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)

Double-label immunofluorescence was used to monitor basement-membrane composition and integrity in 22 human colon polyps, 36 adenocarcinomas and 2 metastases. Cryostat sections were stained with polyclonal anti-laminin anti-serum combined with monoclonal antibodies (MAbs) to all major basement-membrane components (laminin, entactin/nidogen, collagen type IV and large heparan sulfate proteoglycan), as well as to keratin 8. In all adenocarcinomas, including mucinous, basement membranes were altered more at the invasive front than in the parenchyma. The degree of this alteration was inversely correlated with the level of tumor differentiation. An uncoordinated loss of basement membrane components (dissociation of markers), previously described by us in rat colon adenocarcinomas, was also found in human tumors. In the great majority of adenocarcinomas a pronounced stromal reaction was seen. It was manifested by the presence of fibrillar deposits of basement-membrane components, mainly of collagen type IV and/or heparan sulfate proteoglycan. This reaction was never observed in polyps and may be derived from myofibroblasts reported to accumulate in colon cancer stroma. The combined use of antibodies to basement-membrane components and to a specific keratin may constitute an adequate immunohistochemical test for the presence of invasion, and may be useful in the histologic analysis of polyps, especially in dubious cases.
 ...
PMID:Distribution of individual components of basement membrane in human colon polyps and adenocarcinomas as revealed by monoclonal antibodies. 137

Dietary cooked casein promotes colon cancer in rats. We speculated and tested the hypothesis that cooking reduces the digestibility of casein, and increases the yield of bacterial metabolites, which are potential promoters of cancer. We investigated dietary means to manipulate nitrogen transfer and fermentation in the caecum. The caecal digestion of casein (cooked or not), keratin (hydrolysed or not) and bovine serum albumin (oxidized or not) was measured in rats. Protein fermentation was estimated by assaying caecal ammonia and branched-chain fatty acids. Keratin and cooked casein were digested to a very low extent, and were poorly fermented. Rats given cooked casein had 2-3 times more ammonia in their caecum than animals given the other proteins. Antibiotics (bacitracin, chlortetracycline, neomycin and spiramycin, at either 20 and 80 micrograms/ml water) decreased caecal ammonia in rats eating cooked casein, with spiramycin being most efficient. These data support the hypothesis given above, and provide ways to manipulate caecal ammonia.
 ...
PMID:Digestion and fermentation of proteins in rats fed keratin, albumin, cooked casein and antibiotics. 751 Apr 93

Acantholytic foci have been reported several times in pityriasis rubra pilaris (PRP). Lichenoid tissue reactions were also mentioned in the literature regarding PRP. We report a 58-year-old patient who, after having colon cancer, had PRP with biopsies showing acantholytic lesions and a heavy lichenoid lymphocytic infiltration. Investigation by serial sectioning of the acantholytic lesion suggested an involvement of the intraepidermal eccrine duct and further investigation with carcinoembryonic antigen (CEA) staining demonstrated a CEA-positive eccrine duct in the acantholytic foci. We suggest that acantholysis in PRP is induced by proteolytic enzymes, urea, and other substances in eccrine sweat in keratin-plugged acrosyringia. This patient had a combination of three relatively rare features of PRP-acantholysis, lichenoid reaction, and a cancer background.
 ...
PMID:Pityriasis rubra pilaris with acantholysis and lichenoid histology. 1053 83

The differential expression of hundreds of tightly, transcriptionally controlled genes in isolated human colorectal cancer and respective normal mucosa from two patients was analyzed by the cDNA macroarray technique. mRNA prepared from the colorectal cancer tumors was compared with 588 genes spotted onto the filter. Case A showed down-regulation of the expression of cell-cycle-related genes including cyclins, cyclin-dependent kinase (CDK) 2, and CDK-activating kinase, as compared with normal mucosa from the same patient. The tumors showed up-regulation of expression of angiogenesis-related genes such as type II cytoskeletal 8 keratin, metalloproteinase subtypes, VEGF, and bFGF, to over 5-fold the levels in normal mucosa. Thus, colorectal carcinoma tissues are characterized by the upregulation of molecules related with angiogenesis. These results suggest that angiogenesis-related molecules are suitable candidates for target-based therapies for colorectal cancer patients. In case B, the largest difference in expression between the tumor and mucosal tissues was observed in the MMP-1 gene. In contrast to the first case, there was no increase in expression of angiogenesis-related molecules or decrease in expression of cell-cycle-regulatory molecules. The expression profile was quite different between these two patients. This approach may eventually provide a mean of selecting target-based drugs in individual colon cancer patients.
 ...
PMID:Upregulated expression of angiogenesis genes and down regulation of cell cycle genes in human colorectal cancer tissue determined by cDNA macroarray. 1129 27

Epidemiological and preclinical data indicate that vitamin D and its most active metabolite 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)] have anticancer activity. Accordingly, clinical trials are under way using several nonhypercalcemic 1alpha,25(OH)(2)D(3) analogues against various neoplasms including colon cancer. 1alpha,25(OH)(2)D(3) induces proliferation arrest and epithelial differentiation of human SW480-ADH colon cancer cells. We examined the gene expression profiles associated with 1alpha,25(OH)(2)D(3) exposure using oligonucleotide microarrays. 1alpha,25(OH)(2)D(3) changed the expression levels of numerous previously unreported genes, including many involved in transcription, cell adhesion, DNA synthesis, apoptosis, redox status, and intracellular signaling. Most genes were up-regulated, and only a small fraction were down-regulated. Fourteen of 17 candidate genes studied were validated as 1alpha,25(OH)(2)D(3) target genes by Northern and Western blotting or immunocytochemistry. They included c-JUN, JUNB, JUND, FREAC-1/FoxF1, ZNF-44/KOX7, plectin, filamin, keratin-13, G(0)S2, and the putative tumor suppressors NES-1 and protease M. There was little overlap between genes regulated after short (4 h) or long (48 h) exposure. Gene regulatory effects of 1alpha,25(OH)(2)D(3) in SW480-ADH cells differed from those in LS-174T cells, which lack E-cadherin and do not differentiate in response to 1alpha,25(OH)(2)D(3). Data from this study reveal that 1alpha,25(OH)(2)D(3) causes a profound change in gene expression profiles and provide a mechanistic basis to the ongoing clinical studies using nonhypercalcemic vitamin D(3) derivatives for colon cancer prevention and treatment.
 ...
PMID:Genetic signatures of differentiation induced by 1alpha,25-dihydroxyvitamin D3 in human colon cancer cells. 1463 6

Vimentin is a type III Intermediate filament protein that is expressed frequently in epithelial carcinomas correlating with invasiveness and poor prognosis. We have analysed migration and adhesion to collagenous matrix of a panel of carcinoma cell lines. In vitro invasiveness was highest in vimentin-positive SW480 colon cancer and MDA-MB-231 breast cancer cells and the role of vimentin in these cell lines was investigated by RNA interference. Down-regulation of vimentin expression resulted in impaired migration in both scratch-wound experiments and in invasion assays through cell culture inserts coated with collagen gel. Compromised migration was observed in both cell lines, whereas cell attachment assays revealed impaired adhesion to fibrillar collagen in MDA-MB-231 cells while the adhesion of vimentin-ablated SW480 cells, that express both vimentin and keratin intermediate filaments was not affected. In conclusion, ablation of vimentin expression inhibits migration and invasion of colon and breast cancer cell lines.
 ...
PMID:Down-regulation of vimentin expression inhibits carcinoma cell migration and adhesion. 1758 78

Basaloid squamous cell carcinoma is a rare and aggressive variant of squamous cell carcinoma, which mostly occurs in the upper aerodigestive tracts. Basaloid squamous cell carcinoma also typically arises in the anal canal, but is extremely rare in the lower gastrointestinal tract. A 70-year-old man presented with loose stool and intermittent hematochezia 2 months ago. Colonoscopy showed an ulceroinfiltrative mass on the rectosigmoid colon from 16 cm to 18 cm above the anal verge. Conventional colonoscope could not pass through the lesion but it was possible with pediatric colonoscope. Abdominal CT scan showed 1.6 cm sized wall thickening with circumferential luminal narrowing in the rectosigmoid colon and multiple ill-defined low density masses in both lobes of the liver. Therefore, colon cancer with liver metastasis was suspected. However, basaloid cells were noted on histologic examination, and they were weakly positive for synaptophysin on immunohistochemical study. After palliative lower anterior resection, histologic examination of the resected specimen revealed basaloid differentiation with keratin pearls, and tumor cells were positively stained with high molecular weighted cytokeratin (34BE12) and CK 5/6. Thus, the patient was finally diagnosed with basaloid squamous cell carcinoma of rectosigmoid colon with distant metastases.
 ...
PMID:[A case of basaloid squamous cell carcinoma of rectosigmoid colon]. 2436 38

Proteomic analysis using multiplex affinity reagents is perhaps the most reliable strategy to capture differentially expressed proteins that are slightly or immensely modified. In addition to expressional variation, it is comprehensively evident that the immunogenicity of a protein can be a deciding factor for instigating an inflammation afflicted-carcinogenesis. Considering both these factors, a simple and systematic strategy was designed to capture the immunogenic cancer biomarkers from sera of colorectal cancer patients. The affinity reagent, in the form of an antibody repertoire against the secretome of the HT29 cell line was used to grade the sera samples on the basis of the degree of immuno-reactivity and to capture differentially expressed antigens from the patient sera. Following affinity based 2DE-MALDI-TOF; the proteins were identified as (1) soluble vimentin; and (2) TGF-beta-inhibited membrane-associated protein (PP16B), in colon cancer sera and (3) keratin, type II cytoskeletal protein in rectal cancer sera. Pathway reconstruction and protein-protein networking of identified proteins predicted only Vimentin to be physically and genetically engaged in close proximity with the most established colorectal cancer associated tumorigenic pathways. Furthermore, our findings suggest that a possible surface stoichiometric shift in the structure of protein could be due to mutations in the coding sequence of Vimentin that may elicit its enhanced secretion possibly due to protein-hyperphosphorylation. Of the three proteins identified, only Vimentin showed higher expression in sera of colon cancer patients alone. Thus, it could be argued that vimentin might help in predicting individuals at higher risk of developing colon cancers. Our data are therefore suggestive of using vimentin as an antigen for tumor vaccination in an autologous set-up for colon cancers.
...
PMID:Affinity proteomics led identification of vimentin as a potential biomarker in colon cancers: insights from serological screening and computational modelling. 2531 51