Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gastric cancer involves changes in multiple oncogenes and multiple suppressor genes, and it causes genetic instability. Aberrant expression and amplification of the c-met gene, inactivation of the p53 gene, and CD44 abnormal transcripts are common events of both well differentiated and poorly differentiated gastric cancers. Amplification of the cyclin E gene is also observed in gastric cancer regardless of histologic type. Decreased expression of the pic1 (p21) gene occurs independent of the p53 mutations. In addition, K-ras mutations, c-erbB-2 gene amplification, loss of heterozygosity (LOH) and mutations of the APC gene, LOH of the bcl-2 gene, and LOH at the DCC locus are preferentially associated with well differentiated gastric cancer. Moreover, LOH on chromosome 1q is involved in the progression of well differentiated cancer. Precancerous lesions, including hyperplastic polyp, intestinal metaplasia, and adenoma, share genetic changes found in well differentiated cancers. Conversely, genetic instability may be involved in the first step of stomach carcinogenesis of the poorly differentiated type. Reduction or loss of cadherin and catenins, K-sam gene amplification, and c-met gene amplification are necessary for the development and progression of poorly differentiated or scirrhous carcinoma. Interaction between cell-adhesion molecules in the c-met expressed tumor cells and hepatocyte growth factor from stromal cells is implicated in the morphogenesis of two types of gastric cancer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Molecular biology of gastric cancer. 767 88

The AIDS-associated lymphomas represent a heterogeneous set of disease processes. The largest histologic subset of lymphomas is the large-cell lymphomas, which represent a spectrum of disease processes ranging from monomorphic monoclonal B-cell proliferations to very polymorphic and polyclonal mixtures of B cells, T cells and macrophages. The next most frequent class of systemic lymphoma are the small non-cleaved cell or Burkitt's-like lymphomas. These are relatively monomorphic, monoclonal malignant B-cell proliferations. The final subset of lymphomas, which are likely to become more common as the AIDS epidemic progresses, are the primary CNS lymphomas, which are expansions of EBV-immortalized B cells. The high incidence of tumor-associated EBV in the CNS lymphomas makes these lesions somewhat analogous to an opportunistic EBV infection. In HIV disease there is a long lag after infection before the appearance of clinical manifestations of impaired T-cell immunity. During this period, both appropriate B-cell proliferation in response to antigen (including the ubiquitous HIV) and abnormal B-cell proliferation (autoimmune, dysregulated) occur as the follicular architecture is disrupted by the virus and potential APC are exposed and/or infected with HIV. The destruction of FDC or the involution of their processes could interfere with the elimination by apoptosis of low-avidity B-cell clones. Antigen-competent B cells with pre-existing chromosomal translocations such as the t(8;14) (c-myc, IgH) would have a selective growth advantage in this setting. Figure 9 shows a schematic representation of prelymphomatous and lymphomagenic events as they are projected to occur. A similar pathogenetic scheme has been postulated for follicular B-cell lymphomas: PCR studies have demonstrated that a pool of t(14;18) (IgH;bcl-2) B-cells are present in lymph nodes featuring follicular hyperplasia. In response to antigen (the evidence favoring antigen drive is extensive hypersomatic mutation in sequences related to binding sites), B cells with the t(14;18) translocation have a selective advantage because the bcl-2 oncogene confers a resistance to apoptosis. Burkitt's lymphomas, particularly sporadic or HIV variants, fulfill at least the key criteria for antigen competence, mainly the presence of surface Ig. The c-myc-associated chromosomal translocational events are likely to occur early during the enzymatic machinations of gene rearrangement. Such B cells would be in the dysregulated cytokine and antigen milieu of HIV disease and ultimately could have a selective advantage. EBV infection of B cells probably requires activation and expression of the CD21 receptor. Furthermore, CD5+ B cells of CLL are refractory to EBV infection.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pathogenesis of AIDS lymphomas. 798 99

Gene changes in multiple oncogenes, multiple growth factors and multiple tumor-suppressor genes are observed in stomach cancer. Among them, those most commonly implicated in both well-differentiated adenocarcinoma and poorly differentiated adenocarcinoma are inactivation (mutations and allele loss) of the p53 gene, and activation (abnormal expression and amplification) of the c-met gene. Moreover, they occur at an early stage of stomach carcinogenesis. In addition, loss of heterozygosity (LOH) on chromosome 5q (APC locus) is frequently associated with well-differentiated adenocarcinoma. LOH on chromosome 18q (DCC locus) and LOH of the bcl-2 gene also are common events of well-differentiated adenocarcinoma. LOH on chromosomes 1q and 7q may be involved in the progression of well-differentiated adenocarcinoma. Conversely, the development of poorly differentiated adenocarcinoma, in addition to changes in p53 and c-met genes, requires reduction or dysfunction of cadherin. Overexpression of bcl-2 protein is observed in poorly differentiated adenocarcinoma or signet-ring cell carcinoma. Moreover, the K-sam gene is amplified preferentially in poorly differentiated adenocarcinoma of scirrhous carcinoma. K-sam amplification in scirrhous carcinoma often occurs independently of c-met gene amplification. LOH on chromosome 1p also is relatively common in poorly differentiated adenocarcinoma. Exceptionally, signet-ring cell carcinoma shares APC mutations. There are some differences in expression of the growth-factor/receptor system between well-differentiated adenocarcinoma and poorly differentiated adenocarcinoma. Moreover, interaction between cell-adhesion molecules in tumor cells expressing c-met and hepatocyte growth factor (HGF) from stromal cells is linked with morphogenesis of two histological types of stomach cancer. Intestinal metaplasia and adenoma of the stomach also contain p53 mutations and K-ras mutations or tpr-met rearrangement. Taken together, different genetic pathways of stomach carcinogenesis may exist for poorly differentiated and well-differentiated stomach cancers. Some of the latter may develop by a cumulative series of gene alterations similar to those of colorectal cancer.
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PMID:Molecular mechanism of stomach carcinogenesis. 844 Jul 43

In this study, we examined the molecular signals that control apoptosis in cloned CD4+ helper T cells. Resting T cells were highly resistant to spontaneous death in the absence of exogenous stress, and they expressed low levels of bcl-x protein and no detectable bcl-2. Upon exposure to gamma radiation, resting cells rapidly underwent apoptotic death. Incubation with IL-2 prevented this cell death and led to a large increase in bcl-2 protein expression and only a modest up-regulation in bcl-x. The combination of anti-CD3 and anti-CD28 mAbs was also effective in protecting the cells against radiation-induced apoptosis; however, this protection was associated predominantly with bcl-x up-regulation, and only a small induction of bcl-2 protein was observed. Finally, cyclosporin A blocked both IL-2 secretion and bcl-2 induction in response to CD3 plus CD28 stimulation, suggesting a role for endogenous lymphokine production in the induction of bcl-2. These data support a model in which memory T cells remain resistant to apoptosis because intermittent contact with Ag-bearing APC and IL-2R occupancy result in the expression of the life-proteins bcl-2 and bcl-x.
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PMID:Differential regulation of bcl-2 and bcl-x by CD3, CD28, and the IL-2 receptor in cloned CD4+ helper T cells. A model for the long-term survival of memory cells. 859 25

The cooked meat mutagen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) produces tumors at multiple sites in the F344 rat, including adenocarcinomas of the colon. In the present study, the development of IQ-induced colorectal tumors was shown to be accompanied by the progressive inhibition of programmed cell death. This was associated with increased expression of the antiapoptosis protein Bcl-2 and decreased expression of bax, a known activator of apoptosis. Carcinomas bearing high levels of bcl-2 expression exhibited low levels of p53, the tumor suppressor protein that in some circumstances has been shown to down-regulate bcl-2. Because they lack mutations in the genes commonly associated with increased cell proliferation (APC, Ki-ras, and p53) and show no evidence of microsatellite instability, IQ-induced colon tumors might arise via the deregulation of bcl-2 expression, leading to inhibition of programmed cell death.
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PMID:Inhibition of apoptosis in colon tumors induced in the rat by 2-amino-3-methylimidazo[4,5-f]quinoline. 881 12

Genetic instability, alterations of tumor suppressor genes as well as activation of oncogenes and aberrant expression of growth factor/receptor system found in human stomach carcinogenesis are overviewed. Aberrant expression and amplification of the c-met gene, inactivation of the p53 gene and amplification of the cyclin E gene are common events of both well differentiated and poorly differentiated gastric carcinomas. K-ras mutations, c-erbB2 gene amplification, loss of heterozygosity (LOH) and mutations of the APC, LOH of the bcl-2 gene and LOH at DCC locus are preferentially associated with well differentiated gastric cancer. On the other hand, microsatellite instability, reduction or loss of cadherin and catenins, K-sam and c-met gene amplification confer the development and progression of poorly differentiated or scirrhous gastric carcinomas. Interaction between cell-adhesion molecules in the c-met expressed cancer cells and hepatocyte growth factor from stromal cells is involved in morphogenesis of gastric cancer.
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PMID:[Multistep stomach carcinogenesis]. 892 Jun 75

Colorectal carcinoma is a major cause of death throughout the Western world. It is increasingly recognized that any reduction in mortality must be achieved through the detection and removal of early and precancerous lesions. The primary attention for such a preventive strategy has been the polypoid adenoma and surveillance studies have shown a significant reduction in the incidence of carcinoma through systematic polypectomy of suspicious lesions. A potential problem with such a program, however, is raised by reports from Japan that some carcinomas seem to arise without a precursor polypoid adenoma, that is de novo. Although the histopathologic findings in such reports seem to clearly support this idea, this concept is not widely accepted in the Western world. We undertook a series of immunohistochemical (p53, bcl-2, Mib-1, E-cadherin, CD44, Stromelysin-3), and microsatellite analysis studies (on 17p (p53), 18q (DCC), 5q (APC), 8p, 2p and 1p), on groups of de novo and ex adenoma carcinomas in order to see if differences between the two groups of lesions exist. The results of these studies demonstrate that de novo carcinomas share several phenotypic and genotypic features with ex adenoma carcinoma (similar CD44 in the carcinomas, similar rates of LOH at APC and DCC loci), but have significantly higher rates of LOH at 17p, p53 over-expression and ST-3 expression indicating that tumor progression in de novo carcinoma is accelerated. These findings should help clarify the concept of de novo carcinoma and contribute to wider recognition of this important clinicopathologic entity.
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PMID:[Are there differences between ex adenoma and de novo colorectal carcinomas?]. 1071 4

We report a case of cribriform-morular variant (C-MV) of papillary thyroid carcinoma (PTC) in a 27-year-old woman. In addition to conventional cytologic features of typical PTC, the fine-needle aspirate showed numerous epithelial cells with abundant, eosinophilic, very elongated cytoplasm. Microscopically, the tumor was encapsulated and highly cellular and exhibited a mixture of cribriform, follicular, papillary, trabecular, solid, and spindle cell patterns of growth, with morular foci showing peculiar nuclear clearing (biotin-rich nuclei). The cells were cuboidal or tall, with frequent nuclear pseudostratification and abundant eosinophilic cytoplasm. The nuclei were usually hyperchromatic, with grooving, pallor, and pseudoinclusions. Angioinvasion and foci of capsular invasion were observed. Immunohistochemically, the neoplastic cells showed reactivity for thyroglobulin, epithelial membrane antigen, low- and high-molecular-weight cytokeratins, vimentin, neuron-specific enolase, CD15, estrogen and progesterone receptors, and bcl-2 protein. Molecular genetic analysis of the APC gene revealed a mutation in exon 15 at codon 1309 in tumoral tissue but not in peripheral lymphocytes. These findings support a relationship between the morphologic pattern of the C-MV of PTC and the APC gene and the existence of this variant as a sporadic counterpart of familial adenomatous polyposis-associated thyroid carcinoma.
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PMID:Somatic but not germline mutation of the APC gene in a case of cribriform-morular variant of papillary thyroid carcinoma. 1129 95

Epidemiologic studies have documented a 40-50% reduction in incidence of colorectal cancer in individuals taking nonsteroidal antiinflammatory drugs (NSAIDs). Since NSAIDs are known to inhibit cyclooxygenases (COX-1, COX-2), the basic mechanism of their antitumor effects is conceivably the altered metabolism of arachidonic acid and, subsequently, prostaglandins (PGs). Although COX-2, the inducible isoform, is regularly expressed at low levels in colonic mucosa, its activity increases dramatically following mutation of the APC (adenomatous polyposis coli) gene suggesting that beta-catenin/T-cell factor mediated Wnt-signaling activity may regulate COX-2 gene expression. In addition, hypoxic conditions and sodium butyrate exposure may also contribute to COX-2 gene transcription in human cancers. The development of selective COX-2 inhibitors has made it possible to further evaluate the role of COX-2 activity in colorectal carcinogenesis. To date, at least five mechanisms by which COX-2 contributes to tumorigenesis and the malignant phenotype of tumor cells have been identified, including: (1) inhibition of apoptosis; (2) increased angiogenesis; (3) increased invasiveness; (4) modulation of inflammation/immuno-suppression; and (5) conversion of procarcinogens to carcinogens. A clear positive correlation between COX-2 expression and inhibition of apoptosis has been established, associated with increased PGE2 levels resulting in modulation of pro- and anti-apoptotic factors (e.g., bcl-2, MAKs/ras, caspase-3, Par-4). In terms of angiogenesis and invasiveness, COX-2 activity was found to increase the expression of growth factors (e.g., VDEG, PDGF, bFGF) and matrix metalloproteinases (MMPs). Since COX-2 inhibitors have been demonstrated to interfere with tumorigenesis and apoptosis, COX-2 and its gene product may be attractive targets for therapeutic and chemoprotective strategies in colorectal cancer patients. This may lead to new perspectives that by controlling the cancer phenotype, rather than attempting to eradicate all affected cells, may provide significant benefits to the cancer patient.
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PMID:Cyclooxygenase-2: a novel target for cancer chemotherapy? 1146 77

1. In the present study, we describe the expression of the neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) as well as their receptors in PC-3 cells, a human prostate cancer cell line. In addition, we have investigated their role in apoptosis induced by serum starvation. 2. By RT-PCR and immunocytochemistry assays, we have demonstrated the production of VIP and PACAP in PC-3 cells. 3. We have demonstrated by RT-PCR and binding assays the expression of common PACAP/VIP (VPAC(1) and VPAC(2)) receptors, but not PACAP-specific (PAC(1)) receptors. The pharmacological profile of [(125)I]-VIP binding assays was as follows: VPAC(1) antagonist=VPAC(1) agonist>VIP>VPAC(2) agonist (IC(50)=1.2, 1.5, 2.3 and 30 nM, respectively). In addition, both receptor subtypes are functional since VIP, PACAP-27 or VPAC(1) and VPAC(2) agonists all increased the intracellular levels of cAMP. 4. The expression of both peptides and their receptors is similar in serum-cultured and serum-deprived PC-3 cells. The treatment of serum-deprived PC-3 cells with exogenous VIP or PACAP-27 increases cell number and viability in a dose-dependent manner, as demonstrated by cellular counting and MTT assays. The increased cell survival is exerted through the VPAC(1) receptor, since a VPAC(1), but not VPAC(2), receptor agonist, mimics the effects and a VPAC(1) receptor antagonist blocks it. Moreover, VIP and PACAP-27 inhibit genomic DNA fragmentation in PC-3 cells triggered by serum starvation, and increase the immunoreactivity of the antiapoptotic protein bcl-2. 5. Our results suggest that VIP and PACAP are autocrine/paracrine factors that protect PC-3 cells from apoptosis through VPAC1 receptors.
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PMID:VIP and PACAP are autocrine factors that protect the androgen-independent prostate cancer cell line PC-3 from apoptosis induced by serum withdrawal. 1283 80


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