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

A nation-wide clinical trial on a new antineoplastic drug, carboplatin(CP) supplied by Qilu Pharmaceutical Company, was carried out during the period of January to September 1989. Two hundred and forty-three patients with various malignant tumors were treated by CP as a single agent, 167-436 mg/m2 by intravenous infusion, repeated every 4 weeks, and 2-4 cycles as a course. The response rate was 75% (6/8) in testicular cancer, 56% (9/16) in ovarian cancer, 63% (15/24) in head and neck cancer, 37% (15/41) in small cell lung cancer and 60% (25/42) in non-Hodgkin's lymphomas. Randomized study of combination chemotherapy containing CP or cisplatin (DDP) was also conducted. The results showed that in small cell lung cancer, 73% (30/41) of the the patients responded to CE (CP + VP - 16) and 67% (24/36) responded to PE (DDP + VP - 16) and in ovarian cancer, the response rate was 60% (6/10) to CAC (CP + adriamycin + cyclophosphamide) and 36% (4/11) to PAC (DDP + adriamycin + cyclophosphamide) regimen. In addition, gastrointestinal reaction and renal toxicity were less severe in regimens containing CP than in regimens containing DDP. However, CP had more marked myelosuppressive effect.
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PMID:[Clinical results of carboplatin in the treatment of malignant tumors. Clinical Cooperative Group of Carboplatin]. 217 94

Little is known of the molecular changes that occur in germ cell tumors (GCT) of the testis. We studied three GCT cell lines and 44 tumors for loss of heterozygosity (LOH) of the tumor suppressor genes APC, MCC, DCC, RB, TP53, and WT-1. We observed that LOH occurred in 55% (21 of 38) of informative cases at DCC, in 28% (10 of 36) of informative cases at APC, in 23% (6 of 26) at MCC, in 30% (13 of 43) at RB, and in 27% (6 of 22) at WT-1. The LOH level in these tumors using anonymous primers mapping to the short and long arms of chromosome 19, which is cytogenetically normal in GCT, revealed LOH of 11 and 5%, respectively. We also observed a LOH of 22% in the TP53 gene, despite the fact that mutations in TP53 do not occur in testis cancer. Since a high frequency of LOH at DCC (18q21.3) occurs equally at all histological subsets in GCT, we conclude that the loss of the function of this gene is an early event in testicular GCTs. However, the observed LOH levels at APC/MCC (5q21), RB (13q14), and WT-1 (11p13) could represent a functional loss of the corresponding tumor suppressor gene in some GCTs or reflect the loss of sequences in the same general chromosome region but involving a different tumor suppressor locus. Therefore, detailed mapping of these chromosomes is required to define the precise locations of maximal LOH in testis cancer.
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PMID:Loss of heterozygosity of tumor suppressor genes in testis cancer. 779 15

It was previously demonstrated that miR-199a was downregulated in testicular germ cell tumor (TGCT), probably due to hypermethylation of its promoter. Further study found that re-expression of miR-199a in testicular cancer cells (NT2) led to suppression of cell growth, cancer migration, invasion and metastasis. More detailed analyses showed that these properties of miR-199a could be assigned to miR-199a-5p, one of its two derivatives. The biological role of the other derivative, miR-199a-3p in TGCT, remains largely uncharacterized. In this report, we identified DNA (cytosine-5)-methyltransferase 3A (DNMT3A), the de novo methyltransferase, as a direct target of miR-199a-3p using a 3'-UTR reporter assay. Transient expression of miR-199a-3p in NT2 cells led to decrease, while knocking down of miR-199a-3p in a normal human testicular cell line (HT) led to elevation, of DNMT3A2 (DNMT3A gene isoform 2) mRNA and protein levels. In clinical samples, DNMT3A2 was significantly overexpressed in malignant testicular tumor, and the expression of DNMT3A2 was inversely correlated with the expression of miR-199a-3p. However, DNMT3A did not affect miR-199a expression in NT2 cells. Further characterization of miR-199a-3p revealed that it negatively regulated DNA methylation, partly through targeting DNMT3A. Overexpression of miR-199a-3p restored the expression of APC and MGMT tumor-suppressor genes in NT2 cells by affecting DNA methylation of their promoter regions. Our studies demonstrated the deregulation of miR-199a-3p expression in TGCT may provide novel mechanistic insights into TGCT carcinogenesis and suggested a potentially therapeutic use of synthetic miR-199a-3p oligonucleotides as effective hypomethylating compounds in the treatment of TGCT.
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PMID:microRNA-199a-3p, DNMT3A, and aberrant DNA methylation in testicular cancer. 2395 88