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Sample records for colorectal xenografts influence

  1. Influence of histamine and serotonin antagonists on the growth of xenografted human colorectal tumors.

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    Barkla, D H; Tutton, P J

    1981-12-01

    Four lines of human colorectal cancer were established and serially propagated as subcutaneous xenographs in immunosuppressed inbred CBA/Lac mice. Established xenografts were then used to investigate the influence of a serotonin antagonist (BW 501c) and a histamine H2 receptor antagonists (Cimetidine) on xenograft growth. The growth of each of the four tumor lines was significantly inhibited by BW 501c throughout the treatment, whereas the growth of only two tumor lines was significantly inhibited by Cimetidine treatment. The response of individual tumor lines was not predictable on the basis of either tumor histopathology or the natural growth rate of the untreated xenograft. A number of alternative, but not mutually exclusive, hypotheses are suggested to explain the results. One hypothesis proposes that colorectal tumors are composed of subpopulations of tumor cells that are variously dependent on or independent of amine hormones. Another hypothesis is that tumor cells exhibit temporal changes in hormone sensitivity to amine hormones during treatment. Finally, it is suggested that serotonin and/or histamine H2 antagonists may be useful in preventing the repopulation of colorectal carcinomas following antineoplastic therapy with the use of conventional drugs.

  2. Age and cellular context influence rectal prolapse formation in mice with caecal wall colorectal cancer xenografts.

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    Tommelein, Joke; Gremonprez, Félix; Verset, Laurine; De Vlieghere, Elly; Wagemans, Glenn; Gespach, Christian; Boterberg, Tom; Demetter, Pieter; Ceelen, Wim; Bracke, Marc; De Wever, Olivier

    2016-11-15

    In patients with rectal prolapse is the prevalence of colorectal cancer increased, suggesting that a colorectal tumor may induce rectal prolapse. Establishment of tumor xenografts in immunodeficient mice after orthotopic inoculations of human colorectal cancer cells into the caecal wall is a widely used approach for the study of human colorectal cancer progression and preclinical evaluation of therapeutics. Remarkably, 70% of young mice carrying a COLO320DM caecal tumor showed symptoms of intussusception of the large bowel associated with intestinal lumen obstruction and rectal prolapse. The quantity of the COLO320DM bioluminescent signal of the first three weeks post-inoculation predicts prolapse in young mice. Rectal prolapse was not observed in adult mice carrying a COLO320DM caecal tumor or young mice carrying a HT29 caecal tumor. In contrast to HT29 tumors, which showed local invasion and metastasis, COLO320DM tumors demonstrated a non-invasive tumor with pushing borders without presence of metastasis. In conclusion, rectal prolapse can be linked to a non-invasive, space-occupying COLO320DM tumor in the gastrointestinal tract of young immunodeficient mice. These data reveal a model that can clarify the association of patients showing rectal prolapse with colorectal cancer.

  3. Cryopreservation of human colorectal carcinomas prior to xenografting

    International Nuclear Information System (INIS)

    Linnebacher, Michael; Maletzki, Claudia; Ostwald, Christiane; Klier, Ulrike; Krohn, Mathias; Klar, Ernst; Prall, Friedrich

    2010-01-01

    Molecular heterogeneity of colorectal carcinoma (CRC) is well recognized, forming the rationale for molecular tests required before administration of some of the novel targeted therapies that now are rapidly entering the clinics. For clinical research at least, but possibly even for future individualized tumor treatment on a routine basis, propagation of patients' CRC tissue may be highly desirable for detailed molecular, biochemical or functional analyses. However, complex logistics requiring close liaison between surgery, pathology, laboratory researchers and animal care facilities are a major drawback in this. We here describe and evaluate a very simple cryopreservation procedure for colorectal carcinoma tissue prior to xenografting that will considerably reduce this logistic complexity. Fourty-eight CRC collected ad hoc were xenografted subcutaneously into immunodeficient mice either fresh from surgery (N = 23) or after cryopreservation (N = 31; up to 643 days). Take rates after cryopreservation were satisfactory (71%) though somewhat lower than with tumor tissues fresh from surgery (74%), but this difference was not statistically significant. Re-transplantation of cryopreserved established xenografts (N = 11) was always successful. Of note, in this series, all of the major molecular types of CRC were xenografted successfully, even after cryopreservation. Our procedure facilitates collection, long-time storage and propagation of clinical CRC specimens (even from different centres) for (pre)clinical studies of novel therapies or for basic research

  4. Temporal morphologic changes in human colorectal carcinomas following xenografting.

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    Barkla, D H; Tutton, P J

    1983-03-01

    The temporal morphologic changes of human colorectal carcinomas following xenografting into immunosuppressed mice were investigated by the use of light and transmission electron microscopy. The results show that colorectal carcinomas undergo a series of morphologic changes during the initial 30-day period following transplantation. During the initial 1-5-day period the majority of tumor cells die, and during the following 5-10-day period the necrotic debris created during the 1-5-day period is removed by host-supplied inflammatory cells. Only small groups of peripherally placed tumor cells survived at the end of the first 10 days. During the 10-20-day period the tumor cell populations of xenografts were reestablished by a morphologically heterogeneous population of tumor cells, and during the 20-30 day period consolidation of this process continued and some xenografts showed macroscopic evidence of growth. The authors hypothesize that human colorectal carcinomas, like the antecedent epithelium, contain subpopulations of undifferentiated cells that give rise to populations of more-differentiated cells.

  5. Localization of radiolabeled anti-CEA antibody in subcutaneous and intrahepatic colorectal xenografts: influence of tumor size and location within host organ on antibody uptake

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    Dearling, Jason L.J. [Cancer Research UK Targeting and Imaging Group, Research Department of Oncology, UCL Cancer Institute, Paul O' Gorman Building, University College London, London WC1E 6BT (United Kingdom)], E-mail: j.dearling@hotmail.com; Flynn, Aiden A.; Qureshi, Uzma [Cancer Research UK Targeting and Imaging Group, Research Department of Oncology, UCL Cancer Institute, Paul O' Gorman Building, University College London, London WC1E 6BT (United Kingdom); Whiting, Stephen [Department of Clinical Biochemistry, Royal Free and University College Medical School, UCL, Royal Free Campus, London NW3 2PF (United Kingdom); Boxer, Geoffrey M.; Green, Alan; Begent, Richard H.J.; Pedley, R. Barbara [Cancer Research UK Targeting and Imaging Group, Research Department of Oncology, UCL Cancer Institute, Paul O' Gorman Building, University College London, London WC1E 6BT (United Kingdom)

    2009-11-15

    Introduction: Radioimmunotherapy (RIT) has been shown to be more effective against solid tumor micrometastases, possibly due to an inverse relationship between tumor size and radiolabeled antibody uptake. In this study, the accretion of radiolabeled antibody in intrahepatic micrometastases in an experimental model was investigated using quantitative digital autoradiography, enabling the analysis of antibody uptake in microscopic tumors. Methods: Mice bearing subcutaneous or intrahepatic metastatic models of LS174T colorectal cancer were injected with radiolabeled anti-carcinoembryonic antigen antibody ([{sup 125}I]A5B7). Tissues were taken to investigate distribution of radionuclide and tumor uptake. In a therapy study, mice bearing intrahepatic metastatic tumors were injected with [{sup 131}I]A5B7. Results: Subcutaneous tumors and large metastatic deposits had similar uptake (e.g., {approx}15%ID/g at 24 h). Small metastatic deposits had higher uptake (e.g., {approx}80%ID/g at 24 h) and prolonged retention at later time points. Small deposit uptake was significantly reduced by accompanying large deposits in the same liver. RIT resulted in increased survival time (untreated mean survival of 21.6{+-}12.9 vs. treated mean survival of 39.1{+-}30.8 days), but there was a large range of response within groups, presumably due to variation in pattern and extent of tumor as observed in the biodistribution study. Liver function tests and body weight did not change with tumor growth or therapy response, strongly supporting the use of in vivo imaging in metastatic tumor therapy studies. Conclusions: Radioimmunodetection and therapy might be greatly influenced by the size and distribution of intrahepatic tumor deposits.

  6. Localization of radiolabeled anti-CEA antibody in subcutaneous and intrahepatic colorectal xenografts: influence of tumor size and location within host organ on antibody uptake

    International Nuclear Information System (INIS)

    Dearling, Jason L.J.; Flynn, Aiden A.; Qureshi, Uzma; Whiting, Stephen; Boxer, Geoffrey M.; Green, Alan; Begent, Richard H.J.; Pedley, R. Barbara

    2009-01-01

    Introduction: Radioimmunotherapy (RIT) has been shown to be more effective against solid tumor micrometastases, possibly due to an inverse relationship between tumor size and radiolabeled antibody uptake. In this study, the accretion of radiolabeled antibody in intrahepatic micrometastases in an experimental model was investigated using quantitative digital autoradiography, enabling the analysis of antibody uptake in microscopic tumors. Methods: Mice bearing subcutaneous or intrahepatic metastatic models of LS174T colorectal cancer were injected with radiolabeled anti-carcinoembryonic antigen antibody ([ 125 I]A5B7). Tissues were taken to investigate distribution of radionuclide and tumor uptake. In a therapy study, mice bearing intrahepatic metastatic tumors were injected with [ 131 I]A5B7. Results: Subcutaneous tumors and large metastatic deposits had similar uptake (e.g., ∼15%ID/g at 24 h). Small metastatic deposits had higher uptake (e.g., ∼80%ID/g at 24 h) and prolonged retention at later time points. Small deposit uptake was significantly reduced by accompanying large deposits in the same liver. RIT resulted in increased survival time (untreated mean survival of 21.6±12.9 vs. treated mean survival of 39.1±30.8 days), but there was a large range of response within groups, presumably due to variation in pattern and extent of tumor as observed in the biodistribution study. Liver function tests and body weight did not change with tumor growth or therapy response, strongly supporting the use of in vivo imaging in metastatic tumor therapy studies. Conclusions: Radioimmunodetection and therapy might be greatly influenced by the size and distribution of intrahepatic tumor deposits.

  7. Colorectal cancer patient-derived xenografted tumors maintain characteristic features of the original tumors.

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    Cho, Yong Beom; Hong, Hye Kyung; Choi, Yoon-La; Oh, Ensel; Joo, Kyeung Min; Jin, Juyoun; Nam, Do-Hyun; Ko, Young-Hyeh; Lee, Woo Yong

    2014-04-01

    Despite significant improvements in colon cancer outcomes over the past few decades, preclinical development of more effective therapeutic strategies is still limited by the availability of clinically relevant animal models. To meet those clinical unmet needs, we generated a well-characterized in vivo preclinical platform for colorectal cancer using fresh surgical samples. Primary and metastatic colorectal tumor tissues (1-2 mm(3)) that originate from surgery were implanted into the subcutaneous space of nude mice and serially passaged in vivo. Mutation status, hematoxylin and eosin staining, short tandem repeat profiling, and array comparative genomic hybridization were used to validate the similarity of molecular characteristics between the patient tumors and tumors obtained from xenografts. From surgical specimens of 143 patients, 97 xenograft models were obtained in immunodeficient mice (establish rate = 67%). Thirty-nine xenograft models were serially expanded further in mice with a mean time to reach a size of 1000-1500 mm(3) of 90 ± 20 d. Histologic and immunohistochemical analyses revealed a high degree of pathologic similarity including histologic architecture and expression of CEA, CK7, and CD20 between the patient and xenograft tumors. Molecular analysis showed that genetic mutations, genomic alterations, and gene expression patterns of each patient tumor were also well conserved in the corresponding xenograft tumor. Xenograft animal models derived from fresh surgical sample maintained the key characteristic features of the original tumors, suggesting that this in vivo platform can be useful for preclinical development of novel therapeutic approaches to colorectal cancers. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Combining fisetin and ionizing radiation suppresses the growth of mammalian colorectal cancers in xenograft tumor models.

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    Leu, Jyh-Der; Wang, Bo-Shen; Chiu, Shu-Jun; Chang, Chun-Yuan; Chen, Chien-Chih; Chen, Fu-Du; Avirmed, Shiirevnyamba; Lee, Yi-Jang

    2016-12-01

    Fisetin (3,7,3',4'-tetrahydroxyflavone), which belongs to the flavonoid group of polyphenols and is found in a wide range of plants, has been reported to exhibit a number of biological activities in human cancer cells, including antioxidant, anti-inflammatory, antiangiogenic, anti-invasive and antiproliferative effects. Although previous in vitro studies have shown that fisetin treatment increases the apoptotic rate and enhances the radiosensitivity of human colorectal cancer cells, the in vivo effects of fisetin on tumor growth remain unclear. In the present study a murine xenograft tumor model was employed to investigate the therapeutic effects of fisetin in combination with radiation on CT-26 colon cancer cells and human HCT116 colorectal cancer cells. This revealed that intratumoral injection of fisetin significantly suppressed the growth of CT-26 tumors compared with the untreated control group, but had little effect on the growth of HCT116 tumors. However, fisetin in combination with 2-Gy radiation enhanced tumor suppressor activity in murine colon and human colorectal xenograft tumors, as compared with 2-Gy fractionated radiation administered alone for 5 days and fisetin alone. Interestingly, fisetin downregulated the expression of the oncoprotein securin in a p53-independent manner. However, securin-null HCT116 tumors showed only moderate sensitivity to fisetin treatment, and the combination of fisetin and radiation did not significantly suppress securin-null HCT116 tumor growth compared with normal HCT116 tumors. Therefore, the role of securin in mediating the effect of fisetin on colorectal cancer growth warrants further investigation. In conclusion, the results of the current study provide important preclinical data for evaluating the efficacy of fisetin and radiation combination treatment as an adjuvant chemoradiotherapy for human colorectal cancers.

  9. Influence of prostaglandin analogues on epithelial cell proliferation and xenograft growth.

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    Tutton, P J; Barkla, D H

    1980-01-01

    The influence of two prostaglandin (PG) analogues, 16,16-dimethyl PG E2 and 16,16-dimethyl PG F2 alpha and of the cyclo-oxygenase inhibitor, flurbiprofen, on epithelial cell proliferation was assessed using a stathmokinetic technique. The epithelia examined were those of the jejunal crypts, the colonic crypts and that of dimethylhydrazine-induced adenocarcinomas of rat colon. The influence of the two prostaglandin analogues, and of flurbiprofen, on the growth of a human colorectal tumour propagated as xenografts in immune-deprived mice was also assessed. The PG E2 analogue transiently inhibited xenograft growth, but was without effect on the mitotic rate in the rat tissues. The PG F2 alpha analogue was also found to inhibit xenograft growth but, unlike the PG E2 analogue, it was found to be a strong inhibitor of cell proliferation in rat colonic tumours, and an accelerator of proliferation in jejunal-crypt cells. The only statistically significant effect of flurbiprofen was to accelerate cell division in the rat colonic tumours.

  10. Combination of Vandetanib, Radiotherapy, and Irinotecan in the LoVo Human Colorectal Cancer Xenograft Model

    International Nuclear Information System (INIS)

    Wachsberger, Phyllis; Burd, Randy; Ryan, Anderson; Daskalakis, Constantine; Dicker, Adam P.

    2009-01-01

    Purpose: The tumor growth kinetics of the human LoVo colorectal xenograft model was assessed in response to vandetanib, an orally available receptor tyrosine kinase inhibitor, radiotherapy (RT), or irinotecan (CPT-11), as single therapies and in combination. Methods and Materials: LoVo cells were injected subcutaneously into the right hind limb (5x10 6 cells in 100μL phosphate-buffered saline) of athymic NCR NUM mice and tumors were grown to a volume of 200-300 mm 3 before treatment. Vandetanib was administered at 50 mg/kg daily orally for 14 days starting on Day 1. RT was given as three fractions (3x3 Gy) on Days 1, 2, and 3. CPT-11 was given at 15 mg/kg intraperitoneally on Days 1 and 3. Tumor volumes were measured on a daily basis and calculated by measuring tumor diameters with digital calipers in two orthogonal dimensions. Results: All three single treatments (vandetanib, CPT-11, and radiation) significantly slowed LoVo colorectal tumor growth. Vandetanib significantly increased the antitumor effects of CPT-11 and radiation when given in combination with either of these treatments. These treatment combinations resulted in a slow tumor growth rate during the 2 weeks of vandetanib administration. The triple combination of vandetanib, CPT-11, and radiation produced the most marked improvement in response as observed by measurable shrinkage of tumors during the first week of treatment. Conclusions: The tumor growth delay kinetics observed in this study of the LoVo colorectal model suggest concurrent and sustained post-sequencing of vandetanib with cytotoxic therapy may be beneficial in tumors of this type.

  11. [Compound K suppresses myeloid-derived suppressor cells in a mouse model bearing CT26 colorectal cancer xenograft].

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    Wang, Rong; Li, Yalin; Wang, Wuzhou; Zhou, Meijuan; Cao, Zhaohui

    2015-05-01

    To investigate the effect of ginseng-derived compound K (C-K) on apoptosis, immunosuppressive activity, and pro-inflammatory cytokine production of myeloid-derived suppressor cells (MDSCs) from mice bearing colorectal cancer xenograft. Flow-sorted bone marrow MDSCs from Balb/c mice bearing CT26 tumor xenograft were treated with either C-K or PBS for 96 h and examined for apoptosis with Annexin V/7-AAD, Cox-2 and Arg-1 expressions using qRT-PCR, and supernatant IL-1β, IL-6, and IL-17 levels with ELISA. C-K- or PBS-treated MDSCs were subcutaneously implanted along with CT26 tumor cells in WT Balb/c mice, and the tumor size and morphology were evaluated 21 days later. C-K treatment significantly increased the percentages of early and late apoptotic MDSCs in vitro (Pimmunosuppresive effect of MDSCs to inhibit tumor cell proliferation in mice, which suggests a new strategy of tumor therapy by targeting MDSCs.

  12. Combining fisetin and ionizing radiation suppresses the growth of mammalian colorectal cancers in xenograft tumor models

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    Leu, Jyh-Der; Wang, Bo-Shen; Chiu, Shu-Jun; Chang, Chun-Yuan; Chen, Chien-Chih; Chen, Fu-Du; Avirmed, Shiirevnyamba; Lee, Yi-Jang

    2016-01-01

    Fisetin (3,7,3?,4?-tetrahydroxyflavone), which belongs to the flavonoid group of polyphenols and is found in a wide range of plants, has been reported to exhibit a number of biological activities in human cancer cells, including antioxidant, anti-inflammatory, antiangiogenic, anti-invasive and antiproliferative effects. Although previous in vitro studies have shown that fisetin treatment increases the apoptotic rate and enhances the radiosensitivity of human colorectal cancer cells, the in vi...

  13. Enhanced antitumor efficacy and reduced systemic toxicity of sulfatide-containing nanoliposomal doxorubicin in a xenograft model of colorectal cancer.

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    Jia Lin

    Full Text Available Sulfatide is a glycosphingolipid known to interact with several extracellular matrix proteins, such as tenascin-C which is overexpressed in many types of cancer including that of the colon. In view of the limited success of chemotherapy in colorectal cancer and high toxicity of doxorubicin (DOX, a sulfatide-containing liposome (SCL encapsulation approach was taken to overcome these barriers. This study assessed the in vitro cytotoxicity, biodistribution, therapeutic efficacy and systemic toxicity in vivo of sulfatide-containing liposomal doxorubicin (SCL-DOX using human colonic adenocarcinoma HT-29 xenograft as the experimental model. In vitro, SCL-DOX was shown to be delivered into the nuclei and displayed prolonged retention compared with the free DOX. The use of this nanodrug delivery system to deliver DOX for treatment of tumor-bearing mice produced a much improved therapeutic efficacy in terms of tumor growth suppression and extended survival in contrast to the free drug. Furthermore, treatment of tumor-bearing mice with SCL-DOX resulted in a lower DOX uptake in the principal sites of toxicity of the free drug, namely the heart and skin, as well as reduced myelosuppression and diminished cardiotoxicity. Such natural lipid-guided nanodrug delivery systems may represent a new strategy for the development of effective anticancer chemotherapeutics targeting the tumor microenvironment for both primary tumor and micrometastases.

  14. Imaging of dihydrofolate reductase fusion gene expression in xenografts of human liver metastases of colorectal cancer in living rats

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    Mayer-Kuckuk, Philipp; Bertino, Joseph R.; Banerjee, Debabrata [Molecular Pharmacology and Therapeutics Program, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); The Cancer Institute of New Jersey, Robert Wood Johnson Medical School/UMDNJ, 195 Little Albany Street, NJ 08903, New Brunswick (United States); Doubrovin, Mikhail; Blasberg, Ronald; Tjuvajev, Juri Gelovani [Department of Neurooncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Gusani, Niraj J.; Fong, Yuman [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Gade, Terence; Koutcher, Jason A. [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Balatoni, Julius; Finn, Ronald [Radiochemistry/Cyclotron Core Facility, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Akhurst, Tim; Larson, Steven [Nuclear Medicine Service, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)

    2003-09-01

    Radionuclide imaging has been demonstrated to be feasible to monitor transgene expression in vivo. We hypothesized that a potential application of this technique is to non-invasively detect in deep tissue, such as cancer cells metastatic to the liver, a specific molecular response following systemic drug treatment. Utilizing human colon adenocarcinoma cells derived from a patient's liver lesion we first developed a nude rat xenograft model for colorectal cancer metastatic to the liver. Expression of a dihydrofolate reductase-herpes simplex virus 1 thymidine kinase fusion (DHFR-HSV1 TK) transgene in the hepatic tumors was monitored in individual animals using the tracer [{sup 124}I]2'-fluoro-2'-deoxy-5-iodouracil-{beta}-d-arabinofuranoside (FIAU) and a small animal micro positron emission tomograph (microPET), while groups of rats were imaged using the tracer [{sup 131}I]FIAU and a clinical gamma camera. Growth of the human metastatic colorectal cancer cells in the rat liver was detected using magnetic resonance imaging and confirmed by surgical inspection. Single as well as multiple lesions of different sizes and sites were observed in the liver of the animals. Next, using a subset of rats bearing hepatic tumors, which were retrovirally bulk transduced to express the DHFR-HSV1 TK transgene, we imaged the fusion protein expression in the hepatic tumor of living rats using the tracer [{sup 124}I]FIAU and a microPET. The observed deep tissue signals were highly specific for the tumors expressing the DHFR-HSV1 TK fusion protein compared with parental untransduced tumors and other tissues as determined by gamma counting of tissue samples. A subsequent study used the tracer [{sup 131}I]FIAU and a gamma camera to monitor two groups of transduced hepatic tumor-bearing rats. Prior to imaging, one group was treated with trimetrexate to exploit DHFR-mediated upregulation of the fusion gene product. Imaging in the living animal as well as subsequent gamma

  15. Combined 5-FU and ChoKα inhibitors as a new alternative therapy of colorectal cancer: evidence in human tumor-derived cell lines and mouse xenografts.

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    Ana de la Cueva

    Full Text Available Colorectal cancer (CRC is the third major cause of cancer related deaths in the world. 5-fluorouracil (5-FU is widely used for the treatment of colorectal cancer but as a single-agent renders low response rates. Choline kinase alpha (ChoKα, an enzyme that plays a role in cell proliferation and transformation, has been reported overexpressed in many different tumors, including colorectal tumors. ChoKα inhibitors have recently entered clinical trials as a novel antitumor strategy.ChoKα specific inhibitors, MN58b and TCD-717, have demonstrated a potent antitumoral activity both in vitro and in vivo against several tumor-derived cell line xenografts including CRC-derived cell lines. The effect of ChoKα inhibitors in combination with 5-FU as a new alternative for the treatment of colon tumors has been investigated both in vitro in CRC-tumour derived cell lines, and in vivo in mouse xenografts models. The effects on thymidilate synthase (TS and thymidine kinase (TK1 levels, two enzymes known to play an essential role in the mechanism of action of 5-FU, were analyzed by western blotting and quantitative PCR analysis. The combination of 5-FU with ChoKα inhibitors resulted in a synergistic effect in vitro in three different human colon cancer cell lines, and in vivo against human colon xenografts in nude mice. ChoKα inhibitors modulate the expression levels of TS and TK1 through inhibition of E2F production, providing a rational for its mechanism of action.Our data suggest that both drugs in combination display a synergistic antitumoral effect due to ChoKα inhibitors-driven modulation of the metabolization of 5-FU. The clinical relevance of these findings is strongly supported since TCD-717 has recently entered Phase I clinical trials against solid tumors.

  16. New peptide receptor radionuclide therapy of invasive cancer cells: in vivo studies using 177Lu-DOTA-AE105 targeting uPAR in human colorectal cancer xenografts

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    Persson, Morten; Rasmussen, Palle; Madsen, Jacob

    2012-01-01

    -of-concept for a theranostic approach as treatment modality in a human xenograft colorectal cancer model. MethodsA DOTA-conjugated 9-mer high affinity uPAR binding peptide (DOTA-AE105) was radiolabeled with 64Cu and 177Lu, for PET imaging and targeted radionuclide therapy study, respectively. Human uPAR-positive CRC HT-29...... for the first time the in vivo efficacy of an uPAR-targeted radionuclide therapeutic intervention on both tumor size and its content of uPAR expressing cells thus setting the stage for future translation into clinical use. © 2012 Elsevier Inc. All rights reserved....

  17. Preclinical In Vitro and In Vivo Evaluation of [18F]FE@SUPPY for Cancer PET Imaging: Limitations of a Xenograft Model for Colorectal Cancer

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    T. Balber

    2018-01-01

    Full Text Available Molecular imaging probes such as PET-tracers have the potential to improve the accuracy of tumor characterization by directly visualizing the biochemical situation. Thus, molecular changes can be detected early before morphological manifestation. The A3 adenosine receptor (A3AR is described to be highly expressed in colon cancer cell lines and human colorectal cancer (CRC, suggesting this receptor as a tumor marker. The aim of this preclinical study was the evaluation of F18FE@SUPPY as a PET-tracer for CRC using in vitro imaging and in vivo PET imaging. First, affinity and selectivity of FE@SUPPY and its metabolites were determined, proving the favorable binding profile of FE@SUPPY. The human adenocarcinoma cell line HT-29 was characterized regarding its hA3AR expression and was subsequently chosen as tumor graft. Promising results regarding the potential of F18FE@SUPPY as a PET-tracer for CRC imaging were obtained by autoradiography as ≥2.3-fold higher accumulation of F18FE@SUPPY was found in CRC tissue compared to adjacent healthy colon tissue from the same patient. Nevertheless, first in vivo studies using HT-29 xenografts showed insufficient tumor uptake due to (1 poor conservation of target expression in xenografts and (2 unfavorable pharmacokinetics of F18FE@SUPPY in mice. We therefore conclude that HT-29 xenografts are not adequate to visualize hA3ARs using F18FE@SUPPY.

  18. Factors Influencing Colorectal Cancer Screening Participation

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    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.

  19. Radiosensitivity of four human tumor xenografts. Influence of hypoxia and cell-cell contact

    International Nuclear Information System (INIS)

    Guichard, M.; Dertinger, H.; Malaise, E.P.

    1983-01-01

    Contact effect (CE) and hypoxia have been studied in human tumor cell lines transplanted in athymic nude mice. Four cell lines - one melanoma (Bell) and three colorectal adenocarcinomas (HT29, HRT18, and HCT8) - were studied. Cell survival was determined with an in vivo in vitro colony-forming assay. Survival curves were obtained under three different conditions: (1) tumor cells irradiated in air-breathing mice, (2) tumor cells irradiated in animals asphyxiated for 10 min, and (3) tumor cells plated and irradiated either immediately or 5 hr later. For all cell lines, radiosensitivity appeared to be lower when cells were irradiated in vivo than when they were irradiated in vitro. Only in the case of the HCT8 tumor did the relative in vivo radioresistance seem to be linked to hypoxia; in the other cell lines, hypoxia alone could not account for the lower in vivo radiosensitivity. Our results suggest that a CE plays an important role in the response of human xenografts to irradiation

  20. 64Cu-ATSM Reflects pO2 Levels in Human Head and Neck Cancer Xenografts but Not in Colorectal Cancer Xenografts: Comparison with 64CuCl2.

    Science.gov (United States)

    Li, Fan; Jørgensen, Jesper T; Forman, Julie; Hansen, Anders E; Kjaer, Andreas

    2016-03-01

    The hypoxia PET tracer (64)Cu-diacetyl-bis(N(4)-methylthiosemicarbazonate) ((64)Cu-ATSM) has shown promising results in clinical studies. However, concerns have been raised with regard to the possible effect of copper metabolism and free copper on tumor uptake and thereby the robustness of (64)Cu-ATSM as a hypoxia marker. In this study, accumulation and distribution of (64)Cu-ATSM and (64)CuCl2 in tumor tissue were compared with partial pressure of oxygen (pO2) probe measurements. One-hour dynamic PET scans were performed on nude mice bearing subcutaneous human head and neck tumors (FaDu) and human colorectal tumors (HT29) after administration of either (64)Cu-ATSM or (64)CuCl2. Subsequently, tracks were generated and track markers were positioned in tumors to allow for registration of their exact location on the high-resolution CT scan. After completion of the CT scan, pO2 probe measurements were performed along each track. PET and CT images were coregistered and ROIs drawn on the basis of the location of track markers and pO2 probe measurement depth. A linear mixed model for repeated measures was applied for the comparison of PET tracer uptake to corresponding pO2 values. Comparable uptake of (64)Cu-ATSM and (64)CuCl2 was found in the kidney, muscle, and liver of all animals, but (64)CuCl2 showed a higher uptake 10-60 min after injection in both tumor models. Significant differences were also found for both tumor-to-muscle and tumor-to-liver ratios. The intratumoral distribution of (64)Cu-ATSM, but not (64)CuCl2, showed a significant negative relationship with pO2 measurements in FaDu tumors. However, this relationship was not found in HT29 tumors. (64)Cu-ATSM and (64)CuCl2 displayed different uptake in tumors. In human head and neck xenografts, (64)Cu-ATSM but not (64)CuCl2 reflected pO2 measurements, indicating that (64)Cu-ATSM is a hypoxia-specific marker in this tumor type. However, data from colorectal cancer xenografts indicated that (64)Cu-ATSM may not be

  1. New peptide receptor radionuclide therapy of invasive cancer cells: in vivo studies using 177Lu-DOTA-AE105 targeting uPAR in human colorectal cancer xenografts

    International Nuclear Information System (INIS)

    Persson, Morten; Rasmussen, Palle; Madsen, Jacob; Ploug, Michael; Kjaer, Andreas

    2012-01-01

    The proposition of uPAR as a potential target in cancer therapy is advanced by its predominant expression at the invasive front of colorectal cancer (CRC) and its value as prognostic biomarker for poor survival in this disease. In this study, we provide the first in vivo proof-of-concept for a theranostic approach as treatment modality in a human xenograft colorectal cancer model. Methods: A DOTA-conjugated 9-mer high affinity uPAR binding peptide (DOTA-AE105) was radiolabeled with 64 Cu and 177 Lu, for PET imaging and targeted radionuclide therapy study, respectively. Human uPAR-positive CRC HT-29 cells were inoculated in Nude mice and treated with 177 Lu-DOTA-AE105 once a visible tumor had formed. To evaluate the true effect of the targeted radiotherapy, two controls groups were included in this study, one receiving a 177 Lu-labeled non-binding control peptide and one receiving vehicle. All animals were treated day 0 and 7. A parallel 18 F-FLT PET/CT study was performed on day 0, 1, 3 and 6. Dosimetry calculations were based on a biodistribution study, where organs and tissue of interest were collected 0.5, 1.0, 2.0, 4.0 and 24 h post injection of 177 Lu-DOTA-AE105. Toxicity was assessed by recording mouse weight and by H and E staining of kidneys in each treatment group. Results: uPAR-positive HT-29 xenograft was clearly visualized by PET/CT imaging using 64 Cu-DOTA-AE105. Subsequently, these xenograft transplants were locally irradiated using 177 Lu-DOTA-AE105, where a significant effect on tumor size and the number of uPAR-positive cells in the tumor was found (p 18 F-FLT PET/CT imaging study revealed a significant correlation between 18 F-FLT tumor uptake and efficacy of the radionuclide therapy. A histological examination of the kidneys from one animal in each treatment group did not reveal any gross abnormalities and the general performance of all treated animals also showed no indications of radioactivity-induced toxicity. Conclusion: These findings

  2. Expression of adrenomedullin in human colorectal tumors and its role in cell growth and invasion in vitro and in xenograft growth in vivo

    International Nuclear Information System (INIS)

    Nouguerède, Emilie; Berenguer, Caroline; Garcia, Stéphane; Bennani, Bahia; Delfino, Christine; Nanni, Isabelle; Dahan, Laetitia; Gasmi, Mohamed; Seitz, Jean-François; Martin, Pierre-Marie; Ouafik, L'Houcine

    2013-01-01

    Adrenomedullin (AM) is a multifunctional peptide vasodilator that transduces its effects through calcitonin receptor-like receptor/receptor activity-modifying protein-2 and -3 (CLR/RAMP2 and CLR/RAMP3). In this study, real-time quantitative reverse transcription demonstrated a significant expression of AM mRNA in tumor samples from colorectal cancer (CRC) patients in clinical stage II, III, and IV when compared with normal colorectal tissue. AM, CLR, RAMP2, and RAMP3 proteins were immunohistochemically localized in the carcinomatous epithelial compartment of CRC tissue. Tissue microarray analysis revealed a clear increase of AM, CLR, RAMP2, and RAMP3 staining in lymph node and distant metastasis when compared with primary tumors. The human colon carcinoma cells HT-29 expressed and secreted AM into the culture medium with a significant increase under hypoxia. Treatment of HT-29 cells with synthetic AM stimulated cell proliferation and invasion in vitro. Incubation with anti-AM antibody (αAM), anti-AM receptors antibodies (αAMR), or AM antagonist AM 22–52 inhibited significantly basal levels of proliferation of HT-29 cells, suggesting that AM may function as an autocrine growth factor for CRC cells. Treatment with αAM significantly suppressed the growth of HT-29 tumor xenografts in vivo. Histological examination of αAM-treated tumors showed evidence of disruption of tumor vascularity with decreased microvessel density, depletion of endothelial cells and pericytes, and increased tumor cell apoptosis. These findings highlight the potential importance of AM and its receptors in the progression of CRC and support the conclusion that αAM treatment inhibits tumor growth by suppression of angiogenesis and tumor growth, suggesting that AM may be a useful therapeutic target

  3. KRAS exon 2 mutations influence activity of regorafenib in an SW48-based disease model of colorectal cancer.

    Science.gov (United States)

    Camaj, Peter; Primo, Stefano; Wang, Yan; Heinemann, Volker; Zhao, Yue; Laubender, Ruediger Paul; Stintzing, Sebastian; Giessen-Jung, Clemens; Jung, Andreas; Gamba, Sebastian; Bruns, Christiane Josephine; Modest, Dominik Paul

    2015-01-01

    To investigate the impact of KRAS mutation variants on the activity of regorafenib in SW48 colorectal cancer cells. Activity of regorafenib was evaluated in isogenic SW48 KRAS wild-type (WT) and mutant cells. Subcutaneous xenografts (KRAS WT and G12C mutant variants) in NOD/SCID mice were analyzed to elucidate the effect of regorafenib treatment in vivo. Compared with KRAS WT cells, all mutant variants seemed associated with some degree of resistance to regorafenib-treatment in vitro. In vivo, activation of apoptosis (TUNEL) and reduction of proliferation (Ki67) after treatment with regorafenib were more pronounced in KRAS WT tumors as compared with G12C variants. In SW48 cells, exon 2 mutations of the KRAS gene may influence antitumor effects of regorafenib.

  4. The COLON study: Colorectal cancer: Longitudinal, Observational study on Nutritional and lifestyle factors that may influence colorectal tumour recurrence, survival and quality of life

    OpenAIRE

    Winkels, R.M.; Heine-Bröring, R.C.; Zutphen, van, M.; Harten-Gerritsen, van, A.S.; Kok, D.E.G.; Duijnhoven, van, F.J.B.; Kampman, E.

    2014-01-01

    BACKGROUND: There is clear evidence that nutrition and lifestyle can modify colorectal cancer risk. However, it is not clear if those factors can affect colorectal cancer treatment, recurrence, survival and quality of life. This paper describes the background and design of the "COlorectal cancer: Longitudinal, Observational study on Nutritional and lifestyle factors that may influence colorectal tumour recurrence, survival and quality of life" - COLON - study. The main aim of this study is to...

  5. Antitumor Efficacy of the Dual PI3K/mTOR Inhibitor PF-04691502 in a Human Xenograft Tumor Model Derived from Colorectal Cancer Stem Cells Harboring a PIK3CA Mutation.

    Directory of Open Access Journals (Sweden)

    Douglas D Fang

    Full Text Available PIK3CA (phosphoinositide-3-kinase, catalytic, alpha polypeptide mutations can help predict the antitumor activity of phosphatidylinositol-3-kinase (PI3K/mammalian target of rapamycin (mTOR pathway inhibitors in both preclinical and clinical settings. In light of the recent discovery of tumor-initiating cancer stem cells (CSCs in various tumor types, we developed an in vitro CSC model from xenograft tumors established in mice from a colorectal cancer patient tumor in which the CD133+/EpCAM+ population represented tumor-initiating cells. CD133+/EpCAM+ CSCs were enriched under stem cell culture conditions and formed 3-dimensional tumor spheroids. Tumor spheroid cells exhibited CSC properties, including the capability for differentiation and self-renewal, higher tumorigenic potential and chemo-resistance. Genetic analysis using an OncoCarta™ panel revealed a PIK3CA (H1047R mutation in these cells. Using a dual PI3K/mTOR inhibitor, PF-04691502, we then showed that blockage of the PI3K/mTOR pathway inhibited the in vitro proliferation of CSCs and in vivo xenograft tumor growth with manageable toxicity. Tumor growth inhibition in mice was accompanied by a significant reduction of phosphorylated Akt (pAKT (S473, a well-established surrogate biomarker of PI3K/mTOR signaling pathway inhibition. Collectively, our data suggest that PF-04691502 exhibits potent anticancer activity in colorectal cancer by targeting both PIK3CA (H1047R mutant CSCs and their derivatives. These results may assist in the clinical development of PF-04691502 for the treatment of a subpopulation of colorectal cancer patients with poor outcomes.

  6. Theranostic pretargeted radioimmunotherapy of colorectal cancer xenografts in mice using picomolar affinity {sup 86}Y- or {sup 177}Lu-DOTA-Bn binding scFv C825/GPA33 IgG bispecific immunoconjugates

    Energy Technology Data Exchange (ETDEWEB)

    Cheal, Sarah M.; Lee, Sang-gyu; Punzalan, Blesida; Larson, Steven M. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Memorial Sloan Kettering Cancer Center, Molecular Pharmacology and Chemistry Program, New York, NY (United States); Xu, Hong; Guo, Hong-fen [Memorial Sloan Kettering Cancer Center, Department of Pediatrics, New York, NY (United States); Chalasani, Sandhya; Carrasquillo, Jorge A. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Fung, Edward K. [Memorial Sloan Kettering Cancer Center, Molecular Pharmacology and Chemistry Program, New York, NY (United States); Memorial Sloan Kettering Cancer Center, Department of Medical Physics, New York, NY (United States); Jungbluth, Achim [Memorial Sloan Kettering Cancer Center, Department of Pathology, New York, NY (United States); Zanzonico, Pat B.; O' Donoghue, Joseph [Memorial Sloan Kettering Cancer Center, Department of Medical Physics, New York, NY (United States); Smith-Jones, Peter M. [Stony Brook University, Department of Psychiatry and Behavioral Science, Stony Brook, NY (United States); Stony Brook University, Department of Radiology, Stony Brook, NY (United States); Wittrup, K.D. [Massachusetts Institute of Technology, Department of Chemical Engineering, Cambridge, MA (United States); Massachusetts Institute of Technology, Department of Biological Engineering, Cambridge, MA (United States); Massachusetts Institute of Technology, Koch Institute for Integrative Cancer Research, Cambridge, MA (United States); Cheung, Nai-Kong V. [Memorial Sloan Kettering Cancer Center, Molecular Pharmacology and Chemistry Program, New York, NY (United States); Memorial Sloan Kettering Cancer Center, Department of Pediatrics, New York, NY (United States)

    2016-05-15

    GPA33 is a colorectal cancer (CRC) antigen with unique retention properties after huA33-mediated tumor targeting. We tested a pretargeted radioimmunotherapy (PRIT) approach for CRC using a tetravalent bispecific antibody with dual specificity for GPA33 tumor antigen and DOTA-Bn-(radiolanthanide metal) complex. PRIT was optimized in vivo by titrating sequential intravenous doses of huA33-C825, the dextran-based clearing agent, and the C825 haptens {sup 177}Lu-or {sup 86}Y-DOTA-Bn in mice bearing the SW1222 subcutaneous (s.c.) CRC xenograft model. Using optimized PRIT, therapeutic indices (TIs) for tumor radiation-absorbed dose of 73 (tumor/blood) and 12 (tumor/kidney) were achieved. Estimated absorbed doses (cGy/MBq) to tumor, blood, liver, spleen, and kidney for single-cycle PRIT were 65.8, 0.9 (TI 73), 6.3 (TI 10), 6.6 (TI 10), and 5.3 (TI 12), respectively. Two cycles of PRIT (66.6 or 111 MBq {sup 177}Lu-DOTA-Bn) were safe and effective, with a complete response of established s.c. tumors (100 - 700 mm{sup 3}) in nine of nine mice, with two mice alive without recurrence at >140 days. Tumor log kill in this model was estimated to be 2.1 - 3.0 based on time to 500-mm{sup 3} tumor recurrence. In addition, PRIT dosimetry/diagnosis was performed by PET imaging of the positron-emitting DOTA hapten {sup 86}Y-DOTA-Bn. We have developed anti-GPA33 PRIT as a triple-step theranostic strategy for preclinical detection, dosimetry, and safe targeted radiotherapy of established human colorectal mouse xenografts. (orig.)

  7. Theranostic pretargeted radioimmunotherapy of colorectal cancer xenografts in mice using picomolar affinity 86Y- or 177Lu-DOTA-Bn binding scFv C825/GPA33 IgG bispecific immunoconjugates

    International Nuclear Information System (INIS)

    Cheal, Sarah M.; Lee, Sang-gyu; Punzalan, Blesida; Larson, Steven M.; Xu, Hong; Guo, Hong-fen; Chalasani, Sandhya; Carrasquillo, Jorge A.; Fung, Edward K.; Jungbluth, Achim; Zanzonico, Pat B.; O'Donoghue, Joseph; Smith-Jones, Peter M.; Wittrup, K.D.; Cheung, Nai-Kong V.

    2016-01-01

    GPA33 is a colorectal cancer (CRC) antigen with unique retention properties after huA33-mediated tumor targeting. We tested a pretargeted radioimmunotherapy (PRIT) approach for CRC using a tetravalent bispecific antibody with dual specificity for GPA33 tumor antigen and DOTA-Bn-(radiolanthanide metal) complex. PRIT was optimized in vivo by titrating sequential intravenous doses of huA33-C825, the dextran-based clearing agent, and the C825 haptens 177 Lu-or 86 Y-DOTA-Bn in mice bearing the SW1222 subcutaneous (s.c.) CRC xenograft model. Using optimized PRIT, therapeutic indices (TIs) for tumor radiation-absorbed dose of 73 (tumor/blood) and 12 (tumor/kidney) were achieved. Estimated absorbed doses (cGy/MBq) to tumor, blood, liver, spleen, and kidney for single-cycle PRIT were 65.8, 0.9 (TI 73), 6.3 (TI 10), 6.6 (TI 10), and 5.3 (TI 12), respectively. Two cycles of PRIT (66.6 or 111 MBq 177 Lu-DOTA-Bn) were safe and effective, with a complete response of established s.c. tumors (100 - 700 mm 3 ) in nine of nine mice, with two mice alive without recurrence at >140 days. Tumor log kill in this model was estimated to be 2.1 - 3.0 based on time to 500-mm 3 tumor recurrence. In addition, PRIT dosimetry/diagnosis was performed by PET imaging of the positron-emitting DOTA hapten 86 Y-DOTA-Bn. We have developed anti-GPA33 PRIT as a triple-step theranostic strategy for preclinical detection, dosimetry, and safe targeted radiotherapy of established human colorectal mouse xenografts. (orig.)

  8. Theranostic pretargeted radioimmunotherapy of colorectal cancer xenografts in mice using picomolar affinity Y-86- or Lu-177-DOTA-Bn binding scFv C825/GPA33 IgG bispecific immunoconjugates

    Science.gov (United States)

    Cheal, Sarah M.; Xu, Hong; Guo, Hong-fen; Lee, Sang-gyu; Punzalan, Blesida; Chalasani, Sandhya; Fung, Edward K.; Jungbluth, Achim; Zanzonico, Pat B.; Carrasquillo, Jorge A.; O’Donoghue, Joseph; Smith-Jones, Peter M.; Wittrup, K. Dane; Cheung, Nai-Kong V.; Larson, Steven M.

    2015-01-01

    Purpose GPA33 is a colorectal cancer (CRC) antigen with unique retention properties after huA33-mediated tumor targeting. We tested a pre-targeted radioimmunotherapy (PRIT) approach for CRC using a tetravalent bispecific antibody with dual specificity for GPA33 tumor antigen and DOTA-Bn (radiolanthanide metal) complex. Methods PRIT was optimized in vivo by titrating sequential intravenous doses of huA33-C825, the dextran-based clearing agent (CA), and the C825-haptens 177Lu-or 86Y-DOTA-Bn in mice bearing the SW1222 subcutaneous (s.c.) CRC xenograft model. Results Using optimized PRIT, therapeutic indices (TIs) for tumor radiation absorbed dose of 73 (tumor/blood) and 12 (tumor/kidney) were achieved. Estimated absorbed doses (cGy/MBq) to tumor, blood, liver, spleen, and kidney for single-cycle PRIT were 65.8, 0.9 (TI: 73), 6.3 (TI: 10), 6.6 (TI: 10), and 5.3 (TI: 12), respectively. Two cycles of PRIT treatment (66.6 or 111 MBq 177Lu-DOTA-Bn) were safe and effective, with 9/9 complete responses of established s.c. tumors (100–700 mm3) and 2/9 alive without recurrence >140 d. Tumor log kill in this model was estimated to be 2.1–3.0 based time to 500-mm3 tumor recurrence. In addition, PRIT dosimetry/diagnosis was performed by PET imaging of the positron-emitting DOTA-hapten 86Y-DOTA-Bn. Conclusions We have developed anti-GPA33 PRIT, as a triple-step theranostic strategy for pre-clinical detection, dosimetry and safe targeted radiotherapy of established human colorectal mouse xenografts. PMID:26596724

  9. 64Cu-ATSM Reflects pO2 Levels in Human Head and Neck Cancer Xenografts but Not in Colorectal Cancer Xenografts: Comparison with 64CuCl2

    DEFF Research Database (Denmark)

    Li, Fan; Jørgensen, Jesper T.; Forman, Julie

    2016-01-01

    colorectal tumors (HT29) after administration of either 64Cu-ATSM or 64CuCl2. Subsequently, tracks were generated and track markers were positioned in tumors to allow for registration of their exact location on the high-resolution CT scan. After completion of the CT scan, pO2 probe measurements were...... performed along each track. PET and CT images were coregistered and ROIs drawn on the basis of the location of track markers and pO2 probe measurement depth. A linear mixed model for repeated measures was applied for the comparison of PET tracer uptake to corresponding pO2 values. Results: Comparable uptake...

  10. Primary care practice organization influences colorectal cancer screening performance.

    Science.gov (United States)

    Yano, Elizabeth M; Soban, Lynn M; Parkerton, Patricia H; Etzioni, David A

    2007-06-01

    To identify primary care practice characteristics associated with colorectal cancer (CRC) screening performance, controlling for patient-level factors. Primary care director survey (1999-2000) of 155 VA primary care clinics linked with 38,818 eligible patients' sociodemographics, utilization, and CRC screening experience using centralized administrative and chart-review data (2001). Practices were characterized by degrees of centralization (e.g., authority over operations, staffing, outside-practice influence); resources (e.g., sufficiency of nonphysician staffing, space, clinical support arrangements); and complexity (e.g., facility size, academic status, managed care penetration), adjusting for patient-level covariates and contextual factors. Chart-based evidence of CRC screening through direct colonoscopy, sigmoidoscopy, or consecutive fecal occult blood tests, eliminating cases with documented histories of CRC, polyps, or inflammatory bowel disease. After adjusting for sociodemographic characteristics and health care utilization, patients were significantly more likely to be screened for CRC if their primary care practices had greater autonomy over the internal structure of care delivery (pmanagement and referral procedures are associated with significantly lower CRC screening performance. Competition with hospital resource demands may impinge on the degree of internal organization of their affiliated primary care practices.

  11. Factors influencing participation in colorectal cancer screening programs in Spain.

    Science.gov (United States)

    Vanaclocha-Espi, Mercedes; Ibáñez, Josefa; Molina-Barceló, Ana; Pérez, Elena; Nolasco, Andreu; Font, Rebeca; Pérez-Riquelme, Francisco; de la Vega, Mariola; Arana-Arri, Eunate; Oceja, MªElena; Espinàs, Josep Alfons; Portillo, Isabel; Salas, Dolores

    2017-12-01

    To analyze the sociodemographic and organizational factors influencing participation in population-based colorectal cancer screening programs (CRCSP) in Spain, a retrospective study was conducted in a cohort of people invited to participate in the first 3 screening rounds of 6 CRCSP from 2000 to 2012. Mixed logistic regression models were used to analyze the relationship between sociodemographic and organizational factors, such as the type of fecal occult blood test (FOBT) used and the FOBT delivery type. The analysis was performed separately in groups (Initial screening-first invitation, Subsequent invitation for previous never-responders, Subsequent invitation-regular, Subsequent invitation-irregular intervals). The results showed that, in the Initial screening-first invitation group, participation was higher in women than in men in all age groups (OR 1.05 in persons aged 50-59years and OR 1.12 in those aged 60-69years). Participation was also higher when no action was required to receive the FOBT kit, independently of the type of screening (Initial screening-first invitation [OR 2.24], Subsequent invitation for previous never-responders [OR 2.14], Subsequent invitation-regular [OR 2.03], Subsequent invitation-irregular intervals [OR 9.38]) and when quantitative rather than qualitative immunological FOBT (FIT) was offered (Initial screening-first invitation [OR 0.70], Subsequent invitation for previous never-responders [OR 0.12], Subsequent invitation-regular [OR 0.20]) or guaiac testing (Initial screening-first invitation [OR 0.81], Subsequent invitation for previous never-responders [OR 0.88], Subsequent invitation-regular [OR 0.73]). In conclusion, the results of this study show that screening participation could be enhanced by inclusion of the FOBT kit with the screening invitation and the use of the quantitative FIT. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. The use of matrigel has no influence on tumor development or PET imaging in FaDu human head and neck cancer xenografts

    DEFF Research Database (Denmark)

    Fliedner, Frederikke P.; Hansen, Anders Elias; Jorgensen, Jesper T.

    2016-01-01

    Background: In preclinical research MatrixgelTM Basement Membrane Matrix (MG) is used frequently for the establishment of syngeneic and xenograft cancer models. Limited information on its influence on parameters including; tumor growth, vascularization, hypoxia and imaging characteristics....... In sub study II ten mice from each group (+MG, n = 10; -MG, n = 10) were included and tumors collected for immunohistochemistry (IHC) analysis of tumor microenvironment including; proliferation ratio, micro vessel density, average vessel area, hypoxia, nuclear density, and necrosis. Tumors for IHC were...

  13. Colorectal cancer risk and patients' survival: influence of polymorphisms in genes somatically mutated in colorectal tumors

    Czech Academy of Sciences Publication Activity Database

    Huhn, S.; Bevier, M.; Pardini, Barbara; Naccarati, Alessio; Vodičková, Ludmila; Novotný, J.; Vodička, Pavel; Hemminki, K.; Försti, A.

    2014-01-01

    Roč. 25, č. 6 (2014), s. 759-769 ISSN 0957-5243 R&D Projects: GA ČR(CZ) GAP304/12/1585; GA ČR GAP304/10/1286 Grant - others:GA MŠk(CZ) Prvouk-P27/LF1/1 Institutional support: RVO:68378041 Keywords : colorectal cancer * risk * survival Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.735, year: 2014

  14. Correlations of 3T DCE-MRI Quantitative Parameters with Microvessel Density in a Human-Colorectal-Cancer Xenograft Mouse Model

    International Nuclear Information System (INIS)

    Ahn, Sung Jun; An, Chan Sik; Koom, Woong Sub; Song, Ho Taek; Suh, Jin Suck

    2011-01-01

    To investigate the correlation between quantitative dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) parameters and microvascular density (MVD) in a human-colon-cancer xenograft mouse model using 3 Tesla MRI. A human-colon-cancer xenograft model was produced by subcutaneously inoculating 1 X 106 DLD-1 human-colon-cancer cells into the right hind limbs of 10 mice. The tumors were allowed to grow for two weeks and then assessed using MRI. DCE-MRI was performed by tail vein injection of 0.3 mmol/kg of gadolinium. A region of interest (ROI) was drawn at the midpoints along the z-axes of the tumors, and a Tofts model analysis was performed. The quantitative parameters (Ktrans, Kep and Ve) from the whole transverse ROI and the hotspot ROI of the tumor were calculated. Immunohistochemical microvessel staining was performed and analyzed according to Weidner's criteria at the corresponding MRI sections. Additional Hematoxylin and Eosin staining was performed to evaluate tumor necrosis. The Mann-Whitney test and Spearman's rho correlation analysis were performed to prove the existence of a correlation between the quantitative parameters, necrosis, and MVD. Whole transverse ROI of the tumor showed no significant relationship between the MVD values and quantitative DCE-MRI parameters. In the hotspot ROI, there was a difference in MVD between low and high group of Ktrans and Kep that had marginally statistical significance (ps = 0.06 and 0.07, respectively). Also, Ktrans and Kep were found to have an inverse relationship with MVD (r -0.61, p = 0.06 in Ktrans; r = -0.60, p = 0.07 in Kep). Quantitative analysis of T1-weighted DCE-MRI using hotspot ROI may provide a better histologic match than whole transverse section ROI. Within the hotspots, Ktrans and Kep tend to have a reverse correlation with MVD in this colon cancer mouse model.

  15. Correlations of 3T DCE-MRI Quantitative Parameters with Microvessel Density in a Human-Colorectal-Cancer Xenograft Mouse Model

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Sung Jun; An, Chan Sik; Koom, Woong Sub; Song, Ho Taek; Suh, Jin Suck [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2011-11-15

    To investigate the correlation between quantitative dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) parameters and microvascular density (MVD) in a human-colon-cancer xenograft mouse model using 3 Tesla MRI. A human-colon-cancer xenograft model was produced by subcutaneously inoculating 1 X 106 DLD-1 human-colon-cancer cells into the right hind limbs of 10 mice. The tumors were allowed to grow for two weeks and then assessed using MRI. DCE-MRI was performed by tail vein injection of 0.3 mmol/kg of gadolinium. A region of interest (ROI) was drawn at the midpoints along the z-axes of the tumors, and a Tofts model analysis was performed. The quantitative parameters (Ktrans, Kep and Ve) from the whole transverse ROI and the hotspot ROI of the tumor were calculated. Immunohistochemical microvessel staining was performed and analyzed according to Weidner's criteria at the corresponding MRI sections. Additional Hematoxylin and Eosin staining was performed to evaluate tumor necrosis. The Mann-Whitney test and Spearman's rho correlation analysis were performed to prove the existence of a correlation between the quantitative parameters, necrosis, and MVD. Whole transverse ROI of the tumor showed no significant relationship between the MVD values and quantitative DCE-MRI parameters. In the hotspot ROI, there was a difference in MVD between low and high group of Ktrans and Kep that had marginally statistical significance (ps = 0.06 and 0.07, respectively). Also, Ktrans and Kep were found to have an inverse relationship with MVD (r -0.61, p = 0.06 in Ktrans; r = -0.60, p = 0.07 in Kep). Quantitative analysis of T1-weighted DCE-MRI using hotspot ROI may provide a better histologic match than whole transverse section ROI. Within the hotspots, Ktrans and Kep tend to have a reverse correlation with MVD in this colon cancer mouse model.

  16. Factors that influence treatment delay in patients with colorectal cancer

    Science.gov (United States)

    Zarcos-Pedrinaci, Irene; Fernández-López, Alberto; Téllez, Teresa; Rivas-Ruiz, Francisco; Rueda A, Antonio; Suarez-Varela, María Manuela Morales; Briones, Eduardo; Baré, Marisa; Escobar, Antonio; Sarasqueta, Cristina; de Larrea, Nerea Fernández; Aguirre, Urko; Quintana, José María; Redondo, Maximino

    2017-01-01

    A prospective study was performed of patients diagnosed with colorectal cancer (CRC), distinguishing between colonic and rectal location, to determine the factors that may provoke a delay in the first treatment (DFT) provided. 2749 patients diagnosed with CRC were studied. The study population was recruited between June 2010 and December 2012. DFT is defined as time elapsed between diagnosis and first treatment exceeding 30 days. Excessive treatment delay was recorded in 65.5% of the cases, and was more prevalent among rectal cancer patients. Independent predictor variables of DFT in colon cancer patients were a low level of education, small tumour, ex-smoker, asymptomatic at diagnosis and following the application of screening. Among rectal cancer patients, the corresponding factors were primary school education and being asymptomatic. We conclude that treatment delay in CRC patients is affected not only by clinicopathological factors, but also by sociocultural ones. Greater attention should be paid by the healthcare provider to social groups with less formal education, in order to optimise treatment attention. PMID:27888636

  17. The use of matrigel has no influence on tumor development or PET imaging in FaDu human head and neck cancer xenografts

    DEFF Research Database (Denmark)

    Fliedner, Frederikke P.; Hansen, Anders Elias; Jorgensen, Jesper T.

    2016-01-01

    is currently available. This study evaluates the potential effect of matrigel use in a human head and neck cancer xenograft model (FaDu; hypopharyngeal carcinoma) in NMRI nude mice. The FaDu cell line was chosen based on its frequent use in studies of cancer imaging and tumor microenvironment. Methods: NMRI...... nude mice (n = 34) were divided into two groups and subcutaneously injected with FaDu cells in medium either including (+MG) or excluding matrigel (-MG). In sub study I seven mice from each group (+MG, n = 7; -MG, n = 7) were 18F-fluorodeoxyglucose (18F-FDG) PET/CT scanned on Day 5, 8, 12, 15, and 19...... for the FaDu xenograft model evaluated. Tumors in the -MG group displayed increased angiogenesis compared to the +MG tumors. No difference in 18F-FDG PET uptake for tumors of different groups was found. Based on these observations the influence of matrigel on tumor imaging and tumor microenvironment seems...

  18. An examination of the psychosocial factors influencing colorectal cancer patients' communication of colorectal cancer patient risk with their siblings.

    Science.gov (United States)

    Lawsin, Catalina; Duhamel, Katherine; Itzkowitz, Steven; Brown, Karen; Lim, Helen; Jandorf, Lina

    2009-11-01

    This study examined psychosocial factors influencing colorectal cancer (CRC) patients' communication with their first-degree relatives regarding their CRC risk. Among a sample of CRC patients who were members of a colon registry in New York (n = 127), 60% reported discussing CRC risk with their siblings. These discussions were related to the CRC patients' age of diagnosis, such that those diagnosed before age 45 years were more likely to communicate with their siblings about CRC risk. Despite advances made in CRC prevention, compliance with screening recommendations among individuals who may be at familial risk for the disease is low. Perhaps this underrepresentation reflects how CRC patients communicate with their first-degree relatives about their potential risk for the disease. This study examined the psychosocial factors influencing whether CRC patients communicate with their siblings about CRC risk. The sample included CRC patients with siblings who enrolled in a colon disease registry at a NYC metropolitan hospital. Participants completed questionnaires regarding their current psychosocial functioning, perceived risk of sibling's development of CRC, and communication of CRC risk with their siblings. Patients were predominantly Caucasian, with a mean age of 60.4 years. Of the 127 patients, 60% engaged in discussions with their siblings regarding their CRC risk. Patients diagnosed with CRC before the age of 45 years were more likely to discuss the risk of CRC with their siblings (P siblings.

  19. Attenuated expression of HRH4 in colorectal carcinomas: a potential influence on tumor growth and progression

    International Nuclear Information System (INIS)

    Fang, Zhengyu; Wan, Jun; Yao, Wantong; Xiong, Yi; Li, Jiana; Liu, Li; Shi, Lei; Zhang, Wei; Zhang, Chao; Nie, Liping

    2011-01-01

    Earlier studies have reported the production of histamine in colorectal cancers (CRCs). The effect of histamine is largely determined locally by the histamine receptor expression pattern. Recent evidence suggests that the expression level of histamine receptor H4 (HRH4) is abnormal in colorectal cancer tissues. However, the role of HRH4 in CRC progression and its clinical relevance is not well understood. The aim of this study is to evaluate the clinical and molecular phenotypes of colorectal tumors with abnormal HRH4 expression. Immunoblotting, real-time PCR, immunofluorescence and immunohistochemistry assays were adopted to examine HRH4 expression in case-matched CRC samples (n = 107) and adjacent normal tissues (ANTs). To assess the functions of HRH4 in CRC cells, we established stable HRH4-transfected colorectal cells and examined cell proliferation, colony formation, cell cycle and apoptosis in these cells. The protein levels of HRH4 were reduced in most of the human CRC samples regardless of grade or Dukes classification. mRNA levels of HRH4 were also reduced in both early-stage and advanced CRC samples. In vitro studies showed that HRH4 over-expression caused growth arrest and induced expression of cell cycle proteins in CRC cells upon exposure to histamine through a cAMP -dependent pathway. Furthermore, HRH4 stimulation promoted the 5-Fu-induced cell apoptosis in HRH4-positive colorectal cells. The results from the current study supported previous findings of HRH4 abnormalities in CRCs. Expression levels of HRH4 could influence the histamine-mediated growth regulation in CRC cells. These findings suggested a potential role of abnormal HRH4 expression in the progression of CRCs and provided some new clues for the application of HRH4-specific agonist or antagonist in the molecular therapy of CRCs

  20. Attenuated expression of HRH4 in colorectal carcinomas: a potential influence on tumor growth and progression

    Directory of Open Access Journals (Sweden)

    Zhang Wei

    2011-05-01

    Full Text Available Abstract Background Earlier studies have reported the production of histamine in colorectal cancers (CRCs. The effect of histamine is largely determined locally by the histamine receptor expression pattern. Recent evidence suggests that the expression level of histamine receptor H4 (HRH4 is abnormal in colorectal cancer tissues. However, the role of HRH4 in CRC progression and its clinical relevance is not well understood. The aim of this study is to evaluate the clinical and molecular phenotypes of colorectal tumors with abnormal HRH4 expression. Methods Immunoblotting, real-time PCR, immunofluorescence and immunohistochemistry assays were adopted to examine HRH4 expression in case-matched CRC samples (n = 107 and adjacent normal tissues (ANTs. To assess the functions of HRH4 in CRC cells, we established stable HRH4-transfected colorectal cells and examined cell proliferation, colony formation, cell cycle and apoptosis in these cells. Results The protein levels of HRH4 were reduced in most of the human CRC samples regardless of grade or Dukes classification. mRNA levels of HRH4 were also reduced in both early-stage and advanced CRC samples. In vitro studies showed that HRH4 over-expression caused growth arrest and induced expression of cell cycle proteins in CRC cells upon exposure to histamine through a cAMP -dependent pathway. Furthermore, HRH4 stimulation promoted the 5-Fu-induced cell apoptosis in HRH4-positive colorectal cells. Conclusion The results from the current study supported previous findings of HRH4 abnormalities in CRCs. Expression levels of HRH4 could influence the histamine-mediated growth regulation in CRC cells. These findings suggested a potential role of abnormal HRH4 expression in the progression of CRCs and provided some new clues for the application of HRH4-specific agonist or antagonist in the molecular therapy of CRCs.

  1. The decreased influence of overall treatment time on the response of human breast tumor xenografts following prolongation of the potential doubling time (T{sub pot})

    Energy Technology Data Exchange (ETDEWEB)

    Sarkaria, Jann N; Fowler, John F; Lindstrom, Mary J; Jordan, V Craig; Mulcahy, R Timothy

    1995-02-15

    Purpose: Repopulation during fractionated radiotherapy has been postulated to result in a significant loss in local control in rapidly proliferating tumors. Clinical data suggest that accelerated fractionation schedules can overcome the influence of repopulation by limiting the overall treatment time. Unfortunately, accelerated therapy frequently leads to increased acute reactions, which may become dose limiting. An alternative to accelerated fractionation would be to decrease the rate of repopulation during therapy. To test the potential efficacy of this alternative, we examined the effect of reducing tumor proliferation rate on the response of MCF-7 human breast carcinoma xenografts treated with a short vs. a long course of fractionated therapy. To reduce the proliferation rate, we deprived nude mice transplanted with MCF-7 xenografts of the growth-stimulating hormone estradiol (E{sub 2}). We have previously reported that E{sub 2} deprivation increases the potential doubling time (T{sub pot}) for MCF-7 xenografts from a mean of 2.6 days to 5.3 days (p < 0.001). Methods and Materials: E{sub 2}-stimulated and E{sub 2}-deprived MCF-7 breast carcinoma xenografts were clamped hypoxically and irradiated with four fractions of 5 Gy each, using either a short (3-day) or long (9-day) treatment course. E{sub 2} stimulation was restored in all animals at the completion of irradiation. Radiation response was determined by regrowth time and regrowth delay of the irradiated tumors as compared to unirradiated controls. Results: Prolongation of therapy in rapidly proliferating, E{sub 2}-stimulated tumors (T{sub pot} {approx} 2.6 days) resulted in a significant decrease in regrowth time in two identical experiments. With results pooled for analysis, the regrowth times for the short and long treatments were 62 and 32 days, respectively (combined p < 0.001). The shorter regrowth times suggest that there was less overall tumor damage with the longer fractionated radiotherapy course

  2. The Influence of Tissue Ischemia on Biomarker Expression in Colorectal Cancer

    DEFF Research Database (Denmark)

    Havelund, Birgitte M; Aalund Olsen, Dorte; Andersen, Rikke F

    2013-01-01

    The aim of the present study was to investigate the influence of fixation delay and the perioperative ischemia on hypoxia inducible factor (HIF)-1α gene expression, HIF-1α protein expression, and immunohistochemical (IHC) expression of HIF-1α, GLUT-1, Bcl-2, and Ki-67 in colorectal cancer....... The study included 25 surgically removed colorectal tumors. Three sets of samples were collected readily after removal and exposed to 0, 30, and 60 minutes of delay of fixation or freezing. The perioperative ischemia time was registered. In each set of the samples, HIF-1α gene expression was analyzed...... by IHC. We found that the HIF-1α gene expression, HIF-1α protein concentration, and IHC expression of HIF-1α, GLUT-1, Ki-67, and Bcl-2 were not systematically affected by either the fixation or freezing delay of the tissue, the perioperative ischemia time, or the total ischemia time (perioperative...

  3. Influence of family history of colorectal cancer on health behavior and performance of early detection procedures: the SUN Project.

    Science.gov (United States)

    Martínez-Ochoa, Eva; Gómez-Acebo, Ines; Beunza, Juan-José; Rodríguez-Cundín, Paz; Dierssen-Sotos, Trinidad; Llorca, Javier

    2012-07-01

    The aim of this study is to explore the relationship between family history of colorectal cancer and both health behavior and screening procedures in a population cohort. This study is a cross-sectional analysis of 15,169 participants belonging to a prospective cohort study (the SUN Project) based on two self-reported questionnaires: one of them related to lifestyle and the other a semiquantitative food frequency questionnaire. We explored the influence of family history of colorectal cancer in lifestyles (consumption of alcohol, weight, and diet) and medical management behaviors (screening of chronic diseases). People with family history of colorectal cancer increased their number of colorectal cancer screening tests (adjusted odds ratio for fecal occult blood test: 1.98, 95% confidence interval: 1.48-2.65; and adjusted odds ratio for colonoscopy/sigmoidoscopy: 3.42, 2.69-4.36); nevertheless, health behavior changes in diet of relatives of colorectal cancer patients were undetectable. We show that individuals with a family history of colorectal cancer increase their compliance with screening tests, although they exhibit no better health-related behaviors than people without family history of colorectal cancer. Further prospective studies are required to confirm these results and to identify tools to empower the subjects to change their risk profile. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. The COLON study: Colorectal cancer: Longitudinal, Observational study on Nutritional and lifestyle factors that may influence colorectal tumour recurrence, survival and quality of life.

    Science.gov (United States)

    Winkels, Renate M; Heine-Bröring, Renate C; van Zutphen, Moniek; van Harten-Gerritsen, Suzanne; Kok, Dieuwertje E G; van Duijnhoven, Fränzel J B; Kampman, Ellen

    2014-05-27

    There is clear evidence that nutrition and lifestyle can modify colorectal cancer risk. However, it is not clear if those factors can affect colorectal cancer treatment, recurrence, survival and quality of life. This paper describes the background and design of the "COlorectal cancer: Longitudinal, Observational study on Nutritional and lifestyle factors that may influence colorectal tumour recurrence, survival and quality of life" - COLON - study. The main aim of this study is to assess associations of diet and other lifestyle factors, with colorectal cancer recurrence, survival and quality of life. We extensively investigate diet and lifestyle of colorectal cancer patients at diagnosis and during the following years; this design paper focusses on the initial exposures of interest: diet and dietary supplement use, body composition, nutrient status (e.g. vitamin D), and composition of the gut microbiota. The COLON study is a multi-centre prospective cohort study among at least 1,000 incident colorectal cancer patients recruited from 11 hospitals in the Netherlands. Patients with colorectal cancer are invited upon diagnosis. Upon recruitment, after 6 months, 2 years and 5 years, patients fill out food-frequency questionnaires; questionnaires about dietary supplement use, physical activity, weight, height, and quality of life; and donate blood samples. Diagnostic CT-scans are collected to assess cross-sectional areas of skeletal muscle, subcutaneous fat, visceral fat and intermuscular fat, and to assess muscle attenuation. Blood samples are biobanked to facilitate future analyse of biomarkers, nutrients, DNA etc. Analysis of serum 25-hydroxy vitamin D levels, and analysis of metabolomic profiles are scheduled. A subgroup of patients with colon cancer is asked to provide faecal samples before and at several time points after colon resection to study changes in gut microbiota during treatment. For all patients, information on vital status is retrieved by linkage with

  5. Factors Influencing Amount of Weekly Exercise Time in Colorectal Cancer Survivors.

    Science.gov (United States)

    Chou, Yun-Jen; Lai, Yeur-Hur; Lin, Been-Ren; Liang, Jin-Tung; Shun, Shiow-Ching

    Performing regular exercise of at least 150 minutes weekly has benefits for colorectal cancer survivors. However, barriers inhibit these survivors from performing regular exercise. The aim of this study was to explore exercise behaviors and significant factors influencing weekly exercise time of more than 150 minutes in colorectal cancer survivors. A cross-sectional study design was used to recruit participants in Taiwan. Guided by the ecological model of health behavior, exercise barriers were assessed including intrapersonal, interpersonal, and environment-related barriers. A multiple logistic regression was used to explore the factors associated with the amount of weekly exercise. Among 321 survivors, 57.0% of them had weekly exercise times of more than 150 minutes. The results identified multiple levels of significant factors related to weekly exercise times including intrapersonal factors (occupational status, functional status, pain, interest in exercise, and beliefs about the importance of exercise) and exercise barriers related to environmental factors (lack of time and bad weather). No interpersonal factors were found to be significant. Colorectal cancer survivors experienced low levels of physical and psychological distress. Multiple levels of significant factors related to exercise time including intrapersonal factors as well as exercise barriers related to environmental factors should be considered. Healthcare providers should discuss with their patients how to perform exercise programs; the discussion should address multiple levels of the ecological model such as any pain problems, functional status, employment status, and time limitations, as well as community environment.

  6. Radiosensitization by the histone deacetylase inhibitor vorinostat under hypoxia and with capecitabine in experimental colorectal carcinoma

    International Nuclear Information System (INIS)

    Saelen, Marie Grøn; Ree, Anne Hansen; Kristian, Alexandr; Fleten, Karianne Giller; Furre, Torbjørn; Hektoen, Helga Helseth; Flatmark, Kjersti

    2012-01-01

    The histone deacetylase inhibitor vorinostat is a candidate radiosensitizer in locally advanced rectal cancer (LARC). Radiosensitivity is critically influenced by hypoxia; hence, it is important to evaluate the efficacy of potential radiosensitizers under variable tissue oxygenation. Since fluoropyrimidine-based chemoradiotherapy (CRT) is the only clinically validated regimen in LARC, efficacy in combination with this established regimen should be assessed in preclinical models before a candidate drug enters clinical trials. Radiosensitization by vorinostat under hypoxia was studied in four colorectal carcinoma cell lines and in one colorectal carcinoma xenograft model by analysis of clonogenic survival and tumor growth delay, respectively. Radiosensitizing effects of vorinostat in combination with capecitabine were assessed by evaluation of tumor growth delay in two colorectal carcinoma xenografts models. Under hypoxia, radiosensitization by vorinostat was demonstrated in vitro in terms of decreased clonogenicity and in vivo as inhibition of tumor growth. Adding vorinostat to capecitabine-based CRT increased radiosensitivity of xenografts in terms of inhibited tumor growth. Vorinostat sensitized colorectal carcinoma cells to radiation under hypoxia in vitro and in vivo and improved therapeutic efficacy in combination with capecitabine-based CRT in vivo. The results encourage implementation of vorinostat into CRT in LARC trials

  7. Radiosensitization by the histone deacetylase inhibitor vorinostat under hypoxia and with capecitabine in experimental colorectal carcinoma.

    Science.gov (United States)

    Saelen, Marie Grøn; Ree, Anne Hansen; Kristian, Alexandr; Fleten, Karianne Giller; Furre, Torbjørn; Hektoen, Helga Helseth; Flatmark, Kjersti

    2012-09-27

    The histone deacetylase inhibitor vorinostat is a candidate radiosensitizer in locally advanced rectal cancer (LARC). Radiosensitivity is critically influenced by hypoxia; hence, it is important to evaluate the efficacy of potential radiosensitizers under variable tissue oxygenation. Since fluoropyrimidine-based chemoradiotherapy (CRT) is the only clinically validated regimen in LARC, efficacy in combination with this established regimen should be assessed in preclinical models before a candidate drug enters clinical trials. Radiosensitization by vorinostat under hypoxia was studied in four colorectal carcinoma cell lines and in one colorectal carcinoma xenograft model by analysis of clonogenic survival and tumor growth delay, respectively. Radiosensitizing effects of vorinostat in combination with capecitabine were assessed by evaluation of tumor growth delay in two colorectal carcinoma xenografts models. Under hypoxia, radiosensitization by vorinostat was demonstrated in vitro in terms of decreased clonogenicity and in vivo as inhibition of tumor growth. Adding vorinostat to capecitabine-based CRT increased radiosensitivity of xenografts in terms of inhibited tumor growth. Vorinostat sensitized colorectal carcinoma cells to radiation under hypoxia in vitro and in vivo and improved therapeutic efficacy in combination with capecitabine-based CRT in vivo. The results encourage implementation of vorinostat into CRT in LARC trials.

  8. Radiosensitization by the histone deacetylase inhibitor vorinostat under hypoxia and with capecitabine in experimental colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Saelen Marie

    2012-09-01

    Full Text Available Abstract Background The histone deacetylase inhibitor vorinostat is a candidate radiosensitizer in locally advanced rectal cancer (LARC. Radiosensitivity is critically influenced by hypoxia; hence, it is important to evaluate the efficacy of potential radiosensitizers under variable tissue oxygenation. Since fluoropyrimidine-based chemoradiotherapy (CRT is the only clinically validated regimen in LARC, efficacy in combination with this established regimen should be assessed in preclinical models before a candidate drug enters clinical trials. Methods Radiosensitization by vorinostat under hypoxia was studied in four colorectal carcinoma cell lines and in one colorectal carcinoma xenograft model by analysis of clonogenic survival and tumor growth delay, respectively. Radiosensitizing effects of vorinostat in combination with capecitabine were assessed by evaluation of tumor growth delay in two colorectal carcinoma xenografts models. Results Under hypoxia, radiosensitization by vorinostat was demonstrated in vitro in terms of decreased clonogenicity and in vivo as inhibition of tumor growth. Adding vorinostat to capecitabine-based CRT increased radiosensitivity of xenografts in terms of inhibited tumor growth. Conclusions Vorinostat sensitized colorectal carcinoma cells to radiation under hypoxia in vitro and in vivo and improved therapeutic efficacy in combination with capecitabine-based CRT in vivo. The results encourage implementation of vorinostat into CRT in LARC trials.

  9. Influence of preoperative life satisfaction on recovery and outcomes after colorectal cancer surgery - a prospective pilot study.

    Science.gov (United States)

    Romain, B; Rohmer, O; Schimchowitsch, S; Hübner, M; Delhorme, J B; Brigand, C; Rohr, S; Guenot, D

    2018-01-17

    Colorectal surgery has an important impact on a patient's quality of life, and postoperative rehabilitation shows large variations. To enhance the understanding of recovery after colorectal cancer, health-related quality of life has become a standard outcome measurement for clinical care and research. Therefore, we aimed to correlate the influence of preoperative global life satisfaction on subjective feelings of well-being with clinical outcomes after colorectal surgery. In this pilot study of consecutive colorectal surgery patients, various dimensions of feelings of preoperative life satisfaction were assessed using a self-rated scale, which was validated in French. Both objective (length of stay and complications) and subjective (pain, subjective well-being and quality of sleep) indicators of recovery were evaluated daily during each patient's hospital stay. A total of 112 patients were included. The results showed a negative relationship between life satisfaction and postoperative complications and a significant negative correlation with the length of stay. Moreover, a significant positive correlation between life satisfaction and the combined subjective indicators of recovery was observed. We have shown the importance of positive preoperative mental states and global life satisfaction as characteristics that are associated with an improved recovery after colorectal surgery. Therefore, patients with a good level of life satisfaction may be better able to face the consequences of colorectal surgery, which is a relevant parameter in supportive cancer care.

  10. The influence of the CHIEF pathway on colorectal cancer-specific mortality.

    Directory of Open Access Journals (Sweden)

    Martha L Slattery

    Full Text Available Many components of the CHIEF (Convergence of Hormones, Inflammation, and Energy Related Factors pathway could influence survival given their involvement in cell growth, apoptosis, angiogenesis, and tumor invasion stimulation. We used ARTP (Adaptive Rank Truncation Product to test if genes in the pathway were associated with colorectal cancer-specific mortality. Colon cancer (n = 1555 and rectal cancer (n = 754 cases were followed over five years. Age, center, stage at diagnosis, and tumor molecular phenotype were considered when calculating ARTP p values. A polygenic risk score was used to summarize the magnitude of risk associated with this pathway. The JAK/STAT/SOC was significant for colon cancer survival (PARTP = 0.035. Fifteen genes (DUSP2, INFGR1, IL6, IRF2, JAK2, MAP3K10, MMP1, NFkB1A, NOS2A, PIK3CA, SEPX1, SMAD3, TLR2, TYK2, and VDR were associated with colon cancer mortality (PARTP < 0.05; JAK2 (PARTP  = 0.0086, PIK3CA (PARTP = 0.0098, and SMAD3 (PARTP = 0.0059 had the strongest associations. Over 40 SNPs were significantly associated with survival within the 15 significant genes (PARTP < 0.05. SMAD3 had the strongest association with survival (HRGG 2.46 95% CI 1.44,4.21 PTtrnd = 0.0002. Seven genes (IL2RA, IL8RA, IL8RB, IRF2, RAF1, RUNX3, and SEPX1 were significantly associated with rectal cancer (PARTP < 0.05. The HR for colorectal cancer-specific mortality among colon cancer cases in the upper at-risk alleles group was 11.81 (95% CI 7.07, 19. 74 and was 10.99 (95% CI 5.30, 22.78 for rectal cancer. These results suggest that several genes in the CHIEF pathway are important for colorectal cancer survival; the risk associated with the pathway merits validation in other studies.

  11. [Gender-specific influences on incidence, screening, treatment, and outcome of colorectal cancer].

    Science.gov (United States)

    Grundmann, R T; Meyer, F

    2013-08-01

    This overview comments on potential gender-specific differences in incidence, anatomic site, screening, treatment, and outcome in patients with colorectal cancer (CRC). For the literature review, the Medline database (PubMed) was searched under the key words "colorectal carcinoma AND gender" and "gender differences AND colorectal cancer". Publications of the last 9 years (2005-2013) were firstly retrieved. CRC is more commonly observed in men than in women, with the higher tumour risk for men being limited to the distal colon and rectum. Risk factors for the development of CRC include overweight and obesity, this relationship is more pronounced for men than for women. The extent to which gender is a prognostic factor for patient survival is controversial. A better survival of women compared to men is found especially in the younger age groups, from which can be derived a protective effect of oestrogens on the development of CRC. As for the frequency with which men and women undergo a screening of CRC, sometimes higher screening rates have been reported for men than women, however, the socio-economic status of persons invited to participate has much more influence on screening attendance than gender. An analysis of surgical procedures indicates that it is more difficult to perform the low anterior resection of the rectum in men than women, with the result that men managed by less experienced surgeons are more likely to receive abdominoperineal excision. Furthermore, the risk of anastomotic leakage is higher in men than women. The essential gender difference, however, is the longer life expectancy of women compared to men which has been not always clearly (risk adjusted) elaborated in the studies available so far. This difference alone can already explain at a high rate the poorer prognosis of right-sided colon cancers compared to left-sided cancers. Comparable levels of CRC risk are reached in women as compared to men at a higher age. This may influence the

  12. Polymorphisms in xenobiotic metabolizing enzymes and diet influence colorectal adenoma risk.

    Science.gov (United States)

    Northwood, Emma L; Elliott, Faye; Forman, David; Barrett, Jennifer H; Wilkie, Murray J V; Carey, Francis A; Steele, Robert J C; Wolf, Roland; Bishop, Timothy; Smith, Gillian

    2010-05-01

    We have earlier shown that diet and xenobiotic metabolizing enzyme genotypes influence colorectal cancer risk, and now investigate whether similar associations are seen in patients with premalignant colorectal adenomas (CRA), recruited during the pilot phase of the Scottish Bowel Screening Programme. Nineteen polymorphisms in 13 genes [cytochrome P450 (P450), glutathione S-transferase (GST), N-acetyl transferase, quinone reductase (NQ01) and microsomal epoxide hydrolase (EPHX1) genes] were genotyped using multiplex PCR or Taqman-based allelic discrimination assays and analyzed in conjunction with diet, assessed by food frequency questionnaire, in a case-control study [317 CRA cases (308 cases genotyped), 296 controls]. Findings significant at a nominal 5% level are reported. CRA risk was inversely associated with fruit (P=0.02, test for trend) and vegetable (P=0.001, test for trend) consumption. P450 CYP2C9*3 heterozygotes had reduced CRA risk compared with homozygotes for the reference allele [odds ratio (OR): 0.60; 95% confidence interval (CI): 0.36-0.99], whereas CYP2D6*4 homozygotes (OR: 2.72; 95% CI: 1.18-6.27) and GSTM1 'null' individuals (OR: 1.43; 95% CI: 1.04-1.98) were at increased risk. The protective effect of fruit consumption was confined to GSTP1 (Ala114Val) reference allele homozygotes (OR: 0.49; 95% CI: 0.34-0.71, P=0.03 for interaction). CRA risk was not associated with meat consumption, although a significant interaction between red meat consumption and EPHX1 (His139Arg) genotype was noted (P=0.02 for interaction). We report the novel associations between P450 genotype and CRA risk, and highlight the risk association with GSTM1 genotype, common to our CRA and cancer case-control series. In addition, we report a novel modifying influence of GSTP1 genotype on dietary chemoprevention. These novel findings require independent confirmation.

  13. Segmental distribution of some common molecular markers for colorectal cancer (CRC): influencing factors and potential implications.

    Science.gov (United States)

    Papagiorgis, Petros Christakis

    2016-05-01

    Proximal and distal colorectal cancers (CRCs) are regarded as distinct disease entities, evolving through different genetic pathways and showing multiple clinicopathological and molecular differences. Segmental distribution of some common markers (e.g., KRAS, EGFR, Ki-67, Bcl-2, COX-2) is clinically important, potentially affecting their prognostic or predictive value. However, this distribution is influenced by a variety of factors such as the anatomical overlap of tumorigenic molecular events, associations of some markers with other clinicopathological features (stage and/or grade), and wide methodological variability in markers' assessment. All these factors represent principal influences followed by intratumoral heterogeneity and geographic variation in the frequency of detection of particular markers, whereas the role of other potential influences (e.g., pre-adjuvant treatment, interaction between markers) remains rather unclear. Better understanding and elucidation of the various influences may provide a more accurate picture of the segmental distribution of molecular markers in CRC, potentially allowing the application of a novel patient stratification for treatment, based on particular molecular profiles in combination with tumor location.

  14. The COLON study: Colorectal cancer: Longitudinal, Observational study on Nutritional and lifestyle factors that may influence colorectal tumour recurrence, survival and quality of life

    NARCIS (Netherlands)

    Winkels, R.M.; Heine-Bröring, R.C.; Zutphen, van M.; Harten-Gerritsen, van A.S.; Kok, D.E.G.; Duijnhoven, van F.J.B.; Kampman, E.

    2014-01-01

    Background There is clear evidence that nutrition and lifestyle can modify colorectal cancer risk. However, it is not clear if those factors can affect colorectal cancer treatment, recurrence, survival and quality of life. This paper describes the background and design of the “COlorectal cancer:

  15. The COLON study: Colorectal cancer: Longitudinal, Observational study on Nutritional and lifestyle factors that may influence colorectal tumour recurrence, survival and quality of life

    NARCIS (Netherlands)

    Winkels, R.M.; Heine-Broring, R.C.; Zutphen, M. van; Harten-Gerritsen, S. van; Kok, D.E.; Duijnhoven, F.J.B. van; Kampman, E.

    2014-01-01

    BACKGROUND: There is clear evidence that nutrition and lifestyle can modify colorectal cancer risk. However, it is not clear if those factors can affect colorectal cancer treatment, recurrence, survival and quality of life. This paper describes the background and design of the "COlorectal cancer:

  16. Adjuvant chemotherapy for colorectal cancer: age differences in factors influencing patients' treatment decisions

    Directory of Open Access Journals (Sweden)

    Jorgensen ML

    2013-08-01

    Full Text Available Mikaela L Jorgensen,1,2 Jane M Young,1,2 Michael J Solomon1,31Surgical Outcomes Research Centre (SOuRCe, Sydney School of Public Health, University of Sydney and Sydney Local Health District, NSW, Australia; 2Cancer Epidemiology and Services Research (CESR, Sydney School of Public Health, University of Sydney, NSW, Australia; 3Discipline of Surgery, University of Sydney, NSW, AustraliaPurpose: Older colorectal cancer patients are significantly less likely than younger patients to receive guideline-recommended adjuvant chemotherapy. Previous research has indicated that patient refusal of treatment is a contributing factor. This study aimed to identify potential barriers to adjuvant chemotherapy use in older patients by examining the associations between patient age, factors influencing chemotherapy treatment decisions, and preferences for information and decision-making involvement.Patients and methods: Sixty-eight patients who underwent surgery for colorectal cancer in Sydney, Australia, within the previous 24 months completed a self-administered survey.Results: Fear of dying, health status, age, quality of life, and understanding treatment procedures and effects were significantly more important to older patients (aged ≥65 years than younger patients in deciding whether to accept chemotherapy (all P < 0.05. Reducing the risk of cancer returning and physician trust were important factors for all patients. Practical barriers such as traveling for treatment and cost were rated lowest. Older patients preferred less information and involvement in treatment decision making than younger patients. However, 60% of the older group wanted detailed information about chemotherapy, and 83% wanted some involvement in decision making. Those preferring less information and involvement still rated many factors as important in their decision making, including understanding treatment procedures and effects.Conclusion: A range of factors appears to influence

  17. Travel distance influences readmissions in colorectal cancer patients-what the primary operative team needs to know.

    Science.gov (United States)

    Kelley, Katherine A; Young, J Isaac; Bassale, Solange; Herzig, Daniel O; Martindale, Robert G; Sheppard, Brett C; Lu, Kim C; Tsikitis, V Liana

    2018-07-01

    Many colorectal cancer patients receive complex surgical care remotely. We hypothesized that their readmission rates would be adversely affected after accounting for differences in travel distance from primary/index hospital and correlate with mortality. We identified 48,481 colorectal cancer patients in the Surveillance, Epidemiology and End Results (SEER)-Medicare database. Travel distance was calculated, using Google Maps, and SAS. Multivariate negative binomial regression was used to identify factors associated with readmission rates. Overall survival was analyzed, using Kaplan-Meier and Cox proportional hazard. Thirty-day readmissions occurred in 14.9% of the cohort, 27.5% of which were to a nonindex hospital. In the colon and rectal cancer cohorts, readmissions were 14.5% and 16.5%, respectively. Rectal cancer patients had an increase in readmission by 13% (incidence rate ratios [IRR] 1.13; 95% confidence interval [CI] 1.05-1.21). Factors associated with readmission were male gender, advanced disease, length of stay (LOS), discharge disposition, hospital volume, Charlson score, and poverty level (P < 0.05). Greater distance traveled increased the likelihood of readmission but did not affect mortality. Travel distance influences readmission rates but not mortality. Discharge readiness to decrease readmissions is essential for colorectal cancer patients discharged from index hospitals. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Factors influencing choice of chemotherapy in metastatic colorectal cancer (mCRC

    Directory of Open Access Journals (Sweden)

    Rossi L

    2013-11-01

    Full Text Available Luigi Rossi, Foteini Vakiarou, Federica Zoratto, Loredana Bianchi, Anselmo Papa, Enrico Basso, Monica Verrico, Giuseppe Lo Russo, Salvatore Evangelista, Guilia Rinaldi, Francesca Perrone-Congedi, Gian Paolo Spinelli, Valeria Stati, Davide Caruso, Alessandra Prete, Silverio TomaoDepartment of Medico-Surgical Sciences and Biotechnologies, "Sapienza" University of Rome, Rome, Italy; Oncology Unit, ICOT, Latina, ItalyAbstract: Management of metastatic colorectal cancer requires a multimodal approach and must be performed by an experienced, multidisciplinary expert team. The optimal choice of the individual treatment modality, according to disease localization and extent, tumor biology, and patient clinical characteristics, will be one that can maintain quality of life and long-term survival, and even cure selected patients. This review is an overview of the different therapeutic approaches available in metastatic colorectal cancer, for the purpose of defining personalized therapeutic algorithms according to tumor biology and patient clinical features.Keywords: metastatic colorectal cancer, patient clinical features, tumor biology, multidisciplinary approach

  19. Factors influencing choice of chemotherapy in metastatic colorectal cancer (mCRC)

    International Nuclear Information System (INIS)

    Rossi, Luigi; Vakiarou, Foteini; Zoratto, Federica; Bianchi, Loredana; Papa, Anselmo; Basso, Enrico; Verrico, Monica; Lo Russo, Giuseppe; Evangelista, Salvatore; Rinaldi, Guilia; Perrone-Congedi, Francesca; Spinelli, Gian Paolo; Stati, Valeria; Caruso, Davide; Prete, Alessandra; Tomao, Silverio

    2013-01-01

    Management of metastatic colorectal cancer requires a multimodal approach and must be performed by an experienced, multidisciplinary expert team. The optimal choice of the individual treatment modality, according to disease localization and extent, tumor biology, and patient clinical characteristics, will be one that can maintain quality of life and long-term survival, and even cure selected patients. This review is an overview of the different therapeutic approaches available in metastatic colorectal cancer, for the purpose of defining personalized therapeutic algorithms according to tumor biology and patient clinical features

  20. Multiple factors influence compliance with colorectal cancer staging recommendations: an exploratory study

    Directory of Open Access Journals (Sweden)

    Khalifa Mahmoud A

    2008-02-01

    Full Text Available Abstract Background For patients with colorectal cancer (CRC retrieval by surgeons, and assessment by pathologists of at least 12 lymph nodes (LNs predicts the need for adjuvant treatment and improved survival. Different interventions (educational presentation, engaging clinical opinion leaders, performance data sent to hospital executives to improve compliance with this practice had variable results. This exploratory study examined factors hypothesized to have influenced the outcome of those interventions. Methods Semi-structured interviews were conducted with 26 surgeons and pathologists at eleven hospitals. Clinicians were identified by intervention organizers, public licensing body database, and referral from interviewees. An interview guide incorporating open-ended questions was pilot-tested on one surgeon and pathologist. A single investigator conducted all interviews by phone. Transcripts were analyzed independently by two investigators using a grounded approach,ho then compared findings to resolve differences. Results Improvements in LN staging practice may have occurred largely due to educational presentations that created awareness, and self-initiated changes undertaken by pathologists. Executives that received performance data may not have shared this with staff, and opinion leaders engaged to promote compliance may not have fulfilled their roles. Barriers to change that are potentially amenable to quality improvement included perceptions about the practice (perceived lack of evidence for the need to examine at least 12 LNs and associated responsibilities (blaming other profession, technical issues (need for pathology assistants, better clearing solutions and laboratory facilities, and a lack of organizational support for multidisciplinary interaction (little communication between surgeons and pathologists or quality improvement (no change leaders or capacity for monitoring. Conclusion Use of an exploratory approach provided an in

  1. Influence of body composition profile on outcomes following colorectal cancer surgery.

    Science.gov (United States)

    Malietzis, G; Currie, A C; Athanasiou, T; Johns, N; Anyamene, N; Glynne-Jones, R; Kennedy, R H; Fearon, K C H; Jenkins, J T

    2016-04-01

    Muscle depletion is characterized by reduced muscle mass (myopenia), and increased infiltration by intermuscular and intramuscular fat (myosteatosis). This study examined the role of particular body composition profiles as prognostic markers for patients with colorectal cancer undergoing curative resection. Patients with colorectal cancer undergoing elective surgical resection between 2006 and 2011 were included. Lumbar skeletal muscle index (LSMI), visceral adipose tissue (VAT) surface area and mean muscle attenuation (MA) were calculated by analysis of CT images. Reduced LSMI (myopenia), increased VAT (visceral obesity) and low MA (myosteatosis) were identified using predefined sex-specific skeletal muscle index values. Univariable and multivariable Cox regression models were used to determine the role of different body composition profiles on outcomes. Some 805 patients were identified, with a median follow-up of 47 (i.q.r. 24·9-65·6) months. Multivariable analysis identified myopenia as an independent prognostic factor for disease-free survival (hazard ratio (HR) 1·53, 95 per cent c.i. 1·06 to 2·39; P = 0·041) and overall survival (HR 1·70, 1·25 to 2·31; P cancer survival for patients with colorectal cancer. Muscle depletion may represent a modifiable risk factor in patients with colorectal cancer and needs to be targeted as a relevant endpoint of health recommendations. © 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.

  2. Functional screening identifies miRNAs influencing apoptosis and proliferation in colorectal cancer

    DEFF Research Database (Denmark)

    Christensen, Lise Lotte; Holm, Anja; Rantala, Juha

    2014-01-01

    MicroRNAs (miRNAs) play a critical role in many biological processes and are aberrantly expressed in human cancers. Particular miRNAs function either as tumor suppressors or oncogenes and appear to have diagnostic and prognostic significance. Although numerous miRNAs are dys-regulated in colorect...

  3. Does geography influence the treatment and outcomes of colorectal cancer? A population-based analysis.

    Science.gov (United States)

    Helewa, Ramzi M; Turner, Donna; Wirtzfeld, Debrah; Park, Jason; Hochman, David; Czaykowski, Piotr; Singh, Harminder; Shu, Emma; Xue, Lin; McKay, Andrew

    2013-06-17

    The Canadian province of Manitoba covers a large geographical area but only has one major urban center, Winnipeg. We sought to determine if regional differences existed in the quality of colorectal cancer care in a publicly funded health care system. This was a population-based historical cohort analysis of the treatment and outcomes of Manitobans diagnosed with colorectal cancer between 2004 and 2006. Administrative databases were utilized to assess quality of care using published quality indicators. A total of 2,086 patients were diagnosed with stage I to IV colorectal cancer and 42.2% lived outside of Winnipeg. Patients from North Manitoba had a lower odds of undergoing major surgery after controlling for other confounders (odds ratio (OR): 0.48, 95% confidence interval (CI): 0.26 to 0.90). No geographic differences existed in the quality measures of 30-day operative mortality, consultations with oncologists, surveillance colonoscopy, and 5-year survival. However, there was a trend towards lower survival in North Manitoba. We found minimal differences by geography. However, overall compliance with quality measures is low and there are concerning trends in North Manitoba. This study is one of the few to evaluate population-based benchmarks for colorectal cancer therapy in Canada.

  4. Influence of type 2 diabetes mellitus on Khorana venous thromboembolism risk in colorectal cancer patients

    Directory of Open Access Journals (Sweden)

    Ruyao Wang

    Full Text Available Background: Many studies have documented the association between venous thromboembolism (VTE and colorectal cancer (CRC. The Khorana model is a VTE risk assessment model for predicting cancer-associated thrombosis. Type 2 diabetes (T2DM has also been reported to increase the risk of VTE. Purpose: The aim of this study was to investigate the influence of T2DM on Khorana VTE risk in CRC patients and to explore the relationship between Khorana VTE category and CRC clinicopathological factors. Methods: This analysis included 615 CRC patients (205 with T2DM. Fibrinogen and D-dimer levels were compared within each group. A comparison was made of the proportion of patients in different Khorana VTE risk categories in CRC patients with and without T2DM. The association between Khorana VTE risk category and clinicopathological factors among all the CRC patients was evaluated. Results: Fibrinogen levels of CRC patients with T2DM were significantly higher than those of non-diabetes patients (4.13 ± 1.06 vs 3.94 ± 0.98, p < 0.001. A higher proportion of CRC patients with T2DM were in the Khorana intermediate-to-high risk category (H = 4.749, p = 0.029. Female sex, diabetes, colon location (compared with rectum, larger tumor size, advanced pT stage and pN stage were correlated with the intermediate-to-high Khorana VTE risk category, with odd ratios (95% confidence intervals [CI] of 1.537 (1.064-2.220, 1.499 (1.027-2.186, 2.313 (1.588-3.370, 2.284 (1.542-3.383, 4.429 (2.088-9.396 and 1.822 (1.230-2.698, respectively. Conclusion: T2DM increases Khorana VTE risk in CRC patients. Female sex, diabetes, colon location, large tumor size and poor stage are associated with the intermediate-to-high Khorana VTE risk category.

  5. Colorectal polyps

    Science.gov (United States)

    Intestinal polyps; Polyps - colorectal; Adenomatous polyps; Hyperplastic polyps; Villous adenomas; Serrated polyp; Serrated adenoma; Precancerous polyps; Colon cancer - polyps; Bleeding - colorectal polyps

  6. Influence of inhibitors of serotonin uptake on intestinal epithelium and colorectal carcinomas.

    Science.gov (United States)

    Tutton, P J; Barkla, D H

    1982-08-01

    Previous studies have shown that in certain tissues, including colonic carcinomas, cell proliferation may be promoted by serotonin, and indirect evidence suggests that the effects of this amine on colonic tumours involves a cellular-uptake mechanism. In the present study, two specific inhibitors of serotonin uptake, Citalopram and Fluoxetine, are examined for their effects on cell proliferation and tumour growth. Each of the agents was found to suppress cell division in dimethylhydrazine-induced colonic tumours in rats, and to retard the growth of 2 out of 3 lines of human colonic tumours propagated as xenografts in immune-deprived mice.

  7. Ureteral catheters for colorectal surgery: Influence on operative times and complication outcomes: An observational study

    Directory of Open Access Journals (Sweden)

    Julio T. Chong

    2018-03-01

    Full Text Available Purpose: Placement of pre-operative ureteral catheters for colorectal surgery can aid in the identification of ureteral injuries. This study investigates whether simultaneous ureteral catheterization with surgery skin preparation can minimize operating room times without increasing post-operative complications. Materials and Methods: Patients undergoing simultaneous colorectal surgery skin preparation and placement of pre-operative ureteral catheters (n=21 were compared to those who underwent these events sequentially (n=28. Operative time-points of anesthesia ready (AR, surgery procedure start (PS, dorsal lithotomy and catheter insertion (CI times were compared to assess for differences between groups. Complications were compared between groups. Results: There were no differences in age, gender, body mass index (BMI, American Society of Anesthesiologists (ASA, comorbidities, current procedure terminology (CPT or International Classification of Diseases, 9th revision (ICD-9 codes between groups. Simultaneous catheterization saved 11.82 minutes of operative time between CI to PS (p=0.005, t-test. There was a significant difference in mean time between CI to PS (11.82 minutes, p=0.008 between simultaneous and sequential ureteral catheterization groups in a linear regression multivariate analysis controlling for age, BMI, CPT and ICD-9 codes. There were 4 complications in the simultaneous (19% and 3 in the sequential group (11% (p=0.68. Conclusions: Ureteral catheterization and colorectal surgery skin preparation in a simultaneous fashion decreases the time between CI and PS without significant increase in complications. Mean time saved with simultaneous ureteral catheterization was 11.82 minutes per case. Simultaneous ureteral catheterization may be an option in colorectal surgery and may result in cost savings without additional complications.

  8. The Influence of Tissue Ischemia Time on RNA Integrity and Patient-Derived Xenografts (PDX) Engraftment Rate in a Non-Small Cell Lung Cancer (NSCLC) Biobank.

    Science.gov (United States)

    Guerrera, Francesco; Tabbò, Fabrizio; Bessone, Luca; Maletta, Francesca; Gaudiano, Marcello; Ercole, Elisabetta; Annaratone, Laura; Todaro, Maria; Boita, Monica; Filosso, Pier Luigi; Solidoro, Paolo; Delsedime, Luisa; Oliaro, Alberto; Sapino, Anna; Ruffini, Enrico; Inghirami, Giorgio

    2016-01-01

    Bio-repositories are invaluable resources to implement translational cancer research and clinical programs. They represent one of the most powerful tools for biomolecular studies of clinically annotated cohorts, but high quality samples are required to generate reliable molecular readouts and functional studies. The objective of our study was to define the impact of cancer tissue ischemia time on RNA and DNA quality, and for the generation of Patient-Derived Xenografts (PDXs). One-hundred thirty-five lung cancer specimens were selected among our Institutional BioBank samples. Associations between different warm (surgical) and cold (ex-vivo) ischemia time ranges and RNA quality or PDXs engraftment rates were assessed. RNA quality was determined by RNA integrity number (RINs) values. Fresh viable tissue fragments were implanted subcutaneously in NSG mice and serially transplanted. RNAs with a RIN>7 were detected in 51% of the sample (70/135), with values of RIN significantly lower (OR 0.08, P = 0.01) in samples preserved for more than 3 hours before cryopreservation. Higher quality DNA samples had a concomitant high RIN. Sixty-three primary tumors (41 adenocarcinoma) were implanted with an overall engraftment rate of 33%. Both prolonged warm (>2 hours) and ex-vivo ischemia time (>10 hours) were associated to a lower engraftment rate (OR 0.09 P = 0.01 and OR 0.04 P = 0.008, respectively). RNA quality and PDXs engraftment rate were adversely affected by prolonged ischemia times. Proper tissue collection and processing reduce failure rate. Overall, NSCLC BioBanking represents an innovative modality, which can be successfully executed in routine clinical settings, when stringent Standard Operating Procedures are adopted.

  9. Mucinous Colorectal Adenocarcinoma: Influence of EGFR and E-Cadherin Expression on Clinicopathologic Features and Prognosis.

    Science.gov (United States)

    Foda, Abd AlRahman M; AbdelAziz, Azza; El-Hawary, Amira K; Hosni, Ali; Zalata, Khalid R; Gado, Asmaa I

    2015-08-01

    Previous studies have shown conflicting results on epidermal growth factor receptor (EGFR) and E-cadherin expression in colorectal carcinoma and their prognostic significance. To the best of our knowledge, this study is the first to investigate EGFR and E-cadherin expression, interrelation and relation to clinicopathologic, histologic parameters, and survival in rare colorectal mucinous adenocarcinoma (MA). In this study, we studied tumor tissue specimens from 150 patients with colorectal MA and nonmucinous adenocarcinoma (NMA). High-density manual tissue microarrays were constructed using modified mechanical pencil tips technique, and immunohistochemistry for EGFR and E-cadherin was performed. All relations were analyzed using established statistical methodologies. NMA expressed EGFR and E-cadherin in significantly higher rates with significant heterogenous pattern than MA. EGFR and E-cadherin positivity rates were significantly interrelated in both NMA and MA groups. In the NMA group, high EGFR expression was associated with old age, male sex, multiplicity of tumors, lack of mucinous component, and association with schistosomiasis. However, in the MA group, high EGFR expression was associated only with old age and MA subtype rather than signet ring carcinoma subtype. Conversely, high E-cadherin expression in MA cases was associated with old age, fungating tumor configuration, MA subtype, and negative intratumoral lymphocytic response. However, in the NMA cases, none of these factors was statistically significant. In a univariate analysis, neither EGFR nor E-cadherin expression showed a significant impact on disease-free or overall survival. Targeted therapy against EGFR and E-cadherin may not be useful in patients with MA. Neither EGFR nor E-cadherin is an independent prognostic factor in NMA or MA.

  10. Influence of DC-CIK in advanced colorectal cancer patients on T lymphocyte subsets and cytokines

    Directory of Open Access Journals (Sweden)

    Rong Wang

    2016-07-01

    Full Text Available Objective: To explore the effects of dendritic cells (DC-cytokine induced killer cells (CIK treatment on T lymphocyte subsets and cytokines in patients with advanced colorectal cancer. Methods: A total of 84 cases patients with advanced colorectal cancer were divided into two groups according to random number table method, each 42 cases, both two groups were given FOLFOX scheme chemotherapy, on the basis, the observation group were given supplementary DC-CIK treatment, compared the T lymphocy te subgroup: CD3+, CD4+, CD8+, CD4+/CD8+, Th1 cytokines, interleukin-2 (IL-2 and interferon gamma-γ (FN-γ, Th2 cytokines: interleukin 6 (IL-6, interleukin 4 (IL-4 of the two groups before and after treatment. Results: Compared with before treatment, the CD3+, CD4+, CD8+, CD4+/CD8+, Th1 cytokines IL-2 and IFN-γ in observation group were significantly higher than after treatment , the CD3+, CD4+, CD8+, CD4+/CD8+, Th1 cytokines IL-2 and IFN-γ in control group were significantly lower than after treatment, and the differences were all statistically significant; The CD3+, CD4+, CD8+, CD4+/CD8+, Th1 cytokines IL-2 and IFN-γ in observation group after treatment were significantly higher than those in control group after treatment with statistical difference; CD8+, Th2 cytokines IL-4, IL-6 in two groups had no statistical significance before and after treatment. Conclusion: Chemotherapy can cause the immune function restrained in patients with advanced colorectal cancer, and DC-CIK supplementary therapy can significantly improve the immune function, enhance the anti tumor immune responses.

  11. The influence of contextual factors on patient involvement during follow-up consultations after colorectal cancer surgery

    DEFF Research Database (Denmark)

    Thomsen, Thora G; Soelver, Lisbeth; Hølge-Hazelton, Bibi

    2017-01-01

    AIMS AND OBJECTIVES: To identify the contextual factors that influence individual patient involvement during colorectal cancer surgical follow-up consultations. BACKGROUND: The healthcare system is subject to the requirement and expectation of greater involvement of patients and relatives...... the identification of current contextual factors. RESULTS: The results showed five contextual factors that seemed to have an impact on patient involvement. The first, 'Two dimensions of patient involvement: treatment-oriented and person-oriented' highlighted a dual interpretation of patient involvement....... Increased patient involvement requires the development and implementation of new communication initiatives. Research shows that it is also necessary to consider the contextual circumstances surrounding patient involvement in specific situations. DESIGN: Case study of a single Danish outpatient clinic, which...

  12. Existing evidence on the influence of prebiotic intake on the risk of colorectal cancer

    Directory of Open Access Journals (Sweden)

    Mireia Hidalgo-Garcia

    2013-03-01

    Full Text Available Colorectal cancer is one of the most common cancers worldwide. Among the risk of developing colorectal cancer and the intestinal microbiota there is a complex relationship that can be modified by diet. The effect of prebiotics on the composition and colonic microbiota activity can produce beneficial changes in the altered flora of pacients with colon cancer. Of all the prebiotic inulin HP and sinergil (30% oligofructose and 70% inulin are supposed to be the ones that keep a closer relationship with the tumor. This phenomenon could be explained by the long chain fructans. The animal studies observed that administration of prebiotics reduces the number and multiplicity of aberrant crypt foci, reduce the number and lifetime of the tumors, inhibits their growth and potentiates the effect of different chemotherapeutic drugs. The results obtained in rodents that are intended to simulate genetic predisposition are not homogeneous. Some human studies, mostly healthy, observed changes in the composition of the microbiota, in the bile acid profile and the short chain fatty acids, but the results differ among studies and no conclusive results are obtained.

  13. The influence of marital status on stage at diagnosis and survival of patients with colorectal cancer.

    Science.gov (United States)

    Li, Qingguo; Gan, Lu; Liang, Lei; Li, Xinxiang; Cai, Sanjun

    2015-03-30

    Marital status was found to be an independent prognostic factor for survival in various cancer types, but it hasn't been fully studied in colorectal cancer (CRC). The Surveillance, Epidemiology and End Results database was used to compare survival outcomes with marital status in each stage. In total, 112, 776 eligible patients were identified. Patients in the widowed group were more frequently elderly women, more common of colon cancer, and more stage I/II in tumor stage (P married group (94.72% VS 94.10%). Married CRC patients had better 5year cause-specific survival (CSS) than those unmarried (P married patients at stage I (94.8% vs 89.8%, P vs 76.5%, P vs 53.9%, P VS 8.2%, P unmarried patients were at greater risk of cancer specific mortality. Despite favorable clinicpathological characteristics, widowed patients were at highest risk of death compared with other groups.

  14. A qualitative study exploring health perceptions and factors influencing participation in health behaviors in colorectal cancer survivors.

    Science.gov (United States)

    Hardcastle, Sarah J; Maxwell-Smith, Chloe; Zeps, Nik; Platell, Cameron; O'Connor, Moira; Hagger, Martin S

    2017-02-01

    The purpose of the study was to explore colorectal cancer survivors' health perceptions following cessation of active treatment for cancer and to explore the factors influencing participation in health-promoting behaviors that may help reduce cardiovascular disease risk. Face-to-face interviews were conducted with participants that had completed active treatment for cancer within the previous 2 years. Participants were colorectal cancer survivors (N = 24, men = 11, women = 13, M age = 69.38 years, SD = 4.19) recruited from a private hospital in Perth, Australia on the basis that they had existing morbidities that put them at increased risk of cardiovascular disease. Interview transcripts were analyzed using thematic analysis. Five main themes emerged: back to normal; the pleasures in life: 'is it worth it?'; beliefs about health behavior; skepticism of eating guidelines; and lack of motivation. The majority of participants felt they were in good health and had made a full recovery. Participants questioned whether it was worth changing their lifestyle given their life stage and referred to the desire to enjoy life. Lay health beliefs, skepticism of eating guidelines, and a lack of motivation were barriers to change. Interventions should target lay beliefs and skepticism in relation to health behaviors in order to reinforce the importance and value of participating in health-related behavior. Findings may inform the development of effective, patient-centered interventions that target lay health beliefs and build motivation for health behavior change. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  15. Colorectal Cancer

    Science.gov (United States)

    ... 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 ...

  16. The Influence of Smoking, Gender, and Family History on Colorectal Adenomas

    Directory of Open Access Journals (Sweden)

    Tracy Onega

    2010-01-01

    Full Text Available Evidence independently links smoking, family history, and gender with increased risk of adenomatous polyps. Using data from the New Hampshire Colonoscopy Registry (2004–2006, we examined the relation of combined risk factors with adenoma occurrence in 5,395 individuals undergoing screening colonoscopy. Self-reported data on smoking, family history and other factors were linked to pathology reports identifying adenomatous polyps and modeled with multiple logistic regression. In adjusted models a >15 pack-year smoking history increased the likelihood of an adenoma (OR=1.54, 95% CI 1.28–1.86, although ≤15 pack-years did not (OR=1.07, 95% CI 0.87–1.32. Gender-stratified models showed a significantly increased risk of adenoma at lower smoking exposure even for men (OR=1.32; 95% CI:1.00–1.76, but not for women (OR=0.85; 95% CI:0.61–1.14. An ordered logistic regression model of adenoma occurrence showed a smoking history of ≥15 pack-years associated with 61% higher odds of adenoma at successively larger size categories (95% CI 1.34–1.93. For individuals with a family history of colorectal cancer, smoking does not further increase the risk of adenomas. Smoking duration is linked to occurrence and size of adenoma, especially for men.

  17. The influence of year-end bonuses on colorectal cancer screening.

    Science.gov (United States)

    Armour, Brian S; Friedman, Carol; Pitts, M Melinda; Wike, Jennifer; Alley, Linda; Etchason, Jeff

    2004-09-01

    To estimate the effect of physician bonus eligibility on colorectal cancer (CRC) screening, controlling for patient and primary care physician characteristics. Retrospective study using managed care plan claims data from 2000 and 2001. Data on 50-year-old commercially insured patients in a managed care health plan were linked to enrollment and provider files. The data included information on 6749 patients (3058 in 2000 and 3691 in 2001). Multivariate logistic regression models were used to assess the association between CRC screening receipt and physician bonus eligibility. From 2000 to 2001, CRC screening use increased from 23.4% to 26.4% (P analysis revealed that the probability that a patient received a CRC screening was approximately 3 percentage points higher in the bonus year, 2001 (P < .01). Bonuses targeted at individual physicians were associated with increased use of CRC screening tests. However, more research is needed to examine the effect of performance-based incentives on resource use and the quality of medical care. Specifically, there is a need to determine whether explicit financial incentives are effective in reducing racial disparities in the quality of patient care. This has particular relevance for CRC screening given that black patients are less likely to be screened, they have higher CRC incidence and mortality rates compared with other racial groups, and screening has been shown to be more cost effective in this population.

  18. The Influence of Smoking, Gender, and Family History on Colorectal Adenomas

    International Nuclear Information System (INIS)

    Onega, T.; Goodrich, M.; Dietrich, A.; Onega, T.; Goodrich, M.; Dietrich, A.; Butterly, L.; Butterly, L.

    2010-01-01

    Evidence independently links smoking, family history, and gender with increased risk of adenomatous polyps. Using data from the New Hampshire Colonoscopy Registry (2004-2006), we examined the relation of combined risk factors with adenoma occurrence in 5,395 individuals undergoing screening colonoscopy. Self-reported data on smoking, family history and other factors were linked to pathology reports identifying adenomatous polyps and modeled with multiple logistic regression. In adjusted models a >15 pack-year smoking history increased the likelihood of an adenoma (OR=1.54 , 95% CI 1.28-1.86), although ≤15 pack-years did not (OR=1.07, 95% CI 0.87-1.32). Gender-stratified models showed a significantly increased risk of adenoma at lower smoking exposure even for men ( OR = 1.32; 95% CI:1.00-1.76. but not for women (OR = 0.85; 95% CI:0.61-1.14). An ordered logistic regression model of adenoma occurrence showed a smoking history of ≥15 pack-years associated with 61% higher odds of adenoma at successively larger size categories (95% CI 1.34-1.93). For individuals with a family history of colorectal cancer, smoking does not further increase the risk of adenomas. Smoking duration is linked to occurrence and size of adenoma, especially for men.

  19. The Influence of Hospital Volume on Circumferential Resection Margin Involvement: Results of the Dutch Surgical Colorectal Audit.

    Science.gov (United States)

    Gietelink, Lieke; Henneman, Daniel; van Leersum, Nicoline J; de Noo, Mirre; Manusama, Eric; Tanis, Pieter J; Tollenaar, Rob A E M; Wouters, Michel W J M

    2016-04-01

    This population-based study evaluates the association between hospital volume and CRM (circumferential resection margin) involvement, adjusted for other confounders, in rectal cancer surgery. A low hospital volume (risk of CRM involvement (odds ratio=1.54; 95% CI: 1.12-2.11). To evaluate the association between hospital volume and CRM (circumferential resection margin) involvement in rectal cancer surgery. To guarantee the quality of surgical treatment of rectal cancer, the Association of Surgeons of the Netherlands has stated a minimal annual volume standard of 20 procedures per hospital. The influence of hospital volume has been examined for different outcome variables in rectal cancer surgery. Its influence on the pathological outcome (CRM) however remains unclear. As long-term outcomes are best predicted by the CRM status, this parameter is of essential importance in the debate on the justification of minimal volume standards in rectal cancer surgery. Data from the Dutch Surgical Colorectal Audit (2011-2012) were used. Hospital volume was divided into 3 groups, and baseline characteristics were described. The influence of hospital volume on CRM involvement was analyzed, in a multivariate model, between low- and high-volume hospitals, according to the minimal volume standards. This study included 5161 patients. CRM was recorded in 86% of patients. CRM involvement was 11% in low-volume group versus 7.7% and 7.9% in the medium- and high-volume group (P≤0.001). After adjustment for relevant confounders, the influence of hospital volume on CRM involvement was still significant odds ratio (OR) = 1.54; 95% CI: 1.12-2.11). The outcomes of this pooled analysis support minimal volume standards in rectal cancer surgery. Low hospital volume was independently associated with a higher risk of CRM involvement (OR = 1.54; 95% CI: 1.12-2.11).

  20. Colorectal Cancer Screening

    Science.gov (United States)

    ... Genetics of Colorectal Cancer Colorectal Cancer Screening Research Colorectal Cancer Screening (PDQ®)–Patient Version What is screening? Go ... These are called diagnostic tests . General Information About Colorectal Cancer Key Points Colorectal cancer is a disease in ...

  1. Colorectal Cancer Prevention

    Science.gov (United States)

    ... Genetics of Colorectal Cancer Colorectal Cancer Screening Research Colorectal Cancer Prevention (PDQ®)–Patient Version What is prevention? Go ... to keep cancer from starting. General Information About Colorectal Cancer Key Points Colorectal cancer is a disease in ...

  2. INFLUENCE OF THE FDG-PET/CT ON THE DIAGNOSE AND STAGING OF COLORECTAL CANCER.

    Directory of Open Access Journals (Sweden)

    Nikola Y. Kolev

    2012-06-01

    Full Text Available INTRODUCTION: In patients with colorectal cancer (CRC, preoperative evaluation and staging should focus on techniques that might alter the preoperative or intraoperative surgical plan. Conventional imaging methods (CT, MRI have low accuracy for identifying the depth of tumour infiltration and have limited ability to detect regional lymph node involvement. The aim of this study was to evaluate the utility of FDG-PET in the initial staging of patients with CC in comparison with conventional staging methods and to determine its impact on therapeutic management.METHODS: In First Clinic of Surgery at University Hospital “St. Marina” one hundred and four patients with a diagnosis of CRC (53 males and 51 females; mean age 66.76± 12.36 years, selected prospectively. All patients were studied for staging using a standard procedure (CT and FDG-PET. The reference method was histology. The effect of FDG-PET on the diagnose and the operative treatment was studied.RESULTS: In 14 patients, surgery was contraindicated by FDG-PET owing to the extent of disease (only 6/14 suspected by CT. FDG-PET revealed four synchronous tumours. For N staging, both procedures showed a relatively high specificity but a low diagnostic accuracy (PET 56%, CT 60% and sensitivity (PET 21%, CT 25%. For M assessment, diagnostic accuracy was 92% for FDGPET and 87% for CT. FDG-PET results led to modification of the therapy approach in 17.85% of the patients with rectal cancer and in 14.8% of the patients with colon cancer.CONCLUSION: Compared with conventional techniques, FDGPET appears to be useful in pre-surgical staging of CC, revealing unsuspected disease and impacting on the treatment approach.

  3. Influence of thymidylate synthase expression on survival in patients with colorectal cancer

    Directory of Open Access Journals (Sweden)

    Kinjal K Gajjar

    2017-01-01

    Full Text Available Background: Thymidylate synthase (TS plays a critical role in nucleotide metabolism and is an important target for 5-fluorouracil (5-FU, the standard chemotherapeutic drug for treatment of colorectal cancer (CRC. Aims and Methods: The present study aimed to evaluate TS variable number tandem repeat sequences (VNTR polymorphism by polymerase chain reaction and TS protein expression by immunohistochemistry and its association with clinicopathological parameters in untreated CRC patients (n = 100. Further, the prognostic and predictive role of TS has been evaluated. Results: For TS VNTR polymorphism, the observed frequencies of 2R/2R, 2R/3R, and 3R/3R genotypes were 22%, 51%, and 27%, respectively. When immunohistochemical localization was studied, cytoplasmic staining for TS was observed in 70% of patients. A significant inverse correlation was noted between TS protein expression and tumor, node, metastasis staging (P = 0.027, Dukes' staging (P = 0.039, and lymph node status (P = 0.012 of CRC patients. However, there was no significant correlation between TS VNTR polymorphism and TS protein expression. On survival analysis, a significantly shorter overall survival (OS was seen in CRC patients with negative protein expression (P = 0.031. Moreover, the subgroup of CRC patients treated only with surgery also showed a trend of poor OS in patients with negative TS protein expression (P = 0.058. However, neither TS polymorphism nor its protein expression was able to predict relapse-free survival. Conclusion: Negative TS protein expression may be related to unfavorable clinical outcome in CRC patients. However, further studies in a larger set of patients are necessary to better assess TS as a prognostic and predictive marker for 5-FU response in CRC patients.

  4. The influence of contextual factors on patient involvement during follow-up consultations after colorectal cancer surgery: a case study.

    Science.gov (United States)

    Thomsen, Thora G; Soelver, Lisbeth; Hølge-Hazelton, Bibi

    2017-11-01

    To identify the contextual factors that influence individual patient involvement during colorectal cancer surgical follow-up consultations. The healthcare system is subject to the requirement and expectation of greater involvement of patients and relatives. Increased patient involvement requires the development and implementation of new communication initiatives. Research shows that it is also necessary to consider the contextual circumstances surrounding patient involvement in specific situations. Case study of a single Danish outpatient clinic, which allows the issues and circumstances involved in an everyday situation to be captured. 12 nonparticipative observations of outpatient visits and, subsequently, seven in-depth patient interviews. Content analysis based on a dialogical, interactive framework, which underpinned the identification of current contextual factors. The results showed five contextual factors that seemed to have an impact on patient involvement. The first, 'Two dimensions of patient involvement: treatment-oriented and person-oriented' highlighted a dual interpretation of patient involvement in the consultation situation. The two dimensions seemed to be influenced by four additional factors: 'Doctors leading the agenda', 'Traditional health professional roles', 'Unclear responsibilities' and 'Guidance primarily focused on treatment'. The results showed how patient involvement in clinical practice could be understood as a two-way movement, in which patients are invited to participate in clinical practice, while health professionals are invited to participate in the patients' lives. The movement will change from situation to situation and is influenced by several contextual factors. The results can help doctors and nurses to navigate using a goal-oriented approach towards patient involvement. The study makes visible the need for research-based development of the independent role of the nursing profession in cancer care follow-up, with a view to

  5. The Prognostic Influence of BRAF Mutation and other Molecular, Clinical and Laboratory Parameters in Stage IV Colorectal Cancer.

    Science.gov (United States)

    Karadima, Maria L; Saetta, Angelica A; Chatziandreou, Ilenia; Lazaris, Andreas C; Patsouris, Efstratios; Tsavaris, Nikolaos

    2016-10-01

    Our aim was to evaluate the predictive and prognostic influence of BRAF mutation and other molecular, clinical and laboratory parameters in stage IV colorectal cancer (CRC). 60 patients were included in this retrospective analysis, and 17 variables were examined for their relation with treatment response and survival. KRAS mutation was identified in 40.3 % of cases, BRAF and PIK3CA in 8.8 % and 10.5 % respectively. 29.8 % of patients responded to treatment. Median survival time was 14.3 months. Weight loss, fever, abdominal metastases, blood transfusion, hypoalbuminaimia, BRAF and PIK3CA mutations, CRP and DNA Index were associated with survival. In multivariate analysis, male patients had 3.8 times higher probability of response, increased DNA Index was inversely correlated with response and one unit raise of DNA Index augmented 6 times the probability of death. Our findings potentiate the prognostic role of BRAF, PIK3CA mutations and ploidy in advanced CRC.

  6. Factors influencing delay in the diagnosis of colorectal cancer: a study protocol

    International Nuclear Information System (INIS)

    Esteva, Magdalena; Ramos, Maria; Cabeza, Elena; Llobera, Joan; Ruiz, Amador; Pita, Salvador; Segura, Josep M; Cortés, Jose M; González-Lujan, Luis

    2007-01-01

    Colorectal cancer (CRC) is the second most frequent tumor in developed countries. Since survival from CRC depends mostly on disease stage at the time of diagnosis, individuals with symptoms or signs suspicious of CRC should be examined without delay. Many factors, however, intervene between symptom onset and diagnosis. This study was designed to: 1) Describe the diagnostic process of CRC from the onset of first symptoms to diagnosis and treatment. 2) Establish the time interval from initial symptoms to diagnosis and treatment, globally and considering patient's and doctors' delay, with the latter due to family physician and/or hospital services. 3) Identify the factors related to defined types of delay. 4) Assess the concordance between information included in primary health care and hospital clinical records regarding onset of first symptoms. Descriptive study, coordinated, with 5 participant groups of 5 different Spanish regions (Balearic Islands, Galicia, Catalunya, Aragón and Valencia Health Districts), with a total of 8 acute public hospitals and 140 primary care centers. Incident cases of CRC during the study period, as identified from pathology services at the involved hospitals. A sample size of 896 subjects has been estimated, 150 subjects for each participant group. Information will be collected through patient interviews and primary health care and hospital clinical records. Patient variables will include sociodemographic variables, family history of cancer, symptom perception, and confidence in the family physician; tumor variables will include tumor site, histological type, grade and stage; symptom variables will include date of onset, type and number of symptoms; health system variables will include number of patient contacts with family physician, type and content of the referral, hospital services attending the patient, diagnostic modalities and results; and delay intervals, including global delays and delays attributed to the patient

  7. Influence of K-ras status and anti-tumour treatments on complications due to colorectal self-expandable metallic stents: a retrospective multicentre study.

    Science.gov (United States)

    Fuccio, Lorenzo; Correale, Loredana; Arezzo, Alberto; Repici, Alessandro; Manes, Gianpiero; Trovato, Cristina; Mangiavillano, Benedetto; Manno, Mauro; Cortelezzi, Claudio Camillo; Dinelli, Marco; Cennamo, Vincenzo; de Bellis, Mario

    2014-06-01

    This study aimed to explore the relationship between K-ras status, anti-tumour treatments, and the complications of colorectal self-expandable metallic stenting in colorectal cancer. This is a retrospective, multicentre study of 91 patients with obstructive advanced colorectal cancer palliated with enteral stents between 2007 and 2011. K-ras wild-type tumours were diagnosed in 44 patients (48.4%); 82 (90.1%) received chemotherapy and 45 (49.4%) had additional biological therapy (34 bevacizumab, 11 cetuximab). Twenty-one (23.1%) experienced stent-related complications: 11 (52.4%) occurred in the K-ras mutant group (P=0.9). K-ras wild-type patients were not less likely to develop adverse events than K-ras mutant patients (OR, 0.99; 95% CI: 0.4-2.7). Overall mean time to complication was 167.6 days (range 4-720 days), with no difference between the two groups (141 vs. 197 days; P=0.5). Chemotherapy did not influence the risk of complications (OR, 0.56; 95% CI: 0.14-2.9), and there was no evidence that patients treated with chemotherapy and cetuximab were more likely to experience stent-related complications than patients treated with chemotherapy alone, or untreated (OR, 1.2; 95% CI: 0.2-5.9). Although perforation rates were higher with bevacizumab-based treatment (11.8% vs. 7%), this result was not statistically significant (P=0.69). K-ras mutation status, chemotherapy, and biological treatments should not influence colorectal stent-related complication rates. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  8. Effects of cyclic-nucleotide derivatives on the growth of human colonic carcinoma xenografts and on cell production in the rat colonic crypt epithelium.

    Science.gov (United States)

    Tutton, P J; Barkla, D H

    1981-08-01

    Previous studies have shown that various amine hormones are able to influence the growth rate of human colorectal carcinomas propagated as xenografts in immune-deprived mice, and it is now well known that the effects of many amine and other hormones are mediated by cyclic nucleotides, acting as second messengers within cells. In the present study the influence of various derivatives of cyclic adenosine monophosphate and cyclic guanosine monophosphate on the growth of two different lines of colorectal cancer growing in immune-deprived mice, and on the cell production rate in the colonic crypt epithelium of the rat, was assessed. Growth of each tumour line, as well as crypt-cell production, was suppressed by treatment wit N6O2' dibutyryl and N6 monobutyryl derivatives of cyclic adenosine monophosphate. Dibutyryl cyclic guanosine monophosphate, on the other hand, was found to promote the growth of Tumour HXK4 and to promote crypt cell production, but to have no significant effect on Tumour HXM2.

  9. The Influence of Husbands' or Male Partners' Support on Women's Psychosocial Adjustment to Having an Ostomy Resulting from Colorectal Cancer

    Science.gov (United States)

    Altschuler, Andrea; Ramirez, Michelle; Grant, Marcia; Wendel, Christopher; Hornbrook, Mark C.; Herrinton, Lisa; Krouse, Robert S.

    2009-01-01

    Objective Some patients with colorectal cancer (CRC) require a permanent ostomy, which changes bodily function and can create psychosocial distress. However, little is known about the influence of men's support on women's psychosocial adjustment to having an ostomy as a result of CRC. Methods Participants initially completed the City of Hope-CRC Quality of Life questionnaire. We then conducted in-depth interviews with 30 female participants. Interview questions focused on body image, gender, and sexuality. Interviews were recorded and transcribed. We used qualitative methods to analyze the interview data and compared global HRQOL quartile scores to the overall ways that women discussed husbands' or partners' support regarding psychosocial adjustments to having ostomies. Results Of 30 participants, 22 were married or partnered at the time of surgery and 8 were single. The non-partnered respondents are not included in this analysis. Of the 22 married/partnered women, 17 described positive support from husbands being central to their psychosocial adjustment, 3 described a lack or withdrawal of support negatively affecting adjustment, and 2 described support as neither positive nor negative. In 17 cases, women's high or low quantitative HRQOL scores matched the positive or negative qualitative findings. There were 3 cases in which there were positive qualitative data and low HRQOL scores, but each of these cases, women reported serious current co-morbidities. Conclusions These findings suggest that the provision or withdrawal of husbands' or partners' support can have a considerable impact on the psychosocial adjustment of female CRC patients with ostomies. These findings appear to be both short- and long-term. Survivorship assessments should include appraisals of women's relationships to spouses/partners. PMID:19448512

  10. The influence of husbands' or male partners' support on women's psychosocial adjustment to having an ostomy resulting from colorectal cancer.

    Science.gov (United States)

    Altschuler, Andrea; Ramirez, Michelle; Grant, Marcia; Wendel, Christopher; Hornbrook, Mark C; Herrinton, Lisa; Krouse, Robert S

    2009-01-01

    Some patients with colorectal cancer (CRC) require a permanent ostomy, which changes bodily function and can create psychosocial distress. However, little is known about the influence of men's support on women's psychosocial adjustment to having an ostomy as a result of CRC. Participants initially completed the City of Hope-CRC Quality of Life questionnaire. We then conducted in-depth interviews with 30 female participants. Interview questions focused on body image, gender, and sexuality. Interviews were recorded and transcribed. We used qualitative methods to analyze the interview data and compared global health-related quality of life (HRQOL) quartile scores to the overall ways that women discussed husbands' or partners' support regarding psychosocial adjustments to having ostomies. Of 30 participants, 22 were married or partnered at the time of surgery and 8 were single. The nonpartnered respondents are not included in this analysis. Of the 22 married/partnered women, 17 described positive support from husbands being central to their psychosocial adjustment, 3 described a lack or withdrawal of support negatively affecting adjustment, and 2 described support as neither positive nor negative. In 17 cases, women's high or low quantitative HRQOL scores matched the positive or negative qualitative findings. There were 3 cases in which there were positive qualitative data and low HRQOL scores, but in each of these cases, women reported serious current comorbidities. These findings suggest that the provision or withdrawal of husbands' or partners' support can have a considerable impact on the psychosocial adjustment of female CRC patients with ostomies. These findings appear to be both short term and long term. Survivorship assessments should include appraisals of women's relationships to their spouses/partners.

  11. An apple oligogalactan enhances the growth inhibitory effect of 5-fluorouracil on colorectal cancer.

    Science.gov (United States)

    Li, Yuhua; Fan, Lei; Niu, Yinbo; Mian, Wenguang; Zhang, Feng; Xie, Ming; Sun, Yang; Mei, Qibing

    2017-06-05

    Treatment of colorectal cancer (CRC) remains a clinical challenge, since current therapies are associated with obvious side effects and high expenses. These limitations highlight an urgent need for developing novel and safe treatment strategies. It is suggested that combinatorial strategies could be more effective and much safer than monotherapy in cancer treatment. In our previous study, an apple oligogalactan (AOG) has been found to show beneficial effect on treating CRC. This study tried to investigate whether AOG could enhance the growth inhibitory effect of 5-FU in human CRC cells (HT-29 and SW-620), a mouse model of colitis associated colorectal cancer and a murine model of xenograft tumor. The IC 50 values of 5-FU were 26.70±0.21μM in HT-29 cells and 26.71±2.06μM in SW-620 cells. Pretreatment with 0.05 or 0.1mM AOG down-regulated IC 50 values of 5-FU to 22.44±1.01 or 18.67±1.16μM in HT-29 and 21.21±1.49 or 17.99±1.42μM in SW-620 cells. AOG enhanced 5-FU-induced cell apoptosis and S phase arrest. The combination not only protected ICR mice against intestinal toxicities and carcinogenesis induced by 1,2-dimethylhydrazine and dextran sodium sulfate, but also decreased the xenograft tumor size, triggered apoptosis and inhibited proliferation of tumor cells in nude mice. The mechanisms of AOG on enhancing the growth inhibitory effect of 5-FU may be through the influence of TLR-4/NF-κB pathway. Taken together, the combinatorial therapy using AOG and 5-FU is a promising strategy for the treatment of colorectal cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Influence of preoperative peripheral parenteral nutrition with micronutrients after colorectal cancer patients.

    Science.gov (United States)

    Liu, Ming-Yi; Tang, Hsiu-Chih; Hu, Shu-Hui; Yang, Hui-Lan; Chang, Sue-Joan

    2015-01-01

    The inflammatory reactions are stronger after surgery of malnourished preoperative patients. Many studies have shown vitamin and trace element deficiencies appear to affect the functioning of immune cells. Enteral nutrition is often inadequate for malnourished patients. Therefore, total parenteral nutrition (TPN) is considered an effective method for providing preoperative nutritional support. TPN needs a central vein catheter, and there are more risks associated with TPN. However, peripheral parenteral nutrition (PPN) often does not provide enough energy or nutrients. This study investigated the inflammatory response and prognosis for patients receiving a modified form of PPN with added fat emulsion infusion, multiple vitamins (MTV), and trace elements (TE) to assess the feasibility of preoperative nutritional support. Methods. A cross-sectional design was used to compare the influence of PPN with or without adding MTV and TE on malnourished abdominal surgery patients. Both preoperative groups received equal calories and protein, but due to the lack of micronutrients, patients in preoperative Group B exhibited higher inflammation, lower serum albumin levels, and higher anastomotic leak rates and also required prolonged hospital stays. Malnourished patients who receive micronutrient supplementation preoperatively have lower postoperative inflammatory responses and better prognoses. PPN with added fat emulsion, MTV, and TE provides valid and effective preoperative nutritional support.

  13. Colorectal signet ring cell carcinoma: Influence of EGFR, E-cadherin and MMP-13 expression on clinicopathological features and prognosis.

    Science.gov (United States)

    Foda, Abd Al-Rahman Mohammad; Aziz, Azza Abdel; Mohamed, Mie Ali

    2018-02-01

    Signet ring cell carcinoma (SRCC) is unique rare subtype of mucin-producing colorectal adenocarcinoma characterized by presence of signet ring cells, in >50% of the tumor tissue. This study aims to investigate expression of EGFR, E-cadherin and MMP-13 expression on clinicopathological features of signet ring cell type and its prognostic effect using manual tissue microarray technique. In this work, we studied tumor tissue specimens from 150 patients with colorectal cancer cases among which 19 cases of SRCC. High density manual tissue microarrays were constructed using modified mechanical pencil tips technique and immunohistochemistry for EGFR, E-cadherin and MMP-13 expression was done. We found that SRCC was significantly associated with younger age and more frequency of LN metastasis than all other groups. SRCC was also significantly associated with annular gross picture, more depth of invasion, advanced stage, more lymphovascular emboli, more perineural invasion and less arousal from an overlying adenoma. In conclusion, colorectal SRCC has distinctive clinicopathological and histological features with different unique mechanisms of carcinogenesis and more aggressive biologic behavior than other colorectal carcinoma subtypes. Negative/low expressions of EGFR and E-cadherin and MMP-13 were found in SRCC with no effect on the prognosis. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Measuring the importance of attributes that influence consumer attitudes to colorectal cancer screening.

    Science.gov (United States)

    Salkeld, Glenn P; Solomon, Michael J; Short, Leonie; Ward, Jeanette

    2003-03-01

    The aim of the present study was to rate the importance of attributes of screening for bowel cancer. Randomly selected households in central Sydney were contacted to identify men and women aged 50-70 years who were then asked to complete a self-administered questionnaire about bowel cancer screening and related issues. Seven hundred and ninety-one residents (362 men and 429 women) returned questionnaires. Respondents were asked to rate the extent to which each of 34 attributes would encourage them to participate in bowel cancer screening. The three most highly rated attributes were: if the test was recommended by their general practitioner (GP; 94% either 'strongly agreed' or 'agreed'); if the test identified early cancers (92%); and if the test would avert a premature death due to bowel cancer (90%). Having a friend or relative with bowel cancer (61%), advertising (41%) or famous people promoting the program (62%) were less influential. Respondents who were unemployed or on a pension were less likely to participate in screening than those who were employed if there was an 'out of pocket' charge of 15.00 Australian dollars (chi 2 = 7.56, 2df, P = 0.006). Respondents with higher levels of education were significantly more concerned than respondents with lower levels of education about test accuracy (chi 2 = 15.76, 2df, P < 0.001), its availability from their local chemist (chi 2 = 16.96, 2df, P < 0.001), being able to return the test kit by post (chi 2 = 21.9, 2df, P < 0.001) or deposit it with their local chemist (chi 2 = 10.0, 2df, P < 0.01). They were also less likely to be influenced by a famous person promoting bowel cancer screening (chi 2 = 18.87, 2df, P < 0.001). Our results endorse the role of the GP in bowel cancer screening. However, the study also has demonstrated that test accuracy, the convenience of the screening service and notification of test results are valued differently by subgroups in the community, according to their level of education.

  15. The influence of Aloe vera and xenograft XCB toward of bone morpho protein 2 BMP2 expression and amount of osteoblast of alveolar bone induced into tooth extraction sockets Cavia cobaya

    Directory of Open Access Journals (Sweden)

    Utari Kresnoadi

    2014-12-01

    Full Text Available Tooth extraction can cause inflammation leading to alveolar ridge resorption. In addition, prominent ridge has crucial role for making denture su-ccessfully. Thus, socket preservation is needed to prevent greater alveolar ridge resorption. An innovative material, a combination of Aloe vera and xe-nograft (XCB, is then considered as a biogenic stimulator that can reduce inflammation, as a result, the growth of alveolar bone is expected to be impro-ved. This research is aimed to prove whether the mixture of Aloe vera and xenograft can stimulate BMP2 and increase osteoblasts. Forty-eight Cavia co-baya animals were divided into eight groups each of which consisted of six animals. The mandibular incisors of those Cavia cobaya animals were then extracted and filled with PEG as Group Control, XCB as Group XCB, Aloe vera as Group Aloe vera, and a combination of Aloe vera +XCB as Group Aloe vera +XCB. Next, the first four groups were sacrificed seven days after extraction, and the second four groups were sacrificed 30 days after extrac-tion. And then, immunohistochemical and histopathology examinations were conducted to examine BMP2 expression and osteoblasts. Based on the re-sult known that the mixture of Aloe vera and xenograft can increase BMP2 expression and amount of osteoblasts. It can be concluded that the mixture of Aloe vera and xenograft can increase BMP2 expression and amount of osteoblast cel . It can be used as an alternative material to increase the growth of alveolar bone after extraction.

  16. Colorectal tuberculosis

    International Nuclear Information System (INIS)

    Nagi, B.; Kochhar, R.; Bhasin, D.K.; Singh, K.

    2003-01-01

    Our objective was to evaluate the incidence of colorectal tuberculosis in our series and to study its radiological spectrum. A total of 684 cases of proven gastrointestinal tuberculosis with positive barium contrast findings seen over a period of more than one decade were evaluated. The study did not include cases where colon was involved in direct contiguity with ileo-caecal tuberculosis. Seventy-four patients (10.8%) had colorectal tuberculosis. Commonest site involved was transverse colon, closely followed by rectum and ascending colon. Radiological findings observed were in the form of strictures (54%), colitis (39%) and polypoid lesions (7%). Complications noted were in the form of perforations and fistulae in 18.9% of cases. Colorectal tuberculosis is a very common site for gastrointestinal tuberculosis. Typical findings of colorectal tuberculosis are strictures, signs of colitis and polypoid lesions. Common complications are perforation and fistulae. (orig.)

  17. Colorectal Cancer

    Science.gov (United States)

    ... possible. Research will help us better understand whether chemotherapy can benefit elderly colorectal cancer patients. Such patients often do not receive chemotherapy due to concerns about side effects. We will ...

  18. The influence of survivin shRNA on the cell cycle and the invasion of SW480 cells of colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Yu Jin

    2008-07-01

    Full Text Available Abstract Background The objective was to understand the influence of Survivin plasmid with short hairpin RNA (shRNA on the cell cycle, invasion, and the silencing effect of Survivin gene in the SW480 cell of colorectal carcinoma. Methods A eukaryotic expression vector, PGCH1/Survivin shRNA, a segment sequence of Survivin as target, was created and transfected into colorectal carcinoma cell line SW480 by the non-lipid method. The influence on the Survivin protein was analyzed by Western blotting, while the cell cycle, cell apoptosis were analyzed by flow cytometry, and invasion of the cell was analyzed by Transwell's chamber method. Results After the transfection of PGCH1/Survivin shRNA, the expression of Survivin protein in SW480 cells was dramatically decreased by 60.68%, in which the cells were stopped at G2/M phase, even though no apoptosis was detected. The number of transmembranous cells of the experimental group, negative control group, and blank control group were 14.46 ± 2.11, 25.12 ± 8.37, and 25.86 ± 7.45, respectively (P 0.05. Conclusion Survivin shRNA could significantly reduce the expression of Survivin protein and invasion of SW480 cells. Changes in cell cycle were observed, but no apoptosis was induced.

  19. Nutritional status assessment in colorectal cancer patients

    OpenAIRE

    Joana Pedro Lopes; Paula Manuela de Castro Cardoso Pereira; Ana Filipa dos Reis Baltazar Vicente; Alexandra Bernardo; María Fernanda de Mesquita

    2013-01-01

    The present study intended to evaluate the nutritional status of Portuguese colorectal patients and associated it with surgery type as well as quality of life outcomes. Malnutrition can affect up to 85% of cancer patients and specifically 30-60% in colorectal cancer and can significantly influence health outcomes. A sample of 50 colorectal cancer patients was evaluated in what refers to several anthropometric measures, food intake, clinical history, complications rate before and after surgery...

  20. Comparison of Two Xenograft Materials Used in Sinus Lift Procedures: Material Characterization and In Vivo Behavior

    Directory of Open Access Journals (Sweden)

    María Piedad Ramírez Fernández

    2017-06-01

    Full Text Available Detailed information about graft material characteristic is crucial to evaluate their clinical outcomes. The present study evaluates the physico-chemical characteristics of two xenografts manufactured on an industrial scale deproteinized at different temperatures (non-sintered and sintered in accordance with a protocol previously used in sinus lift procedures. It compares how the physico-chemical properties influence the material’s performance in vivo by a histomorphometric study in retrieved bone biopsies following maxillary sinus augmentation in 10 clinical cases. An X-ray diffraction analysis revealed the typical structure of hydroxyapatite (HA for both materials. Both xenografts were porous and exhibited intraparticle pores. Strong differences were observed in terms of porosity, crystallinity, and calcium/phosphate. Histomorphometric measurements on the bone biopsies showed statistically significant differences. The physic-chemical assessment of both xenografts, made in accordance with the protocol developed on an industrial scale, confirmed that these products present excellent biocompatibilitity, with similar characteristics to natural bone. The sintered HA xenografts exhibited greater osteoconductivity, but were not completely resorbable (30.80 ± 0.88% residual material. The non-sintered HA xenografts induced about 25.92 ± 1.61% of new bone and a high level of degradation after six months of implantation. Differences in the physico-chemical characteristics found between the two HA xenografts determined a different behavior for this material.

  1. Risks of Colorectal Cancer Screening

    Science.gov (United States)

    ... Genetics of Colorectal Cancer Colorectal Cancer Screening Research Colorectal Cancer Screening (PDQ®)–Patient Version What is screening? Go ... These are called diagnostic tests . General Information About Colorectal Cancer Key Points Colorectal cancer is a disease in ...

  2. Vitrification and xenografting of human ovarian tissue.

    Science.gov (United States)

    Amorim, Christiani Andrade; Dolmans, Marie-Madeleine; David, Anu; Jaeger, Jonathan; Vanacker, Julie; Camboni, Alessandra; Donnez, Jacques; Van Langendonckt, Anne

    2012-11-01

    To assess the efficiency of two vitrification protocols to cryopreserve human preantral follicles with the use of a xenografting model. Pilot study. Gynecology research unit in a university hospital. Ovarian biopsies were obtained from seven women aged 30-41 years. Ovarian tissue fragments were subjected to one of three cryopreservation protocols (slow freezing, vitrification protocol 1, and vitrification protocol 2) and xenografted for 1 week to nude mice. The number of morphologically normal follicles after cryopreservation and grafting and fibrotic surface area were determined by histologic analysis. Apoptosis was assessed by the TUNEL method. Morphometric analysis of TUNEL-positive surface area also was performed. Follicle proliferation was evaluated by immunohistochemistry. After xenografting, a difference was observed between the cryopreservation procedures applied. According to TUNEL analysis, both vitrification protocols showed better preservation of preantral follicles than the conventional freezing method. Moreover, histologic evaluation showed a significantly higher proportion of primordial follicles in vitrified (protocol 2)-warmed ovarian tissue than in frozen-thawed tissue. The proportion of growing follicles and fibrotic surface area was similar in all groups. Vitrification procedures appeared to preserve not only the morphology and survival of preantral follicles after 1 week of xenografting, but also their ability to resume folliculogenesis. In addition, vitrification protocol 2 had a positive impact on the quiescent state of primordial follicles after xenografting. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  3. Hepatic resection for colorectal liver metastases. Influence on survival of preoperative factors and surgery for recurrences in 80 patients.

    Science.gov (United States)

    Nordlinger, B; Quilichini, M A; Parc, R; Hannoun, L; Delva, E; Huguet, C

    1987-01-01

    This report analyses an experience with 80 liver resections for metastatic colorectal carcinoma. Primary colorectal cancers had all been resected. Liver metastases were solitary in 44 patients, multiple in 36 patients, unilobar in 76 patients, and bilobar in 4 patients. Tumor size was less than 5 cm in 33 patients, 5-10 cm in 30 patients, and larger than 10 cm in 17 patients. There were 43 synchronous and 37 metachronous liver metastases with a delay of 2-70 months. The surgical procedures included more major liver resections (55 patients) than wedge resections (25 patients). Portal triad occlusion was used in most cases, and complete vascular exclusion of the liver was performed for resection of the larger tumors. In-hospital mortality rate was 5%. Three- and 5-year survival rates were 40.5% and 24.9%, respectively. None of the analysed criteria: size and number of liver metastases, delay after diagnosis of the primary cancer, Duke's stage, could differentiate long survivors from patients who did not benefit much from liver surgery due to early recurrence. Recurrences were observed in 51 patients during the study, two thirds occurring during the first year after liver surgery. Eight patients had resection of "secondary" metastases after a first liver resection: two patients for extrahepatic recurrences and six patients for liver recurrences. Encouraging results raise the question of how far agressive surgery for liver metastases should go. PMID:3827361

  4. Sulindac Sulfide, but Not Sulindac Sulfone, Inhibits Colorectal Cancer Growth

    Directory of Open Access Journals (Sweden)

    Christopher S. Williams

    1999-06-01

    Full Text Available Sulindac sulfide, a metabolite of the nonsteroidal antiinflammatory drug (NSAID sulindac sulfoxide, is effective at reducing tumor burden in both familial adenomatous polyposis patients and in animals with colorectal cancer. Another sulindac sulfoxide metabolite, sulindac sulfone, has been reported to have antitumor properties without inhibiting cyclooxygenase activity. Here we report the effect of sulindac sulfone treatment on the growth of colorectal carcinoma cells. We observed that sulindac sulfide or sulfone treatment of HCA-7 cells led to inhibition of prostaglandin E2 production. Both sulindac sulfide and sulfone inhibited HCA-7 and HCT-116 cell growth in vitro. Sulindac sulfone had no effect on the growth of either HCA-7 or HCT-116 xenografts, whereas the sulfide derivative inhibited HCA-7 growth in vivo. Both sulindac sulfide and sulfone inhibited colon carcinoma cell growth and prostaglandin production in vitro, but sulindac sulfone had no effect on the growth of colon cancer cell xenografts in nude mice.

  5. Reciprocal influence of B cells and tumor macro and microenvironments in the ApcMin/+ model of colorectal cancer.

    Science.gov (United States)

    Mion, Francesca; Vetrano, Stefania; Tonon, Silvia; Valeri, Viviana; Piontini, Andrea; Burocchi, Alessia; Petti, Luciana; Frossi, Barbara; Gulino, Alessandro; Tripodo, Claudio; Colombo, Mario P; Pucillo, Carlo E

    2017-01-01

    One of the most fascinating aspects of the immune system is its dynamism, meant as the ability to change and readapt according to the organism needs. Following an insult, we assist to the spontaneous organization of different immune cells which cooperate, locally and at distance, to build up an appropriate response. Throughout tumor progression, adaptations within the systemic tumor environment, or macroenvironment, result in the promotion of tumor growth, tumor invasion and metastasis to distal organs, but also to dramatic changes in the activity and composition of the immune system. In this work, we show the changes of the B-cell arm of the immune system following tumor progression in the Apc Min/+ model of colorectal cancer. Tumor macroenvironment leads to an increased proportion of total and IL-10-competent B cells in draining LNs while activates a differentiation route that leads to the expansion of IgA + lymphocytes in the spleen and peritoneum. Importantly, serum IgA levels were significantly higher in Apc Min/+ than Wt mice. The peculiar involvement of IgA response in the adenomatous transformation had correlates in the gut-mucosal compartment where IgA-positive elements increased from normal mucosa to areas of low grade dysplasia while decreasing upon overt carcinomatous transformation. Altogether, our findings provide a snapshot of the tumor education of B lymphocytes in the Apc Min/+ model of colorectal cancer. Understanding how tumor macroenvironment affects the differentiation, function and distribution of B lymphocytes is pivotal to the generation of specific therapies, targeted to switching B cells to an anti-, rather than pro-, tumoral phenotype.

  6. The Impact of Anesthesia-Influenced Process Measure Compliance on Length of Stay: Results From an Enhanced Recovery After Surgery for Colorectal Surgery Cohort.

    Science.gov (United States)

    Grant, Michael C; Pio Roda, Claro M; Canner, Joseph K; Sommer, Philip; Galante, Daniel; Hobson, Deborah; Gearhart, Susan; Wu, Christopher L; Wick, Elizabeth

    2018-05-17

    Process measure compliance has been associated with improved outcomes in enhanced recovery after surgery (ERAS) programs. Herein, we sought to assess the impact of compliance with measures directly influenced by anesthesiology in an ERAS for colorectal surgery cohort. From January 2013 to April 2015, data from 1140 consecutive patients were collected for all patients before (pre-ERAS) and after (ERAS) implementation of an ERAS program. Compliance with 9 specific process measures directly influenced by the anesthesiologist or acute pain service was analyzed to determine the impact on hospital length of stay (LOS). Process measure compliance was associated with a stepwise reduction in LOS. Patients who received >4 process measures (high compliance) had a significantly shorter LOS (incident rate ratio [IRR], 0.77; 95% CI, 0.70-0.85); P process measures) counterparts. Multivariable regression suggests that utilization of multimodal nausea and vomiting prophylaxis (IRR, 0.78; 95% CI, 0.68-0.89; P process measures directly influenced by the anesthesiologists and in concert with a formal anesthesia protocol is associated with reduced LOS. Engaging anesthesiology colleagues throughout the surgical encounter increases the overall value of perioperative care.

  7. Colorectal cancer

    International Nuclear Information System (INIS)

    Akiba, Suminori

    1992-01-01

    This paper describes colorectal cancer risk in relation to A-bomb radiation. The RERF Life Span Study has revealed the incidence of colorectal cancer to be significantly high in the group of A-bomb survivors than the control group. With regard to relative risk or excess relative risk, there is no definitive difference among sites in the colon. Risk for colon cancer is found to be linearly increased with increasing radiation doses, and in younger A-bomb survivors at the time of exposure. Risk associated with one Gy is estimated to be increased by double. There is no definitive variation between sex and between Hiroshima and Nagasaki. Excess relative risk would be increased rapidly with aging in the whole group of A-bomb survivors and with the cancer-prone age in younger A-bomb survivors at the time of exposure. (N.K.)

  8. Tumor p-glycoprotein correlates with efficacy of PF-3758309 in in vitro and in vivo models of colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Erica Lynn Bradshaw-Pierce

    2013-03-01

    Full Text Available P-glycoprotein (P-gp, a member of the ATP-binding cassette transporter family, is overexpressed in a number of different cancers and some studies show that P-gp overexpression can be correlated to poor prognosis or therapeutic resistance. Here we sought to elucidate if PF-3758309 (PF-309, a novel p-21 activated kinase inhibitor, efficacy was influenced by tumor P-gp. Based on in vitro proliferation data, a panel of colorectal cancer cell lines were ranked as sensitive or resistant and ABCB1 (P-gp expression was evaluated by microarray for these cell lines. P-gp expression was determined by western blot and activity determined by rhodamine efflux assay. Knock down of P-gp and pharmacologic inhibition of P-gp to restore PF-309 activity was performed in vitro. PF-309 activity was evaluated in vivo in cell line xenograft models and in primary patient derived tumor xenografts (PDTX. Mice were treated with 25 mg/kg PF-309 orally, twice daily. On the last day of treatment, tumor and plasma were collected for PF-309 analysis. Here we show that ABCB1 gene expression correlates with resistance to PF-309 treatment in vitro and the expression and activity of P-gp was verified in a panel of resistant cells. Furthermore, inhibition of P-gp increased the sensitivity of resistant cells, resulting in a 4-100 fold decrease in the IC50s. Eleven cell line xenografts and 12 PDTX models were treated with PF-309. From the cell line xenografts, we found a significant correlation between ABCB1 gene expression profiles and tumor response. We evaluated tumor and plasma concentrations for 8 tumor models (3 cell line xenografts and 5 PDTX models and a significant correlation was found between tumor concentration and response. Additionally, we show that tumor concentration is approximately 4-fold lower in tumors that express P-gp, verified by western blot. Our in vitro and in vivo data strongly suggests that PF-309 efficacy is influenced by the expression of tumor P-gp.

  9. Influence of Transfusions on Perioperative and Long-Term Outcome in Patients Following Hepatic Resection for Colorectal Metastases

    Science.gov (United States)

    Kooby, David A.; Stockman, Jennifer; Ben-Porat, Leah; Gonen, Mithat; Jarnagin, William R.; Dematteo, Ronald P.; Tuorto, Scott; Wuest, David; Blumgart, Leslie H.; Fong, Yuman

    2003-01-01

    Objective To determine if transfusion affected perioperative and long-term outcome in patients undergoing liver resection for metastatic colorectal cancer. Summary Background Data Blood transfusion produces host immunosuppression and has been postulated to result in adverse outcome for patients undergoing surgical resection of malignancies. Methods Blood transfusion records and clinical outcomes for 1,351 patients undergoing liver resection at a tertiary cancer referral center were analyzed. Results Blood transfusion was associated with adverse outcome after liver resection. The greatest effect was in the perioperative course, where transfusion was an independent predictor of operative mortality, complications, major complications, and length of hospital stay. This effect was dose-related. Patients receiving one or two units or more than two units had an operative mortality of 2.5% and 11.1%, respectively, compared to 1.2% for patients not requiring transfusions. Transfusion was also associated with adverse long-term survival by univariate analysis, but this factor was not significant on multivariate analysis. Even patients receiving only one or two units had a more adverse outcome. Conclusions Perioperative blood transfusion is a risk factor for poor outcome after liver resection. Blood conservation methods should be used to avoid transfusion, especially in patents currently requiring limited amounts of transfused blood products. PMID:12796583

  10. Get Tested for Colorectal Cancer

    Science.gov (United States)

    ... Print This Topic En español Get Tested for Colorectal Cancer Browse Sections The Basics Overview What to Expect ... section Overview 2 of 6 sections The Basics: Colorectal Cancer What is colorectal cancer? Colorectal cancer is a ...

  11. Influence of DPYD Genetic Polymorphisms on 5-Fluorouracil Toxicities in Patients with Colorectal Cancer: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Qiang Li

    2014-01-01

    Full Text Available Our meta-analysis aggregated existing results from relevant studies to comprehensively investigate the correlations between genetic polymorphisms in dihydropyrimidine dehydrogenase (DPYD gene and 5-fluorouracil (5-FU toxicities in patients with colorectal cancer (CRC. The MEDLINE (1966∼2013, the Cochrane Library Database (Issue 12, 2013, EMBASE (1980∼2013, CINAHL (1982∼2013, Web of Science (1945∼2013, and the Chinese Biomedical Database (CBM (1982∼2013 were searched without language restrictions. Meta-analyses were conducted with the use of STATA software (Version 12.0, Stata Corporation, College Station, TX, USA. Seven clinical cohort studies with a total of 946 CRC patients met our inclusion criteria, and NOS scores of each of the included studies were ≥5. Our findings showed that DPYD genetic polymorphisms were significantly correlated with high incidences of 5-FU-related toxicity in CRC patients. SNP-stratified analysis indicated that there were remarkable connections of IVS14+1G>A, 464T>A, and 2194G>A polymorphisms with the incidence of marrow suppression in CRC patients receiving 5-FU chemotherapy. Furthermore, we found that IVS14+1G>A, 496A>G, and 2194G>A polymorphisms were correlated with the incidence of gastrointestinal reaction. Ethnicity-stratified analysis also revealed that DPYD genetic polymorphisms might contribute to the development of marrow suppression and gastrointestinal reaction among Asians, but not among Caucasians. The present meta-analysis suggests that DPYD genetic polymorphisms may be correlated with the incidence of 5-FU-related toxicity in CRC patients.

  12. 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.

  13. Methodological considerations for disentangling a risk factor's influence on disease incidence versus postdiagnosis survival: The example of obesity and breast and colorectal cancer mortality in the Women's Health Initiative.

    Science.gov (United States)

    Cespedes Feliciano, Elizabeth M; Prentice, Ross L; Aragaki, Aaron K; Neuhouser, Marian L; Banack, Hailey R; Kroenke, Candyce H; Ho, Gloria Y F; Zaslavsky, Oleg; Strickler, Howard D; Cheng, Ting-Yuan David; Chlebowski, Rowan T; Saquib, Nazmus; Nassir, Rami; Anderson, Garnet; Caan, Bette J

    2017-12-01

    Often, studies modeling an exposure's influence on time to disease-specific death from study enrollment are incorrectly interpreted as if based on time to death from disease diagnosis. We studied 151,996 postmenopausal women without breast or colorectal cancer in the Women's Health Initiative with weight and height measured at enrollment (1993-1998). Using Cox regression models, we contrast hazard ratios (HR) from two time-scales and corresponding study subpopulations: time to cancer death after enrollment among all women and time to cancer death after diagnosis among only cancer survivors. Median follow-up from enrollment to diagnosis/censoring was 13 years for both breast (7,633 cases) and colorectal cancer (2,290 cases). Median follow-up from diagnosis to death/censoring was 7 years for breast and 5 years for colorectal cancer. In analyses of time from enrollment to death, body mass index (BMI) ≥ 35 kg/m 2 versus 18.5-cancer mortality: HR = 1.99; 95% CI: 1.54, 2.56 for breast cancer (p trend colorectal cancer (p trend = 0.05). However, in analyses of time from diagnosis to cancer death, trends indicated no significant association (for BMI ≥ 35 kg/m 2 , HR = 1.25; 95% CI: 0.94, 1.67 for breast [p trend = 0.33] and HR = 1.18; 95% CI: 0.84, 1.86 for colorectal cancer [p trend = 0.39]). We conclude that a risk factor that increases disease incidence will increase disease-specific mortality. Yet, its influence on postdiagnosis survival can vary, and requires consideration of additional design and analysis issues such as selection bias. Quantitative tools allow joint modeling to compare an exposure's influence on time from enrollment to disease incidence and time from diagnosis to death. © 2017 UICC.

  14. Orthotopic Patient-Derived Glioblastoma Xenografts in Mice.

    Science.gov (United States)

    Xu, Zhongye; Kader, Michael; Sen, Rajeev; Placantonakis, Dimitris G

    2018-01-01

    Patient-derived xenografts (PDX) provide in vivo glioblastoma (GBM) models that recapitulate actual tumors. Orthotopic tumor xenografts within the mouse brain are obtained by injection of GBM stem-like cells derived from fresh surgical specimens. These xenografts reproduce GBM's histologic complexity and hallmark biological behaviors, such as brain invasion, angiogenesis, and resistance to therapy. This method has become essential for analyzing mechanisms of tumorigenesis and testing the therapeutic effect of candidate agents in the preclinical setting. Here, we describe a protocol for establishing orthotopic tumor xenografts in the mouse brain with human GBM cells.

  15. Beyond KRAS mutation status: influence of KRAS copy number status and microRNAs on clinical outcome to cetuximab in metastatic colorectal cancer patients

    Directory of Open Access Journals (Sweden)

    Mekenkamp Leonie JM

    2012-07-01

    Full Text Available Abstract Background KRAS mutation is a negative predictive factor for treatment with anti-epidermal growth factor receptor (EGFR antibodies in metastatic colorectal cancer (mCRC. Novel predictive markers are required to further improve the selection of patients for this treatment. We assessed the influence of modification of KRAS by gene copy number aberration (CNA and microRNAs (miRNAs in correlation to clinical outcome in mCRC patients treated with cetuximab in combination with chemotherapy and bevacizumab. Methods Formalin-fixed paraffin-embedded primary tumour tissue was used from 34 mCRC patients in a phase III trial, who were selected based upon their good (n = 17 or poor (n = 17 progression-free survival (PFS upon treatment with cetuximab in combination with capecitabine, oxaliplatin, and bevacizumab. Gene copy number at the KRAS locus was assessed using high resolution genome-wide array CGH and the expression levels of 17 miRNAs targeting KRAS were determined by real-time PCR. Results Copy number loss of the KRAS locus was observed in the tumour of 5 patients who were all good responders including patients with a KRAS mutation. Copy number gains in two wild-type KRAS tumours were associated with a poor PFS. In KRAS mutated tumours increased miR-200b and decreased miR-143 expression were associated with a good PFS. In wild-type KRAS patients, miRNA expression did not correlate with PFS in a multivariate model. Conclusions Our results indicate that the assessment of KRAS CNA and miRNAs targeting KRAS might further optimize the selection of mCRC eligible for anti-EGFR therapy.

  16. The influence of high-intensity compared with moderate-intensity exercise training on cardiorespiratory fitness and body composition in colorectal cancer survivors: a randomised controlled trial.

    Science.gov (United States)

    Devin, James L; Sax, Andrew T; Hughes, Gareth I; Jenkins, David G; Aitken, Joanne F; Chambers, Suzanne K; Dunn, Jeffrey C; Bolam, Kate A; Skinner, Tina L

    2016-06-01

    Following colorectal cancer diagnosis and anti-cancer therapy, declines in cardiorespiratory fitness and body composition lead to significant increases in morbidity and mortality. There is increasing interest within the field of exercise oncology surrounding potential strategies to remediate these adverse outcomes. This study compared 4 weeks of moderate-intensity exercise (MIE) and high-intensity exercise (HIE) training on peak oxygen consumption (V̇O2peak) and body composition in colorectal cancer survivors. Forty seven post-treatment colorectal cancer survivors (HIE = 27 months post-treatment; MIE = 38 months post-treatment) were randomised to either HIE [85-95 % peak heart rate (HRpeak)] or MIE (70 % HRpeak) in equivalence with current physical activity guidelines and completed 12 training sessions over 4 weeks. HIE was superior to MIE in improving absolute (p = 0.016) and relative (p = 0.021) V̇O2peak. Absolute (+0.28 L.min(-1), p body composition for colorectal cancer survivors. HIE appears to offer superior improvements in cardiorespiratory fitness and body composition in comparison to current physical activity recommendations for colorectal cancer survivors and therefore may be an effective clinical utility following treatment.

  17. The research on the influences of hyperthermal perfusion chemotherapy combined with immunologic therapy on the immunologic function and levels of circulating tumor cells of the advanced colorectal cancer patients with liver metastasis.

    Science.gov (United States)

    Sun, J-J; Fan, G-L; Wang, X-G; Xu, K

    2017-07-01

    To investigated the influence of hyperthermal perfusion chemotherapy combined with immunologic therapy on the immunologic function and levels of circulating tumor cells of the advanced colorectal cancer patients with liver metastasis. We enrolled 98 advanced colorectal cancer patients with liver metastasis that were admitted to this hospital for treatment and were randomly divided into two groups, the observation group (n = 49) and the control group (n = 49). We administered systemic vein chemotherapy for patients in the control group, and hyperthermal perfusion chemotherapy for the patients in the observation group in order to compare the subgroup levels of T lymphocytes, NK cells and immunoglobulin (IgG, IgA, and IgM) in the immune system of patients in both groups. We also assayed the circulating tumor cells (CTC) in the peripheral blood of patients in both groups using the cell search method, and compared the efficacy using response evaluation criteria in solid tumors and the survival rates of patients in both groups using the Kaplan-Meier method. After two treatment courses, the levels of CD3+, CD4+ and CD4+/CD8+ of the patients in the observation group were significantly higher than those of the control group, but the levels of CD8+ of patients in the observation group was lower than that in the control group (pfunctions of patients for the indirect anti-tumor effect, a significant decrease in CTC of patients, and a higher long-term survival rate have been achieved in the treatment with hyperthermal perfusion chemotherapy combined with immunologic therapy for the advanced colorectal cancer patients with liver metastasis. Thus, it can serve as the preferable drug for the treatment of advanced colorectal cancer with liver metastasis.

  18. HER2 activating mutations are targets for colorectal cancer treatment.

    Science.gov (United States)

    Kavuri, Shyam M; Jain, Naveen; Galimi, Francesco; Cottino, Francesca; Leto, Simonetta M; Migliardi, Giorgia; Searleman, Adam C; Shen, Wei; Monsey, John; Trusolino, Livio; Jacobs, Samuel A; Bertotti, Andrea; Bose, Ron

    2015-08-01

    The Cancer Genome Atlas project identified HER2 somatic mutations and gene amplification in 7% of patients with colorectal cancer. Introduction of the HER2 mutations S310F, L755S, V777L, V842I, and L866M into colon epithelial cells increased signaling pathways and anchorage-independent cell growth, indicating that they are activating mutations. Introduction of these HER2 activating mutations into colorectal cancer cell lines produced resistance to cetuximab and panitumumab by sustaining MAPK phosphorylation. HER2 mutants are potently inhibited by low nanomolar doses of the irreversible tyrosine kinase inhibitors neratinib and afatinib. HER2 gene sequencing of 48 cetuximab-resistant, quadruple (KRAS, NRAS, BRAF, and PIK3CA) wild-type (WT) colorectal cancer patient-derived xenografts (PDX) identified 4 PDXs with HER2 mutations. HER2-targeted therapies were tested on two PDXs. Treatment with a single HER2-targeted drug (trastuzumab, neratinib, or lapatinib) delayed tumor growth, but dual HER2-targeted therapy with trastuzumab plus tyrosine kinase inhibitors produced regression of these HER2-mutated PDXs. HER2 activating mutations cause EGFR antibody resistance in colorectal cell lines, and PDXs with HER2 mutations show durable tumor regression when treated with dual HER2-targeted therapy. These data provide a strong preclinical rationale for clinical trials targeting HER2 activating mutations in metastatic colorectal cancer. ©2015 American Association for Cancer Research.

  19. Dietary patterns and colorectal adenomas in Lynch syndrome: the GEOLynch cohort study

    NARCIS (Netherlands)

    Botma, A.; Vasen, H.F.; Duijnhoven, F.J.B. van; Kleibeuker, J.H.; Nagengast, F.M.; Kampman, E.

    2013-01-01

    BACKGROUND: Patients with Lynch syndrome (LS) have a high risk of developing colorectal cancer due to mutations in mismatch repair genes. Because dietary factors, alone and in combination, influence sporadic colorectal carcinogenesis, the association of dietary patterns with colorectal adenomas in

  20. Dietary Patterns and Colorectal Adenomas in Lynch Syndrome: The GEOLynch Cohort Study

    NARCIS (Netherlands)

    Botma, A.; Vasen, H.F.; Duijnhoven, van F.J.B.; Kleibeuker, J.H.; Nagengast, F.M.; Kampman, E.

    2013-01-01

    BACKGROUND: Patients with Lynch syndrome (LS) have a high risk of developing colorectal cancer due to mutations in mismatch repair genes. Because dietary factors, alone and in combination, influence sporadic colorectal carcinogenesis, the association of dietary patterns with colorectal adenomas in

  1. Dietary Patterns and Colorectal Adenomas in Lynch Syndrome The GEOLynch Cohort Study

    NARCIS (Netherlands)

    Botma, Akke; Vasen, Hans F. A.; van Duijnhoven, Franzel J. B.; Kleibeuker, Jan H.; Nagengast, Fokko M.; Kampman, Ellen

    2013-01-01

    BACKGROUND: Patients with Lynch syndrome (LS) have a high risk of developing colorectal cancer due to mutations in mismatch repair genes. Because dietary factors, alone and in combination, influence sporadic colorectal carcinogenesis, the association of dietary patterns with colorectal adenomas in

  2. Let-7 miRNA-binding site polymorphism in the KRAS 3′UTR; colorectal cancer screening population prevalence and influence on clinical outcome in patients with metastatic colorectal cancer treated with 5-fluorouracil and oxaliplatin +/− cetuximab

    Directory of Open Access Journals (Sweden)

    Kjersem Janne B

    2012-11-01

    Full Text Available Abstract Background Recent studies have reported associations between a variant allele in a let-7 microRNA complementary site (LCS6 within the 3′untranslated region (3′UTR of KRAS (rs61764370 and clinical outcome in metastatic colorectal cancer (mCRC patients receiving cetuximab. The variant allele has also been associated with increased cancer risk. We aimed to reveal the incidence of the variant allele in a colorectal cancer screening population and to investigate the clinical relevance of the variant allele in mCRC patients treated with 1st line Nordic FLOX (bolus 5-fluorouracil/folinic acid and oxaliplatin +/− cetuximab. Methods The feasibility of the variant allele as a risk factor for CRC was investigated by comparing the LCS6 gene frequencies in 197 CRC patients, 1060 individuals with colorectal polyps, and 358 healthy controls. The relationship between clinical outcome and LCS6 genotype was analyzed in 180 mCRC patients receiving Nordic FLOX and 355 patients receiving Nordic FLOX + cetuximab in the NORDIC-VII trial (NCT00145314. Results LCS6 frequencies did not vary between CRC patients (23%, individuals with polyps (20%, and healthy controls (20% (P = 0.50. No statistically significant differences were demonstrated in the NORDIC-VII cohort even if numerically increased progression-free survival (PFS and overall survival (OS were found in patients with the LCS6 variant allele (8.5 (95% CI: 7.3-9.7 months versus 7.8 months (95% CI: 7.4-8.3 months, P = 0.16 and 23.5 (95% CI: 21.6-25.4 months versus 19.5 months (95% CI: 17.8-21.2 months, P = 0.31, respectively. Addition of cetuximab seemed to improve response rate more in variant carriers than in wild-type carriers (from 35% to 57% versus 44% to 47%, however the difference was not statistically significant (interaction P = 0.16. Conclusions The LCS6 variant allele does not seem to be a risk factor for development of colorectal polyps or CRC. No statistically significant effect of the

  3. [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.

  4. Influence of long-term colonoscopic surveillance on incidence of colorectal cancer and death from the disease in patients with precursors (adenomas)

    DEFF Research Database (Denmark)

    Jørgensen, Ole Dan; Kronborg, Ole; Fenger, Claus

    2007-01-01

    Case-control studies and short term prospective studies have suggested that selected groups of patients with precursors of colorectal cancer may benefit from colonoscopic surveillance after initial removal of adenomas. The aim of the present study was to demonstrate such a possible benefit from...... long term (1-24 years) colonoscopic surveillance in a population of patients with all types of adenomas regardless of size and way of removal. Two thousand and forty-one patients with a first time diagnosis of colorectal adenoma were included in prospective surveillance between year 1978 and 2002. All...

  5. Functional and prognostic influence of receptor polymorphisms in the vascular endothelial growth factor system in colorectal cancer

    DEFF Research Database (Denmark)

    Hansen, T; Spindler, K G; Aalund Olsen, Dorte

    2009-01-01

    was significantly higher than the median protein concentration of the CC genotype, p = 0.005. The CC genotype held prognostic information compared to CT and TT genotypes for both SNP's, pinfluence on the VEGFR-2 protein level, and the -604 T/C SNP...... on the gene expression level in CRC patients. The results furthermore indicate a prognostic influence of both SNP's on progression-free survival. No significant financial relationships to disclose.......e15032 Background: The vascular endothelial growth factor (VEGF) system plays a key role in the angiogenic process ensuring a sufficient blood supply to the growth of malignant tumours. The clinical importance of single nucleotide polymorphisms (SNP's) in the VEGF receptors is still unknown...

  6. Influence of caseload and surgical speciality on outcome following surgery for colorectal cancer: a review of evidence. Part 2: long-term outcome

    DEFF Research Database (Denmark)

    Iversen, Lene H.; Harling, H; Laurberg, S

    2007-01-01

    OBJECTIVE: We reviewed recent literature to assess the impact of hospital caseload, surgeon's caseload and education on long-term outcome following colorectal cancer surgery. METHOD: We searched the MEDLINE and Cochrane Library databases for relevant literature starting from 1992. We selected...

  7. Age at diagnosis of inflammatory bowel disease influences early development of colorectal cancer in inflammatory bowel disease patients: A nationwide, long-term survey

    NARCIS (Netherlands)

    J.E. Baars (Judith); E.J. Kuipers (Ernst); M. van Haastert (M.); J.J. Nicolai (Jan); A.C. Poen (Alexander); C.J. van der Woude (Janneke)

    2012-01-01

    textabstractBackground: Data on clinical characteristics of patients with inflammatory bowel disease (IBD)-related colorectal cancer (CRC) are scarce and mainly originate from tertiary referral centres. We studied patient and disease characteristics of IBD-related CRC in a nationwide IBD cohort in

  8. In vivo bioluminescence imaging using orthotopic xenografts towards patient's derived-xenograft Medulloblastoma models.

    Science.gov (United States)

    Asadzadeh, Fatemeh; Ferrucci, Veronica; DE Antonellis, Pasqualino; Zollo, Massimo

    2017-03-01

    Medulloblastoma is a cerebellar neoplasia of the central nervous system. Four molecular subgrups have been identified (MBWNT, MBSHH, MBgroup3 and MBgroup4) with distinct genetics and clinical outcome. Among these, MBgroup3-4 are highly metastatic with the worst prognosis. The current standard therapy includes surgery, radiation and chemotherapy. Thus, specific treatments adapted to cure those different molecular subgroups are needed. The use of orthotopic xenograft models, together with the non-invasive in vivo biolumiscence imaging (BLI) technology, is emerging during preclinical studies to test novel therapeutics for medulloblastoma treatment. Orthotopic MB xenografts were performed by injection of Daoy-luc cells, that had been previously infected with lentiviral particles to stably express luciferase gene, into the fourth right ventricle of the cerebellum of ten nude mice. For the implantation, specific stereotactic coordinates were used. Seven days after the implantation the mice were imaged by acquisitions of bioluminescence imaging (BLI) using IVIS 3D Illumina Imaging System (Xenogen). Tumor growth was evaluated by quantifying the bioluminescence signals using the integrated fluxes of photons within each area of interest using the Living Images Software Package 3.2 (Xenogen-Perkin Elmer). Finally, histological analysis using hematoxylin-eosin staining was performed to confirm the presence of tumorigenic cells into the cerebellum of the mice. We describe a method to use the in vivo bioluminescent imaging (BLI) showing the potential to be used to investigate the potential antitumorigenic effects of a drug for in vivo medulloblastoma treatment. We also discuss other studies in which this technology has been applied to obtain a more comprehensive knowledge of medulloblastoma using orthotopic xenograft mouse models. There is a need to develop patient's derived-xenograft (PDX) model systems to test novel drugs for medulloblastoma treatment within each molecular sub

  9. Colorectal Cancer: A Personal Journey

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Colorectal Cancer Colorectal Cancer: A Personal Journey Past Issues / Summer 2016 Table ... Carmen Marc Valvo is an outspoken voice for colorectal cancer screening. Photo Courtesy of: Phil Fisch Photography Designer ...

  10. Metachronous colorectal carcinoma

    DEFF Research Database (Denmark)

    Bülow, Steffen; Svendsen, L B; Mellemgaard, A

    1990-01-01

    During the period 1943-67, 903 Danish patients aged less than 40 years had colorectal carcinoma. The patients were followed up for up to 41 years and during this period 44 of 501 (9 per cent) operated on for cure developed a metachronous colorectal carcinoma. The cumulative risk of a metachronous...... colorectal carcinoma was 30 per cent after up to 41 years of observation. The occurrence of a metachronous colorectal carcinoma was evenly distributed in the observation period. The cumulative survival rate after operation for a metachronous colorectal carcinoma was 41 per cent after 20 years of observation....... We propose a lifelong follow-up programme after resection of colorectal carcinoma for cure in this age group, including annual Hemoccult test and colonoscopy at 3-year intervals....

  11. The influence of the periodontal biotype on peri-implant tissues around immediate implants with and without xenografts. Clinical and micro-computerized tomographic study in small Beagle dogs.

    Science.gov (United States)

    Maia, Luciana P; Reino, Danilo M; Muglia, Valdir A; de Souza, Sérgio L S; Palioto, Daniela B; Novaes, Arthur B

    2015-01-01

    Soft tissues and buccal bone plate remodeling after immediate implantation in sockets with thin buccal bone, using the flapless approach with or without bone graft into the buccal gap, was compared between sites with thin and normal gingiva. Eight dogs had the gingiva of one side of the mandible thinned, the mandibular premolars were extracted without flaps, and 4 implants were installed in each side, positioned 1.5 mm from the buccal bone. The sites were randomly assigned into: TG (test group) = thin gingiva; TG + GM (TG with grafting material); CG (control group) = normal gingiva; and CG + GM (CG with grafting material). Buccal bone thickness (BBT), thickness of keratinized tissue (TKT), alveolar thickness (AT), gingival recession (GR), and probing depth (PD) were clinically evaluated. Within 12 weeks the dogs were sacrificed and the samples were analyzed by micro-computerized tomography. A thin BBT was observed in all the dogs. The presurgical procedures reduced TKT in the test group, with minimal changes of the AT. There were no statistically significant differences among the groups for the clinical parameters and the tomographic analysis showed similar linear and tri-dimensional bone reduction in all the groups. The thickness of the buccal bone was a fundamental factor in buccal bone plate resorption, even with flapless implantation. The decrease in gingival thickness or the addition of a biomaterial in the gap did not influence the results. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Optimal specific radioactivity of anti-HER2 Affibody molecules enables discrimination between xenografts with high and low HER2 expression levels

    Energy Technology Data Exchange (ETDEWEB)

    Tolmachev, Vladimir [Uppsala University, Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala (Sweden); Uppsala University, Department of Medical Sciences, Nuclear Medicine, Uppsala (Sweden); Waallberg, Helena [Royal Institute of Technology, School of Biotechnology, Stockholm (Sweden); Sandstroem, Mattias [Uppsala University Hospital, Section of Hospital Physics, Department of Oncology, Uppsala (Sweden); Hansson, Monika; Wennborg, Anders [Affibody AB, Stockholm (Sweden); Orlova, Anna [Uppsala University, Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala (Sweden)

    2011-03-15

    Overexpression of the HER2 receptor is a biomarker for predicting those patients who may benefit from trastuzumab therapy. Radiolabelled Affibody molecules can be used to visualize HER2 expression in tumour xenografts with high sensitivity. However, previous studies demonstrated that the difference in uptake in xenografts with high and low HER2 expression levels is not proportional to the difference in expression levels. We hypothesized that discrimination between tumours with high and low HER2 expression may be improved by increasing the injected dose (reducing the specific activity) of the tracer. The influence of injected dose of anti-HER2 {sup 111}In-DOTA-Z{sub HER2} {sub 342} Affibody molecule on uptake in SKOV-3 (high HER2 expression) and LS174T (low expression) xenografts was investigated. The optimal range of injected doses enabling discrimination between xenografts with high and low expression was determined. To verify this, tumour uptake was measured in mice carrying both SKOV-3 and LS174T xenografts after injection of either 1 or 15 {mu}g {sup 111}In-DOTA-Z{sub HER2:342}. An increase in the injected dose caused a linear decrease in the radioactivity accumulation in the LS174T xenografts (low HER2 expression). For SKOV-3 xenografts, the dependence of the tumour uptake on the injected dose was less dramatic. The injection of 10-30 {mu}g {sup 111}In-DOTA-Z{sub HER2:342} per mouse led to the largest difference in uptake between the two types of tumour. Experiments in mice bearing two xenografts confirmed that the optimized injected dose enabled better discrimination of expression levels. Careful optimization of the injected dose of Affibody molecules is required for maximum discrimination between xenografts with high and low levels of HER2 expression. This information has potential relevance for clinical imaging applications. (orig.)

  13. 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

  14. 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, pcolorectal cancer influenced the risk of postoperative colorectal neoplasms. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  15. Immunogenomic Classification of Colorectal Cancer and Therapeutic Implications

    NARCIS (Netherlands)

    Roelands, Jessica; Kuppen, Peter J. K.; Vermeulen, Louis; Maccalli, Cristina; Decock, Julie; Wang, Ena; Marincola, Francesco M.; Bedognetti, Davide; Hendrickx, Wouter

    2017-01-01

    The immune system has a substantial effect on colorectal cancer (CRC) progression. Additionally, the response to immunotherapeutics and conventional treatment options (e.g., chemotherapy, radiotherapy and targeted therapies) is influenced by the immune system. The molecular characterization of

  16. Physicochemical characterization of two deproteinized bovine xenografts

    Directory of Open Access Journals (Sweden)

    Thais Accorsi-Mendonça

    2008-03-01

    Full Text Available Calcium phosphate salts, or more specifically hydroxyapatite, are products of great interest in the fields of medical and dental science due to their biocompatibility and osteoconduction property. Deproteinized xenografts are primarily constituted of natural apatites, sintered or not. Variations in the industrial process may affect physicochemical properties and, therefore, the biological outcome. The purpose of this work was to characterize the physical and chemical properties of deproteinized xenogenic biomaterials, Bio-Oss (Geistlich Biomaterials, Wolhuser, Switzerland and Gen-Ox (Baumer S.A., Brazil, widely used as bone grafts. Scanning electron microscopy, infrared region spectroscopy, X-ray diffraction, thermogravimetry and degradation analysis were conducted. The results show that both materials presented porous granules, composed of crystalline hydroxyapatite without apparent presence of other phases. Bio-Oss presented greater dissolution in Tris-HCl than Gen-Ox in the degradation test, possibly due to the low crystallinity and the presence of organic residues. In conclusion, both commercial materials are hydroxyapatite compounds, Bio-Oss being less crystalline than Gen-Ox and, therefore, more prone to degradation.

  17. Synchronous colorectal liver metastases

    NARCIS (Netherlands)

    A.E.M. van der Pool (Anne)

    2011-01-01

    textabstractColorectal cancer is one of the most common malignancies worldwide and ranks second in cancer-related deaths in many parts of the Western world. Once in the lymph or blood vessels, colorectal cancer can quickly spread and the liver is known to be a favourable site for metastases. The

  18. [Obesity and colorectal cancer].

    Science.gov (United States)

    Na, Soo-Young; Myung, Seung-Jae

    2012-01-01

    Obesity worldwide is constantly increasing. Obesity acts as an independent significant risk factor for malignant tumors of various organs including colorectal cancer. Visceral adipose tissue is physiologically more important than subcutaneous adipose tissue. The relative risk of colorectal cancer of obese patients is about 1.5 times higher than the normal-weight individuals, and obesity is also associated with premalignant colorectal adenoma. The colorectal cancer incidence of obese patients has gender-specific and site-specific characteristics that it is higher in men than women and in the colon than rectum. Obesity acts as a risk factor of colorectal carcinogenesis by several mechanisms. Isulin, insulin-like growth factor, leptin, adiponectin, microbiome, and cytokines of chronic inflammation etc. have been understood as its potential mechanisms. In addition, obesity in patients with colorectal cancer negatively affects the disease progression and response of chemotherapy. Although the evidence is not clear yet, there are some reports that weight loss as well as life-modification such as dietary change and physical activity can reduce the risk of colorectal cancer. It is very important knowledge in the point that obesity is a potentially modifiable risk factor that can alter the incidence and outcome of the colorectal cancer.

  19. Global Conservation of Protein Status between Cell Lines and Xenografts

    Directory of Open Access Journals (Sweden)

    Julian Biau

    2016-08-01

    Full Text Available Common preclinical models for testing anticancer treatment include cultured human tumor cell lines in monolayer, and xenografts derived from these cell lines in immunodeficient mice. Our goal was to determine how similar the xenografts are compared with their original cell line and to determine whether it is possible to predict the stability of a xenograft model beforehand. We studied a selection of 89 protein markers of interest in 14 human cell cultures and respective subcutaneous xenografts using the reverse-phase protein array technology. We specifically focused on proteins and posttranslational modifications involved in DNA repair, PI3K pathway, apoptosis, tyrosine kinase signaling, stress, cell cycle, MAPK/ERK signaling, SAPK/JNK signaling, NFκB signaling, and adhesion/cytoskeleton. Using hierarchical clustering, most cell culture-xenograft pairs cluster together, suggesting a global conservation of protein signature. Particularly, Akt, NFkB, EGFR, and Vimentin showed very stable protein expression and phosphorylation levels highlighting that 4 of 10 pathways were highly correlated whatever the model. Other proteins were heterogeneously conserved depending on the cell line. Finally, cell line models with low Akt pathway activation and low levels of Vimentin gave rise to more reliable xenograft models. These results may be useful for the extrapolation of cell culture experiments to in vivo models in novel targeted drug discovery.

  20. Physicochemical characterization of porcine bone-derived grafting material and comparison with bovine xenografts for dental applications.

    Science.gov (United States)

    Lee, Jung Heon; Yi, Gyu Sung; Lee, Jin Woong; Kim, Deug Joong

    2017-12-01

    The physicochemical properties of a xenograft are very important because they strongly influence the bone regeneration capabilities of the graft material. Even though porcine xenografts have many advantages, only a few porcine xenografts are commercially available, and most of their physicochemical characteristics have yet to be reported. Thus, in this work we aimed to investigate the physicochemical characteristics of a porcine bone grafting material and compare them with those of 2 commercially available bovine xenografts to assess the potential of xenogenic porcine bone graft materials for dental applications. We used various characterization techniques, such as scanning electron microscopy, the Brunauer-Emmett-Teller adsorption method, atomic force microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, and others, to compare the physicochemical properties of xenografts of different origins. The porcine bone grafting material had relatively high porosity (78.4%) and a large average specific surface area (SSA; 69.9 m 2 /g), with high surface roughness (10-point average roughness, 4.47 µm) and sub-100-nm hydroxyapatite crystals on the surface. Moreover, this material presented a significant fraction of sub-100-nm pores, with negligible amounts of residual organic substances. Apart from some minor differences, the overall characteristics of the porcine bone grafting material were very similar to those of one of the bovine bone grafting material. However, many of these morphostructural properties were significantly different from the other bovine bone grafting material, which exhibited relatively smooth surface morphology with a porosity of 62.0% and an average SSA of 0.5 m 2 /g. Considering that both bovine bone grafting materials have been successfully used in oral surgery applications in the last few decades, this work shows that the porcine-derived grafting material possesses most of the key physiochemical characteristics required for its

  1. MicroRNA-103 Promotes Colorectal Cancer by Targeting Tumor Suppressor DICER and PTEN

    Directory of Open Access Journals (Sweden)

    Li Geng

    2014-05-01

    Full Text Available MicroRNAs (miRNAs are a class of small, noncoding RNAs that act as key regulators in various physiological and pathological processes. However, the regulatory mechanisms for miRNAs in colorectal cancer remain largely unknown. Here, we found that miR-103 is up-regulated in colorectal cancer and its overexpression is closely associated with tumor proliferation and migration. In addition, repressing the expression of miR-103 apparently inhibits colorectal cancer cell proliferation and migration in vitro and HCT-116 xenograft tumor growth in vivo. Subsequent software analysis and dual-luciferase reporter assay identified two tumor suppressor genes DICER and PTEN as direct targets of miR-103, and up-regulation of DICER and PTEN obtained similar results to that occurred in the silencing of miR-103. In addition, restoration of DICER and PTEN can inhibit miR-103-induced colorectal cancer cell proliferation and migration. Our data collectively demonstrate that miR-103 is an oncogene miRNA that promotes colorectal cancer proliferation and migration through down-regulation of the tumor suppressor genes DICER and PTEN. Thus, miR-103 may represent a new potential diagnostic and therapeutic target for colorectal cancer treatment.

  2. Detection of colorectal neoplasia

    DEFF Research Database (Denmark)

    Wilhelmsen, Michael; Christensen, Ib J; Rasmussen, Louise

    2017-01-01

    Serological biomarkers may be an option for early detection of colorectal cancer (CRC). The present study assessed eight cancer-associated protein biomarkers in plasma from subjects undergoing first time ever colonoscopy due to symptoms attributable to colorectal neoplasia. Plasma AFP, CA19-9, CEA...... value was 18% and the negative predictive value was 97%. Combinations of serological protein biomarkers provided a significant identification of subjects with high risk of the presence of colorectal neoplasia. The present set of biomarkers could become important adjunct in early detection of CRC....

  3. 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...... 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...... procedures for colorectal cancer. Therefore, results of present research, validating RAE tests, are awaited with interest....

  4. The influence of preoperative nutritional status on the outcomes of an enhanced recovery after surgery (ERAS) programme for colorectal cancer surgery.

    Science.gov (United States)

    Lohsiriwat, V

    2014-11-01

    The aim of the present study was to evaluate the effects of preoperative nutritional status on the short-term outcomes of an enhanced recovery after surgery (ERAS) programme for colorectal cancer surgery. This prospective observational study included 149 patients who underwent elective resection of colorectal cancer with ERAS from January 2011 to January 2014 in a university hospital. Subjective global assessment (SGA) was used to determine preoperative nutritional status. Primary outcomes included the length of postoperative stay, postoperative morbidity, gastrointestinal recovery, and 30-day readmission. The patients were divided into 3 groups according to the SGA classification. There were 96 patients (64.4 %) in SGA-A (well-nourished), 48 (32.2 %) in SGA-B (mild to moderately malnourished), and 5 (3.4 %) in SGA-C (severely malnourished). Patients in SGA-A had the median length of postoperative stay of 4 days (range 2-23), which was significantly shorter compared to SGA-B (5 days; range 2-16; p recovery of gastrointestinal function, and prolonged length of hospital stay.

  5. Natural killer cells inhibit oxaliplatin-resistant colorectal cancer by repressing WBSCR22 via upregulating microRNA-146b-5p.

    Science.gov (United States)

    Zhao, Haiyan; Su, Wuyun; Kang, Qingmei; Xing, Ze; Lin, Xue; Wu, Zhongjun

    2018-01-01

    Natural killer (NK) cells have exhibited promising efficacy in inhibiting cancer growth. We aimed to explorer the effect of NK cells on oxaliplatin-resistant colorectal cancer and the underlying molecular mechanism. Oxaliplatin-resistant colorectal cancer cell lines were co-cultured with NK cells to evaluate the effect on viability, proliferation, migration and invasion in vitro . Oxaliplatin-resistant colorectal cancer cells were also co-injected with NK cells into mice to establish xenograft tumor model, to assess the in vivo effect of NK cells on tumorigenesis of the oxaliplatin-resistant colorectal cancer cells. Expression of WBSCR22 gene was assessed in the oxaliplatin-resistant colorectal cancer cells following NK cell treatment to elucidate the mechanism. NK cell treatment significantly reduces growth of oxaliplatin-resistant colorectal cancer cells both in vitro and in vivo , as well as reduced WBSCR22 expression. MicroRNAs potentially targeting WBSCR22 were analyzed, and microRNA-146b-5p was found to be significantly upregulated following NK cell treatment. MicroRNA-146b-5p directly targeted WBSCR22 mRNA 3'-UTR to inhibit its expression, which was required for NK cell-induced inhibition of oxaliplatin-resistant colorectal cancer cell lines. NK cells inhibit oxaliplatin-resistant colorectal cancer by repressing WBSCR22 via upregulating microRNA-146b-5p, both of which could serve as candidates for targeted therapy against oxaliplatin-resistant colorectal cancer.

  6. 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...

  7. 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...... 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........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...

  8. 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....

  9. Perceptions of Malaysian colorectal cancer patients regarding dietary intake: a qualitative exploration.

    Science.gov (United States)

    Yusof, Afzaninawati Suria; Isa, Zaleha Md; Shah, Shamsul Azhar

    2013-01-01

    Changes in dietary practices are known to be associated with changes in the health and disease pattern of a population. This study aimed to qualitatively explore the perception of colorectal cancer patients regarding causes of colorectal cancer and the influence of diet. Twelve respondents from three major ethnicities in Malaysia were selected from the quantitative study on dietary pattern and colorectal cancer carried out earlier in this study. In-depth interviews (IDI), conducted from April until June 2012, were mainly in the Malay language with additional use of English and continued until the saturation point was reached. All interviews were autorecorded so that verbatim transcriptions could be created. Causes of colorectal cancer were categorized into internal and external factors. The majority of respondents agreed that there is an association between Western foods and colorectal cancer. Malaysian traditional diet was not related to colorectal cancer as less preservative agents were used. Malaysian diet preparation consisting of taste of cooking (spicy, salty and sour foods) plus type of cooking (fry, grilled and smoked) were considered causes of colorectal cancer. All respondents changed their dietary pattern to healthy food after being diagnosed with colorectal cancer. Advice from doctors regarding suitable food for colorectal cancer was useful in this regard. Eating outside, use of food flavoring ingredients and preservative agents were considered to be the main factors causing colorectal cancer. All respondents admitted that they changed to a healthy diet after being diagnosed with colorectal cancer.

  10. Colorectal cancer screening

    OpenAIRE

    Plumb, A. A.; Halligan, S.

    2015-01-01

    Colorectal cancer is a major public health burden worldwide. There is clear-cut evidence that screening will reduce colorectal cancer mortality and the only contentious issue is which screening tool to use. Most evidence points towards screening with fecal occult blood testing. The immunochemical fecal occult blood tests have a higher sensitivity than the guaiac-based tests. In addition, their automation and haemoglobin quantification allows a threshold for colonoscopy to be selected that can...

  11. Screening for colorectal cancer.

    Science.gov (United States)

    He, Jin; Efron, Jonathan E

    2011-01-01

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

  12. Allografts versus Equine Xenografts in Calcaneal Fracture Repair.

    Science.gov (United States)

    Sonmez, Mehmet Mesut; Armagan, Raffi; Ugurlar, Meric; Eren, Tugrul

    Displaced intra-articular calcaneal fractures are difficult to treat. We determined the functional results and complications of using allografts or equine xenografts in treating these fractures. We reviewed patients seen at our center from May 2011 to December 2014 with Sanders type III or IV unilateral calcaneal fractures treated with locking plates and an additional bone allograft or equine xenograft. A minimum of 1 year after surgery, a history of infection and functional outcomes were assessed using the American Orthopaedic Foot and Ankle Society clinical rating system. Changes in the Gissane angle (GA) and Böhler angle were assessed from radiographs. Of the 91 eligible patients, 15 were lost to follow-up, leaving a sample of 76 patients (42 males): 45 received allografts (19 for type III and 26 for type IV fractures) and 31 received xenografts (20 for type III and 11 for type IV fractures). The mean age was about 40 years in both groups. After ≥1 year of follow-up, the proportion of patients in the American Orthopaedic Foot and Ankle Society scoring categories did not differ significantly between the 2 groups (mean ankle score, 86.5 in the allograft group and 85.1 in the xenograft group), and the American Orthopaedic Foot and Ankle Society functional outcomes were good or excellent in 69% and 68%, respectively (p = .986). The groups did not differ in the incidence of superficial or deep infection (p = 1.000). The Böhler angles were significantly decreased in the xenograft group. Xenografts might be preferred for repairing intra-articular calcaneal fractures because they can perform as well as allografts, avoid donor site morbidities, and are more available and less expensive than allografts. Copyright © 2017 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  13. Performance of the colorectal cancer screening marker Sept9 is influenced by age, diabetes and arthritis: a nested case-control study

    DEFF Research Database (Denmark)

    Ørntoft, Mai-Britt Worm; Nielsen, Hans Jørgen; Ørntoft, Torben Falck

    2015-01-01

    Background Annually, colorectal cancer (CRC) is diagnosed in >1.4 million subjects worldwide and incidence is increasing. Much effort has therefore been focused on screening, which has proven to reduce cancer-related mortality. The Sept9 DNA-methylation assay is among the most well studied blood......-based screening markers. However, earlier reported performances may be misleading: the Sept9 test was recently examined in two screening based cohorts and yielded performances lower than expected. We hypothesize that comorbidities and/or demographic characteristics affect the results of the Sept9 test. Methods...... Using a retrospective nested case–control study design, we studied plasma from 150 cancer and 150 controls selected from a well-characterized cohort of 4698 subjects referred for diagnostic colonoscopy due to CRC-related symptoms. The cases and controls were matched on age and gender, and moreover cases...

  14. A randomized controlled trial to investigate the influence of low dose radiotherapy on immune stimulatory effects in liver metastases of colorectal cancer

    International Nuclear Information System (INIS)

    Reissfelder, Christoph; Büchler, Markus W; Beckhove, Philipp; Huber, Peter E; Weitz, Jürgen; Timke, Carmen; Schmitz-Winnenthal, Hubertus; Rahbari, Nuh N; Koch, Moritz; Klug, Felix; Roeder, Falk; Edler, Lutz; Debus, Jürgen

    2011-01-01

    Insufficient migration and activation of tumor specific effector T cells in the tumor is one of the main reasons for inadequate host anti-tumor immune response. External radiation seems to induce inflammation and activate the immune response. This phase I/II clinical trial aims to evaluate whether low dose single fraction radiotherapy can improve T cell associated antitumor immune response in patients with colorectal liver metastases. This is an investigator-initiated, prospective randomised, 4-armed, controlled Phase I/II trial. Patients undergoing elective hepatic resection due to colorectal cancer liver metastasis will be enrolled in the study. Patients will receive 0 Gy, 0.5 Gy, 2 Gy or 5 Gy radiation targeted to their liver metastasis. Radiation will be applied by external beam radiotherapy using a 6 MV linear accelerator (Linac) with intensity modulated radiotherapy (IMRT) technique two days prior to surgical resection. All patients admitted to the Department of General-, Visceral-, and Transplantion Surgery, University of Heidelberg for elective hepatic resection are consecutively screened for eligibility into this trial, and written informed consent is obtained before inclusion. The primary objective is to assess the effect of active local external beam radiation dose on, tumor infiltrating T cells as a surrogate parameter for antitumor activity. Secondary objectives include radiogenic treatment toxicity, postoperative morbidity and mortality, local tumor control and recurrence patterns, survival and quality of life. Furthermore, frequencies of systemic tumor reactive T cells in blood and bone marrow will be correlated with clinical outcome. This is a randomized controlled patient blinded trial to assess the safety and efficiency of low dose radiotherapy on metastasis infiltrating T cells and thus potentially enhance the antitumor immune response. ClinicalTrials.gov: http://www.clinicaltrials.gov/ct2/show/NCT01191632

  15. Radioimmunodetection of human tumor xenografts by monoclonal antibody F(ab')/sub 2/ fragments

    Energy Technology Data Exchange (ETDEWEB)

    Herlyn, D.; Munz, D.L.; Herlyn, M.; Koprowski, H.; Powe, J.; Alavi, A.; Meinken, G.E.; Srivastava, S.C.

    1986-01-01

    Procedures are described for the radiolocalization of human tumors by murine monoclonal antibodies (MAb) in animal model systems. Visualization of tumor xenografts was clearer in nude mice compared to experimentally immunosuppressed mice due to the higher tumor viability. MAb localization in tumor tissue was greatly enhanced when F(ab')/sub 2/ fragments rather than intact antibody molecules were used. Although tumors could be visualized with /sup 131/I-, /sup 123/I-or /sup 111/In-labeled MAb fragments without background subtraction, tumor-to-background ratios of radioactivity were highest for /sup 131/I-labeled fragments. /sup 131/I-labeled F(ab')/sub 2/ fragments of eight MAb against human colorectal carcinoma, melanoma or lung carcinoma localized specifically only in those tumors that bound the MAb in vitro and not in unrelated tumors. Radiolabeled fragments of MAb with other specificities (anti-hepatitis virus MAb) did not localize in tumors. All MAb that inhibited tumor growth in nude mice effectively localized these tumors by ..gamma..-scintigraphy. Some MAb were effective in localizing tumors but ineffective in inhibiting their growth. The ability of the specific radiolabeled F(ab')/sub 2/ fragments to localize in tumor grafts correlated significantly with MAb binding affinity and density of antigenic sites on tumor cells together, but not with either in vitro binding parameter alone.

  16. Integrated genomics of ovarian xenograft tumor progression and chemotherapy response

    International Nuclear Information System (INIS)

    Stuckey, Ashley; Brodsky, Alexander S; Fischer, Andrew; Miller, Daniel H; Hillenmeyer, Sara; Kim, Kyu K; Ritz, Anna; Singh, Rakesh K; Raphael, Benjamin J; Brard, Laurent

    2011-01-01

    Ovarian cancer is the most deadly gynecological cancer with a very poor prognosis. Xenograft mouse models have proven to be one very useful tool in testing candidate therapeutic agents and gene function in vivo. In this study we identify genes and gene networks important for the efficacy of a pre-clinical anti-tumor therapeutic, MT19c. In order to understand how ovarian xenograft tumors may be growing and responding to anti-tumor therapeutics, we used genome-wide mRNA expression and DNA copy number measurements to identify key genes and pathways that may be critical for SKOV-3 xenograft tumor progression. We compared SKOV-3 xenografts treated with the ergocalciferol derived, MT19c, to untreated tumors collected at multiple time points. Cell viability assays were used to test the function of the PPARγ agonist, Rosiglitazone, on SKOV-3 cell growth. These data indicate that a number of known survival and growth pathways including Notch signaling and general apoptosis factors are differentially expressed in treated vs. untreated xenografts. As tumors grow, cell cycle and DNA replication genes show increased expression, consistent with faster growth. The steroid nuclear receptor, PPARγ, was significantly up-regulated in MT19c treated xenografts. Surprisingly, stimulation of PPARγ with Rosiglitazone reduced the efficacy of MT19c and cisplatin suggesting that PPARγ is regulating a survival pathway in SKOV-3 cells. To identify which genes may be important for tumor growth and treatment response, we observed that MT19c down-regulates some high copy number genes and stimulates expression of some low copy number genes suggesting that these genes are particularly important for SKOV-3 xenograft growth and survival. We have characterized the time dependent responses of ovarian xenograft tumors to the vitamin D analog, MT19c. Our results suggest that PPARγ promotes survival for some ovarian tumor cells. We propose that a combination of regulated expression and copy number

  17. 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 ( ...

  18. Colorectal Cancer Risk Assessment Tool

    Science.gov (United States)

    ... 11/12/2014 Risk Calculator About the Tool Colorectal Cancer Risk Factors Download SAS and Gauss Code Page ... Rectal Cancer: Prevention, Genetics, Causes Tests to Detect Colorectal Cancer and Polyps Cancer Risk Prediction Resources Update November ...

  19. Comparison of colorectal and gastric cancer: Survival and prognostic factors

    International Nuclear Information System (INIS)

    Moghimi-Dehkordi, Bijan; Safaee, Azadeh; Zali, Mohammad R

    2009-01-01

    Gastric and colorectal cancers are the most common gastrointestinal malignancies in Iran. We aim to compare the survival rates and prognostic factors between these two cancers. We studied 1873 patients with either gastric or colorectal cancer who were registered in one referral cancer registry center in Tehran, Iran. All patients were followed from their time of diagnosis until December 2006 (as failure time). Survival curves were calculated according to the Kaplan-Meier Method and compared by the Log-rank test. Multivariate analysis of prognostic factors was carried out using the Cox proportional hazard model. Of 1873 patients, there were 746 with gastric cancer and 1138 with colorectal cancer. According to the Kaplan-Meier method 1, 3, 5, and 7-year survival rates were 71.2, 37.8, 25.3, and 19.5%, respectively, in gastric cancer patients and 91.1, 73.1, 61, and 54.9%, respectively, in patients with colorectal cancer. Also, univariate analysis showed that age at diagnosis, sex, grade of tumor, and distant metastasis were of prognostic significance in both cancers ( P < 0.0001). However, in multivariate analysis, only distant metastasis in colorectal cancer and age at diagnosis, grade of tumor, and distant metastasis in colorectal cancer were identified as independent prognostic factors influencing survival. According to our findings, survival is significantly related to histological differentiation of tumor and distant metastasis in colorectal cancer patients and only to distant metastasis in gastric cancer patients. (author)

  20. Global phosphotyrosine proteomics identifies PKCδ as a marker of responsiveness to Src inhibition in colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Eliot T McKinley

    Full Text Available Sensitive and specific biomarkers of protein kinase inhibition can be leveraged to accelerate drug development studies in oncology by associating early molecular responses with target inhibition. In this study, we utilized unbiased shotgun phosphotyrosine (pY proteomics to discover novel biomarkers of response to dasatinib, a small molecule Src-selective inhibitor, in preclinical models of colorectal cancer (CRC. We performed unbiased mass spectrometry shotgun pY proteomics to reveal the pY proteome of cultured HCT-116 colonic carcinoma cells, and then extended this analysis to HCT-116 xenograft tumors to identify pY biomarkers of dasatinib-responsiveness in vivo. Major dasatinib-responsive pY sites in xenograft tumors included sites on delta-type protein kinase C (PKCδ, CUB-domain-containing protein 1 (CDCP1, Type-II SH2-domain-containing inositol 5-phosphatase (SHIP2, and receptor protein-tyrosine phosphatase alpha (RPTPα. The pY313 site PKCδ was further supported as a relevant biomarker of dasatinib-mediated Src inhibition in HCT-116 xenografts by immunohistochemistry and immunoblotting with a phosphospecific antibody. Reduction of PKCδ pY313 was further correlated with dasatinib-mediated inhibition of Src and diminished growth as spheroids of a panel of human CRC cell lines. These studies reveal PKCδ pY313 as a promising readout of Src inhibition in CRC and potentially other solid tumors and may reflect responsiveness to dasatinib in a subset of colorectal cancers.

  1. Developments in Colorectal Cancer Screening

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Colorectal Cancer Developments in Colorectal Cancer Screening Past Issues / Summer 2016 Table of ... at the National Cancer Institute, shared developments in colorectal cancer screening methods with NIH MedlinePlus magazine. What ...

  2. Improving Quality in Colorectal Surgery

    NARCIS (Netherlands)

    J.C. Slieker (Juliette)

    2014-01-01

    markdownabstract__Abstract__ Colorectal surgery is an important aspect of our current health system, due to the high incidence of colorectal cancer combined with an ageing population, improved long-term outcomes after colorectal surgery, and the perfectioning of the operative and postoperative

  3. Radiosensitivity of drug-resistant human tumour xenografts

    International Nuclear Information System (INIS)

    Mattern, J.; Bak, M. Jr.; Volm, M.; Hoever, K.H.

    1989-01-01

    The radiosensitivity of three drug-resistant sublines of a human epidermoid lung carcinoma growing as xenografts in nude mice was investigated. Drug resistance to vincristine, actinomycin D and cisplatin was developed in vivo by repeated drug treatment. It was found that all three drug-resistant tumour lines were not cross-resistant to irradiation. (orig.) [de

  4. Exosomal secretion of cytoplasmic prostate cancer xenograft-derived proteins

    NARCIS (Netherlands)

    F.H. Jansen (Flip); J. Krijgsveld (Jeroen); A.L. Rijswijk (Angelique); G.J.C.M. van den Bemd (Gert-Jan); M.S. van den Berg (Mirella); W.M. van Weerden (Wytske); R. Willemsen (Rob); L.J.M. Dekker (Lennard); T.M. Luider (Theo); G.W. Jenster (Guido)

    2009-01-01

    textabstractNovel markers for prostate cancer (PCa) are needed because current established markers such as prostate-specific antigen lack diagnostic specificity and prognostic value. Proteomics analysis of serum from mice grafted with human PCa xenografts resulted in the identification of 44

  5. Next-generation sequence analysis of cancer xenograft models.

    Directory of Open Access Journals (Sweden)

    Fernando J Rossello

    Full Text Available Next-generation sequencing (NGS studies in cancer are limited by the amount, quality and purity of tissue samples. In this situation, primary xenografts have proven useful preclinical models. However, the presence of mouse-derived stromal cells represents a technical challenge to their use in NGS studies. We examined this problem in an established primary xenograft model of small cell lung cancer (SCLC, a malignancy often diagnosed from small biopsy or needle aspirate samples. Using an in silico strategy that assign reads according to species-of-origin, we prospectively compared NGS data from primary xenograft models with matched cell lines and with published datasets. We show here that low-coverage whole-genome analysis demonstrated remarkable concordance between published genome data and internal controls, despite the presence of mouse genomic DNA. Exome capture sequencing revealed that this enrichment procedure was highly species-specific, with less than 4% of reads aligning to the mouse genome. Human-specific expression profiling with RNA-Seq replicated array-based gene expression experiments, whereas mouse-specific transcript profiles correlated with published datasets from human cancer stroma. We conclude that primary xenografts represent a useful platform for complex NGS analysis in cancer research for tumours with limited sample resources, or those with prominent stromal cell populations.

  6. 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 w......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....

  7. Nutritional status assessment in colorectal cancer patients.

    Science.gov (United States)

    Lopes, Joana Pedro; de Castro Cardoso Pereira, Paula Manuela; dos Reis Baltazar Vicente, Ana Filipa; Bernardo, Alexandra; de Mesquita, María Fernanda

    2013-01-01

    The present study intended to evaluate the nutritional status of Portuguese colorectal patients and associated it with surgery type as well as quality of life outcomes. Malnutrition can affect up to 85% of cancer patients and specifically 30-60% in colorectal cancer and can significantly influence health outcomes. A sample of 50 colorectal cancer patients was evaluated in what refers to several anthropometric measures, food intake, clinical history, complications rate before and after surgery procedure. The sample was divided between convention and fast-track procedures. Most of the individuals were overweight or obese but had lost weight on the past six months. Despite mild, there were signs of malnutrition in this sample with high losses of fat free mass, weight and also fat mass during the hospitalization period. These results reinforce the importance of malnutrition assessment in colorectal patients as well as consider weight loss on the past months and body composition in order to complement nutritional status evaluation. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

  8. 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.

  9. 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.

  10. Histological and molecular evaluation of patient-derived colorectal cancer explants.

    Directory of Open Access Journals (Sweden)

    Joshua M Uronis

    Full Text Available Mouse models have been developed to investigate colorectal cancer etiology and evaluate new anti-cancer therapies. While genetically engineered and carcinogen-induced mouse models have provided important information with regard to the mechanisms underlying the oncogenic process, tumor xenograft models remain the standard for the evaluation of new chemotherapy and targeted drug treatments for clinical use. However, it remains unclear to what extent explanted colorectal tumor tissues retain inherent pathological features over time. In this study, we have generated a panel of 27 patient-derived colorectal cancer explants (PDCCEs by direct transplantation of human colorectal cancer tissues into NOD-SCID mice. Using this panel, we performed a comparison of histology, gene expression and mutation status between PDCCEs and the original human tissues from which they were derived. Our findings demonstrate that PDCCEs maintain key histological features, basic gene expression patterns and KRAS/BRAF mutation status through multiple passages. Altogether, these findings suggest that PDCCEs maintain similarity to the patient tumor from which they are derived and may have the potential to serve as a reliable preclinical model that can be incorporated into future strategies to optimize individual therapy for patients with colorectal cancer.

  11. 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.

  12. Association between Fusobacterium nucleatum and colorectal cancer: Progress and future directions

    Science.gov (United States)

    Zhang, Sheng; Cai, Sanjun; Ma, Yanlei

    2018-01-01

    The initiation and progression of colorectal cancer (CRC) involves genetic and epigenetic alterations influenced by dietary and environmental factors. Increasing evidence has linked the intestinal microbiota and colorectal cancer. More recently, Fusobacterium nucleatum (Fn), an opportunistic commensal anaerobe in the oral cavity, has been associated with CRC. Several research teams have reported an overabundance of Fn in human CRC and have elucidated the possible mechanisms by which Fn is involved in colorectal carcinogenesis in vitro and in mouse models. However, the mechanisms by which Fn promotes colorectal carcinogenesis remain unclear. To provide new perspectives for early diagnosis, the identification of high risk populations and treatment for colorectal cancer, this review will summarize the relative research progresses regarding the relationship between Fn and colorectal cancer. PMID:29760804

  13. Radioimmunoguided surgery using the monoclonal antibody B72.3 in colorectal tumors

    International Nuclear Information System (INIS)

    Sickle-Santanello, B.J.; O'Dwyer, P.J.; Mojzisik, C.

    1987-01-01

    The authors have developed a hand-held gamma-detecting probe (GDP) for intraoperative use that improves the sensitivity of external radioimmunodetection. Radiolabeled monoclonal antibody (MAb) B72.3 was injected in six patients with primary colorectal cancer and 31 patients with recurrent colorectal cancer an average of 16 days preoperatively. The GDP localized the MAb B72.3 in 83 percent of sites. The technique, known as a radioimmunoguided surgery (RIGS) system did not alter the surgical procedure in patients with primary colorectal cancer but did alter the approach in 26 percent (8/31) of patients with recurrent colorectal cancer. Two patients avoided unnecessary liver resections and two underwent extraabdominal approaches to document their disease. The RIGS system may influence the short-term morbidity and mortality of surgery for colorectal cancer. Larger series and longer follow-up are needed to determine whether the RIGS system confers a survival advantage to the patient with colorectal cancer

  14. Colorectal cancer screening

    OpenAIRE

    McLoughlin, Monica Ramona

    2008-01-01

    Colorectal cancer is a major public health burden and is the most common cause of mortality from cancer in Europe. Over the last two decades robust evidence from randomised clinical trials and case-control series have confirmed that the mortality from colorectal cancer can be reduced by screening. The challenge over the next decade is how to implement this in clinical practice. This is what we set out to answer with this thesis. Not all individuals are equal when it comes to screening and tho...

  15. A rare variant P507L in TPP1 interrupts TPP1-TIN2 interaction, influences telomere length, and confers colorectal cancer risk in Chinese population.

    Science.gov (United States)

    Li, Jiaoyuan; Chang, Jiang; Tian, Jianbo; Ke, Juntao; Zhu, Ying; Yang, Yang; Gong, Yajie; Zou, Danyi; Peng, Xiating; Yang, Nan; Mei, Shufang; Wang, Xiaoyang; Cheng, Liming; Hu, Weiguo; Gong, Jing; Zhong, Rong; Miao, Xiaoping

    2018-06-11

    Telomere dysfunction triggers cellular senescence and constitutes a driving force for cancer initiation. Genetic variants in genes involved in telomere maintenance may contribute to colorectal cancer (CRC) susceptibility. In this study, we firstly captured germline mutations in 192 CRC patients by sequencing the coding regions of 13 core components implicated in telomere biology. Five potential functional variants were then genotyped and assessed in a case-control set with 3,761 CRC cases and 3,839 healthy controls. The promising association was replicated in additional 6,765 cases and 6,906 controls. Functional experiments were used to further clarify the potential function of the significant variant and uncover the underlying mechanism in CRC development. The two-stage association studies showed that a rare missense variant rs149418249 (c.C1520T, p.P507L) in the 11th exon of TPP1 (also known as ACD, gene ID 65057) was significantly associated with CRC risk with the ORs being 2.90 (95% CI:1.04-8.07, P=0.041), 2.50 (95% CI:1.04-6.04, P=0.042), and 2.66 (95%CI:1.36-5.18, P=0.004) in discovery, replication, and the combined samples, respectively. Further functional annotation indicated that the TPP1 P507L substitution interrupted TPP1-TIN2 interaction, impaired telomerase processivity, and shortened telomere length, which subsequently facilitated cell proliferation and promoted CRC development. A rare variant P507L in TPP1 confers increased risk of CRC through interrupting TPP1-TIN2 interaction, impairing telomerase processivity, and shrinking telomere length. These findings emphasize the important role of telomere dysfunction in CRC development, and provide new insights about the prevention of this type of cancer. Copyright ©2018, American Association for Cancer Research.

  16. Influence of smoking, body mass index and other factors on the preventive effect of nonsteroidal anti-inflammatory drugs on colorectal cancer risk.

    Science.gov (United States)

    Wang, Xiaoliang; Chan, Andrew T; Slattery, Martha L; Chang-Claude, Jenny; Potter, John D; Gallinger, Steven; Caan, Bette; Lampe, Johanna W; Newcomb, Polly A; Zubair, Niha; Hsu, Li; Schoen, Robert E; Hoffmeister, Michael; Brenner, Hermann; Le Marchand, Loic; Peters, Ulrike; White, Emily

    2018-06-19

    Nonsteroidal anti-inflammatory drugs (NSAIDs) use has consistently been associated with lower risk of colorectal cancer (CRC); however, studies showed inconsistent results on which cohort of individuals may benefit most. We performed multivariable logistic regression analysis to systematically test for the interaction between regular use of NSAIDs and other lifestyle and dietary factors on CRC risk among 11,894 cases and 15,999 controls. Fixed-effects meta-analyses were used for stratified analyses across studies for each risk factor and to summarize the estimates from interactions. Regular use of any NSAID, aspirin, or non-aspirin NSAIDs was significantly associated with a lower risk of CRC within almost all subgroups. However, smoking status and BMI were found to modify the NSAID-CRC association. Aspirin use was associated with a 29% lower CRC risk among never-smokers (OR = 0.71; 95% CI: 0.64, 0.79), compared to 19% and 17% lower CRC risk among smokers of pack-years below median (OR = 0.81; 95% CI: 0.71, 0.92) and above median (OR = 0.83; 95% CI: 0.74, 0.94), respectively (p-interaction = 0.048). The association between any NSAID use and CRC risk was also attenuated with increasing BMI (p-interaction = 0.075). Collectively, these results suggest that obese individuals and heavy smokers are unlikely to benefit as much as other groups from the prophylactic effect of aspirin against CRC. Copyright ©2018, American Association for Cancer Research.

  17. The association of TP53 mutations with the resistance of colorectal carcinoma to the insulin-like growth factor-1 receptor inhibitor picropodophyllin

    International Nuclear Information System (INIS)

    Wang, Quan; Wei, Feng; Lv, Guoyue; Li, Chunsheng; Liu, Tongjun; Hadjipanayis, Costas G; Zhang, Guikai; Hao, Chunhai; Bellail, Anita C

    2013-01-01

    There is growing evidence indicating the insulin-like growth factor 1 receptor (IGF-1R) plays a critical role in the progression of human colorectal carcinomas. IGF-1R is an attractive drug target for the treatment of colon cancer. Picropodophyllin (PPP), of the cyclolignan family, has recently been identified as an IGF-1R inhibitor. The aim of this study is to determine the therapeutic response and mechanism after colorectal carcinoma treatment with PPP. Seven colorectal carcinoma cell lines were treated with PPP. Following treatment, cells were analyzed for growth by a cell viability assay, sub-G1 apoptosis by flow cytometry, caspase cleavage and activation of AKT and extracellular signal-regulated kinase (ERK) by western blot analysis. To examine the in vivo therapeutic efficacy of PPP, mice implanted with human colorectal carcinoma xenografts underwent PPP treatment. PPP treatment blocked the phosphorylation of IGF-1R, AKT and ERK and inhibited the growth of TP53 wild-type but not mutated colorectal carcinoma cell lines. The treatment of PPP also induced apoptosis in TP53 wild-type cells as evident by the presence of sub-G1 cells and the cleavage of caspase-9, caspase-3, DNA fragmentation factor-45 (DFF45), poly (ADP-ribose) polymerase (PARP), and X-linked inhibitor of apoptosis protein (XIAP). The loss of BAD phosphorylation in the PPP-treated TP53 wild type cells further suggested that the treatment induced apoptosis through the BAD-mediated mitochondrial pathway. In contrast, PPP treatment failed to induce the phosphorylation of AKT and ERK and caspase cleavage in TP53 mutated colorectal carcinoma cell lines. Finally, PPP treatment suppressed the growth of xenografts derived from TP53 wild type but not mutated colorectal carcinoma cells. We report the association of TP53 mutations with the resistance of treatment of colorectal carcinoma cells in culture and in a xenograft mouse model with the IGF-1R inhibitor PPP. TP53 mutations often occur in colorectal

  18. Management of Colorectal Trauma

    Science.gov (United States)

    2011-01-01

    Although the treatment strategy for colorectal trauma has advanced during the last part of the twentieth century and the result has improved, compared to other injuries, problems, such as high septic complication rates and mortality rates, still exist, so standard management for colorectal trauma is still a controversial issue. For that reason, we designed this article to address current recommendations for management of colorectal injuries based on a review of literature. According to the reviewed data, although sufficient evidence exists for primary repair being the treatment of choice in most cases of nondestructive colon injuries, many surgeons are still concerned about anastomotic leakage or failure, and prefer to perform a diverting colostomy. Recently, some reports have shown that primary repair or resection and anastomosis, is better than a diverting colostomy even in cases of destructive colon injuries, but it has not fully established as the standard treatment. The same guideline as that for colonic injury is applied in cases of intraperitoneal rectal injuries, and, diversion, primary repair, and presacral drainage are regarded as the standards for the management of extraperitoneal rectal injuries. However, some reports state that primary repair without a diverting colostomy has benefit in the treatment of extraperitoneal rectal injury, and presacral drainage is still controversial. In conclusion, ideally an individual management strategy would be developed for each patient suffering from colorectal injury. To do this, an evidence-based treatment plan should be carefully developed. PMID:21980586

  19. Colorectal Cancer Rates by Race and Ethnicity

    Science.gov (United States)

    ... Associated Lung Ovarian Prostate Skin Uterine Cancer Home Colorectal Cancer Rates by Race and Ethnicity Language: English (US) ... Tweet Share Compartir The rate of people getting colorectal cancer or dying from colorectal cancer varies by race ...

  20. Radioimmunodetection of colorectal cancer

    International Nuclear Information System (INIS)

    Kim, E.E.; Deland, F.H.; Casper, S.; Corgan, R.L.; Primus, F.J.; Goldenberg, D.M.

    1980-01-01

    This study examines the accuracy of colorectal cancer radioimmunodetection. Twenty-seven patients with a history of histologically-confirmed colonic or rectal carcinoma received a high-titer, purified goat anti-CEA IgG labelled with 131 I at a total dose of at least 1.0 μCi. Various body views were scanned at 24 and 48 hours after administration of the radioantibody. Three additional cases were evaluated; one had a villous adenoma in the rectum and received the 131 I-labeled anti-CEA IgG, while two colonic carcinoma patients received normal goat IgG labelled with 131 I. All of the 7 cases with primary colorectal cancer showed true-positive tumor localization, while 20 of 25 sites of metastatic colorectal cancer detected by immune scintigraphy were corroborated by other detection measures. The sensitivity of the radioimmunodetection of colorectal cancers (primary and metastatic) was found to be 90% (true-positive rate), the putative specificity (true-negative rate) was 94%, and the apparent overall accuracy of the technique was 93%. Neither the case of a villous adenoma receiving the anti-CEA IgG nor the two cases of colonic cancer receiving normal goat IgG showed tumor radiolocalization. Very high circulating CEA titers did not appear to hinder successful tumor radiolocalization. These findings suggest that in colorectal cancers the method of CEA radioimmunodetection may be of value in preoperatively determining the location and extent of disease, in assessing possible recurrence or spread postoperatively, and in localizing the source of CEA production in patients with rising or elevated CEA titers. An ancilliary benefit could be a more tumor-specific detection test for confirming the findings of other, more conventional diagnostic measures

  1. Human reconstructed skin xenografts on mice to model skin physiology.

    Science.gov (United States)

    Salgado, Giorgiana; Ng, Yi Zhen; Koh, Li Fang; Goh, Christabelle S M; Common, John E

    Xenograft models to study skin physiology have been popular for scientific use since the 1970s, with various developments and improvements to the techniques over the decades. Xenograft models are particularly useful and sought after due to the lack of clinically relevant animal models in predicting drug effectiveness in humans. Such predictions could in turn boost the process of drug discovery, since novel drug compounds have an estimated 8% chance of FDA approval despite years of rigorous preclinical testing and evaluation, albeit mostly in non-human models. In the case of skin research, the mouse persists as the most popular animal model of choice, despite its well-known anatomical differences with human skin. Differences in skin biology are especially evident when trying to dissect more complex skin conditions, such as psoriasis and eczema, where interactions between the immune system, epidermis and the environment likely occur. While the use of animal models are still considered the gold standard for systemic toxicity studies under controlled environments, there are now alternative models that have been approved for certain applications. To overcome the biological limitations of the mouse model, research efforts have also focused on "humanizing" the mice model to better recapitulate human skin physiology. In this review, we outline the different approaches undertaken thus far to study skin biology using human tissue xenografts in mice and the technical challenges involved. We also describe more recent developments to generate humanized multi-tissue compartment mice that carry both a functioning human immune system and skin xenografts. Such composite animal models provide promising opportunities to study drugs, disease and differentiation with greater clinical relevance. Copyright © 2017 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

  2. 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.

  3. Influencia de la dieta y los estilos de vida en el cáncer colorrectal Influence of diet and lifestyle in colorectal cancer

    Directory of Open Access Journals (Sweden)

    J. Solera Albero

    2007-04-01

    ./año también forma parte del grupo de baja incidencia. De las 450 personas seleccionadas, completaron correctamente la encuesta 414 personas, el 92%. Dentro de las variables podemos ver que las que consumen algún tipo de alcohol: cerveza, vino y carajillos tienen una asociación estadísticamente significativa y multiplican por algo más de 1 el riesgo de padecer CCR. En las variables cualitativas podemos observar que dentro de las que tienen asociación estadísticamente significativa, existen unas que disminuyen el riesgo de padecer CCR y otras que lo aumentan. Así podemos ver que disminuye el riesgo de CCR la presencia de patologías asociadas que lo multiplicaría por 0,6, el hacer ejercicio multiplicaría el riesgo de CCR por 0,3, el consumo medio de alcohol lo multiplicaría por 0,5, el consumo de aceite de oliva lo multiplicaría por 0,7 y por último el consumo de agua lo haría por 0,3. Por otra parte aumenta el riesgo de padecer CCR el consumo alto de alcohol que lo multiplicaría por 1,8, el consumo de huevos y tortillas lo multiplicaría por 2,95, el consumo de pasta y arroz por 2,15, el consumo de pescado azul por 1,8, el consumo de embutidos y de carnes por 1,6 y finalmente el tener familiares de primer y segundo grado multiplicaría casi por 3 el riesgo de padecer CCR. Conclusiones: en nuestro estudio resultan factores protectores de CCR: tener alguna enfermedad, hacer ejercicio físico, consumo moderado de alcohol, consumo de aceite de oliva e ingestión de agua. Mientras que actúan como factores predisponentes el consumo alto de alcohol, consumo de huevos y tortillas, consumo de pasta y arroz, consumo de pescado azul, consumo de embutidos y carnes y tener familiares con cáncer.Objective: to assess the relationship between different colorectal cancer risk factors in Albacete province. Material and method: the incidence and prevalence of CC (colorectal cancer in Albacete province during the years from 1992 to 1999 were calculated using data from the

  4. 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.

  5. Intrabilary obstruction by colorectal metastases

    OpenAIRE

    Traeger, Luke; Kiroff, George

    2018-01-01

    Abstract Intrabiliary colorectal metastases are rare. We present a case of an 84-year-old man who developed obstructive jaundice secondary to intrabiliary growth of colorectal metastases. The patient presented with three weeks of jaundice and significant weight loss in the preceding months. The patient’s background included metastatic colorectal carcinoma, with a previous right hemicolectomy and left hepatectomy for liver metastases. A MRCP showed an obstruction of the biliary tract transitio...

  6. 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...... advancements in the field of colorectal cancer....

  7. Endoscopic management of colorectal adenomas.

    Science.gov (United States)

    Meier, Benjamin; Caca, Karel; Fischer, Andreas; Schmidt, Arthur

    2017-01-01

    Colorectal adenomas are well known precursors of invasive adenocarcinoma. Colonoscopy is the gold standard for adenoma detection. Colonoscopy is far more than a diagnostic tool, as it allows effective treatment of colorectal adenomas. Endoscopic resection of colorectal adenomas has been shown to reduce the incidence and mortality of colorectal cancer. Difficult resection techniques are available, such as endoscopic mucosal resection, endoscopic submucosal dissection and endoscopic full-thickness resection. This review aims to provide an overview of the different endoscopic resection techniques and their indications, and summarizes the current recommendations in the recently published guideline of the European Society of Gastrointestinal Endoscopy.

  8. Curcumin-Free Turmeric Exhibits Activity against Human HCT-116 Colon Tumor Xenograft: Comparison with Curcumin and Whole Turmeric

    Science.gov (United States)

    Prasad, Sahdeo; Tyagi, Amit K.; Siddik, Zahid H.; Aggarwal, Bharat B.

    2017-01-01

    Extensive research within last two decades has indicated that curcumin extracted from turmeric (Curcuma longa), exhibits anticancer potential, in part through the modulation of inflammatory pathways. However, the residual antitumor activity of curcumin-free turmeric (CFT) relative to curcumin or turmeric is not well-understood. In the present study, therefore, we determined activities of these agents in both in vitro and in vivo models of human HCT-116 colorectal cancer (CRC). When examined in an in vitro antiproliferative, clonogenic or anti-inflammatory assay system, we found that curcumin was highly active whereas turmeric and CFT had relatively poor activity against CRC cells. However, when examined in vivo at an oral dose of either 100 or 500 mg/kg given to nude mice bearing CRC xenografts, all three preparations of curcumin, turmeric, and CFT similarly suppressed the growth of the xenograft. The effect of CFT on suppression of tumor growth was dose-dependent, with 500 mg/kg tending to be more effective than 100 mg/kg. Interestingly, 100 mg/kg curcumin or turmeric was found to be more effective than 500 mg/kg. When examined in vivo for the expression of biomarkers associated with cell survival (cIAP-1, Bcl-2, and survivin), proliferation (Ki-67 and cyclin D1) and metastasis (ICAM-1 and VEGF), all were down-modulated. These agents also suppressed inflammatory transcription factors (NF-κB and STAT3) in tumor cells. Overall, our results with CFT provide evidence that turmeric must contain additional bioactive compounds other than curcumin that, in contrast to curcumin, exhibit greater anticancer potential in vivo than in vitro against human CRC. Moreover, our study highlights the fact that the beneficial effects of turmeric and curcumin in humans may be more effectively realized at lower doses, whereas CFT could be given at higher doses without loss in favorable activity. PMID:29311914

  9. Curcumin-Free Turmeric Exhibits Activity against Human HCT-116 Colon Tumor Xenograft: Comparison with Curcumin and Whole Turmeric

    Directory of Open Access Journals (Sweden)

    Sahdeo Prasad

    2017-12-01

    Full Text Available Extensive research within last two decades has indicated that curcumin extracted from turmeric (Curcuma longa, exhibits anticancer potential, in part through the modulation of inflammatory pathways. However, the residual antitumor activity of curcumin-free turmeric (CFT relative to curcumin or turmeric is not well-understood. In the present study, therefore, we determined activities of these agents in both in vitro and in vivo models of human HCT-116 colorectal cancer (CRC. When examined in an in vitro antiproliferative, clonogenic or anti-inflammatory assay system, we found that curcumin was highly active whereas turmeric and CFT had relatively poor activity against CRC cells. However, when examined in vivo at an oral dose of either 100 or 500 mg/kg given to nude mice bearing CRC xenografts, all three preparations of curcumin, turmeric, and CFT similarly suppressed the growth of the xenograft. The effect of CFT on suppression of tumor growth was dose-dependent, with 500 mg/kg tending to be more effective than 100 mg/kg. Interestingly, 100 mg/kg curcumin or turmeric was found to be more effective than 500 mg/kg. When examined in vivo for the expression of biomarkers associated with cell survival (cIAP-1, Bcl-2, and survivin, proliferation (Ki-67 and cyclin D1 and metastasis (ICAM-1 and VEGF, all were down-modulated. These agents also suppressed inflammatory transcription factors (NF-κB and STAT3 in tumor cells. Overall, our results with CFT provide evidence that turmeric must contain additional bioactive compounds other than curcumin that, in contrast to curcumin, exhibit greater anticancer potential in vivo than in vitro against human CRC. Moreover, our study highlights the fact that the beneficial effects of turmeric and curcumin in humans may be more effectively realized at lower doses, whereas CFT could be given at higher doses without loss in favorable activity.

  10. Fentanyl inhibits proliferation and invasion of colorectal cancer via β-catenin

    Science.gov (United States)

    Zhang, Xiu-Lai; Chen, Min-Li; Zhou, Sheng-Li

    2015-01-01

    Background and aim: Fentanyl is widely used for relieving pain and narcotizing in cancer patients. However, there are few published reports regarding the effects of fentanyl on tumor control and treatment. Here we investigated the effects of fentanyl on tumor growth and cell invasion in the human colorectal carcinoma (HCT116) cells. Methods: Nude mice xenografts of HCT116 cells were established to assess the inhibition effect on tumor growth by fentanyl. MTT and Transwell were employed to determine the cell survival rate and cell invasion, respectively. MicroRNAs and mRNAs expression were quantified by real-time PCR. β-catenin and matrix metalloproteinases (MMP-2 and MMP-9) expression were assayed by western blotting. β-Catenin-specific small interfering RNA (Si-β-catenin) and miR-182 mimics were transfected in cells to investigate the mechanism underlying the effects of fentanyl on the colorectal tumor and HCT116 cells. Results: Treatment with fentanyl inhibited the tumor growth and HCT116 cells invasion. Fentanyl also downregulated the expression of β-catenin and miR-182 in both xenograft tumors and HCT116 cells, and decreased the protein level of MMP-9 in HCT116 cells. Downregulation of β-Catenin resulted in the decrease of miR-182 expression in colorectal cells. In addition, the overexpression of miR-182 reversed the effect of fentanyl on MMP-9 expression and cell invasion of HCT116 cells. Conclusions: The current study demonstrated that the inhibition of tumor growth and cell invasion in colorectal cancer by fentanyl is probably due to downregulation of miR-182 and MMP-9 expression by β-catenin. PMID:25755709

  11. A Pretargeted Approach for the Multimodal PET/NIRF Imaging of Colorectal Cancer.

    Science.gov (United States)

    Adumeau, Pierre; Carnazza, Kathryn E; Brand, Christian; Carlin, Sean D; Reiner, Thomas; Agnew, Brian J; Lewis, Jason S; Zeglis, Brian M

    2016-01-01

    The complementary nature of positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging makes the development of strategies for the multimodal PET/NIRF imaging of cancer a very enticing prospect. Indeed, in the context of colorectal cancer, a single multimodal PET/NIRF imaging agent could be used to stage the disease, identify candidates for surgical intervention, and facilitate the image-guided resection of the disease. While antibodies have proven to be highly effective vectors for the delivery of radioisotopes and fluorophores to malignant tissues, the use of radioimmunoconjugates labeled with long-lived nuclides such as 89 Zr poses two important clinical complications: high radiation doses to the patient and the need for significant lag time between imaging and surgery. In vivo pretargeting strategies that decouple the targeting vector from the radioactivity at the time of injection have the potential to circumvent these issues by facilitating the use of positron-emitting radioisotopes with far shorter half-lives. Here, we report the synthesis, characterization, and in vivo validation of a pretargeted strategy for the multimodal PET and NIRF imaging of colorectal carcinoma. This approach is based on the rapid and bioorthogonal ligation between a trans -cyclooctene- and fluorophore-bearing immunoconjugate of the huA33 antibody (huA33-Dye800-TCO) and a 64 Cu-labeled tetrazine radioligand ( 64 Cu-Tz-SarAr). In vivo imaging experiments in mice bearing A33 antigen-expressing SW1222 colorectal cancer xenografts clearly demonstrate that this approach enables the non-invasive visualization of tumors and the image-guided resection of malignant tissue, all at only a fraction of the radiation dose created by a directly labeled radioimmunoconjugate. Additional in vivo experiments in peritoneal and patient-derived xenograft models of colorectal carcinoma reinforce the efficacy of this methodology and underscore its potential as an innovative and useful

  12. Imaging of primary and metastatic colorectal carcinoma with monoclonal antibody 791T/36 and the therapeutic potential of antibody-drug conjugates

    International Nuclear Information System (INIS)

    Pimm, M.V.; Armitage, N.C.; Ballantyne, K.; Baldwin, R.W.; Perkins, A.C.; Durrant, L.G.; Garnett, M.C.; Hardcastle, J.D.

    1987-01-01

    Monoclonal antibody 791T/36, prepared against a tumor-associated 72,000 dalton glycoprotein, reacted with cells from primary and metastatic colorectal carcinomas. I-131 or In-111-labelled antibody localized in xenografts of colorectal carcinomas established from in vitro clonogenic populations. Clinically, with I-131-labelled antibody, 8/11 colonic tumors imaged positively. Imaging was negative in four patients with benign colon disease. 5/11 rectal tumors were positively imaged, but excreted I-131 in the bladder obscured tumors in several studies. In-111-labelled antibody gave superior images and positively imaged primary and metastatic sites in 13/14 patients. Prospectively in the detection of recurrent disease, I-131 or In-111-antibody detected 29/33 separate sites in 24 patients. Seven negative patients remain disease free. There were 3 false positives; overall sensitivity was 88%, with 70% specificity. Specific localization of radiolabel was confirmed immunochemically and by counting radioactivity in resected specimens. Antibody conjugates with methotrexate, vindesine and daunomycin retained drug activity and antibody function, including xenograft localization and conjugates were therapeutically effective against xenografts. 791T/36 antibody has potential for immunodetection of primary and recurrent colorectal carcinoma and for targeting of therapeutic agents

  13. Reduced miR-433 expression is associated with advanced stages and early relapse of colorectal cancer and restored miR-433 expression suppresses the migration, invasion and proliferation of tumor cells in vitro and in nude mice.

    Science.gov (United States)

    Zhang, Jian; Zhang, Lei; Zhang, Tong; Dong, Xin-Min; Zhu, Yu; Chen, Long-Hua

    2018-05-01

    The expression of microRNA (miR-433) is altered in various types of human cancer. The present study analyzed the prognostic and biological value of miR-433 expression in colorectal cancer using reverse transcription-quantitative polymerase chain reaction in 125 colorectal tissue specimens (including a test cohort of 40 cases of paired colorectal cancer and adjacent normal mucosae and a confirmation cohort of 85 cases of stage I-III colorectal cancer). In vitro and nude mouse xenograft experiments were subsequently used to assess the effects of miR-433 expression on the regulation of colorectal cancer cell proliferation, adhesion, migration, and invasion. The data indicated that miR-433 expression was significantly downregulated in colorectal cancer tissues in the test and confirmation patient cohorts and that low miR-433 expression was associated with advanced tumor stage and early relapse. Furthermore, the restoration of miR-433 expression was able to significantly inhibit the proliferation of tumor cells by inducing G1-S cell cycle arrest, suppressing cyclinD1 and CDK4 expression, and markedly inhibited the migratory and invasive capacities of tumor cells in vitro . The restoration of miR-433 expression or liposome-based delivery of miR-433 mimics suppressed the growth of colorectal cancer cell xenografts in nude mice. In conclusion, miR-433 may be a putative tumor suppressor in colorectal cancer, and the detection of low miR-433 expression will be investigated in further studies as a putative biomarker for the detection of early relapse in patients with colorectal cancer.

  14. Clinical Correlates of Health Preference and Generic Health-Related Quality of Life in Patients with Colorectal Neoplasms

    OpenAIRE

    Wong, Carlos K. H.; Lam, Cindy L. K.; Poon, Jensen T. C.; Kwong, Dora L. W.

    2013-01-01

    BACKGROUND: The aims of the study were to assess the health preference and health-related quality of life (HRQOL) in patients with colorectal neoplasms (CRN), and to determine the clinical correlates that significantly influence the HRQOL of patients. METHODS: Five hundred and fifty-four CRN patients, inclusive of colorectal polyp or cancer, who attended the colorectal specialist outpatient clinic at Queen Mary Hospital in Hong Kong between October 2009 and July 2010, were included. Patients ...

  15. PET imaging of HER1-expressing xenografts in mice with 86Y-CHX-A''-DTPA-cetuximab

    International Nuclear Information System (INIS)

    Nayak, Tapan K.; Regino, Celeste A.S.; Milenic, Diane E.; Garmestani, Kayhan; Baidoo, Kwamena E.; Brechbiel, Martin W.; Wong, Karen J.; Szajek, Lawrence P.

    2010-01-01

    Cetuximab is a recombinant, human/mouse chimeric IgG 1 monoclonal antibody that binds to the epidermal growth factor receptor (EGFR/HER1). Cetuximab is approved for the treatment of patients with HER1-expressing metastatic colorectal cancer. Limitations in currently reported radiolabeled cetuximab for PET applications prompted the development of 86 Y-CHX-A''-DTPA-cetuximab as an alternative for imaging HER1-expressing cancer. 86 Y-CHX-A''-DTPA-cetuximab can also serve as a surrogate marker for 90 Y therapy. Bifunctional chelate, CHX-A''-DTPA was conjugated to cetuximab and radiolabeled with 86 Y. In vitro immunoreactivity was assessed in HER1-expressing A431 cells. In vivo biodistribution, PET imaging and noncompartmental pharmacokinetics were performed in mice bearing HER1-expressing human colorectal (LS-174T and HT29), prostate (PC-3 and DU145), ovarian (SKOV3) and pancreatic (SHAW) tumor xenografts. Receptor blockage was demonstrated by coinjection of either 0.1 or 0.2 mg cetuximab. 86 Y-CHX-A''-DTPA-cetuximab was routinely prepared with a specific activity of 1.5-2 GBq/mg and in vitro cell-binding in the range 65-75%. Biodistribution and PET imaging studies demonstrated high HER1-specific tumor uptake of the radiotracer and clearance from nonspecific organs. In LS-174T tumor-bearing mice injected with 86 Y-CHX-A''-DTPA-cetuximab alone, 86 Y-CHX-A''-DTPA-cetuximab plus 0.1 mg cetuximab or 0.2 mg cetuximab, the tumor uptake values at 3 days were 29.3 ± 4.2, 10.4 ± 0.5 and 6.4 ± 0.3%ID/g, respectively, demonstrating dose-dependent blockage of the target. Tumors were clearly visualized 1 day after injecting 3.8-4.0 MBq 86 Y-CHX-A''-DTPA-cetuximab. Quantitative PET revealed the highest tumor uptake in LS-174T (29.55 ± 2.67%ID/cm 3 ) and the lowest tumor uptake in PC-3 (15.92 ± 1.55%ID/cm 3 ) xenografts at 3 days after injection. Tumor uptake values quantified by PET were closely correlated (r 2 = 0.9, n = 18) with values determined by biodistribution studies

  16. Colorectal Cancer Screening

    OpenAIRE

    Quintero, Enrique; Saito, Yutaka; Hassan, Cessare; Senore, Carlo

    2012-01-01

    Colorectal cancer, which is the leading cancer in Singapore, can be prevented by increased use of screening and polypectomy. A range of screening strategies such as stool-based tests, flexible sigmoidoscopy, colonoscopy and computed tomography colonography are available, each with different strengths and limitations. Primary care physicians should discuss appropriate screening modalities with their patients, tailored to their individual needs. Physicians, patients and the government should wo...

  17. FGFR2 amplification is predictive of sensitivity to regorafenib in gastric and colorectal cancers in vitro.

    Science.gov (United States)

    Cha, Yongjun; Kim, Hwang-Phill; Lim, Yoojoo; Han, Sae-Won; Song, Sang-Hyun; Kim, Tae-You

    2018-03-24

    Although regorafenib has demonstrated survival benefits in patients with metastatic colorectal and gastrointestinal stromal tumors, no proven biomarker has been identified for predicting sensitivity to regorafenib. Here, we investigated preclinical activity of regorafenib in gastric and colorectal cancer cells to identify genetic alterations associated with sensitivity to regorafenib. Mutation profiles and copy number assays of regorafenib target molecules indicated that amplification of FGFR2 was the only genetic alteration associated with in vitro sensitivity to regorafenib. Regorafenib effectively inhibited phosphorylation of FGFR2 and its downstream signaling molecules in a dose-dependent manner and selectively in FGFR2 amplified cells. Regorafenib induced G1 arrest (SNU-16, KATO-III) and apoptosis (NCI-H716), however, no significant changes were seen in cell lines without FGFR2 amplification. In SNU-16 mice xenografts, regorafenib significantly inhibited tumor growth, proliferation, and FGFR signaling compared to treatment with control vehicle. Regorafenib effectively abrogates activated FGFR2 signaling in FGFR2 amplified gastric and colorectal cancer and therefore, might be considered for integration into treatment in patients with FGFR2 amplified gastric and colorectal cancers. This article is protected by copyright. All rights reserved. Molecular Oncology (2018) © 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

  18. Four jointed box 1 promotes angiogenesis and is associated with poor patient survival in colorectal carcinoma.

    Directory of Open Access Journals (Sweden)

    Nicole T Al-Greene

    Full Text Available Angiogenesis, the recruitment and re-configuration of pre-existing vasculature, is essential for tumor growth and metastasis. Increased tumor vascularization often correlates with poor patient outcomes in a broad spectrum of carcinomas. We identified four jointed box 1 (FJX1 as a candidate regulator of tumor angiogenesis in colorectal cancer. FJX1 mRNA and protein are upregulated in human colorectal tumor epithelium as compared with normal epithelium and colorectal adenomas, and high expression of FJX1 is associated with poor patient prognosis. FJX1 mRNA expression in colorectal cancer tissues is significantly correlated with changes in known angiogenesis genes. Augmented expression of FJX1 in colon cancer cells promotes growth of xenografts in athymic mice and is associated with increased tumor cell proliferation and vascularization. Furthermore, FJX1 null mice develop significantly fewer colonic polyps than wild-type littermates after combined dextran sodium sulfate (DSS and azoxymethane (AOM treatment. In vitro, conditioned media from FJX1 expressing cells promoted endothelial cell capillary tube formation in a HIF1-α dependent manner. Taken together our results support the conclusion that FJX1 is a novel regulator of tumor progression, due in part, to its effect on tumor vascularization.

  19. Use of preoperative bowel preparation in elective colorectal surgery in Denmark remains high

    DEFF Research Database (Denmark)

    Andersen, Julie; Thorup, Jens; Wille-Jørgensen, Peer

    2011-01-01

    Previous studies have shown that preoperative bowel preparation does not influence the frequency of postoperative complications after elective open colonic resections. The Danish Colorectal Cancer Group (DCCG) recommends that mechanical bowel preparation (MBP) should be omitted prior to elective...

  20. 31P-NMR spectroscopy in measurements of physiological parameters and response to therapy of human melanoma xenografts

    International Nuclear Information System (INIS)

    Olsen, Dag Rune

    1999-01-01

    The aim of the study was to investigate whether ''31P-NMR spectroscopy can be utilized in prediction and monitoring of response to therapy or tumours. The specific aims were: 1) To investigate possible correlations between on the one hand bio energetics status, phospholipids resonance ratios, intracellular pH and phosphorus T 1 s and on the other hand tumour blood supply and oxygenation, tumour proliferation and necrotic fraction across tumour lines. 2) Reveal possible correlations between changes in tumour bio energetics status and phosphorus T 1 s and the changes in tumour blood flow, tumour oxygenation and necrotic fraction. 3) To investigate whether irradiation and hyperthermia treatment of tumours affect bio energetics status and phosphorus T 1 s. 4) To identify the tumour physiological factors that is effected by the treatment and influence the bio energetics status and phosphorus T 1 s. The results are presented in 8 papers with titles: 1)''31P-nuclear magnetic resonance spectroscopy in vivo of six human melanoma zeno graft lines: Tumour bio energetic status and blood supply. 2) ''31P NMR spectroscopy studies of phospholipid metabolism in human melanoma xenograft lines differing in rate of tumour cell proliferation. 3) ''31P-nuclear magnetic resonance spectroscopy in vivo of four human melanoma xenograft lines: Spin-lattice relaxation times. 4) Effect of melanin on phosphorus T 1 s in human melanoma xenografts studied by ''31P MRS 5) Spin-lattice relaxation time of inorganic phosphate in human tumour xenografts measured in vivo by ''31P-magnetic resonance spectroscopy influence of oxygen tension. 6) Effects of hyperthermia on bio energetic status and phosphorus T 1 s in human melanoma xenografts monitored by ''31P-MRS. 7) Monitoring of tumour reoxygenation following irradiation by ''31P magnetic resonance spectroscopy an experimental study of human melanoma xenografts. 8) Radiation-induced changes in phosphorus T 1 values in human melanoma xenografts studied

  1. Targeting of human glioma xenografts in vivo utilizing radiolabeled antibodies

    International Nuclear Information System (INIS)

    Williams, J.A.; Wessels, B.W.; Wharam, M.D.; Order, S.E.; Wanek, P.M.; Poggenburg, J.K.; Klein, J.L.

    1990-01-01

    Radiolabeled antibodies provide a potential basis for selective radiotherapy of human gliomas. We have measured tumor targeting by radiolabeled monoclonal and polyclonal antibodies directed against neuroectodermal and tumor-associated antigens in nude mice bearing human glioma xenografts. Monoclonal P96.5, a mouse IgG2a immunoglobulin, defines an epitope of a human melanoma cell surface protein, and specifically binds the U-251 human glioma as measured by immunoperoxidase histochemistry. 111In-radiolabeled P96.5 specifically targets the U-251 human glioma xenograft and yields 87.0 microCuries (microCi) of tumor activity per gram per 100 microCi injected activity compared to 4.5 microCi following administration of radiolabeled irrelevant monoclonal antibody. Calculations of targeting ratios demonstrate deposited dose to be 11.6 times greater with radiolabeled P96.5 administration compared to irrelevant monoclonal antibody. The proportion of tumor dose found in normal organs is less than 10%, further supporting specific targeting of the human glioma xenograft by this antibody. Monoclonal antibody ZME018, which defines a second melanoma-associated antigen, and polyclonal rabbit antiferritin, which defines a tumor-associated antigen, demonstrate positive immunoperoxidase staining of the tumor, but comparatively decreased targeting. When compared to the 111In-radiolabeled antibody, 90Y-radiolabeled P96.5 demonstrates comparable tumor targeting and percentages of tumor dose found in normal organs. To test the therapeutic potential of 90Y-radiolabeled P96.5, tumors and normal sites were implanted with miniature thermoluminescent dosimeters (TLD). Seven days following administration of 100 microCi 90Y-radiolabeled P96.5, average absorbed doses of 3770, 980, 353, and 274 cGy were observed in tumor, liver, contralateral control site, and total body, respectively

  2. The dutch surgical colorectal audit

    NARCIS (Netherlands)

    Leersum, N.J. van; Snijders, H.S.; Henneman, D.; Kolfschoten, N.E.; Gooiker, G.A.; Berge, M.G. Ten; Eddes, E.H.; Wouters, M.W.; Tollenaar, R.A.E.M.; Bemelman, W.A.; Dam, R.M. van; Elferink, M.A.; Karsten, T.M.; Krieken, J.H. van; Lemmens, V.E.; Rutten, H.J.; Manusama, E.R.; Velde, C.J. van de; Meijerink, W.J.H.J.; Wiggers, T.; Harst, E. van der; Dekker, J.W.T.; Boerma, D.

    2013-01-01

    INTRODUCTION: In 2009, the nationwide Dutch Surgical Colorectal Audit (DSCA) was initiated by the Association of Surgeons of the Netherlands (ASN) to monitor, evaluate and improve colorectal cancer care. The DSCA is currently widely used as a blueprint for the initiation of other audits, coordinated

  3. Colorectal Cancer—Patient Version

    Science.gov (United States)

    Colorectal cancer often begins as a growth called a polyp inside the colon or rectum. Finding and removing polyps can prevent colorectal cancer. Start here to find information on colon and rectal cancer treatment, causes and prevention, screening, research, and statistics.

  4. The Dutch surgical colorectal audit

    NARCIS (Netherlands)

    van Leersum, N. J.; Snijders, H. S.; Henneman, D.; Kolfschoten, N. E.; Gooiker, G. A.; ten Berge, M. G.; Eddes, E. H.; Wouters, M. W. J. M.; Tollenaar, R. A. E. M.; Bemelman, W. A.; van Dam, R. M.; Elferink, M. A.; Karsten, Th M.; van Krieken, J. H. J. M.; Lemmens, V. E. P. P.; Rutten, H. J. T.; Manusama, E. R.; van de Velde, C. J. H.; Meijerink, W. J. H. J.; Wiggers, Th; van der Harst, E.; Dekker, J. W. T.; Boerma, D.

    2013-01-01

    In 2009, the nationwide Dutch Surgical Colorectal Audit (DSCA) was initiated by the Association of Surgeons of the Netherlands (ASN) to monitor, evaluate and improve colorectal cancer care. The DSCA is currently widely used as a blueprint for the initiation of other audits, coordinated by the Dutch

  5. Aortic valve replacement with the Biocor PSB stentless xenograft.

    Science.gov (United States)

    Bertolini, P; Luciani, G B; Vecchi, B; Pugliese, P; Mazzucco, A

    1998-08-01

    The midterm clinical results after aortic valve replacement with the Biocor PSB stentless xenograft on all patients operated between October 1992 and October 1996 were reviewed. One hundred six patients, aged 70+/-6 years, had aortic valve replacement for aortic stenosis (67%), regurgitation (11%), or both (22%). Associated procedures were done in 49 patients (46%), including coronary artery bypass in 30 patients, mitral valve repair/replacement in 16, and ascending aorta replacement in 5 patients. Aortic cross-clamp and cardiopulmonary bypass times were 96+/-24 and 129+/-31 minutes, respectively. There were 3 (3%) early deaths due to low output (2 patients) and cerebrovascular accident (1 patient). Follow-up of survivors ranged from 6 to 66 months (mean, 39+/-14 months). Survival was 94%+/-2% and 90%+/-3% at 1 and 5 years. There were 5 late deaths due to cardiac cause (2), cancer (2), and pulmonary embolism (1 patient). No patient had structural valve deterioration, whereas 100% and 95%+/-3% were free from valve-related events at 1 and 5 years. There were two reoperations due to narrowing of the left coronary ostium and endocarditis, with an actuarial freedom from reoperation of 99%+/-1% and 98+/-1% at 1 and 5 years, respectively. Functional results demonstrated a mean peak transprosthetic gradient of 16+/-12 mm Hg, with only 1 patient (1%) with a 55 mm Hg gradient. No cases of valve regurgitation greater than mild were recorded at follow-up. Assessment of New York Heart Association functional class demonstrated a significant improvement (2.9+/-0.6 versus 1.4+/-0.7; p=0.01). All patients were free from anticoagulation. Aortic valve replacement using the Biocor PSB stentless xenograft offers excellent midterm survival, negligible valve deterioration, and a very low rate of valve-related events, which are comparable to estimates reported with other models of stentless xenografts and currently available stented xenografts. Hemodynamic performance is favorable and

  6. Exercise and Low-Dose Ibuprofen for Cognitive Impairment in Colorectal Cancer Patients Receiving Chemotherapy

    Science.gov (United States)

    2018-03-13

    Cognitive Impairment; Stage 0 Colorectal Cancer; Stage I Colorectal Cancer; Stage II Colorectal Cancer; Stage IIA Colorectal Cancer; Stage IIB Colorectal Cancer; Stage IIC Colorectal Cancer; Stage III Colorectal Cancer; Stage IIIA Colorectal Cancer; Stage IIIB Colorectal Cancer; Stage IIIC Colorectal Cancer

  7. Radiosensitization by SAHA in Experimental Colorectal Carcinoma Models-In Vivo Effects and Relevance of Histone Acetylation Status

    International Nuclear Information System (INIS)

    Folkvord, Sigurd; Ree, Anne Hansen; Furre, Torbjorn; Halvorsen, Thomas; Flatmark, Kjersti

    2009-01-01

    Purpose: Histone deacetylase inhibitors are being evaluated as antitumor agents in ongoing clinical trials, and promising preclinical results, combined with favorable toxicity profiles, have rendered the drugs as interesting candidates for combination with other treatment modalities, such as radiotherapy. The aim of the present study was to evaluate the radiosensitizing properties of suberoylanilide hydroxamic acid (SAHA) and the possible requirement of histone hyperacetylation at radiation exposure. Methods and materials: Radiosensitization by SAHA was assessed in a colorectal carcinoma cell line and in two colorectal xenograft models by analysis of clonogenic survival and tumor growth delay, respectively. Histone acetylation status at radiation exposure was evaluated by Western blot. Results: In vitro, radiosensitization was demonstrated when cells were preincubated with SAHA, and, in the xenografts, tumor growth was delayed when the mice were treated with fractionated radiation combined with daily SAHA injections compared with radiation alone. Surprisingly, the SAHA-dependent growth delay was still present when radiation was delivered at restored baseline acetylation levels compared with maximal histone hyperacetylation. Conclusion: SAHA was an effective radiosensitizer in experimental colorectal carcinoma models, suggesting that histone deacetylase inhibition might constitute a valuable supplement to current multimodal treatment strategies in rectal cancer. The presence of histone hyperacetylation at radiation was not required to obtain an increased radiation response, questioning the validity of using histone hyperacetylation as a molecular marker for radiosensitivity.

  8. Radiotherapy and chemotherapy change vessel tree geometry and metastatic spread in a small cell lung cancer xenograft mouse tumor model.

    Directory of Open Access Journals (Sweden)

    Thorsten Frenzel

    Full Text Available Tumor vasculature is critical for tumor growth, formation of distant metastases and efficiency of radio- and chemotherapy treatments. However, how the vasculature itself is affected during cancer treatment regarding to the metastatic behavior has not been thoroughly investigated. Therefore, the aim of this study was to analyze the influence of hypofractionated radiotherapy and cisplatin chemotherapy on vessel tree geometry and metastasis formation in a small cell lung cancer xenograft mouse tumor model to investigate the spread of malignant cells during different treatments modalities.The biological data gained during these experiments were fed into our previously developed computer model "Cancer and Treatment Simulation Tool" (CaTSiT to model the growth of the primary tumor, its metastatic deposit and also the influence on different therapies. Furthermore, we performed quantitative histology analyses to verify our predictions in xenograft mouse tumor model.According to the computer simulation the number of cells engrafting must vary considerably to explain the different weights of the primary tumor at the end of the experiment. Once a primary tumor is established, the fractal dimension of its vasculature correlates with the tumor size. Furthermore, the fractal dimension of the tumor vasculature changes during treatment, indicating that the therapy affects the blood vessels' geometry. We corroborated these findings with a quantitative histological analysis showing that the blood vessel density is depleted during radiotherapy and cisplatin chemotherapy. The CaTSiT computer model reveals that chemotherapy influences the tumor's therapeutic susceptibility and its metastatic spreading behavior.Using a system biological approach in combination with xenograft models and computer simulations revealed that the usage of chemotherapy and radiation therapy determines the spreading behavior by changing the blood vessel geometry of the primary tumor.

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

    Directory of Open Access Journals (Sweden)

    Adrian Tulin

    2018-04-01

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

  10. CP-31398 prevents the growth of p53-mutated colorectal cancer cells in vitro and in vivo.

    Science.gov (United States)

    He, Xingxing; Kong, Xinjuan; Yan, Junwei; Yan, Jingjun; Zhang, Yunan; Wu, Qian; Chang, Ying; Shang, Haitao; Dou, Qian; Song, Yuhu; Liu, Fang

    2015-03-01

    Rescuing the function of mutant p53 protein is an attractive cancer therapeutic strategy. Small molecule CP-31398 was shown to restore mutant p53 tumor suppressor functions in cancer cells. Here, we determined the effects of CP-31398 on the growth of p53-mutated colorectal cancer (CRC) cells in vitro and in vivo. CRC cells which carry p53 mutation in codon 273 were treated with CP-31398 and the control, and the effects of CP-31398 on cell cycle, cell apoptosis, and proliferation were determined. The expression of p53-responsive downstream genes was evaluated by quantitative reverse transcriptase PCR (RT-PCR) and Western blot. CP-31398 was administrated into xenograft tumors created by the inoculation of HT-29 cells, and then the effect of CP-31398 on the growth of xenograft tumors was examined. CP-31398 induced p53 downstream target molecules in cultured HT-29 cells, which resulted in the inhibition of CRC cell growth assessed by the determination of cell cycle, apoptosis, and cell proliferation. In xenograft tumors, CP-31398 modulated the expression of Bax, Bcl-2, caspase 3, cyclin D, and Mdm2 and then blocked the growth of xenograft tumors. CP-31398 would be developed as a therapeutic candidate for p53-mutated CRC due to the restoration of mutant p53 tumor suppressor functions.

  11. Vasculature analysis of patient derived tumor xenografts using species-specific PCR assays: evidence of tumor endothelial cells and atypical VEGFA-VEGFR1/2 signalings

    International Nuclear Information System (INIS)

    Bieche, Ivan; Marangoni, Elisabetta; Roman-Roman, Sergio; Decaudin, Didier; Dangles-Marie, Virginie; Vacher, Sophie; Vallerand, David; Richon, Sophie; Hatem, Rana; De Plater, Ludmilla; Dahmani, Ahmed; Némati, Fariba; Angevin, Eric

    2014-01-01

    Tumor endothelial transdifferentiation and VEGFR1/2 expression by cancer cells have been reported in glioblastoma but remain poorly documented for many other cancer types. To characterize vasculature of patient-derived tumor xenografts (PDXs), largely used in preclinical anti-angiogenic assays, we designed here species-specific real-time quantitative RT-PCR assays. Human and mouse PECAM1/CD31, ENG/CD105, FLT1/VEGFR1, KDR/VEGFR2 and VEGFA transcripts were analyzed in a large series of 150 PDXs established from 8 different tumor types (53 colorectal, 14 ovarian, 39 breast and 15 renal cell cancers, 6 small cell and 5 non small cell lung carcinomas, 13 cutaneous melanomas and 5 glioblastomas) and in two bevacizumab-treated non small cell lung carcinomas xenografts. As expected, mouse cell proportion in PDXs -evaluated by quantifying expression of the housekeeping gene TBP- correlated with all mouse endothelial markers and human VEGFA RNA levels. More interestingly, we observed human PECAM1/CD31 and ENG/CD105 expression in all tumor types, with higher rate in glioblastoma and renal cancer xenografts. Human VEGFR expression profile varied widely depending on tumor types with particularly high levels of human FLT1/VEGFR1 transcripts in colon cancers and non small cell lung carcinomas, and upper levels of human KDR/VEGFR2 transcripts in non small cell lung carcinomas. Bevacizumab treatment induced significant low expression of mouse Pecam1/Cd31, Eng/Cd105, Flt1/Vegfr1 and Kdr/Vefr2 while the human PECAM1/CD31 and VEGFA were upregulated. Taken together, our results strongly suggest existence of human tumor endothelial cells in all tumor types tested and of both stromal and tumoral autocrine VEGFA-VEGFR1/2 signalings. These findings should be considered when evaluating molecular mechanisms of preclinical response and resistance to tumor anti-angiogenic strategies

  12. Human pancreatic cancer xenografts recapitulate key aspects of cancer cachexia.

    Science.gov (United States)

    Delitto, Daniel; Judge, Sarah M; Delitto, Andrea E; Nosacka, Rachel L; Rocha, Fernanda G; DiVita, Bayli B; Gerber, Michael H; George, Thomas J; Behrns, Kevin E; Hughes, Steven J; Wallet, Shannon M; Judge, Andrew R; Trevino, Jose G

    2017-01-03

    Cancer cachexia represents a debilitating syndrome that diminishes quality of life and augments the toxicities of conventional treatments. Cancer cachexia is particularly debilitating in patients with pancreatic cancer (PC). Mechanisms responsible for cancer cachexia are under investigation and are largely derived from observations in syngeneic murine models of cancer which are limited in PC. We evaluate the effect of human PC cells on both muscle wasting and the systemic inflammatory milieu potentially contributing to PC-associated cachexia. Specifically, human PC xenografts were generated by implantation of pancreatic cancer cells, L3.6pl and PANC-1, either in the flank or orthotopically within the pancreas. Mice bearing orthotopic xenografts demonstrated significant muscle wasting and atrophy-associated gene expression changes compared to controls. Further, despite the absence of adaptive immunity, splenic tissue from orthotopically engrafted mice demonstrated elevations in several pro-inflammatory cytokines associated with cancer cachexia, including TNFα, IL1β, IL6 and KC (murine IL8 homologue), when compared to controls. Therefore, data presented here support further investigation into the complexity of cancer cachexia in PC to identify potential targets for this debilitating syndrome.

  13. Effect of onion flavonoids on colorectal cancer with hyperlipidemia: an in vivo study

    Directory of Open Access Journals (Sweden)

    He Y

    2014-01-01

    Full Text Available Yongshan He,1,* Heiying Jin,1,* Wei Gong,2,* Chunxia Zhang,1 Acheng Zhou1 1National Center of Colorectal Surgery, Third Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, People's Republic of China; 2Department of Surgery, Jiangyin Hospital of Traditional Chinese Medicine, Jiangyin, People's Republic of China *These authors contributed equally to this work Objectives: This study aims to find the effect of onion's extraction on the colorectal cancer with hyperlipidemia. Method: We established a hyperlipidemia-subcutaneously heterotopic colorectal cancer orthotopic transplant model and fed mice a high fat diet and performing transplantation. Animal models were treated with capecitabine and/or simvastatin and low-, middle-, high- dose of onion's extraction and both tumor growth rate and blood lipid levels were monitored. Results: We found that colorectal cancer in onion's extraction groups was significantly inhibited, and the effect of high dose of onion's extraction was equivalent to capecitabine. Onion's extraction effectively decreased levels of apoB and TC. Conclusion: Our study established a hyperlipidemia colon tumor model involving subcutaneous colon translocation and orthotopic transplantation, this model was an ideal research model for mutual influence of hyperlipidemia and colorectal cancer. Onion's extraction could inhibit the proliferation of colorectal cancer; the function of the high-dose of onion's extraction was fairly to capecitabine, which provided a new direction in protecting and treating colorectal cancer. Keywords: colorectal cancer, hyperlipidemia, onion flavonoids, capecitabine, simvastatin

  14. Investigation of the roles of exosomes in colorectal cancer liver metastasis.

    Science.gov (United States)

    Wang, Xia; Ding, Xiaoling; Nan, Lijuan; Wang, Yiting; Wang, Jing; Yan, Zhiqiang; Zhang, Wei; Sun, Jihong; Zhu, Wei; Ni, Bing; Dong, Suzhen; Yu, Lei

    2015-05-01

    The leading cause of death among cancer patients is tumor metastasis. Tumor-derived exosomes are emerging as mediators of metastasis. In the present study, we demonstrated that exosomes play a pivotal role in the metastatic progression of colorectal cancer. First, a nude mouse model of colorectal cancer liver metastasis was established and characterized. Then, we demonstrated that exosomes from a highly liver metastatic colorectal cancer cell line (HT-29) could significantly increase the metastatic tumor burden and distribution in the mouse liver of Caco-2 colorectal cancer cells, which ordinarily exhibit poor liver metastatic potential. We further investigated the mechanisms by which HT-29-derived-exosomes influence the liver metastasis of colorectal cancer and found that mice treated with HT-29-derived exosomes had a relatively higher level of CXCR4 in the metastatic microenvironment, indicating that exosomes may promote colorectal cancer metastasis by recruiting CXCR4-expressing stromal cells to develop a permissive metastatic microenvironment. Finally, the migration of Caco-2 cells was significantly increased following treatment with HT-29-derived exosomes in vitro, further supporting a role for exosomes in modulating colorectal tumor-derived liver metastasis. The data from the present study may facilitate further translational medicine research into the prevention and treatment of colorectal cancer liver metastasis.

  15. Helicobacter pylori and colorectal neoplasia: Is there a causal link?

    Science.gov (United States)

    Papastergiou, Vasilios; Karatapanis, Stylianos; Georgopoulos, Sotirios D

    2016-01-01

    Ever since Helicobacter pylori (H. pylori) was recognized as an infectious cause of gastric cancer, there has been increasing interest in examining its potential role in colorectal carcinogenesis. Data from case-control and cross-sectional studies, mostly relying on hospital-based samples, and several meta-analyses have shown a positive statistical relationship between H. pylori infection and colorectal neoplasia. However, the possibility exists that the results have been influenced by bias, including the improper selection of patients and disparities with respect to potential confounders. While the evidence falls short of a definitive causal link, it appears that infection with H. pylori/H. pylori-related gastritis is associated with an increased, although modest, risk of colorectal adenoma and cancer. The pathogenic mechanisms responsible for this association remain uncertain. H. pylori has been detected in colorectal malignant tissues; however, the possibility that H. pylori is a direct activator of colonic carcinogenesis remains purely hypothetical. On the other hand, experimental data have indicated a series of potential oncogenic interactions between these bacteria and colorectal mucosa, including induction and perpetuation of inflammatory responses, alteration of gut microflora and release of toxins and/or hormonal mediators, such as gastrin, which may contribute to tumor formation. PMID:26811614

  16. Genetic subclone architecture of tumor clone-initiating cells in colorectal cancer.

    Science.gov (United States)

    Giessler, Klara M; Kleinheinz, Kortine; Huebschmann, Daniel; Balasubramanian, Gnana Prakash; Dubash, Taronish D; Dieter, Sebastian M; Siegl, Christine; Herbst, Friederike; Weber, Sarah; Hoffmann, Christopher M; Fronza, Raffaele; Buchhalter, Ivo; Paramasivam, Nagarajan; Eils, Roland; Schmidt, Manfred; von Kalle, Christof; Schneider, Martin; Ulrich, Alexis; Scholl, Claudia; Fröhling, Stefan; Weichert, Wilko; Brors, Benedikt; Schlesner, Matthias; Ball, Claudia R; Glimm, Hanno

    2017-07-03

    A hierarchically organized cell compartment drives colorectal cancer (CRC) progression. Genetic barcoding allows monitoring of the clonal output of tumorigenic cells without prospective isolation. In this study, we asked whether tumor clone-initiating cells (TcICs) were genetically heterogeneous and whether differences in self-renewal and activation reflected differential kinetics among individual subclones or functional hierarchies within subclones. Monitoring genomic subclone kinetics in three patient tumors and corresponding serial xenografts and spheroids by high-coverage whole-genome sequencing, clustering of genetic aberrations, subclone combinatorics, and mutational signature analysis revealed at least two to four genetic subclones per sample. Long-term growth in serial xenografts and spheroids was driven by multiple genomic subclones with profoundly differing growth dynamics and hence different quantitative contributions over time. Strikingly, genetic barcoding demonstrated stable functional heterogeneity of CRC TcICs during serial xenografting despite near-complete changes in genomic subclone contribution. This demonstrates that functional heterogeneity is, at least frequently, present within genomic subclones and independent of mutational subclone differences. © 2017 Giessler et al.

  17. Metastatic paediatric colorectal carcinoma.

    LENUS (Irish Health Repository)

    Woods, R

    2012-03-01

    A 16-year-old girl presented to our unit with crampy abdominal pain, change in bowel habit, a subjective impression of weight loss and a single episode of haematochezia. She was found to have a rectosigmoid adenocarcinoma and proceeded to laparoscopic anterior resection, whereupon peritoneal metastases were discovered. She received chemotherapy and is alive and well ten month later with no radiological evidence of disease. Colorectal carcinoma is rare in the paediatric population but is increasing in incidence. Early diagnosis is critical to enable optimal outcomes.

  18. Diagnosis of colorectal tumors

    International Nuclear Information System (INIS)

    Vogl, T.J.; Pegios, W.; Jacobi, V.; Schaefer, S.; Abolmaali, N.; Luboldt, W.

    2003-01-01

    With the introduction of multislice CT extensive volumetric data sets can be quickly acquired in high spatial resolution. The high spatial resolution reduces partial volume effects and enables multiplanar reconstructions. Regarding the colorectum this means that the colon can be assessed if the colon is sufficiently cleaned and distended, and that transmural infiltration of colorectal carcinoma and liver metastases can be better detected. T-staging of colon cancer is less important than T-staging of rectal cancer. Based on the higher contrast MRI is superior to CT in T-staging of rectal cancer and in the differentiation between scarring tissue and recurrence of carcinoma. (orig.) [de

  19. Utility of Glioblastoma Patient-Derived Orthotopic Xenografts in Drug Discovery and Personalized Therapy

    Directory of Open Access Journals (Sweden)

    Michele Patrizii

    2018-02-01

    Full Text Available Despite substantial effort and resources dedicated to drug discovery and development, new anticancer agents often fail in clinical trials. Among many reasons, the lack of reliable predictive preclinical cancer models is a fundamental one. For decades, immortalized cancer cell cultures have been used to lay the groundwork for cancer biology and the quest for therapeutic responses. However, cell lines do not usually recapitulate cancer heterogeneity or reveal therapeutic resistance cues. With the rapidly evolving exploration of cancer “omics,” the scientific community is increasingly investigating whether the employment of short-term patient-derived tumor cell cultures (two- and three-dimensional and/or patient-derived xenograft models might provide a more representative delineation of the cancer core and its therapeutic response. Patient-derived cancer models allow the integration of genomic with drug sensitivity data on a personalized basis and currently represent the ultimate approach for preclinical drug development and biomarker discovery. The proper use of these patient-derived cancer models might soon influence clinical outcomes and allow the implementation of tailored personalized therapy. When assessing drug efficacy for the treatment of glioblastoma multiforme (GBM, currently, the most reliable models are generated through direct injection of patient-derived cells or more frequently the isolation of glioblastoma cells endowed with stem-like features and orthotopically injecting these cells into the cerebrum of immunodeficient mice. Herein, we present the key strengths, weaknesses, and potential applications of cell- and animal-based models of GBM, highlighting our experience with the glioblastoma stem-like patient cell-derived xenograft model and its utility in drug discovery.

  20. Primary prevention of colorectal cancer.

    Science.gov (United States)

    Chan, Andrew T; Giovannucci, Edward L

    2010-06-01

    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 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 maintenance of a reasonable level of physical activity are associated with markedly lower risks of colorectal cancer. Medications such as aspirin and nonsteroidal anti-inflammatory drugs and postmenopausal hormones for women are associated with substantial 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.

  1. Social media in colorectal surgery.

    Science.gov (United States)

    Wexner, S D; Petrucci, A M; Brady, R R; Ennis-O'Connor, M; Fitzgerald, J E; Mayol, J

    2017-02-01

    The engagement of social media in healthcare continues to expand. For members of the colorectal community, social media has already made a significant impact on practice, education and patient care. The applications are unique such that they provide a platform for instant communication and information sharing with other users worldwide. The purpose of this article is to provide an overview of how social media has the potential to change clinical practice, training, research and patient care in colorectal surgery. Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.

  2. Reporting colorectal cancer.

    Science.gov (United States)

    Quirke, P; Morris, E

    2007-01-01

    The management of colorectal cancer is a team process. High-quality reporting of colorectal cancer is very important as the whole team relies upon the skill of the pathologist. Failure to report key features can lead to undertreatment of this disease. The use of a proforma has been demonstrated to be beneficial and we recommend staying with TNM5 due to scientific and reproducibility issues with TNM6. Important features in stage II/Dukes' B cases are extramural vascular invasion, peritoneal involvement, extent of extramural spread, incomplete resection and perforation. All of these may lead to adjuvant therapy being administered. The surgically created circumferential resection margin (CRM) and the mode of its creation are important features and the CRM retains its value after preoperative therapy. Regression grading should be applied only to fully resected tumours and the dissection and sampling must be standardized to allow comparison of results between trials and centres. When reporting local resections of early-stage cancers we need to look for features that predict spread to local lymph nodes to allow a full resection to be considered.

  3. Effect of total lymphoid irradiation on pancreatic islet xenograft survival in rats

    International Nuclear Information System (INIS)

    Nakajima, Y.; Lie, T.S.; Nakauo, H.; Nakagawa, K.; Segawa, M.

    1984-01-01

    Before transplantation of Syrian hamster pancreatic islet xenografts to diabetic rats the recipients received total lymphatic system irradiation and cyclosporin A treatment after transplantation for immunosuppression. The xenograft survival times were measured and the rat anti-hamster lymphocytotoxic titers were determined by 51 Cr release assay

  4. Effect of total lymphoid irradiation on pancreatic islet xenograft survival in rats

    Energy Technology Data Exchange (ETDEWEB)

    Nakajima, Y; Lie, T S [Bonn Univ. (Germany, F.R.). Chirurgische Klinik und Poliklinik; Nakauo, H; Nakagawa, K; Segawa, M [Nara Women' s Univ. (Japan). Dept. of Physics

    1984-01-01

    Before transplantation of Syrian hamster pancreatic islet xenografts to diabetic rats the recipients received total lymphatic system irradiation and cyclosporin A treatment after transplantation for immunosuppression. The xenograft survival times were measured and the rat anti-hamster lymphocytotoxic titers were determined by /sup 51/Cr release assay.

  5. Dynamic modulation of phosphoprotein expression in ovarian cancer xenograft models

    International Nuclear Information System (INIS)

    Koussounadis, Antonis; Langdon, Simon P.; Um, Inhwa; Kay, Charlene; Francis, Kyle E.; Harrison, David J.; Smith, V. Anne

    2016-01-01

    The dynamic changes that occur in protein expression after treatment of a cancer in vivo are poorly described. In this study we measure the effect of chemotherapy over time on the expression of a panel of proteins in ovarian cancer xenograft models. The objective was to identify phosphoprotein and other protein changes indicative of pathway activation that might link with drug response. Two xenograft models, platinum-responsive OV1002 and platinum-unresponsive HOX424, were used. Treatments were carboplatin and carboplatin-paclitaxel. Expression of 49 proteins over 14 days post treatment was measured by quantitative immunofluorescence and analysed by AQUA. Carboplatin treatment in the platinum-sensitive OV1002 model triggered up-regulation of cell cycle, mTOR and DDR pathways, while at late time points WNT, invasion, EMT and MAPK pathways were modulated. Estrogen receptor-alpha (ESR1) and ERBB pathways were down-regulated early, within 24 h from treatment administration. Combined carboplatin-paclitaxel treatment triggered a more extensive response in the OV1002 model modulating expression of 23 of 49 proteins. Therefore the cell cycle and DDR pathways showed similar or more pronounced changes than with carboplatin alone. In addition to expression of pS6 and pERK increasing, components of the AKT pathway were modulated with pAKT increasing while its regulator PTEN was down-regulated early. WNT signaling, EMT and invasion markers were modulated at later time points. Additional pathways were also observed with the NFκB and JAK/STAT pathways being up-regulated. ESR1 was down-regulated as was HER4, while further protein members of the ERBB pathway were upregulated late. By contrast, in the carboplatin-unresponsive HOX 424 xenograft, carboplatin only modulated expression of MLH1 while carboplatin-paclitaxel treatment modulated ESR1 and pMET. Thirteen proteins were modulated by carboplatin and a more robust set of changes by carboplatin-paclitaxel. Early changes included

  6. Anti-tumor effects of ONC201 in combination with VEGF-inhibitors significantly impacts colorectal cancer growth and survival in vivo through complementary non-overlapping mechanisms.

    Science.gov (United States)

    Wagner, Jessica; Kline, C Leah; Zhou, Lanlan; Khazak, Vladimir; El-Deiry, Wafik S

    2018-01-22

    Small molecule ONC201 is an investigational anti-tumor agent that upregulates intra-tumoral TRAIL expression and the integrated stress response pathway. A Phase I clinical trial using ONC201 therapy in advanced cancer patients has been completed and the drug has progressed into Phase II trials in several cancer types. Colorectal cancer (CRC) remains one of the leading causes of cancer worldwide and metastatic disease has a poor prognosis. Clinical trials in CRC and other tumor types have demonstrated that therapeutics targeting the vascular endothelial growth factor (VEGF) pathway, such as bevacizumab, are effective in combination with certain chemotherapeutic agents. We investigated the potential combination of VEGF inhibitors such as bevacizumab and its murine-counterpart; along with other anti-angiogenic agents and ONC201 in both CRC xenograft and patient-derived xenograft (PDX) models. We utilized non-invasive imaging and immunohistochemistry to determine potential mechanisms of action. Our results demonstrate significant tumor regression or complete tumor ablation in human xenografts with the combination of ONC201 with bevacizumab, and in syngeneic MC38 colorectal cancer xenografts using a murine VEGF-A inhibitor. Imaging demonstrated the impact of this combination on decreasing tumor growth and tumor metastasis. Our results indicate that ONC201 and anti-angiogenic agents act through distinct mechanisms while increasing tumor cell death and inhibiting proliferation. With the use of both a murine VEGF inhibitor in syngeneic models, and bevacizumab in human cell line-derived xenografts, we demonstrate that ONC201 in combination with anti-angiogenic therapies such as bevacizumab represents a promising approach for further testing in the clinic for the treatment of CRC.

  7. Human airway xenograft models of epithelial cell regeneration

    Directory of Open Access Journals (Sweden)

    Puchelle Edith

    2000-10-01

    Full Text Available Abstract Regeneration and restoration of the airway epithelium after mechanical, viral or bacterial injury have a determinant role in the evolution of numerous respiratory diseases such as chronic bronchitis, asthma and cystic fibrosis. The study in vivo of epithelial regeneration in animal models has shown that airway epithelial cells are able to dedifferentiate, spread, migrate over the denuded basement membrane and progressively redifferentiate to restore a functional respiratory epithelium after several weeks. Recently, human tracheal xenografts have been developed in immunodeficient severe combined immunodeficiency (SCID and nude mice. In this review we recall that human airway cells implanted in such conditioned host grafts can regenerate a well-differentiated and functional human epithelium; we stress the interest in these humanized mice in assaying candidate progenitor and stem cells of the human airway mucosa.

  8. The influence of royal jelly and human interferon-alpha (HuIFN-αN3) on proliferation, glutathione level and lipid peroxidation in human colorectal adenocarcinoma cells in vitro.

    Science.gov (United States)

    Filipič, Bratko; Gradišnik, Lidija; Rihar, Klemen; Šooš, Eugen; Pereyra, Adriana; Potokar, Jana

    2015-12-01

    Among royal jelly's (RJ) various biological activities, its possible antitumour activity deserves particular attention. The purpose of this study was to investigate the influence of RJ, its bioactive component 10-hydroxy-2-decenoic acid (10- HDA), and human interferon-alpha (HuIFN-αN3) on the proliferation of human colorectal adenocarcinoma cells (CaCo- 2), and ascertain their effect on intracellular glutathione (GSH) level and lipid peroxidation. We studied the antiproliferative (AP) activity of RJ [(0.1 g/10 mL phosphate buffer saline (PBS)], HuIFN-αN3 (1000 I.U. mL⁻¹), 10-HDA at 100.0 μmol L⁻¹, and their different combinations, in the ratio 1:1, 1:2, and 2:1 on CaCo-2 cells. The GSH level was measured by glutathione assay. The lipid peroxidation was measured by malondialdehyde (MDA) assay. Single RJ had a low AP activity: 2.0 (0.5 mg mL⁻¹). HuIFN-αN3 had an AP activity of 2.5 (208.33 I.U. mL⁻¹), while 10-HDA had an AP activity of 1.5 (37.5 μmol mL⁻¹). The highest AP activity of 3.8 was obtained when RJ and HuIFN-αN3 were applied at the ratio 2:1. In that combination the level of GSH was 24.9±2.4 nmol g⁻³ of proteins (vs. 70.2±3.2 nmol g⁻³ in the control) and the level of MDA was 72.3±3.1 nmol g⁻³ (vs. 23.6±9.1 nmol g⁻³ in the control). It is generally assumed that 10-HDA, an important constituent of RJ, together with HuIFN-αN3, is responsible for the inhibition of CaCo-2 cells proliferation in vitro. In our study, however, RJ and HuIFN-αN3 applied at 2:1 decreased the level of GSH the most and significantly increased lipid peroxidation via MDA in CaCo-2 cells. Future studies should show whether these GSH- and MDA-related activities of RJ, HuIFN-αN3, 10-HDA, and their combinations may decrease the tumorigenicity index and tumorigenic potential of various tumour cells in vitro.

  9. Dietary patterns and colorectal adenomas in Lynch syndrome: the GEOLynch cohort study.

    Science.gov (United States)

    Botma, Akke; Vasen, Hans F A; van Duijnhoven, Fränzel J B; Kleibeuker, Jan H; Nagengast, Fokko M; Kampman, Ellen

    2013-02-01

    Patients with Lynch syndrome (LS) have a high risk of developing colorectal cancer due to mutations in mismatch repair genes. Because dietary factors, alone and in combination, influence sporadic colorectal carcinogenesis, the association of dietary patterns with colorectal adenomas in LS patients was assessed. In the GEOLynch cohort of 486 persons with LS, dietary information was collected, using a food frequency questionnaire. Dietary pattern scores were obtained by principal components analysis. Hazard ratios (HR) between dietary patterns and colorectal adenomas were calculated using Cox regression models. Robust sandwich variance estimates were used to control for dependency within families. Final models were adjusted for age, sex, smoking habits, colorectal adenoma history, and extent of colon resection. During a median follow-up of 20 months, colorectal adenomas were detected in 58 persons. Four dietary patterns were identified: a "Prudent," "Meat," "Snack," and "Cosmopolitan" pattern. Individuals within the highest tertile of the "Prudent" pattern had a HR of 0.73 (95% confidence interval [CI], 0.32-1.66) for colorectal adenomas, compared with the lowest tertile. Those with high "Meat" pattern scores had a HR of 1.70 (95% CI, 0.83-3.52). A high "Snack" pattern was associated with an increased risk of colorectal adenomas (HR, 2.16; 95% CI, 1.03-4.49). A HR of 1.25 (95% CI, 0.61-2.55) was observed for persons in the highest tertile of the "Cosmopolitan" pattern. These findings suggest that dietary patterns may be associated with development of colorectal adenoma in patients with Lynch syndrome. The directions of these findings are corroborative with those observed in studies investigating sporadic colorectal cancer. Copyright © 2012 American Cancer Society.

  10. Diagnostic Ultrasound in Colorectal Cancer

    DEFF Research Database (Denmark)

    Rafaelsen, Søren Rafael

    2014-01-01

    SUMMARYBackground and purpose Colorectal cancer is a common disease in Denmark with considerable morbidity and mortality. Although survival in recent years has improved, Denmark still has the lowest 5-year survival compared to the other Nordic countries. The treatment of patients depends on local...... 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...... of 295 patients with primary colorectal cancer we found a sensitivity of preoperative ultrasound, surgical exploration, and intraoperative ultrasound of 70%, 84%, and 97%, respectively, based on a patient-by-patient comparison (p

  11. 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...

  12. Colorectal Anastomotic Leakage: New perspectives

    NARCIS (Netherlands)

    F. Daams (Freek)

    2014-01-01

    markdownabstract__Abstract__ This thesis provides new perspectives on colorectal anastomotic leakages. In both experimental and clinical studies, aspects of prevention, early identification, treatment and consequences of anastomotic leakage are discussed.

  13. Obesity and colorectal cancer risk

    International Nuclear Information System (INIS)

    Hano Garcia, Olga Marina; Wood Rodriguez, Lisette; Villa Jimenez, Oscar Manuel

    2011-01-01

    Obesity is a chronic and multifactor disease characterized by presence of excess body fat harmful for health. Several studies have been conducted to assess the possible risk character of different factors for colorectal cancer including the following modifying factors: a diet rich in saturated fats, a diet low in vegetables, physical inactivity, alcohol consumption and obesity. A case-control study was conducted to include 276 adult patients (93 cases and 184 controls) consecutively seen from May, 2008 to May, 2009 in the Institute of Gastroenterology determining a possible association between obesity as risk factor and colorectal cancer. Variables measures included: sex, age, skin color, body mass index, hip-waist circumference and endoscopic location of cancer. We conclude that the colorectal cancer with predominance in female sex and in white people in both groups. Obesity according to a great relation hip-waist had an strong relation with colorectal cancer, which had predominance towards distal colon in both sexes

  14. 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....

  15. 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, histopathologic...... 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....

  16. EPIDEMIOLOGICAL EVALUATION OF COLORECTAL CANCER

    OpenAIRE

    B. Shafayan M. Keyhani

    2003-01-01

    This study was carried out to analyze certain epidemiological variations in Iranian patients with colorectal cancer. (CRC): From March 1981 up to March 1993, 103 patients were analyzed retrospectively for age, gender, marital state, job, nutritional habits, presenting symptoms and histopathological features. Most of the patients with colorectal cancer were male, age range 20-75 (mean 56), 25.4 percent were long-term smokers and bleeding was the most common symptom. The rectum was the most com...

  17. Australian contemporary management of synchronous metastatic colorectal cancer.

    Science.gov (United States)

    Malouf, Phillip; Gibbs, Peter; Shapiro, Jeremy; Sockler, Jim; Bell, Stephen

    2018-01-01

    This article outlines the current Australian multidisciplinary treatment of synchronous metastatic colorectal adenocarcinoma and assesses the factors that influence patient outcome. This is a retrospective analysis of the prospective 'Treatment of Recurrent and Advanced Colorectal Cancer' registry, describing the patient treatment pathway and documenting the extent of disease, resection of the colorectal primary and metastases, chemotherapy and biological therapy use. Cox regression models for progression-free and overall survival were constructed with a comprehensive set of clinical variables. Analysis was intentionn-ton-treat, quantifying the effect of treatment intent decided at the multidisciplinary team meeting (MDT). One thousand one hundred and nine patients presented with synchronous metastatic disease between July 2009 and November 2015. Median follow-up was 15.8 months; 4.4% (group 1) had already curative resections of primary and metastases prior to MDT, 22.2% (group 2) were considered curative but were referred to MDT for opinion and/or medical oncology treatment prior to resection and 70.2% were considered palliative at MDT (group 3). Overall, 83% received chemotherapy, 55% had their primary resected and 23% had their metastases resected; 13% of resections were synchronous, 20% were staged with primary resected first and 62% had only the colorectal primary managed surgically. Performance status, metastasis resection (R0 versus R1 versus R2 versus no resection), resection of the colorectal primary and treatment intent determined at MDT were the most significant factors for progression-free and overall survival. This is the largest Australian series of synchronous metastatic colorectal adenocarcinoma and offers insight into the nature and utility of contemporary practice. © 2016 Royal Australasian College of Surgeons.

  18. Robotics in Colorectal Surgery

    Science.gov (United States)

    Weaver, Allison; Steele, Scott

    2016-01-01

    Over the past few decades, robotic surgery has developed from a futuristic dream to a real, widely used technology. Today, robotic platforms are used for a range of procedures and have added a new facet to the development and implementation of minimally invasive surgeries. The potential advantages are enormous, but the current progress is impeded by high costs and limited technology. However, recent advances in haptic feedback systems and single-port surgical techniques demonstrate a clear role for robotics and are likely to improve surgical outcomes. Although robotic surgeries have become the gold standard for a number of procedures, the research in colorectal surgery is not definitive and more work needs to be done to prove its safety and efficacy to both surgeons and patients. PMID:27746895

  19. A blended knowledge translation initiative to improve colorectal cancer staging [ISRCTN56824239

    Directory of Open Access Journals (Sweden)

    Ryan David P

    2006-01-01

    Full Text Available Abstract Background A significant gap has been documented between best practice and the actual practice of surgery. Our group identified that colorectal cancer staging in Ontario was suboptimal and subsequently developed a knowledge translation strategy using the principles of social marketing and the influence of expert and local opinion leaders for colorectal cancer. Methods/Design Opinion leaders were identified using the Hiss methodology. Hospitals in Ontario were cluster-randomized to one of two intervention arms. Both groups were exposed to a formal continuing medical education session given by the expert opinion leader for colorectal cancer. In the treatment group the local Opinion Leader for colorectal cancer was detailed by the expert opinion leader for colorectal cancer and received a toolkit. Forty-two centres agreed to have the expert opinion leader for colorectal cancer come and give a formal continuing medical education session that lasted between 50 minutes and 4 hours. No centres refused the intervention. These sessions were generally well attended by most surgeons, pathologists and other health care professionals at each centre. In addition all but one of the local opinion leaders for colorectal cancer met with the expert opinion leader for colorectal cancer for the academic detailing session that lasted between 15 and 30 minutes. Discussion We have enacted a unique study that has attempted to induce practice change among surgeons and pathologists using an adapted social marketing model that utilized the influence of both expert and local opinion leaders for colorectal cancer in a large geographic area with diverse practice settings.

  20. Prospective study of dietary patterns and colorectal cancer among Singapore Chinese

    OpenAIRE

    Butler, L M; Wang, R; Koh, W-P; Yu, M C

    2008-01-01

    An influence of Western diet and lifestyle factors observed among Singapore Chinese may contribute to the population's marked rise in colorectal cancer incidence over the past two decades. Thus far, however, there is little evidence for individual nutrients and foods as major contributing factors in this population. We evaluated whether patterns of food intake were associated with colorectal cancer in a population-based cohort of 61,321 Singapore Chinese that was established in 1993?98. Two d...

  1. Hyaluronic Acid in Normal and Neoplastic Colorectal Tissue: Electrospray Ionization Mass Spectrometric and Fluor Metric Analysis

    Directory of Open Access Journals (Sweden)

    Ana Paula Cleto Marolla

    2016-01-01

    Conclusions: The expression of HA was found to be slightly lower in tumor tissue than in colorectal non-neoplastic mucosa, although this difference was not statistically significant. This finding probably influenced the lower expression of HA in tumor tissue than in colorectal non-neoplastic mucosa. Compared to normal tissues, HA levels are significantly increased in the tumor tissues unless they exhibit lymph node metastasis. Otherwise, the expression of HA in tumor tissue did not correlated with the other clinicopathological parameters.

  2. Colorectal Cancer: Prognostic Values

    Directory of Open Access Journals (Sweden)

    Suzana Manxhuka-Kerliu

    2009-02-01

    Full Text Available After lung cancer colorectal cancer (Cc is ranked the second, as a cause of cancer-related death. The purpose of this study was to analyze the Cc cases in our material with respect to all prognostic values including histological type and grade, vascular invasion, perineural invasion, and tumor border features. There were investigated 149 cases of resection specimen with colorectal cancer, which were fixed in buffered neutral formalin and embedded in paraffin. Tissue sections (4(µm thick were cut and stained with H&E. Adenocarcinoma was the most frequent histological type found in 85,90% of cases, in 60,94% of males and 39,06% of females; squamous cell carcinoma in 7,38%, in 63,63% of males and 36,36% of females; mucinous carcinoma in 4,68%, in 57,15% of males and 42,85% of females; while adenosquamous carcinoma, undifferentiated carcinoma and carcinoma in situ in 0,71% of cases each. Dukes' classification was used in order to define the depth of invasion. Dukes B was found in 68,45% of cases, whereas in 31,54% of cases Dukes C was found. As far as histological grading is concerned, Cc was mostly with moderate differentiation (75,16% with neither vascular nor perineural invasion. Resection margins were in all cases free of tumor. Our data indicate that the pathologic features of the resection specimen constitute the most powerful predictors of postoperative outcome in Cc. Dukes' stage and degree of differentiation provide independent prognostic information in Cc. However, differentiation should be assessed by the worst pattern.

  3. Long-term results after aortic valve replacement with the Biocor PSB stentless xenograft in the elderly.

    Science.gov (United States)

    Luciani, G B; Santini, F; Auriemma, S; Barozzi, L; Bertolini, P; Mazzucco, A

    2001-05-01

    This study seeks to define the long-term results after Biocor PSB stentless aortic valve replacement (AVR) in elderly patients, including the effects of No-React treatment. We reviewed the outcomes of 106 consecutive patients, aged 70+/-6 years, having Biocor PSB (93 standard, 13 No-React) AVR between October 1992 and October 1996. There were three early deaths (3%) and 15 late deaths (15%), during a mean follow-up of 5.8+/-1.6 years. At 8 years, survival was 82%+/-4% and freedom from cardiac death was 94%+/-3%. Freedom from valve failure was 92%+/-4% at 8 years (No-React: 92%+/-8% at 4 years). Replacement of the xenograft was required in 5 patients. Freedom from reoperation was 91%+/-4% at 8 years (No-React: 92%+/-8% at 4 years). Four bleeding and two embolic events were recorded: overall valve-related event-free survival was 81%+/-7% at 8 years (No-React: 76%+/-12% at 4 years). Age of long-term survivors averaged 77+/-5 years and their New York Heart Association status was 1.3+/-0.6 (versus 2.9+/-0.6 preoperatively, p = 0.01). Satisfactory freedom from cardiac events and from valve deterioration added to uniform improvement in functional status despite advanced age and high prevalence of comorbid conditions make AVR with the Biocor PSB xenograft a valid long-term therapy for the elderly. No-React treatment does not influence xenograft durability.

  4. Gut microbiota modulate T cell trafficking into human colorectal cancer.

    Science.gov (United States)

    Cremonesi, Eleonora; Governa, Valeria; Garzon, Jesus Francisco Glaus; Mele, Valentina; Amicarella, Francesca; Muraro, Manuele Giuseppe; Trella, Emanuele; Galati-Fournier, Virginie; Oertli, Daniel; Däster, Silvio Raffael; Droeser, Raoul A; Weixler, Benjamin; Bolli, Martin; Rosso, Raffaele; Nitsche, Ulrich; Khanna, Nina; Egli, Adrian; Keck, Simone; Slotta-Huspenina, Julia; Terracciano, Luigi M; Zajac, Paul; Spagnoli, Giulio Cesare; Eppenberger-Castori, Serenella; Janssen, Klaus-Peter; Borsig, Lubor; Iezzi, Giandomenica

    2018-02-06

    Tumour-infiltrating lymphocytes (TILs) favour survival in human colorectal cancer (CRC). Chemotactic factors underlying their recruitment remain undefined. We investigated chemokines attracting T cells into human CRCs, their cellular sources and microenvironmental triggers. Expression of genes encoding immune cell markers, chemokines and bacterial 16S ribosomal RNA (16SrRNA) was assessed by quantitative reverse transcription-PCR in fresh CRC samples and corresponding tumour-free tissues. Chemokine receptor expression on TILs was evaluated by flow cytometry on cell suspensions from digested tissues. Chemokine production by CRC cells was evaluated in vitro and in vivo, on generation of intraperitoneal or intracecal tumour xenografts in immune-deficient mice. T cell trafficking was assessed on adoptive transfer of human TILs into tumour-bearing mice. Gut flora composition was analysed by 16SrRNA sequencing. CRC infiltration by distinct T cell subsets was associated with defined chemokine gene signatures, including CCL5, CXCL9 and CXCL10 for cytotoxic T lymphocytes and T-helper (Th)1 cells; CCL17, CCL22 and CXCL12 for Th1 and regulatory T cells; CXCL13 for follicular Th cells; and CCL20 and CCL17 for interleukin (IL)-17-producing Th cells. These chemokines were expressed by tumour cells on exposure to gut bacteria in vitro and in vivo. Their expression was significantly higher in intracecal than in intraperitoneal xenografts and was dramatically reduced by antibiotic treatment of tumour-bearing mice. In clinical samples, abundance of defined bacteria correlated with high chemokine expression, enhanced T cell infiltration and improved survival. Gut microbiota stimulate chemokine production by CRC cells, thus favouring recruitment of beneficial T cells into tumour tissues. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  5. Silencing of RhoA and RhoC expression by RNA interference suppresses human colorectal carcinoma growth in vivo

    Directory of Open Access Journals (Sweden)

    Wang Haibo

    2010-09-01

    Full Text Available Abstract Background RhoA and RhoC have been proved to be over-expressed in many solid cancers, including colorectal cancer. The reduction of RhoA and RhoC expression by RNA interference (RNAi resulted growth inhibition of cancer cells. The present study was to evaluate the effect of silencing of RhoA and RhoC expression by RNAi on growth of human colorectal carcinoma (CRC in tumor-bearing nude mice in vivo. Methods To establish HCT116 cell transplantable model, the nude mice were subcutaneously inoculated with 1.0 × 107 HCT116 cells and kept growing till the tumor xenografts reached 5-7 mm in diameter. Then the mice were randomly assigned to three groups(seven mice in each group: (1 normal saline(NS group, (2replication-defective recombinant adenovirus carrying the negative control shRNA (Ad-HK group and (3replication-defective recombinant adenovirus carrying the 4-tandem linked RhoA and RhoC shRNAs (Ad-RhoA-RhoC group. Ad-HK (4 × 108 pfu, 30 ul/mouse, Ad-RhoA-RhoC (4 × 108 pfu, 30 ul/mouse or PBS (30 ul/mouse was injected intratumorally four times once every other day. The weight and volumes of tumor xenografts were recorded. The levels of RhoA and RhoC mRNA transcripts and proteins in tumor xenografts were detected by reverse quantitative transcription polymerase chain reaction (QRT-PCR and immunohistochemical staining respectively. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL assay was used to detect the death of cells. Results The xenografts in mice could be seen at 5th day from the implantation of HCT116 cells and all had reached 5-7 mm in size at 9th day. After injection intratumorally, the growth speed of tumor xenografts in Ad-RhoA-RhoC group was significantly delayed compared with those in NS and Ad-HK group(P RhoA and RhoC reduced more in Ad-RhoA-RhoC group than those in NS and Ad-HK group. The relative RhoA and RhoC mRNA transcripts were decreased to 48% and 43% respectively (P RhoA and Rho

  6. Reduction of NANOG Mediates the Inhibitory Effect of Aspirin on Tumor Growth and Stemness in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Hefei Wang

    2017-11-01

    Full Text Available Background/Aims: Cancer stem cells (CSCs are considered to be responsible for tumor relapse and metastasis, which serve as a potential therapeutic target for cancer. Aspirin has been shown to reduce cancer risk and mortality, particularly in colorectal cancer. However, the CSCs-suppressing effect of aspirin and its relevant mechanisms in colorectal cancer remain unclear. Methods: CCK8 assay was employed to detect the cell viability. Sphere formation assay, colony formation assay, and ALDH1 assay were performed to identify the effects of aspirin on CSC properties. Western blotting was performed to detect the expression of the stemness factors. Xenograft model was employed to identify the anti-cancer effects of aspirin in vivo. Unpaired Student t test, ANOVA test and Kruskal-Wallis test were used for the statistical comparisons. Results: Aspirin attenuated colonosphere formation and decreased the ALDH1 positive cell population of colorectal cancer cells. Aspirin inhibited xenograft tumor growth and reduced tumor cells stemness in nude mice. Consistently, aspirin decreased the protein expression of stemness-related transcription factors, including c-Myc, OCT4 and NANOG. Suppression of NANOG blocked the effect of aspirin on sphere formation. Conversely, ectopic expression of NANOG rescued the aspirin-repressed sphere formation, suggesting that NANOG is a key downstream target. Moreover, we found that aspirin repressed NANOG expression in protein level by decreasing its stability. Conclusion: We have provided new evidence that aspirin attenuates CSC properties through down-regulation of NANOG, suggesting aspirin as a promising therapeutic agent for colorectal cancer treatment.

  7. The use of lyophilised bovine bone xenograft in mandibular reconstructive surgery - an animal experimental surgery

    International Nuclear Information System (INIS)

    Samsudin, A.R.; Meor Kamal, M. Z.; Afifi Abu Bakar

    1999-01-01

    The aim of this study is to look at the effectiveness of using lyophillised bovine bone xenograft in mandibular reconstructive surgery. Six adult merino sheep underwent bilateral marginal block resection of the mandible under general anaesthesia. The defect on the right body of mandible was left alone while the similar mandibulectomy defect on the left body of mandible was reconstructed using a cortico-cancellous block of radiosterilised lyophillised bovine bone xenograft which was procured from a calve femur. The bone xenograft was fixed and immobilized using titanium mini plates and screws. All the sheep returned to the controlled grazing ground on the 7th. Postoperative day. One sheep was sacrificed every month and the mandible was retrieved for postmortem gross and microscopical histological examination. Clinical results showed no evidence of tissue rejection in the mandible of the sheep and all the wounds healed well. All sheep showed no problem with normal eating habits. Histological examination showed resorption of the xenograft very early at one month postoperative and xenograft resorption together with new host bone deposition started at 2 months postoperative and maximise at 6 months postoperative. There is also evidence showing that the cancellous portion resorp more than the cortical portion of the xenograft. In conclusion, cortico-cancellous blocks of bovine bone xenograft may be use in mandibular reconstructive surgery giving esthetically acceptable, functional, biocompatible and overall clinically predictable results

  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. Genetic Testing for Hereditary Colorectal Cancer

    Science.gov (United States)

    ... before 50). Dave has Lynch syndrome and had colorectal cancer at 28. Amy found out she has Lynch syndrome when she was diagnosed with colorectal cancer days after turning 47. Why is it Important ...

  10. Colorectal Cancer—Health Professional Version

    Science.gov (United States)

    Colorectal cancer studies often consider colon and rectal cancer together. Worldwide, colorectal cancer is the third most common form of cancer. Find evidence-based information on colon and rectal cancer treatment, causes and prevention, screening, research, genetics, and statistics.

  11. Colorectal Cancer: What You Should Know

    Science.gov (United States)

    ... Products For Consumers Home For Consumers Consumer Updates Colorectal Cancer: What You Should Know Share Tweet Linkedin Pin ... with—and more than 50,000 died from—colorectal cancer, according to the National Cancer Institute. It is ...

  12. Sarcopenia is associated with an increased risk of advanced colorectal neoplasia.

    Science.gov (United States)

    Park, Youn Su; Kim, Ji Won; Kim, Byeong Gwan; Lee, Kook Lae; Lee, Jae Kyung; Kim, Joo Sung; Koh, Seong-Joon

    2017-04-01

    Although sarcopenia is associated with an increased risk for mortality after the curative resection of colorectal cancer, its influence on the development of advanced colonic neoplasia remains unclear. This study included 1270 subjects aged 40 years or older evaluated with first-time screening colonoscopy at Seoul National University Boramae Health Care Center from January 2010 to February 2015. Skeletal muscle mass was measured with a body composition analyzer (direct segmental multifrequency bioelectrical impedance analysis method). Multiple logistic regression analysis was performed to determine whether sarcopenia is associated with advanced colorectal neoplasia. Of 1270 subjects, 139 (10.9%) were categorized into the sarcopenia group and 1131 (89.1%) into the non-sarcopenia group. In the non-sarcopenia group, 55 subjects (4.9%) had advanced colorectal neoplasia. However, in the sarcopenia group, 19 subjects (13.7%) had advanced colorectal neoplasia, including 1 subject with invasive colorectal cancer (0.7%). In addition, subjects with sarcopenia had a higher prevalence of advanced adenoma (P sarcopenia. According to the multiple logistic regression analysis adjusted for variable confounders, age (odds ratio 1.062, 95% confidence interval 1.032-1.093; P sarcopenia (odds ratio 2.347, 95% confidence interval 1.311-4.202; P = 0.004) were associated with an advanced colorectal neoplasia. Sarcopenia is associated with an increased risk of advanced colorectal neoplasia.

  13. 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

  14. Colorectal cancer with venous tumor thrombosis

    OpenAIRE

    Kensuke Otani; Soichiro Ishihara; Keisuke Hata; Koji Murono; Kazuhito Sasaki; Koji Yasuda; Takeshi Nishikawa; Toshiaki Tanaka; Tomomichi Kiyomatsu; Kazushige Kawai; Hiroaki Nozawa; Hironori Yamaguchi; Toshiaki Watanabe

    2018-01-01

    Summary: Colorectal cancer is seldom accompanied by venous tumor thrombosis, and little is known about the features of venous tumor thrombosis in colorectal cancer. However, some reports show that colorectal cancer patients can develop venous tumor thrombosis and warn clinicians not to overlook this complication. In this report, we perform a review of 43 previously reported cases and investigate the characteristics of colorectal cancer accompanied by venous tumor thrombosis. The histological ...

  15. Colorectal cancer complicating Crohn's disease.

    Science.gov (United States)

    Freeman, H J

    2001-04-01

    Some earlier studies have indicated that patients with inflammatory bowel disease, especially those with long-standing and extensive ulcerative colitis, have an increased risk of colorectal cancer. Moreover, others in tertiary care centres have suggested that patients with Crohn's disease also have a higher risk of colorectal cancer. Canadian data on colorectal cancer in Crohn's disease appear to be limited. For this investigation, a single clinician database of 877 patients with Crohn's disease was used. Altogether, there were six patients with colorectal cancer (ie, overall rate of 0.7%). All of these patients were men with an initial diagnosis of Crohn's disease established at a mean age of approximately 28 years, with either ileocolonic disease or colonic disease alone, but not with ileal disease alone. Although there was a predominance of women in the overall study population (ie, 56.1%), no women developed colorectal cancer. The clinical behaviour of Crohn's disease was classified as nonstricturing in all six patients with colorectal cancer, but in two patients, Crohn's disease was complicated by a perirectal abscess or a fistula. All cancers were located in the rectum and were diagnosed 30 years, 22 years, seven years, 18 years, 20 years and 40 years after Crohn's disease was initially diagnosed. In three patients, the cancer was detected in a residual rectal stump after a partial colon resection at least 10 years earlier. In five patients, localized extension of disease through the serosa, nodal or distant metastases (ie, liver, lung) was found at the time of cancer diagnosis; two patients have since died. The present study confirms that Crohn's disease involving the colon may be a possible risk factor for the development of colorectal cancer, at least in younger men, but, in this study, not in women. However, part of this increased risk in men may have been related to the presence of a rectal stump, rather than to Crohn's disease per se.

  16. Colorectal Cancer Complicating Crohn's Disease

    Directory of Open Access Journals (Sweden)

    Hugh J Freeman

    2001-01-01

    Full Text Available Some earlier studies have indicated that patients with inflammatory bowel disease, especially those with long-standing and extensive ulcerative colitis, have an increased risk of colorectal cancer. Moreover, others in tertiary care centres have suggested that patients with Crohn's disease also have a higher risk of colorectal cancer. Canadian data on colorectal cancer in Crohn's disease appear to be limited. For this investigation, a single clinician database of 877 patients with Crohn's disease was used. Altogether, there were six patients with colorectal cancer (ie, overall rate of 0.7%. All of these patients were men with an initial diagnosis of Crohn's disease established at a mean age of approximately 28 years, with either ileocolonic disease or colonic disease alone, but not with ileal disease alone. Although there was a predominance of women in the overall study population (ie, 56.1%, no women developed colorectal cancer. The clinical behaviour of Crohn's disease was classified as nonstricturing in all six patients with colorectal cancer, but in two patients, Crohn's disease was complicated by a perirectal abscess or a fistula. All cancers were located in the rectum and were diagnosed 30 years, 22 years, seven years, 18 years, 20 years and 40 years after Crohn's disease was initially diagnosed. In three patients, the cancer was detected in a residual rectal stump after a partial colon resection at least 10 years earlier. In five patients, localized extension of disease through the serosa, nodal or distant metastases (ie, liver, lung was found at the time of cancer diagnosis; two patients have since died. The present study confirms that Crohn's disease involving the colon may be a possible risk factor for the development of colorectal cancer, at least in younger men, but, in this study, not in women. However, part of this increased risk in men may have been related to the presence of a rectal stump, rather than to Crohn's disease per se.

  17. Ezrin/NF-kB activation regulates epithelial- mesenchymal transition induced by EGF and promotes metastasis of colorectal cancer.

    Science.gov (United States)

    Li, Yingru; Lin, Zhaoyu; Chen, Bin; Chen, Shuang; Jiang, Zhipeng; Zhou, Taicheng; Hou, Zehui; Wang, Youyuan

    2017-08-01

    There is growing evidence that epithelial mesenchymal-transition (EMT) plays significant roles in terms of tumor metastasis. There are a lot of cytokines inducing EMT of tumor cells, EGF is one of the important cytokines.Ezrin is a connexin between the cytoskeleton and the cell membrane, which is closely related to the morphological movement and metastasis of tumor cells.EGF can activate Ezrin and affects cell motility. In recent years, many studies have shown that NF-kB acts as an important transcription factor, involving in the process of EMT. However, does Ezrin participate in the regulation of EGF-induced EMT through the NF-kB pathway? This question needs us to discuss.In the present study, we found that EGF could induce colorectal cancer cells to develop EMT,enhance their ability to invade and migrate and promotes phosphorylation of Ezrin Tyr353.On the other hand, inhibition of Ezrin could reverse EGF-induced EMT and inhibit NF-kB P65 translocating into the nucleus. Finally, knockout of Ezrin inhibited EGF-induced lung metastasis of colorectal cancer xenografts and abnormal activation of Ezrin and NF-kB were related with colorectal cancer metastasis and poor prognosis. Our present results suggest that Ezrin/NF-kB pathway may provide experimental evidence for new targeted drugs for colorectal cancer metastasis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  18. Risk of colorectal adenomas in relation to meat consumption, meat preparation, and genetic susceptibility in a Dutch population

    NARCIS (Netherlands)

    Tiemersma, E.W.; Voskuil, D.W.; Bunschoten, A.; Kok, F.J.; Kampman, E.

    2004-01-01

    Objective: We studied the association between meat consumption and colorectal adenomas, and potential influence of genetic susceptibility to heterocyclic aromatic amines (HCAs) formed during meat cooking at high temperatures. Methods: We studied HCA concentration in relation to preparation habits

  19. Genetic variants of methyl metabolizing enzymes and epigenetic regulators: Associations with promoter CpG island hypermethylation in colorectal cancer

    NARCIS (Netherlands)

    Vogel, S. de; Wouters, K.A.D.; Gottschalk, R.W.H.; Schooten, F.J. van; Goeij, A.F.P.M. de; Bruïne, A.P. de; Goldbohm, R.A.; Brandt, P.A. van den; Weijenberg, M.P.; Engeland, M. van

    2009-01-01

    Aberrant DNA methylation affects carcinogenesis of colorectal cancer. Folate metabolizing enzymes may influence the bioavailability of methyl groups, whereas DNA and histone methyltransferases are involved in epigenetic regulation of gene expression. We studied associations of genetic variants of

  20. Increase in the fraction of necrotic, not apoptotic, cells in SiHa xenograft tumours shortly after irradiation

    International Nuclear Information System (INIS)

    Olive, P.L.; Vikse, C.M.; Vanderbyl, S.

    1999-01-01

    Background and purpose: Approximately 18% of the cells recovered by rapid mechanical dissociation of SiHa xenograft tumours contain large numbers of DNA strand breaks. The number of damaged cells increases to 30-40% 4-6 h after exposure to 5 or 15 Gy, returning to normal levels by 12 h. This observation is reminiscent of the rate of production of apoptotic cells in other murine and human xenograft tumours. The nature of this damage, rate of development and relation to cell proliferation rate were therefore examined in detail.Materials and methods: SiHa human cervical carcinoma cells were grown as xenograft tumours in SCID mice. Single-cell suspensions were prepared as a function of time after irradiation of the mouse and examined for DNA damage using the alkaline comet assay. Cell cycle progression was measured by flow cytometry evaluation of anti-bromodeoxyuridine-labelled tumour cells.Results: Significant numbers of apoptotic cells could not be detected in irradiated SiHa tumours using an end-labelling assay, electron microscopy, or histological examination of thin sections. Instead, xenograft cells exhibiting extensive DNA damage in the comet assay were predominantly necrotic cells. The increase in the proportion of heavily damaged cells 4-6 h after irradiation could be the result of an interplay between several factors including loss of viable cells and change in production or loss of necrotic cells. Analysis of the progression of BrdUrd-labelled cells confirmed that while 35% of cells from untreated SiHa tumours had divided and entered G 1 phase by 6 h after BrdUrd injection, none of the labelled cells from tumours exposed to 5 or 15 Gy had progressed to G 1 .Conclusions: The increase in the percentage of SiHa tumour cells with extensive DNA damage 4-6 h after irradiation is attributable to necrosis, not apoptosis. Cell cycle progression and cell loss are likely to influence the kinetics of appearance of both apoptotic and necrotic cells in irradiated tumours

  1. A human lung xenograft mouse model of Nipah virus infection.

    Directory of Open Access Journals (Sweden)

    Gustavo Valbuena

    2014-04-01

    Full Text Available Nipah virus (NiV is a member of the genus Henipavirus (family Paramyxoviridae that causes severe and often lethal respiratory illness and encephalitis in humans with high mortality rates (up to 92%. NiV can cause Acute Lung Injury (ALI in humans, and human-to-human transmission has been observed in recent outbreaks of NiV. While the exact route of transmission to humans is not known, we have previously shown that NiV can efficiently infect human respiratory epithelial cells. The molecular mechanisms of NiV-associated ALI in the human respiratory tract are unknown. Thus, there is an urgent need for models of henipavirus infection of the human respiratory tract to study the pathogenesis and understand the host responses. Here, we describe a novel human lung xenograft model in mice to study the pathogenesis of NiV. Following transplantation, human fetal lung xenografts rapidly graft and develop mature structures of adult lungs including cartilage, vascular vessels, ciliated pseudostratified columnar epithelium, and primitive "air" spaces filled with mucus and lined by cuboidal to flat epithelium. Following infection, NiV grows to high titers (10(7 TCID50/gram lung tissue as early as 3 days post infection (pi. NiV targets both the endothelium as well as respiratory epithelium in the human lung tissues, and results in syncytia formation. NiV infection in the human lung results in the production of several cytokines and chemokines including IL-6, IP-10, eotaxin, G-CSF and GM-CSF on days 5 and 7 pi. In conclusion, this study demonstrates that NiV can replicate to high titers in a novel in vivo model of the human respiratory tract, resulting in a robust inflammatory response, which is known to be associated with ALI. This model will facilitate progress in the fundamental understanding of henipavirus pathogenesis and virus-host interactions; it will also provide biologically relevant models for other respiratory viruses.

  2. Ursodeoxycholic acid induces apoptosis in hepatocellular carcinoma xenografts in mice

    Science.gov (United States)

    Liu, Hui; Xu, Hong-Wei; Zhang, Yu-Zhen; Huang, Ya; Han, Guo-Qing; Liang, Tie-Jun; Wei, Li-Li; Qin, Cheng-Yong; Qin, Cheng-Kun

    2015-01-01

    AIM: To evaluate the efficacy of ursodeoxycholic acid (UDCA) as a chemotherapeutic agent for the treatment of hepatocellular carcinoma (HCC). METHODS: BALB/c nude mice were randomized into four groups 24 h before subcutaneous injection of hepatocarcinoma BEL7402 cells suspended in phosphate buffered saline (PBS) into the right flank. The control group (n = 10) was fed a standard diet while treatment groups (n = 10 each) were fed a standard daily diet supplemented with different concentrations of UDCA (30, 50 and 70 mg/kg per day) for 21 d. Tumor growth was measured once each week, and tumor volume (V) was calculated with the following equation: V = (L × W2) × 0.52, where L is the length and W is the width of the xenograft. After 21 d, mice were killed under ether anesthesia, and tumors were excised and weighed. Apoptosis was evaluated through detection of DNA fragmentation with gel electrophoresis and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. Western blot analysis was performed to determine the expression of apoptosis-related proteins BAX, BCL2, APAF1, cleaved caspase-9, and cleaved caspase-3. RESULTS: UDCA suppressed tumor growth relative to controls. The mean tumor volumes were the following: control, 1090 ± 89 mm3; 30 mg/kg per day, 612 ± 46 mm3; 50 mg/kg per day, 563 ± 38 mm3; and 70 mg/kg per day, 221 ± 26 mm3. Decreased tumor volumes reached statistical significance relative to control xenografts (30 mg/kg per day, P < 0.05; 50 mg/kg per day, P < 0.05; 70 mg/kg per day, P < 0.01). Increasing concentrations of UDCA led to increased DNA fragmentation observed on gel electrophoresis and in the TUNEL assay (control, 1.6% ± 0.3%; 30 mg/kg per day, 2.9% ± 0.5%; 50 mg/kg per day, 3.15% ± 0.7%, and 70 mg/kg per day, 4.86% ± 0.9%). Western blot analysis revealed increased expression of BAX, APAF1, cleaved-caspase-9 and cleaved-caspase-3 proteins, which induce apoptosis, but decreased expression of BCL2

  3. Abdominal sacrocolpopexy with Pelvicol xenograft and concomitant Burch colposuspension

    Directory of Open Access Journals (Sweden)

    Hijazi S

    2017-09-01

    Full Text Available Sameh Hijazi,1,2 Dieter Echtle,3 Omar M Aboumarzouk,4 Elmar Heinrich2,5 1Department of Urology, Klinikum Ibbenbüeren, Ibbenbüeren, 2Department of Urology, University Medical Center, Goettingen, 3Department of Urology, Städtische Kliniken Mönchengladbach, Mönchengladbach, Germany; 4Urology Department, Newport, Wales, UK; 5Department of Urology, Klinikum Wels-Grieskirchen, Standort Wels, Austria Purpose: To evaluate the efficacy of Pelvicol xenograft use during abdominal sacrocolpopexy to repair pelvic organ prolapse (POP.Patients and methods: A total of 27 consecutive women with symptomatic POP were included in this study. A POP-quantification system and International Continence Society classification were used. Functional and anatomical outcomes were assessed. Subjective outcomes and physical activity after surgery were evaluated due to modified quality of life questionnaire.Results: Median follow-up was 21 months (range: 16 to 41 months. Twenty-four (89% patients were available for anatomical and subjective evaluation. Preoperative POP- quantification classification was: stage I: 11.1%, stage II: 25.9%, stage III: 48.2%, and stage IV: 14.8%. Overall, pad usage significantly decreased (mean 4.8 vs 1 pads, P=0.001. Stress urinary incontinence significantly improved after surgery in nine women (P=0.001. An additional five women were completely continent. No de-novo incontinence developed. Six women with preoperative urinary retention improved in the amount of residual urine postoperative (mean 35 vs 165 mL. Failure rate was 8.3% at 3 and 11 months after surgery, requiring a second reconstruction. There was no graft related complications or graft rejections necessitating removal occurring. Response rate of the questionnaire was 67%. Two women reported no interference in physical activity after 2 postoperative months, five women after 5 months, and five women 1 year later. Pelvic pain (vaginal pain was partly improved in eight patients

  4. Ursodeoxycholic acid induces apoptosis in hepatocellular carcinoma xenografts in mice.

    Science.gov (United States)

    Liu, Hui; Xu, Hong-Wei; Zhang, Yu-Zhen; Huang, Ya; Han, Guo-Qing; Liang, Tie-Jun; Wei, Li-Li; Qin, Cheng-Yong; Qin, Cheng-Kun

    2015-09-28

    To evaluate the efficacy of ursodeoxycholic acid (UDCA) as a chemotherapeutic agent for the treatment of hepatocellular carcinoma (HCC). BALB/c nude mice were randomized into four groups 24 h before subcutaneous injection of hepatocarcinoma BEL7402 cells suspended in phosphate buffered saline (PBS) into the right flank. The control group (n = 10) was fed a standard diet while treatment groups (n = 10 each) were fed a standard daily diet supplemented with different concentrations of UDCA (30, 50 and 70 mg/kg per day) for 21 d. Tumor growth was measured once each week, and tumor volume (V) was calculated with the following equation: V = (L × W(2)) × 0.52, where L is the length and W is the width of the xenograft. After 21 d, mice were killed under ether anesthesia, and tumors were excised and weighed. Apoptosis was evaluated through detection of DNA fragmentation with gel electrophoresis and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. Western blot analysis was performed to determine the expression of apoptosis-related proteins BAX, BCL2, APAF1, cleaved caspase-9, and cleaved caspase-3. UDCA suppressed tumor growth relative to controls. The mean tumor volumes were the following: control, 1090 ± 89 mm(3); 30 mg/kg per day, 612 ± 46 mm(3); 50 mg/kg per day, 563 ± 38 mm(3); and 70 mg/kg per day, 221 ± 26 mm(3). Decreased tumor volumes reached statistical significance relative to control xenografts (30 mg/kg per day, P < 0.05; 50 mg/kg per day, P < 0.05; 70 mg/kg per day, P < 0.01). Increasing concentrations of UDCA led to increased DNA fragmentation observed on gel electrophoresis and in the TUNEL assay (control, 1.6% ± 0.3%; 30 mg/kg per day, 2.9% ± 0.5%; 50 mg/kg per day, 3.15% ± 0.7%, and 70 mg/kg per day, 4.86% ± 0.9%). Western blot analysis revealed increased expression of BAX, APAF1, cleaved-caspase-9 and cleaved-caspase-3 proteins, which induce apoptosis, but decreased expression of BCL2 protein, which

  5. Molecular Classification and Correlates in Colorectal Cancer

    OpenAIRE

    Ogino, Shuji; Goel, Ajay

    2008-01-01

    Molecular classification of colorectal cancer is evolving. As our understanding of colorectal carcinogenesis improves, we are incorporating new knowledge into the classification system. In particular, global genomic status [microsatellite instability (MSI) status and chromosomal instability (CIN) status] and epigenomic status [CpG island methylator phenotype (CIMP) status] play a significant role in determining clinical, pathological and biological characteristics of colorectal cancer. In thi...

  6. 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

  7. Bone morphogenetic protein signalling in colorectal cancer

    NARCIS (Netherlands)

    Hardwick, James C.; Kodach, Liudmila L.; Offerhaus, G. Johan; van den Brink, Gijs R.

    2008-01-01

    Much of the current understanding of colorectal cancer stems from the study of rare, inherited colorectal cancer syndromes. Mutations in the bone morphogenetic protein (BMP) pathway have been found in juvenile polyposis, an inherited polyposis syndrome that predisposes to colorectal cancer. The

  8. Experimental radioimmunotherapy of a xenografted human glioma using [sup 131]I-labeled monoclonal antibody to epidermal growth factor receptor

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Hiroshi; Nakazawa, Shozo [Nippon Medical School, Tokyo (Japan); Herlyn, D

    1993-09-01

    [sup 131]I-labeled F (ab')[sub 2] fragments of murine monoclonal antibodies (MAb) 425 specific to the epidermal growth factor receptor expressed on human gliomas were used in experimental human malignant glioma immunotherapy. Two injections of 150 [mu]Ci [sup 131]I-labeled 425 F(ab')[sub 2] achieved growth inhibition of U-87MG human malignant glioma xenografts in nude mice. This radiolabeled specific MAb F(ab')[sub 2] was significantly superior to radiolabeled fragments of an anti-hepatitis virus control MAb A5C3 in influencing tumor growth. However, similar treatment of established human malignant glioma xenografts did not inhibit progressive tumor growth significantly. No clear tumor inhibition was produced by unlabeled MAb 425F(ab')[sub 2]. These studies suggest that [sup 131]I-labeled MAbs have a significant antitumor effect where unmodified antibody is ineffective. Multiple doses of antibody may achieve an increase in labeled MAb concentration in tumors. (author).

  9. Brain metastasis from colorectal cancer

    International Nuclear Information System (INIS)

    Bamba, Yoshiko; Itabashi, Michio; Hirosawa, Tomoichiro; Ogawa, Shinpei; Noguchi, Eiichiro; Takemoto, Kaori; Shirotani, Noriyasu; Kameoka, Shingo

    2007-01-01

    The present study was performed to clarify the clinical characteristics of brain metastasis from colorectal cancer. Five patients with brain metastasis from colorectal cancer treated at our institute between 2001 and 2005 were included in the study. Clinical findings and survival time were determined and an appropriate system for follow-up in such cases was considered. Brain metastasis was found after surgery for colorectal cancer in 4 cases. In addition, colorectal cancer was found after diagnosis of brain metastasis in 1 case. At the time of diagnosis of brain metastasis, all patients had lung metastasis and 3 had liver metastasis. The mean periods between surgery for colorectal cancer and lung and brain metastases were 19.5 and 38.2 months, respectively. In all cases, brain metastasis was diagnosed by imaging after the appearance of neurological symptoms. Brain metastases were multiple in 1 case and focal in 4 cases. We performed gamma knife radiation therapy, and the symptoms disappeared or decreased in all cases. Mean survival time after brain metastasis was 3.0 months. Prognosis after brain metastasis is poor, but gamma knife radiation therapy contributed to patients' quality of life. (author)

  10. The role of biliverdin reductase in colorectal cancer

    International Nuclear Information System (INIS)

    Bauer, M.

    2010-01-01

    In recent years, the effects of biliverdin and bilirubin have been studied extensively, and an inhibitory effect of bile pigments in cancer progression has been proposed. In this study we focused on the effects of biliverdin reductase, the enzyme that converts biliverdin to bilirubin, in colorectal cancer. For in vitro experiments we used a human colorectal carcinoma cell line and transfected it with an expression construct of shRNA specific for biliverdin reductase, to create cells with stable knock-down of enzyme expression. Cell proliferation was analyzed using the CASY model TT cell counting device. Western blot protein analysis was performed to study intracellular signaling cascades. Samples of human colorectal cancer were analyzed using immunohistochemistry. We were able to confirm the antiproliferative effects of bile pigments on cancer cells in vitro. However, this effect was attenuated in biliverdin reductase knock down cells. ERK and Akt activation seen under biliverdin and bilirubin treatment was also reduced in biliverdin reductase deficient cells. Immunohistochemical analysis of tumor samples from patients with colorectal cancer showed elevated biliverdin reductase levels. High enzyme expression was associated with lower overall and disease free patient survival. We conclude that BVR is required for bile pigment mediated effects regarding cancer cell proliferation and modulation of intracellular signaling cascades. The role of BVR overexpression in vivo and its exact influence on cancer progression and patient survival need to be further investigated. (author) [de

  11. Curcumin-Artemisinin Coamorphous Solid: Xenograft Model Preclinical Study

    Directory of Open Access Journals (Sweden)

    M. K. Chaitanya Mannava

    2018-01-01

    Full Text Available Curcumin is a natural compound present in Indian spice turmeric. It has diverse pharmacological action but low oral solubility and bioavailability continue to limit its use as a drug. With the aim of improving the bioavailability of Curcumin (CUR, we evaluated Curcumin-Pyrogallol (CUR-PYR cocrystal and Curcumin-Artemisinin (CUR-ART coamorphous solid. Both of these solid forms exhibited superior dissolution and pharmacokinetic behavior compared to pure CUR, which is practically insoluble in water. CUR-ART coamorphous solid showed two fold higher bioavailability than CUR-PYR cocrystal (at 200 mg/kg oral dose. Moreover, in simulated gastric and intestinal fluids (SGF and SIF, CUR-ART is stable up to 3 and 12 h, respectively. In addition, CUR-PYR and CUR-ART showed no adverse effects in toxicology studies (10 times higher dose at 2000 mg/kg. CUR-ART showed higher therapeutic effect and inhibited approximately 62% of tumor growth at 100 mg/kg oral dosage of CUR in xenograft models, which is equal to the positive control drug, doxorubicin (2 mg/kg by i.v. administration.

  12. Src controls castration recurrence of CWR22 prostate cancer xenografts

    International Nuclear Information System (INIS)

    Su, Bing; Gillard, Bryan; Gao, Lingqiu; Eng, Kevin H; Gelman, Irwin H

    2013-01-01

    Recurrence of prostate cancer (CaP) after androgen-deprivation therapy continues to have the greatest impact on patient survival. Castration-recurrent (CR)-CaP is likely driven by the activation of androgen receptor (AR) through multiple mechanisms including induction of AR coregulators, AR mutants or splice variants, and AR posttranslational modification such as phosphorylation by Src-family and Ack1 tyrosine kinases. Here, we address whether Src is required for the CR growth of human CWR22 CaP xenografts. The shRNA-mediated Src knockdown or treatment with the Src inhibitors, dasatinib or KXO1, reduced CaP recurrence over controls and increased time-to-recurrence following castration. Moreover, CR-CaP [Src-shRNA] tumors that recurred had similar Src protein and activation levels as those of parental cells, strengthening the notion that Src activity is required for progression to CR-CaP. In contrast, the ability of dasatinib or KXO1 to inhibit Src kinase activity in vitro did not correlate with their ability to inhibit serum-driven in vitro proliferation of CR and androgen-dependent stable cell lines derived from CWR22 tumors (CWR22Rv1 and CWR22PC, respectively), suggesting that the in vitro proliferation of these CaP lines is Src independent. Taken together, these findings strongly suggest that Src is a potent and specific therapeutic target for CR-CaP progression

  13. Vascular abnormalities associated with acute hypoxia in human melanoma xenografts

    International Nuclear Information System (INIS)

    Simonsen, Trude G.; Gaustad, Jon-Vidar; Leinaas, Marit N.; Rofstad, Einar K.

    2012-01-01

    Background and purpose: The fraction of hypoxic cells has been shown to differ substantially among human tumors of the same histological type. In this study, a window chamber model was used to identify possible mechanisms leading to the development of highly different hypoxic fractions in A-07 and R-18 human melanoma xenografts. Materials and methods: Chronic and acute hypoxia was assessed in intradermal tumors using an immunohistochemical and a radiobiological assay. Functional and morphological parameters of the vascular networks of tumors growing in dorsal window chambers were assessed with intravital microscopy. Results: R-18 tumors showed significantly higher hypoxic fractions than A-07 tumors, and the difference was mostly due to acute hypoxia. Compared to A-07 tumors, R-18 tumors showed low vascular densities, low vessel diameters, long vessel segments, low blood flow velocities, frequent fluctuations in blood flow, and a high fraction of narrow vessels with absent or very low and varying flux of red blood cells. Conclusion: The high fraction of acute hypoxia in R-18 tumors was a consequence of frequent fluctuations in blood flow and red blood cell flux combined with low vascular density. The fluctuations were most likely caused by high geometric resistance to blood flow in the tumor microvasculature.

  14. Hypoxia and metastasis in an orthotopic cervix cancer xenograft model

    International Nuclear Information System (INIS)

    Chaudary, Naz; Mujcic, Hilda; Wouters, Bradly G.; Hill, Richard P.

    2013-01-01

    Background: Hypoxia can promote tumor metastasis by mechanisms that are believed to result from changes in gene expression. The current study examined the role of putative metastatic genes regulated by cyclic hypoxia in relation to metastasis formation in orthotopic models of cervix cancer. Methods: Orthotopic tumors derived from ME180 human cervix cancer cells or from early generation human cervix cancer xenografts were exposed to cyclic hypoxic conditions during growth in vivo and tumor growth and lymphnode metastases were monitored. Expression of the chemokine receptor CXCR4 and various genes in the Hedgehog (Hh) pathway were inhibited using genetic (inducible shRNA vs CXCR4) small molecule (AMD3100) or antibody (5E1) treatment (CXCR4 and Hh genes, respectively) during tumor growth. Results: As reported previously, exposure of tumor bearing mice to cyclic hypoxia caused a reduction of tumor growth but a large increase in metastasis. Inhibition of CXCR4 or Hh gene activity during tumor growth further reduced primary tumor size and reduced lymphatic metastasis to levels below those seen in control mice exposed to normoxic conditions. Conclusion: Blocking CXCR4 or Hh gene expression are potential therapeutic pathways for improving cervix cancer treatment

  15. Oridonin induces apoptosis and senescence in colorectal cancer cells by increasing histone hyperacetylation and regulation of p16, p21, p27 and c-myc

    International Nuclear Information System (INIS)

    Gao, Feng-Hou; Liu, Feng; Zhao, Ying-Zheng; Fang, Yong; Chen, Fang-Yuan; Wu, Ying-Li; Hu, Xiao-Hui; Li, Wei; Liu, Hua; Zhang, Yan-Jie; Guo, Zhu-Ying; Xu, Mang-Hua; Wang, Shi-Ting; Jiang, Bin

    2010-01-01

    Oridonin, a tetracycline diterpenoid compound, has the potential antitumor activities. Here, we evaluate the antitumor activity and action mechanisms of oridonin in colorectal cancer. Effects of oridonin on cell proliferation were determined by using a CCK-8 Kit. Cell cycle distribution was determined by flow cytometry. Apoptosis was examined by analyzing subdiploid population and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. Senescent cells were determined by senescence-associated β-galactosidase activity analysis. Semi-quantitative RT-PCR was used to examine the changes of mRNA of p16, p21, p27 and c-myc. The concomitant changes of protein expression were analyzed with Western blot. Expression of AcH3 and AcH4 were examined by immunofluorescence staining and Western blots. Effects of oridonin on colony formation of SW1116 were examined by Soft Agar assay. The in vivo efficacy of oridonin was detected using a xenograft colorectal cancer model in nude mice. Oridonin induced potent growth inhibition, cell cycle arrest, apoptosis, senescence and colony-forming inhibition in three colorectal cancer cell lines in a dose-dependent manner in vitro. Daily i.p. injection of oridonin (6.25, 12.5 or 25 mg/kg) for 28 days significantly inhibited the growth of SW1116 s.c. xenografts in BABL/C nude mice. With western blot and reverse transcription-PCR, we further showed that the antitumor activities of oridonin correlated with induction of histone (H3 and H4) hyperacetylation, activation of p21, p27 and p16, and suppression of c-myc expression. Oridonin possesses potent in vitro and in vivo anti-colorectal cancer activities that correlated with induction of histone hyperacetylation and regulation of pathways critical for maintaining growth inhibition and cell cycle arrest. Therefore, oridonin may represent a novel therapeutic option in colorectal cancer treatment

  16. Oridonin induces apoptosis and senescence in colorectal cancer cells by increasing histone hyperacetylation and regulation of p16, p21, p27 and c-myc

    Directory of Open Access Journals (Sweden)

    Zhao Ying-Zheng

    2010-11-01

    Full Text Available Abstract Background Oridonin, a tetracycline diterpenoid compound, has the potential antitumor activities. Here, we evaluate the antitumor activity and action mechanisms of oridonin in colorectal cancer. Methods Effects of oridonin on cell proliferation were determined by using a CCK-8 Kit. Cell cycle distribution was determined by flow cytometry. Apoptosis was examined by analyzing subdiploid population and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. Senescent cells were determined by senescence-associated β-galactosidase activity analysis. Semi-quantitative RT-PCR was used to examine the changes of mRNA of p16, p21, p27 and c-myc. The concomitant changes of protein expression were analyzed with Western blot. Expression of AcH3 and AcH4 were examined by immunofluorescence staining and Western blots. Effects of oridonin on colony formation of SW1116 were examined by Soft Agar assay. The in vivo efficacy of oridonin was detected using a xenograft colorectal cancer model in nude mice. Results Oridonin induced potent growth inhibition, cell cycle arrest, apoptosis, senescence and colony-forming inhibition in three colorectal cancer cell lines in a dose-dependent manner in vitro. Daily i.p. injection of oridonin (6.25, 12.5 or 25 mg/kg for 28 days significantly inhibited the growth of SW1116 s.c. xenografts in BABL/C nude mice. With western blot and reverse transcription-PCR, we further showed that the antitumor activities of oridonin correlated with induction of histone (H3 and H4 hyperacetylation, activation of p21, p27 and p16, and suppression of c-myc expression. Conclusion Oridonin possesses potent in vitro and in vivo anti-colorectal cancer activities that correlated with induction of histone hyperacetylation and regulation of pathways critical for maintaining growth inhibition and cell cycle arrest. Therefore, oridonin may represent a novel therapeutic option in colorectal cancer treatment.

  17. Dual-specificity tyrosine-regulated kinase 2 is a suppressor and potential prognostic marker for liver metastasis of colorectal cancer.

    Science.gov (United States)

    Ito, Daisuke; Yogosawa, Satomi; Mimoto, Rei; Hirooka, Shinichi; Horiuchi, Takashi; Eto, Ken; Yanaga, Katsuhiko; Yoshida, Kiyotsugu

    2017-08-01

    Colorectal cancer is a common cancer and a leading cause of cancer-related death worldwide. The liver is a dominant metastatic site for patients with colorectal cancer. Molecular mechanisms that allow colorectal cancer cells to form liver metastases are largely unknown. Activation of epithelial-mesenchymal transition is the key step for metastasis of cancer cells. We recently reported that dual-specificity tyrosine-regulated kinase 2 (DYRK2) controls epithelial-mesenchymal transition in breast cancer and ovarian serous adenocarcinoma. The aim of this study is to clarify whether DYRK2 regulates liver metastases of colorectal cancer. We show that the ability of cell invasion and migration was abrogated in DYRK2-overexpressing cells. In an in vivo xenograft model, liver metastatic lesions were markedly diminished by ectopic expression of DYRK2. Furthermore, we found that patients whose liver metastases expressed low DYRK2 levels had significantly worse overall and disease-free survival. Given the findings that DYRK2 regulates cancer cell metastasis, we concluded that the expression status of DYRK2 could be a predictive marker for liver metastases of colorectal cancer. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  18. Improvement of Radiation-Mediated Immunosuppression of Human NSCLC Tumour Xenografts in a Nude Rat Model

    Directory of Open Access Journals (Sweden)

    Sergey V. Tokalov

    2010-01-01

    Full Text Available Human tumour xenografts in a nude rat model have consistently been used as an essential part of preclinical studies for anticancer drugs activity in human. Commonly, these animals receive whole body irradiation to assure immunosuppression. But whole body dose delivery might be inhomogeneous and the resulting incomplete bone marrow depletion may modify tumour behaviour. To improve irradiation-mediated immunosuppression of human non-small cell lung cancer (NSCLC xenografts in a nude rat model irradiation (2 + 2 Gy from opposite sides of animals has been performed using a conventional X-ray tube. The described modification of whole body irradiation improves growth properties of human NSCLC xenografts in a nude rat model. The design of the whole body irradiation mediated immunosuppression described here for NSCLC xenografts may be useful for research applications involving other types of human tumours.

  19. Radiosensitivity and repair capacity of two xenografted human soft tissue sarcomas to photons and fast neutrons

    International Nuclear Information System (INIS)

    Budach, V.; Stuschke, M.; Budach, W.; Krause, U.; Streffer, C.; Sack, H.

    1989-01-01

    The radiation response, the relative biological effectiveness (RBE) and sublethal damage repair of two xenografted human soft tissue sarcomas after single doses and fractionated irradiation with 60 Co and 5.8 MeV fast neutrons are presented. (author)

  20. The impact of age on anxiety level and cognitive function in patients with colorectal cancer

    Directory of Open Access Journals (Sweden)

    I. S. Stilidi

    2017-01-01

    Full Text Available Background. Colorectal cancer is highly prevalent in Russia, especially among the elderly patients. We analyzed the influence of age on anxiety level and cognitive function on patients with colorectal cancer.Materials and methods. In the period 2012–2015 we analyzed pre-operatively the level of anxiety (HADS scale and cognitive disfunction (MoCA test in 244 patients who underwent radical colorectal resection.Results. Patients younger than 60 constituted 34 %, 60–74 years – 31 %, 75 years and older – 35 %. We were able to show a correlation between age and anxiety level according to HADS. The same trend was found according to MoCA test.Conclusion. Oncopsychologist shall develop individualized treatment plan according to anxiety and cognitive levels in patients with colorectal cancer.

  1. Undefined familial colorectal cancer.

    Science.gov (United States)

    Zambirinis, Constantinos Pantelis; Theodoropoulos, George; Gazouli, Maria

    2009-10-15

    Colorectal cancer (CRC), one of the most common cancers of the world, is actually a spectrum of several subtypes, with different molecular profiles, clinico-pathological characteristics and possibly separate pathways of progression. It is estimated that in approximately 25%-35% of cases, a familial component exists, so they are classified as familial CRC (fCRC). However the known hereditary CRC syndromes justify only up to 5%. The rest are attributed to some inherited genetic predisposition passed to offspring through low-penetrance genes, which in the proper environmental setting can bring on tumorigenesis. Furthermore, part of the familial clustering may be attributed to chance. Because of the complexity regarding the etiology of CRC, the clinician is sometimes faced with obscure patient data, and cannot be sure if they are dealing with fCRC or sporadic CRC. The elucidation of what is going on with the as yet "undefined" portion of CRC will aid not only in the diagnosis, classification and treatment of CRC, but more importantly in the proper adjustment of the screening guidelines and in genetic counselling of patients.

  2. Body mass index and risk of colorectal carcinoma subtypes classified by tumor differentiation status.

    Science.gov (United States)

    Hanyuda, Akiko; Cao, Yin; Hamada, Tsuyoshi; Nowak, Jonathan A; Qian, Zhi Rong; Masugi, Yohei; da Silva, Annacarolina; Liu, Li; Kosumi, Keisuke; Soong, Thing Rinda; Jhun, Iny; Wu, Kana; Zhang, Xuehong; Song, Mingyang; Meyerhardt, Jeffrey A; Chan, Andrew T; Fuchs, Charles S; Giovannucci, Edward L; Ogino, Shuji; Nishihara, Reiko

    2017-05-01

    Previous studies suggest that abnormal energy balance status may dysregulate intestinal epithelial homeostasis and promote colorectal carcinogenesis, yet little is known about how host energy balance and obesity influence enterocyte differentiation during carcinogenesis. We hypothesized that the association between high body mass index (BMI) and colorectal carcinoma incidence might differ according to tumor histopathologic differentiation status. Using databases of the Nurses' Health Study and Health Professionals Follow-up Study, and duplication-method Cox proportional hazards models, we prospectively examined an association between BMI and the incidence of colorectal carcinoma subtypes classified by differentiation features. 120,813 participants were followed for 26 or 32 years and 1528 rectal and colon cancer cases with available tumor pathological data were documented. The association between BMI and colorectal cancer risk significantly differed depending on the presence or absence of poorly-differentiated foci (P heterogeneity  = 0.006). Higher BMI was associated with a higher risk of colorectal carcinoma without poorly-differentiated foci (≥30.0 vs. 18.5-22.4 kg/m 2 : multivariable-adjusted hazard ratio, 1.87; 95% confidence interval, 1.49-2.34; P trend   0.03, with the adjusted α of 0.01). High BMI was associated with risk of colorectal cancer subtype containing no poorly-differentiated focus. Our findings suggest that carcinogenic influence of excess energy balance might be stronger for tumors that retain better intestinal differentiation throughout the tumor areas.

  3. Subnuclear proteomics in colorectal cancer

    DEFF Research Database (Denmark)

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

    2010-01-01

    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......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...... with statistics, we identified proteins that are significantly enriched in the nuclear matrix fraction relative to two earlier fractions (the chromatin-binding and intermediate filament fractions) isolated from six colorectal tissue samples. The total data set contained 2,059 non-redundant proteins. Gene ontology...

  4. EPIDEMIOLOGICAL EVALUATION OF COLORECTAL CANCER

    Directory of Open Access Journals (Sweden)

    B. Shafayan M. Keyhani

    2003-07-01

    Full Text Available This study was carried out to analyze certain epidemiological variations in Iranian patients with colorectal cancer. (CRC: From March 1981 up to March 1993, 103 patients were analyzed retrospectively for age, gender, marital state, job, nutritional habits, presenting symptoms and histopathological features. Most of the patients with colorectal cancer were male, age range 20-75 (mean 56, 25.4 percent were long-term smokers and bleeding was the most common symptom. The rectum was the most common site and moderately differentiated carcinoma was considered as the main common histopathological variety. In conclusion, increasing incidence of colorectal cancer in younger Iranian population, below 30 and late admission and diagnosis were the main findings in the present study necessitating screening programs with annual fecal occult blood tests in high risk families.

  5. Effects of histamine and 5-hydroxytryptamine on the growth rate of xenografted human bronchogenic carcinomas.

    Science.gov (United States)

    Sheehan, P F; Baker, T; Tutton, P J; Barkla, D H

    1996-01-01

    1. The influence of histamine and 5-hydroxytryptamine (5-HT) antagonists and agonists on the volume doubling times (Td) of human bronchogenic carcinomas propagated as s.c. xenografts in immunosuppressed mice was examined. 2. The H2-receptor antagonists, cimetidine and ranitidine, increased Td. 3. Treatment with the H2-receptor agonist, 4-methyl histamine, had no effect on Td. 4. Co-administration of 4-methyl histamine and cimetidine abolished the effects of cimetidine. 5. The 5-HT2-receptor antagonists, cinanserin and ketanserin, both increased Td. 6. Treatment with the 5-HT1/2-receptor agonist quipazine (0.1 mg/kg, reflecting 5-HT2 agonist activity) decreased Td, while a higher dose (10.0 mg/kg) had no effect. 7. The 5-HT1/2-receptor antagonist, methiothepin, decreased Td. 8. The 5-HT uptake inhibitor, fluoxetine, increased Td in one tumour line but not in another, while the 5-HT releaser/depletor, fenfluramine, increased Td. 9. Histamine may stimulate tumour growth through the histamine H2-receptor, while the dominant effect of 5-HT is 5-HT1-receptor inhibition. 10. Tumour growth in some bronchogenic carcinomas may involve 5-HT uptake mechanisms.

  6. Clinicopathological Analysis of Factors Related to Colorectal Tumor Perforation

    OpenAIRE

    Medina-Arana, Vicente; Martínez-Riera, Antonio; Delgado-Plasencia, Luciano; Rodríguez-González, Diana; Bravo-Gutiérrez, Alberto; Álvarez-Argüelles, Hugo; Alarcó-Hernández, Antonio; Salido-Ruiz, Eduardo; Fernández-Peralta, Antonia M.; González-Aguilera, Juan J.

    2015-01-01

    Abstract Colorectal tumor perforation is a life-threatening complication of this disease. However, little is known about the anatomopathological factors or pathophysiologic mechanisms involved. Pathological and immunohistochemical analysis of factors related with tumoral neo-angiogenesis, which could influence tumor perforation are assessed in this study. A retrospective study of patients with perforated colon tumors (Group P) and T4a nonperforated (controls) was conducted between 2001 and 20...

  7. 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

    2010-01-01

    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-1α, 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. PMID:20383296

  8. PET imaging of HER1-expressing xenografts in mice with {sup 86}Y-CHX-A''-DTPA-cetuximab

    Energy Technology Data Exchange (ETDEWEB)

    Nayak, Tapan K.; Regino, Celeste A.S.; Milenic, Diane E.; Garmestani, Kayhan; Baidoo, Kwamena E.; Brechbiel, Martin W. [National Institutes of Health, Radioimmune and Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, Bethesda, MD (United States); Wong, Karen J. [National Institutes of Health, Molecular Imaging Program, National Cancer Institute, Bethesda, MD (United States); Szajek, Lawrence P. [National Institutes of Health, PET Department, Warren G. Magnuson Clinical Center, Bethesda, MD (United States)

    2010-07-15

    Cetuximab is a recombinant, human/mouse chimeric IgG{sub 1} monoclonal antibody that binds to the epidermal growth factor receptor (EGFR/HER1). Cetuximab is approved for the treatment of patients with HER1-expressing metastatic colorectal cancer. Limitations in currently reported radiolabeled cetuximab for PET applications prompted the development of {sup 86}Y-CHX-A''-DTPA-cetuximab as an alternative for imaging HER1-expressing cancer. {sup 86}Y-CHX-A''-DTPA-cetuximab can also serve as a surrogate marker for {sup 90}Y therapy. Bifunctional chelate, CHX-A''-DTPA was conjugated to cetuximab and radiolabeled with {sup 86}Y. In vitro immunoreactivity was assessed in HER1-expressing A431 cells. In vivo biodistribution, PET imaging and noncompartmental pharmacokinetics were performed in mice bearing HER1-expressing human colorectal (LS-174T and HT29), prostate (PC-3 and DU145), ovarian (SKOV3) and pancreatic (SHAW) tumor xenografts. Receptor blockage was demonstrated by coinjection of either 0.1 or 0.2 mg cetuximab. {sup 86}Y-CHX-A''-DTPA-cetuximab was routinely prepared with a specific activity of 1.5-2 GBq/mg and in vitro cell-binding in the range 65-75%. Biodistribution and PET imaging studies demonstrated high HER1-specific tumor uptake of the radiotracer and clearance from nonspecific organs. In LS-174T tumor-bearing mice injected with {sup 86}Y-CHX-A''-DTPA-cetuximab alone, {sup 86}Y-CHX-A''-DTPA-cetuximab plus 0.1 mg cetuximab or 0.2 mg cetuximab, the tumor uptake values at 3 days were 29.3 {+-} 4.2, 10.4 {+-} 0.5 and 6.4 {+-} 0.3%ID/g, respectively, demonstrating dose-dependent blockage of the target. Tumors were clearly visualized 1 day after injecting 3.8-4.0 MBq {sup 86}Y-CHX-A''-DTPA-cetuximab. Quantitative PET revealed the highest tumor uptake in LS-174T (29.55 {+-} 2.67%ID/cm{sup 3}) and the lowest tumor uptake in PC-3 (15.92 {+-} 1.55%ID/cm{sup 3}) xenografts at 3 days after injection

  9. [Oligometastasized colorectal cancer-modern treatment strategies].

    Science.gov (United States)

    Binnebösel, M; Lambertz, A; Dejong, K; Neumann, U P

    2018-06-05

    The prognosis of colorectal cancer in UICC stage IV has been improved in the last decades by improvements in interdisciplinary treatment. Treatment strategies for oligometastasized colorectal cancer are developing more and more into an individualized treatment. An overview of the current literature of modern treatment concepts in oligometastasized colorectal cancer UICC stage IV is given. Surgery still has the supreme mandate in resectable colorectal liver metastases, as neoadjuvant and adjuvant treatment strategies to not provide any benefits for these patients. In marginal or non-resectable stages systemic treatment is superior in these patients depending on the prognostic parameters. Also in curative settings local treatment options should be considered as a reasonable additive tool. An interesting treatment approach for isolated liver metastases and non-resectable colorectal cancer is liver transplantation. Irrespective of new developments in treatment strategies for metastasized colorectal cancer, resection of colorectal liver metastases remains the gold standard whenever possible.

  10. Xenograft survival in two species combinations using total-lymphoid irradiation and cyclosporine

    International Nuclear Information System (INIS)

    Knechtle, S.J.; Halperin, E.C.; Bollinger, R.R.

    1987-01-01

    Total lymphoid irradiation (TLI) has profound immunosuppressive actions and has been applied successfully to allotransplantation but not xenotransplantation. Cyclosporine (CsA) has not generally permitted successful xenotransplantation of organs but has not been used in combination with TLI. TLI and CsA were given alone and in combination to rats that were recipients of hamster or rabbit cardiac xenografts. Combined TLI and CsA prolonged survival of hamster-to-rat cardiac xenografts from three days in untreated controls to greater than 100 days in most recipients. TLI alone significantly prolonged rabbit to rat xenograft survival with doubling of survival time. However, combined treatment did not significantly prolong rabbit-to-rat cardiac xenograft survival compared with TLI alone. The hamster and rat are phylogenetically closely related. Transplants from hamsters to rat are concordant xenografts since the time course of unmodified rejection is similar to first-set rejection of allografts. Although the rabbit-to-rat transplant is also between concordant species (average survival of untreated controls: 3.2 days) the rabbit and rat are more distantly related. These results suggest that TLI is an effective immunosuppressant when applied to cardiac xenotransplants in these animal models; that the choice of species critically affects xenograft survival when TLI and/or CsA are used for immunosuppression; and that the closely related species combination tested has markedly prolonged (greater than 100 days) survival using combined TLI and CsA

  11. 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...... pool) of total RNA from left-sided sporadic colorectal carcinomas. We compared normal tissue to carcinoma tissue from Dukes' stages A-D (noninvasive to distant metastasis) and identified 908 known genes and 4,155 ESTs that changed remarkably from normal to tumor tissue. Based on intensive filtering 226...

  12. Dietary B vitamin and methionine intake and MTHFR C677T genotype on risk of colorectal tumors in Lynch syndrome: the GEOLynch cohort study

    NARCIS (Netherlands)

    Jung, A.Y.; van Duijnhoven, F.J.B.; Nagengast, F.M.; Botma, A.; Heine-Broring, R.C.; Kleibeuker, J.H.; Vasen, H.F.A.; Harryvan, J.L.; Winkels, R.M.; Kampman, E.

    2014-01-01

    Purpose: Dietary intake of B vitamins and methionine, essential components of DNA synthesis and methylation pathways, may influence colorectal tumor (CRT) development. The impact of B vitamins on colorectal carcinogenesis in individuals with Lynch syndrome (LS) is unknown but is important given

  13. Inhibition of colon cancer growth by methylselenocysteine-induced angiogenic chemomodulation is influenced by histologic characteristics of the tumor.

    Science.gov (United States)

    Bhattacharya, Arup; Tóth, Károly; Sen, Arindam; Seshadri, Mukund; Cao, Shousong; Durrani, Farukh A; Faber, Erik; Repasky, Elizabeth A; Rustum, Youcef M

    2009-07-01

    Despite an armamentarium that is wide in range, scope of action, and target, chemotherapy has limited success in colorectal cancer (CRC). Novel approaches are needed to overcome tumor barriers to chemotherapy that includes an abnormal tumor vasculature constituting a poor drug delivery system. We have previously shown that 5-methylselenocysteine (MSC) enhances therapeutic efficacy of irinotecan in various human tumor xenografts. We have recently demonstrated that MSC through vascular normalization leads to better tumor vascular function in vivo. In this study, we examined the role of MSC on tumor vasculature, interstitial fluid pressure (IFP) and drug delivery in 2 histologically distinct CRC xenografts, HCT-8 (uniformly poorly differentiated) and HT-29 (moderately differentiated tumor with avascular glandular regions). The presence of specific histologic structures as a barrier to therapy in these xenografts and their clinical relevance was studied using tissue microarray of human surgical samples of CRC. MSC led to a significant tumor growth inhibition, a reduced microvessel density, and a more normalized vasculature in both colorectal xenografts. While IFP was found to be significantly improved in HCT-8, an improved intratumoral doxorubicin delivery seen in both xenografts could explain the observed increase in therapeutic efficacy. Differentiated, glandular, avascular and hypoxic regions that contribute to tumor heterogeneity in HT-29 were also evident in the majority of surgical samples of CRC. Such regions constitute a physical barrier to chemotherapy and can confer drug resistance. Our results indicate that MSC could enhance chemotherapeutic efficacy in human CRC, especially in CRC with few or no hypoxic regions.

  14. Glucose Metabolism of Human Prostate Cancer Mouse Xenografts

    Directory of Open Access Journals (Sweden)

    Hossein Jadvar

    2005-04-01

    Full Text Available We hypothesized that the glucose metabolism of prostate cancer is modulated by androgen. We performed in vivo biodistribution and imaging studies of [F-18] fluorodeoxyglucose (FDG accumulation in androgen-sensitive (CWR-22 and androgen-independent (PC-3 human prostate cancer xenografts implanted in castrated and noncastrated male athymic mice. The growth pattern of the CWR-22 tumor was best approximated by an exponential function (tumor size in mm3 = 14.913 e0.108 × days, R2 = .96, n = 5. The growth pattern of the PC-3 tumor was best approximated by a quadratic function (tumor size in mm3 = 0.3511 × days2 + 49.418 × day −753.33, R2 = .96, n = 3. The FDG accumulation in the CWR-22 tumor implanted in the castrated mice was significantly lower, by an average of 55%, in comparison to that implanted in the noncastrated host (1.27 vs. 2.83, respectively, p < .05. The 3-week maximal standardized uptake value (SUVmax was 0.99 ± 0.43 (mean ± SD for CWR-22 and 1.21 ± 0.32 for PC-3, respectively. The 5-week SUVmax was 1.22 ± 0.08 for CWR-22 and 1.35 ± 0.17 for PC-3, respectively. The background muscle SUVmax was 0.53 ± 0.11. Glucose metabolism was higher in the PC-3 tumor than in the CWR-22 tumor at both the 3-week (by 18% and the 5-week (by 9.6% micro-PET imaging sessions. Our results support the notions that FDG PET may be useful in the imaging evaluation of response to androgen ablation therapy and in the early prediction of hormone refractoriness in men with metastatic prostate cancer.

  15. A Xenograft Model of Vestibular Schwannoma and Hearing Loss.

    Science.gov (United States)

    Dinh, Christine T; Bracho, Olena; Mei, Christine; Bas, Esperanza; Fernandez-Valle, Cristina; Telischi, Fred; Liu, Xue-Zhong

    2018-03-19

    Microsurgical implantation of mouse merlin-deficient Schwann cells (MD-SC) into the cerebellopontine angle of immunodeficient rats will initiate tumor formation, hearing loss, and vestibular dysfunction. The progress in identifying effective drug therapies for treatment of Neurofibromatosis type II (NF2) is limited by the availability of animal models of VS that develop hearing loss and imbalance. A microsurgical technique for implanting MD-SCs onto the cochleovestibular nerve of rats was developed. Ten Rowett Nude rats were implanted with either ∼10 MD-SCs expressing luciferase (N = 5) or vehicle (N = 5). Rats received bioluminescence imaging, auditory brainstem response testing, and were observed for head tilt every 2 weeks after surgery, for a total of 6 weeks. Tumors were harvested and processed with hematoxylin & eosin staining and immunohistochemistry was performed for S100. Rats implanted with MD-SCs developed significantly higher tumor bioluminescence measurements and hearing threshold shifts at multiple frequencies by the 4th and 6th weeks post-implantation, compared with control rats. Rats implanted with MD-SCs also developed gross tumor. The tumor volume was significantly greater than nerve volumes obtained from rats in the control group. All rats with tumors developed a head tilt, while control rats had no signs of vestibular dysfunction. Tumors demonstrated histological features of schwannoma and express S100. Using this microsurgical technique, this xenograft rat model of VS develops tumors involving the cochleovestibular nerve, shifts in hearing thresholds, and vestibular dysfunction. This animal model can be used to investigate tumor-mediated hearing loss and perform preclinical drug studies for NF2.

  16. Quantitative PET of EGFR expression in xenograft-bearing mice using {sup 64}Cu-labeled cetuximab, a chimeric anti-EGFR monoclonal antibody

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Weibo; Chen, Kai; He, Lina; Cao, Qizhen; Chen, Xiaoyuan [Stanford University School of Medicine, The Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Stanford, CA (United States); Koong, Albert [Stanford University School of Medicine, Department of Radiation Oncology, Stanford, CA (United States)

    2007-06-15

    Cetuximab, a chimeric monoclonal antibody targeting epidermal growth factor receptor (EGFR) on the surface of cancer cells, was approved by the FDA to treat patients with metastatic colorectal cancer. It is currently also in advanced-stage development for the treatment of several other solid tumors. Here we report for the first time the quantitative positron emission tomography (PET) imaging of EGFR expression in xenograft-bearing mice using {sup 64}Cu-labeled cetuximab. We conjugated cetuximab with macrocyclic chelating agent 1,4,7,10-tetraazadodecane-N,N',N'',N'''-tetraacetic acid (DOTA), labeled with {sup 64}Cu, and tested the resulting {sup 64}Cu-DOTA-cetuximab in seven xenograft tumor models. The tracer uptake measured by PET was correlated with the EGFR expression quantified by western blotting. The estimated human dosimetry based on the PET data in Sprague-Dawley rats was also calculated. MicroPET imaging showed that {sup 64}Cu-DOTA-cetuximab had increasing tumor activity accumulation over time in EGFR-positive tumors but relatively low uptake in EGFR-negative tumors at all times examined (<5%ID/g). There was a good correlation (R {sup 2} = 0.80) between the tracer uptake (measured by PET) and the EGFR expression level (measured by western blotting). Human dosimetry estimation indicated that the tracer may be safely administered to human patients for tumor diagnosis, with the dose-limiting organ being the liver. The success of EGFR-positive tumor imaging using {sup 64}Cu-DOTA-cetuximab can be translated into the clinic to characterize the pharmacokinetics, to select the right population of patients for EGFR-targeted therapy, to monitor the therapeutic efficacy of anti-EGFR treatment, and to optimize the dosage of either cetuximab alone or cetuximab in combination with other therapeutic agents. (orig.)

  17. Impact of MLH1 expression on tumor evolution after curative surgical tumor resection in a murine orthotopic xenograft model for human MSI colon cancer.

    Science.gov (United States)

    Meunier, Katy; Ferron, Marianne; Calmel, Claire; Fléjou, Jean-François; Pocard, Marc; Praz, Françoise

    2017-09-01

    Colorectal cancers (CRCs) displaying microsatellite instability (MSI) most often result from MLH1 deficiency. The aim of this study was to assess the impact of MLH1 expression per se on tumor evolution after curative surgical resection using a xenograft tumor model. Transplantable tumors established with the human MLH1-deficient HCT116 cell line and its MLH1-complemented isogenic clone, mlh1-3, were implanted onto the caecum of NOD/SCID mice. Curative surgical resection was performed at day 10 in half of the animals. The HCT116-derived tumors were more voluminous compared to the mlh1-3 ones (P = .001). Lymph node metastases and peritoneal carcinomatosis occurred significantly more often in the group of mice grafted with HCT116 (P = .007 and P = .035, respectively). Mlh1-3-grafted mice did not develop peritoneal carcinomatosis or liver metastasis. After surgical resection, lymph node metastases only arose in the group of mice implanted with HCT116 and the rate of cure was significantly lower than in the mlh1-3 group (P = .047). The murine orthotopic xenograft model based on isogenic human CRC cell lines allowed us to reveal the impact of MLH1 expression on tumor evolution in mice who underwent curative surgical resection and in mice whose tumor was left in situ. Our data indicate that the behavior of MLH1-deficient CRC is not only governed by mutations arising in genes harboring microsatellite repeated sequences but also from their defect in MLH1 as such. © 2017 Wiley Periodicals, Inc.

  18. Quantitative PET of EGFR expression in xenograft-bearing mice using 64Cu-labeled cetuximab, a chimeric anti-EGFR monoclonal antibody

    International Nuclear Information System (INIS)

    Cai, Weibo; Chen, Kai; He, Lina; Cao, Qizhen; Chen, Xiaoyuan; Koong, Albert

    2007-01-01

    Cetuximab, a chimeric monoclonal antibody targeting epidermal growth factor receptor (EGFR) on the surface of cancer cells, was approved by the FDA to treat patients with metastatic colorectal cancer. It is currently also in advanced-stage development for the treatment of several other solid tumors. Here we report for the first time the quantitative positron emission tomography (PET) imaging of EGFR expression in xenograft-bearing mice using 64 Cu-labeled cetuximab. We conjugated cetuximab with macrocyclic chelating agent 1,4,7,10-tetraazadodecane-N,N',N'',N'''-tetraacetic acid (DOTA), labeled with 64 Cu, and tested the resulting 64 Cu-DOTA-cetuximab in seven xenograft tumor models. The tracer uptake measured by PET was correlated with the EGFR expression quantified by western blotting. The estimated human dosimetry based on the PET data in Sprague-Dawley rats was also calculated. MicroPET imaging showed that 64 Cu-DOTA-cetuximab had increasing tumor activity accumulation over time in EGFR-positive tumors but relatively low uptake in EGFR-negative tumors at all times examined ( 2 0.80) between the tracer uptake (measured by PET) and the EGFR expression level (measured by western blotting). Human dosimetry estimation indicated that the tracer may be safely administered to human patients for tumor diagnosis, with the dose-limiting organ being the liver. The success of EGFR-positive tumor imaging using 64 Cu-DOTA-cetuximab can be translated into the clinic to characterize the pharmacokinetics, to select the right population of patients for EGFR-targeted therapy, to monitor the therapeutic efficacy of anti-EGFR treatment, and to optimize the dosage of either cetuximab alone or cetuximab in combination with other therapeutic agents. (orig.)

  19. Robotic colorectal surgery: previous laparoscopic colorectal experience is not essential.

    Science.gov (United States)

    Sian, Tanvir Singh; Tierney, G M; Park, H; Lund, J N; Speake, W J; Hurst, N G; Al Chalabi, H; Smith, K J; Tou, S

    2018-06-01

    A background in minimally invasive colorectal surgery (MICS) has been thought to be essential prior to robotic-assisted colorectal surgery (RACS). Our aim was to determine whether MICS is essential prior to starting RACS training based on results from our initial experience with RACS. Two surgeons from our centre received robotic training through the European Academy of Robotic Colorectal Surgery (EARCS). One surgeon had no prior formal MICS training. We reviewed the first 30 consecutive robotic colorectal procedures from a prospectively maintained database between November 2014 and January 2016 at our institution. Fourteen patients were male. Median age was 64.5 years (range 36-82) and BMI was 27.5 (range 20-32.5). Twelve procedures (40%) were performed by the non-MICS-trained surgeon: ten high anterior resections (one conversion), one low anterior resection and one abdomino-perineal resection of rectum (APER). The MICS-trained surgeon performed nine high and four low anterior resections, one APER and in addition three right hemicolectomies and one abdominal suture rectopexy. There were no intra-operative complications and two patients required re-operation. Median post-operative stay was five days (range 1-26). There were two 30-day re-admissions. All oncological resections had clear margins and median node harvest was 18 (range 9-39). Our case series demonstrates that a background in MICS is not essential prior to starting RACS training. Not having prior MICS training should not discourage surgeons from considering applying for a robotic training programme. Safe and successful robotic colorectal services can be established after completing a formal structured robotic training programme.

  20. 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.

  1. Increased suppression of oncolytic adenovirus carrying mutant k5 on colorectal tumor

    International Nuclear Information System (INIS)

    Fan Junkai; Xiao Tian; Gu Jinfa; Wei Na; He Lingfeng; Ding Miao; Liu Xinyuan

    2008-01-01

    Angiogenesis plays a key role in the development of a wide variety of malignant tumors. The approach of targeting antiangiogenesis has become an important field of cancer gene therapy. In this study, the antiangiogenesis protein K5 (the kringle 5 of human plasminogen) has been mutated by changing leucine71 to arginine to form mK5. Then the ZD55-mK5, which is an oncolytic adenovirus expressing mK5, was constructed. It showed stronger inhibition on proliferation of human umbilical vein endothelial cell. Moreover, in tube formation and embryonic chorioallantoic membrane assay, ZD55-mK5 exhibited more effective antiangiogenesis than ZD55-K5. In addition, ZD55-mK5 generated obvious suppression on the growth of colorectal tumor xenografts and prolonged the life span of nude mice. These results indicate that ZD55-mK5 is a potent agent for inhibiting the tumor angiogenesis and tumor growth

  2. Cetuximab improves AZD6244 antitumor activity in colorectal cancer HT29 cells in vitro and in nude mice by attenuating HER3/Akt pathway activation.

    Science.gov (United States)

    Zhang, Qin; Xiao, He; Jin, Feng; Li, Mengxia; Luo, Jia; Wang, Ge

    2018-07-01

    The present study investigated the molecular mechanism by which the epidermal growth factor receptor (EGFR) inhibitor cetuximab enhances the antitumor activity of the mitogen-activated protein kinase kinase (MEK) inhibitor AZD6244 in colorectal cancer HT29 cells. HT29 cells were treated with AZD6244 plus cetuximab and then subjected to the following assays: Cell Counting kit-8, BrdU-incorporation, flow cytometric cell cycle distribution and apoptosis analysis, western blot analysis, and nude mouse xenografts. The combination of AZD6244 and cetuximab significantly reduced HT29 cell viability and proliferation compared with AZD6244 alone. The combination treatment reduced the IC 50 value from 108.12±10.05 to 28.45±1.92 nM. AZD6244 and cetuximab also induced cell cycle arrest at G1 phase and reduced S phase (88.53% vs. 93.39%, P=0.080; 8.73% vs. 4.24%, P=0.082, respectively). Combination of AZD6244 with cetuximab significantly induced tumor cells apoptosis (14.61% vs. 8.99%, P=0.046). Inhibition of EGFR activity using cetuximab partially abrogated the feedback-activation of phosphorylated receptor tyrosine-protein kinase erB-3 (p-HER3) and p-AKT serine/threonine kinase (AKT), as well as prevented reactivation of p-extracellular regulated kinase (ERK) conferred by AZD6244 treatment. Combination of AZD6244 and cetuximab also inhibited HT29 cell xenograft growth in nude mice and suppressed HER3 and p-AKT levels in xenografts. The EGFR inhibitor cetuximab enhanced the antitumor activity of the MEK inhibitor AZD6244 in colorectal cells in vitro and in vivo . Co-inhibition of MEK and EGFR may be a promising treatment strategy in colorectal cancers.

  3. Minilaparoscopic Colorectal Resections: Technical Note

    Directory of Open Access Journals (Sweden)

    S. Bona

    2012-01-01

    Full Text Available Laparoscopic colorectal resections have been shown to provide short-term advantages in terms of postoperative pain, general morbidity, recovery, and quality of life. To date, long-term results have been proved to be comparable to open surgery irrefutably only for colon cancer. Recently, new trends keep arising in the direction of minimal invasiveness to reduce surgical trauma after colorectal surgery in order to improve morbidity and cosmetic results. The few reports available in the literature on single-port technique show promising results. Natural orifices endoscopic techniques still have very limited application. We focused our efforts in standardising a minilaparoscopic technique (using 3 to 5 mm instruments for colorectal resections since it can provide excellent cosmetic results without changing the laparoscopic approach significantly. Thus, there is no need for a new learning curve as minilaparoscopy maintains the principle of instrument triangulation. This determines an undoubted advantage in terms of feasibility and reproducibility of the procedure without increasing operative time. Some preliminary experiences confirm that minilaparoscopic colorectal surgery provides acceptable results, comparable to those reported for laparoscopic surgery with regard to operative time, morbidity, and hospital stay. Randomized controlled studies should be conducted to confirm these early encouraging results.

  4. 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...

  5. 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.

  6. 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.

  7. 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.

  8. Optimisation of colorectal cancer treatment

    NARCIS (Netherlands)

    Broek, Colette Bernadine Maria-Theresia van den

    2014-01-01

    Colorectal cancer is one of the most common cancers worldwide. Although there have been several improvements in screening, staging, and treatment in the past decades, survival differences remain. For example among certain subgroups of patients, such as elderly patients and patients with

  9. Wound Disruption Following Colorectal Operations.

    Science.gov (United States)

    Moghadamyeghaneh, Zhobin; Hanna, Mark H; Carmichael, Joseph C; Mills, Steven; Pigazzi, Alessio; Nguyen, Ninh T; Stamos, Michael J

    2015-12-01

    Postoperative wound disruption is associated with high morbidity and mortality. We sought to identify the risk factors and outcomes of wound disruption following colorectal resection. The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database was used to examine the clinical data of patients who underwent colorectal resection from 2005 to 2013. Multivariate regression analysis was performed to identify risk factors of wound disruption. We sampled a total of 164,297 patients who underwent colorectal resection. Of these, 2073 (1.3 %) had wound disruption. Patients with wound disruption had significantly higher mortality (5.1 vs. 1.9 %, AOR: 1.46, P = 0.01). The highest risk of wound disruption was seen in patients with wound infection (4.8 vs. 0.9 %, AOR: 4.11, P disruption such as chronic steroid use (AOR: 1.71, P disruption compared to open surgery (AOR: 0.61, P disruption occurs in 1.3 % of colorectal resections, and it correlates with mortality of patients. Wound infection is the strongest predictor of wound disruption. Chronic steroid use, obesity, severe COPD, prolonged operation, non-elective admission, and serum albumin level are strongly associated with wound disruption. Utilization of the laparoscopic approach may decrease the risk of wound disruption when possible.

  10. HISTOMORPHOLOGICAL STUDY OF COLORECTAL MALIGNANCIES

    Directory of Open Access Journals (Sweden)

    Sarvesh

    2015-07-01

    Full Text Available BACKGROUND: Colorectal cancer is the most common cancer in men and in women worldwide. Incidence rates of colorectal cancer vary 10 - fold in both sexes worldwide, Within Asia, the incidence rates vary widely and are uniformly low in all south Asian countries and high i n all developed Asian countries. Fortunately, the age adjusted incidence rates of colorectal cancer in all the Indian cancer registries are very close to the lowest rates in the world. The present study is under taken to study the prevalence and types of c olorectal cancer among the patients in the rural population in and around Chidambaram. OBJECTIVES: To study the prevalence of malignant colorectal neoplasms among the speci mens received in the Department of Pathology and the gross and histomorphological pa ttern of the lesions and finally to correlate the findings with clinical data. METHOD: The materials consisted of 68 specimens who were submitted to the Department of Pathology, during the period of Jan 2008 - Dec 2012. Data collected and entered in MS - Excel and were analyzed using SPSS - 16. RESULTS : Out of 8454 colonoscopic specimens, 68(0.8% showed colorectal malignancy. A higher frequency of colorectal was seen in 6 th decade. Out of 68 specimens of malignant neoplasms majority were Carcinoma of the Rectum (79.41% followed in decreasing order of frequency by malignant lesions of descending colon(8.82%, ascending and Sigmoid colon (4.41% each, recto - sigmoid (2.94% and cecum (2.63%, and transverse colon (2.63%. Youngest patient was 19 years old and the o ldest patient was 80 years old with a mean age of 49.5 years and median age of 50 years. CONCLUSION: Colorectal cancer is a common and lethal disease. The adenoma carcinoma. S equence offers a window of opportunity in which the precursor lesion or early car cinoma can be removed endoscopically to prevent systematic disease. The result of a careful and systematic examination of surgical specimens from patients with

  11. Diet, lifestyle, and molecular alterations that drive colorectal carcinogenesis

    NARCIS (Netherlands)

    Diergaarde, B.

    2004-01-01

    Environmental factors have been repeatedly implicated in the etiology of colorectal cancer, and much is known about the molecular events involved in colorectal carcinogenesis. The relationships between environmental risk factors and the molecular alterations that drive colorectal carcinogenesis are

  12. Modifiable risk factors and colorectal adenomas among those at high risk of colorectal cancer

    NARCIS (Netherlands)

    Botma, A.

    2011-01-01

    Epidemiological studies have identified several modifiable risk factors for colorectal neoplasms in the general population. However, associations between modifiable risk factors, including body mass index (BMI), smoking, alcohol consumption and dietary patterns, and colorectal neoplasms in two

  13. Establishment and characterization of a new cell line derived from human colorectal laterally spreading tumor

    Science.gov (United States)

    Wang, Xin-Ying; Lai, Zhou-Sheng; Yeung, Chung-Man; Wang, Ji-De; Deng, Wen; Li, Hoi Yee; Han, Yu-Jing; Kung, Hsiang-Fu; Jiang, Bo; Lin, Marie Chia-mi

    2008-01-01

    AIM: To study the molecular mechanism of laterally spreading tumor (LST), a cell line [Laterally Spreading Tumor-Rectum 1 (LST-R1)] was derived and the characteristics of this cell line were investigated. METHODS: A new cell line (LST-R1) originated from laterally spreading tumor was established. Properties of the cell line were characterized using scanning and transmission electron microscopy, immunohistochemistry method, cytogenetic analysis and nude mice xenograft experiments. In vitro invasion assay, cDNA microarray and Western blotting were used to compare the difference between the LST-R1 and other colorectal cancer cell lines derived from prudent colon cancer. RESULTS: Our study demonstrated that both epithelial special antigen (ESA) and cytokeratin-20 (CK20) were expressed in LST-R1. The cells presented microvilli and tight junction with large nuclei. The karyotypic analysis showed hyperdiploid features with structural chromosome aberrations. The in vivo tumorigenicity was also demonstrated in nude mice xenograft experiments. The invasion assay suggested this cell line has a higher invasive ability. cDNA microarray and Western blotting show the loss of the expression of E-cadherin in LST-R1 cells. CONCLUSION: We established and characterized a colorectal cancer cell line, LST-R1 and LST-R1 has an obvious malignant tendency, which maybe partially attributed to the changes of the expression of some adhesion molecules, such as E-cadherin. It is also a versatile tool for exploring the original and progressive mechanisms of laterally spreading tumor and the early colon cancer genesis. PMID:18300345

  14. Dai-Kenchu-To, a Herbal Medicine, Attenuates Colorectal Distention-induced Visceromotor Responses in Rats.

    Science.gov (United States)

    Nakaya, Kumi; Nagura, Yohko; Hasegawa, Ryoko; Ito, Hitomi; Fukudo, Shin

    2016-10-30

    Dai-kenchu-to (DKT), a traditional Japanese herbal medicine, is known to increase gastrointestinal motility and improve ileal function. We tested our hypotheses that (1) pretreatment with DKT would block the colorectal distention-induced visceromotor response in rats, and (2) pretreatment with DKT would attenuate colorectal distention-induced adrenocorticotropic hormone (ACTH) release and anxiety-related behavior. Rats were pretreated with vehicle or DKT (300 mg/kg/5 mL, per os). Visceromotor responses were analyzed using electromyography in response to colorectal distention (10, 20, 40, 60, and 80 mmHg for 20 seconds at 3-minutes intervals). Anxiety-related behavior was measured during exposure to an elevated-plus maze after colorectal distention. Plasma ACTH and serum corticosterone levels were measured after exposure to the elevated-plus maze. Colorectal distention produced robust contractions of the abdominal musculature, graded according to stimulus intensity, in vehicle-treated rats. At 40, 60, and 80 mmHg of colorectal distention, the visceromotor responses of DKT-treated rats was significantly lower than that of vehicle-treated rats. At 80 mmHg, the amplitude was suppressed to approximately one-third in DKT-treated rats, compared with that in vehicle-treated rats. Smooth muscle compliance and the velocity of accommodation to 60 mmHg of stretching did not significantly differ between the vehicle-treated and DKT-treated rats. Similarly, the DKT did not influence colorectal distention-induced ACTH release, corticosterone levels, or anxiety-related behavior in rats. Our results suggest that DKT attenuates the colorectal distention-induced visceromotor responses, without increasing smooth muscle compliance, ACTH release or anxiety-related behavior in rats.

  15. miR-330 regulates the proliferation of colorectal cancer cells by targeting Cdc42

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yuefeng [The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001 (China); Zhu, Xiaolan; Xu, Wenlin [The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001 (China); Wang, Dongqing [The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001 (China); Yan, Jinchuan, E-mail: jiangdalyf2009@126.com [The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001 (China)

    2013-02-15

    Highlights: ► miR-330 was inversely correlated with Cdc42 in colorectal cancer cells. ► Elevated miR-330 suppressed cell proliferation in vivo and in vitro. ► Elevated miR-330 mimicked the effect of Cdc42 knockdown. ► Restoration of Cdc42 could partially attenuate the effects of miR-330. -- Abstract: MicroRNAs are small non-coding RNA molecules that play important roles in the multistep process of colorectal carcinoma (CRC) development. However, the miRNA–mRNA regulatory network is far from being fully understood. The objective of this study was to investigate the expression and the biological roles of miR-330 in colorectal cancer cells. Cdc42, one of the best characterized members of the Rho GTPase family, was found to be up-regulated in several types of human tumors including CRC and has been implicated in cancer initiation and progression. In the present study, we identified miR-330, as a potential regulator of Cdc42, was found to be inversely correlated with Cdc42 expression in colorectal cancer cell lines. Ectopic expression of miR-330 down-regulated Cdc42 expression at both protein and mRNA level, mimicked the effect of Cdc42 knockdown in inhibiting proliferation, inducing G1 cell cycle arrest and apoptosis of the colorectal cancer cells, whereas restoration of Cdc42 could partially attenuate the effects of miR-330. In addition, elevated expression of miR-330 could suppress the immediate downstream effectors of Cdc42 and inhibit the growth of colorectal cancer cells in vivo. To sum up, our results establish a role of miR-330 in negatively regulating Cdc42 expression and colorectal cancer cell proliferation. They suggest that manipulating the expression level of Cdc42 by miR-330 has the potential to influence colorectal cancer progression.

  16. miR-330 regulates the proliferation of colorectal cancer cells by targeting Cdc42

    International Nuclear Information System (INIS)

    Li, Yuefeng; Zhu, Xiaolan; Xu, Wenlin; Wang, Dongqing; Yan, Jinchuan

    2013-01-01

    Highlights: ► miR-330 was inversely correlated with Cdc42 in colorectal cancer cells. ► Elevated miR-330 suppressed cell proliferation in vivo and in vitro. ► Elevated miR-330 mimicked the effect of Cdc42 knockdown. ► Restoration of Cdc42 could partially attenuate the effects of miR-330. -- Abstract: MicroRNAs are small non-coding RNA molecules that play important roles in the multistep process of colorectal carcinoma (CRC) development. However, the miRNA–mRNA regulatory network is far from being fully understood. The objective of this study was to investigate the expression and the biological roles of miR-330 in colorectal cancer cells. Cdc42, one of the best characterized members of the Rho GTPase family, was found to be up-regulated in several types of human tumors including CRC and has been implicated in cancer initiation and progression. In the present study, we identified miR-330, as a potential regulator of Cdc42, was found to be inversely correlated with Cdc42 expression in colorectal cancer cell lines. Ectopic expression of miR-330 down-regulated Cdc42 expression at both protein and mRNA level, mimicked the effect of Cdc42 knockdown in inhibiting proliferation, inducing G1 cell cycle arrest and apoptosis of the colorectal cancer cells, whereas restoration of Cdc42 could partially attenuate the effects of miR-330. In addition, elevated expression of miR-330 could suppress the immediate downstream effectors of Cdc42 and inhibit the growth of colorectal cancer cells in vivo. To sum up, our results establish a role of miR-330 in negatively regulating Cdc42 expression and colorectal cancer cell proliferation. They suggest that manipulating the expression level of Cdc42 by miR-330 has the potential to influence colorectal cancer progression

  17. Oxaliplatin immuno hybrid nanoparticles for active targeting: an approach for enhanced apoptotic activity and drug delivery to colorectal tumors.

    Science.gov (United States)

    Tummala, Shashank; Gowthamarajan, K; Satish Kumar, M N; Wadhwani, Ashish

    2016-06-01

    Tumor necrosis factor related apoptosis inducing ligand (TRAIL) proved to be a promising new target for colorectal cancer treatment. Elevated expression of TRAIL protein in tumor cells distinguishes it from healthy cells, thereby delivering the drug at the specific site. Here, we formulated oxaliplatin immunohybrid nanoparticles (OIHNPs) to deliver oxaliplatin and anti-TRAIL for colorectal cancer treatment in xenograft tumor models. The polymeric chitosan layer binds to the lipid film with the mixture of phospholipids by an ultra sound method followed by conjugating with thiolated antibody using DSPE-PEG-mal3400, resulting in the formation of OIHNPs. The polymer layer helps in more encapsulation of the drug (71 ± 0.09%) with appreciable particle size (95 ± 0.01 nm), and lipid layer prevents degradation of the drug in serum by preventing nanoparticle aggregation. OIHNPs have shown a 4-fold decrease in the IC50 value compared to oxaliplatin in HT-29 cells by the MTT assay. These immuno-nanoparticles represent the successful uptake and internalization of oxaliplatin in HT-29 cells rather than in MCF-7 cells determined by triple fluorescence method. Apoptotic activity in vitro of OIHNPs was determined by the change in the mitochondria membrane potential that further elevates its anti-tumor property. Furthermore, the conjugated nanoparticles can effectively deliver the drug to the tumor sites, which can be attributed to its ability in reducing tumor mass and tumor volume in xenograft tumor models in vivo along with sustaining its release in vitro. These findings indicated that the oxaliplatin immuno-hybrid nanoparticles would be a promising nano-sized active targeted formulation for colorectal-tumor targeted therapy.

  18. A national study of breast and colorectal cancer patients' decision-making for novel personalized medicine genomic diagnostics.

    Science.gov (United States)

    Issa, Amalia M; Tufail, Waqas; Atehortua, Nelson; McKeever, John

    2013-05-01

    Molecular diagnostics are increasingly being used to help guide decision-making for personalized medical treatment of breast and colorectal cancer patients. The main aim of this study was to better understand and determine breast and colorectal cancer patients' decision-making strategies and the trade-offs they make in deciding about characteristics of molecular genomic diagnostics for breast and colorectal cancer. We surveyed a nationally representative sample of 300 breast and colorectal cancer patients using a previously developed web-administered instrument. Eligibility criteria included patients aged 18 years and older with either breast or colorectal cancer. We explored several attributes and attribute levels of molecular genomic diagnostics in 20 scenarios. Our analysis revealed that both breast and colorectal cancer patients weighted the capability of molecular genomic diagnostics to determine the probability of treatment efficacy as being of greater importance than information provided to detect adverse events. The probability of either false-positive or -negative results was ranked highly as a potential barrier by both breast and colorectal patients. However, 78.6% of breast cancer patients ranked the possibility of a 'false-negative test result leading to undertreatment' higher than the 'chance of a false positive, which may lead to overtreatment' (68%). This finding contrasted with the views of colorectal cancer patients who ranked the chance of a false positive as being of greater concern than a false negative (72.8 vs 63%). Overall, cancer patients exhibited a high willingness to accept and pay for genomic diagnostic tests, especially among breast cancer patients. Cancer patients seek a test accuracy rate of 90% or higher. Breast and colorectal cancer patients' decisions about genomic diagnostics are influenced more by the probability of being cured than by avoiding potential severe adverse events. This study provides insights into the relative weight

  19. Immunogenomic Classification of Colorectal Cancer and Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Jessica Roelands

    2017-10-01

    Full Text Available The immune system has a substantial effect on colorectal cancer (CRC progression. Additionally, the response to immunotherapeutics and conventional treatment options (e.g., chemotherapy, radiotherapy and targeted therapies is influenced by the immune system. The molecular characterization of colorectal cancer (CRC has led to the identification of favorable and unfavorable immunological attributes linked to clinical outcome. With the definition of consensus molecular subtypes (CMSs based on transcriptomic profiles, multiple characteristics have been proposed to be responsible for the development of the tumor immune microenvironment and corresponding mechanisms of immune escape. In this review, a detailed description of proposed immune phenotypes as well as their interaction with different therapeutic modalities will be provided. Finally, possible strategies to shift the CRC immune phenotype towards a reactive, anti-tumor orientation are proposed per CMS.

  20. 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.

  1. 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.

  2. Matrigel alters the pathophysiology of orthotopic human breast adenocarcinoma xenografts with implications for nanomedicine evaluation.

    Science.gov (United States)

    Shuhendler, Adam J; Prasad, Preethy; Cai, Ping; Hui, Kelvin K W; Henderson, Jeffrey T; Rauth, Andrew M; Wu, Xiao Yu

    2013-08-01

    Matrigel, a mouse sarcoma-derived basement membrane protein mixture, is frequently used to facilitate human tumor xenograft growth in rodents. Despite its known effects on tumor growth and metastasis, its impact on tumor pathophysiology and preclinical evaluation of nanomedicines in tumor xenografts has not been reported previously. Herein bilateral MDA435 tumors were established orthotopically with (Mat+) or without (Mat-) co-injection of Matrigel. Tumor perfusion, morphology and nanoparticle retention were evaluated. As compared to Mat- tumors, Mat+tumors exhibited enhanced vascular perfusion and lymphatic flow, greater blood vessel and lymphatic growth within the tumor core, and more deformation and collapse of lymphatics in tumor-associated lymph nodes. These changes were accompanied by reduced nanoparticle retention in Mat+tumors. The results suggest that Matrigel is not a passive medium for tumor growth, but rather significantly alters long-term tumor architecture. These findings have significant implications for the evaluation of therapeutic nanomedicine in xenograft mouse models. Matrigel is utilized in facilitating human tumor xenograft growth in rodents. The authors demonstrate that Matrigel is not a passive medium for tumor growth; instead it significantly alters long-term tumor architecture, with major implications in the evaluation of therapeutic nanomedicine in xenograft mouse models. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Systematic analysis of a xenograft mice model for KSHV+ primary effusion lymphoma (PEL.

    Directory of Open Access Journals (Sweden)

    Lu Dai

    Full Text Available Kaposi's sarcoma-associated herpesvirus is the causative agent of primary effusion lymphoma (PEL, which arises preferentially in the setting of infection with human immunodeficiency virus (HIV. Even with standard cytotoxic chemotherapy, PEL continues to cause high mortality rates, requiring the development of novel therapeutic strategies. PEL xenograft models employing immunodeficient mice have been used to study the in vivo effects of a variety of therapeutic approaches. However, it remains unclear whether these xenograft models entirely reflect clinical presentations of KSHV(+ PEL, especially given the recent description of extracavitary solid tumor variants arising in patients. In addition, effusion and solid tumor cells propagated in vivo exhibit unique biology, differing from one another or from their parental cell lines propagated through in vitro culture. Therefore, we used a KSHV(+ PEL/BCBL-1 xenograft model involving non-obese diabetic/severe-combined immunodeficient (NOD/SCID mice, and compared characteristics of effusion and solid tumors with their parent cell culture-derived counterparts. Our results indicate that although this xenograft model can be used for study of effusion and solid lymphoma observed in patients, tumor cells in vivo display unique features to those passed in vitro, including viral lytic gene expression profile, rate of solid tumor development, the host proteins and the complex of tumor microenvironment. These items should be carefully considered when the xenograft model is used for testing novel therapeutic strategies against KSHV-related lymphoma.

  4. Nutrients, Foods, and Colorectal Cancer Prevention

    OpenAIRE

    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, fo...

  5. Attributable causes of colorectal cancer in China

    OpenAIRE

    Gu, Meng-Jia; Huang, Qiu-Chi; Bao, Cheng-Zhen; Li, Ying-Jun; Li, Xiao-Qin; Ye, Ding; Ye, Zhen-Hua; Chen, Kun; Wang, Jian-Bing

    2018-01-01

    Background Colorectal cancer is the 4th common cancer in China. Most colorectal cancers are due to modifiable lifestyle factors, but few studies have provided a systematic evidence-based assessment of the burden of colorectal cancer incidence and mortality attributable to the known risk factors in China. Methods We estimated the population attributable faction (PAF) for each selected risk factor in China, based on the prevalence of exposure around 2000 and relative risks from cohort studies a...

  6. Management of colorectal cancer and diabetes

    OpenAIRE

    Yao, Caroline; Nash, Guy F; Hickish, Tamas

    2014-01-01

    Colorectal cancer is associated with diabetes mellitus and both of these common conditions are often managed together by a surgeon. The surgical focus is usually upon cancer treatment rather than diabetes management. The relationship between colorectal cancer and diabetes is a complex one and can raise problems in both diagnosis and the management of patients with both conditions. This literature review explores the relationship between diabetes, diabetic treatment and colorectal cancer and a...

  7. Predictors of advanced colorectal neoplasia for colorectal cancer screening.

    Science.gov (United States)

    Wong, Martin C S; Lam, Thomas Y T; Tsoi, Kelvin K F; Chan, Victor C W; Hirai, Hoyee W; Ching, Jessica Y L; Sung, Joseph J Y

    2014-05-01

    The Asia-Pacific Colorectal Screening (APCS) score based on age, gender, family history, and smoking is useful to predict advanced colorectal neoplasia (ACN) in asymptomatic Asian subjects. To evaluate the factors in addition to those of APCS associated with ACN colonoscopic findings. Data from 5,220 asymptomatic subjects aged between 50 and 70 years who underwent screening colonoscopy in a community center between 2008 and 2012 were analyzed. One binary logistic regression analysis was conducted in 2013 with the presence of ACN or cancer as the outcome, controlling for APCS score, alcohol consumption, BMI, hypertension, and other chronic diseases as independent variables. The average participant age was 57.7 years (SD=4.9) and 47.5% were men. Advanced neoplasms or cancers were identified at colonoscopy in 5.6% of all screening participants. From multivariate regression analysis, APCS score≥4 (adjusted OR [AOR]=1.74, 95% CI=1.34, 2.25, pstatistic of APCS score alone was 0.560 (95% CI=0.524, 0.595, p=0.001) and that of APCS score plus BMI, hypertension, and alcohol consumption was 0.613 (95% CI=0.578, 0.648, p<0.001). Alcohol consumption, hypertension, and BMI are independent predictors of ACN, which could be incorporated into the APCS for prioritizing Asian asymptomatic subjects for colorectal cancer screening. Copyright © 2014. Published by Elsevier Inc.

  8. Colorectal cancer: what's new in 1992

    International Nuclear Information System (INIS)

    Rivoire, M.

    1992-01-01

    Five studies presented at the 1992 ASCO meeting are analysed. Kligerman's study was designed to determine if pre-treatment with WR-2721 could p rotect normal tissues from the toxicities induced by radiation therapy (in 100 patients with an advanced rectal cancer). This pre-treatment resulted in a 13% reduction of moderate and severe acute toxicity. No WR-2721 patient experienced moderate or severe late toxicities compared to five in the group without pre-treatment. Minski studied the acute toxicity (during treatment and two weeks after) of combined pelvic radiation therapy, 5-FU and leucovorin when delivered pre-operatively (16 patients) versus post-operatively (25 patients) in patients with rectal cancer. The final report of the inter group study of 5-FU plus levamisole as adjuvant therapy for stage C colon cancer was made by Moertel. With a median follow-up time of 5.5 years, the 5-FU plus levamisole treatment has reduced the recurrence rate by 39%, the cancer related death rate by 32% and the overall death rate by 31%. Most of the recurrences occurred during the first two years. There was a decrease in the liver, great omentum, peritoneum and lung metastases, but there was no modification in loco-regional recurrence rate. Welt presented a phase I/II study of radio-immunotherapy with I 131 monoclonal antibody A33 in patients with advanced colorectal carcinoma. Results were characterized by major hematologic toxicity and minor tumor response rate. Heiss undertook a prospective study to evaluate the influence of homologous blood transfusion on recurrence rate after colorectal cancer surgery. Fifty-eight patients receiving autologous blood transfusion were compared with sixty-two patients receiving homologous transfusion. With a median follow-up of 21 months a higher recurrence rate was found in the homologous group (29.4% versus 16.7%)

  9. Endogenous retrovirus induces leukemia in a xenograft mouse model for primary myelofibrosis.

    Science.gov (United States)

    Triviai, Ioanna; Ziegler, Marion; Bergholz, Ulla; Oler, Andrew J; Stübig, Thomas; Prassolov, Vladimir; Fehse, Boris; Kozak, Christine A; Kröger, Nicolaus; Stocking, Carol

    2014-06-10

    The compound immunodeficiencies in nonobese diabetic (NOD) inbred mice homozygous for the Prkdc(scid) and Il2rg(null) alleles (NSG mice) permit engraftment of a wide-range of primary human cells, enabling sophisticated modeling of human disease. In studies designed to define neoplastic stem cells of primary myelofibrosis (PMF), a myeloproliferative neoplasm characterized by profound disruption of the hematopoietic microenvironment, we observed a high frequency of acute myeloid leukemia (AML) in NSG mice. AML was of mouse origin, confined to PMF-xenografted mice, and contained multiple clonal integrations of ecotropic murine leukemia virus (E-MuLV). Significantly, MuLV replication was not only observed in diseased mice, but also in nontreated NSG controls. Furthermore, in addition to the single ecotropic endogenous retrovirus (eERV) located on chromosome 11 (Emv30) in the NOD genome, multiple de novo germ-line eERV integrations were observed in mice from each of four independent NSG mouse colonies. Analysis confirmed that E-MuLV originated from the Emv30 provirus and that recombination events were not necessary for virus replication or AML induction. Pathogenicity is thus likely attributable to PMF-mediated paracrine stimulation of mouse myeloid cells, which serve as targets for retroviral infection and transformation, as evidenced by integration into the Evi1 locus, a hotspot for retroviral-induced myeloid leukemia. This study thus corroborates a role of paracrine stimulation in PMF disease progression, underlines the importance of target cell type and numbers in MuLV-induced disease, and mandates awareness of replicating MuLV in NOD immunodeficient mice, which can significantly influence experimental results and their interpretation.

  10. Lower or Standard Dose Regorafenib in Treating Patients With Refractory Metastatic Colorectal Cancer

    Science.gov (United States)

    2018-03-22

    Colon Adenocarcinoma; Rectal Adenocarcinoma; 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. pO2 Fluctuation Pattern and Cycling Hypoxia in Human Cervical Carcinoma and Melanoma Xenografts

    International Nuclear Information System (INIS)

    Ellingsen, Christine; Øvrebø, Kirsti Marie; Galappathi, Kanthi; Mathiesen, Berit; Rofstad, Einar K.

    2012-01-01

    Purpose: Blood perfusion in tumors is spatially and temporally heterogeneous, resulting in local fluctuations in tissue oxygen tension (pO 2 ) and tissue regions showing cycling hypoxia. In this study, we investigated whether the pO 2 fluctuation pattern and the extent of cycling hypoxia differ between tumor types showing high (e.g., cervical carcinoma xenograft) and low (e.g., melanoma xenograft) fractions of connective tissue-associated blood vessels. Methods and Materials: Two cervical carcinoma lines (CK-160 and TS-415) and two melanoma lines (A-07 and R-18) transplanted into BALB/c nu/nu mice were included in the study. Tissue pO 2 was measured simultaneously in two positions in each tumor by using a two-channel OxyLite fiber-optic oxygen-sensing device. The extent of acute and chronic hypoxia was assessed by combining a radiobiological and a pimonidazole-based immunohistochemical assay of tumor hypoxia. Results: The proportion of tumor regions showing pO 2 fluctuations, the pO 2 fluctuation frequency in these regions, and the relative amplitude of the pO 2 fluctuations were significantly higher in the melanoma xenografts than in the cervical carcinoma xenografts. Cervical carcinoma and melanoma xenografts did not differ significantly in the fraction of acutely hypoxic cells or the fraction of chronically hypoxic cells. However, the ratio between fraction of acutely hypoxic cells and fraction of chronically hypoxic cells was significantly higher in melanoma than in cervical carcinoma xenografts. Conclusions: Temporal heterogeneity in blood flow and tissue pO 2 in tumors may depend on tumor histology. Connective tissue surrounding microvessels may stabilize blood flow and pO 2 and, thus, protect tumor tissue from cycling hypoxia.

  12. Dietary patterns and colorectal cancer

    OpenAIRE

    Tayyem, Reema F.; Bawadi, Hiba A.; Shehadah, Ihab; Agraib, Lana M.; AbuMweis, Suhad S.; Al-Jaberi, Tareq; Al-Nusairr, Majed; Bani-Hani, Kamal E.; Heath, Dennis D.

    2016-01-01

    Summary Background & aimsDietary pattern and lifestyle have been reported to be important risk factors in the development of colorectal cancer (CRC). However, the mechanism of action of dietary factors in CRC disease is unclear. The aim of this study is the examination of several dietary choices and their potential association with the risk of developing CRC. MethodsDietary data was collected from 220 subjects who were previously diagnosed with CRC, and 281 control subjects (matched by age, g...

  13. Tumor markers in colorectal cancer

    OpenAIRE

    Fernandes, Luís César [UNIFESP; Matos, Delcio [UNIFESP

    2002-01-01

    Colorectal cancer is a clinical entity of a persistent relevance in clinical practice and its early diagnosis is a determinant factor to obtain better therapeutic results. Tumor markers are helpful means for a better approach to individuals with such neoplasm. In the present review, the authors analyze the phases in which surgical-clinical treatment markers must be used: diagnosis, determination of tumor stage, establishment of prognosis and detection of recurrence. Current and future markers...

  14. Syncytin immunoreactivity in colorectal cancer

    DEFF Research Database (Denmark)

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

    2009-01-01

    monoclonal syncytin antibody we have assessed syncytin expression in a retrospective series of 140 colorectal cancer patients. Variable degrees of syncytin expression were detected in both colonic and rectal tumors and the prognostic impact of such expression was analysed with the Kaplan-Meier method...... 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....

  15. 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...

  16. Radiologic evaluation of colorectal cancer

    International Nuclear Information System (INIS)

    Lee, Young Joong; Kang, Hee Tae; Kim, Jong Deok; Rhee, Hak Song

    1984-01-01

    The incidence of colorectal cancer of Korea is much lower than that of Western countries, but has shown a tendency to a slight increase recently. Barium enema is the most valuable, noninvasive and inexpensive method available to evaluate the size, shape and site of colorectal cancer. The authors reviewed and radiologically classified barium enema studies of 232 cases of colorectal cancer from Aug. 1967 to July 1982 at Presbyterian Medical Center, Jeonju, Confirmed clinically, operatively and pathologically. The results were as follows; 1. The ratio of male and female was 1.3:1, and youngest was 13 year-old and the oldest 86 year-old. 2. The peak incidence occurred from 5th to 7th decades, accounting for 78% of all cases (181/232), and there was a relatively high incidence of the disease in patients below 30 years of age at 7.8% (18/232). 3. Rectum and rectosigmoid region are the most frequently involved regions (127/232:54.8%). 4. The positivity of barium enema examination was 4.0% (232/5807), and its accuracy was 96.5% (224/232). 5. The radiologic findings were classified into 4 groups, and they were annular encircling 62.9% (146/232). polypoid fungating 26.8% (62/232), infiltrating 8.6% (20/232), and primary ulcerating 1.7% (4/232) in order of frequency. 6. The linear length of the cancer ranged from 1.5 Cm to 15 Cm, and the average length was 5.5 Cm. 7. There was no statistical correlation between the length of lesion, the site, and the radiologic findings, and stages of the lesion (P:0.750-0.250). 8. The majority of colorectal cancers was adenocarcinoma (217/232:93.6%)

  17. 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

  18. MALIGNANCY IN LARGE COLORECTAL LESIONS

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Oliveira dos SANTOS

    2014-09-01

    Full Text Available Context The size of colorectal lesions, besides a risk factor for malignancy, is a predictor for deeper invasion Objectives To evaluate the malignancy of colorectal lesions ≥20 mm. Methods Between 2007 and 2011, 76 neoplasms ≥20 mm in 70 patients were analyzed Results The mean age of the patients was 67.4 years, and 41 were women. Mean lesion size was 24.7 mm ± 6.2 mm (range: 20 to 50 mm. Half of the neoplasms were polypoid and the other half were non-polypoid. Forty-two (55.3% lesions were located in the left colon, and 34 in the right colon. There was a high prevalence of III L (39.5% and IV (53.9% pit patterns. There were 72 adenomas and 4 adenocarcinomas. Malignancy was observed in 5.3% of the lesions. Thirty-three lesions presented advanced histology (adenomas with high-grade dysplasia or early adenocarcinoma, with no difference in morphology and site. Only one lesion (1.3% invaded the submucosa. Lesions larger than 30 mm had advanced histology (P = 0.001. The primary treatment was endoscopic resection, and invasive carcinoma was referred to surgery. Recurrence rate was 10.6%. Conclusions Large colorectal neoplasms showed a low rate of malignancy. Endoscopic treatment is an effective therapy for these lesions.

  19. Treatment of colorectal liver metastases

    Directory of Open Access Journals (Sweden)

    Ismaili Nabil

    2011-11-01

    Full Text Available Abstract Colorectal cancer (CRC is the third most common cancer in the word. Liver metastasis is the most common site of colorectal metastases. The prognosis of resectable colorectal liver metastases (CRLM was improved in the recent years with the consideration of chemotherapy and surgical resection as part of the multidisciplinary management of the disease; the current 5-year survival rates after resection of liver metastases are 25% to 40%. Resectable synchronous or metachronous liver metastases should be treated with perioperative chemotherapy based on three months of FOLFOX4 (5-fluorouracil [5FU], folinic acid [LV], and oxaliplatin chemotherapy before surgery and three months after surgery. In the case of primary surgery, pseudo-adjuvant chemotherapy for 6 months, based on 5FU/LV, FOLFOX4, XELOX (capecitabine and oxaliplatin or FOLFIRI (5FU/LV and irinotecan, should be indicated. In potentially resectable disease, primary chemotherapy based on more intensive regimens such as FOLFIRINOX (5FU/LV, irinotecan and oxaliplatin should be considered to enhance the chance of cure. The palliative chemotherapy based on FOLFIRI, or FOLFOX4/XELOX with or without targeted therapies, is the mainstay treatment of unresectable disease. This review would provide additional insight into the problem of optimal integration of chemotherapy and surgery in the management of CRLM.

  20. Long-term results of vaginal repairs with and without xenograft reinforcement

    DEFF Research Database (Denmark)

    Mouritsen, Lone; Kronschnabl, M.; Lose, G.

    2010-01-01

    The aim of this paper is to study if xenograft reinforcement of vaginal repair reduces recurrence of prolapse. Results 1-5 years after vaginal repair were studied in 41 cases with xenograft and in 82 matched controls without. Symptoms were evaluated by a validated questionnaire and anatomy...... in 3% of cases and 12% controls. None of the recurrence rates was significantly different for cases versus controls. No vaginal erosions were seen. Previous surgery was a significant risk factor with odds ratio 7.3 for another recurrence. Recurrence rates defined by POPQ plus symptoms were low compared...

  1. Long-term results of vaginal repairs with and without xenograft reinforcement

    DEFF Research Database (Denmark)

    Mouritsen, Lone; Kronschnabl, M.; Lose, G.

    2010-01-01

    INTRODUCTION AND HYPOTHESIS: The aim of this paper is to study if xenograft reinforcement of vaginal repair reduces recurrence of prolapse. METHODS: Results 1-5 years after vaginal repair were studied in 41 cases with xenograft and in 82 matched controls without. Symptoms were evaluated...... as POPQ > -1 plus symptoms revealed recurrence in 3% of cases and 12% controls. None of the recurrence rates was significantly different for cases versus controls. No vaginal erosions were seen. Previous surgery was a significant risk factor with odds ratio 7.3 for another recurrence. CONCLUSIONS...

  2. The HSP90 inhibitor 17-AAG exhibits potent antitumor activity for pheochromocytoma in a xenograft model.

    Science.gov (United States)

    Xu, Yunze; Zhu, Qi; Chen, Dongning; Shen, Zhoujun; Wang, Weiqing; Ning, Guang; Zhu, Yu

    2015-07-01

    This study aims to investigate the effect of heat shock protein 90 (HSP90) inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) in the malignant pheochromocytoma using a xenograft mouse model. Treatment with 17-AAG induced a marked reduction in the volume and weight of PC12 pheochromocytoma cell tumor xenografts in mice. Furthermore, 17-AAG also significantly inhibited the expression of HSP90 and its client proteins. Our results validated HSP90 as an important target in pheochromocytoma and provided rationale for the testing of HSP90 inhibitors as a promising therapeutic agent in the antitumor therapy of pheochromocytoma.

  3. Mesenchymal stem cell-based NK4 gene therapy in nude mice bearing gastric cancer xenografts

    Directory of Open Access Journals (Sweden)

    Zhu Y

    2014-12-01

    Full Text Available Yin Zhu,1,* Ming Cheng,2,* Zhen Yang,3 Chun-Yan Zeng,3 Jiang Chen,3 Yong Xie,3 Shi-Wen Luo,3 Kun-He Zhang,3 Shu-Feng Zhou,4 Nong-Hua Lu1,31Department of Gastroenterology, 2Department of Orthopedics, 3Institute of Digestive Disease, The First Affiliated Hospital of Nanchang University, Jiangxi, People’s Republic of China; 4Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA*These authors contributed equally to this workAbstract: Mesenchymal stem cells (MSCs have been recognized as promising delivery vehicles for gene therapy of tumors. Gastric cancer is the third leading cause of worldwide cancer mortality, and novel treatment modalities are urgently needed. NK4 is an antagonist of hepatocyte growth factor receptors (Met which are often aberrantly activated in gastric cancer and thus represent a useful candidate for targeted therapies. This study investigated MSC-delivered NK4 gene therapy in nude mice bearing gastric cancer xenografts. MSCs were transduced with lentiviral vectors carrying NK4 complementary DNA or enhanced green fluorescent protein (GFP. Such transduction did not change the phenotype of MSCs. Gastric cancer xenografts were established in BALB/C nude mice, and the mice were treated with phosphate-buffered saline (PBS, MSCs-GFP, Lenti-NK4, or MSCs-NK4. The tropism of MSCs toward gastric cancer cells was determined by an in vitro migration assay using MKN45 cells, GES-1 cells and human fibroblasts and their presence in tumor xenografts. Tumor growth, tumor cell apoptosis and intratumoral microvessel density of tumor tissue were measured in nude mice bearing gastric cancer xenografts treated with PBS, MSCs-GFP, Lenti-NK4, or MSCs-NK4 via tail vein injection. The results showed that MSCs migrated preferably to gastric cancer cells in vitro. Systemic MSCs-NK4 injection significantly suppressed the growth of gastric cancer xenografts. MSCs-NK4 migrated and accumulated in tumor

  4. Systems Support Mapping in Guiding Self-Management in Stage I-III Colorectal Cancer Survivors

    Science.gov (United States)

    2018-04-26

    Cancer Survivor; Stage I Colorectal Cancer AJCC v8; Stage II Colorectal Cancer AJCC v8; Stage IIA Colorectal Cancer AJCC v8; Stage IIB Colorectal Cancer AJCC v8; Stage IIC Colorectal Cancer AJCC v8; Stage III Colorectal Cancer AJCC v8; Stage IIIA Colorectal Cancer AJCC v8; Stage IIIB Colorectal Cancer AJCC v8; Stage IIIC Colorectal Cancer AJCC v8

  5. Colorectal choriocarcinoma in a patient with probable Lynch syndrome

    Directory of Open Access Journals (Sweden)

    Viktor Hendrik Koelzer

    2016-11-01

    Full Text Available Background: Personalized therapy of colorectal cancer (CRC is influenced by morphological, molecular and host-related factors. Here we report the comprehensive clinicopathological and molecular analysis of a pure extra-gestational colorectal choriocarcinoma in a patient with probable Lynch syndrome.Case presentation: A 61 year old female with history of gastric cancer at age 36 presented with a transmurally invasive tumor of the right hemicolon and liver metastasis. A right hemicolectomy was performed. Histopathological analysis showed a mixed trophoblastic and syncytiotrophoblastic differentiation, consistent with choriocarcinoma. Disease progression was rapid under oxaliplatin, capecitabine, irinotecan (XELOXIRI and bevacizumab. Molecular phenotyping identified loss of the mismatch-repair (MMR protein PMS2, microsatellite instability, a lack of MLH1 promoter methylation and lack of of BRAF mutation suggestive of Lynch-Syndrome. Targeted next generation sequencing revealed an Ataxia Telangiectasia Mutated (ATM p.P604S missense mutation. A bleomycin, etoposide and cisplatin (BEP treatment protocol targeting germ-cell neoplasia lead to disease remission and prolonged survival of 34 months.Conclusions: Comprehensive immunohistochemical and genetic testing is essential to identify uncommon cancers possibly related to Lynch syndrome. For rare tumors, personalized therapeutic approaches should take both molecular and morphological information into account.Key words: Colorectal cancer, choriocarcinoma, histopathology, prognostic factors, Lynch syndrome, microsatellite instability, ataxia telangiectasia mutated, molecular pathology, next generation sequencing, personalized medicine

  6. Cyclooxygenase-2 inhibitors in colorectal cancer prevention: point.

    Science.gov (United States)

    Arber, Nadir

    2008-08-01

    The limited success of current treatments for most advanced common malignancies highlights the importance of cancer prevention. Clinical trials on cyclooxygenase (COX) inhibitor drugs showed the potential of chemoprevention as a strategy for reducing cancer incidence, although not without associated side effects. The attractiveness of these drugs partly stems from an ability to engage multiple mechanisms of action by their potential to influence multiple components of the carcinogenesis pathway, from initiation to progression. There are two isoforms of the COX enzymes. COX-1 is constitutively expressed in normal tissues and serves as a "housekeeper" of mucosal integrity, whereas COX-2 is an immediate early response gene that is highly inducible by neoplastic and inflammatory stimuli. COX-2 is significantly overexpressed in colorectal neoplasms, making it an attractive therapeutic target. The drug market has been revolutionized by the development of preparations targeted selectively against COX-2, and a proof of concept has been achieved. Chemoprevention of colorectal cancer is already possible with celecoxib, but it is still not the ultimate drug of choice especially because of the cardiovascular risk associated with COX-2 inhibitors. Better patient selection and more effective and safer drugs are needed. Celecoxib is probably best used in a subset of individuals at moderate to high colorectal cancer risk and low risk of cardiovascular disease.

  7. 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....

  8. Clinical Outcomes of Colorectal Cancer in Kenya

    African Journals Online (AJOL)

    treatment and follow up were included. Patient ... and recurrence and the associated patient and disease ... The incidence of colorectal cancer (CRC) in the devel- ... therapy, disease stage and curative intent (table 3). ... through genetic and family analyses (4,6). ... Polite BN, Dignam JJ: A colorectal cancer model of health.

  9. Iatrogenic colorectal Kaposi sarcoma complicating a refractory ...

    African Journals Online (AJOL)

    Kaposi sarcoma is a mesenchymal tumor associated to a human herpes virus-8. It often occurs in human immunodeficiency virus-positive subjects. Colorectal localization is rare. We report the case of a colorectal Kaposi sarcoma complicating a refractory ulcerative colitis treated with surgery after the failure of ...

  10. 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

  11. Optimizing Outcomes of Colorectal Cancer Screening

    NARCIS (Netherlands)

    R.G.S. Meester (Reinier)

    2017-01-01

    markdownabstractColorectal cancer is a leading cause of cancer deaths. Screening for colorectal cancer is implemented in an increasing number of settings, but performance of programs is often suboptimal. In this thesis, advanced modeling, informed by empirical data, was used to identify areas for

  12. Pitfalls and Opportunities in Colorectal Cancer Screening

    NARCIS (Netherlands)

    P.G. van Putten (Paul)

    2013-01-01

    textabstractColorectal cancer (CRC) is the third most common cancer and the second leading cause of death from cancer in the Western world. Screening has been shown to reduce CRC incidence and mortality. The first evidence that colorectal cancer screening could effectively reduce mortality dates

  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. Vegetarianism, low meat consumption and the risk of colorectal cancer in a population based cohort study

    NARCIS (Netherlands)

    Gilsing, A.M.J.; Schouten, L.J.; Goldbohm, R.A.; Dagnelie, P.C.; Brandt, P.A. van den; Weijenberg, M.P.

    2015-01-01

    To study how a vegetarian or low meat diet influences the risk of colorectal cancer compared to a high meat diet, and to assess the explanatory role of factors associated with these diets. In the Netherlands Cohort Study – Meat Investigation Cohort (NLCS-MIC) (cohort of 10,210 individuals including

  15. Stool microbiome and metabolome differences between colorectal cancer patients and healthy adults

    Science.gov (United States)

    In this study we used stool profiling to identify intestinal bacteria and metabolites that are differentially represented in humans with colorectal cancer (CRC) compared to healthy controls to identify how microbial functions may influence CRC development. Stool samples were collected from healthy a...

  16. Educational level and risk of colorectal cancer in EPIC with specific reference to tumor location

    NARCIS (Netherlands)

    Leufkens, Anke M.; van Duijnhoven, Fränzel J. B.; Boshuizen, Hendriek C.; Siersema, Peter D.; Kunst, Anton E.; Mouw, Traci; Tjønneland, Anne; Olsen, Anja; Overvad, Kim; Boutron-Ruault, Marie-Christine; Clavel-Chapelon, Françoise; Morois, Sophie; Krogh, Vittorio; Tumino, Rosario; Panico, Salvatore; Polidoro, Silvia; Palli, Domenico; Kaaks, Rudolf; Teucher, Birgit; Pischon, Tobias; Trichopoulou, Antonia; Orfanos, Philippos; Goufa, Ioulia; Peeters, Petra H. M.; Skeie, Guri; Braaten, Tonje; Rodríguez, Laudina; Lujan-Barroso, Leila; Sánchez-Pérez, Maria-José; Navarro, Carmen; Barricarte, Aurelio; Zackrisson, Sophia; Almquist, Martin; Hallmans, Goran; Palmqvist, Richard; Tsilidis, Konstantinos K.; Khaw, Kay-Tee; Wareham, Nick; Gallo, Valentina; Jenab, Mazda; Riboli, Elio; Bueno-de-Mesquita, H. Bas

    2012-01-01

    Existing evidence is inconclusive on whether socioeconomic status (SES) and educational inequalities influence colorectal cancer (CRC) risk, and whether low or high SES/educational level is associated with developing CRC. The aim of our study was to investigate the relationship between educational

  17. Spatial variation in stage distribution in colorectal cancer in the Netherlands

    NARCIS (Netherlands)

    Elferink, M.A.G.; Pukkala, E.; Klaase, J.M.; Siesling, Sabine

    2012-01-01

    Background: In the Netherlands the incidence of colorectal cancer has increased, mainly in the eastern part of the country. Patient delay due to unawareness or ignorance of symptoms and differences in use of diagnostic tools could have influence on the stage distribution. The aim of this study was

  18. Genetic predictors for the response to therapy in colorectal cancer cells

    NARCIS (Netherlands)

    de Bruijn, M.T.

    2011-01-01

    The general goal of this thesis is to create a better insight into the genes and signaling proteins that influence the response of colorectal cancer cells to MEK-targeted therapy and chemotherapy (5-FU and oxaliplatin). In chapter 2 of this thesis we set out to explore the mechanisms of resistance

  19. PDX-MI: Minimal Information for Patient-Derived Tumor Xenograft Models

    NARCIS (Netherlands)

    Meehan, Terrence F.; Conte, Nathalie; Goldstein, Theodore; Inghirami, Giorgio; Murakami, Mark A.; Brabetz, Sebastian; Gu, Zhiping; Wiser, Jeffrey A.; Dunn, Patrick; Begley, Dale A.; Krupke, Debra M.; Bertotti, Andrea; Bruna, Alejandra; Brush, Matthew H.; Byrne, Annette T.; Caldas, Carlos; Christie, Amanda L.; Clark, Dominic A.; Dowst, Heidi; Dry, Jonathan R.; Doroshow, James H.; Duchamp, Olivier; Evrard, Yvonne A.; Ferretti, Stephane; Frese, Kristopher K.; Goodwin, Neal C.; Greenawalt, Danielle; Haendel, Melissa A.; Hermans, Els; Houghton, Peter J.; Jonkers, Jos; Kemper, Kristel; Khor, Tin O.; Lewis, Michael T.; Lloyd, K. C. Kent; Mason, Jeremy; Medico, Enzo; Neuhauser, Steven B.; Olson, James M.; Peeper, Daniel S.; Rueda, Oscar M.; Seong, Je Kyung; Trusolino, Livio; Vinolo, Emilie; Wechsler-Reya, Robert J.; Weinstock, David M.; Welm, Alana; Weroha, S. John; Amant, Frédéric; Pfister, Stefan M.; Kool, Marcel; Parkinson, Helen; Butte, Atul J.; Bult, Carol J.

    2017-01-01

    Patient-derived tumor xenograft (PDX) mouse models have emerged as an important oncology research platform to study tumor evolution, mechanisms of drug response and resistance, and tailoring chemotherapeutic approaches for individual patients. The lack of robust standards for reporting on PDX models

  20. Interrogating open issues in cancer precision medicine with patient-derived xenografts

    NARCIS (Netherlands)

    Byrne, Annette T; Alférez, Denis G; Amant, Frédéric; Annibali, Daniela; Arribas, Joaquín; Biankin, Andrew V; Bruna, Alejandra; Budinská, Eva; Caldas, Carlos; Chang, David K; Clarke, Robert B; Clevers, Hans; Coukos, George; Dangles-Marie, Virginie; Eckhardt, S Gail; Gonzalez-Suarez, Eva; Hermans, Els; Hidalgo, Manuel; Jarzabek, Monika A; de Jong, Steven; Jonkers, Jos; Kemper, Kristel; Lanfrancone, Luisa; Mælandsmo, Gunhild Mari; Marangoni, Elisabetta; Marine, Jean-Christophe; Medico, Enzo; Norum, Jens Henrik; Palmer, Héctor G; Peeper, Daniel S; Pelicci, Pier Giuseppe; Piris-Gimenez, Alejandro; Roman-Roman, Sergio; Rueda, Oscar M; Seoane, Joan; Serra, Violeta; Soucek, Laura; Vanhecke, Dominique; Villanueva, Alberto; Vinolo, Emilie; Bertotti, Andrea; Trusolino, Livio

    Patient-derived xenografts (PDXs) have emerged as an important platform to elucidate new treatments and biomarkers in oncology. PDX models are used to address clinically relevant questions, including the contribution of tumour heterogeneity to therapeutic responsiveness, the patterns of cancer

  1. Interrogating open issues in cancer precision medicine with patient-derived xenografts

    NARCIS (Netherlands)

    Byrne, Annette T.; Alférez, Denis G.; Amant, Frédéric; Annibali, Daniela; Arribas, Joaquín; Biankin, Andrew V.; Bruna, Alejandra; Budinská, Eva; Caldas, Carlos; Chang, David K.; Clarke, Robert B.; Clevers, Hans; Coukos, George; Dangles-Marie, Virginie; Eckhardt, S. Gail; Gonzalez-Suarez, Eva; Hermans, Els; Hidalgo, Manuel; Jarzabek, Monika A.; de Jong, Steven; Jonkers, Jos; Kemper, Kristel; Lanfrancone, Luisa; Mælandsmo, Gunhild Mari; Marangoni, Elisabetta; Marine, Jean-Christophe; Medico, Enzo; Norum, Jens Henrik; Palmer, Héctor G.; Peeper, Daniel S.; Pelicci, Pier Giuseppe; Piris-Gimenez, Alejandro; Roman-Roman, Sergio; Rueda, Oscar M.; Seoane, Joan; Serra, Violeta; Soucek, Laura; Vanhecke, Dominique; Villanueva, Alberto; Vinolo, Emilie; Bertotti, Andrea; Trusolino, Livio

    2017-01-01

    Patient-derived xenografts (PDXs) have emerged as an important platform to elucidate new treatments and biomarkers in oncology. PDX models are used to address clinically relevant questions, including the contribution of tumour heterogeneity to therapeutic responsiveness, the patterns of cancer

  2. Patient-Derived Xenograft Models : An Emerging Platform for Translational Cancer Research

    NARCIS (Netherlands)

    Hidalgo, Manuel; Amant, Frederic; Biankin, Andrew V.; Budinska, Eva; Byrne, Annette T.; Caldas, Carlos; Clarke, Robert B.; de Jong, Steven; Jonkers, Jos; Maelandsmo, Gunhild Mari; Roman-Roman, Sergio; Seoane, Joan; Trusolino, Livio; Villanueva, Alberto

    Recently, there has been an increasing interest in the development and characterization of patient-derived tumor xenograft (PDX) models for cancer research. PDX models mostly retain the principal histologic and genetic characteristics of their donor tumor and remain stable across passages. These

  3. The Public Repository of Xenografts enables discovery and randomized phase II-like trials in mice

    NARCIS (Netherlands)

    E.C. Townsend (Elizabeth); M.A. Murakami (Mark); A. Christodoulou (Alexandra); A.L. Christie (Amanda); J. Köster (Johannes); T.A. DeSouza (Tiffany); E.A. Morgan (Elizabeth); S.P. Kallgren (Scott); H. Liu (Huiyun); S.-C. Wu (Shuo-Chieh); O. Plana (Olivia); J. Montero (Joan); K.E. Stevenson (Kristen); P. Rao (Prakash); R. Vadhi (Raga); M. Andreeff (Michael); P. Armand (Philippe); K.K. Ballen (Karen); P. Barzaghi-Rinaudo (Patrizia); S. Cahill (Sarah); R.A. Clark (Rachael); V.G. Cooke (Vesselina); M.S. Davids (Matthew); D.J. DeAngelo (Daniel); D.M. Dorfman; H. Eaton (Hilary); B.L. Ebert (Benjamin); J. Etchin (Julia); B. Firestone (Brant); D.C. Fisher (David); A.S. Freedman (Arnold); I.A. Galinsky, () (Ilene); H. Gao (Hui); J.S. Garcia, () (Jacqueline); F. Gamache-Ottou (Francine); T.A. Graubert (Timothy); A. Gutierrez (Alejandro); E. Halilovic (Ensar); M.H. Harris (Marian); Z.T. Herbert (Zachary); S.M. Horwitz (Steven); G. Inghirami (Giorgio); A.M. Intlekofer (Andrew); M. Ito (Moriko); S. Izraeli (Shai); E.D. Jacobsen (Eric); C.A. Jacobson (Caron); S. Jeay (Sébastien); I. Jeremias (Irmela); M.A. Kelliher (Michelle); R. Koch (Raphael); M. Konopleva (Marina); N. Kopp (Nadja); S.M. Kornblau (Steven); A.L. Kung (Andrew); T.S. Kupper (Thomas); N.R. LeBoeuf (Nicole); A.S. LaCasce (Ann); E. Lees (Emma); L.S. Li (Loretta); A.T. Look (Thomas); M. Murakami (Masato); M. Muschen (Markus); D. Neuberg (Donna); S.Y. Ng (Samuel); O.O. Odejde (Oreofe); S.H. Orkin (Stuart); R.R. Paquette (Rachel); A.A. Place (Andrew); J.E. Roderick (Justine); J.A. Ryan (Jeremy); S.E. Sallan (Stephen); B. Shoji (Brent); L.B. Silverman (Lewis); R.J. Soiffer (Robert); D.P. Steensma (David); K. Stegmaier (Kimberley); R.M. Stone (Richard); J. Tamburini (Jerome); A.R. Thorner (Aaron); P. van Hummelen (Paul); M. Wadleigh (Martha); M. Wiesmann (Marion); A.P. Weng (Andrew); J.U. Wuerthner (Jens); D.A. Williams (David); B.M. Wollison (Bruce); A.A. Lane (Andrew); A. Letai (Anthony); M.M. Bertagnolli (Monica); J. Ritz (Jerome); M. Brown (Myles); H. Long (Henry); J.C. Aster (Jon); M.A. Shipp (Margaret); J.D. Griffin (James); D.M. Weinstock (David)

    2016-01-01

    textabstractMore than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address

  4. Anti-EGFR therapy radiosensitizes human lung adenocarcinoma xenograft in nude mouse

    International Nuclear Information System (INIS)

    Wang Hui; Li Tianran; Tian Jiahe; Qu Baolin; Zhu Hui

    2008-01-01

    Objective: To investigate the effect of Gefitinib on radiosensitivity of human lung adenocarcinoma xenograft in nude mouse. Methods: Human lung adenocarcinoma cell line A549 was used to establish nude mouse xenograft tumor model. The mice were derided into 4 groups: control, irradiation alone, Gefinitib alone and radiation combined with Genifitib. Radiation schedule was 3 fractions of 5 Gy, once daily. Gefitinib was daily administered by gavage at 100 mg/(kg·day -1 ) for 14 days. In the combination group, radiotherapy was performed 2 hours after Gefitinib administration. Tumor diameter was measured every other day. Percentage of tumor growth inhibition, growth delay time and regrowth delay time were evaluated. Results: For A549 xenografts in radiation alone, gefitinib alone and combination therapy groups, the percentage of tumor growth inhibition was 22.7%, 12.4% and 38.2%, respectively (F=25.75, P=0.000). Tumor growth delay time was 6.0, 7.8 and 21.6 days, respectively (F=70.49, P=0.000). Tumor regrowth delay time in combination therapy and irradiation alone groups was 23.4 and 10.2 days. (F=174.24, P= 0.000). Sensitizing enhancement ratio of combination group was 1.5 in growth and 1.7 in regrowth. Conclusions: Anti-EGFR therapy enhances the radiosensitivity of human lung adenocarcinoma xenograft in nude mouse. (authors)

  5. Noninvasive detection of temozolomide in brain tumor xenografts by magnetic resonance spectroscopy

    DEFF Research Database (Denmark)

    Kato, Y.; Holm, David Alberg; Okollie, B.

    2010-01-01

    demonstrate partial breakdown of the BBB/BTB and good vascularization in U87MG xenografts. A [C-13] TMZ peak was detected at 3.9 ppm by HMQC from a selected volume of about 0.15 cm(3) within the brain tumor with HMQC pulse sequences. This study clearly demonstrates the noninvasive detection of [C-13]TMZ...

  6. Validation of a mouse xenograft model system for gene expression analysis of human acute lymphoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Francis Richard W

    2010-04-01

    Full Text Available Abstract Background Pre-clinical models that effectively recapitulate human disease are critical for expanding our knowledge of cancer biology and drug resistance mechanisms. For haematological malignancies, the non-obese diabetic/severe combined immunodeficient (NOD/SCID mouse is one of the most successful models to study paediatric acute lymphoblastic leukaemia (ALL. However, for this model to be effective for studying engraftment and therapy responses at the whole genome level, careful molecular characterisation is essential. Results Here, we sought to validate species-specific gene expression profiling in the high engraftment continuous ALL NOD/SCID xenograft. Using the human Affymetrix whole transcript platform we analysed transcriptional profiles from engrafted tissues without prior cell separation of mouse cells and found it to return highly reproducible profiles in xenografts from individual mice. The model was further tested with experimental mixtures of human and mouse cells, demonstrating that the presence of mouse cells does not significantly skew expression profiles when xenografts contain 90% or more human cells. In addition, we present a novel in silico and experimental masking approach to identify probes and transcript clusters susceptible to cross-species hybridisation. Conclusions We demonstrate species-specific transcriptional profiles can be obtained from xenografts when high levels of engraftment are achieved or with the application of transcript cluster masks. Importantly, this masking approach can be applied and adapted to other xenograft models where human tissue infiltration is lower. This model provides a powerful platform for identifying genes and pathways associated with ALL disease progression and response to therapy in vivo.

  7. Regorafenib inhibits colorectal tumor growth through PUMA-mediated apoptosis

    Science.gov (United States)

    Chen, Dongshi; Wei, Liang; Yu, Jian; Zhang, Lin

    2014-01-01

    Purpose Regorafenib, a multi-kinase inhibitor targeting the Ras/Raf/MEK/ERK pathway, has recently been approved for the treatment of metastatic colorectal cancer (CRC). However, the mechanisms of action of regorafenib in CRC cells have been unclear. We investigated how regorafenib suppresses CRC cell growth and potentiates effects of other chemotherapeutic drugs. Experimental Design We determined whether and how regorafenib induces the expression of PUMA, a p53 target and a critical mediator of apoptosis in CRC cells. We also investigated whether PUMA is necessary for the killing and chemosensitization effects of regorafenib in CRC cells. Furthermore, xenograft tumors were used to test if PUMA mediates the in vivo antitumor, antiangiogenic and chemosensitization effects of regorafenib. Results We found that regorafenib treatment induces PUMA in CRC cells irrespective of p53 status through the NF-κB pathway following ERK inhibition and glycogen synthase kinase 3β (GSK3β) activation. Upregulation of PUMA is correlated with apoptosis induction in different CRC cell lines. PUMA is necessary for regorafenib-induced apoptosis in CRC cells. Chemosensitization by regorafenib is mediated by enhanced PUMA induction through different pathways. Furthermore, deficiency in PUMA abrogates the in vivo antitumor, antiangiogenic and chemosensitization effects of regorafenib. Conclusions Our results demonstrate a key role of PUMA in mediating the anticancer effects of regorafenib in CRC cells. They suggest that PUMA induction can be used as an indicator of regorafenib sensitivity, and also provide a rationale for manipulating the apoptotic machinery to improve the therapeutic efficacy of regorafenib and other targeted drugs. PMID:24763611

  8. SHP-1 is a target of regorafenib in colorectal cancer

    Science.gov (United States)

    Lin, Hang; Hung, Man-Hsin; Chen, Yen-Lin; Huang, Jui-Wen; Tai, Wei-Tien; Yu, Hui-Chuan; Chen, Kuen-Feng

    2014-01-01

    Regorafenib is an inhibitor of multiple protein kinases which exerts antitumor and antimetastatic activities in metastatic colorectal cancer (CRC). SH2 domain-containing phosphatase 1 (SHP-1) is reported to have tumor suppressive potential because it acts as a negative regulator of p-STAT3Tyr705 signaling. However, little is known about the mechanism regarding regorafenib affects SHP-1 tyrosine phosphatase activity and leads to apoptosis and tumor suppression in CRC. Here, we found that regorafenib triggered apoptotic cell death and significantly enhanced SHP-1 activity, which dramatically decreased the phosphorylated form of STAT3 at Tyr705 (p-STAT3Tyr705). Importantly, regorafenib augmented SHP-1 activity by direct disruption of the association between N-SH2 and catalytic PTP domain of SHP-1. Deletion of the N-SH2 domain (dN1) or point mutation (D61A) of SHP-1 blocked the effect of regorafenib-induced SHP-1 activity, growth inhibition and a decrease of p-STAT3Tyr705 expression, suggesting that regorafenib triggers a conformational change in SHP-1 by relieving its autoinhibition. In vivo assay showed that regorafenib significantly inhibited xenograft growth and decreased p-STAT3Tyr705 expression but induced higher SHP-1 activity. Collectively, regorafenib is a novel SHP-1 agonist exerts superior anti-tumor effects by enhancing SHP-1 activity that directly targets p-STAT3Tyr705. Small molecule-enhancement of SHP-1 activity may be a promising therapeutic approach for CRC treatment. PMID:25071018

  9. Knockdown of Uba2 inhibits colorectal cancer cell invasion and migration through downregulation of the Wnt/β-catenin signaling pathway.

    Science.gov (United States)

    Cheng, Hongjing; Sun, Xun; Li, Ji; He, Ping; Liu, Wanqi; Meng, Xiangwei

    2018-05-10

    Colorectal cancer is a serious threat to human health, and has a high mortality rate. There is currently no effective therapy for end-stage colorectal cancer. In recent years, molecular targeted therapy has received increasing attention for cancer treatment. In particular, the role of Uba2, a vital component of SUMO-activating enzyme, has been highlighted, which plays important roles in the progression of certain cancers; however, its role in colorectal cancer remains unclear. Accordingly, the aim of this study was to evaluate the relationship between Uba2 and colorectal cancer. Uba2 expression was knocked down in two colorectal cancer cell lines, and gene microarray analysis was conducted, followed by proliferation, migration, and invasion assays. Uba2 knockdown influenced the expression of several genes, and significantly inhibited the proliferation, migration, and invasion of cancer cells. To determine the underlying mechanism, the expression of related signaling pathways and molecules was evaluated in the knockdown cell lines. Overall, the results suggest that Uba2 participates in the progression, invasion, and metastasis of colorectal cancer, and the possible mechanism is via regulating the Wnt signaling pathway and enhancing epithelial-mesenchymal transition behaviors of colorectal cancer cells. Therefore, Uba2 is expected to be an important oncoprotein and potential therapeutic target in colorectal cancer. © 2018 Wiley Periodicals, Inc.

  10. Dietary patterns and colorectal cancer.

    Science.gov (United States)

    Tayyem, Reema F; Bawadi, Hiba A; Shehadah, Ihab; Agraib, Lana M; AbuMweis, Suhad S; Al-Jaberi, Tareq; Al-Nusairr, Majed; Bani-Hani, Kamal E; Heath, Dennis D

    2017-06-01

    Dietary pattern and lifestyle have been reported to be important risk factors in the development of colorectal cancer (CRC). However, the mechanism of action of dietary factors in CRC disease is unclear. The aim of this study is the examination of several dietary choices and their potential association with the risk of developing CRC. Dietary data was collected from 220 subjects who were previously diagnosed with CRC, and 281 control subjects (matched by age, gender, occupation and marital status). The data was collected between January 2010 and December 2012, using interview-based questionnaires. Multivariate logistic regression was used to estimate the relationship between dietary choices and risk of developing colorectal cancer. Factor analysis revealed three major dietary patterns. The first pattern we identified as the "Healthy Pattern", the second was identified as "High Sugar/High Tea Pattern" and the third as "Western Pattern". In the Healthy Pattern group we found a 10.54% variation in food intake, while the intake variation was 11.64% in the Western Pattern. After adjusting for confounding factors, the Western Pattern food choice was found to be significantly associated with an increased risk of developing CRC (OR = 1.88; 95% CI = 1.12-3.16). The results for the Healthy and High-Sugar/High Tea Patterns showed a decrease, but the statistic was not significant for the risk of CRC development. The Western Pattern of dietary choice was directly associated with CRC. The association between the dietary food choice in the Healthy and High-Sugar/High Tea Patterns and colorectal cancer needs further study in our Jordanian population. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  11. Malnutrition In Patients With Colorectal Carcinoma (Oncologist's Point Of View)

    International Nuclear Information System (INIS)

    Zanova, M.

    2008-01-01

    Colorectal cancer is a worldwide health, social and economic problem. The incidence of malnutrition in patients with colorectal cancer is stated as 54 - 60 %. Primary cachexia is caused by hormonal, metabolic and energetic abnormalities; secondary cachexia is a consequence of functional and anatomic damage to digestive apparatus resulting from a tumor itself or its treatment. Colorectal carcinoma treatment is a complex process involving surgery, radiotherapy and cytostatic treatment. Each treatment modality also brings desirable and undesirable effects and influences patient's nutritional status. Malnutrition worsens patient's overall chances of successful treatment; therefore nutritional support aims to increase his/her anti-infection and antitumor immunity by means of mineral and water industry adjustment as well as by energetic stabilization. (author)

  12. Prospective study of dietary patterns and colorectal cancer among Singapore Chinese.

    Science.gov (United States)

    Butler, L M; Wang, R; Koh, W-P; Yu, M C

    2008-11-04

    An influence of Western diet and lifestyle factors observed among Singapore Chinese may contribute to the population's marked rise in colorectal cancer incidence over the past two decades. Thus far, however, there is little evidence for individual nutrients and foods as major contributing factors in this population. We evaluated whether patterns of food intake were associated with colorectal cancer in a population-based cohort of 61,321 Singapore Chinese that was established in 1993-98. Two dietary patterns, meat-dim sum and vegetable-fruit-soy, were previously identified by principal components analysis using baseline dietary data from a validated 165-item food frequency questionnaire. As of 31 December 2005, 961 incident colorectal cancer cases were diagnosed. Proportional hazards regression was used to calculate adjusted hazard ratios. Using nearly 10 years of follow-up data, we observed no association with either the meat-dim sum or vegetable-fruit-soy pattern for colorectal cancer. In conclusion, neither individual nutrients or foods nor dietary patterns appear to explain the rise in colorectal cancer among Singapore Chinese population.

  13. Lactobacillus salivarius Ren prevent the early colorectal carcinogenesis in 1, 2-dimethylhydrazine-induced rat model.

    Science.gov (United States)

    Zhu, J; Zhu, C; Ge, S; Zhang, M; Jiang, L; Cui, J; Ren, F

    2014-07-01

    The objective of this study was to investigate the impact of Lactobacillus salivarius Ren (LS) on modulating colonic micro flora structure and influencing host colonic health in a rat model with colorectal precancerous lesions. Male F344 rats were injected with 1, 2-dimethylhydrazine (DMH) and treated with LS of two doses (5 × 10(8) and 1 × 10(10) CFU kg(-1) body weight) for 15 weeks. The colonic microflora profiles, luminal metabolites, epithelial proliferation and precancerous lesions [aberrant crypt foci (ACF)] were determined. A distinct segregation of colonic microflora structures was observed in LS-treated group. The abundance of one Prevotella-related strain was increased, and the abundance of one Bacillus-related strain was decreased by LS treatment. These changes were accompanied by increased short-chain fatty acid levels and decreased azoreductase activity. LS treatment also reduced the number of ACF by c. 40% and suppressed epithelial proliferation. Lactobacillus salivarius Ren improved the colonic microflora structures and the luminal metabolisms in addition preventing the early colorectal carcinogenesis in DMH-induced rat model. Colonic microflora is an important factor in colorectal carcinogenesis. Modulating the structural shifts of microflora may provide a novel option for preventing colorectal carcinogenesis. This study suggested a potential probiotic-based approach to modulate the intestinal microflora in the prevention of colorectal carcinogenesis. © 2014 The Society for Applied Microbiology.

  14. Variant alleles of the CYP1B1 gene are associated with colorectal cancer susceptibility

    International Nuclear Information System (INIS)

    Trubicka, Joanna; Byrski, Tomasz; Gronwald, Jacek; Złowocka, Elżbieta; Kładny, Józef; Banaszkiewicz, Zbigniew; Wiśniowski, Rafał; Kowalska, Elżbieta; Lubinski, Jan; Scott, Rodney J; Grabowska-Kłujszo, Ewa; Suchy, Janina; Masojć, Bartłomiej; Serrano-Fernandez, Pablo; Kurzawski, Grzegorz; Cybulski, Cezary; Górski, Bohdan; Huzarski, Tomasz

    2010-01-01

    CYP1B1 is a P450 enzyme which is involved in the activation of pro-carcinogens to carcinogens as well as sex hormone metabolism. Because differences in the activity of the enzyme have been correlated with variant alleles of single nucleotide polymorphisms (SNPs), it represents an attractive candidate gene for studies into colorectal cancer susceptibility. We genotyped 597 cancer patients and 597controls for three CYP1B1 SNPs, which have previously been shown to be associated with altered enzymatic activity. Using the three SNPs, eight different haplotypes were constructed. The haplotype frequencies were estimated in cases and controls and then compared. The odds ratio for each tumour type, associated with each haplotype was estimated, with reference to the most common haplotype observed in the controls. The three SNPs rs10012, rs1056827 and rs1056836 alone did not provide any significant evidence of association with colorectal cancer risk. Haplotypes of rs1056827 and rs10012 or rs1056827 and rs1056836 revealed an association with colorectal cancer which was significantly stronger in the homozygous carriers. One haplotype was under represented in the colorectal cancer patient group compared to the control population suggesting a protective effect. Genetic variants within the CYP1B1 that are associated with altered function appear to influence susceptibility to a colorectal cancer in Poland. Three haplotypes were associated with altered cancer risk; one conferred protection and two were associated with an increased risk of disease. These observations should be confirmed in other populations

  15. Epidemiological and Experimental Studies: The Role of Metformin on Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Ratih D. Yudhani

    2016-12-01

    Full Text Available GLOBOCAN data in 2012 showed colorectal cancer was the third leading cancer worldwide. In Indonesia, based on WHO data in 2014, colorectal cancer was the second common cancer ini men and third cancer in women. Epidemiological studies showed that diabetes mellitus have a correlation with the incidence of cancer and increase colorectal cancer risk by 30%. Some of epidemiological study showed that metformin therapy in diabetes patient reduce the risk of cancer incidence. It supported by experimental study which showed that metformin inhibit the growth and proliferation of cancer cells by influence the AMPK/mTOR pathway as a main role. The method was literature review based on publication at Pubmed, Scopus, and Google Scholar with keywords “metformin, colorectal cancer”, “metformin, colon cancer”, without index factor limitation in free journal and paid journal. The aim of this review is to give a new insight of metformin activity as anti-cancer and its potential for both preventif and adjuvant cancer therapy, especially for colorectal cancer.

  16. Update on Sporadic Colorectal Cancer Genetics.

    Science.gov (United States)

    Hardiman, Karin M

    2018-05-01

    Our understanding of the genetics of colorectal cancer has changed dramatically over recent years. Colorectal cancer can be classified in multiple different ways. Along with the advent of whole-exome sequencing, we have gained an understanding of the scale of the genetic changes found in sporadic colorectal cancer. We now know that there are multiple pathways that are commonly involved in the evolution of colorectal cancer including Wnt/β-catenin, RAS, EGFR, and PIK3 kinase. Another recent leap in our understanding of colorectal cancer genetics is the recognition that many, if not all tumors, are actually genetically heterogeneous within individual tumors and also between tumors. Recent research has revealed the prognostic and possibly therapeutic implications of various specific mutations, including specific mutations in BRAF and KRAS . There is increasing interest in the use of mutation testing for screening and surveillance through stool and circulating DNA testing. Recent advances in translational research in colorectal cancer genetics are dramatically changing our understanding of colorectal cancer and will likely change therapy and surveillance in the near future.

  17. Perceived religiousness is protective for colorectal cancer: data from the Melbourne Colorectal Cancer Study.

    OpenAIRE

    Kune, G A; Kune, S; Watson, L F

    1993-01-01

    The perceived or self-reported degree of 'religiousness' was obtained by interview from 715 colorectal cancer patients and 727 age/sex matched community controls, as part of a large, comprehensive population-based study of colorectal cancer incidence, aetiology and survival (The Melbourne Colorectal Cancer Study) conducted in Melbourne, Australia. Self-reported or perceived 'religiousness', as defined in the study, was a statistically significant protective factor [relative risk (RR) = 0.70, ...

  18. Management of colorectal cancer and diabetes.

    Science.gov (United States)

    Yao, Caroline; Nash, Guy F; Hickish, Tamas

    2014-03-01

    Colorectal cancer is associated with diabetes mellitus and both of these common conditions are often managed together by a surgeon. The surgical focus is usually upon cancer treatment rather than diabetes management. The relationship between colorectal cancer and diabetes is a complex one and can raise problems in both diagnosis and the management of patients with both conditions. This literature review explores the relationship between diabetes, diabetic treatment and colorectal cancer and addresses the issues that arise in diagnosing and treating this patient group. By highlighting these difficulties, this review aims to improve understanding and to provide clearer insight into both surgical and non-surgical management.

  19. Uptake of radiolabeled anti-CEA antibodies in human colorectal primary tumors as a function of tumor mass

    International Nuclear Information System (INIS)

    Williams, L.E.; Bares, R.B.; Buell, U.; Fass, J.; Schumpelick, V.; Hauptmann, S.

    1993-01-01

    An inverse correlation has been demonstrated between tumor uptake (u, in units of % injected dose/kg) of monoclonal antibody (Mab) and tumor mass (m, in units of g) for colorectal carcinoma in a series of 19 consecutive patients. The correlation (ρ=-0.510), developed using surgical samples was of the form u=ab b and was significant at the 2% level of confidence. All tumors were positive for carcinoembryonic antigen (CEA) and the radiopharmaceutical was in iodine-131 labeled anti-CEA Mab. Such correlations have been predicted earlier from murine and rat tumor uptake data. The slope parameter (b) was -0.362, a number consistent with the previous value (-0.382) found in anti-CEA experiments in mice bearing human xenograft LS174T tumors. (orig.)

  20. Confocal Endomicroscopy of Colorectal Polyps

    Directory of Open Access Journals (Sweden)

    Vivian M. Ussui

    2012-01-01

    Full Text Available Confocal laser endomicroscopy (CLE is one of several novel methods that provide real-time, high-resolution imaging at a micron scale via endoscopes. CLE has the potential to be a disruptive technology in that it can change the current algorithms that depend on biopsy to perform surveillance of high-risk conditions. Furthermore, it allows on-table decision making that has the potential to guide therapy in real time and reduce the need for repeated procedures. CLE and related technologies are often termed “virtual biopsy” as they simulate the images seen in traditional histology. However, the imaging of living tissue allows more than just pragmatic convenience; it also allows imaging of living tissue such as active capillary circulation, cellular death, and vascular and endothelial translocation, thus extending beyond what is capable in traditional biopsy. Immediate potential applications of CLE are to guide biopsy sampling in Barrett's esophagus and inflammatory bowel disease surveillance, evaluation of colorectal polyps, and intraductal imaging of the pancreas and bile duct. Data on these applications is rapidly emerging, and more is needed to clearly demonstrate the optimal applications of CLE. In this paper, we will focus on the role of CLE as applied to colorectal polyps detected during colonoscopy.

  1. Mediterranean Diet: Prevention of Colorectal Cancer.

    Science.gov (United States)

    Donovan, Micah G; Selmin, Ornella I; Doetschman, Tom C; Romagnolo, Donato F

    2017-01-01

    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.

  2. Mediterranean Diet: Prevention of Colorectal Cancer

    Science.gov (United States)

    Donovan, Micah G.; Selmin, Ornella I.; Doetschman, Tom C.; Romagnolo, Donato F.

    2017-01-01

    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. PMID:29259973

  3. 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.

  4. EGFR gene overexpression retained in an invasive xenograft model by solid orthotopic transplantation of human glioblastoma multiforme into nude mice.

    Science.gov (United States)

    Yi, Diao; Hua, Tian Xin; Lin, Huang Yan

    2011-03-01

    Orthotopic xenograft animal model from human glioblastoma multiforme (GBM) cell lines often do not recapitulate an extremely important aspect of invasive growth and epidermal growth factor receptor (EGFR) gene overexpression of human GBM. We developed an orthotopic xenograft model by solid transplantation of human GBM into the brain of nude mouse. The orthotopic xenografts sharing the same histopathological features with their original human GBMs were highly invasive and retained the overexpression of EGFR gene. The murine orthotopic GBM models constitute a valuable in vivo system for preclinical studies to test novel therapies for human GBM.

  5. Halofuginone suppresses growth of human uterine leiomyoma cells in a mouse xenograft model.

    Science.gov (United States)

    Koohestani, Faezeh; Qiang, Wenan; MacNeill, Amy L; Druschitz, Stacy A; Serna, Vanida A; Adur, Malavika; Kurita, Takeshi; Nowak, Romana A

    2016-07-01

    Does halofuginone (HF) inhibit the growth of human uterine leiomyoma cells in a mouse xenograft model? HF suppresses the growth of human uterine leiomyoma cells in a mouse xenograft model through inhibiting cell proliferation and inducing apoptosis. Uterine leiomyomas are the most common benign tumors of the female reproductive tract. HF can suppress the growth of human uterine leiomyoma cells in vitro. The mouse xenograft model reflects the characteristics of human leiomyomas. Primary leiomyoma smooth muscle cells from eight patients were xenografted under the renal capsule of adult, ovariectomized NOD-scid IL2Rγ(null) mice (NSG). Mice were treated with two different doses of HF or vehicle for 4 weeks with six to eight mice per group. Mouse body weight measurements and immunohistochemical analysis of body organs were carried out to assess the safety of HF treatment. Xenografted tumors were measured and analyzed for cellular and molecular changes induced by HF. Ovarian steroid hormone receptors were evaluated for possible modulation by HF. Treatment of mice carrying human UL xenografts with HF at 0.25 or 0.50 mg/kg body weight for 4 weeks resulted in a 35-40% (P leiomyoma cells in an in vivo model, HF was administered to mice whose tolerance and metabolism of the drug may differ from that in humans. Also, the longer term effects of HF treatment are yet unclear. The results of this study showing the effectiveness of HF in reducing UL tumor growth by interfering with the main cellular processes regulating cell proliferation and apoptosis are in agreement with previous studies on the effects of HF on other fibrotic diseases. HF can be considered as a candidate for reducing the size of leiomyomas, particularly prior to surgery. This project was funded by NIH PO1HD057877 and R01 HD064402. Authors report no competing interests. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights

  6. Localization of indium-111 in human malignant tumor xenografts and control by chelators

    International Nuclear Information System (INIS)

    Watanabe, Naoyuki; Oriuchi, Noboru; Endo, Keigo; Inoue, Tomio; Tanada, Shuji; Murata, Hajime; Kim, E. Edmund; Sasaki, Yasuhito

    1999-01-01

    The kinetics of soluble indium-111 ( 111 In) in human malignant tumor xenografts and cells was investigated in combination with chelators. Firstly, without chelator, the kinetics of 111 In-chloride was investigated in vitro and in vivo using four human malignant neuroblastoma SK-N-MC, pulmonary papillary adenocarcinoma NCI-H441, pulmonary squamous cell carcinoma PC 9, and colon adenocarcinoma LS 180 cells and xenografts. 111 In was incorporated into tumor cells in vitro to a maximum level during a 60-min incubation. A maximum level of radioactivity was demonstrated in vivo in four human malignant tumors xenografted into nude mice at 24 h postinjection of 111 In-chloride. Secondly, the effect of edetate calcium disodium (CaNa 2 EDTA) on radioactivity in 111 In-labeled tumors xenografts and cells was studied in vitro and in vivo. CaNa 2 EDTA significantly reduced 111 In-activity from the labeled tumor xenografts, whereas it had no affect on the radioactivity in the labeled cells. Thirdly, the effect of CaNa 2 EDTA on radioactivity in human malignant tumors xenografted into nude mice injected with 111 In-chloride was investigated. In one group of mice CaNa 2 EDTA administered intraperitoneally at 1, 22, 34, 46, 58, and 70 h after injection of 111 In-chloride (postadministration), the localization of 111 In at the tumors was significantly decreased at 72 h compared with the control in all four tumor types. In the other group of mice, CaNa 2 EDTA administered intraperitoneally at 12 and 1 h before injection of 111 In-chloride and 1, 22, 34, 46, 58, and 70 h postinjection (pre- and postadministration), the radioactivity of tumors was also significantly decreased at 72 h, and the reduction was greater than that with use of postadministration. In a comparative study, CaNa 3 DTPA had a more powerful effect than CaNa 2 EDTA. In conclusion, 111 In-activity in tumors consists of intracellular and extracellular components, and the extracellular 111 In may be cleared by

  7. An integrated analysis of miRNA and gene copy numbers in xenografts of Ewing's sarcoma

    Directory of Open Access Journals (Sweden)

    Mosakhani Neda

    2012-03-01

    Full Text Available Abstract Background Xenografts have been shown to provide a suitable source of tumor tissue for molecular analysis in the absence of primary tumor material. We utilized ES xenograft series for integrated microarray analyses to identify novel biomarkers. Method Microarray technology (array comparative genomic hybridization (aCGH and micro RNA arrays was used to screen and identify copy number changes and differentially expressed miRNAs of 34 and 14 passages, respectively. Incubated cells used for xenografting (Passage 0 were considered to represent the primary tumor. Four important differentially expressed miRNAs (miR-31, miR-31*, miR-145, miR-106 were selected for further validation by real time polymerase chain reaction (RT-PCR. Integrated analysis of aCGH and miRNA data was performed on 14 xenograft passages by bioinformatic methods. Results The most frequent losses and gains of DNA copy number were detected at 9p21.3, 16q and at 8, 15, 17q21.32-qter, 1q21.1-qter, respectively. The presence of these alterations was consistent in all tumor passages. aCGH profiles of xenograft passages of each series resembled their corresponding primary tumors (passage 0. MiR-21, miR-31, miR-31*, miR-106b, miR-145, miR-150*, miR-371-5p, miR-557 and miR-598 showed recurrently altered expression. These miRNAS were predicted to regulate many ES-associated genes, such as genes of the IGF1 pathway, EWSR1, FLI1 and their fusion gene (EWS-FLI1. Twenty differentially expressed miRNAs were pinpointed in regions carrying altered copy numbers. Conclusion In the present study, ES xenografts were successfully applied for integrated microarray analyses. Our findings showed expression changes of miRNAs that were predicted to regulate many ES associated genes, such as IGF1 pathway genes, FLI1, EWSR1, and the EWS-FLI1 fusion genes.

  8. Celastrol ameliorates ulcerative colitis-related colorectal cancer in mice via suppressing inflammatory responses and epithelial-mesenchymal transition

    Directory of Open Access Journals (Sweden)

    Lianjie eLin

    2016-01-01

    Full Text Available Celastrol, also named as tripterine, is a pharmacologically active ingredient extracted from the root of traditional Chinese herb Tripterygium wilfordii Hook F with potent anti-inflammatory and anti-tumor activities. In the present study, we investigated the effects of celastrol on ulcerative colitis-related colorectal cancer (UC-CRC as well as colorectal cancer (CRC in vivo and in vitro and explored its underlying mechanisms. UC-CRC model was induced in C57BL/6 mice by administration of azoxymethane (AOM and dextran sodium sulfate (DSS. Colonic tumor xenograft models were developed in BALB/c-nu mice by subcutaneous injection with HCT116 and HT-29 cells. Intragastric administration of celastrol (2 mg/kg/d for 14 weeks significantly increased the survival ratio and reduced the multiplicity of colonic neoplasms compared with AOM/DSS model mice. Mechanically, celastrol treatment significantly prevented AOM/DSS-induced up-regulation of expression levels of oncologic markers including mutated p53 and phospho-p53, β-catenin and proliferating cell nuclear antigen (PCNA. In addition, treatment with celastrol inhibited inflammatory responses, as indicated by the decrease of serum tumor necrosis factor-α (TNF-α, interleukin (IL-1β and IL-6, down-regulation of cyclooxygenase-2 (COX-2 and inducible nitric oxide synthase (iNOS, and inactivation of nuclear factor κB (NF-κB. Moreover, celastrol obviously suppressed epithelial mesenchymal transition (EMT through up-regulating E-cadherin and down-regulating N-cadherin, Vimentin and Snail. Additionally, we also demonstrated that celastrol inhibited human CRC cell proliferation and attenuated colonic xenograft tumor growth via reversing EMT. Taken together, celastrol could effectively ameliorate UC-CRC by suppressing inflammatory responses and EMT, suggesting a potential drug candidate for UC-CRC therapy.

  9. N-myc downstream-regulated gene 1 promotes oxaliplatin-triggered apoptosis in colorectal cancer cells via enhancing the ubiquitination of Bcl-2.

    Science.gov (United States)

    Yang, Xiao; Zhu, Fan; Yu, Chaoran; Lu, Jiaoyang; Zhang, Luyang; Lv, Yanfeng; Sun, Jing; Zheng, Minhua

    2017-07-18

    N-myc downstream-regulated gene1 (NDRG1) has been identified as a potent tumor suppressor gene. The molecular mechanisms of anti-tumor activity of NDRG1 involve its suppressive effects on a variety of tumorigenic signaling pathways. The purpose of this study was to investigate the role of NDRG1 in the apoptosis of colorectal cancer (CRC) cells. We first collected the clinical data of locally advanced rectal cancer (LARC) patients receiving oxaliplatin-based neoadjuvant chemotherapy in our medical center. Correlation analysis revealed that NDRG1 positively associated with the downstaging rates and prognosis of patients. Then, the effects of over-expression and depletion of NDRG1 gene on apoptosis of colorectal cancer were tested in vitro and in vivo. NDRG1 over-expression promoted apoptosis in colorectal cancer cells whereas depletion of NDRG1 resulted in resistance to oxaliplatin treatment. Furthermore, we observed that Bcl-2, a major anti-apoptotic protein, was regulated by NDRG1 at post-transcriptional level. By binding Protein kinase Cα (PKCα), a classical regulating factor of Bcl-2, NDRG1 enhanced the ubiquitination and degradation of Bcl-2, thus promoting apoptosis in CRC cells. In addition, NDRG1 inhibited tumor growth and promoted apoptosis in mouse xenograft model. In conclusion,NDRG1 promotes oxaliplatin-triggered apoptosis in colorectal cancer. Therefore, colorectal cancer patients can be stratified by the expression level of NDRG1. NDRG1-positive patients may benefit from oxaliplatin-containing chemotherapy regimens whereas those with negative NDRG1 expression should avoid the usage of this cytotoxic drug.

  10. Challenging the Cancer Molecular Stratification Dogma: Intratumoral Heterogeneity Undermines Consensus Molecular Subtypes and Potential Diagnostic Value in Colorectal Cancer.

    Science.gov (United States)

    Dunne, Philip D; McArt, Darragh G; Bradley, Conor A; O'Reilly, Paul G; Barrett, Helen L; Cummins, Robert; O'Grady, Tony; Arthur, Ken; Loughrey, Maurice B; Allen, Wendy L; McDade, Simon S; Waugh, David J; Hamilton, Peter W; Longley, Daniel B; Kay, Elaine W; Johnston, Patrick G; Lawler, Mark; Salto-Tellez, Manuel; Van Schaeybroeck, Sandra

    2016-08-15

    A number of independent gene expression profiling studies have identified transcriptional subtypes in colorectal cancer with potential diagnostic utility, culminating in publication of a colorectal cancer Consensus Molecular Subtype classification. The worst prognostic subtype has been defined by genes associated with stem-like biology. Recently, it has been shown that the majority of genes associated with this poor prognostic group are stromal derived. We investigated the potential for tumor misclassification into multiple diagnostic subgroups based on tumoral region sampled. We performed multiregion tissue RNA extraction/transcriptomic analysis using colorectal-specific arrays on invasive front, central tumor, and lymph node regions selected from tissue samples from 25 colorectal cancer patients. We identified a consensus 30-gene list, which represents the intratumoral heterogeneity within a cohort of primary colorectal cancer tumors. Using a series of online datasets, we showed that this gene list displays prognostic potential HR = 2.914 (confidence interval 0.9286-9.162) in stage II/III colorectal cancer patients, but in addition, we demonstrated that these genes are stromal derived, challenging the assumption that poor prognosis tumors with stem-like biology have undergone a widespread epithelial-mesenchymal transition. Most importantly, we showed that patients can be simultaneously classified into multiple diagnostically relevant subgroups based purely on the tumoral region analyzed. Gene expression profiles derived from the nonmalignant stromal region can influence assignment of colorectal cancer transcriptional subtypes, questioning the current molecular classification dogma and highlighting the need to consider pathology sampling region and degree of stromal infiltration when employing transcription-based classifiers to underpin clinical decision making in colorectal cancer. Clin Cancer Res; 22(16); 4095-104. ©2016 AACRSee related commentary by Morris and

  11. Internal hernia following laparoscopic colorectal surgery

    DEFF Research Database (Denmark)

    Svraka, Melina; Wilhelmsen, Michał; Bulut, Orhan

    2017-01-01

    Although internal hernias are rare complications of laparoscopic colorectal surgery, they can lead to serious outcomes and are associated with a high mortality of up 20 %. AIM OF THE STUDY: The aim of this study was to describe our experience regarding internal herniation following laparoscopic...... colorectal surgery. MATERIALS AND METHODS: From 2009 to 2015, more than 1,093 laparoscopic colorectal procedures were performed, and 6 patients developed internal herniation. Data were obtained from patients' charts and reviewed retrospectively. Perioperative course and outcomes were analyzed. RESULTS: All...... patients were previously operated due to colorectal cancer. Two patients presented with ischemia at laparotomy, and 2 had endoscopic examinations before surgery. One patient was diagnosed with cancer on screening colonoscopy. One patient died after laparotomy. CONCLUSION: Internal herniation that develops...

  12. Colorectal cancer, diabetes and survival : Epidemiological insights

    NARCIS (Netherlands)

    Zanders, M. M. J.; Vissers, P. A. J.; Haak, H. R.; van de Poll-Franse, L.

    Colorectal cancer (CRC) patients with pre-existing diabetes have significantly lower rates of overall survival compared with patients without diabetes. Against this backdrop, the American Diabetes Association and American Cancer Society in 2010 reviewed the scientific literature concerning diabetes

  13. Growth and progression of colorectal cancer

    International Nuclear Information System (INIS)

    Yamada, T.; Ushio, K.; Hirota, T.

    1988-01-01

    There is an increasing interest in the natural history of colorectal carcinoma, now that small polypoid lesions of the large intestine can be detected effectively by radiology and endoscopy. The problems of this histo- and morphogenesis of colorectal cancer have, however, remained unsettled because the observation of the sequential change of a lesion with time by follow-up radiology and/or endoscopy is impossible once its malignancy is proved. Clinically the retrospective review of radiographic findings in overlooked cases is the only means to evaluate the natural history of colorectal cancer. This paper attempts to estimate the growth rate of colorectal cancer, based on a retrospective review of radiographic findings of overlooked cases, and analyses of the radiographic features of small polypoid lesions which may develop into advanced cancers

  14. Meat and colo-rectal cancer.

    Science.gov (United States)

    Hill, M J

    1999-05-01

    In early epidemiological studies of diet and cancer the stress was on the search for causal factors. Population (ecological) studies tended to show a strong correlation between meat intake, particularly red meat, and the risk of colo-rectal cancer. They also tended to show meat to be strongly inversely correlated with cancers of the stomach and oesophagus and liver. Early case-control studies tended to support the postulated role for red meat in colo-rectal carcinogenesis, although more recent case-control studies, particularly those from Europe, have tended to show no relationship. The cohort studies in general failed to detect any relationship between meat intake and colo-rectal cancer risk. The available evidence points to the intake of protective factors such as vegetables and whole-grain cereals being the main determinants of colo-rectal cancer risk, with meat intake only coincidentally related.

  15. Colorectal cancer presenting as bone metastasis

    Directory of Open Access Journals (Sweden)

    M C Suresh Babu

    2017-01-01

    Conclusions: In this study, the patients of colorectal cancer presenting with bone metastasis were of male sex and younger age. The factors that were associated with reduced survival were extraosseous and liver involvement.

  16. Screening of colorectal early cancer by radiology

    International Nuclear Information System (INIS)

    Matsukawa, M.; Usui, Y.; Kobayashi, S.

    1988-01-01

    The incidence of colorectal cancer has been gradually increasing in Japan, and if the present rate of increase is maintained it has been estimated that it will become the most common of all malignant neoplasms by the year 2000. It has been proved that colorectal cancer can be completely cured, if it is treated in its early phase. Early cancer of the large bowel is defined as a cancer which is limited to the mucosal membrane or submucosal layer, regardless of lymph node and distant metastases. Detection of early cancer improves the overall curability of colorectal cancer. The greatest number of early cancers of the large bowel are polypoid lesions in their macroscopic form, and depressed lesions are rarely encountered. Accordingly, the first step in the detection of early cancer starts with the screening of polypoid lesion by radiology and endoscopy. This paper is concerned with diagnostic accuracy of radiology in the screening of colorectal cancer with endoscopic correlation

  17. Cancer immunology and colorectal cancer recurrence

    Czech Academy of Sciences Publication Activity Database

    Vannucci, Luca

    -, č. 3 (2011), s. 1421-1431 ISSN 1945-0524 R&D Projects: GA AV ČR IAA500200917 Institutional research plan: CEZ:AV0Z50200510 Keywords : colorectal cancer * inflammation * tumor Subject RIV: EC - Immunology

  18. Using Positron Emission Tomography with [18F]FDG to Predict Tumor Behavior in Experimental Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Bryan M. Burt

    2001-01-01

    Full Text Available This study investigates the relationship between FDG uptake as determined by positron emission tomography (PET imaging and rates of tumor growth, cellular GLUT1 transporter density, and the activities of hexokinase and glucose-6-phosphatase in a solid tumor implant model. Five different human colorectal xenografts of different growth properties were implanted in athymic rats and evaluated by dynamic 18F-FDG-PET. The phosphorylating and dephosphorylating activities of the key glycolytic enzymes, hexokinase and glucose-6-phosphatase, were measured in these tumor types by spectrophotometric assays and the expression of GLUT1 glucose transporter protein was determined by immunohistochemistry. Correlations among FDG accumulation, hexokinase activity, and tumor doubling time are reported in these colon xenografts. The results indicate that the activity of tumor hexokinase may be a marker of tumor growth rate that can be determined by 18F-FDG-PET imaging. PET scanning may not only be a useful tool for staging patients for extent of disease, but may provide important prognostic information concerning the proliferative rates of malignancies.

  19. The importance of -460 C/T and +405 G/C single nucleotide polymorphisms to the function of vascular endothelial growth factor A in colorectal cancer

    DEFF Research Database (Denmark)

    Hansen, Torben F; Spindler, Karen-Lise G; Lorentzen, Karen A

    2010-01-01

    collected from 113 patients surgically resected for colorectal cancer. SNPs were analysed from genomic DNA by PCR, the VEGF-A gene expression analysis was performed by RT-PCR and protein analysis by ELISA. RESULTS: The T-allele in the -460 C/T SNP and the C-allele in the +405 G/C SNP were associated...... with significantly lower VEGF-A protein levels in normal colorectal tissue. There were no differences in protein levels in the malignant tissue according to genotypes. No differences were observed at the gene expression levels either. CONCLUSION: The results indicate that the two SNPs have a functional influence......PURPOSE: The present study investigated the functional influence of the single nucleotide polymorphisms (SNPs) -460 C/T and +405 G/C at vascular endothelial growth factor A (VEGF-A), mRNA and protein levels in colorectal cancer (CRC) and normal colorectal tissue. METHODS: Blood and tissue were...

  20. Volumetrical and morphological responses of human laryngeal squamous cell carcinoma xenografts treated with fractionated irradiation

    International Nuclear Information System (INIS)

    Hoogenhout, J.; Gasteren, H. van; Jerusalem, C.R.; Kal, H.B.

    1988-01-01

    Xenografts of both primary human laryngeal squamous cell carcinoma and its metastases were irradiated with five daily fractions of 5.0 Gy. Tumor volume changes, morphology, mitotic index and mitotic figures were studied. Primary xenografts disappeared within 17±3 days. Grafts of metastases showed complete regression within 26±5 days, or regrowth after a delay period. Mitotic activity was higher in the grafts of metastases. The number of mitotic figures decreased and ceased within 14 days in the primary tumor, while some were still occasionally noted in the grafts of metastases. Telophase stages were practically absent after the first fraction. This study suggests that the response of metastases to radiation therapy is lower than the response of the primary tumor. (orig.) [de

  1. Tumor Repression of VCaP Xenografts by a Pyrrole-Imidazole Polyamide.

    Directory of Open Access Journals (Sweden)

    Amanda E Hargrove

    Full Text Available Pyrrole-imidazole (Py-Im polyamides are high affinity DNA-binding small molecules that can inhibit protein-DNA interactions. In VCaP cells, a human prostate cancer cell line overexpressing both AR and the TMPRSS2-ERG gene fusion, an androgen response element (ARE-targeted Py-Im polyamide significantly downregulates AR driven gene expression. Polyamide exposure to VCaP cells reduced proliferation without causing DNA damage. Py-Im polyamide treatment also reduced tumor growth in a VCaP mouse xenograft model. In addition to the effects on AR regulated transcription, RNA-seq analysis revealed inhibition of topoisomerase-DNA binding as a potential mechanism that contributes to the antitumor effects of polyamides in cell culture and in xenografts. These studies support the therapeutic potential of Py-Im polyamides to target multiple aspects of transcriptional regulation in prostate cancers without genotoxic stress.

  2. Therapeutic activity of two xanthones in a xenograft murine model of human chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Berthou Christian

    2010-12-01

    Full Text Available Abstract Background We previously reported that allanxanthone C and macluraxanthone, two xanthones purified from Guttiferae trees, display in vitro antiproliferative and proapoptotic activities in leukemic cells from chronic lymphocytic leukemia (CLL and leukemia B cell lines. Results Here, we investigated the in vivo therapeutic effects of the two xanthones in a xenograft murine model of human CLL, developed by engrafting CD5-transfected chronic leukemia B cells into SCID mice. Treatment of the animals with five daily injections of either allanxanthone C or macluraxanthone resulted in a significant prolongation of their survival as compared to control animals injected with the solvent alone (p = 0.0006 and p = 0.0141, respectively. The same treatment of mice which were not xenografted induced no mortality. Conclusion These data show for the first time the in vivo antileukemic activities of two plant-derived xanthones, and confirm their potential interest for CLL therapy.

  3. Clonal dominance between subpopulations of mixed small cell lung cancer xenografts implanted ectopically in nude mice

    DEFF Research Database (Denmark)

    Aabo, K; Vindeløv, L L; Spang-Thomsen, M

    1995-01-01

    Clonal evolution of neoplastic cells during solid tumour growth leads to the emergence of new tumour cell subpopulations with diverging phenotypic characteristics which may alter the behaviour of a malignant disease. Cellular interaction was studied in mixed xenografts in nude mice and during...... clone 54B was found to dominate the parent 54A clone when grown as mixed subcutaneous xenografts in nude mice, whereas no dominance was exerted during in vitro growth. The in vivo dominance could not be explained by differences in growth kinetics between the two tumour cell lines, and the interaction...... was not dependent on 54B being in excess in mixed tumours. The dominance was dependent on close in vivo contact as no remote effect on the growth of 54A was found when the dominating 54B cells were growing in the opposite flank of tumour-bearing mice. Irradiation inactivated 54B cells were unable to exert...

  4. Expression of cadherin and NCAM in human small cell lung cancer cell lines and xenografts

    DEFF Research Database (Denmark)

    Rygaard, K; Møller, C; Bock, E

    1992-01-01

    characterised, the cadherin family and the Ig superfamily member, neural cell adhesion molecule (NCAM). We investigated expression of these two adhesion molecule families in small cell lung cancer (SCLC) cell lines and xenografts by immunoblotting. Nineteen tumours established from 15 patients with SCLC were......Tumour cell adhesion, detachment and aggregation seem to play an important part in tumour invasion and metastasis, and numerous cell adhesion molecules are expressed by tumour cells. Several families of cell-cell adhesion molecules have been described, of which two groups are particularly well...... embryonic development, which may play a role in connection with tumour invasion and metastasis, was found in 14/18 NCAM expressing SCLC tumours. Individual tumours grown as cell lines and as nude mouse xenografts showed no qualitative differences in cadherin or NCAM expression....

  5. Activity of a new nitrosourea (TCNU) in human lung cancer xenografts.

    Science.gov (United States)

    Fergusson, R. J.; Anderson, L. E.; Macpherson, J. S.; Robins, P.; Smyth, J. F.

    1988-01-01

    The activity of a new nitrosourea (TCNU) based on the endogenous amino acid taurine was assessed in three human lung cancer xenografts growing in immunodeficient mice. Moderate activity (specific growth delays of 0.63 and 1.13 compared with controls) was seen in two non-small cell tumours after a single oral administration of 20 mg-1kg. This dose was curative in a small cell xenograft. By using high performance liquid chromatography it was possible to detect parent drug in the tumours as well as the plasma and tissues after oral administration of TCNU. Drug sensitivity was correlated inversely with the amount of the DNA repair enzyme 0(6)-methylguanine-DNA methyltransferase assayed from extracts of the tumour cells but not with the levels of parent drug within the tumour. This compound appears to have unique pharmacokinetic properties compared with other chloroethylnitrosoureas. PMID:3390369

  6. Genetic prognostic markers in colorectal cancer.

    OpenAIRE

    Houlston, R S; Tomlinson, I P

    1997-01-01

    The contribution of molecular genetics to colorectal cancer has been restricted largely to relatively rare inherited tumours and to the detection of germline mutations predisposing to these cancers. However, much is now also known about somatic events leading to colorectal cancer. A number of studies has been undertaken examining possible relations between genetic features and prognostic indices. While many of these studies are small and inconclusive, it is clear that a number of different pa...

  7. Mitotic and apoptotic activity in colorectal neoplasia.

    Science.gov (United States)

    Kohoutova, Darina; Pejchal, Jaroslav; Bures, Jan

    2018-05-18

    Colorectal cancer (CRC) is third most commonly diagnosed cancer worldwide. The aim of the prospective study was to evaluate mitosis and apoptosis of epithelial cells at each stage of colorectal neoplasia. A total of 61 persons were enrolled into the study: 18 patients with non-advanced colorectal adenoma (non-a-A), 13 patients with advanced colorectal adenoma (a-A), 13 patients with CRC and 17 controls: individuals with normal findings on colonoscopy. Biopsy samples were taken from pathology (patients) and healthy mucosa (patients and healthy controls). Samples were formalin-fixed paraffin-embedded and stained with haematoxylin-eosin. Mitotic and apoptotic activity were evaluated in lower and upper part of the crypts and in the superficial compartment. Apoptotic activity was also assessed using detection of activated caspase-3. In controls, mitotic activity was present in lower part of crypts, accompanied with low apoptotic activity. Mitotic and apoptotic activity decreased (to almost zero) in upper part of crypts. In superficial compartment, increase in apoptotic activity was observed. Transformation of healthy mucosa into non-a-A was associated with significant increase of mitotic activity in lower and upper part of the crypts and with significant increase of apoptotic activity in all three compartments; p colorectal neoplasia were observed. Detection of activated caspase-3 confirmed the above findings in apoptotic activity. Significant dysregulation of mitosis and apoptosis during the progression of colorectal neoplasia, corresponding with histology, was confirmed. In patients with sporadic colorectal neoplasia, healthy mucosa does not display different mitotic and apoptotic activity compared to mucosa in healthy controls and therefore adequate endoscopic/surgical removal of colorectal neoplasia is sufficient.

  8. 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....

  9. 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....

  10. [Colorectal cancer (CCR): genetic and molecular alterations].

    Science.gov (United States)

    Juárez-Vázquez, Clara Ibet; Rosales-Reynoso, Mónica Alejandra

    2014-01-01

    The aim of this review is to present a genetic and molecular overview of colorectal carcinogenesis (sporadic and hereditary origin) as a multistage process, where there are a number of molecular mechanisms associated with the development of colorectal cancer and genomic instability that allows the accumulation of mutations in proto-oncogenes and tumor suppressor genes, chromosomal instability, and methylation and microsatellite instability, and the involvement of altered expression of microRNAs' prognosis factors.

  11. Colorectal Cancer - What You Need to Know

    Centers for Disease Control (CDC) Podcasts

    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.

  12. Implications of preoperative hypoalbuminemia in colorectal surgery.

    OpenAIRE

    Truong, A; Hanna, MH; Moghadamyeghaneh, Z; Stamos, MJ

    2016-01-01

    Serum albumin has traditionally been used as a quantitative measure of a patient’s nutritional status because of its availability and low cost. While malnutrition has a clear definition within both the American and European Societies for Parenteral and Enteral Nutrition clinical guidelines, individual surgeons often determine nutritional status anecdotally. Preoperative albumin level has been shown to be the best predictor of mortality after colorectal cancer surgery. Specifically in colorect...

  13. Calcium antagonist radioprotectors do not reduce radiotherapeutic efficacy in three human tumor xenografts

    International Nuclear Information System (INIS)

    Floersheim, G.L.; Racine, C.

    1995-01-01

    One Ewing's sarcoma and 2 colon carcinomas were grown as xenografts in immunosuppressed mice. The mice were treated with diltiazem, nifedipine, nimodipine and nitrendipine. The effect of whole body γ-radiation on the growth of the subcutaneously implanted tumors was assessed. Growth delay or regression of the tumors in mice treated with the calcium antagonists prior to irradiation was not reduced as compared to only irradiated controls. (orig.) [de

  14. Morphological Features of the Porcine Lacrimal Gland and Its Compatibility for Human Lacrimal Gland Xenografting

    OpenAIRE

    Henker, Robert; Scholz, Michael; Gaffling, Simone; Asano, Nagayoshi; Hampel, Ulrike; Garreis, Fabian; Hornegger, Joachim; Paulsen, Friedrich

    2013-01-01

    In this study, we present first data concerning the anatomical structure, blood supply and location of the lacrimal gland of the pig. Our data indicate that the porcine lacrimal gland may serve as a potential xenograft candidate in humans or as an animal model for engineering of a bioartificial lacrimal gland tissue construct for clinical application. For this purpose, we used different macroscopic preparation techniques and digital reconstruction of the histological gland morphology to gain ...

  15. Anterior cruciate ligament reconstruction with a novel porcine xenograft: the initial Italian experience

    Science.gov (United States)

    ZAFFAGNINI, STEFANO; GRASSI, ALBERTO; MUCCIOLI, GIULIO MARIA MARCHEGGIANI; DI SARSINA, TOMMASO ROBERTI; RAGGI, FEDERICO; BENZI, ANDREA; MARCACCI, MAURILIO

    2015-01-01

    At the current state of the art in anterior cruciate ligament (ACL) reconstruction, multiple techniques have been presented but none has given clearly defined and improved results. One of the main issues concerns the choice of graft. The concept of using xenograft tissue, defined as a graft tissue from one species and destined for implantation in an unlike species, was introduced in order to try to overcome the mechanical and biological concerns associated with synthetic materials and the safety and quality concerns and availability problems of allograft tissue. Xenograft tissue carries the risk of producing an immunological reaction. In order to try to overcome or attenuate the immune response against porcine xenograft tissue, the Z-Process® (Aperion Biologics Inc, San Antonio, Texas, USA) has been developed and used to produce the Z-Lig® family of devices for ACL reconstruction procedures. Z-Lig® is a tendon graft with or without bone blocks, sourced from animal tissue in a manner consistent with what has normally been sourced from human tissue, and processed to overcome anti-Gal-mediated rejection and to attenuate other immunological recognition in humans. All this while ensuring sterility, viral inactivation and preservation of mechanical proprieties appropriate for an ACL reconstruction device. The Z-Lig® device has been tested in skeletally mature monkeys and given interesting and promising results from the preclinical performance and safety profile point of view. On this basis, it was possible to proceed with the first clinical trial involving humans, which gave similar encouraging results. The Z-Lig® device has also been implanted in Italy at the Rizzoli Orthopaedic Institute in Bologna, as a part of international multicenter prospective randomized blinded controlled study aimed at comparing xenograft with allograft tissue. PMID:26605257

  16. Establishing Prostate Cancer Patient Derived Xenografts: Lessons Learned From Older Studies

    OpenAIRE

    Russell, Pamela J; Russell, Peter; Rudduck, Christina; Tse, Brian W-C; Williams, Elizabeth D; Raghavan, Derek

    2015-01-01

    Background Understanding the progression of prostate cancer to androgen-independence/castrate resistance and development of preclinical testing models are important for developing new prostate cancer therapies. This report describes studies performed 30 years ago, which demonstrate utility and shortfalls of xenografting to preclinical modeling. Methods We subcutaneously implanted male nude mice with small prostate cancer fragments from transurethral resection of the prostate (TURP) from 29 pa...

  17. Biological characterization of two xenografts derived from human CUPs (carcinomas of unknown primary

    Directory of Open Access Journals (Sweden)

    Bernheim Alain

    2007-12-01

    Full Text Available Abstract Background Carcinomas of unknown primary site (CUP are epithelial malignancies revealed by metastatic lesions in the absence of any detectable primary tumor. Although they often adopt an aggressive clinical pattern, their basic biology remains poorly understood. Laboratory research on their biology have been hampered so far by the absence of cell lines representative of CUPs. Methods We attempted xenografts of CUP clinical specimens in immunodeficient mice and subsequent in vitro culture of transplanted malignant cells. Whenever possible, malignant xenografted or cultured cells were characterized by microsatellite genotyping, immunohistology, electron microscopy, multifish chromosome analysis and search of TP 53 gene mutations. Results Successful xenografts were achieved in 2 cases out of 4. One of them (Capi1 was lost after 3 passages whereas the other one (Capi3 has been adapted to in vitro culture and is currently available to the scientific community with reliable identification based on microsatellite genotyping. Both Capi1 and Capi3 have histological characteristics of adenocarcinomas and display intense expression of EMA, CEA and cytokeratin 7. Multifish chromosome analysis demonstrated a translocation involving chromosomes 4 and 21 in both specimens. Distinct rare missense mutations of the TP53 gene were detected in Capi1 (codon 312 and Capi3 (codon 181; the codon 181 mutation is consistent with a previously reported similar finding in a small series of CUP specimens. Finally, intense membrane expression of c-kit was recorded in Capi3. Conclusion Our data suggest that xenografted tumors can be obtained from a substantial fraction of CUP clinical specimens. The hypothesis of a preferential association of CUPs with TP 53 mutations of codon 181 deserves further investigations. The Capi3 cell line will be a useful tool for assessment of novel c-kit inhibitors.

  18. A comprehensive patient-derived xenograft collection representing the heterogeneity of melanoma

    OpenAIRE

    Krepler, Clemens; Sproesser, Katrin; Brafford, Patricia; Beqiri, Marilda; Garman, Bradley; Xiao, Min; Shannan, Batool; Watters, Andrea; Perego, Michela; Zhang, Gao; Vultur, Adina; Yin, Xiangfan; Liu, Qin; Anastopoulos, Ioannis N; Wubbenhorst, Bradley

    2017-01-01

    Summary: Therapy of advanced melanoma is changing dramatically. Following mutational and biological subclassification of this heterogeneous cancer, several targeted and immune therapies were approved and increased survival significantly. To facilitate further advancements through pre-clinical in vivo modeling, we have established 459 patient-derived xenografts (PDX) and live tissue samples from 384 patients representing the full spectrum of clinical, therapeutic, mutational, and biological he...

  19. Profile of colorectal cancer in Eastern India.

    Science.gov (United States)

    Sarkar, Snigdha; Mukherjee, Ramanuj; Paira, Susil Kumar; Roy, Bipradas; Banerjee, Shubhabrata; Mukherjee, Saibal Kumar

    2012-12-01

    Although colorectal cancer is a major cause of concern in the western population, recent studies are showing the incidence and mortality of colorectal cancer to be rapidly rising in Asia. The present study is an insight into the epidemiological profile of colorectal cancer of a representative Eastern Indian population. Over a period of three years, all histologically proved patients with colorectal cancer were assessed for age, sex, body mass index, dietary habits, socioeconomic status and stage of disease. Of a total of 168 patients male to female ratio was 1.7:1.The mean age of presentation was 47.01 years. Although colorectal cancer has been known as a disease of sedentary obese men, 41.66% of the patients were from a low socioeconomic rural set-up and 40.47% were involved in heavy physical labour with only 15% of being obese; 62% patients were harbouring a locally advanced disease at the time of presentation. The epidemiological pattern of colorectal cancer in India is different from that of the west as regards to earlier age of presentation, prevalence in low socio economic class with low fat diet and scanty meat intake.

  20. Industrial risk factors for colorectal cancer

    International Nuclear Information System (INIS)

    Lashner, B.A.; Epstein, S.S.

    1990-01-01

    Colorectal cancer is the second most common malignancy in the United States, and its incidence rates have sharply increased recently, especially in males. Industrial exposures, both occupational and environmental, are important colorectal cancer risk factors that are generally unrecognized by clinicians. Migration studies have documented that colorectal cancer is strongly associated with environmental risk factors. The causal role of occupational exposures is evidenced by a substantial literature associating specific work practices with increased colorectal cancer risks. Industrially related environmental exposures, including polluted drinking water and ionizing radiation, have also been associated with excess risks. Currently, there is a tendency to attribute colorectal cancer, largely or exclusively, to dietary and other lifestyle factors, thus neglecting these industrially related effects. Concerted efforts are needed to recognize the causal role of industrial risk factors and to encourage government and industry to reduce carcinogenic exposures. Furthermore, cost-effective screening programs for high-risk population groups are critically needed to further reduce deaths from colorectal cancer. 143 references

  1. Atrial fibrillation and survival in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Justin Timothy A

    2004-11-01

    Full Text Available Abstract Background Survival in colorectal cancer may correlate with the degree of systemic inflammatory response to the tumour. Atrial fibrillation may be regarded as an inflammatory complication. We aimed to determine if atrial fibrillation is a prognostic factor in colorectal cancer. Patients and methods A prospective colorectal cancer patient database was cross-referenced with the hospital clinical-coding database to identify patients who had underwent colorectal cancer surgery and were in atrial fibrillation pre- or postoperatively. Results A total of 175 patients underwent surgery for colorectal cancer over a two-year period. Of these, 13 patients had atrial fibrillation pre- or postoperatively. Atrial fibrillation correlated with worse two-year survival (p = 0.04; log-rank test. However, in a Cox regression analysis, atrial fibrillation was not significantly associated with survival. Conclusion The presence or development of atrial fibrillation in patients undergoing surgery for colorectal cancer is associated with worse overall survival, however it was not found to be an independent factor in multivariate analysis.

  2. Operculum bone carp (cyprinus carprio sp.) scaffold is a new potential xenograft material: a preliminary study

    Science.gov (United States)

    Kartiwa, A.; Abbas, B.; Pandansari, P.; Prahasta, A.; Nandini, M.; Fadhlillah, M.; Subroto, T.; Panigoro, R.

    2017-02-01

    Orbital floor fracture with extensive bone loss, would cause herniation of the orbital tissue into the maxillary sinus. Graft implantation should be done on the orbital fracture with extensive bone loss. Different types of grafts have their own characteristics and advantages. Xenograft has been widely studied for use in bone defects. This study was to investigate cyprinus carprio sp. opercula bone as a potential xenograft. The aim of this study was to investigate based on EDS chemical analysis using a ZAF Standardless Method of Quantitative Analysis (Oxide) and SEM examination conducted in the laboratory of Mathematics, Institute of Technology Bandung. Particularly the mass ratio of Ca and P (5.8/3:47), the result is 1.67. This is equivalent to the stoichiometric Hydroxyapatite (HA) (Aoki H, 1991, Science and medical applications of hydroxyapatite, Tokyo: Institute for Medical and Engineering, Tokyo Medical and Dental University). C N O that there is an element of protein/amino acid collagen compound, serves as a matrix together with HA. As shown in the SEM analysis that the matrix is a porous sheet-shaped (oval) that interconnect with each other, which is good scaffold. The pore is composed of large pores >200 microns and smaller pores between the large pores with a size smaller or equal to 10 microns that can serve for the attachment of osteoblast cell. In conclusion, Opercula bone carp (cyprinus carprio sp.) scaffold could be a new potential xenograft material.

  3. A Comprehensive Patient-Derived Xenograft Collection Representing the Heterogeneity of Melanoma

    Directory of Open Access Journals (Sweden)

    Clemens Krepler

    2017-11-01

    Full Text Available Summary: Therapy of advanced melanoma is changing dramatically. Following mutational and biological subclassification of this heterogeneous cancer, several targeted and immune therapies were approved and increased survival significantly. To facilitate further advancements through pre-clinical in vivo modeling, we have established 459 patient-derived xenografts (PDX and live tissue samples from 384 patients representing the full spectrum of clinical, therapeutic, mutational, and biological heterogeneity of melanoma. PDX have been characterized using targeted sequencing and protein arrays and are clinically annotated. This exhaustive live tissue resource includes PDX from 57 samples resistant to targeted therapy, 61 samples from responders and non-responders to immune checkpoint blockade, and 31 samples from brain metastasis. Uveal, mucosal, and acral subtypes are represented as well. We show examples of pre-clinical trials that highlight how the PDX collection can be used to develop and optimize precision therapies, biomarkers of response, and the targeting of rare genetic subgroups. : Krepler et al. have established a collection of melanoma patient-derived xenografts (PDX. Melanoma is a very heterogeneous cancer, and this large collection includes even rare subtypes and genetic aberrations in sufficient numbers. Multiple PDX from therapy-resistant patients are characterized and tested in pre-clinical trials for second line therapies. Keywords: melanoma, patient-derived xenografts, targeted therapy, immune checkpoint blockade, melanoma brain metastasis, in vivo models, BRAF inhibitor resistance, ERK inhibitor, MDM2 inhibitor, PI3K beta inhibitor

  4. Identification of Biomarkers of Necrosis in Xenografts Using Imaging Mass Spectrometry.

    Science.gov (United States)

    Fernández, Roberto; Garate, Jone; Lage, Sergio; Terés, Silvia; Higuera, Mónica; Bestard-Escalas, Joan; López, Daniel H; Guardiola-Serrano, Francisca; Escribá, Pablo V; Barceló-Coblijn, Gwendolyn; Fernández, José A

    2016-02-01

    Xenografts are commonly used to test the effect of new drugs on human cancer. However, because of their heterogeneity, analysis of the results is often controversial. Part of the problem originates in the existence of tumor cells at different metabolic stages: from metastatic to necrotic cells, as it happens in real tumors. Imaging mass spectrometry is an excellent solution for the analysis of the results as it yields detailed information not only on the composition of the tissue but also on the distribution of the biomolecules within the tissue. Here, we use imaging mass spectrometry to determine the distribution of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and their plasmanyl- and plasmenylether derivatives (PC-P/O and PE-P/O) in xenografts of five different tumor cell lines: A-549, NCI-H1975, BX-PC3, HT29, and U-87 MG. The results demonstrate that the necrotic areas showed a higher abundance of Na(+) adducts and of PC-P/O species, whereas a large abundance of PE-P/O species was found in all the xenografts. Thus, the PC/PC-ether and Na(+)/K(+) ratios may highlight the necrotic areas while an increase on the number of PE-ether species may be pointing to the existence of viable tumor tissues. Furthermore, the existence of important changes in the concentration of Na(+) and K(+) adducts between different tissues has to be taken into account while interpreting the imaging mass spectrometry results. Graphical Abstract ᅟ.

  5. Inhibitory effect of Dendrobium officinale polysaccharide on human gastric cancer cell xenografts in nude mice

    Directory of Open Access Journals (Sweden)

    Liying ZHANG

    2017-10-01

    Full Text Available Abstract This study investigated the inhibitory effect of Dendrobium officinale polysaccharide (DOPA on human gastric cancer cell SGC-7901 xenografts in nude mice. The nude mice with SGC-7901 xenografts were randomly divided into model, 5-fluorouracil (5-Fu, low-dose DOPA, middle-dose DOPA and high-dose DOPA group. The later four groups were intragastrically administrated with 100, 200 and 400 mg·kg–1·day–1 DOPA, 400 mg·kg–1·day–1 5-Fu and normal saline, respectively. After treatment for 20 days, the tumor inhibition rate of in high-dose DOPA group was basically equivalent to 5-Fu group. Compared with 5-Fu, DOPA had no obvious toxic side effect on spleen or thymus indexes, routine blood indexes or liver and kidney functions of nude mice. Compared with model group, the serum tumor necrosis factor-α and interleukin-2 levels in middle- and high-dose DOPA group were significantly increased (P < 0.05, Bax protein expression was significantly increased (P < 0.05, and Bcl-2 protein expression was significantly decreased (P < 0.05. DOPA can inhibit the growth of SGC-7901 cell xenografts in nude mice. The mechanism may be related to its increase of serum TNF-α and IL-2 levels, up-regulation of Bax protein expression and down-regulation of Bcl-2 protein expression.

  6. Effects of curcumin on growth of human cervical cancer xenograft in nude mice and underlying mechanism

    Directory of Open Access Journals (Sweden)

    Aixue LIU

    Full Text Available Abstract The present study investigated the effects of curcumin (Cur on growth of human cervical cancer xenograft in nude mice and underlying mechanism. The nude mice modeled with human cervical cancer HeLa cell xenograft were treated with normal saline (control, 3 mg/kg Cisplatin, 50, 100 and 200 mg/kg Cur, respectively. The animal body weight and growth of tumor were measured. The expressions of Bax, Bcl-2, p53, p21, HIF-1α, VEGF and MIF protein in tumor tissue were determined. Results showed that, after treatment for 20 days, the tumor mass and tumor volume in 100 and 200 mg/kg Cur group were significantly lower than control group (P < 0.05. The expressions of Bax, p53 and p21 protein in tumor tissue in 200 mg/kg Cur group were significantly higher than control group (P < 0.05, and the expressions of Bcl-2, HIF-1α, VEGF and MIF protein in tumor tissue in 200 mg/kg Cur group were significantly lower than control group (P < 0.05. Cur can inhibit the growth of HeLa cell xenograft in nude mice. The possible mechanism may be related to its up-regulation of Bax, p53 and p21 protein expression in tumor tissue, and down-regulation of Bcl-2, HIF-1α, VEGF and MIF protein expression.

  7. Assessment of Hypoxia in the Stroma of Patient-Derived Pancreatic Tumor Xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Lohse, Ines; Lourenco, Corey; Ibrahimov, Emin; Pintilie, Melania [Ontario Cancer Institute and Campbell Family Cancer Research Institute, Princess Margaret Cancer Center, University Health Network, 610 University Ave., Toronto, ON M5G2M9 (Canada); Tsao, Ming-Sound [Ontario Cancer Institute and Campbell Family Cancer Research Institute, Princess Margaret Cancer Center, University Health Network, 610 University Ave., Toronto, ON M5G2M9 (Canada); Department of Pathology, University Health Network, 200 Elizabeth Street, Toronto, ON M5G2C4 (Canada); Department of Laboratory Medicine and Pathobiology, 27 King’s College Circle, University of Toronto, Toronto, ON M5S1A1 (Canada); Hedley, David W., E-mail: david.hedley@uhn.ca [Ontario Cancer Institute and Campbell Family Cancer Research Institute, Princess Margaret Cancer Center, University Health Network, 610 University Ave., Toronto, ON M5G2M9 (Canada); Departments of Medical Biophysics University of Toronto, 610 University Ave., Toronto, ON M5G2M9 (Canada); Departments of Medicine, University of Toronto, 610 University Ave., Toronto, ON M5G2M9 (Canada); Department of Medical Oncology and Hematology, Princess Margaret Cancer Center, 610 University Ave., Toronto, ON M5G2M9 (Canada)

    2014-02-26

    The unusually dense stroma of pancreatic cancers is thought to play an important role in their biological aggression. The presence of hypoxia is also considered an adverse prognostic factor. Although it is usually assumed that this is the result of effects of hypoxia on the epithelial component, it is possible that hypoxia exerts indirect effects via the tumor stroma. We therefore measured hypoxia in the stroma of a series of primary pancreatic cancer xenografts. Nine patient-derived pancreatic xenografts representing a range of oxygenation levels were labeled by immunohistochemistry for EF5 and analyzed using semi-automated pattern recognition software. Hypoxia in the tumor and stroma was correlated with tumor growth and metastatic potential. The extent of hypoxia varied from 1%–39% between the different models. EF5 labeling in the stroma ranged from 0–20% between models, and was correlated with the level of hypoxia in the tumor cell area, but not microvessel density. Tumor hypoxia correlated with spontaneous metastasis formation with the exception of one hypoxic model that showed disproportionately low levels of hypoxia in the stroma and was non-metastatic. Our results demonstrate that hypoxia exists in the stroma of primary pancreatic cancer xenografts and suggest that stromal hypoxia impacts the metastatic potential.

  8. [Biomaterials for bone filling: comparisons between autograft, hydroxyapatite and one highly purified bovine xenograft].

    Science.gov (United States)

    Chappard, D; Zhioua, A; Grizon, F; Basle, M F; Rebel, A

    1993-12-01

    Bone grafts are becoming increasingly common in orthopaedics, neurosurgery and periodontology. Twenty one New Zealand rabbits were used in the present study comparing several materials usable as bone substitutes. A 4.5 mm hole was drilled in the inner femoral condyles. Holes were filled with either an autograft (from the opposite condyle), an hydroxylapatite (Bioapatite), or a highly purified bovine xenograft (T650 Lubboc). Animals were sacrificed at 1, 3 and 6 months post implantation and a quantitative analysis of newly-formed bone volume (BNF/IV) and remaining biomaterials (BMAT/IV) was done. In addition, some holes were left unfilled and served as controls. At 6 months, there was no tendency for spontaneous repair in the control animals. The autografted animals have repaired their trabecular mass and architecture within the first month. Hydroxylapatite appeared unresorbed at six months and only thin and scanty new trabeculae were observed. The xenograft induced woven bone trabeculae formation on the first month. This was associated with resorption of the material by two multinucleated cell populations. At six months, the epiphyseal architecture was restored and the biomaterial has disappeared in most cases. Xenografts appear a promising alternative to autografts and allografts, whose infectious risks and ethical problems should always be borne in mind.

  9. Associations of Statin Use With Colorectal Cancer Recurrence and Mortality in a Danish Cohort.

    Science.gov (United States)

    Lash, Timothy L; Riis, Anders H; Ostenfeld, Eva B; Erichsen, Rune; Vyberg, Mogens; Ahern, Thomas P; Thorlacius-Ussing, Ole

    2017-09-15

    In earlier studies of the influence of hydroxymethylglutaryl-coenzyme A reductase inhibitors (also known as statins) on colorectal cancer prognosis, investigators reported a reduced rate of cancer-specific mortality. Studies of recurrence are few and small. Using data from Danish registries, we followed 21,152 patients diagnosed with stage I-III colorectal cancer from 2001 to 2011. We estimated the association between statin use in the preceding year and cancer recurrence, cancer-specific mortality, and all-cause mortality rates. We identified 5,036 recurrences, 7,084 deaths from any cause, and 4,066 deaths from colorectal cancer. After adjustment for potential confounders, statin use was not associated with recurrence (adjusted hazard ratio (aHR) = 1.01, 95% confidence interval (CI): 0.93, 1.09), but it was associated with death from colorectal cancer (aHR = 0.72, 95% CI: 0.65, 0.79) and death from any cause (aHR = 0.72, 95% CI: 0.67, 0.76). Statin use in the year preceding recurrence was associated with a reduced risk of cancer-specific mortality (aHR = 0.83, 95% CI: 0.74, 0.92) but also a reduced risk of death from any other cause (aHR = 0.78, 95% CI: 0.61, 1.00). Statin use was not associated with a reduced rate of colorectal cancer recurrence, but it was associated with a reduced rate of cancer-specific mortality, which suggests that there is no cancer-directed benefit; therefore, there is no basis to prescribe statins to colorectal cancer patients who do not have cardiovascular indications. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Carcinoembryonic antigen promotes colorectal cancer progression by targeting adherens junction complexes

    Energy Technology Data Exchange (ETDEWEB)

    Bajenova, Olga, E-mail: o.bazhenova@spbu.ru [Theodosius Dobzhansky Center for Genome Bioinformatics, St. Petersburg State University, St. Petersburg 199034 (Russian Federation); Department of Genetics and Biotechnology, St. Petersburg State University, St. Petersburg 199034 (Russian Federation); Department of Surgery and Biomedical Sciences, Creighton University, Omaha, NE 68178 (United States); Chaika, Nina [Department of Surgery and Biomedical Sciences, Creighton University, Omaha, NE 68178 (United States); Tolkunova, Elena; Davydov-Sinitsyn, Alexander [Institute of Cytology, Russian Academy of Sciences, St. Petersburg 194064 (Russian Federation); Gapon, Svetlana [Boston Children' s Hospital, Boston, MA 02115 (United States); Thomas, Peter [Department of Surgery and Biomedical Sciences, Creighton University, Omaha, NE 68178 (United States); O’Brien, Stephen [Theodosius Dobzhansky Center for Genome Bioinformatics, St. Petersburg State University, St. Petersburg 199034 (Russian Federation)

    2014-06-10

    Oncomarkers play important roles in the detection and management of human malignancies. Carcinoembryonic antigen (CEA, CEACAM5) and epithelial cadherin (E-cadherin) are considered as independent tumor markers in monitoring metastatic colorectal cancer. They are both expressed by cancer cells and can be detected in the blood serum. We investigated the effect of CEA production by MIP101 colorectal carcinoma cell lines on E-cadherin adherens junction (AJ) protein complexes. No direct interaction between E-cadherin and CEA was detected; however, the functional relationships between E-cadherin and its AJ partners: α-, β- and p120 catenins were impaired. We discovered a novel interaction between CEA and beta-catenin protein in the CEA producing cells. It is shown in the current study that CEA overexpression alters the splicing of p120 catenin and triggers the release of soluble E-cadherin. The influence of CEA production by colorectal cancer cells on the function of E-cadherin junction complexes may explain the link between the elevated levels of CEA and the increase in soluble E-cadherin during the progression of colorectal cancer. - Highlights: • Elevated level of CEA increases the release of soluble E-cadherin during the progression of colorectal cancer. • CEA over-expression alters the binding preferences between E-cadherin and its partners: α-, β- and p120 catenins in adherens junction complexes. • CEA produced by colorectal cancer cells interacts with beta-catenin protein. • CEA over-expression triggers the increase in nuclear beta-catenin. • CEA over-expression alters the splicing of p120 catenin protein.

  11. Polymorphisms in heterocyclic aromatic amines metabolism-related genes are associated with colorectal adenoma risk.

    Science.gov (United States)

    Eichholzer, Monika; Rohrmann, Sabine; Barbir, Aline; Hermann, Silke; Teucher, Birgit; Kaaks, Rudolf; Linseisen, Jakob

    2012-01-01

    Colorectal adenoma (CRA) and colorectal cancer (CRC) risks have been linked to the intake of red and processed meat. Heterocyclic aromatic amines (HCA) formed herein during high temperature cooking, are metabolized by a variety of enzymes, and allelic variation in the coding genes could influence individual CRA risk. Associations of polymorphisms in NAT1, NAT2, GSTA1, SULT1A1, CYP1A2, UGT1A7, UGT1A9, GSTP1 genes with colorectal adenoma risk were investigated in a nested case-control study of the EPIC-Heidelberg cohort including 428 cases matched by age, sex and year of recruitment with one or two controls (n=828) with negative colonoscopy per case. Genoyping was preformed with the Sequenom MassArray system and the LightCycler 480. Conditional logistic regression was used to compute odds ratios (OR) and corresponding 95% confidence intervals (CI). For rs15561 (NAT1) and rs1057126 (NAT1), the rarer allel was significantly inversely associated with adenoma risk OR=0.80 (95% CI 0.65-0.97) and (OR=0.81 (95% CI 0.65-0.99) and, respectively). For the combined NAT2 alleles encoding for enzymes with medium (versus slow) activity we also observed a significantly inverse association with adenoma risk (OR=0.75; 95% CI 0.85-0.97). In addition, homozygous carriers of the A allele of rs3957357 (GSTA1), i.e., those with a decreased enzyme activity, had a decreased risk of colorectal adenoma with an OR of 0.68 (95% CI 0.50-0.92; AA versus GG/GA). Polymorphisms in the other tested genes did not modify the risk of colorectal adenomas. In conclusion, polymorphisms in NAT1, NAT2, and GSTA1 are related to colorectal adenoma risk in this German cohort.

  12. Carcinoembryonic antigen promotes colorectal cancer progression by targeting adherens junction complexes

    International Nuclear Information System (INIS)

    Bajenova, Olga; Chaika, Nina; Tolkunova, Elena; Davydov-Sinitsyn, Alexander; Gapon, Svetlana; Thomas, Peter; O’Brien, Stephen

    2014-01-01

    Oncomarkers play important roles in the detection and management of human malignancies. Carcinoembryonic antigen (CEA, CEACAM5) and epithelial cadherin (E-cadherin) are considered as independent tumor markers in monitoring metastatic colorectal cancer. They are both expressed by cancer cells and can be detected in the blood serum. We investigated the effect of CEA production by MIP101 colorectal carcinoma cell lines on E-cadherin adherens junction (AJ) protein complexes. No direct interaction between E-cadherin and CEA was detected; however, the functional relationships between E-cadherin and its AJ partners: α-, β- and p120 catenins were impaired. We discovered a novel interaction between CEA and beta-catenin protein in the CEA producing cells. It is shown in the current study that CEA overexpression alters the splicing of p120 catenin and triggers the release of soluble E-cadherin. The influence of CEA production by colorectal cancer cells on the function of E-cadherin junction complexes may explain the link between the elevated levels of CEA and the increase in soluble E-cadherin during the progression of colorectal cancer. - Highlights: • Elevated level of CEA increases the release of soluble E-cadherin during the progression of colorectal cancer. • CEA over-expression alters the binding preferences between E-cadherin and its partners: α-, β- and p120 catenins in adherens junction complexes. • CEA produced by colorectal cancer cells interacts with beta-catenin protein. • CEA over-expression triggers the increase in nuclear beta-catenin. • CEA over-expression alters the splicing of p120 catenin protein

  13. Pneumatosis Coli Mimicking Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Teresa Jacob

    2014-01-01

    Full Text Available Pneumatosis coli (PC is a rare condition of the gastrointestinal tract involving extraluminal gas confined within the bowel wall. We report the case of a 40-year-old gentleman presenting clinically and endoscopically with suspected colorectal cancer. In light of the patient’s red flag symptoms, and carpet of polyps seen endoscopically, surgical management by an anterior resection was performed with the patient making a successful recovery. Histological analysis of the resected specimen confirmed pneumatosis coli with no evidence of colonic neoplasia. Although PC can be an incidental finding in asymptomatic patients and considered a benign condition, it can also present as a life-threatening emergency with bowel necrosis and obstruction requiring emergency surgical intervention. Also, when PC mimics malignancy, surgical management is the most appropriate step to ensure that the diagnosis of cancer is not missed.

  14. Personalizing therapy for colorectal cancer.

    Science.gov (United States)

    Wong, Ashley; Ma, Brigette B Y

    2014-01-01

    Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. Several important scientific discoveries in the molecular biology of CRC have changed clinical practice in oncology. These included the comprehensive genome-wide profiling of CRC by the Cancer Genome Atlas Network, the discovery of mutations along the RAS-RAF signaling pathway as major determinants of response to antibodies against the epidermal growth factor receptor, the elucidation of new molecular subsets of CRC or gene signatures that may predict clinical outcome after adjuvant chemotherapy, and the innovative targeting of the family of vascular endothelial growth factor and receptors. These new data have allowed oncologists to individualize drug therapy on the basis of a patient's tumor's unique molecular profile, especially in the management of metastatic CRC. This review article will discuss the progress of personalized medicine in the contemporary management of CRC. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  15. Environmental Factors and Colorectal Tumor Risk in Individuals With Hereditary Nonpolyposis Colorectal Cancer

    NARCIS (Netherlands)

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

    2007-01-01

    Background & Aims: Individuals with hereditary nonpolyposis colorectal cancer (HNPCC) are at increased risk for colorectal cancer. Environmental factors might play a role in HNPCC-associated carcinogenesis. The aim of this study was to gain insight into the effects of environmental factors on

  16. Regorafenib (BAY 73-4506): antitumor and antimetastatic activities in preclinical models of colorectal cancer.

    Science.gov (United States)

    Schmieder, Roberta; Hoffmann, Jens; Becker, Michael; Bhargava, Ajay; Müller, Tina; Kahmann, Nicole; Ellinghaus, Peter; Adams, Robert; Rosenthal, André; Thierauch, Karl-Heinz; Scholz, Arne; Wilhelm, Scott M; Zopf, Dieter

    2014-09-15

    Regorafenib, a novel multikinase inhibitor, has recently demonstrated overall survival benefits in metastatic colorectal cancer (CRC) patients. Our study aimed to gain further insight into the molecular mechanisms of regorafenib and to assess its potential in combination therapy. Regorafenib was tested alone and in combination with irinotecan in patient-derived (PD) CRC models and a murine CRC liver metastasis model. Mechanism of action was investigated using in vitro functional assays, immunohistochemistry and correlation with CRC-related oncogenes. Regorafenib demonstrated significant inhibition of growth-factor-mediated vascular endothelial growth factor receptor (VEGFR) 2 and VEGFR3 autophosphorylation, and intracellular VEGFR3 signaling in human umbilical vascular endothelial cells (HuVECs) and lymphatic endothelial cells (LECs), and also blocked migration of LECs. Furthermore, regorafenib inhibited proliferation in 19 of 25 human CRC cell lines and markedly slowed tumor growth in five of seven PD xenograft models. Combination of regorafenib with irinotecan significantly delayed tumor growth after extended treatment in four xenograft models. Reduced CD31 staining indicates that the antiangiogenic effects of regorafenib contribute to its antitumor activity. Finally, regorafenib significantly delayed disease progression in a murine CRC liver metastasis model by inhibiting the growth of established liver metastases and preventing the formation of new metastases in other organs. In addition, our results suggest that regorafenib displays antimetastatic activity, which may contribute to its efficacy in patients with metastatic CRC. Combination of regorafenib and irinotecan demonstrated an increased antitumor effect and could provide a future treatment option for CRC patients. © 2013 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.

  17. Potential role of TRIM3 as a novel tumour suppressor in colorectal cancer (CRC) development.

    Science.gov (United States)

    Piao, Mei-Yu; Cao, Hai-Long; He, Na-Na; Xu, Meng-Que; Dong, Wen-Xiao; Wang, Wei-Qiang; Wang, Bang-Mao; Zhou, Bing

    2016-01-01

    Colorectal cancer (CRC) is the third leading cause of cancer-related mortality in the United States. Recent cancer genome-sequencing efforts and complementary functional studies have led to the identification of a collection of candidate 'driver' genes involved in CRC tumorigenesis. Tripartite motif (TRIM3) is recently identified as a tumour suppressor in glioblastoma but this tumour-suppressive function has not been investigated in CRC. In this study, we investigated the potential role of TRIM3 as a tumour suppressor in CRC development by manipulating the expression of TRIM3 in two authentic CRC cell lines, HCT116 and DLD1, followed by various functional assays, including cell proliferation, colony formation, scratch wound healing, soft agar, and invasion assays. Xenograft experiment was performed to examine in vivo tumour-suppressive properties of TRIM3. Small-interfering RNA (siRNA) mediated knockdown of TRIM3 conferred growth advantage in CRC cells. In contrast, overexpression of TRIM3 affected cell survival, cell migration, anchorage independent growth and invasive potential in CRC cells. In addition, TRIM3 was found to be down-regulated in human colon cancer tissues compared with matched normal colon tissues. Overexpression of TRIM3 significantly inhibited tumour growth in vivo using xenograft mouse models. Mechanistic investigation revealed that TRIM3 can regulate p53 protein level through its stabilisation. TRIM3 functions as a tumour suppressor in CRC progression. This tumour-suppressive function is exerted partially through regulation of p53 protein. Therefore, this protein may represent a novel therapeutic target for prevention or intervention of CRC.

  18. Overcoming IGF1R/IR Resistance Through Inhibition of MEK Signaling in Colorectal Cancer Models

    Science.gov (United States)

    Flanigan, Sara A.; Pitts, Todd M.; Newton, Timothy P.; Kulikowski, Gillian N.; Tan, Aik Choon; McManus, Martine C.; Spreafico, Anna; Kachaeva, Maria I.; Selby, Heather M.; Tentler, John J.; Eckhardt, S. Gail; Leong, Stephen

    2013-01-01

    Purpose Results from clinical trials involving resistance to molecularly targeted therapies have revealed the importance of rational single agent and combination treatment strategies. In this study, we tested the efficacy of a type 1 insulin-like growth factor receptor (IGF1R)/insulin receptor (IR) tyrosine kinase inhibitor (TKI), OSI-906, in combination with a MEK 1/2 inhibitor based on evidence that the MAPK pathway was upregulated in colorectal cancer (CRC) cell lines that were resistant to OSI-906. Experimental Design The antiproliferative effects of OSI-906 and the MEK 1/2 inhibitor U0126, were analyzed both as single agents and in combination in 13 CRC cell lines in vitro. Apoptosis, downstream effector proteins, and cell cycle were also assessed. Additionally, the efficacy of OSI-906 combined with the MEK 1/2 inhibitor selumetinib (AZD6244, ARRY-142886), was evaluated in vivo using human CRC xenograft models. Results The combination of OSI-906 and U0126 resulted in synergistic effects in 11 out of 13 CRC cell lines tested. This synergy was variably associated with apoptosis or cell cycle arrest in addition to molecular effects on pro-survival pathways. The synergy was also reflected in the in vivo xenograft studies following treatment with the combination of OSI-906 and selumetinib. Conclusions Results from this study demonstrate synergistic antiproliferative effects in response to the combination of OSI-906 with a MEK 1/2 inhibitor in CRC cell line models both in vitro and in vivo, which supports the rational combination of OSI-906 with a MEK inhibitor in patients with CRC. PMID:24045180

  19. Targeting of human interleukin-12B by small hairpin RNAs in xenografted psoriatic skin

    Directory of Open Access Journals (Sweden)

    Jakobsen Maria

    2011-02-01

    Full Text Available Abstract Background Psoriasis is a chronic inflammatory skin disorder that shows as erythematous and scaly lesions. The pathogenesis of psoriasis is driven by a dysregulation of the immune system which leads to an altered cytokine production. Proinflammatory cytokines that are up-regulated in psoriasis include tumor necrosis factor alpha (TNFα, interleukin-12 (IL-12, and IL-23 for which monoclonal antibodies have already been approved for clinical use. We have previously documented the therapeutic applicability of targeting TNFα mRNA for RNA interference-mediated down-regulation by anti-TNFα small hairpin RNAs (shRNAs delivered by lentiviral vectors to xenografted psoriatic skin. The present report aims at targeting mRNA encoding the shared p40 subunit (IL-12B of IL-12 and IL-23 by cellular transduction with lentiviral vectors encoding anti-IL12B shRNAs. Methods Effective anti-IL12B shRNAs are identified among a panel of shRNAs by potency measurements in cultured cells. The efficiency and persistency of lentiviral gene delivery to xenografted human skin are investigated by bioluminescence analysis of skin treated with lentiviral vectors encoding the luciferase gene. shRNA-expressing lentiviral vectors are intradermally injected in xenografted psoriatic skin and the effects of the treatment evaluated by clinical psoriasis scoring, by measurements of epidermal thickness, and IL-12B mRNA levels. Results Potent and persistent transgene expression following a single intradermal injection of lentiviral vectors in xenografted human skin is reported. Stable IL-12B mRNA knockdown and reduced epidermal thickness are achieved three weeks after treatment of xenografted psoriatic skin with lentivirus-encoded anti-IL12B shRNAs. These findings mimick the results obtained with anti-TNFα shRNAs but, in contrast to anti-TNFα treatment, anti-IL12B shRNAs do not ameliorate the psoriatic phenotype as evaluated by semi-quantitative clinical scoring and by

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

    Science.gov (United States)

    ... in the colon and rectum is often called colorectal cancer. But in this brochure we use the term ... tests can be used to find polyps or colorectal cancer. Each can be used alone. Sometimes they are ...

  1. Colorectal Cancer Prevention (PDQ®)—Patient Version

    Science.gov (United States)

    Colorectal cancer prevention strategies can include avoiding known risk factors, having a healthy lifestyle, taking aspirin, and removing polyps. Learn more about preventing colorectal cancer in this expert-reviewed summary.

  2. Pathological and Biological Aspects of Colorectal Cancer Treatment.

    NARCIS (Netherlands)

    Gosens, M.J.E.M.

    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

  3. Advances in endoscopic ultrasound imaging of colorectal diseases

    DEFF Research Database (Denmark)

    Cârțână, Elena Tatiana; Gheonea, Dan Ionuț; Săftoiu, Adrian

    2016-01-01

    in colorectal cancer, the monitoring of disease activity in inflammatory bowel disease based on quantification of bowel wall vascularization, and differentiating between benign and malignant subepithelial tumours. Recent reports suggest that EUS elastography enables highly accurate discrimination of colorectal...

  4. Laser photocoagulation in the palliation of colorectal malignancies

    NARCIS (Netherlands)

    Mathus-Vliegen, E. M.; Tytgat, G. N.

    1986-01-01

    Besides surgical intervention, there are virtually no palliative treatment modalities available for bleeding and/or obstructing colorectal malignancy. The usefulness and safety of laser photocoagulation was prospectively investigated in 63 patients with colorectal cancer. The merits were evaluated

  5. Multi-modal magnetic resonance imaging and histology of vascular function in xenografts using macromolecular contrast agent hyperbranched polyglycerol (HPG-GdF).

    Science.gov (United States)

    Baker, Jennifer H E; McPhee, Kelly C; Moosvi, Firas; Saatchi, Katayoun; Häfeli, Urs O; Minchinton, Andrew I; Reinsberg, Stefan A

    2016-01-01

    Macromolecular gadolinium (Gd)-based contrast agents are in development as blood pool markers for MRI. HPG-GdF is a 583 kDa hyperbranched polyglycerol doubly tagged with Gd and Alexa 647 nm dye, making it both MR and histologically visible. In this study we examined the location of HPG-GdF in whole-tumor xenograft sections matched to in vivo DCE-MR images of both HPG-GdF and Gadovist. Despite its large size, we have shown that HPG-GdF extravasates from some tumor vessels and accumulates over time, but does not distribute beyond a few cell diameters from vessels. Fractional plasma volume (fPV) and apparent permeability-surface area product (aPS) parameters were derived from the MR concentration-time curves of HPG-GdF. Non-viable necrotic tumor tissue was excluded from the analysis by applying a novel bolus arrival time (BAT) algorithm to all voxels. aPS derived from HPG-GdF was the only MR parameter to identify a difference in vascular function between HCT116 and HT29 colorectal tumors. This study is the first to relate low and high molecular weight contrast agents with matched whole-tumor histological sections. These detailed comparisons identified tumor regions that appear distinct from each other using the HPG-GdF biomarkers related to perfusion and vessel leakiness, while Gadovist-imaged parameter measures in the same regions were unable to detect variation in vascular function. We have established HPG-GdF as a biocompatible multi-modal high molecular weight contrast agent with application for examining vascular function in both MR and histological modalities. Copyright © 2015 John Wiley & Sons, Ltd.

  6. Single and 30 fraction tumor control doses correlate in xenografted tumor models: implications for predictive assays

    International Nuclear Information System (INIS)

    Gerweck, Leo E.; Dubois, Willum; Baumann, Michael; Suit, Herman D.

    1995-01-01

    Purpose/Objective: In a previous publication we reported that laboratory assays of tumor clonogen number, in combination with intrinsic radiosensitivity measured in-vitro, accurately predicted the rank-order of single fraction 50% tumor control doses, in six rodent and xenografted human tumors. In these studies, tumor hypoxia influenced the absolute value of the tumor control doses across tumor types, but not their rank-order. In the present study we hypothesize that determinants of the single fraction tumor control dose, may also strongly influence the fractionaled tumor control doses, and that knowledge of tumor clonogen number and their sensitivity to fractionated irradiation, may be useful for predicting the relative sensitivity of tumors treated by conventional fractionated irradiation. Methods/Materials: Five tumors of human origin were used for these studies. Special care was taken to ensure that all tumor control dose assays were performed over the same time frame, i.e., in-vitro cells of a similar passage were used to initiate tumor sources which were expanded and used in the 3rd or 4th generation. Thirty fraction tumor control doses were performed in air breathing mice, under normal blood flow conditions (two fractions/day). The results of these studies have been previously published. For studies under uniformly (clamp) hypoxic conditions, tumors arising from the same transplantation were randomized into single or fractionated dose protocols. For estimation of the fractionated TCD50 under hypoxic conditions, tumors were exposed to six 5.4 Gy fractions (∼ 2 Gy equivalent under air), followed by graded 'top-up' dose irradiation for determination of the TCD50; the time interval between doses was 6-9 hours. The single dose equivalent of the six 5.4 Gy doses was used to calculate an extrapolated 30 fraction hypoxic TCD50. Results: Fractionation substantially increased the dose required for tumor control in 4 of the 5 tumors investigated. For these 4 tumors

  7. Cetuximab Reduces the Accumulation of Radiolabeled Bevacizumab in Cancer Xenografts without Decreasing VEGF Expression

    NARCIS (Netherlands)

    Heskamp, Sandra; Boerman, Otto C.; Molkenboer-Kuenen, Janneke D. M.; Sweep, Fred C. G. J.; Geurts-Moespot, Anneke; Engelhardt, Mallory S.; van der Graaf, Winette T. A.; Oyen, Wim J. G.; van Laarhoven, Hanneke W. M.

    2014-01-01

    Bevacizumab and cetuximab are approved for the treatment of cancer. However, in advanced colorectal cancer, addition of cetuximab to chemotherapy with bevacizumab did not improve survival. The reason for the lack of activity remains unclear. The aim of this study was to determine the effect of

  8. Cetuximab reduces the accumulation of radiolabeled bevacizumab in cancer xenografts without altering VEGF expression

    NARCIS (Netherlands)

    Heskamp, S.; Boerman, O.C.; Molkenboer-Kuenen, J.D.M.; Sweep, F.C.; Geurts-Moespot, A.; Engelhardt, M.S.; Graaf, W.T.A. van der; Oyen, W.J.G.; Laarhoven, H.W.M. van

    2014-01-01

    Introduction: Bevacizumab and cetuximab are approved for the treatment of cancer. However, in advanced colorectal cancer, addition of cetuximab to chemotherapy with bevacizumab did not improve survival. The reason for the lack of activity remains unclear. The aim of this study was to determine the

  9. Self-renewal molecular mechanisms of colorectal cancer stem cells

    OpenAIRE

    Pan, Tianhui; Xu, Jinghong; Zhu, Yongliang

    2016-01-01

    Colorectal cancer stem cells (CCSCs) represent a small fraction of the colorectal cancer cell population that possess self-renewal and multi-lineage differentiation potential and drive tumorigenicity. Self-renewal is essential for the malignant biological behaviors of colorectal cancer stem cells. While the self-renewal molecular mechanisms of colorectal cancer stem cells are not yet fully understood, the aberrant activation of signaling pathways, such as Wnt, Notch, transforming growth facto...

  10. Long non-coding RNA AFAP1-AS1 facilitates tumor growth and promotes metastasis in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Xu Han

    Full Text Available BACKGROUND AND OBJECTIVE: Long non-coding RNAs can regulate tumorigenesis of various cancers. Dys-regulation of lncRNA-AFAP1-AS1 has not been studied in colorectal carcinoma (CRC. This study was to examine the function involvement of AFAP1-AS1 in tumor growth and metastasis of CRC. METHODS: Relative expression of AFAP1-AS1 in CRC tissues and CRC cells lines was determined using quantitative real-time PCR (qRT-PCR. Functional involvement of AFAP1-AS1 in tumor proliferation and metastasis was evaluated in AFAP1-AS1-specific siRNA-treated CRC cells and in CRC cell xenograft. Expression of epithelial-mesenchymal transition (EMT-related gene expression was determined using western blot. RESULTS: Relative expression of AFAP1-AS1 was significantly elevated in CRC tissues and CRC HCT116 and SW480 cell lines. AFAP1-AS1 knock-down suppressed SW480 cell proliferation, colony formation, migration and invasion. Also AFAP1-AS1 knock-down inhibited tumor metastasis-associated genes expression in terms of EMT. This carcinostatic action by AFAP1-AS1 knock-down was further confirmed by suppression of tumor formation and hepatic metastasis of CRC cells in nude mice. CONCLUSION: lncRNA-AFAP1-AS1 knock-down exhibits antitumor effect on colorectal carcinoma in respects of suppression of cell proliferation and metastasis of cancer cells.

  11. Screening for colorectal cancer in defunctioned colons.

    Science.gov (United States)

    Akbar, Fayyaz; Quyn, Aaron; Steele, Robert

    2018-01-01

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

  12. Establishment of canine hemangiosarcoma xenograft models expressing endothelial growth factors, their receptors, and angiogenesis-associated homeobox genes

    International Nuclear Information System (INIS)

    Kodama, Atsushi; Yanai, Tokuma; Sakai, Hiroki; Matsuura, Satoko; Murakami, Mami; Murai, Atsuko; Mori, Takashi; Maruo, Kouji; Kimura, Tohru; Masegi, Toshiaki

    2009-01-01

    Human hemangiosarcoma (HSA) tends to have a poor prognosis; its tumorigenesis has not been elucidated, as there is a dearth of HSA clinical specimens and no experimental model for HSA. However, the incidence of spontaneous HSA is relatively high in canines; therefore, canine HSA has been useful in the study of human HSA. Recently, the production of angiogenic growth factors and their receptors in human and canine HSA has been reported. Moreover, the growth-factor environment of HSA is very similar to that of pathophysiological angiogenesis, which some homeobox genes regulate in the transcription of angiogenic molecules. In the present study, we established 6 xenograft canine HSA tumors and detected the expression of growth factors, their receptors, and angiogenic homeobox genes. Six primary canine HSAs were xenografted to nude mice subcutaneously and serially transplanted. Subsequently, the expressions of vascular endothelial growth factor (VEGF)-A, basic fibroblast growth factors (bFGF), flt-1 and flk-1 (receptors of VEGF-A), FGFR-1, and angiogenic homeobox genes HoxA9, HoxB3, HoxB7, HoxD3, Pbx1, and Meis1 were investigated in original and xenograft tumors by histopathology, immunostaining, and reverse transcription polymerase chain reaction (RT-PCR), using canine-specific primer sets. Histopathologically, xenograft tumors comprised a proliferation of neoplastic cells that were varied in shape, from spindle-shaped and polygonal to ovoid; some vascular-like structures and vascular clefts of channels were observed, similar to those in the original tumors. The expression of endothelial markers (CD31 and vWF) was detected in xenograft tumors by immunohistochemistry and RT-PCR. Moreover, the expression of VEGF-A, bFGF, flt-1, flk-1, FGFR-1, HoxA9, HoxB3, HoxB7, HoxD3, Pbx1, and Meis1 was detected in xenograft tumors. Interestingly, expressions of bFGF tended to be higher in 3 of the xenograft HSA tumors than in the other tumors. We established 6 xenograft canine HSA

  13. Colorectal Anastomoses : Surgical outcome and prevention of anastomotic leakage

    NARCIS (Netherlands)

    Bakker, Ilsalien

    2016-01-01

    Colorectal surgery is a frequently performed procedure with more than 10.000 annual resections in the Netherlands. The majority of resections are performed for colorectal cancer. The first part of this thesis focused on outcome of colorectal cancer surgery in the Netherlands based on the nationwide

  14. 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 ...

  15. Colorectal liver metastases: factors affecting outcome after surgery

    NARCIS (Netherlands)

    Snoeren, N.

    2013-01-01

    Colorectal cancer is the second leading cause of cancer related death in Europe. The overall survival rate of patients with colorectal cancer is greatly affected by the presence of liver metastases, which occurs in about 50% of patients. Radical resection of colorectal liver metastases means a

  16. Ovarian tumor attachment, invasion and vascularization reflect unique microenvironments in the peritoneum:Insights from xenograft and mathematical models

    Directory of Open Access Journals (Sweden)

    Mara P. Steinkamp

    2013-05-01

    Full Text Available Ovarian cancer relapse is often characterized by metastatic spread throughout the peritoneal cavity with tumors attached to multiple organs. In this study, interaction of ovarian tumor cells with the peritoneal tumor microenvironment was evaluated in a xenograft model based on intraperitoneal injection of fluorescent SKOV3.ip1 ovarian cancer cells. Intra-vital microscopy of mixed GFP-RFP cell populations injected into the peritoneum demonstrated that tumor cells aggregate and attach as mixed spheroids, emphasizing the importance of homotypic adhesion in tumor formation. Electron microscopy provided high resolution structural information about local attachment sites. Experimental measurements from the mouse model were used to build a three-dimensional cellular Potts ovarian tumor model (OvTM that examines ovarian tumor cell attachment, chemotaxis, growth and vascularization. OvTM simulations provide insight into the relative influence of tumor cell-cell adhesion, oxygen availability, and local architecture on tumor growth and morphology. Notably, tumors on the mesentery, omentum or spleen readily invade the open architecture, while tumors attached to the gut encounter barriers that restrict invasion and instead rapidly expand into the peritoneal space. Simulations suggest that rapid neovascularization of SKOV3.ip1 tumors is triggered by constitutive release of angiogenic factors in the absence of hypoxia. This research highlights the importance of cellular adhesion and tumor microenvironment in the seeding of secondary ovarian tumors on diverse organs within the peritoneal cavity. Results of the OvTM simulations indicate that invasion is strongly influenced by features underlying the mesothelial lining at different sites, but is also affected by local production of chemotactic factors. The integrated in vivo mouse model and computer simulations provide a unique platform for evaluating targeted therapies for ovarian cancer relapse.

  17. Toward standardizing and reporting colorectal cancer screening indicators on an international level: The International Colorectal Cancer Screening Network

    NARCIS (Netherlands)

    Benson, Victoria S.; Atkin, Wendy S.; Green, Jane; Nadel, Marion R.; Patnick, Julietta; Smith, Robert A.; Villain, Patricia; Patnick, J.; Atkin, W. S.; Altenhofen, L.; Ancelle-Park, R.; Benson, V. S.; Green, J.; Levin, T. R.; Moss, S. M.; Nadel, M.; Ransohoff, D.; Segnan, N.; Smith, R. A.; Villain, P.; Weller, D.; Koukari, A.; Young, G.; López-Kostner, F.; Antoljak, N.; Suchánek, S.; Zavoral, M.; Holten, I.; Malila, N.; Salines, E.; Brenner, G.; Herszényi, L.; Tulassay, Z.; Rennert, G.; Senore, C.; Zappa, M.; Zorzi, M.; Saito, H.; Leja, M.; Dekker, E.; Jansen, J.; Hol, L.; Kuipers, E.; Kaminski, M. F.; Regula, J.; Sfarti, C.; Trifan, A.; Tang, C.-L.; Hrcka, R.; Binefa, G.; Espinàs, J. A.; Peris, M.; Chen, T. H.; Steele, R.; Pou, G.; Bisges, D.; Dwyer, D.; Groves, C.; Courteau, S.; Kramer, R.; Siegenthaler, K.; Lane, D.; Herrera, C.; Rogers, J.; Rojewski, M.; Wolf, Holly; Sung, J. J.; Ling, K.; Bryant, H.; Rabeneck, L.; Dale, J.; Sware, L.; Yang, H.; Viguier, J.; Von Karsa, L.; Kupcinskas, L.; Deutekom, M.; Törnberg, S.; Austoker, J.; Beral, V.; Monk, C.; Valori, R.; Watson, J.; Kobrin, S.; Pignone, M.; Taplin, S.

    2012-01-01

    The International Colorectal Cancer Screening Network was established in 2003 to promote best practice in the delivery of organized colorectal cancer screening programs. To facilitate evaluation of such programs, we defined a set of universally applicable colorectal cancer screening measures and

  18. Primary prevention of colorectal cancer: myth or reality?

    Science.gov (United States)

    Crosara Teixeira, Marcela; Braghiroli, Maria Ignez; Sabbaga, Jorge; Hoff, Paulo M

    2014-11-07

    Colorectal cancer incidence has been rising strongly in parallel with economic development. In the past few decades, much has been learned about the lifestyle, dietary and medication risk factors for this malignancy. With respect to lifestyle, compelling evidence indicates that prevention of weight gain and maintenance of a reasonable level of physical activity can positively influence in lowering the risk. Although there is controversy about the role of specific nutritional factors, consideration of dietary pattern as a whole appears useful for formulating recommendations. Though quite often recommended, the role for many supplements, including omega-3, vitamin D, folate, and vitamin B6, remains unsettled. Only calcium and vitamin D supplementation appear to add a modest benefit, particularly in those with a low daily intake. With regard to chemoprevention, medications such as aspirin and nonsteroidal anti-inflammatory drugs, and postmenopausal hormonal replacement for women might be associated with substantial reductions in colorectal cancer risk, though their utility is affected by their side effect profile. However, the role of agents such as statins, bisphosphonates and antioxidants have yet to be determined. Ultimately, primary prevention strategies focusing on modifying environmental, lifestyle risk factors, and chemopreventive drugs are options that have already been tested, and may impact on colon cancer incidence.

  19. Risk assessment and clinical decision making for colorectal cancer screening.

    Science.gov (United States)

    Schroy, Paul C; Caron, Sarah E; Sherman, Bonnie J; Heeren, Timothy C; Battaglia, Tracy A

    2015-10-01

    Shared decision making (SDM) related to test preference has been advocated as a potentially effective strategy for increasing adherence to colorectal cancer (CRC) screening, yet primary care providers (PCPs) are often reluctant to comply with patient preferences if they differ from their own. Risk stratification advanced colorectal neoplasia (ACN) provides a rational strategy for reconciling these differences. To assess the importance of risk stratification in PCP decision making related to test preference for average-risk patients and receptivity to use of an electronic risk assessment tool for ACN to facilitate SDM. Mixed methods, including qualitative key informant interviews and a cross-sectional survey. PCPs at an urban, academic safety-net institution. Screening preferences, factors influencing patient recommendations and receptivity to use of a risk stratification tool. Nine PCPs participated in interviews and 57 completed the survey. Despite an overwhelming preference for colonoscopy by 95% of respondents, patient risk (67%) and patient preferences (63%) were more influential in their decision making than patient comorbidities (31%; P decision making, yet few providers considered risk factors other than age for average-risk patients. Providers were receptive to the use of a risk assessment tool for ACN when recommending an appropriate screening test for select patients. © 2013 John Wiley & Sons Ltd.

  20. Sugars, sucrose and colorectal cancer risk: the Fukuoka colorectal cancer study.

    Science.gov (United States)

    Wang, Zhenjie; Uchida, Kazuhiro; Ohnaka, Keizo; Morita, Makiko; 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

    2014-05-01

    A diet high in sugars may promote colorectal carcinogenesis, but it remains uncertain whether high intake of sugars or sucrose confers increased risk of colorectal cancer. The authors investigated the associations of sugars and sucrose intake with colorectal cancer risk in a community-based case-control study in Japan. The study subjects comprised 816 incident cases of colorectal cancer and 815 community controls. Consumption frequencies and portion sizes of 148 food and beverage items were ascertained by a computer-assisted interview. The authors used the consumption of 29 food items to estimate sugars and sucrose intake. The odds ratios of colorectal cancer risk according to intake categories were obtained using a logistic regression model with adjustment for potential confounding variables. Overall, intakes of sugars and sucrose were not related to colorectal cancer risk either in men or women. The association between sugars intake and colorectal cancer risk differed by smoking status and alcohol use in men, but not in women. In men, sugars intake tended to be associated with colorectal cancer risk inversely among never-smokers and positively among male ever-smokers (interaction p=0.01). Sugars intake was associated with an increased risk among men with no alcohol consumption, but was unrelated to the risk among male alcohol drinkers (interaction p=0.02). Body mass index did not modify the association with sugars intake in either men or women. Sugars intake was associated with increased risk of colorectal cancer among smokers and non-alcohol drinkers in men selectively.

  1. Beclin 1 Expression is Closely Linked to Colorectal Carcinogenesis and Distant Metastasis of Colorectal Carcinoma

    Directory of Open Access Journals (Sweden)

    Mei-Ying Zhang

    2014-08-01

    Full Text Available Beclin 1 participates in development, autophagy, differentiation, anti- apoptosis, neurodegeneration, tumorigenesis and cancer progression. The roles of Beclin 1 in colorectal carcinogenesis and its subsequent progression are still unclear. Here, the mRNA and protein expression of Beclin 1 were determined in colorectal carcinoma and matched mucosa by Reverse transcriptase-polymerase chain reaction and Western blot. Immunohistochemistry and in situ hybridization (ISH were performed on tissue microarryer with colorectal carcinoma, adenoma and mucosa. The expression of Beclin 1 mRNA and protein was found to be higher in colorectal carcinoma than matched mucosa by real-time PCR and Western blot (p < 0.05. According to the ISH data, Beclin 1 expression was lower in colorectal non-neoplastic mucosa (NNM than adenoma and carcinoma (p < 0.05. Immunohistochemically, primary carcinoma showed stronger Beclin 1 expression than NNM and metastatic carcinoma in the liver (p < 0.05. Beclin 1 protein expression was negatively related to liver and distant metastasis (p < 0.05, but not correlated with age, sex, depth of invasion, lymphatic or venous invasion, lymph node metastasis, tumor-node-metastasis (TNM staging, differentiation or serum carcinoembryonic antigen (CEA concentration (p > 0.05. Survival analysis indicated that Beclin 1 expression was not linked to favorable prognosis of the patients with colorectal carcinoma (p > 0.05. Cox’s model indicated that depth of invasion and distant metastasis were independent prognostic factors for colorectal carcinomas (p < 0.05. It was suggested that Beclin 1 expression is closely linked to colorectal carcinogenesis and distant metastasis of colorectal carcinoma.

  2. Repeat polymorphisms in ESR2 and AR and colorectal cancer risk and prognosis: results from a German population-based case-control study.

    Science.gov (United States)

    Rudolph, Anja; Shi, Hong; Försti, Asta; Hoffmeister, Michael; Sainz, Juan; Jansen, Lina; Hemminki, Kari; Brenner, Hermann; Chang-Claude, Jenny

    2014-11-07

    Evidence has accumulated which suggests that sex steroids influence colorectal cancer development and progression. We therefore assessed the association of repeat polymorphisms in the estrogen receptor β gene (ESR2) and the androgen receptor gene (AR) with colorectal cancer risk and prognosis. The ESR2 CA and AR CAG repeat polymorphisms were genotyped in 1798 cases (746 female, 1052 male) and 1810 controls (732 female, 1078 male), matched for sex, age and county of residence. Colorectal cancer risk associations overall and specific for gender were evaluated using multivariate logistic regression models adjusted for sex, county of residence and age. Associations with overall and disease-specific survival were evaluated using Cox proportional hazard models adjusted for established prognostic factors (diagnosis of other cancer after colorectal cancer diagnosis, detection by screening, treatment with adjuvant chemotherapy, tumour extent, nodal status, distant metastasis, body mass index, age at diagnosis and year of diagnosis) and stratified for grade of differentiation. Heterogeneity in gender specific associations was assessed by comparing models with and without a multiplicative interaction term by means of a likelihood ratio test. The average number of ESR2 CA repeats was associated with a small 5% increase in colorectal cancer risk (OR = 1.05, 95% CI 1.01-1.10) without significant heterogeneity according to gender or tumoural ESR2 expression. We found no indication for an association between the AR CAG repeat polymorphisms and risk of colorectal cancer. The ESR2 CA and AR CAG repeat polymorphisms were not associated with overall survival or disease specific survival after colorectal cancer diagnosis. Higher numbers of ESR2 CA repeats are potentially associated with a small increase in colorectal cancer risk. Our study does not support an association between colorectal cancer prognosis and the investigated repeat polymorphisms.

  3. Do Physician Recommendations for Colorectal Cancer Screening Differ by Patient Age?

    Directory of Open Access Journals (Sweden)

    Maida J Sewitch

    2007-01-01

    Full Text Available Colorectal cancer screening is underutilized, resulting in preventable morbidity and mortality. In the present study, age-related and other disparities associated with physicians’ delivery of colorectal cancer screening recommendations were examined. The present cross-sectional study included 43 physicians and 618 of their patients, aged 50 to 80 years, without past or present colorectal cancer. Of the 285 screen-eligible patients, 45% received a recommendation. Multivariate analyses revealed that, compared with younger nonde-pressed patients, older depressed patients were less likely to receive fecal occult blood test recommendations, compared with no recommendation (OR=0.31, 95% CI 0.09 to 1.02, as well as less likely to receive colonoscopy recommendations, compared with no recommendation (OR=0.14; 95% CI 0.03 to 0.66. Comorbidity and marital status were associated with delivery of fecal occult blood test and colonoscopy recommendations, respectively, compared with no recommendation. In summary, patient age and other characteristics appeared to influence physicians’ delivery of colorectal cancer screening and choice of modality.

  4. An apple oligogalactan potentiates the growth inhibitory effect of celecoxib on colorectal cancer.

    Science.gov (United States)

    Li, Yuhua; Niu, Yinbo; Sun, Yang; Mei, Lin; Zhang, Bangle; Li, Qian; Liu, Li; Zhang, Rong; Chen, Jianfa; Mei, Qibing

    2014-01-01

    Multiple studies have indicated that selective cyclooxygenase-2 (COX-2) inhibitors possess clinically chemopreventive and preclinically anticancer activities. Their long-term use, however, may be limited by the cardiovascular toxicity. This study tried to investigate whether an apple oligogalactan (AOG) could enhance the growth inhibitory effect of celecoxib on colorectal cancer. Caco-2 and HT-29 cell lines were exposed to different concentrations of AOG (0-1 g/L), celecoxib (0-25 μmol/L), and their combination. COX-2 levels were assessed by reverse transcription PCR and Western blot. COX-2 activity was evaluated by measuring prostaglandin E2 concentration. A colitis-associated colorectal cancer (CACC) mouse model was used to determine the effect of the combination in vivo. AOG (0.1-0.5 g/L) could potentiate the inhibitory effect of physiologic doses of celecoxib (5 μmol/L) on cell growth and decrease COX-2 expressions both at RNA and protein levels. In vivo, the combination (2.5% AOG plus 0.04% celecoxib, w/w) prevented against CACC in mice effectively. Our data indicate that AOG could potentiate the growth inhibitory effect of celecoxib on colorectal cancer both in vitro and in vivo through influencing the expression and function of COX-2 and phosphorylation of MAPKs, which suggests a new possible combinatorial strategy in colorectal cancer therapy.

  5. Low priority main reason not to participate in a colorectal cancer screening program with a faecal occult blood test

    NARCIS (Netherlands)

    van Rijn, A. F.; van Rossum, L. G. M.; Deutekom, M.; Laheij, R. J. F.; Fockens, P.; Bossuyt, P. M. M.; Dekker, E.; Jansen, J. B. M. J.

    2008-01-01

    Compared with screening programs for breast and cervical cancer, reported participation rates for colorectal cancer (CRC) screening are low. The effectiveness of a screening program is strongly influenced by the participation rate. The aim of this study was to investigate the main reasons not to

  6. Low priority main reason not to participate in a colorectal cancer screening program with a faecal occult blood test.

    NARCIS (Netherlands)

    Rijn, A.F. van; Rossum, L.G.M. van; Deutekom, M.; Laheij, R.J.F.; Fockens, P.; Bossuyt, P.M.; Dekker, E. den; Jansen, J.B.M.J.

    2008-01-01

    BACKGROUND: Compared with screening programs for breast and cervical cancer, reported participation rates for colorectal cancer (CRC) screening are low. The effectiveness of a screening program is strongly influenced by the participation rate. The aim of this study was to investigate the main

  7. Associations of dietary methyl donor intake with MLH1 promoter hypermethylation and related molecular phenotypes in sporadic colorectal cancer

    NARCIS (Netherlands)

    Vogel, S. de; Bongaerts, B.W.C.; Wouters, K.A.D.; Kester, A.D.M.; Schouten, L.J.; Goeij, A.F.P.M. de; Bruïne, A.P. de; Goldbohm, R.A.; Brandt, P.A. van den; Engeland, M. van; Weijenberg, M.P.

    2008-01-01

    Intake of dietary factors that serve as methyl group donors may influence promoter hypermethylation in colorectal carcinogenesis. We investigated whether dietary folate, vitamin B2 and vitamin B6, methionine and alcohol were associated with mutL homologue 1 (MLH1) hypermethylation and the related

  8. Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations

    NARCIS (Netherlands)

    Fehringer, Gordon; Kraft, Peter; Pharoah, Paul D.; Eeles, Rosalind A.; Chatterjee, Nilanjan; Schumacher, Fredrick R.; Schildkraut, Joellen M.; Lindstrom, Sara; Brennan, Paul; Bickeboller, Heike; Houlston, Richard S.; Landi, Maria Teresa; Caporaso, Neil; Risch, Angela; Al Olama, Ali Amin; Berndt, Sonja I.; Giovannucci, Edward L.; Gronberg, Henrik; Kote-Jarai, Zsofia; Ma, Jing; Muir, Kenneth; Stampfer, Meir J.; Stevens, Victoria L.; Wiklund, Fredrik; Willett, Walter C.; Goode, Ellen L.; Permuth, Jennifer B.; Risch, Harvey A.; Reid, Brett M.; Bezieau, Stephane; Brenner, Hermann; Chan, Andrew T.; Chang-Claude, Jenny; Hudson, Thomas J.; Kocarnik, Jonathan K.; Newcomb, Polly A.; Schoen, Robert E.; Slattery, Martha L.; White, Emily; Adank, Muriel A.; Ahsan, Habibul; Aittomaki, Kristiina; Baglietto, Laura; Blomquist, Carl; Canzian, Federico; Czene, Kamila; dos-Santos-Silva, Isabel; Eliassen, A. Heather; Figueroa, Jonine D.; Timens, Wim

    2016-01-01

    Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820

  9. Cross-cancer genome-wide analysis of lung, ovary, breast, prostate, and colorectal cancer reveals novel pleiotropic associations

    NARCIS (Netherlands)

    Fehringer, G. (Gordon); P. Kraft (Peter); P.D.P. Pharoah (Paul); R. Eeles (Rosalind); Chatterjee, N. (Nilanjan); F.R. Schumacher (Fredrick R); J.M. Schildkraut (Joellen); S. Lindstrom (Stephen); P. Brennan (Paul); H. Bickeböller (Heike); R. Houlston (Richard); M.T. Landi (Maria Teresa); N.E. Caporaso (Neil); Risch, A. (Angela); A.A. Al Olama (Ali Amin); S.I. Berndt (Sonja); Giovannucci, E.L. (Edward L.); H. Grönberg (Henrik); Z. Kote-Jarai; Ma, J. (Jing); K.R. Muir (K.); M.J. Stampfer (Meir J.); Stevens, V.L. (Victoria L.); F. Wiklund (Fredrik); W.C. Willett (Walter C.); E.L. Goode (Ellen); Permuth, J.B. (Jennifer B.); H. Risch (Harvey); Reid, B.M. (Brett M.); Bezieau, S. (Stephane); H. Brenner (Hermann); Chan, A.T. (Andrew T.); J. Chang-Claude (Jenny); T.J. Hudson (Thomas); Kocarnik, J.K. (Jonathan K.); P. Newcomb (Polly); Schoen, R.E. (Robert E.); Slattery, M.L. (Martha L.); White, E. (Emily); M.A. Adank (Muriel); H. Ahsan (Habibul); K. Aittomäki (Kristiina); Baglietto, L. (Laura); Blomquist, C. (Carl); F. Canzian (Federico); K. Czene (Kamila); I. dos Santos Silva (Isabel); Eliassen, A.H. (A. Heather); J.D. Figueroa (Jonine); D. Flesch-Janys (Dieter); O. Fletcher (Olivia); M. García-Closas (Montserrat); M.M. Gaudet (Mia); Johnson, N. (Nichola); P. Hall (Per); A. Hazra (Aditi); R. Hein (Rebecca); Hofman, A. (Albert); J.L. Hopper (John); A. Irwanto (Astrid); M. Johansson (Mattias); R. Kaaks (Rudolf); M.G. Kibriya (Muhammad); P. Lichtner (Peter); J. Liu (Jianjun); E. Lund (Eiliv); Makalic, E. (Enes); A. Meindl (Alfons); B. Müller-Myhsok (B.); Muranen, T.A. (Taru A.); H. Nevanlinna (Heli); P.H.M. Peeters; J. Peto (Julian); R. Prentice (Ross); N. Rahman (Nazneen); M.-J. Sanchez (Maria-Jose); D.F. Schmidt (Daniel); R.K. Schmutzler (Rita); M.C. Southey (Melissa); Tamimi, R. (Rulla); S.P.L. Travis (Simon); C. Turnbull (Clare); Uitterlinden, A.G. (Andre G.); Z. Wang (Zhaoming); A.S. Whittemore (Alice); X.R. Yang (Xiaohong); W. Zheng (Wei); D. Buchanan (Daniel); G. Casey (Graham); G. Conti (Giario); C.K. Edlund (Christopher); S. Gallinger (Steve); R. Haile (Robert); M. Jenkins (Mark); Marchand, L. (Loïcle); Li, L. (Li); N.M. Lindor (Noralane); Schmit, S.L. (Stephanie L.); S.N. Thibodeau (Stephen); M.O. Woods (Michael); T. Rafnar (Thorunn); J. Gudmundsson (Julius); S.N. Stacey (Simon); Stefansson, K. (Kari); P. Sulem (Patrick); Chen, Y.A. (Y. Ann); J.P. Tyrer (Jonathan); Christiani, D.C. (David C.); Wei, Y. (Yongyue); H. Shen (Hongbing); Z. Hu (Zhibin); X.-O. Shu (Xiao-Ou); Shiraishi, K. (Kouya); A. Takahashi (Atsushi); Y. Bossé (Yohan); M. Obeidat (Ma'en); D.C. Nickle (David); W. Timens (Wim); M. Freedman (Matthew); Li, Q. (Qiyuan); D. Seminara (Daniela); S.J. Chanock (Stephen); Gong, J. (Jian); U. Peters (Ulrike); S.B. Gruber (Stephen); Amos, C.I. (Christopher I.); T.A. Sellers (Thomas A.); D.F. Easton (Douglas F.); D. Hunter (David); C.A. Haiman (Christopher A.); B.E. Henderson (Brian); R.J. Hung (Rayjean)

    2016-01-01

    textabstractIdentifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851

  10. Cross-cancer genome-wide analysis of lung, ovary, breast, prostate, and colorectal cancer reveals novel pleiotropic associations

    NARCIS (Netherlands)

    Fehringer, Gordon; Kraft, Peter; Pharoah, Paul D.; Eeles, Rosalind A.; Chatterjee, Nilanjan; Schumacher, Fredrick R.; Schildkraut, Joellen M.; Lindström, Sara; Brennan, Paul; Bickeböller, Heike; Houlston, Richard S.; Landi, Maria Teresa; Caporaso, Neil; Risch, Angela; Al Olama, Ali Amin; Berndt, Sonja I.; Giovannucci, Edward L.; Grönberg, Henrik; Kote-Jarai, Zsofia; Ma, Jing; Muir, Kenneth; Stampfer, Meir J.; Stevens, Victoria L.; Wiklund, Fredrik; Willett, Walter C.; Goode, Ellen L.; Permuth, Jennifer B.; Risch, Harvey A.; Reid, Brett M.; Bezieau, Stephane; Brenner, Hermann; Chan, Andrew T.; Chang-Claude, Jenny; Hudson, Thomas J.; Kocarnik, Jonathan K.; Newcomb, Polly A.; Schoen, Robert E.; Slattery, Martha L.; White, Emily; Adank, Muriel A.; Ahsan, Habibul; Aittomäki, Kristiina; Baglietto, Laura; Blomquist, Carl; Canzian, Federico; Czene, Kamila; Dos-Santos-silva, Isabel; Eliassen, A. Heather; Figueroa, Jonine D.; Flesch-Janys, Dieter; Fletcher, Olivia; Garcia-Closas, Montserrat; Gaudet, Mia M.; Johnson, Nichola; Hall, Per; Hazra, Aditi; Hein, Rebecca; Hofman, Albert; Hopper, John L.; Irwanto, Astrid; Johansson, Mattias; Kaaks, Rudolf; Kibriya, Muhammad G.; Lichtner, Peter; Liu, Jianjun; Lund, Eiliv; Makalic, Enes; Meindl, Alfons; Müller-Myhsok, Bertram; Muranen, Taru A.; Nevanlinna, Heli; Peeters, Petra H.; Peto, Julian; Prentice, Ross L.; Rahman, Nazneen; Sanchez, Maria Jose; Schmidt, Daniel F.; Schmutzler, Rita K.; Southey, Melissa C.; Tamimi, Rulla; Travis, Ruth C.; Turnbull, Clare; Uitterlinden, Andre G.; Wang, Zhaoming; Whittemore, Alice S.; Yang, Xiaohong R.; Zheng, Wei; Buchanan, Daniel D.; Casey, Graham; Conti, David V.; Edlund, Christopher K.; Gallinger, Steven; Haile, Robert W.; Jenkins, Mark; Marchand, Loïcle; Li, Li; Lindor, Noralene M.; Schmit, Stephanie L.; Thibodeau, Stephen N.; Woods, Michael O.; Rafnar, Thorunn; Gudmundsson, Julius; Stacey, Simon N.; Stefansson, Kari; Sulem, Patrick; Chen, Y. Ann; Tyrer, Jonathan P.; Christiani, David C.; Wei, Yongyue; Shen, Hongbing; Hu, Zhibin; Shu, Xiao Ou; Shiraishi, Kouya; Takahashi, Atsushi; Bossé, Yohan; Obeidat, Ma'en; Nickle, David; Timens, Wim; Freedman, Matthew L.; Li, Qiyuan; Seminara, Daniela; Chanock, Stephen J.; Gong, Jian; Peters, Ulrike; Gruber, Stephen B.; Amos, Christopher I.; Sellers, Thomas A.; Easton, Douglas F.; Hunter, David J.; Haiman, Christopher A.; Henderson, Brian E.; Hung, Rayjean J.

    2016-01-01

    Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820

  11. Body size, physical activity and risk of colorectal cancer with or without the CpG island methylator phenotype (CIMP)

    NARCIS (Netherlands)

    Hughes, L.A.E.; Simons, C.C.J.M.; Brandt, P.A. van den; Goldbohm, R.A.; Goeij, A.F. de; Bruïne, A.P. de; Engeland, M. van; Weijenberg, M.P.

    2011-01-01

    Background: We investigated how body size and physical activity influence the risk of the CpG island methylator phenotype (CIMP) in colorectal cancer (CRC). Methods: In the Netherlands Cohort Study (n = 120,852), risk factors were self-reported at baseline in 1986. After 7.3 years of follow-up, 603

  12. 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.

  13. 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.

  14. Intraoperative ultrasound in colorectal surgery.

    Science.gov (United States)

    Greif, Franklin; Aranovich, David; Hananel, Nissim; Knizhnik, Mikhail; Belenky, Alexander

    2009-09-01

    To assess the accuracy of intraoperative ultrasound (IOUS) as a localizing technique for colorectal resections, and its impact on surgical management. Twenty-five patients (15 men and 10 women; mean age, 74.4 years) with early cancers (p T1), or polyps, not amenable to endoscopic removal were selected. IOUS was used as a sole method of intraoperative localization. Its performance was evaluated through review of preoperative colonoscopy reports, intraoperative findings, histopathology reports, and clinical follow-up. The lesions were situated in the cecum (n = 5), ascending colon (n = 3), transverse colon (n = 4), descending colon (n = 7), and rectum (n = 6). IOUS technique allowed correct localization in 24 of 25 patients, visualization of the bowel wall, and its penetration by malignant tumors. In rectal lesions, IOUS showed clearly the tumor and its margin, which facilitated performance sphincter-sparing procedure. In patients with small polyps and early cancers of colon and rectum, IOUS may be effectively used as a sole method of intraoperative localization and provide additional information that may alter decision making with regard to surgical technique. (c) 2009 Wiley Periodicals, Inc.

  15. 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.

  16. Epigenetics and colorectal cancer pathogenesis.

    Science.gov (United States)

    Bardhan, Kankana; Liu, Kebin

    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.

  17. Epigenetics and Colorectal Cancer Pathogenesis

    International Nuclear Information System (INIS)

    Bardhan, Kankana; Liu, Kebin

    2013-01-01

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

  18. Epigenetics and Colorectal Cancer Pathogenesis

    Directory of Open Access Journals (Sweden)

    Kebin Liu

    2013-06-01

    Full Text Available 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.

  19. CysLT(1)R antagonists inhibit tumor growth in a xenograft model of colon cancer.

    Science.gov (United States)

    Savari, Sayeh; Liu, Minghui; Zhang, Yuan; Sime, Wondossen; Sjölander, Anita

    2013-01-01

    The expression of the inflammatory G-protein coupled receptor CysLT1R has been shown to be upregulated in colon cancer patients and associated with poor prognosis. The present study investigated the correlation between CysLT1R and colon cancer development in vivo using CysLT1R antagonists (ZM198,615 or Montelukast) and the nude mouse xenograft model. Two drug administration regimens were established. The first regimen was established to investigate the importance of CysLT1R in tumor initiation. Nude mice were inoculated with 50 µM CysLT1R antagonist-pretreated HCT-116 colon cancer cells and received continued treatment (5 mg/kg/day, intraperitoneally). The second regimen aimed to address the role of CysLT1R in tumor progression. Nude mice were inoculated with non-pretreated HCT-116 cells and did not receive CysLT1R antagonist treatment until recordable tumor appearance. Both regimens resulted in significantly reduced tumor size, attributed to changes in proliferation and apoptosis as determined by reduced Ki-67 levels and increased levels of p21(WAF/Cip1) (Pcolon cancer cell line HCT-116 and CysLT1R antagonists. In addition to significant reductions in cell proliferation, adhesion and colony formation, we observed induction of cell cycle arrest and apoptosis in a dose-dependent manner. The ability of Montelukast to inhibit growth of human colon cancer xenograft was further validated by using two additional colon cancer cell lines, SW-480 and HT-29. Our results demonstrate that CysLT1R antagonists inhibit growth of colon cancer xenografts primarily by reducing proliferation and inducing apoptosis of the tumor cells.

  20. The effects of a picosecond pulsed electric field on angiogenesis in the cervical cancer xenograft models.

    Science.gov (United States)

    Wu, Limei; Yao, Chenguo; Xiong, Zhengai; Zhang, Ruizhe; Wang, Zhiliang; Wu, Yutong; Qin, Qin; Hua, Yuanyuan

    2016-04-01

    The application of picosecond pulsed electric field (psPEF) is a new biomedical engineering technique used in cancer therapy. However, its effects on cervical cancer angiogenesis are not clear. Therefore, the aim of the present study is to investigate the effects of psPEF on angiogenesis in cervical cancer xenograft models. Xenograft tumors were created by subcutaneously inoculating nude mice (athymic BALB/c nu/nu mice) with HeLa cells, then were placed closely between tweezer-type plate electrodes and subjected to psPEF with a gradually increased electric field intensity (0kV/cm, 50kV/cm, 60kV/cm, 70kV/cm). The direct effect on tumor tissue was observed by hematoxylin and eosin (H&E) staining and transmission electron microscopy (TEM). The changes of blood vessels and oxygen saturation (sO2) of tumors were monitored in vivo by photoacoustic tomography (PAT). The microvessel density (MVD), vascular endothelial growth factor (VEGF) and hypoxia-inducible transcription factors (HIF-1α and HIF-2α) were detected by immunohistochemical technique (IHC). Their protein expressions and gene transcription levels were evaluated using western blot (WB) and quantitative reverse transcription and polymerase chain reaction (RT-PCR). PsPEF induced obvious necrosis of cervical cancer tissue; with the increasing of electric field intensity, the MVD, vascular PA signal and sO2 values declined significantly. The protein expression and gene transcription levels of VEGF, HIF1α and HIF2α were significantly decreased at the same time. PsPEF exhibited dramatic anti-tumor and anti-angiogenesis effects in cervical cancer xenograft models by exerting direct effect on cancer cells and vascular endothelial cells and indirect effect on tumor angiogenesis-related factors. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Survivin inhibitor YM155 suppresses gastric cancer xenograft growth in mice without affecting normal tissues.

    Science.gov (United States)

    Cheng, Xiao Jiao; Lin, Jia Cheng; Ding, Yan Fei; Zhu, Liming; Ye, Jing; Tu, Shui Ping

    2016-02-09

    Survivin overexpression is associated with poor prognosis of human gastric cancer, and is a target for gastric cancer therapy. YM155 is originally identified as a specific inhibitor of survivin. In this study, we investigated the antitumor effect of YM155 on human gastric cancer. Our results showed that YM155 treatment significantly inhibited cell proliferation, reduced colony formation and induced apoptosis of gastric cancer cells in a dose-dependent manner. Accordingly, YM155 treatment significantly decreased survivin expression without affecting XIAP expression and increased the cleavage of apoptosis-associated proteins caspase 3, 7, 8, 9. YM155 significantly inhibited sphere formation of gastric cancer cells, suppressed expansion and growth of the formed spheres (cancer stem cell-like cells, CSCs) and downregulated the protein levels of β-catenin, c-Myc, Cyclin D1 and CD44 in gastric cancer cells. YM155 infusion at 5 mg/kg/day for 7 days markedly inhibited growth of gastric cancer xenograft in a nude mouse model. Immunohistochemistry staining and Western Blot showed that YM155 treatment inhibited expression of survivin and CD44, induced apoptosis and reduced CD44+ CSCs in xenograft tumor tissues in vivo. No obvious pathological changes were observed in organs (e.g. heart, liver, lung and kidney) in YM155-treated mice. Our results demonstrated that YM155 inhibits cell proliferation, induces cell apoptosis, reduces cancer stem cell expansion, and inhibits xenograft tumor growth in gastric cancer cells. Our results elucidate a new mechanism by which YM155 inhibits gastric cancer growth by inhibition of CSCs. YM155 may be a promising agent for gastric cancer treatment.

  2. Initial experience with xenograft bioconduit for the treatment of complex prosthetic valve endocarditis.

    Science.gov (United States)

    Roubelakis, Apostolos; Karangelis, Dimos; Sadeque, Syed; Yanagawa, Bobby; Modi, Amit; Barlow, Clifford W; Livesey, Steven A; Ohri, Sunil K

    2017-07-01

    The treatment of complex prosthetic valve endocarditis (PVE) with aortic root abscess remains a surgical challenge. Several studies support the use of biological tissues to minimize the risk of recurrent infection. We present our initial surgical experience with the use of an aortic xenograft conduit for aortic valve and root replacement. Between October 2013 and August 2015, 15 xenograft bioconduits were implanted for complex PVE with abscess (13.3% female). In 6 patients, concomitant procedures were performed: coronary bypass (n=1), mitral valve replacement (n=5) and tricuspid annuloplasty (n=1). The mean age at operation was 60.3±15.5 years. The mean Logistic European system for cardiac operating risk evaluation (EuroSCORE) was 46.6±23.6. The median follow-up time was 607±328 days (range: 172-1074 days). There were two in-hospital deaths (14.3% mortality), two strokes (14.3%) and seven patients required permanent pacemaker insertion for conduction abnormalities (46.7%). The mean length of hospital stay was 26 days. At pre-discharge echocardiography, the conduit mean gradient was 9.3±3.3mmHg and there was either none (n=6), trace (n=6) or mild aortic insufficiency (n=1). There was no incidence of mid-term death, prosthesis-related complications or recurrent endocarditis. Xenograft bioconduits may be safe and effective for aortic valve and root replacement for complex PVE with aortic root abscess. Although excess early mortality reflects the complexity of the patient population, there was good valve hemodynamics, with no incidence of recurrent endocarditis or prosthesis failure in the mid-term. Our data support the continued use and evaluation of this biological prosthesis in this high-risk patient cohort.

  3. 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

  4. 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.

  5. 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

  6. Management of colorectal trauma: a review.

    Science.gov (United States)

    Cheong, Ju Yong; Keshava, Anil

    2017-07-01

    Traumatic colorectal injuries are common during times of military conflict, and major improvements in their care have arisen in such periods. Since World War II, many classification systems for colorectal trauma have been proposed, including (i) Flint Grading System; (ii) Penetrating Abdominal Trauma Index; (iii) Colonic/Rectal Injury Scale; and (iv) destructive/non-destructive colonic injuries. The primary goal of these classifications was to aid surgical management and, more particularly, to determine whether a primary repair or faecal diversion should be performed. Primary repair is now the preferred surgical option. Patients who have been identified as having destructive injuries have been found to have higher anastomotic leak rates after a primary repair. Damage control principles need to be adhered to in surgical decision-making. In this review, we discuss the mechanisms of injury, classifications, clinical presentation and current recommendations for the management of colorectal trauma. © 2017 Royal Australasian College of Surgeons.

  7. Linking Gut Microbiota to Colorectal Cancer

    DEFF Research Database (Denmark)

    Raskov, Hans; Burcharth, Jakob; Pommergaard, Hans-Christian

    2017-01-01

    Pre-clinical and clinical data produce mounting evidence that the microbiota is strongly associated with colorectal carcinogenesis. Dysbiosis may change the course of carcinogenesis as microbial actions seem to impact genetic and epigenetic alterations leading to dysplasia, clonal expansion...... and malignant transformation. Initiation and promotion of colorectal cancer may result from direct bacterial actions, bacterial metabolites and inflammatory pathways. Newer aspects of microbiota and colorectal cancer include quorum sensing, biofilm formation, sidedness and effects/countereffects of microbiota...... and probiotics on chemotherapy. In the future, targeting the microbiota will probably be a powerful weapon in the battle against CRC as gut microbiology, genomics and metabolomics promise to uncover important linkages between microbiota and intestinal health....

  8. Enhanced replication of attenuated HSV-1 in irradiated human glioma xenografts

    International Nuclear Information System (INIS)

    Advani, Sunil J.; Kataoka, Yasushi; Sibley, Greg S.; Song, Paul Y.; Hallahan, Dennis E.; Roizman, Bernard; Weichselbaum, Ralph R.

    1997-01-01

    Purpose: Previously we had shown that combining ionizing radiation (IR) with attenuated replication competent HSV-1 (R3616) significantly increased glioma xenograft eradication compared to IR or virus alone. One hypothesis is that IR induces cell factors that contribute to augment viral replication thereby increasing the efficacy of attenuated HSV-1. The purpose of this study was to examine if IR altered viral replication of attenuated HSV-1 in glioma xenografts Material and Methods: Human U-87MG glioma cells were grown in the hindlimb of athymic mice and grown to >200 mm 3 . Tumors were infected with 2x10 7 plaque forming units (pfu) of R3616 ( γ1 34.5 - ) or R7020 (multimutated, γ1 34.5 + ) on day 0 and irradiated with 20 Gy on day 1 and 25 Gy on day 2. Tumors were harvested 3, 5, 7, and 14 days after viral injection. Tumors were homogenized and sonnicated. Serial dilutions of tumor extract were overlaid on Vero cells to determine the number of pfu. In addition, in-situ hybridization to HSV-1 DNA was performed on tumors harvested at day 7. Results: In-situ hybridization revealed larger numbers of glial cells infected with HSV along with a greater distribution in the irradiated tumors compared to non-irradiated tumors. We next quantified viral particles in infected tumors +/- IR: Conclusion: Herein we demonstrate radiation enhanced viral replication as one of the interactive effects of combining IR and attenuated HSV in treating glioma xenografts and a potential therapeutic motif in the treatment of gliomas. To reduce normal tissue toxicity of HSV in glioma therapy, viruses must be attenuated. However, attenuating the virus compromises its replication and thus its potential efficacy. Our results indicate that IR augments the amount of virus recovered from human glioma xenografts for up to 3 days post IR. The results do not appear to be related to a specific mutation in the herpes genome but rather to herpes viruses in general. Yields of R7020 were greater than R

  9. Patient Derived Xenograft Models: An Emerging Platform for Translational Cancer Research

    Science.gov (United States)

    Hidalgo, Manuel; Amant, Frederic; Biankin, Andrew V.; Budinská, Eva; Byrne, Annette T.; Caldas, Carlos; Clarke, Robert B.; de Jong, Steven; Jonkers, Jos; Mælandsmo, Gunhild Mari; Roman-Roman, Sergio; Seoane, Joan; Trusolino, Livio; Villanueva, Alberto

    2014-01-01

    Recently, there has been increasing interest in the development and characterization of patient derived tumor xenograft (PDX) models for cancer research. PDX models mostly retain the principal histological and genetic characteristics of their donor tumor and remain stable across passages. These models have been shown to be predictive of clinical outcomes and are being used for preclinical drug evaluation, biomarker identification, biological studies, and personalized medicine strategies. This paper summarizes the current state of the art in this field including methodological issues, available collections, practical applications, challenges and shortcoming, and future directions, and introduces a European consortium of PDX models. PMID:25185190

  10. Stimulation of osteoblast activity by induction of Aloe vera and xenograft combination

    Directory of Open Access Journals (Sweden)

    Utari Kresnoadi

    2011-12-01

    Full Text Available Background: Tooth extraction is generally followed by alveolar ridge resorption that later can cause flat ridge. Aloe vera have biogenic stimulator and hormone activities for wound healing. Purpose: This study was aimed to know osteoblast activities in alveolar bone after induction of Aloe vera and XCB combination. Methods: Fifty four of Cavia cabaya were divided into three main groups. Group I was control group. Group II was filled with xenograft concelous bovine (XCB and group III was filled with the combination of Aloe vera gel and XCB. Then, each group was divided into three sub groups according to timing, they are 14, 30, and 60 days after tooth extraction and application. Histology and morphology examination were performed on the harvested specimens. Results: There were significant differences between the control group and the other groups filled with the combination of Aloe vera and XCB. Conclusion: In conclusion, the application of Aloe vera gel and xenograft combination decrease the number of osteoclast and increase the number of osteoblast in post tooth extraction alveolar bone structure indicating the new growth of alveolar bone.Latar belakang: Pencabutan gigi pada umumnya selalu diikuti resopsi tulang alveolar, sehingga bila terjadi dalam waktu yang lama ridge akan menjadi flat. Aloe vera adalah bahan stimulasi biogenik dan mempunyai aktivitas hormon untuk proses penyembuhan luka. Tujuan: Tujuan dari penelitian ini adalah untuk mengetahui aktivitas osteoblas pada tulang alveol dengan pemberian kombinasi Aloe vera gel dan xenograft concelous bovine (XCB. Metode: Lima puluh empat ekor Cavia cabaya, dibagi menjadi 3 kelompok besar, kelompok pertama adalah kelompok kontrol yaitu hanya dilakukan pencabutan saja tanpa perlakuan, kelompok ke-2 yaitu kelompok yang setelah dicabut diberi XCB saja dan kelompok ke-3 yaitu kelompok yang setelah pencabutan diberi kombinasi Aloe vera gel dengan XCB pada luka bekas pencabutan gigi. Kemudian masing

  11. Interpretive conundrum on the exclusion criterion of "transplantation with xenografts" for tissue and cell donation.

    Science.gov (United States)

    Cox, Michael A; Brubaker, Scott A

    2012-06-01

    In the context of the EU Directives for human tissues and cells (2004/23/EC, 2006/17/EC and 2006/86/EC) further interest has arisen on the practical application of a few clauses. One such aspect, for the evaluation phase of a potential donor, is the interpretation of the exclusion criterion "transplantation with xenografts." This article outlines the consensus viewpoints regarding the earlier evaluation of the risks related to xenotransplantation and describes the current status of the terminology and recommendations/laws in several healthcare sectors. The application of uniform terminology is encouraged within the healthcare sectors at the international level.

  12. Concurrent Longitudinal EPR Monitoring of Tissue Oxygenation, Acidosis, and Reducing Capacity in Mouse Xenograft Tumor Models.

    Science.gov (United States)

    Bobko, Andrey A; Evans, Jason; Denko, Nicholas C; Khramtsov, Valery V

    2017-06-01

    Tissue oxygenation, extracellular acidity, and tissue reducing capacity are among crucial parameters of tumor microenvironment (TME) of significant importance for tumor pathophysiology. In this paper, we demonstrate the complementary application of particulate lithium octa-n-butoxy-naphthalocyanine and soluble nitroxide paramagnetic probes for monitoring of these TME parameters using electron paramagnetic resonance (EPR) technique. Two different types of therapeutic interventions were studied: hypothermia and systemic administration of metabolically active drug. In summary, the results demonstrate the utility of EPR technique for non-invasive concurrent longitudinal monitoring of physiologically relevant chemical parameters of TME in mouse xenograft tumor models, including that under therapeutic intervention.

  13. Analyzing the mechanisms of cell killing by ionizing radiation in monolayer, spheroids and xenografted tumours

    International Nuclear Information System (INIS)

    Horas, J.A.; Olguín, O.R.; Rizzotto, M.G.

    2017-01-01

    A relationship between oxygen enhancement ratio (OER) and parameters of Linear Quadratic (LQ) model in hypoxic and aerobic conditions in several cell lines grown as monolayer, spheroids and transplanted tumors (xenograft) is tested. By considering this relationship, the two mechanisms of cell death by radiation appear. Surviving Fraction (SF) fits are compared in both oxygenation conditions by using the LQ. The data are obtained from literature. The existence of such mechanisms and their implications in the different systems studied is shown. The validity of one or other mechanism in each case is determined and the OER dependence with dose. (authors) [es

  14. Expressions of Machismo in Colorectal Cancer Screening Among New Mexico Hispanic Subpopulations

    OpenAIRE

    Getrich, Christina M.; Sussman, Andrew L.; Helitzer, Deborah L.; Hoffman, Richard M.; Warner, Teddy D.; Sánchez, Victoria; Solares, Angélica; Rhyne, Robert L.

    2011-01-01

    Although national colorectal cancer (CRC) incidence rates have steadily decreased, the rate for New Mexico Hispanics has been increasing and screening rates are low. We conducted an exploratory qualitative study to determine barriers to CRC screening for New Mexico Hispanics. We found that machismo served as a dynamic influence on men’s health seeking behaviors; however, it was conceptualized differently by two distinct Hispanic subpopulations and therefore appeared to play a different role i...

  15. Korean Guidelines for Colorectal Cancer Screening and Polyp Detection

    International Nuclear Information System (INIS)

    Lee, Bo In; Hong, Sung Pil; Kim, Seong Eun

    2012-01-01

    Colorectal cancer is currently the second most common cancer among Korean males and the fourth most common among females. Since the majority of colorectal cancer case present following the prolonged transformation of adenomas into carcinomas, early detection and removal of colorectal adenomas are vital methods in its prevention. Considering the increasing incidence of colorectal cancer and polyps in Korea, it is very important to establish national guidelines for colorectal cancer screening and polyp detection. The proposed guidelines have been developed by the Korean Multi-Society Task Force using evidence-based methods. Systematic reviews and meta-analyses have been used to form the statements contained in the guidelines. This paper discusses the epidemiology of colorectal cancers and adenomas in Korea as well as optimal methods for screening of colorectal cancer and detection of adenomas including fecal occult blood tests, radiologic tests, and endoscopic examinations.

  16. Colorectal carcinogenesis-update and perspectives

    DEFF Research Database (Denmark)

    Raskov, Hans; Pommergaard, Hans-Christian; Burcharth, Jakob

    2014-01-01

    Colorectal cancer (CRC) is a very common malignancy in the Western World and despite advances in surgery, chemotherapy and screening, it is still the second leading cause of cancer deaths in this part of the world. Numerous factors are found important in the development of CRC including colonocyte....... To identify early cancers, screening programs have been initiated, and the leading strategy has been the use of faecal occult blood testing followed by colonoscopy in positive cases. Regarding the treatment of colorectal cancer, significant advances have been made in the recent decade. The molecular targets...

  17. 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.

  18. Malnutrition In Patients With Colorectal Carcinoma (Oncologist's Point Of View); Problematika malnutricie u pacientov s kolorektalnym karcinomom (z pohladu onkologa)

    Energy Technology Data Exchange (ETDEWEB)

    Zanova, M. [Oddelenie radiacnej a klinickej onkologie UVN SNP, Ruzomberok (Slovakia)

    2008-07-01

    Colorectal cancer is a worldwide health, social and economic problem. The incidence of malnutrition in patients with colorectal cancer is stated as 54 - 60 %. Primary cachexia is caused by hormonal, metabolic and energetic abnormalities; secondary cachexia is a consequence of functional and anatomic damage to digestive apparatus resulting from a tumor itself or its treatment. Colorectal carcinoma treatment is a complex process involving surgery, radiotherapy and cytostatic treatment. Each treatment modality also brings desirable and undesirable effects and influences patient's nutritional status. Malnutrition worsens patient's overall chances of successful treatment; therefore nutritional support aims to increase his/her anti-infection and antitumor immunity by means of mineral and water industry adjustment as well as by energetic stabilization. (author)

  19. Diet, Gut Microbiota, and Colorectal Cancer Prevention: A Review of Potential Mechanisms and Promising Targets for Future Research.

    Science.gov (United States)

    Song, Mingyang; Chan, Andrew T

    2017-12-01

    Diet plays an important role in the development of colorectal cancer. Emerging data have implicated the gut microbiota in colorectal cancer. Diet is a major determinant for the gut microbial structure and function. Therefore, it has been hypothesized that alterations in gut microbes and their metabolites may contribute to the influence of diet on the development of colorectal cancer. We review several major dietary factors that have been linked to gut microbiota and colorectal cancer, including major dietary patterns, fiber, red meat and sulfur, and obesity. Most of the epidemiologic evidence derives from cross-sectional or short-term, highly controlled feeding studies that are limited in size. Therefore, high-quality large-scale prospective studies with dietary data collected over the life course and comprehensive gut microbial composition and function assessed well prior to neoplastic occurrence are critically needed to identify microbiome-based interventions that ma