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Colorectal Carcinoma (colorectal + carcinoma)
Kinds of Colorectal Carcinoma Terms modified by Colorectal Carcinoma Selected AbstractsMacroscopic Classificatrion of Early Colorectal Carcinoma: A Comparison Between Japan and ChinaDIGESTIVE ENDOSCOPY, Issue 4 2000Fang-yu Wang Background: To clarify the similarities and dissimilarities in the macroscopic classification criteria for early colorectal carcinoma (CRC) between Japan and China. Methods: Six early CRC cases were included in this study. Eleven Japanese and Chinese endoscopists were asked to review the colonoscopic pictures of these cases, including before and after indigocarmine spraying. After viewing the pictures, all the endoscopists individually made their classificatory diagnoses of these cases and indicated the findings on which they based each diagnosis. Results: Some lesions diagnosed by Japanese endoscopists as IIa or IIa + IIc, might be classified as Is or Isp by Chinese endoscopists. For superficial lesions consisting of elevation with central depression, IIa + depression, IIa + IIc or IIc + IIa were classified according to the ratio of elevated area/depressed area. However, international as well as interobserver differences still existed in the classification of such lesions. In addition, most Chinese endoscopists overlooked the slightly depressed part on the top of a protruded lesion. Conclusion: Discrepancies on macroscopic classification for early CRC do exist between Japanese and Chinese endoscopists, which were found not only in terminology, but also in recognition of some lesions. In order to develop a universal macroscopic classification, there is a great need for international communication and cooperation. [source] Pancreatitis-Associated Protein Is Related Closely to Neoplastic Proliferative Activity in Patients with Colorectal CarcinomaTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 2 2009Guang Cao Abstract Pancreatitis-associated protein (PAP) is a secretory protein that is not only expressed during acute pancreatitis but also in pancreatic adenocarcinoma, gastric carcinoma, hepatocellular carcinoma, and colorectal carcinoma. Expression in carcinoma might be another characteristic of PAP. The aim of our study was to assess, in 27 patients undergoing surgery for colorectal carcinoma, the expression of the PAP mRNA and to evaluate its association with DNA ploidy and proliferative activity (S-phase fraction, SPF) by reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometric analysis (FCM). PAP mRNA was expressed in 29.6% (8 of 27) of the patients with colorectal carcinoma. DNA aneuploid and high SPF were found in 87.5% (7 of 8) of patients with PAP mRNA positive colorectal carcinoma. The serum PAP level was significantly elevated in patients with colorectal carcinoma when compared with the healthy subjects. Twelve of the 27 patients with colorectal carcinoma had high serum PAP concentrations (>25 ng/mL) and the mean SPF was 17.82% ± 8.02%, which was significantly higher compared with the normal colorectal tissue group (7.33% ± 3.18%, P < 0.05). The mean serum PAP concentration of DNA aneuploidy colorectal carcinomas was 46.67 ± 17.58 ng/mL, which was significantly different when compared with the DNA diploidy group (19.18 ± 8.89 ng/mL, P < 0.05). PAP mRNA expression and serum PAP levels are closely related to neoplastic proliferative activity in patients with colorectal carcinoma. No significant differences are observed between PAP mRNA expression and clinicopathologic parameters (P > 0.05). Anat Rec, 2009. © 2008 Wiley-Liss, Inc. [source] Risk of Colorectal Carcinoma in Post-Liver Transplant Patients: A Systematic Review and Meta-analysisAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2010J. Sint Nicolaas Liver transplant patients (LTx) have an increased risk for developing de novo malignancies, but for colorectal cancer (CRC) this risk is less clear. We aimed to determine whether the CRC risk post-LTx was increased. A systematic search was performed in MEDLINE and Cochrane databases to identify studies published between 1986 and 2008 reporting on the risk of CRC post-LTx. The outcomes were (1) CRC incidence rate (IR per 100 000 person-years (PY)) compared to a weighted age-matched control population using SEER and (2) relative risk (RR) for CRC compared to the general population. If no RR data were available, the RR was estimated using SEER. Twenty-nine studies were included. The overall post-LTx IR was 119 (95% CI 88,161) per 100 000 PY. The overall RR was 2.6 (95% CI 1.7,4.1). The non-primary sclerosing cholangitis (PSC) IR was 129 per 100 000 PY (95% CI 81,207). Compared to SEER (71 per 100 000 PY), the non-PSC RR was 1.8 (95% CI 1.1,2.9). In conclusion, the overall transplants and the subgroup non-PSC transplants have an increased CRC risk compared to the general population. However, in contrast to PSC, non-PSC transplants do not need an intensified screening strategy compared to the general population until a prospective study further defines recommendations. [source] Improved prediction of recurrence after curative resection of colon carcinoma using tree-based risk stratificationCANCER, Issue 5 2004Martin Radespiel-Tröger M.D. Abstract BACKGROUND Patients who are at high risk of recurrence after undergoing curative (R0) resection for colon carcinoma may benefit most from adjuvant treatment and from intensive follow-up for early detection and treatment of recurrence. However, in light of new clinical evidence, there is a need for continuous improvement in the calculation of the risk of recurrence. METHODS Six hundred forty-one patients with R0-resected colon carcinoma who underwent surgery between January 1, 1984 and December 31, 1996 were recruited from the Erlangen Registry of Colorectal Carcinoma. The study end point was time until first locoregional or distant recurrence. The factors analyzed were: age, gender, site in colon, International Union Against Cancer (UICC) pathologic tumor classification (pT), UICC pathologic lymph node classification, histologic tumor type, malignancy grade, lymphatic invasion, venous invasion, number of examined lymph nodes, number of lymph node metastases, emergency presentation, intraoperative tumor cell spillage, surgeon, and time period. The resulting prognostic tree was evaluated by means of an independent sample using a measure of predictive accuracy based on the Brier score for censored data. Predictive accuracy was compared with several proposed stage groupings. RESULTS The prognostic tree contained the following variables: pT, the number of lymph node metastases, venous invasion, and emergency presentation. Predictive accuracy based on the validation sample was 0.230 (95% confidence interval [95% CI], 0.227,0.233) for the prognostic tree and 0.212 (95% CI, 0.209,0.215) for the UICC TNM sixth edition stage grouping. CONCLUSIONS The prognostic tree showed superior predictive accuracy when it was validated using an independent sample. It is interpreted easily and may be applied under clinical circumstances. Provided that their classification system can be validated successfully in other centers, the authors propose using the prognostic tree as a starting point for studies of adjuvant treatment and follow-up strategies. Cancer 2004;100:958,67. © 2004 American Cancer Society. [source] Colorectal carcinoma among Indigenous people: a public hospital-based study in Townsville and Cairns, North Queensland, AustraliaANZ JOURNAL OF SURGERY, Issue 11 2005Ping-Yan Lu Introduction: There are very little clinical and pathological data on colorectal cancer among Indigenous people in Australia. Methods: A retrospective study on Indigenous patients treated for colorectal cancer at the Townsville and Cairns Base Hospitals from 1999 to 2004 was carried out in order to better characterise this disease in the Indigenous population. Results: There were 25 patients (12 M, 13 F) with a median age of 57.3 years. The majority (56%) of the tumours were left-sided, being in the sigmoid colon, rectosigmoid junction and rectum. Of the patients, 60% had American Joint Committee on Cancer (AJCC) staging system Stage I and II disease at presentation. There was a relatively high proportion of poorly differentiated adenocarcinomas (40%). Six patients died of the disease. The median follow-up was 20.5 months (range 2,51). Conclusions: Comparisons were made with available data on colorectal cancer in the general Australian population. The limitations and deficiencies of the study, as well as problems of data collection on Indigenous people were discussed. [source] Colorectal carcinoma in young adults: a retrospective study on Indian patients: 2000,2008COLORECTAL DISEASE, Issue 10Online 2010S. Gupta Abstract Aim, To highlight an increased incidence of colorectal cancer (CRC) amongst young Indian adults. Method, A retrospective study of 305 cases of CRC admitted to SSKM Hospital, Kolkata, India during 2000,2008 was carried out. Results, The ratio (0.64) of under-40 to above-40 CRC patients reported in this study is comparable to those from premier Oncology Centers in India (,0.52) and is higher than those in the Indian National Cancer Registry (,0.20) and international average (0.07). Distinctive tumour characteristics in younger patients including left-sided lesion (69.7%), presentation at an advanced (III/IV) stage (60%), poor histological differentiation (50%) and predominance of mucin-secreting adenocarcinoma (80%) are similar to those reported in the international literature. Some features are suggestive of hereditary non polyposis colorectal cancer syndrome, which may be a possible reason for the high proportion of young CRC patients. Conclusion, A high index of suspicion for CRC among young Indian adults is necessary. [source] Enhanced expression of MMP-7 and MMP-13 in inflammatory bowel disease: A precancerous potential?INFLAMMATORY BOWEL DISEASES, Issue 11 2006Dr. Timo Rath PhD Abstract Matrix metalloproteinases (MMPs) are responsible for the turnover and degradation of extracellular matrix. They play a crucial role in the growth and migration of colorectal carcinoma cells. Colorectal carcinomas are characterized by enhanced expression of MMP-2, MMP-9, MMP-7, and MMP-13. The aim of this study was to determine the expression levels of MMP-2, MMP-9, MMP-7, MMP-13, and MMP-14 and their specific inhibitor TIMP-1 in inflammatory bowel diseases and precancerous lesions of the colon, i.e., Crohn's disease and ulcerative colitis, and in adenomatous polyps (APs) for comparison. Biopsy samples of pathological and healthy tissue were obtained from 40 patients with inflammatory bowel disease (ulcerative colitis, n = 17; Crohn's disease, n = 23) and from 19 patients with APs. mRNA was measured by quantitative real-time polymerase chain reaction to study MMP and TIMP-1 gene expression in both pathological and normal mucosal specimens. For MMP-2, MMP-9, and TIMP-1, protein expression also was quantified with sandwich enzyme-linked immunosorbent assay. In biopsy specimens of Crohn's disease and ulcerative colitis, significantly increased levels of MMP-2, MMP-7, and MMP-13 mRNA were found. MMP-2 and MMP-9 showed enhanced secretion on the protein level. AP revealed an increased transcription of MMP-7 and MMP-13 genes. MMP-14 mRNA was decreased in APs. MMPs, especially MMP-7 and MMP-13, which are expressed primarily on the tumor cell surface, are elevated in inflammatory bowel disease, which may have more chance to evolve into malignancy than normal tissue. In APs, increased expression of MMP-7 and MMP-13 may serve as an early indicator for colorectal carcinogenesis. [source] Relationship between histopathological features and type V pit pattern determined by magnifying videocolonoscopy in early colorectal carcinomaDIGESTIVE ENDOSCOPY, Issue 2 2005Shiro Oka Background: The aim of the present study was to clarify the relationship between the histopathological features and type V pit pattern of early colorectal carcinoma. Methods: We examined the relationship between the type V pit pattern subtypes, the depth of submucosal invasion and the degrees of desmoplastic reaction, residual pit density and destruction of the intervening membrane between pits on the tumor surface in 135 cases of early colorectal carcinoma. The examinations involved magnifying videoendoscopy with indigo carmine dye spraying and crystal violet staining. The pit patterns were classified as one of two grades (VI, VN), and VN was further divided into three subtypes (A, B and C). The data obtained were evaluated by ,2 test, with significance accepted at < 0.05% for each analysis. Results: There were 64 VI, 24 VN -A, 28 VN -B and 19 VN -C lesions. The incidence of massive submucosal invasion (sm2, sm3) was significantly higher in VN -B and VN -C lesions than in VI and VN -A lesions (P < 0.05). Among VN pit pattern lesions, depth of submucosal invasion of VN -B and VN -C lesions was significantly greater than that of VN -A lesions (P < 0.01). The incidence of severe desmoplastic reaction in VN -B and VN -C lesions was significantly greater than that in VI lesions (P < 0.01). The incidence of severe desmoplastic reaction in VN -C lesions was significantly greater than that in VN -A lesions (P < 0.05). The incidence of low residual pit density in VN -C lesions was significantly greater than that in all other type V lesions. The incidence of mild to moderate and severe destruction of the intervening membrane between pits in VN lesions was significantly higher than that in VI lesions. Conclusions: Type V pit pattern subclassification is useful for predicting the depth of submucosal invasion in early colorectal carcinomas. The type V pit pattern subtypes are related to the degrees of desmoplastic reaction, the residual pit density and destruction of the intervening membrane between pits on the tumor surface. [source] Diagnosis of invasion depth in early colorectal carcinoma by pit pattern analysis with magnifying endoscopyDIGESTIVE ENDOSCOPY, Issue 2001Shinji Tanaka Background: The aim of this study was to clarify whether various pit patterns on the surface of colorectal tumors are associated with various levels of submucosal invasion. Methods: We examined pathologic features of the pit pattern of the tumor surface in 457 colorectal adenomas and early carcinomas. The examinations involved the use of magnifying endoscopy with indigocarmine dye spraying or crystal violet staining methods. Regarding the pit pattern classification, we used the types I, II, IIIL, IIIS, IV, VA and VN. We subclassified the VN pit pattern according to the area of the tumor surface covered into grades A (small), B (medium) and C (large). Results: Magnifying colonoscopic observation revealed the rates of submucosal invasion associated with specific pit patterns to be 1% (3/213) for IIIL, 5% (2/42) for IIIS, 8% (4/57) for IV, 14% (13/93) for VA and 80% (42/52) for VN. The rates of submucosal massive invasion (> 400 ,m) associated with specific pit patterns was 0% (0/213) for IIIL, 0% (0/42) for IIIS, 4% (2/57) for IV, 5% (5/93) for VA and 72% (38/52) for VN. Within the VN pit pattern subclassification, the incidence of submucosal invasion , 1500 ,m was found each grade (A, B & C): 5% (1/19) for grade A, 64% (14/22) for grade B and 93% (13/14) for grade C. Conclusion: Determination of pit pattern is useful for prediction of submucosal invasion depth and for decisions concerning treatment in colorectal tumors. Lesions with VA and non-grade C VN pit patterns are candidates for total endoscopic resection. A grade C VN pit pattern is a definite indicator of severely invasive submucosal carcinoma, which is unresectable by endoscopic resection. [source] Macroscopic Classificatrion of Early Colorectal Carcinoma: A Comparison Between Japan and ChinaDIGESTIVE ENDOSCOPY, Issue 4 2000Fang-yu Wang Background: To clarify the similarities and dissimilarities in the macroscopic classification criteria for early colorectal carcinoma (CRC) between Japan and China. Methods: Six early CRC cases were included in this study. Eleven Japanese and Chinese endoscopists were asked to review the colonoscopic pictures of these cases, including before and after indigocarmine spraying. After viewing the pictures, all the endoscopists individually made their classificatory diagnoses of these cases and indicated the findings on which they based each diagnosis. Results: Some lesions diagnosed by Japanese endoscopists as IIa or IIa + IIc, might be classified as Is or Isp by Chinese endoscopists. For superficial lesions consisting of elevation with central depression, IIa + depression, IIa + IIc or IIc + IIa were classified according to the ratio of elevated area/depressed area. However, international as well as interobserver differences still existed in the classification of such lesions. In addition, most Chinese endoscopists overlooked the slightly depressed part on the top of a protruded lesion. Conclusion: Discrepancies on macroscopic classification for early CRC do exist between Japanese and Chinese endoscopists, which were found not only in terminology, but also in recognition of some lesions. In order to develop a universal macroscopic classification, there is a great need for international communication and cooperation. [source] Helicobacter pylori Infection and Colorectal Cancer Risk: A Meta-AnalysisHELICOBACTER, Issue 2 2006Natalia Zumkeller Abstract Background:, Several studies suggested an association between Helicobacter pylori infection and colorectal carcinoma or adenoma risk. However, different authors reported quite varying estimates. We carried out a systematic review and meta-analysis of published studies investigating this association and paid special attention to the possibility of publication bias and sources of heterogeneity between studies. Materials and Methods:, An extensive literature search and cross-referencing were performed to identify all published studies. Summary estimates were obtained using random-effects models. The presence of possible publication bias was assessed using different statistical approaches. Results:, In a meta-analysis of the 11 identified human studies, published between 1991 and 2002, a summary odds ratio of 1.4 (95% CI, 1.1,1.8) was estimated for the association between H. pylori infection and colorectal cancer risk. The graphical funnel plot appeared asymmetrical, but the formal statistical evaluations did not provide strong evidence of publication bias. The proportion of variation of study results because of heterogeneity was small (36.5%). Conclusions:, The results of our meta-analysis are consistent with a possible small increase in risk of colorectal cancer because of H. pylori infection. However, the possibility of some publication bias cannot be ruled out, although it could not be statistically confirmed. Larger, better designed and better controlled studies are needed to clarify the situation. [source] c-FLIP expression in colorectal carcinomas: association with Fas/FasL expression and prognostic implicationsHISTOPATHOLOGY, Issue 2 2007P Korkolopoulou Aims:, Disruption of apoptotic cell death has been implicated in tumour aggressiveness in colonic carcinogenesis. The Fas,Fas ligand (FasL) system is involved in the execution of apoptosis induced by the immune system. c-FLIP protein constitutes an inhibitor of Fas and other (TRAIL) death receptor-mediated apoptosis. The aim of this study was to investigate the simultaneous expression of Fas, FasL and c-FLIP in relation to standard clinicopathological parameters and patients' outcome in colorectal cancer. Methods and results:, Levels of Fas, FasL and c-FLIP protein expression were quantified immunohistochemically in paraffin-embedded tissues from 90 patients. Immunopositivity was detected for Fas, FasL and c-FLIP in 71%, 35.5% and 68.8% of cases, respectively. Concurrent expression of Fas/FasL was seen in 28 samples (31%), of which 24 (85.7%) also displayed c-FLIP positivity (P = 0.04). c-FLIP overexpression (> 10%) tended to prevail marginally in higher stage tumours (P = 0.09). Additionally, FasL and c-FLIP adversely affected survival on both univariate (P = 0.001 and P = 0.0024, respectively) and multivariate analysis [hazard ratio (HR) 3.491, P = 0.005 and HR 2.960, P = 0.036, respectively]. Conclusions:, The frequent expression and coexpression of Fas, FasL and c-FLIP in colorectal carcinoma implicates c-FLIP as an inhibitor of the Fas,FasL-induced death pathway in these tumours. Moreover, c-FLIP conveys independent prognostic information in the presence of classical prognosticators. [source] Drug-eluting bead therapy in primary and metastatic disease of the liverHPB, Issue 7 2009Stewart Carter Abstract Background:, Drug-eluting bead transarterial chemoembolization (DEB-TACE) is a novel therapy for the treatment of hypervascuarized tumours. Through the intra-arterial delivery of microspheres, DEB-TACE allows for embolization as well as local release of chemotherapy in the treatment of hepatic malignancy, providing an alternative therapeutic option in unresectable tumours. Its role as an adjunct to surgical resection or radiofrequency ablation (RFA) is less clear. The purpose of this review is to summarize recent studies investigating DEB-TACE in order to better define safety, efficacy and outcomes associated with its use. Methods:, A systematic review of all published articles and trials identified nine clinical trials and 23 abstracts. These were reviewed for tumour histology, stage of treatment, delivery technique, outcome at follow-up, complications and mortality rates. Results:, Publications involved treatment of hepatocellular carcinoma (HCC), metastatic colorectal carcinoma (MCRC), metastatic neuroendocrine (MNE) disease and cholangiocarcinoma (CCA). Using Response Evaluation Criteria in Solid Tumours (RECIST) or European Association for the Study of the Liver (EASL) criteria, studies treating HCC reported complete response (CR) rates of 5% (5/101) at 1 month, 9% (8/91) at 4 months, 14% (19/138) at 6 months and 25% (2/8) at 10 months. Partial response (PR) was reported as 58% (76/131) at 1 month, 50% (67/119) at 4 months, 57% (62/108) at 6,7 months and 63% (5/8) at 10 months. Studies involving MCRC, CCA and MNE disease were less valuable in terms of response rate because there is a lack of comparative data. The most common procedure-associated complications included fever (46,72%), nausea and vomiting (42,47%), abdominal pain (44,80%) and liver abscess (2,3%). Rather than reporting individual symptoms, two studies reported rates of post-embolic syndrome (PES), consisting of fever, abdominal pain, and nausea and vomiting, at 82% (75/91). Six of eight studies reported length of hospital stay, which averaged 2.3 days per procedure. Mortality was reported as occurring in 10 of 456 (2%) procedures, or 10 of 214 (5%) patients. Conclusions:, Drug-eluting bead TACE is becoming more widely utilized in primary and liver-dominant metastatic disease of the liver. Outcomes of success must be expanded beyond response rates because these are not a reliable surrogate for progression-free survival or overall survival. Ongoing clinical trials will further clarify the optimal timing and strategy of this technology. [source] Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancerINTERNATIONAL JOURNAL OF CANCER, Issue 1 2010Zhaohui Huang Abstract MicroRNA (miRNA) opens up a new field for molecular diagnosis of cancer. However, the role of circulating miRNAs in plasma/serum in cancer diagnosis is not clear. The aim of this study was to investigate whether plasma miRNAs can be used as biomarkers for the early detection of colorectal carcinoma (CRC). We measured the levels of 12 miRNAs (miR-134, ,146a, ,17-3p, ,181d, ,191, ,221, ,222, ,223, ,25, ,29a, ,320a and ,92a) in plasma samples from patients with advanced colorectal neoplasia (carcinomas and advanced adenomas) and healthy controls using real-time RT-PCR. We found that plasma miR-29a and miR-92a have significant diagnostic value for advanced neoplasia. MiR-29a yielded an AUC (the areas under the ROC curve) of 0.844 and miR-92a yielded an AUC of 0.838 in discriminating CRC from controls. More importantly, these 2 miRNAs also could discriminate advanced adenomas from controls and yielded an AUC of 0.769 for miR-29a and 0.749 for miR-92a. Combined ROC analyses using these 2 miRNAs revealed an elevated AUC of 0.883 with 83.0% sensitivity and 84.7% specificity in discriminating CRC, and AUC of 0.773 with 73.0% sensitivity and 79.7% specificity in discriminating advanced adenomas. Collectively, these data suggest that plasma miR-29a and miR-92a have strong potential as novel noninvasive biomarkers for early detection of CRC. [source] Diagnostic value of FDG-PET in recurrent colorectal carcinoma: A meta-analysisINTERNATIONAL JOURNAL OF CANCER, Issue 1 2009Chenpeng Zhang Abstract Accurate detection of recurrent colorectal carcinoma remains a diagnostic challenge. The purposes of this study were to evaluate the diagnostic value of Positron emission tomography (PET) using fluor-18-deoxyglucose (FDG) in recurrent colorectal carcinoma with a meta-analysis. All the published studies in English relating the diagnostic value of FDG-PET in the detection of recurrent colorectal carcinoma were collected. Methodological quality of the included studies was evaluated. Pooled sensitivity, specificity and diagnostic odds ratio and SROC (summary receiver operating characteristic curves) were obtained by the statistical software. Twenty-seven studies were included in the meta-analysis. The pooled sensitivity and specificity for FDG-PET detecting distant metastasis or whole body involvement in recurrent colorectal carcinoma were 0.91 (95% CI 0.88,0.92) and 0.83 (95% CI 0.79,0.87), respectively. The pooled sensitivity and specificity for FDG-PET detecting hepatic metastasis were 0.97 (95% CI 0.95,0.98) and 0.98 (95% CI 0.97,0.99). The pooled sensitivity and specificity for pelvic metastasis or local regional recurrence were 0.94 (95% CI 0.91,0.97) and 0.94 (95% CI 0.92,0.96). FDG-PET is valuable for the assessment of recurrent colorectal carcinoma. © 2008 Wiley-Liss, Inc. [source] Expression and enzyme activity of ,(1,6)fucosyltransferase in human colorectal cancerINTERNATIONAL JOURNAL OF CANCER, Issue 3 2008Laura Muinelo-Romay Abstract Changes in enzyme activity and the expression levels of ,(1,6)fucosyltransferase [,(1,6)FT] have been reported in certain types of malignant transformations. To develop a better understanding of the role of ,(1,6)FT in human colorectal carcinoma (CRC), we analysed the enzyme activity in healthy and tumour tissues. ,(1,6)FT activity was considerably higher in tumour tissue than in healthy tissue and was related to gender, lymph node metastasis, type of growth and tumour stage. We also observed a significant increase in the ,(1,6)FT expression in tumour tissues as compared to healthy and transitional tissues, inflammatory lesions and adenomas. The immunohistochemical expression in tumour tissues was correlated with the degree of infiltration through the intestinal wall. Finally, a statistical correlation was found between enzyme activity and expression obtained by Western blot in colorectal tumours when compared in the same patient. All these findings demonstrate an alteration of ,(1,6)FT activity and expression in CRC. © 2008 Wiley-Liss, Inc. [source] Linear relationship between Wnt activity levels and apoptosis in colorectal carcinoma cells exposed to butyrateINTERNATIONAL JOURNAL OF CANCER, Issue 4 2004Darina L. Lazarova Abstract We have reported that butyrate, a fatty acid produced by dietary fiber that induces cell cycle arrest, differentiation and/or apoptosis in colorectal carcinoma (CRC) cells in vitro, modulates Wnt activity in 2 CRC cell lines (Bordonaro et al., Int. J. Cancer, 2002; 97:42,51). Our study determines how changes in the levels of Wnt activity induced by butyrate relate to the effects of butyrate on apoptosis, cell cycle arrest and differentiation of CRC cells. In 10 human CRC cell lines a direct relationship was shown between apoptosis and butyrate-induced increase in Wnt activity, as well as between suppressed clonal growth and increased Wnt activity. No correlation existed between butyrate-induced increase in Wnt activity and differentiation. The direct relationship between apoptosis and Wnt activity was supported by analyses of DLD-1 and HCT-116 cells expressing a dominant negative form of Tcf4, and therefore, with repressed Wnt activity, as well as by measuring the ratio of apoptotic to live cells in flow cytometry-sorted cell fractions with high and low Wnt activity. Novel flow cytometric methodology was utilized to show that butyrate differentially increases the number of cells with Wnt activity in different CRC cell lines. Thus, CRC cell lines in which butyrate upregulated Wnt activity to relatively high levels were most susceptible to the apoptotic effects of butyrate, whereas cell lines in which butyrate modestly modulated Wnt activity were less affected. © 2004 Wiley-Liss, Inc. [source] Prognostic value of serum angiogenic activity in colorectal cancer patientsJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 1 2007Francisco-Jesus Gonzalez Abstract Angiogenesis, resulting from an imbalance between angiogenic activator factors and inhibitors, is required for tumour growth and metastasis. The determination of the circulating concentration of all angiogenic factors (activators and inhibitors) is not feasible at present. We have evaluated diagnostic and prognostic values of the measurement of serum angiogenic activity in colorectal carcinoma (CRC) patients. Serum proliferative activity (PA) on human umbilical vein endothelial cells (HUVEC) in vitro, and serum vascular endothelial growth factor (VEGF) levels were determined by ELISA in 53 patients with primary CRC, 16 subjects with non-neoplastic gastrointestinal disease (SC) and 34 healthy individuals. Data were compared with clinical outcome of the patients. Although serum from CRC patients significantly increased the PA of HUVEC, compared to culture control (HUVEC in medium + 10% foetal bovine serum (FBS); P < 0.001); our results indicate that serum PA in CRC patients was similar to that of SC or healthy individuals. There was no correlation between serum PA and circulating VEGF concentrations. Surgery produced a decrease of PA at 8 hrs after tumour resection in CRC patients compared to pre-surgery values (186 ± 47 versus 213 ± 41, P < 0.001). However, an increase in serum VEGF values was observed after surgery (280 [176,450] versus 251 [160,357] pg/ml, P = 0.004). Patients with lower PA values after surgery showed a worse outcome that those with higher PA values. Therefore, this study does not support a diagnostic value for serum angiogenic activity measured by proliferative activity on HUVEC but suggests it could have a prognostic value in CRC patients. [source] A case report of inflammatory nonscarring alopecia associated with the epidermal growth factor receptor inhibitor erlotinibJOURNAL OF CUTANEOUS PATHOLOGY, Issue 12 2009Marinya Pongpudpunth Epidermal growth factor receptor inhibitors (EGFRIs) are new anticancer agents that act by inhibiting EGFR signaling transduction pathways, thus decreasing tumor growth. In more than 30 countries, EGFRIs are currently used in the treatment of a number of solid tumors, and other indications are being sought. In the United States, select EGFRIs have been approved in certain patients with non-small cell lung cancer, metastatic colorectal carcinoma, and advanced squamous cell carcinoma of the head and neck. Various cutaneous side effects of EGFRIs have been reported, including acneiform eruptions, chronic paronychia, xerosis, a seborrheic dermatitis-like eruption, changes in hair texture, and nonscarring alopecia. We present a 60-year-old woman with non-small cell lung cancer who developed a persistent generalized itchy eruption and progressive nonscarring alopecia shortly after initiation of erlotinib (Tarceva). Scalp biopsy showed near-equal number of anagen and catagen/telogen hair follicles, and a superficial and deep perivascular lymphoplasmocytic infiltration. These changes are typical of the nonscarring alopecia induced by EGFRIs. Because it is likely that EGFRIs will be increasingly used, dermatopathologists are likely to see more reactions from these agents. Familiarity with their side effects is essential to accurate diagnosis and effective patient management. [source] Flat adenoma in colon: Two decades of debateJOURNAL OF DIGESTIVE DISEASES, Issue 4 2010Patrick CP LAU The existence of flat adenomas in the colon is well recognized. Whether they represent a distinct disease with a pathogenetic pathway different from that of the classical adenoma-carcinoma sequence in colorectal tumorigenesis and have higher malignant potential remains a matter of debate. To review the epidemiology, clinical features, detection and management of flat and depressed (non-polypoid) colonic neoplasm, we performed a thorough literature review on studies focusing on the prevalence, histological features, genetics, detection and treatment of flat and depressed (non-polypoid) colonic neoplasm. A high percentage of severe dysplasia in flat colonic adenomas has not been consistently demonstrated. Their malignant potential appears to be size-dependent. Flat adenomas are found to have a lower incidence of major genetic abnormalities involved in the classical adenoma-carcinoma sequence and that has raised suspicions that they may have a different pathogenesis. The depressed type of colorectal carcinoma is uncommon but shows more aggressive behavior. More advanced colonoscopic techniques, such as chromoendoscopy, may enhance the detection of small and inconspicuous colonic neoplastic lesions that lack a protruding configuration. It is essential for endoscopists to appreciate the existence and clinical significance of flat and depressed colonic lesions as an important variant of colonic neoplasms so that the goal of reducing colorectal carcinoma incidence by polypectomy can be better achieved. [source] Multiple primary malignancies in Spanish patients with hepatocellular carcinoma: Analysis of a hospital-based tumor registryJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 8 2009Mario Fernández-Ruiz Abstract Background and Aim:, Little is known about the etiological associations and clinical features of extrahepatic primary malignant (EHPM) neoplasms in subjects with hepatocellular carcinoma (HCC). The aim of this study was to characterize this phenomenon in a consecutive series of Spanish patients in order to define its natural history and influence on survival. Methods:, A retrospective analysis of 245 patients with HCC during the period 1999,2003 was performed. Subjects identified with a second primary malignancy elsewhere constituted the EHPM group and were compared to patients with HCC alone. Results:, Eighteen patients (7.3%) had one or two associated extrahepatic malignancies (mean age 67.7 ± 9.7 years); of these, 17 had double cancer and one patient, triple. Nine of the 19 EHPM occurred before HCC diagnosis. The associated cancers included five cases of colorectal carcinoma, four cases of head and neck carcinoma, three cases of genitourinary cancer, two cases of lymphoproliferative disorder, one lung carcinoma, one skin melanoma, one breast carcinoma, and two cancers of unknown origin. Age and sex distribution, etiology of underlying hepatopathy, and liver function tests did not differ significantly between both groups. There was no difference between the overall survival rates. Conclusions:, EHPM is not rare among Spanish patients with HCC, although no specific clinicopathological features were detected in this population. Our results suggest that the association of another primary tumor with HCC does not imply a worse prognosis. The possibility of development of EHPM should be kept in mind when deciding on therapy and follow-up of HCC. [source] MR colonography for the assessment of colonic anastomosesJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 1 2006Waleed Ajaj MD Abstract Purpose To assess colonic anastomoses in patients after surgical treatment by means of MR colonography (MRC) in comparison with conventional colonoscopy (CC). Materials and Methods A total of 39 patients who had previously undergone colonic resection and end-to-end-anastomosis were included in the study. MRI was based on a dark-lumen approach. Contrast-enhanced T1-weighted (T1w) three-dimensional (3D) images were collected following the rectal administration of water for colonic distension. The MRC data were evaluated by two radiologists. The criteria employed to evaluate the anastomoses included bowel wall thickening and increased contrast uptake in this region. Furthermore, all other colonic segments were assessed for the presence of pathologies. Results In 23 and 20 patients the anastomosis was rated to be normal by MRC and CC, respectively. In three patients CC revealed a slight inflammation of the anastomosis that was missed by MRI. A moderate stenosis of the anastomosis without inflammation was detected by MRC in five patients, which was confirmed by CC. In the remaining 11 patients a relevant pathology of the anastomosis was diagnosed by both MRC and CC. Recurrent tumor was diagnosed in two patients with a history of colorectal carcinoma. In the other nine patients inflammation of the anastomosis was seen in seven with Crohn's disease (CD) and two with ulcerative colitis. MRC did not yield any false-positive findings, resulting in an overall sensitivity/specificity for the assessment of the anastomosis of 84%/100%. Conclusion MRC represents a promising alternative to CC for the assessment of colonic anastomoses in patients with previous colonic resection. J. Magn. Reson. Imaging 2006. © 2006 Wiley-Liss, Inc. [source] Hepatic arterial infusion of floxuridine and dexamethasone plus high-dose Mitomycin C for patients with unresectable hepatic metastases from colorectal carcinomaJOURNAL OF SURGICAL ONCOLOGY, Issue 2 2005Nancy Kemeny MD Abstract Background In vitro data suggest increased cytotoxicity with Mitomycin C (Mit-C) and Floxuridine (FUDR). Based on these data, we performed a phase II trial of hepatic arterial infusion (HAI) of FUDR and Dexamethasone (Dex) plus high-dose Mit-C for patients with unresectable hepatic metastases from colorectal carcinoma. Methods High-dose Mit-C (15 mg/m2) was added via the pump sideport to HAI FUDR and Dex for 14 days of a 28-day cycle. Mit-C was given on days 1 and 29, and FUDR was given indefinitely until disease progression or discontinuation of therapy due to toxicity. Results Sixty-three patients with unresectable liver metastases were entered. The chemotherapy-naďve group (n,=,26) and those previously treated (n,=,37) had similar response and median survival: 73% and 70%, and 23 and 20 months, respectively. The major toxicities were liver bilomas (7.9%), elevation in bilirubin level >3 (22%), and biliary sclerosis (9.5%). Hematologic and gastrointestinal toxicity was less than 2%. Conclusion The addition of high-dose Mit-C to HAI FUDR and Dex produced a high response rate even in previously treated patients. The median survival was 21 months even though half the patients were previously treated with chemotherapy. Biliary toxicity was higher than expected; therefore, alternatives to high dose Mit-C should be investigated when exploring additions to HAI therapy with FUDR and Dex. J. Surg. Oncol. 2005;91:97,101. © 2005 Wiley-Liss, Inc. [source] CC531s colon carcinoma cells induce apoptosis in rat hepatic endothelial cells by the Fas/FasL-mediated pathwayLIVER INTERNATIONAL, Issue 4 2003Katrien Vekemans Abstract The mechanisms involved in colorectal carcinoma with liver metastasis are not well known. Metastasizing colon carcinoma cells express more FasL than primary colon carcinoma cells and cancer cells induce apoptosis in hepatocytes by the Fas/FasL pathway. Therefore, this study focused on Fas/FasL expression and functionality in rat liver sinusoidal endothelial cells (LSECs) and CC531s colon carcinoma cells in vitro and in vivo. RT-PCR and immunochemistry revealed Fas and FasL in LSECs and CC531s, respectively. Functionality of Fas was assessed in vitro by incubation with human recombinant FasL (1,100 ng/ml) with or without enhancer. At concentrations of 10 and 100 ng/ml with enhancer, respectively 21% and 44% of endothelial cells showed signs of apoptosis using Hoechst 33342/propidium iodide staining and electron microscopy. In co-cultures, apoptosis could be detected in endothelial cells neighboring the CC531s and could be inhibited by an antagonistic FasL antibody. Moreover, 18 h after mesenteric injection of CC531s, the sinusoidal endothelium revealed disruption. In conclusion, (i) CC531s cells induce apoptosis in LSECs in vitro by using Fas/FasL; (ii) CC531s cells damage the sinusoidal endothelial lining in vivo; and (iii) this might provide FasL-positive tumor cells a gateway towards the hepatocytes. [source] Association between activation of atypical NF-,B1 p105 signaling pathway and nuclear ,-catenin accumulation in colorectal carcinomaMOLECULAR CARCINOGENESIS, Issue 2 2010Johannes C. Lauscher Abstract Recent studies have demonstrated that increased expression of coding region determinant-binding protein (CRD-BP) in response to ,-catenin signaling leads to the stabilization of ,-TrCP1, a substrate-specific component of SCF E3 ubiquitin ligase complex, resulting in an accelerated degradation of I,B, and activation of canonical nuclear factor-,B (NF-,B) pathway. Here, we show that the noncanonical NF-,B1 p105 pathway is constitutively activated in colorectal carcinoma specimens, being particularly associated with ,-catenin-mediated increased expression of CRD-BP and ,-TrCP1. In the carcinoma tissues exhibiting high levels of nuclear ,-catenin the phospho-p105 levels were increased and total p105 amounts were decreased in comparison to that of normal tissue indicating an activation of this NF-,B pathway. Knockdown of CRD-BP in colorectal cancer cell line SW620 resulted in significantly higher basal levels of both NF-,B inhibitory proteins, p105 and I,B,. Furthermore decreased NF-,B binding activity was observed in CRD-BP siRNA-transfected SW620 cells as compared with those transfected with control siRNA. Altogether, our findings suggest that activation of NF-,B1 p105 signaling in colorectal carcinoma might be attributed to ,-catenin-mediated induction of CRD-BP and ,-TrCP1. © 2009 Wiley-Liss, Inc. [source] Colorectal carcinoma development in inducible nitric oxide synthase-deficient mice with dextran sulfate sodium-induced ulcerative colitisMOLECULAR CARCINOGENESIS, Issue 5 2007Darren N. Seril Abstract The overproduction of reactive oxygen and nitrogen species (RONS) may play an important role in ulcerative colitis (UC)-associated carcinogenesis. In order to study the role of nitric oxide (NO) in UC-associated colorectal carcinogenesis, the development of colorectal carcinoma was studied using the DSS-induced and iron-enhanced model of chronic UC in inducible nitric oxide synthase (iNOS)-deficient mice. Female wild-type C57BL/6 (iNOS+/+) and iNOS,/, mice were administered 1% DSS (w/v) through the drinking fluid for 15 DSS cycles and fed twofold iron-enriched diet. Colorectal inflammation and mucosal ulceration of moderate severity were observed in both iNOS+/+ and iNOS,/, mice. Similar tumor incidence and multiplicity in the colon were observed that 15 out of 23 (65.2%) iNOS+/+ mice developed colorectal tumors with a tumor multiplicity of 1.47,±,0.17 (mean,±,SE) after 15 DSS cycles, and 13 out of 19 (68.4%) iNOS,/, mice developed colorectal tumors with a tumor multiplicity of 2.08,±,0.21. Histopathologically, the tumors were confirmed to be well-differentiated adenocarcinomas. Nitrotyrosine, an indicator of peroxynitrite-caused protein modification, was detectable by immunohistochemistry in inflammatory cells and epithelial cells of the colon in iNOS+/+ and iNOS,/, mice, and no difference in staining intensity was observed between the two groups. Immunostaining for endothelial NOS (eNOS) was observed in lamina propria macrophages and colonic blood vessels, and eNOS protein levels were increased in the inflamed colon. These results show that there is no difference in UC-associated cancer development in iNOS+/+ and iNOS,/, mice, and suggest that in the absence of iNOS, other factors, such as eNOS, may play a role in nitrosative stress and UC-associated carcinogenesis in this model system. © 2006 Wiley-Liss, Inc. [source] Oral and maxillofacial manifestations of familial adenomatous polyposisORAL DISEASES, Issue 4 2007MA Wijn Patients with familial adenomatous polyposis (FAP) develop multiple premalignant colorectal adenomas. Untreated, one or more of these polyps will progress to colorectal carcinoma in middle-aged adults. Extra-intestinal manifestations of FAP are frequently observed and this combination has been called Gardner's syndrome. Oral and maxillofacial symptoms of FAP include an increased risk of jaw osteomas, odontomas and supernumerary or unerupted teeth. Early diagnosis of FAP is crucial and may be life saving. As oral signs usually precede gastrointestinal symptoms, the dentist may play an important role in the diagnosis of FAP. [source] Apoptosis as an independent prognostic indicator in squamous cell carcinoma of the esophagusPATHOLOGY INTERNATIONAL, Issue 7 2001Hiroshi Shibata Apoptosis plays a crucial role in determining net cell proliferation and cell turnover in various tumors. The rate of apoptosis in tumor cells has been reported to be a useful prognostic indicator in colorectal carcinoma. We examined apoptosis in 72 specimens of esophageal squamous cell carcinoma, by the terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) digoxigenin,nick end labeling (TUNEL) method. We examined correlation of apoptosis with outcome, clinicopathological features, and expression of the apoptosis-related proteins p53 and Bcl-2. The percentage of apoptotic cells, or apoptotic index (AI), ranged from 0.8 to 9.4 (mean: 3.47; SD: 2.02). Overall, 5-year survival of patients with high AI (AI , 5.0; n= 18) tumors was significantly higher than that of patients with low AI tumors (AI < 5.0; n= 58; 76.9% versus 44.9%; P= 0.042). AI did not correlate significantly with the clinicopathological features of patient age and sex, depth of tumor and histological differentiation, lymph node metastasis, lymphatic invasion, or venous invasion. In p53-negative tumors, the AI was significantly higher than in p53-positive tumors. We concluded that AI may be a useful prognostic indicator in esophageal squamous cell carcinoma following curative surgery, and that apoptosis in this tumor is related to relative underexpression of p53 protein. [source] Photochemical Internalization of Transgenes Controlled by the Heat-shock Protein 70 PromoterPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 3 2006Lina Prasmickaite ABSTRACT Photochemical internalization (PCI) is a targeting technique that facilitates endosomal escape of macromolecules, such as transgenes, in response to photochemical treatment with endosome/lysosome-localized photosensitizers, such as disul-fonated meso-tetraphenylporphine (TPPS2a). In gene therapy this leads to enhanced transgene expression. Moreover, photochemical treatment generally activates transcription of stress-response genes, such as heat-shock proteins (HSPs), via stimulation of corresponding promoters. Therefore, we used HSP70 (HSPp; a promoter from the HSP family gene) and investigated whether the PCI stimulus could also activate HSPp and thereby stimulate transcription (expression) of the HSPp-controlled transgene internalized via PCI. Using human colorectal carcinoma and hepatoma cell lines in vitro, we showed that TPPS2a -based photochemical treatment enhances expression of cellular HSP70, which correlated with a photo-chemically enhanced expression (approximately 2-fold, at PCI-optimal doses) of the HSPp-controlled transgene integrated in the genome. Furthermore, PCI enhanced expression of the HSPp-controlled episomal transgene delivered as a plas-mid. However, in plasmid-based transfection, PCI-mediated enhancement with HSPp did not exceed the enhancement achieved with the constitutive active CMV promoter. In conclusion, we demonstrated that the PCI-relevant treatment initiates HSP70 response and that the HSP70 promoter can be used in combination with PCI, leading to PCI-enhanced expression of the HSPp-controlled transgene. [source] An application of the 2-nitrobenzenesulfenyl method to proteomic profiling of human colorectal carcinoma: A novel approach for biomarker discoveryPROTEOMICS - CLINICAL APPLICATIONS, Issue 6 2008Makoto Watanabe Abstract In the development of novel biomarkers, the proteomic approach is advantageous because using it the cancer-associated proteins can be directly identified. We previously developed a 2-nitrobenzenesulfenyl (NBS) method to improve quantitative proteome analysis. Here, we applied this method to proteomic profiling of colorectal carcinoma (CRC) to identify novel proteins with altered expression in CRC. Each pair of tumor and normal tissue specimens from 12 CRC patients was analyzed, and approximately 5000 NBS-labeled paired peaks were quantified. Peaks with altered signal intensities (>1.5-fold) and occurring frequently in the samples (>70%) were selected, and 128 proteins were identified by MS/MS analyses as differentially expressed proteins in CRC tissues. Many proteins were newly revealed to be CRC related; 30 were reported in earlier studies of CRC. Six proteins that were up-regulated in CRC (ZYX, RAN, RCN1, AHCY, LGALS1, and VIM) were further characterized and validated by Western blot and immunohistochemistry. All six were found to be CRC-localized, either in cancer cells or in stroma cells near the cancer cells. These results indicate that the proteins identified in this study are novel candidates for CRC markers, and that the NBS method is useful in proteome mining to discover novel biomarkers. [source] | ||||||||||||||||||||||||||||||||||