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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor suppressor genes APC and MCC were identified recently, and their chromosomal location was ascribed to chromosome 5q21. Mutations in the APC gene give rise to familial adenomatous polyposis and occur in many perhaps even the majority, of sporadic colon cancers. Loss of heterozygosity has been described in other human tumors such as lung and esophageal cancers. Here we show loss of heterozygosity (LOH) in 87 patients with breast cancer for the APC and/or MCC loci using a polymerase chain reaction-LOH assay. LOH affected loci in APC exons 11 and 15 in 9 of 35 (25%) and 4 of 34 (11%) heterozygous patients, respectively. LOH at the MCC exon 10 locus occurred in 7 of 40 (17%) informative samples. These data suggest that allelic deletion of APC and/or MCC is probably involved in the pathogenesis and/or progression of a subset of breast cancers.
Cancer Epidemiol Biomarkers Prev 1994 Jun
PMID:Loss of heterozygosity affecting the APC and MCC genetic loci in patients with primary breast carcinomas. 806 82

We used Southern blot analysis and polymerase chain reaction-based techniques to examine deletions of tumour suppressor gene loci in 91 primary colorectal tumours. The tumour suppressor genes studied were MCC and APC on chromosome 5q, p53 on chromosome 17p, DCC on chromosome 18q, and the putative suppressor gene nm23-H1 on chromosome 17q. The most frequent allelic loss observed was in chromosome 17p with 76% (68/89) of informative tumours showing loss of heterozygosity at this locus, followed by 34% (19/55) for DCC, 31% (12/39) for MCC, 17% (9/53) for APC and 16% (3/19) for nm23. No significant differences in the frequency of these suppressor gene allelic losses were observed between Dukes B and C stage adenocarcinomas.
Eur J Cancer 1994
PMID:Loss of heterozygosity of tumour suppressor gene loci in human colorectal carcinoma. 808 Jun 84

It is known that immunoglobulins can be processed and that idiotypic peptides are presented on MHC class II molecules to T cells. It has also been demonstrated that T cells can recognize a complex of an Id-peptide/MHC molecule as a tumor-specific antigen on B lymphoma cells. However, plasmacytomas, an important type of B cell malignancies, most often lack class II molecules and are thus expected to be poor targets for Id-specific, CD4+ T cells. Nevertheless, we now demonstrate that cloned, MHC class II restricted T cells, specific for a lambda 2(315) idiotypic peptide, convey protection in vivo (Winn assay) against the class II molecule-negative MOPC315 (alpha, lambda 2(315)) plasmacytoma. T cells can also inhibit the growth of MOPC315 cells in vitro provided that MHC compatible (H-2d) splenocytes and extra lambda 2(315) are added. Based on these data we suggest that the myeloma protein secreted by MOPC315 cells attains such a high local concentration in vivo that it is processed and presented by neighboring host APC to the Id-specific T cells. Such activated T cells secrete lymphokines which may directly affect the growth of MOPC315 cells in the vicinity. Alternatively, lymphokines from activated T cells stimulate local host cells, like macrophages, to become tumoricidal.
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PMID:The role of idiotype-specific, CD4+ T cells in tumor resistance against major histocompatibility complex class II molecule negative plasmacytoma cells. 809 65

Genetic and environmental aspects play an important role in the development of colorectal cancer. However, the common molecular alteration in both hereditary and sporadic colon cancer is localized in the APC gene. the APC gene maps in the long arm of chromosome 5 and was discovered in patients with familial adenomatous polyposis (FAP). The search for the APC gene led to the identification of restriction fragment length polymorphisms (RFLPs) in FAP patients. Using these RFLPs in relatives of FAP patients it is possible to make the presymptomatic and prenatal diagnosis. The FAP syndrome is an interesting model of carcinogenesis in vivo. Thus the different stages involved in the FAP syndrome which include hyperproliferative epithelium, adenoma, adenocarcinoma and metastases, have allowed the analysis of molecular alterations in oncogenes and tumor suppressor genes. The APC gene alteration if not inherited, occurs as the earliest molecular alteration in the development of colorectal cancer whereas structural alterations of the genes myc, ras, p53, MCC and DCC are considered to be late events. All these investigations have lead to 1) a better understanding of the ethiology of cancer and 2) early diagnosis of colorectal cancer in both the hereditary and sporadic forms of the disease.
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PMID:[Molecular genetics of colorectal cancer and carcinogenesis]. 813 31

The detection in tumors of genomic regions with a high frequency of loss of heterozygosity has led to the localization and subsequent cloning of a number of tumour suppressor genes. To identify such regions involved in the development of squamous carcinoma of the head and neck we have analyzed 28 paired normal and tumor DNA samples. Using the polymerase chain reaction to amplify 50 simple sequence repeats or microsatellite markers we have studied all 22 q limbs and 17 of the p limbs in 21 patients. In informative cases we observed a high incidence of loss of heterozygosity at five specific chromosomal regions: 3p (44%); 5q (43%); 9q (35%); 11q (45%); and 17p (31%). In addition, further analysis of tumors showing loss of heterozygosity at 5q suggests that a gene at or near the APC locus is involved in squamous carcinoma of the head and neck.
Cancer Res 1994 Apr 01
PMID:An allelotype of squamous carcinoma of the head and neck using microsatellite markers. 813 68

The study of the genetic alterations of tumor suppressor genes and protooncogenes in solid tumors has greatly increased our understanding of cancer biology. These findings have extended epidemiologic associations of carcinogens with certain tumors. Further analysis of patterns of genetic changes may implicate carcinogenic substances in cases where epidemiology has not been able to do so. Identification of germline mutations in p53, APC, and NF1 has provided improved diagnosis and presymptomatic screening in cancer kindreds. The identification of additional alterations in tumor suppressor genes may further improve the ability to predict inherent cancer risk. Screening strategies based on detection of genetic abnormalities of preinvasive cancerous lesions, such as mutant ras in colonic polyps, may improve early diagnosis. Finally, strategies to replace lost tumor suppressor function may provide a future therapeutic modality.
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PMID:Genetic mechanisms of solid tumor oncogenesis. 814 Sep 69

Knowledge of the patterns of allelic loss has been useful in identifying the spectrum of the tumor suppressor genes involved in various tumor types. Such analyses in pancreatic carcinoma have been difficult due to the characteristic host desmoplastic reaction to the neoplasm. We have assembled the first allelotype of pancreatic adenocarcinoma, a survey for allelic loss among each chromosomal arm, using seven cryostat-dissected neoplasms. The fractional allelic loss in these seven neoplasms was 0.18, a value similar to that seen previously in colorectal carcinoma. Alleles of chromosome 18q (lost in five of six informative tumors) and of chromosome 17p (lost in four of five informative tumors) were commonly affected. Neither APC mutations (33 neoplasms), allelic shifts of dinucleotide repeats (26 neoplasms), nor immunohistochemical evidence of retinoblastoma protein underexpression (7 neoplasms) were found. Further evaluation of allelic loss in pancreatic cancer would benefit from improved methods for the analysis of lost genetic material which overcome the problems posed by the high admixture of nonneoplastic stromal and inflammatory cells in these tumors.
Cancer Res 1994 May 15
PMID:Allelotype of pancreatic adenocarcinoma. 816 8

Chemical carcinogenesis is a multistage process that includes initiation, promotion, and progression. Some carcinogenic PACs have been shown to activate proto-oncogenes and deactivate tumor-suppression genes in the carcinogenic process. The function of DNA repair processes appears to be changed in some cases by PACs. Many PACs are well known for their carcinogenic activity, but for this activity to be exerted, metabolic activation by microsomal enzymes must occur. The enzyme system responsible for PAC activation is the mixed-function oxidase system and, in particular, cytochrome P-450. In the case of PAHs, oxidation predominantly produces reactive diol-epoxides that can then be converted to carbonium ions as the reactive electrophiles that can then covalently bind to DNA. Regions of high activity exist in PAHs, namely, the "bay," "K," and "L" regions which are associated with pi electron distribution. The diol-epoxides can exist in either syn or anti forms, each of which has two enantiomers producing four stereoisomers in all. Energy considerations favor the formation of the anti form. Nitrogen-containing PACs can be metabolically activated in a manner similar to that for PAHs, or the nitrogen atom can be oxidized to form hydroxylamines. These reactive electrophiles can then form covalently bound DNA adducts. The monitoring of DNA adducts has been used in risk assessment for human exposure to PACs. This form of biomonitoring has advantages over the monitoring of external exposure or body levels of the chemicals in question. In the case of PACs, binding to DNA is an important step in the multistage carcinogenic process. The estimation of DNA adducts has been used in the monitoring of humans exposed to PAHs in a wide range of industrial situations. Recent research has shown a dose-response relationship between PAH adduct levels and human cancer, thus developing molecular epidemiology as a relevant science for the field of risk assessment. Techniques have been developed for the determination of DNA adducts and these include immunochemical, fluorescence spectroscopic, GC-MS, and 32P-postlabeling methods. The 32P-postlabeling assay is by far the most sensitive, with limits of detection being of the order of one adduct in 10(10) normal nucleotides. The use of HPLC for separation of adducted nucleotides in this postlabeling assay is becoming more common and gives better resolution of adducts than does the TLC technique used in the traditional assay. The detection of adducts on hemoglobin and other proteins has been used as a surrogate for DNA adduct estimation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Prediction and monitoring of the carcinogenicity of polycyclic aromatic compounds (PACs). 817 Dec 14

The association of cisplatin plus cyclophosphamide (PC) is considered to be the standard medical treatment for advanced ovarian carcinoma, while the role of doxorubicin in combination with cisplatin and cyclophosphamide (PAC regimen) is still controversial. Recently, four randomized clinical trials evaluating PC versus PAC regimen have been published. None of these studies showed a convincing advantage for the addition of doxorubicin to PC. By pooling the data from the 1200 or so patients included in these four studies and analyzing them with the statistical technique of meta-analysis, a statistical benefit for PAC over PC is demonstrated in terms of pathologic complete response rate (30 vs 23%, P = 0.01) and 6-year survival rate (27 vs 21%, P = 0.01).
Bull Cancer 1993 Feb
PMID:Role of anthracyclines in first line combination chemotherapy of ovarian carcinoma. 817 67

The development of colorectal polyps and cancer in patients with familial adenomatous polyposis (FAP) is directly linked to inactivation of the APC gene. Other, epigenetic, mechanisms may be involved in tumorigenesis and a previous study suggested that an intrinsic difference in the biliary bile acid profile of untreated patients with FAP persisted after colectomy. Gas chromatography and gas chromatography-mass spectrometry were used to examine the biliary bile acid profiles of four groups of patients with normal gallbladders: 20 patients with an intact colon comprising 12 with FAP and eight controls; and 26 patients after colectomy comprising 12 with FAP and 14 controls. Comparison of ten different bile acids from both amidate fractions (glycine and taurine) revealed a small increase in the molar percentage of a minor bile acid (12-oxolithocholic acid) in patients with FAP and an intact colon compared with the matching control group. Colectomy was associated with a dramatic reduction in levels of secondary bile acids but with little difference between patients with FAP and controls.
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PMID:Biliary bile acid profiles in patients with familial adenomatous polyposis before and after colectomy. 817 25


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