provides lists of important genes and pathways possibly involved in colon cancer development. PMID:27445647

  1. [Active surveillance in prostate cancer and quality of life].

    PubMed

    Dominguez Escrig, Jose L; Romero, Rocio

    2014-06-01

    Active surveillance was born as a therapeutic strategy for a well selected group of patients with low risk prostate cancer with the aim to defer or completely avoid the negative impact of secondary effects of curative therapies. Nevertheless, the patient who chooses this treatment does it at the expense of greater anxiety and doubts about the possible progression of the disease. The main psychological features influencing the quality of life of these patients are, on one hand anxiety, due to the uncertainty and fear to disease progression, and on the other hand, the difficult decision making process. Among the factors that seem to influence the election are: urologist's recommendation, effects on urinary function, age and impact of the therapy on sexual function. In the timorous journey walked, it is recommended to apply psycho-educational programs, with the objective of increasing the perceived control and adaptive confrontation. We propose an intervention with 4 group sessions, the objectives of which would be first to improve the decision making process and diminish the fear to progression and, second to reinforce the information already given at the time of diagnosis and increase the sensation of control, e.g promoting healthy habits.

  2. Down-regulation of GPR137 expression inhibits proliferation of colon cancer cells.

    PubMed

    Zhang, Kai; Shen, Zhen; Liang, Xianjun; Liu, Tongjun; Wang, Tiejun; Jiang, Yang

    2014-11-01

    G protein-coupled receptors (GPRs) are highly related to oncogenesis and cancer metastasis. G protein-coupled receptor 137 (GPR137) was initially reported as a novel orphan GPR about 10 years ago. Some orphan GPRs have been implicated in human cancers. The aim of this study is to investigate the role of GPR137 in human colon cancer. Expression levels of GRP137 were analyzed in different colon cancer cell lines by quantitative polymerase chain reaction and western blot analysis. Lentivirus-mediated short hairpin RNA was specifically designed to knock down GPR137 expression in colon cancer cells. Cell viability was measured by methylthiazoletetrazolium and colony formation assays. In addition, cell cycle characteristic was investigated by flow cytometry. GRP137 expression was observed in all seven colon cancer cell lines at different levels. The mRNA and protein levels of GPR137 were down-regulated in both HCT116 and RKO cells after lentivirus infection. Lentivirus-mediated silencing of GPR137 reduced the proliferation rate and colonies numbers. Knockdown of GPR137 in both cell lines led to cell cycle arrest in the G0/G1 phase. These results indicated that GPR137 plays an important role in colon cancer cell proliferation. A better understanding of GPR137's effects on signal transduction pathways in colon cancer cells may provide insights into the novel gene therapy of colon cancer.

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

    PubMed Central

    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. PMID:28045428

  4. A sociobehavioural perspective on genetic testing and counselling for heritable breast, ovarian and colon cancer.

    PubMed Central

    Macdonald, K G; Doan, B; Kelner, M; Taylor, K M

    1996-01-01

    Testing for susceptibility to heritable breast, ovarian and colon cancer has unique psychosocial costs. Negative test results may not be sufficient to relieve anxiety, and positive results can cause sufficient distress to compromise patient compliance with surveillance and risk reduction measures. More needs to be learned about how sociocultural factors affect the understanding of risk, how decisions to undergo testing are made and how information about increased risk affects family dynamics. As the demand for testing and counselling grows, health care providers will be faced with new challenges and dilemmas. A better understanding of genetics by the public is needed to mitigate deterministic attitudes that can lead to the neglect of health promotion. Also of concern are the socioeconomic implications of being identified as having a high risk for heritable cancer and the dangers inherent in using genetics to explain sociological phenomena. Health care providers must take the lead in ensuring that developments in genetics are used to the benefit of all. PMID:8630835

  5. Induction of KIAA1199/CEMIP is associated with colon cancer phenotype and poor patient survival.

    PubMed

    Fink, Stephen P; Myeroff, Lois L; Kariv, Revital; Platzer, Petra; Xin, Baozhong; Mikkola, Debra; Lawrence, Earl; Morris, Nathan; Nosrati, Arman; Willson, James K V; Willis, Joseph; Veigl, Martina; Barnholtz-Sloan, Jill S; Wang, Zhenghe; Markowitz, Sanford D

    2015-10-13

    Genes induced in colon cancer provide novel candidate biomarkers of tumor phenotype and aggressiveness. We originally identified KIAA1199 (now officially called CEMIP) as a transcript highly induced in colon cancer: initially designating the transcript as Colon Cancer Secreted Protein 1. We molecularly characterized CEMIP expression both at the mRNA and protein level and found it is a secreted protein induced an average of 54-fold in colon cancer. Knockout of CEMIPreduced the ability of human colon cancer cells to form xenograft tumors in athymic mice. Tumors that did grow had increased deposition of hyaluronan, linking CEMIP participation in hyaluronan degradation to the modulation of tumor phenotype. We find CEMIP mRNA overexpression correlates with poorer patient survival. In stage III only (n = 31) or in combined stage II plus stage III colon cancer cases (n = 73), 5-year overall survival was significantly better (p = 0.004 and p = 0.0003, respectively) among patients with low CEMIP expressing tumors than those with high CEMIP expressing tumors. These results demonstrate that CEMIP directly facilitates colon tumor growth, and high CEMIP expression correlates with poor outcome in stage III and in stages II+III combined cohorts. We present CEMIP as a candidate prognostic marker for colon cancer and a potential therapeutic target.

  6. Linear Discriminant Functions in Connection with the micro-RNA Diagnosis of Colon Cancer.

    PubMed

    Nikas, Jason B; Low, Walter C

    2012-01-01

    Early detection (localized stage) of colon cancer is associated with a five-year survival rate of 91%. Only 39% of colon cancers, however, are diagnosed at that early stage. Early and accurate diagnosis, therefore, constitutes a critical need and a decisive factor in the clinical treatment of colon cancer and its success. In this study, using supervised linear discriminant analysis, we have developed three diagnostic biomarker models that-based on global micro-RNA expression analysis of colonic tissue collected during surgery-can discriminate with a perfect accuracy between subjects with colon cancer (stages II-IV) and normal healthy subjects. We developed our three diagnostic biomarker models with 57 subjects [40 with colon cancer (stages II-IV) and 17 normal], and we validated them with 39 unknown (new and different) subjects [28 with colon cancer (stages II-IV) and 11 normal]. For all three diagnostic models, both the overall sensitivity and specificity were 100%. The nine most significant micro-RNAs identified, which comprise the input variables to the three linear discriminant functions, are associated with genes that regulate oncogenesis, and they play a paramount role in the development of colon cancer, as evidenced in the tumor tissue itself. This could have a significant impact in the fight against this disease, in that it may lead to the development of an early serum or blood diagnostic test based on the detection of those nine key micro-RNAs.

  7. Activation of TIM1 induces colon cancer cell apoptosis via modulating Fas ligand expression.

    PubMed

    Wang, Hao; Zhang, Xueyan; Sun, Wenjing; Hu, Xiaocui; Li, Xiaolin; Fu, Songbin; Liu, Chen

    2016-04-29

    The pathogenesis of colon cancer is unclear. It is proposed that TIM1 has an association with human cancer. The present study aims to investigate the role of TIM1 activation in the inhibition of human colon cancer cells. In this study, human colon cancer cell line, HT29 and T84 cells were cultured. The expression of TIM1 was assessed by real time RT-PCR and Western blotting. The TIM1 on the cancer cells was activated in the culture by adding recombinant TIM4. The chromatin structure at the FasL promoter locus was assessed by chromatin immunoprecipitation. The apoptosis of the cancer cells was assessed by flow cytometry. The results showed that human colon cancer cell lines, HT29 cells and T84 cells, expressed TIM1. Activation of TIM1 by exposing the cells to TIM4 significantly increased the frequency of apoptotic colon cancer cells. The expression of FasL was increased in the cancer cells after treating by TIM4. Blocking Fas or FasL abolished the exposure to TIM4-induced T84 cell apoptosis. In conclusion, HT29 cells and T84 cells express TIM1; activation TIM1 can induce the cancer cell apoptosis. TIM1 may be a novel therapeutic target of colon cancer.

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

    PubMed

    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.

  9. Up-regulation of Tim-3 is associated with poor prognosis of patients with colon cancer.

    PubMed

    Zhou, Encheng; Huang, Qing; Wang, Ji; Fang, Chengfeng; Yang, Leilei; Zhu, Min; Chen, Jianhui; Chen, Lihua; Dong, Milian

    2015-01-01

    Tim-3 (T cell immunoglobulin and mucin domain 3), belonging to the member of the novel Tim family, has been confirmed that it plays a critical negative role in regulating the immune responses against viral infection and carcinoma. Recently, it has also been reported that the over-expression of Tim-3 is associated with poor prognosis in solid tumors. However, the role of Tim-3 in colorectal cancer remains largely unknown. In the current study, we aim to investigate the expression of Tim-3 in colorectal carcinoma and discuss the relationship between Tim-3 expression and colon cancer prognosis, thus speculating the possible role of Tim-3 in colon cancer progression. Colon cancer tissues and paired normal tissue were obtained from 201 patients with colon cancer for preparation of tissue microarray. Tim-3 expression was evaluated by immunohistochemical staining. The Tim-3 expression level was evaluated by q-RT-PCR, western blot and immunocytochemistry in four colon cancer cell lines (HT-29, HCT116, LoVo, SW620). Tim-3 was expressed in 92.5% tumor tissue samples and 86.5% corresponding normal tissue samples. Expression of Tim-3 was significantly higher in tumor tissues than in normal tissues (P < 0.0001). Tim-3 expression in colon cancer tissues is in correlation with colon cancer lymphatic metastasis and TNM (P < 0.0001). Multivariate analysis demonstrated that Tim-3 expression could be a potential independent prognostic factor for colon cancer patients (P < 0.0001). Kaplan-Meier survival analysis result showed that patients with higher Tim-3 expression had a significantly shorter survival time than those with lower Tim-3 expression patients. Our results indicated that Tim-3 might participate in the tumorgenesis of colon cancer and Tim-3 expression might be a potential independent prognostic factor for patients with colorectal cancer.

  10. Predicted Vitamin D Status and Colon Cancer Recurrence and Mortality in CALGB 89803 (Alliance).

    PubMed

    Fuchs, M A; Yuan, C; Sato, K; Niedzwiecki, D; Ye, X; Saltz, L B; Mayer, R J; Mowat, R B; Whittom, R; Hantel, A; Benson, A; Atienza, D; Messino, M; Kindler, H; Venook, A; Innocenti, F; Warren, R S; Bertagnolli, M M; Ogino, S; Giovannucci, E L; Horvath, E; Meyerhardt, J A; Ng, K

    2017-03-15

    Observational studies suggest that higher levels of 25-hydroxyvitamin D 3 (25(OH)D) are associated with a reduced risk of colorectal cancer and improved survival of colorectal cancer patients. However, the influence of vitamin D status on cancer recurrence and survival of patients with stage III colon cancer is unknown.

  11. An integrated microfluidic system for screening of phage-displayed peptides specific to colon cancer cells and colon cancer stem cells.

    PubMed

    Che, Yu-Jui; Wu, Huei-Wen; Hung, Lien-Yu; Liu, Ching-Ann; Chang, Hwan-You; Wang, Kuan; Lee, Gwo-Bin

    2015-09-01

    Affinity reagents recognizing biomarkers specifically are essential components of clinical diagnostics and target therapeutics. However, conventional methods for screening of these reagents often have drawbacks such as large reagent consumption, the labor-intensive or time-consuming procedures, and the involvement of bulky or expensive equipment. Alternatively, microfluidic platforms could potentially automate the screening process within a shorter period of time and reduce reagent and sample consumption dramatically. It has been demonstrated recently that a subpopulation of tumor cells known as cancer stem cells possess high drug resistance and proliferation potential and are regarded as the main cause of metastasis. Therefore, a peptide that recognizes cancer stem cells and differentiates them from other cancer cells will be extremely useful in early diagnosis and target therapy. This study utilized M13 phage display technology to identify peptides that bind, respectively, to colon cancer cells and colon cancer stem cells using an integrated microfluidic system. In addition to positive selection, a negative selection process was integrated on the chip to achieve the selection of peptides of high affinity and specificity. We successfully screened three peptides specific to colon cancer cells and colon cancer stem cells, namely, HOLC-1, HOLC-2, and COLC-1, respectively, and their specificity was measured by the capture rate between target, control, and other cell lines. The capture rates are 43.40 ± 7.23%, 45.16 ± 7.12%, and 49.79 ± 5.34% for colon cancer cells and colon cancer stem cells, respectively, showing a higher specificity on target cells than on control and other cell lines. The developed technique may be promising for early diagnosis of cancer cells and target therapeutics.

  12. Benefits of Recurrent Colonic Stent Insertion in a Patient with Advanced Gastric Cancer with Carcinomatosis Causing Colonic Obstruction

    PubMed Central

    Park, Semi; Shin, Sang Joon; Ahn, Joong Bae; Jeung, Hei-Cheul; Rha, Sun Young; Lee, Sang Kil

    2009-01-01

    Malignant obstruction develops frequently in advanced gastric cancer. Although it is primarily the gastric outlet that is obstructed, there are occasional reports of colonic obstruction. Treating intestinal obstruction usually requires emergency surgery or stent insertion. There are several kinds of complications with stent insertion, such as bowel perforation, stent migration, bleeding, abdominal pain and reobstruction. Nevertheless, endoscopic stent insertion could be a better treatment than emergency surgery in cases of malignant bowel obstruction in cancer patients with poor performance status. We report a case of advanced gastric cancer with carcinomatosis in which a recurrent colonic stent was inserted at the same site because of cancer growth into the stent. The patient maintained a good condition for chemotherapy, thus improving their chances for survival. PMID:19430568

  13. Hereditary cancer syndromes in Latino populations: genetic characterization and surveillance guidelines.

    PubMed

    Cruz-Correa, Marcia; Pérez-Mayoral, Julyann; Dutil, Julie; Echenique, Miguel; Mosquera, Rafael; Rivera-Román, Keila; Umpierre, Sharee; Rodriguez-Quilichini, Segundo; Gonzalez-Pons, Maria; Olivera, Myrta I; Pardo, Sherly

    2017-01-01

    Hereditary cancer predisposition syndromes comprise approximately 10% of diagnosed cancers; however, familial forms are believed to account for up to 30% of some cancers. In Hispanics, the most commonly diagnosed hereditary cancers include colorectal cancer syndromes such as, Lynch Syndrome, Familial Adenomatous Polyposis, and hereditary breast and ovarian cancer syndromes. Although the incidence of hereditary cancers is low, patients diagnosed with hereditary cancer syndromes are at high-risk for developing secondary cancers. Furthermore, the productivity loss that occurs after cancer diagnosis in these high-risk patients has a negative socio-economic impact. This review summarizes the genetic basis, phenotype characteristics, and the National Comprehensive Cancer Network's screening, testing, and surveillance guidelines for the leading hereditary cancer syndromes. The aim of this review is to promote a better understanding of cancer genetics and genetic testing in Hispanic patients.

  14. Mast Cell Targeted Chimeric Toxin Can Be Developed as an Adjunctive Therapy in Colon Cancer Treatment.

    PubMed

    Wang, Shan; Li, Linmei; Shi, Renren; Liu, Xueting; Zhang, Junyan; Zou, Zehong; Hao, Zhuofang; Tao, Ailin

    2016-03-11

    The association of colitis with colorectal cancer has become increasingly clear with mast cells being identified as important inflammatory cells in the process. In view of the relationship between mast cells and cancer, we studied the effect and mechanisms of mast cells in the development of colon cancer. Functional and mechanistic insights were gained from ex vivo and in vivo studies of cell interactions between mast cells and CT26 cells. Further evidence was reversely obtained in studies of mast cell targeted Fcε-PE40 chimeric toxin. Experiments revealed mast cells could induce colon tumor cell proliferation and invasion. Cancer progression was found to be related to the density of mast cells in colonic submucosa. The activation of MAPK, Rho-GTPase, and STAT pathways in colon cancer cells was triggered by mast cells during cell-to-cell interaction. Lastly, using an Fcε-PE40 chimeric toxin we constructed, we confirmed the promoting effect of mast cells in development of colon cancer. Mast cells are a promoting factor of colon cancer and thus also a potential therapeutic target. The Fcε-PE40 chimeric toxin targeting mast cells could effectively prevent colon cancer in vitro and in vivo. Consequently, these data may demonstrate a novel immunotherapeutic approach for the treatment of tumors.

  15. Associations of Probiotics with Vitamin D and Leptin Receptors and their Effects on Colon Cancer.

    PubMed

    Ranji, Peyman; Akbarzadeh, Abolfazl; Rahmati-Yamchi, Mohammad

    2015-01-01

    Colorectal cancer (CRC) is one of most common causes of cancer-related death worldwide. Recent studies have suggested that microbial and environmental factors including diet and lifestyle can impact on colon cancer development. Vitamin D deficiency and dysfunction of vitamin D receptor (VDR) also correlate with colon cancer. Moreover, leptin, a 16-kDa polypeptide, participates in the regulation of food intake and is associated with other environmental factors affecting colon cancer through the leptin receptor. Altered levels of serum leptin and patterns of expression of its receptor (LPR) may be observed in human colon tumours. Furthermore, the collected data from in vitro and in vivo studies have indicated that consuming probiotic non-pathogenic lactic acid bacteria have beneficial effects on colon cancer. Probiotics, inflammation and vitamin D/VDR have been correlated with leptin and its receptor and are also with colon cancer. Thus, in this paper, we review recent progress on the roles of probiotic, vitamin D/VDR and leptin/LPR in inflammation and colon cancer.

  16. Mast Cell Targeted Chimeric Toxin Can Be Developed as an Adjunctive Therapy in Colon Cancer Treatment

    PubMed Central

    Wang, Shan; Li, Linmei; Shi, Renren; Liu, Xueting; Zhang, Junyan; Zou, Zehong; Hao, Zhuofang; Tao, Ailin

    2016-01-01

    The association of colitis with colorectal cancer has become increasingly clear with mast cells being identified as important inflammatory cells in the process. In view of the relationship between mast cells and cancer, we studied the effect and mechanisms of mast cells in the development of colon cancer. Functional and mechanistic insights were gained from ex vivo and in vivo studies of cell interactions between mast cells and CT26 cells. Further evidence was reversely obtained in studies of mast cell targeted Fcε-PE40 chimeric toxin. Experiments revealed mast cells could induce colon tumor cell proliferation and invasion. Cancer progression was found to be related to the density of mast cells in colonic submucosa. The activation of MAPK, Rho-GTPase, and STAT pathways in colon cancer cells was triggered by mast cells during cell-to-cell interaction. Lastly, using an Fcε-PE40 chimeric toxin we constructed, we confirmed the promoting effect of mast cells in development of colon cancer. Mast cells are a promoting factor of colon cancer and thus also a potential therapeutic target. The Fcε-PE40 chimeric toxin targeting mast cells could effectively prevent colon cancer in vitro and in vivo. Consequently, these data may demonstrate a novel immunotherapeutic approach for the treatment of tumors. PMID:26978404

  17. Activation of ERK signaling and induction of colon cancer cell death by piperlongumine.

    PubMed

    Randhawa, H; Kibble, K; Zeng, H; Moyer, M P; Reindl, K M

    2013-09-01

    Piperlongumine (PPLGM) is a bioactive compound isolated from long peppers that shows selective toxicity towards a variety of cancer cell types including colon cancer. The signaling pathways that lead to cancer cell death in response to PPLGM exposure have not been previously identified. Our objective was to identify the intracellular signaling mechanisms by which PPLGM leads to enhanced colon cancer cell death. We found that PPLGM inhibited the growth of colon cancer cells in time- and concentration-dependent manners, but was not toxic toward normal colon mucosal cells at concentrations below 10 μM. Acute (0-60 min) and prolonged (24h) exposure of HT-29 cells to PPLGM resulted in phosphorylation of ERK. To investigate whether ERK signaling was involved in PPLGM-mediated cell death, we treated HT-29 cells with the MEK inhibitor U0126, prior to treating with PPLGM. We found that U0126 attenuated PPLGM-induced activation of ERK and partially protected against PPLGM-induced cell death. These results suggest that PPLGM works, at least in part, through the MEK/ERK pathway to result in colon cancer cell death. A more thorough understanding of the molecular mechanisms by which PPLGM induces colon cancer cell death will be useful in developing therapeutic strategies to treat colon cancer.

  18. Pneumocystis jiroveci pneumonia and colonization in patients with advanced lung cancer

    PubMed Central

    TOGASHI, YOSUKE; MASAGO, KATSUHIRO; ITO, YUTAKA; SAKAMORI, YUICHI; OKUDA, CHIYUKI; FUKUHARA, AKIKO; NAGAI, HIROKI; KIM, YOUNG HAK; MISHIMA, MICHIAKI

    2013-01-01

    Pneumocystis jiroveci pneumonia (PCP) has long been recognized as a cause of mortality in immuno-compromised populations, including those with advanced lung cancer. Although Pneumocystis colonization has only recently been described due to the development of more sensitive molecular techniques, including polymerase chain reaction (PCR), it is unknown whether Pneumocystis colonization leads to the development of PCP. In the present study, we aimed to determine the prevalence of Pneumocystis colonization in advanced lung cancer patients. Furthermore, the association between PCP and Pneumocystis colonization was also investigated. Advanced lung cancer patients with no indication of PCP were evaluated to determine the prevalence of Pneumocystis colonization. We analyzed their oral wash (OW) samples and retrospectively evaluated advanced lung cancer patients with PCP by analyzing their sections of formalin-fixed, paraffin-embedded lung tissues obtained following a diagnosis of lung cancer. Pneumocystis colonization was determined by a PCR test for Pneumocystis jiroveci (P. jiroveci). No P. jiroveci was detected by PCR in the OW samples of 47 advanced lung cancer patients with no indication of PCP, or in the lung tissues of four advanced lung cancer patients with PCP. These results indicate that PCP is not associated with Pneumocystis colonization in advanced lung cancer patients, although this study is limited since this was a cross-sectional and retrospective study. PMID:23420670

  19. Galangin induces human colon cancer cell death via the mitochondrial dysfunction and caspase-dependent pathway.

    PubMed

    Ha, Tae Kwun; Kim, Mi Eun; Yoon, Ju Hwa; Bae, Sung Jin; Yeom, Jihye; Lee, Jun Sik

    2013-09-01

    Galangin is a member of flavonols and found in Alpinia officinarum, galangal root, and propolis. Previous studies have demonstrated that galangin has anti-cancer effects on several cancers, including melanoma, hepatoma, and leukaemia cells. However, anti-cancer activity of galangin on human colon cancer has not been established yet. In this study, we investigated the anti-cancer effects of galangin on two types of human colon cancer cells (HCT-15 and HT-29). We found that galangin induced apoptosis and DNA condensation of human colon cancer cells in a dose-dependent manner. We also determined that galangin increased the activation of caspase-3 and -9, and release of apoptosis inducing factor from the mitochondria into the cytoplasm by Western blot analysis. In addition, galangin induced human colon cancer cell death through the alteration of mitochondria membrane potential and dysfunction. These results suggest that galangin induces apoptosis of HCT-15 and HT-29 human colon cancer cells and may prove useful in the development of therapeutic agents for human colon cancer.

  20. Guanylyl cyclase C signaling axis and colon cancer prevention

    PubMed Central

    Pattison, Amanda M; Merlino, Dante J; Blomain, Erik S; Waldman, Scott A

    2016-01-01

    Colorectal cancer (CRC) is a major cause of cancer-related mortality and morbidity worldwide. While improved treatments have enhanced overall patient outcome, disease burden encompassing quality of life, cost of care, and patient survival has seen little benefit. Consequently, additional advances in CRC treatments remain important, with an emphasis on preventative measures. Guanylyl cyclase C (GUCY2C), a transmembrane receptor expressed on intestinal epithelial cells, plays an important role in orchestrating intestinal homeostatic mechanisms. These effects are mediated by the endogenous hormones guanylin (GUCA2A) and uroguanylin (GUCA2B), which bind and activate GUCY2C to regulate proliferation, metabolism and barrier function in intestine. Recent studies have demonstrated a link between GUCY2C silencing and intestinal dysfunction, including tumorigenesis. Indeed, GUCY2C silencing by the near universal loss of its paracrine hormone ligands increases colon cancer susceptibility in animals and humans. GUCY2C’s role as a tumor suppressor has opened the door to a new paradigm for CRC prevention by hormone replacement therapy using synthetic hormone analogs, such as the FDA-approved oral GUCY2C ligand linaclotide (Linzess™). Here we review the known contributions of the GUCY2C signaling axis to CRC, and relate them to a novel clinical strategy targeting tumor chemoprevention. PMID:27688649

  1. [Pancreatic-duodenectomy for invasive colon cancer in a patient with Lynch syndrome. Case report.].

    PubMed

    Vergara-Fernández, O; Zamora-Valdés, D; Rodríguez-Zentner, H A; Tapia, H; Sánchez-Fernández, N; Gamboa-Domínguez, A; Medina-Franco, H; Chan-Núñez, C

    2009-01-01

    Despite the screening efforts in the general population and particularly in families with hereditary colon cancer, locally advanced colon cancer remains a common clinical problem. In block resection is considered mainstay therapy in these patients. The aim of this report is to present a case of right-sided colon cancer with a medullar phenotype invading the duodenum treated through in block resection. A case of a 54-year-old male with a family history of colon and pancreatic cancer with lower gastrointestinal tract bleeding is presented. Colonoscopy and computed tomography scan showed a tumor in the colonic hepatic flexure invading the duodenum. The patient underwent an in block resection of the right colon, duodenum, pancreas and antrum. The histopathological study showed a T4N0M0 adenocarcinoma invading the duodenum, pancreas and antrum with negative margins. His postoperative evolution was complicated with a pancreatic fistula, which resolved with conservative measures. In conclusion, in block resection is the treatment of choice for locally advanced colon cancer with invasion to duodenum and pancreas and should be performed in high-volume centers familiar with this type of procedures. Key words: pancreaticoduodenectomy, colon cancer, Lynch syndrome, pancreas, surgery, Mexico.

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

    SciTech Connect

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

    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

  3. Decorin in Human Colon Cancer: Localization In Vivo and Effect on Cancer Cell Behavior In Vitro.

    PubMed

    Nyman, Marie C; Sainio, Annele O; Pennanen, Mirka M; Lund, Riikka J; Vuorikoski, Sanna; Sundström, Jari T T; Järveläinen, Hannu T

    2015-09-01

    Decorin is generally recognized as a tumor suppressing molecule. Nevertheless, although decorin has been shown to be differentially expressed in malignant tissues, it has often remained unclear whether, in addition to non-malignant stromal cells, cancer cells also express it. Here, we first used two publicly available databases to analyze the current information about decorin expression and immunoreactivity in normal and malignant human colorectal tissue samples. The analyses demonstrated that decorin expression and immunoreactivity may vary in cancer cells of human colorectal tissues. Therefore, we next examined decorin expression in normal, premalignant and malignant human colorectal tissues in more detail using both in situ hybridization and immunohistochemistry for decorin. Our results invariably demonstrate that malignant cells within human colorectal cancer tissues are devoid of both decorin mRNA and immunoreactivity. Identical results were obtained for cells of neuroendocrine tumors of human colon. Using RT-qPCR, we showed that human colon cancer cell lines are also decorin negative, in accordance with the above in vivo results. Finally, we demonstrate that decorin transduction of human colon cancer cell lines causes a significant reduction in their colony forming capability. Thus, strategies to develop decorin-based adjuvant therapies for human colorectal malignancies are highly rational.

  4. Engineering plasmonic nanorod arrays for colon cancer marker detection.

    PubMed

    Dodson, Stephanie L; Cao, Cuong; Zaribafzadeh, Hamed; Li, Shuzhou; Xiong, Qihua

    2015-01-15

    Engineering plasmonic nanomaterials or nanostructures towards ultrasensitive biosensing for disease markers or pathogens is of high importance. Here we demonstrate a systematic approach to tailor effective plasmonic nanorod arrays by combining both comprehensive numerical discrete dipole approximations (DDA) simulation and transmission spectroscopy experiments. The results indicate that 200×50 nm nanorod arrays with 300×500 nm period provide the highest figure of merit (FOM) of 2.4 and a sensitivity of 310 nm/RIU. Furthermore, we demonstrate the use of nanorod arrays for the detection of single nucleotide polymorphism in codon 12 of the K-ras gene that are frequently occurring in early stages of colon cancer, with a sensitivity down to 10 nM in the presence of 100-fold higher concentration of the homozygous genotypes. Our work shows significant potential of nanorod arrays towards point-of-care applications in diagnosis and clinical studies.

  5. Recent advances in oral anticancer agents for colon cancer.

    PubMed

    Shukla, Raj Kumar

    2013-12-01

    To provide therapeutic alternatives to intravenous colon chemotherapy major recent research is focusing on the development of oral chemotherapeutic agents with the intention to improve the quality of life of patients. Initially 5-fluorouracil was most commonly used for the treatment of colorectal cancer but currently oxaliplatin and irinotecan are also available. The majority of these new drugs are pyrimidines and their analogs. The rationale for using oral anticancer agents is discussed and new drugs, such as farnesyl protein transferase inhibitor S-1, rubitecan, ZD9331, MMI-166, eflornithine, sulindac, and oral camptothecin analogs, among others, are presented with the results of their preclinical and clinical developments. This article focuses on the advancement of clinical development and also discusses the relative merits and demerits of these agents. The accelerated approval of these agents by regulatory authorities is supported by survival benefit, response rate and time to progression.

  6. Adipokine regulation of colon cancer: adiponectin attenuates interleukin-6-induced colon carcinoma cell proliferation via STAT-3.

    PubMed

    Fenton, Jenifer I; Birmingham, Janette M

    2010-07-01

    Obesity results in increased circulating levels of specific adipokines, which are associated with colon cancer risk. The disease state is associated with increased leptin, insulin, IGF-1, and IL-6. Conversely, adiponectin levels are decreased in obese individuals. Previously, we demonstrated adipokine-enhanced cell proliferation in preneoplastic, but not normal, colon epithelial cells, demonstrating a differential effect of adipokines on colon cancer progression in vitro. Using a model of late stage carcinoma cancer cell, namely murine MC-38 colon carcinoma cells, we compared the effect of obesity-associated adipokines (leptin, insulin, IGF-1, and IL-6) on MC-38 cell proliferation and determined whether adiponectin (full length or globular) could modulate adipokine-induced cell proliferation. We show that insulin and IL-6, but not leptin and IGF-1, induce proliferation in MC-38 cells. Adiponectin treatment of MC-38 cells did not inhibit insulin-induced cell proliferation but did inhibit IL-6-induced cell proliferation by decreasing STAT-3 phosphorylation and activation. Nitric oxide (NO) production was increased in MC-38 cells treated with IL-6; co-treatment with adiponectin blocked IL-6-induced iNOS and subsequent NO production. These data are compared to previously reported findings from our laboratory using the YAMC (model normal colon epithelial cells) and IMCE (model preneoplastic) cells. The cell lines are utilized to construct a model summarizing the hormonal consequences of obesity and the impact on the differential regulation of colon epithelial cells along the continuum to carcinoma. These data, taken together, highlight mechanisms involved in obesity-associated cancers and may lead to potential-targeted therapies.

  7. Meat intake, cooking methods and risk of proximal colon, distal colon and rectal cancer: the Norwegian Women and Cancer (NOWAC) cohort study.

    PubMed

    Parr, Christine L; Hjartåker, Anette; Lund, Eiliv; Veierød, Marit B

    2013-09-01

    Red and processed meat intake is an established risk factor for colorectal cancer (CRC), but epidemiological evidence by subsite and sex is still limited. In the population-based Norwegian Women and Cancer cohort, we examined associations of meat intake with incident proximal colon, distal colon and rectal cancer, in 84,538 women who completed a validated food frequency questionnaire (FFQ) during 1996-1998 or 2003-2005 (baseline or exposure update) at age 41-70 years, with follow-up by register linkages through 2009. We also examined the effect of meat cooking methods in a subsample (n = 43,636). Multivariable hazard ratios (HRs) were estimated by Cox regression. There were 459 colon (242 proximal and 167 distal), and 215 rectal cancer cases with follow-up ≥ 1 (median 11.1) year. Processed meat intake ≥60 vs. <15 g/day was associated with significantly increased cancer risk in all subsites with HRs (95% confidence interval, CI) of 1.69 (1.05-2.72) for proximal colon, 2.13 (1.18-3.83) for distal colon and 1.71 (1.02-2.85) for rectal cancer. Regression calibration of continuous effects based on repeated 24-hr dietary recalls, indicated attenuation due to measurement errors in FFQ data, but corrected HRs were not statistically significant due to wider CIs. Our study did not support an association between CRC risk and intake of red meat, chicken, or meat cooking methods, but a high processed meat intake was associated with increased risk of proximal colon, distal colon and rectal cancer. The effect of processed meat was mainly driven by the intake of sausages.

  8. CacyBP/SIP promotes the proliferation of colon cancer cells.

    PubMed

    Zhai, Huihong; Shi, Yongquan; Chen, Xiong; Wang, Jun; Lu, Yuanyuan; Zhang, Faming; Liu, Zhengxiong; Lei, Ting; Fan, Daiming

    2017-01-01

    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.

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

    PubMed

    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 (P<0.001). The same results were got in colon 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).

  10. CacyBP/SIP promotes the proliferation of colon cancer cells

    PubMed Central

    Chen, Xiong; Wang, Jun; Lu, Yuanyuan; Zhang, Faming; Liu, Zhengxiong; Lei, Ting; Fan, Daiming

    2017-01-01

    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. PMID:28196083

  11. MicroRNA Profiles Discriminate among Colon Cancer Metastasis

    PubMed Central

    Drusco, Alessandra; Nuovo, Gerard J.; Zanesi, Nicola; Di Leva, Gianpiero; Pichiorri, Flavia; Volinia, Stefano; Fernandez, Cecilia; Antenucci, Anna; Costinean, Stefan; Bottoni, Arianna; Rosito, Immacolata A.; Liu, Chang-Gong; Burch, Aaron; Acunzo, Mario; Pekarsky, Yuri; Alder, Hansjuerg; Ciardi, Antonio; Croce, Carlo M.

    2014-01-01

    MicroRNAs are being exploited for diagnosis, prognosis and monitoring of cancer and other diseases. Their high tissue specificity and critical role in oncogenesis provide new biomarkers for the diagnosis and classification of cancer as well as predicting patients' outcomes. MicroRNAs signatures have been identified for many human tumors, including colorectal cancer (CRC). In most cases, metastatic disease is difficult to predict and to prevent with adequate therapies. The aim of our study was to identify a microRNA signature for metastatic CRC that could predict and differentiate metastatic target organ localization. Normal and cancer tissues of three different groups of CRC patients were analyzed. RNA microarray and TaqMan Array analysis were performed on 66 Italian patients with or without lymph nodes and/or liver recurrences. Data obtained with the two assays were analyzed separately and then intersected to identify a primary CRC metastatic signature. Five differentially expressed microRNAs (hsa-miR-21, -103, -93, -31 and -566) were validated by qRT-PCR on a second group of 16 American metastatic patients. In situ hybridization was performed on the 16 American patients as well as on three distinct commercial tissues microarray (TMA) containing normal adjacent colon, the primary adenocarcinoma, normal and metastatic lymph nodes and liver. Hsa-miRNA-21, -93, and -103 upregulation together with hsa-miR-566 downregulation defined the CRC metastatic signature, while in situ hybridization data identified a lymphonodal invasion profile. We provided the first microRNAs signature that could discriminate between colorectal recurrences to lymph nodes and liver and between colorectal liver metastasis and primary hepatic tumor. PMID:24921248

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

    PubMed

    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.

  13. Four microRNAs Signature for Survival Prognosis in Colon Cancer using TCGA Data

    PubMed Central

    Xu, Jian; Zhao, Jian; Zhang, Rui

    2016-01-01

    This study aims to develop microRNA expression signature for colon cancer survival prognosis based on the Cancer Genomic Common database. miRNAs levels between colon cancer and non-cancer tissues were screened by t-test (p < 0.05). Kaplan-Meier survival method was used to discriminate survival significant miRNAs, followed by miRNAs index accumulation to power the miRNAs-survival reliability. In the end, we test the selected miRNAs in HT126 colon cancer cells to validate its anti-cancer effect. The study identified a 84-miRNAs signature. Of the above 84 miRNAs, we got four miRNAs which were survival associated by using ROC curve method and Kaplan-Meier survival method (p < 0.001). The result showed that low risk group had quite a low death rate, the survival rate was over 80%. The high risk group had survival rate lower than 20%, which was also extremely lower than the overall survival rate. In the HT126 cells study, cell growth assay showed miR-130a sponge inhibited colon cancer cells growth and sensitized the anti-cancer drug effect of 5-FU to blocked cancer cell growth. We developed a prognostic 4-microRNA expression signature for colon cancer patient survival, and validated miR-130a sponge could sensitized 5-FU anti-cancer effect. PMID:27974852

  14. Role of pomegranate and citrus fruit juices in colon cancer prevention.

    PubMed

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

    2014-04-28

    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.

  15. Role of pomegranate and citrus fruit juices in colon cancer prevention

    PubMed Central

    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

  16. Green vegetables, red meat and colon cancer: chlorophyll prevents the cytotoxic and hyperproliferative effects of haem in rat colon.

    PubMed

    de Vogel, Johan; Jonker-Termont, Denise S M L; van Lieshout, Esther M M; Katan, Martijn B; van der Meer, Roelof

    2005-02-01

    Diets high in red meat and low in green vegetables are associated with increased colon cancer risk. This association might be partly due to the haem content of red meat. In rats, dietary haem is metabolized in the gut to a cytotoxic factor that increases colonic cytotoxicity and epithelial proliferation. Green vegetables contain chlorophyll, a magnesium porphyrin structurally analogous to haem. We studied whether green vegetables inhibit the unfavourable colonic effects of haem. First, rats were fed a purified control diet or purified diets supplemented with 0.5 mmol haem/kg, spinach (chlorophyll concentration 1.2 mmol/kg) or haem plus spinach (n = 8/group) for 14 days. In a second experiment we also studied a group that received haem plus purified chlorophyll (1.2 mmol/kg). Cytotoxicity of faecal water was determined with a bioassay and colonic epithelial cell proliferation was quantified in vivo by [methyl-(3)H]thymidine incorporation into newly synthesized DNA. Exfoliation of colonocytes was measured as the amount of rat DNA in faeces. In both studies haem increased cytotoxicity of the colonic contents approximately 8-fold and proliferation of the colonocytes almost 2-fold. Spinach or an equimolar amount of chlorophyll supplement in the haem diet inhibited these haem effects completely. Haem clearly inhibited exfoliation of colonocytes, an effect counteracted by spinach and chlorophyll. Finally, size exclusion chromatography showed that chlorophyll prevented formation of the cytotoxic haem metabolite. We conclude that green vegetables may decrease colon cancer risk because chlorophyll prevents the detrimental, cytotoxic and hyperproliferative colonic effects of dietary haem.

  17. Isolation and phenotypic characterization of cancer stem-like side population cells in colon cancer.

    PubMed

    Feng, Long; Wu, Jian-Bing; Yi, Feng-Ming

    2015-09-01

    Previous studies in cancer biology suggest that chemotherapeutic drug resistance and tumor relapse are driven by cells within a tumor termed 'cancer stem cells'. In the present study, a Hoechst 33342 dye exclusion technique was used to identify cancer stem‑like side population (SP) cells in colon carcinoma, which accounted for 3.4% of the total cell population. Following treatment with verapamil, the population of SP cells was reduced to 0.6%. In addition, the sorted SP cells exhibited marked multidrug resistance and enhanced cell survival rates compared with non‑SP cells. The SP cells were able to generate more tumor spheres and were CD133 positive. Subsequent biochemical analysis revealed that the levels of the adenosine triphosphate‑binding cassette sub‑family G member 2 transporter protein, B‑cell lymphoma anti‑apoptotic factor and autocrine production of interleukin‑4 were significantly enhanced in the colon cancer SP cells, which contributed to drug resistance, protection of the cells from apoptosis and tumor recurrence. Therefore, the findings suggested that treatment failure and colon tumorigenesis is dictated by a small population of SP cells, which indicate a potential target in future therapies.

  18. Human colon cancer HT-29 cell death responses to doxorubicin and Morus Alba leaves flavonoid extract.

    PubMed

    Fallah, S; Karimi, A; Panahi, G; Gerayesh Nejad, S; Fadaei, R; Seifi, M

    2016-03-31

    The mechanistic basis for the biological properties of Morus alba flavonoid extract (MFE) and chemotherapy drug of doxorubicin on human colon cancer HT-29 cell line death are unknown. The effect of doxorubicin and flavonoid extract on colon cancer HT-29 cell line death and identification of APC gene expression and PARP concentration of HT-29 cell line were investigated. The results showed that flavonoid extract and doxorubicin induce a dose dependent cell death in HT-29 cell line. MFE and doxorubicin exert a cytotoxic effect on human colon cancer HT-29 cell line by probably promoting or induction of apoptosis.

  19. Niclosamide inhibition of STAT3 synergizes with erlotinib in human colon cancer

    PubMed Central

    Shi, Lingyi; Zheng, Hailun; Hu, Wanle; Zhou, Bin; Dai, Xuanxuan; Zhang, Yi; Liu, Zhiguo; Wu, Xiaoping; Zhao, Chengguang; Liang, Guang

    2017-01-01

    Niclosamide, an anthelmintic drug approved by the US Food and Drug Administration against cestodes, is used to treat tapeworm infection. In this study, we show that niclosamide can potentially inhibit signal transducer and activator of transcription 3 (STAT3) in colon cancer cell lines. Combined inhibition of epidermal growth factor receptor and STAT3 by erlotinib and niclosamide synergistically induces apoptosis and antiproliferation in colon cancer cell lines. Our findings suggest that erlotinib and niclosamide combination provides an effective therapeutic approach to improving the prognosis of colon cancer. PMID:28367059

  20. PET-CT–Guided Surveillance of Head and Neck Cancers

    Cancer.gov

    Patients with advanced squamous cell carcinoma of the head and neck who underwent PET-CT–guided surveillance had fewer operations but similar overall survival rates to those of patients who underwent planned neck dissection.

  1. LINE-1 hypomethylation in normal colon mucosa is associated with poor survival in Chinese patients with sporadic colon cancer

    PubMed Central

    Wu, Yuchen; Li, Yiwei; Nie, Jia; Li, Dawei; Peng, Junjie; Lian, Peng; Li, Bin; Cai, Guoxiang; Li, Xinxiang; Cai, Sanjun

    2015-01-01

    Genetic and epigenetic pathways are not independent in colorectal cancer (CRC) carcinogenesis. We aimed to determine the influence of various molecular features on Chinese patients' colon cancer-specific survival (CCSS). Various genetic and epigenetic modifications were detected in paired tumor and normal mucosa tissue samples. The prognostic variables regarding patient CCSS were determined. Overall, 127 patients, including 83 males and 44 females, completed a median follow-up of 65 (3–85) months. A mean LINE-1 methylation rate of 64.62% (range, 9.45–86.93) was observed. Hypermethylation at the hMLH1 gene promoter was detected in 26 (20.47%) patients. KRAS was mutated in 52 (40.94%) patients. Sixteen (12.60%) patients were confirmed as microsatellite instability (MSI)-High, and 76 (59.84%) were found to have loss of heterozygosity at 18q. The LINE-1 methylation level, MSI status, perineural invasion and distant metastases were confirmed as independent prognostic factors for patient CCSS. A stratified survival analysis further revealed that certain subgroups of patients with LINE-1 hypomethylation had significantly worse survival (all p < 0.05). Our data revealed that both genetic and epigenetic abnormalities can concurrently exist during colonic tumorigenesis. As a global epigenetic change, LINE-1 hypomethylation in normal colon mucosa might be associated with a worse outcome in certain Chinese patients with colon cancer. PMID:26172297

  2. Comprehensive molecular characterization of human colon and rectal cancer.

    PubMed

    2012-07-18

    To characterize somatic alterations in colorectal carcinoma, we conducted a genome-scale analysis of 276 samples, analysing exome sequence, DNA copy number, promoter methylation and messenger RNA and microRNA expression. A subset of these samples (97) underwent low-depth-of-coverage whole-genome sequencing. In total, 16% of colorectal carcinomas were found to be hypermutated: three-quarters of these had the expected high microsatellite instability, usually with hypermethylation and MLH1 silencing, and one-quarter had somatic mismatch-repair gene and polymerase ε (POLE) mutations. Excluding the hypermutated cancers, colon and rectum cancers were found to have considerably similar patterns of genomic alteration. Twenty-four genes were significantly mutated, and in addition to the expected APC, TP53, SMAD4, PIK3CA and KRAS mutations, we found frequent mutations in ARID1A, SOX9 and FAM123B. Recurrent copy-number alterations include potentially drug-targetable amplifications of ERBB2 and newly discovered amplification of IGF2. Recurrent chromosomal translocations include the fusion of NAV2 and WNT pathway member TCF7L1. Integrative analyses suggest new markers for aggressive colorectal carcinoma and an important role for MYC-directed transcriptional activation and repression.

  3. Acetylation modification regulates GRP78 secretion in colon cancer cells

    PubMed Central

    Li, Zongwei; Zhuang, Ming; Zhang, Lichao; Zheng, Xingnan; Yang, Peng; Li, Zhuoyu

    2016-01-01

    High glucose-regulated protein 78 (GRP78) expression contributes to the acquisition of a wide range of phenotypic cancer hallmarks, and the pleiotropic oncogenic functions of GRP78 may result from its diverse subcellular distribution. Interestingly, GRP78 has been reported to be secreted from solid tumour cells, participating in cell-cell communication in the tumour microenvironment. However, the mechanism underlying this secretion remains elusive. Here, we report that GRP78 is secreted from colon cancer cells via exosomes. Histone deacetylase (HDAC) inhibitors blocked GRP78 release by inducing its aggregation in the ER. Mechanistically, HDAC inhibitor treatment suppressed HDAC6 activity and led to increased GRP78 acetylation; acetylated GRP78 then bound to VPS34, a class III phosphoinositide-3 kinase, consequently preventing the sorting of GRP78 into multivesicular bodies (MVBs). Of note, we found that mimicking GRP78 acetylation by substituting the lysine at residue 633, one of the deacetylated sites of HDAC6, with a glutamine resulted in decreased GRP78 secretion and impaired tumour cell growth in vitro. Our study thus reveals a hitherto-unknown mechanism of GRP78 secretion and may also provide implications for the therapeutic use of HDAC inhibitors. PMID:27460191

  4. Comprehensive Molecular Characterization of Human Colon and Rectal Cancer

    PubMed Central

    2012-01-01

    Summary To characterize somatic alterations in colorectal carcinoma (CRC), we conducted genome-scale analysis of 276 samples, analyzing exome sequence, DNA copy number, promoter methylation, mRNA and microRNA expression. A subset (97) underwent low-depth-of-coverage whole-genome sequencing. 16% of CRC have hypermutation, three quarters of which have the expected high microsatellite instability (MSI), usually with hypermethylation and MLH1 silencing, but one quarter has somatic mismatch repair gene mutations. Excluding hypermutated cancers, colon and rectum cancers have remarkably similar patterns of genomic alteration. Twenty-four genes are significantly mutated. In addition to the expected APC, TP53, SMAD4, PIK3CA and KRAS mutations, we found frequent mutations in ARID1A, SOX9, and FAM123B/WTX. Recurrent copy number alterations include potentially drug-targetable amplifications of ERBB2 and newly discovered amplification of IGF2. Recurrent chromosomal translocations include fusion of NAV2 and WNT pathway member TCF7L1. Integrative analyses suggest new markers for aggressive CRC and important role for MYC-directed transcriptional activation and repression. PMID:22810696

  5. Variation in the CYP19A1 gene and risk of colon and rectal cancer.

    PubMed

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

    2011-07-01

    CYP19A1, or aromatase, influences estrogen-metabolizing enzymes and may influence cancer risk. We examine variation in the CYP19A1 gene and risk of colorectal cancer using data from population-based case-control studies (colon n = 1,574 cases, 1,970 controls; rectal n = 791 cases, 999 controls). Four SNPs were statistically significantly associated with colon cancer and four were associated with rectal cancer. After adjustment for multiple comparisons, the AA genotype of rs12591359 was associated with an increased risk of colon cancer (OR 1.44 95% CI 1.16-1.80) and the AA genotype of rs2470144 was associated with a reduced risk of rectal cancer (OR 0.65 95% CI 0.50-0.84). Variants of CYP19A1 were associated with CIMP+ and CIMP+/KRAS2-mutated tumors. CT/TT genotypes of rs1961177 were significantly associated with an increased likelihood of a MSI+ colon tumor (OR 1.77 95% CI 1.26-2.37). We observed statistically significant interactions between genetic variation in NFκB1 and CYP19A1 for both colon and rectal cancer. Our data suggest the importance of CYP19A1 in the development of colon and rectal cancer and that estrogen may influence risk through an inflammation-related mechanism.

  6. Terpenoids as anti-colon cancer agents - A comprehensive review on its mechanistic perspectives.

    PubMed

    Sharma, Sharada H; Thulasingam, Senthilkumar; Nagarajan, Sangeetha

    2017-01-15

    Multistep model of colon carcinogenesis has provided the framework to advance our understanding of the molecular basis of colon cancer. This multistage process of carcinogenesis takes a long period to transform from a normal epithelial cell to invasive carcinoma. Thus, it provides enough time to intervene the process of carcinogenesis especially through dietary modification. In spite of the in-depth understanding of the colon cancer etiology and pathophysiology and its association with diet, colon cancer remains a major cause of cancer mortality worldwide. Phytochemicals and their derivatives are gaining attention in cancer prevention and treatment strategies because of cancer chemotherapy associated adverse effects. Being the largest group of phytochemicals traditionally used for medicinal purpose in India and China, terpenoids are recently being explored as anticancer agents. Anticancer properties of terpenoids are associated with various mechanisms like counteraction of oxidative stress, potentiating endogenous antioxidants, improving detoxification potential, disrupting cell survival pathways and inducing apoptosis. This review gives a comprehensive idea of naturally occurring terpenoids as useful agents for the prevention of colon cancer with reference to their classes, sources and molecular targets. Based on the explored molecular targets further research in colon cancer chemoprevention is warranted.

  7. Associations between trans fatty acid consumption and colon cancer among Whites and African Americans in the North Carolina colon cancer study I.

    PubMed

    Vinikoor, Lisa C; Satia, Jessie A; Schroeder, Jane C; Millikan, Robert C; Martin, Christopher F; Ibrahim, Joseph G; Sandler, Robert S

    2009-01-01

    Disparities in incidence and mortality rates of colon cancer exist between Whites and African Americans. Prior studies examined the association between trans fatty acid consumption and colorectal cancer, but none assessed this possible relationship within a large study population of African Americans and Whites. Using data from a population-based, case-control study in North Carolina, we investigated this association with attention to possible racial differences. Cases and matched controls were queried on demographic characteristics, lifestyle factors, medical history, and diet. Cases reported higher daily consumption (g/day) of trans fatty acids (mean = 5.9, SD = 2.9, median = 5.5, IQR = 3.8-7.5) compared to controls (mean = 5.2, SD = 2.4, median = 4.7, IQR = 3.5-6.4). Energy-adjusted trans fatty acid consumption was not associated with colon cancer. Compared to participants in the lowest quartile of consumption, those in the highest quartile had an adjusted odds ratio of 1.01 (95% confidence interval 0.69, 1.49) for Whites and 0.99 (95% confidence interval 0.61, 1.62) for African Americans. No association was found between increased consumption of trans fatty acid and specific tumor location (proximal or distal colon). In conclusion, trans fatty acid consumption is not associated with colon cancer and does not contribute to disparities in colon cancer rates.

  8. Detection of elements and trace elements in endoscopy biopsies of colonic mucosa in normal and high risks colon cancer patients

    NASA Astrophysics Data System (ADS)

    Buoso, M. C.; Fazinic, S.; Galassini, S.; Lecis, P. E.; Moschini, G.; Makarewicz, M.; Naccarato, R.; Ogris, R.; Shao, H. R.; Sturniolo, G. C.; Valkovic, V.

    1991-05-01

    In the present study efforts are made to obtain a correlation between the trace element (TE) levels in patients and the presence of digestive cancer. The aim of the study is to detect selenium (Se), zinc (Zn) and other TE concentrations in different segments of colonic mucosa and to find out if there is any difference between the normal and pathological colonic mucosa. The concentration data (averages, standard deviations and ranges) obtained by neutron activation analysis and proton induced X-ray emission are presented and the data distribution is analyzed.

  9. Association between CYP7A1 and the risk of proximal colon cancer in Japanese.

    PubMed

    Ito, Hidemi; Matsuo, Keitaro; Hosono, Satoyo; Watanabe, Miki; Kawase, Takakazu; Suzuki, Takeshi; Hirai, Takashi; Yatabe, Yasushi; Tanaka, Hideo; Tajima, Kazuo

    2010-01-01

    Bile acids have long been implicated in the etiology of colorectal carcinogenesis by their genotoxicity as well as cytotoxicity. Cholesterol 7-alfa-hydroxylase (CYP7A1) is the rate-limiting enzyme that converts cholesterol into cholesterol 7-alfa-hydroxycholesterol in the first step of the classical pathway of bile acid synthesis. Recently, an association between a polymorphism (-204A>C, rs3808607) in CYP7A1 and proximal colon cancer/adenoma has been reported, which was not observed with distal colon or rectal cancer/adenoma. In this case-control study, we examined the association between haplotypes of CYP7A1 and proximal or distal colon/rectal cancer risk in a Japanese population. Subjects were 96 cases of proximal colon cancer, 357 of distal colon/rectal cancer and 961 age- and sex-matched non-cancer controls at Aichi Cancer Center. We examined five loci, including rs3808607, and evaluated the impact of haplotype on risk. In locus-specific analyses, we saw no association with rs3808607 for any site. Haplotype analyses revealed that the TAAGG haplotype was positively associated with proximal colon cancer [confounder-adjusted odds ratio: 1.72 (95% confidence interval: 1.10-2.71), p=0.018] but not with distal colon and rectal cancer combined. This association was consistently observed in analyses stratified by potential confounders. Our results indicate that CYP7A1 plays a role in the carcinogenesis of colorectal cancer specifically in the proximal colon. Confirmation of this association in other epidemiologic studies and biological evaluation of the TAAGG haplotype are warranted.

  10. Anticancer effect of linalool via cancer-specific hydroxyl radical generation in human colon cancer

    PubMed Central

    Iwasaki, Kenichi; Zheng, Yun-Wen; Murata, Soichiro; Ito, Hiromu; Nakayama, Ken; Kurokawa, Tomohiro; Sano, Naoki; Nowatari, Takeshi; Villareal, Myra O; Nagano, Yumiko N; Isoda, Hiroko; Matsui, Hirofumi; Ohkohchi, Nobuhiro

    2016-01-01

    AIM To investigate the anticancer mechanisms of the monoterpenoid alcohol linalool in human colon cancer cells. METHODS The cytotoxic effect of linalool on the human colon cancer cell lines and a human fibroblast cell line was examined using the WST-8 assay. The apoptosis-inducing effect of linalool was measured using the terminal deoxynucleotidyl transferase dUTP nick-end labeling assay and flow cytometry with Annexin V. Oxidative stress was investigated by staining for diphenyl-1-pyrenylphosphine, which is a cellular lipid peroxidation marker, and electron spin resonance spectroscopy. Sixteen SCID mice xenografted with human cancer cells were randomized into 3 groups for in vivo analysis: control and low-dose and high-dose linalool groups. The control group was administered tap water orally every 3 d. The linalool treatment groups were administered 100 or 200 μg/kg linalool solution orally for the same period. All mice were sacrificed under anesthesia 21 d after tumor inoculation, and tumors and organs were collected for immunohistochemistry using an anti-4-hydroxynonenal antibody. Tumor weights were measured and compared between groups. RESULTS Linalool induced apoptosis of cancer cells in vitro, following the cancer-specific induction of oxidative stress, which was measured based on spontaneous hydroxyl radical production and delayed lipid peroxidation. Mice in the high-dose linalool group exhibited a 55% reduction in mean xenograft tumor weight compared with mice in the control group (P < 0.05). In addition, tumor-specific lipid peroxidation was observed in the in vivo model. CONCLUSION Linalool exhibited an anticancer effect via cancer-specific oxidative stress, and this agent has potential for application in colon cancer therapy. PMID:27956800

  11. Food consumption and cancer of the colon and rectum in north-eastern Italy.

    PubMed

    Bidoli, E; Franceschi, S; Talamini, R; Barra, S; La Vecchia, C

    1992-01-21

    The relation between dietary factors and the risk of colorectal cancer was investigated in a case-control study conducted in Pordenone province, North-eastern Italy, on 123 cases of colon cancer, 125 of rectal cancer and 699 controls admitted to hospital for acute, non-neoplastic or digestive disorders. Consistent positive associations were observed with more frequent consumption of bread (odds ratio, OR = 2.1 for colon and 2.2 for rectum for highest vs. lowest tertile), polenta (OR = 2.1 for colon, 1.9 for rectum), cheese (OR = 1.7 for colon, 1.8 for rectum) and eggs (2.5 for colon, 1.9 for rectum), whereas reduced ORs were observed in subjects reporting more frequent consumption of tomatoes (OR = 0.5 for colon and 0.4 for rectum). High consumption of margarine exerted a significant protection against cancer of the colon whereas high consumption of carrot spinach, whole-grain bread and pasta (favorably) and red meat (unfavorably) affected rectal cancer risk in particular. Thus the present study gives support for a protective effect associated with a fiber-rich or vegetable-rich diet, while it indicates that frequent consumption of refined starchy foods, eggs and fat-rich foods such as cheese and red meat is a risk factor for colo-rectal cancer.

  12. Modeling human colon cancer in rodents using a food-borne carcinogen, PhIP.

    PubMed

    Nakagama, Hitoshi; Nakanishi, Masako; Ochiai, Masako

    2005-10-01

    Animal models provide researchers with powerful tools to elucidate multistage mechanisms for cancer development and to gain further insights into the biological roles of various cancer-related genes in in vivo situations. As for colon cancer models in rodents, Apc-disrupted mice, including ApcMin, have been one of the most widely utilized animal models to dissect the molecular events implicated in the development of intestinal tumors. In rats, several models have been established using chemical carcinogens, including azoxymethane and 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine (PhIP). The former is a representative colon carcinogenic alkylating agent, and the latter a heterocyclic amine produced while cooking meat and fish, which people are exposed to in ordinary life. It is of great importance to note that PhIP preferentially targets the colon and prostate gland in male rats, and the mammary glands in female rats. Cancers in these three organs are common in Western countries and are currently increasing in Japan, where modern dietary habits are rapidly becoming more like those of the West. In the present article, the history of PhIP-induced colon cancer models in rodents, activation/detoxification mechanisms of PhIP with regard to the formation of PhIP-DNA adducts, mechanistic approaches to dissect the molecular events involved in the development of colon cancer by PhIP, and epidemiological evidence of human exposure to PhIP are overviewed. The induction of Paneth cell maturation/differentiation in PhIP-induced colon cancers, genetic traits affecting susceptibility to colon carcinogenesis, and the biological relevance of colon cancer models in rodents to studying human colon carcinogenesis are also discussed.

  13. Wisconsin’s Environmental Public Health Tracking Network: Information Systems Design for Childhood Cancer Surveillance

    PubMed Central

    Hanrahan, Lawrence P.; Anderson, Henry A.; Busby, Brian; Bekkedal, Marni; Sieger, Thomas; Stephenson, Laura; Knobeloch, Lynda; Werner, Mark; Imm, Pamela; Olson, Joseph

    2004-01-01

    In this article we describe the development of an information system for environmental childhood cancer surveillance. The Wisconsin Cancer Registry annually receives more than 25,000 incident case reports. Approximately 269 cases per year involve children. Over time, there has been considerable community interest in understanding the role the environment plays as a cause of these cancer cases. Wisconsin’s Public Health Information Network (WI-PHIN) is a robust web portal integrating both Health Alert Network and National Electronic Disease Surveillance System components. WI-PHIN is the information technology platform for all public health surveillance programs. Functions include the secure, automated exchange of cancer case data between public health–based and hospital-based cancer registrars; web-based supplemental data entry for environmental exposure confirmation and hypothesis testing; automated data analysis, visualization, and exposure–outcome record linkage; directories of public health and clinical personnel for role-based access control of sensitive surveillance information; public health information dissemination and alerting; and information technology security and critical infrastructure protection. For hypothesis generation, cancer case data are sent electronically to WI-PHIN and populate the integrated data repository. Environmental data are linked and the exposure–disease relationships are explored using statistical tools for ecologic exposure risk assessment. For hypothesis testing, case–control interviews collect exposure histories, including parental employment and residential histories. This information technology approach can thus serve as the basis for building a comprehensive system to assess environmental cancer etiology. PMID:15471739

  14. A novel web informatics approach for automated surveillance of cancer mortality trends.

    PubMed

    Tourassi, Georgia; Yoon, Hong-Jun; Xu, Songhua

    2016-06-01

    Cancer surveillance data are collected every year in the United States via the National Program of Cancer Registries (NPCR) and the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute (NCI). General trends are closely monitored to measure the nation's progress against cancer. The objective of this study was to apply a novel web informatics approach for enabling fully automated monitoring of cancer mortality trends. The approach involves automated collection and text mining of online obituaries to derive the age distribution, geospatial, and temporal trends of cancer deaths in the US. Using breast and lung cancer as examples, we mined 23,850 cancer-related and 413,024 general online obituaries spanning the timeframe 2008-2012. There was high correlation between the web-derived mortality trends and the official surveillance statistics reported by NCI with respect to the age distribution (ρ=0.981 for breast; ρ=0.994 for lung), the geospatial distribution (ρ=0.939 for breast; ρ=0.881 for lung), and the annual rates of cancer deaths (ρ=0.661 for breast; ρ=0.839 for lung). Additional experiments investigated the effect of sample size on the consistency of the web-based findings. Overall, our study findings support web informatics as a promising, cost-effective way to dynamically monitor spatiotemporal cancer mortality trends.

  15. A novel web informatics approach for automated surveillance of cancer mortality trends✩

    PubMed Central

    Tourassi, Georgia; Yoon, Hong-Jun; Xu, Songhua

    2016-01-01

    Cancer surveillance data are collected every year in the United States via the National Program of Cancer Registries (NPCR) and the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute (NCI). General trends are closely monitored to measure the nation's progress against cancer. The objective of this study was to apply a novel web informatics approach for enabling fully automated monitoring of cancer mortality trends. The approach involves automated collection and text mining of online obituaries to derive the age distribution, geospatial, and temporal trends of cancer deaths in the US. Using breast and lung cancer as examples, we mined 23,850 cancer-related and 413,024 general online obituaries spanning the timeframe 2008–2012. There was high correlation between the web-derived mortality trends and the official surveillance statistics reported by NCI with respect to the age distribution (ρ = 0.981 for breast; ρ = 0.994 for lung), the geospatial distribution (ρ = 0.939 for breast; ρ = 0.881 for lung), and the annual rates of cancer deaths (ρ = 0.661 for breast; ρ = 0.839 for lung). Additional experiments investigated the effect of sample size on the consistency of the web-based findings. Overall, our study findings support web informatics as a promising, cost-effective way to dynamically monitor spatiotemporal cancer mortality trends. PMID:27044930

  16. A novel web informatics approach for automated surveillance of cancer mortality trends

    SciTech Connect

    Tourassi, Georgia; Yoon, Hong -Jun; Xu, Songhua

    2016-04-01

    Cancer surveillance data are collected every year in the United States via the National Program of Cancer Registries (NPCR) and the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute (NCI). General trends are closely monitored to measure the nation’s progress against cancer. The objective of this study was to apply a novel web informatics approach for enabling fully automated monitoring of cancer mortality trends. The approach involves automated collection and text mining of online obituaries to derive the age distribution, geospatial, and temporal trends of cancer deaths in the US. Using breast and lung cancer as examples, we mined 23,850 cancer-related and 413,024 general online obituaries spanning the timeframe 2008–2012. There was high correlation between the web-derived mortality trends and the official surveillance statistics reported by NCI with respect to the age distribution (ρ = 0.981 for breast; ρ = 0.994 for lung), the geospatial distribution (ρ = 0.939 for breast; ρ = 0.881 for lung), and the annual rates of cancer deaths (ρ = 0.661 for breast; ρ = 0.839 for lung). Additional experiments investigated the effect of sample size on the consistency of the web-based findings. Altogether, our study findings support web informatics as a promising, cost-effective way to dynamically monitor spatiotemporal cancer mortality trends.

  17. A novel web informatics approach for automated surveillance of cancer mortality trends

    DOE PAGES

    Tourassi, Georgia; Yoon, Hong -Jun; Xu, Songhua

    2016-04-01

    Cancer surveillance data are collected every year in the United States via the National Program of Cancer Registries (NPCR) and the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute (NCI). General trends are closely monitored to measure the nation’s progress against cancer. The objective of this study was to apply a novel web informatics approach for enabling fully automated monitoring of cancer mortality trends. The approach involves automated collection and text mining of online obituaries to derive the age distribution, geospatial, and temporal trends of cancer deaths in the US. Using breast and lung cancer asmore » examples, we mined 23,850 cancer-related and 413,024 general online obituaries spanning the timeframe 2008–2012. There was high correlation between the web-derived mortality trends and the official surveillance statistics reported by NCI with respect to the age distribution (ρ = 0.981 for breast; ρ = 0.994 for lung), the geospatial distribution (ρ = 0.939 for breast; ρ = 0.881 for lung), and the annual rates of cancer deaths (ρ = 0.661 for breast; ρ = 0.839 for lung). Additional experiments investigated the effect of sample size on the consistency of the web-based findings. Altogether, our study findings support web informatics as a promising, cost-effective way to dynamically monitor spatiotemporal cancer mortality trends.« less

  18. Metastasis-associated in colon cancer-1 in gastric cancer: Beyond metastasis

    PubMed Central

    Wu, Zhen-Zhen; Chen, Li-Shan; Zhou, Rui; Bin, Jian-Ping; Liao, Yu-Lin; Liao, Wang-Jun

    2016-01-01

    Metastasis-associated in colon cancer-1 (MACC1) is an oncogene that was first identified in colon cancer. The upstream and downstream of MACC1 form a delicate regulatory network that supports its tumorigenic role in cancers. Multiple functions of MACC1 have been discovered in many cancers. In gastric cancer (GC), MACC1 has been shown to be involved in oncogenesis and tumor progression. MACC1 overexpression adversely affects the clinical outcomes of GC patients. Regarding the mechanism of action of MACC1 in GC, studies have shown that it promotes the epithelial-to-mesenchymal transition and accelerates cancer metastasis. MACC1 is involved in many hallmarks of GC in addition to metastasis. MACC1 promotes vasculogenic mimicry (VM) via TWIST1/2, and VM increases the tumor blood supply, which is necessary for tumor progression. MACC1 also facilitates GC lymphangiogenesis by upregulating extracellular secretion of VEGF-C/D, indicating that MACC1 may be an important player in GC lymphatic dissemination. Additionally, MACC1 supports GC growth under metabolic stress by enhancing the Warburg effect. In conclusion, MACC1 participates in multiple biological processes inside and outside of GC cells, making it an important mediator of the tumor microenvironment. PMID:27547006

  19. Unique characteristics of adolescent and young adult acute lymphoblastic leukemia, breast cancer, and colon cancer.

    PubMed

    Tricoli, James V; Seibel, Nita L; Blair, Donald G; Albritton, Karen; Hayes-Lattin, Brandon

    2011-04-20

    Each year in the United States, nearly 70 000 individuals between the ages of 15 and 40 years are diagnosed with cancer. Although overall cancer survival rates among pediatric and older adult patients have increased in recent decades, there has been little improvement in survival of adolescent and young adult (AYA) cancer patients since 1975 when collected data became adequate to evaluate this issue. In 2006, the AYA Oncology Progress Review Group made recommendations for addressing the needs of this population that were later implemented by the LIVESTRONG Young Adult Alliance. One of their overriding questions was whether the cancers seen in AYA patients were biologically different than the same cancers in adult and/or pediatric patients. On June 9-10, 2009, the National Cancer Institute (NCI) and the Lance Armstrong Foundation (LAF) convened a workshop in Bethesda, MD, entitled "Unique Characteristics of AYA Cancers: Focus on Acute Lymphocytic Leukemia (ALL), Breast Cancer and Colon Cancer" that aimed to examine the current state of basic and translational research on these cancers and to discuss the next steps to improve their prognosis and treatment.

  20. Cancer of the colon and rectum: Potential effects of sex-age interactions on incidence and outcome

    PubMed Central

    Purim, Ofer; Gordon, Noa; Brenner, Baruch

    2013-01-01

    Background Sex differences in epidemiological, clinical and pathological characteristics of colorectal cancer have been under intensive investigation for the last three decades. Given that most of the sex-related differences reported were also age-related, this study sought to determine the potential effect of a sex-age interaction on colorectal cancer development and progression. Material/Methods Statistical data on sex- and age-specific colon or rectal cancer incidence, disease stage and survival for white persons were derived from the United States Surveillance, Epidemiology and End Results (SEER) Program. Age-specific incidence rates in 2002–2006 were analyzed by 5-year age groups (45–49, 50–54, 55–59, 60–64, 65–69, 70–74, 75–79, 80–84 years) in men and women. Sex differences were measured by calculating rate differences (RD) and rate ratios (RR). Equivalent analyses for a similar time period were performed for stage distribution and 5-year relative survival. Results Age-specific incidence rates were higher for men, for all life-time periods. However, the magnitude of the male predominance was age-dependent. The RR and RD did not remain constant over time: they increased gradually with age, peaked at 70–74 years, and declined thereafter. The distribution of stage at diagnosis was similar between men and women, but women seemed to have better survival, until the age of 64 years for colon cancer and 74 years for rectal cancer. Conclusions There seem to be significant age-related sex differences in the incidence of colorectal cancer, and maybe also in its prognosis. PMID:23511310

  1. Avenanthramides inhibit proliferation of human colon cancer cell lines in vitro

    Technology Transfer Automated Retrieval System (TEKTRAN)

    High intake of whole grain food is associated with reduced risk of colon cancer, but the mechanism underlying this protection has yet to be elucidated. Chronic inflammation and associated cyclooxygenase-2 (COX-2) expression in the colon epithelium are causally related to epithelial carcinogenesis, p...

  2. Autoantibodies to Ca2+ binding protein Calnuc is a potential marker in colon cancer detection.

    PubMed

    Chen, Yao; Lin, Ping; Qiu, Suimin; Peng, Xuan-Xian; Looi, Koksun; Farquhar, Marilyn Gist; Zhang, Jian-Ying

    2007-05-01

    Calnuc is a calcium (Ca2+) binding protein found in both Golgi and cytoplasm, and it may play a role in G protein- and Ca2+-regulated signal transduction events. This study was designed to investigate the possibility of whether Calnuc protein might be a tumor-associated antigen (TAA) that induces autoantibody response in human cancers, and to evaluate the feasibility of the Calnuc antigen-antibody system as a marker in cancer detection. Purified full-length recombinant Calnuc protein was used as an antigen in enzyme-linked immunoassay and Western blotting for the detection of autoantibodies in cancers. Sera from 447 patients with 9 different types of cancer were analyzed. Although the frequency of autoantibody to Calnuc was found to be 4.7% in total groups of cancer, it was not significantly different to that of normal individuals (1.2%). However, the frequency of autoantibody to Calnuc in colon cancer (11.5%) was significantly higher than that in normal individuals (1.2%). The expression analysis of Calnuc in multiple colon cancer tissues by immunohistochemistry on tissue array further confirmed the high specificity of Calnuc in colon cancer. Of 69 colon cancer tissue specimens examined, 41 tissues (59.4%) overexpressed Calnuc, while normal colon tissues did not show any expression of Calnuc. The subcellular distribution analysis of Calnuc examined by subcellular fractionation and immunofluorescence indicates that Calnuc is a membrane associated protein and mostly distributed in Golgi, which is consistent with previous reports. With adding Calnuc into a TAA array (including p53, c-myc, cyclin B1, cyclin D1), the cumulative frequency of antibody to multiple TAAs in colon cancer was raised to 65.4% which is significantly higher than the cumulative frequency in normal individuals (6.1%). This indicates that a mini-array of multiple TAAs which includes Calnuc might provide a novel non-invasive approach to enhance antibody detection for colon cancer diagnosis.

  3. Activation of ERK signaling and induction of colon cancer cell death by piperlongumine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Piperlongumine (PPLGM) is a bioactive compound isolated from long peppers that shows selective toxicity towards a variety of cancer cell types including colon cancer. The signaling pathways that lead to cancer cell death in response to PPLGM exposure have not been previously identified. Our objectiv...

  4. Histopathological identification of colon cancer with microsatellite instability.

    PubMed

    Alexander, J; Watanabe, T; Wu, T T; Rashid, A; Li, S; Hamilton, S R

    2001-02-01

    curve analysis, resulted in an odds ratio of 6.0 (P < 0.000001) with sensitivity of 75% and specificity of 67%. Our findings indicate that histopathological evaluation can be used to prioritize sporadic colon cancers for MSI studies, but morphological prediction of MSI-H has low sensitivity, requiring molecular analysis for therapeutic decisions.

  5. Polarization of macrophages in the tumor microenvironment is influenced by EGFR signaling within colon cancer cells

    PubMed Central

    Zhang, Weina; Chen, Lechuang; Ma, Kai; Zhao, Yahui; Liu, Xianghe; Wang, Yu; Liu, Mei; Liang, Shufang; Zhu, Hongxia; Xu, Ningzhi

    2016-01-01

    Epidermal growth factor receptor (EGFR) is a target of colon cancer therapy, but the effects of this therapy on the tumor microenvironment remain poorly understood. Our in vivo studies showed that cetuximab, an anti-EGFR monoclonal antibody, effectively inhibited AOM/DSS-induced, colitis-associated tumorigenesis, downregulated M2-related markers, and decreased F4/80+/CD206+ macrophage populations. Treatment with conditioned medium of colon cancer cells increased macrophage expression of the M2-related markers arginase-1 (Arg1), CCL17, CCL22, IL-10 and IL-4. By contrast, conditioned medium of EGFR knockout colon cancer cells inhibited expression of these M2-related markers and induced macrophage expression of the M1-related markers inducible nitric oxide synthase (iNOS), IL-12, TNF-α and CCR7. EGFR knockout in colon cancer cells inhibited macrophage-induced promotion of xenograft tumor growth. Moreover, colon cancer-derived insulin-like growth factor-1 (IGF-1) increased Arg1 expression, and treatment with the IGF1R inhibitor AG1024 inhibited that increase. These results suggest that inhibition of EGFR signaling in colon cancer cells modulates cytokine secretion (e.g. IGF-1) and prevents M1-to-M2 macrophage polarization, thereby inhibiting cancer cell growth. PMID:27683110

  6. Targeting the metabolic pathway of human colon cancer overcomes resistance to TRAIL-induced apoptosis.

    PubMed

    Carr, Ryan M; Qiao, Guilin; Qin, Jianzhong; Jayaraman, Sundararajan; Prabhakar, Bellur S; Maker, Ajay V

    2016-01-01

    Colon cancer is a leading cause of cancer-related mortality for which targeted therapy is needed; however, trials using apoptosis-inducing ligand monotherapy to overcome resistance to apoptosis have not shown clinical responses. Since colon cancer cells selectively uptake and rapidly metabolize glucose, a property utilized for clinical staging, we investigated mechanisms to alter glucose metabolism in order to selectively target the cancer cells and to overcome evasion of apoptosis. We demonstrate TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) resistance in the majority of human colon cancers tested and utilize the glucose analog 2-deoxy-d-glucose to sensitize TRAIL-resistant gastrointestinal adenocarcinoma cells, and not normal gastrointestinal epithelial cells, to TRAIL-induced apoptosis through enhanced death receptor 5 expression, downstream modulation of MAPK signaling and subsequent miRNA expression modulation by increasing the expression of miR-494 via MEK activation. Further, established human colon cancer xenografts treated with this strategy experience anti-tumor responses. These findings in colon adenocarcinoma support further investigation of manipulation of cellular energetics to selectively overcome resistance to apoptosis and to impart tumor regressions in established colon cancer tumors.

  7. Targeting the metabolic pathway of human colon cancer overcomes resistance to TRAIL-induced apoptosis

    PubMed Central

    Carr, Ryan M; Qiao, Guilin; Qin, Jianzhong; Jayaraman, Sundararajan; Prabhakar, Bellur S; Maker, Ajay V

    2016-01-01

    Colon cancer is a leading cause of cancer-related mortality for which targeted therapy is needed; however, trials using apoptosis-inducing ligand monotherapy to overcome resistance to apoptosis have not shown clinical responses. Since colon cancer cells selectively uptake and rapidly metabolize glucose, a property utilized for clinical staging, we investigated mechanisms to alter glucose metabolism in order to selectively target the cancer cells and to overcome evasion of apoptosis. We demonstrate TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) resistance in the majority of human colon cancers tested and utilize the glucose analog 2-deoxy-d-glucose to sensitize TRAIL-resistant gastrointestinal adenocarcinoma cells, and not normal gastrointestinal epithelial cells, to TRAIL-induced apoptosis through enhanced death receptor 5 expression, downstream modulation of MAPK signaling and subsequent miRNA expression modulation by increasing the expression of miR-494 via MEK activation. Further, established human colon cancer xenografts treated with this strategy experience anti-tumor responses. These findings in colon adenocarcinoma support further investigation of manipulation of cellular energetics to selectively overcome resistance to apoptosis and to impart tumor regressions in established colon cancer tumors. PMID:27648301

  8. Polarization of macrophages in the tumor microenvironment is influenced by EGFR signaling within colon cancer cells.

    PubMed

    Zhang, Weina; Chen, Lechuang; Ma, Kai; Zhao, Yahui; Liu, Xianghe; Wang, Yu; Liu, Mei; Liang, Shufang; Zhu, Hongxia; Xu, Ningzhi

    2016-11-15

    Epidermal growth factor receptor (EGFR) is a target of colon cancer therapy, but the effects of this therapy on the tumor microenvironment remain poorly understood. Our in vivo studies showed that cetuximab, an anti-EGFR monoclonal antibody, effectively inhibited AOM/DSS-induced, colitis-associated tumorigenesis, downregulated M2-related markers, and decreased F4/80+/CD206+ macrophage populations. Treatment with conditioned medium of colon cancer cells increased macrophage expression of the M2-related markers arginase-1 (Arg1), CCL17, CCL22, IL-10 and IL-4. By contrast, conditioned medium of EGFR knockout colon cancer cells inhibited expression of these M2-related markers and induced macrophage expression of the M1-related markers inducible nitric oxide synthase (iNOS), IL-12, TNF-α and CCR7. EGFR knockout in colon cancer cells inhibited macrophage-induced promotion of xenograft tumor growth. Moreover, colon cancer-derived insulin-like growth factor-1 (IGF-1) increased Arg1 expression, and treatment with the IGF1R inhibitor AG1024 inhibited that increase. These results suggest that inhibition of EGFR signaling in colon cancer cells modulates cytokine secretion (e.g. IGF-1) and prevents M1-to-M2 macrophage polarization, thereby inhibiting cancer cell growth.

  9. Innate lymphoid cells sustain colon cancer through production of interleukin-22 in a mouse model.

    PubMed

    Kirchberger, Stefanie; Royston, Daniel J; Boulard, Olivier; Thornton, Emily; Franchini, Fanny; Szabady, Rose L; Harrison, Oliver; Powrie, Fiona

    2013-05-06

    Patients with inflammatory bowel disease (IBD) have an increased risk of colon cancer. However, the immune cells and cytokines that mediate the transition from intestinal inflammation to cancer are poorly understood. We show that bacteria-induced colon cancer is accompanied by differential accumulation of IL-17(+)IL-22(+) colonic innate lymphoid cells (cILCs), which are phenotypically distinct from LTi and NK-22 cells, and that their depletion in mice with dysplastic inflammation blocks the development of invasive colon cancer. Analysis of the functional role of distinct Type 17 cytokines shows that although blockade of IL-17 inhibits some parameters of intestinal inflammation, reduction in dysplasia and colorectal cancer (CRC) requires neutralization of IL-22 indicating a unique role for IL-22 in the maintenance of cancer in this model. Mechanistic analyses showed that IL-22 selectively acts on epithelial cells to induce Stat3 phosphorylation and proliferation. Importantly, we could detect IL-22(+)CD3(+) and IL-22(+)CD3(−) cells in human CRC. Our results describe a new activity of IL-22 in the colon as a nonredundant mediator of the inflammatory cascade required for perpetuation of CRC, highlighting the IL-22 axis as a novel therapeutic target in colon cancer.

  10. Surveillance of patients with chronic ulcerative colitis. WHO Collaborating Centre for the Prevention of Colorectal Cancer.

    PubMed Central

    Levin, B.; Lennard-Jones, J.; Riddell, R. H.; Sachar, D.; Winawer, S. J.

    1991-01-01

    In chronic ulcerative colitis, the object of surveillance is prevention of cancer or at least prevention of death from cancer by diagnosis at an early curable stage or by detection at a pre-malignant phase. Patients must be informed about their cancer risk as well as the limitations of endoscopic surveillance and the availability of surgical alternatives. Physicians must bear in mind the risks, benefits and costs of surveillance procedures. Patients at greatest risk of cancer for whom endoscopic surveillance is warranted are those with extensive colitis of greater than 8 years duration. Colonoscopy should be performed every 1 to 2 years at which time multiple biopsies are obtained from every 10-12 cm of normal-appearing mucosa. Targeted biopsies should also be obtained from areas where the surface appears raised as a broad-based polyp, low irregular plaque or villiform elevation, or from an unusual ulcer, particularly one with raised edges, or from a stricture. Typical inflammatory polyps need not be sampled. Colectomy is recommended in the presence of multifocal high-grade dysplasia if confirmed by an experienced pathologist. The identification of a mass lesion associated with any degree of overlying dysplasia is also a generally accepted indication for colectomy, while persistent low-grade dysplasia without a mass is somewhat more controversial. Recently introduced biomarkers may replace or supplement dysplasia in surveillance programmes as well as provide new information about malignant transformation. PMID:1905205

  11. Affinity-based strategies to fast track development of colon cancer biomarkers — EDRN Public Portal

    Cancer.gov

    Our goal is to discover plasma and tissue-based tumor biomarkers that work well enough together to identity colon cancer at early stages, lead to accurate diagnosis and could ultimately allow for individualized treatment.

  12. How MicroRNAs Influence both Hereditary and Inflammatory-mediated Colon Cancer

    PubMed Central

    Hutchison, Jennifer; Cohen, Zoe; Onyeaguchi, Benjamin C.; Funk, Janet; Nelson, Mark A.

    2013-01-01

    MicroRNAs have emerged as important post-translational regulators of gene expression and are involved in several physiological and pathological states including the pathogenesis of human colon cancers. In regards to tumor development, microRNAs can act as oncogenes or tumor suppressors. Both hereditary predispositions (i.e. Lynch Syndrome and Familial Adenomatous Polyposis) contribute to the development of colon cancer. In addition, individuals who suffer from inflammatory bowel diseases such as Crohn’s disease or ulcerative colitis have a higher risk of developing colon cancer. Here, we discuss the occurrence of the deregulated expression of miRNAs in colon cancer that arise due to hereditary predisposition and inflammatory bowel disease. PMID:24042167

  13. Special Section: New Ways to Detect Colon Cancer 3-D virtual screening now being used

    MedlinePlus

    ... New Ways to Detect Colon Cancer 3-D virtual screening now being used Past Issues / Spring 2009 ... showcases a 3-D image generated by the virtual colonoscopy software he invented with a team of ...

  14. Metastatic colon cancer from extrahepatic cholangiocarcinoma presenting as painless jaundice: case report and literature review.

    PubMed

    Vabi, Benjamin W; Carter, Jeffrey; Rong, Rong; Wang, Minhua; Corasanti, James G; Gibbs, John F

    2016-04-01

    Cholangiocarcinoma (CCA) is a rare cancer of the biliary epithelium comprising only about 3% of all gastrointestinal malignancies. It is a highly aggressive malignancy and confers a dismal prognosis with majority of patients presenting with metastatic disease. Metastatic CCA to the colon is extremely rare with only few cases reported in the literature. We present a 61-year-old patient with incidental synchronous metastatic colonic adenocarcinoma from extra-hepatic CCA. Laboratory data revealed significant indirect hyperbilirubinemia and transaminitis. Imaging study showed intrahepatic bile ducts prominence without mass lesions. Incidentally, there was diffuse colonic thickening without mass lesions or obstruction. Endoscopic retrograde cholangiopancreatography (ERCP) showed a common bile duct stricture. Brushings were consistent with CCA. Screening colonoscopy identified nodularity and biopsy and immunostaining were consistent with CCA metastasis to colon. The patient elected for palliative and comfort care. Metastatic CCA to the colon is a rare pattern of distant spread that may pose a diagnostic challenge. Some salient characteristics may assist in the differentiation of primary colon cancer and metastatic colon cancer from CCA. Little remains known about the pathogenic behavior of metastatic secondary colorectal cancer. And more so, the management approach to such metastatic cancer still remains to be defined. Screening colonoscopy in patients presenting with resectable CCA may alter management. Furthermore, whether patients with history of resected CCA may benefit from a more frequent screening colonoscopy remains to be validated.

  15. The Sirtuin 3 Expression Profile Is Associated with Pathological and Clinical Outcomes in Colon Cancer Patients

    PubMed Central

    Liu, Chunyuan; Huang, Zonghai; Jiang, Hong; Shi, Fujun

    2014-01-01

    Aim. To investigate the correlation between Sirtuin 3 (SIRT3) expression and the clinical outcome of patients with colon cancer. Methods. The tumor specimens from 127 patients with colon cancer were obtained for SIRT3 immunohistochemical staining. Patients were followed up. In in vitro study, SIRT3 gene was inhibited to observe the effects of SIRT3 on the biological behavior of cultured colon cells. Results. The SIRT3 expression level was found to be significantly associated with the lymph node metastasis (P < 0.001) and tumor stages (P < 0.001). The colon cancer-specific survival was 64.6% among patients with high SIRT3 expressions and 88.6% among patients with low SIRT3 expressions (log-rank P = 0.016). The overall survival was 80.2% among patients with low SIRT3 expressions and 55.9% among patients with high SIRT3 expressions (log-rank P = 0.002). In vitro study showed that silencing of SIRT3 gene inhibited the proliferation, invasion, and cells migration but increased the apoptosis in the cultured colon cell lines. Conclusion. This study provides evidence supporting that SIRT3 is closely associated with the clinical outcomes of colon cancer. SIRT3 may be considered as a marker for colon cancer. PMID:25105144

  16. Prospective multicenter study of the impact of oncotype DX colon cancer assay results on treatment recommendations in stage II colon cancer patients.

    PubMed

    Srivastava, Geetika; Renfro, Lindsay A; Behrens, Robert J; Lopatin, Margarita; Chao, Calvin; Soori, Gamini S; Dakhil, Shaker R; Mowat, Rex B; Kuebler, J Philip; Kim, George; Mazurczak, Miroslaw; Lee, Mark; Alberts, Steven R

    2014-05-01

    The Oncotype DX colon cancer assay is a clinically validated predictor of recurrence risk in stage II colon cancer patients. This prospective study evaluated the impact of recurrence score (RS) results on physician recommendations regarding adjuvant chemotherapy in T3, mismatch repair-proficient (MMR-P) stage II colon cancer patients. Patients and Methods. Stage IIA colon cancer patients were enrolled in 17 centers. Patient tumor specimens were assessed by the RS test (quantitative reverse transcription-polymerase chain reaction) and mismatch repair (immunohistochemistry). For each patient, the physician's recommended postoperative treatment plan of observation, fluoropyrimidine monotherapy, or combination therapy with oxaliplatin was recorded before and after the RS and mismatch repair results were provided. Results. Of 221 enrolled patients, 141 patients had T3 MMR-P tumors and were eligible for the primary analysis. Treatment recommendations changed for 63 (45%; 95% confidence interval: 36%-53%) of these 141 T3 MMR-P patients, with intensity decreasing for 47 (33%) and increasing for 16 (11%). Recommendations for chemotherapy decreased from 73 patients (52%) to 42 (30%), following review of RS results by physician and patient. Increased treatment intensity was more often observed at higher RS values, and decreased intensity was observed at lower values (p = .011). Conclusion. Compared with traditional clinicopathological assessment, incorporation of the RS result into clinical decision making was associated with treatment recommendation changes for 45% of T3 MMR-P stage II colon cancer patients in this prospective multicenter study. Use of the RS assay may lead to overall reduction in adjuvant chemotherapy use in this subgroup of stage II colon cancer patients.

  17. Prospective Multicenter Study of the Impact of Oncotype DX Colon Cancer Assay Results on Treatment Recommendations in Stage II Colon Cancer Patients

    PubMed Central

    Srivastava, Geetika; Renfro, Lindsay A.; Behrens, Robert J.; Lopatin, Margarita; Chao, Calvin; Soori, Gamini S.; Dakhil, Shaker R.; Mowat, Rex B.; Kuebler, J. Philip; Kim, George; Mazurczak, Miroslaw; Lee, Mark

    2014-01-01

    Purpose. The Oncotype DX colon cancer assay is a clinically validated predictor of recurrence risk in stage II colon cancer patients. This prospective study evaluated the impact of recurrence score (RS) results on physician recommendations regarding adjuvant chemotherapy in T3, mismatch repair-proficient (MMR-P) stage II colon cancer patients. Patients and Methods. Stage IIA colon cancer patients were enrolled in 17 centers. Patient tumor specimens were assessed by the RS test (quantitative reverse transcription-polymerase chain reaction) and mismatch repair (immunohistochemistry). For each patient, the physician’s recommended postoperative treatment plan of observation, fluoropyrimidine monotherapy, or combination therapy with oxaliplatin was recorded before and after the RS and mismatch repair results were provided. Results. Of 221 enrolled patients, 141 patients had T3 MMR-P tumors and were eligible for the primary analysis. Treatment recommendations changed for 63 (45%; 95% confidence interval: 36%–53%) of these 141 T3 MMR-P patients, with intensity decreasing for 47 (33%) and increasing for 16 (11%). Recommendations for chemotherapy decreased from 73 patients (52%) to 42 (30%), following review of RS results by physician and patient. Increased treatment intensity was more often observed at higher RS values, and decreased intensity was observed at lower values (p = .011). Conclusion. Compared with traditional clinicopathological assessment, incorporation of the RS result into clinical decision making was associated with treatment recommendation changes for 45% of T3 MMR-P stage II colon cancer patients in this prospective multicenter study. Use of the RS assay may lead to overall reduction in adjuvant chemotherapy use in this subgroup of stage II colon cancer patients. PMID:24710310

  18. Red meat and colon cancer: dietary haem-induced colonic cytotoxicity and epithelial hyperproliferation are inhibited by calcium.

    PubMed

    Sesink, A L; Termont, D S; Kleibeuker, J H; Van der Meer, R

    2001-10-01

    High intake of red meat is associated with increased colon cancer risk. We have shown earlier that this may be due to the high haem content of red meat, because dietary haem increased cytolytic activity of faecal water and colonic epithelial proliferation. Dietary calcium inhibits diet-induced epithelial hyperproliferation. Furthermore, it has been shown that supplemental calcium inhibited the recurrence of colorectal adenomas. Therefore, we studied whether dietary calcium phosphate can exert its protective effects by inhibiting the deleterious effects of haem. In vitro, calcium phosphate precipitated haem and inhibited the haem-induced cytotoxicity. Subsequently, rats were fed diets, differing in haem (0 or 1.3 micromol/g) and calcium phosphate content only (20 or 180 micromol/g). Faeces were collected for biochemical analyses. Cytolytic activity of faecal water was determined from the degree of lysis of erythrocytes by faecal water. Colonic epithelial proliferation was measured in vivo using [(3)H]thymidine incorporation. In rats fed low calcium diets, dietary haem increased cytolytic activity of faecal water (98 +/- 1 versus 1 +/- 1%, P < 0.001) and the concentration of cations in faeces (964 +/- 31 versus 254 +/- 20 micromol/g), when compared with controls. This indicates that dietary haem increased colonic mucosal exposure to luminal irritants. Colonic epithelial proliferation was increased compared with controls (70 +/- 4 versus 48 +/- 8 d.p.m./microg DNA, P < 0.001). This was accompanied by metabolism of the ingested haem and solubilization of haem compounds in the faecal water. A high calcium diet largely prevented this metabolism and solubilization. It also inhibited the haem-induced cytolytic activity of faecal water and increase in faecal cation concentration. In accordance, the haem-induced colonic epithelial hyperproliferation was prevented. We therefore suggest that dietary calcium phosphate acts as a chemopreventive agent in colon carcinogenesis by

  19. Helicobacter Infection Is Required for Inflammation and Colon Cancer in Smad3-Deficient Mice

    PubMed Central

    Maggio-Price, Lillian; Treuting, Piper; Zeng, Weiping; Tsang, Mark; Bielefeldt-Ohmann, Helle; Iritani, Brian M.

    2017-01-01

    Accumulating evidence suggests that intestinal microbial organisms may play an important role in triggering and sustaining inflammation in individuals afflicted with inflammatory bowel disease (IBD). Moreover, individuals with IBD are at increased risk for developing colorectal cancer, suggesting that chronic inflammation may initiate genetic or epigenetic changes associated with cancer development. We tested the hypothesis that bacteria may contribute to the development of colon cancer by synergizing with defective transforming growth factor-β (TGF-β) signaling, a pathway commonly mutated in human colon cancer. Although others have reported that mice deficient in the TGF-β signaling molecule SMAD3 develop colon cancer, we found that SMAD3-deficient mice maintained free of the Gram-negative enterohepatic bacteria Helicobacter spp. for up to 9 months do not develop colon cancer. Furthermore, infection of SMAD3−/− mice with Helicobacter triggers colon cancer in 50% to 66% of the animals. Using real-time PCR, we found that Helicobacter organisms concentrate in the cecum, the preferred site of tumor development. Mucinous adenocarcinomas develop 5 to 30 weeks after infection and are preceded by an early inflammatory phase, consisting of increased proliferation of epithelial cells; increased numbers of cyclooxygenase-2–positive cells, CD4+ T cells, macrophages; and increased MHC class II expression. Colonic tissue revealed increased transcripts for the oncogene c-myc and the proinflammatory cytokines interleukin-1α (IL-1α), IL-1β, IL-6, IFN-γ, and tumor necrosis factor-α, some of which have been implicated in colon cancer. These results suggest that bacteria may be important in triggering colorectal cancer, notably in the context of gene mutations in the TGF-β signaling pathway, one of the most commonly affected cellular pathways in colorectal cancer in humans. PMID:16424015

  20. Colon cancer treatment: Are there racial disparities in an equal-access healthcare system?

    PubMed Central

    Gill, Abegail A.; Enewold, Lindsey; Zahm, Shelia H.; Shriver, Craig D.; Stojadinovic, Alexander; McGlynn, Katherine A.; Zhu, Kangmin

    2014-01-01

    Background In the general US population, blacks and whites have been shown to undergo colon cancer treatment at disproportionate rates. Accessibility to medical care may be the most important factor influencing differences in colon cancer treatment among whites and blacks. Objective This study assessed whether racial disparities in colon cancer surgery and chemotherapy existed in an equal-access healthcare system. Additionally, we sought to examine whether racial differences varied by demographic and tumor characteristics. Design and Setting Database research using the United States Department of Defense’s (DoD) Military Health System. Patients Patients included 2,560 Non-Hispanic Whites (NHW) and Non-Hispanic Blacks (NHB) with colon cancer diagnosed from 1998 to 2007. Main Outcome Measures Logistic regression was used to assess the associations between race and the receipt of colon cancer surgery or chemotherapy, while controlling for available potential confounders, both overall and stratified by age at diagnosis, sex, and tumor stage. Results After multivariate adjustment, the odds of receiving colon cancer surgery or chemotherapy NHBs versus NHWs were similar (OR: 0.75, 95% CI: 0.37–1.53; OR: 0.79, 95% CI: 0.59–1.04; respectively). Additionally, no effect modification by age at diagnosis, sex, and tumor stage were observed. Limitations Treatment data might not be complete for beneficiaries who also had non-DoD health insurance. Conclusions When access to medical care is equal, racial disparities in the provision of colon cancer surgery and chemotherapy were not apparent. Thus, it is possible that the inequalities in access to care play a major role in the racial disparities seen in colon cancer treatment in the general population. PMID:25101601

  1. A cancer-favoring oncolytic vaccinia virus shows enhanced suppression of stem-cell like colon cancer

    PubMed Central

    Yoo, So Young; Bang, Seo Young; Jeong, Su-Nam; Kang, Dae Hwan; Heo, Jeong

    2016-01-01

    Stem cell-like colon cancer cells (SCCs) pose a major challenge in colon cancer treatment because of their resistance to chemotherapy and radiotherapy. Oncolytic virus-based therapy has shown promising results in uncured cancer patients; however, its effects on SCCs are not well studied yet. Here, we engineered a cancer-favoring oncolytic vaccinia virus (CVV) as a potent biotherapeutic and investigated its therapeutic efficacy in terms of killing SCCs. CVV is an evolved Wyeth strain vaccinia virus (EVV) lacking the viral thymidine kinase. SCC models were established using human or mouse colon cancer spheres, which continuously expressed stemness markers. The cancer-favoring characteristics and different cytotoxic pathways for killing cancer cells successfully overrode general drug resistance, thereby killing colon cancer cells regardless of the presence of SCCs. Subcutaneously injected HT29 spheres showed lower growth in CVV-treated models than in 5-Fu-treated models. Intraperitoneally injected CT26 spheres induced tumor masses in the abdominal region. CVV-treated groups showed higher survival rates and smaller tumor mass formation, compared to 5-Fu-treated groups. Interestingly, the combined treatment of CVV with 5-Fu showed improved survival rates and complete suppression of tumor mass. The CVV developed in this study, thus, effectively suppresses SCCs, which can be synergistically enhanced by simultaneous treatment with the anticancer drug 5-Fu. Our novel CVV is highly advantageous as a next-generation therapeutic for treating colon cancer. PMID:26918725

  2. Association of [-2]proPSA with Biopsy Reclassification During Active Surveillance for Prostate Cancer

    PubMed Central

    Tosoian, Jeffrey J.; Loeb, Stacy; Feng, Zhaoyong; Isharwal, Sumit; Landis, Patricia; Elliot, Debra J.; Veltri, Robert; Epstein, Jonathan I.; Partin, Alan W.; Carter, H. Ballentine; Trock, Bruce; Sokoll, Lori J.

    2014-01-01

    Purpose Previous studies have suggested an association between [-2]proPSA expression and prostate cancer detection. Less is known about the utility of this marker in following prostate cancer patients on active surveillance. Thus, our objective was to examine the relationship between [-2]proPSA and biopsy results in men enrolled in an active surveillance program. Materials and Methods In 167 men from our institutional active surveillance program, we used Cox proportional hazards models to examine the relationship between [-2]proPSA and annual surveillance biopsy results. The outcome of interest was biopsy reclassification (Gleason score ≥7, or >2 positive biopsy cores, or >50% involvement of any core with cancer). We also examined the association of biopsy results with total PSA, %fPSA, [-2]proPSA/%fPSA, and the Beckman Coulter Prostate Health Index [phi=([-2]proPSA/fPSA) x (tPSA)½]. Results While on active surveillance (median time from diagnosis 4.3 years), 63 (37.7%) men demonstrated biopsy reclassification based on the above criteria, including 28 (16.7%) of whom had reclassification based on Gleason score upgrading (Gleason score≥7). Baseline and longitudinal %fPSA, %[-2]proPSA, [-2]proPSA/%fPSA, and phi measurements were significantly associated with biopsy reclassification, and %[-2]proPSA and phi provided the greatest predictive accuracy for high-grade cancer. Conclusions In men on active surveillance, measures based on [-2]proPSA such as phi, appear to provide improved prediction of biopsy reclassification during follow-up. Additional validation is warranted to determine whether clinically useful thresholds can be defined, and to better characterize the role of %[-2]proPSA and phi in conjunction with other markers in monitoring patients enrolled in active surveillance. PMID:22901577

  3. Prior colonization is associated with increased risk of antibiotic-resistant Gram-negative bacteremia in cancer patients☆,☆☆

    PubMed Central

    Kleinberg, Michael; Sorkin, John D.; Netzer, Giora; Johnson, Jennifer K.; Shardell, Michelle; Thom, Kerri A.; Harris, Anthony D.; Roghmann, Mary-Claire

    2015-01-01

    We hypothesized that prior colonization with antibiotic-resistant Gram-negative bacteria is associated with increased risk of subsequent antibiotic-resistant Gram-negative bacteremia among cancer patients. We performed a matched case-control study. Cases were cancer patients with a blood culture positive for antibiotic-resistant Gram-negative bacteria. Controls were cancer patients with a blood culture not positive for antibiotic-resistant Gram-negative bacteria. Prior colonization was defined as any antibiotic-resistant Gram-negative bacteria in surveillance or non-sterile-site cultures obtained 2–365 days before the bacteremia. Thirty-two (37%) of 86 cases and 27 (8%) of 323 matched controls were previously colonized by any antibiotic-resistant Gram-negative bacteria. Prior colonization was strongly associated with antibiotic-resistant Gram-negative bacteremia (odds ratio [OR] 7.2, 95% confidence interval [CI] 3.5–14.7) after controlling for recent treatment with piperacillin-tazobactam (OR 2.5, 95% CI 1.3–4.8). In these patients with suspected bacteremia, prior cultures may predict increased risk of antibiotic-resistant Gram-negative bacteremia. PMID:24582582

  4. The utility of Apc-mutant rats in modeling human colon cancer

    PubMed Central

    Irving, Amy A.; Yoshimi, Kazuto; Hart, Marcia L.; Parker, Taybor; Clipson, Linda; Ford, Madeline R.; Kuramoto, Takashi; Dove, William F.; Amos-Landgraf, James M.

    2014-01-01

    Prior to the advent of genetic engineering in the mouse, the rat was the model of choice for investigating the etiology of cancer. Now, recent advances in the manipulation of the rat genome, combined with a growing recognition of the physiological differences between mice and rats, have reignited interest in the rat as a model of human cancer. Two recently developed rat models, the polyposis in the rat colon (Pirc) and Kyoto Apc Delta (KAD) strains, each carry mutations in the intestinal-cancer-associated adenomatous polyposis coli (Apc) gene. In contrast to mouse models carrying Apc mutations, in which cancers develop mainly in the small intestine rather than in the colon and there is no gender bias, these rat models exhibit colonic predisposition and gender-specific susceptibility, as seen in human colon cancer. The rat also provides other experimental resources as a model organism that are not provided by the mouse: the structure of its chromosomes facilitates the analysis of genomic events, the size of its colon permits longitudinal analysis of tumor growth, and the size of biological samples from the animal facilitates multiplexed molecular analyses of the tumor and its host. Thus, the underlying biology and experimental resources of these rat models provide important avenues for investigation. We anticipate that advances in disease modeling in the rat will synergize with resources that are being developed in the mouse to provide a deeper understanding of human colon cancer. PMID:25288683

  5. INPP4B is an oncogenic regulator in human colon cancer

    PubMed Central

    Guo, S T; Chi, M N; Yang, R H; Guo, X Y; Zan, L K; Wang, C Y; Xi, Y F; Jin, L; Croft, A; Tseng, H-Y; Yan, X G; Farrelly, M; Wang, F H; Lai, F; Wang, J F; Li, Y P; Ackland, S; Scott, R; Agoulnik, I U; Hondermarck, H; Thorne, R F; Liu, T; Zhang, X D; Jiang, C C

    2016-01-01

    Inositol polyphosphate 4-phosphatase type II (INPP4B) negatively regulates phosphatidylinositol 3-kinase signaling and is a tumor suppressor in some types of cancers. However, we have found that it is frequently upregulated in human colon cancer cells. Here we show that silencing of INPP4B blocks activation of Akt and serum- and glucocorticoid-regulated kinase 3 (SGK3), inhibits colon cancer cell proliferation and retards colon cancer xenograft growth. Conversely, overexpression of INPP4B increases proliferation and triggers anchorage-independent growth of normal colon epithelial cells. Moreover, we demonstrate that the effect of INPP4B on Akt and SGK3 is associated with inactivation of phosphate and tensin homolog through its protein phosphatase activity and that the increase in INPP4B is due to Ets-1-mediated transcriptional upregulation in colon cancer cells. Collectively, these results suggest that INPP4B may function as an oncogenic driver in colon cancer, with potential implications for targeting INPP4B as a novel approach to treat this disease. PMID:26411369

  6. The utility of Apc-mutant rats in modeling human colon cancer.

    PubMed

    Irving, Amy A; Yoshimi, Kazuto; Hart, Marcia L; Parker, Taybor; Clipson, Linda; Ford, Madeline R; Kuramoto, Takashi; Dove, William F; Amos-Landgraf, James M

    2014-11-01

    Prior to the advent of genetic engineering in the mouse, the rat was the model of choice for investigating the etiology of cancer. Now, recent advances in the manipulation of the rat genome, combined with a growing recognition of the physiological differences between mice and rats, have reignited interest in the rat as a model of human cancer. Two recently developed rat models, the polyposis in the rat colon (Pirc) and Kyoto Apc Delta (KAD) strains, each carry mutations in the intestinal-cancer-associated adenomatous polyposis coli (Apc) gene. In contrast to mouse models carrying Apc mutations, in which cancers develop mainly in the small intestine rather than in the colon and there is no gender bias, these rat models exhibit colonic predisposition and gender-specific susceptibility, as seen in human colon cancer. The rat also provides other experimental resources as a model organism that are not provided by the mouse: the structure of its chromosomes facilitates the analysis of genomic events, the size of its colon permits longitudinal analysis of tumor growth, and the size of biological samples from the animal facilitates multiplexed molecular analyses of the tumor and its host. Thus, the underlying biology and experimental resources of these rat models provide important avenues for investigation. We anticipate that advances in disease modeling in the rat will synergize with resources that are being developed in the mouse to provide a deeper understanding of human colon cancer.

  7. Phosphatase PRL-3 is a direct regulatory target of TGFbeta in colon cancer metastasis.

    PubMed

    Jiang, Yanjun; Liu, Xiao-Qiong; Rajput, Ashwani; Geng, Liying; Ongchin, Melanie; Zeng, Qi; Taylor, Gregory S; Wang, Jing

    2011-01-01

    Metastasis causes most deaths from cancer yet mechanistic understanding and therapeutic options remain limited. Overexpression of the phosphatase PRL-3 (phosphatase of regenerating liver) is associated with metastasis of colon cancer. Here, we show that PRL-3 is a direct target of signaling by TGFβ, which is broadly implicated in progression and metastasis. We found that suppression of PRL-3 expression by TGFβ was mediated by Smad-dependent inhibition of PRL-3 transcription at the level of promoter activity. PRL-3 activation stimulated PI3K/AKT signaling that caused resistance to stress-induced apoptosis. PRL-3 overexpression promoted metastatic colonization in an orthotopic mouse model of colon cancer, whereas PRL-3 knockdown reduced metastatic potential. Altered metastatic phenotypes were not derivative of primary tumor development or local invasion but could be attributed to PRL-3-mediated cell survival. Our findings suggest that inhibiting PRL-3 expression might be an important mechanism through which TGFβ suppresses metastasis in colon cancer. In addition, our findings suggest that loss of TGFβ signaling, which occurs commonly during colon cancer progression, is sufficient to activate a PRL-3-mediated cell survival pathway that can selectively promote metastasis. Therefore, a major implication of our findings is that PRL-3 antagonists may offer significant value for antimetastatic therapy in patients with colon cancer.

  8. Lack of functioning intratumoral lymphatics in colon and pancreas cancer tissue.

    PubMed

    Olszewski, Waldemar L; Stanczyk, Marek; Gewartowska, Magdalena; Domaszewska-Szostek, Anna; Durlik, Marek

    2012-09-01

    There are controversial views as to whether intratumoral or peritumoral lymphatics play a dominant role in the metastatic process. Most clinical observations originate from studies of colon cancer. Colon contains mucosa and submucosa rich in lymphatics and with high lymph formation rate. This seems to be a prerequisite for easy metastasis of cancer cells to regional lymph nodes. However, there are other tissues as pancreas with a rudimentary lymphatic network where cancer metastasis formation is as intensive as in colon cancer. This contradicts the common notion that intratumor lymphatics play major role in metastases. We visualized interstitial space and lymphatics in the central and peripheral regions of colon and pancreas tumors using the color stereoscopic lymphography and simultaneously immunohistochemical performed stainings specific for lymphatic and blood endothelial cells. The density of open and compressed lymphatic and blood vessels was measured in the tumor core and edge. There were very few lymphatics in the colon and pancreas tumor core but numerous minor fluid "lakes" with no visible connection to the peritumoral lymphatics. Lining of "lakes" did not express molecular markers specific for lymphatic endothelial cells. Dense connective tissue surrounding tumor foci did not contain lymphatics. Peritumoral lymphatics were irregularly distributed in both types of tumor and only sporadically contained cells that might be tumor cells. Similar lymphoscintigraphic and histological pictures were seen in colon and pancreas cancer despite of different structure of both tissues. This suggests a uniform reaction of tissues to the growing cancer irrespective of the affected organ.

  9. Dehydropeptidase 1 promotes metastasis through regulation of E-cadherin expression in colon cancer

    PubMed Central

    Park, Sang Yoon; Lee, Seon-Jin; Cho, Hee Jun; Kim, Tae Woo; Kim, Jong-Tae; Kim, Jae Wha; Lee, Chul-Ho; Kim, Bo-Yeon; Yeom, Young Il; Lim, Jong-Seok; Lee, Younghee; Lee, Hee Gu

    2016-01-01

    Dehydropeptidase 1 (DPEP1) is a zinc-dependent metalloproteinase that is expressed aberrantly in several cancers. The role of DPEP1 in cancer remain controversial. In this study, we demonstrate that DPEP1 functions as a positive regulator for colon cancer cell metastasis. The expression of DPEP1 mRNA and proteins were upregulated in colon cancer tissues compared to normal mucosa. Gain-of-function and loss-of-function approaches were used to examine the malignant phenotype of DPEP1-expressing or DPEP1-depleted cells. DPEP1 expression caused a significant increase in colon cancer cell adhesion and invasion in vitro, and metastasis in vivo. In contrast, DPEP1 depletion induced opposite effects. Furthermore, cilastatin, a DPEP1 inhibitor, suppressed the invasion and metastasis of DPEP1-expressing cells. DPEP1 inhibited the leukotriene D4 signaling pathway and increased the expression of E-cadherin. We also show that DPEP1 mediates TGF-β-induced EMT. TGF-β transcriptionally repressed DPEP1 expression. TGF-β treatment decreased E-cadherin expression and promoted cell invasion in DPEP1-expressing colon cancer cell lines, whereas it did not affect these parameters in DPEP1-depleted cell lines. These results suggest that DPEP1 promotes cancer metastasis by regulating E-cadherin plasticity and that it might be a potential therapeutic target for preventing the progression of colon cancer. PMID:26824987

  10. Circulating DNA and its methylation level in inflammatory bowel disease and related colon cancer.

    PubMed

    Bai, Xuming; Zhu, Yaqun; Pu, Wangyang; Xiao, Li; Li, Kai; Xing, Chungen; Jin, Yong

    2015-01-01

    Both of chronic inflammation and abnormal immune in inflammatory bowel disease can induce colon cancer. Previous research showed that cell apoptosis and necrosis become the main source of circulating DNA in the peripheral blood during tumorigenesis that reduced along with methylation degree. However, its role in the process of colitis transforming to colon cancer is not clarified. Drinking 3% DSS was used to establish colitis model, while 3% dextran sodium sulfate (DSS) combined with azo oxidation methane (AOM) intraperitoneal injection was applied to establish colitis related colon cancer model. Circulating DNA and its methylation level in peripheral blood were tested. Morphology observation, HE staining, and p53 and β-catenin expression detection confirmed that drinking 3% DSS and 3% DSS combined with AOM intraperitoneal injection can successfully establish colitis and colitis associated colorectal cancer models. Circulating DNA level in colitis and colon cancer mice increased by gradient compared with control, while significant difference was observed between each other. Circulating DNA methylation level decreased obviously in colitis and colon cancer, and significant difference was observed between each other. Abnormal protein expression, circulating DNA and its methylation level in ulcerative colitis associated colorectal tissues change in gradient, suggesting that circulating DNA and its methylation level can be treated as new markers for colitis cancer transformation that has certain significance to explore the mechanism of human ulcerative colitis canceration.

  11. Transcriptomic molecular markers for screening human colon cancer in stool and tissue.

    PubMed

    Ahmed, Farid E; Vos, Paul; iJames, Stephanie; Lysle, Donald T; Allison, Ron R; Flake, Gordon; Sinar, Dennis R; Naziri, Wade; Marcuard, Stefan P; Pennington, Rodney

    2007-01-01

    There is a need for sensitive and specific diagnostic molecular markers that can be used to monitor early patterns of gene expression in non-invasive exfoliated colonocytes shed in the stool, and in situ in adenoma-carcinoma epithelium of the colon. RNA-based detection methods are more comprehensive than either DNA-, protein- or methylation-based screening methods. By routinely and systematically being able to perform quantitative gene expression studies on these samples using less than ten colon cancer genes selected by the enormous resources of the National Cancer Institute's Cancer Genome Anatomy Project, we were able to monitor changes at various stages in the neoplastic process, allowing for reliable diagnostic screening of colon cancer particularly at the early, pre-malignant stages. Although the expression of some of the genes tested in tissue showed less variability in normal or cancerous patients than in stool, the stool by itself is suitable for screening. Thus, a transcriptomic approach using stool or tissue samples promises to offer more sensitivity and specificity than currently used molecular screening methods for colon cancer. A larger prospective clinical study utilizing stool and tissue samples derived from many control and colon cancer patients, to allow for a statistically valid analysis, is now urgently required to determine the true sensitivity and specificity of the transcriptomic screening approach for this preventable cancer.

  12. ColonCancerCheck Primary Care Invitation Pilot project

    PubMed Central

    Tinmouth, Jill; Ritvo, Paul; McGregor, S. Elizabeth; Patel, Jigisha; Guglietti, Crissa; Levitt, Cheryl A.; Paszat, Lawrence F.; Rabeneck, Linda

    2013-01-01

    Abstract Objective To describe the perceptions of those who received invitations to the ColonCancerCheck Primary Care Invitation Pilot (the Pilot) about the mailed invitation, colorectal cancer (CRC) screening in general, and their specific screening experiences. Design Qualitative study with 6 focus group sessions, each 1.5 hours in length. Setting Hamilton, Ont; Ottawa, Ont; and Thunder Bay, Ont. Participants Screening-eligible adults, aged 50 years and older, who received a Pilot invitation for CRC screening. Methods The focus groups were conducted by a trained moderator and were audiorecorded and transcribed verbatim. The transcripts were analyzed using grounded-theory techniques facilitated by the use of electronic software. Main findings Key themes related to the invitation letter, the role of the family physician, direct mailing of the fecal occult blood testing (FOBT) kit, and alternate CRC screening promotion strategies were identified. Specifically, participants suggested the letter content should use stronger, more powerful language to capture the reader’s attention. The importance of the family physician was endorsed, although participants favoured clarification of the physician and program roles in the actual mailed invitation. Participants expressed support for directly mailing FOBT kits to individuals, particularly those with successful previous test completion, and for communication of both negative and positive screening results. Conclusion This study yielded a number of important findings including strategies to optimize letter content, support for directly mailed FOBT kits, and strategies to report results that might be highly relevant to other health programs where population-based CRC screening is being considered. PMID:24336559

  13. Colon Polyps

    MedlinePlus

    ... polyps important? Rochester, Minn.: Mayo Foundation for Medical Education and Research; 2012. Elmunzer BJ. Endoscopic resection of sessile colon polyps. Gastroenterology. 2013;144:30. Baron TH, et al. Recommended intervals between screening and surveillance colonoscopies. Mayo Clinic Proceedings. ...

  14. Solar UV-radiation, vitamin D and skin cancer surveillance in organ transplant recipients (OTRs).

    PubMed

    Reichrath, Jörg; Nürnberg, Bernd

    2008-01-01

    The introduction of organ transplantation in clinical medicine has resulted in a constantly increasing, large population of patients that are chronically on immunosuppressive medication. It is well known that skin cancer, especially SCC, in this population has higher incidence rates, behaves more aggressively and has higher rates of metastasis. OTRs who have been treated for many years with immunosuppressive medication are at the highest risk for developing malignant skin tumors. Therefore, the intensity of surveillance for cutaneous lesions is of high importance in OTRs. A full-body skin exam at least once a year and more frequently if skin cancer or precancerous cutaneous lesions develop is recommended. Clinicians should not hesitate to biopsy or to surgically excise any suspicious skin lesion. Of high importance is also the education of OTRs about their increased risk. Protection against solar and artificial UV-radiation and monthly self-examinations are good ways to prevent and to recognize any new suspicious skin lesions. Patients are advised to always wear solar UV-radiation protection (e.g., clothing, sunscreen) before going outdoors. However, investigations have revealed that solar UV-B-exposure and serum 25(OH)D levels positively correlate with decreased risk for various internal malignancies (e.g., breast, colon, prostate and ovarian cancer) and other severe diseases. As we have shown previously, renal transplant recipients are at high risk of vitamin D deficiency. A sunscreen with a sun protection factor (SPF)-8 reduces the skin's production of vitamin D by 95%. Clothing completely blocks all solar UVB-radiation and this prevents any vitamin D production. Therefore, it is important to detect and treat vitamin D deficiency in solid organ transplant recipients. Optimal management of these patients requires communication between the transplant teams and the treating dermatologist and other clinicians. For advanced or metastatic disease, collaboration

  15. Differential expression of nanog1 and nanogp8 in colon cancer cells

    SciTech Connect

    Ishiguro, Tatsuya; Sato, Ai; Ohata, Hirokazu; Sakai, Hiroaki; Nakagama, Hitoshi; Okamoto, Koji

    2012-02-10

    Highlights: Black-Right-Pointing-Pointer Nanog is expressed in a majority of colon cancer cell lines examined. Black-Right-Pointing-Pointer Both nanog1 and nanogp8 are expressed in colon cancer cells with varying ratios. Black-Right-Pointing-Pointer Nanog mediates cell proliferation of colon cancer cells. Black-Right-Pointing-Pointer Nanog predominantly localizes in cytoplasm of colon cancer cells. -- Abstract: Nanog, a homeodomain transcription factor, is an essential regulator for promotion of self-renewal of embryonic stem cells and inhibition of their differentiation. It has been demonstrated that nanog1 as well as nanogp8, a retrogene of nanog1, is preferentially expressed in advanced stages of several types of cancer, suggesting their involvement during cancer progression. Here, we investigated the expression of Nanog in well-characterized colon cancer cell lines. Expression of Nanog was detectable in 5 (HCT116, HT29, RKO, SW48, SW620) out of seven cell lines examined. RNA expression analyses of nanog1 and nanogp8 indicated that, while nanog1 was a major form in SW620 as well as in teratoma cells Tera-2, nanogp8 was preferentially expressed in HT29 and HCT116. In accordance with this, shRNA-mediated knockdown of nanog1 caused the reduction of Nanog in SW620 but not in HT29. Inhibition of Nanog in SW620 cells negatively affected cell proliferation and tumor formation in mouse xenograft. Biochemical subcellular fractionation and immunostaining analyses revealed predominant localization of Nanog in cytoplasm in SW620 and HT29, while it was mainly localized in nucleus in Tera-2. Our data indicate that nanog1 and nanogp8 are differentially expressed in colon cancer cells, and suggest that their expression contributes to proliferation of colon cancer cells.

  16. The influence of travel time on breast cancer characteristics, receipt of primary therapy, and surveillance mammography.

    PubMed

    Onega, Tracy; Cook, Andrea; Kirlin, Beth; Shi, Xun; Alford-Teaster, Jennifer; Tuzzio, Leah; Buist, Diana S M

    2011-08-01

    Travel time has been shown to influence some aspects of cancer characteristics at diagnosis and care for women with breast cancer, but important gaps remain in our understanding of its impact. We examined the influence of travel time to the nearest radiology facility on breast cancer characteristics, treatment, and surveillance for women with early-stage invasive breast cancer. We included 1,012 women with invasive breast cancer (stages I and II) who had access to care within an integrated health care delivery system in western Washington State. The travel times to the nearest radiology facility were calculated for all the U.S. Census blocks within the study area and assigned to women based on residence at diagnosis. We collected cancer characteristics, primary and adjuvant therapies, and surveillance mammography for at least 2.5 years post diagnosis and used multivariable analyses to test the associations of travel time. The majority of women (68.6%) lived within 20 min of the nearest radiology facility, had stage I disease (72.7%), received breast conserving therapy (68.7%), and had annual surveillance mammography the first 2 years after treatment (73.7%). The travel time was not significantly associated with the stage or surveillance mammography after adjusting for covariates. Primary therapy was significantly related to travel time, with greater travel time (>30 min vs. ≤ 10 min) associated with a higher likelihood of mastectomy compared to breast conserving surgery (RR = 1.53; 95% CI, 1.16-2.01). The travel time was not associated with the stage at diagnosis or surveillance mammography receipt. The travel time does seem to influence the type of primary therapy among women with breast cancer, suggesting that women may prefer low frequency services, such as mastectomy, if geographic access to a radiology facility is limited.

  17. Colon polyp model use for educating about colorectal cancer screening in the Iowa Research Network.

    PubMed

    Daly, Jeanette M; Xu, Yinghui; Levy, Barcey T

    2014-06-01

    Providing a model of a colon segment with an adenomatous polyp and cancer can help to educate patients about the adenoma to carcinoma sequence and how this sequence can be interrupted with appropriate testing. The purpose of this study was to assess the use of a three-dimensional colon model with polyps and cancer provided to family physicians or nurses in some Iowa Research Network family physician offices. Colon models were provided to 117 family medicine healthcare providers interested in colorectal cancer screening. Using a mailed survey and follow-up telephone calls to non-responders, 81 (69%) questionnaires were returned. Thirty-six (44%) of the respondents reported they had used the model, 33 (41%) reported they used the model for a mean 16% of their patients in a month's time, 31 (38%) reported using the model to teach patients about the colon and polyps prior to a colonoscopy. Other model use described by respondents included educating staff to promote patient willingness for colonoscopies, demonstrating the need for colon cancer screening, and teaching patients about annual fecal occult blood tests. Respondents agreed that anatomical models are helpful for patient education, the design of the colon model was good, and that it facilitated demonstration of colon polyps. Possible recommendations for an office-wide adoption of an anatomical model would be an in-service for all employees and a standard location for finding the model.

  18. A rare presentation of locally re-recurrent colon cancer involving the iliac bone and a review of the literature.

    PubMed

    Schumacher, Andrew; Babikir, Osman Mahdi; Abboud, Amer; Theodorakis, Spyridon

    2014-10-29

    Colorectal cancer is a leading cause of cancer death in the USA. While locally advanced rectal cancer involving bone has been described extensively, colon cancer locally involving bone has only been described, to our knowledge, in a single case report. In this case report, we describe the presentation and treatment of locally advanced re-recurrent colon cancer involving the iliac bone. We also discuss the available literature on treatment for recurrent and re-recurrent colorectal cancer.

  19. A rare presentation of locally re-recurrent colon cancer involving the iliac bone and a review of the literature

    PubMed Central

    Schumacher, Andrew; Mahdi Babikir, Osman; Abboud, Amer; Theodorakis, Spyridon

    2014-01-01

    Colorectal cancer is a leading cause of cancer death in the USA. While locally advanced rectal cancer involving bone has been described extensively, colon cancer locally involving bone has only been described, to our knowledge, in a single case report. In this case report, we describe the presentation and treatment of locally advanced re-recurrent colon cancer involving the iliac bone. We also discuss the available literature on treatment for recurrent and re-recurrent colorectal cancer. PMID:25355743

  20. Nanocytology of rectal colonocytes to assess risk of colon cancer based on field cancerization.

    PubMed

    Damania, Dhwanil; Roy, Hemant K; Subramanian, Hariharan; Weinberg, David S; Rex, Douglas K; Goldberg, Michael J; Muldoon, Joseph; Cherkezyan, Lusik; Zhu, Yuanjia; Bianchi, Laura K; Shah, Dhiren; Pradhan, Prabhakar; Borkar, Monica; Lynch, Henry; Backman, Vadim

    2012-06-01

    Developing a minimally invasive and cost-effective prescreening strategy for colon cancer is critical because of the impossibility of conducting colonoscopy on the entire at-risk population. The concept of field carcinogenesis, in which normal-appearing tissue away from a tumor has molecular and, consequently, nano-architectural abnormalities, offers one attractive approach to identify high-risk patients. In this study, we investigated whether the novel imaging technique partial wave spectroscopic (PWS) microscopy could risk-stratify patients harboring precancerous lesions of the colon, using an optically measured biomarker (L(d)) obtained from microscopically normal but nanoscopically altered cells. Rectal epithelial cells were examined from 146 patients, including 72 control patients, 14 patients with diminutive adenomas, 20 patients with nondiminutive/nonadvanced adenomas, 15 patients with advanced adenomas/high-grade dysplasia, 12 patients with genetic mutation leading to Lynch syndrome, and 13 patients with cancer. We found that the L(d) obtained from rectal colonocytes was well correlated with colon tumorigenicity in our patient cohort and in an independent validation set of 39 additional patients. Therefore, our findings suggest that PWS-measured L(d) is an accurate marker of field carcinogenesis. This approach provides a potential prescreening strategy for risk stratification before colonoscopy.

  1. Nanocytology of rectal colonocytes to assess risk of colon cancer based on field cancerization

    PubMed Central

    Damania, Dhwanil; Roy, Hemant K.; Subramanian, Hariharan; Weinberg, David S.; Rex, Douglas K.; Goldberg, Michael J.; Muldoon, Joseph; Cherkezyan, Lusik; Zhu, Yuanjia; Bianchi, Laura K.; Shah, Dhiren; Pradhan, Prabhakar; Borkar, Monica; Lynch, Henry; Backman, Vadim

    2013-01-01

    Developing a minimally invasive and cost effective pre-screening strategy for colon cancer is critical, because of the impossibility of performing colonoscopy on the entire at-risk population. The concept of field carcinogenesis, in which normal-appearing tissue away from a tumor has molecular and, consequently, nano-architectural abnormalities, offers one attractive approach to identify high-risk patients. In this study, we investigated whether the novel imaging technique partial-wave spectroscopic (PWS) microscopy could risk-stratify patients harboring precancerous lesions of the colon, using an optically measured biomarker (Ld) obtained from microscopically normal but nanoscopically altered cells. Rectal epithelial cells were examined from 146 patients, including 72 control patients, 14 patients with diminutive adenomas, 20 patients with non-advanced-non-diminutive adenomas, 15 patients with advanced adenomas/high-grade dysplasia, 12 patients with genetic mutation leading to Lynch syndrome, and 13 cancer patients. We found that the Ld obtained from rectal colonocytes was well-correlated with colon tumorigenicity in our patient cohort and in an independent validation set of 39 additional patients. Therefore, our findings suggest that PWS-measured Ld is an accurate marker of field carcinogenesis. This approach provides a potential pre-screening strategy for risk stratification before colonoscopy. PMID:22491589

  2. Management of colon cancer: resource-stratified guidelines from the Asian Oncology Summit 2012.

    PubMed

    Ku, Geoffrey; Tan, Iain Beehuat; Yau, Thomas; Boku, Narikazu; Laohavinij, Sudsawat; Cheng, Ann-Lii; Kang, Yoon-Koo; de Lima Lopes, Gilberto

    2012-11-01

    Colon cancer is seen with increasing frequency in the Asia-Pacific region, and it is one of the most important causes of cancer mortality worldwide. This article reviews the available evidence for optimum management of colon cancer-in particular, with respect to screening and early detection of colon cancer, laparoscopic surgical treatment, adjuvant treatment of individuals with high-risk stage II and stage III cancer, palliative treatment of patients with metastatic disease, and management of resectable and potentially resectable metastases-and how these strategies can be applied in Asian countries with different levels of health-care resources and economic development, stratified by basic, limited, enhanced, and maximum resource levels.

  3. Impact of anaesthetic technique on survival in colon cancer: a review of the literature.

    PubMed

    Vogelaar, F Jeroen; Lips, Daan J; van Dorsten, Frank R C; Lemmens, Valery E; Bosscha, Koop

    2016-02-01

    An oncological surgical resection is the mainstay of treatment for potentially curable colon cancer. At the time of surgery, a large fraction of patients do harbour-although not visibly-minimal residual disease at the time of surgery. The immunosuppression that accompanies surgery may have an effect on disease recurrence and survival. Regional or neuraxial anaesthetic techniques like epidural anaesthesia may suppress immune function less than opioid analgesia, by reducing stress response and significantly reducing exposure to opioids. Consistent with this hypothesis, regional anaesthetic techniques have been associated with lower recurrence rates in breast cancer and prostate cancer. Results for colon cancer, however, are contradictory. In this review of the literature we describe all studies addressing the association of the use of epidural anaesthesia and survival in colon cancer surgery.

  4. MicroRNA-302a Functions as a Putative Tumor Suppressor in Colon Cancer by Targeting Akt

    PubMed Central

    Sun, Shengjie; Zhang, Guoqing; Wu, Zhiyong; Shi, Weiwei; Yang, Bo; Li, Ying

    2014-01-01

    Micro RNAs (miRNAs) are important regulators involved in various physical and pathological processes, including cancer. The miRNA-302 family has been documented as playing a critical role in carcinogenesis. In this study, we investigated the role of miRNA-302a in colon cancer. MiRNA-302a expression was detected in 44 colon cancer tissues and 10 normal colon tissues, and their clinicopathological significance was analyzed. Cell proliferation and cell cycle analysis were performed on colon cancer cells that stably expressed miRNA-302a. The target gene of miRNA-302a and the downstream pathway were further investigated. Compared with normal colon tissues, miRNA-302a expression was downregulated in colon cancer tissues. Overexpression of miRNA-302a induced G1/S cell cycle arrest in colon cancer cells, and suppressed colon cancer cell proliferation both in vitro and in vivo. Furthermore, miRNA-302a inhibited AKT expression by directly binding to its 3′ untranslated region, resulting in subsequent alterations of the AKT-GSK3β-cyclin D1 pathway. These results reveal miRNA-302a as a tumor suppressor in colon cancer, suggesting that miRNA-302a may be used as a potential target for therapeutic intervention in colon cancer. PMID:25542007

  5. Chemopreventive and Therapeutic Effects of Edible Berries: A Focus on Colon Cancer Prevention and Treatment.

    PubMed

    Afrin, Sadia; Giampieri, Francesca; Gasparrini, Massimiliano; Forbes-Hernandez, Tamara Y; Varela-López, Alfonso; Quiles, José L; Mezzetti, Bruno; Battino, Maurizio

    2016-01-30

    Colon cancer is one of the most prevalent diseases across the world. Numerous epidemiological studies indicate that diets rich in fruit, such as berries, provide significant health benefits against several types of cancer, including colon cancer. The anticancer activities of berries are attributed to their high content of phytochemicals and to their relevant antioxidant properties. In vitro and in vivo studies have demonstrated that berries and their bioactive components exert therapeutic and preventive effects against colon cancer by the suppression of inflammation, oxidative stress, proliferation and angiogenesis, through the modulation of multiple signaling pathways such as NF-κB, Wnt/β-catenin, PI3K/AKT/PKB/mTOR, and ERK/MAPK. Based on the exciting outcomes of preclinical studies, a few berries have advanced to the clinical phase. A limited number of human studies have shown that consumption of berries can prevent colorectal cancer, especially in patients at high risk (familial adenopolyposis or aberrant crypt foci, and inflammatory bowel diseases). In this review, we aim to highlight the findings of berries and their bioactive compounds in colon cancer from in vitro and in vivo studies, both on animals and humans. Thus, this review could be a useful step towards the next phase of berry research in colon cancer.

  6. Prospective of Colon Cancer Treatments and Scope for Combinatorial Approach to Enhanced Cancer Cell Apoptosis

    PubMed Central

    Mishra, Jayshree; Dromund, Joe; Quazi, Sohel H.; Karanki, Satya Sridhar; Shaw, JJ; Chen, Ben; Kumar, Narendra

    2012-01-01

    Colorectal cancer is the leading cause of cancer-related mortality in the western world. It is also the third most common cancer diagnosed in both men and women in the United States with a recent estimate for new cases of colorectal cancer in the year 2012 being around 103,170. Various risk factors for colorectal cancer include life-style, diet, age, personal and family history, and racial and ethnic background. While a few cancers are certainly preventable but this does not hold true for colon cancer as it is often detected in its advanced stage and generally not diagnosed until symptoms become apparent. Despite the fact that several options are available for treating this cancer through surgery, chemotherapy, radiation therapy, immunotherapy, and nutritional-supplement therapy, but the success rates are not very encouraging when used alone where secondary complications appear in almost all these therapies. To maximize the therapeutic-effects in patients, combinatorial approaches are essential. In this review we have discussed the therapies previously and currently available to patients diagnosed with colorectal-cancer, focus on some recent developments in basic research that has shaded lights on new therapeutic-concepts utilizing macrophages/dendritic cells, natural killer cells, gene delivery, siRNA-, and microRNA-technology, and specific-targeting of tyrosine kinases that are either mutated or over-expressed in the cancerous cell to treat these cancer. Potential strategies are discussed where these concepts could be applied to the existing therapies under a comprehensive approach to enhance the therapeutic effects. PMID:23098684

  7. Annual surveillance mammography after early-stage breast cancer and breast cancer mortality

    PubMed Central

    Paszat, L.F.; Sutradhar, R.; Gu, S.; Rakovitch, E.

    2016-01-01

    Background After treatment for early-stage breast cancer (bca), annual surveillance mammography (asm) is recommended based on the assumption that early detection of an invasive ipsilateral breast tumour recurrence or subsequent invasive contralateral primary bca reduces bca mortality. Methods We studied women with unilateral early-stage bca treated by breast-conserving surgery from 1994 to 1997 who subsequently developed an ipsilateral recurrence or contralateral primary more than 24 months after initial diagnosis, without prior regional or distant metastases. Annual surveillance mammography was defined as 2 episodes of bilateral mammography 11–18 months apart during the 2 years preceding the ipsilateral recurrence or contralateral primary. The association between asm and bca death was evaluated using a Cox proportional hazards model. Results We identified 669 women who experienced invasive ipsilateral recurrence (n = 455) or a contralateral primary (n = 214) at a median interval of 53 months [interquartile range (iqr): 37–72 months] after initial diagnosis, 64.7% of whom had received asm during the preceding 2 years. The median interval between the 2 bilateral mammograms was 12.3 months (iqr: 11.9–13.0 months), and the median interval between the 2nd mammogram and histopathologic confirmation of ipsilateral recurrence or contralateral primary was 1.5 months (iqr: 0.8–3.9 months). Median followup after ipsilateral recurrence or contralateral primary was 7.76 years (iqr: 3.68–9.81 years). The adjusted hazard ratio for bca death associated with asm was 0.86 (95% confidence limits: 0.63, 1.16). Conclusions Annual surveillance mammography was associated with a modestly lowered hazard ratio for bca death. PMID:28050142

  8. Therapeutic aspects of c-MYC signaling in inflammatory and cancerous colonic diseases

    PubMed Central

    Sipos, Ferenc; Firneisz, Gábor; Műzes, Györgyi

    2016-01-01

    Colonic inflammation is required to heal infections, wounds, and maintain tissue homeostasis. As the seventh hallmark of cancer, however, it may affect all phases of tumor development, including tumor initiation, promotion, invasion and metastatic dissemination, and also evasion immune surveillance. Inflammation acts as a cellular stressor and may trigger DNA damage or genetic instability, and, further, chronic inflammation can provoke genetic mutations and epigenetic mechanisms that promote malignant cell transformation. Both sporadical and colitis-associated colorectal carcinogenesis are multi-step, complex processes arising from the uncontrolled proliferation and spreading of malignantly transformed cell clones with the obvious ability to evade the host’s protective immunity. In cells upon DNA damage several proto-oncogenes, including c-MYC are activated in parelell with the inactivation of tumor suppressor genes. The target genes of the c-MYC protein participate in different cellular functions, including cell cycle, survival, protein synthesis, cell adhesion, and micro-RNA expression. The transcriptional program regulated by c-MYC is context dependent, therefore the final cellular response to elevated c-MYC levels may range from increased proliferation to augmented apoptosis. Considering physiological intestinal homeostasis, c-MYC displays a fundamental role in the regulation of cell proliferation and crypt cell number. However, c-MYC gene is frequently deregulated in inflammation, and overexpressed in both sporadic and colitis-associated colon adenocarcinomas. Recent results demonstrated that endogenous c-MYC is essential for efficient induction of p53-dependent apoptosis following DNA damage, but c-MYC function is also involved in and regulated by autophagy-related mechanisms, while its expression is affected by DNA-methylation, or histone acetylation. Molecules directly targeting c-MYC, or agents acting on other genes involved in the c-MYC pathway could be

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

    PubMed

    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 <0.01) and a non-statistically significant increase in fruit/juice consumption (0.1 serving), with larger fruit/vegetable changes in African Americans than Whites. Controls increased physical activity and supplement use and fewer reported arthritic symptoms (P < 0.05). Survivors who were older and female had an almost 3 times higher likelihood of having used at least one new dietary supplement post-diagnosis, whereas being retired correlated with increased vegetable intake, all P < 0.05. Having more barriers to increasing fruit/vegetable intake was inversely associated with taking a new supplement (P < 0.05 only in controls). 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.

  10. Global surveillance of cancer survival 1995–2009: analysis of individual data for 25 676 887 patients from 279 population-based registries in 67 countries (CONCORD-2)

    PubMed Central

    Allemani, Claudia; Weir, Hannah K; Carreira, Helena; Harewood, Rhea; Spika, Devon; Wang, Xiao-Si; Bannon, Finian; Ahn, Jane V; Johnson, Christopher J; Bonaventure, Audrey; Marcos-Gragera, Rafael; Stiller, Charles; Silva, Gulnar Azevedo e; Chen, Wan-Qing; Ogunbiyi, Olufemi J; Rachet, Bernard; Soeberg, Matthew J; You, Hui; Matsuda, Tomohiro; Bielska-Lasota, Magdalena; Storm, Hans; Tucker, Thomas C; Coleman, Michel P

    2015-01-01

    Summary Background Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. Methods Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15–99 years) and 75 000 children (age 0–14 years) diagnosed with cancer during 1995–2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. Findings 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005–09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15–19% in North America, and as low as 7–9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10–20% between 1995–99 and 2005–09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer

  11. Dairy cattle serum and milk factors contributing to the risk of colon and breast cancers.

    PubMed

    zur Hausen, Harald; de Villiers, Ethel-Michele

    2015-08-15

    The analysis of published epidemiological data on colon and breast cancer reveals a remarkable concordance for most regions of the world. A low incidence for both cancers has been recorded in Mongolia and Bolivia. Discrepant data, however, have been reported for India, Japan and Korea. In India, the incidence of breast cancer is significantly higher than for colon cancer, in Japan and Korea colon cancer exceeds by far the rate of breast cancer. Here, studies are summarized pointing to a species-specific risk for colon cancer after consumption of beef originating from dairy cattle. Uptake of dairy products of Bos taurus-derived milk cattle, particularly consumed at early age, is suggested to represent one of the main risk factors for the development of breast cancer. A recent demonstration of reduced breast cancer rates in individuals with lactose intolerance (Ji et al., Br J Cancer 2014; 112:149-52) seems to be in line with this interpretation. Species-specific risk factors for these cancers are compatible with the transmission of different infectious factors transferred via meat or dairy products. Countries with discordant rates of colon and breast cancer reveal a similar discordance between meat and milk product consumption of dairy cattle. The recent isolation of a larger number of novel presumably viral DNAs from serum, meat and dairy products of healthy dairy cows, at least part of them infectious for human cells, deserves further investigation. Systemic infections early in life, resulting in latency and prevention of subsequent infections with the same agent by neutralizing antibodies, would require reconsideration of ongoing prospective studies conducted in the adult population.

  12. Surveillance Recommendations in Reducing Risk of and Optimally Managing Breast Cancer-Related Lymphedema

    PubMed Central

    Ostby, Pamela L.; Armer, Jane M.; Dale, Paul S.; Van Loo, Margaret J.; Wilbanks, Cassie L.; Stewart, Bob R.

    2014-01-01

    Breast cancer survivors are at increased risk for the development of breast cancer-related lymphedema (BCRL), a chronic, debilitating, and disfiguring condition that is progressive and requires lifelong self-management of symptoms. It has been reported that over 40% of the 2.5 million breast cancer survivors in the United States may meet the criteria for BCRL during their lifetimes. Ongoing surveillance, beginning with pre-operative assessment, has been effective in identifying subclinical lymphedema (LE). A prospective model for surveillance is necessary in order to detect BCRL at an early stage when there is the best chance to reduce risk or slow progression. Physical methods for monitoring and assessment, such as circumferential arm measures, perometry, bioimpedance; exercise programs; prophylactic and early-intervention compression garments; and referral for complete decongestive therapy are all interventions to consider in the development of a BCRL surveillance program. In addition, supportive-educative programs and interactive engagement for symptom self-management should also be implemented. The importance of interdisciplinary collaboration is integral to the success of an effective personalized medicine program in breast cancer-related lymphedema surveillance. PMID:25563360

  13. Elevated Prostate Health Index (phi) and Biopsy Reclassification During Active Surveillance of Prostate Cancer.

    PubMed

    Andreas, Darian; Tosoian, Jeffrey J; Landis, Patricia; Wolf, Sacha; Glavaris, Stephanie; Lotan, Tamara L; Schaeffer, Edward M; Sokoll, Lori J; Ross, Ashley E

    2016-07-01

    The Prostate Health Index (phi) has been FDA approved for decision-making regarding prostate biopsy. Phi has additionally been shown to positively correlate with tumor volume, extraprostatic disease and higher Gleason grade tumors. Here we describe a case in which an elevated phi encouraged biopsy of a gentleman undergoing active surveillance leading to reclassification of his disease as high risk prostate cancer.

  14. Intussusception of Rectosigmoid Colon Cancer Mimicking a Pedunculated Tumor

    PubMed Central

    Saigusa, Susumu; Ohi, Masaki; Imaoka, Hiroki; Shimura, Tadanobu; Inoue, Yasuhiro; Kusunoki, Masato

    2014-01-01

    Intussusception in adults is a rare phenomenon involving the colon in approximately 20% of cases. A 65-year-old man was hospitalized with anorexia, anemia, dehydration, and melena. Digital rectal examination revealed a palpable mass approximately 5 cm from the anal verge. The mass moved between the rectosigmoid colon and the rectum below the peritoneal reflection during radiographic examinations and during sigmoidoscopy. We strongly suspected a rectosigmoid pedunculated tumor and performed a low anterior resection. Intraoperatively we observed intussusception of the rectosigmoid colon with easy manual reduction. The tumor was palpable in the rectosigmoid colon. The postoperative course was uneventful. This case illustrates intussusception of a rectosigmoid type 1 colon adenocarcinoma mimicking a pedunculated tumor. PMID:24963434

  15. Simultaneous inhibition of ATR and PARP sensitizes colon cancer cell lines to irinotecan

    PubMed Central

    Abu-Sanad, Atlal; Wang, Yunzhe; Hasheminasab, Fatemeh; Panasci, Justin; Noë, Alycia; Rosca, Lorena; Davidson, David; Amrein, Lilian; Sharif-Askari, Bahram; Aloyz, Raquel; Panasci, Lawrence

    2015-01-01

    Enhanced DNA damage repair is one mechanism involved in colon cancer drug resistance. Thus, targeting molecular components of repair pathways with specific small molecule inhibitors may improve the efficacy of chemotherapy. ABT-888 and VE-821, inhibitors of poly-ADP-ribose-polymerase (PARP) and the serine/threonine-kinase Ataxia telangiectasia related (ATR), respectively, were used to treat colon cancer cell lines in combination with the topoisomerase-I inhibitor irinotecan (SN38). Our findings show that each of these DNA repair inhibitors utilized alone at nontoxic single agent concentrations resulted in sensitization to SN38 producing a 1.4–3 fold reduction in the 50% inhibitory concentration (IC50) of SN38 in three colon cancer cell lines. When combined together, nontoxic concentrations of ABT-888 and VE-821 produced a 4.5–27 fold reduction in the IC50 of SN38 with the HCT-116 colon cancer cells demonstrating the highest sensitization as compared to LoVo and HT-29 colon cancer cells. Furthermore, the combination of all three agents was associated with maximal G2 −M arrest and enhanced DNA-damage (γH2AX) in all three colon cancer cell lines. The mechanism of this enhanced sensitization was associated with: (a) maximal suppression of SN38 induced PARP activity in the presence of both inhibitors and (b) ABT-888 producing partial abrogation of the VE-821 enhancement of SN38 induced DNA-PK phosphorylation, resulting in more unrepaired DNA damage; these alterations were only present in the HCT-116 cells which have reduced levels of ATM. This novel combination of DNA repair inhibitors may be useful to enhance the activity of DNA damaging chemotherapies such as irinotecan and help produce sensitization to this drug in colon cancer. PMID:26257651

  16. Proportion of Colon Cancer Attributable to Lifestyle in a Cohort of US Women

    PubMed Central

    Giovannucci, Edward; Willett, Walter

    2015-01-01

    Background Many modifiable lifestyle factors have been associated with colon cancer risk, but less is known about their effect on disease when considered together. Estimating the proportion of colon cancer cases that could be prevented by the adoption of combined modifiable lifestyle behaviors will provide important insights into disease prevention. Methods In the Nurses’ Health Study, we defined a low-risk group according to a combination of six factors: body-mass index < 25kg/m2, physical activity of ≥ 21 metabolic equivalent of task per week, alcohol consumption ≤ 30g/day, cigarette smoking <10 pack years before the age of 30, current use of multivitamins for ≥ 15 years, and total calcium intake ≥700mg/day. A composite risk score index was created and the population attributable risk(PAR%) was calculated after accounting for other known risk or protective factors. Results We documented 1,127 colon cancer cases among 81,092 over 24 years of follow-up. Compared to women in the lowest-risk category, the women at all other exposure levels had a hazard ratio of colon cancer of 1.81(95% confidence interval, 1.15-2.85). The score index was significantly and linearly related to an increasing risk of colon cancer (P-value for trend <0.0001). The PAR% of the six risk factors considered together in relation to colon cancer was 0.37(95%CI: 0.09-0.60). When regular aspirin use(two tablets/week for 6 or more years) was included with the other low-risk behaviors, the PAR% increased to 0.43(95%CI: 0.14-0.65). Conclusions Beyond the known benefit from colonoscopy/sigmoidoscopy, key behavior modifications and adherence to a healthy lifestyle could avoid approximately 37% of colon cancer cases among women. PMID:26092381

  17. Resveratrol Treatment Inhibits Proliferation of and Induces Apoptosis in Human Colon Cancer Cells

    PubMed Central

    Feng, Miao; Zhong, Lu-Xing; Zhan, Zheng-Yu; Huang, Zhi-Hao; Xiong, Jian-Ping

    2016-01-01

    Background Resveratrol, a natural isolate from plant sources, has a long and important history in traditional Chinese medicine. In the present study we investigated the effect of resveratrol on human colon cancer cell lines. Material/Methods We used the Cell Counting kit-8 (CCK-8) for determination of colon cancer cell viability. Apoptosis induction was analyzed using the DeadEnd™ Colorimetric TUNEL System (Promega, Madison, WI, USA). The siRNA Transfection Reagent kit (Santa Cruz Biotechnology, Inc.) was used for the administration of COX-2 silencer RNA (siRNA) into the colon cancer cells. Primer Express® software for Real-Time PCR ver. 3.0 (Applied Biosystems, Foster City, CA, USA) was used to prepare the primers for RT-PCR. Results The results revealed that exposure of colon cancer cells to resveratrol inhibited cell viability. Resveratrol exhibited a significant inhibitory effect on cell viability at 30 μM concentration after 48 h of exposure. We observed that 30-μM doses of resveratrol for 72 h led to 18, 29, and 34% reduction in the viability of HCA-17, SW480, and HT29 cells, respectively. It also significantly induced apoptosis in both of the tested carcinoma cell lines. The population of apoptotic cells in HCA-17 and SW480 cell lines after 48 h of resveratrol treatment was 59.8±4 and 67.2±4%, respectively, compared to 2.3±1% in the control cells. The colon cancer cells exposed to resveratrol showed significantly lower cyclooxygenase-2 and prostaglandin receptor expression. Treatment of colon cancer cells with the inhibitor of cyclooxygenase-2, indomethacin, and administration of silencer RNA for cyclooxygenase-2 also produced similar results. Conclusions These findings suggest that resveratrol treatment can be a promising strategy for the treatment of colon cancer. PMID:27040803

  18. Protective effect ofAgave salmiana fructans in azoxymethane- induced colon cancer in Wistar rats.

    PubMed

    Dávila-Céspedes, Antonio; Juárez-Flores, Bertha I; Pinos-Rodríguezc, Juan M; Aguirre-Riverab, Juan R; Oros-Ovalled, A Cuahutemoc; Loyola-Martínez, E D; Andrade-Zaldívar, Hera

    2014-10-01

    Colon cancer is a world concerning disease; it shows a high mortality rate and may be related to eating habits. Studies using inulin-like fructans, which are produced as energy supplies by several plants, have demonstrated a chemo-protective effect of these fructans in colon cancer. However, agavins a structurally different type of fructans from the Agave genus with demonstrated prebiotic effects, have been poorly studied for their possible protective effects in cancer. The aim of the present study was to evaluate the effect ofAgave fructan-rich diets in colon cancer progress using a rat model and "Agave mezcalero potosino" A. salmiana Otto ex Salm Dick, which is widely distributed in Mexico. Results showed a significant decrease (p<0.05) in early lesions of colon cancer (aberrant crypt foci) compared with the control group. These data suggest that fructans from A. salmiana may contribute to a reduction in the risk of colon cancer as well as inulin-like compounds.

  19. Polyunsaturated fatty acids trigger apoptosis of colon cancer cells through a mitochondrial pathway

    PubMed Central

    Zhang, Chengcheng; Yu, Haining; Shen, Yuzhen; Ni, Xiaofeng; Das, Undurti N.

    2015-01-01

    Introduction Colorectal cancer is common in developed countries. Polyunsaturated fatty acids (PUFAs) have been reported to possess tumoricidal action, but the exact mechanism of their action is not clear. Material and methods In the present study, we studied the effect of various n-6 and n-3 fatty acids on the survival of the colon cancer cells LoVo and RKO and evaluated the possible involvement of a mitochondrial pathway in their ability to induce apoptosis. Results It was observed that n-3 α-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid (ALA, EPA and DHA respectively) and n-6 linoleic acid, gamma-linolenic acid and arachidonic acid (LA, GLA and AA respectively) induced apoptosis of the colon cancer cells LoVo and RKO at concentrations above 120 μM (p < 0.01 compared to control). The semi-differentiated colon cancer cell line RKO was more sensitive to the cytotoxic action of PUFAs compared to the undifferentiated colon cancer cell line LoVo. PUFA-treated cells showed an increased number of lipid droplets in their cytoplasm. PUFA-induced apoptosis of LoVo and RKO cells is mediated through a mitochondria-mediated pathway as evidenced by loss of mitochondrial membrane potential, generation of ROS, accumulation of intracellular Ca2+, activation of caspase-9 and caspase-3, decreased ATP level and increase in the Bax/Bcl2 expression ratio. Conclusions PUFAs induced apoptosis of colon cancer cells through a mitochondrial dependent pathway. PMID:26528354

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

    PubMed

    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.

  1. Cigarette smoke extracts induced the colon cancer migration via regulating epithelial mesenchymal transition and metastatic genes in human colon cancer cells.

    PubMed

    Kim, Cho-Won; Go, Ryeo-Eun; Lee, Hae-Miru; Hwang, Kyung-A; Lee, Kyuhong; Kim, Bumseok; Lee, Moo-Yeol; Choi, Kyung-Chul

    2017-02-01

    There was considerable evidence that exposure to cigarette smoke is associated with an increased risk for colon cancer. Nevertheless, the mechanism underlying the relationship between cigarette smoking and colon cancer remains unclear. Moreover, there were only a few studies on effects of complexing substance contained in cigarette smoke on colon cancer. Thus, we further investigated whether cigarette smoke extract (CSE) affects the cell cycle, apoptosis and migration of human metastatic colon cancer cells, SW-620. MTT assay revealed that SW-620 cell proliferation was significantly inhibited following treatments with all CSEs, 3R4F, and two-domestic cigarettes, for 9 days in a concentration-dependent manner. Moreover, CSE treatments decreased cyclin D1 and E1, and increased p21 and p27 proteins by Western blot analysis in SW-620 cells. Additionally, the treatment of the cells with CSE contributed to these effects expressing by apoptosis-related proteins. An increased migration or invasion ability of SW-620 cells following CSE treatment was also confirmed by a scratch or fibronectin invasion assay in vitro. In addition, the protein levels of E-cadherin as an epithelial maker were down-regulated, while the mesenchymal markers, N-cadherin, snail, and slug, were up-regulated in a time-dependent manner. A metastatic marker, cathepsin D, was also down-regulated by CSE treatment. Taken together, these results indicate that CSE exposure in colon cancer cells may deregulate the cell growth by altering the expression of cell cycle-related proteins and pro-apoptotic protein, and stimulate cell metastatic ability by altering epithelial-mesenchymal transition (EMT) markers and cathepsin D expression. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 690-704, 2017.

  2. Colonoscopy Surveillance After Colorectal Cancer Resection: Recommendations of the US Multi-Society Task Force on Colorectal Cancer.

    PubMed

    Kahi, Charles J; Boland, C Richard; Dominitz, Jason A; Giardiello, Francis M; Johnson, David A; Kaltenbach, Tonya; Lieberman, David; Levin, Theodore R; Robertson, Douglas J; Rex, Douglas K

    2016-03-01

    The US Multi-Society Task Force has developed updated recommendations to guide health care providers with the surveillance of patients after colorectal cancer (CRC) resection with curative intent. This document is based on a critical review of the literature regarding the role of colonoscopy, flexible sigmoidoscopy, endoscopic ultrasound, fecal testing and CT colonography in this setting. The document addresses the effect of surveillance, with focus on colonoscopy, on patient survival after CRC resection, the appropriate use and timing of colonoscopy for perioperative clearing and for postoperative prevention of metachronous CRC, specific considerations for the detection of local recurrence in the case of rectal cancer, as well as the place of CT colonography and fecal tests in post-CRC surveillance.

  3. Prolonged Sulforaphane Treatment Activates Extracellular-Regulated Kinase 1/2 Signaling in Nontumorigenic Colon Cells but not Colon Cancer Cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sulforaphane (SFN) is a naturally occurring member of the isothiocyanate family of chemopreventive agents and the induction of cell cycle arrest and apoptosis is a key mechanism by which SFN exerts its colon cancer prevention. However, little is known about the differential effects of SFN on colon c...

  4. In vitro and In vivo Studies on Stilbene Analogs as Potential Treatment Agents for Colon Cancer

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Based upon the potential of resveratrol as a cancer chemopreventive agent, 27 stilbenes analogs were synthesized and tested against colon cancer cell line HT-29. Among these compounds, amino derivative (Z)-4-(3,5-dimethoxystyryl) aniline (4), (Z)-methyl 4-(3,5-dimethoxystyryl) benzoate (6) and (Z)-1...

  5. Even a Little Daily Activity May Boost Colon Cancer Survival: Study

    MedlinePlus

    ... counted as moderate exercise, the study authors said. Exercise benefits previously have been reported for early stage cancer ... prognosis for late-stage colon cancer. Still, "while exercise is by no ... experience a wide range of benefits from as little as 30 minutes of exercise ...

  6. Biological/chemopreventive activity of stilbenes and their effect on colon cancer.

    PubMed

    Rimando, Agnes M; Suh, Nanjoo

    2008-10-01

    Colon cancer is one of the leading causes of cancer death in men and women in Western countries. Epidemiological studies have linked the consumption of fruits and vegetables to a reduced risk of colon cancer, and small fruits are particularly rich sources of many active phytochemical stilbenes, such as resveratrol and pterostilbene. Recent advances in the prevention of colon cancer have stimulated an interest in diet and lifestyle as an effective means of intervention. As constituents of small fruits such as grapes, berries and their products, stilbenes are under intense investigation as cancer chemopreventive agents. One of the best-characterized stilbenes, resveratrol, has been known as an antioxidant and an anti-aging compound as well as an anti-inflammatory agent. Stilbenes have diverse pharmacological activities, which include cancer prevention, a cholesterol-lowering effect, enhanced insulin sensitivity, and increased lifespan. This review summarizes results related to the potential use of various stilbenes as cancer chemopreventive agents, their mechanisms of action, as well as their pharmacokinetics and efficacy for the prevention of colon cancer in animals and humans.

  7. Surveillance After Initial Treatment for Breast Cancer: A Population-Based Study of Variation In and Outcomes of Care

    DTIC Science & Technology

    1996-10-01

    Ft Detrick, MD. THIS PAGE IS UNCLASSIFIED AAD GRANT NUMBER DAMDI7-94-J-4043 TITLE: Surveillance After Initial Treatment for Breast Cancer: A...NUMBERS Surveillance After Initial Treatment for Breast Cancer: DAMDI7-94-J-4043 A Population-Based Study of Variation In and Outcomes of Care 6. AUTHOR(S...ABSTRACT (Maximum 200 We have utilized SEER and Medicare data bases to study patterns of care related to the treatment of local/regional breast cancer. In

  8. Structure-based design of peptides against HER2 with cytotoxicity on colon cancer.

    PubMed

    Cha, Nier; Han, Xiuhua; Jia, Baoqing; Liu, Yanheng; Wang, Xiaoli; Gao, Yanwei; Ren, Jun

    2017-05-01

    In this study, we found that four novel peptides designed by molecular modeling techniques were successfully applicated with cytotoxicity on colon cancer cells sw620. First, the interactions between the Herstatin and the HER2 were explored by ational-designed approaches, which were combined with homology modeling, protein/protein docking, and structural superimposition analysis. Then, based on the results derived from theoretical analysis, four novel peptides were designed, synthesized, and experimentally evaluated for biological function; it was found that they showed a remarkable enhancement on Herceptin to inhibit the genesis and development of colon cancers, and no significant side effects on normal colon cells NCM460 were observed but Doxorubicin had. These results indicated that it is a feasible way to use the well-designed peptides derived from Herstatin to enhance the efficacy of clinical drugs Herceptin and to kill colon cancer cells selectively without harming normal colon cells. We believe that our research might provide a new way to develop the potential therapies for colon cancers.

  9. Targeting Lymph Node Retrieval and Assessment in Stage II Colon Cancer: A Quality Outcome Community-Based Cancer Center Study

    PubMed Central

    Grote, Thomas; Hughes, Amy H.; Rimmer, Cathy C.; Less, Dale A.; Abernethy, Amy P.

    2008-01-01

    Purpose Adequate lymph node evaluation is required for the proper staging of colon cancer. The current recommended number of lymph nodes that should be retrieved and assessed is 12. Methods The multidisciplinary Gastrointestinal Tumor Board at the Derrick L. Davis Forsyth Regional Cancer Center reviewed and recommended that a minimum of 12 lymph nodes be examined in all cases of colon cancer to ensure proper staging. This recommendation occurred at the end of the first quarter of 2005. To ensure this new standard was being followed, an outcomes study looking at the number of lymph nodes evaluated in stage II colon cancer was initiated. All patients with stage II colon cancer diagnosed between 2004 and 2006 were reviewed. Results There was a statistically significant improvement in the number of stage II colon cancer patients with 12 or more lymph nodes evaluated. Before the Gastrointestinal Tumor Board's recommendation, 49% (40 out of 82 patients) had 12 or more lymph nodes sampled. The median number of lymph nodes evaluated was 11. After the Gastrointestinal Tumor Board's recommendation, 79% (70 out of 88 patients) had 12 or more lymph nodes sampled. The median number of lymph nodes was 16. Conclusion Multidisciplinary tumor boards can impact the quality of care of patients as demonstrated in this study. Although we do not yet have survival data on these patients, based on the previous literature referenced in this article, we would expect to see an improvement in survival rates in patients with 12 or more nodes retrieved and assessed. PMID:20856779

  10. Hes1 is involved in the self-renewal and tumourigenicity of stem-like cancer cells in colon cancer.

    PubMed

    Gao, Fei; Zhang, YuQin; Wang, ShengChun; Liu, YuanQiang; Zheng, Lin; Yang, JianQuan; Huang, Wei; Ye, YanFen; Luo, WeiRen; Xiao, Dong

    2014-02-04

    A small subpopulation of cancer cells with stem cell-like features might be responsible for tumour generation, progression, and chemoresistance. Hes1 influences the maintenance of certain stem cells and progenitor cells and the digestive systems. We found upregulated Hes1 in poorly differentiated cancer samples compared with well-differentiated tumour samples, and most of the adenocarcinomas exhibited significantly higher levels of Hes1 mRNA compared with that observed in matched normal colon samples. Moreover, Hes1 expression was found to be correlated with the expression of stem cell markers in colon cancer samples, and Hes1 upregulates the expression of stemness-related genes in colon cancer cells. In addition, Hes1 enhances the self-renewal properties of the stem-like cells by increasing the sizes of CD133+ cells and SP cells and the ability of tumour sphere formation. Additionally, the Hes1-overexpressing cells formed significantly larger and higher number of colonies, as determined through the colony and the soft agar assays. More importantly, Hes1 enhances the tumourigenicity of colon cancer cell lines in nude mice and exhibits a strong tumour-formation ability at a cell density of 1 × 10(3). Taken together, our data indicate that Hes1 induces stem-like cell self-renewal and increases the number of tumour-initiating cells in colon cancer.

  11. Use of CA-125 Tests and CT Scans for Surveillance in Ovarian Cancer

    PubMed Central

    Esselen, Katharine M.; Cronin, Angel M.; Bixel, Kristin; Bookman, Michael A.; Burger, Robert A.; Cohn, David E.; Cristea, Mihaela; Griggs, Jennifer J.; Levenback, Charles F.; Mantia-Smaldone, Gina; Meyer, Larissa A.; Matulonis, Ursula A.; Niland, Joyce C.; Sun, Charlotte; O’Malley, David M.; Wright, Alexi A.

    2016-01-01

    Importance A 2009 randomized clinical trial (RCT) demonstrated that using CA-125 tests for routine surveillance in ovarian cancer increases chemotherapy use and decreases patients’ quality of life without improving survival, compared with clinical observation. The Society of Gynecologic Oncology guidelines categorize CA-125 testing as “optional” and discourage the use of radiographic imaging for routine surveillance. To date, few studies have examined their use in clinical practice. Objective To examine the use of CA-125 tests and CT scans in clinical practice before and after the 2009 RCT and estimate the economic impact of surveillance testing. Design Prospective cohort of women diagnosed with ovarian cancer between 2004-2011 and followed through 2012. Setting Six National Cancer Institute-Designated Cancer Centers. Participants 1,241 women with ovarian cancer in clinical remission after completion of primary cytoreductive surgery and chemotherapy. Main Outcome Measures Use of CA-125 tests and CT scans before and after 2009 (n=1,241). Secondary outcomes included: the time from CA-125 doubling to retreatment among women who experienced a rise in CA-125 (n=511) before and after 2009, and the costs associated with surveillance testing using 2016 Medicare reimbursement rates. Results Use of CA-125 testing and CT scans was very similar over the study period. During 12 months of surveillance, the cumulative incidence of 3 or more CA-125 tests was 86% in 2004-2009 versus 91% in 2010-2012 (P=.95), and the cumulative incidence of more than 1 CT scan was 81% (2004-2009) versus 78% (2010-2012) (P=.50). Among women who experienced a CA-125 doubling (n=511), there was no significant difference in the time to retreatment with chemotherapy before and after 2009 (median: 2.8 months vs. 3.5 months, P=.40). Over a 12-month period, there were a mean of 4.6 CA-125 tests and 1.7 CT scans per patient, resulting in a United States population surveillance cost estimate of $1

  12. Cancer Prehabilitation for Patients Starting from Active Treatment to Surveillance

    PubMed Central

    Shun, Shiow-Ching

    2016-01-01

    The purpose of this brief summary is to introduce the concept of cancer prehabilitation and the role of oncology nurses in prehabilitation care. Cancer prehabilitation has been defined by Sliver and Baima (2013) as “a process on the cancer continuum of care that occurs between the time of cancer diagnosis and the beginning of acute treatment.” The evidence supports the notion that prehabilitation programs can improve physical and psychological health outcomes and decrease overall health care costs. The care model for cancer prehabilitation should include timely and efficient assessment throughout the care continuum with a focus on improving outcomes in cancer at every stage. During the cancer journey, three types of assessment with different aims are included: (1) prehabilitation assessment pretreatment, (2) rehabilitation assessment at early post treatment, and (3) health promotion assessment at the end of treatment. Specific prehabilitation assessment and interventions for treatment-related complications or major side-effects should be considered. Teaching, counseling, discharge planning, and coordination should also be part of an oncology nurse's role in cancer prehabilitation. It is suggested that cancer care managers or navigators be trained in the assessment of their patients’ physical and psychological status once the cancer diagnosis has been identified and the patient has decided to receive active treatment, especially for those waiting for surgery at home. Oncology nurses could increase their competence with prehabilitation care by gaining knowledge about cancer-related treatments and their outcomes for specific cancers and by strengthening the ability to assess the functional status and psychological distress of their patients. PMID:27981135

  13. Brain-derived neurotrophic factor regulates cell motility in human colon cancer.

    PubMed

    Huang, Ssu-Ming; Lin, Chingju; Lin, Hsiao-Yun; Chiu, Chien-Ming; Fang, Chia-Wei; Liao, Kuan-Fu; Chen, Dar-Ren; Yeh, Wei-Lan

    2015-06-01

    Brain-derived neurotrophic factor (BDNF) is a potent neurotrophic factor that has been shown to affect cancer cell metastasis and migration. In the present study, we investigated the mechanisms of BDNF-induced cell migration in colon cancer cells. The migratory activities of two colon cancer cell lines, HCT116 and SW480, were found to be increased in the presence of human BDNF. Heme oxygenase-1 (HO)-1 is known to be involved in the development and progression of tumors. However, the molecular mechanisms that underlie HO-1 in the regulation of colon cancer cell migration remain unclear. Expression of HO-1 protein and mRNA increased in response to BDNF stimulation. The BDNF-induced increase in cell migration was antagonized by a HO-1 inhibitor and HO-1 siRNA. Furthermore, the expression of vascular endothelial growth factor (VEGF) also increased in response to BDNF stimulation, as did VEGF mRNA expression and transcriptional activity. The increase in BDNF-induced cancer cell migration was antagonized by a VEGF-neutralizing antibody. Moreover, transfection with HO-1 siRNA effectively reduced the increased VEGF expression induced by BDNF. The BDNF-induced cell migration was regulated by the ERK, p38, and Akt signaling pathways. Furthermore, BDNF-increased HO-1 and VEGF promoter transcriptional activity were inhibited by ERK, p38, and AKT pharmacological inhibitors and dominant-negative mutants in colon cancer cells. These results indicate that BDNF increases the migration of colon cancer cells by regulating VEGF/HO-1 activation through the ERK, p38, and PI3K/Akt signaling pathways. The results of this study may provide a relevant contribution to our understanding of the molecular mechanisms by which BDNF promotes colon cancer cell motility.

  14. Defective IL-23/IL-17 Axis Protects p47phox−/− Mice from Colon Cancer

    PubMed Central

    Richter, Cornelia; Herrero San Juan, Martina; Weigmann, Benno; Bergis, Dominik; Dauber, Katrin; Muders, Michael H.; Baretton, Gustavo B.; Pfeilschifter, Josef Martin; Bonig, Halvard; Brenner, Sebastian; Radeke, Heinfried H.

    2017-01-01

    In the colon, a sophisticated balance between immune reaction and tolerance is absolutely required. Dysfunction may lead to pathologic phenotypes ranging from chronic inflammatory processes to cancer development. Two prominent modulators of colon inflammation are represented by the closely related cytokines interleukin (IL)-12 and IL-23, which initiate adaptive Th1 and Th17 immune responses, respectively. In this study, we investigated the impact of the NADPH oxidase protein p47phox, which negatively regulates IL-12 in dendritic cells, on colon cancer development in a colitis-associated colon cancer model. Initially, we found that IL-12−/− mice developed less severe colitis but are highly susceptible to colon cancer. By contrast, p47phox−/− mice showed lower tumor scores and fewer high grade tumors than wild-type (WT) littermates. Treatment with toll-like receptor 9 ligand CpG2216 significantly enhanced colitis in p47phox−/− mice, whereas tumor growth was simultaneously reduced. In tumor tissue of p47phox−/− mice, the IL-23/IL-17 axis was crucially hampered. IL-23p19 protein expression in tumor tissue correlated with tumor stage. Reconstitution of WT mice with IL-23p19−/− bone marrow protected these mice from colon cancer, whereas transplantation of WT hematopoiesis into IL-23p19−/− mice increased the susceptibility to tumor growth. Our study strengthens the divergent role of IL-12 and IL-23 in colon cancer development. With the characterization of p47phox as a novel modulator of both cytokines our investigation introduces a promising new target for antitumor strategies. PMID:28191009

  15. PGE{sub 2}-induced colon cancer growth is mediated by mTORC1

    SciTech Connect

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

    2014-09-05

    Highlights: • PGE{sub 2} activates mTORC1 in colon cancer cells. • Inhibition of mTORC1 blocks PGE{sub 2} induced colon cancer cell growth. • mTORC1 is a signaling intermediary in PGE{sub 2} induced colon cancer cell responses. - Abstract: The inflammatory prostaglandin E{sub 2} (PGE{sub 2}) cytokine plays a key role in the development of colon cancer. Several studies have shown that PGE{sub 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{sub 2}-induced colon cancer cell responses. Indeed, stimulation of LS174T cells with PGE{sub 2} increased mTORC1 activity as observed by the augmentation of S6 ribosomal protein phosphorylation, a downstream effector of mTORC1. The PGE{sub 2} EP{sub 4} receptor was responsible for transducing the signal to mTORC1. Moreover, PGE{sub 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{sub 2}-induced LS174T cell growth. Finally, stimulation of LS174T cells with PGE{sub 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{sub 2} mediated colon cancer cell growth and VEGF production. They further support a role for mTORC1 in inflammation induced tumor growth.

  16. Breast Cancer Cell Colonization of the Human Bone Marrow Adipose Tissue Niche1

    PubMed Central

    Templeton, Zach S.; Lie, Wen-Rong; Wang, Weiqi; Rosenberg-Hasson, Yael; Alluri, Rajiv V.; Tamaresis, John S.; Bachmann, Michael H.; Lee, Kitty; Maloney, William J.; Contag, Christopher H.; King, Bonnie L.

    2015-01-01

    BACKGROUND/OBJECTIVES: Bone is a preferred site of breast cancer metastasis, suggesting the presence of tissue-specific features that attract and promote the outgrowth of breast cancer cells. We sought to identify parameters of human bone tissue associated with breast cancer cell osteotropism and colonization in the metastatic niche. METHODS: Migration and colonization patterns of MDA-MB-231-fLuc-EGFP (luciferase-enhanced green fluorescence protein) and MCF-7-fLuc-EGFP breast cancer cells were studied in co-culture with cancellous bone tissue fragments isolated from 14 hip arthroplasties. Breast cancer cell migration into tissues and toward tissue-conditioned medium was measured in Transwell migration chambers using bioluminescence imaging and analyzed as a function of secreted factors measured by multiplex immunoassay. Patterns of breast cancer cell colonization were evaluated with fluorescence microscopy and immunohistochemistry. RESULTS: Enhanced MDA-MB-231-fLuc-EGFP breast cancer cell migration to bone-conditioned versus control medium was observed in 12/14 specimens (P = .0014) and correlated significantly with increasing levels of the adipokines/cytokines leptin (P = .006) and IL-1β (P = .001) in univariate and multivariate regression analyses. Fluorescence microscopy and immunohistochemistry of fragments underscored the extreme adiposity of adult human bone tissues and revealed extensive breast cancer cell colonization within the marrow adipose tissue compartment. CONCLUSIONS: Our results show that breast cancer cells migrate to human bone tissue-conditioned medium in association with increasing levels of leptin and IL-1β, and colonize the bone marrow adipose tissue compartment of cultured fragments. Bone marrow adipose tissue and its molecular signals may be important but understudied components of the breast cancer metastatic niche. PMID:26696367

  17. [Colon cancer: a rare complication in a colonic esophageal segment after coloesophagoplasty].

    PubMed

    Martín, Miguel Angel; Ferrás, Albio

    2005-01-01

    We report the case of a 65-year-old woman who presented to the Hermanos Ameijeiras Hospital in Cuba due to dysphagia for the previous 5 months. Forty years previously, she had undergone esophagocoloplasty for caustic esophagitis. Adenocarcinoma was diagnosed in the colonic interposition. The tumor was resected with oncologic margins and food transit was successfully restored.

  18. Asymptomatic Cardiac Toxicity in Long-Term Cancer Survivors: Defining the Population and Recommendations for Surveillance

    PubMed Central

    Carver, Joseph R.; Szalda, Dava; Ky, Bonnie

    2013-01-01

    Advances in the treatment of pediatric and adult cancer have reduced the mortality rates from these disorders and have led to an ever-increasing population of long-term survivors. Chemotherapy and radiotherapy may cause premature cardiac disease that may be asymptomatic or symptomatic. All patients exposed to chemotherapy with cardiotoxic potential or chest radiotherapy have stage A heart failure and the goal of surveillance and treatment is to prevent progression to stages B-D. Screening strategies, including the use of biomarkers, echocardiography, and expert opinion surveillance and treatment recommendations, are presented. PMID:23540748

  19. Glucagon-like peptide 2 in colon carcinogenesis: possible target for anti-cancer therapy?

    PubMed

    Kannen, Vinicius; Garcia, Sergio Britto; Stopper, Helga; Waaga-Gasser, Ana Maria

    2013-07-01

    The role of glucagon-like peptide 2 (GLP2) in colon tissue has been studied extensively, from the time it was discovered that GLP2 promotes intestinal growth. A large number of studies have shown potential applications for GLP2 in human therapy. However, recent data have suggested the notion that GLP2 plays a key role in colon carcinogenesis. Questions have been arisen regarding the pro-proliferative effects of GLP2 and whether they might promote intestinal healing or advance colon tumor growth. Here, we provide striking evidence to show that the physiological activities of GLP2 are closely related to cancer-related molecular pathways that have been shown to circumvent drug desensitization. We further explore the different pathways of GLP2-signaling to suggest suitable GLP2-based therapeutic strategies in colon cancer.

  20. Stromal Hedgehog signalling is downregulated in colon cancer and its restoration restrains tumour growth

    PubMed Central

    Gerling, Marco; Büller, Nikè V. J. A.; Kirn, Leonard M.; Joost, Simon; Frings, Oliver; Englert, Benjamin; Bergström, Åsa; Kuiper, Raoul V.; Blaas, Leander; Wielenga, Mattheus C. B.; Almer, Sven; Kühl, Anja A.; Fredlund, Erik; van den Brink, Gijs R.; Toftgård, Rune

    2016-01-01

    A role for Hedgehog (Hh) signalling in the development of colorectal cancer (CRC) has been proposed. In CRC and other solid tumours, Hh ligands are upregulated; however, a specific Hh antagonist provided no benefit in a clinical trial. Here we use Hh reporter mice to show that downstream Hh activity is unexpectedly diminished in a mouse model of colitis-associated colon cancer, and that downstream Hh signalling is restricted to the stroma. Functionally, stroma-specific Hh activation in mice markedly reduces the tumour load and blocks progression of advanced neoplasms, partly via the modulation of BMP signalling and restriction of the colonic stem cell signature. By contrast, attenuated Hh signalling accelerates colonic tumourigenesis. In human CRC, downstream Hh activity is similarly reduced and canonical Hh signalling remains predominantly paracrine. Our results suggest that diminished downstream Hh signalling enhances CRC development, and that stromal Hh activation can act as a colonic tumour suppressor. PMID:27492255

  1. Identification of Risk Factors for Recurrence in High-Risk Stage II Colon Cancer

    PubMed Central

    Hatano, Satoshi; Ishida, Hideyuki; Ishibashi, Keiichiro; Kumamoto, Kensuke; Haga, Norihiro; Miura, Ichiro

    2013-01-01

    To identify risk factors for recurrence in patients with stage II colon cancer, Cox proportional hazards regression analysis was performed in 194 patients with stage II colon cancer who underwent curative surgery between April 1997 and December 2008. Thirteen clinical and pathologic factors, including use of fluoropyrimidine-based adjuvant chemotherapy in 113 of the patients (58.2%), were assessed. By multivariate analysis, only obstruction, perforation, and T4-level invasion were identified as independent risk factors affecting disease-free survival (DFS) (P < 0.01). The 5-year DFS rate was 70.6% in patients with one or more risk factors (n = 68) and 96.0% in patients with no risk factors (n = 126) (P < 0.01). These results suggest that obstruction, perforation, and T4-level invasion are suitable candidates for prediction of tumor recurrence in patients with stage II colon cancer. The oxaliplatin-based adjuvant chemotherapy, which has been reported to be effective in stage III colon cancer patients, may improve the prognosis in high-risk stage II colon cancer patients. PMID:23701145

  2. Overexpression of suppressor of IKBKE 1 is associated with vincristine resistance in colon cancer cells

    PubMed Central

    Zhao, Chun-Peng; Xu, Zhong-Jie; Guo, Qing; Li, Yun-Xiao; Gao, Xiang-Zheng; Peng, Yi-You

    2016-01-01

    In a previous study, the suppressor of IKBKE 1 expression level was confirmed to be higher in vincristine (VCR)-resistant HCT-8 (HCT-8/V) colon cancer cells than in non-VCR-resistant HCT-8 cells. In the current study, IKBKE 1 expression in VCR-resistant colon cancer cells was investigated further. HCT-8 and HCT-8/V human colon cancer cells were used, and polymerase chain reaction (PCR) primers were designed to amplify the IKBKE 1 gene. Fluorescence reverse transcription-quantitative PCR (RT-qPCR) was performed to detect differences in IKBKE 1 expression between sensitive and drug-resistant colon cancer cell lines. Western blotting was performed to further observe IKBKE 1 expression. Based on the RT-qPCR and western blot results, IKBKE 1 expression was observed to be markedly higher in the HCT-8/V cells, and this difference was significant (P<0.05). Thus, IKBKE 1 expression was identified to be associated with the resistance of colon cancer cells to VCR. PMID:27882221

  3. Carvacrol inhibits proliferation and induces apoptosis in human colon cancer cells.

    PubMed

    Fan, Kai; Li, Xiaolei; Cao, Yonggang; Qi, Hanping; Li, Lei; Zhang, Qianhui; Sun, Hongli

    2015-09-01

    Colon cancer is one of the most common malignancies worldwide and has a high mortality rate. Carvacrol is a major component of oregano and thyme essential oils and shows antitumor properties. Here, we investigated the effects of carvacrol on the proliferation and apoptosis of two human colon cancer cell lines, HCT116 and LoVo, and studied the molecular mechanisms of its antitumor properties. We found that carvacrol inhibited the proliferation and migration of the two colon cancer cell lines in a concentration-dependent manner. Cell invasion was suppressed after carvacrol treatment by decreasing the expression of matrix metalloprotease-2 (MMP-2) and MMP-9. Carvacrol treatment also caused cell cycle arrest in the G2/M phase and decreased cyclin B1 expression. Finally, carvacrol induced cell apoptosis in a dose-dependent manner. At the molecular level, carvacrol downregulated the expression of Bcl-2 and induced the phosphorylation of the extracellular-regulated protein kinase and protein kinase B (p-Akt). In parallel, carvacrol upregulated the expression of Bax and c-Jun N-terminal kinase. These results indicate that carvacrol might induce apoptosis in colon cancer cells through the mitochondrial apoptotic pathway and the MAPK and PI3K/Akt signaling pathways. Together, our results suggest that carvacrol may have therapeutic potential for the prevention and treatment of colon cancer.

  4. Colon cancer and content of nitrates and magnesium in drinking water.

    PubMed

    Chiu, Hui-Fen; Tsai, Shang-Shyue; Wu, Trong-Neng; Yang, Chun-Yuh

    2010-06-01

    The objective of this study was to explore whether magnesium levels (Mg) in drinking water modify the effects of nitrate on colon cancer risk. A matched case-control study was used to investigate the relationship between the risk of death from colon cancer and exposure to nitrate in drinking water in Taiwan. All colon cancer deaths of Taiwan residents from 2003 through 2007 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cases by gender, year-of-birth, and year-of-death. Information on the levels of nitrate-nitrogen (NO3-N) and Mg in drinking water were collected from Taiwan Water Supply Corporation (TWSC). The municipality of residence for cases and controls was assumed to be the source of the subject's NO3-N and Mg exposure via drinking water. The results of our study show that there is a significant trend towards an elevated risk of death from colon cancer with increasing nitrate levels in drinking water. Furthermore, we observed evidence of an interaction between drinking water NO3-N and Mg intake via drinking water. This is the first study to report effect modification by Mg intake from drinking water on the association between NO3-N exposure and colon cancer risk.

  5. Incorporation of CEA Improves Risk Stratification in Stage II Colon Cancer.

    PubMed

    Spindler, Blake A; Bergquist, John R; Thiels, Cornelius A; Habermann, Elizabeth B; Kelley, Scott R; Larson, David W; Mathis, Kellie L

    2017-03-13

    High-risk features are used to direct adjuvant therapy for stage II colon cancer. Currently, high-risk features are identified postoperatively, limiting preoperative risk stratification. We hypothesized carcinoembryonic antigen (CEA) can improve preoperative risk stratification for stage II colon cancer. The National Cancer Database (NCDB 2004-2009) was reviewed for stage II colon adenocarcinoma patients undergoing curative intent resection. A novel risk stratification including both traditional high-risk features (T4 lesion, <12 lymph nodes sampled, and poor differentiation) and elevated CEA was developed. Unadjusted Kaplan-Meier and adjusted Cox proportional hazards analyzed overall survival. Concordance Probability Estimates (CPE) assessed discrimination. Seventy-four thousand nine hundred forty-five patients were identified; 40,844 (54.5%) had CEA levels reported and were included. Chemotherapy administration was similar between normal and elevated CEA groups (23.8 vs. 25.1%, p = 0.003). Compared to patients with CEA elevation, 5-year overall survival in patients with normal CEA was improved (74.5 vs. 63.4%, p < 0.001). Restratification incorporating CEA resulted in reclassification of 6912 patients (16.9%) from average to high risk. CPE increased for novel risk stratification (0.634 vs. 0.612, SE = 0.005). The routinely available CEA test improved risk stratification for stage II colon cancer. CEA not only may improve staging of colon cancer but may also help guide additional therapy.

  6. A case report of thyroid gland metastasis associated with lung metastasis from colon cancer.

    PubMed

    Nakamura, Keisuke; Nozawa, Keijiro; Aoyagi, Yoshiko; Ishihara, Soichiro; Matsuda, Keiji; Fukushima, Junichi; Watanabe, Toshiaki

    2011-01-01

    Thyroid gland metastasis of malignant tumors is observed in 1.9% to 9.5% of histologically examined autopsy cases. Thyroid metastasis from colon cancer is extremely rare and the prognosis is poor. Here we report a case of lung metastasis and thyroid gland metastasis following sigmoid colon cancer surgery. In 2000, a 58-year-old woman underwent a sigmoid colectomy for sigmoid colon cancer. In 2005, a metastatic lung tumor was detected by chest CT. The patient underwent a partial thoracoscopic resection of the left lung in April 2005. On a CT scan taken 3 years and 4 months after the lung resection, a tumor mass was observed in the left lung and a low-absorption region with an unclear border was seen in the left lobe of the thyroid gland. Thyroid aspiration cytology showed adenocarcinoma, and a diagnosis of thyroid gland metastasis from sigmoid colon cancer was made. In April 2008 a subtotal thyroidectomy was performed. Following surgery, the patient underwent chemotherapy with mFOLFOX6 and bevacizumab. Nevertheless a number of lung metastases and expressions of lung metastasis were subsequently observed. Histopathological examination revealed a number of metastases of differentiated papillary adenocarcinoma in the thyroid gland from colon cancer.

  7. Tussilagone suppresses colon cancer cell proliferation by promoting the degradation of β-catenin

    SciTech Connect

    Li, Hua; Lee, Hwa Jin; Ahn, Yeon Hwa; Kwon, Hye Jin; Jang, Chang-Young; Kim, Woo-Young; Ryu, Jae-Ha

    2014-01-03

    Highlights: •Tussilagone (TSL) was purified from plant as an inhibitor of Wnt/β-catenin pathway. •TSL suppressed the β-catenin/T-cell factor transcriptional activity. •The proteasomal degradation of β-catenin was induced by TSL. •TSL suppressed the Wnt/β-catenin target genes, cyclin D1 and c-myc. •TSL inhibit the proliferation of colon cancer cells. -- Abstract: Abnormal activation of the Wnt/β-catenin signaling pathway frequently induces colon cancer progression. In the present study, we identified tussilagone (TSL), a compound isolated from the flower buds of Tussilago farfara, as an inhibitor on β-catenin dependent Wnt pathway. TSL suppressed β-catenin/T-cell factor transcriptional activity and down-regulated β-catenin level both in cytoplasm and nuclei of HEK293 reporter cells when they were stimulated by Wnt3a or activated by an inhibitor of glycogen synthase kinase-3β. Since the mRNA level was not changed by TSL, proteasomal degradation might be responsible for the decreased level of β-catenin. In SW480 and HCT116 colon cancer cell lines, TSL suppressed the β-catenin activity and also decreased the expression of cyclin D1 and c-myc, representative target genes of the Wnt/β-catenin signaling pathway, and consequently inhibited the proliferation of colon cancer cells. Taken together, TSL might be a potential chemotherapeutic agent for the prevention and treatment of human colon cancer.

  8. Personalizing colon cancer adjuvant therapy: selecting optimal treatments for individual patients.

    PubMed

    Dienstmann, Rodrigo; Salazar, Ramon; Tabernero, Josep

    2015-06-01

    For more than three decades, postoperative chemotherapy-initially fluoropyrimidines and more recently combinations with oxaliplatin-has reduced the risk of tumor recurrence and improved survival for patients with resected colon cancer. Although universally recommended for patients with stage III disease, there is no consensus about the survival benefit of postoperative chemotherapy in stage II colon cancer. The most recent adjuvant clinical trials have not shown any value for adding targeted agents, namely bevacizumab and cetuximab, to standard chemotherapies in stage III disease, despite improved outcomes in the metastatic setting. However, biomarker analyses of multiple studies strongly support the feasibility of refining risk stratification in colon cancer by factoring in molecular characteristics with pathologic tumor staging. In stage II disease, for example, microsatellite instability supports observation after surgery. Furthermore, the value of BRAF or KRAS mutations as additional risk factors in stage III disease is greater when microsatellite status and tumor location are taken into account. Validated predictive markers of adjuvant chemotherapy benefit for stage II or III colon cancer are lacking, but intensive research is ongoing. Recent advances in understanding the biologic hallmarks and drivers of early-stage disease as well as the micrometastatic environment are expected to translate into therapeutic strategies tailored to select patients. This review focuses on the pathologic, molecular, and gene expression characterizations of early-stage colon cancer; new insights into prognostication; and emerging predictive biomarkers that could ultimately help define the optimal adjuvant treatments for patients in routine clinical practice.

  9. [A Case of Pseudo-Meigs Syndrome Associated with Metachronous Ovarian Metastasis from Ascending Colon Cancer].

    PubMed

    Yachi, Takafumi; Nishikawa, Shinsuke; Tokura, Tomohisa; Iwama, Masahiro; Akaishi, Takanobu; Umehara, Minoru; Umehara, Yutaka; Murata, Akihiko; Takahashi, Kenichi; Morita, Takayuki

    2015-10-01

    We experienced a case of pseudo-Meigs syndrome associated with metachronous metastasis to the ovary from ascending colon cancer. A 65-year-old woman underwent curative surgery for ascending colon cancer at another hospital. A follow-up CT carried out 3 months after the surgery revealed a right ovarian tumor and a large amount of ascites. The patient was diagnosed with ovarian metastasis from ascending colon cancer with carcinomatous peritonitis. Palliative care was recommended, and she presented at our department for a second opinion. In spite of a large amount of ascites and pleural effusion, no disseminating tumor was detected on contrast-enhanced CT at our hospital, and we recommended that she undergo a diagnostic laparotomy. The laparotomy was negative for carcinomatous peritonitis and a right oophorectomy was performed. The histopathological findings indicated that the ovarian tumor was consistent with metastasis from ascending colon cancer. After the surgery, we initiated chemotherapy with mFOLFOX6+bevacizumab and the symptoms were well controlled. A follow-up CT carried out 11 months after the surgery revealed a left ovarian tumor and increased ascites, and the patient underwent a left oophorectomy. Then, chemotherapy with the same regimen was administered for 12 months, and she did not develop any signs of recurrence for 27 months after the surgery. Ovarian metastasis from colon cancer may occasionally cause pseudo-Meigs syndrome, and it is important to be aware of the usefulness of oophorectomy for the control of ascites and pleural effusion.

  10. Associations between red meat and risks for colon and rectal cancer depend on the type of red meat consumed.

    PubMed

    Egeberg, Rikke; Olsen, Anja; Christensen, Jane; Halkjær, Jytte; Jakobsen, Marianne Uhre; Overvad, Kim; Tjønneland, Anne

    2013-04-01

    Cancer prevention guidelines recommend limiting intake of red meat and avoiding processed meat; however, few studies have been conducted on the effects of specific red meat subtypes on colon cancer or rectal cancer risk. The study aim was to evaluate associations between intake of red meat and its subtypes, processed meat, fish, and poultry and risk for colon cancer or rectal cancer in the Danish Diet, Cancer and Health cohort study. We also evaluated whether fish or poultry should replace red meat intake to prevent colon cancer or rectal cancer. During follow-up (13.4 y), 644 cases of colon cancer and 345 cases of rectal cancer occurred among 53,988 participants. Cox proportional hazards models were used to compute incidence rate ratio (IRRs) and 95% CIs. No associations were found between intake of red meat, processed meat, fish, or poultry and risk for colon cancer or rectal cancer. The risk associated with specific red meat subtypes depended on the animal of origin and cancer subsite; thus, the risk for colon cancer was significantly elevated for higher intake of lamb [IRR(per 5g/d) = 1.07 (95% CI: 1.02-1.13)], whereas the risk for rectal cancer was elevated for higher intake of pork [IRR(per 25g/d) = 1.18 (95% CI: 1.02-1.36)]. Substitution of fish for red meat was associated with a significantly lower risk for colon cancer [IRR(per 25g/d) = 0.89 (95% CI: 0.80-0.99)] but not rectal cancer. Substitution of poultry for red meat did not reduce either risk. This study suggests that the risks for colon cancer and potentially for rectal cancer differ according to the specific red meat subtype consumed.

  11. Aberrant repair of etheno-DNA adducts in leukocytes and colon tissue of colon cancer patients.

    PubMed

    Obtułowicz, Tomasz; Winczura, Alicja; Speina, Elzbieta; Swoboda, Maja; Janik, Justyna; Janowska, Beata; Cieśla, Jarosław M; Kowalczyk, Paweł; Jawien, Arkadiusz; Gackowski, Daniel; Banaszkiewicz, Zbigniew; Krasnodebski, Ireneusz; Chaber, Andrzej; Olinski, Ryszard; Nair, Jagadesaan; Bartsch, Helmut; Douki, Thierry; Cadet, Jean; Tudek, Barbara

    2010-09-15

    To assess the role of lipid peroxidation-induced DNA damage and repair in colon carcinogenesis, the excision rates and levels of 1,N(6)-etheno-2'-deoxyadenosine (epsilondA), 3,N(4)-etheno-2'-deoxycytidine (epsilondC), and 1,N(2)-etheno-2'-deoxyguanosine (1,N(2)-epsilondG) were analyzed in polymorphic blood leukocytes (PBL) and resected colon tissues of 54 colorectal carcinoma (CRC) patients and PBL of 56 healthy individuals. In PBL the excision rates of 1,N(6)-ethenoadenine (epsilonAde) and 3,N(4)-ethenocytosine (epsilonCyt), measured by the nicking of oligodeoxynucleotide duplexes with single lesions, and unexpectedly also the levels of epsilondA and 1,N(2)-epsilondG, measured by LC/MS/MS, were lower in CRC patients than in controls. In contrast the mRNA levels of repair enzymes, alkylpurine- and thymine-DNA glycosylases and abasic site endonuclease (APE1), were higher in PBL of CRC patients than in those of controls, as measured by QPCR. In the target colon tissues epsilonAde and epsilonCyt excision rates were higher, whereas the epsilondA and epsilondC levels in DNA, measured by (32)P-postlabeling, were lower in tumor than in adjacent colon tissue, although a higher mRNA level was observed only for APE1. This suggests that during the onset of carcinogenesis, etheno adduct repair in the colon seems to be under a complex transcriptional and posttranscriptional control, whereby deregulation may act as a driving force for malignancy.

  12. Inhibition of Wnt/β-Catenin Pathway by Dehydrocostus Lactone and Costunolide in Colon Cancer Cells.

    PubMed

    Dong, Guang-Zhi; Shim, Ah-Ram; Hyeon, Jin Seong; Lee, Hwa Jin; Ryu, Jae-Ha

    2015-05-01

    Abnormal activation of β-catenin has been reported in 90% in the sporadic and hereditary colorectal cancer. The suppression of abnormally activated β-catenin is one of the good strategies for chemoprevention and treatment of colorectal cancer. In this study, we have isolated two main compounds from root of Saussurea lappa, dehydrocostus lactone (DCL) and costunolide (CL), and investigated their anti-colorectal cancer activities. DCL and CL suppressed cyclin D1 and survivin through inhibiting nuclear translocation of β-catenin. They also suppressed the nuclear translocation of galectin-3 that is one of the coactivators of β-catenin in SW-480 colon cancer cells. Furthermore, DCL and CL suppressed proliferation and survival of SW-480 colon cancer cells through the induction of cell cycle arrest and cell death. Taken together, DCL and CL from root of S. lappa have anti-colorectal cancer activities through inhibiting Wnt/β-catenin pathway.

  13. PHLPP regulates hexokinase 2-dependent glucose metabolism in colon cancer cells

    PubMed Central

    Xiong, Xiaopeng; Wen, Yang-An; Mitov, Mihail I; C Oaks, Mary; Miyamoto, Shigeki; Gao, Tianyan

    2017-01-01

    Increased glucose metabolism is considered as one of the most important metabolic alterations adapted by cancer cells in order to generate energy as well as high levels of glycolytic intermediates to support rapid proliferation. PH domain leucine-rich repeat protein phosphatase (PHLPP) belongs to a novel family of Ser/Thr protein phosphatases that function as tumor suppressors in various types of human cancer. Here we determined the role of PHLPP in regulating glucose metabolism in colon cancer cells. Knockdown of PHLPP increased the rate of glucose consumption and lactate production, whereas overexpression of PHLPP had the opposite effect. Bioenergetic analysis using Seahorse Extracelluar Flux Analyzer revealed that silencing PHLPP expression induced a glycolytic shift in colon cancer cells. Mechanistically, we found that PHLPP formed a complex with Akt and hexokinase 2 (HK2) in the mitochondrial fraction of colon cancer cells and knockdown of PHLPP enhanced Akt-mediated phosphorylation and mitochondrial localization of HK2. Depletion of HK2 expression or treating cells with Akt and HK2 inhibitors reversed PHLPP loss-induced increase in glycolysis. Furthermore, PHLPP knockdown cells became addicted to glucose as a major energy source in that glucose starvation significantly decreased cancer cell survival. As HK2 is the key enzyme that determines the direction and magnitude of glucose flux, our study identified PHLPP as a novel regulator of glucose metabolism by controlling HK2 activity in colon cancer cells. PMID:28179998

  14. EURECCA consensus conference highlights about colon & rectal cancer multidisciplinary management: the radiology experts review.

    PubMed

    Tudyka, V; Blomqvist, L; Beets-Tan, R G H; Boelens, P G; Valentini, V; van de Velde, C J; Dieguez, A; Brown, G

    2014-04-01

    Some interesting shifts have taken place in the diagnostic approach for detection of colorectal lesions over the past decade. This article accompanies the recent EURECCA consensus group reccomendations for optimal management of colon and rectal cancers. In summary, imaging has a crucial role to play in the diagnosis, staging assessment and follow up of patients with colon and rectal cancer. Recent advances include the use of CT colonography instead of Barium Enema in the diagnosis of colonoic cancer and as an alternative to colonoscopy. Modern mutlidetector CT scanning techniques have also shown improvements in prognostic stratification of patients with colonic cancer and clinical trials are underway testing the selective use of neoadjuvant therapy for imaging identified high risk colon cancers. In rectal cancer, high resolution MRI with a voxel size less or equal to 3 × 1 × 1 mm3 on T2-weighted images has a proven ability to accurately stage patients with rectal cancer. Moreover, preoperative identification of prognostic features allows stratification of patients into different prognostic groups based on assessment of depth of extramural spread, relationship of the tumour edge to the mesorectal fascia (MRF) and extramural venous invasion (EMVI). These poor prognostic features predict an increased risk of local recurrence and/or metastatic disease and should form the basis for preoperative local staging and multidisciplinary preoperative discussion of patient treatment options.

  15. The oncogenic effects of p53-inducible gene 3 (PIG3) in colon cancer cells

    PubMed Central

    Park, Seon-Joo; Kim, Hong Beum; Kim, Jeeho

    2017-01-01

    The p53-inducible gene 3 (PIG3), initially identified as a gene downstream of p53, plays an important role in the apoptotic process triggered by p53-mediated reactive oxygen species (ROS) production. Recently, several studies have suggested that PIG3 may play a role in various types of cancer. However, the functional significance of PIG3 in cancer remains unclear. Here, we found that PIG3 was highly expressed in human colon cancer cell lines compared to normal colonderived fibroblasts. Therefore, we attempted to elucidate the functional role of PIG3 in colon cancer. PIG3 overexpression increases the colony formation, migration and invasion ability of HCT116 colon cancer cells. Conversely, these tumorigenic abilities were significantly decreased in in vitro studies with PIG3 knockdown HCT116 cells. PIG3 knockdown also attenuated the growth of mouse xenograft tumors. These results demonstrate that PIG3 is associated with the tumorigenic potential of cancer cells, both in vitro and in vivo, and could play a key oncogenic role in colon cancer. PMID:28280421

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

    MedlinePlus

    ... Cancer Home What Are the Risk Factors for Colorectal Cancer? Language: English Español (Spanish) Recommend on Facebook Tweet Share Compartir Your risk of getting colorectal cancer increases as you get older. More than 90% ...

  17. Evaluation of tumour-associated antigen (TAA) miniarray in immunodiagnosis of colon cancer.

    PubMed

    Liu, W; Wang, P; Li, Z; Xu, W; Dai, L; Wang, K; Zhang, J

    2009-01-01

    Previous studies demonstrated that cancer sera contain antibodies, which react with a unique group of autologous cellular antigens called tumour-associated antigens (TAAs). This study determines whether a mini-array of multiple TAAs would enhance antibody detection and be a useful approach in colon cancer detection and diagnosis. The mini-array of multiple TAAs was composed of five TAAs including Imp1, p62, Koc, p53 and c-myc full-length recombinant proteins. Enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies against these five TAAs in 46 sera from patients with colon cancer and also 58 sera from normal individuals. Antibody frequency to any individual TAA in colon cancer was variable and ranged from 15.2% to 23.9%. With the successive addition of TAAs to a final total of five antigens, there was a stepwise increase of positive antibody reactions reaching a sensitivity of 60.9% and a specificity of 89.7% in colon cancer. Positive and negative likelihood ratio was 5.91 and 0.43 respectively, which showed that the clinical diagnostic value of parallel assay of five TAAs was high. Positive and negative predictive values were respectively 82.4% and 74.3% indicating that parallel assay of five TAAs raised the diagnostic precision greatly. Agreement rate and Kappa value were 76.9% and 0.52 respectively, which indicated that the observed value of this assay had middle range coincidence with actual value. The data from this study further support our previous hypothesis that detection of autoantibodies for diagnosis of certain type of cancer can be enhanced by using a mini-array of several TAAs as target antigens. In 19 colon cancer sera with carcinoembryonic antigen (CEA) negative, 11 (57.9%) were found to have anti-TAA antibodies. When CEA and anti-TAAs were used together as markers in colon cancer detection, the diagnostic sensitivity could be raised from 60.9% to 82.6%. A customized antigen mini-array using a panel of appropriately selected TAAs can

  18. Trypanosomiasis-Induced Megacolon Illustrates How Myenteric Neurons Modulate the Risk for Colon Cancer in Rats and Humans

    PubMed Central

    Kannen, Vinicius; de Oliveira, Enio C.; Motta, Bruno Zene; Chaguri, Annuar Jose; Brunaldi, Mariângela Ottoboni; Garcia, Sérgio B.

    2015-01-01

    Background Trypanosomiasis induces a remarkable myenteric neuronal degeneration leading to megacolon. Very little is known about the risk for colon cancer in chagasic megacolon patients. To clarify whether chagasic megacolon impacts on colon carcinogenesis, we investigated the risk for colon cancer in Trypanosoma cruzi (T. cruzi) infected patients and rats. Methods Colon samples from T. cruzi-infected and uninfected patients and rats were histopathologically investigated with colon cancer biomarkers. An experimental model for chemical myenteric denervation was also performed to verify the myenteric neuronal effects on colon carcinogenesis. All experiments complied the guidelines and approval of ethical institutional review boards. Results No colon tumors were found in chagasic megacolon samples. A significant myenteric neuronal denervation was observed. Epithelial cell proliferation and hyperplasia were found increased in chagasic megacolon. Analyzing the argyrophilic nucleolar organiser regions within the cryptal bottom revealed reduced risk for colon cancer in Chagas’ megacolon patients. T. cruzi-infected rats showed a significant myenteric neuronal denervation and decreased numbers of colon preneoplastic lesions. In chemical myenteric denervated rats preneoplastic lesions were reduced from the 2nd wk onward, which ensued having the colon myenteric denervation significantly induced. Conclusion/Significance Our data suggest that the trypanosomiasis-related myenteric neuronal degeneration protects the colon tissue from carcinogenic events. Current findings highlight potential mechanisms in tropical diseases and cancer research. PMID:25884710

  19. Cancer-Associated Immune Resistance and Evasion of Immune Surveillance in Colorectal Cancer

    PubMed Central

    Laudanna, Carmelo; Febbraro, Antonio

    2016-01-01

    Data from molecular profiles of tumors and tumor associated cells provide a model in which cancer cells can acquire the capability of avoiding immune surveillance by expressing an immune-like phenotype. Recent works reveal that expression of immune antigens (PDL1, CD47, CD73, CD14, CD68, MAC387, CD163, DAP12, and CD15) by tumor cells “immune resistance,” combined with prometastatic function of nonmalignant infiltrating cells, may represent a strategy to overcome the rate-limiting steps of metastatic cascade through (a) enhanced interactions with protumorigenic myeloid cells and escape from T-dependent immune response mediated by CD8+ and natural killer (NK) cells; (b) production of immune mediators that establish a local and systemic tumor-supportive environment (premetastatic niche); (c) ability to survive either in the peripheral blood as circulating tumor cells (CTCs) or at the metastatic site forming a cooperative prometastatic loop with foreign “myeloid” cells, macrophages, and neutrophils, respectively. The development of cancer-specific “immune resistance” can be orchestrated either by cooperation with tumor microenvironment or by successive rounds of genetic/epigenetic changes. Recognition of the applicability of this model may provide effective therapeutic avenues for complete elimination of immune-resistant metastatic cells and for enhanced antitumor immunity as part of a combinatorial strategy. PMID:27006653

  20. Cancer-Associated Immune Resistance and Evasion of Immune Surveillance in Colorectal Cancer.

    PubMed

    Parcesepe, Pietro; Giordano, Guido; Laudanna, Carmelo; Febbraro, Antonio; Pancione, Massimo

    2016-01-01

    Data from molecular profiles of tumors and tumor associated cells provide a model in which cancer cells can acquire the capability of avoiding immune surveillance by expressing an immune-like phenotype. Recent works reveal that expression of immune antigens (PDL1, CD47, CD73, CD14, CD68, MAC387, CD163, DAP12, and CD15) by tumor cells "immune resistance," combined with prometastatic function of nonmalignant infiltrating cells, may represent a strategy to overcome the rate-limiting steps of metastatic cascade through (a) enhanced interactions with protumorigenic myeloid cells and escape from T-dependent immune response mediated by CD8+ and natural killer (NK) cells; (b) production of immune mediators that establish a local and systemic tumor-supportive environment (premetastatic niche); (c) ability to survive either in the peripheral blood as circulating tumor cells (CTCs) or at the metastatic site forming a cooperative prometastatic loop with foreign "myeloid" cells, macrophages, and neutrophils, respectively. The development of cancer-specific "immune resistance" can be orchestrated either by cooperation with tumor microenvironment or by successive rounds of genetic/epigenetic changes. Recognition of the applicability of this model may provide effective therapeutic avenues for complete elimination of immune-resistant metastatic cells and for enhanced antitumor immunity as part of a combinatorial strategy.

  1. Optical diagnosis of colon and cervical cancer by support vector machine

    NASA Astrophysics Data System (ADS)

    Mukhopadhyay, Sabyasachi; Kurmi, Indrajit; Dey, Rajib; Das, Nandan K.; Pradhan, Sanjay; Pradhan, Asima; Ghosh, Nirmalya; Panigrahi, Prasanta K.; Mohanty, Samarendra

    2016-05-01

    A probabilistic robust diagnostic algorithm is very much essential for successful cancer diagnosis by optical spectroscopy. We report here support vector machine (SVM) classification to better discriminate the colon and cervical cancer tissues from normal tissues based on elastic scattering spectroscopy. The efficacy of SVM based classification with different kernel has been tested on multifractal parameters like Hurst exponent, singularity spectrum width in order to classify the cancer tissues.

  2. DAC can restore expression of NALP1 to suppress tumor growth in colon cancer.

    PubMed

    Chen, C; Wang, B; Sun, J; Na, H; Chen, Z; Zhu, Z; Yan, L; Ren, S; Zuo, Y

    2015-01-22

    Despite recent progress in the identification of genetic and molecular alternations in colorectal carcinoma, the precise molecular pathogenesis remains unclear. NALP1 (nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 1) is a member of the nucleotide-binding oligomerization domain-like receptor family of proteins that are key organization proteins in the inflammasome. It is reported that NALP1 plays a central role in cell apoptosis, pyroptosis, inflammatory reactions and autoimmune diseases. DAC (5-aza-2-deoxycytidine) is an antitumor drug useful to lung cancer, myelodysplastic disorders, myelodysplasia and acute myeloid leukemia. In this study, we examined the expression of NALP1 in human normal and cancerous colon tissues using tissue microarray, western blot and quantitative real-time PCR and we measured the expression of NALP1 in three kinds of colon cancer cell lines and animal models before and after treatment with DAC. Furthermore, we examined the treatment effects of DAC on colon cancer in our animal model. Our data indicate that NALP1 is expressed low in human colorectal tumoral tissues relative to paratumoral tissues and was associated with the survival and tumor metastasis of patients. The expression of NALP1 increased after treatment with DAC both in vitro and in vivo. Furthermore, DAC suppressed the growth of colon cancer and increased lifespan in mouse model. Therefore, we conclude that NALP1 is expressed low in colon cancer and associated with the survival and tumor metastasis of patients, and treatment with DAC can restore NALP1 levels to suppress the growth of colon cancer.

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

    PubMed

    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.

  4. Pulmonary metastatic microangiopathy of colon cancer presenting as a "tree in bud" pattern.

    PubMed

    Bosmans, S; Weynand, B; Coche, E

    2008-01-01

    The authors report an unusual case of a "tree in bud" pattern of vascular origin caused by colon cancer metastases. A 60-year-old man presented for routine follow-up of a colon tumour resected surgically 15 years previously. Clinical examination, laboratory tests, including carcino-embryonic antigen and inflammatory parameters, and chest radiograph were normal. Multislice CT of the lungs revealed the presence of several "tree in bud" opacities. The connection to the pulmonary arteries was well depicted by reformatted maximal intensity projection images. Biopsy of some of the nodules was characterized by mucinous material and neoplastic cells within the small vessels, consistent with metastases from the known colon adenocarcinoma.

  5. The anti-cancer effects of poi (Colocasia esculenta) on colonic adenocarcinoma cells In vitro.

    PubMed

    Brown, Amy C; Reitzenstein, Jonathan E; Liu, Jessie; Jadus, Martin R

    2005-09-01

    Hawaiians tend to have lower incidence rates of colorectal cancer and it was hypothesized that this may be due to ethnic differences in diet, specifically, their consumption of poi, a starchy paste made from the taro (Colocasia esulenta L.) plant corm. Soluble extracts of poi were incubated at 100 mg/mL in vitro for antiproliferative activity against the rat YYT colon cancer cell line. (3)H-thymidine incorporation studies were conducted to demonstrate that the poi inhibited the proliferation of these cancer cells in a dose-dependent manner. The greatest suppression of YYT colon cancer growth occurred when 25% concentration was used. When poi was incubated with the YYT cells after 2 days, the YYT cells underwent apoptotic changes as evidenced by a positive terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) stain. Poi enhanced the proliferation of normal mouse splenocyte control cells, suggesting that poi is not simply toxic to all cells but even has a positive immunostimulatory role. By flow cytometry, T cells (CD4+ and CD8+) were predominantly activated by the poi. Although numerous factors can contribute to the risk of colon cancer, perhaps poi consumption may contribute to the lower colon cancer rates among Hawaiians by two distinct mechanisms. First, by inducing apoptosis within colon cancer cells; second, by non-specifically activating lymphocytes, which in turn can lyse cancerous cells. Our results suggest for the first time that poi may have novel tumor specific anti-cancer activities and future research is suggested with animal studies and human clinical trials.

  6. Protective links between vitamin D, inflammatory bowel disease and colon cancer.

    PubMed

    Meeker, Stacey; Seamons, Audrey; Maggio-Price, Lillian; Paik, Jisun

    2016-01-21

    Vitamin D deficiency has been associated with a wide range of diseases and multiple forms of cancer including breast, colon, and prostate cancers. Relatively recent work has demonstrated vitamin D to be critical in immune function and therefore important in inflammatory diseases such as inflammatory bowel disease (IBD). Because vitamin D deficiency or insufficiency is increasingly prevalent around the world, with an estimated 30%-50% of children and adults at risk for vitamin D deficiency worldwide, it could have a significant impact on IBD. Epidemiologic studies suggest that low serum vitamin D levels are a risk factor for IBD and colon cancer, and vitamin D supplementation is associated with decreased colitis disease activity and/or alleviated symptoms. Patients diagnosed with IBD have a higher incidence of colorectal cancer than the general population, which supports the notion that inflammation plays a key role in cancer development and underscores the importance of understanding how vitamin D influences inflammation and its cancer-promoting effects. In addition to human epidemiological data, studies utilizing mouse models of colitis have shown that vitamin D is beneficial in preventing or ameliorating inflammation and clinical disease. The precise role of vitamin D on colitis is unknown; however, vitamin D regulates immune cell trafficking and differentiation, gut barrier function and antimicrobial peptide synthesis, all of which may be protective from IBD and colon cancer. Here we focus on effects of vitamin D on inflammation and inflammation-associated colon cancer and discuss the potential use of vitamin D for protection and treatment of IBD and colon cancer.

  7. Laparoscopic surgery for colon cancer: a review of the fascial composition of the abdominal cavity.

    PubMed

    Mike, Makio; Kano, Nobuyasu

    2015-02-01

    Laparoscopic surgery has generally been performed for digestive diseases. Many patients with colon cancer undergo laparoscopic procedures. The outcomes of laparoscopic colectomy and open colectomy are the same in terms of the long-time survival. It is important to dissect the embryological plane to harvest the lymph nodes and to avoid bleeding during colon cancer surgery. To date, descriptions of the anatomy of the fascial composition have mainly involved observations unrelated to fundamental embryological concepts, causing confusion regarding the explanations of the surgical procedures, with various vocabularies used without definitions. We therefore examined the fascia of the abdominal space using a fascia concept based on clinical anatomy and embryology. Mobilization of the bilateral sides of the colon involves dissection between the fusion fascia of Toldt and the deep subperitoneal fascia. It is important to understand that the right fusion fascia of Toldt is divided into the posterior pancreatic fascia of Treitz dorsally and the anterior pancreatic fascia ventrally at the second portion of the duodenum. A comprehensive understanding of fascia composition between the stomach and transverse colon is necessary for dissecting the splenic flexure of the colon. As a result of these considerations of the fascia, more accurate surgical procedures can be performed for the excision of colon cancer.

  8. Colonization by Candida in children with cancer, children with cystic fibrosis, and healthy controls.

    PubMed

    Gammelsrud, K W; Sandven, P; Høiby, E A; Sandvik, L; Brandtzaeg, P; Gaustad, P

    2011-12-01

    A longitudinal, prospective study was conducted intermittently in Norway, from 1999 to 2008, to investigate the Candida colonization rates and species distributions in the tonsillopharyngeal and faecal flora in: (i) children with cancer; (ii) children with cystic fibrosis (CF); and (iii) healthy children. The effect of antibiotic treatment on Candida colonization was also studied, and we looked for changes in antifungal susceptibility over time within each child and between the different groups of children. In total, 566 tonsillopharyngeal swabs and 545 faecal samples were collected from 45 children with cancer, 37 children with CF, and 71 healthy, age-matched controls. The overall colonization rate with Candida was not significantly higher in the two groups of children undergoing extensive treatment with broad-spectrum antibiotics than in healthy controls. Approximately one-third of the cancer patients had a total lack of Candida colonization or had only one Candida-positive sample, despite multiple samples being taken, treatment with broad-spectrum antibiotics, long hospital stays, and periods with neutropenia. Children with CF had the highest prevalence of Candida albicans. Amoxycillin, azithromycin, third-generation cephalosporins and oral vancomycin resulted in a significantly increased Candida colonization rate. Phenoxymethylpenicillin, second-generation cephalosporins, metronidazole, trimethoprim-sulphamethoxazole, ciprofloxacin, penicillinase-resistant penicillins and inhaled tobramycin or colistin showed minimal effects on the Candida colonization rate. We found no evidence of development of antifungal resistance over time.

  9. PPARδ deficiency disrupts hypoxia-mediated tumorigenic potential of colon cancer cells.

    PubMed

    Jeong, Eunshil; Koo, Jung Eun; Yeon, Sang Hyeon; Kwak, Mi-Kyoung; Hwang, Daniel H; Lee, Joo Young

    2014-11-01

    Peroxisome proliferator-activated receptor (PPAR) δ is highly expressed in colon epithelial cells and closely linked to colon carcinogenesis. However, the role of PPARδ in colon cancer cells in a hypoxic tumor microenvironment is not fully understood. We found that expression of the tumor-promoting cytokines, IL-8 and VEGF, induced by hypoxia (<1% O2) and deferoxamine (a hypoxia mimetic) was significantly attenuated in PPARδ-deficient HCT116 colon cancer cells. Consequently, PPARδ-knockout colon cancer cells exposed to hypoxia and deferoxamine failed to stimulate endothelial cell vascularization and macrophage migration/proliferation, whereas wild-type cells were able to induce angiogenesis and macrophage activation in response to hypoxic stress. Hypoxic stress induced transcriptional activation of PPARδ, but not its protein expression, in HCT116 cells. Exogenous expression of p300 potentiated deferoxamine-induced PPARδ transactivation, while siRNA knockdown of p300 abolished hypoxia- and deferoxamine-induced PPARδ transactivation. PPARδ associated with p300 upon hypoxic stress as demonstrated by coimmunoprecipitation studies. PI3K inhibitors or siRNA knockdown of Akt suppressed the PPARδ transactivation induced by hypoxia and deferoxamine in HCT116 cells, leading to decreased expression of IL-8 and VEGF. Collectively, these results reveal that PPARδ is required for hypoxic stress-mediated cytokine expression in colon cancer cells, resulting in promotion of angiogenesis, macrophage recruitment, and macrophage proliferation in the tumor microenvironment. p300 and the PI3K/Akt pathway play a role in the regulation of PPARδ transactivation induced by hypoxic stress. Our results demonstrate the positive crosstalk between PPARδ in tumor cells and the hypoxic tumor microenvironment and provide potential therapeutic targets for colon cancer.

  10. Genomic profiling of stage II and III colon cancers reveals APC mutations to be associated with survival in stage III colon cancer patients

    PubMed Central

    van den Broek, Evert; Krijgsman, Oscar; Sie, Daoud; Tijssen, Marianne; Mongera, Sandra; van de Wiel, Mark A.; Th. Belt, Eric J.; den Uil, Sjoerd H.; Bril, Herman; Stockmann, Hein B.A.C.; Ylstra, Bauke; Carvalho, Beatriz; Meijer, Gerrit A.; Fijneman, Remond J.A.

    2016-01-01

    Tumor profiling of DNA alterations, i.e. gene point mutations, somatic copy number aberrations (CNAs) and structural variants (SVs), improves insight into the molecular pathology of cancer and clinical outcome. Here, associations between genomic aberrations and disease recurrence in stage II and III colon cancers were investigated. A series of 114 stage II and III microsatellite stable colon cancer samples were analyzed by high-resolution array-comparative genomic hybridization (array-CGH) to detect CNAs and CNA-associated chromosomal breakpoints (SVs). For 60 of these samples mutation status of APC, TP53, KRAS, PIK3CA, FBXW7, SMAD4, BRAF and NRAS was determined using targeted massive parallel sequencing. Loss of chromosome 18q12.1-18q12.2 occurred more frequently in tumors that relapsed than in relapse-free tumors (p < 0.001; FDR = 0.13). In total, 267 genes were recurrently affected by SVs (FDR < 0.1). CNAs and SVs were not associated with disease-free survival (DFS). Mutations in APC and TP53 were associated with increased CNAs. APC mutations were associated with poor prognosis in (5-fluorouracil treated) stage III colon cancers (p = 0.005; HR = 4.1), an effect that was further enhanced by mutations in MAPK pathway (KRAS, NRAS, BRAF) genes. We conclude that among multiple genomic alterations in CRC, strongest associations with clinical outcome were observed for common mutations in APC. PMID:27729614

  11. Metachronous adenoma on ileorectal anastomosis suture line and submucosal deep invasive cancer suspected of rapid growth in rectal remnant following long-term interval after curative surgery for advanced colon cancer.

    PubMed

    Uraoka, Toshio; Horii, Joichiro; Goto, Osamu; Shimoda, Masayuki; Yahagi, Naohisa

    2013-05-01

    There is general agreement as to the value of postoperative surveillance and the effectiveness of colonoscopy in the early detection of metachronous colorectal lesions. In the present case, a 56-year-old woman with no family history of colon cancer underwent surveillance colonoscopy in which a metachronous flat adenoma was detected following an interval of 23 years after a colectomy and 20 years subsequent to treatment for uterine cancer. A second metachronous flat lesion histopathologically determined to be a submucosal (sm) deep invasive cancer with lymphovascular involvement was detected 12 months later. This second metachronous lesion was suspected of having developed rapidly in the rectal remnant accounting for its sm deep invasion. The findings of this case suggest colonoscopy surveillance guidelines proposed for individuals at high risk should be evaluated based on cancer history and an analysis of possible mismatch repair gene mutations. In addition, the first metachronous lesion was located directly on the suture line of the anastomosis. Endoscopic submucosal dissection (ESD) was indicated despite severe fibrosis into the sm layer. This case also demonstrates the successful use of improved ESD instruments, sm injection agents and technique refinements in the treatment of a technically difficult lesion with a high risk of complications.

  12. Ovine intestinal adenocarcinomas: histologic and phenotypic comparison with human colon cancer.

    PubMed

    Munday, John S; Brennan, Moira M; Jaber, Azhar M; Kiupel, Matti

    2006-04-01

    Approximately 7% of old, unthrifty sheep (Ovis aries) in New Zealand have intestinal adenocarcinomas. To investigate whether these sheep might be used as a model of human colonic neoplasia, the biologic behavior and histologic appearance of ovine intestinal adenocarcinomas were compared with those reported for human colonic adenocarcinomas. We collected 50 intestinal tracts with grossly visible intestinal neoplasia from slaughtered sheep. Neoplasms were assessed using World Health Organization guidelines for assessment of human colonic adenocarcinomas. All ovine adenocarcinomas developed in the small intestine. In contrast, only 4% of human intestinal tumors develop at this location, whereas the majority develop in the colon. A visible polyp is present within 89% of human colonic adenocarcinomas, whereas polyps were present in only 46% of the ovine neoplasms. Intestinal wall infiltration by the neoplastic cells and rates of lymph node (84% in sheep; 61% in humans) and distant (52% in sheep; 17% in humans) metastases were comparable between ovine and human adenocarcinomas. However, ovine adenocarcinomas developed more peritoneal and fewer hepatic metastases than human adenocarcinomas. Histologic grading of ovine tumors revealed cell differentiation similar to that reported within human colonic adenocarcinomas. In conclusion, ovine intestinal adenocarcinomas, like human colonic adenocarcinomas, typically arise spontaneously and consistently develop widespread metastases. In addition, tumors appear histologically similar between these species. Therefore, sheep may provide a model of advanced human colonic cancer, possibly allowing evaluation of novel therapeutics and surgical procedures.

  13. Differential regulation of EGFR-MAPK signaling by deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) in colon cancer.

    PubMed

    Centuori, Sara M; Martinez, Jesse D

    2014-10-01

    A high-fat diet coincides with increased levels of bile acids. This increase in bile acids, particularly deoxycholic acid (DCA), has been strongly associated with the development of colon cancer. Conversely, ursodeoxycholic acid (UDCA) may have chemopreventive properties. Although structurally similar, DCA and UDCA present different biological and pathological effects in colon cancer progression. The differential regulation of cancer by these two bile acids is not yet fully understood. However, one possible explanation for their diverging effects is their ability to differentially regulate signaling pathways involved in the multistep progression of colon cancer, such as the epidermal growth factor receptor (EGFR)-mitogen-activated protein kinase (MAPK) pathway. This review will examine the biological effects of DCA and UDCA on colon cancer development, as well as the diverging effects of these bile acids on the oncogenic signaling pathways that play a role in colon cancer development, with a particular emphasis on bile acid regulation of the EGFR-MAPK pathway.

  14. Gut Microbiota Imbalance and Base Excision Repair Dynamics in Colon Cancer

    PubMed Central

    Ray, Debolina; Kidane, Dawit

    2016-01-01

    Gut microbiota are required for host nutrition, energy balance, and regulating immune homeostasis, however, in some cases, this mutually beneficial relationship becomes twisted (dysbiosis), and the gut flora can incite pathological disorders including colon cancer. Microbial dysbiosis promotes the release of bacterial genotoxins, metabolites, and causes chronic inflammation, which promote oxidative DNA damage. Oxidized DNA base lesions are removed by base excision repair (BER), however, the role of this altered function of BER, as well as microbiota-mediated genomic instability and colon cancer development, is still poorly understood. In this review article, we will discuss how dysbiotic microbiota induce DNA damage, its impact on base excision repair capacity, the potential link of host BER gene polymorphism, and the risk of dysbiotic microbiota mediated genomic instability and colon cancer. PMID:27471558

  15. γδ T cells as a potential tool in colon cancer immunotherapy.

    PubMed

    Ramutton, Thiranut; Buccheri, Simona; Dieli, Francesco; Todaro, Matilde; Stassi, Giorgio; Meraviglia, Serena

    2014-01-01

    γδ T cells are capable of recognizing tumor cells and exert potent cellular cytotoxicity against a large range of tumors, including colon cancer. However, tumors utilize numerous strategies to escape recognition or killing by patrolling γδ T cells, such a downregulation of NKG2D ligands, MICA/B and ULBPs. Therefore, the combined upregulation of T-cell receptorand NKG2D ligands on tumor cells and induction of NKG2D expression on γδ T cells may greatly enhance tumor killing and unlock the functions of γδ T cells. Here, we briefly review current data on the mechanisms of γδ T-cell recognition and killing of colon cancer cells and propose that γδ T cells may represent a promising target for the design of novel and highly innovative immunotherapy in patients with colon cancer.

  16. Liver X receptor β activation induces pyroptosis of human and murine colon cancer cells

    PubMed Central

    Derangère, V; Chevriaux, A; Courtaut, F; Bruchard, M; Berger, H; Chalmin, F; Causse, S Z; Limagne, E; Végran, F; Ladoire, S; Simon, B; Boireau, W; Hichami, A; Apetoh, L; Mignot, G; Ghiringhelli, F; Rébé, C

    2014-01-01

    Liver X receptors (LXRs) have been proposed to have some anticancer properties, through molecular mechanisms that remain elusive. Here we report for the first time that LXR ligands induce caspase-1-dependent cell death of colon cancer cells. Caspase-1 activation requires Nod-like-receptor pyrin domain containing 3 (NLRP3) inflammasome and ATP-mediated P2 × 7 receptor activation. Surprisingly, LXRβ is mainly located in the cytoplasm and has a non-genomic role by interacting with pannexin 1 leading to ATP secretion. Finally, LXR ligands have an antitumoral effect in a mouse colon cancer model, dependent on the presence of LXRβ, pannexin 1, NLRP3 and caspase-1 within the tumor cells. Our results demonstrate that LXRβ, through pannexin 1 interaction, can specifically induce caspase-1-dependent colon cancer cell death by pyroptosis. PMID:25124554

  17. Epigenetic silencing of glutaminase 2 in human liver and colon cancers

    PubMed Central

    2013-01-01

    Background Glutaminase 2 (Gls2) is a p53 target gene and is known to play an important role in energy metabolism. Gls2 has been reported to be downregulated in human hepatocellular carcinomas (HCC). However, the underlying mechanism responsible for its downregulation is still unclear. Here, we investigated Gls2 expression and its promoter methylation status in human liver and colon cancers. Methods mRNA expression of Gls2 was determined in human liver and colon cancer cell lines and HCC tissues by real-time PCR and promoter methylation was analyzed by methylation-specific PCR (MSP) and validated by bisulfite genome sequencing (BGS). Cell growth was determined by colony formation assay and MTS assay. Statistical analysis was performed by Wilcoxon matched-pairs test or non-parametric t test. Results First, we observed reduced Gls2 mRNA level in a selected group of liver and colon cancer cell lines and in the cancerous tissues from 20 HCC and 5 human colon cancer patients in comparison to their non-cancerous counter parts. Importantly, the lower level of Gls2 in cancer cells was closely correlated to its promoter hypermethylation; and chemical demethylation treatment with 5-aza-2′-deoxycytidine (Aza) increased Gls2 mRNA level in both liver and colon cancer cells, indicating that direct epigenetic silencing suppressed Gls2 expression by methylation. Next, we further examined this correlation in human HCC tissues, and 60% of primary liver tumor tissues had higher DNA methylation levels when compared with adjacent non-tumor tissues. Detailed methylation analysis of 23 CpG sites at a 300-bp promoter region by bisulfite genomic sequencing confirmed its methylation. Finally, we examined the biological function of Gls2 and found that restoring Gls2 expression in cancer cells significantly inhibited cancer cell growth and colony formation ability through induction of cell cycle arrest. Conclusions We provide evidence showing that epigenetic silencing of Gls2 via promoter

  18. Colon Cancer Tumorigenesis Initiated by the H1047R Mutant PI3K

    PubMed Central

    Yueh, Alexander E.; Payne, Susan N.; Leystra, Alyssa A.; Van De Hey, Dana R.; Foley, Tyler M.; Pasch, Cheri A.; Clipson, Linda; Matkowskyj, Kristina A.; Deming, Dustin A.

    2016-01-01

    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. PMID:26863299

  19. Isothiocyanate analogs targeting CD44 receptor as an effective strategy against colon cancer

    PubMed Central

    Misra, Suniti; Vyas, Alok; O’Brien, Paul; Markwald, Roger R.; Khetmalas, Madhukar; Hascall, Vincent C.; McCarthy, James B.; Karamanos, Nikos K.; Tammi, Markku I.; Tammi, Raija H.; Prestwitch, Glenn D.

    2014-01-01

    Inflammatory pathway plays an important role in tumor cell progression of colorectal cancers. Although colon cancer is considered as one of the leading causes of death worldwide, very few drugs are available for its effective treatment. Many studies have examined the effects of specific COX-2 and 5-LOX inhibitors on human colorectal cancer, but the role of isothiocyanates (ITSCs) as COX–LOX dual inhibitors engaged in hyaluronan–CD44 interaction has not been studied. In the present work, we report series of ITSC analogs incorporating bioisosteric thiosemicarbazone moiety. These inhibitors are effective against panel of human colon cancer cell lines including COX-2 positive HCA-7, HT-29 cells lines, and hyaluronan synthase-2 (Has2) enzyme over-expressing transformed intestinal epithelial Apc10.1Has2 cells. Specifically, our findings indicate that HA-CD44v6-mediated COX-2/5-LOX signaling mediate survivin production, which in turn, supports anti-apoptosis and chemo-resistance leading to colon cancer cell survival. The over-expression of CD44v6shRNA as well as ITSC treatment significantly decreases the survival of colon cancer cells. The present results thus offer an opportunity to evolve potent inhibitors of HA synthesis and CD44v6 pathway and thus underscoring the importance of the ITSC analogs as chemopreventive agents for targeting HA/CD44v6 pathway. PMID:25013352

  20. Unusually large colon cancer cutaneous and subcutaneous metastases occurring in resection scars.

    PubMed

    Alexandrescu, Doru T; Vaillant, Juan; Yahr, Laura J; Kelemen, Pond; Wiernik, Peter H

    2005-08-01

    Development of cutaneous metastases from colon cancer is a rare event, usually occurring in the setting of diffusely-disseminated disease and commonly carrying a dismal prognosis. Cutaneous and subcutaneous metastases in surgical scars occur extremely rarely, with only a few cases reported. We describe two cases of cutaneous metastases from colon cancer. A 62-year-old woman developed an 11-cm midline abdominal mass that slowly grew on the skin surface. The mass occurred at the scar site of her previous surgery performed 5 years prior for resection of a colon adenocarcinoma. A 46-year-old male presented with a subcutaneous 4.5-cm nodule in midline-abdominal scar, 3 years after resection of the primary colon cancer. These cases illustrate the pathological features and natural history of cutaneous metastases observed until the tumors have reached a very large size. Particular features of cutaneous scar metastases from colon cancer observed in our cases are a superficial pattern of spread, strong positivity for EGFR, low serum carcinoembrionic antigen, and long survival of the patients, possibly contributed to by the use of chemotherapy.

  1. beta-Catenin regulates vascular endothelial growth factor expression in colon cancer.

    PubMed

    Easwaran, Vijay; Lee, Sang H; Inge, Landon; Guo, Lida; Goldbeck, Cheryl; Garrett, Evelyn; Wiesmann, Marion; Garcia, Pablo D; Fuller, John H; Chan, Vivien; Randazzo, Filippo; Gundel, Robert; Warren, Robert S; Escobedo, Jaime; Aukerman, Sharon L; Taylor, Robert N; Fantl, Wendy J

    2003-06-15

    To evaluate whether beta-catenin signaling has a role in the regulation of angiogenesis in colon cancer, a series of angiogenesis-related gene promoters was analyzed for beta-catenin/TCF binding sites. Strikingly, the gene promoter of human vascular endothelial growth factor (VEGF, or VEGF-A) contains seven consensus binding sites for beta-catenin/TCF. Analysis of laser capture microdissected human colon cancer tissue indicated a direct correlation between up-regulation of VEGF-A expression and adenomatous polyposis coli (APC) mutational status (activation of beta-catenin signaling) in primary tumors. In metastases, this correlation was not observed. Analysis by immunohistochemistry of intestinal polyps in mice heterozygous for the multiple intestinal neoplasia gene (Min/+) at 5 months revealed an increase and redistribution of VEGF-A in proximity to those cells expressing nuclear beta-catenin with a corresponding increase in vessel density. Transfection of normal colon epithelial cells with activated beta-catenin up-regulated levels of VEGF-A mRNA and protein by 250-300%. When colon cancer cells with elevated beta-catenin levels were treated with beta-catenin antisense oligodeoxynucleotides, VEGF-A expression was reduced by more than 50%. Taken together, our observations indicate a close link between beta-catenin signaling and the regulation of VEGF-A expression in colon cancer.

  2. Cholera-toxin suppresses carcinogenesis in a mouse model of inflammation-driven sporadic colon cancer.

    PubMed

    Doulberis, Michael; Angelopoulou, Katerina; Kaldrymidou, Eleni; Tsingotjidou, Anastasia; Abas, Zaphiris; Erdman, Suzan E; Poutahidis, Theofilos

    2015-02-01

    Human studies and clues from animal models have provided important links between gastrointestinal (GI) tract bacteria and colon cancer. Gut microbiota antigenic stimuli play an important role in shaping the intestinal immune responses. Therefore, especially in the case of inflammation-associated colon cancer, gut bacteria antigens may affect tumorigenesis. The present study aimed to investigate the effects of the oral administration of a bacterial product with known immunomodulatory properties on inflammation-driven colorectal neoplasmatogenesis. For that, we used cholera-toxin and a well-established mouse model of colon cancer in which neoplasia is initiated by a single dose of the genotoxic agent azoxymethane (AOM) and subsequently promoted by inflammation caused by the colitogenic substance dextran sodium sulfate (DSS). We found that a single, low, non-pathogenic dose of CT, given orally at the beginning of each DSS treatment cycle downregulated neutrophils and upregulated regulatory T-cells and IL-10 in the colonic mucosa. The CT-induced disruption of the tumor-promoting character of DSS-induced inflammation led to the reduction of the AOM-initiated colonic polypoidogenesis. This result adds value to the emerging notion that certain GI tract bacteria or their products affect the immune system and render the microenvironment of preneoplastic lesions less favorable for promoting their evolution to cancer.

  3. Contribution of Soft Substrates to Malignancy and Tumor Suppression during Colon Cancer Cell Division

    PubMed Central

    Rabineau, Morgane; Kocgozlu, Leyla; Dujardin, Denis; Senger, Bernard; Haikel, Youssef; Voegel, Jean-Claude; Freund, Jean-Noel; Schaaf, Pierre; Lavalle, Philippe; Vautier, Dominique

    2013-01-01

    In colon cancer, a highly aggressive disease, progression through the malignant sequence is accompanied by increasingly numerous chromosomal rearrangements. To colonize target organs, invasive cells cross several tissues of various elastic moduli. Whether soft tissue increases malignancy or in contrast limits invasive colon cell spreading remains an open question. Using polyelectrolyte multilayer films mimicking microenvironments of various elastic moduli, we revealed that human SW480 colon cancer cells displayed increasing frequency in chromosomal segregation abnormalities when cultured on substrates with decreasing stiffness. Our results show that, although decreasing stiffness correlates with increased cell lethality, a significant proportion of SW480 cancer cells did escape from the very soft substrates, even when bearing abnormal chromosome segregation, achieve mitosis and undergo a new cycle of replication in contrast to human colonic HCoEpiC cells which died on soft substrates. This observation opens the possibility that the ability of cancer cells to overcome defects in chromosome segregation on very soft substrates could contribute to increasing chromosomal rearrangements and tumor cell aggressiveness. PMID:24167628

  4. Colorectal cancer surveillance in patients with inflammatory bowel disease: What is new?

    PubMed Central

    Guagnozzi, Danila; Lucendo, Alfredo J

    2012-01-01

    Several studies assessing the incidence of colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients have found an increased risk globally estimated to be 2 to 5 times higher than for the general population of the same age group. The real magnitude of this risk, however, is still open to debate. Research is currently being carried out on several risk and protective factors for CRC that have recently been identified in IBD patients. A deeper understanding of these factors could help stratify patient risk and aid specialists in choosing which surveillance program is most efficient. There are several guidelines for choosing the correct surveillance program for IBD patients; many present common characteristics with various distinctions. Current recommendations are far from perfect and have important limitations such as the fact that their efficiency has not been demonstrated through randomized controlled trials, the limited number of biopsies performed in daily endoscopic practice, and the difficulty in establishing the correct time to begin a given surveillance program and maintain a schedule of surveillance. That being said, new endoscopic technologies should help by replacing random biopsy protocols with targeted biopsies in IBD patients, thereby improving the efficiency of surveillance programs. However, further studies are needed to evaluate the cost-effectiveness of introducing these techniques into daily endoscopic practice. PMID:22523611

  5. Technique of sentinel lymph node biopsy and lymphatic mapping during laparoscopic colon resection for cancer

    PubMed Central

    Bianchi, PP; Andreoni, B; Rottoli, M; Celotti, S; Chiappa, A; Montorsi, M

    2007-01-01

    Background: The utility of lymph node mapping to improve staging in colon cancer is still under evaluation. Laparoscopic colectomy for colon cancer has been validated in multi-centric trials. This study assessed the feasibility and technical aspects of lymph node mapping in laparoscopic colectomy for colon cancer. Methods: A total of 42 patients with histologically proven colon cancer were studied from January 2006 to September 2007. Exclusion criteria were: advanced disease (clinical stage III), rectal cancer, previous colon resection and contraindication to laparoscopy. Lymph-nodal status was assessed preoperatively by computed tomography (CT) scan and intra-operatively with the aid of laparoscopic ultrasound. Before resection, 2–3 ml of Patent Blue V dye was injected sub-serosally around the tumour. Coloured lymph nodes were marked as sentinel (SN) with metal clips or suture and laparoscopic colectomy with lymphadenectomy completed as normal. In case of failure of the intra-operative procedure, an ex vivo SN biopsy was performed on the colectomy specimen after resection. Results: A total number of 904 lymph nodes were examined, with a median number of 22 lymph nodes harvested per patient. The SN detection rate was 100%, an ex vivo lymph node mapping was necessary in four patients. Eleven (26.2%) patients had lymph-nodal metastases and in five (45.5%) of these patients, SN was the only positive lymph node. There were two (18.2%) false-negative SN. In three cases (7.1%) with aberrant lymphatic drainage, lymphadenectomy was extended. The accuracy of SN mapping was 95.2% and negative predictive value was 93.9%. Conclusions: Laparoscopic lymphatic mapping and SN removal is feasible in laparoscopic colectomy for colon cancer. The ex vivo technique is useful as a salvage technique in case of failure of the intra-operative procedure. Prospective studies are justified to determine the real accuracy and false-negative rate of the technique. PMID:22275957

  6. Role of connexins in metastatic breast cancer and melanoma brain colonization.

    PubMed

    Stoletov, Konstantin; Strnadel, Jan; Zardouzian, Erin; Momiyama, Masashi; Park, Frederick D; Kelber, Jonathan A; Pizzo, Donald P; Hoffman, Robert; VandenBerg, Scott R; Klemke, Richard L

    2013-02-15

    Breast cancer and melanoma cells commonly metastasize to the brain using homing mechanisms that are poorly understood. Cancer patients with brain metastases display poor prognosis and survival due to the lack of effective therapeutics and treatment strategies. Recent work using intravital microscopy and preclinical animal models indicates that metastatic cells colonize the brain, specifically in close contact with the existing brain vasculature. However, it is not known how contact with the vascular niche promotes microtumor formation. Here, we investigate the role of connexins in mediating early events in brain colonization using transparent zebrafish and chicken embryo models of brain metastasis. We provide evidence that breast cancer and melanoma cells utilize connexin gap junction proteins (Cx43, Cx26) to initiate brain metastatic lesion formation in association with the vasculature. RNAi depletion of connexins or pharmacological blocking of connexin-mediated cell-cell communication with carbenoxolone inhibited brain colonization by blocking tumor cell extravasation and blood vessel co-option. Activation of the metastatic gene twist in breast cancer cells increased Cx43 protein expression and gap junction communication, leading to increased extravasation, blood vessel co-option and brain colonization. Conversely, inhibiting twist activity reduced Cx43-mediated gap junction coupling and brain colonization. Database analyses of patient histories revealed increased expression of Cx26 and Cx43 in primary melanoma and breast cancer tumors, respectively, which correlated with increased cancer recurrence and metastasis. Together, our data indicate that Cx43 and Cx26 mediate cancer cell metastasis to the brain and suggest that connexins might be exploited therapeutically to benefit cancer patients with metastatic disease.

  7. Asbestos, cement, and cancer in the right part of the colon.

    PubMed Central

    Jakobsson, K; Albin, M; Hagmar, L

    1994-01-01

    OBJECTIVE--The aim was to investigate associations between exposure to mineral fibres and dust, and cancer in subsites within the large bowel. DESIGN--Pooled retrospective cohort studies. SUBJECTS AND SETTINGS--Blue collar workers, employed for at least one year in different trades; asbestos cement or cement workers (n = 2507), other industrial workers (n = 3965), and fishermen (n = 8092). MAIN OUTCOME MEASURES--Standardised incidence ratios (SIRs, national reference rates) were calculated for cause specific cancer morbidity between 1958 and 1989. The observation period began 15 years after first employment. RESULTS--The asbestos cement and cement workers had a slightly increased risk of colorectal cancer (SIR 1.5; 95% confidence interval (95% CI) 1.1-2.0). This was due to an increase only in the right part of the colon (SIR 2.5; 95% CI 1.6-3.8). The ratio of right (7th revision of the International Classification of Diseases ICD-7) 1530-1531)/left (ICD-7 1532-1533) colon cancer among the asbestos cement and cement workers of 4.8 differed significantly from the ratio both among the other blue collar workers (0.4) and among the fishermen (1.5). As the sensitivity and accuracy was insufficient, mortality data did not show the excess of cancers in the right part of the colon. CONCLUSIONS--An increased incidence of cancer in the right part of the colon was evident in the asbestos cement and cement workers. The distribution of cancers within the colon was noticeably different from that in other blue collar workers, indicating that our findings cannot be explained by socioeconomic confounding factors. A detailed and appropriate disease classification, based on incidence data, is necessary in order not to obscure or underestimate effects of exposure in epidemiological studies on colorectal cancer. PMID:8111470

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

    PubMed

    Rogers, Ailín C; Hanly, Ann M; Collins, Danielle; Baird, Alan W; Winter, Desmond 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.

  9. Metastasis of sigmoid colon cancer in cryptorchid testis: report of a case.

    PubMed

    Rampa, Mario; Battaglia, Luigi; Caprotti, Andrea; Gazzano, Giacomo; Prestianni, Pierpaolo; Muscarà, Cecilia; Vannelli, Alberto

    2012-01-01

    Isolated testicular metastasis from colorectal cancer is considered an unusual event. In this case report we describe for the first time a metastasis from an adenocarcinoma of the sigmoid colon to a cryptorchid testis. The patient developed a painless testicular nodule three years after the diagnosis of primary sigmoid colon cancer. Recent reports have suggested that the incidence of genitourinary abnormalities in human males has increased over the past 50 years; in particular, cryptorchid testes increase the clinical risk factors for primary or metastatic testicular cancer. In conclusion, there should be awareness of the risk of metastasis of colorectal cancer to the testis in the workup of patients with testicular symptoms. Furthermore, patients with colorectal cancer and cryptorchidism should be managed with a single surgical intervention: when the primary colorectal tumor is removed, the cryptorchid testicle should also be removed to reduce the risk of late metastases.

  10. Ectopic expression of the chemokine CXCL17 in colon cancer cells

    PubMed Central

    Ohlsson, Lina; Hammarström, Marie-Louise; Lindmark, Gudrun; Hammarström, Sten; Sitohy, Basel

    2016-01-01

    Background: The novel chemokine CXCL17 acts as chemoattractant for monocytes, macrophages and dendritic cells. CXCL17 also has a role in angiogenesis of importance for tumour development. Methods: Expression of CXCL17, CXCL10, CXCL9 and CCL2 was assessed in primary colon cancer tumours, colon carcinoma cell lines and normal colon tissue at mRNA and protein levels by real-time qRT–PCR, immunohistochemistry, two-colour immunofluorescence and immunomorphometry. Results: CXCL17 mRNA was expressed at 8000 times higher levels in primary tumours than in normal colon (P<0.0001). CXCL17 protein was seen in 17.2% of cells in tumours as compared with 0.07% in normal colon (P=0.0002). CXCL10, CXCL9 and CCL2 mRNAs were elevated in tumours but did not reach the levels of CXCL17. CXCL17 and CCL2 mRNA levels were significantly correlated in tumours. Concordant with the mRNA results, CXCL10- and CXCL9-positive cells were detected in tumour tissue, but at significantly lower numbers than CXCL17. Two-colour immunofluorescence and single-colour staining of consecutive sections for CXCL17 and the epithelial cell markers carcinoembryonic antigen and BerEP4 demonstrated that colon carcinoma tumour cells indeed expressed CXCL17. Conclusions: CXCL17 is ectopically expressed in primary colon cancer tumours. As CXCL17 enhances angiogenesis and attracts immune cells, its expression could be informative for prognosis in colon cancer patients. PMID:26889977

  11. Mechanisms involved in biological behavior changes associated with Angptl4 expression in colon cancer cell lines.

    PubMed

    Huang, Xue-Feng; Han, Jie; Hu, Xiao-Tong; He, Chao

    2012-05-01

    Colorectal cancer (CRC) is one of the most common causes of cancer-related deaths throughout the world. Angiopoietin-like-4 (Angptl4), a member of the angiopoietin family of secreted proteins, is frequently expressed in the perinecrotic areas of different human tumors, yet its role is still unclear in colorectal cancer. Angptl4 mRNA expression in primary colorectal cancer tissue and seven colon cancer cell lines was measured by semi-quantitative RT-PCR; the influence of Angptl4 expression on the colon cancer cell lines was investigated by either overexpression or knockdown of Angptl4 in colon cancer cell lines HCT116 and HT29, respectively. The results showed that Angptl4 mRNA is frequently expressed in human colorectal cancer tissues and cell lines. Overexpression of Angptl4 promoted cell migration, F-actin reorganization and formation of pseudopodia. Further investigation showed that high Angptl4 expression was associated with an increase in ezrin/radixin/moesin and vasodilator-stimulated phosphoprotein expression and a decrease in E-cadherin expression. These results indicate that overexpression of Angptl4 may promote invasion and metastasis in CRC.

  12. A case-control study of toenail selenium and cancer of the breast, colon, and prostate.

    PubMed

    Ghadirian, P; Maisonneuve, P; Perret, C; Kennedy, G; Boyle, P; Krewski, D; Lacroix, A

    2000-01-01

    To study the possible role of dietary and supplementary selenium intake in the etiology of cancer, we carried out a case-control study of breast, colon, and prostate cancer in Montreal between 1989 and 1993. In this study, we were able to interview a total of 1,048 incidence cases of colon (402), breast (414) and prostate (232) cancer subjects and 688 population-based controls matched for age and gender. Of these, a total of 501 cancer cases and 202 controls produced toenail samples for their selenium concentrations, which were determined by neutron activation analysis. We found no association between toenail selenium and breast cancer (odds ratio [OR], 0.72; 95% confidence interval [CI], 0.4-1.31) or prostate cancer (OR, 1.14; 95% CI, 0.46-2.83), though we did observe a statistically significant inverse association between toenail selenium level and the risk of colon cancer for both genders combined (OR, 0.42; 95% CI, 0.19-0.93; P = .009) and for female subjects (P = .050). We also found that nonsmoker case and control subjects had higher selenium in their toenail samples. This could be due either to the nature of tobacco, which reduces selenium absorption, or to smokers' consumption of certain foods containing less selenium. Further epidemiologic studies are required to clarify the role of selenium in the etiology of certain cancers.

  13. Mechanisms of drug resistance in colon cancer and its therapeutic strategies

    PubMed Central

    Hu, Tao; Li, Zhen; Gao, Chun-Ying; Cho, Chi Hin

    2016-01-01

    Drug resistance develops in nearly all patients with colon cancer, leading to a decrease in the therapeutic efficacies of anticancer agents. This review provides an up-to-date summary on over-expression of ATP-binding cassette (ABC) transporters and evasion of apoptosis, two representatives of transport-based and non-transport-based mechanisms of drug resistance, as well as their therapeutic strategies. Different ABC transporters were found to be up-regulated in colon cancer, which can facilitate the efflux of anticancer drugs out of cancer cells and decrease their therapeutic effects. Inhibition of ABC transporters by suppressing their protein expressions or co-administration of modulators has been proven as an effective approach to sensitize drug-resistant cancer cells to anticancer drugs in vitro. On the other hand, evasion of apoptosis observed in drug-resistant cancers also results in drug resistance to anticancer agents, especially to apoptosis inducers. Restoration of apoptotic signals by BH3 mimetics or epidermal growth factor receptor inhibitors and inhibition of cancer cell growth by alternative cell death pathways, such as autophagy, are effective means to treat such resistant cancer types. Given that the drug resistance mechanisms are different among colon cancer patients and may change even in a single patient at different stages, personalized and specific combination therapy is proposed to be more effective and safer for the reversal of drug resistance in clinics. PMID:27570424

  14. Breast cancer: issues in risk reduction, screening and surveillance, early identification and therapy planning.

    PubMed

    Levin, Mark

    2003-01-01

    From May 29 to June 5, 2003, the American Society of Clinical Oncology held its 39th Annual Meeting in Chicago, Illinois, U.S.A. The meeting was devoted to the presentation of advances in clinical sciences, diagnosis, prevention and management of malignant disorders, and brings together investigators, clinicians, policy makers and other professionals interested in the science and impact of cancer worldwide. As a continuation of the report focusing on colon cancer in the last issue of Drug News & Perspectives, this report will focus on breast cancer. .

  15. Performance Analysis of Network Model to Identify Healthy and Cancerous Colon Genes.

    PubMed

    Roy, Tanusree; Barman, Soma

    2016-03-01

    Modeling of cancerous and healthy Homo Sapiens colon gene using electrical network is proposed to study their behavior. In this paper, the individual amino acid models are designed using hydropathy index of amino acid side chain. The phase and magnitude responses of genes are examined to screen out cancer from healthy genes. The performance of proposed modeling technique is judged using various performance measurement metrics such as accuracy, sensitivity, specificity, etc. The network model performance is increased with frequency, which is analyzed using the receiver operating characteristic curve. The accuracy of the model is tested on colon genes and achieved maximum 97% at 10-MHz frequency.

  16. Evaluation of Anti Cancer Effects of DPP-4 Inhibitors in Colon Cancer- An Invitro Study

    PubMed Central

    Kumaravelu, Punnagai; Chellathai, D. Darling

    2015-01-01

    Introduction Among the oral anti-diabetic drugs, Dipeptidyl peptidase - 4(DPP-4) inhibitor is an emerging class of drugs. Inhibitors of DPP-4 enzyme like Sitagliptin and Vildagliptin have shown Anti-oxidant properties in many studies, both invivo and invitro. It has also been characterized as an apoptotic agent on pancreatic cancer cells. In the following study, Anticancer effect of DPP 4 inhibitors on colon cell lines (HT-29) using MTT assay— {3 -4, 5-dimethyl (thiazol – 2 -yl) -3, 5- dimethyl tetrazolium bromide} assay was elucidated. Aim To elucidate and compare the anticancer potential of two DPP 4 inhibitors using in-vitro MTT assay on colorectal cell lines (HT-29). Materials and Methods We treated HT-29 cell lines with two DPP 4 inhibitors. HT-29 cells were incubated at 370C and drug samples were added in various concentrations and incubated for 24 hours. MTT dye was added to the sample and it was incubated for 4 hours. One ml of DMSO was added Using an Ultraviolet-Spectrophotometer, measurement of absorbance was done at 570nm following which the half maximal inhibitory concentration was graphically estimated in relation to the percentage of viability of the cell and the sample concentration. Results We found that both the drugs have shown anticancer activity starting from low to high concentrations when compared with the control using MTT assay. The IC 50 value of Sitagliptin is 31.2 mcg/ml and Vildagliptin is 125 mcg/ml. Conclusion: From this study, we found that the drugs have significant Anti-Cancer property, which would probably play a role as cytotoxic agent in tumour cells. Sitagliptin was found to be more potent than Vildagliptin in colon cancer cell lines. PMID:26816911

  17. The novel HDAC inhibitor AR-42-induced anti-colon cancer cell activity is associated with ceramide production

    SciTech Connect

    Xu, Weihong; Xu, Bin; Yao, Yiting; Yu, Xiaoling; Shen, Jie

    2015-08-07

    In the current study, we investigated the potential activity of AR-42, a novel histone deacetylase (HDAC) inhibitor, against colon cancer cells. Our in vitro results showed that AR-42 induced ceramide production, exerted potent anti-proliferative and pro-apoptotic activities in established (SW-620 and HCT-116 lines) and primary human colon cancer cells. Exogenously-added sphingosine 1-phosphate (S1P) suppressed AR-42-induced activity, yet a cell-permeable ceramide (C4) facilitated AR-42-induced cytotoxicity against colon cancer cells. In addition, AR-42-induced ceramide production and anti-colon cancer cell activity were inhibited by the ceramide synthase inhibitor fumonisin B1, but were exacerbated by PDMP, which is a ceramide glucosylation inhibitor. In vivo, oral administration of a single dose of AR-42 dramatically inhibited SW-620 xenograft growth in severe combined immunodeficient (SCID) mice, without inducing overt toxicities. Together, these results show that AR-42 dramatically inhibits colon cancer cell proliferation in vitro and in vivo, and ceramide production might be the key mechanism responsible for its actions. - Highlights: • AR-42 is anti-proliferative against primary/established colon cancer cells. • AR-42 induces significant apoptotic death in primary/established colon cancer cells. • Ceramide production mediates AR-42-induced cytotoxicity in colon cancer cells. • AR-42 oral administration potently inhibits SW-620 xenograft growth in SCID mice.

  18. Inhibition of SW620 human colon cancer cells by upregulating miRNA-145

    PubMed Central

    Li, Chen; Xu, Na; Li, Yu-Qiang; Wang, Yu; Zhu, Zhi-Tu

    2016-01-01

    AIM: To investigate the targeted inhibition of proliferation and migration of SW620 human colon cancer cells by upregulating miRNA-145 (miR-145). METHODS: Forty-five samples of colon cancer tissues and 45 normal control samples were obtained from the biological database of the First Affiliated Hospital of Liaoning Medical University. We performed quantitative analysis of miR-145 and N-ras expression in tissues; reverse transcriptase polymerase chain reaction analysis of miR-145 expression in SW620 colon cancer cells and normal colonic epithelial cells; construction of miR-145 lentiviral vector and determination of miR-145 expression in SW620 cells transduced with miR-145 vector; analysis of the effect of miR-145 overexpression on SW620 cell proliferation; analysis of the effect of miR-145 overexpression on SW620 cell migration using a wound healing assay; and analysis of the effect of miR-145 on N-ras expression using Western blotting. RESULTS: miR-145 expression was significantly downregulated in colon cancer tissues, with its expression in normal colonic tissues being 4-5-fold higher (two sample t test, P < 0.05), whereas N-ras expression showed the opposite trend. miR-145 expression in SW620 cells was downregulated, which was significantly lower compared to that in colonic epithelial cells (two sample t test, P < 0.05). miR-145 vector and control were successfully packaged; expression of miR-145 in SW620 cells transduced with miR-145 was 8.2-fold of that in control cells (two sample t test, P < 0.05). The proliferation of miR-145-transduced SW620 cells was significantly decreased compared to control cells (two sample t test, P < 0.05). At 48 h in the wound healing experiment, the migration indexes and controls were (97.27% ± 9.25%) and (70.22% ± 6.53%), respectively (two sample t test, P < 0.05). N-ras expression in miR-145-tranduced SW620 cells was significantly lower than others (one-way analysis of variance, P < 0.05). CONCLUSION: miR-145 is important in

  19. Cocoplum (Chrysobalanus icaco L.) anthocyanins exert anti-inflammatory activity in human colon cancer and non-malignant colon cells.

    PubMed

    Venancio, Vinicius P; Cipriano, Paula A; Kim, Hyemee; Antunes, Lusânia M G; Talcott, Stephen T; Mertens-Talcott, Susanne U

    2017-01-25

    Cocoplum (Chrysobalanus icaco L.) (CP) is an anthocyanin-rich fruit found in tropical areas around the globe. CP polyphenols are associated with beneficial effects on health, including reduction of inflammation and oxidative stress. Due to its functional properties, the consumption of this fruit may be beneficial in the promotion of human health and reduce the risk for chronic diseases. The objective of this study was to assess the anti-inflammatory and anti-proliferative activities of anthocyanins extracted from CP (1.0 to 20.0 μg ml(-1) gallic acid equivalents [GAE]) in CCD-18Co non-malignant colonic fibroblasts and HT-29 colorectal adenocarcinoma cells. Tumor necrosis factor alpha (TNF-α, 10 ng mL(-1)) was used to induce inflammation in CCD-18Co cells. CP anthocyanins were identified and quantified using HPLC-ESI-MS(n). The chemical analysis of CP extract identified delphinidin, cyanidin, petunidin and peonidin derivatives as major components. Cell proliferation was suppressed in HT-29 cells at 10.0 and 20.0 μg ml(-1) GAE and this was accompanied by increased intracellular ROS production as well as decreased TNF-α, IL-1β, IL-6, and NF-κB1 expressions at 20.0 μg ml(-1) GAE. Within the same concentration range, there was no cytotoxic effect of CP anthocyanins in CCD-18Co cells and TNF-α-induced intracellular ROS-production was decreased by 17.3%. IL-1β, IL-6 and TNF-α protein expressions were also reduced in TNF-α-treated CCD-18Co cells by CP anthocyanins at 20.0 μg ml(-1) GAE. These results suggest that cocoplum anthocyanins possess cancer-cytotoxic and anti-inflammatory activities in both inflamed colon and colon cancer cells.

  20. Type 2 Diabetes Mellitus Is Associated With Increased Mortality in Chinese Patients Receiving Curative Surgery for Colon Cancer

    PubMed Central

    Chen, Kuo-Hsing; Shao, Yu-Yun; Lin, Zhong-Zhe; Yeh, Yi-Chun; Shau, Wen-Yi; Kuo, Raymond Nienchen; Chen, Ho-Min; Lai, Chiu-Ling; Yeh, Kun-Huei; Cheng, Ann-Lii

    2014-01-01

    Background. We investigated the association between diabetes mellitus (DM) and the prognosis of patients with early colon cancer who had undergone curative surgery. Methods. From three national databases of patients in Taiwan, we selected a cohort of colon cancer patients who had been newly diagnosed with stage I or stage II colon cancer between January 1, 2004 and December 31, 2008 and had undergone curative surgery. We collected information regarding DM (type 2 DM only), the use of antidiabetic medications, other comorbidities, and survival outcomes. The colon cancer-specific survival (CSS) and the overall survival (OS) were compared between patients with and without DM. Results. We selected 6,937 colon cancer patients, among whom 1,371 (19.8%) had DM. The colon cancer patients with DM were older and less likely to receive adjuvant chemotherapy but had a similar tumor stage and grade, compared with colon cancer patients without DM. Compared with colon cancer patients without DM, patients with DM had significantly shorter OS (5-year OS: 71.0% vs. 81.7%) and CSS (5-year CSS: 86.7% vs. 89.2%). After adjusting for age, sex, stage, adjuvant chemotherapy, and comorbidities in our multivariate analysis, DM remained an independent prognostic factor for overall mortality (adjusted hazards ratio: 1.32, 95% confidence interval: 1.18–1.49), but not for cancer-specific mortality. Among the colon cancer patients who had received antidiabetic drug therapy, patients who had used insulin had significantly shorter CSS and OS than patients who had not. Conclusion. Among patients who receive curative surgery for early colon cancer, DM is a predictor of increased overall mortality. PMID:25061090

  1. Gigapixel photography for skin cancer surveillance: a novel alternative to total-body photography.

    PubMed

    Mikailov, Anar; Blechman, Adam

    2013-11-01

    There is substantial evidence supporting the use of cutaneous imaging in combination with standard total-body skin examinations for early detection and treatment of melanoma. In the last 2 decades, total-body photography (TBP) has been widely used in combination with standard total-body skin examinations for active skin cancer surveillance with proven clinical utility; however, the groundbreaking image detail provided by gigapixel photography (GP) could improve dermatologists' ability to monitor suspicious lesions and therefore could serve a critical role in supplementing traditional total-body skin examinations for skin cancer surveillance. Although it has been successfully implemented in other fields, future studies are required to determine the effectiveness of GP in dermatology.

  2. Earlier detection of breast cancer by surveillance of women at familial risk.

    PubMed

    Tilanus-Linthorst, M M; Bartels, C C; Obdeijn, A I; Oudkerk, M

    2000-03-01

    A positive family history increases the risk for breast cancer which oft en occurs at a much younger age than in the general population. We stud ied whether surveillance of these women resulted in the detection of bre ast cancer in an earlier stage than in symptomatic patients with a famil y history. Between January 1994 and April 1998, 294 women with 15-25% r isk (moderate), mean age:43.3 (22-75) years, were screened with a yearly physical examination and mammography from 5 years before the youngest ag e of onset in the family and 384 women with >25% risk (high) for breast cancer, mean age: 42.9 (20-74) years were screened with a physical examination every 6 months and yearly mammography. From September 1995 breast magnetic resonance imaging (MRI) was also carried out for 109 high risk women where mammography showed over 50% density. 26 breast cancers detected under surveillance were significantly more often found in an early T1N0 stage than the 24 breast cancers in patients with a family history referred in that period because of symptoms: 81 versus 46% (P=0.018). Patients under surveillance were also less frequently node-positive than the symptomatic group: 19 versus 42% (P=0.12). 20 patients with a family history referred by our national screening programme in that period had 21 breast cancers detected, 81% in stage T1N0 and 5% node-positive, which was comparable to the results in our national screening programme T1N0 66%, N+ 24% resulting in a 30% reduction in mortality. The incidence in women under surveillance was 10.1 per 1000 in the 'high' risk group and 13.3 per 1000 in the 'moderate' risk group. Expected incidence in an average risk population aged 40-50 years is 1.5, expected if the group consisted of only gene carriers 15 per 1000. 23% of the breast cancers in the surveillance group were detected at physical examination, but occult at mammography. 38% were detected at mammography and clinically occult. Breast MRI (in the subgroup) detected 3 occult

  3. HMG-CoA reductase regulates CCL17-induced colon cancer cell migration via geranylgeranylation and RhoA activation

    SciTech Connect

    Al-Haidari, Amr A.; Syk, Ingvar; Thorlacius, Henrik

    2014-03-28

    Highlights: • Simvastatin blocked CCL17-induced and CCR4-dependent RhoA activation in HT29 cells. • CCL17/CCR4-mediated migration of colon cancer cells was antagonised by simvastatin. • Cell migration recovered by adding Mevalonate and geranylgeranyl pyrophosphate. • Targeting HMG-CoA reductase might be useful to inhibit colon cancer metastasis. - Abstract: Background: Simvastatin is widely used to lower cholesterol levels in patients with cardiovascular diseases, although accumulating evidence suggests that statins, such as simvastatin, also exert numerous anti-tumoral effects. Aim: The aim of this study was to examine the effect of simvastatin on colon cancer cell migration. Methods: Migration assays were performed to evaluate CCL17-induced colon cancer cell (HT-29) chemotaxis. In vitro tumor growth and apoptosis were assessed using a proliferation assay and annexin V assay, respectively. Active RhoA protein levels in CCL17-stimulated colon cancer cells were quantified using a G-LISA assay. Results: We found that simvastatin dose-dependently decreased CCL17-induced colon cancer cell migration. Simvastatin had no effect on colon cancer cell proliferation or apoptosis. Inhibition of beta chemokine receptor 4, CCR4, reduced CCL17-evoked activation of RhoA in colon cancer cells. Moreover, administration of mevalonate reversed the inhibitory effect of simvastatin on CCL17-induced colon cancer cell migration. Interestingly, co-incubation with geranylgeranyl pyrophosphate (GGPP) antagonized the inhibitory impact of simvastatin on colon cancer cell migration triggered by CCL17. Moreover, we observed that simvastatin decreased CCL17-induced activation of RhoA in colon cancer cells. Administration of mevalonate and GGPP reversed the inhibitory effect of simvastatin on CCL17-provoked RhoA activation in colon cancer cells. Conclusions: Taken together, our findings show for the first time that HMG-CoA reductase regulates CCL17-induced colon cancer cell migration via

  4. Effects of silk sericin on the proliferation and apoptosis of colon cancer cells.

    PubMed

    Kaewkorn, Waraporn; Limpeanchob, Nanteetip; Tiyaboonchai, Waree; Pongcharoen, Sutatip; Sutheerawattananonda, Manote

    2012-01-01

    Sericin is a silk protein woven from silkworm cocoons (Bombyx mori). In animal model, sericin has been reported to have anti-tumoral action against colon cancer. The mechanisms underlying the activity of sericin against cancer cells are not fully understood. The present study investigated the effects of sericin on human colorectal cancer SW480 cells compared to normal colonic mucosal FHC cells. Since the size of the sericin protein may be important for its activity, two ranges of molecular weight were tested. Sericin was found to decrease SW480 and FHC cell viability. The small sericin had higher anti-proliferative effects than that of the large sericin in both cell types. Increased apoptosis of SW480 cells is associated with increased caspase-3 activity and decreased Bcl-2 expression. The anti-proliferative effect of sericin was accompanied by cell cycle arrest at the S phase. Thus, sericin reduced SW480 cell viability by inducing cell apoptosis via caspase-3 activation and down-regulation of Bcl-2 expression. The present study provides scientific data that support the protective effect of silk sericin against cancer cells of the colon and suggests that this protein may have significant health benefits and could potentially be developed as a dietary supplement for colon cancer prevention.

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

    PubMed Central

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

    2016-01-01

    Background 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. Results 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. Materials and Methods 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. Conclusions 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. PMID:27418137

  6. Adenosine induces apoptosis through TNFR1/RIPK1/P38 axis in colon cancer cells.

    PubMed

    Yu, Shunji; Hou, Daisen; Chen, Ping; Zhang, Qi; Lv, Bin; Ma, Yunfang; Liu, Fuchen; Liu, Hui; Song, Evelyn J; Yang, Dongqin; Liu, Jie

    2015-05-08

    Adenosine, a metabolite of ATP, ubiquitously exists in a wide range of organs and tissues. We previously reported that adenosine was implicated in apoptosis in many cancer cells by extrinsic and/or intrinsic pathways. Here, we found that adenosine suppresses the cell growth by induction of apoptosis of human colonic cancer cells through a novel mechanism. Adenosine suppresses the cell growth of human SW620 and SW480 colon cells in an adenosine transporter and adenosine kinase dependent manner. Moreover, the cell growth suppression is induced by apoptosis through activation of caspase-3 and PARP, and accumulation of ROS in cells. Importantly, we found that adenosine increases the expression of TNFR1 and RIPK1 and the phosphorylation of p38. Knockdown of TNFR1 or RIPK1 impairs the activation of p38, blocks the cleavage of PARP, and provides partially, yet significantly protection from cell death, including reducing the ROS generation in the colon cancer cells. These results indicate that a TNFR1/RIPK1/P38 axis is present in adenosine-induced apoptosis of colonic cancer cells. This axis triggers apoptosis and plays crucial roles in relay of the death signaling. Our study also provides additional experimental evidence for adenosine as a potent therapeutic drug in cancer therapy.

  7. Prognostic and predictive significance of MSI in stages II/III colon cancer.

    PubMed

    Saridaki, Zacharenia; Souglakos, John; Georgoulias, Vassilis

    2014-06-14

    In colon cancer, classic disease staging remains the key prognosis and treatment determinant. Although adjuvant chemotherapy has an established role in stage III colon cancer patients, in stage II it is still a subject of controversy due to its restriction to a small subgroup of patients with high-risk histopathologic features. Patients with stage II tumors form a highly heterogeneous group, with five-year relative overall survival rates ranging from 87.5% (IIA) to 58.4% (IIC). Identifying those for whom adjuvant chemotherapy would be appropriate and necessary has been challenging, and prognostic markers which could serve in the selection of patients more likely to recur or benefit from adjuvant chemotherapy are eagerly needed. The stronger candidate in this category seems to be microsatellite instability (MSI). The recently reported European Society for Medical Oncology guidelines suggest that MSI should be evaluated in stage II colorectal cancer patients in order to contribute in treatment decision-making regarding chemotherapy administration. The hypothetical predictive role of MSI regarding its response to 5-fluorouracil-based adjuvant chemotherapy has proven a much more difficult issue to address. Almost every possible relation between MSI and chemotherapy outcome has been described in the adjuvant colon cancer setting in the international literature, and the matter is far from being settled. In this current report we critically evaluate the prognostic and predictive impact of MSI status in patients with stage II and stage III colon cancer patients.

  8. Pathological implications of Cx43 down-regulation in human colon cancer.

    PubMed

    Ismail, Rehana; Rashid, Rabiya; Andrabi, Khurshid; Parray, Fazl Q; Besina, Syed; Shah, Mohd Amin; Ul Hussain, Mahboob

    2014-01-01

    Connexin 43 is an important gap junction protein in vertebrates and is known for its tumor suppressive properties. Cx43 is abundantly expressed in the human intestinal epithelial cells and muscularis mucosae. To explore the role of Cx43 in the genesis of human colon cancer, we performed the expression analysis of Cx43 in 80 cases of histopathologically confirmed and clinically diagnosed human colon cancer samples and adjacent control tissue and assessed correlations with clinicopathological variables. Western blotting using anti-Cx43 antibody indicated that the expression of Cx43 was significantly down regulated (75%) in the cancer samples as compared to the adjacent control samples. Moreover, immunohistochemical analysis of the tissue samples confirmed the down regulation of the Cx43 in the intestinal epithelial cells. Cx43 down regulation showed significant association (p<0.05) with the histological type and tumor invasion properties of the cancer. Our data demonstrated that loss of Cx43 may be an important event in colon carcinogenesis and tumor progression, providing significant insights about the tumor suppressive properties of the Cx43 and its potential as a diagnostic marker for colon cancer.

  9. Antiproliferative activity of tea catechins associated with casein micelles, using HT29 colon cancer cells.

    PubMed

    Haratifar, S; Meckling, K A; Corredig, M

    2014-02-01

    Numerous studies have shown that green tea polyphenols display anticancer activities in many organ sites by using different experimental models in rodents and in cultured cell lines in vitro. The present study tested the ability of casein micelles to deliver biologically active concentrations of polyphenols to HT-29 colon cancer cells. Epigallocatechin gallate (EGCG), the major catechin found in green tea, was used as the model molecule, as it has been shown to have antiproliferative activity on colon cancer cells. In the present work, we hypothesized that due to the binding of caseins with EGCG, casein micelles may be an ideal platform for the delivery of this bioactive molecule and that the binding would not affect the bioaccessibility of EGCG. The cytotoxicity and proliferation behavior of HT-29 colon cancer cells when exposed to free EGCG was compared with that of nanoencapsulated EGCG in casein micelles of skim milk. Epigallocatechin gallate-casein complexes were able to decrease the proliferation of HT-29 cancer cells, demonstrating that bioavailability may not be reduced by the nanoencapsulation. As casein micelles may act as protective carriers for EGCG in foods, it was concluded that nanoencapsulation of tea catechins in casein micelles may not diminish their antiproliferative activity on colon cancer cells compared with free tea catechins.

  10. Coffee phenolic phytochemicals suppress colon cancer metastasis by targeting MEK and TOPK.

    PubMed

    Kang, Nam Joo; Lee, Ki Won; Kim, Bo Hyun; Bode, Ann M; Lee, Hyo-Jeong; Heo, Yong-Seok; Boardman, Lisa; Limburg, Paul; Lee, Hyong Joo; Dong, Zigang

    2011-06-01

    Epidemiological studies suggest that coffee consumption reduces the risk of cancers, including colon cancer, but the molecular mechanisms and target(s) underlying the chemopreventive effects of coffee and its active ingredient(s) remain unknown. Based on serving size or daily units, coffee contains larger amounts of phenolic phytochemicals than tea or red wine. Coffee or chlorogenic acid inhibited CT-26 colon cancer cell-induced lung metastasis by blocking phosphorylation of ERKs. Coffee or caffeic acid (CaA) strongly suppressed mitogen-activated MEK1 and TOPK activities and bound directly to either MEK1 or TOPK in an ATP-noncompetitive manner. Coffee or CaA, but not caffeine, inhibited ERKs phosphorylation, AP-1 and NF-κB transactivation and subsequently inhibited TPA-, EGF- and H-Ras-induced neoplastic transformation of JB6 P+ cells. Coffee consumption was also associated with a significant attenuation of ERKs phosphorylation in colon cancer patients. These results suggest that coffee and CaA target MEK1 and TOPK to suppress colon cancer metastasis and neoplastic cell transformation.

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

    PubMed

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

    2012-05-11

    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.

  12. MicroRNAs as Regulator of Signaling Networks in Metastatic Colon Cancer

    PubMed Central

    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

  13. Vancomycin-sensitive bacteria trigger development of colitis-associated colon cancer by attracting neutrophils

    PubMed Central

    Tanaka, Yuriko; Ito, Sachiko; Isobe, Ken-ichi

    2016-01-01

    Inflammatory bowel disease confers an increased risk of developing colitis-associated colon cancer (CAC). During the active colitis or developing tumor stage, commensal bacteria show dynamic translocation. However, whether alteration of the bacterial composition in the gut causes CAC is still unclear. To clarify the effect of commensal bacteria on CAC development, we employed an azoxymethane (AOM) and dextran sodium sulfate (DSS)-induced murine CAC model treated with or without antibiotics. In addition, we analyzed the effects of antibiotics on infiltration of myeloid cells, colonic inflammatory responses, and colorectal cancer formation. We found that vancomycin treatment dramatically suppressed tumor development. In addition, AOM/DSS treatment greatly induced the infiltration of Gr-1high/CD11bhigh neutrophils to the colon, which led to the production of tumor necrosis factor α and inducible nitric oxide synthase. Vancomycin treatment suppressed the infiltration of neutrophils induced by AOM/DSS. Moreover, vancomycin treatment greatly reduced the colon injury and DNA damage caused by AOM/DSS-induced NO radicals. Our results indicate that vancomycin-sensitive bacteria induced colon inflammation and DNA damage by attracting neutrophils into damaged colon tissue, thus promoting tumor formation. PMID:27050089

  14. Vancomycin-sensitive bacteria trigger development of colitis-associated colon cancer by attracting neutrophils.