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Sample records for sw480 colorectal cancer

  1. Anti-inflammatory effect of lycopene in SW480 human colorectal cancer cells.

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    Cha, Jae Hoon; Kim, Woo Kyoung; Ha, Ae Wha; Kim, Myung Hwan; Chang, Moon Jeong

    2017-04-01

    Although the antioxidative effects of lycopene are generally known, the molecular mechanisms underlying the anti-inflammatory properties of lycopene are not fully elucidated. This study aimed to examine the role and mechanism of lycopene as an inhibitor of inflammation. Lipopolysaccharide (LPS)-stimulated SW 480 human colorectal cancer cells were treated with 0, 10, 20, and 30 µM lycopene. The MTT assay was performed to determine the effects of lycopene on cell proliferation. Western blotting was performed to observe the expression of inflammation-related proteins, including nuclear factor-kappa B (NF-κB), inhibitor kappa B (IκB), mitogen-activated protein kinase (MAPK), extracellular signal-related kinase (ERK), c-jun NH2-terminal kinase (JNK), and p38 (p38 MAP kinase). Real-time polymerase chain reaction was performed to investigate the mRNA expression of tumor necrosis factor α (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Concentrations of nitric oxide (NO) and prostaglandin E2 (PGE2) were determined via enzyme-linked immunosorbent assays. In cells treated with lycopene and LPS, the mRNA expression of TNF-α, IL-1β, IL-6, iNOS, and COX-2 were decreased significantly in a dose-dependent manner (P lycopene concentration (P lycopene concertation (P Lycopene restrains NF-κB and JNK activation, which causes inflammation, and suppresses the expression of TNF-α, IL-1β, IL-6, COX-2, and iNOS in SW480 human colorectal cancer cells.

  2. Anti-cancer effect and the underlying mechanisms of gypenosides on human colorectal cancer SW-480 cells.

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    Han Yan

    Full Text Available BACKGROUND: Gypenosides (Gyp, the main components from Gynostemma pentaphyllum Makino, are widely used in traditional Chinese medicine. The present study aimed to investigate the anti-cancer effect and the underlying mechanisms of Gyp on human colorectal cancer cells SW-480. MATERIALS AND METHODS: The inhibitory effect of Gyp on SW-480 cells was evaluated by MTT assay. Apoptotic cell death was detected by nuclear Hoechst 33342 staining and DNA fragmentation analysis. Apoptosis was analyzed using Annexin V-PE/7-amino-actinomycin D staining. Cell membrane integrity was evaluated with flow cytometry following PI staining. Changes of mitochondrial membrane potential (Δψm were detected through flow cytometry analysis of rhodamine 123 (Rh123. The role of reactive oxygen species (ROS in Gyp induced cell death was investigated by intracellular ROS generation and general ROS scavenger. Wound-healing assay was carried out to investigate Gyp-inhibited migration of SW-480 cells in vitro. Additionally, the alterations in F-actin microfilaments were analyzed by FITC-labeled phalloidin toxin staining and the morphological changes were evaluated under scanning electron microscope (SEM. RESULTS: After the Gyp treatment, the plasma membrane permeability of SW-480 cell was increased, Δψm was decreased significantly, the level of intracellular ROS level was increased, DNA fragmentation and apoptotic morphology were observed. Cells treated with Gyp exert serious microfilament network collapse as well as the significant decrease in the number of microvilli. Gyp induced the changes of cell viability, cell migration, intracellular ROS generation and nuclear morphology were alleviated obviously by NAC. CONCLUSION: The results in this study implied that ROS play an important role in Gyp induced cell toxicity and apoptosis, and the mitochondria damage may be upstream of ROS generation post Gyp treatment. The findings of the present study provide new evidences for anti

  3. Investigating migration inhibition and apoptotic effects of Fomitopsis pinicola chloroform extract on human colorectal cancer SW-480 cells.

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    Yaqin Wang

    Full Text Available BACKGROUND: Fomitopsis pinicola (Sw. Ex Fr.m Karst (FPK which belongs to the Basidiomycota fungal class is one of the most popular medical fungi in China. It has been used for many diseases: cancer, heart diseases, diabetes and so on. However, little study on the pro-apoptotic effect and migration inhibition of FPK chloroform extract (FPKc has been reported and the possible involved mechanism has not been illuminated. METHODOLOGY/PRINCIPAL FINDINGS: Chemical analysis was performed by HPLC which showed ergosterol (ES concentration was 105 µg/mg. MTT assay revealed that FPKc could selectively inhibit SW-480 cells viability with the IC50 of 190.28 µg/ml. Wound healing and transwell assay indicated that FPKc could inhibit the migration of SW-480 cells obviously, FPKc could also dramatically decreased the matrix metalloproteinases-2, 9 (MMP-2 and MMP-9 expression. Annexin V-FITC/PI staining, nuclear Hoechst 33342 staining and DNA fragmentation analysis revealed that FPKc and ES could induce SW-480 cells apoptosis. The apoptosis process closely involved in ROS accumulation and depletion of GSH, activation of caspase 3, poly (ADP-ribose polymerase (PARP degradation. FPKc could also up-regulate P53 expression and thus lead to G1 phase arrest. When SW-480 cells were pretreated with N-acetylcysteine (NAC, the ROS generation, cell viability and apoptotic ratio were partially declined, which indicated that ROS was vertical in the pro-apoptosis process induced by FPKc. Moreover, in the whole process, ES which has been previously found in FPKc had the similar effect to FPKc. Thus we could conclude that ES, as one of the highest abundant components in FPKc, might also be one of the active constituents. CONCLUSION/SIGNIFICANCE: FPKc could inhibit the migration of SW-480 cells, induce SW-480 cells G1 phase arrest and cause ROS-mediated apoptosis effect. And ES might be one of the effective constituents in the whole process.

  4. Morin Inhibits Proliferation of SW480 Colorectal Cancer Cells by Inducing Apoptosis Mediated by Reactive Oxygen Species Formation and Uncoupling of Warburg Effect

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    Thomas Sithara

    2017-09-01

    Full Text Available The study under investigation focuses on in vitro antiproliferative efficacy of the flavonoid morin and the mechanisms by which it inhibits the growth of colon cancer using SW480 colon cancer cells with emphasis on Warburg effect. It was found that the cell proliferation was significantly inhibited by morin in a dose and time dependent manner. Morin induced apoptosis that was correlated with increased levels of reactive oxygen species formation and loss of mitochondrial membrane potential of the cells. In addition, an increase in cleaved PARP, cleaved caspase 3, cleaved caspase 8, cleaved caspase 9 and Bax as well as a decrease in Bcl 2 was observed, indicating morin is inducing both intrinsic as well as extrinsic pathway of apoptosis. This was further confirmed by using downstream caspase 3 inhibitor which indicated that caspase 3 inhibition reduces morin induced cell death. Moreover, the impact of morin on over all energy status when determined in terms of total cellular ATP level showed a decline with low level of glucose uptake and Glut1 expression. The results indicate that morin exerts antiproliferative activity by inducing apoptosis and by reducing Warburg effect in the evaluated cell lines and provide preliminary evidence for its anticancer activity.

  5. 5-Geranyloxy-7-methoxycoumarin inhibits colon cancer (SW480) cells growth by inducing apoptosis.

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    Patil, Jaiprakash R; Jayaprakasha, Guddadarangavvanahally K; Kim, Jinhee; Murthy, Kotamballi N Chidambara; Chetti, Mahadev B; Nam, Sang-Yong; Patil, Bhimanagouda S

    2013-03-01

    For the first time, three coumarins were isolated from the hexane extract of limes (Citrus aurantifolia) and purified by flash chromatography. The structures were identified by NMR (1D, 2D) and mass spectral analyses as 5-geranyloxy-7-methoxycoumarin, limettin, and isopimpinellin. These compounds inhibited human colon cancer (SW-480) cell proliferation, with 5-geranyloxy-7-methoxycoumarin showing the highest inhibition activity (67 %) at 25 µM. Suppression of SW480 cell proliferation by 5-geranyloxy-7-methoxycoumarin was associated with induction of apoptosis, as evidenced by annexin V staining and DNA fragmentation. In addition, 5-geranyloxy-7-methoxycoumarin arrested cells at the G0/G1 phase, and induction of apoptosis was demonstrated through the activation of tumour suppressor gene p53, caspase8/3, regulation of Bcl2, and inhibition of p38 MAPK phosphorylation. These findings suggest that 5-geranyloxy-7-methoxycoumarin has potential as a cancer preventive agent. Georg Thieme Verlag KG Stuttgart · New York.

  6. Effects of Lidocaine on HT-29 and SW480 Colon Cancer CellsIn Vitro.

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    Bundscherer, Anika C; Malsy, Manuela; Bitzinger, Diane I; Wiese, Christoph H R; Gruber, Michael A; Graf, Bernhard M

    2017-04-01

    Evidence is growing that the risk of cancer dissemination may be enhanced during the perioperative period. Whether particular anesthetic techniques influence oncological outcome is still under discussion. For pain management, lidocaine can be administered perioperatively by intravenous, intraperitoneal or epidural infusion. Here we investigated the effect of lidocaine on colon carcinoma cell lines (HT-29 and SW480) in vitro. ELISA BrdU (Roche) for cell proliferation and FITC Annexin V detection kit (BD Pharming) for apoptosis analysis were applied. Cell-cycle profiles were investigated by flow cytometry. Cell-cycle arrest was induced in both cell lines by 1000 μM lidocaine, while no inhibition of cell proliferation was detected. Apoptosis decreased in SW480 but not in HT-29 cells. Lidocaine induces cell-cycle arrest in both colon carcinoma cell lines in vitro. The effective drug concentration can be obtained by local infiltration. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  7. Characterization of side population cells isolated from the colon cancer cell line SW480.

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    Xiong, Binghong; Ma, Li; Hu, Xiang; Zhang, Caiquan; Cheng, Yong

    2014-09-01

    Side population (SP) cells may play a crucial role in tumorigenesis and the recurrence of cancer. Many types of cell lines and tissues have demonstrated the presence of SP cells, including colon cancer cell lines. This study aimed to identify cancer stem cells (CSCs) in the SP of the colon cancer cell line SW480. SP cells were isolated by fluorescence-activated cell sorting (FACS), followed by serum-free medium (SFM) culture. The self-renewal, differentiated progeny, clone formation, proliferation, invasion ability, cell cycle, chemosensitivity and tumorigenic properties in SP and non-SP (NSP) cells were investigated through in vitro culture and in vivo serial transplantation. The expression profiles of ATP-binding cassette (ABC) protein transporters and stem cell-related genes were examined by RT-PCR and western blot analysis. The human colon cancer cell lines SW480, Lovo and HCT116 contain 1.1 ± 0.10, 0.93 ± 0.11 and 1.33 ± 0.05% SP cells, respectively. Flow cytometry analysis revealed that SP cells could differentiate into SP and NSP cells. SP cells had a higher proliferation potency and CFE than NSP cells. Compared to NSP cells, SP cells were also more resistant to CDDP and 5-FU, and were more invasive and displayed increased tumorigenic ability. Moreover, SP cells showed higher mRNA and protein expression of ABCG2, MDR1, OCT-4, NANOG, SOX-2, CD44 and CD133. SP cells isolated from human colon cancer cell lines harbor CSC properties that may be related to the invasive potential and therapeutic resistance of colon cancer.

  8. Knockdown of β-catenin by siRNA influences proliferation, apoptosis and invasion of the colon cancer cell line SW480

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    Li, Kui; Zhou, Zhong-Yin; JI, PAN-PAN; Luo,He-Sheng

    2016-01-01

    The aim of the present study was to explore the effect of knocking down the expression of β-catenin by small interference (si)RNA on the activity of the Wnt/β-catenin signaling pathway, and the proliferation, apoptosis and invasion abilities of the human colon cancer cell line SW480. For that purpose, double-stranded siRNA targeting β-catenin (β-catenin-siRNA) was synthesized and transfected into SW480 cells. Reverse transcription-polymerase chain reaction (RT-PCR) and western blotting were u...

  9. Pro-apoptotic activities of polyphenolics from açai (Euterpe oleracea Martius) in human SW-480 colon cancer cells.

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    Dias, Manoela Maciel dos Santos; Noratto, Giuliana; Martino, Hercia Stampini Duarte; Arbizu, Shirley; Peluzio, Maria do Carmo Gouveia; Talcott, Stephen; Ramos, Afonso Mota; Mertens-Talcott, Susanne U

    2014-01-01

    This study aimed to evaluate the cell growth inhibition activity of açai (Euterpe oleracea Mart.) polyphenolic extract against colon cancer HT-29 and SW-480 cells and the nonmalignant CCD-18Co colon fibroblast cells. Results showed that açai polyphenolic extract (5-20 mg/L) inhibited preferentially the growth of SW-480 cells with no toxicity in CCD-18Co cells, and this was accompanied by reduction of H2O2-induced reactive oxygen species (ROS) generation. The mechanisms involved in SW-480 cell growth-inhibition by açai polyphenolic extract included the downregulation of NF-κB proinflammatory transcription factor and the nuclear factor-kappa B targets intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Furthermore, prooncogenic specificity proteins (Sp) were downregulated as well as Sp-targets Bcl-2, vascular endothelial growth factor, and survivin. This was accompanied by activation of mitochondrial proapoptotic pathway involving increase of cytochrome c, cleavage of caspase-3, and decrease of PARP-1. Results strongly suggest that açai polyphenolic extract has antiinflammatory and cytotoxic activities in colon cancer cells and can be effective as natural colon cancer chemopreventive agents.

  10. Protein-bound polysaccharide from Phellinus linteus inhibits tumor growth, invasion, and angiogenesis and alters Wnt/β-catenin in SW480 human colon cancer cells

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    Park Hae-Duck

    2011-07-01

    Full Text Available Abstract Background Polysaccharides extracted from the Phellinus linteus (PL mushroom are known to possess anti-tumor effects. However, the molecular mechanisms responsible for the anti-tumor properties of PL remain to be explored. Experiments were carried out to unravel the anticancer effects of PL. Methods The anti-cancer effects of PL were examined in SW480 colon cancer cells by evaluating cell proliferation, invasion and matrix metallo-proteinase (MMP activity. The anti-angiogenic effects of PL were examined by assessing human umbilical vein endothelial cell (HUVEC proliferation and capillary tube formation. The in vivo effect of PL was evaluated in an athymic nude mouse SW480 tumor engraft model. Results PL (125-1000 μg/mL significantly inhibited cell proliferation and decreased β-catenin expression in SW480 cells. Expression of cyclin D1, one of the downstream-regulated genes of β-catenin, and T-cell factor/lymphocyte enhancer binding factor (TCF/LEF transcription activity were also significantly reduced by PL treatment. PL inhibited in vitro invasion and motility as well as the activity of MMP-9. In addition, PL treatment inhibited HUVEC proliferation and capillary tube formation. Tumor growth of SW480 cells implanted into nude mice was significantly decreased as a consequence of PL treatment, and tumor tissues from treated animals showed an increase in the apoptotic index and a decrease in β-catenin expression. Moreover, the proliferation index and microvessel density were significantly decreased. Conclusions These data suggest that PL suppresses tumor growth, invasion, and angiogenesis through the inhibition of Wnt/β-catenin signaling in certain colon cancer cells.

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

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    Ai-Qun Liu

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

  12. Establishment and Analysis of Cancer Stem-Like and Non-Cancer Stem-Like Clone Cells from the Human Colon Cancer Cell Line SW480.

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    Akari Takaya

    Full Text Available Human cancer stem-like cells (CSCs/cancer-initiating cells (CICs can be isolated as side population (SP cells, aldehyde dehydrogenase high (ALDHhigh cells or cell surface marker-positive cells including CD44+ cells and CD133+ cells. CSCs/CICs and non-CSCs/CICs are unstable in in vitro culture, and CSCs/CICs can differentiate into non-CSCs/CICs and some non-CSCs/CICs can dedifferentiate into CSCs/CICs. Therefore, experiments using a large amount of CSCs/CICs are technically very difficult. In this study, we isolated single cell clones from SP cells and main population (MP cells derived from the human colon cancer cell line SW480. SP analysis revealed that SP clone cells had relatively high percentages of SP cells, whereas MP clone cells showed very few SP cells, and the phenotypes were sustainable for more than 2 months of in vitro culture. Xenograft transplantation revealed that SP clone cells have higher tumor-initiating ability than that of MP clone cells and SP clone cell showed higher chemo-resistance compared with MP clone cells. These results indicate that SP clone cells derived from SW480 cells are enriched with CSCs/CICs, whereas MP clone cells are pure non-CSCs/CICs. SP clone cells and MP clone cells are a very stable in vitro CSC/CIC-enriched and non-CSC/CIC model for further analysis.

  13. MicroRNA-184 inhibits proliferation and promotes apoptosis of human colon cancer SW480 and HCT116 cells by downregulating C-MYC and BCL-2.

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    Wang, Yong-Bing; Zhao, Xiao-Hui; Li, Gang; Zheng, Jun-Hua; Qiu, Wei

    2018-02-01

    This study aimed to investigate the effects of microRNA-184 (miR-184) on the proliferation and apoptosis of human colon cancer cells through the regulation of C-MYC and BCL-2. Human colon cancer tissues were selected as case group, and adjacent normal tissues were as control group. Human colon cancer SW480 and HCT116 cells were allocated into blank, miR-184 mimic negative control (mimic-NC), miR-184 inhibitor NC (inhibitor-NC), miR-184 mimic, and miR-184 inhibitor groups. Flow cytometry, Annexin V/PI and MTT assay were used to examine the cell cycle, apoptosis and viability. The expressions of C-MYC, BCL-2 and miR-184 were detected via immunohistochemistry, Western blotting and reverse transcription quantitative polymerase chain reaction (RT-qPCR). C-MYC and BCL-2 were direct targets to miR-184. The growth of colon cancer cells in the miR-184 mimic group was inhibited and exhibited an increase in apoptosis. Cell growth in the miR-184 mimic group was increased in addition to the inhibition of apoptosis. Compared with miR-184 mimic group, the expressions of C-MYC and BCL-2 in miR-184 inhibitor group were increased. The expressions of C-MYC and BCL-2 in colon cancer tissues exhibited high levels of expression, while miR-184 displayed relatively low levels in comparison to the adjacent normal tissues. An association was detected regarding the expressions of miR-184, C-MYC and BCL-2 with the differentiation, invasion depth and lymph node metastasis. MiR-184 expression was negatively related to C-MYC and BCL-2 expressions. Our study suggested that miR-184 could inhibit proliferation and promote apoptosis of colon cancer cells by down-regulating expressions of C-MYC and BCL-2. © 2017 Wiley Periodicals, Inc.

  14. Study of morphological and mechanical features of multinuclear and mononuclear SW480 cells by atomic force microscopy.

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    Liu, Jinyun; Qu, Yingmin; Wang, Guoliang; Wang, Xinyue; Zhang, Wenxiao; Li, Jingmei; Wang, Zuobin; Li, Dayou; Jiang, Jinlan

    2017-10-09

    This article studies the morphological and mechanical features of multinuclear and mononuclear SW480 colon cancer cells by atomic force microscopy to understand their drug-resistance. The SW480 cells were incubated with the fullerenol concentrations of 1 mg/ml and 2 mg/ml. Morphological and mechanical features including the height, length, width, roughness, adhesion force and Young's modulus of three multinuclear cell groups and three mononuclear cell groups were imaged and analyzed. It was observed that the features of multinuclear cancer cells and mononuclear cancer cells were significantly different after the treatment with fullerenol. The experiment results indicated that the mononuclear SW480 cells were more sensitive to fullerenol than the multinuclear SW480 cells, and the multinuclear SW480 cells exhibited a stronger drug-resistance than the mononuclear SW480 cells. This work provides a guideline for the treatments of multinuclear and mononuclear cancer cells with drugs. © 2017 Wiley Periodicals, Inc.

  15. Akt and phospholipase Cγ are involved in the regulation of growth and migration of MDA-MB-468 breast cancer and SW480 colon cancer cells when cultured with diabetogenic levels of glucose and insulin

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    Tomas Nicola M

    2012-07-01

    Full Text Available Abstract Background Epidemiological studies revealed a strong correlation between the metabolic syndrome/diabetes mellitus type 2 (DM2 and higher incidence and faster progression of breast and colon cancer. However, the underlying molecular mechanisms are widely unknown. Akt and phospholipase Cγ (PLCγ are involved in tyrosine kinase signaling and promote tumor cell growth and migration. Therefore, we examined regulatory functions and expression of Akt and PLCγ in a simplified in vitro diabetogenic model. Findings Protein expression was determined by western blot analysis in MDA-MB-468 breast cancer and SW480 colon cancer cells previously cultured under physiologic (5.5 mM and diabetogenic (11 mM glucose concentrations (without and with 100 ng/ml insulin. We studied the culture effects on proliferation and migration of these cells, especially after inhibiting Akt and PLCγ. We found that Akt expression was up-regulated with high glucose and insulin in both cell lines, whereas PLCγ expression was enhanced in colon cancer cells only. High levels of glucose and insulin increased cell proliferation and migration in both cell lines in vitro, mediated by Akt and PLCγ, as shown through the specific pharmacological inhibitors A6730 and U73122. Conclusions Our molecular data explain glucose- and insulin-induced changes in a cancer cell and help to understand what might trigger tumor cell proliferation and migration in DM2 patients, too.

  16. Expression of the proto-oncogene Pokemon in colorectal cancer--inhibitory effects of an siRNA.

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    Zhao, Gan-Ting; Yang, Li-Juan; Li, Xi-Xia; Cui, Hui-Lin; Guo, Rui

    2013-01-01

    This study aimed to investigate expression of the proto-oncogene POK erythroid myeloid ontogenic factor (Pokemon) in colorectal cancer (CRC), and assess inhibitory effects of a small interference RNA (siRNA) expression vector in SW480 and SW620 cells. Semi-quantitative reverse transcription-polymerase chain reaction (PCR) and immunohistochemistry were performed to determine mRNA and protein expression levels of Pokemon in CRC tissues. Indirect immunofluorescence staining was applied to investigate the location of Pokemon in SW480 and SW620 cells. The siRNA expression vectors that were constructed to express a short hairpin RNA against Pokemon were transfected to the SW480 and SW620 cells with a liposome. Expression levels of Pokemon mRNA and protein were examined by real-time quantitative-fluorescent PCR and western blot analysis. The effects of Pokemon silencing on proliferation of SW480 and SW620 cells were evaluated with reference to growth curves with MTT assays. The mRNA expression level of Pokemon in tumor tissues (0.845 ± 0.344) was significantly higher than that in adjacent tumor specimens (0.321 ± 0.197). The positive expression ratio of Pokemon protein in CRC (87.0%) was significantly higher than that in the adjacent tissues (19.6%). Strong fluorescence staining of Pokemon protein was observed in the cytoplasm of the SW480 and SW620 cells. The inhibition ratios of Pokemon mRNA and protein in the SW480 cells were 83.1% and 73.5% at 48 and 72 h, respectively, compared with those of the negative control cells with the siRNA. In the SW620 cells, the inhibition ratios of Pokemon mRNA and protein were 76.3% and 68.7% at 48 and 72 h, respectively. MTT showed that Pokemon gene silencing inhibited the proliferation of SW480 and SW620 cells. Overexpression of Pokemon in CRC may have a function in carcinogenesis and progression. siRNA expression vectors could effectively inhibit mRNA and protein expression of Pokemon in SW480 and SW620 cells, thereby reducing

  17. Colorectal Cancer

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

  18. Anti-Cancer Effects of Protein Extracts from Calvatia lilacina, Pleurotus ostreatus and Volvariella volvacea

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    Jin-Yi Wu

    2011-01-01

    Full Text Available Calvatia lilacina (CL, Pleurotus ostreatus (PO and Volvariella volvacea (VV are widely distributed worldwide and commonly eaten as mushrooms. In this study, cell viabilities were evaluated for a human colorectal adenocarcinoma cell line (SW480 cells and a human monocytic leukemia cell line (THP-1 cells. Apoptotic mechanisms induced by the protein extracts of PO and VV were evaluated for SW480 cells. The viabilities of THP-1 and SW480 cells decreased in a concentration-dependent manner after 24 h of treatment with the protein extracts of CL, PO or VV. Apoptosis analysis revealed that the percentage of SW480 cells in the SubG1 phase (a marker of apoptosis was increased upon PO and VV protein-extract treatments, indicating that oligonucleosomal DNA fragmentation existed concomitantly with cellular death. The PO and VV protein extracts induced reactive oxygen species (ROS production, glutathione (GSH depletion and mitochondrial transmembrane potential (ΔΨm loss in SW480 cells. Pretreatment with N-acetylcysteine, GSH or cyclosporine A partially prevented the apoptosis induced by PO protein extracts, but not that induced by VV extracts, in SW480 cells. The protein extracts of CL, PO and VV exhibited therapeutic efficacy against human colorectal adenocarcinoma cells and human monocytic leukemia cells. The PO protein extracts induced apoptosis in SW480 cells partially through ROS production, GSH depletion and mitochondrial dysfunction. Therefore, the protein extracts of these mushrooms could be considered an important source of new anti-cancer drugs.

  19. Cell and nuclear enlargement of SW480 cells induced by a plant lignan, arctigenin: evaluation of cellular DNA content using fluorescence microscopy and flow cytometry.

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    Kang, Kyungsu; Lee, Hee Ju; Yoo, Ji-Hye; Jho, Eun Hye; Kim, Chul Young; Kim, Minkyun; Nho, Chu Won

    2011-08-01

    Arctigenin is a natural plant lignan previously shown to induce G(2)/M arrest in SW480 human colon cancer cells as well as AGS human gastric cancer cells, suggesting its use as a possible cancer chemopreventive agent. Changes in cell and nuclear size often correlate with the functionality of cancer-treating agents. Here, we report that arctigenin induces cell and nuclear enlargement of SW480 cells. Arctigenin clearly induced the formation of giant nuclear shapes in SW480, as demonstrated by fluorescence microscopic observation and quantitative determination of nuclear size. Cell and nuclear size were further assessed by flow cytometric analysis of light scattering and fluorescence pulse width after propidium iodide staining. FSC-H and FL2-W values (parameters referring to cell and nuclear size, respectively) significantly increased after arctigenin treatment; the mean values of FSC-H and FL2-W in arctigenin-treated SW480 cells were 572.6 and 275.1, respectively, whereas those of control cells were 482.0 and 220.7, respectively. Our approach may provide insights into the mechanism behind phytochemical-induced cell and nuclear enlargement as well as functional studies on cancer-treating agents.

  20. Different Schedule-Dependent Effects of Epigenetic Modifiers on Cytotoxicity by Anticancer Drugs in Colorectal Cancer Cells.

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    Hosokawa, Mika; Tanaka, Shota; Ueda, Kumiko; Iwakawa, Seigo

    2017-12-01

    Limited information is currently available on how to apply epigenetic modifiers to current colorectal cancer (CRC) chemotherapy. The purpose of this study is to clarify the schedule-dependent effects of combined treatment with conventional anticancer drugs and epigenetic modifiers in human CRC cells. Cytotoxicity in 4 CRC cell lines (SW480, HT29, SW48, and HCT116) was measured using the WST-8 assay. As epigenetic modifiers, 3 DNA methyltransferase (DNMT) inhibitors such as decitabine (DAC), azacytidine (AC), and zebularine (Zeb), and 3 histone deacetylase (HDAC) inhibitors including trichostatin A (TSA), suberoylanilide hydroxamic acid (SAHA), and valproic acid (VPA) were used. Combination effects were analyzed by the isobologram method. SW480 cells showed the lowest sensitivity to the anticancer drugs 5-fluorouracil, SN-38 (the active form of irinotecan), and oxaliplatin. In SW480 cells, epigenetic modifiers other than VPA showed the most significant synergistic effects when used before anticancer drugs, while VPA showed synergistic effects in co- or post-treatment. In the 3 other CRC cells, synergistic effects were less frequent and weaker. The dose of anticancer drugs may be reduced by combining epigenetic modifiers in SW480 cells, which are less sensitive to anticancer drugs, unlike the more sensitive HT29, SW48, and HCT116 cell lines. These results provide useful information for understanding how to incorporate epigenetic modifiers into current CRC chemotherapy.

  1. Antisense gene therapy using anti-k-ras and antitelomerase oligonucleotides in colorectal cancer Eficacia de la terapia génica antisentido utilizando oligonucleótidos anti K-ras y antitelomerasa en cáncer colorrectal

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    S. Lledó; Alfonso, R; S. F. Aliño

    2005-01-01

    Aim: to test the efficacy of anti-k-ras and antitelomerase oligonucleotides for disabling colorectal cancer cell growth. Material and methods: an established human colorectal cancer cell line (SW 480, ATTC®) was used. Oligodeoxiribonucleotides (ODNs) have a phosphorotioate modification to ensure intracellular intake. We used an antitelomerase ODN (Telp5) and two anti-k-ras ODNs (AS-KRAS and ISIS). AS-KRAS is designed to join the k-ras oncogene's exon 1. ISIS links to the terminal transcriptio...

  2. Complex Behavior of ALDH1A1 and IGFBP1 in Liver Metastasis from a Colorectal Cancer.

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    Jin Cheon Kim

    Full Text Available Using our data set (GSE50760 previously established by RNA sequencing, the present study aimed to identify upregulated genes associated with colorectal cancer (CRC liver metastasis (CLM and verify their biological behavior. The potential roles of candidate genes in tumors were assessed using cell proliferation and invasion assays. Tissue samples were collected from 18 CRC patients with synchronous CLM and two CRC cell lines (SW480 and SW620 were used for transfection and cloning. The roles of the genes identified in CLM were verified using immunohistochemistry in 48 nude mice after intrasplenic transplantation of CRC cells. mRNA and protein expression was determined by quantitative real-time reverse transcription polymerase chain reaction and western blot, respectively. Nine genes were initially selected according to the relevance of their molecular function and biological process and, finally, ALDH1A1 and IGFBP1 were chosen based on differential mRNA expression and a positive correlation with protein expression. The overexpression of ALDH1A1 and IGFBP1 significantly and time-dependently decreased cell proliferation (p ≤ 0.001-0.003 and suppressed invasiveness by ≥3-fold over control cells (p < 0.001 in the SW480 cell line, whereas they had a slight effect on reducing SW620 cell proliferation. The protein expression levels of E-cadherin, N-cadherin, claudin-1, and vimentin were significantly higher in CLM than in primary tumor tissues (p < 0.05. However, the cadherin switch, namely, N-cadherin overexpression with reduced E-cadherin expression, was not observed in CLM tissues and transfected CRC cells. Irrespective of reduced proliferation and invasion found on in vitro cell assays, persistent overexpression of β-catenin, vimentin, and ZO-1 in IGFBP1-overexpressing SW480 cells possibly contributed to CLM development in mice implanted with IGFBP1-overexpressing SW480 cells (CLM occurrences: SW480/IGFBP1-transfected mice vs. SW480/vector- and

  3. Effects of krill oil on serum lipids of hyperlipidemic rats and human SW480 cells.

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    Zhu, Jia-Jin; Shi, Jia-Hui; Qian, Wen-Bin; Cai, Zhen-Zhen; Li, Duo

    2008-08-29

    Cardiovascular disease (CVD) and colon cancer incidence are known to be closely related to dietary factors. This article evaluated effects of krill oil (KO) on serum lipids of hyperlipidemia rats and human colon cancer cells (SW480). Serum lipids of rats fed with high fat diet (HFD) and different doses of KO were measured by automatic analyzer. Effect of KO on viability of cells was determined by methyl thiazolyl tetrazolium (MTT) assay. Except for higher dose group, body weights decreased significantly. Total cholesterol (TC), LDL-cholesterol (LDL-C) of all dose groups, Triglycerides (TG) of low and mid dose groups descended significantly, while there were no significant differences of HDL-cholesterol (HDL-C), compared with control group. Treatment of colon cancer cells with KO also resulted in time-dependent inhibition of cell growth. Our findings indicated that the consumption of KO may provide benefits to control serum lipid levels in certain diseases and inhibit growth of colon cancer cells. Therefore, KO may be a good candidate for development as a functional food and nutraceutical.

  4. Effects of Krill Oil on serum lipids of hyperlipidemic rats and human SW480 cells

    Directory of Open Access Journals (Sweden)

    Qian Wen-Bin

    2008-08-01

    Full Text Available Abstract Background Cardiovascular disease (CVD and colon cancer incidence are known to be closely related to dietary factors. This article evaluated effects of krill oil (KO on serum lipids of hyperlipidemia rats and human colon cancer cells (SW480. Serum lipids of rats fed with high fat diet (HFD and different doses of KO were measured by automatic analyzer. Effect of KO on viability of cells was determined by methyl thiazolyl tetrazolium (MTT assay. Results Except for higher dose group, body weights decreased significantly. Total cholesterol (TC, LDL-cholesterol (LDL-C of all dose groups, Triglycerides (TG of low and mid dose groups descended significantly, while there were no significant differences of HDL-cholesterol (HDL-C, compared with control group. Treatment of colon cancer cells with KO also resulted in time-dependent inhibition of cell growth. Conclusion Our findings indicated that the consumption of KO may provide benefits to control serum lipid levels in certain diseases and inhibit growth of colon cancer cells. Therefore, KO may be a good candidate for development as a functional food and nutraceutical.

  5. Colorectal Cancer Screening

    Science.gov (United States)

    ... Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ...

  6. Colorectal Cancer

    Science.gov (United States)

    ... detected by optical colonoscopy. Virtual colonoscopy uses virtual reality technology to produce three-dimensional images of the ... that if current trends in reducing risk factors, increased screening, and better treatment persist, colorectal cancer mortality ...

  7. Sp1 upregulates expression of TRF2 and TRF2 inhibition reduces tumorigenesis in human colorectal carcinoma cells.

    Science.gov (United States)

    Dong, Wenjie; Shen, Ruizhe; Wang, Qi; Gao, Yabo; Qi, Xiaoguang; Jiang, He; Yao, Jingjing; Lin, Xiaolin; Wu, Yunlin; Wang, Lifu

    2009-11-01

    Telomere repeat binding factor 2 (TRF2) plays a key role in the protective activity of telomere and is overexpression in several kinds of solid cancer cells. However, the role of overexpressed TRF2 in colorectal carcinoma remains unclear. The aim of this study was to determine the expression of TRF2, address the mechanism of TRF2 overexpression in human colorectal carcinoma. In present study, we examined the expression of TRF2 in colorectal cancer tissues from 39 patients, peritumoral normal tissues from 21 patients, and colon carcinoma SW480 cell line by quantitative PCR, immunohistochemistry and western blot. After siRNA silencing TRF2 expression in SW480, tumorigenesis of TRF2 was tested by cell proliferation, soft agar assay, cytofluorimetric analysis and cytogenetic analysis. To discover transcription factor that mediated TRF2 expression, Chromatin Immunoprecipitation (Chip) Assay and Electrophoretic mobility shift assays (EMSA) were employed. Overexpression of TRF2 protein was detected in SW480 cells and 19 of 39 colorectal carcinoma tissues (49%), no overexpression was observed in 21 of 21 adjacent peritumoral normal colorectal tissues. After siRNA silencing TRF2 expression, the proliferation and colony formation of SW480 cells were significantly inhibited. Defective TRF2 induced apoptosis and increased chromosomal instability in SW480 cells, in which there were more end-to-end fusions and ring chromosomes. Chip assay and EMSA showed that transcription factor Sp1 is involved in upregulation of TRF2. These results indicate that TRF2 is overexpressed in colorectal carcinoma, Sp1 upregulates TRF2 expression, TRF2 inhibition reduces tumorigenesis of colorectal cancer, which suggests that TRF2 and SP1 may become new targets for the development of anti-cancer therapy in colorectal carcinoma.

  8. MicroRNA-203-mediated posttranscriptional deregulation of CPEB4 contributes to colorectal cancer progression

    Energy Technology Data Exchange (ETDEWEB)

    Zhong, Xiaohua; Xiao, Yipin; Chen, Chao, E-mail: chenchaopw@126.com; Wei, Xiuwen; Hu, Chen; Ling, Xukun; Liu, Xinbin

    2015-10-16

    Elevated cytoplasmic polyadenylation element-binding 4 (CPEB4) is aberrantly expressed in several malignant cancers. However, its expression pattern, clinical significance, and biological function in colorectal cancer are still unknown. In this study, we demonstrated that CPEB4 is abundantly overexpressed in colorectal cancers and has the potential to be used for predicting clinical outcomes of colorectal cancer patients. We suppressed CPEB4 expression by small interfering RNA (siRNA) in SW480 and LOVO cells to clarify the role of CPEB4 on the cell apoptosis and proliferation in vitro. Further study revealed that knockdown of CPEB4 decreased the expression of anti-apoptotic protein B-cell lymphoma-extra large (Bcl-XL), but enhanced the expression of B-cell lymphoma-2-associated X (Bax). In addition, we indicated that CPEB4 is a novel target of miR-203, a tumor suppressive microRNA. Notably, restoration of CPEB4 in SW480 cells inhibited miR-203-induced apoptosis signaling pathway, which in turn enhanced cell proliferation and suppressed cell apoptosis. Taken together, our findings imply that posttranscriptional deregulation of CPEB4 contributes to the inhibited cell proliferation and the enhanced cell apoptosis in colorectal cancer, and directly targeting CPEB4 by miR-203 might be a novel strategy in colorectal cancer treatment. - Highlights: • CPEB4 is aberrantly expressed in human colorectal cancers. • Knockdown of CPEB4 inhibited colorectal cancer cell proliferation and enhanced apoptosis. • CPEB4 is a direct target of miR-203 and inversely correlates with miR-203 expression. • miR-203 inhibited cell growth and enhanced cell apoptosis in CPEB4 dependent manner. • miR-203 is an upstream regulator of the CPEB4-induced apoptosis pathway.

  9. Phosphatidylinositol 5-phosphate 4-kinase type II beta is required for vitamin D receptor-dependent E-cadherin expression in SW480 cells

    Energy Technology Data Exchange (ETDEWEB)

    Kouchi, Zen, E-mail: zkouchi@toyaku.ac.jp [Laboratory of Genome and Biosignals, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-city, Tokyo 192-0392 (Japan); Fujiwara, Yuki [Laboratory of Genome and Biosignals, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-city, Tokyo 192-0392 (Japan); Yamaguchi, Hideki [Division of Metastasis and Invasion Signaling, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); PRESTO, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi-city, Saitama 332-0012 (Japan); Nakamura, Yoshikazu; Fukami, Kiyoko [Laboratory of Genome and Biosignals, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-city, Tokyo 192-0392 (Japan)

    2011-05-20

    Highlights: {yields} We analyzed Phosphatidylinositol 5-phosphate kinase II{beta} (PIPKII{beta}) function in cancer. {yields} PIPKII{beta} is required for vitamin D receptor-mediated E-cadherin upregulation in SW480. {yields} PIPKII{beta} suppresses cellular motility through E-cadherin induction in SW480 cells. {yields} Nuclear PIP{sub 2} but not plasma membrane-localized PIP{sub 2} mediates E-cadherin upregulation. -- Abstract: Numerous epidemiological data indicate that vitamin D receptor (VDR) signaling induced by its ligand or active metabolite 1{alpha},25-dihydroxyvitamin D{sub 3} (1{alpha},25(OH){sub 2}D{sub 3}) has anti-cancer activity in several colon cancers. 1{alpha},25(OH){sub 2}D{sub 3} induces the epithelial differentiation of SW480 colon cancer cells expressing VDR (SW480-ADH) by upregulating E-cadherin expression; however, its precise mechanism remains unknown. We found that phosphatidylinositol-5-phosphate 4-kinase type II beta (PIPKII{beta}) but not PIPKII{alpha} is required for VDR-mediated E-cadherin induction in SW480-ADH cells. The syntenin-2 postsynaptic density protein/disc large/zona occludens (PDZ) domain and pleckstrin homology domain of phospholipase C-delta1 (PLC{delta}1 PHD) possess high affinity for phosphatidylinositol-4,5-bisphosphate (PI(4,5)P{sub 2}) mainly localized to the nucleus and plasma membrane, respectively. The expression of syntenin-2 PDZ but not PLC{delta}1 PHD inhibited 1{alpha},25(OH){sub 2}D{sub 3}-induced E-cadherin upregulation, suggesting that nuclear PI(4,5)P{sub 2} production mediates E-cadherin expression through PIPKII{beta} in a VDR-dependent manner. PIPKII{beta} is also involved in the suppression of the cell motility induced by 1{alpha},25(OH){sub 2}D{sub 3}. These results indicate that PIPKII{beta}-mediated PI(4,5)P{sub 2} signaling is important for E-cadherin upregulation and inhibition of cellular motility induced by VDR activation.

  10. Colorectal Cancer

    African Journals Online (AJOL)

    Peter Donald

    history, young age at onset and presence of other specific tumours and defects. Among these defects are ... medical advice. Only 2 (6.3%) patients completed their treatment regimen. Conclusion: The incidence of colorectal cancer is still low in our environment but treatment outcome remains poor due to late presentation.

  11. Downregulation of microRNA-498 in colorectal cancers and its cellular effects

    Energy Technology Data Exchange (ETDEWEB)

    Gopalan, Vinod; Smith, Robert A.; Lam, Alfred K.-Y., E-mail: a.lam@griffith.edu.au

    2015-01-15

    miR-498 is a non-coding RNA located intergenically in 19q13.41. Due to its predicted targeting of several genes involved in control of cellular growth, we examined the expression of miR-498 in colon cancer cell lines and a large cohort of patients with colorectal adenocarcinoma. Two colon cancer cancer cell lines (SW480 and SW48) and one normal colonic epithelial cell line (FHC) were recruited. The expression of miR-498 was tested in these cell lines by using quantitative real-time polymerase chain reaction (qRT-PCR). Tissues from 80 patients with surgical resection of colorectum (60 adenocarcinomas and 20 non-neoplastic tissues) were tested for miR-498 expression by qRT-PCR. In addition, an exogenous miR-498 (mimic) was used to detect the miRNA's effects on cell proliferation and cell cycle events in SW480 using MTT calorimetric assay and flow cytometry respectively. The colon cancer cell lines showed reduced expression of miR-498 compared to a normal colonic epithelial cell line. Mimic driven over expression of miR-498 in the SW480 cell line resulted in reduced cell proliferation and increased proportions of G2-M phase cells. In tissues, miR-498 expression was too low to be detected in all colorectal adenocarcinoma compared to non-neoplastic tissues. This suggests that the down regulation of miR-498 in colorectal cancer tissues and the direct suppressive cellular effect noted in cancer cell lines implies that miR-498 has some direct or indirect role in the pathogenesis of colorectal adenocarcinomas. - Highlights: • miR-498 is a non-coding RNA located in 19q13.41. • Colon cancer cell lines showed reduced expression of miR-498. • Mimic driven over expression of miR-498 in colon cancer cells resulted in lower cell proliferation. • miR-498 expression was down regulated in all colorectal adenocarcinoma tissues.

  12. 6 Common Cancers - Colorectal Cancer

    Science.gov (United States)

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

  13. Colorectal Cancer Prevention

    Science.gov (United States)

    ... cancer: Age Family history of colorectal cancer Personal history Inherited risk Alcohol Cigarette smoking Obesity The following protective factors decrease the risk of colorectal cancer: Physical activity Aspirin Combination hormone replacement therapy Polyp removal It is ...

  14. Chemopreventive Effects of Oplopantriol A, a Novel Compound Isolated from Oplopanax horridus, on Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Zhiyu Zhang

    2014-07-01

    Full Text Available Oplopanax horridus is a North American botanical that has received limited investigations. We previously isolated over a dozen of the constituents from O. horridus, and among them oplopantriol A (OPT A is a novel compound. In this study, we firstly evaluated the in vivo chemoprevention activities of OPT A using the xenograft colon cancer mouse model. Our data showed that this compound significantly suppressed tumor growth with dose-related effects (p < 0.01. Next, we characterized the compound’s growth inhibitory effects in human colorectal cancer cell lines HCT-116 and SW-480. With OPT A treatment, these malignant cells were significantly inhibited in both a concentration- and time-dependent manner (both p < 0.01. The IC50 was approximately 5 µM for HCT-116 and 7 µM for SW-480 cells. OPT A significantly induced apoptosis and arrested the cell cycle at the G2/M phase. From further mechanism explorations, our data showed that OPT A significantly upregulated the expression of a cluster of genes, especially the tumor necrosis factor receptor family and caspase family, suggesting that the tumor necrosis factor-related apoptotic pathway plays a key role in OPT A induced apoptosis.

  15. Risks of Colorectal Cancer Screening

    Science.gov (United States)

    ... Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ...

  16. Detection of Cytotoxic Activity of Lectin on Human Colon Adenocarcinoma (Sw480 and Epithelial Cervical Carcinoma (C33-A

    Directory of Open Access Journals (Sweden)

    Mirandeli Bautista

    2011-03-01

    Full Text Available Lectins comprise a heterogeneous class of proteins that recognize the carbohydrate moieties of glycoconjugates with high specificity. Numerous studies have shown that lectins are capable of recognizing specific carbohydrate moieties displayed by malignant cells or tissues. The present work was performed to investigate the effects of tepary bean (Phaseolus acutifolius lectins on proliferation, colony formation, and alteration of DNA synthesis of human malignant cells. Tepary bean lectin showed dose dependent  effects on the inhibition of viability as well as on colony formation in two human malignant cells lines (C33-A, Sw480; By contrast, tepary bean lectin only showed significant effects on DNA synthesis on Sw480 cells. Our results provide evidence of the anti- proliferative and cytotoxic effects of the tepary bean lectins on C33-A and Sw480 cells lines.

  17. The expression pattern of long non-coding RNA PVT1 in tumor tissues and in extracellular vesicles of colorectal cancer correlates with cancer progression.

    Science.gov (United States)

    Guo, Kai; Yao, Jie; Yu, Qiang; Li, Zijian; Huang, Hu; Cheng, Jianguo; Wang, Zhigang; Zhu, Yunfeng

    2017-04-01

    The plasmacytoma variant translocation 1 gene (PVT1) is a large non-coding locus at adjacent of c-Myc, and long non-coding RNA PVT1 is now recognized as a cancerous gene co-amplified with c-Myc in various cancers. But the expression and functional role of PVT1 in colorectal cancer are still unelucidated. In addition, all the reported long non-coding RNAs so far are discovered in either cells or tissues, but no research about long non-coding RNAs detection in extracellular vesicles has been reported yet. In the present study, we firstly investigated the expression of PVT1 in colorectal cancer specimens and its correlation with the expression of c-Myc and other related genes by real-time polymerase chain reaction. Then, we isolated the extracellular vesicles from colorectal cancer cells culturing medium by differential centrifugation and detected the PVT1 expression in extracellular vesicles by using real-time polymerase chain reaction. The PVT1 targeting siRNA was transfected into SW480 and SW620 cells, and 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay and flow cytometry were used to evaluate the cell proliferation and apoptosis. The results showed that the PVT1 expression in tumor tissues was higher than that in normal tissues, which was significantly correlated with the expression of c-Myc and three c-Myc regulating genes FUBP1, EZH2, and NPM1 and also correlated with the expression of two other PVT1-associated transcript factors nuclear factor-κB and myocyte-specific enhancer factor 2A. Here, we reported for the first time that PVT1 as a long non-coding RNA was successfully detected in extracellular vesicles excluded from SW620 and SW480 cells, and the expression level of PVT1 was higher in extracellular vesicles from the more aggressive cell SW620 than from SW480. The results also showed that by down-regulating the PVT1 expression, the c-Myc expression was suppressed, the cell proliferation was inhibited, and

  18. [Aspirin and colorectal cancer].

    Science.gov (United States)

    Grancher, Adrien; Michel, Pierre; Di Fiore, Frédéric; Sefrioui, David

    2018-02-01

    Colorectal cancer is a worldwide public health problem. Aspirin has been identified as a protective factor against the apparition of colorectal cancer. There are several mechanisms about the actions by aspirin on colorectal tumorogenesis. These are not perfectly known nowadays. On one hand, there are direct mechanisms on colorectal mucosa, on the other hand there are indirect mechanisms through platelet functions. Aspirin also plays a role by its anti-inflammatory action and the stimulation of antitumor immunity. Several studies show that long-term treatment with low-doses of aspirin decreases the incidence of adenomas and colorectal cancers. In the United States, aspirin is currently recommended for primary prevention of the risk of colorectal cancer in all patients aged 50 to 59, with a 10-year risk of cardiovascular event greater than 10 %. However, primary prevention with aspirin should not be a substitute for screening in colorectal cancer. Furthermore, aspirin seems to be beneficial when used in post-diagnosis of colorectal cancer. It could actually decrease the risk of metastasis in case of a localized colorectal cancer, and increase the survival in particular, concerning PIK3CA mutated tumors. The association of aspirin with neoadjuvant treatment of colorectal cancer by radiochimiotherapy seems to have beneficial effects. French prospective randomized study is currently being conducted to investigate postoperative aspirin in colorectal cancers with a PIK3CA mutation. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  19. Epigenetics and Colorectal Cancer

    Science.gov (United States)

    Lao, Victoria Valinluck; Grady, William M.

    2012-01-01

    Colorectal cancer is a leading cause of cancer deaths in the world. It results from an accumulation of genetic and epigenetic changes in colon epithelial cells that transforms them into adenocarcinomas. There have been major advances in our understanding of cancer epigenetics over the last decade, particularly regarding aberrant DNA methylation. Assessment of the colon cancer epigenome has revealed that virtually all colorectal cancers have aberrantly methylated genes and the average colorectal cancer methylome has hundreds to thousands of abnormally methylated genes. As with gene mutations in the cancer genome, a subset of these methylated genes, called driver genes, is presumed to play a functional role in colorectal cancer. The assessment of methylated genes in colorectal cancers has also revealed a unique molecular subgroup of colorectal cancers called CpG Island Methylator Phenotype (CIMP) cancers; these tumors have a particularly high frequency of methylated genes. The advances in our understanding of aberrant methylation in colorectal cancer has led to epigenetic alterations being developed as clinical biomarkers for diagnostic, prognostic, and therapeutic applications. Progress in the assessment of epigenetic alterations in colorectal cancer and their clinical applications has shown that these alterations will be commonly used in the near future as molecular markers to direct the prevention and treatment of colorectal cancer. PMID:22009203

  20. Integrins are not essential for entry of coxsackievirus A9 into SW480 human colon adenocarcinoma cells.

    Science.gov (United States)

    Heikkilä, Outi; Merilahti, Pirjo; Hakanen, Marika; Karelehto, Eveliina; Alanko, Jonna; Sukki, Maria; Kiljunen, Saija; Susi, Petri

    2016-10-18

    Coxsackievirus A9 (CV-A9) is a pathogenic enterovirus type within the family Picornaviridae. CV-A9 infects A549 human epithelial lung carcinoma cells by attaching to the αVβ6 integrin receptor through a highly conserved Arg-Gly-Asp (RGD) motif, which is located at the exposed carboxy-terminus of the capsid protein VP1 detected in all studied clinical isolates. However, genetically-modified CV-A9 that lacks the RGD motif (CV-A9-RGDdel) has been shown to be infectious in some cell lines but not in A549, suggesting that RGD-mediated integrin binding is not always essential for efficient entry of CV-A9. Two cell lines, A549 and SW480, were used in the study. SW480 was the study object for the integrin-independent entry and A549 was used as the control for integrin-dependent entry. Receptor levels were quantitated by cell sorting and quantitative PCR. Antibody blocking assay and siRNA silencing of receptor-encoding genes were used to block virus infection. Peptide phage display library was used to identify peptide binders to CV-A9. Immunofluorescence and confocal microscopy were used to visualize the virus infection in the cells. We investigated the receptor use and early stages of CV-A9 internalization to SW480 human epithelial colon adenocarcinoma cells. Contrary to A549 infection, we showed that both CV-A9 and CV-A9-RGDdel internalized into SW480 cells and that function-blocking anti-αV integrin antibodies had no effect on the binding and entry of CV-A9. Whereas siRNA silencing of β6 integrin subunit had no influence on virus infection in SW480, silencing of β2-microglobulin (β2M) inhibited the virus infection in both cell lines. By using a peptide phage display screening, the virus-binding peptide identical to the N-terminal sequence of HSPA5 protein was identified and shown to block the virus infection in both A549 and SW480 cell lines. HSPA5 was also found to co-localize with CV-A9 at the SW480 cell periphery during the early stages of infection by confocal

  1. Protocatechualdehyde possesses anti-cancer activity through downregulating cyclin D1 and HDAC2 in human colorectal cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Jin Boo [Department of Nutrition and Food Science, University of Maryland, College Park, MD 20742 (United States); Lee, Seong-Ho, E-mail: slee2000@umd.edu [Department of Nutrition and Food Science, University of Maryland, College Park, MD 20742 (United States)

    2013-01-04

    Highlights: Black-Right-Pointing-Pointer Protocatechualdehyde (PCA) suppressed cell proliferation and induced apoptosis in human colorectal cancer cells. Black-Right-Pointing-Pointer PCA enhanced transcriptional downregulation of cyclin D1 gene. Black-Right-Pointing-Pointer PCA suppressed HDAC2 expression and activity. Black-Right-Pointing-Pointer These findings suggest that anti-cancer activity of PCA may be mediated by reducing HDAC2-derived cyclin D1 expression. -- Abstract: Protocatechualdehyde (PCA) is a naturally occurring polyphenol found in barley, green cavendish bananas, and grapevine leaves. Although a few studies reported growth-inhibitory activity of PCA in breast and leukemia cancer cells, the underlying mechanisms are still poorly understood. Thus, we performed in vitro study to investigate if treatment of PCA affects cell proliferation and apoptosis in human colorectal cancer cells and define potential mechanisms by which PCA mediates growth arrest and apoptosis of cancer cells. Exposure of PCA to human colorectal cancer cells (HCT116 and SW480 cells) suppressed cell growth and induced apoptosis in dose-dependent manner. PCA decreased cyclin D1 expression in protein and mRNA level and suppressed luciferase activity of cyclin D1 promoter, indicating transcriptional downregulation of cyclin D1 gene by PCA. We also observed that PCA treatment attenuated enzyme activity of histone deacetylase (HDAC) and reduced expression of HDAC2, but not HDAC1. These findings suggest that cell growth inhibition and apoptosis by PCA may be a result of HDAC2-mediated cyclin D1 suppression.

  2. Quantitative assessment of AKAP12 promoter methylation in colorectal cancer using methylation-sensitive high resolution melting: Correlation with Duke's stage.

    Science.gov (United States)

    Liu, Weiwei; Guan, Ming; Su, Bing; Ye, Chuanzhong; Li, Ji; Zhang, Xinju; Liu, Chunfang; Li, Min; Lin, Yong; Lu, Yuan

    2010-06-01

    The expression of AKAP12 (A Kinase anchoring protein 12) is markedly reduced in a variety of cancers. The purpose of this study was to establish a methylation-sensitive high resolution melting (MS-HRM) assay for the quantitative detection of AKAP12 promoter methylation and expression and the association with clinicopathological variables in human colorectal cancer. We also assessed the effect of AKAP12 re-expression on cell growth and colony formation. Downregulation or loss of AKAP12 mRNA expression was detected in 31 of 45 tissue samples (68.9%). No significant correlation was observed between the reduced expression levels and patient age, gender, Duke's stage or tumor differentiation. Methylation (>1%) of the AKAP12 promoter region was present in 35 of 45 (77.8%) carcinoma tissue samples and 6 of 45 (13.3%) adjacent tissue samples. AKAP12 methylation was significantly higher in the colorectal cancer tissues exhibiting advanced Duke's stages. Treatment of the three colorectal carcinoma cell lines (LoVo, COLO320 and SW480) with completely methylated AKAP12 with inhibitors of DNA methyltransferase (5-Aza-2'-deoxycytidine) markedly increased expression of AKAP12 and decreased methylation levels. Ectopic expression of AKAP12 in the LoVo cell line suppressed cell growth and inhibited colony formation. The AKAP12 gene was examined by quantitative RT-PCR, MS-HRM analysis and bisulfite sequencing in 45 paired tissue samples obtained from primary colorectal carcinomas and the corresponding adjacent tissues. In addition, five colorectal carcinoma cell lines (LoVo, COLO205, SW480, LS174T and COLO320) were investigated and western blot analysis was used to investigate changes in protein expression. A proliferation assay and soft agar assay were performed after overexpression of AKAP12. Our study demonstrated that MS-HRM is a robust, fast and sensitive method for AKAP12 methylation analysis. AKAP12 methylation represents a potential molecular biomarker for predicting the

  3. Human voltage-gated proton channel hv1: a new potential biomarker for diagnosis and prognosis of colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Yifan Wang

    Full Text Available Solid tumors exist in a hypoxic microenvironment, and possess high-glycolytic metabolites. To avoid the acidosis, tumor cells must exhibit a dynamic cytosolic pH regulation mechanism(s. The voltage-gated proton channel Hv1 mediates NADPH oxidase function by compensating cellular loss of electrons with protons. Here, we showed for the first time, that Hv1 expression is increased in colorectal tumor tissues and cell lines, associated with poor prognosis. Immunohistochemistry showed that Hv1 is strongly expressed in adenocarcinomas but not or lowly expressed in normal colorectal or hyperplastic polyps. Hv1 expression in colorectal cancer is significantly associated with the tumor size, tumor classification, lymph node status, clinical stage and p53 status. High Hv1 expression is associated significantly with shorter overall and recurrence-free survival. Furthermore, real-time RT-PCR and immunocytochemistry showed that Hv1 is highly expressed in colorectal cancer cell lines, SW620, HT29, LS174T and Colo205, but not in SW480. Inhibitions of Hv1 expression and activity in the highly metastatic SW620 cells by small interfering RNA (siRNA and Zn(2+ respectively, markedly decrease the cell invasion and migration, restraint proton extrusion and the intracellular pH recovery. Our results suggest that Hv1 may be used as a potential biomarker for diagnosis and prognosis of colorectal carcinoma, and a potential target for anticancer drugs in colorectal cancer therapy.

  4. Epigenetic-Mediated Downregulation of μ-Protocadherin in Colorectal Tumours

    Science.gov (United States)

    Mateusz, Bujko; Paulina, Kober; Małgorzata, Statkiewicz; Michal, Mikula; Marcin, Ligaj; Lech, Zwierzchowski; Jerzy, Ostrowski; Aleksander, Siedlecki Janusz

    2015-01-01

    Carcinogenesis involves altered cellular interaction and tissue morphology that partly arise from aberrant expression of cadherins. Mucin-like protocadherin is implicated in intercellular adhesion and its expression was found decreased in colorectal cancer (CRC). This study has compared MUPCDH (CDHR5) expression in three key types of colorectal tissue samples, for normal mucosa, adenoma, and carcinoma. A gradual decrease of mRNA levels and protein expression was observed in progressive stages of colorectal carcinogenesis which are consistent with reports of increasing MUPCDH 5′ promoter region DNA methylation. High MUPCDH methylation was also observed in HCT116 and SW480 CRC cell lines that revealed low gene expression levels compared to COLO205 and HT29 cell lines which lack DNA methylation at the MUPCDH locus. Furthermore, HCT116 and SW480 showed lower levels of RNA polymerase II and histone H3 lysine 4 trimethylation (H3K4me3) as well as higher levels of H3K27 trimethylation at the MUPCDH promoter. MUPCDH expression was however restored in HCT116 and SW480 cells in the presence of 5-Aza-2′-deoxycytidine (DNA methyltransferase inhibitor). Results indicate that μ-protocadherin downregulation occurs during early stages of tumourigenesis and progression into the adenoma-carcinoma sequence. Epigenetic mechanisms are involved in this silencing. PMID:25972897

  5. Interleukin-6 stimulates aerobic glycolysis by regulating PFKFB3 at early stage of colorectal cancer.

    Science.gov (United States)

    Han, Jun; Meng, Qingyang; Xi, Qiulei; Zhang, Yongxian; Zhuang, Qiulin; Han, Yusong; Jiang, Yi; Ding, Qiurong; Wu, Guohao

    2016-01-01

    Chronic inflammation is a well-known etiological factor for colorectal cancer (CRC) and cancer cells are known to preferentially metabolize glucose through aerobic glycolysis. However, the connection between chronic inflammation and aerobic glycolysis in the development of CRC is largely unexplored. The present study investigated whether interleukin-6 (IL-6), a pro-inflammatory cytokine, promotes the development of CRC by regulating the aerobic glycolysis and the underlying molecular mechanisms. In colitis-associated CRC mouse, anti-IL-6 receptor antibody treatment reduced the incidence of CRC and decreased the expression of key genes in aerobic glycolysis, whereas the plasma concentrations of glucose and lactate were not affected. Consistently, IL-6 treatment stimulated aerobic glycolysis, upregulated key genes in aerobic glycolysis and promoted cell proliferation and migration in SW480 and SW1116 CRC cells. 6-phoshofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3) was the most downregulated gene by anti-IL-6 receptor antibody in colorectal adenoma tissues. Further analysis in human samples revealed overexpression of PFKFB3 in colorectal adenoma and adenocarcinoma tissues, which was also associated with lymph node metastasis, intravascular cancer embolus and TNM stage. In addition, the effect of IL-6 on CRC cells can be abolished by knocking down PRKFB3 through siRNA transfection. Our data suggest that chronic inflammation promotes the development of CRC by stimulating aerobic glycolysis and IL-6 is functioning, at least partly, through regulating PFKFB3 at early stage of CRC.

  6. Gallstones and colorectal cancer

    DEFF Research Database (Denmark)

    Jørgensen, Torben; Rafaelsen, Søren Rafael

    1992-01-01

    The prevalence of gallstone disease in 145 consecutive patients with colorectal cancer was compared with gallstone prevalence in 4,159 subjects randomly selected from a population. The group of patients had a significantly higher prevalence of gallstone disease than the population (odds ratio = 1.......59; 95 percent confidence limits 1.04-2.45), whereas cholecystectomies occurred with equal frequency in the two groups. There was a nonsignificant trend toward more right-sided cancers in patients with gallstones than in patients without. These results, together with available literature, give...... substantial evidence for an association between gallstones and colorectal cancer, an association which is not due to cholecystectomy being a predisposing factor to colorectal cancer. Sporadic findings of an association between cholecystectomy and colorectal cancer can be explained by the above relationship....

  7. Prophylaxis against colorectal cancer

    DEFF Research Database (Denmark)

    Bülow, Steffen; Kronborg, O

    1996-01-01

    Colorectal cancer is diagnosed in more than 3000 people every year in Denmark, with a population of 5 million, and 2000 die from this disease every year. The aetiology of the disease is complex, but an increasing number of cancers have been related to genetics and Denmark is contributing...... with a well-established register of familial adenomatous polyposis and a recently founded register for hereditary nonpolyposis colorectal cancer, both with major international relationships. The Danish tradition of epidemiology and clinical trials has also been demonstrated in population screening trials...... for colorectal cancer in average-risk persons as well as high-risk groups with precursors of the disease. The present review places Danish contributions within the prophylaxis of colorectal cancer during the last decade in an international context....

  8. Anticancer effects of sweet potato protein on human colorectal cancer cells.

    Science.gov (United States)

    Li, Peng-Gao; Mu, Tai-Hua; Deng, Le

    2013-06-07

    To investigate the effects of proteins purified from sweet potato storage roots on human colorectal cancer cell lines. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Hoechst 33258 nuclear staining and Boyden transwell chamber methods were used to determine whether purified sweet potato protein (SPP) from fresh sweet potato roots affected proliferation, migration and invasion, respectively, of human colorectal cancer SW480 cells in vitro. The inhibitory effects of SPP on growth of human colorectal cancer HCT-8 cells intraperitoneally xenografted in nude mice and spontaneous lung metastasis of murine Lewis lung carcinoma 3LL cells subcutaneously transplanted in C57 BL/6 mice were also investigated in vivo. SPP inhibited the proliferation of SW480 cells in a dose-dependent manner, with an IC50 value of 38.732 μmol/L (r (2) = 0.980, P = 0.003) in the MTT assay. Hoechst 33258 nuclear staining further revealed inhibition of cell viability and induction of apoptosis by SPP. The transwell assay disclosed significant reduction in migrated cells/field by 8 μmol/L SPP (8.4 ± 2.6 vs 23.3 ± 5.4, P = 0.031) and invaded cells/field through the ECMatrix by 0.8 μmol/L SPP, compared with the control (25.2 ± 5.2 vs 34.8 ± 6.1, P = 0.038). Both intraperitoneal (ip) and intragastric (ig) administration of SPP led to significant suppression of growth of intraperitoneally inoculated HCT-8 cells in nude mice to 58.0% ± 5.9% (P = 0.037) and 43.5% ± 7.1% (P = 0.004) of the controls, respectively, after 9 d treatment. Bloody ascites additionally disappeared after ip injection of trypsin inhibitor. Notably, ig and ip administration of SPP induced a significant decrease in spontaneous pulmonary metastatic nodule formation in C57 BL/6 mice (21.0 ± 12.3 and 27.3 ± 12.7 nodules/lung vs 42.5 ± 4.5 nodules/lung in controls, respectively, P < 0.05) after 25 d treatment. Moreover, the average weight of primary tumor nodules in the hind leg of mice decreased from

  9. Developments in Colorectal Cancer Screening

    Science.gov (United States)

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

  10. Hereditary colorectal cancer diagnostics

    DEFF Research Database (Denmark)

    Klarskov, Louise; Holck, Susanne; Bernstein, Inge

    2012-01-01

    BackgroundThe hereditary non-polyposis colorectal cancer (HNPCC) subset of tumours can broadly be divided into tumours caused by an underlying mismatch-repair gene mutation, referred to as Lynch syndrome, and those that develop in families with similar patterns of heredity but without disease......-predisposing germline mismatch repair mutations, referred to as familial colorectal cancer type X (FCCTX). Recognition of HNPCC-associated colorectal cancers is central since surveillance programmes effectively reduce morbidity and mortality. The characteristic morphological features linked to Lynch syndrome can aid...... in the identification of this subset, whereas the possibility to use morphological features as an indicator of FCCTX is uncertain.Objective and methodsTo perform a detailed morphological evaluation of HNPCC-associated colorectal cancers and demonstrate significant differences between tumours associated with FCCTX...

  11. MicroRNA-375 inhibits colorectal cancer growth by targeting PIK3CA

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yihui [Department of Colorectal Surgery, The Third Affiliated Hospital of Harbin Medical University, 150 Haping Road, 150081 Harbin (China); Tang, Qingchao [Cancer Center, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, 150086 Harbin (China); Li, Mingqi; Jiang, Shixiong [Department of Colorectal Surgery, The Third Affiliated Hospital of Harbin Medical University, 150 Haping Road, 150081 Harbin (China); Wang, Xishan, E-mail: wxshan12081@163.com [Cancer Center, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, 150086 Harbin (China)

    2014-02-07

    Highlights: • miR-375 is downregulated in colorectal cancer cell lines and tissues. • miR-375 inhibits colorectal cancer cell growth by targeting PIK3CA. • miR-375 inhibits colorectal cancer cell growth in xenograft nude mice model. - Abstract: Colorectal cancer (CRC) is the second most common cause of death from cancer. MicroRNAs (miRNAs) represent a class of small non-coding RNAs that control gene expression by triggering RNA degradation or interfering with translation. Aberrant miRNA expression is involved in human disease including cancer. Herein, we showed that miR-375 was frequently down-regulated in human colorectal cancer cell lines and tissues when compared to normal human colon tissues. PIK3CA was identified as a potential miR-375 target by bioinformatics. Overexpression of miR-375 in SW480 and HCT15 cells reduced PIK3CA protein expression. Subsequently, using reporter constructs, we showed that the PIK3CA untranslated region (3′-UTR) carries the directly binding site of miR-375. Additionally, miR-375 suppressed CRC cell proliferation and colony formation and led to cell cycle arrest. Furthermore, miR-375 overexpression resulted in inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. SiRNA-mediated silencing of PIK3CA blocked the inhibitory effect of miR-375 on CRC cell growth. Lastly, we found overexpressed miR-375 effectively repressed tumor growth in xenograft animal experiments. Taken together, we propose that overexpression of miR-375 may provide a selective growth inhibition for CRC cells by targeting PI3K/Akt signaling pathway.

  12. Cytotoxic and Apoptotic Activities of Prunus spinosa Trigno Ecotype Extract on Human Cancer Cells

    Directory of Open Access Journals (Sweden)

    Stefania Meschini

    2017-09-01

    Full Text Available The aim of this work was to demonstrate that a natural compound, not-toxic to normal cells, has cytotoxic and sensitizing effects on carcinoma cells, with the final goal of combining it with chemotherapeutic drugs to reduce the overall dose. Prunus spinosa Trigno ecotype (PsT drupe extract with a nutraceutical activator complex (NAC made of amino acids, vitamins and mineral salt blends, has shown in vitro anticancer activity. The cytotoxic effect of (PsT + NAC® has been evaluated on human cancer cells, with an initial screening with colorectal, uterine cervical, and bronchoalveolar cells, and a subsequent focus on colon carcinoma cells HCT116 and SW480. The viability reduction of HCT116 and SW480 after treatment with (PsT 10 mg/mL + NAC® was about 40% (p < 0.05, compared to control cells. The cell’s survival reduction was ineffective when the drug vehicle (NAC was replaced with a phosphate buffer saline (PBS or physiological solution (PS. The flow cytometry evaluation of cancer cells’ mitochondrial membrane potential showed an increase of 20% depolarized mitochondria. Cell cycle analysis showed a sub G1 (Gap 1 phase peak appearance (HCT116: 35.1%; SW480: 11.6%, indicating apoptotic cell death induction that was confirmed by Annexin V assay (HCT116: 86%; SW480: 96%. Normal cells were not altered by (PsT + NAC® treatments.

  13. Induction of ROS Overload by Alantolactone Prompts Oxidative DNA Damage and Apoptosis in Colorectal Cancer Cells

    Directory of Open Access Journals (Sweden)

    Yushuang Ding

    2016-04-01

    Full Text Available Cancer cells typically display higher than normal levels of reactive oxygen species (ROS, which may promote cancer development and progression but may also render the cancer cells more vulnerable to further ROS insult. Indeed, many of the current anticancer therapeutics kill cancer cells via induction of oxidative stress, though they target both cancer and normal cells. Recently, alantolactone (ATL, a natural sesquiterpene lactone, has been shown to induce apoptosis by increasing ROS levels specifically in cancer cells; however, the molecular mechanisms linking ROS overproduction to apoptosis remain unclear. Here we show that the ATL-induced ROS overload in human SW480 and SW1116 colorectal cancer cells was followed by a prominent accumulation of cellular oxidized guanine (8-oxoG and immediate increase in the number of DNA strand breaks, indicating that increased ROS resulted in extensive oxidative DNA damage. Consequently, the G1/S-CDK suppresser CDKN1B (p21 and pro-apoptotic proteins Bax and activated caspase-3 were upregulated, while anti-apoptotic Bcl-2 was downregulated, which were followed by cell cycle arrest at G1 and marked apoptosis in ATL-treated cancer but not non-cancer cells. These results suggest that the ATL-induced ROS overload triggers cell death through induction of massive oxidative DNA damage and subsequent activation of the intrinsic apoptosis pathway.

  14. A novel cell type-specific role of p38alpha in the control of autophagy and cell death in colorectal cancer cells.

    Science.gov (United States)

    Comes, F; Matrone, A; Lastella, P; Nico, B; Susca, F C; Bagnulo, R; Ingravallo, G; Modica, S; Lo Sasso, G; Moschetta, A; Guanti, G; Simone, C

    2007-04-01

    Cancer develops when molecular pathways that control the fine balance between proliferation, differentiation, autophagy and cell death undergo genetic deregulation. The prospects for further substantial advances in the management of colorectal cancer reside in a systematic genetic and functional dissection of these pathways in tumor cells. In an effort to evaluate the impact of p38 signaling on colorectal cancer cell fate, we treated HT29, Caco2, Hct116, LS174T and SW480 cell lines with the inhibitor SB202190 specific for p38alpha/beta kinases. We report that p38alpha is required for colorectal cancer cell homeostasis as the inhibition of its kinase function by pharmacological blockade or genetic inactivation causes cell cycle arrest, autophagy and cell death in a cell type-specific manner. Deficiency of p38alpha activity induces a tissue-restricted upregulation of the GABARAP gene, an essential component of autophagic vacuoles and autophagosomes, whereas simultaneous inhibition of autophagy significantly increases cell death by triggering apoptosis. These data identify p38alpha as a central mediator of colorectal cancer cell homeostasis and establish a rationale for the evaluation of the pharmacological manipulation of the p38alpha pathway in the treatment of colorectal cancer.

  15. Colorectal Cancer Risk Assessment Tool

    Science.gov (United States)

    ... know before using this tool: The Colorectal Cancer Risk Assessment Tool was designed for use by doctors and other health providers with their patients. If you are not a health ... your personal risk of colorectal cancer. (Colorectal cancer is another way ...

  16. Osteopontin-enhanced hepatic metastasis of colorectal cancer cells.

    Directory of Open Access Journals (Sweden)

    Jianjin Huang

    Full Text Available Liver metastasis is a major cause of mortality from colorectal cancer (CRC. However, mechanisms underlying this process are largely unknown. Osteopontin (OPN is a secreted phosphorylated glycoprotein that is involved in tumor migration and metastasis. The role of OPN in cancer is currently unclear. In this study, OPN mRNA was examined in tissues from CRC, adjacent normal mucosa, and liver metastatic lesions using quantitative real-time PCR analysis. The protein expression of OPN and its receptors (integrin αv and CD44 v6 was detected by using an immunohistochemical (IHC method. The role of OPN in liver metastasis was studied in established colon cancer Colo-205 and SW-480 cell lines transfected with sense- or antisense-OPN eukaryotic expression plasmids by flow cytometry and cell adhesion assay. Fluorescence redistribution after photobleaching (FRAP was used to study gap functional intercellular communication (GJIC among OPN-transfected cells. It was found that OPN was highly expressed in metastatic hepatic lesions from CRC compared to primary CRC tissue and adjacent normal mucosa. The expression of OPN mRNA in tumor tissues was significantly related with the CRC stages. OPN expression was also detected in normal hepatocytes surrounding CRC metastatic lesions. Two known receptors of OPN, integrin αv and CD44v6 proteins, were strongly expressed in hepatocytes from normal liver. CRC cells with forced OPN expression exhibited increased heterotypic adhesion with endothelial cells and weakened intercellular communication. OPN plays a significant role in CRC metastasis to liver through interaction with its receptors in hepatocytes, decreased homotypic adhesion, and enhanced heterotypic adhesion.

  17. Snail and serpinA1 promote tumor progression and predict prognosis in colorectal cancer.

    Science.gov (United States)

    Kwon, Chae Hwa; Park, Hye Ji; Choi, Jin Hwa; Lee, Ja Rang; Kim, Hye Kyung; Jo, Hong-Jae; Kim, Hyun Sung; Oh, Nahmgun; Song, Geun Am; Park, Do Youn

    2015-08-21

    The role of Snail and serpin peptidase inhibitor clade A member 1 (serpinA1) in tumorigenesis has been previously identified. However, the exact role and mechanism of these proteins in progression of colorectal cancer (CRC) are controversial. In this study, we investigated the role of Snail and serpinA1 in colorectal cancer (CRC) and examined the mechanisms through which these proteins mediate CRC progression. Immunohistochemical analysis of 528 samples from patients with CRC showed that elevated expression of Snail or serpinA1 was correlated with advanced stage, lymph node metastasis, and poor prognosis. Moreover, we detected a correlation between Snail and serpinA1 expression. Functional studies performed using the CRC cell lines DLD-1 and SW-480 showed that overexpression of Snail or serpinA1 significantly increased CRC cell invasion and migration. Conversely, knockdown of Snail or serpinA1 expression suppressed CRC cell invasion and migration. ChIP analysis revealed that Snail regulated serpinA1 by binding to its promoter. In addition, fibronectin mediated Snail and serpinA1 signaling was involved in CRC cell invasion and migration. Taken together, our data showed that Snail and serpinA1 promoted CRC progression through fibronectin. These findings suggested that Snail and serpinA1 were novel prognostic biomarkers and candidate therapeutic targets in CRC.

  18. Survivin-miRNA-loaded nanoparticles as auxiliary tools for radiation therapy: preparation, characterisation, drug release, cytotoxicity and therapeutic effect on colorectal cancer cells.

    Science.gov (United States)

    Gaca, Sebastian; Reichert, Sebastian; Rödel, Claus; Rödel, Franz; Kreuter, Jörg

    2012-01-01

    One of the main challenges in radiation oncology is to overcome the resistance of cancer cells against treatment by molecular targeted approaches. Among the most promising targets is the inhibitor of apoptosis protein survivin, known to be associated with increased tumour aggressiveness and therapy resistance. The objective of this study was the development of a human serum albumin-based nanoparticulate carrier system for plasmid-mediated RNA interference (miRNA) and the investigation of its in vitro efficacy on survivin knockdown and cellular toxicity in SW480 colorectal cancer cells. The results demonstrate a robust nanoparticulate system of a size around 220 nm with a plasmid incorporation efficacy of about 90%. Moreover, treatment of carcinoma cells with survivin-miRNA nanoparticles resulted in reduction of survivin expression by 50% and increased cytotoxicity if combined with ionising irradiation. These nanoparticles comprise a promising option to enhance the response of carcinoma cells to therapy with ionising irradiation.

  19. Colorectal Cancer: A Personal Journey

    Science.gov (United States)

    ... be as fortunate as we are.” Reflecting what research has proven, Valvo’s message is clear. “Screening is so important! Early detection is early cure!” Read More "Colorectal Cancer" Articles Colorectal Cancer: A Personal Journey / The Importance of Early Detection / Developments in Colorectal ...

  20. [Nutrition and colorectal cancer].

    Science.gov (United States)

    Ströhle, Alexander; Maike, Wolters; Hahn, Andreas

    2007-01-01

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

  1. [Nationwide colorectal cancer screening].

    NARCIS (Netherlands)

    Rossum, L.G.M. van; Laheij, R.J.F.; Jansen, J.B.M.J.

    2010-01-01

    Usually, colorectal cancer presents with complaints in a late stage, but can be detected in an earlier stage, with better prognosis, by colonoscopy. Using colonoscopy, also precancerous tumours, adenomas, can be detected and excised, but only in a national screening programme. However primary

  2. [Colorectal cancer screening].

    Science.gov (United States)

    Castells, Antoni

    2015-09-01

    Colorectal cancer is one of malignancies showing the greatest benefit from preventive measures, especially screening or secondary prevention. Several screening strategies are available with demonstrated efficacy and efficiency. The most widely used are the faecal occult blood test in countries with population-based screening programmes, and colonoscopy in those conducting opportunistic screening. The present article reviews the most important presentations on colorectal cancer screening at the annual congress of the American Gastroenterological Association held in Washington in 2015, with special emphasis on the medium-term results of faecal occult blood testing strategies and determining factors and on strategies to reduce the development of interval cancer after colonoscopy. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  3. Microbiota, Inflammation and Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Cécily Lucas

    2017-06-01

    Full Text Available Colorectal cancer, the fourth leading cause of cancer-related death worldwide, is a multifactorial disease involving genetic, environmental and lifestyle risk factors. In addition, increased evidence has established a role for the intestinal microbiota in the development of colorectal cancer. Indeed, changes in the intestinal microbiota composition in colorectal cancer patients compared to control subjects have been reported. Several bacterial species have been shown to exhibit the pro-inflammatory and pro-carcinogenic properties, which could consequently have an impact on colorectal carcinogenesis. This review will summarize the current knowledge about the potential links between the intestinal microbiota and colorectal cancer, with a focus on the pro-carcinogenic properties of bacterial microbiota such as induction of inflammation, the biosynthesis of genotoxins that interfere with cell cycle regulation and the production of toxic metabolites. Finally, we will describe the potential therapeutic strategies based on intestinal microbiota manipulation for colorectal cancer treatment.

  4. Colorectal cancer screening.

    Science.gov (United States)

    Bessa Caserras, Xavier

    2016-09-01

    In the latest meeting of the American Gastroenterological Association, several clinical studies were presented that aimed to evaluate the various colorectal cancer screening strategies, although most assessed the various aspects of faecal immunochemical testing (FIT) and colonoscopy. Data were presented from consecutive FIT-based screening rounds, confirming the importance of adherence to consecutive screening rounds, achieving a similar or superior diagnostic yield to endoscopic studies. There was confirmation of the importance of not delaying endoscopic study after a positive result. Participants with a negative FIT (score of 0) had a low risk for colorectal cancer. Several studies seemed to confirm the importance of high-quality colonoscopy in colorectal cancer screening programmes. The implementation of high-quality colonoscopies has reduced mortality from proximal lesions and reduced interval cancers in various studies. Finally, participants with a normal colonoscopy result or with a small adenoma are at low risk for developing advanced neoplasms during follow-up. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  5. Screening for colorectal cancer

    DEFF Research Database (Denmark)

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

    2011-01-01

    Emerging results indicate that screening improves survival of patients with colorectal cancer. Therefore, screening programs are already implemented or are being considered for implementation in Asia, Europe and North America. At present, a great variety of screening methods are available including...... colono- and sigmoidoscopy, CT- and MR-colonography, capsule endoscopy, DNA and occult blood in feces, and so on. The pros and cons of the various tests, including economic issues, are debated. Although a plethora of evaluated and validated tests even with high specificities and reasonable sensitivities...... into improvements of screening for colorectal cancer includes blood-based biological markers, such as proteins, DNA and RNA in combination with various demographically and clinically parameters into a "risk assessment evaluation" (RAE) test. It is assumed that such a test may lead to higher acceptance among...

  6. Improving colorectal cancer referrals

    OpenAIRE

    Gregory, Claire

    2018-01-01

    The colorectal services at The Royal Bournemouth Hospital needed to adapt to meet the extra demand on fast-track patient referrals to the outpatient department, as a consequence of the changes in the National Institute for Health and Care Excellence (NICE) guidance on cancer referrals in June 2015. Learning from other units, a telephone assessment clinic (TAC) triaging patients straight to colonoscopy was trialled. A Plan–Do–Study–Act (PDSA) methodology was used. A baseline study showed that ...

  7. Effect of [10]-Gingerol on [Ca2+]i and Cell Death in Human Colorectal Cancer Cells

    Directory of Open Access Journals (Sweden)

    Chung-Yi Chen

    2009-03-01

    Full Text Available The effect of [10]-gingerol on cytosol free Ca2+ concentration ([Ca2+]i and viability is large unknown. This study examines the early signaling effects of [10]-gingerol on human colorectal cancer cells. It was found that this compound caused a slow and sustained rise of [Ca2+]i in a concentration-dependent manner. [10]-Gingerol also induced a [Ca2+]i rise when extracellular Ca2+ was removed, but the magnitude was reduced by 38%. In a Ca2+-free medium, the [10]-gingerol-induced [Ca2+]i rise was partially abolished by depleting stored Ca2+ with thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor. The elevation of [10]-gingerol-caused [Ca2+]i in a Ca2+-containing medium was not affected by modulation of protein kinase C activity. The [10]-gingerol-induced Ca2+ influx was insensitive to L-type Ca2+ channel blockers. At concentrations of 10-100 mM, [10]-gingerol killed cells in a concentration-dependent manner. These findings suggest that [10]-gingerol induces [Ca2+]i rise by causing Ca2+ release from the endoplasmic reticulum and Ca2+ influx from non-L-type Ca2+ channels in SW480 cancer cells.

  8. [Colorectal cancer screening].

    Science.gov (United States)

    Castells, Antoni

    2013-10-01

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

  9. Krill oil extract suppresses cell growth and induces apoptosis of human colorectal cancer cells.

    Science.gov (United States)

    Jayathilake, Abilasha Gayani; Senior, Paul Vincent; Su, Xiao Qun

    2016-08-30

    Colorectal cancer (CRC) is the third most common cancer in the world. The current available treatments for CRC include surgery, chemotherapy and radiotherapy. However, surgery is only useful when the disease is diagnosed at the earlier stage. Chemotherapy and radiotherapy are associated with numerous side effects that decrease the patients' quality of life. Safer, effective alternatives, such as natural compounds, to chemotherapy are desirable. This study assessed the efficacy of free fatty acid (FFA) extract of krill oil on three human CRC cells lines. HCT-15, SW-480 and Caco-2 cells were treated with the FFA extracts of krill oil and fish oil for 48 h while treatments with the bioactive omega-3 polyunsaturated fatty acids (LC n-3 PUFA) of these marine oils, eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid (DHA, C22:6n-3) in comparison with a n-6 PUFA, arachnoid acid (AA, C20:4n-6) were up to 72 h at the concentrations of 50, 100, 150 and 200 μM. Effects of all the treatments on cell proliferation were assessed using a water-soluble tetrazolium-1 (WST-1) assay kit at 24, 48 and 72 h. Effects of FFA extract of krill oil and EPA on apoptosis and mitochondrial membrane potential were determined using commercial kits after 48 h of treatment. Krill oil extract inhibited cell proliferation of all three cell lines in the similar manner as fish oil extract. A significant cell apoptosis and increase in mitochondrial membrane potential were observed after the treatment with krill oil extract. EPA at the concentration of 200 μM reduced significantly the proliferation of HCT-15 and SW-480 at 24, 48 and 72 h. In addition, EPA treatment (100 and 200 μM) resulted in significant cell apoptosis in all three cell lines. No significant changes were observed after treatment with DHA and AA. Our results indicate that the FFA extract of krill oil maybe an effective chemotherapeutic agent to suppress proliferation and induce apoptosis in CRC cells through its

  10. miR-300 promotes proliferation and EMT-mediated colorectal cancer migration and invasion by targeting p53.

    Science.gov (United States)

    Wang, Lin; Yu, Peiwu

    2016-12-01

    p53 mutations in tumors can induce the loss of wild-type tumor-suppressing p53 function, which results in the increase in proliferation, migration and invasion ability in cancer cells. Studies have shown that the expression of p53 is regulated by several microRNAs (miRNAs). In the present study, we found that miR-300 and p53 were significantly increased in colorectal cancer (CRC) tissues when compared with levels noted in adjacent colorectal tissues. Both miR-300 and p53 were significantly correlated with lymphatic metastasis and TNM stage. Both miR-300 and p53 promoted CRC cell (SW480 and HT29) proliferation, migration, and invasion, respectively, in vitro. In addition, we found that miR-300 is a direct positive regulator of p53 through binding to the binding site in the 3'UTR of the p53 gene in human CRC cells. Moreover, both miR-300 and p53 induced CRC cell epithelial‑mesenchymal transition (EMT) respectively. Taken together, we demonstrated that miR-300 promoted proliferation and EMT-mediated CRC migration and invasion by targeting p53. These findings provide a new theoretical basis and potential therapeutic targets, and thus lays the foundation for exploring the pathogenesis of CRC.

  11. HIV Nef-M1 Effects on Colorectal Cancer Growth in Tumor-induced Spleens and Hepatic Metastasis.

    Science.gov (United States)

    Harrington, Willie; Bond, Vincent; Huang, Ming Bo; Powell, Michael; Lillard, James; Manne, Upender; Bumpers, Harvey

    2009-08-05

    CXCR4 receptors have been implicated in tumorigenesis and proliferation, making it a potential target for colorectal cancer therapy. Expression of this chemokine receptor on cellular surfaces appears to promote metastasis by directly stimulating tumor cell migration and invasion. The receptor/ligand, CXCR4/SDF-1alpha, pair are critically important to angiogenesis and vascular remodeling which supports cancer proliferation. Our work has shown that a novel apoptotic peptide of HIV-1, Nef-M1, can act as a CXCR4 antagonist, inducing apoptosis in CXCR4 containing cells. Four colorectal tumor cell lines (HT-29, LS174t, SW480, WiDr), were evaluated for their response to Nef-M1 peptide via in vivo and in vitro. The presence of CXCR4 receptors on tumor cells was determined using immunohistochemical and RT-PCR analyses. Solid xenografts derived from tumor cell lines grown in SCID mice, were evaluated for the persistence of the receptor. Xenografts propagated in SCID mice from each of the four cell lines demonstrated high levels of receptor expression as well. The effects of Nef-M1 in vivo via splenic injected mice and subsequent hepatic metastasis also demonstrated dramatic reduction of primary tumor growth in the spleen and secondary invasion of the liver. We concluded that Nef-M1 peptide, through physical interaction(s) with CXCR4, drives apoptotic reduction in in vivo primary tumor growth and metastasis.

  12. Involvement of the Integrin α1β1 in the Progression of Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Salah Boudjadi

    2017-07-01

    Full Text Available Integrins are a family of heterodimeric glycoproteins involved in bidirectional cell signaling that participate in the regulation of cell shape, adhesion, migration, survival and proliferation. The integrin α1β1 is known to be involved in RAS/ERK proliferative pathway activation and plays an important role in fibroblast proliferation. In the small intestine, the integrin α1 subunit is present in the crypt proliferative compartment and absent in the villus. We have recently shown that the integrin α1 protein and transcript (ITGA1 are present in a large proportion of colorectal cancers (CRC and that their expression is controlled by the MYC oncogenic factor. Considering that α1 subunit/ITGA1 expression is correlated with MYC in more than 70% of colon adenocarcinomas, we postulated that the integrin α1β1 has a pro-tumoral contribution to CRC. In HT29, T84 and SW480 CRC cells, α1 subunit/ITGA1 knockdown resulted in a reduction of cell proliferation associated with an impaired resistance to anoikis and an altered cell migration in HT29 and T84 cells. Moreover, tumor development in xenografts was reduced in HT29 and T84 sh-ITGA1 cells, associated with extensive necrosis, a low mitotic index and a reduced number of blood vessels. Our results show that α1β1 is involved in tumor cell proliferation, survival and migration. This finding suggests that α1β1 contributes to CRC progression.

  13. Epigenetics of colorectal cancer.

    Science.gov (United States)

    Goel, Ajay; Boland, C Richard

    2012-12-01

    In the early years of the molecular biology revolution, cancer research was mainly focused on genetic changes (ie, those that altered DNA sequences). Although this has been extremely useful as our understanding of the pathogenesis and biology of cancer has grown and matured, there is another realm in tumor development that does not involve changing the sequence of cellular DNA. This field is called "epigenetics" and broadly encompasses changes in the methylation of cytosines in DNA, changes in histone and chromatin structure, and alterations in the expression of microRNAs, which control the stability of many messenger RNAs and serve as "master regulators" of gene expression. This review focuses on the epigenetics of colorectal cancer and illustrates the impact epigenetics has had on this field. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

  14. Lysyl oxidase in colorectal cancer.

    Science.gov (United States)

    Cox, Thomas R; Erler, Janine T

    2013-11-15

    Colorectal cancer is the third most prevalent form of cancer worldwide and fourth-leading cause of cancer-related mortality, leading to ~600,000 deaths annually, predominantly affecting the developed world. Lysyl oxidase is a secreted, extracellular matrix-modifying enzyme previously suggested to act as a tumor suppressor in colorectal cancer. However, emerging evidence has rapidly implicated lysyl oxidase in promoting metastasis of solid tumors and in particular colorectal cancer at multiple stages, affecting tumor cell proliferation, invasion, and angiogenesis. This emerging research has stimulated significant interest in lysyl oxidase as a strong candidate for developing and deploying inhibitors as functional efficacious cancer therapeutics. In this review, we discuss the rapidly expanding body of knowledge concerning lysyl oxidase in solid tumor progression, highlighting recent advancements in the field of colorectal cancer.

  15. [Genetics of colorectal cancer].

    Science.gov (United States)

    Balaguer, Francesc

    2013-10-01

    Up to 5% of all cases of colorectal cancer (CRC) are due to a known hereditary syndrome. These hereditary forms often require a high degree of suspicion for their diagnosis and specific and specialized management. Moreover, a diagnosis of hereditary CRC has important consequences, not only for patients-for whom highly effective preventive measures are available-, but also for their relatives, who may be carriers of the same condition. The most significant advances in the field of hereditary CRC have been produced in the diagnosis and characterization of these syndromes and in the discovery of new causative genes. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  16. [Epigenetics and colorectal cancer].

    Science.gov (United States)

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

    2012-05-01

    The epigenetic and physiological mechanisms that alter the structure of chromatin include the methylation of DNA, changes in the histones, and changes in RNA. A literature review has been carried out using PubMed on the evidence published on the association between epigenetics and colorectal cancer. The scientific literature shows that epigenetic changes, such as genetic modifications may be very significant in the origin of neoplastic disease, contributing both to the development and progression of the disease. Copyright © 2011 AEC. Published by Elsevier Espana. All rights reserved.

  17. Induction of Apoptosis and Cell Cycle Arrest in Human Colorectal Carcinoma by Litchi Seed Extract

    Directory of Open Access Journals (Sweden)

    Chih-Ping Hsu

    2012-01-01

    Full Text Available The Litchi (Litchi chinensis fruit products possess rich amounts of flavanoids and proanthocyanidins. Its pericarp has been shown to inhibit breast and liver cancer cell growth. However, the anticolorectal cancer effect of Litchi seed extract has not yet been reported. In this study, the effects of polyphenol-rich Litchi seed ethanol extract (LCSP on the proliferation, cell cycle, and apoptosis of two colorectal cancer cell lines Colo320DM and SW480 were examined. The results demonstrated that LCSP significantly induced apoptotic cell death in a dose-dependent manner and arrested cell cycle in G2/M in colorectal carcinoma cells. LCSP also suppressed cyclins and elevated the Bax : Bcl-2 ratio and caspase 3 activity. This study provides in vitro evidence that LCSP serves as a potential chemopreventive agent for colorectal cancer.

  18. Epifluorescent imaging study of the effect of anti-diabetic drug metformin on colorectal cancer cell lines in vitro

    Directory of Open Access Journals (Sweden)

    Venkatasubramani P

    2017-12-01

    Full Text Available Metformin, a widely used anti-diabetic drug, has recently been associated with inhibition of cell proliferation in multiple cancers. However, it is not clear if the reduction in proliferation on treatment with metformin is a result of cell death or slowdown in the rate of growth of cancer cells, because cell viability assays measure only the number of cells at the beginning and end of the experiment. The aim of this study is to utilize a fluorescent imaging technique to directly follow cell death overtime in order to investigate the effect of metformin on colorectal cancer cells HCT116 and SW480. Epifluorescent imaging analysis carried out using ImageXpress Micro XLS High-Content Imaging System show that there is no significant change in cell death observed in the cancer cell lines, as compared to the control, over multiple closely spaced time points, suggesting that metformin in pharmacological doses may not be an effective inducer of cell death in these colon cancer cell lines.

  19. Primary Prevention of Colorectal Cancer

    Science.gov (United States)

    Chan, Andrew T.; Giovannucci, Edward L.

    2010-01-01

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

  20. The cardiac glycoside oleandrin induces apoptosis in human colon cancer cells via the mitochondrial pathway.

    Science.gov (United States)

    Pan, Li; Zhang, Yuming; Zhao, Wanlu; Zhou, Xia; Wang, Chunxia; Deng, Fan

    2017-07-01

    Evidence indicates that the cardiac glycoside oleandrin exhibits cytotoxic activity against several different types of cancer. However, the specific mechanisms underlying oleandrin-induced anti-tumor effects remain largely unknown. The present study examined the anti-cancer effect and underlying mechanism of oleandrin on human colon cancer cells. The cytotoxicity and IC50 of five small molecule compounds (oleandrin, neriifolin, strophanthidin, gitoxigenin, and convallatoxin) in human colon cancer cell line SW480 cells and normal human colon cell line NCM460 cells were determined by cell counting and MTT assays, respectively. Apoptosis was determined by staining cells with annexin V-FITC and propidium iodide, followed by flow cytometry. Intracellular Ca2+ was determined using Fluo-3 AM,glutathione (GSH) levels were measured using a GSH detection kit,and the activity of caspase-3, -9 was measured using a peptide substrate. BAX, pro-caspase-3, -9, cytochrome C and BCL-2 expression were determined by Western blotting. Oleandrin significantly decreased cell viabilities in SW480, HCT116 and RKO cells. The IC50 for SW480 cells was 0.02 µM, whereas for NCM460 cells 0.56 µM. More interestingly, the results of flow cytometry showed that oleandrin potently induced apoptosis in SW480 and RKO cells. Oleandrin downregulated protein expression of pro-caspase-3, -9, but enhanced caspase-3, -9 activities. These effects were accompanied by upregulation of protein expression of cytochrome C and BAX, and downregulation of BCL-2 protein expression in a concentration-dependent manner. Furthermore, oleandrin increased intracellular Ca2+ concentration, but decreased GSH concentration in the cells. The present results suggest that oleandrin induces apoptosis in human colorectal cancer cells via the mitochondrial pathway. Our findings provide new insight into the mechanism of anti-cancer property of oleandrin.

  1. Epigenetics and colorectal cancer.

    Science.gov (United States)

    Lao, Victoria Valinluck; Grady, William M

    2011-10-18

    Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide. It results from an accumulation of genetic and epigenetic changes in colon epithelial cells, which transforms them into adenocarcinomas. Over the past decade, major advances have been made in understanding cancer epigenetics, particularly regarding aberrant DNA methylation. Assessment of the colon cancer epigenome has revealed that virtually all CRCs have aberrantly methylated genes and that the average CRC methylome has hundreds to thousands of abnormally methylated genes. As with gene mutations in the cancer genome, a subset of these methylated genes, called driver genes, is presumed to have a functional role in CRC. The assessment of methylated genes in CRCs has also revealed a unique molecular subgroup of CRCs called CpG island methylator phenotype (CIMP) cancers; these tumors have a particularly high frequency of methylated genes. These advances in our understanding of aberrant methylation in CRC have led to epigenetic alterations being developed as clinical biomarkers for diagnostic, prognostic and therapeutic applications. Progress in this field suggests that these epigenetic alterations will be commonly used in the near future to direct the prevention and treatment of CRC.

  2. Selective AKT Inhibition by MK-2206 Represses Colorectal Cancer-Initiating Stem Cells.

    Science.gov (United States)

    Malkomes, Patrizia; Lunger, Ilaria; Luetticke, Alexander; Oppermann, Elsie; Haetscher, Nadine; Serve, Hubert; Holzer, Katharina; Bechstein, Wolf Otto; Rieger, Michael A

    2016-09-01

    Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. Growing evidence indicates that tumor-initiating cells (TICs) are responsible for tumor growth and progression. Conventional chemotherapeutics do not sufficiently eliminate TICs, leading to tumor relapse. We aimed to gain insight into TIC biology by comparing the transcriptome of primary TIC cultures and their normal stem cell counterparts to uncover expression differences. We established colonosphere cultures derived from the resection of paired specimens of primary tumor and normal mucosa in patients with CRC. These colonospheres, enriched for TICs, were used for differential transcriptome analyses to detect new targets for a TIC-directed therapy. Effects of target inhibition on CRC cells were studied in vitro and in vivo. Pathway analysis of the regulated genes showed enrichment of genes central to PI3K/AKT and Wnt-signaling. We identified CD133 as a marker for a more aggressive CRC subpopulation enriched with TICs in SW480 CRC cells in an in vivo cancer model. Treatment of CRC cells with the selective AKT inhibitor MK-2206 caused a decrease in cell proliferation, particularly in the TIC fraction, resulting in a significant reduction of the stemness capacity to form colonospheres in vitro and to initiate tumor formation in vivo. Consequently, MK-2206 treatment of mice with established xenograft tumors exhibited a significant deceleration of tumor progression. Primary patient-derived tumorsphere growth was significantly inhibited by MK-2206. This study reveals that AKT signaling is critical for TIC proliferation and can be efficiently targeted by MK-2206 representing a preclinical therapeutic strategy to repress colorectal TICs.

  3. [Hereditary and familial colorectal cancer].

    Science.gov (United States)

    Balaguer, Francesc

    2014-09-01

    Up to 5% of all colorectal cancer cases are caused by a known hereditary syndrome. These hereditary types often need a higher degree of clinical suspicion to be diagnosed and require specific and specialized management. In addition, diagnosing hereditary colorectal cancer has significant consequences not only for the patient, for whom there are effective preventative measures, but also for their families, who could be carriers of the condition. The most significant advances in the field of colorectal cancer have come from the diagnosis and characterization of these syndromes. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  4. Colorectal cancer statistics, 2017.

    Science.gov (United States)

    Siegel, Rebecca L; Miller, Kimberly D; Fedewa, Stacey A; Ahnen, Dennis J; Meester, Reinier G S; Barzi, Afsaneh; Jemal, Ahmedin

    2017-05-06

    Colorectal cancer (CRC) is one of the most common malignancies in the United States. Every 3 years, the American Cancer Society provides an update of CRC incidence, survival, and mortality rates and trends. Incidence data through 2013 were provided by the Surveillance, Epidemiology, and End Results program, the National Program of Cancer Registries, and the North American Association of Central Cancer Registries. Mortality data through 2014 were provided by the National Center for Health Statistics. CRC incidence rates are highest in Alaska Natives and blacks and lowest in Asian/Pacific Islanders, and they are 30% to 40% higher in men than in women. Recent temporal patterns are generally similar by race and sex, but differ by age. Between 2000 and 2013, incidence rates in adults aged ≥50 years declined by 32%, with the drop largest for distal tumors in people aged ≥65 years (incidence rate ratio [IRR], 0.50; 95% confidence interval [95% CI], 0.48-0.52) and smallest for rectal tumors in ages 50 to 64 years (male IRR, 0.91; 95% CI, 0.85-0.96; female IRR, 1.00; 95% CI, 0.93-1.08). Overall CRC incidence in individuals ages ≥50 years declined from 2009 to 2013 in every state except Arkansas, with the decrease exceeding 5% annually in 7 states; however, rectal tumor incidence in those ages 50 to 64 years was stable in most states. Among adults aged history of CRC/advanced adenomas) and eliminating disparities in high-quality treatment. In addition, research is needed to elucidate causes for increasing CRC in young adults. CA Cancer J Clin 2017. © 2017 American Cancer Society. CA Cancer J Clin 2017;67:177-193. © 2017 American Cancer Society. © 2017 American Cancer Society.

  5. Danish Colorectal Cancer Group Database

    DEFF Research Database (Denmark)

    Ingeholm, Peter; Gögenur, Ismail; Iversen, Lene H

    2016-01-01

    AIM OF DATABASE: The aim of the database, which has existed for registration of all patients with colorectal cancer in Denmark since 2001, is to improve the prognosis for this patient group. STUDY POPULATION: All Danish patients with newly diagnosed colorectal cancer who are either diagnosed......, and other pathological risk factors. DESCRIPTIVE DATA: The database has had >95% completeness in including patients with colorectal adenocarcinoma with >54,000 patients registered so far with approximately one-third rectal cancers and two-third colon cancers and an overrepresentation of men among rectal...... diagnosis, surgical interventions, and short-term outcomes. The database does not have high-resolution oncological data and does not register recurrences after primary surgery. The Danish Colorectal Cancer Group provides high-quality data and has been documenting an increase in short- and long...

  6. Tumor-derived CXCL5 promotes human colorectal cancer metastasis through activation of the ERK/Elk-1/Snail and AKT/GSK3β/β-catenin pathways.

    Science.gov (United States)

    Zhao, Jingkun; Ou, Baochi; Han, Dingpei; Wang, Puxiongzhi; Zong, Yaping; Zhu, Congcong; Liu, Di; Zheng, Minhua; Sun, Jing; Feng, Hao; Lu, Aiguo

    2017-03-29

    Metastasis is a major cause of death in human colorectal cancer patients. However, the contribution of chemokines in the tumor microenvironment to tumor metastasis is not fully understood. Herein, we examinined several chemokines in colorectal cancer patients using chemokine ELISA array. Immunohistochemistry was used to detect expression of CXCL5 in colorectal cancer patients tissues. Human HCT116 and SW480 cell lines stably transfected with CXCL5, shCXCL5 and shCXCR2 lentivirus plasmids were used in our in vitro study. Immunoblot, immunofluorescence and transwell assay were used to examine the molecular biology and morphological changes in these cells. In addition, we used nude mice to detect the influence of CXCL5 on tumor metastasis in vivo. We found that CXCL5 was overexpressed in tumor tissues and associated with advanced tumor stage as well as poor prognosis in colorectal cancer patients. We also demonstrated that CXCL5 was primarily expressed in the tumor cell cytoplasm and cell membranes, which may indicate that the CXCL5 was predominantly produced by cancer epithelial cells instead of fibroblasts in the tumor mesenchyme. Additionally, overexpression of CXCL5 enhanced the migration and invasion of colorectal cancer cells by inducing the epithelial-mesenchymal transition (EMT) through activation of the ERK/Elk-1/Snail pathway and the AKT/GSK3β/β-catenin pathway in a CXCR2-dependent manner. The silencing of Snail and β-catenin attenuated CXCL5/CXCR2-enhanced cell migration and invasion in vitro. The elevated expression of CXCL5 can also potentiate the metastasis of colorectal cancer cells to the liver in vivo in nude mice intrasplenic injection model. In conclusion, our findings support CXCL5 as a promoter of colorectal cancer metastasis and a predictor of poor clinical outcomes in colorectal cancer patients.

  7. Combined miRNA profiling and proteomics demonstrates that different miRNAs target a common set of proteins to promote colorectal cancer metastasis.

    Science.gov (United States)

    Torres, Sofía; Garcia-Palmero, Irene; Bartolomé, Rubén A; Fernandez-Aceñero, María Jesús; Molina, Elena; Calviño, Eva; Segura, Miguel F; Casal, J Ignacio

    2017-05-01

    The process of liver colonization in colorectal cancer remains poorly characterized. Here, we addressed the role of microRNA (miRNA) dysregulation in metastasis. We first compared miRNA expression profiles between colorectal cancer cell lines with different metastatic properties and then identified target proteins of the dysregulated miRNAs to establish their functions and prognostic value. We found that 38 miRNAs were differentially expressed between highly metastatic (KM12SM/SW620) and poorly metastatic (KM12C/SW480) cancer cell lines. After initial validation, we determined that three miRNAs (miR-424-3p, -503, and -1292) were overexpressed in metastatic colorectal cancer cell lines and human samples. Stable transduction of non-metastatic cells with each of the three miRNAs promoted metastatic properties in culture and increased liver colonization in vivo. Moreover, miR-424-3p and miR-1292 were associated with poor prognosis in human patients. A quantitative proteomic analysis of colorectal cancer cells transfected with miR-424-3p, miR-503, or miR-1292 identified alterations in 149, 129, or 121 proteins, respectively, with an extensive overlap of the target proteins of the three miRNAs. Importantly, down-regulation of two of these shared target proteins, CKB and UBA2, increased cell adhesion and proliferation in colorectal cancer cells. The capacity of distinct miRNAs to regulate the same mRNAs boosts the capacity of miRNAs to regulate cancer metastasis and underscores the necessity of targeting multiple miRNAs for effective cancer therapy. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  8. Colorectal Cancer: The Importance of Early Detection

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Colorectal Cancer The Importance of Early Detection Past Issues / Summer ... Cancer of the colon or rectum is called colorectal cancer. The colon and the rectum are part of ...

  9. [Colorectal cancer prevention by flavonoids].

    Science.gov (United States)

    Hoensch, Harald; Richling, Elke; Kruis, Wolfgang; Kirch, Wilhelm

    2010-08-01

    Valid, sustained and safe clinical means of colorectal cancer prevention are still lacking, but they are urgently needed to lower the incidence of colorectal cancer. Dietary factors and phytochemicals such as flavonoids play an important role for prevention. A selective search of the literature using PubMed was performed with the following key words: flavonoids, cancer, therapy, colorectal cancer focused on clinical queries. Results of clinical studies including the authors' own were compared. In vivo and in vitro studies with animals, cell cultures and subcellular components provide ample evidence for antimutagenic and anticarcinogenic effects of flavonoids as shown for multiple biological and molecular endpoints. Isoflavonoids in vitro have been shown to induce proliferation of breast cancer cells. Epidemiologic trials (cohort, case-control and cross-sectional studies) yielded inconsistent results for flavonoid protection. Systematic reviews and meta-analyses support the protective role of tea flavonoids on adenoma incidence. An interventional pilot study with sustained flavonoid supplementation was shown to reduce the rate of neoplasia in patients with resected colorectal cancer. Selected flavonoids possess antimutagenic and anticarcinogenic properties and could reduce the incidence of colorectal neoplasias as shown in epidemiologic trials. Randomized controlled clinical studies with flavonoid intervention are necessary to provide evidence for their role in colorectal cancer prevention.

  10. Lyn is involved in CD24-induced ERK1/2 activation in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Su Ning

    2012-06-01

    Full Text Available Abstract Background and aim CD24 expression is associated with human colorectal cancer (CRC. Our previous data indicated that CD24 promoted the proliferation and invasion of colorectal cancer cells through the activation of ERK1/2. Since Src family kinases are frequently deregulated in CRC and closely related to the MAPK signaling pathway, we investigated the impact of Lyn, an important member of SFKs, on CD24-induced ERK1/2 activation in CRC. Methods and Results The interaction of CD24 and Lyn was identified by co-immunoprecipitation (Co-IP and ectopic expression of CD24-induced Lyn activation. Inhibition of Lyn activation by phosphatase PP2 in SW480CD24cells abrogated CD24-induced invasion. The results of the Co-IP and immunofluorescence assay revealed that overexpression of CD24 enhanced the interaction of Lyn and ERK1/2 and induced the nuclear translocation of Lyn. However, inhibition of Lyn activity attenuated CD24-induced ERK1/2 activation, and depletion of CD24 disrupted Lyn-ERK1/2 interaction. Immunohistochemistry analysis for 202 cases of CRC showed that the expression of both CD24 and Lyn was positively correlated with tumor grade, stage, lymph node and distant metastasis. Patients with lower expression of CD24 or Lyn had a higher survival rate. The Cox multivariate analysis showed that CD24 expression, but not Lyn expression, was an independent prognostic factor of CRC. Conclusions Our results suggest that Lyn is involved in CD24-induced ERK1/2 activation in CRC. The expression of CD24 is associated with activation of Lyn and ERK1/2, which might be a novel mechanism related to CD24-mediated regulation of CRC development.

  11. Lysyl oxidase in colorectal cancer

    DEFF Research Database (Denmark)

    Cox, Thomas R; Erler, Janine T

    2013-01-01

    Colorectal cancer is the third most prevalent form of cancer worldwide and fourth-leading cause of cancer-related mortality, leading to ~600,000 deaths annually, predominantly affecting the developed world. Lysyl oxidase is a secreted, extracellular matrix-modifying enzyme previously suggested...... to act as a tumor suppressor in colorectal cancer. However, emerging evidence has rapidly implicated lysyl oxidase in promoting metastasis of solid tumors and in particular colorectal cancer at multiple stages, affecting tumor cell proliferation, invasion, and angiogenesis. This emerging research has...... stimulated significant interest in lysyl oxidase as a strong candidate for developing and deploying inhibitors as functional efficacious cancer therapeutics. In this review, we discuss the rapidly expanding body of knowledge concerning lysyl oxidase in solid tumor progression, highlighting recent...

  12. Danish Colorectal Cancer Group Database

    DEFF Research Database (Denmark)

    Ingeholm, Peter; Gögenur, Ismail; Iversen, Lene H

    2016-01-01

    AIM OF DATABASE: The aim of the database, which has existed for registration of all patients with colorectal cancer in Denmark since 2001, is to improve the prognosis for this patient group. STUDY POPULATION: All Danish patients with newly diagnosed colorectal cancer who are either diagnosed......, and other pathological risk factors. DESCRIPTIVE DATA: The database has had >95% completeness in including patients with colorectal adenocarcinoma with >54,000 patients registered so far with approximately one-third rectal cancers and two-third colon cancers and an overrepresentation of men among rectal...... cancer patients. The stage distribution has been more or less constant until 2014 with a tendency toward a lower rate of stage IV and higher rate of stage I after introduction of the national screening program in 2014. The 30-day mortality rate after elective surgery has been reduced from >7% in 2001...

  13. Familial colorectal cancer type X

    DEFF Research Database (Denmark)

    Dominguez-Valentin, Mev; Therkildsen, Christina; Da Silva, Sabrina

    2015-01-01

    Heredity is a major cause of colorectal cancer, but although several rare high-risk syndromes have been linked to disease-predisposing mutations, the genetic mechanisms are undetermined in the majority of families suspected of hereditary cancer. We review the clinical presentation, histopathologi...... features, and the genetic and epigenetic profiles of the familial colorectal cancer type X (FCCTX) syndrome with the aim to delineate tumor characteristics that may contribute to refined diagnostics and optimized tumor prevention.......Heredity is a major cause of colorectal cancer, but although several rare high-risk syndromes have been linked to disease-predisposing mutations, the genetic mechanisms are undetermined in the majority of families suspected of hereditary cancer. We review the clinical presentation, histopathologic...

  14. [Prevention of colorectal cancer].

    Science.gov (United States)

    Gualdrini, Ubaldo Alfredo; Sambuelli, Alicia; Barugel, Mario; Gutiérrez, Alejandro; Avila, Karina Collia

    2005-01-01

    Colorectal cancer (CRC) is the second leading cause of cancer death in Argentina. The cumulative lifetime risk of developing CRC for both men and women is 4-6%. Despite advances in the management of this disease, the 5-year survival rate is about 60% because only 35% of patients are diagnosed when the disease is localized. Risk factors for CRC include age, diet and life style factors, personal or family history of adenomas or CRC and personal history of inflammatory bowel disease. Scientific evidence shows that primary and secondary prevention, through screening programs, permit to reduce incidence and mortality significantly. Chemopreventive agents, including nonsteroidal antiinflammatory drugs, folate, and calcium, have been shown to have some preventive effect. Physical inactivity and excess body weight are consistent risk factors for CRC. Tobacco exposure, diet high in red meat and low in vegetables and alcohol consumption, probably in combination with a diet low in folate, appear to increase risk. The dietary fiber and risk of CRC has been studied but the results are still inconclusive. Screening for CRC is cost-effective compared with no screening, but a single optimal strategy cannot be determined from the currently available data. The advantages and disadvantages or limitations of screening modalities for CRC are analyzed. The literature and clinical practice guidelines are reviewed, with an emphasis on advances and evolving screening methods and recommendations for patients with average, moderate and high-risk CRC.

  15. Molecular biology in colorectal cancer.

    Science.gov (United States)

    Benito, Manuel; Díaz-Rubio, Eduardo

    2006-06-01

    Cancer is a genetic disease. Colorectal cancer is probably the type of cancer for which the most is known about the genes affected by cancer-causing mutations, their normal functions and their carcinogenic effects when mutated. Most cancer-causing mutations are somatic, occurring in the affected tissue during the course of carcinogenesis. However, most cancers also have a hereditary component that is caused by predisposing mutations that affect the germline, are heritable and contribute to the initiation of carcinogenesis. High-penetrance mutations confer predisposition to colorectal cancer mainly in Lynch syndrome (which involves mutations in mismatch-repair genes) and in familial adenomatous polyposis (which involves mutations in the APC tumour suppressor). Together, these conditions account for 5% or less of all cases of colorectal cancer. Low-penetrance mutations account for a high proportion of all the attributable risk of colorectal cancer, in both familial and sporadic cases. These mutations are more difficult to identify, but mainly due to the implementation of association studies, are increasingly being detected and characterized. The identification of both high- and low-penetrance mutations contributes significantly to our understanding of the molecular genetic processes occurring in cancer. This understanding facilitates the development of therapeutic drugs and preventive strategies.

  16. Brain metastases from colorectal cancer

    DEFF Research Database (Denmark)

    Vagn-Hansen, Chris Aksel; Rafaelsen, Søren Rafael

    2001-01-01

    Brain metastases from colorectal cancer are rare. The prognosis for patients with even a single resectable brain metastasis is poor. A case of surgically treated cerebral metastasis from a rectal carcinoma is reported. The brain tumour was radically resected. However, cerebral, as well...... as extracerebral, disease recurred 12 months after diagnosis. Surgical removal of colorectal metastatic brain lesions in selected cases results in a longer survival time....

  17. Cost-effectiveness of colorectal cancer screening

    NARCIS (Netherlands)

    I. Lansdorp-Vogelaar (Iris); A.B. Knudsen (Amy); H. Brenner (Hermann)

    2011-01-01

    textabstractColorectal cancer is an important public health problem. Several screening methods have been shown to be effective in reducing colorectal cancer mortality. The objective of this review was to assess the cost-effectiveness of the different colorectal cancer screening methods and to

  18. Colorectal Cancer Awareness and Screening

    Centers for Disease Control (CDC) Podcasts

    2017-04-06

    An oncologist (cancer doctor) shares her medical and personal advice for people between the ages of 50 and 75 about getting screened for colorectal cancer.  Created: 4/6/2017 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 4/6/2017.

  19. Targeted nanoparticles for colorectal cancer

    DEFF Research Database (Denmark)

    Cisterna, Bruno A.; Kamaly, Nazila; Choi, Won Il

    2016-01-01

    Colorectal cancer (CRC) is highly prevalent worldwide, and despite notable progress in treatment still leads to significant morbidity and mortality. The use of nanoparticles as a drug delivery system has become one of the most promising strategies for cancer therapy. Targeted nanoparticles could...

  20. Colorectal Cancer Risk Prediction Models

    Science.gov (United States)

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

  1. Targeted nanoparticles for colorectal cancer

    DEFF Research Database (Denmark)

    Cisterna, Bruno A.; Kamaly, Nazila; Choi, Won Il

    2016-01-01

    Colorectal cancer (CRC) is highly prevalent worldwide, and despite notable progress in treatment still leads to significant morbidity and mortality. The use of nanoparticles as a drug delivery system has become one of the most promising strategies for cancer therapy. Targeted nanoparticles could ...

  2. Impact of the 3D microenvironment on phenotype, gene expression, and EGFR inhibition of colorectal cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Anna C Luca

    Full Text Available Three-dimensional (3D tumor cell cultures grown in laminin-rich-extracellular matrix (lrECM are considered to reflect human tumors more realistic as compared to cells grown as monolayer on plastic. Here, we systematically investigated the impact of ECM on phenotype, gene expression, EGFR signaling pathway, and on EGFR inhibition in commonly used colorectal cancer (CRC cell lines. LrECM on-top (3D culture assays were performed with the CRC cell lines SW-480, HT-29, DLD-1, LOVO, CACO-2, COLO-205 and COLO-206F. Morphology of lrECM cultivated CRC cell lines was determined by phase contrast and confocal laser scanning fluorescence microscopy. Proliferation of cells was examined by MTT assay, invasive capacity of the cell lines was assayed using Matrigel-coated Boyden chambers, and migratory activity was determined employing the Fence assay. Differential gene expression was analyzed at the transcriptional level by the Agilent array platform. EGFR was inhibited by using the specific small molecule inhibitor AG1478. A specific spheroid growth pattern was observed for all investigated CRC cell lines. DLD-1, HT-29 and SW-480 and CACO-2 exhibited a clear solid tumor cell formation, while LOVO, COLO-205 and COLO-206F were characterized by forming grape-like structures. Although the occurrence of a spheroid morphology did not correlate with an altered migratory, invasive, or proliferative capacity of CRC cell lines, gene expression was clearly altered in cells grown on lrECM as compared to 2D cultures. Interestingly, in KRAS wild-type cell lines, inhibition of EGFR was less effective in lrECM (3D cultures as compared to 2D cell cultures. Thus, comparing both 2D and 3D cell culture models, our data support the influence of the ECM on cancer growth. Compared to conventional 2D cell culture, the lrECM (3D cell culture model offers the opportunity to investigate permanent CRC cell lines under more physiological conditions, i.e. in the context of molecular

  3. Endothelial cells activate the cancer stem cell-associated NANOGP8 pathway in colorectal cancer cells in a paracrine fashion.

    Science.gov (United States)

    Wang, Rui; Bhattacharya, Rajat; Ye, Xiangcang; Fan, Fan; Boulbes, Delphine R; Xia, Ling; Ellis, Lee M

    2017-08-01

    In colorectal cancer (CRC), cancer stem cells (CSCs) have been hypothesized to mediate cell survival and chemoresistance. Previous studies from our laboratory described a role for liver parenchymal endothelial cells (LPECs) in mediating the CSC phenotype in CRC cells in a paracrine/angiocrine fashion. The objectives of this study were to determine whether endothelial cells (ECs) from different organs can induce the CSC phenotype in CRC cells and to elucidate the signaling pathways involved. We treated a newly developed CRC cell line (HCP-1) and established CRC cell lines (HT29 and SW480) with conditioned medium (CM) from primary ECs isolated from nonmalignant liver, lung, colon mucosa, and kidney. Our results showed that CM from ECs from all organs increased the number of CSCs, as determined by sphere formation, and protein levels of NANOG and OCT4 in CRC cells. With the focus of further elucidating the role of the liver vascular network in mediating the CSC phenotype, we demonstrated that CM from LPECs increased resistance to 5-fluorouracil in CRC cells. Moreover, we showed that LPEC CM specifically induced NANOGP8 expression in CRC cells by specific enzyme digestion and a luciferase reporter assay using a vector containing the NANOGP8 promoter. Lastly, we found that LPEC CM-induced NANOGP8 expression and sphere formation were mediated by AKT activation. Our studies demonstrated a paracrine role for ECs in regulating the CSC phenotype and chemoresistance in CRC cells by AKT-mediated induction of NANOGP8. These studies suggest a more specific approach to target CSCs by blocking the expression of NANOGP8 in cancer cells. © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

  4. Selective suicide gene therapy of colon cancer exploiting the urokinase plasminogen activator receptor promoter.

    Science.gov (United States)

    Teimoori-Toolabi, Ladan; Azadmanesh, Kayhan; Amanzadeh, Amir; Zeinali, Sirous

    2010-04-01

    Colon cancer is the third and fourth most prevalent cancer among Iranian men and women, respectively. Suicide gene therapy is one of the alternative therapeutic modalities for cancer. The application of specific promoters for therapeutic genes should decrease the adverse effects of this modality. The combined aims of this study were to design a specific suicide gene therapy construct for colon cancer and study its effect in distinct representatives of transformed and nontransformed cells. The KRAS oncogene signaling pathway is one of the most important signaling pathways activated in colon cancer; therefore, we inserted the urokinase plasminogen activator receptor (uPAR; PLAUR gene) promoter as one of the upregulated promoters by this pathway upstream of a suicide gene (thymidine kinase [TK]) and a reporter gene (beta-galactosidase, beta-gal [LacZ]). This promoter is a natural combination of different motifs responsive to the RAS signaling pathway, such as the transcription factors AP1 (FOS/JUN), SP1, SP3, and AP2alpha, and nuclear factor kappa B (NFkappaB). The reporter plasmid under the control of the uPAR promoter (PUCUPARLacZ) had the ability to express beta-gal in colon cancer cells (human colon adenocarcinoma [SW480] and human colorectal carcinoma [HCT116] cell lines), while it could not express beta-gal in nontransformed human umbilical vein endothelial cells (HUVEC) and normal colon cells. After confirming the ability of pUCUPARTK (suicide plasmid) to express TK in SW480 and HCT116 cells by real-time PCR, cytotoxicity assays showed that pUCUPARTK decreased the viability of these cells in the presence of ganciclovir 20 and 40 microg/mL (and higher), respectively. Although M30 CytoDEATH antibody could not detect a significant rate of apoptosis induced by ganciclovir in pUCUPARTK-transfected HCT116 cells, the percentage of stained cells was marked in comparison with untreated cells. While this antibody could detect apoptosis in HCT116 cell line transfected

  5. Genetic Testing for Hereditary Colorectal Cancer

    Science.gov (United States)

    ... Facebook Tweet Share Compartir Having a family health history of colorectal (colon) cancer can make you more likely to get colorectal ... Health History? If you have a family health history of colorectal cancer, your doctor may consider your family health history ...

  6. Growth-inhibitory effects of the chemopreventive agent indole-3-carbinol are increased in combination with the polyamine putrescine in the SW480 colon tumour cell line

    Directory of Open Access Journals (Sweden)

    Gescher Andreas

    2003-01-01

    Full Text Available Abstract Background Many tumours undergo disregulation of polyamine homeostasis and upregulation of ornithine decarboxylase (ODC activity, which can promote carcinogenesis. In animal models of colon carcinogenesis, inhibition of ODC activity by difluoromethylornithine (DFMO has been shown to reduce the number and size of colon adenomas and carcinomas. Indole-3-carbinol (I3C has shown promising chemopreventive activity against a range of human tumour cell types, but little is known about the effect of this agent on colon cell lines. Here, we investigated whether inhibition of ODC by I3C could contribute to a chemopreventive effect in colon cell lines. Methods Cell cycle progression and induction of apoptosis were assessed by flow cytometry. Ornithine decarboxylase activity was determined by liberation of CO2 from 14C-labelled substrate, and polyamine levels were measured by HPLC. Results I3C inhibited proliferation of the human colon tumour cell lines HT29 and SW480, and of the normal tissue-derived HCEC line, and at higher concentrations induced apoptosis in SW480 cells. The agent also caused a decrease in ODC activity in a dose-dependent manner. While administration of exogenous putrescine reversed the growth-inhibitory effect of DFMO, it did not reverse the growth-inhibition following an I3C treatment, and in the case of the SW480 cell line, the effect was actually enhanced. In this cell line, combination treatment caused a slight increase in the proportion of cells in the G2/M phase of the cell cycle, and increased the proportion of cells undergoing necrosis, but did not predispose cells to apoptosis. Indole-3-carbinol also caused an increase in intracellular spermine levels, which was not modulated by putrescine co-administration. Conclusion While indole-3-carbinol decreased ornithine decarboxylase activity in the colon cell lines, it appears unlikely that this constitutes a major mechanism by which the agent exerts its antiproliferative

  7. Growth-inhibitory effects of the chemopreventive agent indole-3-carbinol are increased in combination with the polyamine putrescine in the SW480 colon tumour cell line

    Science.gov (United States)

    Hudson, E Ann; Howells, Lynne M; Gallacher-Horley, Barbara; Fox, Louise H; Gescher, Andreas; Manson, Margaret M

    2003-01-01

    Background Many tumours undergo disregulation of polyamine homeostasis and upregulation of ornithine decarboxylase (ODC) activity, which can promote carcinogenesis. In animal models of colon carcinogenesis, inhibition of ODC activity by difluoromethylornithine (DFMO) has been shown to reduce the number and size of colon adenomas and carcinomas. Indole-3-carbinol (I3C) has shown promising chemopreventive activity against a range of human tumour cell types, but little is known about the effect of this agent on colon cell lines. Here, we investigated whether inhibition of ODC by I3C could contribute to a chemopreventive effect in colon cell lines. Methods Cell cycle progression and induction of apoptosis were assessed by flow cytometry. Ornithine decarboxylase activity was determined by liberation of CO2 from 14C-labelled substrate, and polyamine levels were measured by HPLC. Results I3C inhibited proliferation of the human colon tumour cell lines HT29 and SW480, and of the normal tissue-derived HCEC line, and at higher concentrations induced apoptosis in SW480 cells. The agent also caused a decrease in ODC activity in a dose-dependent manner. While administration of exogenous putrescine reversed the growth-inhibitory effect of DFMO, it did not reverse the growth-inhibition following an I3C treatment, and in the case of the SW480 cell line, the effect was actually enhanced. In this cell line, combination treatment caused a slight increase in the proportion of cells in the G2/M phase of the cell cycle, and increased the proportion of cells undergoing necrosis, but did not predispose cells to apoptosis. Indole-3-carbinol also caused an increase in intracellular spermine levels, which was not modulated by putrescine co-administration. Conclusion While indole-3-carbinol decreased ornithine decarboxylase activity in the colon cell lines, it appears unlikely that this constitutes a major mechanism by which the agent exerts its antiproliferative effect, although accumulation

  8. Nutrients, Foods, and Colorectal Cancer Prevention

    Science.gov (United States)

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

    2015-01-01

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

  9. Costs of Colorectal Cancer Screening

    Centers for Disease Control (CDC) Podcasts

    2017-04-04

    A health economist talks about studies on figuring out the costs of running a colorectal cancer screening program, and how this can lead to better screening.  Created: 4/4/2017 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 4/4/2017.

  10. Subnuclear proteomics in colorectal cancer

    DEFF Research Database (Denmark)

    Albrethsen, Jakob; Knol, Jaco C; Piersma, Sander R

    2010-01-01

    Abnormalities in nuclear phenotype and chromosome structure are key features of cancer cells. Investigation of the protein determinants of nuclear subfractions in cancer may yield molecular insights into aberrant chromosome function and chromatin organization and in addition may yield biomarkers...... for early cancer detection. Here we evaluate a proteomics work flow for profiling protein constituents in subnuclear domains in colorectal cancer tissues and apply this work flow to a comparative analysis of the nuclear matrix fraction in colorectal adenoma and carcinoma tissue samples. First, we...... established the reproducibility of the entire work flow. In a reproducibility analysis of three nuclear matrix fractions independently isolated from the same colon tumor homogenate, 889 of 1,047 proteins (85%) were reproducibly identified at high confidence (minimally two peptides per protein at 99...

  11. Immunotherapy for metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Ellebaek, Eva; Andersen, Mads Hald; Svane, Inge Marie

    2012-01-01

    Although no immunotherapeutic treatment is approved for colorectal cancer (CRC) patients, promising results from clinical trials suggest that several immunotherapeutic strategies may prove efficacious and applicable to this group of patients. This review describes the immunogenicity of CRC...... and presents the most interesting strategies investigated so far: cancer vaccination including antigen-defined vaccination and dendritic cell vaccination, chemo-immunotherapy, and adoptive cell transfer. Future treatment options as well as the possibility of combining existing therapies will be discussed along...

  12. Red meat and colorectal cancer

    OpenAIRE

    Nuri Faruk Aykan

    2015-01-01

    Colorectal cancer (CRC) is the third most common cancer in men and the second in women worldwide. More than half of cases occur in more developed countries. The consumption of red meat (beef, pork, lamb, veal, mutton) is high in developed countries and accumulated evidence until today demonstrated a convincing association between the intake of red meat and especially processed meat and CRC risk. In this review, meta-analyses of prospective epidemiological studies addressed to this association...

  13. Colorectal cancer family history assessment.

    Science.gov (United States)

    Kelly, Patricia Paul

    2011-10-01

    This article describes family history assessment for colorectal cancer in three outpatient gastroenterology units and examines gastroenterology unit nurses' knowledge and attitudes about family history assessments. Eighty-eight colonoscopy records were surveyed, and 16 RNs were interviewed. The medical record documentation was surveyed using a researcher-developed tool to identify type of cancer, age at disease onset, family relationship, and number of family members with cancer. Gastroenterology unit nurses were interviewed to assess knowledge and attitudes about family history assessment regarding colorectal cancer. Findings indicate that limited family history documentation was present in the medical record and that important age-at-disease-onset information was missing in 95% of patients with a family history of colorectal cancer and in 85% of patients with a family history of Lynch syndrome-associated cancers. No documentation was found in any charts about the number of affected relatives within the same family. Inconsistencies in family history documentation within the same medical record were noted, and family history information was found in multiple chart forms. Gastroenterology nurses rated family history as very important but gave a lower rating to personal knowledge about and resources for family history assessment.

  14. The Mendelian colorectal cancer syndromes.

    Science.gov (United States)

    Tomlinson, Ian

    2015-11-01

    A small minority of colorectal cancers (CRCs) (≤5%) are caused by a single, inherited faulty gene. These diseases, the Mendelian colorectal cancer (CRC) syndromes, have been central to our understanding of colorectal carcinogenesis in general. Most of the approximately 13 high-penetrance genes that predispose to CRC primarily predispose to colorectal polyps, and each gene is associated with a specific type of polyp, whether conventional adenomas (APC, MUTYH, POLE, POLD1, NTHL1), juvenile polyps (SMAD4, BMPR1A), Peutz-Jeghers hamartomas (LKB1/STK11) and mixed polyps of serrated and juvenile types (GREM1). Lynch syndrome (MSH2, MLH1, MSH6, PMS2), by contrast, is associated primarily with cancer risk. Major functional pathways are consistently inactivated in the Mendelian CRC syndromes: certain types of DNA repair (proofreading of DNA replication errors, mismatch repair and base excision repair) and signalling (bone morphogenetic protein (BMP), Wnt signalling and mTOR). The inheritance of the CRC syndromes also varies: most are dominant but some of the DNA repair deficiencies are recessive. Some of the Mendelian CRC genes are especially important because they play a role through somatic inactivation in sporadic CRC (APC, MLH1, SMAD4, POLE). Additional Mendelian CRC genes may remain to be discovered and searches for these genes are ongoing, especially in patients with multiple adenomas and hyperplastic polyps. © The Author(s) 2015.

  15. Danish Colorectal Cancer Group Database.

    Science.gov (United States)

    Ingeholm, Peter; Gögenur, Ismail; Iversen, Lene H

    2016-01-01

    The aim of the database, which has existed for registration of all patients with colorectal cancer in Denmark since 2001, is to improve the prognosis for this patient group. All Danish patients with newly diagnosed colorectal cancer who are either diagnosed or treated in a surgical department of a public Danish hospital. The database comprises an array of surgical, radiological, oncological, and pathological variables. The surgeons record data such as diagnostics performed, including type and results of radiological examinations, lifestyle factors, comorbidity and performance, treatment including the surgical procedure, urgency of surgery, and intra- and postoperative complications within 30 days after surgery. The pathologists record data such as tumor type, number of lymph nodes and metastatic lymph nodes, surgical margin status, and other pathological risk factors. The database has had >95% completeness in including patients with colorectal adenocarcinoma with >54,000 patients registered so far with approximately one-third rectal cancers and two-third colon cancers and an overrepresentation of men among rectal cancer patients. The stage distribution has been more or less constant until 2014 with a tendency toward a lower rate of stage IV and higher rate of stage I after introduction of the national screening program in 2014. The 30-day mortality rate after elective surgery has been reduced from >7% in 2001-2003 to database is a national population-based clinical database with high patient and data completeness for the perioperative period. The resolution of data is high for description of the patient at the time of diagnosis, including comorbidities, and for characterizing diagnosis, surgical interventions, and short-term outcomes. The database does not have high-resolution oncological data and does not register recurrences after primary surgery. The Danish Colorectal Cancer Group provides high-quality data and has been documenting an increase in short- and long

  16. Diallyl Disulfide (DADS), a Constituent of Garlic, Inactivates NF-κB and Prevents Colitis-Induced Colorectal Cancer by Inhibiting GSK-3β.

    Science.gov (United States)

    Saud, Shakir M; Li, Weidong; Gray, Zane; Matter, Matthias S; Colburn, Nancy H; Young, Matthew R; Kim, Young S

    2016-07-01

    There is a strong belief that garlic has medicinal properties and may even reduce the risk of developing certain cancers including those of the gastrointestinal tract. The chemopreventive effects of garlic may be attributed to the anti-inflammatory properties of the sulfur-containing constituents of garlic, which includes diallyl disulfide (DADS). Here, we demonstrate that DADS prevented colorectal tumorigenesis in a mouse model of colitis-induced colorectal cancer. Supplementation with 85 ppm of DADS (60 mg daily human equivalent dose) in the diet of FVB/N mice treated with chemical carcinogen azoxymethane (AOM) and colonic irritant dextran sodium sulfate (DSS) resulted in the reduction in tumor incidence, tumor number, and tumor burden by 21.54%, 47.3%, and 66.4%, respectively. Further analysis revealed that mice fed the DADS-supplemented diet resolved the initial DSS-induced inflammation faster than those on the control diet, preventing prolonged inflammation and cellular transformation. Subsequent mechanistic studies in vitro suggest that DADS chemopreventive effects are mediated through NF-κB signaling. When SW480 colorectal cancer cells were treated with DADS, NF-κB nuclear localization and activity were diminished. Interestingly, NF-κB suppression was found to be dependent on DADS inhibition of GSK-3β, a positive regulator of NF-κB. Inhibition of GSK-3β and loss of nuclear NF-κB activity were also observed in vivo in AOM/DSS-treated mice fed a diet supplemented with 85 ppm DADS. Our results indicate that DADS can prevent tumorigenesis by suppressing inflammation, a process largely involving GSK-3β inhibition and consequential reduction in NF-κB nuclear localization. Cancer Prev Res; 9(7); 607-15. ©2016 AACR. ©2016 American Association for Cancer Research.

  17. Microbial and viral pathogens in colorectal cancer.

    LENUS (Irish Health Repository)

    Collins, Danielle

    2012-02-01

    The heterogenetic and sporadic nature of colorectal cancer has led to many epidemiological associations with causes of this disease. As our understanding of the underlying molecular processes in colorectal-cancer develops, the concept of microbial-epithelial interactions as an oncogenic trigger might provide a plausible hypothesis for the pathogenesis of colorectal cancer. By contrast with other cancers of the gastrointestinal tract (gastric carcinoma, mucosa-associated lymphoid-tissue lymphoma), a direct causal link between microbial infection (bacteria and viruses) and colorectal carcinoma has not been established. Studies support the involvement of these organisms in oncogenesis, however, in colorectal cancer, clinical data are lacking. Here, we discuss current evidence (both in vitro and clinical studies), and focus on a putative role for bacterial and viral pathogens as a cause of colorectal cancer.

  18. Microbial and viral pathogens in colorectal cancer.

    LENUS (Irish Health Repository)

    Collins, Danielle

    2011-05-01

    The heterogenetic and sporadic nature of colorectal cancer has led to many epidemiological associations with causes of this disease. As our understanding of the underlying molecular processes in colorectal-cancer develops, the concept of microbial-epithelial interactions as an oncogenic trigger might provide a plausible hypothesis for the pathogenesis of colorectal cancer. By contrast with other cancers of the gastrointestinal tract (gastric carcinoma, mucosa-associated lymphoid-tissue lymphoma), a direct causal link between microbial infection (bacteria and viruses) and colorectal carcinoma has not been established. Studies support the involvement of these organisms in oncogenesis, however, in colorectal cancer, clinical data are lacking. Here, we discuss current evidence (both in vitro and clinical studies), and focus on a putative role for bacterial and viral pathogens as a cause of colorectal cancer.

  19. Role of detection of microsatellite instability in Chinese with hereditary nonpolyposis colorectal cancer or ordinary hereditary colorectal cancer

    OpenAIRE

    Liu, Wen-Zhi; Jin, Feng; ZHANG, ZHEN-HAI; Wang, Shu-Bao

    2006-01-01

    AIM: To detect microsatellite instability (MSI) in patients with hereditary nonpolyposis colorectal cancer or ordinary hereditary colorectal cancer and to provide criteria for screening the kindreds with hereditary nonpolyposis colorectal cancer at molecular level.

  20. Pregnane × Receptor (PXR expression in colorectal cancer cells restricts irinotecan chemosensitivity through enhanced SN-38 glucuronidation

    Directory of Open Access Journals (Sweden)

    Lumbroso Serge

    2010-03-01

    Full Text Available Abstract Background Clinical efficacy of chemotherapy in colorectal cancer is subjected to broad inter-individual variations leading to the inability to predict outcome and toxicity. The topoisomerase I inhibitor irinotecan (CPT-11 is worldwide approved for the treatment of metastatic colorectal cancer and undergoes extensive peripheral and tumoral metabolism. PXR is a xenoreceptor activated by many drugs and environmental compounds regulating the expression of drug metabolism and transport genes in detoxification organs such as liver and gastrointestinal tract. Considering the metabolic pathway of irinotecan and the tissue distribution of Pregnane × Receptor (PXR, we hypothesized that PXR could play a key role in colon cancer cell response to irinotecan. Results PXR mRNA expression was quantified by RT-quantitative PCR in a panel of 14 colon tumor samples and their matched normal tissues. PXR expression was modulated in human colorectal cancer cells LS174T, SW480 and SW620 by transfection and siRNA strategies. Cellular response to irinotecan and its active metabolic SN38 was assessed by cell viability assays, HPLC metabolic profiles and mRNA quantification of PXR target genes. We showed that PXR was strongly expressed in colon tumor samples and displayed a great variability of expression. Expression of hPXR in human colorectal cancer cells led to a marked chemoresistance to the active metabolite SN38 correlated with PXR expression level. Metabolic profiles of SN38 showed a strong enhancement of SN38 glucuronidation to the inactive SN38G metabolite in PXR-expressing cells, correlated with an increase of UDPglucuronosyl transferases UGT1A1, UGT1A9 and UGT1A10 mRNAs. Inhibition of PXR expression by lentivirus-mediated shRNA, led to SN38 chemoresistance reversion concomitantly to a decrease of UGT1A1 expression and SN38 glucuronidation. Similarly, PXR mRNA expression levels correlated to UGT1A subfamily expression in human colon tumor biopsies

  1. Microsatellite instability in colorectal cancer: clinicopathological significance

    National Research Council Canada - National Science Library

    Setaffy, Lisa; Langner, Cord

    2015-01-01

    Although often viewed as a single disease, colorectal cancer more accurately represents a constellation of heterogeneous subtypes that result from different combinations of genetic events and epigenetic alterations...

  2. Diagnostic Ultrasound in Colorectal Cancer

    DEFF Research Database (Denmark)

    Rafaelsen, Søren Rafael

    2014-01-01

    tumour stage and whether there is distant spread of the disease at the time of diagnosis. Ultrasound Diagnostics is non-unionized and less costly than MDCT, MRI and PET/CT. Although MRI in recent years has gained ground in diagnostics in Denmark, there are still patients who have contraindications to MRI...... or are non-compliant. Also, patient movement during the MRI sequence acquisition degrades image quality on MRI and decreases accuracy. Over the last years, the ultrasound technique has improved further by Power Doppler, intravenous contrast enhancement, and elastography. Ultrasound diagnostics has...... the potential to contribute to the staging of colorectal cancer. The purpose of these studies was to determine the usefulness of ultrasound diagnostics in patients with colorectal cancer.The purpose of the TRUS studies was to compare staging of rectal carcinomas using digital rectal exploration...

  3. Colorectal cancers and chlorinated water

    OpenAIRE

    El-Tawil, Ahmed Mahmoud

    2016-01-01

    Published reports have revealed increased risk of colorectal cancers in people exposed to chlorinated drinking water or chemical derivatives of chlorination. Oestrogen plays a dual positive functions for diminishing the possibilities of such risk by reducing the entrance, and increasing the excretion, of these chemicals. In addition, there are supplementary measures that could be employed in order to reduce this risk further, such as boiling the drinking water, revising the standard concentra...

  4. Dietary fiber, source foods and colorectal cancer risk: the Fukuoka Colorectal Cancer Study.

    Science.gov (United States)

    Uchida, Kazuhiro; Kono, Suminori; Yin, Guang; Toyomura, Kengo; Nagano, Jun; Mizoue, Tetsuya; Mibu, Ryuichi; Tanaka, Masao; Kakeji, Yoshihiro; Maehara, Yoshihiko; Okamura, Takeshi; Ikejiri, Koji; Futami, Kitaroh; Maekawa, Takafumi; Yasunami, Yohichi; Takenaka, Kenji; Ichimiya, Hitoshi; Terasaka, Reiji

    2010-10-01

    Despite much evidence from laboratory work, epidemiological evidence remains elusive regarding the role of dietary fiber in colorectal carcinogenesis. We investigated associations of dietary fiber and source foods with colorectal cancer risk in the Fukuoka Colorectal Cancer Study, a community-based case-control study. The study subjects were 816 incident cases of colorectal cancer and 815 community controls. Nutrient and food intakes were estimated on the basis of a computer-assisted interview regarding 148 dietary items. Odds ratios of colorectal cancer according to quintile categories of energy-adjusted intakes of dietary fiber and food groups were obtained with adjustment for non-dietary factors and dietary intakes of calcium and n-3 fatty acids. Total, soluble and insoluble dietary fibers were not measurably associated with overall risk or subsite-specific risk of colorectal cancer. By contrast, rice consumption was associated with a decreased risk of colorectal cancer (trend p = 0.03), particularly of distal colon and rectal cancer (trend p = 0.02), and high intake of non-rice cereals tended to be related to an increased risk of colon cancer (trend p = 0.07). There was no association between vegetable consumption and colorectal cancer, whereas individuals with the lowest intake of fruits tended to have an increased risk of colorectal cancer. The present study did not corroborate a protective association between dietary fiber and colorectal cancer, but suggested a decreased risk of distal colorectal cancer associated with rice consumption.

  5. Temperature induces significant changes in both glycolytic reserve and mitochondrial spare respiratory capacity in colorectal cancer cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Mitov, Mihail I., E-mail: m.mitov@uky.edu [Markey Cancer Center, University of Kentucky, Lexington, KY 40536 (United States); Harris, Jennifer W. [Department of Surgery, University of Kentucky, Lexington, KY 40506 (United States); Alstott, Michael C.; Zaytseva, Yekaterina Y. [Markey Cancer Center, University of Kentucky, Lexington, KY 40536 (United States); Evers, B. Mark [Markey Cancer Center, University of Kentucky, Lexington, KY 40536 (United States); Department of Surgery, University of Kentucky, Lexington, KY 40506 (United States); Butterfield, D. Allan [Markey Cancer Center, University of Kentucky, Lexington, KY 40536 (United States); Department of Chemistry, University of Kentucky, Lexington, KY 40506 (United States)

    2017-05-15

    Thermotherapy, as a method of treating cancer, has recently attracted considerable attention from basic and clinical investigators. A number of studies and clinical trials have shown that thermotherapy can be successfully used as a therapeutic approach for various cancers. However, the effects of temperature on cancer bioenergetics have not been studied in detail with a real time, microplate based, label-free detection approach. This study investigates how changes in temperature affect the bioenergetics characteristics (mitochondrial function and glycolysis) of three colorectal cancer (CRC) cell lines utilizing the Seahorse XF96 technology. Experiments were performed at 32 °C, 37 °C and 42 °C using assay medium conditions and equipment settings adjusted to produce equal oxygen and pH levels ubiquitously at the beginning of all experiments. The results suggest that temperature significantly changes multiple components of glycolytic and mitochondrial function of all cell lines tested. Under hypothermia conditions (32 °C), the extracellular acidification rates (ECAR) of CRC cells were significantly lower compared to the same basal ECAR levels measured at 37 °C. Mitochondrial stress test for SW480 cells at 37 °C vs 42 °C demonstrated increased proton leak while all other OCR components remained unchanged (similar results were detected also for the patient-derived xenograft cells Pt.93). Interestingly, the FCCP dose response at 37 °C vs 42 °C show significant shifts in profiles, suggesting that single dose FCCP experiments might not be sufficient to characterize the mitochondrial metabolic potential when comparing groups, conditions or treatments. These findings provide valuable insights for the metabolic and bioenergetic changes of CRC cells under hypo- and hyperthermia conditions that could potentially lead to development of better targeted and personalized strategies for patients undergoing combined thermotherapy with chemotherapy.

  6. Red Meat and Colorectal Cancer

    Science.gov (United States)

    2015-01-01

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

  7. Red meat and colorectal cancer

    Directory of Open Access Journals (Sweden)

    Nuri Faruk Aykan

    2015-12-01

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

  8. Red Meat and Colorectal Cancer.

    Science.gov (United States)

    Aykan, Nuri Faruk

    2015-02-10

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

  9. Colorectal Cancer Rates by Race and Ethnicity

    Science.gov (United States)

    ... Language: English (US) Español (Spanish) Recommend on Facebook Tweet Share Compartir The rate of people getting colorectal cancer or dying from colorectal cancer varies by race and ethnicity. Incidence Rates by Race/Ethnicity and Sex “Incidence rate” means how many people out of a given number ...

  10. Tailored Telephone Counseling Increases Colorectal Cancer Screening

    Science.gov (United States)

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

    2015-01-01

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

  11. Vitamin D, inflammation, and colorectal cancer progression

    NARCIS (Netherlands)

    Harten-Gerritsen, van Suzanne; Balvers, Michiel G.J.; Witkamp, Renger F.; Kampman, Ellen; Duijnhoven, van F.J.B.

    2015-01-01

    Survival from colorectal cancer is positively associated with vitamin D status. However, whether this association is causal remains unclear. Inflammatory processes may link vitamin D to colorectal cancer survival, and therefore investigating inflammatory markers as potential mediators may be a

  12. Indeterminate Pulmonary Nodules at Colorectal Cancer Staging

    DEFF Research Database (Denmark)

    Nordholm-Carstensen, Andreas; Wille-Jørgensen, Peer A; Jorgensen, Lars N

    2013-01-01

    This study aimed to estimate the prevalence of indeterminate pulmonary nodules and specific radiological and clinical characteristics that predict malignancy of these at initial staging chest computed tomography (CT) in patients with colorectal cancer. A considerable number of indeterminate...... pulmonary nodules, which cannot readily be classified as either benign or malignant, are detected at initial staging chest CT in colorectal cancer patients....

  13. Colorectal Cancer Awareness for Women via Facebook: A Pilot Study.

    Science.gov (United States)

    Brittain, Kelly; Pennings Kamp, Kendra J; Salaysay, Zachary

    Colorectal cancer is the third leading cause of cancer death among U.S. women. Women report being screened for colorectal cancer less often than men, and if colorectal cancer screening guidelines were routinely followed, approximately 60% of colorectal cancer deaths could be prevented. Many colorectal cancer screening interventions have not used Facebook, which is the most popular social media site among women. Little is known about engaging women in colorectal cancer screening and risk reduction information using Facebook. The "Colorectal Cancer Screening Awareness for Women" Facebook page was created to promote colorectal cancer screening and risk reduction awareness among women. Facebook posts targeted women aged 45-64 years and highlighted colorectal cancer screening methods, guidelines, and colorectal cancer risk reduction strategies. Demographics and data about the women's interactions with the page were collected using Facebook analytics and analyzed. The majority of the 391 users of the Colorectal Cancer Screening Awareness for Women Facebook page were women aged 45-54 years (56.5%). The most "liked" posts were related to colorectal cancer risk reduction behaviors. In an effort to increase routine colorectal cancer screening and colorectal cancer risk reduction behaviors, gastroenterology nurses and practices should consider Facebook as a good method to regularly engage women in colorectal cancer screening and colorectal cancer risk reduction information.

  14. [Burden of colorectal cancer in China].

    Science.gov (United States)

    Zhang, Yue; Shi, Jufang; Huang, Huiyao; Ren, Jiansong; Li, Ni; Dai, Min

    2015-07-01

    To understand the incidence and mortality of colorectal cancer in China. The data from GLOBOCAN 2012, Chinese Cancer Registry Annual Report 2012, Cancer Incidence in Five Continents (CI5), the Three National Death Cause Surveys in China and WHO Mortality Database were used to learn about the incidence and mortality of colorectal cancer and related trends in China. It was estimated by GLOBOCAN 2012 that in 2012 the age-standardized incidence of colorectal cancer in China was 16.9 per 100 000 in males and 11.6 per 100 000 in females, and the age-standardized mortality was 9.0 per 100 000 in males and 6.1 per 100 000 in females. GLOBOCAN 2012 estimated that colorectal cancer incidence and mortality would increase with the level of human development index. China's human development level was high, suggesting that the burden of colorectal cancer would be more serious in China with the development of social economy. The data from CI5 Volume IV and GLOBOCAN 2012 indicated that the incidence of colorectal cancer began to increase obviously at age of 50 years in China. Chinese Cancer Registry Annual Report 2012 showed that the incidence and mortality of colorectal cancer in urban population were two times higher than those in rural population in 2009, the proportions of colon cancer among colorectal and anus cancers, which was 49.0% in males and 54.2% in females, 53.4% in urban population and 41.7% in rural population. CI5 Volumes IV-X showed that colon cancer and rectum and anus cancer incidence in Shanghai for both males and females were increasing during the period 1973-2007. The percentage change in colon cancer and rectum and anus cancer incidence between 1973-1977 and 2003-2007 increased by 138.8% and 31.1% in males, 146.7% and 49.1% in females, respectively. The data from the Three National Death Cause Surveys showed that the crude mortality of colorectal cancer increased by 77.9% form mid 1970's (1973-1975) to mid 2000's (2004-2005). WHO Mortality Database showed

  15. Colorectal cancer cell-derived microvesicles are enriched in cell cycle-related mRNAs that promote proliferation of endothelial cells

    Directory of Open Access Journals (Sweden)

    Kim Yoon-Keun

    2009-11-01

    Full Text Available Abstract Background Various cancer cells, including those of colorectal cancer (CRC, release microvesicles (exosomes into surrounding tissues and peripheral circulation. These microvesicles can mediate communication between cells and affect various tumor-related processes in their target cells. Results We present potential roles of CRC cell-derived microvesicles in tumor progression via a global comparative microvesicular and cellular transcriptomic analysis of human SW480 CRC cells. We first identified 11,327 microvesicular mRNAs involved in tumorigenesis-related processes that reflect the physiology of donor CRC cells. We then found 241 mRNAs enriched in the microvesicles above donor cell levels, of which 27 were involved in cell cycle-related processes. Network analysis revealed that most of the cell cycle-related microvesicle-enriched mRNAs were associated with M-phase activities. The integration of two mRNA datasets showed that these M-phase-related mRNAs were differentially regulated across CRC patients, suggesting their potential roles in tumor progression. Finally, we experimentally verified the network-driven hypothesis by showing a significant increase in proliferation of endothelial cells treated with the microvesicles. Conclusion Our study demonstrates that CRC cell-derived microvesicles are enriched in cell cycle-related mRNAs that promote proliferation of endothelial cells, suggesting that microvesicles of cancer cells can be involved in tumor growth and metastasis by facilitating angiogenesis-related processes. This information will help elucidate the pathophysiological functions of tumor-derived microvesicles, and aid in the development of cancer diagnostics, including colorectal cancer.

  16. Electronic State of Sodium trans-[Tetrachloridobis(1H-indazole)ruthenate(III)] (NKP-1339) in Tumor, Liver and Kidney Tissue of a SW480-bearing Mouse

    Science.gov (United States)

    Blazevic, Amir; Hummer, Alfred A.; Heffeter, Petra; Berger, Walter; Filipits, Martin; Cibin, Giannantonio; Keppler, Bernhard K.; Rompel, Annette

    2017-01-01

    Ruthenium complexes are promising candidates for anticancer agents, especially NKP-1339 (sodium trans-[tetrachloridobis(1H-indazole)ruthenate(III)]), which is on the edge to clinical applications. The anticancer mechanism seems to be tightly linked to the redox chemistry but despite progress in human clinical trials the in vivo Ru oxidation state and the coordination of Ru remains unclear. The Ru-based anticancer drug NKP-1339 was studied applying XANES (Cl K- and Ru L2,3-edges) in tumor, kidney and liver tissue of a SW480 bearing mouse. Based on coordination charge and 3D XANES plots containing a series of model compounds as well as pre-edge analysis of the ligand Cl K-edge it is suggested that NKP-1339 remains in its +III oxidation state after 24 hours and at least one of the four chlorido ligands remain covalently bound to the Ru ion showing a biotransformation from RuIIIN2Cl4 to RuIIIClx(N/O)6-x (X = 1 or 2).

  17. Oncologic Management of Hereditary Colorectal Cancer

    OpenAIRE

    Yacoub, George; Nagalla, Srikanth; Aklilu, Mebea

    2012-01-01

    Colorectal cancer (CRC) is the second most common cancer in females and the third most common cancer diagnosed in males. Familial CRC comprises ~20 to 30% of all CRC cases. Lynch syndrome (LS), previously called hereditary nonpolyposis CRC (HNPCC), is the most common of the hereditary CRC syndromes. In this review, the oncological management of hereditary colorectal cancer from the medical oncologist perspective is discussed with special emphasis on Lynch syndrome. Lynch syndrome is character...

  18. Estrogen and colorectal cancer incidence and mortality.

    Science.gov (United States)

    Lavasani, Sayeh; Chlebowski, Rowan T; Prentice, Ross L; Kato, Ikuko; Wactawski-Wende, Jean; Johnson, Karen C; Young, Alicia; Rodabough, Rebecca; Hubbell, F Allan; Mahinbakht, Ali; Simon, Michael S

    2015-09-15

    The preponderance of observational studies describe an association between the use of estrogen alone and a lower incidence of colorectal cancer. In contrast, no difference in the incidence of colorectal cancer was seen in the Women's Health Initiative (WHI) randomized, placebo-controlled trial with estrogen alone after a mean intervention of 7.1 years and cumulative follow-up of 13.2 years. This study extends these findings by providing detailed analyses of the effects of estrogen alone on the histology, grade, and stage of colorectal cancer, relevant subgroups, and deaths from and after colorectal cancer. The WHI study was a randomized, double-blind, placebo-controlled trial involving 10,739 postmenopausal women with prior hysterectomy. Participants were assigned to conjugated equine estrogen at 0.625 mg/d (n = 5279) or a matching placebo (n = 5409). Rates of colorectal cancer diagnoses and deaths from and after colorectal cancer were assessed throughout the study. Colorectal cancer rates in the estrogen-alone and placebo groups were comparable: 0.14% and 0.12% per year, respectively (hazard ratio [HR], 1.13; 95% confidence interval [CI], 0.83-1.58; P = .43). Bowel screening examinations were comparable between the 2 groups throughout the study. The grade, stage, and location of colorectal cancer did not differ between the randomization groups. There were more colorectal cancer deaths in the estrogen-alone group (34 [0.05%] vs 24 [0.03%]; HR, 1.46, 95% CI, 0.86-2.46; P = .16), but the difference was not statistically significant. The colorectal cancer incidence was higher for participants with a history of colon polyp removal in the estrogen-alone group (0.23% vs 0.02%; HR, 13.47; nominal 95% CI, 1.76-103.0; P colorectal cancer or deaths from or after colorectal cancer. A possibly higher risk of colorectal cancer in women with prior colon polyp removal who use estrogen alone requires confirmation. © 2015 American Cancer Society.

  19. Wnt Signaling and Colorectal Cancer.

    Science.gov (United States)

    Schatoff, Emma M; Leach, Benjamin I; Dow, Lukas E

    2017-04-01

    The WNT signaling pathway is a critical mediator of tissue homeostasis and repair, and frequently co-opted during tumor development. Almost all colorectal cancers (CRC) demonstrate hyperactivation of the WNT pathway, which in many cases is believed to be the initiating and driving event. In this short review, we provide a focused overview of recent developments in our understanding of the WNT pathway in CRC, describe new research tools that are enabling a deeper understanding of WNT biology, and outline ongoing efforts to target this pathway therapeutically.

  20. Gene expression in colorectal cancer

    DEFF Research Database (Denmark)

    Birkenkamp-Demtroder, Karin; Christensen, Lise Lotte; Olesen, Sanne Harder

    2002-01-01

    Understanding molecular alterations in colorectal cancer (CRC) is needed to define new biomarkers and treatment targets. We used oligonucleotide microarrays to monitor gene expression of about 6,800 known genes and 35,000 expressed sequence tags (ESTs) on five pools (four to six samples in each......%). Fifteen nuclear encoded mitochondrial proteins were all down-regulated in CRC. We identified several chromosomal locations with clusters of either potential oncogenes or potential tumor suppressors. Some of these, such as aminopeptidase N/CD13 and sigma B3 protein on chromosome 15q25, coincided...

  1. Bifidobacterium Infantis Ameliorates Chemotherapy-Induced Intestinal Mucositis Via Regulating T Cell Immunity in Colorectal Cancer Rats

    Directory of Open Access Journals (Sweden)

    Hui Mi

    2017-08-01

    Full Text Available Background/Aims: Intestinal mucositis (IM is a commonly encountered side effect in cancer patients receiving chemotherapy. This study aimed to investigate the effect of Bifidobacterium infantis (B. infantis in attenuating the severity of chemotherapy-induced intestinal mucositis by regulating the T cell subsets in rats with colorectal cancer (CRC. Methods: Thirty male Sprague-Dawley (SD rats were injected dimethyl hydrazine (DMH subcutaneously for 10 weeks, and then injected SW480 cells in rectal mucosa to create a CRC model, and the rats were randomly divided into three groups: Control group (saline + saline, Chemotherapy group (saline + 5-FU+Oxaliplatin, B. infantis group (B. infantis + 5-FU+Oxaliplatin. IM was evaluated based on diarrhea severity, intestinal villus height, crypt depth, pro-inflammatory cytokines (IL-6, IL-1β, TNF-α, T cell subsets (CD4+ IL17A+ cells and CD4+ CD25+ Foxp3+ Tregs and related cytokine profiles. Results: The results showed that the B. infantis group demonstrated a higher body weight (BW and intestinal villus height and a deeper crypt depth compared to the Chemotherapy group. The level of IL-6, IL-1β and TNF-α which increased by chemotherapy, was lowered by B. infantis administration. Real time reverse transcription- polymerase chain reaction (RT-PCR showed B. infantis reduced relative expression of Th17 and Th1 cells related cytokines, and increased relative expression of CD4+ CD25+ Foxp3+ Tregs related cytokines. Furthermore, Flow cytometry analysis showed B. infantis reduced CD4+ IL17A+ cells and increased CD4+ CD25+ Foxp3+ Tregs in mesenteric lymph nodes (MLNs compared to the Chemotherapy group. Conclusion: B. infantis effectively attenuates chemotherapy-induced intestinal mucositis by decreasing Th1 and Th17 response and increasing CD4+ CD25+ Foxp3+ Tregs response.

  2. Long term transcriptional reactivation of epigenetically silenced genes in colorectal cancer cells requires DNA hypomethylation and histone acetylation.

    Directory of Open Access Journals (Sweden)

    David Mossman

    Full Text Available UNLABELLED: Epigenetic regulation of genes involves the coordination of DNA methylation and histone modifications to maintain transcriptional status. These two features are frequently disrupted in malignancy such that critical genes succumb to inactivation. 5-aza-2'-deoxycytidine (5-aza-dC is an agent which inhibits DNA methyltransferase, and holds great potential as a treatment for cancer, yet the extent of its effectiveness varies greatly between tumour types. Previous evidence suggests expression status after 5-aza-dC exposure cannot be explained by the DNA methylation status alone. AIM: We sought to identify chromatin changes involved with short and long term gene reactivation following 5-aza-dC exposure. Two colorectal cancer cell lines, HCT116 and SW480, were treated with 5-aza-dC and then grown in drug-free media to allow DNA re-methylation. DNA methylation and chromatin modifications were assessed with bisulfite sequencing and Chromatin Immuno-Precipitation analysis. RESULTS: Increased H3 acetylation, H3K4 tri-methylation and loss of H3K27 tri-methylation were associated with reactivation. Hypermethylated genes that did not show increased acetylation were transiently expressed with 5-aza-dC treatment before reverting to an inactive state. Three reactivated genes, CDO1, HSPC105 and MAGEA3, were still expressed 10 days post 5-aza-dC treatment and displayed localised hypomethylation at the transcriptional start site, and also an increased enrichment of histone H3 acetylation. CONCLUSIONS: These observations suggest that hypomethylation alone is insufficient to reactivate silenced genes and that increased Histone H3 acetylation in unison with localised hypomethylation allows long term reversion of these epigenetically silenced genes. This study suggests that combined DNA methyltransferase and histone deacetylase inhibitors may aid long term reactivation of silenced genes.

  3. Colorectal Cancer: Genetics is Changing Everything.

    Science.gov (United States)

    Obuch, Joshua C; Ahnen, Dennis J

    2016-09-01

    Cancer is fundamentally a genetic disease caused by mutational or epigenetic alterations in DNA. There has been a remarkable expansion of the molecular understanding of colonic carcinogenesis in the last 30 years and that understanding is changing many aspects of colorectal cancer care. It is becoming increasingly clear that there are genetic subsets of colorectal cancer that have different risk factors, prognosis, and response to treatment. This article provides a general update on colorectal cancer and highlights the ways that genetics is changing clinical care. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis

    NARCIS (Netherlands)

    Vasen, HFA; Wijnen, JT; Menko, FH; Kleibeuker, JH; Taal, BG; Griffioen, G; Nagengast, FM; MeijersHeijboer, EH; Bertario, L; Varesco, L; Bisgaard, ML; Mohr, J; Fodde, R; Khan, PM

    Background & Aims: Hereditary nonpolyposis colorectal cancer is characterized by early-onset colorectal cancer and the occurrence of various other cancers, The recent isolation of four mismatch repair genes responsible for hereditary nonpolyposis colorectal cancer allows for the identification of

  5. Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis

    NARCIS (Netherlands)

    Vasen, H. F.; Wijnen, J. T.; Menko, F. H.; Kleibeuker, J. H.; Taal, B. G.; Griffioen, G.; Nagengast, F. M.; Meijers-Heijboer, E. H.; Bertario, L.; Varesco, L.; Bisgaard, M. L.; Mohr, J.; Fodde, R.; Khan, P. M.

    1996-01-01

    Hereditary nonpolyposis colorectal cancer is characterized by early-onset colorectal cancer and the occurrence of various other cancers. The recent isolation of four mismatch repair genes responsible for hereditary nonpolyposis colorectal cancer allows for the identification of carriers within

  6. Examining racial disparities in colorectal cancer care.

    Science.gov (United States)

    Berry, Jamillah; Bumpers, Kevin; Ogunlade, Vickie; Glover, Roni; Davis, Sharon; Counts-Spriggs, Margaret; Kauh, John; Flowers, Christopher

    2009-01-01

    African Americans are disproportionately burdened with colorectal cancer. Although incidence and mortality rates have declined in the past two decades, the disparity in health outcomes has progressively increased. This comprehensive review examines the existing literature regarding racial disparities in colorectal cancer screening, stage at diagnosis, and treatment to determine if differences exist in the quality of care delivered to African Americans. A comprehensive review of relevant literature was performed. Two databases (EBSCOHOST Academic Search Premier and Scopus) were searched from 2000 to 2007. Articles that assessed racial disparities in colorectal cancer screening, stage of disease at diagnosis, and treatment were selected. The majority of studies identified examined colorectal cancer screening outcomes. Although racial disparities in screening have diminished in recent years, African American men and women continue to have higher colorectal cancer incidence and mortality rates and are diagnosed at more advanced stages. Several studies regarding stage of disease at diagnosis identified socioeconomic status (SES) and health insurance status as major determinants of disparity. However, some studies found significant racial disparities even after controlling for these factors. Racial disparities in treatment were also found at various diagnostic stages. Many factors affecting disparities between African Americans and Whites in colorectal cancer incidence and mortality remain unexplained. Although the importance of tumor biology, genetics, and lifestyle risk factors have been established, prime sociodemographic factors need further examination to understand variances in the care of African Americans diagnosed with colorectal cancer.

  7. Clinical management of hereditary colorectal cancer syndromes.

    Science.gov (United States)

    Vasen, Hans F A; Tomlinson, Ian; Castells, Antoni

    2015-02-01

    Hereditary factors are involved in the development of a substantial proportion of all cases of colorectal cancer. Inherited forms of colorectal cancer are usually subdivided into polyposis syndromes characterized by the development of multiple colorectal polyps and nonpolyposis syndromes characterized by the development of few or no polyps. Timely identification of hereditary colorectal cancer syndromes is vital because patient participation in early detection programmes prevents premature death due to cancer. Polyposis syndromes are fairly easy to recognize, but some patients might have characteristics that overlap with other clinically defined syndromes. Comprehensive analysis of the genes known to be associated with polyposis syndromes helps to establish the final diagnosis in these patients. Recognizing Lynch syndrome is more difficult than other polyposis syndromes owing to the absence of pathognomonic features. Most investigators therefore recommend performing systematic molecular analysis of all newly diagnosed colorectal cancer using immunohistochemical methods. The implementation in clinical practice of new high-throughput methods for molecular analysis might further increase the identification of individuals at risk of hereditary colorectal cancer. This Review describes the clinical management of the various hereditary colorectal cancer syndromes and demonstrates the advantage of using a classification based on the underlying gene defects.

  8. The Association Between Molecular Markers in Colorectal Sessile Serrated Polyps and Colorectal Cancer Risk

    Science.gov (United States)

    2017-08-01

    AWARD NUMBER: W81XWH-15-1-0273 TITLE: The Association between Molecular Markers in Colorectal Sessile Serrated Polyps and Colorectal Cancer ...Colorectal Cancer Risk 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-0273 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Andrea Burnett-Hartman 5d... cancer in patients with sessile serrated colorectal polyps (SSPs). The project’s specific aims are as follows: 1) Estimate the risk of colorectal

  9. [Colorectal cancer in the elderly].

    Science.gov (United States)

    Hoch, J; Bláha, M; Malúšková, D

    2016-01-01

    High incidence of colorectal cancer in the Czech Republic is an actual and demographically significant health issue. Half of all of the patients is older than 70 years. Both surgical and non-surgical treatment options in this group of patients depend on factors that are difficult to measure only by current oncological and anesthesiological classifications (cTcNcM, ASA). The objective of this paper is to measure the impact of age on the use of various treatment modalities within the protocol and their results, and also to suggest alternative options for therapy tolerance assessment. Analysis of data over a five-year period from the NOR database prepared by the Institute of Biostatistics and Analyses, Masaryk University. In all parameters a difference was demonstrated between patients below the age of 70 and those above the age of 70 years. Older patients were disadvantaged. Only 11.2% of patients younger than 70 years were not treated, whereas 25.2% over the age of 70 years were not treated. A complex geriatric examination could improve the indication process in various treatment modalities, including surgery. colorectal cancer - elderly - treatment - geriatric assesment.

  10. Tucatinib (ONT-380) and Trastuzumab in Treating Patients With HER2+ Metastatic Colorectal Cancer

    Science.gov (United States)

    2018-02-08

    Colorectal Adenocarcinoma; ERBB2 Gene Amplification; HER2/Neu Positive; KRAS wt Allele; NRAS wt Allele; Recurrent Colorectal Carcinoma; Stage III Colorectal Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IV Colorectal Cancer AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7

  11. Colorectal Cancer Screening in Asia.

    Science.gov (United States)

    Chiu, Han-Mo; Hsu, Wen-Feng; Chang, Li-Chun; Wu, Ming-Hsiang

    2017-08-10

    Colorectal cancer (CRC) is increasing in Asia, especially in regions with higher levels of economic development. Several Asian countries have launched population CRC screening programs to combat this devastating disease because previous studies have demonstrated that either fecal occult blood test or lower gastrointestinal endoscopy can effectively reduce CRC mortality. Screening includes engaging the population, testing, administering a confirmation examination, and treating screening-detected neoplasms; thus, monitoring the whole process using measurable indicators over time is of utmost importance. Only when the quality of every step is secured can the effectiveness of CRC screening be maximized. Screening and verification examination rates remain low in Asian countries, and important infrastructure, including cancer or death registry systems, colonoscopy capacity, and reasonable subsidization for screening, is lacking or insufficient. Future research should identify potential local barriers to screening. Good communication and dialog among screening organizers, clinicians, professional societies, and public health workers are indispensible for successful screening programs.

  12. Calcium remodeling in colorectal cancer.

    Science.gov (United States)

    Villalobos, Carlos; Sobradillo, Diego; Hernández-Morales, Miriam; Núñez, Lucía

    2017-06-01

    Colorectal cancer (CRC) is the third most frequent form of cancer and the fourth leading cause of cancer-related death in the world. Basic and clinical data indicate that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) may prevent colon cancer but mechanisms remain unknown. Aspirin metabolite salicylate and other NSAIDs may inhibit tumor cell growth acting on store-operated Ca(2+) entry (SOCE), suggesting an important role for this pathway in CRC. Consistently, SOCE is emerging as a novel player in different forms of cancer, including CRC. SOCE and store-operated currents (SOCs) are dramatically enhanced in CRC while Ca(2+) stores are partially empty in CRC cells. These features may contribute to CRC hallmarks including enhanced cell proliferation, migration, invasion and survival. At the molecular level, enhanced SOCE and depleted stores are mediated by overexpression of Orai1, Stromal interaction protein 1 (STIM1) and Transient receptor protein channel 1 (TRPC1) and downregulation of STIM2. In normal colonic cells, SOCE is mediated by Ca(2+)-release activated Ca(2+) channels made of STIM1, STIM2 and Orai1. In CRC cells, SOCE is mediated by different store-operated currents (SOCs) driven by STIM1, Orai1 and TRPC1. Loss of STIM2 contributes to depletion of Ca(2+) stores and enhanced resistance to cell death in CRC cells. Thus, SOCE is a novel key player in CRC and inhibition by salicylate and other NSAIDs may contribute to explain chemoprevention activity. Colorectal cancer (CRC) is the third most frequent form of cancer worldwide. Recent evidence suggests that intracellular Ca(2+) remodeling may contribute to cancer hallmarks. In addition, aspirin and other NSAIDs might prevent CRC acting on remodeled Ca(2+) entry pathways. In this review, we will briefly describe 1) the players involved in intracellular Ca(2+) homeostasis with a particular emphasis on the mechanisms involved in SOCE activation and inactivation, 2) the evidence that aspirin

  13. Colorectal Cancer Metastasis to the Thymus Gland: Rare Presentation of Colorectal Cancer as Anterior Mediastinal Mass

    OpenAIRE

    Peters, H. Charles; Liu, Xiuli; Iqbal, Atif; Cunningham, Lisa A.; Tan, Sanda A.

    2017-01-01

    Despite improved screening modalities, 15–25% of newly diagnosed colorectal cancers are metastatic at the time of diagnosis. The vast majority of these cases present as hepatic metastasis; however, 22% present with concomitant extrahepatic disease. The thymus gland is an uncommon site of metastasis for any primary malignancy, particularly, colorectal cancer given its vascular and lymphatic drainage. This case report details our experience with a rare case of colorectal cancer metastasis to th...

  14. Colorectal Cancer Metastasis to the Thymus Gland: Rare Presentation of Colorectal Cancer as Anterior Mediastinal Mass.

    Science.gov (United States)

    Peters, H Charles; Liu, Xiuli; Iqbal, Atif; Cunningham, Lisa A; Tan, Sanda A

    2017-01-01

    Despite improved screening modalities, 15-25% of newly diagnosed colorectal cancers are metastatic at the time of diagnosis. The vast majority of these cases present as hepatic metastasis; however, 22% present with concomitant extrahepatic disease. The thymus gland is an uncommon site of metastasis for any primary malignancy, particularly, colorectal cancer given its vascular and lymphatic drainage. This case report details our experience with a rare case of colorectal cancer metastasis to the thymus gland presenting as a symptomatic mediastinal mass.

  15. Nutrients, foods, and colorectal cancer prevention.

    Science.gov (United States)

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

    2015-05-01

    Diet has an important role in the development of colorectal cancer. In the past few decades, findings from extensive epidemiologic and experimental investigations have linked consumption of several foods and nutrients to the risk of colorectal neoplasia. Calcium, fiber, milk, and whole grains have been associated with a lower risk of colorectal cancer, and red meat and processed meat have been associated with an increased risk. There is substantial evidence for the potential chemopreventive effects of vitamin D, folate, fruits, and vegetables. Nutrients and foods also may interact, as a dietary pattern, to influence colorectal cancer risk. Diet likely influences colorectal carcinogenesis through several interacting mechanisms. These include the direct effects on immune responsiveness and inflammation, and the indirect effects of overnutrition and obesity-risk factors for colorectal cancer. Emerging evidence also implicates the gut microbiota as an important effector in the relationship between diet and cancer. Dietary modification therefore has the promise of reducing colorectal cancer incidence. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  16. IL-8 Is Involved in Estrogen-Related Receptor α-Regulated Proliferation and Migration of Colorectal Cancer Cells.

    Science.gov (United States)

    Ding, Sijuan; Tang, Zhaohui; Jiang, Yongjun; Huang, Honglin; Luo, Pengfei; Qing, Bohua; Zhang, Siyuan; Tang, Ruoting

    2017-10-09

    Studies revealed that estrogenic signals were involved in the development of colorectal cancer (CRC), while the roles of estrogen related receptor (ERR) on the progression of CRC have not been well illustrated. Its roles on the development of CRC were investigated. The expression of ERRα/β/γ in CRC cells were measured. The effects of ERRα on cell proliferation, migration and expression of cytokines were investigated accordingly. Our data revealed that the expression of ERRα, while not ERRβ or ERRγ, was significantly increased in CRC cells and clinical CRC tissues. Both the inverse agonist of ERRα (XCT-790) and si-ERRα can inhibit the proliferation of CRC cells. XCT-790 treatment can also suppress the wound healing and in vitro migration of CRC cells. Cytokine assays showed that XCT-790 can significantly decrease the expression of interleukin-8 (IL-8), while not IL-4, IL-6, IL-8, IL-9, IL-10, IL-18, IFN-γ, or TGF-β, in CRC cells. Over expression of ERRα increased the expression of IL-8. Luciferase assay showed XCT-790 decreased the promoter activity of IL-8. XCT-790 can increase the decay of IL-8 mRNA in SW480 cells. The recombinant IL-8 (rIL-8) can rescue XCT-790 induced suppression of proliferation and migration of CRC cells. XCT-790 can decrease the phosphorylation of ERK1/2 and STAT3, two downstream signal molecules of IL-8, in CRC cells. While rIL-8 can markedly attenuate XCT-790 induced dephosphorylation of ERK1/2 and STAT3. Our data showed that ERRα can trigger the proliferation and migration of CRC cells via up regulation of IL-8. Therefor targeted inhibition of ERRα/IL-8 might be a potential approach for CRC treatment and drug development.

  17. Pathological and biological aspects of colorectal cancer treatment

    NARCIS (Netherlands)

    Gosens, Marleen Johanna Elisabeth Maria

    2008-01-01

    Pathological and biological aspects of colorectal cancer treatment. This thesis describes several pathological and biological aspects of colorectal cancer treatment. Different patient populations were investigated including patients with mobile rectal cancer enrolled in the Dutch TME trial, patients

  18. Gastrins, iron and colorectal cancer.

    Science.gov (United States)

    Baldwin, Graham S

    2009-09-01

    This minireview explores the connections between circulating gastrins, iron status and colorectal cancer. The peptide hormone gastrin is a major regulator of acid secretion and a potent mitogen for normal and malignant gastrointestinal cells. Gastrins bind two ferric ions with μM affinity and, in the case of non-amidated forms of the hormone, iron binding is essential for biological activity. The ferric ion ligands have been identified as glutamates 7, 8 and 9 in the 18 amino acid peptide glycine-extended gastrin. An interaction between gastrin and transferrin was first demonstrated by covalent crosslinking techniques, and has been recently confirmed by surface plasmon resonance. We have therefore proposed that gastrins act as catalysts in the loading of transferrin with iron. Several recent lines of evidence, including the facts that the concentrations of circulating gastrins are increased in mice and humans with the iron overload disease haemochromatosis, and that transferrin saturation positively correlates with circulating gastrin concentrations, suggest that gastrins may be involved in iron homeostasis. In addition the recognition that ferric ions may play an unexpected role in the biological activity of non-amidated gastrins may assist in the development of new therapies for colorectal carcinoma.

  19. Familial Colorectal Cancer: Understanding the Alphabet Soup.

    Science.gov (United States)

    Giglia, Matthew D; Chu, Daniel I

    2016-09-01

    While most colorectal cancers (CRCs) originate from nonhereditary spontaneous mutations, one-third of cases are familial or hereditary. Hereditary CRCs, which account for alphabet soup of genes to provide the highest quality of care for patients and families.

  20. Diagnostic Approach to Hereditary Colorectal Cancer Syndromes

    Science.gov (United States)

    Kalady, Matthew F.; Heald, Brandie

    2015-01-01

    Approximately 5 to 10% of colorectal cancers develop within a known hereditary syndrome. Specific underlying genetic mutations drive the clinical phenotype and it is imperative to determine the genetic etiology to provide meaningful surveillance and intervention. Recognizing potential patients and families with a hereditary predisposition is the first step in management. Syndromes can be categorized according to polyp burden as polyposis or nonpolyposis. Clinical assessment should start with a personal and family medical history, physical examination, and evaluation for the presence and type of colorectal polyps or cancers. Key information is gained from these simple steps and should guide the specific genetic analysis for diagnosis. Genetic counseling is a critical component to any hereditary colorectal cancer program and should be conducted before genetic testing to provide education about the implications of test results. This review focuses on the thought process that drives initial clinical evaluation and guides genetic testing for patients with suspected hereditary colorectal cancer syndromes. PMID:26664327

  1. 5-FU Based Maintenance Therapy in RAS Wild Type Metastatic Colorectal Cancer After Induction With FOLFOX Plus Panitumumab

    Science.gov (United States)

    2017-10-17

    Colorectal Adenocarcinoma; RAS Wild Type; Stage III Colorectal Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IV Colorectal Cancer AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7

  2. Ranitidine as adjuvant treatment in colorectal cancer

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Christensen, Ib Jarle; Moesgaard, F

    2002-01-01

    BACKGROUND: Results from short-term studies of histamine type 2 (H2) receptor antagonists on survival of patients with solid tumours are debatable. In this study the efficacy of the H2-receptor antagonist ranitidine on long-term survival of patients with colorectal cancer was evaluated. METHODS...... curative resection of colorectal cancer and who do not receive perioperative blood transfusion and do not develop postoperative infectious complications....

  3. Precancerous Lesions in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Fayez Sandouk

    2013-01-01

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

  4. Hereditary Colorectal Cancer : Genetics and Screening

    NARCIS (Netherlands)

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

    2015-01-01

    Colorectal cancer (CRC) is the third most common cancer and the third leading cause of cancer death in men and women in the United States. About 30% of patients with CRC report a family history of CRC. However, only 5% of CRCs arise in the setting of a well-established mendelian inherited disorder.

  5. Epigenetic prognostic biomarkers in colorectal cancer

    NARCIS (Netherlands)

    Benard, Anne

    2015-01-01

    Colorectal cancer is one of the most common diagnosed cancers worldwide, and is the second most important cause of cancer mortality in Europe. The current TNM staging system used at the time of diagnosis is insufficient, as patients with the same tumor stage show wide variations in survival and

  6. Gynecologic screening in hereditary nonpolyposis colorectal cancer

    NARCIS (Netherlands)

    Rijcken, FEM; Mourits, MJE; Kleibeuker, JH; Hollema, H; van der Zee, AGJ

    2003-01-01

    Objective. In hereditary nonpolyposis colorectal cancer (HNPCC), women with a mismatch repair (MMR) gene mutation have a cumulative lifetime risk of 25-50% for endometrial cancer and 8-12% for ovarian cancer. Therefore, female members of HNPCC families are offered an annual gynecologic and

  7. Survival of MUTYH-associated polyposis patients with colorectal cancer and matched control colorectal cancer patients

    NARCIS (Netherlands)

    M. Nielsen (Maartje); L.N. van Steenbergen (Liza); N. Jones (Natalie); S. Vogt (Stefanie); H.F. Vasen (Hans); H. Morreau (Hans); S. Aretz (Stefan); J. Sampson (Julian); O.M. Dekkers (Olaf); M.L.G. Janssen-Heijnen (Maryska); F.J. Hes (Frederik)

    2010-01-01

    textabstractBackground MUTYH-associated polyposis is a recessively inherited disorder characterized by a lifetime risk of colorectal cancer that is up to 100%. Because specific histological and molecular genetic features of MUTYH-associated polyposis colorectal cancers might influence tumor behavior

  8. Colorectal Cancer - What You Need to Know

    Centers for Disease Control (CDC) Podcasts

    2011-07-05

    This podcast is based on the July, 2011 CDC Vital Signs report. Colorectal cancer kills about 50,000 men and women every year. Screening can save lives! Screening can find abnormal growths so they can be removed before turning into cancer, and can find the cancer early, when it's easiest to treat. If you're over 50, talk to your doctor about getting screened for colorectal cancer.  Created: 7/5/2011 by Centers for Disease Control and Prevention (CDC).   Date Released: 7/5/2011.

  9. Epigenetics and Colorectal Cancer Pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Bardhan, Kankana; Liu, Kebin, E-mail: Kliu@gru.edu [Department of Biochemistry and Molecular Biology, Medical College of Georgia, and Cancer Center, Georgia Regents University, Augusta, GA 30912 (United States)

    2013-06-05

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

  10. Identification of Novel Biomarkers for Metastatic Colorectal Cancer Using Angiogenesis-Antibody Array and Intracellular Signaling Array.

    Directory of Open Access Journals (Sweden)

    Seyung Chung

    Full Text Available Colorectal cancer (CRC is one of the three leading causes for cancer mortality. CRC kills over 600,000 people annually worldwide. The most common cause of death from CRC is the metastasis to distant organs. However, biomarkers for CRC metastasis remain ill-defined. We compared primary and metastatic CRC cell lines for their angiogenesis-protein profiles and intracellular signaling profiles to identify novel biomarkers for CRC metastasis. To this end, we used primary and metastatic CRC cell lines as a model system and normal human colon cell line as a control. The angiogenesis profiles two isogenic CRC cell lines, SW480 and SW620, and HT-29 and T84 revealed that VEGF was upregulated in both SW620 and T84 whereas coagulation factor III, IGFBP-3, DPP IV, PDGF AA/AB, endothelin I and CXCL16 were downregulated specifically in metastatic cell lines. Furthermore, we found that TIMP-1, amphiregulin, endostatin, angiogenin were upregulated in SW620 whereas downregulated in T84. Angiogenin was downregulated in T84 and GM-CSF was also downregulated in SW620. To induce CRC cell metastasis, we treated cells with pro-inflammatory cytokine IL-6. Upon IL-6 treatment, epithelial-mesenchymal transition was induced in CRC cells. When DLD-1 and HT-29 cells were treated with IL-6; Akt, STAT3, AMPKα and Bad phosphorylation levels were increased. Interestingly, SW620 showed the same signal activation pattern with IL-6 treatment of HT-29 and DLD-1. Our data suggest that Akt, STAT3, AMPKα and Bad activation can be biomarkers for metastatic colorectal cancer. IL-6 treatment specifically reduced phosphorylation levels of EGFR, HER2 receptor, Insulin R and IGF-1R in receptor tyrosine kinase array study with HT-29. Taken together, we have identified novel biomarkers for metastatic CRC through the angiogenesis-antibody array and intracellular signaling array studies. Present study suggests that those novel biomarkers can be used as CRC prognosis biomarkers, and as

  11. Adipokines linking obesity with colorectal cancer risk in postmenopausal women

    National Research Council Canada - National Science Library

    Ho, Gloria Y F; Wang, Tao; Gunter, Marc J; Strickler, Howard D; Cushman, Mary; Kaplan, Robert C; Wassertheil-Smoller, Sylvia; Xue, Xiaonan; Rajpathak, Swapnil N; Chlebowski, Rowan T; Vitolins, Mara Z; Scherer, Philipp E; Rohan, Thomas E

    2012-01-01

    Mechanistic associations between obesity and colorectal cancer remain unclear. In this study, we investigated whether adipokines are risk factors for colorectal cancer and whether they may mediate its association with obesity...

  12. Dietary folate and APC mutations in sporadic colorectal cancer

    NARCIS (Netherlands)

    Vogel, S. de; Engeland, M. van; Lüchtenborg, M.; Bruïne, A.P. de; Roemen, G.M.J.M.; Lentjes, M.H.F.M.; Goldbohm, R.A.; Brandt, P.A. van den; Goeij, A.F.P.M. de; Weijenberg, M.P.

    2006-01-01

    Folate deficiency has been associated with colorectal cancer risk and may be involved in colorectal carcinogenesis through increased chromosome instability, gene mutations, and aberrant DNA methylation. Within the Netherlands Cohort Study on diet and cancer, we investigated the associations between

  13. Frequently Asked Questions about Colorectal Cancer and IBD

    Science.gov (United States)

    ... IBD Go Back Frequently Asked Questions About Colorectal Cancer & IBD Email Print + Share CCFA's Chair of Professional Education, Tom Ullman, MD, Answers Frequently Asked Questions About Colorectal Cancer & IBD Each year, in the United States, 147, ...

  14. Colorectal Cancer Mortality in Shiraz, Iran.

    Science.gov (United States)

    Dianatinasab, Mostafa; Ghaem, Haleh; Rezaianzadeh, Abbas; Hosseini, Seysd Vahid; Khazraei, Hajar

    2016-01-01

    Mortality among Iranian patients with colorectal cancer has not been fully examined and the factors associated with their survival are still controversial. This study aimed to determine the mortality rate and its related factors among the patients with colorectal cancer in southwestern regions in Iran. This prospective cohort study was conducted on 220 patients with colorectal cancer referred to Fahighi Hospital, Shiraz, Iran from 2009 to 2014. Data were collected from the patients' medical records and were analyzed using Cox regression analysis. Over a median follow-up of 29.3 months, 56 out of the 220 patients (25.5%) died, 32 (14.5%) aged below 40 years, and 45.5% were female. Based on the results of multiple Cox regression analysis, family history of gastrointestinal cancer, stage III, former smoking, type of lesion (fungative and polypoid), and opium use were associated with a greater risk of colorectal cancer mortality (all <0.05). This cohort study found that the mortality rate of colorectal cancer in Iran is lower than that in European countries. In addition, behavioral and clinical factors were significantly associated with the survival rate. Addressing the related factors would help healthcare providers and physicians provide the best care and improve the survival rate.

  15. Cytogenetic findings in metastases from colorectal cancer

    DEFF Research Database (Denmark)

    Bardi, G; Parada, L A; Bomme, L

    1997-01-01

    Eighteen tumor samples from 11 patients with metastatic colorectal cancer were cytogenetically analyzed after short-term culturing. Of the 13 metastases examined, 11 were from lymph nodes, 1 from the peritoneum and 1 from the lung. In 5 of the 11 patients, matched samples from the primary tumor...... colorectal carcinomas, and del(10)(q22) and add(16)(p13), which so far have not been associated with primary tumors and which may play a particular pathogenetic role in the metastatic process....

  16. Tissue Specific Promoters in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    A. R. Rama

    2015-01-01

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

  17. Ziv-aflibercept in metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Patel A

    2013-12-01

    Full Text Available Anuj Patel, Weijing Sun Division of Hematology-Oncology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Abstract: The combination of cytotoxic chemotherapy and antiangiogenic agents has become a conventional treatment option for patients with metastatic colorectal cancer. Ziv-aflibercept is a fusion protein which acts as a decoy receptor for vascular endothelial growth factor (VEGF-A, VEGF-B, and placental growth factor (PlGF; it was approved in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI for the treatment of patients with metastatic colorectal cancer that is resistant to or has progressed after an oxaliplatin-containing fluoropyrimidine-based regimen. Herein we review the role of tumor angiogenesis as the rationale for antiangiogenic therapy, the clinical data associated with ziv-aflibercept, and its current role as a treatment option compared to other antiangiogenic agents, such as bevacizumab and regorafenib. Keywords: aflibercept, angiogenesis, colorectal cancer

  18. Clinical Outcomes of Colorectal Cancer in Kenya

    African Journals Online (AJOL)

    Cancer in Kenya tients with sufficient information on CRC pathology, treatment and follow up were included. Patient profile, tumor sub-site, pathology details, recurrence and mor- tality data were ... Introduction. The incidence of colorectal cancer (CRC) in the devel- .... included the presence of co-morbidity, recurrence, cura-.

  19. Colorectal Cancer: What You Should Know

    Science.gov (United States)

    ... Maintain a healthy weight Limit the amount of alcohol you drink Don’t smoke and avoid second-hand smoke For more information For more information about treatments for colorectal cancer, call 1-800-4-CANCER. Updated: ... Products Tobacco Products Vaccines, Blood & Biologics Articulos en Espanol Alimentos y Bebidas Cosméticos Dispositivos ...

  20. Colorectal cancer screening | Schneider | Continuing Medical ...

    African Journals Online (AJOL)

    Colorectal cancer (CRC) is one of the most common cancers in the Western world, with an estimated incidence of 148 810 cases in the USA in 2008, and about 50 000 deaths from this disease. If detected early, patients with disease localised to the colonic wall have a 5-year survival of 90%. The 5-year survival for patients ...

  1. Colorectal Cancer Screening: A Guide to the Guidelines

    Directory of Open Access Journals (Sweden)

    Douglas K Rex

    1999-01-01

    Full Text Available The two most recent guidelines for colorectal cancer screening are those of the Agency for Healthcare Policy and Research, and the American Cancer Society. The guidelines are similar in many regards and reflect current literature, consensus opinion and compromise between members of multidisciplinary panels. The emphasis of both guidelines is to increase the options available for colorectal cancer screening. Increasing choice should expand the attractiveness of colorectal cancer screening to more patients and physicians, and the development of guidelines should help compel payers to provide reimbursement for colorectal cancer screening. These guidelines are summarized and evaluated as they pertain to colorectal cancer screening.

  2. YAP transcriptionally regulates COX-2 expression and GCCSysm-4 (G-4), a dual YAP/COX-2 inhibitor, overcomes drug resistance in colorectal cancer.

    Science.gov (United States)

    Li, Wei; Cao, Yuanyuan; Xu, Jinling; Wang, Ying; Li, Weijie; Wang, Qian; Hu, Ziwei; Hao, Yaping; Hu, Li; Sun, Yawen; Xu, Guanglin; Ao, Guizhen

    2017-10-16

    Chemotherapy resistance remains a major challenge in cancer treatment. COX-2 (cyclooxygenase 2) is involved in drug resistance and poor prognosis of many neoplastic diseases or cancers. However, investigations identifying new modulators of COX-2 pathway and searching for new chemicals targeting these valid resistant biomarkers are still greatly needed. HCT15, HCT-116, HT-29, COLO205, FHC, IMCE, SW480 cell lines were used to detect the expression of YAP and COX-2. Site-directed mutagenesis, luciferase reporter analysis and ChIP assay were used to test whether YAP activated COX-2 transcription through interaction with TEAD binding sites in the promoter of COX-2. Cell line models exhibiting overexpression or knockdown of some genes were generated using transfection agents. Coimmunoprecipitation was used to detect protein mutual interaction. mRNA and protein levels were measured by qRT-PCR and western blot respectively. Here, we reported that both YAP and COX-2 were overexpressed in colorectal cancer cells. YAP increased COX-2 expression at the level of transcription requiring intact TEAD binding sites in the COX-2 promoter. YAP conferred drug resistance through COX-2 and its related effectors such as MCL, MDR, Survivin. GCCSysm-4 (G-4), a YAP and COX-2 inhibitor, effectively inhibited both YAP and COX-2 activation, induced apoptosis and decreased viability in Taxol-resistant cells. Inhibition of YAP and COX-2 acted synergistically and more efficiently reduced the resistance of CRC cells than either of them alone. Our data provide new mechanisms that YAP is a new upstream regulator of COX-2 pathway and plays an important role in conferring resistance in CRC cells. G-4, targeting YAP-COX-2, may be a novel valuable strategy to combat resistance in CRC.

  3. Curcumin Suppresses the Colon Cancer Proliferation by Inhibiting Wnt/β-Catenin Pathways via miR-130a

    Directory of Open Access Journals (Sweden)

    Huiqiang Dou

    2017-11-01

    Full Text Available Curcumin exhibits anti-tumor effects in several cancers, including colorectal carcinoma (CRC, but the detailed mechanisms are still unclear. Here we studied the mechanisms underlying the anti-tumor effect of curcumin in colon cancer cells. SW480 cells were injected into mice to establish the xenograft tumor model, followed by evaluation of survival rate with the treatment of curcumin. The expression levels of β-catenin, Axin and TCF4 were measured in the SW480 cells in the absence or presence of curcumin. Moreover, miRNAs related to the curcumin treatment were also detected in vitro. Curcumin could suppress the growth of colon cancer cells in the mouse model. This anti-tumor activity of curcumin was exerted by inhibiting cell proliferation rather than promoting cell apoptosis. Further study suggested that curcumin inhibited cell proliferation by suppressing the Wnt/β-catenin pathway. MiR-130a was down-regulated by curcumin treatment, and overexpressing miR-130a could abolish the anti-tumor activity of curcumin. Our study confirms that curcumin is able to inhibit colon cancer by suppressing the Wnt/β-catenin pathways via miR-130a. MiR-130a may serve as a new target of curcumin for CRC treatment.

  4. Colorectal cancer stages transcriptome analysis.

    Directory of Open Access Journals (Sweden)

    Tianyao Huo

    Full Text Available Colorectal cancer (CRC is the third most common cancer and the second leading cause of cancer-related deaths in the United States. The purpose of this study was to evaluate the gene expression differences in different stages of CRC. Gene expression data on 433 CRC patient samples were obtained from The Cancer Genome Atlas (TCGA. Gene expression differences were evaluated across CRC stages using linear regression. Genes with p≤0.001 in expression differences were evaluated further in principal component analysis and genes with p≤0.0001 were evaluated further in gene set enrichment analysis. A total of 377 patients with gene expression data in 20,532 genes were included in the final analysis. The numbers of patients in stage I through IV were 59, 147, 116 and 55, respectively. NEK4 gene, which encodes for NIMA related kinase 4, was differentially expressed across the four stages of CRC. The stage I patients had the highest expression of NEK4 genes, while the stage IV patients had the lowest expressions (p = 9*10-6. Ten other genes (RNF34, HIST3H2BB, NUDT6, LRCh4, GLB1L, HIST2H4A, TMEM79, AMIGO2, C20orf135 and SPSB3 had p value of 0.0001 in the differential expression analysis. Principal component analysis indicated that the patients from the 4 clinical stages do not appear to have distinct gene expression pattern. Network-based and pathway-based gene set enrichment analyses showed that these 11 genes map to multiple pathways such as meiotic synapsis and packaging of telomere ends, etc. Ten of these 11 genes were linked to Gene Ontology terms such as nucleosome, DNA packaging complex and protein-DNA interactions. The protein complex-based gene set analysis showed that four genes were involved in H2AX complex II. This study identified a small number of genes that might be associated with clinical stages of CRC. Our analysis was not able to find a molecular basis for the current clinical staging for CRC based on the gene expression patterns.

  5. Colorectal Cancer Metastasis to the Thymus Gland: Rare Presentation of Colorectal Cancer as Anterior Mediastinal Mass

    Directory of Open Access Journals (Sweden)

    H. Charles Peters

    2017-01-01

    Full Text Available Despite improved screening modalities, 15–25% of newly diagnosed colorectal cancers are metastatic at the time of diagnosis. The vast majority of these cases present as hepatic metastasis; however, 22% present with concomitant extrahepatic disease. The thymus gland is an uncommon site of metastasis for any primary malignancy, particularly, colorectal cancer given its vascular and lymphatic drainage. This case report details our experience with a rare case of colorectal cancer metastasis to the thymus gland presenting as a symptomatic mediastinal mass.

  6. Molecular alterations and biomarkers in colorectal cancer

    Science.gov (United States)

    Grady, William M.; Pritchard, Colin C.

    2013-01-01

    The promise of precision medicine is now a clinical reality. Advances in our understanding of the molecular genetics of colorectal cancer genetics is leading to the development of a variety of biomarkers that are being used as early detection markers, prognostic markers, and markers for predicting treatment responses. This is no more evident than in the recent advances in testing colorectal cancers for specific molecular alterations in order to guide treatment with the monoclonal antibody therapies cetuximab and panitumumab, which target the epidermal growth factor receptor (EGFR). In this review, we update a prior review published in 2010 and describe our current understanding of the molecular pathogenesis of colorectal cancer and how these alterations relate to emerging biomarkers for early detection and risk stratification (diagnostic markers), prognosis (prognostic markers), and the prediction of treatment responses (predictive markers). PMID:24178577

  7. [Molecular biology in the development of colorectal cancer].

    Science.gov (United States)

    Nagawa, H; Muto, T

    1999-12-01

    In 1988, Vogelstein and colleagues published a paper entitled "Genetic alterations during colorectal-tumor development." This marked the beginning of a series of advances in our understanding of how colorectal cancer develops. This paper also provided evidence for the adenoma-carcinoma sequence. Furthermore, the importance of DNA mismatch repair genes in hereditary nonpolyposis colorectal cancer has been recognized. We herein discuss the development of colorectal cancer on the basis of molecular biology, including specific abnormalities of related genes.

  8. Anticancer activity of calyx of Diospyros kaki Thunb. through downregulation of cyclin D1 via inducing proteasomal degradation and transcriptional inhibition in human colorectal cancer cells.

    Science.gov (United States)

    Park, Su Bin; Park, Gwang Hun; Song, Hun Min; Son, Ho-Jun; Um, Yurry; Kim, Hyun-Seok; Jeong, Jin Boo

    2017-09-05

    Although it has been reported to contain high polyphenols, the pharmacological studies of the calyx of Diospyros kaki Thunb (DKC) have not been elucidated in detail. In this study, we elucidated anti-cancer activity and potential molecular mechanism of DKC against human colorectal cancer cells. Anti-cell proliferative effect of 70% ethanol extracts from the calyx of Diospyros kaki (DKC-E70) was evaluated by MTT assay. The effect of DKC-E70 on the expression of cyclin D1 in the protein and mRNA level was evaluated by Western blot and RT-PCR, respectively. DKC-E70 suppressed the proliferation of human colorectal cancer cell lines such as HCT116, SW480, LoVo and HT-29. Although DKC-E70 decreased cyclin D1 expression in protein and mRNA level, decreased level of cyclin D1 protein by DKC-E70 occurred at the earlier time than that of cyclin D1 mRNA, which indicates that DKC-E70-mediated downregulation of cyclin D1 protein may be a consequence of the induction of degradation and transcriptional inhibition of cyclin D1. In cyclin D1 degradation, we found that cyclin D1 downregulation by DKC-E70 was attenuated in presence of MG132. In addition, DKC-E70 phosphorylated threonine-286 (T286) of cyclin D1 and T286A abolished cyclin D1 downregulation by DKC-E70. We also observed that DKC-E70-mediated T286 phosphorylation and subsequent cyclin D1 degradation was blocked in presence of the inhibitors of ERK1/2, p38 or GSK3β. In cyclin D1 transcriptional inhibition, DKC-E70 inhibited the expression of β-catenin and TCF4, and β-catenin/TCF-dependent luciferase activity. Our results suggest that DKC-E70 may downregulate cyclin D1 as one of the potential anti-cancer targets through cyclin D1 degradation by T286 phosphorylation dependent on ERK1/2, p38 or GSK3β, and cyclin D1 transcriptional inhibition through Wnt signaling. From these findings, DKC-E70 has potential to be a candidate for the development of chemoprevention or therapeutic agents for human colorectal cancer.

  9. Microsatellite Instability Markers Status in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Giti Esmailnia

    2014-12-01

    Full Text Available Background: Colorectal cancer (CRC is the third most prevalent and the third leading cause of cancer-related deaths in Iran. Our aim was to investigate five mononucleotide statuses among Iranian patients with sporadic colorectal cancer. Materials and Methods: In this experimental study 80 sporadic CRC patients were evaluated for microsatellite instability (MSI. The pentaplex panel including 5 quasi mononucleotide microsatellite markers (NR-21, BAT-26, BAT-25, NR-27 and NR-24 was used. The MSI analysis was performed on paired tumoral DNA from cancerous tissues and genomic DNA from whole blood. MSI carriers were identified by analysis of tumor tissue using polymerase chain reaction. Results: Our findings showed that microsatellite instability was detected in 36 of 80 cases (45% with colorectal cancer. MSI analysis revealed that 17 cases of MSI-H (21%, 19 MSI-L (23% and 44 microsatellite stable tumors (55%. Instability is observed in the tumoral DNA compared to the DNA from the normal DNA sample. The most instable markers were NR-21, NR-24 in which instability was detected in 45% of patients. Conclusion: Using a panel including 3 mentioned MSI markers should be more promising markers for identifying MSI status in patients with sporadic colorectal cancer.

  10. Molecular Dissection of Microsatellite Instable Colorectal Cancer

    Science.gov (United States)

    Vilar, Eduardo; Tabernero, Josep

    2013-01-01

    Colorectal cancer was one of the first solid tumors to be classified based on molecular profiling. Microsatellite instability has allowed researchers to distinguish a specific subtype of colorectal cancer that has a clearly identified molecular origin (mismatch repair deficiency), arises on a hereditary and sporadic basis, is linked to a clear clinicopathological profile and has prognostic implications. Inconclusive predictive data along with a paucity of targeted drug development have prevented this molecular classification system from being implemented in the clinical setting. New high-throughput genomic data have validated it, thus stressing the fact that it is ready to be applied clinically. PMID:23454900

  11. Adherence to Colorectal Cancer Screening

    Science.gov (United States)

    Inadomi, John M.; Vijan, Sandeep; Janz, Nancy K.; Fagerlin, Angela; Thomas, Jennifer P.; Lin, Yunghui V.; Muñoz, Roxana; Lau, Chim; Somsouk, Ma; El-Nachef, Najwa; Hayward, Rodney A.

    2012-01-01

    Background Despite evidence that several colorectal cancer (CRC) screening strategies can reduce CRC mortality, screening rates remain low. This study aimed to determine whether the approach by which screening is recommended influences adherence. Methods We used a cluster randomization design with clinic time block as the unit of randomization. Persons at average risk for development of CRC in a racially/ethnically diverse urban setting were randomized to receive recommendation for screening by fecal occult blood testing (FOBT), colonoscopy, or their choice of FOBT or colonoscopy. The primary outcome was completion of CRC screening within 12 months after enrollment, defined as performance of colonoscopy, or 3 FOBT cards plus colonoscopy for any positive FOBT result. Secondary analyses evaluated sociodemographic factors associated with completion of screening. Results A total of 997 participants were enrolled; 58% completed the CRC screening strategy they were assigned or chose. However, participants who were recommended colonoscopy completed screening at a significantly lower rate (38%) than participants who were recommended FOBT (67%) (PChinese) completed screening more often than African Americans. Moreover, non-white participants adhered more often to FOBT, while white participants adhered more often to colonoscopy. Conclusions The common practice of universally recommending colonoscopy may reduce adherence to CRC screening, especially among racial/ethnic minorities. Significant variation in overall and strategy-specific adherence exists between racial/ethnic groups; however, this may be a proxy for health beliefs and/or language. These results suggest that patient preferences should be considered when making CRC screening recommendations. Trial Registration clinicals.gov Identifier: NCT00705731 PMID:22493463

  12. An audit of colorectal cancer histopathology reports in a Tertiary ...

    African Journals Online (AJOL)

    Objective: To audit the completeness of histopathologic reports of Colorectal Cancer for prognostic information in a tertiary care hospital in the light of the minimum reporting standards for colorectal cancer resections recently proposed for use in Nigeria. Material and Methods: Twenty–five histopathology reports of colorectal ...

  13. Liver-directed therapies in colorectal cancer.

    Science.gov (United States)

    Alsina, Janivette; Choti, Michael A

    2011-08-01

    Colorectal cancer is the third leading cause of cancer-related deaths in the United States. Historically, the majority of patients that presented with metastatic disease to the liver were treated with systemic chemotherapy only but advances in imaging, surgical techniques, and non-resectional approaches have expanded the indications for liver-directed interventions. Current approaches used in patients with liver-only or liver-dominant metastatic disease include surgical resection, direct tumor ablation strategies, the use of intra-arterial infusions, and radiation therapies. The use of these liver-directed therapies in selected patients with colorectal liver metastases has led to significant improvements in overall survival. We review the clinical data and progress using liver-directed therapies in the treatment of colorectal liver metastases. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. An Enterovirus-Like RNA Construct for Colon Cancer Suicide Gene Therapy.

    Science.gov (United States)

    Rasekhian, Mahsa; Teimoori-Toolabi, Ladan; Amini, Safieh; Azadmanesh, Kayhan

    2015-01-01

    In gene therapy, the use of RNA molecules as therapeutic agents has shown advantages over plasmid DNA, including higher levels of safety. However, transient nature of RNA has been a major obstacle in application of RNA in gene therapy. Here, we used the internal ribosomal entry site of encephalomyocarditis virus and the 3' non-translated region of Poliovirus to design an enterovirus-like RNA for the expression of a reporter gene (enhanced green fluorescent protein) and a suicide gene (thymidine kinase of herpes simplex virus). The expression of these genes was evaluated by flow cytometry and cytotoxicity assay in human colorectal adenocarcinoma cell line (SW480). We then armed RNA molecules with a target sequence for hsa-miR-143 to regulate their expression by microRNA (miRNA) mimics. The results showed effective expression of both genes by Entrovirus-like RNA constructs. The data also showed that the restoration of hsa-miR-143 expression in SW480 leads to a significant translation repression of the introduced reporter and suicide genes. Collectively, our data suggest the potential use of Entrovirus-like RNA molecules in suicide gene therapy. Additionally, as a consequence of the possible downregulated miRNA expression in cancerous tissues, a decreased expression of gene therapy constructs armed with target sequences for such miRNA in cancer tissue is expected.

  15. Hereditary colorectal cancer syndromes and genetic testing.

    Science.gov (United States)

    Macaron, Carole; Leach, Brandie H; Burke, Carol A

    2015-01-01

    Colorectal cancer (CRC) is a leading cause of cancer and cancer deaths in the Western world. Approximately 5-10% of CRC are hereditary, due to a defined genetic cause. Individuals and families affected with a hereditary CRC syndrome exhibit benign and malignant extra-intestinal tumors, require aggressive cancer screening and benefit from management by a multi-disciplinary team of professionals. The clinical manifestations, genetic causes and current management of patients with hereditary colon cancer syndrome is provided. © 2014 Wiley Periodicals, Inc.

  16. Hereditary & familial colorectal cancer : Identification, characteristics, surveillance

    NARCIS (Netherlands)

    Kallenberg, F.G.J.

    2017-01-01

    Of all colorectal cancer (CRC) cases, 15-20% is related to familial or hereditary factors. Diagnosing familial and hereditary CRC syndromes is important for several reasons. One of these is that surveillance colonoscopies can reduce CRC incidence and mortality importantly. A complete family history

  17. Diagnostic interval and mortality in colorectal cancer

    DEFF Research Database (Denmark)

    Tørring, Marie Louise; Frydenberg, Morten; Hamilton, William

    2012-01-01

    Objective To test the theory of a U-shaped association between time from the first presentation of symptoms in primary care to the diagnosis (the diagnostic interval) and mortality after diagnosis of colorectal cancer (CRC). Study Design and Setting Three population-based studies in Denmark...

  18. Why I Got Tested for Colorectal Cancer

    Centers for Disease Control (CDC) Podcasts

    2016-02-29

    CDC’s Dr. Lisa Richardson explains why she got tested for colorectal cancer when she turned 50 years old. .  Created: 2/29/2016 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 2/29/2016.

  19. Indeterminate Pulmonary Nodules in Colorectal-Cancer

    DEFF Research Database (Denmark)

    Nordholm-Carstensen, Andreas; Jorgensen, Lars N; Wille-Jørgensen, Peer A

    2015-01-01

    BACKGROUND: The clinical significance of indeterminate pulmonary nodules (IPN) at staging computed tomography (CT) for colorectal cancer (CRC), and the optimal diagnostic approach, are debated. This study aimed to analyse variability in radiologists' detection of IPN at staging CT for CRC. METHOD...

  20. Inflammatory bowel disease and colorectal cancer

    Directory of Open Access Journals (Sweden)

    Andreja Ocepek

    2006-12-01

    Full Text Available Background: Colorectal cancer is one of the most frequent cancers in developed countries and Slovenia, and the incidence is still rising. Groups of people with higher risk for colorectal cancer are well defined. Among them are patients with inflammatory bowel disease. The risk is highest in patients in whom whole large bowel is affected by inflammation, it rises after 8 to 10 years and increases with the duration of the disease. Precancerous lesion is a displastic, chronically inflammed mucosa and not an adenoma as in cases of sporadic colorectal carcinoma.Conclusions: Many studies suggest that the influence of genetic factors differs between sporadic and inflammatory bowel disease related colorectal cancer. Symptomatic patients at the time of diagnosis have a much worse prognosis. The goal of prevention programes is therefore discovering early precancerous lesions. Established screening protocols are based on relatively frequent colonoscopies which are inconvinient for the patient as well as the endoscopist. Use of specific genetic markers, mutations of candidate genes, as a screening method and a prognostic predictor could greatly lighten therapeutic decisions.

  1. Population-based screening for colorectal cancer

    NARCIS (Netherlands)

    L. Hol (Lieke)

    2010-01-01

    textabstractThe incidence of colorectal cancer (CRC) shows considerable geographical differences around the world. The highest incidence rates are mainly seen in the Western world including North America, Australia/New Zealand, Western Europe, and Japan. Development countries report the lowest

  2. Hereditary Colorectal Cancer (CRC Program in Latvia

    Directory of Open Access Journals (Sweden)

    Irmejs Arvids

    2003-12-01

    Full Text Available Abstract Introduction The aim of the study is to evaluate the incidence and phenotype - genotype characteristics of hereditary colorectal cancer syndromes in Latvia in order to develop the basis of clinical management for patients and their relatives affected by these syndromes. Materials and methods From 02/1999-09/2002 in several hospitals in Latvia cancer family histories were collected from 865 patients with CRC. In families suspected of having a history consistent with a hereditary colorectal cancer syndrome, DNA testing for MLH1, MSH2 and MSH6 genes was performed. In addition immunohistochemical (IH examination of the normal and cancer tissue from large bowel tumors for MSH2 and MSH6 protein expression was performed prior to DNA analysis. Results From the 865 CRC cases only 3 (0.35% pedigrees fulfilled the Amsterdam II criteria of Hereditary Nonpolyposis Colorectal Cancer (HNPCC and 15 cases (1.73% were suspected of HNPCC. In 69 cases (8% with a cancer family aggregation (CFA were identified. Thus far 27 IH analyses have been performed and in 3 cancers homogenous lack of MSH2 or MSH6 protein expression was found. In one of these cases a mutation in MSH6 was identified. In 18 patients suspected of HNPCC or of matching the Amsterdam II criteria, denaturing high performance liquid chromatography (DHPLC followed by DNA sequencing of any heteroduplexes of the 35 exons comprising both MLH1 and MSH2 was performed revealing 3 mutations. For all of kindreds diagnosed definitively or with a high probability of being an HNPCC family appropriate recommendations concerning prophylactic measures, surveillance and treatment were provided in written form. Conclusions Existing pedigree/clinical data suggest that in Latvia the frequency of HNPCC is around 2% of consecutive colorectal cancer patients. It is crucial that genetic counseling is an integral part of cancer family syndrome management.

  3. Nutrients Impact the Pathogenesis and Development of Colorectal Cancer.

    Science.gov (United States)

    Du, Wan; Fang, Jing-Yuan

    2016-05-01

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

  4. Diet, aberrant crypt foci and colorectal cancer.

    Science.gov (United States)

    Bruce, W R; Archer, M C; Corpet, D E; Medline, A; Minkin, S; Stamp, D; Yin, Y; Zhang, X M

    1993-11-01

    We have used the aberrant crypt focus (ACF) assay to test and develop hypotheses linking diet and colon cancer. The hypotheses were suggested by epidemiological studies that identified possible dietary factors associated with colorectal cancer risk. The ACF assay was used to quantitate the effect of the dietary factors on the initiation and growth of these putative precursors of colon cancers in experimental animals. Using this approach we have developed 3 new hypotheses for the role of diet in colorectal cancer. These are (1) a risk associated with 5-hydroxymethyl-2-furaldehyde in caramelized sugar, (2) a risk associated with some factor in thermolyzed casein, and (3) a risk associated with single nutrient boluses of sucrose and fructose. The importance of these hypotheses has still to be tested in long term carcinogenesis experiments, in analytic epidemiology studies and then, perhaps, in intervention trials.

  5. Nutrition and colorectal cancer risk: a literature review.

    Science.gov (United States)

    Doyle, Veronica Castillo

    2007-01-01

    Though no one knows why one person gets cancer and another does not, there are ways to decrease the chances of getting cancer. In the case of colorectal cancers, diet may be a preventative factor. The objective of this literature review was to determine whether a person's nutritional diet has an effect on his or her risk of getting colorectal cancer. Studies done by a number of researchers on the correlation between colorectal cancer risk and diet were reviewed. Research papers investigating dietary patterns and colorectal cancer incidence were examined. A synthesis of this literature suggests a diet high in red meat and fat may increase a person's risk of getting colorectal cancer. Contrary to previous recommendations, there is no strong evidence to suggest that fiber intake (including more fruits and vegetables) has any effect on colorectal cancer risk.

  6. Access to Cancer Services for Rural Colorectal Cancer Patients

    Science.gov (United States)

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

    2008-01-01

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

  7. Screening for Colorectal Cancer – Quality Colonoscopy and Other ...

    African Journals Online (AJOL)

    The “pink” breast cancer awareness initiative is in our face in South Africa, but we must be mindful of the world-wide cancer awareness programme of all forms of cancer. Gastroenterological and Colorectal bodies abroad were prominent in promoting March as Colorectal Cancer awareness month ...

  8. Folate-related nutrients, genetic polymorphisms, and colorectal cancer risk: the fukuoka colorectal cancer study.

    Science.gov (United States)

    Morita, Makiko; Yin, Guang; Yoshimitsu, Shin-ichiro; Ohnaka, Keizo; Toyomura, Kengo; Kono, Suminori; Ueki, Takashi; Tanaka, Masao; Kakeji, Yoshihiro; Maehara, Yoshihiko; Okamura, Takeshi; Ikejiri, Koji; Futami, Kitaroh; Maekawa, Takafumi; Yasunami, Yohichi; Takenaka, Kenji; Ichimiya, Hitoshi; Terasaka, Reiji

    2013-01-01

    One-carbon metabolism plays an important role in colorectal carcinogenesis. Meta-analyses have suggested protective associations of folate and vitamin B6 intakes with colorectal cancer primarily based on studies in Caucasians, and genetic polymorphisms pertaining to the folate metabolism have been a matter of interest. Less investigated are the roles of methionine synthase (MTR) and thymidylate synthetase (TS) polymorphisms in colorectal carcinogenesis. In a study of 816 cases and 815 community controls in Japan, we investigated associations of dietary intakes of folate, methionine, vitamin B2, vitamin B6, and vitamin B12 with colorectal cancer risk. The associations with MTR 2756A>G, MTRR 66A>G, and TSER repeat polymorphism were examined in 685 cases and 778 controls. Methionine and vitamin B12 intakes were inversely associated with colorectal cancer risk, but the associations were totally confounded by dietary calcium and n-3 fatty acids. The other nutrients showed no association with the risk even without adjustment for calcium and n-3 fatty acids. The TSER 2R allele was dose-dependently associated with an increased risk. The MTR and MTRR polymorphisms were unrelated to colorectal cancer risk. There was no measurable gene-gene or gene-nutrient interaction, but increased risk associated with the TSER 2R allele seemed to be confined to individuals with high folate status. This study does not support protective associations for folate and vitamin B6. The TSER 2R allele may confer an increased risk of colorectal cancer. The role of the TSER polymorphism in colorectal carcinogenesis may differ by ethnicity.

  9. Down-regulation of liver-intestine cadherin enhances noscapine-induced apoptosis in human colon cancer cells.

    Science.gov (United States)

    Tian, Xia; Liu, Meng; Zhu, Qingxi; Tan, Jie; Liu, Weijie; Wang, Yanfen; Chen, Wei; Zou, Yanli; Cai, Yishan; Han, Zheng; Huang, Xiaodong

    2017-09-01

    The aim of the present study was to explore the signaling pathway of noscapine which induces apoptosis by blocking liver-intestine cadherin (CDH17) gene in colon cancer SW480 cells. Human colon cancer SW480 cells were transfected with CDH17 interference vector and treatment with 10 µmol/L noscapine. The proliferation and apoptosis of SW480 cells were detected by MTT assay and AnnexinV-FITC/PI flow cytometry kit (BD), respectively. Cell invasion were assessed by transwell assays. Apoptosis related proteins (Cyt-c, Bax, Bcl-2 and Bcl-xL) levels were evaluated by western blot. Compared to the noscapine group, the proliferation was decreased significantly and the apoptosis was increased significantly in SW480 cells of the siCDH17+noscapine group. Cyt-c and Bax protein levels in siCDH17+noscapine group was higher than that of the noscapine group, but Bcl-2 and Bcl-xL protein levels in siCDH17+noscapine group were lower than that of the noscapine group. Moreover, up-expression of CDH17 inhibited the efficacy of noscapine-induced apoptosis in SW480 cells. We inferred that down-expression of extrinsic CDH17 gene can conspicuously promote apoptosis-inducing effects of noscapine on human colon cancer SW480 cells, which is a novel strategy to improve chemotherapeutic effects on colon cancer.

  10. Prevalence of hereditary nonpolyposis colorectal cancer in patients with colorectal cancer in Iran: a systematic review

    Directory of Open Access Journals (Sweden)

    Abbas Esmaeilzadeh

    2016-07-01

    Full Text Available Introduction: Colorectal cancer (CRC is the third leading cause of cancer deaths in the world, and hereditary factors and family history are responsible for the incidence and development of the disease in 20 to 30% of cases. Lynch syndrome, or hereditary nonpolyposis colorectal cancer (HNPCC, is the most common hereditary form of CRC that is inherited in an autosomal dominant manner. This study consisted of a systematic literature review of research articles that described the prevalence of HNPCC in Iranian patients with CRC. Methods: A systematic literature search was conducted in the PubMed, Scopus, IranMedex, and Google Scholar databases to identify relevant articles that describe HNPCC or Lynch syndrome in patients with CRC in Iran. For this purpose, a keyword search of the following terms was employed: (((Hereditary nonpolyposis colorectal cancer OR HNPCC OR Lynch syndrome AND (colorectal cancer OR familial colorectal cancer OR colon cancer OR rectal cancer OR bowel cancer AND IRAN. All eligible documents were collected, and the desired data were qualitatively analyzed.Result: Of the 67 articles that were found via the initial database search, only 12 were deemed to be of relevance to the current study. These articles included a total population of 3237 and this sample was selected and qualitatively analyzed. The findings of the review revealed that the frequency of mutation in MLH1, MSH2, PMS2, and MSH6 genes varied between 23.1% and 62.5% among the studied families. This indicated that HNPCC is linked with up to 5.5% of the total cases of colorectal cancers in Iran.Conclusion: The results of this study revealed that the hereditary form of HNPCC or Lynch syndrome is significantly high among patients with CRC in Iran

  11. Colorectal Cancer Stem Cells and Cell Death

    Energy Technology Data Exchange (ETDEWEB)

    Catalano, Veronica [Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy); Gaggianesi, Miriam [Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy); Department of Cellular and Molecular Oncology, IRCCS Fondazione Salvatore Maugeri, Via Salvatore Maugeri, 27100 Pavia, PV (Italy); Spina, Valentina; Iovino, Flora [Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy); Dieli, Francesco [Departement of Biopathology and Medicine Biotechnologies, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy); Stassi, Giorgio, E-mail: giorgio.stassi@unipa.it [Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy); Department of Cellular and Molecular Oncology, IRCCS Fondazione Salvatore Maugeri, Via Salvatore Maugeri, 27100 Pavia, PV (Italy); Todaro, Matilde [Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy)

    2011-04-11

    Nowadays it is reported that, similarly to other solid tumors, colorectal cancer is sustained by a rare subset of cancer stem–like cells (CSCs), which survive conventional anticancer treatments, thanks to efficient mechanisms allowing escape from apoptosis, triggering tumor recurrence. To improve patient outcomes, conventional anticancer therapies have to be replaced with specific approaches targeting CSCs. In this review we provide strong support that BMP4 is an innovative therapeutic approach to prevent colon cancer growth increasing differentiation markers expression and apoptosis. Recent data suggest that in colorectal CSCs, protection from apoptosis is achieved by interleukin-4 (IL-4) autocrine production through upregulation of antiapoptotic mediators, including survivin. Consequently, IL-4 neutralization could deregulate survivin expression and localization inducing chemosensitivity of the colon CSCs pool.

  12. Microsatellite Instability of Gastric and Colorectal Cancers as a Predictor of Synchronous Gastric or Colorectal Neoplasms.

    Science.gov (United States)

    Kim, Young Beak; Lee, Sun-Young; Kim, Jeong Hwan; Sung, In-Kyung; Park, Hyung Seok; Shim, Chan Sup; Han, Hye Seung

    2016-03-01

    Microsatellite instability (MSI) plays a crucial role in gastrointestinal carcinogenesis. The aim of this study was to clarify whether MSI is a useful marker for predicting synchronous gastric and colorectal neoplasms. Consecutive patients who underwent both esophagogastroduodenoscopy and colonoscopy before the resection of gastric or colorectal cancers were included. MSI was analyzed using two mononucleotide and three dinucleotide markers. In total, 434 gastric cancers (372 microsatellite stability [MSS], 21 low incidence of MSI [MSI-L], and 41 high incidence of MSI [MSI-H]) and 162 colorectal cancers (138 MSS, 9 MSI-L, and 15 MSI-H) were included. Patients with MSI gastric cancer had a higher prevalence of synchronous colorectal cancer, colorectal adenoma, and gastric adenoma than those with MSS gastric cancers (4.8% vs 0.5%, p=0.023; 11.3% vs 3.2%, p=0.011; 3.2% vs 1.2%, p=0.00, respectively). The prevalence of synchronous colorectal adenomas was highest in MSI-L gastric cancers (19.0%), compared with MSI-H (7.3%) or MSS (3.2%) gastric cancers (p=0.002). In addition, there were no significant differences in the prevalence rates of synchronous colorectal adenoma among the MSI-H (13.3%), MSI-L (11.1%), and MSS (12.3%) colorectal cancers (p=0.987). The presence of MSI in gastric cancer may be a predictor of synchronous gastric and colorectal neoplasms, whereas MSI in colorectal cancer is not a predictor of synchronous colorectal adenoma.

  13. Microsatellite Instability of Gastric and Colorectal Cancers as a Predictor of Synchronous Gastric or Colorectal Neoplasms

    Science.gov (United States)

    Kim, Young Beak; Lee, Sun-Young; Kim, Jeong Hwan; Sung, In-Kyung; Park, Hyung Seok; Shim, Chan Sup; Han, Hye Seung

    2016-01-01

    Background/Aims Microsatellite instability (MSI) plays a crucial role in gastrointestinal carcinogenesis. The aim of this study was to clarify whether MSI is a useful marker for predicting synchronous gastric and colorectal neoplasms. Methods Consecutive patients who underwent both esophagogastroduodenoscopy and colonoscopy before the resection of gastric or colorectal cancers were included. MSI was analyzed using two mononucleotide and three dinucleotide markers. Results In total, 434 gastric cancers (372 microsatellite stability [MSS], 21 low incidence of MSI [MSI-L], and 41 high incidence of MSI [MSI-H]) and 162 colorectal cancers (138 MSS, 9 MSI-L, and 15 MSI-H) were included. Patients with MSI gastric cancer had a higher prevalence of synchronous colorectal cancer, colorectal adenoma, and gastric adenoma than those with MSS gastric cancers (4.8% vs 0.5%, p=0.023; 11.3% vs 3.2%, p=0.011; 3.2% vs 1.2%, p=0.00, respectively). The prevalence of synchronous colorectal adenomas was highest in MSI-L gastric cancers (19.0%), compared with MSI-H (7.3%) or MSS (3.2%) gastric cancers (p=0.002). In addition, there were no significant differences in the prevalence rates of synchronous colorectal adenoma among the MSI-H (13.3%), MSI-L (11.1%), and MSS (12.3%) colorectal cancers (p=0.987). Conclusions The presence of MSI in gastric cancer may be a predictor of synchronous gastric and colorectal neoplasms, whereas MSI in colorectal cancer is not a predictor of synchronous colorectal adenoma. PMID:26087787

  14. Exercise barriers in Korean colorectal cancer patients.

    Science.gov (United States)

    Kang, Dong-Woo; Chung, Jae Youn; Lee, Mi Kyung; Lee, Junga; Park, Ji-Hye; Kim, Dong-Il; Jones, Lee W; Ahn, Joong Bae; Kim, Nam Kyu; Jeon, Justin Y

    2014-01-01

    To identify barriers to exercise in Korean colorectal cancer patients and survivors, and to analyze differences in exercise barriers by age, gender, treatment status, and physical activity level. A total of 427 colorectal cancer patients and survivors from different stages and medical status completed a self-administered questionnaire that surveyed their barriers to exercise and exercise participation. The greatest perceived exercise barriers for the sampled population as a whole were fatigue, low level of physical fitness, and poor health. Those under 60-years old reported lack of time (p=0.008), whereas those over 60 reported low level of physical fitness (p=0.014) as greater exercise barriers than their counterparts. Women reported fatigue as a greater barrier than men (pACSM guidelines, cancer-related exercise barriers were additionally reported (p<0.001), compared to those who were. Our study suggests that fatigue, low level of physical fitness, and poor health are most reported exercise barriers for Korean colorectal cancer survivors and there are differences in exercise barriers by age, sex, treatment status, and physical activity level. Therefore, support for cancer patients should be provided considering these variables to increase exercise participation.

  15. A transcriptome anatomy of human colorectal cancers

    Directory of Open Access Journals (Sweden)

    Zhang Hao

    2006-02-01

    Full Text Available Abstract Background Accumulating databases in human genome research have enabled integrated genome-wide study on complicated diseases such as cancers. A practical approach is to mine a global transcriptome profile of disease from public database. New concepts of these diseases might emerge by landscaping this profile. Methods In this study, we clustered human colorectal normal mucosa (N, inflammatory bowel disease (IBD, adenoma (A and cancer (T related expression sequence tags (EST into UniGenes via an in-house GetUni software package and analyzed the transcriptome overview of these libraries by GOTree Machine (GOTM. Additionally, we downloaded UniGene based cDNA libraries of colon and analyzed them by Xprofiler to cross validate the efficiency of GetUni. Semi-quantitative RT-PCR was used to validate the expression of β-catenin and. 7 novel genes in colorectal cancers. Results The efficiency of GetUni was successfully validated by Xprofiler and RT-PCR. Genes in library N, IBD and A were all found in library T. A total of 14,879 genes were identified with 2,355 of them having at least 2 transcripts. Differences in gene enrichment among these libraries were statistically significant in 50 signal transduction pathways and Pfam protein domains by GOTM analysis P Conclusion Colorectal cancers are genetically heterogeneous. Transcription variants are common in them. Aberrations of ribosome and glycolysis pathway might be early indicators of precursor lesions in colon cancers. The electronic gene expression profile could be used to highlight the integral molecular events in colorectal cancers.

  16. Distinct Gene Expression Signatures in Lynch Syndrome and Familial Colorectal Cancer Type X

    DEFF Research Database (Denmark)

    Valentin, Mev; Therkildsen, Christina; Veerla, Srinivas

    2013-01-01

    Heredity is estimated to cause at least 20% of colorectal cancer. The hereditary nonpolyposis colorectal cancer subset is divided into Lynch syndrome and familial colorectal cancer type X (FCCTX) based on presence of mismatch repair (MMR) gene defects.......Heredity is estimated to cause at least 20% of colorectal cancer. The hereditary nonpolyposis colorectal cancer subset is divided into Lynch syndrome and familial colorectal cancer type X (FCCTX) based on presence of mismatch repair (MMR) gene defects....

  17. Family history and survival after colorectal cancer diagnosis.

    Science.gov (United States)

    Bass, Adam J; Meyerhardt, Jeffrey A; Chan, Jennifer A; Giovannucci, Edward L; Fuchs, Charles S

    2008-03-15

    A history of colorectal cancer in a first-degree relative is a recognized risk factor for developing this malignancy. The influence of a family history of colorectal cancer on survival after a diagnosis of colorectal cancer was examined in a large cohort of women. We analyzed data from 1001 women diagnosed with colorectal cancer while participating in a prospective cohort study. Data on family history were obtained before cancer diagnosis. We computed Cox proportional hazards for cancer-specific and overall mortality according to a family history of colorectal cancer, adjusting for other predictors for survival. Before diagnosis, 16% of colorectal patients reported a history of colorectal cancer in a first-degree relative. Patients with a history of colorectal cancer in 1 or more first-degree relatives experienced an adjusted hazard ratio (HR) for overall mortality of 1.32 (95% confidence interval [CI], 1.01-1.72) and colorectal cancer-specific mortality of 1.38 (95% CI, 1.02-1.86) when compared with those without a family history. Moreover, patients with 2 or more affected relatives had an HR for overall mortality of 2.07 (95% CI, 1.14-3.76) and cancer-specific mortality of 2.19 (95% CI, 1.10-4.38). The significant deleterious effect of family history was limited to patients with advanced disease at presentation and cancers originating in the colon. Among women with colorectal cancer, a history of colorectal cancer in a first-degree relative was associated with a significant decrease in survival. Additional study is needed to validate these findings and determine whether specific germline polymorphisms correlate with clinical outcomes. Copyright (c) 2008 American Cancer Society.

  18. Fusobacterium and colorectal cancer: causal factor or passenger? Results from a large colorectal cancer screening study.

    Science.gov (United States)

    Amitay, Efrat L; Werner, Simone; Vital, Marius; Pieper, Dietmar H; Höfler, Daniela; Gierse, Indra-Jasmin; Butt, Julia; Balavarca, Yesilda; Cuk, Katarina; Brenner, Hermann

    2017-08-01

    Colorectal cancer is a leading cause of morbidity and mortality worldwide in both men and women. The gut microbiome is increasingly recognized as having an important role in human health and disease. Fusobacterium has been identified in former studies as a leading gut bacterium associated with colorectal cancer, but it is still not clear if it plays an oncogenic role. In the current study, fecal samples were collected prior to bowel preparation from participants of screening colonoscopy in the German BliTz study. Using 16S rRNA gene analysis, we examined the presence and relative abundance of Fusobacterium in fecal samples from 500 participants, including 46, 113, 110 and 231 individuals with colorectal cancer, advanced adenomas, non-advanced adenomas and without any neoplasms, respectively. We found that the abundance of Fusobacterium in feces was strongly associated with the presence of colorectal cancer (P-value colorectal cancer development. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. Cancer in numbers: Do preventive measures for colorectal cancer apply?

    OpenAIRE

    Pedro J. Tárraga López; José A. Rodríguez Montes; Juan Solera Albero; Almudena Tárraga Marcos

    2017-01-01

    Abstract: Introduction: Cancer is a global problem as it will affect one in three men and one in four women during their lifetime. Colorectal cancer (CRC) is the second most common cancer in men, after lung cancer, and is the second most common cancer in women after breast cancer. It is also the second leading cause of death in men and women separately, and is the second most common cause of cancer death if both genders are considered together. CRC accounts for approximately 10% of cancer...

  20. Dermatomyositis and colorectal cancer: a systematic review.

    Science.gov (United States)

    Gkegkes, Ioannis D; Minis, Evelyn E; Iavazzo, Christos

    2017-11-22

    Dermatomyositis (DM) is an idiopathic inflammatory myositis. The principal characteristics are cutaneous rash, muscle ache, and muscle weakness. In the past, associations have been established between DM and malignancy, including colorectal cancer. A systematic PubMed and Scopus search was conducted. The median age of the patients was 65 years (range 40-82). The majority were female (17 out of 27, 63%). Adenocarcinoma was the most frequent histological type of colorectal neoplasm. DM manifested before the diagnosis of colorectal cancer in 21 out of 27 patients (77.8%). At the time of the first presentation, creatine kinase was at a median level of 514.5 U/L (range 50-11,744), and serum antibodies were present in 11 out of 27 patients (40.7%). Immediate improvement of DM symptoms after surgery occurred in 14 out of 26 patients (53.8%). Recurrence of cancer in the form of distal metastasis was present in 5 out of 26 patients (19.2%). Cancer recurrence occurred within a median of 7.9 months (range 2-21) after surgery. In 7 out of 26 patients (26.9%), DM symptoms recurred during the post-operative period. Death was reported in 23 out of 27 patients (85.2%). It is of paramount importance to perform a systematic diagnostic workup for malignancy, always including colonoscopy, in DM patients, since there is a high incidence of cancer in DM patients. Surgical treatment of colorectal tumors should precede the treatment of DM, as DM will frequently regress after a successful resection of malignancy.

  1. 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 ...

  2. Barriers to colorectal cancer screening in Asia: A systematic review ...

    African Journals Online (AJOL)

    Purpose: Colorectal cancer (CRC) is among the top five cancers afflicting both men and women globally. Once predominantly a Western disease, it has begun to rise in Asian countries as well. This systematic review aims to compile and analyze the various barriers towards colorectal cancer screening in Asia, and to ...

  3. Colorectal Cancer: Late Presentation and Outcome of Treatment ...

    African Journals Online (AJOL)

    Background: Colorectal cancer remains a major health problem especially in developed countries where it ranks as the third most common cause of cancer in both men and women. Though incidence of colorectal cancer is low in Nigeria and other developing countries, outcome of treatment remains poor due largely to late ...

  4. Presentation of colorectal cancers in Benin-City, Nigeria | Eze ...

    African Journals Online (AJOL)

    Background: Colorectal cancer is a major cause of cancer death worldwide, and the prevalence in Nigeria appears to be increasing due to a shift to western diets. We undertook a retrospective analysis of colorectal cancers seen at the University of Benin Teaching Hospital, Benin City from January 1983 to December 2002.

  5. HEREDITARY COLORECTAL CANCER REGISTRY: A CLEVELAND CLINIC FOUNDATION EXPERIENCE

    Directory of Open Access Journals (Sweden)

    J Church, MBCHB

    2017-07-01

    SUMMARY: the Cleveland Clinic approach to hereditary colorectal cancer is described. This is multidisciplinary, involving several specialties and both genetic counseling and mental health services within the registry.

  6. Improving colorectal cancer screening: fact and fantasy

    Science.gov (United States)

    Van Dam, Jacques

    2008-02-01

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

  7. The Novel Long Noncoding RNA TUSC7 Inhibits Proliferation by Sponging MiR-211 in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Jian Xu

    2017-02-01

    Full Text Available Background/Aims: The novel long noncoding RNA (lncRNA tumor suppressor candidate 7 (TUSC7 has been reported as a potential tumor suppressor, while the functional role of TUSC7 is still unknown in colorectal cancer (CRC. Here, we characterized TUSC7 expression profile in CRC patients and investigated its biological function and potential molecular mechanism. Methods: RNA isolation, qRT-PCR, cell counter kit-8 assay, cell cycle assay, EdU assay, and western blot were performed. Statistical analyses were performed using SPSS 18.0 software and p value < 0.05 was considered as statistically significant. Results: In a cohort of CRC patients, we found TUSC7 was significantly downregulated in CRC tissues compared with adjacent non-tumor tissues (P < 0.01. Patients with high expression of TUSC7 had better survival than those with low expression of TUSC7 (HR = 0.342, 95% CI: 0.120-0.972, P = 0.044. Cell count kit 8 and EdU assays showed that ectopic expression of TUSC7 in HCT116 and SW480 cells significantly inhibited cell proliferation rate. After silence of TUSC7 with small interfering RNA, cell proliferation rate increased. Flow cytometry analyses revealed cycles were arrested at G1 phase after TUSC7 overexpression. We found there were 2 binding sites of miR-211-3p within the sequence of TUSC7 and TUSC7 expression level was negatively correlated with miR-211-3p. TUSC7 overexpression increased the expression level of CDK6, which is a downstream target of miR-211-3p, in both RNA and protein level. Furthermore, luciferase reporter assay indicated that TUSC7 could sponge miR-211-3p. Conclusion: To summary, we demonstrated that TUSC7 is a potential tumor suppressor in CRC, and TUSC7 could inhibit CRC cell proliferation by completely sponging miR-211-3p.

  8. Family history of colorectal cancer is not associated with colorectal cancer survival regardless of microsatellite instability status.

    Science.gov (United States)

    Phipps, Amanda I; Ahnen, Dennis J; Campbell, Peter T; Win, Aung Ko; Jenkins, Mark A; Lindor, Noralane M; Gryfe, Robert; Potter, John D; Newcomb, Polly A

    2014-08-01

    Individuals with a family history of colorectal cancer in first-degree relatives have an elevated risk of developing colorectal cancer themselves, particularly colorectal cancer exhibiting high microsatellite instability (MSI-high). Given that MSI-high colorectal cancer is associated with a favorable prognosis, it is plausible that having a family history of colorectal cancer could, in turn, be favorably associated with colorectal cancer survival. This study comprised N = 4,284 incident colorectal cancer cases enrolled in the Colon Cancer Family Registry via population-based cancer registries. Using Cox proportional hazards regression, we evaluated the association between family history and both overall and disease-specific survival, accounting for MSI status and tumor site via stratified analyses and statistical adjustment. There was no evidence of association between family history and overall [hazard ratio (HR), 0.92; 95% confidence interval (CI), 0.79-1.08] or disease-specific survival (HR, 1.03; 95% CI, 0.85-1.24) for all cases combined, after adjustment for MSI status or tumor site. Only for rectal cancer cases was colorectal cancer family history modestly associated with more favorable overall survival (HR, 0.75; 95% CI, 0.56-0.99). Although individuals with a family history of colorectal cancer were more likely to have MSI-high tumors than those with nonfamilial disease, this did not translate to a survival benefit. Overall, there is no evidence that family history of colorectal cancer is associated with colorectal cancer survival; however, specific mechanisms underlying family history may have prognostic impact and merit further study. ©2014 American Association for Cancer Research.

  9. Colorectal Cancer Treatment in Older Patients

    OpenAIRE

    Sanoff, Hanna K.; Goldberg, Richard M.

    2007-01-01

    The burden of colorectal cancer (CRC) morbidity and mortality falls largely on the elderly, who make up more than 70% of CRC patients. Recent evidence from pooled analyses suggests that both adjuvant and palliative chemotherapy are as efficacious in fit older patients as in younger patients. Although severe hematologic toxicity is increased in older age groups treated with chemotherapy, this does not appear to increase the risk of other severe adverse events. Little evidence is available to g...

  10. Signature Celebration of Gastroenterology, Colorectal Cancer.

    Science.gov (United States)

    Chan, Andrew T; Moayyedi, Paul

    2017-11-23

    Gastroenterology has published many seminal articles that have transformed our understanding of colorectal cancer (CRC) as well as being influential in promoting colorectal cancer screening which has saved many people from developing the disease. CRC has a hereditary component most notably highlighted in Lynch syndrome. A key paper reported that the majority of mutations in patients with hereditary nonpolyposis colorectal cancer harbored mutations in the MLH1 or MSH2 mismatch repair proteins. Continuing on the gene mutation theme, another paper. highlighted that serrated polyps accounted for approximately 9% of all colon polyps and the majority of these harbored BRAF mutations, a mutation rarely seen in the traditional adenoma to carcinoma sequence. The journal also published key work outlining the role of COX-2 in the development of CRC and this led to the concept that CRC may be prevented by COX-2 inhibition. Gastroenterology has published many influential guidelines to promote screening for colorectal cancer. Initially Gastroenterology guidelines emphasized the need for offering any screening modality either alone or in combination such as fecal occult blood test, flexible sigmoidoscopy, CT colography or colonoscopy. These guidelines were very influential in persuading governments around the world of the importance of CRC and now many countries in the developed world offer national CRC screening programs. More recently guidelines have emphasized the need to offer screening programs that prevent CRC as well as early detection and colonoscopy would be the gold standard approach. Gastroenterology has also led the way in developing the concept of developing quality measures. The journal has published evidence as to which measures lead to improvement in adenoma detection and reduced interval CRC rates. These papers have been instrumental in current recommendations on quality colonoscopy practice. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights

  11. Emerging role for colorectal cancer screening in Asian countries.

    Science.gov (United States)

    John, Anil; Al Kaabi, Saad; Dweik, Nazeeh; Yakoub, Rafie; John, Anjum; Al Mohannadi, Muneera; Sharma, Manik; Wani, Hamid; Butt, M T; Derbala, M F; Rasul, Kakil; Al Qahtani, Durraiya; Taher, Mona; Al Sada, Hayam; Suleiman, Jamal; Ghanem, Issa; Abdulla, Farida

    2014-01-01

    Colorectal cancer (CRC) is one of the leading causes of cancer related mortality globally. Though Asia has traditionally been considered a relatively low incidence area for colorectal cancer, the incidence is reportedly increasing. The Asia Pacific Working Group for Colorectal Cancer has recommended screening of individuals at average risk starting from 50 years of age. Based on these recommendations we conducted a pilot study to assess the need and feasibility of a colorectal cancer screening program in the state of Qatar. We screened 1385 individuals by fecal immunochemical testing for occult blood, at the primary health center level and positive cases were referred for colonoscopy. Among those who tested positive for fecal occult blood, we picked up five patients with cancers and seven with neoplastic polyps. Our results compare with the yield of screening programs in western countries thus suggesting an emerging role for colorectal cancer screening in Asian countries.

  12. Preclinical evaluation of destruxin B as a novel Wnt signaling target suppressing proliferation and metastasis of colorectal cancer using non-invasive bioluminescence imaging

    Energy Technology Data Exchange (ETDEWEB)

    Yeh, Chi-Tai [Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan (China); Center of Excellence for Cancer Research, Taipei Medical University, Taipei, Taiwan (China); Department of Surgery, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan (China); Rao, Yerra Koteswara [Institute of Biochemical Sciences and Technology, Chaoyang University of Technology, Taichung, Taiwan (China); Ye, Min [Department of Natural Medicine, School of Pharmaceutical Sciences, Peking University, Beijing (China); Wu, Wen-Shi [Department of Horticulture and Biotechnology, Chinese Culture University, Taipei, Taiwan (China); Chang, Tung-Chen [Department of Surgery, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan (China); Wang, Liang-Shun [Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan (China); Division of Thoracic Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan (China); Wu, Chih-Hsiung [Center of Excellence for Cancer Research, Taipei Medical University, Taipei, Taiwan (China); Department of Surgery, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan (China); Wu, Alexander T.H., E-mail: chaw1211@tmu.edu.tw [Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan (China); Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan (China); Tzeng, Yew-Min, E-mail: ymtzeng@cyut.edu.tw [Institute of Biochemical Sciences and Technology, Chaoyang University of Technology, Taichung, Taiwan (China)

    2012-05-15

    In continuation to our studies toward the identification of direct anti-cancer targets, here we showed that destruxin B (DB) from Metarhizium anisopliae suppressed the proliferation and induced cell cycle arrest in human colorectal cancer (CRC) HT29, SW480 and HCT116 cells. Additionally, DB induced apoptosis in HT29 cells by decreased expression level of anti-apoptotic proteins Bcl-2 and Bcl-xL while increased pro-apoptotic Bax. On the other hand, DB attenuated Wnt-signaling by downregulation of β-catenin, Tcf4 and β-catenin/Tcf4 transcriptional activity, concomitantly with decreased expression of β-catenin target genes cyclin D1, c-myc and survivin. Furthermore, DB affected the migratory and invasive ability of HT29 cells through suppressed MMPs-2 and -9 enzymatic activities. We also found that DB targeted the MAPK and/or PI3K/Akt pathway by reduced expression of Akt, IKK-α, JNK, NF-κB, c-Jun and c-Fos while increased that of IκBα. Finally, we demonstrated that DB inhibited tumorigenesis in HT29 xenograft mice using non-invasive bioluminescence technique. Consistently, tumor samples from DB-treated mice demonstrated suppressed expression of β-catenin, cyclin D1, survivin, and endothelial marker CD31 while increased caspase-3 expression. Collectively, our data supports DB as an inhibitor of Wnt/β-catenin/Tcf signaling pathway that may be beneficial in the CRC management. Highlights: ► Destruxin B (DB) inhibited colorectal cancer cells growth and induced apoptosis. ► MAPK and/or PI3K/Akt cascade cooperates in DB induced apoptosis. ► DB affected the migratory and invasive ability of HT29 cells through MMP-9. ► DB attenuated Wnt-signaling components β-catenin, Tcf4. ► DB attenuated cyclin D1, c-myc, survivin and tumorigenesis in HT29 xenograft mice.

  13. Antisense gene therapy using anti-k-ras and antitelomerase oligonucleotides in colorectal cancer Eficacia de la terapia génica antisentido utilizando oligonucleótidos anti K-ras y antitelomerasa en cáncer colorrectal

    Directory of Open Access Journals (Sweden)

    S. Lledó

    2005-07-01

    Full Text Available Aim: to test the efficacy of anti-k-ras and antitelomerase oligonucleotides for disabling colorectal cancer cell growth. Material and methods: an established human colorectal cancer cell line (SW 480, ATTC® was used. Oligodeoxiribonucleotides (ODNs have a phosphorotioate modification to ensure intracellular intake. We used an antitelomerase ODN (Telp5 and two anti-k-ras ODNs (AS-KRAS and ISIS. AS-KRAS is designed to join the k-ras oncogene's exon 1. ISIS links to the terminal transcription unit 5' of k-ras. Telp5 joins the template region of the hTR telomerase subunit. ODNs have been tested in different concentrations (1, 5, 10, 20 micromolar. Cell viability has been tested at 48 and 72 hours. Statistical analysis and graphic design were made with the statistical package "Analyzing Data with GraphPad Prism-1999", GraphPad Sofware Inc., San Diego CA©. We used the Student's t test for statistical analysis. Results: the lowest dose (1 µM was not effective. Using the highest dose (20 mM for 48 hours of combined AS-KRAS and Telp5 cell viability decreased to 99.67%. The rest of results varied depending on ODN type, dose, and exposure time. Conclusions: tested antisense ODNs stop colorectal cancer cell growth, and a combination of anti-telomerase and anti-k-ras is the most useful treatment. Efficacy is best with a higher dose and longer treatment period.Objetivo: evaluar la eficacia de oligonucleótidos anti k-ras y antitelomerasa para detener el crecimiento tumoral en el cáncer colorrectal. Material y métodos: se ha empleado una línea celular establecida de cáncer colorrectal humano (SW 480, ATTC®. Los oligodesoxirribonucleótidos (ODN utilizados en el presente trabajo presentan modificación fosforotioato con el fin de mejorar su estabilidad en presencia de fluidos biológicos. Hemos utilizado un ODN antitelomerasa (Telp5, y dos ODN anti k-ras (AS-KRAS e ISIS. AS-KRAS actúa en el exón 1 e ISIS actúa a nivel de la unidad terminal de

  14. TGF-β signaling alterations and susceptibility to colorectal cancer

    OpenAIRE

    Xu, Yanfei; Pasche, Boris

    2007-01-01

    In 2006, more than 55 000 patients died of colorectal cancer in the US, accounting for ∼10% of all cancer deaths. Despite significant progress in screening combined with the development of novel effective therapies, colorectal cancer ranks second to lung cancer as a cause of cancer death. Twin studies indicate that 35% of all colorectal cancers are inherited, but high-penetrance tumor susceptibility genes only account for ∼3–6% of all cases. The remainder of the unexplained familial risk is p...

  15. Serum YKL-40 and colorectal cancer

    DEFF Research Database (Denmark)

    Cintin, C; Johansen, J S; Christensen, Ib Jarle

    1999-01-01

    related to short survival. In the present study we analysed YKL-40 in preoperative sera from patients with colorectal cancer and evaluated its relation to survival. Serum YKL-40 was determined by RIA in 603 patients. Survival after operation was registered, and median follow-up time was 61 months. Three......YKL-40 is a mammalian member of the chitinase protein family. Although the function of YKL-40 is unknown, the pattern of its expression suggests a function in remodelling or degradation of extracellular matrix. High serum YKL-40 has been found in patients with recurrent breast cancer and has been...

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

    Science.gov (United States)

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

  17. Reproductive history and risk of colorectal cancer in postmenopausal women.

    Science.gov (United States)

    Zervoudakis, Alice; Strickler, Howard D; Park, Yikyung; Xue, Xiaonan; Hollenbeck, Albert; Schatzkin, Arthur; Gunter, Marc J

    2011-05-18

    There are conflicting data regarding the role of sex hormones in colorectal cancer development. Whereas clinical trials data indicate that hormone therapy use reduces the risk of colorectal cancer, data from prospective cohort studies suggest that circulating estrogen levels are positively associated with colorectal cancer risk. A surrogate measure of lifetime estrogen exposure is reproductive history. We investigated the relationship between reproductive factors and the risk of colorectal cancer. Subjects were postmenopausal women enrolled in the National Institutes of Health-American Association of Retired Persons Diet and Health Study, a cohort of 214,162 individuals (aged 50-71 years) that included 2014 incident cases of colorectal cancer that occurred over a mean follow-up of 8.2 years. Questionnaires were used to collect data on reproductive factors, including ages at menarche, birth of first child, and menopause; parity, and use of oral contraceptives. Multivariable Cox proportional hazards models were constructed to examine associations between these reproductive factors and the risk of colorectal cancer, with adjustment for established colorectal cancer risk factors. All statistical tests were two-sided. Age at menopause (≥ 55 vs colorectal cancer. Among women with no history of hormone therapy use, age at menarche (≥ 15 vs 11-12 years: HR = 0.73, 95% CI = 0.57 to 0.94; P(trend) = .02) and parity (≥ 5 children vs no children: HR = 0.80, 95% CI = 0.63 to 1.02; P(trend) = .10) were inversely associated with the risk of colorectal cancer. These data support a role for sex hormones in colorectal tumorigenesis and suggest that greater endogenous estrogen exposure may increase the risk of colorectal cancer in postmenopausal women.

  18. Vaccination with apoptosis colorectal cancer cell pulsed autologous ...

    African Journals Online (AJOL)

    user

    2011-02-18

    Feb 18, 2011 ... To investigate vaccination with apoptosis colorectal cancer (CRC) cell pulsed autologous dendritic cells. (DCs) in advanced CRC, 14 patients with advanced colorectal cancer (CRC) were enrolled and treated with DCs vaccine to assess toxicity, tolerability, immune and clinical responses to the vaccine. No.

  19. Clinical Outcomes of Colorectal Cancer in Kenya | Saidi | Annals of ...

    African Journals Online (AJOL)

    Background The incidence of colorectal cancer in Africa is increasing. True data on clinical outcomes of the disease is hampered by follow up challenges. Method Follow up data of 233 patients treated for colorectal cancer between 2005 and 2010 at various Nairobi hospitals were evaluated. The primary outcome was ...

  20. Characterization of newly established colorectal cancer cell lines ...

    Indian Academy of Sciences (India)

    We have established a series of 20 colorectal cancer cell lines and performed cytogenetic and RFLP analyses to show that the recurrent genetic abnormalities of chromosomes 1, 5, 17 and 18 associated with multistep tumorigenesis in colorectal cancer, and frequently detected as recurrent abnormalities in primary tumours, ...

  1. Characterization of newly established colorectal cancer cell lines ...

    Indian Academy of Sciences (India)

    Unknown

    2000-12-19

    Dec 19, 2000 ... We have established a series of 20 colorectal cancer cell lines and performed cytogenetic and RFLP analyses to show that the recurrent genetic abnormalities of chromosomes 1, 5, 17 and 18 associated with multistep tumori- genesis in colorectal cancer, and frequently detected as recurrent abnormalities ...

  2. Prognosis of Colorectal Cancer Patients with Elevated Endothelin-1 Concentrations

    Directory of Open Access Journals (Sweden)

    Maqsood M. Elahi

    2004-01-01

    Conclusion: Preoperative plasma big ET-1 concentrations may be useful in predicting overall survival in patients with colorectal cancer. Plasma big ET-1 concentrations may be useful in the selection of high-risk, lymph node-negative patients with colorectal cancer for adjuvant therapy.

  3. Proteome analysis of human colorectal cancer tissue using 2-D ...

    African Journals Online (AJOL)

    Proteome analysis of human colorectal cancer tissue using 2-D DIGE and tandem mass spectrometry for identification of disease-related proteins. ... African Journal of Biotechnology ... The cDNA of the differential protein was transfected into colorectal cancer cells, and the biological behavior of these cells was observed.

  4. Colorectal cancer screening awareness among physicians in Greece

    Directory of Open Access Journals (Sweden)

    Chatzimichalis Georgios

    2006-06-01

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

  5. Vaccination with apoptosis colorectal cancer cell pulsed autologous ...

    African Journals Online (AJOL)

    To investigate vaccination with apoptosis colorectal cancer (CRC) cell pulsed autologous dendritic cells (DCs) in advanced CRC, 14 patients with advanced colorectal cancer (CRC) were enrolled and treated with DCs vaccine to assess toxicity, tolerability, immune and clinical responses to the vaccine. No severe toxicity ...

  6. Social inequality in breast, lung and colorectal cancers

    DEFF Research Database (Denmark)

    Søndergaard, Grethe; Mortensen, Laust Hvas; Andersen, Anne-Marie Nybo

    2013-01-01

    To examine whether family factors shared by siblings explained the association between education and risk of lung, colorectal and breast cancer.......To examine whether family factors shared by siblings explained the association between education and risk of lung, colorectal and breast cancer....

  7. Virtual colonoscopy in stenosing colorectal cancer.

    Science.gov (United States)

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

    2009-11-09

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

  8. Epidemiology of colorectal cancer; Epidemiologie kolorektaler Tumoren

    Energy Technology Data Exchange (ETDEWEB)

    Becker, N. [Deutsches Krebsforschungszentrum Heidelberg (Germany)

    2003-02-01

    Colorectal tumors are among the most frequently encountered forms of cancer worldwide. With approximately 57,000 new cases every year, they represent the most frequent type of cancer in Germany, ranking before breast cancer (approximately 46,000) and lung cancer (approximately 37,000). Although global incidence is on the rise, in Germany it is only increasing among men, but not among women. The mortality rate (approximately 26,500 deaths annually) in Germany has declined among men for about the past 10 years and among women for about the past 20 years.The most important risk factors are familial history of colorectal and other tumors as well as lifestyle factors such as nutrition, obesity, inactivity,and smoking.Lifestyle-related risks offer a broad area for implementing primary preventive measures, which have not yet been adequately exhausted. Several proven (fecal occult blood test) and probably effective (endoscopic) methods are available for secondary prevention. Consistent encouragement of these possibilities for prevention could reduce incidence and mortality substantially and render colorectal tumors less frequent. (orig.) [German] Kolorektale Tumoren gehoeren weltweit zu den haeufigsten Krebsarten und sind mit jaehrlich ca.57000 Neuerkrankungsfaellen vor Brustkrebs (ca. 46000) und Lungenkrebs (ca. 37000) die haeufigste Krebsart in Deutschland.Waehrend die Inzidenz weltweit steigt, nimmt sie in Deutschland nur bei Maennern,nicht aber bei Frauen zu.Die Mortalitaet (jaehrlich ca.26500 Todesfaelle) geht hierzulande bei Maennern seit ca.10 Jahren, bei Frauen seit ca.20 Jahren zurueck. Die bedeutendsten Risikofaktoren sind familiaere Vorgeschichte an kolorektalen und anderen Tumoren sowie Lebensstilfaktoren wie Ernaehrung, Uebergewicht,Bewegungsmangel und Rauchen.Die lebensstilbedingten Risiken bieten breiten Raum fuer primaere Praevention, der bisher nur unzureichend ausgeschoepft ist.Auch fuer sekundaere Praevention stehen mehrere nachgewiesenermassen (Test auf

  9. Serum YKL-40 in risk assessment for colorectal cancer

    DEFF Research Database (Denmark)

    Johansen, Julia S; Christensen, Ib J; Jørgensen, Lars N

    2015-01-01

    to endoscopy due to symptoms or other risk factors for colorectal cancer. Blood samples were collected just before large bowel endoscopy. Serum YKL-40 was determined by ELISA. Serum YKL-40 was higher (P ....05-1.40; P = 0.012), whereas this was not the case for those with comorbidity (OR, 0.98; 95% CI, 0.84-1.14; P = 0.80). In conclusion, high serum YKL-40 in subjects suspected of colorectal cancer and without comorbidity associates with colorectal cancer. Determination of serum YKL-40 may be useful......The aim of the present study was to test the hypothesis that high serum YKL-40 associates with colorectal cancer in subjects at risk of colorectal cancer. We measured serum YKL-40 in a prospective study of 4,496 Danish subjects [2,064 men, 2,432 women, median age 61 years (range, 18-97)] referred...

  10. Deranged Wnt signaling is frequent in hereditary nonpolyposis colorectal cancer

    DEFF Research Database (Denmark)

    Isinger-Ekstrand, Anna; Therkildsen, Christina; Bernstein, Inge

    2011-01-01

    The Wnt signaling pathway is frequently deranged in colorectal cancer and is a key target for future preventive and therapeutic approaches. Colorectal cancers associated with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome are characterized by wide-spread microsatellite instability......, but show few gross genomic alterations. We characterized expression of the Wnt signaling pathway markers β-catenin, E-cadherin, TCF-4, and PTEN using immunohistochemical staining in colorectal cancers from individuals with HNPCC. Reduced membranous staining for β-catenin was found in 64% and for E......% of the tumors. In summary, altered expression of target molecules in the Wnt signaling pathway was demonstrated in the vast majority of the HNPCC-associated tumors, which support deranged Wnt-signaling as a central tumorigenic mechanism also in MMR defective colorectal cancer....

  11. Deranged Wnt signaling is frequent in hereditary nonpolyposis colorectal cancer

    DEFF Research Database (Denmark)

    Isinger-Ekstrand, Anna; Therkildsen, Christina; Bernstein, Inge

    2011-01-01

    The Wnt signaling pathway is frequently deranged in colorectal cancer and is a key target for future preventive and therapeutic approaches. Colorectal cancers associated with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome are characterized by wide-spread microsatellite instability......, but show few gross genomic alterations. We characterized expression of the Wnt signaling pathway markers ß-catenin, E-cadherin, TCF-4, and PTEN using immunohistochemical staining in colorectal cancers from individuals with HNPCC. Reduced membranous staining for ß-catenin was found in 64% and for E......% of the tumors. In summary, altered expression of target molecules in the Wnt signaling pathway was demonstrated in the vast majority of the HNPCC-associated tumors, which support deranged Wnt-signaling as a central tumorigenic mechanism also in MMR defective colorectal cancer....

  12. Aldolase B Overexpression is Associated with Poor Prognosis and Promotes Tumor Progression by Epithelial-Mesenchymal Transition in Colorectal Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Qingguo Li

    2017-05-01

    Full Text Available Background: Glycolysis is considered to be the root of cancer development and progression, which involved a multi-step enzymatic reaction. Our study aimed at figuring out which glycolysis enzyme participates in the development of colorectal cancer and its possible mechanisms. Methods: We firstly screened out Aldolase B (ALDOB by performing qRT-PCR arrays of glycolysis-related genes in five paired liver metastasis and primary colorectal tissues, and further detected ALDOB protein with immunohistochemistry in tissue microarray (TMA consisting of 229 samples from stage I-III colorectal cancer patients. CRISPR-Cas9 method was adopted to create knock out colon cancer cell lines (LoVo and SW480 of ALDOB. The effect of ALDOB on cell proliferation and metastasis was examined in vitro using colony formation assay as well as transwell migration and invasion assay, respectively. Results: In TMA, there was 64.6% of samples demonstrated strong intensity of ALDOB. High ALDOB expression were associated with poor overall survival and disease-free survival in both univariate and multivariate regression analyses (P<0.05. In vitro functional studies of CCK-8 demonstrated that silencing ALDOB expression significantly (P<0.05 inhibited proliferation, migration and invasion of colon cancer cells. Mechanically, silencing ALDOB activated epithelial markers and repressed mesenchymal markers, indicating inactivation of ALDOB may lead to inhibition of epithelial-mesenchymal transition (EMT. Conclusion: Upregulation of ALDOB promotes colorectal cancer metastasis by facilitating EMT and acts as a potential prognostic factor and therapeutic target in colorectal cancer.

  13. Isolation and characterization of circulating micro(nano)vesicles in the plasma of colorectal cancer patients and their interactions with tumor cells.

    Science.gov (United States)

    Stec, Małgorzata; Baj-Krzyworzeka, Monika; Baran, Jarosław; Węglarczyk, Kazimierz; Zembala, Maria; Barbasz, Jakub; Szczepanik, Antoni; Zembala, Marek

    2015-11-01

    Micro(nano)vesicles (MV) are regarded as important messengers in cell-to-cell communication. There is also evidence for their pivotal role in cancer progression. Circulating MV are of different body cells origin, including tumor cell‑derived MV (TMV) in cancer patients. Determination of circulating TMV is of importance because of their potential diagnostic and therapeutic applications. In the present study, an analysis of circulating MV in colorectal cancer (CRC) patients was undertaken. Plasma from healthy donors was used as the control. In order to define MV characteristics, two plasma fractions: obtained by sequential centrifugation at 15,000 x g (MV15) and 50,000 x g (MV50) were used for analysis. The two fractions possessed a large range of sizes: 70(80)-1,300(1,400) nm and the most common particles with sizes 70-90 nm, both in patients and controls. Atomic force microscopy images of MV50 revealed a heterogeneous population of particles with different shapes and sizes. MV15 contained an increased level of CD41+ and CD61+ particles, suggesting their platelet origin. No difference between patients and controls was observed. A more precise analysis of MV50 showed the increased level of particles expressing EGFR (HER-1/Erb B1), HER-2/neu and Mucin1 (MUC1), suggesting their tumor origin. The total level of MV50‑expressing EGFR, HER-2/neu and MUC1 was enhanced in CRC patients. MV50 both of patients and controls attached to a colon cancer cell line (SW480) and to isolated blood monocytes at 2 h and were engulfed at 24 h. This uptake showed the lack of specificity. Thus, apart from the direct delivery of MV to the tumor site by plasma, monocytes carrying MV may also be involved in their transportation. Taken together, the presented data indicate that MV15 contain mainly platelet‑derived particles, while MV50 from CRC patients are enriched in TMV. Interaction of MV with cancer cells may pin-point their role in communication between tumor cells, resulting

  14. Colorectal cancer screening with virtual colonoscopy

    Science.gov (United States)

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

    1999-05-01

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

  15. The Association of Cholelithiasis and Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    C Sărăcuț

    2014-02-01

    Full Text Available Background: In the literature there are a number of studies that suggest a possible correlation between cholelithiasis/cholecystectomy and colorectal cancer. The exposure of the colon mucosa to the action of bile acids that potentially have a carcinogenic effect due to the change in anatomy after cholecystectomy, seems to be the explanation of this association. The purpose of this paper was to search for such a correlation in our study group. Methods: We performed a retrospective cross-sectional study, analyzing the patients admitted to the First Surgical Clinic of the County Emergency Clinical Hospital Tîrgu Mureș, between January 1st, 2005 - December 31st, 2010. Analyzing the medical records, operation protocols and histopathological results, we paid attention to demographics, location of neoplasia, the time elapsed since the cholecystectomy to the discovery of neoplasia, histological types, trying to perform correlations between these parameters and the lithiasic factor. Results: Out of the 534 patients admitted and operated with the diagnosis of colorectal cancer, 15.6% (n = 83 showed a history of gallbladder stone affection. Most patients came from urban areas, the average age was 67.2 (range 39-88 years, females were more affected. The most common locations were: the sigmoid colon (26.5%, rectum (36.3% and the most common histological form was moderately differentiated adenocarcinoma. Conclusions: Similar to other studies, our work suggests a slight increase in the incidence of colorectal cancer in patients that underwent a cholecystectomy, without drawing a firm conclusion. We deem it necessary to see if diet changes of the Romanian population affect this relationship

  16. Singapore Cancer Network (SCAN) Guidelines for Systemic Therapy of Colorectal Cancer.

    Science.gov (United States)

    2015-10-01

    The SCAN colorectal cancer systemic therapy workgroup aimed to develop Singapore Cancer Network (SCAN) clinical practice guidelines for systemic therapy for colorectal cancer in Singapore. The workgroup utilised a modified ADAPTE process to calibrate high quality international evidence-based clinical practice guidelines to our local setting. Five international guidelines were evaluated-those developed by the National Comprehensive Cancer Network for colon (2014) and rectal (2014) cancer, the European Society of Medical Oncology for advanced (2012) and early (2013) cancer and the National Institute of Clinical Excellence (2011). Recommendations on systemic therapy in colorectal cancer were produced. These adapted guidelines form the SCAN Guidelines 2015 for systemic therapy of colorectal cancer.

  17. Early detection of colorectal cancer

    African Journals Online (AJOL)

    related death worldwide.[1] Although the majority of individuals who develop CRC have sporadic disease, up to 20% may have a genetic predisposition.[2] Survival is strongly related to the stage of the disease at diagnosis. Where the cancer is ...

  18. Cetuximab in treatment of metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Guren, Tormod Kyrre; Thomsen, Maria Morandi; Kure, Elin H

    2017-01-01

    BACKGROUND: The NORDIC-VII study is a randomised phase III trial of cetuximab plus continuous or intermittent fluorouracil, folinic acid, and oxaliplatin (Nordic FLOX) vs FLOX alone in first-line treatment of metastatic colorectal cancer. The present report presents an updated and final survival......, neither on progression-free nor overall survival. However, the outcomes in a subset of patients, which, after the first eight treatment cycles, received cetuximab alone, suggested a beneficial effect of cetuximab monotherapy. CONCLUSIONS: Adding cetuximab to Nordic FLOX did not provide any clinical...

  19. Alcohol intake and mortality among survivors of colorectal cancer: The Cancer Prevention Study II Nutrition Cohort.

    Science.gov (United States)

    Yang, Baiyu; Gapstur, Susan M; Newton, Christina C; Jacobs, Eric J; Campbell, Peter T

    2017-06-01

    Alcohol consumption is associated with a higher risk of colorectal cancer, but to the authors' knowledge its influence on survival after a diagnosis of colorectal cancer is unclear. The authors investigated associations between prediagnosis and postdiagnosis alcohol intake with mortality among survivors of colorectal cancer. The authors identified 2458 men and women who were diagnosed with invasive, nonmetastatic colorectal cancer between 1992 (enrollment into the Cancer Prevention Study II Nutrition Cohort) and 2011. Alcohol consumption was self-reported at baseline and updated in 1997, 1999, 2003, and 2007. Postdiagnosis alcohol data were available for 1599 participants. Of the 2458 participants diagnosed with colorectal cancer, 1156 died during follow-up through 2012. Prediagnosis and postdiagnosis alcohol consumption were not found to be associated with all-cause mortality, except for an association between prediagnosis consumption of colorectal cancer-specific mortality, although there was some suggestion of increased colorectal cancer-specific mortality with postdiagnosis drinking (RR, 1.27 [95% CI, 0.87-1.86] for current drinking of colorectal cancer. The association between postdiagnosis drinking and colorectal cancer-specific mortality should be examined in larger studies of individuals diagnosed with nonmetastatic colorectal cancer. Cancer 2017;123:2006-2013. © 2017 American Cancer Society. © 2017 American Cancer Society.

  20. Family cancer history affecting risk of colorectal cancer in a prospective cohort of Chinese women.

    Science.gov (United States)

    Murphy, Gwen; Shu, Xiao-Ou; Gao, Yu-Tang; Ji, Bu-Tian; Cook, Michael Blaise; Yang, Gong; Li, Hong Lan; Rothman, Nathaniel; Zheng, Wei; Chow, Wong-Ho

    2009-10-01

    An elevated risk of colorectal cancer has been associated with sporadic colorectal cancer in first-degree relatives, mostly in Western populations. Limited data exist from traditionally low-risk areas, such as Asia, where the prevalence of risk factors may differ. We examined the association of family history of cancer and subsequent colorectal cancer risk in a cohort of traditionally low-risk Chinese women. We followed 73,358 women in the Shanghai Women's Health Study for cancer incidence until December 2005. After an average of 7 years of follow-up, 391 women were diagnosed with colorectal cancer. We calculated hazard ratios and 95% confidence intervals using Cox proportional hazards models adjusted for age, smoking, family income, education, body mass index, physical activity, and history of diabetes. We observed a significant association between colorectal cancer risk and history of a parent being diagnosed with colorectal cancer (hazard ratio: 3.34; 95% confidence interval: 1.58, 7.06). No association was observed for colorectal cancer diagnosed among siblings. Colorectal cancer risk was not influenced by a positive family history of cancer generally or any of the other cancers investigated (lung, breast, prostate, gastric, esophageal, endometrial, ovarian, urinary tract, central nervous system, and small bowel). Our cohort results suggest that consistent with findings from Western populations, having a family history of colorectal cancer may influence colorectal cancer risk to a similar extent in a low-risk population.

  1. Ancestral susceptibility to colorectal cancer

    Czech Academy of Sciences Publication Activity Database

    Huhn, S.; Pardini, Barbara; Naccarati, Alessio; Vodička, Pavel (ed.); Hemminki, K.; Försti, A.

    2012-01-01

    Roč. 27, č. 2 (2012), s. 197-204 ISSN 0267-8357 R&D Projects: GA ČR GA310/07/1430; GA ČR GAP304/10/1286 Grant - others:EU FP7(XE) HEALTH-F4-2007-200767 Institutional research plan: CEZ:AV0Z50390512 Keywords : cancer susceptibility * molecular epidemiology * genetic susceptibility Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.500, year: 2012

  2. Syncytin immunoreactivity in colorectal cancer

    DEFF Research Database (Denmark)

    Larsen, Julie Mou; Christensen, Ib Jarle; Nielsen, Hans Jørgen

    2009-01-01

    The endogenous retroviral envelope protein syncytin is involved in cell fusions and has also been associated with immunomodulatory functions. Syncytin is currently known to be expressed in the placenta, testis and brain as well as in breast and endometrial carcinomas. Using a newly developed mono...... and the Cox proportional hazard model. Interestingly, increased syncytin expression was associated with decreased overall survival in rectal but not in colonic cancer patients. Thus, the prognostic impact of syncytin expression appears to vary with the tumor type....

  3. Colorectal cancer: from epidemiology to current treatment

    Directory of Open Access Journals (Sweden)

    Riyad Bendardaf

    2006-07-01

    Full Text Available Colorectal cancer (CRC was the second most frequent cancer in Europe in 2004, responsible for 13% (376,400 of all incident cancer cases. It is also the second most frequent cause of cancer mortality in Europe, with 11.9% (203,700 annual deaths. When localized, CRC is often a curable disease, but the overall prognosis is determined by the extent of local and particularly metastatic tumour spread. The disease outlook is relatively poor, because advanced disease is a significant cause of worldwide cancer-related mortality. Thus, estimated 5-year survival rates range from nearly 90% in stage I disease (Dukes’ A to less than 10% in patients with metastatic disease (Dukes’ D. Comprehensive cancer care in the 21st century is dependent on a multidisciplinary approach to patients with malignant disease. Large bowel cancer is no exception, as there is increasing clinical trial data supporting multimodal treatment for both localized and advanced tumours. This review will focus on important aspects in CRC including the latest treatment strategies (chemotherapy, radiotherapy and the targeted therapies.

  4. Fusobacterium nucleatum Promotes Chemoresistance to Colorectal Cancer by Modulating Autophagy.

    Science.gov (United States)

    Yu, TaChung; Guo, Fangfang; Yu, Yanan; Sun, Tiantian; Ma, Dan; Han, Jixuan; Qian, Yun; Kryczek, Ilona; Sun, Danfeng; Nagarsheth, Nisha; Chen, Yingxuan; Chen, Haoyan; Hong, Jie; Zou, Weiping; Fang, Jing-Yuan

    2017-07-27

    Gut microbiota are linked to chronic inflammation and carcinogenesis. Chemotherapy failure is the major cause of recurrence and poor prognosis in colorectal cancer patients. Here, we investigated the contribution of gut microbiota to chemoresistance in patients with colorectal cancer. We found that Fusobacterium (F.) nucleatum was abundant in colorectal cancer tissues in patients with recurrence post chemotherapy, and was associated with patient clinicopathological characterisitcs. Furthermore, our bioinformatic and functional studies demonstrated that F. nucleatum promoted colorectal cancer resistance to chemotherapy. Mechanistically, F. nucleatum targeted TLR4 and MYD88 innate immune signaling and specific microRNAs to activate the autophagy pathway and alter colorectal cancer chemotherapeutic response. Thus, F. nucleatum orchestrates a molecular network of the Toll-like receptor, microRNAs, and autophagy to clinically, biologically, and mechanistically control colorectal cancer chemoresistance. Measuring and targeting F. nucleatum and its associated pathway will yield valuable insight into clinical management and may ameliorate colorectal cancer patient outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Incidence of colorectal cancer in Kashmir valley, India.

    Science.gov (United States)

    Javid, Gul; Zargar, Showkat Ali; Rather, Shabir; Khan, Abdul Rashid; Khan, Bashir Ahmad; Yattoo, Ghulam Nabi; Shah, Altaf; Gulzar, Ghulam Mohamad; Sodhi, Jaswinder Singh; Khan, Mushtaq Ahmad; Bashir, Abid Shoukat-Deeba

    2011-02-01

    There is wide variation in the incidence of colorectal cancer globally and also within the same country among different racial or ethnic groups. The present population-based study was undertaken to determine the incidence of colorectal cancer in Kashmiri population which is non-migratory and ethnically homogeneous having stable food habits. Over a period of one year, all newly diagnosed and histological proved cases of colorectal cancer in all possible areas, where such patients are diagnosed and treated were prospectively registered. A total of 212 cases of colorectal cancers were registered; of them 113 (53.3%) originated in the colon and other 99 (46.7%) in rectum. Male to female ratio was 1.2:1. The crude incidence rate of colorectal cancer was 3.65/100,000; it was 3.78 in males, and 3.50/100,000 in females. The incidence rates for colorectal cancer in Muslims and Hindus were different. The crude incidence rate for colorectal carcinoma was highest for district Srinagar 6.19/100,000 (urban area) and lowest for district Kupwara (rural area) 1.59/100,000. The highest numbers of cases were detected in the age group 55-59 years (n = 34). The age-specific rate for colorectal carcinoma was highest in the age group 55-59 years (17.21/100,000), followed by 65-69 years (14.86/100,000). The age standardized incidence rate was 4.52/100,000 per year. The truncated age adjusted incidence rates in age group 35-64 years was 8.31/100,000; while that for colorectal carcinoma was 8.77/100,000 in males and 7.66/100,000 in females. We conclude that the incidence of colorectal cancer in Kashmir valley is similar to that reported in the rest of India.

  6. Fecal Molecular Markers for Colorectal Cancer Screening

    Directory of Open Access Journals (Sweden)

    Rani Kanthan

    2012-01-01

    Full Text Available Despite multiple screening techniques, including colonoscopy, flexible sigmoidoscopy, radiological imaging, and fecal occult blood testing, colorectal cancer remains a leading cause of death. As these techniques improve, their sensitivity to detect malignant lesions is increasing; however, detection of precursor lesions remains problematic and has generated a lack of general acceptance for their widespread usage. Early detection by an accurate, noninvasive, cost-effective, simple-to-use screening technique is central to decreasing the incidence and mortality of this disease. Recent advances in the development of molecular markers in faecal specimens are encouraging for its use as a screening tool. Genetic mutations and epigenetic alterations that result from the carcinogenetic process can be detected by coprocytobiology in the colonocytes exfoliated from the lesion into the fecal matter. These markers have shown promising sensitivity and specificity in the detection of both malignant and premalignant lesions and are gaining popularity as a noninvasive technique that is representative of the entire colon. In this paper, we summarize the genetic and epigenetic fecal molecular markers that have been identified as potential targets in the screening of colorectal cancer.

  7. Incidence of colorectal cancer in young patients

    Directory of Open Access Journals (Sweden)

    FÁBIO GUILHERME C. M. DE CAMPOS

    Full Text Available ABSTRACT Sporadic colorectal cancer (CRC is traditionally diagnosed after de sixth decade of life, although a small percentage of cases are diagnosed in patients under 40 years of age, and incidence is increasing. There exists a great volume of controversy regarding clinical outcome of young patients diagnosed with colorectal cancer (CRC when compared to elder counterparts. Our aims were to evaluate the rate of CRC in young patients, to review the pertaining literature and to discuss outcomes and clinical prognosis. A retrospective review involving patients with CRC was undertaken, focusing on age at diagnosis. The information extracted from this literature review showed a trend towards a decreased incidence in older people with an opposite effect among adolescents and young adults. Moreover, biological aggressiveness in young adults diagnosed with CRC has not been fully recognized, although it is usually diagnosed later and in association with adverse histological features. Besides that, these features don't affect outcome. These apparent increase in CRC incidence among young patients during the last decades raises the need for a greater suspicious when evaluating common symptoms in this group. Thus, educational programs should widespread information for both population and physicians to improve prevention and early diagnosis results.

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

    Science.gov (United States)

    Van Blarigan, Erin L; Meyerhardt, Jeffrey A

    2015-06-01

    This review summarizes the evidence regarding physical activity and diet after colorectal cancer diagnosis in relation to quality of life, disease recurrence, and survival. There have been extensive reports on adiposity, inactivity, and certain diets, particularly those high in red and processed meats, and increased risk of colorectal cancer. Only in the past decade have data emerged on how such lifestyle factors are associated with outcomes in colorectal cancer survivors. Prospective observational studies have consistently reported that physical activity after colorectal cancer diagnosis reduces mortality. A meta-analysis estimated that each 15 metabolic equivalent task-hour per week increase in physical activity after colorectal cancer diagnosis was associated with a 38% lower risk of mortality. No randomized controlled trials have been completed to confirm that physical activity lowers risk of mortality among colorectal cancer survivors; however, trials have shown that physical activity, including structured exercise, is safe for colorectal cancer survivors (localized to metastatic stage, during and after treatment) and improves cardiorespiratory fitness and physical function. In addition, prospective observational studies have suggested that a Western dietary pattern, high carbohydrate intake, and consuming sugar-sweetened beverages after diagnosis may increase risk of colorectal cancer recurrence and mortality, but these data are limited to single analyses from one of two US cohorts. Additional data from prospective studies and randomized controlled trials are needed. Nonetheless, on the basis of the available evidence, it is reasonable to counsel colorectal cancer survivors to engage in regular physical activity and limit consumption of refined carbohydrates, red and processed meats, and sugar-sweetened beverages. © 2015 by American Society of Clinical Oncology.

  9. Colorectal Cancer Screening in Inflammatory Bowel Disease.

    Science.gov (United States)

    Sengupta, Neil; Yee, Eric; Feuerstein, Joseph D

    2016-04-01

    Patients with long-standing ulcerative colitis (UC) or Crohn's colitis are at increased risk of developing colorectal cancer (CRC). Given that most cases of CRC are thought to arise from dysplasia, previous guidelines have recommended endoscopic surveillance with random biopsies obtained from all segments of the colon involved by endoscopic or microscopic inflammation. However, recent evidence has suggested that the majority of dysplastic lesions in patients with inflammatory disease (IBD) are visible, and data have been supportive of chromoendoscopy with targeted biopsies of visible lesions versus traditional random biopsies. This review article will discuss the risk of colon cancer in patients with IBD, as well as current recommendations for CRC screening and surveillance in patients with UC or Crohn's colitis.

  10. Probiotics, prebiotics and colorectal cancer prevention.

    Science.gov (United States)

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

    2016-02-01

    Colorectal cancer (CRC), the third major cause of mortality among various cancer types in United States, has been increasing in developing countries due to varying diet and dietary habits and occupational hazards. Recent evidences showed that composition of gut microbiota could be associated with the development of CRC and other gut dysbiosis. Modulation of gut microbiota by probiotics and prebiotics, either alone or in combination could positively influence the cross-talk between immune system and microbiota, would be beneficial in preventing inflammation and CRC. In this review, role of probiotics and prebiotics in the prevention of CRC has been discussed. Various epidemiological and experimental studies, specifically gut microbiome research has effectively improved the understanding about the role of probiotics and microbial treatment as anticarcinogenic agents. A few human studies support the beneficial effect of probiotics and prebiotics; hence, comprehensive understanding is urgent to realize the clinical applications of probiotics and prebiotics in CRC prevention. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Lifestyle and Sporadic Colorectal Cancer in India.

    Science.gov (United States)

    Sinha, Rupal; Doval, Dinesh Chandra; Hussain, Showket; Kumar, Kapil; Singh, Shivendra; Basir, Seemi Farhat; Bharadwaj, Mausumi

    2015-01-01

    The study evaluated the patient, lifestyle and tumor profile in patients undergoing upfront surgery for sporadic colorectal cancer (CRC) in Indian population. One hundred consecutive patients were included. Details related to their demographic profile, habits, signs and symptoms, tumor profile, further treatment and follow up were recorded. The majority of the patients had colonic cancer (68%), advanced tumor stage 3 and 4 (46%), moderately differentiated tumors (70%) with absence of lymphatic invasion (60%) and metastasis (90%). Correlations between tumor location and abdominal pain (p-value 0.002), bleeding per rectum (p-value food (p-value 0.040) and non vegetarian diet (p-value 0.001) and metastasis and alcohol intake (p-value 0.041) were also observed. Age and tumor grade were also correlated (p-value 0.020). Minimizing the adverse lifestyle factors can help in reducing the overall incidence of CRC in the Indian population.

  12. Role of phytochemicals in colorectal cancer prevention.

    Science.gov (United States)

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

    2015-08-21

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

  13. Pulmonary nodules and metastases in colorectal cancer

    DEFF Research Database (Denmark)

    Nordholm-Carstensen, Andreas

    2016-01-01

    in CRC. In study IV we investigated the significance of mismatch repair status (MMR) for the location of metastatic spread in a nationwide Danish cohort of patients with newly diagnosed CRC between 2010 and 2012. Deficient MMR was associated with a reduced risk of synchronous metastatic disease, however......Patients with newly diagnosed colorectal cancer (CRC) are subjected to a preoperative thoraco-abdominal CT scan to determine the cancer stage. This staging is of relevance with regard to treatment and prognosis. About 20% of the patients have distant metastatic spread at the time of diagnosis, i...... to a SPCM at follow-up, but we found no evidence that IPN should result in intensified diagnostic work-up besides routine follow-up for CRC. Study II was an analysis of the prevalence of and risk factors for SPCM in a Danish nationwide cohort of patients with newly diagnosed CRC from 2001 to 2011. SPCM were...

  14. Detection of low-abundance KRAS mutations in colorectal cancer using microfluidic capillary electrophoresis-based restriction fragment length polymorphism method with optimized assay conditions.

    Directory of Open Access Journals (Sweden)

    Huidan Zhang

    Full Text Available Constitutively active KRAS mutations have been found to be involved in various processes of cancer development, and render tumor cells resistant to EGFR-targeted therapies. Mutation detection methods with higher sensitivity will increase the possibility of choosing the correct individual therapy. Here, we established a highly sensitive and efficient microfluidic capillary electrophoresis-based restriction fragment length polymorphism (µCE-based RFLP platform for low-abundance KRAS genotyping with the combination of µCE and RFLP techniques. By using our self-built sensitive laser induced fluorescence (LIF detector and a new DNA intercalating dye YOYO-1, the separation conditions of µCE for ΦX174 HaeIII DNA marker were first optimized. Then, a Mav I digested 107-bp KRAS gene fragment was directly introduced into the microfluidic device and analyzed by µCE, in which field amplified sample stacking (FASS technique was employed to obtain the enrichment of the RFLP digestion products and extremely improved the sensitivity. The accurate analysis of KRAS statuses in HT29, LS174T, CCL187, SW480, Clone A, and CX-1 colorectal cancer (CRC cell lines by µCE-based RFLP were achieved in 5 min with picoliter-scale sample consumption, and as low as 0.01% of mutant KRAS could be identified from a large excess of wild-type genomic DNA (gDNA. In 98 paraffin-embedded CRC tissues, KRAS codon 12 mutations were discovered in 28 (28.6%, significantly higher than that obtained by direct sequencing (13, 13.3%. Clone sequencing confirmed these results and showed this system could detect at least 0.4% of the mutant KRAS in CRC tissue slides. Compared with direct sequencing, the new finding of the µCE-based RFLP platform was that KRAS mutations in codon 12 were correlated with the patient's age. In conclusion, we established a sensitive, fast, and cost-effective screening method for KRAS mutations, and successfully detected low-abundance KRAS mutations in clinical

  15. Colorectal Cancer Molecular Biology Moves Into Clinical Practice

    Science.gov (United States)

    Pritchard, Colin C.; Grady, William M.

    2010-01-01

    The promise of personalized medicine is now a clinical reality, with colorectal cancer genetics at the forefront of this next major advance in clinical medicine. This is no more evident than in the recent advances in testing of colorectal cancers for specific molecular alterations in order to guide treatment with the monoclonal antibody therapies cetuximab and panitumumab, which target the epidermal growth factor receptor (EGFR). In this review, we examine genetic mechanisms of colorectal cancer and how these alterations relate to emerging biomarkers for early detection and risk stratification (diagnostic markers), prognosis (prognostic markers), and the prediction of treatment responses (predictive markers). PMID:20921207

  16. Epidermal growth factor receptor analyses in colorectal cancer

    DEFF Research Database (Denmark)

    Spindler, Karen-Lise Garm; Lindebjerg, Jan; Nielsen, Jens Nederby

    2006-01-01

    EGFR immunohistochemistry (IHC) status is not a reliable predictive marker for response to EGFR-targeted therapies. The present study compares the EGFR status at DNA, RNA and protein level. Blood samples, corresponding normal colon and colorectal cancer tissue were collected from 199 colorectal c....... The predictive value of a combination of methods needs further evaluation in the clinical setting....

  17. Bergenin suppresses the growth of colorectal cancer cells by ...

    African Journals Online (AJOL)

    Purpose: To investigate anticancer effects of bergenin on human colorectal cancer cell lines. Methods: Human colorectal adenocarcinoma cell line HCT116 was treated with various concentrations of bergenin for 24 and 48 h. Cell viability, apoptosis, cell cycle arrest and reactive oxygen species (ROS) level were analyzed ...

  18. Epidermal growth factor receptor analyses in colorectal cancer

    DEFF Research Database (Denmark)

    Spindler, Karen-Lise Garm; Lindebjerg, Jan; Nielsen, Jens Nederby

    2006-01-01

    EGFR immunohistochemistry (IHC) status is not a reliable predictive marker for response to EGFR-targeted therapies. The present study compares the EGFR status at DNA, RNA and protein level. Blood samples, corresponding normal colon and colorectal cancer tissue were collected from 199 colorectal c...

  19. [Identification of colorectal cancer using proteomic patterns in serum].

    Science.gov (United States)

    Zhao, Guang; Gao, Chun-Fang; Song, Guo-Ying; Li, Dong-Hui; Wang, Xiu-Li

    2004-06-01

    At present there is no serological parameter with high sensitivity and specificity to diagnose colorectal cancer. This study aimed at establishing a serum protein fingerprinting technique coupled with a pattern-matching algorithm to distinguish colorectal cancer from benign colorectal diseases and healthy people. Preliminary group and test group were both random selected serum samples, which each comprises 73 cases of colorectal cancer, 31 healthy people, and 16 cases of benign colorectal diseases. The sera of the test group was combined with the surface of the IMAC3 proteinchip. Then reading data of surface enhanced laser desorption/ionization- time of flight-mass spectrometry (SELDI-TOF-MS) was analyzed by Biomarker Wizard software and Biomarker pattern software to get a classification rule of tree, which is standard configuration that can distinguish the sera of colorectal cancer patients from the sera of benign colorectal disease patients and healthy people, and the standard was approved test validity by double-blindly in the test group. At the key M/Z values of 4 467 Da, 8 131 Da, 8 939 Da, 9 192 Da, 9 134 Da, 8 221 Da, 5 928 Da, 8 324 Da, 11 732 Da, protein contents of the three classes in preliminary group are obviously different by the software analysis. And the classification rule of tree was discovered, and corresponding correct ratio was 98.33% (118/120), corresponding sensitivity was 97.26% (71/73) and corresponding specificity was 100% (47/47); after double-blind examining the test group with that rule, the corresponding correct ratio was 96.77% (116/120),the corresponding sensitivity was 95.89% (70/73) and the corresponding specificity was 97.87%(46/47). Via comparative proteomics research in the sera of colorectal cancer patients and benign colorectal disease patients and healthy people, the group of protein was obviously different in pathological process in discovering colorectal cancer.

  20. Risk of second primary colorectal cancer among colorectal cancer cases: A population-based analysis

    Directory of Open Access Journals (Sweden)

    Kavitha P Raj

    2011-01-01

    Full Text Available Background: Patients with history of colorectal cancer (CRC are at increased risk for developing a second primary colorectal cancer (SPCRC as compared to the general population. However, the degree of risk is uncertain. Here, we attempt to quantify the risk, using data from the large population-based California Cancer Registry (CCR. Materials and Methods: We analyzed the CCR data for cases with surgically-treated colon and rectal cancer diagnosed during the period 1990-2005 and followed through up to January 2008. We excluded those patients diagnosed with metastatic disease and those in whom SPCRC was diagnosed within 6 months of the diagnosis of the primary CRC. Standardized incidence ratios (SIR with 95% confidence intervals (CI were calculated to evaluate risk as compared to the underlying population after taking into account age, sex, ethnicity, and time at risk. Results: The study cohort consisted of 69809 cases with colon cancer and 34448 with rectal cancer. Among these patients there were 1443 cases of SPCRCs. The SIR for developing SPCRC was higher in colon cancer survivors (SIR=1.4; 95% CI: 1.3 to 1.5 as compared to the underlying population. The incidence of SPCRC was also higher in females (SIR=1.5; 95% CI: 1.3 to 1.6 and Hispanics (SIR=2.0; 95% CI: 1.7 to 2.4 with primary colon cancer. The SIR for developing an SPCRC was higher only among those whose initial tumor was located in the descending colon (SIR=1.6; 95% CI: 1.3 to 2.0 and proximal colon (SIR=1.4; 95% CI: 1.3 to 1.6. Conclusions: Our results confirm that CRC patients, especially females and Hispanics, are at a higher risk of developing SPCRC than the general population. Differential SPCRC risk by colorectal tumor subsite is dependent on gender and ethnicity, underscoring the heterogeneous nature of CRC.

  1. Primary and Secondary Prevention of Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Pedro J. Tárraga López

    2014-07-01

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

  2. Epigenetic Alterations in Colorectal Cancer: Emerging Biomarkers

    Science.gov (United States)

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

    2015-01-01

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

  3. Molecularly targeted drugs for metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Cheng YD

    2013-11-01

    Full Text Available Ying-dong Cheng, Hua Yang, Guo-qing Chen, Zhi-cao Zhang Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China Abstract: The survival rate of patients with metastatic colorectal cancer (mCRC has significantly improved with applications of molecularly targeted drugs, such as bevacizumab, and led to a substantial improvement in the overall survival rate. These drugs are capable of specifically targeting the inherent abnormal pathways in cancer cells, which are potentially less toxic than traditional nonselective chemotherapeutics. In this review, the recent clinical information about molecularly targeted therapy for mCRC is summarized, with specific focus on several of the US Food and Drug Administration-approved molecularly targeted drugs for the treatment of mCRC in the clinic. Progression-free and overall survival in patients with mCRC was improved greatly by the addition of bevacizumab and/or cetuximab to standard chemotherapy, in either first- or second-line treatment. Aflibercept has been used in combination with folinic acid (leucovorin–fluorouracil–irinotecan (FOLFIRI chemotherapy in mCRC patients and among patients with mCRC with wild-type KRAS, the outcomes were significantly improved by panitumumab in combination with folinic acid (leucovorin–fluorouracil–oxaliplatin (FOLFOX or FOLFIRI. Because of the new preliminary studies, it has been recommended that regorafenib be used with FOLFOX or FOLFIRI as first- or second-line treatment of mCRC chemotherapy. In summary, an era of new opportunities has been opened for treatment of mCRC and/or other malignancies, resulting from the discovery of new selective targeting drugs. Keywords: metastatic colorectal cancer (mCRC, antiangiogenic drug, bevacizumab, aflibercept, regorafenib, cetuximab, panitumumab, clinical trial, molecularly targeted therapy

  4. Hereditary non-polyposis colorectal cancer : Identification of mutation carriers and assessing pathogenicity of mutations

    NARCIS (Netherlands)

    Niessen, RC; Sijmons, RH; Berends, MJW; Ou, J; Hofstra, RNW; Kleibeuker, JH

    2004-01-01

    Hereditary non-polyposis colorectal cancer (HNPCC), also referred to as Lynch syndrome, is an autosomal dominantly inherited disorder that is characterized by susceptibility to colorectal cancer and extracolonic malignancies, in particular endometrial cancer. HNPCC is caused by pathogenic mutations

  5. The impact of organisational external peer review on colorectal cancer treatment and survival in the Netherlands

    NARCIS (Netherlands)

    Kilsdonk, M. J.; van Dijk, B. A. C.; Otter, R.; Siesling, S.; van Harten, W. H.

    2014-01-01

    Background: Organisational external peer review was introduced in 1994 in the Netherlands to improve multidisciplinary cancer care. We examined the clinical impact of this programme on colorectal cancer care. Methods: Patients with primary colorectal cancer were included from 23 participating

  6. Gastrins, iron homeostasis and colorectal cancer.

    Science.gov (United States)

    Kovac, Suzana; Anderson, Gregory J; Baldwin, Graham S

    2011-05-01

    The peptide hormone gastrin has been identified as a major regulator of acid secretion and a potent mitogen for normal and malignant gastrointestinal cells. The importance of gastric acid in the absorption of dietary iron first became evident 50 years ago when iron deficiency anemia was recognized as a long-term consequence of partial gastrectomy. This review summarizes the connections between circulating gastrins, iron status and colorectal cancer. Gastrins bind two ferric ions with micromolar affinity and, in the case of non-amidated forms of the hormone, iron binding is essential for biological activity in vitro and in vivo. The demonstration of an interaction between gastrin and transferrin by biochemical techniques led to the proposal that gastrins catalyze the loading of transferrin with iron. Several lines of evidence, including the facts that the concentrations of circulating gastrins are increased in mice and humans with the iron overload disease hemochromatosis and that transferrin saturation positively correlates with circulating gastrin concentration, suggest the potential involvement of gastrins in iron homeostasis. Conversely, recognition that ferric ions play an unexpected role in the biological activity of gastrins may assist in the development of useful therapies for colorectal carcinoma and other disorders of mucosal proliferation in the gastrointestinal tract. This article is part of a Special Issue entitled: 11th European Symposium on Calcium. 2011 Elsevier B.V. All rights reserved.

  7. Towards the human colorectal cancer microbiome.

    Directory of Open Access Journals (Sweden)

    Julian R Marchesi

    Full Text Available Multiple factors drive the progression from healthy mucosa towards sporadic colorectal carcinomas and accumulating evidence associates intestinal bacteria with disease initiation and progression. Therefore, the aim of this study was to provide a first high-resolution map of colonic dysbiosis that is associated with human colorectal cancer (CRC. To this purpose, the microbiomes colonizing colon tumor tissue and adjacent non-malignant mucosa were compared by deep rRNA sequencing. The results revealed striking differences in microbial colonization patterns between these two sites. Although inter-individual colonization in CRC patients was variable, tumors consistently formed a niche for Coriobacteria and other proposed probiotic bacterial species, while potentially pathogenic Enterobacteria were underrepresented in tumor tissue. As the intestinal microbiota is generally stable during adult life, these findings suggest that CRC-associated physiological and metabolic changes recruit tumor-foraging commensal-like bacteria. These microbes thus have an apparent competitive advantage in the tumor microenvironment and thereby seem to replace pathogenic bacteria that may be implicated in CRC etiology. This first glimpse of the CRC microbiome provides an important step towards full understanding of the dynamic interplay between intestinal microbial ecology and sporadic CRC, which may provide important leads towards novel microbiome-related diagnostic tools and therapeutic interventions.

  8. Colorectal Cancer "Methylator Phenotype": Fact or Artifact?

    Directory of Open Access Journals (Sweden)

    Charles Anacleto

    2005-04-01

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

  9. Primary prevention of colorectal cancer: are we closer to reality?

    LENUS (Irish Health Repository)

    Qasim, Asghar

    2012-02-01

    Colorectal cancer is one of the leading causes of morbidity and mortality worldwide. An early detection of colorectal cancer determines therapeutic outcomes, while primary prevention remains a challenge. Our aim was to review the dietary, geographical and genetic factors in the causation and their possible role in the primary prevention of colorectal cancer. Data from experimental and clinical studies and population screening programmes were analysed to determine the factors responsible for causation of colorectal cancer. The role of dietary constituents, including the consumption of fat, red meat, fibre content, alcohol consumption, and other lifestyle issues, including obesity, lack of exercise and geographical variations in cancer prevalence were reviewed. The role of genetic and lifestyle factors in causation of colorectal cancer is evident from the experimental, clinical and population-based studies. Dietary factors, including the consumption of fat, fibre, red meat and alcohol, seem to have a significant influence in this regard. The role of micronutrients, vitamins, calcium may be relevant but remain largely unclear. In conclusion, there is ample evidence favouring the role of various dietary and lifestyle factors in the aetiology of colorectal cancer. Modification of these factors is an attractive option, which is likely to help in the primary prevention and reduced disease burden.

  10. Colorectal cancer screening and prevention in women.

    Science.gov (United States)

    Chacko, Lyssa; Macaron, Carole; Burke, Carol A

    2015-03-01

    Colorectal cancer (CRC) is one of the leading cancers and cause of cancer deaths in American women and men. Females and males share a similar lifetime cumulative risk of CRC however, substantial differences in risk factors, tumor biology, and effectiveness of cancer prevention services have been observed between them. This review distills the evidence documenting the unique variation observed between the genders relating to CRC risk factors, screening and prevention. Consistent evidence throughout the world demonstrates that women reach equivalent levels of adenomas and CRC as men but it occurs nearly a decade later in life than in their male counterparts. Women have a higher proportion of tumors which are hypermethylated, have microsatellite instability and located in the proximal colon suggesting the serrated pathway may be of greater consequence in them than in men. Other CRC risk factors such as smoking, diet and obesity have been shown to have disparate effects on women which may related to interactions between estrogen exposure, body fat distribution, and the biologic underpinnings of their tumors. There is data showing the uptake, choice, and efficacy of different CRC screening methods in women is dissimilar to that in men. The mortality benefit from FOBT, sigmoidoscopy, and protection from interval CRC by colonoscopy appears to be lower in women than men. A greater understanding of these gender idiosyncrasies will facilitate an personalized approach to CRC prevention and should ultimately lead to a reduced burden of disease.

  11. Mediterranean Diet: Prevention of Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Micah G. Donovan

    2017-12-01

    Full Text Available Colorectal cancer (CRC is the third most common cancer diagnosis and the second and third leading cause of cancer mortality in men and women, respectively. However, the majority of CRC cases are the result of sporadic tumorigenesis via the adenoma–carcinoma sequence. This process can take up to 20 years, suggesting an important window of opportunity exists for prevention such as switching toward healthier dietary patterns. The Mediterranean diet (MD is a dietary pattern associated with various health benefits including protection against cardiovascular disease, diabetes, obesity, and various cancers. In this article, we review publications available in the PubMed database within the last 10 years that report on the impact of a MD eating pattern on prevention of CRC. To assist the reader with interpretation of the results and discussion, we first introduce indexes and scoring systems commonly used to experimentally determine adherence to a MD, followed by a brief introduction of the influence of the MD pattern on inflammatory bowel disease, which predisposes to CRC. Finally, we discuss key biological mechanisms through which specific bioactive food components commonly present in the MD are proposed to prevent or delay the development of CRC. We close with a discussion of future research frontiers in CRC prevention with particular reference to the role of epigenetic mechanisms and microbiome related to the MD eating pattern.

  12. CDC Vital Signs: Colorectal Cancer Tests Save Lives

    Science.gov (United States)

    ... is right for them. Know their own family history and any personal risks they may have for CRC. Encourage friends and ... Vital Signs Issue details: Colorectal Cancer Screening Test Use — United States, 2012, Morbidity and ...

  13. Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer

    NARCIS (Netherlands)

    Tol, J.; Koopman, M.; Cats, A.; Rodenburg, C.J.; Creemers, G.J.M.; Schrama, J.G.; Erdkamp, F.L.G.; Vos, A.H.; van Groeningen, C.J.; Sinnige, H.A.M.; Richel, D.J.; Voest, E.E.; Dijkstra, J.R.; Vink-Börger, M.E.; Antonini, N.F.; Mol, L.; van Krieken, J.H.J.M.; Dalesio, O.; Punt, C.J.A.

    2009-01-01

    Background: Fluoropyrimidine- based chemotherapy plus the anti - vascular endothelial growth factor (VEGF) antibody bevacizumab is standard first- line treatment for metastatic colorectal cancer. We studied the effect of adding the anti - epidermal growth factor receptor (EGFR) antibody cetuximab to

  14. Colorectal Cancer Screening (PDQ®)—Patient Version

    Science.gov (United States)

    There are five types of tests that are used to screen for colorectal cancer: fecal occult blood test, sigmoidoscopy, colonoscopy, virtual colonoscopy, and DNA stool test. Learn more about these and other tests in this expert-reviewed summary.

  15. Alcohol consumption and distinct molecular pathways to colorectal cancer

    NARCIS (Netherlands)

    Bongaerts, B.W.C.; Goeij, A.F.P.M. de; Vogel, S. de; Brandt, P.A. van den; Goldbohm, R.A.; Weijenberg, M.P.

    2007-01-01

    High alcohol consumption is related to colorectal cancer (CRC). Our objective was to study associations between alcohol consumption and risk of CRC according to characteristics of aetiological pathways: the chromosomal instability (CIN) and the microsatellite instability (MIN) pathway. We classified

  16. Colorectal cancer in South Africa: An assessment of disease ...

    African Journals Online (AJOL)

    10th revision) (ICD-10) diagnosis codes were used to identify colorectal cancer and liver and/or pulmonary metastatic disease. Procedure codes assigned to hospital admissions were used to identify type of surgical treatment. Chemotherapy ...

  17. RET is a potential tumor suppressor gene in colorectal cancer

    Science.gov (United States)

    Luo, Yanxin; Tsuchiya, Karen D.; Park, Dong Il; Fausel, Rebecca; Kanngurn, Samornmas; Welcsh, Piri; Dzieciatkowski, Slavomir; Wang, Jianping; Grady, William M.

    2012-01-01

    Cancer arises as the consequence of mutations and epigenetic alterations that activate oncogenes and inactivate tumor suppressor genes. Through a genome-wide screen for methylated genes in colon neoplasms, we identified aberrantly methylated RET in colorectal cancer. RET, a transmembrane receptor tyrosine kinase and a receptor for the GDNF-family ligands, was one of the first oncogenes to be identified and has been shown to be an oncogene in thyroid cancer and pheochromocytoma. However, unexpectedly, we found RET is methylated in 27% of colon adenomas and in 63% of colorectal cancers, and now provide evidence that RET has tumor suppressor activity in colon cancer. The aberrant methylation of RET correlates with decreased RET expression, whereas the restoration of RET in colorectal cancer cell lines results in apoptosis. Furthermore, in support of a tumor suppressor function of RET, mutant RET has also been found in primary colorectal cancer. We now show that these mutations inactivate RET, which is consistent with RET being a tumor suppressor gene in the colon. These findings suggest that the aberrant methylation of RET and the mutational inactivation of RET promote colorectal cancer formation and that RET can serve as a tumor suppressor gene in the colon. Moreover, the increased frequency of methylated RET in colon cancers compared to adenomas suggests RET inactivation is involved in the progression of colon adenomas to cancer. PMID:22751117

  18. Prognostic and Predictive Roles of KRAS Mutation in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Amanda K. Arrington

    2012-09-01

    Full Text Available The RAS gene family is among the most studied and best characterized of the known cancer-related genes. Of the three human ras isoforms, KRAS is the most frequently altered gene, with mutations occurring in 17%–25% of all cancers. In particular, approximately 30%–40% of colon cancers harbor a KRAS mutation. KRAS mutations in colon cancers have been associated with poorer survival and increased tumor aggressiveness. Additionally, KRAS mutations in colorectal cancer lead to resistance to select treatment strategies. In this review we examine the history of KRAS, its prognostic value in patients with colorectal cancer, and evidence supporting its predictive value in determining appropriate therapies for patients with colorectal cancer.

  19. Immediately modifiable risk factors attributable to colorectal cancer in Malaysia

    OpenAIRE

    Cho Naing; Pei Kuan Lai; Joon Wah Mak

    2017-01-01

    Abstract Background This study aimed to estimate potential reductions in case incidence of colorectal cancer attributable to the modifiable risk factors such as alcohol consumption, overweight and physical inactivity amongst the Malaysian population. Methods Gender specific population-attributable fractions (PAFs) for colorectal cancer in Malaysia were estimated for the three selected risk factors (physical inactivity, overweight, and alcohol consumptions). Exposure prevalence were sourced fr...

  20. Immediately modifiable risk factors attributable to colorectal cancer in Malaysia

    OpenAIRE

    Naing, Cho; Lai, Pei Kuan; Mak, Joon Wah

    2017-01-01

    Background This study aimed to estimate potential reductions in case incidence of colorectal cancer attributable to the modifiable risk factors such as alcohol consumption, overweight and physical inactivity amongst the Malaysian population. Methods Gender specific population-attributable fractions (PAFs) for colorectal cancer in Malaysia were estimated for the three selected risk factors (physical inactivity, overweight, and alcohol consumptions). Exposure prevalence were sourced from a larg...

  1. Association between CASR Polymorphisms, Calcium Intake, and Colorectal Cancer Risk

    OpenAIRE

    Kyee-Zu Kim; Aesun Shin; Jeongseon Kim; Ji Won Park; Sung Chan Park; Hyo Seong Choi; Hee Jin Chang; Dae Yong Kim; Jae Hwan Oh

    2013-01-01

    AIM: The current study aimed to assess the effect of dietary calcium intake and possible interactions with calcium-sensing receptor (CASR) gene polymorphisms on colorectal cancer risk. METHODS: A total of 420 colorectal cancer cases and 815 controls were included in the analysis. Calcium intake was investigated using a 103 item semi-quantitative food frequency questionnaire, and four single nucleotide polymorphisms (SNPs) within the CASR, rs10934578, rs12485716, rs2270916, and rs4678174, were...

  2. Screening for colorectal cancer: what fits best?

    LENUS (Irish Health Repository)

    Lee, Chun Seng

    2012-06-01

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

  3. Depression in patients with colorectal cancer.

    Science.gov (United States)

    Sehlo, Mohammad G; Al Ahwal, Mahmoud S

    2013-04-01

    Patients with colorectal cancer (CRC) experience psychological stress due to the diagnosis and the physical and social changes brought on by the illness, increasing the risk of depressive disorder. Depression causes tremendous disability and adds to the suffering that patients must already endure. It is known to alter immune and endocrine functions that affect vulnerability to CRC, its course over time, and its response to treatment. We review the prevalence of depressive symptoms and disorders worldwide and in the Kingdom of Saudi Arabia (KSA), focusing on patients with medical illness and those with CRC, in particular. We examine how often depression is diagnosed, how it is treated, and its likely course over time, and review the effects of depression on functional disability, longevity, and immune functions. Finally, we discuss research needs and make recommendations on highest priority research studies to advance our understanding of depressive disorder in CRC patients in KSA.

  4. Oxaliplatin-induced neuropathy in colorectal cancer

    DEFF Research Database (Denmark)

    Zedan, Ahmed; Hansen, Torben Frøstrup; Fex Svenningsen, Åsa

    2014-01-01

    Oxaliplatin is a chemotherapeutic agent effective against advanced colorectal cancer. Unlike with other platinum-based agents, the main side effect of oxaliplatin is polyneuropathy. Oxaliplatin-induced polyneuropathy (OIPN) has a unique profile, which can be divided into acute and chronic...... neurotoxicity. Early identification of the neurotoxicity and alterations in dose or schedule for the medication could prevent the development of chronic symptoms, which, once established, may take many months or years to resolve or even persist throughout life with a substantial effect on quality of life....... There is no doubt that the use of pharmacogenomic methods to identify genetic bases of interindividual differences in drug response has led to what is called tailoring treatment. Yet there are some challenges regarding the application of these differences. Many efforts have been made to prevent or treat OIPN...

  5. Colorectal Cancer Screening in 3 Racial Groups

    Science.gov (United States)

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

    2015-01-01

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

  6. Prognosis of lung cancer patients with a past history of colorectal cancer.

    Science.gov (United States)

    Hattori, Aritoshi; Suzuki, Kenji; Aokage, Keiju; Mimae, Takahiro; Nagai, Kanji; Tsuboi, Masahiro; Okada, Morihito

    2014-11-01

    The prognosis in lung cancer patients with a prior history of extrapulmonary cancer is controversial. In the current multicenter joint research in Japan, we focused on the relationship between a history of colorectal cancer and its prognostic impact in patients with subsequent lung cancer. Between 2000 and 2013, we designed a retrospective multicenter study at three institutes in Japan to evaluate the prognostic factors in lung cancer patients with a previous surgery for colorectal cancer. The cohorts consisted of 123/4431 lung cancer patients with/without a previous history of surgery for colorectal cancer. The median follow-up period was 6.1 years after lung cancer surgery. The 5-year overall survival in lung cancer patients with/without colorectal cancer was not significantly different, regardless of the stage of lung cancer (overall: 71.3 versus 74.7%, P = 0.1426; Stage I lung cancer: 83.3 versus 84.8%, P = 0.3779; Stage II or more lung cancer: 47.7 versus 54.4%, P = 0.1445). Based on multivariate Cox regression analysis in 4554 lung cancer patients, a past history of colorectal cancer was not a significant prognostic factor (P = 0.5335). Among the 123 lung cancer patients with colorectal cancer, age and absence of adjuvant chemotherapy for colorectal cancer were significant prognostic factors based on multivariate analysis (P = 0.0001 and 0.0236). Furthermore, there was no difference in the overall survival of lung cancer patients according to the stage of colorectal cancer (Stage I: 74.7%; Stage II/III: 66.5%, P = 0.7239). A history of antecedent colorectal cancer did not contribute to the prognosis in patients with subsequent lung cancers. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

    Directory of Open Access Journals (Sweden)

    Erik J. Groessl

    2016-01-01

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

  8. Screening patients with a family history of colorectal cancer.

    Science.gov (United States)

    Fletcher, Robert H; Lobb, Rebecca; Bauer, Mark R; Kemp, James Alan; Palmer, Richard C; Kleinman, Ken P; Miroshnik, Irina; Emmons, Karen M

    2007-04-01

    To compare screening practices and beliefs in patients with and without a clinically important family history. We mailed a brief questionnaire asking about family history and a second, longer survey asking about knowledge of and beliefs about colorectal cancer to all respondents with a family history and a random sample of respondents without a family history of colorectal cancer. We reviewed electronic medical records for screening examinations and recording of family history. One thousand eight hundred seventy of 6,807 randomly selected patients ages 35-55 years who had been continuously enrolled in a large multispecialty group practice for at least 5 years. Recognition of increased risk, screening practices, and beliefs-all according to strength of family history and patient's age. Nineteen percent of respondents reported a family history of colorectal cancer. In 11%, this history was strong enough to warrant screening before age 50 years. However, only 39% (95% CI 36, 42) of respondents under the age of 50 years said they had been asked about family history and only 45% of those with a strong family history of colorectal cancer had been screened appropriately. Forty-six percent of patients with a strong family history did not know that they should be screened at a younger age than average risk people. Medical records mentioned family history of colorectal cancer in 59% of patients reporting a family history. More efforts are needed to translate information about family history of colorectal cancer into the care of patients.

  9. Coffee Consumption and the Risk of Colorectal Cancer.

    Science.gov (United States)

    Schmit, Stephanie L; Rennert, Hedy S; Rennert, Gad; Gruber, Stephen B

    2016-04-01

    Coffee contains several bioactive compounds relevant to colon physiology. Although coffee intake is a proposed protective factor for colorectal cancer, current evidence remains inconclusive. We investigated the association between coffee consumption and risk of colorectal cancer in 5,145 cases and 4,097 controls from the Molecular Epidemiology of Colorectal Cancer (MECC) study, a population-based case-control study in northern Israel. We also examined this association by type of coffee, by cancer site (colon and rectum), and by ethnic subgroup (Ashkenazi Jews, Sephardi Jews, and Arabs). Coffee data were collected by interview using a validated, semi-quantitative food frequency questionnaire. Coffee consumption was associated with 26% lower odds of developing colorectal cancer [OR (drinkers vs. non-drinkers), 0.74; 95% confidence interval (CI), 0.64-0.86; P coffee consumption alone (OR, 0.82; 95% CI, 0.68-0.99; P = 0.04) and for boiled coffee (OR, 0.82; 95% CI, 0.71-0.94; P = 0.004). Increasing consumption of coffee was associated with lower odds of developing colorectal cancer. Compared with 2.5 servings/day (OR, 0.46; 95% CI, 0.39-0.54; P Coffee consumption may be inversely associated with risk of colorectal cancer in a dose-response manner. Global coffee consumption patterns suggest potential health benefits of the beverage for reducing the risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 25(4); 634-9. ©2016 AACR. ©2016 American Association for Cancer Research.

  10. Hereditary nonpolyposis colorectal cancer and familial colorectal cancer in Central part of Iran, Isfahan

    Directory of Open Access Journals (Sweden)

    Amin Nemati

    2012-01-01

    Full Text Available Background: There is a lack of data on familial aggregation of colorectal cancer (CRC in Iran. We aimed to deter-mine the frequency of hereditary nonpolyposis colorectal cancer (HNPCC and familial colorectal cancer (FCC and to determine the frequency of extracolonic cancers in these families in Isfahan. Methods: We reviewed documents of all patients with a pathologically confirmed diagnosis of CRC admitted to Isfa-han referral hospitals between 1995 and 2006. We also studied our CRC registry at Poursina Hakim Research Institute from 2003 to 2008. We found HNPCC and FCC families based on the Amsterdam II criteria and interviewed them for family history of CRC and extracolonic tumors. The family history was taken at least up to the second-degree relatives. Results: During 1996 to 2008, a total of 2580 CRC cases have been diagnosed. We found 14 HNPCC and 53 FCC families. Mean age of CRC at diagnosis was 48.0 ΁ 14.6 and 49.0 ΁ 13.9 years in the HNPCC and FCC families, re-spectively (p > 0.05. The total numbers of observed extracolonic tumors were 70 (21.6%; mean age = 53.6 ΁ 11.0 years and 157 (13.8%; mean age = 54.8 ΁ 18.0 years in HNPCC and FCC families, respectively (p > 0.05. CRC was respectively found in 52 and 76 members of the HNPCC and FCC families, revealing the frequency of HNPCC and FCC as 2.0% (52/2580 and 2.9% (76/2580, respectively. Conclusions: We found a relative high frequency of HNPCC (2.0% and FCC (2.9% among CRC cases in our socie-ty and high incidence of extracolonic tumors in their families. Further studies focusing on molecular basis in this field and designing a specific screening and national cancer registry program for HNPCC and FCC families should be con-ducted.

  11. Colorectal cancer through simulation and experiment

    KAUST Repository

    Kershaw, Sophie K.

    2013-06-01

    Colorectal cancer (CRC) has formed a canonical example of tumourigenesis ever since its use in Fearon and Vogelstein\\'s linear model of genetic mutation, and continues to generate a huge amount of research interest. Over time, the field has witnessed a transition from solely experimental work to the inclusion of mathematical and computational modelling. The fusion of these disciplines has the potential to provide valuable insights into oncologic processes, but also presents the challenge of uniting many diverse perspectives. Furthermore, the cancer cell phenotype defined by the \\'Hallmarks of Cancer\\' has been extended in recent times and provides an excellent basis for future research. The authors present a timely summary of the literature relating to CRC, addressing the traditional experimental findings, summarising the key mathematical and computational approaches, and emphasising the role of the Hallmarks in current and future developments. The authors conclude with a discussion of interdisciplinary work, outlining areas of experimental interest which would benefit from the insight that theoretical modelling can provide. © The institution of engineering and technology 2013.

  12. Screening of colorectal cancer: present and future.

    Science.gov (United States)

    Maida, Marcello; Macaluso, Fabio Salvatore; Ianiro, Gianluca; Mangiola, Francesca; Sinagra, Emanuele; Hold, Georgina; Maida, Carlo; Cammarota, Giovanni; Gasbarrini, Antonio; Scarpulla, Giuseppe

    2017-12-01

    Colorectal cancer (CRC) is the third most common cancer in males and second in females, and the fourth most common cause of cancer death worldwide. Currently, about 60-70% of diagnosed cases in symptomatic patients are detected at an advanced stage of disease. Earlier stage detection through the use of screening strategies would allow for better outcomes in terms of reducing the disease burden. Areas covered: The aim of this paper is to review the current published evidence from literature which assesses the performance and effectiveness of different screening tests for the early detection of CRC. Expert commentary: Adequate screening strategies can reduce CRC incidence and mortality. In the last few decades, several tests have been proposed for CRC screening. To date, there is still insufficient evidence to identify which approach is definitively superior, and no screening strategy for CRC can therefore be defined as universally ideal. The best strategy would be the one that can be economically viable and to which the patient can adhere best to over time. The latest guidelines suggest colonoscopy every 10 years or annual fecal immuno-chemical test (FIT) for people with normal risk, while for individuals with high risk or hereditary syndromes specific recommendations are provided.

  13. Coffee, colon function and colorectal cancer.

    Science.gov (United States)

    Vitaglione, Paola; Fogliano, Vincenzo; Pellegrini, Nicoletta

    2012-09-01

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

  14. Symptom burden among young adults with breast or colorectal cancer.

    Science.gov (United States)

    Sanford, Stacy D; Zhao, Fengmin; Salsman, John M; Chang, Victor T; Wagner, Lynne I; Fisch, Michael J

    2014-08-01

    Cancer incidence has increased among young adults (YAs) and survival rates have not improved compared with other age groups. Patient-reported outcomes may enhance our understanding of this vulnerable population. In a multisite prospective study, patients completed a cancer symptom inventory at the time of enrollment (T1) and 4 weeks to 5 weeks later (T2). YAs (those aged ≤ 39 years) with breast or colorectal cancer were compared with older adults (those aged ≥ 40 years) with breast or colorectal cancer with regard to symptom severity, symptom interference, changes over time, and medical care. Participants included 1544 patients with breast cancer (96 of whom were YAs) and 718 patients with colorectal cancer (37 of whom were YAs). Compared with older adults, YAs with breast cancer were more likely to report moderate/severe drowsiness, hair loss, and symptom interference with relationships at T1. YAs with colorectal cancer were more likely to report moderate/severe pain, fatigue, nausea, distress, drowsiness, shortness of breath, and rash plus interference in general activity, mood, work, relationships, and life enjoyment compared with older adults. Compared with older adults, shortness of breath, appetite, and sore mouth were more likely to improve in YAs with breast cancer; vomiting was less likely to improve in YAs with colorectal cancer. Referrals for supportive care were few, especially among patients with colorectal cancer. YAs with breast cancer were somewhat more likely to be referred to nutrition and psychiatry services than older patients. YAs reported symptom severity, symptom interference, and variations over time that were distinct from older patients. Distinctions were found to differ by diagnostic group. These findings enhance the understanding of symptom burden in YAs and inform the development of targeted interventions and future research. © 2014 American Cancer Society.

  15. Application of hyperthermia in addition to ionizing irradiation fosters necrotic cell death and HMGB1 release of colorectal tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Schildkopf, Petra, E-mail: petra.schildkopf@uk-erlangen.de [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nuernberg (Germany); Frey, Benjamin, E-mail: benjamin.frey@uk-erlangen.de [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nuernberg (Germany); Mantel, Frederick, E-mail: frederick.mantel@web.de [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nuernberg (Germany); Ott, Oliver J., E-mail: oliver.ott@uk-erlangen.de [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nuernberg (Germany); Weiss, Eva-Maria, E-mail: eva-maria.weiss@uk-erlangen.de [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nuernberg (Germany); Sieber, Renate, E-mail: renate.sieber@uk-erlangen.de [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nuernberg (Germany); Janko, Christina, E-mail: christina.janko@uk-erlangen.de [Department for Internal Medicine 3, Institute for Clinical Immunology, Friedrich-Alexander University of Erlangen-Nuernberg (Germany); Sauer, Rolf, E-mail: rolf.sauer@uk-erlangen.de [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nuernberg (Germany); Fietkau, Rainer, E-mail: rainer.fietkau@uk-erlangen.de [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nuernberg (Germany); Gaipl, Udo S., E-mail: udo.gaipl@uk-erlangen.de [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nuernberg (Germany)

    2010-01-01

    Colorectal cancer is the second leading cause of death in developed countries. Tumor therapies should on the one hand aim to stop the proliferation of tumor cells and to kill them, and on the other hand stimulate a specific immune response against residual cancer cells. Dying cells are modulators of the immune system contributing to anti-inflammatory or pro-inflammatory responses, depending on the respective cell death form. The positive therapeutic effects of temperature-controlled hyperthermia (HT), when combined with ionizing irradiation (X-ray), were the origin to examine whether combinations of X-ray with HT can induce immune activating tumor cell death forms, also characterized by the release of the danger signal HMGB1. Human colorectal tumor cells with differing radiosensitivities were treated with combinations of HT (41.5 {sup o}C for 1 h) and X-ray (5 or 10 Gy). Necrotic cell death was prominent after X-ray and could be further increased by HT. Apoptosis remained quite low in HCT 15 and SW480 cells. X-ray and combinations with HT arrested the tumor cells in the radiosensitive G2 cell cycle phase. The amount of released HMGB1 protein was significantly enhanced after combinatorial treatments in comparison to single ones. We conclude that combining X-ray with HT may induce anti-tumor immunity as a result of the predominant induction of inflammatory necrotic tumor cells and the release of HMGB1.

  16. Colorectal Cancer Profile in a Tertiary Care Centre, Bangalore, India

    Directory of Open Access Journals (Sweden)

    Sailaja Suryadevara, , , ,

    2014-05-01

    Full Text Available Introduction: Colorectal cancers are a common disease of oncological practice. A raising incidence is seen in Asian population. It is one of the cancers where screening and early diagnosis are possible. Very few articles are there about the cancer scenario in India. A study of the disease profile helps in screening, early diagnosis and management of the disease in developing countries. Aim: To study the cancer presentation in our population which can help in developing strategies for better control of disease. Material and Methods: Medical records of 171 patients registered at Kidwai Hospital from 2010 to 2012 were retrospectively reviewed. Data including age at presentation, sex, location of the cancer and stage at presentation were analyzed. Results: The male to female ratio was 1.26:1 in rectal cancer. In colon cancer the ratio was 1:1.3. The mean age at presentation was 47 years in males and 51 years in females in colorectal cancers together. Thirty eight percent of the patients were less than 45 years old. Eighty percent of the cases were rectal cancers. In 71% of rectal cancers the growth was located within 5cm from anal verge (AV. Stage III was the commonest stage of presentation. Abdominoperineal resection (APR was the commonest surgical procedure done. Inoperability was highest with lower rectal cancer. Conclusion: Younger age at presentation, low lying rectal cancers and advanced stage at presentation were observed in our study group which includes predominantly rural population. Rectal cancers are the most common cancers referred among colorectal cancers. Screening for colorectal cancers and early evaluation of symptomatic cases need to be encouraged. Patients should be educated regarding this. Screening strategies, etiopathogenesis and genetic abnormalities in colorectal cancer patients need to be defined in developing countries.

  17. Colorectal Cancer Subtypes: Developmental Origin and Microenvironmental Regulation

    NARCIS (Netherlands)

    Fessler, Evelyn; Medema, Jan Paul

    2016-01-01

    Cancer is a heterogeneous disease and many cancer types do not represent a single entity, but are composed of biologically and clinically diverse subtypes. The subtype affiliation can influence prognosis and response to therapy. Recently, a multicenter colorectal cancer (CRC) subtyping consortium

  18. The potential of statins for individualized colorectal cancer chemoprevention.

    Science.gov (United States)

    Jacobs, Rutger J; Kodach, Liudmila L; Hardwick, James C H

    2011-12-01

    Colorectal cancer is a leading cause of death by cancer in the western world. Despite major progress, even new chemotherapeutic regimens have had relatively little impact on long term survival in the approximately 50% of patients with advanced disease at presentation meaning that prevention is the only realistic way to reduce the burden of this disease. Many countries have implemented population-based screening methods to prevent colorectal cancer by the physical removal of its precursor lesion the adenoma, or to detect cancer at an earlier stage when it is amenable to surgical cure. However these programs have only been shown to reduce colorectal cancer deaths by 30% in those screened and therefore new or complimentary approaches are needed. One such approach is chemoprevention. A number of compounds have shown potential in reducing the incidence of colorectal cancer. Most widely known are NSAIDs but recently inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, also known as statins, commonly prescribed medications that lower serum cholesterol, have been shown to reduce colorectal cancer incidence. A critical issue in chemoprevention is the weighing of benefits against risks. In chemoprevention this balance is likely to be unfavourable when used in a wide unselected population even for the safest of compounds. Therapy should therefore be tailored to the individual patient. The balance will be more favourable in high risk groups such as individuals especially susceptible to neoplasia because of environmental risk factors, patients with inflammatory bowel disease, those with a hereditary predisposition and patients with a previous history of colorectal cancer or polyps. Furthermore colorectal cancer is not one disease but a heterogeneous group of diseases with different underlying molecular mechanisms. It is likely that both prevention and therapy will need to be tailored to the molecular subtype of the cancer in question. This may explain

  19. Colorectal cancer: From prevention to personalized medicine

    Science.gov (United States)

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

    2014-01-01

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

  20. Retraction statement: 'Formin-like2 regulates Rho/ROCK pathway to promote actin assembly and cell invasion of colorectal cancer' by Yuanfeng Zeng, Huijun Xie, Yudan Qiao, Jianmei Wang, Xiling Zhu, Guoyang He, Yuling Li, Xiaoli Ren, Feifei Wang, Li Liang and Yanqing Ding.

    Science.gov (United States)

    2016-07-01

    The above article in Cancer Science (doi: 10.1111/cas.12768), published online on 26 October 2015 in Wiley Online Library (http://wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Editor in Chief, Yusuke Nakamura, and Wiley Publishing Asia Pty Ltd. The retraction has been agreed as Panels +C3 and +Y27632 of SW480 Mock shown in Figure 2a appear to have been taken from the same image, Panels + C3 and +Y27632 of HT29 FMNL2 shown in Figure 2a appear to have been taken from the same image, Panels shFMNL2-1 and shmDial1-1 in Figure 3a appear to have been taken from the same image, shFMNL2-2 and shmDial1-2 in Figure 3a appear to have been taken from the same image, Panels of shFMNL2-1 + shmDial1-1 and shFMNL2-1 + shmDial1-2 of +LPA appear to have been taken from the same image, gel bands of FLAG in Figure 4e appear to have been have been manipulated by erasing gel bands. Reference Zeng Y, Xie H, Qiao Y, Wang J, Zhu X, He G, Li Y, Ren X, Wang F, Liang L, Ding Y. Formin-like2 regulates Rho/ROCK pathway to promote actin assembly and cell invasion of colorectal cancer. Cancer Sci 2015; 106: 1385-93. doi: 10.1111/cas.12768. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  1. Second primary cancers in subsites of colon and rectum in patients with previous colorectal cancer

    NARCIS (Netherlands)

    Liu, L.; Lemmens, V.E.; de Hingh, I.H.J.T.; de Vries, E.; Roukema, J.A.; van Leerdam, M.E.; Coebergh, J.W.; Soerjomataram, I.

    Background: Compared with the general population, patients with a previous colorectal cancer are at higher risk for a second colorectal cancer, but detailed risk analysis by subsite is scarce. Objective: Our goal was to investigate the risk of a second cancer in relation to subsite as a basis for

  2. Incidence and mortality of colorectal cancer in individuals with a family history of colorectal cancer.

    Science.gov (United States)

    Schoen, Robert E; Razzak, Anthony; Yu, Kelly J; Berndt, Sonja I; Firl, Kevin; Riley, Thomas L; Pinsky, Paul F

    2015-11-01

    Little is known about the change in risk conferred by family history of colorectal cancer (CRC) as a person ages. We evaluated the effect of family history on CRC incidence and mortality after 55 years of age, when the risk of early onset cancer had passed. We collected data from participants in the randomized, controlled Prostate, Lung, Colorectal and Ovarian cancer screening trial of flexible sigmoidoscopy versus usual care (55-74 years old, no history of CRC), performed at 10 US centers from 1993 to 2001. A detailed family history of colorectal cancer was obtained at enrollment, and subjects were followed for CRC incidence and mortality for up to 13 years. Among 144,768 participants, 14,961 subjects (10.3%) reported a family of CRC. Of 2090 incident cases, 273 cases (13.1%) had a family history of CRC; among 538 deaths from CRC, 71 (13.2%) had a family history of CRC. Overall, family history of CRC was associated with an increased risk of CRC incidence (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.10-1.50; P70 years of age: HR, 1.14; 95% CI, 0.93-1.45; P trend = .59). After 55 years of age, subjects with 1 FDR with CRC had only a modest increase in risk for CRC incidence and death; age of onset in the FDR was not significantly associated with risk. Individuals with ≥2 FDRs with CRC had continued increased risk in older age. Guidelines and clinical practice for subjects with a family history of CRC should be modified to align CRC testing to risk. ClinicalTrials.gov number, NCT00002540. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  3. Colorectal Cancer - What You Need to Know PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2011-07-05

    This 60 second Public Service Announcement (PSA) is based on the July, 2011 CDC Vital Signs report. Colorectal cancer kills about 50,000 men and women every year. Screening can save lives! Screening can find abnormal growths so they can be removed before turning into cancer, and can find the cancer early, when it's easiest to treat. If you're over 50, talk to your doctor about getting screened for colorectal cancer.  Created: 7/5/2011 by Centers for Disease Control and Prevention (CDC).   Date Released: 7/5/2011.

  4. Vegetarian Dietary Patterns and the Risk of Colorectal Cancers

    Science.gov (United States)

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

    2015-01-01

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

  5. Increased risk of colorectal cancer after obesity surgery.

    Science.gov (United States)

    Derogar, Maryam; Hull, Mark A; Kant, Prashant; Östlund, Magdalena; Lu, Yunxia; Lagergren, Jesper

    2013-12-01

    The purpose was to determine whether obesity surgery is associated with a long-term increased risk of colorectal cancer. Long-term cancer risk after obesity surgery is not well characterized. Preliminary epidemiological observations and human tissue biomarker studies recently suggested an increased risk of colorectal cancer after obesity surgery. A nationwide retrospective register-based cohort study in Sweden was conducted in 1980-2009. The long-term risk of colorectal cancer in patients who underwent obesity surgery, and in an obese no surgery cohort, was compared with that of the age-, sex- and calendar year-matched general background population between 1980 and 2009. Obese individuals were stratified into an obesity surgery cohort and an obese no surgery cohort. The standardized incidence ratio (SIR), with 95% confidence interval (CI), was calculated. Of 77,111 obese patients, 15,095 constituted the obesity surgery cohort and 62,016 constituted the obese no surgery cohort. In the obesity surgery cohort, we observed 70 patients with colorectal cancer, rendering an overall SIR of 1.60 (95% CI 1.25-2.02). The SIR for colorectal cancer increased with length of time after surgery, with a SIR of 2.00 (95% CI 1.48-2.64) after 10 years or more. In contrast, the overall SIR in the obese no surgery cohort (containing 373 colorectal cancers) was 1.26 (95% CI 1.14-1.40) and remained stable with increasing follow-up time. Obesity surgery seems to be associated with an increased risk of colorectal cancer over time. These findings would prompt evaluation of colonoscopy surveillance for the increasingly large population who undergo obesity surgery.

  6. BMI Is a Risk Factor for Colorectal Cancer Mortality.

    Science.gov (United States)

    Shaukat, Aasma; Dostal, Allison; Menk, Jeremiah; Church, Timothy R

    2017-09-01

    The relationship between dietary and lifestyle risk factors and long-term mortality from colorectal cancer is poorly understood. Several factors, such as obesity, intakes of red meat, and use of aspirin, have been reported to be associated with risk of colorectal cancer mortality, though these findings have not been replicated in all studies to date. In the Minnesota Colon Cancer Control Study, 46,551 participants 50-80 years old were randomly assigned to usual care (control) or annual or biennial screening by fecal occult blood testing. Colon cancer mortality was assessed after 30 years of follow-up. Dietary intake and lifestyle risk factors were assessed by questionnaire at baseline. Age [hazard ratio (HR) 1.09; 95% CI 1.07, -1.11], male sex (HR 1.25; 95% CI 1.01, 1.57), and higher body mass index (BMI) (HR 1.03; 95% CI 1.00-1.05) increased the risk of CRC mortality, while undergoing screening for CRC was associated with a reduced risk of colorectal cancer mortality (HR 0.76; 95% CI 0.61-0.94 and 0.67; 95% CI 0.53-0.83 for biennial and annual screening, respectively). Intakes of grains, meats, proteins, coffee, alcohol, aspirin, fiber, fruits, and vegetables were not associated with colorectal cancer mortality. Our study confirms the relationship between BMI and long-term colorectal cancer mortality. Modulation of BMI may reduce risk of CRC mortality.

  7. Immediately modifiable risk factors attributable to colorectal cancer in Malaysia

    Directory of Open Access Journals (Sweden)

    Cho Naing

    2017-08-01

    Full Text Available Abstract Background This study aimed to estimate potential reductions in case incidence of colorectal cancer attributable to the modifiable risk factors such as alcohol consumption, overweight and physical inactivity amongst the Malaysian population. Methods Gender specific population-attributable fractions (PAFs for colorectal cancer in Malaysia were estimated for the three selected risk factors (physical inactivity, overweight, and alcohol consumptions. Exposure prevalence were sourced from a large-scale national representative survey. Risk estimates of the relationship between the exposure of interest and colorectal cancer were obtained from published meta-analyses. The overall PAF was then estimated, using the 2013 national cancer incidence data from the Malaysian Cancer Registry. Results Overall, the mean incidence rate for colorectal cancer in Malaysia from 2008 to 2013 was 21.3 per 100,000 population, with the mean age of 61.6 years (±12.7 and the majority were men (56.6%. Amongst 369 colorectal cancer cases in 2013, 40 cases (20 men, 20 women, 10 cases (9 men, 1 woman or 20 cases (16 men,4 women would be prevented, if they had done physical exercises, could reduce their body weight to normal level or avoided alcohol consumption, assuming that these factors are causally related to colorectal cancer. It was estimated that 66 (17.8%;66/369 colorectal cancer cases (42 men, 24 women who had all these three risk factors for the last 10 years would have been prevented, if they could control these three risk factors through effective preventive measures. Conclusions Findings suggest that approximately 18% of colorectal cancer cases in Malaysia would be prevented through appropriate preventive measures such as doing regular physical exercises, reducing their body weight to normal level and avoiding alcohol consumption, if these factors are causally related to colorectal cancer. Scaling-up nationwide public health campaigns tailored to increase

  8. Immediately modifiable risk factors attributable to colorectal cancer in Malaysia.

    Science.gov (United States)

    Naing, Cho; Lai, Pei Kuan; Mak, Joon Wah

    2017-08-04

    This study aimed to estimate potential reductions in case incidence of colorectal cancer attributable to the modifiable risk factors such as alcohol consumption, overweight and physical inactivity amongst the Malaysian population. Gender specific population-attributable fractions (PAFs) for colorectal cancer in Malaysia were estimated for the three selected risk factors (physical inactivity, overweight, and alcohol consumptions). Exposure prevalence were sourced from a large-scale national representative survey. Risk estimates of the relationship between the exposure of interest and colorectal cancer were obtained from published meta-analyses. The overall PAF was then estimated, using the 2013 national cancer incidence data from the Malaysian Cancer Registry. Overall, the mean incidence rate for colorectal cancer in Malaysia from 2008 to 2013 was 21.3 per 100,000 population, with the mean age of 61.6 years (±12.7) and the majority were men (56.6%). Amongst 369 colorectal cancer cases in 2013, 40 cases (20 men, 20 women), 10 cases (9 men, 1 woman) or 20 cases (16 men,4 women) would be prevented, if they had done physical exercises, could reduce their body weight to normal level or avoided alcohol consumption, assuming that these factors are causally related to colorectal cancer. It was estimated that 66 (17.8%;66/369) colorectal cancer cases (42 men, 24 women) who had all these three risk factors for the last 10 years would have been prevented, if they could control these three risk factors through effective preventive measures. Findings suggest that approximately 18% of colorectal cancer cases in Malaysia would be prevented through appropriate preventive measures such as doing regular physical exercises, reducing their body weight to normal level and avoiding alcohol consumption, if these factors are causally related to colorectal cancer. Scaling-up nationwide public health campaigns tailored to increase physical activity, controlling body weight within normal

  9. Experiment list: SRX863777 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available e Diagnosis=unresolved 47171266,95.4,18.2,1171 GSM1598305: SW480 CENP-A pooled reps; Homo sapiens; ChIP-Seq source_name=Human colorec...tal cancer cell line || cell line=SW480 || antibody=CENP-A (Santa Cruz, sc-22787 &

  10. Meat, fish and fat intake in relation to subsite-specific risk of colorectal cancer: The Fukuoka Colorectal Cancer Study.

    Science.gov (United States)

    Kimura, Yasumi; Kono, Suminori; Toyomura, Kengo; Nagano, Jun; Mizoue, Tetsuya; Moore, Malcolm A; Mibu, Ryuichi; Tanaka, Masao; Kakeji, Yoshihiro; Maehara, Yoshihiko; Okamura, Takeshi; Ikejiri, Koji; Futami, Kitaroh; Yasunami, Yohichi; Maekawa, Takafumi; Takenaka, Kenji; Ichimiya, Hitoshi; Imaizumi, Nobutoshi

    2007-04-01

    High intake of red meat has been associated with increased risk of colorectal cancer in Western countries. There has been much interest in the role of n-3 polyunsaturated fatty acids (PUFA) in colorectal cancer prevention, but epidemiological findings are limited and inconsistent. The objective of our study was to examine associations of meat, fish and fat intake with risk of colorectal cancer, paying particular attention to the subsite within the colorectum. Data were from the Fukuoka Colorectal Cancer Study, a population-based case-control study, covering 782 cases and 793 controls. Diet was assessed by interview, using newly developed personal-computer software for registering semiquantitative food frequencies. The intake of beef/pork, processed meat, total fat, saturated fat or n-6 PUFA showed no clear association with the overall or subsite-specific risk of colorectal cancer. There was an almost significant inverse association between n-3 PUFA and the risk of colorectal cancer; the covariate-adjusted odds ratio for the highest (median 3.94 g/day) versus lowest (median 1.99 g/day) quintile of energy-adjusted intake was 0.74 (95% confidence interval 0.52-1.06, trend P=0.050). The consumption of fish and fish products was similarly inversely related to the risk although the association was not statistically significant. These associations were more evident for distal colon cancer; adjusted odds ratio for the highest versus lowest quintile of n-3 PUFA intake was 0.56 (95% confidence interval 0.34-0.92, trend P=0.02). Our findings do not support the hypothesis that consumption of red meat increases colorectal cancer risk but do suggest that high intake of fish may decrease the risk, particularly of distal colon cancer.

  11. Novel RNA variants in colorectal cancers.

    Science.gov (United States)

    Hoff, Andreas M; Johannessen, Bjarne; Alagaratnam, Sharmini; Zhao, Sen; Nome, Torfinn; Løvf, Marthe; Bakken, Anne C; Hektoen, Merete; Sveen, Anita; Lothe, Ragnhild A; Skotheim, Rolf I

    2015-11-03

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

  12. Familial colorectal cancer: Patient assessment, surveillance and surgical management.

    Science.gov (United States)

    Kennelly, R P; Gryfe, R; Winter, D C

    2017-02-01

    Germline mutations account for 5-10% of colorectal cancer. Most mutations are autosomal dominant with high penetrance and affected patients benefit greatly from appropriate treatment. This review presents the current knowledge regarding familial colorectal cancer and provides practical information based on international guidelines and the best available evidence regarding patient assessment, surveillance and surgical management. Surgeons are often the first point of contact and frequently, the main provider of care for families with cancer syndromes or patients with familial cancer. Patients with a polyposis phenotype should undergo appropriate genetic testing. In non-polyposis patients with a cancer diagnosis, tumor testing for Lynch syndrome can guide the use of genetic testing. In patients without a personal history of cancer or polyposis, a carefully obtained family history with testing of available tumor tissue or of a living relative affected by colorectal cancer informs the need for genetic testing. Surveillance and surgical management should be planned following thorough assessment of familial cancer risk. Evidence exists to provide guidance as to the surveillance strategies required, the specific indications of genetic testing and the appropriate timing of operative intervention. A carefully obtained family history with selective genetic testing should inform surveillance and surgical management in patients who have a genetic predisposition for the development of colorectal cancer. Copyright © 2016 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  13. GSTT2 promoter polymorphisms and colorectal cancer risk

    Directory of Open Access Journals (Sweden)

    Ahn Sun-A

    2007-01-01

    Full Text Available Abstract Background Glutathione S-transferases are a group of enzymes that participate in detoxification and defense mechanisms against toxic carcinogens and other compounds. These enzymes play an important role in human carcinogenesis. In the present study, we sought to determine whether GSTT2 promoter single nucleotide polymorphisms (SNPs are associated with colorectal cancer risk. Methods A total of 436 colorectal cancer patients and 568 healthy controls were genotyped for three GSTT2 promoter SNPs (-537G>A, -277T>C and -158G>A, using real-time TaqMan assay and direct sequencing. An electrophoretic mobility shift assay (EMSA was performed to determine the effects of polymorphisms on protein binding to the GSTT2 promoter. Results The -537A allele (-537G/A or A/A was significantly associated with colorectal cancer risk (OR = 1.373, p = 0.025, while the -158A allele (-158G/A or A/A was involved in protection against colorectal cancer (OR = 0.539, p = 0.032. Haplotype 2 (-537A, -277T, -158G was significantly associated with colorectal cancer risk (OR = 1.386, p = 0.021, while haplotype 4 (-537G, -277C, -158A protected against colorectal cancer (OR = 0.539, p = 0.032. EMSA data revealed lower promoter binding activity in the -537A allele than its -537G counterpart. Conclusion Our results collectively suggest that SNPs and haplotypes of the GSTT2 promoter region are associated with colorectal cancer risk in the Korean population.

  14. Clinical implications of microsatellite instability in T1 colorectal cancer.

    Science.gov (United States)

    Kang, Jeonghyun; Lee, Hak Woo; Kim, Im-kyung; Kim, Nam Kyu; Sohn, Seung-Kook; Lee, Kang Young

    2015-01-01

    The estimation of regional lymph node metastasis (LNM) risk in T1 colorectal cancer is based on histologic examination and imaging of the primary tumor. High-frequency microsatellite instability (MSI-H) is likely to decrease the possibility of metastasis to either regional lymph nodes or distant organs in colorectal cancers. This study evaluated the clinical implications of MSI in T1 colorectal cancer with emphasis on the usefulness of MSI as a predictive factor for regional LNM. A total of 133 patients who underwent radical resection for T1 colorectal cancer were included. Genomic DNA was extracted from normal and tumor tissues and amplified by polymerase chain reaction (PCR). Five microsatellite markers, BAT-25, BAT-26, D2S123, D5S346, and D17S250, were used. MSI and clinicopathological parameters were evaluated as potential predictors of LNM using univariate and multivariate analyses. Among 133 T1 colorectal cancer patients, MSI-H, low-frequency microsatellite instability (MSI-L), and microsatellite stable (MSS) colorectal cancers accounted for 7.5%, 6%, and 86.5%, respectively. MSI-H tumors showed a female predominance, a proximal location and more retrieved lymph nodes. Twenty-two patients (16.5%) had regional LNM. Lymphovascular invasion and depth of invasion were significantly associated with LNM. There was no LNM in 10 MSI-H patients; however, MSI status was not significantly correlated with LNM. Disease-free survival did not differ between patients with MSI-H and those with MSI-L/MSS. MSI status could serve as a negative predictive factor in estimating LNM in T1 colorectal cancer, given that LNM was not detected in MSI-H patients. However, validation of our result in a different cohort is necessary.

  15. Changes in apoptosis during the development of colorectal cancer : a systematic review of the literature

    NARCIS (Netherlands)

    Koornstra, JJ; de Jong, S; Hollema, H; de Vries, EGE; Kleibeuker, JH

    The development of colorectal cancer is characterised by an accumulation of molecular genetic alterations causing disorders in cell growth, differentiation and apoptosis. Although changes in apoptosis with colorectal cancer development have been studied extensively, a clear consensus of opinion has

  16. Dietary fiber intake and risk of colorectal cancer: A pooled analysis of prospective cohort studies

    NARCIS (Netherlands)

    Park, Y.; Hunter, D.J.; Spiegelman, D.; Bergkvist, L.; Berrino, F.; Brandt, P.A. van den; Buring, J.E.; Colditz, G.A.; Freudenheim, J.L.; Fuchs, C.S.; Giovannucci, E.; Goldbohm, R.A.; Graham, S.; Harnack, L.; Hartman, A.M.; Jacobs, D.R.; Kato, I.; Krogh, V.; Leitzmann, M.F.; McCullough, M.L.; Miller, A.B.; Pietinen, P.; Rohan, T.E.; Schatzkin, A.; Willett, W.C.; Wolk, A.; Zeleniuch-Jacquotte, A.; Zhang, S.M.; Smith-Warner, S.A.

    2005-01-01

    Context: Inconsistent findings from observational studies have continued the controversy over the effects of dietary fiber on colorectal cancer. Objective: To evaluate the association between dietary fiber intake and risk of colorectal cancer. Design, Setting, and Participants: From 13 prospective

  17. Role of detection of microsatellite instability in Chinese with hereditary nonpolyposis colorectal cancer or ordinary hereditary colorectal cancer.

    Science.gov (United States)

    Liu, Wen-Zhi; Jin, Feng; Zhang, Zhen-Hai; Wang, Shu-Bao

    2006-08-07

    To detect microsatellite instability (MSI) in patients with hereditary nonpolyposis colorectal cancer or ordinary hereditary colorectal cancer and to provide criteria for screening the kindreds with hereditary nonpolyposis colorectal cancer at molecular level. MSI was detected in the specimens from 20 cases with HNPCC, 20 cases with ordinary hereditary colorectal cancer and 20 cases with sporadic colorectal cancer by means of polymerase chain reaction-single strand conformation polymorphism. The positive rate of MSI was 85% (17/20) in HNPCC group, 40% (8/20) in ordinary hereditary colorectal cancer group and 10% (2/20) in the sporadic colorectal cancer group respectively. The differences were significant. The mean ages of the three groups were 43.6, 52.2, and 61.8 years respectively, which increased gradually. The incidence of right hemicolon cancer was 64.7%, 37.5%, and 0% respectively, which decreased gradually and had significant difference. The expression ratio of BAT26 and BAT25 was 94.1% respectively, which was highest in the 5 gene sites studied. The incidence of poorly differentiated adenocarcinoma was 70.6% in HNPCC group among high frequency microsatellite instability (MSI-H), which was higher than the other two groups, which had 50% and 50% respectively. The incidence of MSI-H is higher in HNPCC group. The detection of MSI is simple and economical and has high correlation with the clinicopathologic feature of HNPCC and can be used as a screening method to detect the germ line mutation of the mismatch repair gene.

  18. KRAS mutation is a predictor of oxaliplatin sensitivity in colon cancer cells.

    Directory of Open Access Journals (Sweden)

    Yu-Lin Lin

    Full Text Available Molecular biomarkers to determine the effectiveness of targeted therapies in cancer treatment have been widely adopted in colorectal cancer (CRC, but those to predict chemotherapy sensitivity remain poorly defined. We tested our hypothesis that KRAS mutation may be a predictor of oxaliplatin sensitivity in CRC. KRAS was knocked-down in KRAS-mutant CRC cells (DLD-1(G13D and SW480(G12V by small interfering RNAs (siRNA and overexpressed in KRAS-wild-type CRC cells (COLO320DM by KRAS-mutant vectors to generate paired CRC cells. These paired CRC cells were tested by oxaliplatin, irinotecan and 5FU to determine the change in drug sensitivity by MTT assay and flow cytometry. Reasons for sensitivity alteration were further determined by western blot and real-time quantitative reverse transcriptase polymerase chain reaction (qRT -PCR. In KRAS-wild-type CRC cells (COLO320DM, KRAS overexpression by mutant vectors caused excision repair cross-complementation group 1 (ERCC1 downregulation in protein and mRNA levels, and enhanced oxaliplatin sensitivity. In contrast, in KRAS-mutant CRC cells (DLD-1(G13D and SW480(G12V, KRAS knocked-down by KRAS-siRNA led to ERCC1 upregulation and increased oxaliplatin resistance. The sensitivity of irinotecan and 5FU had not changed in the paired CRC cells. To validate ERCC1 as a predictor of sensitivity for oxaliplatin, ERCC1 was knocked-down by siRNA in KRAS-wild-type CRC cells, which restored oxaliplatin sensitivity. In contrast, ERCC1 was overexpressed by ERCC1-expressing vectors in KRAS-mutant CRC cells, and caused oxaliplatin resistance. Overall, our findings suggest that KRAS mutation is a predictor of oxaliplatin sensitivity in colon cancer cells by the mechanism of ERCC1 downregulation.

  19. miR-31 affects colorectal cancer cells by inhibiting autophagy in cancer-associated fibroblasts

    Science.gov (United States)

    Zhang, Shuyu; Wu, Yong; Wu, Yongyou; Zhao, Kui; Xing, Chungen; Cao, Jianping; Zhu, Hong; Li, Ming; Ye, Zhenyu; Peng, Wei

    2016-01-01

    Autophagy is a double-edged sword in tumor development. Recent studies have found that miRNAs have an inhibitory effect on the regulation of autophagy. It has been reported that miR-31 plays an important role in the development of colorectal cancer. However, what role miR-31 plays in colorectal cancer-associated fibroblasts (CAFs) has not been determined. In this study, we confirmed that the expression of miR-31 in CAFs was higher than in normal colorectal fibroblasts (NFs). We also found that treatment of CAFs with miR-31 mimic inhibited the expression of the autophagy-related genes Beclin-1, ATG, DRAM and LC3. In addition, we found up-regulation of miR-31 significantly affected colorectal cancer cell behaviors, including proliferation, invasion and apoptosis. Also, up-regulation of miR-31 in CAF could increase the radiosensitivity of colorectal cancer cells co-cultured with CAF. In summary, miR-31 can inhibit autophagy in colorectal CAFs, affect colorectal cancer development, and increase the radiosensitivity of colorectal cancer cells co-cultured with CAF. We hypothesize that miR-31 may become a new target of treatments for colorectal cancer. PMID:27793031

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

    Directory of Open Access Journals (Sweden)

    Sherri G. Homan

    2015-08-01

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

  1. Cannabinoids and cancer: potential for colorectal cancer therapy.

    Science.gov (United States)

    Patsos, H A; Hicks, D J; Greenhough, A; Williams, A C; Paraskeva, C

    2005-08-01

    Despite extensive research into the biology of CRC (colorectal cancer), and recent advances in surgical techniques and chemotherapy, CRC continues to be a major cause of death throughout the world. Therefore it is important to develop novel chemopreventive/chemotherapeutic agents for CRC. Cannabinoids are a class of compounds that are currently used in the treatment of chemotherapy-induced nausea and vomiting, and in the stimulation of appetite. However, there is accumulating evidence that they could also be useful for the inhibition of tumour cell growth by modulating key survival signalling pathways. The chemotherapeutic potential for plant-derived and endogenous cannabinoids in CRC therapy is reviewed.

  2. Genomic Determinants of Protein Abundance Variation in Colorectal Cancer Cells

    Directory of Open Access Journals (Sweden)

    Theodoros I. Roumeliotis

    2017-08-01

    Full Text Available Assessing the impact of genomic alterations on protein networks is fundamental in identifying the mechanisms that shape cancer heterogeneity. We have used isobaric labeling to characterize the proteomic landscapes of 50 colorectal cancer cell lines and to decipher the functional consequences of somatic genomic variants. The robust quantification of over 9,000 proteins and 11,000 phosphopeptides on average enabled the de novo construction of a functional protein correlation network, which ultimately exposed the collateral effects of mutations on protein complexes. CRISPR-cas9 deletion of key chromatin modifiers confirmed that the consequences of genomic alterations can propagate through protein interactions in a transcript-independent manner. Lastly, we leveraged the quantified proteome to perform unsupervised classification of the cell lines and to build predictive models of drug response in colorectal cancer. Overall, we provide a deep integrative view of the functional network and the molecular structure underlying the heterogeneity of colorectal cancer cells.

  3. Proteinuria as a Risk Factor for Mortality in Patients with Colorectal Cancer

    OpenAIRE

    Kim, Min Jee; Kang, Yong Un; Kim, Chang Seong; Choi, Joon Seok; Bae, Eun Hui; Ma, Seong Kwon; Kweon, Sun-Seog; Kim, Soo Wan

    2013-01-01

    Purpose We investigated the effects of proteinuria and renal insufficiency on all-cause mortality in patients with colorectal cancer, with special emphasis on cancer staging and cancer-related deaths. Materials and Methods We retrospectively studied a cohort of patients with colorectal cancer. In protocol 1, patients were classified into four groups based on the operability of cancer and proteinuria: group 1, early-stage cancer patients (colorectal cancer stage ?3) without proteinuria; group ...

  4. Diagnosing lynch syndrome in absence of colorectal cancer.

    Science.gov (United States)

    Lynch, Henry T; Knezetic, Joseph; Lanspa, Stephen

    2012-11-01

    There are many ways in which a diagnosis of Lynch syndrome can be made, most prominent of which is family history, presence of cancer, high microsatellite instability, immunohistochemistry, and a mismatch repair germline mutation. There are at least four molecular pathways for colorectal cancer carcinogenesis: 1) adenoma-carcinoma sequence; 2) hereditary microsatellite instability; 3) serrated pathway; 4) epidermal growth factor receptor. The answer to diagnosing Lynch syndrome in the absence of colorectal cancer may be partially based upon the phenotypic characteristics of the colonic polyps should they be identified at colonoscopy, specifically their phenotypic characteristics of location, size, histology, number, and age of polyp onset.

  5. New Developments in Interventional Oncology: Liver Metastases From Colorectal Cancer.

    Science.gov (United States)

    Kallini, Joseph R; Gabr, Ahmed; Abouchaleh, Nadine; Ali, Rehan; Riaz, Ahsun; Lewandowski, Robert J; Salem, Riad

    Colorectal cancer is the third leading cause of cancer death in the United States. Although hepatic excision is the first-line treatment for colorectal liver metastasis (CRLM), few patients are candidates. Locoregional therapy (LRT) encompasses minimally invasive techniques practiced by interventional radiology. These include ablative treatments (radiofrequency ablation, microwave ablation, and cryosurgical ablation) and transcatheter intra-arterial therapy (hepatic arterial infusion chemotherapy, transarterial "bland" embolization, transarterial chemoembolization, and radioembolization with yttrium 90). The National Comprehensive Cancer Network recommends LRT for unresectable CRLM refractory to chemotherapy. The following is a review of LRT in CRLM, including salient features, advantages, limitations, current roles, and future considerations.

  6. Effects and Costs of Colorectal Cancer Screening and Follow-up after Polypectomy

    NARCIS (Netherlands)

    F. Loeve

    2003-01-01

    textabstractColorectal cancer is a major public health problem in many countries. In 1997, approximately 8,500 new cases of colorectal cancer were diagnosed in the Netherlands and more than 4,000 individuals died from this disease. Screening for colorectal cancer in the general population has the

  7. 42 CFR 410.37 - Colorectal cancer screening tests: Conditions for and limitations on coverage.

    Science.gov (United States)

    2010-10-01

    ... relative (sibling, parent, or child) who has had colorectal cancer or an adenomatous polyp; (ii) A family... 42 Public Health 2 2010-10-01 2010-10-01 false Colorectal cancer screening tests: Conditions for...) BENEFITS Medical and Other Health Services § 410.37 Colorectal cancer screening tests: Conditions for and...

  8. The heterogeneity of genetic predisposition to early-onset colorectal cancer

    NARCIS (Netherlands)

    Hahn, M.M.

    2016-01-01

    Colorectal cancer is one of the major causes of death in developed countries. There is a strong association between genetic factors and the risk of developing colorectal cancer. However, a large fraction of the expected heritability of colorectal cancer still remains unexplained (‘missing

  9. 78 FR 42954 - Scientific Information Request on Imaging Tests for the Staging of Colorectal Cancer

    Science.gov (United States)

    2013-07-18

    ... secondary outcomes, baseline characteristics, number of patients screened/ eligible/enrolled/lost to follow... for pretreatment staging of patients with primary and recurrent colorectal cancer? a. What is the test... colorectal cancer Adult patients with an established diagnosis of recurrent colorectal cancer Interventions...

  10. 78 FR 38716 - Scientific Information Request on Imaging Tests for the Staging of Colorectal Cancer

    Science.gov (United States)

    2013-06-27

    ... outcomes, baseline characteristics, number of patients screened/ eligible/enrolled/lost to follow-up... pretreatment staging of patients with primary and recurrent colorectal cancer? a. What is the test performance... colorectal cancer Adult patients with an established diagnosis of recurrent colorectal cancer Interventions...

  11. Surveillance for hereditary nonpolyposis colorectal cancer - A long-term study on 114 families

    NARCIS (Netherlands)

    Cappel, WHDTN; Nagengast, FM; Griffioen, G; Menko, FH; Taal, BG; Kleibeuker, JH; Vasen, HF

    2002-01-01

    PURPOSE: Hereditary nonpolyposis colorectal cancer is caused by germline mutations in DNA mismatch repair genes. Mutation carriers have a 60 to 85 percent risk of developing colorectal cancer. In the Netherlands hereditary nonpolyposis colorectal cancer families are monitored in an intensive

  12. Correlates of initiating colorectal cancer screening beginning at age 50.

    Science.gov (United States)

    Phillips, Karon L; Smith, Matthew Lee; Ahn, SangNam; Ory, Marcia G; Hochhalter, Angie K

    2013-02-01

    This study examined (a) differences in rates of initiating colorectal cancer screening across age groups, and (b) factors associated with initiation of colorectal cancer screening among persons age 50-75. Data from 1,699 adults age 50-75 were analyzed from a random sample of households in an eight-county region surrounding the Brazos Valley in Texas. Bivariate descriptive analyses were performed. Logistic regression was employed to assess relationships between demographic, health status, and healthcare utilization variables and having initiated colorectal cancer examination. Having more than a high school education (OR = 1.48, p = 0.002), having insurance (OR = 1.76, p = 0.007), being obese (OR = 1.58, p = 0.015), and having a routine health check-up within the past 2 years (OR = 3.39, p < 0.001) were associated with an increased likelihood of having a colorectal cancer examination. The findings suggest that routine interactions with health care providers may encourage persons to initiate colorectal cancer screening according to guidelines.

  13. Recognition of Depression and Anxiety among Elderly Colorectal Cancer Patients

    Directory of Open Access Journals (Sweden)

    Amy Y. Zhang

    2010-01-01

    Full Text Available This study investigated the ICD-9 diagnostic rates of depressive and anxiety disorders, including major depression, neurotic depression, adjustment disorder with depressed mood, depressive disorder NOS (not elsewhere classified, and anxiety states, among elderly Medicare beneficiaries (age ≥ 65 who received a colorectal cancer diagnosis between 1998 and 2002 in U.S. The Seer-Medicare data, representing 14–25% of the U.S. population, was used to examine ICD-9 diagnostic rates of depressive and anxiety disorders among 56,182 colorectal cancer outpatients and 265,382 noncancer outpatients, respectively. The findings show that the ICD-9 diagnoses ranged from 1.5% to 1.8% for depressive disorders and 0.8% to 1.2% for anxiety states in the colorectal cancer outpatients, and from 2% to 2.5% for depressive disorders and 1.1% to 1.5% for anxiety states in the noncancer outpatients over five years. More than 70% of colorectal cancer outpatients with a depressive diagnosis were diagnosed for depressive disorder NOS. The findings suggest that the difficulty in recognizing depressive symptoms in colorectal cancer patients may contribute in part to the low ICD-9 diagnostic rates of depressive disorders. They call for research attention to the investigation of depressive symptoms for improving the recognition and treatment in this patient population.

  14. Dietary flavonoid intake and colorectal cancer risk in the European prospective investigation into cancer and nutrition (EPIC) cohort

    NARCIS (Netherlands)

    Zamora-Ros, Raul; Barupal, Dinesh K.; Rothwell, Joseph A.; Jenab, Mazda; Fedirko, Veronika; Romieu, Isabelle; Aleksandrova, Krasimira; Overvad, Kim; Kyrø, Cecilie; Tjønneland, Anne; Affret, Aurélie; His, Mathilde; Boutron-Ruault, Marie Christine; Katzke, Verena; Kühn, Tilman; Boeing, Heiner; Trichopoulou, Antonia; Naska, Androniki; Kritikou, Maria; Saieva, Calogero; Agnoli, Claudia; Santucci de Magistris, Maria; Tumino, Rosario; Fasanelli, Francesca; Weiderpass, Elisabete; Skeie, Guri; Merino, Susana; Jakszyn, Paula; Sánchez, Maria José; Dorronsoro, Miren; Navarro, Carmen; Ardanaz, Eva; Sonestedt, Emily; Ericson, Ulrika; Maria Nilsson, Lena; Bodén, Stina; Bas Bueno-de-Mesquita, H.; Peeters, Petra H.|info:eu-repo/dai/nl/074099655; Perez-Cornago, Aurora; Wareham, Nicholas J.; Khaw, Kay Thee; Freisling, Heinz; Cross, Amanda J.; Riboli, Elio; Scalbert, Augustin

    2017-01-01

    Flavonoids have been shown to inhibit colon cancer cell proliferation in vitro and protect against colorectal carcinogenesis in animal models. However, epidemiological evidence on the potential role of flavonoid intake in colorectal cancer (CRC) development remains sparse and inconsistent. We

  15. Sulindac treatment in hereditary non-pollyposis colorectal cancer

    NARCIS (Netherlands)

    Rijcken, Fleur E. M.; Hollema, Harry; van der Zee, Ate G. J.; van der Sluis, Tineke; Ek, Wytske Boersma-van; Kleibeuker, Jan H.

    Non-steroidal anti-inflammatory drugs, e.g. sulindac have been extensively studied for chemoprevention in familial adenomatous polyposis, but not in hereditary non-polyposis colorectal cancer (HNPCC). We evaluated these effects in HNPCC using surrogate end-points for cancer risk. In a randomised

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

    Science.gov (United States)

    Hereditary colorectal cancer syndromes include Lynch syndrome and several polyposis syndromes (familial adenomatous polyposis, MUTYH-associated polyposis, juvenile polyposis syndrome, Peutz-Jeghers syndrome, and serrated polyposis syndrome). Learn about the genetics, clinical manifestations, management, and psychosocial aspects of these and other hereditary colon cancer syndromes in this expert-reviewed summary.

  17. Colorectal Cancer Screening: A Circle of Health for Alaskans

    Science.gov (United States)

    ... U.S. Preventive Services Task Force (USPSTF) recommends colorectal cancer screening for men and women aged 50-75 using high-sensitivity fecal occult blood testing (FOBT), sigmoidoscopy, or ... of colon cancer, but several other things may cause blood to ...

  18. Colorectal Cancer and Liver Metastases : determinants of outcome

    NARCIS (Netherlands)

    Z.S. Lalmahomed (Zarina)

    2017-01-01

    textabstractColorectal cancer (CRC) is one of the most common forms of cancer with annually, 1.36 million new patients and 694 000 deaths. The liver is the most common organ affected by metastatic disease. Disease staging is performed by the TNM classification system and therapeutic strategies are

  19. Lifestyle Changes and the Risk of Colorectal Cancer among ...

    African Journals Online (AJOL)

    Scientific observations have shown low prevalence of this cancer in sub-Saharan Africa, Middle East, South Asia and the Caribbean. This is not so for Australasia, North America and Western Europe where the prevalence of colorectal cancer is high. Evidence have shown that migrant populations from low risk regions to ...

  20. Validation of colorectal cancer surgery data from administrative data sources

    Directory of Open Access Journals (Sweden)

    Li Xue

    2012-07-01

    Full Text Available Abstract Background Surgery is the primary treatment for colorectal cancer for both curative and palliative intent. Availability of high quality surgery data is essential for assessing many aspects of the quality of colorectal cancer care. The objective of this study was to determine the quality of different administrative data sources in identifying surgery for colorectal cancer with respect to completeness and accuracy. Methods All residents in Alberta, Canada who were diagnosed with invasive colorectal cancer in years 2000-2005 were identified from the Alberta Cancer Registry and included in the study. Surgery data for these patients were obtained from the Cancer Registry (which collects the date of surgery for which the primary tumor was removed and compared to surgery data obtained from two different administrative data sources: Physician Billing and Hospital Inpatient data. Sensitivity, specificity, positive predictive value, negative predictive value and observed agreement were calculated compared to the Cancer Registry data. Results The Physician Billing data alone or combined with Hospital Inpatient data demonstrated equally high sensitivity (97% for both and observed agreement with the Cancer Registry data (93% for both for identifying surgeries. The Hospital Inpatient data, however, had the highest specificity (80%. The positive predictive value varied by disease stage and across data sources for stage IV (99% for stages I-III and 83-89% for stage IV, the specificity is better for colon cancer surgeries (72-85% than for rectal cancer surgeries (60-73%; validation measures did not vary over time. Conclusion Physician Billing data identify the colorectal cancer surgery more completely than Hospital Inpatient data although both sources have a high level of completeness.

  1. [Virtual colonoscopy in stenosing colorectal cancer].

    Science.gov (United States)

    Cirocchi, Roberto; Coccetta, Marco; Giuliani, Daniele; Morelli, Umberto; Spizzirri, Alessandro; Cattorini, Lorenzo; Mancioli, Francesco; Giustozzi, Gianmario; Sciannameo, Francesco

    2008-01-01

    In 5-10% of patients it is not possible to achieve a complete endoscopic examination of the colon, because of obstructing cancer, excessive length of the colon, anatomical abnormalities or adhesions. Virtual colonoscopy is currently capable of investigating the colic lumen with a non-invasive technique, with high specificity and sensitivity. From January 2005 to July 2007 we treated 21 patients with obstructing neoplastic colorectal lesions, preventing a complete endoscopic examination. In all patients we performed a virtual colonoscopy, which revealed the presence of synchronous lesions (19%): a pedunculated polyp in two cases, a sessile polyp in one case and a right colonic vegetating lesion. In the 21 patients studied we performed a follow-up colonoscopy 3 months after the surgical treatment. No other endoluminal lesions were found, confirming the results of virtual colonoscopy. In our experience virtual colonoscopy presented 100% sensitivity and specificity. In this selected group of patients with obstructing lesions of the colon, virtual colonoscopy enables the surgeon to evaluate the entire colon, avoiding the execution of an intraoperative colonoscopy and possible surgical reintervention due to the finding of synchronous neoplastic lesions at postoperative follow-up endoscopy.

  2. Factors Influencing Colorectal Cancer Screening Participation

    Directory of Open Access Journals (Sweden)

    Antonio Z. Gimeno García

    2012-01-01

    Full Text Available Colorectal cancer (CRC is a major health problem worldwide. Although population-based CRC screening is strongly recommended in average-risk population, compliance rates are still far from the desirable rates. High levels of screening uptake are necessary for the success of any screening program. Therefore, the investigation of factors influencing participation is crucial prior to design and launches a population-based organized screening campaign. Several studies have identified screening behaviour factors related to potential participants, providers, or health care system. These influencing factors can also be classified in non-modifiable (i.e., demographic factors, education, health insurance, or income and modifiable factors (i.e., knowledge about CRC and screening, patient and provider attitudes or structural barriers for screening. Modifiable determinants are of great interest as they are plausible targets for interventions. Interventions at different levels (patient, providers or health care system have been tested across the studies with different results. This paper analyzes factors related to CRC screening behaviour and potential interventions designed to improve screening uptake.

  3. Plant sterol intakes and colorectal cancer risk in the Netherlands : cohort study on diet and cancer

    NARCIS (Netherlands)

    Normén, A.L.; Brants, H.A.M.; Voorrips, L.E.; Andersson, H.A.; Brandt, P.A. van den

    2001-01-01

    Background: Plant sterols in vegetable foods might prevent colorectal cancer. Objective: The objective was to study plant sterol intakes in relation to colorectal cancer risk in an epidemiologic study. Design: The study was performed within the framework of the Netherlands Cohort Study on Diet and

  4. Quality-of-life assessment in colorectal cancer patients: evaluation of cancer therapies

    NARCIS (Netherlands)

    Sprangers, M. A.

    1999-01-01

    There is increasing recognition of the need to assess the impact of colorectal cancer and its treatment on patients' quality of life (QL). An overview is provided of generic and (colorectal) cancer-specific QL questionnaires that yield adequate levels of reliability and validity. These measures have

  5. Cancer risks for monoallelic MUTYH mutation carriers with a family history of colorectal cancer

    National Research Council Canada - National Science Library

    Win, Aung Ko; Cleary, Sean P; Dowty, James G; Baron, John A; Young, Joanne P; Buchanan, Daniel D; Southey, Melissa C; Burnett, Terrilea; Parfrey, Patrick S; Green, Roger C; Marchand, Loïc Le; Newcomb, Polly A; Haile, Robert W; Lindor, Noralane M; Hopper, John L; Gallinger, Steven; Jenkins, Mark A

    2011-01-01

    ...‐degree relatives of 144 incident colorectal cancer (CRC) cases who were monoallelic or biallelic mutation carriers ascertained by sampling population complete cancer registries in the United States, Canada and Australia...

  6. Diverticulosis and the risk of interval colorectal cancer.

    Science.gov (United States)

    Cooper, Gregory S; Xu, Fang; Schluchter, Mark D; Koroukian, Siran M; Barnholtz Sloan, Jill S

    2014-11-01

    Diverticulosis, a prevalent condition at screening colonoscopy, has been associated with colorectal cancers that develop after a clearing colonoscopy, or interval cancers. To quantify the overall risk of diverticulosis in the development of interval cancers and examine this association in relevant subgroups. Using a linked database containing SEER tumor registry data and Medicare claims, we identified patients aged ≥69 years with colorectal cancer who underwent colonoscopy within 6 months of diagnosis. Patients with an additional colonoscopy from 36 to 6 months prior to cancer diagnosis were characterized as having interval cancers. We compared characteristics of patients with interval cancers and detected cancers according to a diagnosis of diverticulosis not associated with a colonoscopy procedure from 1991 through the date of the most recent colonoscopy in both univariate and multivariate models. A previous diagnosis of diverticulosis was documented in 14,452 (26.9 %) patients with detected cancers compared to 2,905 (69.3 %) patients with interval cancers (p diverticulosis diagnoses were without complications such as hemorrhage or diverticulitis. Diverticulosis was strongly associated with interval colorectal cancers in all segments of the colon. Given its known predominance in the left colon, the findings argue against impaired visualization of lesions at colonoscopy as the only pathogenic factor.

  7. OVOL2, an Inhibitor of WNT Signaling, Reduces Invasive Activities of Human and Mouse Cancer Cells and Is Down-regulated in Human Colorectal Tumors.

    Science.gov (United States)

    Ye, Guo-Dong; Sun, Guang-Bin; Jiao, Peng; Chen, Chen; Liu, Qing-Feng; Huang, Xiao-Li; Zhang, Rui; Cai, Wang-Yu; Li, Sheng-Nan; Wu, Jia-Fa; Liu, Yun-Jia; Wu, Rong-Si; Xie, Yuan-Yuan; Chan, Err-Cheng; Liou, Yih-Cherng; Li, Bo-An

    2016-03-01

    -catenin, facilitating recruitment of histone deacetylase 1 to the TCF4-β-catenin complex; this inhibited expression of epithelial-to-mesenchymal transition-related genes regulated by WNT, such as SLUG, in CRC cell lines. OVOL2 was a downstream target of WNT signaling in LS174T and SW480 cells. The OVOL2 promoter was hypermethylated in late-stage CRC specimens from patients and in SW620 cells; hypermethylation resulted in OVOL2 down-regulation and an inability to inhibit WNT signaling. Disruption of Ovol2 in Apc(min/+) mice increased WNT activity in intestinal tissues and the formation of invasive intestinal tumors. OVOL2 is a colorectal tumor suppressor that blocks WNT signaling by facilitating the recruitment of histone deacetylase 1 to the TCF4-β-catenin complex. Strategies to increase levels of OVOL2 might be developed to reduce colorectal tumor progression and metastasis. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

  8. Heterogenous mismatch-repair status in colorectal cancer

    DEFF Research Database (Denmark)

    Joost, Patrick; Veurink, Nynke; Holck, Susanne

    2014-01-01

    BACKGROUND: Immunohistochemical staining for mismatch repair proteins is efficient and widely used to identify mismatch repair defective tumors. The tumors typically show uniform and widespread loss of MMR protein staining. We identified and characterized colorectal cancers with alternative......, heterogenous mismatch repair protein staining in order to delineate expression patterns and underlying mechanisms. METHODS: Heterogenous staining patterns that affected at least one of the mismatch repair proteins MLH1, PMS2, MSH2 and MSH6 were identified in 14 colorectal cancers. Based on alternative....... CONCLUSIONS: Heterogenous mismatch repair status can be demonstrated in colorectal cancer. Though rare, attention to this phenomenon is recommended since it corresponds to differences in mismatch repair status that are relevant for correct classification. VIRTUAL SLIDES: The virtual slide(s) for this article...

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

    Science.gov (United States)

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

    2015-03-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  11. Clinical Aspects of Hypoxia-inducible Factors in Colorectal Cancer

    DEFF Research Database (Denmark)

    Havelund, Birgitte Mayland; Spindler, Karen-Lise Garm; Sørensen, Flemming Brandt

    Clinical Aspects of Hypoxia-inducible Factors in Colorectal Cancer   Birgitte Mayland Havelund1,4 MD, Karen-Lise Garm Spindler1,4 MD, PhD, Flemming Brandt Sørensen2,4 MD, DMSc, Ivan Brandslund3 MD, DMSc, Anders Jakobsen1,4 MD, DMSc. 1Department of Oncology, 2Pathology and 3Biochemistry, Vejle...... Hospital, Vejle, Denmark 4Institute of Regional Health Services Research, University of Southern Denmark, Odense Denmark Background Prognostic and predictive markers are needed for individualizing the treatment of colorectal cancer. Hypoxia-inducible factor 1α (HIF-1α) is a transcription-inducing factor...... is to investigate the predictive and prognostic value of HIF-1α in colorectal cancer. Materials and Methods The project is divided into 3 substudies: 1. Biological and methodological aspects. The expression of HIF-1α measured by immunohistochemistry in paraffin embedded tissue is related to single nucleotide...

  12. Validity of data in the Danish Colorectal Cancer Screening Database

    DEFF Research Database (Denmark)

    Thomsen, Mette Kielsholm; Njor, Sisse Helle; Linnemann, Dorte

    2017-01-01

    Background: In Denmark, a nationwide screening program for colorectal cancer was implemented in March 2014. Along with this, a clinical database for program monitoring and research purposes was established. Objective: The aim of this study was to estimate the agreement and validity of diagnosis...... and procedure codes in the Danish Colorectal Cancer Screening Database (DCCSD). Methods: All individuals with a positive immunochemical fecal occult blood test (iFOBT) result who were invited to screening in the first 3 months since program initiation were identified. From these, a sample of 150 individuals...... of codes varied from moderate to high. Thus, the DCCSD may be a valuable data source for future research on colorectal cancer screening....

  13. Third-line therapy for metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Gundgaard, M.G.; Ehrnrooth, E.; Sørensen, Jens Benn

    2008-01-01

    , panitumumab. As a result, third-line treatment is now a necessary step in the optimal treatment of patients with metastatic colorectal cancer (MCRC). MATERIALS AND METHODS: We conducted a literature review of English language publications on third-line therapy for MCRC from January 2000 to April 2007. Data......BACKGROUND: The past years' therapy for colorectal cancer has evolved rapidly with the introduction of novel cytotoxic agents such as irinotecan, capecitabine and oxaliplatin. Further advances have been achieved with the integration of targeted agents such as bevacizumab, cetuximab and recently......OS of 16 months. With irinotecan and 5-FU, mOS around 8 months were reported and with cetuximab combined with irinotecan, the highest mOS was 9.8 months. CONCLUSION: Third-line therapy in advanced colorectal cancer may improve mOS for patients with MCRC. Therefore, randomized studies should be conducted...

  14. A real health problem of our days: Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Gheorghita Raluca-Andreea

    2016-02-01

    Full Text Available Colorectal cancer is one of the major mortality causes in the world, with an increased frequency in western countries, which are better developed economically. Romanian statistics show that the frequency of this type of cancer is increasing rapidly. In the year 2000, all over the world there were approximately 1 million new cases of colorectal cancer, and over 500 thousands deaths, thus affecting 1 from 20 inhabitants from the developed countries and being the second main cancer death cause, at both sexes in Europe. In Romania, incidence and mortality have doubled in the last 20 years, reaching a 17.74/100000 inhabitants incidence in the year 2000. Both for men and women, this disease is on the 3rd place in Romania, after bronhopulmonary cancer and gastric (for men and breast and uterus cancer, respectively.

  15. Risk Prediction Models for Colorectal Cancer: A Systematic Review.

    Science.gov (United States)

    Usher-Smith, Juliet A; Walter, Fiona M; Emery, Jon D; Win, Aung K; Griffin, Simon J

    2016-01-01

    Colorectal cancer is the second leading cause of cancer-related death in Europe and the United States. Survival is strongly related to stage at diagnosis and population-based screening reduces colorectal cancer incidence and mortality. Stratifying the population by risk offers the potential to improve the efficiency of screening. In this systematic review we searched Medline, EMBASE, and the Cochrane Library for primary research studies reporting or validating models to predict future risk of primary colorectal cancer for asymptomatic individuals. A total of 12,808 papers were identified from the literature search and nine through citation searching. Fifty-two risk models were included. Where reported (n = 37), half the models had acceptable-to-good discrimination (the area under the receiver operating characteristic curve, AUROC >0.7) in the derivation sample. Calibration was less commonly assessed (n = 21), but overall acceptable. In external validation studies, 10 models showed acceptable discrimination (AUROC 0.71-0.78). These include two with only three variables (age, gender, and BMI; age, gender, and family history of colorectal cancer). A small number of prediction models developed from case-control studies of genetic biomarkers also show some promise but require further external validation using population-based samples. Further research should focus on the feasibility and impact of incorporating such models into stratified screening programmes. ©2015 American Association for Cancer Research.

  16. Time dependent ethnic convergence in colorectal cancer survival in hawaii

    Directory of Open Access Journals (Sweden)

    Hundahl Scott A

    2003-02-01

    Full Text Available Abstract Background Although colorectal cancer death rates have been declining, this trend is not consistent across all ethnic groups. Biological, environmental, behavioral and socioeconomic explanations exist, but the reason for this discrepancy remains inconclusive. We examined the hypothesis that improved cancer screening across all ethnic groups will reduce ethnic differences in colorectal cancer survival. Methods Through the Hawaii Tumor Registry 16,424 patients diagnosed with colorectal cancer were identified during the years 1960–2000. Cox regression analyses were performed for each of three cohorts stratified by ethnicity (Caucasian, Japanese, Hawaiian, Filipino, and Chinese. The models included stage of diagnosis, year of diagnosis, age, and sex as predictors of survival. Results Mortality rates improved significantly for all ethnic groups. Moreover, with the exception of Hawaiians, rates for all ethnic groups converged over time. Persistently lower survival for Hawaiians appeared linked with more cancer treatment. Conclusion Ethnic disparities in colorectal cancer mortality rates appear primarily the result of differential utilization of health care. If modern screening procedures can be provided equally to all ethnic groups, ethnic outcome differences can be virtually eliminated.

  17. Colorectal cancer complicated by perforation. Specific features of surgical tactics

    Directory of Open Access Journals (Sweden)

    S. N. Shchaeva

    2015-01-01

    Full Text Available Objective: to assess the immediate results of surgical interventions for colorectal cancer complicated by perforation.Materials and methods. The immediate results of surgical treatment were retrospectively analyzed in 56 patients with colorectal cancer complicated by perforated colon cancer, who had been treated at Smolensk surgical hospitals in 2001 to 2013. Patients with diastatic perforation of the colon in the presence of decompensated obturation intestinal obstruction of tumor genesis were not included into this investigation.Results. The immediate results of uni- and multistage surgical interventions were analyzed in relation to the extent of peritonitis and the stage of colon cancer. More satisfactory immediate results were observed after multistage surgical treatment. Following these interventions, a fatal outcome of disseminated peritonitis in the presence of performed colorectal cancer was recorded in 8 (53.3 % cases whereas after symptomatic surgery there were 11 (67.8 % deaths. A fatal outcome was noted in 1 case (7.7 % after multistage surgery.Discussion. The results of surgical treatment in the patients with perforated colorectal cancer are directly related to the degree of peritonitis and the choice of surgical tactics.

  18. Have You Been Tested for Colorectal Cancer? PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2013-11-05

    This 60 second public service announcement is based on the November 2013 CDC Vital Signs report. Colorectal cancer screening saves lives, but only if you get tested. If you’re between 50 and 75, talk with your doctor about which test is best for you. If you have inflammatory bowel disease or a family history of colorectal cancer or polyps, ask your doctor if you should start screening before age 50.  Created: 11/5/2013 by Centers for Disease Control and Prevention (CDC).   Date Released: 11/5/2013.

  19. Mutator gene and hereditary non-polyposis colorectal cancer

    Science.gov (United States)

    de la Chapelle, Albert [Helsingfors, FI; Vogelstein, Bert [Baltimore, MD; Kinzler, Kenneth W [Baltimore, MD

    2008-02-05

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

  20. Cancer in numbers: Do preventive measures for colorectal cancer apply?

    Directory of Open Access Journals (Sweden)

    Pedro J. Tárraga López

    2017-10-01

    Full Text Available Abstract: Introduction: Cancer is a global problem as it will affect one in three men and one in four women during their lifetime. Colorectal cancer (CRC is the second most common cancer in men, after lung cancer, and is the second most common cancer in women after breast cancer. It is also the second leading cause of death in men and women separately, and is the second most common cause of cancer death if both genders are considered together. CRC accounts for approximately 10% of cancer deaths. Modifiable risk factors for CRC include smoking, physical inactivity, overweight and obesity, processed meat consumption, and excessive alcohol consumption. CRC screening programs are possible in economically developed countries. However, attention should be paid in the future to geographically populated areas and western lifestyles. Objective: To evaluate the effect on the incidence and mortality of diet and lifestyle of CRC and to determine the effect of secondary prevention through the early diagnosis of CRC. Methodology: An exhaustive search of Medline and Pubmed articles related to primary and secondary prevention of CRC is carried out and a meta-analysis of the same blocks is carried out. Results: 301 items related to primary or secondary prevention of CRC were recovered. Of these, 177 were considered valid in the meta-analysis: 12 in epidemiology, 56 in diet and lifestyle, and over 77 different projections for the early detection of CRC. Cancer is a global problem as it will affect one in three men and one in four women during their lifetime. There is no question of which environmental factors, probably diet, may explain these cancer rates. Excessive consumption of alcohol and high cholesterol diet are associated with a high risk of colon cancer. A diet low in folic acid and vitamin B6 is also associated with an increased risk of developing colon cancer with overexpression of p53. Eating pulses at least three times a week reduces the risk of

  1. Clinical and Biological Features of Interval Colorectal Cancer

    OpenAIRE

    Lee, Yu Mi; Huh, Kyu Chan

    2017-01-01

    Interval colorectal cancer (I-CRC) is defined as a CRC diagnosed within 60 months after a negative colonoscopy, taking into account that 5 years is the ?mean sojourn time.? It is important to prevent the development of interval cancer. The development of interval colon cancer is associated with female sex, old age, family history of CRC, comorbidities, diverticulosis, and the skill of the endoscopist. During carcinogenesis, sessile serrated adenomas/polyps (SSA/Ps) share many genomic and colo...

  2. Multifaceted nature of membrane microdomains in colorectal cancer

    OpenAIRE

    Jahn, Kristina A; Su, Yingying; Braet, Filip

    2011-01-01

    Membrane microdomains or lipid rafts are known to be highly dynamic and to act as selective signal transduction mediators that facilitate interactions between the cell’s external and internal environments. Lipid rafts play an important mediating role in the biology of cancer: they have been found in almost all existing experimental cancer models, including colorectal cancer (CRC), and play key regulatory roles in cell migration, metastasis, cell survival and tumor progression. This paper expl...

  3. Incidence of colorectal cancer in young patients.

    Science.gov (United States)

    Campos, Fábio Guilherme C M DE; Figueiredo, Marleny Novaes; Monteiro, Mariane; Nahas, Sérgio Carlos; Cecconello, Ivan

    2017-01-01

    Sporadic colorectal cancer (CRC) is traditionally diagnosed after de sixth decade of life, although a small percentage of cases are diagnosed in patients under 40 years of age, and incidence is increasing. There exists a great volume of controversy regarding clinical outcome of young patients diagnosed with colorectal cancer (CRC) when compared to elder counterparts. Our aims were to evaluate the rate of CRC in young patients, to review the pertaining literature and to discuss outcomes and clinical prognosis. A retrospective review involving patients with CRC was undertaken, focusing on age at diagnosis. The information extracted from this literature review showed a trend towards a decreased incidence in older people with an opposite effect among adolescents and young adults. Moreover, biological aggressiveness in young adults diagnosed with CRC has not been fully recognized, although it is usually diagnosed later and in association with adverse histological features. Besides that, these features don't affect outcome. These apparent increase in CRC incidence among young patients during the last decades raises the need for a greater suspicious when evaluating common symptoms in this group. Thus, educational programs should widespread information for both population and physicians to improve prevention and early diagnosis results. RESUMO O câncer colorretal (CCR) esporádico é tradicionalmente diagnosticado após a sexta década de vida, embora uma pequena porcentagem de casos seja diagnosticada em doentes abaixo dos 40 anos de idade, e a incidência está aumentando. Existe uma grande controvérsia a respeito da evolução clínica de doentes jovens portadores de CCR em comparação aos mais idosos. Os objetivos deste estudo foram avaliar a prevalência de CCR em doentes jovens, rever a literatura pertinente e discutir suas características mais importantes nesta faixa etária. Para tanto realizou-se revisão da literatura envolvendo doentes com CCR com foco na

  4. Microsatellite Status of Primary Colorectal Cancer Predicts the Incidence of Postoperative Colorectal Neoplasms.

    Science.gov (United States)

    Takiyama, Aki; Tanaka, Toshiaki; Yamamoto, Yoko; Hata, Keisuke; Ishihara, Soichiro; Nozawa, Hiroaki; Kawai, Kazushige; Kiyomatsu, Tomomichi; Nishikawa, Takeshi; Otani, Kensuke; Sasaki, Kazuhito; Watanabe, Toshiaki

    2017-10-01

    Few studies have evaluated the risk of postoperative colorectal neoplasms stratified by the nature of primary colorectal cancer (CRC). In this study, we revealed it on the basis of the microsatellite (MS) status of primary CRC. We retrospectively reviewed 338 patients with CRC and calculated the risk of neoplasms during postoperative surveillance colonoscopy in association with the MS status of primary CRC. A propensity score method was applied. We identified a higher incidence of metachronous rectal neoplasms after the resection of MS stable CRC than MS instable CRC (adjusted HR 5.74, p=0.04). We also observed a higher incidence of colorectal tubular adenoma in patients with MSS CRC (adjusted hazard ratio 7.09, pneoplasms. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  5. Moderate Alcohol Consumption and Colorectal Cancer Risk.

    Science.gov (United States)

    Klarich, DawnKylee S; Brasser, Susan M; Hong, Mee Young

    2015-08-01

    Heavy alcohol drinking is a risk factor for colorectal cancer (CRC); previous studies have shown a linear dose-dependent association between alcohol intake and CRC. However, some studies suggest that moderate alcohol consumption may have a protective effect, similar to that seen in cardiovascular disease. Other factors may interact with alcohol and contribute additional risk for CRC. We aimed to determine the association between moderate alcohol consumption, limited to 30 g of alcohol per day, by beverage type on CRC risk and to assess the effects of other factors that interact with alcohol to influence CRC risk. The PubMed database was used to find articles published between 2008 and 2014 related to alcohol and CRC. Twenty-one relevant articles were evaluated and summarized, including 11 articles reporting on CRC risk associated with moderate intake and 10 articles focusing on genetic interactions associated with alcohol and CRC risk. The association between alcohol and increased risk for CRC was found when intakes exceeded 30 g/d alcohol. Nonsignificant results were consistently reported for intakes alcohol consumers. Some significant results suggest that the development of CRC is dependent on the interaction of gene and environment. The association between the amount of alcohol consumed and the incidence of CRC was not significant at moderate intake levels. Moderate alcohol consumption was associated with a reduced CRC risk in study populations with greater adherence to a Mediterranean diet, where wine contributed substantially to the alcoholic beverage consumed. Other factors such as obesity, folate deficiency, and genetic susceptibility may contribute additional CRC risk for those consuming alcohol. To minimize CRC risk, appropriate recommendations should encourage intakes below 30 g of alcohol each day. Copyright © 2015 by the Research Society on Alcoholism.

  6. Second primary colorectal cancer in the era of prevalent screening and imaging.

    Science.gov (United States)

    Bae, Susie; Asadi, Muslim; Jones, Ian; McLaughlin, Stephen; Bui, Andrew; Steele, Malcolm; Tie, Jeanne; Gibbs, Peter

    2013-12-01

    Oncology literature is increasingly recognizing prevalence of second primary cancers including several longitudinal studies showing an increased risk of colorectal cancer following a prostate cancer diagnosis. A retrospective study was conducted to examine the relationship between prior prostate cancer diagnoses and subsequent colorectal cancer diagnoses. A multi-centre prospective colorectal cancer registry was queried for patients with a prior history of prostate, breast or lung cancer. Characteristics of these patients were compared to patients with colorectal cancer and no prior cancer history. Of 4660 cases of colorectal cancer diagnosed between 1998 and 2011, 2665 (57.2%) were male, median age was 68 years. For patients with a history of prostate cancer (n = 111), breast cancer (n = 61) and lung cancer (n = 23), the great majority of subsequent colorectal cancer diagnoses occurred in the initial 2 to 4 years after the first cancer diagnosis. This was accompanied by an increased rate of asymptomatic colorectal cancer at presentation, due to both screen detected and incidental cancer diagnoses. There was no clear relationship between any prostate cancer treatment and subsequent colorectal cancer risk, location or timing. In the modern era, there is an increased rate of colorectal cancer diagnosis in years shortly following another common cancer history. This is consistently seen across different primary tumour streams including prostate, breast and lung cancers and in part contributed by screen detected and incidental colorectal cancer diagnoses. Future studies should consider this potential confounding factor when asserting an increased rate of colorectal cancer as a second primary cancer. © 2013 The Authors. ANZ Journal of Surgery © 2013 Royal Australasian College of Surgeons.

  7. Active smoking and mortality among colorectal cancer survivors: the Cancer Prevention Study II nutrition cohort.

    Science.gov (United States)

    Yang, Baiyu; Jacobs, Eric J; Gapstur, Susan M; Stevens, Victoria; Campbell, Peter T

    2015-03-10

    Active smoking is associated with higher colorectal cancer risk, but its association with survival after colorectal cancer diagnosis is unclear. We investigated associations of smoking, before and after diagnosis, with all-cause and colorectal cancer-specific mortality among colorectal cancer survivors. From a cohort of adults who were initially free of colorectal cancer, we identified 2,548 persons diagnosed with invasive, nonmetastatic colorectal cancer between baseline (1992 or 1993) and 2009. Vital status and cause of death were determined through 2010. Smoking was self-reported on the baseline questionnaire and updated in 1997 and every 2 years thereafter. Postdiagnosis smoking information was available for 2,256 persons (88.5%). Among the 2,548 colorectal cancer survivors, 1,074 died during follow-up, including 453 as a result of colorectal cancer. In multivariable-adjusted Cox proportional hazards regression models, prediagnosis current smoking was associated with higher all-cause mortality (relative risk [RR], 2.12; 95% CI, 1.65 to 2.74) and colorectal cancer-specific mortality (RR, 2.14; 95% CI, 1.50 to 3.07), whereas former smoking was associated with higher all-cause mortality (RR, 1.18; 95% CI, 1.02 to 1.36) but not with colorectal cancer-specific mortality (RR, 0.89; 95% CI, 0.72 to 1.10). Postdiagnosis current smoking was associated with higher all-cause (RR, 2.22; 95% CI, 1.58 to 3.13) and colorectal cancer-specific mortality (RR, 1.92; 95% CI, 1.15 to 3.21), whereas former smoking was associated with all-cause mortality (RR, 1.21; 95% CI, 1.03 to 1.42). This study adds to the existing evidence that cigarette smoking is associated with higher all-cause and colorectal cancer-specific mortality among persons with nonmetastatic colorectal cancer. © 2015 by American Society of Clinical Oncology.

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

    Science.gov (United States)

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

    2009-11-01

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

  9. Prevalence and Risk Factors of Gastric Adenoma and Gastric Cancer in Colorectal Cancer Patients

    Directory of Open Access Journals (Sweden)

    Dae Hyun Tak

    2016-01-01

    Full Text Available Background/Aims. To evaluate the incidence of gastric adenoma and gastric cancer in colorectal cancer patients, as well as the clinicopathological features that affect their incidence. Methods. Among patients who underwent surgery after being diagnosed with colorectal cancer between January 2004 and December 2013 at Chungnam National University Hospital, 142 patients who underwent follow-up upper gastrointestinal endoscopy were assigned to the patient group. The control group included 426 subjects randomly selected. The patient group was subdivided into two: one that developed gastric adenoma or cancer and one that did not. Clinicopathological characteristics were compared between these groups. Results. In total, 35 (24.6% colorectal cancer patients developed a gastric adenoma or gastric cancer, which was higher than the number in the control group (20 [4.7%] patients; p<0.001. Age, alcohol history, and differentiation of colorectal cancer were associated with higher risks of gastric adenoma or gastric cancer, with odds ratios of 1.062, 6.506, and 5.901, respectively. Conclusions. In colorectal cancer patients, screening with upper gastrointestinal endoscopy is important, even if no lesions are noted in the upper gastrointestinal tract at colorectal cancer diagnosis. Endoscopic screening is particularly important with increasing age, history of alcohol consumption, and poor cancer differentiation.

  10. Ubiquitin-specific peptidase 22 inhibits colon cancer cell invasion by suppressing the signal transducer and activator of transcription 3/matrix metalloproteinase 9 pathway.

    Science.gov (United States)

    Ao, Ning; Liu, Yanyan; Bian, Xiaocui; Feng, Hailiang; Liu, Yuqin

    2015-08-01

    Colon cancer is associated with increased cell migration and invasion. In the present study, the role of ubiquitin-specific peptidase 22 (USP22) in signal transducer and activator of transcription 3 (STAT3)-mediated colon cancer cell invasion was investigated. The messenger RNA levels of STAT3 target genes were measured by reverse transcription-quantitative polymerase chain reaction, following USP22 knockdown by RNA interference in SW480 colon cancer cells. The matrix metalloproteinase 9 (MMP9) proteolytic activity and invasion potential of SW480 cells were measured by zymography and Transwell assay, respectively, following combined USP22 and STAT3 short interfering (si)RNA treatment or STAT3 siRNA treatment alone. Similarly, a cell counting kit-8 assay was used to detect the proliferation potential of SW480 cells. The protein expression levels of USP22, STAT3 and MMP9 were detected by immunohistochemistry in colon cancer tissue microarrays (TMAs) and the correlation between USP22, STAT3 and MMP9 was analyzed. USP22/STAT3 co-depletion partly rescued the MMP9 proteolytic activity and invasion of SW480 cells, compared with that of STAT3 depletion alone. However, the proliferation of USP22/STAT3si-SW480 cells was decreased compared with that of STAT3si-SW480 cells. USP22 expression was positively correlated with STAT3 and MMP9 expression in colon cancer TMAs. In conclusion, USP22 attenuated the invasion capacity of colon cancer cells by inhibiting the STAT3/MMP9 signaling pathway.

  11. Serrated polyps - a concealed but prevalent precursor of colorectal cancer.

    Science.gov (United States)

    Thorlacius, Henrik; Takeuchi, Yoji; Kanesaka, Takashi; Ljungberg, Otto; Uedo, Noriya; Toth, Ervin

    Serrated polyps have long been considered to lack malignant potential but accumulating data suggest that these lesions may cause up to one-third of all sporadic colorectal cancer. Serrated polyps are classified into three subtypes, including sessile serrated adenomas/polyps (SSA/Ps), traditional serrated adenomas (TSAs), and hyperplastic polyps (HPs). SSA/P and TSA harbour malignant potential but TSA represents only 1-2%, wheras SSA/P constitute up to 20% of all serrated lesions. HPs are most common (80%) of all serrated polyps but are considered to have a low potential of developing colorectal cancer. Due to their subtle appearence, detection and removal of serrated polyps pose a major challenge to endoscopists. Considering that precancerous serrated polyps are predominately located in the right colon could explain why interval cancers most frequently appear in the proximal colon and why colonoscopy is less protective against colon cancer in the proximal compared to the distal colon. Despite the significant impact on colorectal cancer incidence, the aetiology, incidence, prevalence, and natural history of serrated polyps is incompletely known. To effectively detect, remove, and follow-up serrated polyps, endoscopists and pathologists should be well-informed about serrated polyps. This review highlights colorectal serrated polyps in terms of biology, types, diagnosis, therapy, and follow-up.

  12. [Cost-effectiveness analysis on colorectal cancer screening program].

    Science.gov (United States)

    Huang, Q C; Ye, D; Jiang, X Y; Li, Q L; Yao, K Y; Wang, J B; Jin, M J; Chen, K

    2017-01-10

    Objective: To evaluate the cost-effectiveness of colorectal cancer screening program in different age groups from the view of health economics. Methods: The screening compliance rates, detection rates in different age groups were calculated by using the data from colorectal cancer screening program in Jiashan county, Zhejiang province. The differences in indicator among age groups were analyzed with χ(2) test or trend χ(2) test. The ratios of cost to the number of case were calculated according to cost statistics. Results: The detection rates of immunochemical fecal occult blood test (iFOBT) positivity, advanced adenoma and colorectal cancer and early stage cancer increased with age, while the early diagnosis rates were negatively associated with age. After exclusion the younger counterpart, the cost-effectiveness of individuals aged >50 years could be reduced by 15%-30%. Conclusion: From health economic perspective, it is beneficial to start colorectal cancer screening at age of 50 years to improve the efficiency of the screening.

  13. SLC25A22 Promotes Proliferation and Survival of Colorectal Cancer Cells With KRAS Mutations and Xenograft Tumor Progression in Mice via Intracellular Synthesis of Aspartate.

    Science.gov (United States)

    Wong, Chi Chun; Qian, Yun; Li, Xiaona; Xu, Jiaying; Kang, Wei; Tong, Joanna H; To, Ka-Fai; Jin, Ye; Li, Weilin; Chen, Huarong; Go, Minnie Y Y; Wu, Jian-Lin; Cheng, Ka Wing; Ng, Simon S M; Sung, Joseph J Y; Cai, Zongwei; Yu, Jun

    2016-11-01

    Many colorectal cancer (CRC) cells contain mutations in KRAS. Analyses of CRC cells with mutations in APC or CTNNB1 and KRAS identified SLC25A22, which encodes mitochondrial glutamate transporter, as a synthetic lethal gene. We investigated the functions of SLC25A22 in CRC cells with mutations in KRAS. We measured levels of SLC25A22 messenger RNA and protein in paired tumor and nontumor colon tissues collected from 130 patients in Hong Kong and 17 patients in China and compared protein levels with patient survival times. Expression of SLC25A22 was knocked down in KRAS mutant CRC cell lines (DLD1, HCT116, LOVO, SW480, SW620, and SW1116) and CRC cell lines without mutations in KRAS (CACO-2, COLO205, HT29, and SW48); cells were analyzed for colony formation, proliferation, glutaminolysis and aspartate synthesis, and apoptosis in Matrigel and polymerase chain reaction array analyses. DLD1 and HCT116 cells with SLC25A22 knockdown were grown as xenograft tumors in nude mice; tumor growth and metastasis were measured. SLC25A22 was expressed ectopically in HCT116 cells, which were analyzed in vitro and grown as xenograft tumors in nude mice. Levels of SLC25A22 messenger RNA and protein were increased in colorectal tumor tissues compared with matched nontumor colon tissues; increased protein levels were associated with shorter survival times of patients (P = .01). Knockdown of SLC25A22 in KRAS mutant CRC cells reduced their proliferation, migration, and invasion in vitro, and tumor formation and metastasis in mice, compared with cells without SLC25A22 knockdown. Knockdown of SLC25A22 reduced aspartate biosynthesis, leading to apoptosis, decreased cell proliferation in KRAS mutant CRC cells. Incubation of KRAS mutant CRC cells with knockdown of SLC25A22 with aspartate increased proliferation and reduced apoptosis, which required GOT1, indicating that oxaloacetate is required for cell survival. Decreased levels of oxaloacetate in cells with knockdown of SLC25A22 reduced

  14. Colorectal cancer screening and subsequent incidence of colorectal cancer: results from the 45 and Up Study.

    Science.gov (United States)

    Steffen, Annika; Weber, Marianne F; Roder, David M; Banks, Emily

    2014-11-03

    To investigate the association of colorectal cancer (CRC) screening history and subsequent incidence of CRC in New South Wales, Australia. A total of 196,464 people from NSW recruited to the 45 and Up Study, a large Australian population-based prospective study, by completing a baseline questionnaire distributed from January 2006 to December 2008. Individuals without pre-existing cancer were followed for a mean of 3.78 years (SD, 0.92 years) through linkage to population health datasets. Incidence of CRC; hazard ratio (HR) according to screening history, adjusted for age, sex, body mass index, income, education, remoteness, family history, aspirin use, smoking, diabetes, alcohol use, physical activity and dietary factors. Overall, 1096 cases of incident CRC accrued (454 proximal colon, 240 distal colon, 349 rectal and 53 unspecified cancers). Ever having undergone CRC screening before baseline was associated with a 44% reduced risk of developing CRC during follow-up (HR, 0.56; 95% CI, 0.49-0.63) compared with never having undergone screening. This effect was more pronounced for those reporting endoscopy (HR, 0.50; 95% CI, 0.43-0.58) than those reporting faecal occult blood testing (FOBT) (HR, 0.61; 95% CI, 0.52-0.72). Associations for all screening exposures were strongest for rectal cancer (HR, 0.35; 95% CI, 0.27-0.45) followed by distal colon cancer (HR, 0.60; 95% CI, 0.46-0.78), while relationships were weaker for cancers of the proximal colon (HR, 0.76; 95% CI, 0.62-0.92). CRC incidence is lower among individuals with a history of CRC screening, through either FOBT or endoscopy, compared with individuals who have never had CRC screening, lasting for at least 4 years after screening.

  15. Specific genomic aberrations in primary colorectal cancer are associated with liver metastases

    NARCIS (Netherlands)

    Bruin, S.C.; Klijn, C.N.; Liefers, G.J.; Braaf, L.M.; Joosse, S.A.; Van Beers, E.H.; Verwaal, V.J.; Morreau, H.; Wessels, L.F.; Van Velthuysen, M.L.F.; Tollenaar, R.A.E.M.; Van 't Veer, L.J.

    2010-01-01

    Background: Accurate staging of colorectal cancer (CRC) with clinicopathological parameters is important for predicting prognosis and guiding treatment but provides no information about organ site of metastases. Patterns of genomic aberrations in primary colorectal tumors may reveal a chromosomal

  16. Colorectal-Cancer Incidence and Mortality with Screening Flexible Sigmoidoscopy

    Science.gov (United States)

    Schoen, Robert E.; Pinsky, Paul F.; Weissfeld, Joel L.; Yokochi, Lance A.; Church, Timothy; Laiyemo, Adeyinka O.; Bresalier, Robert; Andriole, Gerald L.; Buys, Saundra S.; Crawford, E. David; Fouad, Mona N.; Isaacs, Claudine; Johnson, Christine C.; Reding, Douglas J.; O'Brien, Barbara; Carrick, Danielle M.; Wright, Patrick; Riley, Thomas L.; Purdue, Mark P.; Izmirlian, Grant; Kramer, Barnett S.; Miller, Anthony B.; Gohagan, John K.; Prorok, Philip C.; Berg, Christine D.

    2013-01-01

    Background The benefits of endoscopic testing for colorectal-cancer screening are uncertain. We evaluated the effect of screening with flexible sigmoidoscopy on colorectal-cancer incidence and mortality. Methods From 1993 through 2001, we randomly assigned 154,900 men and women 55 to 74 years of age either to screening with flexible sigmoidoscopy, with a repeat screening at 3 or 5 years, or to usual care. Cases of colorectal cancer and deaths from the disease were ascertained. Results Of the 77,445 participants randomly assigned to screening (intervention group), 83.5% underwent baseline flexible sigmoidoscopy and 54.0% were screened at 3 or 5 years. The incidence of colorectal cancer after a median follow-up of 11.9 years was 11.9 cases per 10,000 person-years in the intervention group (1012 cases), as compared with 15.2 cases per 10,000 person-years in the usual-care group (1287 cases), which represents a 21% reduction (relative risk, 0.79; 95% confidence interval [CI], 0.72 to 0.85; Pcolorectal cancer (479 cases in the intervention group vs. 669 cases in the usual-care group; relative risk, 0.71; 95% CI, 0.64 to 0.80; Pcolorectal cancer (512 cases vs. 595 cases; relative risk, 0.86; 95% CI, 0.76 to 0.97; P = 0.01). There were 2.9 deaths from colorectal cancer per 10,000 person-years in the intervention group (252 deaths), as compared with 3.9 per 10,000 person-years in the usual-care group (341 deaths), which represents a 26% reduction (relative risk, 0.74; 95% CI, 0.63 to 0.87; Pcolorectal cancer was reduced by 50% (87 deaths in the intervention group vs. 175 in the usual-care group; relative risk, 0.50; 95% CI, 0.38 to 0.64; Pcolorectal cancer was unaffected (143 and 147 deaths, respectively; relative risk, 0.97; 95% CI, 0.77 to 1.22; P = 0.81). Conclusions Screening with flexible sigmoidoscopy was associated with a significant decrease in colorectal-cancer incidence (in both the distal and proximal colon) and mortality (distal colon only). (Funded by the

  17. Activating mutation in MET oncogene in familial colorectal cancer

    Directory of Open Access Journals (Sweden)

    Schildkraut Joellen M

    2011-10-01

    Full Text Available Abstract Background In developed countries, the lifetime risk of developing colorectal cancer (CRC is 5%, and it is the second leading cause of death from cancer. The presence of family history is a well established risk factor with 25-35% of CRCs attributable to inherited and/or familial factors. The highly penetrant inherited colon cancer syndromes account for approximately 5%, leaving greater than 20% without clear genetic definition. Familial colorectal cancer has been linked to chromosome 7q31 by multiple affected relative pair studies. The MET proto-oncogene which resides in this chromosomal region is considered a candidate for genetic susceptibility. Methods MET exons were amplified by PCR from germline DNA of 148 affected sibling pairs with colorectal cancer. Amplicons with altered sequence were detected with high-resolution melt-curve analysis using a LightScanner (Idaho Technologies. Samples demonstrating alternative melt curves were sequenced. A TaqMan assay for the specific c.2975C >T change was used to confirm this mutation in a cohort of 299 colorectal cancer cases and to look for allelic amplification in tumors. Results Here we report a germline non-synonymous change in the MET proto-oncogene at amino acid position T992I (also reported as MET p.T1010I in 5.2% of a cohort of sibling pairs affected with CRC. This genetic variant was then confirmed in a second cohort of individuals diagnosed with CRC and having a first degree relative with CRC at prevalence of 4.1%. This mutation has been reported in cancer cells of multiple origins, including 2.5% of colon cancers, and in Conclusions Although the MET p.T992I genetic mutation is commonly found in somatic colorectal cancer tissues, this is the first report also implicating this MET genetic mutation as a germline inherited risk factor for familial colorectal cancer. Future studies on the cancer risks associated with this mutation and the prevalence in different at-risk populations will

  18. MTHFR polymorphisms as prognostic factors in sporadic colorectal cancer.

    Science.gov (United States)

    Osian, Gelu; Procopciuc, Lucia; Vlad, Liviu

    2007-09-01

    Theoretically, individuals having at least one mutant allele present a modified activity of the MTHFR enzyme and low methylation, DNA synthesis-repair respectively, which could imply a higher risk of colorectal cancer. The purpose of this study was to investigate the relations of these mutations with the clinico-pathological aspects of colorectal cancer. The study included 69 patients with sporadic colorectal cancer. The relative risk in homozygous patients with a normal allele and for mutations C667T and A1298C, in heterozygous patients with one normal and one mutant allele, and for homozygous patients for the mutant allele was calculated. C667T and A1298C mutations represent a risk factor for colorectal cancer with an OR (odds ratio) = 2.13 (CI (0.51-8.91)) and 3 (CI(0.3-29.58), respectively, in homozygous patients. These mutations are associated with a more frequent location of lesions at the colon level, OR=2.3 and 2.15 respectively. The incidence of the A1298C mutation was more frequent in stage N0 than N+ (p<0.05), pT2 vs. pT3 (p<0.05), as well as in Dukes stages B and D vs. A or C (p<0.05). The results obtained support the hypothesis of an increased colorectal cancer prevalence in patients with one of the MTHFR gene mutations. These patients develop colon cancer more frequently, they present lymph node invasion more rarely, and develop more often distant metastases.

  19. Breast and cervical cancer screening behaviours among colorectal cancer survivors in Nova Scotia

    Science.gov (United States)

    Corkum, M.; Urquhart, R.; Kephart, G.; Hayden, J.A.; Porter, G.

    2014-01-01

    Purpose We analyzed patterns and factors associated with receipt of breast and cervical cancer screening in a cohort of colorectal cancer survivors. Methods Individuals diagnosed with colorectal cancer in Nova Scotia between January 2001 and December 2005 were eligible for inclusion. Receipt of breast and cervical cancer screening was determined using administrative data. General-population age restrictions were used in the analysis (breast: 40–69 years; cervical: 21–75 years). Kaplan–Meier and Cox proportional hazards models were used to assess time to first screen. Results Of 318 and 443 colorectal cancer survivors eligible for the breast and cervical cancer screening analysis respectively, 30.1% [95% confidence interval (ci): 21.2% to 39.0%] never received screening mammography, and 47.9% (95% ci: 37.8% to 58.0%) never received cervical cancer screening during the study period. Receipt of screening before the colorectal cancer diagnosis was strongly associated with receipt of screening after diagnosis (hazard ratio for breast cancer screening: 4.71; 95% ci: 3.42 to 6.51; hazard ratio for cervical cancer screening: 6.83; 95% ci: 4.58 to 10.16). Conclusions Many colorectal cancer survivors within general-population screening age recommendations did not receive breast and cervical cancer screening. Future research should focus on survivors who meet age recommendations for population-based cancer screening. PMID:25302037

  20. Colorectal cancer in patients from Uganda: A histopathological study ...

    African Journals Online (AJOL)

    DN Dijxhoorn, A Boutall, CJ Mulder, R Ssebuufu, A Mall, S Kalungi, C Baigrie, PA Goldberg. Abstract. No Abstract. Keywords: Colorectal cancer, HNPCC, Endoscopy, Uganda, Histopathology, Lynch syndrome. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT.

  1. Use Of Chinese Medicine Among Colorectal Cancer Patients: A ...

    African Journals Online (AJOL)

    Materials and methods: A retrospective study was conducted using registration and claims data sets for 2007 from the National Health Insurance Research Database. Patients with colorectal cancer were identified from the Registry for Catastrophic illness Patients. Binary logistic regression was used to estimate odds ratios ...

  2. Message from Terrence Howard: Screening for Colorectal Cancer PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2010-04-13

    A message from the actor/musician Terrence Howard about the importance of screening for colorectal cancer.  Created: 4/13/2010 by Centers for Disease Control and Prevention (CDC).   Date Released: 4/13/2010.

  3. Message from Terrence Howard: Screening for Colorectal Cancer PSA (:20)

    Centers for Disease Control (CDC) Podcasts

    2010-04-13

    A message from the actor/musician Terrence Howard about the importance of screening for colorectal cancer.  Created: 4/13/2010 by Centers for Disease Control and Prevention (CDC).   Date Released: 4/13/2010.

  4. Prognosis and Survival in patients with Colorectal Cancer

    NARCIS (Netherlands)

    van Schaik, P.M.

    2012-01-01

    The aim of this thesis was to investigate the outcome after colorectal surgery and to try to find possible ways to improve staging and treatment, especially in patients with stage I and II colonic cancer. The first part of this thesis describes the outcome and quality of life in patients with

  5. Health Effects and Costs of Colorectal Cancer Screening

    NARCIS (Netherlands)

    J.A. Wilschut (Janneke)

    2012-01-01

    textabstractColorectal cancer (CRC) is a major public health problem, with over a million newly diagnosed cases per year worldwide. CRC occurs especially frequently in established market economies like Europe, the United States (US), Canada, Australia and Japan. The lifetime incidence in average

  6. Prognostic and predictive biomarkers in colorectal cancer. Towards precision medicine

    NARCIS (Netherlands)

    Reimers, Marlies Suzanne

    2015-01-01

    The aim of this thesis was to define prognostic and predictive biomarkers in colorectal cancer for improved risk stratification and treatment benefit in the individual patient, with the introduction of precision medicine in the near future as the ultimate goal. By definition, precision medicine is

  7. Pattern & presentation of colorectal cancer in central Sudan, a ...

    African Journals Online (AJOL)

    Beaumount hospital, Ireland, Surgery. 2. Gezira University, Faculty of Medicine, Surgery. 3. Ministry of Health. Abstract. Aims & objective: To determine the age and gender distribution and clinical presentation of patients together with histo- logical types of colorectal cancer cases presented to Ibn Sina specialized hospital.

  8. Oral microbiome and history of smoking and colorectal cancer.

    Science.gov (United States)

    Kato, Ikuko; Vasquez, Adrian A; Moyerbrailean, Gregory; Land, Susan; Sun, Jun; Lin, Ho-Sheng; Ram, Jeffrey L

    2016-10-01

    The equilibrium of oral microbiome may be altered by environmental factors, including cigarette smoking. Several recent studies also suggest that oral pathogens causing periodontal disease, such as Fusobacterium nucleatum, are involved in pathogenesis of colorectal cancer. For this study oral rinse DNA samples from 190 participants in a population-based case-control study for colorectal cancer were used to amplify a V3-V4 region of bacterial 16S rRNA gene. The amplicons were sequenced using Illumina MiSeq paired end chemistry on two runs, yielding approximately 35 million filtered reads which were assigned to bacterial phyla. No association was found between Fusobacterium abundance or presence and colorectal cancer. However, adjusted for age and experimental batch, colorectal cancer history was associated with increased presence of genus Lactobacillus and increased relative abundance of Rothia by 28% and current smoking was associated with a 33% decrease in relative counts of Betaproteobacteria (primarily Neisseria) and 23% increase in relative abundance of Veillonellaceae family. We also found that smoking had significant effects on the 2nd component scores and 2nd coordinate distances in principal component and coordinate analyses. It remains to be elucidated whether the observed differences can be translated into biochemical changes in oral environment, thus potentially affecting oral health.

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

    Science.gov (United States)

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

    2012-01-01

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

  10. [Colorectal cancer in senior patients - are we doing it well?

    Science.gov (United States)

    Kostrouch, D; Martínek, L; Hoch, J

    2017-01-01

    Geriatric patients form a significant part of patients with colorectal cancer and their numbers will probably continue to increase. Analysis of the quality of care provided to seniors and the results from their treatment are currently gaining more attention. The aim of this study was to compare how often standard oncological therapy is administered to seniors with colorectal cancer and to compare their results with younger patients along with complications of the therapy. A retrospective analysis of data from 170 patients with the diagnosis of colorectal cancer undergoing an elective curative surgical procedure in 2014 and 2015 was performed. Patients were divided into three groups according to their age (oncological treatment in the individual age groups. Patients 80 years and older had significantly higher ASA scores (p=0.0001) and significantly higher stages of tumors according to TNM-7 classification (p=0.0413) in comparison to younger patients. Differences in numbers of serious complications (oncological treatment (oncological treatment is possible even in selected patients that are 80 years and older. Implementation of more reliable methods to objectively predict postoperative complications can become a tool to modify the treatment and improve the results of surgical care in elderly patients.Key words: geriatric patients - oncosurgery complex geriatric assessment colorectal cancer.

  11. Visualising and quantifying angiogenesis in metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Hansen, Torben Frøstrup; Nielsen, Boye Schnack; Jakobsen, Anders

    2013-01-01

    Angiogenesis plays an important role in tumour growth and dissemination. We have recently shown that blood vessel density, determined by image analysis based on microRNA-126 (miRNA-126) in situ hybridization (ISH) in the primary tumours of metastatic colorectal cancers (mCRC), is predictive...

  12. Neoexpression of a functional primary cilium in colorectal cancer cells

    Directory of Open Access Journals (Sweden)

    Blanche Sénicourt

    2016-05-01

    Full Text Available The Hedgehog (HH signaling pathway is involved in the maintenance of numerous cell types both during development and in the adult. Often deregulated in cancers, its involvement in colorectal cancer has come into view during the last few years, although its role remains poorly defined. In most tissues, the HH pathway is highly connected to the primary cilium (PC, an organelle that recruits functional components and regulates the HH pathway. However, normal epithelial cells of the colon display an inactive HH pathway and lack a PC. In this study, we report the presence of the PC in adenocarcinoma cells of primary colorectal tumors at all stages. Using human colorectal cancer cell lines we found a clear correlation between the presence of the PC and the expression of the final HH effector, GLI1, and provide evidence of a functional link between the two by demonstrating the recruitment of the SMO receptor to the membrane of the primary cilium. We conclude that the primary cilium directly participates in the HH pathway in colorectal cancer cells.

  13. Role of chance in familial aggregaton of colorectal cancer

    DEFF Research Database (Denmark)

    Katballe, N.; Bentzen, S.M.; Christensen, M.

    2001-01-01

    A prospective population-based study recorded family trees of 77 colorectal cancer patients younger than 50 years of age. Using mathematical modeling of population age-incidence data, we estimate that 1 (95% confidence limits 0 and 3) of these families is expected to meet the Amsterdam criteria I...

  14. Presentation of Colorectal Cancer in Khartoum Teaching Hospital ...

    African Journals Online (AJOL)

    Aims: To determine the age and gender distribution in Sudanese patients with colorectal cancer, as seen in Khartoum Teaching Hospital, and to study its emergency presentation. Patients and Methods: This retrospective study was conducted in Khartoum Teaching Hospital (Sudan). Two hundred and seventy seven (277) ...

  15. Colorectal cancer during pregnancy in a Sudanese female | Idris ...

    African Journals Online (AJOL)

    We report a new case of uncommon but not rare condition of colorectal cancer during pregnancy in 33 years old Sudanese female at her 16th weeks of gestation presented with bloody diarrhea and intermittent left side abdominal pain. Initially she was diagnosed as a case of dysentery which was treated by antibiotics.

  16. Saliva and plasma TIMP-1 in patients with colorectal cancer

    DEFF Research Database (Denmark)

    Holten-Andersen, Lars; Christensen, Ib Jarle; Jensen, Siri Beier

    2012-01-01

    Background and aims. A prospective cross-sectional study was designed to test if total levels of TIMP-1 in saliva and plasma correlated with the diagnosis of colorectal cancer (CRC) in a population with symptoms consistent with this disease. Materials and methods. Stimulated whole saliva and bloo...

  17. [Laparoscopic versus open surgery for colorectal cancer. A comparative study].

    Science.gov (United States)

    Arribas-Martin, Antonio; Díaz-Pizarro-Graf, José Ignacio; Muñoz-Hinojosa, Jorge Demetrio; Valdés-Castañeda, Alberto; Cruz-Ramírez, Omar; Bertrand, Martin Marie

    2014-01-01

    Laparoscopic surgery for colorectal cancer is currently accepted and widespread worldwide. However, according tol the surgical experience on this approach, surgical and short-term oncologic results may vary. Studies comparing laparoscopic vs. open surgery in our population are scarce. To determine the superiority of the laparoscopic vs. open technique for colorectal cancer surgery. This retrospective and comparative study collected data from patients operated on for colorectal cancer between 1999 and 2011 at the Angeles Lomas Hospital, Mexico. A total of 82 patients were included in this study; 47 were operated through an open approach and 35 laparoscopically. Mean operative time was significantly lower in the open approach group (p= 0.008). There were no significant difference between both techniques for intraoperative bleeding (p= 0.3980), number of lymph nodes (p= 0.27), time to initiate oral feeding (p= 0.31), hospital stay (p= 0.12), and postoperative pain (p= 0.19). Procedure-related complications rate and type were not significantly different in both groups (p= 0.44). Patients operated laparoscopically required significantly less analgesic drugs (p= 0.04) and less need for epidural postoperative analgesia (p= 0.01). Laparoscopic approach is as safe as the traditional open approach for colorectal cancer. Early oncological and surgical results confirm its suitability according to this indication.

  18. Workload and surgeon's specialty for outcome after colorectal cancer surgery

    DEFF Research Database (Denmark)

    Archampong, David; Borowski, David; Wille-Jørgensen, Peer

    2012-01-01

    A large body of research has focused on investigating the effects of healthcare provider volume and specialization on patient outcomes including outcomes of colorectal cancer surgery. However there is conflicting evidence about the role of such healthcare provider characteristics in the management...

  19. The role of tissue factor in colorectal cancer

    DEFF Research Database (Denmark)

    Lykke, J; Nielsen, Hans Jørgen

    2003-01-01

    The possible role of tissue factor (TF) in colorectal cancer (CRC) is reviewed. A correlation between TF expression and advanced stages of malignancy, and a correlation between TF expression and overall survival have been suggested in CRC. This is supported by experimental studies indicating...

  20. Loss of heterozygosity in colorectal cancer | Ozaslan | African ...

    African Journals Online (AJOL)

    Colorectal cancer (CRC) is one of the most common malignancies in the world. The development and progression of CRC is a multistep process, which involves many dietary and environmental factors. A great number of oncogenes, tumour suppressor genes and DNA repair genes contribute to molecular and biological ...

  1. Randomized Comparison of Surveillance Intervals in Familial Colorectal Cancer

    NARCIS (Netherlands)

    Hennink, Simone D.; van der Meulen-de Jong, Andrea E.; Wolterbeek, Ron; Crobach, A. Stijn L. P.; Becx, Marco C. J. M.; Crobach, Wiet F. S. J.; van Haastert, Michiel; ten Hove, W. Rogier; Kleibeuker, Jan H.; Meijssen, Maarten A. C.; Nagengast, Fokko M.; Rijk, Marno C. M.; Salemans, Jan M. J. I.; Stronkhorst, Arnold; Tuynman, Hans A. R. E.; Vecht, Juda; Verhulst, Marie-Louise; Cappel, Wouter H. de Vos Tot Nederveen; Walinga, Herman; Weinhardt, Olaf K.; Westerveld, Dik; Witte, Anne M. C.; Wolters, Hugo J.; Cats, Annemieke; Veenendaal, Roeland A.; Morreau, Hans; Vasen, Hans F. A.

    2015-01-01

    Purpose Colonoscopic surveillance is recommended for individuals with familial colorectal cancer (CRC). However, the appropriate screening interval has not yet been determined. The aim of this randomized trial was to compare a 3-year with a 6-year screening interval. Patients and Methods Individuals

  2. Do lifestyle factors influence colorectal cancer risk in Lynch syndrome?

    NARCIS (Netherlands)

    van Duijnhoven, F.J.B.; Botma, A.; Winkels, R.; Nagengast, F.M.; Vasen, H.F.A.; Kampman, E.

    2013-01-01

    Lynch syndrome (LS) is one of the inherited colorectal cancer (CRC) syndromes and is due to germline mutations in one of the mismatch repair (MMR) genes. Within LS affected-families the expression of the syndrome varies, which suggests that other factors, such as lifestyle factors, have an influence

  3. Colorectal cancer in South Africa: An assessment of disease ...

    African Journals Online (AJOL)

    Patients included in this study were enrolled on the scheme's oncology benefit for the treatment of CRC. International Statistical. This open-access article is distributed under. Creative Commons licence CC-BY-NC 4.0. Colorectal cancer in South Africa: An assessment of disease presentation, treatment pathways and 5-year ...

  4. ORIGINAL ARTICLES Colorectal cancer in South Africa: A heritable ...

    African Journals Online (AJOL)

    The study was approved by the Ethics Committee of the University of the Witwatersrand. (clearance number 9/11/88). From 1990 to 2003, 1 732 black and white South African patients (961 and 771 respectively) with colorectal cancer were identified. Because the study was retrospective, family histories were not obtainable.

  5. Quality of life in colorectal cancer. Stoma vs. nonstoma patients

    NARCIS (Netherlands)

    Sprangers, M. A.; Taal, B. G.; Aaronson, N. K.; te Velde, A.

    1995-01-01

    PURPOSE: The bowel and sexual function of colorectal cancer patients undergoing either sphincter-saving or sphincter-sacrificing surgical procedures may be impaired. A legitimate question is how these different surgical techniques affect the patients' quality of life. METHODS: Seventeen studies were

  6. Genetic alterations of tumor suppressor gene in sporadic colorectal cancers

    Directory of Open Access Journals (Sweden)

    Hadžiavdić Vesna

    2012-01-01

    Full Text Available Colorectal cancer with its frequency, high mortality rate as well as many etiological unknowns is a challenge to contemporary science. Finally, genetic information could be used in near future for prevention of colorectal cancer, its early diagnosis and selection for the most suitable hospital treatment. In this study, we analysed genetic alterations of tumor suppressor genes and the possibility of quick and efficient screening method for identification of colorectal cancer. The study consisted of 54 samples of tumor and surrounding healthy tissue of patients with colorectal cancer, which is clasificated according to Bethesda and Amsterdams criterias. The investigation showed that genetic alterations of tumor suppressor gene NM 23 were present in 19/35 (54,29% samples, and tumor suppressor gene p53 in 18/35 (51,43%, APC in 18/35 (51,43%, DCC2 tumor suppressor gene in 12/35 (34,29%, tumor suppressor gene RB1 in 8 /35 (22, 86% and DCC 1 in 10/35 ( 28,57% tumor tissue.

  7. Serum adipocytokine levels in patients with colorectal cancer

    Directory of Open Access Journals (Sweden)

    Sema Uslu

    2010-12-01

    Full Text Available Objectives: Adipose tissue, besides its main function as an energy storage depot, is currently considered an endocrine organ that secretes several self-produced cytokines. Leptin and resistin play an important role in energy homeostasis, glucose, lipid metabolism and regulation of body weight. The aim of the current study was to determine the concentration of leptin and resistin in pre-operational and post-operational periods of patients diagnosed as colorectal cancer.Materials and methods: The body mass index (BMI and values of leptin and resistin in blood at diagnosis were measured in 12 colorectal cancer patients in pre- and post-operational periods and in 12 age- and sex-matched controls. Serum leptin and resistin concentrations were measured by ELISA method.Results: Decreased leptin (1.95±0.62 ng/ml and resistin (4.32±1.83 ng/ml levels were found in pre-operational group compared with the control group (leptin: 6.12±0.82 ng/ml; resistin: 10.75±1.46 ng/ml (p0.05.Conclusion: We conclude that serum concentration of leptin and resistin may have a role in patients with colorectal cancers. Further studies are needed to investigate the possible prognostic value of leptin and resistin in clinical practice of patients with colorectal cancers.

  8. Microscopical evaluation of prognostic factors in colorectal cancer

    NARCIS (Netherlands)

    Mesker, Wilhelmina Engelina

    2008-01-01

    Aims and outline of the thesis. Since Fearon and Vogelstein in 1990 presented the genetic model for the adeno-carcinoma sequence of colorectal cancer, many prognostic studies varying from early stage markers to markers involved in late progression and liver metastases have followed. As has become

  9. Optimal duration of systemic treatment in metastatic colorectal cancer

    NARCIS (Netherlands)

    Simkens, Lieke H. J.; Koopman, Miriam; Punt, Cornelis J. A.

    2014-01-01

    With the currently available cytotoxic and targeted drugs, metastatic colorectal cancer (mCRC) may be controlled by systemic treatment for a significant period of time. However, many questions remain about the optimal use of drugs and duration of treatment. We reviewed the data from clinical trials

  10. Current treatment for colorectal cancer metastatic to the liver

    NARCIS (Netherlands)

    Cromheecke, M; de Jong, KP; Hoekstra, HJ

    1999-01-01

    Surgery is currently the only available treatment option which offers the potential for cure for patients with liver metastases from colorectal cancer. Of those who undergo a potentially curative operation for their primary tumour but subsequently recur, almost 80% will develop evidence of

  11. [Microsatellite instability in patients with diagnostic of colorectal cancer].

    Science.gov (United States)

    Ortiz, César; Dongo-Pflucker, Kenny; Martín-Cruz, Luis; Barletta Carrillo, Claudia; Mora-Alferez, Pamela; Arias, Abelardo

    2016-01-01

    To determine the presence of microsatellite instability in patients with colorectal cancer using the molecular panel Bethesda and discuss its significance in patients with suspected hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch Syndrome. We worked with samples of peripheral blood and tumor tissue of 28 patients diagnosed with colorectal cancer referred to the Laboratory of Molecular Biology of the Instituto Nacional de Enfermedades Neoplasicas (INEN), Lima, with suspected of Lynch syndrome. DNA was extracted using kits of nucleic acid extraction of peripheral blood and paraffin-embedded tumor tissue. Five microsatellite markers of Bethesda panel were amplified: BAT25, BAT26, D2S123, D5S346 and D17S250, by polymerase chain reaction. IMS analysis was performed by electrophoresis on chip in the Bioanalyzer Agilent 2100. Of the patients studied, 11 had high IMS(IMS-H) and one could not be fully ranked, staying as MSI-H / IMS-L. In all cases of IMS-H both BAT26 and BAT25 were unstable. The IMS-H in these patients indicates high probability of HNPCC or Lynch syndrome; it must be contrasted with the genetic analysis of MMR genes. The technique allowed determine which patients have to continue with the study of system mismatch repair genes, for establish whether we facing to HNPCC or sporadic colorectal cancer.

  12. Mitochondrial microsatellite instability in patients with metastatic colorectal cancer

    NARCIS (Netherlands)

    Venderbosch, S.; van Vliet, S.; Craenmehr, M. H C; Simmer, F.; de Haan, A. F J; Punt, C. J A; Koopman, M.; Nagtegaal, I. D.

    2015-01-01

    Mitochondrial microsatellite instability (mtMSI), a change in length in mtDNA microsatellite sequences between normal and tumor tissue, has been described as a frequent occurrence in colorectal cancer (CRC). We evaluated the prevalence and prognostic value of mtMSI and its relation to nuclear

  13. Candidate driver genes in microsatellite-unstable colorectal cancer

    NARCIS (Netherlands)

    Alhopuro, Pia; Sammalkorpi, Heli; Niittymaki, Iina; Bistrom, Mia; Raitila, Anniina; Saharinen, Juha; Nousiainen, Kari; Lehtonen, Heli J.; Heliovaara, Elina; Puhakka, Jani; Tuupanen, Sari; Sousa, Sonia; Seruca, Raquel; Ferreira, Ana M.; Hofstra, Robert M. W.; Mecklin, Jukka-Pekka; Jarvinen, Heikki; Ristimaki, Ari; Orntoft, Torben F.; Hautaniemi, Sampsa; Arango, Diego; Karhu, Auli; Aaltonen, Lauri A.

    2012-01-01

    Defects in the mismatch repair system lead to microsatellite instability (MSI), a feature observed in similar to 15% of all colorectal cancers (CRCs). Microsatellite mutations that drive tumourigenesis, typically inactivation of tumour suppressors, are selected for and are frequently detected in MSI

  14. Liquid Biopsies in Colorectal Cancer: Monitoring Genetic Heterogeneity.

    Science.gov (United States)

    Gargalionis, Antonios N; Papavassiliou, Athanasios G

    2017-03-01

    Dynamic changes in the colorectal cancer (CRC) signalome and tumor genetic heterogeneity underlie acquired drug resistance. Improving treatment-related decisions is facilitated by an emerging consensus in the classification of tumor subtypes as well as by real-time monitoring of predictive biomarkers in circulating tumor cells and DNA. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Nanoindentation characterisation of human colorectal cancer cells considering cell geometry, surface roughness and hyperelastic constitutive behaviour

    Science.gov (United States)

    Boccaccio, Antonio; Uva, Antonio E.; Papi, Massimiliano; Fiorentino, Michele; De Spirito, Marco; Monno, Giuseppe

    2017-01-01

    Characterisation of the mechanical behaviour of cancer cells is an issue of crucial importance as specific cell mechanical properties have been measured and utilized as possible biomarkers of cancer progression. Atomic force microscopy certainly occupies a prominent place in the field of the mechanical characterisation devices. We developed a hybrid approach to characterise different cell lines (SW620 and SW480) of the human colon carcinoma submitted to nanoindentation measurements. An ad hoc algorithm was written that compares the force-indentation curves experimentally retrieved with those predicted by a finite element model that simulates the nanoindentation process and reproduces the cell geometry and the surface roughness. The algorithm perturbs iteratively the values of the cell mechanical properties implemented in the finite element model until the difference between the experimental and numerical force-indentation curves reaches the minimum value. The occurrence of this indicates that the implemented material properties are very close to the real ones. Different hyperelastic constitutive models, such as Arruda-Boyce, Mooney-Rivlin and Neo-Hookean were utilized to describe the structural behaviour of indented cells. The algorithm was capable of separating, for all the cell lines investigated, the mechanical properties of cell cortex and cytoskeleton. Material properties determined via the algorithm were different with respect to those obtained with the Hertzian contact theory. This demonstrates that factors such as: the cell geometry/anatomy and the hyperelastic constitutive behaviour, which are not contemplated in the Hertz’s theory hypotheses, do affect the nanoindentation measurements. The proposed approach represents a powerful tool that, only on the basis of nanoindentation measurements, is capable of characterising material at the subcellular level.

  16. Prediagnostic smoking history, alcohol consumption, and colorectal cancer survival: the Seattle Colon Cancer Family Registry.

    Science.gov (United States)

    Phipps, Amanda I; Baron, John; Newcomb, Polly A

    2011-11-01

    Smoking and alcohol consumption are associated with an increased risk of developing colorectal cancer. However, it is unclear whether these exposures are associated with survival after colorectal cancer diagnosis. Men and women diagnosed with incident colorectal cancer between 1998 and 2007 in 13 counties in western Washington State were identified by using the Surveillance, Epidemiology, and End Results cancer registry. Information on smoking history and alcohol consumption was collected by telephone interview. Follow-up for mortality was completed through linkage to the National Death Index. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations among smoking, alcohol consumption, and mortality after colorectal cancer diagnosis. Stratified analyses were conducted by sex, age at diagnosis (cancer (HR, 1.08; 95% CI, 0.72-1.61) or those diagnosed before age 50 years (HR, 0.99; 95% CI, 0.67-1.48). Alcohol consumption was not associated with disease-specific or all-cause mortality, regardless of patient or tumor characteristics. In addition to an association with disease risk, smoking is associated with increased mortality after colorectal cancer diagnosis. This association is especially pronounced for colorectal cancer with high microsatellite instability. Copyright © 2011 American Cancer Society.

  17. Familial colorectal cancer type X: polyp burden and cancer risk stratification via a family history score.

    Science.gov (United States)

    Koh, Poh-Koon; Kalady, Matthew; Skacel, Marek; Fay, Susan; McGannon, Ellen; Shenal, Janet; Arroyo, Loretta; Toderick, Kathy; Church, James

    2011-01-01

    Patients fulfilling Amsterdam-1 criteria without mismatch repair deficiency (termed familial colorectal cancer type X (FCC type X)) were reported to have lower cancer risks than classic Lynch syndrome. This study investigates the polyp and cancer burden of this population and demonstrates relationships with a family history score (FHS). The Jagelman Registry was queried for patients meeting Amsterdam criteria with microsatellite stable/low colorectal cancers. The risk of colorectal neoplasia was ascertained using a published FHS. Polyp distribution, histology and cumulative counts as well as extra-colonic tumours in the pedigree were reviewed. Twenty-one patients (9 males, 12 females) met study criteria. The median lifetime polyp count was 3 (range 1–36). FHS 8 (80%) was significantly associated with an increased risk of colorectal cancer compared with those with scores colorectal cancers (7 left-sided, 3 right-sided) were diagnosed at a median age of 48 (range 30–74) years. Only three tumours were mucinous or demonstrated tumour-infiltrating lymphocytes, typical of high microsatellite instability tumours. All patients had family history of colorectal cancers (CRCs) and at least 10 patients had a family history of uterine or breast cancer. One patient was found to have hyperplastic polyposis syndrome. FCC type X likely represents a heterogenous group of as yet undefined CRC predispositions. The polyp burden and cancer risk are variable and can be somewhat delineated according to an FHS.

  18. Hyaluronan and calcium carbonate hybrid nanoparticles for colorectal cancer chemotherapy

    Science.gov (United States)

    Bai, Jinghui; Xu, Jian; Zhao, Jian; Zhang, Rui

    2017-09-01

    A hybrid drug delivery system (DDS) composed of hyaluronan and calcium carbonate (CC) was developed. By taking advantage of the tumor-targeting ability of hyaluronan and the drug-loading property of CC, the well-formed hyaluronan-CC nanoparticles were able to serve as a DDS targeting colorectal cancer with a decent drug loading content, which is beneficial in the chemotherapy of colorectal cancer. In this study, hyaluronan-CC nanoparticles smaller than 100 nm were successfully developed to load the wide-range anti-cancer drug adriamycin (Adr) to construct hyaluronan-CC/Adr nanoparticles. On the other hand, we also found that hyaluronan-CC/Adr nanoparticles can possibly increase the uptake ratio of Adr into HT29 colorectal cancer cells when compared with hyaluronan-free nanoparticles (CC/Adr) via the CD44 receptor-mediated endocytosis via competitive uptake and in vivo imaging assays. Note that both in vitro (CCK-8 assay on HT29 cells) and in vivo (anti-cancer assay on HT-29 tumor-bearing nude mice model) experiments revealed that hyaluronan-CC/Adr nanoparticles exhibited stronger anti-cancer activity than free Adr or CC/Adr nanoparticles with minimized toxic side effects and preferable cancer-suppression potential.

  19. Genetics and Genetic Testing in Hereditary Colorectal Cancer.

    Science.gov (United States)

    Stoffel, Elena M; Boland, C Richard

    2015-10-01

    Colorectal cancer (CRC) remains the third most common cancer affecting men and women in the United States. Approximately one-third of CRCs are diagnosed in individuals who have family members also affected with the disease. Although the vast majority of colorectal neoplasms develop as a consequence of somatic genomic alterations arising in individual cells, approximately 5% of all CRCs arise in the setting of germline mutations in genes involved in key cellular processes. To date, multiple genes have been implicated in single-gene hereditary cancer syndromes, many of which are associated with increased risk for CRC, as well as other tumor types. This review outlines the clinical, pathologic, and genetic features of the hereditary cancer syndromes known to be associated with increased risk for CRC and delineates strategies for implementing genetic risk assessments in clinical settings. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  20. Fear of cancer recurrence in colorectal cancer survivors.

    Science.gov (United States)

    Custers, José A E; Gielissen, Marieke F M; Janssen, Stephanie H V; de Wilt, Johannes H W; Prins, Judith B

    2016-02-01

    Although long-term colorectal cancer (CRC) survivors generally report a good quality of life, fear of cancer recurrence (FCR) remains an important issue. This study investigated whether the Cancer Worry Scale (CWS) can detect high FCR, the prevalence, and characteristics of FCR in CRC survivors. Two hundred and eleven patients who had undergone successful CRC surgery in the period 2003-2010 in the Radboud University Medical Center in the Netherlands were asked to participate. All patients were sent an information letter plus questionnaires for collecting information on demographic and medical variables, FCR, distress, and quality of life. Seventy-six patients (36 %; median age of 67.7 years range 41-88 years) completed the questionnaires a median of 5.1 years after surgery. A cut-off score of 14 or higher on the CWS was optimal to detect high FCR. Twenty-nine patients (38 %) experienced high levels of FCR, characterized by higher levels of distress, post-traumatic stress symptoms, and lower quality of life. These individuals particularly reacted to disease-related triggers, felt helpless, were worried, and experienced limitations in daily functioning. High FCR was not associated with demographic or medical variables. Long after successful CRC surgery, FCR is a serious problem that impairs the quality of life for a substantial proportion of patients. With the CWS, it is possible to detect high FCR and thereby assist survivors in receiving appropriate care.

  1. Evidence for field effect cancerization in colorectal cancer.

    Science.gov (United States)

    Hawthorn, L; Lan, L; Mojica, W

    2014-01-01

    We compared transcript expression, and chromosomal changes on a series of tumors and surrounding tissues to determine if there is evidence of field cancerization in colorectal cancer. Epithelial cells were isolated from tumors and areas adjacent to the tumors ranging from 1 to 10cm. Tumor abnormalities mirrored those previously reported for colon cancer and while the number and size of the chromosomal abnormalities were greatly reduced in cells from surrounding regions, many chromosome abnormalities were discernable. Interestingly, these abnormalities were not consistent across the field in the same patient samples suggesting a field of chromosomal instability surrounding the tumor. A mutator phenotype has been proposed to account for this instability which states that the genotypes of cells within a tumor would not be identical, but would share at least a single mutation in any number of genes, or a selection of genes affecting a specific pathway which provide a proliferative advantage. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Designing the colorectal cancer core dataset in Iran

    Directory of Open Access Journals (Sweden)

    Sara Dorri

    2017-01-01

    Full Text Available Background: There is no need to explain the importance of collection, recording and analyzing the information of disease in any health organization. In this regard, systematic design of standard data sets can be helpful to record uniform and consistent information. It can create interoperability between health care systems. The main purpose of this study was design the core dataset to record colorectal cancer information in Iran. Methods: For the design of the colorectal cancer core data set, a combination of literature review and expert consensus were used. In the first phase, the draft of the data set was designed based on colorectal cancer literature review and comparative studies. Then, in the second phase, this data set was evaluated by experts from different discipline such as medical informatics, oncology and surgery. Their comments and opinion were taken. In the third phase refined data set, was evaluated again by experts and eventually data set was proposed. Results: In first phase, based on the literature review, a draft set of 85 data elements was designed. In the second phase this data set was evaluated by experts and supplementary information was offered by professionals in subgroups especially in treatment part. In this phase the number of elements totally were arrived to 93 numbers. In the third phase, evaluation was conducted by experts and finally this dataset was designed in five main parts including: demographic information, diagnostic information, treatment information, clinical status assessment information, and clinical trial information. Conclusion: In this study the comprehensive core data set of colorectal cancer was designed. This dataset in the field of collecting colorectal cancer information can be useful through facilitating exchange of health information. Designing such data set for similar disease can help providers to collect standard data from patients and can accelerate retrieval from storage systems.

  3. GUCY2C ligand replacement to prevent colorectal cancer

    OpenAIRE

    Blomain, Erik S.; Pattison, Amanda M.; Waldman, Scott A.

    2016-01-01

    Despite advances in screening and prevention strategies, colorectal cancer (CRC) remains the second-leading cause of cancer-related death in the United States. Given this continued public health burden of CRC, there is a clear need for improved disease prevention. CRC initiates and progresses over decades, canonically proceeding via a series of stepwise molecular events that turn a normal epithelium into a dysfunctional epithelium, then subsequently into an adenoma, and finally an invasive ad...

  4. Circulating tumor cells: Exploring intratumor heterogeneity of colorectal cancer

    OpenAIRE

    Raimondi, Cristina; Nicolazzo, Chiara; Gradilone, Angela; Giannini, Giuseppe; de Falco, Elena; Chimenti, Isotta; Varriale, Elisa; Hauch, Siegfried; Plappert, Linda; Cortesi, Enrico; Gazzaniga, Paola

    2014-01-01

    The hypothesis of the “liquid biopsy” using circulating tumor cells (CTCs) emerged as a minimally invasive alternative to traditional tissue biopsy to determine cancer therapy. Discordance for biomarkers expression between primary tumor tissue and circulating tumor cells (CTCs) has been widely reported, thus rendering the biological characterization of CTCs an attractive tool for biomarkers assessment and treatment selection. Studies performed in metastatic colorectal cancer (mCRC) patients u...

  5. Towards the human colorectal cancer microbiome

    NARCIS (Netherlands)

    Marchesi, J.R.; Dutilh, B.E.; Hall, N.; Peters, W.H.M.; Roelofs, R.; Boleij, A.; Tjalsma, H.

    2011-01-01

    Multiple factors drive the progression from healthy mucosa towards sporadic colorectal carcinomas and accumulating evidence associates intestinal bacteria with disease initiation and progression. Therefore, the aim of this study was to provide a first high-resolution map of colonic dysbiosis that is

  6. Outcome of colorectal cancer resection in octogenarians

    African Journals Online (AJOL)

    Absolute number of postoperative complications in patients aged >80 years and 60 - 70 years undergoing colorectal resection (CVA = cerebrovascular accident; DVT = deep-vein thrombosis; PE = pulmonary embolism; CDT = Clostridium difficile; UTI = urinary tract infection; MI = myocardial infarction; AF = atrial fibrillation).

  7. 76 FR 41805 - Submission for OMB Review; Comment Request; Prostate, Lung, Colorectal and Ovarian Cancer...

    Science.gov (United States)

    2011-07-15

    ... Collection: Title: Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) (NCI). Type of... ovarian cancer can reduce mortality from these cancers which currently cause an estimated 254,570 deaths... (prostate, lung, colorectal, and ovary). In addition, cancer incidence, stage shift, and case survival are...

  8. Colorectal cancer in Mauritius: facts and figures -‐ A ten year ...

    African Journals Online (AJOL)

    Among the various types of cancers in Mauritius, colorectal cancer has evolved as 1st in male and 3rd in female in 2008 (National Cancer Action Plan 2010 MOH & QL, Mauritius). Colorectal cancer is one of the leading causes of death worldwide. A retrospective study of 10 years (2001-‐2010) has been carried out using ...

  9. SLIT2 axon guidance molecule is frequently inactivated in colorectal cancer and suppresses growth of colorectal carcinoma cells.

    Science.gov (United States)

    Dallol, Ashraf; Morton, Dion; Maher, Eamonn R; Latif, Farida

    2003-03-01

    We have shown recently that SLIT2 has tumor suppressor activity and that it is epigenetically silenced in >40% of lung and breast tumors. In this study, we have analyzed the methylation status of SLIT2 in primary colorectal cancers and matching normal colorectal mucosa. SLIT2 promoter region methylation was found in 23 (72%) of 32 primary colorectal cancers. In contrast, normal colorectal mucosa from the same patients exhibited significantly lower levels of SLIT2 promoter region hypermethylation. SLIT2 methylation was reversed and expression restored by treating colorectal tumor cell lines with the demethylating agent 5-aza-2-deoxycytidine. Loss of heterozygosity at D4S1546 marker, which maps within 100 kb of the SLIT2 gene, was observed in 39% of the methylated tumors. Furthermore, SLIT2 epigenetic silencing was independent of ROBO1/p16/RASSF1A hypermethylation. The presence of SLIT2 methylation was also independent of the presence of K-RAS mutations. Ectopic expression of SLIT2 diminished the ability to form colonies in two colorectal tumor cell lines. In addition, conditioned medium from SLIT2-transfected COS-7 cells reduced cell growth and induced apoptosis in SW48 colorectal tumor cell line. In conclusion, SLIT2 is an excellent candidate tumor suppressor gene for colorectal cancer.

  10. Replication error deficient and proficient colorectal cancer gene expression differences caused by 3'UTR polyT sequence deletions

    DEFF Research Database (Denmark)

    Wilding, Jennifer L; McGowan, Simon; Liu, Ying

    2010-01-01

    Replication error deficient (RER+) colorectal cancers are a distinct subset of colorectal cancers, characterized by inactivation of the DNA mismatch repair system. These cancers are typically pseudodiploid, accumulate mutations in repetitive sequences as a result of their mismatch repair deficiency...

  11. Liver-directed therapy in metastatic colorectal cancer.

    Science.gov (United States)

    Kelly, Ciara M; Kemeny, Nancy E

    2017-08-01

    Colorectal cancer is a significant global health issue with over 1 million cases diagnosed annually throughout the world. 15% of patients diagnosed with colorectal cancer will have liver metastases and 60% will develop liver metastases if they have metastatic disease. Oligometastatic colorectal cancer confined to the liver represents an intermediate state in the evolution of metastatic capacity that opens the opportunity for local interventions. Areas covered: The literature supports long-term survival if patients undergo liver resection of colorectal metastases. This article reviews the liver-directed therapeutic strategies available for the management of metastatic liver disease including hepatic arterial infusion therapy, radiofrequency ablation, radiation therapy and transarterial chemoembolization. Expert commentary: Great advances have been made with the use of liver directed therapies. In the USA using hepatic arterial infusions with FUDR and Decadron along with systemic therapy, 5 year survivals after liver resection have improved. In Europe with the use of HAI of Oxaliplatin, more patients have been able to get to resection and have obtained higher survival rates, even in second line therapy. New advances in ablative therapy have improved results to get all disease treated at resection for the treatment of reccurrence.

  12. Interleukin-17: A Promoter in Colorectal Cancer Progression

    Science.gov (United States)

    Wu, Pin; Huang, Qi; Liu, Yang

    2013-01-01

    It is widely accepted that chronic inflammation plays an active role in cancer. Inflammatory immunocytes and related cytokines in the tumor microenvironment are supposed to be a “double-edged sword” in colorectal cancer (CRC) initiation and progression. Interleukin-17 (IL-17), a pleiotropic proinflammatory cytokine, can promote cancer-elicited inflammation and prevent cancer cells from immune surveillance. Despite controversy, IL-17 is generally considered to be a promoter in CRC progression. In this review, we devote to summarize the current progress regarding the role of IL-17 in tumor initiation and progression, as well as the prognostic value in CRC. PMID:24382972

  13. Clinical and Biological Features of Interval Colorectal Cancer.

    Science.gov (United States)

    Lee, Yu Mi; Huh, Kyu Chan

    2017-05-01

    Interval colorectal cancer (I-CRC) is defined as a CRC diagnosed within 60 months after a negative colonoscopy, taking into account that 5 years is the "mean sojourn time." It is important to prevent the development of interval cancer. The development of interval colon cancer is associated with female sex, old age, family history of CRC, comorbidities, diverticulosis, and the skill of the endoscopist. During carcinogenesis, sessile serrated adenomas/polyps (SSA/Ps) share many genomic and colonic site characteristics with I-CRCs. The clinical and biological features of I-CRC should be elucidated to prevent the development of interval colon cancer.

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

    Science.gov (United States)

    Allsopp, Philip; Rowland, Ian

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

  15. Stage II colorectal cancer: lack of prognostic model

    Directory of Open Access Journals (Sweden)

    Abdelbaset Buhmeida

    2007-01-01

    Full Text Available TO THE EDITOR: Colorectal cancer (CRC is one of the most common malignant tumors worldwide (Gatta et al. 1998 [1], Repetto et al. 2003 [2] with the disease incidence rising along with an advanced age (Wymenga et al. 2001 [3], Franceschi et al. 2001 [4]. The overall mortality from CRC is 60%, which represents the second leading cause of cancer death in western societies. In Finland, the incidence of CRC is 25/100.000, and 20/100.000 among males and females, respectively. Annually, 1.150 new cases are detected among males and 1.200 among women, representing 9.2% and 10% of all cancer cases, respectively (Finnish Cancer Registry, 2005. On the other hand, according to Benghazi Cancer Registry, 2003 [5] the colorectal cancer in eastern part of Libya is the most second frequent cancer after lung cancer in males and breast cancer in females. The average crude incidence rate is 6.4 (male and 5.2 (female cases per 100,000 inhabitants, representing 10.1% of male patients and 9.3% of female patients of all cancer cases.

  16. Age-specific incidence of all neoplasms after colorectal cancer.

    Science.gov (United States)

    Levi, Fabio; Randimbison, Lalao; Blanc-Moya, Rafael; La Vecchia, Carlo

    2014-10-01

    Patients diagnosed with a specific neoplasm tend to have a subsequent excess risk of the same neoplasm. The age incidence of a second neoplasm at the same site is approximately constant with age, and consequently the relative risk is greater at younger age. It is unclear whether such a line of reasoning can be extended from a specific neoplasm to the incidence of all neoplasms in subjects diagnosed with a defined neoplasm. We considered the age-specific incidence of all non-hormone-related epithelial neoplasms after a first primary colorectal cancer (n = 9542) in the Vaud Cancer Registry data set. In subjects with a previous colorectal cancer, the incidence rate of all other epithelial non-hormone-related cancers was stable around 800 per 100,000 between age 30 and 60 years, and rose only about twofold to reach 1685 at age 70 to 79 years and 1826 per 100,000 at age 80 years or older. After excluding synchronous cancers, the rise was only about 1.5-fold, that is, from about 700 to 1000. In the general population, the incidence rate of all epithelial non-hormone-related cancers was 29 per 100,000 at age 30 to 39 years, and rose 30-fold to 883 per 100,000 at age 70 to 79 years. Excluding colorectal cancers, the rise of all non-hormone-related cancers was from 360 per 100,000 at age 40 to 49 years to 940 at age 70 to 79 years after colorectal cancer, and from 90 to 636 per 100,000 in the general population (i.e., 2.6- vs. 7.1-fold). The rise of incidence with age of all epithelial non-hormone-related second cancers after colorectal cancer is much smaller than in the general population. This can possibly be related to the occurrence of a single mutational event in a population of susceptible individuals, although alternative models are plausible within the complexity of the process of carcinogenesis. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2010-12-01

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

  18. Identification of mismatch repair gene mutations in young patients with colorectal cancer and in patients with multiple tumours associated with hereditary non-polyposis colorectal cancer.

    NARCIS (Netherlands)

    Niessen, R.C.; Berends, M.J.; Wu, Y.; Sijmons, R.H.; Hollema, H.; Ligtenberg, M.J.L.; Walle, H.E. de; Vries, E.G.F. de; Karrenbeld, A.; Buys, C.H.C.M.; Zee, A.G. van der; Hofstra, R.M.; Kleibeuker, J.H.

    2006-01-01

    BACKGROUND: Patients with early-onset colorectal cancer (CRC) or those with multiple tumours associated with hereditary non-polyposis colorectal cancer (HNPCC) raise suspicion of the presence of germline DNA mismatch repair (MMR) gene mutations. AIM: To analyse the value of family history,

  19. Identification of mismatch repair gene mutations in young patients with colorectal cancer and in patients with multiple tumours associated with hereditary non-polyposis colorectal cancer

    NARCIS (Netherlands)

    Niessen, R C; Berends, M J W; Wu, Y; Sijmons, R H; Hollema, H; Ligtenberg, M J L; de Walle, H E K; de Vries, E G E; Karrenbeld, A; Buys, C H C M; van der Zee, A G J; Hofstra, R M W; Kleibeuker, J H

    2006-01-01

    Background: Patients with early-onset colorectal cancer (CRC) or those with multiple tumours associated with hereditary non-polyposis colorectal cancer (HNPCC) raise suspicion of the presence of germline DNA mismatch repair (MMR) gene mutations. Aim: To analyse the value of family history,

  20. Seromic profiling of colorectal cancer patients with novel glycopeptide microarray

    DEFF Research Database (Denmark)

    Pedersen, Johannes W; Blixt, Ola; Bennett, Eric P

    2011-01-01

    array displaying a comprehensive library of glycopeptides and glycoproteins derived from a panel of human mucins (MUC1, MUC2, MUC4, MUC5AC, MUC6 and MUC7) known to have altered glycosylation and expression in cancer. Seromic profiling of patients with colorectal cancer identified cancer......Cancer-associated autoantibodies hold promise as sensitive biomarkers for early detection of cancer. Aberrant post-translational variants of proteins are likely to induce autoantibodies, and changes in O-linked glycosylation represent one of the most important cancer-associated post......-associated autoantibodies to a set of aberrant glycopeptides derived from MUC1 and MUC4. The cumulative sensitivity of the array analysis was 79% with a specificity of 92%. The most prevalent of the identified autoantibody targets were validated as authentic cancer immunogens by showing expression of the epitopes in cancer...

  1. Gender-associated genomic differences in colorectal cancer: clinical insight from feminization of male cancer cells

    National Research Council Canada - National Science Library

    Ali, Rola H; Marafie, Makia J; Bitar, Milad S; Al-Dousari, Fahad; Ismael, Samar; Bin Haider, Hussain; Al-Ali, Waleed; Jacob, Sindhu P; Al-Mulla, Fahd

    2014-01-01

    Gender-related differences in colorectal cancer (CRC) are not fully understood. Recent studies have shown that CRC arising in females are significantly associated with CpG island methylator phenotype (CIMP-high...

  2. Collagen mRNA levels changes during colorectal cancer carcinogenesis

    DEFF Research Database (Denmark)

    Skovbjerg, Hanne; Anthonsen, Dorit; Lothe, Inger M B

    2009-01-01

    . In addition, corresponding tissue was examined from healthy volunteers (n = 20). mRNA levels were normalized to beta-actin. Immunohistochemical analysis of the distributions of type IV and type VII collagens were performed on normal and affected tissues from colorectal cancer patients. RESULTS: The alpha1(IV......). The level of alpha 6(IV) was 5-fold lower in colorectal cancer tissue as compared to healthy individuals (p alpha 6(IV) mRNA coincides...... zone of stratified epithelia. Immunohistochemical studies have previously reported changes in steady-state levels of different alpha(IV) chains in several epithelial cancer types. In the present study we aimed to quantitatively determine the mRNA levels of type IV collagen (alpha1/alpha 4/alpha 6...

  3. Serrated Polyposis: An Enigmatic Model of Colorectal Cancer Predisposition

    Science.gov (United States)

    Rosty, Christophe; Parry, Susan; Young, Joanne P.

    2011-01-01

    Serrated polyposis has only recently been accepted as a condition which carries an increased personal and familial risk of colorectal cancer. Described over four decades ago, it remains one of the most underrecognized and poorly understood of all the intestinal polyposes. With a variety of phenotypic presentations, it is likely that serrated polyposis represents a group of diseases rather than a single entity. Further, neoplastic progression in serrated polyposis may be associated with premature aging in the normal mucosa, typified by widespread gene promoter hypermethylation. From this epigenetically altered field, arise diverse polyps and cancers which show a range of molecular features. Despite a high serrated polyp count, only one-third of colorectal cancers demonstrate a BRAF V600E mutation, the molecular hallmark of the canonical serrated pathway, suggesting that though multiple serrated polyps act as a marker of an abnormal mucosa, the majority of CRC in these patients arise within lesions other than BRAF-mutated serrated polyps. PMID:21660283

  4. Animal models of colorectal cancer with liver metastasis.

    Science.gov (United States)

    Oh, Bo Young; Hong, Hye Kyung; Lee, Woo Yong; Cho, Yong Beom

    2017-02-28

    Liver metastasis is a leading cause of death in patients with colorectal cancer. Investigating the mechanisms of liver metastasis and control of disease progression are important strategies for improving survival of these patients. Liver metastasis is a multi-step process and relevant models representing these steps are necessary to understand the mechanism of liver metastasis and establish appropriate treatments. Recently, the development of animal models for use in metastasis research has greatly increased; however, there is still a lack of models that sufficiently represent human cancer. Thus, in order to select an optimal model for of a given study, it is necessary to fully understand the characteristics of each animal model. In this review, we describe the mouse models currently used for colorectal cancer with liver metastasis, their characteristics, and their pros and cons. This may help us specify the mechanism of liver metastasis and provide evidence relevant to clinical applications. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Assessment of rehabilitation needs in colorectal cancer treatment

    DEFF Research Database (Denmark)

    Wiedenbein, Liza; Kristiansen, Maria; Adamsen, Lis

    2016-01-01

    Background Systematic assessments of cancer patients' rehabilitation needs are a prerequisite for devising appropriate survivorship programs. Little is known about the fit between needs assessment outlined in national rehabilitation policies and clinical practice. This study aimed to explore...... clinical practices related to identification and documentation of rehabilitation needs among patients with colorectal cancer at Danish hospitals. Material and methods A retrospective clinical audit was conducted utilizing data from patient files randomly selected at surgical and oncology hospital...... departments treating colorectal cancer patients. Forty patients were included, 10 from each department. Semi-structured interviews were carried out among clinical nurse specialists. Audit data was analyzed using descriptive statistics, qualitative data using thematic analysis. Results Documentation...

  6. The clinical perspectives of CDX2 expression in colorectal cancer

    DEFF Research Database (Denmark)

    Olsen, Jesper; Espersen, Maiken Lise Marcker; Jess, P

    2014-01-01

    , however the expression pattern may often be heterogeneous within the tumor and can be selectively down regulated at the invasive front and in tumor buddings. Loss of CDX2 expression is probably correlated to tumor grade, stage, right-sided tumor location, MMR-deficiency, CIMP, and BRAF mutations. The CDX2......Homeobox genes are often deregulated in cancer. They can have both oncogenic and tumor-suppressing potential. The Caudal-related homeobox transcription factor 2 (CDX2) is an intestine-specific transcription factor. It is implicated in differentiation, proliferation, cell-adhesion, and migration....... CDX2 has been proposed as a tumor suppressor in colorectal cancer but its role is still controversial. This systematic review were undertaken in order to clarify CDX2s role in colorectal cancer. METHODS: A literature search was performed in the MEDLINE database from 1966 to February 2014. Only studies...

  7. Dietary Modulation of Inflammation-Induced Colorectal Cancer through PPARγ

    Directory of Open Access Journals (Sweden)

    Ashlee B. Carter

    2009-01-01

    Full Text Available Mounting evidence suggests that the risk of developing colorectal cancer (CRC is dramatically increased for patients with chronic inflammatory diseases. For instance, patients with Crohn's Disease (CD or Ulcerative Colitis (UC have a 12–20% increased risk for developing CRC. Preventive strategies utilizing nontoxic natural compounds that modulate immune responses could be successful in the suppression of inflammation-driven colorectal cancer in high-risk groups. The increase of peroxisome proliferator-activated receptor-γ (PPAR-γ expression and its transcriptional activity has been identified as a target for anti-inflammatory efforts, and the suppression of inflammation-driven colon cancer. PPARγ down-modulates inflammation and elicits antiproliferative and proapoptotic actions in epithelial cells. All of which may decrease the risk for inflammation-induced CRC. This review will focus on the use of orally active, naturally occurring chemopreventive approaches against inflammation-induced CRC that target PPARγ and therefore down-modulate inflammation.

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

    Directory of Open Access Journals (Sweden)

    C. Quantin

    2012-01-01

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

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

    KAUST Repository

    Cima, Igor

    2016-06-29

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

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

    Science.gov (United States)

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

    2012-01-01

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

  11. Is obesity an advantage in patients with colorectal cancer?

    Science.gov (United States)

    Kasi, Pashtoon Murtaza; Zafar, S Yousuf; Grothey, Axel

    2015-01-01

    Obesity/higher BMI appears to be important determinants in the development of colon cancer as well as in predicting outcomes in the adjuvant setting in these patients. These associations seem to be stronger for men and tend to be 'J-shaped', with worse outcomes in both lower and upper BMI categories than in the middle categories. How this factors in the metastatic setting is less clear. A recent pooled analysis of patients with metastatic colorectal cancer receiving bevacizumab in the first-line setting observed that patients with the lowest BMI had the lowest median overall survival. An incremental BMI increase of 5 kg/m(2) led to actually a decrease in the risk of death (hazard ratio, 0.911 [95% CI, 0.879-0.944]). The observed association does not necessarily mean that obesity is an advantage for patients with metastatic colorectal cancer. More likely, it is conceivable that, in patients with metastatic colorectal cancer with a lower BMI, the effects of cancer-related cachexia may be more deleterious than the potential adverse events related to a higher BMI. In patients already diagnosed with metastatic disease, studying how body weight affects tumor biology and treatment-related decisions are important considerations.

  12. Brief Report: Family cancer history affecting risk of colorectal cancer in a prospective cohort of Chinese women

    OpenAIRE

    Murphy, Gwen; Shu, Xiao Ou; Gao, Yu-Tang; Ji, Bu-Tian; Cook, Michael Blaise; Yang, Gong; Li, Hong-Lan; Rothman, Nathaniel; Zheng, Wei; Chow, Wong-Ho

    2009-01-01

    An elevated risk of colorectal cancer has been associated with sporadic colorectal cancer in first degree relatives, mostly in Western populations. Limited data exists from traditionally low-risk areas, such as Asia, where the prevalence of risk factors may differ. We examined the association of family history of cancer and subsequent colorectal cancer risk in a cohort of traditionally low-risk Chinese women.

  13. Prognostic stratification of colorectal cancer patients: current perspectives

    Directory of Open Access Journals (Sweden)

    Schneider NI

    2014-07-01

    Full Text Available Nora I Schneider, Cord LangnerInstitute of Pathology, Medical University of Graz, Graz, AustriaAbstract: Tumor staging according to the American Joint Committee on Cancer/Union for International Cancer Control tumor, node, metastasis (TNM system is currently regarded as the standard for staging of patients with colorectal cancer. This system provides the strongest prognostic information for patients with early stage disease and those with advanced disease. For patients with intermediate levels of disease, it is less able to predict disease outcome. Therefore, additional prognostic markers are needed to improve the management of affected patients. Ideal markers are readily assessable on hematoxylin and eosin-stained tumor slides, and in this way are easily applicable worldwide. This review summarizes the histological features of colorectal cancer that can be used for prognostic stratification. Specifically, we refer to the different histological variants of colorectal cancer that have been identified, each of these variants carrying distinct prognostic significance. Established markers of adverse outcomes are lymphatic and venous invasion, as well as perineural invasion, but underreporting still occurs in the routine setting. Tumor budding and tumor necrosis are recent advances that may help to identify patients at high risk for recurrence. The prognostic significance of the antitumor inflammatory response has been known for quite a long time, but a lack of standardization prevented its application in routine pathology. However, scales to assess intra- and peritumoral inflammation have recently emerged, and can be expected to strengthen the prognostic significance of the pathology report.Keywords: colorectal cancer, lymphatic invasion, blood-vessel invasion, perineural invasion, tumor budding, tumor necrosis

  14. Cancer Susceptibility Gene Mutations in Individuals With Colorectal Cancer.

    Science.gov (United States)

    Yurgelun, Matthew B; Kulke, Matthew H; Fuchs, Charles S; Allen, Brian A; Uno, Hajime; Hornick, Jason L; Ukaegbu, Chinedu I; Brais, Lauren K; McNamara, Philip G; Mayer, Robert J; Schrag, Deborah; Meyerhardt, Jeffrey A; Ng, Kimmie; Kidd, John; Singh, Nanda; Hartman, Anne-Renee; Wenstrup, Richard J; Syngal, Sapna

    2017-04-01

    Purpose Hereditary factors play an important role in colorectal cancer (CRC) risk, yet the prevalence of germline cancer susceptibility gene mutations in patients with CRC unselected for high-risk features (eg, early age at diagnosis, personal/family history of cancer or polyps, tumor microsatellite instability [MSI], mismatch repair [MMR] deficiency) is unknown. Patients and Methods We recruited 1,058 participants who received CRC care in a clinic-based setting without preselection for age at diagnosis, personal/family history, or MSI/MMR results. All participants underwent germline testing for mutations in 25 genes associated with inherited cancer risk. Each gene was categorized as high penetrance or moderate penetrance on the basis of published estimates of the lifetime cancer risks conferred by pathogenic germline mutations in that gene. Results One hundred five (9.9%; 95% CI, 8.2% to 11.9%) of 1,058 participants carried one or more pathogenic mutations, including 33 (3.1%) with Lynch syndrome (LS). Twenty-eight (96.6%) of 29 available LS CRCs demonstrated abnormal MSI/MMR results. Seventy-four (7.0%) of 1,058 participants carried non-LS gene mutations, including 23 (2.2%) with mutations in high-penetrance genes (five APC, three biallelic MUTYH, 11 BRCA1/2, two PALB2, one CDKN2A, and one TP53), 15 of whom lacked clinical histories suggestive of their underlying mutation. Thirty-eight (3.6%) participants had moderate-penetrance CRC risk gene mutations (19 monoallelic MUTYH, 17 APC*I1307K, two CHEK2). Neither proband age at CRC diagnosis, family history of CRC, nor personal history of other cancers significantly predicted the presence of pathogenic mutations in non-LS genes. Conclusion Germline cancer susceptibility gene mutations are carried by 9.9% of patients with CRC. MSI/MMR testing reliably identifies LS probands, although 7.0% of patients with CRC carry non-LS mutations, including 1.0% with BRCA1/2 mutations.

  15. Detection of hypermethylated spastic paraplegia-20 in stool samples of patients with colorectal cancer.

    Science.gov (United States)

    Zhang, Hao; Song, Yong-Chun; Dang, Cheng-Xue

    2013-01-01

    Analysis of aberrant hypermethylation in stool DNA might provide a novel strategy for noninvasive detection of colorectal cancer. To explore the feasibility of detecting hypermethylation in Spastic paraplegia-20 promoter as a stool-based DNA marker for detection of colorectal cancer. We collected 96 tissue and stool samples from patients with colorectal cancer and 30 stool samples healthy individuals. Hypermethylated Spastic paraplegia-20 occurs in 85.4% (82/96) of patients with colorectal cancer in the tissue samples. In the stool samples, the results indicate 80.2% (77/96) sensitivity and 100% (30/30) specificity of the test for detecting colorectal cancer by using the stool samples as a noninvasive method. The study reveals that hypermethylation in Spastic paraplegia-20 promoter is a highly specific and sensitive biomarker for screening colorectal cancer in stool samples as a noninvasive method.

  16. The comparasion of microsatellite instability at sporadic colorectal and hereditary non-polyposis colorectal cancers

    Directory of Open Access Journals (Sweden)

    Hadžiavdić Vesna

    2012-01-01

    Full Text Available Somatic mutations of MMR gene are not often present in HNPCC and in sporadic RER+ colorectal cancers. Complete studies were made according to Bethesda and Amsterdam Criteria, and 35 patients belonged to the group with sporadic colorectal cancer, and 9 patients belonged to HNPCC group. The results of our studies showed that there is no significant difference between RER phenotype of HNPCC and sporadic cancer (p>0,05 in regard to microsatellite status. It can be a good indicator that there are so called 'susspected' on HNPCC among sporadic cancers which were not detected yet. The reason for this was an incomplete familial history of illness of patients and as such it was selected as sporadic cancer. Microsatellite analysis together with medical and familial history of illness can be a successful instrument for efficient HNPCC identification. However, successful solving of this problem lies in making an accurate diagnosis in comparative findings, which can be provided by genetic and clinical tests.

  17. CT colonography for synchronous colorectal lesions in patients with colorectal cancer: initial experience.

    Science.gov (United States)

    McArthur, D R; Mehrzad, H; Patel, R; Dadds, J; Pallan, A; Karandikar, S S; Roy-Choudhury, S

    2010-03-01

    To assess accuracy of CT colonography (CTC) in identifying synchronous lesions in patients with colorectal carcinoma. This study included 174 consecutive patients undergoing CTC as part of staging or primary investigation where a colorectal cancer was diagnosed between 2004 and 2007. Prone unenhanced and portal phase enhanced supine series with air or CO(2) distension were acquired using 4- or 16-slice CT (Toshiba) and read by 2D +/- 3D formats. Synchronous lesions were classified according to American College of Radiology's (ACR) polyp classification. Segmental gold standard was flexible sigmoidoscopy/colonoscopy within 1 year and/or histology of colonic resection supplemented by follow-up. Nine patients without gold standard were excluded. Sensitivity, specificity and accuracy were calculated on a per polyp, per patient and per segment basis and discrepancies analysed. Direct comparable data were available for 764/990 colonic segments from 165 patients. Of 41 (C2-C4) synchronous lesions on "gold standard", 33 were correctly identified on virtual colonoscopy (VC), overall per polyp sensitivity was 80.5%, with detection rates of 20/24 C3 (83.3%) and 3/3 C4 (100%) with per patient and per segment specificity of 95.4% and 99.2%, respectively. CTC is an accurate technique to assess for significant synchronous lesions in patients with colorectal cancer and is applicable for total pre-operative colonic visualisation.

  18. Promoter Methylation Precedes Chromosomal Alterations in Colorectal Cancer Development

    Directory of Open Access Journals (Sweden)

    Sarah Derks

    2006-01-01

    Full Text Available Background: Colorectal cancers are characterized by genetic and epigenetic alterations. This study aimed to explore the timing of promoter methylation and relationship with mutations and chromosomal alterations in colorectal carcinogenesis. Methods: In a series of 47 nonprogressed adenomas, 41 progressed adenomas (malignant polyps, 38 colorectal carcinomas and 18 paired normal tissues, we evaluated promoter methylation status of hMLH1, O6MGMT, APC, p14ARF, p16INK4A, RASSF1A, GATA-4, GATA-5, and CHFR using methylation-specific PCR. Mutation status of TP53, APC and KRAS were studied by p53 immunohistochemistry and sequencing of the APC and KRAS mutation cluster regions. Chromosomal alterations were evaluated by comparative genomic hybridization. Results: Our data demonstrate that nonprogressed adenomas, progressed adenomas and carcinomas show similar frequencies of promoter methylation for the majority of the genes. Normal tissues showed significantly lower frequencies of promoter methylation of APC, p16INK4A, GATA-4, and GATA-5 (P-values: 0.02, 0.02, 1.1×10−5 and 0.008 respectively. P53 immunopositivity and chromosomal abnormalities occur predominantly in carcinomas (P values: 1.1×10−5 and 4.1×10−10. Conclusions: Since promoter methylation was already present in nonprogressed adenomas without chromosomal alterations, we conclude that promoter methylation can be regarded as an early event preceding TP53 mutation and chromosomal abnormalities in colorectal cancer development.

  19. A Gene Expression Classifier of Node-Positive Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Paul F. Meeh

    2009-10-01

    Full Text Available We used digital long serial analysis of gene expression to discover gene expression differences between node-negative and node-positive colorectal tumors and developed a multigene classifier able to discriminate between these two tumor types. We prepared and sequenced long serial analysis of gene expression libraries from one node-negative and one node-positive colorectal tumor, sequenced to a depth of 26,060 unique tags, and identified 262 tags significantly differentially expressed between these two tumors (P < 2 x 10-6. We confirmed the tag-to-gene assignments and differential expression of 31 genes by quantitative real-time polymerase chain reaction, 12 of which were elevated in the node-positive tumor. We analyzed the expression levels of these 12 upregulated genes in a validation panel of 23 additional tumors and developed an optimized seven-gene logistic regression classifier. The classifier discriminated between node-negative and node-positive tumors with 86% sensitivity and 80% specificity. Receiver operating characteristic analysis of the classifier revealed an area under the curve of 0.86. Experimental manipulation of the function of one classification gene, Fibronectin, caused profound effects on invasion and migration of colorectal cancer cells in vitro. These results suggest that the development of node-positive colorectal cancer occurs in part through elevated epithelial FN1 expression and suggest novel strategies for the diagnosis and treatment of advanced disease.

  20. The leptin gene family and colorectal cancer: interaction with smoking behavior and family history of cancer.

    Science.gov (United States)

    Liu, Li; Zhong, Rong; Wei, Sheng; Xiang, Hao; Chen, Jigui; Xie, Duoshuang; Yin, Jieyun; Zou, Li; Sun, Jingwen; Chen, Wei; Miao, Xiaoping; Nie, Shaofa

    2013-01-01

    Pathologic condition associated with metabolic syndrome traits seems to increase the risk of colorectal cancer. One mechanism underlying this relationship may involve the growth-promoting effects of the circulation hormones associated with obesity and insulin resistance, such as leptin. A two-stage case-control study was used to explore the role of polymorphisms of Leptin (LEP) and Leptin receptor (LEPR), either alone or in combination with environmental factors in colorectal carcinogenesis. In stage 1, 20 single nucleotide polymorphisms (SNPs) that tag common SNPs in these two genes were genotyped among 470 cases and 458 controls. In stage 2, another population with 314 cases and 355 controls were genotyped for the two most promising SNPs from stage 1. LEPR rs12037879 only presented modestly increased colorectal cancer risk, with odds ratios of 1.41 (95% confidence interval [CI] 1.13-1.76) and 1.74 (95%CI 1.08-2.81) for GA and AA genotype when compared with GG genotype in combined population. Smokers carrying LEPR rs12037879 A allele presented 1.67-fold (95%CI 1.39-fold to 2.01-fold) increased colorectal cancer risk when compared with non-smokers carrying GG genotype in combined analysis. Individuals with family history of cancer harboring LEPR rs12037879 A allele showed 1.52-fold (95%CI: 1.24-fold to 1.86-fold) increased colorectal cancer risk, compared with individuals without family history of cancer harboring GG genotype. Multifactor gene-environment interaction analysis revealed significant interactions among LEPR rs12037879, LEPR rs6690625, smoking status and family history of cancer, exhibiting a gradient of increased colorectal cancer risk along with the increasing number of risk factors (P = 9.82 × 10(-10)). Our research supports that polymorphisms in LEPR may be associated with marginal increase in the risk for colorectal cancer. Moreover, this association could be strengthened by cigarette smoking and family history of cancer.

  1. [Characteristics and Outcomes of Treatment in Patients with Stage IV Colorectal Cancer with Mismatch Repair Deficiency].

    Science.gov (United States)

    Ishibashi, Keiichiro; Chika, Noriyasu; Suzuki, Okihide; Ito, Tetsuya; Amano, Kunihiko; Kumamoto, Kensuke; Fukuchi, Minoru; Kumagai, Youichi; Mochiki, Erito; Ishida, Hideyuki

    2016-11-01

    Mismatch repair(MMR)protein deficiency in colorectal cancer is well correlated with high-level microsatellite instability (MSI-H). There are little data on mismatch repair deficiency(dMMR)colorectal cancers in Japan. In addition, we have no available data on the therapeutic efficacy of oxaliplatin(oxa)-based chemotherapy, one of the standard treatment regimens for metastatic colorectal cancer, for patients with dMMR colorectal cancer. The subjects were 254 patients with Stage IV colorectal cancer whose tumors were immunohistochemically stained for MMR proteins, MLH1, MSH2, MSH6, and PMS2. Patients who underwent R0 resection were excluded. Clinicopathologic factors and the efficacy of oxa-based chemotherapy were compared between patients with dMMR colorectal cancer and those with mismatch repair proficient(pMMR)colorectal cancer. There were 7(2.8%)patients with dMMR. Four patients demonstrated both MLH1 and PMS2 loss, while 3 patients demonstrated both MSH2 and MSH6 loss. Though the dMMR had a higher frequency in female patients(p=0.02) and a lower frequency in those with liver metastasis(pcolorectal cancers was lower than those(4-11%)reported in Western countries. Therefore, the clinical significance of universal screeningfor dMMR in all colorectal cancer samples may not be valid. Concerningsurvival benefit, oxa-based chemotherapy seems to be an effective alternative in clinical practice for metastatic colorectal cancer patients with dMMR.

  2. Relationship between Human Papilloma Virus and Colorectal Cancer in Northern Iran

    Directory of Open Access Journals (Sweden)

    Anahita Nosrati

    2015-10-01

    Full Text Available Background: Colorectal cancer is one of the most common malignancies worldwide with more than one million new cases. According to the Ministry of Health and Medical Education of Iran, colorectal cancer is the third most common cancer in Iran. Many risk factors are known causes of this disease. However, the molecular mechanisms associated with colorectal cancer are still under investigation. Recent studies have shown that some viruses, particularly human papilloma virus, may be associated with the pathology of colorectal cancer. Methods: This case-control study examined 95 colorectal cancer and 95 normal colon tissue paraffin blocks (control to identify the relationship between human papilloma virus and colorectal cancer by polymerase chain reaction. Results: Clinicopathological data that included sex, age, tumor grade, stage and location were recorded. All tumor and control groups (totally: 190 samples were negative in terms of the human papilloma virus genome. No relationship between clinicopathological data and human papilloma virus genome was identified. Conclusions: Regardless of other risk factors for colorectal cancer, a number of studies in different parts of the world have shown that human papilloma virus may be an important factor in the increasing incidence of colorectal cancer. However, we have found no association between human papilloma virus and colorectal cancer in this study.

  3. Association between documented family history of cancer and screening for breast and colorectal cancer.

    Science.gov (United States)

    Carney, Patricia A; O'Malley, Jean P; Gough, Andrea; Buckley, David I; Wallace, James; Fagnan, Lyle J; Morris, Cynthia; Mori, Motomi; Heintzman, John D; Lieberman, David

    2013-11-01

    Previous research on ascertainment of cancer family history and cancer screening has been conducted in urban settings. To examine whether documented family history of breast or colorectal cancer is associated with breast or colorectal cancer screening. Medical record reviews were conducted on 3433 patients aged 55 and older from four primary care practices in two rural Oregon communities. Data collected included patient demographic and risk information, including any documentation of family history of breast or colorectal cancer, and receipt of screening for these cancers. A positive breast cancer family history was associated with an increased likelihood of being up-to-date for mammography screening (OR 2.09, 95% CI 1.45-3.00 relative to a recorded negative history). A positive family history for colorectal cancer was associated with an increased likelihood of being up-to-date with colorectal cancer screening according to U.S. Preventive Services Task Force low risk guidelines for males (OR 2.89, 95% CI 1.15-7.29) and females (OR 2.47, 95% CI 1.32-4.64) relative to a recorded negative family history. The absence of any recorded family cancer history was associated with a decreased likelihood of being up-to-date for mammography screening (OR 0.70, 95% CI 0.56-0.88 relative to recorded negative history) or for colorectal cancer screening (OR 0.75, 95% CI 0.60-0.96 in females, OR 0.68, 95% CI 0.53-0.88 in males relative to recorded negative history). Further research is needed to determine if establishing routines to document family history of cancer would improve appropriate use of cancer screening. © 2013.

  4. CLINICAL CASE OF A MASSIVE ISOLA TED METASTATIC ADRENAL LESION IN COLORECT AL CANCER

    Directory of Open Access Journals (Sweden)

    I. P. Moshurov

    2015-01-01

    Full Text Available AbstractThe liver, lungs, parietal and visceral peritoneum have traditionally been considered to be the main target organs of metastatic colorectal cancer. The isolated adrenal metastasis in colorectal cancer is rare, in the literature there are single observations of clinical cases of successful surgical treatment of such patients. This article presents the clinical observation of successful surgical treatment of patients with colorectal cancer with massive isolated adrenal metastases.

  5. Classification of Dukes' B and C colorectal cancers using expression arrays

    DEFF Research Database (Denmark)

    Frederiksen, C.M.; Knudsen, Steen; Laurberg, S.

    2003-01-01

    Purpose. Colorectal cancer is one of the most common malignancies. Substaging of the cancer is of importance not only to prognosis but also to treatment. Classification of substages based on DNA microarray technology is currently the most promising approach. We therefore investigated if gene...... expression of one of the most common malignancies, colorectal cancer, now seems to be within reach. The data indicates that it is possible at least to classify Dukes' B and C colorectal tumors with microarrays....

  6. Intestinal stem cell imaging in colorectal cancer screening.

    Science.gov (United States)

    Moossavi, S; Ansari, R

    2013-01-01

    Colorectal cancer (CRC) is a common cancer and cause of cancer-related death worldwide. Although, the step-wise genetic alteration in the course of adenoma-carcinoma progression is well-understood, the mechanism of the tumour initiation and promotion is yet to be elucidated. Murine studies indicate that intestinal tumour originates from normal intestinal stem cells which acquire the oncogenic hits. It is plausible to consider the abnormality of the stem cell compartment as the earliest potentially detectable phenotypic change in the course of intestinal tumourigenesis. Hereby, it is hypothesised that imaging of the abnormal state of the intestinal stem cell compartment could potentially be integrated in CRC screening strategy.

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

    Directory of Open Access Journals (Sweden)

    Melany Cueva

    2013-08-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

  9. Demands of illness in people treated for colorectal cancer.

    Science.gov (United States)

    Klemm, P; Miller, M A; Fernsler, J

    2000-05-01

    To describe the most common and most intense demands of illness in people with colorectal cancer. Descriptive, comparative. People with colorectal cancer were accrued through weekly online computer postings. 121 people (68 men and 53 women) from 35 states (n = 106) and six other countries (n = 15) who were treated for colon, rectal, or anal cancer. Mailed questionnaires included a 125-item, self-report instrument with seven subscales (Demands of Illness Inventory (DOII) and a 14-item demographic form. Demands of illness, time since treatment, perception of illness state, activity level, and age. Demands of illness were greatest in the personal meaning domain, with more than 93% of subjects reporting that they thought about the value of life and how long they might live. More than 85% reported uncertainty in six similar areas. The 10 most intense demands were predominately psychosocial and existential concerns. Respondents in the youngest age group (illness, activity level) accounted for 45% of the variance in DOII scores. Colorectal cancer imposed significant psychosocial and existential concerns on respondents, especially the youngest age group. Nurses should address these concerns with patients while continuing to identify and scientifically test creative strategies to minimize psychosocial morbidity.

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

    Science.gov (United States)

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

    2016-05-01

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

  11. Discrepancies between estimated and perceived risk of cancer among individuals with hereditary nonpolyposis colorectal cancer

    DEFF Research Database (Denmark)

    Domanska, K; Nilbert, Mef; Soller, M

    2007-01-01

    Communicating cancer risk and recommending adequate control programs is central for genetic counseling. Individuals affected by hereditary nonpolyposis colorectal cancer (HNPCC) are at about 80% life-time risk of colorectal cancer and for female carriers 40-60% risk of endometrial cancer and 10...... to individual characteristics. A perceived risk of colorectal cancer above 60% was reported by 22/45 individuals, and only one out of five mutation carriers reported a perceived risk > 80%. Female mutation carriers, individuals below age 50, and individuals who received their oncogenetic counseling within 1...... and an increasing amount of data on the cancer risk in HNPCC, a minority of the mutation carriers report a perceived risk at the same level as that communicated during oncogenetic counseling....

  12. Awareness of endometrial cancer risk and compliance with screening in hereditary nonpolyposis colorectal cancer

    DEFF Research Database (Denmark)

    Ketabi, Zohreh; Mosgaard, Berit J; Gerdes, Anne-Marie

    2012-01-01

    Women with hereditary nonpolyposis colorectal cancer (HNPCC) have a 40-60% lifetime risk for endometrial cancer. Guidelines in Denmark recommend gynecologic screening for female members of families with HNPCC. We estimated the knowledge of endometrial cancer risk and identified possible predictors...

  13. Urinary tract cancer and hereditary nonpolyposis colorectal cancer : Risks and screening options

    NARCIS (Netherlands)

    Sijmons, RH; Kiemeney, LALM; Witjes, JA; Vasen, HFA

    Purpose: We investigate the risk of the different types of urinary tract cancer in hereditary nonpolyposis colorectal cancer families and review screening options. Materials and Methods: We retrospectively calculated the relative and cumulative risks of developing urinary tract cancer by comparing

  14. A novel transcript, VNN1-AB, as a biomarker for colorectal cancer.

    Science.gov (United States)

    Løvf, Marthe; Nome, Torfinn; Bruun, Jarle; Eknaes, Mette; Bakken, Anne C; Mpindi, John P; Kilpinen, Sami; Rognum, Torleiv O; Nesbakken, Arild; Kallioniemi, Olli; Lothe, Ragnhild A; Skotheim, Rolf I

    2014-11-01

    Colorectal cancer is a global health challenge with high incidence rate and mortality. The patients' prognosis is strongly associated with disease stage and currently there is a need for improved prognostic and predictive biomarkers. In this study, novel colorectal cancer-specific transcript structures were nominated from whole transcriptome sequencing of seven colorectal cancer cell lines, two primary colorectal carcinomas with corresponding normal colonic mucosa and 16 normal tissues. The nominated transcripts were combined with gene level outlier expression analyses in a cohort of 505 colorectal cancers to identify biomarkers with capacity to stratify colorectal cancer subgroups. The transcriptome sequencing data and outlier expression analysis revealed 11 novel colorectal cancer-specific exon-exon junctions, of which 3 were located in the gene VNN1. The junctions within VNN1 were further characterized using rapid amplification of cDNA ends (RACE) and the prevalence of the subsequently characterized novel transcript, VNN1-AB, was investigated by real-time RT-PCR in 291 samples of miscellaneous origins. VNN1-AB was not present in any of the 43 normal colorectal tissue samples investigated, but in 5 of the 6 polyps, and 102 of the 136 (75%) colorectal cancers. We have identified a novel transcript of the VNN1 gene, with an organ-confined complete specificity for colorectal neoplasia. © 2014 UICC.

  15. Most patients with colorectal tumors at young age do not visit a cancer genetics clinic.

    NARCIS (Netherlands)

    Overbeek, L.I.H.; Hoogerbrugge, N.; Krieken, J.H.J.M. van; Nagengast, F.M.; Ruers, T.J.M.; Ligtenberg, M.J.L.; Hermens, R.P.M.G.

    2008-01-01

    PURPOSE: This study examined the referral process for genetic counseling at a cancer genetics clinic in patients with colorectal cancer and to search for determinants of variation in this referral process. METHODS: Patients who were recently diagnosed with colorectal cancer at a young age or

  16. Prognostic significance of detection of microscopic peritoneal disease in colorectal cancer: a systematic review.

    LENUS (Irish Health Repository)

    Mohan, Helen M

    2013-06-01

    Free intraperitoneal tumour cells are an independent indicator of poor prognosis, and are encorporated in current staging systems in upper gastrointestinal cancers, but not colorectal cancer. This systematic review aimed to evaluate the role and prognostic significance of positive peritoneal lavage in colorectal cancer.

  17. Dietary calcium and phosphate in the prevention of colorectal cancer. Mechanism and nutrition implications

    NARCIS (Netherlands)

    Govers, Maria Johanna Adriana Petronella

    1993-01-01

    Colorectal cancer (cancerof the large intestine) is the second most common cause of cancer deaths in Western countries. Epidemiological studies suggest that environmental factors, and in particular dietary habits, play an important role in the etiology of colorectal cancer. A positive association

  18. Serum microRNA-135a-5p as an auxiliary diagnostic biomarker for colorectal cancer.

    Science.gov (United States)

    Wang, Qinjun; Zhang, Hongchun; Shen, Xianjuan; Ju, Shaoqing

    2017-01-01

    Objective The purpose of this study was to explore serum miR-135a-5p expression in colorectal cancer and examine the potential usefulness of this molecule as a biomarker for diagnosis in colorectal cancer. Methods Serum samples were collected from 60 patients with primary colorectal cancer, 40 patients with colorectal polyps and 50 healthy controls. Serum miR-135a-5p expression levels were detected by reverse transcription quantitative real-time quantitative polymerase chain reaction. Serum carcinoembryonic antigen and carbohydrate antigen 199 concentrations were detected by MODULAR ANALYTICS E170. Results The relative expression level of serum miR-135a-5p in colorectal cancer patients, colorectal polyps patients and healthy controls was 2.451 (1.107, 4.413), 0.946 (0.401, 1.942) and 0.949 (0.194, 1.415), respectively, indicating that it was significantly higher in colorectal cancer patients than that in the other two groups ( U = 351.0, 313.0, both P colorectal cancer patients. Compared with colorectal polyps group, AUCROC of serum miR-135a-5p in colorectal cancer group was 0.832 with 95% CI 0.73-0.93; compared with healthy control group, AUCROC was 0.875 with 95% CI 0.80-0.95. Conclusion Serum miR-135a-5p expression in colorectal cancer patients was higher than that in patients with colorectal polyps and healthy controls, suggesting that serum miR-135a-5p may prove to be an important biomarker for auxiliary diagnosis of colorectal cancer.

  19. 75 FR 2552 - NIH State-of-the-Science Conference: Enhancing Use and Quality of Colorectal Cancer Screening

    Science.gov (United States)

    2010-01-15

    ... Quality of Colorectal Cancer Screening Notice is hereby given by the National Institutes of Health (NIH... one type of polyp, known as an adenoma, can develop into colorectal cancer. Screening tests for... early cancer in people who have no symptoms. A range of colorectal cancer screening tests is available...

  20. Liver resection for colorectal cancer metastases

    Science.gov (United States)

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

    2013-01-01

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