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Sample records for sporadic colon carcinoma

  1. Dietary factors and microsatellite instability in sporadic colon carcinomas

    NARCIS (Netherlands)

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

    2003-01-01

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

  2. Clinicopathologic factors identify sporadic mismatch repair-defective colon cancers

    DEFF Research Database (Denmark)

    Halvarsson, Britta; Anderson, Harald; Domanska, Katarina

    2008-01-01

    Identification of sporadic mismatch repair (MMR)-defective colon cancers is increasingly demanded for decisions on adjuvant therapies. We evaluated clinicopathologic factors for the identification of these prognostically favorable tumors. Histopathologic features in 238 consecutive colon cancers...

  3. Clinicopathologic factors identify sporadic mismatch repair-defective colon cancers

    DEFF Research Database (Denmark)

    Halvarsson, Britta; Anderson, Harald; Domanska, Katarina

    2008-01-01

    Identification of sporadic mismatch repair (MMR)-defective colon cancers is increasingly demanded for decisions on adjuvant therapies. We evaluated clinicopathologic factors for the identification of these prognostically favorable tumors. Histopathologic features in 238 consecutive colon cancers...... and excluded 61.5% of the tumors from MMR testing. This clinicopathologic index thus successfully selects MMR-defective colon cancers. Udgivelsesdato: 2008-Feb...

  4. Medullary carcinoma of the colon

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

    2015-01-01

    Medullary carcinoma of the colon is a rare variant of colorectal cancer claimed to have a more favorable prognosis than conventional adenocarcinomas. The histopathologic appearance may be difficult to distinguish from poorly differentiated adenocarcinoma. The study aimed to evaluate the diagnostic...... differences in CK20 (p = 0.005) expression and in the rate of BRAF mutations (p = 0.0035). In conclusion, medullary carcinomas of the colon are difficult to discriminate from poorly differentiated adenocarcinoma even with the help of immunohistochemical and molecular analyses. This raises the question whether...

  5. Laparoscopic colectomy for transverse colon carcinoma.

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    Zmora, O; Bar-Dayan, A; Khaikin, M; Lebeydev, A; Shabtai, M; Ayalon, A; Rosin, D

    2010-03-01

    Laparoscopic resection of transverse colon carcinoma is technically demanding and was excluded from most of the large trials of laparoscopic colectomy. The aim of this study was to assess the safety, feasibility, and outcome of laparoscopic resection of carcinoma of the transverse colon. A retrospective review was performed to identify patients who underwent laparoscopic resection of transverse colon carcinoma. These patients were compared to patients who had laparoscopic resection for right and sigmoid colon carcinoma. In addition, they were compared to a historical series of patients who underwent open resection for transverse colon cancer. A total of 22 patients underwent laparoscopic resection for transverse colon carcinoma. Sixty-eight patients operated for right colon cancer and 64 operated for sigmoid colon cancer served as comparison groups. Twenty-four patients were identified for the historical open group. Intraoperative complications occurred in 4.5% of patients with transverse colon cancer compared to 5.9% (P = 1.0) and 7.8% (P = 1.0) of patients with right and sigmoid colon cancer, respectively. The early postoperative complication rate was 45, 50 (P = 1.0), and 37.5% (P = 0.22) in the three groups, respectively. Conversion was required in 1 (5%) patient in the laparoscopic transverse colon group. The conversion rate and late complications were not significantly different in the three groups. There was no significant difference in the number of lymph nodes harvested in the laparoscopic and open groups. Operative time was significantly longer in the laparoscopic transverse colectomy group when compared to all other groups (P = 0.001, 0.008, and transverse colectomy, respectively). The results of laparoscopic colon resection for transverse colon carcinoma are comparable to the results of laparoscopic resection of right or sigmoid colon cancer and open resection of transverse colon carcinoma. These results suggest that laparoscopic resection of transverse

  6. Colon carcinoma in the adolescent.

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    Sebbag, G; Lantsberg, L; Arish, A; Levi, I; Hoda, J

    1997-07-01

    Carcinoma of the colon in the adolescent, although an uncommon disease, is usually virulent and has a poorer prognosis than in older patients. We report three cases of colon cancer in youngsters less than 19 years old. Two of them, who were diagnosed and treated early, are presently considered cured; the third died 3 months after surgery. All underwent surgery and adjuvant therapy. In an extensive review of the literature, we found a consensus as to the rarity, virulence and poor prognosis of colon cancer in the younger population. The commonest histological pattern is an aggressive, mucin-producing adenocarcinoma. Predisposing conditions include familial polyposis coli and ulcerative colitis. We also found that a low socioeconomic status could be a predisposing factor. Survival obviously depends on the extent of the disease at diagnosis, and the shorter the delay in diagnosis, the better the prognosis. The therapeutic approach must be aggresive in both surgery and adjuvant therapy; the goal must be early diagnosis, the reward being a possibility of cure, as seen in two of our three cases.

  7. Immunohistochemistry for annexin A10 can distinguish sporadic from Lynch syndrome-associated microsatellite-unstable colorectal carcinoma.

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    Pai, Reetesh K; Shadrach, Bonnie L; Carver, Paula; Heald, Brandie; Moline, Jessica; Church, James; Kalady, Matthew F; Burke, Carol A; Plesec, Thomas P; Lai, Keith K; Gonzalo, David H; Pai, Rish K

    2014-04-01

    Differentiating sporadic microsatellite-unstable colorectal carcinoma due to MLH1 promoter hypermethylation from Lynch syndrome (LS)-associated tumors due to mutations in mismatch-repair proteins is time consuming, cost intensive, and requires advanced laboratory testing. A mutation in BRAF has been shown to be highly specific for sporadic tumors; however, a significant proportion of sporadic microsatellite-unstable tumors lack BRAF mutations. MLH1 promoter methylation analysis is subsequently used to differentiate LS and sporadic tumors, but both tests require specialized laboratories and are costly. Through previous gene expression profiling of serrated polyps, we identified annexin A10 as a protein highly expressed in sessile serrated adenomas/polyps. As these polyps give rise to the majority of sporadic microsatellite-unstable tumors, we evaluated the ability of annexin A10 expression to discriminate between LS and sporadic tumors. A marked increase in annexin A10 mRNA was observed in sporadic microsatellite-unstable tumors compared with LS tumors (378-fold increase, Pimmunohistochemistry, annexin A10 was expressed in 23/53 (43%) BRAF-mutated and 9/22 (41%) BRAF wild-type sporadic tumors. In contrast, only 3/56 (5%) LS tumors were positive for annexin A10 (Pimmunohistochemistry. Only 1/28 (4%) LS tumors with loss of MLH1 was positive for annexin A10. This patient did not have a deleterious MLH1 mutation but rather germline promoter hypermethylation of MLH1. On the basis of these results, immunohistochemistry for annexin A10 may be a useful marker to distinguish sporadic from LS-associated microsatellite-unstable colon cancer.

  8. Independent Induction of Caspase-8 and cFLIP Expression during Colorectal Carcinogenesis in Sporadic and HNPCC Adenomas and Carcinomas

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    D. M. Heijink

    2007-01-01

    Full Text Available Background: TNF-Related Apoptosis Inducing Ligand (TRAIL is a promising agent for the induction of apoptosis in neoplastic tissues. Important determinants of TRAIL sensitivity are two intracellular proteins of the TRAIL pathway, caspase-8 and its anti-apoptotic competitor cellular Flice-Like Inhibitory Protein (cFLIP. Methods: The aim of this study was to investigate basic expression of caspase-8 and cFLIP in normal colorectal epithelium (n = 20, colorectal adenomas (n = 66 and colorectal carcinomas (n = 44 using immunohistochemistry performed on both sporadic and Hereditary Non-Polyposis Colorectal Cancer (HNPCC or Lynch syndrome-associated adenomas and carcinomas. Results: Expression of both caspase-8 and cFLIP was similar in cases with sporadic and hereditary origin. Expression of caspase-8 in colorectal adenomas and carcinomas was increased when compared to normal colon tissue (P = 0.02. Nuclear, paranuclear as well as cytoplasmic localizations of caspase-8 were detected. Immunohistochemistry revealed an upregulation of cFLIP in colorectal carcinomas in comparison to normal epithelium and colorectal adenomas (P < 0.001. A large variation in the caspase-8/cFLIP ratio was observed between the individual adenomas and carcinomas. Conclusion: Caspase-8 and cFLIP are upregulated during colorectal carcinogenesis. Upregulation of caspase-8 and/or downregulation of cFLIP may be interesting approaches to maximize TRAIL sensitivity in colorectal neoplasms.

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

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    Anastasios J. Karayiannakis

    2011-05-01

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

  10. Necrotizing colitis associated with carcinoma of the colon

    International Nuclear Information System (INIS)

    Woo, Seong Ku; Lim, Jae Hoon; Kim, Soon Yong; Ahn, Chi Yul

    1982-01-01

    Necrotizing colitis associated with carcinoma of the colon, known also as obstructive colitis, is a disorder characterized by anulceration and inflammation of the colon proximal to an obstructive lesion, especially carcinoma of the rectosigmoid colon, and in rare instance, leads to acute gangrene of the colon. The authors analyzed radiologic findings in four cases of necrotizing colitis associated with carcinoma of the colon. Barium enema disclosed mucosal edema, nodular filling defects, irregularity of the colonic contour and typical thumbprinting appearance of involved colon proximal to an obstructing carcinoma of the colon. The mechanism of necrotizing colitis was briefly reviewed

  11. Melanocyte colonization and pigmentation of breast carcinoma

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  12. Ophthalmoscopy for congenital hypertrophy of the retinal pigment epithelium (CHRPE) in patients with sporadic colorectal carcinoma

    DEFF Research Database (Denmark)

    Hartvigsen, A; Myrhøj, T; Bülow, Steffen

    1995-01-01

    In order to investigate the frequency of congenital hypertrophy of the retinal pigment epithelium (CHRPE) in sporadic colorectal cancer, ophthalmoscopy was carried out in 34 patients with colorectal carcinoma without known familial disposition. CHRPE is one of the most frequent extracolonic...

  13. ATM down-regulation is associated with poor prognosis in sporadic breast carcinomas

    DEFF Research Database (Denmark)

    Bueno, R C; Canevari, R A; Villacis, R A R

    2014-01-01

    BACKGROUND: Ataxia telangiectasia-mutated (ATM) gene downexpression has been reported in sporadic breast carcinomas (BC); however, the prognostic value and mechanisms of ATM deregulation remain unclear. PATIENTS AND METHODS: ATM and miRNAs (miR-26a, miR-26b, miR-203, miR-421, miR-664, miR-576-5p...

  14. Synchronous colon and gastric advanced carcinomas

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    Giuliani, A.; Demoro, M.; Corona, M.; Di Bari, M.; Ricciardulli, T.; Galati, G. [La Sapienza Univ., Rome (Italy). Dept. of Surgery Pietro Valdoni; Ciardi, A. [La Sapienza Univ., Rome (Italy). Dept. of Experimental Medicine and Pathology

    2005-03-15

    An unusual case of advanced synchronous colon and gastric carcinoma is described. A 36 year old female was admitted to our Department with a stenosing right colon cancer diagnosed at endoscopy which was performed for lower crampy abdominal pain and gross blood in the stool. Multiple colon polyps, distal to the tumor, were also detected. On preoperative abdominal computed tomography, a stenosing right colon cancer, without evidence of abdominal diffusion, was confirmed. At laparotomy, in addition to colon cancer, an antral gastric cancer was incidentally found. En bloc hemi gastrectomy and subtotal colectomy were performed. Digestive continuity was restored by gastrojejunal and ileosigmoid anastomoses. At histology, a poorly differentiated gastric adenocarcinoma with signet ring-cell component (pT2, pN0; stage IB) and a moderately differentiated colon adenocarcinoma with a tubulovillous component (pT3, pN1; stage III, Stage Dukes C) were revealed. Both tumors showed a low expression of p53 and c-erb2 oncoproteins. No genetic defect was identified in the APC and MMR genes. The patient is alive, without recurrence, two years after the operation.

  15. Synchronous colon and gastric advanced carcinomas

    International Nuclear Information System (INIS)

    Giuliani, A.; Demoro, M.; Corona, M.; Di Bari, M.; Ricciardulli, T.; Galati, G.; Ciardi, A.

    2005-01-01

    An unusual case of advanced synchronous colon and gastric carcinoma is described. A 36 year old female was admitted to our Department with a stenosing right colon cancer diagnosed at endoscopy which was performed for lower crampy abdominal pain and gross blood in the stool. Multiple colon polyps, distal to the tumor, were also detected. On preoperative abdominal computed tomography, a stenosing right colon cancer, without evidence of abdominal diffusion, was confirmed. At laparotomy, in addition to colon cancer, an antral gastric cancer was incidentally found. En bloc hemi gastrectomy and subtotal colectomy were performed. Digestive continuity was restored by gastrojejunal and ileosigmoid anastomoses. At histology, a poorly differentiated gastric adenocarcinoma with signet ring-cell component (pT2, pN0; stage IB) and a moderately differentiated colon adenocarcinoma with a tubulovillous component (pT3, pN1; stage III, Stage Dukes C) were revealed. Both tumors showed a low expression of p53 and c-erb2 oncoproteins. No genetic defect was identified in the APC and MMR genes. The patient is alive, without recurrence, two years after the operation

  16. Local stratification of colon and rectum carcinomas by computerized tomography

    International Nuclear Information System (INIS)

    Amaguana, Fanny

    2002-01-01

    The purpose of this study is to determine the value of computerized tomography water enema versus conventional computerized tomography as methods to diagnose the colon and rectum carcinomas. One hundred patients with colon cancer were treated. (The author)

  17. Deficient expression of DNA repair enzymes in early progression to sporadic colon cancer

    Science.gov (United States)

    2012-01-01

    Background Cancers often arise within an area of cells (e.g. an epithelial patch) that is predisposed to the development of cancer, i.e. a "field of cancerization" or "field defect." Sporadic colon cancer is characterized by an elevated mutation rate and genomic instability. If a field defect were deficient in DNA repair, DNA damages would tend to escape repair and give rise to carcinogenic mutations. Purpose To determine whether reduced expression of DNA repair proteins Pms2, Ercc1 and Xpf (pairing partner of Ercc1) are early steps in progression to colon cancer. Results Tissue biopsies were taken during colonoscopies of 77 patients at 4 different risk levels for colon cancer, including 19 patients who had never had colonic neoplasia (who served as controls). In addition, 158 tissue samples were taken from tissues near or within colon cancers removed by resection and 16 tissue samples were taken near tubulovillous adenomas (TVAs) removed by resection. 568 triplicate tissue sections (a total of 1,704 tissue sections) from these tissue samples were evaluated by immunohistochemistry for 4 DNA repair proteins. Substantially reduced protein expression of Pms2, Ercc1 and Xpf occurred in field defects of up to 10 cm longitudinally distant from colon cancers or TVAs and within colon cancers. Expression of another DNA repair protein, Ku86, was infrequently reduced in these areas. When Pms2, Ercc1 or Xpf were reduced in protein expression, then either one or both of the other two proteins most often had reduced protein expression as well. The mean inner colon circumferences, from 32 resections, of the ascending, transverse and descending/sigmoid areas were measured as 6.6 cm, 5.8 cm and 6.3 cm, respectively. When combined with other measurements in the literature, this indicates the approximate mean number of colonic crypts in humans is 10 million. Conclusions The substantial deficiencies in protein expression of DNA repair proteins Pms2, Ercc1 and Xpf in about 1 million

  18. Sporadic minute medullary thyroid carcinoma with a double RET mutation: A case report.

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    Yamamoto, Hiroyuki; Ishii, Jun; Chiba, Tomohiro; Nakazato, Yoko; Hirano, Kouichi; Kamma, Hiroshi

    2017-11-01

    We describe a 74-year-old man with a nodular goiter accompanied by an incidental sporadic minute medullary thyroid carcinoma (MTC). Histopathologically, the MTC was a well-defined 1.7 mm tumor in the upper one-third right lobe, with solid cell nests (SCNs) adjacent to the MTC. C-cells were scattered mainly around the SCNs, but C-cell hyperplasia was not evident in the background thyroid. The MTC cell phenotype was immunohistochemically identical to background C-cells, but was completely different from the SCN main cells. Direct DNA analyses of isolated MTC paraffin-embedded specimens revealed two RET proto-oncogene missense point mutations in exon 11 (i.e., C630R and C634W). The non-tumor thyroid tissue did not reveal any mutations. This study reports the smallest case of sporadic MTC with a double RET somatic mutation, substantiating that RET mutations can occur during a very early stage of carcinogenesis. The combined presence of C630R and C634W represent a novel somatic mutation in sporadic MTC. The present case indicates that the sporadic MTC originated from the surrounding C-cells of the SCNs without C-cell hyperplasia and that the SCN main cells may not be able to develop into an MTC. © 2017 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

  19. Colonic neuroendocrine carcinoma in a child

    International Nuclear Information System (INIS)

    Sasi, Omai Al; Rifai, Ayman; Hugosson, Claes; Sathiapalan, Rajeev; Kofide, Amani; Tulbah, Asthma Mahmoud Mohamed; Al-Mehaidib, Ali

    2005-01-01

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

  20. Are there tumor suppressor genes on chromosome 4p in sporadic colorectal carcinoma?

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    Zheng, Hai-Tao; Jiang, Li-Xin; Lv, Zhong-Chuan; Li, Da-Peng; Zhou, Chong-Zhi; Gao, Jian-Jun; He, Lin; Peng, Zhi-Hai

    2008-01-07

    To study the candidate tumor suppressor genes (TSG) on chromosome 4p by detecting the high frequency of loss of heterozygosity (LOH) in sporadic colorectal carcinoma in Chinese patients. Seven fluorescent labeled polymorphic microsatellite markers were analyzed in 83 cases of colorectal carcinoma and matched normal tissue DNA by PCR. PCR products were electrophoresed on an ABI 377 DNA sequencer. Genescan 3.7 and Genotype 3.7 software were used for LOH scanning and analysis. The same procedure was performed by the other six microsatellite markers spanning D4S3013 locus to make further detailed deletion mapping. Comparison between LOH frequency and clinicopathological factors was performed by c2 test. Data were collected from all informative loci. The average LOH frequency on 4p was 24.25%, and 42.3% and 35.62% on D4S405 and D4S3013 locus, respectively. Adjacent markers of D4S3013 displayed a low LOH frequency (4p15.2) and D4S405 (4p14) locus are detected. Candidate TSG, which is involved in carcinogenesis and progression of sporadic colorectal carcinoma on chromosome 4p, may be located between D4S3017 and D4S2933 (about 1.7 cm).

  1. Correlation of RET somatic mutations with clinicopathological features in sporadic medullary thyroid carcinomas

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    Moura, M M; Cavaco, B M; Pinto, A E; Domingues, R; Santos, J R; Cid, M O; Bugalho, M J; Leite, V

    2009-01-01

    Screening of REarranged during Transfection (RET) gene mutations has been carried out in different series of sporadic medullary thyroid carcinomas (MTC). RET-positive tumours seem to be associated to a worse clinical outcome. However, the correlation between the type of RET mutation and the patients' clinicopathological data has not been evaluated yet. We analysed RET exons 5, 8, 10–16 in fifty-one sporadic MTC, and found somatic mutations in thirty-three (64.7%) tumours. Among the RET-positive cases, exon 16 was the most frequently affected (60.6%). Two novel somatic mutations (Cys630Gly, c.1881del18) were identified. MTC patients were divided into three groups: group 1, with mutations in RET exons 15 and 16; group 2, with other RET mutations; group 3, having no RET mutations. Group 1 had higher prevalence (P=0.0051) and number of lymph node metastases (P=0.0017), and presented more often multifocal tumours (P=0.037) and persistent disease at last control (P=0.0242) than group 2. Detectable serum calcitonin levels at last screening (P=0.0119) and stage IV disease (P=0.0145) were more frequent in group 1, than in the other groups. Our results suggest that, among the sporadic MTC, cases with RET mutations in exons 15 and 16 are associated with the worst prognosis. Cases with other RET mutations have the most indolent course, and those with no RET mutations have an intermediate risk. PMID:19401695

  2. Challenge in diagnosis and treatment of colonic carcinoma ...

    African Journals Online (AJOL)

    Alaa Hussein Abdel-Razek

    2012-01-23

    Jan 23, 2012 ... Colon carcinoma;. Colonic emergency;. Cancer challenge;. Colectomy. Abstract Introduction: Despite advances in perioperative care and operative techniques, urgent ... consent was signed for colectomy and intestinal stoma to be able to deal with different conditions. The emergency surgical procedures ...

  3. Detection of secondary involvement of the colon from gastric carcinoma

    International Nuclear Information System (INIS)

    Miyakawa, Kunihisa

    1994-01-01

    A comparative study with CT and barium enema (BE) was performed on 60 patients (121 lesions) with secondary involvement to the colon from gastric carcinoma. The lesions were visualized as abnormally thick colonic walls (more than 5 mm in thickness) on CT as well as stenotic or striped appearance on BE. The colonic lesions were equally detected by CT and BE in 49 patients (103 lesions). Although CT was superior to BE in only one patient (one lesion), BE was more accurated in 10 patients (17 lesions). CT failed to demonstrate early changes of secondary involvement to the colon. The presence of ascites or mesenteric abnormalities was not detected by CT in 15 patients, even though spread of gastric carcinoma to the colon mainly occurred by the direct invasion along mesenteric reflections or intraperitoneal seeding. As a conclusion, it was found that BE was more accurate for the detection of secondary involvement to the colon from gastric carcinoma comparing to CT. Normal findings on CT did not eliminate the possibility of colonic metastasis, therefore, BE study was desirable if clinical findings suggest the involvement of colonic metastasis. (author)

  4. Colonic carcinoma with multiple small bowel perforations mimicking intestinal obstruction

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    Khanna Rahul

    2006-09-01

    Full Text Available Abstract Background Carcinoma of the colon may present with perforation proximal to the site of malignancy. Caecum is the commonest site of perforation if the ileocecal valve is patent and the jejunal and ileal perforations are very rare. Case presentation A 35 year male presented with intestinal obstruction. Emergency laparotomy revealed carcinoma of the transverse colon with multiple pinpoint perforations along antimesenteric border of ileum, which were wrapped with omentum, and no peritoneal contamination was present. Extended right hemicolectomy with jejunocolic anastomosis was done. Patient made uneventful recovery in postoperative period and was treated with adjuvant chemotherapy. Conclusion Patients with colonic carcinoma and incompetent ileocecal valve may present with intestinal perforation. Increased intraluminal pressure and closed loop obstruction may lead to ischemia and perforation of the small bowel.

  5. Ischaemic colitis associated with carcinoma of the colon

    International Nuclear Information System (INIS)

    Reeders, J.W.A.; Rosenbusch, B.; Tytgat, G.N.J.

    1982-01-01

    In a retrospective study of one hundred and seventy patients with ischaemic colitis, we found eight patients with partially obstructive carcinoma of the colon located distally, seven located in the sigmoid and one in the splenic flexure. The frequency of this association (1-4.7% in the literature and 5.3% in our series) requires careful examination by radiologist and surgeon. The radiologist should be alert to the association of ischaemic damage proximal to an obstructive colorectal cancer. The surgeon must examine any colonic segment removed for carcinoma in order to exclude an ischaemic process in the area of the anastomosis and prevent leakage at the anastomosis or stricture formation. (orig.)

  6. Colonic metastasis from renal cell carcinoma: helical-CT demonstration

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    Diaz-Candamio, M.J.; Pombo, S.; Pombo, F.

    2000-01-01

    Clinically evident colonic metastasis from renal cell carcinoma (RCC) is rare. In the present study a hypervascular sigmoid mass was demonstrated on arterial-phase helical CT using a water enema in a patient who had suffered left nephrectomy 8 years previously for RCC. The intense and early enhancement of the lesion suggested the possibility of a solitary colonic metastasis from RCC, a diagnosis which was pathologically confirmed. (orig.)

  7. High prevalence of exon 8 G533C mutation in apparently sporadic medullary thyroid carcinoma in Greece.

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    Sarika, H L; Papathoma, A; Garofalaki, M; Vasileiou, V; Vlassopoulou, B; Anastasiou, E; Alevizaki, M

    2012-12-01

    Genetic screening for ret mutation has become routine practice in the evaluation of medullary thyroid carcinoma (MTC). Approximately 25% of these tumours are familial, and they occur as components of the multiple endocrine neoplasia type 2 syndromes (MEN 2A and 2B) or familial MTC. In familial cases, the majority of mutations are found in exons 10, 11, 13, 14 or 15 of the ret gene. A rare mutation involving exon 8 (G533C) has recently been reported in familial cases of MTC in Brazil and Greece; some of these cases were originally thought to be sporadic. The aim of this study was to re-evaluate a series of sporadic cases of MTC, with negative family history, and screen them for germline mutations in exon 8. Genomic DNA was extracted from peripheral lymphocytes in 129 unrelated individuals who had previously been characterized as 'sporadic' based on the negative family history and negative screening for ret gene mutations. Samples were analysed in Applied Biosystems 7500 real-time PCR and confirmed by sequencing. The G533C exon 8 mutation was identified in 10 of 129 patients with sporadic MTC. Asymptomatic gene carriers were subsequently identified in other family members. In our study, we found that 7·75% patients with apparently sporadic MTC do carry G533C mutation involving exon 8 of ret. We feel that there is now a need to include exon 8 mutation screening in all patients diagnosed as sporadic MTC, in Greece. © 2012 Blackwell Publishing Ltd.

  8. The review of 134 cases colon and rectal carcinoma

    International Nuclear Information System (INIS)

    Kim, Chung Kyu; Choi, Byung Sook

    1971-01-01

    Barium Enema study for colon examination is of great importance in the health care of our people and its value can be increased by a wide understanding of the attendant difficulties and limitation. Since the incidence of the colon and rectal carcinoma is increasing, the barium enema examination is more valuable. Radiologically diagnosed 134 cases of colon and rectal carcinoma from January 1964 to June 1970 have been reviewed at Yensei Univ., College of Medicine. Among the total admission during these years, the ratio of the colon and rectal carcinoma was 0.29 percent, and the incidence among barium enema examination was 5.3%. The peak age range was between 40 and 50 years. The average age of the patients was 46 years. It was more common in male. The clinical picture was rather vague in some cases, especially in the lesions of right colon. The large number of cases has bowel habit change, tarry or bloody stool and abdominal pain. About 60% of the lesions were located in rectum and 40% was proximal portion from the rectum, which could not be completely diagnosed only by digital examination and proctosigmoidoscopy. On roentgenogram, the most common form was encircling type, next was fungating. The positivity for accuracy of the barium enema examination was 90%. Majority of cancers of the colon, particularly those that produce symptoms are relative gross lesions. In daily practise we have to eager to find out small lesions by repeat and complete barium enema examination, including double contrast study. Early diagnosis is an aid immediate, logical objective in attempts to decrease the morbidity and mortality from carcinoma of colon

  9. Challenge in diagnosis and treatment of colonic carcinoma ...

    African Journals Online (AJOL)

    Introduction: Despite advances in perioperative care and operative techniques, urgent colorectal operations are still associated with higher mortality and morbidity than elective surgery. Aim: This study was to identify the challenge in diagnosis and treatment of emergencies caused by colon carcinoma; and to assess its ...

  10. Carcinoma of the colon: Diagnosis by ultrasound and enema

    International Nuclear Information System (INIS)

    Cremin, B.J.; Brown, R.A.

    1987-01-01

    Carcinoma of the colon presenting before puberty is rare and few cases have been recorded in radiological literature. The symptomatology is usually vague but may be similar to the classical presentation of adults. The barium enema will also show the same constricting lesions. Two cases are reported, in one of which the initial diagnosis was made by ultrasound. (orig.)

  11. The survival of patients with Stage III Colon Cancer is improved in HNPCC compared with sporadic cases. A Danish registry based study

    DEFF Research Database (Denmark)

    Brixen, Line Merrild; Bernstein, Inge Thomsen; Bülow, Steffen

    2013-01-01

    AIM: Patients with hereditary non-polyposis colorectal cancer (HNPCC) seem to have a better prognosis than those with sporadic colon cancer (CC)s. The aim was to compare survival after stage III CC in patients with HNPCC with those having sporadic CC. METHOD: 230 patients with hereditary cancer...... history of cancer. Patient characteristics, geographic differences and survival data were analyzed. RESULTS: The overall survival (OS) was better in HNPCC patients compared to sporadic CC after stratification for sex and age (p=0.02; CI 1.04-1.7). The 5-year survival was 70% in HNPCC patients compared...... from The Danish HNPCC-Register and 3557 patients with sporadic CC from The Danish Colorectal Cancer Database, diagnosed during May 2001-December 2008 were included. HNPCC patients were classified according to Mismatch Repair mutation status and family pedigree. Sporadic cases had no known family...

  12. Xanthogranulomatous Colitis masquerading as carcinoma of colon

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    Akhil Kapoor

    2015-01-01

    Full Text Available Xanthogranulomatous inflammation (XGI is an uncommon pathological diagnosis involving various organ systems, the most common being the gall bladder and kidney. It can masquerade as a malignant mass thus, requiring a clinical suspicion for accurate and timely diagnosis. A 65-year-old woman presented with acute onset of obstipation and vomiting suggesting acute obstruction. Contrast enhanced computed tomography of abdomen revealed a solid irregular mass in the ascending colon with large necrotic areas and surrounding enlarged nodes suggestive of malignancy arising from right colon. Right hemi-colectomy was performed. Histopathology of the surgical specimen showed florid inflammatory infiltrate with collection of histiocytes, lymphocytes and polymorphs. Further immunohistochemistry was conducted, and CD68 and CD45 were found to be positive and pan-cytokeratin was negative. A clinico-pathological diagnosis was thus established to be xanthogranulomatous colitis.

  13. A cohort study on 10-year survival of sporadic medullary thyroid carcinoma with somatic RET mutation

    Directory of Open Access Journals (Sweden)

    Li-Lun Chuang

    2016-11-01

    Full Text Available Somatic rearranged during transfection (RET mutations are reported in 40–50% of sporadic medullary thyroid carcinoma (sMTC patients with prognostic significance. As there is a lack of somatic RET mutations reported previously for the Taiwanese population, we tried to assess the presence of somatic RET mutations and evaluate the potential outcome predictors for our sMTC patients. We collected data from seven sMTC patients from the years 1997 to 2005 and analyzed their clinic-pathological features up to 2015. All patients were still alive to follow up for 11∼18 years. Tumor DNAs were extracted to assess exons 10–11 and 13–16, and the intron-exon boundaries of the RET gene. Six cases (86% were screened positive of somatic RET gene mutations in hotspot regions, one at M918T, one at C620R, and three at C634S, with another two rare mutations at L629Q and V642I. Comparing the current tumor, node, metastases staging system, the 10-year survival outcomes for our sMTC patients was not predicted by serum calcitonin and/or carcinoembryonic antigen, surgical extent, and presence of the somatic RET gene mutations. The small cohort demonstrated a relatively good outcome of sMTC patients to survive >10 years. In addition, intensive treatment with total thyroidectomy with extensive neck lymph node dissection seemed to be the critical determinant of better survival outcome for sMTC patients.

  14. [A case of mixed adenoneuroendocrine carcinoma of the transverse colon].

    Science.gov (United States)

    Kusakabe, Jiro; Miki, Akira; Kobayashi, Hiroyuki; Uryuhara, Kenji; Hashida, Hiroki; Mizumoto, Masaki; Kaihara, Satoshi; Hosotani, Ryo; Yamashita, Daisuke

    2014-11-01

    A 7 1-year-old man presented to our hospital with constipation and abdominal pain. Computed tomography of the abdomen and colonoscopy revealed advanced cancer of the transverse colon. The biopsy specimen indicated a highly differentiated adenocarcinoma. The patient underwent extended right hemicolectomy with regional lymph node dissection. Pathological examination showed a neuroendocrine carcinoma (NEC) with concurrent adenocarcinoma of the transverse colon and regional lymph node metastases of the NEC and adenocarcinoma. The histopathological examination confirmed a diagnosis of mixed adenoneuroendocrine carcinoma (MANEC) in accordance with the 2010 WHO Classification of Tumors of the Digestive System. Liver and lung metastases were identified 8 months after the surgery. We administered chemotherapy including 5-fluorouracil, Leucovorin, and oxaliplatin (mFOLFOX) plus bevacizumab, with limited therapeutic effect, as the disease progressed despite treatment. The patient chose best supportive care 13 months after the surgery. Several studies have reported that most patients with adenoendocrine cell carcinoma, including MANEC, experience relapse within 1 year after surgery, and few patients remain disease-free for long periods after surgery. The optimal strategy for the management of MANEC is variable owing to its rarity; only 2 cases of MANEC in the colon, including the present case, have been reported in Japan. It is thus important to gather more evidence on this disease and its management.

  15. The CT diagnostic value of emergency intestinal obstruction caused by colon carcinoma

    International Nuclear Information System (INIS)

    Li Zhuohong

    2008-01-01

    Objective: To analyze the value of CT in the diagnosis of emergency intestinal obstruction (EIOB) caused by colon carcinoma. Methods: 17 cases with EIOB caused by colon carcinoma were submitted to CT scanning. Contrast enhanced scans were performed in 11 cases. The locations and characters of EIOB in CT imaging were recorded and compared with operation results. Results: The locations of the obstructions were 3 cases in cecum, 1 in ascending colon, 1 in transverse colon, 2 in descending colon, and 10 in sigmoid colon. Compared with operation results, the accuracy of CT in locating obstruction was 94%, and in qualitative diagnosis of colon carcinomas was 70%. Conclusion: CT can display very well the obstruction location of EIOB, and It has certain value in character izing colon carcinoma with EIOB. (authors)

  16. Integral analysis of p53 and its value as prognostic factor in sporadic colon cancer

    International Nuclear Information System (INIS)

    Fariña Sarasqueta, Arantza; Morreau, Hans; Forte, Giusi; Corver, Wim E; Miranda, Noel F de; Ruano, Dina; Eijk, Ronald van; Oosting, Jan; Tollenaar, Rob AEM; Wezel, Tom van

    2013-01-01

    p53 (encoded by TP53) is involved in DNA damage repair, cell cycle regulation, apoptosis, aging and cellular senescence. TP53 is mutated in around 50% of human cancers. Nevertheless, the consequences of p53 inactivation in colon cancer outcome remain unclear. Recently, a new role of p53 together with CSNK1A1 in colon cancer invasiveness has been described in mice. By combining data on different levels of p53 inactivation, we aimed to predict p53 functionality and to determine its effects on colon cancer outcome. Moreover, survival effects of CSNK1A1 together with p53 were also studied. Eighty-three formalin fixed paraffin embedded colon tumors were enriched for tumor cells using flow sorting, the extracted DNA was used in a custom SNP array to determine chr17p13-11 allelic state; p53 immunostaining, TP53 exons 5, 6, 7 and 8 mutations were determined in combination with mRNA expression analysis on frozen tissue. Patients with a predicted functional p53 had a better prognosis than patients with non functional p53 (Log Rank p=0.009). Expression of CSNK1A1 modified p53 survival effects. Patients with low CSNK1A1 expression and non-functional p53 had a very poor survival both in the univariate (Log Rank p<0.001) and in the multivariate survival analysis (HR=4.74 95% CI 1.45 – 15.3 p=0.009). The combination of mutational, genomic, protein and downstream transcriptional activity data predicted p53 functionality which is shown to have a prognostic effect on colon cancer patients. This effect was specifically modified by CSKN1A1 expression

  17. Association between cigarette smoking, APC mutations and the risk of developing sporadic colorectal adenomas and carcinomas

    International Nuclear Information System (INIS)

    Sæbø, Mona; Skjelbred, Camilla F; Breistein, Rebecca; Lothe, Inger Marie B; Hagen, Per Chr; Bock, Gunter; Hansteen, Inger-Lise; Kure, Elin H

    2006-01-01

    The association between colorectal cancer (CRC) and smoking has not been consistent. Incomplete smoking history and association to a specific subset of CRC tumors have been proposed as explanations. The adenomatous polyposis coli (APC) gene has been reported to have a 'gatekeeper' function in the colonic mucosa. To evaluate the hypothesis that cigarette smoking is associated with adenoma and carcinoma development and further to investigate whether this association is due to mutations in the APC gene, we used a study population consisting of 133 cases (45 adenomas and 88 carcinomas) and 334 controls. All tumors were sequenced in the mutation cluster region (MCR) of the APC gene. Cases and controls were drawn from a homogeneous cohort of Norwegian origin. The mutational spectra of the APC gene revealed no difference in frequencies of mutations in cases based on ever and never smoking status. An overall case-control association was detected for adenomas and 'ever smoking' OR = 1.73 (95% CI 0.83–3.58). For CRC cases several smoking parameters for dose and duration were used. We detected an association for all smoking parameters and 'duration of smoking > 30 years', yielded a statistically significant OR = 2.86 (1.06–7.7). When cases were divided based on APC truncation mutation status, an association was detected in adenomas without APC mutation in relation to 'ever smoking', with an OR = 3.97 (1.26–12.51). For CRC cases without APC mutation 'duration of smoking > 30 years', yielded a statistically significant OR = 4.06 (1.20–13.7). The smoking parameter 'starting smoking ≥ 40 years ago' was only associated with CRC cases with APC mutations, OR = 2.0 (0.34–11.95). A case-case comparison revealed similar findings for this parameter, OR = 2.24 (0.73–6.86). Our data suggest an association between smoking and adenoma and CRC development. This association was strongest for cases without APC truncation

  18. Diagnostic microRNA markers to screen for sporadic human colon cancer in blood.

    Science.gov (United States)

    Ahmed, Farid E; Amed, Nancy C; Vos, Paul W; Bonnerup, Chris; Atkins, James N; Casey, Michelle; Nuovo, Gerard J; Naziri, Wade; Wiley, John E; Allison, Ron R

    2012-01-01

    We carried out this study to present proof-of-principal application, showing that by using a global microarray expression analysis, followed by quantitative stem-loop reverse transcriptase in conjunction with TaqMan® polymerase chain reaction (PCR) analysis of micro(mi)RNA genes, on limited number of plasma and tissue samples obtained from 20 individuals (five healthy, five TNM stage 0-1 colon cancer, five stage 2 and five stage 3), we were able to quantitatively monitor miRNA changes at the various TNM stages of colon cancer progression, particularly at the early, pre-malignant adenoma stage (e.g. polyps ≥ 1 cm with high grade dysplasia). The expression of some of the tested miRNAs showed less variability in tissue than in plasma. Nevertheless, our limited preliminary data on the plasma by itself show that plasma is well-suited for screening, and that the quantitative changes in the expression of a few cell-free circulatory mature miRNA molecules in plasma, that are associated with colon cancer progression, would provide for more sensitive and specific markers than those tests currently available on the market. In addition, analysis of miRNA molecules offers a quantitative and cost-effective non-invasive diagnostic approach for screening, than currently employed methods in a prevalent cancer that can be cured if it is detected at the early TNM stages, and that becomes deadly if not diagnosed before metastasis. Thus, a larger prospective and properly randomized clinical study using plasma derived from many control individuals and at various stages of colon cancer (TNM stages 0-IV) from patients, in order to corroborate the initial results, is now urgently needed in order to allow for a statistically valid analysis, standardizing test conditions which will provide a means for determining the true sensitivity and specificity of a miRNA-screening approach. This approach, when combined with bioinformatics analysis to correlate miRNA seed data with mRNA target data

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

    Directory of Open Access Journals (Sweden)

    A. B. Villert

    2016-01-01

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

  20. Protruding and non-protruding colon carcinomas originating in gut-associated lymphoid tissue.

    Science.gov (United States)

    Rubio, Carlos A; Lindh, Claes; Björk, Jan; Törnblom, Hans; Befrits, Ragnar

    2010-07-01

    Colon carcinomas arising in gut-associated lymphoid tissue (GALTC) are termed dome carcinomas (DC) because of their protruding phenotype. Only 8 GALTC cases have been reported in the literature. A female patient, aged 53, having a familial pedigree of colon cancer, uterine cervix cancer and brain tumour developed a signet-ring carcinoma in the cecum and 10 years later endometrial cancer. While asymptomatic, a plaque-like protrusion in the colon was detected at surveillance colonoscopy. Histology demonstrated a protruding GALTC. The surgical specimen showed four additional carcinomas: 2 GALTC (non-protruding) and 2 carcinomas in lymphoid-free colonic mucosa (LFCMC). Since adenomas could not be demonstrated neither previously nor in the colectomy specimen, it is suggested that the GALTCs in this patient may have followed the GALT-carcinoma pathway.

  1. Caecal amebic colitis mimicking obstructing right sided colonic carcinoma with liver metastases: A rare case

    Directory of Open Access Journals (Sweden)

    Nikhil Moorchung

    2014-01-01

    Full Text Available Intestinal Entamoeba Histolytica infection can lead to colitis, abscess formation, colonic perforation and rarely amoeboma. We report a case of colonic amoebiasis, in which the presenting symptoms and radiological findings closely resembled an obstructing right-sided colonic carcinoma, with liver metastases.

  2. Gastric Medullary Carcinoma with Sporadic Mismatch Repair Deficiency and a TP53 R273C Mutation: An Unusual Case with Wild-Type BRAF

    Directory of Open Access Journals (Sweden)

    Brett M. Lowenthal

    2017-01-01

    Full Text Available Medullary carcinoma has long been recognized as a subtype of colorectal cancer associated with microsatellite instability and Lynch syndrome. Gastric medullary carcinoma is a very rare neoplasm. We report a 67-year-old male who presented with a solitary gastric mass. Total gastrectomy revealed a well-demarcated, poorly differentiated carcinoma with an organoid growth pattern, pushing borders, and abundant peritumoral lymphocytic response. The prior cytology was cellular with immunohistochemical panel consistent with upper gastrointestinal/pancreaticobiliary origin. Overall, the histopathologic findings were consistent with gastric medullary carcinoma. A mismatch repair panel revealed a mismatch repair protein deficient tumor with loss of MLH1 and PMS2 expression. BRAF V600E immunostain (VE1 and BRAF molecular testing were negative, indicating a wild-type gene. Tumor sequencing of MLH1 demonstrated a wild-type gene, while our molecular panel identified TP53 c.817C>T (p.R273C mutation. These findings were compatible with a sporadic tumor. Given that morphologically identical medullary tumors often occur in Lynch syndrome, it is possible that mismatch repair loss is an early event in sporadic tumors with p53 mutation being a late event. Despite having wild-type BRAF, this tumor is sporadic and unrelated to Lynch syndrome. This case report demonstrates that coordinate ancillary studies are needed to resolve sporadic versus hereditary rare tumors.

  3. Somatic mutations in mismatch repair genes in sporadic gastric carcinomas are not a cause but a consequence of the mutator phenotype

    NARCIS (Netherlands)

    Pinto, Mafalda; Wub, Ying; Mensink, Rob G. J.; Cirnes, Luis; Seruca, Raquel; Hofstra, Robert M. W.

    2008-01-01

    In hereditary nonpolyposis colorectal cancer (HNPCC), patients' mismatch repair (MMR) gene mutations cause MMR deficiency, leading to microsatellite instability (MSI-H). MSI-H is also found in a substantial fraction of sporadic gastric carcinomas (SGC), mainly due to MLH1 promoter hypermethylation,

  4. Endometriosis presenting as carcinoma colon in a perimenopausal woman

    Directory of Open Access Journals (Sweden)

    Tanuja Muthyala

    2015-01-01

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

  5. N-acetyl transferase 2/environmental factors and their association as a modulating risk factor for sporadic colon and rectal cancer.

    Science.gov (United States)

    Procopciuc, Lucia M; Osian, Gelu; Iancu, Mihaela

    2017-09-01

    The aim of this study was to evaluate the association between environmental factors and colon or rectal cancer after adjusting for N-acetyl transferase 2 (NAT2) phenotypes. Ninety-six patients with sporadic colon cancer, 54 with sporadic rectal cancer and 162 control subjects were genotyped for NAT2-T341C, G590A, G857A, A845C, and C481T using sequencing and PCR-RFLP analysis. The risk for colon cancer was increased in carriers of the homozygous negative genotypes for NAT2*5C-T341C, NAT2*6B-G590A, NAT2*7B-G857A, NAT2*18-A845C, and NAT2*5A-C481T. The risk for rectal cancer was increased in carriers of the homozygous negative genotypes for NAT2*5C-T341C, NAT2*7B-G857A, and NAT2*5A-C481T. High fried red meat intake associated with NAT2-T341C, G590A, G857A, A845C, and C481T rapid acetylator allele determines a risk of 2.39 (P=.002), 2.39 (P=.002), 2.37 (P=.002), 2.28 (P=.004), and 2.51 (P=.001), respectively, for colon cancer, whereas in the case of rectal cancer, the risk increased to 7.55 (Pcolon cancer, whereas the risk for rectal cancer is 9.72 (Pcolon cancer. Fried red meat, alcohol, and smoking increase the risk of sporadic CRC, especially of colon cancer, in the case of rapid acetylators for the NAT2 variants. © 2016 Wiley Periodicals, Inc.

  6. Loss of HLA class I and mismatch repair protein expression in sporadic endometrioid endometrial carcinomas

    NARCIS (Netherlands)

    de Jong, Renske A.; Boerma, A.; Boezen, H.M.; Mourits, M.J.E.; Hollema, H.; Nijman, H.W.

    2012-01-01

    Tumor cells can escape from cytotoxic T-cell responses by downregulation of human leukocyte antigen (HLA) class I molecules expressed at the cell surface which has been associated with a deficient mismatch repair (MMR) system in colorectal carcinomas. Our study investigated the association between

  7. Colon cancer

    Science.gov (United States)

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

  8. Immunohistochemical detection for nuclear beta-catenin in sporadic basal cell carcinoma.

    Science.gov (United States)

    Yamazaki, F; Aragane, Y; Kawada, A; Tezuka, T

    2001-11-01

    Despite the increasing incidence of basal cell carcinoma (BCC), its pathogenesis has remained largely unknown. Recently, it was reported that genes involved in tissue morphogenesis, such as sonic hedgehog or patched, were found to be mutated in BCC, suggesting the involvement of those molecules in the pathogenesis of this tumour. Furthermore, there is evidence that the Wnt-mediated signalling pathway may be one of the downstream targets of sonic hedgehog-mediated signalling, which has led us to focus on molecular events on the Wnt pathway in BCC. Among the signal transducers involved in the Wnt pathway, it is clear that beta-catenin plays a pivotal role in the promotion of morphogenesis and cell growth. In respect to this, it has been reported that, in particular circumstances, as in colorectal cancers, beta-catenin migrates to the nuclei, where it exerts an ability to activate the transcription of various genes. To investigate the cellular distribution of beta-catenin in skin tumours, in particular, in BCC. Twenty skin biopsy specimens derived from BCC, 10 from inflammatory skin diseases and five from squamous cell carcinomas were immunostained with an antibody directed against beta-catenin. Fourteen of the 20 BCC samples tested showed nuclear localization of beta-catenin, while none of the other samples gave rise to positive nuclear staining. Nuclear localization of beta-catenin is a characteristic feature of BCC; this suggests its tumorigenic role in this tumour. This gives us a further insight into the molecular pathogenesis of BCC.

  9. Mutations of codon 918 in the RET proto-oncogene correlate to poor prognosis in sporadic medullary thyroid carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Zedenius, J.; Svensson, A.; Baeckdahl, M.; Wallin, G. [Karolinska Hospital, Stockholm (Sweden)] [and others

    1995-10-01

    The hereditary multiple endocrine neoplasia syndromes types 2A and B (MEN 2A and B) were recently linked to germline mutations in the RET proto-oncogene, altering one of five cysteine residues in exon 10 or 11 (MEN 2A), or substituting a methionine for a threonine at codon 918 in exon 16 (MEN 2B). The latter mutation also occurs somatically in some sporadic medullary thyroid carcinomas (MTC), and has in a previous study been correlated with a less favorable clinical outcome. In the present study, 46 MTCs were selected for investigation of the codon 918 mutation. The mutation was found in 29 tumors (63%), and was significantly correlated with a poor outcome, with regard to distant metastasis or tumor recurrence (p<10{sup 4}). Two tumors showed multifocal growth and C-cell hyperplasia, and these patients were therefore also investigated for germline mutations in exons 10, 11 and 16. The codon 918 mutation was found only in the tumors, thus of somatic origin. The RET codon 918 mutation may have prognostic impact, and therefore preoperative assessment may influence decision-making in the treatment of patients suffering from MTC. 13 refs., 1 fig., 1 tab.

  10. Sporadic ret-rearranged papillary carcinoma of the thyroid: a subset of slow growing, less aggressive thyroid neoplasms?

    Science.gov (United States)

    Soares, P; Fonseca, E; Wynford-Thomas, D; Sobrinho-Simões, M

    1998-05-01

    Despite the large amount of information accumulated on the role played by ret activation in the oncogenesis of papillary thyroid carcinoma (PTC), the biological and clinical significance of such activation 'in vivo' remains controversial. The aim of this study was to address some of the existing controversies by comparing two groups of unselected PTCs, one with and the other without ret rearrangement, with regard to several clinicopathological and biological features. Thirty-three PTCs were selected at random. ret rearrangement was found in eight cases (24.2 per cent) using Southern blot analysis. The mean age of the patients with tumours displaying ret rearrangement (28 +/- 3.1 years) was significantly lower than that of the patients harbouring cases that did not present rearrangement (45 +/- 2.9 years). The large majority of the tumours with ret rearrangement displayed a papillary or mixed follicular-papillary pattern and very low proliferative activity. ret rearrangement correlated significantly with decreased cytoplasmic expression of E-cadherin. No significant differences were found regarding the gender of the patients, tumour size, multicentricity, extrathyroidal growth, vascular invasion, lymphocytic infiltration, lymph node involvement or the expression of E-cadherin (membrane), c-erb-B2, c-met, Bcl-2, and vimentin. It is proposed that sporadic PTCs harbouring a ret rearrangement occur frequently as slow growing, papillary, or predominantly papillary tumours that do not usually progress towards less differentiated neoplasms representing what might be described as a Bonsai phenotype.

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

    Directory of Open Access Journals (Sweden)

    Chung-Cheng Lin

    2013-10-01

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

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

    OpenAIRE

    Ihab Shafek Atta; Fahd Nasser AlQahtani

    2016-01-01

    We are presenting a case associated with papillary thyroid carcinoma, renal cell carcinoma, invasive mammary carcinoma, chondrosarcoma, benign ganglioneuroma, and numerous colon adenomas. The patient had a family history of colon cancer, kidney and bladder cancers, lung cancer, thyroid cancer, leukemia, and throat and mouth cancers. She was diagnosed with colonic villous adenoma at the age of 41 followed by thyroid, renal, and breast cancers and chondrosarcoma at the ages of 48, 64, 71, and 7...

  13. Radioimmunoassay of carcinoembryonic antigen in serum of normal subjects and patients with colonic carcinoma 1

    Science.gov (United States)

    Kleinman, Martin S.; Turner, Michael D.

    1972-01-01

    Sera from 14 normal subjects and 43 patients with colonic carcinoma were evaluated for the presence of carcinoembryonic antigen (CEA). Inhibiting material which behaved in the assay in a similar manner to CEA was found in normal serum at concentrations below 2·8 ng/ml. Its nature has not so far been established. Thirty-eight of the 43 patients with colonic carcinoma showed levels of serum CEA in excess of 2·8 ng/ml. The concentration of CEA in serum was correlated with the extent of the disease as classified by a staging procedure similar to that of Dukes (1932). Examination of a small number of specimens of colonic carcinoma and normal colonic mucosa suggested that the concentration of CEA in different adenocarcinomata may vary, and that traces of cross-reacting material may be found in some normal mucosae. PMID:4338549

  14. Low RAP80 mRNA expression correlates with shorter survival in sporadic high-grade serous ovarian carcinoma.

    Science.gov (United States)

    Romeo, Margarita; Karachaliou, Niki; Chaid, Imane; Queralt, Cristina; De Aguirre, Itziar; Del Carmen Gómez, María; Sanchez-Ronco, María; Radua, Joaquim; Ramírez, José Luís; Rosell, Rafael

    2017-03-02

    Homologous recombination (HR) is frequently impaired in sporadic high-grade serous ovarian carcinoma (sHGSOC) due to deficiencies in BRCA1/2 genes, a situation associated with hypersensitivity to platinum compounds. Alterations in other genes can also cause HR deficiency. Preclinical data show that RAP80 is an HR-pathway-related gene that influences BRCA1 activity. RAP80 has been reported to affect outcome in some solid neoplasms. This study investigates the role of RAP80 in sHGSOC survival. mRNA expression of RAP80 was analyzed in tumor samples from 35 patients who postoperatively received standard platinum-based chemotherapy. The effects of RAP80 expression on progression-free survival (PFS) and overall survival (OS) were examined by means of Cox regressions. The clinical variables known to have prognostic value (FIGO stage, residual disease at surgery, and debulking surgery) were included as covariates in the analysis. BRCA1 was analyzed given the moderate correlations with RAP80. Median follow-up, PFS and OS were 61.3, 20.2 and 62.8 months, respectively. Low RAP80 expression levels were associated with shorter PFS (HR = 1.449, p = 0.007) and OS (HR = 1.331, p = 0.047). This is the first study to show a potential prognostic role of RAP80 expression in patients with HGSOC. The results suggest that HR deficiency due to low RAP80 expression is not associated with hypersensitivity to platinum compounds in sHGSOC.

  15. Somatic mutations of the ret Protooncogene in sporadic medullary thyroid carcinoma are not restricted to exon 16 and are associated with tumor recurrence

    Energy Technology Data Exchange (ETDEWEB)

    Romei, C.; Elisei, R.; Pinchera, A. [Univ. of Pisa (Italy)] [and others

    1996-04-01

    Germline point mutations in exons 10, 11, and 16 of the ret protooncogene have been identified as causative in multiple endocrine neoplasia type 2 and in familial medullary thyroid carcinoma (MTC). Somatic point mutations of the same gene, exclusively associated with codon 918 of exon 16, have also been reported in few cases of sporadic medullary thyroid carcinoma. We analyzed the blood and tumor DNA of 19 patients with sporadic MTC and 6 patients with primary parathyroid adenoma for point mutations at exons 10, 11, and 16 of the ret protooncogene by restriction analysis of the PCR-amplified product and by sequence analysis of exons 10 and 11. A Cys{sup 634}{r_arrow}Tyr mutation was found in both the tumoral and blood DNA of one patient, indicating that he was affected by an hereditary form of MTC, erroneously considered sporadic. In the other 18 patients with MTC, somatic point mutations of ret were found in 8 cases (44.4%). In 5 cases the mutation affected exon 16 (Met{sup 918}{r_arrow}Thr), and in 3 cases it affected exon 11 (Cys{sup 634}{r_arrow}Arg in 1 and Cys{sup 634}{r_arrow}Trp in 2); these 3 mutations were confirmed by sequence analysis. The remaining 10 patients had no mutation in exon 10 by either restriction analysis or sequence analysis. Clinical data showed that 75% of the patients whose tumor carried ret mutation had tumor recurrence and/or increased serum calcitonin concentrations during the postsurgical follow-up period as opposed to 10% of the patients without mutations (P < 0.02, by {chi}{sup 2} analysis). No ret mutation was found in the tumoral DNA from parathyroid adenomas. Our findings indicate that the somatic ret point mutation frequently found in sporadic MTC may affect not only exon 16 but also exon 11 and is associated with less favorable clinical outcome. 14 refs., 2 figs., 3 tabs.

  16. Selected case from the Arkadi M. Rywlin International Pathology Slide Club: carcinoma of the transverse colon in a young girl.

    Science.gov (United States)

    Galliani, Carlos A; Sanchez, Irene C; D'Errico, Maria M; Bisceglia, Michele

    2015-05-01

    We report a case of a 14-year-old female with primary adenocarcinoma of the transverse colon. She was hospitalized after presenting with abdominal pain and signs of intestinal obstruction. There was no health antecedent or family history of neoplasia. Physical examination revealed a distended abdomen. Tenderness was elicited to palpation of the right lower quadrant. Magnetic resonance imaging of the abdomen revealed obstructive signs, with a constricting lesion in the mid-transverse colon of probable neoplastic nature. Laparoscopic segmental resection of the colon was followed by standard right hemicolectomy. A circumferential mid-transverse tumor was diagnosed as primary colorectal carcinoma (CRC) of signet-ring cell type, AJCC stage IIIC, Dukes' C stage. On the basis of immunohistochemistry and clinical data, hereditary nonpolyposis and hamartomatous colorectal cancer syndromes were excluded. Involvement of either the p53, BRAF, or K-RAS genes was ruled out by immunohistochemistry profiling and genetic testing. The neoplasm was categorized as sporadic. The possibility of activation of the Wnt signaling pathway was suspected, because of a defective turnover of the β-catenin protein. Postoperatively, the patient was treated with both systemic and intra-abdominal adjuvant chemotherapy, including oxaliplatin. Between 18 and 24 months after diagnosis, intra-abdominal tumor recurrences were detected. The patient underwent bilateral oophorectomies for Krukenberg tumors and received salvage chemotherapy. Recently, additional recurrent metastatic retroperitoneal disease caused hydronephrosis. The retroperitoneal mass was debulked and a ureteric stent was placed. At the time of this writing, 43 months after diagnosis, the patient is receiving FOLFOX chemotherapy combined with panitumumab. CRC of childhood is exceedingly rare, generally develops in the setting of unrecognized genetic predisposing factors to cancer, presents with advanced disease, is high grade, and tends

  17. [A case of adenosquamous carcinoma of the sigmoid colon with inferior mesenteric vein thrombosis].

    Science.gov (United States)

    Otsuka, Ryota; Maruyama, Takashi; Tanaka, Hajime; Matsuzaki, Hiroshi; Natsume, Toshiyuki; Miyazaki, Akinari; Sato, Yayoi; Sazuka, Tetsutaro; Yamamoto, Yuji; Yoshioka, Takafumi; Kanada, Yoko; Yanagihara, Akitoshi; Yokoyama, Masaya; Kobayashi, Hiroshi; Shimizu, Shinichiro

    2014-11-01

    A 63-year-old man who had been admitted to another institute with sepsis and renal failure was referred to our hospital after computed tomography (CT) findings showed thickening of the walls in the sigmoid colon and a defect in contrast enhancement in the portal and inferior mesenteric veins. Emergency sigmoid colon resection with D2 lymphadenectomy was performed after detection of perforation due to sigmoid colon cancer. The histopathological diagnosis was adenosquamous carcinoma, pSS, int, INF b, ly1, v0, pN2, pStage IIIband inferior mesenteric vein thrombosis. He was discharged on day 12, and we administered anticoagulant warfarin therapy.

  18. CT evaluation of colon carcinoma: emphasis on distant lymph node invasion and liver metastases

    International Nuclear Information System (INIS)

    Chung, Kyung II; Cho, Kyoung Sik; Lee, Moon Gyu; Baek, Seung Yeon; Auh, Yong Ho; Kim, Jin Cheon

    1993-01-01

    Even though the value of computed tomography (CT) used to detect the colon carcinoma with minimal invasion is limited, its usefulness in the evaluation of the extent of disease such as hepatic metastasis or distant lymph node invasion has been emphasized. Accurate evaluation of colon carcinoma requires both high sensitivity and specificity for the presence of local, regional, and distant tumor spreads. The precise role of these modalities are still being debated. To examine the role of CT in the evaluation of colon carcinoma, CT scans obtained during the past 2 years in 56 patients with surgically proven colon carcinoma were reviewed and the findings correlated with pathologic results. The sensitivity and accuracy of CT for peri colic fat infiltration were 86, 58 and 80% respectively. Those of regional node were 60, 83 and 75% and distant node 67, 100 and 95%. Liver metastases showed sensitivity, specificity and accuracy of 83, 98, 96% and peritoneal metastases 67, 94 and 89% respectively. CT detected local invasion with fair degree of accuracy but the true value of CT lie in the detection of distant invasions such as liver and distant lymph node metastases thereby leading to preclusion of unnecessary procedures and implementation of appropriate procedures

  19. Hypercalcaemia in a patient with fatal adenosquamous carcinoma of the colon

    International Nuclear Information System (INIS)

    Links, M.; Ho, Happy; Clingan, Ph.; Diamond, T.

    1994-01-01

    This article reports a rare manifestation of metastatic adenosquamous carcinoma of the colon in a patient presenting with humoral hypercalcaemia of malignancy mediated by parathyroid hormone related peptide (PTHrP). A 58-year-old man with metastatic adenosquamous carcinoma of the colon presented with hypercalcaemia. A technetium bone scan was performed and excluded osteolytic bone secondaries. A negative parathyroid subtraction scan and a low serum immunoreactive parathyroid hormone level made the diagnosis of primary hyperparathyroidism unlikely. The diagnosis of humoral hypercalcaemia of malignancy was considered on the basis of an elevated serum PTHrP level and positive tumour immunoreactivity to PTHrP antiserum. The hypercalcaemia was effectively treated on two occasions with intravenous administration of aminohydroxy propilidene diphosphonate. Despite interventional chemotherapy, the patient died of progressive carcinomatosis. It is concluded that hypercalcaemia is an extremely rare occurrence in carcinoma of the colon, This being the first documented case of humoral hyper-calcaemia of malignancy associated with adenosquamous carcinoma of the colon mediated by PTHrP. 11 refs., 1 fig

  20. Scintigraphic demonstration of acute gastrointestinal bleeding caused by gallbladder carcinoma eroding the colon

    Energy Technology Data Exchange (ETDEWEB)

    Czerniak, A.; Zwas, S.T.; Rabau, M.Y.; Avigad, I.; Borag, B.; Wolfstein, I.

    1985-08-01

    Massive lower gastrointestinal (GI) bleeding caused by gallbladder carcinoma eroding into the colonic wall was demonstrated accurately by Tc-99m RBCs. In addition, retrograde bleeding into the gallbladder was also identified while arteriography did not show contrast extravasation. This case supports the use of Tc-99m RBCs over Tc-99m sulfur colloid for more accurate localization of lower GI bleeding.

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

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    Musharraf Husain

    2015-01-01

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

  2. Expression profiles of proliferative and antiapoptotic genes in sporadic and colitis-related mouse colon cancer models

    Czech Academy of Sciences Publication Activity Database

    Švec, J.; Ergang, Peter; Mandys, V.; Kment, M.; Pácha, Jiří

    2010-01-01

    Roč. 91, č. 1 (2010), s. 44-53 ISSN 0959-9673 R&D Projects: GA MZd(CZ) NS9982; GA MZd(CZ) 1A8651 Institutional research plan: CEZ:AV0Z50110509 Keywords : colorectal carcinoma * mouse Subject RIV: FP - Other Medical Disciplines Impact factor: 2.127, year: 2010

  3. Differential expression of colon cancer associated transcript1 (CCAT1) along the colonic adenoma-carcinoma sequence

    International Nuclear Information System (INIS)

    Alaiyan, Bilal; Trink, Barry; Gure, Ali O; Nissan, Aviram; Ilyayev, Nadia; Stojadinovic, Alexander; Izadjoo, Mina; Roistacher, Marina; Pavlov, Vera; Tzivin, Victoria; Halle, David; Pan, Honguang

    2013-01-01

    The transition from normal epithelium to adenoma and, to invasive carcinoma in the human colon is associated with acquired molecular events taking 5-10 years for malignant transformation. We discovered CCAT1, a non-coding RNA over-expressed in colon cancer (CC), but not in normal tissues, thereby making it a potential disease-specific biomarker. We aimed to define and validate CCAT1 as a CC-specific biomarker, and to study CCAT1 expression across the adenoma-carcinoma sequence of CC tumorigenesis. Tissue samples were obtained from patients undergoing resection for colonic adenoma(s) or carcinoma. Normal colonic tissue (n = 10), adenomatous polyps (n = 18), primary tumor tissue (n = 22), normal mucosa adjacent to primary tumor (n = 16), and lymph node(s) (n = 20), liver (n = 8), and peritoneal metastases (n = 19) were studied. RNA was extracted from all tissue samples, and CCAT1 expression was analyzed using quantitative real time-PCR (qRT-PCR) with confirmatory in-situ hybridization (ISH). Borderline expression of CCAT1 was identified in normal tissue obtained from patients with benign conditions [mean Relative Quantity (RQ) = 5.9]. Significant relative CCAT1 up-regulation was observed in adenomatous polyps (RQ = 178.6 ± 157.0; p = 0.0012); primary tumor tissue (RQ = 64.9 ± 56.9; p = 0.0048); normal mucosa adjacent to primary tumor (RQ = 17.7 ± 21.5; p = 0.09); lymph node, liver and peritoneal metastases (RQ = 11,414.5 ± 12,672.9; 119.2 ± 138.9; 816.3 ± 2,736.1; p = 0.0001, respectively). qRT-PCR results were confirmed by ISH, demonstrating significant correlation between CCAT1 up-regulation measured using these two methods. CCAT1 is up-regulated across the colon adenoma-carcinoma sequence. This up-regulation is evident in pre-malignant conditions and through all disease stages, including advanced metastatic disease suggesting a role in both tumorigenesis and the metastatic process

  4. Meat consumption and K-ras mutations in sporadic colon and rectal cancer in The Netherlands Cohort Study

    NARCIS (Netherlands)

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

    2005-01-01

    Case-cohort analyses were performed on meat and fish consumption in relation to K-ras mutations in 448 colon and 160 rectal cancers that occurred during 7.3 years of follow-up, excluding the first 2.3 years, and 2948 subcohort members of The Netherlands Cohort Study on diet and cancer. Adjusted

  5. Medullary colonic carcinoma with microsatellite instability has lower survival compared with conventional colonic adenocarcinoma with microsatellite instability

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    Miguel A. Gómez-Álvarez

    2016-12-01

    Full Text Available Introduction: Colorectal medullary carcinoma (MC is a rare subtype of poorly differentiated adenocarcinoma (PDA with unclear prognostic significance. Microsatellite instable (MSI colorectal carcinomas have demonstrated better prognosis in clinical stage II. Aim: To analyze the survival and clinicopathological characteristics of MCs versus PDAs with MSI in clinical stage III. Material and methods: We studied 22 cases of PDAs with MSI versus 10 MCs. Results : Of the 10 MCs, 7 patients were men; the mean age was 57.8 ±5.6 years. The mean tumor size was 9.6 ±4.1 cm, and the primary site was the right colon in 9; 7 patients showed lymph node metastases (LNM and lymphovascular invasion (LVI. Of the 22 PDA cases, 12 (54.5% were women with a mean age of 75 ±16.1 years. The mean tumor size was 6.4 ±3.2 cm. Twelve (54.5% presented in the right colon, 21 (95.5% showed LNM and 7 (31.8% LVI. Follow-up was 32 ±8 months, with a 5-year overall survival of 42.9% for MCs and 76.6% for PDAs (p = 0.048. Univariate analysis found local recurrence (p = 0.001 and medullary subtype (p = 0.043 associated with lower survival. Conclusions : Medullary carcinomas were of greater tumor size and associated with more LVI and worse survival versus PDAs with MSI in stage III.

  6. TP53 mutations in ovarian carcinomas from sporadic cases and carriers of two distinct BRCA1 founder mutations; relation to age at diagnosis and survival

    International Nuclear Information System (INIS)

    Kringen, Pedro; Wang, Yun; Dumeaux, Vanessa; Kristensen, Gunnar; Borresen-Dale, Anne-Lise; Dorum, Anne

    2005-01-01

    Ovarian carcinomas from 30 BRCA1 germ-line carriers of two distinct high penetrant founder mutations, 20 carrying the 1675delA and 10 the 1135insA, and 100 sporadic cases were characterized for somatic mutations in the TP53 gene. We analyzed differences in relation to BRCA1 germline status, TP53 status, survival and age at diagnosis, as previous studies have not been conclusive. DNA was extracted from paraffin embedded formalin fixed tissues for the familial cases, and from fresh frozen specimen from the sporadic cases. All cases were treated at our hospital according to protocol. Mutation analyses of exon 2 – 11 were performed using TTGE, followed by sequencing. Survival rates for BRCA1-familial cases with TP53 mutations were not significantly lower than for familial cases without TP53 mutations (p = 0.25, RR = 1.64, 95% CI [0.71–3.78]). Median age at diagnosis for sporadic (59 years) and familial (49 years) cases differed significantly (p < 0.001) with or without TP53 mutations. Age at diagnosis between the two types of familial carriers were not significantly different, with median age of 47 for 1675delA and 52.5 for 1135insA carriers (p = 0.245). For cases ≥50 years at diagnosis, a trend toward longer survival for sporadic over familial cases was observed (p = 0.08). The opposite trend was observed for cases <50 years at diagnosis. There do not seem to be a protective advantage for familial BRCA1 carriers without TP53 mutations over familial cases with TP53 mutations. However, there seem to be a trend towards initial advantage in survival for familial cases compared to sporadic cases diagnosed before the age of 50 both with and without TP53 mutations. However, this trend diminishes over time and for cases diagnosed ≥50 years the sporadic cases show a trend towards an advantage in survival over familial cases. Although this data set is small, if confirmed, this may be a link in the evidence that the differences in ovarian cancer survival reported, are

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

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    Raquel Albero-González

    2017-03-01

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

  8. Preliminary clinical application of radioimmunoimaging with 111In labelled anti-colon carcinoma monoclonal antibody

    International Nuclear Information System (INIS)

    Han Bing

    1992-01-01

    2C 10 is an anti-colorectal carcinoma monoclonal antibody which cross reacts with gastric and ovarian carcinomas. The antibody has shown good tumor location in nude mice after labelling with 111 In. 15 patients have been clinically tested with 111 In-2C 10 , in whom 11 were colorectal carcinomas,2 gastric and 2 ovarian carcinomas. Most of the cases were adenocarcinoma. 10 cases were confirmed surgically and pathologically. The largest tumor was 10 x 8 x 7 cm 3 (ovarian carcinoma) and the smallest ones were 3 x 3 x 2 cm 3 (gastric carcinoma)and 3 x 3 x 5 cm 3 (rectal carcinoma). The other 5 cases were proven by fibre endoscopy, B-ultrasonography and X-ray. Routine blood and urine test and examinations on liver and renal functions as well as measurement of serum CEA level were also performed. The antibody, which had been proven bacteria and pyrogen free, was labelled with 111 In under sterile conditions. 2-3 mCi 111 In -2C 10 (1 mg) diluted in 100 ml normal saline was administered by intravenous drip. Most of the patients were gamma scanned 72 hours after injection. Tumor specimens were also imaged. The radioactivities in tumors and tissues on cutting edges were measured. Positive results were obtained in 10/11 of the colorectal cancer patients. Two ovarian cancers were positive while the two gastric carcinomas showed negative images. One ovarian cancer metastasis to colon and one recurrent colon cancer were detected only by RII. The results have confirmed the advantages of RII over CT and ultrasonography. The high radioactivity in liver, however, is a conspicuous problem to be resolved

  9. Spatial and temporal heparanase expression in colon mucosa throughout the adenoma-carcinoma sequence.

    Science.gov (United States)

    Doviner, Victoria; Maly, Bella; Kaplan, Victoria; Gingis-Velitski, Svetlana; Ilan, Neta; Vlodavsky, Israel; Sherman, Yoav

    2006-06-01

    Heparanase is a mammalian endo-beta-D-glucuronidase that cleaves heparan sulfate side chains at a limited number of sites. Such enzymatic activity is thought to participate in degradation and remodeling of the extracellular matrix and to facilitate cell invasion associated with tumor metastasis, angiogenesis and inflammation. Traditionally, heparanase activity was well correlated with the metastatic potential of a large number of tumor-derived cell types. More recently, heparanase upregulation has been documented in an increasing number of primary human tumors, correlating with poor postoperative survival and increased tumor vascularity. Here, we employed anti-heparanase 733 polyclonal antibody that preferentially recognizes the 50 kDa active heparanase subunit over the 65 kDa proenzyme, as well as anti-heparanase 92.4 monoclonal antibody that recognizes both the latent and the active enzyme, to follow heparanase expression, processing and localization throughout the adenoma-carcinoma transition of the colon epithelium. Normal (nondysplastic) mucosa of the large bowel near epithelial neoplasms, as well as areas of mild dysplasia in adenomas, exhibited a strong reactivity with antibody 733 that became even stronger in foci of moderate dysplasia. Interestingly, although reactivity with antibody 733 was markedly reduced in severe dysplasia and in colorectal carcinoma, response to antibody 92.4 exhibited the opposite trend and staining intensities increased in parallel with tumor stage, the highest being in carcinoma cells. Involvement of latent heparanase (detected by 92.4, but not by 733 antibody) in tumor progression was suggested by activation of the Akt/PKB signal transduction pathway upon heparanase overexpression or exogenous addition to HT29 human colon carcinoma cells. These results suggest that heparanase expression is induced during colon carcinogenesis, and that its processing, conformation and localization are tightly regulated during the course of colon

  10. Delayed colon perforation after palliative treatment for rectal carcinoma with bare rectal stent: a case report

    International Nuclear Information System (INIS)

    Han, Young Min; Lee, Jeong Min; Lee, Tae Hoon

    2000-01-01

    In order to relieve mechanical obstruction caused by rectal carcinoma, a bare rectal stent was inserted in the sigmoid colon of a 70-year-old female. The procedure was successful, and for one month the patient made good progress. She then complained of abdominal pain, however, and plain radiographs of the chest and abdomen revealed the presence of free gas in the subdiaphragmatic area. Surgical findings showed that a spur at the proximal end of the bare rectal stent had penetrated the rectal mucosal wall. After placing a bare rectal stent for the palliative treatment of colorectal carcinoma, close follow-up to detect possible perforation of the bowel wall is necessary

  11. Two case reports of metastases from colon carcinoma to the thyroid.

    Science.gov (United States)

    Poon, D; Toh, H C; Sim, C S

    2004-01-01

    Secondary malignancy of the thyroid gland is uncommon, but it is a problem requiring ongoing recognition. As it is more common than primary thyroid malignancy, metastatic disease involving the thyroid gland should be actively excluded in a patient with enlarging or abnormal thyroid gland and a previously known primary tumour. We report 2 cases of primary colon carcinoma with metastasis to the thyroid gland that mimicked thyroid anaplastic carcinoma. In both cases, airway compromise was evident. Emergency tracheostomy was necessary in the first case with subsequent oxaliplatin-based chemotherapy providing palliation of symptom of breathlessness, with significant reduction in size of thyroidal metastasis. Palliative thyroidectomy relieved airway compromise in the second case. Our case report highlights the importance of early recognition of thyroidal metastases from a colonic primary as life-threatening airway compromise may otherwise rapidly ensue.

  12. Preoperative CT staging of colon carcinoma (excluding the recto-sigmoid region)

    International Nuclear Information System (INIS)

    Acunas, B.; Rozanes, I.; Acunas, G.; Sayi, I.; Gokmen, E.; Celik, L.

    1990-01-01

    28 Patients with colon carcinoma (excluding the recto-sigmoid region) underwent preoperative staging with computed tomography (CT). The CT had a sensitivity of 60 and 67 per cent for detection of extramural invasion, 75 per cent sensitivity and specificity for lymph node metastases and a sensitivity of 87 per cent and specificity of 95 per cent for liver metastases. Compared with the modified Dukes classification, CT correctly staged 50 per cent of the patients with Dukes A lesions; 40 per cent with Dukes B, 75 per cent with Dukes C and 85 per cent with Dukes D lesions. The data presented in this study showed that CT has limitations in the sensitivity and accuracy of staging local colonic carcinoma. However, the authors recommend its use for patients who are clinically suspected of having extensive disease. (author). 10 refs.; 4 figs.; 2 tabs

  13. Secretory cell outgrowths, p53 signatures, and serous tubal intraepithelial carcinoma in the fallopian tubes of patients with sporadic pelvic serous carcinoma

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    Neha Mittal

    2016-01-01

    Full Text Available Context: High-grade serous carcinomas of ovarian, tubal, and peritoneal origin are together referred as pelvic serous carcinoma. The fallopian tubes, ovarian surface epithelium, and the tuboperitoneal junctional epithelium are all implicated in pelvic serous carcinogenesis. Aims: The aim of this study is to identify putative precursor lesions of serous carcinoma including secretory cell outgrowths (SCOUTs, serous tubal intraepithelial carcinoma (STIC, and p53 signatures and assign its probable site of origin. Settings and Design: Prospective case-control study of consecutive specimen comprising 32 serous carcinomas and 31 controls (10 normal adnexa, 10 benign and 6 atypically proliferative surface epithelial tumors, and 5 other carcinomas. Subjects and Methods: Sectioning and extensive examination of the fimbrial end (SEE-FIM protocol along with immunohistochemistry for Bcl-2, p53, and Ki-67 was employed for evaluating invasive carcinoma and precursor lesions in cases versus controls. Results: SCOUT, p53 signatures, and STIC were most frequent in the serous carcinomas. p53 signatures and STIC were always seen in the fimbrial end. STICs were exclusively present in serous carcinomas, more common in ipsilateral tubes of cases with dominant ovarian mass. Multifocal p53 signatures with STIC were seen in 7 (21.9% cases. STIC was present with or without an invasive carcinoma in 25% and in 6.25% of cases of pelvic serous carcinomas, respectively. The junctional epithelia did not show any lesion in any group. Conclusions: SEE-FIM protocol is recommended for evaluation of sporadicpelvic (ovarian/tubal/peritoneal serous carcinoma. Based on the presence of STIC or invasive carcinoma, nearly 60% of all pelvic serous carcinomas are of fallopian tubal origin.

  14. Secretory cell outgrowths, p53 signatures, and serous tubal intraepithelial carcinoma in the fallopian tubes of patients with sporadic pelvic serous carcinoma.

    Science.gov (United States)

    Mittal, Neha; Srinivasan, Radhika; Gupta, Nalini; Rajwanshi, Arvind; Nijhawan, Raje; Gautam, Upasana; Sood, Swati; Dhaliwal, Lakhbir

    2016-01-01

    High-grade serous carcinomas of ovarian, tubal, and peritoneal origin are together referred as pelvic serous carcinoma. The fallopian tubes, ovarian surface epithelium, and the tuboperitoneal junctional epithelium are all implicated in pelvic serous carcinogenesis. The aim of this study is to identify putative precursor lesions of serous carcinoma including secretory cell outgrowths (SCOUTs), serous tubal intraepithelial carcinoma (STIC), and p53 signatures and assign its probable site of origin. Prospective case-control study of consecutive specimen comprising 32 serous carcinomas and 31 controls (10 normal adnexa, 10 benign and 6 atypically proliferative surface epithelial tumors, and 5 other carcinomas). Sectioning and extensive examination of the fimbrial end (SEE-FIM) protocol along with immunohistochemistry for Bcl-2, p53, and Ki-67 was employed for evaluating invasive carcinoma and precursor lesions in cases versus controls. SCOUT, p53 signatures, and STIC were most frequent in the serous carcinomas. p53 signatures and STIC were always seen in the fimbrial end. STICs were exclusively present in serous carcinomas, more common in ipsilateral tubes of cases with dominant ovarian mass. Multifocal p53 signatures with STIC were seen in 7 (21.9%) cases. STIC was present with or without an invasive carcinoma in 25% and in 6.25% of cases of pelvic serous carcinomas, respectively. The junctional epithelia did not show any lesion in any group. SEE-FIM protocol is recommended for evaluation of sporadicpelvic (ovarian/tubal/peritoneal) serous carcinoma. Based on the presence of STIC or invasive carcinoma, nearly 60% of all pelvic serous carcinomas are of fallopian tubal origin.

  15. Increased expression of interleukin-21 along colorectal adenoma-carcinoma sequence and its predicating significance in patients with sporadic colorectal cancer.

    Science.gov (United States)

    Cui, Guanglin; Yuan, Aping; Zhu, Li; Florholmen, Jon; Goll, Rasmus

    2017-10-01

    The role and significance of interleukin (IL)-21 in the development of sporadic CRC have not been well defined. The aim of this study is therefore to investigate the dynamics of the IL-21 along colorectal adenoma-carcinoma sequence and to evaluate the impact of IL-21 on clinicopathological parameters and CRC prognosis. The real-time PCR results showed that the level of IL-21 in adenomas (n=50) and sporadic CRC (n=50) were significantly higher than that in normal controls (n=18), which were predominately observed in the adenoma/CRC stroma. Analysis revealed that IL-21 level was correlated with the overall survival time in CRC patients. Double immunofluorescence observations confirmed that IL-21 positive cells were mostly natural killer cells and T lymphocytes in the tumor stroma. These results indicate that significant increased IL-21 expression present within the adenoma/CRC microenvironment might have a potential predicating significance for survival time in patients with CRC. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Oncocytic Variant of Medullary Thyroid Carcinoma: A Rare Case of Sporadic Multifocal and Bilateral RET Wild-Type Neoplasm with Revision of the Literature.

    Science.gov (United States)

    Vinciguerra, Gian Luca Rampioni; Noccioli, Niccolò; Cippitelli, Claudia; Minucci, Angelo; Capoluongo, Ettore; Bartolazzi, Armando

    2016-11-17

    Oncocytic variant of medullary thyroid carcinoma (OV-MTC) is a very unusual entity, up to date only 17 cases have been reported in the literature. MTC is a neuro-endocrine malignancy arising from the para-follicular C cells of the thyroid gland. It generally has a slight female predominance and appears as a single lesion. However in the Multiple Endocrine Neoplasia Syndrome 2, linked to the point mutation of RET oncogene, multifocal MTCs may also occur. Herein, we report the case of a 75 years old man with a rare form of sporadic multifocal and bilateral OV-MTC expressing wild-type RET gene. The histological and molecular features of this rare entity are presented and discussed with revision of the pertinent literature.

  17. Oncocytic variant of medullary thyroid carcinoma: a rare case of sporadic multifocal and bilateral RET wild-type neoplasm with revision of the literature

    Directory of Open Access Journals (Sweden)

    Gian Luca Rampioni Vinciguerra

    2016-12-01

    Full Text Available Oncocytic variant of medullary thyroid carcinoma (OV-MTC is a very unusual entity, up to date only 17 cases have been reported in the literature. MTC is a neuro-endocrine malignancy arising from the para-follicular C cells of the thyroid gland. It generally has a slight female predominance and appears as a single lesion. However in the Multiple Endocrine Neoplasia Syndrome 2, linked to the point mutation of RET oncogene, multifocal MTCs may also occur. Herein, we report the case of a 75 years old man with a rare form of sporadic multifocal and bilateral OV-MTC expressing wild-type RET gene. The histological and molecular features of this rare entity are presented and discussed with revision of the pertinent literature.

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

    Directory of Open Access Journals (Sweden)

    María Isabel Villegas

    1989-02-01

    Full Text Available

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

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

  19. The value of MR imaging in the diagnosis of colonic carcinoma

    International Nuclear Information System (INIS)

    Qian Nong; Pan Changjie; Xiang Jianbo; Zhang Shixian

    2003-01-01

    Objective: To investigate the MR imaging findings of colonic carcinoma and the diagnostic value of MRI. Methods: Multi-planar and multi-sequence MRI scanning, before and after contrast enhancement, were performed in 40 patients with colonic cancer. The patients were fasted for 12 hours, prepared with clean clysis or senna at night before study, given 10 mg of anisodamine 10 minutes before study, and then infused with 800-1000 ml physiological saline immediately before study by anus. Dukes staging and resectability evaluation were made in 32 patients before surgery and meanwhile the results were compared with pathology. Results: Colonic anatomy and surrounding organs were clearly demonstrated on MRI in 40 patients with colonic cancer, particularly in recta and sigmoid flexure. The tumours showed iso-intensity on T 1 WI, iso-intensity or slight high-intensity signal on T 2 WI, and high-intensity signal on SPIR. Remarkable enhancement was seen in 35/40 (87.5%). Invasion of surrounding organs occurred in 8/40(20.0%) and MRI revealed 6; Meanwhile, MRI revealed lymph node metastasis in 8 out of 12 cases. 32 patients were regarded as resectable before surgery, and 8 patients as unresectable. Four patients were overestimated, the accuracy of preoperative evaluation for the resectability was 87.5%, and the detecting rate of colonic cancer was 100.0%. Conclusion: MRI can clearly show the colonic wall thickness, anatomic structure and surrounding anatomy. For the diagnosis of colonic cancer, MRI can not only demonstrate all its morphologic features, such as mass, thickened wall, and invasion of adjacent organs, but also swollen lymph node and metastasis in abdominal cavity. MRI is very helpful in the diagnosis, staging , and resectability evaluation of colonic cancer

  20. Relationship of mismatch repair proteins and survivin in colon polyps and carcinomas.

    Science.gov (United States)

    Adamkov, Marian; Furjelová, Martina; Horáček, Jaroslav; Benčat, Marián; Kružliak, Peter

    2014-07-01

    Mismatch repair genes (MMR) play an essential role in DNA repair. MMR mutations predominantly in MLH1, MSH2, MSH6, PMS2, and rarely in PMS1, may cause the production of abnormally short or inactivated proteins. The antiapoptotic protein survivin functions in the inhibition of apoptosis, regulation of cell division and also enhances angiogenesis. Both MMRP and survivin are considered to be powerful prognostic parameters. This study was designed to determine the relationship between MMRP and survivin in colon lesions. The study included 113 cases of colon carcinoma and 51 cases of colon polyps. Survivin expression and MMRP status were assessed by immunohistochemistry. In each section, expression, intensity of immunostaining and percentage of labeled cells were analyzed. In carcinomas, immunoreaction was detected in 100/113 cases for MLH1 (88.5%), 112/113 cases for MSH2 (99.1%), 110/113 cases for MSH6 (97.3%), and 103/113 cases for PMS2 (91.2%). Survivin was shown in 47/113 cases (41.6%). The statistical analysis confirmed a significant correlation between the expression of MMRP and survivin in the assessed parameters. All 51 polyp samples were positive for MLH1, MSH2, MSH6 and PMS2. Only 8 of those (15.7%) were positive for survivin. Statistically significant differences were observed between the expression of MMRP and survivin. In conclusion, this study revealed that MMRP may suppress the antiapoptotic function of survivin through p53 inactivation of its promoter in grade 1 and grade 2 colon carcinomas. Copyright © 2014 Elsevier GmbH. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-07-01

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

  2. Mutations in APC, CTNNB1 and K-ras genes and expression of hMLH1 in sporadic colorectal carcinomas from the Netherlands Cohort Study

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    de Bruïne Adriaan P

    2005-12-01

    Full Text Available Abstract Background The early to intermediate stages of the majority of colorectal tumours are thought to be driven by aberrations in the Wnt (APC, CTNNB1 and Ras (K-ras pathways. A smaller proportion of cancers shows mismatch repair deficiency. The aim of this study was to analyse the co-occurrence of these genetic alterations in relation to tumour and patient characteristics. Methods In a group of 656 unselected sporadic colorectal cancer patients, aberrations in the APC, K-ras, CTNNB1 genes, and expression of hMLH1 were investigated. Additionally, tumours were divided in groups based on molecular features and compared with respect to patient's age at diagnosis, sex, family history of colorectal cancer, tumour sub-localisation, Dukes' stage and differentiation. Results Mutations at the phosphorylation sites (codons 31, 33, 37, and 45 in the CTNNB1 gene were observed in tumours from only 5/464 patients. Tumours with truncating APC mutations and activating K-ras mutations in codons 12 and 13 occurred at similar frequencies (37% (245/656 and 36% (235/656, respectively. Seventeen percent of tumours harboured both an APC and a K-ras mutation (109/656. Nine percent of all tumours (58/656 lacked hMLH1 expression. Patients harbouring a tumour with absent hMLH1 expression were older, more often women, more often had proximal colon tumours that showed poorer differentiation when compared to patients harbouring tumours with an APC and/or K-ras mutation. Conclusion CTNNB1 mutations seem to be of minor importance in sporadic colorectal cancer. The main differences in tumour and patient characteristics are found between groups of patients based on mismatch repair deficiency.

  3. Mutations in APC, CTNNB1 and K-ras genes and expression of hMLH1 in sporadic colorectal carcinomas from the Netherlands Cohort Study

    International Nuclear Information System (INIS)

    Lüchtenborg, Margreet; Weijenberg, Matty P; Wark, Petra A; Saritas, A Merdan; Roemen, Guido MJM; Muijen, Goos NP van; Bruïne, Adriaan P de; Brandt, Piet A van den; Goeij, Anton FPM de

    2005-01-01

    The early to intermediate stages of the majority of colorectal tumours are thought to be driven by aberrations in the Wnt (APC, CTNNB1) and Ras (K-ras) pathways. A smaller proportion of cancers shows mismatch repair deficiency. The aim of this study was to analyse the co-occurrence of these genetic alterations in relation to tumour and patient characteristics. In a group of 656 unselected sporadic colorectal cancer patients, aberrations in the APC, K-ras, CTNNB1 genes, and expression of hMLH1 were investigated. Additionally, tumours were divided in groups based on molecular features and compared with respect to patient's age at diagnosis, sex, family history of colorectal cancer, tumour sub-localisation, Dukes' stage and differentiation. Mutations at the phosphorylation sites (codons 31, 33, 37, and 45) in the CTNNB1 gene were observed in tumours from only 5/464 patients. Tumours with truncating APC mutations and activating K-ras mutations in codons 12 and 13 occurred at similar frequencies (37% (245/656) and 36% (235/656), respectively). Seventeen percent of tumours harboured both an APC and a K-ras mutation (109/656). Nine percent of all tumours (58/656) lacked hMLH1 expression. Patients harbouring a tumour with absent hMLH1 expression were older, more often women, more often had proximal colon tumours that showed poorer differentiation when compared to patients harbouring tumours with an APC and/or K-ras mutation. CTNNB1 mutations seem to be of minor importance in sporadic colorectal cancer. The main differences in tumour and patient characteristics are found between groups of patients based on mismatch repair deficiency

  4. Increased mRNA expression of a laminin-binding protein in human colon carcinoma: Complete sequence of a full-length cDNA encoding the protein

    International Nuclear Information System (INIS)

    Yow, Hsiukang; Wong, Jau Min; Chen, Hai Shiene; Lee, C.; Steele, G.D. Jr.; Chen, Lanbo

    1988-01-01

    Reliable markers to distinguish human colon carcinoma from normal colonic epithelium are needed particularly for poorly differentiated tumors where no useful marker is currently available. To search for markers the authors constructed cDNA libraries from human colon carcinoma cell lines and screened for clones that hybridize to a greater degree with mRNAs of colon carcinomas than with their normal counterparts. Here they report one such cDNA clone that hybridizes with a 1.2-kilobase (kb) mRNA, the level of which is ∼9-fold greater in colon carcinoma than in adjacent normal colonic epithelium. Blot hybridization of total RNA from a variety of human colon carcinoma cell lines shows that the level of this 1.2-kb mRNA in poorly differentiated colon carcinomas is as high as or higher than that in well-differentiated carcinomas. Molecular cloning and complete sequencing of cDNA corresponding to the full-length open reading frame of this 1.2-kb mRNA unexpectedly show it to contain all the partial cDNA sequence encoding 135 amino acid residues previously reported for a human laminin receptor. The deduced amino acid sequence suggests that this putative laminin-binding protein from human colon carcinomas consists of 295 amino acid residues with interesting features. There is an unusual C-terminal 70-amino acid segment, which is trypsin-resistant and highly negatively charged

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

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    Ulrike Weirauch

    2013-07-01

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

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

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    Iannace Alessandro

    2011-05-01

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

  7. Establishment, characterization and chemosensitivity of three mismatch repair deficient cell lines from sporadic and inherited colorectal carcinomas.

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    Claudia Maletzki

    Full Text Available BACKGROUND: Colorectal cancer (CRC represents a morphologic and molecular heterogenic disease. This heterogeneity substantially impairs drug effectiveness and prognosis. The subtype of mismatch repair deficient (MMR-D CRCs, accounting for about 15% of all cases, shows particular differential responses up to resistance towards currently approved cytostatic drugs. Pre-clinical in vitro models representing molecular features of MMR-D tumors are thus mandatory for identifying biomarkers that finally help to predict responses towards new cytostatic drugs. Here, we describe the successful establishment and characterization of three patient-derived MMR-D cell lines (HROC24, HROC87, and HROC113 along with their corresponding xenografts. METHODOLOGY: MMR-D cell lines (HROC24, HROC87, and HROC113 were established from a total of ten clinicopathological well-defined MMR-D cases (120 CRC cases in total. Cells were comprehensively characterized by phenotype, morphology, growth kinetics, invasiveness, and molecular profile. Additionally, response to clinically relevant chemotherapeutics was examined in vitro and in vivo. PRINCIPAL FINDINGS: Two MMR-D lines showing CIMP-H derived from sporadic CRC (HROC24: K-ras(wt, B-raf(mut, HROC87: K-ras(wt, B-raf(mut, whereas the HROC113 cell line (K-ras(mut, B-raf(wt was HNPCC-associated. A diploid DNA-status could be verified by flow cytometry and SNP Array analysis. All cell lines were characterized as epithelial (EpCAM(+ tumor cells, showing surface tumor marker expression (CEACAM(+. MHC-class II was inducible by Interferon-γ stimulation. Growth kinetics as well as invasive potential was quite heterogeneous between individual lines. Besides, MMR-D cell lines exhibited distinct responsiveness towards chemotherapeutics, even when comparing in vitro and in vivo sensitivity. CONCLUSIONS: These newly established and well-characterized, low-passage MMR-D cell lines provide a useful tool for future investigations on the

  8. Prospective comparison of open vs. laparoscopic colon surgery for carcinoma. Five-year results.

    Science.gov (United States)

    Franklin, M E; Rosenthal, D; Abrego-Medina, D; Dorman, J P; Glass, J L; Norem, R; Diaz, A

    1996-10-01

    Laparoscopy for colonic diseases began in 1990 and has established a role in benign disease. Early observations and experiences demonstrated feasibility of laparoscopic surgery for a variety of colonic disease processes, but the applicability to colonic carcinoma was unclear. In 1990, we began a comparative study of open (OCR) vs. laparoscopic (LCR) approach to colon cancer. The study progressed 65 months, with 224 patients in OCR group and 191 patients in LCR group. Parameters studied are stage, location, length of specimen, number of lymph nodes resected, margins, postoperative course, wound complications, recurrence rates, and immediate and long-term survival. OCR were standardized by one group, and LCR were standardized by a second group. All patients undergoing LCR were given freedom to choose either OCR or LCR, and informed consent was obtained. Equal or greater lymph node retrieval, resections, and distal margins were evident with LCR. Benefits with LCR were shown with shorter hospitalization (5.7 vs. 9.7 days), less blood loss, less wound problems (1 vs. 14), and quicker return of bowel function. Survival, recurrence, and death rates were essentially the same. There were no trocar implants in the LCR group. After five years, this study shows that laparoscopy does no harm to the patient, offers comparable oncologic resections, and seems to be patient-friendly, with less pain, quicker return of bowel functions, shortened hospitalization, and quicker return to full activity.

  9. Pigmentation, Melanocyte Colonization, and p53 Status in Basal Cell Carcinoma

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    Lídia M. Frey

    2011-01-01

    Full Text Available Basal cell carcinoma (BCC is the most common neoplasm in the Caucasian population. Only a fraction of BCC exhibits pigmentation. Lack of melanocyte colonization has been suggested to be due to p53-inactivating mutations in the BCC cells interfering with the p53-proopiomelanocortin pathway and the production of alpha melanocyte-stimulating hormone in the tumor. To evaluate this, we determined tumor pigmentation as well as expression of melan-A and of p53 in 49 BCC tissues by means of immunohistochemistry. As expected, we observed a positive relation between tumor pigmentation and melan-A positive intra-tumoral melanocytes. Melanocyte colonization and, to a lesser extent, p53 overexpression showed intraindividual heterogeneity in larger tumors. p53 overexpression, which is indicative of p53 mutations, was not correlated to melanocyte colonization of BCC. Sequencing of exon 5–8 of the p53 gene in selected BCC cases revealed that colonization by melanocytes and BCC pigmentation is neither ablated by p53 mutations nor generally present in BCCs with wild-type p53.

  10. Pigmentation, Melanocyte Colonization, and p53 Status in Basal Cell Carcinoma

    International Nuclear Information System (INIS)

    Frey, L. M.; Houben, R.; Brocker, E. B.

    2011-01-01

    Basal cell carcinoma (BCC) is the most common neoplasm in the Caucasian population. Only a fraction of BCC exhibits pigmentation. Lack of melanocyte colonization has been suggested to be due to p53-inactivating mutations in the BCC cells interfering with the p53-proopiomelanocortin pathway and the production of alpha melanocyte-stimulating hormone in the tumor. To evaluate this, we determined tumor pigmentation as well as expression of melan-A and of p53 in 49 BCC tissues by means of immunohistochemistry. As expected, we observed a positive relation between tumor pigmentation and melan-A positive intra-tumoral melanocytes. Melanocyte colonization and, to a lesser extent, p53 overexpression showed intraindividual heterogeneity in larger tumors. p53 overexpression, which is indicative of p53 mutations, was not correlated to melanocyte colonization of BCC. Sequencing of exon 5-8 of the p53 gene in selected BCC cases revealed that colonization by melanocytes and BCC pigmentation is neither ablated by p53 mutations nor generally present in BCCs with wild-type p53.

  11. Transforming growth factor-β suppresses metastasis in a subset of human colon carcinoma cells

    International Nuclear Information System (INIS)

    Simms, Neka A K; Rajput, Ashwani; Sharratt, Elizabeth A; Ongchin, Melanie; Teggart, Carol A; Wang, Jing; Brattain, Michael G

    2012-01-01

    TGFβ signaling has typically been associated with suppression of tumor initiation while the role it plays in metastasis is generally associated with progression of malignancy. However, we present evidence here for an anti-metastatic role of TGFβ signaling. To test the importance of TGFβ signaling to cell survival and metastasis we compared human colon carcinoma cell lines that are either non-tumorigenic with TGFβ response (FET), or tumorigenic with TGFβ response (FETα) or tumorigenic with abrogated TGFβ response via introduction of dominant negative TGFβRII (FETα/DN) and their ability to metastasize. Metastatic competency was assessed by orthotopic transplantation. Metastatic colony formation was assessed histologically and by imaging. Abrogation of TGFβ signaling through introduction of a dominant negative TGFβ receptor II (TGFβRII) in non-metastatic FETα human colon cancer cells permits metastasis to distal organs, but importantly does not reduce invasive behavior at the primary site. Loss of TGFβ signaling in FETα-DN cells generated enhanced cell survival capabilities in response to cellular stress in vitro. We show that enhanced cellular survival is associated with increased AKT phosphorylation and cytoplasmic expression of inhibitor of apoptosis (IAP) family members (survivin and XIAP) that elicit a cytoprotective effect through inhibition of caspases in response to stress. To confirm that TGFβ signaling is a metastasis suppressor, we rescued TGFβ signaling in CBS metastatic colon cancer cells that had lost TGFβ receptor expression due to epigenetic repression. Restoration of TGFβ signaling resulted in the inhibition of metastatic colony formation in distal organs by these cells. These results indicate that TGFβ signaling has an important role in the suppression of metastatic potential in tumors that have already progressed to the stage of an invasive carcinoma. The observations presented here indicate a metastasis suppressor role for TGF

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

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    Ihab Shafek Atta

    2016-01-01

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

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

    Science.gov (United States)

    Atta, Ihab Shafek; AlQahtani, Fahd Nasser

    2016-01-01

    We are presenting a case associated with papillary thyroid carcinoma, renal cell carcinoma, invasive mammary carcinoma, chondrosarcoma, benign ganglioneuroma, and numerous colon adenomas. The patient had a family history of colon cancer, kidney and bladder cancers, lung cancer, thyroid cancer, leukemia, and throat and mouth cancers. She was diagnosed with colonic villous adenoma at the age of 41 followed by thyroid, renal, and breast cancers and chondrosarcoma at the ages of 48, 64, 71, and 74, respectively. Additionally, we included a table with the most common familial cancer syndromes with one or more benign or malignant tumors diagnosed in our case, namely, FAP, HNPCC, Cowden, Peutz-Jeghers, renal cancer, tuberous sclerosis, VHL, breast/other, breast/ovarian, Carney, Werner's, Bloom, Li-Fraumeni, xeroderma pigmentosum, ataxia-telangiectasia, osteochondromatosis, retinoblastoma, and MEN2A. PMID:27087812

  14. Characterization of N-acetyltransferase 1 and 2 polymorphisms and haplotype analysis for inflammatory bowel disease and sporadic colorectal carcinoma

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    Cobbs Gary A

    2007-05-01

    Full Text Available Abstract Background N-acetyltransferase 1 (NAT1 and 2 (NAT2 are polymorphic isoenzymes responsible for the metabolism of numerous drugs and carcinogens. Acetylation catalyzed by NAT1 and NAT2 are important in metabolic activation of arylamines to electrophilic intermediates that initiate carcinogenesis. Inflammatory bowel diseases (IBD consist of Crohn's disease (CD and ulcerative colitis (UC, both are associated with increased colorectal cancer (CRC risk. We hypothesized that NAT1 and/or NAT2 polymorphisms contribute to the increased cancer evident in IBD. Methods A case control study was performed with 729 Caucasian participants, 123 CRC, 201 CD, 167 UC, 15 IBD dysplasia/cancer and 223 controls. NAT1 and NAT2 genotyping were performed using Taqman based techniques. Eight single nucleotide polymorphisms (SNPs were characterized for NAT1 and 7 SNPs for NAT2. Haplotype frequencies were estimated using an Expectation-Maximization (EM method. Disease groups were compared to a control group for the frequencies at each individual SNP separately. The same groups were compared for the frequencies of NAT1 and NAT2 haplotypes and deduced NAT2 phenotypes. Results No statistically significant differences were found for any comparison. Strong linkage disequilibrium was present among both the NAT1 SNPs and the NAT2 SNPs. Conclusion This study did not demonstrate an association between NAT1 and NAT2 polymorphisms and IBD or sporadic CRC, although power calculations indicate this study had sufficient sample size to detect differences in frequency as small as 0.05 to 0.15 depending on SNP or haplotype.

  15. Study on specificity of colon carcinoma-associated serum markers and establishment of SVM prediction model

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    Lu Li

    2017-03-01

    Full Text Available We aimed to evaluate the specificity of 12 tumor markers related to colon carcinoma and identify the most sensitive index. Logistic regression and Bhattacharyya distance were used to evaluate the index. Then, different index combinations were used to establish a support vector machine (SVM diagnosis model of malignant colon carcinoma. The accuracy of the model was checked. High accuracy was assumed to indicate the high specificity of the index. Through Logistic regression, three indexes, CEA, HSP60 and CA199, were screened out. Using Bhattacharyya distance, four indexes with the largest Bhattacharyya distance were screened out, including CEA, NSE, AFP, and CA724. The specificity of the combination of the above six indexes was higher than that of other combinations, so did the accuracy of the established SVM identification model. Using Logistic regression and Bhattacharyya distance for detection and establishing an SVM model based on different serum marker combinations can increase diagnostic accuracy, providing a theoretical basis for application of mathematical models in cancer diagnosis.

  16. CT colonography: computer-aided detection of morphologically flat T1 colonic carcinoma

    International Nuclear Information System (INIS)

    Taylor, Stuart A.; Iinuma, Gen; Saito, Yutaka; Zhang, Jie; Halligan, Steve

    2008-01-01

    The purpose was to evaluate the ability of computer-aided detection (CAD) software to detect morphologically flat early colonic carcinoma using CT colonography (CTC). Twenty-four stage T1 colonic carcinomas endoscopically classified as flat (width over twice height) were accrued from patients undergoing staging CTC. Tumor location was annotated by three experienced radiologists in consensus aided by the endosocpic report. CAD software was then applied at three settings of sphericity (0, 0.75, and 1). Computer prompts were categorized as either true positive (overlapping tumour boundary) or false positive. True positives were subclassified as focal or non focal. The 24 cancers were endoscopically classified as type IIa (n=11) and type IIa+IIc (n=13). Mean size (range) was 27 mm (7-70 mm). CAD detected 20 (83.3%), 17 (70.8%), and 13 (54.1%) of the 24 cancers at filter settings of 0, 0.75, and 1, respectively with 3, 4, and 8 missed cancers of type IIa, respectively. The mean total number of false-positive CAD marks per patient at each filter setting was 36.5, 21.1, and 9.5, respectively, excluding polyps. At all settings, >96.1% of CAD true positives were classified as focal. CAD may be effective for the detection of morphologically flat cancer, although minimally raised laterally spreading tumors remain problematic. (orig.)

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

    LENUS (Irish Health Repository)

    Kaballo, Mohammed A

    2011-08-02

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

  18. PARP-1 expression is increased in colon adenoma and carcinoma and correlates with OGG1.

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    Tomasz Dziaman

    Full Text Available The ethiology of colon cancer is largely dependent on inflammation driven oxidative stress. The analysis of 8-oxodeoxyguanosine (8-oxodGuo level in leukocyte DNA of healthy controls (138 individuals, patients with benign adenomas (AD, 137 individuals and with malignant carcinomas (CRC, 169 individuals revealed a significant increase in the level of 8-oxodGuo in leukocyte DNA of AD and CRC patients in comparison to controls. The counteracting mechanism is base excision repair, in which OGG1 and PARP-1 play a key role. We investigated the level of PARP-1 and OGG1 mRNA and protein in diseased and marginal, normal tissues taken from AD and CRC patients and in leukocytes taken from the patients as well as from healthy subjects. In colon tumors the PARP-1 mRNA level was higher than in unaffected colon tissue and in polyp tissues. A high positive correlation was found between PARP-1 and OGG1 mRNA levels in all investigated tissues. This suggests reciprocal influence of PARP-1 and OGG1 on their expression and stability, and may contribute to progression of colon cancer. PARP-1 and OGG1 proteins level was several fold higher in polyps and CRC in comparison to normal colon tissues. Individuals bearing the Cys326Cys genotype of OGG1 were characterized by higher PARP-1 protein level in diseased tissues than the Ser326Cys and Ser326Ser genotypes. Aforementioned result may suggest that the diseased cells with polymorphic OGG1 recruit more PARP protein, which is necessary to remove 8-oxodGuo. Thus, patients with decreased activity of OGG1/polymorphism of the OGG1 gene and higher 8-oxodGuo level may be more susceptible to treatment with PARP-1 inhibitors.

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

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    Mingquan Chen

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

  20. Mutations in ACTRT1 and its enhancer RNA elements lead to aberrant activation of Hedgehog signaling in inherited and sporadic basal cell carcinomas.

    Science.gov (United States)

    Bal, Elodie; Park, Hyun-Sook; Belaid-Choucair, Zakia; Kayserili, Hülya; Naville, Magali; Madrange, Marine; Chiticariu, Elena; Hadj-Rabia, Smail; Cagnard, Nicolas; Kuonen, Francois; Bachmann, Daniel; Huber, Marcel; Le Gall, Cindy; Côté, Francine; Hanein, Sylvain; Rosti, Rasim Özgür; Aslanger, Ayca Dilruba; Waisfisz, Quinten; Bodemer, Christine; Hermine, Olivier; Morice-Picard, Fanny; Labeille, Bruno; Caux, Frédéric; Mazereeuw-Hautier, Juliette; Philip, Nicole; Levy, Nicolas; Taieb, Alain; Avril, Marie-Françoise; Headon, Denis J; Gyapay, Gabor; Magnaldo, Thierry; Fraitag, Sylvie; Crollius, Hugues Roest; Vabres, Pierre; Hohl, Daniel; Munnich, Arnold; Smahi, Asma

    2017-10-01

    Basal cell carcinoma (BCC), the most common human cancer, results from aberrant activation of the Hedgehog signaling pathway. Although most cases of BCC are sporadic, some forms are inherited, such as Bazex-Dupré-Christol syndrome (BDCS)-a cancer-prone genodermatosis with an X-linked, dominant inheritance pattern. We have identified mutations in the ACTRT1 gene, which encodes actin-related protein T1 (ARP-T1), in two of the six families with BDCS that were examined in this study. High-throughput sequencing in the four remaining families identified germline mutations in noncoding sequences surrounding ACTRT1. These mutations were located in transcribed sequences encoding enhancer RNAs (eRNAs) and were shown to impair enhancer activity and ACTRT1 expression. ARP-T1 was found to directly bind to the GLI1 promoter, thus inhibiting GLI1 expression, and loss of ARP-T1 led to activation of the Hedgehog pathway in individuals with BDCS. Moreover, exogenous expression of ACTRT1 reduced the in vitro and in vivo proliferation rates of cell lines with aberrant activation of the Hedgehog signaling pathway. In summary, our study identifies a disease mechanism in BCC involving mutations in regulatory noncoding elements and uncovers the tumor-suppressor properties of ACTRT1.

  1. Lymph node metastasis of carcinomas of transverse colon including flexures. Consideration of the extramesocolic lymph node stations.

    Science.gov (United States)

    Perrakis, Aristotelis; Weber, Klaus; Merkel, Susanne; Matzel, Klaus; Agaimy, Abbas; Gebbert, Carol; Hohenberger, Werner

    2014-10-01

    Complete mesocolic excision (CME) is nowadays state of the art in the treatment of colon cancer. In cases of carcinoma of transverse colon and of both flexures an extramesocolic lymph node metastasis can be found in the infrapancreatic lymph node region (ILR) and across the gastroepiploic arcade (GLR). These direct metastatic routes were not previously systematically considered. In order to validate our hypothesis of these direct metastatic pathways and to obtain evidence of our approach of including dissection of these areas as part of CME, we initiated a prospective study evaluating these lymph node regions during surgery. Forty-five consecutive patients with primary tumour manifestation in transverse colon and both flexures between May 2010 and January 2013 were prospectively analyzed. Patients were followed up for at least 6 months. Mode of surgery, histopathology, morbidity and mortality were evaluated. Twenty-six patients had a carcinoma of transverse colon, 16 patients one of hepatic flexure and four patients one of splenic flexure. The median lymph node yield was 40. Occurrence of lymph node metastasis in ILR was registered in five patients and in GLR in four patients. The mean lymph node ratio was 0.085. Postoperative complications occurred in nine patients, and postoperative mortality was 2 %. We were able to demonstrate this novel metastatic route of carcinomas of the transverse colon and of both flexures in ILR and GLR. These could be considered as regional lymph node regions and have to be included into surgery for cancer of the transverse colon including both flexures.

  2. Evaluation of spiral CT in staging of colon and rectum carcinoma

    International Nuclear Information System (INIS)

    Hundt, W.; Braunschweig, R.; Reiser, M.

    1999-01-01

    The purpose of our study was to evaluate the capability of a subsecond spiral-CT scanner using two contrast medium phases in staging of colorectal cancer. In our study we included 37 patients with proven rectum or colon carcinoma. Spiral CT was performed following tap-water enema of the colon in the arterial and venous phases of contrast medium enhancement. Our results were compared with the findings of pathological examination after surgery. The tumor's size and extension were evaluated in the arterial and venous phases, the lymph nodes in the venous phase of the CT scan. The tumor was in the rectum (n = 14), sigma (n = 11), descending colon (n = 6), and cecum (n = 6). Two-phase spiral CT had a sensitivity of 97.2 % in the arterial phase and 89.1 % in the venous phase in detecting the carcinoma. The staging results were in the arterial phase in 30 of 37 cases (81.0 %) and in the venous phase in 24 of 37 cases (64.8 %) according to pathology. In 27 of 32 patients (84.3 %) lymph nodes were detected. The correct classification of the N-stage was possible in 23 of 34 cases (67.6 %). The combined use of arterial and venous phases in staging of colorectal cancer can improve the T- and N-stage classification in comparison with using only one contrast medium phase. The arterial phase is superior compared with the venous phase for local tumor staging and the venous phase is used for lymph node assessment. (orig.) (orig.)

  3. Paraneoplastic Dermatomyositis in Hepatocellular Carcinoma with Colonic Perforation: A Case Report

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    Naoteru Miyata

    2016-09-01

    Full Text Available Background: Dermatomyositis (DM is an autoimmune disease characterized by cutaneous Gottron papules, heliotrope rash, and proximal myopathy. It may also present as a paraneoplastic syndrome that can complicate a variety of different cancers, such as lung, cervical, and breast cancer. However, the association with hepatocellular carcinoma (HCC is extremely rare. Moreover, to our knowledge, there are no previous reports of colonic perforation following steroid pulse treatment for a DM patient. Case Summary: A 61-year-old male complained of a skin rash that began in his neck and spread to his face and abdomen. On physical examination, the patient was also found to have symmetrical proximal muscle weakness, abdominal pain, heliotrope rash in the periorbital skin, and poikiloderma on his face and abdomen. Serum level of muscle enzymes was remarkably increased. Muscle examination revealed symmetrical proximal weakness. The diagnosis of DM was made, and steroid treatment was started for symptomatic relief. A search for causative malignancy revealed HCC. Despite steroid therapy for DM, his symptoms did not improve. Additionally, C-reactive protein elevation was seen along with severe abdominal pain on day 14 of admission. Shortly after this, the patient died of septic shock due to suppurative peritonitis after perforation of the ascending colon. Conclusion: Here, we present a rare case of DM caused by non-hepatitis-associated advanced HCC with colonic perforation. The cause of colonic perforation is still unclear. This case demonstrates the need to carefully monitor abdominal pain in DM patients as symptoms can be masked by steroid therapy.

  4. Kupffer cells and pit cells are not effective in the defense against experimentally induced colon carcinoma metastasis in rat liver

    NARCIS (Netherlands)

    Griffini, P.; Smorenburg, S. M.; Vogels, I. M.; Tigchelaar, W.; van Noorden, C. J.

    1996-01-01

    The present study was performed to investigate processes involved in circumvention of the immune system by advanced stages of tumor growth in the liver, The efficacy of Kupffer cells and pit cells against cancer cells was tested in vivo in an experimental model of colon carcinoma metastasis in rat

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

    DEFF Research Database (Denmark)

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

    1982-01-01

    A spontaneous change in DNA content of a human colonic carcinoma grown in nude mice was observed fortuitously. The tumor initially had a G1 cell DNA content of 1.3 times that of normal cells. Flow cytometric DNA analysis showed in transplant generation 56 the appearance of a new subpopulation which...

  6. Diets That Promote Colon Inflammation Associate With Risk of Colorectal Carcinomas That Contain Fusobacterium nucleatum.

    Science.gov (United States)

    Liu, Li; Tabung, Fred K; Zhang, Xuehong; Nowak, Jonathan A; Qian, Zhi Rong; Hamada, Tsuyoshi; Nevo, Daniel; Bullman, Susan; Mima, Kosuke; Kosumi, Keisuke; da Silva, Annacarolina; Song, Mingyang; Cao, Yin; Twombly, Tyler S; Shi, Yan; Liu, Hongli; Gu, Mancang; Koh, Hideo; Li, Wanwan; Du, Chunxia; Chen, Yang; Li, Chenxi; Li, Wenbin; Mehta, Raaj S; Wu, Kana; Wang, Molin; Kostic, Aleksander D; Giannakis, Marios; Garrett, Wendy S; Hutthenhower, Curtis; Chan, Andrew T; Fuchs, Charles S; Nishihara, Reiko; Ogino, Shuji; Giovannucci, Edward L

    2018-04-24

    Specific nutritional components are likely to induce intestinal inflammation, which is characterized by increased levels of interleukin 6 (IL6), C-reactive protein (CRP), and TNF receptor superfamily member 1B (TNFRSF1B) in the circulation and promotes colorectal carcinogenesis. The inflammatory effects of a diet can be estimated based on empirical dietary inflammatory pattern (EDIP) score, calculated based on intake of 18 foods associated with plasma levels of IL6, CRP, and TNFRSF1B. An inflammatory environment in the colon (based on increased levels of IL6, CRP, and TNFRSF1B in peripheral blood) contributes to impairment of the mucosal barrier and altered immune cell responses, affecting the composition of the intestinal microbiota. Colonization by Fusobacterium nucleatum has been associated with presence and features of colorectal adenocarcinoma. We investigated the association between diets that promote inflammation (based on EDIP score) and colorectal cancer subtypes classified by level of F nucleatum in the tumor microenvironment. We calculated EDIP scores based on answers to questionnaires collected from participants in the Nurses' Health Study (through June 1, 2012) and the Health Professionals Follow-up Study (through January 31, 2012). Participants in both cohorts reported diagnoses of rectal or colon cancer in biennial questionnaires; deaths from unreported colorectal cancer cases were identified through the National Death Index and next of kin. Colorectal tumor tissues were collected from hospitals where the patients underwent tumor resection and F nucleatum DNA was quantified by a PCR assay. We used multivariable duplication-method Cox proportional hazard regression to assess the associations of EDIP scores with risks of colorectal cancer subclassified by F nucleatum status. During 28 years of follow up of 124,433 participants, we documented 951 incident cases of colorectal carcinoma with tissue F nucleatum data. Higher EDIP scores associated with

  7. A CpG island hypermethylation profile of primary colorectal carcinomas and colon cancer cell lines

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    Rognum Torleiv O

    2004-10-01

    Full Text Available Abstract Background Tumor cell lines are commonly used as experimental tools in cancer research, but their relevance for the in vivo situation is debated. In a series of 11 microsatellite stable (MSS and 9 microsatellite unstable (MSI colon cancer cell lines and primary colon carcinomas (25 MSS and 28 MSI with known ploidy stem line and APC, KRAS, and TP53 mutation status, we analyzed the promoter methylation of the following genes: hMLH1, MGMT, p16INK4a (CDKN2A α-transcript, p14ARF (CDKN2A β-transcript, APC, and E-cadherin (CDH1. We compared the DNA methylation profiles of the cell lines with those of the primary tumors. Finally, we examined if the epigenetic changes were associated with known genetic markers and/or clinicopathological variables. Results The cell lines and primary tumors generally showed similar overall distribution and frequencies of gene methylation. Among the cell lines, 15%, 50%, 75%, 65%, 20% and 15% showed promoter methylation for hMLH1, MGMT, p16INK4a, p14ARF, APC, and E-cadherin, respectively, whereas 21%, 40%, 32%, 38%, 32%, and 40% of the primary tumors were methylated for the same genes. hMLH1 and p14ARF were significantly more often methylated in MSI than in MSS primary tumors, whereas the remaining four genes showed similar methylation frequencies in the two groups. Methylation of p14ARF, which indirectly inactivates TP53, was seen more frequently in tumors with normal TP53 than in mutated samples, but the difference was not statistically significant. Methylation of p14ARF and p16INK4a was often present in the same primary tumors, but association to diploidy, MSI, right-sided location and female gender was only significant for p14ARF. E-cadherin was methylated in 14/34 tumors with altered APC further stimulating WNT signaling. Conclusions The present study shows that colon cancer cell lines are in general relevant in vitro models, comparable with the in vivo situation, as the cell lines display many of the same

  8. [A Case of Endocrine Cell Carcinoma of the Transverse Colon with Very Poor Prognosis, Onset with Bowel Obstruction].

    Science.gov (United States)

    Yabe, Sakiko; Yamamoto, Eisuke; Masuda, Taiki; Sugimoto, Hitoshi; Koshiishi, Haruya; Yoshimura, Tetsunori

    2018-01-01

    We report a case of endocrine cell carcinoma of the colon with very poor prognosis, onset with bowel obstruction and multiple liver metastases. The patient was a 77-year-old man who underwent left hemicolectomy after a colon stent treatment for bowel obstruction due to cancer of the transverse colon with unresectable multiple liver metastases. Chemotherapy was not initiated because of his poor health. He died of primary cancer 52 days after the surgery. Endocrine cell carcinoma of the large intestine has a poor prognosis due to an early onset of liver and lymph node metastases, as well as peritoneal dissemination. A large-scale clinical study is needed to establish an effective adjuvant chemotherapy.

  9. Pathway of deoxynivalenol-induced apoptosis in human colon carcinoma cells

    International Nuclear Information System (INIS)

    Bensassi, Fatma; El Golli-Bennour, Emna; Abid-Essefi, Salwa; Bouaziz, Chayma; Hajlaoui, Mohamed Rabeh; Bacha, Hassen

    2009-01-01

    The mycotoxin, deoxynivalenol (DON), is generally detected in cereal grains and grain-based food products worldwide. Therefore, DON has numerous toxicological effects on animals and humans. The present investigation was conducted to determine the molecular aspects of DON toxicity on human colon carcinoma cells (HT 29). To this aim, we have monitored the effects of DON on (i) cell viability, (ii) Heat shock protein expressions as a parameter of protective and adaptive response, (iii) oxidative damage and (iv) cell death signalling pathway. Our results clearly showed that DON treatment inhibits cell proliferation, did not induce Hsp 70 protein expression and reactive oxygen species generation. We have also demonstrated that this toxin induced a DNA fragmentation followed by p53 and caspase-3 activations. Finally, our findings suggested that oxidative damage is not the major contributor to DON toxicity. This mycotoxin induces direct DNA lesions and could be considered by this fact as a genotoxic agent inducing cell death via an apoptotic process.

  10. Teng-Long-Bu-Zhong-Tang, a Chinese herbal formula, enhances anticancer effects of 5--Fluorouracil in CT26 colon carcinoma.

    Science.gov (United States)

    Deng, Shan; Hu, Bing; An, Hong-Mei; Du, Qin; Xu, Ling; Shen, Ke-Ping; Shi, Xiu-Feng; Wei, Meng-Meng; Wu, Yang

    2013-06-08

    Colorectal cancer remains one of the leading causes of cancer death worldwide. Traditional Chinese Medicine (TCM) has played a positive role in colorectal cancer treatment. There is a great need to establish effective herbal formula for colorectal cancer treatment. Based on TCM principles and clinical practices, we have established an eight herbs composed formula for colorectal cancer treatment, which is Teng-Long-Bu-Zhong-Tang (TLBZT). We have demonstrated the anticancer effects of TLBZT against colorectal carcinoma in vitro. In present study, we evaluated the anticancer potential of TLBZT, used alone or in combination with low dose of 5-Fluorouracil (5-Fu), in CT26 colon carcinoma in vivo. CT26 colon carcinoma was established in BALB/c mice and treated with TLBZT, 5-Fu, or TLBZT plus 5-Fu. The tumor volumes were observed. Apoptosis was detected by TUNEL assay. Caspases activities were detected by colorimetric assay. Cell senescence was indentified by senescence β-galactosidase staining. Gene expression and angiogenesis was observed by immunohistochemistry or western blot. TLBZT significantly inhibited CT26 colon carcinoma growth. TLBZT elicited apoptosis in CT26 colon carcinoma, accompanied by Caspase-3, 8, and 9 activation and PARP cleavage, and downregulation of XIAP and Survivin. TLBZT also induced cell senescence in CT26 colon carcinoma, with concomitant upregulation of p16 and p21 and downregulation of RB phosphorylation. In addition, angiogenesis and VEGF expression in CT26 colon carcinoma was significantly inhibited by TLBZT treatment. Furthermore, TLBZT significantly enhanced anticancer effects of 5-Fu in CT26 colon carcinoma. TLBZT exhibited significantly anticancer effect, and enhanced the effects of 5-Fu in CT26 colon carcinoma, which may correlate with induction of apoptosis and cell senescence, and angiogenesis inhibition. The present study provides new insight into TCM approaches for colon cancer treatment that are worth of further study.

  11. A Rare Case of Colonic Metastases From Tonsillar Carcinoma: Case Report and Review of Literature.

    Science.gov (United States)

    Tariq, Hassan; Kamal, Muhammad Umar; Mehershahi, Shehriyar; Saad, Muhammad; Azam, Sara; Kumar, Kishore; Niazi, Masooma; Makker, Jasbir; Daniel, Myrta

    2018-02-01

    The incidence of tonsillar cancer has increased by four times in the United States over the last few decades likely due to recent increase in human papilloma virus (HPV) infections. The stage of the tumor predicts likelihood of metastasis, with advanced stages associated with higher chances of metastasis. The squamous cell carcinomas (SCCs) of the head and neck commonly metastasize to the lung, bone and liver in descending order. Tonsillar cancer rarely involves the small bowel and our review of the literature did not reveal any reported case of metastasis to the colon/large bowel. Our patient had locally metastatic tonsillar cancer, treated with partial pharyngectomy and selective neck dissection but later developed several bone and colonic metastases concurrently, likely secondary to hematogeneous dissemination after a few months of therapy. To the best of our knowledge, large bowel metastasis from head and neck SCC has never been reported in the literature. In these patients presenting with atypical gastrointestinal symptoms, a high index of suspicion should be maintained to determine the extent of metastasis and identify other metastatic sites.

  12. Metachronous metastasis- and survival-analysis show prognostic importance of lymphadenectomy for colon carcinomas

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    Laubert Tilman

    2012-03-01

    Full Text Available Abstract Background Lymphadenectomy is performed to assess patient prognosis and to prevent metastasizing. Recently, it was questioned whether lymph node metastases were capable of metastasizing and therefore, if lymphadenectomy was still adequate. We evaluated whether the nodal status impacts on the occurrence of distant metastases by analyzing a highly selected cohort of colon cancer patients. Methods 1,395 patients underwent surgery exclusively for colon cancer at the University of Lübeck between 01/1993 and 12/2008. The following exclusion criteria were applied: synchronous metastasis, R1-resection, prior/synchronous second carcinoma, age Results Five-year survival rates for TM + and TM- were 21% and 73%, respectively (p Conclusions Besides a higher T-category, a positive N-stage independently implies a higher probability to develop distant metastases and correlates with poor survival. Our data thus show a prognostic relevance of lymphadenectomy which should therefore be retained until conclusive studies suggest the unimportance of lmyphadenectomy.

  13. p53 is important for the anti-proliferative effect of ibuprofen in colon carcinoma cells

    International Nuclear Information System (INIS)

    Janssen, Astrid; Schiffmann, Susanne; Birod, Kerstin; Maier, Thorsten J.; Wobst, Ivonne; Geisslinger, Gerd; Groesch, Sabine

    2008-01-01

    S-ibuprofen which inhibits the cyclooxygenase-1/-2 and R-ibuprofen which shows no COX-inhibition at therapeutic concentrations have anti-carcinogenic effects in human colon cancer cells; however, the molecular mechanisms for these effects are still unknown. Using HCT-116 colon carcinoma cell lines, expressing either the wild-type form of p53 (HCT-116 p53 wt ) or being p(HCT-116 p53 -/- ), we demonstrated that both induction of a cell cycle block and apoptosis after S- and R-ibuprofen treatment is in part dependent on p53. Also in the in vivo nude mice model HCT-116 p53 -/- xenografts were less sensitive for S- and R-ibuprofen treatment than HCT-116 p53 wt cells. Furthermore, results indicate that induction of apoptosis in HCT-116 p53 wt cells after ibuprofen treatment is in part dependent on a signalling pathway including the neutrophin receptor p75 NTR , p53 and Bax

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

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    Mike Black

    2016-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Pankaj G. Vashi

    2012-07-01

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

  16. Apoptosis inducing activity of benzophenanthridine-type alkaloids and 2-arylbenzofuran neolignans in HCT116 colon carcinoma cells.

    Science.gov (United States)

    Mansoor, Tayyab A; Borralho, Pedro M; Luo, Xuan; Mulhovo, Silva; Rodrigues, Cecília M P; Ferreira, Maria-José U

    2013-07-15

    Thirteen compounds belonging to different classes of alkaloids (1-9) and lignans (10-13), isolated from the methanol extract of roots of the African medicinal plant Zanthoxylum capense, were assayed for their ability as apoptosis inducers in HCT116 colon carcinoma cells. The cytotoxicity of these compounds was evaluated in HCT116 colon carcinoma cells by the MTS assay. Out of the tested compounds, three benzophenanthridine alkaloids (1, 4, and 7), a dibenzyl butyrolactone lignan (10), and two 2-arylbenzofuran neolignans (12 and 13) displayed significant cytotoxicity to HCT116 cells, confirmed by the Guava ViaCount viability assay. The selected compounds (1, 4, 7, 10, 12, and 13) were further tested for apoptosis induction activity in HCT116 cells, by evaluation of nuclear morphology following Hoechst staining, and by caspase-3 like activity assays. Morphologic evaluation of HCT116 nuclei following Hoechst staining and fluorescence microscopy revealed that compounds 1, 4, 7, 10, 12, and 13 induced apoptosis in HCT116 colon carcinoma cells, producing similar, or higher, apoptosis levels when compared with 5-fluorouracil (5-FU), the cornerstone cytotoxic used in colon cancer treatment for several decades. In fact, HCT116 cells developed morphological changes characteristic of apoptosis, including chromatin condensation, nuclear fragmentation and formation of apoptotic bodies. Importantly, compounds 4 and 13 at 20 μM were the most promising in this study, inducing respectively ∼11- and 7-fold increases in apoptotic cells as compared to vehicle control, whereas 5-FU increased apoptosis by ∼2-fold. Apoptosis induction for compounds 4 and 13 was further confirmed by caspase-3-like activity assays, which showed respectively ∼2- and 1.5-fold increases in caspase-3-like activity compared to vehicle control. These results suggested that specific benzophenanthridine alkaloids and 2-arylbenzofuran neolignans isolated from Zanthoxylum capense show strong anticancer

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

    Science.gov (United States)

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

    2014-01-01

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

  18. Clone-specific expression, transcriptional regulation, and action of interleukin-6 in human colon carcinoma cells

    International Nuclear Information System (INIS)

    Brozek, Wolfgang; Bises, Giovanna; Fabjani, Gerhild; Cross, Heide S; Peterlik, Meinrad

    2008-01-01

    Many cancer cells produce interleukin-6 (IL-6), a cytokine that plays a role in growth stimulation, metastasis, and angiogenesis of secondary tumours in a variety of malignancies, including colorectal cancer. Effectiveness of IL-6 in this respect may depend on the quantity of basal and inducible IL-6 expressed as the tumour progresses through stages of malignancy. We therefore have evaluated the effect of IL-6 modulators, i.e. IL-1β, prostaglandin E 2 , 17β-estradiol, and 1,25-dihydroxyvitamin D 3 , on expression and synthesis of the cytokine at different stages of tumour progression. We utilized cultures of the human colon carcinoma cell clones Caco-2/AQ, COGA-1A and COGA-13, all of which expressed differentiation and proliferation markers typical of distinct stages of tumour progression. IL-6 mRNA and protein levels were assayed by RT-PCR and ELISA, respectively. DNA sequencing was utilized to detect polymorphisms in the IL-6 gene promoter. IL-6 mRNA and protein concentrations were low in well and moderately differentiated Caco-2/AQ and COGA-1A cells, but were high in poorly differentiated COGA-13 cells. Addition of IL-1β (5 ng/ml) to a COGA-13 culture raised IL-6 production approximately thousandfold via a prostaglandin-independent mechanism. Addition of 17β-estradiol (10 -7 M) reduced basal IL-6 production by one-third, but IL-1β-inducible IL-6 was unaffected. Search for polymorphisms in the IL-6 promoter revealed the presence of a single haplotype, i.e., -597A/-572G/-174C, in COGA-13 cells, which is associated with a high degree of transcriptional activity of the IL-6 gene. IL-6 blocked differentiation only in Caco-2/AQ cells and stimulated mitosis through up-regulation of c-myc proto-oncogene expression. These effects were inhibited by 10 -8 M 1,25-dihydroxyvitamin D 3 . In human colon carcinoma cells derived from well and moderately differentiated tumours, IL-6 expression is low and only marginally affected, if at all, by PGE 2 , 1,25-dihydroxyvitamin D

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

    Directory of Open Access Journals (Sweden)

    Leanza V

    2013-05-01

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

  20. The Presence of Telomere Fusion in Sporadic Colon Cancer Independently of Disease Stage, TP53/KRAS Mutation Status, Mean Telomere Length, and Telomerase Activity

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    Hiromi Tanaka

    2014-10-01

    Full Text Available Defects in telomere maintenance can result in telomere fusions that likely play a causative role in carcinogenesis by promoting genomic instability. However, this proposition remains to be fully understood in human colon carcinogenesis. In the present study, the temporal sequence of telomere dysfunction dynamics was delineated by analyzing telomere fusion, telomere length, telomerase activity, hotspot mutations in KRAS or BRAF, and TP53 of tissue samples obtained from 18 colon cancer patients. Our results revealed that both the deficiency of p53 and the shortening of mean telomere length were not necessary for producing telomere fusions in colon tissue. In five cases, telomere fusion was observed even in tissue adjacent to cancerous lesions, suggesting that genomic instability is initiated in pathologically non-cancerous lesions. The extent of mean telomere attrition increased with lymph node invasiveness of tumors, implying that mean telomere shortening correlates with colon cancer progression. Telomerase activity was relatively higher in most cancer tissues containing mutation(s in KRAS or BRAF and/or TP53 compared to those without these hotspot mutations, suggesting that telomerase could become fully active at the late stage of colon cancer development. Interestingly, the majority of telomere fusion junctions in colon cancer appeared to be a chromatid-type containing chromosome 7q or 12q. In sum, this meticulous correlative study not only highlights the concept that telomere fusion is present in the early stages of cancer regardless of TP53/KRAS mutation status, mean telomere length, and telomerase activity, but also provides additional insights targeting key telomere fusion junctions which may have significant implications for colon cancer diagnoses.

  1. Clinical procedure for colon carcinoma tissue sampling directly affects the cancer marker-capacity of VEGF family members

    International Nuclear Information System (INIS)

    Pringels, Sarah; Van Damme, Nancy; De Craene, Bram; Pattyn, Piet; Ceelen, Wim; Peeters, Marc; Grooten, Johan

    2012-01-01

    mRNA levels of members of the Vascular Endothelial Growth Factor family (VEGF-A, -B, -C, -D, Placental Growth Factor/PlGF) have been investigated as tissue-based markers of colon cancer. These studies, which used specimens obtained by surgical resection or colonoscopic biopsy, yielded contradictory results. We studied the effect of the sampling method on the marker accuracy of VEGF family members. Comparative RT-qPCR analysis was performed on healthy colon and colon carcinoma samples obtained by biopsy (n = 38) or resection (n = 39) to measure mRNA expression levels of individual VEGF family members. mRNA levels of genes encoding the eicosanoid enzymes cyclooxygenase 2 (COX2) and 5-lipoxygenase (5-LOX) and of genes encoding the hypoxia markers glucose transporter 1 (GLUT-1) and carbonic anhydrase IX (CAIX) were included as markers for cellular stress and hypoxia. Expression levels of COX2, 5-LOX, GLUT-1 and CAIX revealed the occurrence in healthy colon resection samples of hypoxic cellular stress and a concurrent increment of basal expression levels of VEGF family members. This increment abolished differential expression of VEGF-B and VEGF-C in matched carcinoma resection samples and created a surgery-induced underexpression of VEGF-D. VEGF-A and PlGF showed strong overexpression in carcinoma samples regardless of the sampling method. Sampling-induced hypoxia in resection samples but not in biopsy samples affects the marker-reliability of VEGF family members. Therefore, biopsy samples provide a more accurate report on VEGF family mRNA levels. Furthermore, this limited expression analysis proposes VEGF-A and PlGF as reliable, sampling procedure insensitive mRNA-markers for molecular diagnosis of colon cancer

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

    Science.gov (United States)

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

    2010-02-01

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

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

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    Sudipta Das

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

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

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    Anika Schroeter

    2014-12-01

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

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

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    Charlotte Hiroux

    2016-06-01

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

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

    Science.gov (United States)

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

    2005-01-01

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

  7. hGH and GHR expression in large cell neuroendocrine carcinoma of the colon and rectum.

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    Jukić, Zoran; Limani, Rinë; Luci, Lumturije Gashi; Nikić, Vivian; Mijić, August; Tomas, Davor; Krušlin, Božo

    2012-08-01

    Large cell neuroendocrine carcinoma (LCNEC) is an aggressive neoplasm with a low frequency of occurrence in the digestive tract. We present a series of eight patients diagnosed with LCNEC of the colon and rectum. Grossly, tumors were presented as endophytic/ulcerative, annular and polypoid masses, with a gray-white color and necrosis in most cases. Histologically, they were high-grade tumors composed of large cells of organoid, nesting, trabecular, rosette-like and palisading patterns, with a high mitotic rate. Tumors were immunoreactive for neuroendocrine markers, including chromogranin A (2/8), synaptophysin (7/8), and neuron-specific enolase (8/8). Moreover, we analyzed the expression of growth hormone (hGH) and growth hormone receptor (GHR) in colorectal LCNECs and six tumors were immunoreactive for hGH, while five tumors were immunoreactive for GHR. To our knowledge hGH and GHR expression has not been previously analyzed in colorectal LCNEC. Their overexpression suggests a role of hGH and GHR in the development of colorectal LCNEC.

  8. The radio-sensitivity effect of E1A gene transfected by PEI on colon carcinoma cell in vitro

    International Nuclear Information System (INIS)

    Wu Yinxia; Liu Dongfang; Liu Yongbiao; Xu Dongmei; Yao Side; Sheng Kanglong

    2011-01-01

    As a neotype nonviral vector, (Polyethylenimine, PEI) has been studied in gene transfection experiment. This study was investigated the growth inhibition and radio-sensitizing effect of E1A gene transfected by PEI on human colon carcinoma cell in vitro. The PSV-E1A recombinant plasmid, which was designed for high-level expression of E1A gene in a variety of eukaryotic cell lines, was transfected into SW480 cells by PEI. The transfection was confirmed by RT-PCR and G418 was used to get colon carcinoma cells stably expressed E1A gene. The cell growth curve were investigated to observe the growth inhibition induced by E1A gene. The redistributions of cell cycle were analyzed by flow cytometry. Cells before and after transfection were treated with irradiation, then the changes of radiation-sensitivity were tested by MTT assay after 24 h meanwhile the expression of HER-2 gene in SW480 cells before and after transfection was detected by western-blot. As results, (1) the colon carcinoma cells expressed E1A gene was confirmed by G418. (2) The result of RT-PCR demonstrated that PEI could transfect plasmid psv-E1A and the cells could stably express E1A gene. (3) Flow cytometry revealed that E1A gene transfected into human colon carcinoma cell could induce S stage suppression (p<0.001) and G2/M stage arrest (p<0.001). (4) Compared with the Non-transfected cells, the E1A-transfected cells (SW480-E1A cells) grew slowly observed by MTT assay which was used to get the absorbance of SW480 cell and SW480-E1A cell. (5) The radiation-sensitivity of SW480 cells transfected with E1A gene was up-regulated obviously (p<0.001). (6) The E1A gene obviously down-regulated HER-2 protein expression in colon carcinoma cells. Anyway, PEI can transfect plasmid psv-E1A gene which can significantly inhibit the growth rate of SW480 cell. Moreover, it also obviously enhanced the cell sensitivity to irradiation. (authors)

  9. Loss of CDX2 Expression and Microsatellite Instability Are Prominent Features of Large Cell Minimally Differentiated Carcinomas of the Colon

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    Hinoi, Takao; Tani, Masachika; Lucas, Peter C.; Caca, Karel; Dunn, Rodney L.; Macri¶, Ettore; Loda¶, Massimo; Appelman, Henry D.; Cho, Kathleen R.; Fearon, Eric R.

    2001-01-01

    Most large bowel cancers are moderately to well-differentiated adenocarcinomas comprised chiefly or entirely of glands lined by tall columnar cells. We have identified a subset of poorly differentiated colon carcinomas with a distinctive histopathological appearance that we term large cell minimally differentiated carcinomas (LCMDCs). These tumors likely include a group of poorly differentiated carcinomas previously described by others as medullary adenocarcinomas. To better understand the pathogenesis of these uncommon neoplasms, we compared molecular features of 15 LCMDCs to those present in 25 differentiated adenocarcinomas (DACs) of the colon. Tumors were examined for alterations commonly seen in typical colorectal carcinomas, including increased p53 and β-catenin immunoreactivity, K-ras gene mutations, microsatellite instability, and loss of heterozygosity of markers on chromosomes 5q, 17p, and 18q. In addition, tumors were evaluated by immunohistochemistry for CDX2, a homeobox protein whose expression in normal adult tissues is restricted to intestinal and colonic epithelium. Markedly reduced or absent CDX2 expression was noted in 13 of 15 (87%) LCMDCs, whereas only 1 of the 25 (4%) DACs showed reduced CDX2 expression (P < 0.001). Nine of 15 (60%) LCMDCs had the high-frequency microsatellite instability phenotype, but only 2 of 25 (8%) DACs had the high-frequency microsatellite instability phenotype (P = 0.002). Our findings provide support for the hypothesis that the molecular pathogenesis of LCMDCs is distinct from that of most DACs. CDX2 alterations and DNA mismatch repair defects have particularly prominent roles in the development of LCMDCs. PMID:11733373

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

    International Nuclear Information System (INIS)

    Zitta, Karina; Meybohm, Patrick; Bein, Berthold; Huang, Ying; Heinrich, Christin; Scholz, Jens; Steinfath, Markus; Albrecht, Martin

    2012-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-04-15

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

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

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    L. Fernández de Bobadilla

    2004-06-01

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

  13. NK-cell-dependent killing of colon carcinoma cells is mediated by natural cytotoxicity receptors (NCRs) and stimulated by parvovirus infection of target cells

    International Nuclear Information System (INIS)

    Bhat, Rauf; Rommelaere, Jean

    2013-01-01

    Investigating how the immune system functions during malignancies is crucial to developing novel therapeutic strategies. Natural killer (NK) cells, an important component of the innate immune system, play a vital role in immune defense against tumors and virus-infected cells. The poor survival rate in colon cancer makes it particularly important to develop novel therapeutic strategies. Oncolytic viruses, in addition to lysing tumor cells, may have the potential to augment antitumor immune responses. In the present study, we investigate the role of NK cells and how parvovirus H-1PV can modulate NK-cell mediated immune responses against colon carcinoma. Human NK cells were isolated from the blood of healthy donors. The cytotoxicity and antibody-mediated inhibition of NK cells were measured in chromium release assays. Phenotypic assessment of colon cancer and dendritic cells was done by FACS. The statistical significance of the results was calculated with Student’s t test (*p <0.05; **, p < 0.01; ***, p < 0.001). We show that IL-2-activated human NK cells can effectively kill colon carcinoma cells. Killing of colon carcinoma cells by NK cells was further enhanced upon infection of the former cells with parvovirus H-1PV. H-1PV has potent oncolytic activity against various tumors, yet its direct killing effect on colon carcinoma cells is limited. The cytotoxicity of NK cells towards colon carcinoma cells, both mock- and H-1PV-infected, was found to be mostly mediated by a combination of natural cytotoxicity receptors (NCRs), namely NKp30, 44, and 46. Colon carcinoma cells displayed low to moderate expression of NK cell ligands, and this expression was modulated upon H-1PV infection. Lysates of H-1PV-infected colon carcinoma cells were found to increase MHC class II expression on dendritic cells. Altogether, these data suggest that IL-2-activated NK cells actively kill colon carcinoma cells and that this killing is mediated by several natural cytotoxicity receptors

  14. Injuries of the sigmoid colon following radiation therapy for carcinoma of the uterine cervix

    International Nuclear Information System (INIS)

    Okuhata, Yoshitaka; Yasukochi, Hiroshi; Sugiyama, Takeo; Toya, Hideki; Tanibe, Masahiro; Koga, Masahisa; Shirato, Makoto; Kuniyasu, Yoshio

    1990-01-01

    Grade 2 or 3 injuries of the sigmoid colon were observed in 4 of 42 patients with carcinoma of the uterine cervix who were treated by radiation therapy. The irradiation was planned as the combination of the external irradiation (whole pelvic 30 Gy and 20 Gy with central shielding by 25 fractions, 5 weeks) and the intracavitary irradiation (RALS, 19 Gy at point A by 3 fractions). To analyze the causes of the radiation sigmoiditis, we have investigated the following factors: age, dose at point A, dose at point C, grade of tandem dislocation, uterine angle, obesity score, evidence of previous surgery to the pelvic cavity and hypertension. The dose at point C and the grade of tandem dislocation were determined from the confirming X-Ps at RALS therapy and external irradiation. The superimposition of these films was performed with corrections for the angle between the projection direction of the X-Ps and the vertical magnification factor of the central shielding area. Point C was defined as a point 2 cm anterior to the intersection of the tandem axis and a curvilinear line 1 cm outside from the margin of central shield on the X-Ps. Grades of tandem disclocation were decided as the number of tandem tips outside of the central shielding area on X-Ps. The doses at point C showed very high statistical significance (p<0.001) with the evidence of radiation sigmoiditis. All the cases with radiation sigmoiditis received over 1290 cGy at point C. Age had also some significance (p<0.05) with radiation sigmoiditis. Other factors showed no significant relationship. Among the patients receiving more than 1280 cGy at point C, injury free cases had over 30% obesity score except for one case. This exceptional patient had 12% obesity score and was in special condition of hydrometra. In conclusion, the dose at point C will be an index of injuries of the sigmoid colon following radiation therapy, and obesity score and condition of the uterus seem to be additional factors. (J.P.N.)

  15. Coffee reduces KRAS expression in Caco-2 human colon carcinoma cells via regulation of miRNAs.

    Science.gov (United States)

    Nakayama, Takuya; Funakoshi-Tago, Megumi; Tamura, Hiroomi

    2017-07-01

    Previous epidemiological studies have demonstrated that moderate coffee consumption is associated with a lower risk of certain types of cancer, particularly colon cancer. To elucidate the molecular basis for this protective action, the effect of coffee on Caco-2 human colon carcinoma cells was investigated. Low concentrations of coffee (Caco-2 cells without affecting cell viability. Coffee also reduced KRAS proto-oncogene, GTPase (KRAS) gene expression in a dose-dependent manner; however, caffeine, caffeic acid and chlorogenic acid, three major constituents of coffee, did not exhibit this effect. Increasing the duration of coffee bean roasting increased the reduction in KRAS expression, suggesting that the active constituents responsible for this effect emerged during the roasting process. MicroRNA (miR) analysis revealed that coffee induced the expression of miR-30c and miR-96, both of which target the KRAS gene. The results of the present study suggested that daily coffee consumption may reduce KRAS activity, thereby preventing the malignant growth of colon carcinoma cells.

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

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    Gabi Dumitrescu

    2017-05-01

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

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

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    Drosten Christian

    2008-11-01

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

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

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    Silvia Mannucci

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

  19. Cytotoxic effects of some animal and vegetable extracts and some chemicals on liver and colon carcinoma and myosarcoma

    International Nuclear Information System (INIS)

    Bayazit, Vahdettin

    2004-01-01

    To study, the cytotoxic effects of some biological and chemical agents on G, S, G, M and G phases of liver and colon carcinomas and myosarcoma cells obtained with chemical carcinogens dimethylbenzanthracene (Dmba) and cadmium chloride. Eight rabbit livers, colon carcinoma and myosarcoma cell lines were obtained by injection of Dmba in the Biology Laboratory, of the University of Dumlupinar, Kutahya, Turkey between January 2001 and June 2003. All lines were grown at 37degrees celsius and 5% carbon dioxide in sterile RPMI-1640 medium with 10% fetal bovine serum after addition of glutamate, penicillin (50 units/ml) and streptomycin (50 ug/ml) (complete medium). Cells were grown on standard tissue culture plastic flasks to 80% confluence and passed by trypsinization. Tortoise (Testudo graeca) shell, sponge (Geodia cydonium), medusa (Aurelia aurita), meat flies (Calliphora erythrocephala) larva, frog (Rana ridibunda) larva and juniper (Juniperus communis) berry extracts killed a large amount of the liver and colon carcinomas and the myosarcoma cells in G2, M and G0 phases (p<0.01). The mistletoe (Viscum album) extract had more effect in only the G0 phase (p<0.05). Genistein, genistin, glycitein, glycitin, daitzein and daitzin have significantly decreased in the cancer cells tests, particularly, genistein and daitzein caused the apoptotic effect in G2, M and G0 phases (p<0.01). Cesium chloride, a mixture of cesium chloride with magnesium chloride had the most effect on tumor cells (p<0.01). AzhexSi, Azhex-AzhepSi, Et-Azhex-AzhepSi, AzhepSi, Hexamine and DL 54 have been inhibited in various levels of the cancer cells (p<0.05, p<0.01). This data suggest that some biological extracts and chemicals tested may be useful chemotherapeutic agents to inhibit the growth of cancer cells. This study sheds some light for new anti cancerogenic experiments preventing various cancers on humans. (author)

  20. Colonic healing: the effect of irradiation and chemotherapy - an experimental study, resembling adjuvant therapy for colorectal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Weiber, S.

    1993-08-01

    Adjuvant treatment of colon and rectal carcinoma is of major interest. Irradiation and chemotherapy are modalities used widely. The purpose of this study was to evaluate the effect of preoperative irradiation and postoperative intraperitoneal 5-fluorouracil treatment on colonic healing. In rats preoperative irradiation of the lower abdominal region by 10 + 10 Gy four days apart caused inflammatory reaction in the colon as evaluated by histology and determination of myeloperoxidase activity. The inflammatory reaction reached its peek within a week of the second irradiation. When standard used colonic resections and anastomes were performed within the irradiate part of the colon the anastomotic healing was not affected during the first week after operation as judged by complications and breaking strength. A lower breaking strength and an increase in myeloperoxidase activity two months after operation may indicate late changes within the intestinal wall. Intraperitoneal 5-fluorouracil in rat given immediately after colonic resection and repeated as daily injections caused a weight loss and marked reduction in breaking strength of the anastomosis as well as in the abdominal skin wound. A reduction in 5-fluorouracil concentration did not alter the negative wound healing effect of the chemotherapy. In a group of rats subjected to nutritional depletion, mimicking the weight curve of 5-fluorouracil treated animals, anastomotic breaking strength was not compromised to the same extent as when 5-fluorouracil was given. This indicated a direct toxic effect rather than an effect of reduced food intake caused by 5-FU treatment. Collagen synthesis and the formation of new tissue in the wound gap was reduced in 5-fluorouracil treated animals compared to controls as judged by in vivo incorporation of {sup 3}H-proline in the anastomotic segment and determination of anastomotic breaking strength after removal of sutures. 108 refs.

  1. Colonic healing: the effect of irradiation and chemotherapy - an experimental study, resembling adjuvant therapy for colorectal carcinoma

    International Nuclear Information System (INIS)

    Weiber, S.

    1993-08-01

    Adjuvant treatment of colon and rectal carcinoma is of major interest. Irradiation and chemotherapy are modalities used widely. The purpose of this study was to evaluate the effect of preoperative irradiation and postoperative intraperitoneal 5-fluorouracil treatment on colonic healing. In rats preoperative irradiation of the lower abdominal region by 10 + 10 Gy four days apart caused inflammatory reaction in the colon as evaluated by histology and determination of myeloperoxidase activity. The inflammatory reaction reached its peek within a week of the second irradiation. When standard used colonic resections and anastomes were performed within the irradiate part of the colon the anastomotic healing was not affected during the first week after operation as judged by complications and breaking strength. A lower breaking strength and an increase in myeloperoxidase activity two months after operation may indicate late changes within the intestinal wall. Intraperitoneal 5-fluorouracil in rat given immediately after colonic resection and repeated as daily injections caused a weight loss and marked reduction in breaking strength of the anastomosis as well as in the abdominal skin wound. A reduction in 5-fluorouracil concentration did not alter the negative wound healing effect of the chemotherapy. In a group of rats subjected to nutritional depletion, mimicking the weight curve of 5-fluorouracil treated animals, anastomotic breaking strength was not compromised to the same extent as when 5-fluorouracil was given. This indicated a direct toxic effect rather than an effect of reduced food intake caused by 5-FU treatment. Collagen synthesis and the formation of new tissue in the wound gap was reduced in 5-fluorouracil treated animals compared to controls as judged by in vivo incorporation of 3 H-proline in the anastomotic segment and determination of anastomotic breaking strength after removal of sutures. 108 refs

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

    DEFF Research Database (Denmark)

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

    2001-01-01

    We present a case of synchronous breast and colon carcinoma in a pleural effusion, to our knowledge the first such reported case in the English-language literature. The patient was a 55-yr-old white female with known metastatic breast and colon carcinoma who developed a malignant pleural effusion...

  3. Curcumin Conjugated with PLGA Potentiates Sustainability, Anti-Proliferative Activity and Apoptosis in Human Colon Carcinoma Cells

    Science.gov (United States)

    Waghela, Bhargav N.; Sharma, Anupama; Dhumale, Suhashini; Pandey, Shashibahl M.; Pathak, Chandramani

    2015-01-01

    Curcumin, an ingredient of turmeric, exhibits a variety of biological activities such as anti-inflammatory, anti-atherosclerotic, anti-proliferative, anti-oxidant, anti-cancer and anti-metastatic. It is a highly pleiotropic molecule that inhibits cell proliferation and induces apoptosis in cancer cells. Despite its imperative biological activities, chemical instability, photo-instability and poor bioavailability limits its utilization as an effective therapeutic agent. Therefore, enhancing the bioavailability of curcumin may improve its therapeutic index for clinical setting. In the present study, we have conjugated curcumin with a biodegradable polymer Poly (D, L-lactic-co-glycolic acid) and evaluated its apoptotic potential in human colon carcinoma cells (HCT 116). The results show that curcumin-PLGA conjugate efficiently inhibits cell proliferation and cell survival in human colon carcinoma cells as compared to native curcumin. Additionally, curcumin conjugated with PLGA shows improved cellular uptake and exhibits controlled release at physiological pH as compared to native curcumin. The curcumin-PLGA conjugate efficiently activates the cascade of caspases and promotes intrinsic apoptotic signaling. Thus, the results suggest that conjugation potentiates the sustainability, anti-proliferative and apoptotic activity of curcumin. This approach could be a promising strategy to improve the therapeutic index of cancer therapy. PMID:25692854

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

    DEFF Research Database (Denmark)

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

    1982-01-01

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

  5. Inhibition of Colon Carcinoma Cell Migration Following Treatment with Purified Venom from Lesser Weever Fish (Trachinus Vipera

    Directory of Open Access Journals (Sweden)

    Myriam Fezai

    2017-04-01

    Full Text Available Background: Injury by the sting of Lesser weever fish (Trachinus vipera may lead to severe pain, edema or tissue necrosis. Cellular effects of the venom are still incompletely understood. Previous observations revealed that purified Lesser weever fish venom (LWFV induces suicidal death of erythrocytes and HCT116 human colon carcinoma cells. The present study addressed the effect of the venom on colon carcinoma cell toxicity, shape and migration both in p53+/+ and/or p53-/- conditions. Methods: Cells were exposed to medium without or with 500 µg/ ml LWFV. Cell shape, cell area and circularity were visualized and quantified by fluorescence microscopy. Cell volume, granularity and cells toxicity were assessed via the apoptotic parameters dissipation of mitochondrial inner transmembrane potential, phosphatidylserine surface exposure and cell membrane permeabilization were measured utilizing flow cytometry. Cell migration was evaluated using wound healing assay and two-dimensional migration assay. Results: LWFV treatment was followed by a marked change of cell shape and size, significant decrease of cell area and circularity, significant impairment of cell migration, as well as induction of apoptosis after long exposition. Conclusions: LWFV exposure leads to cell shrinkage, increased granularity, apoptosis and impairment of cell migration, effects presumably contributing to LWFV-induced tissue injury.

  6. Role of the p53/p21 system in the response of human colon carcinoma cells to Doxorubicin

    Directory of Open Access Journals (Sweden)

    Passarelli Laura

    2004-12-01

    Full Text Available Abstract Background Colon adenocarcinomas are refractory to a number of widely used anticancer agents. Multifactorial mechanisms have been implicated in this intrinsically resistant phenotype, including deregulation of cell death pathways. In this regard, the p53 protein has a well established role in the control of tumor cell response to DNA damaging agents; however, the relationship between p53-driven genes and drug sensitivity remains controversial. The present study investigates the role of the p53/p21 system in the response of human colon carcinoma cells to treatment with the cytotoxic agent doxorubicin (DOX and the possibility to modify the therapeutic index of DOX by modulation of p53 and/or p21 protein levels. Methods The relationship between p53 and p21 protein levels and the cytotoxic effect of DOX was investigated, by MTT assay and western blot analysis, in HCT116 (p53-positive and HT29 (p53-negative colon cancer cells. We then assessed the effects of DOX in two isogenic cell lines derived from HCT116 by abrogating the expression and/or function of p53 and p21 (HCT116-E6 and HCT116 p21-/-, respectively. Finally, we evaluated the effect of pre-treatment with the piperidine nitroxide Tempol (TPL, an agent that was reported to induce p21 expression irrespective of p53 status, on the cytotoxicity of DOX in the four cell lines. Comparisons of IC50 values and apoptotic cell percentages were performed by ANOVA and Bonferroni's test for independent samples. C.I. calculations were performed by the combination Index method. Results Our results indicate that, in the colon carcinoma cell lines tested, sensitivity to DOX is associated with p21 upregulation upon drug exposure, and DOX cytotoxicity is potentiated by pre-treatment with TPL, but only in those cell lines in which p21 can be upregulated. Conclusions p21 induction may significantly contribute to the response of colon adenocarcinomas cells to DOX treatment; and small molecules that can

  7. Mutations in the RET proto-oncogene in sporadic pheochromocytomas

    Energy Technology Data Exchange (ETDEWEB)

    Thibodeau, S.N.; Lindor, N.M.; Honchel, R. [Mayo Clinic and Foundation, Rochester, MN (United States)] [and others

    1994-09-01

    Mutations in the RET proto-oncogene have recently been demonstrated in kindreds with Multiple Endocrine Neoplasia (MEN) types 2A and 2B. Both of these autosomal dominant disorders are characterized by the development of neoplasia in cell lines of neural crest origin, such as medullary throid carcinomas and pheochromocytomas. Individuals with MEN 2B have, in addition, ganglioneuromas of the lips, tongue and colon, a marfanoid habitus, and corneal nerve thickening. Approximately 90% of patients with MEN 2A have a germline mutation in exons 10 or 11, while 95% of patients with MEN 2B have a T{yields}C transition in codon 918 of exon 16. In this study, pheochromocytomas from 29 individuals who had no clinical evidence of MEN 2A or 2B (sporadic) were examined for the presence of either germline or somatic mutations in exons 10, 11, and 16 of the RET proto-oncogene. Of the 29 tumors examined, 3 (10%) were found to have a mutation in one of the three exons. One tumor had a G{yields}A transition in codon 609 (exon 10), another had a 6 bp deletion encompassing codons 632 & 633 (exon 11), and the final tumor had a T{yields}C transition in codon 918 (exon 16). These mutations were not found in the corresponding normal DNA from these individuals, indicating that the mutation were somatic in origin. Although we cannot exclude the possibility of mutations in other regions of the RET proto-oncogene, our data suggests that: (1) individuals presenting with apparently sporadic pheochromocytomas are not likely to have undiagnosed MEN 2A or 2B; and (2) somatic mutations in the RET proto-oncogene contribute to the process of tumorigenesis in a small percentage of sporadic pheochromocytomas.

  8. Expression of DIAPH1 is up-regulated in colorectal cancer and its down-regulation strongly reduces the metastatic capacity of colon carcinoma cells.

    Science.gov (United States)

    Lin, Yuan-Na; Izbicki, Jakob R; König, Alexandra; Habermann, Jens K; Blechner, Christine; Lange, Tobias; Schumacher, Udo; Windhorst, Sabine

    2014-04-01

    In most cases, metastatic colorectal cancer is not curable, thus new approaches are necessary to identify novel targets for colorectal cancer therapy. Actin-binding-proteins (ABPs) directly regulate motility of metastasising tumor cells, and for cortactin an association with colon cancer metastasis has been already shown. However, as its depletion only incompletely inhibits metastasis, additional, more suitable cellular targets have to be identified. Here we analyzed expression of the ABPs, DIAPH1, VASP, N-WASP, and fascin in comparison with cortactin and found that, besides cortactin, DIAPH1 was expressed with the highest frequency (63%) in colorectal cancer. As well as cortactin, DIAPH1 was not detectable in normal colon tissue and expression of both proteins was positively correlated with metastasis of colorectal cancer. To analyse the mechanistic role of DIAPH1 for metastasis of colon carcinoma cells in comparison with cortactin, expression of the proteins was stably down-regulated in the human colon carcinoma cell lines HT-29, HROC-24 and HCT-116. Analysis of metastasis of colon carcinoma cells in SCID mice revealed that depletion of DIAPH1 reduced metastasis 60-fold and depletion of cortactin 16-fold as compared with control cells. Most likely the stronger effect of DIAPH1 depletion on colon cancer metastasis is due to the fact that in vitro knock down of DIAPH1 impaired all steps of metastasis; adhesion, invasion and migration while down-regulation of cortactin only reduced adhesion and invasion. This very strong reducing effect of DIAPH1 depletion on colon carcinoma cell metastasis makes the protein a promising therapeutic target for individualized colorectal cancer therapy. © 2013 UICC.

  9. Transplantation of colon carcinoma into granulation tissue induces an invasive morphotype

    NARCIS (Netherlands)

    Dingemans, K. P.; Zeeman-Boeschoten, I. M.; Keep, R. F.; Das, P. K.

    1993-01-01

    The stroma surrounding many malignant tumors resembles granulation tissue. To test the hypothesis that such stroma stimulates tumor invasiveness, we compared, by electron microscopy and immunohistochemistry, the growth patterns of CC531 rat colon adenocarcinoma in 2 experimental situations: (i)

  10. Infective endocarditis from Streptococcus viridans associated with colonic carcinoma: a case report.

    Science.gov (United States)

    Lin, Chih-Yuan; Chao, Pei-Chieh; Hong, Gou-Jieng; Tsai, Yi-Ting; Lee, Chung-Yi; Tsai, Chien-Sung

    2008-01-01

    Streptococcal bacteremia is an uncommon presentation for colorectal malignancy, yet most physicians would probably be aware of the association between Streptococcus bovis infection and such malignancy; however, many physicians may be unaware that other streptococcal species are also associated with colon and rectal cancers. We describe a 62-year-old male with adenocarcinoma of the sigmoid colon with the presentation of infective endocarditis due to infection by Streptococcus viridans, and we also report on the condition's successful treatment.

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

    Science.gov (United States)

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

    2016-01-01

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

  12. [A case of carcinoma arising in a diverticulum of the transverse colon].

    Science.gov (United States)

    Nomi, Masako; Umemoto, Satoshi; Kikutake, Takashi; Hosaka, Seiji; Mase, Takahiro; Kawamoto, Shunji; Yoshida, Takahisa

    2014-11-01

    A 64 year-old woman presented with advanced, transverse colon cancer arising in the diverticulum. Tumor invasion extended beyond the serosa to the anal side of the colon. Anemia and fatigue progressed after 6 months of iron administration. The hemoglobin value was 5.3 g/dL and carcinoembryonic antigen (CEA) level was elevated to 44.2 ng/mL. A palpable and tender fist-sized mass was found in the right upper abdomen. Computed tomography (CT) revealed a low-density mass in the transverse colon invading beyond the serosa to the anal side of the colon. Right hemi-colectomy with lymph node dissection was performed. The resected specimen contained multiple diverticula including the one from which the tumor arose. Histological examination revealed a well-differentiated, tubular adenocarcinoma (UICC TNM T4bN0M0) arising in a transverse colon diverticulum. There has been no recurrence for 2 years. Colon cancer arising in a diverticulum may expand to the extra-serosa and easily invade to the adjacent organ. In such cases, malignancy should be considered.

  13. Assessment of a novel VEGF targeted agent using patient-derived tumor tissue xenograft models of colon carcinoma with lymphatic and hepatic metastases.

    Directory of Open Access Journals (Sweden)

    Ketao Jin

    Full Text Available The lack of appropriate tumor models of primary tumors and corresponding metastases that can reliably predict for response to anticancer agents remains a major deficiency in the clinical practice of cancer therapy. It was the aim of our study to establish patient-derived tumor tissue (PDTT xenograft models of colon carcinoma with lymphatic and hepatic metastases useful for testing of novel molecularly targeted agents. PDTT of primary colon carcinoma, lymphatic and hepatic metastases were used to create xenograft models. Hematoxylin and eosin staining, immunohistochemical staining, genome-wide gene expression analysis, pyrosequencing, qRT-PCR, and western blotting were used to determine the biological stability of the xenografts during serial transplantation compared with the original tumor tissues. Early passages of the PDTT xenograft models of primary colon carcinoma, lymphatic and hepatic metastases revealed a high degree of similarity with the original clinical tumor samples with regard to histology, immunohistochemistry, genes expression, and mutation status as well as mRNA expression. After we have ascertained that these xenografts models retained similar histopathological features and molecular signatures as the original tumors, drug sensitivities of the xenografts to a novel VEGF targeted agent, FP3 was evaluated. In this study, PDTT xenograft models of colon carcinoma with lymphatic and hepatic metastasis have been successfully established. They provide appropriate models for testing of novel molecularly targeted agents.

  14. Regorafenib effects on human colon carcinoma xenografts monitored by dynamic contrast-enhanced computed tomography with immunohistochemical validation.

    Directory of Open Access Journals (Sweden)

    Clemens C Cyran

    Full Text Available To investigate dynamic contrast-enhanced computed tomography for monitoring the effects of regorafenib on experimental colon carcinomas in rats by quantitative assessments of tumor microcirculation parameters with immunohistochemical validation.Colon carcinoma xenografts (HT-29 implanted subcutaneously in female athymic rats (n = 15 were imaged at baseline and after a one-week treatment with regorafenib by dynamic contrast-enhanced computed tomography (128-slice dual-source computed tomography. The therapy group (n = 7 received regorafenib daily (10 mg/kg bodyweight. Quantitative parameters of tumor microcirculation (plasma flow, mL/100 mL/min, endothelial permeability (PS, mL/100 mL/min, and tumor vascularity (plasma volume, % were calculated using a 2-compartment uptake model. Dynamic contrast-enhanced computed tomography parameters were validated with immunohistochemical assessments of tumor microvascular density (CD-31, tumor cell apoptosis (TUNEL, and proliferation (Ki-67.Regorafenib suppressed tumor vascularity (15.7±5.3 to 5.5±3.5%; p<0.05 and tumor perfusion (12.8±2.3 to 8.8±2.9 mL/100 mL/min; p = 0.063. Significantly lower microvascular density was observed in the therapy group (CD-31; 48±10 vs. 113±25, p<0.05. In regorafenib-treated tumors, significantly more apoptotic cells (TUNEL; 11844±2927 vs. 5097±3463, p<0.05 were observed. Dynamic contrast-enhanced computed tomography tumor perfusion and tumor vascularity correlated significantly (p<0.05 with microvascular density (CD-31; r = 0.84 and 0.66 and inversely with apoptosis (TUNEL; r = -0.66 and -0.71.Regorafenib significantly suppressed tumor vascularity (plasma volume quantified by dynamic contrast-enhanced computed tomography in experimental colon carcinomas in rats with good-to-moderate correlations to an immunohistochemical gold standard. Tumor response biomarkers assessed by dynamic contrast-enhanced computed tomography may be a promising future

  15. First evaluation of the biologic effectiveness factors of boron neutron capture therapy (BNCT) in a human colon carcinoma cell line.

    Science.gov (United States)

    Dagrosa, Maria Alejandra; Crivello, Martín; Perona, Marina; Thorp, Silvia; Santa Cruz, Gustavo Alberto; Pozzi, Emiliano; Casal, Mariana; Thomasz, Lisa; Cabrini, Romulo; Kahl, Steven; Juvenal, Guillermo Juan; Pisarev, Mario Alberto

    2011-01-01

    DNA lesions produced by boron neutron capture therapy (BNCT) and those produced by gamma radiation in a colon carcinoma cell line were analyzed. We have also derived the relative biologic effectiveness factor (RBE) of the neutron beam of the RA-3- Argentine nuclear reactor, and the compound biologic effectiveness (CBE) values for p-boronophenylalanine ((10)BPA) and for 2,4-bis (α,β-dihydroxyethyl)-deutero-porphyrin IX ((10)BOPP). Exponentially growing human colon carcinoma cells (ARO81-1) were distributed into the following groups: (1) BPA (10 ppm (10)B) + neutrons, (2) BOPP (10 ppm (10)B) + neutrons, (3) neutrons alone, and (4) gamma rays ((60)Co source at 1 Gy/min dose-rate). Different irradiation times were used to obtain total absorbed doses between 0.3 and 5 Gy (±10%) (thermal neutrons flux = 7.5 10(9) n/cm(2) sec). The frequency of micronucleated binucleated cells and the number of micronuclei per micronucleated binucleated cells showed a dose-dependent increase until approximately 2 Gy. The response to gamma rays was significantly lower than the response to the other treatments (p irradiations with neutrons alone and neutrons + BOPP showed curves that did not differ significantly from, and showed less DNA damage than, irradiation with neutrons + BPA. A decrease in the surviving fraction measured by 3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazolium bromide (MTT) assay as a function of the absorbed dose was observed for all the treatments. The RBE and CBE factors calculated from cytokinesis block micronucleus (CBMN) and MTT assays were, respectively, the following: beam RBE: 4.4 ± 1.1 and 2.4 ± 0.6; CBE for BOPP: 8.0 ± 2.2 and 2.0 ± 1; CBE for BPA: 19.6 ± 3.7 and 3.5 ± 1.3. BNCT and gamma irradiations showed different genotoxic patterns. To our knowledge, these values represent the first experimental ones obtained for the RA-3 in a biologic model and could be useful for future experimental studies for the application of BNCT to colon carcinoma

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

    Directory of Open Access Journals (Sweden)

    Feiyan Liu

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

  17. Colon interposition

    International Nuclear Information System (INIS)

    Isolauri, J.; Tampere Univ. Central Hospital; Paakkala, T.; Arajaervi, P.; Markkula, H.

    1987-01-01

    Colon interposition was carried out in 12 patients with oesophageal carcinoma and on 38 patients with benign oesophageal disease an average of 71 months before the radiographic examination. Various ischaemic changes including 'jejunization', loss of haustration and stricture formation were observed in 15 cases. In 12 patients one or several diverticula were seen in the colon graft. Reflux was observed in 17 cases in supine position. Double contrast technique in the examination of interposed colon is recommended. (orig.)

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

    Directory of Open Access Journals (Sweden)

    Li Jing

    2011-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Ameneh Sazgarnia

    2009-12-01

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

  20. Sixth nerve palsy as the presenting symptom of metastatic colon carcinoma.

    Science.gov (United States)

    Kinori, Michael; Ben Bassat, Iris; Huna-Baron, Ruth

    2011-02-01

    Isolated cranial mononeuropathies in patients over 50 years of age most commonly result from microvascular ischemic demyelination. A 51-year-old female without vasculopathic risk factors presented with isolated sixth nerve palsy. Magnetic resonance imaging (MRI) of the brain and orbits revealed a cavernous sinus lesion that was diagnosed as a meningioma. Laboratory tests showed abnormal liver function, and an abdominal computerized tomogram demonstrated an obstructive colonic mass with liver metastasis. The pathology tests of specimens taken during a laparotomy diagnosed colon adenocarcinoma. The MRI interpretation was changed to cavernous sinus metastasis from a primary adenocarcinoma of the colon. This case had common cranial nerve symptoms but with a very rare etiology, emphasizing the importance of a high index of suspicion of remote origins in patients with isolated sixth nerve palsy and no atherosclerotic risk factors.

  1. BVES regulates EMT in human corneal and colon cancer cells and is silenced via promoter methylation in human colorectal carcinoma.

    Science.gov (United States)

    Williams, Christopher S; Zhang, Baolin; Smith, J Joshua; Jayagopal, Ashwath; Barrett, Caitlyn W; Pino, Christopher; Russ, Patricia; Presley, Sai H; Peng, DunFa; Rosenblatt, Daniel O; Haselton, Frederick R; Yang, Jin-Long; Washington, M Kay; Chen, Xi; Eschrich, Steven; Yeatman, Timothy J; El-Rifai, Wael; Beauchamp, R Daniel; Chang, Min S

    2011-10-01

    The acquisition of a mesenchymal phenotype is a critical step in the metastatic progression of epithelial carcinomas. Adherens junctions (AJs) are required for suppressing this epithelial-mesenchymal transition (EMT) but less is known about the role of tight junctions (TJs) in this process. Here, we investigated the functions of blood vessel epicardial substance (BVES, also known as POPDC1 and POP1), an integral membrane protein that regulates TJ formation. BVES was found to be underexpressed in all stages of human colorectal carcinoma (CRC) and in adenomatous polyps, indicating its suppression occurs early in transformation. Similarly, the majority of CRC cell lines tested exhibited decreased BVES expression and promoter DNA hypermethylation, a modification associated with transcriptional silencing. Treatment with a DNA-demethylating agent restored BVES expression in CRC cell lines, indicating that methylation represses BVES expression. Reexpression of BVES in CRC cell lines promoted an epithelial phenotype, featuring decreased proliferation, migration, invasion, and anchorage-independent growth; impaired growth of an orthotopic xenograft; and blocked metastasis. Conversely, interfering with BVES function by expressing a dominant-negative mutant in human corneal epithelial cells induced mesenchymal features. These biological outcomes were associated with changes in AJ and TJ composition and related signaling. Therefore, BVES prevents EMT, and its epigenetic silencing may be an important step in promoting EMT programs during colon carcinogenesis.

  2. Dome-type carcinoma of the colon; a rare variant of adenocarcinoma resembling a submucosal tumor: a case report

    Directory of Open Access Journals (Sweden)

    Yamada Masayoshi

    2012-03-01

    Full Text Available Abstract Background Dome-type carcinoma (DC is a distinct variant of colorectal adenocarcinoma and less than 10 cases have been described in the literature. Most of the previously reported cases were early lesions and no endoscopic observations have been described so far. We herein report a case of a DC invading the subserosal layer, including endoscopic findings. Case presentation A highly elevated lesion in the transverse colon was diagnosed by colonoscopy in a 77-year-old man. The tumor appeared to be similar to a submucosal tumor (SMT, however, a demarcated area of reddish and irregular mucosa was observed at the top of the tumor. There were no erosions or ulcers. Laparoscopic-assisted right hemicolectomy was performed and pathological examination revealed a well-circumscribed tumor invading the subserosal layer. The tumor was a well-differentiated adenocarcinoma associated with a dense lymphocytic infiltration and showed expansive growth. The overlying mucosal layer showed high-grade dysplasia. Conclusion The present lesion was diagnosed as a DC of the colon invading the subserosal layer. Because the association of mucosal dysplasia is common in DCs, the detection of dysplastic epithelium would be important to discriminate DCs from SMTs.

  3. Successful radioimmunotherapy of established syngeneic rat colon carcinoma with 211At-mAb

    DEFF Research Database (Denmark)

    Eriksson, Sophie E; Bäck, Tom; Elgström, Erika

    2013-01-01

    Most carcinomas are prone to metastasize despite successful treatment of the primary tumor. One way to address this clinical challenge may be targeted therapy with α-emitting radionuclides such as astatine-211 (211At). Radioimmunotherapy utilizing α-particle emitting radionuclides is considered...

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    BACKGROUND: Resection of colon cancer with curative intent implies clear margins. An arbitrary requirement of 2 cm DtLM generally ensures surgical and pathological clearance. However, harvest of tumor-draining lymph nodes is related to DtLM. For this reason, an extended longitudinal margin become...

  5. Microsatellite alteration and immunohistochemical expression profile of chromosome 9p21 in patients with sporadic renal cell carcinoma following surgical resection

    International Nuclear Information System (INIS)

    El-Mokadem, Ismail; Lim, Alison; Kidd, Thomas; Garret, Katherine; Pratt, Norman; Batty, David; Fleming, Stewart; Nabi, Ghulam

    2016-01-01

    Long-term prognostic significance of loss of heterozygosity on chromosome 9p21 for localized renal cell carcinoma following surgery remains unreported. The study assessed the frequency of deletions of different loci of chromosome 9p along with immunohistochemical profile of proteins in surgically resected renal cancer tissue and correlated this with long-term outcomes. DNA was extracted from renal tumours and corresponding normal kidney tissues in prospectively collected samples of 108 patients who underwent surgical resection for clinically localized disease between January 2001 and December 2005, providing a minimum of 9 years follow-up for each participant. After checking quality of DNA, amplified by PCR, loss of heterozygosity (LOH) on chromosome 9p was assessed using 6 microsatellite markers in 77 clear cell carcinoma. Only 5 of the markers showed LOH (D9S1814, D9S916, D9S974, D9S942, and D9S171). Protein expression of p15(INK4b), p16(INK4a), p14(ARF), CAIX, and adipose related protein (ADFP) were demonstrated by immunostaining in normal and cancer tissues. Loss of heterozygosity for microsatellite analysis was correlated with tumour characteristics, recurrence free, cancer specific, and overall survival, including significance of immunohistochemical profile of protein expressions. The main deletion was found at loci telomeric to CDKN2A region at D9S916. There was a significant correlation between frequency of LOH stage (p = 0.005) and metastases (p = 0.006) suggesting a higher LOH for advanced and aggressive renal cell carcinoma. Most commonly observed LOH in the 3 markers: D9S916, D9S974, and D9S942 were associated with poor survival, and were statistically significant on multivariate analysis. Immunohistochemical expression of p14, p15, and p16 proteins were either low or absent in cancer tissue compared to normal. Loss of heterozygosity of p921 chromosome is associated with aggressive tumours, and predicts cancer specific or recurrence free survival on

  6. Introduction to Sporadic Groups

    Directory of Open Access Journals (Sweden)

    Luis J. Boya

    2011-01-01

    Full Text Available This is an introduction to finite simple groups, in particular sporadic groups, intended for physicists. After a short review of group theory, we enumerate the 1+1+16=18 families of finite simple groups, as an introduction to the sporadic groups. These are described next, in three levels of increasing complexity, plus the six isolated ''pariah'' groups. The (old five Mathieu groups make up the first, smallest order level. The seven groups related to the Leech lattice, including the three Conway groups, constitute the second level. The third and highest level contains the Monster group M, plus seven other related groups. Next a brief mention is made of the remaining six pariah groups, thus completing the 5+7+8+6=26 sporadic groups. The review ends up with a brief discussion of a few of physical applications of finite groups in physics, including a couple of recent examples which use sporadic groups.

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

    Directory of Open Access Journals (Sweden)

    Irene Irene

    2011-04-01

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

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

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    Srikanth Umakanthan

    2015-01-01

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

  9. Metabolite profiling of human colon carcinoma – deregulation of TCA cycle and amino acid turnover

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    Noske Aurelia

    2008-09-01

    Full Text Available Abstract Background Apart from genetic alterations, development and progression of colorectal cancer has been linked to influences from nutritional intake, hyperalimentation, and cellular metabolic changes that may be the basis for new diagnostic and therapeutic approaches. However, in contrast to genomics and proteomics, comprehensive metabolomic investigations of alterations in malignant tumors have rarely been conducted. Results In this study we investigated a set of paired samples of normal colon tissue and colorectal cancer tissue with gas-chromatography time-of-flight mass-spectrometry, which resulted in robust detection of a total of 206 metabolites. Metabolic phenotypes of colon cancer and normal tissues were different at a Bonferroni corrected significance level of p = 0.00170 and p = 0.00005 for the first two components of an unsupervised PCA analysis. Subsequent supervised analysis found 82 metabolites to be significantly different at p Conclusion This study demonstrates that metabolic profiling facilitates biochemical phenotyping of normal and neoplastic colon tissue at high significance levels and points to GC-TOF-based metabolomics as a new method for molecular pathology investigations.

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

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    Mingshun Chen

    2016-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Abdul Azeez Ahamed Riyaaz

    2016-01-01

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

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

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    Christian Melle

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

  13. Operative Method for Transverse Colon Carcinoma: Transverse Colectomy Versus Extended Colectomy.

    Science.gov (United States)

    Chong, Choon Seng; Huh, Jung Wook; Oh, Bo Young; Park, Yoon Ah; Cho, Yong Beom; Yun, Seong Hyeon; Kim, Hee Cheol; Lee, Woo Yong

    2016-07-01

    The type of surgery performed for primary transverse colon cancer varies based on tumor characteristics and surgeon perspective. The optimal oncological outcome following different surgical options has not been clearly established, and transverse colectomy has shown oncological equivalence only in small cohort studies. Our aim was to compare long-term oncological outcomes after transverse colectomy versus extended resection for transverse colon cancer. This study is a retrospective review of prospectively collected data. This study was conducted at a tertiary care hospital. All patients treated for transverse colon cancer at the Samsung Medical Center between 1995 and 2013 were included. Oncological outcomes were compared between 2 groups of patients: a transverse colectomy group and an extended colectomy group (which included extended right hemicolectomy and left hemicolectomy). A total of 1066 patients were included, of whom 750 (70.4%) underwent extended right hemicolectomy, 127 (11.9%) underwent transverse colectomy, and 189 (17.7%) underwent left hemicolectomy. According to univariate analysis, surgical approach, histological type, tumor morphology, cancer T and N stage, cancer size, and lymphovascular invasion were significant factors contributing to disease-free survival (DFS). However, as seen in multivariate analysis, only node-positive disease (HR = 2.035 (1.188-3.484)), tumors with ulcerative morphology (HR = 3.643 (1.132-11.725)), and the presence of vascular invasion (HR = 2.569 (1.455-4.538)) were significant factors for DFS. Further analysis with a propensity-matched cohort between the transverse and extended colectomy groups demonstrated no significant differences in DFS and overall survival. This study was limited because it was performed at a single institution and it was retrospective in nature. In terms of perioperative and oncological outcomes, transverse colectomy and extended colectomy did not differ despite a shorter specimen length and

  14. Monoterpene bisindole alkaloids, from the African medicinal plant Tabernaemontana elegans, induce apoptosis in HCT116 human colon carcinoma cells.

    Science.gov (United States)

    Mansoor, Tayyab A; Borralho, Pedro M; Dewanjee, Saikat; Mulhovo, Silva; Rodrigues, Cecília M P; Ferreira, Maria-José U

    2013-09-16

    Tabernaemontana elegans is a medicinal plant used in African traditional medicine to treat several ailments including cancer. The aims of the present study were to identify anti-cancer compounds, namely apoptosis inducers, from Tabernaemontana elegans, and hence to validate its usage in traditional medicine. Six alkaloids, including four monomeric indole (1-3, and 6) and two bisindole (4 and 5) alkaloids, were isolated from the methanolic extract of Tabernaemontana elegans roots. The structures of these compounds were characterized by 1D and 2D NMR spectroscopic and mass spectrometric data. Compounds 1-6 along with compound 7, previously isolated from the leaves of the same species, were evaluated for in vitro cytotoxicity against HCT116 human colon carcinoma cells by the MTS metabolism assay. The cytotoxicity of the most promising compounds was corroborated by Guava-ViaCount flow cytometry assays. Selected compounds were next studied for apoptosis induction activity in HCT116 cells, by evaluation of nuclear morphology following Hoechst staining, and by caspase-3 like activity assays. Among the tested compounds (1-7), the bisindole alkaloids tabernaelegantine C (4) and tabernaelegantinine B (5) were found to be cytotoxic to HCT116 cells at 20 µM, with compound 5 being more cytotoxic than the positive control 5-Fluorouracil (5-FU), at a similar dose. In fact, even at 0.5 µM, compound 5 was more potent than 5-FU. Compounds 4 and 5 induced characteristic patterns of apoptosis in HCT116 cancer cells including, cell shrinkage, condensation, fragmentation of the nucleus, blebbing of the plasma membrane and chromatin condensation. Further, general caspase-3-like activity was increased in cells exposed to compounds 4 and 5, corroborating the nuclear morphology evaluation assays. Bisindole alkaloids tabernaelegantine C (4) and tabernaelegantinine B (5) were characterized as potent apoptosis inducers in HCT116 human colon carcinoma cells and as possible lead/scaffolds for

  15. Differential Expression of Wnt Pathway Genes in Sporadic Hepatocellular Carcinomas Infected With Hepatitis B Virus Identified With OligoGE Arrays.

    Science.gov (United States)

    Lin, Xiaoyan; Wang, Qiangxiu; Cao, Zhixin; Geng, Ming; Cao, Yongcheng; Liu, Xiaohong

    2013-01-01

    Epidemiological evidence has clearly indicated that chronic infection with the hepatitis B virus (HBV) is the major risk factor for developing hepatocellular carcinoma (HCC). Nonetheless, the mechanisms by which HBV contributes to the pathogenesis of HCC have not been fully elucidated. Our aim was to characterize differential gene expression profiles related to the Wnt signaling pathway between primary tumor and adjacent normal tissues in HCC patients with concomitant HBVinfection . An oligoGEArray® (an oligonucleotide-based gene expression array platform) containing 126 Wnt signaling pathway-related genes was used to compare gene expressions between primary HCC and adjacent non-tumorous liver tissues from 10 patients with HCC. Selected differential genes were identified with real-time RT-PCR and immunohistochemistry (IHC). In particular, the protein of the differential gene DVL3 (disheveled, dsh homolog 3 [Drosophila]) was chosen to investigate whether it is up regulated in primary tumor correlated with the clinic pathological characteristics of HCC patients. For this purpose we examined 56 HCC tissue samples via IHC for the presence of DVL3 protein. Sixteen genes were identified with significant differential expression between HCC and adjacent non-tumorous liver tissue. These genes have been previously associated with the Frizzled signaling pathway, cell cycle, transcription, or protein degradation. All (100%) of the tumor samples results from 56 HCC patients tested were positive for DVL3 via IHC. Based on the intensity of DVL3 immunoreactivity, 25 (44.6%) and 31 (55.4%) of the patients were classified aslow and high-DVL3, respectively, which correlated with tumor stage (P = 0.029). This study clarified a number of Wnt pathway-related genes which are dysregulated in HBV-associated HCC. These genes may be contributedto the frequent activation of the Wnt signaling pathway. Our results promote the role of the Wnt signaling pathway in HBV-associated HCC.

  16. Endoscopic tattooing of early colon carcinoma enhances detection of lymph nodes most prone to harbor tumor burden.

    Science.gov (United States)

    Aldecoa, Iban; Montironi, Carla; Planell, Nuria; Pellise, Maria; Fernandez-Esparrach, Gloria; Gines, Angels; Delgado, Salvadora; Momblan, Dulce; Moreira, Leticia; Lopez-Ceron, Maria; Rakislova, Natalia; Martinez-Palli, Graciela; Balust, Jaume; Bombi, Josep Antoni; de Lacy, Antonio; Castells, Antoni; Balaguer, Francesc; Cuatrecasas, Miriam

    2017-02-01

    Colorectal cancer (CRC) screening programs result in the detection of early-stage asymptomatic carcinomas suitable to be surgically cured. Lymph nodes (LN) from early CRC are usually small and may be difficult to collect. Still, at least 12 LNs should be analyzed from colectomies, to ensure a reliable pN0 stage. Presurgical endoscopic tattooing improves LN procurement. In addition, molecular detection of occult LN tumor burden in histologically pN0 CRC patients is associated with a decreased survival rate. We aimed to study the impact of presurgical endoscopic tattooing on the molecular detection of LN tumor burden in early colon neoplasms. A prospective cohort study from a CRC screening-based population was performed at a tertiary academic hospital. LNs from colectomies with and without preoperative endoscopic tattooing were assessed by two methods, hematoxylin and eosin (HE), and RT-LAMP, to detect tumor cytokeratin 19 (CK19) mRNA. We compared the amount of tumor burden and LN yields from tattooed and non-tattooed specimens. HE and RT-LAMP analyses of 936 LNs were performed from 71 colectomies containing early carcinomas and endoscopically unresectable adenomas (8 pT0, 17 pTis, 27 pT1, 19 pT2); 47 out of 71 (66.2 %) were tattooed. Molecular positivity correlated with the presence of tattoo in LN [p < 0.001; OR 3.1 (95 % CI 1.7-5.5)]. A significantly higher number of LNs were obtained in tattooed specimens (median 17 LN vs. 14.5 LN; p = 0.019). Endoscopic tattooing enables the analysis of those LNs most prone to harbor tumor cells and improves the number of LN harvested.

  17. Analysis of APC allelic imbalance/loss of heterozygosity and APC protein expression in cutaneous squamous cell carcinomas.

    LENUS (Irish Health Repository)

    Gray, Sarah E

    2011-05-01

    The adenomatous polyposis coli (APC) gene is a tumor suppressor gene which is mutated in the hereditary disease, familial adenomatous polyposis (FAP). Somatic mutations of the APC gene have also been identified in the majority of sporadic colorectal carcinomas, and mutation of the APC gene appears to be an early step in the initiation of colon cancer. Loss of heterozygosity (LOH) of APC has been described in a variety of other cancer types, including renal cell carcinoma, gastric cancer, non-small cell lung cancer, endometrial cancer and oral squamous cell carcinomas (SCC).

  18. Clinical Significance of Microsatellite Instability in Sporadic Epithelial Ovarian Tumors

    OpenAIRE

    Yoon, Bo-Sung; Kim, Young-Tae; Kim, Jae-Hoon; Kim, Sang-Wun; Nam, Eun-Ji; Cho, Nam-Hoon; Kim, Jae-Wook; Kim, Sunghoon

    2008-01-01

    Purpose We evaluated the expression of microsatellite instability (MSI) in sporadic ovarian tumors using 5 standard and 9 new MSI markers to determine the clinical significance of MSI in sporadic epithelial ovarian tumors. Materials and Methods MSI was examined in 21 borderline and 25 malignant ovarian tumors. Polymerase chain reaction (PCR) was performed using the 5 markers recommended by the National Cancer Institute (NCI) for colon cancer and 9 additional markers. MSI was determined using ...

  19. Loss of tumorigenicity of murine colon carcinoma MC38/0 cell line after transduction with a retroviral vector carrying murine IL-12 genes

    Czech Academy of Sciences Publication Activity Database

    Pajtasz-Piasecka, E.; Szyda, A.; Rossowska, J.; Krawczenko, A.; Indrová, Marie; Grabarczyk, P.; Wysocki, P.; Mackiewicz, A.; DuĽ, D.

    2004-01-01

    Roč. 50, č. 1 (2004), s. 7-14 ISSN 0015-5500 Grant - others:State Committee for Scientific Research of the Republic of Poland (KBN)(PL) PBZ-KBN 004/PO4/98/5f Institutional research plan: CEZ:AV0Z5052915 Keywords : MC38 murine colon carcinoma * IL-12 transduction * tumorigenicity Subject RIV: EC - Immunology Impact factor: 0.507, year: 2004

  20. Differential effector mechanisms induced by vaccination with MUC1 DNA in the rejection of colon carcinoma growth at orthotopic sites and metastases.

    Science.gov (United States)

    Sugiura, Daisuke; Aida, Satoshi; Denda-Nagai, Kaori; Takeda, Kazuyoshi; Kamata-Sakurai, Mika; Yagita, Hideo; Irimura, Tatsuro

    2008-12-01

    The effects of MUC1 DNA vaccination on the orthotopic growth and liver metastasis of colon carcinoma cells were investigated in mice. Vaccination with MUC1 DNA resulted in immune responses that were effective in suppressing mouse colon carcinoma cells transfected with MUC1 cDNA. CD4+ T cells but not CD8+ T cells mediated this antitumor response as shown by the in vivo depletion of lymphocyte subpopulations with the use of anti-CD4 or anti-CD8 antibody. The effects of neutralizing antibodies in vivo revealed that the predominant effector molecule in preventing orthotopic tumor growth was FasL, whereas the effector molecule effective in preventing liver metastasis was tumor necrosis factor-alpha. Colon carcinoma cells isolated from tumors growing in the ceca, spleens, and livers were shown to be equally sensitive to FasL and tumor necrosis factor-alpha. The results strongly suggest that elimination of tumor cells initiated by DNA vaccination in the present protocol is mediated by antigen-specific CD4+ T cells and the effector mechanisms in the cecum and in the liver are distinct due to a unique organ microenvironment.

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

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    Sara Bar-Yehuda

    2005-01-01

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

  2. Younger Age Is Associated with Poorer Survival in Patients with Signet-Ring Cell Carcinoma of the Colon without Distant Metastasis

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    Ben Huang

    2016-01-01

    Full Text Available Background. In general, younger age is associated with better survival in patients with colon cancer. In this study, we aim to analyze the impact of age on cancer-specific survival (CSS in patients with signet-ring cell carcinoma (SRCC of the colon, a particularly aggressive type of colon cancer. Methods. Information on patients with SRCC of the colon with no distant metastasis was extracted from the US Surveillance, Epidemiology, and End Results (SEER database. An X-tile plot was used to determine the optimal cutoff age at diagnosis. Results. A total of 776 patients were included in data analysis. The X-tile program revealed an optimal cutoff at 35 years of age. A higher percentage of stage III disease and a higher percentage of N2 disease were observed in patients ≤ 35 years of age. The multivariate Cox proportional model demonstrated that patients ≤ 35 years of age were more likely to have a poorer survival outcome compared with patients aged >35 years (HR 1.411, 95% CI 1.032–1.929, and P=0.031. Conclusion. In contrast to the association of younger age with better survival in colon cancer patients, younger age (≤35 years is associated with poorer survival outcome in patients with SRCC of the colon without distant metastasis.

  3. Laparoscopic colectomy for transverse colon carcinoma: a surgical challenge but oncologically feasible.

    Science.gov (United States)

    Fernández-Cebrián, J M; Gil Yonte, P; Jimenez-Toscano, M; Vega, L; Ochando, F

    2013-02-01

    The aim of the study was to assess the safety and feasibility of laparoscopic surgery for transverse colon cancer and to compare the clinicopathological outcome with that of conventional open surgery. From March 1998 to December 2009, 1253 patients with colorectal tumours were operated on, 564 laparoscopically. There were 154 cases of transverse colon cancer, 86 of which were included in the study. Details were collected on age, sex, body mass index (BMI), operation time, blood loss, time to first flatus, time to resume a liquid diet, postoperative length of hospital stay, complications, TNM stage, tumour size, distal resection margin, proximal resection margin, number of nodes harvested and surgical procedure. Laparoscopic and open surgical removal was compared. No significant differences were found between laparoscopic and conventional groups in age, sex, BMI, operation time or postoperative length of hospital stay. The mean blood loss during the operations was significantly less in the laparoscopic group (105.9 ± 140.9 ml vs 305.7 ± 325.3 ml; P = 0.05). The time to the first flatus was shorter (2.1 ± 0.3 days vs 3.8 ± 3.0 days; P = 0.043) and diet was started earlier (3.1 ± 1.4 days vs 3.4 ± 1.5 days) in the laparoscopic group. No significant differences in tumour size, proximal resection margin or number of lymph nodes were observed. The mean distal resection margin was not statistically different (10.3 ± 4.5 cm vs 8.8 ± 4.9 cm). At a mean follow up of 33 ± 2.3 months, nonport-site metastases occurred in eight patients and locoregional recurrence occurred in three, with no significant difference between the groups. The 3-year cumulative overall survival rate was 78%, and the disease-free survival rate was 69%. There was no difference in the outcome of laparoscopic and open surgery for transverse colon cancer, including the cancer-specific outcome. © 2012 The Authors Colorectal Disease © 2012 The Association of

  4. Dietary compounds that induce cancer preventive phase 2 enzymes activate apoptosis at comparable doses in HT29 colon carcinoma cells.

    Science.gov (United States)

    Kirlin, W G; Cai, J; DeLong, M J; Patten, E J; Jones, D P

    1999-10-01

    Dietary agents that induce glutathione S-transferases and related detoxification systems (Phase 2 enzyme inducers) are thought to prevent cancer by enhancing elimination of chemical carcinogens. The present study shows that compounds of this group (benzyl isothiocyanate, allyl sulfide, dimethyl fumarate, butylated hydroxyanisole) activated apoptosis in human colon carcinoma (HT29) cells in culture over the same concentration ranges that elicited increases in enzyme activity (5-25, 25-100, 10-100, 15-60 micromol/L, respectively). Pretreatment of cells with sodium butyrate, an agent that induces HT29 cell differentiation, resulted in parallel increases in Phase 2 enzyme activities and induction of apoptosis in response to the inducers. Cell death characteristics included apoptotic morphological changes, appearance of cells at sub-G1 phase on flow cytometry, caspase activation, DNA fragmentation and TUNEL-positive staining. The results suggest that dietary Phase 2 inducers may protect against cancer by a mechanism distinct from and in addition to that associated with enhanced elimination of carcinogens. If this occurs in vivo, diets high in such compounds could eliminate precancerous cells by apoptosis at time points well after initial exposure to chemical mutagens and carcinogens.

  5. F-18 Labeled Vasoactive Intestinal Peptide Analogue in the PET Imaging of Colon Carcinoma in Nude Mice

    Directory of Open Access Journals (Sweden)

    Dengfeng Cheng

    2013-01-01

    Full Text Available As large amount of vasoactive intestinal peptide (VIP receptors are expressed in various tumors and VIP-related diseases, radiolabeled VIP provides a potential PET imaging agent for VIP receptor. However, structural modification of VIP is required before being radiolabeled and used for VIP receptor imaging due to its poor in vivo stability. As a VIP analogue, [R8, 15, 21, L17]-VIP exhibited improved stability and receptor specificity in preliminary studies. In this study, F-18 labeled [R8,15,21, L17]-VIP was produced with the radiochemical yield being as high as 33.6%±3% (decay-for-corrected, n=5 achieved within 100 min, a specific activity of 255 GBq/μmol, and a radiochemical purity as high as 99% as characterized by radioactive HPLC, TLC, and SDS-Page radioautography. A biodistribution study in normal mice also demonstrated fast elimination of F-18 labeled [R8,15,21, L17]-VIP in the blood, liver, and gastrointestinal tracts. A further micro-PET imaging study in C26 colon carcinoma bearing mice confirmed the high tumor specificity, with the tumor/muscle radioactivity uptake ratio being as high as 3.03 at 60 min following injection, and no apparent radioactivity concentration in the intestinal tracts. In addition, blocking experiment and Western Blot test further confirmed its potential in PET imaging of VIP receptor-positive tumor.

  6. Autonomous inhibition of apoptosis correlates with responsiveness of colon carcinoma cell lines to ciglitazone.

    Directory of Open Access Journals (Sweden)

    David M Baron

    Full Text Available Colorectal cancer is a leading cause of mortality worldwide. Resistance to therapy is common and often results in patients succumbing to the disease. The mechanisms of resistance are poorly understood. Cells basically have two possibilities to survive a treatment with potentially apoptosis-inducing substances. They can make use of their existing proteins to counteract the induced reactions or quickly upregulate protective factors to evade the apoptotic signal. To identify protein patterns involved in resistance to apoptosis, we studied two colorectal adenocarcinoma cell lines with different growth responses to low-molar concentrations of the thiazolidinedione Ciglitazone: HT29 cells underwent apoptosis, whereas SW480 cells increased cell number. Fluorescence detection and autoradiography scans of 2D-PAGE gels were performed in both cell lines to assess protein synthesis and turnover, respectively. To verify the data we performed shotgun analysis using the same treatment procedure as in 2D-experiments. Biological functions of the identified proteins were mainly associated with apoptosis regulation, chaperoning, intrinsic inflammation, and DNA repair. The present study suggests that different growth response of two colorectal carcinoma cell lines after treatment with Ciglitazone results from cell-specific protein synthesis and differences in protein regulation.

  7. Combination hyperthermia and intraarterial 5-FU for metastatic colon carcinoma to liver

    International Nuclear Information System (INIS)

    Moseley, H.S.; Palmquist, M.

    1984-01-01

    Metastatic colorectal carcinoma to the liver remains a formidable challenge. Responses to chemotherapy are brief and the number of effective drugs is very limited. A phase II trial of hepatic hyperthermia and intraarterial chemotherapy was undertaken to attempt to improve response rates and duration. Patients were given a 10 day course of IA 5-FU at 15 mg/kg. During the infusion hyperthermia was given five times using the BSD Annular Phased Array (APA). Thermistors were placed percutaneously into normal liver and tumor using ultrasound or CT scan guidance. Six patients have been treated. Significant problems in positioning ill patients in the APA were encountered, and there was difficulty also in preventing heating throughout the abdominal cavity. Four patients, all with poor performance status, failed to benefit. One patient had improvement in liver function studies for two months and failed to respond on a repeat course. One patient had a complete response which is continuing over 18 months with a liver scan reverting to normal and CEA returning to normal. These preliminary results are promising and warrant further trials

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

    Science.gov (United States)

    Chen, Zhung-Yuan; Hsieh, You-Miin; Huang, Chun-Chih; Tsai, Cheng-Chih

    2017-01-10

    This study was conducted to investigate the inhibitory effect of Lactobacillus cells and supernatants on the growth of the human colon cancer cell line HT-29. Our study results indicated that the PM153 strain exhibits the best adhesion ability and the highest survival in the gastrointestinal tract simulation experiment. Furthermore, after an 8-h co-culture of PM153 and HT-29 cells, the PM153 strain can induce the secretion of nitric oxide from the HT-29 cells. In addition, after the co-culture of the BCRC17010 strain (10⁸ cfu/mL) and HT-29 cells, the Bax/Bcl-2 ratio in the HT-29 cells was 1.19, which showed a significant difference from the other control and LAB groups ( p strain exerts a pro-apoptotic effect on the HT-29 cells. Upon co-culture with HT-29 cells for 4, 8 and 12 h, the BCRC14625 strain (10⁸ cfu/mL) demonstrated a significant increase in lactate dehydrogenase (LDH) activity ( p strains have ability to inhibit the growth of the colorectal cancer cell line HT-29 Bax/Bcl-2 pathway or NO production. In summary, we demonstrated that the BCRC17010 strain, good abilities of adhesion and increased LDH release, was the best probiotic potential for inhibition of HT-29 growth amongst the seven LAB strains tested in vitro.

  9. The role of tumor markers (CEA, TPA, CA 19-9) in colon and rectum carcinomas

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    Cangemi, V.; Volpino, P.; Fiori, E.; Giammarco, A.; Piat, G.

    1987-01-01

    We have evaluated the diagnostic efficacy (sensitivity, specificity, accuracy, predictive malignancy index) of CEA, TPA, CA 19-9 in colon and rectum tumors (56 cases), the difference in behaviour of these markers in relation to the stage and grading of the cancer, their reliability regarding postsurgical relapses and/or metastases. The sensitivity of CEA (>10 ng/ml), TPA (>130 U/L), CA 19-9 (>37 u/ml) for diagnostic purpose was rather limited (28.6% - 30% - 18.5%) with a malignancy prediction value of 100% - 81.8% - 62.5%. With regard to relapses and/or metastases, the diagnostic efficacy of the marker proved to be evident only for CEA, TPA, CA 19-9 value greater than 25 ng/ml, 250 U/L and 100 u/ml. The use of thethree markers together was certainly an advantage both for primitive tumors (sensitivity: 52.8%) and relapses and/or metastases after surgery (sensitivity: 66.7%)

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

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    Greulich Karl

    2010-10-01

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

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

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    Hamid Deva Shaiq

    2013-01-01

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

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

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

    2017-12-01

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

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

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    Zhung-Yuan Chen

    2017-01-01

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

  14. Colorectal carcinomas with microsatellite instability display a different pattern of target gene mutations according to large bowel site of origin

    International Nuclear Information System (INIS)

    Pinheiro, Manuela; Fragoso, Maria; Santos, Lúcio; Henrique, Rui; Lopes, Paula; Lopes, Carlos; Lothe, Ragnhild A; Teixeira, Manuel R; Ahlquist, Terje; Danielsen, Stine A; Lind, Guro E; Veiga, Isabel; Pinto, Carla; Costa, Vera; Afonso, Luís; Sousa, Olga

    2010-01-01

    Only a few studies have addressed the molecular pathways specifically involved in carcinogenesis of the distal colon and rectum. We aimed to identify potential differences among genetic alterations in distal colon and rectal carcinomas as compared to cancers arising elsewhere in the large bowel. Constitutional and tumor DNA from a test series of 37 patients with rectal and 25 patients with sigmoid carcinomas, previously analyzed for microsatellite instability (MSI), was studied for BAX, IGF2R, TGFBR2, MSH3, and MSH6 microsatellite sequence alterations, BRAF and KRAS mutations, and MLH1 promoter methylation. The findings were then compared with those of an independent validation series consisting of 36 MSI-H carcinomas with origin from each of the large bowel regions. Immunohistochemical and germline mutation analyses of the mismatch repair system were performed when appropriate. In the test series, IGFR2 and BAX mutations were present in one and two out of the six distal MSI-H carcinomas, respectively, and no mutations were detected in TGFBR2, MSH3, and MSH6. We confirmed these findings in the validation series, with TGFBR2 and MSH3 microsatellite mutations occurring less frequently in MSI-H rectal and sigmoid carcinomas than in MSI-H colon carcinomas elsewhere (P = 0.00005 and P = 0.0000005, respectively, when considering all MSI-carcinomas of both series). No MLH1 promoter methylation was observed in the MSI-H rectal and sigmoid carcinomas of both series, as compared to 53% found in MSI-H carcinomas from other locations (P = 0.004). KRAS and BRAF mutational frequencies were 19% and 43% in proximal carcinomas and 25% and 17% in rectal/sigmoid carcinomas, respectively. The mechanism and the pattern of genetic changes driving MSI-H carcinogenesis in distal colon and rectum appears to differ from that occurring elsewhere in the colon and further investigation is warranted both in patients with sporadic or hereditary disease

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

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    Yahia Z Gad

    2011-03-01

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

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

    Science.gov (United States)

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

    2001-01-01

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

  17. Inhibition of the liver enriched protein FOXA2 recovers HNF6 activity in human colon carcinoma and liver hepatoma cells.

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    Frank Lehner

    Full Text Available Recently, we demonstrated that the transcription factors HNF6 and FOXA2 function as key regulators in human colorectal liver metastases. To better understand their proposed inhibitory crosstalk, the consequences of functional knockdown of FOXA2 on HNF6 and C/EBPα activity were investigated in the human colon Caco-2 and HepG2 carcinoma cell lines. Specifically, siRNA-mediated gene silencing of FOXA2 repressed transcript expression by >80%. This resulted in a statistically significant 6-, 3-, 4-, and 8-fold increase in mRNA expression of HNF6 and of genes targeted by this transcription factor, e.g., HSP105B, CYP51, and C/EBPα, as determined by qRT-PCR. Thus, functional knockdown of FOXA2 recovered HNF6 activity. Furthermore, with nuclear extracts of Caco-2 cells no HNF6 DNA binding was observed, but expression of HNF1α, FOXA2, FOXA3, and HNF4α protein was abundant. We therefore transfected a plasmid encoding HNF6 into Caco-2 cells but also employed a retroviral vector to transfect HNF6 into HepG2 cells. This resulted in HNF6 protein expression with DNA binding activity being recovered as determined by EMSA band shift assays. Furthermore, by flow cytometry the consequences of HNF6 expression on cell cycle regulation in transfected cells was studied. Essentially, HNF6 inhibited cell cycle progression in the G2/M and G1 phase in Caco-2 and HepG2 cell lines, respectively. Here, proliferation was reduced by 80% and 50% in Caco-2 and HepG2 cells, respectively, as determined by the BrdU labeling assay. Therefore functional knockdown of FOXA2 recovered HNF6 activity and inhibited growth of tumor-cells and may possibly represent a novel therapeutic target in primary and secondary liver malignancies.

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

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    EMANUELA FELLEY-BOSCO

    2002-01-01

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

  19. Integrin α3β1 can function to promote spontaneous metastasis and lung colonization of invasive breast carcinoma.

    Science.gov (United States)

    Zhou, Bo; Gibson-Corley, Katherine N; Herndon, Mary E; Sun, Yihan; Gustafson-Wagner, Elisabeth; Teoh-Fitzgerald, Melissa; Domann, Frederick E; Henry, Michael D; Stipp, Christopher S

    2014-01-01

    Significant evidence implicates α3β1 integrin in promoting breast cancer tumorigenesis and metastasis-associated cell behaviors in vitro and in vivo. However, the extent to which α3β1 is actually required for breast cancer metastasis remains to be determined. We used RNA interference to silence α3 integrin expression by approximately 70% in 4T1 murine mammary carcinoma cells, a model of aggressive, metastatic breast cancer. Loss of α3 integrin reduced adhesion, spreading, and proliferation on laminin isoforms, and modestly reduced the growth of orthotopically implanted cells. However, spontaneous metastasis to lung was strikingly curtailed. Experimental lung colonization after tail vein injection revealed a similar loss of metastatic capacity for the α3-silenced (α3si) cells, suggesting that critical, α3-dependent events at the metastatic site could account for much of α3β1's contribution to metastasis in this model. Reexpressing α3 in the α3si cells reversed the loss of metastatic capacity, and silencing another target, the small GTPase RhoC, had no effect, supporting the specificity of the effect of silencing α3. Parental, α3si, and α3-rescued cells, all secreted abundant laminin α5 (LAMA5), an α3β1 integrin ligand, suggesting that loss of α3 integrin might disrupt an autocrine loop that could function to sustain metastatic growth. Analysis of human breast cancer cases revealed reduced survival in cases where α3 integrin and LAMA5 are both overexpressed. α3 integrin or downstream effectors may be potential therapeutic targets in disseminated breast cancers, especially when laminin α5 or other α3 integrin ligands are also over-expressed. ©2013 AACR.

  20. Bacteriophages support anti-tumor response initiated by DC-based vaccine against murine transplantable colon carcinoma.

    Science.gov (United States)

    Pajtasz-Piasecka, Elzbieta; Rossowska, Joanna; Duś, Danuta; Weber-Dabrowska, Beata; Zabłocka, Agnieszka; Górski, Andrzej

    2008-02-15

    Bacteriophages in eukaryotic hosts may behave as particulate antigens able to activate the innate immune system and generate adaptive immunity. Dendritic cells (DCs) play a key role in the initiation of the immune response, mainly by priming T cell-mediated immunity. For this reason, they are increasingly applied as an adjuvant for effective anti-tumor therapies in animal models as well as in a few clinical trials. The presented study focused on the application of mouse DCs which were activated with T4 bacteriophages (T4 phages, T4) and further loaded with tumor antigens (TAg) in inducing an anti-tumor response. The activation of bone marrow-derived DCs with T4 phages and TAg resulted in augmentation of their differentiation marker expression accompanied by an enhanced ability to prime T cells for IFN-gamma production. These activated DCs (BM-DC/T4+TAg) were used in experimental immunotherapy of C57BL/6 mice bearing advanced MC38 colon carcinoma tumors. As a result of their triple application, a significant tumor growth delay, up to 19 days, was observed compared with the controls - treated with BM-DCs activated only with T4 phages, TAg, or lipopolysaccharide solution ["solvent"], where the tumor growth delay did not exceed 7 days. The percentage of tumor growth inhibition estimated 10 days after the third cell injection ranged from 32% (for animals treated with BM-DC/TAg cells) to 76% (for animals treated with BM-DC/T4+TAg cells) over the tumor-bearing untreated control mice. The obtained data indicate that in vitro interactions between T4 phages and BM-DCs followed by TAg activation caused augmentation of the anti-tumor effect when DCs were used as a vaccine for tumor-bearing mice treatment. Therefore, pretreatment of DCs with the phages may be considered as a beneficial element of a novel strategy in anti-tumor immunotherapy.

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

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    Satolli Maria A

    2006-11-01

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

  2. PDGF suppresses the sulfation of CD44v and potentiates CD44v-mediated binding of colon carcinoma cells to fibrin under flow.

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    Christina S Alves

    Full Text Available Fibrin(ogen mediates sustained tumor cell adhesion and survival in the pulmonary vasculature, thereby facilitating the metastatic dissemination of tumor cells. CD44 is the major functional fibrin receptor on colon carcinoma cells. Growth factors, such as platelet-derived growth factor (PDGF, induce post-translational protein modifications, which modulate ligand binding activity. In view of the roles of PDGF, fibrin(ogen and CD44 in cancer metastasis, we aimed to delineate the effect of PDGF on CD44-fibrin recognition. By immunoprecipitating CD44 from PDGF-treated and untreated LS174T colon carcinoma cells, which express primarily CD44v, we demonstrate that PDGF enhances the adhesion of CD44v-coated beads to immobilized fibrin. Enzymatic inhibition studies coupled with flow-based adhesion assays and autoradiography reveal that PDGF augments the binding of CD44v to fibrin by significantly attenuating the extent of CD44 sulfation primarily on chondroitin and dermatan sulfate chains. Surface plasmon resonance assays confirm that PDGF enhances the affinity of CD44v-fibrin binding by markedly reducing its dissociation rate while modestly increasing the association rate. PDGF mildly reduces the affinity of CD44v-hyaluronan binding without affecting selectin-CD44v recognition. The latter is attributed to the fact that CD44v binds to selectins via sialofucosylated O-linked residues independent of heparan, dermatan and chondroitin sulfates. Interestingly, PDGF moderately reduces the sulfation of CD44s and CD44s-fibrin recognition. Collectively, these data offer a novel perspective into the mechanism by which PGDF regulates CD44-dependent binding of metastatic colon carcinoma cells to fibrin(ogen.

  3. Monitoring Cell Death in Regorafenib-Treated Experimental Colon Carcinomas Using Annexin-Based Optical Fluorescence Imaging Validated by Perfusion MRI.

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    Philipp M Kazmierczak

    Full Text Available To investigate annexin-based optical fluorescence imaging (OI for monitoring regorafenib-induced early cell death in experimental colon carcinomas in rats, validated by perfusion MRI and multiparametric immunohistochemistry.Subcutaneous human colon carcinomas (HT-29 in athymic rats (n = 16 were imaged before and after a one-week therapy with regorafenib (n = 8 or placebo (n = 8 using annexin-based OI and perfusion MRI at 3 Tesla. Optical signal-to-noise ratio (SNR and MRI tumor perfusion parameters (plasma flow PF, mL/100mL/min; plasma volume PV, % were assessed. On day 7, tumors underwent immunohistochemical analysis for tumor cell apoptosis (TUNEL, proliferation (Ki-67, and microvascular density (CD31.Apoptosis-targeted OI demonstrated a tumor-specific probe accumulation with a significant increase of tumor SNR under therapy (mean Δ +7.78±2.95, control: -0.80±2.48, p = 0.021. MRI detected a significant reduction of tumor perfusion in the therapy group (mean ΔPF -8.17±2.32 mL/100 mL/min, control -0.11±3.36 mL/100 mL/min, p = 0.036. Immunohistochemistry showed significantly more apoptosis (TUNEL; 11392±1486 vs. 2921±334, p = 0.001, significantly less proliferation (Ki-67; 1754±184 vs. 2883±323, p = 0.012, and significantly lower microvascular density (CD31; 107±10 vs. 182±22, p = 0.006 in the therapy group.Annexin-based OI allowed for the non-invasive monitoring of regorafenib-induced early cell death in experimental colon carcinomas, validated by perfusion MRI and multiparametric immunohistochemistry.

  4. Transduction and oncolytic profile of a potent replication-competent adenovirus 11p vector (RCAd11pGFP in colon carcinoma cells.

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    Jim Silver

    Full Text Available Replication-competent adenovirus type 5 (Ad5 vectors promise to be more efficient gene delivery vehicles than their replication-deficient counterparts, and chimeric Ad5 vectors that are capable of targeting CD46 are more effective than Ad5 vectors with native fibers. Although several strategies have been used to improve gene transduction and oncolysis, either by modifying their tropism or enhancing their replication capacity, some tumor cells are still relatively refractory to infection by chimeric Ad5. The oncolytic effects of the vectors are apparent in certain tumors but not in others. Here, we report the biological and oncolytic profiles of a replication-competent adenovirus 11p vector (RCAd11pGFP in colon carcinoma cells. CD46 was abundantly expressed in all cells studied; however, the transduction efficiency of RCAd11pGFP varied. RCAd11pGFP efficiently transduced HT-29, HCT-8, and LS174T cells, but it transduced T84 cells, derived from a colon cancer metastasis in the lung, less efficiently. Interestingly, RCAd11p replicated more rapidly in the T84 cells than in HCT-8 and LS174T cells and as rapidly as in HT-29 cells. Cell toxicity and proliferation assays indicated that RCAd11pGFP had the highest cell-killing activities in HT29 and T84 cells, the latter of which also expressed the highest levels of glycoproteins of the carcinoma embryonic antigen (CEA family. In vivo experiments showed significant growth inhibition of T84 and HT-29 tumors in xenograft mice treated with either RCAd11pGFP or Ad11pwt compared to untreated controls. Thus, RCAd11pGFP has a potent cytotoxic effect on colon carcinoma cells.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Angeliki Tiptiri-Kourpeti

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

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

    Science.gov (United States)

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

    2016-01-01

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

  8. [Acute colonic pseudo-obstruction (Ogilvie syndrome) after nephrectomy for renal carcinoma: persistence after decompressive colonoscopy and spontaneous remission].

    Science.gov (United States)

    Fariña, L A; Iglesias, J M; Villanueva, C; Salvador, J; Laguna, M P; Villavicencio, H

    1993-02-01

    A 65-year-old male patient presented acute dilatation in the ascendant colon on the third post-operative day following nephrectomy due to renal adenocarcinoma. No changes in colonic diameter were seen after decompressive colonoscopy and, while the patient was asymptomatic, conservative therapy was instituted and the picture was resolved in just a few days. The case is used to review the issue of acute colonic pseudo-obstruction and its relationship to urological operations.

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

    Science.gov (United States)

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

    2001-07-01

    We present a case of synchronous breast and colon carcinoma in a pleural effusion, to our knowledge the first such reported case in the English-language literature. The patient was a 55-yr-old white female with known metastatic breast and colon carcinoma who developed a malignant pleural effusion which demonstrated two strikingly different populations of malignant cells by immunohistochemical study of cell block material. One cell population demonstrated a cytokeratin (CK)7+/CK20-/ER+ phenotype, while the other demonstrated a CK7-/CK20+/ER- phenotype, consistent with breast and colon origin, respectively. An immunohistochemical survey of archival breast and colon primary and metastatic carcinomas confirmed the established CK7+/CK20- phenotype of breast and CK7-/CK20+ phenotype of colon primary carcinomas, and the maintenance of this phenotype in metastases thereof. A survey of benign and malignant mesothelial lesions confirmed the absence of staining for estrogen receptor, but showed 6/10 cases weakly positive for CK20, which has not been described in other published series. This unusual case graphically illustrates the utility of cytokeratin subset immunohistochemistry in effusion cytology. Copyright 2001 Wiley-Liss, Inc.

  10. [Senescence-inducing effects of Chinese herbal medicine Tenglong Buzhong Decoction on human colon carcinoma LS-174-T cells and the mechanism].

    Science.gov (United States)

    Hu, Bing; An, Hong-mei; Shen, Ke-ping; Du, Qin

    2010-11-01

    Cell senescence is an important anti-cancer mechanism and may contribute to cancer therapeutic outcome. The present study observed the effects of Tenglong Buzhong Decoction (TLBZD), a Chinese herbal formula, on senescence in human colon carcinoma LS-174-T cells. LS-174-T cells were treated with TLBZD, and morphology change was observed under a microscope. Cell senescence was identified by senescence-associated β-galactosidase (SA-β-gal) staining, and cell cycle was analyzed by flow cytometry. Expressions of p53, p21(WAF1/CIP1), p16 and RB and RB phosphorylation were detected by Western blot. After being treated with TLBZD, LS-174-T cells became enlarged and flattened by morphology; SA-β-gal staining was positive and cell cycle was arrested in G₀/G₁. In addition, up-regulations of p21(WAF1/CIP1) and p16, as well as inhibition of RB phosphorylation were detected in response to TLBZD treatment. Expressions of p53 and RB were unchanged after TLBZD treatment. TLBZD is effective in inducing cell senescence in human colon carcinoma LS-174-T cells, which may relate to up-regulations of p21(WAF1/CIP1) and p16 and inhibition of RB phosphorylation.

  11. Aqueous extract of Curcuma aromatica induces apoptosis and G2/M arrest in human colon carcinoma LS-174-T cells independent of p53.

    Science.gov (United States)

    Hu, Bing; Shen, Ke-Ping; An, Hong-Mei; Wu, Yang; Du, Qin

    2011-02-01

    Curcuma aromatica is a common Chinese herb for treating diseases with blood stasis and has been regarded as an anticancer herb in modern clinical practice. However, the anticancer effects and related molecular mechanisms of Curcuma aromatica remain unclear. In the present study, human colon carcinoma LS-174-T cell line with wild-type p53 was used as a model cell to evaluate the anticancer effects of aqueous extract of Curcuma aromatica (AECA). AECA inhibits LS-174-T cell proliferation in a dose- and time-dependent manner and colony formation in a dose-dependent manner. AECA treatment induces apoptosis accompanied by caspase-8, -9, and -3 activation in LS-174-T cells. Moreover, blocking the activities of these caspases with a specific inhibitor significantly protected LS-174-T cells from AECA-induced apoptosis. AECA treatment also induces G2/M phase arrest in LS-174-T cells. Expression of p53 was unchanged after AECA treatment; specific silence of p53 did not influence AECA-induced apoptosis and G2/M phase arrest. Further, the expression of cyclin B1 and CDK1 was reduced by AECA. This study suggests that AECA might be effective as an antiproliferative herb for colon carcinoma, the antitumor activity of AECA may involve both extrinsic and intrinsic apoptosis, and AECA induces G2/M phase arrest via downregulation of cyclin B1 and CDK1 and without the participation of p53.

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

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

    NARCIS (Netherlands)

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

    1999-01-01

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

  14. Prognostic impact of FoxP3+ regulatory T cells in relation to CD8+ T lymphocyte density in human colon carcinomas.

    Directory of Open Access Journals (Sweden)

    Harry H Yoon

    Full Text Available T-lymphocyte infiltration into colon carcinomas can influence clinical outcome, and interactions among T cell subsets may be more informative than either subset alone. Our objective was to examine the prognostic impact of tumor-infiltrating FoxP3(+ regulatory T cells (Tregs in relation to cytotoxic CD8(+ T lymphocytes in patients with colon carcinomas characterized by DNA mismatch repair (MMR status who participated in adjuvant chemotherapy trials.FoxP3(+ and CD8(+ densities in tumor epithelial and stromal compartments were analyzed by immunohistochemistry and quantified in resected, stage II and III colonic carcinomas (N = 216. Immune marker density was dichotomized at the median and categorized as high vs low. MMR status was classified as MMR deficient (dMMR or proficient (pMMR. Cox models were adjusted for age, stage, and tumor grade.The density of FoxP3+ infiltration was similar in tumor stroma and epithelia, whereas CD8+ was higher in stroma. The prognostic impact of FoxP3+ and CD8+ T cell infiltration was stronger in stroma vs epithelia, and the density of each marker in stroma was independently associated with improved overall survival (OS. However, the impact of FoxP3+ on survival was dependent upon CD8+ density (P interaction = 040. Among CD8+(low tumors, FoxP3+(high cases had significantly improved OS compared to FoxP3+(low cases after adjustment for covariates (hazard ratio 0.43; 95% confidence interval 0.19 to 0.95; P = .030. In contrast, FoxP3+ was not prognostic among CD8+(high tumors. FoxP3+ remained prognostic in CD8+(low tumors after further adjustment for MMR or BRAF(V600E mutation status. Additionally, these immune markers identified a pMMR subgroup with a similarly favorable OS as for dMMR tumors.The prognostic impact of FoxP3+ and CD8+ T cell density are inter-dependent, whereby FoxP3+ exerts a favorable influence on survival only in colon cancers with low CD8+ infiltration.

  15. Acquired resistance to HSP90 inhibitor 17-AAG and increased metastatic potential are associated with MUC1 expression in colon carcinoma cells.

    Science.gov (United States)

    Liu, Xin; Ban, Li-Li; Luo, Gang; Li, Zhi-Yao; Li, Yun-Feng; Zhou, Yong-Chun; Wang, Xi-Cai; Jin, Cong-Guo; Ye, Jia-Gui; Ma, Ding-Ding; Xie, Qing; Huang, You-Guang

    2016-06-01

    Heat shock protein 90 (HSP90) is a molecular chaperone required for the stability and function of many proteins. The chaperoning of oncoproteins by HSP90 enhances the survival, growth, and invasive potential of cancer cells. HSP90 inhibitors are promising new anticancer agents, in which the benzoquinone ansamycin 17-allylamino-17-demethoxygeldanamycin (17-AAG) is currently in clinical evaluation. However, the implications of acquired resistance to this class of drug remain largely unexplored. In the present study, we have generated isogenic human colon cancer cell lines that are resistant to 17-AAG by continued culturing in the compound. Cross-resistance was found with another HSP90 inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin. The resistant cells showed obvious morphology changes with a metastatic phenotype and significant increases in migration and adhesion to collagens. Western blotting analysis of epithelial-mesenchymal transition molecular markers found that expression of E-cadherin downregulated, whereas expression of N-cadherin and β-catenin upregulated in the resistant cells. Mucin 1 (MUC1) has been reported to mediate metastasis as well as chemical resistance in many cancers. Here, we found that MUC1 expression was significantly elevated in the acquired drug resistance cells. 17-AAG treatment could decrease MUC1 more in parental cells than in acquired 17-AAG-resistant cells. Further study found that knockdown of MUC1 expression by small interfering RNA could obviously re-sensitize the resistant cells to 17-AAG treatment, and decrease the cell migration and adhesion. These were coupled with a downregulation in N-cadherin and β-catenin. The results indicate that HSP90 inhibitor therapies in colon carcinomas could generate resistance and increase metastatic potential that might mediated by upregulation of MUC1 expression. Findings from this study further our understanding of the potential clinical effects of HSP90-directed therapies in

  16. Biphasic increase of apical Cl- conductance by muscarinic stimulation of ht-29cl.19a human colon carcinoma cell line: Evidence for activation of different cl- conductances by carbachol and forskolin

    NARCIS (Netherlands)

    R.B. Bajnath (R.); K. Dekker (K.); A.B. Vaandrager (Arie); H.R. de Jonge (Hugo); J.A. Groot (J.)

    1992-01-01

    textabstractThe modulation of ion transport pathways in filtergrown monolayers of the Cl--secreting subclone (19A) of the human colon carcinoma cell line HT-29 by muscarinic stimulation was studied by combined Ussing chamber and microimpalement experiments. Basolateral addition of 10-4m carbachol

  17. Radioimmunoimaging of human colon carcinoma grafted into nudemice using 131I-labeled monoclonal anticea antibody and its F(ab')2 fragments

    International Nuclear Information System (INIS)

    Liu Guangda

    1988-01-01

    131 I-labeled monoclonal anti-CEA antibody and its F(ab') 2 fragments were injected into nude mice bearing human colon carcinoma xenografts for tumor localization and radioimmunoimaging studies. Transplanted tumors were visualized in 12 hours after injection of the labeled anti-CEA or its F(ab') 2 by gamma camera. Biodistribution data indicated that F(ab') 2 fragments were cleared more rapidly from blood (T 1/2 = 13.3 h for F(ab') 2 , T 1/2 = 21.1 h for intact antibody) over 6-24 h and had higher tumor blood ratios. The intact antibody was concentrated in the tumor better than F(ab') 2 . In double-label experiments, a nonspecific localization of the control ( 125 I-labeled anti-HCG) in the tumor was also observed

  18. A Rare Case of Undifferentiated Carcinoma of the Colon with Rhabdoid Features: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    E. Moussaly

    2015-01-01

    Full Text Available Malignant rhabdoid tumors were originally described in children. Subsequently, the same histological pattern was described in adults. Malignant rhabdoid tumors are aggressive neoplasms that have been reported in multiple organs. To our best knowledge, only 16 previous cases of rhabdoid tumor in the colon have been described in the literature. We present the case of an 87-year-old lady who was diagnosed with a rhabdoid tumor of the colon that relapsed rapidly after surgical resection. The literature concerning this unusual neoplasm was subsequently reviewed with comparison of all known cases in the literature.

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

    Directory of Open Access Journals (Sweden)

    Jaques Waisberg

    2002-07-01

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

  20. Effect of cisplatin and c-myb antisense phosphorothioate oligodeoxynucleotides combination on a human colon carcinoma cell line in vitro and in vivo.

    Science.gov (United States)

    Del Bufalo, D.; Cucco, C.; Leonetti, C.; Citro, G.; D'Agnano, I.; Benassi, M.; Geiser, T.; Zon, G.; Calabretta, B.; Zupi, G.

    1996-01-01

    We investigated the effect of c-myb antisense phosphorothioate oligodeoxynucleotides [(S)ODNs] and cisplatin (CDDP) combination on the human colon carcinoma cell line LoVo Dx both in vitro and in nude mice bearing LoVo Dx solid tumour. We show that antisense (S)ODN treatment decreases c-myb mRNA and protein expression, induces growth arrest in the G1 phase of the cell cycle, and inhibits cell proliferation. In vivo treatment with c-myb antisense (S)ODNs results in a reduction in tumour growth. A greater inhibition of cell proliferation in vitro and a higher increase of tumour growth inhibition and growth delay in vivo were obtained with the combination of (S)ODNs and CDDP than when the two agents were administered separately. This comparative study, using the same tumour cell line in vitro and in vivo, suggests that c-myb antisense (S)ODNs might be useful in the therapy of colon cancer in combination with antineoplastic drugs. Images Figure 1 Figure 4 PMID:8695353

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

    LENUS (Irish Health Repository)

    Alzamora, Rodrigo

    2011-01-01

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

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

    LENUS (Irish Health Repository)

    Alzamora, Rodrigo

    2012-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Rodrigo eAlzamora

    2011-06-01

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

  4. Akt Inhibitor MK2206 in Treating Patients With Previously Treated Colon or Rectal Cancer That is Metastatic or Locally Advanced and Cannot Be Removed by Surgery

    Science.gov (United States)

    2017-06-26

    Colon Mucinous Adenocarcinoma; Colon Signet Ring Cell Adenocarcinoma; Rectal Mucinous Adenocarcinoma; Rectal Signet Ring Cell Adenocarcinoma; Recurrent Colon Carcinoma; Recurrent Rectal Carcinoma; Stage IIIA Colon Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

  5. Changes in telomerase activity, expression and splicing in response to differentiation of normal and carcinoma colon cells

    Czech Academy of Sciences Publication Activity Database

    Fajkus, Jiří; Borský, M.; Kunická, Z.; Kovaříková, Martina; Dvořáková, D.; Hofmanová, Jiřina; Kozubík, Alois

    2003-01-01

    Roč. 23, 2B (2003), s. 1605-1612 ISSN 0250-7005 R&D Projects: GA AV ČR IPP1050128; GA ČR GA525/01/0419; GA AV ČR IBS5004010; GA MPO FD-K/033 Institutional research plan: CEZ:AV0Z5004920; CEZ:MSM 143100008 Keywords : telomerase regulation * human colon cells * butyrate Subject RIV: BO - Biophysics Impact factor: 1.347, year: 2003

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

    Science.gov (United States)

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

    2012-02-01

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

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

    OpenAIRE

    Li, Chun-Yan; Li, Bao-Xiu; Liang, Yi; Peng, Rui-Qing; Ding, Ya; Xu, Da-Zhi; Zhang, Xin; Pan, Zhi-Zhong; Wan, De-Sen; Zeng, Yi-Xin; Zhu, Xiao-Feng; Zhang, Xiao-Shi

    2009-01-01

    Abstract Background Cancer stem cell model suggested that tumor progression is driven by the overpopulation of cancer stem cells and eradicating or inhibiting the symmetric division of cancer stem cells would become the most important therapeutic strategy. However, clinical evidence for this hypothesis is still scarce. To evaluate the overpopulation hypothesis of cancer stem cells the association of percentage of CD133+ tumor cells with clinicopathological parameters in colon cancer was inves...

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

    Directory of Open Access Journals (Sweden)

    R. Vilallonga

    2008-01-01

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

  9. Oestrogen receptor beta isoform expression in sporadic colorectal cancer, familial adenomatous polyposis and progressive stages of colorectal cancer

    DEFF Research Database (Denmark)

    Stevanato Filho, Paulo Roberto; Aguiar Júnior, Samuel; Begnami, Maria Dirlei

    2017-01-01

    BACKGROUND: Among the sex hormones, oestrogen may play a role in colorectal cancer, particularly in conjunction with oestrogen receptor-β (ERβ). The expression of ERβ isoform variants and their correlations with familial adenomatous polyposis (FAP) syndrome and sporadic colorectal carcinomas are ...... provide a better understanding of oestrogens and their potential preventive and therapeutic effects on sporadic colorectal cancer and cancers associated with FAP syndrome.......BACKGROUND: Among the sex hormones, oestrogen may play a role in colorectal cancer, particularly in conjunction with oestrogen receptor-β (ERβ). The expression of ERβ isoform variants and their correlations with familial adenomatous polyposis (FAP) syndrome and sporadic colorectal carcinomas...... was identified in sporadic polyps and in sporadic colorectal cancer as well as in polyps from FAP syndrome patients compared with normal tissues (p

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

    Directory of Open Access Journals (Sweden)

    Wan-Chi Lee

    2011-01-01

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

  11. Tratamiento y post-tratamiento con lonidamina en la línea celular de carcinoma colónico humano HT-29 Treatment and post-treatment with lonidamine in human colon carcinoma HT-29 cell line

    Directory of Open Access Journals (Sweden)

    Alicia G. Fuchs

    2008-02-01

    Full Text Available Lonidamina (1-[ 2,4-diclorofenil metil]-1H indazol-3-ácido carboxílico, (lnd, es una droga antineoplásica cuyo mecanismo de acción se ejerce sobre el metabolismo intermedio de la glucosa. Los efectos de la lnd sobre el crecimiento celular y el metabolismo celular se investigaron en las células HT- 29, línea celular de carcinoma colónico humano, que requiere altas concentraciones de glucosa para su crecimiento indiferenciado en cultivo. La lnd en dosis de 0.2 mM disminuyó significativamente el crecimiento celular y la formación de colonias en agar; con la interrupción del tratamiento se observó el restablecimiento del crecimiento celular en 24 horas. El tratamiento con lnd produce la redistribución de los glicoconjugados y el receptor de la manosa, sin afectar en forma drástica la síntesis de glucógeno ni la de proteínas. Estas posiblemente sean las causas de la rápida reversibilidad del tratamiento.Lonidamine (1-[ 2,4-dichlorophenyl methyl]-1H indazole-3-carboxylic acid, lnd, is an antitumoral drug acting on mitochondria and glucose metabolism. Cell growth and metabolic effects of lnd and drug post-treatment effect were investigated in undifferentiated HT-29 human colonic carcinoma cell line which requires high glucose medium concentration for growth. 0.2 mM lnd significantly decreased cell spreading and growth in monolayer or agar cell culture. After drug treatment cell growth was reestablished to control value within 24 h. Ind modified glycoconjugates and mannose-receptor distribution (analyzed by confocal microscopy, while glucose-glycogen and protein synthesis were not affected, these being the possible reasons for the fast reversible effect.

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

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    Zhang Xin

    2009-07-01

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

  13. In vitro and in vivo anticancer effects of singly protonated dehydronorcantharidin silver coordination polymer in CT-26 murine colon carcinoma model.

    Science.gov (United States)

    Jin, Xing; Tan, Xuejie; Zhang, Xiumei; Han, Mingyong; Zhao, Yunxue

    2015-10-15

    Silver complexes are active constituents of the metal-based compounds; several studies suggest that silver complexes possess antimicrobial and anticancer properties. We have recently reported that Ag-SP-DNC, a novel silver and singly protonated dehydronorcantharidin complex, triggers oxidative stress-mediated apoptosis of lung cancer cells. In this study, we investigated the anticancer effects of Ag-SP-DNC in CT-26 murine colon carcinoma model. Ag-SP-DNC induced apoptosis of CT-26 cells, together with inhibition of cell proliferation; treatment of CT-26 tumor-bearing mice with Ag-SP-DNC delayed tumor growth. We also explored the mechanism of action of Ag-SP-DNC and found that Ag-SP-DNC treatment of CT-26 cells was associated with high levels of intracellular reactive oxygen species. The further experiments revealed that Ag-SP-DNC-treated cells underwent loss of mitochondrial membrane potential concomitant with intracellular calcium overload and caspase-3 activation. Taken together, our study demonstrates the potent anticancer effects of Ag-SP-DNC to colorectal cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Koelreuteria Formosana Extract Induces Growth Inhibition and Cell Death in Human Colon Carcinoma Cells via G2/M Arrest and LC3-II Activation-Dependent Autophagy.

    Science.gov (United States)

    Horng, Chi-Ting; Wu, Yueh-Jung; Chen, Pei-Ni; Chu, Shu-Chen; Tsai, Chun-Miao; Hsieh, Yih-Shou

    2017-01-01

    Autophagy is a self-destructive process that degrades cytoplasmic constituents. In our previous study, Koelreuteria formosana ethanolic extract (KFEE), which is obtained from natural plants endemic to Taiwan, has inhibited cell metastasis in renal carcinoma cells. However, the anticancer effects of KFEE on colon cancer remain unclear. In this study, KFEE exerted a strong cytotoxic effect on DLD-1 and COLO 205 human colorectal cancer cell lines. KFEE effectively inhibited cancer cell proliferation, induced G2/M-phase arrest associated with downregulaton of cyclin E, cyclin B and cdc25C and upregulation of p21, and induced cell death by activating autophagy but did not cause apoptotic cell death. Exposed KFEE cells showed increased levels of acridine orange, autophagic vacuoles, and LC3-II proteins, which are specific autophagic markers. Bcl-2, p-Akt, and p-mTOR levels, which have been implicated in autophagic downregulation, were decreased after KFEE treatment. Autophagy inhibitor 3-methyladenosine and bafilomycin-A1 and genetic silencing of LC3 attenuated KFEE-induced growth inhibition. These findings suggested that KFEE causes cytostatic effect through autophagy. In xenograft studies, oral administration of KFEE had significantly inhibited the tumor growth in nude mice that had received subcutaneous injection of DLD-1 cells. KFEE is a promising candidate in phytochemical-based, mechanistic, and pathway-targeted cancer prevention strategies.

  15. Expression of radiation damage in two tumor subpopulations obtained from a heterogeneous human colon carcinoma as a function of growth state

    International Nuclear Information System (INIS)

    Arundel, C.M.; Leith, J.T.

    1984-01-01

    The authors have defined changes in intrinsic x-ray (100 kVp) radiation sensitivity that occur when human tumor cells are grown either exponentially, or as plateau (both fed and unfed) phase cultures in vitro. Two subpopulations of a human colon carcinoma were studied (clones A and D), and values for single hit, multitarget inactivation were obtained. For clone A the n, D/sub o/ (Gy), and D/sub q/ (Gy) values for exponential cells were 8.2, 1.06, and 2.23. For clone D, these values were 5.8, 1.08, and 2.23. For fed plateau phase cultures the clone A values were 18.4, 0.86, and 2.52, while for fed clone D cells these values were 16.1, 0.80, and 2.24. For unfed plateau phase cultures the clone A values were 28.5, 0.71, and 2.40, while for unfed clone D cells these values were 15.5, 0.76, and 2.10. These data indicate that the major change in intrinsic radiation sensitivity of these heterogeneous tumor subpopulations is the increase in the number of lesions per unit dose produced in plateau phase cells. Complete studies of repair of potentially lethal damage in these 2 tumor lines are being done to fully define radiation responses in plateau phase cultures

  16. Photocatalytic Inactivation Effect of Gold-Doped TiO2 (Au/TiO2 Nanocomposites on Human Colon Carcinoma LoVo Cells

    Directory of Open Access Journals (Sweden)

    Zhiyu Jiang

    2007-11-01

    Full Text Available The photocatalytic inactivation effecting of gold-doped TiO2 (Au/TiO2 nanocomposites on human colon carcinoma LoVo cells was investigated for the first time. The Au/TiO2 samples containing different amounts of Au (1–4 wt% were prepared by deposition-precipitation (DP method. These synthesized Au/TiO2 nanocomposites were characterized by transmission electron microscopy (TEM and inductively coupled plasma atomic emission spectroscopy. It was found that the photocatalytic inactivation effect of TiO2 nanoparticles on LoVo cancer cells could be greatly improved by the surface modification of Au nanoparticles. Furthermore, the loading amount of Au on the surface of TiO2 nanoparticles affects the photocatalytic inactivation efficiency strongly, and it was found that the most efficient nanocomposites were TiO2 nanoparticles doped with 2 wt% Au. When 50 μg/mL 2 wt% Au/TiO2 nanocomposites were used, all of the LoVo cancer cells were killed under the irradiation of UV light (λmax = 365 nm, Intensity = 1.8 mW/cm2 within 100 minutes. But for 50 μg/mL TiO2 nanoparticles, only 40% cancer cells were killed under the same condition.

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

    Science.gov (United States)

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

    2012-03-01

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

  18. MAJOR MOLECULAR GENETIC DRIVERS IN SPORADIC PRIMARY HYPERPARATHYROIDISM.

    Science.gov (United States)

    Arnold, Andrew

    2016-01-01

    Primary hyperparathyroidism is primarily due to a solitary parathyroid adenoma but multi-gland disease, parathyroid carcinoma, and ectopic parathyroid hormone production can occur. Although primary hyperparathyroidism mostly presents sporadically, strong familial predispositions also exist. Much is known about heritable genetic mutations responsible for these syndromes, including multiple endocrine neoplasia types 1 and 2A, hyperparathyroidism-jaw tumor syndrome, and familial hypocalciuric hypercalcemia. Acquired mutations in common sporadic hyperparathyroidism have also been discovered. Here we focus on the most common and well-established genetic drivers: 1) involvement of the oncogene cyclin D1 in human neoplasia was first established in parathyroid adenomas, followed by recognition of its importance in other tumor types including breast cancer and B-lymphoid malignancy; and 2) somatic mutation of the MEN1 gene, first identified as the source of pathogenic germline mutations in patients with familial endocrinopathies, is found in a substantial fraction of non-familial parathyroid adenomas.

  19. Red meat and colon cancer : a possible role for heme

    NARCIS (Netherlands)

    Sesink, Aloysius Lambertus Antonia

    2000-01-01

    Sporadic colon cancer is a multifactorial aging disease affected by long-term exposure to environmental risk factors. Epidemiological studies have shown that risk for colon cancer is associated with diets high in red meat and/or animal fat. The mechanisms by which colonic tumors arise are, however,

  20. Chitosan oligosaccharides with degree of polymerization 2-6 induces apoptosis in human colon carcinoma HCT116 cells.

    Science.gov (United States)

    Zou, Pan; Yuan, Shoujun; Yang, Xin; Zhai, Xingchen; Wang, Jing

    2018-01-05

    Colon cancer is the third most common cancer, and yet there is a lack of effective therapeutic method with low side effects. Chitosan oligosaccharides (COS) is derived from chitosan after chitin deacetylation, and attracts more interests due to smaller molecular weight and soluble property. Previously, COS, mainly absorbed through intestinal epithelia, has been reported to exhibit many bioactivities, especially its anti-tumor effect. Recent references pay little attention to molecular weight distribution which is crucial for understanding its biological behavior. Here, we studied reducing sugar content and degree of polymerization (DP) of COS. 86.73% reducing sugar exists in COS sample and the content of chitosan fractions with 2-6 is 85.8%. COS suppressed the growth of HCT116 cells in vitro and in vivo, and the inhibition rate of tumor weight in vivo was high up to 58.6%. Moreover, the morphology observation, flow cytometry analysis and mRNA expression were applied to study the apoptosis related mechanism. COS treatment promoted mitosis, late stage apoptosis and S cell cycle arrest in HCT116 cells, and enhanced the mRNA expression of BAK and reduce BCL-2 and BCL-x L . These findings may provide an important clue for clinical applications of COS as anti-tumor drug or pharmaceutic adjuvant in the future. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Distinct nuclear arrangement of active and inactive c-myc genes in control and differentiated colon carcinoma cells

    International Nuclear Information System (INIS)

    Harnicarova, Andrea; Kozubek, Stanislav; Pachernik, Jiri; Krejci, Jana; Bartova, Eva

    2006-01-01

    Using sequential RNA-DNA fluorescence in situ hybridization, the nuclear arrangement of both the active and inactive c-myc gene as well as its transcription was investigated in colon cancer HT-29 cells induced to differentiate into enterocytes. Cytogenetic studies revealed the presence of two chromosomes 8 in HT-29 cells, of which the one containing c-myc gene amplicons was substantially larger and easily distinguished from the normal chromosome. This observation enabled detection of both activity and nuclear localization of c-myc genes in single cells and in individual chromosome territories. Similar transcriptional activity of the c-myc gene was observed in both the normal and derivative chromosome 8 territories showing no influence of the amplification on the c-myc gene expression. Our experiments demonstrate strikingly specific nuclear and territorial arrangements of active genes as compared with inactive ones: on the periphery of their territories facing to the very central region of the cell nucleus. Nuclear arrangement of c-myc genes and transcripts was conserved during cell differentiation and, therefore, independent of the level of differentiation-specific c-myc gene expression. However, after the induction of differentiation, a more internal territorial location was found for the single copy c-myc gene of normal chromosome 8, while amplicons conserved their territorial topography

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

    Directory of Open Access Journals (Sweden)

    van Duivendijk Peter

    2010-06-01

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

  3. BRCA promoter methylation in sporadic versus BRCA germline mutation-related breast cancers.

    Science.gov (United States)

    Vos, Shoko; Moelans, Cathy Beatrice; van Diest, Paul Joannes

    2017-05-31

    In breast cancer, BRCA promoter hypermethylation and BRCA germline mutations are said to occur together rarely, but this property has not yet been translated into a clinical test. Our aim in this study was to investigate the diagnostic value of BRCA1/2 methylation in distinguishing breast carcinomas of BRCA1 and BRCA2 germline mutation carriers from sporadic breast carcinomas using a recently developed BRCA methylation assay based on methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). MS-MLPAs were performed to assess BRCA1 and BRCA2 methylation in breast carcinoma tissues from 39 BRCA1 and 33 BRCA2 germline mutation carriers, 80 patients with sporadic breast cancer, and normal breast tissues from 5 BRCA1 and 4 BRCA2 mutation carriers and 5 nonmutation carriers. Methylation frequencies varied considerably between CpG sites across the BRCA1 and BRCA2 promoters. Some CpG sites were methylated more frequently in BRCA1/2-related than in sporadic carcinomas, whereas other CpG sites were methylated more frequently in sporadic carcinomas, with large variances in sensitivity and specificity as a consequence. The diagnostic value of BRCA promoter methylation analysis in distinguishing BRCA1/2-related from sporadic breast carcinomas seems to be considerably dependent on the targeted CpG sites. These findings are important for adequate use of BRCA methylation analysis as a prescreening tool for BRCA germline genetic testing or to identify BRCAness patients who may benefit from targeted therapies such as poly(adenosine diphosphate-ribose) polymerase inhibitors.

  4. Assessment of Blood Hemodynamics by USPIO-Induced R1 Changes in MRI of Murine Colon Carcinoma

    Science.gov (United States)

    van Laarhoven, H. W. M.; Philippens, M.; Peeters, W. J. M.; Rijken, P.; van der Kogel, A.; Punt, C. J. A.; Heerschap, A.

    2010-01-01

    The objective of this study is to assess whether ultrasmall superparamagnetic iron oxide (USPIO)-induced changes of the water proton longitudinal relaxation rate (R1) provide a means to assess blood hemodynamics of tumors. Two types of murine colon tumors (C26a and C38) were investigated prior to and following administration of USPIO blood-pool contrast agent with fast R1 measurements. In a subpopulation of mice, R1 was measured following administration of hydralazine, a well-known blood hemodynamic modifier. USPIO-induced R1 increase in C38 tumors (ΔR1 = 0.072 ± 0.0081 s−1) was significantly larger than in C26a tumors (ΔR1 = 0.032 ± 0.0018 s−1, N = 9, t test, P < 0.001). This was in agreement with the immunohistochemical data that showed higher values of relative vascular area (RVA) in C38 tumors than in C26a tumors (RVA = 0.059 ± 0.015 vs. 0.020 ± 0.011; P < 0.05). Following administration of hydralazine, a decrease in R1 value was observed. This was consistent with the vasoconstriction induced by the steal effect mechanism. In conclusion, R1 changes induced by USPIO are sensitive to tumor vascular morphology and to blood hemodynamics. Thus, R1 measurements following USPIO administration can give novel insight into the effects of blood hemodynamic modifiers, non-invasively and with a high temporal resolution. PMID:20502507

  5. KCNQ1OT1 hypomethylation: A Novel disguised genetic predisposition in sporadic pediatric adrenocortical tumors?

    NARCIS (Netherlands)

    Wijnen, Mark; Alders, Mariëlle; Zwaan, Christian M.; Wagner, Anja; van den Heuvel-Eibrink, Marry M.

    2012-01-01

    Pediatric adrenal tumors, other than neuroblastoma, are rare and can be associated with a genetic predisposition. In this report we describe two patients with an isolated and apparently sporadic adrenocortical tumor; one girl with a carcinoma, the other girl with an adenoma. In both patients genetic

  6. Ablation of human colon carcinoma in nude mice by 131I-labeled monoclonal anti-carcinoembryonic antigen antibody F(ab')2 fragments

    International Nuclear Information System (INIS)

    Buchegger, F.; Pfister, C.; Fournier, K.; Prevel, F.; Schreyer, M.; Carrel, S.; Mach, J.P.

    1989-01-01

    Pooled F(ab')2 fragments of three MAbs against distinct epitopes of carcinoembryonic antigen (CEA) were used for radioimmunotherapy of nude mice bearing a subcutaneous human colon carcinoma xenograft. 9-10 d after transplantation when tumor nodules were in exponential growth, 36 mice were treated by intravenous injection of different amounts of 131 I-labeled MAb F(ab')2. All 14 mice injected with a single dose of 2,200 (n = 10) or 2,800 microCi (n = 4) showed complete tumor remission. 8 of the 10 mice treated with 2,200 microCi survived in good health for 1 yr when they were killed and shown to be tumor free. Four of nine other mice treated with four fractionated doses of 400 microCi showed no tumor relapse for more than 9 mo. In contrast, all 15 mice injected with 1,600-3,000 microCi 131 I-control IgG F(ab')2 showed tumor growth retardation of only 1-4 wk, and 15 of 16 mice injected with unlabeled anti-CEA MAb F(ab')2 showed unmodified tumor progression as compared with untreated mice. From tissue radioactivity distributions it was calculated that by an injection of 2,200 microCi 131 I-MAb F(ab')2 a mean dose of 8,335 rad was selectively delivered to the tumor, while the tissue-absorbed radiation doses for the normal organs were: peripheral blood, 2,093; stomach, 1,668; kidney, 1,289; lung, 1,185; liver, 617; spleen, 501; small intestine, 427; large intestine, 367; bone, 337; and muscle, 198. These treatments were well tolerated since out of 19 mice with complete tumor remission only 4 required bone marrow transplantation and 17 were in good health for 6-12 mo of observation

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

    Science.gov (United States)

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

    2016-01-01

    Objectives Immunohistochemistry for DNA mismatch repair proteins is used to screen for Lynch syndrome in individuals with colorectal carcinoma (CRC). Although solitary loss of PMS2 expression is indicative of carrying a germline mutation in PMS2, previous studies reported MLH1 mutation in some cases. We determined the prevalence of MLH1 germline mutations in a large cohort of individuals with a CRC demonstrating solitary loss of PMS2 expression. Design This cohort study included 88 individuals affected with a PMS2-deficient CRC from the Colon Cancer Family Registry Cohort. Germline PMS2 mutation analysis (long-range PCR and multiplex ligation-dependent probe amplification) was followed by MLH1 mutation testing (Sanger sequencing and multiplex ligation-dependent probe amplification). Results Of the 66 individuals with complete mutation screening, we identified a pathogenic PMS2 mutation in 49 (74%), a pathogenic MLH1 mutation in 8 (12%) and a MLH1 variant of uncertain clinical significance predicted to be damaging by in silico analysis in 3 (4%); 6 (9%) carried variants likely to have no clinical significance. Missense point mutations accounted for most alterations (83%; 9/11) in MLH1. The MLH1 c.113A> G p.Asn38Ser mutation was found in 2 related individuals. One individual who carried the MLH1 intronic mutation c.677+3A>G p.Gln197Argfs*8 leading to the skipping of exon 8, developed 2 tumours, both of which retained MLH1 expression. Conclusions A substantial proportion of CRCs with solitary loss of PMS2 expression are associated with a deleterious MLH1 germline mutation supporting the screening for MLH1 in individuals with tumours of this immunophenotype, when no PMS2 mutation has been identified. PMID:26895986

  8. Diet, microbiota, and microbial metabolites in colon cancer risk in rural Africans and African Americans

    NARCIS (Netherlands)

    Ou, J.; Carbonero, F.; Zoetendal, E.G.; Delany, J.P.; Wang, M.; Newton, K.; Gaskins, H.R.; O'Keefe, S.F.

    2013-01-01

    BACKGROUND: Epidemiologic studies have suggested that most cases of sporadic colon cancer can be attributed to diet. The recognition that colonic microbiota have a major influence on colonic health suggests that they might mediate colonic carcinogenesis. OBJECTIVE: To examine the hypothesis that the

  9. Endocardite infecciosa por Streptococcus bovis em paciente com carcinoma colônico Endocarditis infecciosa por Streptococcus bovis en paciente con carcinoma colónico Infectious endocarditis due to Streptococcus bovis in a patient with colon carcinoma

    Directory of Open Access Journals (Sweden)

    Alexandre Maulaz Barcelos

    2010-09-01

    Full Text Available Descrevemos o caso de uma paciente de 66 anos de idade, com endocardite infecciosa por Streptococcus bovis e adenocarcinoma colônico, que desenvolveu insuficiência aórtica grave aguda. Foi submetida à cirurgia de troca valvar aórtica e posteriormente à ressecção tumoral (hemicolectomia direita. É importante ressaltar a necessidade de complementação do estudo do cólon, mesmo em indivíduos assintomáticos, quando diagnosticamos endocardite infecciosa por S. bovis.Describimos el caso de una paciente de 66 años de edad, con endocarditis infecciosa por streptococcus bovis y adenocarcinoma colónico, que desarrolló insuficiencia aórtica grave aguda. Fue sometida a cirugía de reemplazo valvular aórtico y posteriormente a resección tumoral (hemicolectomía derecha. Es importante destacar la necesidad de complementación del estudio del colon, aun en individuos asintomáticos, cuando diagnosticamos endocarditis infecciosa por S. bovis.We report the case of a 66 year-old female patient with infectious endocarditis due to Streptococcus bovis and adenocarcinoma of the colon that developed acute aortic insufficiency. She was submitted to aortic valve replacement surgery and later to tumor resection (right hemicolectomy. It is important to emphasize the need for complementing the study of the colon, even in asymptomatic individuals, when infectious endocarditis due to S. bovis is diagnosed.

  10. Colonic Polyps

    Science.gov (United States)

    ... Colonic polyps grow in the large intestine, or colon. Most polyps are not dangerous. However, some polyps ... member with polyps Have a family history of colon cancer Most colon polyps do not cause symptoms. ...

  11. Relationship among mismatch repair deficiency, CDX2 loss, p53 and E-cadherin in colon carcinoma and suitability of using a double panel of mismatch repair proteins by immunohistochemistry.

    Science.gov (United States)

    Sayar, Ilyas; Akbas, Emin Murat; Isik, Arda; Gokce, Aysun; Peker, Kemal; Demirtas, Levent; Gürbüzel, Mehmet

    2015-09-01

    Biomarkers such as mismatch repair proteins, CDX2, p53, and E-cadherin are blamed for colon cancers, but the relationships of these biomarkers with each other and with pathological risk factors in colon carcinoma are still not clear. The aim of this study was to evaluate the association of these biomarkers with each other by using immunohistochemical staining and to compare their expression with pathological risk factors for colonic adenocarcinoma. We also aimed to study the usability of a double panel of mismatch repair proteins. One hundred and eleven cases with colonic adenocarcinoma were examined. There was a statistically significant relationship between tumor histological differentiation and perineural invasion, vascular invasion, mismatch repair deficiency, p53, CDX2, and E-cadherin (p mismatch repair deficiency. Mismatch repair deficiency was correlated with CDX2 loss and E-cadherin expression (p mismatch repair deficiency. Association of CDX2 and PMS2 in the present study is necessary to conduct further genetic and pathological studies focusing on these two markers together.

  12. Adult onset sporadic ataxias: a diagnostic challenge

    Directory of Open Access Journals (Sweden)

    Orlando Graziani Povoas Barsottini

    2014-03-01

    Full Text Available Patients with adult onset non-familial progressive ataxia are classified in sporadic ataxia group. There are several disease categories that may manifest with sporadic ataxia: toxic causes, immune-mediated ataxias, vitamin deficiency, infectious diseases, degenerative disorders and even genetic conditions. Considering heterogeneity in the clinical spectrum of sporadic ataxias, the correct diagnosis remains a clinical challenge. In this review, the different disease categories that lead to sporadic ataxia with adult onset are discussed with special emphasis on their clinical and neuroimaging features, and diagnostic criteria.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-01-15

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

  14. Imaging the colon

    International Nuclear Information System (INIS)

    Kelvin, F.M.; Thompson, W.M.

    1987-01-01

    Radiographic techniques, particularly the barium enema, remain crucial in the evaluation of the colon despite the development of colonscopy. There is still controversy concerning the optimal method of performing the barium enema examination. This course includes a discussion of the respective roles of double-and single-contrast barium examinations as well as the technical aspects of their performance. The roles of other colon imaging modalities are discussed, with particular emphasis on the increasing value of CT. The various manifestations and differential diagnosis of inflammatory bowel disease, including diverticulitis, are presented. The radiologic evaluation and appearances of colorectal carcinoma and adenomatous polyps are discussed, as are some of the pitfalls in their diagnosis. The emphais of the presentation is on practical aspects of imaging the colon, and the varying appearances seen in the more common colon diseases

  15. Monitoring early response to anti-angiogenic therapy: diffusion-weighted magnetic resonance imaging and volume measurements in colon carcinoma xenografts.

    Directory of Open Access Journals (Sweden)

    Moritz Jörg Schneider

    Full Text Available OBJECTIVES: To evaluate the use of diffusion-weighted MRI (DW-MRI and volume measurements for early monitoring of antiangiogenic therapy in an experimental tumor model. MATERIALS AND METHODS: 23 athymic nude rats, bearing human colon carcinoma xenografts (HT-29 were examined before and after 6 days of treatment with regorafenib (n = 12 or placebo (n = 11 in a clinical 3-Tesla MRI. For DW-MRI, a single-shot EPI sequence with 9 b-values (10-800 s/mm2 was used. The apparent diffusion coefficient (ADC was calculated voxelwise and its median value over a region of interest, covering the entire tumor, was defined as the tumor ADC. Tumor volume was determined using T2-weighted images. ADC and volume changes between first and second measurement were evaluated as classifiers by a receiver-operator-characteristic (ROC analysis individually and combined using Fisher's linear discriminant analysis (FLDA. RESULTS: All ADCs and volumes are stated as median±standard deviation. Tumor ADC increased significantly in the therapy group (0.76±0.09×10(-3 mm2/s to 0.90±0.12×10(-3 mm2/s; p<0.001, with significantly higher changes of tumor ADC than in the control group (0.10±0.11×10(-3 mm2/s vs. 0.03±0.09×10(-3 mm2/s; p = 0.027. Tumor volume increased significantly in both groups (therapy: 347.8±449.1 to 405.3±823.6 mm3; p = 0.034; control: 219.7±79.5 to 443.7±141.5 mm3; p<0.001, however, the therapy group showed significantly reduced tumor growth (33.30±47.30% vs. 96.43±31.66%; p<0.001. Area under the curve and accuracy of the ADC-based ROC analysis were 0.773 and 78.3%; and for the volume change 0.886 and 82.6%. The FLDA approach yielded an AUC of 0.985 and an accuracy of 95.7%. CONCLUSIONS: Regorafenib therapy significantly increased tumor ADC after 6 days of treatment and also significantly reduced tumor growth. However, ROC analyses using each parameter individually revealed a lack of accuracy in discriminating between therapy and

  16. Mutation analysis of the RET gene in individuals with sporadic and familial pheochromocytoma

    Energy Technology Data Exchange (ETDEWEB)

    Iyengar, S.; Sirugo, G.; Bale, A.E. [Yale Univ. School of Medicine, New Haven, CT (United States)] [and others

    1994-09-01

    Pheochromocytoma is common to many familial cancer syndromes including multiple endocrine neoplasia type 2A (MEN2A), von Hippel-Lindau (VHL) and neurofibromatosis (NF). Although sporadic cases of pheochromocytoma have been examined for mutations in exons 10, 11 and 16 of the RET gene, only one case with a mutation in exon 16 has been reported thus far. We are performing systematic examination of exons of the RET gene, which has previously been associated with mutation in both MEN2 A and B, to determine the role RET may play in the etiology of pheochromocytoma. Seventeen cases of sporadic pheochromocytoma and 3 cases of sporadic medullary thyroid carcinoma were obtained from the pathology archives. Histopathology of all specimens was confirmed to be either pheochromocytoma or medullary thyroid carcinoma before DNA was extracted from 0.5{mu} thin sections of paraffin-embedded tissue. DNA from familial pheochromocytoma patients was also available for analysis. All sporadic and familial cases were amplified for exons 2, 6 and 16 of the RET gene. Single strand conformational polymorphism (SSCP) analysis was performed for exons 2 and 6. On finding a variation in the SSCP pattern in the pheochromocytoma kindred we sequenced all the samples for exon 2. A single base pair variation was found, which did not segregate with pheochromocytoma in the family. No variant SSCP patterns have been observed with the exon 6 PCR products thus far. Exon 16 PCR products were subjected to DNA restriction analysis with Fok I. This enzyme detects a single base pair change associated with MEN2 B. With the exception of one sample with sporadic medullary thyroid carcinoma, all samples showed the normal pattern on DNA restriction analysis. Thus we can exclude exons 2 and 6 of the RET gene in the pathogenesis of pheochromocytoma. SSCP analyses with other exons in the RET gene are underway.

  17. Diagnostic role of barium enema in carcinoma rectum

    International Nuclear Information System (INIS)

    Asghar, M.

    2003-01-01

    Objective: The main aim of this barium enema study was to evaluate its role in patients suspected to have rectal pathologies with complaints of change in bowel habit, anorexia/weight loss, bleeding per rectum and acute/sub-acute colonic obstruction. Results: barium enema study as screening test for colo-rectal carcinoma was undertaken. Contrast outlined the colonic growth in 35 cases, out of which the cases of carcinoma colon were 24 including 13 patients suffering from carcinoma rectum. The percentage of carcinoma colon to total colonic growth was 68% while, carcinoma rectum to total carcinoma colon was 54%. Conclusion: On the basis of these investigations, it is concluded that patient's compliance is important factor in the early detection of colonic neoplasia. Though results of colonoscopy are more reliable but in practice, barium enema (double contrast) is performed initially to outline the lesion and then colonoscopy for biopsy purpose. (author)

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

    Science.gov (United States)

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

    1998-06-01

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

  19. BRCAness profile of sporadic ovarian cancer predicts disease recurrence.

    Directory of Open Access Journals (Sweden)

    Weiya Z Wysham

    Full Text Available The consequences of defective homologous recombination (HR are not understood in sporadic ovarian cancer, nor have the potential role of HR proteins other than BRCA1 and BRCA2 been clearly defined. However, it is clear that defects in HR and other DNA repair pathways are important to the effectiveness of current therapies. We hypothesize that a subset of sporadic ovarian carcinomas may harbor anomalies in HR pathways, and that a BRCAness profile (defects in HR or other DNA repair pathways could influence response rate and survival after treatment with platinum drugs. Clinical availability of a BRCAness profile in patients and/or tumors should improve treatment outcomes.To define the BRCAness profile of sporadic ovarian carcinoma and determine whether BRCA1, PARP, FANCD2, PTEN, H2AX, ATM, and P53 protein expression correlates with response to treatment, disease recurrence, and recurrence-free survival.Protein microarray analysis of ovarian cancer tissue was used to determine protein expression levels for defined DNA repair proteins. Correlation with clinical and pathologic parameters in 186 patients with advanced stage III-IV and grade 3 ovarian cancer was analyzed using Chi square, Kaplan-Meier method, Cox proportional hazard model, and cumulative incidence function.High PARP, FANCD2 and BRCA1 expressions were significantly correlated with each other; however, elevated p53 expression was associated only with high PARP and FANCD2. Of all patients, 9% recurred within the first year. Among early recurring patients, 41% had high levels of PARP, FANCD2 and P53, compared to 19.5% of patients without early recurrence (p = 0.04. Women with high levels of PARP, FANCD2 and/or P53 had first year cumulative cancer incidence of 17% compared with 7% for the other groups (P = 0.03.Patients with concomitantly high levels of PARP, FANCD2 and P53 protein expression are at increased risk of early ovarian cancer recurrence and platinum resistance.

  20. Antrodia camphorata grown on germinated brown rice inhibits HT-29 human colon carcinoma proliferation through inducing G0/G1 phase arrest and apoptosis by targeting the β-catenin signaling.

    Science.gov (United States)

    Park, Dong Ki; Lim, Yoong Ho; Park, Hye-Jin

    2013-08-01

    Antrodia camphorata (AC) has been used as a traditional medicine to treat food and drug intoxication, diarrhea, abdominal pain, hypertension, pruritis (skin itch), and liver cancer in East Asia. In this study, we investigated anticancer activities of AC grown on germinated brown rice (CBR) in HT-29 human colon cancer cells. We found that the inhibitory efficacy of CBR 80% ethanol (EtOH) extract on HT-29 and CT-26 cell proliferation was more effective than ordinary AC EtOH 80% extract. Next, 80% EtOH extract of CBR was further separated into four fractions; hexane, ethyl acetate (EtOAc), butanol (BuOH), and water. Among them, CBR EtOAc fraction showed the strongest inhibitory activity against HT-29 cell proliferation. Therefore, CBR EtOAc fraction was chosen for further studies. Annexin V-fluorescein isothiocyanate staining data indicated that CBR EtOAc fraction induced apoptosis. Induction of G0/G1 cell cycle arrest on human colon carcinoma cell was observed in CBR EtOAc fraction-treated cells. We found that CBR decreased the level of proteins involved in G0/G1 cell cycle arrest and apoptosis. CBR EtOAc fraction inhibited the β-catenin signaling pathway, supporting its suppressive activity on the level of cyclin D1. High performance liquid chromatography analysis data indicated that CBR EtOAc fraction contained adenosine. This is the first investigation that CBR has a greater potential as a novel chemopreventive agent than AC against colon cancer. These data suggest that CBR might be useful as a chemopreventive agent against colorectal cancer.

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

    Directory of Open Access Journals (Sweden)

    Olesia S. Vishchuk

    2013-01-01

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

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

    NARCIS (Netherlands)

    Scherphof, GL; Kamps, JAAM; Koning, GA

    1997-01-01

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

  3. TGF-beta receptor 2 downregulation in tumour-associated stroma worsens prognosis and high-grade tumours show more tumour-associated macrophages and lower TGF-beta1 expression in colon carcinoma: a retrospective study

    Directory of Open Access Journals (Sweden)

    Papadopoulos Thomas

    2007-08-01

    Full Text Available Abstract Background Histological phenotype and clinical behaviour of malignant tumours are not only dependent on alterations in the epithelial cell compartment, but are affected by their interaction with inflammatory cells and tumour-associated stroma. Studies in animal models have shown influence of tumour-associated macrophages (TAM on histological grade of differentiation in colon carcinoma. Disruption of transforming growth factor beta (TGF-beta signalling in tumour cells is related to more aggressive clinical behaviour. Expression data of components of this pathway in tumour-associated stroma is limited. Methods Tissue micro arrays of 310 colon carcinomas from curatively resected patients in UICC stage II and III were established. In a first step we quantified amount of CD68 positive TAMs and expression of components of TGF-beta signalling (TGF-beta1, TGF-beta receptors type 1 and 2, Smad 3 and 4 in tumour and associated stroma. Further we analyzed correlation to histological and clinical parameters (histological grade of differentiation (low-grade (i.e. grade 1 and 2 vs. high-grade (i.e. grade 3 and 4, lymph node metastasis, distant metastasis, 5 year cancer related survival using Chi-square or Fisher's exact test, when appropriate, to compare frequencies, Kaplan-Meier method to calculate 5-year rates of distant metastases and cancer-related survival and log rank test to compare the rates of distant metastases and survival. To identify independent prognostic factors Cox regression analysis including lymph node status and grading was performed. Results High-grade tumours and those with lymph node metastases showed higher rates of TAMs and lower expression of TGF-beta1. Loss of nuclear Smad4 expression in tumor was associated with presence of lymph node metastasis, but no influence on prognosis could be demonstrated. Decrease of both TGF-beta receptors in tumour-associated stroma was associated with increased lymph node metastasis and

  4. TGF-beta receptor 2 downregulation in tumour-associated stroma worsens prognosis and high-grade tumours show more tumour-associated macrophages and lower TGF-beta1 expression in colon carcinoma: a retrospective study

    International Nuclear Information System (INIS)

    Bacman, David; Merkel, Susanne; Croner, Roland; Papadopoulos, Thomas; Brueckl, Wolfgang; Dimmler, Arno

    2007-01-01

    Histological phenotype and clinical behaviour of malignant tumours are not only dependent on alterations in the epithelial cell compartment, but are affected by their interaction with inflammatory cells and tumour-associated stroma. Studies in animal models have shown influence of tumour-associated macrophages (TAM) on histological grade of differentiation in colon carcinoma. Disruption of transforming growth factor beta (TGF-beta) signalling in tumour cells is related to more aggressive clinical behaviour. Expression data of components of this pathway in tumour-associated stroma is limited. Tissue micro arrays of 310 colon carcinomas from curatively resected patients in UICC stage II and III were established. In a first step we quantified amount of CD68 positive TAMs and expression of components of TGF-beta signalling (TGF-beta1, TGF-beta receptors type 1 and 2, Smad 3 and 4) in tumour and associated stroma. Further we analyzed correlation to histological and clinical parameters (histological grade of differentiation (low-grade (i.e. grade 1 and 2) vs. high-grade (i.e. grade 3 and 4)), lymph node metastasis, distant metastasis, 5 year cancer related survival) using Chi-square or Fisher's exact test, when appropriate, to compare frequencies, Kaplan-Meier method to calculate 5-year rates of distant metastases and cancer-related survival and log rank test to compare the rates of distant metastases and survival. To identify independent prognostic factors Cox regression analysis including lymph node status and grading was performed. High-grade tumours and those with lymph node metastases showed higher rates of TAMs and lower expression of TGF-beta1. Loss of nuclear Smad4 expression in tumor was associated with presence of lymph node metastasis, but no influence on prognosis could be demonstrated. Decrease of both TGF-beta receptors in tumour-associated stroma was associated with increased lymph node metastasis and shorter survival. Stromal TGF-beta receptor 2

  5. Sporadic lymphoplasmacytic cholecystitis: a clinicopathologic entity.

    Science.gov (United States)

    Hammer, Suntrea T G; Appelman, Henry D

    2014-08-01

    To describe a sporadic form of lymphoplasmacytic cholecystitis (LPC), a condition known to occur in patients with chronic biliary tract disease. One year's worth of cholecystectomies was reviewed for sporadic cases of LPC. Histologic, radiologic, and clinical findings were reviewed and compared with noninflamed controls. Sporadic cases were also compared histologically with obstructive LPC cases. Sporadic LPC made up 7% of cholecystectomies, had a male predominance (54.2%), and more often presented with clinical signs of acute inflammation compared with controls. Radiologic findings identified gallstones in 71.4% of patients. The second most common finding was unexplained extrahepatic biliary dilation. There were no unique histologic findings to separate sporadic cases from those associated with pancreatobiliary disease. While obstructive LPC is traditionally described as acalculous, chronic cholecystitis, we show this inflammatory pattern occurs both in the presence of gallstones and outside of previously described disease categories. In addition, LPC occurs in a unique patient demographic (older men), often presenting similarly to acute cholecystitis. Copyright© by the American Society for Clinical Pathology.

  6. Colonic Diseases

    Science.gov (United States)

    ... Ulcerative colitis - ulcers of the colon and rectum Diverticulitis - inflammation or infection of pouches in the colon Irritable bowel syndrome - an uncomfortable condition causing abdominal cramping and other symptoms Treatment for colonic diseases varies greatly depending on the disease and its ...

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

    OpenAIRE

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

    2016-01-01

    Probiotic microorganisms such as lactic acid bacteria (LAB) exert a number of strain-specific health-promoting activities attributed to their immunomodulatory, anti-inflammatory and anti-carcinogenic properties. Despite recent attention, our understanding of the biological processes involved in the beneficial effects of LAB strains is still limited. To this end, the present study investigated the growth-inhibitory effects of Lactobacillus casei ATCC 393 against experimental colon cancer. Admi...

  8. Correlation between expression of major histocompatibility complex class I and that of antigen presenting machineries in carcinoma cell lines of the pancreas, biliary tract and colon

    OpenAIRE

    Imanishi, Tatsuya; Kamigaki, Takashi; Nakamura, Tetsu; Hayashi, Shun; Yasuda, Takashi; Kawasaki, Kentaro; Takase, Shiro; Ajiki, Tetsuo; Kuroda, Yoshikazu

    2006-01-01

    To elicit a tumor immune response, tumor antigens represented by majorhistocompatibility (MHC) class I complex on the cell surface is indispensable. Someinvestigators demonstrated that many cancer cells reduce expression ofβ2-microglobulin, a transporter of antigen presenting (TAP) or low molecular protein(LMP), due to the deletion mutant or point mutation. We investigated gene expressionlevels of antigen presenting machineries in 13 cell lines of the pancreas, biliary tractand colon cancer b...

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

    African Journals Online (AJOL)

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

  10. Molecular pathogenesis of serous Fallopian tube and ovarian carcinoma

    NARCIS (Netherlands)

    Nowee, M.E.

    2009-01-01

    Serous type Fallopian tube carcinoma (FTC) and ovarian carcinoma (OVCA) are gynaecological malignancies with a poor prognosis. Although most of the encountered tumours are sporadic, a positive family history is an important risk factor. Both tumour types have been linked to mutations in the BRCA1

  11. Medullary carcinoma of the thyroid - an unusual case of hyalinizing ...

    African Journals Online (AJOL)

    Medullary thyroid carcinoma is a neoplasm occurring in sporadic and familial patterns. A rare variant of medullary thyroid carcinoma shows microscopic features similar to hyalinizing trabecular adenoma of thyroid. Detection of this variant requires a high index of suspicion and immunohistochemical confirmation by ...

  12. Genetic instability in inherited and sporadic leukemias.

    Science.gov (United States)

    Popp, Henning D; Bohlander, Stefan K

    2010-12-01

    Genetic instability due to increased DNA damage and altered DNA repair is of central significance in the initiation and progression of inherited and sporadic human leukemias. Although very rare, some inherited DNA repair insufficiency syndromes (e.g., Fanconi anemia, Bloom's syndrome) have added substantially to our understanding of crucial mechanisms of leukemogenesis in recent years. Conversely, sporadic leukemias account for the main proportion of leukemias and here DNA damaging reactive oxygen species (ROS) play a central role. Although the exact mechanisms of increased ROS production remain largely unknown and no single pathway has been detected thus far, some oncogenic proteins (e.g., the activated tyrosine kinases BCR-ABL1 and FLT3-ITD) seem to play a key role in driving genetic instability by increased ROS generation which influences the disease course (e.g., blast crisis in chronic myeloid leukemia or relapse in FLT3-ITD positive acute myeloid leukemia). Of course other mechanisms, which promote genetic instability in leukemia also exist. A newly emerging mechanism is the genome-wide alteration of epigenetic marks (e.g., hypomethylation of histone H3K79), which promotes chromosomal instability. Taken together genetic instability plays a critical role both in inherited and sporadic leukemias and emerges as a common theme in both inherited and sporadic leukemias. Beyond its theoretical impact, the analysis of genetic instability may lead the way to the development of innovative therapy strategies. © 2010 Wiley-Liss, Inc.

  13. Annexin A10 expression correlates with serrated pathway features in colorectal carcinoma with microsatellite instability.

    Science.gov (United States)

    Kim, Jung Ho; Rhee, Ye-Young; Kim, Kyung-Ju; Cho, Nam-Yun; Lee, Hye Seung; Kang, Gyeong Hoon

    2014-12-01

    Annexin A10 (ANXA10) has recently been identified as a marker of sessile serrated adenomas/polyps of the colorectum. Although the serrated neoplasia pathway is thought to be involved in the majority of microsatellite instability-high (MSI-H) sporadic colorectal carcinomas (CRCs), the clinicopathological implications of ANXA10 expression in CRC are unknown. Here, we evaluated ANXA10 expression status in 168 MSI-H CRCs by immunohistochemistry. Among 168 MSI-H CRCs, nuclear staining for ANXA10 in tumor cells revealed 28 cases (17%) with ANXA10-positive (ANXA10+) tumors. Most of the ANXA10+ tumors were located in the proximal colon (96%, p < 0.001). The ANXA10+ phenotype in MSI-H CRC was significantly associated with female gender (68%, p = 0.016), CpG island methylator phenotype-high (CIMP-H) (68%, p < 0.001), MLH1 promoter hypermethylation (61%, p < 0.001), loss of MLH1 expression (82%, p = 0.019), and wild-type KRAS status (96%, p = 0.023). Survival analysis revealed no prognostic significance of ANXA10 expression in MSI-H CRC. In conclusion, ANXA10+ MSI-H colon carcinomas are characterized by serrated pathway features, including proximal location, female predominance, and high frequencies of CIMP-H status and MLH1 methylation. © 2014 APMIS. Published by John Wiley & Sons Ltd.

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

    DEFF Research Database (Denmark)

    Klarskov, Louise; Bernstein, Inge; Holck, Susanne

    2008-01-01

    Signet-ring cell carcinoma (SRCC) developing in the colorectum (CR) is infrequently identified at an early stage (no deeper than submucosa). Most such examples involve the submucosa. Merely 13 cases of intramucosal CR SRCC are at hand. We recently had the opportunity to study a specimen with two...... featured alterations in this complex with loss of membranous expression of both proteins and a shift with nuclear accumulation of beta-catenin, suggesting a disruption of the Wingless signaling pathway taking place at the transition from the intramucosal to the submucosal level....

  15. Colorectal carcinomas in MUTYH-associated polyposis display histopathological similarities to microsatellite unstable carcinomas

    International Nuclear Information System (INIS)

    Nielsen, Maartje; Hes, Frederik J; Morreau, Hans; Miranda, Noel FCC de; Puijenbroek, Marjo van; Jordanova, Ekaterina S; Middeldorp, Anneke; Wezel, Tom van; Eijk, Ronald van; Tops, Carli MJ; Vasen, Hans FA

    2009-01-01

    MUTYH-associated polyposis (MAP) is a recessively inherited disorder which predisposes biallelic carriers for a high risk of polyposis and colorectal carcinoma (CRC). Since about one third of the biallelic MAP patients in population based CRC series has no adenomas, this study aimed to identify specific clinicopathological characteristics of MAP CRCs and compare these with reported data on sporadic and Lynch CRCs. From 44 MAP patients who developed ≥ 1 CRCs, 42 of 58 tumours were analyzed histologically and 35 immunohistochemically for p53 and beta-catenin. Cell densities of CD3, CD8, CD57, and granzyme B positive lymphocytes were determined. KRAS2, the mutation cluster region (MCR) of APC, p53, and SMAD4 were analyzed for somatic mutations. MAP CRCs frequently localized to the proximal colon (69%, 40/58), were mucinous in 21% (9/42), and had a conspicuous Crohn's like infiltrate reaction in 33% (13/40); all of these parameters occurred at a higher rate than reported for sporadic CRCs. Tumour infiltrating lymphocytes (TILs) were also highly prevalent in MAP CRCs. Somatic APC MCR mutations occurred in 14% (5/36) while 64% (23/36) had KRAS2 mutations (22/23 c.34G>T). G>T tranversions were found in p53 and SMAD4, although the relative frequency compared to other mutations was low. MAP CRCs show some similarities to micro-satellite unstable cancers, with a preferential proximal location, a high rate of mucinous histotype and increased presence of TILs. These features should direct the practicing pathologist towards a MAP aetiology of CRC as an alternative for a mismatch repair deficient cause. High frequent G>T transversions in APC and KRAS2 (mutated in early tumour development) but not in P53 and SMAD4 (implicated in tumour progression) might indicate a predominant MUTYH effect in early carcinogenesis

  16. Sporadic early-onset colorectal cancer is a specific sub-type of cancer: a morphological, molecular and genetics study.

    Directory of Open Access Journals (Sweden)

    Sylvain Kirzin

    Full Text Available Sporadic early onset colorectal carcinoma (EOCRC which has by definition no identified hereditary predisposition is a growing problem that remains poorly understood. Molecular analysis could improve identification of distinct sub-types of colorectal cancers (CRC with therapeutic implications and thus can help establish that sporadic EOCRC is a distinct entity. From 954 patients resected for CRC at our institution, 98 patients were selected. Patients aged 45-60 years were excluded to help define "young" and "old" groups. Thirty-nine cases of sporadic EOCRC (patients ≤ 45 years with microsatellite stable tumors were compared to both microsatellite stable tumors from older patients (36 cases, patients>60 years and to groups of patients with microsatellite instability. Each group was tested for TP53, KRAS, BRAF, PIK3CA mutations and the presence of a methylator phenotype. Gene expression profiles were also used for pathway analysis. Compared to microsatellite stable CRC from old patients, sporadic EOCRC were characterized by distal location, frequent synchronous metastases and infrequent synchronous adenomas but did not have specific morphological characteristics. A familial history of CRC was more common in sporadic EOCRC patients despite a lack of identified hereditary conditions (p = 0.013. Genetic studies also showed the absence of BRAF mutations (p = 0.022 and the methylator phenotype (p = 0.005 in sporadic EOCRC compared to older patients. Gene expression analysis implicated key pathways such as Wnt/beta catenin, MAP Kinase, growth factor signaling (EGFR, HGF, PDGF and the TNFR1 pathway in sporadic EOCRC. Wnt/beta catenin signaling activation was confirmed by aberrant nuclear beta catenin immunostaining (p = 0.01. This study strongly suggests that sporadic EOCRC is a distinct clinico-molecular entity presenting as a distal and aggressive disease associated with chromosome instability. Furthermore, several signaling pathways including the

  17. Sequential radioimmunotherapy with 177Lu- and 211At-labeled monoclonal antibody BR96 in a syngeneic rat colon carcinoma model

    DEFF Research Database (Denmark)

    Eriksson, Sophie E; Elgström, Erika; Bäck, Tom

    2014-01-01

    for small, established tumors. A combination of such radionuclides may be successful in regimens of radioimmunotherapy. In this study, rats were treated by sequential administration of first a 177Lu-labeled antibody, followed by a 211At-labeled antibody 25 days later. METHODS: Rats bearing solid colon....... The rats suffered from reversible myelotoxicity after treatment. CONCLUSIONS: Sequential administration of 177Lu-BR96 and 211At-BR96 resulted in tolerable toxicity providing halogen blocking but did not enhance the therapeutic effect....

  18. Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome).

    Science.gov (United States)

    Bresler, Scott C; Padwa, Bonnie L; Granter, Scott R

    2016-06-01

    Nevoid basal cell carcinoma syndrome, or basal cell nevus syndrome (Gorlin syndrome), is a rare autosomal dominantly inherited disorder that is characterized by development of basal cell carcinomas from a young age. Other distinguishing clinical features are seen in a majority of patients, and include keratocystic odontogenic tumors (formerly odontogenic keratocysts) as well as dyskeratotic palmar and plantar pitting. A range of skeletal and other developmental abnormalities are also often seen. The disorder is caused by defects in hedgehog signaling which result in constitutive pathway activity and tumor cell proliferation. As sporadic basal cell carcinomas also commonly harbor hedgehog pathway aberrations, therapeutic agents targeting key signaling constituents have been developed and tested against advanced sporadically occurring tumors or syndromic disease, leading in 2013 to FDA approval of the first hedgehog pathway-targeted small molecule, vismodegib. The elucidation of the molecular pathogenesis of nevoid basal cell carcinoma syndrome has resulted in further understanding of the most common human malignancy.

  19. Outcome of colonic surgery in elderly patients with colon cancer.

    Science.gov (United States)

    Hermans, E; van Schaik, P M; Prins, H A; Ernst, M F; Dautzenberg, P J L; Bosscha, K

    2010-01-01

    Introduction. Colonic cancer is one of the most commonly diagnosed malignancies and most often occurs in patients aged 65 years or older. Aim. To evaluate the outcome of colonic surgery in the elderly in our hospital and to compare five-year survival rates between the younger and elderly patients. Methods. 207 consecutive patients underwent surgery for colon cancer. Patients were separated in patients younger than 75 and older than 75 years. Results. Elderly patients presented significantly more (P younger group was 62% compared with 36% in the elderly (P younger patients compared with 32% in the elderly (P < .05). Conclusion. Curative resection of colonic carcinoma in the elderly is well tolerated and age alone should not be an indication for less aggressive therapy. However, the type and number of co-morbidities influence post-operative mortality and morbidity.

  20. Analysis of APC allelic imbalance/loss of heterozygosity and APC protein expression in cutaneous squamous cell carcinomas.

    LENUS (Irish Health Repository)

    Gray, Sarah E

    2012-02-01

    BACKGROUND: The adenomatous polyposis coli (APC) gene is a tumor suppressor gene which is mutated in the hereditary disease, familial adenomatous polyposis (FAP). Somatic mutations of the APC gene have also been identified in the majority of sporadic colorectal carcinomas, and mutation of the APC gene appears to be an early step in the initiation of colon cancer. Loss of heterozygosity (LOH) of APC has been described in a variety of other cancer types, including renal cell carcinoma, gastric cancer, non-small cell lung cancer, endometrial cancer and oral squamous cell carcinomas (SCC). AIM: To determine the role played by APC gene in the genesis of cutaneous SCC. MATERIALS AND METHODS: Allelic imbalance\\/loss of heterozygosity (AI\\/LOH) was examined in twenty-two histologically confirmed cutaneous squamous cell carcinomas (SCC) using microsatellite markers, proximal to the APC gene. Immunohistochemical analysis of APC protein expression was also examined in the cutaneous SCC. RESULTS: AI\\/LOH was detected in 60% of the SCC samples using D5S346 marker (proximal to the APC gene). Ninty-five percent of the SCC samples showed positive reduced APC expression, however the localization of the APC protein was abnormal. CONCLUSION: The abnormal expression of APC suggests that APC gene may play a role in cutaneous SCC development.

  1. A collaborative study of a test for carcinoembryonic antigen (CEA) in the sera of patients with carcinoma of the colon and rectum

    Science.gov (United States)

    1972-01-01

    Five university centres in Canada and the United States have collaborated in a study of a test for carcinoembryonic antigen, with the Montreal General Hospital laboratory acting as the reference laboratory, examining duplicate halves of specimens from patients examined in local laboratories. Between June 1971 and April 1972, 503 patients were admitted to the study, 146 with cancer of the colon or rectum. Discrimination between colo-rectal cancer and “other” diagnoses was good at 2.5 ng./ml. or more, such a result being obtained in 66% of the patients with colo-rectal cancer in the local laboratories and 62% in the reference laboratory compared with 39% and 33% respectively of patients with “other” diagnoses. Patients with Duke's C lesions of the colon or rectum were more likely to have raised CEA levels than patients with more localized lesions. CEA was also more commonly found in patients with other cancers and in patients with liver disease than in patients with other (benign) diagnoses. It is concluded that the test can be reproduced in other laboratories and that it or another simplified technique could become an important diagnostic aid for colo-rectal cancer. PMID:5042884

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

    Directory of Open Access Journals (Sweden)

    A. Acosta Arencibia

    2010-12-01

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

  3. Mismatch repair genes expression defects & association with clinicopathological characteristics in colorectal carcinoma.

    Science.gov (United States)

    Kaur, Gurjeet; Masoud, Abdelhafid; Raihan, N; Radzi, M; Khamizar, W; Kam, Lee Suk

    2011-08-01

    DNA mismatch repair gene (MMR) abnormalities are seen in 95 per cent of hereditary nonpolyposis colorectal cancer (HNPCC) and 10-15 per cent of sporadic colorectal cancers. There are no data on MMR abnormalities in Malaysian colorectal cancer patients. This study was aimed to determine the frequency of abnormal MMR gene protein expression in colorectal carcinoma in Northern Peninsular Malaysia using immunohistochemistry. Clinicopathological information was obtained from 148 patients' records who underwent bowel resection for colorectal cancer (CRC) at the three hospitals in Malaysia. Immunohistochemistry for MLH1, MSH2, MSH6 and PMS2 proteins were performed on paraffin embedded tissue containing carcinoma. A total of 148 subjects and 150 colorectal carcinomas of sporadic and hereditary types were assessed. Three patients had synchronous tumours. Twenty eight cancers (18.6%) from 26 subjects (17.6%) had absent immunohistochemical expression of any one of the MMR gene proteins. This comprised absent MLH1 only - 3 cancers, absent MSH2 only - 3, absent MSH6 only - 2, absent PMS2 only - 3, absent MLH1 and PMS2 - 14, absent MSH2 and MSH6 - 2 and absent MLH1, MSH6 and PMS2 - 1. There was significant association between abnormal MMR gene protein expression and proximal colon cancers, mucinous, signet ring and poorly differentiated morphology. Cancers with abnormal MMR gene expression were associated with microsatellite instability-high (MSI-H) phenotype. About 15 per cent demonstrated absent MSH2, MSH6 and PMS2 protein expression in isolation or in combination with other MMR genes, which often predicts a germline mutation, synonymous with a diagnosis of HNPCC. This appears to be high frequency compared to reported data.

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

    Directory of Open Access Journals (Sweden)

    Rubén Valle

    2009-09-01

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

  5. Inhibition of p70S6K1 Activation by Pdcd4 Overcomes the Resistance to an IGF-1R/IR Inhibitor in Colon Carcinoma Cells.

    Science.gov (United States)

    Zhang, Yan; Wang, Qing; Chen, Li; Yang, Hsin-Sheng

    2015-03-01

    Agents targeting insulin-like growth factor 1 receptor (IGF-1R) are being actively examined in clinical trials. Although there has been some initial success of single-agent targeting IGF-1R, attempts in later studies failed because of resistance. This study aimed to understand the effects of programmed cell death 4 (Pdcd4) on the chemosensitivity of the IGF-1R inhibitor OSI-906 in colorectal cancer cells and the mechanism underlying this impact. Using OSI-906-resistant and -sensitive colorectal cancer cells, we found that the Pdcd4 level directly correlates with cell chemosensitivity to OSI-906. In addition, tumors derived from Pdcd4 knockdown cells resist the growth inhibitory effect of OSI-906 in a colorectal cancer xenograft mouse model. Moreover, Pdcd4 enhances the antiproliferative effect of OSI-906 in resistant cells through suppression of p70S6K1 activation. Knockdown of p70S6K1, but not p70S6K2, significantly increases the chemosensitivity of OSI-906 in cultured colorectal cancer cells. Furthermore, the combination of OSI-906 and PF-4708671, a p70S6K1 inhibitor, efficiently suppresses the growth of OSI-906-resistant colon tumor cells in vitro and in vivo. Taken together, activation of p70S6K1 that is inhibited by Pdcd4 is essential for resistance to the IGF-1R inhibitor in colon tumor cells, and the combinational treatment of OSI-906 and PF-4708671 results in enhanced antiproliferation effects in colorectal cancer cells in vitro and in vivo, providing a novel venue to overcome the resistance to the IGF-1R inhibitor in treating colorectal cancer. ©2015 American Association for Cancer Research.

  6. Iodine-131-labeled MAb F(ab')2 fragments are more efficient and less toxic than intact anti-CEA antibodies in radioimmunotherapy of large human colon carcinoma grafted in nude mice

    International Nuclear Information System (INIS)

    Buchegger, F.; Pelegrin, A.; Delaloye, B.; Bischof-Delaloye, A.; Mach, J.P.

    1990-01-01

    During one week, beginning 18 days after transplantation, nude mice bearing human colon carcinoma ranging from 115 to 943 mm3 (mean 335 mm3) were treated by repeated intravenous injections of either iodine-131-( 131 I) labeled intact antibodies or 131 I-labeled corresponding F(ab')2 fragments of a pool of four monoclonal antibodies (MAbs) directed against distinct epitopes of carcinoembryonic antigen (CEA). Complete tumor remission was observed in 8 of 10 mice after therapy with F(ab')2 and 6 of the animals survived 10 mo in good health. In contrast, after treatment with intact MAbs, tumors relapsed in 7 of 8 mice after remission periods of 1 to 3.5 mo despite the fact that body weight loss and depression of peripheral white blood cells, symptoms of radiation toxicity, and the calculated radiation doses for liver, spleen, bone, and blood were increased or equal in these animals as compared to mice treated with F(ab')2

  7. The driver landscape of sporadic chordoma.

    Science.gov (United States)

    Tarpey, Patrick S; Behjati, Sam; Young, Matthew D; Martincorena, Inigo; Alexandrov, Ludmil B; Farndon, Sarah J; Guzzo, Charlotte; Hardy, Claire; Latimer, Calli; Butler, Adam P; Teague, Jon W; Shlien, Adam; Futreal, P Andrew; Shah, Sohrab; Bashashati, Ali; Jamshidi, Farzad; Nielsen, Torsten O; Huntsman, David; Baumhoer, Daniel; Brandner, Sebastian; Wunder, Jay; Dickson, Brendan; Cogswell, Patricia; Sommer, Josh; Phillips, Joanna J; Amary, M Fernanda; Tirabosco, Roberto; Pillay, Nischalan; Yip, Stephen; Stratton, Michael R; Flanagan, Adrienne M; Campbell, Peter J

    2017-10-12

    Chordoma is a malignant, often incurable bone tumour showing notochordal differentiation. Here, we defined the somatic driver landscape of 104 cases of sporadic chordoma. We reveal somatic duplications of the notochordal transcription factor brachyury (T) in up to 27% of cases. These variants recapitulate the rearrangement architecture of the pathogenic germline duplications of T that underlie familial chordoma. In addition, we find potentially clinically actionable PI3K signalling mutations in 16% of cases. Intriguingly, one of the most frequently altered genes, mutated exclusively by inactivating mutation, was LYST (10%), which may represent a novel cancer gene in chordoma.Chordoma is a rare often incurable malignant bone tumour. Here, the authors investigate driver mutations of sporadic chordoma in 104 cases, revealing duplications in notochordal transcription factor brachyury (T), PI3K signalling mutations, and mutations in LYST, a potential novel cancer gene in chordoma.

  8. Colonic angiodysplasia

    Energy Technology Data Exchange (ETDEWEB)

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

    1984-11-01

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

  9. Colonic angiodysplasia

    International Nuclear Information System (INIS)

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

    1984-01-01

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

  10. Colonic locomotion

    NARCIS (Netherlands)

    Dodou, D.

    2006-01-01

    The most effective screening method for colonic cancer is colonoscopy. However, colonoscopy cannot be easily embraced by the population because of the related pain intensity. Robotic devices that pull themselves forward through the colon are a possible alternative. The main challenge for such

  11. Colonic lipoma

    International Nuclear Information System (INIS)

    Siddiqui, M.S.; Khatri, A.R.; Quraishy, M.S.; Fatima, L.; Muzaffar, S.

    2003-01-01

    Lipoma of the colon is rare and may lead to intestinal obstruct. We have presented two cases of colonic lipoma. Both were elderly females, one presented with diarrhea and the other with sub-acute intestinal obstruction. After colonoscopy surgical removal was done. Histopathology revealed lipoma. (author)

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

    Directory of Open Access Journals (Sweden)

    Gustavo Costa Verardino

    2011-06-01

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

  13. MTHFR polymorphisms as prognostic factors in sporadic colorectal cancer.

    Science.gov (United States)

    Osian, Gelu; Procopciuc, Lucia; Vlad, Liviu

    2007-09-01

    Theoretically, individuals having at least one mutant allele present a modified activity of the MTHFR enzyme and low methylation, DNA synthesis-repair respectively, which could imply a higher risk of colorectal cancer. The purpose of this study was to investigate the relations of these mutations with the clinico-pathological aspects of colorectal cancer. The study included 69 patients with sporadic colorectal cancer. The relative risk in homozygous patients with a normal allele and for mutations C667T and A1298C, in heterozygous patients with one normal and one mutant allele, and for homozygous patients for the mutant allele was calculated. C667T and A1298C mutations represent a risk factor for colorectal cancer with an OR (odds ratio) = 2.13 (CI (0.51-8.91)) and 3 (CI(0.3-29.58), respectively, in homozygous patients. These mutations are associated with a more frequent location of lesions at the colon level, OR=2.3 and 2.15 respectively. The incidence of the A1298C mutation was more frequent in stage N0 than N+ (p<0.05), pT2 vs. pT3 (p<0.05), as well as in Dukes stages B and D vs. A or C (p<0.05). The results obtained support the hypothesis of an increased colorectal cancer prevalence in patients with one of the MTHFR gene mutations. These patients develop colon cancer more frequently, they present lymph node invasion more rarely, and develop more often distant metastases.

  14. Secondary neoplasms of the larynx from a colonic adenocarcinoma

    DEFF Research Database (Denmark)

    Dadkhah, Naser; Hahn, Christoffer

    2015-01-01

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

  15. Laparoscopic sentinel lymph node identification in patients with colon carcinoma using a near-infrared dye: description of a new technique and feasibility study.

    Science.gov (United States)

    van der Pas, Martijn H G M; Ankersmit, Marjolein; Stockmann, Hein B A C; Silvis, Rob; van Grieken, Nicole C T; Bril, Herman; Meijerink, Wilhelmus J H J

    2013-04-01

    After promising results were obtained from studies in large animals, a technique using indocyanine green (ICG) is being introduced for sentinel lymph node (SLN) biopsy in colon cancer patients. Colon cancer patients without clinical signs of metastatic disease, presenting at the VU University Medical Center (Amsterdam, The Netherlands) or Kennemer Gasthuis (Haarlem, The Netherlands), were asked to participate in the study. During laparoscopy, a subserosal injection of 2.5 mg of ICG diluted in 1 mL of 0.9% NaCl plus 2% human albumin was performed using a percutaneously inserted long rigid or flexible needle. After injection, a near-infrared laparoscope (Olympus Corp., Tokyo, Japan) was used for lymph flow and SLN visualization. The SLNs were laparoscopically harvested and analyzed by a senior pathologist using multisectioning and immunohistochemistry. Fourteen patients were included (six women, eight men), with a median age of 75.5 (interquartile range [IQR], 67.8-81.0) years and a median body mass index of 25.1 (IQR, 22.7-26.0) kg/m(2). Median tumor diameter was 4.5 (IQR, 3.4-7.0) cm. At least one SLN was identified in all patients, with a median number of 2.0 (IQR, 2.0-3.3) SLNs. The median time between injection and identification of the SLN was 15.0 (IQR, 13.3-29.3) minutes. Positioning of the needle tip into the subserosal layer was found to be more effective using the flexible needle. When this flexible needle was used, less spill of dye was observed. All SLNs were negative. We observed four false-negative nodes, all after using a rigid needle. None of the patients showed an adverse reaction to the ICG injection. Preliminary results of laparoscopic sentinel node identification using a near-infrared dye show this procedure is safe and feasible. It was possible to detect lymph nodes in all patients. Large tumor size, drainage to adjacent lymphatic vessels, and the use of a rigid needle might contribute to false-negative nodes.

  16. Comparison Between Sporadic and Misdiagnosed Sporadic Creutzfeldt-Jakob Disease: A Report of Two Cases.

    Science.gov (United States)

    Zhao, Xiongfei; Yu, Yingxin; Zhao, Zhiru; Xu, Jiaping

    2015-06-01

    Definite accurate diagnosis for Creutzfeldt-Jakob disease (CJD) depends on neuropathologic examination of brain biopsy or autopsy. However, transmissible nature makes the invasive examination dangerous. This study was set to determine that the clinical features are for the diagnosis of CJD through a comparison study. We compared clinical features of two cases with initial diagnosis of sporadic CJD. One case was finally diagnosed as definite sporadic CJD. According to World Health Organization diagnosis criteria, the other one, which had been diagnosed as probable sporadic CJD, was confirmed as limbic encephalitis after long-term follow-up. Compared with the case of definite sporadic CJD, the misdiagnosed case did not present typical electroencephalogram (EEG) and diffusion-weighted in magnetic resonance images (DWI) of CJD. However, cerebrospinal fluid in the misdiagnosed patient showed 14-3-3 protein positivity. The patient conditions improved after treatment. Through this case comparison, we conclude that EEG and DWI are necessary for accurate diagnosis of sporadic CJD. Further, long-term follow-up is crucial to diagnosis and treatment of CJD.

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

    Directory of Open Access Journals (Sweden)

    Piotr Czapiewski

    2016-11-01

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

  18. Comparative evaluation of curcumin and curcumin loaded- dendrosome nanoparticle effects on the viability of SW480 colon carcinoma and Huh7 hepatoma cells

    Directory of Open Access Journals (Sweden)

    M.J. Dehghan Esmatabadi

    2015-06-01

    Full Text Available Background and objectives: Colorectal cancer is the third most common cancer and a major cause of morbidity globally. Hepatocellular carcinoma is a leading cause of death in the world. About 80% of all anticancer drugs are somehow related to natural products. One of the most important of these natural compounds is curcumin, the main component of turmeric that has a wide range of pharmacological activities. Curcumin has been found to suppress cell proliferation and decrease cell viability in various types of cancer cells; however, owing to lack of aqueous solubility, curcumin has shown reduced bioavailability in studies. Recent studies have shown that new 400th generation of dendrosome nanoparticle can increase bioavailability of curcumin and thus enhance the cytotoxic properties.  The aim of this study was to determine effectiveness of curcumin alone and in combination with 400th generation dendrosome nanoparticles (DNC on cell viability rate in SW480 and Huh7 cells. Methods: SW480 and Huh7 cells were incubated with different concentrations of curcumin and DNC (0-50μM for 24, 48 and 72 h. Then cytotoxicity was assessed by MTT assay and IC50 was determined. Results: The results suggested that the concentration-dependent inhibitory effect of DNC was stronger than curcumin on SW480 and Huh7 cells. Conclusion: The results suggest DNC as a more effective herbal anticancer agent for colorectal and hepatocellular tumors.

  19. Cell proliferation and ageing in mouse colon

    International Nuclear Information System (INIS)

    Hamilton, E.; Franks, L.M.

    1980-01-01

    Cell kinetic parameters in the descending colon of unirradiated mice, 3-30-months-old were compared with those in mice irradiated repeatedly from the age of 6 or 24 months. The latter animals were given 1250 rad local X-irradiation to the colon every 6 weeks. Dose-survival curves showed the colon crypts of 6 and 24-months-old mice were similarly radiosensitive. In unirradiated mice the number of crypts per colon section decreased significantly at 30 months, but no significant age-related changes were seen in crypt size or labelling index (LI). Cell proliferation returned to control levels within 6 weeks of each X-ray dose and remained at this level for 20 weeks after the final dose. Later, cell proliferation in the irradiated colon fell significantly below control. A total of 6 or 7 doses each of 1250 rad produced only 1 colon carcinoma amongst 50 mice kept until they died. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2005-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Chung-Weng Phang

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

  2. CPP2-p16MIS treatment–induced colon carcinoma cell death in vitro and prolonged lifespan of tumor-bearing mice

    International Nuclear Information System (INIS)

    Wang, Lifeng; Chen, Haijin; Yu, Jinlong; Lin, Xiaohua; Qi, Jia; Cui, Chunhui; Xie, Lang; Huang, Shuxin

    2016-01-01

    Cell-penetrating peptides (CPPs) are a research hotspot due to their noninvasive delivery ability. Among the identified CPPs, the TAT and R8 peptides have been preferentially applied to transduction into different cells. However, this process is nonselective among various cells. Recent research suggested that CPP2 could selectively penetrate human colorectal cancer (CRC) cells. Using in vitro experiments, the mean fluorescence intensity of fluorescein isothiocyanate–labeled CPPs (CPPs-FITC) incubated with different cell lines was compared to corroborate the colon tumor targeting ability of CPP2. The targeting ability of CPP2 was determined in the same way in tumor-bearing mice. We synthesized antitumor peptides by fusing CPP2 to the minimal inhibitory sequence of p16 (p16MIS), which had the ability to restore the function of lost p16, the expression of which was absent in tumor cell lines of various origins. The antitumor effect of the combined peptide was tested in both CRC cell lines and tumor-bearing mice. In each CRC cell line, the mean fluorescence intensity of CPP2-FITC was higher than that of the TAT-FITC (p < 0.001) and R8-FITC (p < 0.001) groups. CPP2-p16MIS, the targeting carrier, showed a higher antitumor response in the in vitro cell research. CPP2-p16MIS showed a prolonged mean lifespan of tumor-bearing mice, further characterizing its role in specific tumor-targeting ability in vivo. Survival analysis showed that the mice treated with CPP2-p16MIS had significantly longer survival than the mice treated with phosphate-buffered saline (p < 0.05) or those treated with control peptides, including the CPP2 (p < 0.05) and p16MIS (p < 0.05) groups. CPP2 could more selectively penetrate CRC cells than TAT or R8 as well as effectively deliver the p16MIS to the tumor

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

    African Journals Online (AJOL)

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

  4. Sporadic colorectal cancer: Studying ways to an end

    Science.gov (United States)

    Fidalgo, Paulo; Filipe, Bruno; Albuquerque, Cristina; Fonseca, Ricardo; Chaves, Paula; Pereira, António D

    2015-01-01

    Introduction Although colorectal cancer (CRC) has often been regarded as a single entity, different pathways may lead to macroscopically similar cancers. These pathways may evolve into a patchy colonic field defect that we aimed to study in consecutive CRC patients. Methods In a single-center, observational, prospective study, consecutive CRC patients were included if surgery and a perioperative colonoscopy were planned. Personal and familial history data were collected. Tumors were studied for microsatellite instability (MSI) status, DNA repair protein expression (DRPE) and presence of BRAF and/or APC mutations. Macroscopically normal mucosa samples were tested for APC mutations. Presence and location of synchronous and metachronous adenomas and patient follow-up were analyzed. The association of two categorical variables was tested through the Fisher’s exact test (SPSS 19). Results Twenty-four patients (12 male, mean age 69 years) were studied. High-grade MSI (MSI-H) was found in eight tumors—these were significantly more common in the right colon (p = 0.047) and more likely to have an altered DRPE (p = 0.007). BRAF mutation was found in two of six tested MSI-H tumors. APC gene mutations were found in nine of 16 non-MSI-H tumors and absent in normal mucosa samples. There was a nonsignificant co-localization of CRC and synchronous adenomas and a significant co-localization (p = 0.05) of synchronous and metachronous adenomas. Discussion Sporadic CRCs evolve through distinct pathways, evidenced only by pathological and molecular analysis, but clinically relevant both for patients and their families. In non-MSI-H tumors, the expected APC gene mutations were not detected by the most commonly used techniques in a high number of cases. More studies are needed to fully characterize these tumors and to search for common early events in normal mucosa patches, which might explain the indirect evidence found here for a field defect in the colon. PMID:27087959

  5. Colon neoplasm

    International Nuclear Information System (INIS)

    Kimura F, K.

    1991-01-01

    The main aspects of colon neoplasms are described, including several factors that predispose the disease, the occurrence, the main biomedical radiography and the evaluation after the surgery. (C.G.C.)

  6. Risk factors for sporadic ovarian cancer

    Directory of Open Access Journals (Sweden)

    M. M. Vysotsky

    2010-01-01

    Full Text Available The review of the literature on the problems of sporadic ovarian cancer details the present views of its disputable risk factors, such as dietary habits, body weight, contraception, and labor, and age of commencing a sexual activity. It discusses the dietary and sexual behavior model that has changed since the Neolithic, as well as the number of menses and ovulations throughout the reproductive peri- od. The works by authors dealing with the impact of smoking and alcohol consumption on the risk of ovarian cancer are analyzed.

  7. Early Detection of Sporadic Pancreatic Cancer

    Science.gov (United States)

    Kenner, Barbara J.; Chari, Suresh T.; Cleeter, Deborah F.; Go, Vay Liang W.

    2015-01-01

    Abstract Innovation leading to significant advances in research and subsequent translation to clinical practice is urgently necessary in early detection of sporadic pancreatic cancer. Addressing this need, the Early Detection of Sporadic Pancreatic Cancer Summit Conference was conducted by Kenner Family Research Fund in conjunction with the 2014 American Pancreatic Association and Japan Pancreas Society Meeting. International interdisciplinary scientific representatives engaged in strategic facilitated conversations based on distinct areas of inquiry: Case for Early Detection: Definitions, Detection, Survival, and Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies. Ideas generated from the summit have led to the development of a Strategic Map for Innovation built upon 3 components: formation of an international collaborative effort, design of an actionable strategic plan, and implementation of operational standards, research priorities, and first-phase initiatives. Through invested and committed efforts of leading researchers and institutions, philanthropic partners, government agencies, and supportive business entities, this endeavor will change the future of the field and consequently the survival rate of those diagnosed with pancreatic cancer. PMID:25938853

  8. [Microsatellite alterations on chromosome 9p21-22 in sporadic colorectal cancer].

    Science.gov (United States)

    Zhang, Y; Lai, M

    1999-12-01

    To study whether alteration of p16 plays an important role in the development of colorectal carcinomas and the relationship between the molecular changes of 9p21-22 chromosome subregion in sporadic colorectal cancers. To detect microsatellite instability (MSI) and loss of heterozygosity (LOH) by PCR, denatured-polyacrylamide gel-electrophoresis and silver staining (microsatellite DNA-PCR-silver staining method) and to compare the results with the clinopathological parameters. Between MSI positive and negative cases and the clinopathological findings, some evidences found in the MSI positive group were as follows: (1) tendency towards younger patients (usually < 50 years in age, P < 0.05); (2) more frequently seen in mucoid carcinomas (P < 0.01). Microsatellite DNA-PCR-silver staining method is very sensitive in detecting even a tiny change of a single base. MSI occured in the selected microsatellite loci of different subregions and different chromosomes might be different in significance, therefore, a right choice of the suitable loci for studying the microsatellite changes is important. Since the frequency of loss of heterozygosity at 9p21-22 is low (merely 8.42%), it is considered that p16 is not closely associated with the development of sporadic colorectal cancer.

  9. Absence of RET proto-oncogene abnormalities in sporadic parathyroid tumors

    Energy Technology Data Exchange (ETDEWEB)

    Pausova, Z.; Janicic, N.; Konrad, E. [McGill Univ. and Royal Victoria Hospital, Montreal (Canada)] [and others

    1994-09-01

    Parathyroid tumors can occur either sporadically or as a part of inherited cancer syndromes such as multiple endocrine neoplasia (MEN) type 2A. Recently, development of this syndrome has been shown to be related to specific mutations in the RET proto-oncogene, a putative receptor tyrosine kinase. Activation of this proto-oncogene has been demonstrated not only in tumors of the MEN 2A syndrome, but also in other neoplasia of neuroectoderm origin, namely papillary thyroid carcinoma where a rearrangement of the RET proto-oncogene has been found. In the present study, a role of the RET proto-oncogene in the development of sporadic parathyroid tumors was investigated by analyzing DNA samples obtained from 13 parathyroid adenomas and 6 parathyroid hyperplasias. Southern blot, using BamHI restricted DNA, did not reveal any gross alteration of the gene. Polymerase chain reaction (PCR) was then employed to amplify DNA fragments corresponding to exons 10 and 11 in which all MEN 2A mutations have been identified. Amplified DNA fragments were all of expected size (exon 10, 182 bp; exon 11, 233 bp). Since a single point mutation at codon 634 has been found to be associated in close to 90% of cases with development of parathyroid tumors in patients with the MEN 2A syndrome, exon 11, containing this codon, was further examined by direct sequence analysis. Sequences obtained from all tumors tested, however, did not differ from the wild type sequence. Therefore, the mutation of the RET proto-oncogene commonly associated with parathyroid neoplasias in MEN 2A is uncommon in sporadic parathyroid tumors. This suggests that the pathogenesis of parathyroid tumors occurring sporadically may be different from those occurring in patients with the MEN 2A syndrome.

  10. Tumour suppressor genes in sporadic epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Liu, Ying; Ganesan, Trivadi S

    2002-01-01

    Ovarian cancer is the most frequent cause of death from gynaecological malignancies in the western world, and sporadic epithelial ovarian cancer is its most predominant form. The aetiology of sporadic ovarian cancer remains unknown. Genetic studies have enabled a better understanding...... of the evolution of tumour progression. A major focus of research has been to identify tumour suppressor genes implicated in sporadic ovarian cancer over the past decade. Several tumour suppressor genes have been identified by strategies such as positional cloning and differential expression display. Further...... research is warranted to understand fully their contribution to the pathogenesis of sporadic ovarian cancer....

  11. Verrucous carcinoma at ileostomy site

    OpenAIRE

    Dhakre, Vijay; Nagral, Sanjay

    2017-01-01

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

  12. Immunological comparison of ovarian and colonic CEA

    International Nuclear Information System (INIS)

    Burtin, P.; Gendron, M.C.; Maunoury, M.T.; Lamerz, R.; Schnabel, G.

    1982-01-01

    Ovarian and colonic CEA were compared immunologically by means of antisera prepared against each of them. CEAs of both origins were found identical by immunodiffusion methods. In radioimmunological experiments, slight differences were observed between some but not all ovarian CEAs and colonic CEAs and also between different preparations of colonic CEA: no organ specificity of ovarian CEA could be demonstrated. Finally, CEA level was measured in 41 sera of patients with ovarian carcinoma by two radioimmunoassays, one using colonic CEA as tracer and standard and anti-colonic CEA serum, the other using ovarian CEA and anti-ovarian CEA serum: the values given by the two assays were highly correlated (rsub(s) = 0.8107), meaning that an organ specific assay for ovarian CEA is not needed. (Auth.)

  13. MRI of sporadic Creutzfeldt-Jakob disease

    International Nuclear Information System (INIS)

    Kong, A.; Vliet, A. Van der.

    2008-01-01

    Full text: The key MRI findings in five cases of sporadic Creutzfeldt-Jakob disease (CJD) are illustrated with four 'definite' and one 'probable' according to World Health Organization criteria. Close attention to fluid-attenuation inversion recovery and diffusion-weighted imaging sequences are important for diagnosis, noting especially restricted diffusion in cortical and deep grey matter. Our study and those of others show predominant cortical, caudate and thalamic involvement. This pattern is highly sensitive and specific for the diagnosis. Fluid-attenuation inversion recovery and diffusion-weighted imaging signal abnormality becomes progressively more extensive and bilateral as disease progresses, but may become less pronounced in end-stage disease because of atrophy.

  14. Endoskopisk mucosaresektion i colon og rectum

    DEFF Research Database (Denmark)

    Malmstrom, M.L.; Meisner, S.

    2008-01-01

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

  15. Muscarinic Receptor Signaling in Colon Cancer

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-03-02

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

  16. Muscarinic Receptor Signaling in Colon Cancer

    International Nuclear Information System (INIS)

    Rosenvinge, Erik C. von; Raufman, Jean-Pierre

    2011-01-01

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

  17. Muscarinic Receptor Signaling in Colon Cancer

    Directory of Open Access Journals (Sweden)

    Jean-Pierre Raufman

    2011-03-01

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

  18. Learning about Colon Cancer

    Science.gov (United States)

    ... What do we know about heredity and colon cancer? Colon cancer, a malignant tumor of the large intestine, ... page Additional Resources for Information on Hereditary Colon Cancer Colon and Rectal Cancer Information [cancer.gov] The most ...

  19. Sporadic aurorae observed in East Asia

    Directory of Open Access Journals (Sweden)

    D. M. Willis

    2007-03-01

    Full Text Available All the accessible auroral observations recorded in Chinese and Japanese histories during the interval AD 1840–1911 are investigated in detail. Most of these auroral records have never been translated into a Western language before. The East Asian auroral reports provide information on the date and approximate location of each auroral observation, together with limited scientific information on the characteristics of the auroral luminosity such as colour, duration, extent, position in the sky and approximate time of occurrence. The full translations of the original Chinese and Japanese auroral records are presented in an appendix, which contains bibliographic details of the various historical sources. (There are no known reliable Korean observations during this interval. A second appendix discusses a few implausible "auroral" records, which have been rejected. The salient scientific properties of all exactly dated and reliable East Asian auroral observations in the interval AD 1840–1911 are summarised succinctly. By comparing the relevant scientific information on exactly dated auroral observations with the lists of great geomagnetic storms compiled by the Royal Greenwich Observatory, and also the tabulated values of the Ak (Helsinki and aa (Greenwich and Melbourne magnetic indices, it is found that 5 of the great geomagnetic storms (aa>150 or Ak>50 during either the second half of the nineteenth century or the first decade of the twentieth century are clearly identified by extensive auroral displays observed in China or Japan. Indeed, two of these great storms produced auroral displays observed in both countries on the same night. Conversely, at least 29 (69% of the 42 Chinese and Japanese auroral observations occurred at times of weak-to-moderate geomagnetic activity (aa or Ak≤50. It is shown that these latter auroral displays are very similar to the more numerous (about 50 examples of sporadic aurorae observed in the United States

  20. Sporadic aurorae observed in East Asia

    Directory of Open Access Journals (Sweden)

    D. M. Willis

    2007-03-01

    Full Text Available All the accessible auroral observations recorded in Chinese and Japanese histories during the interval AD 1840–1911 are investigated in detail. Most of these auroral records have never been translated into a Western language before. The East Asian auroral reports provide information on the date and approximate location of each auroral observation, together with limited scientific information on the characteristics of the auroral luminosity such as colour, duration, extent, position in the sky and approximate time of occurrence. The full translations of the original Chinese and Japanese auroral records are presented in an appendix, which contains bibliographic details of the various historical sources. (There are no known reliable Korean observations during this interval. A second appendix discusses a few implausible "auroral" records, which have been rejected. The salient scientific properties of all exactly dated and reliable East Asian auroral observations in the interval AD 1840–1911 are summarised succinctly. By comparing the relevant scientific information on exactly dated auroral observations with the lists of great geomagnetic storms compiled by the Royal Greenwich Observatory, and also the tabulated values of the Ak (Helsinki and aa (Greenwich and Melbourne magnetic indices, it is found that 5 of the great geomagnetic storms (aa>150 or Ak>50 during either the second half of the nineteenth century or the first decade of the twentieth century are clearly identified by extensive auroral displays observed in China or Japan. Indeed, two of these great storms produced auroral displays observed in both countries on the same night. Conversely, at least 29 (69% of the 42 Chinese and Japanese auroral observations occurred at times of weak-to-moderate geomagnetic activity (aa or Ak≤50. It is shown that these latter auroral displays are very similar to the more numerous (about 50 examples of sporadic

  1. Strategies in screening for colon carcinoma

    NARCIS (Netherlands)

    de Wijkerslooth, T. R.; Bossuyt, P. M.; Dekker, E.

    2011-01-01

    Colorectal cancer is the second most common cancer in Europe and meets the criteria for population screening. Population screening should lead to a reduction in CRC-related mortality and incidence. Several options are available for CRC screening, which can be itemised as stool-based tests and

  2. Childhood colorectal carcinoma: A case series | Sharma | African ...

    African Journals Online (AJOL)

    Colorectal carcinoma (CRC) is rare in children, except for a few sporadic reports there is not much information about it in the literature. It is important for pediatricians and paediatric surgeons to be aware that CRC does occur in children, and it should not be excluded only on the basis of the patient\\'s age. Its rarity in children ...

  3. Sonic hedgehog signaling in basal cell carcinomas.

    Science.gov (United States)

    Daya-Grosjean, Leela; Couvé-Privat, Sophie

    2005-07-28

    The development of basal cell carcinoma, the commonest human cancer in fair skinned populations, is clearly associated with constitutive activation of sonic hedgehog signaling. Insight into the genesis of BCC came from the identification of germline mutations of the tumor suppressor gene, PATCHED, a key regulatory component of hedgehog signaling in the nevoid basal cell carcinoma syndrome. Analysis of sporadic basal cell carcinomas and those from repair deficient xeroderma pigmentosum patients has revealed mutational inactivation of PATCHED and gain of function mutations of the proto-oncogenes, SMOOTHENED and SONIC HEDGEHOG associated with solar UV exposure. The molecular mechanisms involved in alterations of the hedgehog signaling pathway that lead to the formation of basal cell carcinomas are being unraveled and has already allowed the investigation of future therapeutic strategies for treating these skin cancers.

  4. A study of tumor makers for thyroid carcinoma

    International Nuclear Information System (INIS)

    Kim, Ok Kyung

    1986-01-01

    Thyroid-associated antigens, such as calcitonin, thyroglobulin and carcinoembryonic antigen(CEA), can be demonstrated by immuno-histochemical detection. The main purpose of this study is to investigate the diagnosis, especially in regard to proving or excluding the thyroid origin of metastasis. A total of 47 cases of the thyroid specimen including 5 colonic and 5 ovarian cancer were studied by immunoperoxidase stain for the distribution and intensity of the calcitonin, thyroglobulin, and CEA. The following results are obtained. 1. The calcitonin reveals diffuse intracellular positivity of only medullary carcinoma, all others are negative. 2. The thyroglobulin show 100% positivity to thyroid adenoma, follicular carcinoma and papillary carcinoma although their intensity and distribution differed in each tumor. 3. The CEA reveals strong positivity of colonic carcinoma and ovarian carcinoma, intracytoplasmic and luminal, as well as moderate positive reaction of follicular carcinoma and papillary carcinoma of throid. In summary, the calcitonin is best tumor marker for medullary carcinoma, where as the thyroglobulin is best for follicullar and paillary carcinoma. The CEA shows variable stain property, but it has a good correlation to diagnosis of colonic carcinoma and ovarian carcinoma. (Author)

  5. The evolving genetic risk for sporadic ALS.

    Science.gov (United States)

    Gibson, Summer B; Downie, Jonathan M; Tsetsou, Spyridoula; Feusier, Julie E; Figueroa, Karla P; Bromberg, Mark B; Jorde, Lynn B; Pulst, Stefan M

    2017-07-18

    To estimate the genetic risk conferred by known amyotrophic lateral sclerosis (ALS)-associated genes to the pathogenesis of sporadic ALS (SALS) using variant allele frequencies combined with predicted variant pathogenicity. Whole exome sequencing and repeat expansion PCR of C9orf72 and ATXN2 were performed on 87 patients of European ancestry with SALS seen at the University of Utah. DNA variants that change the protein coding sequence of 31 ALS-associated genes were annotated to determine which were rare and deleterious as predicted by MetaSVM. The percentage of patients with SALS with a rare and deleterious variant or repeat expansion in an ALS-associated gene was calculated. An odds ratio analysis was performed comparing the burden of ALS-associated genes in patients with SALS vs 324 normal controls. Nineteen rare nonsynonymous variants in an ALS-associated gene, 2 of which were found in 2 different individuals, were identified in 21 patients with SALS. Further, 5 deleterious C9orf72 and 2 ATXN2 repeat expansions were identified. A total of 17.2% of patients with SALS had a rare and deleterious variant or repeat expansion in an ALS-associated gene. The genetic burden of ALS-associated genes in patients with SALS as predicted by MetaSVM was significantly higher than in normal controls. Previous analyses have identified SALS-predisposing variants only in terms of their rarity in normal control populations. By incorporating variant pathogenicity as well as variant frequency, we demonstrated that the genetic risk contributed by these genes for SALS is substantially lower than previous estimates. © 2017 American Academy of Neurology.

  6. Reducing Aircraft Down for Lack of Parts with Sporadic Demand

    National Research Council Canada - National Science Library

    Bachman, Tovey

    2004-01-01

    .... Because of their sporadic demand, it is difficult to decide when to buy these items and in what quantities. As systems become more reliable and failure rates decrease, the number of these infrequently demanded parts is likely to grow...

  7. Updated clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease

    Science.gov (United States)

    Kallenberg, K.; Summers, D. M.; Romero, C.; Taratuto, A.; Heinemann, U.; Breithaupt, M.; Varges, D.; Meissner, B.; Ladogana, A.; Schuur, M.; Haik, S.; Collins, S. J.; Jansen, Gerard H.; Stokin, G. B.; Pimentel, J.; Hewer, E.; Collie, D.; Smith, P.; Roberts, H.; Brandel, J. P.; van Duijn, C.; Pocchiari, M.; Begue, C.; Cras, P.; Will, R. G.; Sanchez-Juan, P.

    2009-01-01

    Several molecular subtypes of sporadic Creutzfeldt–Jakob disease have been identified and electroencephalogram and cerebrospinal fluid biomarkers have been reported to support clinical diagnosis but with variable utility according to subtype. In recent years, a series of publications have demonstrated a potentially important role for magnetic resonance imaging in the pre-mortem diagnosis of sporadic Creutzfeldt–Jakob disease. Magnetic resonance imaging signal alterations correlate with distinct sporadic Creutzfeldt–Jakob disease molecular subtypes and thus might contribute to the earlier identification of the whole spectrum of sporadic Creutzfeldt–Jakob disease cases. This multi-centre international study aimed to provide a rationale for the amendment of the clinical diagnostic criteria for sporadic Creutzfeldt–Jakob disease. Patients with sporadic Creutzfeldt–Jakob disease and fluid attenuated inversion recovery or diffusion-weight imaging were recruited from 12 countries. Patients referred as ‘suspected sporadic Creutzfeldt–Jakob disease’ but with an alternative diagnosis after thorough follow up, were analysed as controls. All magnetic resonance imaging scans were assessed for signal changes according to a standard protocol encompassing seven cortical regions, basal ganglia, thalamus and cerebellum. Magnetic resonance imaging scans were evaluated in 436 sporadic Creutzfeldt–Jakob disease patients and 141 controls. The pattern of high signal intensity with the best sensitivity and specificity in the differential diagnosis of sporadic Creutzfeldt–Jakob disease was identified. The optimum diagnostic accuracy in the differential diagnosis of rapid progressive dementia was obtained when either at least two cortical regions (temporal, parietal or occipital) or both caudate nucleus and putamen displayed a high signal in fluid attenuated inversion recovery or diffusion-weight imaging magnetic resonance imaging. Based on our analyses, magnetic

  8. Role of microsatellite instability in colon cancer

    Directory of Open Access Journals (Sweden)

    M. Yu. Fedyanin

    2012-01-01

    Full Text Available Coloncancer is among leading causes of cancer morbidity and mortality both inRussiaand worldwide. Development of molecular biology lead to decoding of carcinogenesis and tumor progression mechanisms. These processes require accumulation of genetic and epigenetic alterations in a tumor cell.Coloncancer carcinogenesis is characterized by mutations cumulation in genes controlling growth and differentiation of epithelial cells, which leads to their genetic instability. Microsatellite instability is a type of genetic instability characterized by deterioration of mismatch DNA repair. This leads to faster accumulation of mutations in DNA. Loss of mismatch repair mechanism can easily be diagnosed by length of DNA microsatellites. These alterations are termed microsatellite instability. They can be found both in hereditary and sporadic colon cancers. This review covers the questions of microsatellite instability, its prognostic and predictive value in colon cancer.

  9. Angiodysplasia of the colon

    Science.gov (United States)

    Vascular ectasia of the colon; Colonic arteriovenous malformation; Hemorrhage - angiodysplasia; Bleed - angiodysplasia ... Angiodysplasia of the colon is mostly related to the aging and breakdown of the blood vessels. It is more common in older adults. ...

  10. Thymic carcinoma

    Directory of Open Access Journals (Sweden)

    Vitória Homem Machado

    2016-10-01

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

  11. Associations of defect mismatch repair genes with prognosis and heredity in sporadic colorectal cancer.

    Science.gov (United States)

    Ghanipour, L; Jirström, K; Sundström, M; Glimelius, B; Birgisson, H

    2017-02-01

    Microsatellite instability arises due to defect mismatch repair (MMR) and occurs in 10-20% of sporadic colorectal cancer. The purpose was to investigate correlations between defect MMR, prognosis and heredity for colorectal cancer in first-degree relatives. Tumour tissues from 318 patients consecutively operated for colorectal cancer were analysed for immunohistochemical expression of MLH1, MSH2 and MSH6 on tissue microarrays. Information on KRAS and BRAF mutation status was available for selected cases. Forty-seven (15%) tumours displayed MSI. No correlation was seen between patients exhibiting MSI in the tumour and heredity (p = 0.789). Patients with proximal colon cancer and MSI had an improved cancer-specific survival (p = 0.006) and prolonged time to recurrence (p = 0.037). In a multivariate analysis including MSI status, gender, CEA, vascular and neural invasion, patients with MSS and proximal colon cancer had an impaired cancer-specific survival compared with patients with MSI (HR, 4.32; CI, 1.46-12.78). The same prognostic information was also seen in distal colon cancer; no recurrences seen in the eight patients with stages II and III distal colon cancer and MSI, but the difference was not statistically significant. No correlation between MSI and heredity for colorectal cancer in first-degree relatives was seen. Patients with MSI tumours had improved survival. Copyright © 2016 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  12. Volvulus of the sigmoid colon.

    Science.gov (United States)

    Raveenthiran, V; Madiba, T E; Atamanalp, S S; De, U

    2010-07-01

    The current status of sigmoid volvulus (SV) was reviewed to assess trends in management and to assess the literature. The literature on SV was retrieved using PubMed, Embase, Scopus, Pakmedinet, African Journals online (AJOL), Indmed and Google scholar. These databases were searched for text words including 'sigmoid', 'colon' and 'volvulus'. Relevant nonindexed surgical journals published from endemic countries were also manually searched. We focused on original articles published within the last 10 years; but classical references prior to this period were also included. Seminal papers published in non-English languages were also included. Sigmoid volvulus is a leading cause of acute colonic obstruction in South America, Africa, Eastern Europe and Asia. It is rare in developed countries such as USA, UK, Japan and Australia. Characteristic geographic variations in the incidence, clinical features, prognosis and comorbidity of SV justify recognition of endemic and sporadic subtypes. Controversy on aetiologic agents can be minimized by classifying them into 'predisposing' and 'precipitating' factors. Modern imaging systems, although more effective than plain radiographs, are yet to gain popularity. Emergency endoscopic reduction is the treatment of choice in uncomplicated patients. But it is only a temporizing procedure, and it should be followed in most cases by elective definitive surgery. Resection of the redundant sigmoid colon is the gold standard operation. The role of newer nonresective alternatives is yet to be ascertained. Although emergency resection with primary anastomosis (ERPA) has been controversial in the past, it is now increasingly accepted as a safe option with superior results. Management in elderly debilitated patients is extremely difficult. Paediatric SV significantly differs from that in adults. SV is frequently associated with neuropsychiatric diseases, diabetes mellitus and Chagas disease. The overall mortality in recent studies is < 5

  13. Report of a Rare Case of Papillary Thyroid Carcinoma Associated with Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Sh. Borzouei

    2012-10-01

    Full Text Available Introduction: Papillary thyroid cancer (PTC is the most common well-differentiated cancer of the thyroid. Only in few cases of PTC entity of renal cell carcinoma has been observed in patients affected with PTC. Case Report: In this study we report a case of sporadic PTC and renal cell carcinoma in a 63 year-old woman. Conclusion: After surgery the patient was hospitalized for 1 month in ICU section. 3 months after being discharged from the hospital, she was still in a good condition and is under the follow-up treatment.(Sci J Hamadan Univ Med Sci 2012; 19 (3:75-77

  14. Different expression of some molecular markers in sporadic cancer of the left and right colon

    Czech Academy of Sciences Publication Activity Database

    Frič, P.; Sovová, Vlasta; Šloncová, Eva; Lojda, Z.; Jirásek, A.; Čermák, J.

    Roč. 9, č. 4 ( 2000 ), s. 265-268 ISSN 0959-8278 R&D Projects: GA ČR GA312/97/1188; GA AV ČR KSK2039602 Institutional research plan: CEZ:AV0Z5052915 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.351, year: 2000

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

    African Journals Online (AJOL)

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

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

    LENUS (Irish Health Repository)

    Sasi, Walid

    2010-01-01

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

  17. The Prognostic Impact of p53 Expression on Sporadic Colorectal Cancer Is Dependent on p21 Status

    International Nuclear Information System (INIS)

    Kruschewski, Martin; Mueller, Kathrin; Lipka, Sybille; Budczies, Jan; Noske, Aurelia; Buhr, Heinz Johannes; Elezkurtaj, Sefer

    2011-01-01

    The prognostic value of p53 and p21 expression in colorectal cancer is still under debate. We hypothesize that the prognostic impact of p53 expression is dependent on p21 status. The expression of p53 and p21 was immunohistochemically investigated in a prospective cohort of 116 patients with UICC stage II and III sporadic colorectal cancer. The results were correlated with overall and recurrence-free survival. The mean observation period was 51.8 ± 2.5 months. Expression of p53 was observed in 72 tumors (63%). Overall survival was significantly better in patients with p53-positive carcinomas than in those without p53 expression (p = 0.048). No differences were found in recurrence-free survival (p = 0.161). The p53+/p21− combination was seen in 68% (n = 49), the p53+/p21+ combination in 32% (n = 23). Patients with p53+/p21− carcinomas had significantly better overall and recurrence-free survival than those with p53+/p21+ (p < 0.0001 resp. p = 0.003). Our data suggest that the prognostic impact of p53 expression on sporadic colorectal cancer is dependent on p21 status

  18. Western diet enhances benzo(a)pyrene-induced colon tumorigenesis in a polyposis in rat coli (PIRC) rat model of colon cancer.

    Science.gov (United States)

    Harris, Kelly L; Pulliam, Stephanie R; Okoro, Emmanuel; Guo, Zhongmao; Washington, Mary K; Adunyah, Samuel E; Amos-Landgraf, James M; Ramesh, Aramandla

    2016-05-17

    Consumption of Western diet (WD), contaminated with environmental toxicants, has been implicated as one of the risk factors for sporadic colon cancer. Our earlier studies using a mouse model revealed that compared to unsaturated dietary fat, the saturated dietary fat exacerbated the development of colon tumors caused by B(a)P. The objective of this study was to study how WD potentiates B(a)P-induced colon carcinogenesis in the adult male rats that carry a mutation in the Apc locus - the polyposis in the rat colon (PIRC) rats. Groups of PIRC rats were fed with AIN-76A standard diet (RD) or Western diet (WD) and received 25, 50, or 100 μg B(a)P/kg body weight (wt) via oral gavage for 60 days. Subsequent to exposure, rats were euthanized; colons were retrieved and preserved in 10% formalin for counting the polyp numbers, measuring the polyp size, and histological analyses. Blood samples were collected and concentrations of cholesterol, triglycerides, glucose, insulin and leptin were measured. Rats that received WD + B(a)P showed increased levels of cholesterol, triglycerides, and leptin in comparison to RD + B(a)P groups or controls. The colon tumor numbers showed a B(a)P dose-response relationship. Adenomas with high grade dysplasia were prominent in B(a)P + WD rats compared to B(a)P + RD rats and controls (p diet - toxicant interactions in sporadic colon tumor development.

  19. Gene Signature in Sessile Serrated Polyps Identifies Colon Cancer Subtype

    Science.gov (United States)

    Kanth, Priyanka; Bronner, Mary P.; Boucher, Kenneth M.; Burt, Randall W.; Neklason, Deborah W.; Hagedorn, Curt H.; Delker, Don A.

    2016-01-01

    Sessile serrated colon adenoma/polyps (SSA/Ps) are found during routine screening colonoscopy and may account for 20–30% of colon cancers. However, differentiating SSA/Ps from hyperplastic polyps (HP) with little risk of cancer is challenging and complementary molecular markers are needed. Additionally, the molecular mechanisms of colon cancer development from SSA/Ps are poorly understood. RNA sequencing was performed on 21 SSA/Ps, 10 HPs, 10 adenomas, 21 uninvolved colon and 20 control colon specimens. Differential expression and leave-one-out cross validation methods were used to define a unique gene signature of SSA/Ps. Our SSA/P gene signature was evaluated in colon cancer RNA-Seq data from The Cancer Genome Atlas (TCGA) to identify a subtype of colon cancers that may develop from SSA/Ps. A total of 1422 differentially expressed genes were found in SSA/Ps relative to controls. Serrated polyposis syndrome (n=12) and sporadic SSA/Ps (n=9) exhibited almost complete (96%) gene overlap. A 51-gene panel in SSA/P showed similar expression in a subset of TCGA colon cancers with high microsatellite instability (MSI-H). A smaller seven-gene panel showed high sensitivity and specificity in identifying BRAF mutant, CpG island methylator phenotype high (CIMP-H) and MLH1 silenced colon cancers. We describe a unique gene signature in SSA/Ps that identifies a subset of colon cancers likely to develop through the serrated pathway. These gene panels may be utilized for improved differentiation of SSA/Ps from HPs and provide insights into novel molecular pathways altered in colon cancer arising from the serrated pathway. PMID:27026680

  20. Carcinoma caecum - a rare presentation

    International Nuclear Information System (INIS)

    Ali, T.; Mudasser, S.; Mudsser, S.; Sarwar, M.

    2010-01-01

    Caecal and right sided colonic cancers mostly present with fatigue, weakness and iron deficiency anemia. Such tumours rarely perforate posteriorly and involve the retroperitoneum. We report a case of an old Omani lady who came with insidious sign and symptoms of perforated caecum leading to retroperitoneal collection and necrotizing fasciitis of abdominal wall due to carcinoma of caecum. She underwent surgery but despite active intervention, she died because of septicemic shock. (author)

  1. Absence of activating mutations in ras and gsp oncogenes in a cohort of nine patients with sporadic pediatric thyroid tumors.

    Science.gov (United States)

    Pauws, E; Tummers, R F; Ris-Stalpers, C; de Vijlder, J J; Voûte, T

    2001-06-01

    Characterization of the genetic background of pediatric thyroid carcinomas could aid in distinguishing between differently staged tumors with respect to treatment and prognosis. Two known genetic factors associated with thyroid carcinoma, the proto-oncogenes gsp and ras were investigated. DNA was extracted from paraffin sections from both tumor and normal thyroid tissue of nine patients (ages 9-16 years). Of these patients, eight were diagnosed with papillary carcinoma and one with follicular adenoma. The coding exons of gsp and the three known ras genes (H, K, and N-ras) were screened for mutations using SSCP-analysis. There were no mutations present in the ras and gsp proto-oncogenes hot spots, however, LOH of H-ras (chromosome location 11p15.5) was found in tumor tissue from one patient and a homozygous mutation in exon 12 of gsp causing a Pro-->Ser conversion was present in the thyroid tumor tissue from another patient. Two silent polymorphisms were detected, H-ras exon1, 86T-->C and gsp exon 5, 81T-->C. Our results indicate that the ras/gsp mutations found are probably late events in the tumorigenesis representing general oncogenic stress. In conclusion, it seems that ras/gsp activation is not a factor in the mechanism causing sporadic thyroid carcinoma in children. Copyright 2001 Wiley-Liss, Inc.

  2. Title of paper: the induction of P-53 independent programmed cell death (apoptosis) with ionizing radiation and 5-fluorouracil (5-FU) in the HT-29 human colon carcinoma cell line

    International Nuclear Information System (INIS)

    Blackstock, A. Wm.; Gill, Misha; Hess, Suzanne M.; Fisher, Robert W.; Leadon, Steven A.; Tepper, Joel E.

    1996-01-01

    Purpose/Objective: The role of programmed cell death (apoptosis) as a cellular response to cancer therapy such as radiation or chemotherapy is the subject of much study, and manipulation of the apoptotic response in tumor cells may be valuable in the treatment of a variety of cancers. Both p53 dependent and independent apoptotic pathways have been identified; p53 is mutated in at least 50 % of human cancers and a majority of radiation resistant tumors contain p53 mutations. This study is designed to examine the induction of programmed cell death in a human colon carcinoma cell line that possesses two mutated p53 alleles. Ionizing radiation alone, or in combination with the chemotherapeutic drug 5-fluorouracil (5-FU), were used to elicit the apoptotic response. This study will focus on whether these treatments can induce a significant apoptotic response in cells that have mutated p53 alleles. Materials and Methods: HT-29 cells were assessed for clonogenic survival after being plated at a variety of densities, and treated with single graded doses of radiation (0, 1, 2, 4, 6, 8, 10 Gy) either alone or immediately prior to a 24 hour exposure to 5-FU (2 ug/ml). The extent of radiation and 5-FU-induced apoptosis was determined in the HT-29 cell line after single doses of 0, 2, 5, and 10 Gy either alone or immediately prior to a 24 hour incubation in 5-FU (2 ug/ml). Three separate assays were used to evaluate the apoptotic response. Cells undergoing apoptosis undergo gross morphological changes including a condensation of chromatin, membrane blebbing, and an eventual release of membrane bound cytoplasmic fragments. Hematoxylin and eosin staining were used to visualize some of these morphological changes. Another characteristic of the apoptotic response is the activation of an endonuclease that cleaves DNA into specific fragments. Accordingly, an ELISA cell death assay (Boehringer Mannheim, Indianapolis IN) was used to quantitate cytoplasmic histone-associated DNA

  3. Similar phenotype characteristics comparing familial and sporadic premature ovarian failure.

    Science.gov (United States)

    Janse, Femi; Knauff, Erik A H; Niermeijer, Martinus F; Eijkemans, Marinus J; Laven, Joop S E; Lambalk, Cornelius B; Fauser, Bart C J M; Goverde, Angelique J

    2010-07-01

    Premature ovarian failure (POF) is characterized by secondary amenorrhea before the age of 40 years, along with repeated increased follicle-stimulating hormone and low estrogen concentrations. POF is considered a complex genetic disease with a familial presentation in 12% to 50% of cases. POF may originate from different genes and various gene-environment interactions. The aim of this study was to identify possible differences in phenotype comparing women with familial and women with sporadic POF. A multicenter study was initiated in the Netherlands using standardized phenotyping. For each woman, medical history, menstrual cycle, and fertility and smoking status were assessed and a standardized examination was performed. Based on a detailed three-generation family history, women were identified as having either familial (defined as having at least one relative with POF) or sporadic POF. A total of 58 familial cases and 142 sporadic cases of POF were identified. Maternal age at menopause was significantly lower in the women with familial compared with the women with sporadic POF (41.0 +/- 7.5 and 49.7 +/- 2.6 y, respectively; P hormone-binding globulin concentration was significantly higher in the women with familial than in the women with sporadic POF (73.6 +/- 37.1 and 55.2 +/- 26.9 nmol/L, respectively; P = 0.002). All other characteristics, such as parity, bone mineral density, and serum follicle-stimulating hormone and lipid levels were similar, as was the incidence of autoimmunity and cytogenetic abnormalities. Familial and sporadic POF do not differ in phenotype except for maternal menopause age and sex hormone-binding globulin concentration. Future studies are needed to unravel the genotype-phenotype interactions in POF.

  4. BRCA-mutated Invasive Breast Carcinomas: Immunohistochemical Analysis of Insulin-like Growth Factor II mRNA-binding Protein (IMP3), Cytokeratin 8/18, and Cytokeratin 14.

    Science.gov (United States)

    Mohanty, Sambit K; Lai, Jin-Ping; Gordon, Ora K; Pradhan, Dinesh; Bose, Shikha; Dadmanesh, Farnaz

    2015-01-01

    To evaluate the expression of insulin-like growth factor II mRNA-binding protein (IMP3), CK8/18, and CK14 in BRCA mutated and sporadic invasive breast carcinoma. Immunohistochemistry for IMP3, CK8/18, and CK14 was performed on 39 cases of invasive breast carcinomas with BRCA mutation (24 BRCA1, 14 BRCA2, and 1 dual BRCA1/BRCA2) and 54 cases of sporadic invasive breast carcinomas. The relationship between the IMP3, CK8/18, and CK14 and the tumor grade and molecular phenotypes were analyzed. IMP3, CK8/18, and CK14 positivity were present in 20 (51%), 22 (56%), and 14 (36%) of 39 BRCA-mutated breast carcinomas, and 11 (20%), 53 (98%), and 24 (44%) of 54 sporadic breast carcinomas respectively. The rates of IMP3 expression and absence of CK8/18 (44% versus 2%) in BRCA-mutated breast carcinomas was significantly higher than the sporadic breast carcinomas (p = 0.002 and p BRCA1-related and BRCA2-related breast carcinomas in the immunoprofile for IMP3, CK8/18, and CK14. No significant correlation was identified between the expression of IMP3 and CK8/18 and the tumor grade in both BRCA-mutated and sporadic breast carcinomas (p > 0.05). In cases with luminal A and B phenotypes, the rates of expression of IMP3 and loss of CK8/18 were significantly higher in BRCA-mutated as compared to sporadic breast carcinoma (p BRCA-mutated breast carcinomas (54% versus 0%, p = 0.001), while no difference was observed for IMP3 expression (p = 0.435). Regardless of mutation type, histologic grade, or molecular phenotype, the absence of CK8/18 expression and presence of IMP3 expression are seen at much higher rate in BRCA mutated breast carcinomas. © 2015 Wiley Periodicals, Inc.

  5. Squamous Cell Carcinoma

    Science.gov (United States)

    ... Kids’ zone Video library Find a dermatologist Squamous cell carcinoma Overview Squamous cell carcinoma: This man's skin ... a squamous cell carcinoma on his face. Squamous cell carcinoma: Overview Squamous cell carcinoma (SCC) is a ...

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

    Directory of Open Access Journals (Sweden)

    Saad S. Eissa

    2010-04-01

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

  7. PSF3 marks malignant colon cancer and has a role in cancer cell proliferation

    International Nuclear Information System (INIS)

    Nagahama, Yumi; Ueno, Masaya; Haraguchi, Naotsugu; Mori, Masaki; Takakura, Nobuyuki

    2010-01-01

    PSF3 (partner of Sld five 3) is a member of the tetrameric complex termed GINS, composed of SLD5, PSF1, PSF2, and PSF3, and well-conserved evolutionarily. Previous studies suggested that some GINS complex members are upregulated in cancer, but PSF3 expression in colon carcinoma has not been investigated. Here, we established a mouse anti-PSF3 antibody, and examined PSF3 expression in human colon carcinoma cell lines and colon carcinoma specimens. We found that PSF3 is expressed in the crypt region in normal colonic mucosa and that many PSF3-positive cells co-expressed Ki-67. This suggests that PSF3-positivity of normal mucosa is associated with cell proliferation. Expression of the PSF3 protein was greater in carcinoma compared with the adjacent normal mucosa, and even stronger in high-grade malignancies, suggesting that it may be associated with colon cancer progression. PSF3 gene knock-down in human colon carcinoma cell lines resulted in growth inhibition characterized by delayed S-phase progression. These results suggest that PSF3 is a potential biomarker for diagnosis of progression in colon cancer and could be a new target for cancer therapy.

  8. Sporadic potassium layers and their connection to sporadic E layers in the mesopause region at Beijing, China

    Directory of Open Access Journals (Sweden)

    Jing Jiao

    2017-06-01

    Full Text Available A double-laser beam lidar to measure potassium (K layer at Beijing (40.5° N, 116.2° E was successfully developed in 2010. The parameters of sporadic Ks layers and their distributions were given. The seasonal distribution of Ks occurrence frequency was obtained, with two maxima in July and January. The seasonal distributions of sporadic Es layer occurrence frequency over Beijing differ from those of Ks. However, the good correlation between Es and Ks in the case-by-case studies supports the mechanism of neutralization of metal ions in a descending Es layer.

  9. FAP Associated Papillary Thyroid Carcinoma: A Peculiar Subtype of Familial Nonmedullary Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Francesco Cetta

    2015-01-01

    Full Text Available Familial Nonmedullary Thyroid Carcinoma (FNMTC makes up to 5–10% of all thyroid cancers, also including those FNMTC occurring as a minor component of familial cancer syndromes, such as Familial Adenomatous Polyposis (FAP. We give evidence that this extracolonic manifestation of FAP is determined by the same germline mutation of the APC gene responsible for colonic polyps and cancer but also shows some unusual features (F : M ratio = 80 : 1, absence of LOH for APC in the thyroid tumoral tissue, and indolent biological behaviour, despite frequent multicentricity and lymph nodal involvement, suggesting that the APC gene confers only a generic susceptibility to thyroid cancer, but perhaps other factors, namely, modifier genes, sex-related factors, or environmental factors, are also required for its phenotypic expression. This great variability is against the possibility of classifying all FNMTC as a single entity, not only with a unique or prevalent causative genetic factor, but also with a unique or common biological behavior and a commonly dismal prognosis. A new paradigm is also suggested that could be useful (1 for a proper classification of FAP associated PTC within the larger group of FNMTC and (2 for making inferences to sporadic carcinogenesis, based on the lesson from FAP.

  10. Brain sonography in African infants with complicated sporadic ...

    African Journals Online (AJOL)

    Background: To determine the structural findings in brain sonography of African infants with complicated sporadic bacterial meningitis. Materials and Methods: Retrospective assessment of medical records of patients who underwent brain sonography on account of complicated bacterial meningitis. The brain sonography ...

  11. Updated clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease

    NARCIS (Netherlands)

    I. Zerr; K. Kallenberg; D.M. Summers; C. Romero; A. Taratuto; U. Heinemann; M. Breithaupt; D. Varges; B. Meissner; A. Ladogana (Anna); M. Schuur (Maaike); S. Haik; S.J. Collins (Steven); G.H. Jansen (Gerard); G.B. Stokin; J. Pimentel; E. Hewer; D. Collie; P. Smith; H. Roberts; J.P. Brandel; P. Tikka-Kleemola (Päivi); M. Pocchiari (Maurizio); C. Begue; P. Cras (Patrick); R.G. Will; P. Sanchez-Juan (Pascual)

    2009-01-01

    textabstractSeveral molecular subtypes of sporadic Creutzfeldt-Jakob disease have been identified and electroencephalogram and cerebrospinal fluid biomarkers have been reported to support clinical diagnosis but with variable utility according to subtype. In recent years, a series of publications

  12. Comparing Sporadic and Outbreak-associated Foodborne Illness

    Centers for Disease Control (CDC) Podcasts

    2016-11-04

    Dr. Eric Ebel, a veterinarian and risk analyst with USDA’s Food Safety and Inspection Service, discusses his article on sporadic and outbreak-associated cases of foodborne illness.  Created: 11/4/2016 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 11/4/2016.

  13. Prevalence of Abnormal Cervical Smears from Sporadic Screening ...

    African Journals Online (AJOL)

    The aim of the study was to find the prevalence of abnormal smears in an unscreened population of sexually active women attending a gynaecological clinic. “Pap” smears were taken sporadically for cytological examination from sexually active women attending gynaecological clinics at the Federal Medical Centre Gombe.

  14. Legionnaires’ Disease: Clinicoradiological Comparison of Sporadic Versus Outbreak Cases

    Directory of Open Access Journals (Sweden)

    Hafiz Rizwan Talib Hashmi

    2017-06-01

    Full Text Available Background: In 2015, New York City experienced the worst outbreak of Legionnaires’ disease in the history of the city. We compare patients seen during the 2015 outbreak with sporadic cases of Legionella during the past 5 years. Methods: We conducted a retrospective chart review of 90 patients with Legionnaires’ disease, including sporadic cases of Legionella infection admitted from 2010 to 2015 (n = 55 and cases admitted during the 2015 outbreak (n = 35. Results: We saw no significant differences between the 2 groups regarding demographics, smoking habits, alcohol intake, underlying medical disease, or residence type. Univariate and multivariate analyses showed that patients with sporadic case of Legionella had a longer stay in the hospital and intensive care unit as well as an increased stay in mechanical ventilation. Short-term mortality, discharge disposition, and most clinical parameters did not differ significantly between the 2 groups. Conclusions: We found no specific clinicoradiological characteristics that could differentiate sporadic from epidemic cases of Legionella . Early recognition and high suspicion for Legionnaires’ disease are critical to provide appropriate treatment. Cluster of cases should increase suspicion for an outbreak.

  15. Cyclin D1 genotype and expression in sporadic hemangioblastomas.

    NARCIS (Netherlands)

    Gijtenbeek, J.M.M.; Sprenger, S.H.E.; Franke, B.; Wesseling, P.; Jeuken, J.W.M.

    2005-01-01

    Central nervous system (CNS) hemangioblastomas are highly-vascularized tumors occurring in sporadic form or as a manifestation of von Hippel-Lindau disease (VHL). The VHL protein (pVHL) regulates various target genes, one of which is the CCND1 gene, encoding cyclin D1, a protein that plays a

  16. Dyschromatosis symmetrica hereditaria: Report of a sporadic case ...

    African Journals Online (AJOL)

    ... hands and feet, with no family history of similar lesions. The diagnosis was confirmed by the typical histologic finding of basal hyperpigmentation with normal number of melanocytes and absence of melanin incontinence from a hyperpigmented lesion. Keywords: DyschromatosisSymmetricaHereditaria, Nigerian, Sporadic ...

  17. Interpretation of electrodiagnostic findings in sporadic progressive muscular atrophy

    NARCIS (Netherlands)

    Visser, J.; de Visser, M.; van den Berg-Vos, R. M.; van den Berg, L. H.; Wokke, J. H. J.; de Jong, J. M. B. V.; Franssen, H.

    2008-01-01

    Objective We present the electrophysiologic data at baseline of 37 patients who were included in our prospective study on sporadic adult-onset progressive muscular atrophy (PMA). The aim was to correlate electrophysiological. signs of lower motor neuron (LMN) loss with clinical signs of LMN loss,

  18. [The practice guideline 'Dermatomyositis, polymyositis and sporadic inclusion body myositis'

    NARCIS (Netherlands)

    Hoogendijk, J.E.; Bijlsma, J.W.J.; Engelen, B.G.M. van; Lindeman, E.J.M.; Royen-Kerkhof, A. van; Rie, M.A. de; Visser, M. de; Jennekens, F.G.I.

    2005-01-01

    This guideline presents recommendations for the diagnosis and treatment of dermatomyositis, polymyositis and sporadic inclusion body myositis (sIBM) according to the best available evidence. Characteristic skin abnormalities can be sufficient for the diagnosis of dermatomyositis. In case of doubt, a

  19. Sex disparity in colonic adenomagenesis involves promotion by male hormones, not protection by female hormones

    NARCIS (Netherlands)

    Amos-Landgraf, James M.; Heijmans, Jarom; Wielenga, Mattheus C. B.; Dunkin, Elisa; Krentz, Kathy J.; Clipson, Linda; Ederveen, Antwan G.; Groothuis, Patrick G.; Mosselman, Sietse; Muncan, Vanesa; Hommes, Daniel W.; Shedlovsky, Alexandra; Dove, William F.; van den Brink, Gijs R.

    2014-01-01

    It recently has been recognized that men develop colonic adenomas and carcinomas at an earlier age and at a higher rate than women. In the Apc(Pirc/+) (Pirc) rat model of early colonic cancer, this sex susceptibility was recapitulated, with male Pirc rats developing twice as many adenomas as

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

    NARCIS (Netherlands)

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

    2010-01-01

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

  1. Parotid carcinoma

    DEFF Research Database (Denmark)

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

    2006-01-01

    OBJECTIVES: Our aim is to investigate the expression of kit protein (KIT) and epidermal growth factor receptor (EGFR) in parotid carcinomas in order to correlate the expression to histology and prognosis. Further we want to perform mutation analysis of KIT-positive adenoid cystic carcinomas. PATI...

  2. Basisquamous Carcinoma

    Directory of Open Access Journals (Sweden)

    Yesudian Devakar P

    1997-01-01

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

  3. Serous tubal intraepithelial carcinoma, chronic fallopian tube injury, and serous carcinoma development.

    Science.gov (United States)

    Malmberg, Karin; Klynning, Charlotta; Flöter-Rådestad, Angelique; Carlson, Joseph W

    2016-06-01

    Ovarian carcinoma is the deadliest gynecological malignancy. Previous studies have suggested that the fallopian tube may be the primary site for high-grade serous carcinoma. In prophylactic salpingo-oophorectomies from women with hereditary high risk for ovarian cancer, precursors can be assessed prior to onset and studied as a model for serous cancer precursor lesions. Epidemiologic studies indicate that carcinogenesis may be a result of chronic fallopian tube injury. The aims of this study were to (1) to examine the incidence of serous tubal intraepithelial carcinoma (STIC) in relation to other clinical parameters and (2) to evaluate whether chronic fallopian tube injury was related to cancer development. This study enrolled 101 women, comprising the following three groups: hereditary (n = 60), sporadic serous cancer (n = 18; endometrial cancers were excluded), and control (n = 23). The cases were histologically examined and clinical risk factors were collected. The histological changes were compared between different patients and correlated to clinical risk factors. STICs were identified primarily on the fallopian tube fimbria. The incidence of STIC was 3 % in the hereditary patients. In sporadic serous cancer cases, 61 % were associated with STIC and tubal carcinoma (p STIC and invasive cancer were seen more often in the older patients than in the younger patients (p = 0.528). This small study, no correlation with chronic tubal injury or inflammation was identified.

  4. Mesenchymal Cells in Colon Cancer.

    Science.gov (United States)

    Koliaraki, Vasiliki; Pallangyo, Charles K; Greten, Florian R; Kollias, George

    2017-04-01

    Mesenchymal cells in the intestine comprise a variety of cell types of diverse origins, functions, and molecular markers. They provide mechanical and structural support and have important functions during intestinal organogenesis, morphogenesis, and homeostasis. Recent studies of the human transcriptome have revealed their importance in the development of colorectal cancer, and studies from animal models have provided evidence for their roles in the pathogenesis of colitis-associated cancer and sporadic colorectal cancer. Mesenchymal cells in tumors, called cancer-associated fibroblasts, arise via activation of resident mesenchymal cell populations and the recruitment of bone marrow-derived mesenchymal stem cells and fibrocytes. Cancer-associated fibroblasts have a variety of activities that promote colon tumor development and progression; these include regulation of intestinal inflammation, epithelial proliferation, stem cell maintenance, angiogenesis, extracellular matrix remodeling, and metastasis. We review the intestinal mesenchymal cell-specific pathways that regulate these processes, with a focus on their roles in mediating interactions between inflammation and carcinogenesis. We also discuss how increasing our understanding of intestinal mesenchymal cell biology and function could lead to new strategies to identify and treat colitis-associated cancers. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

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

    OpenAIRE

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

    2014-01-01

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

  6. Colon diverticula - slideshow

    Science.gov (United States)

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

  7. Breast imaging findings in women with BRCA1- and BRCA2-associated breast carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Hamilton, L.J.; Evans, A.J. E-mail: aevans@ncht.trent.nhs.uk; Wilson, A.R.M.; Scott, N.; Cornford, E.J.; Pinder, S.E.; Khan, H.N.; Macmillan, R.D

    2004-10-01

    AIM: To document the breast imaging findings of women with BRCA1 and BRCA2-associated breast carcinoma. MATERIALS AND METHODS: Family history clinic records identified 18 BRCA1 and 10 BRCA2 cases who collectively were diagnosed with 27 invasive breast carcinomas and four ductal carcinoma in situ (DCIS) lesions. All underwent pre-operative imaging (29 mammogram and 22 ultrasound examinations). All invasive BRCA-associated breast carcinoma cases were compared with age-matched cases of sporadic breast carcinoma. RESULTS: Within the BRCA cases the age range was 26-62 years, mean 36 years. Two mammograms were normal and 27 (93%) abnormal. The most common mammographic features were defined mass (63%) and microcalcifications (37%). Thirty-four percent of women had a dense mammographic pattern, 59% mixed and 7% fatty. Ultrasound was performed in 22 patients and in 21 (95%) indicated a mass. This was classified as benign in 24%, indeterminate in 29% and malignant in 48%. Mammograms of BRCA1-associated carcinomas more frequently showed a defined mass compared with BRCA2-associated carcinomas, 72 versus 36% (73% control group) whilst mammograms of BRCA2-associated carcinomas more frequently showed microcalcification, 73 versus 12% (8% control group; p<0.001). Thirty-six percent of the BRCA2-associated carcinomas were pure DCIS while none of the BRCA1 associated carcinomas were pure DCIS (p=0.004). Of those patients undergoing regular mammographic screening, 100% of BRCA2-associated carcinomas were detected compared with 75% of BRCA1-associated carcinomas. CONCLUSION: These data suggest that the imaging findings of BRCA1 and BRCA2-associated carcinomas differ from each other and from age-matched cases of sporadic breast carcinoma.

  8. Induction of basal cell carcinomas and trichoepitheliomas in mice overexpressing GLI-1

    OpenAIRE

    Nilsson, Mats; Undèn, Anne Birgitte; Krause, Darren; Malmqwist, Ulrica; Raza, Karima; Zaphiropoulos, Peter G.; Toftgård, Rune

    2000-01-01

    Basal cell carcinoma is the most prevalent cancer in the western world, showing a rapid increase in incidence. Activation of the Sonic hedgehog/Patched (PTCH) signaling pathway because of PTCH1 inactivation is a key event in sporadic and familial basal cell carcinoma development in humans and is associated with transcriptional activation of specific target genes, including PTCH1 itself. These changes are analogous to the situation in Drosophila where hedgehog activates the zinc-finger transcr...

  9. Imaging analysis of colonic villous tumors

    International Nuclear Information System (INIS)

    Lee, Choon Hyeong; Lim, Joo Won; Lee, Dong Ho; Ko, Yung Tae; Yang, Ik

    1996-01-01

    To evaluate the CT and US features of the colonic villous tumors. We retrospectively reviewed the CT findings of 11 cases with histologically proved colonic villous tumor. CT parameters evaluated were morphological appearances and enhancing pattern (size, shape, margin, presence or absence of fronds, bowel wall thickening). CT features of six cases with malignant change were compared with five tumors without malignant change. US features available in 10 patients were also analyzed. On CT, the tumors showed irregular margin(n=9), presence of fronds(n=6), lobulated shape(n=11), with pericolonic invasion(n=1). Six cases with malignant change were larger(mean, 6.8 cm in diameter) than those without malignant change(mean, 3.3cm). US features in 10 cases were intraluminal mass(n=5), colonic wall thickening(n=5), with variable echogenicity. Colonic villous tumor appeared as a nonspecific mass on CT and US with a difficulty in distinguishing from colon carcinoma

  10. White matter involvement in sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Caverzasi, Eduardo; Mandelli, Maria Luisa; DeArmond, Stephen J; Hess, Christopher P; Vitali, Paolo; Papinutto, Nico; Oehler, Abby; Miller, Bruce L; Lobach, Irina V; Bastianello, Stefano; Geschwind, Michael D; Henry, Roland G

    2014-12-01

    Sporadic Creutzfeldt-Jakob disease is considered primarily a disease of grey matter, although the extent of white matter involvement has not been well described. We used diffusion tensor imaging to study the white matter in sporadic Creutzfeldt-Jakob disease compared to healthy control subjects and to correlated magnetic resonance imaging findings with histopathology. Twenty-six patients with sporadic Creutzfeldt-Jakob disease and nine age- and gender-matched healthy control subjects underwent volumetric T1-weighted and diffusion tensor imaging. Six patients had post-mortem brain analysis available for assessment of neuropathological findings associated with prion disease. Parcellation of the subcortical white matter was performed on 3D T1-weighted volumes using Freesurfer. Diffusion tensor imaging maps were calculated and transformed to the 3D-T1 space; the average value for each diffusion metric was calculated in the total white matter and in regional volumes of interest. Tract-based spatial statistics analysis was also performed to investigate the deeper white matter tracts. There was a significant reduction of mean (P=0.002), axial (P=0.0003) and radial (P=0.0134) diffusivities in the total white matter in sporadic Creutzfeldt-Jakob disease. Mean diffusivity was significantly lower in most white matter volumes of interest (PCreutzfeldt-Jakob disease. Mean diffusivity reduction reflected concomitant decrease of both axial and radial diffusivity, without appreciable changes in white matter anisotropy. Tract-based spatial statistics analysis showed significant reductions of mean diffusivity within the white matter of patients with sporadic Creutzfeldt-Jakob disease, mainly in the left hemisphere, with a strong trend (P=0.06) towards reduced mean diffusivity in most of the white matter bilaterally. In contrast, by visual assessment there was no white matter abnormality either on T2-weighted or diffusion-weighted images. Widespread reduction in white matter mean

  11. Oncogenic K-ras promotes early carcinogenesis in the mouse proximal colon

    Science.gov (United States)

    Calcagno, Shelly R.; Li, Shuhua; Colon, Migdalisel; Kreinest, Pamela A.; Thompson, E. Aubrey; Fields, Alan P.; Murray, Nicole R.

    2014-01-01

    Oncogenic K-ras mutations are frequently observed in colon cancers and contribute to transformed growth. Oncogenic K-ras is detected in aberrant crypt foci (ACF), precancerous colonic lesions, demonstrating that acquisition of a K-ras mutation is an early event in colon carcinogenesis. Here, we investigate the role of oncogenic K-ras in neoplastic initiation and progression. Transgenic mice in which an oncogenic K-rasG12D allele is activated in the colonic epithelium by sporadic recombination (K-rasLA2 mice) develop spontaneous ACF that are morphologically indistinguishable from those induced by the colon carcinogen azoxymethane (AOM). Similar neoplastic changes involving the entire colon are induced in transgenic mice constitutively expressing K-rasG12D throughout the colon (LSL-K-rasG12D/Villin-Cre mice). However, the biochemistry and fate of K-ras-induced lesions differ depending upon their location within the colon in these mice. In the proximal colon, K-rasG12D induces increased expression of procarcinogenic protein kinase CβII (PKCβII), activation of the MEK/ERK signaling axis and increased epithelial cell proliferation. In contrast, in the distal colon, K-rasG12D inhibits expression of procarcinogenic PKCβII and induces apoptosis. Treatment of K-rasLA2 mice with AOM leads to neoplastic progression of small ACF to large, dysplastic microadenomas in the proximal, but not the distal colon. Thus, oncogenic K-ras functions differently in the proximal and distal colon of mice, inducing ACF capable of neoplastic progression in the proximal colon, and ACF with little or no potential for progression in the distal colon. Our data indicate that acquisition of a K-ras mutation is an initiating neoplastic event in proximal colon cancer development in mice. PMID:18271008

  12. Prospective evaluation of laparoscopic colon resection versus open colon resection for adenocarcinoma. A multicenter study.

    Science.gov (United States)

    Franklin, M E; Rosenthal, D; Norem, R F

    1995-07-01

    Laparoscopic colon resection (LCR) has been performed in the United States sine 1990. This procedure has been accepted by many as a reasonable alternative for nonmalignant, colonic, surgical disease, but the laparoscopic approach remains controversial for curative treatment of carcinoma. In this paper, the results of a nonrandomized series of two large experiences of laparoscopic colon resections were performed and followed for 3 1/2 years in a prospective fashion against an equal number of patients who underwent open resection. The setting was several large metropolitan hospitals in San Antonio, Texas. Over 194 patients were involved in this study. Each patient once diagnosed with resectable colonic cancer was allowed to choose their own procedure, laparoscopic or open colon resection, either of which was performed by the authors. Factors considered include age, sex, body habitus, stage of cancer, margins of resection, numbers of lymph nodes retrieved, hospitalization time, and follow-up period. Observations at this time indicate the following: (1) LCR allows for resection comparable to the classical approach, (2) equal numbers of mesenteric lymph nodes can be retrieved, (3) adequacy of margins of resection can be accurately determined by colonoscopy during LCR, and (4) brief follow-up periods show comparable survival and disease-free intervals. It is the conclusion of the authors that with proper training LCR will come to be recognized as a safe, effective surgical option for treatment of selected patients with colon cancer.

  13. Basal cell carcinoma: pathophysiology.

    Science.gov (United States)

    Sehgal, Virendra N; Chatterjee, Kingshuk; Pandhi, Deepika; Khurana, Ananta

    2014-01-01

    Basal cell carcinoma (BCC) is the most common skin cancer in humans, which typically appears over the sun-exposed skin as a slow-growing, locally invasive lesion that rarely metastasizes. Although the exact etiology of BCC is unknown, there exists a well-established relationship between BCC and the pilo-sebaceous unit, and it is currently thought to originate from pluri-potential cells in the basal layer of the epidermis or the follicle. The patched/hedgehog intracellular signaling pathway plays a central role in both sporadic BCCs and nevoid BCC syndrome (Gorlin syndrome). This pathway is vital for the regulation of cell growth, and differentiation and loss of inhibition of this pathway is associated with development of BCC. The sonic hedgehog protein is the most relevant to BCC; nevertheless, the Patched (PTCH) protein is the ligand-binding component of the hedgehog receptor complex in the cell membrane. The other protein member of the receptor complex, smoothened (SMO), is responsible for transducing hedgehog signaling to downstream genes, leading to abnormal cell proliferation. The importance of this pathway is highlighted by the successful use in advanced forms of BCC of vismodegib, a Food and Drug Administration-approved drug, that selectively inhibits SMO. The UV-specific nucleotide changes in the tumor suppressor genes, TP53 and PTCH, have also been implicated in the development of BCC.

  14. Systematic comparison of sporadic and syndromic pancreatic islet cell tumors.

    Science.gov (United States)

    Erlic, Zoran; Ploeckinger, Ursula; Cascon, Alberto; Hoffmann, Michael M; von Duecker, Laura; Winter, Aurelia; Kammel, Gerit; Bacher, Janina; Sullivan, Maren; Isermann, Berend; Fischer, Lars; Raffel, Andreas; Knoefel, Wolfram Trudo; Schott, Matthias; Baumann, Tobias; Schaefer, Oliver; Keck, Tobias; Baum, Richard P; Milos, Ioana; Muresan, Mihaela; Peczkowska, Mariola; Januszewicz, Andrzej; Cupisti, Kenko; Tönjes, Anke; Fasshauer, Mathias; Langrehr, Jan; von Wussow, Peter; Agaimy, Abbas; Schlimok, Günter; Lamberts, Regina; Wiech, Thorsten; Schmid, Kurt Werner; Weber, Alexander; Nunez, Mercedes; Robledo, Mercedes; Eng, Charis; Neumann, Hartmut P H

    2010-12-01

    Pancreatic islet cell tumors (ICTs) occur as sporadic neoplasias or as a manifestation of multiple endocrine neoplasia type 1 (MEN1) and von Hippel-Lindau disease (VHL). Molecular classification of ICTs is mandatory for timely diagnosis and surveillance. Systematic comparison of VHL-ICTs and sporadic ICTs has been lacking. Our registry-based approaches used the German NET-Registry with 259 patients with neuroendocrine tumors (NETs), who were primarily diagnosed with NETs, and the German VHL-Registry with 485 molecular genetically confirmed patients who had undergone magnetic resonance imaging or computed tomography of the abdomen. All patients provided blood DNA for testing of the MEN1 and VHL genes for intragenic mutations and large deletions. In the NET-Registry, 9/101 patients (8.9%) with ICTs had germline mutations, 8 in MEN1 and 1 in VHL. In the VHL-Registry, prevalence of NETs was 52/487 (10.6%), and all were ICTs. Interestingly, of those with VHL p.R167W, 47% developed ICTs, compared to 2% of those with p.Y98H. In total, there were 92 truly sporadic, i.e. mutation-negative ICT patients. Comparing these with the 53 VHL-ICT patients, the statistically significant differences were predominance of female gender (P=0.01), multifocal ICTs (P=0.0029), and lower malignancy rate (PICTs compared to sporadic cases. VHL was prevalent in ICTs, which are rarely the first presentation. Patients with NETs should not be subjected to genetic testing of the VHL gene, unless they have multifocal ICTs, other VHL-associated tumors, and/or a family history for VHL.

  15. The Role of Iron In Sporadic E Layers

    Science.gov (United States)

    Vondrak, T.; Woodcock, K. R. I.; Plane, J. M. C.

    Sporadic E layers in the lower thermosphere are mostly composed of metallic ions, of which Fe+ is the most abundant. Because dielectric recombination (Fe+ + elec- tron) is very slow, the lifetime of Fe+ above about 100 km is at least several days. However, below this height molecular ions such as FeO+, FeO2+ and FeN2+ form in- creasingly rapidly through reactions with O3, O2 and N2, respectively. These undergo rapid dissociative recombination with electrons, causing Fe+ to be neutralised increas- ingly rapidly as a sporadic E layer descends. Indeed, this is the most likely mechanism for the formation of the sporadic neutral Fe layers that are observed by lidar. However, atomic O plays a very important role in reducing these molecular ions back to Fe+, competing with dissociative recombination and thus slowing the rate at which Fe+ is neutralised and a sporadic E layer dissipates. This paper will discuss a laboratory and modelling study of the reactions of FeO+, FeO2+ and FeN2+ with atomic O. These reactions were studied (for the first time) in a fast flow tube, using the pulsed laser ablation of a rotating iron rod as the source of Fe+ ions in the upstream section of the tube. Reactants were then added to produce molecular ions, and atomic O further downstream through a movable injector. Fe+ and the molecular ions were detected at the downstream end of the tube using a two-stage quadrupole mass spectrometer. The spectroscopy of the FeO+ ion, observed by laser induced fluorescence, will also be discussed as a candidate for future ground-based lidar studies of the ion chemistry of the lower thermosphere.

  16. Measurements of the ionization heights of sporadic radio-meteors

    International Nuclear Information System (INIS)

    Baggaley, W.J.; Webb, T.H.

    1980-01-01

    The echo heights and echo point ionization densities of 4587 sporadic radio-meteors have been determined using a calibrated interferometric height-finding system. Over the height interval 92 to 96 km no association was found between height and ionization but, for radio-meteors ablating above and below this region, significant and opposite trends exist in the data. It is suggested that this could be evidence for the influx of two distinct meteoroid populations. (author)

  17. No evidence for mutations in exons 1, 8 and 18 of the patched gene in sporadic skin lesions of Brazilian patients

    Directory of Open Access Journals (Sweden)

    Granja F.

    2003-01-01

    Full Text Available There is strong evidence that the patched (PTCH gene is a gene for susceptibility to the nevoid basal cell carcinoma syndrome. PTCH has also been shown to mutate in both familial and sporadic basal cell carcinomas. However, mutations of the gene seem to be rare in squamous cell carcinomas. In order to characterize the role of the gene in the broader spectrum of sporadic skin malignant and pre-malignant lesions, we performed a polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP analysis of genomic DNA extracted from 105 adult patients (46 females and 59 males. There were 66 patients with basal cell carcinomas, 30 with squamous cell carcinomas, 2 with malignant melanomas and 7 patients with precancerous lesions. Two tissue samples were collected from each patient, one from the central portion of the tumor and another from normal skin. Using primers that encompass the entire exon 1, exon 8 and exon 18, where most of the mutations have been detected, we were unable to demonstrate any band shift. Three samples suspected to present aberrant migrating bands were excised from the gel and sequenced directly. In addition, we sequenced 12 other cases, including tumors and corresponding normal samples. A wild-type sequence was found in all 15 cases. Although our results do not exclude the presence of clonal alterations of the PTCH gene in skin cancers or mutations in other exons that were not screened, the present data do not support the presence of frequent mutations reported for non-melanoma skin cancer of other populations.

  18. MR imaging of colorectal carcinomas using an MR endoscopic coil

    International Nuclear Information System (INIS)

    Murano, Akihiko; Kido, Choichiro; Sasaki, Fumio; Nakamura, Tsuneya; Kobayashi, Semi; Katoh, Tomoyuki; Hirai, Takashi

    1994-01-01

    Diagnosis of the depth of wall invasion by rectal carcinoma using MR endoscopy was performed in ten resected specimens, including five rectal carcinomas, three colon carcinomas, two normal gastric wall. In addition, the gastric wall of a pig was examined. MR imaging was done with a 1.5-T Signa Advantage (GE Medical System) system, with the surface coil of the MR endoscope acting as the receiver coil. Five layers could be distinguished in the bowel wall: mucosa, submucosa and muscularis propria divided into circular muscle, longitudinal muscle and intervening connective tissue. Tumors had almost the same signal intensity as muscle. The MR images of colon carcinomas, rectal carcinomas, and extrinsically metastatic involvement of the sigmoid colon by rectal carcinoma all correlated well with the pathological findings. The normal structure of the gastric wall was similar to that of the colon. 3D-fast Spoiled Grass (SPGR) sequence has a fairly short scanning time. Thus, the possibility of precise clinical diagnosis by this method was suggested. (author)

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

    Science.gov (United States)

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

    2018-01-01

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

  20. Anaplastic carcinoma

    International Nuclear Information System (INIS)

    Parikh, D.M.; Agarwal, S.; Rao, R.S.

    1999-01-01

    Thyroid carcinoma (TC) is a slow growing tumor with an indolent course and has an excellent prognosis. However, a sharp contrast exists in the biological behavior of TC, which in its well-differentiated form is associated with long-term survival, but in its undifferentiated form is one of the most lethal neoplasms known. The anaplastic carcinoma (ANC) form has a fulminanat course with poor prognosis and almost invariably, a fatal outcome

  1. DNA mismatch repair defects and microsatellite instability status in periocular sebaceous carcinoma.

    Science.gov (United States)

    Rajan Kd, Anand; Burris, Christopher; Iliff, Nicholas; Grant, Michael; Eshleman, James R; Eberhart, Charles G

    2014-03-01

    To characterize mismatch repair protein expression and the role of DNA repair abnormalities in sebaceous carcinomas of the ocular adnexa. Retrospective case-series study. We reviewed 10 cases of sporadic sebaceous carcinoma and 1 case involving a patient with a family history consistent with Muir-Torre syndrome. Immunohistochemistry was used to analyze the presence of 4 mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2) in these tumors. DNA was extracted from 7 of the larger tumors as well as from adjacent normal control tissue and microsatellite instability (MSI) analysis using 5 highly sensitive mononucleotides and 2 pentanucleotides was performed. All 10 sporadic periocular sebaceous carcinomas maintained strong staining of the 4 mismatch repair genes, while tumor from the patient with Muir-Torre syndrome showed loss of staining for the mismatch repair genes MSH2 and MSH6. MSI testing of 7 tumors identified no changes in sporadic cases and yielded results supporting presence of repeat sequence instability in the Muir-Torre-associated case. Sporadic sebaceous carcinoma of the ocular adnexa is not commonly associated with a loss of mismatch repair genes or microsatellite instability. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Screening of hypoxia-inducible genes in sporadic ALS.

    LENUS (Irish Health Repository)

    Cronin, Simon

    2008-10-01

    Genetic variations in two hypoxia-inducible angiogenic genes, VEGF and ANG, have been linked with sporadic amyotrophic lateral sclerosis (SALS). Common variations in these genes may reduce the levels or functioning of their products. VEGF and ANG belong to a larger group of angiogenic genes that are up-regulated under hypoxic conditions. We hypothesized that common genetic variation across other members of this group may also predispose to sporadic ALS. To screen other hypoxia-inducible angiogenic genes for association with SALS, we selected 112 tagging single nucleotide polymorphisms (tgSNPs) that captured the common genetic variation across 16 VEGF-like and eight ANG-like hypoxia-inducible genes. Screening for association was performed in 270 Irish individuals with typical SALS and 272 ethnically matched unrelated controls. SNPs showing association in the Irish phase were genotyped in a replication sample of 281 Swedish sporadic ALS patients and 286 Swedish controls. Seven markers showed association in the Irish. The one modest replication signal observed in the Swedish replication sample, at rs3801158 in the gene inhibin beta A, was for the opposite allele vs. the Irish cohort. We failed to detect association of common variation across 24 candidate hypoxia-inducible angiogenic genes with SALS.

  3. Next generation sequencing in sporadic retinoblastoma patients reveals somatic mosaicism.

    Science.gov (United States)

    Amitrano, Sara; Marozza, Annabella; Somma, Serena; Imperatore, Valentina; Hadjistilianou, Theodora; De Francesco, Sonia; Toti, Paolo; Galimberti, Daniela; Meloni, Ilaria; Cetta, Francesco; Piu, Pietro; Di Marco, Chiara; Dosa, Laura; Lo Rizzo, Caterina; Carignani, Giulia; Mencarelli, Maria Antonietta; Mari, Francesca; Renieri, Alessandra; Ariani, Francesca

    2015-11-01

    In about 50% of sporadic cases of retinoblastoma, no constitutive RB1 mutations are detected by conventional methods. However, recent research suggests that, at least in some of these cases, there is somatic mosaicism with respect to RB1 normal and mutant alleles. The increased availability of next generation sequencing improves our ability to detect the exact percentage of patients with mosaicism. Using this technology, we re-tested a series of 40 patients with sporadic retinoblastoma: 10 of them had been previously classified as constitutional heterozygotes, whereas in 30 no RB1 mutations had been found in lymphocytes. In 3 of these 30 patients, we have now identified low-level mosaic variants, varying in frequency between 8 and 24%. In 7 out of the 10 cases previously classified as heterozygous from testing blood cells, we were able to test additional tissues (ocular tissues, urine and/or oral mucosa): in three of them, next generation sequencing has revealed mosaicism. Present results thus confirm that a significant fraction (6/40; 15%) of sporadic retinoblastoma cases are due to postzygotic events and that deep sequencing is an efficient method to unambiguously distinguish mosaics. Re-testing of retinoblastoma patients through next generation sequencing can thus provide new information that may have important implications with respect to genetic counseling and family care.

  4. Stable and sporadic symbiotic communities of coral and algal holobionts

    Science.gov (United States)

    Hester, Eric R; Barott, Katie L; Nulton, Jim; Vermeij, Mark JA; Rohwer, Forest L

    2016-01-01

    Coral and algal holobionts are assemblages of macroorganisms and microorganisms, including viruses, Bacteria, Archaea, protists and fungi. Despite a decade of research, it remains unclear whether these associations are spatial–temporally stable or species-specific. We hypothesized that conflicting interpretations of the data arise from high noise associated with sporadic microbial symbionts overwhelming signatures of stable holobiont members. To test this hypothesis, the bacterial communities associated with three coral species (Acropora rosaria, Acropora hyacinthus and Porites lutea) and two algal guilds (crustose coralline algae and turf algae) from 131 samples were analyzed using a novel statistical approach termed the Abundance-Ubiquity (AU) test. The AU test determines whether a given bacterial species would be present given additional sampling effort (that is, stable) versus those species that are sporadically associated with a sample. Using the AU test, we show that coral and algal holobionts have a high-diversity group of stable symbionts. Stable symbionts are not exclusive to one species of coral or algae. No single bacterial species was ubiquitously associated with one host, showing that there is not strict heredity of the microbiome. In addition to the stable symbionts, there was a low-diversity community of sporadic symbionts whose abundance varied widely across individual holobionts of the same species. Identification of these two symbiont communities supports the holobiont model and calls into question the hologenome theory of evolution. PMID:26555246

  5. Basal Cell Carcinoma

    Science.gov (United States)

    ... Kids’ zone Video library Find a dermatologist Basal cell carcinoma Overview Basal cell carcinoma: This skin cancer ... that has received years of sun exposure. Basal cell carcinoma: Overview Basal cell carcinoma (BCC) is the ...

  6. Molecular characteristics of mismatch repair genes in sporadic colorectal tumors in Czech patients.

    Science.gov (United States)

    Vymetalkova, Veronika Polakova; Slyskova, Jana; Korenkova, Vlasta; Bielik, Ludovit; Langerova, Lucie; Prochazka, Pavel; Rejhova, Alexandra; Schwarzova, Lucie; Pardini, Barbara; Naccarati, Alessio; Vodicka, Pavel

    2014-01-31

    Mismatch repair (MMR) genes are known to be frequently altered in colorectal cancer (CRC). Both genetics and epigenetics modifications seems to be relevant in this phenomenon, however it is still not clear how these two aspects are interconnected. The present study aimed at characterizing of epigenetic and gene expression profiles of MMR genes in sporadic CRC patients from the Czech Republic, a country with one of the highest incidences of this cancer all over Europe. Expression levels and CpG promoter methylation status of all MMR genes were evaluated in DNA from tumor and adjacent mucosal samples of 53 incident CRC patients. We have found significantly increased transcription levels in EXO1 gene in tumor tissues (P = 0.05) and significant over-expression of MSH3 gene in colon tumors when compared to adjacent mucosal tissues (P = 0.02). Interestingly, almost all MMR genes were differently expressed when localization of tumors was compared. In particular, colon tumors showed an up-regulation of EXO1, MSH2, MSH3, MSH6, and PMS2 genes in comparison to rectal tumors (P = 0.02). Expression levels of all MMR genes positively correlated between each other. The promoter methylation of MLH1 gene was observed in 9% of CRC tissues only. In our study, we have observed different pattern of MMR genes expression according to tumor localization. However, a lack of association between methylation in MMR genes and their corresponding expressions was noticed in this study, the relationship between these two aspects is worthy to be analyzed in larger population studies and in pre-malignant stages.

  7. Infrequent detection of germline allele-specific expression of TGFBR1 in lymphoblasts and tissues of colon cancer patients.

    LENUS (Irish Health Repository)

    Guda, Kishore

    2009-06-15

    Recently, germline allele-specific expression (ASE) of the gene encoding for transforming growth factor-beta type I receptor (TGFBR1) has been proposed to be a major risk factor for cancer predisposition in the colon. Germline ASE results in a lowered expression of one of the TGFBR1 alleles (>1.5-fold), and was shown to occur in approximately 20% of informative familial and sporadic colorectal cancer (CRC) cases. In the present study, using the highly quantitative pyrosequencing technique, we estimated the frequency of ASE in TGFBR1 in a cohort of affected individuals from familial clusters of advanced colon neoplasias (cancers and adenomas with high-grade dysplasia), and also from a cohort of individuals with sporadic CRCs. Cases were considered positive for the presence of ASE if demonstrating an allelic expression ratio <0.67 or >1.5. Using RNA derived from lymphoblastoid cell lines, we find that of 46 informative Caucasian advanced colon neoplasia cases with a family history, only 2 individuals display a modest ASE, with allelic ratios of 1.65 and 1.73, respectively. Given that ASE of TGFBR1, if present, would likely be more pronounced in the colon compared with other tissues, we additionally determined the allele ratios of TGFBR1 in the RNA derived from normal-appearing colonic mucosa of sporadic CRC cases. We, however, found no evidence of ASE in any of 44 informative sporadic cases analyzed. Taken together, we find that germline ASE of TGFBR1, as assayed in lymphoblastoid and colon epithelial cells of colon cancer patients, is a relatively rare event.

  8. Distinct molecular patterns based on proximal and distal sporadic colorectal cancer: arguments for different mechanisms in the tumorigenesis.

    Science.gov (United States)

    Azzoni, Cinzia; Bottarelli, Lorena; Campanini, Nicoletta; Di Cola, Gabriella; Bader, Giovanni; Mazzeo, Antonio; Salvemini, Carlo; Morari, Silvia; Di Mauro, Davide; Donadei, Enrico; Roncoroni, Luigi; Bordi, Cesare; Sarli, Leopoldo

    2007-02-01

    Colorectal cancer (CRC) ranks as the fourth most frequently diagnosed cancer worldwide. CRCs that arise proximally or distally to the splenic flexure show differences in epidemiologic incidence, morphology, and molecular alterations, suggesting the existence of two categories of CRC based on the site of origin. The aim of the present work is to investigate the histological and molecular differences between CRCs located proximally and distally to the splenic flexure, and their potential involvement in tumor prognosis and therapeutic strategies. We evaluated 120 patients affected by sporadic CRC for clinicopathologic features, microsatellite instability (MSI), loss of heterozygosity (LOH) of chromosomes 18q, 8p, and 4p; they were also investigated for hMlh1, hMsh2, Fhit, p27, and Cox-2 immunostaining. The mucinous histotype was more frequent in the proximal than in the distal CRCs (pcancer development between the proximal and the distal colon, with potential implications in the therapeutic approach.

  9. Sporadic Hirschsprung`s disease due to a novel nonsense mutation in the RET protooncogene

    Energy Technology Data Exchange (ETDEWEB)

    Carlson, K.M.; Donis-Keller, H.; Langer, J.C. [and others

    1994-09-01

    Hirschsprung`s disease (HSCR, aganglionic megacolon) is characterized by a lack of ganglion cells along variable lengths of the hindgut. This is most likely due to a failure of the progenitor cells (that are destined to become the ganglion cells of the submucosal and myenteric plexuses) to complete their distal migration in the colon. Recently, mutations in the RET protoocogene have been reported in association with HSCR. We report a novel nonsense mutation resulting in a severely truncated protein. Germline DNA from a panel of 6 HSCR patients was analyzed by SSCP for 20 exons of RET. Eight exons were also directly sequenced. We identified a novel mutation within RET exon 2. The mutation (TAC{sub 36}{yields}TAG{sub 36}), which occurs at nucleotide position 108, involves the replacement of tyrosine with a stop codon and results in a truncated 35 amino acid protein. This mutation is the most 5{prime} nonsense mutation reported thus far. Interestingly, the patient has no prior family history of HSCR and was also diagnosed with multiple developmental anomalies including dysplastic kidney. Recent gene targeting studies with mouse models have shown that RET is essential for normal renal development. However, a parallel phenotype has not been seen in other reported HSCR patients with RET mutations. The observations reported here provide evidence that RET plays a role in human renal development. Ongoing studies will determine the extent of RET involvement in sporadic cases of HSCR.

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

    LENUS (Irish Health Repository)

    Canney, A

    2012-02-01

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

  11. Diverticular disease of the right colon

    Directory of Open Access Journals (Sweden)

    Boutross-Tadross Odette

    2011-10-01

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

  12. CT in colon cancer

    International Nuclear Information System (INIS)

    Fujita, Nobuyuki; Hasegawa, Takashi; Kubo, Kozo; Ogawa, Hajime; Sato, Yukihiko; Tomita, Masayoshi; Hanawa, Makoto; Matsuzawa, Tohru; Nishioka, Ken

    1990-01-01

    CT pictures from 59 lesions of advanced colon cancer including rectal cancer were reviewed to evaluate a role of CT in preoperative staging diagnosis. CT findings were recorded following general rules for clinical and pathological studies on cancer of colon rectum and anus, proposed by Japanese society for cancer of colon and rectum. Tumors were detected in 90% of advanced colon cancers. Sensitivity in local extension (S factor) was 58.0%. Sensitivity in lymphonode involvement (N factor) was 50.0%. Sensitivity in final staging diagnosis, dividing colon cancer into two groups below st II and above st III, was 63.3%. Further study should be necessitated to provide useful information for preoperative staging diagnosis of colon cancer. (author)

  13. Colon cancer screening

    Science.gov (United States)

    Screening for colon cancer; Colonoscopy - screening; Sigmoidoscopy - screening; Virtual colonoscopy - screening; Fecal immunochemical test; Stool DNA test; sDNA test; Colorectal cancer - screening; Rectal ...

  14. Traditional serrated adenomas and serrated carcinomas in carcinogen-treated rats.

    Science.gov (United States)

    Rubio, Carlos A

    2017-04-01

    A recent review of archived sections from early experiments in rats showed neoplasias exhibiting serrated configurations. The aim was to assess the frequency of serrated neoplasias in the colon and small intestine of carcinogen-treated rats. While reviewing archival sections from early experiments in Sprague-Dawley (SD) and Fisher-344 (F-344) rats, we recently detected colonic and intestinal traditional serrated adenomas (displaying serrated or microtubular patterns) and serrated carcinomas. SD rats were injected 1,2-dimethylhydrazine (DMH) for 27 weeks whereas F-344 rats were fed with a pyrolysate (GLU-1) for 24 months. Filed sections from 358 colonic and small intestinal neoplasias were re-evaluated. DMH-treated SD rats had 215 colonic neoplasias (1.4% were serrated adenomas, 7.9% microtubular adenomas, 2.8% serrated carcinomas and 2.8% microtubular carcinomas). GLU1-treated F-344 rats had 53 colonic neoplasias (1.9% were serrated adenomas and 20.8% microtubular adenomas), and 89 small intestinal neoplasias (1.1% were serrated adenomas, 42.7% microtubular adenomas and 6.7%, microtubular carcinomas). DMH/SD-rats develop serrated and microtubular adenomas and carcinomas in the colon, whereas GLU1/F-344 rats develop microtubular adenomas in the colon and microtubular adenomas and carcinomas in the small intestine. The two rat-settings emerge as suitable models to study the molecular attributes of serrated and microtubular neoplasias under the standard conditions of the laboratory. This study is the first showing that a substantial number of serrated and particularly microtubular adenomas and carcinomas develop in the colon and small intestine of experimental rats. Importantly, serrated and microtubular neoplasias in rats recreate the histology of duodenal and colonic traditional serrated neoplasias in human beings. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  15. Comparison of glycoprotein expression between ovarian and colon adenocarcinomas

    DEFF Research Database (Denmark)

    Multhaupt, H A; Arenas-Elliott, C P; Warhol, M J

    1999-01-01

    , carcinoembryonic antigen, and cytokeratins 7 and 20 to detect tumor-associated glycoproteins and keratin proteins in ovarian and colonic carcinomas. RESULTS: CA125, carcinoembryonic antigen, and cytokeratins 7 and 20 can distinguish between colonic and serous or endometrioid adenocarcinomas of the ovary in both...... primary and metastatic lesions. Mucinous ovarian adenocarcinomas differed in that they express carcinoembryonic antigen and cytokeratins 7 and 20 and weakly express CA125. The other glycoprotein antigens were equally expressed by ovarian and colonic adenocarcinomas and therefore were of no use...... in distinguishing between these 2 entities. CONCLUSION: A panel of monoclonal antibodies against cytokeratins 7 and 20 antigens, CA125, and carcinoembryonic antigen is useful in differentiating serous and endometrioid adenocarcinomas of the ovary from colonic adenocarcinomas. Mucinous ovarian adenocarcinomas cannot...

  16. Genetic alteration in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-12-01

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

  17. Application of quantitative DTI metrics in sporadic CJD

    Directory of Open Access Journals (Sweden)

    E. Caverzasi

    2014-01-01

    Full Text Available Diffusion Weighted Imaging is extremely important for the diagnosis of probable sporadic Jakob–Creutzfeldt disease, the most common human prion disease. Although visual assessment of DWI MRI is critical diagnostically, a more objective, quantifiable approach might more precisely identify the precise pattern of brain involvement. Furthermore, a quantitative, systematic tracking of MRI changes occurring over time might provide insights regarding the underlying histopathological mechanisms of human prion disease and provide information useful for clinical trials. The purposes of this study were: 1 to describe quantitatively the average cross-sectional pattern of reduced mean diffusivity, fractional anisotropy, atrophy and T1 relaxation in the gray matter (GM in sporadic Jakob–Creutzfeldt disease, 2 to study changes in mean diffusivity and atrophy over time and 3 to explore their relationship with clinical scales. Twenty-six sporadic Jakob–Creutzfeldt disease and nine control subjects had MRIs on the same scanner; seven sCJD subjects had a second scan after approximately two months. Cortical and subcortical gray matter regions were parcellated with Freesurfer. Average cortical thickness (or subcortical volume, T1-relaxiation and mean diffusivity from co-registered diffusion maps were calculated in each region for each subject. Quantitatively on cross-sectional analysis, certain brain regions were preferentially affected by reduced mean diffusivity (parietal, temporal lobes, posterior cingulate, thalamus and deep nuclei, but with relative sparing of the frontal and occipital lobes. Serial imaging, surprisingly showed that mean diffusivity did not have a linear or unidirectional reduction over time, but tended to decrease initially and then reverse and increase towards normalization. Furthermore, there was a strong correlation between worsening of patient clinical function (based on modified Barthel score and increasing mean diffusivity.

  18. Follicular carcinoma

    International Nuclear Information System (INIS)

    Shah, D.H.; Samuel, A.M.

    1999-01-01

    Follicular thyroid carcinoma (FTC) is considered as a disease of the elderly with a higher incidence in females as compared to papillary thyroid carcinoma (PTC). Some studies have reported its occurrence at an early age, which may be attributed to early diagnosis because of the availability of advanced techniques. The prognosis of the disease is considered poor as compared to that of PTC. The conclusions drawn in this review are based on 663 cases in whom adequate data was available for meaningful analysis followed for a mean period of 9.2 years, median, 7.8 years; range, 1-32 years

  19. Ameloblastic carcinoma

    Directory of Open Access Journals (Sweden)

    Praveen B Kumar

    2009-01-01

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

  20. Imaging and clinical characteristics of sporadic Creutzfeldt-Jakob disease

    Directory of Open Access Journals (Sweden)

    HAN Shun-chang

    2013-04-01

    Full Text Available Five patients with sporadic Creutzfeldt-Jakob disease (sCJD presented rapidly progressive dementia which were subacute onset from 1 to 4 months. Among these cases, periodic synchronous discharge (PSD of electroencephalography (EEG was seen in 2 patients. Besides, 4 patients obtained positive results in cerebrospinal fluid (CSF analysis for 14-3-3 protein. The cranial MRI examination showed symmetrical or asymmetrical colored-ribbon-shaped high signals in cerebral cortex or basal ganglia by diffusion weighted imaging (DWI, suggesting that DWI had high sensitivity and specificity for the diagnosis of sCJD as a preferred method in the clinical examination of sCJD.

  1. Diffusion MR imaging in sporadic Creutzfeldt-Jakob disease

    Directory of Open Access Journals (Sweden)

    Burcak Cakir Pekoz

    2014-08-01

    Full Text Available Creutzfeldt-Jakob disease (CJD is a rare dementing disease and is thought to caused by a prion. It is characterized by rapidly progressive dementia, ataxia, myoclonus, akinetic mutism and eventual death. Brain biopsy or autopsy is required for a definitive diagnosis of CJD. Diffusion-weighted imaging became an important tool for early diagnosis of CJD because of the high sensitivity. We present 59-year-old female patient diagnosed as sporadic CJD with typical MR imagings. [Cukurova Med J 2014; 39(4.000: 880-883

  2. The monster sporadic group and a theory underlying superstring models

    International Nuclear Information System (INIS)

    Chapline, G.

    1996-09-01

    The pattern of duality symmetries acting on the states of compactified superstring models reinforces an earlier suggestion that the Monster sporadic group is a hidden symmetry for superstring models. This in turn points to a supersymmetric theory of self-dual and anti-self-dual K3 manifolds joined by Dirac strings and evolving in a 13 dimensional spacetime as the fundamental theory. In addition to the usual graviton and dilaton this theory contains matter-like degrees of freedom resembling the massless states of the heterotic string, thus providing a completely geometric interpretation for ordinary matter. 25 refs

  3. Fruits, vegetables and hMLH1 protein-deficient and-proficient colon cancer: the Netherlands Cohort Study

    NARCIS (Netherlands)

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

    2005-01-01

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

  4. CT Findings of Colonic Complications Associated with Colon Cancer

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-04-15

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

  5. CT Findings of Colonic Complications Associated with Colon Cancer

    International Nuclear Information System (INIS)

    Kim, Sang Won; Shin, Hyeong Cheol; Kim, Il Young; Kim, Young Tong; Kim, Chang Jin

    2010-01-01

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

  6. Colon and rectal cancer

    International Nuclear Information System (INIS)

    Saldombide, L.; Cordoba, A.

    2010-01-01

    This study is about the diagnosis, therapy and monitoring of colon cancer. The techniques used are the endoscopy with biopsy in the pre and post operative colon surgery, abdominal ultrasound, chest X-ray studies of hemogram as well as liver and renal function

  7. Colon cancer - slideshow

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/presentations/100157.htm Colon cancer - Series—Normal anatomy To use the sharing features on this page, please enable JavaScript. Go to slide 1 out of 5 Go to slide 2 out of ... to slide 5 out of 5 Overview The colon, or large intestine, is a muscular tube that ...

  8. Colon of the rat

    International Nuclear Information System (INIS)

    Lindstroem, C.G.; Rosengren, J.-E.; Fork, F.-T.

    1979-01-01

    The anatomy and radiologic appearance of the colon in rats are described on the basis of 300 animals treated with carcinogenic agents and 40 normal rats. The macroscopic and microscopic appearance of the mucosa varies in the different parts of the colon. Lymphoid plaques are normal structures. The results justify a new anatomic nomenclature. (Auth.)

  9. Understanding your colon cancer risk

    Science.gov (United States)

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

  10. Parathyroid carcinoma

    DEFF Research Database (Denmark)

    Qvist, N; Krøll, L; Ladefoged, C

    1986-01-01

    Parathyroid carcinoma is a slow growing tumor, and the patients most often die from complications to the hypercalcemia. Therefore, any attempt should be made to remove local recurrence and metastasis surgically, as medical treatment is disappointing. A case treated with extensive vascular surgery...

  11. Nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Brennan Bernadette

    2006-06-01

    Full Text Available Abstract Nasopharyngeal carcinoma (NPC is a tumor arising from the epithelial cells that cover the surface and line the nasopharynx. The annual incidence of NPC in the UK is 0.3 per million at age 0–14 years, and 1 to 2 per million at age 15–19 years. Incidence is higher in the Chinese and Tunisian populations. Although rare, NPC accounts for about one third of childhood nasopharyngeal neoplasms. Three subtypes of NPC are recognized in the World Health Organization (WHO classification: 1 squamous cell carcinoma, typically found in the older adult population; 2 non-keratinizing carcinoma; 3 undifferentiated carcinoma. The tumor can extend within or out of the nasopharynx to the other lateral wall and/or posterosuperiorly to the base of the skull or the palate, nasal cavity or oropharynx. It then typically metastases to cervical lymph nodes. Cervical lymphadenopathy is the initial presentation in many patients, and the diagnosis of NPC is often made by lymph node biopsy. Symptoms related to the primary tumor include trismus, pain, otitis media, nasal regurgitation due to paresis of the soft palate, hearing loss and cranial nerve palsies. Larger growths may produce nasal obstruction or bleeding and a "nasal twang". Etiological factors include Epstein-Barr virus (EBV, genetic susceptibility and consumption of food with possible carcinogens – volatile nitrosamines. The recommended treatment schedule consists of three courses of neoadjuvant chemotherapy, irradiation, and adjuvant interferon (IFN-beta therapy.

  12. Carcinoma vulvar

    Directory of Open Access Journals (Sweden)

    Yamit Peñas Zayas

    2015-11-01

    Full Text Available El carcinoma de la vulva tiene una incidencia de aproximadamente un 3-5% dentro de todas las enfermedades ginecológicas malignas. El 90% de los tumores malignos de la vulva está constituido por carcinoma epidermoide, el resto son adenocarcinomas, carcinomas de células basales y melanomas. Se realiza la presentación de un caso de una paciente femenina de 25 años de edad con antecedentes  de Diabetes Mellitus tipo II y trombopatia, que ingresa en el servicio de ginecología con un cuadro cutáneo polimorfo, localizado en labios mayores y menores, dado por lesiones eritematoerosivas y vegetante, sospechándose clínicamente el diagnóstico  de un carcinoma epidermoide, corroborándose el mismo histológicamente al realizarse biopsia de piel. Se indicó tratamiento con quimioterapia. Por la edad de la paciente y ser menos frecuente en mucosa que en la piel,  motivo la presentación del caso.

  13. An Act of Colonization

    DEFF Research Database (Denmark)

    Rasmussen, Anders Bo

    When Gideon Welles, U.S. Secretary of the Navy, sat down to write his diary entry on September 26, 1862, his thoughts turned once more to colonization. President Lincoln was an ardent proponent of colonization, “the government-promoted settlement of black Americans in Africa or some other location....... Croix. Thus, when the Lincoln administration seriously considered colonization plans in 1862, Danish Charge d’Affaires Waldemar Raasløff offered free transport for freedmen to the Caribbean island, where there was a “distinct lack of laborers.” As a small first step towards colonization, Denmark...... in the island of St. Croix,” and the Lincoln administration’s continued exploration of colonization arrangements in subsequent years, no further negotiations were carried out at that time and no laborers in American custody were shipped to St. Croix. This paper attempts to answer why....

  14. Slower Dynamics and Aged Mitochondria in Sporadic Alzheimer's Disease

    Science.gov (United States)

    Gargini, Ricardo; García, Esther; Perry, George

    2017-01-01

    Sporadic Alzheimer's disease corresponds to 95% of cases whose origin is multifactorial and elusive. Mitochondrial dysfunction is a major feature of Alzheimer's pathology, which might be one of the early events that trigger downstream principal events. Here, we show that multiple genes that control mitochondrial homeostasis, including fission and fusion, are downregulated in Alzheimer's patients. Additionally, we demonstrate that some of these dysregulations, such as diminished DLP1 levels and its mitochondrial localization, as well as reduced STOML2 and MFN2 fusion protein levels, take place in fibroblasts from sporadic Alzheimer's disease patients. The analysis of mitochondrial network disruption using CCCP indicates that the patients' fibroblasts exhibit slower dynamics and mitochondrial membrane potential recovery. These defects lead to strong accumulation of aged mitochondria in Alzheimer's fibroblasts. Accordingly, the analysis of autophagy and mitophagy involved genes in the patients demonstrates a downregulation indicating that the recycling mechanism of these aged mitochondria might be impaired. Our data reinforce the idea that mitochondrial dysfunction is one of the key early events of the disease intimately related with aging. PMID:29201274

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

    Directory of Open Access Journals (Sweden)

    Mai Phuong L

    2007-03-01

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

  16. [Hydrocolonic sonography--potentials and limitations of ultrasonographic diagnosis of colon diseases].

    Science.gov (United States)

    Limberg, B

    2001-12-01

    Hydrocolonic sonography - potentials and limitations of ultrasonographic diagnosis of colon diseases. Ultrasonic examination has become increasingly important in the diagnosis of diseases of the gastrointestinal tract. In neoplastic diseases of the large intestine, however, the diagnostic value of conventional transabdominal sonography is limited. The sonographic evaluation of the colon could be improved by the retrograde instillation of water into the colon in a procedure called hydrocolonic sonography. This technique allows the visualization of the colon sonographically from the rectosigmoid transition to the cecum. Hydrocolonic sonography enables a detailed sonographic examination of the hypoechoic colonic lumen, the five individual layers of the colon wall and the surrounding connective tissue, thus providing additional information and allowing a more precise diagnosis of many diseases of the colon. Colonic polyps and carcinomas appear sonographically as echogenic structures projecting from the intestinal wall into the lumen. Colonic polyps larger than 7 mm in diameter and carcinomas of the colon can be detected with great sensitivity. In addition, detailed evaluation of the structure of the bowel wall permits more precise staging of tumors of the colon. Aside from such localized changes, hydrocolonic sonography can also demonstrate changes in the wall structure in chronic inflammatory large bowel diseases such as Crohn's disease and ulcerative colitis. In addition hydrocolonic sonography has been proven to be of great value for the ultrasonographically-guided hydrostatic reduction of intussusception in children. On the other hand virtual colonoscopy is another promising new imaging method for the diagnosis of colon diseases. The differences between hydrcolonic sonography and virtual colonoscopy and their potential for screening purposes of colon cancer will be discussed.

  17. Inadequate preoperative colonic evaluation for synchronous colorectal cancer

    DEFF Research Database (Denmark)

    Achiam, M P; Burgdorf, S K; Wilhelmsen, M

    2009-01-01

    BACKGROUND AND AIMS: Synchronous cancers (SC) are well known (2-11%) in patients with colorectal carcinoma (CRC). One study has shown that intraoperative palpation can miss up to 69% of the SC while other studies have shown altered planned surgical procedure due to preoperatively diagnosed...... in our department were reviewed. Only patients with CRC were included. Information regarding pre-, per- and postoperative colonic evaluation were obtained and occurrences of SC were evaluated. RESULTS: Of the 534 patients included 124 (23%) patients had an impassable stenosis. Full preoperative colonic...

  18. Molecular profile of ductal carcinoma in situ of the breast in BRCA1 and BRCA2 germline mutation carriers

    NARCIS (Netherlands)

    van der Groep, P.; van Diest, P. J.; Menko, F. H.; Bart, J.; de Vries, E. G. E.; van der Wall, E.

    2009-01-01

    Aims: Ductal carcinoma in situ (DCIS) is an established late precursor of sporadic invasive breast cancer and to a large extent parallels its invasive counterpart with respect to molecular changes and immunophenotype. Invasive breast cancers in germline BRCA1 and BRCA2 mutation carriers have a

  19. Sonography in Colonic Diverticulitis

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-06-15

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

  20. Sonography in Colonic Diverticulitis

    International Nuclear Information System (INIS)

    Sohn, Mi Yun; Choi, Byung Hun; Kim, Keum Won; Kwon, Kwi Ryun; Lim, Myung Ah; Kim, Sung Soo; Choi, Chang Ho

    1996-01-01

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

  1. A rare case of sporadic multiple trichoepitheliomas | Sanaa | Pan ...

    African Journals Online (AJOL)

    No other contributory medical history or similar cases in the family were reported by the patient. With the above features a clinical differential diagnosis of multiple basal cell carcinoma (BCC), multiples trichoepitheliomas or Bourneville's tuberous sclerosis was considered. Histopathological examination of the lesions was in ...

  2. Aberrant gene promoter methylation associated with sporadic multiple colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Victoria Gonzalo

    Full Text Available BACKGROUND: Colorectal cancer (CRC multiplicity has been mainly related to polyposis and non-polyposis hereditary syndromes. In sporadic CRC, aberrant gene promoter methylation has been shown to play a key role in carcinogenesis, although little is known about its involvement in multiplicity. To assess the effect of methylation in tumor multiplicity in sporadic CRC, hypermethylation of key tumor suppressor genes was evaluated in patients with both multiple and solitary tumors, as a proof-of-concept of an underlying epigenetic defect. METHODOLOGY/PRINCIPAL FINDINGS: We examined a total of 47 synchronous/metachronous primary CRC from 41 patients, and 41 gender, age (5-year intervals and tumor location-paired patients with solitary tumors. Exclusion criteria were polyposis syndromes, Lynch syndrome and inflammatory bowel disease. DNA methylation at the promoter region of the MGMT, CDKN2A, SFRP1, TMEFF2, HS3ST2 (3OST2, RASSF1A and GATA4 genes was evaluated by quantitative methylation specific PCR in both tumor and corresponding normal appearing colorectal mucosa samples. Overall, patients with multiple lesions exhibited a higher degree of methylation in tumor samples than those with solitary tumors regarding all evaluated genes. After adjusting for age and gender, binomial logistic regression analysis identified methylation of MGMT2 (OR, 1.48; 95% CI, 1.10 to 1.97; p = 0.008 and RASSF1A (OR, 2.04; 95% CI, 1.01 to 4.13; p = 0.047 as variables independently associated with tumor multiplicity, being the risk related to methylation of any of these two genes 4.57 (95% CI, 1.53 to 13.61; p = 0.006. Moreover, in six patients in whom both tumors were available, we found a correlation in the methylation levels of MGMT2 (r = 0.64, p = 0.17, SFRP1 (r = 0.83, 0.06, HPP1 (r = 0.64, p = 0.17, 3OST2 (r = 0.83, p = 0.06 and GATA4 (r = 0.6, p = 0.24. Methylation in normal appearing colorectal mucosa from patients with multiple and solitary CRC showed no relevant

  3. Papillary carcinoma

    International Nuclear Information System (INIS)

    Shah, D.H.; Samuel, A.M.

    1999-01-01

    Papillary carcinoma of the thyroid (PTC) constitutes a major proportion of all thyroid cancers and is generally believed to be a slow growing tumor with an indolent course. The diagnosis of PTC often makes the physician overly optimistic and complacent and yet this tumor can be aggressive in a subset of patients leading to death in a few months. The fundamental but subtle differences underlying the extremes in biologic behaviour of this complex and fascinating tumor remain poorly understood. Although there is a general agreement among the investigators regarding prognostic factors, controversy exists about the management of the disease. There is divided opinion with respect to the type and extent of surgery and the need for radioiodine (1 31 I) treatment in case of PTC. The experiences at Radiation Medicine Centre (RMC) of 1904 cases of differentiated thyroid carcinoma (DTC) registered during the period 1963-1990 are reviewed

  4. Thyroid carcinoma

    International Nuclear Information System (INIS)

    Lambertini, Roberto; Dalurzo, Liliana; Jaen, Ana del V.

    2008-01-01

    In this document the case of a 66-year old woman is presented, with record of multi nodular goiter of 5 year of evolution, which is derived to scan ultrasound office to make a puncture-aspiration with thin needle because of the growth of nodular thyroid injuries. The ultrasound scan examination made before the puncture determine multiple dominant nodules of hyperplasia aspect between 15 and 25 mm of diameter and a small nodule of 6 mm suspected proliferate process. Despite its size, it was decided to include small nodule in injuries to a biopsy. The cytological study reveals nodular hyperplasia with carcinoma in the small nodule of 6 mm. A thyroidectomy is practiced on the patient. The deferred histological study of the thyroid gland confirms the finding of multi-nodular goiter with a small focus of papillar carcinoma. The ganglions examined were negative in the deferred examination [es

  5. Unusual metachronous isolated inguinal lymph node metastasis from adenocarcinoma of the sigmoid colon

    Directory of Open Access Journals (Sweden)

    Parodo Giuseppina

    2011-10-01

    Full Text Available Abstract This study aimed to describe an unusual case of metachronous isolated inguinal lymph nodes metastasis from sigmoid carcinoma. A 62-year-old man was referred to our department because of an obstructing sigmoid carcinoma. Colonoscopy showed the obstructing lesion at 30 cm from the anal verge and abdominal CT revealed a sigmoid lesion infiltrating the left lateral abdominal wall. The patient underwent a colonic resection extended to the abdominal wall. Histology showed an adenocarcinoma of the colon infiltrating the abdominal wall with iuxtacolic nodal involvement. Thirty three months after surgery abdominal CT and PET scan revealed a metastatic left inguinal lymph node involvement. The metastatic lymph node was found strictly adherent to the left iliac-femoral artery and encompassing the origin of the left inferior epigastric artery. Histology showed a metachronous nodal metastasis from colonic adenocarcinoma. Despite metastastic involvement of inguinal lymph node from rectal cancer is a rare but well known clinical entity, to the best of our knowledge, this is the first report of inguinal metastasis from a carcinoma of the left colon. Literature review shows only three other similar reported cases: two cases of inguinal metastasis secondary to adenocarcinoma of the cecum and one case of axillary metastasis from left colonic carcinoma. A metastatic pathway through superficial abdominal wall lymphatic vessels could be possible through the route along the left inferior epigastric artery. The solitary inguinal nodal involvement from rectal carcinoma could have a more favorable prognosis. In the case of nodal metastasis to the body surface lymph nodes from colonic carcinoma, following the small number of such cases reported in the literature, no definitive conclusions can be drawn.

  6. Understanding Antegrade Colonic Enema (ACE) Surgery

    Science.gov (United States)

    ... Colonic Enema (ACE) Surgery Antegrade Colonic Enema (ACE) Surgery Antegrade colonic enema surgery (ACE) is a procedure ... Risks / Benefits What is antegrade colonic enema (ACE) surgery? Antegrade colonic enema surgery (ACE) or Malone antegrade ...

  7. A Unifying Hypothesis for Familial and Sporadic Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Carole J. Proctor

    2012-01-01

    Full Text Available Alzheimer's disease (AD is characterised by the aggregation of two quite different proteins, namely, amyloid-beta (Aβ, which forms extracellular plaques, and tau, the main component of cytoplasmic neurofibrillary tangles. The amyloid hypothesis proposes that Aβ plaques precede tangle formation but there is still much controversy concerning the order of events and the linkage between Aβ and tau alterations is still unknown. Mathematical modelling has become an essential tool for generating and evaluating hypotheses involving complex systems. We have therefore used this approach to discover the most probable pathway linking Aβ and tau. The model supports a complex pathway linking Aβ and tau via GSK3β, p53, and oxidative stress. Importantly, the pathway contains a cycle with multiple points of entry. It is this property of the pathway which enables the model to be consistent with both the amyloid hypothesis for familial AD and a more complex pathway for sporadic forms.

  8. Physical function and muscle strength in sporadic inclusion body myositis

    DEFF Research Database (Denmark)

    Jørgensen, Anders N; Aagaard, Per; Nielsen, Jakob L

    2017-01-01

    INTRODUCTION: In this study, self-reported physical function, functional capacity, and isolated muscle function were investigated in sporadic inclusion body myositis (sIBM) patients. METHODS: The 36-item Short Form (SF-36) Health Survey and 2-min walk test (2MWT), timed up & go test (TUG), and 30-s...... chair stand performance were evaluated. In addition, patients were tested for knee extensor muscle strength (isokinetic dynamometer) and leg extension power (Nottingham power rig). RESULTS: TUG performance was the strongest predictor of self-reported physical function (r(2) = 0.56, P ... to sensitively predict self-perceived physical function in sIBM patients. Notably, between-limb asymmetry in lower limb muscle strength had a substantial negative impact on motor tasks involving gait function. Muscle Nerve, 2017....

  9. Sporadic Insulinoma Presenting as Early Morning Night Terrors.

    Science.gov (United States)

    Beisang, Daniel; Forlenza, Gregory P; Luquette, Mark; Sarafoglou, Kyriakie

    2017-06-01

    A 16-year-old boy with a recent diagnosis of night terrors was evaluated for recurrent early morning hypoglycemia after an early morning seizure. Evaluation in clinic with critical laboratories identified hyperinsulinemic hypoglycemia. Additional investigation revealed a sporadic insulinoma as the etiology of his hypoglycemia and all symptoms were resolved after pancreaticoduodenectomy. The importance of obtaining critical laboratory samples is highlighted and appropriate radiologic, medical, and pathologic testing is discussed. We additionally review the medical and surgical management of hyperinsulinemic hypoglycemia. A discussion of multiple endocrine neoplasia type 1 associated insulinomas is included as well. This case highlights the importance of considering hypoglycemia in the evaluation of night terrors and new-onset seizures. Copyright © 2017 by the American Academy of Pediatrics.

  10. Cathepsin D polymorphism in Italian sporadic and familial Alzheimer's disease.

    Science.gov (United States)

    Bagnoli, Silvia; Nacmias, Benedetta; Tedde, Andrea; Guarnieri, Bianca Maria; Cellini, Elena; Ciantelli, Monica; Petruzzi, Concetta; Bartoli, Antonella; Ortenzi, Luigi; Serio, Antonio; Sorbi, Sandro

    2002-08-16

    A recent study has shown that a genetic variation in the Cathepsin D (catD) gene is a major risk factor for the development of Alzheimer's disease (AD). CatD is an intracellular aspartyl protease involved in neurodegeneration. A C-->T (Ala-->Val) transition at position 224 has been associated with altered intracellular maturation. Recently, a significant overrepresentation of the T allele of the catD gene in AD patients compared with controls was reported. However, this finding has not yet been confirmed. We analyzed the distribution of catD and apolipoprotein E polymorphisms in Italian patients with sporadic and familial AD (FAD). Our studies revealed that the distribution of catD polymorphism did not differ in AD and FAD patients and controls. Thus, our data do not support a role for the catD gene as a genetic risk factor in the development of AD.

  11. Inactivation of JNK2 as carcinogenic factor in colitis-associated and sporadic colorectal carcinogenesis.

    Science.gov (United States)

    Lessel, Wiebke; Silver, Andrew; Jechorek, Doerthe; Guenther, Thomas; Roehl, Friedrich-Wilhelm; Kalinski, Thomas; Roessner, Albert; Poehlmann-Nitsche, Angela

    2017-05-01

    We recently reported that dysregulated c-Jun N-terminal kinases (JNK) activity causes defective cell cycle checkpoint control, inducing neoplastic transformation in a cellular ulcerative colitis (UC) model. In the quiescent chronic phase of UC, p-p54 JNK was down-regulated and p-p46 JNK was up-regulated. Both were up-regulated in the acute phase. Consequently, increased p21WAF1 and γ-H2AX, two JNK-regulated proteins, induced cell cycle arrest. Their down-regulation led to checkpoint override, causing increased proliferation and undetected DNA damage in quiescent chronic phase, all characteristics of tumorigenesis. We investigated expression of p-JNK2, p-JNK1-3, p21WAF1, γ-H2AX and Ki67 by immunohistochemistry in cases of quiescent UC (QUC), active UC (AUC), UC-dysplasia and UC-related colorectal carcinoma (UC-CRC). Comparison was made to normal healthy colorectal mucosa, sporadic adenoma and colorectal carcinoma (CRC), diverticulitis and Crohns disease (CD). We found p-JNK2 up-regulation in AUC and its early down-regulation in UC-CRC and CRC carcinogenesis. With down-regulated p-JNK2, p21WAF1 was also decreased. Ki67 was inversely expressed, showing increased proliferation early in UC-CRC and CRC carcinogenesis. p-JNK1-3 was increased in AUC and QUC. Less increased γ-H2AX in UC-CRC compared to CRC gave evidence that colitis-triggered inflammation masks DNA damage, thus contributing to neoplastic transformation. We hypothesize that JNK-dependent cell cycle arrest is important in AUC, while chronic inflammation causes dysregulated JNK activity in quiescent phase that may contribute to checkpoint override, promoting UC carcinogenesis. We suggest restoring p-JNK2 expression as a novel therapeutic strategy to early prevent the development of UC-related cancer. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. Epidemiologia do carcinoma basocelular Epidemiology of basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Valquiria Pessoa Chinem

    2011-04-01

    associated with its cause. However, other elements of risk are described, such as light skin phototypes, advanced age, family history of skin carcinoma, light eyes and blond hair, freckles in childhood and immunosuppression. Behavioral aspects such as occupational sun exposure, rural labor and sunburns at a young age also play a role. Between 30% and 75% of the sporadic cases are associated with patched hedgehog gene mutation, but other genetic changes are also described. The tumor is commonly found in concomitance with skin lesions related to chronic sun exposure, such as actinic keratoses, solar lentigines and facial telangiectasia. The prevention of basal cell carcinoma is based on the knowledge of risk factors, early diagnosis and treatment, as well as on the adoption of specific measures, particularly in susceptible populations. The authors present a review of the epidemiology of basal cell carcinoma.

  13. A Case of Sigmoid Colon Tuberculosis Mimicking Colon Cancer

    OpenAIRE

    Yu, Seong-Min; Park, Jong-Hwan; Kim, Min-Dae; Lee, Hee-Ryong; Jung, Peel; Ryu, Tae-Hyun; Choi, Seung-Ho; Lee, Il-Seon

    2012-01-01

    Tuberculosis of the sigmoid colon is a rare disorder. An 80-year-old man visited Bongseng Memorial Hospital for medical examination. A colonoscopy was performed, and a lesion in the sigmoid colon that was suspected to be colon cancer was found. A biopsy was performed, and tuberculous enteritis with chronic granulomatous inflammation was diagnosed. Intestinal tuberculosis is most frequent in the ileocecal area, followed by the ascending colon, transverse colon, duodenum, stomach, and sigmoid c...

  14. Studies on recurrence of colorectal carcinoma

    International Nuclear Information System (INIS)

    Kobayashi, Masayuki; Nosaki, Tadaharu; Murai, Tomoya; Ooshita, Ikuo; Kobayashi, Suzuo

    1989-01-01

    Recurrence patterns of colorectal carcinoma were studied in 402 patients followed up for 5 years or more after surgery. Recurrence was observed in 23% for colon cancer and 38% for rectal canccer. The most frequent site of recurrence or relapse in cases of colon cancer was the liver, followed by multiple organs and a local region; and in the case of rectal cancer, it was multiple organs, followed by a local region, the liver, lung, and bone. The rate of recurrence or relapse tended to be higher in patients with lymph node metastases or more advanced clinical stage. Liver relapse was seen in 13% for colon cancer and 12% for rectal cancer, occurring within 48 months after surgery. Since CT can detect liver relapse within 24 months, abdominal CT and chest plain roentgenography should be performed in the first 6 months, 12 months, and 24 months after surgery. (Namekawa, K)

  15. Stages of Colon Cancer

    Science.gov (United States)

    ... types of surgery : Local excision or simple polypectomy . Resection and anastomosis . This is done when the tumor is too ... stage I colon cancer usually includes the following: Resection and anastomosis . Use our clinical trial search to find NCI- ...

  16. Colonic potassium handling

    DEFF Research Database (Denmark)

    Sørensen, Mads Vaarby; Matos, Joana E.; Prætorius, Helle

    2010-01-01

    regulated by hormones and adapts readily to changes in dietary K+ intake, aldosterone and multiple local paracrine agonists. In chronic renal insufficiency, colonic K+ secretion is greatly enhanced and becomes an important accessory K+ excretory pathway. During severe diarrheal diseases of different causes......, intestinal K+ losses caused by activated ion secretion may become life threatening. This topical review provides an update of the molecular mechanisms and the regulation of mammalian colonic K+ absorption and secretion. It is motivated by recent results, which have identified the K+ secretory ion channel...... in the apical membrane of distal colonic enterocytes. The directed focus therefore covers the role of the apical Ca2+ and cAMP-activated BK channel (KCa1.1) as the apparently only secretory K+ channel in the distal colon....

  17. Colonic serrated pathway lesions: Molecular and histologic changes in serrated colonic proliferations (Review).

    Science.gov (United States)

    Fogt, Franz; Rahemtulla, Amir; Jian, Bo

    2008-01-01

    Serrated polyps of the intestinal tract, specifically those within the colon, represent a wide variety of benign and neoplastic changes. Diagnostic entities include benign hyperplastic changes in prolapse, hyperplastic polyps (HPs), serrated adenomas (SAs) and carcinomas with serrated morphology. Recent developments in molecular pathology have confirmed the existence of additional neoplastic growths, with potentially aggressive behavior, called sessile serrated adenomas (SSAs). It is important to be aware of the distinct aspects of clinical significance and the varying outcomes associated with different serrated changes. In this article, important histologic diagnoses with serrated histology are reviewed and juxtaposed, where applicable, with their respective molecular pathways.

  18. [ADRENOCORTICAL CARCINOMA].

    Science.gov (United States)

    Kranjčević, K

    2016-12-01

    Adrenocortical carcinoma is a rare entity. However, it is the most common type of cancerous adrenal gland tumor with poor prognosis. Approximately 4 to 12 per 1 million people develop this type of tumor, which begins in the adrenal cortex. Adrenocortical carcinoma can occur at any age. Women tend to be diagnosed slightly more often than men. In most cases, the cause of cancerous adrenal gland tumor remains unknown. However, people with certain hereditary conditions have a higher risk. Adrenocortical carcinoma can be a functional or nonfunctional tumor. If the tumor is functional, it may produce hormones causing symptoms such as high blood pressure, low potassium level, heart palpitations, nervousness, feelings of anxiety or panic attacks, excessive perspiration, diabetes, Cushing syndrome, unexplained weight gain or weight loss, weakness, abdominal stretch marks, excessive hair growth, changes in genitalia, change in libido, etc. If the tumor is nonfunctional, symptoms occur because the tumor has grown so large that it exerts pressure on the nearby organs, causing abdominal pain or a feeling of fullness. To diagnose adrenocortical carcinoma, in addition to thorough physical examination, the following tests are used: blood and urine tests to help determine whether the tumor is functional or nonfunctional, and imaging tests (computed tomography scan or magnetic resonance imaging). The treatment depends on cancer stage. Two major staging systems are used: the American Joint Committee on Cancer (AJCC) TNM staging system and the ENSAT (European Network for the Study of Adrenal Tumors) staging system. Both are based on the same TNM categories. The main types of treatment for adrenal cancer are surgery (the main treatment), chemotherapy and targeted therapy. Radiation therapy is not used often as the main initial treatment for adrenal cancer because the cancer cells are not easy to kill with x-rays. Radiation may be used as adjuvant therapy. By definition, adrenal

  19. Smoothened antagonist GDC-0449 (Vismodegib) inhibits proliferation and triggers apoptosis in colon cancer cell lines

    OpenAIRE

    Wu, Chuanqing; Hu, Shaobo; Cheng, Ji; Wang, Guobin; Tao, Kaixiong

    2017-01-01

    The sonic hedgehog (Shh) pathway has been proven to be involved in embryonic development and cancer growth. GDC-0449, an antagonist of the hedgehog signaling receptor Smoothened (Smo), was recently approved by the US Food and Drug Administration as a prescription for skin basal cell carcinoma. However, the efficacy of GDC-0449 in the treatment of colon cancer and other malignancies, such as basal cell carcinoma and pancreatic cancer, has remained to be proven. The present study assessed the e...

  20. Colon Cryptogenesis: Asymmetric Budding

    Science.gov (United States)

    Tan, Chin Wee; Hirokawa, Yumiko; Gardiner, Bruce S.; Smith, David W.; Burgess, Antony W.

    2013-01-01

    The process of crypt formation and the roles of Wnt and cell-cell adhesion signaling in cryptogenesis are not well described; but are important to the understanding of both normal and cancer colon crypt biology. A quantitative 3D-microscopy and image analysis technique is used to study the frequency, morphology and molecular topography associated with crypt formation. Measurements along the colon reveal the details of crypt formation and some key underlying biochemical signals regulating normal colon biology. Our measurements revealed an asymmetrical crypt budding process, contrary to the previously reported symmetrical fission of crypts. 3D immunofluorescence analyses reveals heterogeneity in the subcellular distribution of E-cadherin and β-catenin in distinct crypt populations. This heterogeneity was also found in asymmetrical budding crypts. Singular crypt formation (i.e. no multiple new crypts forming from one parent crypt) were observed in crypts isolated from the normal colon mucosa, suggestive of a singular constraint mechanism to prevent aberrant crypt production. The technique presented improves our understanding of cryptogenesis and suggests that excess colon crypt formation occurs when Wnt signaling is perturbed (e.g. by truncation of adenomatous polyposis coli, APC protein) in most colon cancers. PMID:24205248

  1. Colon cryptogenesis: asymmetric budding.

    Directory of Open Access Journals (Sweden)

    Chin Wee Tan

    Full Text Available The process of crypt formation and the roles of Wnt and cell-cell adhesion signaling in cryptogenesis are not well described; but are important to the understanding of both normal and cancer colon crypt biology. A quantitative 3D-microscopy and image analysis technique is used to study the frequency, morphology and molecular topography associated with crypt formation. Measurements along the colon reveal the details of crypt formation and some key underlying biochemical signals regulating normal colon biology. Our measurements revealed an asymmetrical crypt budding process, contrary to the previously reported symmetrical fission of crypts. 3D immunofluorescence analyses reveals heterogeneity in the subcellular distribution of E-cadherin and β-catenin in distinct crypt populations. This heterogeneity was also found in asymmetrical budding crypts. Singular crypt formation (i.e. no multiple new crypts forming from one parent crypt were observed in crypts isolated from the normal colon mucosa, suggestive of a singular constraint mechanism to prevent aberrant crypt production. The technique presented improves our understanding of cryptogenesis and suggests that excess colon crypt formation occurs when Wnt signaling is perturbed (e.g. by truncation of adenomatous polyposis coli, APC protein in most colon cancers.

  2. Secondary effects induced by the colon carcinogen azoxymethane in BDIX rats

    DEFF Research Database (Denmark)

    Kobaek-Larsen, Morten; Fenger, Claus; Ritskes-Hoitinga, Jelmera

    2004-01-01

    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...... 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....

  3. Microcystic Variant of Urothelial Carcinoma

    Directory of Open Access Journals (Sweden)

    Anthony Kodzo-Grey Venyo

    2013-01-01

    Full Text Available Background. Microcystic variant of urothelial carcinoma is one of the new variants of urothelial carcinoma that was added to the WHO classification in 2004. Aims. To review the literature on microcystic variant of urothelial carcinoma. Methods. Various internet search engines were used to identify reported cases of the tumour. Results. Microscopic features of the tumour include: (i Conspicuous intracellular and intercellular lumina/microcysts encompassed by malignant urothelial or squamous cells. (ii The lumina are usually empty; may contain granular eosinophilic debris, mucin, or necrotic cells. (iii The cysts may be variable in size; round, or oval, up to 2 mm; lined by urothelium which are either flattened cells or low columnar cells however, they do not contain colonic epithelium or goblet cells; are infiltrative; invade the muscularis propria; mimic cystitis cystica and cystitis glandularis; occasionally exhibit neuroendocrine differentiation. (iv Elongated and irregular branching spaces are usually seen. About 17 cases of the tumour have been reported with only 2 patients who have survived. The tumour tends to be of high-grade and high-stage. There is no consensus opinion on the best option of treatment of the tumour. Conclusions. It would prove difficult at the moment to be dogmatic regarding its prognosis but it is a highly aggressive tumour. New cases of the tumour should be reported in order to document its biological behaviour.

  4. MicroRNA-320a suppresses human colon cancer cell proliferation by directly targeting β-catenin

    International Nuclear Information System (INIS)

    Sun, Jian-Yong; Huang, Yi; Li, Ji-Peng; Zhang, Xiang; Wang, Lei; Meng, Yan-Ling; Yan, Bo; Bian, Yong-Qian; Zhao, Jing; Wang, Wei-Zhong

    2012-01-01

    Highlights: ► miR-320a is downregulated in human colorectal carcinoma. ► Overexpression of miR-320a inhibits colon cancer cell proliferation. ► β-Catenin is a direct target of miR-320a in colon cancer cells. ► miR-320a expression inversely correlates with mRNA expression of β-catenin’s target genes in human colon carcinoma. -- Abstract: Recent profile studies of microRNA (miRNA) expression have documented a deregulation of miRNA (miR-320a) in human colorectal carcinoma. However, its expression pattern and underlying mechanisms in the development and progression of colorectal carcinoma has not been elucidated clearly. Here, we performed real-time PCR to examine the expression levels of miR-320a in colon cancer cell lines and tumor tissues. And then, we investigated its biological functions in colon cancer cells by a gain of functional strategy. Further more, by the combinational approaches of bioinformatics and experimental validation, we confirmed target associations of miR-320a in colorectal carcinoma. Our results showed that miR-320a was frequently downregulated in cancer cell lines and colon cancer tissues. And we demonstrated that miR-320a restoration inhibited colon cancer cell proliferation and β-catenin, a functionally oncogenic molecule was a direct target gene of miR-320a. Finally, the data of real-time PCR showed the reciprocal relationship between miR-320a and β-catenin’s downstream genes in colon cancer tissues. These findings indicate that miR-320a suppresses the growth of colon cancer cells by directly targeting β-catenin, suggesting its application in prognosis prediction and cancer treatment.

  5. Colonic Diverticulitis in the Elderly

    OpenAIRE

    Chien-Kuo Liu; Hsi-Hsien Hsu; She-Meng Cheng

    2009-01-01

    Diverticular disease of the colon is a disease that mainly affects the elderly and presents in 50–70% of those aged 80 years or older. The most common complication is colonic diverticulitis. Eighty percent of patients who present with colonic diverticulitis are aged 50 years and older. Diagnosis and treatment of colonic diverticulitis in the elderly is more difficult and complicated owing to more comorbid conditions. Computed tomography is recommended for diagnosis when colonic diverticulitis...

  6. [Basal cell carcinoma. Molecular genetics and unusual clinical features].

    Science.gov (United States)

    Reifenberger, J

    2007-05-01

    Basal cell carcinoma is the most common human cancer. Its incidence is steadily increasing. The development of basal cell carcinoma is linked to genetic factors, including the individual skin phototype, as well as the cumulative exposure to UVB. The vast majority of basal cell carcinomas are sporadic tumors, while familial cases associated with certain hereditary syndromes are less common. At the molecular level, basal cell carcinomas are characterized by aberrant activation of sonic hedgehog signaling, usually due to mutations either in the ptch or smoh genes. In addition, about half of the cases carry mutations in the tp53 tumor suppressor gene, which are often UVB-associated C-->T transition mutations. Clinically, basal cell carcinomas may show a high degree of phenotypical variability. In particular, tumors occurring in atypical locations, showing an unusual clinical appearance, or imitating other skin diseases may cause diagnostic problems. This review article summarizes the current state of the art concerning the etiology, predisposition and molecular genetics of basal cell carcinoma. In addition, examples of unusual clinical manifestations are illustrated.

  7. Comparison of glycoprotein expression between ovarian and colon adenocarcinomas.

    Science.gov (United States)

    Multhaupt, H A; Arenas-Elliott, C P; Warhol, M J

    1999-10-01

    Tumor-associated antigens may be expressed as surface glycoproteins. These molecules undergo qualitative and quantitative modifications during cell differentiation and malignant transformation. During malignant transformation, incomplete glycosylation is common, and certain glycosylation pathways are preferred. These antigens might help distinguish between ovarian and colonic adenocarcinomas in the primary and metastatic lesions. Different cytokeratins have been proposed as relatively organ-specific antigens. We used monoclonal antibodies against T1, Tn, sialosyl-Tn, B72.3, CA125, carcinoembryonic antigen, and cytokeratins 7 and 20 to detect tumor-associated glycoproteins and keratin proteins in ovarian and colonic carcinomas. CA125, carcinoembryonic antigen, and cytokeratins 7 and 20 can distinguish between colonic and serous or endometrioid adenocarcinomas of the ovary in both primary and metastatic lesions. Mucinous ovarian adenocarcinomas differed in that they express carcinoembryonic antigen and cytokeratins 7 and 20 and weakly express CA125. The other glycoprotein antigens were equally expressed by ovarian and colonic adenocarcinomas and therefore were of no use in distinguishing between these 2 entities. A panel of monoclonal antibodies against cytokeratins 7 and 20 antigens, CA125, and carcinoembryonic antigen is useful in differentiating serous and endometrioid adenocarcinomas of the ovary from colonic adenocarcinomas. Mucinous ovarian adenocarcinomas cannot be distinguished from colonic adenocarcinomas using immunohistochemistry.

  8. Age-related loss of EGF-receptor related protein (ERRP) in the aging colon is a potential risk factor for colon cancer.

    Science.gov (United States)

    Schmelz, Eva M; Levi, Edi; Du, Jianhua; Xu, Hu; Majumdar, Adhip P N

    2004-12-01

    Although in Fischer-344 rats, aging is associated with increased activation of EGF-receptor (EGFR) in mucosa of much of the gastrointestinal tract, including the colon, regulation of this process is poorly understood. We hypothesize that loss of suppressor of EGFR may partly be responsible for this process. To test this hypothesis, we examined the expression of EGFR related protein (ERRP), a recently identified negative regulator of EGFR, in the colonic mucosa during aging and following administration of the colonic carcinogen dimethylhydrazine (DMH) that resulted in the formation of aberrant crypt foci (ACF), which are considered to be precursor of adenoma and carcinoma. In Fischer-344 rats, aging is associated with increased activation of EGFR in the colonic mucosa, as evidenced by 30-35% increase in the levels of tyrosine phosphorylated EGFR in the proximal and distal colon of aged (20-22 months old) than in young (4-6 months old) rats. In contrast, the levels of ERRP in both regions of the colon of aged rats were decreased by 50-60%, compared to their younger counterparts. Administration of DMH, which induced a greater number of ACF in the colon of aged rats than in young animals, resulted in a corresponding reduction in ERRP in the colon. These results suggest that loss of ERRP expression is a common event during aging and early stages of chemically induced colon cancer. We also suggest that loss of ERRP could be a risk factor for developing colorectal cancer in the older population.

  9. Sporadic Ca and Ca+ layers at mid-latitudes: Simultaneous observations and implications for their formation

    Directory of Open Access Journals (Sweden)

    M. Gerding

    2001-01-01

    Full Text Available We report on the observations of 188 sporadic layers of either Ca atoms and/or Ca ions that we have observed during 112 nights of lidar soundings of Ca, and 58 nights of Ca+ soundings, at Kühlungsborn, Germany (54° N, 12° E. The Ca+ soundings have been performed simultaneously and in a common volume with the Ca soundings by two separate lidars. Correlations between sporadic neutral and ionized metal layers are demonstrated through four case studies. A systematic study of the variations of occurrence of sporadic Ca and Ca+ layers reveals that neutral and ionized Ca layers are not as closely correlated as expected earlier: (a The altitude distribution shows the simultaneous occurrence of both sporadic Ca and Ca+ layers to be most likely only in the narrow altitude range between 90 and 95 km. Above that region, in the lower thermosphere, the sporadic ion layers are much more frequent than atom layers. Below 90 km only very few sporadic layers have been observed; (b The seasonal variation of sporadic Ca layers exhibits a minimum of occurrence in summer, while sporadic Ca+ layers do not show a significant seasonal variation (only the dense Ca+ layers appear to have a maximum in summer. At mid-latitudes sporadic Ca layers are more frequent than sporadic layers of other atmospheric metals like Na or K. For the explanation of our observations new formation mechanisms are discussed.Key words. Ionosphere (ion chemistry and composition; ionosphere-atmosphere interactions; mid-latitude ionosphere

  10. The Accessory Genome of Shiga Toxin-Producing Escherichia coli Defines a Persistent Colonization Type in Cattle.

    Science.gov (United States)

    Barth, Stefanie A; Menge, Christian; Eichhorn, Inga; Semmler, Torsten; Wieler, Lothar H; Pickard, Derek; Belka, Ariane; Berens, Christian; Geue, Lutz

    2016-09-01

    Shiga toxin-producing Escherichia coli (STEC) strains can colonize cattle for several months and may, thus, serve as gene reservoirs for the genesis of highly virulent zoonotic enterohemorrhagic E. coli (EHEC). Attempts to reduce the human risk for acquiring EHEC infections should include strategies to control such STEC strains persisting in cattle. We therefore aimed to identify genetic patterns associated with the STEC colonization type in the bovine host. We included 88 persistent colonizing STEC (STEC(per)) (shedding for ≥4 months) and 74 sporadically colonizing STEC (STEC(spo)) (shedding for ≤2 months) isolates from cattle and 16 bovine STEC isolates with unknown colonization types. Genoserotypes and multilocus sequence types (MLSTs) were determined, and the isolates were probed with a DNA microarray for virulence-associated genes (VAGs). All STEC(per) isolates belonged to only four genoserotypes (O26:H11, O156:H25, O165:H25, O182:H25), which formed three genetic clusters (ST21/396/1705, ST300/688, ST119). In contrast, STEC(spo) isolates were scattered among 28 genoserotypes and 30 MLSTs, with O157:H7 (ST11) and O6:H49 (ST1079) being the most prevalent. The microarray analysis identified 139 unique gene patterns that clustered with the genoserotypes and MLSTs of the strains. While the STEC(per) isolates possessed heterogeneous phylogenetic backgrounds, the accessory genome clustered these isolates together, separating them from the STEC(spo) isolates. Given the vast genetic heterogeneity of bovine STEC strains, defining the genetic patterns distinguishing STEC(per) from STEC(spo) isolates will facilitate the targeted design of new intervention strategies to counteract these zoonotic pathogens at the farm level. Ruminants, especially cattle, are sources of food-borne infections by Shiga toxin-producing Escherichia coli (STEC) in humans. Some STEC strains persist in cattle for longer periods of time, while others are detected only sporadically. Persisting

  11. Molecular and cellular pathways associated with chromosome 1p deletions during colon carcinogenesis

    Directory of Open Access Journals (Sweden)

    Payne CM

    2011-05-01

    Full Text Available Claire M Payne, Cheray Crowley-Skillicorn, Carol Bernstein, Hana Holubec, Harris BernsteinDepartment of Cell Biology and Anatomy, College of Medicine, University of Arizona Tucson, AZ, USAAbstract: Chromosomal instability is a major pathway of sporadic colon carcinogenesis. Chromosome arm 1p appears to be one of the “hot spots” in the non-neoplastic mucosa that, when deleted, is associated with the initiation of carcinogenesis. Chromosome arm 1p contains genes associated with DNA repair, spindle checkpoint function, apoptosis, multiple microRNAs, the Wnt signaling pathway, tumor suppression, antioxidant activities, and defense against environmental toxins. Loss of 1p is dangerous since it would likely contribute to genomic instability leading to tumorigenesis. The 1p deletion-associated colon carcinogenesis pathways are reviewed at the molecular and cellular levels. Sporadic colon cancer is strongly linked to a high-fat/low-vegetable/low-micronutrient, Western-style diet. We also consider how selected dietary-related compounds (eg, excess hydrophobic bile acids, and low levels of folic acid, niacin, plant-derived antioxidants, and other modulatory compounds might affect processes leading to chromosomal deletions, and to the molecular and cellular pathways specifically altered by chromosome 1p loss.Keywords: chromosome 1p, colon carcinogenesis, molecular pathways, cellular pathways

  12. Thyroid carcinoma

    International Nuclear Information System (INIS)

    Friedman, M.; Skolnik, E.M.; Baim, H.M.; Becker, S.P.; Katz, A.H.; Mantravadi, R.V.

    1980-01-01

    Differentiated thyroid carcinoma was studied with regard to mode of presentation, initial findings, treatment and survival. The classic signs, symptoms, physical and scan findings were found to be present in approximately 70% of the patients. Prognosis was found to be dependent on age of presentation more than any other factor. Patients with prior exposure to radiation were found to have more extensive disease and require more extensive surgery but ultimately had the same prognosis for 15-year cure. Treatment for distant metastatic disease by surgery, radioactive iodine and external radiation all resulted in long-term survival in certain cases

  13. Carcinoma Basocelular

    OpenAIRE

    Inês Alencar de Castro; Lucio Bakos; Roberto Lopes Gervini

    2008-01-01

    Vemos na região frontal de um paciente masculino, fototipo II de Fitzpatrick, lesão ulcerada com bordas papulosas róseas e peroladas, correspondendo a Carcinoma Basocelular. É lesão maligna originária das células não- queratinizadas da camada basal da epiderme, sendo a forma mais comum de câncer em humanos. Estima-se em torno de 100.000 casos/ano no Brasil. Ocorre predominantemente em pele exposta de indivíduos com pouca capacidade de se bronzear. Pode se tornar invasivo, mas raramente metast...

  14. Clinical investigation of TROP-2 as an independent biomarker and potential therapeutic target in colon cancer.

    Science.gov (United States)

    Zhao, Peng; Yu, Hai-Zheng; Cai, Jian-Hui

    2015-09-01

    Colon cancer is associated with a severe demographic and economic burden worldwide. The pathogenesis of colon cancer is highly complex and involves sequential genetic and epigenetic mechanisms. Despite extensive investigation, the pathogenesis of colon cancer remains to be elucidated. As the third most common type of cancer worldwide, the treatment options for colon cancer are currently limited. Human trophoblast cell‑surface marker (TROP‑2), is a cell‑surface transmembrane glycoprotein overexpressed by several types of epithelial carcinoma. In addition, TROP‑2 has been demonstrated to be associated with tumorigenesis and invasiveness in solid types of tumor. The aim of the present study was to investigate the protein expression of TROP‑2 in colon cancer tissues, and further explore the association between the expression of TROP‑2 and clinicopathological features of patients with colon cancer. The expression and localization of the TROP‑2 protein was examined using western blot analysis and immunofluorescence staining. Finally, the expression of TROP‑2 expression was correlated to conventional clinicopathological features of colon cancer using a χ2 test. The results revealed that TROP‑2 protein was expressed at high levels in the colon cancer tissues, which was associated with the development and pathological process of colon cancer. Therefore, TROP‑2 may be used as a biomarker to determine the clinical prognosis, and as a potential therapeutic target in colon cancer.

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

    Science.gov (United States)

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

    2014-05-21

    Cytosolic nonspecific dipetidase (CN2) belongs to the family of M20 metallopeptidases. It was stated in previous articles that higher expression levels of CN2 were observed in renal cell carcinoma and breast cancer. Our study explored the correlation between CN2 and colon carcinogenesis. We analysed the relationship between 183 patients clinicopathological characteristics and its CN2 expression. To detect the levels of CN2 in colon cancer cell lines and colon cancer tissues by western blot. To verify cell proliferation in colon cancer cells with knockdown of CNDP2 and explore the causes of these phenomena. The expression levels of CN2 in clinical colon tumors and colon cancer cell lines were significantly higher than that in normal colon mucosa and colon cell lines. The difference in CN2 levels was associated with tumor location (right- and left-sided colon cancer), but there was no significant association with age, gender, tumor size, tumor grade, tumor stage or serum carcinoembryonic antigen (CEA). Knockdown of CNDP2 inhibited cell proliferation, blocked cell cycle progression and retarded carcinogenesis in an animal model. The signaling pathway through which knockdown of CNDP2 inhibited cell proliferation and tumorigenesis involved in EGFR, cyclin B1 and cyclin E. Knockdown of CNDP2 can inhibit the proliferation of colon cancer in vitro and retarded carcinogenesis in vivo.

  16. Predictors of Preoperative Tinnitus in Unilateral Sporadic Vestibular Schwannoma

    Directory of Open Access Journals (Sweden)

    Georgios Naros

    2017-08-01

    Full Text Available ObjectiveNearly two-thirds of patients with vestibular schwannoma (VS are reporting a significantly impaired quality of life due to tinnitus. VS-associated tinnitus is attributed to an anatomical and physiological damage of the hearing nerve by displacing growth of the tumor. In contrast, the current pathophysiological concept of non-VS tinnitus hypothesizes a maladaptive neuroplasticity of the central nervous system to a (hidden hearing impairment resulting in a subjective misperception. However, it is unclear whether this concept fits to VS-associated tinnitus. This study aims to determine the clinical predictors of VS-associated tinnitus to ascertain the compatibility of both pathophysiological concepts.MethodsThis retrospective study includes a group of 478 neurosurgical patients with unilateral sporadic VS evaluated preoperatively regarding the occurrence of ipsilateral tinnitus depending on different clinical factors, i.e., age, gender, tumor side, tumor size (T1–T4 according to the Hannover classification, and hearing impairment (Gardner–Robertson classification, GR1–5, using a binary logistic regression.Results61.8% of patients complain about a preoperative tinnitus. The binary logistic regression analysis identified male gender [OR 1.90 (1.25–2.75; p = 0.002] and hearing impairment GR3 [OR 1.90 (1.08–3.35; p = 0.026] and GR4 [OR 8.21 (2.29–29.50; p = 0.001] as positive predictors. In contrast, patients with large T4 tumors [OR 0.33 (0.13–0.86; p = 0.024] and complete hearing loss GR5 [OR 0.36 (0.15–0.84; p = 0.017] were less likely to develop a tinnitus. Yet, 60% of the patients with good clinical hearing (GR1 and 25% of patients with complete hearing loss (GR5 suffered from tinnitus.ConclusionThese data are good accordance with literature about non-VS tinnitus indicating hearing impairment as main risk factor. In contrast, complete hearing loss appears a negative predictor for tinnitus. For the first

  17. SDHAF2 mutations in familial and sporadic paraganglioma and phaeochromocytoma.

    Science.gov (United States)

    Bayley, Jean-Pierre; Kunst, Henricus P M; Cascon, Alberto; Sampietro, Maria Lourdes; Gaal, José; Korpershoek, Esther; Hinojar-Gutierrez, Adolfo; Timmers, Henri J L M; Hoefsloot, Lies H; Hermsen, Mario A; Suárez, Carlos; Hussain, A Karim; Vriends, Annette H J T; Hes, Frederik J; Jansen, Jeroen C; Tops, Carli M; Corssmit, Eleonora P; de Knijff, Peter; Lenders, Jacques W M; Cremers, Cor W R J; Devilee, Peter; Dinjens, Winand N M; de Krijger, Ronald R; Robledo, Mercedes

    2010-04-01

    Paragangliomas and phaeochromocytomas are neuroendocrine tumours associated frequently with germline mutations of SDHD, SDHC, and SDHB. Previous studies have shown the imprinted SDHAF2 gene to be mutated in a large Dutch kindred with paragangliomas. We aimed to identify SDHAF2 mutation carriers, assess the clinical genetic significance of SDHAF2, and describe the associated clinical phenotype. We undertook a multicentre study in Spain and The Netherlands in 443 apparently sporadic patients with paragangliomas and phaeochromocytomas who did not have mutations in SDHD, SDHC, or SDHB. We analysed DNA of 315 patients for germline mutations of SDHAF2; a subset (n=200) was investigated for gross gene deletions. DNA from a group of 128 tumours was studied for somatic mutations. We also examined a Spanish family with head and neck paragangliomas with a young age of onset for the presence of SDHAF2 mutations, undertook haplotype analysis in this kindred, and assessed their clinical phenotype. We did not identify any germline or somatic mutations of SDHAF2, and no gross gene deletions were noted in the subset of apparently sporadic patients analysed. Investigation of the Spanish family identified a pathogenic germline DNA mutation of SDHAF2, 232G-->A (Gly78Arg), identical to the Dutch kindred. SDHAF2 mutations do not have an important role in phaeochromocytoma and are rare in head and neck paraganglioma. Identification of a second family with the Gly78Arg mutation suggests that this is a crucial residue for the function of SDHAF2. We conclude that SDHAF2 mutation analysis is justified in very young patients with isolated head and neck paraganglioma without mutations in SDHD, SDHC, or SDHB, and in individuals with familial antecedents who are negative for mutations in all other risk genes. Dutch Cancer Society, European Union 6th Framework Program, Fondo Investigaciones Sanitarias, Fundación Mutua Madrileña, and Red Temática de Investigación Cooperativa en Cáncer. 2010

  18. Sporadic cases of adult measles: a research article.

    Science.gov (United States)

    Premaratna, Ranjan; Luke, Nathasha; Perera, Harsha; Gunathilake, Mahesh; Amarasena, Pubudu; Chandrasena, T G A Nilmini

    2017-01-10

    Measles caused by a paramyxovirus, characterized by fever, malaise, cough, coryza conjunctivitis, a maculopapular rash is known to result in pneumonia, encephalitis and death. Fatal cases of measles in Sri Lanka are rare after implementation of the National Immunization Programme in 1984. Thereafter 0.1% case fatality rate was observed during October 1999-June 2000 which is a very low figure compared to other regional countries. Immunization guidelines were further revised in 2001, 2011 and in 2012 when additional immunization was recommended to age group 4-21 years; who are likely to have inadequate immunization, in order to achieve elimination of Measles by 2020. However, in 2013-2014, 4690 cases were reported and the majority were children less than 1 year of age. The occurrence in adults is hard to retrieve in published epidemiological reports, however had been 38% (out of 1008 patients) in the 3rd quarter of 2013. During this outbreak 73/101 (72%) reported from the North Central Province of Sri Lanka had been more than 12 years of age with 50% being more than 29 years. 14 Sri lankan adult patients [median age 32 years (range 25-48)] who presented sporadically from June 2014 to March 2016, with confirmed measles infection were enrolled retrospectively after informed consent. Details with regards to their clinical presentation, immunization and other relevant areas were collected using an interviewer administered questionnaire or using patient management records. The patients presented with high fever, headache, severe body aches, sore throat, dry cough, intense tearing, red eyes and posterior cervical lymphadenopathy over 3-5 days duration. Later they developed discrete maculopapular rash helping the diagnosis. They had a variable degree of leucopenia, lymphocytosis, thrombocytopenia and derangements in the liver functions mimicking any other acute febrile illnesses such as dengue, chikungunya, leptospirosis or Zika virus infection. At least a 3-5

  19. Periampullary carcinomas.

    Science.gov (United States)

    Filiz, Gulaydan; Yerci, Omer; Adim, Saduman Balaban; Gurel, Selim; Dolar, Enver; Memik, Faruk

    2007-06-01

    The purpose of this study was to determine predictors of survival after resection for periampullary neoplasms. In this study, we reevaluated our 17 cases of this type tumor which we had reported as periampullar site tumors, in advanced stages with undetermined localization, in our pathology department of the Uludag University faculty of medicine. Six of our cases were female, and 11 were male with a mean age of 60.6 years (range 31-77). Their main complaints were loss of weight, anorexia, jaundice and fatigue. Physical and endoscopic examination of these patients revealed periampullary mass and Whipple operations were performed on all of them. Histopathologic examinations of these tumors revealed adenocarcinoma in 15, small cell (neuroendocrin) carcinoma in two. All were in the advanced stages. Eight of them were alive and free of disease after 1.5- to 20-month follow-ups, while ten died because of disease. Periampullary carcinoma is a problem with increasing clinical significance. Tumor size, tumor type and differentiation, lymph node status appears to be prognostic markers.

  20. P62/Ubiquitin IHC expression in gastrointestinal carcinomas

    Directory of Open Access Journals (Sweden)

    Amr eMohamed

    2015-03-01

    Full Text Available P62 and ubiquitin are small regulatory proteins demonstrated to have implications in the prognosis and survival of various malignancies including: hepatocellular, breast, ovarian, and some gastrointestinal carcinomas. Several trials studied the link of their activity to the extrinsic apoptosis pathway and showed that their autophagy modification has a critical stand point in tumorigenesis. These findings explain their vital role in controlling the process of cell death and survival. It has been shown recently that p62 and ubiquitin overexpression in different types of cancers, such as triple negative breast and ovarian cancers, have directly correlated with incidence of distant metastases. We aim to evaluate p62/ubiquitin expression in gastrointestinal carcinomas of gastric, colonic and pancreatic origin. In gastric carcinoma (45, positive p62 nuclear expression was noted in 53% and cytoplasmic in 57%, while positive ubiquitin was nuclear expressed in 80%, and cytoplasmic in 24%. In colon carcinoma (70, positive p62 nuclear expression was noted in 41% and cytoplasmic in 68.5%, while positive ubiquitin was nuclear in 57% and cytoplasmic in 42%. In pancreatic cancer, positive p62 nuclear expression was noted in 86% and cytoplasmic in 60%, while positive ubiquitin was nuclear in 100% and cytoplasmic in 80%. Normal gastric (6, colon (4 and pancreatic (4 tissues were negative for both P62 and ubiquitin (nuclear and cytoplasmic staining <20%. The results suggest that p62 and ubiquitin are highly expressed in nuclei and cytoplasm of gastric, colonic and pancreatic carcinomas. More studies are needed to correlate IHC expression of p62/ubiquitin with clinicopathologic parameters and overall survival in GI carcinomas.

  1. EZH2 depletion blocks the proliferation of colon cancer cells.

    Directory of Open Access Journals (Sweden)

    Bettina Fussbroich

    Full Text Available The Enhancer of Zeste 2 (EZH2 protein has been reported to stimulate cell growth in some cancers and is therefore considered to represent an interesting new target for therapeutic intervention. Here, we investigated a possible role of EZH2 for the growth control of colon cancer cells. RNA interference (RNAi-mediated intracellular EZH2 depletion led to cell cycle arrest of colon carcinoma cells at the G1/S transition. This was associated with a reduction of cell numbers upon transient transfection of synthetic EZH2-targeting siRNAs and with inhibition of their colony formation capacity upon stable expression of vector-borne siRNAs. We furthermore tested whether EZH2 may repress the growth-inhibitory p27 gene, as reported for pancreatic cancer. However, expression analyses of colon cancer cell lines and colon cancer biopsies did not reveal a consistent correlation between EZH2 and p27 levels. Moreover, EZH2 depletion did not re-induce p27 expression in colon cancer cells, indicating that p27 repression by EZH2 may be cell- or tissue-specific. Whole genome transcriptome analyses identified cellular genes affected by EZH2 depletion in colon cancer cell lines. They included several cancer-associated genes linked to cellular proliferation or invasion, such as Dag1, MageD1, SDC1, Timp2, and Tob1. In conclusion, our results demonstrate that EZH2 depletion blocks the growth of colon cancer cells. These findings might provide benefits for the treatment of colon cancer.

  2. Sodium butyrate increases expression of the coxsackie and adenovirus receptor in colon cancer cells.

    Science.gov (United States)

    Küster, Katrin; Grötzinger, Carsten; Koschel, Annika; Fischer, Andreas; Wiedenmann, Bertram; Anders, Mario

    2010-03-01

    Histone deacetylase inhibitors (HDACI), e.g., sodium butyrate (NaB), have been suggested to upregulate the coxsackie and adenovirus receptor (CAR). Its impact on CAR in colon carcinomas, however, is poorly understood. NaB treatment of colon cancer cells increased CAR expression preferentially in cell lines with low basic CAR levels. These findings suggest that downregulation of CAR gene expression is mediated by transcriptional regulation and that activation of the CAR gene promoter is modulated by histone acetylation. The employment of HDACI may, therefore, represent a promising approach for improving adenovirus-based therapies of colon cancers with low CAR expression levels.

  3. Recent trend of colonic diverticulosis

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Yae Soon; Lee, Sung Woo; Han, Chang Yul; Lee, Kwan Seh [Inje Medical College, Seoul (Korea, Republic of)

    1988-08-15

    Colonic Diverticulosis is once thought to be a rare disease in Korea compared with western countries, but the incidence has been increasing with passage of time. Authors reviewed 151 cases of colon study with new double contrast method performed from November, 1986 to March, 1987 at Paik Hospital Inje college. The results were as follow: 1. The colonic diverticulosis was found in 39 cases out of 151 colon study (25.8%). 2. Colonic Diverticulosis were located at right and transvercolon in 54% and left and sigmoid colon in 18%. 3. Increasing occurrence in younger age group predilection; 4th decade was observed.

  4. Recent trend of colonic diverticulosis

    International Nuclear Information System (INIS)

    Chung, Yae Soon; Lee, Sung Woo; Han, Chang Yul; Lee, Kwan Seh

    1988-01-01

    Colonic Diverticulosis is once thought to be a rare disease in Korea compared with western countries, but the incidence has been increasing with passage of time. Authors reviewed 151 cases of colon study with new double contrast method performed from November, 1986 to March, 1987 at Paik Hospital Inje college. The results were as follow: 1. The colonic diverticulosis was found in 39 cases out of 151 colon study (25.8%). 2. Colonic Diverticulosis were located at right and transvercolon in 54% and left and sigmoid colon in 18%. 3. Increasing occurrence in younger age group predilection; 4th decade was observed.

  5. CT findings of colonic diverticulitis

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, Shigeru; Ohba, Satoru [Nagoya City Univ. (Japan). Medical School; Mizutani, Masaru [and others

    1998-11-01

    Although colonic diverticulitis has no indication for operation, but in some mistaken cases were operated with a diagnosis of acute appendicitis. We evaluated the CT findings of colonic diverticulitis about 19 cases and of asymptomatic colonic diverticula about 15 cases retrospectively. Diagnosis was confirmed of barium enema and operation. CT are complementary methods of examination that can delineated the range of thickening of the colon and the extension of inflammatory changes around the colon. We also believe that CT findings of colonic diverticulitis are useful for differentiating from a diagnosis of appendicitis. (author)

  6. CT findings of colonic diverticulitis

    International Nuclear Information System (INIS)

    Sasaki, Shigeru; Ohba, Satoru; Mizutani, Masaru

    1998-01-01

    Although colonic diverticulitis has no indication for operation, but in some mistaken cases were operated with a diagnosis of acute appendicitis. We evaluated the CT findings of colonic diverticulitis about 19 cases and of asymptomatic colonic diverticula about 15 cases retrospectively. Diagnosis was confirmed of barium enema and operation. CT are complementary methods of examination that can delineated the range of thickening of the colon and the extension of inflammatory changes around the colon. We also believe that CT findings of colonic diverticulitis are useful for differentiating from a diagnosis of appendicitis. (author)

  7. Hereditary colon Cancer: Recommendations for prevention

    International Nuclear Information System (INIS)

    Sarroca, C.

    2004-01-01

    Prevention in individuals with hereditary risk of colon cancer, is subject to clinical and molecular facts because their behavior differs to sporadic cancer. Hereditary cancer diseases affecting the colon in particular linked to other locations or that are associated with pre-cancer (polyps, osteoma s, lentigines) phenotypic markers represent a dissimilar to those who present directly in colorectal cancer status or associated conditions. In the first, the presence of previous injury (phenotypes) allows us to identify, while the latter is essential to have other diagnostic pathway (genotypes) .The location of genomic alterations manages to delve into the problem and identify those who will develop disease. The perspective will be different in the general population and those who do not carry mutations in terms suggestions for prevention, both primary and secondary. Not always the mutation is detected and in these high-risk situations, the clinic is sovereign and agrees to keep all members of these events surveillance strict about not being able to characterize those who are carriers of alterations and our condition is different in the proposition of preventive attitudes: set from when control about which organs and often starts, suffer because of accelerated carcinogenesis. The presentation is focused on populations at increased risk of cancer colorectal, regarding the management of the suggestions for primary prevention, secondary prevention while analyzing the early diagnosis of the disease and the suggestion of treatment, compared to the general population management. Primary prevention, including chemo prevention are described. While in secondary prevention is emphasized to management time tracking, optimization diagnostics according to the pathology suspected, the most common therapeutic approaches and findings relating prophylactic surgery

  8. CAMS newly detected meteor showers and the sporadic background

    Science.gov (United States)

    Jenniskens, P.; Nénon, Q.; Gural, P. S.; Albers, J.; Haberman, B.; Johnson, B.; Morales, R.; Grigsby, B. J.; Samuels, D.; Johannink, C.

    2016-03-01

    The Cameras for Allsky Meteor Surveillance (CAMS) video-based meteoroid orbit survey adds 60 newly identified showers to the IAU Working List of Meteor Showers (numbers 427, 445-446, 506-507, and part of 643-750). 28 of these are also detected in the independent SonotaCo survey. In total, 230 meteor showers and shower components are identified in CAMS data, 177 of which are detected in at least two independent surveys. From the power-law size frequency distribution of detected showers, we extrapolate that 36% of all CAMS-observed meteors originated from ∼700 showers above the N = 1 per 110,000 shower limit. 71% of mass falling to Earth from streams arrives on Jupiter-family type orbits. The transient Geminids account for another 15%. All meteoroids not assigned to streams form a sporadic background with highest detected numbers from the apex source, but with 98% of mass falling in from the antihelion source. Even at large ∼7-mm sizes, a Poynting-Robertson drag evolved population is detected, which implies that the Grün et al. collisional lifetimes at these sizes are underestimated by about a factor of 10. While these large grains survive collisions, many fade on a 104-y timescale, possibly because they disintegrate into smaller particles by processes other than collisions, leaving a more resilient population to evolve.

  9. Radiosurgical treatment of sporadic vestibular schwannomas: A prospective cohort study

    International Nuclear Information System (INIS)

    Martel V, Freddy; Iniguez S, Rodrigo; Venencia M, Daniel; Tagle M, Patricio; Besa D, Pelayo; Lorenzoni S, Jose

    2008-01-01

    Objective: To analyze the preliminary experience of radiosurgery for Vestibular Schwannomas at the Pontificia Universidad Catolica de Chile. Material and methods: The first 17 patients with sporadic Vestibular Schwannomas treated by radiosurgery at our institution are reported. The marginal dose used was 12 to 12.5 Gy. prescribed at the 70 or 80 isodose fine. Patients were controlled at 6, 12 and 24 months with magnetic resonance, audiometric study and clinical examination. Results: In all of the 17 patients treated a decrease tumor enhancement on MR was demonstrated. In 16 patients (94%) a pattern of central tumor necrosis was observed during the firs year Actuarial useful hearing was maintained in 62.5% at 2 year after treatment. Facial nerve function was maintained in all of the 15 patients with normal function at treatment (100%). Trigeminal function was maintained in ah of the 14 patients (100%) with previous normal trigeminal function. The mean time to return to work or normal activities was 11.5 days after treatment. Conclusions: These preliminary results are comparable with results published in the literature and reinforce the demonstrate role of radiosurgery in the management of vestibular schwannomas

  10. A review of drug therapy for sporadic fatal insomnia.

    Science.gov (United States)

    Tabaee Damavandi, Pardis; Dove, Martin T; Pickersgill, Richard W

    2017-09-03

    Sporadic fatal insomnia (sFI) is a rapid progressive neurodegenerative disease characterised by gradual to perpetual insomnia, followed by dysautonomia, coma and death. 1 The cause of sFI was recently mapped to a mutation in a protein, the prion, found in the human brain. It is the unfolding of the prion that leads to the generation of toxic oligomers that destroy brain tissue and function. Recent studies have confirmed that a methionine mutation at codon 129 of the human Prion is characteristic of sFI. Current treatment slows down the progression of the disease, but no cure has been found, yet. We used Molecular Docking and Molecular Dynamics simulation methods, to study the toxic Fatal-Insomnia-prion conformations at local unfolding. The idea was to determine these sites and to stabilise these regions against unfolding and miss-folding, using a small ligand, based on a phenothiazine "moiety". As a result we here discuss current fatal insomnia therapy and present seven novel possible compounds for in vitro and in vivo screening.

  11. Facing and managing natural disasters in the Sporades islands, Greece

    Science.gov (United States)

    Karanikola, P.; Panagopoulos, T.; Tampakis, S.; Karantoni, M. I.; Tsantopoulos, G.

    2014-04-01

    The region of the Sporades islands located in central Greece is at the mercy of many natural phenomena, such as earthquakes due to the marine volcano Psathoura and the rift of Anatolia, forest fires, floods, landslides, storms, hail, snowfall and frost. The present work aims at studying the perceptions and attitudes of the residents regarding how they face and manage natural disasters. A positive public response during a hazard crisis depends not only upon the availability and good management of a civil defense plan but also on the knowledge and perception of the possible hazards by the local population. It is important for the stakeholders to know what the citizens expect so that the necessary structures can be developed in the phase of preparation and organization. The residents were asked their opinion about what they think should be done by the stakeholders after a catastrophic natural disaster, particularly about the immediate response of stakeholders and their involvement and responsibilities at different, subsequent intervals of time following the disaster. The residents were also asked about the most common disasters that happen in their region and about the preparation activities of the stakeholders.

  12. [Lung transplantation in sporadic lymphangioleiomyomatosis: study of 7 cases].

    Science.gov (United States)

    Ansótegui Barrera, Emilio; Mancheño Franch, Nuria; Peñalver Cuesta, Juan Carlos; Vera-Sempere, Francisco; Padilla Alarcón, José

    2013-10-19

    Sporadic lymphangioleiomyomatosis (S-LAM) is a rare disease that affects only women. It is characterized by an abnormal proliferation of immature smooth muscle cells (LAM cells) that grow in an aberrant manner in the airway, parenchymal lung lymph and blood vessels, determining the onset of pulmonary cystic lesions. The disease has no treatment, progressing to respiratory failure, and lung transplantation (LT) may be a treatment option at this stage. Our goal was to study 7 patients undergoing LT for S-LAM. We studied a series of clinical and demographic characteristics, diagnostic modality and post-transplant outcomes. We performed a descriptive analysis of the series. The Kaplan-Meier method was used to estimate survival. The mean age of onset of symptoms was 35 years, the diagnosis of 37 years and that of LT 38 years. The most common symptom was dyspnea. Four patients had a history of pneumothorax and pleural effusion. The mean forced expiratory volume in one second was 32.7% and the diffusing capacity for carbon monoxide was 29%. All patients were subjected to LT and survival was 100, 85.7 and 57.1% at one, 3 and 5 years, respectively. Three died of bronchiolitis obliterans and 2 necropsies did not show evidence of disease recurrence. LT is a therapeutic option in patients with S-LAM with an advanced respiratory functional impairment. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  13. Thyroid Sporadic Goiter with Adult Heterotopic Bone Formation

    Directory of Open Access Journals (Sweden)

    Adriana Handra-Luca

    2015-01-01

    Full Text Available Thyroid heterotopic bone formation (HBF in goiter is a rare finding. Five thyroid resection specimens were analyzed for HBF. The results were correlated with clinicomorphological features. All patients were women (33–82 years. The preoperative diagnosis was thyroid goiter or nodule. Treatment consisted in thyroidectomy and lobectomy (3 and 2, resp.. Microscopy showed sporadic nodular goiter. Malformative blood vessels and vascular calcifications were seen in intra- and extrathyroid location (5 and 3, resp.. The number and size of HBFs (total: 28 ranged between 1 and 23/thyroid gland (one bilateral and 1 and 10 mm, respectively. Twelve HBFs were in contact with the thyroid capsule. Most were extranodular (21, versus 6 intranodular. The medical history was positive for dyslipidemia, hyperglycemia, renal dysfunction, and hyperuricemia (2, 3, and 3 cases and 1 case, resp. without any parathyroid abnormality. In conclusion, thyroid HBF may be characterized by subcapsular or extranodular location, various size (usually ≥2 mm, and vascular calcifications and malformations. Features of metabolic syndrome and renal dysfunction may be present, but their exact role in the pathogenesis of HBFs remains to be elucidated.

  14. Vulvar carcinoma

    International Nuclear Information System (INIS)

    Anderson, John M.; Cassady, J. Robert; Shimm, David S.; Stea, Baldassarre

    1995-01-01

    Purpose: Controversies exist regarding the use of radiation therapy in the treatment of vulvar carcinoma. A retrospective review was performed to evaluate our institution's experience with surgery and radiation for this disease. Methods and Materials: The medical records of 47 patients treated for squamous cell carcinoma of the vulva at our institution (1974-1992) were reviewed for TNM stage (AJCC criteria), treatment modality, and associated 5-year local control and survival based on Kaplan-Meier analysis. Results: Twenty-eight patients (60%) presented with Stage I and II disease and their 5-year survival was 69%. Stage III patients accounted for 12 (25%) of the patients and their 5-year survival was 73%. Seven patients presented with Stage IV disease and five died within 13 months of diagnosis after predominantly palliative therapy. The 40 patients with Stages I, II, and III disease were treated aggressively and were further evaluated for treatment-modality-associated survival and local control. Radiation therapy was used as primary treatment in nine patients, of whom seven were treated with radiation alone and two were treated postoperatively after wide excision. Surgery alone was performed in 31 patients consisting of either radical vulvectomy (20 patients) or wide excision (11 patients). When comparing outcomes of radical vulvectomy vs. radiation therapy, we noted that the 5-year actuarial survivals were comparable (74% for either modality), despite the presence of more favorable prognostic factors in the group treated with radical vulvectomy. Patients treated with wide excision alone had a trend for a poorer 5-year actuarial survival (51%) and local control (50%). Conclusions: Radical vulvectomy offers good locoregional control and survival. This retrospective review further supports the use of radiation therapy with conservative surgery as an alternative treatment option for patients with vulvar carcinoma treated with curative intent. In contrast, the use of

  15. Tubulin glycylases are required for primary cilia, control of cell proliferation and tumor development in colon

    Science.gov (United States)

    Rocha, Cecilia; Papon, Laura; Cacheux, Wulfran; Marques Sousa, Patricia; Lascano, Valeria; Tort, Olivia; Giordano, Tiziana; Vacher, Sophie; Lemmers, Benedicte; Mariani, Pascale; Meseure, Didier; Medema, Jan Paul; Bièche, Ivan; Hahne, Michael; Janke, Carsten

    2014-01-01

    TTLL3 and TTLL8 are tubulin glycine ligases catalyzing posttranslational glycylation of microtubules. We show here for the first time that these enzymes are required for robust formation of primary cilia. We further discover the existence of primary cilia in colon and demonstrate that TTLL3 is the only glycylase in this organ. As a consequence, colon epithelium shows a reduced number of primary cilia accompanied by an increased rate of cell division in TTLL3-knockout mice. Strikingly, higher proliferation is compensated by faster tissue turnover in normal colon. In a mouse model for tumorigenesis, lack of TTLL3 strongly promotes tumor development. We further demonstrate that decreased levels of TTLL3 expression are linked to the development of human colorectal carcinomas. Thus, we have uncovered a novel role for tubulin glycylation in primary cilia maintenance, which controls cell proliferation of colon epithelial cells and plays an essential role in colon cancer development. PMID:25180231

  16. Gut-associated Lymphoid Tissue (GALT) Carcinoma in Ulcerative Colitis.

    Science.gov (United States)

    Rubio, Carlos A; DE Petris, Giovanni; Puppa, Giacomo

    2018-02-01

    In ulcerative colitis (UC), the majority of colorectal carcinomas (CRC) arise in the vast colorectal mucosal domain built with mucus-producing goblet cells and columnar cells. Conversely, CRC in UC rarely evolve in the tiny, spotty gut-associated lymphoid tissue (GALT) mucosal domain. Here we review the four reported cases of colonic carcinoma developing in GALT mucosa in UC, searching for possible precursor lesions connected with the evolution of these tumours. The clinical history, age, gender, endoscopic descriptions, and the pathology (localization, gross and histological descriptions of the luminal surface) of the four UC-GALT carcinomas reported in the literature were reviewed. The luminal surface in three out of the four carcinomas revealed conventional (tubular/villous) adenomas or high-grade dysplasia. All four UC-GALT-carcinomas were detected at an early stage (T1N0). GALT carcinomas do occur, albeit infrequently, in patients with UC. The finding that three out of the four GALT carcinomas on record were covered by conventional adenomas or by high-grade dysplasia strongly suggests that non-invasive conventional neoplasias might often precede GALT carcinomas in UC. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  17. Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma.

    Science.gov (United States)

    Linehan, W Marston; Spellman, Paul T; Ricketts, Christopher J; Creighton, Chad J; Fei, Suzanne S; Davis, Caleb; Wheeler, David A; Murray, Bradley A; Schmidt, Laura; Vocke, Cathy D; Peto, Myron; Al Mamun, Abu Amar M; Shinbrot, Eve; Sethi, Anurag; Brooks, Samira; Rathmell, W Kimryn; Brooks, Angela N; Hoadley, Katherine A; Robertson, A Gordon; Brooks, Denise; Bowlby, Reanne; Sadeghi, Sara; Shen, Hui; Weisenberger, Daniel J; Bootwalla, Moiz; Baylin, Stephen B; Laird, Peter W; Cherniack, Andrew D; Saksena, Gordon; Haake, Scott; Li, Jun; Liang, Han; Lu, Yiling; Mills, Gordon B; Akbani, Rehan; Leiserson, Mark D M; Raphael, Benjamin J; Anur, Pavana; Bottaro, Donald; Albiges, Laurence; Barnabas, Nandita; Choueiri, Toni K; Czerniak, Bogdan; Godwin, Andrew K; Hakimi, A Ari; Ho, Thai H; Hsieh, James; Ittmann, Michael; Kim, William Y; Krishnan, Bhavani; Merino, Maria J; Mills Shaw, Kenna R; Reuter, Victor E; Reznik, Ed; Shelley, Carl S; Shuch, Brian; Signoretti, Sabina; Srinivasan, Ramaprasad; Tamboli, Pheroze; Thomas, George; Tickoo, Satish; Burnett, Kenneth; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph D; Penny, Robert J; Shelton, Candace; Shelton, W Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Avedon, Melissa T; Bowen, Jay; Gastier-Foster, Julie M; Gerken, Mark; Leraas, Kristen M; Lichtenberg, Tara M; Ramirez, Nilsa C; Santos, Tracie; Wise, Lisa; Zmuda, Erik; Demchok, John A; Felau, Ina; Hutter, Carolyn M; Sheth, Margi; Sofia, Heidi J; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C; Zhang, Jiashan; Ayala, Brenda; Baboud, Julien; Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Ally, Adrian; Balasundaram, Miruna; Balu, Saianand; Beroukhim, Rameen; Bodenheimer, Tom; Buhay, Christian; Butterfield, Yaron S N; Carlsen, Rebecca; Carter, Scott L; Chao, Hsu; Chuah, Eric; Clarke, Amanda; Covington, Kyle R; Dahdouli, Mahmoud; Dewal, Ninad; Dhalla, Noreen; Doddapaneni, Harsha V; Drummond, Jennifer A; Gabriel, Stacey B; Gibbs, Richard A; Guin, Ranabir; Hale, Walker; Hawes, Alicia; Hayes, D Neil; Holt, Robert A; Hoyle, Alan P; Jefferys, Stuart R; Jones, Steven J M; Jones, Corbin D; Kalra, Divya; Kovar, Christie; Lewis, Lora; Li, Jie; Ma, Yussanne; Marra, Marco A; Mayo, Michael; Meng, Shaowu; Meyerson, Matthew; Mieczkowski, Piotr A; Moore, Richard A; Morton, Donna; Mose, Lisle E; Mungall, Andrew J; Muzny, Donna; Parker, Joel S; Perou, Charles M; Roach, Jeffrey; Schein, Jacqueline E; Schumacher, Steven E; Shi, Yan; Simons, Janae V; Sipahimalani, Payal; Skelly, Tara; Soloway, Matthew G; Sougnez, Carrie; Tam, Angela; Tan, Donghui; Thiessen, Nina; Veluvolu, Umadevi; Wang, Min; Wilkerson, Matthew D; Wong, Tina; Wu, Junyuan; Xi, Liu; Zhou, Jane; Bedford, Jason; Chen, Fengju; Fu, Yao; Gerstein, Mark; Haussler, David; Kasaian, Katayoon; Lai, Phillip; Ling, Shiyun; Radenbaugh, Amie; Van Den Berg, David; Weinstein, John N; Zhu, Jingchun; Albert, Monique; Alexopoulou, Iakovina; Andersen, Jeremiah J; Auman, J Todd; Bartlett, John; Bastacky, Sheldon; Bergsten, Julie; Blute, Michael L; Boice, Lori; Bollag, Roni J; Boyd, Jeff; Castle, Erik; Chen, Ying-Bei; Cheville, John C; Curley, Erin; Davies, Benjamin; DeVolk, April; Dhir, Rajiv; Dike, Laura; Eckman, John; Engel, Jay; Harr, Jodi; Hrebinko, Ronald; Huang, Mei; Huelsenbeck-Dill, Lori; Iacocca, Mary; Jacobs, Bruce; Lobis, Michael; Maranchie, Jodi K; McMeekin, Scott; Myers, Jerome; Nelson, Joel; Parfitt, Jeremy; Parwani, Anil; Petrelli, Nicholas; Rabeno, Brenda; Roy, Somak; Salner, Andrew L; Slaton, Joel; Stanton, Melissa; Thompson, R Houston; Thorne, Leigh; Tucker, Kelinda; Weinberger, Paul M; Winemiller, Cynthia; Zach, Leigh Anne; Zuna, Rosemary

    2016-01-14

    Papillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal-cell carcinoma, and no effective forms of therapy for advanced disease exist. We performed comprehensive molecular characterization of 161 primary papillary renal-cell carcinomas, using whole-exome sequencing, copy-number analysis, messenger RNA and microRNA sequencing, DNA-methylation analysis, and proteomic analysis. Type 1 and type 2 papillary renal-cell carcinomas were shown to be different types of renal cancer characterized by specific genetic alterations, with type 2 further classified into three individual subgroups on the basis of molecular differences associated with patient survival. Type 1 tumors were associated with MET alterations, whereas type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-antioxidant response element (ARE) pathway. A CpG island methylator phenotype (CIMP) was observed in a distinct subgroup of type 2 papillary renal-cell carcinomas that was characterized by poor survival and mutation of the gene encoding fumarate hydratase (FH). Type 1 and type 2 papillary renal-cell carcinomas were shown to be clinically and biologically distinct. Alterations in the MET pathway were associated with type 1, and activation of the NRF2-ARE pathway was associated with type 2; CDKN2A loss and CIMP in type 2 conveyed a poor prognosis. Furthermore, type 2 papillary renal-cell carcinoma consisted of at least three subtypes based on molecular and phenotypic features. (Funded by the National Institutes of Health.).

  18. Comprehensive Molecular Characterization of Papillary Renal Cell Carcinoma

    Science.gov (United States)

    Linehan, W. Marston; Spellman, Paul T.; Ricketts, Christopher J.; Creighton, Chad J.; Fei, Suzanne S.; Davis, Caleb; Wheeler, David A.; Murray, Bradley A.; Schmidt, Laura; Vocke, Cathy D.; Peto, Myron; Al Mamun, Abu Amar M.; Shinbrot, Eve; Sethi, Anurag; Brooks, Samira; Rathmell, W. Kimryn; Brooks, Angela N.; Hoadley, Katherine A.; Robertson, A. Gordon; Brooks, Denise; Bowlby, Reanne; Sadeghi, Sara; Shen, Hui; Weisenberger, Daniel J.; Bootwalla, Moiz; Baylin, Stephen B.; Laird, Peter W.; Cherniack, Andrew D.; Saksena, Gordon; Haake, Scott; Li, Jun; Liang, Han; Lu, Yiling; Mills, Gordon B.; Akbani, Rehan; Leiserson, Mark D.M.; Raphael, Benjamin J.; Anur, Pavana; Bottaro, Donald; Albiges, Laurence; Barnabas, Nandita; Choueiri, Toni K.; Czerniak, Bogdan; Godwin, Andrew K.; Hakimi, A. Ari; Ho, Thai; Hsieh, James; Ittmann, Michael; Kim, William Y.; Krishnan, Bhavani; Merino, Maria J.; Mills Shaw, Kenna R.; Reuter, Victor E.; Reznik, Ed; Shelley, Carl Simon; Shuch, Brian; Signoretti, Sabina; Srinivasan, Ramaprasad; Tamboli, Pheroze; Thomas, George; Tickoo, Satish; Burnett, Kenneth; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph D.; Penny, Robert J.; Shelton, Candace; Shelton, W. Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Avedon, Melissa T.; Bowen, Jay; Gastier-Foster, Julie M.; Gerken, Mark; Leraas, Kristen M.; Lichtenberg, Tara M.; Ramirez, Nilsa C.; Santos, Tracie; Wise, Lisa; Zmuda, Erik; Demchok, John A.; Felau, Ina; Hutter, Carolyn M.; Sheth, Margi; Sofia, Heidi J.; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C.; Zhang, Jiashan (Julia); Ayala, Brenda; Baboud, Julien; Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Ally, Adrian; Balasundaram, Miruna; Balu, Saianand; Beroukhim, Rameen; Bodenheimer, Tom; Buhay, Christian; Butterfield, Yaron S.N.; Carlsen, Rebecca; Carter, Scott L.; Chao, Hsu; Chuah, Eric; Clarke, Amanda; Covington, Kyle R.; Dahdouli, Mahmoud; Dewal, Ninad; Dhalla, Noreen; Doddapaneni, HarshaVardhan; Drummond, Jennifer; Gabriel, Stacey B.; Gibbs, Richard A.; Guin, Ranabir; Hale, Walker; Hawes, Alicia; Hayes, D. Neil; Holt, Robert A.; Hoyle, Alan P.; Jefferys, Stuart R.; Jones, Steven J.M.; Jones, Corbin D.; Kalra, Divya; Kovar, Christie; Lewis, Lora; Li, Jie; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Meng, Shaowu; Meyerson, Matthew; Mieczkowski, Piotr A.; Moore, Richard A.; Morton, Donna; Mose, Lisle E.; Mungall, Andrew J.; Muzny, Donna; Parker, Joel S.; Perou, Charles M.; Roach, Jeffrey; Schein, Jacqueline E.; Schumacher, Steven E.; Shi, Yan; Simons, Janae V.; Sipahimalani, Payal; Skelly, Tara; Soloway, Matthew G.; Sougnez, Carrie; Tam, Angela; Tan, Donghui; Thiessen, Nina; Veluvolu, Umadevi; Wang, Min; Wilkerson, Matthew D.; Wong, Tina; Wu, Junyuan; Xi, Liu; Zhou, Jane; Bedford, Jason; Chen, Fengju; Fu, Yao; Gerstein, Mark; Haussler, David; Kasaian, Katayoon; Lai, Phillip; Ling, Shiyun; Radenbaugh, Amie; Van Den Berg, David; Weinstein, John N.; Zhu, Jingchun; Albert, Monique; Alexopoulou, Iakovina; Andersen, Jeremiah J; Auman, J. Todd; Bartlett, John; Bastacky, Sheldon; Bergsten, Julie; Blute, Michael L.; Boice, Lori; Bollag, Roni J.; Boyd, Jeff; Castle, Erik; Chen, Ying-Bei; Cheville, John C.; Curley, Erin; Davies, Benjamin; DeVolk, April; Dhir, Rajiv; Dike, Laura; Eckman, John; Engel, Jay; Harr, Jodi; Hrebinko, Ronald; Huang, Mei; Huelsenbeck-Dill, Lori; Iacocca, Mary; Jacobs, Bruce; Lobis, Michael; Maranchie, Jodi K.; McMeekin, Scott; Myers, Jerome; Nelson, Joel; Parfitt, Jeremy; Parwani, Anil; Petrelli, Nicholas; Rabeno, Brenda; Roy, Somak; Salner, Andrew L.; Slaton, Joel; Stanton, Melissa; Thompson, R. Houston; Thorne, Leigh; Tucker, Kelinda; Weinberger, Paul M.; Winemiller, Cythnia; Zach, Leigh Anne; Zuna, Rosemary

    2016-01-01

    Background Papillary renal cell carcinoma, accounting for 15% of renal cell carcinoma, is a heterogeneous disease consisting of different types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal cell carcinoma; no effective forms of therapy for advanced disease exist. Methods We performed comprehensive molecular characterization utilizing whole-exome sequencing, copy number, mRNA, microRNA, methylation and proteomic analyses of 161 primary papillary renal cell carcinomas. Results Type 1 and Type 2 papillary renal cell carcinomas were found to be different types of renal cancer characterized by specific genetic alterations, with Type 2 further classified into three individual subgroups based on molecular differences that influenced patient survival. MET alterations were associated with Type 1 tumors, whereas Type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-ARE pathway. A CpG island methylator phenotype (CIMP) was found in a distinct subset of Type 2 papillary renal cell carcinoma characterized by poor survival and mutation of the fumarate hydratase (FH) gene. Conclusions Type 1 and Type 2 papillary renal cell carcinomas are clinically and biologically distinct. Alterations in the MET pathway are associated with Type 1 and activation of the NRF2-ARE pathway with Type 2; CDKN2A loss and CIMP in Type 2 convey a poor prognosis. Furthermore, Type 2 papillary renal cell carcinoma consists of at least 3 subtypes based upon molecular and phenotypic features. PMID:26536169

  19. Parotid carcinoma

    DEFF Research Database (Denmark)

    Godballe, Christian; Schultz, Joyce H; Krogdahl, Annelise

    2003-01-01

    Hospital (Odense, Denmark) from 1975 to 1994. METHODS: Patient records were retrospectively reviewed and tabulated for relevant clinical parameters. A complete revision of histological examination was performed by the same pathologist and the tumors were classified according to the 1991 international...... guidelines from the World Health Organization. Five tumors (6%) did not fulfill the criteria of malignancy and were reclassified as benign. In another five cases the assumed primary parotid carcinomas were found to be metastatic disease from cancers of the breast, prostate, skin, and lungs. Ten patients (12......-year recurrence-free survival of the entire study group was 63%, disease-specific survival was 69%, and crude survival was 52%. In univariate analysis, tumor size, histological appearance, T status, stage, the presence of lymph node metastases, distant metastases, pain, and facial nerve dysfunction had...

  20. Giant basal cell carcinoma Carcinoma basocelular gigante

    Directory of Open Access Journals (Sweden)

    Nilton Nasser

    2012-06-01

    Full Text Available The basal cell carcinoma is the most common skin cancer but the giant vegetating basal cell carcinoma reaches less than 0.5 % of all basal cell carcinoma types. The Giant BCC, defined as a lesion with more than 5 cm at its largest diameter, is a rare form of BCC and commonly occurs on the trunk. This patient, male, 42 years old presents a Giant Basal Cell Carcinoma which reaches 180 cm2 on the right shoulder and was negligent in looking for treatment. Surgical treatment was performed and no signs of dissemination or local recurrence have been detected after follow up of five years.O carcinoma basocelular é o tipo mais comum de câncer de pele, mas o carcinoma basocelular gigante vegetante não atinge 0,5% de todos os tipos de carcinomas basocelulares. O Carcinoma Basocelular Gigante, definido como lesão maior que 5 cm no maior diâmetro, é uma forma rara de carcinoma basocelular e comumente ocorre no tronco. Este paciente apresenta um Carcinoma Basocelular Gigante com 180cm² no ombro direito e foi negligente em procurar tratamento. Foi realizado tratamento cirúrgico e nenhum sinal de disseminação ou recorrência local foi detectada após 5 anos.

  1. Robotic adrenalectomy for sigmoid colon cancer oligometastasis.

    Science.gov (United States)

    Pai, Vishwas D; Bhandare, Manish; Deodhar, Kedar; Yuvaraja, Thyavihally Boregowda; Saklani, Avanish P

    2015-12-01

    Solitary adrenal metastasis from colorectal cancer is rare with reported incidence from 3.1% to 14.4% in the literature. Conventionally, adrenal metastasis is considered as indicative of widespread systemic disease and hence treated with palliative intent. Surgical resection remains controversial although a median survival of 32 months was found in the largest reported case series. It has been postulated that surgical resection should be offered when the adrenal metastasis develops more than 6 months after the treatment of the primary tumor. For the metastatic lesions and potentially malignant lesions, role of minimally invasive surgery is still considered controversial. We are presenting a case of metachronous, solitary adrenal metastasis from sigmoid colon carcinoma treated surgically with curative intent.

  2. [Role of CT/111In-octreotide SPECT digital fusion imaging in the localization of loco-regional recurrence of medullary thyroid carcinoma

    NARCIS (Netherlands)

    Fiore, D.; Rubello, D.; Casara, D.; Pelizzo, M.R.; Franchi, A.; Muzzio, P.C.

    2004-01-01

    The case of a female patient affected by a sporadic medullary thyroid carcinoma (pT1N1aM0 at the onset) is reported. The patient had been initially treated by total thyroidectomy and lymphadenectomy of the central and lateral portions of the neck. During the following 30 years of follow-up, the

  3. Colonization, mouse-style

    Directory of Open Access Journals (Sweden)

    Searle Jeremy B

    2010-10-01

    Full Text Available Abstract Several recent papers, including one in BMC Evolutionary Biology, examine the colonization history of house mice. As well as background for the analysis of mouse adaptation, such studies offer a perspective on the history of movements of the humans that accidentally transported the mice. See research article: http://www.biomedcentral.com/1471-2148/10/325

  4. Helical CT pneumocolon to assess colonic tumors: radiologic-pathologic correlation.

    Science.gov (United States)

    Harvey, C J; Amin, Z; Hare, C M; Gillams, A R; Novelli, M R; Boulos, P B; Lees, W R

    1998-06-01

    The objective of this study was to determine the accuracy of helical CT pneumocolon in the staging of colonic carcinomas. Fifty-two patients (27 men, 25 women; age range, 40-88 years old; mean age, 67 years old) with known or strongly suspected colonic disorders underwent CT pneumocolon. After bowel cleansing, administration of smooth muscle relaxant, and rectal air insufflation, CT pneumocolon was performed with 5-mm collimation, 2.5-mm reconstruction interval, and a pitch of 1.5. Two contrast administration protocols were used. Twelve patients received 100 ml of i.v. contrast material that was injected at 3 ml/sec; scan delay was 45 sec. The other 40 patients received 150 ml of contrast material at 5 ml/sec; scan delay was 25 sec. Images were prospectively evaluated. All patients had pathologic confirmation: 46 patients had resections and six patients had endoscopic biopsies. Diagnostic images were obtained in 47 of 52 patients. In the 47 patients, there were 38 colonic carcinomas (one synchronous), nine diverticular strictures, eight polyps, one ischemic stricture, and one normal study. Thirty of 38 carcinomas were correctly staged by CT. Sensitivity and specificity for serosal infiltration were 100% (35/35 carcinomas) and 33% (one of three carcinomas), respectively; sensitivity and specificity for lymph node involvement were 56% (nine of 16 carcinomas) and 95% (21/22 carcinomas), respectively. Four polyps that were smaller than 5 mm in diameter were not revealed by CT. Twelve of 14 benign lesions were correctly diagnosed and two were believed to be malignant. No malignant lesion was misdiagnosed. CT pneumocolon gave an overall staging accuracy of 79% in 38 carcinomas.

  5. Oncogenic KRAS activates an embryonic stem cell-like program in human colon cancer initiation.

    Science.gov (United States)

    Le Rolle, Anne-France; Chiu, Thang K; Zeng, Zhaoshi; Shia, Jinru; Weiser, Martin R; Paty, Philip B; Chiu, Vi K

    2016-01-19

    Colorectal cancer is the third most frequently diagnosed cancer worldwide. Prevention of colorectal cancer initiation represents the most effective overall strategy to reduce its associated morbidity and mortality. Activating KRAS mutation (KRASmut) is the most prevalent oncogenic driver in colorectal cancer development, and KRASmut inhibition represents an unmet clinical need. We apply a systems-level approach to study the impact of KRASmut on stem cell signaling during human colon cancer initiation by performing gene set enrichment analysis on gene expression from human colon tissues. We find that KRASmut imposes the embryonic stem cell-like program during human colon cancer initiation from colon adenoma to stage I carcinoma. Expression of miR145, an embryonic SC program inhibitor, promotes cell lineage differentiation marker expression in KRASmut colon cancer cells and significantly suppresses their tumorigenicity. Our data support an in vivo plasticity model of human colon cancer initiation that merges the intrinsic stem cell properties of aberrant colon stem cells with the embryonic stem cell-like program induced by KRASmut to optimize malignant transformation. Inhibition of the embryonic SC-like program in KRASmut colon cancer cells reveals a novel therapeutic strategy to programmatically inhibit KRASmut tumors and prevent colon cancer.

  6. Clinical Perspective of Oxidative Stress in Sporadic ALS

    Science.gov (United States)

    D’Amico, Emanuele; Factor-Litvak, Pam; Santella, Regina M.; Mitsumoto, Hiroshi

    2013-01-01

    Sporadic amyotrophic lateral sclerosis (sALS) is one of the most devastating neurological diseases; most patients die within 3 to 4 years after symptom onset. Oxidative stress is a disturbance in the pro-oxidative/anti-oxidative balance favoring the pro-oxidative state. Autopsy and laboratory studies in ALS indicate that oxidative stress plays a major role in motor neuron degeneration and astrocyte dysfunction. Oxidative stress biomarkers in cerebrospinal fluid, plasma, and urine, are elevated, suggesting that abnormal oxidative stress is generated outside of the central nervous system. Our review indicates that agricultural chemicals, heavy metals, military service, professional sports, excessive physical exertion, chronic head trauma, and certain foods might be modestly associated with ALS risk, with a stronger association between risk and smoking. At the cellular level, these factors are all involved in generating oxidative stress. Experimental studies indicate that a combination of insults that induce modest oxidative stress can exert additive deleterious effects on motor neurons, suggesting multiple exposures in real-world environments are important. As the disease progresses, nutritional deficiency, cachexia, psychological stress, and impending respiratory failure may further increase oxidative stress. Moreover, accumulating evidence suggests that ALS is possibly a systemic disease. Laboratory, pathologic, and epidemiologic evidence clearly support the hypothesis that oxidative stress is central in the pathogenic process, particularly in genetically susceptive individuals. If we are to improve ALS treatment, well-designed biochemical and genetic epidemiological studies, combined with a multidisciplinary research approach, are needed and will provide knowledge crucial to our understanding of ALS etiology, pathophysiology, and prognosis. PMID:23797033

  7. Upregulated Genes In Sporadic, Idiopathic Pulmonary Arterial Hypertension

    Directory of Open Access Journals (Sweden)

    Yacoub Magdi H

    2006-01-01

    Full Text Available Abstract Background To elucidate further the pathogenesis of sporadic, idiopathic pulmonary arterial hypertension (IPAH and identify potential therapeutic avenues, differential gene expression in IPAH was examined by suppression subtractive hybridisation (SSH. Methods Peripheral lung samples were obtained immediately after removal from patients undergoing lung transplant for IPAH without familial disease, and control tissues consisted of similarly sampled pieces of donor lungs not utilised during transplantation. Pools of lung mRNA from IPAH cases containing plexiform lesions and normal donor lungs were used to generate the tester and driver cDNA libraries, respectively. A subtracted IPAH cDNA library was made by SSH. Clones isolated from this subtracted library were examined for up regulated expression in IPAH using dot blot arrays of positive colony PCR products using both pooled cDNA libraries as probes. Clones verified as being upregulated were sequenced. For two genes the increase in expression was verified by northern blotting and data analysed using Student's unpaired two-tailed t-test. Results We present preliminary findings concerning candidate genes upregulated in IPAH. Twenty-seven upregulated genes were identified out of 192 clones examined. Upregulation in individual cases of IPAH was shown by northern blot for tissue inhibitor of metalloproteinase-3 and decorin (P Conclusion Four of the up regulated genes, magic roundabout, hevin, thrombomodulin and sucrose non-fermenting protein-related kinase-1 are expressed specifically by endothelial cells and one, muscleblind-1, by muscle cells, suggesting that they may be associated with plexiform lesions and hypertrophic arterial wall remodelling, respectively.

  8. Chlamydia pecorum: fetal and placental lesions in sporadic caprine abortion.

    Science.gov (United States)

    Giannitti, Federico; Anderson, Mark; Miller, Myrna; Rowe, Joan; Sverlow, Karen; Vasquez, Marce; Cantón, Germán

    2016-03-01

    Chlamydial abortion in small ruminants is usually associated with Chlamydia abortus infection. Although Chlamydia pecorum has been detected in aborted ruminants and epidemiological data suggests that C. pecorum is abortigenic in these species, published descriptions of lesions in fetuses are lacking. This work describes fetoplacental lesions in a caprine abortion with C. pecorum infection, and further supports the abortigenic role of C. pecorum in ruminants. A 16-month-old Boer goat aborted twin fetuses at ~130 days of gestation. Both fetuses (A and B) and the placenta of fetus A were submitted for postmortem examination and diagnostic workup. At autopsy, the fetuses had moderate anasarca, intermuscular edema in the hindquarters (A), and brachygnathia and palatoschisis (B). In the placenta, the cotyledons were covered by yellow fibrinosuppurative exudate that extended into the adjacent intercotyledonary areas. Histologically, there was severe suppurative and necrotizing placentitis with vasculitis (arteriolitis) and thrombosis, multifocal lymphohistiocytic and neutrophilic hepatitis (A), and fibrinosuppurative enteritis in both fetuses. Chlamydia antigen was detected in the placenta by the direct fluorescent antibody test and in fetal intestines by immunohistochemistry. Nested polymerase chain reaction of DNA extracted from formalin-fixed, paraffin-embedded sections of placenta and intestine amplified 400 bp of the Chlamydia 16S rRNA gene that was sequenced and found to be 99% identical to C. pecorum by BLAST analysis. Other known abortigenic infectious agents were ruled out by specific testing. It is concluded that C. pecorum infection is associated with fetoplacental lesions and sporadic abortion in goats. © 2015 The Author(s).

  9. Genotype and phenotype analysis of patients with sporadic periodic paralysis.

    Science.gov (United States)

    Sung, Chih-Chien; Cheng, Chih-Jen; Lo, Yi-Fen; Lin, Mei-Shan; Yang, Sung-Sen; Hsu, Yu-Chuan; Lin, Shih-Hua

    2012-04-01

    Sporadic periodic paralysis (SPP), the second leading cause of hypokalemic periodic paralysis (HPP) in Asia, has a presentation similar to that of familial periodic paralysis (FPP) and is caused by gene mutations in the calcium (Ca(2+)) (CACNA1S) and sodium (Na(+)) (SCN4A) channels of skeletal muscle. The authors determined whether SPP shares similar genotype and phenotype with FPP. Sixty SPP patients who did not have a family history of paralysis, abnormal thyroid function tests and other identifiable causes of HPP, and 8 FPP patients were enrolled. Genomic DNA was isolated from blood leukocytes of all SPP and FPP patients. Genetic analysis of whole S4 segment in CACNA1S and SCN4A was performed. Phenotypic analysis included clinical presentations, laboratory data and precipitating events. All FPP patients had mutations in either CACNA1S or SCN4A, but only 4 SPP patients had de novo mutations in CACNA1S (R1239H) and SCN4A (R669×2, R1135H). SPP patients with de novo mutations manifested a phenotype indistinguishable from that of FPP patients except a later age of onset. SPP patients without mutations also had a later age of onset, significantly fewer attacks of paralysis than FPP patients, and unidentifiable precipitating factors. A minority of SPP patients had de novo CACNA1S or SCN4A mutations and may have a variant of FPP. The majority of SPP patients, those without mutations in CACNA1S and SCN4A, represent a unique subgroup of HPP patients, and this form of SPP usually manifests at a later age, is associated with fewer attacks and lacks apparent triggering factors.

  10. Identification of epigenetically altered genes in sporadic amyotrophic lateral sclerosis.

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    Claudia Figueroa-Romero

    Full Text Available Amyotrophic lateral sclerosis (ALS is a terminal disease involving the progressive degeneration of motor neurons within the motor cortex, brainstem and spinal cord. Most cases are sporadic (sALS with unknown causes suggesting that the etiology of sALS may not be limited to the genotype of patients, but may be influenced by exposure to environmental factors. Alterations in epigenetic modifications are likely to play a role in disease onset and progression in ALS, as aberrant epigenetic patterns may be acquired throughout life. The aim of this study was to identify epigenetic marks associated with sALS. We hypothesize that epigenetic modifications may alter the expression of pathogenesis-related genes leading to the onset and progression of sALS. Using ELISA assays, we observed alterations in global methylation (5 mC and hydroxymethylation (5 HmC in postmortem sALS spinal cord but not in whole blood. Loci-specific differentially methylated and expressed genes in sALS spinal cord were identified by genome-wide 5mC and expression profiling using high-throughput microarrays. Concordant direction, hyper- or hypo-5mC with parallel changes in gene expression (under- or over-expression, was observed in 112 genes highly associated with biological functions related to immune and inflammation response. Furthermore, literature-based analysis identified potential associations among the epigenes. Integration of methylomics and transcriptomics data successfully revealed methylation changes in sALS spinal cord. This study represents an initial identification of epigenetic regulatory mechanisms in sALS which may improve our understanding of sALS pathogenesis for the identification of biomarkers and new therapeutic targets.

  11. Geographical and seasonal correlation of multiple sclerosis to sporadic schizophrenia

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    Fritzsche Markus

    2002-12-01

    Full Text Available Abstract Background Clusters by season and locality reveal a striking epidemiological overlap between sporadic schizophrenia and multiple sclerosis (MS. As the birth excesses of those individuals who later in life develop schizophrenia mirror the seasonal distribution of Ixodid ticks, a meta analysis has been performed between all neuropsychiatric birth excesses including MS and the epidemiology of spirochaetal infectious diseases. Results The prevalence of MS and schizophrenic birth excesses entirely spares the tropical belt where human treponematoses are endemic, whereas in more temperate climates infection rates of Borrelia garinii in ticks collected from seabirds match the global geographic distribution of MS. If the seasonal fluctuations of Lyme borreliosis in Europe are taken into account, the birth excesses of MS and those of schizophrenia are nine months apart, reflecting the activity of Ixodes ricinus at the time of embryonic implantation and birth. In America, this nine months' shift between MS and schizophrenic births is also reflected by the periodicity of Borrelia burgdorferi transmitting Ixodes pacificus ticks along the West Coast and the periodicity of Ixodes scapularis along the East Coast. With respect to Ixodid tick activity, amongst the neuropsychiatric birth excesses only amyotrophic lateral sclerosis (ALS shows a similar seasonal trend. Conclusion It cannot be excluded at present that maternal infection by Borrelia burgdorferi poses a risk to the unborn. The seasonal and geographical overlap between schizophrenia, MS and neuroborreliosis rather emphasises a causal relation that derives from exposure to a flagellar virulence factor at conception and delivery. It is hoped that the pathogenic correlation of spirochaetal virulence to temperature and heat shock proteins (HSP might encourage a new direction of research in molecular epidemiology.

  12. Schwannoma of the Colon

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    Ronaldo Nonose

    2009-09-01

    Full Text Available Schwannomas are neoplasms originating from Schwann cells, which are the cells forming nerve sheaths. These neoplasms generally involve peripheral nerves. They rarely affect the gastrointestinal tract and primary colon involvement is extremely rare. The objective of the present paper was to present a case of primary schwannoma of the sigmoid colon, unassociated with von Recklinghausen disease, that was histopathologically confirmed by means of an immunohistochemical panel. The patient was a 71-year-old woman who had had rectal bleeding when evacuating, with pain and tenesmus, for 4 months. She underwent colonoscopy, which identified a raised submucous les