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Sample records for sw480 colon carcinoma

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

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    Mirandeli Bautista

    2011-03-01

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

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

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

    2017-04-01

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

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

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

    2016-10-18

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

  4. 5-Geranyloxy-7-methoxycoumarin inhibits colon cancer (SW480) cells growth by inducing apoptosis.

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

    2013-03-01

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

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

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

    2014-09-01

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

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

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    Ai-Qun Liu

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

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

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    Gescher Andreas

    2003-01-01

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

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

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

    2003-01-01

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

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

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

    2016-01-01

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

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

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

    2014-01-01

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

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

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    Park Hae-Duck

    2011-07-01

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

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

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    Akari Takaya

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

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

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

    2016-01-01

    Coxsackievirus A9 (CV-A9) is a pathogenic enterovirus type within the family Picornaviridae. CV-A9 infects A549 human epithelial lung carcinoma cells by attaching to the αVβ6 integrin receptor through a highly conserved Arg-Gly-Asp (RGD) motif, which is located at the exposed carboxy-terminus of the

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

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

    2018-02-01

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

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

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

    2017-10-09

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

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

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    Tomas Nicola M

    2012-07-01

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

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

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

    2008-08-29

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

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

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    Qian Wen-Bin

    2008-08-01

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

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

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

    2011-08-01

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

  20. Vitamin D3 promotes the differentiation of colon carcinoma cells by the induction of E-cadherin and the inhibition of β-catenin signaling

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    Pálmer, Héctor G.; González-Sancho, José Manuel; Espada, Jesús; Berciano, María T.; Puig, Isabel; Baulida, Josep; Quintanilla, Miguel; Cano, Amparo; de Herreros, Antonio García; Lafarga, Miguel; Muñoz, Alberto

    2001-01-01

    The β-catenin signaling pathway is deregulated in nearly all colon cancers. Nonhypercalcemic vitamin D3 (1α,25-dehydroxyvitamin D3) analogues are candidate drugs to treat this neoplasia. We show that these compounds promote the differentiation of human colon carcinoma SW480 cells expressing vitamin D receptors (VDRs) (SW480-ADH) but not that of a malignant subline (SW480-R) or metastasic derivative (SW620) cells lacking VDR. 1α,25(OH)2D3 induced the expression of E-cadherin and other adhesion proteins (occludin, Zonula occludens [ZO]-1, ZO-2, vinculin) and promoted the translocation of β-catenin, plakoglobin, and ZO-1 from the nucleus to the plasma membrane. Ligand-activated VDR competed with T cell transcription factor (TCF)-4 for β-catenin binding. Accordingly, 1α,25(OH)2D3 repressed β-catenin–TCF-4 transcriptional activity. Moreover, VDR activity was enhanced by ectopic β-catenin and reduced by TCF-4. Also, 1α,25(OH)2D3 inhibited expression of β-catenin–TCF-4-responsive genes, c-myc, peroxisome proliferator-activated receptor δ, Tcf-1, and CD44, whereas it induced expression of ZO-1. Our results show that 1α,25(OH)2D3 induces E-cadherin and modulates β-catenin–TCF-4 target genes in a manner opposite to that of β-catenin, promoting the differentiation of colon carcinoma cells. PMID:11470825

  1. The bioactive potential of red raspberry (Rubus idaeus L.) leaves in exhibiting cytotoxic and cytoprotective activity on human laryngeal carcinoma and colon adenocarcinoma.

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    Durgo, Ksenija; Belščak-Cvitanović, Ana; Stančić, Angela; Franekić, Jasna; Komes, Draženka

    2012-03-01

    In this article, the bioactive potential of red raspberry leaves, a by-product of this widely spread plant, mostly valued for its antioxidant-rich fruits, was determined. The polyphenolic profile and antioxidative properties of red raspberry leaf extract were determined and examined for potential biological activity. Cytotoxic effect, antioxidative/prooxidative effect, and effect on total glutathione concentration were determined in human laryngeal carcinoma (HEp2) and colon adenocarcinoma (SW 480) cell lines. SW 480 cells are more susceptible to raspberry leaf extract in comparison with HEp2 cells. The antioxidative nature of raspberry leaf extract was detected in HEp2 cells treated with hydrogen peroxide, as opposed to SW 480 cells, where raspberry leaf extract induced reactive oxygen species formation. Raspberry leaf extract increased total glutathione level in HEp2 cells. This effect was reinforced after 24 hours of recovery, indicating that induction was caused by products formed during cellular metabolism of compounds present in the extract. Comparison of the results obtained on these two cell lines indicates that cellular response to raspberry extract will depend on the type of the cells that are exposed to it. The results obtained confirmed the biological activity of red raspberry leaf polyphenols and showed that this traditional plant can supplement the daily intake of valuable natural antioxidants, which exhibit beneficial health effects.

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

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

    2011-05-20

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

  3. The balance between two isoforms of LEF-1 regulates colon carcinoma growth

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    Wang Shu-Hong

    2012-05-01

    Full Text Available Abstract Background Colon cancer is one of the most aggressive human malignancies, with a very poor prognosis. Although it has been suggested that different isoforms of the lymphoid enhancer factor (LEF-1 have opposing biological activities, the biological outcome of aberrant LEF-1 activation in colon cancer is still unclear. The aim of this study was to evaluate the effect of the different LEF-1 phenotypes on the growth of colon carcinoma cell lines. A deeper understanding of these processes might improve the targeted therapies for colon cancer by regulating the expression of LEF-1. Methods The role of different isoforms of LEF-1 on the growth of human colon carcinoma cell lines (SW480 and HT-29 was studied using various in vitro and in vivo assays. In vitro proliferation, migration, adhesion and apoptosis of the cells stably transfected of different isoforms of LEF-1 were monitored by MTT assay, carboxyfluorescein diacetate–succinimidyl ester staining, annexin V staining, ECM adhesion assay and transwell assay, respectively. In nude mice, the formation of neovasculature in the tumors formed by our constructed cells was measured by immunohistochemistry. All the data were analyzed using a t test, and data were treated as significant when p  Results Overexpression of truncated LEF-1 (LEF-1-ΔL in the colon cell lines, SW480 and HT29, inhibited their growth significantly in vitro and in vivo, but the full-length LEF-1 (LEF-1-FL promoted the proliferation of HT29. Inactivation of Wnt signaling by LEF-1-ΔL reduced the expression of CXCR4 in colon cell lines, which may lead to a decrease in activities such as migration, adhesion and survival. In nude mice, the formation of neovasculature as well as an increase in tumor volume were inhibited by the short isoform of LEF-1. LEF-1-FL, however, caused an increase in all these parameters compared with controls. Conclusions These findings suggest that LEF-1 might play an important role in colon

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

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    Yaqin Wang

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

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

    Science.gov (United States)

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

    2017-04-01

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

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

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

    2009-11-01

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

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

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    Han Yan

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

  8. Rapid eradication of colon carcinoma by Clostridium perfringens Enterotoxin suicidal gene therapy.

    Science.gov (United States)

    Pahle, Jessica; Menzel, Lutz; Niesler, Nicole; Kobelt, Dennis; Aumann, Jutta; Rivera, Maria; Walther, Wolfgang

    2017-02-13

    Bacterial toxins have evolved to an effective therapeutic option for cancer therapy. The Clostridium perfringens enterotoxin (CPE) is a pore-forming toxin with selective cytotoxicity. The transmembrane tight junction proteins claudin-3 and -4 are known high affinity CPE receptors. Their expression is highly upregulated in human cancers, including breast, ovarian and colon carcinoma. CPE binding to claudins triggers membrane pore complex formation, which leads to rapid cell death. Previous studies demonstrated the anti-tumoral effect of treatment with recombinant CPE-protein. Our approach aimed at evaluation of a selective and targeted cancer gene therapy of claudin-3- and/or claudin-4- expressing colon carcinoma in vitro and in vivo by using translation optimized CPE expressing vector. In this study the recombinant CPE and a translation optimized CPE expressing vector (optCPE) was used for targeted gene therapy of claudin-3 and/or -4 overexpressing colon cancer cell lines. All experiments were performed in the human SW480, SW620, HCT116, CaCo-2 and HT-29 colon cancer and the isogenic Sk-Mel5 and Sk-Mel5 Cldn-3-YFP melanoma cell lines. Claudin expression analysis was done at protein and mRNA level, which was confirmed by immunohistochemistry. The CPE induced cytotoxicity was analyzed by the MTT cytotoxicity assay. In addition patient derived colon carcinoma xenografts (PDX) were characterized and used for the intratumoral in vivo gene transfer of the optCPE expressing vector in PDX bearing nude mice. Claudin-3 and -4 overexpressing colon carcinoma lines showed high sensitivity towards both recCPE application and optCPE gene transfer. The positive correlation between CPE cytotoxicity and level of claudin expression was demonstrated. Transfection of optCPE led to targeted, rapid cytotoxic effects such as membrane disruption and necrosis in claudin overexpressing cells. The intratumoral optCPE in vivo gene transfer led to tumor growth inhibition in colon carcinoma PDX

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

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    Thomas Sithara

    2017-09-01

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

  10. Medullary carcinoma of the colon

    DEFF Research Database (Denmark)

    Fiehn, Anne-Marie Kanstrup; Grauslund, Morten; Glenthøj, Anders

    2015-01-01

    Medullary carcinoma of the colon is a rare variant of colorectal cancer claimed to have a more favorable prognosis than conventional adenocarcinomas. The histopathologic appearance may be difficult to distinguish from poorly differentiated adenocarcinoma. The study aimed to evaluate the diagnostic...... interobserver agreement and to characterize the immunohistochemical and molecular differences between these two subgroups. Fifteen cases initially classified as medullary carcinoma and 30 cases of poorly differentiated adenocarcinomas were included. Two pathologists reviewed the slides independently without...... differences in CK20 (p = 0.005) expression and in the rate of BRAF mutations (p = 0.0035). In conclusion, medullary carcinomas of the colon are difficult to discriminate from poorly differentiated adenocarcinoma even with the help of immunohistochemical and molecular analyses. This raises the question whether...

  11. Immunoscintigraphy of colon carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Chatal, J.F.; Saccavini, J.C.; Fumoleau, P.; Douillard, J.Y.; Curtet, C.; Kremer, M.; Le Mevel, B.; Koprowski, H.

    1984-03-01

    Two I-131 labeled monoclonal antibodies that react specifically with human gastrointestinal cancers in cell cultures were administered to 90 cancer patients for the scintigraphic detection of cancer sites. Antibody 17-1A, or its F(ab')/sub 2/ fragments, accumulated significantly in 27 of 46 (59%) colorectal cancer sites, but not in 21 nonepitheliomatous colon cancers and cancers at other sites. Antibody 19-9, or its F(ab')/sub 2/ fragments, showed significant accumulation in 19 out of 29 (66%) colorectal cancer sites. In 17 patients, immunoscintigraphy with antibody 19-9 correlated with an immunoperoxidase study with the same antibody on resected tissue speciments. In 12 patients injected with two antibodies (17-1A + 19-9, or anti-CEA + 19-9), ten of 13 colorectal cancer sites were positive.

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

    Science.gov (United States)

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

    2010-04-01

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

  13. CUB domain containing protein 1 (CDCP1) modulates adhesion and motility in colon cancer cells.

    Science.gov (United States)

    Orchard-Webb, David J; Lee, Thong Chuan; Cook, Graham P; Blair, G Eric

    2014-10-09

    Deregulated expression of the transmembrane glycoprotein CDCP1 (CUB domain-containing protein-1) has been detected in several cancers including colon, lung, gastric, breast, and pancreatic carcinomas. CDCP1 has been proposed to either positively or negatively regulate tumour metastasis. In this study we assessed the role of CDCP1 in properties of cells that are directly relevant to metastasis, namely adhesion and motility. In addition, association between CDCP1 and the tetraspanin protein CD9 was investigated. CDCP1 and CD9 protein expression was measured in a series of colon cancer cell lines by flow cytometry and Western blotting. Adhesion of Colo320 and SW480 cells was determined using a Matrigel adhesion assay. The chemotactic motility of SW480 cells in which CDCP1 expression had been reduced by RNA interference was analysed using the xCELLigence system Real-Time Cell Analyzer Dual Plates combined with 8 μm pore filters. Detergent-resistant membrane fractions were generated following density gradient centrifugation and the CDCP1 and CD9 protein composition of these fractions was determined by Western blotting. The potential association of the CDCP1 and CD9 proteins was assessed by co-immunoprecipitation. Engineered CDCP1 expression in Colo320 cells resulted in a reduction in cell adhesion to Matrigel. Treatment of SW480 cells with CDCP1 siRNA reduced serum-induced chemotaxis. CDCP1 and CD9 cell-surface protein and mRNA levels showed a positive correlation in colon cancer cell lines and the proteins formed a low-level, but detectable complex as judged by co-sedimentation of detergent lysates of HT-29 cells in sucrose gradients as well as by co-immunoprecipitation in SW480 cell lysates. A number of recent studies have assigned a potentially important role for the cell-surface protein CDCP1 in invasion and metastasis of a several types of human cancer cells. In this study, CDCP1 was shown to modulate cell-substratum adhesion and motility in colon cancer cell

  14. Melanocyte colonization and pigmentation of breast carcinoma

    DEFF Research Database (Denmark)

    Mele, Marco; Laurberg, Tinne; Engberg Damsgaard, Tine

    2012-01-01

    Introduction. Melanocyte colonization of breast carcinoma by nonneoplastic melanocytes of epidermal origin is a rare and serious condition first described in 1977. We report on the exceptional clinical and pathological features of this migration phenomenon in a 74-year-old patient. Discussion...

  15. Lymphoepithelioma-Like Carcinoma of the Colon

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    Yasuharu Mori

    2013-03-01

    Full Text Available A 70-year-old female underwent follow-up colonoscopy after colonic polypectomy. The colonoscopy revealed the presence of a 7-mm submucosal tumor in the sigmoid colon. The tumor surface was smooth and covered with normal mucosa. It was diagnosed as a submucosal tumor, and polypectomy was performed. Histopathological examination of the resected specimen revealed moderately to poorly differentiated adenocarcinoma measuring 2 × 5 × 3 mm with marked peritumoral lymphocytic infiltration and lymphoid follicle formation. It was diagnosed as carcinoma with lymphoid stroma (lymphoepithelioma-like carcinoma, SM (1,800 μm, ly2, v0, budding; grade 1. We confirmed the indication for noncurative additional surgical resection and performed laparoscopic sigmoid colectomy. No metastases were observed in the dissected lymph nodes.

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

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    Huiqiang Dou

    2017-11-01

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

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

    Science.gov (United States)

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

    2017-09-01

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

  18. Resveratrol Treatment Inhibits Proliferation of and Induces Apoptosis in Human Colon Cancer Cells.

    Science.gov (United States)

    Feng, Miao; Zhong, Lu-Xing; Zhan, Zheng-Yu; Huang, Zhi-Hao; Xiong, Jian-Ping

    2016-04-04

    Resveratrol, a natural isolate from plant sources, has a long and important history in traditional Chinese medicine. In the present study we investigated the effect of resveratrol on human colon cancer cell lines. We used the Cell Counting kit-8 (CCK-8) for determination of colon cancer cell viability. Apoptosis induction was analyzed using the DeadEnd™ Colorimetric TUNEL System (Promega, Madison, WI, USA). The siRNA Transfection Reagent kit (Santa Cruz Biotechnology, Inc.) was used for the administration of COX-2 silencer RNA (siRNA) into the colon cancer cells. Primer Express® software for Real-Time PCR ver. 3.0 (Applied Biosystems, Foster City, CA, USA) was used to prepare the primers for RT-PCR. The results revealed that exposure of colon cancer cells to resveratrol inhibited cell viability. Resveratrol exhibited a significant inhibitory effect on cell viability at 30 μM concentration after 48 h of exposure. We observed that 30-μM doses of resveratrol for 72 h led to 18, 29, and 34% reduction in the viability of HCA-17, SW480, and HT29 cells, respectively. It also significantly induced apoptosis in both of the tested carcinoma cell lines. The population of apoptotic cells in HCA-17 and SW480 cell lines after 48 h of resveratrol treatment was 59.8±4 and 67.2±4%, respectively, compared to 2.3±1% in the control cells. The colon cancer cells exposed to resveratrol showed significantly lower cyclooxygenase-2 and prostaglandin receptor expression. Treatment of colon cancer cells with the inhibitor of cyclooxygenase-2, indomethacin, and administration of silencer RNA for cyclooxygenase-2 also produced similar results. These findings suggest that resveratrol treatment can be a promising strategy for the treatment of colon cancer.

  19. Colonic neuroendocrine carcinoma in a child

    Energy Technology Data Exchange (ETDEWEB)

    Sasi, Omai Al; Rifai, Ayman; Hugosson, Claes [King Faisal Specialist Hospital and Research Centre, Department of Radiology, MBC 28, Riyadh (Saudi Arabia); Sathiapalan, Rajeev; Kofide, Amani [King Faisal Specialist Hospital and Research Centre, Department of Paediatric Haematology and Oncology, Riyadh (Saudi Arabia); Tulbah, Asthma Mahmoud Mohamed [King Faisal Specialist Hospital and Research Centre, Department of Pathology, Riyadh (Saudi Arabia); Al-Mehaidib, Ali [King Faisal Specialist Hospital and Research Centre, Department of Paediatrics, Riyadh (Saudi Arabia)

    2005-03-01

    A 10-year-old boy with congenital immunodeficiency (X-linked agammaglobulinaemia) presented with loss of appetite and weight, right-sided abdominal pain, diarrhoea and low-grade fever. Radiological investigations with barium follow-through, CT, PET and octreotide scans revealed a primary caecal/ascending proximal colonic mass with liver and bony metastases. Urine screen for 5HIAA was positive. Percutaneous liver biopsy confirmed the diagnosis of neuroendocrine carcinoma. The radiological work-up and the usefulness of various imaging modalities in the diagnosis of this rare paediatric tumour are discussed. The PET scan demonstrated the primary tumour and the metastatic locations more vividly than the octreotide scan, which is currently considered to be the most specific imaging modality for neuroendocrine masses. (orig.)

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

    Science.gov (United States)

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

    2017-01-01

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

  1. Dietary factors and microsatellite instability in sporadic colon carcinomas.

    NARCIS (Netherlands)

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

    2003-01-01

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

  2. Dietary factors and microsatellite instability in sporadic colon carcinomas

    NARCIS (Netherlands)

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

    2003-01-01

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

  3. Reduced expression of TANGO in colon and hepatocellular carcinomas.

    Science.gov (United States)

    Arndt, Stephanie; Bosserhoff, Anja K

    2007-10-01

    The TANGO gene was originally identified as a new family member of the MIA gene family. The gene codes for a 14-kDa protein of so far unknown function. Recently, we identified TANGO as a tumor suppressor in malignant melanoma. In this study we evaluated TANGO transcription in different colon and hepatocellular carcinoma cell lines and tissue samples, to analyze whether loss of TANGO expression is a more general process in tumor development. TANGO was down-regulated or lost in all hepatocellular and colon cell lines compared to primary human hepatocytes or normal colon epithelial cells, respectively, and in most of the tumor samples compared to non-tumorous tissue. These results were confirmed in situ by immunohistochemistry on paraffin-embedded sections of colon and hepatocellular tumors. Functional assays with exogenous TANGO treatment of colon and hepatoma cell lines revealed reduced motility and invasion capacity. Our studies present for the first time the down-regulation of TANGO in colon and hepatocellular carcinoma and provide the first indications for a tumor suppressor role of the TANGO gene in human colon and hepatocellular carcinoma. Thus, functional relevant loss of TANGO expression may contribute to general tumor development and progression, and may provide a new target for therapeutic strategies.

  4. Streptococcus sanguis endocarditis associated with colonic carcinoma.

    Science.gov (United States)

    Nijjer, Sukhjinder; Dubrey, Simon William

    2010-01-01

    Infective endocarditis caused by Streptococcus bovis is known to be associated with colorectal malignancy. Other less common streptococci, specifically Streptococcus sanguis, can be similarly associated with gastrointestinal carcinoma. We present a case of disseminated colorectal carcinoma occurring after a confirmed S sanguis endocarditis, that required mitral valve surgery. There may be a need for gastrointestinal surveillance in patients presenting with bacteraemia caused by less common streptococci.

  5. Clostridium septicum aortitis and colon carcinoma.

    Science.gov (United States)

    Mizrahi, Daniel J; Halpern, Ethan J

    2016-01-01

    Clostridium septicum (C. septicum) aortitis is a rare but highly fatal infection that has a strong association with occult malignancy. Aneurysmal transformation of C. septicum aortitis is common and has been reported to occur in as little as 1 to 3 weeks. We report a case of C. septicum Aortitis with concomitant adenocarcinoma of the ascending colon detected via CT scan. Imaging findings of colonic malignancy with aortitis are highly suggestive of infection with C. septicum. Given the high associated mortality and rapid progression, early recognition on imaging could have life saving implications. Additionally, imaging findings of aortitis in conjunction with C. septicum bacteremia should prompt the careful evaluation for malignancy, most notably colonic or hematologic. Copyright © 2016 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2015-08-01

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

  7. Invasive lobular carcinoma of breast with synchronous colon metastasis

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    Zhu-Jun Loh

    2017-01-01

    Full Text Available Secondary colon malignancy is rare and has a nonspecific presentation. Breast cancer is the second most common malignancy that metastasizes to the gastrointestinal (GI tract. Here, we present the case of a 54-year-old woman diagnosed with breast cancer and synchronous colon metastasis through a positive result obtained from stool occult blood screening. Colonoscopy revealed a subepithelial tumor of the colon. Biopsy revealed metastatic cancer with positive cytokeratin and GATA-binding protein 3 staining, as well as negative caudal-type homeobox 2 staining. A palpable right breast mass with nipple retraction was found, and invasive lobular carcinoma (ILC was diagnosed. Multiple bone, left adrenal gland, para-aortic lymph node, and contralateral breast metastases were detected. Multimodality treatment involving systemic chemotherapy, hormone therapy, and modified radical mastectomy was applied. In our clinical experience, colon metastasis from breast cancer is rare and usually mimics primary colon cancer. High-alert speculation and aggressive biopsy for patients with abnormal GI bleeding are indicated for diagnosis. Patients with colon metastasis from ILC of the breast have a poor prognosis. Therefore, multimodality treatments should be applied to improve their prognosis.

  8. [6]-Gingerol induces caspase-dependent apoptosis and prevents PMA-induced proliferation in colon cancer cells by inhibiting MAPK/AP-1 signaling.

    Science.gov (United States)

    Radhakrishnan, E K; Bava, Smitha V; Narayanan, Sai Shyam; Nath, Lekshmi R; Thulasidasan, Arun Kumar T; Soniya, Eppurathu Vasudevan; Anto, Ruby John

    2014-01-01

    We report mechanism-based evidence for the anticancer and chemopreventive efficacy of [6]-gingerol, the major active principle of the medicinal plant, Ginger (Zingiber officinale), in colon cancer cells. The compound was evaluated in two human colon cancer cell lines for its cytotoxic effect and the most sensitive cell line, SW-480, was selected for the mechanistic evaluation of its anticancer and chemopreventive efficacy. The non-toxic nature of [6]-gingerol was confirmed by viability assays on rapidly dividing normal mouse colon cells. [6]-gingerol inhibited cell proliferation and induced apoptosis as evidenced by externalization of phosphatidyl serine in SW-480, while the normal colon cells were unaffected. Sensitivity to [6]-gingerol in SW-480 cells was associated with activation of caspases 8, 9, 3 &7 and cleavage of PARP, which attests induction of apoptotic cell death. Mechanistically, [6]-gingerol down-regulated Phorbol Myristate Acetate (PMA) induced phosphorylation of ERK1/2 and JNK MAP kinases and activation of AP-1 transcription factor, but had only little effects on phosphorylation of p38 MAP kinase and activation of NF-kappa B. Additionally, it complemented the inhibitors of either ERK1/2 or JNK MAP kinase in bringing down the PMA-induced cell proliferation in SW-480 cells. We report the inhibition of ERK1/2/JNK/AP-1 pathway as a possible mechanism behind the anticancer as well as chemopreventive efficacy of [6]-gingerol against colon cancer.

  9. [6]-Gingerol induces caspase-dependent apoptosis and prevents PMA-induced proliferation in colon cancer cells by inhibiting MAPK/AP-1 signaling.

    Directory of Open Access Journals (Sweden)

    E K Radhakrishnan

    Full Text Available We report mechanism-based evidence for the anticancer and chemopreventive efficacy of [6]-gingerol, the major active principle of the medicinal plant, Ginger (Zingiber officinale, in colon cancer cells. The compound was evaluated in two human colon cancer cell lines for its cytotoxic effect and the most sensitive cell line, SW-480, was selected for the mechanistic evaluation of its anticancer and chemopreventive efficacy. The non-toxic nature of [6]-gingerol was confirmed by viability assays on rapidly dividing normal mouse colon cells. [6]-gingerol inhibited cell proliferation and induced apoptosis as evidenced by externalization of phosphatidyl serine in SW-480, while the normal colon cells were unaffected. Sensitivity to [6]-gingerol in SW-480 cells was associated with activation of caspases 8, 9, 3 &7 and cleavage of PARP, which attests induction of apoptotic cell death. Mechanistically, [6]-gingerol down-regulated Phorbol Myristate Acetate (PMA induced phosphorylation of ERK1/2 and JNK MAP kinases and activation of AP-1 transcription factor, but had only little effects on phosphorylation of p38 MAP kinase and activation of NF-kappa B. Additionally, it complemented the inhibitors of either ERK1/2 or JNK MAP kinase in bringing down the PMA-induced cell proliferation in SW-480 cells. We report the inhibition of ERK1/2/JNK/AP-1 pathway as a possible mechanism behind the anticancer as well as chemopreventive efficacy of [6]-gingerol against colon cancer.

  10. A CASE REPORT OF MULTIPLE PRIMARY SQUAMOUS CELL CARCINOMAS OF THE OVARY AND SIGMOID COLON

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    A. B. Villert

    2016-01-01

    Full Text Available Squamous cell ovarian and sigmoid colon carcinomas are extremely rare malignancies. Because of their rarity, it is difficult to investigate the clinical characteristics and prognosis of patients with theses malignancies, and therefore, the increased interest in each clinical case report is highly relevant. Multiple primary squamous cell ovarian and sigmoid colon carcinomas are the subject of discussion and differential diagnosis of sigmoid colon cancer with secondary ovarian cancer. Histopathological and clinical characteristics of the tumors were present and evidences in favor of the multiple primary malignancies were given. The association of squamous cell ovarian and sigmoid colon carcinomas with human papilloma virus type 16 was shown.

  11. Synchronous Carcinoma of the Ampulla of Vater and Colon Cancer

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    Anastasios J. Karayiannakis

    2011-05-01

    Full Text Available Carcinoma of the papilla of Vater is a relatively rare tumor and its coexistence with other primary sporadic cancers is very exceptional. Here we report the case of a 76-year-old man who presented with painless obstructive jaundice, pathologically elevated liver function tests and increased serum levels of carbohydrate antigen 19-9 and carcinoembryonic antigen. Endoscopic retrograde cholangiography revealed a large polypoid mass in the ampulla of Vater. A large tumor in the ascending colon was also incidentally detected by abdominal computed tomography. Endoscopic biopsies from both lesions showed adenocarcinomas. Metastases to the liver and to the hepatoduodenal ligament and hepatic artery lymph nodes were found during surgery. Right colectomy and a biliary bypass were performed. Histological analysis showed an ampullary adenocarcinoma with metastases to regional lymph nodes and the liver and a colonic adenocarcinoma with local invasion into the pericolic fat. Treatment with gemcitabine plus cisplatin was suggested postoperatively. The association of sporadic ampullary and colonic adenocarcinomas and the mutually increased risk of developing either a synchronous or a metachronous tumor following each other should be considered in patients with primary ampullary or colorectal cancer during the preoperative evaluation and postoperative follow-up of these patients.

  12. Endometriosis presenting as carcinoma colon in a perimenopausal woman

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    Tanuja Muthyala

    2015-01-01

    Full Text Available Endometriosis is a common benign disease of reproductive age women, and can involve the intestinal tract. Inconsistent clinical presentation, similar features on radiological imaging and colonoscopy with other inflammatory and malignant lesions of the bowel makes the preoperative diagnosis of bowel endometriosis difficult. We present a case of a 42-year-old perimenopausal female clinically presented, investigated and managed in the lines of carcinoma of sigmoid colon. She underwent terminal ileac resection with end to end anastomoses, Hartmann′s procedure and total hysterectomy with bilateral salpingoophorectomy. The histopathological report revealed endometriosis of small intestine, large intestine, mesentery, right ovary and adenomyoma of uterus. Thus, bowel endometriosis should also be considered as differential diagnosis in reproductive age women with gastrointestinal symptoms or intestinal mass of uncertain diagnosis.

  13. Synchronous Occurrence of Primary Breast Carcinoma and Primary Colon Adenocarcinoma.

    Science.gov (United States)

    Yetkin, Gurkan; Celayir, Fevzi; Akgun, Ismail Ethem; Ucak, Ramazan

    2017-01-01

    A 65-year-old female patient presented to the emergency clinic with abdominal pain, meteorism, and intermittent rectal bleeding. Colonoscopy was performed, and a hepatic flexure tumor was detected. Histopathological examination of biopsy revealed adenocarcinoma. Thoracoabdominal CT was performed for staging, and a spiculated contour mass was found incidentally on the left breast. Mammography and ultrasonography were performed for the cause of these findings, and suspicious lesions of malignancy were seen in the left breast. Invasive ductal carcinoma was detected in core needle biopsy samples from lesions. In the multidisciplinary council consisting of oncologist, pathologist, radiologist, and general surgery specialist, it was decided to perform breast operation first and then colon operation, followed by adjuvant chemotherapy. In the first operation, left total mastectomy and sentinel lymph node biopsy were performed. One week after her initial operation, the patient underwent right hemicolectomy. After operations, the patient did not develop postoperative complications and was sent to medical oncology department for adjuvant chemotherapy.

  14. Metastasis of colon cancer to medullary thyroid carcinoma: a case report.

    Science.gov (United States)

    Yeo, So-Jung; Kim, Kyu-Jin; Kim, Bo-Yeon; Jung, Chan-Hee; Lee, Seung-Won; Kwak, Jeong-Ja; Kim, Chul-Hee; Kang, Sung-Koo; Mok, Ji-Oh

    2014-10-01

    Metastasis to the primary thyroid carcinoma is extremely rare. We report here a case of colonic adenocarcinoma metastasis to medullary thyroid carcinoma in a 53-yr old man with a history of colon cancer. He showed a nodular lesion, suggesting malignancy in the thyroid gland, in a follow-up examination after colon cancer surgery. Fine needle aspiration biopsy (FNAB) of the thyroid gland showed tumor cell clusters, which was suspected to be medullary thyroid carcinoma (MTC). The patient underwent a total thyroidectomy. Using several specific immunohistochemical stains, the patient was diagnosed with colonic adenocarcinoma metastasis to MTC. To the best of our knowledge, the present patient is the first case of colonic adenocarcinoma metastasizing to MTC. Although tumor-tumor metastasis to primary thyroid carcinoma is very rare, we still should consider metastasis to the thyroid gland, when a patient with a history of other malignancy presents with a new thyroid finding.

  15. Microsatellite instability in medullary carcinoma of the colon

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    Mario Martinotti

    2017-03-01

    Full Text Available Medullary carcinoma (MC of the large intestine is a relatively new histological type of adenocarcinoma characterized by poor glandular differentiation and an intraepithelial lymphocytic infiltrate. MC can be associated to a defective mechanism for DNA mismatch repair, caused by the so-called microsatellite instability (MSI. We present the case of a 44 years old Caucasian woman, who referred to the Emergency Room with symptoms mimicking an acute appendicitis. Computed tomography and colonoscopy demonstrated an ulcerated and stenotic lesion of the caecum without signs of metastasis and peritoneal carcinosis. Patient underwent a laparoscopic right colectomy. The final pathologic findings provided the diagnosis of medullary carcinoma with MSI. Patient then underwent adjuvant chemotherapy according to the FOLFOX- 4 protocol (association of 5-Fluorouracil, Leucovorin, and Oxaliplatin for twelve cycles. At two-years follow-up, patient is disease free. MC in association with MSI is a non-frequent tumor of the colon characterized by a better prognosis compared to other types of poorly differentiated adenocarcinoma. In the observed case, 24 months after the surgical operation, the patient is in good health and there is no evidence of metastasis or relapse.

  16. MiR-9, -31, and -182 deregulation promote proliferation and tumor cell survival in colon cancer.

    Science.gov (United States)

    Cekaite, Lina; Rantala, Juha K; Bruun, Jarle; Guriby, Marianne; Agesen, Trude H; Danielsen, Stine A; Lind, Guro E; Nesbakken, Arild; Kallioniemi, Olli; Lothe, Ragnhild A; Skotheim, Rolf I

    2012-09-01

    Several microRNAs (miRNAs) are known to be deregulated in colon cancer, but the mechanisms behind their potential involvement on proliferation and tumor cell survival are unclear. The present study aimed to identify miRNAs with functional implications for development of colon cancer. The cell proliferation and apoptosis were examined following perturbations of miRNA levels by employing a comprehensive miRNA library screen. miRNAs nominated for relevance to colon cancer were validated on expression and functional levels. By integrating the effect of miRNA up-regulation with the endogenous miRNA expression levels within the HT29, HCT116, and SW480 colon cancer cell lines, we identified miRNAs controlling cell proliferation (n = 53) and apoptosis (n = 93). From these functionally nominated miRNAs, we narrowed the list to 10 oncogene- and 20 tumor suppressor-like miRNAs that were also differentially expressed between colon cancer (n = 80) and normal colonic mucosa (n = 20). The differential expressions of miR-9, miR-31, and miR-182 were successfully validated in a series of colon carcinomas (n = 30) and polyps (n = 10) versus normal colonic mucosa (n = 10), whereas the functional effect was confirmed in an in-depth validation using different cell viability and apoptotic markers. Several transcription factors and genes regulating cell proliferation were identified as putative target genes by integrative miRNA/mRNA expression analysis obtained from the same colon cancer patient samples. This study suggests that deregulated expression of miR-9, miR-31, and miR-182 during carcinogenesis plays a significant role in the development of colon cancer by promoting proliferation and tumor cell survival.

  17. MiR-9, -31, and -182 Deregulation Promote Proliferation and Tumor Cell Survival in Colon Cancer12

    Science.gov (United States)

    Cekaite, Lina; Rantala, Juha K; Bruun, Jarle; Guriby, Marianne; Ågesen, Trude H; Danielsen, Stine A; Lind, Guro E; Nesbakken, Arild; Kallioniemi, Olli; Lothe, Ragnhild A; Skotheim, Rolf I

    2012-01-01

    Several microRNAs (miRNAs) are known to be deregulated in colon cancer, but the mechanisms behind their potential involvement on proliferation and tumor cell survival are unclear. The present study aimed to identify miRNAs with functional implications for development of colon cancer. The cell proliferation and apoptosis were examined following perturbations of miRNA levels by employing a comprehensive miRNA library screen. miRNAs nominated for relevance to colon cancer were validated on expression and functional levels. By integrating the effect of miRNA up-regulation with the endogenous miRNA expression levels within the HT29, HCT116, and SW480 colon cancer cell lines, we identified miRNAs controlling cell proliferation (n = 53) and apoptosis (n = 93). From these functionally nominated miRNAs, we narrowed the list to 10 oncogene- and 20 tumor suppressor-like miRNAs that were also differentially expressed between colon cancer (n = 80) and normal colonic mucosa (n = 20). The differential expressions of miR-9, miR-31, and miR-182 were successfully validated in a series of colon carcinomas (n = 30) and polyps (n = 10) versus normal colonic mucosa (n = 10), whereas the functional effect was confirmed in an in-depth validation using different cell viability and apoptotic markers. Several transcription factors and genes regulating cell proliferation were identified as putative target genes by integrative miRNA/mRNA expression analysis obtained from the same colon cancer patient samples. This study suggests that deregulated expression of miR-9, miR-31, and miR-182 during carcinogenesis plays a significant role in the development of colon cancer by promoting proliferation and tumor cell survival. PMID:23019418

  18. MiR-9, -31, and -182 Deregulation Promote Proliferation and Tumor Cell Survival in Colon Cancer

    Directory of Open Access Journals (Sweden)

    Lina Cekaite

    2012-09-01

    Full Text Available Several microRNAs (miRNAs are known to be deregulated in colon cancer, but the mechanisms behind their potential involvement on proliferation and tumor cell survival are unclear. The present study aimed to identify miRNAs with functional implications for development of colon cancer. The cell proliferation and apoptosis were examined following perturbations of miRNA levels by employing a comprehensive miRNA library screen. miRNAs nominated for relevance to colon cancer were validated on expression and functional levels. By integrating the effect of miRNA up-regulation with the endogenous miRNA expression levels within the HT29, HCT116, and SW480 colon cancer cell lines, we identified miRNAs controlling cell proliferation (n = 53 and apoptosis (n = 93. From these functionally nominated miRNAs, we narrowed the list to 10 oncogene- and 20 tumor suppressor-like miRNAs that were also differentially expressed between colon cancer (n = 80 and normal colonic mucosa (n = 20. The differential expressions of miR-9, miR-31, and miR-182 were successfully validated in a series of colon carcinomas (n = 30 and polyps (n = 10 versus normal colonic mucosa (n = 10, whereas the functional effect was confirmed in an in-depth validation using different cell viability and apoptotic markers. Several transcription factors and genes regulating cell proliferation were identified as putative target genes by integrative miRNA/mRNA expression analysis obtained from the same colon cancer patient samples. This study suggests that deregulated expression of miR-9, miR-31, and miR-182 during carcinogenesis plays a significant role in the development of colon cancer by promoting proliferation and tumor cell survival.

  19. Colon cancer

    Science.gov (United States)

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

  20. Griffonia simplicifolia agglutinin-2-binding glycoprotein as a novel carbohydrate antigen of human colonic carcinoma.

    Science.gov (United States)

    Nakayama, J; Okano, A; Maeda, H; Miyachi, M; Ota, H; Katsuyama, T; Kanai, M

    1990-04-01

    Griffonia simplicifolia agglutinin-2-binding glycoprotein (GBG) in human colonic carcinoma was examined immunochemically and histochemically, GBG was extracted from colonic carcinoma as a serum-type glycoprotein of 160 kilodaltons. GBG was not identical with carcinoembryonic antigen (CEA), since its molecular weight and localization in tissue sections were different from those of CEA. The non-reducing terminals of GBG probably carry N-acetylglucosamine, but not blood group determinants. Furthermore, GBG was released by phosphatidylinositol-specific phospholipase C from cell membrane. GBG was suggested to be anchored to the membrane via linkage to a glycosyl-phosphatidylinositol molecule. Among colonic carcinoma-associated antigens, serum-type glycoproteins having N-acetylglucosamine at non-reducing terminals have not previously been reported. GBG is a novel carbohydrate antigen of human colonic carcinoma.

  1. Synchronous Occurrence of Primary Breast Carcinoma and Primary Colon Adenocarcinoma

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    Gurkan Yetkin

    2017-01-01

    Full Text Available A 65-year-old female patient presented to the emergency clinic with abdominal pain, meteorism, and intermittent rectal bleeding. Colonoscopy was performed, and a hepatic flexure tumor was detected. Histopathological examination of biopsy revealed adenocarcinoma. Thoracoabdominal CT was performed for staging, and a spiculated contour mass was found incidentally on the left breast. Mammography and ultrasonography were performed for the cause of these findings, and suspicious lesions of malignancy were seen in the left breast. Invasive ductal carcinoma was detected in core needle biopsy samples from lesions. In the multidisciplinary council consisting of oncologist, pathologist, radiologist, and general surgery specialist, it was decided to perform breast operation first and then colon operation, followed by adjuvant chemotherapy. In the first operation, left total mastectomy and sentinel lymph node biopsy were performed. One week after her initial operation, the patient underwent right hemicolectomy. After operations, the patient did not develop postoperative complications and was sent to medical oncology department for adjuvant chemotherapy.

  2. Ameboma: A Colon Carcinoma-Like Lesion in a Colonoscopy Finding

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    Chung-Cheng Lin

    2013-10-01

    Full Text Available Ameboma is a rare complication of amebic colitis presenting as a mass of granulation tissue with peripheral fibrosis and a core of inflammation related to amebic chronic infection. The initial presentations are usually obstruction and low gastrointestinal bleeding. The most common sites are the ascending colon and the cecum. It may mimic colon carcinoma, Crohn's disease, carcinoma of the colon, non-Hodgkin's lymphoma, tuberculosis, fungal infection, AIDS-associated lymphoma and Kaposi's sarcoma in colonoscopy findings. The therapeutic strategy should be combined with antibiotics for invasive dysentery and eradication of luminal cysts.

  3. Chromophobe Renal Cell Carcinoma and the Synchronous Presence of Primary Colon Malignancies. Is There a Relation?

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    Georgios Sahsamanis

    2017-09-01

    Full Text Available While the presence of multiple primary malignancies in the same patient is a well described phenomenon, there is no clear association between various histological subtypes of renal cell carcinoma (RCC and the synchronous presence of colon malignancies. We present the rare case of an 81-year-old female patient suffering from chromophobe renal cell carcinoma (chRCC and an angiomyolipoma of her left kidney, synchronous with an adenocarcinoma of the caecum. While there is an established connection between RCC and colon cancer, a literature review is performed to specify this association in regard to chRCC and the synchronous presence of colon malignancies.

  4. The retroperitoneal surface in distal caecal and proximal ascending colon carcinoma: the Cinderella surgical margin?

    Science.gov (United States)

    Bateman, A C; Carr, N J; Warren, B F

    2005-01-01

    Background: Mesorectal margin tumour involvement is a predictor of local recurrence in rectal carcinoma and an indication for postoperative radiotherapy in suitable patients. However, the prevalence of non-peritonealised surgical margin involvement in ascending colon carcinoma is unknown. Aims: To test the hypothesis that retroperitoneal surgical margin (RSM) tumour involvement occurs in distal caecal and proximal ascending colon carcinoma. Methods/Results: One hundred right hemicolectomy specimens, removed for adenocarcinoma of the caecum or proximal ascending colon, were studied. During routine specimen dissection, at least one additional tissue block was taken to include the tumour and the RSM. The tumour distance from the RSM was recorded. RSM tumour involvement was present in seven cases (7%). Direct (non-nodal) RSM tumour involvement (five cases) only occurred in posterior or circumferential tumours. Conclusions: RSM tumour involvement occurs within a considerable number of distal caecal and proximal ascending colon carcinomas. The rate of RSM tumour involvement identified here is similar to a previously published local recurrence rate of 10% in caecal carcinoma, suggesting that RSM tumour involvement may be a predictor of recurrence in these tumours. Therefore, patients with distal caecal or proximal ascending colon carcinoma and RSM tumour involvement may benefit from postoperative radiotherapy. PMID:15790712

  5. Induction of retinoic acid receptor β mediates growth inhibition in retinoid resistant human colon carcinoma cells

    OpenAIRE

    Nicke, B; Riecken, E; Rosewicz, S

    1999-01-01

    BACKGROUND—The molecular mechanisms underlying the differential sensitivity of human colon carcinoma cells to retinoid mediated growth inhibition are poorly understood.
AIM—To identify the intracellular mechanisms responsible for resistance against retinoid mediated growth inhibition in human colon carcinoma cells.
METHODS—Anchorage independent growth of the human colon carcinoma cell lines HT29 and LoVo was determined by a human tumour clonogenic assay. Retinoid receptor expression was evalu...

  6. Adenosquamous carcinoma of the colon, rectum, and anus: epidemiology, distribution, and survival characteristics.

    Science.gov (United States)

    Cagir, B; Nagy, M W; Topham, A; Rakinic, J; Fry, R D

    1999-02-01

    There have been 49 cases of adenosquamous carcinoma of the colon, rectum, and anus reported in the English literature. We have reviewed 145 cases of adenosquamous carcinoma to better define epidemiologic and survival characteristics of this extremely rare colon carcinoma. The National Cancer Institute's Surveillance, Epidemiology, and End Results program public use CD-ROM file for the years 1973 through 1992 were reviewed. This represents approximately 9.5 percent of the United States population. Adenosquamous carcinomas arising in the colon, rectum, and anus were identified using the International Classification of Diseases-O codes. The Astler-Coller tumor classification was used for staging. Two-tailed Student's t-test, Mantel-Haenszel chi-squared tests, and generalized Wilcoxon's tests were used for comparisons of means, proportions, and actuarial survival rates, respectively. Survival curves were calculated by the Kaplan-Meier method. One hundred forty-five cases of adenosquamous carcinoma were identified, representing 0.06 percent of all colorectal malignancies. The mean age of patients was 67 years. Eighty-four percent of patients were Caucasians, 15 percent were Afro-Americans, and 1 percent were other races. Afro-Americans were diagnosed at a significantly younger age (median age, 62 years; P = 0.03). Fifty-three percent of the carcinomas were located in the sigmoid colon, rectum, and anus, 28 percent in the right colon, and the rest in the middle segment. Seventy-four percent of distal cases were staged A through C, compared with 44 percent of proximal cases. Patients with adenosquamous carcinoma of the sigmoid colon, rectum, and anus survived longer than all other patients (P = 0.001). Patients with adenosquamous carcinoma Stages A and B1 had survival rates similar to patients with comparably staged adenocarcinomas. Fifty percent of the patients, including most of the patients with D stage, died in the first year. Patients with Stages B2, C, and D

  7. Single Nucleotide Polymorphism (rs4932178 in the P1 Promoter of FURIN Is Not Prognostic to Colon Cancer

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    Jeroen Declercq

    2015-01-01

    Full Text Available High expression of the proprotein processing enzyme FURIN has been associated with tumor progression and metastasis. A SNP (rs4932178 in the promoter of FURIN has been reported to affect expression in liver, with the T allele resulting in higher expression than the C allele. In this study we have investigated the association of this SNP with prognostic and biological subgroups of colorectal cancer (CRC. In a panel of 1382 patients with CRC, this SNP had no impact on overall survival or on postoperative risk of relapse. This SNP also could not be linked with FURIN expression levels in CRC samples from the patients. Furthermore, we demonstrate in luciferase reporter experiments in the colon cancer cell lines Caco-2 and SW480 and in the hepatocellular carcinoma cell line Huh\t7 that expression is not affected by the SNP. Since, FURIN inhibition in human colon cancer cell lines has previously been shown to repress tumor metastases, association between FURIN gene expression levels and postoperative relapse-free survival was also investigated. However, no association could be found. Altogether, we could not confirm an effect of the SNP on FURIN expression in vitro and no correlations could be found in vivo with FURIN expression or outcome.

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

    Science.gov (United States)

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

    2017-07-01

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

  9. Successful one stage operation for a synchronous, duodenal carcinoma, colonic carcinoma and renal oncocytoma in an adult patient.

    Science.gov (United States)

    Faraj, Walid; Sbaity, Eman; Mukherji, Deborah; Shamseddine, Ashraf; Shamseddine, Ali; Khalife, Mohamed

    2011-09-01

    We report a rare case of synchronous duodenal carcinoma, colonic carcinoma and renal oncocytoma successfully treated using a one-stage surgical approach. Potential risk factors for multiple primary malignancies associated with duodenal carcinoma are discussed. This case illustrates several practice points for consideration: 1. Patients presenting with small intestinal carcinomas have a higher than average chance of developing second primary tumors in other organs; this should be taken into consideration during staging and follow-up. 2. For full staging of patients presenting with small bowel tumors, upper and lower gastrointestinal endoscopy and PET scanning should be considered. 3. A one-stage surgical procedure can be used safely and successfully for multiple synchronous primary tumors.

  10. Successful one stage operation for a synchronous, duodenal carcinoma, colonic carcinoma and renal oncocytoma in an adult patient

    Directory of Open Access Journals (Sweden)

    Shamseddine Ali

    2011-09-01

    Full Text Available Abstract We report a rare case of synchronous duodenal carcinoma, colonic carcinoma and renal oncocytoma successfully treated using a one-stage surgical approach. Potential risk factors for multiple primary malignancies associated with duodenal carcinoma are discussed. This case illustrates several practice points for consideration: 1. Patients presenting with small intestinal carcinomas have a higher than average chance of developing second primary tumors in other organs; this should be taken into consideration during staging and follow-up. 2. For full staging of patients presenting with small bowel tumors, upper and lower gastrointestinal endoscopy and PET scanning should be considered. 3. A one-stage surgical procedure can be used safely and successfully for multiple synchronous primary tumors.

  11. Successful one stage operation for a synchronous, duodenal carcinoma, colonic carcinoma and renal oncocytoma in an adult patient

    Science.gov (United States)

    2011-01-01

    We report a rare case of synchronous duodenal carcinoma, colonic carcinoma and renal oncocytoma successfully treated using a one-stage surgical approach. Potential risk factors for multiple primary malignancies associated with duodenal carcinoma are discussed. This case illustrates several practice points for consideration: 1. Patients presenting with small intestinal carcinomas have a higher than average chance of developing second primary tumors in other organs; this should be taken into consideration during staging and follow-up. 2. For full staging of patients presenting with small bowel tumors, upper and lower gastrointestinal endoscopy and PET scanning should be considered. 3. A one-stage surgical procedure can be used safely and successfully for multiple synchronous primary tumors. PMID:21884600

  12. Experiment list: SRX398302 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available =SW480 || cell type=Colon Carcinoma http://dbarchive.biosciencedbc.jp/kyushu-u/hg...|Tissue Diagnosis=unresolved 48784023,96.4,55.9,5475 GSM1296645: SW480 CDK8 ChipSeq; Homo sapiens; ChIP-Seq source_name=Colon Carcino...ma || chip antibody=CDK8 || antibody catalog number=Santa Cruz SC-1521 || cell line

  13. Hepatic tuberculosis mimicking metastasis in a case of carcinoma sigmoid colon

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    Musharraf Husain

    2015-01-01

    Full Text Available Tuberculosis (TB presenting as isolated liver mass without clinical evidence of TB is difficult to diagnose preoperatively and is usually mimicked by primary or metastatic carcinoma of the liver. Hepatic TB associated with carcinoma colon is a rare association which has very rarely been reported in the literature. This case illustrates the diagnostic difficulties of hepatic TB and the need to consider it in the differential diagnosis of hepatic nodular lesions in carcinoma colon patients. Here, we report a case of 48-year-old female who presented in the casualty with features of acute intestinal obstruction. Preoperatively a mass was seen at the hepatic flexure along with three lesions in the liver presumed to be metastatic in origin. However, histopathology of the mass revealed adenocarcinoma colon and the liver lesion proved to be hepatic TB. We wish to highlight that on encountering a hepatic lesion in a carcinoma colon patient the possibility of hepatic TB should also be kept in mind apart from the obvious possibility of metastasis especially in an endemic country like India.

  14. Synchronous colonic carcinomas presenting as an inguinoscrotal hernial mass: a case report.

    Science.gov (United States)

    Tan, Siao Pei; Liau, Siong-Seng; Habeeb, Shayma'u M; O'riordan, Dermot

    2007-06-28

    A carcinoma within a hernia in the groin is uncommon, with an incidence of less than 0.5 percent of all excised sacs. This article describes a case of synchronous colonic carcinomas, one of which presented as an inguinoscrotal mass. A 69-year old man presented with a large, irreducible left inguinoscrotal hernia and symptoms of obstruction. On examination, there was an 8 cm palpable mass within the hernia sac. CT scan revealed small and proximal large bowel obstruction secondary to a large ingunoscrotal sac and synchronous colonic tumours of the transverse colon and the ascending colon. The former presented as an inguinoscrotal mass. Laparotomy revealed a large tumour mass arising from the transverse colon in the hernia sac. The procedure was followed by an extended right hemicolectomy, during which the second tumour in the ascending colon was also resected. This case demonstrates a rare but interesting occurrence of primary transverse colon carcinoma presenting in a hernia sac, in conjunction with a synchronous tumour of the ascending colon. Prognosis is comparable to patients with a solitary tumour of similar pathological staging when the resection is curative. The presence of an inguinal hernia itself does not signify an increased risk of colorectal malignancy. However, in the presence of obstruction, incarceration, and weight loss, malignancy should be suspected. Thorough clinical examination, flexible sigmoidoscopy or radiographic evaluation is necessary preoperatively in such patients. Surgical resection, with or without adjuvant oncological treatment, should be performed as soon as possible, using established techniques with modifications according to involvement of local structures.

  15. Synchronous colonic carcinomas presenting as an inguinoscrotal hernial mass: a case report

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    Tan Siao

    2007-06-01

    Full Text Available Abstract Background A carcinoma within a hernia in the groin is uncommon, with an incidence of less than 0.5 percent of all excised sacs. This article describes a case of synchronous colonic carcinomas, one of which presented as an inguinoscrotal mass. Case presentation A 69-year old man presented with a large, irreducible left inguinoscrotal hernia and symptoms of obstruction. On examination, there was an 8 cm palpable mass within the hernia sac. CT scan revealed small and proximal large bowel obstruction secondary to a large ingunoscrotal sac and synchronous colonic tumours of the transverse colon and the ascending colon. The former presented as an inguinoscrotal mass. Laparotomy revealed a large tumour mass arising from the transverse colon in the hernia sac. The procedure was followed by an extended right hemicolectomy, during which the second tumour in the ascending colon was also resected. Conclusion This case demonstrates a rare but interesting occurrence of primary transverse colon carcinoma presenting in a hernia sac, in conjunction with a synchronous tumour of the ascending colon. Prognosis is comparable to patients with a solitary tumour of similar pathological staging when the resection is curative. The presence of an inguinal hernia itself does not signify an increased risk of colorectal malignancy. However, in the presence of obstruction, incarceration, and weight loss, malignancy should be suspected. Thorough clinical examination, flexible sigmoidoscopy or radiographic evaluation is necessary preoperatively in such patients. Surgical resection, with or without adjuvant oncological treatment, should be performed as soon as possible, using established techniques with modifications according to involvement of local structures.

  16. Polyyne-Enriched Extract from Oplopanax elatus Significantly Ameliorates the Progression of Colon Carcinogenesis in ApcMin/+ Mice

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    Xin Qiao

    2017-09-01

    Full Text Available Colorectal cancer (CRC is the third most common cancer in the world. Oplopanax elatus is widely used in traditional medicine. However, little is known about its pharmacological effects and bioactive compounds. We evaluated the effects of the polyyne-enriched extract from O. elatus (PEO on the progression of colon carcinogenesis in ApcMin/+ mice. In addition, these effects were also investigated in HCT116 and SW480 cells. After PEO oral administration (0.2% diet for 12 weeks, PEO significantly improved body weight changes and reduced the tumor burden and tumor multiplicity compared with the untreated mice. Meanwhile, western blot and immunohistochemistry results showed PEO significantly reduced the expression of β-catenin and cyclinD1 in both small intestine and the colon tissues compared with the untreated mice. In addition, PEO treatment significant decreased the cell viability in both HCT116 and SW480 cell lines. It also decreased the levels of β-catenin, cyclinD1, c-myc and p-GSK-3β in HCT116 and SW480 cells at 25 μM. These results indicate that PEO may have potential value in prevention of colon cancer by down-regulating Wnt-related protein.

  17. Double contrast examination in carcinoma of the colon and rectum. A prospective clinical series

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    Fork, F.T.; Lindstroem, C.; Ekelund, G. (Malmoe Allmaenna Sjukhus (Sweden). Dept. of Diagnostic Radiology)

    1983-01-01

    During a 9-month period, 2,590 patients were referred for radiographic examination of the large bowel. All but 55 of these examinations were performed according to the double contrast examination method. The patients were followed prospectively from 40 to 48 months. Carcinoma of the colon or rectum was disclosed in 96 patients and other malignant lesions in 7 others. The carcinomas in 93 patients were diagnosed at the primary DCE. During the follow-up period, carcinoma of the colon was revealed in another 10 patients, the malignancy having been obfuscated by diverticulitis in 3 patients and considered polyps in 6 others. The accuracy of the double contrast method was calculated at 99.3 per cent.

  18. [A Case of Undifferentiated Carcinoma of the Sigmoid Colon That Responded to Paclitaxel and Carboplatin Chemotherapy].

    Science.gov (United States)

    Toyama, Shingo; Kudoh, Katsuyoshi; Ohnuma, Shinobu; Sato, Satoko; Tanaka, Naoki; Aoki, Takeshi; Imoto, Hirofumi; Karasawa, Hideaki; Watanabe, Kazuhiro; Nagao, Munenori; Abe, Tomoya; Musha, Hiroaki; Motoi, Fuyuhiko; Naitoh, Takeshi; Unno, Michiaki

    2016-11-01

    We report a case of a 72-year-old woman who was initially diagnosed with ovarian cancer with peritoneal carcinomatosis. Systemic chemotherapy consisting of paclitaxel and carboplatin(TC)was administered. Although a partial response(PR)was achieved after the 4 courses of TC, this regimen was discontinued due to severe adverse events. Ten months after discontinuation of TC, because abdominal CT and colonoscopy showed an intra-tumoral abscess caused by invasion of the tumor to the sigmoid colon, abdominal total hysterectomy, bilateral salpingo-oophorectomy, and a Hartmann's operation were performed to control the disease symptoms. Pathological examination revealed that the tumor was an undifferentiated carcinoma of the sigmoid colon. This case report suggests that the TC regimen may be effective for treating undifferentiated carcinoma of the colon.

  19. A case of descending colon carcinoma metastasized to left spermatic cord, testis, and epididymis

    Science.gov (United States)

    Augustin, Herbert; Popper, Helmut; Pummer, Karl

    2012-01-01

    We report a case of descending colon carcinoma metastasized to the left spermatic cord, testis, and epididymis. A 77-year old male patient underwent a left hemicolectomy for a descending colon cancer. He was referred to our department because of swelling and pain of the left scrotum two years and six months after surgery. High left orchiectomy was performed. Histological examination revealed a metastasis of the colon carcinoma within the spermatic cord and epididymis approaching the testicle. Reports on metastatic cancer of the testis are scarce, because this metastatic cancer is extremely rare. In general, testicular pain is rare in the elderly. We suggest that any elder presenting with testicular pain deserves a complete clinical and diagnostic evaluation. PMID:24578939

  20. Detection of the c-myc oncogene product in colonic polyps and carcinomas.

    Science.gov (United States)

    Stewart, J.; Evan, G.; Watson, J.; Sikora, K.

    1986-01-01

    The c-myc oncogene has been implicated in the processes of normal cell proliferation and differentiation. Elevated levels of c-myc mRNA and its gene product (p62c-myc), have been detected in a variety of solid tumours and cultured cel lines. Its precise role in normal cell function and in neoplastic transformation and progression has yet to be elucidated. We have used a monoclonal antibody, raised by peptide immunisation, to determine the distribution by immunoperoxidase staining of the c-myc oncogene product in archival specimens of colonic polyps and carcinomas. Samples from 42 patients with colon carcinoma, 24 with benign polyps and 15 normal colon biopsies were examined. Normal colon revealed maximum staining in the mid-zone of the crypts, corresponding to the zone of differentiation and maturation. The staining was predominantly cytoplasmic. Adenomatous polyps revealed the most intense pattern of staining in areas of dysplastic change. Colonic tumours showed a wide range of staining. Well differentiated tumours contained more cytoplasmic p62c-myc than poorly differentiated tumours. These findings suggest that the c-myc oncogene product may play an important role in the evolution of colonic neoplasia. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:3511934

  1. TfR2 expression in human colon carcinomas.

    Science.gov (United States)

    Calzolari, Alessia; Deaglio, Silvia; Maldi, Elena; Cassoni, Paola; Malavasi, Fabio; Testa, Ugo

    2009-01-01

    Different proteins regulate iron metabolism at the level of various tissues. Among these is a second transferrin receptor (TfR2) that seems to play a key role in the regulation of iron homeostasis. Although TfR2 expression in normal tissues is restricted at the level of the liver, we observed that TfR2 is frequently expressed in cancer cell lines. Taking advantage of this observation we investigated TfR2 expression in primary colon cancers, and showed that this receptor is expressed in about 26% of cases. TfR2 expression in colon cancer is not related to histological grade, but is preferentially associated with mucinous tumors. In colon cancer cell lines, TfR2 is localized in membrane lipid rafts, induces ERK1/ERK2 phosphorylation, when activated by its ligand transferring, and is preferentially expressed during S-M phases of the cell cycle. The presence of TfR2 on the membrane of colon cancer cells may contribute the growth advantage to these cells.

  2. Invasive behavior of ulcerative colitis-associated carcinoma is related to reduced expression of CD44 extracellular domain: comparison with sporadic colon carcinoma

    Directory of Open Access Journals (Sweden)

    Araki Kayo

    2011-04-01

    Full Text Available Abstract Background To elucidate relations of invasion of ulcerative colitis (UC-associated carcinoma with its prognosis, the characteristics of invasive fronts were analyzed in comparison with sporadic colonic carcinomas. Methods Prognoses of 15 cases of UC-associated colonic carcinoma were compared with those of sporadic colon carcinoma cases, after which 75 cases of sporadic invasive adenocarcinoma were collected. Tumor budding was examined histologically at invasive fronts using immunohistochemistry (IHC of pancytokeratin. Expressions of beta-catenin with mutation analysis, CD44 extracellular domain, Zo-1, occludin, matrix matalloproteinase-7, laminin-5γ2, and sialyl Lewis X (LeX were immunohistochemically evaluated. Results UC-associated carcinoma showed worse prognosis than sporadic colon carcinoma in all the cases, and exhibited a tendency to become more poorly differentiated when carcinoma invaded the submucosa or deeper layers than sporadic carcinoma. When the lesions were compared with sporadic carcinomas considering differentiation grade, reduced expression of CD44 extracellular domain in UC-associated carcinoma was apparent. Laminin-5γ2 and sialyl-LeX expression showed a lower tendency in UC-associated carcinomas than in their sporadic counterparts. There were no differences in the numbers of tumor budding foci between the two lesion types, with no apparent relation to nuclear beta-catenin levels in IHC. Conclusions UC-associated carcinoma showed poorer differentiation when the carcinoma invaded submucosa or deeper parts, which may influence the poorer prognosis. The invasive behavior of UC-associated carcinoma is more associated with CD44 cleavage than with basement membrane disruption or sialyl-Lewis-antigen alteration.

  3. Lobular breast carcinoma with colonic metastases: A synchronous diagnosis in a 4-day period

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    Raquel Albero-González

    2017-03-01

    Full Text Available Lobular breast carcinoma involving the colon is a rare condition. In most cases reported in the literature, metastases are detected after a 20-year latency period after the initial diagnosis. Here we describe a case in which metastatic lobular breast carcinoma and colonic metastasis were simultaneously diagnosed—with only 4 days between the two diagnoses. A 55-year-old woman underwent mammography and colonoscopy in the setting of the National Cancer Screening Program. A malignant nodule in the left breast was detected, and core-biopsy revealed an invasive lobular carcinoma. Simultaneously, numerous intestinal micropolyps were sampled. Histological examination of the latter showed tumor cells growing in cords and presenting signet-ring appearance, thereby confirming metastatic breast carcinoma. In cases such as the one described here, pathological diagnosis can be extremely difficult and deep biopsies are required. Metastatic breast cancer involving the colon can be considerably underestimated because of the unspecificity of the clinical manifestations, the long latency period, and diverse radiological findings that can lead to misdiagnosis. We conclude that clinicians should rule out intestinal metastasis in patients diagnosed with breast cancer, especially the lobular type, and presenting non-specific abdominal symptoms.

  4. Feasibility of electronic nose technology for discriminating between head and neck, bladder, and colon carcinomas.

    Science.gov (United States)

    van de Goor, R M G E; Leunis, N; van Hooren, M R A; Francisca, E; Masclee, A; Kremer, B; Kross, K W

    2017-02-01

    Electronic nose (e-nose) technology has the potential to detect cancer at an early stage and can differentiate between cancer origins. Our objective was to compare patients who had head and neck squamous cell carcinoma (HNSCC) with patients who had colon or bladder cancer to determine the distinctive diagnostic characteristics of the e-nose. Feasibility study An e-nose device was used to collect samples of exhaled breath from patients who had HNSCC and those who had bladder or colon cancer, after which the samples were analyzed and compared. One hundred patients with HNSCC, 40 patients with bladder cancer, and 28 patients with colon cancer exhaled through an e-nose for 5 min. An artificial neural network was used for the analysis, and double cross-validation to validate the model. In differentiating HNSCC from colon cancer, a diagnostic accuracy of 81 % was found. When comparing HNSCC with bladder cancer, the diagnostic accuracy was 84 %. A diagnostic accuracy of 84 % was found between bladder cancer and colon cancer. The e-nose technique using double cross-validation is able to discriminate between HNSCC and colon cancer and between HNSCC and bladder cancer. Furthermore, the e-nose technique can distinguish colon cancer from bladder cancer.

  5. Simultaneous quadruple carcinoma of colon Case report and literature review.

    Science.gov (United States)

    Carlomagno, Nicola; Calogero, Armando; Saracco, Michele; Santangelo, Michele; Dodaro, Concetta; Renda, Andrea

    2014-01-01

    Multiple primary malignancies can arise in the large bowel as simultaneous, synchronous and/or metachronous. All tumors must be distant from each other to be considered as primitive, none have to be the result of metastasis from other tumors. We present a case of a 71 years old woman who was admitted to our hospital for a 3-year history of not well defined abdominal pain and hematochezia. The patient had no family history of cancer. Colonoscopy revealed 4 simultaneous tumors located at 4 and 20 cm from the ileocecal valve and at 23,2 and 19 cm from the anal verge. At CT scan there were no distant metastases, neither lymphonode node involvement. A quadruple adenocarcinoma of the colon was confirmed by the pathologist. Patient was operated on total colectomy with ileo-rectal anastomosis. Two or three synchronous tumors of the colon have been already described in literature in about 1,8-14% of cases, but the presence of four simultaneous cancers, as in our case, is very interesting and unusual without an history of FAP or familiar cancer. Comprehensive preoperative study, extensive intraoperative exploration, and radical resection can improve surgical results and survival rate, remaining unquestioned the cause.

  6. Analysis of tumour infiltrating leukocytes in colon cancer carcinoma in a syngeneic rat model

    OpenAIRE

    Borgström, Annelie

    2010-01-01

    Tumour immunity is a balance between immune mediators that promote tumor progression versus mediators that promote tumor rejection. Infiltrating lymphocytes in human colorectal cancer tissues are independent prognostic factors for a better survival and a high number of cytotoxic CD8+ T-cells have been associated with a better prognosis in terms of a longer and disease free survival for the patient. In our syngeneic rat model we induce colon carcinoma subperitoneally by injecting...

  7. Melanocyte Colonization and Pigmentation of Breast Carcinoma: Pathological and Clinical Aspects

    Directory of Open Access Journals (Sweden)

    Marco Mele

    2012-01-01

    Full Text Available Introduction. Melanocyte colonization of breast carcinoma by nonneoplastic melanocytes of epidermal origin is a rare and serious condition first described in 1977. We report on the exceptional clinical and pathological features of this migration phenomenon in a 74-year-old patient. Discussion. The pathogenesis by which melanocyte migration takes place is not known, but a breached basement membrane is considered essential. Conclusion. Histological examination and additional staining of skin are essential to differentiate breast cancer melanosis from malignant melanoma.

  8. Exopolysaccharides extracted from Parachlorella kessleri inhibit colon carcinoma growth in mice via stimulation of host antitumor immune responses.

    Science.gov (United States)

    Ishiguro, Susumu; Uppalapati, Deepthi; Goldsmith, Zachary; Robertson, Dana; Hodge, Jacob; Holt, Hayley; Nakashima, Arashi; Turner, Katie; Tamura, Masaaki

    2017-01-01

    The newly purified extracellular polysaccharides (exopolysaccharides) from Parachlorella kessleri (PCEPS) were evaluated on their antitumor and immunomodulatory effects in cell culture and mouse colon carcinoma peritoneal dissemination model. In two-dimensional cell culture, the PCEPS treatment inhibited cell growth of both murine and human colon carcinoma cells in a dose- and time-dependent manner. In contrast, the growth of mouse splenocytes (SPLs) and bone marrow cells (BMCs) were stimulated by the treatment with PCEPS. The treatment with PCEPS also increased specific subpopulations of the cells in BMCs: antigen presenting cells (CD19+ B cells, 33D1+ dendritic cells and CD68+ macrophage) and CD8+ cytotoxic T cells. In three-dimensional spheroid culture, spheroid growth of CT26 cells co-cultured with HL-60 human neutrophilic promyeloblasts and Jurkat cells (human lymphoblasts), but not THP-1 human monocyte/macrophage was significantly attenuated by PCEPS treatment. In a mouse CT26 colon carcinoma peritoneal dissemination model, intraperitoneal injection of PCEPS (10 mg/kg, twice per week) significantly attenuated the growth of CT26 colon carcinoma in syngeneic mice. The present study suggests that PCEPS inhibits colon carcinoma growth via direct cell growth inhibition and a stimulation of the host antitumor immune responses. Taken together, the current study suggests that exopolysaccharides derived from Parachlorella kessleri contain significant bioactive materials that inhibit colon carcinoma growth.

  9. Combination Gene Therapy for Liver Metastasis of Colon Carcinoma in vivo

    Science.gov (United States)

    Chen, Shu-Hsai; Chen, X. H. Li; Wang, Yibin; Kosai, Ken-Ichiro; Finegold, Milton J.; Rich, Susan S.

    1995-03-01

    The efficacy of combination therapy with a "suicide gene" and a cytokine gene to treat metastatic colon carcinoma in the liver was investigated. Tumor in the liver was generated by intrahepatic injection of a colon carcinoma cell line (MCA-26) in syngeneic BALB/c mice. Recombinant adenoviral vectors containing various control and therapeutic genes were injected directly into the solid tumors, followed by treatment with ganciclovir. While the tumors continued to grow in all animals treated with a control vector or a mouse interleukin 2 vector, those treated with a herpes simplex virus thymidine kinase vector, with or without the coadministration of the mouse interleukin 2 vector, exhibited dramatic necrosis and regression. However, only animals treated with both vectors developed an effective systemic antitumoral immunity against challenges of tumorigenic doses of parental tumor cells inoculated at distant sites. The antitumoral immunity was associated with the presence of MCA-26 tumor-specific cytolytic CD8^+ T lymphocytes. The results suggest that combination suicide and cytokine gene therapy in vivo can be a powerful approach for treatment of metastatic colon carcinoma in the liver.

  10. Poliposis múltiple familiar y carcinoma de colon Multiple familial polyposis and carcinoma of the colon: report of a case

    Directory of Open Access Journals (Sweden)

    María Isabel Villegas

    1989-02-01

    Full Text Available

    La poliposis múltiple familiar (PMF es una enfermedad hereditaria rara pero que, frecuentemente, presenta degeneración maligna. En los pacientes con PMF la edad media de muerte por carcinoma colorrectal es 46 años. La frecuencia de éste después de efectuado el diagnóstico es de 12% en los primeros cinco años, 50% entre los 15 y los 20 años y 100% con posterioridad a los 35 años. El tratamiento del paciente con PMF es la refección del colon; se propone esta cirugía en el momento del diagnóstico debido al alto riesgo de desarrollar carcinoma del colon. Los tipos de tratamiento quirúrgico son: 1 Colectomía total con ileostomía definitiva; 2 colectomía y anastomosis ileorrectal; 3 colectomía, mucosectomía rectal yanastomosis ileoanal. Las indicaciones de cada técnica dependen de la edad del paciente, el número de pólipos en el recto y la presencia O no de carcinoma. Todos los pacientes, independientemente del tratamiento quirúrgico, deben ser estudiados con endoscopia digestiva superior, ya que un alto porcentaje presenta pólipos adenomatosos en estómago y duodeno, que también deben ser resecados. Se presenta el caso de una mujer joven, sin antecedentes familiares claros de PMF, que desarrolló adenocarcinoma del colon 9 años después del diagnóstico Inicial.

    We report the case of a young woman with MFP who developed colonic adenocarcinoma nine years after the initial diagnosis; she had no clear. cut history of MFP. This one is a rare, hereditary disease, with a tendency to malignant degeneration; the frequency of colorectal carcinoma increases from 12% five years after initial diagnosis, to 100% 30 years later. In order to prevent carcinoma, colectomy should be performed as soon as possible after diagnosis. Different surgical

  11. Syndecan-1 deficiency promotes tumor growth in a murine model of colitis-induced colon carcinoma.

    Directory of Open Access Journals (Sweden)

    Adi Binder Gallimidi

    Full Text Available Syndecan-1 (Sdc1 is an important member of the cell surface heparan sulfate proteoglycan family, highly expressed by epithelial cells in adult organisms. Sdc1 is involved in the regulation of cell migration, cell-cell and cell-matrix interactions, growth-factor, chemokine and integrin activity, and implicated in inflammatory responses and tumorigenesis. Gastrointestinal tract represents an important anatomic site where loss of Sdc1 expression was reported both in inflammation and malignancy. However, the biological significance of Sdc1 in chronic colitis-associated tumorigenesis has not been elucidated. To the best of our knowledge, this study is the first to test the effects of Sdc1 loss on colorectal tumor development in inflammation-driven colon tumorigenesis. Utilizing a mouse model of colitis-related colon carcinoma induced by the carcinogen azoxymethane (AOM, followed by the inflammatory agent dextran sodium sulfate (DSS, we found that Sdc1 deficiency results in increased susceptibility to colitis-associated tumorigenesis. Importantly, colitis-associated tumors developed in Sdc1-defficient mice were characterized by increased local production of IL-6, activation of STAT3, as well as induction of several STAT3 target genes that act as important effectors of colonic tumorigenesis. Altogether, our results highlight a previously unknown effect of Sdc1 loss in progression of inflammation-associated cancer and suggest that decreased levels of Sdc1 may serve as an indicator of colon carcinoma progression in the setting of chronic inflammation.

  12. The destruction complex of beta-catenin in colorectal carcinoma and colonic adenoma.

    Science.gov (United States)

    Bourroul, Guilherme Muniz; Fragoso, Hélio José; Gomes, José Walter Feitosa; Bourroul, Vivian Sati Oba; Oshima, Celina Tizuko Fujiyama; Gomes, Thiago Simão; Saba, Gabriela Tognini; Palma, Rogério Tadeu; Waisberg, Jaques

    2016-01-01

    To evaluate the destruction complex of beta-catenin by the expression of the proteins beta-catetenin, adenomatous polyposis coli, GSK3β, axin and ubiquitin in colorectal carcinoma and colonic adenoma. Tissue samples from 64 patients with colorectal carcinoma and 53 patients with colonic adenoma were analyzed. Tissue microarray blocks and slides were prepared and subjected to immunohistochemistry with polyclonal antibodies in carcinoma, adjacent non-neoplastic mucosa, and adenoma tissues. The immunoreactivity was evaluated by the percentage of positive stained cells and by the intensity assessed through of the stained grade of proteins in the cytoplasm and nucleus of cells. In the statistical analysis, the Spearman correlation coefficient, Student's t, χ2, Mann-Whitney, and McNemar tests, and univariate logistic regression analysis were used. In colorectal carcinoma, the expressions of beta-catenin and adenomatous polyposis coli proteins were significantly higher than in colonic adenomas (pcitoplasma e no núcleo das células. Na análise estatística, foram utilizados o coeficiente de correlação de Spearman, os testes t de Student, χ2, Mann-Whitney e de McNemar, e a análise de regressão logística univariada. No carcinoma colorretal, as expressões da betacatenina e da adenomatous polyposis coli foram significativamente maiores do que em adenomas do colo (p<0,001 e p<0,0001, respectivamente). A imunorreatividade das proteínas GSK3β, axina 1 e ubiquitina foi significativamente maior (p=0,03, p=0,039 e p=0,03, respectivamente) no carcinoma colorretal do que no adenoma e na mucosa não neoplásica adjacente. A coloração imuno-histoquímica dessas proteínas não apresentou diferenças significantes em relação às características clinicopatológicas do câncer colorretal e do adenoma. Em adenomas, as menores expressões de betacatenina, axina 1 e GSK3β indicaram que o complexo de destruição da betacatenina estava conservado, enquanto que, no carcinoma

  13. In vitro evaluation of radiolabeled aptamers for colon carcinoma diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Correa, C.R.; Ferreira, I.M; Santos, S.R.; Faria, L.S.; Andrade, A.S.R., E-mail: crisrcorrea@gmail.com, E-mail: antero@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Goes, A.M., E-mail: goes@icb.ufmg.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Inst. de Ciencias Biologicas. Dept. de Imunologia e Bioquimica

    2013-07-01

    Cancer is a leading cause of death worldwide, representing a major public health problem worldwide. Colorectal cancers accounts around 8% of all deaths for cancer in 2008, is the fourth most lethal. Many colorectal cancer markers, such as carcinoembryonic antigen (CEA), A33, and CSA-p, have been studied as the therapeutic targets in preclinical or clinical settings. CEA is a complex intracellular glycoprotein produced by about 90% of colorectal cancers. Since its discovery in 1965, a very large number of studies have been carried out to determine the effectiveness of CEA as clinically useful tumor markers. Aptamers are short single-stranded nucleic acid oligomers (DNA or RNA) that can form specific and complex three-dimensional structures which can bind with high affinity to specific targets, they are functionally equivalent of antibodies. Aptamers have the advantage of being highly specific, relatively small size, and non-immunogenic. The aim of this study was develop anti-CEA aptamers for use as imaging agents. The aptamers are obtained through by SELEX (systematic evolution of ligands by exponential enrichment), in which aptamers are selected from a library of random sequences of synthetic DNA by repetitive binding of the oligonucleotides to target molecule. These aptamers were confirmed to have affinity and specific binding for T84 cell line (target cell), showed by fluorescence microscopic images. Individual aptamers sequences that bound T84 cells were {sup 32}P-radiolabeled and incubated at different concentrations on cell monolayers, to monitor the aptamers affinity binding. The selected aptamers can identify colon cancer cell line. This aptamers could be further developed for early disease detection as radiopharmaceuticals, as well as prognostic markers, of colorectal cancers. (author)

  14. 1,25(OH)2D3 attenuates TGF-β1/β2-induced increased migration and invasion via inhibiting epithelial–mesenchymal transition in colon cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Shanwen; Zhu, Jing; Zuo, Shuai; Ma, Ju; Zhang, Junling; Chen, Guowei; Wang, Xin; Pan, Yisheng; Liu, Yucun; Wang, Pengyuan, E-mail: wangpengyuan2014@126.com

    2015-12-04

    1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) has been reported to inhibit proliferation and migration of multiple types of cancer cells. However, the mechanism underlying its anti-metastasis effect is not fully illustrated. In this study, the effect of 1,25(OH)2D3 on TGF-β1/β2-induced epithelial–mesenchymal transition (EMT) is tested in colon cancer cells. The results suggest that 1,25(OH)2D3 inhibited TGF-β1/β2-induced increased invasion and migration of in SW-480 and HT-29 cells. 1,25(OH)2D3 also inhibited the cadherin switch in SW-480 and HT-29 cells. TGF-β1/β2-induced increased expression of EMT-related transcription factors was also inhibited by 1,25(OH)2D3. 1,25(OH)2D3 also inhibited the secretion of MMP-2 and MMP-9 and increased expression of F-actin induced by TGF-β1/β2 in SW-480 cells. Taken together, this study suggests that the suppression of EMT might be one of the mechanisms underlying the anti-metastasis effect of 1,25(OH)2D3 in colon cancer cells. - Highlights: • TGF-β1/β2-induced model of EMT was used in this study to test the effect of 1,25(OH)2D3 on EMT in colon cancer cells. • 1,25(OH)2D3 inhibited TGF-β1/β2-induced increased migration and invasion. • 1,25(OH)2D3 inhibited TGF-β1/β2-induced increased level of EMT-related transcription factors. • 1,25(OH)2D3 inhibited TGF-β1/β2-induced increased expression of F-actin in SW-480 cells.

  15. Functional Role and Therapeutic Potential of the Pim-1 Kinase in Colon Carcinoma

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    Ulrike Weirauch

    2013-07-01

    Full Text Available PURPOSE: The provirus integration site for Moloney murine leukemia virus 1 (Pim-1 kinase is overexpressed in various tumors and has been linked to poor prognosis. Its role as proto-oncogene is based on several Pim-1 target proteins involved in pivotal cellular processes. Here, we explore the functional relevance of Pim-1 in colon carcinoma. EXPERIMENTAL DESIGN: RNAi-based knockdown approaches, as well as a specific small molecule inhibitor, were used to inhibit Pim-1 in colon carcinoma cells. The effects were analyzed regarding proliferation, apoptosis, sensitization toward cytostatic treatment, and overall antitumor effect in vitro and in mouse tumor models in vivo. RESULTS: We demonstrate antiproliferative, proapoptotic, and overall antitumor effects of Pim-1 inhibition. The sensitization to 5-fluorouracil (5-FU treatment upon Pim-1 knockdown offers new possibilities for combinatorial treatment approaches. Importantly, this also antagonizes a 5-FU-triggered Pim-1 up-regulation, which is mediated by decreased levels of miR-15b, a microRNA we newly identify to regulate Pim-1. The analysis of the molecular effects of Pim-1 inhibition reveals a complex regulatory network, with therapeutic Pim-1 repression leading to major changes in oncogenic signal transduction with regard to p21Cip1/WAF1, STAT3, c-jun-N-terminal kinase (JNK, c-Myc, and survivin and in the levels of apoptosis-related proteins Puma, Bax, and Bcl-xL. CONCLUSIONS: We demonstrate that Pim-1 plays a pivotal role in several tumor-relevant signaling pathways and establish the functional relevance of Pim-1 in colon carcinoma. Our results also substantiate the RNAi-mediated Pim-1 knockdown based on polymeric polyethylenimine/ small interfering RNA nanoparticles as a promising therapeutic approach.

  16. An unusual presentation of multiple cavitated lung metastases from colon carcinoma

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    Iannace Alessandro

    2011-05-01

    Full Text Available Abstract Background Consolidation with or without ground-glass opacity is the typical radiologic finding of lung metastases of adenocarcinoma from the gastrointestinal tract. Lung excavated metastases from gastrointestinal carcinoma are very rare. Case presentation The authors describe an unusual presentation of multiple cavitated lung metastases from colon adenocarcinoma and discuss the outcome of a patient. The absence both of symptoms and other disease localizations, the investigations related to different diagnostic hypotheses and the empirical treatments caused a delay in correct diagnosis. Only a transparietal biopsy revealed the neoplastic origin of nodules. Conclusions This report demonstrates that although lung excavated metastases are described in literature, initial failure to reach a diagnosis is common. We would like to alert clinicians and radiologists to the possibility of unusual atypical features of pulmonary metastases from colon adenocarcinoma.

  17. Over expression of galectin-3 associates with short-term poor prognosis in stage II colon cancer.

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    Huang, Zhiliang; Ai, Zenan; Li, Nan; Xi, Haofeng; Gao, Xucan; Wang, Feng; Tan, Xiaojun; Liu, Haiying

    2016-01-01

    Over expression of galectin-3 (gal-3) has been associated with tumor invasion and distant metastases, but few reports investigated the relation between gal-3 expression and prognosis in stage II colon cancer. We studied the expressions of gal-3, E-cadherin, and vimentin in stage II colon cancer to identify predictive factors of clinical outcome. Clinical and laboratory data from 117 consecutive patients of stage II colon cancer during 2008-2010 were collected and analyzed retrospectively. Expressions of gal-3, E-cadherin, and vimentin in tumor tissue were investigated by immunohistochemistry. Potential correlations between these markers and various clinicopathological parameters as well as clinical outcomes were studied. Human colon cancer cell line SW480 was used to test the epithelial-mesenchymal transition (EMT) inducing effects of gal-3 in vitro. High expression of tumoral gal-3 was associated with tumor size, poor differentiation and negatively related to low E-cadherin expression. Compare with adjacent normal colon tissue, most tumor tissues strongly expressed gal-3 and vimentin, but had lower E-cadherin expression. Univariate analysis showed that expressions of gal-3 and vimentin in tumor were predictors of tumor recurrence and overall survival. Multivariate analysis revealed that tumoral gal-3 expression was the only independent predictor of both tumor recurrence and overall survival after resection. Cell experiments and western blotting showed exogenous gal-3 could induce SW480 cells become more aggressive and express more hallmarks of EMT. Galectin-3 may be a useful marker for identification of poor prognosis in stage II colon cancer. Cell experiments and western blotting showed exogenous gal-3 could induce SW480 cells become more aggressive and express more hallmarks of EMT.

  18. Primary Colonic Signet Ring Cell Carcinoma Presenting Carcinocythemia: An Autopsy Case

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    Ryosuke Misawa

    2008-09-01

    Full Text Available Primary colorectal signet ring cell carcinoma (SRCC is a rare but distinctive type of mucin-producing adenocarcinoma of the large intestine with still controversial clinicopathological features and prognosis. We encountered primary colonic SRCC in a 51-year-old Japanese man with extensive bone metastasis ultimately leading to carcinocythemia before the initiation of chemotherapy and surgical intervention. Three days before death, besides progressive disseminated intravascular coagulation that had been present on admission, hematological examination showed sudden leukocytosis with nonhematopoietic cells that subsequently turned out to be signet ring cells (SRCs. Carcinocythemia, the presence of circulating cancer cells in peripheral blood, is considered to be a rare but an ominous phenomenon occurring in the advanced stage of certain types of cancers, particularly mammary lobular carcinoma. It can be assumed that carcinoma cells lacking intercellular cohesiveness and polarized cell membrane organization, including SRCs as well as lobular carcinoma cells, can readily get access to the peripheral circulation; however, to our knowledge, this is the first report of primary colorectal SRCC that presented carcinocythemia. Extensive bone metastatic sites, in the present case, may have functioned as a reservoir of circulating SRCs.

  19. Benign ulcer of the right colon clinically misdiagnosed as carcinoma: an additional case.

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    Ambrosio, M R; Ginori, A; Mourmouras, V; Mastrogiulio, M G; Barone, A; Rocca, B J

    2012-02-01

    Benign solitary ulcer of the colon is an uncommon lesion that was originally described by Cruveilhier in 1832. Its aetiology remains unknown, and there are no pathognomonic lesions or symptoms. Diagnosis is made by exclusion; in fact, diseases such as specific infections (cytomegalovirus, campylobacter jejuni, entamoeba histolytica), common clinical conditions (acute appendicitis, diverticulitis, intestinal obstruction, inflammatory bowel disease), pharmacotherapy (non-steroidal anti-inflammatory medications, oral contraceptives, dicumarolic agents) and malignancies should be excluded. We describe the case of a 72-year-old patient admitted for acute bloody diarrhoea, originally misdiagnosed as carcinoma by colonscopy. The histological evaluation demonstrated a benign ulcerative lesion.

  20. Thyroid, Renal, and Breast Carcinomas, Chondrosarcoma, Colon Adenomas, and Ganglioneuroma: A New Cancer Syndrome, FAP, or Just Coincidence

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    Ihab Shafek Atta

    2016-01-01

    Full Text Available We are presenting a case associated with papillary thyroid carcinoma, renal cell carcinoma, invasive mammary carcinoma, chondrosarcoma, benign ganglioneuroma, and numerous colon adenomas. The patient had a family history of colon cancer, kidney and bladder cancers, lung cancer, thyroid cancer, leukemia, and throat and mouth cancers. She was diagnosed with colonic villous adenoma at the age of 41 followed by thyroid, renal, and breast cancers and chondrosarcoma at the ages of 48, 64, 71, and 74, respectively. Additionally, we included a table with the most common familial cancer syndromes with one or more benign or malignant tumors diagnosed in our case, namely, FAP, HNPCC, Cowden, Peutz-Jeghers, renal cancer, tuberous sclerosis, VHL, breast/other, breast/ovarian, Carney, Werner’s, Bloom, Li-Fraumeni, xeroderma pigmentosum, ataxia-telangiectasia, osteochondromatosis, retinoblastoma, and MEN2A.

  1. The Prognostic Impact of Protein Expression of E-Cadherin-Catenin Complexes Differs between Rectal and Colon Carcinoma

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    Rolf Aamodt

    2010-01-01

    Full Text Available The E-cadherin-catenin complex provides cell-cell adhesion. In order for a carcinoma to metastasize, cancer cells must let go of their hold of neighboring cells in the primary tumor. The presence of components of the E-cadherin-catenin complex in 246 rectal adenocarcinomas was examined by immunohistochemistry and compared to their presence in 219 colon carcinomas. The expression data were correlated to clinical information from the patients' records. There were statistically significant differences in protein expression between the rectal and the colon carcinomas regarding membranous -catenin, -catenin, p120-catenin, and E-cadherin, as well as nuclear -catenin. In the rectal carcinomas, there was a significant inverse association between the expression of p120-catenin in cell membranes of the primary tumors and the occurrence of local recurrence, while membranous protein expression of -catenin was inversely related to distant metastases.

  2. The Prognostic Impact of Protein Expression of E-Cadherin-Catenin Complexes Differs between Rectal and Colon Carcinoma.

    Science.gov (United States)

    Aamodt, Rolf; Bondi, Johan; Andersen, Solveig Norheim; Bakka, Arne; Bukholm, Geir; Bukholm, Ida R K

    2010-01-01

    The E-cadherin-catenin complex provides cell-cell adhesion. In order for a carcinoma to metastasize, cancer cells must let go of their hold of neighboring cells in the primary tumor. The presence of components of the E-cadherin-catenin complex in 246 rectal adenocarcinomas was examined by immunohistochemistry and compared to their presence in 219 colon carcinomas. The expression data were correlated to clinical information from the patients' records. There were statistically significant differences in protein expression between the rectal and the colon carcinomas regarding membranous beta-catenin, gamma-catenin, p120-catenin, and E-cadherin, as well as nuclear beta-catenin. In the rectal carcinomas, there was a significant inverse association between the expression of p120-catenin in cell membranes of the primary tumors and the occurrence of local recurrence, while membranous protein expression of beta-catenin was inversely related to distant metastases.

  3. 1,25(OH)2D3 attenuates TGF-β1/β2-induced increased migration and invasion via inhibiting epithelial-mesenchymal transition in colon cancer cells.

    Science.gov (United States)

    Chen, Shanwen; Zhu, Jing; Zuo, Shuai; Ma, Ju; Zhang, Junling; Chen, Guowei; Wang, Xin; Pan, Yisheng; Liu, Yucun; Wang, Pengyuan

    1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) has been reported to inhibit proliferation and migration of multiple types of cancer cells. However, the mechanism underlying its anti-metastasis effect is not fully illustrated. In this study, the effect of 1,25(OH)2D3 on TGF-β1/β2-induced epithelial-mesenchymal transition (EMT) is tested in colon cancer cells. The results suggest that 1,25(OH)2D3 inhibited TGF-β1/β2-induced increased invasion and migration of in SW-480 and HT-29 cells. 1,25(OH)2D3 also inhibited the cadherin switch in SW-480 and HT-29 cells. TGF-β1/β2-induced increased expression of EMT-related transcription factors was also inhibited by 1,25(OH)2D3. 1,25(OH)2D3 also inhibited the secretion of MMP-2 and MMP-9 and increased expression of F-actin induced by TGF-β1/β2 in SW-480 cells. Taken together, this study suggests that the suppression of EMT might be one of the mechanisms underlying the anti-metastasis effect of 1,25(OH)2D3 in colon cancer cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. [In vitro and in vivo effects of mango pulp (Mangifera indica cv. Azucar) in colon carcinogenesis].

    Science.gov (United States)

    Corrales-Bernal, Andrea; Amparo Urango, Luz; Rojano, Benjamín; Maldonado, Maria Elena

    2014-03-01

    Mango pulp contains ascorbic acid, carotenoids, polyphenols, terpenoids and fiber which are healthy and could protect against colon cancer. The aim of this study was to evaluate the antiproliferative and preventive capacity of an aqueous extract of Mangifera indica cv. Azúcar on a human colon adenocarcinoma cell line (SW480) and in a rodent model of colorectal cancer, respectively. The content of total phenolics, flavonoids and carotenoids were also analyzed in the extract. SW480 cell growth was inhibited in a dose and time dependent manner by 22.3% after a 72h exposure to the extract (200 µg/ mL). Colon carcinogenesis was initiated in Balb/c mice by two intra-peritoneal injections of azoxymethane (AOM) at the third and fourth week of giving mango in drinking water (0.3%, 0.6%, 1.25%). After 10 weeks of treatment, in the colon of mice receiving 0.3% mango, aberrant crypt foci formation was inhibited more than 60% (p=0,05) and the inhibition was dose-dependent when compared with controls receiving water. These results show that mango pulp, a natural food, non toxic, part of human being diet, contains bioactive compounds able to reduce growth of tumor cells and to prevent the appearance of precancerous lesions in colon during carcinogenesis initiation.

  5. Promoter hypermethylation mediated downregulation of FBP1 in human hepatocellular carcinoma and colon cancer.

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    Mingquan Chen

    Full Text Available FBP1, fructose-1,6-bisphosphatase-1, a gluconeogenesis regulatory enzyme, catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and inorganic phosphate. The mechanism that it functions to antagonize glycolysis and was epigenetically inactivated through NF-kappaB pathway in gastric cancer has been reported. However, its role in the liver carcinogenesis still remains unknown. Here, we investigated the expression and DNA methylation of FBP1 in primary HCC and colon tumor. FBP1 was lowly expressed in 80% (8/10 human hepatocellular carcinoma, 66.7% (6/9 liver cancer cell lines and 100% (6/6 colon cancer cell lines, but was higher in paired adjacent non-tumor tissues and immortalized normal cell lines, which was well correlated with its promoter methylation status. Methylation was further detected in primary HCCs, gastric and colon tumor tissues, but none or occasionally in paired adjacent non-tumor tissues. Detailed methylation analysis of 29 CpG sites at a 327-bp promoter region by bisulfite genomic sequencing confirmed its methylation. FBP1 silencing could be reversed by chemical demethylation treatment with 5-aza-2'-deoxycytidine (Aza, indicating direct epigenetic silencing. Restoring FBP1 expression in low expressed cells significantly inhibited cell growth and colony formation ability through the induction of G2-M phase cell cycle arrest. Moreover, the observed effects coincided with an increase in reactive oxygen species (ROS generation. In summary, epigenetic inactivation of FBP1 is also common in human liver and colon cancer. FBP1 appears to be a functional tumor suppressor involved in the liver and colon carcinogenesis.

  6. Intramedullary spinal cord metastasis from colonic carcinoma presenting as Brown-Sequard syndrome: a case report

    LENUS (Irish Health Repository)

    Kaballo, Mohammed A

    2011-08-02

    Abstract Introduction Intramedullary spinal cord metastasis is very rare. The majority are discovered incidentally during autopsy. Most symptomatic patients present with rapidly progressive neurological deficits and require immediate examination. Few patients demonstrate features of Brown-Séquard syndrome. Radiotherapy is the gold-standard of therapy for Intramedullary spinal cord metastasis. The overall prognosis is poor and the mortality rate is very high. We present what is, to the best of our knowledge, the first case of Intramedullary spinal cord metastasis of colorectal carcinoma presenting as Brown-Séquard syndrome. Case presentation We present the case of a 71-year-old Caucasian man with colonic adenocarcinoma who developed Intramedullary spinal cord metastasis and showed features of Brown-Séquard syndrome, which is an uncommon presentation of Intramedullary spinal cord metastasis. Conclusion This patient had an Intramedullary spinal cord metastasis, a rare form of metastatic disease, secondary to colonic carcinoma. The metastasis manifested clinically as Brown-Séquard syndrome, itself a very uncommon condition. This syndrome is rarely caused by intramedullary tumors. This unique case has particular interest in medicine, especially for the specialties of medical, surgical and radiation oncology. We hope that it will add more information to the literature about these entities.

  7. Laminin-5 γ2 Chain Expression Correlates with Unfavorable Prognosis in Colon Carcinomas

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    C. Lenander

    2001-01-01

    Full Text Available Expression of the γ2 chain at the invasive front of different tumors has indicated an important role for laminin-5 in cell migration during tumor invasion and tissue remodeling. As there is considerable need for reliable invasion and prognostic markers we evaluated the correlation of laminin-5 γ2 chain expression with clinicopathologic parameters and patient survival in 93 primary colon carcinomas. Epithelial cells of normal mucosa were consistently negative for staining. In contrast, positive cytoplasmic staining was observed in 89 tumors (96%. Twenty-four (26% cases were scored as sparse, 34 (37% as moderate, and 31 (33% as frequent γ2 chain expression. There was a significant association of laminin-5 γ2 chain expression and local invasiveness of colon carcinomas according to Dukes stage (A-C (p = 0.001 and tumor budding (p < 0.001. A statistical significance could also be noted in decreasing tumor differentiation (p < 0.001 and correlation to tumor size (p = 0.032. No correlation was observed to tumor site. Univariate analysis identified laminin-5 (p = 0.010, tumor differentiation (p = 0.006 and Dukes grade (p < 0.001 as significant variables in predicting prognosis. However, by multivariate analyses, this study could not demonstrate that laminin-5 γ2 chain expression is an independent predictive factor for survival. The results indicate that laminin-5 γ2 chain expression is up-regulated during the progression of human colon cancer and that it plays a role in the aggressiveness of these tumors. Demonstration of laminin-5 γ2 chain positivity also facilitates detection of individual cells or minor cell clusters invading the surrounding stroma.

  8. Duodenal seromyectomy in the management of adherent colonic carcinoma in elderly patients.

    Science.gov (United States)

    Sharma, P; Klaasen, H

    1997-08-01

    To determine if partial denudation of the duodenum by seromyectomy can achieve tumour clearance in elderly patients with adherent primary colonic carcinoma. A case series. An urban tertiary care centre. Seven elderly patients with Dukes' class C primary adenocarcinoma of the ascending colon adherent to the duodenum but without distant metastases. The follow-up ranged from 29 to 41 months. Right hemicolectomy and seromyectomy of the duodenum at the site of adhesion. Patient survival and tumour recurrence. One patient died 29 months postoperatively of myocardial infarction but without tumour recurrence. Another patient had a solitary metastasis in the right liver lobe 7 months postoperatively. She was disease free 34 months after a right hemihepatectomy. The other 5 patients were alive and disease free at their last follow-up. Duodenal seromyectomy with postoperative chemotherapy for locally advanced adherent colonic cancer seems to be an acceptable management strategy for elderly patients in whom major en bloc resections present a greater than average risk of death.

  9. CELLULAR BASIS FOR DIFFERENTIAL SENSITIVITY TO CISPLATIN IN HUMAN GERM-CELL TUMOR AND COLON-CARCINOMA CELL-LINES

    NARCIS (Netherlands)

    SARK, MWJ; TIMMERBOSSCHA, H; MEIJER, C; UGES, DRA; SLUITER, WJ; PETERS, WHM; MULDER, NH; DEVRIES, EGE

    Cisplatin (CDDP) resistance mechanisms were studied in a model of three germ cell tumour and three colon carcinoma cell lines representing intrinsically CDDP-sensitive and -resistant tumours respectively. The CDDP sensitivity of the cell lines mimicked the clinical situation. The glutathione levels

  10. Histopathological Analysis of High {sup 18}F-FDG Uptake in Meniscoid Ulcer of Colon Carcinoma: Report of A Case

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    Bahk, Yong Whee [Sung Ae Hospital, Seoul (Korea, Republic of); Jang, Ja June [Seoul National University School of Medicine, Seoul (Korea, Republic of)

    2008-04-15

    Prominent 18F-fluorodeoxyglucose (18F-FDG) accumulation has been reported to occur in meniscoid ulcer of gastric carcinoma. A mouse-model study carried out by Kubota et al. revealed that inflammatory cells, particularly macrophages, in necrotic tumor accumulates 18F-FDG more avidly than viable tumor cells. A search of literature failed to disclose earlier publication reporting histological study on such high 18F-FDG metabolism in patient with ulcerating colon cancer. This communication presents prominent 18FDG uptake observed in relation with chronic inflammation in meniscoid ulcer of sigmoid colon carcinoma. Cross correlation of PET findings with those of CT scan and colonoscopy showed that the high 18F-FDG uptake was localized to ulcerated part of tumor and not in heaved-up border that was not ulcerated. Histopathology of removed tumor revealed that the denuded bottom of ulcer consisted of a thick layer of submucosal tissue diffusely infiltrated with inflammatory cells. The meniscoid malignant ulcer, originally described in 1921 by Carman and re-studied in detail by Kirklin, is created by barium filling of crescent defect of ulcerating gastric carcinoma. Since then the sign has long been appreciated as a clue of ulcerating gastric carcinoma. In the meantime, the sign has also been reported to occur in the carcinomas of the esophagus by Gloyna et al. and the colon by Siskind and Burrell.

  11. SN38 conjugated hyaluronic acid gold nanoparticles as a novel system against metastatic colon cancer cells.

    Science.gov (United States)

    Hosseinzadeh, Hosniyeh; Atyabi, Fatemeh; Varnamkhasti, Behrang Shiri; Hosseinzadeh, Reza; Ostad, Seyed Nasser; Ghahremani, Mohammad Hossein; Dinarvand, Rassoul

    2017-06-30

    Combination of chemotherapy and photothermal therapy has been proposed for better treatment of metastatic colon cancer. In this study SN38, a highly potent cytotoxic agent, was conjugated to negatively charged hyaluronic acid (HA), which was deposited on the surface of the positively charged gold nanoparticles via electrostatic interaction. The drug conjugation and its interaction with gold nanoparticles were verified by 1 H NMR and UV-vis spectroscopies, respectively. The prepared SN38-HA gold NPs are negatively charged spherical nanoparticles with an average size of 75±10nm. In vitro release study revealed that drug release in acidic conditions (pH 5.2) was faster than that in physiological pH. Red light emitting diode (LED, 630nm, 30mW) was used as a light source for photothermal experiments. The drug release in acidic conditions was increased up to 30% using red LED illumination (6min) in comparison with experiment carried out indark. The cytotoxicity study on MUC1 positive HT29, SW480 colon cancer cells and MUC1 negative CHO cells, showed higher toxicity of the nanoparticles on HT29 and SW480 cell lines compared to CHO cells. Confocal microscopy images along with flow cytometry analysis confirm the cytotoxicity results. The incubation time for reaching IC50 decreases from 48h to 24h by LED illumination after nanoparticle treatment. Migratory potential of the HT29 and SW480 cell lines was reduced by co-application of SN38-HA gold NPs and LED radiation. Also anti-proliferative study indicates that LED radiation has increased the cytotoxicity of the nanoparticles and this effect is remained up to 8days. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Heterogeneity-related anticancer therapy response differences in metastatic colon carcinoma: new hints to tumor-site-based personalized cancer therapy.

    Science.gov (United States)

    Pan, Weihuo; Huang, Shuru; Zhang, Jianwei; Zhao, Bo; Wang, Haohao; Liu, Fanlong; Jin, Ketao; Mou, Xiaozhou

    2013-01-01

    Heterogeneity in primary tumor and related metastases may result in different response to anticancer therapy. Previous work revealed that there were heterogeneity in primary colon carcinoma and matched lymphatic and hepatic metastases. Whether such heterogeneity in primary colon carcinoma and corresponding lymphatic and hepatic metastases would result in different response to anticancer therapy is unknown. To investigate whether the heterogeneity in primary colon carcinoma and matched lymphatic and hepatic metastases would result in different response to anticancer therapy, patient-derived tumor tissue (PDTT) xenograft models of colon carcinoma with lymphatic and hepatic metastases were used to evaluate the response to VEGF-targeted therapy (bevacizumab) in combination with chemotherapy (capecitabine). All xenografts of primary colon carcinoma and corresponding lymphatic and hepatic metastases in nude mice responded to VEGF-targeted therapy in combination with chemotherapy. However, chemotherapy alone resulted in significantly higher tumor growth inhibition rate in xenogfafts of primary colon carcinoma than that of corresponding lymphatic and hepatic metastasis (p response rate to chemotherapy and to VEGF-targeted therapy in combination with chemotherapy. This study provides us new hints to tumor-site-based personalized cancer therapy in metastatic colon carcinoma.

  13. Inhibitory effect of emodin on fatty acid synthase, colon cancer proliferation and apoptosis.

    Science.gov (United States)

    Lee, Kyung Ha; Lee, Myung Sun; Cha, Eun Young; Sul, Ji Young; Lee, Jin Sun; Kim, Jin Su; Park, Jun Beom; Kim, Ji Yeon

    2017-04-01

    Fatty acid synthase (FASN) is a key anabolic enzyme for de novo fatty acid synthesis, which is important in the development of colon carcinoma. The high expression of FASN is considered a promising molecular target for colon cancer therapy. Emodin, a naturally occurring anthraquinone, exhibits an anticancer effect in various types of human cancer, including colon cancer; however, the molecular mechanisms remain to be fully elucidated. Cell viability was evaluated using a Cell Counting Kit‑8 assay. The apoptosis rate of cells was quantified via flow cytometry following Annexin V/propidium iodide staining. FASN activity was measured by monitoring oxidation of nicotinamide adenine dinucleotide phosphate at a wavelength of 340 nm, and intracellular free fatty acid levels were detected using a Free Fatty Acid Quantification kit. Western blot analysis and reverse transcription‑polymerase chain reaction were used to detect target gene and protein expression. The present study was performed to investigate whether the gene expression of FASN and its enzymatic activity are regulated by emodin in a human colon cancer cell line. Emodin markedly inhibited the proliferation of HCT116 cells and a higher protein level of FASN was expressed, compared with that in SW480, SNU-C2A or SNU‑C5 cells. Emodin significantly downregulated the protein expression of FASN in HCT116 cells, which was caused by protein degradation due to elevated protein ubiquitination. Emodin also inhibited intracellular FASN enzymatic activity and reduced the levels of intracellular free fatty acids. Emodin enhanced antiproliferation and apoptosis in a dose‑ and time‑dependent manner. The combined treatment of emodin and cerulenin, a commercial FASN inhibitor, had an additive effect on these activities. Palmitate, the final product of the FASN reaction, rescued emodin‑induced viability and apoptosis. In addition, emodin altered FASN‑involved signaling pathways, including phosphatidylinositol 3

  14. Predictive gene signatures: molecular markers distinguishing colon adenomatous polyp and carcinoma.

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    Janice E Drew

    Full Text Available Cancers exhibit abnormal molecular signatures associated with disease initiation and progression. Molecular signatures could improve cancer screening, detection, drug development and selection of appropriate drug therapies for individual patients. Typically only very small amounts of tissue are available from patients for analysis and biopsy samples exhibit broad heterogeneity that cannot be captured using a single marker. This report details application of an in-house custom designed GenomeLab System multiplex gene expression assay, the hCellMarkerPlex, to assess predictive gene signatures of normal, adenomatous polyp and carcinoma colon tissue using archived tissue bank material. The hCellMarkerPlex incorporates twenty-one gene markers: epithelial (EZR, KRT18, NOX1, SLC9A2, proliferation (PCNA, CCND1, MS4A12, differentiation (B4GANLT2, CDX1, CDX2, apoptotic (CASP3, NOX1, NTN1, fibroblast (FSP1, COL1A1, structural (ACTG2, CNN1, DES, gene transcription (HDAC1, stem cell (LGR5, endothelial (VWF and mucin production (MUC2. Gene signatures distinguished normal, adenomatous polyp and carcinoma. Individual gene targets significantly contributing to molecular tissue types, classifier genes, were further characterised using real-time PCR, in-situ hybridisation and immunohistochemistry revealing aberrant epithelial expression of MS4A12, LGR5 CDX2, NOX1 and SLC9A2 prior to development of carcinoma. Identified gene signatures identify aberrant epithelial expression of genes prior to cancer development using in-house custom designed gene expression multiplex assays. This approach may be used to assist in objective classification of disease initiation, staging, progression and therapeutic responses using biopsy material.

  15. Metastatic breast carcinoma uncovered in an otherwise unremarkable “random colon biopsy”

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    Mike Black

    2016-06-01

    Full Text Available Breast cancer is one of the most devastating cancers afflicting women, being a main cause of cancer related death. Approximately 50% of these patients have developed regional or distant metastases at the time of diagnosis; hence, an early diagnosis and surgery with indicated neoadjuvant therapy are crucial in eradicating this disease and improving patient survival. A significant percentage of patients, even after initial satisfactory tumor removal, still face the threat of metastatic diseases which could plague a wide spectrum of body sites such as bones, lungs, central nervous system, liver and gastrointestinal tract (mostly upper gastrointestinal locations. Colonic and anorectal involvement by metastatic breast cancer has been less frequently reported in disseminated diseases. Typically, metastatic disease presents as a mass, enteric stenosis, or obstruction. Rare cases, however, may not form an endoscopically or radiologically recognizable lesion, and thus could be overlooked. Here we report a unique case of random colon biopsies in a patient presenting with epigastric pain, whose stomach biopsy showed Helicobacter pylori-associated chronic active gastritis. No colonoscopic lesion was present; however, microscopic examination of the “random biopsy” revealed scattered single and small clusters of tumor cells involving the lamina propria of the colonic mucosa, morphologically and immunophenotypically consistent with metastatic disease from breast carcinoma. The clinical presentation and histopathology of the case were reviewed and compared with limited cases reported in the literature. We conclude that high levels of suspicion and alertness are essential to identify occult microscopic gastrointestinal metastatic breast cancer in the absence of a grossly appreciable lesion.

  16. Colon Carcinoma with Unusual Metastasis to the Esophagus Manifesting as Multiple Nodules and Dysphagia: Management with Systemic Chemotherapy

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    Pankaj G. Vashi

    2012-07-01

    Full Text Available We present here the rare clinical case of a 44-year-old gentleman with metastasis from colon carcinoma to the esophagus presenting with multiple nodules and dysphagia, which was successfully managed with systemic chemotherapy. The patient presented at our institution with 3-month history of dysphagia almost 4 years after being operated for stage III carcinoma in the sigmoid colon. Endoscopic findings showed multiple nodules at the gastroesophageal junction and mid esophagus. Histological features and immunostains confirmed the diagnosis of metastatic colon carcinoma. Because of evidence of extensive metastatic disease in the spine and liver requiring systemic therapy, the patient was treated with chemotherapy with irinotecan and cetuximab, with subsequent improvement in tumor markers, liver metastasis and symptoms of dysphagia. Even though repeat endoscopy showed no improvement in esophageal nodules, the overall response to chemotherapy was positive. In conclusion, we present a very rare, previously unreported case of metastases from colon cancer to the esophagus presenting as non-obstructive nodules and dysphagia that responded to systemic chemotherapy.

  17. L-Fucose as a terminal sugar in cellular glycoconjugates of colonic carcinoma

    Directory of Open Access Journals (Sweden)

    Sargazei GH

    2008-10-01

    staining intensity for L-fucose between tumoral cells of different grades of colon carcinoma (p<0.001. Results show that the degree of UEA lectin binding to cancer cells is lower in the cytoplasm and nucleus and higher in the extracellular matrix in tumors, with the degree increasing with histopathological grade. Furthermore, staining intensity differs in different portions of cancer cells."n"n Conclusions: The increased staining intensity of L-fucose in the extracellular matrix of colon carcinoma is a reflection of the aberrant protein glycosylation pathway in neoplasia. "nKeywords: Colon, adenocarcinoma, lectin, neoplsia, grading, glycoconjugate.

  18. Detection of the BRAF V600E mutation in colon carcinoma: critical evaluation of the imunohistochemical approach.

    Science.gov (United States)

    Lasota, Jerzy; Kowalik, Artur; Wasag, Bartosz; Wang, Zeng-Feng; Felisiak-Golabek, Anna; Coates, Tiffany; Kopczynski, Janusz; Gozdz, Stanislaw; Miettinen, Markku

    2014-09-01

    Recently BRAF V600E mutant-specific antibody (clone VE1) became available to immunohistochemically pinpoint the occurrence of these BRAF-mutant proteins in different tumors, such as colon carcinoma. Detection of BRAF mutations is important for the accurate application of targeted therapy against BRAF serine-threonine kinase activation. In this study, we evaluated 113 colon carcinomas including 95 primary and 27 metastatic tumors with the VE1 antibody using Leica Bond-Max automated immunohistochemistry. To ensure comprehensive BRAF V600E mutation detection, all cases were evaluated using 4 molecular methods (Sanger sequencing, the Cobas 4800 BRAF V600 Mutation Test, BRAF V600 allele-specific polymerase chain reaction, and BRAF V600 quantitative polymerase chain reaction) with nearly 100% concordance. Molecular and immunohistochemical studies were blinded. Furthermore, all cases were evaluated for KRAS and NRAS mutations as parameters mutually exclusive with BRAF mutations offering parallel evidence for BRAF mutation status. Strong to moderate VE1 positivity was seen in 34 tumors. Twelve colon carcinomas showed weak VE1 immunohistochemical staining, and 67 were entirely negative. An identical c.1799T>A single nucleotide substitution leading to the BRAF V600E mutation was identified in 27 of 113 (24%) colon carcinomas. A majority of BRAF-mutant tumors were located in the right side of the colon and had mismatch-repair deficiency. V600E mutation-negative carcinomas were more often sigmoid tumors and usually showed intact mismatch-repair proteins and KRAS or NRAS mutations. The sensitivity and specificity of positive results (strong to moderate staining) of VE1 immunohistochemistry were 85% and 68%, respectively. If any positivity would be considered, then the specificity declined to 51% with no significant improvement of sensitivity. Therefore, only strong positivity should be considered when using the VE1 antibody and Leica Bond-Max automated immunohistochemistry with

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

    Science.gov (United States)

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

    2014-01-01

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

  20. Cyclic AMP-independent secretion of mucin by SW1116 human colon carcinoma cells. Differential control by Ca2+ ionophore A23187 and arachidonic acid

    National Research Council Canada - National Science Library

    Yedgar, S; Eidelman, O; Malden, E; Roberts, D; Etcheberrigaray, R; Goping, G; Fox, C; Pollard, H B

    1992-01-01

    The regulation of mucin secretion by SW1116 human colon carcinoma cells has been studied using monoclonal antibody 19-9, which has previously been used to detect mucin in the serum of cancer and cystic fibrosis patients...

  1. Nano-engineering of biomedical prednisolone liposomes: evaluation of the cytotoxic effect on human colon carcinoma cell lines.

    Science.gov (United States)

    Lorente, Cristina; Arias, José L; Cabeza, Laura; Ortiz, Raúl; Prados, José C; Melguizo, Consolación; Delgado, Ángel V; Clares-Naveros, Beatriz

    2018-01-30

    Liposomes have attracted the attention of researchers due to their potential to act as drug delivery systems for cancer treatment. The present investigation aimed to develop liposomes loaded with prednisolone base and the evaluation of the antiproliferative effect on human colon carcinoma cell lines. Liposomes were elaborated by following a reproducible thin film hydration technique. The physicochemical characterization of liposomes included photon correlation spectroscopy, microscopy analysis, Fourier transform infrared spectroscopy, rheological behaviour and electrophoresis. On the basis of these data and drug loading values, the best formulation was selected. Stability and drug release properties were also tested. Resulting liposomes exhibited optimal physicochemical and stability properties, an excellent haemocompatibility and direct antiproliferative effect on human colon carcinoma T-84 cell lines. This study shows direct antitumour effect of prednisolone liposomal formulation, which opens the door for liposomal glucocorticoids as novel antitumour agents. © 2018 Royal Pharmaceutical Society.

  2. Primary peritoneal serous papillary carcinoma (PSPC involving ovary and colon: Management and Treatment

    Directory of Open Access Journals (Sweden)

    Leanza V

    2013-05-01

    Full Text Available We present a case report of a 47-year-old woman who was admitted to our University-Hospital following diagnosis of pelvic mass. Abdominal examination revealed a tender, palpable mass on the right iliac region. At the gynecological examination uterus was regular in size. On the left side of the uterus a mass of 9 cm was observed; its surface was irregular and no mobility was found. Abdominal CT and NMR revealed massive ascites, omental cake and increased volume of both ovaries. Patient underwent longitudinal suprombelical-pubic laparotomy. After opening abdominal cavity, a free-fluid sample was taken and the results were positive for malignant cells. Typical neoplastic localizations on both ovaries, Douglas’ peritoneum, rectum, sigmoid colon and omentum were observed. Extemporaneous histological examination diagnosed a peritoneal serous papillary carcinoma. Hysterectomy with salpingo oophorectomy, total omentectomy, appendectomy, pelvic and lumbo-aortic lymphadenectomy was performed. Retroperitoneal approach to remove the whole Douglas’ peritoneum together with the pouch malignant localizations was done. Sigmoid colon and rectum were resected. A latero-terminal anastomosis with stapler was performed. All the visible abdominal maligant lesions were cut out. No transfusion was necessary. The postoperative course was regular and after seven days the patient was discharged. Chemotherapy ended the therapeutic management (six cycles of carboplatin and paclitaxel. After one year the patient is in good health and instrumental investigations (Ultrasounds, TC and NMR are negative for recurrence. Such a case is very interesting for the discrepancy between slight symptoms and severity of the disease, the solution of which was very complex requiring a skillful polyspecialized oncological team.

  3. Cytotoxic, antimigratory, pro-and antioxidative activities of extracts from medicinal mushrooms on colon cancer cell lines

    Directory of Open Access Journals (Sweden)

    Šeklić Dragana S.

    2016-01-01

    Full Text Available Methanol extracts of five commercially available mushroom species (Phellinus linteus (Berk. et Curt Teng, Cordyceps sinensis (Berk. Sacc., Lentinus edodes (Berk. Pegler, Coprinus comatus (O. F. Müll. Pers. and Ganoderma lucidum (Curtis P. Karst, traditionally used as anticancer agents, were evaluated in vitro for their total phenol and flavonoid contents, cytotoxic and antimigratory activities and antioxidant/prooxidant effects on colon cancer cell lines (HCT-116 and SW-480. Spectrophotometric methods were used for the determination of total phenol content, flavonoid concentrations and DPPH activity of the extracts. Cytotoxic activity was measured by the MTT assay. The antimigratory activity of extracts was determined using the Transwell assay and immunofluorescence staining of β-catenin. The prooxidant/antioxidant status was followed by measuring the superoxide anion radical (O2•-, nitrite and reduced glutathione (GSH concentrations. Our results show that the highest phenolic and flavonoid content was found in P. linteus, and its DPPH-scavenging capacity was significantly higher than in other samples. The P. linteus extract significantly decreased cell viability of both tested cancer cell lines. All other extracts selectively inhibited SW-480 cell viability, but did not show significant cytotoxic activity. The mushroom extracts caused changes in the prooxidant/antioxidant status of cells, inducing oxidative stress. All extracts tested on HCT-116 cells demonstrated significant antimigratory effects, which correlated with increased production of O2•- and a reduced level of β-catenin protein expression, while only P. linteus showed the same effect on SW-480 cells. The results of the present research indicate that the mushroom extracts causes oxidative stress which has a pronounced impact on the migratory status of colon cancer cell lines. [Projekat Ministarstva nauke Republike Srbije, br. III41010

  4. Comparison of laparoscopic peritoneal vaginoplasty and sigmoid colon vaginoplasty performed during radical surgery for primary vaginal carcinoma

    OpenAIRE

    Yao, Fengqiu; Zhao, Weidong; Chen, Gang; Zhang, Aijun; Sun, Fanglin; Hu, Weiping; Ling, Bin

    2014-01-01

    Background Radical surgery of primary vaginal carcinoma typically involves partial or complete resection of the vagina, and young patients in particular can experience sexual dysfunction after surgery. Vaginoplasty is mandatory for this population, multiple vaginal reconstructive techniques have been reported. Here we attempted to determine whether the peritoneum is a feasible alternative to the sigmoid colon in vaginoplasty performed during radical surgery. Methods Between February 2005 and ...

  5. Identification of the interplay between SOX9 and S100P in the metastasis and invasion of colon carcinoma.

    Science.gov (United States)

    Shen, Zhiyong; Deng, Haijun; Fang, Yuan; Zhu, Xianjun; Ye, Geng-Tai; Yan, Li; Liu, Hao; Li, Guoxin

    2015-08-21

    Elevated expression of S100P has been detected in several tumor types and suggested to be responsible for tumor metastasis and invasion, but the upstream regulatory mechanisms promoting S100P overexpression are largely unknown. Here, we report that SOX9 was predicted and verified as a transcription factor of S100P. SOX9 and S100P were both overexpressed in colon cancer. SOX9 bound to and activated the S100P promoter. Knockdown of SOX9 expression down-regulated S100P expression, resulting in reduced invasiveness and metastasis of colon cancer cells by inhibiting the activation of receptor for advanced glycation end products (RAGE)/ERK signaling and epithelial-mesenchymal transition (EMT). Further, decreased expression of SOX9 dramatically inhibited the tumor growth and peritoneal metastasis in nude mice. More importantly, S100P was found to be critical for SOX9-mediated metastasis and invasion in colon cancer. Knockdown of S100P in SOX9-overexpressing colon cancer cells dramatically suppressed metastasis and invasion both in vitro and in mice. We also detected SOX9 and S100P expression in a tissue microarray with 90 colon cancer cases to provide their clinical relevance. There was a strong correlation between SOX9 and S100P expression in colon carcinomas. In conclusion, our results suggest that SOX9 promotes tumor metastasis and invasion through regulation of S100P expression.

  6. Proteomics of differential extraction fractions enriched for chromatin-binding proteins from colon adenoma and carcinoma tissues

    DEFF Research Database (Denmark)

    Knol, Jaco C; de Wit, Meike; Albrethsen, Jakob

    2014-01-01

    of colorectal cancer (CRC) progression. METHODS: CB protein-containing fractions were biochemically extracted from human colorectal tissues, including carcinomas with chromosomal instability (CIN), carcinomas with microsatellite instability (MIN), and adenomas. The CB proteins were subjected to label-free LC......BACKGROUND: Altered nuclear and genomic structure and function are hallmarks of cancer cells. Research into nuclear proteins in human tissues could uncover novel molecular processes in cancer. Here, we examine biochemical tissue fractions containing chromatin-binding (CB) proteins in the context......-MS/MS and the data were analyzed by bioinformatics. RESULTS: Over 1700 proteins were identified in the CB fraction from colonic tissues, including 938 proteins associated with nuclear annotation. Of the latter, 169 proteins were differential between adenomas and carcinomas. In this adenoma...

  7. Adjuvant intraoperative photodynamic therapy (AIOPDT) after photosensitization with mTHPC in a CC531 colon carcinoma model in mice

    Science.gov (United States)

    Winkler, Steffi; Prosst, Ruediger L.; Stern, Josef; Rheinwald, Markus; Haase, Thomas; Herfarth, Christian; Gahlen, Johannes

    2001-01-01

    The effectiveness of PDT as an adjuvant alternative therapy method for diverse malignant tumors has been investigated in numerous studies. The therapeutic benefit and extent of side effects is mainly determined by the applied photoactive substance. The second generation photosensitizer (PS) mTHPC is capable of causing selective tumor cell death in colon carcinoma when combined with laser irradiation of a PS specific wavelength. Our study revealed PDT with mTHPC as an efficient adjuvant intraoperative modality after R1/R2 resection of a subcutaneously implanted colon tumor. There was a significant increase of postoperative recurrence-free survival time using PDT compared to a control group in a colon cancer model in nude mice. The accumulation of the PS determined by point spectrometry showed a high tumor-selectivity in the tumor, tumor bed, and overlying skin compared to muscle tissue as reference parameter.

  8. Antiproliferative effect of chitosan-added kimchi in HT-29 human colon carcinoma cells.

    Science.gov (United States)

    Kong, Chang-Suk; Bahn, Young-Eun; Kim, Boh-Kyung; Lee, Kang-Yoon; Park, Kun-Young

    2010-02-01

    The anticancer effects of chitosan-added kimchi were investigated by using an in vitro cellular system with HT-29 human colon carcinoma cells. Two different kinds of chitosan-soluble chitosan with a 90% degree of deacetylation and 3 cps viscosity and nonsoluble chitosan with a 95% degree of deacetylation and 22 cps viscosity-were used as sub-ingredients to increase anticancer effects of kimchi. The soluble chitosan-added kimchi (SK) and nonsoluble chitosan-added kimchi (NK) were stronger growth inhibitors in HT-29 cells than the control kimchi (CK) according to the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and the growth inhibition test. Treatment with SK and NK induced apoptosis, as determined by 4,6-diamidino-2-phenylindole staining, and resulted in the up-regulation of Bax expression and down-regulation of Bcl-2, cIAP-1, cellular inhibitor of apoptosis-2, cyclooxygenase-2, inhibitory nitric oxide synthase, and nuclear factor kappaB (NF-kappaB) expressions when compared to CK. The antiproliferative and anti-apoptotic effects appeared to be more pronounced in the cells treated with NK. The antiproliferative effects of the chitosan-added kimchi appeared to be associated with the induction of apoptosis through NF-kappaB or an NF-kappaB-dependent pathway. These results suggest that chitosan has potential to be a valuable active ingredient in functional kimchi products with anticancer effects.

  9. Physical activity counteracts tumor cell growth in colon carcinoma C26-injected muscles: an interim report

    Directory of Open Access Journals (Sweden)

    Charlotte Hiroux

    2016-06-01

    Full Text Available Skeletal muscle tissue is a rare site of tumor metastasis but is the main target of the degenerative processes occurring in cancer-associated cachexia syndrome. Beneficial effects of physical activity in counteracting cancer-related muscle wasting have been described in the last decades. Recently it has been shown that, in tumor xeno-transplanted mouse models, physical activity is able to directly affect tumor growth by modulating inflammatory responses in the tumor mass microenvironment. Here, we investigated the effect of physical activity on tumor cell growth in colon carcinoma C26 cells injected tibialis anterior muscles of BALB/c mice. Histological analyses revealed that 4 days of voluntary wheel running significantly counteracts tumor cell growth in C26-injected muscles compared to the non-injected sedentary controls. Since striated skeletal muscle tissue is the site of voluntary contraction, our results confirm that physical activity can also directly counteract tumor cell growth in a metabolically active tissue that is usually not a target for metastasis.

  10. Resveratrol Modulates the Topoisomerase Inhibitory Potential of Doxorubicin in Human Colon Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Anika Schroeter

    2014-12-01

    Full Text Available Resveratrol (RSV is currently being widely discussed as potentially useful for anticancer therapy in combination with classical chemotherapeutics, e.g., the topoisomerase II (TOP II poison doxorubicin (DOX. However, there is still a lack of knowledge of possible interference at the target enzyme, especially since RSV itself has recently been described to act as a TOP poison. We therefore sought to address the question whether RSV affects DOX-induced genotoxic and cytotoxic effects with special emphasis on TOP II in HT-29 colon carcinoma cells. RSV was found to counteract DOX-induced formation of DNA-TOP-intermediates at ≥100 µM for TOP IIα and at 250 µM for TOP IIβ. As a consequence, RSV modulated the DNA-strand breaking potential of DOX by mediating protective effects with an apparent maximum at 100 µM. At higher concentration ranges (≥200 µM RSV diminished the intracellular concentrations of DOX. Nevertheless, the presence of RSV slightly enhanced the cytotoxic effects of DOX after 1.5 h and 24 h of incubation. Taken together, at least in cell culture RSV was found to affect the TOP-poisoning potential of DOX and to modulate its cytotoxic effectiveness. Thus, further studies are needed to clarify the impact of RSV on the therapeutic effectiveness of DOX under in vivo conditions.

  11. Superior Vena Cava Syndrome and Colon Carcinoma: A Report of a Multifactorial Association

    Directory of Open Access Journals (Sweden)

    Joana Espírito Santo

    2015-01-01

    Full Text Available Introduction. Superior vena cava (SVC syndrome results from the obstruction of blood flow through the SVC, having distinct pathophysiological underlying mechanisms. Cancer is associated with an increased risk of thromboembolism that varies according to patient-, tumor-, and treatment-related factors. An individualized clinical approach is important to pursue the accurate diagnosis of the underlying pathology causing thromboembolism in cancer patients. Case Presentation. The authors present a case of a 58-year-old male with an infrequent presentation of an unknown colon carcinoma, who has never had any symptom until he was hospitalized with the diagnosis of superior vena cava syndrome and pulmonary thromboembolism. The patient had an advanced disease by the time of diagnosis and molecular alterations contributing to abnormal hemostasis. He presented venous and arterial thromboembolism and developed disseminated intravascular coagulopathy after surgery, anticoagulant and transfusion therapy, dying 40 days after the hospitalization. Conclusion. The authors discuss thromboembolic disease and tumor metastasis roles in a cancer patient with SVC syndrome. Thromboembolism in a malignancy context is a challenging clinical entity. A multifactorial perspective of the thrombotic disease is warranted to approach thromboembolism risk and stratify patients suitable to receive adequate anticoagulant prophylaxis and targeted therapies, aiming to improve clinical prognosis.

  12. Metabolic effects of novel N-1-sulfonylpyrimidine derivatives on human colon carcinoma cells.

    Science.gov (United States)

    Glavas-Obrovac, Ljubica; Karner, Ivan; Stefanić, Mario; Kasnar-Samprec, Jelena; Zinić, Biserka

    2005-01-01

    Novel N-1-sulfonylpyrimidine derivatives have a strong antiproliferative activity and an ability to induce apoptosis in treated tumor cells. The purpose of this study was to elucidate the effects of two N-1-sulfonylpyrimidine nucleobases on catalytic activity of tumor cells' enzymes involved in DNA and RNA synthesis, and in de novo and salvage pyrimidine and purine syntheses. Investigations were performed in vitro on colon carcinoma cells (Caco2). The biosynthetic activity of the tumor cells' enzymes was determined using sensitive radio-assays. Enzyme activity in treated cells was calculated relative to untreated control cells. Both of the investigated compounds, 1-(p-toluenesulfonyl) cytosine (TsC) and 5-bromo-1-(methanesulfonyl) uracil (BMsU) inhibited activities of specific enzymes involved in nucleic acid synthesis. BMsU strongly inhibited activities of DNA polymerase alpha (53%), thymidine kinase (68%), thymidilate synthase (43%), and ribonucleotide reductase (46%). De novo biosynthesis of pyrimidine and purine was reduced by 20%. TsC was able to inhibit RNA polymerase (37%), orotate phosphoribosyltransferase (39%), uridine kinase (44%), ribonucleotid reductase (47%), and de novo purine synthesis (61%). Antitumor activity of 1-(p-toluenesulfonyl) cytosine (TsC) and 5-bromo-1-(methanesulfonyl) uracil (BMsU) is closely associated with their inhibitory activity on enzymes that play an important role in the metabolism of tumor cells.

  13. ADAM17 silencing in mouse colon carcinoma cells: the effect on tumoricidal cytokines and angiogenesis.

    Directory of Open Access Journals (Sweden)

    Sudipta Das

    Full Text Available ADAM17 (a disintegrin and metalloprotease 17 is a major sheddase for numerous growth factors, cytokines, receptors, and cell adhesion molecules and is often overexpressed in malignant cells. It is generally accepted that ADAM17 promotes tumor development via activating growth factors from the EGF family, thus facilitating autocrine stimulation of tumor cell proliferation and migration. Here we show, using MC38CEA murine colon carcinoma model, that ADAM17 also regulates tumor angiogenesis and cytokine profile. When ADAM17 was silenced in MC38CEA cells, in vivo tumor growth and in vitro cell motility were significantly diminished, but no effect was seen on in vitro cell proliferation. ADAM17-silencing was accompanied by decreased in vitro expression of vascular endothelial growth factor-A and matrix metalloprotease-9, which was consistent with the limited angiogenesis and slower growth seen in ADAM17-silenced tumors. Among the growth factors susceptible to shedding by ADAM17, neuregulin-1 was the only candidate to mediate the effects of ADAM17 on MC38CEA motility and tumor angiogenesis. Concentrations of TNF and IFNγ, cytokines that synergistically induced proapoptotic effects on MC38CEA cells, were significantly elevated in the lysates of ADAM17-silenced tumors compared to mock transfected controls, suggesting a possible role for ADAM17 in host immune suppression. These results introduce new, complex roles of ADAM17 in tumor progression, including its impact on the anti-tumor immune response.

  14. ADAM17 silencing in mouse colon carcinoma cells: the effect on tumoricidal cytokines and angiogenesis.

    Science.gov (United States)

    Das, Sudipta; Czarnek, Maria; Bzowska, Monika; Mężyk-Kopeć, Renata; Stalińska, Krystyna; Wyroba, Barbara; Sroka, Jolanta; Jucha, Jarosław; Deneka, Dawid; Stokłosa, Paulina; Ogonek, Justyna; Swartz, Melody A; Madeja, Zbigniew; Bereta, Joanna

    2012-01-01

    ADAM17 (a disintegrin and metalloprotease 17) is a major sheddase for numerous growth factors, cytokines, receptors, and cell adhesion molecules and is often overexpressed in malignant cells. It is generally accepted that ADAM17 promotes tumor development via activating growth factors from the EGF family, thus facilitating autocrine stimulation of tumor cell proliferation and migration. Here we show, using MC38CEA murine colon carcinoma model, that ADAM17 also regulates tumor angiogenesis and cytokine profile. When ADAM17 was silenced in MC38CEA cells, in vivo tumor growth and in vitro cell motility were significantly diminished, but no effect was seen on in vitro cell proliferation. ADAM17-silencing was accompanied by decreased in vitro expression of vascular endothelial growth factor-A and matrix metalloprotease-9, which was consistent with the limited angiogenesis and slower growth seen in ADAM17-silenced tumors. Among the growth factors susceptible to shedding by ADAM17, neuregulin-1 was the only candidate to mediate the effects of ADAM17 on MC38CEA motility and tumor angiogenesis. Concentrations of TNF and IFNγ, cytokines that synergistically induced proapoptotic effects on MC38CEA cells, were significantly elevated in the lysates of ADAM17-silenced tumors compared to mock transfected controls, suggesting a possible role for ADAM17 in host immune suppression. These results introduce new, complex roles of ADAM17 in tumor progression, including its impact on the anti-tumor immune response.

  15. Acetaldehyde production and microbial colonization in oral squamous cell carcinoma and oral lichenoid disease.

    Science.gov (United States)

    Marttila, Emilia; Uittamo, Johanna; Rusanen, Peter; Lindqvist, Christian; Salaspuro, Mikko; Rautemaa, Riina

    2013-07-01

    The main aim of this prospective study was to explore the ability of the oral microbiome to produce acetaldehyde in ethanol incubation. A total of 90 patients [30 oral squamous cell carcinoma (OSCC); 30 oral lichenoid disease (OLD); 30 healthy controls (CO)] were enrolled in the study. Microbial samples were taken from the mucosa using a filter paper method. The density of microbial colonization was calculated and the spectrum analyzed. Microbial acetaldehyde production was measured by gas chromatography. The majority (68%) of cultures produced carcinogenic levels of acetaldehyde (>100 μM) when incubated with ethanol (22 mM). The mean acetaldehyde production by microbes cultured from smoker samples was significantly higher (213 μM) than from non-smoker samples (141 μM) (P=.0326). The oral microbiota from OSCC, OLD patients and healthy individuals are able to produce carcinogenic levels of acetaldehyde. The present provisional study suggests smoking may increase the production of acetaldehyde. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Clotrimazole decreases glycolysis and the viability of lung carcinoma and colon adenocarcinoma cells.

    Science.gov (United States)

    Penso, Julia; Beitner, Rivka

    2002-09-20

    Glycolysis is known to be the primary energy source in most cancer cells. We investigated here the effect of clotrimazole (1-(alpha-2-chlorotrityl)imidazole), the antifungal azole derivative, which was recently recognized as calmodulin antagonist, on the levels of glucose 1,6-bisphosphate and fructose 1,6-bisphosphate, the two stimulatory signal molecules of glycolysis, and on ATP content and cell viability in LL/2 Lewis lung carcinoma cells and CT-26 colon adenocarcinoma cells. We found that clotrimazole induced a significant, dose- and time-dependent reduction in the levels of glucose 1,6-bisphosphate, fructose 1,6-bisphosphate, ATP, and cell viability. These findings suggest that clotrimazole causes a reduction in glycolysis and ATP levels, which eventually leads to cell destruction after 3 h of treatment. Since cell proliferation was also reported to be inhibited by calmodulin antagonists, this substance is most promising agent in treatment of cancer by inhibiting both cell proliferation and the glycolytic supply of ATP required for cancer cell growth. Copyright 2002 Elsevier Science B.V.

  17. Euphorbia Species-derived Diterpenes and Coumarins as Multidrug Resistance Modulators in Human Colon Carcinoma Cells.

    Science.gov (United States)

    Wiśniewski, Jerzy; Wesołowska, Olga; Środa-Pomianek, Kamila; Paprocka, Maria; Bielawska-Pohl, Aleksandra; Krawczenko, Agnieszka; Duarte, Noelia; Ferreira, Maria-José U; Duś, Danuta; Michalak, Krystyna

    2016-05-01

    Recently, many new potent multidrug resistance (MDR) reversal agents have been discovered, among them lathyrane and jatrophane diterpenes isolated from various Euphorbia species. In the present study, the cytotoxicity, P-glycoprotein inhibition activity, and MDR reversal potency of six diterpenes and two coumarins from two Euphorbia species were studied in human colon carcinoma LoVo cells, and doxorubicin-resistant, LoVo/Dx cells. Cytotoxicity of the studied compounds (alone and in combination with doxorubicin) was investigated. Inhibition of P-glycoprotein transport activity was monitored by flow cytometry. Changes in intracellular doxorubicin accumulation were observed by means of fluorescence microscopy. Latilagascene B was demonstrated to be an effective P-glycoprotein inhibitor, able to increase doxorubicin accumulation in resistant cells, however not able to restore doxorubicin cytotoxicity in LoVo/Dx cells. The structure of latilagascene B seems to be an interesting candidate for further synthesis of new derivatives of reduced cytotoxicity and high anti-MDR potency. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  18. Breast metastasis of primary colon cancer Metástasis en mama de carcinoma primario de colon

    Directory of Open Access Journals (Sweden)

    L. Fernández de Bobadilla

    2004-06-01

    Full Text Available Metastatic tumors to the breast from colon adenocarcinoma are very rare. They are usually indicative of disseminated disease, and the prognosis is poor. Generally, radical operation should be avoided unless needed for palliation. This case report described a patient with breast metastasis from colon adenocarcinoma treated by simple mastectomy.La metástasis en la mama de tumores de colon es una entidad muy poco frecuente. El pronóstico a largo plazo es infausto, pues esta lesión es expresión de enfermedad sistémica. El tratamiento quirúrgico debe ser lo más conservador posible, ya que es un tratamiento paliativo. Presentamos un caso de esta rara entidad, tratada mediante mastectomía.

  19. MSH3 mismatch repair protein regulates sensitivity to cytotoxic drugs and a histone deacetylase inhibitor in human colon carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Jae Myung Park

    Full Text Available MSH3 is a DNA mismatch repair (MMR gene that undergoes frequent somatic mutation in colorectal cancers (CRCs with MMR deficiency. MSH3, together with MSH2, forms the MutSβ heteroduplex that interacts with interstrand cross-links induced by drugs such as cisplatin. To date, the impact of MSH3 on chemosensitivity is unknown.We utilized isogenic HCT116 (MLH1-/MSH3- cells where MLH1 is restored by transfer of chromosome 3 (HCT116+ch3 and also MSH3 by chromosome 5 (HCT116+3+5. We generated HCT116+3+5, SW480 (MLH1+/MSH3+ and SW48 (MLH1-/MSH3+ cells with shRNA knockdown of MSH3. Cells were treated with 5-fluorouracil (5-FU, SN-38, oxaliplatin, or the histone deacetylase (HDAC inhibitor PCI-24781 and cell viability, clonogenic survival, DNA damage and apoptosis were analyzed.MSH3-deficient vs proficient CRC cells showed increased sensitivity to the irinotecan metabolite SN-38 and to oxaliplatin, but not 5-FU, as shown in assays for apoptosis and clonogenic survival. In contrast, suppression of MLH1 attenuated the cytotoxic effect of 5-FU, but did not alter sensitivity to SN-38 or oxaliplatin. The impact of MSH3 knockdown on chemosensitivity to SN-38 and oxaliplatin was maintained independent of MLH1 status. In MSH3-deficient vs proficient cells, SN-38 and oxaliplatin induced higher levels of phosphorylated histone H2AX and Chk2, and similar results were found in MLH1-proficient SW480 cells. MSH3-deficient vs proficient cells showed increased 53BP1 nuclear foci after irradiation, suggesting that MSH3 can regulate DNA double strand break (DSB repair. We then utilized PCI-24781 that interferes with homologous recombination (HR indicated by a reduction in Rad51 expression. The addition of PCI-24781 to oxaliplatin enhanced cytotoxicity to a greater extent compared to either drug alone.MSH3 status can regulate the DNA damage response and extent of apoptosis induced by chemotherapy. The ability of MSH3 to regulate chemosensitivity was independent of MLH1

  20. Mucinous carcinoma of the colon in a 16-year-old Turkish boy with Bloom syndrome: cytogenetic, histopathologic, TP53 gene and protein expression studies.

    Science.gov (United States)

    Balci, S; Aktas, D

    1999-05-01

    A 17-year-old Turkish boy with Bloom syndrome (BS) developed mucinous carcinoma of the transverse colon. He was followed from 2 to 17 years of age. Increased sister chromatid exchanges (SCE) were observed, and he was diagnosed with BS at the age of 7. Sun-sensitive skin lesions were examined by skin biopsy, and histopathological studies of these lesions were done. During the follow-up period, an intraabdominal mass at the transverse colon was found, and mucinous carcinoma of colon was diagnosed at the age of 16. We examined TP53 protein expression from paraffin-embedded colon tissue of the patient with an immunohistochemical method. Polymerase chain reaction products of exons 4-9 of the TP53 gene were examined by SSCP. No evidence of overexpression of TP53 protein or mutations of the TP53 gene was observed. The patient in this report is the first case with a mucinous carcinoma of colon diagnosed at an early age in the Bloom Syndrome Registry. Based on our results, carcinoma of the colon in BS patient may occur earlier than 35 years of age and the TP53 gene may not be directly related to carcinoma in Bloom syndrome.

  1. Comparison of laparoscopic peritoneal vaginoplasty and sigmoid colon vaginoplasty performed during radical surgery for primary vaginal carcinoma.

    Science.gov (United States)

    Yao, Fengqiu; Zhao, Weidong; Chen, Gang; Zhang, Aijun; Sun, Fanglin; Hu, Weiping; Ling, Bin

    2014-09-30

    Radical surgery of primary vaginal carcinoma typically involves partial or complete resection of the vagina, and young patients in particular can experience sexual dysfunction after surgery. Vaginoplasty is mandatory for this population, multiple vaginal reconstructive techniques have been reported. Here we attempted to determine whether the peritoneum is a feasible alternative to the sigmoid colon in vaginoplasty performed during radical surgery. Between February 2005 and July 2009, 12 patients underwent radical surgery for Federation of International Gynecology and Obstetrics Stage I primary vaginal carcinoma in the upper one-third of the vagina. To retain a sex life, the patients received vaginoplasty either with the peritoneum (peritoneal group, 5 patients) or with the sigmoid colon (sigmoid group, 7 patients) during radical surgery. Surgeries were performed at the Anhui Provincial Hospital in China. The data between the two groups was retrospectively analyzed. The operating time was shorter for the peritoneal group than for the sigmoid group (Pvaginas between the two groups during surgery (P>0.05). No metastasis or operation-related complications were observed in any of the patients. Six months after surgery, the neo-vaginas of both groups were smooth, soft, and moist. The neo-vaginas in the sigmoid group were similar in size during and 6 months after surgery. The neo-vaginas in the peritoneal group were shorter (although no less wide) 6 months after surgery (Pvaginas of the peritoneal group, and intestinalization in the neo-vaginas of the sigmoid group. At the 36-month follow-up, all patients were clinically free of disease. Laparoscopic vaginoplasty using the peritoneum compared with using the sigmoid colon is simpler and more feasible for management of Stage I primary vaginal carcinoma. Its benefits include shorter operating time, no bowel disturbance, and production of a hygienic vaginal environment, as well as a potential sex life and oncologic outcome

  2. Salicylic acid induces apoptosis in colon carcinoma cells grown in-vitro: Influence of oxygen and salicylic acid concentration

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    Zitta, Karina; Meybohm, Patrick; Bein, Berthold; Huang, Ying; Heinrich, Christin; Scholz, Jens; Steinfath, Markus; Albrecht, Martin, E-mail: Albrecht@anaesthesie.uni-kiel.de

    2012-04-15

    In solid tumors the hypoxic environment can promote tumor progression and resistance to therapy. Recently, acetylsalicylic acid a major component of analgesic drugs and its metabolite salicylic acid (SA) have been shown to reduce the risk of colon cancer, but the mechanisms of action remain still unclear. Here we elucidate the effects of physiologically relevant concentrations of SA on colon carcinoma cells (CaCo-2) grown under normoxic and hypoxic conditions. Western blotting, caspase-3/7 apoptosis assays, MTS cell-proliferation assays, LDH cytotoxicity assays and hydrogen peroxide measurements were performed to investigate the effects of 1 and 10 {mu}M SA on CaCo-2 cells grown under normoxic conditions and cells exposed to hypoxia. Under normoxic conditions, SA did not influence cell proliferation or LDH release of CaCo-2 cells. However, caspase-3/7 activity was significantly increased. Under hypoxia, cell proliferation was reduced and LDH release and caspase-3/7 activities were increased. None of these parameters was altered by the addition of SA under hypoxic conditions. Hypoxia increased hydrogen peroxide concentrations 300-fold and SA significantly augmented the release of hydrogen peroxide under normoxic, but not under hypoxic conditions. Phosphorylation of the pro-survival kinases akt and erk1/2 was not changed by SA under hypoxic conditions, whereas under normoxia SA reduced phosphorylation of erk1/2 after 2 hours. We conclude that in colon carcinoma cells effects of SA on apoptosis and cellular signaling are dependent on the availability of oxygen. -- Highlights: Black-Right-Pointing-Pointer Effects of salicylic acid on colon carcinoma cells grown under normoxic and hypoxic conditions Black-Right-Pointing-Pointer Salicylic acid increases caspase-3/7 activity and hydrogen peroxide release under normoxia Black-Right-Pointing-Pointer Salicylic acid decreases pro-survival erk-1/2 phosphorylation under normoxia Black-Right-Pointing-Pointer Salicylic acid does

  3. Gut microbial diversity in health and disease: experience of healthy Indian subjects, and colon carcinoma and inflammatory bowel disease patients.

    Science.gov (United States)

    Bamola, V Deepak; Ghosh, Arnab; Kapardar, Raj Kishor; Lal, Banwari; Cheema, Simrita; Sarma, Priyangshu; Chaudhry, Rama

    2017-01-01

    Background: The intestinal microbiota, through complex interactions with the gut mucosa, play a key role in the pathogenesis of colon carcinoma and inflammatory bowel disease (IBD). The disease condition and dietary habits both influence gut microbial diversity. Objective: The aim of this study was to assess the gut microbial profile of healthy subjects and patients with colon carcinoma and IBD. Healthy subjects included 'Indian vegetarians/lactovegetarians', who eat plant produce, milk and milk products, and 'Indian non-vegetarians', who eat plant produce, milk and milk products, certain meats and fish, and the eggs of certain birds and fish. 'Indian vegetarians' are different from 'vegans', who do not eat any foods derived wholly or partly from animals, including milk products. Design: Stool samples were collected from healthy Indian vegetarians/lactovegetarians and non-vegetarians, and colon cancer and IBD patients. Clonal libraries of 16S ribosomal DNA (rDNA) of bacteria were created from each sample. Clones were sequenced from one representative sample of each group. Approximately 500 white colonies were picked at random from each sample and 100 colonies were sequenced after amplified rDNA restriction analysis. Results: The dominant phylum from the healthy vegetarian was Firmicutes (34%), followed by Bacteroidetes (15%). The balance was reversed in the healthy non-vegetarian (Bacteroidetes 84%, Firmicutes 4%; ratio 21:1). The colon cancer and IBD patients had higher percentages of Bacteroidetes (55% in both) than Firmicutes (26% and 12%, respectively) but lower Bacteroidetes:Firmicutes ratios (3.8:1 and 2.4:1, respectively) than the healthy non-vegetarian. Bacterial phyla of Verrucomicrobiota and Actinobacteria were detected in 23% and 5% of IBD and colon patients, respectively. Conclusions: Ribosomal Database Project profiling of gut flora in this study population showed remarkable differences, with unique diversity attributed to different diets and disease

  4. Antiproliferative Effects of Tetrabuthylammonium Chloride Ionic Liquid on HCT 8 Human Colon Carcinoma Cells

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    Gabi Dumitrescu

    2017-05-01

    Full Text Available The ionic liquids have attracted a great of attention in the scientific community due to their potential pharmaceutical such as antimicrobial. In this paper, the main objective was the assessment of the cytotoxic effect of tetrabutylammonium chloride against HCT 8 human colon carcinoma cell line. The cells were cultured in 75 cm2 culture flasks  using RPMI medium supplemented with 10% inactivated fetal bovine serum (FBS, penicillin (100 IU/mL and streptomycin (100 μg/mL and maintained at 37 °C and 5% CO2. Before achieving viability test, the cells were harvested using trypsin solution (0.25%. Then, the cells were seeded in 24 – well plates at a density of 5 x 105 cells/mL in 100 µL medium/well in order to reach confluence. After 24 h, the medium was replaced with fresh medium containing different concentrations of ionic liquid, respectively, 0.085, 0.17, 0.34, 0.68 and 1.36 mg /mL. Control group contained cells without treatment. Cell proliferation kinetics have been studied at 24 and 48 h after IL treatment, following trypsinization and counting total cells per plate by using a Trypan blue dye and a hemocytometer. Data obtained from the growth kinetics assay shows that the tetrabutylammonium chloride (TBAC had an inhibitory effect on the growth of cells in a concentration dependent manner. The maximum inhibitory effect on HCT 8 cells it was obtained at 1.36 mg TBAC/mL.

  5. Magnetic Nanoparticles from Magnetospirillum gryphiswaldense Increase the Efficacy of Thermotherapy in a Model of Colon Carcinoma

    Science.gov (United States)

    Mannucci, Silvia; Ghin, Leonardo; Conti, Giamaica; Tambalo, Stefano; Lascialfari, Alessandro; Orlando, Tomas; Benati, Donatella; Bernardi, Paolo; Betterle, Nico; Bassi, Roberto; Marzola, Pasquina; Sbarbati, Andrea

    2014-01-01

    Magnetic nanoparticles (MNPs) are capable of generate heating power under the influence of alternating magnetic fields (AMF); this behaviour recently opened new scenarios for advanced biomedical applications, mainly as new promising tumor therapies. In this paper we have tested magnetic nanoparticles called magnetosomes (MNs): a class of MNPs naturally produced by magnetotactic bacteria. We extracted MNs from Magnetospirillum gryphiswaldense strain MSR-1 and tested the interaction with cellular elements and anti-neoplastic activity both in vitro and in vivo, with the aim of developing new therapeutic approaches for neoplastic diseases. In vitro experiments performed on Human Colon Carcinoma HT-29 cell cultures demonstrated a strong uptake of MNs with no evident signs of cytotoxicity and revealed three phases in the interaction: adherence, transport and accumulation in Golgi vesicles. In vivo studies were performed on subcutaneous tumors in mice; in this model MNs are administered by direct injection in the tumor volume, then a protocol consisting of three exposures to an AMF rated at 187 kHz and 23kA/m is carried out on alternate days, over a week. Tumors were monitored by Magnetic Resonance Imaging (MRI) to obtain information about MNs distribution and possible tissue modifications induced by hyperthermia. Histological analysis showed fibrous and necrotic areas close to MNs injection sites in mice subjected to a complete thermotherapy protocol. These results, although concerning a specific tumor model, could be useful to further investigate the feasibility and efficacy of protocols based on MFH. Magnetic nanoparticles naturally produced and extracted from bacteria seem to be promising candidates for theranostic applications in cancer therapy. PMID:25289664

  6. Magnetic nanoparticles from Magnetospirillum gryphiswaldense increase the efficacy of thermotherapy in a model of colon carcinoma.

    Directory of Open Access Journals (Sweden)

    Silvia Mannucci

    Full Text Available Magnetic nanoparticles (MNPs are capable of generate heating power under the influence of alternating magnetic fields (AMF; this behaviour recently opened new scenarios for advanced biomedical applications, mainly as new promising tumor therapies. In this paper we have tested magnetic nanoparticles called magnetosomes (MNs: a class of MNPs naturally produced by magnetotactic bacteria. We extracted MNs from Magnetospirillum gryphiswaldense strain MSR-1 and tested the interaction with cellular elements and anti-neoplastic activity both in vitro and in vivo, with the aim of developing new therapeutic approaches for neoplastic diseases. In vitro experiments performed on Human Colon Carcinoma HT-29 cell cultures demonstrated a strong uptake of MNs with no evident signs of cytotoxicity and revealed three phases in the interaction: adherence, transport and accumulation in Golgi vesicles. In vivo studies were performed on subcutaneous tumors in mice; in this model MNs are administered by direct injection in the tumor volume, then a protocol consisting of three exposures to an AMF rated at 187 kHz and 23kA/m is carried out on alternate days, over a week. Tumors were monitored by Magnetic Resonance Imaging (MRI to obtain information about MNs distribution and possible tissue modifications induced by hyperthermia. Histological analysis showed fibrous and necrotic areas close to MNs injection sites in mice subjected to a complete thermotherapy protocol. These results, although concerning a specific tumor model, could be useful to further investigate the feasibility and efficacy of protocols based on MFH. Magnetic nanoparticles naturally produced and extracted from bacteria seem to be promising candidates for theranostic applications in cancer therapy.

  7. Plaque assay for human coronavirus NL63 using human colon carcinoma cells

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    Drosten Christian

    2008-11-01

    Full Text Available Abstract Background Coronaviruses cause a broad range of diseases in animals and humans. Human coronavirus (hCoV NL63 is associated with up to 10% of common colds. Viral plaque assays enable the characterization of virus infectivity and allow for purifying virus stock solutions. They are essential for drug screening. Hitherto used cell cultures for hCoV-NL63 show low levels of virus replication and weak and diffuse cytopathogenic effects. It has not yet been possible to establish practicable plaque assays for this important human pathogen. Results 12 different cell cultures were tested for susceptibility to hCoV-NL63 infection. Human colon carcinoma cells (CaCo-2 replicated virus more than 100 fold more efficiently than commonly used African green monkey kidney cells (LLC-MK2. CaCo-2 cells showed cytopathogenic effects 4 days post infection. Avicel, agarose and carboxymethyl-cellulose overlays proved suitable for plaque assays. Best results were achieved with Avicel, which produced large and clear plaques from the 4th day of infection. The utility of plaque assays with agrose overlay was demonstrated for purifying virus, thereby increasing viral infectivity by 1 log 10 PFU/mL. Conclusion CaCo-2 cells support hCoV-NL63 better than LLC-MK2 cells and enable cytopathogenic plaque assays. Avicel overlay is favourable for plaque quantification, and agarose overlay is preferred for plaque purification. HCoV-NL63 virus stock of increased infectivity will be beneficial in antiviral screening, animal modelling of disease, and other experimental tasks.

  8. Activation by zinc of the human gastrin gene promoter in colon cancer cells in vitro and in vivo.

    Science.gov (United States)

    Marshall, Kathryn M; Laval, Marie; Estacio, Ortis; Hudson, Damien F; Kalitsis, Paul; Shulkes, Arthur; Baldwin, Graham S; Patel, Oneel

    2015-10-01

    Over-expression of growth factors can contribute to the development and progression of cancer, and gastrins in particular have been implicated in accelerating the development of gastrointestinal cancers. Previously our group showed that hypoxia, cobalt chloride (a hypoxia mimetic) and zinc chloride could activate the expression of the gastrin gene in vitro. To characterise activation of the gastrin promoter by zinc ions further in vivo, TALEN technology was used to engineer a luciferase reporter construct into the endogenous human gastrin gene promoter in SW480 colon cancer cells. Gastrin promoter activity in the resultant Gast(luc) SW480 colon cancer cells was then measured by bioluminescence in cell culture and in tumour xenografts in SCID mice. Activation of intracellular signalling pathways was assessed by Western blotting. Activation of the gastrin promoter by zinc ions was concentration dependent in vitro and in vivo. Zinc ions significantly stimulated phosphorylation of ERK1/2 (MAPK pathway) but not of Akt (PI3K pathway). We conclude that the endogenous gastrin promoter is responsive to zinc ions, likely via activation of the MAPK pathway.

  9. Metastatic Infiltrating Ductal Carcinoma of the Breast to the Colon: A Case Report and Literature Review

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    Salih Samo

    2013-01-01

    Full Text Available True metastatic involvement of the colon is rare. Colonic metastases occur most commonly secondary to peritoneal metastases from intra-abdominal malignancies. Breast cancer is the most common malignancy that metastasizes hematogenously to the colon. Colonic metastatic disease mimics primary colonic tumors in its presentation. Colonic metastatic involvement is a poor prognostic sign, and the pathologist should be informed about the history of the primary breast cancer when examining the pathologic specimens. In this paper, we report a case of an ileocecal mass found to be histologically consistent with metastatic ductal breast cancer, and then we review the literature about breast cancer metastases to the gastrointestinal tract in general and colon in particular.

  10. Anti-tumor effects of fibroblast growth factor-binding protein (FGF-BP knockdown in colon carcinoma

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    Schulze Daniel

    2011-11-01

    Full Text Available Abstract Background Fibroblast growth factors FGF-1 and FGF-2 are often upregulated in tumors, but tightly bound to heparan sulphate proteoglycans of the extracellular matrix (ECM. One mechanism of their bioactivation relies on the FGF-binding protein (FGF-BP which, upon reversible binding to FGF-1 or -2, leads to their release from the ECM. FGF-BP increases tumorigenicity and is highly expressed in tumors like colon carcinoma. In this paper, we analyse cellular and molecular consequences of RNAi-mediated FGF-BP knockdown in colon carcinoma, and explore the therapeutic effects of the nanoparticle-mediated delivery of small interfering RNAs (siRNAs for FGF-BP targeting. Results Employing stable RNAi cells, we establish a dose-dependence of cell proliferation on FGF-BP expression levels. Decreased proliferation is mirrored by alterations in cell cycle distribution and upregulation of p21, which is relevant for mediating FGF-BP effects. While inhibition of proliferation is mainly associated with reduced Akt and increased GSK3β activation, antibody array-based analyses also reveal other alterations in MAPK signalling. Additionally, we demonstrate induction of apoptosis, mediated through caspase-3/7 activation, and alterations in redox status upon FGF-BP knockdown. These effects are based on the upregulation of Bad, Bax and HIF-1α, and the downregulation of catalase. In a therapeutic FGF-BP knockdown approach based on RNAi, we employ polymer-based nanoparticles for the in vivo delivery of siRNAs into established wildtype colon carcinoma xenografts. We show that the systemic treatment of mice leads to the inhibition of tumor growth based on FGF-BP knockdown. Conclusions FGF-BP is integrated in a complex network of cytoprotective effects, and represents a promising therapeutic target for RNAi-based knockdown approaches.

  11. Induction of apoptosis by cannabinoids in prostate and colon cancer cells is phosphatase dependent.

    Science.gov (United States)

    Sreevalsan, Sandeep; Joseph, Sonia; Jutooru, Indira; Chadalapaka, Gayathri; Safe, Stephen H

    2011-11-01

    We hypothesized that the anticancer activity of cannabinoids was linked to induction of phosphatases. The effects of cannabidiol (CBD) and the synthetic cannabinoid WIN-55,212 (WIN) on LNCaP (prostate) and SW480 (colon) cancer cell proliferation were determined by cell counting; apoptosis was determined by cleavage of poly(ADP)ribose polymerase (PARP) and caspase-3 (Western blots); and phosphatase mRNAs were determined by real-time PCR. The role of phosphatases and cannabinoid receptors in mediating CBD- and WIN-induced apoptosis was determined by inhibition and receptor knockdown. CBD and WIN inhibited LNCaP and SW480 cell growth and induced mRNA expression of several phosphatases, and the phosphatase inhibitor sodium orthovanadate significantly inhibited cannabinoid-induced PARP cleavage in both cell lines, whereas only CBD-induced apoptosis was CB1 and CB2 receptor-dependent. Cannabinoid receptor agonists induce phosphatases and phosphatase-dependent apoptosis in cancer cell lines; however, the role of the CB receptor in mediating this response is ligand-dependent.

  12. Fibromodulin deficiency reduces collagen structural network but not glycosaminoglycan content in a syngeneic model of colon carcinoma.

    Science.gov (United States)

    Olsson, P Olof; Kalamajski, Sebastian; Maccarana, Marco; Oldberg, Åke; Rubin, Kristofer

    2017-01-01

    Tumor barrier function in carcinoma represents a major challenge to treatment and is therefore an attractive target for increasing drug delivery. Variables related to tumor barrier include aberrant blood vessels, high interstitial fluid pressure, and the composition and structure of the extracellular matrix. One of the proteins associated with dense extracellular matrices is fibromodulin, a collagen fibrillogenesis modulator expressed in tumor stroma but scarce in normal loose connective tissues. Here, we investigated the effects of fibromodulin on stroma ECM in a syngeneic murine colon carcinoma model. We show that fibromodulin deficiency decreased collagen fibril thickness but glycosaminoglycan content and composition were unchanged. Furthermore, vascular density, pericyte coverage and macrophage amount were unaffected. Fibromodulin can therefore be a unique effector of dense collagen matrix assembly in tumor stroma and, without affecting other major matrix components or the cellular composition, can function as a main agent in tumor barrier function.

  13. Adjuvant postoperative radiation therapy for colorectal carcinoma above the peritoneal reflection. II. Antimesenteric wall ascending and descending colon and cecum

    Energy Technology Data Exchange (ETDEWEB)

    Kopelson, G.

    1983-08-15

    From 1970 to 1981, 50 patients had curative surgery for carcinoma of the cecum, ascending, or descending colon and were Stage greater than or equal to B2. In 15 cases, the lesion originated on the antimesenteric (posterolateral) bowel wall. Of seven cases (with minimum three-year follow-up) not receiving adjuvant postoperative regional irradiation, four recurred in the tumor bed/abdominal wall versus 0/3 irradiated patients. Similarly, the five-year survival was improved in the irradiated group (2/3) versus only 2/9 in the unirradiated group. Patients with transmural extension of right or left colon cancers originating on the anti mesenteric (posterolateral) bowel wall may have a high incidence of postoperative regional failure which may be decreased by adjuvant postoperative regional irradiation.

  14. How can we treat a patient with liver cirrhosis (hepatitis C virus), hepatocellular carcinoma, and synchronous colon cancer?

    Science.gov (United States)

    Antoniou, E; Mantas, D; Paraskeva, P; Dimitroulis, D; Smyrnis, A; Nikitakis, N; Labadariou, A; Tsavaris, N; Vernicos, P; Kostakis, A

    2012-11-01

    The coexistence of liver cirrhosis with hepatocellular carcinoma (HCC) and colon cancer (Ca), which is a rare clinical condition, was treated in a liver transplant recipient. A 46-year-old man, diagnosed incidentally during an ultrasound (US) examination with a 3.5-cm HCC in segment VII related to chronic hepatitis C virus (HCV), was referred for liver resection. He underwent a laparoscopic protocol evaluation for liver cirrhosis. Liver appearance and biopsy of the left lobe showed Child B/C liver cirrhosis. Because he fulfilled the Milan criteria, we suggested an orthotopic liver transplantation (OLT). During protocol colonoscopy, we discovered an ulcerative sigmoid colon Ca. Three weeks after completing the pre-OLT assessment he underwent an OLT and was discharged home on day 9 on an immunosuppressive regimen of Everolimus, Myfortic, and Prezolone. Two months after transplantation, the patient underwent a sigmoidectomy and for nearly 1 month thereafter received chemotherapy for colon Ca (6 cycles of FOLFOX:Folinic Acid+Fluorouracil+Oxaliplatin). One and a half years after OLT, patient was in good condition but presented with an increased alpha fetoprotein (a-FP) without other findings. A couple of months later we discovered a colon Ca recurrence and 3 small liver metastases. Patient underwent a bowel resection with Hartmann's procedure. Almost immediately after the last operation, he was found to suffer multiple myeloma. He underwent chemotherapy for both malignancies with good responses, but a few months later died of severe sepsis. The relevant literature regarding treatment of liver cirrhosis complicated with HCC and synchronous colon Ca reveals poor and controversial outcomes. Our patient underwent chemotherapy immediately after colon resection in the presence of with a good functioning liver. Although his condition was satisfactory after OLT, the optimal treatment of such complicated patients is as yet uncertain. Copyright © 2012 Elsevier Inc. All rights

  15. Lectins from the Red Marine Algal Species Bryothamnion seaforthii and Bryothamnion triquetrum as Tools to Differentiate Human Colon Carcinoma Cells

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    Vicente P. T. Pinto

    2009-01-01

    Full Text Available The carbohydrate-binding activity of the algal lectins from the closely related red marine algal species Bryothamnion triquetrum (BTL and Bryothamnion seaforthii (BSL was used to differentiate human colon carcinoma cell variants with respect to their cell membrane glyco-receptors. These lectins interacted with the cells tested in a dose-dependent manner. Moreover, the fluorescence spectra of both lectins clearly differentiated the cells used as shown by FACS profiles. Furthermore, as observed by confocal microscopy, BTL and BSL bound to cell surface glycoproteins underwent intense internalization, which makes them possible tools in targeting strategies.

  16. Modulation of TRAIL resistance in colon carcinoma cells: Different contributions of DR4 and DR5

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    de Vries Elisabeth GE

    2011-01-01

    Full Text Available Abstract Background rhTRAIL is a therapeutic agent, derived from the TRAIL cytokine, which induces apoptosis in cancer cells by activating the membrane death receptors 4 and 5 (DR4 and DR5. Here, we investigated each receptor's contribution to rhTRAIL sensitivity and rhTRAIL resistance. We assessed whether agonistic DR4 or DR5 antibodies could be used to circumvent rhTRAIL resistance, alone or in combination with various chemotherapies. Methods Our study was performed in an isogenic model comprised of the SW948 human colon carcinoma cell line and its rhTRAIL resistant sub-line SW948-TR. Effects of rhTRAIL and agonistic DR4/DR5 antibodies on cell viability were measured using MTT assays and identification of morphological changes characteristic of apoptosis, after acridine orange staining. Sensitivity to the different death receptor ligands was stimulated using pretreatment with the cytokine IFN-gamma and the proteasome inhibitor MG-132. To investigate the mechanisms underlying the changes in rhTRAIL sensitivity, alterations in expression levels of targets of interest were measured by Western blot analysis. Co-immunoprecipitation was used to determine the composition of the death-inducing signalling complex at the cell membrane. Results SW948 cells were sensitive to all three of the DR-targeting agents tested, although the agonistic DR5 antibody induced only weak caspase 8 cleavage and limited apoptosis. Surprisingly, agonistic DR4 and DR5 antibodies induced equivalent DISC formation and caspase 8 cleavage at the level of their individual receptors, suggesting impairment of further caspase 8 processing upon DR5 stimulation. SW948-TR cells were cross-resistant to all DR-targeting agents as a result of decreased caspase 8 expression levels. Caspase 8 protein expression was restored by MG-132 and IFN-gamma pretreatment, which also re-established sensitivity to rhTRAIL and agonistic DR4 antibody in SW948-TR. Surprisingly, MG-132 but not IFN

  17. Utility of CK7 and CK20 immunohistochemistry in the detection of synchronous breast and colon carcinoma in a pleural effusion: a case report and supporting survey of archival material

    DEFF Research Database (Denmark)

    Stopyra, G A; Warhol, M J; Multhaupt, H A

    2001-01-01

    , respectively. An immunohistochemical survey of archival breast and colon primary and metastatic carcinomas confirmed the established CK7+/CK20- phenotype of breast and CK7-/CK20+ phenotype of colon primary carcinomas, and the maintenance of this phenotype in metastases thereof. A survey of benign and malignant...

  18. Clonal evolution demonstrated by flow cytometric DNA analysis of a human colonic carcinoma grown in nude mice

    DEFF Research Database (Denmark)

    Vindeløv, L L; Spang-Thomsen, M; Visfeldt, J

    1982-01-01

    A spontaneous change in DNA content of a human colonic carcinoma grown in nude mice was observed fortuitously. The tumor initially had a G1 cell DNA content of 1.3 times that of normal cells. Flow cytometric DNA analysis showed in transplant generation 56 the appearance of a new subpopulation whi...... evolution of a tumor would be less pronounced if old subpopulations often become extinct as new ones emerge. Heterogeneity of human tumors is of clinical importance because the individual subpopulations may have different sensitivity patterns to antineoplastic drugs.......A spontaneous change in DNA content of a human colonic carcinoma grown in nude mice was observed fortuitously. The tumor initially had a G1 cell DNA content of 1.3 times that of normal cells. Flow cytometric DNA analysis showed in transplant generation 56 the appearance of a new subpopulation which...... in three passages completely overgrew the original population. The DNA content of the new subpopulation was twice that of the original population. The observation supports the hypothesis of clonal evolution of tumor cell populations. The growth rates of the tumor before and after the change showed...

  19. Curcumin conjugated with PLGA potentiates sustainability, anti-proliferative activity and apoptosis in human colon carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Bhargav N Waghela

    Full Text Available Curcumin, an ingredient of turmeric, exhibits a variety of biological activities such as anti-inflammatory, anti-atherosclerotic, anti-proliferative, anti-oxidant, anti-cancer and anti-metastatic. It is a highly pleiotropic molecule that inhibits cell proliferation and induces apoptosis in cancer cells. Despite its imperative biological activities, chemical instability, photo-instability and poor bioavailability limits its utilization as an effective therapeutic agent. Therefore, enhancing the bioavailability of curcumin may improve its therapeutic index for clinical setting. In the present study, we have conjugated curcumin with a biodegradable polymer Poly (D, L-lactic-co-glycolic acid and evaluated its apoptotic potential in human colon carcinoma cells (HCT 116. The results show that curcumin-PLGA conjugate efficiently inhibits cell proliferation and cell survival in human colon carcinoma cells as compared to native curcumin. Additionally, curcumin conjugated with PLGA shows improved cellular uptake and exhibits controlled release at physiological pH as compared to native curcumin. The curcumin-PLGA conjugate efficiently activates the cascade of caspases and promotes intrinsic apoptotic signaling. Thus, the results suggest that conjugation potentiates the sustainability, anti-proliferative and apoptotic activity of curcumin. This approach could be a promising strategy to improve the therapeutic index of cancer therapy.

  20. Delineating the effect of demethylating agent 5-aza-2'-deoxycytidine on human Caco-2 colonic carcinoma cells.

    Science.gov (United States)

    Li, Xiumei; Qin, Bingzhao; Liu, B O

    2016-07-01

    Aberrant epigenetic changes are known to contribute to various phases of tumor development. The gene function loss caused by aberrant methylation is analogous to genetic mutations. Unlike genetic mutations, epigenetic alterations can be reversed. 5-Aza-2'-deoxycytidine (5-aza-CdR) has been approved by the Food and Drug Administration for the treatment of certain types of cancer, such as MDS and leukemia. The aim of the present study was to determine whether 5-aza-CdR has the potential to be used in the treatment of colon cancer using a human Caco-2 colonic carcinoma cell line. The effect of 5-aza-CdR on cell proliferation, cell cycle, apoptosis and reversal of aberrant methylation of the Ras association domain family 1A (RASSF1A) gene was also examined. The 5-aza-CdR was prepared at different concentrations in sterile tri-distilled water at 0.4, 1.6, 6.4, 25.6 and 102.4 µmol/l and employed to treat the human Caco-2 colonic carcinoma cells. An MTT assay was used to detect the effect of 5-aza-CdR on cell proliferation. Flow cytometry was used to examine the cell cycle and apoptosis. The RASSF1A mRNA transcript level was examined by reverse transcription-polymerase chain reaction. The results showed that 5-aza-CdR inhibited the proliferation of Caco-2 cells in a time- and concentration-dependent manner (pCaco-2 cells. In conclusion, 5-aza-CdR inhibited growth and promoted apoptosis in Caco-2 cells by upregulating the epigenetically silenced tumor suppressor RASSF1A gene.

  1. Thirty-day outcomes in patients treated with en bloc colectomy and pancreatectomy for locally advanced carcinoma of the colon.

    Science.gov (United States)

    Paquette, Ian M; Swenson, Brian R; Kwaan, Mary R; Mellgren, Anders F; Madoff, Robert D

    2012-03-01

    The aim of this was to define 30-day outcomes of patients treated with colectomy and en bloc pancreatectomy for invasive colon cancer. ACS NSQIP was used to identify patients who underwent colectomy and pancreatectomy concomitantly (n = 65) for colon carcinoma. Patients with en bloc pancreatectomy were compared to a propensity score-matched control group for 30-day outcomes. Sixteen patients underwent a pancreaticoduodenectomy with colectomy and 49 patients underwent a distal pancreatectomy with colectomy. There were 195 matched control patients. En bloc pancreatectomy (Whipple vs. distal pancreatectomy vs. control) patients had longer OR times (390 vs. 265 vs.137 min) and length of postoperative stay (12 vs. 10 vs. 6 days). The frequency of pulmonary complications (31.3% vs. 36.7% vs. 3.6%), blood transfusions (2.9 vs. 1.7 vs. 0.3 U), wound dehiscence, (18.8% vs. 6.12% vs.0.5%) and surgical site infection (43.5% vs. 34.7% vs.14.9%) were substantially higher in the pancreatectomy group (p < 0.05). There were no statistically significant differences in 30-day mortality between the pancreatectomy group and the control group (6.3% vs. 0% vs. 1.5% p = 0.25) Perioperative outcomes with en bloc pancreatectomy and colectomy include increased pulmonary complications, blood transfusions, wound complications, and length of stay compared to patients treated with colectomy alone for colon cancer.

  2. Application of nanoLC-ESI-TOF-MS for the metabolomic analysis of phenolic compounds from extra-virgin olive oil in treated colon-cancer cells.

    Science.gov (United States)

    Fernández-Arroyo, S; Gómez-Martínez, A; Rocamora-Reverte, L; Quirantes-Piné, R; Segura-Carretero, A; Fernández-Gutiérrez, A; Ferragut, J A

    2012-04-07

    Crude phenolic extracts (PE) have been obtained from naturally bearing Spanish extra-virgin olive oil (EVOO) showing different polyphenol families such as secoiridoids, phenolic alcohols, lignans, and flavones. EVOO-derived complex phenols (especially from the Arbequina variety olive) have been shown to suppress cell growth of SW480 and HT29 human colon adenocarcinoma cell lines. Inhibition of proliferation by EVOO-PE Arbequina variety extract was accompanied by apoptosis in both colon-cancer-cell lines and a limited G₂M cell-cycle arrest in the case of SW480 cells. The metabolized compounds from EVOO-PE in culture medium and cytoplasm of both cell lines were analyzed using nano-liquid chromatography (nanoLC) coupled with electrospray ionization-time-of-flight-mass spectrometry (ESI-TOF-MS). The results showed many phenolic compounds and their metabolites both in the culture medium as well as in the cytoplasm. The main compounds identified from EVOO-PE were hydroxylated luteolin and decarboxymethyl oleuropein aglycone. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Thiolated carboxymethyl dextran as a nanocarrier for colon delivery of hSET1 antisense: In vitro stability and efficiency study

    Energy Technology Data Exchange (ETDEWEB)

    Kiani, Melika, E-mail: Melika.kiani@gmail.com [Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran (Iran, Islamic Republic of); Mirzazadeh Tekie, Farnaz Sadat, E-mail: mirzazadehf@yahoo.com [Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran (Iran, Islamic Republic of); Dinarvand, Meshkat, E-mail: mdinarvand@hotmail.com [Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran (Iran, Islamic Republic of); Soleimani, Masoud, E-mail: soleim_m@modares.ac.ir [Stem Cell Technology Research Centre, P.O. Box 14155-3174, Tehran (Iran, Islamic Republic of); Department of Hematology, School of Medical Sciences, Tarbiat Modares University, P.O. Box: 14115-111, Tehran (Iran, Islamic Republic of); Dinarvand, Rassoul, E-mail: dinarvand@tums.ac.ir [Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran (Iran, Islamic Republic of); Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Atyabi, Fatemeh, E-mail: atyabifa@tums.ac.ir [Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran (Iran, Islamic Republic of); Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2016-05-01

    Gene therapy is an optimistic approach in cancer treatment. However, for efficient delivery of gene materials, designing an appropriate vector is necessary. Polyelectrolyte complexes (PECs) of chitosan and dextran could be considered a proper nanoparticulate carrier for sensitive biomaterials. In this study, PECs of chitosan and thiolated dextran were used as either an injectable or oral gene delivery system. hSET1 antisense was loaded into the PECs to suppress proliferation of colon cancer cell line. The prepared nanoparticles have ~ 115 nm diameter size and positive zeta potential with high mucoadhesion properties. They are able to protect antisense from degradation in serum and biorelevant fluids (FaSSIF and FaSSGF). Furthermore, prepared nanoparticles demonstrated superior cellular penetration and inhibitory effect on SW480 colon cancer cell proliferation. All nanoparticles significantly down regulated hSET1 in comparison with naked antisense. It can be concluded that thiolated PECs have potential use for injectable or oral delivery of nucleic acids such as antisense. - Highlights: • Formation of stable nanoparticle with dextran and chitosan derivatives for oral and intravenous gene delivery. • Satifactory cellular uptake of nanoparticles and approximately complete suppression of hSET1 expression in SW480 cell lines • Prolonged stability of nanoparticles against biorelevent media with desirable release rate.

  4. Voriconazole Exposure and Risk of Cutaneous Squamous Cell Carcinoma, Aspergillus Colonization, Invasive Aspergillosis and Death in Lung Transplant Recipients.

    Science.gov (United States)

    Mansh, M; Binstock, M; Williams, K; Hafeez, F; Kim, J; Glidden, D; Boettger, R; Hays, S; Kukreja, J; Golden, J; Asgari, M M; Chin-Hong, P; Singer, J P; Arron, S T

    2016-01-01

    Voriconazole is a triazole antifungal used to prevent and treat invasive fungal infections after lung transplantation, but it has been associated with an increased risk of developing cutaneous squamous cell carcinoma (SCC). Despite widespread use, there are no clear guidelines for optimal prophylactic regimens that balance the competing risks and benefits. We conducted a retrospective cohort study of all lung transplant recipients at the University of California, San Francisco, who were transplanted between October 1991 and December 2012 (n = 455) to investigate whether voriconazole exposure affected development of SCC, Aspergillus colonization, invasive aspergillosis and all-cause mortality. Voriconazole exposure was associated with a 73% increased risk of developing SCC (hazard ratio [HR] 1.73; 95% confidence interval [CI]: 1.04-2.88; p = 0.03), with each additional 30-day exposure at the standard dose increasing the risk by 3.0% (HR 1.03; 95% CI: 1.02-1.04; p Voriconazole exposure reduced risk of Aspergillus colonization by 50% (HR 0.50; 95% CI: 0.34-0.72; p Voriconazole exposure significantly reduced all-cause mortality among subjects who developed Aspergillus colonization (HR 0.34; 95% CI: 0.13-0.91; p = 0.03) but had no significant impact on those without colonization. Physicians should consider patient-specific factors that modify the potential risks and benefits of voriconazole for the care of lung transplant recipients. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  5. Energy restriction early in life and colon carcinoma risk: Results of The Netherlands Cohort Study after 7.3 years of follow-up

    NARCIS (Netherlands)

    Dirx, M.J.M.; Brandt, P.A. van den; Goldbohm, R.A.; Lumey, L.H.

    2003-01-01

    BACKGROUND. This study evaluated the effects of severe undernutrition during adolescence and subsequent colon carcinoma risk. METHODS. The authors evaluated The Netherlands Cohort Study on Diet and Cancer (NLCS) among 62,573 women and 58,279 men aged 55-69 years at baseline. Information on diet and

  6. TNFα cooperates with IFN-γ to repress Bcl-xL expression to sensitize metastatic colon carcinoma cells to TRAIL-mediated apoptosis.

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    Feiyan Liu

    Full Text Available BACKGROUND: TNF-related apoptosis-inducing ligand (TRAIL is an immune effector molecule that functions as a selective anti-tumor agent. However, tumor cells, especially metastatic tumor cells often exhibit a TRAIL-resistant phenotype, which is currently a major impediment in TRAIL therapy. The aim of this study is to investigate the synergistic effect of TNFα and IFN-γ in sensitizing metastatic colon carcinoma cells to TRAIL-mediated apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: The efficacy and underlying molecular mechanism of cooperation between TNFα and IFN-γ in sensitizing metastatic colon carcinoma cells to TRAIL-mediated apoptosis were examined. The functional significance of TNFα- and IFN-γ-producing T lymphocyte immunotherapy in combination with TRAIL therapy in suppression of colon carcinoma metastasis was determined in an experimental metastasis mouse model. We observed that TNFα or IFN-γ alone exhibits minimal sensitization effects, but effectively sensitized metastatic colon carcinoma cells to TRAIL-induced apoptosis when used in combination. TNFα and IFN-γ cooperate to repress Bcl-xL expression, whereas TNFα represses Survivin expression in the metastatic colon carcinoma cells. Silencing Bcl-xL expression significantly increased the metastatic colon carcinoma cell sensitivity to TRAIL-induced apoptosis. Conversely, overexpression of Bcl-xL significantly decreased the tumor cell sensitivity to TRAIL-induced apoptosis. Furthermore, TNFα and IFN-γ also synergistically enhanced TRAIL-induced caspase-8 activation. TNFα and IFN-γ was up-regulated in activated primary and tumor-specific T cells. TRAIL was expressed in tumor-infiltrating immune cells in vivo, and in tumor-specific cytotoxic T lymphocytes (CTL ex vivo. Consequently, TRAIL therapy in combination with TNFα/IFN-γ-producing CTL adoptive transfer immunotherapy effectively suppressed colon carcinoma metastasis in vivo. CONCLUSIONS/SIGNIFICANCE: TNFα and IFN

  7. TNFα Cooperates with IFN-γ to Repress Bcl-xL Expression to Sensitize Metastatic Colon Carcinoma Cells to TRAIL-mediated Apoptosis

    Science.gov (United States)

    Liu, Feiyan; Hu, Xiaolin; Zimmerman, Mary; Waller, Jennifer L.; Wu, Ping; Hayes-Jordan, Andrea; Lev, Dina; Liu, Kebin

    2011-01-01

    Background TNF-related apoptosis-inducing ligand (TRAIL) is an immune effector molecule that functions as a selective anti-tumor agent. However, tumor cells, especially metastatic tumor cells often exhibit a TRAIL-resistant phenotype, which is currently a major impediment in TRAIL therapy. The aim of this study is to investigate the synergistic effect of TNFα and IFN-γ in sensitizing metastatic colon carcinoma cells to TRAIL-mediated apoptosis. Methodology/Principal Findings The efficacy and underlying molecular mechanism of cooperation between TNFα and IFN-γ in sensitizing metastatic colon carcinoma cells to TRAIL-mediated apoptosis were examined. The functional significance of TNFα- and IFN-γ-producing T lymphocyte immunotherapy in combination with TRAIL therapy in suppression of colon carcinoma metastasis was determined in an experimental metastasis mouse model. We observed that TNFα or IFN-γ alone exhibits minimal sensitization effects, but effectively sensitized metastatic colon carcinoma cells to TRAIL-induced apoptosis when used in combination. TNFα and IFN-γ cooperate to repress Bcl-xL expression, whereas TNFα represses Survivin expression in the metastatic colon carcinoma cells. Silencing Bcl-xL expression significantly increased the metastatic colon carcinoma cell sensitivity to TRAIL-induced apoptosis. Conversely, overexpression of Bcl-xL significantly decreased the tumor cell sensitivity to TRAIL-induced apoptosis. Furthermore, TNFα and IFN-γ also synergistically enhanced TRAIL-induced caspase-8 activation. TNFα and IFN-γ was up-regulated in activated primary and tumor-specific T cells. TRAIL was expressed in tumor-infiltrating immune cells in vivo, and in tumor-specific cytotoxic T lymphocytes (CTL) ex vivo. Consequently, TRAIL therapy in combination with TNFα/IFN-γ-producing CTL adoptive transfer immunotherapy effectively suppressed colon carcinoma metastasis in vivo. Conclusions/Significance TNFα and IFN-γ cooperate to overcome

  8. Clinicopathological and prognostic significance of HER-2/neu and VEGF expression in colon carcinomas

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    Li Jing

    2011-06-01

    Full Text Available Abstract Background HER-2/neu and VEGF expression is correlated with disease behaviors in various cancers. However, evidence for their expression in colon cancer is rather contradictory both for the protein expression status and prognostic value. HER-2/neu is found to participate in VEGF regulation, and has known correlation with VEGF expression in some tumors. In this study, we investigated HER-2/neu and VEGF expression in Chinese colon patients and explored whether there was any correlation between their expression patterns. Methods HER-2/neu and VEGF were investigated immunohistochemically using tumor samples obtained from 317 colon cancer patients with all tumor stages. Correlation of the degree of staining with clinicopathological parameters and survival was investigated. Results Positive expression rates of HER-2/neu and VEGF in colon cancer were 15.5% and 55.5% respectively. HER-2/neu expression was significantly correlated with tumor size and distant metastases (P (P > 0.05. Expression of VEGF was significantly correlated with tumor size, tumor stage, lymph node metastases, and distant metastases (P (P = 0.146. No correlation between HER-2/neu and VEGF expression was detected (P = 0.151. Conclusions HER-2/neu and VEGF are not important prognostic markers of colon cancer. The present results do not support any association between HER2/neu and VEGF expression in this setting.

  9. Evaluation of the Combined Effects of Sonodynamic and Photodynamic Therapies in a Colon Carcinoma Tumor Model (CT26

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    Ameneh Sazgarnia

    2009-12-01

    Full Text Available Introduction: Photodynamic therapy is a noninvasive therapeutic method for tumors with a maximum depth of 5 mm. On the other hand, most photosensitizers are also susceptible to ultrasound waves (the basis of sonodynamic therapy. Therefore, it is expected that a combination of the two therapeutic methods will increase effectiveness of photodynamic therapies for lower doses of sensitizer and curing deeper tumors. This study evaluates the synergistic effects of photodynamic and sonodynamic therapies.     Materials and methods: The study was conducted on a colon carcinoma tumor model in Balb/c mice. The colon carcinoma tumors were induced in the mice by subcutaneous injection. Twenty four hours after intraperitoneal injection of Zinc Phthalocyanine liposome as a sensitizer, at first ultrasound irradiation with a known frequency and intensity was performed followed by illumination of the tumor area. Evaluation of the treatment efficacy was done using daily measurement of the tumors and calculation of their relative volumes. Also, all control groups were considered to confirm the effect of each therapeutic option in the study.   Results: In the first ten days post treatment, the relative volumes of all groups decreased significantly in comparison with the main control group, but the best response was observed in the photodynamic or sonodynamic therapy groups. The longest doubling time of tumor size was related to groups under photodynamic, sonodynamic and main therapies, and the shortest belonged to the control group.   Discussion and conclusion: Zinc phthalocyanine liposome is both a photosensitizer and sonsensitizer. Photodynamic and sonodynamic therapies can be efficient in retarding tumor growth rate. In this study, combination of the two methods did not cause improved therapeutic outcomes. It is predicted that this result is related to the choice of therapeutic agents and could be optimized in future.

  10. Gossypol sensitizes the antitumor activity of 5-FU through down-regulation of thymidylate synthase in human colon carcinoma cells.

    Science.gov (United States)

    Yang, Dan; Qu, Jinglei; Qu, Xiujuan; Cao, Yubo; Xu, Ling; Hou, Kezuo; Feng, Wanyu; Liu, Yunpeng

    2015-09-01

    5-Fluorouracil (5-FU) is the basic chemotherapeutic agent used to treat colon cancer. However, the sensitivity of colon cancer cells to 5-FU is limited. Gossypol is a polyphenolic extract of cottonseeds. The purpose of this study was to investigate the activities and related mechanism of gossypol alone or in combination with 5-FU against human colon carcinoma cells. The IC50 of gossypol or/and 5-FU in vitro was tested by 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, and the drug interaction was analyzed using the CalcuSyn method. Cell apoptosis was determined using presidium iodide staining and flow cytometric analysis. Western blotting was used to determine the expression of proteins. Transient transfection method was used to silence protein. The IC₅₀ at 48 h of gossypol in colon cancer cells was 26.11 ± 1.04 μmol/L in HT-29 cells, 14.11 ± 1.08 μmol/L in HCT116 cells, and 21.83 ± 1.05 μmol/L in RKO cells. When gossypol was combined with 5-FU, a synergistic cytotoxic effect was observed in HT-29 cells, HCT116 cells, and RKO cells compared with treatment with gossypol or 5-FU alone. The Western blotting results indicated that gossypol down-regulated thymidylate synthase (TS) rather than thymidine phosphorylase protein expression. Furthermore, the mTOR/p70S6K1 signaling pathway was inhibited in gossypol-treated colon cancer cells, and consequently, cyclin D1 expression was decreased, suggesting an additional mechanism of the observed antiproliferative synergistic interactions. All the observation was confirmed by silencing TS and inactivating the mTOR/p70S6K1 signaling pathway by rapamycin, both of which increased the chemo-sensitizing efficacy of 5-FU. These findings suggest that gossypol-mediated down-regulation of TS, cyclin D1, and the mTOR/p70S6K1 signaling pathways enhances the anti-tumor effect of 5-FU. Ultimately, our data exposed a new action for gossypol as an enhancer of 5-FU-induced cell growth suppression.

  11. The sentinel node procedure in colon carcinoma : a multi-centre study in The Netherlands

    NARCIS (Netherlands)

    Kelder, Wendy; Braat, Andries E.; Karrenbeld, Arend; Grond, Joris A. K.; De Vries, Johannes E.; Oosterhuis, J. Wolter A.; Baas, Peter C.; Plukker, John T. M.

    2007-01-01

    Background Lymph node status is the most important predictive factor in colorectal carcinoma. Recurrences occur in 20% of the patients without lymph node metastases. The sentinel lymph node (SLN) biopsy is a tool to facilitate identification of micrometastatic disease and aberrant lymphatic

  12. Animal products and K-ras codon 12 and 13 mutations in colon carcinomas

    NARCIS (Netherlands)

    Kampman, E.; Voskuil, D.W.; Kraats, van A.A.; Balder, H.F.; Muijen, van G.N.P.; Goldbohm, R.S.; Veer, van 't P.

    2000-01-01

    K-ras gene mutations (codons 12 and 13) were determined by PCR-based mutant allele-specific amplification (MASA) in tumour tissue of 185 colon cancer patients: 36␑arboured mutations, of which 82 ere located in codon 12. High intakes of animal protein, calcium and poultry were differently associated

  13. Apple polyphenols affect protein kinase C activity and the onset of apoptosis in human colon carcinoma cells.

    Science.gov (United States)

    Kern, Melanie; Pahlke, Gudrun; Balavenkatraman, Kamal Kumar; Böhmer, Frank D; Marko, Doris

    2007-06-27

    Polyphenol-rich apple extracts have been reported to suppress human colon cancer cell growth in vitro. The protein kinase C (PKC) is among the signaling elements known to play an important role in colon carcinogenesis. In the present study, we investigated whether apple polyphenols affect PKC activity and induce apoptosis in the human colon carcinoma cell line HT29. A polyphenol-rich apple juice extract (AE02) was shown to inhibit cytosolic PKC activity in a cell-free system. In contrast, incubation of HT29 cells for 1 or 3 h with AE02 up to 2 mg/mL did not affect the cytosolic PKC activity. After prolonged incubation (24 h), cytosolic PKC activity was modulated, albeit a u-shaped curve of effectiveness was observed, with an initial inhibitory effect followed by the recurrence and even induction of enzyme activity. Concomitantly, in the cytosol, a significant decrease of the protein levels of PKCalpha, PKCbetaII, and PKCgamma together with a significant increase of a proapoptotic PKCdelta fragment was observed. However, the effects on the protein levels of these PKC isoforms in the cytosol were not associated with translocation between the different cellular compartments but might instead result from the onset of apoptosis. Indeed, the treatment with AE02 was shown to induce apoptosis by the activation of caspase-3, DNA fragmentation, and cleavage of poly(ADP ribose) polymerase. So far, identified and available constituents of the apple extract did not contribute substantially to the observed effects on PKC and apoptosis induction. In summary, apple polyphenols were found to inhibit PKC activity in a cell-free system. However, our results indicate that within intact cells PKC does not represent the primary target of apple polyphenols but appears to be affected in the course of apoptosis induction.

  14. Multiplex flow cytometry barcoding and antibody arrays identify surface antigen profiles of primary and metastatic colon cancer cell lines.

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    Kumar Sukhdeo

    Full Text Available Colon cancer is a deadly disease affecting millions of people worldwide. Current treatment challenges include management of disease burden as well as improvements in detection and targeting of tumor cells. To identify disease state-specific surface antigen signatures, we combined fluorescent cell barcoding with high-throughput flow cytometric profiling of primary and metastatic colon cancer lines (SW480, SW620, and HCT116. Our multiplexed technique offers improvements over conventional methods by permitting the simultaneous and rapid screening of cancer cells with reduced effort and cost. The method uses a protein-level analysis with commercially available antibodies on live cells with intact epitopes to detect potential tumor-specific targets that can be further investigated for their clinical utility. Multiplexed antibody arrays can easily be applied to other tumor types or pathologies for discovery-based approaches to target identification.

  15. Prostaglandin E2 Activates YAP and a Positive-Signaling Loop to Promote Colon Regeneration After Colitis but Also Carcinogenesis in Mice.

    Science.gov (United States)

    Kim, Han-Byul; Kim, Minchul; Park, Young-Soo; Park, Intae; Kim, Tackhoon; Yang, Sung-Yeun; Cho, Charles J; Hwang, DaeHee; Jung, Jin-Hak; Markowitz, Sanford D; Hwang, Sung Wook; Yang, Suk-Kyun; Lim, Dae-Sik; Myung, Seung-Jae

    2017-02-01

    Prostaglandin E2 (PGE2) is mediator of inflammation that regulates tissue regeneration, but its continual activation has been associated with carcinogenesis. Little is known about factors in the PGE2 signaling pathway that contribute to tumor formation. We investigated whether yes-associated protein 1 (YAP1), a transcriptional co-activator in the Hippo signaling pathway, mediates PGE2 function. DLD-1 and SW480 colon cancer cell lines were transfected with vectors expressing transgenes or small hairpin RNAs and incubated with recombinant PGE2, with or without pharmacologic inhibitors of signaling proteins, and analyzed by immunoblot, immunofluorescence, quantitative reverse-transcription polymerase chain reaction, transcriptional reporter, and proliferation assays. Dextran sodium sulfate (DSS) was given to induce colitis in C57/BL6 (control) mice, as well as in mice with disruption of the hydroxyprostaglandin dehydrogenase 15 gene (15-PGDH-knockout mice), Yap1 gene (YAP-knockout mice), and double-knockout mice. Some mice also were given indomethacin to block PGE2 synthesis. 15-PGDH knockout mice were crossed with mice with intestine-specific disruption of the salvador family WW domain containing 1 gene (Sav1), which encodes an activator of Hippo signaling. We performed immunohistochemical analyses of colon biopsy samples from 26 patients with colitis-associated cancer and 51 age-and sex-matched patients with colorectal cancer (without colitis). Incubation of colon cancer cell lines with PGE2 led to phosphorylation of cyclic adenosine monophosphate-responsive element binding protein 1 and increased levels of YAP1 messenger RNA, protein, and YAP1 transcriptional activity. This led to increased transcription of the prostaglandin-endoperoxide synthase 2 gene (PTGS2 or cyclooxygenase 2) and prostaglandin E-receptor 4 gene (PTGER4 or EP4). Incubation with PGE2 promoted proliferation of colon cancer cell lines, but not cells with knockdown of YAP1. Control mice developed

  16. Ultraviolet A eye irradiation ameliorates colon carcinoma induced by azoxymethane and dextran sodium sulfate through β-endorphin and methionine-enkephalin.

    Science.gov (United States)

    Hiramoto, Keiichi; Yokoyama, Satoshi; Yamate, Yurika

    2017-03-01

    We previously reported that ultraviolet (UV) A eye irradiation reduces the ulcerative colitis induced by dextran sodium sulfate (DSS). This study examined the effects of UVA on colon carcinoma induced by azoxymethane (AOM) and DSS. We irradiated the eyes of ICR mice with UVA at a dose of 110 kJ/m2 using an FL20SBLB-A lamp for the experimental period. In mice treated with these drugs, the symptom of colon carcinoma was reduced by UVA eye irradiation. The levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α in the blood were increased in AOM + DSS-treated mice; however, those levels were reduced by UVA eye irradiation. The expression of β-endorphin, methionine-enkephalin (OGF), μ-opioid receptor, and opioid growth factor receptor (OGFR) of the colon was increased in the AOM + DSS-treated mice, and these levels were increased further following UVA eye irradiation. When β-endorphin inhibitor was administered, the ameliorative effect of UVA eye irradiation was reduced, and the effect of eye irradiation disappeared entirely following the administration of naltrexone (inhibitor of both opioid receptor and OGFR). These results suggested that UVA eye irradiation exerts major effects on AOM + DSS-induced colon carcinoma. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. ALDH1B1 Is Crucial for Colon Tumorigenesis by Modulating Wnt/β-Catenin, Notch and PI3K/Akt Signaling Pathways.

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    Surendra Singh

    Full Text Available In the normal human colon, aldehyde dehydrogenase 1B1 (ALDH1B1 is expressed only at the crypt base, along with stem cells. It is also highly expressed in the human colonic adenocarcinomas. This pattern of expression corresponds closely to that observed for Wnt/β-catenin signaling activity. The present study examines the role of ALDH1B1 in colon tumorigenesis and signalling pathways mediating its effects. In a 3-dimensional spheroid growth model and a nude mouse xenograft tumor model, shRNA-induced suppression of ALDH1B1 expression decreased the number and size of spheroids formed in vitro and the size of xenograft tumors formed in vivo by SW 480 cells. Six binding elements for Wnt/β-catenin signalling transcription factor binding elements (T-cell factor/lymphoid enhancing factor were identified in the human ALDH1B1 gene promoter (3 kb but shown by dual luciferase reporter assay to not be necessary for ALDH1B1 mRNA expression in colon adenocarcinoma cell lines. We examined Wnt-reporter activity and protein/mRNA expression for Wnt, Notch and PI3K/Akt signaling pathways. Wnt/β-catenin, Notch and PI3K/Akt-signaling pathways were down-regulated in SW 480 cells in which ALDH1B1 expression had been suppressed. In summary, our data demonstrate that ALDH1B1 may promote colon cancer tumorigenesis by modulating the Wnt/β-catenin, Notch and PI3K/Akt signaling pathways. Selective targeting of ALDH1B1 may represent a novel means to prevent or treat colon cancer.

  18. Signet ring cell carcinoma of the colon in a 10 year-old boy

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    Irene Irene

    2011-04-01

    polyposis and ulcerative colitis. However, carcinoma arising de novo is the most common type.2,3 Risk factors include a high caloric diet rich in animal fat, sedentary lifestyle, smoking, alcohol consumption, low vegetable fibre consumption, chronic inflammatory bowel disease, ulcerative colitis, Crohn's disease, and polymorphism in key enzymes of injurious compounds.s

  19. A 36-year-old female with Krukenberg tumor from a colonic carcinoma

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    Srikanth Umakanthan

    2015-01-01

    Full Text Available Krukenberg tumor is bilateral ovarian carcinoma′s metastasizing most commonly from a gastric primary followed by a colon. We report a case of 36-year-old female with bilateral ovarian mass diagnosed as Krukenberg with a work up for locating the primary site. In this case, we discuss widely the clinical aspects with histopathological features and literature review of Krukenberg tumor.

  20. Carcinoma of sigmoid colon following urinary diversion: a case report and review of literature

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    Naqvi Abul H

    2004-06-01

    Full Text Available Abstract Background The association of ureterosigmoidostomy with colonic cancer is well established. A 100-fold increased risk of malignancy has been proposed in association with ureterosigmoidostomy. Characteristically there is a latent period of around 20–30 years before the occurrence of cancer. Case presentation An unusual case of adenocarcinoma of the colon in a 36-year-old patient is presented. The patient underwent three operations in his infancy for exstrophy but after failure to close bladder, ureterosigmoidostomy was attempted at the age of 5 years and was converted to an ileal conduit after 8 months. At the age of 36 years, 30 years following ileal conduit urinary diversion for exstrophy, he presented in emergency with large bowel obstruction due to adenocarcinoma of the sigmoid colon. Conclusion Patients who undergo urinary diversion for exstrophy may be kept on a regular follow-up surveillance colonoscopy as most of these young adults may later present with vague abdominal symptoms which may not be taken seriously until they increase to an extent as to present with intestinal obstruction as in the present case.

  1. Targeted chemotherapy against intraperitoneally disseminated colon carcinoma using a cationized gelatin-conjugated HVJ envelope vector.

    Science.gov (United States)

    Mima, Hidetoshi; Yamamoto, Seiji; Ito, Makoto; Tomoshige, Ryuji; Tabata, Yasuhiko; Tamai, Katsuto; Kaneda, Yasufumi

    2006-04-01

    The hemagglutinating virus of Japan envelope (HVJ-E; Sendai virus) vector derived from inactivated HVJ particles can be used to deliver DNA, proteins, and drugs into cells both in vitro and in vivo. HVJ-E is capable of delivering bleomycin, an anticancer drug, to various cancer cell lines, thereby producing 300-fold greater cytotoxicity than administration of bleomycin alone. In a mouse model of peritoneally disseminated colon cancer, we injected HVJ-E containing the luciferase gene into the peritoneum. Unexpectedly, luciferase gene expression was not observed within the tumor deposits or any organs. However, when combined with cationized gelatin (CG), CG-HVJ-E produced a high level of luciferase gene expression primarily within the tumor deposits. Forty-eight hours after introducing colon cancer cells into the peritoneum of experimental mice, CG-HVJ-E with or without bleomycin was injected into the abdominal cavity. Following six injections of bleomycin-incorporated CG-HVJ-E, complete responses were observed in 40% of the mice examined. All of the mice that received either empty CG-HVJ-E or bleomycin alone died within 40 days of having cancer cells introduced into the peritoneum. When the mice with complete responses were rechallenged with colon cancer cells from the same cell line, no tumors developed. Thus, CG-HVJ-E may suppress peritoneal dissemination of cancer.

  2. Cytotoxicity and Apoptotic Effects of Polyphenols from Sugar Beet Molasses on Colon Carcinoma Cells in Vitro

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    Mingshun Chen

    2016-06-01

    Full Text Available Three polyphenols were isolated and purified from sugar beet molasses by ultrasonic-aid extraction and various chromatographic techniques, and their structures were elucidated by spectral analysis. Cytotoxicity and the molecular mechanism were measured by methyl thiazolyl tetrazolium (MTT assay, flow cytometry, caspase-3 activity assay and Western blot assay. The results showed that gallic acid, cyanidin-3-O-glucoside chloride and epicatechin have cytotoxicity to the human colon, hepatocellular and breast cancer cells. Cyanidin-3-O-glucoside chloride showed its cytotoxicity against various tumor cell lines, particularly against colon cancer Caco-2 cells with half maximal inhibitory concentration (IC50 value of 23.21 ± 0.14 μg/mL in vitro. Cyanidin-3-O-glucoside chloride may be a potential candidate for the treatment of colon cancer. In the mechanism study, cyanidin-3-O-glucoside chloride increased the ratio of cell cycle at G0/G1 phase and reduced cyclin D1 expression on Caco-2 cells. Cyanidin-3-O-glucoside chloride decreased mutant p21 expression, and increased the ratio of Bax/Bcl-2 and the activation of caspase-3 to induce apoptosis.

  3. Native Valve Streptococcus bovis Endocarditis and Refractory Transfusion Dependent Iron Deficiency Anaemia Associated with Concomitant Carcinoma of the Colon: A Case Report and Review of the Literature

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    Abdul Azeez Ahamed Riyaaz

    2016-01-01

    Full Text Available Streptococcus bovis is found as a commensal organism in human gut and may become opportunistically pathogenic. Infective endocarditis is one of the commonest modes of presentation of this infection. The association between Streptococcus bovis endocarditis and colorectal cancer is well recognized. We report a case of Streptococcus bovis endocarditis along with a refractory iron deficiency anaemia associated with concomitant carcinoma of ascending colon in a 63-year-old male. Cooccurrence of these two conditions may cause a challenge in the management. Considering the strong association of colon cancer with Streptococcus bovis endocarditis, a detailed screening colonoscopy is mandatory following the diagnosis of the latter.

  4. Colon-derived liver metastasis, colorectal carcinoma, and hepatocellular carcinoma can be discriminated by the Ca(2+-binding proteins S100A6 and S100A11.

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    Christian Melle

    Full Text Available BACKGROUND: It is unknown, on the proteomic level, whether the protein patterns of tumors change during metastasis or whether markers are present that allow metastases to be allocated to a specific tumor entity. The latter is of clinical interest if the primary tumor is not known. METHODOLOGY/PRINCIPAL FINDINGS: In this study, tissue from colon-derived liver metastases (n = 17 were classified, laser-microdissected, and analysed by ProteinChip arrays (SELDI. The resulting spectra were compared with data for primary colorectal (CRC and hepatocellular carcinomas (HCC from our former studies. Of 49 signals differentially expressed in primary HCC, primary CRC, and liver metastases, two were identified by immunodepletion as S100A6 and S100A11. Both proteins were precisely localized immunohistochemically in cells. S100A6 and S100A11 can discriminate significantly between the two primary tumor entities, CRC and HCC, whereas S100A6 allows the discrimination of metastases and HCC. CONCLUSIONS: Both identified proteins can be used to discriminate different tumor entities. Specific markers or proteomic patterns for the metastases of different primary cancers will allow us to determine the biological characteristics of metastasis in general. It is unknown how the protein patterns of tumors change during metastasis or whether markers are present that allow metastases to be allocated to a specific tumor entity. The latter is of clinical interest if the primary tumor is not known.

  5. Is the Longitudinal Margin of Carcinoma-Bearing Colon Resections a Neglected Parameter?

    DEFF Research Database (Denmark)

    Rørvig, Sara; Schlesinger, Nis; Mårtensson, Nina Løth

    2014-01-01

    BACKGROUND: Resection of colon cancer with curative intent implies clear margins. An arbitrary requirement of 2 cm DtLM generally ensures surgical and pathological clearance. However, harvest of tumor-draining lymph nodes is related to DtLM. For this reason, an extended longitudinal margin becomes......% of the specimens. Sixty-three and 83.5% of the cancer specimens with DtLM ... in relation to pT stage. CONCLUSION: This study suggests that DtLM cancer surgery might result in diagnostic "understaging" and hence leaving metastasis in the patient....

  6. Cytotoxicity effect of Zataria multiflora Boiss. on two human colon carcinoma cell lines

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    F. Sharififar

    2017-10-01

    Full Text Available Background and objectives: Natural products are one of the major sources for investigations of novel medicines. Zataria multiflora Boiss (ZM has shown pharmacological activities especially in gastrointestinal tract; however, there are limited studies about its cytotoxicity effects. In this study, the effect of Zataria multiflora was examined on two colon cancer cell lines (SW-48 and HT-29. Methods: Hydro-alcoholic extract of ZM and its fractions including chloroform, petroleum ether and methanol extract were prepared by warm maceration method. Different concentrations were prepared and examined on SW-48 and HT-29 cell lines using 2-(4, 5-dimethylthiazol-2-yl 2, 5-diphenyltetrazolium bromide (MTT assay. Results: The results of the present study have shown the cytotoxic effect of some fractions of ZM. The most considerable cytotoxic effect was shown against HT-29 cell line. Also, total ZM extract and the petroleum ether fraction demonstrated cytotoxic effects with IC50 values of 44.22 and 33.42 µg/ml on SW-48 and HT-29 cell lines, respectively. Conclusion: Zataria multiflora was cytotoxic to against colon cancer cell lines HT-29 and SW-48.

  7. CF101, An Agonist to the A3 Adenosine Receptor, Enhances the Chemotherapeutic Effect of 5-Fluorouracil in a Colon Carcinoma Murine Model

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    Sara Bar-Yehuda

    2005-01-01

    Full Text Available NF-κB and the upstream kinase PKB/Akt are highly expressed in chemoresistance tumor cells and may hamper the apoptotic pathway. CF101, a specific agonist to the A3 adenosine receptor, inhibits the development of colon carcinoma growth in cell cultures and xenograft murine models. Because CF101 has been shown to downregulate PKB/Akt and NF-κB protein expression level, we presumed that its combination with chemotherapy will enhance the antitumor effect of the cytotoxic drug. In this study, we utilized 3-[4,5Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT and colony formation assays and a colon carcinoma xenograft model. It has been shown that a combined treatment of CF101 and 5-fluorouracil (5-FU enhanced the cytotoxic effect of the latter on HCT-116 human colon carcinoma growth. Downregulation of PKB/Akt, NF-κB, and cyclin D1, and upregulation of caspase-3 protein expression level were observed in cells and tumor lesions on treatment with a combination of CF101 and 5-FU. Moreover, in mice treated with the combined therapy, myelotoxicity was prevented as was evidenced by normal white blood cell and neutrophil counts. These results show that CF101 potentiates the cytotoxic effect of 5-FU, thus preventing drug resistance. The myeloprotective effect of CF101 suggests its development as an add-on treatment to 5-FU.

  8. Antiproliferative effects on colon adenocarcinoma cells induced by co-administration of vitamin K1 and Lactobacillus rhamnosus GG.

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    Orlando, Antonella; Linsalata, Michele; Russo, Francesco

    2016-06-01

    Vitamin K (VK), an essential nutrient associated with the clotting cascade, has also been demonstrated to have anticancer properties in various cancer cells including colon cancer cells. Also probiotics have gained interest as potential anticancer agents. Among them, Lactobacillus rhamnosus GG (L.GG) has been shown to inhibit cell proliferation and polyamine biosynthesis as well as to induce apoptosis in different human gastrointestinal cancer cells. Nevertheless, the exact mechanisms involved in these actions are not completely elucidated. Therefore, the aims of the present study were to evaluate in three differently graded human colon cancer cells (namely Caco-2, HT-29 and SW480) the effects of increasing VK1 concentrations, administered alone or in combination with viable L.GG, on the cell proliferation evaluated by MTT test, apoptosis investigated by Bax/Bcl-2 ratio and the percentage of the apoptotic cells, and the cell cycle evaluated by MUSE cell analyzer. Both VK1 and L.GG administered alone up to 72 h, caused inhibition of proliferation, induction of apoptosis and the cell cycle arrest in all the tested colon cancer cells. When VK1 and L.GG were co-administered, the addition of increasing VK1 concentrations potentiated the probiotic antiproliferative effect in a dose-dependent manner, being also related to the individual features of each cell line. The effect was more evident in Caco-2 and HT-29 cells compared to the less differentiated SW480. The enhanced antiproliferative efficacy due to co-administration of L.GG and VK1 could represent a suitable option in a functional food strategy for cancer growth inhibition and chemoprevention.

  9. Mucinous cystadenoma of the appendix associated with adenocarcinoma of the sigmoid colon and hepatocellular carcinoma of the liver: Report of a case

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    Djuranovic, Srdjan P; Spuran, Milan M; Kovacevic, Nada V; Ugljesic, Milenko B; Kecmanovic, Dragutin M; Micev, Marjan T

    2006-01-01

    Mucinous cystadenoma of the appendix is a rare condition and represents one of the three entities with the common name mucocele of the appendix. It is characterized by a cystic dilatation of the lumen with stasis of mucus inside it. Histopathologically mucocele is divided into three groups: focal or diffuse mucosal hyperplasia, mucinous cystadenoma and mucinous cystadenocarcinoma. This condition is often associated with other neoplasia, especially adenocarcinoma of the colon and ovaries. We here describe a 57 year old male patient who presented with abdominal discomfort, constipation, fresh blood in stool and frequent urination. He had a big cystadenoma of the appendix associated with adenocarcinoma of the colon and hepatocellular carcinoma of the liver. The patient underwent right haemicolectomy, sigmoid colon resection and segmental resection of the liver. Now 3 years later he has no evidence of disease relapse. According to this, we stress the need of accurate preoperative diagnosis and intraoperative exploration of the whole abdomen in these patients. PMID:16610012

  10. Hyperplastic polyps of the colon and rectum - reclassification, BRAF and KRAS status in index polyps and subsequent colorectal carcinoma.

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    Janjua, Huma Gul Rehana; Høgdall, Estrid; Linnemann, Dorte

    2015-04-01

    Hyperplastic polyps (HP) of the colon and rectum were previously considered benign. Newer studies have suggested that colorectal HP are different entities. The aim of this study was to reclassify lesions from a 5-year period previously classified as colorectal HP into traditional hyperplastic polyp (THP), sessile serrated lesions (SSL), and other lesions. All patients were confirmed in the Danish National Pathology Database for the occurrence of metachronous polyps/adenomas, colorectal cancer (CRC), and other gastrointestinal malignancies. Molecular pathology of the CRC were characterized and correlated with the index lesion. In total, 591 HP biopsy specimens were obtained from 480 patients. The lesions were reclassified as: 358 THP, 109 SSL, 35 TA, 81 unspecified non-neoplastic lesions, four traditional serrated adenoma, and 4 SSL with cytological dysplasia. Seven patients developed CRC in the follow-up period (1 patient had SSL, 4 had THP, and 2 had unspecified non-neoplastic lesions). Ten patients developed other gastrointestinal malignancies. The patient with SSL as index lesions who developed CRC harbored V600E BRAF mutation in both index lesion and the carcinoma. Sixteen percent of patients with SSL subsequently developed a neoplastic lesion. Further studies are needed to clarify the cancer risk of SSL. © 2015 APMIS. Published by John Wiley & Sons Ltd.

  11. A bipartite butyrate-responsive element in the human calretinin (CALB2) promoter acts as a repressor in colon carcinoma cells but not in mesothelioma cells.

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    Häner, Katrin; Henzi, Thomas; Pfefferli, Martine; Künzli, Esther; Salicio, Valerie; Schwaller, Beat

    2010-02-15

    The short-chain fatty acid butyrate plays an essential role in colonic mucosa homeostasis through the capacity to block the cell cycle, regulate differentiation and to induce apoptosis. The beneficial effect of dietary fibers on preventing colon cancer is essentially mediated through butyrate, derived from luminal fermentation of fibers by intestinal bacteria. In epithelial cells of the colon, both in normal and colon cancer cells, the expression of several genes is positively or negatively regulated by butyrate likely through modulation of histone acetylation and thereby affecting the transcriptional activity of genes. Calretinin (CALB2) is a member of the EF-hand family of Ca(2+)-binding proteins and is expressed in a majority of poorly differentiated colon carcinoma and additionally in mesothelioma of the epithelioid and mixed type. Since CALB2 is one of the genes negatively regulated by butyrate in colon cancer cells and butyrate decreases calretinin protein expression levels in those cells, we investigated whether expression is regulated via putative butyrate-responsive elements (BRE) in the human CALB2 promoter. We identified two elements that act as butyrate-sensitive repressors in all colon cancer cell lines tested (CaCo-2, HT-29, Co-115/3). In contrast, in cells of mesothelial origin, MeT-5A and ZL34, the same two elements do not operate as butyrate-sensitive repressors and calretinin expression levels are insensitive to butyrate indicative of cell type-specific regulation of the CALB2 promoter. Calretinin expression in colon cancer cells is negatively regulated by butyrate via a bipartite BRE flanking the TATA box and this may be linked to butyrate's chemopreventive activity. (c) 2009 Wiley-Liss, Inc.

  12. Signet-Ring Cell Carcinoma of the Colon: A Case Report and Review of the Literature

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    Peter Y. Park

    2015-11-01

    Full Text Available Background: Colorectal adenocarcinoma (CRC is the third leading cause of death in the United States. One of the histologic subtypes of CRC is signet-ring cell carcinoma (SRCC, which has a distinct molecular and tumor biology from that of adenocarcinoma. Primary SRCC diagnosed at an early stage is very rare as most cases are detected at an advanced stage. Therefore, overall prognosis of SRCC is poor. Case Presentation: A 36-year-old female presented to her primary care physician with new-onset progressive right lower quadrant pain without any significant past medical or family history. Computed tomography scan of the abdomen and pelvis with contrast showed a 4.9 × 3.5 × 3.1 cm, lobulated, septated cystic mass arising from the cecum. The mass demonstrated wall enhancement and contained focal areas of coarse calcification. There was nodal involvement either locally or distally. The patient underwent right hemicolectomy, and pathology revealed a high-grade mucinous carcinoma with signet-ring cell variant invading through the muscularis propria and into the subserosal adipose tissue. The margins were negative for tumor, and no lymphovascular or perineural invasion was noted. None of the 14 resected pericolonic lymph nodes was positive for malignancy. Hence, she was staged as pT3, pN0, pMx-stage IIA. The appendix was not involved. Microsatellite instability testing showed the preservation of MLH1, PMS2, MSH2 and MSH6 proteins by IHC and PCR. Carcinoembryonic antigen level was within normal limits. Due to the patient's young age, aggressive histology and microsatellite-stable status, adjuvant fluropyrimidine (5-FU-based therapy with the single agent capecitabine was initiated. The patient completed 6 months of adjuvant therapy and has been disease free for approximately 18 months. Conclusion: Primary SRCC of the cecum is a rare disease. Given the poor prognosis of these patients, early-stage disease with microsatellite-stable patients should be

  13. S18 family of mitochondrial ribosomal proteins: evolutionary history and Gly132 polymorphism in colon carcinoma.

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    Mushtaq, Muhammad; Ali, Raja Hashim; Kashuba, Vladimir; Klein, George; Kashuba, Elena

    2016-08-23

    S18 family of mitochondrial ribosomal proteins (MRPS18, S18) consists of three members, S18-1 to -3. Earlier, we found that overexpression of S18-2 protein resulted in immortalization and eventual transformation of primary rat fibroblasts. The S18-1 and -3 have not exhibited such abilities. To understand the differences in protein properties, the evolutionary history of S18 family was analyzed. The S18-3, followed by S18-1 and S18-2 emerged as a result of ancient gene duplication in the root of eukaryotic species tree, followed by two metazoan-specific gene duplications. However, the most conserved metazoan S18 homolog is the S18-1; it shares the most sequence similarity with S18 proteins of bacteria and of other eukaryotic clades. Evolutionarily conserved residues of S18 proteins were analyzed in various cancers. S18-2 is mutated at a higher rate, compared with S18-1 and -3 proteins. Moreover, the evolutionarily conserved residue, Gly132 of S18-2, shows genetic polymorphism in colon adenocarcinomas that was confirmed by direct DNA sequencing.Concluding, S18 family represents the yet unexplored important mitochondrial ribosomal proteins.

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

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    Joshua E Allen

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

  15. Defensin alpha 6 (DEFA 6 overexpression threshold of over 60 fold can distinguish between adenoma and fully blown colon carcinoma in individual patients

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    Greulich Karl

    2010-10-01

    Full Text Available Abstract Background It is known that alpha-defensin expression is enhanced in colon cancer. However, the expression of human alpha defensin 6 (DEFA 6 in earlier stages, such as adenoma, has so far not yet been studied in a patient resolved manner. Methods By using quantitative Real Time-PCR, the gene expression pattern of DEFA 1-3 and DEFA 6 was analyzed in tissue of different stages of carcinogenesis, derived from colorectal cancer patients. In addition to paired normal and tumor tissue, matched normal near tumor and adenoma tissue samples were examined. Results The median gene expression of human defensin alpha 6 (DEFA 6 has been found to be moderately increased (~ 5 fold in tumor samples derived from individuals with colorectal cancer (CRC when compared to their normal counterparts. However, when the data were analyzed in a patient-wise manner, a large expression variation among individual patients is found, making the use of DEFA 6 for individual diagnosis of fully blown colon carcinoma difficult. Surprisingly, in adenoma the gene expression analysis revealed a 100 fold increased median expression of DEFA 6 relative to normal colon tissue. 13/18 samples had an individual overexpression of more than 60 fold in adenoma but only 3/17 in carcinoma. In each of the individual patients, at least either the adenoma or the carcinoma showed strong DEFA 6 overexpression. Conclusions We suggest that the expression of DEFA 6 preferably can be used as a potential diagnostic marker for adenoma and not as a marker for fully blown carcinoma. This is supported by the fact that DEFA 6 is a downstream target of the Wnt pathway, which is mutational active during the earliest stage of cancer development.

  16. Comparative efficacy of 5flourouracil/calcium leucovorine versus 5flourouracil/calcium leucovorine plus oxaliplatin in the adjuvant treatment of colonic carcinoma in Kashmir

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    Hamid Deva Shaiq

    2013-01-01

    Full Text Available Aim: This prospective, randomized comparative study conducted in Kashmir evaluated the clinical profile of colonic carcinoma and the efficacy, side effects and survival advantage of adjuvant treatment with 5FU/CLV versus FOLFOX7. Materials and Methods: Between 2007 and 2009, the clinical profiles of 50 patients enrolled and randomized equally into Arm A receiving 5FU/CLV alone (Mayo Clinic Regimen and Arm B receiving the FOLFOX7 regimen (including oxaliplatin were evaluated. Results: Majority of the patients were in the 5 th and 6 th decade of life (males 70% versus females 30%, and most were from urban dwellings. Consumption of red meat, obesity and physical inactivity were common risk factors. A family history of colonic carcinoma was reported in 12% of the patients. Event-free and disease-free survival for the two arms were: Arm A - 12.8 ± 5 months and 14.2 ± 6 months; Arm B - 13.0 ± 6.7 months and 13.1 ± 6 months, respectively. Treatment-related morbidity was significant in Arm B whereas general well being and surrogate laboratory markers including a hemogram, favored Arm A. Conclusion: The clinical profile, risk factors and familial predisposition of Kashmiri colonic carcinoma patients matches that of colon cancer patients elsewhere. There was no added survival advantage by adding oxaliplatin to 5FU and CLV. Although the interim results showed that the Mayo Clinic Regimen has a better total survival advantage compared with the FOLFOX7 regimen, the results were not statistically significant. The Mayo Clinic Regimen was better than the FOLFOX7 regimen in terms of the toxicity profile. However, this finding needs to be studied further. The main idea of conducting this study was to reveal that there is no added advantage of adding oxaliplatin to 5FU and CLV, thereby (a reducing the toxicity (b and lowering cost of therapy.

  17. Fatty acid composition and anticancer activity in colon carcinoma cell lines of Prunus dulcis seed oil.

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    Mericli, Filiz; Becer, Eda; Kabadayı, Hilal; Hanoglu, Azmi; Yigit Hanoglu, Duygu; Ozkum Yavuz, Dudu; Ozek, Temel; Vatansever, Seda

    2017-12-01

    Almond oil is used in traditional and complementary therapies for its numerous health benefits due to high unsaturated fatty acids content. This study investigated the composition and in vitro anticancer activity of almond oil from Northern Cyprus and compared with almond oil from Turkey. Almond oil from Northern Cyprus was obtained by supercritical CO2 extraction and analyzed by GC-MS. Almond oil of Turkey was provided from Turkish pharmacies. Different concentrations of almond oils were incubated for 24 and 48 h with Colo-320 and Colo-741 cells. Cell growth and cytotoxicity were measured by MTT assays. Anticancer and antiprolifetarive activities of almond oils were investigated by immunocytochemistry using antibodies directed against to BMP-2, β-catenin, Ki-67, LGR-5 and Jagged 1. Oleic acid (77.8%; 75.3%), linoleic acid (13.5%; 15.8%), palmitic acid (7.4%; 6.3%), were determined as the major compounds of almond oil from Northern Cyprus and Turkey, respectively. In the MTT assay, both almond oils were found to be active against Colo-320 and Colo-741 cells with 1:1 dilution for both 24 h and 48 h. As a result of immunohistochemical staining, while both almond oils exhibited significant antiproliferative and anticancer activity, these activities were more similar in Colo-320 cells which were treated with Northern Cyprus almond oil. Almond oil from Northern Cyprus and Turkey may have anticancer and antiproliferative effects on colon cancer cells through molecular signalling pathways and, thus, they could be potential novel therapeutic agents.

  18. Inhibitory Effects of Probiotic Lactobacillus on the Growth of Human Colonic Carcinoma Cell Line HT-29

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    Zhung-Yuan Chen

    2017-01-01

    Full Text Available This study was conducted to investigate the inhibitory effect of Lactobacillus cells and supernatants on the growth of the human colon cancer cell line HT-29. Our study results indicated that the PM153 strain exhibits the best adhesion ability and the highest survival in the gastrointestinal tract simulation experiment. Furthermore, after an 8-h co-culture of PM153 and HT-29 cells, the PM153 strain can induce the secretion of nitric oxide from the HT-29 cells. In addition, after the co-culture of the BCRC17010 strain (109 cfu/mL and HT-29 cells, the Bax/Bcl-2 ratio in the HT-29 cells was 1.19, which showed a significant difference from the other control and LAB groups (p < 0.05, which therefore led to the inference that the BCRC17010 strain exerts a pro-apoptotic effect on the HT-29 cells. Upon co-culture with HT-29 cells for 4, 8 and 12 h, the BCRC14625 strain (109 cfu/mL demonstrated a significant increase in lactate dehydrogenase (LDH activity (p < 0.05, causing harm to the HT-29 cell membrane; further, after an 8-h co-culture with the HT-29 cells, it induced the secretion of nitric oxide (NO from the HT-29 cells. Some lactic acid bacteria (LAB strains have ability to inhibit the growth of the colorectal cancer cell line HT-29 Bax/Bcl-2 pathway or NO production. In summary, we demonstrated that the BCRC17010 strain, good abilities of adhesion and increased LDH release, was the best probiotic potential for inhibition of HT-29 growth amongst the seven LAB strains tested in vitro.

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

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    Yu-Lin Lin

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

  20. Synchronous cecal adenocarcinoma and multiple colonic in situ carcinomas in hamartomatous polyps in a case of isolated Peutz–Jeghers syndrome

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    Yahia Z Gad

    2011-03-01

    Full Text Available Yahia Z Gad1, Doaa H Bakr1, Mohammad G El-Ebeidy21Department of Internal Medicine, 2Department of Surgery, Mansoura Specialized Medical Hospital, Mansoura University, Mansoura, EgyptBackground: Peutz–Jeghers syndrome (PJS is a rare autosomal dominant disease characterized by mucocutaneous pigmentation and hamartomatous polyps of the entire gastrointestinal tract. A Peutz–Jeghers polyp (PJP in a patient without pigmentation or a family history of the disease is called an isolated or solitary PJP. Individuals with PJS carry a very high risk of developing gastrointestinal (GI as well as extra-GI malignancies. This case report documents lesion multiplicity and their malignant potential in a young patient with PJS presenting in a serious condition for the first time.Case report: An 18-year-old female Egyptian patient was admitted with hematochezia and remarkable anemia. After appropriate resuscitation and consent, colonoscopic evaluation revealed seven pedunculated colonic polyps at the ascending and the transverse colon, and numerous variable-sized sessile polyps were scattered all over the colon. To establish hemostasis, endoscopic polypectomy for pedunculated polyps and argon plasma photocoagulation for the bleeding sessile polyps were performed. Histopathological examination revealed cecal adenocarcinoma in one specimen and two simultaneous in situ carcinoma at the transverse and the sigmoid colon in the mucosae of the excised histologically proven hamartomatous polyps. Additionally, one focal in situ carcinoma in the resected colon was detected.Conclusions: When considering the family history, serious GI neoplastic lesions may be unmasked in young patients with PJS who present with hematochezia, even in the absence of its characteristic mucocutaneous pigmented lesions. GI endoscopic surveillance programs should be adopted for diagnosed cases of PJS and their families. Genetic prenatal screening for early detection is the best option for

  1. Thermostable direct hemolysin downregulates human colon carcinoma cell proliferation with the involvement of E-cadherin, and β-catenin/Tcf-4 signaling.

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    Pinki Chowdhury

    Full Text Available BACKGROUND: Colon cancers are the frequent causes of cancer mortality worldwide. Recently bacterial toxins have received marked attention as promising approaches in the treatment of colon cancer. Thermostable direct hemolysin (TDH secreted by Vibrio parahaemolyticus causes influx of extracellular calcium with the subsequent rise in intracellular calcium level in intestinal epithelial cells and it is known that calcium has antiproliferative activity against colon cancer. KEY RESULTS: In the present study it has been shown that TDH, a well-known traditional virulent factor inhibits proliferation of human colon carcinoma cells through the involvement of CaSR in its mechanism. TDH treatment does not induce DNA fragmentation, nor causes the release of lactate dehydrogenase. Therefore, apoptosis and cytotoxicity are not contributing to the TDH-mediated reduction of proliferation rate, and hence the reduction appears to be caused by decrease in cell proliferation. The elevation of E-cadherin, a cell adhesion molecule and suppression of β-catenin, a proto-oncogene have been observed in presence of CaSR agonists whereas reverse effect has been seen in presence of CaSR antagonist as well as si-RNA in TDH treated cells. TDH also triggers a significant reduction of Cyclin-D and cdk2, two important cell cycle regulatory proteins along with an up regulation of cell cycle inhibitory protein p27(Kip1 in presence of CaSR agonists. CONCLUSION: Therefore TDH can downregulate colonic carcinoma cell proliferation and involves CaSR in its mechanism of action. The downregulation occurs mainly through the involvement of E-cadherin-β-catenin mediated pathway and the inhibition of cell cycle regulators as well as upregulation of cell cycle inhibitors.

  2. Enhanced antitumor activity of irofulven in combination with 5-fluorouracil and cisplatin in human colon and ovarian carcinoma cells.

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    Poindessous, Virginie; Koeppel, Florence; Raymond, Eric; Cvitkovic, Esteban; Waters, Stephen J; Larsen, Annette K

    2003-11-01

    Irofulven (6-hydroxymethylacylfulvene, MGI-114, NSC 683863) is a semisynthetic derivative of illudin S, a natural product obtained from the Omphalotus mushroom. Irofulven has demonstrated potent activity against a broad range of solid tumors in both cellular and xenograft models and has shown promising activity in clinical trials. To guide the clinical use of irofulven, the present study used the MTT viability assay to examine the cytotoxic effects obtained by combining irofulven with two other anticancer agents: cisplatin and 5-fluorouracil (5-FU). The study was carried out with HT-29 and HCT-116 colorectal and A2780 ovarian carcinoma cells as well as with their irofulven- (HT-29/IF2, HCT-116/IF27) or cisplatin-resistant (A2780/CP70) variants. The combinations showed strong sequence specificity. Simultaneous exposure to cisplatin and irofulven was at least additive for four cell lines including the cisplatin-resistant A2780/CP70 ovarian cells which exhibit a multifactorial resistance phenotype. Cisplatin followed by irofulven was additive for parental HCT-116 and A2780 cells whereas irofulven followed by cisplatin was antagonistic in all cellular models. Simultaneous exposure to 5-FU and irofulven was at least additive for all six cell lines. 5-FU followed by irofulven was additive for the parental HT-29 and A2780 cells and synergistic for the irofulven-resistant HCT-116 cell line. Irofulven followed by 5-FU was synergistic for the two ovarian cell lines and additive for the two parental colon cell lines. These studies demonstrate that simultaneous exposure to irofulven and cisplatin is at least additive for most cell lines whereas simultaneous exposure to irofulven and 5-FU is additive to synergistic for all the cell lines tested, including the irofulven- and cisplatin-resistant variants. The enhanced cytotoxicity of irofulven in combination with cisplatin and 5-FU support the clinical application of these regimens.

  3. In vivo migration of labeled autologous natural killer cells to liver metastases in patients with colon carcinoma

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    Satolli Maria A

    2006-11-01

    Full Text Available Abstract Background Besides being the effectors of native anti-tumor cytotoxicity, NK cells participate in T-lymphocyte responses by promoting the maturation of dendritic cells (DC. Adherent NK (A-NK cells constitute a subset of IL-2-stimulated NK cells which show increased expression of integrins and the ability to adhere to solid surface and to migrate, infiltrate, and destroy cancer. A critical issue in therapy of metastatic disease is the optimization of NK cell migration to tumor tissues and their persistence therein. This study compares localization to liver metastases of autologous A-NK cells administered via the systemic (intravenous, i.v. versus locoregional (intraarterial, i.a. routes. Patients and methods A-NK cells expanded ex-vivo with IL-2 and labeled with 111In-oxine were injected i.a. in the liver of three colon carcinoma patients. After 30 days, each patient had a new preparation of 111In-A-NK cells injected i.v. Migration of these cells to various organs was evaluated by SPET and their differential localization to normal and neoplastic liver was demonstrated after i.v. injection of 99mTc-phytate. Results A-NK cells expressed a donor-dependent CD56+CD16+CD3- (NK or CD56+CD16+CD3+ (NKT phenotype. When injected i.v., these cells localized to the lung before being visible in the spleen and liver. By contrast, localization of i.a. injected A-NK cells was virtually confined to the spleen and liver. Binding of A-NK cells to liver neoplastic tissues was observed only after i.a. injections. Conclusion This unique study design demonstrates that A-NK cells adoptively transferred to the liver via the intraarterial route have preferential access and substantial accumulation to the tumor site.

  4. Caveolin-1-mediated post-transcriptional regulation of inducible nitric oxide synthase in human colon carcinoma cells

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    EMANUELA FELLEY-BOSCO

    2002-01-01

    Full Text Available Reactive oxygen species are now widely recognized as important players contributing both to cell homeostasis and the development of disease. In this respect nitric oxide (NO is no exception. The discussion here will center on regulation of the inducible form of nitric oxide synthase (iNOS for two reasons. First, only iNOS produces micromolar NO concentrations, amounts that are high by comparison with the picomolar to nanomolar concentrations resulting from Ca2+-controlled NO production by endothelial eNOS or neuronal nNOS. Second, iNOS is not constitutively expressed in cells and regulation of this isoenzyme, in contrast to endothelial eNOS or neuronal nNOS, is widely considered to occur at the transcriptional level only. In particular, we were interested in the possibility that caveolin-1, a protein that functions as a tumor suppressor in colon carcinoma cells (Bender et al., 2002; this issue, might regulate iNOS activity. Our results provide evidence for the existence of a post-transcriptional mechanism controlling iNOS protein levels that involves caveolin-1-dependent sequestration of iNOS within a detergent-insoluble compartment. Interestingly, despite the high degree of conservation of the caveolin-1 scaffolding domain binding motif within all NOS enzymes, the interaction detected between caveolin-1 and iNOS in vitro is crucially dependent on presence of a caveolin-1 sequence element immediately adjacent to the scaffolding domain. A model is presented summarizing the salient aspects of these results. These observations are important in the context of tumor biology, since down-regulation of caveolin-1 is predicted to promote uncontrolled iNOS activity, genotoxic damage and thereby facilitate tumor development in humans

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

    Directory of Open Access Journals (Sweden)

    Chih-Ping Hsu

    2012-01-01

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

  6. Evaluating the effect of four extracts of avocado fruit on esophageal squamous carcinoma and colon adenocarcinoma cell lines in comparison with peripheral blood mononuclear cells.

    Science.gov (United States)

    Vahedi Larijani, Laleh; Ghasemi, Maryam; AbedianKenari, Saeid; Naghshvar, Farshad

    2014-01-01

    Most patients with gastrointestinal cancers refer to the health centers at advanced stages of the disease and conventional treatments are not significantly effective for these patients. Therefore, using modern therapeutic approaches with lower toxicity bring higher chance for successful treatment and reduced adverse effects in such patients. The aim of this study is to evaluate the effect of avocado fruit extracts on inhibition of the growth of cancer cells in comparison with normal cells. In an experimental study, ethanol, chloroform, ethyl acetate, and petroleum extracts of avocado (Persea americana) fruit were prepared. Then, the effects if the extracts on the growth of esophageal squamous cell carcinoma and colon adenocarcinoma cell lines were evaluated in comparison with the control group using the MTT test in the cell culture medium. Effects of the four extracts of avocado fruit on three cells lines of peripheral blood mononuclear cells, esophageal squamous cell carcinoma, and colon adenocarcinoma were tested. The results showed that avocado fruit extract is effective in inhibition of cancer cell growth in comparison with normal cells (PAvocado fruit is rich in phytochemicals, which play an important role in inhibition of growth of cancer cells. The current study for the first time demonstrates the anti-cancer effect of avocado fruit extracts on two cancers common in Iran. Therefore, it is suggested that the fruit extracts can be considered as appropriate complementary treatments in treatment of esophageal and colon cancers.

  7. Continuous blood pressure monitoring via non-invasive radial artery applanation tonometry and invasive arterial catheter demonstrates good agreement in patients undergoing colon carcinoma surgery.

    Science.gov (United States)

    Sun, Jing; Chen, Hanjian; Zheng, Jun; Mao, Bin; Zhu, Shengmei; Feng, Jingyi

    2017-12-01

    Radial artery applanation tonometry (RAAT) has been developed and utilized for continuous arterial pressure monitoring. However, evidence is lacking to clinically verify the RAAT technology and identify appropriate patient groups before routine clinical use. This study aims to evaluate the RAAT technology by comparing systolic blood pressure (SBP), mean blood pressure (MBP) and diastolic blood pressure (DBP) values in patients undergoing colon carcinoma surgery. Blood Pressure (BP) values obtained via RAAT (TL-300, Tensys Medical Inc., San Diego, CA, USA) and conventional arterial catheterization from 30 colon carcinoma surgical patients were collected and compared via Bland-Atman method, linear regression and 4-quadrant plot concordance analysis. For SBPs, MBPs and DBPs, means of the differences (±standard deviation; 95% limits of agreement) were -0.9 (±7.6; -15.7 to 13.9) mmHg, 3.1 (±6.5; -9.6 to 15.8) mmHg and 4.3 (±7.4; -10.3 to 18.8) mmHg, respectively. Linear regression coefficients of determination were 0.8706 for SBPs, 0.8353 for MBPs and 0.6858 for DBPs. Four-quadrant concordance correlation coefficients were 0.8740, 0.8522 and 0.7108 for SBPs, MBPs and DBPs, respectively. A highly selected patient collective undergoing colon carcinoma surgery was studied. BP measurements obtained via the TL-300 had clinically acceptable agreement with that acquired invasively using an arterial catheter. For use in clinical routine, it is necessary to take measures for improvement regarding movement artifacts and dilution of noise. A large sample size of patients under various conditions is also needed to further evaluate the RAAT technology before clinically routine use.

  8. Metastasis-associated in colon cancer 1 is a novel survival-related biomarker for human patients with renal pelvis carcinoma.

    Directory of Open Access Journals (Sweden)

    Hailong Hu

    Full Text Available Metastasis-associated in colon cancer 1 (MACC1 has recently been identified as a novel independent prognostic indicator for metastasis occurrence, overall survival and cancer-free survival for patients with colon cancer and other solid tumors. In this study, we investigated the role of MACC1 in the development and progression of renal pelvis carcinoma, a form of upper tract urothelial carcinomas. MACC1 protein has been found in the cytoplasm as well as in the nucleus of the transitional epithelial cells of the normal renal pelvis in immunohistochemical (IHC assays. Quantitative IHC examinations revealed that MACC1 abnormal abundance in cancerous tissues might represent a biological indicator clinically suggestive of tumor malignancy in the renal pelvis. Furthermore, investigation of the association of MACC1 protein levels with clinicopathological parameters in this study has suggested a correlation of MACC1 expression with tumor-node-metastasis stage and histopathological grade of patients with renal pelvis carcinoma, with elevated MACC1 protein levels frequently associated with higher aggressiveness of the disease. Moreover, both disease-free survival and overall survival for the patients in the high MACC1 expression group were significantly lower than those in the low expression group. Multivariate analysis with a Cox proportional-hazards model suggested that MACC1 is indeed an independent prognostic indicator of overall survival and cancer-free survival for patients with renal pelvis carcinoma. Thus, MACC1 may represent a promising prognostic biomarker candidate, as well as a potential therapeutic target for this disease.

  9. Lactobacillus casei Exerts Anti-Proliferative Effects Accompanied by Apoptotic Cell Death and Up-Regulation of TRAIL in Colon Carcinoma Cells.

    Science.gov (United States)

    Tiptiri-Kourpeti, Angeliki; Spyridopoulou, Katerina; Santarmaki, Valentina; Aindelis, Georgios; Tompoulidou, Evgenia; Lamprianidou, Eleftheria E; Saxami, Georgia; Ypsilantis, Petros; Lampri, Evangeli S; Simopoulos, Constantinos; Kotsianidis, Ioannis; Galanis, Alex; Kourkoutas, Yiannis; Dimitrellou, Dimitra; Chlichlia, Katerina

    2016-01-01

    Probiotic microorganisms such as lactic acid bacteria (LAB) exert a number of strain-specific health-promoting activities attributed to their immunomodulatory, anti-inflammatory and anti-carcinogenic properties. Despite recent attention, our understanding of the biological processes involved in the beneficial effects of LAB strains is still limited. To this end, the present study investigated the growth-inhibitory effects of Lactobacillus casei ATCC 393 against experimental colon cancer. Administration of live Lactobacillus casei (as well as bacterial components thereof) on murine (CT26) and human (HT29) colon carcinoma cell lines raised a significant concentration- and time-dependent anti-proliferative effect, determined by cell viability assays. Specifically, a dramatic decrease in viability of colon cancer cells co-incubated with 10(9) CFU/mL L. casei for 24 hours was detected (78% for HT29 and 52% for CT26 cells). In addition, live L. casei induced apoptotic cell death in both cell lines as revealed by annexin V and propidium iodide staining. The significance of the in vitro anti-proliferative effects was further confirmed in an experimental tumor model. Oral daily administration of 10(9) CFU live L. casei for 13 days significantly inhibited in vivo growth of colon carcinoma cells, resulting in approximately 80% reduction in tumor volume of treated mice. Tumor growth inhibition was accompanied by L. casei-driven up-regulation of the TNF-related apoptosis-inducing ligand TRAIL and down-regulation of Survivin. Taken together, these findings provide evidence for beneficial tumor-inhibitory, anti-proliferative and pro-apoptotic effects driven by this probiotic LAB strain.

  10. Lactobacillus casei Exerts Anti-Proliferative Effects Accompanied by Apoptotic Cell Death and Up-Regulation of TRAIL in Colon Carcinoma Cells.

    Directory of Open Access Journals (Sweden)

    Angeliki Tiptiri-Kourpeti

    Full Text Available Probiotic microorganisms such as lactic acid bacteria (LAB exert a number of strain-specific health-promoting activities attributed to their immunomodulatory, anti-inflammatory and anti-carcinogenic properties. Despite recent attention, our understanding of the biological processes involved in the beneficial effects of LAB strains is still limited. To this end, the present study investigated the growth-inhibitory effects of Lactobacillus casei ATCC 393 against experimental colon cancer. Administration of live Lactobacillus casei (as well as bacterial components thereof on murine (CT26 and human (HT29 colon carcinoma cell lines raised a significant concentration- and time-dependent anti-proliferative effect, determined by cell viability assays. Specifically, a dramatic decrease in viability of colon cancer cells co-incubated with 10(9 CFU/mL L. casei for 24 hours was detected (78% for HT29 and 52% for CT26 cells. In addition, live L. casei induced apoptotic cell death in both cell lines as revealed by annexin V and propidium iodide staining. The significance of the in vitro anti-proliferative effects was further confirmed in an experimental tumor model. Oral daily administration of 10(9 CFU live L. casei for 13 days significantly inhibited in vivo growth of colon carcinoma cells, resulting in approximately 80% reduction in tumor volume of treated mice. Tumor growth inhibition was accompanied by L. casei-driven up-regulation of the TNF-related apoptosis-inducing ligand TRAIL and down-regulation of Survivin. Taken together, these findings provide evidence for beneficial tumor-inhibitory, anti-proliferative and pro-apoptotic effects driven by this probiotic LAB strain.

  11. Lactobacillus casei Exerts Anti-Proliferative Effects Accompanied by Apoptotic Cell Death and Up-Regulation of TRAIL in Colon Carcinoma Cells

    Science.gov (United States)

    Santarmaki, Valentina; Aindelis, Georgios; Tompoulidou, Evgenia; Lamprianidou, Eleftheria E.; Saxami, Georgia; Ypsilantis, Petros; Lampri, Evangeli S.; Simopoulos, Constantinos; Kotsianidis, Ioannis; Galanis, Alex; Kourkoutas, Yiannis; Dimitrellou, Dimitra; Chlichlia, Katerina

    2016-01-01

    Probiotic microorganisms such as lactic acid bacteria (LAB) exert a number of strain-specific health-promoting activities attributed to their immunomodulatory, anti-inflammatory and anti-carcinogenic properties. Despite recent attention, our understanding of the biological processes involved in the beneficial effects of LAB strains is still limited. To this end, the present study investigated the growth-inhibitory effects of Lactobacillus casei ATCC 393 against experimental colon cancer. Administration of live Lactobacillus casei (as well as bacterial components thereof) on murine (CT26) and human (HT29) colon carcinoma cell lines raised a significant concentration- and time-dependent anti-proliferative effect, determined by cell viability assays. Specifically, a dramatic decrease in viability of colon cancer cells co-incubated with 109 CFU/mL L. casei for 24 hours was detected (78% for HT29 and 52% for CT26 cells). In addition, live L. casei induced apoptotic cell death in both cell lines as revealed by annexin V and propidium iodide staining. The significance of the in vitro anti-proliferative effects was further confirmed in an experimental tumor model. Oral daily administration of 109 CFU live L. casei for 13 days significantly inhibited in vivo growth of colon carcinoma cells, resulting in approximately 80% reduction in tumor volume of treated mice. Tumor growth inhibition was accompanied by L. casei-driven up-regulation of the TNF-related apoptosis-inducing ligand TRAIL and down-regulation of Survivin. Taken together, these findings provide evidence for beneficial tumor-inhibitory, anti-proliferative and pro-apoptotic effects driven by this probiotic LAB strain. PMID:26849051

  12. Depletion of mitochondrial fission factor DRP1 causes increased apoptosis in human colon cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Inoue-Yamauchi, Akane, E-mail: ainoyama@research.twmu.ac.jp [Department of Pathology, Tokyo Women' s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666 (Japan); Oda, Hideaki [Department of Pathology, Tokyo Women' s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666 (Japan)

    2012-04-27

    Highlights: Black-Right-Pointing-Pointer DRP1 is required for mitochondrial fission in colon cancer cells. Black-Right-Pointing-Pointer DRP1 participates in inhibition of colon cancer cell apoptosis. Black-Right-Pointing-Pointer DRP1 can inhibit apoptosis through the regulation of cytochrome c release. -- Abstract: Mitochondria play a critical role in regulation of apoptosis, a form of programmed cell death, by releasing apoptogenic factors including cytochrome c. Growing evidence suggests that dynamic changes in mitochondrial morphology are involved in cellular apoptotic response. However, whether DRP1-mediated mitochondrial fission is required for induction of apoptosis remains speculative. Here, we show that siRNA-mediated DRP1 knockdown promoted accumulation of elongated mitochondria in HCT116 and SW480 human colon cancer cells. Surprisingly, DRP1 down-regulation led to decreased proliferation and increased apoptosis of these cells. A higher rate of cytochrome c release and reductions in mitochondrial membrane potential were also revealed in DRP1-depleted cells. Taken together, our present findings suggest that mitochondrial fission factor DRP1 inhibits colon cancer cell apoptosis through the regulation of cytochrome c release and mitochondrial membrane integrity.

  13. Comparison of intracellular accumulation and cytotoxicity of free mTHPC and mTHPC-loaded PLGA nanoparticles in human colon carcinoma cells

    Science.gov (United States)

    Löw, Karin; Knobloch, Thomas; Wagner, Sylvia; Wiehe, Arno; Engel, Andrea; Langer, Klaus; von Briesen, Hagen

    2011-06-01

    The second generation photosensitizer mTHPC was approved by the European Medicines Agency (EMA) for the palliative treatment of advanced head and neck cancer in October 2001. It is known that mTHPC possesses a significant phototoxicity against a variety of human cancer cells in vitro but also exhibits dark toxicity and can cause adverse effects (especially skin photosensitization). Due to its poor water solubility, the administration of hydrophobic photosensitizer still presents several difficulties. To overcome the administration problems, the use of nanoparticles as drug carrier systems is much investigated. Nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) have been extensively studied as delivery systems into tumours due to their biocompatibility and biodegradability. The goal of this study was the comparison of free mTHPC and mTHPC-loaded PLGA nanoparticles concerning cytotoxicity and intracellular accumulation in human colon carcinoma cells (HT29). The nanoparticles delivered the photosensitizer to the colon carcinoma cells and enabled drug release without losing its activity. The cytotoxicity assays showed a time- and concentration-dependent decrease in cell proliferation and viability after illumination. However, first and foremost mTHPC lost its dark toxic effects using the PLGA nanoparticles as a drug carrier system. Therefore, PLGA nanoparticles are a promising drug carrier system for the hydrophobic photosensitizer mTHPC.

  14. Anticarcinogenic effects of polyphenolics from mango (Mangifera indica) varieties.

    Science.gov (United States)

    Noratto, Giuliana D; Bertoldi, Michele C; Krenek, Kimberley; Talcott, Stephen T; Stringheta, Paulo C; Mertens-Talcott, Susanne U

    2010-04-14

    Many polyphenolics contained in mango have shown anticancer activity. The objective of this study was to compare the anticancer properties of polyphenolic extracts from several mango varieties (Francis, Kent, Ataulfo, Tommy Atkins, and Haden) in cancer cell lines, including Molt-4 leukemia, A-549 lung, MDA-MB-231 breast, LnCap prostate, and SW-480 colon cancer cells and the noncancer colon cell line CCD-18Co. Cell lines were incubated with Ataulfo and Haden extracts, selected on the basis of their superior antioxidant capacity compared to the other varieties, where SW-480 and MOLT-4 were statistically equally most sensitive to both cultivars followed by MDA-MB-231, A-549, and LnCap in order of decreasing efficacy as determined by cell counting. The efficacy of extracts from all mango varieties in the inhibition of cell growth was tested in SW-480 colon carcinoma cells, where Ataulfo and Haden demonstrated superior efficacy, followed by Kent, Francis, and Tommy Atkins. At 5 mg of GAE/L, Ataulfo inhibited the growth of colon SW-480 cancer cells by approximately 72% while the growth of noncancer colonic myofibroblast CCD-18Co cells was not inhibited. The growth inhibition exerted by Ataulfo and Haden polyphenolics in SW-480 was associated with an increased mRNA expression of pro-apoptotic biomarkers and cell cycle regulators, cell cycle arrest, and a decrease in the generation of reactive oxygen species. Overall, polyphenolics from several mango varieties exerted anticancer effects, where compounds from Haden and Ataulfo mango varieties possessed superior chemopreventive activity.

  15. p53 Over-expression and p53 mutations in colon carcinomas: Relation to dietary risk factors

    NARCIS (Netherlands)

    Voskuil, D.W.; Kampman, E.; Kraats, A.A. van; Balder, H.F.; Muijen, G.N.P. van; Goldbohm, R.A.; Veer, P. van 't

    1999-01-01

    Epidemiological studies have suggested that dietary factors may differently affect p53-dependent and p53-independent pathways to colon cancer. Results of such studies may depend on the method used to assess p53 status. This case-control study of 185 colon-cancer cases and 259 controls examines this

  16. The Carcinoma–Stromal Ratio of Colon Carcinoma Is an Independent Factor for Survival Compared to Lymph Node Status and Tumor Stage

    Directory of Open Access Journals (Sweden)

    Wilma E. Mesker

    2007-01-01

    Full Text Available Background: Tumor staging insufficiently discriminates between colon cancer patients with poor and better prognosis. We have evaluated, for the primary tumor, if the carcinoma-percentage (CP, as a derivative from the carcinoma-stromal ratio, can be applied as a candidate marker to identify patients for adjuvant therapy. Methods: In a retrospective study of 63 patients with colon cancer (stage I–III, 1990–2001 the carcinoma-percentage of the primary tumor was estimated on routine H&E stained histological sections. Additionally these findings were validated in a second independent study of 59 patients (stage I–III, 1980–1992. (None of the patients had received preoperative chemo- or radiation therapy nor adjuvant chemotherapy. Results: Of 122 analyzed patients 33 (27.0% had a low CP and 89 (73.0% a high CP. The analysis of mean survival revealed: overall-survival (OS 2.13 years, disease-free- survival (DFS 1.51 years for CP-low and OS 7.36 years, DFS 6.89 years for CP-high. Five-year survival rates for CP-low versus CP-high were respectively for OS: 15.2% and 73.0% and for DFS: 12.1% and 67.4%. High levels of significance were found (OS p < 0.0001, DFS p < 0.0001 with hazard ratio’s of 3.73 and 4.18. In a multivariate Cox regression analysis, CP remained an independent variable when adjusted for either stage or for tumor status and lymph-node status (OSp < 0.001, OSp < 0.001. Conclusions: The carcinoma-percentage in primary colon cancer is a factor to discriminate between patients with a poor and a better outcome of disease. This parameter is already available upon routine histological investigation and can, in addition to the TNM classification, be a candidate marker to further stratify into more individual risk groups.

  17. Differential roles of Hath1, MUC2 and P27Kip1 in relation with gamma-secretase inhibition in human colonic carcinomas: a translational study.

    Directory of Open Access Journals (Sweden)

    Frédérique Souazé

    Full Text Available Hath1, a bHLH transcription factor negatively regulated by the γ-secretase-dependent Notch pathway, is required for intestinal secretory cell differentiation. Our aim was fourfold: 1 determine whether Hath1 is able to alter the phenotype of colon cancer cells that are committed to a differentiated phenotype, 2 determine whether the Hath1-dependent alteration of differentiation is coupled to a restriction of anchorage-dependent growth, 3 decipher the respective roles of three putative tumor suppressor genes Hath1, MUC2 and P27kip1 in this coupling and, 4 examine how our findings translate to primary tumors. Human colon carcinoma cell lines that differentiate along a mucin secreting (MUC2/MUC5AC and/or enterocytic (DPPIV lineages were maintained on inserts with or without a γ-secretase inhibitor (DBZ. Then the cells were detached and their ability to survive/proliferate in the absence of substratum was assessed. γ-secretase inhibition led to a Hath1-mediated preferential induction of MUC2 over MUC5AC, without DPPIV modification, in association with a decrease in anchorage-independent growth. While P27kip1 silencing relieved the cells from the Hath1-induced decrease of anchorage-independent growth, MUC2 silencing did not modify this parameter. Hath1 ectopic expression in the Hath1 negative enterocytic Caco2 cells led to a decreased anchorage-independent growth in a P27kip1-independent manner. In cultured primary human colon carcinomas, Hath1 was up-regulated in 7 out of 10 tumors upon DBZ treatment. Parallel MUC2 up-regulation occurred in 4 (4/7 and P27kip1 in only 2 (2/7 tumors. Interestingly, the response patterns of primary tumors to DBZ fitted with the hierarchical model of divergent signalling derived from our findings on cell lines.

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

    Directory of Open Access Journals (Sweden)

    Stefania Meschini

    2017-09-01

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

  19. Mucinous adenocarcinoma of colon

    National Research Council Canada - National Science Library

    Zamir, Naima; Ahmed, Soofia; Akhtar, Jamshed

    2010-01-01

    .... Underlying colorectal carcinoma is a rare cause and carries a poor prognosis. We report two cases of mucinous adenocarcinoma of colon, one in a 9 years old male and other in a female of 12 years...

  20. Stem cell carcinoma of the colon and rectum. Report of two cases and review of the literature

    DEFF Research Database (Denmark)

    Palvio, D H; Sørensen, Flemming Brandt; Kløve-Mogensen, M

    1985-01-01

    Two cases of highly malignant tumors, one originating in the sigmoid colon and the other in the rectum, are presented. Both tumors showed light microscopic, electron microscopic, and immunohistochemical evidence of multidirectional differentiation. The tumors were composed mainly of undifferentia...

  1. Gadopentetate dimeglumine versus ultrasmall superparamagnetic iron oxide for dynamic contrast-enhanced MR imaging of tumor angiogenesis in human colon carcinoma in mice.

    Science.gov (United States)

    de Lussanet, Quido G; Backes, Walter H; Griffioen, Arjan W; van Engelshoven, Jos M A; Beets-Tan, Regina G H

    2003-11-01

    To compare the kinetic physiologic properties of a clinical contrast agent, gadopentetate dimeglumine, with those of ultrasmall superparamagnetic iron oxide (USPIO) particles for dynamic contrast material-enhanced magnetic resonance (MR) imaging of tumor angiogenesis in human colon carcinoma in mice with a clinical MR imaging unit. Thirty-two mice with human colon carcinoma were injected with either gadopentetate dimeglumine (n = 16) or USPIO (n = 16) for dynamic contrast-enhanced MR imaging and pre- and postcontrast T2 and T2* measurements. Dynamic contrast-enhanced MR imaging measurements were analyzed by using a two-compartment model to calculate the endothelial transfer coefficient surface area product (KPS) for the tumor microvasculature, the reflux coefficient (k), and the fractional plasma volume (fPV). KPS, k, and fPV maps were compared with histologic microvessel density (MVD) and used to observe differences between core and rim regions of tumor. Results in 30 mice (15 in the gadopentetate dimeglumine group and 15 in the USPIO group) could be used. KPS values measured with both agents correlated well with MVD in hot spots (gadopentetate dimeglumine: r = 0.6, P =.02; USPIO: r = 0.6, P =.01). No significant difference (P =.4) in correlation was found between the two agents. Both USPIO and gadopentetate dimeglumine demonstrated higher MVD and KPS values in tumor rim than in tumor core (P gadopentetate dimeglumine (r = 0.3, P =.4) and USPIO (r = 0.2, P =.6), while fPV values correlated well with whole-tumor MVD for USPIO (r = 0.6, P =.02) but not gadopentetate dimeglumine (r = -0.01, P =.98). T2 and T2* measurements showed small differences between areas of high and low angiogenic activity with both agents. The kinetic physiologic properties of gadopentetate dimeglumine are as good as those of USPIO for dynamic contrast-enhanced MR imaging for calculating KPS as a measurement of angiogenesis in human colon carcinoma. Further studies with patients may reveal

  2. Converging signals synergistically activate the LAMC2 promoter and lead to accumulation of the laminin gamma 2 chain in human colon carcinoma cells

    DEFF Research Database (Denmark)

    Olsen, Jørgen; Kirkeby, Lene T; Brorsson, Marianne M

    2003-01-01

    The trimeric extracellular matrix molecule laminin-5 and its constituent chains (alpha 3, beta 3, gamma 2) are normally not detectable intracellularly in intestinal epithelial cells but the laminin gamma 2 chain can be detected in cancer cells at the invasive front of a subset of colon carcinomas....... These cells are subjected to cytokines such as transforming growth factor beta 1 (TGF-beta 1) and hepatocyte growth factor (HGF), produced by the tumour cells or by the surrounding stromal cells. The purpose of the present work was to investigate whether TGF-beta 1 and HGF, known to stimulate the LAMC2 gene...... encoding the laminin gamma 2 chain, might synergize to activate the LAMC2 promoter, and to identify the promoter elements involved. We find evidence for synergy between TGF-beta and HGF with respect to laminin gamma 2 chain expression and promoter activation and demonstrate that this requires the 5...

  3. STI571 reduces TRAIL-induced apoptosis in colon cancer cells: c-Abl activation by the death receptor leads to stress kinase-dependent cell death

    Directory of Open Access Journals (Sweden)

    Huang Duen-Yi

    2012-03-01

    Full Text Available Abstract Background In an effort to achieve better cancer therapies, we elucidated the combination cancer therapy of STI571 (an inhibitor of Bcr-Abl and clinically used for chronic myelogenous leukemia and TNF-related apoptosis-inducing ligand (TRAIL, a developing antitumor agent in leukemia, colon, and prostate cancer cells. Methods Colon cancer (HCT116, SW480, prostate cancer (PC3, LNCaP and leukemia (K562 cells were treated with STI571 and TRAIL. Cell viability was determined by MTT assay and sub-G1 appearance. Protein expression and kinase phosphorylation were determined by Western blotting. c-Abl and p73 activities were inhibited by target-specific small interfering (siRNA. In vitro kinase assay of c-Abl was conducted using CRK as a substrate. Results We found that STI571 exerts opposite effects on the antitumor activity of TRAIL. It enhanced cytotoxicity in TRAIL-treated K562 leukemia cells and reduced TRAIL-induced apoptosis in HCT116 and SW480 colon cancer cells, while having no effect on PC3 and LNCaP cells. In colon and prostate cancer cells, TRAIL caused c-Abl cleavage to the active form via a caspase pathway. Interestingly, JNK and p38 MAPK inhibitors effectively blocked TRAIL-induced toxicity in the colon, but not in prostate cancer cells. Next, we found that STI571 could attenuate TRAIL-induced c-Abl, JNK and p38 activation in HCT116 cells. In addition, siRNA targeting knockdown of c-Abl and p73 also reduced TRAIL-induced cytotoxicity, rendering HCT116 cells less responsive to stress kinase activation, and masking the cytoprotective effect of STI571. Conclusions All together we demonstrate a novel mediator role of p73 in activating the stress kinases p38 and JNK in the classical apoptotic pathway of TRAIL. TRAIL via caspase-dependent action can sequentially activate c-Abl, p73, and stress kinases, which contribute to apoptosis in colon cancer cells. Through the inhibition of c-Abl-mediated apoptotic p73 signaling, STI571 reduces

  4. Infectious endocarditis from Streptococcus bovis associated with colonic carcinoma: case report and literature review Endocardite infecciosa por Streptococcus bovis associada com carcinoma cólico: relato de caso e revisão da literatura

    Directory of Open Access Journals (Sweden)

    Jaques Waisberg

    2002-07-01

    Full Text Available BACKGROUND: Many studies in the literature have warned of the need for investigation of colonic lesions among patients, especially elderly ones, who have bacteremia and/or endocarditis from Streptococcus bovis. Bacteremia and infectious endocarditis from Streptococcus bovis may be related to the presence of neoplastic lesions in the large intestine and hepatic disease. AIM: This report describes a patient who presented infectious endocarditis from Streptococcus bovis associated with colonic carcinoma and tubular-villous adenomas. CONCLUSIONS: The finding of this bacterium among patients with septicemia and/or endocarditis is also related to the presence of villous or tubular-villous adenomas in the large intestine. For this reason, complete and detailed investigation of the large intestine must be performed in patients with infectious endocarditis, even in the absence of intestinal symptoms. An increased incidence of this condition or hepatic dysfunction has been reported among patients with infectious endocarditis from Streptococcus bovis. Patients with infectious endocarditis from Streptococcus bovis and normal colonoscopy may be included in the group at risk for developing colonic cancer. The knowledge that there is an association between endocarditis from Streptococcus bovis and carcinoma of the colon has important clinical implications. If the lesion can be discovered at an early stage, curative resection may become possible.RACIONAL: Diferentes estudos na literatura têm alertado para a necessidade de investigação de lesões cólicas entre doentes, especialmente nos mais idosos, que apresentem bacteremia e/ou endocardite por Streptococcus bovis. A bacteremia e a endocardite infecciosa por S. bovis pode estar relacionada à presença de lesões neoplásicas do intestino grosso e a doença hepática. OBJETIVO: Descrição do caso de doente com endocardite infecciosa por S. bovis associada a carcinoma cólico e adenomas t

  5. Drug-loading of poly(ethylene glycol methyl ether methacrylate) (PEGMEMA)-based micelles and mechanisms of uptake in colon carcinoma cells.

    Science.gov (United States)

    Chang, Teddy; Gosain, Pallavi; Stenzel, Martina H; Lord, Megan S

    2016-08-01

    In this study polymeric micelles formed from poly(poly(ethylene glycol) methyl ether methacrylate)-block-poly(methyl methacrylate) (P(PEGMEMA75)-b-PMMA80) block copolymer of approximately 25nm in diameter were used to encapsulate the model drug, Nile Red, with a loading efficiency of 0.08wt% and a chemotherapeutic drug, doxorubicin (DOX), with an efficiency of 2.75wt%. The release of DOX from the micelles was sufficient to be cytotoxic to human colon carcinoma cells, WiDr, while Nile Red and the unloaded micelles were found not to be cytotoxic when exposed to the cells at polymer concentrations up to 200μg/mL. Nile Red loaded micelles were used to analyze uptake of the micelles into the cells which were rapidly internalized within minutes of exposure. The three major endocytotic pathways were involved in the internalization of micelles; however other passive mechanisms were also at play as the addition of inhibitors to all three pathways did not completely inhibit the uptake of these nanoparticles. These data demonstrate the potential of the P(PEGMEMA)75-b-PMMA80 block copolymer micelles to be rapidly internalized by carcinoma cells and deliver low doses of drugs intracellularly for controlled drug release. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

  6. Loss of WNT-TCF addiction and enhancement of HH-GLI1 signalling define the metastatic transition of human colon carcinomas.

    Science.gov (United States)

    Varnat, Frédéric; Siegl-Cachedenier, Irene; Malerba, Monica; Gervaz, Pascal; Ruiz i Altaba, Ariel

    2010-11-01

    Previous studies demonstrate the initiation of colon cancers through deregulation of WNT-TCF signalling. An accepted but untested extension of this finding is that incurable metastatic colon carcinomas (CCs) universally remain WNT-TCF-dependent, prompting the search for WNT-TCF inhibitors. CCs and their stem cells also require Hedgehog (HH)-GLI1 activity, but how these pathways interact is unclear. Here we define coincident high-to-low WNT-TCF and low-to-high HH-GLI transitions in patient CCs, most strikingly in their CD133(+) stem cells, that mark the development of metastases. We find that enhanced HH-GLI mimics this transition, driving also an embryonic stem (ES)-like stemness signature and that GLI1 can be regulated by multiple CC oncogenes. The data support a model in which the metastatic transition involves the acquisition or enhancement of a more primitive ES-like phenotype, and the downregulation of the early WNT-TCF programme, driven by oncogene-regulated high GLI1 activity. Consistently, TCF blockade does not generally inhibit tumour growth; instead, it, like enhanced HH-GLI, promotes metastatic growth in vivo. Treatments for metastatic disease should therefore block HH-GLI1 but not WNT-TCF activities.

  7. Increased expression and activity of group IIA and X secretory phospholipase A2 in peritumoral versus central colon carcinoma tissue

    DEFF Research Database (Denmark)

    Tribler, Line; Jensen, Lotte T; Jørgensen, Kent

    2007-01-01

    Secretory phospholipase A2 (sPLA2) type IIA and X was analyzed in tumors from 22 patients with colon adenocarcinomas in order to determine the involvement and activity of sPLA2 in colon cancer. Evaluation of immunoreactive sPLA2 IIA by Western blotting showed a significantly higher level in the p......Secretory phospholipase A2 (sPLA2) type IIA and X was analyzed in tumors from 22 patients with colon adenocarcinomas in order to determine the involvement and activity of sPLA2 in colon cancer. Evaluation of immunoreactive sPLA2 IIA by Western blotting showed a significantly higher level...... in the periphery of the tumors, compared to central tumor regions. Increased levels of sPLA2 IIA protein correlated with a two-fold increase in sPLA2 enzymatic activity in the peripheral regions compared to central regions. Nineteen out of 22 tumors showed high levels of sPLA2 IIA, whereas 7 out of the 22 tumors...

  8. Berberine Reduces cAMP-Induced Chloride Secretion in T84 Human Colonic Carcinoma Cells through Inhibition of Basolateral KCNQ1 Channels.

    LENUS (Irish Health Repository)

    Alzamora, Rodrigo

    2012-02-01

    Berberine is a plant alkaloid with multiple pharmacological actions, including antidiarrhoeal activity and has been shown to inhibit Cl(-) secretion in distal colon. The aims of this study were to determine the molecular signaling mechanisms of action of berberine on Cl(-) secretion and the ion transporter targets. Monolayers of T84 human colonic carcinoma cells grown in permeable supports were placed in Ussing chambers and short-circuit current measured in response to secretagogues and berberine. Whole-cell current recordings were performed in T84 cells using the patch-clamp technique. Berberine decreased forskolin-induced short-circuit current in a concentration-dependent manner (IC(50) 80 +\\/- 8 muM). In apically permeabilized monolayers and whole-cell current recordings, berberine inhibited a cAMP-dependent and chromanol 293B-sensitive basolateral membrane K(+) current by 88%, suggesting inhibition of KCNQ1 K(+) channels. Berberine did not affect either apical Cl(-) conductance or basolateral Na(+)-K(+)-ATPase activity. Berberine stimulated p38 MAPK, PKCalpha and PKA, but had no effect on p42\\/p44 MAPK and PKCdelta. However, berberine pre-treatment prevented stimulation of p42\\/p44 MAPK by epidermal growth factor. The inhibitory effect of berberine on Cl(-) secretion was partially blocked by HBDDE ( approximately 65%), an inhibitor of PKCalpha and to a smaller extent by inhibition of p38 MAPK with SB202190 ( approximately 15%). Berberine treatment induced an increase in association between PKCalpha and PKA with KCNQ1 and produced phosphorylation of the channel. We conclude that berberine exerts its inhibitory effect on colonic Cl(-) secretion through inhibition of basolateral KCNQ1 channels responsible for K(+) recycling via a PKCalpha-dependent pathway.

  9. Berberine Reduces cAMP-Induced Chloride Secretion in T84 Human Colonic Carcinoma Cells through Inhibition of Basolateral KCNQ1 Channels.

    LENUS (Irish Health Repository)

    Alzamora, Rodrigo

    2011-01-01

    Berberine is a plant alkaloid with multiple pharmacological actions, including antidiarrhoeal activity and has been shown to inhibit Cl(-) secretion in distal colon. The aims of this study were to determine the molecular signaling mechanisms of action of berberine on Cl(-) secretion and the ion transporter targets. Monolayers of T84 human colonic carcinoma cells grown in permeable supports were placed in Ussing chambers and short-circuit current measured in response to secretagogues and berberine. Whole-cell current recordings were performed in T84 cells using the patch-clamp technique. Berberine decreased forskolin-induced short-circuit current in a concentration-dependent manner (IC(50) 80 ± 8 μM). In apically permeabilized monolayers and whole-cell current recordings, berberine inhibited a cAMP-dependent and chromanol 293B-sensitive basolateral membrane K(+) current by 88%, suggesting inhibition of KCNQ1 K(+) channels. Berberine did not affect either apical Cl(-) conductance or basolateral Na(+)-K(+)-ATPase activity. Berberine stimulated p38 MAPK, PKCα and PKA, but had no effect on p42\\/p44 MAPK and PKCδ. However, berberine pre-treatment prevented stimulation of p42\\/p44 MAPK by epidermal growth factor. The inhibitory effect of berberine on Cl(-) secretion was partially blocked by HBDDE (∼65%), an inhibitor of PKCα and to a smaller extent by inhibition of p38 MAPK with SB202190 (∼15%). Berberine treatment induced an increase in association between PKCα and PKA with KCNQ1 and produced phosphorylation of the channel. We conclude that berberine exerts its inhibitory effect on colonic Cl(-) secretion through inhibition of basolateral KCNQ1 channels responsible for K(+) recycling via a PKCα-dependent pathway.

  10. Berberine reduces cAMP-induced chloride secretion in T84 human colonic carcinoma cells through inhibition of basolateral KCNQ1 channels

    Directory of Open Access Journals (Sweden)

    Rodrigo eAlzamora

    2011-06-01

    Full Text Available Berberine is a plant alkaloid with multiple pharmacological actions, including antidiarrhoeal activity and has been shown to inhibit Cl- secretion in distal colon. The aims of this study were to determine the molecular signalling mechanisms of action of berberine on Cl- secretion and the ion transporter targets. Monolayers of T84 human colonic carcinoma cells grown in permeable supports were placed in Ussing chambers and short-circuit current measured in response to secretagogues and berberine. Whole-cell current recordings were performed in T84 cells using the patch-clamp technique. Berberine decreased forskolin-induced short-circuit current in a concentration-dependent manner (IC50 80  8 M. In apically permeabilized monolayers and whole-cell current recordings, berberine inhibited a cAMP-dependent and chromanol 293B-sensitive basolateral membrane K+ current by 88%, suggesting inhibition of KCNQ1 K+ channels. Berberine did not affect either apical Cl- conductance or basolateral Na+-K+-ATPase activity. Berberine stimulated p38 MAPK, PKC and PKA, but had no effect on p42/p44 MAPK and PKC. However, berberine pre-treatment prevented stimulation of p42/p44 MAPK by epidermal growth factor. The inhibitory effect of berberine on Cl- secretion was partially blocked by HBDDE (65 %, an inhibitor of PKC and to a smaller extent by inhibition of p38 MAPK with SB202190 (15 %. Berberine treatment induced an increase in association between PKC and PKA with KCNQ1 and produced phosphorylation of the channel. We conclude that berberine exerts its inhibitory effect on colonic Cl- secretion through inhibition of basolateral KCNQ1 channels responsible for K+ recycling via a PKC-dependent pathway.

  11. Estudio de las bases anatómicas del carcinoma de colon en la población juvenil

    OpenAIRE

    Flores Gutiérrez, Juan Pablo

    2013-01-01

    Introducción. Un tercio de los carcinomas colorrectales se presentan en pacientes jóvenes por debajo de los 50 años de edad, el 15% de éstos se relacionan con inestabilidad microsatelital debida a mutaciones en la línea germinal de los genes relacionados con la reparación del ADN. La otra proporción de carcinomas colorrectales tienen alteraciones epigenéticas por hipermetilación e inactivación epigenética del sitio promotor del gen hMLH1, en donde la mutación del gen BRAFv600 es un evento car...

  12. Chemoprevention of DMH-induced rat colon carcinoma initiation by combination administration of piroxicam and C-phycocyanin.

    Science.gov (United States)

    Saini, Manpreet Kaur; Vaiphei, Kim; Sanyal, Sankar Nath

    2012-02-01

    Cancer research illustrated that combinatorial studies can provide significant improvement in safety and effectiveness over the monotherapy regimens. A combination of two drugs may restrain precancerous colon polyps, opening a new possible opportunity for chemoprevention of colon cancer. In this context, chemopreventive efficacy of a combination regimen of C-phycocyanin, a biliprotein present in Spirulina platensis, a cyanobacterium, which is a selective cycloxygenase-2 (COX-2) inhibitor and piroxicam, a traditional non-steroidal anti-inflammatory drug was considered in 1,2 dimethylhyadrazine (DMH)-induced colon carcinogenesis in rats. Western blotting, immunohistochemistry, DNA fragmentation, fluorescent staining, PGE(2) enzyme immunoassay, and carrageenan-induced paw edema test were performed along with morphological and histological analysis. DMH treatment showed a rich presence of preneoplastic lesions such as multiple plaque lesions, aberrant crypt foci, and well-characterized dysplasia. These features were reduced with piroxicam and C-phycocyanin administration. The number of apoptotic cells was featured prominently in all the groups compared with DMH. DMH treatment revealed intact high molecular weight genomic DNA with no signs of laddering/DNA fragmentation while it was noticeable significantly in control and DMH + piroxicam + C-phycocyanin. DMH group showed highest COX-2 expression and PGE(2) level in comparison with other groups. Doses of piroxicam and C-phycocyanin used in the present study were established at an anti-inflammatory range. A combination regimen of piroxicam and C-phycocyanin, rather than individually has the much greater potential for reduction of DMH-induced colon cancer development and COX-2 being the prime possible target in such chemoprevention.

  13. Cyclic AMP-dependent secretion of Ca 19-9 by LS174T human colon carcinoma cells.

    Science.gov (United States)

    Macchia, Vincenzo; Gargiulo, Maria; Terracciano, Daniela; Di Carlo, Angelina; Mariano, Angela

    2002-01-01

    Prolonged increase of cyclic adenosine-monophosphate (cAMP) level in culture medium of a human colon cancer cell (LS174T) inhibits cellular growth and stimulates Ca 19-9 expression. The raise in cAMP level was produced by dibutyryl cyclic AMP (DBcAMP) or by forskolin an agent acting at the level of cAMP generation. Both these agents in a range of concentration between 10(-3)-10(-5) M have an inhibitory effect on the growth which is dose and time dependent. The inhibition was reversible as demonstrated by complete restoration of cell growth soon after the withdrawal of the substances from the culture medium. When cAMP levels in culture medium was raised, an increase in Ca 19-9 expression was observed and it appears that cyclic nucleotides have at least two effects: the first to cause rapid release of already synthesized Ca 19-9 and second to stimulate new antigen synthesis. The findings of the present study demonstrated that LS174T cells are unable to proliferate upon sustained accumulation of intracellular cyclic AMP suggesting the use of strategies able to increase cAMP levels for therapy of colon cancer. Furthermore, the finding that cAMP may also be a regulator of Ca 19-9 synthesis and release indicates the utility of cell line LS174T as a model for studies on the mechanism of synthesis and secretion of specific tumoral markers in colon cancer.

  14. Effects and Mechanism of Imatinib in Inhibiting Colon Cancer Cell Proliferation

    Science.gov (United States)

    Samei, Lv; Yaling, Pang; Lihua, Yang; Yan, Zhang; Shuyan, Jiang

    2016-01-01

    Background This study investigated the effects and mechanism of imatinib in inhibiting colon cancer cell proliferation. Material/Methods The SW480 cells were divided into 4 imatinib-treated groups: 0 μM, 1.25 μM, 2.5 μM, and 5μM. We analyzed the apoptosis and cell cycle of the 4 groups. The gene and protein expressions of p21, p27, HGF, and GAPDH were measured by RT-PCR and Western blot. Results Compared with the 0-μM imatinib-treated group, the apoptosis of 1.25-μM, 2.5-μM, and 5.0-μM treated groups was significantly induced (P<0.05, all). The G1 phase was significantly up-regulated in the 1.25-μM, 2.5-μM, and 5.0-μM treated groups compared with the 0-μM imatinib-treated group (P<0.05, respectively), but the S and G2 phase of 3 imatinib-treated groups were significantly down-regulated (P<0.05, all). The gene and protein expressions of p27 and HGF were significantly different among the 4 groups (P<0.05, all). Conclusions Imatinib inhibits proliferation of colon cancer cells by reducing HGF and increasing p27 in a dose-dependent manner. PMID:27799652

  15. Carcinomas neuroendocrinos de colon y recto: Experiencia de una unidad en seis años Neuroendocrine carcinomas of the colon and rectum: A unit's experience over six years

    Directory of Open Access Journals (Sweden)

    R. Vilallonga

    2008-01-01

    Full Text Available Introducción: los tumores neuroendocrinos de colon y recto son poco frecuentes. Suelen ser tumores poco diferenciados, diagnosticados por el patólogo y de especial agresividad en su comportamiento clínico. El pronóstico suele ser malo, con tendencia a la rápida metastatización. Material y métodos: se ha revisado la experiencia de una Unidad de Coloproctología durante un periodo de seis años. Se han revisado de manera retrospectiva los pacientes con un tumor de estirpe neuroendocrina. Se han excluido los tumores carcinoides. Resultados: durante este periodo, se han intervenido 2.155 pacientes por cáncer de colon y recto y se han hallado cinco pacientes con tumores neuroendocrinos. La edad media fue de 66 años, tres varones y dos hembras. Se localizaron uno en ciego, dos en recto y dos en sigma. Dos pacientes presentaban diseminación del tumor a distancia. Se realizó cirugía en todos los pacientes con quimioterapia posterior en dos de ellos. Un paciente falleció por insuficiencia hepática postoperatoria, otro a los dos meses y otro al año. Dos pacientes siguen vivos con un seguimiento medio de ocho meses. Conclusiones: los tumores neuroendocrinos son unos tumores de aparición rara en el colon y recto. La clínica de presentación no difiere de la que podrían tener los adenocarcinomas. En el momento del diagnóstico estos tumores suelen presentar enfermedad a distancia, como en dos de los cinco casos presentados, relacionándose con un mal pronóstico para el enfermo. El tratamiento quirúrgico y quimioterápico combinado es el que puede alargar más la supervivencia de los pacientes.Introduction: neuroendocrine tumours of the colon and rectum are infrequent. They are usually undifferentiated, easy to diagnose for the pathologist and are especially aggressive in their clinical behaviour. Prognosis is usually poor and they have a high tendency to metastase early. Material and methods: we have reviewed our experience in a

  16. miR-143 overexpression impairs growth of human colon carcinoma xenografts in mice with induction of apoptosis and inhibition of proliferation.

    Directory of Open Access Journals (Sweden)

    Pedro M Borralho

    Full Text Available BACKGROUND: MicroRNAs (miRNAs are aberrantly expressed in human cancer and involved in the (dysregulation of cell survival, proliferation, differentiation and death. Specifically, miRNA-143 (miR-143 is down-regulated in human colon cancer. In the present study, we evaluated the role of miR-143 overexpression on the growth of human colon carcinoma cells xenografted in nude mice (immunodeficient mouse strain: N: NIH(s II-nu/nu. METHODOLOGY/PRINCIPAL FINDINGS: HCT116 cells with stable miR-143 overexpression (Over-143 and control (Empty cells were subcutaneously injected into the flanks of nude mice, and tumor growth was evaluated over time. Tumors arose ∼ 14 days after tumor cell implantation, and the experiment was ended at 40 days after implantation. miR-143 was confirmed to be significantly overexpressed in Over-143 versus Empty xenografts, by TaqMan® Real-time PCR (p<0.05. Importantly, Over-143 xenografts displayed slower tumor growth compared to Empty xenografts from 23 until 40 days in vivo (p<0.05, with final volumes of 928±338 and 2512±387 mm(3, respectively. Evaluation of apoptotic proteins showed that Over-143 versus Empty xenografts displayed reduced Bcl-2 levels, and increased caspase-3 activation and PARP cleavage (p<0.05. In addition, the incidence of apoptotic tumor cells, assessed by TUNEL, was increased in Over-143 versus Empty xenografts (p<0.01. Finally, Over-143 versus Empty xenografts displayed significantly reduced NF-κB activation and ERK5 levels and activation (p<0.05, as well as reduced proliferative index, evaluated by Ki-67 immunohistochemistry (p<0.01. CONCLUSIONS: Our results suggest that reduced tumor volume in Over-143 versus Empty xenografts may result from increased apoptosis and decreased proliferation induced by miR-143. This reinforces the relevance of miR-143 in colon cancer, indicating an important role in the control of in vivo tumor progression, and suggesting that miR-143 may constitute a putative

  17. 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.

  18. Hyperplastic polyps of the colon and rectum - reclassification, BRAF and KRAS status in index polyps and subsequent colorectal carcinoma

    DEFF Research Database (Denmark)

    Janjua, Huma Gul Rehana; Høgdall, Estrid; Linnemann, Dorte

    2015-01-01

    (THP), sessile serrated lesions (SSL), and other lesions. All patients were confirmed in the Danish National Pathology Database for the occurrence of metachronous polyps/adenomas, colorectal cancer (CRC), and other gastrointestinal malignancies. Molecular pathology of the CRC were characterized...... in the follow-up period (1 patient had SSL, 4 had THP, and 2 had unspecified non-neoplastic lesions). Ten patients developed other gastrointestinal malignancies. The patient with SSL as index lesions who developed CRC harbored V600E BRAF mutation in both index lesion and the carcinoma. Sixteen percent...... of patients with SSL subsequently developed a neoplastic lesion. Further studies are needed to clarify the cancer risk of SSL....

  19. Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp transcription factors

    Directory of Open Access Journals (Sweden)

    Pathi Satya

    2011-08-01

    Full Text Available Abstract Background Betulinic acid (BA inhibits growth of several cancer cell lines and tumors and the effects of BA have been attributed to its mitochondriotoxicity and inhibition of multiple pro-oncogenic factors. Previous studies show that BA induces proteasome-dependent degradation of specificity protein (Sp transcription factors Sp1, Sp3 and Sp4 in prostate cancer cells and this study focused on the mechanism of action of BA in colon cancer cells. Methods The effects of BA on colon cancer cell proliferation and apoptosis and tumor growth in vivo were determined using standardized assays. The effects of BA on Sp proteins and Sp-regulated gene products were analyzed by western blots, and real time PCR was used to determine microRNA-27a (miR-27a and ZBTB10 mRNA expression. Results BA inhibited growth and induced apoptosis in RKO and SW480 colon cancer cells and inhibited tumor growth in athymic nude mice bearing RKO cells as xenograft. BA also decreased expression of Sp1, Sp3 and Sp4 transcription factors which are overexpressed in colon cancer cells and decreased levels of several Sp-regulated genes including survivin, vascular endothelial growth factor, p65 sub-unit of NFκB, epidermal growth factor receptor, cyclin D1, and pituitary tumor transforming gene-1. The mechanism of action of BA was dependent on cell context, since BA induced proteasome-dependent and proteasome-independent downregulation of Sp1, Sp3 and Sp4 in SW480 and RKO cells, respectively. In RKO cells, the mechanism of BA-induced repression of Sp1, Sp3 and Sp4 was due to induction of reactive oxygen species (ROS, ROS-mediated repression of microRNA-27a, and induction of the Sp repressor gene ZBTB10. Conclusions These results suggest that the anticancer activity of BA in colon cancer cells is due, in part, to downregulation of Sp1, Sp3 and Sp4 transcription factors; however, the mechanism of this response is cell context-dependent.

  20. Early Detection of Tumor Response by FLT/MicroPET Imaging in a C26 Murine Colon Carcinoma Solid Tumor Animal Model

    Directory of Open Access Journals (Sweden)

    Wan-Chi Lee

    2011-01-01

    Full Text Available Fluorine-18 fluorodeoxyglucose (18F-FDG positron emission tomography (PET imaging demonstrated the change of glucose consumption of tumor cells, but problems with specificity and difficulties in early detection of tumor response to chemotherapy have led to the development of new PET tracers. Fluorine-18-fluorothymidine (18F-FLT images cellular proliferation by entering the salvage pathway of DNA synthesis. In this study, we evaluate the early response of colon carcinoma to the chemotherapeutic drug, lipo-Dox, in C26 murine colorectal carcinoma-bearing mice by 18F-FDG and 18F-FLT. The male BALB/c mice were bilaterally inoculated with 1×105 and 1×106 C26 tumor cells per flank. Mice were intravenously treated with 10 mg/kg lipo-Dox at day 8 after 18F-FDG and 18F-FLT imaging. The biodistribution of 18F-FDG and 18F-FLT were followed by the microPET imaging at day 9. For the quantitative measurement of microPET imaging at day 9, 18F-FLT was superior to 18F-FDG for early detection of tumor response to Lipo-DOX at various tumor sizes (<0.05. The data of biodistribution showed similar results with those from the quantification of SUV (standard uptake value by microPET imaging. The study indicates that 18F-FLT/microPET is a useful imaging modality for early detection of chemotherapy in the colorectal mouse model.

  1. Glucocorticoid receptor alpha and beta variant expression is associated with ASF/SF2 splicing factor upregulation in HT-29 colon cancer and MCF-7 breast carcinoma cells.

    Science.gov (United States)

    Piotrowska, Hanna; Jagodzinski, Pawel P

    2009-04-01

    Transcriptional activity of NF-kappaB is inhibited by the liganded glucocorticoid receptor (GR), which exists mainly in two splice variants as functional GRalpha and nonfunctional GRbeta. We investigated the effect of 5-aza-2'-deoxycytidine (5-dAzaC), trichostatin A (TSA), and sodium butyrate (NaBu) on GRalpha,GRbeta and ASF/SF2 splicing factor expression in HT-29 colon and MCF-7 breast carcinoma cells. HT-29 and MCF-7 cells were cultured in the absence or in the presence of 5-dAzaC, TSA, and NaBu, followed by RNA and protein isolation. The transcript and protein levels of GRalpha, GRbeta ASF/SF2 were determined by reverse transcription, real-time quantitative PCR and Western blot analysis. We found that 5-dAzaC, TSA, and NaBu lead to an increase in GRalpha and ASF/SF2 transcript levels and a decrease in GRbeta transcript levels in HT-29 and MCF-7 cells. The 5-dAzaC, TSA, and NaBu resulted in increased GRalpha and ASF/SF2 protein levels and GRbeta protein downregulation in HT-29 cells. The most increased GRalpha protein expression in MCF-7 cells was observed with NaBu. However, all of these compounds inhibited GRbeta protein expression in MCF-7 cells. The MCF-7 cells treated with NaBu demonstrated a remarkable increase in ASF/SF2 protein expression. Because NF-kappaB is considered to be a factor in the augmentation of malignant properties of cells, treatment of tumors with 5-dAzaC, TSA, and NaBu may provide a novel approach to the enhancement of therapeutic effects of glucocorticoids in epithelial carcinomas.

  2. Management dilemma; a woman with cystic fibrosis and severe lung disease presenting with colonic carcinoma: a case report

    Directory of Open Access Journals (Sweden)

    Lees Andrea N

    2008-12-01

    Full Text Available Abstract Introduction There are increasing reports of bowel cancer in cystic fibrosis, suggesting a possible causal link. Individuals with cystic fibrosis who have advanced lung disease present a high operative risk, limiting curative treatment options in early bowel malignancy. Case presentation We describe a 41-year-old Caucasian woman with cystic fibrosis and severe lung disease who had been considered for lung transplantation, who presented with rectal bleeding and was found to have a Stage I adenocarcinoma of the sigmoid colon. After considerable discussion as to the operative risks, she underwent a laparoscopic resection and remains relatively well 1 year postoperatively with no recurrence. Conclusion We discuss the complexity of the management decisions for cystic fibrosis patients with severe lung disease and early stage colonic malignancy, particularly in the context of potential need for lung transplantation. The case demonstrates that cystic fibrosis patients with very severe lung function impairment may undergo laparoscopic abdominal surgical interventions without compromising postoperative airway clearance.

  3. Higher percentage of CD133+ cells is associated with poor prognosis in colon carcinoma patients with stage IIIB

    Directory of Open Access Journals (Sweden)

    Zhang Xin

    2009-07-01

    Full Text Available Abstract Background Cancer stem cell model suggested that tumor progression is driven by the overpopulation of cancer stem cells and eradicating or inhibiting the symmetric division of cancer stem cells would become the most important therapeutic strategy. However, clinical evidence for this hypothesis is still scarce. To evaluate the overpopulation hypothesis of cancer stem cells the association of percentage of CD133+ tumor cells with clinicopathological parameters in colon cancer was investigated since CD133 is a putative cancer stem cell marker shared by multiple solid tumors. Patients and methods Tumor tissues matched with adjacent normal tissues were collected from 104 stage IIIB colon cancer patients who were subject to radical resection between January, 1999 to July, 2003 in this center. The CD133 expression was examined with immunohistochemical staining. The correlation of the percentage of CD133+ cell with clinicopathological parameters and patients' 5-year survival was analyzed. Results The CD133+ cells were infrequent and heterogeneous distribution in the cancer tissue. Staining of CD133 was localized not only on the glandular-luminal surface of cancer cells but also on the invasive budding and the poorly differentiated tumors with ductal structures. Both univariate and multivariate survival analysis revealed that the percentage of CD133+ cancer cells and the invasive depth of tumor were independently prognostic. The patients with a lower percentage of CD133+ cancer cells (less than 5% were strongly associated with a higher 5-year survival rate than those with a higher percentage of CD133+ cancer cells (greater than or equal to 55%. Additionally, no correlation was obtained between the percentage of CD133+ cancer cells and the other clinicopathological parameters including gender, age, site of primary mass, pathologic types, grades, and invasive depth. Conclusion The fact that a higher percentage CD133+ cells were strongly associated

  4. Phase III trial assessing bevacizumab in stages II and III carcinoma of the colon: results of NSABP protocol C-08.

    Science.gov (United States)

    Allegra, Carmen J; Yothers, Greg; O'Connell, Michael J; Sharif, Saima; Petrelli, Nicholas J; Colangelo, Linda H; Atkins, James N; Seay, Thomas E; Fehrenbacher, Louis; Goldberg, Richard M; O'Reilly, Seamus; Chu, Luis; Azar, Catherine A; Lopa, Samia; Wolmark, Norman

    2011-01-01

    The National Surgical Adjuvant Breast and Bowel Project C-08 trial was designed to investigate the safety and efficacy of adding bevacizumab to modified FOLFOX6 (mFOLFOX6; ie, infusional/bolus fluorouracil, leucovorin, and oxaliplatin) for the adjuvant treatment of patients with stages II to III colon cancer. Patients received mFOLFOX6 every 2 weeks for 26 weeks alone or modified as FOLFOX6 + bevacizumab (5 mg/kg every 2 weeks for 52 weeks [ie, experimental group]). The primary end point was disease-free survival (DFS). Among 2,672 analyzed patients, demographic factors were well balanced by treatment. With a median follow-up of 35.6 months, the addition of bevacizumab to mFOLFOX6 did not result in an overall significant increase in DFS (hazard ratio [HR], 0.89; 95% CI, 0.76 to 1.04; P = .15). The point estimates for 3-year DFS for the overall population were 77.4% and 75.5% for the experimental and control arms, respectively. For patients with stages II and III diseases, these same estimates were 87.4% and 84.7%, respectively, for stage II and 74.2% and 72.4%, respectively, for stage III. Exploratory analyses found that the effect of bevacizumab on DFS was different before and after a 15-month landmark (time-by-treatment interaction P value < .0001). Bevacizumab had a strong effect before the landmark (HR, 0.61; 95% CI, 0.48 to 0.78; P < .001) but no significant effect after (HR, 1.22; 95% CI, 0.98 to 1.52; P = .076). Bevacizumab for 1 year with mFOLFOX6 does not significantly prolong DFS in stages II and III colon cancer. However, a significant but transient effect during bevacizumab exposure was observed in the experimental arm. We postulate that this observation reflects a biologic effect during bevacizumab exposure. Given the lack of improvement in DFS, the use of bevacizumab cannot be recommended for use in the adjuvant treatment of patients with colon cancer.

  5. A relationship between perioperative blood transfusion and recurrence of carcinoma of the sigmoid colon following potentially curative surgery.

    Science.gov (United States)

    Creasy, T S; Veitch, P S; Bell, P R

    1987-05-01

    Preoperative blood transfusions are used to improve graft survival in renal transplantation. If such an immunomodulating effect occurred in cancer surgery perioperative blood transfusion may be detrimental to patient outcome. A retrospective study of 68 patients undergoing potentially curative surgery for adenocarcinoma of the sigmoid colon, over a 10 year period was performed. Thirty-three patients (49%) had a perioperative blood transfusion of which two-thirds received either one or two units. Transfused patients had a poorer prognosis compared to non-transfused patients (0.28 and 0.53 five year product limit recurrence free fractions respectively; P less than 0.01 on generalised Savege test of entire recurrence free curves). Perioperative transfusion was the most sensitive prognostic indicator of recurrence on Cox proportional hazards regression analysis (relative risk 2.6; P less than 0.01, after adjustment for histological stage). Although a causal relationship is not proven, prospective work is urgently needed.

  6. Effects of Cultivated Wild Ginseng Herbal Acupuncture to the serum cytokine on Hepatic Metastatic Model using Colon26-L5 Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Byung Jun, Cho

    2006-02-01

    Full Text Available Objectives : This experiment was conducted to evaluate inhibitory effects against hepatic metastasis by cultivated wild ginseng Herbal Acupuncture. Methods : Colon26-L5 carcinoma cells were injected through hepatic portal vein to induce hepatic metastatic cancer. Afer treated cultivated wild ginseng Herbal Acupuncture and investigated various kinds of cytokine level using cytokine chip. Results : 1. Mice treated with cultivated wild ginseng Herbal Acupuncture reduced the level of IL-1α, IL-1β and TNF-α compared to the control group. 2. Mice treated with cultivated wild ginseng Herbal Acupuncture was not showed significant change in the level of IL-4, IL-10, IL-12 and INF-γ compared to the control group. 3. Observing the level of various kinds of cytokine, cultivated wild ginseng Herbal Acupuncture was suppressed pro-inflammatory cytokine. These findings indicate cultivated wild ginseng Herbal Acupuncture is possible to use the inflammatory disease and futher studies carry out for the explanation of anticancer mechanism.

  7. Insight into the effect of the vasopressin analog desmopressin on lung colonization by mammary carcinoma cells in BALB/c mice.

    Science.gov (United States)

    Garona, Juan; Pifano, Marina; Scursoni, Alejandra M; Gomez, Daniel E; Alonso, Daniel F; Ripoll, Giselle V

    2014-09-01

    Desmopressin (dDAVP) is a synthetic peptide analog of vasopressin with antidiuretic and hemostatic properties. Recent experimental evidence have suggested that dDAVP can inhibit metastasis formation by agonist action on V2 vasopressin receptors present in both tumor and endothelial cells. We have examined the kinetics of dDAVP effect during metastatic colonization and its potential association with hemostasis. The experimental metastasis assay was performed by injecting F3II mammary carcinoma cells into the lateral tail vein of syngeneic female BALB/c mice. Clinically relevant doses of dDAVP (0.3 to 2 μg/kg intravenously (i.v.)) produced a dose-dependent inhibition in the formation of lung nodules when administered during the first 24 hours after F3II tumor cell injection. The hemostatic agent tranexamic acid (10 mg/kg, i.v.) had no effect on metastasis formation in the same experimental conditions, while the anticoagulant enoxaparin (1 mg/kg, subcutaneously (s.c.)) did not modify the antimetastatic action of dDAVP. In vitro, dDAVP had a strong inhibitory effect on F3II cell colony formation. dDAVP interferes with early metastatic disease, and direct association of this effect with hemostatic mechanisms is unlikely. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  8. A novel Osmium-based compound targets the mitochondria and triggers ROS-dependent apoptosis in colon carcinoma.

    Science.gov (United States)

    Maillet, A; Yadav, S; Loo, Y L; Sachaphibulkij, K; Pervaiz, S

    2013-06-06

    Engagement of the mitochondrial-death amplification pathway is an essential component in chemotherapeutic execution of cancer cells. Therefore, identification of mitochondria-targeting agents has become an attractive avenue for novel drug discovery. Here, we report the anticancer activity of a novel Osmium-based organometallic compound (hereafter named Os) on different colorectal carcinoma cell lines. HCT116 cell line was highly sensitive to Os and displayed characteristic features of autophagy and apoptosis; however, inhibition of autophagy did not rescue cell death unlike the pan-caspase inhibitor z-VAD-fmk. Furthermore, Os significantly altered mitochondrial morphology, disrupted electron transport flux, decreased mitochondrial transmembrane potential and ATP levels, and triggered a significant increase in reactive oxygen species (ROS) production. Interestingly, the sensitivity of cell lines to Os was linked to its ability to induce mitochondrial ROS production (HCT116 and RKO) as HT29 and SW620 cell lines that failed to show an increase in ROS were resistant to the death-inducing activity of Os. Finally, intra-peritoneal injections of Os significantly inhibited tumor formation in a murine model of HCT116 carcinogenesis, and pretreatment with Os significantly enhanced tumor cell sensitivity to cisplatin and doxorubicin. These data highlight the mitochondria-targeting activity of this novel compound with potent anticancer effect in vitro and in vivo, which could have potential implications for strategic therapeutic drug design.

  9. A prospective cohort study to investigate cost-minimisation, of Traditional open, open fAst track recovery and laParoscopic fASt track multimodal management, for surgical patients with colon carcinomas (TAPAS study

    Directory of Open Access Journals (Sweden)

    van Duivendijk Peter

    2010-06-01

    Full Text Available Abstract Background The present developments in colon surgery are characterized by two innovations: the introduction of the laparoscopic operation technique and fast recovery programs such as the Enhanced Recovery After Surgery (ERAS recovery program. The Tapas-study was conceived to determine which of the three treatment programs: open conventional surgery, open 'ERAS' surgery or laparoscopic 'ERAS' surgery for patients with colon carcinomas is most cost minimizing? Method/design The Tapas-study is a three-arm multicenter prospective cohort study. All patients with colon carcinoma, eligible for surgical treatment within the study period in four general teaching hospitals and one university hospital will be included. This design produces three cohorts: Conventional open surgery is the control exposure (cohort 1. Open surgery with ERAS recovery (cohort 2 and laparoscopic surgery with ERAS recovery (cohort 3 are the alternative exposures. Three separate time periods are used in order to prevent attrition bias. Primary outcome parameters are the two main cost factors: direct medical costs (real cost price calculation and the indirect non medical costs (friction method. Secondary outcome parameters are mortality, complications, surgical-oncological resection margins, hospital stay, readmission rates, time back to work/recovery, health status and quality of life. Based on an estimated difference in direct medical costs (highest cost factor of 38% between open and laparoscopic surgery (alfa = 0.01, beta = 0.05, a group size of 3×40 = 120 patients is calculated. Discussion The Tapas-study is three-arm multicenter cohort study that will provide a cost evaluation of three treatment programs for patients with colon carcinoma, which may serve as a guideline for choice of treatment and investment strategies in hospitals. Trial registration ISRCTN44649165.

  10. Characterization of the long-term pharmacokinetics of bevacizumab following last dose in patients with resected stage II and III carcinoma of the colon.

    Science.gov (United States)

    Li, Jing; Gupta, Manish; Jin, Denise; Xin, Yan; Visich, Jennifer; Allison, David E

    2013-03-01

    The study characterizes the long-term pharmacokinetics (PK) following last dose of bevacizumab as adjuvant therapy in patients with resected stage II and III colon carcinoma in a Phase III clinical study (AVF3077s). Patients in AVF3077s received bevacizumab (5 mg/kg every 2 weeks) as adjuvant therapy for 1 year. Following the last dose bevacizumab concentration, data at 3 and 6 months were used to characterize long-term bevacizumab PK based on the population-modeling approach. The long-term bevacizumab PK were consistent with previously reported results based on short-term bevacizumab PK. The clearance (CL), central volume of distribution (V(1)), intercompartmental clearance (Q), and the peripheral volume of distribution (V(2)) were 214 mL/day, 2,830 mL, 636 mL/day, and 2,490 mL, which correspond to a disposition and elimination half-life of 1.33 and 19.1 days, respectively. The empirical Bayes estimates of median post-treatment bevacizumab drug levels at 3 and 6 months were 6.14 and 0.23 μg/mL, respectively. For test covariates, the change in CL and V(1) of bevacizumab was less than 20% of the typical value. Body weight is the important covariate explaining the inter-individual variability on CL and V(1). Long-term bevacizumab PK in this study was predictable based on short-term PK data from metastatic settings in other tumor types. An exploratory analysis demonstrated no apparent association of the tested covariates with bevacizumab PK. Further, the extended serum persistence of bevacizumab following last dose should be considered in clinical study designs and post-treatment evaluations that may be affected by bevacizumab.

  11. Evaluation of antioxidant activity and antiproliferative effect of fruit juices enriched with Pycnogenol® in colon carcinoma cells. The effect of in vitro gastrointestinal digestion.

    Science.gov (United States)

    Frontela-Saseta, Carmen; López-Nicolás, Rubén; González-Bermúdez, Carlos A; Peso-Echarri, Patricia; Ros-Berruezo, Gaspar; Martínez-Graciá, Carmen; Canali, Raffaella; Virgili, Fabio

    2011-12-01

    The aim of this study was to examine the effect of in vitro gastrointestinal digestion on the antioxidant and antiproliferative effect of fruit juices enriched with Pycnogenol® (0.5 g/L) on a colon carcinoma cell line (Caco-2). The total phenolic concentration (TPC), antioxidant activity and inhibition cell growth were studied in fresh and digested pineapple juice and red fruits juice (both enriched with pine bark extract and not). After in vitro digestion the level of detectable phenolic compounds (expressed as gallic acid equivalent) was higher in both pineapple and red fruits juices enriched with Pycnogenol® than in non-enriched commercial juices (155.6 mg/100 mL vs 94.6 mg/100 mL and 478.5 mg/100 mL vs 406.9 mg/100 mL, respectively). Increased antioxidant activity (measured by 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and oxygen radical absorbance capacity assay (ORAC) methods) was observed in digested enriched juices with respect to the same samples before digestion. Pycnogenol® enrichment led to a high antiproliferative effect between 24 and 72 h of incubation with undigested pineapple juice compared with the non-enriched juice. It can be concluded that enrichment of fruit juices with Pycnogenol® provides a source of phenolic compounds with high stability to in vitro gastrointestinal conditions; however, the antioxidant properties of fruit juices were affected to a different extent. Copyright © 2011 John Wiley & Sons, Ltd.

  12. Germline mutations in PMS2 and MLH1 in individuals with solitary loss of PMS2 expression in colorectal carcinomas from the Colon Cancer Family Registry Cohort.

    Science.gov (United States)

    Rosty, Christophe; Clendenning, Mark; Walsh, Michael D; Eriksen, Stine V; Southey, Melissa C; Winship, Ingrid M; Macrae, Finlay A; Boussioutas, Alex; Poplawski, Nicola K; Parry, Susan; Arnold, Julie; Young, Joanne P; Casey, Graham; Haile, Robert W; Gallinger, Steven; Le Marchand, Loïc; Newcomb, Polly A; Potter, John D; DeRycke, Melissa; Lindor, Noralane M; Thibodeau, Stephen N; Baron, John A; Win, Aung Ko; Hopper, John L; Jenkins, Mark A; Buchanan, Daniel D

    2016-02-19

    Immunohistochemistry for DNA mismatch repair proteins is used to screen for Lynch syndrome in individuals with colorectal carcinoma (CRC). Although solitary loss of PMS2 expression is indicative of carrying a germline mutation in PMS2, previous studies reported MLH1 mutation in some cases. We determined the prevalence of MLH1 germline mutations in a large cohort of individuals with a CRC demonstrating solitary loss of PMS2 expression. This cohort study included 88 individuals affected with a PMS2-deficient CRC from the Colon Cancer Family Registry Cohort. Germline PMS2 mutation analysis (long-range PCR and multiplex ligation-dependent probe amplification) was followed by MLH1 mutation testing (Sanger sequencing and multiplex ligation-dependent probe amplification). Of the 66 individuals with complete mutation screening, we identified a pathogenic PMS2 mutation in 49 (74%), a pathogenic MLH1 mutation in 8 (12%) and a MLH1 variant of uncertain clinical significance predicted to be damaging by in silico analysis in 3 (4%); 6 (9%) carried variants likely to have no clinical significance. Missense point mutations accounted for most alterations (83%; 9/11) in MLH1. The MLH1 c.113A> G p.Asn38Ser mutation was found in 2 related individuals. One individual who carried the MLH1 intronic mutation c.677+3A>G p.Gln197Argfs*8 leading to the skipping of exon 8, developed 2 tumours, both of which retained MLH1 expression. A substantial proportion of CRCs with solitary loss of PMS2 expression are associated with a deleterious MLH1 germline mutation supporting the screening for MLH1 in individuals with tumours of this immunophenotype, when no PMS2 mutation has been identified. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  13. Cytotoxic effects of palladium (II) and platinum (II) complexes with O,O'-dialkyl esters of (S,S)-ethylenediamine-N,N'-di-2-(4-methyl) pentanoic acid on human colon cancer cell lines.

    Science.gov (United States)

    Volarevic, V; Vujic, J M; Milovanovic, M; Kanjevac, T; Volarevic, A; Trifunovic, S R; Arsenijevic, N

    2013-01-01

    As novel therapeutic agents relevant to colon cancer therapy are explored continuously, we tested 4 R2edda-type ligand precursors O,O'-dialkyl esters of (S,S)-ethylenediamine-N,N'-di-2-(4-methyl)pentanoic acid (L1.2HCl-L4.2HCl) and corresponding palladium(II) and platinum(II) complexes against the human colon cancer cell lines CaCo-2, SW480 and HCT116. The effects of the tested compounds on cell viability were determined using MTT colorimetric technique. Analysis of cancer cell viability showed that all tested ligand precursors, palladium(II) and platinum(II) complexes were cytotoxic on human colon cancer cells in dose-dependent manner. The cytotoxic activity of all palladium(II) and platinum(II) complexes toward selected cancer cells was significantly higher in comparison to cisplatin. Among the tested platinum(II) and palladium(II) complexes the lowest activity was observed for the compounds with the shortest ester chain and the highest activity was noted for palladium(II) complex No.2 with the n-Pr group in ester chain and for platinum(II) complex No.7 with the n-Bu group in ester chain. Palladium(II) complex No.2 and platinum(II) complex No.7 seem to be good candidates for future pharmacological evaluation in the field of colon cancer research and treatment.

  14. Calreticulin is a fine tuning molecule in epibrassinolide-induced apoptosis through activating endoplasmic reticulum stress in colon cancer cells.

    Science.gov (United States)

    Obakan-Yerlikaya, Pinar; Arisan, Elif Damla; Coker-Gurkan, Ajda; Adacan, Kaan; Ozbey, Utku; Somuncu, Berna; Baran, Didem; Palavan-Unsal, Narcin

    2017-06-01

    Epibrassinolide (EBR), a member of brassinostreoids plant hormones with cell proliferation promoting role in plants, is a natural polyhydroxysteroid with structural similarity to steroid hormones of vertebrates. EBR has antiproliferative and apoptosis-inducing effect in various cancer cells. Although EBR has been shown to affect survival and mitochondria-mediated apoptosis pathways in a p53-independent manner, the exact molecular targets of EBR are still under investigation. Our recent SILAC (Stable Isotope Labeling by Amino Acids in Cell Culture) data showed that the most significantly altered protein after EBR treatment was calreticulin (CALR). CALR, a chaperone localized in endoplasmic reticulum (ER) lumen, plays role in protein folding and buffering Ca2+ ions. The alteration of CALR may cause ER stress and unfolded protein response correspondingly the induction of apoptosis. Unfolded proteins are conducted to 26S proteasomal degradation following ubiquitination. Our study revealed that EBR treatment caused ER stress and UPR by altering CALR expression causing caspase-dependent apoptosis in HCT 116, HT29, DLD-1, and SW480 colon cancer cells. Furthermore, 48 h EBR treatment did not caused UPR in Fetal Human Colon cells (FHC) and Mouse Embryonic Fibroblast cells (MEF). In addition our findings showed that HCT 116 colon cancer cells lacking Bax and Puma expression still undergo UPR and related apoptosis. CALR silencing and rapamycin co-treatment prevented EBR-induced UPR and apoptosis, whereas 26S proteasome inhibition further increased the effect of EBR in colon cancer cells. All these findings showed that EBR is an ER stress and apoptotic inducer in colon cancer cells without affecting non-malignant cells. © 2017 Wiley Periodicals, Inc.

  15. Novel snail1 target proteins in human colon cancer identified by proteomic analysis.

    Directory of Open Access Journals (Sweden)

    María Jesús Larriba

    2010-04-01

    Full Text Available The transcription factor Snail1 induces epithelial-to-mesenchymal transition (EMT, a process responsible for the acquisition of invasiveness during tumorigenesis. Several transcriptomic studies have reported Snail1-regulated genes in different cell types, many of them involved in cell adhesion. However, only a few studies have used proteomics as a tool for the characterization of proteins mediating EMT.We identified by proteomic analysis using 2D-DIGE electrophoresis combined with MALDI-TOF-TOF and ESI-linear ion trap mass spectrometry a number of proteins with variable functions whose expression is modulated by Snail1 in SW480-ADH human colon cancer cells. Validation was performed by Western blot and immunofluorescence analyses. Snail1 repressed several members of the 14-3-3 family of phosphoserine/phosphothreonine binding proteins and also the expression of the Proliferation-associated protein 2G4 (PA2G4 that was mainly localized at the nuclear Cajal bodies. In contrast, the expression of two proteins involved in RNA processing, the Cleavage and polyadenylation specificity factor subunit 6 (CPSF6 and the Splicing factor proline/glutamine-rich (SFPQ, was higher in Snail1-expressing cells than in controls. The regulation of 14-3-3epsilon, 14-3-3tau, 14-3-3zeta and PA2G4 by Snail1 was reproduced in HT29 colon cancer cells. In addition, we found an inverse correlation between 14-3-3sigma and Snail1 expression in human colorectal tumors.We have identified a set of novel Snail1 target proteins in colon cancer that expand the cellular processes affected by Snail1 and thus its relevance for cell function and phenotype.

  16. Therapeutic efficacy and microSPECT/CT imaging of {sup 188}Re-DXR-liposome in a C26 murine colon carcinoma solid tumor model

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Y.-J.; Chang, C.-H.; Yu, C.-Y.; Chang, T.-J.; Chen, L.-C. [Institute of Nuclear Energy Research, Taoyuan, Taiwan (China); Chen, M.-H. [National Health Research Institutes, Miaoli, Taiwan (China); Lee, T.-W. [Institute of Nuclear Energy Research, Taoyuan, Taiwan (China); Ting Gann [National Health Research Institutes, Miaoli, Taiwan (China)], E-mail: gann.ting@msa.hinet.net

    2010-01-15

    Nanocarriers can selectively target cancer sites and carry payloads, thereby improving diagnostic and therapeutic effectiveness and reducing toxicity. The objective of this study was to investigate the therapeutic efficacy of a new co-delivery radiochemotherapeutics of {sup 188}Re-N,N-bis (2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA)-labeled pegylated liposomal doxorubicin (DXR) ({sup 188}Re-DXR-liposome) in a C26 murine colon carcinoma solid tumor model. To evaluate the targeting and localization of {sup 188}Re-DXR-liposome in C26 murine tumor-bearing mice, biodistribution, microSPECT/CT imaging and pharmacokinetic studies were performed. The antitumor effect of {sup 188}Re-DXR-liposome was assessed by tumor growth inhibition, survival ratio and histopathological hematoxylin-eosin staining. The tumor target and localization of the nanoliposome delivery radiochemotherapeutics of {sup 188}Re-DXR-liposome were demonstrated in the biodistribution, pharmacokinetics and in vivo nuclear imaging studies. In the study on therapeutic efficacy, the tumor-bearing mice treated with bimodality radiochemotherapeutics of {sup 188}Re-DXR-liposome showed better mean tumor growth inhibition rate (MGI) and longer median survival time (MGI=0.048; 74 days) than those treated with radiotherapeutics of {sup 188}Re-liposome (MGI=0.134; 60 days) and chemotherapeutics of Lipo-Dox (MGI=0.413; 38 days). The synergistic tumor regression effect was observed with the combination index (CI) exceeding 1 (CI=1.145) for co-delivery radiochemotherapeutics of {sup 188}Re-DXR-liposome. Two (25%) of the mice treated with radiochemotherapeutics were completely cured after 120 days. The therapeutic efficacy of radiotherapeutics of {sup 188}Re-liposome and the synergistic effect of the combination radiochemotherapeutics of {sup 188}Re-DXR-liposome have been demonstrated in a C26 murine solid tumor animal model, which pointed to the potential benefit and promise of the co-delivery of

  17. GIVIO-SITAC 01: A randomized trial of adjuvant 5-fluorouracil and folinic acid administered to patients with colon carcinoma--long term results and evaluation of the indicators of health-related quality of life. Gruppo Italiano Valutazione Interventi in Oncologia. Studio Italiano Terapia Adiuvante Colon.

    Science.gov (United States)

    Zaniboni, A; Labianca, R; Marsoni, S; Torri, V; Mosconi, P; Grilli, R; Apolone, G; Cifani, S; Tinazzi, A

    1998-06-01

    In 1989, the authors began a randomized trial to determine whether 5-fluorouracil and high dose folinic acid (HD-FUFA) would increase the event free and overall survival of patients with resectable Dukes B and C (AJCC/UICC Stage II and Stage III) colon carcinoma, and to assess the toxicity of the treatment and its impact on selected health-related quality-of-life indicators. Early results were published as a part of an international multicenter pooled analysis (IMPACT) in 1995. The purpose of this report is to update the survival data for patients enrolled in the trial and describe their reported perceptions of their own health and quality of life. The trial involved multiple treatment centers, with a centralized randomization between surgery alone and surgery with chemotherapy. The HD-FUFA regimen employed consisted of 5-fluorouracil (370 mg/m2) plus folinic acid (200 mg/m2) administered daily for 5 days every 4 weeks for 6 cycles. Patients' perceptions of their own health status were obtained by means of 3 self-administered questionnaires, which were completed by patients at the time of discharge from the treatment center and at 6 and 24 months after randomization. Overall, 888 patients with resected Dukes B2 and C colon carcinoma were enrolled in the trial. HD-FUFA significantly reduced mortality by 25% (95% confidence interval, 5-41%; P=0.02) and events by 31% (95% confidence interval, 14-45%; P < or = 0.001). Compliance with treatment was good; more than 80% of patients completed the planned therapy. Toxicity was mild, and oral mucositis was the main side effect. None of the health-related quality-of-life parameters investigated (emotional status, worry about the future, changes in social life, impact of the disease, follow-up, and global quality of life) seemed to be affected by the treatment to which patients were allocated. A positive trend in the evolution of patients' psychologic status was observed. Long term results of this SITAC study confirm that HD

  18. The Effect of Sulfated (1→3-α-l-Fucan from the Brown Alga Saccharina cichorioides Miyabe on Resveratrol-Induced Apoptosis in Colon Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Olesia S. Vishchuk

    2013-01-01

    Full Text Available Accumulating data clearly indicate that the induction of apoptosis by nontoxic natural compounds is a potent defense against the development and progression of many malignancies, including colon cancer. Resveratrol and the fucoidans have been shown to possess potent anti-tumor activity in vitro and in vivo. The aim of the present study was to examine whether the combination of a fucoidan from the brown alga Saccharina cichorioides Miyabe and resveratrol would be an effective preventive and/or therapeutic strategy against colon cancer. Based on NMR spectroscopy and MALDI-TOF analysis, the fucoidan isolated and purified from Saccharina cichorioides Miyabe was (1→3-α-l-fucan with sulfate groups at C2 and C4 of the α-l-fucopyranose residues. The fucoidan enhanced the antiproliferative activity of resveratrol at nontoxic doses and facilitated resveratrol-induced apoptosis in the HCT 116 human colon cancer cell line. Apoptosis was realized by the activation of initiator caspase-9 and effector caspase-7 and -3, followed by the cleavage of PARP. Furthermore, significant inhibition of HCT 116 colony formation was associated with the sensitization of cells to resveratrol by the fucoidan. Taken together, these results demonstrate that the combination of the algal fucoidan with resveratrol may provide a potential therapy against human colon cancer.

  19. Regulation of stem cell self-renewal and differentiation by Wnt and Notch are conserved throughout the adenoma-carcinoma sequence in the colon

    NARCIS (Netherlands)

    Prasetyanti, Pramudita Ramadhina; Zimberlin, Cheryl Doreen; Bots, Michael; Vermeulen, Louis; Melo, Felipe De Sousa E.; Medema, Jan Paul

    2013-01-01

    Colon cancer stem cells are shown to be the self-renewing cells within a tumor that give rise to all lineages of more differentiated tumor cells. In this respect they are remarkably similar to their non-malignant counterparts that orchestrate the intestinal lining. This suggests that, despite the

  20. In vivo targeting of surface-modified liposomes to metastatically growing colon carcinoma cells and sinusoidal endothelial cells in the rat liver.

    NARCIS (Netherlands)

    Scherphof, GL; Kamps, JAAM; Koning, GA

    1997-01-01

    We prepared immunoliposomes by covalent coupling of a randomly thiolated monoclonal antibody against the rat colon adenocarcinoma cell line CC531 to MPB-PE on the outer surface of conventional as well as PEGylated liposomes of about 100-nm diameter. We attempted to target these immunoliposomes in

  1. Right sided colon cancer at Olabisi Onabanjo University Teaching ...

    African Journals Online (AJOL)

    Recent studies suggest that right sided colon cancer may have a different clinicopathological behaviour and prognosis from carcinoma in the rest of the colon and especially the rectum. Reports in the Nigerian literature had usually considered colon and rectal cancer together, thereby masking these differences. This study is ...

  2. HNPCC-associated synchronous early-stage signet-ring cell carcinomas of colonic origin. A comparative morphological and immunohistochemical study of an intramucosal and a submucosal example

    DEFF Research Database (Denmark)

    Klarskov, Louise; Bernstein, Inge; Holck, Susanne

    2008-01-01

    synchronous early-stage SRCC, developed in a 65-year-old hereditary nonpolyposis colorectal cancer male patient with a known disease-causing mutation in MLH1. A right hemicolectomy specimen comprised a 15-mm intramucosal cecal lesion, featuring zones of conventional tubular adenoma and intraepithelial SRCC...... as well as tumor cells multifocally permeating the lamina propria and a 12-mm submucosally expanding SRCC of the ascending colon. The intramucosal and intraepithelial as well as stromal lesional cells displayed a normal membranous expression of beta-catenin and E-cadherin; submucosally infiltrating cells...

  3. Tratamiento local de metástasis cutánea facial de cáncer de colon mediante colgajo submentoniano Local management of colon carcinoma metasasis in the face with a submental flap

    Directory of Open Access Journals (Sweden)

    A. Acosta Arencibia

    2010-12-01

    Full Text Available Las metástasis cutáneas de los tumores del aparato digestivo son lesiones infrecuentes que aparecen en pacientes con estadíos avanzados de la enfermedad, frecuentemente ya intervenidos del tumor primario. Son lesiones que aparecen de novo, de características variables y crecimiento rápido; suelen localizarse en tronco o extremidades inferiores y se diagnostican precozmente, lo que hace fácil su extirpación y el cierre directo del defecto. Presentamos el caso de un paciente con cáncer de colon en estadío avanzado con lesión metastásica facial de 6 cm de diámetro en mejilla derecha. Esta lesión ulcerada y maloliente, precisaba curas diarias y empeoraba la calidad de vida del paciente. Se procedió a su extirpación y para cobertura realizamos un colgajo submentoniano ipsilateral con excelente resultado. Este colgajo proporciona un tejido muy parecido al del defecto, creando mínimas secuelas de la zona donante que queda oculta en el área de sombra submandibular, por lo que representa una alternativa terapéutica ideal en defectos faciales de tamaño medio.Cutaneous metastasis of the digestive tract are infrequent lesions appearing in patients with advanced disease. Most of these patients have been already operated of their primary tumour. Lesions are variable in aspect, arising de novo and evolving with rapid growth. They usually lie in the trunk or lower extremities thus facilitating an early diagnosis and management with simple extirpation and direct closure. A case-report of a patient with advanced colonic cancer is here presented. At admission he presented a cutaneous matastasic lesion in the right cheek; it was a 6 cm ulcerated, bad -smelling lesion which needed daily dressings affecting patient's normal life. The lesion was removed using successfully a submental flap as coverage. The submental flap provides a very similar tissue to facial defects, leaving no donor area sequelae which is in addition well hidden, being

  4. Mucinous Adenocarcinoma of Colon

    OpenAIRE

    Jamshed Akhtar; Soofia Ahmed; Naima Zamir

    2010-01-01

    Bleeding per rectum is a common complaint in pediatric age group and mostly relates to benign conditions. Underlying colorectal carcinoma is a rare cause and carries a poor prognosis. We report two cases of mucinous adenocarcinoma of colon, one in a 9 years old male and other in a female of 12 years. The boy presented with rectal bleeding and increasing constipation of more than three years duration. He had mucinous adenocarcinoma (T3N0MX) of rectosigmoid region and underwent local complete r...

  5. Colonic angiodysplasia

    Energy Technology Data Exchange (ETDEWEB)

    Vallee, C.; Legmann, P.; Garnier, T.; Levesque, M.; Favriel, J.M.

    1984-11-01

    The main clinical, endoscopic and radiographic findings in thirty documented cases of colonic angiodysplasia or vacular ectasia are described. We emphasise the association with colonic diverticulosis and cardiovascular pathology, describe the histological changes, summarize the present physiopathological hypothesis, and consider the various therapeutic approaches.

  6. Neurofibromatosis tipo 1 asociado a tumor maligno de la vaina de nervio periférico y a carcinoma de colon

    Directory of Open Access Journals (Sweden)

    Rubén Valle

    2009-09-01

    Full Text Available La neurofibromatosis tipo 1 es una enfermedad autosómica dominante, producida por la mutación del gen de la neurofibrina, localizado en el cromosoma 17q11.2. Esta enfermedad presenta una diversidad de manifestaciones clínicas y predisposición al desarrollo de tumores, lo cual explica la elevada mortalidad. Presentamos el caso de una paciente con diagnóstico de neurofibromatosis tipo 1, quién desarrolló un tumor maligno de la vaina del nervio periférico y cáncer de colon. Se revisa la literatura y los factores clínicos, de imagen e histológicos que se asocian a la transformación maligna de los neurofibromas.

  7. Triple therapy with octreotide, galanin, and serotonin reduces the size and blood vessel density and increases apoptosis of a rat colon carcinoma.

    Science.gov (United States)

    El-Salhy, Magdy; Sitohy, Basel; Norrgård, Orjan

    2003-03-28

    A rat colonic adenocarcinoma was implanted subcutaneously in female nude (C57BL/6JBom-nu) mice. After 7 days, the animals were divided into different groups. One group received triple therapy with octreotide, galanin, and serotonin, 10 microg/kg body weight of each, twice daily. The second group served as controls and received only saline solution. Three groups received 10 microg/kg body weight twice daily of octreotide, galanin, or serotonin. The last group consisted of controls that received only saline solution. The treatment lasted for 5 days. The tumour volume, wet weight, and relative volume density of blood vessels were significantly decreased after the triple treatment, as compared to controls. Apoptotic index was significantly increased, but the proliferation index was not affected in the group of mice that received triple therapy. There was no significant difference between controls and mice treated with octreotide, galanin, or serotonin regarding tumour volume or weight. The relative volume density of blood vessels was decreased in tumours treated with galanin, but not with octreotide or serotonin. There was no statistical difference in the proliferation index between controls and animals treated with octreotide, galanin, or serotonin, as compared with controls. Tumour necrosis and increased apoptosis may be responsible for the reduction in the volume and weight of the tumour after triple therapy. Tumour necrosis may be caused by the induction of tumour ischemia due to a reduction in tumour blood flow, which is caused by decreased incidence of tumour-feeding blood vessels, and by constriction of tumour-feeding arterioles. These results are promising and may offer treatment for colon cancer. Copyright 2002 Elsevier Science B.V.

  8. Efficacy of recombinant adeno-associated viral vectors serotypes 1, 2, and 5 for the transduction of pancreatic and colon carcinoma cells.

    Science.gov (United States)

    Teschendorf, Christian; Emons, Barbara; Muzyczka, Nicholas; Graeven, Ullrich; Schmiegel, Wolff

    2010-06-01

    The development of efficient and specific vector systems remains a central issue in gene therapy. Several different adeno-associated virus (AAV) serotypes have so far been characterized so far which show different tissue tropisms. The vectors used here contained AAV2 transgene cassette containing green fluorescent protein (GFP) in AAV1, AAV2, or AAV5 capsids, producing the recombinant pseudotypes rAAV2/1, rAAV2/2, and rAAV2/5. The transduction efficiency of the different pseudotyped AAV vectors was tested in vitro in pancreatic and colon cancer cells lines (HT-29, BXPC3, and Hs766T). For all three serotypes, the percentage of GFP-positive cells was below 10% at multiplicities of infection (MOI) 100 rAAV vectors when used alone for infection. However, transduction efficiency for rAAV vectors increased dramatically when the cells were co-infected with wild-type adenovirus (wtAd). The percentage of GFP-positive cells ranged from 19.8-65.3% for AAV2/1 and 16.9-70.2% for AAV2/5, respectively. It was highest for rAAV2/2, at 40.9-88.4%. Variation between the cell lines was observed, with BXPC3 scoring the highest transduction rates and HT-29 the lowest. This study indicates that vectors based on distinct AAV serotypes 1, 2, and 5 all transduce pancreatic and colon cell lines poorly when used alone. Co-infection with wtAd increase transduction rates dramatically indicating that slow second-strand synthesis is a reason for the poor transduction efficiency. Due to the poor transduction rates, none of the rAAV serotypes tested here seem to be feasible for the treatment of malignant tumors.

  9. Neurotensin Phosphorylates GSK-3α/β through the Activation of PKC in Human Colon Cancer Cells

    Directory of Open Access Journals (Sweden)

    Qingding Wang

    2006-09-01

    Full Text Available Neurotensin (NT, a gastrointestinal hormone, binds its receptor [neurotensin receptor (NTR] to regulate the growth of normal and neoplastic intestinal cells; molecular mechanisms remain largely undefined. Glycogen synthase kinase-3 (GSK-3 regulates diverse cellular processes, including cell growth and apoptosis. Here, we show that NT induces the phosphorylation of GSK-3α/β in the human colon cancer cell line HT29, HCT116, or SW480, which possesses high-affinity NTR. The effect of NT was blocked by inhibitors of protein kinase C (PKC, but not by inhibitors of mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK1 or phosphatidylinositol-3 kinase, suggesting a predominant role for PKC in GSK-3β phosphorylation by NT. Pretreatment with Gö6976 (which inhibits PKCα and PKCβ1 or downregulation of endogenous PKCα or PKCβ1 blocked NT-mediated GSK-3β (but not GSK-3α phosphorylation. Moreover, a selective PKCβ inhibitor, LY379196, reduced NT-mediated GSK-3β (but not GSK-3α phosphorylation, suggesting a role for PKCbβ in the NT-mediated phosphorylation of GSK-3β and an undefined kinase in the NT-mediated phosphorylation of GSK-3α. Treatment with NT or the GSK-3 inhibitor SB216763 increased the expression of cyclin D1, a downstream effector protein of GSK-3 and a critical protein for the proliferation of various cells. Our results indicate that NT uses PKC-dependent pathways to modulate GSK-3, which may play a role in the NT regulation of intestinal cell growth.

  10. Excluding Lynch syndrome in a female patient with metachronous DNA mismatch repair deficient colon- and ovarian cancer

    NARCIS (Netherlands)

    S. Crobach (Stijn); Jansen, A.M.L. (Anne M. L.); Ligtenberg, M.J.L. (Marjolein J. L.); Koopmans, M. (Marije); M. Nielsen (Maartje); F.J. Hes (Frederik); J.T. Wijnen (Juul); W.N.M. Dinjens (Winand); T. van Wezel (Tom); H. Morreau (Hans)

    2017-01-01

    textabstractPatients synchronously or metachronously presenting with ovarian and colon cancer can pose diagnostic challenges. A primary colon carcinoma can metastasize to one or both ovaries, two independent primary tumors can arise or an ovarian carcinoma can metastasize to the colon. Clinical and

  11. Metástase cutânea rara de provável carcinoma basaloide de cólon simulando granuloma piogênico Rare cutaneous metastasis from a probable basaloid carcinoma of the colon mimicking pyogenic granuloma

    Directory of Open Access Journals (Sweden)

    Gustavo Costa Verardino

    2011-06-01

    Full Text Available As acrometástases, principalmente para as mãos, são incomuns e representam cerca de 0,0070,2% de todas as lesões metastáticas. O pulmão é o sítio de origem mais comum, colaborando com 4050% dos casos relatados na literatura. Os rins e mamas são outras localizações também relacionadas a neoplasias que metastatizam para as mãos, além de, mais raramente, trato gastrointestinal, outros tumores sistêmicos e sarcomas. Seu diagnóstico precoce é difícil, pois pode ser assintomático, se assemelhar a tenossinovite, artrite, paroníquia, granuloma piogênico ou infecção local. No presente relato, os autores apresentam paciente com diagnóstico de acrometástase, em ambos os quartos quirodáctilos, oriunda de carcinoma basaloide de canal anal, com pobre resposta à radioterapiaAcrometastasis is a rare occurrence, especially when affecting the hands. It represents around 0.007-0.2% of all metastatic lesions. The most common site of origin is the lung, accounting for 40-50% of all cases reported in the literature. Kidneys and breasts are other sites also associated with neoplastic lesions that disseminate to the hands. More rarely, the site of origin may be the gastrointestinal tract or other systemic tumors or sarcomas. Early diagnosis is difficult, since the condition may be asymptomatic or may mimic tenosynovitis, arthritis, paronychia, pyogenic granuloma or a local infection. In the present paper, the authors report on a patient with the diagnosis of acrometastasis on both hands originating from a basaloid carcinoma of the anal canal. Response to radiotherapy was poor

  12. Intra-tumoral heterogeneity in metastatic potential and survival signaling between iso-clonal HCT116 and HCT116b human colon carcinoma cell lines.

    Directory of Open Access Journals (Sweden)

    Sanjib Chowdhury

    Full Text Available Colorectal cancer (CRC metastasis is a leading cause of cancer-related deaths in the United States. The molecular mechanisms underlying this complex, multi-step pathway are yet to be completely elucidated. Recent reports have stressed the importance of intra-tumoral heterogeneity in the development of a metastatic phenotype. The purpose of this study was to characterize the intra-tumoral phenotypic heterogeneity between two iso-clonal human colon cancer sublines HCT116 and HCT116b on their ability to undergo metastatic colonization and survive under growth factor deprivation stress (GFDS.HCT116 and HCT116b cells were transfected with green fluorescence protein and subcutaneously injected into BALB/c nude male mice. Once xenografts were established, they were excised and orthotopically implanted into other male BALB/c nude mice using microsurgical techniques. Animal tissues were studied for metastases using histochemical techniques. Microarray analysis was performed to generate gene signatures associated with each subline. In vitro assessment of growth factor signaling pathway was performed under GFDS for 3 and 5 days.Both HCT116 and HCT116b iso-clonal variants demonstrated 100% primary tumor growth, invasion and peritoneal spread. However, HCT116 was highly metastatic with 68% metastasis observed in liver and/or lungs compared to 4% in HCT116b. Microarray analysis revealed an upregulation of survival and metastatic genes in HCT116 cells compared to HCT116b cells. In vitro analysis showed that HCT116 upregulated survival and migratory signaling proteins and downregulated apoptotic agents under GFDS. However, HCT116b cells effectively showed the opposite response under stress inducing cell death.We demonstrate the importance of clonal variation in determining metastatic potential of colorectal cancer cells using the HCT116/HCT116b iso-clonal variants in an orthotopic metastatic mouse model. Determination of clonal heterogeneity in patient tumors

  13. Secondary neoplasms of the larynx from a colonic adenocarcinoma

    DEFF Research Database (Denmark)

    Dadkhah, Naser; Hahn, Christoffer

    2015-01-01

    Secondary neoplasms of the larynx are rare and account for 0.09-0,4% of all laryngeal tumours. Cutaneous melanomas are the preponderant primaries metastasizing to the larynx, fol-lowed by renal cell carcinomas, breast and lung carcinomas. Colonic adenocarcinoma metastases to the larynx are extrem......Secondary neoplasms of the larynx are rare and account for 0.09-0,4% of all laryngeal tumours. Cutaneous melanomas are the preponderant primaries metastasizing to the larynx, fol-lowed by renal cell carcinomas, breast and lung carcinomas. Colonic adenocarcinoma metastases to the larynx...

  14. Comparative effects of RRR-alpha- and RRR-gamma-tocopherol on proliferation and apoptosis in human colon cancer cell lines

    Directory of Open Access Journals (Sweden)

    Sherman Devin

    2006-01-01

    Full Text Available Abstract Background Mediterranean societies, with diets rich in vitamin E isoforms, have a lower risk for colon cancer than those of northern Europe and the Americas. Vitamin E rich diets may neutralize free radicals generated by fecal bacteria in the gut and prevent DNA damage, but signal transduction activities can occur independent of the antioxidant function. The term vitamin E represents eight structurally related compounds, each differing in their potency and mechanisms of chemoprevention. The RRR-γ-tocopherol isoform is found primarily in the US diet, while RRR-α-tocopherol is highest in the plasma. Methods The effectiveness of RRR-α- and RRR-γ-tocopherol at inhibiting cell growth and inducing apoptosis in colon cancer cell lines with varying molecular characteristics (SW480, HCT-15, HCT-116 and HT-29 and primary colon cells (CCD-112CoN, nontransformed normal phenotype was studied. Colon cells were treated with and without RRR-α- or RRR-γ-tocopherol using varying tocopherol concentrations and time intervals. Cell proliferation and apoptosis were measured using the trypan blue assay, annexin V staining, DNA laddering and caspase activation. Results Treatment with RRR-γ-tocopherol resulted in significant cell death for all cancer cell lines tested, while RRR-α-tocopherol did not. Further, RRR-γ-tocopherol treatment showed no cytotoxicity to normal colon cells CCD-112CoN at the highest concentration and time point tested. RRR-γ-tocopherol treatment resulted in cleavage of PARP, caspase 3, 7, and 8, but not caspase 9. Differences in the percentage cell death and apoptosis were observed in different cell lines suggesting that molecular differences in these cell lines may influence the ability of RRR-γ-tocopherol to induce cell death. Conclusion This is the first study to demonstrate that multiple colon cancer cell lines containing varying genetic alterations will under go growth reduction and apoptosis in the presence of RRR

  15. Keratin 7 expression in lymph node metastases but not in the primary tumour correlates with distant metastases and poor prognosis in colon carcinoma

    Directory of Open Access Journals (Sweden)

    Piotr Czapiewski

    2016-11-01

    Full Text Available Colorectal carcinoma (CRC is one of the leading causes of cancer-related deaths worldwide. Alterations in keratin expression, including keratin 7 (K7, are frequent findings in multiple cancers, and they constitute a prognostic factor. The aim of our study was to evaluate the prognostic significance of K7 in the primary tumour and lymph node metastases in two separate cohorts of patients: the first one with lymph node involvement (LN+, 129 cases and the second one free of LN metastases (LN–, 85 cases. Keratin 7 expression in CRC was analysed on tissue microarrays with immunohistochemistry and evaluated using the h-score. In the LN+ group K7 positivity was identified in 7/129 (5.4% of primary tumours (PT and lymph node metastases (LNM; concordance between them was 94% ( 0.396. Keratin 7 was expressed in 8/85 cases (9.4% in the LN– group. K7 expression in LNM of the LN+ cohort correlated with shorter overall survival (OS (p = 0.047 and presence of distant metastases at diagnosis (p = 0.005. Expression of K7 in the primary tumour in both cohorts did not correlate with survival. We conclude that the status of K7 expression in metastatic lymph nodes from CRC is a poor prognostic factor.

  16. Modified Liver Hanging Maneuver for En-bloc Right-sided Hepatectomy Combined with Total Caudate Lobectomy for Colon-Cancer Liver Metastasis and Hepatocellular Carcinoma.

    Science.gov (United States)

    Hiroshima, Yukihiko; Matsuo, Kenichi; Kawaguchi, Daisuke; Kikuchi, Yutaro; Endo, Itaru; Koda, Keiji; Togo, Shinji; Hoffman, Robert M; Tanaka, Kuniya

    2016-04-01

    A right-sided hepatectomy with total caudate lobectomy is indicated for colorectal-cancer liver metastases (CLM) and hepatocellular carcinomas (HCC) located in the caudate lobe with extension to the right lobe of the liver. Caudate-lobe resection (i.e. segmentectomy 1 according to the Brisbane terminology) is one of the most difficult types of hepatectomy to carry out radically and safely. The deep portion of hepatic transection around the caudate lobe, hepatic veins and inferior vena cava is a critical source of massive bleeding. Prolonged transection can increase blood loss. We analyzed the outcome of 10 patients who underwent right-sided hepatectomy with caudate lobectomy using a modified liver hanging maneuver (mLHM) in comparison with 16 patients who underwent the operation without mLHM. Blood loss during liver transection and blood loss per unit area of cut surface were significantly less in the mLHM group (p=0.014 and 0.015, respectively). In patients diagnosed pathologically with liver impairment, transection time was significantly shorter in the mLHM group (p=0.038), as were red blood cell transfusion volume (p=0.042) and blood loss (p=0.049) during transection. Use of mLHM can potentially improve surgical outcomes by reducing blood loss and transection time, which are especially important for patients with liver impairment. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  17. Evidence based medicine (EBM) and evidence based radiology (EBR) in the follow-up of the patients after surgery for lung and colon-rectal carcinoma; Medicina basata sulle evidenze (EMB) e radiologia basata sulle evidenze (EBR) nel follow-up dei pazienti operati per tumore del polmone e del colon

    Energy Technology Data Exchange (ETDEWEB)

    Giovagnoni, Andrea; Ottaviani, Letizia; Mensa' , Anna; Durastanti, Martina; Floriani, Irene; Cascinu, Stefano [Marche Univ., Ancona (Italy). Azienda ospedaliera Umberto I, Istituto di radiologia, oncologia clinica

    2005-04-01

    considerare attendibili 9 lavori sui 41 selezionati. La maggior parte dei lavori (7/9) e le linee guida delle maggiori Societa Scientifiche Internazionali mostrano concordanza nel definire come non significativo il vantaggio clinico del follow up strumentale dei pazienti operati per tumore del polmone e colon. Ne consegue che esiste una enorme discrepanza tra i costi reali sostenuti nel follow up dei 40 pazienti osservati rispetto ai costi teorici estrapolati dalle raccomandazioni delle linee guida (surplus del 99.06% per il carcinoma del polmone e 93.6% per il carcinoma del colon). Conclusioni: I dati emersi consentono di aprire una discussione sul reale ruolo della radiologia nel follow-up dei pazienti neoplastici al fine di una piu oppotuna razionalizzazione delle ri0011sor.

  18. Phototoxic action of a zinc(II) phthalocyanine encapsulated into poloxamine polymeric micelles in 2D and 3D colon carcinoma cell cultures.

    Science.gov (United States)

    Chiarante, Nicolás; García Vior, María C; Awruch, Josefina; Marino, Julieta; Roguin, Leonor P

    2017-05-01

    Photodynamic therapy is emerging as a hopeful method for the treatment of oncological diseases. In the search of novel therapeutic strategies for colorectal cancer, in this work we reported the photocytotoxic activity of a lipophilic zinc(II) phthalocyanine on a murine colon adenocarcinoma cell line (CT26 cells). The 2,9(10),16(17),23(24) tetrakis[(2-dimethylamino)ethylsulfanyl]phthalocyaninatozinc(II), named Pc9, was encapsulated into Tetronic® 1107 polymeric poloxamine micelles (T1107) and assayed in 2D and 3D cell cultures. We showed that the formulation Pc9-T1107 was efficient to reduce cell viability after photodynamic treatment both in 2D cultures (IC50 10±2nM) as well as in CT26 spheroids (IC50 370±11nM). Cellular uptake of Pc9-T1107 was a time- and concentration-dependent process, being the phthalocyanine formulation mainly incorporated into lysosomal vesicles and endoplasmic reticulum cisterns, but not in mitochondria. Pc9-T1107 also induced the formation of reactive oxygen species immediately after cell irradiation. We also found that the phototoxic action of Pc9-T1107 was partially reversed in the presence of antioxidants, such as TROLOX and N-acetyl-cysteine. In addition, we showed that Pc9-T1107 treatment triggered an apoptotic cell death, as suggested by the detection of pyknotic nuclei, the reduction in the expression levels of procaspase-3 and the increase in caspase-3 enzymatic activity. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Flavokawain C Inhibits Cell Cycle and Promotes Apoptosis, Associated with Endoplasmic Reticulum Stress and Regulation of MAPKs and Akt Signaling Pathways in HCT 116 Human Colon Carcinoma Cells.

    Directory of Open Access Journals (Sweden)

    Chung-Weng Phang

    Full Text Available Flavokawain C (FKC is a naturally occurring chalcone which can be found in Kava (Piper methysticum Forst root. The present study evaluated the effect of FKC on the growth of various human cancer cell lines and the underlying associated mechanisms. FKC showed higher cytotoxic activity against HCT 116 cells in a time- and dose-dependent manner in comparison to other cell lines (MCF-7, HT-29, A549 and CaSki, with minimal toxicity on normal human colon cells. The apoptosis-inducing capability of FKC on HCT 116 cells was evidenced by cell shrinkage, chromatin condensation, DNA fragmentation and increased phosphatidylserine externalization. FKC was found to disrupt mitochondrial membrane potential, resulting in the release of Smac/DIABLO, AIF and cytochrome c into the cytoplasm. Our results also revealed that FKC induced intrinsic and extrinsic apoptosis via upregulation of the levels of pro-apoptotic proteins (Bak and death receptors (DR5, while downregulation of the levels of anti-apoptotic proteins (XIAP, cIAP-1, c-FlipL, Bcl-xL and survivin, resulting in the activation of caspase-3, -8 and -9 and cleavage of poly(ADP-ribose polymerase (PARP. FKC was also found to cause endoplasmic reticulum (ER stress, as suggested by the elevation of GADD153 protein after FKC treatment. After the cells were exposed to FKC (60μM over 18hrs, there was a substantial increase in the phosphorylation of ERK 1/2. The expression of phosphorylated Akt was also reduced. FKC also caused cell cycle arrest in the S phase in HCT 116 cells in a time- and dose-dependent manner and with accumulation of cells in the sub-G1 phase. This was accompanied by the downregulation of cyclin-dependent kinases (CDK2 and CDK4, consistent with the upregulation of CDK inhibitors (p21Cip1 and p27Kip1, and hypophosphorylation of Rb.

  20. EphB3-targeted regulation of miR-149 in the migration and invasion of human colonic carcinoma HCT116 and SW620 cells.

    Science.gov (United States)

    Zhang, Guodong; Liu, Xiaozhu; Li, Yinfeng; Wang, Yan; Liang, Huankun; Li, Kangyan; Li, Laiqing; Chen, Cuicui; Sun, Wenqiao; Ren, Shoulei; Zhu, Pengfei; Zhang, Licheng

    2017-03-01

    microRNAs play key roles during various crucial cell processes such as proliferation, migration, invasion and apoptosis. Also, microRNAs have been shown to possess oncogenic and tumor-suppressive functions in human cancers. Here, we describe the regulation and function of miR-149 in colorectal cancer cell lines. miR-149 expression patterns were detected in human colorectal cell lines and tissue samples, and then focused on its role in regulation of cell growth, migration, invasion, and its target gene identification. Furthermore, the function of the target gene of miR-149 was analyzed in vitro and in vivo. miR-149 expression was downregulated in human colorectal cancer HCT116 and SW620 cell lines compared to the normal colon epithelial NCM460 cell line using quantitative real-time polymerase chain reaction methods. Further studies indicated that introduction of miR-149 was able to suppress cell migration and invasion. Then, EphB3 was identified as a direct target gene of miR-149 in colorectal cancer cells. Moreover, experiments in vitro showed that knockdown expression of EphB3 could suppress cell proliferation and invasion, and ectopic expression of EphB3 restored the phenotypes of CRC cell lines transfected with miR149. In addition, silencing of EphB3 significantly affected cycle progression distribution and increased apoptosis in CRC cell lines. Finally, in vivo results demonstrated that knockdown of EphB3 by siRNA inhibited tumor growth. In conclusion,the important role of miR-149 in colorectal cancer progression suggesting that miR-149 may serve as a therapeutic target for colorectal cancer treatment. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  1. Cancer progression mediated by horizontal gene transfer in an in vivo model.

    Science.gov (United States)

    Trejo-Becerril, Catalina; Pérez-Cárdenas, Enrique; Taja-Chayeb, Lucía; Anker, Philippe; Herrera-Goepfert, Roberto; Medina-Velázquez, Luis A; Hidalgo-Miranda, Alfredo; Pérez-Montiel, Delia; Chávez-Blanco, Alma; Cruz-Velázquez, Judith; Díaz-Chávez, José; Gaxiola, Miguel; Dueñas-González, Alfonso

    2012-01-01

    It is known that cancer progresses by vertical gene transfer, but this paradigm ignores that DNA circulates in higher organisms and that it is biologically active upon its uptake by recipient cells. Here we confirm previous observations on the ability of cell-free DNA to induce in vitro cell transformation and tumorigenesis by treating NIH3T3 recipient murine cells with serum of colon cancer patients and supernatant of SW480 human cancer cells. Cell transformation and tumorigenesis of recipient cells did not occur if serum and supernatants were depleted of DNA. It is also demonstrated that horizontal cancer progression mediated by circulating DNA occurs via its uptake by recipient cells in an in vivo model where immunocompetent rats subjected to colon carcinogenesis with 1,2-dimethylhydrazine had increased rate of colonic tumors when injected in the dorsum with human SW480 colon carcinoma cells as a source of circulating oncogenic DNA, which could be offset by treating these animals with DNAse I and proteases. Though the contribution of biologically active molecules other than DNA for this phenomenon to occur cannot be ruled out, our results support the fact that cancer cells emit into the circulation biologically active DNA to foster tumor progression. Further exploration of the horizontal tumor progression phenomenon mediated by circulating DNA is clearly needed to determine whether its manipulation could have a role in cancer therapy.

  2. Capecitabine treatment of HCT-15 colon cancer cells induces ...

    African Journals Online (AJOL)

    15 colon carcinoma cells and investigate the underlying mechanism. Methods: Phase-contrast microscopy was used for the examination of morphological changes while flow cytometry was employed for the analysis of cell cycle distribution, ...

  3. In vitro migration of cytotoxic T lymphocyte derived from a colon carcinoma patient is dependent on CCL2 and CCR2.

    Science.gov (United States)

    Berencsi, Klara; Rani, Pyapalli; Zhang, Tianqian; Gross, Laura; Mastrangelo, Michael; Meropol, Neal J; Herlyn, Dorothee; Somasundaram, Rajasekharan

    2011-03-30

    Infiltration of colorectal carcinomas (CRC) with T-cells has been associated with good prognosis. There are some indications that chemokines could be involved in T-cell infiltration of tumors. Selective modulation of chemokine activity at the tumor site could attract immune cells resulting in tumor growth inhibition. In mouse tumor model systems, gene therapy with chemokines or administration of antibody (Ab)-chemokine fusion proteins have provided potent immune mediated tumor rejection which was mediated by infiltrating T cells at the tumor site. To develop such immunotherapeutic strategies for cancer patients, one must identify chemokines and their receptors involved in T-cell migration toward tumor cells. To identify chemokine and chemokine receptors involved in T-cell migration toward CRC cells, we have used our previously published three-dimensional organotypic CRC culture system. Organotypic culture was initiated with a layer of fetal fibroblast cells mixed with collagen matrix in a 24 well tissue culture plate. A layer of CRC cells was placed on top of the fibroblast-collagen layer which was followed by a separating layer of fibroblasts in collagen matrix. Anti-CRC specific cytotoxic T lymphocytes (CTLs) mixed with fibroblasts in collagen matrix were placed on top of the separating layer. Excess chemokine ligand (CCL) or Abs to chemokine or chemokine receptor (CCR) were used in migration inhibition assays to identify the chemokine and the receptor involved in CTL migration. Inclusion of excess CCL2 in T-cell layer or Ab to CCL2 in separating layer of collagen fibroblasts blocked the migration of CTLs toward tumor cells and in turn significantly inhibited tumor cell apoptosis. Also, Ab to CCR2 in the separating layer of collagen and fibroblasts blocked the migration of CTLs toward tumor cells and subsequently inhibited tumor cell apoptosis. Expression of CCR2 in four additional CRC patients' lymphocytes isolated from infiltrating tumor tissues suggests their

  4. Resveratrol suppresses IGF-1 induced human colon cancer cell proliferation and elevates apoptosis via suppression of IGF-1R/Wnt and activation of p53 signaling pathways

    Directory of Open Access Journals (Sweden)

    Radhakrishnan Sridhar

    2010-05-01

    Full Text Available Abstract Background Obesity is a global phenomenon and is associated with various types of cancer, including colon cancer. There is a growing interest for safe and effective bioactive compounds that suppress the risk for obesity-promoted colon cancer. Resveratrol (trans-3, 4', 5,-trihydroxystilbene, a stilbenoid found in the skin of red grapes and peanuts suppresses many types of cancers by regulating cell proliferation and apoptosis through a variety of mechanisms, however, resveratrol effects on obesity-promoted colon cancer are not clearly established. Methods We investigated the anti-proliferative effects of resveratrol on HT-29 and SW480 human colon cancer cells in the presence and absence of insulin like growth factor-1 (IGF-1; elevated during obesity and elucidated the mechanisms of action using IGF-1R siRNA in HT-29 cells which represents advanced colon carcinogenesis. Results Resveratrol (100-150 μM exhibited anti-proliferative properties in HT-29 cells even after IGF-1 exposure by arresting G0/G1-S phase cell cycle progression through p27 stimulation and cyclin D1 suppression. Treatment with resveratrol suppressed IGF-1R protein levels and concurrently attenuated the downstream Akt/Wnt signaling pathways that play a critical role in cell proliferation. Targeted suppression of IGF-1R using IGF-1R siRNA also affected these signaling pathways in a similar manner. Resveratrol treatment induced apoptosis by activating tumor suppressor p53 protein, whereas IGF-1R siRNA treatment did not affect apoptosis. Our data suggests that resveratrol not only suppresses cell proliferation by inhibiting IGF-1R and its downstream signaling pathways similar to that of IGF-1R siRNA but also enhances apoptosis via activation of the p53 pathway. Conclusions For the first time, we report that resveratrol suppresses colon cancer cell proliferation and elevates apoptosis even in the presence of IGF-1 via suppression of IGF-1R/Akt/Wnt signaling pathways and

  5. A mechanically-induced colon cancer cell population shows increased metastatic potential

    KAUST Repository

    Tang, Xin

    2014-05-29

    Background: Metastasis accounts for the majority of deaths from cancer. Although tumor microenvironment has been shown to have a significant impact on the initiation and/or promotion of metastasis, the mechanism remains elusive. We previously reported that HCT-8 colon cancer cells underwent a phenotypic transition from an adhesive epithelial type (E-cell) to a rounded dissociated type (R-cell) via soft substrate culture, which resembled the initiation of metastasis. The objective of current study was to investigate the molecular and metabolic mechanisms of the E-R transition.Methods: Global gene expressions of HCT-8 E and R cells were measured by RNA Sequencing (RNA-seq); and the results were further confirmed by real-time PCR. Reactive oxygen species (ROS), anoikis resistance, enzyme activity of aldehyde dehydrogenase 3 family, member A1 (ALDH3A1), and in vitro invasion assay were tested on both E and R cells. The deformability of HCT-8 E and R cells was measured by atomic force microscopy (AFM). To study the in vivo invasiveness of two cell types, athymic nude mice were intra-splenically injected with HCT-8 E or R cells and sacrificed after 9 weeks. Incidences of tumor development and metastasis were histologically evaluated and analyzed with Fisher\\'s exact test.Results: Besides HCT-8, E-R transition on soft substrates was also seen in three other cancer cell lines (HCT116, SW480 colon and DU145 prostate cancer). The expression of some genes, such as ALDH3A1, TNS4, CLDN2, and AKR1B10, which are known to play important roles in cancer cell migration, invasion, proliferation and apoptosis, were increased in HCT-8 R cells. R cells also showed higher ALDH3A1 enzyme activity, higher ROS, higher anoikis resistance, and higher softness than E cells. More importantly, in vitro assay and in vivo animal models revealed that HCT-8 R cells were more invasive than E cells.Conclusions: Our comprehensive comparison of HCT-8 E and R cells revealed differences of molecular

  6. Reduced migration of MLH1 deficient colon cancer cells depends on SPTAN1

    Science.gov (United States)

    2014-01-01

    Introduction Defects in the DNA mismatch repair (MMR) protein MLH1 are frequently observed in sporadic and hereditary colorectal cancers (CRC). Affected tumors generate much less metastatic potential than the MLH1 proficient forms. Although MLH1 has been shown to be not only involved in postreplicative MMR but also in several MMR independent processes like cytoskeletal organization, the connection between MLH1 and metastasis remains unclear. We recently identified non-erythroid spectrin αII (SPTAN1), a scaffolding protein involved in cell adhesion and motility, to interact with MLH1. In the current study, the interaction of MLH1 and SPTAN1 and its potential consequences for CRC metastasis was evaluated. Methods Nine cancer cell lines as well as fresh and paraffin embedded colon cancer tissue from 12 patients were used in gene expression studies of SPTAN1 and MLH1. Co-expression of SPTAN1 and MLH1 was analyzed by siRNA knock down of MLH1 in HeLa, HEK293, MLH1 positive HCT116, SW480 and LoVo cells. Effects on cellular motility were determined in MLH1 deficient HCT116 and MLH1 deficient HEK293T compared to their MLH1 proficient sister cells, respectively. Results MLH1 deficiency is clearly associated with SPTAN1 reduction. Moreover, siRNA knock down of MLH1 decreased the mRNA level of SPTAN1 in HeLa, HEK293 as well as in MLH1 positive HCT116 cells, which indicates a co-expression of SPTAN1 by MLH1. In addition, cellular motility of MLH1 deficient HCT116 and MLH1 deficient HEK293T cells was impaired compared to the MLH1 proficient sister clones. Consequently, overexpression of SPTAN1 increased migration of MLH1 deficient cells while knock down of SPTAN1 decreased cellular mobility of MLH1 proficient cells, indicating SPTAN1-dependent migration ability. Conclusions These data suggest that SPTAN1 levels decreased in concordance with MLH1 reduction and impaired cellular mobility in MLH1 deficient colon cancer cells. Therefore, aggressiveness of MLH1-positive CRC might be

  7. A mechanically-induced colon cancer cell population shows increased metastatic potential.

    Science.gov (United States)

    Tang, Xin; Kuhlenschmidt, Theresa B; Li, Qian; Ali, Shahjahan; Lezmi, Stephane; Chen, Hong; Pires-Alves, Melissa; Laegreid, William W; Saif, Taher A; Kuhlenschmidt, Mark S

    2014-05-29

    Metastasis accounts for the majority of deaths from cancer. Although tumor microenvironment has been shown to have a significant impact on the initiation and/or promotion of metastasis, the mechanism remains elusive. We previously reported that HCT-8 colon cancer cells underwent a phenotypic transition from an adhesive epithelial type (E-cell) to a rounded dissociated type (R-cell) via soft substrate culture, which resembled the initiation of metastasis. The objective of current study was to investigate the molecular and metabolic mechanisms of the E-R transition. Global gene expressions of HCT-8 E and R cells were measured by RNA Sequencing (RNA-seq); and the results were further confirmed by real-time PCR. Reactive oxygen species (ROS), anoikis resistance, enzyme activity of aldehyde dehydrogenase 3 family, member A1 (ALDH3A1), and in vitro invasion assay were tested on both E and R cells. The deformability of HCT-8 E and R cells was measured by atomic force microscopy (AFM). To study the in vivo invasiveness of two cell types, athymic nude mice were intra-splenically injected with HCT-8 E or R cells and sacrificed after 9 weeks. Incidences of tumor development and metastasis were histologically evaluated and analyzed with Fisher's exact test. Besides HCT-8, E-R transition on soft substrates was also seen in three other cancer cell lines (HCT116, SW480 colon and DU145 prostate cancer). The expression of some genes, such as ALDH3A1, TNS4, CLDN2, and AKR1B10, which are known to play important roles in cancer cell migration, invasion, proliferation and apoptosis, were increased in HCT-8 R cells. R cells also showed higher ALDH3A1 enzyme activity, higher ROS, higher anoikis resistance, and higher softness than E cells. More importantly, in vitro assay and in vivo animal models revealed that HCT-8 R cells were more invasive than E cells. Our comprehensive comparison of HCT-8 E and R cells revealed differences of molecular, phenotypical, and mechanical signatures

  8. Synthesis, structural and spectroscopic characterization, in vitro cytotoxicity and in vivo activity as free radical scavengers of chlorido(p-cymene) complexes of ruthenium(II) containing N-alkylphenothiazines.

    Science.gov (United States)

    Krstić, Milena; Sovilj, Sofija P; Grgurić-Šipka, Sanja; Evans, Ivana Radosavljević; Borozan, Sunčica; Santibanez, Juan Francisco

    2011-09-01

    Three new ruthenium(II) complexes 1-3 containing N-alkylphenothiazine molecules were synthesized by reaction of [RuCl(2)(η(6)-p-cymene)](2) with chlorpromazine hydrochloride (1), trifluoperazine dihydrochloride (2) or thioridazine hydrochloride (3). The compounds of the general formula L[RuCl(3)(η(6)-p-cymene)] were characterized by elemental analysis and spectroscopic methods (FT-IR, UV-Vis, (1)H and (13)C NMR). Complex 2 was structurally characterized by single crystal X-ray diffraction. In vitro cytotoxic activity of complexes 1-3 were assayed in four human carcinoma cell lines MCF-7, MDA-MB-453 (breast carcinoma), SW-480 (colon carcinoma) and IM9 (myeloma multiple cells). The highest cytotoxicity (12.1 ≤ IC(50) ≤ 17.3 μM) and induced a total (SW-480) or almost total cell death (MCF-7, MDA-MB-453) at 25 μM in 48 h of treatment were observed for complex 2. The influence of three different doses (0.4, 4.5 and 90.4 μM/kg bw) of complex 2 on activities of antioxidants enzymes (superoxide dismutase (SOD) and catalase (CAT)) and lactate dehydrogenase (LDH) were investigated under physiological conditions. The effects on nitrite production (NO(2)(-)) and level of erythrocytes malondialdehyde (MDA) in rats blood were evaluated, too. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  9. Endoskopisk mucosaresektion i colon og rectum

    DEFF Research Database (Denmark)

    Malmstrom, M.L.; Meisner, S.

    2008-01-01

    EMR (endoscopic mucosal resection) is an endoscopic procedure where benign adenomas and superficial carcinomas can be removed from the gastrointestinal tract. The method is an alternative to laparoscopic and open surgery. This paper focuses on lesions of the colon and rectum, presenting the metho...

  10. Muscarinic Receptor Signaling in Colon Cancer

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-03-02

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

  11. Muscarinic Receptor Signaling in Colon Cancer

    Directory of Open Access Journals (Sweden)

    Jean-Pierre Raufman

    2011-03-01

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

  12. Verrucous carcinoma at ileostomy site

    OpenAIRE

    Dhakre, Vijay; Nagral, Sanjay

    2017-01-01

    ABSTRACT We describe of a case, a 50 year old male who was operated for carcinoma of the descending colon and diverting loop ileostomy, developed a fungating lesion in mucocutaneous junction of ileostomy after one year which on histology revealed to be a Verrucous carcinoma. RESUMO Descrevemos um caso, homem, 50 anos, que foi operado para carcinoma de cólon descendente e ileostomia em alça para desvio. Transcorrido um ano, o paciente desenvolveu uma lesão vegetante na junção mucocutânea da...

  13. NUBPL, a novel metastasis-related gene, promotes colorectal carcinoma cell motility by inducing epithelial-mesenchymal transition.

    Science.gov (United States)

    Wang, Yuhui; Wu, Nan; Sun, Donglin; Sun, Haiming; Tong, Dandan; Liu, Duo; Pang, Bo; Li, Su; Wei, Jia; Dai, Jialin; Liu, Yang; Bai, Jing; Geng, Jingshu; Fu, Songbin; Jin, Yan

    2017-06-01

    Nucleotide binding protein-like, NUBPL, is an assembly factor for human mitochondrial complex I, which is the biggest member of the mitochondrial respiratory chain. However, the relationship between NUBPL and carcinoma progression remains unknown. In this study, NUBPL was characterized for its role in colorectal cancer (CRC) and the underlying molecular mechanisms. Data (n = 197) from the Oncomine database revealed that mRNA levels of NUBPL were remarkably overexpressed in CRC tissues compared with normal tissues. In addition, immunohistochemical analysis of 75 pairs of CRC and non-tumor tissues showed that the expression level of NUBPL was significantly higher in CRC tissues, and its expression level was positively associated with lymph node metastasis (P = 0.028) and advanced staging (P = 0.030). Expression of NUBPL in metastatic lymph nodes of CRC patients was also detected by immunohistochemical staining and high expression levels of NUBPL were observed. Overexpression of NUBPL significantly promoted the migration and invasion ability of CRC cell lines SW480 and SW620, whereas knockdown of NUBPL lead to an opposite effect. Our further study found that NUBPL could induce epithelial-mesenchymal transition (EMT), characterized by downregulation of epithelial markers (E-cadherin) and upregulation of mesenchymal markers (N-cadherin and vimentin). Moreover, NUBPL was able to activate ERK, which is believed to promote EMT and tumor metastasis. Inhibition of ERK suppressed the NUBPL-induced changes in EMT and cell motility. These data showed that NUBPL plays a vital role in CRC migration and invasion by inducing EMT and activating ERK. It might be a novel therapeutic target for CRC. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  14. Expression of metallothionein in dimethylhydrazine-induced colonic precancerous and cancerous model in rat

    Directory of Open Access Journals (Sweden)

    Pamela Christudoss

    2016-01-01

    Conclusion: This study suggests that a decrease in the colonic MT mRNA expression, MT protein expression, and content in DMH-induced colonic cancer model is associated with the development of preneoplastic lesions and further progression to carcinoma in the colon results in a greater reduction in the levels of each of these parameters.

  15. Epigenetic silencing of serine protease HTRA1 drives polyploidy.

    Science.gov (United States)

    Schmidt, Nina; Irle, Inga; Ripkens, Kamilla; Lux, Vanda; Nelles, Jasmin; Johannes, Christian; Parry, Lee; Greenow, Kirsty; Amir, Sarah; Campioni, Mara; Baldi, Alfonso; Oka, Chio; Kawaichi, Masashi; Clarke, Alan R; Ehrmann, Michael

    2016-07-07

    Increased numbers and improperly positioned centrosomes, aneuploidy or polyploidy, and chromosomal instability are frequently observed characteristics of cancer cells. While some aspects of these events and the checkpoint mechanisms are well studied, not all players have yet been identified. As the role of proteases other than the proteasome in tumorigenesis is an insufficiently addressed question, we investigated the epigenetic control of the widely conserved protease HTRA1 and the phenotypes of deregulation. Mouse embryonal fibroblasts and HCT116 and SW480 cells were used to study the mechanism of epigenetic silencing of HTRA1. In addition, using cell biological and genetic methods, the phenotypes of downregulation of HTRA1 expression were investigated. HTRA1 is epigenetically silenced in HCT116 colon carcinoma cells via the epigenetic adaptor protein MBD2. On the cellular level, HTRA1 depletion causes multiple phenotypes including acceleration of cell growth, centrosome amplification and polyploidy in SW480 colon adenocarcinoma cells as well as in primary mouse embryonic fibroblasts (MEFs). Downregulation of HTRA1 causes a number of phenotypes that are hallmarks of cancer cells suggesting that the methylation state of the HtrA1 promoter may be used as a biomarker for tumour cells or cells at risk of transformation.

  16. Iatrogenic Colonic Perforation due to Computed Tomographic Colonography

    Directory of Open Access Journals (Sweden)

    Takashi Kato

    2015-05-01

    Full Text Available Although the complications of computed tomographic colonography (CTC are very rare, CTC is associated with potential risk of colonic perforation. In the present report we describe two cases of colonic perforation secondary to CTC. In the first case with ascending colonic carcinoma, insertion of a rigid double-balloon catheter caused direct rectal wall perforation. In the second case with obstructive colonic carcinoma, pneumoperitoneum developed due to automated carbon dioxide insufflation. Both patients were asymptomatic after examination and recovered without any complications. Based on the findings of the current cases, we recommend that a soft-tip catheter be used for CTC, and suggest that colonic perforation can occur even with automatic insufflation, depending on patient characteristics.

  17. Application of colon interposition among the esophageal cancer patients with partial gastrectomy.

    Science.gov (United States)

    Chen, Qiuqiang; Mao, Weimin; Yu, Huanming; Liang, Yixian; Wang, Jiane; Chen, Guoping

    2016-12-01

    Esophageal reconstruction with colon interposition is an alternative solution for the esophageal cancer patients who have partial gastrectomy. The aim of this study was to investigate the therapeutic effects of colon interposition among the esophageal carcinoma patients with partial gastrectomy. Under institutional review board approval, 32 esophageal carcinoma patients with a history of partial gastrectomy were included in this study. All the patients had been diagnosed and confirmed squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma by histopathological examination. Surgical approaches, complications and therapeutic results were analyzed in the current study. Thirty-two esophageal carcinoma patients (29 men, 3 women, median age 63.2 years) were included in this study. Isoperistaltic colon interposition was carried out on 14 patients; their 1-year and 2-year survival rate was 92.9% and 78.6%, respectively. Antiperistaltic colon interposition was carried out on 18 patients; their 1-year and 2-year survival rate was 88.9% and 77.8%, respectively. In which, cervical anastomotic leakage was observed on six patients. Colon interposition is an ideal surgical approach for the esophageal carcinoma patients who had partial gastrectomy. Isoperistaltic colon interposition is preferred, but antiperistaltic colon interposition has the advantage that a longer colon can be used.

  18. MicroRNA-32 (miR-32) regulates phosphatase and tensin homologue (PTEN) expression and promotes growth, migration, and invasion in colorectal carcinoma cells

    Science.gov (United States)

    2013-01-01

    Background Colorectal carcinoma (CRC) is one of the leading causes of cancer-related mortality worldwide. MicroRNAs (miRNAs, miRs) play important roles in carcinogenesis. MiR-32 has been shown to be upregulated in CRC. In this study, we identified the potential effects of miR-32 on some important biological properties of CRC cells, and clarified the regulation of PTEN by miR-32. Methods The effect of miR-32 on PTEN expression was assessed in CRC cell lines with miR-32 mimics/inhibitor to increase/decrease miR-32 expression. Furthermore, the roles of miR-32 in regulating CRC cells biological properties were analyzed with miR-32 mimics/inhibitor-transfected cells. The 3′-untranslated region (3′-UTR) of PTEN combined with miR-32 was verified by dual-luciferase reporter assay. Results Gain-of-function and loss-of-function studies showed that overexpression of miR-32 promoted SW480 cell proliferation, migration, and invasion, reduced apoptosis, and resulted in downregulation of PTEN at a posttranscriptional level. However, miR-32 knock-down inhibited these processes in HCT-116 cells and enhanced the expression of PTEN protein. In addition, we further identified PTEN as the functional downstream target of miR-32 by directly targeting the 3′-UTR of PTEN. Conclusions Our results demonstrated that miR-32 was involved in tumorigenesis of CRC at least in part by suppression of PTEN. PMID:23617834

  19. Colonic adenocarcinoma presenting as hemophagocytic syndrome

    Directory of Open Access Journals (Sweden)

    Murtaza Ali

    2017-01-01

    Full Text Available Hemophagocytic syndrome (hemophagocytic lymphohistiocytosis [HLH] is a rare and potentially fatal disorder characterized by pathological immune activation associated with primary familial disorder, genetic mutation or occurring as a sporadic condition. The later can be secondary to infections, malignancies, or autoimmune diseases. Malignancy-associated HLH is commonly seen in hematological malignancies and rarely with solid organ tumors. We report a case of adenocarcinoma colon presenting as hemophagocytic syndrome. To the best of our knowledge, it is the first case report of HLH secondary to carcinoma colon.

  20. Thymic carcinoma

    Directory of Open Access Journals (Sweden)

    Vitória Homem Machado

    2016-10-01

    Full Text Available Thymic carcinomas are a heterogeneous group of aggressive, invasive epithelial malignancies. Their incidence is rare, occurring predominantly in middle-aged men. Here we present the typical imaging findings of a thymic carcinoma. The combination of imaging characteristics with tumor location and patient age provides a roadmap for approaching the differential diagnosis. Keywords: Thymus Gland; carcinoma; mediastinal neoplasms

  1. In vitro and in vivo anti-colon cancer effects of Garcinia mangostana xanthones extract

    National Research Council Canada - National Science Library

    Aisha, Abdalrahim F A; Abu-Salah, Khalid M; Ismail, Zhari; Majid, Amin Malik Shah Abdul

    2012-01-01

    .... mangostana fruit rinds and was analyzed by LC-MS. Anti-colon cancer effect was investigated on HCT 116 human colorectal carcinoma cells including cytotoxicity, apoptosis, anti-tumorigenicity, and effect on cell signalling pathways...

  2. Parotid carcinoma

    DEFF Research Database (Denmark)

    Sørensen, Kristine Bjørndal; Godballe, Christian; de Stricker, Karin

    2006-01-01

    OBJECTIVES: Our aim is to investigate the expression of kit protein (KIT) and epidermal growth factor receptor (EGFR) in parotid carcinomas in order to correlate the expression to histology and prognosis. Further we want to perform mutation analysis of KIT-positive adenoid cystic carcinomas....... PATIENTS AND METHODS: Formalin-fixed paraffin-embedded sections from 73 patients with parotid gland carcinomas were used for the study. The sections were stained with both KIT and EGFR polyclonal antibodies. Twelve KIT-positive adenoid cystic carcinomas were examined for c-kit mutation in codon 816....... RESULTS: Of all carcinomas 25% were KIT-positive and 79% were EGFR-positive. Ninety-two percentage of the adenoid cystic carcinomas were KIT-positive. None of the adenoid cystic carcinomas had mutations in codon 816 of the c-kit gene. CONCLUSION: Neither KIT- nor EGFR-expression seem to harbour...

  3. Anorectal carcinoma involving the female genital tract: the morbidity ...

    African Journals Online (AJOL)

    Background: Carcinoma of the colon and anorectum affect a younger age group in Africans, and patients often present late with advanced disease. Method: A retrospective review of 22 females treated for anorectal carcinoma. Results: Fourteen females had genital tract involvement; their mean age was 33.8 years. Thirteen ...

  4. Giant sigmoid diverticulum with coexisting metastatic rectal carcinoma: a case report.

    LENUS (Irish Health Repository)

    Sasi, Walid

    2010-01-01

    Giant diverticulum of the colon is a rare but clinically significant condition, usually regarded as a complication of an already existing colonic diverticular disease. This is the first report of a giant diverticulum of the colon with a co-existing rectal carcinoma.

  5. Early stage colon cancer

    National Research Council Canada - National Science Library

    Freeman, Hugh James

    2013-01-01

    .... After resection of malignant pedunculated colon polyps or early stage colon cancers, long-term repeated surveillance programs can also lead to detection and removal of asymptomatic high risk advanced...

  6. Colon diverticula - slideshow

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/presentations/100158.htm Colon diverticula - series—Normal anatomy To use the sharing ... to slide 6 out of 6 Overview The colon, or large intestine, is a muscular tube that ...

  7. Colon cancer - slideshow

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/presentations/100157.htm Colon cancer - Series—Normal anatomy To use the sharing ... to slide 5 out of 5 Overview The colon, or large intestine, is a muscular tube that ...

  8. Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4

    NARCIS (Netherlands)

    Todaro, Matilde; Alea, Mileidys Perez; Di Stefano, Anna B.; Cammareri, Patrizia; Vermeulen, Louis; Iovino, Flora; Tripodo, Claudio; Russo, Antonio; Gulotta, Gaspare; Medema, Jan Paul; Stassi, Giorgio

    2007-01-01

    A novel paradigm in tumor biology suggests that cancer growth is driven by stem-like cells within a tumor. Here, we describe the identification and characterization of such cells from colon carcinomas using the stem cell marker CD133 that accounts around 2% of the cells in human colon cancer. The

  9. Disparities in quality of care for colon cancer between hospitals in the Netherlands

    NARCIS (Netherlands)

    Elferink, M.A.G.; Wouters, M.W.J.M.; Krijnen, P.; Lemmens, V.E.P.P.; Jansen-Landheer, M.L.E.A.; van de Velde, C.J.H.; Siesling, Sabine; Tollenaar, R.A.E.M.

    2010-01-01

    Background: Aim of this study was to describe treatment patterns and outcome according to region, and according to hospital types and volumes among patients with colon cancer in the Netherlands. Methods: All patients with invasive colon carcinoma diagnosed in the period 2001–2006 were selected from

  10. Primary enteric-type adenocarcinomas of the urinary bladder are histogenetically analogous to colorectal carcinomas: Immunohistochemical evaluation of 109 cases

    Directory of Open Access Journals (Sweden)

    Saad S. Eissa

    2010-04-01

    In conclusion, primary non-urachal enteric-type adenocarcinoma of the urinary bladder is morphologically and immunophenotypically similar – if not identical – to colonic adenocarcinoma. The frequent association of enteric carcinomas of the urinary bladder with intestinal metaplasia and/or colonic-type adenomas with dysplasia suggests possible carcinogenetic pathways similar to that observed in colorectal carcinomas.

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

    OpenAIRE

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

    2014-01-01

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

  12. The Effects of Arsenic Trioxide on DNA Synthesis and Genotoxicity in Human Colon Cancer Cells

    OpenAIRE

    Christian Rogers; Tchounwou, Paul B.; Walker, Alice M.; Barbara Graham; Jacqueline J. Stevens

    2010-01-01

    Colon cancer is the third leading cause of cancer-related deaths worldwide. Recent studies in our laboratory have demonstrated that arsenic trioxide is cytotoxic in human colon cancer (HT-29), lung (A549) and breast (MCF-7) carcinoma cells. The purpose of the present study is to investigate the effects of arsenic trioxide on DNA synthesis and the possible genotoxic effects on human colon cancer cells. HT-29 cells were cultured according to standard protocol, followed by exposure to various do...

  13. intraoperative colonic irrigation in the management of left sided ...

    African Journals Online (AJOL)

    hi-tech

    2000-11-01

    Nov 1, 2000 ... Castrati G., Scotti M., Fiorone E. and Arrigoni G. L'intervento di Hartmann nelle lesioni complicate del retto sigma. Minerva. Chir. 1989; 44:1485-8. 30. Amsterdam E. and Krispin M. Primary resection with colocolostomy for obstructive carcinoma of the left side of the colon. Amer. J. Surg. 1985; 150:558-60.

  14. Basisquamous Carcinoma

    Directory of Open Access Journals (Sweden)

    Yesudian Devakar P

    1997-01-01

    Full Text Available A 50 year old woman presented with an ulceroproliferative mass in the value of 4 month duration. Biopsy of the lesion showed features of a basisquamous cell carcinoma. This is a rare tumour showing histopathological features of both basal cell and squamous cell carcinomas. The clinical, histopathological and histogenetic status of this tumour are discussed.

  15. Different molecular organization of two carotenoids, lutein and zeaxanthin, in human colon epithelial cells and colon adenocarcinoma cells

    Science.gov (United States)

    Grudzinski, Wojciech; Piet, Mateusz; Luchowski, Rafal; Reszczynska, Emilia; Welc, Renata; Paduch, Roman; Gruszecki, Wieslaw I.

    2018-01-01

    Two cell lines, human normal colon epithelial cells (CCD 841 CoTr) and human colon adenocarcinoma cells (HT-29) were cultured in the presence of exogenous carotenoids, either zeaxanthin or lutein. Both carotenoids demonstrated cytotoxicity with respect to cancer cells but not to normal cells. Cells from both the cell lines were analyzed with application of fluorescence lifetime imaging microscopy and Raman scattering microscopy. Both imaging techniques show effective incorporation of carotenoid molecules into growing cells. Comparison of the Raman scattering and fluorescence lifetime characteristics reveals different molecular organization of carotenoids in the carcinoma and normal cells. The main difference consists in a carotenoid aggregation level which is substantially lower in the carcinoma cells as compared to the normal cells. Different molecular organization of carotenoids was interpreted in terms of a different metabolism of normal and carcinoma cells and has been concluded to provide a possibility of cancer diagnosis based on spectroscopic analyses.

  16. Synthesis, characterization and cytotoxicity of palladium(II complex of 3-[(2-hydroxy-benzylidene-amino]-2-thioxo-imidazolidin-4-one

    Directory of Open Access Journals (Sweden)

    Šmit Biljana

    2013-01-01

    Full Text Available The polydentate ligand, 3-[(2-hydroxy-benzylidene-amino]-2-thioxo-imidazolidin-4-one, was synthesized by intermolecular cyclocondensation reaction of 2-hydroxybenzaldehyde thiosemicarbazone and ethylchloroacetate. Novel palladium(II complex was obtained by nucleophilic substitution of both DMSO ligands from cis-[Pd(DMSO2Cl2] with iminic nitrogen and thiolactamic sulfur from ligand. The structure of compounds was characterized on the basis of their spectral data. The cytotoxic activity of the ligand and palladium(II complex was studied on tumor cell lines: human colon carcinoma HCT-116 and SW-480 cells using MTT viability test. The results show that investigated palladium(II complex has significantly greater cytotoxic effect compared to ligand. [Projekat Ministarstva nauke Republike SRbije, br. 172011 and III41010

  17. Cytotoxic Biscembranoids from the Soft Coral Sarcophyton pauciplicatum.

    Science.gov (United States)

    Nam, Nguyen Hoai; Tung, Pham The; Ngoc, Ninh Thi; Hanh, Tran Thi Hong; Thao, Nguyen Phuong; Thanh, Nguyen Van; Cuong, Nguyen Xuan; Thao, Do Thi; Huong, Tran Thu; Thung, Do Cong; Kiem, Phan Van; Kim, Young Ho; Minh, Chau Van

    2015-01-01

    Ten biscembranoids (1-10), including the two new compounds sarcophytolides M and N (1 and 2), were isolated from the methanol extract of the Vietnamese soft coral Sarcophyton pauciplicatum. Their structures were elucidated by spectroscopic methods including one dimensional (1D)- and 2D-NMR, high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), and circular dichroism (CD). The in vitro cytotoxic activity of all isolated compounds against a panel of eight human cancer cell lines including HepG2 (hepatoma cancer), HL-60 (acute leukemia), KB (epidermoid carcinoma), LNCaP (prostate cancer), LU-1 (lung cancer), MCF7 (breast cancer), SK-Mel2 (melanoma), and SW480 (colon adenocarcinoma) was evaluated using the sulforhodamine B colorimetric assay. Among the isolated biscembranoids, 1, 3, 4, 7, 9, and 10 exhibited significant cytotoxic effects and may be selected for further studies of their anticancer activity.

  18. Diverticular disease of the right colon

    Directory of Open Access Journals (Sweden)

    Boutross-Tadross Odette

    2011-10-01

    Full Text Available Abstract Background The incidence of colonic diverticular disease varies with national origin, cultural background and diet. The frequency of this disease increases with advancing age. Right-sided diverticular disease is uncommon and reported to occur in 1-2% of surgical specimens in European and American series. In contrast the disease is more prevalent and reported in 43-50% of specimens in Asian series. Various lines of evidence suggest this variation may represent hereditary differences. The aim of the study is to report all cases of right sided diverticular disease underwent surgical resection or identified during pathological examination of right hemicoloectomy specimens Methods A retrospective review of all surgical specimens with right sided colonic diverticular disease selected from a larger database of all colonic diverticulosis and diverticulitis surgical specimen reported between January 1993 and December 2010 at the Pathology Department McMaster University Medical Centre Canada. The clinical and pathological features of these cases were reviewed Results The review identified 15 cases of right colon diverticulosis. The clinical diagnoses of these cases were appendicitis, diverticulitis or adenocarcinoma. Eight cases of single congenital perforated diverticuli were identified and seven cases were incidental multiple acquired diverticuli found in specimen resected for right side colonic carcinomas/large adenomas. Laparotomy or laparoscopic assisted haemicolectomies were done for all cases. Pathological examination showed caecal wall thickening with inflammation associated with perforated diverticuli. Histology confirmed true solitary diverticuli that exhibited in two cases thick walled vessels in the submucosa and muscular layer indicating vascular malformation/angiodysplasia. Acquired diverticuli tend to be multiple and are mostly seen in specimens resected for neoplastic right colon diseases. Conclusion Single true diverticular

  19. GALLBLADDER CARCINOMA

    Directory of Open Access Journals (Sweden)

    Blaž Trotovšek

    2003-12-01

    Full Text Available Background. Carcinoma of the gallbladder is a tumour with a dismal prognosis and 5-years overall survival rate less than 5%. Among the tumours of the gastrointestinal tract it is fifth in the row and its incidence is approximately 1.2/105. Tumour occurs more often (2–6 times in women and in people over 50 years old (90%. According to the Slovenian Registry of Cancer for year 1998 the incidence of gallbladder carcinoma was 2.7/105 and it occurred 4 times more often among women. The most important risk factors for development of gallbladder carcinoma are: bile stones, chronic inflammation and polyps of the gallbladder. Carcinoma of the gallbladder develops in only 2–3% of the patients with bile stones. When discovered, carcinoma has already invaded the liver in 60%, regional lymph nodes in 45% and the other surrounding organs in 40%. Carcinoma is at time of diagnosis already disseminated in distant organs in 20%. Only in 10% of the patients it is confined to the gallbladder wall. Before the routine use of the ultrasound, computed tomography and tumour markers the disease was discovered preoperatively in 10% versus 90% today. Diagnostic percutaneous biopsy is not recommended. TNM classification and staging of the disease is important for the decision of the modality of treatment.Conclusions. For TNM stage I gallbladder carcinoma, simple cholecystectomy is sufficient. When stage II-IVa is discovered, »en block« resection of gallbladder, liver segments 4b and 5, common bile duct and thorough lymphadenectomy is recommended. Regional radiotherapy and intraarterial chemotherapy with Mitomycin-C are showing promising results. Longterm outcome in patients with gallbladder carcinoma is improving but it is still disappointing.

  20. Tracheal Carcinoma

    Directory of Open Access Journals (Sweden)

    Ashok K Chauhan

    2012-01-01

    Full Text Available Adenoid cystic carcinoma of the trachea is a rare primary tracheal malignancy. Obstructive symptoms such as dyspnoea, hoarseness of voice, dysphasia are commonly seen symptoms. Combined modality treatments including surgery and radiation therapy are considered as optimal treatment for these tumours. A case of adenoid cystic carcinoma in a 35 years old male patient who was treated successfully by surgical excision and external beam radiation therapy is presented.

  1. Undifferentiated salivary gland carcinomas

    DEFF Research Database (Denmark)

    Herbst, H.; Hamilton-Dutoit, S.; Jakel, K.T.

    2004-01-01

    malignant lymphomas, amelanotic melanomas, Merkel cell carcinomas, and adenoid cystic carcinomas, in particular in small biopsy materials. Because of the rarity of undifferentiated salivary gland carcinomas, the differential diagnosis should always include metastases of undifferentiated carcinomas arising...

  2. Alteration of gene expression in macroscopically normal colonic mucosa from individuals with a family history of sporadic colon cancer.

    Science.gov (United States)

    Hao, Chun-Yi; Moore, Dan H; Wong, Patrick; Bennington, James L; Lee, Nancy M; Chen, Ling-Chun

    2005-02-15

    We have shown that the expression of several genes associated with human colon cancer is altered in the morphologically normal colonic mucosa (MNCM) of APC(min) mice and humans with colon cancers. To determine whether these alterations also occur in the MNCM of individuals who have not developed colon cancer but are at high risk of doing so, we measured gene expression in the MNCM of individuals with a family history of colon cancer. Expression of 16 genes in the MNCM of 12 individuals with a first-degree relative with sporadic colon cancer and 16 normal controls were measured by quantitative reverse transcription-PCR. All subjects tested had normal colonoscopic examinations. Biopsy samples of MNCM were obtained from the ascending, transverse, descending, and rectosigmoid regions of the colon (2-8 biopsy samples were obtained from each region). Relative to normal controls, the expression of several genes, including PPAR-gamma, SAA1, and IL-8 were significantly altered in the macroscopically normal rectosigmoid mucosa from individuals with a family history of colon cancer. Molecular abnormalities that precede the appearance of adenomatous polyp are present in the MNCM of individuals who have a family history of colon cancer. This observation raises the possibility of screening for individuals who are at an increased risk of developing colon cancer by analysis of gene expression in rectosigmoid biopsy samples. To assess this possibility, prospective studies will be needed to determine whether or not altered gene expression is associated with the subsequent development of adenomatous polyps and/ or colonic carcinomas.

  3. Synchronous lung tumours in a patient with metachronous colorectal carcinoma and a germline MSH2 mutation.

    LENUS (Irish Health Repository)

    Canney, A

    2012-02-01

    Mutations of DNA mismatch repair genes are characterised by microsatellite instability and are implicated in carcinogenesis. This mutation susceptible phenotype has been extensively studied in patients with hereditary non-polyposis colon carcinoma, but little is known of the contribution of such mutations in other tumour types, particularly non-small-cell lung carcinoma. This report describes the occurrence of two synchronous lung tumours, one mimicking a metastatic colon carcinoma, in a male patient with a history of metachronous colonic carcinoma. Immunohistochemistry supported a pulmonary origin for both lesions. Mismatch repair protein immunohistochemistry showed loss of MSH2 and MSH6 expression in both colonic tumours and in one lung tumour showing enteric differentiation. Subsequent mutational analysis demonstrated a deleterious germline mutation of the MSH2 mismatch repair gene. The significance of these findings and the practical diagnostic difficulties encountered in this case are discussed.

  4. Learning about Colon Cancer

    Science.gov (United States)

    ... Top of page Is there a test for hereditary colon cancer? Gene testing can identify individuals who carry the more ... looking for mutations in four of the five genes identified that are associated with ... Colon Cancer Currently, NHGRI is not conducting clinical research studies ...

  5. CT Findings of Colonic Complications Associated with Colon Cancer

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-04-15

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

  6. Understanding your colon cancer risk

    Science.gov (United States)

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

  7. [Complex characteristics of the alterations of oncogenes HER-2/ERBB-2, HER-1/ERBB-1, HRAS-1, C-MYC and antioncogenes p53, RB1, as well as deletions of loci of chromosome 17 in colon carcinoma].

    Science.gov (United States)

    Kniazev, P G; Imianitov, E N; Chernitsa, O I; Nikiforova, I F; Babenko, V I; Bruderliaĭn, S; Plutalo, O V; Kuz'min, A I; Kaboev, O K; Berlin, Iu A

    1992-01-01

    Abnormalities of some oncogenes, antioncogenes and losses of heterozygosity (LOH) of chromosome 11p, 17p, and 17q in colorectal carcinomas (CC) was studied. Amplification of ERBB-1/HER-1 oncogene was detected in 2 of 56 cases; ERBB-2/HER-2- in 4 of 62. There was a lack of evidence for C-MYC oncogene amplification (67 cases). LOH of chromosome 11p (HRAS-1 probe) was found in 2 of 37 informative (heterozygous) cases; such events were not accompanied by point mutations in "hot" codons (12th or 61st) in the remaining allele. Prevalence of A3 and A4 alleles of HRAS-1 oncogene (68 cases) as compared to healthy donors was noted. RB-1 (41 cases) and p53 (62 cases) suppressor genes did not show any alterations in Southern-blot analysis. LOH of chromosome 17p (YNZ-22 probe) was found in 15 of 26 heterozygous CC; 17q (THH-59 probe)--in 4 of 16. Analysis of 175th codon of p53 gene revealed only one case of mutation in 35 CC studied. Finally, we were able to detect genetic alterations in 23 of 40 (58%) CC, that were studied on each parameter using Southern-blot. We failed to find any correlation between various molecular abnormalities or clinical characteristics. The data obtained are in disagreement with the view concerning frequent involvement of p53 antioncogene in chromosome 17p deletions.

  8. TS Gene Polymorphisms Are Not Good Markers of Response to 5-FU Therapy in Stage III Colon Cancer Patients

    Directory of Open Access Journals (Sweden)

    A. Fariña-Sarasqueta

    2010-01-01

    Full Text Available Aim: Although the predictive and prognostic value of thymidylate synthase (TS expression and gene polymorphism in colon cancer has been widely studied, the results are inconclusive probably because of methodological differences. With this study, we aimed to elucidate the role of TS gene polymorphisms genotyping in therapy response in stage III colon carcinoma patients treated with 5-FU adjuvant chemotherapy.

  9. Fruits, vegetables, and hMLH1 protein-deficient and -proficient colon cancer: The Netherlands cohort study

    NARCIS (Netherlands)

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

    2005-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Murray B. Gordon

    2016-01-01

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

  11. Genetic alteration in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yoo Chul; Kang, Tae Woong; Lee, Jin Oh [Korea Cancer Center Hospital of Korea Atomic Energy Research Institute, Seoul (Korea, Republic of)

    1994-12-01

    Cancer of stomach, colon and liver are a group of the most common cancer in Korea. However, results with current therapeutic modalities are still unsatisfactory. The intensive efforts have been made to understand basic pathogenesis and to find better therapeutic tools for the treatment of this miserable disease. We studied the alteration of tumor suppressor genes and oncogenes in hepatocellular carcinoma in Korea. We found that alteration of Rb gene, APC were 33 %, 13 % respectively. But alterations of oncogenes such as myc, ras and mdm2 were rarely found. Our results suggests that HBV may act as oncogenic role in hepatocarcinogenesis instead of oncogenes. 6 figs, 2 tabs. (Author).

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

    Science.gov (United States)

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

    2015-01-01

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

  13. A possible new syndrome with growth-hormone secreting pituitary adenoma, colonic polyposis, lipomatosis, lentigines and renal carcinoma in association with familial testicular germ cell malignancy: A case report

    Directory of Open Access Journals (Sweden)

    Mai Phuong L

    2007-03-01

    Full Text Available Abstract Background Germ-cell testicular cancer has not been definitively linked to any known hereditary cancer susceptibility disorder. Familial testicular cancer in the presence of other findings in affected and unaffected family members might indicate a previously-unidentified hereditary cancer syndrome. Case presentation The patient was diagnosed with a left testicular seminoma at age 28, and treated with left orchiectomy followed by adjuvant cobalt radiation. His family history is significant for testicular seminoma in his son, bladder cancer in his sister, and lipomatosis in his father. His evaluation as part of an etiologic study of familial testicular cancer revealed multiple colon polyps (adenomatous, hyperplastic, and hamartomatous first found in his 50 s, multiple lipomas, multiple hyperpigmented skin lesions, left kidney cancer diagnosed at age 64, and a growth-hormone producing pituitary adenoma with associated acromegaly diagnosed at age 64. The patient underwent genetic testing for Cowden syndrome (PTEN gene, Carney complex (PRKAR1A gene, and multiple endocrine neoplasia syndrome type 1 (MEN1 gene; no deleterious mutations were identified. Discussion The constellation of benign and malignant neoplasms in the context of this patient's familial testicular cancer raised the possibility that these might be manifestations of a known hereditary susceptibility cancer syndrome; however, genetic testing for the three syndromes that were most likely to explain these findings did not show any mutation. Alternatively, this family's phenotype might represent a novel neoplasm susceptibility disorder. This possibility cannot be evaluated definitively on the basis of a single case report; additional observations and studies are necessary to investigate this hypothesis further.

  14. Death from colonic disease in epidermolysis bullosa dystrophica

    Directory of Open Access Journals (Sweden)

    Lin Gau-Tyan

    2006-02-01

    Full Text Available Abstract Background Squamous cell carcinomas and renal failure were reported the causes of death in patients with recessive dystrophic epidermolysis bullosa (RDEB. Death from colonic disease in epidermolysis bullosa (EB is never reported. Case presentation We demonstrate a male patient with RDEB. He suffered megacolon due to fecal impaction and died from sigmoid colon perforation with peritonitis at age 35 years. Conclusion Constipation is a common clinical feature of RDEB, but fetal complications of chronic constipation are rarely reported. To the author's best knowledge, it has not been reported or recognized in the English literature previously. The aggressive assessment of constipation with fecal impaction is recommended in patients with RDEB.

  15. Sonography in Colonic Diverticulitis

    Energy Technology Data Exchange (ETDEWEB)

    Sohn, Mi Yun; Choi, Byung Hun; Kim, Keum Won; Kwon, Kwi Ryun; Lim, Myung Ah; Kim, Sung Soo; Choi, Chang Ho [Sunlin Presbyterian Hospital, Pohang (Korea, Republic of)

    1996-06-15

    To evaluate the sonographic findings and the diagnostic value of colonic diverticulitis. We evaluated the sonograms of 26 patients with colonic diverticulitis retrospectively. The final diagnosis was based on the pathologic interpretation of a surgical specimen (5 cases), clinical course (21 cases), on barium enema (12 cases) and colonoscopy (1 case). Twenty-five patients had acute diverticulitis in the cecum and 1 patient in the descending colon. On sonography, an oval or short tubular focus which protruded from the colonic wall was seen in 23 patients (88%) and the longest diameter were from 0.5 cm to 3 cm (mean 1.4cm). The lesions were echogenic in 8 cases and hypoechoic in 17 cases. Segmental thickening of the colonic wall was seen in 13 patients (50%), of these, protruding focus was seen in 92%. Pericolic abscess located inposterolateral and medial portion to the colon was seen in 11 patients (42%). Infiltration in pericolic fat(50%), enlargement of pericolic lymph nodes (27%) and small pericolic fluid (8%) were also seen. Our results show that ultrasonography is useful technique in the diagnosis of colonic diverticulitis and in the differentiation from acute appendicitis

  16. Ameloblastic carcinoma

    Directory of Open Access Journals (Sweden)

    Praveen B Kumar

    2009-01-01

    Full Text Available Ameloblastoma of jaws are common and locally destructive tumors originating from odontogenic apparatus. They constitute approximately 1% of all jaw tumors with 80% occurring in the mandible. Ameloblastoma exhibiting a frank malignancy is a rare entity and occurs in less than 1% of all ameloblastomas. Among the two jaws, ameloblastic carcinoma involving maxilla is extremely rare with only few cases reported so far in the literature. Here we report two cases of ameloblastic carcinoma one involving the maxilla and the other involving mandible, with an aggressive clinical course leading to extensive local destruction of the affected jaws.

  17. An Act of Colonization

    DEFF Research Database (Denmark)

    Rasmussen, Anders Bo

    When Gideon Welles, U.S. Secretary of the Navy, sat down to write his diary entry on September 26, 1862, his thoughts turned once more to colonization. President Lincoln was an ardent proponent of colonization, “the government-promoted settlement of black Americans in Africa or some other locatio...... in the island of St. Croix,” and the Lincoln administration’s continued exploration of colonization arrangements in subsequent years, no further negotiations were carried out at that time and no laborers in American custody were shipped to St. Croix. This paper attempts to answer why....

  18. Colonic Disorders in Adult Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    Hugh Chaun

    2001-01-01

    Full Text Available By 1996, the median survival of patients with cystic fibrosis (CF in North America had increased to 31 years. With the markedly improved life expectancy, many CF patients are now adults. There is an associated increased risk of certain colonic disorders, and the emergence of other previously unrecognized disorders, in adult CF patients. The distal intestinal obstruction syndrome (DIOS, which is more common in older patients, is a frequent cause of abdominal pain. Intussusception may complicate DIOS; other differential diagnoses include appendiceal disease, volvolus, Crohn's disease, fibrosing colonopathy and colonic carcinoma. The diagnosis of acute appendicitis, although uncommon in patients with CF, is often delayed, and appendiceal abscess is a frequent complication. The prevalence of Crohn's disease in CF has been shown to be 17 times that of the general population. Right-sided microscopic colitis is a recently recognized entity in CF of uncertain clinical significance. Fibrosing colonopathy has been confined mostly to children with CF, attributed to the use of high strength pancreatic enzyme supplements, but it has been reported in three adults. Nine cases of carcinoma of the large intestine have been reported worldwide, associated with an apparent excess risk of digestive tract cancers in CF. Despite high carrier rates of Clostridium difficile in patients with CF, pseudomembranous colitis is distinctly rare, but severe cases complicated by toxic megacolon have been reported. In these patients, watery diarrhea is often absent. Adult CF patients with refractory or unexplained intestinal symptoms merit thorough investigations.

  19. NONO and RALY proteins are required for YB-1 oxaliplatin induced resistance in colon adenocarcinoma cell lines

    Directory of Open Access Journals (Sweden)

    Tsofack Serges P

    2011-11-01

    Full Text Available Abstract Background YB-1 is a multifunctional protein that affects transcription, splicing, and translation. Overexpression of YB-1 in breast cancers causes cisplatin resistance. Recent data have shown that YB-1 is also overexpress in colorectal cancer. In this study, we tested the hypothesis that YB-1 also confers oxaliplatin resistance in colorectal adenocarcinomas. Results We show for the first time that transfection of YB-1 cDNA confers oxaliplatin resistance in two colorectal cancer cell lines (SW480 and HT29 cell lines. Furthermore, we identified by mass spectrometry analyses important YB-1 interactors required for such oxaliplatin resistance in these colorectal cancer cell lines. A tagged YB-1 construct was used to identify proteins interacting directly to YB-1 in such cells. We then focused on proteins that are potentially involved in colorectal cancer progression based on the Oncomine microarray database. Genes encoding for these YB-1 interactors were also examined in the public NCBI comparative genomic hybridization database to determine whether these genes are localized to regions of chromosomes rearranged in colorectal cancer tissues. From these analyses, we obtained a list of proteins interacting with YB-1 and potentially involved in oxaliplatin resistance. Oxaliplatin dose response curves of SW480 and HT29 colorectal cancer cell lines transfected with several siRNAs corresponding to each of these YB-1 interactors were obtained to identify proteins significantly affecting oxaliplatin sensitivity upon gene silencing. Only the depletion of either NONO or RALY sensitized both colorectal cancer cell lines to oxaliplatin. Furthermore, depletion of NONO or RALY sensitized otherwise oxaliplatin resistant overexpressing YB-1 SW480 or HT29 cells. Conclusion These results suggest knocking down NONO or RALY significant counteracts oxaliplatin resistance in colorectal cancers overexpressing the YB-1 protein.

  20. Understanding Antegrade Colonic Enema (ACE) Surgery

    Science.gov (United States)

    ... Colonic Enema (ACE) Surgery Understanding Antegrade Colonic Enema (ACE) Surgery Antegrade colonic enema surgery (ACE) or Malone ... Print Full Article What is antegrade colonic enema (ACE) surgery? Antegrade colonic enema surgery (ACE) or Malone ...

  1. Carcinoma vulvar

    Directory of Open Access Journals (Sweden)

    Yamit Peñas Zayas

    2015-11-01

    Full Text Available El carcinoma de la vulva tiene una incidencia de aproximadamente un 3-5% dentro de todas las enfermedades ginecológicas malignas. El 90% de los tumores malignos de la vulva está constituido por carcinoma epidermoide, el resto son adenocarcinomas, carcinomas de células basales y melanomas. Se realiza la presentación de un caso de una paciente femenina de 25 años de edad con antecedentes  de Diabetes Mellitus tipo II y trombopatia, que ingresa en el servicio de ginecología con un cuadro cutáneo polimorfo, localizado en labios mayores y menores, dado por lesiones eritematoerosivas y vegetante, sospechándose clínicamente el diagnóstico  de un carcinoma epidermoide, corroborándose el mismo histológicamente al realizarse biopsia de piel. Se indicó tratamiento con quimioterapia. Por la edad de la paciente y ser menos frecuente en mucosa que en la piel,  motivo la presentación del caso.

  2. Parathyroid carcinoma

    DEFF Research Database (Denmark)

    Qvist, N; Krøll, L; Ladefoged, C

    1986-01-01

    Parathyroid carcinoma is a slow growing tumor, and the patients most often die from complications to the hypercalcemia. Therefore, any attempt should be made to remove local recurrence and metastasis surgically, as medical treatment is disappointing. A case treated with extensive vascular surgery...

  3. Nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Brennan Bernadette

    2006-06-01

    Full Text Available Abstract Nasopharyngeal carcinoma (NPC is a tumor arising from the epithelial cells that cover the surface and line the nasopharynx. The annual incidence of NPC in the UK is 0.3 per million at age 0–14 years, and 1 to 2 per million at age 15–19 years. Incidence is higher in the Chinese and Tunisian populations. Although rare, NPC accounts for about one third of childhood nasopharyngeal neoplasms. Three subtypes of NPC are recognized in the World Health Organization (WHO classification: 1 squamous cell carcinoma, typically found in the older adult population; 2 non-keratinizing carcinoma; 3 undifferentiated carcinoma. The tumor can extend within or out of the nasopharynx to the other lateral wall and/or posterosuperiorly to the base of the skull or the palate, nasal cavity or oropharynx. It then typically metastases to cervical lymph nodes. Cervical lymphadenopathy is the initial presentation in many patients, and the diagnosis of NPC is often made by lymph node biopsy. Symptoms related to the primary tumor include trismus, pain, otitis media, nasal regurgitation due to paresis of the soft palate, hearing loss and cranial nerve palsies. Larger growths may produce nasal obstruction or bleeding and a "nasal twang". Etiological factors include Epstein-Barr virus (EBV, genetic susceptibility and consumption of food with possible carcinogens – volatile nitrosamines. The recommended treatment schedule consists of three courses of neoadjuvant chemotherapy, irradiation, and adjuvant interferon (IFN-beta therapy.

  4. Laryngeal carcinoma

    African Journals Online (AJOL)

    Biological pharyngo-cutaneous fistula could not. One patient died markers of alcohol abuse in patients with from a ruptured carotid following radiotherapy three carcinoma of the larynx. Acta months after surgery, while the remaining eight are still. Otorrinolaringol Esp 1998 Aug- doing well with an average duration of follow ...

  5. Unusual metachronous isolated inguinal lymph node metastasis from adenocarcinoma of the sigmoid colon

    Directory of Open Access Journals (Sweden)

    Parodo Giuseppina

    2011-10-01

    Full Text Available Abstract This study aimed to describe an unusual case of metachronous isolated inguinal lymph nodes metastasis from sigmoid carcinoma. A 62-year-old man was referred to our department because of an obstructing sigmoid carcinoma. Colonoscopy showed the obstructing lesion at 30 cm from the anal verge and abdominal CT revealed a sigmoid lesion infiltrating the left lateral abdominal wall. The patient underwent a colonic resection extended to the abdominal wall. Histology showed an adenocarcinoma of the colon infiltrating the abdominal wall with iuxtacolic nodal involvement. Thirty three months after surgery abdominal CT and PET scan revealed a metastatic left inguinal lymph node involvement. The metastatic lymph node was found strictly adherent to the left iliac-femoral artery and encompassing the origin of the left inferior epigastric artery. Histology showed a metachronous nodal metastasis from colonic adenocarcinoma. Despite metastastic involvement of inguinal lymph node from rectal cancer is a rare but well known clinical entity, to the best of our knowledge, this is the first report of inguinal metastasis from a carcinoma of the left colon. Literature review shows only three other similar reported cases: two cases of inguinal metastasis secondary to adenocarcinoma of the cecum and one case of axillary metastasis from left colonic carcinoma. A metastatic pathway through superficial abdominal wall lymphatic vessels could be possible through the route along the left inferior epigastric artery. The solitary inguinal nodal involvement from rectal carcinoma could have a more favorable prognosis. In the case of nodal metastasis to the body surface lymph nodes from colonic carcinoma, following the small number of such cases reported in the literature, no definitive conclusions can be drawn.

  6. Immunohistochemistry in ocular carcinomas.

    Science.gov (United States)

    Sramek, Brett; Lisle, Allison; Loy, Timothy

    2008-07-01

    The distinction between ocular sebaceous carcinoma, poorly differentiated ocular squamous cell carcinoma and ocular basal cell carcinoma can be challenging. An appropriate immunohistochemical panel may help to differentiate these lesions. To determine the distribution and use of several immunostains in these specimens, formalin-fixed, paraffin-embedded tissue from several of each was studied using an immunohistochemical technique. Positive staining for cytokeratin (CK)7 was seen in 100% of sebaceous carcinomas, 77.8% of basal cell carcinomas and 67.7% of squamous cell carcinomas. One hundred percent of sebaceous and basal cell carcinomas were positive for cytokeratin CAM 5.2, while only 83.3% of squamous cell carcinomas were positive. Using epithelial membrane antigen (EMA), 100% of squamous cell carcinomas and 80% of sebaceous carcinomas were positive, while basal cell carcinomas were uniformly negative. One hundred percent of basal cell carcinomas and 80% of sebaceous carcinomas were positive for Ber-EP4, while all squamous cell carcinomas were negative. Finally, 77.8%, 20% and 16.7% of basal cell carcinomas, sebaceous carcinomas and squamous cell carcinomas showed immunoreactivity for the androgen receptor. An EMA positive, Ber-EP4 positive immunophenotype supports sebaceous carcinoma, EMA positive, Ber-EP4 negative result supports squamous cell carcinoma and an EMA negative, Ber-EP4 positive result supports basal cell carcinoma.

  7. Expression of p53, DCC, and HER-2/neu in Mucinous Carcinoma of the Breast

    OpenAIRE

    Hsu, Yung-Hsiang; Shaw, Cheng-Kuang

    2005-01-01

    We investigated the clinicopathologic and oncoprotein expression characteristics of 11 pure mucinous and 76 non-mucinous infiltrating ductal carcinomas in the human female breast. We compared patient age, tumor size, axillary lymph node status, and the expression of estrogen receptor (ER), progesterone receptor (PR), deleted-in-colon cancer (DCC), HER-2/neu, and p53. Mucinous carcinoma with axillary lymph node metastasis occurs less frequently than non-mucinous carcinoma (0% vs 63.1%; p = 0.0...

  8. Nodular liver lesions associated with chronic home hyperalimentation after massive enterectomy for ileal carcinoma.

    Science.gov (United States)

    Kemeny, M M

    1987-06-01

    A case of an ileal carcinoma involving the entire midgut treated with a massive enterectomy of the small bowel distal to the ligament of Treitz, the right colon, and part of the transverse colon is discussed. After 1 year on home hyperalimentation, hepatic nodules were seen on CT scans; metastases could not be proven. At 3 years a hepatic wedge resection was performed, multiple areas of necrosis and fibrosis were found, but no carcinoma. This case is presented as an example of an alternative in treatment for this type of carcinoma and to illustrate the problems of differential diagnosis of liver defects on the CT scan in patients on longterm hyperalimentation.

  9. Thyroid cancer - medullary carcinoma

    Science.gov (United States)

    Thyroid - medullary carcinoma; Cancer - thyroid (medullary carcinoma); MTC; Thyroid nodule - medullary ... The cause of medullary carcinoma of the thyroid (MTC) is unknown. ... and adults. Unlike other types of thyroid cancer, MTC is less ...

  10. Ameboma Mimicking Submucosal Tumor of the Colon in an Elderly

    Directory of Open Access Journals (Sweden)

    Shen-Yung Wang

    2011-06-01

    Full Text Available Ameboma is a rare presentation of intestinal amebiasis, which is caused by infection with Entamoeba histolytica. Amebomas are generally concentric and can be difficult to differentiate from carcinoma in the gastrointestinal tract, which are commonly seen in elderly patients. Radiological studies or colonoscopy can be difficult to provide the diagnosis. We present an elderly man with an ameboma in the ascending colon, which manifested as a submucosal tumor in the radiological or endoscopic studies. His serum antiamebic serology test was positive. He received surgery because of poor response to medical treatment. A full course of antiamebic therapy followed by a luminal agent were given and he had a smooth postoperative course without relapse of amebic infection. Although the elderly population has a higher incidence of colonic malignancy, ameboma should be considered in the differential diagnosis of submucosal tumors in the colon, especially in patients with an insidious onset of disease.

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

    Science.gov (United States)

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

    2015-09-01

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

  12. X-ray diagnosis in colorectal carcinoma as practised today - present state of the art

    Energy Technology Data Exchange (ETDEWEB)

    Beyer, D.

    1988-05-01

    Long-term prognosis of this malignant and frequent disease can be improved only by early diagnosis of small polyps and of carcinomas in the early stage. It is necessary to coordinate high-quality colon contrast medium enemas (double-contrast method) and hypotension with coloscopy and endoscopic removal of polyps. If a colon carcinoma is identified, it is additionally also necessary - probably mostly by colon enema - to exclude preoperatively a metachronic second carcinoma which can be expected in about 5% of the cases. Ultrasound and computed tomography will help in visualising advanced carcinomas that have already passed the wall and are borderline cases in respect of operability, as well as in identifying lymph node and liver metastases, besides in identifying complicating local perforations. Proof, however, is only rendered by a positive finding. It will be necessary to determine at what extent magnetic resonance can be useful in this context.

  13. Microcystic Variant of Urothelial Carcinoma

    Directory of Open Access Journals (Sweden)

    Anthony Kodzo-Grey Venyo

    2013-01-01

    Full Text Available Background. Microcystic variant of urothelial carcinoma is one of the new variants of urothelial carcinoma that was added to the WHO classification in 2004. Aims. To review the literature on microcystic variant of urothelial carcinoma. Methods. Various internet search engines were used to identify reported cases of the tumour. Results. Microscopic features of the tumour include: (i Conspicuous intracellular and intercellular lumina/microcysts encompassed by malignant urothelial or squamous cells. (ii The lumina are usually empty; may contain granular eosinophilic debris, mucin, or necrotic cells. (iii The cysts may be variable in size; round, or oval, up to 2 mm; lined by urothelium which are either flattened cells or low columnar cells however, they do not contain colonic epithelium or goblet cells; are infiltrative; invade the muscularis propria; mimic cystitis cystica and cystitis glandularis; occasionally exhibit neuroendocrine differentiation. (iv Elongated and irregular branching spaces are usually seen. About 17 cases of the tumour have been reported with only 2 patients who have survived. The tumour tends to be of high-grade and high-stage. There is no consensus opinion on the best option of treatment of the tumour. Conclusions. It would prove difficult at the moment to be dogmatic regarding its prognosis but it is a highly aggressive tumour. New cases of the tumour should be reported in order to document its biological behaviour.

  14. CT findings of colonic diverticulitis

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, Shigeru; Ohba, Satoru [Nagoya City Univ. (Japan). Medical School; Mizutani, Masaru [and others

    1998-11-01

    Although colonic diverticulitis has no indication for operation, but in some mistaken cases were operated with a diagnosis of acute appendicitis. We evaluated the CT findings of colonic diverticulitis about 19 cases and of asymptomatic colonic diverticula about 15 cases retrospectively. Diagnosis was confirmed of barium enema and operation. CT are complementary methods of examination that can delineated the range of thickening of the colon and the extension of inflammatory changes around the colon. We also believe that CT findings of colonic diverticulitis are useful for differentiating from a diagnosis of appendicitis. (author)

  15. Recent trend of colonic diverticulosis

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Yae Soon; Lee, Sung Woo; Han, Chang Yul; Lee, Kwan Seh [Inje Medical College, Seoul (Korea, Republic of)

    1988-08-15

    Colonic Diverticulosis is once thought to be a rare disease in Korea compared with western countries, but the incidence has been increasing with passage of time. Authors reviewed 151 cases of colon study with new double contrast method performed from November, 1986 to March, 1987 at Paik Hospital Inje college. The results were as follow: 1. The colonic diverticulosis was found in 39 cases out of 151 colon study (25.8%). 2. Colonic Diverticulosis were located at right and transvercolon in 54% and left and sigmoid colon in 18%. 3. Increasing occurrence in younger age group predilection; 4th decade was observed.

  16. EZH2 depletion blocks the proliferation of colon cancer cells.

    Directory of Open Access Journals (Sweden)

    Bettina Fussbroich

    Full Text Available The Enhancer of Zeste 2 (EZH2 protein has been reported to stimulate cell growth in some cancers and is therefore considered to represent an interesting new target for therapeutic intervention. Here, we investigated a possible role of EZH2 for the growth control of colon cancer cells. RNA interference (RNAi-mediated intracellular EZH2 depletion led to cell cycle arrest of colon carcinoma cells at the G1/S transition. This was associated with a reduction of cell numbers upon transient transfection of synthetic EZH2-targeting siRNAs and with inhibition of their colony formation capacity upon stable expression of vector-borne siRNAs. We furthermore tested whether EZH2 may repress the growth-inhibitory p27 gene, as reported for pancreatic cancer. However, expression analyses of colon cancer cell lines and colon cancer biopsies did not reveal a consistent correlation between EZH2 and p27 levels. Moreover, EZH2 depletion did not re-induce p27 expression in colon cancer cells, indicating that p27 repression by EZH2 may be cell- or tissue-specific. Whole genome transcriptome analyses identified cellular genes affected by EZH2 depletion in colon cancer cell lines. They included several cancer-associated genes linked to cellular proliferation or invasion, such as Dag1, MageD1, SDC1, Timp2, and Tob1. In conclusion, our results demonstrate that EZH2 depletion blocks the growth of colon cancer cells. These findings might provide benefits for the treatment of colon cancer.

  17. Transverse colon cancer occurring at a colostomy site 35 years after colostomy: a case report

    OpenAIRE

    Maeda, Chiyo; Hidaka, Eiji; Shimada, Mari; Shimada, Shoji; Nakahara, Kenta; Takayanagi, Daisuke; Takehara, Yusuke; Mukai, Shumpei; Sawada, Naruhiko; Ishida, Fumio; Kudo, Shin-Ei

    2015-01-01

    Background Carcinomas occurring at colostomy sites are rare, and most of these are metachronous colorectal cancers. The median time between colostomy and development of a carcinoma at a colostomy site is 22 years, which exceeds the length of the recommended follow-up period. We report a rare case of a carcinoma of the transverse colon occurring at a colostomy site in a patient without a history of colorectal cancer. Case report An 89-year-old woman presented with a tumor occurring at a colost...

  18. Carcinoma Basocelular

    Directory of Open Access Journals (Sweden)

    Inês Alencar de Castro

    2008-03-01

    Full Text Available Vemos na região frontal de um paciente masculino, fototipo II de Fitzpatrick, lesão ulcerada com bordas papulosas róseas e peroladas, correspondendo a Carcinoma Basocelular. É lesão maligna originária das células não- queratinizadas da camada basal da epiderme, sendo a forma mais comum de câncer em humanos. Estima-se em torno de 100.000 casos/ano no Brasil. Ocorre predominantemente em pele exposta de indivíduos com pouca capacidade de se bronzear. Pode se tornar invasivo, mas raramente metastatiza.

  19. Carcinoma basocelular

    OpenAIRE

    Nunes, Daniel Holthausen.

    2013-01-01

    Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde, Programa de Pós-Graduação em Ciências Médicas, Florianópolis, 2013. Introdução: O carcinoma basocelular (CBC) é o tumor maligno de pele mais comum em humanos. Atualmente existem inúmeras terapias para tratar o CBC, entretanto não se sabe se a inflamação peritumoral influencia na decisão cirúrgica, nem que fatores adicionais influenciam na qualidade de vida (QV) de seus portadores. Objetivos: 1) Aval...

  20. Excluding Lynch syndrome in a female patient with metachronous DNA mismatch repair deficient colon- and ovarian cancer.

    Science.gov (United States)

    Crobach, Stijn; Jansen, Anne M L; Ligtenberg, Marjolein J L; Koopmans, Marije; Nielsen, Maartje; Hes, Frederik J; Wijnen, Juul T; Dinjens, Winand N M; van Wezel, Tom; Morreau, Hans

    2017-11-09

    Patients synchronously or metachronously presenting with ovarian and colon cancer can pose diagnostic challenges. A primary colon carcinoma can metastasize to one or both ovaries, two independent primary tumors can arise or an ovarian carcinoma can metastasize to the colon. Clinical and immunohistochemical characterization can aid the diagnosis. Recently, we reported that in difficult cases finding pathogenic APC variants supports a colonic origin.In this case report we describe the clinical history of a female patient suspected for Lynch syndrome. She was diagnosed with a bilateral ovarian cancer at age 44, followed by the detection of a colon carcinoma 12.5 months later. Lesions of both sites showed a DNA mismatch repair deficiency with immunohistochemical loss of MLH1 and PMS2 expression without MLH1 promoter hypermethylation. In absence of germline MMR gene variants identical somatic MLH1 and CTNNB1 gene variants were found, indicating a clonal relation. MMR germline mosaicism was made unlikely by ultra deep sequencing of the MLH1 variant in DNA isolated from normal mucosa, blood, urine and saliva. Although initially being suspect for Lynch syndrome it was eventually concluded that a metachronously diagnosed colon carcinoma that metastasized to both ovaries was most likely.

  1. Unexpected Malignant Diagnosis in Colonic Biopsies: Malignant Transformation of Ovarian Mature Teratomas—Two Case Reports and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Claudia P. Rojas

    2015-01-01

    Full Text Available Colorectal adenocarcinoma is the second cause of cancer-related deaths in the United States. The occurrence of squamous cell carcinoma in the colorectum is extremely unusual. Malignant transformation from mature cystic teratoma of the ovary is a rare event. The most common transformation is squamous cell carcinoma, followed by adenocarcinoma. It occurs more often in elderly patients, who usually present with advance disease. We report two unusual cases of postmenopausal women diagnosed with squamous cell carcinoma in colon biopsies. After surgical resections, the carcinoma was proven to be the result of malignant transformation of ovarian mature cystic teratomas. Since squamous cell carcinoma of the colorectum is extremely rare, the presence of squamous cell carcinoma in a colonic biopsy in a female patient should alert the clinicians to other possible primary sites, as seen in these cases.

  2. Colonization, mouse-style

    Directory of Open Access Journals (Sweden)

    Searle Jeremy B

    2010-10-01

    Full Text Available Abstract Several recent papers, including one in BMC Evolutionary Biology, examine the colonization history of house mice. As well as background for the analysis of mouse adaptation, such studies offer a perspective on the history of movements of the humans that accidentally transported the mice. See research article: http://www.biomedcentral.com/1471-2148/10/325

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

    Science.gov (United States)

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

    2010-10-27

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

  4. External coating of colonic anastomoses

    DEFF Research Database (Denmark)

    Pommergaard, Hans-Christian; Achiam, Michael Patrick; Rosenberg, Jacob

    2012-01-01

    Colon anastomotic leakage remains both a frequent and serious complication in gastrointestinal surgery. External coating of colonic anastomoses has been proposed as a means to lower the rate of this complication. The aim of this review was to evaluate existing studies on external coating of colonic...

  5. P62/Ubiquitin IHC expression in gastrointestinal carcinomas

    Directory of Open Access Journals (Sweden)

    Amr eMohamed

    2015-03-01

    Full Text Available P62 and ubiquitin are small regulatory proteins demonstrated to have implications in the prognosis and survival of various malignancies including: hepatocellular, breast, ovarian, and some gastrointestinal carcinomas. Several trials studied the link of their activity to the extrinsic apoptosis pathway and showed that their autophagy modification has a critical stand point in tumorigenesis. These findings explain their vital role in controlling the process of cell death and survival. It has been shown recently that p62 and ubiquitin overexpression in different types of cancers, such as triple negative breast and ovarian cancers, have directly correlated with incidence of distant metastases. We aim to evaluate p62/ubiquitin expression in gastrointestinal carcinomas of gastric, colonic and pancreatic origin. In gastric carcinoma (45, positive p62 nuclear expression was noted in 53% and cytoplasmic in 57%, while positive ubiquitin was nuclear expressed in 80%, and cytoplasmic in 24%. In colon carcinoma (70, positive p62 nuclear expression was noted in 41% and cytoplasmic in 68.5%, while positive ubiquitin was nuclear in 57% and cytoplasmic in 42%. In pancreatic cancer, positive p62 nuclear expression was noted in 86% and cytoplasmic in 60%, while positive ubiquitin was nuclear in 100% and cytoplasmic in 80%. Normal gastric (6, colon (4 and pancreatic (4 tissues were negative for both P62 and ubiquitin (nuclear and cytoplasmic staining <20%. The results suggest that p62 and ubiquitin are highly expressed in nuclei and cytoplasm of gastric, colonic and pancreatic carcinomas. More studies are needed to correlate IHC expression of p62/ubiquitin with clinicopathologic parameters and overall survival in GI carcinomas.

  6. Role of colonic microbiota in colorectal carcinogenesis: a systematic review

    Directory of Open Access Journals (Sweden)

    Marta Borges-Canha

    2015-11-01

    Full Text Available Background and aim: The human colonic mucosa is populated by a wide range of microorganisms, usually in a symbiotic relation with the host. Sometimes this balance is lost and a state of dysbiosis arises, exposing the colon to different metabolic and inflammatory stimuli (according to the microbiota's changing profile. Recent findings lead to hypothesize that this unbalance may create a subclinical pro-inflammatory state that increases DNA mutations and, therefore, colorectal carcinogenesis. In this article we aim to systematically review the scientific evidence regarding colonic microbiota and its role in colorectal carcinogenesis. Methods: Systematic review of PubMed searching results for original articles studying microbiota and colorectal cancer until November 2014. Results: Thirty-one original articles studied the role of colon microbiota in colorectal carcinoma including both human and animal studies. Different and heterogeneous methods were used and different bacteria were considered. Nevertheless, some bacteria are consistently augmented (such as Fusobacteria, Alistipes, Porphyromonadaceae, Coriobacteridae, Staphylococcaceae, Akkermansia spp. and Methanobacteriales, while other are constantly diminished in colorectal cancer (such as Bifidobacterium, Lactobacillus, Ruminococcus, Faecalibacterium spp., Roseburia, and Treponema. Moreover, bacteria metabolites amino acids are increased and butyrate is decreased throughout colonic carcinogenesis. Conclusion: Conclusive evidence shows that colorectal carcinogenesis is associated with microbial dysbiosis. This information may be used to create new prophylactic, diagnostic and therapeutic strategies for colorectal cancer.

  7. Sacrum colon-rectal cancer metastasis: microwave ablation for palliative pain treatment.

    Science.gov (United States)

    Maiettini, Daniele; De Angelis, Verena; Graziosi, Luigina; Rebonato, Stefania; Falcinelli, Lorenzo; Metro, Giulio; Rebonato, Alberto

    2016-12-01

    Local treatment of bone metastasis (BM) remains controversial in colon-rectum carcinoma for pain control. A patient developed a sacrum BM 4years after a left colectomy for an adenocarcinoma. Metastasis was treated in one session of CT-guided microwave ablation showing good pain control immediately after and on follow-up at four months.

  8. Dietary mastic oil extracted from Pistacia lentiscus var. chia suppresses tumor growth in experimental colon cancer models.

    Science.gov (United States)

    Spyridopoulou, Katerina; Tiptiri-Kourpeti, Angeliki; Lampri, Evangeli; Fitsiou, Eleni; Vasileiadis, Stavros; Vamvakias, Manolis; Bardouki, Haido; Goussia, Anna; Malamou-Mitsi, Vasiliki; Panayiotidis, Mihalis I; Galanis, Alex; Pappa, Aglaia; Chlichlia, Katerina

    2017-06-19

    Plant-derived bioactive compounds attract considerable interest as potential chemopreventive anticancer agents. We analyzed the volatile dietary phytochemicals (terpenes) present in mastic oil extracted from the resin of Pistacia lentiscus var. chia and comparatively investigated their effects on colon carcinoma proliferation, a) in vitro against colon cancer cell lines and b) in vivo on tumor growth in mice following oral administration. Mastic oil inhibited - more effectively than its major constituents- proliferation of colon cancer cells in vitro, attenuated migration and downregulated transcriptional expression of survivin (BIRC5a). When administered orally, mastic oil inhibited the growth of colon carcinoma tumors in mice. A reduced expression of Ki-67 and survivin in tumor tissues accompanied the observed effects. Notably, only mastic oil -which is comprised of 67.7% α-pinene and 18.8% myrcene- induced a statistically significant anti-tumor effect in mice but not α-pinene, myrcene or a combination thereof. Thus, mastic oil, as a combination of terpenes, exerts growth inhibitory effects against colon carcinoma, suggesting a nutraceutical potential in the fight against colon cancer. To our knowledge, this is the first report showing that orally administered mastic oil induces tumor-suppressing effects against experimental colon cancer.

  9. Synchronous Occurrence of Primary Breast Carcinoma and Primary Colon Adenocarcinoma

    OpenAIRE

    Gurkan Yetkin; Fevzi Celayir; Ismail Ethem Akgun; Ramazan Ucak

    2017-01-01

    A 65-year-old female patient presented to the emergency clinic with abdominal pain, meteorism, and intermittent rectal bleeding. Colonoscopy was performed, and a hepatic flexure tumor was detected. Histopathological examination of biopsy revealed adenocarcinoma. Thoracoabdominal CT was performed for staging, and a spiculated contour mass was found incidentally on the left breast. Mammography and ultrasonography were performed for the cause of these findings, and suspicious lesions of malignan...

  10. Challenge in diagnosis and treatment of colonic carcinoma ...

    African Journals Online (AJOL)

    Alaa Hussein Abdel-Razek

    2012-01-23

    Jan 23, 2012 ... Abstract Introduction: Despite advances in perioperative care and operative techniques, urgent colorectal operations are still associated with higher mortality and morbidity than elective surgery. Aim: This study was to identify the challenge in diagnosis and treatment of emergencies caused by.

  11. Sonographic Features of Colonic Diverticulitis

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Yu Mee; Ko, Young Tae; Lim, Joo Won; Lee, Dong Ho; Yoon, Yup [Kyung Hee University Hospital, Seoul (Korea, Republic of)

    1996-06-15

    To evaluate sonographic features, location of diverticulum, and usefulness of sonography as a primary diagnostic tool. Sonographic findings of 28 patients with acute diverticulitis were reviewed. The diagnosis was made by surgery (11 patients), barium enema (20 patients), colonoscopy (3 patients), or CT (2 patients). There were 13 men and 15 women with ages ranging from 23 to 71 years old (mean, 33 years old). Sonographic abnormalities were seen in the cecum in 12 patients, both the cecum and ascending colon in seven, the ascending colon in six, the descending colon in two, and the transverse colon in one. On sonography, segmental thickening of the colonic wall was the most common finding, seen in 16 patients. The second most common finidngs were pericolic omental thickening and pericolic localized fluid collection (15 patients). Pericolic inflammatory mass of varying echogenicity (10 patients), out pouching hyper echoic foci beyond the lumen of the colon into or beyond the thickened wall (5 patients), contracture of the colon (5 patients), slightly thickened terminal ileum (1 patient), and local enlargement of ileocecal lymph node (1 patient) were also seen. Most diverticulitis occurred in the right colon. The useful sonographic findings in acute diverticulitis were echogenic foci of the diverticulum in the thickened colonic wall, focally and eccentrically thickened colonic wall, and localized omental thickening or fluid collection. In cases of pericecal fluid collection, appendicitis or colonic diverticulitis can be considered as a differential diagnosis

  12. Epidemiological, Clinico-Pathological Profile and Management of Colorectal Carcinoma in a Tertiary Referral Center of Eastern India

    OpenAIRE

    Shyamal Kumar Halder; Prosanta Kumar Bhattacharjee; Partha Bhar; Anadi Pachaury; Ranu Roy Biswas; Tapas Majhi; Pranjal Pandey

    2013-01-01

    Background: The colorectal carcinoma is a common cancer in males and in females and second most common cause of death in Europe and third commonest cause in the United States. Recent Indian study shows that there is a significant increase in incidence of colonic carcinoma but the incidence of rectal carcinoma remains steady. Aims and Objectives: This prospective study was undertaken to assess the clinico-pathological profile and management of colorectal malignanc...

  13. Ureteric carcinoma

    Directory of Open Access Journals (Sweden)

    Stephen A. Geller

    2014-03-01

    Full Text Available Ureteric neoplasms are rare tumors. The annual incidence (during the period 1995-2005 was 0,95-1,15/100.000 person-year. They are almost always urothelial tumors, especially papillary transitional cell carcinoma, as in the image above, and are less common than tumors of the renal pelvis and 10 times less common than urinary bladder tumors. In a large series of 1249 cases of urothelial neoplasms of the upper urinary tract (pelvis and ureter (upper urinary tract tumors; UUTT 34% of the cases involved the ureter, and in 8% the neoplasia was found in both sites concomitantly. Concomitance with bladder tumors is also observed, either synchronously or methachronously. When metachronous; bladder tumors precede UUTT in 10,2% of cases, and when synchronous in 49%.

  14. Parotid carcinoma

    DEFF Research Database (Denmark)

    Godballe, Christian; Schultz, Joyce H; Krogdahl, Annelise

    2003-01-01

    OBJECTIVE: To analyze clinical data and possible prognostic factors of patients with primary carcinoma of the parotid gland. STUDY DESIGN: A retrospective study was made of 85 patients with suspected parotid cancer who were admitted to the Center of Head and Neck Oncology at Odense University......%) were excluded from the analysis, leaving 75 individuals for the study. RESULTS: Twenty-four percent of patients were classified as T1, 32% as T2, 15% as T3, and 28% as T4. One patient (1%) was not classifiable (TX). Regional lymph node metastases were found in 17 cases (23%). Two of these were......-year recurrence-free survival of the entire study group was 63%, disease-specific survival was 69%, and crude survival was 52%. In univariate analysis, tumor size, histological appearance, T status, stage, the presence of lymph node metastases, distant metastases, pain, and facial nerve dysfunction had...

  15. On Justification of Colonization

    OpenAIRE

    Skov, Stig; Schrøder, Ulrikke; Mortensen, Marianne; Memic, Inda; Asmussen, Pernille

    2007-01-01

    Abstract The project concerns the justification of the Spanish colonization in America during the 16th and 17th century, examined through the Spanish philosopher Francisco de Vitoria’s (1485 – 1546) Political Writings and the British philosopher John Locke’s (1632- 1704) Two Treatises of Government, in a historical as well as a philosophical context. The main problem has been the dispossession of the Indians and how the philosophers defended the occupation of the lands of America. Vitoria’...

  16. Oesophageal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Cole, A. [Westmead Hospital, Westmead, NSW, (Australia). Department of Radiology

    1997-08-01

    Oesophageal carcinoma is an aggressive malignant tumour, and in Western countries accounts for only about 3 per cent of all malignancies. In other countries, such as China, this rate can be as high as 25 per cent, and as a result, is responsible for many deaths from malignancy. Despite this fairly low presentation rate in Westernised countries, the survival rate for sufferers beyond five years is dismal. This is also reflected in other parts of the world. Even with complex surgical techniques and Radiation Therapy, the survival rate has not improved markedly with these advanced techniques. This article gives a broad overview of Oesophageal Carcinoma, with a Westmead influence in reference to diagnosis, treatment and prognosis. The assessment of the tumour is done in a number of different ways. Barium Swallow is useful in assessing the length of the tumour. Endoscopy is also used to assess tumour length, this method being more sensitive than Barium Swallow. A CT of the Chest, Abdomen and Pelvis is performed to assess local spread, distant metastases and is also used for planning. The CT may be done as an Angio CT. Other methods of assessment used in a lesser extent, due to the technology being new, or from lack of experienced operators is MRI, endoscopic ultrasound and laparoscopic ultrasound. There are a number of different forms of treatment that may be considered, dependant upon the condition of the patient, and whether or not the tumour is considered `curable`. At Westmead Hospital, the considerations for treatment are: radiation therapy (as palliative therapy), surgery, combined radiation and chemotherapy and palliative therapy. 1 refs., 9 figs.

  17. Giant basal cell carcinoma Carcinoma basocelular gigante

    Directory of Open Access Journals (Sweden)

    Nilton Nasser

    2012-06-01

    Full Text Available The basal cell carcinoma is the most common skin cancer but the giant vegetating basal cell carcinoma reaches less than 0.5 % of all basal cell carcinoma types. The Giant BCC, defined as a lesion with more than 5 cm at its largest diameter, is a rare form of BCC and commonly occurs on the trunk. This patient, male, 42 years old presents a Giant Basal Cell Carcinoma which reaches 180 cm2 on the right shoulder and was negligent in looking for treatment. Surgical treatment was performed and no signs of dissemination or local recurrence have been detected after follow up of five years.O carcinoma basocelular é o tipo mais comum de câncer de pele, mas o carcinoma basocelular gigante vegetante não atinge 0,5% de todos os tipos de carcinomas basocelulares. O Carcinoma Basocelular Gigante, definido como lesão maior que 5 cm no maior diâmetro, é uma forma rara de carcinoma basocelular e comumente ocorre no tronco. Este paciente apresenta um Carcinoma Basocelular Gigante com 180cm² no ombro direito e foi negligente em procurar tratamento. Foi realizado tratamento cirúrgico e nenhum sinal de disseminação ou recorrência local foi detectada após 5 anos.

  18. Neoplasia de colon

    Directory of Open Access Journals (Sweden)

    Alina Torreblanca Xiques

    2014-12-01

    Full Text Available El cáncer de colon es un tumor que se desarrolla por degeneración maligna de las células del intestino grueso, desde la válvula ileocecal hasta la flexura recto sigmoidea. Se presenta el caso de un paciente masculino, de 75 años, con astenia anorexia y pérdida de peso; al examen físico: mucosas hipocoloreadas, abdomen blando no doloroso a la palpación superficial ni profunda. Se palpa aumento de volumen a nivel de la fosa ilíaca derecha, fija, de consistencia dura, ruidos hidroaereos normales. Se realizaron exámenes hematológicos, radiológicos y endoscópicos para el diagnóstico. Se tuvo la confirmación diagnóstica por anatomía patológica de adenocarcinoma de colon derecho, bien diferenciado. Se aplicó tratamiento primario, consistente en una amplia resección quirúrgica del cáncer del colon y el drenaje linfático regional, posteriormente se aplicó quimioterapia. El paciente evolucionó satisfactoriamente

  19. Colonic intussusception in descending colon: An unusual presentation of colon lipoma.

    Science.gov (United States)

    Bagherzadeh Saba, Reza; Sadeghi, Amir; Rad, Neda; Safari, Mohammad Taghi; Barzegar, Farnoush

    2016-12-01

    Lipomas of the colon are relatively rare benign soft tissue tumors derived from mature adipocytes of mesenchymatic origin. During colonoscopy, surgery or autopsy they are generally discovered incidentally. Most cases are asymptomatic, with a small tumor size, and do not need any special treatment. However, in the cases with larger in size of tumor some symptoms such as anemia, abdominal pain, constipation, diarrhea, bleeding, or intussusception may be presented. We reported a 47-year-old woman with colonic intussusception in the descending colon caused by colonic lipoma and diagnosed after surgical exploration for obstructive colonic mass.

  20. Effect of tea extracts, polyphenols, and epigallocatechin gallate on azoxymethane-induced colon cancer.

    Science.gov (United States)

    Weisburger, J H; Rivenson, A; Aliaga, C; Reinhardt, J; Kelloff, G J; Boone, C W; Steele, V E; Balentine, D A; Pittman, B; Zang, E

    1998-01-01

    Studies were conducted to determine the chemopreventive efficacy of several types of tea extracts on azoxymethane-induced colon cancer in male F344 rats. After determining the maximally tolerated dosage of the tea products, their effect in a colon cancer model was investigated. Groups of 36 male F344 rats received 2 subcutaneous doses of 15 mg/kg azoxymethane (AOM) at Weeks 6 and 7. Experimental groups also received as drinking fluids 3600 ppm of black or green tea extracts, 1800 ppm of EGCG, or 1800 ppm of black or green tea polyphenols beginning at 5 weeks of age. Additional groups drank a lower dose of 360 ppm of the five tea products. The experiments were terminated 43 weeks after the first tea exposure. No evidence of toxicity was observed since the body weight gain of all groups was similar. The rats given AOM had carcinoma of the small intestine and of the colon, classified histologically as in situ carcinoma, exophytic, invasive, and Peyer's patch carcinoma. In the small intestine, most of the neoplasms were classified as invasive, but in the colon, most were exophytic. The various tea products failed to produce a significant difference in the incidence of the several types of colon and small intestine carcinoma. The multiplicity of colon cancers ranged from 1.2-2.8 in all groups. The group on 3600 ppm of green tea had a significantly higher tumor multiplicity than the control group on AOM and water. Also, the group on 3600 ppm of green tea had a significantly higher tumor multiplicity than the group on 360 ppm. The tea products did not affect the development aspects of the tumors in most groups. The mechanisms underlying these findings rest on the fact that azoxymethane is metabolized mainly by cytochrome P450 2E1, and this enzyme system is not affected by tea.

  1. Rhabdoid Carcinoma of the Rectum

    Science.gov (United States)

    Samalavicius, Narimantas Evaldas; Gasilionis, Valdas; Baltruskeviciene, Edita; Aleknavicius, Eduardas; Mickys, Ugnius

    2013-01-01

    Rhabdoid colonic tumors are very rare lesions with just a few publications describing such neoplasms. Even more unusual for these lesions are their primary rectal locations, with only two brief case reports having been published on that subject to date. We present a case of a composite rhabdoid rectal carcinoma in a 49-year-old male. The tumor behaved very aggressively, with rapid patient demise despite radical surgery and intensive postoperative chemotherapy (FOLFIRI [folinic acid {leucovorin}, fluorouracil {5-fluorouracil}, and irinotecan] and FOLFOX4 [folinic acid {leucovorin}, fluorouraci {5-fluorouracil}, and oxaliplatin]). Pathologic examination was supportive of a rhabdoid carcinoma, with a compatible immunohistochemical profile, demonstrating synchronous expression of vimentin and epithelial markers in the tumor cells. In addition, BRAF V600E gene mutation, together with a wild-type KRAS gene, was identified, and no evidence of microsatellite instability based on MLH1, MSH2, MSH6, and PMS2 immunophenotypes, i.e., no loss of expression for all 4 markers, was observed. Our reported case confirms previously published observations of the clinical aggressiveness and the poor therapeutic response for rhabdoid tumors. PMID:24466541

  2. Liver cancer - hepatocellular carcinoma

    Science.gov (United States)

    Primary liver cell carcinoma; Tumor - liver; Cancer - liver; Hepatoma ... Hepatocellular carcinoma accounts for most liver cancers. This type of cancer occurs more often in men than women. It is usually diagnosed in people age 50 or ...

  3. Basal Cell Carcinoma

    Science.gov (United States)

    ... think Sebaceous carcinoma Skin cancer in people of color Skin reactions from targeted cancer therapy Squamous cell carcinoma What is Mohs surgery? Why see a board-certified dermatologist? Other conditions Diseases: A-Z index Skin, hair, and nail ...

  4. Squamous Cell Carcinoma

    Science.gov (United States)

    ... think Sebaceous carcinoma Skin cancer in people of color Skin reactions from targeted cancer therapy Squamous cell carcinoma What is Mohs surgery? Why see a board-certified dermatologist? Other conditions Diseases: A-Z index Skin, hair, and nail ...

  5. Abnormal distribution of collagen type IV in extrahepatic bile duct carcinoma.

    Science.gov (United States)

    Chen, Y; Sasatomi, E; Satoh, T; Miyazaki, K; Tokunaga, O

    2000-11-01

    The present study investigated the pathogenesis of desmoplastic stroma formation, which is characteristic of most bile duct carcinomas and other scirrhous carcinomas. Using immunohistochemical analysis, the expression of collagen types I and IV, laminin and TGF-beta1 was examined in human extrahepatic bile duct carcinoma and compared with gastric and colon carcinoma. In addition to delineating the basement membranes of carcinoma nests and blood vessels, collagen type IV was present along the thick bundles of collagenous fibers in the stroma of extrahepatic bile duct carcinoma and scirrhous gastric carcinoma. The immunoreactivity of collagen type IV was strong in the adjacent or surrounding interstitium of tumor cell nests, but was absent or weak in older, more central portions of the tumor that contained sclerotic collagen. In situ hybridization demonstrated active expression of collagen alpha1(IV) mRNA in extrahepatic bile duct carcinoma and scirrhous gastric carcinoma cells. These results suggest that, although collagen type IV is typically a component of the basement membrane, it is expressed in the interstitial stroma of extrahepatic bile duct carcinoma and scirrhous gastric carcinoma where it may play a role in desmoplastic stroma formation.

  6. [Liver metastases from colon and rectal cancer in terms of differences in their clinical parameters].

    Science.gov (United States)

    Liška, V; Emingr, M; Skála, M; Pálek, R; Troup, O; Novák, P; Vyčítal, O; Skalický, T; Třeška, V

    2016-02-01

    From the clinical point of view, rectal cancer and colon cancer are clearly different nosological units in their progress and treatment. The aim of this study was to analyse and clarify the differences between the behaviour of liver metastases from colon and rectal cancer. The study of these factors is important for determining an accurate prognosis and indication of the most effective surgical therapy and oncologic treatment of colon and rectal cancer as a systemic disease. 223 patients with metastatic disease of colorectal carcinoma operated at the Department of Surgery, University Hospital in Pilsen between January 1, 2006 and January 31, 2012 were included in our study. The group of patients comprised 145 men (65%) and 117 women (35%). 275 operations were performed. Resection was done in 177 patients and radiofrequency ablation (RFA) in the total of 98 cases. Our sample was divided into 3 categories according to the location of the primary tumor to C (colon), comprising 58 patients, S (c. sigmoideum) in 61 patients, and R (rectum), comprising 101 patients. Significance analysis of the studied factors (age, gender, staging [TNM classification], grading, presence of mucinous carcinoma, type of operation) was performed using ANOVA test. Overall survival (OS), disease-free interval (DFI) or no evidence of disease (NED) were estimated using Kaplan-Meier curves, which were compared with the log-rank and Wilcoxon tests. As regards the comparison of primary origin of colorectal metastases in liver regardless of their treatment (resection and RFA), our study indicated that rectal liver metastases showed a significantly earlier recurrence than colon liver metastases (shorter NED/DFI). Among other factors, a locally advanced finding, further R2 resection of liver metastases and positivity of lymph node metastases were statistically significant for the prognosis of an early recurrence of the primary colon and sigmoid tumor. Furthermore, we proved that in patients with

  7. Diverticulosis in total colonic aganglionosis

    Energy Technology Data Exchange (ETDEWEB)

    Ivancev, K.; Fork, T.; Haegerstrand, I.; Ivarsson, S.; Kullendorff, C.M.

    Two infants with total colonic aganglionosis (TCA) extending into the distal part of the ileum are described. Considerable diagnostic delay occurred with the correct diagnosis established first at 3 and 8 months, respectively. Radiologic findings compatible with TCA such as prolonged barium retention, reflux into ileum following barium enema, and foreshortening of colon were not clearly evident initially. Both patients demonstrated multiple acquired colon diverticula which increased both in number and size during the period of observation. These diverticula are probably a late manifestation of the spastic state of the anganglionic colon. Thus demonstration of diverticula supplies a strong evidence of TCA in infants with intestinal obstruction. (orig.).

  8. [Chromosomal rearrangements and fusion genes in carcinoma].

    Science.gov (United States)

    Massard, Christophe; Auger, Nathalie; Lacroix, Ludovic; Bénard, Jean

    2011-12-01

    In the last decades, rarity of chromosomal rearrangements and fusion genes detected in epithelial cancers in using classical karyotyping led to consider these genomic events as specifically restricted to haematological neoplasia and mesenchymal tumors. Today, gene positioning as well as bio-informatics approaches has enabled identifying in carcinoma various fusion genes subsequent to chromosomal translocations, inversions, or deletions. Thus, gene fusion formation appears as a common mechanism in oncology that concerns most of human cancers, independent of original tissue lineage. At a clinical point of view, applications of fusion genes in terms of diagnosis, prognosis and therapeutics can be envisioned. This review will present current knowledge about fusion genes in common carcinoma (prostate, breast, colon). Following a structural and functional description of various fusion genes so far found in human malignant solid tumors, as well as techniques used for their detection, the review will integrate fusion genes in epithelia oncogenesis general scheme. Finally, promising clinical issues of fusion genes will be surveyed.

  9. Novel roles of DC-SIGNR in colon cancer cell adhesion, migration, invasion, and liver metastasis.

    Science.gov (United States)

    Na, Heya; Liu, Xiaoli; Li, Xiaomeng; Zhang, Xinsheng; Wang, Yu; Wang, Zhaohui; Yuan, Menglang; Zhang, Yu; Ren, Shuangyi; Zuo, Yunfei

    2017-01-21

    Tumor metastasis is an essential cause of the poor prognosis of colon cancer. DC-SIGNR is a C-type lectin that is frequently found on human liver sinusoidal endothelial cells. LSECtin, which is a homologue of DC-SIGNR, has been demonstrated to participate in colon cancer liver metastasis. Due to the similarities in the expression pattern and structure of the two proteins, we speculated that DC-SIGNR could also be involved in this process. Colon cancer cells were treated with the DC-SIGNR protein or control IgG, after which cell migration, invasion, and morphology were assayed. Xenograft mouse models were used to determine the role of DC-SIGNR in colon cancer liver metastasis in vivo. In addition, a human gene expression array was used to detect differential gene expression in colon cancer cells stimulated with the DC-SIGNR protein. The serum level of DC-SIGNR was examined in colon cancer patients by ELISA, and the significance of DC-SIGNR was determined. In our research, we investigated whether DC-SIGNR promotes colon cancer cell adhesion, migration, and invasion. Knocking down mouse DC-SIGNR decreased the liver metastatic potency of colon cancer cells and increased survival time. Expressing human DC-SIGNR enhanced colon cancer liver metastasis. Furthermore, DC-SIGNR conferred metastatic capability on cancer cells by upregulating various metallothionein isoforms. To validate the above results, we also found that the serum DC-SIGNR level was statistically higher in colon cancer patients with liver metastasis compared with those without metastasis. These results imply that DC-SIGNR may promote colon carcinoma hepatic metastasis and could serve as a promising therapeutic target for anticancer treatment.

  10. Glycoprotein expression by adenomatous polyps of the colon

    Science.gov (United States)

    Roney, Celeste A.; Xie, Jianwu; Xu, Biying; Jabour, Paul; Griffiths, Gary; Summers, Ronald M.

    2008-03-01

    Colon cancer is the second leading cause of cancer related deaths in the United States. Specificity in diagnostic imaging for detecting colorectal adenomas, which have a propensity towards malignancy, is desired. Adenomatous polyp specimens of the colon were obtained from the mouse model of colorectal cancer called adenomatous polyposis coli-multiple intestinal neoplasia (APC Min). Histological evaluation, by the legume protein Ulex europaeus agglutinin I (UEA-1), determined expression of the glycoprotein α-L-fucose. FITC-labelled UEA-1 confirmed overexpression of the glycoprotein by the polyps on fluorescence microscopy in 17/17 cases, of which 13/17 included paraffin-fixed mouse polyp specimens. In addition, FITC-UEA-1 ex vivo multispectral optical imaging of 4/17 colonic specimens displayed over-expression of the glycoprotein by the polyps, as compared to non-neoplastic mucosa. Here, we report the surface expression of α-L-fucosyl terminal residues by neoplastic mucosal cells of APC specimens of the mouse. Glycoprotein expression was validated by the carbohydrate binding protein UEA-1. Future applications of this method are the development of agents used to diagnose cancers by biomedical imaging modalities, including computed tomographic colonography (CTC). UEA-1 targeting to colonic adenomas may provide a new avenue for the diagnosis of colorectal carcinoma by CT imaging.

  11. MALToma of the Transverse colon, Ascending colon and Caecum: A ...

    African Journals Online (AJOL)

    TNHJOURNALPH

    RESULT. We herein report a case of a 40-year-old male with mucosa - associated lymphoid tissue. [MALT] lymphoma of the transverse colon, ascending colon and caecum. He presented with severe abdominal pains and a centrally located huge abdominal mass for which a surgical resection was done. Histologically.

  12. DNA Topoisomerase I-Targeted Chemotherapy of Human Colon Cancer in Xenografts

    Science.gov (United States)

    Giovanella, Beppino C.; Stehlin, John S.; Wall, Monroe E.; Wani, Mansukh C.; Nicholas, Allan W.; Liu, Leroy F.; Silber, Robert; Potmesil, Milan

    1989-11-01

    Drug development is needed to improve chemotherapy of patients with locally advanced or metastatic colon carcinoma, who otherwise have an unfavorable prognosis. DNA topoisomerase I, a nuclear enzyme important for solving topological problems arising during DNA replication and for other cellular functions, has been identified as a principal target of a plant alkaloid 20 (S)-camptothecin. Significantly increased concentrations of this enzyme, compared to that in normal colonic mucosa, were found in advanced stages of human colon adenocarcinoma and in xenografts of colon cancer carried by immunodeficient mice. Several synthetic analogs of camptothecin, selected by tests with the purified enzyme and tissue-culture screens, were evaluated in the xenograft model. Unlike other anticancer drugs tested, 20(RS)-9-amino-camptothecin (9-AC) induced disease-free remissions. The overall drug toxicity was low and allowed for repeated courses of treatment.

  13. Anatomically correct deformable colon phantom

    Science.gov (United States)

    Norris, James A.; Barton, Michael D.; Davis, Brynmor J.; Bieszczad, Jerry; Meunier, Norm L.; Brown, Nathan W.; Kynor, David B.

    2011-03-01

    We describe a technique to build a soft-walled colon phantom that provides realistic lumen anatomy in computed tomography (CT) images. The technique begins with the geometry of a human colon measured during CT colonography (CTC). The three-dimensional air-filled colonic lumen is segmented and then replicated using stereolithography (SLA). The rigid SLA model includes large-scale features (e.g., haustral folds and tenia coli bands) down to small-scale features (e.g., a small pedunculated polyp). Since the rigid model represents the internal air-filled volume, a highly-pliable silicone polymer is painted onto the rigid model. This thin layer of silicone, when removed, becomes the colon wall. Small 3 mm diameter glass beads are affixed to the outer wall. These glass beads show up with high intensity in CT scans and provide a ground truth for evaluating performance of algorithms designed to register prone and supine CTC data sets. After curing, the silicone colon wall is peeled off the rigid model. The resulting colon phantom is filled with air and submerged in a water bath. CT images and intraluminal fly-through reconstructions from CTC scans of the colon phantom are compared against patient data to demonstrate the ability of the phantom to simulate a human colon.

  14. Colonic Diverticulitis in the Elderly

    Directory of Open Access Journals (Sweden)

    Chien-Kuo Liu

    2009-03-01

    Full Text Available Diverticular disease of the colon is a disease that mainly affects the elderly and presents in 50–70% of those aged 80 years or older. The most common complication is colonic diverticulitis. Eighty percent of patients who present with colonic diverticulitis are aged 50 years and older. Diagnosis and treatment of colonic diverticulitis in the elderly is more difficult and complicated owing to more comorbid conditions. Computed tomography is recommended for diagnosis when colonic diverticulitis is suspected. Most patients admitted with acute colonic diverticulitis respond to conservative treatment, but 15–30% of patients require surgery. Because surgery for acute colonic diverticulitis carries significant rates of morbidity and mortality, conservative treatment is recommended in the elderly. Conservative treatment of colonic diverticulitis with antibiotics, bowel rest, possibly including parenteral alimentation, is usually applied for 1–2 weeks. In the absence of a response to conservative treatment, frequent recurrence or complications (abscesses, fistulas, bowel obstructions, and free perforations, surgery is indicated.

  15. Transverse colon cancer occurring at a colostomy site 35 years after colostomy: a case report.

    Science.gov (United States)

    Maeda, Chiyo; Hidaka, Eiji; Shimada, Mari; Shimada, Shoji; Nakahara, Kenta; Takayanagi, Daisuke; Takehara, Yusuke; Mukai, Shumpei; Sawada, Naruhiko; Ishida, Fumio; Kudo, Shin-ei

    2015-05-06

    Carcinomas occurring at colostomy sites are rare, and most of these are metachronous colorectal cancers. The median time between colostomy and development of a carcinoma at a colostomy site is 22 years, which exceeds the length of the recommended follow-up period. We report a rare case of a carcinoma of the transverse colon occurring at a colostomy site in a patient without a history of colorectal cancer. An 89-year-old woman presented with a tumor occurring at a colostomy site. Thirty-five years previously, she had undergone a transverse loop colostomy for an iatrogenic colon perforation that occurred during left ureteral lithotomy. Upon physical examination, the patient had a hard nodule measuring 3 cm at the colostomy site. A biopsy of the nodule suggested adenocarcinoma, and the preoperative diagnosis was transverse colon cancer. A laparotomy was performed via a peristomal incision with 5-mm skin margins, and the tumor was covered by a surgical glove to avoid any tumor seeding. The colon was separated from the tumor by 5-cm margins, and the specimen was removed en bloc. An end colostomy was constructed to a new site on the right side of the abdomen. The deficit in the abdominal wall was repaired, and the skin was closed via a purse-string suture. The final diagnosis of the stoma tumor was transverse colon cancer (T2, N0, M0, stage I). One year and five months after surgery, there was no evidence of recurrence. The occurrence of carcinomas at colostomy sites in patients without a history of colorectal cancer is rare. It is important to train ostomates to monitor the stoma for possible tumor recurrence.

  16. Explant cultures of human colon

    DEFF Research Database (Denmark)

    Autrup, Herman; Barrett, L.A.; Jackson, F.E.

    1978-01-01

    . The ability to maintain colonic mucosa in culture was subject to both intra- and interindividual variation. Cultured human colonic mucosa also activated a chemical procarcinogen, benzo[a]pyrene, into metabolites which bound to cellular DNA. A 100-fold interindividual variation in this binding was observed.......Human colonic epithelium has been cultured as explants in a chemically defined medium for periods of 1 to 20 days. The viability of the explants was shown by the preservation of the ultrastructural features of the colonic epithelial cells and by active incorporation of radioactive precursors...... into cellular DNA and protein. A progressive decrease in the number of goblet cells, decrease in the depth of the crypts, and a change from a columnar to a cuboidal epithelium were observed. After 20 days in culture the colonic mucosa consisted of a single layer of cuboidal epithelial cells and a few glands...

  17. Enfermedad Diverticular del Colon

    OpenAIRE

    Gonzalo López Escobar

    1991-01-01

    Los divertículos del colon han sido reconocidos por varios observadores desde hace más de un siglo, pero en su mayor parte se trataba de casos aislados, hoy se la considera como la enfermedad del siglo XX, la de la era moderna y de los países industrializados y de avanzada tecnología (5,18,33).

    Según el diccionario de la Real Academia Española (11), divertículo, del latín, diverticulum, quiere decir desviación de un camino; y desde el punto de vista anatómico, apénd...

  18. Basal cell carcinoma of the skin with areas of squamous cell carcinoma: a basosquamous cell carcinoma?

    OpenAIRE

    de Faria, J

    1985-01-01

    The diagnosis of basosquamous cell carcinoma is controversial. A review of cases of basal cell carcinoma showed 23 cases that had conspicuous areas of squamous cell carcinoma. This was distinguished from squamous differentiation and keratotic basal cell carcinoma by a comparative study of 40 cases of compact lobular and 40 cases of keratotic basal cell carcinoma. Areas of intermediate tumour differentiation between basal cell and squamous cell carcinoma were found. Basal cell carcinomas with ...

  19. TNF Receptor-2 Facilitates an Immunosuppressive Microenvironment in the Liver to Promote the Colonization and Growth of Hepatic Metastases

    DEFF Research Database (Denmark)

    Ham, Boram; Wang, Ni; D'Costa, Zarina

    2015-01-01

    Successful colonization by a cancer cell of a distant metastatic site requires immune escape in the new microenvironment. TNF signaling has been implicated broadly in the suppression of immune surveillance that prevents colonization at the metastatic site and therefore must be blocked. In this st......Successful colonization by a cancer cell of a distant metastatic site requires immune escape in the new microenvironment. TNF signaling has been implicated broadly in the suppression of immune surveillance that prevents colonization at the metastatic site and therefore must be blocked....... In this study, we explored how TNF signaling influences the efficiency of liver metastasis by colon and lung carcinoma in mice that are genetically deficient for the TNF receptor TNFR2. We found a marked reduction in liver metastases that correlated with a greatly reduced accumulation at metastatic sites of CD...

  20. Colon tumor cells grown in NASA Bioreactor

    Science.gov (United States)

    2001-01-01

    These photos compare the results of colon carcinoma cells grown in a NASA Bioreactor flown on the STS-70 Space Shuttle in 1995 flight and ground control experiments. The cells grown in microgravity (left) have aggregated to form masses that are larger and more similar to tissue found in the body than the cells cultured on the ground (right). The principal investigator is Milburn Jessup of the University of Texas M. D. Anderson Cancer Center. The NASA Bioreactor provides a low turbulence culture environment which promotes the formation of large, three-dimensional cell clusters. Due to their high level of cellular organization and specialization, samples constructed in the bioreactor more closely resemble the original tumor or tissue found in the body. NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues being cultured in rotating bioreactors by investigators. Cell constructs grown in a rotating bioreactor on Earth (left) eventually become too large to stay suspended in the nutrient media. In the microgravity of orbit, the cells stay suspended. Rotation then is needed for gentle stirring to replenish the media around the cells. The work is sponsored by NASA's Office of Biological and Physical Research. The bioreactor is managed by the Biotechnology Cell Science Program at NASA's Johnson Space Center (JSC). Credit: NASA and University of Texas M. D. Anderson Cancer Center.

  1. Metastatic adenocarcinoma in a thyroid colloid nodule: a rare presentation of colon cancer.

    Science.gov (United States)

    Osin, P; Shiloni, E; Pikarsky, A J; Okon, E

    1996-08-01

    Colorectal cancer can remain asymptomatic for years. Frequently symptoms develop insidiously and may often remain unnoticed for long periods, even in the presence of disseminated disease. We herein report an unusual case of a patient with carcinoma of the sigmoid colon and multiple liver metastases. The diagnosis was established only after the patient was operated on for a large colloid nodule, a single microscopic metastatic focus being noticed in the histologic sections. The differential diagnosis compared with the columnar type of papillary carcinoma is discussed.

  2. Secondary effects induced by the colon carcinogen azoxymethane in BDIX rats

    DEFF Research Database (Denmark)

    Kobaek-Larsen, Morten; Fenger, Claus; Ritskes-Hoitinga, Jelmera

    2004-01-01

    Azoxymethane (AOM) is claimed to be a colon-specific carcinogen. In our studies, AOM was administered to adult BDIX/OrlIco rats by four weekly subcutaneous injections of 15 mg/kg body weight each - two periods of 2 weeks of AOM treatment separated by a one-week break. This treatment schedule...... resulted in colon carcinomas with a high frequency (75-100%) and with a high reproducibility. However, some serious side effects are associated with this carcinogen treatment. In addition to the colorectal tumours, we found small intestinal tumours, hepatic lesions and a high frequency of mesenchymal renal...

  3. [Anatomical study of pelvic colon].

    Science.gov (United States)

    James, Y E; Tchangai, B; Kassegne, I; Keke, K; James, K D

    2016-12-01

    Identifying the different kinds of anatomical sigmoid colon in our environment and determine what exposes the most to the occurrence of pelvic colon volvulus. This is a transverse prospective study from 1 January 2007 to 31 December 2012 on a series of 63 patients (33 men and 30 women) who underwent laparotomy for non-colonic pathologies. For all patients, the following parameters were recorded: C1: total length of the pelvic colon; C2: the length of the root of the meso-sigmoid; C3: the height of the meso-sigmoid; C4: maximum width of the meso-sigmoid. C1 through the entire series was 61,3cm. C2 average was 5.5cm. C3 height and maximum width C4 were on average 14,6cm and 7.6cm, respectively. Comparison of parameters in men and women showed no significant difference. This study allows us to know the different types of pelvic colons among the population of our operated patients. The measurements performed on the pelvic colon of patients presenting volvulus will help to attribute objectively the true authorship of this surgical emergency to an anatomical type of pelvic colon. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  4. Synchronous gastric neuroendocrine carcinoma and hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Ewertsen, Caroline; Henriksen, Birthe Merete; Hansen, Carsten Palnæs

    2009-01-01

    UNLABELLED: Gastric neuroendocrine carcinomas (NECs) are rare tumours that are divided into four subtypes depending on tumour characteristics. Patients with NECs are known to have an increased risk of synchronous and metachronous cancers mainly located in the gastrointestinal tract. A case...... of synchronous gastric NEC and hepatocellular carcinoma in a patient with several other precancerous lesions is presented. The patient had anaemia, and a gastric tumour and two duodenal polyps were identified on upper endoscopy. A CT scan of the abdomen revealed several lesions in the liver. The lesions were...... invisible on B-mode sonography and real-time sonography fused with CT was used to identify and biopsy one of the lesions. Histology showed hepatocellular carcinoma. A literature search showed that only one case of a hepatocellular carcinoma synchronous with a gastric NEC has been reported previously. TRIAL...

  5. Diverticulosis of colon: Case report

    Energy Technology Data Exchange (ETDEWEB)

    Han, Chang Yul [Paik Hospital, Seoul (Korea, Republic of)

    1972-12-15

    The authors reports 2 cases of diverticulosis involving the sacending colon and cecum: one, 55 year old, 85 kg Korean male admitted to Paik Hospital because of abdominal palm, constipation and tenderness in the right lower abdomen. The other, 48 year old, 78 kg male visited to our hospital for the routine examination. According to late European and American statistics, the colonic diverticulosis was discovered in late middle life about 20%, however, the incidence of colonic diverticulosis is rare in Korea. This paper presents a brief review of literature on the etiology, incidence and symptom.

  6. Vasohibin-1 suppresses colon cancer

    Science.gov (United States)

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

    2015-01-01

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

  7. Space Colonization: Problems and Prospects

    Directory of Open Access Journals (Sweden)

    Krichevskiy S. V.

    2012-04-01

    Full Text Available Space colonization is the top priority of mankind and the strategic target of manned cosmonautics. It is necessary to comprehend the outcome of human space flights and to give a new impulse to space expansion, scientific and practical solving the problem of space colonization by human beings. The attention is also paid to key issues, potentials, restrictions, forecasts, and prospects of space colonization as well as to the transformation of a man into "a man of the future", "homo cosmicus", and "a universal man", to the formation of "space mankind".

  8. Radiosensitization effects of sorafenib on colon cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Ho; Kim, Mi-Sook; Jung, Won-Gyun; Jeong, Youn Kyoung [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2014-11-15

    Radiotherapy is a standard therapy in the adjuvant treatment of resected colon and rectum cancers, and its combination with chemotherapy has been shown to reduce local failure and distant metastasis still further, thereby improving the outcome of treatment. One potential chemotherapeutic agent for this, sorafenib (Nexavar, BAY43-9006), is an oral multikinase inhibitor that blocks tumor cell proliferation and angiogenesis, and induces tumor cell apoptosis by inhibiting serine/threonine kinases (c-RAF and mutant and wild-type BRAF) as well as the receptor tyrosine kinases vascular endothelial growth factor receptor 2 and 3 (VEGFR2 and VEGFR3), platelet- derived growth factor receptor , FLT3, and c-KIT. Sorafenib is currently used in clinics to treat patients with advanced renal cell carcinoma, hepatocellular carcinoma, and thyroid cancer. These findings provide a molecular evidence base for the use of chemoradiation to treat colon cancer, and in vivo modeling should be used to further assess its suitability for clinical applications.

  9. Tumor budding in upper gastrointestinal carcinomas

    Directory of Open Access Journals (Sweden)

    Viktor Hendrik Koelzer

    2014-08-01

    Full Text Available The basis of personalized medicine in oncology is the prediction of an individual’s risk of relapse and death from disease. The presence of tumor budding (TB at the tumor-host interface of gastrointestinal cancers has been recognized as a hallmark of unfavorable disease biology. TB is defined as the presence of dedifferentiated cells or small clusters of up to five cells at the tumor invasive front and can be observed in aggressive carcinomas of the esophagus, stomach, pancreas, ampulla, colon and rectum. Presence of TB reproducibly correlates with advanced tumor stage, frequent lymphovascular invasion, nodal and distant metastasis. The UICC has officially recognized TB as additional independent prognostic factor in cancers of the colon and rectum. Recent studies have also characterized TB as a promising prognostic indicator for clinical management of esophageal squamous cell carcinoma, adenocarcinoma of the gastro-esophageal junction and gastric adenocarcinoma. However, several important issues have to be addressed for application in daily diagnostic practice: 1 Validation of prognostic scoring systems for tumor budding in large, multi-center studies 2 Consensus on the optimal assessment method 3 Inter-observer reproducibility. This review provides a comprehensive analysis of TB in cancers of the upper gastrointestinal tract including critical appraisal of perspectives for further study.

  10. Tumor Budding in Upper Gastrointestinal Carcinomas

    Science.gov (United States)

    Koelzer, Viktor H.; Langer, Rupert; Zlobec, Inti; Lugli, Alessandro

    2014-01-01

    The basis of personalized medicine in oncology is the prediction of an individual’s risk of relapse and death from disease. The presence of tumor budding (TB) at the tumor–host interface of gastrointestinal cancers has been recognized as a hallmark of unfavorable disease biology. TB is defined as the presence of dedifferentiated cells or small clusters of up to five cells at the tumor invasive front and can be observed in aggressive carcinomas of the esophagus, stomach, pancreas, ampulla, colon, and rectum. Presence of TB reproducibly correlates with advanced tumor stage, frequent lymphovascular invasion, nodal, and distant metastasis. The UICC has officially recognized TB as additional independent prognostic factor in cancers of the colon and rectum. Recent studies have also characterized TB as a promising prognostic indicator for clinical management of esophageal squamous cell carcinoma, adenocarcinoma of the gastro-esophageal junction, and gastric adenocarcinoma. However, several important issues have to be addressed for application in daily diagnostic practice: (1) validation of prognostic scoring systems for TB in large, multi-center studies, (2) consensus on the optimal assessment method, and (3) inter-observer reproducibility. This review provides a comprehensive analysis of TB in cancers of the upper gastrointestinal tract including critical appraisal of perspectives for further study. PMID:25177546

  11. 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....

  12. Post-Traumatic Right Lumbar Abscess as First Manifestation of Perforated Right Colon Cancer - A Case Report.

    Science.gov (United States)

    Rossetto, Anna; Cerato, Franz; Cedolini, Carla; Arena, Maria Concetta; Bresadola, Vittorio; Terrosu, Giovanni

    2010-02-23

    Besides most common signs and symptoms suggesting a colic cancer, sometimes the clinical presentation can be difficult. Extra-abdominal abscess as a first sign of perforated colon carcinoma is a very unusual finding. We report a case of an old male patient, in bad general condition, with a post-traumatic finding of right lumbar abscess. After the percutaneous drainage with discharge of fecal material and a postponed explorative laparotomy, we discovered a perforated right colon carcinoma with a covered perforation affecting the duodenum wall and spreading to the hepatic bedand over to the back lumbar muscular wall. Because of the diffusion of the tumor, the patient was treated with palliative surgery with duodenum suture, right colon segment resection and subsequent ileocolic anastomosis with an uneventful postoperative course. The patient died 2 months later because of neoplastic cachexia.

  13. Post-Traumatic Right Lumbar Abscess as First Manifestation of Perforated Right Colon Cancer – A Case Report

    Science.gov (United States)

    Rossetto, Anna; Cerato, Franz; Cedolini, Carla; Arena, Maria Concetta; Bresadola, Vittorio; Terrosu, Giovanni

    2010-01-01

    Besides most common signs and symptoms suggesting a colic cancer, sometimes the clinical presentation can be difficult. Extra-abdominal abscess as a first sign of perforated colon carcinoma is a very unusual finding. We report a case of an old male patient, in bad general condition, with a post-traumatic finding of right lumbar abscess. After the percutaneous drainage with discharge of fecal material and a postponed explorative laparotomy, we discovered a perforated right colon carcinoma with a covered perforation affecting the duodenum wall and spreading to the hepatic bedand over to the back lumbar muscular wall. Because of the diffusion of the tumor, the patient was treated with palliative surgery with duodenum suture, right colon segment resection and subsequent ileocolic anastomosis with an uneventful postoperative course. The patient died 2 months later because of neoplastic cachexia. PMID:20740157

  14. General Information about Colon Cancer

    Science.gov (United States)

    ... for information about colorectal cancer in children. Health history affects the risk of developing colon cancer. Anything ... and organs. This is called metastatic cancer. This animation shows how cancer cells travel from the place ...

  15. Vasohibin-1 suppresses colon cancer

    National Research Council Canada - National Science Library

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

    2015-01-01

    Vasohibin-1 (VASH1) is an endogenous angiogenesis inhibitor.However, the clinical relevance of VASH1 in colon cancer and its regulations on cancer angiogenesis and cancer cell biological characteristics are still unknown...

  16. Carcinoma basocelular gigante

    OpenAIRE

    Nilton Nasser; Nilton Nasser Filho; Bruno Trauczynski Neto; Lissandra Melati da Silva

    2012-01-01

    The basal cell carcinoma is the most common skin cancer but the giant vegetating basal cell carcinoma reaches less than 0.5 % of all basal cell carcinoma types. The Giant BCC, defined as a lesion with more than 5 cm at its largest diameter, is a rare form of BCC and commonly occurs on the trunk. This patient, male, 42 years old presents a Giant Basal Cell Carcinoma which reaches 180 cm2 on the right shoulder and was negligent in looking for treatment. Surgical treatment was performed and no s...

  17. Mucinous Carcinoma with Extensive Signet Ring Cell Differentiation: A Case Report

    Directory of Open Access Journals (Sweden)

    Hye Min Kim

    2017-03-01

    Full Text Available Breast cancers that present with mucin include mucinous carcinoma and carcinoma with signet ring cell differentiation. The former shows extracellular mucin and the latter shows abundant intracellular mucin. Here, we report a case of breast cancer showing both extracellular mucin and extensive signet ring cell differentiation due to abundant intracellular mucin. Unlike mucinous carcinoma, this case had the features of high-grade nuclear pleomorphism, high mitotic index, estrogen receptor negativity, progesterone receptor negativity, human epidermal growth factor receptor-2 positivity, and ductal type with positivity for E-cadherin. In a case with signet ring cell differentiation, differential diagnosis with metastatic signet ring cell carcinoma of the stomach and colon is essential. In this case, the presence of accompanied ductal carcinoma in situ component and mammaglobin and gross cystic disease fluid protein-15 positivity were findings that suggested the breast as the origin.

  18. Spontaneous Perforation of Rectosigmoid Colon

    Directory of Open Access Journals (Sweden)

    Farhad Haj Sheikholeslami

    2010-12-01

    Full Text Available Spontaneous perforation of the sigmoid colon or rectom is definedas a sudden perforation of the colon in the absence of diseasessuch as tumors, diverticulosis or external injury. It is avery rare finding, and if neglected, results in severe peritonitisand high mortality. The causes of this rare condition are numerous,and in this case it might be due to the chronic constipationinduced by an anticholinergic antipsychotic.Iran J Med Sci 2010; 35(4: 339-341.

  19. Colon in acute intestinal infection.

    Science.gov (United States)

    Guarino, Alfredo; Buccigrossi, Vittoria; Armellino, Carla

    2009-04-01

    The colon is actively implicated in intestinal infections not only as a target of enteric pathogens and their products but also as a target organ for treatment. In the presence of diarrhea, both of osmotic and secretory nature, the colon reacts with homeostatic mechanisms to increase ion absorption. These mechanisms can be effectively exploited to decrease fluid discharge. A model of intestinal infections using rotavirus (RV) in colonic cells was set up and used to define a dual model of secretory and osmotic diarrhea in sequence. Using this model, antidiarrheal drugs were tested, namely zinc and the enkephalinase inhibitor racecadotril. Zinc was able to decrease the enterotoxic activity responsible for secretory diarrhea. It also inhibited the cytotoxic effect of RV. The mechanism of zinc was related at least in part to the activation of MAPK activity, but also a direct antiviral effect was observed. Racecadotril showed a potent and selective inhibition of active secretion, being particularly effective in the first phase of RV diarrhea. The use of drugs active at the colonic level, therefore, offers effective options to treat intestinal infections in childhood. In addition, the colon is the natural site of colonic microflora, a target of probiotic therapy, which is the first line of approach recommended by the European Society for Paediatric Gastroenterology, Hepatology and Nutrition to treat infectious diarrhea.

  20. Atypical presentation of colon adenocarcinoma: a case report

    Directory of Open Access Journals (Sweden)

    Tumwine Lynnette K

    2012-02-01

    Full Text Available Abstract Introduction Adenocarcinoma of the colon is the most common histopathological type of colorectal cancer. In Western Europe and the United States, it is the third most common type and accounts for 98% of cancers of the large intestine. In Uganda, as elsewhere in Africa, the majority of patients are elderly (at least 60 years old. However, more recently, it has been observed that younger patients (less than 40 years of age are presenting with the disease. There is also an increase in its incidence and most patients present late, possibly because of the lack of a comprehensive national screening and preventive health-care program. We describe the clinicopathological features of colorectal carcinoma in the case of a young man in Kampala, Uganda. Case presentation A 27-year-old man from Kampala, Uganda, presented with gross abdominal distension, progressive loss of weight, and fever. He was initially screened for tuberculosis, hepatitis, and lymphoma, and human immunodeficiency virus/acquired immunodeficiency syndrome infection. After a battery of tests, a diagnosis of colorectal carcinoma was finally established with hematoxylin and eosin staining of a cell block made from the sediment of a liter of cytospun ascitic fluid, which showed atypical glands floating in abundant extracellular mucin, suggestive of adenocarcinoma. Ancillary tests with alcian blue/periodic acid Schiff and mucicarmine staining revealed that it was a mucinous adenocarcinoma. Immunohistochemistry showed strong positivity with CDX2, confirming that the origin of the tumor was the colon. Conclusions Colorectal carcinoma has been noted to occur with increasing frequency in young adults in Africa. Most patients have mucinous adenocarcinoma, present late, and have rapid disease progression and poor outcome. Therefore, colorectal malignancy should no longer be excluded from consideration only on the basis of a patient's age. A high index of suspicion is important in the

  1. Atypical presentation of colon adenocarcinoma: a case report.

    Science.gov (United States)

    Tumwine, Lynnette K; Kagimu, Magid; Ocama, Ponsiano; Segamwenge, Innocent; Masiira-Mukasa, Noah; Wamala, Dan; Dworak, Otto; Opio, Christopher K

    2012-02-13

    Adenocarcinoma of the colon is the most common histopathological type of colorectal cancer. In Western Europe and the United States, it is the third most common type and accounts for 98% of cancers of the large intestine. In Uganda, as elsewhere in Africa, the majority of patients are elderly (at least 60 years old). However, more recently, it has been observed that younger patients (less than 40 years of age) are presenting with the disease. There is also an increase in its incidence and most patients present late, possibly because of the lack of a comprehensive national screening and preventive health-care program. We describe the clinicopathological features of colorectal carcinoma in the case of a young man in Kampala, Uganda. A 27-year-old man from Kampala, Uganda, presented with gross abdominal distension, progressive loss of weight, and fever. He was initially screened for tuberculosis, hepatitis, and lymphoma, and human immunodeficiency virus/acquired immunodeficiency syndrome infection. After a battery of tests, a diagnosis of colorectal carcinoma was finally established with hematoxylin and eosin staining of a cell block made from the sediment of a liter of cytospun ascitic fluid, which showed atypical glands floating in abundant extracellular mucin, suggestive of adenocarcinoma. Ancillary tests with alcian blue/periodic acid Schiff and mucicarmine staining revealed that it was a mucinous adenocarcinoma. Immunohistochemistry showed strong positivity with CDX2, confirming that the origin of the tumor was the colon. Colorectal carcinoma has been noted to occur with increasing frequency in young adults in Africa. Most patients have mucinous adenocarcinoma, present late, and have rapid disease progression and poor outcome. Therefore, colorectal malignancy should no longer be excluded from consideration only on the basis of a patient's age. A high index of suspicion is important in the diagnosis of colorectal malignancy in young African patients.

  2. Normalization of the microbiota in patients after treatment for colonic lesions.

    Science.gov (United States)

    Sze, Marc A; Baxter, Nielson T; Ruffin, Mack T; Rogers, Mary A M; Schloss, Patrick D

    2017-11-16

    Colorectal cancer is a worldwide health problem. Despite growing evidence that members of the gut microbiota can drive tumorigenesis, little is known about what happens to it after treatment for an adenoma or carcinoma. This study tested the hypothesis that treatment for adenoma or carcinoma alters the abundance of bacterial populations associated with disease to those associated with a normal colon. We tested this hypothesis by sequencing the 16S rRNA genes in the feces of 67 individuals before and after treatment for adenoma (N = 22), advanced adenoma (N = 19), and carcinoma (N = 26). There were small changes to the bacterial community associated with adenoma or advanced adenoma and large changes associated with carcinoma. The communities from patients with carcinomas changed significantly more than those with adenoma following treatment (P value 0.05). Because the distribution of OTUs across patients and diagnosis groups was irregular, we used the random forest machine learning algorithm to identify groups of OTUs that could be used to classify pre and post-treatment samples for each of the diagnosis groups. Although the adenoma and carcinoma models could reliably differentiate between the pre- and post-treatment samples (P value 0.05). By better understanding the response of the microbiota to treatment for adenomas and carcinomas, it is likely that biomarkers will eventually be validated that can be used to quantify the risk of recurrence and the likelihood of survival. Although it was difficult to identify significant differences between pre- and post-treatment samples from patients with adenoma and advanced adenoma, this was not the case for carcinomas. Not only were there large changes in pre- versus post-treatment samples for those with carcinoma, but also these changes were toward a more normal microbiota.

  3. Fish oil ingestion reduces the number of aberrant crypt foci and adenoma in 1,2-dimethylhydrazine-induced colon cancer in rats.

    Science.gov (United States)

    Moreira, A P B; Sabarense, C M; Dias, C M G C; Lunz, W; Natali, A J; Glória, M B A; Peluzio, M C G

    2009-12-01

    We determined the effect of fish oil (FO) ingestion on colonic carcinogenesis in rats. Male Wistar rats received 4 subcutaneous injections (40 mg/kg body weight each) of 1,2-dimethylhydrazine (DMH) at 3-day intervals and were fed a diet containing 18% by weight FO (N = 10) or soybean oil (SO, N = 10) for 36 weeks. At sacrifice, the colon was removed, aberrant crypt foci were counted and the fatty acid profile was determined. Intestinal tumors were removed and classified as adenoma or carcinoma. Liver and feces were collected and analyzed for fatty acid profile. FO reduced the mean (+/- SEM) number of aberrant crypt foci compared to SO (113.55 +/- 6.97 vs 214.60 +/- 18.61; P colon was affected by diet (P 0.05). In conclusion, our findings indicate that chronic FO ingestion protected against the DMH-induced preneoplastic colon lesions and adenoma development, but not against carcinoma in rats.

  4. Peritoneal lymphomatosis confounded by prior history of colon cancer: a case report.

    Science.gov (United States)

    Kim, Yun Gi; Baek, Ji Yeon; Kim, Sun Young; Lee, Dong Hyeon; Park, Weon Seo; Kwon, Youngmee; Kim, Min Ju; Kang, Jeehoon; Lee, Joo Myung

    2011-06-27

    It is well known that carcinomas of the gastrointestinal tract are frequently associated with peritoneal carcinomatosis. In contrast to that entity extensive involvement of the peritoneal cavity with malignant lymphoma is rare. This is the first case reporting coexistence of peritoneal lymphomatosis and a previous history of colon cancer, which is a highly challenging clinical situation. If not aware of this unusual condition medical history, radiologic finding and laboratory data alone can lead to wrong diagnosis as in this case.

  5. Iberis amara Extract Induces Intracellular Formation of Reactive Oxygen Species and Inhibits Colon Cancer

    OpenAIRE

    Weidner, Christopher; Rousseau, Morten; Plauth, Annabell; Wowro, Sylvia J.; Fischer, Cornelius; Abdel-Aziz, Heba; Sauer, Sascha

    2016-01-01

    Massively increasing global incidences of colorectal cancer require efficient treatment and prevention strategies. Here, we report unexpected anticancerogenic effects of hydroethanolic Iberis amara extract (IAE), which is known as a widely used phytomedical product for treating gastrointestinal complaints. IAE significantly inhibited the proliferation of HT-29 and T84 colon carcinoma cells with an inhibitory concentration (IC50) of 6 and 9 μg/ml, respectively, and further generated inhibitory...

  6. Vulvar Villoglandular Adenocarcinoma of Colonic Type: A Rare Finding

    Directory of Open Access Journals (Sweden)

    Heidarali Esmaeili

    2018-01-01

    Full Text Available Colonic type villoglandular adenocarcinoma of the lower genital tract is an extremely rare condition. Its origin is not clearly understood; however, the cloacal remnants are the more accepted source for this carcinoma.We report the case of a 67-year-old female patient who presented with a 1.2 cm polypoidal nodule at the right side of the fourchette. Morphologic studies revealed a colonic type mucinous adenocarcinoma that arose from within a villous adenoma. Immunohistochemical staining showed positive cytokeratin 7, cytokeratin 20, carcinoembryonic antigen, P53, and progesterone receptor, but negative for estrogen receptor and caudal type homeobox transcription factor 2. Extensive work-up failed to reveal other primary cancers in this patient. Ultimately, she underwent a radical vulvectomy. No recurrence was seen in eight months follow up of this patient after surgery. Careful, thorough histological evaluation and clinical clues enable correct diagnosis of the rare colonic type vulvar villoglandular adenocarcinoma. Due to rarity of this tumor, its management is questionable. Therefore, additional investigation is necessary for its management.

  7. Prognostic significance of COX-2 and β-catenin in colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Amani Kazem

    2014-09-01

    Conclusion: Both β-catenin and COX-2 expression may play an important role in the evolution of colon carcinogenesis. Increased expression of both could be used as a marker of tumor progression and poor prognosis. This might be of therapeutic value for allocating patients with colorectal carcinoma to different treatment modalities.

  8. Regulatory role of zinc on the biokinetics and biodistribution of (65)Zn during the initiation of experimentally induced colon cancer.

    Science.gov (United States)

    Chadha, Vijayta Dani; Goel, Ajay; Dhawan, D

    2011-01-01

    The present study was conducted to evaluate the kinetics of zinc utilization during the formation of colon carcinoma in an animal model of colon carcinogenesis. The rats were segregated into 4 groups: untreated control, 1,2-dimethylhydrazine (DMH) treated, zinc treated, and DMH+zinc treated. Colon carcinogenesis was initiated through weekly subcutaneous injections of DMH (30 mg/kg body weight) for 8 wk. Zinc (in the form of zinc sulphate) was supplemented at a dose level of 227 mg/L in drinking water, ad libitum for the entire duration of study. Whole body (65)Zn kinetics followed two-compartment kinetics, with Tb(1) representing the initial fast component of the biological half-life and Tb(2), the slower component. The Tb(1) component showed a significant elevation while the Tb(2) component was significantly diminished in DMH-treated rats, which, however, got normalized following zinc supplementation. The biodistribution and subcellular distribution of (65)Zn was significantly affected in DMH-treated rats when compared to normal control rats. However, zinc significantly reversed the altered (65)Zn uptake in different organs and various fractions of colon. The present study for the first time demonstrated a faster mobilization of zinc during initiation of experimentally induced colon carcinoma and provides a physiological basis for the role of zinc in colon tumorigenesis. Copyright © 2011, Taylor & Francis Group, LLC

  9. An Unusual Clinical Presentation of Gastrointestinal Metastasis From Invasive Lobular Carcinoma of Breast.

    Science.gov (United States)

    Balakrishnan, Bathmapriya; Shaik, Sufiya; Burman-Solovyeva, Irina

    2016-01-01

    Introduction. We present an unusual case of metastatic lobular breast carcinoma. Typical areas of metastasis include bone, gynecological organs, peritoneum, retroperitoneum, and gastrointestinal (GI) tract, in order of frequency. With regard to GI metastasis, extrahepatic represents a rare site. Case. Two years after being diagnosed with invasive lobular breast carcinoma, a 61-year-old female complained of 3 months of nonspecific abdominal pain and diarrhea. A colonoscopy revealed 5 tubular adenomatous polyps in the ascending and transverse colon. Contrast computed tomography (CT) of the abdomen and pelvis was done 7 months after the colonoscopy to further evaluate persistent diarrhea. The CT results were consistent with infectious or inflammatory enterocolitis. Despite conservative management, symptoms failed to improve and a repeat diagnostic colonoscopy was obtained. Random colonic biopsies revealed metastatic high-grade adenocarcinoma of the colon. Discussion. Metastatic lobular breast carcinoma to the GI tract can distort initial interpretation of endoscopic evaluation with lesions mimicking inflammation. The interval between discovery of GI metastasis and diagnosis of lobular breast cancer can vary widely from synchronous to 30 years; however, progression is most often much sooner. Nonspecific symptoms and subtle appearance of metastatic lesions may confound the diagnosis. A high index of suspicion is needed for possible metastatic spread to the GI tract in patients with a history of invasive lobular breast carcinoma. Perhaps, patients with nonspecific GI symptoms should have an endoscopic examination with multiple random biopsies as invasive lobular carcinoma typically mimics macroscopic changes consistent with colitis.

  10. An Unusual Clinical Presentation of Gastrointestinal Metastasis From Invasive Lobular Carcinoma of Breast

    Directory of Open Access Journals (Sweden)

    Bathmapriya Balakrishnan MD

    2016-03-01

    Full Text Available Introduction. We present an unusual case of metastatic lobular breast carcinoma. Typical areas of metastasis include bone, gynecological organs, peritoneum, retroperitoneum, and gastrointestinal (GI tract, in order of frequency. With regard to GI metastasis, extrahepatic represents a rare site. Case. Two years after being diagnosed with invasive lobular breast carcinoma, a 61-year-old female complained of 3 months of nonspecific abdominal pain and diarrhea. A colonoscopy revealed 5 tubular adenomatous polyps in the ascending and transverse colon. Contrast computed tomography (CT of the abdomen and pelvis was done 7 months after the colonoscopy to further evaluate persistent diarrhea. The CT results were consistent with infectious or inflammatory enterocolitis. Despite conservative management, symptoms failed to improve and a repeat diagnostic colonoscopy was obtained. Random colonic biopsies revealed metastatic high-grade adenocarcinoma of the colon. Discussion. Metastatic lobular breast carcinoma to the GI tract can distort initial interpretation of endoscopic evaluation with lesions mimicking inflammation. The interval between discovery of GI metastasis and diagnosis of lobular breast cancer can vary widely from synchronous to 30 years; however, progression is most often much sooner. Nonspecific symptoms and subtle appearance of metastatic lesions may confound the diagnosis. A high index of suspicion is needed for possible metastatic spread to the GI tract in patients with a history of invasive lobular breast carcinoma. Perhaps, patients with nonspecific GI symptoms should have an endoscopic examination with multiple random biopsies as invasive lobular carcinoma typically mimics macroscopic changes consistent with colitis.

  11. HRAS1 minisatellite alleles in colorectal carcinoma: relationship to microsatelite instability.

    Science.gov (United States)

    Vega, A; Barros, F; Lleonart, M E; Ramon y Cajal, S; Carracedo, A

    2001-01-01

    To further evaluate sporadic colon carcinoma risk associated with rare HRAS1 VNTR alleles, the relationship with microsatellite instability and with HRAS1 VNTR instability. The HRAS1 VNTR was genotyped in 121 tumors and normal samples from sporadic colon carcinoma patients (47 right and 74 left colon) and in 109 samples from healthy individuals. The HRAS1 alleles were identified using PCR and automatic fluorescent electrophoresis detection combined with MVR-PCR (Minisatellite Variant Repeat-Polymerase Chain Reaction). Microsatellite Instability (MI) was analysed with 10 microsatellite markers. A relative risk of 3.04 (95% CI: 1.16-4.92) associated with rare alleles was obtained. No HRAS1 minisatellite instability was present in the tumors. Samples with MI were equally distributed between the common and rare HRAS1 allele groups, while the distribution of HRAS1 alleles in samples with MI was similar in right and left colorectal carcinoma. Rare HRAS1 VNTR alleles are associated with colorectal carcinoma risk independent of the tumor location. MI is not likely to be involved in the same underlying defect that generates rare HRAS1 alleles in colorectal carcinoma.

  12. Salivary gland carcinomas

    DEFF Research Database (Denmark)

    Therkildsen, M H; Andersen, L J; Christensen, M

    1998-01-01

    The prognosis of salivary gland carcinomas is difficult to assess. Simple mucin-type carbohydrates (T and sialosyl-T antigens, Tn and sialosyl-Tn antigens) have been shown to be of value in predicting prognosis for carcinomas in other locations. We studied the prognostic significance...

  13. [Case of Colon Metastasis from Early Gastric Cancer 4 Years after Laparoscopic Assisted Distal Gastrectomy].

    Science.gov (United States)

    Ikeda, Kosuke; Sato, Tsutomu; Maezawa, Yukio; Kano, Kazuki; Satoyoshi, Tetsuta; Segami, Kenki; Nakajima, Tetsushi; Ogata, Takashi; Cho, Haruhiko; Yoshikawa, Takaki

    2016-11-01

    A 69-year-old woman who underwent laparoscopic assisted distal gastrectomy for early gastric cancer(pathological T1bN1M0)in June 2011was admitted to the hospital because of abdominal pain in May 2015.A n abdominal CT scan showed ileus caused by a transverse colon tumor and ascending colon perforation.We performed emergency right hemicolectomy and diverting ileostomy.The postoperative pathological findings revealed poorly differentiated adenocarcinoma and signetring cell carcinoma similar to the gastric cancer resected 4 years ago.Immunohistochemical findings showed that the colon tumor was positive for CK7, but negative for CK20 and expressed a gastric mucin phenotype.From these findings, the colon tumor was diagnosed as a metastasis from early gastric cancer.Colon metastasis from early gastric cancer is rare and the diagnosis is difficult in some cases.We herein report this case and discuss the clinical and pathologic features of colon metastasis from gastric cancer.

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

    Science.gov (United States)

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

    2017-01-15

    Multistep model of colon carcinogenesis has provided the framework to advance our understanding of the molecular basis of colon cancer. This multistage process of carcinogenesis takes a long period to transform from a normal epithelial cell to invasive carcinoma. Thus, it provides enough time to intervene the process of carcinogenesis especially through dietary modification. In spite of the in-depth understanding of the colon cancer etiology and pathophysiology and its association with diet, colon cancer remains a major cause of cancer mortality worldwide. Phytochemicals and their derivatives are gaining attention in cancer prevention and treatment strategies because of cancer chemotherapy associated adverse effects. Being the largest group of phytochemicals traditionally used for medicinal purpose in India and China, terpenoids are recently being explored as anticancer agents. Anticancer properties of terpenoids are associated with various mechanisms like counteraction of oxidative stress, potentiating endogenous antioxidants, improving detoxification potential, disrupting cell survival pathways and inducing apoptosis. This review gives a comprehensive idea of naturally occurring terpenoids as useful agents for the prevention of colon cancer with reference to their classes, sources and molecular targets. Based on the explored molecular targets further research in colon cancer chemoprevention is warranted. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Deficiency in the 15 kDa Selenoprotein Inhibits Human Colon Cancer Cell Growth

    Directory of Open Access Journals (Sweden)

    Ryuta Tobe

    2011-09-01

    Full Text Available Selenium is an essential micronutrient for humans and animals, and is thought to provide protection against some forms of cancer. These protective effects appear to be mediated, at least in part, through selenium-containing proteins (selenoproteins. Recent studies in a mouse colon cancer cell line have shown that the 15 kDa selenoprotein (Sep15 may also play a role in promoting colon cancer. The current study investigated whether the effects of reversing the cancer phenotype observed when Sep15 was removed in mouse colon cancer cells, were recapitulated in HCT116 and HT29 human colorectal carcinoma cells. Targeted down-regulation of Sep15 using RNAi technology in these human colon cancer cell lines resulted in similarly decreased growth under anchorage-dependent and anchorage-independent conditions. However, the magnitude of reduction in cell growth was much less than in the mouse colon cancer cell line investigated previously. Furthermore, changes in cell cycle distribution were observed, indicating a delayed release of Sep15 deficient cells from the G0/G1 phase after synchronization. The potential mechanism by which human colon cancer cells lacking Sep15 revert their cancer phenotype will need to be explored further.

  16. Primary cutaneous myoepithelial carcinoma

    DEFF Research Database (Denmark)

    Frost, Markus Winther; Steiniche, Torben; Damsgaard, Tine Engberg

    2013-01-01

    This study describes a case of primary myoepithelial carcinoma of the skin and reviews the available literature on this topic. Myoepitheliomas and carcinomas arise most frequently from myoepithelial cells within the salivary glands but are found in many anatomical locations. We documented a case...... of an 80-year-old man with a 2 × 2 × 1 cm tumour located on the scalp. This tumour emerged over a period of 2 months. The tumour was radically excised, and histological examination revealed a cutaneous myoepithelial carcinoma. At an 18-month follow-up, no recurrence of the tumour was found. A systematic...... literature search identified 23 papers that reported 58 cases of cutaneous myoepitheliomas and myoepithelial carcinomas. All cases are reviewed in the presented paper. This case report and literature review serves to increase awareness regarding myoepithelial carcinomas. These tumours exhibit high metastatic...

  17. Mammary Analogue Secretory Carcinoma.

    Science.gov (United States)

    Stevens, Todd M; Parekh, Vishwas

    2016-09-01

    Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumor that shares the same histologic appearance and ETV6 gene (12p13) rearrangement as secretory carcinoma of the breast. Prior to its recognition, MASC cases were commonly labeled acinic cell carcinoma and adenocarcinoma, not otherwise specified. Despite distinctive histologic features, MASC may be difficult to distinguish from other salivary gland tumors, in particular zymogen-poor acinic cell carcinoma and low-grade salivary duct carcinoma. Although characteristic morphologic and immunohistochemical features form the basis of a diagnosis of MASC, the presence of an ETV6-NTRK3 gene fusion is confirmatory. Given its recent recognition the true prognostic import of MASC is not yet clearly defined.

  18. Enfermedad Diverticular del Colon

    Directory of Open Access Journals (Sweden)

    Gonzalo López Escobar

    1991-06-01

    Full Text Available

    Los divertículos del colon han sido reconocidos por varios observadores desde hace más de un siglo, pero en su mayor parte se trataba de casos aislados, hoy se la considera como la enfermedad del siglo XX, la de la era moderna y de los países industrializados y de avanzada tecnología (5,18,33.

    Según el diccionario de la Real Academia Española (11, divertículo, del latín, diverticulum, quiere decir desviación de un camino; y desde el punto de vista anatómico, apéndice hueco y terminado en fondo de saco. (Gráfica No. 1.

    Goligher (17 lo define como la “posada al borde del camino, probablemente un lugar, a menudo, de mala reputación”.

    Historia

    Según Hackford (18, el proceso fué descrito brevemente por Littre a comienzos del siglo XVIII; pero se le atribuye a Cruveilhier la primera descripción como proceso patológico en 1849, quien, además, mencionó: “encontramos, no rara vez, en el sigmoide, entre las bandas de fibras musculares longitudinales, una serie de pequeños tumores piriformes oscuros, que están formados por hernias de la mucosa a través de brechas en la capa muscular” (17.

    Fleischman en 1815 hizo la primera observación de la enfermedad y empleó el término divertículo (45.

    Rokitansky en 1.849, habló de una enfermedad adquirida y consideró que su causa consistía en la constipación (45.

    Virchowen 1853 describió la perisigmoiditis (45.

    En 1859 Sidney Jones informó de una fístula colo-vesical debida a diverticulitis (5,45.

    Loomis en 1870 describe una peritonitis como resultante de una diverticulitis (45.

    En 1877 Ball describió la anatomía patológica de la enfermedad y presentó dos casos de fístula colovesical debidas a diverticulitis (9. Cripps en 1.888 popularizó la colostomía de desviación como tratamiento para la fístula colovesical(18...

  19. A modified per os double contrast examination of the colon in the elderly

    Energy Technology Data Exchange (ETDEWEB)

    Papadaki, P.J. (Radiology Department, NIMTS General Hospital, Athens, and Radiology Department, Medical School, University of Patras (Greece)); Vassiliou, P.M. (Radiology Department, NIMTS General Hospital, Athens, and Radiology Department, Medical School, University of Patras (Greece)); Zavras, G.M. (Radiology Department, NIMTS General Hospital, Athens, and Radiology Department, Medical School, University of Patras (Greece)); Kounis, N.G. (Radiology Department, NIMTS General Hospital, Athens, and Radiology Department, Medical School, University of Patras (Greece)); Hadjioannou, N. (Radiology Department, NIMTS General Hospital, Athens, and Radiology Department, Medical School, University of Patras (Greece)); Fezoulidis, I.B. (Radiology Department, NIMTS General Hospital, Athens, and Radiology Department, Medical School, University of Patras (Greece)); Manolakis, P. (Radiology Department, NIMTS General Hospital, Athens, and Radiology Department, Medical School, University of Patra

    1993-04-01

    A modified per os double contrast examination of the colon was used in 62 elderly patients in whom conventional barium enema had been unsuccessful. We created endogenous gas generation instead of air insufflation by per os administration of a special mixture containing barium sulftate, lactulose and gastrographin. Good quality double contrast images of the colon were obtained after 12 hours in 59 of the 62 patients. The sensitivity of the method was 100% in 6 patients suffering from carcinoma and in 15 patients suffering from diverticular disease. However, the method failed to demonstrate small solitary polyps in 5 patients and it was also negative in another 27 patients. 7 of these had negative endoscopy and in the remaining a definite diagnosis was not established by any other method. It seems that this method may become an alternative for investigation of suspected colonic pathology in the elderly patients with difficulty in retaining the barium enema. (orig.)

  20. Distant Ureteral Metastasis from Colon Adenocarcinoma: Report of a Case and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Ferakis Nikolaos

    2014-01-01

    Full Text Available Carcinomas arising from organs neighbouring the ureter can directly infiltrate the ureter. Distant ureteral metastasis from colon adenocarcinoma is extremely rare and usually an incidental finding in performed autopsies. We report a case of a right ureteral metastasis in a 65-year-old Caucasian male with a history of rectal cancer for which he had been treated 4 years before. He presented with asymptomatic moderate right hydronephrosis. The patient underwent a right nephroureterectomy. Histology of the ureter revealed transmural adenocarcinoma with infiltration of the mucosa. Infiltration of the muscular coat of the bladder was found 2 years later. Thus, cystectomy and left ureterocutaneostomy were performed. The patient died 6 months later due to toxic megacolon during chemotherapy. The differential diagnosis of ureteral adenocarcinoma, especially in patients with previous history of colon adenocarcinoma, should include the possibility of distant metastasis from the primary colonic tumor.

  1. Inhibition of Colonic Tumor Growth by the Selective SGK Inhibitor EMD638683

    Directory of Open Access Journals (Sweden)

    Syeda T. Towhid

    2013-09-01

    Full Text Available Background: The serum and glucocorticoid inducible kinase SGK1, which was originally cloned from mammary tumor cells, is highly expressed in some but not all tumors. SGK1 confers survival to several tumor cells. Along those lines, the number of colonic tumors following chemical carcinogenesis was decreased in SGK1 knockout mice. Recently, a highly selective SGK inhibitor (EMD638683 has been developed. The present study explored whether EMD638683 affects survival of colon carcinoma cells in vitro and impacts on development of colonic tumors in vivo. Methods: Colon carcinoma (Caco-2 cells were exposed to EMD638683 with or without exposure to radiation (3 Gray and cell volume was estimated from forward scatter, phosphatidylserine exposure from annexin V binding, mitochondrial potential from JC-9 fluorescence, caspase 3 activity from CaspGlow Fluorescein staining, DNA degradation from propidium iodide staining as well as late apoptosis from annexin-V FITC and propidium iodide double staining. In vivo tumor growth was determined in wild type mice subjected to chemical carcinogenesis (intraperitoneal injection of 20 mg/kg 1,2-dimethylhydrazine followed by three cycles of 30 g/L synthetic dextran sulfate sodium in drinking water for 7 days. Results: EMD638683 treatment significantly augmented the radiation-induced decrease of forward scatter, increase of phosphatidylserine exposure, decrease of mitochondrial potential, increase of caspase 3 activity, increase of DNA fragmentation and increase of late apoptosis. The in vivo development of tumors following chemical carcinogenesis was significantly blunted by treatment with EMD638683. Conclusions: EMD638683 promotes radiation-induced suicidal death of colon tumor cells in vitro and decreases the number of colonic tumors following chemical carcinogenesis in vivo.

  2. Spontaneous regression of colon cancer.

    Science.gov (United States)

    Kihara, Kyoichi; Fujita, Shin; Ohshiro, Taihei; Yamamoto, Seiichiro; Sekine, Shigeki

    2015-01-01

    A case of spontaneous regression of transverse colon cancer is reported. A 64-year-old man was diagnosed as having cancer of the transverse colon at a local hospital. Initial and second colonoscopy examinations revealed a typical cancer of the transverse colon, which was diagnosed as moderately differentiated adenocarcinoma. The patient underwent right hemicolectomy 6 weeks after the initial colonoscopy. The resected specimen showed only a scar at the tumor site, and no cancerous tissue was proven histologically. The patient is alive with no evidence of recurrence 1 year after surgery. Although an antitumor immune response is the most likely explanation, the exact nature of the phenomenon was unclear. We describe this rare case and review the literature pertaining to spontaneous regression of colorectal cancer. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Crenarchaeota colonize terrestrial plant roots.

    Science.gov (United States)

    Simon, H M; Dodsworth, J A; Goodman, R M

    2000-10-01

    Microorganisms that colonize plant roots are recruited from, and in turn contribute substantially to, the vast and virtually uncharacterized phylogenetic diversity of soil microbiota. The diverse, but poorly understood, microorganisms that colonize plant roots mediate mineral transformations and nutrient cycles that are central to biosphere functioning. Here, we report the results of epifluorescence microscopy and culture-independent recovery of small subunit (SSU) ribosomal RNA (rRNA) gene sequences showing that members of a previously reported clade of soil Crenarchaeota colonize both young and senescent plant roots at an unexpectedly high frequency, and are particularly abundant on the latter. Our results indicate that non-thermophilic members of the Archaea inhabit an important terrestrial niche on earth and direct attention to the need for studies that will determine their possible roles in mediating root biology.

  4. Chromophobe Renal Cell Carcinoma.

    Directory of Open Access Journals (Sweden)

    Jyotsna Vijaykumar Wader

    2013-04-01

    Full Text Available Renal cell carcinoma is the most common neoplasm of the kidney comprised of different histological variants. Chromophobe renal cell carcinoma (ChRCC is a rare subtype of renal cell carcinoma (RCC mainly diagnosed in the sixth decade of life. It is important to identify this entity because it has significantly better prognosis than the clear cell (conventional and papillary renal cell carcinomas. The chromophobe renal cell carcinoma should be differentiated from oncocytoma and clear cell carcinoma. We report a case of a 70 year-old male who presented with a six month history of hematuria, left sided flank pain and a palpable non-tender lump in the left lumbar region. On radiology, the possibility of a left renal neoplasm was raised. A left radical nephrectomy was done and histopathological diagnosis of Type 2 (mixed chromophobe renal cell carcinoma was given. We present this case owing to its relative rarity of incidence, difficulties encountered and differential diagnoses to be considered during diagnosis as the prognosis and management protocols differ with different variants.

  5. Neurological manifestation of colonic adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Uzair Chaudhary

    2012-04-01

    Full Text Available Paraneoplastic neurologic disorders are extremely rare in cancer patients and are most commonly associated with certain tumors, such as ovarian cancer, small cell lung cancer, and breast cancer. We report here a paraneoplastic neurological syndrome in a 53-year-old man with colonic adenocarcinoma with a solitary liver metastasis. His paraneoplastic syndrome was successfully treated by methylprednisolone and primary oncologic therapies including neoadjuvant chemotherapy and definitive surgery. This is also the first documented case of simultaneous manifestation of a sensory neuropathy and limbic encephalitis with colon cancer.

  6. Colon bypass with a colon-flap augmentation ...

    African Journals Online (AJOL)

    pharynx) is a severe injury with limited surgical options. We adopted augmentation of the cicatrized upper aero-digestive tract with colon as our preferred management option. The aim of this report is to describe our initial experience with the ...

  7. MALToma of the Transverse colon, Ascending colon and Caecum: A ...

    African Journals Online (AJOL)

    Background The stomach is the most common site formucosa - associated lymphoid tissue [MALT] lymphoma (MALToma). MALToma of the colon is a rare occurrence. It is on this background that we report this case. Methods The case records a patient with a MALT lymphoma and a review of the literature on the subject ...

  8. Rapid effects of phytoestrogens on human colonic smooth muscle are mediated by oestrogen receptor beta.

    LENUS (Irish Health Repository)

    Hogan, A M

    2012-02-01

    Epidemiological studies have correlated consumption of dietary phytoestrogens with beneficial effects on colon, breast and prostate cancers. Genomic and non-genomic mechanisms are responsible for anti-carcinogenic effects but, until now, the effect on human colon was assumed to be passive and remote. No direct effect on human colonic smooth muscle has previously been described. Institutional research board approval was granted. Histologically normal colon was obtained from the proximal resection margin of colorectal carcinoma specimens. Circular smooth muscle strips were microdissected and suspended under 1g of tension in organ baths containing oxygenated Krebs solution at 37 degrees C. After an equilibration period, tissues were exposed to diarylpropionitrile (DPN) (ER beta agonist) and 1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT) (ER alpha agonist) or to the synthetic phytoestrogen compounds genistein (n=8), daidzein (n=8), fisetin (n=8) and quercetin (n=8) in the presence or absence of fulvestrant (oestrogen receptor antagonist). Mechanism of action was investigated by inhibition of downstream pathways. The cholinergic agonist carbachol was used to induce contractile activity. Tension was recorded isometrically. Phytoestrogens inhibit carbachol-induced colonic contractility. In keeping with a non-genomic, rapid onset direct action, the effect was within minutes, reversible and similar to previously described actions of 17 beta oestradiol. No effect was seen in the presence of fulvestrant indicating receptor modulation. While the DPN exerted inhibitory effects, PPT did not. The effect appears to be reliant on a p38\\/mitogen activated protein kinase mediated induction of nitric oxide production in colonic smooth muscle. The present data set provides the first description of a direct effect of genistein, daidzein, fisetin and quercetin on human colonic smooth muscle. The presence of ER in colonic smooth muscle has been functionally proven and the beta

  9. Lacrimal gland ductal carcinomas

    DEFF Research Database (Denmark)

    Andreasen, Simon; Grauslund, Morten; Heegaard, Steffen

    2017-01-01

    PURPOSE: Ductal carcinomas (DCs) of the lacrimal gland are very rare but aggressive malignancies. We investigated DC of the lacrimal gland for potentially clinically actionable targets in the search for new therapeutic options. METHODS: Case 1: A 77-year-old man, presented with diplopia...... HER2 amplification was found in cases 2 and 3. CONCLUSION: This study identified a spectrum of genetic events and pattern of protein expression in DC of the lacrimal gland similar to a subset of carcinomas of the breast and ductal carcinomas of the salivary glands. For therapeutic purposes...

  10. Coiled Descending Colon with Persistent Mesocolon and a Straight Sigmoid Colon – An Unique Congenital Anomaly

    Directory of Open Access Journals (Sweden)

    Satheesha Nayak B

    2016-07-01

    Full Text Available Descending colon is a retroperitoneal part of colon extending from left colic flexure to the brim of pelvis. Rarely does it have a mesocolon. Descending colon is most commonly affected by ulcerative colitis, Crohn’s disease and colon cancer. In the present case, cadaveric dissection of abdomen revealed a rare variation of descending colon. The descending colon had a mesocolon and was coiled in its lower part. The sigmoid colon was straight and displaced to a median position. Position of colon as in the present case might be asymptomatic, but can lead to volvulus formation, intestinal obstruction, constipation along with abdominal pain and pose a difficulty in radiological diagnosis and interpretation. Colonoscopy may not be advisable in such cases as the colonoscope may not pass through coiled descending colon and any forced attempt may pierce the wall of colon. This is the first case report of the coiled descending colon with a potential clinical importance.

  11. Treatment Options (by Stage) for Colon Cancer

    Science.gov (United States)

    ... Colorectal Cancer Colorectal Cancer Screening Research Colon Cancer Treatment (PDQ®)–Patient Version General Information About Colon Cancer ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment ...

  12. Breast and Colon Cancer Family Registries

    Science.gov (United States)

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

  13. Colonic dysfunction during cholera infection

    NARCIS (Netherlands)

    Speelman, P.; Butler, T.; Kabir, I.; Ali, A.; Banwell, J.

    1986-01-01

    To study the function of the colon in cholera, 12 patients with acute cholera diarrhea were subjected to measurements of ileocecal flow rates, fecal flow rates, and ionic compositions of stool and ileocecal fluid. Subtraction of fecal flow rates from ileocecal flow rates was taken as a measure of

  14. Salivary mucoepidermoid carcinoma revisited

    NARCIS (Netherlands)

    Coca-Pelaz, A.; Rodrigo, J.P.; Triantafyllou, A.; Hunt, J.L.; Rinaldo, A.; Strojan, P.; Haigentz, M., Jr.; Mendenhall, W.M.; Takes, R.P.; Poorten, V. Van der; Ferlito, A.

    2015-01-01

    Clinicopathological features, prognosis and therapeutic strategies for mucoepidermoid carcinoma originating in salivary and salivary-type glands of the head and neck are reviewed. We emphasise histopathological aspects, appraise the value of histochemistry, electron microscopy, immunohistochemistry

  15. MEDULLARY THYROID CARCINOMA

    Directory of Open Access Journals (Sweden)

    V. S. Medvedev

    2013-01-01

    Full Text Available Medullary thyroid carcinoma belongs to orphan diseases affecting a small part of the population. Multicenter trials are required to elaborate a diagnostic algorithm, to define treatment policy, and to predict an outcome.

  16. Thyroid cancer - papillary carcinoma

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000331.htm Thyroid cancer - papillary carcinoma To use the sharing features on ... the lower neck. Causes About 80% of all thyroid cancers diagnosed in the United States are the papillary ...

  17. Hepatocellular carcinoma and lifestyles.

    Science.gov (United States)

    Saran, Uttara; Humar, Bostjan; Kolly, Philippe; Dufour, Jean-François

    2016-01-01

    The majority of hepatocellular carcinoma occurs over pre-existing chronic liver diseases that share cirrhosis as an endpoint. In the last decade, a strong association between lifestyle and hepatocellular carcinoma has become evident. Abundance of energy-rich food and sedentary lifestyles have caused metabolic conditions such as obesity and diabetes mellitus to become global epidemics. Obesity and diabetes mellitus are both tightly linked to non-alcoholic fatty liver disease and also increase hepatocellular carcinoma risk independent of cirrhosis. Emerging data suggest that physical activity not only counteracts obesity, diabetes mellitus and non-alcoholic fatty liver disease, but also reduces cancer risk. Physical activity exerts significant anticancer effects in the absence of metabolic disorders. Here, we present a systematic review on lifestyles and hepatocellular carcinoma. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  18. Colonic urticaria pattern due to early ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Greenberg, H.M.; Goldberg, H.I.; Axel, L.

    1981-05-15

    The unusual radiographic pattern of bleb-like mounds on the surface of the colon mucosa, previously described as colonic urticaria, was seen in 3 patients in whom no allergic state was present. This urticaria-like pattern was due to colonic distention in all 3, and represented only submucosal edema on the gross and microscopic specimens. We hypothesize that this pattern is due to early changes of ischemia caused by colon distention.

  19. Papillary thyroid carcinoma

    DEFF Research Database (Denmark)

    Godballe, C; Asschenfeldt, P; Sørensen, J A

    1994-01-01

    The age influence on the prognosis of papillary thyroid carcinoma was analyzed in a group of 67 patients. A marked decline in cause-specific survival was found for patients older than 60 years of age at the time of diagnosis. In order to find a tumor-biological explanation of the prognostic...... invasion and distant metastases. The results indicate that 60 years of age the time of diagnosis may be the "prognostic break-point" for papillary thyroid carcinoma....

  20. Cryotherapy for hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Awad, Tahany; Thorlund, Kristian; Gluud, Christian

    2009-01-01

    BACKGROUND: Hepatocellular carcinoma is the most common primary malignant cancer of the liver. Evidence for the role of cryotherapy in the treatment of hepatocellular carcinoma is controversial. OBJECTIVES: The aim of this review is to evaluate the potential benefits and harms of cryotherapy...... national and topic-specific databases, bibliographies, conference abstracts, journals, and grey literature. Furthermore, we reviewed the reference lists and contacted the principal authors of the identified studies. SELECTION CRITERIA: Randomised clinical trials (irrespective of language or publication...

  1. Analysis of APC allelic imbalance/loss of heterozygosity and APC protein expression in cutaneous squamous cell carcinomas.

    LENUS (Irish Health Repository)

    Gray, Sarah E

    2011-05-01

    The adenomatous polyposis coli (APC) gene is a tumor suppressor gene which is mutated in the hereditary disease, familial adenomatous polyposis (FAP). Somatic mutations of the APC gene have also been identified in the majority of sporadic colorectal carcinomas, and mutation of the APC gene appears to be an early step in the initiation of colon cancer. Loss of heterozygosity (LOH) of APC has been described in a variety of other cancer types, including renal cell carcinoma, gastric cancer, non-small cell lung cancer, endometrial cancer and oral squamous cell carcinomas (SCC).

  2. [Pulmonary sarcomatoid carcinoma].

    Science.gov (United States)

    Antoine, Martine; Vieira, Thibault; Fallet, Vincent; Hamard, Cécile; Duruisseaux, Michael; Cadranel, Jacques; Wislez, Marie

    2016-01-01

    Pulmonary sarcomatoid carcinomas are a rare group of tumors accounting for about one percent of non-small cell lung carcinoma (NSCLC). In 2015, the World Health Organization classification united under this name all the carcinomas with sarcomatous-like component with spindle cell or giant cell appearance, or associated with a sarcomatous component sometimes heterologous. There are five subtypes: pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma and pulmonary blastoma. Clinical characteristics are not specific from the other subtypes of NSCLC. Epithelial to mesenchymal transition pathway may play a key role. Patients, usually tobacco smokers, are frequently symptomatic. Tumors are voluminous more often peripherical than central, with strong fixation on FDG TEP CT. Distant metastases are frequent with atypical visceral locations. These tumors have poorer prognosis than the other NSCLC subtypes because of great aggressivity, and frequent chemoresistance. Here we present pathological description and a review of literature with molecular features in order to better describe these tumors and perhaps introduce new therapeutics. Copyright © 2016. Published by Elsevier Masson SAS.

  3. Oral squamous cell carcinoma around dental implants.

    Science.gov (United States)

    Czerninski, Rakefet; Kaplan, Ilana; Almoznino, Galit; Maly, Alexander; Regev, Eran

    2006-10-01

    It is well documented that oral squamous cell carcinoma (OSCC) is related to risk factors such as smoking and alcohol consumption as well as premalignant lesions and conditions such as leukoplakia, oral lichen planus (OLP), and previous malignancy of the upper respiratory system and gastrointestinal tract. Osseointegrated dental implants are rarely reported in association with OSCC. This article presents 2 cases of OSCC adjacent to dental implants in patients at risk for oral cancer--1 was a heavy smoker with OLP; the other had a history of previous oral and colon cancer. Six additional cases of malignancy adjacent to dental implants were retrieved from the literature; the majority of cases had at least 1 recognized risk factor for oral cancer. Although such cases are rarely reported, patients at risk for oral cancer, especially those with multiple existing risk factors, that present with failing dental implants should be thoroughly evaluated to rule out the presence of malignancy disguised as peri-implant disease.

  4. Congenital Diverticular Disease of the Entire Colon

    Directory of Open Access Journals (Sweden)

    A. Patel

    2013-01-01

    Full Text Available Congenital or true colonic diverticulosis is a rare condition typified by the preservation of the colonic wall architecture within the diverticular outpouching. Cases of multiple jejunal diverticula have been reported as well as cases of solitary giant diverticula of the colon. There have been no reports in the literature of pancolonic congenital diverticulosis.

  5. CALCIUM AND THE PREVENTION OF COLON CANCER

    NARCIS (Netherlands)

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

    1991-01-01

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

  6. Colonization of peripheral intravascular catheters with biofilm ...

    African Journals Online (AJOL)

    Background: Biofilms often colonize catheters and contribute to catheter-related septicemia. However, predictors of catheter colonization by biofilms remain poorly defined. The aim of this study was to evaluate clinical factors that may be associated with biofilm colonization of catheters. Materials and Methods: A total of 54 ...

  7. Different effects of ERβ and TROP2 expression in Chinese patients with early-stage colon cancer.

    Science.gov (United States)

    Fang, Yu-Jing; Wang, Guo-Qiang; Lu, Zhen-Hai; Zhang, Lin; Li, Ji-Bin; Wu, Xiao-Jun; Ding, Pei-Rong; Ou, Qing-Jian; Zhang, Mei-Fang; Jiang, Wu; Pan, Zhi-Zhong; Wan, De-Sen

    2012-12-01

    Estrogen receptor beta (ERβ) and TROP2 expressed in colon carcinoma and might play an important role there. We explored the relationship of ERβ and TROP2 expression with the prognosis of early-stage colon cancer. ERβ and TROP2 levels were assessed by immunohistochemistry in normal mucosa and tumoral tissues from 220 Chinese patients with T(3)N(0)M(0) (stage IIa) and T(4)N(0)M(0) (stage IIb) colon cancer in the Cancer Center, Sun Yat-sen University, who underwent curative surgical resection between 1995 and 2003. The Cox proportional hazards regression model was applied to analyze the overall survival (OS) data, and the ROC curve, Kaplan-Meier estimate, log rank test, and Jackknife method were used to show the effect of ERβ and TROP2 expression at different stages of cancer. The 5-year survival rates were not significantly different between the patients with stage IIa and stage IIb colon cancer (83 vs. 80 %, respectively). The high expression of ERβ was related to decreasing OS in stage IIa and stage IIb colon cancer, while the high expression of TROP2 was related to decreasing OS in stage IIb colon cancer. The expression of ERβ and TROP2 has tumor-suppressive and tumor-promoting effect in stage IIa and stage IIb colon cancer, respectively.

  8. Olive oil, other seasoning fats, and the risk of colorectal carcinoma.

    Science.gov (United States)

    Braga, C; La Vecchia, C; Franceschi, S; Negri, E; Parpinel, M; Decarli, A; Giacosa, A; Trichopoulos, D

    1998-02-01

    An association between fats and colorectal carcinoma has been suggested, but the epidemiologic evidence by type of dietary fat is far less clear. Colorectal carcinoma rates have been relatively low in Mediterranean countries compared with most other Western countries, but the components of the Mediterranean diet responsible for this favorable pattern are unclear. The relationship between various added (seasoning) fats and colorectal carcinoma risk was investigated using data from a case-control study conducted between January 1992 and June 1996 in six Italian areas. Cases were 1953 patients with incident, histologically confirmed colorectal carcinoma (1225 of the colon and 728 of the rectum) admitted to the major teaching and general hospitals in the study areas. Controls were 4154 subjects with no history of cancer who were admitted to hospitals in the same catchment areas for acute, nonneoplastic diseases unrelated to the the digestive tract and requiring no long term modifications of diet. Dietary habits were investigated using a validated food frequency questionnaire including 78 items. Lipid intake was estimated by taking into account the content of seasoning lipids in different dishes, the frequency of consumption and portion size of each dish, and individual fat intake patterns. The odds ratios (OR) for successive tertiles of olive oil intake, compared with the lowest one, were 0.87 (95% confidence interval [CI], 0.75-1.01) and 0.83 (95% CI, 0.70-0.99) (chi2trend = 4.49, P = 0.03) when colorectal carcinoma was analyzed as a whole, 0.82 (95% CI, 0.68-0.98) and 0.81 (95% CI, 0.66-0.99) (chi2trend = 4.05, P = 0.04) for colon carcinoma, and 0.96 (95% CI, 0.77-1.19) and 0.88 (95% CI, 0.66-1.12) for rectal carcinoma. For specific seed oils (including sunflower, maize, peanut, and soya), the OR for colorectal carcinoma was 0.91 in the highest tertile of intake, and the corresponding values were 1.01 for mixed seed oils and 0.93 for butter. None of these estimates

  9. Structure-activity relationships of highly cytotoxic copper(II) complexes with modified indolo[3,2-c]quinoline ligands.

    Science.gov (United States)

    Primik, Michael F; Göschl, Simone; Jakupec, Michael A; Roller, Alexander; Keppler, Bernhard K; Arion, Vladimir B

    2010-12-06

    A number of indolo[3,2-c]quinolines were synthesized and modified at the lactam unit to provide a peripheral binding site able to accommodate metal ions. Potentially tridentate ligands HL(1a)-HL(4a) and HL(1b)-HL(4b) were reacted with copper(II) chloride in isopropanol/methanol to give novel five-coordinate copper(II) complexes [Cu(HL(1a-4a))Cl(2)] and [Cu(HL(1b-4b))Cl(2)]. In addition, a new complex [Cu(HL(5b))Cl(2)] and two previously reported compounds [Cu(HL(6a))Cl(2)] and [Cu(HL(6b))Cl(2)] with modified paullone ligands HL(5b), HL(6a), and HL(6b), which can be regarded as close analogues of indoloquinolines HL(1b), HL(4a), and HL(4b), in which the pyridine ring was formally substituted by a seven-membered azepine ring, were synthesized for comparison. The new ligands and copper(II) complexes were characterized by (1)H and (13)C NMR, IR and electronic absorption spectroscopy, ESI mass spectrometry, magnetic susceptibility measurements in solution at 298 K ([Cu(HL(1a))Cl(2)] and [Cu(HL(4b))Cl(2)]), and X-ray crystallography ([Cu(HL(3b))Cl(2)]·3DMF, [Cu(HL(4b))Cl(2)]·2.4DMF, HL(5b) and [Cu(HL(5b))Cl(2)]·0.5CH(3)OH). All complexes were tested for cytotoxicity in the human cancer cell lines CH1 (ovarian carcinoma), A549 (non-small cell lung cancer), and SW480 (colon carcinoma). The compounds are highly cytotoxic, with IC(50) values ranging from nanomolar to very low micromolar concentrations. Substitution of the seven-membered azepine ring in paullones by a pyridine ring resulted in a six- to nine-fold increase of cytotoxicity in SW480 cells. Electron-releasing or electron-withdrawing substituents in position 8 of the indoloquinoline backbone do not exert any effect on cytotoxicity of copper(II) complexes, whereas copper(II) compounds with Schiff bases obtained from 2-acetylpyridine and indoloquinoline hydrazines are 10 to 50 times more cytotoxic than those with ligands prepared from 2-formylpyridine and indoloquinoline hydrazines.

  10. Flagellin Induces β-Defensin 2 in Human Colonic Ex vivo Infection with Enterohemorrhagic Escherichia coli.

    Science.gov (United States)

    Lewis, Steven B; Prior, Alison; Ellis, Samuel J; Cook, Vivienne; Chan, Simon S M; Gelson, William; Schüller, Stephanie

    2016-01-01

    Enterohemorrhagic E.coli (EHEC) is an important foodborne pathogen in the developed world and can cause life-threatening disease particularly in children. EHEC persists in the human gut by adhering intimately to colonic epithelium and forming characteristic attaching/effacing lesions. In this study, we investigated the innate immune response to EHEC infection with particular focus on antimicrobial peptide and protein expression by colonic epithelium. Using a novel human colonic biopsy model and polarized T84 colon carcinoma cells, we found that EHEC infection induced expression of human β-defensin 2 (hBD2), whereas hBD1, hBD3, LL-37, and lysozyme remained unchanged. Infection with specific EHEC deletion mutants demonstrated that this was dependent on flagellin, and apical exposure to purified flagellin was sufficient to stimulate hBD2 and also interleukin (IL)-8 expression ex vivo and in vitro. Flagellin-mediated hBD2 induction was significantly reduced by inhibitors of NF-κB, MAP kinase p38 and JNK but not ERK1/2. Interestingly, IL-8 secretion by polarized T84 cells was vectorial depending on the side of stimulation, and apical exposure to EHEC or flagellin resulted in apical IL-8 release. Our results demonstrate that EHEC only induces a modest immune response in human colonic epithelium characterized by flagellin-dependent induction of hBD2 and low levels of IL-8.

  11. Is there any association between colonic polyps and gastric intestinal metaplasia?

    Science.gov (United States)

    Ünler, Gülhan Kanat; Teke Özgür, Gülsüm; Göktürk, Hüseyin Savaş; Korkmaz, Hüseyin; Erinanç, Özgür Hilal

    2016-05-01

    Chronic gastritis progression is a multistep process of atrophy, intestinal metaplasia (IM), and dysplasia, which may lead to invasive carcinoma. In this study, we identified an association of colonic polyps with gastric IM in patients undergoing colonoscopy. This retrospective case-control, cross-sectional study was conducted in a tertiary-care institution in Turkey. Pathology and endoscopy reports were reviewed. The study group comprised 400 patients with colonic adenomatous polyps, and the control group comprised 360 patients without colonic adenomatous polyps on colonoscopy. The risk of gastric IM was 1.42-fold higher in the study group (pfolder higher than that in the control group (p<0.05). H. pylori infection prevalence was higher only in patients with high-grade colonic polyp dysplasia (p<0.05). There were no statistically significant differences in the proportion of incomplete IM between the groups (p<0.05). This study observed increased rates of gastric IM with colonic polyps. An increased risk of gastric IM was associated with higher grades of polyp dysplasia.

  12. Carcinoma medular do rim Renal medullary carcinoma

    Directory of Open Access Journals (Sweden)

    Paulo Guilherme de Oliveira Salles

    2006-04-01

    Full Text Available É relatado caso de paciente de 24 anos, portador de traço falciforme, com imagem sólida no rim direito, submetido a nefrectomia radical que revelou tumor, cujo exame anatomopatológico permitiu o diagnóstico de carcinoma medular do rim. Os autores discutem aspectos dessa neoplasia, tais como freqüência, patogênese, apresentação clínica, histopatologia e evolução.We report the case of a 24-year-old patient who presented a left kidney tumor that was diagnosed as a medullary renal cell carcinoma. The following aspects of this neoplasia are discussed in this communication: frequency, pathogenesis, clinical presentation, histopathological findings, differential diagnosis and follow-up.

  13. Hericium erinaceus (Lion’s Mane) mushroom extracts inhibit metastasis of cancer cells to the lung in CT-26 colon cancer-transplanted mice

    Science.gov (United States)

    We investigated the anti-metastatic activity of four Hericium erinaceus edible mushroom extracts using CT-26 murine colon carcinoma cells as an indicator of inhibition of cell migration to the lung. Hot water (HWE) and microwaved 50% ethanol (MWE) extracts of Hericium erinaceus strongly elicited ca...

  14. Colonic Interposition in a Woman with Attenuated Familial Adenomatous Polyposis: Does the Location of the Colon Affect Polyp Formation?

    Directory of Open Access Journals (Sweden)

    Melanie D Beaton

    2008-01-01

    Full Text Available Attenuated familial adenomatous polyposis (AFAP is a rare but well-established cause of colorectal carcinoma and multiple polyps. The present paper describes a case of a woman diagnosed with colorectal cancer at 34 years of age and subsequently found to have AFAP by genetic testing. During infancy, the patient underwent surgical correction of esophageal atresia with colonic interposition. While she had developed adenomatous polyps in her native cecum, there was no evidence of polyps or cancer in the segment of large intestine interposed between her upper esophagus and stomach. Therefore, various environmental differences between the upper and lower gastrointestinal tract may play a role in the expression of AFAP phenotype.

  15. [Regional growth preferences in hereditary, synchronous, and metachronous colorectal carcinomas. Basics of tumor surgery Part II].

    Science.gov (United States)

    Stelzner, F

    2006-11-01

    This article discusses the therapeutic importance of the loss of self-regulation of cell division in polypoid adenomas and in the cloacogenic, cancerophilic rectal segment. Regional growth preferences can observed in familial adenomatous polyposis (FAP) and ulcerative colitis, as in other diseases featuring a cancerous disposition on the mucosa. For example, rectal carcinomas are more common than colon carcinomas if one considers the total mucosal surface area at risk. Malignant changes do not occur randomly in existing adenomas of FAP patients, and the adenomas' cell division--as in other adenomas--is governed by some degree of self-regulation. In FAP patients undergoing proctocolectomy, preferred new growth areas for carcinomas include the duodenum and ileum. In patients with synchronous colorectal cancers, the rectum is more commonly affected than other colon segments. If the rectum is resected, metachronous carcinomas are exceedingly rare in the remaining colon segments. Clinical decisions about rectal resection must be informed by understanding of the importance of this organ for anorectal continence as well as the described growth of colorectal malignancies.

  16. [Breast carcinoma metastasis into a renal cell carcinoma].

    Science.gov (United States)

    Perrin, Christophe; Talarmin, Marie; Fontaine, Aurélie; Kerbrat, Pierre; Audrain, Odile; Rioux-Leclercq, Nathalie; Chiforeanu, Dan Cristian

    2011-10-01

    We report the case of a patient carrying a right breast carcinoma whose imaging exams showed lung and bone metastasic release, and incidentally synchronous right renal tumor. Histologic examination of the renal tumor found a mammary carcinoma metastasis into a clear renal cell carcinoma. This is the second case report of breast cancer with metastasis in a resected renal clear cell carcinoma. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  17. Synchronous thyroid carcinoma and squamous cell carcinoma. A case report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jae Seo [Chonnam National Univ. School of Dentistry, Kwangju (Korea, Republic of)

    2006-12-15

    Thyroid carcinoma occurring as a second primary associated with head and neck squamous cell carcinoma (SCC) is unusual. This report presents a synchronous thyroid carcinoma and squamous cell carcinoma in the anterior palate region of a 41-year-old man. The clinical, radiologic, and histologic features are described. At 10-month follow-up after operation, no evidence of recurrence ana metastasis was present.

  18. Early onset sebaceous carcinoma

    Directory of Open Access Journals (Sweden)

    Kaltreider Sara A

    2011-09-01

    Full Text Available Abstract Background Ocular sebaceous carcinoma can masquerade as benign lesions resulting in delay of diagnosis. Early recognition is even more difficult in young patients where the disease rarely occurs. Here, we provide a clinicopathological correlation of ocular sebaceous carcinoma in a young individual lacking history of hereditary cancer or immunosuppression. Findings A detailed histopathological study including p53 DNA sequencing was performed on an aggressive sebaceous carcinoma presenting in a healthy 32 year-old Caucasian woman. She had no history of retinoblastoma, evidence for a hereditary cancer syndrome, or radiation therapy. However, she potentially was at risk for excessive UV light exposure. A detailed review of the literature is also provided. A moderately well differentiated sebaceous carcinoma was established histopathologically arising from the meibomian gland of the upper eyelid. In most areas, the cytoplasm contained small but distinct Oil-red-O positive vacuoles. Direct sequencing of p53 identified a G:C→A:T mutation at a dipyrimidine site. The mutation results in substitution of arginine for the highly conserved glycine at residue 199 located at the p53 dimer-dimer interface. Energy minimization structural modeling predicts that G199R will neutralize negative charges contributed by nearby inter- and intramonomeric glutamate residues. Discussion This study points to the importance of recognizing that sebaceous carcinoma can occur in young patients with no evidence for hereditary cancer risk or radiation therapy. The G199R substitution is anticipated to alter the stability of the p53 tetrameric complex. The role of UV light in the etiology of sebaceous carcinoma deserves further study. Our findings, taken together with those of others, suggest that different environmental factors could lead to the development of sebaceous carcinoma in different patients.

  19. [Sarcomatoid renal cell carcinoma].

    Science.gov (United States)

    Arnoux, V; Lechevallier, E; Pamela, A; Long, J-A; Rambeaud, J-J

    2013-06-01

    The objective was to perform a systematic review of literature concerning epidemiology, clinical and biological data, prognosis and therapy of sarcomatoid renal cell carcinomas. Data on sarcomatoid renal cell carcinomas have been sought by querying the server Medline with MeSH terms following or combination of them: "renal carcinoma", "renal cell carcinoma," "renal cancer", "sarcomatoid" "sarcomatoid transformation" and "sarcomatoid differentiation." The articles obtained were selected according to their methodology, the language in English or French, the relevance and the date of publication. Twenty papers were selected. According to the literature, a sarcomatoid contingent can be observed in all subtypes of renal cell carcinomas, with a frequency of 1 to 15% of cases. The median age at diagnosis was 60 years with a majority of symptomatic patients (90%), mainly with abdominal pain and hematuria. These tumors were often found in patients with locally advanced or metastatic (45-77%). The imaging was not specific for the diagnosis and biopsy had a low sensitivity for identifying a sarcomatoid contingent. The treatment was based on a combination of maximal surgical resection whenever possible and systemic therapy for metastastic disease. Pathological data often showed large tumors, Furhman 4 grades, combined biphasic carcinomatous contingent (clear cell carcinoma in most cases) and sarcomatoid. Genetically, there was no specific abnormality but a complex association of chromosomal additions and deletions. The prognosis was pejorative with a specific median survival of 5 to 19 months without any impact of the sarcomatoid contingent rate. Sarcomatoid renal cell carcinoma is a form not to ignore despite its rarity. Mainly symptomatic and discovered at an advanced stage, it has a poor prognosis, requiring multidisciplinary management quickly and correctly. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  20. Transverse loop colostomy and colonic motility.

    Science.gov (United States)

    Pucciani, F; Ringressi, M N; Maltinti, G; Bechi, P

    2014-11-01

    The motility of the defunctionalized colon, distal to transverse loop colostomy, has never been studied "in vivo." The aim of our study was to evaluate the influence of transverse loop colostomy on colonic motility. Thirteen patients were examined before stoma closure by means of clinical evaluation and colonic manometry; we studied both the right and distal colon in both fasting and fed patients in order to detect motor activity. Quantitative and qualitative manometric analyses showed that the diverted colon had motor activity even if no regular colonic motor pattern was observed. The spreading of aboral propagated contractions (PCs) was sometimes recorded from the right colon to the distal colon. The response of the proximal and distal colon to a standard meal, when compared to fasting values, increased more than 40 and 35 %, respectively. Stool and gas ejections from the colostomy were never related to a particular type of colonic motility: Motor quiescence such as PCs was chaotically related to stool escape. In conclusion, motility of the defunctionalized colon is preserved in patients with transverse loop colostomy.

  1. Ketogenic HMGCS2 Is a c-Myc target gene expressed in differentiated cells of human colonic epithelium and down-regulated in colon cancer.

    Science.gov (United States)

    Camarero, Nuria; Mascaró, Cristina; Mayordomo, Cristina; Vilardell, Felip; Haro, Diego; Marrero, Pedro F

    2006-09-01

    HMGCS2, the gene that regulates ketone body production, is expressed in liver and several extrahepatic tissues, such as the colon. In CaCo-2 colonic epithelial cells, the expression of this gene increases with cell differentiation. Accordingly, immunohistochemistry with specific antibodies shows that HMGCS2 is expressed mainly in differentiated cells of human colonic epithelium. Here, we used a chromatin immunoprecipitation assay to study the molecular mechanism responsible for this expression pattern. The assay revealed that HMGCS2 is a direct target of c-Myc, which represses HMGCS2 transcriptional activity. c-Myc transrepression is mediated by blockade of the transactivating activity of Miz-1, which occurs mainly through a Sp1-binding site in the proximal promoter of the gene. Accordingly, the expression of human HMGCS2 is down-regulated in 90% of Myc-dependent colon and rectum tumors. HMGCS2 protein expression is down-regulated preferentially in moderately and poorly differentiated carcinomas. In addition, it is also down-regulated in 80% of small intestine Myc-independent tumors. Based on these findings, we propose that ketogenesis is an undesirable metabolic characteristic of the proliferating cell, which is down-regulated through c-Myc-mediated repression of the key metabolic gene HMGCS2.

  2. Nevoid basal cell carcinoma syndrome

    Science.gov (United States)

    NBCC syndrome; Gorlin-Goltz syndrome; Basal cell nevus syndrome; BCNS; Basal cell cancer - nevoid basal cell carcinoma syndrome ... Nevoid basal cell carcinoma nevus syndrome is a rare genetic ... syndrome is known as PTCH ("patched"). The gene is passed down ...

  3. Schwannoma of the sigmoid colon

    OpenAIRE

    Çakır, Tuğrul; Aslaner, Arif; Yaz, Müjgan; Gündüz, Umut rıza

    2015-01-01

    Colonic schwannomas are very rare gastrointestinal tumours originating from Schwann cells, which form the neural sheath. Primary schwannomas of the lower gastrointestinal tract are very rare and usually benign in nature. However, if they are not surgically removed, malign degeneration can occur. We report a case of a 79-year-old woman who presented to our clinic with rectal bleeding and constipation. She underwent a lower gastrointestinal tract endoscopy. A mass subtotally obstructing the lum...

  4. Laboratory colonization of Toxorhynchites brevipalpis.

    Science.gov (United States)

    Trpis, M; Gerberg, E J

    1973-05-01

    Toxorhynchites brevipalpis, a predator on larvae of Aedes aegypti and other mosquitos, was successfully colonized in the laboratory. At 25 degrees C, embryonic development was completed within 50 hours of oviposition, while larval and pupal development together took a further 27-41 days. The adult mosquitos mated in cages as small as 15x15x15 cm, and the embryonated eggs were obtained 6-31 days after the adults emerged.

  5. Laboratory colonization of Toxorhynchites brevipalpis*

    Science.gov (United States)

    Trpis, Milan; Gerberg, Eugene J.

    1973-01-01

    Toxorhynchites brevipalpis, a predator on larvae of Aedes aegypti and other mosquitos, was successfully colonized in the laboratory. At 25°C, embryonic development was completed within 50 hours of oviposition, while larval and pupal development together took a further 27-41 days. The adult mosquitos mated in cages as small as 15×15×15 cm, and the embryonated eggs were obtained 6-31 days after the adults emerged. PMID:4149530

  6. FHL2 expression in peritumoural fibroblasts correlates with lymphatic metastasis in sporadic but not in HNPCC-associated colon cancer.

    Science.gov (United States)

    Gullotti, Lucia; Czerwitzki, Jacqueline; Kirfel, Jutta; Propping, Peter; Rahner, Nils; Steinke, Verena; Kahl, Philip; Engel, Christoph; Schüle, Roland; Buettner, Reinhard; Friedrichs, Nicolaus

    2011-12-01

    Four and a half LIM domain protein-2 (FHL2) is a component of the focal adhesion structures and has been suggested to have an important role in cancer progression. This study analyses the role of FHL2 in peritumoural fibroblasts of sporadic and hereditary non-polyposis colorectal cancer (HNPCC). Tissue specimens of 48 sporadic and 49 hereditary colon cancers, respectively, were stained immunohistochemically for FHL2, transforming growth factor (TGF)-β1 ligand and α-SMA. Myofibroblasts at the tumour invasion front co-expressed α-SMA and FHL2. Sporadic colon cancer but not HNPCC cases showed a correlation between TGF-β1 expression of the invading tumour cells and FHL2 staining of peritumoural myofibroblasts. Overexpression of FHL2 in peritumoural myofibroblasts correlated to lymphatic metastasis in sporadic colon cancer but not in HNPCC. In cultured mouse fibroblasts, TGF-β1 treatment induced myofibroblast differentiation, stimulated FHL2 protein expression and elevated number of migratory cells in transwell motility assays, suggesting that FHL2 is regulated downstream of TGF-β. Physical contact of colon cancer cells and myofibroblasts via FHL2-positive focal adhesions was detected in human colon carcinoma tissue and in co-culture assays using sporadic as well as HNPCC-derived tumour cell lines. Our data provide strong evidence for an important role of FHL2 in the progression of colon cancers. Tumour-secreted TGF-β1 stimulates FHL2 protein expression in peritumoural fibroblasts, probably facilitating the invasion of tumour glands into the surrounding tissue by enhanced myofibroblast migration and tight connection of fibroblasts to tumour cells via focal adhesions. These findings are absent in HNPCC-associated colon cancers in vivo and may contribute to a less invasive and more protruding tumour margin of microsatellite instable carcinomas.

  7. Fish oil ingestion reduces the number of aberrant crypt foci and adenoma in 1,2-dimethylhydrazine-induced colon cancer in rats

    Directory of Open Access Journals (Sweden)

    A.P.B. Moreira

    2009-12-01

    Full Text Available We determined the effect of fish oil (FO ingestion on colonic carcinogenesis in rats. Male Wistar rats received 4 subcutaneous injections (40 mg/kg body weight each of 1,2-dimethylhydrazine (DMH at 3-day intervals and were fed a diet containing 18% by weight FO (N = 10 or soybean oil (SO, N = 10 for 36 weeks. At sacrifice, the colon was removed, aberrant crypt foci were counted and the fatty acid profile was determined. Intestinal tumors were removed and classified as adenoma or carcinoma. Liver and feces were collected and analyzed for fatty acid profile. FO reduced the mean (± SEM number of aberrant crypt foci compared to SO (113.55 ± 6.97 vs 214.60 ± 18.61; P 0.05. In conclusion, our findings indicate that chronic FO ingestion protected against the DMH-induced preneoplastic colon lesions and adenoma development, but not against carcinoma in rats.

  8. Decorin in Human Colon Cancer

    Science.gov (United States)

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

    2015-01-01

    Decorin is generally recognized as a tumor suppressing molecule. Nevertheless, although decorin has been shown to be differentially expressed in malignant tissues, it has often remained unclear whether, in addition to non-malignant stromal cells, cancer cells also express it. Here, we first used two publicly available databases to analyze the current information about decorin expression and immunoreactivity in normal and malignant human colorectal tissue samples. The analyses demonstrated that decorin expression and immunoreactivity may vary in cancer cells of human colorectal tissues. Therefore, we next examined decorin expression in normal, premalignant and malignant human colorectal tissues in more detail using both in situ hybridization and immunohistochemistry for decorin. Our results invariably demonstrate that malignant cells within human colorectal cancer tissues are devoid of both decorin mRNA and immunoreactivity. Identical results were obtained for cells of neuroendocrine tumors of human colon. Using RT-qPCR, we showed that human colon cancer cell lines are also decorin negative, in accordance with the above in vivo results. Finally, we demonstrate that decorin transduction of human colon cancer cell lines causes a significant reduction in their colony forming capability. Thus, strategies to develop decorin-based adjuvant therapies for human colorectal malignancies are highly rational. PMID:26001829

  9. Early colon cancer within a diverticulum treated by magnifying chromoendoscopy and laparoscopy

    Science.gov (United States)

    Fu, Kuang I; Hamahata, Yukihiro; Tsujinaka, Yasunobu

    2010-01-01

    We report a unique case of intramucosal carcinoma in a tubulovillous adenoma arising from a single diverticulum. Endoscopic mucosal resection (EMR) was carried out successfully and completely with the assistance of laparoscopy. A 71-year-old man was admitted to our hospital because of melena and anemia. Emergent colonoscopy showed diverticulosis in the right-sided colon. However, endoscopy could not exactly detect the bleeding site. A flat elevated polyp was found within a single diverticulum located in the descending colon and diagnosed as an intramucosal carcinoma, as magnifying chromoendoscopy revealed a type IV pit pattern. As his diverticular bleeding repeated, a right-sided hemicolectomy was decided for treatment, the polyp within the diverticulum was also completely removed by EMR with the assistance of laparoscopy. Although a colonic perforation was detected immediately after EMR, the perforation was closed with endoclips intraluminally and also repaired laparoscopically from the serosal side. Histologically, the resected lesion was an intramucosal well-differentiated adenocarcinoma and the surgical margin was free of tumor. PMID:20333800

  10. Evidence for the involvement of NOD2 in regulating colonic epithelial cell growth and survival.

    Science.gov (United States)

    Cruickshank, Sheena-M; Wakenshaw, Louise; Cardone, John; Howdle, Peter-D; Murray, Peter-J; Carding, Simon-R

    2008-10-14

    To investigate the function of NOD2 in colonic epithelial cells (CEC). A combination of in vivo and in vitro analyses of epithelial cell turnover in the presence and absence of a functional NOD2 protein and, in response to enteric Salmonella typhimurium infection, were used. shRNA interference was also used to investigate the consequences of knocking down NOD2 gene expression on the growth and survival of colorectal carcinoma cell lines. In the colonic mucosa the highest levels of NOD2 expression were in proliferating crypt epithelial cells. Muramyl dipeptide (MDP), that is recognized by NOD2, promoted CEC growth in vitro. By contrast, the growth of NOD2-deficient CECs was impaired. In vivo CEC proliferation was also reduced and apoptosis increased in Nod2(-/-) mice, which were also evident following enteric Salmonella infection. Furthermore, neutralization of NOD2 mRNA expression in human colonic carcinoma cells by shRNA interference resulted in decreased survival due to increased levels of apoptosis. These findings are consistent with the involvement of NOD2 protein in promoting CEC growth and survival. Defects in proliferation by CECs in cases of CD may contribute to the underlying pathology of disrupted intestinal homeostasis and excessive inflammation.

  11. Insight On Colorectal Carcinoma Infiltration by Studying Perilesional Extracellular Matrix.

    Science.gov (United States)

    Nebuloni, Manuela; Albarello, Luca; Andolfo, Annapaola; Magagnotti, Cinzia; Genovese, Luca; Locatelli, Irene; Tonon, Giovanni; Longhi, Erika; Zerbi, Pietro; Allevi, Raffaele; Podestà, Alessandro; Puricelli, Luca; Milani, Paolo; Soldarini, Armando; Salonia, Andrea; Alfano, Massimo

    2016-03-04

    The extracellular matrix (ECM) from perilesional and colorectal carcinoma (CRC), but not healthy colon, sustains proliferation and invasion of tumor cells. We investigated the biochemical and physical diversity of ECM in pair-wised comparisons of healthy, perilesional and CRC specimens. Progressive linearization and degree of organization of fibrils was observed from healthy to perilesional and CRC ECM, and was associated with a steady increase of stiffness and collagen crosslinking. In the perilesional ECM these modifications coincided with increased vascularization, whereas in the neoplastic ECM they were associated with altered modulation of matrisome proteins, increased content of hydroxylated lysine and lysyl oxidase. This study identifies the increased stiffness and crosslinking of the perilesional ECM predisposing an environment suitable for CRC invasion as a phenomenon associated with vascularization. The increased stiffness of colon areas may represent a new predictive marker of desmoplastic region predisposing to invasion, thus offering new potential application for monitoring adenoma with invasive potential.

  12. Extramammary Paget's Disease of the Scrotum Associated with Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Yu-Ching Li

    2009-10-01

    Full Text Available Extramammary Paget's disease (EMPD is a rare cutaneous carcinoma of epidermal origin. The diagnosis is frequently delayed, and the disease tends to be associated with an underlying adnexal or internal malignancy. There have been several reports of EMPD associated with carcinoma of the bladder, prostate, kidney, and colon. The association of hepato-cellular carcinoma (HCC with EMPD appears to be exceedingly rare; to our knowledge, it has been reported only once in the English literature. Herein, we report an unusual case of EMPD of the scrotum associated with HCC. EMPD was diagnosed 1 year after the appearance of an erythematous plaque, and HCC was noted 19 months after the diagnosis of EMPD. From our experience and literature review, in patients with nonspecific skin lesions that are unresponsive to conventional treatment, EMPD should be considered and skin biopsy performed. Long-term follow-up is needed to watch for the appearance of adnexal carcinoma or internal malignancy. [J Chin Med Assoc 2009;72(10:542–546

  13. Simultaneous Laryngeal Squamous Cell Carcinoma and Papillary Thyroid Carcinoma

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    Bighan Khademi

    2011-04-01

    Full Text Available The association of squamous cell carcinoma of the larynx with thyroid papillary carcinoma is an unusual finding. From 2004 to 2011, approximately 250 patients underwent laryngectomies due to squamous cell carcinoma of the larynx at the Otolaryngology Department of Khalili Hospital, affiliated with Shiraz University of Medical Sciences, Shiraz, Iran. In three patients, synchronous occurrence of squamous cell carcinoma and thyroid papillary carcinoma was found. Histopathologic study of the lymph nodes revealed metastatic papillary thyroid carcinoma in one case. We report three cases of thyroid papillary carcinoma incidentally found on histological examinations of resected thyroid lobes, as a procedure required for treatment of head and neck squamous cell carcinoma. In comparison, laryngeal squamous cell carcinoma needs more aggressive treatment than well-differentiated thyroid carcinoma. The prevalence of thyroid papillary carcinoma, as an incidental finding in our study was 0.01%. Therefore, preoperative evaluation of the thyroid gland by ultrasonography and fine needle aspiration biopsy of suspicious lesions is recommended in patients who are candidates for open laryngectomy.

  14. Carcinoma Basocelular localmente invasor

    OpenAIRE

    Sofia Moreira-Silva; Margarida Carvalho

    2015-01-01

    O Carcinoma basocelular é uma neoplasia cutânea comum, de crescimento lento, com baixo potencial de metastização mas com alto potencial de invasão local agressiva e destruição de pele e tecido circundante como osso. Apresenta-se um homem de 79 anos com um carcinoma basocelular submetido a exérese cirúrgica, mas com posterior recidiva. Foi proposto para exérese alargada com plastia, mas recusou e abandonou seguimento em 2006. Em Maio 2011 é trazido ao serviço de urgência por crises convulsiv...

  15. Urachal Carcinoma: Imaging Findings

    Directory of Open Access Journals (Sweden)

    Vanessa Monteiro

    2012-02-01

    Full Text Available Urachal carcinoma is a rare neoplasm, which accounts for only 0.5–2% of bladder malignancies, and arises from a remnant of the fetal genitourinary tract. A 46-year-old woman presented with a history of pelvic pain and frequent daytime urination. Ultrasound (US, computed tomography (CT, and magnetic resonance (MR demonstrated a supravesical heterogeneous mass with calcifications. The patient underwent a partial cystectomy with en-bloc resection of the mass and histopathological examination revealed the diagnosis of urachal adenocarcinoma. Urachal carcinomas are usually associated with poor prognosis and early diagnosis is fundamental. CT and MR are useful to correctly diagnose and preoperatively staging.

  16. Gingival squamous cell carcinoma

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    Amit Walvekar

    2017-01-01

    Full Text Available Oral squamous cell carcinoma (OSCC is the most common epithelial malignancy affecting the oral cavity. The most common sites for the development are lateral surface of tongue and floor of mouth; the least common sites are soft palate, gingiva, and buccal mucosa. Gingival squamous cell carcinoma can mimic a multitude of oral lesions and enlargements, especially those of inflammatory origin. In addition, predisposing and presenting factors are different from those of other OSCCs. Careful examination as well as routine biopsy are crucial for accurate diagnosis.

  17. Wnt/β-Catenin Signaling Regulates the Expression of the Ammonium Permease Gene RHBG in Human Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Ahmad Merhi

    Full Text Available Ammonium is a metabolic waste product mainly d