Colon Carcinoma (colon + carcinoma)

Distribution by Scientific Domains

Kinds of Colon Carcinoma

  • human colon carcinoma

  • Terms modified by Colon Carcinoma

  • colon carcinoma cell
  • colon carcinoma cell line

  • Selected Abstracts

    Colon Carcinoma- Bugs, Bacterium and Bone Marrow

    COLORECTAL DISEASE, Issue 3 2010
    Marc Winslet
    No abstract is available for this article. [source]

    Colon carcinoma in African children

    PEDIATRIC BLOOD & CANCER, Issue 6 2003
    David K. Stones MBChB (UCT), MMED (Paed)
    No abstract is available for this article. [source]

    Regulation of E-cadherin and ,-catenin by Ca2+ in colon carcinoma is dependent on calcium-sensing receptor expression and function

    Narasimharao Bhagavathula
    Abstract An siRNA directed against the extracellular calcium-sensing receptor (CaSR) was used to down-regulate this protein in CBS colon carcinoma cells. In additional studies, we utilized a variant of the parental CBS line that demonstrates CaSR expression but does not upregulate this protein in response to extracellular Ca2+. In neither the siRNA-transfected cells nor the Ca2+ -nonresponsive variant cells did inclusion of Ca2+ in the culture medium inhibit proliferation or induce morphological alterations. Extracellular Ca2+ also failed to induce E-cadherin production or a shift in ,-catenin from the cytoplasm to the cell membrane. In mock-transfected cells and in a Ca2+ -responsive variant line derived from the same parental CBS cells, Ca2+ treatment resulted in growth-reduction. This was accompanied by increased E-cadherin production and a shift in ,-catenin distribution from the cytoplasm to the cell membrane. Additionally, down-regulation of c-myc and cyclin D1 expression was observed in mock-transfected cells and in the Ca2+ -responsive variant line (along with reduced T cell factor transcriptional activation). Neither c-myc nor cyclin D1 was significantly down-regulated in the siRNA-transfected cells or in the Ca2+ -nonresponsive variant cells upon Ca2+ stimulation. In histological sections of human colon carcinoma CaSR was significantly reduced as compared to the level in normal colonic crypt epithelial cells. Where CaSR expression was high, strong surface staining for E-cadherin and ,-catenin was observed. Where CaSR expression was reduced, ,-catenin surface expression was likewise reduced. © 2007 Wiley-Liss, Inc. [source]

    Quantitative real-time RT-PCR for detection of disseminated tumor cells in peripheral blood of patients with colorectal cancer using different mRNA markers

    Ronny Schuster
    Abstract The detection of disseminated tumor cells in peripheral blood from colorectal cancer patients by RT-PCR could be an attractive method for selecting patients for adjuvant therapy. We here report on real-time RT-PCR assays (LightCycler) to quantitate potential mRNA markers. We investigated specimens from colon carcinoma and normal colon mucosa tissues, cell lines, blood samples from 129 patients with colorectal cancer (all stages) and 58 reference blood samples (healthy donors, persons suffering from inflammatory bowel or infectious diseases). The expression profile in tissues showed high values for CEA and CK20, whereas in cell lines ProtM was predominant. All markers were detected in reference and patient blood samples (ProtM, 22, 17%; CEA, 84, 86%; CK20, 85, 88%). After quantitative analysis, the definition of cutoff values for each marker and the combination of markers, 13% of patients were judged to have elevated marker concentrations in their blood, from which only 6 had values significantly differing from cutoff value. There were no differences between stages of disease. In the case of 19 patients, investigated prior to and 1 week after surgery, 2 samples revealed a significant postoperative increase in CEA or CK20 mRNA concentration. In spite of high expression levels in tissues and cell lines, we were not able to differentiate satisfyingly mRNA markers originating from tumor cells and those from illegitimate transcription in hematopoetic cells in blood. We conclude that either copy numbers of analyzed markers in circulating tumor cells are not sufficient for detection or, more probably, peripheral blood is not a suitable compartment for detection of tumor cells in colorectal cancer. © 2003 Wiley-Liss, Inc. [source]

    Hyaluronan synthase-3 is upregulated in metastatic colon carcinoma cells and manipulation of expression alters matrix retention and cellular growth

    Kelli M. Bullard
    Abstract HA is a glycosaminoglycan that is synthesized on the inner surface of the plasma membrane and secreted into the pericellular matrix. HA and its biosynthetic enzymes (HAS1, HAS2 and HAS3) are thought to participate in tumor growth and cancer progression. In our study, colon carcinoma cells isolated from a lymph node metastasis (SW620) produced more pericellular HA and expressed higher levels of HAS3 mRNA compared to cells isolated from a primary colon carcinoma (SW480). To assess functionality, HAS3 expression in SW620 cells was inhibited by transfection with an asHAS3 construct. Decreased HA secretion and cell-surface retention by asHAS3 transfectants were confirmed using competitive binding and particle exclusion assays. Anchorage-independent growth, a correlate of tumor growth in vivo, was assessed by colony formation in soft agar. SW620 cells stably transfected with asHAS3 demonstrated significant growth inhibition, as evidenced by fewer colonies and smaller colony area than either SW620 cells or cells transfected with vector alone. Addition of exogenous HA restored growth in asHAS3 transfectants. Thus, we demonstrate that pericellular HA secretion and retention and HAS3 expression are increased in metastatic colon carcinoma cells relative to cells derived from a primary tumor. Inhibition of HAS3 expression in these cells decreased the pericellular HA matrix and inhibited anchorage-independent growth. These data suggest that HA and HAS3 function in the growth and progression of colon carcinoma. © 2003 Wiley-Liss, Inc. [source]

    Influence of Cultivation System on Bioactive Molecules Synthesis in Strawberries: Spin-off on Antioxidant and Antiproliferative Activity

    L. D'Evoli
    ABSTRACT:, Strawberries (Fragaria ananassa,L., cv. favette) were studied to investigate the influence of cultivation practices (biodynamic, conventional) on the synthesis of bioactive molecules (ascorbic acid, ellagic acid, anthocyanins, flavonols) and to evaluate their antioxidant activity. Additionally, the,in vitro,bioactivity, in terms of antioxidant and antiproliferative activity, of the same strawberry samples in human colon carcinoma (Caco-2) cells was also studied. Compared to conventional strawberries, biodynamic fruits had a significantly higher content of ascorbic acid (P,< 0.01), pelargonidin-3-glucoside (P,< 0.05), cyanidin-3-glucoside (P,< 0.01), ellagic acid (P,< 0.01), quercetin, and kaempferol (both,P,< 0.01). Antioxidant activity of biodynamic strawberry crude extract was significantly higher than that of the conventional one (P,< 0.05); in addition, while the antioxidant activity of water-soluble fraction was very similar in both biodynamic and conventional strawberries, that of water-insoluble fraction of biodynamic fruits was significantly higher (P,< 0.05). The same crude extract of biodynamic strawberry samples effectively corresponded to an increase of bioactivity, in terms of both cellular antioxidant activity and antiproliferative activity, in Caco-2 cells differentiated to normal intestinal epithelia and in undifferentiated Caco-2, respectively. Further studies are needed to confirm whether the practice of biodynamic agriculture is likely to increase the bioactivity of other varieties of fruits and vegetables. [source]

    Radiographic herald lesion of the urinary bladder: Pictorial essay

    Michael E Flisak
    SUMMARY At cystoscopy a focal mucosal abnormality may be indicative of a pathological process extrinsic to the urinary bladder and has been termed ,the herald lesion'. The aim of the present pictorial essay was to describe the radiographic counterpart to this cystoscopic finding. Radiographic herald lesions are shown in patients with extravesical inflammatory (Crohn's disease, colonic diverticulitis and pelvic inflammatory disease) and neoplastic (colon carcinoma) processes, and urinary tract complications of these conditions are described and illustrated. [source]

    Low recurrence of preexisting extrahepatic malignancies after liver transplantation

    Daniel Benten
    The incidence of de novo malignancies is increased in organ transplant recipients, and patients with hepatic carcinomas are at high risk for tumor recurrence after liver transplantation. Data about recurrent cancer after orthotopic liver transplantation (OLT) in patients with a history of nonhepatic malignancy are very limited. We retrospectively analyzed data from 606 adult OLT recipients and identified 37 patients (6.1%) with a preexisting extrahepatic malignancy. In the same group, 43 patients (7.0%) developed de novo cancer. Preexisting malignancies included 26 solid tumors and 11 hematological malignancies, including 7 patients with Budd-Chiari syndrome due to myeloproliferative disorders (MPDs). Patients had been selected for OLT because of the expected good prognosis of their preexisting malignancy. Except for 3 patients, recipients were tumor-free at OLT. The median interval from tumor diagnosis to OLT was 44 months (range, <1-321). After a median follow-up of 66 months post transplantation (range, 4-131), all but 1 recipient with incidental colon carcinoma were free of recurrence. No patient with MPD showed leukemic transformation, whereas a patient with neurofibromatosis experienced growth of skin fibromas. Our data and an included review of published OLT recipients with preexisting malignancies have enabled us to show that recurrence rates are comparable for nontransplanted patients and renal-transplant recipients. In conclusion, cancer recurrence is low if OLT recipients are carefully selected. Therefore, previous extrahepatic malignancy should not be considered a contraindication for OLT per se, but the oncologic/hematologic prognosis should be considered, particularly with respect to the current 5-year survival rate of OLT. Liver Transpl, 2008. © 2008 AASLD [source]

    3D MR angiography of intratumoral vasculature using a novel macromolecular MR contrast agent

    Hisataka Kobayashi
    Abstract Noninvasive methods to visualize blood flow in the intratumoral vasculature have not previously been studied. In the present study, the use of a novel intravascular MR contrast agent with a generation-6 polyamidoamine dendrimer core (G6-(1B4M-Gd)192; MW: 175kD) was investigated, and the vasculature in experimental tumors was visualized using 3D MR angiography (MRA). Xenografted tumors in nude mice of two different histologies,KT005 (human osteogenic sarcoma) and LS180 (human colon carcinoma),were used to obtain 3D MRA using G6-(1B4M-Gd)192 and Gd-DTPA. The contrast MR sectional images were correlated with the corresponding histological sections. The intratumoral vasculature in the KT005 tumor was clearly visualized by 3D MRA, which became more evident with the growth of the tumor xenograft. In contrast, the intratumoral vasculature in the LS180 tumor was sparser and much less developed than that in KT005 tumors. Blood vessels with a diameter as small as 100 ,m based on histology were visualized using 0.033 mmol Gd/kg of G6-(1B4M-Gd)192. In conclusion, intratumoral vasculature with a 100-,m diameter was visualized better using 3D MRA with G6-(1B4M-Gd)192 than with Gd-DTPA. Magn Reson Med 46:579,585, 2001. © 2001 Wiley-Liss, Inc. [source]

    Expression of bone morphogenetic proteins in colon carcinoma with heterotopic ossification

    Nobuhiro Imai
    Here we report the case of a 50-year-old woman with adenocarcinoma of the colon, showing heterotopic ossification. The patient was referred to our hospital for investigation of anemia secondary to occult gastrointestinal blood loss. By colonoscopy, an irregular polypoid mass was found in the ascending colon. A biopsy of the lesion revealed moderately to poorly differentiated adenocarcinoma with heterotopic ossification. A right hemicolectomy was done and revealed areas of heterotopic bone within the tumor, but no ossification was evident in the metastatic lesions within the mesenteric lymph nodes. The formation of heterotopic bone in gastrointestinal tumors is rare and its exact mechanism is unknown. Immunohistochemical localization of bone morphogenetic proteins (BMP), known to be primary inducers of new bone formation, was determined. BMP-5 and -6 were prominent in the cytoplasm of tumor cells, and they stained weakly in osteoblast-like cells adjacent to newly formed bone. Cytoplasmic staining for BMP-2 and -4 was weak in tumor cells, osteoblast-like cells, and stromal fibroblast cells. BMP may play an important role in heterotopic ossification in colon adenocarcinoma. [source]

    Antioxidant and cytotoxic activities of Hypericum sp. on brine shrimps and human cancer cell lines

    M. Couladis
    Abstract Ten different samples of five Hypericum sp. were tested on brine shrimps, human colon carcinoma and human hepatoma cell lines for their cytotoxic activities. H. triquetrifolium Turra. (Rafina) showed the highest activity (LC50,=,22,mg/mL) on brine shrimps, while the extracts of the other nine samples showed significant to moderate activities (LC50 from 37 to 107,mg/mL). H. empetrifolium Wild. (Parnon) showed the highest activity in human colon carcinoma and human hepatoma cell lines, with LC50 values 29 and 25.1,mg/mL, respectively, while the LC50 values of the other samples were more than 45,mg/mL. It is very interesting to observe that most Hypericum samples showed good antioxidant activity in vitro. Copyright © 2002 John Wiley & Sons, Ltd. [source]

    Regulatory sequences of H19 and IGF2 genes in DNA-based therapy of colorectal rat liver metastases

    Patricia Ohana
    Abstract Background Malignant tumors of the liver are among the most common causes of cancer-related death throughout the world. Current therapeutic approaches fail to control the disease in most cases. This study seeks to explore the potential utility of transcriptional regulatory sequences of the H19 and insulin growth factor 2 (IGF2) genes for directing tumor-selective expression of a toxin gene (A fragment of diphtheria toxin), delivered by non-viral vectors. Methods The therapeutic potential of the toxin vectors driven by the H19 and the IGF2-P3 regulatory sequences was tested in a metastatic model of rat CC531 colon carcinoma in liver. Results Intratumoral injection of these vectors into colon tumors implanted in the liver of rats induced an 88% and a 50% decrease respectively in the median tumor volume as compared with the control groups. This therapeutic action was accompanied by increased necrosis of the tumor. Importantly, no signs of toxicity were detected in healthy animals after their treatment by the toxin expression vectors. Conclusions DT-A was preferentially expressed in liver metastases after being transfected with H19 or IGF2-P3 promoter-driven DT-A expression plasmids, causing a very significant inhibition of tumor growth as a result of its cytotoxic effect. Our findings strongly support the feasibility of our proposed therapeutic strategy, which may contribute to open new gene therapeutic options for human liver metastases. Copyright © 2004 John Wiley & Sons, Ltd. [source]

    Tumor volume of colon carcinoma is related to the invasive pattern but not to the expression of cell adhesion proteins

    APMIS, Issue 3 2009
    Tumor volume increases during growth and due to tumor progression various mutations appear that may cause phenotypic changes. The invasive pattern may thus be affected resulting in a more disorganized growth. This phenomenon might be due to mutations in the genome of the adhesion proteins, which are responsible for the structural integrity of epithelial tissue. Tumor volume was assessed in whole mount sections of 33 colon carcinomas using Cavalieri's principle. Images from the entire invasive border were captured and used for calculating the irregularity of the border (Complexity Index). The expression of the adhesion proteins E-cadherin, ,-catenin, Claudin 2 and Occludin was assessed after immunohistochemical staining of two randomly selected areas of the invasive front of the tumor. Statistical significance for differences in volume was obtained for tumor Complexity Index, tumor stage (pT) and lymph node status (pN). Expression of adhesion proteins was significantly perturbed in the tumors compared with normal mucosa but only infrequently correlated to tumor differentiation or invasive pattern. The results show that when tumor volume increases the invasive pattern becomes more irregular which is compatible with tumor progression. A direct contribution of adhesion protein derangement to this process appears to be insignificant. [source]

    Synthesis and Cytotoxic Evaluation of 6-(3-Pyrazolylpropyl) Derivatives of 1,4-Naphthohydroquinone-1,4-diacetate

    ARCHIV DER PHARMAZIE, Issue 10 2009
    Aurora Molinari
    Abstract Several new 6-(3-pyrazolylpropyl) derivatives of 1,4-naphthohydroquinone-1,4-diacetate (NHQ-DA) have been prepared by chemical modifications of the Diels,Alder adduct of ,-myrcene and 1,4-benzoquinone. All these new compounds and precursors have been evaluated in vitro for their cytotoxicity against cultured human cancer cells of MB-231 breast-adeno carcinoma, A-549 lung carcinoma, and HT-29 colon carcinoma. GI50 values ranged in and below the micromolar concentration level. [source]

    Inhibition of human telomerase reverse transcriptase by nonsteroidal antiinflammatory drugs in colon carcinoma

    CANCER, Issue 6 2006
    Hua He M.Phil.
    Abstract BACKGROUND Telomerase activation, which is observed in most human cancers, plays an important role in carcinogenesis. Human telomerase reverse transcriptase (hTERT) is a subunit of telomerase that is essential for telomerase activity. The aim of the study was to investigate whether nonsteroidal antiinflammatory drugs (NSAIDs) inhibit telomerase activity and hTERT. METHODS Four colon carcinoma cell lines, HT-29, COLO205, CRL-2134, and SW1116, were used in the experiments. Polymerase chain reaction-based telomeric repeat amplification (TRAP) enzyme-linked immunosorbent assay (ELISA) was used to measure telomerase activity in the cells after treatment with aspirin, indomethacin, or SC-236 (a specific cyclooxygenase-2 [COX-2] inhibitor). Expression of hTERT mRNA and protein was detected by reverse transcription,polymerase chain reaction (RT-PCR) and Western blotting, respectively. The dual luciferase reporter assay was performed to identify the potential cis-response elements to NSAIDs in the promoter region of hTERT. RESULTS Aspirin, indomethacin, and SC-236 inhibited telomerase activity in HT-29, COLO205, and CRL-2134 cell lines, but not in the SW1116 cell line. NSAIDs inhibited hTERT mRNA and protein expression through suppression of hTERT transcriptional activity. The hTERT promoter fragment ,145 to ,330 basepairs (bp) upstream of the ATG starting site was sufficient to respond to the NSAID-induced inhibitory effect and the inhibition was COX-2-independent. CONCLUSION NSAIDs inhibit telomerase activity at hTERT transcriptional, mRNA, and protein levels in colon carcinoma cells. The hTERT promoter fragment ,145 to ,330 bp may be the cis-response element to NSAIDs. Cancer 2006. © 2006 American Cancer Society. [source]

    Pathologic features of endometrial carcinoma associated with HNPCC

    CANCER, Issue 1 2006
    A comparison with sporadic endometrial carcinoma
    Abstract BACKGROUND Endometrial carcinoma is a common malignancy in hereditary nonpolyposis colorectal carcinoma (HNPCC). Like colon carcinoma, endometrial carcinoma is diagnosed at an earlier age in women with HNPCC. In contrast to colon carcinoma, the pathologic features of endometrial carcinoma in HNPCC have not been studied in detail. It was the purpose of this study to pathologically characterize a series of HNPCC associated endometrial carcinomas. METHODS Fifty women with HNPCC and endometrial carcinoma were analyzed from four different hereditary cancer registries. H&E stained slides and pathology reports were reviewed for clinically important pathologic features of endometrial carcinoma. These results were compared with those for two different groups of sporadic endometrial carcinoma , women younger than age 50 years (n = 42) and women of all ages with tumors demonstrating microsatellite instability (MSI-high) secondary to methylation of MLH1 (n = 26). RESULTS Nearly one-fourth of HNPCC patients in this study had endometrial tumors with pathologic features that would require adjuvant therapy after hysterectomy. There was a trend toward the HNPCC patients having more nonendometrioid tumors; all of these patients were carriers of MSH2 mutations. Such nonendometrioid tumors were extremely rare in the MLH1 methylated group. A subset of MLH1 methylated sporadic tumors demonstrated a unique, ,undifferentiated' histology that was not observed in HNPCC or the young group. CONCLUSION Data suggest a genotype,phenotype relation in which microsatellite instability resulting from MLH1 methylation is almost exclusively associated with classical or ,undifferentiated' endometrioid tumors, whereas microsatellite instability secondary to MSH2 mutation can result in a more variable histologic spectrum of endometrial carcinoma. Cancer 2006. © 2005 American Cancer Society. [source]

    Selecting patients for flexible sigmoidoscopy

    CANCER, Issue 6 2005
    Determinants of incomplete depth of insertion
    Abstract BACKGROUND Flexible sigmoidoscopy (FS) is an effective method to prevent and reduce mortality from colorectal carcinoma (CRC). Incomplete depth of insertion (IDI) during FS may result in missed polyps and carcinomas. To determine whether it is possible to predict IDI, the authors analyzed factors that affected the depth of insertion in FS. METHODS For the current study, FS results were recorded prospectively over a 5-year period. A questionnaire was administered to the patient by the investigator prior to FS to collect data, including age, gender, weight, comorbid illnesses, history of prior abdominal and pelvic surgeries, family history of colon carcinoma or polyps, and prior FS or colonoscopies. The depth of insertion of the flexible sigmoidoscope from the anal verge, which was defined as the reading on the outside of the instrument at its maximal insertion, was measured in centimeters. IDI was defined as a depth of insertion < 50 cm. Classification and regression tree analysis was used to develop a model that included variables predictive of IDI. RESULTS The best classification tree included gender, age < 69 years (in women), and a history of hysterectomy. Men had a < 5% risk of an IDI and women age < 69 years without a hysterectomy fared as well (6.6%). Older women and younger women who underwent hysterectomy had higher rates of IDI (29.2% and 22.3%, respectively.) CONCLUSIONS The authors developed a model based on age, gender, and hysterectomy status that, after further validation, may be useful for predicting which patients likely will have an incomplete examination. In those patients who have a high probability of IDI, the choice can be made to offer colonoscopy or perform FS under sedation, with analgesia, or with the help of distraction techniques. Cancer 2005. © 2005 American Cancer Society. [source]

    Two schedules of second-line irinotecan for metastatic colon carcinoma

    CANCER, Issue 11 2004
    Economic evaluation of a randomized trial
    Abstract BACKGROUND In a recently reported, randomized trial, it was found that a regimen of irinotecan once every 3 weeks for patients with advanced colorectal carcinoma was associated with a lower incidence of severe diarrhea compared with weekly treatment, and both regimens had similar efficacy. METHODS Resource utilization was captured prospectively for all 291 patients who were included in the trial. Utilities were estimated by transformation of the global quality-of-life (QOL) item on the Eastern Organization for Research and Treatment of Cancer QLQ-C30 instrument. RESULTS Patients in the every-3-week arm incurred an average incremental cost of $1362, because they received higher average weekly doses and because the every-3-week regimen resulted in less toxicity, allowing delivery of 97% of the planned doses compared with delivery of only 75% of the planned doses in the weekly arm. This lower toxicity also resulted in offsetting savings from decreased hospitalization and less requirement for supportive medications. Non-chemotherapy-related treatment administration costs also were lower, because the every-3-week regimen could be delivered with half the number of infusions. Utility declined less in the every-3-week arm, resulting in a saving of 6.3 quality-adjusted days. The base-case cost:utility ratio was $78,627 per quality-adjusted life year for patients on the every-3-week schedule. However, that ratio was very sensitive to the cost of irinotecan. CONCLUSIONS The schedule of irinotecan once every 3 weeks schedule was more costly but achieved lower toxicity, resulting in modestly improved utility. The cost-per-utility ratio was comparable to other commonly accepted contemporary treatments. Cancer 2004. © 2004 American Cancer Society. [source]

    Familial association of specific histologic types of ovarian malignancy with other malignancies,

    CANCER, Issue 7 2004
    Justo Lorenzo Bermejo Ph.D.
    Abstract BACKGROUND Population-based data on the familial association of specific histologic types of ovarian malignancy with other malignancies are limited. Such data may help to elucidate etiologic differences among histologic types of ovarian malignancy. METHODS The nationwide Swedish Family-Cancer Database, which includes 10.3 million individuals and 20,974 ovarian carcinomas, was used to calculate standardized incidence ratios and 95% confidence intervals for age- and histology-specific ovarian malignancies in women whose parents or siblings were affected with malignancies at the most common disease sites. RESULTS Ovarian malignancy was found to be associated with ovarian, laryngeal, breast, endometrial, liver, and colon carcinoma, as well as myeloma; epithelial ovarian malignancy was found to be associated with ovarian, endometrial, and skin malignancies and with melanoma and myeloma; papillary serous cystadenocarcinoma was found to be associated with ovarian and skin malignancies and with myeloma; and endometrioid carcinoma was found to be associated with endometrial, ovarian, and prostate malignancies and with melanoma. For younger women (ages 40,45 years) whose mothers were affected with endometrial malignancies, the risk of developing endometrioid carcinoma was slightly greater than the risk of developing papillary serous cystadenocarcinoma. CONCLUSIONS Specific types of ovarian malignancy may be associated with specific familial disease sites, with such associations depending on age at diagnosis; the strength of the observed associations varied according to histology. Associations were found between endometrioid carcinoma and endometrial malignancy and between serous carcinoma and Hodgkin disease. Cancer 2004;100:1507,14. © 2004 American Cancer Society. [source]

    The replication error phenotype is associated with the development of distant metastases in hormonally treated patients with breast carcinoma

    CANCER, Issue 5 2004
    Anees Chagpar M.D., M.Sc.
    Abstract BACKGROUND The positive replication error (RER+) phenotype defines a distinct subgroup of tumors with specific clinical, pathologic, and molecular features that have been documented well in hereditary nonpolyposis colon carcinoma (HNPCC). More recently, this phenotype also has been described in breast carcinoma. METHODS To determine the effect of RER phenotype on prognosis in patients with breast carcinoma, the authors examined matched archival tumor and normal tissue from 100 women with Stage I and Stage II breast carcinoma, all of whom were treated with hormonal therapy. Patients had been followed for a minimum of 5 years or until death. Seven microsatellite loci were examined, including hMLH1 (3p22, D3S1611), hMSH2 (2p16, D2S123), NM23-H1 (17q21), TP53-Dint (17p13), TP53-Penta (17p13), APC (5q21, D5S346), and HPC1 (1q24, D1S2883). The RER+ phenotype was defined as the presence of allelic shifts at three of the seven loci examined. RESULTS Twenty-five percent of patients were classified with the RER+ phenotype based on these criteria. The two groups, women with positive RER status and women with negative RER status, were comparable in terms of other factors that may influence prognosis: age, tumor size, lymph node status, disease stage, and estrogen receptor status. The development of distant metastases to the lung, liver, or brain was correlated significantly with the positive RER phenotype, with a relative risk of 2.625 (95% confidence interval, 1.059,6.057). CONCLUSIONS The presence of high-frequency RER+ may predict for the development of distant metastatic disease in patients with early-stage breast carcinoma whoa re treated with hormonal therapy. Cancer 2004;100:913,9. © 2004 American Cancer Society. [source]

    Improved prediction of recurrence after curative resection of colon carcinoma using tree-based risk stratification

    CANCER, Issue 5 2004
    Martin 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]

    Influence of body mass index on outcomes and treatment-related toxicity in patients with colon carcinoma

    CANCER, Issue 3 2003
    Jeffrey A. Meyerhardt M.D., M.P.H.
    Abstract BACKGROUND Obesity is a risk factor for the development of colon carcinoma. The influence of body mass index (BMI) on long-term outcomes and treatment-related toxicity in patients with colon carcinoma has not been well characterized. METHODS This cohort study was conducted within a large, randomized adjuvant chemotherapy trial of 3759 men and women with high-risk, Stage II and Stage III colon carcinoma who were treated between 1988 and 1992 throughout the United States. With a median follow-up of 9.4 years, the authors examined the influence of BMI on disease recurrence, overall survival, and treatment-related toxicity. RESULTS Compared with women of normal weight (BMI, 21.0,24.9 kg/m2), obese women with colon carcinoma (BMI , 30.0 kg/m2) experienced significantly worse overall mortality (hazard ratio [HR], 1.34; 95% confidence interval [95% CI], 1.07,1.67) and a nonsignificant increase in the risk of disease recurrence (HR, 1.24; 95% CI, 0.98,1.59). The influence of BMI among women was not related to any differences in chemotherapy dose-intensity across categories of BMI. In contrast, BMI was not related significantly to long-term outcomes among male patients in this cohort. Among all study participants, obese patients had significantly lower rates of Grade 3,4 leukopenia and lower rates of any Grade , 3 toxicity compared with patients of normal weight. CONCLUSIONS Among women with Stage II,III colon carcinoma, obesity was associated with a significant increase in overall mortality as well as a borderline significant increase in disease recurrence. Nonetheless, obesity was not associated with any increase in chemotherapy-related toxicity. Cancer 2003;98:484,95. © 2003 American Cancer Society. DOI 10.1002/cncr.11544 [source]

    In vivo and in vitro Interactions between Human Colon Carcinoma Cells and Hepatic Stellate Cells

    CANCER SCIENCE, Issue 12 2000
    Sadatoshi Shimizu
    Stromal reaction is important for the growth of cancer both in primary and metastatic sites. To demonstrate this reaction during the hepatic metastasis of human colon carcinoma, we histologically investigated alterations to the distribution and phenotype of hepatic stellate cells (HSCs), the only mesenchymal cells in the liver parenchyma, using a nude mouse model. Intrasplenically injected colon carcinoma LM-H3 cells migrated into the space of Disse and underwent proliferation, in close association with hepatocytes and HSCs, at 2 days. At 14 days, HSCs were accumulated around the tumor mass and expressed ,-smooth muscle actin, a marker for HSC activation. We next investigated in vitro the growth factors involved in the interactions between LM-H3 cells and HSCs. Conditioned medium of rat HSCs which underwent culture-induced activation contained platelet-derived growth factor (PDGF)-AB, hepatocyte growth factor (HGF) and transforming growth factor (TGF),, and could augment LM-H3-cell proliferation and migration. Neutralizing antibodies against PDGF-AA and PDGF-BB and those against PDGF-BB and HGF inhibited proliferation and migration, respectively, of LM-H3 cells, whereas antibody against TGF-, had no effect. LM-H3 cells expressed PDGF receptors-, and -, and c-met. Conditioned medium of LM-H3 cells contained PDGF-AB, and could enhance HSC proliferation and migration. This augmenting effect was suppressed by treatment with anti-PDGF-AB antibody. The present study has demonstrated that bidirectional interactions involving PDGF and HGF take place in vitro between colon carcinoma cells and HSCs, raising the possibility that similar interactions might be involved in the stromal reaction during hepatic metastasis. [source]

    Human colon cancer epithelial cells harbour active HEDGEHOG-GLI signalling that is essential for tumour growth, recurrence, metastasis and stem cell survival and expansion

    Frédéric Varnat
    Abstract Human colon cancers often start as benign adenomas through loss of APC, leading to enhanced ,CATENIN (,CAT)/TCF function. These early lesions are efficiently managed but often progress to invasive carcinomas and incurable metastases through additional changes, the nature of which is unclear. We find that epithelial cells of human colon carcinomas (CCs) and their stem cells of all stages harbour an active HH-GLI pathway. Unexpectedly, they acquire a high HEDGEHOG-GLI (HH-GLI) signature coincident with the development of metastases. We show that the growth of CC xenografts, their recurrence and metastases require HH-GLI function, which induces a robust epithelial-to-mesenchymal transition (EMT). Moreover, using a novel tumour cell competition assay we show that the self-renewal of CC stem cells in vivo relies on HH-GLI activity. Our results indicate a key and essential role of the HH-GLI1 pathway in promoting CC growth, stem cell self-renewal and metastatic behavior in advanced cancers. Targeting HH-GLI1, directly or indirectly, is thus predicted to decrease tumour bulk and eradicate CC stem cells and metastases. [source]

    REG1A expression is a prognostic marker in colorectal cancer and associated with peritoneal carcinomatosis

    Christian Astrosini
    Abstract By expression profiling of early staged colon carcinomas, we found regenerating islet-derived 1 alpha (REG1A) to be upregulated in patients with an unfavorable clinical outcome. For validation, REG1A expression was quantified in another colorectal cancer (CRC) patient cohort by Taqman PCR. Aside from tumor and normal tissue from 63 nonpretreated CRC patients, 31 mucosa biopsies from healthy individuals as well as 22 adenomas were included in the investigation. REG1A was significantly upregulated in tumor specimens (p < 0.001) and adenoma (p < 0.01) as compared to normal colorectal tissue. REG1A expression in normal peritumoral tissue in turn proved to be significantly elevated compared to mucosa from healthy individuals (p < 0.01). Determination of REG1A expression might be useful for early tumor diagnosis with a sensitivity of 90.6%, and a specificity of 77.9%. REG1A expression was significantly increased in tumors with peritoneal carcinomatosis (p < 0.01). Moreover, REG1A turned out to be a significant predictor of disease-free survival (p < 0.05). In conclusion, we present evidence that REG1A is a molecular marker of prognostic value and is associated with peritoneal carcinomatosis in CRC. REG1A turned out to be already significantly raised in peritumoral normal tissue compared to mucosa from healthy individuals, suggesting a molecular field effect of secreted REG1A. © 2008 Wiley-Liss, Inc. [source]

    Angiogenesis and Interstitial Pressure in a Rat Tumour Model

    H. Hünigen
    Introduction and Aim:, Angiogenesis, the formation of new blood vessels, is a crucial process in physiological and pathological growth. Pathological angiogenesis is responsible for growth and metastasis of solid tumours, and, when blocked, improves prognosis. As a result of the angiogenic cascade in solid tumours an irregular, leaky capillary network develops. The aim of the present study was to define malignant tumours' vascular characteristics and reveal functional anatomy by quantification of the microvasculature and interstitial pressure (IP) in relation to tumour fluid dynamics as visualized by contrast enhanced magnetic resonance imaging (MRI). Material and Methods:, Dynamic MRI and measurement of the IP was performed in 21 rats implanted with colon carcinomas subcutaneously. Angiogenesis was studied by morphometry of the capillaries, and immunolocalization of the angiogenic factor VEGF and VEGF-Receptor 2. Results and Conclusions:, Histology, immunohistochemistry and MRI confirmed concentric arrangement of 4 tumour zones. The tumour margin included loose connective tissue with abundant mononuclear cells. Many large microvessels were seen in this most intensely vascularized zone. IP measurement in this zone was adjusted to the zero level. Diameter of the peripheral zone of vital cells measured 1.3 mm. Capillaries were smaller and sparse. Dynamic MRI revealed peripheral washout of the contrast agent in this zone. After an initial increase of the signal intensity a hypo-intense rim was formed within a few minutes. The intermediate region was characterized by islands of vital tumour cells containing 3% capillaries (hot spots). The innermost area, the necrotic zone, took 35% of the total tumour area with less than 0.5% vessels. The IP increased from the periphery to the centre. VEGF and VEGF-receptor 2 was found in the vessels of the tumour margin and vital tumour cells of the peripheral zone. From this can be concluded that the peripheral washout phenomenon seems to be correlated with elevated interstitial pressure and increased capillary density and therefore may be a reliable sign of malignancy. [source]

    Mutational analysis of mononucleotide repeats in dual specificity tyrosine phosphatase genes in gastric and colon carcinomas with microsatellite instability

    APMIS, Issue 5 2010
    Song SY, Kang MR, Yoo NJ, Lee SH. Mutational analysis of mononucleotide repeats in dual specificity tyrosine phosphatase genes in gastric and colon carcinomas with microsatellite instability. APMIS 2010; 118: 389,93. Coordinated protein phosphorylation and dephosphorylation are crucial in the regulation of cell signaling, and disruption of the coordination is known to play important roles in cancer development. Recent reports revealed that classical protein tyrosine phosphatase (PTP)-encoded genes are somatically mutated in human colorectal cancer. However, data on dual specificity phosphatase (DPTP) gene mutations in human cancers are lacking. By analyzing a public genomic database, we found that five DPTP genes, CDC14A, MTM1, MTMR3, SSH1, and SSH2, have mononucleotide repeats in their coding DNA sequences. To see whether these genes are mutated in cancers with microsatellite instability (MSI), we analyzed the mononucleotide repeats in 26 gastric cancers (GC) with MSI (MSI-H), 12 GC with low MSI (MSI-L), 45 GC with stable MSI (MSS), 33 colorectal cancers (CRC) with MSI-H, 14 CRC with MSI-L, and 45 CRC with MSS by single-strand conformation polymorphism (SSCP). We found CDC14A and MTMR3 mutations in five and one cancer (s), respectively. These mutations were detected in MSI-H cancers, but not in MSI-L or MSS cancers. The GC and CRC with MSI-H harbored the mutations in 15% and 6%, respectively. The CDC14A and MTMR3 mutations detected in the GC and CRC were deletion or duplication mutations of one base in the nucleotide repeats that would result in premature stops of the amino acid syntheses. Our data show that frameshift mutations of DPTP genes in MSI-H cancers occur at moderate frequencies. The data suggested that alterations in the CDC14A and MTMR3 genes may play a role in the development of GC and CRC with MSI-H by deregulating phosphatase functions possibly together with mutations of classical PTP genes. [source]

    Tumor volume of colon carcinoma is related to the invasive pattern but not to the expression of cell adhesion proteins

    APMIS, Issue 3 2009
    Tumor volume increases during growth and due to tumor progression various mutations appear that may cause phenotypic changes. The invasive pattern may thus be affected resulting in a more disorganized growth. This phenomenon might be due to mutations in the genome of the adhesion proteins, which are responsible for the structural integrity of epithelial tissue. Tumor volume was assessed in whole mount sections of 33 colon carcinomas using Cavalieri's principle. Images from the entire invasive border were captured and used for calculating the irregularity of the border (Complexity Index). The expression of the adhesion proteins E-cadherin, ,-catenin, Claudin 2 and Occludin was assessed after immunohistochemical staining of two randomly selected areas of the invasive front of the tumor. Statistical significance for differences in volume was obtained for tumor Complexity Index, tumor stage (pT) and lymph node status (pN). Expression of adhesion proteins was significantly perturbed in the tumors compared with normal mucosa but only infrequently correlated to tumor differentiation or invasive pattern. The results show that when tumor volume increases the invasive pattern becomes more irregular which is compatible with tumor progression. A direct contribution of adhesion protein derangement to this process appears to be insignificant. [source]

    Secondary effects induced by the colon carcinogen azoxymethane in BDIX rats,

    APMIS, Issue 6 2004
    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 tumours which increased with longer latency periods. The renal tumours were only found in female rats, and this indicates a possible relation to sex hormones. We therefore analyzed both male and female kidneys for the expression of estrogen and progesterone receptors by immunohistochemical methods. A positive nuclear reaction for estrogen receptor was present in most tumour cells in all tumours and occasionally in nuclei of entrapped tubular cells, but never in glomeruli. Normal appearing renal tissue from female rats showed no positive reaction, but in male rats a slight nuclear reaction was seen in tubuli in the peripheral part of the medulla. A similar pattern was seen for progesterone receptors, but less pronounced. No rats developed tumours in the external ear canal, which is in contrast to studies performed in other rat strains. This may therefore be strain related. In order to reduce the secondary effects of the induction of colon cancer by AOM, it is advisable to use male rats only and a maximum latency period of 32 weeks. [source]

    Model-based prediction of defective DNA mismatch repair using clinicopathological variables in sporadic colon cancer patients

    CANCER, Issue 7 2010
    Frank Sinicrope MD
    Abstract BACKGROUND: Colon cancers with defective DNA mismatch repair (MMR) have a favorable prognosis and may lack benefit from 5-fluorouracil,based adjuvant chemotherapy. The authors developed models to predict MMR deficiency in sporadic colon cancer patients using routine clinical and pathological data. METHODS: TNM stage II and III colon carcinomas (n = 982) from 6 5-fluorouracil,based adjuvant therapy trials were analyzed for microsatellite instability and/or MMR protein expression. Tumor-infiltrating lymphocytes (TILs) were quantified (n = 326). Logistic regression and a recursive partitioning and amalgamation analysis were used to identify predictive factors for MMR status. RESULTS: Defective MMR was detected in 147 (15%) cancers. Tumor site and histologic grade were the most important predictors of MMR status. Distal tumors had a low likelihood of defective MMR (3%; 13 of 468); proximal tumors had a greater likelihood (26%; 130 of 506). By using tumor site, grade, and sex, the logistic regression model showed excellent discrimination (c statistic = 0.81). Proximal site, female sex, and poor differentiation showed a positive predictive value (PPV) of 51% for defective MMR. In a patient subset (n = 326), a model including proximal site, TILs (>2/high-power field), and female sex showed even better discrimination (c statistic = 0.86), with a PPV of 81%. CONCLUSIONS: Defective MMR is rare in distal, sporadic colon cancers, which should generally not undergo MMR testing. Proximal site, poor differentiation, and female sex detect 51% of tumors with defective MMR; substituting TILs for grade increases the PPV to 81%. These data can increase the efficiency of MMR testing to assist in clinical decisions. Cancer 2010. © 2010 American Cancer Society. [source]