Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Japanese men in Hawaii whose ancestral roots were in Okinawa were compared to Japanese migrants from all other prefectures. The Okinawan migrants have acquired fewer cancers than men from other prefectures (P = 0.12). No one primary site accounts for this difference. Stomach cancer rates showed the largest difference between the two migrant groups. This replicates the experience of Okinawans and non-Okinawans in Japan itself. Lymphosarcoma mortality rates are much higher in Okinawa than in all Japan, but this difference is not reproduced in Hawaiian migrants. This could be explained by a post migrational decrease in HTLV-I-related acute T-cell lymphoma/leukemia. Cancer of the mouth, pharynx and esophagus has decreased in all Japanese migrants, but the decrease is much greater among Okinawan migrants, suggesting they have escaped exposure to risk factors peculiar to the Okinawan environment. Colon cancer is more common in migrant Japanese than in U.S. whites. The dramatic increase in the frequency of this tumor affects Okinawan and non-Okinawan migrants to an equal degree.
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PMID:Cancer incidence in Hawaiian Japanese: migrants from Okinawa compared with those from other prefectures. 177 59

A 77-year-old man was admitted to our hospital, due to systemic lymph node swelling. Nine months before his admission, he had been given a right hemicolonectomy for a colon cancer, that had been followed by chemotherapy (MMC and Tegafur). Laboratory testing revealed these findings: RBC 217 x 10(4)/mm3, Hb 8.3 g/dl, haptoglobin less than 10 mg/dl, positive Coombs test, cold hemagglutinin titer, 1:512, and polyclonal hyper r-globulinemia. A biopsy of a lymph node specimen exhibited the histological appearance of an IBL-like T-cell lymphoma described by Shimoyama et al. Although treatment with prednisolone was started for autoimmune hemolytic anemia, the patient died of severe anemia two months after the appearance of his lymph node symptoms.
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PMID:[An autopsy study of immunoblastic lymphadenopathy (IBL)-like T-cell lymphoma in a patient previously treated with chemotherapy in colon cancer]. 249 73

Hereditary non-polyposis colon cancer (HNPCC) is an autosomal dominant disorder featuring familial clustering of colorectal and/or endometrial cancer, and other malignancies. Except for a rare case report, Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) have not been considered part of HNPCC. Recent murine models for HNPCC have shown an increased incidence of B- and T-cell lymphoma, as well as tumors of the gastrointestinal tract and other organ systems, involving defects in genes resulting in faulty mismatch repair (MMR) of DNA. These MMR genes include MLH1, MSH2, MSH3, MSH6, PMS1 and PMS2. We sought to analyze the occurrence of NHL and HD in families with clusters of colorectal cancers (CRC). Probands from 21 kindreds were classified as HNPCC (3), HNPCC-like (5), and HNPCC-variant (13); seen and followed by Clinical Genetics at Memorial Hospital the kindreds were assessed for the occurrence of NHL or HD. Of the 21 pedigrees, a total of 37 patients were identified who were diagnosed with leukemia, lymphoma, or HD. Fourteen of the 37 patients with a diagnosis of NHL or HD were further classified and showed varying histologies ranging from chronic lymphocytic leukemia/small lymphocytic lymphoma (2), mycosis fungoides (1), follicular lymphoma (1), extranodal marginal zone lymphoma of MALT type (2), diffuse large B-cell lymphoma (4), nodular sclerosis HD (3), and mixed cellularity HD (1). Microsatellite instability studies were performed on 6 cases but none showed evidence of replication error repair defects. Immunohistochemical stains performed on paraffin sections from these 6 representative cases showed differential protein expression of MLH1, MSH2, MSH6, and PMS2 when compared to normal reactive tissues from the same patient but showed no significant differences when compared to controls of non-familial, sporadic lymphomas. These results suggest that lymphomas arising in the setting of familial CRC do not bear the molecular hallmarks of HNPCC. Further studies are needed to explain the differential patterns of expression of RER-associated proteins in lymphomas, as well as the association of lymphomas and possibly renal cell cancers in a subset of kindreds in which CRC clustering is evident.
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PMID:Analysis of mismatch repair defects in the familial occurrence of lymphoma and colorectal cancer. 1240 Jun 5

A 69-year-old man underwent right hemicolectomy for colon cancer in the transverse colon in 2005. Two years after surgery, he was admitted with abdominal pain. Colonoscopy revealed a submucosal tumor of approximately 4 cm in size at the ileocolonic anastomosis site. In the biopsied samples from the anastomosis site, there was diffuse proliferation of large lymphoid cells, which were immunohistochemically positive for CD3 and CD4, but negative for CD8 and CD20. Clonality analysis of T-cell receptor-beta gene rearrangement revealed a single band, indicating monoclonal proliferation of the T- lymphocytes. Epstein-Barr virus in situ hybridization did not reveal any positive signals in any of the tumor cells. Anti-human T-lymphotropic virus-I was negative. Based on these findings, the recurrent tumor was diagnosed as peripheral T-cell lymphoma-unspecified (PTCL-u).
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PMID:Peripheral T-cell lymphoma developing at ileocolonic anastomosis site after colectomy for adenocarcinoma. 1983 49

Colorectal cancer is the third most common malignancy in Korea. In contrast, pericolic or mesenteric lymphoma is relatively rare. We experienced an extremely rare case of synchronous primary colon cancer in the ascending colon with T-cell lymphoma in the pericolic lymph node. A 79-year-old woman presented with complaints of epigastric and right lower abdominal pain combined with anorexia and nausea. Colonoscopic evaluation and biopsy were performed, and the diagnosis was cecal adenocarcinoma. She underwent right hemicolectomy with lymph node dissection. The pathology report revealed adenocarcinoma in cecum with metastasis to 1 regional lymph node out of 37 lymph nodes. In addition, there was malignant angioimmunoblastic T-cell lymphoma in 1 pericolic lymph node. There was no evidence of lymphoma in ileum, cecum and ascending colon, so the possibility of early phase of lymphoma was suggested.
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PMID:Synchronous T-cell lymphoma in patient with colon cancer: a case report. 2279 36

Extranodal natural killer/T-cell lymphoma (ENKTL) is a distinct subtype of non-Hodgkin's lymphoma and is rare in the colon. Synchronous adenocarcinoma and ENKTL of the colon has not been reported in the literature. In the present study, we report a 63-year-old male who suffered from intermittent bloody stools for 2 mo. He did not have fever, body weight loss or night sweat. Endoscopic and imaging studies revealed a 4.5-cm ulcerative mass in the ascending colon and a 3.0-cm polypoid, easy bleeding mass in the sigmoid colon, respectively. Thought to have double carcinoma of the colon, he received simultaneous right hemicolectomy and sigmoidectomy. The pathological diagnosis was a synchronous ENKTL (ascending colon) and adenocarcinoma (sigmoid colon). The literature on synchronous adenocarcinoma and malignant lymphoma of the colon was also reviewed.
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PMID:Synchronous adenocarcinoma and extranodal natural killer/T-cell lymphoma of the colon: a case report and literature review. 2355 76

Activation of human pregnane X receptor (hPXR) has been associated with induction of chemoresistance. It has been proposed that such chemoresistance via cytochrome P450/drug transporters can be reversed with the use of antagonists that specifically abrogate agonist-mediated hPXR activation. Unfortunately, proposed antagonists lack the specificity and appropriate pharmacological characteristics that allow these features to be active in the clinic. We propose that, ideally, an hPXR antagonist would be a cancer drug itself that is part of a "cancer drug cocktail" and effective as an hPXR antagonist at therapeutic concentrations. Belinostat (BEL), a histone deacetylase inhibitor approved for the treatment of relapsed/refractory peripheral T-cell lymphoma, and often used in combination with chemotherapy, is an attractive candidate based on its hPXR ligand-like features. We sought to determine whether these features of BEL might allow it to behave as an antagonist in combination chemotherapy regimens that include hPXR activators. BEL represses agonist-activated hPXR target gene expression at its therapeutic concentrations in human primary hepatocytes and LS174T human colon cancer cells. BEL repressed rifampicin-induced gene expression of CYP3A4 and multidrug resistance protein 1, as well as their respective protein activities. BEL decreased rifampicin-induced resistance to SN-38, the active metabolite of irinotecan, in LS174T cells. This finding indicates that BEL could suppress hPXR agonist-induced chemoresistance. BEL attenuated the agonist-induced steroid receptor coactivator-1 interaction with hPXR, and, together with molecular docking studies, the study suggests that BEL directly interacts with multiple sites on hPXR. Taken together, our results suggest that BEL, at its clinically relevant therapeutic concentration, can antagonize hPXR agonist-induced gene expression and chemoresistance.
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PMID:Belinostat, at Its Clinically Relevant Concentrations, Inhibits Rifampicin-Induced CYP3A4 and MDR1 Gene Expression. 3062 15

Histone deacetylases (HDACs) play important roles in various biological processes, but are also notorious for their over-expression in numerous cancers and neurological disorders. Therefore, the development of isoform selective HDAC inhibitors is crucial in order to prevent any side effects of pan inhibition. This work focuses on identifying novel inhibitors for the selective inhibition of HDAC8, an isoform implicated in fatal diseases like T-cell lymphoma, colon cancer and childhood neuroblastoma. Virtual screening of the 'In-trials' subset of ZINC database has been carried out with the help of two pharmacophore models signifying potent and selective HDAC8 inhibition. A detailed molecular docking strategy, followed by molecular dynamics simulations and post-scoring with MM-GBSA calculations, has led to the identification of six promising molecules that have excellent binding with the HDAC8 active site. In order to establish the selectivity profile of these molecules, their binding to off-target HDAC isoforms has also been evaluated. Substitution analyses of the proposed inhibitors suggest that aromatic substituents that access the adjacent hydrophobic pocket of the HDAC8 active site have the potential to further enhance the HDAC8 selectivity.
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PMID:Pharmacophore-enabled virtual screening, molecular docking and molecular dynamics studies for identification of potent and selective histone deacetylase 8 inhibitors. 3265 83