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Sample records for nonmetastatic colon cancer

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

    International Nuclear Information System (INIS)

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

    2010-01-01

    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.

  2. The Early Prostate Cancer program: bicalutamide in nonmetastatic prostate cancer

    DEFF Research Database (Denmark)

    Iversen, Peter; Roder, Martin Andreas; Røder, Martin Andreas

    2008-01-01

    The Early Prostate Cancer program is investigating the addition of bicalutamide 150 mg to standard care for localized or locally advanced, nonmetastatic prostate cancer. The third program analysis, at 7.4 years' median follow-up, has shown that bicalutamide 150 mg does not benefit patients...

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

    Science.gov (United States)

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

    2012-01-01

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

  4. Prognostic significance of unintentional body weight loss in colon cancer patients.

    Science.gov (United States)

    Kuo, Yi-Hung; Shi, Chung-Sheng; Huang, Cheng Yi; Huang, Yun-Ching; Chin, Chih-Chien

    2018-04-01

    The aim of the present study was to investigate whether unintentional body weight loss (BWL) provides additional clinical information in terms of tumor progression and prognosis in non-metastatic colon cancer. In the present study, a total of 2,406 consecutive colon cancer patients without metastasis were retrospectively enrolled. Unintentional BWL was defined as loss of >5% of body weight within the last 6-12 months, or defined subjectively upon fulfillment of at least two of the following: Evidence of change in clothing size and corroboration of the reported weight loss by family or friend. This category was recorded as present ('with') or absent ('without'). Logistic regression analysis was performed to determine the correlation between BWL and the tumor characteristics and post-operative outcomes of patients with colon cancer. The Cox regression model was used to determine the association of BWL with long-term survival of colon cancer patients. A significant association between BWL and tumor location [right vs. left: Odds ratio (OR)=1.62; Pcolon cancer is not just a symptom, but it is also correlated with tumor location, size and depth, and is a prognostic factor for poor outcomes including overall survival and tumor relapse.

  5. Importance of Metastatic Lymph Node Ratio in Non-Metastatic, Lymph Node-Invaded Colon Cancer: A Clinical Trial

    Science.gov (United States)

    Isik, Arda; Peker, Kemal; Firat, Deniz; Yilmaz, Bahri; Sayar, Ilyas; Idiz, Oguz; Cakir, Coskun; Demiryilmaz, Ismail; Yilmaz, Ismayil

    2014-01-01

    Background The aim of this study was to evaluate the prognostic importance of the metastatic lymph node ratio for stage III colon cancer patients and to find a cut-off value at which the overall survival and disease-free survival change. Material/Methods Patients with pathological stage III colon cancer were retrospectively evaluated for: age; preoperative values of Crp, Cea, Ca 19-9, and Afp; pathologic situation of vascular, perineural, lymphatic, and serosal involvement; and metastatic lymph node ratio values were calculated. Results The study included 58 stage III colon cancer patients: 20 (34.5%) females and 38 (65.5%) males were involved in the study. Multivariate analysis was applied to the following variables to evaluate significance for overall survival and disease-free survival: age, Crp, Cea, perineural invasion, and metastatic lymph node ratio. The metastatic lymph node ratio (<0.25 or ≥0.25) is the only independent variable significant for overall and disease-free survival. Conclusions Metastatic lymph node ratio is an ideal prognostic marker for stage III colon cancer patients, and 0.25 is the cut-off value for prognosis. PMID:25087904

  6. External validation of models predicting the individual risk of metachronous peritoneal carcinomatosis from colon and rectal cancer.

    Science.gov (United States)

    Segelman, J; Akre, O; Gustafsson, U O; Bottai, M; Martling, A

    2016-04-01

    To externally validate previously published predictive models of the risk of developing metachronous peritoneal carcinomatosis (PC) after resection of nonmetastatic colon or rectal cancer and to update the predictive model for colon cancer by adding new prognostic predictors. Data from all patients with Stage I-III colorectal cancer identified from a population-based database in Stockholm between 2008 and 2010 were used. We assessed the concordance between the predicted and observed probabilities of PC and utilized proportional-hazard regression to update the predictive model for colon cancer. When applied to the new validation dataset (n = 2011), the colon and rectal cancer risk-score models predicted metachronous PC with a concordance index of 79% and 67%, respectively. After adding the subclasses of pT3 and pT4 stage and mucinous tumour to the colon cancer model, the concordance index increased to 82%. In validation of external and recent cohorts, the predictive accuracy was strong in colon cancer and moderate in rectal cancer patients. The model can be used to identify high-risk patients for planned second-look laparoscopy/laparotomy for possible subsequent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Colorectal Disease © 2015 The Association of Coloproctology of Great Britain and Ireland.

  7. Evaluation of dual energy spectral CT in differentiating metastatic from non-metastatic lymph nodes in rectal cancer: Initial experience

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Huanhuan [Department of Radiology, Ruijin Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai 200025 (China); Department of Radiology, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine (China); Yan, Fuhua; Pan, Zilai; Lin, Xiaozhu; Luo, Xianfu; Shi, Cen [Department of Radiology, Ruijin Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai 200025 (China); Chen, Xiaoyan [Department of Pathology, Ruijin Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai 200025 (China); Wang, Baisong [Department of Biomedical Statistics, Shanghai Jiaotong University, School of Medicine, Shanghai 200025 (China); Zhang, Huan, E-mail: huanzhangy@126.com [Department of Radiology, Ruijin Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai 200025 (China)

    2015-02-15

    Highlights: • Colorectal cancer is the third most prevalent cancer and the status of the regional lymph nodes in rectal cancer is considered to be one of the most powerful prognostic factor in the absence of distant metastatic disease. Detecting LNs metastasis is still a challenging problem due to the presence of microscopic metastasis or inflammatory swelling of LNs. • We investigated the value of dual energy spectral CT in differentiating metastatic from non-metastatic lymph nodes in rectal cancer. Our study demonstrated that the quantitative normalized iodine concentration (nIC) could be useful for differentiating metastatic and non-metastatic lymph nodes. The combination of nIC in portal venous phase and conventional size criterion could improve the diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive value of rectal cancer. - Abstract: Objectives: To investigate the value of dual energy spectral CT (DEsCT) imaging in differentiating metastatic from non-metastatic lymph nodes in rectal cancer. Methods: Fifty-five patients with rectal cancer underwent the arterial phase (AP) and portal venous phase (PP) contrast-enhanced DEsCT imaging. The virtual monochromatic images and iodine-based material decomposition images derived from DEsCT imaging were interpreted for lymph nodes (LNs) measurement. The short axis diameter and the normalized iodine concentration (nIC) of metastatic and non-metastatic LNs were measured. The two-sample t test was used to compare the short axis diameters and nIC values of metastatic and non-metastatic LNs. ROC analysis was performed to assess the diagnostic performance. Results: One hundred and fifty two LNs including 92 non-metastatic LNs and 60 metastatic LNs were matched using the radiological-pathological correlation. The mean short axis diameter of metastatic LNs was significantly larger than that of the non-metastatic LNs (7.28 ± 2.28 mm vs. 4.90 ± 1.64 mm, P < 0.001). The mean n

  8. Colon cancer

    Science.gov (United States)

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

  9. Evidence for the prevention of bone loss in elderly and old early non-metastatic breast cancer patients treated with aromatase inhibitors

    DEFF Research Database (Denmark)

    Gunmalm, V.; Jørgensen, N. R.; Abrahamsen, B.

    2017-01-01

    Breast cancer (BC) is the most common cancer amongst women worldwide. Bone health is emerging as an important issue for BC survivors. In this literature study, we focus on agents for preventing bone loss in early non-metastatic estrogen receptor positive BC in treatment with aromatase inhibitors...... (AI) and to assess the evidence for antiresorptive treatment of bone loss in early non-metastatic breast cancer. We included randomized controlled trials (RCT's) comparing: (a) bisphosphonates and control; (b) different bisphosphonates; (c) denosumab and control and (d) bisphosphonates vs. denosumab...... in early non-metastatic BC women in AI treatment. Among antiresorptives, zoledronic acid currently has the highest evidence for prevention of AI associated bone loss in early non-metastatic BC. Data on fracture prevention among all patients, elderly and old is sparse. More randomized controlled studies...

  10. Personality variables as predictors of early non-metastatic colorectal cancer patients' psychological distress and health-related quality of life: a one-year prospective study.

    Science.gov (United States)

    Hyphantis, Thomas; Paika, Vassiliki; Almyroudi, Augoustina; Kampletsas, Eleftherios O; Pavlidis, Nicholas

    2011-05-01

    We aimed to assess the course of early non-metastatic colorectal cancer patients' psychological distress and health-related quality of life (HRQOL) and to identify relevant clinical and psychological predictors during a one-year period. Of the 144 early non-metastatic colorectal cancer patients initially assessed for psychological distress symptoms (SCL-90-R), HRQOL (WHOQOL-BREF), sense of coherence (SOC), defense mechanisms (LSI) and hostility (HDHQ), 84 (58.3%) completed the one-year follow-up. Mean (SD) age was 65.1 (9.8) years and 67.4% were male. Mean (SD) disease duration was 1.7 (2.2) years, with 49.3% being diagnosed within the last six months. In 75.0% the site was at colon and in 25.0% at rectum; 2.1% had stage I, 59.0% stage II and 38.9% stage III disease. Paranoid ideation, psychoticism, interpersonal sensitivity, anxiety and depressive symptoms increased significantly over the one-year period of the study and most of the HRQOL components were significantly decreased over the same period. Men were at greater risk for further developing depressive symptomatology. Low SOC was independent predictor of depression, while hostility independently predicted anxiety, interpersonal sensitivity and psychoticism symptoms. General psychological distress and low SOC were independent predictors of HRQOL, while repression was also an independent predictor of Physical HRQOL. In early non-metastatic colorectal cancer patients, psychological distress symptoms are increased and HRQOL is decreased over one-year period. Symptoms of psychological distress are strong predictors of HRQOL, while personality variables can also predict psychological distress symptoms' increase and HRQOL decrease over time, and this could be relevant to psychological interventions. Copyright © 2010 Elsevier Inc. All rights reserved.

  11. The Use of Re-irradiation in Locally Recurrent, Non-metastatic Rectal Cancer.

    Science.gov (United States)

    Susko, Matthew; Lee, Jason; Salama, Joseph; Thomas, Samantha; Uronis, Hope; Hsu, David; Migaly, John; Willett, Christopher; Czito, Brian; Palta, Manisha

    2016-10-01

    The optimal approach to patients with locally recurrent, non-metastatic rectal cancer is unclear. This study evaluates the outcomes and toxicity associated with pelvic re-irradiation. Patients undergoing re-irradiation for locally recurrent, non-metastatic, rectal cancer between 2000 and 2014 were identified. Acute and late toxicities were assessed using common terminology criteria for adverse events version 4.0. Disease-related endpoints included palliation of local symptoms, surgical outcomes, and local progression-free survival (PFS), distant PFS and overall survival (OS) using the Kaplan-Meier method. Thirty-three patients met the criteria for inclusion in this study. Two (6 %) experienced early grade 3+ toxicity and seven (21 %) experienced late grade 3+ toxicity. Twenty-three patients presented with symptomatic local recurrence and 18 (78 %) reported symptomatic relief. Median local PFS was 8.7 (95 % CI 3.8-15.2) months, with a 2-year rate of 15.7 % (4.1-34.2), and median time to distant progression was 4.4 (2.2-33.3) months, with a 2-year distant PFS rate of 38.9 % (20.1-57.3). Median OS time for patients was 23.1 (11.1-33.0) months. Of the 14 patients who underwent surgery, median survival was 32.3 (13.8-48.0) months compared with 13.3 (2.2-33.0) months in patients not undergoing surgery (p = 0.10). A margin-negative (R0) resection was achieved in 10 (71 %) of the surgeries. Radiation treatment modality (intensity-modulated radiation therapy, three-dimensional conformal radiotherapy, intraoperative radiation therapy) did not influence local or distant PFS or OS. Re-irradiation is a beneficial treatment modality for the management of locally recurrent, non-metastatic rectal cancer. It is associated with symptom improvement, low rates of toxicity, and similar benefits among radiation modalities.

  12. Bicalutamide monotherapy compared with castration in patients with nonmetastatic locally advanced prostate cancer

    DEFF Research Database (Denmark)

    Iversen, P; Tyrrell, C J; Kaisary, A V

    2000-01-01

    Nonsteroidal antiandrogen monotherapy may be a treatment option for some patients with advanced prostate cancer. We report a survival and safety update from an analysis of 2 studies in which patients with nonmetastatic (M0) locally advanced disease were treated with either 150 mg. bicalutamide mo...

  13. Casodex (bicalutamide) 150-mg monotherapy compared with castration in patients with previously untreated nonmetastatic prostate cancer

    DEFF Research Database (Denmark)

    Iversen, P; Tyrrell, C J; Kaisary, A V

    1998-01-01

    To compare the efficacy, tolerability, and quality of life benefits of bicalutamide (Casodex) 150-mg/day monotherapy and castration in previously untreated nonmetastatic (M0) advanced prostate cancer....

  14. Outcomes After Intensity-Modulated Versus Conformal Radiotherapy in Older Men With Nonmetastatic Prostate Cancer

    International Nuclear Information System (INIS)

    Bekelman, Justin E.; Mitra, Nandita; Efstathiou, Jason; Liao Kaijun; Sunderland, Robert; Yeboa, Deborah N.; Armstrong, Katrina

    2011-01-01

    Purpose: There is little evidence comparing complications after intensity-modulated (IMRT) vs. three-dimensional conformal radiotherapy (CRT) for prostate cancer. The study objective was to test the hypothesis that IMRT, compared with CRT, is associated with a reduction in bowel, urinary, and erectile complications in elderly men with nonmetastatic prostate cancer. Methods and Materials: We undertook an observational cohort study using registry and administrative claims data from the SEER-Medicare database. We identified men aged 65 years or older diagnosed with nonmetastatic prostate cancer in the United States between 2002 and 2004 who received IMRT (n = 5,845) or CRT (n = 6,753). The primary outcome was a composite measure of bowel complications. Secondary outcomes were composite measures of urinary and erectile complications. We also examined specific subsets of bowel (proctitis/hemorrhage) and urinary (cystitis/hematuria) events within the composite complication measures. Results: IMRT was associated with reductions in composite bowel complications (24-month cumulative incidence 18.8% vs. 22.5%; hazard ratio [HR] 0.86; 95% confidence interval [CI], 0.79–0.93) and proctitis/hemorrhage (HR 0.78; 95% CI, 0.64–0.95). IMRT was not associated with rates of composite urinary complications (HR 0.93; 95% CI, 0.83–1.04) or cystitis/hematuria (HR 0.94; 95% CI, 0.83–1.07). The incidence of erectile complications involving invasive procedures was low and did not differ significantly between groups, although IMRT was associated with an increase in new diagnoses of impotence (HR 1.27, 95% CI, 1.14–1.42). Conclusion: IMRT is associated with a small reduction in composite bowel complications and proctitis/hemorrhage compared with CRT in elderly men with nonmetastatic prostate cancer.

  15. Concerns about Breast Cancer, Pain, and Fatigue in Non-Metastatic Breast Cancer Patients Undergoing Primary Treatment

    Directory of Open Access Journals (Sweden)

    Chelsea R. Amiel

    2016-08-01

    Full Text Available Women diagnosed with breast cancer often endorse psychosocial concerns prior to treatment, which may influence symptom experiences. Among these, low perceived social support relates to elevated fatigue. Those with low social support perceptions may also experience a greater sense of rejection. We sought to determine if social rejection concerns post-surgery predict fatigue interference 12 months later in women with non-metastatic breast cancer. Depressive symptoms and pain severity after completion of adjuvant therapy (six months post-surgery were examined as potential mediators. Women (N = 240 with non-metastatic breast cancer were recruited 2–10 weeks post-surgery. Multiple regression analyses examined relationships among variables adjusting for relevant covariates. Greater rejection concerns at study entry predicted greater fatigue interference 12 months later (p < 0.01. Pain severity after adjuvant therapy partially mediated the relationship between social rejection concerns and fatigue interference, with significant indirect (β = 0.06, 95% CI (0.009, 0.176 and direct effects (β = 0.18, SE = 0.07, t(146 = 2.78, p < 0.01, 95% CI (0.053, 0.311. Therefore, pain levels post-treatment may affect how concerns of social rejection relate to subsequent fatigue interference. Interventions targeting fears of social rejection and interpersonal skills early in treatment may reduce physical symptom burden during treatment and into survivorship.

  16. Aspirin therapy reduces the ability of platelets to promote colon and pancreatic cancer cell proliferation: Implications for the oncoprotein c-MYC

    Science.gov (United States)

    Sylman, Joanna L.; Ngo, Anh T. P.; Pang, Jiaqing; Sears, Rosalie C.; Williams, Craig D.; McCarty, Owen J. T.

    2017-01-01

    Aspirin, an anti-inflammatory and antithrombotic drug, has become the focus of intense research as a potential anticancer agent owing to its ability to reduce tumor proliferation in vitro and to prevent tumorigenesis in patients. Studies have found an anticancer effect of aspirin when used in low, antiplatelet doses. However, the mechanisms through which low-dose aspirin works are poorly understood. In this study, we aimed to determine the effect of aspirin on the cross talk between platelets and cancer cells. For our study, we used two colon cancer cell lines isolated from the same donor but characterized by different metastatic potential, SW480 (nonmetastatic) and SW620 (metastatic) cancer cells, and a pancreatic cancer cell line, PANC-1 (nonmetastatic). We found that SW480 and PANC-1 cancer cell proliferation was potentiated by human platelets in a manner dependent on the upregulation and activation of the oncoprotein c-MYC. The ability of platelets to upregulate c-MYC and cancer cell proliferation was reversed by an antiplatelet concentration of aspirin. In conclusion, we show for the first time that inhibition of platelets by aspirin can affect their ability to induce cancer cell proliferation through the modulation of the c-MYC oncoprotein. PMID:27903583

  17. CT in colon cancer

    International Nuclear Information System (INIS)

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

    1990-01-01

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

  18. Anxiety and its time courses during radiotherapy for non-metastatic breast cancer: A longitudinal study

    OpenAIRE

    Lewis, Florence; Merckaert, Isabelle; Liénard, Aurore; Libert, Yves; Etienne, Anne-Marie; Reynaert, Christine; Slachmuylder, Jean-Louis; Scalliet, Pierre; Van Houtte, Paul; COUCKE, Philippe; Salamon, Emile; Razavi, Darius

    2014-01-01

    Purpose: To our knowledge, no study has specifically assessed the time course of anxiety during radiotherapy (RT). The objective of this study was to assess anxiety time courses in patients with nonmetastatic breast cancer. Material and methods: This multicenter, descriptive longitudinal study included 213 consecutive patients with breast cancer who completed visual analog scales (VASs) assessing state anxiety before and after the RT simulation and the first and last five RT se...

  19. Study of Endothelin-1 and Vascular Endothelial Growth Factor in Patients with Cancer Colon

    International Nuclear Information System (INIS)

    ABDEL-GAWAD, I.A.; HASSANEIN, H.M.R.; BAHGAT, N.A.; ABDEL SATTAR, M.A.; EL-SISSY, A.H.; ALTAWEEL, M.A.; HELAL, A.M.

    2008-01-01

    Purpose: The levels of endothelin-1 and VEGF were evaluated in the sera of newly diagnosed patients with cancer colon and were compared with the routinely used tumor markers; CEA and CA19.9. Their relations with some prognostic factors of cancer colon were also investigated. Subjects and Methods: The study included 48 patients with cancer colon and 20 apparently healthy volunteers as a control group. Patients were 23 males and 25 females with age range from 18 to 71 years (mean = 47±1.8). Both serum and plasma samples were obtained from patients and controls. Results: Six percent of patients had grade 1 tumors, 77% had grade 2 and 17% had grade 3 disease. As regard to the stage, 52% of patients were stage II, 35.5% were stage III, while 12.5% were stage IV. Liver metastasis was present in 12.5%, while 35% showed lymph node metastasis. The VEGF, endothelin-1, CA 19.9 and CEA were significantly higher in the cancer colon patients than in control groups (p-value <0.001, 0.006, <0.001 and <0.001; respectively). Plasma level of endothelin-1 and serum level of VEGF showed significantly higher levels in advanced stages of the disease (p value <0 .001) and in presence of liver metastasis (p value <0.001 and 0.002 respectively), while VEGF showed significant result when compared with the grade (p value=0.032). In this study, when comparing the levels of plasma endothelin-1 and serum VEGF between the metastatic, non-metastatic liver patients of the cancer colon group and the control group, the comparison was statistically significant for both markers (p<0.001). Endothelin-1 and VEGF showed significant positive correlation (r=0.77 and p-value <0.0001). Serum VEGF and CA 19.9 showed good sensitivities which were not different (97.9% and 87.5%; respectively), while there was no significant difference between VEGF, CA 19.9 and CEA with respect to specificities (100%, 90% and 100% respectively). Conclusion: Both endothelin-1 and VEGF may be used for early detection of liver

  20. CT Findings of Colonic Complications Associated with Colon Cancer

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  1. CT Findings of Colonic Complications Associated with Colon Cancer

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-04-15

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

  2. Imaging tests in staging and surveillance of non-metastatic breast cancer: changes in routine clinical practice and cost implications.

    Science.gov (United States)

    De Placido, S; De Angelis, C; Giuliano, M; Pizzi, C; Ruocco, R; Perrone, V; Bruzzese, D; Tommasielli, G; De Laurentiis, M; Cammarota, S; Arpino, G; Arpino, G

    2017-03-14

    Although guidelines do not recommend computerised tomography (CT), positron emission tomography (PET) or magnetic resonance imaging (MRI) for the staging or follow-up of asymptomatic patients with non-metastatic breast cancer, they are often requested in routine clinical practice. The aim of this study was to determine the staging and follow-up patterns, and relative costs in a large population of breast cancer patients living and treated in a Southern Italian region. We analysed the clinical computerised information recorded by 567 primary-care physicians assisting about 650 000 inhabitants in the Campania region. Patients with non-metastatic breast cancer were identified and divided into calendar years from 2001 to 2010. The number of diagnostic tests prescribed per 100 patients (N/Pts) and the mean cost per patient was determined 3 months before diagnosis and up to 1 year after diagnosis. Costs are expressed in constant 2011 euros. We identified 4680 newly diagnosed cases of asymptomatic non-metastatic breast cancer. N/Pts increased significantly (Ptests'), and costs was unchanged. However, the number of CT, PET scans and MRI ('new tests')prescriptions almost quadrupled and the mean cost per patient related to these procedures significantly increased from [euro ]357 in 2001 to [euro ]830 in 2010 (Ptest prescriptions and relative costs significantly and steadily increased throughout the study period. At present there is no evidence that the delivery of new tests to asymptomatic patients improves breast cancer outcome. Well-designed clinical trials are urgently needed to shed light on the impact of these tests on clinical outcome and overall survival.

  3. Colon cancer associated transcripts in human cancers.

    Science.gov (United States)

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

    2017-10-01

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

  4. Differentiation of Metastatic and Non-Metastatic Mesenteric Lymph Nodes by Strain Elastography in Surgical Specimens

    DEFF Research Database (Denmark)

    Havre, R F; Leh, S M; Gilja, O H

    2016-01-01

    Purpose: To investigate if strain elastography could differentiate between metastatic and non-metastatic mesenteric lymph nodes ex-vivo. Materials and Methods: 90 mesenteric lymph nodes were examined shortly after resection from 25 patients including 17 patients with colorectal cancer and 8...... patients with Crohn's disease. Ultrasound-based strain elastography was performed with a linear probe. Tissue hardness in lymph nodes was assessed using visual scales and measuring the strain ratio. B-mode characteristics were also recorded. Pathological diagnosis with grading of fibrosis served...... non-metastatic nodes, but the difference was not significant (65.5 vs. 55.0, p = 0.055). There was no difference between lymph nodes in Crohn's and non-metastatic cancer specimens. The metastatic lymph nodes were significantly more fibrotic than the non-metastatic lymph nodes by the ordinal fibrosis...

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

    Science.gov (United States)

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

    2013-08-01

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

  6. Differentiating metastatic from nonmetastatic lymph nodes in cervical cancer patients using monoexponential, biexponential, and stretched exponential diffusion-weighted MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Qingxia; Wang, Meiyun; Shi, Dapeng [Radiological Department of Henan Provincial People' s Hospital, Zhengzhou, Henan (China); Zheng, Dandan [GE Healthcare, MR Research China, Beijing (China); Shi, Ligang [Pathological Department of Henan Provincial People' s Hospital, Zhengzhou, Henan (China); Liu, Mingbo [Radiotherapeutical Department of Henan Provincial People' s Hospital, Zhengzhou, Henan (China)

    2017-12-15

    To determine the diagnostic value of monoexponential, biexponential and stretched exponential models for identifying lymph nodes (LNs) in patients with cervical cancer. Fifty female patients with cervical cancer underwent preoperative magnetic resonance imaging. The diffusion parameters of the LNs were calculated by fitting the values to monoexponential, biexponential and stretched exponential models and were compared between the metastatic and non-metastatic LN groups. A total of 157 LNs with high signal intensity on multi-b-value DWI were detected, 41 of which were pathologically shown to be metastatic. Metastatic LNs presented with higher pure water diffusion (D) values, lower perfusion fraction (f) values, higher diffusion heterogeneity (α) values, higher short diameter (Size-S), long diameter (Size-L) and short long diameter ratio (S/L Ratio) than non-metastatic LNs (P<0.05). The Size-S of LNs exhibited the highest diagnostic value, with an area under the curve of 0.844. Compared with the size parameters, the diffusion parameters derived from multi-b-value diffusion-weighted imaging cannot reliably discriminate metastatic from non-metastatic LNs in daily clinical routine due to limited sensitivity and specificity. (orig.)

  7. Outcomes of colon resection in patients with metastatic colon cancer.

    Science.gov (United States)

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

    2016-08-01

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

  8. Psychological interventions for women with non-metastatic breast cancer.

    Science.gov (United States)

    Jassim, Ghufran A; Whitford, David L; Hickey, Anne; Carter, Ben

    2015-05-28

    Breast cancer is the most common cancer affecting women worldwide. It is a distressing diagnosis and, as a result, considerable research has examined the psychological sequelae of being diagnosed and treated for breast cancer. Breast cancer is associated with increased rates of depression and anxiety and reduced quality of life. As a consequence, multiple studies have explored the impact of psychological interventions on the psychological distress experienced after a diagnosis of breast cancer. To assess the effects of psychological interventions on psychological morbidities, quality of life and survival among women with non-metastatic breast cancer. We searched the following databases up to 16 May 2013: the Cochrane Breast Cancer Group Specialised Register, CENTRAL, MEDLINE, EMBASE, CINAHL and PsycINFO; and reference lists of articles. We also searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) search portal and ClinicalTrials.gov for ongoing trials in addition to handsearching. Randomised controlled trials that assessed the effectiveness of psychological interventions for non-metastatic breast cancer in women. Two review authors independently appraised and extracted data from eligible trials. Any disagreement was resolved by discussion. Extracted data included information about participants, methods, the intervention and outcome. Twenty-eight randomised controlled trials comprising 3940 participants were included. The most frequent reasons for exclusion were non-randomised trials and the inclusion of women with metastatic disease. A wide range of interventions were evaluated, with 24 trials investigating a cognitive behavioural therapy and four trials investigating psychotherapy compared to control. Pooled standardised mean differences (SMD) from baseline indicated less depression (SMD -1.01, 95% confidence interval (CI) -1.83 to -0.18; P = 0.02; 7 studies, 637 participants, I(2) = 95%, low quality evidence), anxiety

  9. Utility of dysphagia grade in predicting endoscopic ultrasound T-stage of non-metastatic esophageal cancer.

    Science.gov (United States)

    Fang, T C; Oh, Y S; Szabo, A; Khan, A; Dua, K S

    2016-08-01

    Patients with non-metastatic esophageal cancer routinely undergo endoscopic ultrasound (EUS) for loco-regional staging. Neoadjuvant therapy is recommended for ≥T3 tumors while upfront surgery can be considered for ≤T2 lesions. The aim of this study was to determine if the degree of dysphagia can predict the EUS T-stage of esophageal cancer. One hundred eleven consecutive patients with non-metastatic esophageal cancer were retrospectively reviewed from a database. Prior to EUS, patients' dysphagia grade was recorded. Correlation between dysphagia grade and EUS T-stage, especially in reference to predicting ≥T3 stage, was determined. The correlation of dysphagia grade with EUS T-stage (Kendall's tau coefficient) was 0.49 (P dysphagia grade ≥2 (can only swallow semi-solids/liquids) for T3 cancer were 56% (95% confidence interval [CI] 43-67%) and 93% (95% CI 79-98%), respectively. The sensitivity, specificity, and positive predictive value of dysphagia grade ≥3 (can only swallow liquids or total dysphagia) for T3 lesions were 36% (95% CI 25-48%), 100% (95% CI 89-100%), and 100% (95% CI 83-100%), respectively. Overall, there was a significant positive correlation between dysphagia grade and the EUS T-stage of esophageal cancer. All patients with dysphagia grade ≥3 had T3 lesions. This may have clinical implications for patients who can only swallow liquids or have complete dysphagia by allowing for prompt initiation of neoadjuvant therapy, especially in countries/centers where EUS service is difficult to access in a timely manner or not available. © 2015 International Society for Diseases of the Esophagus.

  10. Vasohibin-1 suppresses colon cancer

    OpenAIRE

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

    2015-01-01

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

  11. Carotenoids and colon cancer.

    Science.gov (United States)

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

    2000-02-01

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

  12. Muscarinic Receptor Signaling in Colon Cancer

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-03-02

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

  13. Muscarinic Receptor Signaling in Colon Cancer

    International Nuclear Information System (INIS)

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

    2011-01-01

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

  14. Muscarinic Receptor Signaling in Colon Cancer

    Directory of Open Access Journals (Sweden)

    Jean-Pierre Raufman

    2011-03-01

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

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

    Directory of Open Access Journals (Sweden)

    Cheng M

    2014-12-01

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

  16. Vasohibin-1 suppresses colon cancer

    Science.gov (United States)

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

    2015-01-01

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

  17. Vasohibin-1 suppresses colon cancer.

    Science.gov (United States)

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

    2015-04-10

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

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

    Science.gov (United States)

    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

  19. Colon cancer screening

    Science.gov (United States)

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

  20. Radiotherapy in the management of non-metastatic prostate cancer: Current standards and future opportunities

    International Nuclear Information System (INIS)

    Forman, Jeffrey D.

    1997-01-01

    Objectives: The intent of this course is to review issues involved in the management of non-metastatic prostate cancer and to clarify the role of external beam radiotherapy, the use of neo-adjuvant and adjuvant hormonal therapy in conjunction with the radiation, the management of patients with regional metastases and recurrent disease following surgery and radiation. At the end of this course, participants should be able to fluently discuss management issues and strategies across the entire spectrum of non-metastatic prostate cancer. - Pre-treatment prognostic factors including clinical stage, grade, and pre-treatment PSA, will be presented and their relative value in determining therapeutic strategies will be discussed. Strategies to be discussed include standard dose radiation, escalated dose radiation, particle radiation and the use of adjuvant and neo-adjuvant hormonal therapy. - The process of simulation and field design will be presented, the value of CT-based treatment planning, beams-eye view design and the relative value of three-dimensional treatment planning will be discussed. - The significance of prostate and patient movement and strategies for dealing with this will also be presented so that what constitutes an adequate simulation and margin of treatment can be clarified. - The management of newly diagnosed patients, covering the range of low stage/low grade to locally advanced prostate cancer will be discussed. - The relative value of increasing dose, the relative value of using neo-adjuvant and/or adjuvant hormone therapy and the indications for escalated dose will be presented. - Strategies for managing post-prostatectomy patients will be reviewed. Data on adjuvant and therapeutic irradiation for biochemical failure will be presented and a strategy for management will be discussed. - How to deal with patients with residual disease post radiation will be discussed and the relative value of cryotherapy, salvage prostatectomy or hormonal therapy will

  1. Relationship between preoperative breast MRI and surgical treatment of non-metastatic breast cancer.

    Science.gov (United States)

    Onega, Tracy; Weiss, Julie E; Goodrich, Martha E; Zhu, Weiwei; DeMartini, Wendy B; Kerlikowske, Karla; Ozanne, Elissa; Tosteson, Anna N A; Henderson, Louise M; Buist, Diana S M; Wernli, Karen J; Herschorn, Sally D; Hotaling, Elise; O'Donoghue, Cristina; Hubbard, Rebecca

    2017-12-01

    More extensive surgical treatments for early stage breast cancer are increasing. The patterns of preoperative MRI overall and by stage for this trend has not been well established. Using Breast Cancer Surveillance Consortium registry data from 2010 through 2014, we identified women with an incident non-metastatic breast cancer and determined use of preoperative MRI and initial surgical treatment (mastectomy, with or without contralateral prophylactic mastectomy (CPM), reconstruction, and breast conserving surgery ± radiation). Clinical and sociodemographic covariates were included in multivariable logistic regression models to estimate adjusted odds ratios and 95% confidence intervals. Of the 13 097 women, 2217 (16.9%) had a preoperative MRI. Among the women with MRI, results indicated 32% higher odds of unilateral mastectomy compared to breast conserving surgery and of mastectomy with CPM compared to unilateral mastectomy. Women with preoperative MRI also had 56% higher odds of reconstruction. Preoperative MRI in women with DCIS and early stage invasive breast cancer is associated with more frequent mastectomy, CPM, and reconstruction surgical treatment. Use of more extensive surgical treatment and reconstruction among women with DCIS and early stage invasive cancer whom undergo MRI warrants further investigation. © 2017 Wiley Periodicals, Inc.

  2. Nutrients and Risk of Colon Cancer

    Directory of Open Access Journals (Sweden)

    Les Mery

    2010-02-01

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

  3. Nutrients and Risk of Colon Cancer

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-02-10

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

  4. Nutrients and Risk of Colon Cancer

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  5. Curative resection of transverse colon cancer via minilaparotomy.

    Science.gov (United States)

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

    2011-01-01

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

  6. Prostate radiation in non-metastatic castrate refractory prostate cancer provides an interesting insight into biology of prostate cancer

    Directory of Open Access Journals (Sweden)

    Pascoe Abigail C

    2012-03-01

    Full Text Available Abstract Background The natural history of non-metastatic castrate refractory prostate cancer is unknown and treatment options are limited. We present a retrospective review of 13 patients with locally advanced or high risk prostate cancer, initially treated with hormone monotherapy and then treated with prostate radiation after becoming castration refractory. Findings Median PSA response following prostate radiation was 67.4%. Median time to biochemical progression following radiotherapy was 15 months and to detection of metastatic disease was 18.5 months. Median survival from castration resistance (to date of death or November 2011 was 60 months, with median survival from RT 42 months. Conclusion Prostate radiation appears to be beneficial even in patients with potential micrometastatic disease, which supports the hypothesis that the primary tumour is important in the progression of prostate cancer. These results are an interesting addition to the literature on the biology of prostate cancer especially as this data is unlikely to be available in the future due to combined prostate radiation and androgen deprivation therapy now being the standard of care.

  7. [Non-metastatic clear cell renal cancer: dependence of the tumour stage on clinico-anatomic and morphologic factors; prognostic value of macro- and karyometric characteristics].

    Science.gov (United States)

    Iurin, A G

    2010-01-01

    Non-metastatic clear-cell renal cancer: dependence of the tumour stage on clinico-anatomic and morphologic factors; prognostic value of macro- and karyometric characteristics Sankt Peterburg Pathology Bureau, Sankt Peterburg It was shown based on multivariate regression analysis that pT1a3bN0MO stages of non-metastatic clear-cell renal cancer significantly correlate not only with the tumor size and invasion into the fatty tissue and/or renal vein but also with the invasion into the renal capsule and with the mean maximum diameter and mean nucleus area of tumor cells. There was no correlation of clear-cell renal cancer stages with tumor proliferative activity, gene p53 mutation, oncosuppressor gene PTEN expression, fraction of tumour clear-cell component, and such clinical characteristics as patients' sex, age, and body mass index. Taking into account statistically significant differences between the patients' survival rates, the regression equations developed in this work may be used for the prediction of disease outcome.

  8. CALCIUM AND THE PREVENTION OF COLON CANCER

    NARCIS (Netherlands)

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

    1991-01-01

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

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

    Science.gov (United States)

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

    2009-01-01

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

  10. Increased colon cancer risk after severe Salmonella infection.

    Directory of Open Access Journals (Sweden)

    Lapo Mughini-Gras

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

  11. Increased colon cancer risk after severe Salmonella infection

    Science.gov (United States)

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

    2018-01-01

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

  12. Endoscopic Localization of Colon Cancer Is Frequently Inaccurate.

    Science.gov (United States)

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

    2017-08-01

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

  13. A Case of Sigmoid Colon Tuberculosis Mimicking Colon Cancer

    OpenAIRE

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    McDougall Gordon

    2007-01-01

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

  15. Role of neutral ceramidase in colon cancer.

    Science.gov (United States)

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

    2016-12-01

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

  16. Increased diacylglycerol kinase ζ expression in human metastatic colon cancer cells augments Rho GTPase activity and contributes to enhanced invasion

    International Nuclear Information System (INIS)

    Cai, Kun; Mulatz, Kirk; Ard, Ryan; Nguyen, Thanh; Gee, Stephen H

    2014-01-01

    Unraveling the signaling pathways responsible for the establishment of a metastatic phenotype in carcinoma cells is critically important for understanding the pathology of cancer. The acquisition of cell motility is a key property of metastatic tumor cells and is a prerequisite for invasion. Rho GTPases regulate actin cytoskeleton reorganization and the cellular responses required for cell motility and invasion. Diacylglycerol kinase ζ (DGKζ), an enzyme that phosphorylates diacylglycerol to yield phosphatidic acid, regulates the activity of the Rho GTPases Rac1 and RhoA. DGKζ mRNA is highly expressed in several different colon cancer cell lines, as well as in colon cancer tissue relative to normal colonic epithelium, and thus may contribute to the metastatic process. To investigate potential roles of DGKζ in cancer metastasis, a cellular, isogenic model of human colorectal cancer metastatic transition was used. DGKζ protein levels, Rac1 and RhoA activity, and PAK phosphorylation were measured in the non-metastatic SW480 adenocarcinoma cell line and its highly metastatic variant, the SW620 line. The effect of DGKζ silencing on Rho GTPase activity and invasion through Matrigel-coated Transwell inserts was studied in SW620 cells. Invasiveness was also measured in PC-3 prostate cancer and MDA-MB-231 breast cancer cells depleted of DGKζ. DGKζ protein levels were elevated approximately 3-fold in SW620 cells compared to SW480 cells. There was a concomitant increase in active Rac1 in SW620 cells, as well as substantial increases in the expression and phosphorylation of the Rac1 effector PAK1. Similarly, RhoA activity and expression were increased in SW620 cells. Knockdown of DGKζ expression in SW620 cells by shRNA-mediated silencing significantly reduced Rac1 and RhoA activity and attenuated the invasiveness of SW620 cells in vitro. DGKζ silencing in highly metastatic MDA-MB-231 breast cancer cells and PC-3 prostate cancer cells also significantly attenuated

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

    Science.gov (United States)

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

    2015-09-01

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

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

    NARCIS (Netherlands)

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

    2016-01-01

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

  19. Radiation-associated colon cancer: A case report.

    Science.gov (United States)

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

    2017-06-01

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

  20. Colon and rectal cancer

    International Nuclear Information System (INIS)

    Saldombide, L.; Cordoba, A.

    2010-01-01

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

  1. Melanosis coli in patients with colon cancer

    Directory of Open Access Journals (Sweden)

    Dorota Biernacka-Wawrzonek

    2016-12-01

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

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

    OpenAIRE

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

    2009-01-01

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

  3. Prognostic impact of Metadherin-SND1 interaction in colon cancer.

    Science.gov (United States)

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

    2012-12-01

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

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

    Science.gov (United States)

    McGowan, Erin L; Prapavessis, Harry

    2010-12-01

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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2014-11-01

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

  7. Emergency management of acute colonic cancer obstruction.

    Science.gov (United States)

    Gainant, A

    2012-02-01

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

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

    Science.gov (United States)

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

    2018-03-01

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

  9. Enterobacter Strains Might Promote Colon Cancer.

    Science.gov (United States)

    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.

  10. Combinatorial nanomedicines for colon cancer therapy.

    Science.gov (United States)

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

    2016-01-01

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

  11. Directory of Colon and Rectal Cancer Specialist Teams

    OpenAIRE

    Department of Health; Social Services and Public Safety

    2004-01-01

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

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

    Science.gov (United States)

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

    2008-03-01

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

  13. Optical imaging of metabolic adaptability in metastatic and non-metastatic breast cancer

    Science.gov (United States)

    Rebello, Lisa; Rajaram, Narasimhan

    2018-02-01

    Accurate methods for determining metastatic risk from the primary tumor are crucial for patient survival. Cell metabolism could potentially be used as a marker of metastatic risk. Optical imaging of the endogenous fluorescent molecules nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) provides a non-destructive and label-free method for determining cell metabolism. The optical redox ratio (FAD/FAD+NADH) is sensitive to the balance between glycolysis and oxidative phosphorylation (OXPHOS). We have previously established that hypoxia-reoxygenation stress leads to metastatic potential-dependent changes in optical redox ratio. The objective of this study was to monitor the changes in optical redox ratio in breast cancer cells in response to different periods of hypoxic stress as well various levels of hypoxia to establish an optimal protocol. We measured the optical redox ratio of highly metastatic 4T1 murine breast cancer cells under normoxic conditions and after exposure to 30, 60, and 120 minutes of 0.5% O2. This was followed by an hour of reoxygenation. We found an increase in the optical redox ratio following reoxygenation from hypoxia for all durations. Statistically significant differences were observed at 60 and 120 minutes (p˂0.01) compared with normoxia, implying an ability to adapt to OXPHOS after reoxygenation. The switch to OXPHOS has been shown to be a key promoter of cell invasion. We will present our results from these investigations in human breast cancer cells as well as non-metastatic breast cancer cells exposed to various levels of hypoxia.

  14. Increased colon cancer risk after severe Salmonella infection

    OpenAIRE

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

    2018-01-01

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

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

    Science.gov (United States)

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

    2016-10-18

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

  16. Accuracy of colonoscopy in localizing colonic cancer.

    Science.gov (United States)

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

    2007-01-01

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

  17. Neoadjuvant chemotherapy in locally advanced colon cancer

    DEFF Research Database (Denmark)

    Jakobsen, Anders; Andersen, Fahimeh; Fischer, Anders

    2015-01-01

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

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

    Science.gov (United States)

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

  19. CT staging of colon cancer

    International Nuclear Information System (INIS)

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

    2008-01-01

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

  20. CT staging of colon cancer

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-12-15

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

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

    Science.gov (United States)

    Zhang, Xin; Zheng, Peng-sheng

    2010-02-01

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

  2. Gene Signature in Sessile Serrated Polyps Identifies Colon Cancer Subtype

    Science.gov (United States)

    Kanth, Priyanka; Bronner, Mary P.; Boucher, Kenneth M.; Burt, Randall W.; Neklason, Deborah W.; Hagedorn, Curt H.; Delker, Don A.

    2016-01-01

    Sessile serrated colon adenoma/polyps (SSA/Ps) are found during routine screening colonoscopy and may account for 20–30% of colon cancers. However, differentiating SSA/Ps from hyperplastic polyps (HP) with little risk of cancer is challenging and complementary molecular markers are needed. Additionally, the molecular mechanisms of colon cancer development from SSA/Ps are poorly understood. RNA sequencing was performed on 21 SSA/Ps, 10 HPs, 10 adenomas, 21 uninvolved colon and 20 control colon specimens. Differential expression and leave-one-out cross validation methods were used to define a unique gene signature of SSA/Ps. Our SSA/P gene signature was evaluated in colon cancer RNA-Seq data from The Cancer Genome Atlas (TCGA) to identify a subtype of colon cancers that may develop from SSA/Ps. A total of 1422 differentially expressed genes were found in SSA/Ps relative to controls. Serrated polyposis syndrome (n=12) and sporadic SSA/Ps (n=9) exhibited almost complete (96%) gene overlap. A 51-gene panel in SSA/P showed similar expression in a subset of TCGA colon cancers with high microsatellite instability (MSI-H). A smaller seven-gene panel showed high sensitivity and specificity in identifying BRAF mutant, CpG island methylator phenotype high (CIMP-H) and MLH1 silenced colon cancers. We describe a unique gene signature in SSA/Ps that identifies a subset of colon cancers likely to develop through the serrated pathway. These gene panels may be utilized for improved differentiation of SSA/Ps from HPs and provide insights into novel molecular pathways altered in colon cancer arising from the serrated pathway. PMID:27026680

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

    Science.gov (United States)

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

    2014-01-01

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

  4. Curcumin synergizes with resveratrol to inhibit colon cancer.

    Science.gov (United States)

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

    2009-01-01

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

  5. The Economics of Colon Cancer.

    Science.gov (United States)

    Orangio, Guy R

    2018-04-01

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

  6. Clinicopathologic factors identify sporadic mismatch repair-defective colon cancers

    DEFF Research Database (Denmark)

    Halvarsson, Britta; Anderson, Harald; Domanska, Katarina

    2008-01-01

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

  7. Colon Cancer After Acute Diverticulitis Treatment

    OpenAIRE

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

    2013-01-01

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

  8. Prostate and Colon Cancer Screening Messages in Popular Magazines

    Science.gov (United States)

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

    2004-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Palaniselvam Kuppusamy

    2014-06-01

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

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

    Science.gov (United States)

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

    2014-06-01

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

  11. Differences in telomerase activity between colon and rectal cancer.

    Science.gov (United States)

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

    2014-06-01

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

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

    OpenAIRE

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

    1996-01-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Gouda YG

    2016-01-01

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

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

    Science.gov (United States)

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

    2013-12-01

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

  16. Colon cancer chemoprevention with ginseng and other botanicals.

    OpenAIRE

    Wargovich, M J

    2001-01-01

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

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

    Science.gov (United States)

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

    2016-05-01

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

  18. Occlusive stenosis – atypical presentation of right colon cancer

    Directory of Open Access Journals (Sweden)

    Petrişor Banu

    2018-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Yen-Chien Lee

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

  20. EMT is the dominant program in human colon cancer

    Directory of Open Access Journals (Sweden)

    Tollenaar Rob AEM

    2011-01-01

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

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

    Science.gov (United States)

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

    2015-09-01

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

  2. Potentialities of computed tomography and ultrasonography in colonic cancer

    International Nuclear Information System (INIS)

    Gorshkov, A.N.

    2001-01-01

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

  3. Younger age is an independent predictor of worse prognosis among Lebanese nonmetastatic breast cancer patients: analysis of a prospective cohort

    Directory of Open Access Journals (Sweden)

    El Chediak A

    2017-06-01

    Full Text Available Alissar El Chediak,1 Raafat S Alameddine,1 Ayman Hakim,1 Lara Hilal,2 Sarah Abdel Massih,1 Lana Hamieh,3 Deborah Mukherji,1 Sally Temraz,1 Maya Charafeddine,1 Ali Shamseddine1 1Division of Hematology/Oncology, Department of Internal Medicine, 2Department of Radiation Oncology, American University of Beirut Medical Center, Beirut, Lebanon; 3Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Boston, MA, USA Background: Several retrospective studies have reported that younger age at presentation is associated with a worse prognosis for nonmetastatic breast cancer patients. In this study, we prospectively assessed the association between different baseline characteristics (age, tumor characteristics, mode of treatment, etc and outcomes among newly diagnosed nonmetastatic Lebanese breast cancer patients.Methods: We recruited a sample of 123 women newly diagnosed with nonmetastatic breast cancer presenting to American University of Beirut Medical Center. Immunohistochemical, molecular (vitamin D receptor, methylene tetrahydrofolate reductase polymorphisms, and genetic assays were performed. Patient characteristics were compared by age group (<40 and ≥40 years. A Cox regression analysis was performed to evaluate the variables affecting the disease-free survival (DFS. Outcome data were obtained, and DFS was estimated.Results: Among the 123 patients, 47 were 40 years of age or younger, and 76 were older than 40 years. Median follow-up duration was 58 months. Nine out of 47 patients <40 years (19.1% experienced disease relapse in contrast to four out of 76 patients >40 years (5.2%. A wide immunohistochemical panel included Ki-67, cyclin B1, p53, platelet-derived growth factor receptor, and vascular endothelial growth factor receptor, and did not reveal any significant difference in these markers between the two age groups. Older patients had a larger percentage of Luminal A than younger patients. On multivariate analysis

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

    Directory of Open Access Journals (Sweden)

    Huihong Zhai

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

  5. Mechanisms of oncogenesis in colon versus rectal cancer.

    NARCIS (Netherlands)

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

    2001-01-01

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

  6. Transverse colon cancer with Krukenberg tumor : A case report

    OpenAIRE

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

    1999-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Justin Y Jeon

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

  8. Local staging of sigmoid colon cancer using MRI

    DEFF Research Database (Denmark)

    Dam, Claus; Lindebjerg, Jan; Jakobsen, Anders

    2017-01-01

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

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

    Science.gov (United States)

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

    2014-05-21

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

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

    Science.gov (United States)

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

    2017-01-01

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

  11. Multifaceted Interpretation of Colon Cancer Stem Cells.

    Science.gov (United States)

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

    2017-07-05

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

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

    Science.gov (United States)

    Soto-Ortiz, Luis; Brody, James P

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Luis Soto-Ortiz

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

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

    Science.gov (United States)

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

    2016-09-16

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

  15. Combination of capecitabine and ludartin inhibits colon cancer ...

    African Journals Online (AJOL)

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

  16. Colonic macrophage polarization in homeostasis, inflammation, and cancer

    Science.gov (United States)

    Appleyard, Caroline B.

    2016-01-01

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

  17. Early colon cancer : findings on double contrast barium enema

    International Nuclear Information System (INIS)

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

    1998-01-01

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

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

    Science.gov (United States)

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

    2014-10-14

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

  19. Screening for colorectal cancer in defunctioned colons.

    Science.gov (United States)

    Akbar, Fayyaz; Quyn, Aaron; Steele, Robert

    2018-01-01

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

  20. Microchimerism and survival after breast and colon cancer diagnosis

    DEFF Research Database (Denmark)

    Kamper-Jørgensen, Mads

    2012-01-01

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

  1. A Prospective Evaluation of Plasma Polyphenol Levels and Colon Cancer Risk

    DEFF Research Database (Denmark)

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

    2018-01-01

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

  2. Immunohistochemical study of p53 overexpression in radiation-induced colon cancers

    International Nuclear Information System (INIS)

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

    1998-01-01

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

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

    OpenAIRE

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

    2014-01-01

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

  4. Colon Cancer Risk Assessment - Gauss Program

    Science.gov (United States)

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

  5. Immunoreactivities of human nonmetastatic clone 23 and p53 products are disassociated and not good predictors of lymph node metastases in early-stage cervical cancer patients.

    Science.gov (United States)

    Tee, Y T; Wang, P H; Ko, J L; Chen, G D; Chang, H; Lin, L Y

    2007-01-01

    To assess the relation between expressions of human nonmetastatic clone 23 (nm23-H1) and p53 in cervical cancer, their relationships with lymph node metastasis, and further to examine their predictive of lymph node metastases. nm23-H1 and p53 expression profiles were visualized by immunohistochemistry in early-stage cervical cancer specimens. Immunoreactivities of nm23-H1 and p53 were disassociated. The independent variables related with lymph node metastases were grade of cancer cell differentiation (p not good predictors of lymph node metastases in early-stage cervical cancer patients. However, stromal invasion and cell differentiation can predict lymph node metastasis.

  6. Combination of capecitabine and ludartin inhibits colon cancer ...

    African Journals Online (AJOL)

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

  7. Clinicopathologic factors identify sporadic mismatch repair-defective colon cancers

    DEFF Research Database (Denmark)

    Halvarsson, Britta; Anderson, Harald; Domanska, Katarina

    2008-01-01

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

  8. Bladder preservation in non-metastatic muscle-invasive bladder cancer (MIBC): a single-institution experience.

    Science.gov (United States)

    Gerardi, Marianna A; Jereczek-Fossa, Barbara A; Zerini, Dario; Surgo, Alessia; Dicuonzo, Samantha; Spoto, Ruggero; Fodor, Cristiana; Verri, Elena; Rocca, Maria Cossu; Nolè, Franco; Muto, Matteo; Ferro, Matteo; Musi, Gennaro; Bottero, Danilo; Matei, Deliu V; De Cobelli, Ottavio; Orecchia, Roberto

    2016-01-01

    The aim of this study is to access the feasibility, toxicity profile, and tumour outcome of an organ preservation curative approach in non-metastatic muscle-invasive bladder cancer. A retrospective analysis was conducted on patients affected by M0 bladder cancer, who refused cystectomy and were treated with a curative approach. The standard bladder preservation scheme included maximal transurethral resection of bladder tumour (TURBT) and combination of radiotherapy and platin-based chemotherapy, followed by endoscopic evaluation, urine cytology, and instrumental evaluation. Thirteen patients fulfilled the inclusion criteria. TNM stage was cT2cN0M0 and cT2cNxM0, in 12 and one patients, respectively. All patients had transitional cell cancer. Twelve patients completed the whole therapeutic programme (a bimodal treatment without chemotherapy for one patient). Median follow-up is 36 months. None of the patients developed severe urinary or intestinal acute toxicity. In 10 patients with a follow-up > 6 months, no cases of severe late toxicity were observed. Response evaluated in 12 patients included complete response and stable disease in 11 patients (92%), and one patient (8%), respectively. At the time of data analysis (March 2016), 10 patients (77%) are alive with no evidence of disease, two patients (15%) died for other reasons, and one patient has suspicious persistent local disease. The trimodality approach, including maximal TURBT, radiotherapy, and chemotherapy for muscle-invasive bladder cancer, is well-tolerated and might be considered a valid and feasible option in fit patients who refuse radical cystectomy.

  9. Red meat and colon cancer : a possible role for heme

    NARCIS (Netherlands)

    Sesink, Aloysius Lambertus Antonia

    2000-01-01

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

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

    Science.gov (United States)

    2015-04-27

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

  11. Lycopene, tomato products and prostate cancer-specific mortality among men diagnosed with nonmetastatic prostate cancer in the Cancer Prevention Study II Nutrition Cohort.

    Science.gov (United States)

    Wang, Ying; Jacobs, Eric J; Newton, Christina C; McCullough, Marjorie L

    2016-06-15

    While dietary lycopene and tomato products have been inversely associated with prostate cancer incidence, there is limited evidence for an association between consumption of lycopene and tomato products and prostate-cancer specific mortality (PCSM). We examined the associations of prediagnosis and postdiagnosis dietary lycopene and tomato product intake with PCSM in a large prospective cohort. This analysis included men diagnosed with nonmetastatic prostate cancer between enrollment in the Cancer Prevention Study II Nutrition Cohort in 1992 or 1993 and June 2011. Prediagnosis dietary data, collected at baseline, were available for 8,898 men, of whom 526 died of prostate cancer through 2012. Postdiagnosis dietary data, collected on follow-up surveys in 1999 and/or 2003, were available for 5,643 men, of whom 363 died of prostate cancer through 2012. Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for PCSM. Neither prediagnosis nor postdiagnosis dietary lycopene intake was associated with PCSM (fourth vs. first quartile HR = 1.00, 95% CI 0.78-1.28; HR = 1.22, 95% CI 0.91-1.64, respectively). Similarly, neither prediagnosis nor postdiagnosis consumption of tomato products was associated with PCSM. Among men with high-risk cancers (T3-T4 or Gleason score 8-10, or nodal involvement), consistently reporting lycopene intake ≥ median on both postdiagnosis surveys was associated with lower PCSM (HR = 0.41, 95% CI 0.17-0.99, based on ten PCSM cases consistently ≥ median intake) compared to consistently reporting intake lycopene intake with PCSM among men with high-risk prostate cancers. © 2016 UICC.

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

    Science.gov (United States)

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

    2008-07-01

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

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

    Science.gov (United States)

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

    2000-01-01

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

  14. Bicalutamide 150 mg in addition to standard care for patients with early non-metastatic prostate cancer: updated results from the Scandinavian Prostate Cancer Period Group-6 Study after a median follow-up period of 7.1 years

    DEFF Research Database (Denmark)

    Iversen, Peter; Johansson, Jan-Erik; Lodding, Pär

    2006-01-01

    The Early Prostate Cancer (EPC) programme is evaluating the efficacy and tolerability of bicalutamide following standard care (radiotherapy, radical prostatectomy or watchful waiting) in patients with localized (T1-2, N0/Nx) or locally advanced (T3-4, any N; or any T, N + ) non-metastatic prostat...

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

    Science.gov (United States)

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

    2014-05-13

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2014-05-01

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

  18. Pitfalls in diagnosing colon cancer on abdominal CT.

    Science.gov (United States)

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

    2017-10-01

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

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

    Science.gov (United States)

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

    2016-03-01

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

  20. Increasing Use of Dose-Escalated External Beam Radiation Therapy for Men With Nonmetastatic Prostate Cancer

    International Nuclear Information System (INIS)

    Swisher-McClure, Samuel; Mitra, Nandita; Woo, Kaitlin; Smaldone, Marc; Uzzo, Robert; Bekelman, Justin E.

    2014-01-01

    Purpose: To examine recent practice patterns, using a large national cancer registry, to understand the extent to which dose-escalated external beam radiation therapy (EBRT) has been incorporated into routine clinical practice for men with prostate cancer. Methods and Materials: We conducted a retrospective observational cohort study using the National Cancer Data Base, a nationwide oncology outcomes database in the United States. We identified 98,755 men diagnosed with nonmetastatic prostate cancer between 2006 and 2011 who received definitive EBRT and classified patients into National Comprehensive Cancer Network (NCCN) risk groups. We defined dose-escalated EBRT as total prescribed dose of ≥75.6 Gy. Using multivariable logistic regression, we examined the association of patient, clinical, and demographic characteristics with the use of dose-escalated EBRT. Results: Overall, 81.6% of men received dose-escalated EBRT during the study period. The use of dose-escalated EBRT did not vary substantially by NCCN risk group. Use of dose-escalated EBRT increased from 70.7% of patients receiving treatment in 2006 to 89.8% of patients receiving treatment in 2011. On multivariable analysis, year of diagnosis and use of intensity modulated radiation therapy were significantly associated with receipt of dose-escalated EBRT. Conclusions: Our study results indicate that dose-escalated EBRT has been widely adopted by radiation oncologists treating prostate cancer in the United States. The proportion of patients receiving dose-escalated EBRT increased nearly 20% between 2006 and 2011. We observed high utilization rates of dose-escalated EBRT within all disease risk groups. Adoption of intensity modulated radiation therapy was strongly associated with use of dose-escalated treatment

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

    Lifescience Database Archive (English)

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

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

    Lifescience Database Archive (English)

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

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

    Lifescience Database Archive (English)

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

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

    Lifescience Database Archive (English)

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

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

    Science.gov (United States)

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

    2014-04-01

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

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

    Science.gov (United States)

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

    2013-11-01

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

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

    Science.gov (United States)

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

    2017-10-20

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

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

    Science.gov (United States)

    Cesaroni, Matteo; Powell, Jasmine; Sapienza, Carmen

    2014-07-01

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

  9. Drugs Approved for Colon and Rectal Cancer

    Science.gov (United States)

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

  10. Outcome of Laparoscopic Versus Open Resection for Transverse Colon Cancer.

    Science.gov (United States)

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

    2015-10-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2013-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Murray B. Gordon

    2016-01-01

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

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

    Lifescience Database Archive (English)

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

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

    Lifescience Database Archive (English)

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

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

    Lifescience Database Archive (English)

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

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

    Lifescience Database Archive (English)

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

  18. Preventing Second Cancers in Colon Cancer Survivors

    Science.gov (United States)

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

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

    Science.gov (United States)

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

    2015-06-01

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

  20. Survival after elective surgery for colonic cancer in Denmark

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2016-01-19

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

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

    Science.gov (United States)

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

    2004-06-01

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

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

    Science.gov (United States)

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

    2017-08-01

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

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

    Science.gov (United States)

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

    2013-02-15

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

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

    Science.gov (United States)

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

    2015-03-16

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

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

    Science.gov (United States)

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

    2014-01-01

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

  7. STUDY ON ADHERENCE TO CAPECITABINE AMONG PATIENTS WITH COLORECTAL CANCER AND METASTATIC BREAST CANCER

    Directory of Open Access Journals (Sweden)

    Adiel Goes de FIGUEIREDO JUNIOR

    2014-09-01

    Full Text Available Context Capecitabine, an oral drug, is as effective as traditional chemotherapy drugs. Objectives To investigate the adhesion to treatment with oral capecitabine in breast and colorectal cancer, and to determine any correlation with changes in patient’s quality of life. Methods Patients with colorectal cancer or breast cancer using capecitabine were included. The patients were asked to bring any medication left at the time of scheduled visits. The QLQ-C30 questionnaire was applied at the first visit and 8-12 weeks after treatment. Results Thirty patients were evaluated. Adherence was 88.3% for metastatic colon cancer, 90.4% for non-metastatic colon cancer, 94.3% for rectal cancer and 96.2% for metastatic breast cancer. No strong correlation between adherence and European Organisation for Research and Treatment of Cancer QLQ-C30 functional or symptom scale rates had been found. There was no statistically significant correlation between compliance and the functional and symptom scales of the questionnaire before and after chemotherapy, with the exception of dyspnea. Conclusions Although no absolute adherence to oral capecitabine treatment had been observed, the level of adherence was good. Health professionals therefore need a greater focus in the monitoring the involvement of patients with oral treatment regimens. Patients with lesser degrees of dyspnea had greater compliance.

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

    Science.gov (United States)

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

    2016-06-01

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

  9. Use of nonsteroidal antiinflamatory drugs for chemoprevention of colon cancer

    Directory of Open Access Journals (Sweden)

    Milić Aleksandra

    2013-01-01

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

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

    African Journals Online (AJOL)

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

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

    Directory of Open Access Journals (Sweden)

    Cheryl L Thompson

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

  12. miR-200–containing extracellular vesicles promote breast cancer cell metastasis

    Science.gov (United States)

    Le, Minh T.N.; Hamar, Peter; Guo, Changying; Basar, Emre; Perdigão-Henriques, Ricardo; Balaj, Leonora; Lieberman, Judy

    2014-01-01

    Metastasis is associated with poor prognosis in breast cancer patients. Not all cancer cells within a tumor are capable of metastasizing. The microRNA-200 (miR-200) family, which regulates the mesenchymal-to-epithelial transition, is enriched in the serum of patients with metastatic cancers. Ectopic expression of miR-200 can confer metastatic ability to poorly metastatic tumor cells in some settings. Here, we investigated whether metastatic capability could be transferred between metastatic and nonmetastatic cancer cells via extracellular vesicles. miR-200 was secreted in extracellular vesicles from metastatic murine and human breast cancer cell lines, and miR-200 levels were increased in sera of mice bearing metastatic tumors. In culture, murine and human metastatic breast cancer cell extracellular vesicles transferred miR-200 microRNAs to nonmetastatic cells, altering gene expression and promoting mesenchymal-to-epithelial transition. In murine cancer and human xenograft models, miR-200–expressing tumors and extracellular vesicles from these tumors promoted metastasis of otherwise weakly metastatic cells either nearby or at distant sites and conferred to these cells the ability to colonize distant tissues in a miR-200–dependent manner. Together, our results demonstrate that metastatic capability can be transferred by the uptake of extracellular vesicles. PMID:25401471

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

    Science.gov (United States)

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

    2017-08-01

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

  14. Current management of liver metastases of colon cancer

    International Nuclear Information System (INIS)

    Mainieri Breedy, Giovanna

    2010-01-01

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

  15. Clinical issues in the surgical treatment of colon cancer

    NARCIS (Netherlands)

    Amri, R.

    2015-01-01

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

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

    Science.gov (United States)

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

    2011-09-01

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

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  18. Eating patterns and risk of colon cancer.

    Science.gov (United States)

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

    1998-07-01

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

  19. PGE2-induced colon cancer growth is mediated by mTORC1

    International Nuclear Information System (INIS)

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

    2014-01-01

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

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

    Science.gov (United States)

    2015-09-10

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

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

    Science.gov (United States)

    Cesaroni, Matteo; Powell, Jasmine; Sapienza, Carmen

    2014-01-01

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

  2. Role of phytochemicals in colon cancer prevention. A nutrigenomics approach

    NARCIS (Netherlands)

    Erk, van M.J.

    2004-01-01

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

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

    Science.gov (United States)

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

    2015-09-29

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

  4. Cryptogenic pyogenic liver abscess as the herald of colon cancer.

    Science.gov (United States)

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

    2012-02-01

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

  5. Short-term outcomes following laparoscopic resection for colon cancer.

    LENUS (Irish Health Repository)

    Kavanagh, Dara O

    2011-03-01

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

  6. Activin and TGFβ use diverging mitogenic signaling in advanced colon cancer

    OpenAIRE

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2014-02-01

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

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

    Science.gov (United States)

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

    2013-05-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-11-18

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

  13. Pancreatoduodenectomy with colon resection for cancer: A nationwide retrospective analysis

    NARCIS (Netherlands)

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

    2016-01-01

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

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

    Lifescience Database Archive (English)

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

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

    Lifescience Database Archive (English)

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

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

    Lifescience Database Archive (English)

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

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

    Lifescience Database Archive (English)

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

  18. Predicting opportunities to increase utilization of laparoscopy for colon cancer.

    Science.gov (United States)

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

    2017-04-01

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

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

    Science.gov (United States)

    Kim, EuiJoo

    2017-01-01

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

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

    OpenAIRE

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

    2014-01-01

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

  1. Synchronous Adenocarcinoma of the Colon and Rectal Carcinoid

    Directory of Open Access Journals (Sweden)

    Vamshidhar Vootla

    2016-10-01

    Full Text Available Primary colonic adenocarcinoma and synchronous rectal carcinoids are rare tumors. Whenever a synchronous tumor with a nonmetastatic carcinoid component is encountered, its prognosis is determined by the associate malignancy. The discovery of an asymptomatic gastrointestinal carcinoid during the operative treatment of another malignancy will usually only require resection without additional treatment and will have little effect on the prognosis of the individual. This article reports a synchronous rectal carcinoid in a patient with hepatic flexure adenocarcinoma. We present a case of a 46-year-old Hispanic woman with a history of hypothyroidism, uterine fibroids and hypercholesterolemia presenting with a 2-week history of intermittent abdominal pain, mainly in the right upper quadrant. She had no family history of cancers. Physical examination was significant for pallor. Laboratory findings showed microcytic anemia with a hemoglobin of 6.6 g/dl. CT abdomen showed circumferential wall thickening in the ascending colon near the hepatic flexure and pulmonary nodules. Colonoscopy showed hepatic flexure mass and rectal nodule which were biopsied. Pathology showed a moderately differentiated invasive adenocarcinoma of the colon (hepatic flexure mass and a low-grade neuroendocrine neoplasm (carcinoid of rectum. The patient underwent laparoscopic right hemicolectomy and chemotherapy. In patients diagnosed with adenocarcinoma of the colon and rectum, carcinoids could be missed due to their submucosal location, multicentricity and indolent growth pattern. Studies suggest a closer surveillance of the GI tract for noncarcinoid synchronous malignancy when a carcinoid tumor is detected and vice versa.

  2. Understanding your colon cancer risk

    Science.gov (United States)

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

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

    Science.gov (United States)

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

    2010-03-01

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

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

    Science.gov (United States)

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

    2015-08-05

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

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

    NARCIS (Netherlands)

    Vogel, de J.

    2006-01-01

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

  6. Analysis on misdiagnosed cases of right colon cancer as appendicitis

    Directory of Open Access Journals (Sweden)

    Sijia Liu

    2016-08-01

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

  7. CIMP status of interval colon cancers: another piece to the puzzle.

    Science.gov (United States)

    Arain, Mustafa A; Sawhney, Mandeep; Sheikh, Shehla; Anway, Ruth; Thyagarajan, Bharat; Bond, John H; Shaukat, Aasma

    2010-05-01

    Colon cancers diagnosed in the interval after a complete colonoscopy may occur due to limitations of colonoscopy or due to the development of new tumors, possibly reflecting molecular and environmental differences in tumorigenesis resulting in rapid tumor growth. In a previous study from our group, interval cancers (colon cancers diagnosed within 5 years of a complete colonoscopy) were almost four times more likely to demonstrate microsatellite instability (MSI) than non-interval cancers. In this study we extended our molecular analysis to compare the CpG island methylator phenotype (CIMP) status of interval and non-interval colorectal cancers and investigate the relationship between the CIMP and MSI pathways in the pathogenesis of interval cancers. We searched our institution's cancer registry for interval cancers, defined as colon cancers that developed within 5 years of a complete colonoscopy. These were frequency matched in a 1:2 ratio by age and sex to patients with non-interval cancers (defined as colon cancers diagnosed on a patient's first recorded colonoscopy). Archived cancer specimens for all subjects were retrieved and tested for CIMP gene markers. The MSI status of subjects identified between 1989 and 2004 was known from our previous study. Tissue specimens of newly identified cases and controls (between 2005 and 2006) were tested for MSI. There were 1,323 cases of colon cancer diagnosed over the 17-year study period, of which 63 were identified as having interval cancer and matched to 131 subjects with non-interval cancer. Study subjects were almost all Caucasian men. CIMP was present in 57% of interval cancers compared to 33% of non-interval cancers (P=0.004). As shown previously, interval cancers were more likely than non-interval cancers to occur in the proximal colon (63% vs. 39%; P=0.002), and have MSI 29% vs. 11%, P=0.004). In multivariable logistic regression model, proximal location (odds ratio (OR) 1.85; 95% confidence interval (CI) 1

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

    OpenAIRE

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2008-09-01

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

  10. Cancer of the colon spleen angle. Presentation of a case

    International Nuclear Information System (INIS)

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

    2010-01-01

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

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

    LENUS (Irish Health Repository)

    Rogers, Ailín C

    2012-03-01

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

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

    Science.gov (United States)

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

    2017-10-01

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

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

    Science.gov (United States)

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

    2016-06-18

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

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  16. Locally advanced colon cancer with cutaneous invasion: case report.

    Science.gov (United States)

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

    2017-03-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2002-07-01

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

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

    International Nuclear Information System (INIS)

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

    2002-01-01

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

  19. Reproductive and hormonal factors in male and female colon cancer

    NARCIS (Netherlands)

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

    1994-01-01

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

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

    Science.gov (United States)

    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.

  1. Circulating Tumor Cell Count Correlates with Colorectal Neoplasm Progression and Is a Prognostic Marker for Distant Metastasis in Non-Metastatic Patients

    Science.gov (United States)

    Tsai, Wen-Sy; Chen, Jinn-Shiun; Shao, Hung-Jen; Wu, Jen-Chia; Lai-Ming, Jr.; Lu, Si-Hong; Hung, Tsung-Fu; Chiu, Yen-Chi; You, Jeng-Fu; Hsieh, Pao-Shiu; Yeh, Chien-Yuh; Hung, Hsin-Yuan; Chiang, Sum-Fu; Lin, Geng-Ping; Tang, Reiping; Chang, Ying-Chih

    2016-04-01

    Enumeration of circulating tumor cells (CTCs) has been proven as a prognostic marker for metastatic colorectal cancer (m-CRC) patients. However, the currently available techniques for capturing and enumerating CTCs lack of required sensitivity to be applicable as a prognostic marker for non-metastatic patients as CTCs are even more rare. We have developed a microfluidic device utilizing antibody-conjugated non-fouling coating to eliminate nonspecific binding and to promote the multivalent binding of target cells. We then established the correlation of CTC counts and neoplasm progression through applying this platform to capture and enumerate CTCs in 2 mL of peripheral blood from healthy (n = 27), benign (n = 21), non-metastatic (n = 95), and m-CRC (n = 15) patients. The results showed that the CTC counts progressed from 0, 1, 5, to 36. Importantly, after 2-year follow-up on the non-metastatic CRC patients, we found that those who had ≥5 CTCs were 8 times more likely to develop distant metastasis within one year after curable surgery than those who had marker for the non-metastatic CRC patients who are at high risk of early recurrence.

  2. Prognostic and predictive potential molecular biomarkers in colon cancer.

    Science.gov (United States)

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

    2011-01-01

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

  3. Symptoms and Impacts in Non-Metastatic Castration-Resistant Prostate Cancer: Qualitative Study Findings.

    Science.gov (United States)

    Tomaszewski, Erin L; Moise, Pierre; Krupnick, Robert N; Downing, Jared; Meyer, Margaret; Naidoo, Shevani; Holmstrom, Stefan

    2017-10-01

    We developed a conceptual model to define key concepts associated with patients' experiences with the signs, symptoms, and impacts of non-metastatic castration-resistant prostate cancer (M0-CRPC). A targeted review of peer-reviewed literature, and other publicly available information, identified and categorized symptoms and impacts related to early-stage prostate cancer. Semi-structured interviews with five clinical experts helped determine the most relevant and important concepts for patients with M0-CRPC. Qualitative interviews with 17 patients with M0-CRPC identified the most frequently experienced symptoms and impacts, and their degree of interference with patients' lives. The findings from these three lines of evidence were summarized in a conceptual model. Literature searches identified mainly urinary, intestinal, and sexual symptoms. Experts noted the symptoms most frequently mentioned by patients include erectile dysfunction, loss of sexual desire or interest, incontinence/leaking, urgency, and hot flashes. Patient interviews confirmed the high frequency of erectile dysfunction, loss of libido, urinary urgency, and incontinence. The most frequently mentioned impacts expressed by patients were the need to monitor/plan for urinary frequency, interference with/restriction of daily activities, and frustration or anxiety over diagnosis, symptoms, or treatment. Symptoms and impacts most frequently experienced by patients were typically not those with the greatest effects on their lives; rather, those with the greatest consequences were related to treatment. The leading concerns associated with M0-CRPC were related to voiding and sexual dysfunction. The most relevant symptoms and impacts expressed by patients may be a consequence of therapy rather than of the disease.

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

    African Journals Online (AJOL)

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

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

    Directory of Open Access Journals (Sweden)

    Nobu Oshima

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

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

    Science.gov (United States)

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

    2018-01-01

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

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

    Science.gov (United States)

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

    2017-06-25

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

  8. MicroRNAs as Regulator of Signaling Networks in Metastatic Colon Cancer

    Science.gov (United States)

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

    2015-01-01

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

  9. MicroRNAs as Regulator of Signaling Networks in Metastatic Colon Cancer.

    Science.gov (United States)

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

    2015-01-01

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

  10. MicroRNAs as Regulator of Signaling Networks in Metastatic Colon Cancer

    Directory of Open Access Journals (Sweden)

    Jian Wang

    2015-01-01

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

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

    Science.gov (United States)

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

    2017-03-01

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

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

    Science.gov (United States)

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

    2017-05-25

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

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

    Science.gov (United States)

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

    2006-05-01

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

  14. Right colon cancer: Left behind.

    Science.gov (United States)

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

    2016-09-01

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

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

    Science.gov (United States)

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

    2012-04-01

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

  16. Excess mortality after curative surgery for colorectal cancer changes over time and differs for patients with colon versus rectal cancer.

    Science.gov (United States)

    Nedrebø, Bjørn Steinar; Søreide, Kjetil; Eriksen, Morten Tandberg; Kvaløy, Jan Terje; Søreide, Jon Arne; Kørner, Hartwig

    2013-06-01

    Improved management of colorectal cancer patients has resulted in better five-year survival for rectal cancer compared with colon cancer. We compared excess mortality rates in various time intervals after surgery in patients with colon and rectal cancer. We analysed all patients with curative resection of colorectal cancers reported in the Cancer Registry of Norway before (1994-1996) and after (2001-2003) national treatment guidelines were introduced. Excess mortality was analysed in different postoperative time intervals within the five-year follow-up periods for patients treated in 1994-1996 vs. 2001-2003. A total of 11 437 patients that underwent curative resection were included. For patients treated from 1994 to 1996, excess mortality was similar in colon and rectal cancer patients in all time intervals. For those treated from 2001 to 2003, excess mortality was significantly lower in rectal cancer patients than in colon cancer patients perioperatively (in the first 60 days: excess mortality ratio = 0.46, p = 0.007) and during the first two postoperative years (2-12 months: excess mortality ratio = 0.54, p = 0.010; 1-2 years: excess mortality ratio = 0.60, p = 0.009). Excess mortality in rectal cancer patients was significantly greater than in colon cancer patients 4-5 years postoperatively (excess mortality ratio = 2.18, p = 0.003). Excess mortality for colon and rectal cancer changed substantially after the introduction of national treatment guidelines. Short-term excess mortality rates was higher in colon cancer compared to rectal cancer for patients treated in 2001-2003, while excess mortality rates for rectal cancer patients was significantly higher later in the follow-up period. This suggests that future research should focus on these differences of excess mortality in patients curatively treated for cancer of the colon and rectum.

  17. Deficient expression of DNA repair enzymes in early progression to sporadic colon cancer

    Science.gov (United States)

    2012-01-01

    Background Cancers often arise within an area of cells (e.g. an epithelial patch) that is predisposed to the development of cancer, i.e. a "field of cancerization" or "field defect." Sporadic colon cancer is characterized by an elevated mutation rate and genomic instability. If a field defect were deficient in DNA repair, DNA damages would tend to escape repair and give rise to carcinogenic mutations. Purpose To determine whether reduced expression of DNA repair proteins Pms2, Ercc1 and Xpf (pairing partner of Ercc1) are early steps in progression to colon cancer. Results Tissue biopsies were taken during colonoscopies of 77 patients at 4 different risk levels for colon cancer, including 19 patients who had never had colonic neoplasia (who served as controls). In addition, 158 tissue samples were taken from tissues near or within colon cancers removed by resection and 16 tissue samples were taken near tubulovillous adenomas (TVAs) removed by resection. 568 triplicate tissue sections (a total of 1,704 tissue sections) from these tissue samples were evaluated by immunohistochemistry for 4 DNA repair proteins. Substantially reduced protein expression of Pms2, Ercc1 and Xpf occurred in field defects of up to 10 cm longitudinally distant from colon cancers or TVAs and within colon cancers. Expression of another DNA repair protein, Ku86, was infrequently reduced in these areas. When Pms2, Ercc1 or Xpf were reduced in protein expression, then either one or both of the other two proteins most often had reduced protein expression as well. The mean inner colon circumferences, from 32 resections, of the ascending, transverse and descending/sigmoid areas were measured as 6.6 cm, 5.8 cm and 6.3 cm, respectively. When combined with other measurements in the literature, this indicates the approximate mean number of colonic crypts in humans is 10 million. Conclusions The substantial deficiencies in protein expression of DNA repair proteins Pms2, Ercc1 and Xpf in about 1 million

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

    International Nuclear Information System (INIS)

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

    2012-01-01

    Highlights: ► Nanog is expressed in a majority of colon cancer cell lines examined. ► Both nanog1 and nanogp8 are expressed in colon cancer cells with varying ratios. ► Nanog mediates cell proliferation of colon cancer cells. ► 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Ishiguro, Tatsuya; Sato, Ai; Ohata, Hirokazu; Sakai, Hiroaki [Division of Cancer Differentiation, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Nakagama, Hitoshi, E-mail: hnakagam@ncc.go.jp [Division of Cancer Development System, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Okamoto, Koji, E-mail: kojokamo@ncc.go.jo [Division of Cancer Differentiation, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan)

    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.

  20. Anxiety and its time courses during radiotherapy for non-metastatic breast cancer: A longitudinal study

    International Nuclear Information System (INIS)

    Lewis, Florence; Merckaert, Isabelle; Liénard, Aurore; Libert, Yves; Etienne, Anne-Marie; Reynaert, Christine; Slachmuylder, Jean-Louis; Scalliet, Pierre; Paul, Van Houtte; Coucke, Philippe

    2014-01-01

    Purpose: To our knowledge, no study has specifically assessed the time course of anxiety during radiotherapy (RT). The objective of this study was to assess anxiety time courses in patients with non-metastatic breast cancer. Material and methods: This multicenter, descriptive longitudinal study included 213 consecutive patients with breast cancer who completed visual analog scales (VASs) assessing state anxiety before and after the RT simulation and the first and last five RT sessions. Results: Pre- and post-session anxiety mean levels were highest at the RT simulation (respectively, 2.9 ± 2.9 and 1.6 ± 2.5) and first RT session (respectively, 3.4 ± 2.9 and 2.0 ± 2.4), then declined rapidly. Clinically relevant mean differences (⩾1 cm on the VAS) between pre- and post-simulation/session VAS scores were found only for the RT simulation (−1.3 ± 2.7; p < 0.001) and first RT session (−1.4 ± 2.4; p < 0.001). Five percent to 16% of patients presented clinically relevant anxiety (pre- and post-simulation/session VAS scores ⩾ 4 cm) throughout treatment. Conclusions: To optimize care, RT team members should offer all patients appropriate information about treatment at the simulation, check patients’ understanding, and identify patients with clinically relevant anxiety requiring appropriate support throughout RT

  1. Control of Colon Cancer Progression by the Colon Microbiome

    Science.gov (United States)

    2015-08-01

    Award  Number:    W81XWH-­14-­1-­0235   TITLE:      Control of Colon Cancer Progression by the Colon Microbiome PRINCIPAL  INVESTIGATOR:    Frank  J... Microbiome Table  of  Contents   Page   1. Introduction………………………………………………………….4 2. Keywords…………………………………………………………….5 3. Accomplishments………..…………………………………………5

  2. [Treatment reality with respect to laparoscopic surgery of colonic cancer in Germany].

    Science.gov (United States)

    Ptok, H; Gastinger, I; Bruns, C; Lippert, H

    2014-07-01

    Prospective randomized studies and meta-analyses have shown that laparoscopic resection for colonic cancer is equivalent to open resection with respect to the oncological results and has short-term advantages in the early postoperative outcome. The aim of this study was to investigate whether laparoscopic colonic resection has become established as the standard in routine treatment. Data from the multicenter observational study "Quality assurance colonic cancer (primary tumor)" from the time period from 1 January 2009 to 21 December 2011 were evaluated with respect to the total proportion of laparoscopic colonic cancer resections and tumor localization and specifically for laparoscopic sigmoid colon cancer resections. A comparison between low and high volume clinics (< 30 versus ≥ 30 colonic cancer resections/year) was carried out. Laparoscopic colonic cancer resections were carried out in 12 % versus 21.4 % of low and high volume clinics, respectively (p < 0.001) with a significant increase for low volume clinics (from 8.0 % to 15.6 %, p < 0.001) and a constant proportion in high volume clinics (from 21.7 % to 21.1 %, p = 0.905). For sigmoid colon cancer laparoscopic resection was carried out in 49.7 % versus 47.6 % (p = 0.584). Differences were found between low volume and high volume clinics in the conversion rates (17.3 % versus 6.6 %, p < 0.001), the length of the resected portion (Ø 23.6 cm versus 36.0 cm, p < 0.001) and the lymph node yield (Ø n = 15.7 versus 18.2, p = 0.008). There were no differences between the two groups of clinics regarding postoperative morbidity and mortality. The postoperative morbidity and length of stay were significantly lower for laparoscopic sigmoid resection than for conventional sigmoid resection. The laparoscopic access route for colonic cancer resection is not the standard approach in the participating clinics. The laparoscopic access route has the highest proportion for sigmoid colon resection. The differences in the

  3. Combination of gefitinib and DNA methylation inhibitor decitabine exerts synergistic anti-cancer activity in colon cancer cells.

    Directory of Open Access Journals (Sweden)

    Yun-feng Lou

    Full Text Available Despite recent advances in the treatment of human colon cancer, the chemotherapy efficacy against colon cancer is still unsatisfactory. In the present study, effects of concomitant inhibition of the epidermal growth factor receptor (EGFR and DNA methyltransferase were examined in human colon cancer cells. We demonstrated that decitabine (a DNA methyltransferase inhibitor synergized with gefitinib (an EGFR inhibitor to reduce cell viability and colony formation in SW1116 and LOVO cells. However, the combination of the two compounds displayed minimal toxicity to NCM460 cells, a normal human colon mucosal epithelial cell line. The combination was also more effective at inhibiting the AKT/mTOR/S6 kinase pathway. In addition, the combination of decitabine with gefitinib markedly inhibited colon cancer cell migration. Furthermore, gefitinib synergistically enhanced decitabine-induced cytotoxicity was primarily due to apoptosis as shown by Annexin V labeling that was attenuated by z-VAD-fmk, a pan caspase inhibitor. Concomitantly, cell apoptosis resulting from the co-treatment of gefitinib and decitabine was accompanied by induction of BAX, cleaved caspase 3 and cleaved PARP, along with reduction of Bcl-2 compared to treatment with either drug alone. Interestingly, combined treatment with these two drugs increased the expression of XIAP-associated factor 1 (XAF1 which play an important role in cell apoptosis. Moreover, small interfering RNA (siRNA depletion of XAF1 significantly attenuated colon cancer cells apoptosis induced by the combination of the two drugs. Our findings suggested that gefitinib in combination with decitabine exerted enhanced cell apoptosis in colon cancer cells were involved in mitochondrial-mediated pathway and induction of XAF1 expression. In conclusion, based on the observations from our study, we suggested that the combined administration of these two drugs might be considered as a novel therapeutic regimen for treating colon

  4. Evaluation and SAR analysis of the cytotoxicity of tanshinones in colon cancer cells.

    Science.gov (United States)

    Wang, Lin; Liu, An; Zhang, Fei-Long; Yeung, John H K; Li, Xu-Qin; Cho, Chi-Hin

    2014-03-01

    This study was designed to evaluate the anti-cancer actions of tanshinone I and tanshinone IIA, and six derivatives of tanshinone IIA on normal and cancerous colon cells. Structure activity relationship (SAR) analysis was conducted to delineate the significance of the structural modifications of tanshinones for improved anti-cancer action. Tanshinone derivatives were designed and synthesized according to the literature. The cytotoxicity of different compounds on colon cancer cells was determined by the MTT assay. Apoptotic activity of the tanshinones was measured by flow cytometry (FCM). Tanshinone I and tanshinone IIA both exhibited significant cytotoxicity on colon cancer cells. They are more effective in p53(+/+) colon cancer cell line. It was also noted that the anti-cancer activity of tanshinone I was more potent and selective. Two of the derivatives of tanshinone IIA (N1 and N2) also exhibited cytotoxicity on colon cancer cells. The anti-colon cancer activity of tanshinone I was more potent and selective than tanshinone IIA, and is p53 dependent. The derivatives obtained by structural modifications of tanshinone IIA exhibited lower cytotoxicity on both normal and colon cancer cells. From steric and electronic characteristics point of view, it was concluded that structural modifications of ring A and furan or dihydrofuran ring D on the basic structure of tanshinones influences the activity. An increase of the delocalization of the A and B rings could enhance the cytotoxicity of such compounds, while a non-planar and small sized D ring region would provide improved anti-cancer activity. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  5. Neoadjuvant chemotherapy among patients treated for nonmetastatic breast cancer in a population with a high HIV prevalence in Johannesburg, South Africa.

    Science.gov (United States)

    Ruff, Paul; Cubasch, Herbert; Joffe, Maureen; Rosenbaum, Evan; Murugan, Nivashni; Tsai, Ming-Chih; Ayeni, Oluwatosin; Crew, Katherine D; Jacobson, Judith S; Neugut, Alfred I

    2018-01-01

    Neoadjuvant (primary) chemotherapy (NACT) is the standard of care for locally advanced breast cancer. It also allows for the short-term assessment of chemotherapy response; a pathological complete responses correspond to improved long-term breast cancer outcomes. In sub-Saharan Africa, many patients are diagnosed with large nonresectable tumors. We examined NACT use in breast cancer patients who visited public hospitals in Johannesburg, South Africa. We assessed demographic characteristics, tumor stage and grade, hormone receptor status, and human immunodeficiency virus (HIV) status of female patients diagnosed with nonmetastatic invasive carcinoma of the breast at Chris Hani Baragwanath Academic Hospital between January 1, 2009, and December 31, 2011. The patients received neoadjuvant, adjuvant, or no chemotherapy. Trastuzumab was unavailable. We developed logistic regression models to analyze the factors associated with NACT receipt in these patients. Of 554 women with nonmetastatic breast cancer, the median age at diagnosis was 52 years (range: 28-88 years). Only 5.8% of patients were diagnosed with stage I disease; 49.3% and 44.9% were diagnosed with stages II and III, respectively. Most patients had hormone-responsive tumors: luminal A, 38.1%; luminal B 1 (human epidermal growth factor receptor 2 [HER2]-negative and high grade), 12.5%, and luminal B 2 (HER2-positive any grade), 11.6%; 11.6% had a HER2-enriched tumor and 20.6% a triple-negative tumor. Eighty (14.4%) patients were HIV-positive. In total, 195 patients (35.2%) received NACT, 264 (47.7%) patients received adjuvant chemotherapy, and 95 patients (17.1%) received no chemotherapy, including 62 (11.2%) patients who received only hormonal therapy. Of patients receiving NACT, 125 (64.1%) were evaluable for clinical response. Eighty (64.0%) patients had a clinically significant response; 19 (15.2%) patients had a stable disease, and 26 (20.8%) patients had a progressive disease. Multivariate analysis

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

    Science.gov (United States)

    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.

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

    OpenAIRE

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

    2008-01-01

    Purpose Several multi-institutional prospective randomized trials have demonstrated short-term benefits using laparoscopy. Now the laparoscopic approach is accepted as an alternative to open surgery for colon cancer. However, in prior trials, the transverse colon was excluded. Therefore, it has not been determined whether laparoscopy can be used in the setting of transverse colon cancer. This study evaluated the peri-operative clinical outcomes and oncological quality by pathologic outcomes o...

  8. MINIMALLY INVASIVE APPROACH FOR RIGHT-SIDED COLON CANCER, COMPLICATED BY LARGE-BOWEL OBSTRUCTION

    Directory of Open Access Journals (Sweden)

    A. I. Chernookov

    2017-01-01

    Full Text Available The case demonstrates an opportunity of safe and successful colonic stenting to treat bowel obstruction with following laparoscopic radical intervention for right-sided colon cancer localization. The colonic stent as a “bridge to the surgery” improves immediate results and surviving rate in elderly patients with complicated right-sided colon cancer and severe concomitant disease.

  9. [Analysis of clinicopathologic and survival characteristics in patients with right-or left-sided colon cancer].

    Science.gov (United States)

    Hu, Junjie; Zhou, Zhixiang; Liang, Jianwei; Zhou, Haitao; Wang, Zheng; Zhang, Xingmao; Zeng, Weigen

    2015-07-28

    This study aimed to clarify the clinical and histological parameters, and survival difference between right- and left-sided colon cancer. We retrospectively analyzed the medical records (2006.1-2009.12) of 1 088 consecutive colon cancer patients who received surgery at our hospital. Right- and left-sided colon cancers were compared regarding the clinical and histological parameters. The survival analysis was performed by the Kaplan-Meier method, and the log-rank test was used to determine the statistical significance of differences. Right-sided colon cancer was associated with older age, a more advanced state, and poorly differentiated and undifferentiated adenocarcinoma (25.2% vs 13.2%), mucinous adenocarcinoma (33.5% vs 17.3%) and vascular invasion (9.9% vs 3.9%) were more commonly seen in right-sided colon cancer compared with right-sided colon cancer, and all these differences were statistically significant. Median overall survival was right, 67 months; and left, 68 months. The five-years overall survival of right- and left-sided colon cancer was I/II stage, 91.4% vs 88.6% (P = 0.819); III stage, 66.1% vs 75.4% (P = 0.010); and IV stage, 27.8% vs 38.5% (P = 0.020) respectively. Right- and left-sided colon cancers are significantly different regarding clinical and histological parameters. Right-sided colon cancers in stage III and IV have a worse prognosis.

  10. PPARδ deficiency disrupts hypoxia-mediated tumorigenic potential of colon cancer cells.

    Science.gov (United States)

    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 (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. © 2014 Wiley Periodicals, Inc.

  11. Colon cancer trends in Norway and Denmark by socio-economic group

    DEFF Research Database (Denmark)

    Lynge, Elsebeth; Martinsen, Jan Ivar; Larsen, Inger Kristin

    2015-01-01

    in incidence by socio-economic group. METHODS: Persons participating in the 1970 censuses in Norway and Denmark were aged 55-75 years in 1971-1980 (called pre-crossing period) and in 1991-2000 (called post-crossing period), respectively. Country, sex, age and socio-economic group-specific colon cancer......AIMS: Norway has experienced an unprecedented rapid and so far unexplained increase in colon cancer incidence. Norwegian rates passed Danish rates for men in 1985 and for women in 1990. This study aimed to unravel clues to the development in colon cancer incidence by investigating changes over time...... incidence rates. Percent change in the average rate from the pre- to the post-crossing period. RESULTS: In the pre-crossing period, Norwegian male managers/administrators had the highest colon cancer incidence, but the largest increase in incidence from the pre-to the post-crossing period was seen...

  12. The relation between lymph node status and survival in Stage I-III colon cancer

    DEFF Research Database (Denmark)

    Lykke, J.; Roikjær, Ole; Jess, P.

    2013-01-01

    Aim: This study involved a large nationwide Danish cohort to evaluate the hypothesis that a high lymph node harvest has a positive effect on survival in curative resected Stage I-III colon cancer and a low lymph node ratio has a positive effect on survival in Stage III colon cancer. Method......: Analysis of overall survival was conducted using a nationwide Danish cohort of patients treated with curative resection of Stage I-III colon cancer. All 8901 patients in Denmark diagnosed with adenocarcinoma of the colon and treated with curative resection in the period 2003-2008 were identified from...... independent prognostic factors in multivariate analysis. Conclusion: High lymph node count was associated with improved overall survival in colon cancer. Lymph node ratio was superior to N-stage in differentiating overall survival in Stage III colon cancer. Stage migration was observed....

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  14. Limitations of tissue micro array in Duke's B colon cancer

    DEFF Research Database (Denmark)

    Kjær-Frifeldt, Sanne; Lindebjerg, Jan; Brunner, Nils

    2012-01-01

    Tissue micro array (TMA) is widely used in cancer research in search of new predictive and prognostic markers. Colon cancer is known to be heterogeneous and the present study addresses some methodological aspects using cores of different size and analysing markers with different cellular distribu......Tissue micro array (TMA) is widely used in cancer research in search of new predictive and prognostic markers. Colon cancer is known to be heterogeneous and the present study addresses some methodological aspects using cores of different size and analysing markers with different cellular...

  15. Obesity-related colon cancer: dietary factors and their mechanisms of anticancer action.

    Science.gov (United States)

    Zeng, Huawei; Lazarova, Darina L

    2012-02-01

    Overweight/obesity is an epidemic in the US as well as in other developed countries, affecting two-thirds of Americans and an estimated 2.3 billion people worldwide. Obesity increases the risk for Type 2 diabetes, cardiovascular disease and cancer. For example, epidemiological studies have established a strong association between obesity and colon cancer. It is generally accepted that metabolic changes associated with overweight/obesity, particularly abdominal obesity and changes in adipocyte function, contribute to the increased risk of colon cancer. Understanding the mechanisms underlying this association is important for the development of preventive strategies for colon cancer. Part of these preventive strategies may be based on dietary factors, such as vitamins, minerals (e.g. selenium), fibre, phytochemicals and phenolic compounds. These anticancer nutrients may counteract the molecular changes associated with obesity. The present article reviews the evidence that inflammation and insulin resistance induced by obesity are the molecular mediators of the association between obesity and colon cancer. We also evaluate the evidence for the ability of dietary factors to target the obesity-induced changes and, thus, protect against colon cancer. © 2011 The Authors. Clinical and Experimental Pharmacology and Physiology © 2011 Blackwell Publishing Asia Pty Ltd.

  16. ER-Stress-Induced Differentiation Sensitizes Colon Cancer Stem Cells to Chemotherapy

    NARCIS (Netherlands)

    Wielenga, Mattheus C. B.; Colak, Selcuk; Heijmans, Jarom; van Lidth de Jeude, Jooske F.; Rodermond, Hans M.; Paton, James C.; Paton, Adrienne W.; Vermeulen, Louis; Medema, Jan Paul; van den Brink, Gijs R.

    2015-01-01

    Colon cancer stem cells (colon-CSCs) are more resistant to conventional chemotherapy than differentiated cancer cells. This subset of therapy refractory cells is therefore believed to play an important role in post-therapeutic tumor relapse. In order to improve the rate of sustained response to

  17. Role of microsatellite instability in colon cancer

    Directory of Open Access Journals (Sweden)

    M. Yu. Fedyanin

    2012-01-01

    Full Text Available Coloncancer is among leading causes of cancer morbidity and mortality both inRussiaand worldwide. Development of molecular biology lead to decoding of carcinogenesis and tumor progression mechanisms. These processes require accumulation of genetic and epigenetic alterations in a tumor cell.Coloncancer carcinogenesis is characterized by mutations cumulation in genes controlling growth and differentiation of epithelial cells, which leads to their genetic instability. Microsatellite instability is a type of genetic instability characterized by deterioration of mismatch DNA repair. This leads to faster accumulation of mutations in DNA. Loss of mismatch repair mechanism can easily be diagnosed by length of DNA microsatellites. These alterations are termed microsatellite instability. They can be found both in hereditary and sporadic colon cancers. This review covers the questions of microsatellite instability, its prognostic and predictive value in colon cancer.

  18. Explanation of colon cancer pathophysiology through analyzing the ...

    African Journals Online (AJOL)

    Abstract. Background: The colon plays a key role in regulating the homeostasis of bile acids. Aim: The present study aims to evaluate the influence of colon cancer towards the homeostasis of bile acids. Methods: The free and conjugated bile acids were determined using ultraperformance LC (UPLC) coupled with ABI 4000.

  19. Explanation of colon cancer pathophysiology through analyzing the ...

    African Journals Online (AJOL)

    Background: The colon plays a key role in regulating the homeostasis of bile acids. Aim: The present study aims to evaluate the influence of colon cancer towards the homeostasis of bile acids. Methods: The free and conjugated bile acids were determined using ultraperformance LC (UPLC) coupled with ABI 4000 QTRAP ...

  20. Variation in positron emission tomography use after colon cancer resection.

    Science.gov (United States)

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

    2015-05-01

    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. 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. 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. 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. Copyright © 2015 by American Society of Clinical Oncology.

  1. Laparoscopic versus open resection for transverse colon cancer.

    Science.gov (United States)

    Mistrangelo, Massimiliano; Allaix, Marco Ettore; Cassoni, Paola; Giraudo, Giuseppe; Arolfo, Simone; Morino, Mario

    2015-08-01

    Previous large randomized controlled trials comparing laparoscopic (LR) and open resection (OR) for colon cancer have not specifically analyzed the outcomes in patients with transverse colon cancer. The aims of this study were to evaluate the feasibility and safety of LR transverse colon cancer resection and to compare our findings with the results available in the literature. We performed a retrospective analysis of consecutive patients undergoing LR or OR for histologically proven adenocarcinoma of the transverse colon. A total of 123 patients were included in this study: 66 LR and 57 OR. Median operating time was similar in the two groups. Median blood loss was higher in the OR group, even though the difference was not statistically significant. The rate of conversion from LR to OR was 16.7 %. Return of bowel function occurred significantly earlier in the LR group. The incidence and severity of 30-day postoperative complications and mortality rates were similar in the two groups. The median hospital stay was significantly shorter in the LR group. There was a trend toward a greater number of lymph nodes harvested in the OR group than in the LR group, although the difference was not statistically significant. The time to first flatus and bowel movement was significantly earlier in the LR group. Five-year overall survival and disease-free survival rates were similar in the LR and OR groups (86.4 vs. 88.6 %, p = 0.770 and 80.4 vs. 77.3 %, p = 0.516, respectively). LR of transverse colon cancer is feasible and safe, with similar early short-term outcomes when compared to OR. Larger prospective comparative studies with long-term follow-up are needed to assess the oncological equivalence of the two approaches.

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

    DEFF Research Database (Denmark)

    Smith, Natalie R; Jensen, Britt W; Zimmermann, Esther

    2016-01-01

    BACKGROUND: Birth weight has inconsistent associations with colorectal cancer, possibly due to different anatomic features of the colon versus the rectum. The aim of this study was to investigate the association between birth weight and colon and rectal cancers separately. METHODS: 193,306 children....... No significant sex differences were observed; therefore combined results are presented. Birth weight was positively associated with colon cancers with a HR of 1.14 (95% CI, 1.04-1.26) per kilogram of birth weight. For rectal cancer a significant association was not observed for birth weights below 3.5kg. Above 3...

  3. PGE{sub 2}-induced colon cancer growth is mediated by mTORC1

    Energy Technology Data Exchange (ETDEWEB)

    Dufour, Marc, E-mail: Marc.dufour@chuv.ch; Faes, Seraina, E-mail: Seraina.faes@chuv.ch; Dormond-Meuwly, Anne, E-mail: Anne.meuwly-Dormond@chuv.ch; Demartines, Nicolas, E-mail: Demartines@chuv.ch; Dormond, Olivier, E-mail: Olivier.dormond@chuv.ch

    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.

  4. Spontaneous regression of transverse colon cancer: a case report.

    Science.gov (United States)

    Chida, Keigo; Nakanishi, Kazuaki; Shomura, Hiroki; Homma, Shigenori; Hattori, Atsuo; Kazui, Keizo; Taketomi, Akinobu

    2017-12-01

    Spontaneous regression (SR) of many malignant tumors has been well documented, with an approximate incidence of one per 60,000-100,000 cancer patients. However, SR of colorectal cancer (CRC) is very rare, accounting for less than 2% of such cases. We report a case of SR of transverse colon cancer in an 80-year-old man undergoing outpatient follow-up after surgical treatment of early gastric cancer. Colonoscopy (CS) revealed a Borrmann type II tumor in the transverse colon measuring 30 × 30 mm. Because the patient underwent anticoagulant therapy, we did not perform a biopsy at that time. A second CS was performed 1 week after the initial examination and revealed tumor shrinkage to a diameter of 20 mm and a shift to the Borrmann type III morphology. Biopsy revealed a poorly differentiated adenocarcinoma. One week after the second CS, we performed a partial resection of the transverse colon and D2 lymph node dissection. Histopathology revealed inflammatory cell infiltration and fibrosis from the submucosal to muscularis propria layers in the absence of cancer cells, leading to pathological staging of pStage 0 (T0N0). The patient had an uneventful recovery, and CS performed at 5 months postoperatively revealed the absence of a tumor in the colon and rectum. The patient continues to be followed up as an outpatient at 12 months postoperatively, and no recurrence has been observed.

  5. MAP kinase genes and colon and rectal cancer

    Science.gov (United States)

    Slattery, Martha L.

    2012-01-01

    Mitogen-activated protein kinase (MAPK) pathways regulate many cellular functions including cell proliferation, differentiation, migration and apoptosis. We evaluate genetic variation in the c-Jun-N-terminal kinases, p38, and extracellular regulated kinases 1/2 MAPK-signaling pathways and colon and rectal cancer risk using data from population-based case-control studies (colon: n = 1555 cases, 1956 controls; rectal: n = 754 cases, 959 controls). We assess 19 genes (DUSP1, DUSP2, DUSP4, DUSP6, DUSP7, MAP2K1, MAP3K1, MAP3K2, MAP3K3, MAP3K7, MAP3K9, MAP3K10, MAP3K11, MAPK1, MAPK3, MAPK8, MAPK12, MAPK14 and RAF1). MAP2K1 rs8039880 [odds ratio (OR) = 0.57, 95% confidence interval (CI) = 0.38, 0.83; GG versus AA genotype] and MAP3K9 rs11625206 (OR = 1.41, 95% CI = 1.14, 1.76; recessive model) were associated with colon cancer (P adj value rectal cancer (P adj cancer risk. Genetic variants had unique associations with KRAS, TP53 and CIMP+ tumors. DUSP2 rs1724120 [hazard rate ratio (HRR) = 0.72, 95%CI = 0.54, 0.96; AA versus GG/GA), MAP3K10 rs112956 (HRR = 1.40, 95% CI = 1.10, 1.76; CT/TT versus CC) and MAP3K11 (HRR = 1.76, 95% CI 1.18, 2.62 TT versus GG/GT) influenced survival after diagnosis with colon cancer; MAP2K1 rs8039880 (HRR = 2.53, 95% CI 1.34, 4.79 GG versus AG/GG) and Raf1 rs11923427 (HRR = 0.59 95% CI = 0.40, 0.86; AA versus TT/TA) were associated with rectal cancer survival. These data suggest that genetic variation in the MAPK-signaling pathway influences colorectal cancer risk and survival after diagnosis. Associations may be modified by lifestyle factors that influence inflammation and oxidative stress. PMID:23027623

  6. Efficacy of laser capture microdissection plus RT-PCR technique in analyzing gene expression levels in human gastric cancer and colon cancer

    International Nuclear Information System (INIS)

    Makino, Hiroshi; Uetake, Hiroyuki; Danenberg, Kathleen; Danenberg, Peter V; Sugihara, Kenichi

    2008-01-01

    Thymidylate synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase, and orotate phosphoribosyltransferase gene expressions are reported to be valid predictive markers for 5-fluorouracil sensitivity to gastrointestinal cancer. For more reliable predictability, their expressions in cancer cells and stromal cells in the cancerous tissue (cancerous stroma) have been separately investigated using laser capture microdissection. Thymidylate synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase, and orotate phosphoribosyltransferase mRNA in cancer cells and cancerous stroma from samples of 47 gastric and 43 colon cancers were separately quantified by reverse transcription polymerase chain reaction after laser capture microdissection. In both gastric and colon cancers, thymidylate synthase and orotate phosphoribosyltransferase mRNA expressions were higher (p < 0.0001, p <0.0001 respectively in gastric cancer and P = 0.0002, p < 0.0001 respectively in colon cancer) and dihydropyrimidine dehydrogenase mRNA expressions were lower in cancer cells than in cancerous stroma (P = 0.0136 in gastric cancer and p < 0.0001 in colon cancer). In contrast, thymidine phosphorylase mRNA was higher in cancer cells than in cancerous stroma in gastric cancer (p < 0.0001) and lower in cancer cells than in cancerous stroma in colon cancer (P = 0.0055). By using this method, we could estimate gene expressions separately in cancer cells and stromal cells from colon and gastric cancers, in spite of the amount of stromal tissue. Our method is thought to be useful for accurately evaluating intratumoral gene expressions

  7. Efficient and reproducible identification of mismatch repair deficient colon cancer

    DEFF Research Database (Denmark)

    Joost, Patrick; Bendahl, Pär-Ola; Halvarsson, Britta

    2013-01-01

    BACKGROUND: The identification of mismatch-repair (MMR) defective colon cancer is clinically relevant for diagnostic, prognostic and potentially also for treatment predictive purposes. Preselection of tumors for MMR analysis can be obtained with predictive models, which need to demonstrate ease...... of application and favorable reproducibility. METHODS: We validated the MMR index for the identification of prognostically favorable MMR deficient colon cancers and compared performance to 5 other prediction models. In total, 474 colon cancers diagnosed ≥ age 50 were evaluated with correlation between...... clinicopathologic variables and immunohistochemical MMR protein expression. RESULTS: Female sex, age ≥60 years, proximal tumor location, expanding growth pattern, lack of dirty necrosis, mucinous differentiation and presence of tumor-infiltrating lymphocytes significantly correlated with MMR deficiency. Presence...

  8. The Cambridge Prognostic Groups for improved prediction of disease mortality at diagnosis in primary non-metastatic prostate cancer: a validation study.

    Science.gov (United States)

    Gnanapragasam, V J; Bratt, O; Muir, K; Lee, L S; Huang, H H; Stattin, P; Lophatananon, A

    2018-02-28

    The purpose of this study is to validate a new five-tiered prognostic classification system to better discriminate cancer-specific mortality in men diagnosed with primary non-metastatic prostate cancer. We applied a recently described five-strata model, the Cambridge Prognostic Groups (CPGs 1-5), in two international cohorts and tested prognostic performance against the current standard three-strata classification of low-, intermediate- or high-risk disease. Diagnostic clinico-pathological data for men obtained from the Prostate Cancer data Base Sweden (PCBaSe) and the Singapore Health Study were used. The main outcome measure was prostate cancer mortality (PCM) stratified by age group and treatment modality. The PCBaSe cohort included 72,337 men, of whom 7162 died of prostate cancer. The CPG model successfully classified men with different risks of PCM with competing risk regression confirming significant intergroup distinction (p study of nearly 75,000 men confirms that the CPG five-tiered prognostic model has superior discrimination compared to the three-tiered model in predicting prostate cancer death across different age and treatment groups. Crucially, it identifies distinct sub-groups of men within the old intermediate-risk and high-risk criteria who have very different prognostic outcomes. We therefore propose adoption of the CPG model as a simple-to-use but more accurate prognostic stratification tool to help guide management for men with newly diagnosed prostate cancer.

  9. SOX9 Expression Predicts Relapse of Stage II Colon Cancer Patients

    DEFF Research Database (Denmark)

    Espersen, Maiken Lise Marcker; Linnemann, Dorte; Christensen, Ib Jarle

    2016-01-01

    The aim of this study was to investigate if the protein expression of Sex-determining region y-box 9 (SOX9) in primary tumors could predict relapse of stage II colon cancer patients.144 patients with stage II primary colon cancer were retrospectively enrolledin the study. SOX9 expression...

  10. Differential expression of carbohydrate antigen 19-9 in human colorectal cancer: A comparison with colon and rectal cancers

    Science.gov (United States)

    ZHANG, SHUAI; CHEN, YIJUN; ZHU, ZHANMENG; DING, YUNLONG; REN, SHUANGYI; ZUO, YUNFEI

    2013-01-01

    Colorectal cancer is one of the leading causes of cancer-related mortality, being the third most commonly diagnosed cancer among men and the second among women. Accumulating evidence regarding carbohydrate antigen (CA) demonstrated that tumor-associated antigens are clinically useful for the diagnosis, staging and monitoring of human gastrointestinal cancers, particularly colorectal cancer. There has been an extensive investigation for sensitive and specific markers of this disease. Currently, the gastrointestinal cancer-associated carbohydrate antigen 19-9 (CA19-9) is the most widely applied tumor marker in cancer diagnosis. Despite a similar etiology and cancer incidence rates, there are anatomical and clinical differences between colon and rectal cancer, as well as differences regarding tumor progression and adjuvant treatments. To investigate whether CA19-9 is differentially expressed between colon and rectal cancer, we conducted a differential analysis of serum CA19-9 levels among 227 cases of colorectal cancer, analyzing gender, age, Dukes’ stage and distant metastasis for human colon and rectal cancer as a single entity, separately and as matched pairs. We demonstrated that the serum CA19-9 levels in colorectal cancer were upregulated in advanced stages with distant metastasis. By contrast, the serum CA19-9 levels in colon cancer displayed a differential and upregulated behavior in advanced stages with distant metastasis. By analyzing as matched pairs, the upregulated serum CA19-9 levels in rectal cancer during the early stages without distant metastasis further supported our hypothesis that the expression of CA19-9 displays a site-specific differential behavior. The integrative analysis suggested a significant difference between human colon and rectal cancer, justifying individualized therapy for these two types of cancer. PMID:24649295

  11. Mlh1 deficiency in normal mouse colon mucosa associates with chromosomally unstable colon cancer

    Science.gov (United States)

    Pussila, Marjaana; Törönen, Petri; Einarsdottir, Elisabet; Katayama, Shintaro; Krjutškov, Kaarel; Holm, Liisa; Kere, Juha; Peltomäki, Päivi; Mäkinen, Markus J; Linden, Jere; Nyström, Minna

    2018-01-01

    Abstract Colorectal cancer (CRC) genome is unstable and different types of instabilities, such as chromosomal instability (CIN) and microsatellite instability (MSI) are thought to reflect distinct cancer initiating mechanisms. Although 85% of sporadic CRC reveal CIN, 15% reveal mismatch repair (MMR) malfunction and MSI, the hallmarks of Lynch syndrome with inherited heterozygous germline mutations in MMR genes. Our study was designed to comprehensively follow genome-wide expression changes and their implications during colon tumorigenesis. We conducted a long-term feeding experiment in the mouse to address expression changes arising in histologically normal colonic mucosa as putative cancer preceding events, and the effect of inherited predisposition (Mlh1+/−) and Western-style diet (WD) on those. During the 21-month experiment, carcinomas developed mainly in WD-fed mice and were evenly distributed between genotypes. Unexpectedly, the heterozygote (B6.129-Mlh1tm1Rak) mice did not show MSI in their CRCs. Instead, both wildtype and heterozygote CRC mice showed a distinct mRNA expression profile and shortage of several chromosomal segregation gene-specific transcripts (Mlh1, Bub1, Mis18a, Tpx2, Rad9a, Pms2, Cenpe, Ncapd3, Odf2 and Dclre1b) in their colon mucosa, as well as an increased mitotic activity and abundant numbers of unbalanced/atypical mitoses in tumours. Our genome-wide expression profiling experiment demonstrates that cancer preceding changes are already seen in histologically normal colon mucosa and that decreased expressions of Mlh1 and other chromosomal segregation genes may form a field-defect in mucosa, which trigger MMR-proficient, chromosomally unstable CRC. PMID:29701748

  12. Could JC virus provoke metastasis in colon cancer?

    Science.gov (United States)

    Sinagra, Emanuele; Raimondo, Dario; Gallo, Elena; Stella, Mario; Cottone, Mario; Orlando, Ambrogio; Rossi, Francesca; Orlando, Emanuele; Messina, Marco; Tomasello, Giovanni; Lo Monte, Attilio Ignazio; La Rocca, Ennio; Rizzo, Aroldo Gabriele

    2014-01-01

    AIM: To evaluate the prevalence of John Cunningham virus (JC virus) in a small cohort of patients with colon cancer and to assess its presence in hepatic metastasis. METHODS: Nineteen consecutive patients with histologically diagnosed colon cancer were included in our study, together with ten subjects affected by histologically and serologically diagnosed hepatitis C virus infection. In the patients included in the colon cancer group, JC virus was searched for in the surgical specimen; in the control group, JC virus was searched for in the hepatic biopsy. The difference in the prevalence of JC virus in the hepatic biopsy between the two groups was assessed through the χ2 test. RESULTS: Four out of 19 patients with colon cancer had a positive polymerase chain reaction (PCR) test for JC virus, and four had liver metastasis. Among the patients with liver metastasis, three out of four had a positive PCR test for JC virus in the surgical specimen and in the liver biopsy; the only patient with liver metastasis with a negative test for JC virus also presented a negative test for JC virus in the surgical specimen. In the control group of patients with hepatitis C infection, none of the ten patients presented JC virus infection in the hepatic biopsy. The difference between the two groups regarding JC virus infection was statistically significant (χ2 = 9.55, P = 0.002). CONCLUSION: JC virus may play a broader role than previously thought, and may be mechanistically involved in the late stages of these tumors. PMID:25400458

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

    Science.gov (United States)

    2018-02-22

    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

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

    Science.gov (United States)

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

    1997-01-01

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

  15. Stage dependent expression and tumor suppressive function of FAM134B (JK1) in colon cancer.

    Science.gov (United States)

    Islam, Farhadul; Gopalan, Vinod; Wahab, Riajul; Smith, Robert A; Qiao, Bin; Lam, Alfred King-Yin

    2017-01-01

    The aims of the present study are to investigate sub-cellular location, differential expression in different cancer stages and functional role of FAM134B in colon cancer development. FAM134B expression was studied and quantified at protein and mRNA levels in cell lines using immunocytochemistry, Western blot and real-time PCR. In vitro functional assays and an in vivo xenotransplantation mouse models were used to investigate the molecular role of FAM134B in cancer cell biology in response to FAM134B silencing with shRNA lentiviral particles. FAM134B protein was noted in both cytoplasm and nuclei of cancer cells. In cancer cells derived from stage IV colon cancer, FAM134B expression was remarkably reduced when compared to non-cancer colon cells and cancer cells derived from stage II colon cancer. FAM134B knockdown significantly (P colon cancer cells following lentiviral transfection. Furthermore, FAM134B suppression significantly increased (34-52%; P cancer suppressor gene in colon cancer. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. MicroRNA-98 Suppress Warburg Effect by Targeting HK2 in Colon Cancer Cells.

    Science.gov (United States)

    Zhu, Weimin; Huang, Yijiao; Pan, Qi; Xiang, Pei; Xie, Nanlan; Yu, Hao

    2017-03-01

    Warburg effect is a hallmark of cancer cells. Accumulating evidence suggests that microRNAs (miRs) could regulate such metabolic reprograming. Aberrant expression of miR-98 has been observed in many types of cancers. However, its functions and significance in colon cancer remain largely elusive. To investigate miR-98 expression and the biological functions in colon cancer progression. miR-98 expression levels were determined by quantitative RT-PCR in 215 cases of colon cancer samples. miR-98 mimic or inhibitor was used to test the biological functions in SW480 and HCT116 cells, followed by cell proliferation assay, lactate production, glucose uptake, and cellular ATP levels assay and extracellular acidification rates measurement. Western blot and luciferase assay were used to identify the target of miR-98. miR-98 was significantly down-regulated in colon cancer tissues compared to adjacent colon tissues and acted as a suppressor for Warburg effect in cancer cells. miR-98 inhibited glycolysis by directly targeting hexokinase 2, or HK2, illustrating a novel pathway to mediate Warburg effect of cancer cells. In vitro experiments further indicated that HK2 was involved in miR-98-mediated suppression of glucose uptake, lactate production, and cell proliferation. In addition, we detected HK2 expression in colon cancer tissues and found that the expressions of miR-98 and HK2 were negatively correlated. miR-98 acts as tumor suppressor gene and inhibits Warburg effect in colon cancer cells, which provided potential targets for clinical treatments.

  17. Incisional hernias after open versus laparoscopic surgery for colonic cancer

    DEFF Research Database (Denmark)

    Jensen, Kristian K.; Krarup, Peter-Martin; Scheike, Thomas

    2016-01-01

    patients operated on electively for colonic cancer with primary anastomosis in Denmark from 2001 to 2008. Patient data were obtained from the database of the Danish Colorectal Cancer Group and merged with data from the National Patient Registry. Multivariable Cox regression and competing risks analysis......, fascial dehiscence, anastomotic leak, and body mass index >25 kg/m(2). CONCLUSIONS: This nationwide analysis demonstrated that laparoscopic as compared with open access for curative resection of colonic cancer was associated with a decreased risk of incisional hernia formation....

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

    Science.gov (United States)

    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.

  19. Redefining Adjuvant Therapy for Colon Cancer

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  1. Colon cancer and content of nitrates and magnesium in drinking water.

    Science.gov (United States)

    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.

  2. Invasive ductal breast cancer metastatic to the sigmoid colon

    Directory of Open Access Journals (Sweden)

    Zhou Xiao-cong

    2012-11-01

    Full Text Available Abstract The most common sites of breast cancer metastasis are the bone, lung, liver and brain. However, colonic metastases from breast cancer are very rare in the clinic. We describe an unusual case of sigmoid colonic metastasis from invasive ductal breast cancer. With this report, we should increase the clinical awareness that any patient with a colorectal lesion and a history of malignancy should be considered to have a metastasis until proven otherwise. Early diagnosis is very important, which enables prompt initiation of systemic treatment, such as chemotherapy, endocrine therapy or both, thus avoiding unnecessary radical surgical resection and improving the prognosis.

  3. FIRST-LINE TREATMENT IN PATIENTS WITH INOPERABLE METASTATIC COLON CANCER

    Directory of Open Access Journals (Sweden)

    M. Yu. Fedyanin

    2014-01-01

    Full Text Available First-line therapy for metastatic colon cancer is most important for a patient. Its median time to progression constitutes the bulk of the patient’s survival. Clearly, it is necessary to choose the most effective combinations of targeted drugs and chemotherapy regimens. The choice of therapy for patients with colon cancer is governed by both the clinical characteristics of the disease and the molecular changes of a tumor. In recent literature, there has been a great deal of evidence for the use of targeted drugs in different clinical situations; the results of comparative trials of different treatment combinations have been published. This all determines the reconsideration of the choice of a treatment regimen in patients with metastatic colon cancer; it is the topic of the present review.

  4. MicroRNA-215 suppresses cell proliferation, migration and invasion of colon cancer by repressing Yin-Yang 1

    International Nuclear Information System (INIS)

    Chen, Zehong; Han, Siqi; Huang, Wensheng; Wu, Jialin; Liu, Yuyi; Cai, Shirong; He, Yulong; Wu, Suijing; Song, Wu

    2016-01-01

    Colorectal cancer is one of the most common malignant tumors worldwide with rising incidence. MicroRNAs are small non-coding RNAs that implicate in multiple physiological or pathological processes. The aberrant expression of miRNA-215 (miR-215) has been illustrated in various types of cancers. However, the expression of miR-215 in human colon cancer and the biological roles of it remain largely unknown. We conducted this study to explore the expression and the function of miR-215 in human colon cancer. The results showed that miR-215 was remarkably downregulated in colon cancer tissues and cell lines. Overexpression of miR-215 by miR-215 mimic significantly inhibited colon cancer cell proliferation, migration and invasion while knockdown of miR-215 by miR-215 inhibitor exerted reverse effects. Furthermore, we newly identified Yin-Yang 1(YY1) as a direct target of miR-215 which could rescue the effects of miR-215 on colon cancer cells. In summary, our investigation revealed that miR-215 was downregulated in colon cancer and it suppressed colon cancer cell proliferation, migration and invasion by directly targeting YY1. - Highlights: • MiR-215 expression was decreased in colon cancer tissues and cell lines. • Mir-215 inhibited colon cancer cell proliferation, migration and invasion. • MiR-215 targeted YY1 directly. • The effects of miR-215 on colon cancer cells were mediated by YY1.

  5. The impact of incisional hernia on mortality after colonic cancer resection

    DEFF Research Database (Denmark)

    Jensen, Kristian Kiim; Erichsen, Rune; Krarup, Peter Martin

    2016-01-01

    intended colonic resection for cancer with primary anastomosis between 2001 and 2008 were included. The exposure of interest was incisional hernia, as registered in the NPR, and the outcome was long-term overall mortality. Extended cox regression analysis was used to adjust for confounding variables...... the impact of incisional hernia on mortality after colonic cancer resection. METHOD: This was a nationwide cohort study comprising data from the Danish Colorectal Cancer Group's database, the Danish National Patient Registry (NPR), and the Danish Central Person Registry. Patients who underwent curatively...... with increased mortality (adjusted hazard ratio 2.35, 95 % confidence interval 1.39-3.98), while incisional hernia repair did not increase mortality (adjusted hazard ratio 0.81, 95 % confidence interval 0.68-0.97). CONCLUSIONS: Incisional hernia diagnosis or repair subsequent to colonic cancer resection did...

  6. Procaine Induces Epigenetic Changes in HCT116 Colon Cancer Cells

    Directory of Open Access Journals (Sweden)

    Hussein Sabit

    2016-01-01

    Full Text Available 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.

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

    Science.gov (United States)

    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

  8. Breast Cancer Cell Colonization of the Human Bone Marrow Adipose Tissue Niche.

    Science.gov (United States)

    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

    2015-12-01

    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. 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. 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. 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. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  9. MicroRNA-320a suppresses human colon cancer cell proliferation by directly targeting β-catenin

    International Nuclear Information System (INIS)

    Sun, Jian-Yong; Huang, Yi; Li, Ji-Peng; Zhang, Xiang; Wang, Lei; Meng, Yan-Ling; Yan, Bo; Bian, Yong-Qian; Zhao, Jing; Wang, Wei-Zhong

    2012-01-01

    Highlights: ► miR-320a is downregulated in human colorectal carcinoma. ► Overexpression of miR-320a inhibits colon cancer cell proliferation. ► β-Catenin is a direct target of miR-320a in colon cancer cells. ► miR-320a expression inversely correlates with mRNA expression of β-catenin’s target genes in human colon carcinoma. -- Abstract: Recent profile studies of microRNA (miRNA) expression have documented a deregulation of miRNA (miR-320a) in human colorectal carcinoma. However, its expression pattern and underlying mechanisms in the development and progression of colorectal carcinoma has not been elucidated clearly. Here, we performed real-time PCR to examine the expression levels of miR-320a in colon cancer cell lines and tumor tissues. And then, we investigated its biological functions in colon cancer cells by a gain of functional strategy. Further more, by the combinational approaches of bioinformatics and experimental validation, we confirmed target associations of miR-320a in colorectal carcinoma. Our results showed that miR-320a was frequently downregulated in cancer cell lines and colon cancer tissues. And we demonstrated that miR-320a restoration inhibited colon cancer cell proliferation and β-catenin, a functionally oncogenic molecule was a direct target gene of miR-320a. Finally, the data of real-time PCR showed the reciprocal relationship between miR-320a and β-catenin’s downstream genes in colon cancer tissues. These findings indicate that miR-320a suppresses the growth of colon cancer cells by directly targeting β-catenin, suggesting its application in prognosis prediction and cancer treatment.

  10. MicroRNA-320a suppresses human colon cancer cell proliferation by directly targeting {beta}-catenin

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Jian-Yong [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 710032 Xi' an (China); Huang, Yi [Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, 710032 Xi' an (China); Li, Ji-Peng [State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 710032 Xi' an (China); Zhang, Xiang; Wang, Lei [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); Meng, Yan-Ling [Department of Immunology, Fourth Military Medical University, 710032 Xi' an (China); Yan, Bo [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); Bian, Yong-Qian [State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 710032 Xi' an (China); Zhao, Jing [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); Wang, Wei-Zhong, E-mail: weichang@fmmu.edu.cn [State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 710032 Xi' an (China); and others

    2012-04-20

    Highlights: Black-Right-Pointing-Pointer miR-320a is downregulated in human colorectal carcinoma. Black-Right-Pointing-Pointer Overexpression of miR-320a inhibits colon cancer cell proliferation. Black-Right-Pointing-Pointer {beta}-Catenin is a direct target of miR-320a in colon cancer cells. Black-Right-Pointing-Pointer miR-320a expression inversely correlates with mRNA expression of {beta}-catenin's target genes in human colon carcinoma. -- Abstract: Recent profile studies of microRNA (miRNA) expression have documented a deregulation of miRNA (miR-320a) in human colorectal carcinoma. However, its expression pattern and underlying mechanisms in the development and progression of colorectal carcinoma has not been elucidated clearly. Here, we performed real-time PCR to examine the expression levels of miR-320a in colon cancer cell lines and tumor tissues. And then, we investigated its biological functions in colon cancer cells by a gain of functional strategy. Further more, by the combinational approaches of bioinformatics and experimental validation, we confirmed target associations of miR-320a in colorectal carcinoma. Our results showed that miR-320a was frequently downregulated in cancer cell lines and colon cancer tissues. And we demonstrated that miR-320a restoration inhibited colon cancer cell proliferation and {beta}-catenin, a functionally oncogenic molecule was a direct target gene of miR-320a. Finally, the data of real-time PCR showed the reciprocal relationship between miR-320a and {beta}-catenin's downstream genes in colon cancer tissues. These findings indicate that miR-320a suppresses the growth of colon cancer cells by directly targeting {beta}-catenin, suggesting its application in prognosis prediction and cancer treatment.

  11. Time- and dose-dependent effects of curcumin on gene expression in human colon cancer cells

    NARCIS (Netherlands)

    Erk, M.J. van; Teuling, E.; Staal, Y.C.M.; Huybers, S.; Bladeren, P.J. van; Aarts, J.M.M.J.G.; Ommen, B. van

    2004-01-01

    Background. Curcumin is a spice and a coloring food compound with a promising role in colon cancer prevention. Curcumin protects against development of colon tumors in rats treated with a colon carcinogen, in colon cancer cells curcumin can inhibit cell proliferation and induce apoptosis, it is an

  12. Time- and dose-dependent effects of curcumin on gene expression in human colon cancer cells

    NARCIS (Netherlands)

    Erk, van M.J.; Teuling, E.; Staal, Y.C.M.; Huybers, S.; Bladeren, van P.J.; Aarts, J.M.M.J.G.; Ommen, van B.

    2004-01-01

    Background: Curcumin is a spice and a coloring food compound with a promising role in colon cancer prevention. Curcumin protects against development of colon tumors in rats treated with a colon carcinogen, in colon cancer cells curcumin can inhibit cell proliferation and induce apoptosis, it is an

  13. Time- and dose-dependent effects of curcumin on gene expression in human colon cancer cells

    NARCIS (Netherlands)

    Van Erk, Marjan J; Teuling, Eva; Staal, Yvonne C. M.; Huybers, Sylvie; Van Bladeren, Peter J; Aarts, Jac MMJG; Van Ommen, Ben

    2004-01-01

    BACKGROUND: Curcumin is a spice and a coloring food compound with a promising role in colon cancer prevention. Curcumin protects against development of colon tumors in rats treated with a colon carcinogen, in colon cancer cells curcumin can inhibit cell proliferation and induce apoptosis, it is an

  14. Micronutrient intake and risk of colon and rectal cancer in a Danish cohort.

    Science.gov (United States)

    Roswall, Nina; Olsen, Anja; Christensen, Jane; Dragsted, Lars O; Overvad, Kim; Tjønneland, Anne

    2010-02-01

    Micronutrients may protect against colorectal cancer. Especially folate has been considered potentially preventive. However, studies on folate and colorectal cancer have found contradicting results; dietary folate seems preventive, whereas folic acid in supplements and fortification may increase the risk. To evaluate the association between intake of vitamins C, E, folate and beta-carotene and colorectal cancer risk, focusing on possibly different effects of dietary, supplemental and total intake, and on potential effect modification by lifestyle factors. In a prospective cohort study of 56,332 participants aged 50-64 years, information on diet, supplements and lifestyle was collected through questionnaires. 465 Colon and 283 rectal cancer cases were identified during follow-up. Incidence rate ratios of colon and rectal cancers related to micronutrient intake were calculated using Cox proportional hazard analyses. The present study found a protective effect of dietary but not supplemental folate on colon cancer. No association with any other micronutrient was found. Rectal cancer did not seem associated with any micronutrient. For both colon and rectal cancer, we found an interaction between dietary folate and alcohol intake, with a significant, preventive effect among those consuming above 10g alcohol/day only. This study adds further weight to the evidence that dietary folate protects against colon cancer, and specifies that there is a source-specific effect, with no preventive effect of supplemental folic acid. Further studies should thus take source into account. Vitamins C, E and beta-carotene showed no relation with colorectal cancer.

  15. Descriptive characteristics of colon and rectal cancer recurrence in a Danish population-based study.

    Science.gov (United States)

    Holmes, Ashley C; Riis, Anders H; Erichsen, Rune; Fedirko, Veronika; Ostenfeld, Eva Bjerre; Vyberg, Mogens; Thorlacius-Ussing, Ole; Lash, Timothy L

    2017-08-01

    Recurrence is a common outcome among patients that have undergone an intended curative resection for colorectal cancer. However, data on factors that influence colorectal cancer recurrence are sparse. We report descriptive characteristics of both colon and rectal cancer recurrence in an unselected population. We identified 21,152 patients with colorectal cancer diagnosed between May 2001 and December 2011 and registered with the Danish Colorectal Cancer Group. Recurrences were identified in 3198 colon and 1838 rectal cancer patients during follow-up. We calculated the frequency, proportion, and incidence rates of colon and rectal cancer recurrence within descriptive categories, and the cumulative five- and ten-year incidences of recurrence, treating death as a competing risk. We used a Cox proportional hazard model to calculate hazard ratios (HR) and 95% confidence intervals (CI). Recurrence risk was highest in the first three years of follow-up. Patients colon: 7.2 per 100 person-years; 95% CI: 6.5-7.9; rectum: 8.1 per 100 person-years; 95% CI: 7.2-9.0) and patients diagnosed with stage III cancer (colon HR: 5.70; 95% CI: 4.61-7.06; rectal HR: 7.02; 95% CI: 5.58-8.82) had increased risk of recurrence. Patients diagnosed with stage III cancer from 2009 to 2011 had a lower incidence of recurrence than those diagnosed with stage III cancer in the years before. Cumulative incidences of colon and rectal cancer recurrence were similar for both cancer types among each descriptive category. In this population, increases in colorectal cancer recurrence risk were associated with younger age and increasing stage at diagnosis. Cumulative incidence of recurrence did not differ by cancer type. Descriptive characteristics of colon and rectal cancer recurrence may help to inform patient-physician decision-making, and could be used to determine adjuvant therapies or tailor surveillance strategies so that recurrence may be identified early, particularly within the first 3 years of

  16. Survival of patients with colon and rectal cancer in central and northern Denmark, 1998-2009.

    Science.gov (United States)

    Ostenfeld, Eva B; Erichsen, Rune; Iversen, Lene H; Gandrup, Per; Nørgaard, Mette; Jacobsen, Jacob

    2011-01-01

    The prognosis for colon and rectal cancer has improved in Denmark over the past decades but is still poor compared with that in our neighboring countries. We conducted this population-based study to monitor recent trends in colon and rectal cancer survival in the central and northern regions of Denmark. Using the Danish National Registry of Patients, we identified 9412 patients with an incident diagnosis of colon cancer and 5685 patients diagnosed with rectal cancer between 1998 and 2009. We determined survival, and used Cox proportional hazard regression analysis to compare mortality over time, adjusting for age and gender. Among surgically treated patients, we computed 30-day mortality and corresponding mortality rate ratios (MRRs). The annual numbers of colon and rectal cancer increased from 1998 through 2009. For colon cancer, 1-year survival improved from 65% to 70%, and 5-year survival improved from 37% to 43%. For rectal cancer, 1-year survival improved from 73% to 78%, and 5-year survival improved from 39% to 47%. Men aged 80+ showed most pronounced improvements. The 1- and 5-year adjusted MRRs decreased: for colon cancer 0.83 (95% confidence interval CI: 0.76-0.92) and 0.84 (95% CI: 0.78-0.90) respectively; for rectal cancer 0.79 (95% CI: 0.68-0.91) and 0.81 (95% CI: 0.73-0.89) respectively. The 30-day postoperative mortality after resection also declined over the study period. Compared with 1998-2000 the 30-day MRRs in 2007-2009 were 0.68 (95% CI: 0.53-0.87) for colon cancer and 0.59 (95% CI: 0.37-0.96) for rectal cancer. The survival after colon and rectal cancer has improved in central and northern Denmark during the 1998-2009 period, as well as the 30-day postoperative mortality.

  17. Protective, elective lung irradiation in non-metastatic Ewing's sarcoma.

    Science.gov (United States)

    Marinova, L; Hristozova, I; Mihaylova, I; Perenovska, P

    2015-07-01

    Ewing's sarcoma in childhood is a disease from family of the peripheral primitive neuroectodermal tumours. For a period of 16 y (1984-2000), 34 children with Ewing's sarcoma were treated and followed in our department. Twenty-seven of these patients were without distant metastases. Complex treatment was applied to all these patients-chemotherapy VACA (vincristine, actinomycin D, cyclophosphamide, adriamycin), local radiotherapy to a total dose of 50-56 Gy +/- surgery. After, a local tumour control was achieved in 11 children with non-metastatic Ewing's sarcoma, elective whole lung irradiation to a total dose of 12-15 Gy was applied. Our experience in these 11 patients with non-metastatic Ewing's sarcoma, in whom elective lung irradiation was applied, showed significant reduction in the lung metastases, improved free of disease survival and overall survival. The achieved good treatment results necessitate extending this treatment approach through defining the risk groups of patients, suitable for elective lung radiotherapy combined with chemotherapy in non-metastatic Ewing's sarcoma. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Effectiveness of a multimedia-based educational intervention for improving colon cancer literacy in screening colonoscopy patients.

    Science.gov (United States)

    Hassinger, James P; Holubar, Stefan D; Pendlimari, Rajesh; Dozois, Eric J; Larson, David W; Cima, Robert R

    2010-09-01

    Limited data exist regarding colon cancer literacy in screening colonoscopy patients. We aimed to prospectively assess baseline colon cancer literacy and to determine whether a multimedia educational intervention was associated with improved colon cancer literacy. Colon cancer literacy was assessed in a convenience sample of colonoscopy patients before and after educational intervention. Statistically significant associations with colon cancer literacy scores were assessed by use of multivariate logistic regression analysis. Results are frequency (proportion), mean +/- SD, and odds ratio (OR (95% CI)). Seventy-three subjects participated: mean age, 57 +/- 12 years, 35 (48%) were women, 41 (57%) had a college degree, 43 (59%) had prior colonoscopy, 21 (29%) were accompanying family, and 16 (22%) were health care employees. Multivariate factors associated with a higher baseline colon cancer literacy score included health care employee status (7.9 (95% CI, 1.6-63); P = .02) and family colon cancer history (5.3 (95% CI, 1.3-25); P = .02). After multimedia education, mean scores improved from 53% +/- 23% to 88% +/- 12% (Delta = 35%; P screening colonoscopy. Multimedia-based educational intervention was an effective, satisfying strategy for addressing cancer-specific knowledge deficit in laypersons.

  19. Forward-viewing radial-array echoendoscope for staging of colon cancer beyond the rectum.

    Science.gov (United States)

    Kongkam, Pradermchai; Linlawan, Sittikorn; Aniwan, Satimai; Lakananurak, Narisorn; Khemnark, Suparat; Sahakitrungruang, Chucheep; Pattanaarun, Jirawat; Khomvilai, Supakij; Wisedopas, Naruemon; Ridtitid, Wiriyaporn; Bhutani, Manoop S; Kullavanijaya, Pinit; Rerknimitr, Rungsun

    2014-03-14

    To evaluate feasibility of the novel forward-viewing radial-array echoendoscope for staging of colon cancer beyond rectum as the first series. A retrospective study with prospectively entered database. From March 2012 to February 2013, a total of 21 patients (11 men) (mean age 64.2 years) with colon cancer beyond the rectum were recruited. The novel forward-viewing radial-array echoendoscope was used for ultrasonographic staging of colon cancer beyond rectum. Ultrasonographic T and N staging were recorded when surgical pathology was used as a gold standard. The mean time to reach the lesion and the mean time to complete the procedure were 3.5 and 7.1 min, respectively. The echoendoscope passed through the lesions in 13 patients (61.9%) and reached the cecum in 10 of 13 patients (76.9%). No adverse events were found. The lesions were located in the cecum (n = 2), ascending colon (n = 1), transverse colon (n = 2), descending colon (n = 2), and sigmoid colon (n = 14). The accuracy rate for T1 (n = 3), T2 (n = 4), T3 (n = 13) and T4 (n = 1) were 100%, 60.0%, 84.6% and 100%, respectively. The overall accuracy rates for the T and N staging of colon cancer were 81.0% and 52.4%, respectively. The accuracy rates among traversable lesions (n = 13) and obstructive lesions (n = 8) were 61.5% and 100%, respectively. Endoscopic ultrasound and computed tomography had overall accuracy rates of 81.0% and 68.4%, respectively. The echoendoscope is a feasible staging tool for colon cancer beyond rectum. However, accuracy of the echoendoscope needs to be verified by larger systematic studies.

  20. Radioimmunotoxin Therapy of Experimental Colon and Ovarian Cancer

    Energy Technology Data Exchange (ETDEWEB)

    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

  1. Radioimmunotoxin Therapy of Experimental Colon and Ovarian Cancer

    International Nuclear Information System (INIS)

    Buchsbaum, Donald J.; Vallera, Daniel A.

    2006-01-01

    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

  2. Risk factors for anastomotic dehiscence in colon cancer surgery

    DEFF Research Database (Denmark)

    Gessler, Bodil; Bock, David; Pommergaard, Hans-Christian

    2016-01-01

    PURPOSE: The aim of this was to assess potential risk factors for anastomotic dehiscence in colon cancer surgery in a national cohort. METHODS: All patients, who had undergone a resection of a large bowel segment with an anastomosis between 2008 and 2011, were identified in the Swedish Colon Cancer...... Registry. Patient factors, socioeconomic factors, surgical factors, and medication and hospital data were combined to evaluate risk factors for anastomotic dehiscence. RESULTS: The prevalence of anastomotic dehiscence was 4.3 % (497/11 565). Male sex, ASA classification III-IV, prescribed medications...

  3. A link between lipid metabolism and epithelial-mesenchymal transition provides a target for colon cancer therapy

    DEFF Research Database (Denmark)

    Sánchez-Martínez, Ruth; Cruz-Gil, Silvia; Gómez de Cedrón, Marta

    2015-01-01

    an epithelial-mesenchymal transition (EMT) program that promotes migration and invasion of colon cancer cells. The mesenchymal phenotype produced upon overexpression of these enzymes is reverted through reactivation of AMPK signaling. Furthermore, this network expression correlates with poorer clinical outcome...... of stage-II colon cancer patients. Finally, combined treatment with chemical inhibitors of ACSL/SCD selectively decreases cancer cell viability without reducing normal cells viability. Thus, ACSL/SCD network stimulates colon cancer progression through conferring increased energetic capacity and invasive...... and migratory properties to cancer cells, and might represent a new therapeutic opportunity for colon cancer treatment....

  4. Different matrix micro-environments in colon cancer and diverticular disease.

    Science.gov (United States)

    Klinge, U; Rosch, R; Junge, K; Krones, C J; Stumpf, M; Lynen-Jansen, P; Mertens, P R; Schumpelick, V

    2007-05-01

    The extracellular matrix and the interactive signalling between its components are thought to play a pivotal role for tumour development and metastasis formation. An altered matrix composition as potential underlying pathology for the development of colorectal cancer was hypothesized. In a retrospective study of patients with colon cancer, the extracellular matrix in tumour-free bowel specimen was investigated in comparison with non-infected bowel specimen from patients operated on for colonic diverticulosis. The following matrix parameters with known associations to tumour formation, cell proliferation, invasion and metastasis were analysed by immunohistochemistry and quantified by a scoring system: VEGF, TGF-beta, ESDN, CD117, c-erb-2, cyclin D1, p53, p27, COX-2, YB-1, collagen I/III, MMP-13, PAI and uPAR. Expression profiles and correlations were calculated. The comparison of the two groups revealed a significantly decreased immunostaining for CD117 and TGF-beta in the cancer group (8.5+/-2.6 vs 10.3+/-2,1 and 4.9+/-1.5 vs 8.1+/-3, respectively), whereas PAI scores were significantly higher than in patients with diverticular disease (8.1+/-1.6 vs 6.2+/-0.9). Overall correlation patterns of matrix parameters indicated pronounced differences between tumour-free tissue in cancer patients compared with patients with diverticular disease. Our results indicate distinct differences in the colonic tissue architecture between cancer patients and patients with diverticulitis that support the notion of an altered matrix composition predisposing to the development of colon cancer.

  5. DPEP1, expressed in the early stages of colon carcinogenesis, affects cancer cell invasiveness.

    Science.gov (United States)

    Toiyama, Yuji; Inoue, Yasuhiro; Yasuda, Hiromi; Saigusa, Susumu; Yokoe, Takeshi; Okugawa, Yoshinaga; Tanaka, Koji; Miki, Chikao; Kusunoki, Masato

    2011-02-01

    We investigated changes in the gene expression profile in colon cancer in order to identify gene markers that may be useful in the management of this disease. The Cancer Genome Anatomy Project was used to detect differences in gene expression between normal and cancer tissue. The overexpression of dipeptidase-1 (DPEP1) in cancer tissue was confirmed in a sample of 76 patients by real-time PCR. To identify the function of DPEP1, RNA interference (RNAi) was used to inactivate this gene in the colon cancer cell line. Immunohistochemical analysis was performed to characterize the pattern of DPEP1 expression in colon cancer. DPEP1 expression in cancer was significantly higher than that in normal tissue. However, DPEP1 expression decreased with pathological differentiation, lymph-node and distant metastasis. Patients with tumors with decreased DPEP1 expression showed a poorer prognosis, and this was also true of patients with tumors who are treated with curative intent. RNAi-mediated DPEP1 reduction in the colon cancer cell line did not result in cell proliferation or apoptosis, but was associated with an increased invasive ability. DPEP1 protein was observed on the apical side of the cancer cells, and is expressed in the early stages of carcinogenesis, even in adenomas of both sporadic colorectal cancer and familial adenomatous polyposis patients. DPEP1 expression in normal colonic mucosa is very low, but it is highly expressed in colorectal adenoma and cancer specimens and is negatively correlated with parameters of pathological aggressiveness and poor prognosis. DPEP1 is expressed in the early stages of colon carcinogenesis and affects cancer cell invasiveness.

  6. Cause-specific mortality in Scottish patients with colorectal cancer with and without type 2 diabetes (2000-2007).

    Science.gov (United States)

    Walker, J J; Brewster, D H; Colhoun, H M; Fischbacher, C M; Lindsay, R S; Wild, S H

    2013-07-01

    The objective of this study was to use Scottish national data to assess the influence of type 2 diabetes on (1) survival (overall and cause-specific) in multiple time intervals after diagnosis of colorectal cancer and (2) cause of death. Data from the Scottish Cancer Registry were linked to data from a population-based national diabetes register. All people in Scotland diagnosed with non-metastatic cancer of the colon or rectum in 2000-2007 were included. The effect of pre-existing type 2 diabetes on survival over four discrete time intervals (5 years) after cancer diagnosis was assessed by Cox regression. Cumulative incidence functions were calculated representing the respective probabilities of death from the competing causes of colorectal cancer, cardiovascular disease, other cancers and any other cause. Data were available for 19,505 people with colon or rectal cancer (1,957 with pre-existing diabetes). Cause-specific mortality analyses identified a stronger association between diabetes and cardiovascular disease mortality than that between diabetes and cancer mortality. Beyond 5 years after colon cancer diagnosis, diabetes was associated with a detrimental effect on all-cause mortality after adjustment for age, socioeconomic status and cancer stage (HR [95% CI]: 1.57 [1.19, 2.06] in men; 1.84 [1.36, 2.50] in women). For patients with rectal cancer, diabetes was not associated with differential survival in any time interval. Poorer survival observed for colon cancer associated with type 2 diabetes in Scotland may be explained by higher mortality from causes other than cancer.

  7. Carbonic Anhydrase IX is Not a Predictor of Outcomes in Non-Metastatic Clear Cell Renal Cell Carcinoma - A Digital Analysis of Tissue Microarray

    Directory of Open Access Journals (Sweden)

    Marcelo Zerati

    2013-07-01

    Full Text Available Introduction The knowledge about the molecular biology of clear cell renal cell carcinoma (ccRCC is evolving, and Carbonic Anhydrase type IX (CA-IX has emerged as a potential prognostic marker in this challenging disease. However, most of the literature about CA-IX on ccRCC comes from series on metastatic cancer, with a lack of series on non-metastatic cancer. The objective is to evaluate the expression of CA-IX in a cohort of non-metastatic ccRCC, correlating with 1 overall survival, and 2 with established prognostic parameters (T stage, tumor size, Fuhrman nuclear grade, microvascular invasion and peri-renal fat invasion. Materials and Methods This is a retrospective cohort study. We evaluated 95 patients with non-metastatic clear cell renal cell carcinoma, as to the expression of CA-IX. The analyzed parameters where: overall survival (OS, TNM stage, tumor size (TS, Fuhrman nuclear grade (FNG, microvascular invasion (MVI, peri-renal fat invasion (PFI. We utilized a custom built tissue microarray, and the immunoexpression was digitally quantified using the Photoshop® software. Results: Th e mean follow-up time was 7.9 years (range 1.9 to 19.5 years. The analysis of CA-IX expression against the selected prognostic parameters showed no correlation. The results are as follows: Overall survival (p = 0.790; T stage (p = 0.179; tumor size (p = 0.143; grouped Fuhrman nuclear grade (p = 0.598; microvascular invasion (p = 0.685, and peri-renal fat invasion (p = 0.104. Conclusion Carbonic anhydrase type IX expression does not correlate with overall survival and conventional prognostic parameters in non-metastatic clear cell renal cell carcinoma.

  8. [Clinical significance of signal transduction and activators of transcription 3, E-cadherin and vimentin in colon cancer].

    Science.gov (United States)

    Zhang, Chao; Xu, Jian-Hua; Liu, Tao; Cui, Hao

    2011-03-01

    To evaluate the clinical significance of STAT3, E-cadherin and vimentin in colon cancer. Samples of colon cancer tissue and adjacent normal tissue were procured from 70 patients with colon cancer. The expressions of STAT3, E-cadherin and vimentin were detected by immunohistochemistry. Associations of clinicopathological characteristics and these three factors were evaluated. STAT3, E-cadherin, vimentin were positive in 74.3%,32.9%, and 78.6% in the colon cancer tissues, respectively, and were 15.7%, 82.9%, and 12.9% in normal colon mucosa tissues, respectively. They were correlated with tumor differentiation, depth of invasion, lymph node metastasis, and TNM staging(Pcolon cancer. The expressions of STAT3, E-cadherin and vimentin may serve as prognostic indicators for patients with colon cancer.

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

    Science.gov (United States)

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

    2011-01-01

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

  10. HMG-CoA reductase regulates CCL17-induced colon cancer cell migration via geranylgeranylation and RhoA activation

    International Nuclear Information System (INIS)

    Al-Haidari, Amr A.; Syk, Ingvar; Thorlacius, Henrik

    2014-01-01

    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

  11. Vascular Anatomy in Laparoscopic Colectomy for Right Colon Cancer.

    Science.gov (United States)

    Lee, Sang Jae; Park, Sung Chan; Kim, Min Jung; Sohn, Dae Kyung; Oh, Jae Hwan

    2016-08-01

    The vascular anatomy in the right colon varies; however, related studies are rare, especially on the laparoscopic vascular anatomy of living patients. The purpose of this study was to describe vascular variations around the gastrocolic trunk, middle colic vein, and ileocolic vessels in laparoscopic surgery for right-sided colon cancer. This is a retrospective descriptive study of patients undergoing laparoscopic colectomy for right colon cancer. The study was conducted at a single tertiary institution in Korea. Consecutive patients with right colon cancer who underwent laparoscopic right colectomy using the cranial-to-caudal approach (N = 116) between January 2014 and April 2015 were included. Three colorectal surgeons took photographs and videos of the vascular anatomy during each laparoscopic right colectomy, and these were analyzed for vascular variations. We classified venous variations around the gastrocolic trunk into 2 types (3 subtypes), type 1 (n = 92 (79.3%)), defined as 1 or 2 colic veins draining into the gastrocolic trunk, and type II (n = 24 (20.7%)), defined as having no gastrocolic trunk. We also investigated the tributaries of the superior mesenteric vein. One, 2, and 3 middle colic veins were found in 86 (74.1%), 26 (22.4%), and 4 patients (3.5%). The right colic vein drained directly into the superior mesenteric vein in 22 patients (19.0%). All of the patients had a single ileocolic vein draining into the superior mesenteric vein and a single ileocolic artery from the superior mesenteric artery. The right colic artery from the superior mesenteric artery was present in 38 patients (32.7%). The ileocolic artery passed the superior mesenteric vein anteriorly or posteriorly in 58 patients (50%) each. Unlike cadaver or radiological studies, we could not clarify the complete vessel paths. We classified vascular anatomic variations in laparoscopic colectomy for right colon cancer, which could be helpful for colorectal surgeons.

  12. Triptolide downregulates Rac1 and the JAK/STAT3 pathway and inhibits colitis-related colon cancer progression

    DEFF Research Database (Denmark)

    Wang, Zhipeng; Jin, Haifeng; Xu, Ruodan

    2009-01-01

    ability to block progress of colitis to colon cancer, and its molecular mechanism of action are investigated. A mouse model for colitis-induced colorectal cancer was used to test the effect of triptolide on cancer progression. Treatment of mice with triptolide decreased the incidence of colon cancer...... formation, and increased survival rate. Moreover, triptolide decreased the incidence of tumors in nude mice inoculated with cultured colon cancer cells dose-dependently. In vitro, triptolide inhibited the proliferation, migration and colony formation of colon cancer cells. Secretion of IL6 and levels of JAK....... This suggests that triptolide might be a candidate for prevention of colitis induced colon cancer because it reduces inflammation and prevents tumor formation and development....

  13. MicroRNA classifier and nomogram for metastasis prediction in colon cancer.

    Science.gov (United States)

    Goossens-Beumer, Inès J; Derr, Remco S; Buermans, Henk P J; Goeman, Jelle J; Böhringer, Stefan; Morreau, Hans; Nitsche, Ulrich; Janssen, Klaus-Peter; van de Velde, Cornelis J H; Kuppen, Peter J K

    2015-01-01

    Colon cancer prognosis and treatment are currently based on a classification system still showing large heterogeneity in clinical outcome, especially in TNM stages II and III. Prognostic biomarkers for metastasis risk are warranted as development of distant recurrent disease mainly accounts for the high lethality rates of colon cancer. miRNAs have been proposed as potential biomarkers for cancer. Furthermore, a verified standard for normalization of the amount of input material in PCR-based relative quantification of miRNA expression is lacking. A selection of frozen tumor specimens from two independent patient cohorts with TNM stage II-III microsatellite stable primary adenocarcinomas was used for laser capture microdissection. Next-generation sequencing was performed on small RNAs isolated from colorectal tumors from the Dutch cohort (N = 50). Differential expression analysis, comparing in metastasized and nonmetastasized tumors, identified prognostic miRNAs. Validation was performed on colon tumors from the German cohort (N = 43) using quantitative PCR (qPCR). miR25-3p and miR339-5p were identified and validated as independent prognostic markers and used to construct a multivariate nomogram for metastasis risk prediction. The nomogram showed good probability prediction in validation. In addition, we recommend combination of miR16-5p and miR26a-5p as standard for normalization in qPCR of colon cancer tissue-derived miRNA expression. In this international study, we identified and validated a miRNA classifier in primary cancers, and propose a nomogram capable of predicting metastasis risk in microsatellite stable TNM stage II-III colon cancer. In conjunction with TNM staging, by means of a nomogram, this miRNA classifier may allow for personalized treatment decisions based on individual tumor characteristics. ©2014 American Association for Cancer Research.

  14. Differential Expression of Matrix Metalloproteinase-2 Expression in Disseminated Tumor Cells and Micrometastasis in Bone Marrow of Patients with Nonmetastatic and Metastatic Prostate Cancer: Theoretical Considerations and Clinical Implications—An Immunocytochemical Study

    Directory of Open Access Journals (Sweden)

    Nigel P. Murray

    2012-01-01

    Full Text Available Matrix metalloproteinase-2 (MMP-2 is important in the dissemination and invasion of tumor cells and activates angiogenesis. We present an immunocytochemical study of MMP-2 expression in circulating prostate cells (CPCs, disseminated tumor cells (DTCs, and micrometastasis (mM in bone marrow of men with prostate cancer. Methods and Patients. Tumor cells were identified with anti-PSA immunocytochemistry. Positive samples underwent processing with anti-MMP-2, its expression was compared with Gleason score, concordance of expression, and metastatic and nonmetastatic disease. Results. 215 men participated, CPCs were detected in 62.7%, DTCs in 62.2%, and mM in 71.4% in nonmetastatic cancer; in metastatic cancer all had CPCs, DTCs, and mM detected. All CPCs and DTCs expressed MMP-2; in mM MMP-2 expression was positively associated with increasing Gleason score. MMP-2 expression in CPCs and DTCs showed concordance. In low grade tumors, mM and surrounding stromal cells were MMP-2 negative, with variable expression in high grade tumors; in metastatic disease, both mM and stromal cells were MMP-2 positive. Conclusions. CPCs and DTCs are different from mM, with inhibition of MMP-2 expression in mM of low grade tumors. With disease progression, MMP-2 expression increases in both mM and surrounding stromal cells, with implications for the use of bisphosphonates or MMP-2 inhibitors.

  15. The Akt inhibitor ISC-4 synergizes with cetuximab in 5-FU-resistant colon cancer.

    Directory of Open Access Journals (Sweden)

    Joshua E Allen

    Full Text Available Phenylbutyl isoselenocyanate (ISC-4 is an Akt inhibitor with demonstrated preclinical efficacy against melanoma and colon cancer. In this study, we sought to improve the clinical utility of ISC-4 by identifying a synergistic combination with FDA-approved anti-cancer therapies, a relevant and appropriate disease setting for testing, and biomarkers of response. We tested the activity of ISC-4 and 19 FDA-approved anticancer agents, alone or in combination, against the SW480 and RKO human colon cancer cell lines. A synergistic interaction with cetuximab was identified and validated in a panel of additional colon cancer cell lines, as well as the kinetics of synergy. ISC-4 in combination with cetuximab synergistically reduced the viability of human colon cancer cells with wild-type but not mutant KRAS genes. Further analysis revealed that the combination therapy cooperatively decreased cell cycle progression, increased caspase-dependent apoptosis, and decreased phospho-Akt in responsive tumor cells. The synergism between ISC-4 and cetuximab was retained independently of acquired resistance to 5-FU in human colon cancer cells. The combination demonstrated synergistic anti-tumor effects in vivo without toxicity and in the face of resistance to 5-FU. These results suggest that combining ISC-4 and cetuximab should be explored in patients with 5-FU-resistant colon cancer harboring wild-type KRAS.

  16. Survival and Prognostic Factors for Metachronous Peritoneal Metastasis in Patients with Colon Cancer.

    Science.gov (United States)

    Nagata, Hiroshi; Ishihara, Soichiro; Hata, Keisuke; Murono, Koji; Kaneko, Manabu; Yasuda, Koji; Otani, Kensuke; Nishikawa, Takeshi; Tanaka, Toshiaki; Kiyomatsu, Tomomichi; Kawai, Kazushige; Nozawa, Hiroaki; Watanabe, Toshiaki

    2017-05-01

    The clinical course of metachronous peritoneal metastasis of colorectal origin is poorly understood. In this retrospective study, we aimed to elucidate survival and prognostic factors for metachronous peritoneal metastasis. Patients with metachronous peritoneal metastasis after curative resection for stage I-III colon cancer were retrospectively reviewed, and the incidence and prognosis of metachronous peritoneal metastasis were investigated. Prognostic factors were identified by univariate and multivariate analyses. Among 1582 surgically resected stage I-III colon cancer patients, 65 developed metachronous peritoneal metastasis. The 5-year cumulative incidence rate was 4.5%, and the median survival after diagnosis of peritoneal metastasis was 29.6 months. None of the patients underwent peritonectomy or intraperitoneal chemotherapy. Independent prognostic factors included right colon cancer [hazard ratio (HR) 2.69, 95% confidence interval (CI) 1.26-5.64; p = 0.011], time to metachronous peritoneal metastasis of Cancer Index (PCI) >10 (HR 3.68, 95% CI 1.37-8.99; p = 0.012), concurrent metastases (HR 4.09, 95% CI 2.02-8.23; p colon cancer patients with metachronous peritoneal metastasis may benefit from combined peritoneal nodule resection and systemic chemotherapy. Right colon cancer, early peritoneal metastasis, a high PCI, and concurrent metastases negatively affected prognosis in patients with metachronous peritoneal metastasis.

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

    NARCIS (Netherlands)

    Sesink, ALA; Termont, DSML; Kleibeuker, JH; Van der Meer, R

    2001-01-01

    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

  18. Preoperative serum lipid profile and outcome in nonmetastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Ting-Ting Hong

    2016-12-01

    Full Text Available Objective: A large portion of non-metastatic colorectal cancers (non-mCRCs recur after curative surgery. In addition to the traditional tumor-related factors, host-related factors are also required to accurately predict prognosis. A few studies have shown an association between the serum lipid profile and the survival and treatment response of patients with colorectal cancer. Methods: We retrospectively evaluated the prognostic significance of the preoperative serum lipid profile [total cholesterol (TC, triglyceride (TG, low-density lipoprotein cholesterol (LDL-C, and high-density lipoprotein cholesterol (HDL-C] in patients with non-mCRC treated with curative surgery. The Spearman rank correlation test was used to analyze associations between lipid levels and categorical variables. Lipid levels were modeled as four equal-sized quartiles based on the distribution among the whole cohort. Kaplan-Meier curves were used to estimate survival probabilities, and the log-rank test was used to detect differences between them. Multivariate fractional polynomial (MFP analysis was used to model any non-linear effects and avoid categorization. To evaluate the added prognostic value of lipids, the predictive power of two models (with and without lipids as covariates was compared by using Harrell's C-statistic and the Akaike information criterion (AIC. Results: A total of 266 patients with non-mCRC were enrolled in the present study. Spearman rank correlation test showed that TG levels inversely correlated with N stage (r = −0.20, P = 0.00 and Tumor-Node-Metastasis (TNM stage (r = −0.19, P = 0.00. HDL-C levels positively correlated with perineural invasion (PNI (r = 0.15, P = 0.02, and LDL-C levels inversely correlated with lymphovascular invasion (LVI (r = −0.12, P = 0.04. None of the four lipids predicted overall survival (OS in univariate or multivariate analyses adjusted for age, gender, T stage, N stage, TNM stage

  19. The G-protein coupled chemoattractant receptor FPR2 promotes malignant phenotype of human colon cancer cells

    Science.gov (United States)

    Xiang, Yi; Yao, Xiaohong; Chen, Keqiang; Wang, Xiafei; Zhou, Jiamin; Gong, Wanghua; Yoshimura, Teizo; Huang, Jiaqiang; Wang, Rongquan; Wu, Yuzhang; Shi, Guochao; Bian, Xiuwu; Wang, Jiming

    2016-01-01

    The G-protein coupled chemoattractant receptor formylpeptide receptor-2 (FPR2 in human, Fpr2 in mice) is expressed by mouse colon epithelial cells and plays a critical role in mediating mucosal homeostasis and inflammatory responses. However, the biological role of FPR2 in human colon is unclear. Our investigation revealed that a considerable number of human colon cancer cell lines expressed FPR2 and its ligands promoted cell migration and proliferation. Human colon cancer cell lines expressing high levels of FPR2 also formed more rapidly growing tumors in immunocompromised mice as compared with cell lines expressing lower levels of FPR2. Knocking down of FPR2 from colon cancer cell lines highly expressing FPR2 reduced their tumorigenicity. Clinically, FPR2 is more highly expressed in progressive colon cancer, associated with poorer patient prognosis. These results suggest that FPR2 can be high-jacked by colon cancer cells for their growth advantage, thus becoming a potential target for therapeutic development. PMID:27904774

  20. Increase in intracellular PGE2 induces apoptosis in Bax-expressing colon cancer cell

    International Nuclear Information System (INIS)

    Lalier, Lisenn; Pedelaborde, François; Braud, Christophe; Menanteau, Jean; M Vallette, François; Olivier, Christophe

    2011-01-01

    NSAIDs exhibit protective properties towards some cancers, especially colon cancer. Yet, it is not clear how they play their protective role. PGE 2 is generally shown as the only target of the NSAIDs anticancerous activity. However, PGE 2 known targets become more and more manifold, considering both the molecular pathways involved and the target cells in the tumour. The role of PGE 2 in tumour progression thus appears complex and multipurpose. To gain understanding into the role of PGE 2 in colon cancer, we focused on the activity of PGE 2 in apoptosis in colon cancer cell lines. We observed that an increase in intracellular PGE 2 induced an apoptotic cell death, which was dependent on the expression of the proapoptotic protein Bax. This increase was induced by increasing PGE 2 intracellular concentration, either by PGE 2 microinjection or by the pharmacological inhibition of PGE 2 exportation and enzymatic degradation. We present here a new sight onto PGE 2 in colon cancer cells opening the way to a new prospective therapeutic strategy in cancer, alternative to NSAIDs

  1. Emergency presentation of colon cancer is most frequent during summer.

    Science.gov (United States)

    Gunnarsson, H; Holm, T; Ekholm, A; Olsson, L I

    2011-06-01

    The frequency of emergency colon cancer (ECC) was determined using a reproducible definition of 'emergency' to analyse the impact of mode of presentation on long-term prognosis and to search for risk factors for an emergency presentation. All patients with colon cancer treated at one Swedish GDH between 1996 and 2005 (N = 604) were eligible. Patients admitted through the emergency room, operated on within three days and with an emergency condition confirmed at surgery were classified as ECC. Survival was analysed by Kaplan-Meier estimates and risk of death by Cox regression. The rate of ECC was 97/585 (17%). Patients with ECC were older (median 77 vs 74, P = 0.02), they had more stage III and IV cancers (65%vs 47%; χ(2) = 9.4, P Emergency presentation of colon cancer is an independent and adverse risk factor for long-term survival. The causes of a seasonal variation need to be clarified. © 2011 The Authors. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland.

  2. Diagnostic value of computed tomography in the colon cancer; In terms of the staging system

    International Nuclear Information System (INIS)

    Lee, Joo Mi; Moon, Jang Ho; Lee, Dong Joong; Choi, Chul Soon; Kang, Ik Won; Chung, Soo Young; Bae, Sang Hoon; Yoon, Jong Sub

    1989-01-01

    The CT findings of thirty-three patients with proven colon cancer were analysed. The results were as follows; 1. The accuracy for detecting pericolic fat invasion on CT was 81%. 2. The accuracy for detecting lymph node involvement on CT was 67%. 3. The overall accuracy for staging of colon cancer on CT was 64%(67% for stage A, 30% for stage B, 60% for stage C, 100% for stage D). 4. The overall detection rate of mass on CT was 80%(89% for rectum, 100% for rectosigmoid colon and sigmoid colon, 30% for ascending and transverse colon). 5. The CT is useful, noninvasive technique for assessing extension and staging of colon cancer

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

    Directory of Open Access Journals (Sweden)

    Samir Attoub

    2018-05-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  5. EGF signalling pathway regulates colon cancer stem cell proliferation and apoptosis.

    Science.gov (United States)

    Feng, Y; Dai, X; Li, X; Wang, H; Liu, J; Zhang, J; Du, Y; Xia, L

    2012-10-01

    Cancer stem cells (CSCs) compose a subpopulation of cells within a tumour that can self-renew and proliferate. Growth factors such as epidermal growth factor (EGF) and basic fibroblast growth factor (b-FGF) promote cancer stem cell proliferation in many solid tumours. This study assesses whether EGF, bFGF and IGF signalling pathways are essential for colon CSC proliferation and self-renewal. Colon CSCs were cultured in serum-free medium (SFM) with one of the following growth factors: EGF, bFGF or IGF. Characteristics of CSC gene expression were evaluated by real time PCR. Tumourigenicity of CSCs was determined using a xenograft model in vivo. Effects of EGF receptor inhibitors, Gefitinib and PD153035, on CSC proliferation, apoptosis and signalling were evaluated using fluorescence-activated cell sorting and western blotting. Colon cancer cell HCT116 transformed to CSCs in SFM. Compared to other growth factors, EGF was essential to support proliferation of CSCs that expressed higher levels of progenitor genes (Musashi-1, LGR5) and lower levels of differential genes (CK20). CSCs promoted more rapid tumour growth than regular cancer cells in xenografts. EGFR inhibitors suppressed proliferation and induced apoptosis of CSCs by inhibiting autophosphorylation of EGFR and downstream signalling proteins, such as Akt kinase, extracellular signal-regulated kinase 1/2 (ERK 1/2). This study indicates that EGF signalling was essential for formation and maintenance of colon CSCs. Inhibition of the EGF signalling pathway may provide a useful strategy for treatment of colon cancer. © 2012 Blackwell Publishing Ltd.

  6. Personalizing colon cancer adjuvant therapy: selecting optimal treatments for individual patients.

    Science.gov (United States)

    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. © 2015 by American Society of Clinical Oncology.

  7. Combination of aging and dimethylhydrazine treatment causes an increase in cancer-stem cell population of rat colonic crypts.

    Science.gov (United States)

    Levi, Edi; Misra, Sandhya; Du, Jianhua; Patel, Bhaumik B; Majumdar, Adhip P N

    2009-07-31

    Aging is associated with increased incidence of colon cancers. It is also becoming evident that cancer stem cells (CSC) play a vital role in the pathogenesis and prognosis of colon cancer. Recently, we reported the presence of colon cancer stem-like cells in macroscopically normal mucosa in patients with adenomatous polyps and that they increase with aging, suggesting that aging may predispose the colon to carcinogenesis. In the current study we have examined the combined effects of aging and carcinogen exposure on the status of colon CSCs in an experimental model. We used young (4-6 months) and aged (22-24 months) rats and exposed them to the carcinogen, dimethylhydroxide (DMH). We investigated the expression of colon cancer stem cell markers, CD44, CD166, EpCam, and ALDH1 as well as EGFR expression in normal colonic crypt epithelium following carcinogen treatment. Our results demonstrate that aging per se or carcinogen treatment alone causes an increase in the number of colon cancer stems cells, as evidenced by increased immunoreactive-CSC-markers positive cells in the colonic mucosa. In aged rats, carcinogen exposure results in a more pronounced increase in colon cancer stem cells. Our study shows that in aging colon the effects of carcinogens are more pronounced, and an increase in colon CSCs is one of the earliest changes preceding tumor development. Moreover, the current investigation of the use of a panel of immunohistochemical markers of colon CSC can potentially serve as a prognostic marker during screening for colon cancer.

  8. Positive detection of exfoliated colon cancer cells on linear stapler cartridges was associated with depth of tumor invasion and preoperative bowel preparation in colon cancer.

    Science.gov (United States)

    Ikehara, Kishiko; Endo, Shungo; Kumamoto, Kensuke; Hidaka, Eiji; Ishida, Fumio; Tanaka, Jun-Ichi; Kudo, Shin-Ei

    2016-08-31

    The aim of this study was to investigate exfoliated cancer cells (ECCs) on linear stapler cartridges used for anastomotic sites in colon cancer. We prospectively analyzed ECCs on linear stapler cartridges used for anastomosis in 100 colon cancer patients who underwent colectomy. Having completed the functional end-to-end anastomosis, the linear stapler cartridges were irrigated with saline, which was collected for cytological examination and cytological diagnoses were made by board-certified pathologists based on Papanicolaou staining. The detection rate of ECCs on the linear stapler cartridges was 20 %. Positive detection of ECCs was significantly associated with depth of tumor invasion (p = 0.012) and preoperative bowel preparation (p = 0.003). There were no marked differences between ECC-positive and ECC-negative groups in terms of the operation methods, tumor location, histopathological classification, and surgical margins. Since ECCs were identified on the cartridge of the linear stapler used for anastomosis, preoperative mechanical bowel preparation using polyethylene glycol solution and cleansing at anastomotic sites using tumoricidal agents before anastomosis may be necessary to decrease ECCs in advanced colon cancer.

  9. Adiposity, mediating biomarkers and risk of colon cancer in the european prospective investigation into cancer and nutrition study

    NARCIS (Netherlands)

    Aleksandrova, K.; Drogan, D.; Boeing, H.; Jenab, M.; Bueno de Mesquita, H.B.; Duijnhoven, van F.J.B.

    2014-01-01

    Adiposity is a risk factor for colon cancer, but underlying mechanisms are not well understood. We evaluated the extent to which 11 biomarkers with inflammatory and metabolic actions mediate the association of adiposity measures, waist circumference (WC) and body mass index (BMI), with colon cancer

  10. Metabolic Syndrome X and Colon Cancer

    Czech Academy of Sciences Publication Activity Database

    Matoulek, M.; Svobodová, S.; Svačina, Š.; Plavcová, Marie; Zvárová, Jana; Visokai, V.; Lipská, M.

    2003-01-01

    Roč. 27, suppl. 1 (2003), s. 86 ISSN 0307-0565. [European Congress on Obesity /12./. 29.05.2003-01.06.2003, Helsinki] R&D Projects: GA MZd NB6635; GA MŠk LN00B107 Keywords : metabolic syndrome X * colon cancer Subject RIV: BB - Applied Statistics, Operational Research

  11. Characteristics of [18F] fluorodeoxyglucose uptake in human colon cancer cells

    International Nuclear Information System (INIS)

    Kim, Chae Kyun; Chung, June Key; Jeong, Jae Min; Lee, Myung Chul; Koh, Chang Soon

    1997-01-01

    Cancer tissues are characterized by increased glucose uptake. 18 F-fluorodeoxyglucose(FDG), a glucose analogue is used for the diagnosis of cancer in PET studies. This study was aimed to compare the glucose uptake and glucose transporter 1(GLUT1) expression in various human colon cancer cells. We measured FDG uptake by cell retention study and expression of GLUT1 using Western blotting. Human colon cancer cells, SNU-C2A, SNU-C4 and SNU-C5, were used. The cells were incubated with 1μ Ci/ml of FDG in HEPES- buffered saline for one hour. The FDG uptake of SNU-C2A, SNU-C4 and SNU-C5 were 16.8±1.36, 12.3±5.55 and 61.0±2.17 cpm/μg of protein, respectively. Dose-response and time-course studies represent that FDG uptake of cancer cells were dose dependent and time dependent. The rate of FDG uptake of SNU-C2A, SNU-C4 and SNU-C5 were 0.29±0.03, 0.21±0.09 and 1.07±0.07 cpm/min/μg of protein, respectively. Western blot analysis showed that the GLUT1 expression of SNU-C5 was significantly higher than those of SNU-C2A and SNU-C4. These results represent that FDG uptake into human colon cancer cells are different from each other. In addition, FDG uptake and expression of GLUT1 are closely related in human colon cancer cells

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

    Science.gov (United States)

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

    2018-02-01

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

  13. Efficient intracellular delivery of 5-fluorodeoxyuridine into colon cancer cells by targeted immunoliposomes

    NARCIS (Netherlands)

    Koning, GA; Kamps, JAAM; Scherphof, GL

    2002-01-01

    Immunoliposomes, liposomes with monoclonal antibodies attached, are being developed for targeting the anti-cancer drug 5-fluoro-2'-deoxyuridine (FUdR) to colon cancer cells. A monoclonal antibody against the rat colon carcinoma CC531 was covalently coupled to liposomes containing a dipalmitoylated

  14. Additional prognostic factors in right colon cancer staging.

    Science.gov (United States)

    Parmeggiani, Domenico; Avenia, Nicola; Gubitosi, Adelmo; Gilio, Francesco; Atelli, Pietro Francesco; Agresti, Massimo

    2011-09-01

    Based on the theory--which is now acknowledged-of a clinical difference between proximal and distal colon cancer and on the results of recent genetic and microbiological studies, a minority of authors have assumed that also in the sphere of right-sided colon cancer, tumors at three different locations, namely, the cecum and ascending and transverse colon, can be considered to be biologically different. These studies have provided the basis for a retrospective study carried out on 50 patients admitted to our department from 1996 to 2008 for tumor pathology of the right colon. The tumor was considered to be a unified biological entity and assessed in relation to the three above-mentioned locations. The results verify that the aggressive of the tumor increases from the cecum to the transverse, with a higher percentage of cecal tumors being in I stage, more tumors in the ascending colon being in II stage, and more transverse tumors, with the largest percentage of N+ and M+, in stages III and IV. This difference in biological behavior for the three tumor locations has been also found in terms of sensitiveness, both pre- and post-operation, of tumor markers CEA, TPA, and CA19-9. Clinical data revealed a binary relationship between the transverse, cecum, and ascending tumors, which ultimately affects patient mortality, which increases in a directly proportional way from the cecum to the transverse-in the case of a tumor at one of these locations.

  15. TAp63 suppress metastasis via miR-133b in colon cancer cells.

    Science.gov (United States)

    Lin, C W; Li, X R; Zhang, Y; Hu, G; Guo, Y H; Zhou, J Y; Du, J; Lv, L; Gao, K; Zhang, Y; Deng, H

    2014-04-29

    TAp63 is a tumour-suppressor protein that is often underexpressed in various types of cancer. It has been shown to activate gene transcription depending on the transcription domain and to be closely related with metastasis. In this study, we demonstrate that TAp63 suppresses metastasis in colon cancer cells through microRNA-133b. We evaluated the correlation of TAp63 and miR-133b with HT-29 and SW-620 cells and investigated the roles of TAp63 in the expression of RhoA, E-cadherin and vimentin. We further investigated the roles of TAp63-mediated invasion and migration of colon cancer cells. TAp63 expression is downregulated in colon cancer, and microRNA-133b is a transcriptional target of TAp63. Furthermore, microRNA-133b is essential for the inhibitory effects of TAp63 on RhoA, E-cadherin and vimentin. Moreover, TAp63 inhibits cell migration and invasion through microRNA-133b. Correspondingly, the inhibitory effect of TAp63 on RhoA, E-cadherin, vimentin, migration and invasion can be blocked by the microRNA-133b inhibitor. TAp63 and microRNA-133b were able to suppress the metastasis of colon cancer. Both TAp63 and microRNA-133b may be potential biomarkers for diagnosis in colon cancer metastasis and may provide unique therapeutic targets for this common malignancy.

  16. Reviewing the Management of Obstructive Left Colon Cancer: Assessing the Feasibility of the One-stage Resection and Anastomosis After Intraoperative Colonic Irrigation.

    Science.gov (United States)

    Awotar, Gavish Kumar; Guan, Guoxin; Sun, Wei; Yu, Hongliang; Zhu, Ming; Cui, Xinye; Liu, Jie; Chen, Jiaxi; Yang, Baoshun; Lin, Jianyu; Deng, Zeyong; Luo, Jianwei; Wang, Chen; Nur, Osman Abdifatah; Dhiman, Pankaj; Liu, Pixu; Luo, Fuwen

    2017-06-01

    The management of obstructive left colon cancer (OLCC) remains debatable with the single-stage procedure of primary colonic anastomosis after cancer resection and on-table intracolonic lavage now being supported. Patients with acute OLCC who were admitted between January 2008 and January 2015 were distributed into 5 different groups. Group ICI underwent emergency laparotomy for primary anastomosis following colonic resection and intraoperative colonic lavage; Group HP underwent emergency Hartmann's Procedure; Group CON consisted of patients treated by conservative management with subsequent elective open cancer resection; Group COL were colostomy patients; and Group INT consisted of patients who had interventional radiology followed by open elective colon cancer resection. The demographics of the patients and comorbidity, intraoperative data, and postoperative data were collected, with P  .05). Group INT and Group CON, when compared to the three surgical groups, Groups ICI, Group COL, and Group HP, individually, were statistically significant for the duration of surgery (P irrigation can be safely performed in selected patients, with the necessary surgical expertise, with no increased risk in mortality, anastomotic leakage, and other postoperative complications. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Different effects of ERβ and TROP2 expression in Chinese patients with early-stage colon cancer.

    Science.gov (United States)

    Fang, Yu-Jing; Wang, Guo-Qiang; Lu, Zhen-Hai; Zhang, Lin; Li, Ji-Bin; Wu, Xiao-Jun; Ding, Pei-Rong; Ou, Qing-Jian; Zhang, Mei-Fang; Jiang, Wu; Pan, Zhi-Zhong; Wan, De-Sen

    2012-12-01

    Estrogen receptor beta (ERβ) and TROP2 expressed in colon carcinoma and might play an important role there. We explored the relationship of ERβ and TROP2 expression with the prognosis of early-stage colon cancer. ERβ and TROP2 levels were assessed by immunohistochemistry in normal mucosa and tumoral tissues from 220 Chinese patients with T(3)N(0)M(0) (stage IIa) and T(4)N(0)M(0) (stage IIb) colon cancer in the Cancer Center, Sun Yat-sen University, who underwent curative surgical resection between 1995 and 2003. The Cox proportional hazards regression model was applied to analyze the overall survival (OS) data, and the ROC curve, Kaplan-Meier estimate, log rank test, and Jackknife method were used to show the effect of ERβ and TROP2 expression at different stages of cancer. The 5-year survival rates were not significantly different between the patients with stage IIa and stage IIb colon cancer (83 vs. 80 %, respectively). The high expression of ERβ was related to decreasing OS in stage IIa and stage IIb colon cancer, while the high expression of TROP2 was related to decreasing OS in stage IIb colon cancer. The expression of ERβ and TROP2 has tumor-suppressive and tumor-promoting effect in stage IIa and stage IIb colon cancer, respectively.

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

    Directory of Open Access Journals (Sweden)

    Shan Wang

    2016-03-01

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  20. A novel NSAID derivative, phospho-ibuprofen, prevents AOM-induced colon cancer in rats

    Science.gov (United States)

    OUYANG, NENGTAI; JI, PING; WILLIAMS, JENNIE L.

    2013-01-01

    The cancer chemopreventive properties and gastrointestinal toxicity of ibuprofen are well documented. Modification of existing NSAIDs has improved on the chemopreventive efficacy of this agent and reduced its toxicity. In this study, ibuprofen and a modified derivative (phospho-modified ibuprofen or p-ibuprofen) were used in a chemically induced model of colon cancer. Fisher 344 rats were injected with azoxymethane then treated with either ibuprofen (500 ppm) or p-ibuprofen (900 ppm) for 20 weeks to observe aberrant crypt foci (ACF) or 40 weeks to evaluate tumor incidence and multiplicity. β-catenin and p65 were measured in colonic tissues by immunofluorescence staining. Equal molar doses of ibuprofen (75 and 670 mg/kg) and p-ibuprofen (135 and 1,215 mg/kg) were administered to rats for 7 days to assess acute toxicity. The in vitro effect of p-ibuprofen on COX-2 and PGE2 synthesis, β-catenin expression and NF-κB activity were examined in RAW 264.7 macrophage and HCT 116 colon cancer cells. At week 20, p-ibuprofen and ibuprofen significantly reduced the multiplicity of ACF compared with control (pibuprofen and ibuprofen reduced the multiplicity of colon tumors compared with control (pibuprofen (670 mg/kg) and p-ibuprofen (1,215 mg/kg) resulted in stomach ulceration in 85.7% (6 out of 7) and 14.3% (1 out of 7) of rats, respectively, with pibuprofen and p-ibuprofen suppressed β-catenin nuclear translocation in colon cancer cells. In addition, p-ibuprofen but not ibuprofen inhibited NF-κB activation in colon cancer cells. Collectively, these results suggest that p-ibuprofen is a potential effective novel drug for long-term use in colon cancer prevention. PMID:23291777

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

    Science.gov (United States)

    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

  2. Tumor-stroma ratio predicts recurrence in patients with colon cancer treated with neoadjuvant chemotherapy

    DEFF Research Database (Denmark)

    Hansen, Torben Frøstrup; Kjær-Frifeldt, Sanne; Lindebjerg, Jan

    2017-01-01

    BACKGROUND: Neoadjuvant chemotherapy represents a new treatment approach to locally advanced colon cancer. The aim of this study was to analyze the ability of tumor-stroma ratio (TSR) to predict disease recurrence in patients with locally advanced colon cancer treated with neoadjuvant chemotherapy....... MATERIAL AND METHODS: This study included 65 patients with colon cancer treated with neoadjuvant chemotherapy in a phase II trial. All patients were planned for three cycles of capecitabine and oxaliplatin before surgery. Hematoxylin and eosin stained tissue sections from surgically resected primary tumors...... was 55%, compared to 94% in the group of patients with a high TSR. CONCLUSIONS: TSR assessed in the surgically resected primary tumor from patients with locally advanced colon cancer treated with neoadjuvant chemotherapy provides prognostic value and may serve as a relevant parameter in selecting...

  3. Mucin expression patterns in histological grades of colonic cancers ...

    African Journals Online (AJOL)

    Pathological expression of mucins has been noted in cancer development and progression. This study sought to identify and quantify the types of mucins produced during various histological grades of colon cancer and to assess the diagnostic significance. Methods: Formalin fixed, paraffin-embedded tissue blocks, ...

  4. High mortality rates after nonelective colon cancer resection : results of a national audit

    NARCIS (Netherlands)

    Bakker, I. S.; Snijders, H. S.; Grossmann, I.; Karsten, T. M.; Havenga, K.; Wiggers, T.

    AimColon cancer resection in a nonelective setting is associated with high rates of morbidity and mortality. The aim of this retrospective study is to identify risk factors for overall mortality after colon cancer resection with a special focus on nonelective resection. MethodData were obtained from

  5. A key role of microRNA-29b for the suppression of colon cancer cell migration by American ginseng.

    Directory of Open Access Journals (Sweden)

    Deepak Poudyal

    Full Text Available Metastasis of colon cancer cells increases the risk of colon cancer mortality. We have recently shown that American ginseng prevents colon cancer, and a Hexane extract of American Ginseng (HAG has particularly potent anti-inflammatory and anti-cancer properties. Dysregulated microRNA (miR expression has been observed in several disease conditions including colon cancer. Using global miR expression profiling, we observed increased miR-29b in colon cancer cells following exposure to HAG. Since miR-29b plays a role in regulating the migration of cancer cells, we hypothesized that HAG induces miR-29b expression to target matrix metalloproteinase-2 (MMP-2 thereby suppressing the migration of colon cancer cells. Results are consistent with this hypothesis. Our study supports the understanding that targeting MMP-2 by miR-29b is a mechanism by which HAG suppresses the migration of colon cancer cells.

  6. The novel HDAC inhibitor AR-42-induced anti-colon cancer cell activity is associated with ceramide production

    International Nuclear Information System (INIS)

    Xu, Weihong; Xu, Bin; Yao, Yiting; Yu, Xiaoling; Shen, Jie

    2015-01-01

    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

  7. The novel HDAC inhibitor AR-42-induced anti-colon cancer cell activity is associated with ceramide production

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Weihong; Xu, Bin; Yao, Yiting; Yu, Xiaoling [Department of Clinical Laboratory, Tongren Hospital, Shanghai (China); Shen, Jie, E-mail: tongrensj163@163.com [Department of Administrative, Tongren Hospital, No. 786 Yuyuan Road, Changning District, Shanghai (China)

    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.

  8. The use of minimal preparation computed tomography for the primary investigation of colon cancer in frail or elderly patients

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, Philip; Burnett, Hugh; Nicholson, David A

    2002-05-01

    AIM: To assess the place of computed tomography (CT) of the colon in frail or elderly patients with symptoms suggestive of colon cancer. METHOD: A total of 195 patients (median age 76 years) underwent CT of the abdomen and pelvis following the administration of positive oral contrast medium but no bowel preparation. All had symptoms suggestive of colon cancer. CT findings were classified as normal/diverticular disease (DD), possible colon cancer, definite colon cancer or extracolonic pathology. Accuracy of CT was assessed against patient outcome. Association between symptoms and colon cancer was assessed by chi-squared test. RESULTS: There were 47 deaths and median follow up for those alive was 16 months. Overall sensitivity of CT was 100% and specificity 87% for detection of colon cancer. One hundred and ten normal/DD CT examinations had no significant bowel lesion on follow up. Of 12 cases defined as 'definite cancers' on CT, there were nine colon cancers, two extracolonic cancers, and one normal. Of 23 'possible cancers' on CT, there were two colon cancers, three DD masses and 18 normal/DD. Fifty examinations had extracolonic findings including 33 (17%) cases of significant abdominal disease. CT findings led to a halt in investigations in 115 cases (59%), colonoscopy in 18 (9%) cases and surgery in 16 (8%) cases. None of the symptoms present showed a significant association with colon cancer (all P > 0.05). CONCLUSION: Minimal preparation CT is a non-invasive and sensitive method for investigating colon cancer in frail or elderly patients. It has a 100% negative predictive value and also detects a large number of extracolonic lesions. Robinson, P. et al. (2002)

  9. The use of minimal preparation computed tomography for the primary investigation of colon cancer in frail or elderly patients

    International Nuclear Information System (INIS)

    Robinson, Philip; Burnett, Hugh; Nicholson, David A.

    2002-01-01

    AIM: To assess the place of computed tomography (CT) of the colon in frail or elderly patients with symptoms suggestive of colon cancer. METHOD: A total of 195 patients (median age 76 years) underwent CT of the abdomen and pelvis following the administration of positive oral contrast medium but no bowel preparation. All had symptoms suggestive of colon cancer. CT findings were classified as normal/diverticular disease (DD), possible colon cancer, definite colon cancer or extracolonic pathology. Accuracy of CT was assessed against patient outcome. Association between symptoms and colon cancer was assessed by chi-squared test. RESULTS: There were 47 deaths and median follow up for those alive was 16 months. Overall sensitivity of CT was 100% and specificity 87% for detection of colon cancer. One hundred and ten normal/DD CT examinations had no significant bowel lesion on follow up. Of 12 cases defined as 'definite cancers' on CT, there were nine colon cancers, two extracolonic cancers, and one normal. Of 23 'possible cancers' on CT, there were two colon cancers, three DD masses and 18 normal/DD. Fifty examinations had extracolonic findings including 33 (17%) cases of significant abdominal disease. CT findings led to a halt in investigations in 115 cases (59%), colonoscopy in 18 (9%) cases and surgery in 16 (8%) cases. None of the symptoms present showed a significant association with colon cancer (all P > 0.05). CONCLUSION: Minimal preparation CT is a non-invasive and sensitive method for investigating colon cancer in frail or elderly patients. It has a 100% negative predictive value and also detects a large number of extracolonic lesions. Robinson, P. et al. (2002)

  10. Secreted Human Adipose Leptin Decreases Mitochondrial Respiration in HCT116 Colon Cancer Cells

    Science.gov (United States)

    Yehuda-Shnaidman, Einav; Nimri, Lili; Tarnovscki, Tanya; Kirshtein, Boris; Rudich, Assaf; Schwartz, Betty

    2013-01-01

    Obesity is a key risk factor for the development of colon cancer; however, the endocrine/paracrine/metabolic networks mediating this connection are poorly understood. Here we hypothesize that obesity results in secreted products from adipose tissue that induce malignancy-related metabolic alterations in colon cancer cells. Human HCT116 colon cancer cells, were exposed to conditioned media from cultured human adipose tissue fragments of obese vs. non-obese subjects. Oxygen consumption rate (OCR, mostly mitochondrial respiration) and extracellular acidification rate (ECAR, mostly lactate production via glycolysis) were examined vis-à-vis cell viability and expression of related genes and proteins. Our results show that conditioned media from obese (vs. non-obese) subjects decreased basal (40%, prespiration and function in HCT116 colon cancer cells, an effect that is at least partly mediated by leptin. These results highlight a putative novel mechanism for obesity-associated risk of gastrointestinal malignancies, and suggest potential new therapeutic avenues. PMID:24073224

  11. PHENOTYPIC FEATURES OF ENDOMETRIAL CANCER AND MSI IN COLON AND BLOOD SERUM

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    S. M. Kartashov

    2014-04-01

    Full Text Available Since the end of the last century an upward trend regarding hormone-dependent tumours of the reproductive system, including endometrial cancer (EC has been observed, with one of the trend reasons being increased number of mutations, in particular, microsatellite instability (MSI – the consequence of unpaired nucleotides repair system gene inactivation (MSH2, MSH3, MSH6, MLH1,PMS2, EXO1. This molecular genetic phenomenon may also be characteristic of certain colon cancer forms, while being detectable not only in the tumour but also in blood, which may be of clinical interest as regards either determining risk groups in terms of other localization malignant tumours development, especially colon cancer, or early diagnostics of the said diseases. However, relationship between clinical, phenotypic and molecular risk factors for EC and colon cancer needs further studying. The aim of research – to estimate MSI frequency in blood serum and colonic mucosal lining in patients with EC. Materials and methods. 342 patients with I – IV stage EC aged between 30 and 80 underwent MSI determining in tumour tissue, blood serum and colonic mucosa by means of polymerase chain reaction method using primers for microsatellite sequence (ВАТ-25, ВАТ-26. Colonic mucosal lining samples were obtained by colonoscopy prior to surgical intervention. Genomic DNA purification from blood serum was performed using DNA purification kit produced by Silex M Scientific and Production Company (Russia, in accordance with manufacturer's instructions. PCR was performed by the standard procedure using Tertsik-2 programmable thermal cycler produced by DNA – Technology LTD, Russia. The studies were carried out at Virola laboratory at Kharkiv Medical Academy of Postgraduate Education. Ethics and Bioethics Committee permit (minutes No.4 of 18.04.2013, Kharkiv Medical Academy of Postgraduate Education. The obtained digital study results were processed by means of conventional

  12. Functional heterogeneity of cancer-associated fibroblasts from human colon tumors shows specific prognostic gene expression signature.

    Science.gov (United States)

    Herrera, Mercedes; Islam, Abul B M M K; Herrera, Alberto; Martín, Paloma; García, Vanesa; Silva, Javier; Garcia, Jose M; Salas, Clara; Casal, Ignacio; de Herreros, Antonio García; Bonilla, Félix; Peña, Cristina

    2013-11-01

    Cancer-associated fibroblasts (CAF) actively participate in reciprocal communication with tumor cells and with other cell types in the microenvironment, contributing to a tumor-permissive neighborhood and promoting tumor progression. The aim of this study is the characterization of how CAFs from primary human colon tumors promote migration of colon cancer cells. Primary CAF cultures from 15 primary human colon tumors were established. Their enrichment in CAFs was evaluated by the expression of various epithelial and myofibroblast specific markers. Coculture assays of primary CAFs with different colon tumor cells were performed to evaluate promigratory CAF-derived effects on cancer cells. Gene expression profiles were developed to further investigate CAF characteristics. Coculture assays showed significant differences in fibroblast-derived paracrine promigratory effects on cancer cells. Moreover, the association between CAFs' promigratory effects on cancer cells and classic fibroblast activation or stemness markers was observed. CAF gene expression profiles were analyzed by microarray to identify deregulated genes in different promigratory CAFs. The gene expression signature, derived from the most protumorogenic CAFs, was identified. Interestingly, this "CAF signature" showed a remarkable prognostic value for the clinical outcome of patients with colon cancer. Moreover, this prognostic value was validated in an independent series of 142 patients with colon cancer, by quantitative real-time PCR (qRT-PCR), with a set of four genes included in the "CAF signature." In summary, these studies show for the first time the heterogeneity of primary CAFs' effect on colon cancer cell migration. A CAF gene expression signature able to classify patients with colon cancer into high- and low-risk groups was identified.

  13. Adjuvant Chemotherapy for Stage II Colon Cancer: A Clinical Dilemma.

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    Kannarkatt, Joseph; Joseph, Joe; Kurniali, Peter C; Al-Janadi, Anas; Hrinczenko, Borys

    2017-04-01

    The decision to treat a patient with stage II colon cancer with adjuvant chemotherapy can be challenging. Although the benefit of treatment is clear in most patients with stage III disease, the decision to provide chemotherapy after surgical resection in stage II disease must be made on an individual basis. Several trials have demonstrated the small but absolute benefits of receiving adjuvant chemotherapy for stage II colon cancer for disease-free survival and overall survival. In an attempt to better understand the role of chemotherapy, several studies were performed that identified high-risk characteristics that can be used prognostically and predictively to aid in the clinical decision making process. ASCO, the National Comprehensive Cancer Network, and the European Society of Medical Oncology have published guidelines describing these high-risk characteristics. Since then, several other molecular markers have emerged that may offer more information on a given patient's risk for recurrence. The decision to treat a patient with stage II colon cancer must be made on an individual basis, considering the risks and benefits of treatment. In this short review, we will present the available evidence and offer possible directions for future study.

  14. Radiosensitization effects of sorafenib on colon cancer cells

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    Kim, Eun Ho; Kim, Mi-Sook; Jung, Won-Gyun; Jeong, Youn Kyoung [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2014-11-15

    Radiotherapy is a standard therapy in the adjuvant treatment of resected colon and rectum cancers, and its combination with chemotherapy has been shown to reduce local failure and distant metastasis still further, thereby improving the outcome of treatment. One potential chemotherapeutic agent for this, sorafenib (Nexavar, BAY43-9006), is an oral multikinase inhibitor that blocks tumor cell proliferation and angiogenesis, and induces tumor cell apoptosis by inhibiting serine/threonine kinases (c-RAF and mutant and wild-type BRAF) as well as the receptor tyrosine kinases vascular endothelial growth factor receptor 2 and 3 (VEGFR2 and VEGFR3), platelet- derived growth factor receptor , FLT3, and c-KIT. Sorafenib is currently used in clinics to treat patients with advanced renal cell carcinoma, hepatocellular carcinoma, and thyroid cancer. These findings provide a molecular evidence base for the use of chemoradiation to treat colon cancer, and in vivo modeling should be used to further assess its suitability for clinical applications.

  15. Overexpression of GRK3, Promoting Tumor Proliferation, Is Predictive of Poor Prognosis in Colon Cancer

    Directory of Open Access Journals (Sweden)

    Tao Jiang

    2017-01-01

    Full Text Available Deregulation of G protein-coupled receptor kinase 3 (GRK3, which belongs to a subfamily of kinases called GRKs, acts as a promoter mechanism in some cancer types. Our study found that GRK3 was significantly overexpressed in 162 pairs of colon cancer tissues than in the matched noncancerous mucosa (P<0.01. Based on immunohistochemistry staining of TMAs, GRK3 was dramatically stained positive in primary colon cancer (130/180, 72.22%, whereas it was detected minimally or negative in paired normal mucosa specimens (50/180, 27.78%. Overexpression of GRK3 was closely correlated with AJCC stage (P=0.001, depth of tumor invasion (P<0.001, lymph node involvement (P=0.004, distant metastasis (P=0.016, and histologic differentiation (P=0.004. Overexpression of GRK3 is an independent prognostic indicator that correlates with poor survival in colon cancer patients. Consistent with this, downregulation of GRK3 exhibited decreased cell growth index, reduction in colony formation ability, elevated cell apoptosis rate, and impaired colon tumorigenicity in a xenograft model. Hence, a specific overexpression of GRK3 was observed in colon cancer, GRK3 potentially contributing to progression by mediating cancer cell proliferation and functions as a poor prognostic indicator in colon cancer and potentially represent a novel therapeutic target for the disease.

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

    OpenAIRE

    Prieto, Isabel; del Puerto-Nevado, Laura; Gonzalez, Nieves; Portal-Nu?ez, 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

    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...

  17. Integrin α6Bβ4 inhibits colon cancer cell proliferation and c-Myc activity

    International Nuclear Information System (INIS)

    Dydensborg, Anders Bondo; Teller, Inga C; Groulx, Jean-François; Basora, Nuria; Paré, Fréderic; Herring, Elizabeth; Gauthier, Rémy; Jean, Dominique; Beaulieu, Jean-François

    2009-01-01

    Integrins are known to be important contributors to cancer progression. We have previously shown that the integrin β4 subunit is up-regulated in primary colon cancer. Its partner, the integrin α6 subunit, exists as two different mRNA splice variants, α6A and α6B, that differ in their cytoplasmic domains but evidence for distinct biological functions of these α6 splice variants is still lacking. In this work, we first analyzed the expression of integrin α6A and α6B at the protein and transcript levels in normal human colonic cells as well as colorectal adenocarcinoma cells from both primary tumors and established cell lines. Then, using forced expression experiments, we investigated the effect of α6A and α6B on the regulation of cell proliferation in a colon cancer cell line. Using variant-specific antibodies, we observed that α6A and α6B are differentially expressed both within the normal adult colonic epithelium and between normal and diseased colonic tissues. Proliferative cells located in the lower half of the glands were found to predominantly express α6A, while the differentiated and quiescent colonocytes in the upper half of the glands and surface epithelium expressed α6B. A relative decrease of α6B expression was also identified in primary colon tumors and adenocarcinoma cell lines suggesting that the α6A/α6B ratios may be linked to the proliferative status of colonic cells. Additional studies in colon cancer cells showed that experimentally restoring the α6A/α6B balance in favor of α6B caused a decrease in cellular S-phase entry and repressed the activity of c-Myc. The findings that the α6Bβ4 integrin is expressed in quiescent normal colonic cells and is significantly down-regulated in colon cancer cells relative to its α6Aβ4 counterpart are consistent with the anti-proliferative influence and inhibitory effect on c-Myc activity identified for this α6Bβ4 integrin. Taken together, these findings point out the importance of integrin

  18. Association Among Blood Transfusion, Sepsis, and Decreased Long-term Survival After Colon Cancer Resection.

    Science.gov (United States)

    Aquina, Christopher T; Blumberg, Neil; Becerra, Adan Z; Boscoe, Francis P; Schymura, Maria J; Noyes, Katia; Monson, John R T; Fleming, Fergal J

    2017-08-01

    To investigate the potential additive effects of blood transfusion and sepsis on colon cancer disease-specific survival, cardiovascular disease-specific survival, and overall survival after colon cancer surgery. Perioperative blood transfusions are associated with infectious complications and increased risk of cancer recurrence through systemic inflammatory effects. Furthermore, recent studies have suggested an association among sepsis, subsequent systemic inflammation, and adverse cardiovascular outcomes. However, no study has investigated the association among transfusion, sepsis, and disease-specific survival in postoperative patients. The New York State Cancer Registry and Statewide Planning and Research Cooperative System were queried for stage I to III colon cancer resections from 2004 to 2011. Propensity-adjusted survival analyses assessed the association of perioperative allogeneic blood transfusion, sepsis, and 5-year colon cancer disease-specific survival, cardiovascular disease-specific survival, and overall survival. Among 24,230 patients, 29% received a transfusion and 4% developed sepsis. After risk adjustment, transfusion and sepsis were associated with worse colon cancer disease-specific survival [(+)transfusion: hazard ratio (HR) 1.19, 95% confidence interval (CI) 1.09-1.30; (+)sepsis: HR 1.84, 95% CI 1.44-2.35; (+)transfusion/(+)sepsis: HR 2.27, 95% CI 1.87-2.76], cardiovascular disease-specific survival [(+)transfusion: HR 1.18, 95% CI 1.04-1.33; (+)sepsis: HR 1.63, 95% CI 1.14-2.31; (+)transfusion/(+)sepsis: HR 2.04, 95% CI 1.58-2.63], and overall survival [(+)transfusion: HR 1.21, 95% CI 1.14-1.29; (+)sepsis: HR 1.76, 95% CI 1.48-2.09; (+)transfusion/(+)sepsis: HR 2.36, 95% CI 2.07-2.68] relative to (-)transfusion/(-)sepsis. Additional analyses suggested an additive effect with those who both received a blood transfusion and developed sepsis having even worse survival. Perioperative blood transfusions are associated with shorter survival

  19. Activins and their related proteins in colon carcinogenesis: insights from early and advanced azoxymethane rat models of colon cancer.

    Science.gov (United States)

    Refaat, Bassem; El-Shemi, Adel Galal; Mohamed, Amr Mohamed; Kensara, Osama Adnan; Ahmad, Jawwad; Idris, Shakir

    2016-11-11

    Activin-A may exert pro- or anti-tumorigenic activities depending on cellular context. However, little is known about its role, or the other mature activin proteins, in colorectal carcinoma (CRC). This study measured the expression of activin βA- & βB-subunits, activin type IIA & IIB receptors, smads 2/3/4/6/7 and follistatin in CRC induced by azoxymethane (AOM) in rats. The results were compared with controls and disseminated according to the characteristics of histopathological lesions. Eighty male Wistar rats were allocated into 20 controls and the remaining were equally divided between short 'S-AOM' (15 weeks) and long 'L-AOM' (35 weeks) groups following injecting AOM for 2 weeks. Subsequent to gross and histopathological examinations and digital image analysis, the expression of all molecules was measured by immunohistochemistry and quantitative RT-PCR. Activin-A, activin-B, activin-AB and follistatin were measured by ELISA in serum and colon tissue homogenates. Colonic pre-neoplastic and cancerous lesions were identified in both AOM groups and their numbers and sizes were significantly (P colonic epithelial cells. There was a significantly (P cancerous tissues. Oppositely, a significant (P colonic lesions. Normal rat colon epithelial cells are capable of synthesising, controlling as well as responding to activins in a paracrine/autocrine manner. Colonic activin systems are pathologically altered during tumorigenesis and appear to be time and lesion-dependent. Activins could also be potential sensitive markers and/or molecular targets for the diagnosis and/or treatment of CRC. Further studies are required to illustrate the clinical value of activins and their related proteins in colon cancer.

  20. Elevated serum levels of MMP-11 correlate with poor prognosis in colon cancer patients.

    Science.gov (United States)

    Pang, Li; Wang, Da-Wei; Zhang, Nan; Xu, Da-Hai; Meng, Xiang-Wei

    2016-03-11

    Matrix metalloproteinase 11 (MMP11) has been shown to play a key role in human tumor progression and indicates poor clinical outcome in cancer patients. The current study aimed to evaluate the relationship between serum levels of MMP-11 and prognosis in colon cancer patients. Serum levels of MMP-11 were determined in 92 colon cancer patients and 92 healthy individuals using an enzyme-linked immunosorbent assay (ELISA). Associations between serum MMP-11 levels and clinicopathological characteristics of the patients and their outcomes were investigated. Survival analyses were performed to measure the 5-year overall survival (OS) and disease-free survival (DFS). Serum MMP-11 levels were substantially higher in colon cancer patients than in healthy controls. Moreover, serum MMP-11 levels were significantly higher in patients with advanced T status, lymph node metastasis, distant metastasis, and a higher TNM stage. Elevated serum levels of MMP-11 were identified as an independent prognostic factor for 5-year mortality and adverse events associated with colon cancer. Multivariate Cox regression analysis identified the serum MMP-11 level as an independent predictor of OS and DFS. Our study established that high serum levels of MMP-11 are associated with poor clinical outcome and may serve as a prognostic biomarker in colon cancer patients.

  1. A Case of Advanced Descending Colon Cancer in an Adult Patient with Intestinal Malrotation

    Directory of Open Access Journals (Sweden)

    Yoshifumi Nakayama

    2016-01-01

    Full Text Available This report presents an operative case of advanced descending colon cancer in an adult patient with intestinal malrotation. A 63-year-old Japanese male was suffering from left side abdominal pain, abdominal distension, and constipation. An endoscopic examination revealed an advanced tumor in the descending colon. Computed tomography (CT of the abdomen revealed the thickening of the descending colon wall and superior mesenteric vein rotation. An opaque enema detected severe stenosis of the descending colon. An abdominal X-ray examination revealed the dilation of the colon and small intestine with niveau. At the insertion of an ileus tube, the C-loop of the duodenum was observed to be absent and the small intestine was located on the right side of the abdomen. After the decompression of the bowel contents, laparotomy was performed. Descending colon cancer was observed to have directly invaded the left side of the transverse colon. Left hemicolectomy, lymph node dissection, and appendectomy were performed. The patient had an uneventful recovery and was discharged from the hospital on the 16th day after surgery. This report presents a rare operative case of descending colon cancer in an adult patient with intestinal malrotation.

  2. Identifying colon cancer risk modules with better classification performance based on human signaling network.

    Science.gov (United States)

    Qu, Xiaoli; Xie, Ruiqiang; Chen, Lina; Feng, Chenchen; Zhou, Yanyan; Li, Wan; Huang, Hao; Jia, Xu; Lv, Junjie; He, Yuehan; Du, Youwen; Li, Weiguo; Shi, Yuchen; He, Weiming

    2014-10-01

    Identifying differences between normal and tumor samples from a modular perspective may help to improve our understanding of the mechanisms responsible for colon cancer. Many cancer studies have shown that signaling transduction and biological pathways are disturbed in disease states, and expression profiles can distinguish variations in diseases. In this study, we integrated a weighted human signaling network and gene expression profiles to select risk modules associated with tumor conditions. Risk modules as classification features by our method had a better classification performance than other methods, and one risk module for colon cancer had a good classification performance for distinguishing between normal/tumor samples and between tumor stages. All genes in the module were annotated to the biological process of positive regulation of cell proliferation, and were highly associated with colon cancer. These results suggested that these genes might be the potential risk genes for colon cancer. Copyright © 2013. Published by Elsevier Inc.

  3. Complement 5a stimulates macrophage polarization and contributes to tumor metastases of colon cancer.

    Science.gov (United States)

    Piao, Chunmei; Zhang, Wen-Mei; Li, Tao-Tao; Zhang, Cong-Cong; Qiu, Shulan; Liu, Yan; Liu, Sa; Jin, Ming; Jia, Li-Xin; Song, Wen-Chao; Du, Jie

    2018-05-15

    Inflammatory cells such as macrophages can play a pro-tumorigenic role in the tumor stroma. Tumor-associated macrophages (TAMs) generally display an M2 phenotype with tumor-promoting activity; however, the mechanisms regulating the TAM phenotype remain unclear. Complement 5a (C5a) is a cytokine-like polypeptide that is generated during complement system activation and is known to promote tumor growth. Herein, we investigated the role of C5a on macrophage polarization in colon cancer metastasis in mice. We found that deficiency of the C5a receptor (C5aR) severely impairs the metastatic ability of implanted colon cancer cells. C5aR was expressed on TAMs, which exhibited an M2-like functional profile in colon cancer liver metastatic lesions. Furthermore, C5a mediated macrophage polarization and this process relied substantially on activation of the nuclear factor-kappa B (NF-κB) pathway. Finally, analysis of human colon carcinoma indicated that C5aR expression is negatively associated with tumor differentiation grade. Our results demonstrate that C5aR has a central role in regulating the M2 phenotype of TAMs, which in turn, contributes to hepatic metastasis of colon cancer through NF-κB signaling. C5a is a potential novel marker for cancer prognosis and drugs targeting complement system activation, specifically the C5aR pathway, may offer new therapeutic opportunities for colon cancer management. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. The Potential Use of N-Myristoyltransferase as a Biomarker in the Early Diagnosis of Colon Cancer

    International Nuclear Information System (INIS)

    Kumar, Sujeet; Dimmock, Jonathan R; Sharma, Rajendra K

    2011-01-01

    Colon cancer is one of the most common malignant diseases and a major cause of mortality in the Western world. Metastasis to lymph nodes and other gastrointestinal organs, especially to the liver and lungs, is most common and occurs in up to 25% of cancer patients when initially diagnosed. The majority of colon cancers develop from noncancerous adenomatous polyps on the lining of the colon which grow over the years to become cancerous. If detected early, the surgical resections of the growth, often in combination with chemotherapy, significantly increases life expectancy. We have shown that the enzyme N-myristoyltransferase (NMT) which carries out lipid modification of several proteins (including many of those involved in oncogenesis) is expressed at higher levels in cancerous tissues from the colon. We have also shown that in peripheral blood mononuclear cells (PBMC) and bone marrow (BM) cells collected from colon cancer patients and from azoxymethane-induced rats the expression and localization of NMT is altered. We have observed strong positivity for NMT in immunohistochemical analysis for PBMC from colon cancer patients as compared to control groups. Furthermore, in the bone marrow (BM) mononuclear cells, NMT was found to be confined to the nuclei whereas in control groups it was observed to be located in the cytoplasm. In conclusion, this strikingly differential localization offers the basis of a potential investigational tool for screening or diagnosis of individuals at risk for or suspected of having colon cancer

  5. Molecular Basis of Alcohol-Related Gastric and Colon Cancer.

    Science.gov (United States)

    Na, Hye-Kyung; Lee, Ja Young

    2017-05-24

    Many meta-analysis, large cohort studies, and experimental studies suggest that chronic alcohol consumption increases the risk of gastric and colon cancer. Ethanol is metabolized by alcohol dehydrogenases (ADH), catalase or cytochrome P450 2E1 (CYP2E1) to acetaldehyde, which is then further oxidized to acetate by aldehyde dehydrogenase (ALDH). Acetaldehyde has been classified by the International Agency for Research on Cancer (IARC) as a Group 1 carcinogen to humans. The acetaldehyde level in the stomach and colon is locally influenced by gastric colonization by Helicobacter pylori or colonic microbes, as well as polymorphisms in the genes encoding tissue alcohol metabolizing enzymes, especially ALDH2. Alcohol stimulates the uptake of carcinogens and their metabolism and also changes the composition of enteric microbes in a way to enhance the aldehyde level. Alcohol also undergoes chemical coupling to membrane phospholipids and disrupts organization of tight junctions, leading to nuclear translocation of β-catenin and ZONAB, which may contributes to regulation of genes involved in proliferation, invasion and metastasis. Alcohol also generates reactive oxygen species (ROS) by suppressing the expression of antioxidant and cytoprotective enzymes and inducing expression of CYP2E1 which contribute to the metabolic activation of chemical carcinogens. Besides exerting genotoxic effects by directly damaging DNA, ROS can activates signaling molecules involved in inflammation, metastasis and angiogenesis. In addition, alcohol consumption induces folate deficiency, which may result in aberrant DNA methylation profiles, thereby influencing cancer-related gene expression.

  6. Non-metastatic 2 (NME2)-mediated suppression of lung cancer metastasis involves transcriptional regulation of key cell adhesion factor vinculin

    Science.gov (United States)

    Thakur, Ram Krishna; Yadav, Vinod Kumar; Kumar, Akinchan; Singh, Ankita; Pal, Krishnendu; Hoeppner, Luke; Saha, Dhurjhoti; Purohit, Gunjan; Basundra, Richa; Kar, Anirban; Halder, Rashi; Kumar, Pankaj; Baral, Aradhita; Kumar, MJ Mahesh; Baldi, Alfonso; Vincenzi, Bruno; Lorenzon, Laura; Banerjee, Rajkumar; Kumar, Praveen; Shridhar, Viji; Mukhopadhyay, Debabrata; Chowdhury, Shantanu

    2014-01-01

    Tumor metastasis refers to spread of a tumor from site of its origin to distant organs and causes majority of cancer deaths. Although >30 metastasis suppressor genes (MSGs) that negatively regulate metastasis have been identified so far, two issues are poorly understood: first, which MSGs oppose metastasis in a tumor type, and second, which molecular function of MSG controls metastasis. Herein, integrative analyses of tumor-transcriptomes (n = 382), survival data (n = 530) and lymph node metastases (n = 100) in lung cancer patients identified non-metastatic 2 (NME2) as a key MSG from a pool of >30 metastasis suppressors. Subsequently, we generated a promoter-wide binding map for NME2 using chromatin immunoprecipitation with promoter microarrays (ChIP-chip), and transcriptome profiling. We discovered novel targets of NME2 which are involved in focal adhesion signaling. Importantly, we detected binding of NME2 in promoter of focal adhesion factor, vinculin. Reduced expression of NME2 led to enhanced transcription of vinculin. In comparison, NME1, a close homolog of NME2, did not bind to vinculin promoter nor regulate its expression. In line, enhanced metastasis of NME2-depleted lung cancer cells was found in zebrafish and nude mice tumor models. The metastatic potential of NME2-depleted cells was remarkably diminished upon selective RNA-i-mediated silencing of vinculin. Together, we demonstrate that reduced NME2 levels lead to transcriptional de-repression of vinculin and regulate lung cancer metastasis. PMID:25249619

  7. The differential impact of microsatellite instability as a marker of prognosis and tumour response between colon cancer and rectal cancer.

    Science.gov (United States)

    Hong, Sung Pil; Min, Byung So; Kim, Tae Il; Cheon, Jae Hee; Kim, Nam Kyu; Kim, Hoguen; Kim, Won Ho

    2012-05-01

    Microsatellite instability (MSI) is a distinct molecular phenotype of colorectal cancer related to prognosis and tumour response to 5-fluorouracil (5-FU)-based chemotherapy. We investigated the differential impact of MSI between colon and rectal cancers as a marker of prognosis and chemotherapeutic response. PCR-based MSI assay was performed on 1125 patients. Six hundred and sixty patients (58.7%) had colon cancer and 465 patients (41.3%) had rectal cancer. Among 1125 patients, 106 (9.4%) had high-frequency MSI (MSI-H) tumours. MSI-H colon cancers (13%) had distinct phenotypes including young age at diagnosis, family history of colorectal cancer, early Tumor, Node, Metastasis (TNM) stage, proximal location, poor differentiation, and high level of baseline carcinoembryonic antigen (CEA), while MSI-H rectal cancers (4.3%) showed similar clinicopathological characteristics to MSS/MSI-L tumours except for family history of colorectal cancer. MSI-H tumours were strongly correlated with longer disease free survival (DFS) (P=0.005) and overall survival (OS) (P=0.009) than MSS/MSI-L tumours in colon cancer, while these positive correlations were not observed in rectal cancers. The patients with MSS/MSI-L tumours receiving 5-FU-based chemotherapy showed good prognosis (P=0.013), but this positive association was not observed in MSI-H (P=0.104). These results support the use of MSI status as a marker of prognosis and response to 5-FU-based chemotherapy in patients with colon cancers. Further study is mandatory to evaluate the precise role of MSI in patients with rectal cancers and the effect of 5-FU-based chemotherapy in MSI-H tumours. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    Ostenfeld, Eva B; Erichsen, Rune; Iversen, Lene H; Gandrup, Per; Nørgaard, Mette; Jacobsen, Jacob

    2011-01-01

    Objective The prognosis for colon and rectal cancer has improved in Denmark over the past decades but is still poor compared with that in our neighboring countries. We conducted this population-based study to monitor recent trends in colon and rectal cancer survival in the central and northern regions of Denmark. Material and methods Using the Danish National Registry of Patients, we identified 9412 patients with an incident diagnosis of colon cancer and 5685 patients diagnosed with rectal cancer between 1998 and 2009. We determined survival, and used Cox proportional hazard regression analysis to compare mortality over time, adjusting for age and gender. Among surgically treated patients, we computed 30-day mortality and corresponding mortality rate ratios (MRRs). Results The annual numbers of colon and rectal cancer increased from 1998 through 2009. For colon cancer, 1-year survival improved from 65% to 70%, and 5-year survival improved from 37% to 43%. For rectal cancer, 1-year survival improved from 73% to 78%, and 5-year survival improved from 39% to 47%. Men aged 80+ showed most pronounced improvements. The 1- and 5-year adjusted MRRs decreased: for colon cancer 0.83 (95% confidence interval CI: 0.76–0.92) and 0.84 (95% CI: 0.78–0.90) respectively; for rectal cancer 0.79 (95% CI: 0.68–0.91) and 0.81 (95% CI: 0.73–0.89) respectively. The 30-day postoperative mortality after resection also declined over the study period. Compared with 1998–2000 the 30-day MRRs in 2007–2009 were 0.68 (95% CI: 0.53–0.87) for colon cancer and 0.59 (95% CI: 0.37–0.96) for rectal cancer. Conclusion The survival after colon and rectal cancer has improved in central and northern Denmark during the 1998–2009 period, as well as the 30-day postoperative mortality. PMID:21814467

  9. Association of sedentary behaviour with colon and rectal cancer: a meta-analysis of observational studies.

    Science.gov (United States)

    Cong, Y J; Gan, Y; Sun, H L; Deng, J; Cao, S Y; Xu, X; Lu, Z X

    2014-02-04

    Sedentary behaviour is ubiquitous in modern society. Emerging studies have focused on the health consequences of sedentary behaviour, including colorectal cancer, but whether sedentary behaviour is associated with the risks of colon and rectal cancer remains unclear. No systematic reviews have applied quantitative techniques to independently compute summary risk estimates. We aimed to conduct a meta-analysis to investigate this issue. We searched PubMed, Embase, and Google Scholar databases up to May 2013 to identify cohort and case-control studies that evaluated the association between sedentary behaviour and colon or rectal cancer. A random-effect model was used to pool the results of included studies. Publication bias was assessed by using Begg's funnel plot. Twenty-three studies with 63 reports were included in our meta-analysis. These groups included 4,324,462 participants (27,231 colon cancer cases and 13,813 rectal cancer cases). Sedentary behaviour was significantly associated with colon cancer (relative risk (RR): 1.30, 95% confidence interval (CI): 1.22-1.39) but did not have a statistically significant association with rectal cancer (RR 1.05, 95% CI, 0.98-1.13). Subgroup analyses suggested that the odds ratio (OR) of colon cancer was 1.46 (95% CI: 1.22-1.68) in the case-control studies, and the RR was 1.27 (95% CI: 1.18-1.36) in the cohort studies, the OR of rectal cancer was 1.06 (95% CI: 0.85-1.33) in the case-control studies, and the RR was 1.06 (95% CI, 1.01-1.12) in the cohort studies. Sedentary behaviour is associated with an increased risk of colon cancer. Subgroup analyses suggest a positive association between sedentary behaviour and risk of rectal cancer in cohort studies. Reducing sedentary behaviour is potentially important for the prevention of colorectal cancer.

  10. Possible better long-term survival in left versus right-sided colon cancer - a systematic review

    DEFF Research Database (Denmark)

    Hansen, Iben Onsberg; Jess, Per

    2012-01-01

    Colon cancer is one of the most frequent types of cancer in Denmark and the western world. Recent studies indicate that there are differences between right- and left-sided colon cancer with regard to epidemiology, clinical manifestation, pathology and prognosis. The present systematic literature...

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

    Directory of Open Access Journals (Sweden)

    Hatoh Shinji

    2009-03-01

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

  12. Anastomotic Recurrence of Sigmoid Colon Cancer over Five Years after Surgery

    Directory of Open Access Journals (Sweden)

    Takahiro Yamauchi

    2013-10-01

    Full Text Available The incidence of anastomotic recurrence after curative resection of colorectal cancer is relatively low compared to that of other types of recurrence, such as hepatic, lung and local recurrence. However, almost all cases of anastomotic recurrence of colorectal cancer occur within 3 years after surgery. We experienced a rare case of anastomotic recurrence in whom colonoscopy revealed no signs of recurrence 3 years after surgery; however, anastomotic recurrence was detected over 5 years after surgery. A 60-year-old female with a history of surgery for cancer of the cecum in her forties underwent sigmoidectomy and right colectomy with D3 lymph node dissection for both stage IIA sigmoid colon cancer and stage IIA transverse colon cancer. Computed tomography and colonoscopy revealed no signs of recurrence 3 years after surgery; however, 5 years and 4 months after surgery, colonoscopy demonstrated surrounding flaring and swelling in the anastomotic area of the sigmoid colon, and a biopsy revealed an adenocarcinoma. Under the diagnosis of anastomotic recurrence over 5 years after surgery, lower anterior resection was performed. The patient has exhibited no other signs of recurrence in the 2 years since the last operation.

  13. Trypanosomiasis-induced megacolon illustrates how myenteric neurons modulate the risk for colon cancer in rats and humans.

    Directory of Open Access Journals (Sweden)

    Vinicius Kannen

    2015-04-01

    Full Text Available 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.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.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.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.

  14. Roles of stromal microenvironment in colon cancer progression.

    Science.gov (United States)

    Taketo, Makoto Mark

    2012-05-01

    Although our understanding of epithelial cancer cells has advanced significantly, our understanding of the cancer microenvironment is still fragmentary. In contrast to our intuitive impression that our body always suppresses cancer growth, recent pieces of evidence show that cancer often exploits our body reactions to expand, invade local tissues and metastasize to distant organs. Accordingly, investigations of such body reactions in the tumour microenvironment should help us to design novel therapeutic strategies that can be combined with the traditional therapeutics targeted at the cancer cells themselves. In this article, I am going to review our recent efforts in search of novel therapeutic strategies against colon cancer using mouse models.

  15. Aberrant expression of sonic hedgehog pathway in colon cancer and melanosis coli.

    Science.gov (United States)

    Wang, Zhong Chuan; Gao, Jun; Zi, Shu Ming; Yang, Ming; Du, Peng; Cui, Long

    2013-08-01

    To determine the hedgehog (Hh) signaling pathway correlated with the development of colon cancer and melanosis coli. Protein and mRNA levels of Hh signaling pathway components (sonic hedgehog [Shh], protein patched homolog 1 [Ptch 1], GLI family zinc finger 1 [Gli 1] and suppressor of fused homolog [Drosophila] [Sufu]) in 127 patients with colon cancer, 36 with melanosis coli and 20 adjacent normal mucosal tissues taken from surgical specimens were evaluated using antibody staining and quantitative real-time polymerase chain reaction. In adjacent normal tissue Shh and Ptch1, but not Gli1 or Sufu, were weakly expressed and mainly in the lining epithelium of the colonic mucosa. In cancerous tissues Shh and Gli1 were uniformly strong while Ptch1 was patchy and weak, and Sufu uniformly weak, which paralleled their levels of corresponding mRNA. Elevated protein levels of Shh and Ptch were significantly associated with mucinous colonic tissues. Elevated Sufu protein levels were positively correlated with the diameter and invasion of the tumor. In patients with melanosis coli, mRNA levels of Shh, Ptch1, Gli1 and Sufu were very low, which was similar to those of adjacent normal tissues; but protein levels of Shh, Ptch1 and Gli1, but not Sufu, were high, which was similar to those of cancerous tissues. The mRNA and protein levels of Hh pathway components are aberrantly elevated in colon cancer, which may be the potential molecular classification markers. Further studies are required to determine the role of melanosis coli in the colon tumorigenesis. © 2013 The Authors. Journal of Digestive Diseases © 2013 Wiley Publishing Asia Pty Ltd and Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine.

  16. Fem1b, a proapoptotic protein, mediates proteasome inhibitor-induced apoptosis of human colon cancer cells.

    Science.gov (United States)

    Subauste, M Cecilia; Sansom, Owen J; Porecha, Nehal; Raich, Natacha; Du, Liqin; Maher, Joseph F

    2010-02-01

    In the treatment of colon cancer, the development of resistance to apoptosis is a major factor in resistance to therapy. New molecular approaches to overcome apoptosis resistance, such as selectively upregulating proapoptotic proteins, are needed in colon cancer therapy. In a mouse model with inactivation of the adenomatous polyposis coli (Apc) tumor suppressor gene, reflecting the pathogenesis of most human colon cancers, the gene encoding feminization-1 homolog b (Fem1b) is upregulated in intestinal epithelium following Apc inactivation. Fem1b is a proapoptotic protein that interacts with apoptosis-inducing proteins Fas, tumor necrosis factor receptor-1 (TNFR1), and apoptotic protease activating factor-1 (Apaf-1). Increasing Fem1b expression induces apoptosis of cancer cells, but effects on colon cancer cells have not been reported. Fem1b is a homolog of feminization-1 (FEM-1), a protein in Caenorhabditis elegans that is regulated by proteasomal degradation, but whether Fem1b is likewise regulated by proteasomal degradation is unknown. Herein, we found that Fem1b protein is expressed in primary human colon cancer specimens, and in malignant SW620, HCT-116, and DLD-1 colon cancer cells. Increasing Fem1b expression, by transfection of a Fem1b expression construct, induced apoptosis of these cells. We found that proteasome inhibitor treatment of SW620, HCT-116, and DLD-1 cells caused upregulation of Fem1b protein levels, associated with induction of apoptosis. Blockade of Fem1b upregulation with morpholino antisense oligonucleotide suppressed the proteasome inhibitor-induced apoptosis of these cells. In conclusion, the proapoptotic protein Fem1b is downregulated by the proteasome in malignant colon cancer cells and mediates proteasome inhibitor-induced apoptosis of these cells. Therefore, Fem1b could represent a novel molecular target to overcome apoptosis resistance in therapy of colon cancer.

  17. SOLITARY SPLENIC METASTASIS OF COLON CANCER: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Sh. Hashemzadeh M. Safari

    2004-11-01

    Full Text Available Although splenic metastasis is fairly common in disseminated cancer, solitary splenic metastasis in the absence of diffuse dissemination is rare. We report a case of 44 year-old man who developed isolated splenic metastasis of colon cancer. The patient had undergone right sided hemicolectomy for colon cancer in 1988. In 2001, he underwent reoperation because of local recurrence of tumor in the anastomotic site. The patient was admitted to our hospital on Sep 2003 with abdominal pain. Chest X-ray was normal. Abdominal CT scan showed a large cystic lesion in the spleen. Splenectomy was performed for the patient. The spleen was enlarged, firm and irregular. Histological examination showed metastatic mucinous adenocarcinoma. Based on this case, we recommend that clinicians consider possibility of metastasis in cystic lesions of spleen, especially in patients with a history of a malignant disease.

  18. Trametinib and TAS-102 in Treating Patients With Colon or Rectal Cancer That is Advanced, Metastatic, or Cannot Be Removed by Surgery

    Science.gov (United States)

    2018-04-13

    RAS Family Gene Mutation; Stage III Colon Cancer AJCC v7; Stage III Colorectal Cancer AJCC v7; Stage III Rectal Cancer AJCC v7; Stage IIIA Colon Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIA Rectal Cancer AJCC v7; Stage IIIB Colon Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIB Rectal Cancer AJCC v7; Stage IIIC Colon Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IIIC Rectal Cancer AJCC v7; Stage IV Colon Cancer AJCC v7; Stage IV Colorectal Cancer AJCC v7; Stage IV Rectal Cancer AJCC v7; Stage IVA Colon Cancer AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVA Rectal Cancer AJCC v7; Stage IVB Colon Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7; Stage IVB Rectal Cancer AJCC v7

  19. ZEB1 Promotes Oxaliplatin Resistance through the Induction of Epithelial - Mesenchymal Transition in Colon Cancer Cells.

    Science.gov (United States)

    Guo, Cao; Ma, Junli; Deng, Ganlu; Qu, Yanlin; Yin, Ling; Li, Yiyi; Han, Ying; Cai, Changjing; Shen, Hong; Zeng, Shan

    2017-01-01

    Background: Oxaliplatin (OXA) chemotherapy is widely used in the clinical treatment of colon cancer. However, chemo-resistance is still a barrier to effective chemotherapy in cases of colon cancer. Accumulated evidence suggests that the epithelial mesenchymal transition (EMT) may be a critical factor in chemo-sensitivity. The present study investigated the effects of Zinc finger E-box binding homeobox 1 (ZEB1) on OXA-sensitivity in colon cancer cells. Method: ZEB1expression and its correlation with clinicopathological characteristics were analyzed using tumor tissue from an independent cohort consisting of 118 colon cancer (CC) patients who receiving OXA-based chemotherapy. ZEB1 modulation of OXA-sensitivity in colon cancer cells was investigated in a OXA-resistant subline of HCT116/OXA cells and the parental colon cancer cell line: HCT116. A CCK8 assay was carried out to determine OXA-sensitivity. qRT-PCR, Western blot, Scratch wound healing and transwell assays were used to determine EMT phenotype of colon cells. ZEB1 knockdown using small interfering RNA (siRNA) was used to determine the ZEB1 contribution to OXA-sensitivity in vitro and in vivo (in a nude mice xenograft model). Result: ZEB1 expression was significantly increased in colon tumor tissue, and was correlated with lymph node metastasis and the depth of invasion. Compared with the parental colon cancer cells (HCT116), HCT116/OXA cells exhibited an EMT phenotype characterized by up-regulated expression of ZEB1, Vimentin, MMP2 and MMP9, but down-regulated expression of E-cadherin. Transfection of Si-ZEB1 into HCT116/OXA cells significantly reversed the EMT phenotype and enhanced OXA-sensitivity in vitro and in vivo . Conclusion: HCT116/OXA cells acquired an EMT phenotype. ZEB1 knockdown effectively restored OXA-sensitivity by reversing EMT. ZEB1 is a potential therapeutic target for the prevention of OXA-resistance in colon cancer.

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

    NARCIS (Netherlands)

    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.

    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

  1. Small invasive colon cancer with systemic metastasis: A case report

    Directory of Open Access Journals (Sweden)

    Sakamoto Taku

    2011-05-01

    Full Text Available ABSTRACT Background Recently, especially in Japan, several researchers have suggested that colorectal cancer can develop not only through an adenoma-carcinoma sequence but also from normal mucosa via a de novo pathway, and that these de novo cancers have more aggressive malignant potential. We report a case of aggressive colon cancer resulting in systemic metastasis despite small tumour size. Case Presentation A 35-year-old woman presented at the referring hospital with swelling of the left cervical lymph node. Biopsy of the lymph node revealed metastatic adenocarcinoma; however, CT scan and mammography were unable to identify the site of the primary lesion. She was diagnosed with unknown primary cancer and referred to our hospital for further examination. Immunohistochemical reevaluation showed the cervical lymph node biopsy specimen to be positive for CDX2 and CK20 and negative for CK7 expression, leading us to suspect the presence of a primary colorectal cancer. We performed a total colonoscopy, and detected a small protruding lesion in the transverse colon. The tumour was only 12 mm in diameter, with a central depressed component and a severely thickened stalk, which suggested direct cancer invasion of the deep submucosa. We concluded that this lesion was the site of origin of the metastasis despite the small tumour size, and performed diagnostic endoscopic mucosal resection. The lesion was found to have an intramucosal cancer component, demonstrating that this lesion represented primary colon cancer. The patient was referred to the gastrointestinal oncology division for systemic chemotherapy. Conclusions In this case, immunohistochemical findings strongly suggested the existence of a colorectal cancer. The non-polypoid gross appearance of the tumour suggested that it can originate de novo , thus providing a valuable case in support of the aggressive malignant potential of a de novo colorectal cancer pathway.

  2. The 2016 Assisi Think Tank Meeting on breast cancer: white paper

    DEFF Research Database (Denmark)

    Aristei, Cynthia; Kaidar-Person, Orit; Arenas, Meritxell

    2016-01-01

    PURPOSE: To identify weak points in daily routine use of radiation therapy (RT) for non-metastatic breast cancer patients, particularly when data are lacking or equivocal, a "think tank" of experts met in Assisi. METHODS: Before the meeting, controversial issues on non-metastatic breast cancer were...

  3. The 2016 Assisi Think Tank Meeting on breast cancer: white paper

    NARCIS (Netherlands)

    Aristei, C.; Kaidar-Person, O.; Arenas, M.; Coles, C.; Offersen, B.V.; Bourgier, C.; Frezza, G.; Leonardi, M.C.; Valentini, V.; Poortmans, P.M.P.

    2016-01-01

    PURPOSE: To identify weak points in daily routine use of radiation therapy (RT) for non-metastatic breast cancer patients, particularly when data are lacking or equivocal, a "think tank" of experts met in Assisi. METHODS: Before the meeting, controversial issues on non-metastatic breast cancer were

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

    Directory of Open Access Journals (Sweden)

    Molly Marie Derry

    2013-05-01

    Full Text Available 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; ~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 positively 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.

  5. [A Case of Transverse Colon Cancer Metastasized to the Spermatic Cord after Resection of Peritoneal Dissemination].

    Science.gov (United States)

    Kikuchi, Isao; Kimura, Tomoaki; Azuma, Saya; Shimbo, Tomonori; Wakabayashi, Toshiki; Ota, Sakae; Sato, Tsutomu; Itoh, Seiji; Ishida, Toshiya; Sageshima, Masato

    2017-11-01

    We report a rare case of spermatic cord metastasis from colon cancer. A man in his 50s underwent extended right hemicolectomy for transverse colon cancer followed by resection of a peritoneal recurrence. After receiving adjuvant chemotherapy for 6 months, he became aware of a right inguinal mass. A spermatic cord tumor was noted on computed tomography(CT) and FDG/PET-CT. He underwent radical orchiectomy. The resected tumor was histologically compatible with the colon cancer. Although he received additional chemotherapy, right inguinal recurrence was resected 6 months after orchiectomy. Colon cancer is the second most common origin, after gastric cancer, of metastatic spermatic tumor. As several metastatic routes have been reported, peritoneal seeding is mostly suspected in this case.

  6. Human Colon Tumors Express a Dominant-Negative Form of SIGIRR That Promotes Inflammation and Colitis-Associated Colon Cancer in Mice.

    Science.gov (United States)

    Zhao, Junjie; Bulek, Katarzyna; Gulen, Muhammet F; Zepp, Jarod A; Karagkounis, Georgio; Martin, Bradley N; Zhou, Hao; Yu, Minjia; Liu, Xiuli; Huang, Emina; Fox, Paul L; Kalady, Matthew F; Markowitz, Sanford D; Li, Xiaoxia

    2015-12-01

    Single immunoglobulin and toll-interleukin 1 receptor (SIGIRR), a negative regulator of the Toll-like and interleukin-1 receptor (IL-1R) signaling pathways, controls intestinal inflammation and suppresses colon tumorigenesis in mice. However, the importance of SIGIRR in human colorectal cancer development has not been determined. We investigated the role of SIGIRR in development of human colorectal cancer. We performed RNA sequence analyses of pairs of colon tumor and nontumor tissues, each collected from 68 patients. Immunoblot and immunofluorescence analyses were used to determine levels of SIGIRR protein in primary human colonic epithelial cells, tumor tissues, and colon cancer cell lines. We expressed SIGIRR and mutant forms of the protein in Vaco cell lines. We created and analyzed mice that expressed full-length (control) or a mutant form of Sigirr (encoding SIGIRR(N86/102S), which is not glycosylated) specifically in the intestinal epithelium. Some mice were given azoxymethane (AOM) and dextran sulfate sodium to induce colitis-associated cancer. Intestinal tissues were collected and analyzed by immunohistochemical and gene expression profile analyses. RNA sequence analyses revealed increased expression of a SIGIRR mRNA isoform, SIGIRR(ΔE8), in colorectal cancer tissues compared to paired nontumor tissues. SIGIRR(ΔE8) is not modified by complex glycans and is therefore retained in the cytoplasm-it cannot localize to the cell membrane or reduce IL1R signaling. SIGIRR(ΔE8) interacts with and has a dominant-negative effect on SIGIRR, reducing its glycosylation, localization to the cell surface, and function. Most SIGIRR detected in human colon cancer tissues was cytoplasmic, whereas in nontumor tissues it was found at the cell membrane. Mice that expressed SIGIRR(N86/102S) developed more inflammation and formed larger tumors after administration of azoxymethane and dextran sulfate sodium than control mice; colon tissues from these mutant mice expressed

  7. Intraoperative Tumor Perforation is Associated with Decreased 5-Year Survival in Colon Cancer

    DEFF Research Database (Denmark)

    Bundgaard, N S; Bendtsen, V O; Ingeholm, P

    2017-01-01

    BACKGROUND: It is a widely held belief that intraoperative tumor perforation in colon cancer impairs survival and causes local recurrence, although the prognostic importance remains unclear. AIM: The aim of this study was to assess the effect of unintended intraoperative tumor perforation...... on postoperative mortality and long-term survival. MATERIAL AND METHODS: This national cohort study was based on data from a prospectively maintained nationwide colorectal cancer database. We included 16,517 colon cancer patients who were resected with curative intent from 2001 to 2012. RESULTS: Intraoperative...... tumor perforation produced a significantly impaired 5-year survival of 40% compared to 64% in non-perforated colon cancer. Intraoperative tumor perforation was an independent risk factor for death, hazard ratio 1.63 (95% confidence interval: 1.4-1.94), with a significantly increased 90-day postoperative...

  8. Red meat and colon cancer : how dietary heme initiates hyperproliferation

    NARCIS (Netherlands)

    IJssennagger, N.

    2012-01-01

    Colorectal cancer is a leading cause of cancer deaths in Western countries. The risk to develop colorectal cancer is associated with the intake of red meat. Red meat contains the porphyrin pigment heme. Heme is an irritant for the colonic wall and it is previously shown that the addition of heme

  9. Colon cancer metastasis to the mandibular gingiva with partial occult squamous differentiation: A case report and literature review

    OpenAIRE

    Ren, Quan-Guang; Huang, Tao; Yang, Sheng-Li; Hu, Jian-Li

    2016-01-01

    Metastasis is the primary cause of death among patients with colon cancer. However, the number of available studies regarding oral cavity metastases from colon cancer is currently limited. We herein report an unusual case of a 60-year-old male patient who developed an oral cavity metastasis from colon cancer. A total of 12 clinical case studies reporting colon cancer metastases to the mandibular gingival region were also reviewed, with the aim to elucidate the clinical and pathological charac...

  10. Cecal perforation with an ascending colon cancer caused by upper gastrointestinal endoscopy

    Directory of Open Access Journals (Sweden)

    Hiroyuki Miyatani

    2009-04-01

    Full Text Available Hiroyuki Miyatani1, Yukio Yoshida1, Hirokazu Kiyozaki21Department of Gastroenterology, Jichi Medical University, Saitama Medical Center, Saitama, Japan; 2Department of Surgery, Jichi Medical University, Saitama Medical Center, Saitama, JapanAbstract: Colonic perforation caused by upper gastrointestinal (GI endoscopy is extremely rare. A 69-year-old woman was referred to our hospital because of abdominal fullness. Colonoscopy could be performed only up to the hepatic flexure due to an elongated colon and residual stools. Because her symptoms improved, upper GI endoscopy was performed 11 days later. The patient developed severe abdominal pain two hours after the examination. Abdominal X-ray and computed tomography showed massive free air. Immediate laparotomy was performed for the intestinal perforation. After removal of stool, a perforation site was detected in the cecum with an invasive ascending colon cancer. Therefore, a right hemicolectomy, ileostomy, and transverse colostomy were performed. Although she developed postoperative septicemia, the patient was discharged 38 days after admission. Seven months postoperatively, the patient died of lung, liver, and brain metastases. Even in cases with a lesion that is not completely obstructed, it is important to note that air insufflations during upper GI endoscopy can perforate the intestinal wall in patients with advanced colon cancer.Keywords: colonic perforation, colon cancer, upper gastrointestinal endoscopy, fecal peritonitis

  11. Colon cancer risk and different HRT formulations: a case-control study

    Directory of Open Access Journals (Sweden)

    Thai Do

    2007-05-01

    Full Text Available Abstract Background Most studies have found no increased risk of colon cancer associated with hormone replacement therapy (HRT, or even a decreased risk. But information about the effects of different HRT preparations is lacking. Methods A case-control study was performed within Germany in collaboration with regional cancer registries and tumor centers. Up to 5 controls were matched to each case of colon cancer. Conditional logistic regression analysis was applied to estimate crude and adjusted odds ratios (OR and 95% confidence intervals (95% CI. Stratified analyses were performed to get an impression of the risk associated with different estrogens and progestins. Results A total of 354 cases of colon cancer were compared with 1422 matched controls. The adjusted overall risk estimate for colon cancer (ColC associated with ever-use of HRT was 0.97 (0.71 – 1.32. No clinically relevant trends for ColC risk were observed with increasing duration of HRT use, or increasing time since first or last HRT use in aggregate. Whereas the overall risk estimates were stable, the numbers in many of the sub-analyses of HRT preparation groups (estrogens and progestins were too small for conclusions. Nevertheless, if the ColC risk estimates are taken at face value, most seemed to be reduced compared with never-use of HRT, but did not vary much across HRT formulation subgroups. In particular, no substantial difference in ColC risk was observed between HRT-containing conjugated equine estrogens (CEE or medroxyprogesterone acetate (MPA and other formulations more common in Europe. Conclusion Ever-use of HRT was not associated with an increased risk of colon cancer. In contrary, most risk estimates pointed non-significantly toward a lower ColC risk in HRT ever user. They did not vary markedly among different HRT formulations (estrogens, progestins. However, the small numbers and the overlapping nature of the subgroups suggest cautious interpretation.

  12. Metastatic mucinous adenocarcinoma of the distal common bile duct, from transverse colon cancer presenting as obstructive jaundice.

    Science.gov (United States)

    Lee, Doo-Ho; Ahn, Young Joon; Shin, Rumi; Lee, Hae Won

    2015-08-01

    The patient was a 70-year-old male whose chief complaints were obstructive jaundice and weight loss. Abdominal imaging studies showed a 2.5 cm sized mass at the distal common bile duct, which was suggestive of bile duct cancer. Eccentric enhancing wall thickening in the transverse colon was also shown, suggesting concomitant colon cancer. A colonoscopy revealed a lumen-encircling ulcerofungating mass in the transverse colon, that was pathologically proven to be adenocarcinoma. The bile duct pathology was also adenocarcinoma. Pylorus-preserving pancreaticoduodenectomy and extended right hemicolectomy were performed under the diagnosis of double primary cancers. Postoperative histopathologic examination revealed moderately differentiated mucinous adenocarcinoma of transverse colon cancer, and mucinous adenocarcinoma of the distal common bile duct. Immunohistochemical staining studies showed that the bile duct cancer had metastasized from the colon cancer. The patient recovered uneventfully from surgery and will be undergoing chemotherapy for three months.

  13. diet, bowel motility, faeces composition and colonic cancer

    African Journals Online (AJOL)

    1970-07-20

    Jul 20, 1970 ... The commonness of colonic cancer in privileged popula- tions compared with ... salient differences in environmental factors concern diet. physical activity .... how well known are the risk factors for coronary heart disease; yet ...

  14. ETV4 and Myeov knockdown impairs colon cancer cell line proliferation and invasion

    International Nuclear Information System (INIS)

    Moss, Alan C.; Lawlor, Garrett; Murray, David; Tighe, Donal; Madden, Stephen F.; Mulligan, Anne-Marie; Keane, Conor O.; Brady, Hugh R.; Doran, Peter P.; MacMathuna, Padraic

    2006-01-01

    We have identified novel colorectal cancer-associated genes using NCBI's UNIGENE cDNA libraries. Colon cancer libraries were examined using Digital Differential Display and disease-associated genes were selected. Among these were ETV4 and MYEOV, novel colorectal cancer-associated genes. Samples of matched normal and neoplastic colon were obtained from human subjects and gene expression was quantified using real-time PCR. ETV4 gene expression was significantly increased in colonic neoplasia in comparison to matched normal colonic tissue (p < 0.05). Myeov expression was also increased in colon neoplasia in comparison to matched normal tissue. The effect of siRNA-mediated knockdown of ETV4 and Myeov on cell proliferation and invasion was assessed. ETV4 knockdown resulted in a 90% decrease in cell proliferation (p < 0.05) and a 67% decrease in cell invasion. Myeov knockdown resulted in a 48% decrease in cell proliferation (p < 0.05) and a 36% decrease in cell invasion. These data suggest that ETV4 and Myeov may provide novel targets for therapeutic intervention

  15. The prognostic significance of extramural deposits and extracapsular lymph node invasion in colon cancer.

    LENUS (Irish Health Repository)

    Al Sahaf, Osama

    2011-08-01

    The status of resected lymph nodes in colon cancer determines prognosis and further treatment. The American Joint Committee on Cancer staging system has designated extramural nodules as nonnodal disease and classified them as extensions of the T category in the sixth edition and as site-specific tumor deposits in the seventh edition. Extracapsular lymph node extension is an established poor prognostic indicator in many cancers. Its significance in colon cancer has not been extensively investigated.

  16. Colon cancer in Luxembourg: a national population-based data report, 1988–1998

    International Nuclear Information System (INIS)

    Scheiden, René; Pescatore, Paul; Wagener, Yolande; Kieffer, Nelly; Capesius, Catherine

    2005-01-01

    Over the last two decades time trends in incidence rates of colorectal cancer, changes in the proportions of stage at diagnosis and changes in the anatomic sub-site distribution of colon cancers have been reported in some European countries. In order to determine a strategy for early detection of colon cancer in the Grand-Duchy of Luxembourg, all consecutive colon adenocarcinomas diagnosed during the period 1988–1998 at a nation-wide level were reviewed. The population-based data of the national Morphologic Tumour Registry report all new high-grade adenomas (i.e. high-grade intraepithelial adenomatous neoplasias) and all consecutive new invasive adenocarcinomas of the colon diagnosed in the central department of pathology. Attention has been focused on variations in incidence, stage, anatomical site distribution and survival rates. Rectal cancers were excluded. Over the study period, 254 new colonic high-grade adenomas and 1379 new invasive adenocarcinomas were found; the crude incidence rates of colon adenocarcinomas grew steadily by 30%. Comparing the two 5-year periods 1988–1992 and 1994–1998, the crude incidence rates of high-grade adenomas (stage 0) rose by 190%, that of stage I cases by 14.3%, stage II cases 12.9% and stage III cases 38.5%, whereas the crude incidence rates of stage IV cases decreased by 11.8%. The high-grade adenoma/adenocarcinoma ratio increased. The right-sided colonic adenocarcinomas in elderly patients (>69 years) increased by 76%. The observed survival rates correlated with tumour stages. The overall observed 5-year survival rate (stage I-IV) was 51 ± 3% (95% confidence interval). The increasing incidence rates of colon adenocarcinomas, the persistence of advanced tumour stages (stage III), the mortality rates which remain stable, and the changing trends in the age- and sub-site distribution underline the need for preventive measures at the age of 50 in asymptomatic patients to reduce mortality from colo(rectal) cancer

  17. Colon cancer in Luxembourg: a national population-based data report, 1988–1998

    Directory of Open Access Journals (Sweden)

    Wagener Yolande

    2005-05-01

    Full Text Available Abstract Background Over the last two decades time trends in incidence rates of colorectal cancer, changes in the proportions of stage at diagnosis and changes in the anatomic sub-site distribution of colon cancers have been reported in some European countries. In order to determine a strategy for early detection of colon cancer in the Grand-Duchy of Luxembourg, all consecutive colon adenocarcinomas diagnosed during the period 1988–1998 at a nation-wide level were reviewed. Methods The population-based data of the national Morphologic Tumour Registry report all new high-grade adenomas (i.e. high-grade intraepithelial adenomatous neoplasias and all consecutive new invasive adenocarcinomas of the colon diagnosed in the central department of pathology. Attention has been focused on variations in incidence, stage, anatomical site distribution and survival rates. Rectal cancers were excluded. Results Over the study period, 254 new colonic high-grade adenomas and 1379 new invasive adenocarcinomas were found; the crude incidence rates of colon adenocarcinomas grew steadily by 30%. Comparing the two 5-year periods 1988–1992 and 1994–1998, the crude incidence rates of high-grade adenomas (stage 0 rose by 190%, that of stage I cases by 14.3%, stage II cases 12.9% and stage III cases 38.5%, whereas the crude incidence rates of stage IV cases decreased by 11.8%. The high-grade adenoma/adenocarcinoma ratio increased. The right-sided colonic adenocarcinomas in elderly patients (>69 years increased by 76%. The observed survival rates correlated with tumour stages. The overall observed 5-year survival rate (stage I-IV was 51 ± 3% (95% confidence interval. Conclusion The increasing incidence rates of colon adenocarcinomas, the persistence of advanced tumour stages (stage III, the mortality rates which remain stable, and the changing trends in the age- and sub-site distribution underline the need for preventive measures at the age of 50 in asymptomatic

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

    Science.gov (United States)

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

    2012-06-01

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

  19. Perioperative functional activity of the alternative pathway of complement in patients with colonic cancer

    DEFF Research Database (Denmark)

    Baatrup, G; Zimmermann-Nielsen, E; Qvist, N

    1999-01-01

    OBJECTIVE: To investigate the functional capacity of the alternative pathway of complement in patients with cancer of the colon before, during, and after operation. DESIGN: Prospective study. SETTING: One university and two district hospitals, Denmark. SUBJECTS: 28 patients having elective...... or emergency operations for colonic cancer. INTERVENTIONS: Measurements of C3b fixing capacity of the alternative complement pathway in serum before, during, and after operation. MAIN OUTCOME MEASUREMENTS: The functional capacity of the alternative pathway of complement, and changes during operation. RESULTS......: The functional capacity of the alternative pathway in patients with cancer of the colon was above normal (p

  20. Comparison of Western and Asian Guidelines Concerning the Management of Colon Cancer.

    Science.gov (United States)

    Pellino, Gianluca; Warren, Oliver; Mills, Sarah; Rasheed, Shahnawaz; Tekkis, Paris P; Kontovounisios, Christos

    2018-02-01

    Guidelines are important to standardize treatments and optimize outcomes. Several societies have published authoritative guidelines for patients with colon cancer, and a certain degree of variation can be predicted. This study aims to compare Western and Asian guidelines for the management of colon cancer. A literature review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for studies published between 2010 and 2017 by the online resources from the official Web sites of the societies/panels. Sources included guidelines by European Society of Medical Oncology, the Japanese Society for Cancer of the Colon and Rectum, and the National Comprehensive Cancer Network. Only full-text studies and the latest guidelines dealing with colon cancer were included. Studies and guidelines were separately assessed by 2 authors, who independently identified discrepancies and areas for further research. These were discussed and agreed with by all the authors. The recommendations of the guidelines of each society were compared, seeking discrepancies and potential areas for improvement. Endoscopic techniques for the management of early colon cancer are discussed in detail in the Asian guidelines. Asian guidelines advocate extended (D3) lymphadenectomy on a routine basis in T3/T4 and in selected T2 patients, whereas such an approach is still under investigation in Western countries. Only US guidelines describe neoadjuvant chemotherapy and radiotherapy. All the guidelines recommend adjuvant treatment in selected stage II patients, but agreement exists that this is performed without solid evidence, because better outcomes are hypothesized based on studies including stage III or stage II/III patients. The role of cytoreductive surgery with intra-abdominal chemotherapy is dubious, and European guidelines only recommend it in the setting of trials. Asian guidelines endorse an aggressive surgical approach to peritoneal disease. Only US

  1. Therapeutic considerations in Dukes C colon cancer

    NARCIS (Netherlands)

    Bleeker, Willem Aldert

    2001-01-01

    Colon cancer is one of the main health issues in the western world. In the Netherlands more than 7000 patients are diagnosed yearly with this disease and half of them will die from it. Prognosis largely depends on tumor stage, which is estimated by radiological, clinical and histological

  2. Three surgical planes identified in laparoscopic complete mesocolic excision for right-sided colon cancer.

    Science.gov (United States)

    Zhu, Da-Jian; Chen, Xiao-Wu; OuYang, Man-Zhao; Lu, Yan

    2016-01-12

    Complete mesocolic excision provides a correct anatomical plane for colon cancer surgery. However, manifestation of the surgical plane during laparoscopic complete mesocolic excision versus in computed tomography images remains to be examined. Patients who underwent laparoscopic complete mesocolic excision for right-sided colon cancer underwent an abdominal computed tomography scan. The spatial relationship of the intraoperative surgical planes were examined, and then computed tomography reconstruction methods were applied. The resulting images were analyzed. In 44 right-sided colon cancer patients, the surgical plane for laparoscopic complete mesocolic excision was found to be composed of three surgical planes that were identified by computed tomography imaging with cross-sectional multiplanar reconstruction, maximum intensity projection, and volume reconstruction. For the operations performed, the mean bleeding volume was 73±32.3 ml and the mean number of harvested lymph nodes was 22±9.7. The follow-up period ranged from 6-40 months (mean 21.2), and only two patients had distant metastases. The laparoscopic complete mesocolic excision surgical plane for right-sided colon cancer is composed of three surgical planes. When these surgical planes were identified, laparoscopic complete mesocolic excision was a safe and effective procedure for the resection of colon cancer.

  3. MiR-34a inhibits colon cancer proliferation and metastasis by inhibiting platelet-derived growth factor receptor α.

    Science.gov (United States)

    Li, Chunyan; Wang, Yulin; Lu, Shuming; Zhang, Zhuqing; Meng, Hua; Liang, Lina; Zhang, Yan; Song, Bo

    2015-11-01

    The microRNA (miRNA), miR‑34a is significant in colon cancer progression. In the present study, the role of miR‑34a in colon cancer cell proliferation and metastasis was investigated. It was found that the expression of miR‑34a in colon cancer tissues and cell lines was lower when compared with that of normal tissues and cells. Further research demonstrated that miR‑34a inhibited cell proliferation, induced G1 phase arrest, and suppressed metastasis and epithelial mesenchymal transition in colon cancer cells. Bioinformatic prediction indicated that platelet‑derived growth factor receptor α (PDGFRA) was a potential target gene of miR‑34a and a luciferase assay identified that PDGFRA was a novel direct target gene of miR‑34a. In addition, assays of western blot analyses and quantitative reverse‑transcription polymerase chain reaction confirmed that miR‑34a decreased PDGFRA mRNA expression and protein levels in colon cancer cells. Assessment of cellular function indicated that miR‑34a inhibited colon cancer progression via PDGFRA. These findings demonstrate that miR‑34a may act as a negative regulator in colon cancer by targeting PDGFRA.

  4. CD44 regulates cell migration in human colon cancer cells via Lyn kinase and AKT phosphorylation.

    Science.gov (United States)

    Subramaniam, Venkateswaran; Vincent, Isabella R; Gardner, Helena; Chan, Emily; Dhamko, Helena; Jothy, Serge

    2007-10-01

    Colon cancer is among the leading causes of cancer death in North America. CD44, an adhesion and antiapoptotic molecule is overexpressed in colon cancer. Cofilin is involved in the directional motility of cells. In the present study, we looked at how CD44 might modulate cell migration in human colon cancer via cofilin. We used a human colon cancer cell line, HT29, which expresses CD44, HT29 where CD44 expression was knocked down by siRNA, SW620, a human colon cancer cell line which does not express CD44, stably transfected exons of CD44 in SW620 cells and the colon from CD44 knockout and wild-type mouse. Western blot analysis of siRNA CD44 lysates showed increased level of AKT phosphorylation and decreased level of cofilin expression. Similar results were also observed with SW620 cells and CD44 knockout mouse colon lysates. Experiments using the AKT phosphorylation inhibitor LY294002 indicate that AKT phosphorylation downregulates cofilin. Immunoprecipitation studies showed CD44 complex formation with Lyn, providing an essential link between CD44 and AKT phosphorylation. LY294002 also stabilized Lyn from phosphorylated AKT, suggesting an interaction between Lyn and AKT phosphorylation. Immunocytochemistry showed that cofilin and Lyn expression were downregulated in siRNA CD44 cells and CD44 knockout mouse colon. siRNA CD44 cells had significantly less migration compared to HT29 vector. Given the well-defined roles of CD44, phosphorylated AKT in apoptosis and cancer, these results indicate that CD44-induced cell migration is dependent on its complex formation with Lyn and its consequent regulation of AKT phosphorylation and cofilin expression.

  5. Self-expandable metal stents for obstructing colonic and extracolonic cancer

    DEFF Research Database (Denmark)

    van Hooft, Jeanin E; van Halsema, Emo E; Vanbiervliet, Geoffroy

    2014-01-01

    as a bridge to elective surgery is not recommended as a standard treatment of symptomatic left-sided malignant colonic obstruction (strong recommendation, high quality evidence). 3 For patients with potentially curable but obstructing left-sided colonic cancer, stent placement may be considered......, and Evaluation (GRADE) system was adopted to define the strength of recommendations and the quality of evidence. Main recommendations The following recommendations should only be applied after a thorough diagnostic evaluation including a contrast-enhanced computed tomography (CT) scan. 1 Prophylactic colonic...... stent placement is not recommended. Colonic stenting should be reserved for patients with clinical symptoms and imaging evidence of malignant large-bowel obstruction, without signs of perforation (strong recommendation, low quality evidence). 2 Colonic self-expandable metal stent (SEMS) placement...

  6. Transforming growth factor-β suppresses metastasis in a subset of human colon carcinoma cells

    International Nuclear Information System (INIS)

    Simms, Neka A K; Rajput, Ashwani; Sharratt, Elizabeth A; Ongchin, Melanie; Teggart, Carol A; Wang, Jing; Brattain, Michael G

    2012-01-01

    TGFβ signaling has typically been associated with suppression of tumor initiation while the role it plays in metastasis is generally associated with progression of malignancy. However, we present evidence here for an anti-metastatic role of TGFβ signaling. To test the importance of TGFβ signaling to cell survival and metastasis we compared human colon carcinoma cell lines that are either non-tumorigenic with TGFβ response (FET), or tumorigenic with TGFβ response (FETα) or tumorigenic with abrogated TGFβ response via introduction of dominant negative TGFβRII (FETα/DN) and their ability to metastasize. Metastatic competency was assessed by orthotopic transplantation. Metastatic colony formation was assessed histologically and by imaging. Abrogation of TGFβ signaling through introduction of a dominant negative TGFβ receptor II (TGFβRII) in non-metastatic FETα human colon cancer cells permits metastasis to distal organs, but importantly does not reduce invasive behavior at the primary site. Loss of TGFβ signaling in FETα-DN cells generated enhanced cell survival capabilities in response to cellular stress in vitro. We show that enhanced cellular survival is associated with increased AKT phosphorylation and cytoplasmic expression of inhibitor of apoptosis (IAP) family members (survivin and XIAP) that elicit a cytoprotective effect through inhibition of caspases in response to stress. To confirm that TGFβ signaling is a metastasis suppressor, we rescued TGFβ signaling in CBS metastatic colon cancer cells that had lost TGFβ receptor expression due to epigenetic repression. Restoration of TGFβ signaling resulted in the inhibition of metastatic colony formation in distal organs by these cells. These results indicate that TGFβ signaling has an important role in the suppression of metastatic potential in tumors that have already progressed to the stage of an invasive carcinoma. The observations presented here indicate a metastasis suppressor role for TGF

  7. Improved survival with early adjuvant chemotherapy after colonic resection for stage III colonic cancer

    DEFF Research Database (Denmark)

    Klein, Mads; Azaquoun, Najah; Jensen, Benny Vittrup

    2015-01-01

    . Data on patients with stage III colonic cancer operated between January 1, 2005 and August 31, 2012 were retrieved. Perioperative variables, surgical modality, and time to adjuvant therapy (8 weeks) were evaluated and Cox regression was performed to identify factors influencing survival...

  8. miR-409-3p sensitizes colon cancer cells to oxaliplatin by inhibiting Beclin-1-mediated autophagy.

    Science.gov (United States)

    Tan, Shifan; Shi, Huijuan; Ba, Mingchen; Lin, Shengqv; Tang, Hongsheng; Zeng, Xiaoqi; Zhang, Xiangliang

    2016-04-01

    The chemoresistance of colon cancer cells limits the efficacy of chemotherapy. miR-409-3p has been shown to be downregulated in various types of cancer. In the present study, we examined the role of miR-409-3p in colon cancer as well as the effects of miR‑409-3p on the sensitivity of colon cancer cells to oxaliplatin. The expression of miR-409 was significantly downregulated in the human colon cancer cell lines compared with the normal colon epithelial cells. Importantly, the miR-409-3p expression levels were lower in human colon cancer patient samples than in normal colon tissues. Moreover, we observed a negative correlation between the miR‑409-3p levels and resistance to oxaliplatin: the oxaliplatin-resistant colon cancer cells exhibited significantly downregulated miR‑409-3p levels, but higher autophagic activity than the oxaliplatin-sensitive cells. Using bioinformatics analysis, we predicted that miR‑409-3p miRNA binds to the key autophagy gene encoding Beclin-1. Our findings indicated that the overexpression of miR‑409-3p inhibited Beclin-1 expression and autophagic activity by binding to the 3'-untranslated region of Beclin-1 mRNA. In addition, the overexpression of miR‑409-3p enhanced the chemosensitivity of the oxaliplatin-sensitive and oxaliplatin-resistant colon cancer cells. The restoration of Beclin-1 abrogated these effects of miR‑409-3p. In a xenograft model using nude mice, we examined the effects of miR‑409-3p on tumor growth during chemotherapy. miR‑409-3p overexpression sensitized the tumor to chemotherapy, while inhibiting chemotherapy-induced autophagy in a manner dependent on Beclin-1. The findings of our study suggest that miR-409-3p is capable of enhancing the chemosensitivity of colon cancer cells by inhibiting Beclin-1-mediated autophagy.

  9. Colon cancer metastasis to the mandibular gingiva with partial occult squamous differentiation: A case report and literature review.

    Science.gov (United States)

    Ren, Quan-Guang; Huang, Tao; Yang, Sheng-Li; Hu, Jian-Li

    2017-02-01

    Metastasis is the primary cause of death among patients with colon cancer. However, the number of available studies regarding oral cavity metastases from colon cancer is currently limited. We herein report an unusual case of a 60-year-old male patient who developed an oral cavity metastasis from colon cancer. A total of 12 clinical case studies reporting colon cancer metastases to the mandibular gingival region were also reviewed, with the aim to elucidate the clinical and pathological characteristics of this disease entity in order to improve clinical diagnosis and treatment. It was demonstrated that patients with oral cavity metastases from colon cancer were predominantly in the sixth or seventh decades of life. The mandible was the main site of metastatic tumors to the oral cavity, while the occurrence of gingival metastases was comparatively rare. Moreover, the diagnoses of an oral metastatic tumor and primary colon cancer were often synchronous and were frequently accompanied with metastases to other organs. Several key aspects were suggested that should be accounted for when diagnosing colon cancer patients, including focusing attention to oral symptoms when examining cancer patients, utilizing a multidisciplinary approach for differential diagnosis and utilizing postoperative pathological examination to accurately diagnose the type of tumor and optimize the efficacy of treatment.

  10. Nonelective colon cancer resections in elderly patients: results from the dutch surgical colorectal audit

    NARCIS (Netherlands)

    Kolfschoten, N. E.; Wouters, M. W. J. M.; Gooiker, G. A.; Eddes, E. H.; Kievit, J.; Tollenaar, R. A. E. M.; Marang-van de Mheen, P. J.; Bemelman, W. A.; Busch, O. R. C.; van Dam, R. M.; van der Harst, E.; Jansen-Landheer, M. L. E. A.; Karsten, Th M.; van Krieken, J. H. J. M.; Kuijpers, W. G. T.; Lemmens, V. E.; Manusama, E. R.; Meijerink, W. J. H. J.; Rutten, H. J. T.; van de Velde, C. J. H.; Wiggers, T.

    2012-01-01

    The aim of the study was to assess which factors contribute to postoperative mortality, especially in elderly patients who undergo emergency colon cancer resections, using a nationwide population-based database. 6,161 patients (1,172 nonelective) who underwent a colon cancer resection in 2010 in the

  11. Up-regulation of CHAF1A, a poor prognostic factor, facilitates cell proliferation of colon cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Zehua; Cui, Feifei; Yu, Fudong; Peng, Xiao; Jiang, Tao; Chen, Dawei [Department of General Surgery, Shanghai Jiaotong University Affiliated First People’s Hospital, 85 Wujin Road, Shanghai 200080 (China); Lu, Su [Department of Pathology, Shanghai Jiaotong University Affiliated First People’s Hospital, 85 Wujin Road, Shanghai 200080 (China); Tang, Huamei, E-mail: tanghuamei@gmail.com [Department of Pathology, Shanghai Jiaotong University Affiliated First People’s Hospital, 85 Wujin Road, Shanghai 200080 (China); Peng, Zhihai, E-mail: zhihai.peng@hotmail.com [Department of General Surgery, Shanghai Jiaotong University Affiliated First People’s Hospital, 85 Wujin Road, Shanghai 200080 (China)

    2014-06-27

    Highlights: • We identified that CHAF1A was up-regulated in colon tumor mucosa in TMA. • The expression pattern of CHAF1A was validated with qPCR and western-blot. • CHAF1A overexpression is an independent indicator for poor colon cancer survival. • CHAF1A facilitates cell proliferation of colon cancer both in vitro and in vivo. - Abstract: Deregulation of chromatin assembly factor 1, p150 subunit A (CHAF1A) has recently been reported to be involved in the development of some cancer types. In this study, we identified that the frequency of positive CHAF1A staining in primary tumor mucosa (45.8%, 93 of 203 samples) was significantly elevated compared to that in paired normal mucosa (18.7%, 38 of 203 samples). The increased expression was strongly associated with cancer stage, tumor invasion, and histological grade. The five-year survival rate of patients with CHAF1A-positive tumors was remarkably lower than that of patients with CHAF1A-negative tumors. Colon cancer cells with CHAF1A knockdown exhibited decreased cell growth index, reduction in colony formation ability, elevated cell apoptosis rate as well as impaired colon tumorigenicity in nude mice. Hence, CHAF1A upregulation functions as a poor prognostic indicator of colon cancer, potentially contributing to its progression by mediating cancer cell proliferation.

  12. Up-regulation of CHAF1A, a poor prognostic factor, facilitates cell proliferation of colon cancer

    International Nuclear Information System (INIS)

    Wu, Zehua; Cui, Feifei; Yu, Fudong; Peng, Xiao; Jiang, Tao; Chen, Dawei; Lu, Su; Tang, Huamei; Peng, Zhihai

    2014-01-01

    Highlights: • We identified that CHAF1A was up-regulated in colon tumor mucosa in TMA. • The expression pattern of CHAF1A was validated with qPCR and western-blot. • CHAF1A overexpression is an independent indicator for poor colon cancer survival. • CHAF1A facilitates cell proliferation of colon cancer both in vitro and in vivo. - Abstract: Deregulation of chromatin assembly factor 1, p150 subunit A (CHAF1A) has recently been reported to be involved in the development of some cancer types. In this study, we identified that the frequency of positive CHAF1A staining in primary tumor mucosa (45.8%, 93 of 203 samples) was significantly elevated compared to that in paired normal mucosa (18.7%, 38 of 203 samples). The increased expression was strongly associated with cancer stage, tumor invasion, and histological grade. The five-year survival rate of patients with CHAF1A-positive tumors was remarkably lower than that of patients with CHAF1A-negative tumors. Colon cancer cells with CHAF1A knockdown exhibited decreased cell growth index, reduction in colony formation ability, elevated cell apoptosis rate as well as impaired colon tumorigenicity in nude mice. Hence, CHAF1A upregulation functions as a poor prognostic indicator of colon cancer, potentially contributing to its progression by mediating cancer cell proliferation

  13. Associations between red meat and risks for colon and rectal cancer depend on the type of red meat consumed.

    Science.gov (United States)

    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.

  14. 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

    Science.gov (United States)

    2017-06-26

    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

  15. Tussilagone suppresses colon cancer cell proliferation by promoting the degradation of β-catenin

    International Nuclear Information System (INIS)

    Li, Hua; Lee, Hwa Jin; Ahn, Yeon Hwa; Kwon, Hye Jin; Jang, Chang-Young; Kim, Woo-Young; Ryu, Jae-Ha

    2014-01-01

    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

  16. Laparoscopic resection of transverse colon cancer at splenic flexure: technical aspects and results.

    Science.gov (United States)

    Okuda, Junji; Yamamoto, Masashi; Tanaka, Keitaro; Masubuchi, Shinsuke; Uchiyama, Kazuhisa

    2016-03-01

    Laparoscopic resection of transverse colon cancer at splenic flexure is technical demanding and its efficacy remains controversial. The aim of this study was to investigate its technical aspects such as pitfalls and overcoming them, and to demonstrate the short-term and oncologic long-term outcomes. To overcome the difficulty in laparoscopic resection of transverse colon cancer at splenic flexure, we recognized the following technical tips as essential. First of all, we have to precisely identify major vessels variations feeding tumor. Secondary, anatomical dissection of mesocolon through medial approach is indispensible. Third, safe takedown of splenic flexure to fully mobilization of left hemicolon is mandatory. This cohort study analyzed 95 patients with stage II (43) and III (52) underwent resection of transverse colon cancer at splenic flexure. 61 laparoscopic surgeries (LAC) and 34 conventional open surgeries (OC) from December 1996 to December 2009 were evaluated. Short-term and oncologic long-term outcomes were recorded. Operative time was longer in LAC. However, blood loss was less, recovery of bowel function and hospital stay were shorter in LAC. There was no conversion in LAC and no significant difference in the postoperative complications. Regarding oncologic long-term outcomes, there were no significant differences between OC and LAC. Laparoscopic resection of transverse colon cancer at splenic flexure resulted in acceptable short-term and oncologic long-term outcomes. Once technical tips acquired, laparoscopic resection of transverse colon cancer at splenic flexure could be feasible as minimally invasive surgery.

  17. Tussilagone suppresses colon cancer cell proliferation by promoting the degradation of β-catenin

    Energy Technology Data Exchange (ETDEWEB)

    Li, Hua [College of Pharmacy and Research Center for Cell Fate Control, Sookmyung Women’s University, 52 Hyochangwon-Gil, Yongsan-Gu, Seoul 140-742 (Korea, Republic of); Lee, Hwa Jin [Department of Natural Medicine Resources, Semyung University, 65 Semyung-ro, Jecheon, Chungbuk 390-711 (Korea, Republic of); Ahn, Yeon Hwa; Kwon, Hye Jin; Jang, Chang-Young; Kim, Woo-Young [College of Pharmacy and Research Center for Cell Fate Control, Sookmyung Women’s University, 52 Hyochangwon-Gil, Yongsan-Gu, Seoul 140-742 (Korea, Republic of); Ryu, Jae-Ha, E-mail: ryuha@sookmyung.ac.kr [College of Pharmacy and Research Center for Cell Fate Control, Sookmyung Women’s University, 52 Hyochangwon-Gil, Yongsan-Gu, Seoul 140-742 (Korea, Republic of)

    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.

  18. Decreased risk of surgery for small bowel obstruction after laparoscopic colon cancer surgery compared with open surgery

    DEFF Research Database (Denmark)

    Jensen, Kristian Kiim; Andersen, Peter; Erichsen, Rune

    2016-01-01

    cancer resection. METHODS: This was a nationwide cohort study of patients undergoing elective colonic cancer resection with primary anastomosis in Denmark between 2001 and 2008. All included patients were operated with curative intent. Patients were identified in the Danish Colorectal Cancer Group....... The HR for mortality after colonic resection was 2.54 (CI 1.91 to 3.38, P ... surgery. Further, subsequent SBO surgery was associated with increased mortality after colonic cancer resection....

  19. Translating tumor biology into personalized treatment planning: analytical performance characteristics of the Oncotype DX? Colon Cancer Assay

    OpenAIRE

    Clark-Langone, Kim M; Sangli, Chithra; Krishnakumar, Jayadevi; Watson, Drew

    2010-01-01

    Abstract Background The Oncotype DX® Colon Cancer Assay is a new diagnostic test for determining the likelihood of recurrence in stage II colon cancer patients after surgical resection using fixed paraffin embedded (FPE) primary colon tumor tissue. Like the Oncotype DX Breast Cancer Assay, this is a high complexity, multi-analyte, reverse transcription (RT) polymerase chain reaction (PCR) assay that measures the expression levels of specific cancer-related genes. By capturing the biology unde...

  20. Incidence of venous thromboembolic events in enhanced recovery after surgery for colon cancer

    DEFF Research Database (Denmark)

    Vendler, M M I; Haidari, T A; Waage, J E

    2017-01-01

    AIM: Both the Danish and the National Institute of Clinical Excellence (NICE) guidelines recommend prolonged thromboprophylaxis (PT) with low-molecular-weight heparin (LMWH) for 28 days postoperatively after elective surgery for colon cancer. The evidence relies on data from two randomized clinical...... trials (RCTs) that included not only colon cancers but also other abdominal cancers or benign colorectal diseases. Neither of those studies investigated the risk of venous thromboembolism (VTE) under enhanced recovery after surgery (ERAS). We aim to describe the risk of VTE and estimate the cost...... of preventing one case of VTE by PT under ERAS. METHOD: This was a retrospective study of 2230 patients undergoing elective surgery for colon cancer Stage I-III in the Capital Region of Denmark, 1 June 2008 to 31 December 2013. Patients who were discharged on postoperative day 28 or later, died during admission...

  1. Pathogenesis of morbidity after fast-track laparoscopic colonic cancer surgery

    DEFF Research Database (Denmark)

    Stottmeier, S; Harling, H; Wille-Jørgensen, P

    2011-01-01

    AIM: Analysis of the nature and time course of early complications after laparoscopic colonic surgery is required to allow rational strategies for their prevention and management. METHOD: One hundred and four consecutive patients who underwent elective fast-track laparoscopic colonic cancer surgery...... occurred in 14 patients, of which four were preceded by medical complications. Three patients had only medical complications. Median length of stay was 3 days (range 1-44). CONCLUSION: Further improvement of outcomes after fast-track laparoscopic colonic surgery might be obtained by improved surgical...

  2. Use of capecitabine in management of early colon cancer

    Directory of Open Access Journals (Sweden)

    Cassidy J

    2011-08-01

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

  3. Differential regulation of EGFR-MAPK signaling by deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) in colon cancer.

    Science.gov (United States)

    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.

  4. [Postoperative intraperitoneal complications in colon cancer surgery].

    Science.gov (United States)

    Erokhina, E A; Topuzov, É G; Topuzov, É É

    2014-01-01

    The authors studied the clinical characteristics and terms of the development of postoperative intraperitoneal complications in patients undergoing colon cancer surgery. It was stated, that the diversity of clinical data depended on complication characteristics. Results of investigation allowed defining of the most dangerous terms of intraperitoneal complications and risk factors.

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

    Science.gov (United States)

    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.

  6. γδ T cells as a potential tool in colon cancer immunotherapy.

    Science.gov (United States)

    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.

  7. Colon cancer controls versus population controls in case-control studies of occupational risk factors

    DEFF Research Database (Denmark)

    Kaerlev, Linda; Lynge, Elsebeth; Sabroe, Svend

    2004-01-01

    are interchangeable with the experience for population controls. Patient controls may even be preferable from population controls under certain conditions. In this study we examine if colon cancer patients can serve as surrogates for proper population controls in case-control studies of occupational risk factors...... about occupational, medical and life style conditions. RESULTS: No statistical significant difference for educational level, medical history or smoking status was seen between the two control groups. There was evidence of a higher alcohol intake, less frequent work as a farmer and less exposure...... to pesticides among colon cancer controls. CONCLUSIONS: Use of colon cancer controls may provide valid exposure estimates in studies of many occupational risk factors for cancer, but not for studies on exposure related to farming....

  8. Overtreatment of young adults with colon cancer: more intense treatments with unmatched survival gains.

    Science.gov (United States)

    Kneuertz, Peter J; Chang, George J; Hu, Chung-Yuan; Rodriguez-Bigas, Miguel A; Eng, Cathy; Vilar, Eduardo; Skibber, John M; Feig, Barry W; Cormier, Janice N; You, Y Nancy

    2015-05-01

    Colon cancer is increasing among adults younger than 50 years. However, the prognosis of young-onset colon cancer remains poorly defined given significant age-related demographic, disease, and treatment differences. To define stage-specific treatments and prognosis of colon cancer diagnosed in young adults (ages 18-49 years) vs older adults (ages 65-75 years) outside of the clinical trial setting while accounting for real-world age-related variations in patient, tumor, and treatment factors. A nationwide cohort study was conducted among US hospitals accredited by the American College of Surgeons Commission on Cancer. Participants were 13 102 patients diagnosed as having young-onset colon adenocarcinoma aged 18 to 49 years and 37 007 patients diagnosed as having later-onset colon adenocarcinoma aged 65 to 75 years treated between January 1, 2003, and December 31, 2005, and reported to the National Cancer Data Base. Patients who underwent surgical resection and postoperative systemic chemotherapy of curative intent. The primary end point was stage-specific relative survival, an objective measure of survival among patients with cancer, adjusting for baseline mortality rates and independent of the data on cause of death. The secondary end point was stage-specific likelihood of receiving postoperative systemic chemotherapy. Most young-onset colon cancer was initially seen at advanced stages (61.8% had stage III or IV). After adjusting for patient-related and tumor-related factors, young patients were more likely to receive systemic chemotherapy, particularly multiagent regimens, at all stages relative to those with later-onset disease. These odds ratios were 2.88 (95% CI, 2.21-3.77) for stage I, 3.93 (95% CI, 3.58-4.31) for stage II, 2.42 (95% CI, 2.18-2.68) for stage III, and 2.74 (95% CI, 2.44-3.07) for stage IV. The significantly more intense treatments received by younger patients were unmatched by any survival gain, which was nil for stage II (relative risk, 0

  9. Epigenetic repression of ROR2 has a Wnt-mediated, pro-tumourigenic role in colon cancer

    Directory of Open Access Journals (Sweden)

    López-Otín Carlos

    2010-06-01

    Full Text Available Abstract Background Wnt factors control cell differentiation through semi-independent molecular cascades known as the β-catenin-dependent (canonical and -independent (non-canonical Wnt signalling pathways. Genetic and epigenetic alteration of components of the canonical Wnt signalling pathway is one of the primary mechanisms underlying colon cancer. Despite increasing evidence of the role of the non-canonical pathways in tumourigenesis, however, the underlying molecular mechanisms are poorly understood. Results Here we report that the receptor tyrosine kinase-like orphan receptor 2 (ROR2, a transmembrane receptor for Wnt factors that activates non-canonical pathways, is frequently repressed by aberrant promoter hypermethylation in human colon cancer cell lines and primary tumours. By restoring ROR2 activity in colon cancer cells harbouring ROR2 promoter hypermethylation, we show that the role of ROR2 in colon cancer cells is mediated, at least in part, by canonical Wnt and that its epigenetic-dependent loss can be pro-tumourigenic. Conclusions Our data show the importance of epigenetic alterations of ROR2 in colon cancer, highlighting the close interconnection between canonical and non-canonical Wnt signalling pathways in this type of tumour.

  10. Survival benefit associated with adjuvant androgen deprivation therapy combined with radiotherapy for high- and low-risk patients with nonmetastatic prostate cancer

    International Nuclear Information System (INIS)

    Zeliadt, Steven B.; Potosky, Arnold L.; Penson, David F.; Etzioni, Ruth

    2006-01-01

    Background: The use of adjuvant androgen deprivation therapy (ADT) combined with radiotherapy has become common in low-risk patients, although clinical trials have focused primarily on high-risk patients. This study examines the effectiveness of adjuvant ADT combined with radiotherapy for a wide range of patients treated in the 1990s. Methods and Materials: Prostate cancer survival was examined in a population based cohort of 31,643 patients aged 65 to 85 years who were diagnosed with nonmetastatic prostate cancer and treated with external beam radiotherapy and/or brachytherapy. Instrumental variable analysis methods were used to control for selection bias. Results: Patients with stage T3/T4 disease who received adjuvant ADT experienced improved 5-year and 8-year survival. No survival advantage was observed for men with T1/T2 disease during this interval. Conclusion: High-risk patients who receive primary radiotherapy have benefited from adjuvant ADT, whereas low-risk patients with disease confined to the prostate have not yet benefited from adjuvant therapy within the first 8 years after treatment. These findings are consistent with practice guidelines, which recommend adjuvant ADT for patients with high-risk disease

  11. Deficient Pms2, ERCC1, Ku86, CcOI in field defects during progression to colon cancer.

    Science.gov (United States)

    Nguyen, Huy; Loustaunau, Cristy; Facista, Alexander; Ramsey, Lois; Hassounah, Nadia; Taylor, Hilary; Krouse, Robert; Payne, Claire M; Tsikitis, V Liana; Goldschmid, Steve; Banerjee, Bhaskar; Perini, Rafael F; Bernstein, Carol

    2010-07-28

    In carcinogenesis, the "field defect" is recognized clinically because of the high propensity of survivors of certain cancers to develop other malignancies of the same tissue type, often in a nearby location. Such field defects have been indicated in colon cancer. The molecular abnormalities that are responsible for a field defect in the colon should be detectable at high frequency in the histologically normal tissue surrounding a colonic adenocarcinoma or surrounding an adenoma with advanced neoplasia (well on the way to a colon cancer), but at low frequency in the colonic mucosa from patients without colonic neoplasia. Using immunohistochemistry, entire crypts within 10 cm on each side of colonic adenocarcinomas or advanced colonic neoplasias were found to be frequently reduced or absent in expression for two DNA repair proteins, Pms2 and/or ERCC1. Pms2 is a dual role protein, active in DNA mismatch repair as well as needed in apoptosis of cells with excess DNA damage. ERCC1 is active in DNA nucleotide excision repair. The reduced or absent expression of both ERCC1 and Pms2 would create cells with both increased ability to survive (apoptosis resistance) and increased level of mutability. The reduced or absent expression of both ERCC1 and Pms2 is likely an early step in progression to colon cancer. DNA repair gene Ku86 (active in DNA non-homologous end joining) and Cytochrome c Oxidase Subunit I (involved in apoptosis) had each been reported to be decreased in expression in mucosal areas close to colon cancers. However, immunohistochemical evaluation of their levels of expression showed only low to modest frequencies of crypts to be deficient in their expression in a field defect surrounding colon cancer or surrounding advanced colonic neoplasia. We show, here, our method of evaluation of crypts for expression of ERCC1, Pms2, Ku86 and CcOI. We show that frequency of entire crypts deficient for Pms2 and ERCC1 is often as great as 70% to 95% in 20 cm long areas

  12. The influence of hormone therapies on colon and rectal cancer

    DEFF Research Database (Denmark)

    Mørch, Lina Steinrud; Lidegaard, Øjvind; Keiding, Niels

    2016-01-01

    followed 1995–2009. Information on HT exposures was from the National Prescription Register and updated daily, while information on colon (n = 8377) and rectal cancers (n = 4742) were from the National Cancer Registry. Potential confounders were obtained from other national registers. Poisson regression...

  13. Effects of silk sericin on the proliferation and apoptosis of colon cancer cells

    Directory of Open Access Journals (Sweden)

    Waraporn Kaewkorn

    2012-01-01

    Full Text Available 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.

  14. Optical density measurements on the examination of colon cancer tissues

    International Nuclear Information System (INIS)

    Touati, E.; Ajaal, T.; Hamassi, A.

    2015-01-01

    Automated quantitative image analysis can aid in cancer diagnosis and, in general, mange medical treatments managements and improve routine medical diagnosis. Early diagnosis can make big difference between life and death. Microscopic images from two tissue types forty-four normal and fifty-eight cancers, was evaluated based on their ability to identify abnormalities in colon images. Optical density approach is applied to extract parameters that exhibit cancer behavior on colon tissues images. Using statistical toolbox, a significant result of (p<0.0001) for the mean and the variance of the optical density parameter were detected, and only (p<0.001) for skewness optical density. based on linear discrimination method, the obtained result shows 905 accuracy for both sensitivity and specificity, and with an overall accuracy of 90% (author)

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

    Directory of Open Access Journals (Sweden)

    Huang Po-Yen

    2017-01-01

    Full Text Available 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.

  16. Vitamin D receptor gene polymorphisms, dietary promotion of insulin resistance, and colon and rectal cancer.

    Science.gov (United States)

    Murtaugh, Maureen A; Sweeney, Carol; Ma, Khe-Ni; Potter, John D; Caan, Bette J; Wolff, Roger K; Slattery, Martha L

    2006-01-01

    Modifiable risk factors in colorectal cancer etiology and their interactions with genetic susceptibility are of particular interest. Functional vitamin D receptor (VDR) gene polymorphisms may influence carcinogenesis through modification of cell growth, protection from oxidative stress, cell-cell matrix effects, or insulin and insulin-like growth factor pathways. We investigated interactions between foods (dairy products, red and processed meat, and whole and refined grains) and dietary patterns (sucrose-to-fiber ratio and glycemic index) associated with insulin resistance with the FokI polymorphism of the VDR gene and colon and rectal cancer risk. Data (diet, anthropometrics, and lifestyle) and DNA came from case-control studies of colon (1,698 cases and 1,861 controls) and rectal cancer (752 cases and 960 controls) in northern California, Utah, and the Twin Cities metropolitan area, Minnesota (colon cancer study only). Unconditional logistic regression models were adjusted for smoking, race, sex, age, body mass index, physical activity, energy intake, dietary fiber, and calcium. The lowest colon cancer risk was observed with the Ff/ff FokI genotypes and a low sucrose-to-fiber ratio. Rectal cancer risk decreased with greater consumption of dairy products and increased with red or processed meat consumption and the FF genotype. Modifiable dietary risk factors may be differentially important among individuals by VDR genotype and may act through the insulin pathway to affect colon cancer risk and through fat, calcium, or other means to influence rectal cancer risk.

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

    OpenAIRE

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

    1995-01-01

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

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

    Science.gov (United States)

    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. © The Author(s) 2015.

  19. Protective, elective lung irradiation in non-metastatic Ewing's sarcoma

    International Nuclear Information System (INIS)

    Marinova, L.; Hristozova, I.; Mihaylova, I.; Perenovska, P.

    2015-01-01

    Ewing's sarcoma in childhood is a disease from family of the peripheral primitive neuroectodermal tumours. For a period of 16 y (1984-2000), 34 children with Ewing's sarcoma were treated and followed in our department. Twenty-seven of these patients were without distant metastases. Complex treatment was applied to all these patients-chemotherapy VACA (vincristine, actinomycin D, cyclophosphamide, adriamycin), local radiotherapy to a total dose of 50-56 Gy ± surgery. After, a local tumour control was achieved in 11 children with non-metastatic Ewing's sarcoma, elective whole lung irradiation to a total dose of 12-15 Gy was applied. Our experience in these 11 patients with non-metastatic Ewing's sarcoma, in whom elective lung irradiation was applied, showed significant reduction in the lung metastases, improved free of disease survival and overall survival. The achieved good treatment results necessitate extending this treatment approach through defining the risk groups of patients, suitable for elective lung radiotherapy combined with chemotherapy in non-metastatic Ewing's sarcoma. (authors)

  20. Clinical significance of adiponectin expression in colon cancer patients

    Directory of Open Access Journals (Sweden)

    Mustafa Canhoroz

    2014-01-01

    Conclusion: Adiponectin, which is secreted by adipose tissue, may have a role in the development and progression of cancer via its pro-apoptotic and/or anti-proliferative effects. Adiponectin expression in tumor tissues is likely to have a negative effect on disease - free survival in patients with stage II/III colon cancer; however, no statistically significant effect was demonstrated.

  1. Functional Status After Colon Cancer Surgery In Elder Nursing Home Residents

    Science.gov (United States)

    Finlayson, Emily; Zhao, Shoujun; Boscardin, W. John; Fries, Brant E.; Landefeld, C. Seth; Dudley, R. Adams

    2015-01-01

    Objectives To determine functional status and mortality rates after colon cancer surgery in older nursing home residents. Design Retrospective cohort study. Setting and Participants 6822 nursing home residents age 65 and older who underwent surgery for colon cancer in the United States between 1999 and 2005. Measurements Changes in functional status were assessed before and after surgery using the Minimum Data Set-Activities of Daily Living (MDS-ADL) summary scale, a 28-point scale in which score increases as functional dependence increases. Methods Using the Medicare Inpatient File and the Minimum Data Set for Nursing Homes, we identified the 6822 nursing home residents age 65 and older who underwent surgery for colon cancer. We used regression techniques to identify patient characteristics associated with mortality and functional decline at 1 year after surgery. Results On average, residents who underwent colectomy experienced a 3.9 point worsening in MDS-ADL score at one year. One year after surgery, the rates of mortality and sustained functional decline were 53% and 24%, respectively. In multivariate analysis, older age (age 80+ v. age 65–69, adjusted relative risk (ARR 1.53), 95%CI 1.15–2.04, pppp<0.0001) were associated with functional decline at one year. Conclusion Mortality and sustained functional decline are very common after colon cancer surgery in nursing home residents. Initiatives aimed at improving surgical outcomes are needed in this vulnerable population. PMID:22428583

  2. A comparison of laparoscopic and open D3 lymphadenectomy for transverse colon cancer.

    Science.gov (United States)

    Kwak, Han Deok; Ju, Jae Kyun; Lee, Soo Young; Kim, Chang Hyun; Kim, Young Jin; Kim, Hyeong Rok

    2017-12-01

    The type of surgery or surgical approach for transverse colon cancer treatment largely depends on the tumor location or surgeon's preference. However, extensive lymphadenectomy appears to improve the long-term outcomes of locally advanced colon cancers. This study was designed to compare the short- and long-term outcomes after surgery via the laparoscopic or open approach with radical D3 lymph node dissection in patients with stage II and III transverse colon cancer. Patients were treated for stage II and III transverse colon cancer between May 2006 and December 2014. This retrospective study evaluated data collected prospectively at a tertiary teaching hospital. Radical D3 lymphadenectomy included the principal middle colic artery nodes. The study included 144 patients among whom 118 (81.9%) underwent laparoscopic surgery. Significantly more patients in the laparoscopic group underwent extended right hemicolectomy compared with the open group (90.7 vs. 65.4%, p = 0.005). The operative time was longer in the laparoscopic group (151.3 vs. 131.2 min, p = 0.021), and the open group had a greater estimated blood loss volume (160.8 vs. 289.3 ml, p = 0.011). Although the groups differed in terms of tumor size (5.8 vs 7.9 cm, p = 0.007), other pathologic outcomes did not differ. The groups did not differ regarding postoperative parameters or disease-free, overall, and cancer-specific survivals. Despite differences in surgical methods and related factors, no long-term differences in outcomes were observed between laparoscopic and open approaches to radical D3 lymphadenectomy in patients with stage II and III transverse colon cancer.

  3. Outcome for stage II and III rectal and colon cancer equally good after treatment improvement over three decades.

    Science.gov (United States)

    Fischer, Joern; Joern, Fischer; Hellmich, Gunter; Gunter, Hellmich; Jackisch, Thomas; Thomas, Jackisch; Puffer, Erik; Erik, Puffer; Zimmer, Jörg; Jörg, Zimmer; Bleyl, Dorothea; Dorothea, Bleyl; Kittner, Thomas; Thomas, Kittner; Witzigmann, Helmut; Helmut, Witzigmann; Stelzner, Sigmar; Sigmar, Stelzner

    2015-06-01

    This study aimed to investigate the outcome for stage II and III rectal cancer patients compared to stage II and III colonic cancer patients with regard to 5-year cause-specific survival (CSS), overall survival, and local and combined recurrence rates over time. This prospective cohort study identified 3,355 consecutive patients with adenocarcinoma of the colon or rectum and treated in our colorectal unit between 1981 and 2011, for investigation. The study was restricted to International Union Against Cancer (UICC) stages II and III. Postoperative mortality and histological incomplete resection were excluded, which left 995 patients with colonic cancer and 726 patients with rectal cancer for further analysis. Five-year CSS rates improved for colonic cancer from 65.0% for patients treated between 1981 and 1986 to 88.1% for patients treated between 2007 and 2011. For rectal cancer patients, the respective 5-year CSS rates improved from 53.4% in the first observation period to 89.8% in the second one. The local recurrence rate for rectal cancer dropped from 34.2% in the years 1981-1986 to 2.1% in the years 2007-2011. In the last decade of observation, prognosis for rectal cancer was equal to that for colon cancer (CSS 88.6 vs. 86.7%, p = 0.409). Survival of patients with colon and rectal cancer has continued to improve over the last three decades. After major changes in treatment strategy including introduction of total mesorectal excision and neoadjuvant (radio)chemotherapy, prognosis for stage II and III rectal cancer is at least as good as for stage II and III colonic cancer.

  4. Isolated metastasis of colon cancer to the scapula: is surgical resection warranted?

    Directory of Open Access Journals (Sweden)

    Onesti Jill K

    2011-10-01

    Full Text Available Abstract Background Distant metastases from colon cancer spread most frequently to the liver and the lung. Risk factors include positive lymph nodes and high grade tumors. Isolated metastases to the appendicular skeleton are very rare, particularly in the absence of identifiable risk factors. Case report The patient was a 55 year old male with no previous personal or family history of colon cancer. Routine screening revealed a sigmoid adenocarcinoma. He underwent resection with primary anastomosis and was found to have Stage IIA colon cancer. He declined chemotherapy as part of a clinical trial, and eight months later was found to have an isolated metastasis in his right scapula. This was treated medically, but grew to 12 × 15 cm. The patient underwent a curative forequarter amputation and is now more than four years from his original colon surgery. Discussion Stage IIA colon cancers are associated with a high five year survival rate, and chemotherapy is not automatically given. If metastases occur, they are likely to arise from local recurrence or follow lymphatic dissemination to the liver or lungs. Isolated skeletal metastases are quite rare and are usually confined to the axial skeleton. To our knowledge, this is the first reported case of an isolated scapular metastasis in a patient with node negative disease. The decision to treat the recurrence with radiation and chemotherapy did not reduce the tumor, and a forequarter amputation was eventually required. Conclusion This case highlights the importance of adequately analyzing the stage of colon cancer and offering appropriate treatment. Equally important is the early involvement of a surgeon in discussing the timing of the treatment for recurrence. Perhaps if the patient had received chemotherapy or earlier resection, he could have been spared the forequarter amputation. The physician must also be aware of the remote possibility of an unusual presentation of metastasis in order to pursue

  5. Capecitabine treatment of HCT-15 colon cancer cells induces ...

    African Journals Online (AJOL)

    HCT-15 cells caused condensation of DNA and induced apoptosis in a concentration- ... Conclusion: Capecitabine treatment causes inhibition of colon cancer growth via the mitochondrial ... fluoropyrimidine aimed to selectively transfer 5-.

  6. Results of a phase I pilot clinical trial examining the effect of plant-derived resveratrol and grape powder on Wnt pathway target gene expression in colonic mucosa and colon cancer

    International Nuclear Information System (INIS)

    Nguyen, Anthony V; Martinez, Micaela; Stamos, Michael J; Moyer, Mary P; Planutis, Kestutis; Hope, Christopher; Holcombe, Randall F

    2009-01-01

    Resveratrol exhibits colon cancer prevention activity in animal models; it is purported to have this activity in humans and inhibit a key signaling pathway involved in colon cancer initiation, the Wnt pathway, in vitro. A phase I pilot study in patients with colon cancer was performed to evaluate the effects of a low dose of plant-derived resveratrol formulation and resveratrol-containing freeze-dried grape powder (GP) on Wnt signaling in the colon. Eight patients were enrolled and normal colonic mucosa and colon cancer tissue were evaluated by Wnt pathway-specific microarray and quantitative real-time polymerase chain reaction (qRT-PCR) pre- and post-exposure to resveratrol/GP. Based on the expression of a panel of Wnt target genes, resveratrol/GP did not inhibit the Wnt pathway in colon cancer but had significant (p < 0.03) activity in inhibiting Wnt target gene expression in normal colonic mucosa. The greatest effect on Wnt target gene expression was seen following ingestion of 80 g of GP per day (p < 0.001). These results were confirmed with qRT-PCR of cyclinD1 and axinII. The inhibitory effect of GP on Wnt signal throughput was confirmed in vitro with a normal colonic mucosa-derived cell line. These data suggest that GP, which contains low dosages of resveratrol in combination with other bioactive components, can inhibit the Wnt pathway in vivo and that this effect is confined to the normal colonic mucosa. Further study of dietary supplementation with resveratrol-containing foods such as whole grapes or GP as a potential colon cancer preventive strategy is warranted. NCT00256334

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

    Science.gov (United States)

    Zeng, Huawei; Lazarova, Darina L; Bordonaro, Michael

    2014-02-15

    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 modifies the host's metabolism in various ways. Elucidation of the mechanisms by which dietary fiber-dependent changes in gut microbiota enhance bile acid deconjugation, produce short chain fatty acids, and modulate inflammatory bioactive substances can lead to a better understanding of the beneficial role of dietary fiber. This article reviews the current knowledge concerning the mechanisms via which dietary fiber protects against colon cancer.

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

    African Journals Online (AJOL)

    effect. Although this association was mainly observed for colorectal cancer, associations were also found for pancreatic and prostate ... vegetarian diet in order to prevent colon cancer. ... cancers than males at 5.2% versus 4.8%.3 Stefan4 explains that .... Smoking. X-radiation, gamma radiation. Processed meat consumption.

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

    Science.gov (United States)

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

    2016-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Ostenfeld EB

    2011-07-01

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

  11. A mutational comparison of adult and adolescent and young adult (AYA) colon cancer.

    Science.gov (United States)

    Tricoli, James V; Boardman, Lisa A; Patidar, Rajesh; Sindiri, Sivasish; Jang, Jin S; Walsh, William D; McGregor, Paul M; Camalier, Corinne E; Mehaffey, Michele G; Furman, Wayne L; Bahrami, Armita; Williams, P Mickey; Lih, Chih-Jian; Conley, Barbara A; Khan, Javed

    2018-03-01

    It is possible that the relative lack of progress in treatment outcomes among adolescent and young adult (AYA) patients with cancer is caused by a difference in disease biology compared with the corresponding diseases in younger and older individuals. There is evidence that colon cancer is more aggressive and has a poorer prognosis in AYA patients than in older adult patients. To further understand the molecular basis for this difference, whole-exome sequencing was conducted on a cohort of 30 adult, 30 AYA, and 2 pediatric colon cancers. A statistically significant difference in mutational frequency was observed between AYA and adult samples in 43 genes, including ROBO1, MYC binding protein 2 (MYCBP2), breast cancer 2 (early onset) (BRCA2), MAP3K3, MCPH1, RASGRP3, PTCH1, RAD9B, CTNND1, ATM, NF1; KIT, PTEN, and FBXW7. Many of these mutations were nonsynonymous, missense, stop-gain, or frameshift mutations that were damaging. Next, RNA sequencing was performed on a subset of the samples to confirm the mutations identified by exome sequencing. This confirmation study verified the presence of a significantly greater frequency of damaging mutations in AYA compared with adult colon cancers for 5 of the 43 genes (MYCBP2, BRCA2, PHLPP1, TOPORS, and ATR). The current results provide the rationale for a more comprehensive study with a larger sample set and experimental validation of the functional impact of the identified variants along with their contribution to the biologic and clinical characteristics of AYA colon cancer. Cancer 2018;124:1070-82. © 2017 American Cancer Society. © 2017 American Cancer Society.

  12. Impact of Mesenchymal Stem Cell secreted PAI-1 on colon cancer cell migration and proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Hogan, Niamh M. [Discipline of Surgery, School of Medicine, National University of Ireland, Galway (Ireland); Joyce, Myles R. [Department of Colorectal Surgery, University College Hospital, Galway (Ireland); Murphy, J. Mary; Barry, Frank P.; O’Brien, Timothy [Regenerative Medicine Institute, National University of Ireland, Galway (Ireland); Kerin, Michael J. [Discipline of Surgery, School of Medicine, National University of Ireland, Galway (Ireland); Dwyer, Roisin M., E-mail: roisin.dwyer@nuigalway.ie [Discipline of Surgery, School of Medicine, National University of Ireland, Galway (Ireland)

    2013-06-14

    Highlights: •MSCs were directly co-cultured with colorectal cancer (CRC) cells on 3D scaffolds. •MSCs influence CRC protein/gene expression, proliferation and migration. •We report a significant functional role of MSC-secreted PAI-1 in colon cancer. -- Abstract: Mesenchymal Stem Cells are known to engraft and integrate into the architecture of colorectal tumours, with little known regarding their fate following engraftment. This study aimed to investigate mediators of Mesenchymal Stem Cell (MSC) and colon cancer cell (CCC) interactions. Mesenchymal Stem Cells and colon cancer cells (HT29 and HCT-116) were cultured individually or in co-culture on 3-dimensional scaffolds. Conditioned media containing all secreted factors was harvested at day 1, 3 and 7. Chemokine secretion and expression were analyzed by Chemi-array, ELISA (Macrophage migration inhibitory factor (MIF), plasminogen activator inhibitor type 1 (PAI-1)) and RQ-PCR. Colon cancer cell migration and proliferation in response to recombinant PAI-1, MSCs and MSCs + antibody to PAI-1 was analyzed using Transwell inserts and an MTS proliferation assay respectively. Chemi-array revealed secretion of a wide range of factors by each cell population, including PAI-1and MIF. ELISA analysis revealed Mesenchymal Stem Cells to secrete the highest levels of PAI-1 (MSC mean 10.6 ng/mL, CCC mean 1.01 ng/mL), while colon cancer cells were the principal source of MIF. MSC-secreted PAI-1 stimulated significant migration of both CCC lines, with an antibody to the chemokine shown to block this effect (67–88% blocking,). A cell-line dependant effect on CCC proliferation was shown for Mesenchymal Stem Cell-secreted PAI-1 with HCT-116 cells showing decreased proliferation at all concentrations, and HT29 cells showing increased proliferation in the presence of higher PAI-1 levels. This is the first study to identify PAI-1 as an important mediator of Mesenchymal Stem Cell/colon cancer cell interactions and highlights the

  13. Impact of Mesenchymal Stem Cell secreted PAI-1 on colon cancer cell migration and proliferation

    International Nuclear Information System (INIS)

    Hogan, Niamh M.; Joyce, Myles R.; Murphy, J. Mary; Barry, Frank P.; O’Brien, Timothy; Kerin, Michael J.; Dwyer, Roisin M.

    2013-01-01

    Highlights: •MSCs were directly co-cultured with colorectal cancer (CRC) cells on 3D scaffolds. •MSCs influence CRC protein/gene expression, proliferation and migration. •We report a significant functional role of MSC-secreted PAI-1 in colon cancer. -- Abstract: Mesenchymal Stem Cells are known to engraft and integrate into the architecture of colorectal tumours, with little known regarding their fate following engraftment. This study aimed to investigate mediators of Mesenchymal Stem Cell (MSC) and colon cancer cell (CCC) interactions. Mesenchymal Stem Cells and colon cancer cells (HT29 and HCT-116) were cultured individually or in co-culture on 3-dimensional scaffolds. Conditioned media containing all secreted factors was harvested at day 1, 3 and 7. Chemokine secretion and expression were analyzed by Chemi-array, ELISA (Macrophage migration inhibitory factor (MIF), plasminogen activator inhibitor type 1 (PAI-1)) and RQ-PCR. Colon cancer cell migration and proliferation in response to recombinant PAI-1, MSCs and MSCs + antibody to PAI-1 was analyzed using Transwell inserts and an MTS proliferation assay respectively. Chemi-array revealed secretion of a wide range of factors by each cell population, including PAI-1and MIF. ELISA analysis revealed Mesenchymal Stem Cells to secrete the highest levels of PAI-1 (MSC mean 10.6 ng/mL, CCC mean 1.01 ng/mL), while colon cancer cells were the principal source of MIF. MSC-secreted PAI-1 stimulated significant migration of both CCC lines, with an antibody to the chemokine shown to block this effect (67–88% blocking,). A cell-line dependant effect on CCC proliferation was shown for Mesenchymal Stem Cell-secreted PAI-1 with HCT-116 cells showing decreased proliferation at all concentrations, and HT29 cells showing increased proliferation in the presence of higher PAI-1 levels. This is the first study to identify PAI-1 as an important mediator of Mesenchymal Stem Cell/colon cancer cell interactions and highlights the

  14. Age at diagnosis in women with non-metastatic breast cancer: Is it related to prognosis?

    International Nuclear Information System (INIS)

    Alieldin, N.H.; Abo-Elazm, O.M.; Bilal, D.; Ibrahim, A.S.; Salem, S.E.; Gouda, E.; Elmongy, M.

    2014-01-01

    Objective: Primary objective was to verify whether breast cancer patients aged less than 40 years at diagnosis have poorer prognosis than older patients. Secondary to assess prognostic factors influencing disease free survival. Methods: 941 women were diagnosed with non-metastatic breast cancer at NCI, Cairo in 2003. Epidemiologic, clinico-pathological characteristics, treatment modalities and disease free survival were compared among the two age groups. Prognostic factors were evaluated for association with disease-free survival. Results: One hundred-eighty-one patients (19.2%) were younger than 40 years and 760 (80.8%) were older. Older women presented with higher rates of comorbidities and younger women presented with more hormone non-responsive tumors. Young women presented with larger tumors pT4 = 13.8% compared to 8.6% in older women, yet not significant. Young women were treated with more conservative surgery, more adjuvant chemotherapy and radiotherapy while older women with more radical mastectomies and more hormonal treatment. Recurrence rates were significantly higher among young women 44,2% compared to 34.5% in older women. Five year disease free survival in young women was 38.9% ± 4.6% compared to 48.6% ± 2.5% with adjusted hazard ratio of 1.22 95% Cl (0.91-1.64),p = 0.19. Multivariate analyses identified positive axillary lymph nodes (pN2-pN3), larger tumor size (pT3-pT4), hypertension, lobular carcinoma type and lack of adjuvant systemic treatment as independent factors associated with poor DFS. Conclusion: Young women were not found to have poorer prognosis, yet they presented with more ER negative tumors. Most of women presented with advanced stage and young women had higher recurrence rates.

  15. Gallic acid induced apoptotic events in HCT-15 colon cancer cells

    Science.gov (United States)

    Subramanian, Aruna Priyadharshni; Jaganathan, Saravana Kumar; Mandal, Mahitosh; Supriyanto, Eko; Muhamad, Ida Idayu

    2016-01-01

    AIM: To investigate the inhibitory action of diet-derived phenolic compound gallic acid (GA) against HCT-15 colon cancer cells. METHODS: The antiproliferative effect of GA against colon cancer cells was determined by performing thiazolyl blue tetrazolium bromide (MTT) assay. The colony forming ability of GA treated colon cancer cells was evaluated using the colony forming assay. The cell cycle changes induced by GA in HCT-15 cells were analyzed by propidium iodide staining. Levels of reactive oxygen species (ROS) and mitochondrial membrane potential of HCT-15 exposed to GA was assessed using 2’,7’-dichlorfluorescein-diacetate and rhodamine-123 respectively, with the help of flow cytometry. Morphological changes caused by GA treatment in the colon cancer cells were identified by scanning electron microscope and photomicrograph examination. Apoptosis was confirmed using flow cytometric analysis of GA treated HCT-15 cells after staining with Yo-Pro-1. RESULTS: MTT assay results illustrated that GA has an inhibitory effect on HCT-15 cells with IC50 value of 740 μmol/L. A time-dependent inhibition of colony formation was evident with GA treatment. Cell cycle arrest was evident from the accumulation of GA treated HCT-15 cells at sub-G1 phase (0.98 ± 1.03 vs 58.01 ± 2.05) with increasing exposure time. Flow cytometric analysis of GA treated HCT-15 cells depicted early events associated with apoptosis like lipid layer breakage and fall in mitochondrial membrane potential apart from an increase in the generation of ROS which were in a time dependent manner. SEM and photomicrograph images of the GA-treated cells displayed membrane blebbing and cell shrinking characteristics of apoptosis. Further apoptosis confirmation by Yo-Pro-1 staining also showed the time-dependent increase of apoptotic cells after treatment. CONCLUSION: These results show that GA induced ROS dependent apoptosis and inhibited the growth of colon cancer cells. PMID:27099438

  16. Translating tumor biology into personalized treatment planning: analytical performance characteristics of the Oncotype DX Colon Cancer Assay.

    Science.gov (United States)

    Clark-Langone, Kim M; Sangli, Chithra; Krishnakumar, Jayadevi; Watson, Drew

    2010-12-23

    The Oncotype DX Colon Cancer Assay is a new diagnostic test for determining the likelihood of recurrence in stage II colon cancer patients after surgical resection using fixed paraffin embedded (FPE) primary colon tumor tissue. Like the Oncotype DX Breast Cancer Assay, this is a high complexity, multi-analyte, reverse transcription (RT) polymerase chain reaction (PCR) assay that measures the expression levels of specific cancer-related genes. By capturing the biology underlying each patient's tumor, the Oncotype DX Colon Cancer Assay provides a Recurrence Score (RS) that reflects an individualized risk of disease recurrence. Here we describe its analytical performance using pre-determined performance criteria, which is a critical component of molecular diagnostic test validation. All analytical measurements met pre-specified performance criteria. PCR amplification efficiency for all 12 assays was high, ranging from 96% to 107%, while linearity was demonstrated over an 11 log2 concentration range for all assays. Based on estimated components of variance for FPE RNA pools, analytical reproducibility and precision demonstrated low SDs for individual genes (0.16 to 0.32 CTs), gene groups (≤ 0.05 normalized/aggregate CTs) and RS (≤ 1.38 RS units). Analytical performance characteristics shown here for both individual genes and gene groups in the Oncotype DX Colon Cancer Assay demonstrate consistent translation of specific biology of individual tumors into clinically useful diagnostic information. The results of these studies illustrate how the analytical capability of the Oncotype DX Colon Cancer Assay has enabled clinical validation of a test to determine individualized recurrence risk after colon cancer surgery.

  17. Implementation of the scientific evidence into daily practice - example from fast-track colonic cancer surgery

    DEFF Research Database (Denmark)

    Hammer, J.; Harling, H.; Wille-Jorgensen, P.

    2008-01-01

    Objective To report the implementation and results of fast-track surgery for colonic cancer in the daily routine. Method A total of 131 consecutive patients scheduled for elective colonic cancer resections entered a fast-track perioperative course after thorough information. The regimen contained...

  18. Diet, microbiota, and microbial metabolites in colon cancer risk in rural Africans and African Americans

    NARCIS (Netherlands)

    Ou, J.; Carbonero, F.; Zoetendal, E.G.; Delany, J.P.; Wang, M.; Newton, K.; Gaskins, H.R.; O'Keefe, S.F.

    2013-01-01

    BACKGROUND: Epidemiologic studies have suggested that most cases of sporadic colon cancer can be attributed to diet. The recognition that colonic microbiota have a major influence on colonic health suggests that they might mediate colonic carcinogenesis. OBJECTIVE: To examine the hypothesis that the

  19. CysLT(1)R antagonists inhibit tumor growth in a xenograft model of colon cancer.

    Science.gov (United States)

    Savari, Sayeh; Liu, Minghui; Zhang, Yuan; Sime, Wondossen; Sjölander, Anita

    2013-01-01

    The expression of the inflammatory G-protein coupled receptor CysLT1R has been shown to be upregulated in colon cancer patients and associated with poor prognosis. The present study investigated the correlation between CysLT1R and colon cancer development in vivo using CysLT1R antagonists (ZM198,615 or Montelukast) and the nude mouse xenograft model. Two drug administration regimens were established. The first regimen was established to investigate the importance of CysLT1R in tumor initiation. Nude mice were inoculated with 50 µM CysLT1R antagonist-pretreated HCT-116 colon cancer cells and received continued treatment (5 mg/kg/day, intraperitoneally). The second regimen aimed to address the role of CysLT1R in tumor progression. Nude mice were inoculated with non-pretreated HCT-116 cells and did not receive CysLT1R antagonist treatment until recordable tumor appearance. Both regimens resulted in significantly reduced tumor size, attributed to changes in proliferation and apoptosis as determined by reduced Ki-67 levels and increased levels of p21(WAF/Cip1) (Pcolon cancer cell line HCT-116 and CysLT1R antagonists. In addition to significant reductions in cell proliferation, adhesion and colony formation, we observed induction of cell cycle arrest and apoptosis in a dose-dependent manner. The ability of Montelukast to inhibit growth of human colon cancer xenograft was further validated by using two additional colon cancer cell lines, SW-480 and HT-29. Our results demonstrate that CysLT1R antagonists inhibit growth of colon cancer xenografts primarily by reducing proliferation and inducing apoptosis of the tumor cells.

  20. Radiation-induced colon cancer with high frequency microsatellite instability (MSI-H), report of a case

    International Nuclear Information System (INIS)

    Arai, Masami; Ueno, Masashi; Koizumi, Koichi

    2002-01-01

    We report a 67-year-old female with radiation-induced colon cancer which developed 23 years after radiation therapy for cancer of the endometrium. She was strongly suspected to be a case of hereditary nonpolyposis colorectal cancer (HNPCC) due to her clinical manifestations, i.e. metachronous multiple cancer developed in the endometrium and colon. MSI test and immunohistochemistry for mismatch repair (MMR) proteins revealed that MSI was highly positive and expression of hMSH2 was lost in the colon cancers. Further, on examining the genetic change, the point mutation, ACG→ATG, responsible for amino acid change, was detected in codon8 (exon1) of the hMSH2 gene. The change, however, could be a polymorphism of this gene and further analyses were necessitated to confirm the genetic background for HNPCC. Interestingly, three cancers with adenoma were located in the mucosa of radiation colitis, in which several atypical glands were also found. This is the only case of radiation-induced colorectal cancer with MSI-H in our hospital. Because of our previous studies, we believe that the genetic pathway in carcinogenesis of the radiation-induced colon cancer is different from that of HNPCC, despite their having several kinds of clinical and pathological features in common. (author)

  1. Radiation-induced colon cancer with high frequency microsatellite instability (MSI-H), report of a case

    Energy Technology Data Exchange (ETDEWEB)

    Arai, Masami; Ueno, Masashi; Koizumi, Koichi [Japanese Foundation for Cancer Research, Tokyo (Japan). Hospital] [and others

    2002-07-01

    We report a 67-year-old female with radiation-induced colon cancer which developed 23 years after radiation therapy for cancer of the endometrium. She was strongly suspected to be a case of hereditary nonpolyposis colorectal cancer (HNPCC) due to her clinical manifestations, i.e. metachronous multiple cancer developed in the endometrium and colon. MSI test and immunohistochemistry for mismatch repair (MMR) proteins revealed that MSI was highly positive and expression of hMSH2 was lost in the colon cancers. Further, on examining the genetic change, the point mutation, ACG{yields}ATG, responsible for amino acid change, was detected in codon8 (exon1) of the hMSH2 gene. The change, however, could be a polymorphism of this gene and further analyses were necessitated to confirm the genetic background for HNPCC. Interestingly, three cancers with adenoma were located in the mucosa of radiation colitis, in which several atypical glands were also found. This is the only case of radiation-induced colorectal cancer with MSI-H in our hospital. Because of our previous studies, we believe that the genetic pathway in carcinogenesis of the radiation-induced colon cancer is different from that of HNPCC, despite their having several kinds of clinical and pathological features in common. (author)

  2. Apalutamide treatment and metastasis-free survival in prostate cancer

    DEFF Research Database (Denmark)

    Smith, Matthew R.; Saad, Fred; Chowdhury, Simon

    2018-01-01

    BACKGROUND Apalutamide, a competitive inhibitor of the androgen receptor, is under development for the treatment of prostate cancer. We evaluated the efficacy of apalutamide in men with nonmetastatic castration-resistant prostate cancer who were at high risk for the development of metastasis....... METHODS We conducted a double-blind, placebo-controlled, phase 3 trial involving men with nonmetastatic castration-resistant prostate cancer and a prostate-specific antigen doubling time of 10 months or less. Patients were randomly assigned, in a 2:1 ratio, to receive apalutamide (240 mg per day...... and 7.0% in the placebo group. The following adverse events occurred at a higher rate with apalutamide than with placebo: rash (23.8% vs. 5.5%), hypothyroidism (8.1% vs. 2.0%), and fracture (11.7% vs. 6.5%). CONCLUSIONS Among men with nonmetastatic castration-resistant prostate cancer, metastasis...

  3. Effect of soy saponin on the growth of human colon cancer cells

    Science.gov (United States)

    Tsai, Cheng-Yu; Chen, Yue-Hwa; Chien, Yi-Wen; Huang, Wen-Hsuan; Lin, Shyh-Hsiang

    2010-01-01

    AIM: To investigate the effect of extracted soybean saponins on the growth of human colon cancer cells. METHODS: WiDr human colon cancer cells were treated with 150, 300, 600 or 1200 ppm of soy saponin to determine the effect on cell growth, cell morphology, alkaline phosphatase (AP) and protein kinase C (PKC) activities, and P53 protein, c-Fos and c-Jun gene expression. RESULTS: Soy saponin decreased the number of viable cells in a dose-dependent manner and suppressed 12-O-tetradecanol-phorbol-13-acetate-stimulated PKC activity (P saponins developed cytoplasmic vesicles and the cell membrane became rougher and more irregular in a dose-dependent manner, and eventually disassembled. At 600 and 1200 ppm, the activity of AP was increased (P saponin. CONCLUSION: Soy saponin may be effective in preventing colon cancer by affecting cell morphology, cell proliferation enzymes, and cell growth. PMID:20632438

  4. Apoptotic block in colon cancer cells may be rectified by lentivirus mediated overexpression of caspase-9.

    Science.gov (United States)

    Xu, D; Wang, C; Shen, X; Yu, Y; Rui, Y; Zhang, D; Zhou, Z

    2013-12-01

    At present, the inhibition of apoptosis during pathogenesis of colorectal cancer is widely recognized while the role of caspase-9 in this process remains controversial. We aimed to investigate the differential expression of caspase-9 and evaluate the therapeutic potential of expression intervention in this study. We first examined the different expression of caspase-9 in normal colon mucosa, adenoma and cancer, investigating the relationship between its expression and clinico-pathological characteristics. Secondly, overexpression of caspase-9 was established in colon cancer cell lines by lentivirus infection to study the changes in growth, proliferation and apoptosis. Compared with normal colon mucosa, the expression of caspase-9 was higher in adenoma while lower in cancer both at mRNA and protein level (P expression is more common in poorly differentiated cancers (P expression of caspase-9, poorer colony formation and slower cell proliferation. In terms of apoptosis related indicators, caspase-9 overexpression leads to higher apoptosis rate and GO/G1 arrest, while up-regulating the expression of caspase-3 (P expression from colon mucosa, adenoma to cancer suggested it may be involved in the carcinogenesis of colon cancer. The overexpression of caspase-9 exhibits an inhibitory role in cancer growth and proliferation while promoting apoptosis. However, a non-apoptotic role of caspase-9 facilitating differentiation was also implied.

  5. Managing Potentially Resectable Metastatic Colon Cancer

    OpenAIRE

    Marshall, John L.

    2008-01-01

    For patients with metastatic colon cancer, management has evolved from resecting a single liver metastasis and having only one chemotherapy medicine, to resecting multiple metastases including those outside the liver as well as using combination chemotherapy (based on recent supportive trials) to improve outcomes. This success has also raised many questions, including the role of adjuvant chemotherapy to downstage borderline resectable tumors, whether patients who receive preoperative chemoth...

  6. Double primary malignancies associated with colon cancer in patients with situs inversus totalis: two case reports

    Directory of Open Access Journals (Sweden)

    Kim Dae

    2011-09-01

    Full Text Available Abstract Situs inversus totalis (SIT is not itself a premalignant condition, however, rare synchronous or metachronous multiple primary malignancies have been reported. Herein we present a case of synchronous transverse and sigmoid colon cancers and a case of metachronous rectosigmoid colon and gastric cancers in patients with SIT. A 66-year-old male with SIT was referred for a two-month history of hematochezia. Synchronous colonic tumors were found on the proximal transverse and sigmoid colon. The patient underwent open total colectomy and was discharged without incident. A 71-year-old female with rectosigmoid colon cancer and SIT underwent laparoscopy-assisted low anterior resection. Fourteen months after the surgery, the patient developed a single hepatic metastasis and underwent hepatic segmentectomy (S6. Forty-six months after laparoscopy-assisted low anterior resection, the patient developed metachronous early gastric cancer on the antrum and underwent radical subtotal gastrectomy with gastroduodenostomy. The patient is doing well without recurrence for 28 months.

  7. Genetic variation in the transforming growth factor-β-signaling pathway, lifestyle factors, and risk of colon or rectal cancer.

    Science.gov (United States)

    Slattery, Martha L; Lundgreen, Abbie; Wolff, Roger K; Herrick, Jennifer S; Caan, Bette J

    2012-05-01

    The transforming growth factor-β-signaling pathway has been identified as being involved in colorectal cancer. The aim of this study was to determine how diet and lifestyle factors in combination with genetic variation in the transforming growth factor-β-signaling pathway alters colorectal cancer risk. We used data from 2 population-based case-control studies. Participants included patients with colon cancer (n = 1574) and controls (n = 1970) and patients with rectal cancer ( n = 791) and controls (n = 999). The primary outcomes measured were newly diagnosed cases of colon or rectal cancer. Colon and rectal cancer risk increased with the number of at-risk genotypes within the transforming growth factor-β-signaling pathway (OR 3.68, 95% CI 2.74,4.94 for colon cancer; OR 3.89, 95% CI 2.66,5.69 for rectal cancer). A high at-risk lifestyle score also resulted in significant increased risk with number of at-risk lifestyle factors (OR 2.99, 95% CI 2.32,3.85 for colon cancer; OR 3.37, 95% CI 2.24,5.07 for rectal cancer). The combination of high-risk genotype and high-risk lifestyle results in the greatest increase in risk (OR 7.89, 95% CI 4.45,13.96 for colon cancer; OR 8.75, 95% CI 3.66,20.89 for rectal cancer). The study results need validation in other large studies of colon and rectal cancer. In summary, our data suggest that there is increased colon and rectal cancer risk with increasing number of at-risk genotypes and at-risk lifestyle factors. Although the integrity of the pathway can be diminished by a number of high-risk genotypes, this risk can be offset, in part, by maintaining a healthy lifestyle.

  8. Identifying molecular subtypes in human colon cancer using gene expression and DNA methylation microarray data.

    Science.gov (United States)

    Ren, Zhonglu; Wang, Wenhui; Li, Jinming

    2016-02-01

    Identifying colon cancer subtypes based on molecular signatures may allow for a more rational, patient-specific approach to therapy in the future. Classifications using gene expression data have been attempted before with little concordance between the different studies carried out. In this study we aimed to uncover subtypes of colon cancer that have distinct biological characteristics and identify a set of novel biomarkers which could best reflect the clinical and/or biological characteristics of each subtype. Clustering analysis and discriminant analysis were utilized to discover the subtypes in two different molecular levels on 153 colon cancer samples from The Cancer Genome Atlas (TCGA) Data Portal. At gene expression level, we identified two major subtypes, ECL1 (expression cluster 1) and ECL2 (expression cluster 2) and a list of signature genes. Due to the heterogeneity of colon cancer, the subtype ECL1 can be further subdivided into three nested subclasses, and HOTAIR were found upregulated in subclass 2. At DNA methylation level, we uncovered three major subtypes, MCL1 (methylation cluster 1), MCL2 (methylation cluster 2) and MCL3 (methylation cluster 3). We found only three subtypes of CpG island methylator phenotype (CIMP) in colon cancer instead of the four subtypes in the previous reports, and we found no sufficient evidence to subdivide MCL3 into two distinct subgroups.

  9. Subtotal Colectomy for Colon Cancer Reduces the Need for Subsequent Surgery in Lynch Syndrome.

    Science.gov (United States)

    Renkonen-Sinisalo, Laura; Seppälä, Toni T; Järvinen, Heikki J; Mecklin, Jukka-Pekka

    2017-08-01

    The risk of metachronous colorectal cancer is high after surgical resection for first colon cancer in Lynch syndrome. This study aimed to examine whether extended surgery decreases the risk of subsequent colorectal cancer and improves long-term survival. This was a retrospective study. Data were collected from a nationwide registry. Two hundred forty-two Lynch syndrome pathogenic variant carriers who underwent surgery for a first colon cancer from 1984 to 2009 were included. Patients underwent standard segmental colectomy (n = 144) or extended colectomy (n = 98) for colon cancer. Patients were followed a median of 14.6 up to 25 years. Risk of subsequent colorectal cancer in either group, overall and disease-specific survival, and operative mortality were the primary outcomes measured. Subtotal colectomy decreased the risk of subsequent colorectal cancer (HR, 0.20; 95% CI, 0.08-0.52; p = 0.001), compared with segmental resection. Subsequent colorectal cancer decreased in MLH1 carriers. The MSH2 carriers showed no statistical difference, possibly because of their small number. Disease-specific and overall survival within 25 years did not differ between the standard and extended surgeries (82.7% vs 87.2%, p = 0.76 and 47.2% vs 41.4%, p = 0.83). The cumulative risk of subsequent colorectal cancer was 20% in 10 years and 47% within 25 years after standard resection and 4% and 9% after extended surgery. The cumulative risk of metachronous colorectal cancer was 7% within 25 years after subtotal colectomy with ileosigmoidal anastomosis. One patient died of postoperative septicemia within 30 days after segmental colectomy. Data on surgical procedures were primarily collected retrospectively. Lynch syndrome pathogenic variant carriers may undergo subtotal colectomy to manage first colon cancer and avoid repetitive abdominal surgery and to reduce the remaining bowel to facilitate easier endoscopic surveillance. It provides no survival benefit, compared with segmental colon

  10. Non-Metastatic Cutaneous Melanoma Induces Chronodisruption in Central and Peripheral Circadian Clocks.

    Science.gov (United States)

    de Assis, Leonardo Vinícius Monteiro; Moraes, Maria Nathália; Magalhães-Marques, Keila Karoline; Kinker, Gabriela Sarti; da Silveira Cruz-Machado, Sanseray; Castrucci, Ana Maria de Lauro

    2018-04-03

    The biological clock has received increasing interest due to its key role in regulating body homeostasis in a time-dependent manner. Cancer development and progression has been linked to a disrupted molecular clock; however, in melanoma, the role of the biological clock is largely unknown. We investigated the effects of the tumor on its micro- (TME) and macro-environments (TMaE) in a non-metastatic melanoma model. C57BL/6J mice were inoculated with murine B16-F10 melanoma cells and 2 weeks later the animals were euthanized every 6 h during 24 h. The presence of a localized tumor significantly impaired the biological clock of tumor-adjacent skin and affected the oscillatory expression of genes involved in light- and thermo-reception, proliferation, melanogenesis, and DNA repair. The expression of tumor molecular clock was significantly reduced compared to healthy skin but still displayed an oscillatory profile. We were able to cluster the affected genes using a human database and distinguish between primary melanoma and healthy skin. The molecular clocks of lungs and liver (common sites of metastasis), and the suprachiasmatic nucleus (SCN) were significantly affected by tumor presence, leading to chronodisruption in each organ. Taken altogether, the presence of non-metastatic melanoma significantly impairs the organism's biological clocks. We suggest that the clock alterations found in TME and TMaE could impact development, progression, and metastasis of melanoma; thus, making the molecular clock an interesting pharmacological target.

  11. Non-Metastatic Cutaneous Melanoma Induces Chronodisruption in Central and Peripheral Circadian Clocks

    Directory of Open Access Journals (Sweden)

    Leonardo Vinícius Monteiro de Assis

    2018-04-01

    Full Text Available The biological clock has received increasing interest due to its key role in regulating body homeostasis in a time-dependent manner. Cancer development and progression has been linked to a disrupted molecular clock; however, in melanoma, the role of the biological clock is largely unknown. We investigated the effects of the tumor on its micro- (TME and macro-environments (TMaE in a non-metastatic melanoma model. C57BL/6J mice were inoculated with murine B16-F10 melanoma cells and 2 weeks later the animals were euthanized every 6 h during 24 h. The presence of a localized tumor significantly impaired the biological clock of tumor-adjacent skin and affected the oscillatory expression of genes involved in light- and thermo-reception, proliferation, melanogenesis, and DNA repair. The expression of tumor molecular clock was significantly reduced compared to healthy skin but still displayed an oscillatory profile. We were able to cluster the affected genes using a human database and distinguish between primary melanoma and healthy skin. The molecular clocks of lungs and liver (common sites of metastasis, and the suprachiasmatic nucleus (SCN were significantly affected by tumor presence, leading to chronodisruption in each organ. Taken altogether, the presence of non-metastatic melanoma significantly impairs the organism’s biological clocks. We suggest that the clock alterations found in TME and TMaE could impact development, progression, and metastasis of melanoma; thus, making the molecular clock an interesting pharmacological target.

  12. Management of locally advanced and metastatic colon cancer in elderly patients.

    Science.gov (United States)

    Kurniali, Peter C; Hrinczenko, Borys; Al-Janadi, Anas

    2014-02-28

    Colon cancer is the second leading cause of cancer mortality in the United States with a median age at diagnosis of 69 years. Sixty percent are diagnosed over the age of 65 years and 36% are 75 years or older. At diagnosis, approximately 58% of patients will have locally advanced and metastatic disease, for which systemic chemotherapy has been shown to improve survival. Treatment of cancer in elderly patients is more challenging due to multiple factors, including disabling co-morbidities as well as a decline in organ function. Cancer treatment of elderly patients is often associated with more toxicities that may lead to frequent hospitalizations. In locally advanced disease, fewer older patients receive adjuvant chemotherapy despite survival benefit and similar toxicity when compared to their younger counterparts. A survival benefit is also observed in the palliative chemotherapy setting for elderly patients with metastatic disease. When treating elderly patients with colon cancer, one has to consider drug pharmacokinetics and pharmacodynamics. Since chronological age is a poor marker of a patient's functional status, several methods of functional assessment including performance status and activities of daily living (ADL) or instrumental ADL, or even a comprehensive geriatric assessment, may be used. There is no ideal chemotherapy regimen that fits all elderly patients and so a regimen needs to be tailored for each individual. Important considerations when treating elderly patients include convenience and tolerability. This review will discuss approaches to the management of elderly patients with locally advanced and metastatic colon cancer.

  13. Chemopreventive properties of raisins originating from Greece in colon cancer cells.

    Science.gov (United States)

    Kountouri, Aggeliki M; Gioxari, Aristea; Karvela, Evangelia; Kaliora, Andriana C; Karvelas, Michalis; Karathanos, Vaios T

    2013-02-26

    Colorectal cancer is one of the major causes of cancer-related mortality in humans in both developed and developing countries. Dietary patterns influence the risk of colon cancer development, while plant-derived foods have gained great interest, due to the high content of antioxidants. Corinthian raisins (Currants, CR) and Sultanas (S) (Vitis vinifera L., Vitaceae) are dried vine fruits produced in Greece with many culinary uses in both the Mediterranean and the Western nutrition. In the present study, we investigated the effects of CR and S on human colon cancer cells. Methanol extracts of CR and S were used at different concentrations. The total polyphenol content and anti-radical activity were measured by Folin-Ciocalteu and DPPH, respectively. Antioxidant, anti-inflammatory and anti-proliferative effects on HT29 cell culture were evaluated. All extracts exhibited DPPH˙ scavenging activity in a dose-dependent manner. Both products suppressed cell proliferation, while the levels of glutathione and cyclooxygenase 2 were significantly decreased. A significant reduction in IL-8 levels and NF-kappaB p65 activation was also observed. Both antioxidant and anti-inflammatory effects were dependent on the duration of exposure. Results indicate that the methanol extracts of CR and S exhibit anti-radical activity in vitro, as well as cancer preventive efficacy on colon cancer cells, with S having slightly higher activity. The beneficial properties of these unique dried grapes are attributed to their high content of phenolic compounds.

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

    NARCIS (Netherlands)

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

    1995-01-01

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

  15. Comparative study of oncologic outcomes for laparoscopic vs. open surgery in transverse colon cancer.

    Science.gov (United States)

    Kim, Woo Ram; Baek, Se Jin; Kim, Chang Woo; Jang, Hyun A; Cho, Min Soo; Bae, Sung Uk; Hur, Hyuk; Min, Byung Soh; Baik, Seung Hyuk; Lee, Kang Young; Kim, Nam Kyu; Sohn, Seung Kuk

    2014-01-01

    Laparoscopic resection for transverse colon cancer is a technically challenging procedure that has been excluded from various large randomized controlled trials of which the long-term outcomes still need to be verified. The purpose of this study was to evaluate long-term oncologic outcomes for transverse colon cancer patients undergoing laparoscopic colectomy (LAC) or open colectomy (OC). This retrospective review included patients with transverse colon cancer who received a colectomy between January 2006 and December 2010. Short-term and five-year oncologic outcomes were compared between these groups. A total of 131 patients were analyzed in the final study (LAC, 84 patients; OC, 47 patients). There were no significant differences in age, gender, body mass index, tumor location, operative procedure, or blood loss between groups, but the mean operative time in LAC was significantly longer (LAC, 246.8 minutes vs. OC, 213.8 minutes; P = 0.03). Hospital stay was much shorter for LAC than OC (9.1 days vs. 14.5 days, P transverse colon cancer is feasible and safe with comparable short- and long-term outcomes.

  16. Colon Cancer Tumorigenesis Initiated by the H1047R Mutant PI3K.

    Directory of Open Access Journals (Sweden)

    Alexander E Yueh

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

  17. The prognosis significance and application value of peritoneal elastic lamina invasion in colon cancer.

    Science.gov (United States)

    Lu, Jun; Hu, Xiumei; Meng, Yutong; Zhao, Hongying; Cao, Qing; Jin, Mulan

    2018-01-01

    The aims of this study were to evaluate the associations between peritoneal elastic lamina invasion (ELI) and the clinicopathological prognostic factors of colon cancer, to evaluate the feasibility of ELI with use of an elastic stain to help diagnose serosal invasion of colon cancer in routine practice, so as to help us to provide a more accurate estimate for prognosis and stage of patients and a marker for postoperative treatment. 254 cases with colon cancer were included in the study. According to the presence of elastic lamina (EL) and elastic lamina invasion (ELI), all cases were divided into four groups: pT3 EL negative (pT3 EL (-)), pT3 ELI positive (pT3 ELI (+)), pT3 ELI negative (pT3 ELI (-)) and pT4a. Statistical analysis was used to analyze the relationship between elastic lamina invasion and other established adverse histologic features. The EL and ELI positive rates were 81.5% and 42.1% respectively. There were significant differences in mph node metastasis, venous invasion and tumor buds between pT3 ELI (-) and pT3 ELI (+), pT3 ELI (-) and pT4a. There was no significant difference in same factors between pT3 ELI (+) and pT4a. In pT3 stage, there were significant differences in lymph node metastasis, perineural invasion and tumor buds between EL (-) and ELI (+). There were no significant differences in same factors between EL (-) and ELI (-). EL was detected less frequently in right-sided tumors compared with left-sided tumors. ELI might be the prognostic factors of colon cancer with II stage and might be the marker of postoperative adjuvant chemotherapy. Patients with pT3 ELI (+) might have similar prognosis to patients with pT4a. For patients with pT3 colon cancer, EL(-) might have similar prognosis as ELI (-) and might take the same therapy. In addition, the right half colon EL positive rate was lower than the left colon. Elastic staining might be a useful tool to help determine the invasive depth and stage of colon cancer.

  18. Adjuvant chemotherapy is associated with improved survival in patients with stage II colon cancer.

    Science.gov (United States)

    Casadaban, Leigh; Rauscher, Garth; Aklilu, Mebea; Villenes, Dana; Freels, Sally; Maker, Ajay V

    2016-11-15

    The role of adjuvant chemotherapy in patients with stage II colon cancer remains to be elucidated and its use varies between patients and institutions. Currently, clinical guidelines suggest discussing adjuvant chemotherapy for patients with high-risk stage II disease in the absence of conclusive randomized controlled trial data. To further investigate this relationship, the objective of the current study was to determine whether an association exists between overall survival (OS) and adjuvant chemotherapy in patients stratified by age and pathological risk features. Data from the National Cancer Data Base were analyzed for demographics, tumor characteristics, management, and survival of patients with stage II colon cancer who were diagnosed from 1998 to 2006 with survival information through 2011. Pearson Chi-square tests and binary logistic regression were used to analyze disease and demographic data. Survival analysis was performed with the log-rank test and Cox proportional hazards regression modeling. Propensity score weighting was used to match cohorts. Among 153,110 patients with stage II colon cancer, predictors of receiving chemotherapy included age clinically relevant OS was associated with the receipt of adjuvant chemotherapy in all patient subgroups regardless of high-risk tumor pathologic features (poor or undifferentiated histology, colon cancer evaluated to date, improved OS was found to be associated with adjuvant chemotherapy regardless of treatment regimen, patient age, or high-risk pathologic risk features. Cancer 2016;122:3277-3287. © 2016 American Cancer Society. © 2016 American Cancer Society.

  19. Circulating exosomal microRNAs as biomarkers of colon cancer.

    Directory of Open Access Journals (Sweden)

    Hiroko Ogata-Kawata

    Full Text Available PURPOSE: Exosomal microRNAs (miRNAs have been attracting major interest as potential diagnostic biomarkers of cancer. The aim of this study was to characterize the miRNA profiles of serum exosomes and to identify those that are altered in colorectal cancer (CRC. To evaluate their use as diagnostic biomarkers, the relationship between specific exosomal miRNA levels and pathological changes of patients, including disease stage and tumor resection, was examined. EXPERIMENTAL DESIGN: Microarray analyses of miRNAs in exosome-enriched fractions of serum samples from 88 primary CRC patients and 11 healthy controls were performed. The expression levels of miRNAs in the culture medium of five colon cancer cell lines were also compared with those in the culture medium of a normal colon-derived cell line. The expression profiles of miRNAs that were differentially expressed between CRC and control sample sets were verified using 29 paired samples from post-tumor resection patients. The sensitivities of selected miRNAs as biomarkers of CRC were evaluated and compared with those of known tumor markers (CA19-9 and CEA using a receiver operating characteristic analysis. The expression levels of selected miRNAs were also validated by quantitative real-time RT-PCR analyses of an independent set of 13 CRC patients. RESULTS: The serum exosomal levels of seven miRNAs (let-7a, miR-1229, miR-1246, miR-150, miR-21, miR-223, and miR-23a were significantly higher in primary CRC patients, even those with early stage disease, than in healthy controls, and were significantly down-regulated after surgical resection of tumors. These miRNAs were also secreted at significantly higher levels by colon cancer cell lines than by a normal colon-derived cell line. The high sensitivities of the seven selected exosomal miRNAs were confirmed by a receiver operating characteristic analysis. CONCLUSION: Exosomal miRNA signatures appear to mirror pathological changes of CRC patients and

  20. Intake of dietary fiber, especially from cereal foods, is associated with lower incidence of colon cancer in the HELGA cohort

    DEFF Research Database (Denmark)

    Hansen, Louise; Skeie, Guri; Landberg, Rikard

    2012-01-01

    The role of dietary fiber on the risk of colon and rectal cancer has been investigated in numerous studies, but findings have been inconsistent. The purpose of this study was to examine associations between intake of dietary fiber and risk of incident colon (including distal and proximal colon......-specific incidence rate ratios (IRRs) of colon and rectal cancer were related to intake of total or specific fiber source using Cox proportional hazards models. For men, an inverse association was observed between intake of total fiber and the risk of colon cancer per an incremental increase of 10 g day(-1) , IRR...... fiber per 2 g day(-1) was also associated with lower risk of colon cancer, 0.97 (0.93-1.00). No clear associations were seen for rectal cancer. Our data indicate a protective role of total and cereal fiber intake, particularly from cereal foods with high fiber content, in the prevention of colon cancer....

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

    Directory of Open Access Journals (Sweden)

    Martha L Slattery

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

  2. Radiation enteritis. A rare complication of the transverse colon in uterine cancer

    International Nuclear Information System (INIS)

    Yoshimura, Kenji; Hirata, Ichiro; Maemura, Kentaro; Sugi, Kazunori; Tahara, Tetsuo

    2000-01-01

    Radiation therapy is a powerful method for the control of cancer. The utilization of abdominal or pelvic radiation has been extended, and the incidence of radiation enteritis appears to be increasing. The majority of the induced lesions is in the distal ileum, sigmoid colon, or rectum. Reported here is an unusual case of radiation enteritis which caused a severe sequelae of stricture in the transverse colon as a long-term effect of therapeutic irradiation for uterine cancer, and required a surgical resection. (author)

  3. Radiation enteritis. A rare complication of the transverse colon in uterine cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yoshimura, Kenji [Kodama Hospital, Takarazuka, Hyogo (Japan); Hirata, Ichiro; Maemura, Kentaro; Sugi, Kazunori; Tahara, Tetsuo

    2000-12-01

    Radiation therapy is a powerful method for the control of cancer. The utilization of abdominal or pelvic radiation has been extended, and the incidence of radiation enteritis appears to be increasing. The majority of the induced lesions is in the distal ileum, sigmoid colon, or rectum. Reported here is an unusual case of radiation enteritis which caused a severe sequelae of stricture in the transverse colon as a long-term effect of therapeutic irradiation for uterine cancer, and required a surgical resection. (author)

  4. Anastomotic Leak Increases Distant Recurrence and Long-Term Mortality After Curative Resection for Colonic Cancer

    DEFF Research Database (Denmark)

    Krarup, Peter-Martin; Nordholm-Carstensen, Andreas; Jorgensen, Lars N

    2014-01-01

    OBJECTIVE: To investigate the impact of anastomotic leak (AL) on disease recurrence and long-term mortality in patients alive 120 days after curative resection for colonic cancer. BACKGROUND: There is no solid data as to whether AL after colonic cancer surgery increases the risk of disease...

  5. Upregulated expression of human neutrophil peptides 1, 2 and 3 (HNP 1-3) in colon cancer serum and tumours

    DEFF Research Database (Denmark)

    Albrethsen, Jakob; Bøgebo, Rikke; Gammeltoft, Steen

    2005-01-01

    of identifying biomarkers for colon cancer. METHODS: By Surface Enhanced Laser Desorption/Ionisation--Time Of Flight/Mass spectrometry (SELDI-TOF/MS) we compare the protein profiles of colon cancer serum with serum from healthy individuals and the protein profiles of colon tumours with normal colon tissue...

  6. MIS in the management of colon and rectal cancer: consensus meeting of the Colorectal Cancer Association of Canada.

    Science.gov (United States)

    Schlachta, Christopher M; Ashamalla, Shady; Smith, Andy

    2013-11-01

    A consensus conference on the role of minimally invasive surgery (MIS) in the management of colon and rectal cancer was convened by the Colorectal Cancer Association of Canada in Toronto on April 18, 2012. This is a report of the consensus of an invited group of Canadian experts in MIS and surgery of the colon and rectum that addresses the role this technology should play in treatment and also considers advocacy and resources.

  7. Evaluation of clinical, laboratory and morphologic prognostic factors in colon cancer

    Directory of Open Access Journals (Sweden)

    Nigro Casimiro

    2008-09-01

    Full Text Available Abstract Background The long-term prognosis of patients with colon cancer is dependent on many factors. To investigate the influence of a series of clinical, laboratory and morphological variables on prognosis of colon carcinoma we conducted a retrospective analysis of our data. Methods Ninety-two patients with colon cancer, who underwent surgical resection between January 1999 and December 2001, were analyzed. On survival analysis, demographics, clinical, laboratory and pathomorphological parameters were tested for their potential prognostic value. Furthermore, univariate and multivariate analysis of the above mentioned data were performed considering the depth of tumour invasion into the bowel wall as independent variable. Results On survival analysis we found that depth of tumour invasion (P Conclusion The various clinical, laboratory and patho-morphological parameters showed different prognostic value for colon carcinoma. In the future, preoperative prognostic markers will probably gain relevance in order to make a proper choice between surgery, chemotherapy and radiotherapy. Nevertheless, current data do not provide sufficient evidence for preoperative stratification of high and low risk patients. Further assessments in prospective large studies are warranted.

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

    NARCIS (Netherlands)

    Bordonaro, M.; Venema, K.; Putri, A.K.; Lazarova, D.

    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

  9. Translating tumor biology into personalized treatment planning: analytical performance characteristics of the Oncotype DX® Colon Cancer Assay

    International Nuclear Information System (INIS)

    Clark-Langone, Kim M; Sangli, Chithra; Krishnakumar, Jayadevi; Watson, Drew

    2010-01-01

    The Oncotype DX ® Colon Cancer Assay is a new diagnostic test for determining the likelihood of recurrence in stage II colon cancer patients after surgical resection using fixed paraffin embedded (FPE) primary colon tumor tissue. Like the Oncotype DX Breast Cancer Assay, this is a high complexity, multi-analyte, reverse transcription (RT) polymerase chain reaction (PCR) assay that measures the expression levels of specific cancer-related genes. By capturing the biology underlying each patient's tumor, the Oncotype DX Colon Cancer Assay provides a Recurrence Score (RS) that reflects an individualized risk of disease recurrence. Here we describe its analytical performance using pre-determined performance criteria, which is a critical component of molecular diagnostic test validation. All analytical measurements met pre-specified performance criteria. PCR amplification efficiency for all 12 assays was high, ranging from 96% to 107%, while linearity was demonstrated over an 11 log 2 concentration range for all assays. Based on estimated components of variance for FPE RNA pools, analytical reproducibility and precision demonstrated low SDs for individual genes (0.16 to 0.32 C T s), gene groups (≤0.05 normalized/aggregate C T s) and RS (≤1.38 RS units). Analytical performance characteristics shown here for both individual genes and gene groups in the Oncotype DX Colon Cancer Assay demonstrate consistent translation of specific biology of individual tumors into clinically useful diagnostic information. The results of these studies illustrate how the analytical capability of the Oncotype DX Colon Cancer Assay has enabled clinical validation of a test to determine individualized recurrence risk after colon cancer surgery

  10. Translating tumor biology into personalized treatment planning: analytical performance characteristics of the Oncotype DX® Colon Cancer Assay

    Directory of Open Access Journals (Sweden)

    Krishnakumar Jayadevi

    2010-12-01

    Full Text Available Abstract Background The Oncotype DX® Colon Cancer Assay is a new diagnostic test for determining the likelihood of recurrence in stage II colon cancer patients after surgical resection using fixed paraffin embedded (FPE primary colon tumor tissue. Like the Oncotype DX Breast Cancer Assay, this is a high complexity, multi-analyte, reverse transcription (RT polymerase chain reaction (PCR assay that measures the expression levels of specific cancer-related genes. By capturing the biology underlying each patient's tumor, the Oncotype DX Colon Cancer Assay provides a Recurrence Score (RS that reflects an individualized risk of disease recurrence. Here we describe its analytical performance using pre-determined performance criteria, which is a critical component of molecular diagnostic test validation. Results All analytical measurements met pre-specified performance criteria. PCR amplification efficiency for all 12 assays was high, ranging from 96% to 107%, while linearity was demonstrated over an 11 log2 concentration range for all assays. Based on estimated components of variance for FPE RNA pools, analytical reproducibility and precision demonstrated low SDs for individual genes (0.16 to 0.32 CTs, gene groups (≤0.05 normalized/aggregate CTs and RS (≤1.38 RS units. Conclusions Analytical performance characteristics shown here for both individual genes and gene groups in the Oncotype DX Colon Cancer Assay demonstrate consistent translation of specific biology of individual tumors into clinically useful diagnostic information. The results of these studies illustrate how the analytical capability of the Oncotype DX Colon Cancer Assay has enabled clinical validation of a test to determine individualized recurrence risk after colon cancer surgery.

  11. Neoadjuvant chemotherapy among patients treated for nonmetastatic breast cancer in a population with a high HIV prevalence in Johannesburg, South Africa

    Directory of Open Access Journals (Sweden)

    Ruff P

    2018-02-01

    Full Text Available Paul Ruff,1,2 Herbert Cubasch,2,3 Maureen Joffe,2,4 Evan Rosenbaum,5 Nivashni Murugan,2,3 Ming-Chih Tsai,2,3 Oluwatosin Ayeni,2 Katherine D Crew,5–7 Judith S Jacobson,6,7 Alfred I Neugut5–7 1Division of Medical Oncology, Department of Internal Medicine, University of the Witwatersrand, Faculty of Health Sciences, 2Noncommunicable Diseases Research Division, Wits Health Consortium, University of the Witwatersrand, Faculty of Health Sciences, 3Department of Surgery, Chris Hani Baragwanath Academic Hospital and University of the Witwatersrand, Faculty of Health Sciences, 4MRC Developmental Pathways of Health Research Unit, Department of Paediatrics, University of Witwatersrand, Faculty of Health Sciences, Johannesburg, South Africa; 5Department of Medicine, College of Physicians and Surgeons, Columbia University, 6Herbert Irving Comprehensive Cancer Center, Columbia University, 7Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA Background: Neoadjuvant (primary chemotherapy (NACT is the standard of care for locally advanced breast cancer. It also allows for the short-term assessment of chemotherapy response; a pathological complete responses correspond to improved long-term breast cancer outcomes. In sub-Saharan Africa, many patients are diagnosed with large nonresectable tumors. We examined NACT use in breast cancer patients who visited public hospitals in Johannesburg, South Africa. Methods: We assessed demographic characteristics, tumor stage and grade, hormone receptor status, and human immunodeficiency virus (HIV status of female patients diagnosed with nonmetastatic invasive carcinoma of the breast at Chris Hani Baragwanath Academic Hospital between January 1, 2009, and December 31, 2011. The patients received neoadjuvant, adjuvant, or no chemotherapy. Trastuzumab was unavailable. We developed logistic regression models to analyze the factors associated with NACT receipt in these patients

  12. A population-based comparison of 30-day readmission after surgery for colon and rectal cancer: How are they different?

    Science.gov (United States)

    Doumouras, Aristithes G; Tsao, Miriam W; Saleh, Fady; Hong, Dennis

    2016-09-01

    An implicit assumption in the analysis of colorectal readmission is that colon and rectal cancer patients are similar enough to analyze together. However, no studies have examined this assumption and whether substantial differences exist between colon and rectal cancer patients. This was a retrospective analysis of the differences in predictors, diagnoses, and costs of readmission between colon and rectal cancer cohorts for 30-day readmission. This study included all patients aged >18 who received an elective colectomy or low anterior resection for colorectal cancer from April 2008 until March 2012 in the province of Ontario. Overall, 13,571 patients were identified and the readmission rates significantly differed between rectal and colon cancer patients (7.1% colon and 10.7% rectal P = 0.001). Diabetes, age, and discharge to long term care were significantly different among colon and rectal patients in the prediction of readmission. Readmission for renal and stoma causes was more prominent in the rectal cohort. The adjusted cost difference for readmission did not significantly differ between rectal and colon cancer $178 ($1,924-1,568 P = 0.84) CONCLUSION: Several important differences in predictors and diagnoses exist between the two cohorts. Conversely, the costs associated with readmission were homogenous between rectal and colon cancer patients. J. Surg. Oncol. 2016;114:354-360. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Surgical resection of locally advanced primary transverse colon cancer--not a worse outcome in stage II tumor.

    Science.gov (United States)

    Hung, Hsin-Yuan; Yeh, Chien-Yuh; Changchien, Chung-Rong; Chen, Jinn-Shiun; Fan, Chung-Wei; Tang, Reiping; Hsieh, Pao-Shiu; Tasi, Wen-Sy; You, Yau-Tong; You, Jeng-Fu; Wang, Jeng-Yi; Chiang, Jy-Ming

    2011-07-01

    In locally advanced primary transverse colon cancer, a tumor may cause perforation or invade adjacent organs. Extensive resection is the best choice of treatment, but such procedures must be weighed against the potential survival benefits. This study was performed to identify the clinicopathological features and treatment outcomes of such tumors. We retrospectively reviewed the database of the Colorectal Cancer Registry of Chang Gung Memorial Hospital between February 1995 and December 2005. Patients with colon cancer sited between the hepatic and splenic flexure that involved an adjacent organ without distant metastasis were defined as having locally advanced transverse colon cancer. A total of 827 patients who underwent surgery for transverse primary colon cancer were enrolled in the study. Stage II and stage III colon cancer were diagnosed in 548 patients. Thirty-two (5.8%) patients were diagnosed with locally advanced tumors. Multivariate analysis revealed that stage III, preoperative carcinoembryonic antigen ≥5 ng/mL, a tumor with perforation or obstruction, and the presence of a locally advanced tumor were significant prognostic factors for both overall and cancer-specific survival. Postoperative morbidity rates differed significantly between the locally advanced and non-locally advanced tumor groups (22.7% vs. 12.3%, P transverse colon tumors (P = 0.21). Surgical resection of locally advanced transverse colon tumors resulted in a higher morbidity and mortality than that of non-locally advanced tumors, but the benefit of extensive surgery in the case of locally advanced tumors cannot be underestimated. Furthermore, this benefit is more pronounced in the case of stage II tumors.

  14. Complex of MUC1, CIN85 and Cbl in Colon Cancer Progression and Metastasis

    International Nuclear Information System (INIS)

    Cascio, Sandra; Finn, Olivera J.

    2015-01-01

    We previously reported that CIN85, an 85 KDa protein known to be involved in tumor cell migration and metastasis through its interaction with Cbl, associates with MUC1 in tumor cells. MUC1/CIN85 complex also regulates migration and invasion of tumor cells in vitro. Here, we examined specifically human colon carcinoma tissue microarrays (TMA) by immunohistochemistry for the expression of MUC1 and CIN85 and their potential role in cancer progression and metastasis. We detected a significant increase in expression of both MUC1 and CIN85 associated with advanced tumor stage and lymph node metastasis. We further investigated if Cbl could also be present in the MUC1/CIN85 complex. Co-immunoprecipitation assay showed that Cbl co-localized both with CIN85 and with MUC1 in a human colon cancer cell line. To begin to investigate the in vivo relevance of MUC1 overexpression and association with CIN85 and Cbl in cancer development and progression, we used human MUC1 transgenic mice that express MUC1 on the colonic epithelial cells, treated with azoxymethane to initiate and dextran sulfate sodium (AOM/DSS) to promote colorectal carcinogenesis. MUC1.Tg mice showed higher tumor incidence and decreased survival when compared with wild-type mice. Consistent with the in vitro data, the association of MUC1, CIN85 and Cbl was detected in colon tissues of AOM/DSS-treated MUC1 transgenic mice. MUC1/CIN85/Cbl complex appears to contribute to promotion and progression of colon cancer and thus increased expression of MUC1, CIN85 and Cbl in early stage colon cancer might be predictive of poor prognosis

  15. Complex of MUC1, CIN85 and Cbl in Colon Cancer Progression and Metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Cascio, Sandra, E-mail: sac131@pitt.edu [Department of Immunology, University of Pittsburgh School of Medicine, E1040 Biomedical Science Tower, Pittsburgh, PA 15261 (United States); Fondazione Ri.Med, via Bandiera, Palermo 90133 (Italy); Finn, Olivera J., E-mail: sac131@pitt.edu [Department of Immunology, University of Pittsburgh School of Medicine, E1040 Biomedical Science Tower, Pittsburgh, PA 15261 (United States)

    2015-02-10

    We previously reported that CIN85, an 85 KDa protein known to be involved in tumor cell migration and metastasis through its interaction with Cbl, associates with MUC1 in tumor cells. MUC1/CIN85 complex also regulates migration and invasion of tumor cells in vitro. Here, we examined specifically human colon carcinoma tissue microarrays (TMA) by immunohistochemistry for the expression of MUC1 and CIN85 and their potential role in cancer progression and metastasis. We detected a significant increase in expression of both MUC1 and CIN85 associated with advanced tumor stage and lymph node metastasis. We further investigated if Cbl could also be present in the MUC1/CIN85 complex. Co-immunoprecipitation assay showed that Cbl co-localized both with CIN85 and with MUC1 in a human colon cancer cell line. To begin to investigate the in vivo relevance of MUC1 overexpression and association with CIN85 and Cbl in cancer development and progression, we used human MUC1 transgenic mice that express MUC1 on the colonic epithelial cells, treated with azoxymethane to initiate and dextran sulfate sodium (AOM/DSS) to promote colorectal carcinogenesis. MUC1.Tg mice showed higher tumor incidence and decreased survival when compared with wild-type mice. Consistent with the in vitro data, the association of MUC1, CIN85 and Cbl was detected in colon tissues of AOM/DSS-treated MUC1 transgenic mice. MUC1/CIN85/Cbl complex appears to contribute to promotion and progression of colon cancer and thus increased expression of MUC1, CIN85 and Cbl in early stage colon cancer might be predictive of poor prognosis.

  16. MicroRNA-145 targets YES and STAT1 in colon cancer cells

    DEFF Research Database (Denmark)

    Gregersen, Lea H; Jacobsen, Anders B; Frankel, Lisa

    2010-01-01

    miRNA overexpression. Gene Ontology analysis showed an overrepresentation of genes involved in cell death, cellular growth and proliferation, cell cycle, gene expression and cancer. A number of the identified miRNA targets have previously been implicated in cancer, including YES, FSCN1, ADAM17, BIRC2......, VANGL1 as well as the transcription factor STAT1. Both YES and STAT1 were verified as direct miR-145 targets. CONCLUSIONS/SIGNIFICANCE: The study identifies and validates new cancer-relevant direct targets of miR-145 in colon cancer cells and hereby adds important mechanistic understanding of the tumor......BACKGROUND: MicroRNAs (miRNAs) have emerged as important gene regulators and are recognized as key players in tumorigenesis. miR-145 is reported to be down-regulated in several cancers, but knowledge of its targets in colon cancer remains limited. METHODOLOGY/PRINCIPAL FINDINGS: To investigate...

  17. Inhibitory effect of gene combination in a mouse model of colon cancer with liver metastasis.

    Science.gov (United States)

    DU, Tong; Niu, Hongxin

    2014-09-01

    The aim of the present study was to establish an animal liver metastasis model with human colon cancer and investigate the inhibitory effect of the wild type (WT) p53 gene combined with thymidine kinase/ganciclovir (TK/GCV) and cytosine deaminase/5-fluorocytosine (CD/5-FC) systems on liver metastasis of colon cancer. A nude mouse liver metastasis model with human colon cancer was established via a spleen cultivation method. A total of 32 nude mice were randomly divided into four groups, each group with eight mice. Group 1 mice received splenic injections of SW480 cells (control group), while group 2 mice were injected with SW480/p53 cells in the spleen. Group 3 mice were administered splenic injections of SW480/TK-CD cells, and GCV and 5-FC were injected into the abdominal cavity. Finally, group 4 mice received splenic injections of SW480/p53 cells mixed in equal proportion with SW480/TK-CD cells, as well as GCV and 5-FC injections in the abdominal cavity. These cells described were constructed in our laboratory and other laboratories. The number of liver metastatic tumors, the liver metastasis rate, conventional pathology, electron microscopy and other indicators in the nude mice of each group were compared and observed. The nude mouse liver metastasis model with human colon cancer was successfully established; the liver metastasis rate of the control group was 100%. The results demonstrated that the rate of liver metastasis in the nude mice in each treatment group decreased, as well as the average number of liver metastatic tumors. Furthermore, the effect of the treatment group with genetic combination (group 4) was the most effective, demonstrating that WTp53 had a synergistic effect with TK/GCV and CD/5-FC. Therefore, the present study successfully established a mouse model of liver metastasis with colon cancer by injecting human colon cancer cells in the spleen. Combined gene therapy was shown to have a synergistic effect, which effectively inhibited the

  18. Differential Expression of Ccn4 and Other Genes Between Metastatic and Non-metastatic EL4 Mouse Lymphoma Cells

    OpenAIRE

    S. CHAHAL, MANPREET; TERESA KU, H.; ZHANG, ZHIHONG; M. LEGASPI, CHRISTIAN; LUO, ANGELA; M. HOPKINS, MANDI; E. MEIER, KATHRYN

    2016-01-01

    Background: Previous work characterized variants of the EL4 murine lymphoma cell line. Some are non-metastatic, and others metastatic, in syngenic mice. In addition, metastatic EL4 cells were stably transfected with phospholipase D2 (PLD2), which further enhanced metastasis. Materials and Methods: Microarray analyses of mRNA expression was performed for non-metastatic, metastatic, and PLD2-expressing metastatic EL4 cells. Results: Many differences were observed between non-metastatic and meta...

  19. miR-136 targets MIEN1 and involves the metastasis of colon cancer by suppressing epithelial-to-mesenchymal transition

    Directory of Open Access Journals (Sweden)

    Ren H

    2017-12-01

    Full Text Available Haipeng Ren,1 Yuanling Qi,1 Xiaoyan Yin,2 Jianfeng Gao1 1Department of Internal Medicine of Oncology, People’s Hospital of Weifang, Weifang, 2Health and Family Planning Bureau of Weifang, Shouguang, People’s Republic of China Abstract: MIEN1 is a novel oncogene, and it involves tumor progression in various cancer types, including colon cancer. However, the definite molecular mechanisms of MIEN1 in colon cancer progression remain to be completely elucidated. In the present study, bioinformatics prediction showed that miR-136 could be an upstream regulator of MIEN1; a luciferase assay and Western blot assay revealed that miR-136 negatively regulates MIEN1 expression via directly targeting its 3'-untranslated region sequence. Moreover, a functional assay using wound healing and transwell invasion showed that overexpressed miR-136 inhibited cell migration and invasion, and overexpression of MIEN1 partly rescued the above-mentioned effects of miR-136 in colon cancer cells. Additionally, a clinical sample assay showed that miR-136 expression was generally downregulated in colon cancer tissue, which was inversely correlated with MIEN1 expression. Furthermore, we found that miR-136 suppressed the Akt/NF-κB signaling pathway and epithelial-to-mesenchymal transition in colon cancer. These results suggest that miR-136, as a tumor suppressor, acts in tumor metastasis by suppressing MIEN1 expression in colon cancer, providing a novel target for the treatment of colon cancer. Keywords: colon cancer, miR-136, MIEN1, migration, invasion

  20. Isolation and propagation of colon cancer stem cells

    NARCIS (Netherlands)

    Prasetyanti, Pramudita R.; Zimberlin, Cheryl; de Sousa E Melo, Felipe; Medema, Jan Paul

    2013-01-01

    The design of tissue culture conditions that faithfully reproduce the characteristics of cells in their native environment remains one of the main challenges of cancer stem cell (CSC) biology. Here we describe a detailed methodology for the isolation and expansion of both human colon CSCs and mouse