Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Constitutional loss or inactivation of one copy of a tumor-suppressor gene, as exemplified by hereditary retinoblastoma, increases the propensity for malignancies by reducing the number of events necessary for the complete loss of the negative regulatory function. We developed a selectable mutation assay employing a human lymphoblastoid cell line (LCL) derived from a heterozygous carrier of 2,8-dihydroxyadenine urolithiasis, adenine phosphoribosyltransferase (APRT) deficiency, for dissecting the second step in loss-of-function mutations and for determining the potential of physical and chemical agents for producing such mutations. The mode of mutational events arising in the wild-type allele of the functionally heterozygous APRT gene resembled that reported for tumor-suppressor genes in malignancies in that mitotic non-disjunctions or recombinations as well as deletions prevailed. Ultraviolet light (UV) was much less efficient in inducing these types of mutations than ionizing radiation. A group of autosomal recessive cancer-prone diseases, including xeroderma pigmentosum (XP), has been characterized as being more susceptible to genomic insults, owing to some defects in DNA processing, such as replication, repair, or recombination. This increased genomic instability may accelerate the gain-of-function mutation at a proto-oncogene and/or the loss-of-function mutation at a tumor-suppressor gene. XP complementation group A (XP-A) LCLs were extremely sensitive to UV-mutagenesis at the hypoxanthine phosphoribosyltransferase (HPRT) locus even at equicytotoxic doses. Some unique mechanism may operate in UV-mutagenesis in XP-A. We have succeeded for the first time in rendering XP-A cells tumorigenic in athymic mice by applying multiple exposures to UV and subsequent treatment with TPA.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Molecular bases for hereditary cancer-prone diseases. 129 55

Calcium phosphate, fluoroapatine mineral, Ca5(PO4)3F, characterized by a strong reflex in interplanar distance d = 2.789 A, were identified in the tissue of retinoblastoma by x-ray destructive analysis. The strong reflex intensity and the respective fluoroapatite level in the tumor are the higher, the more malignant the tumor is. The malignancy degree is determined by histologic analysis of the tumor cellular composition after enucleation.
 ...
PMID:[Pathological mineralization in retinoblastoma]. 129 91

One-hundred pediatric patients with uni- and bilateral retinoblastoma (140 tumors on the whole) received a combination of radio- and chemotherapy. Radiation was delivered by gamma-ray units and an electron accelerator. The single and total focal doses used were 1.5-2.0 Gy and 40-55 Gy, respectively, depending on tumor stage. Simultaneously, chemotherapy with vincristine, cyclophosphamide and adriamycin were given intravenously in standard doses. As a result, 85 out of 95 (89.5%) children including 43 cases of bilateral tumor are alive. Partial response or no change were registered in 72 tumors (51.4%). Progression was observed in 28 tumors (20%) at the average of 6-8 months following the start of treatment. Forty tumors (28.6%) responded completely, with remissions lasting for a follow-up period of 2-6 years. Not a single case of organ-sparing surgery developed distant metastases. To summarize, a combined treatment modality for retinoblastoma according to TNM stage was developed and indications for organ-sparing surgery outlined. The standard treatment modality for bilateral retinoblastoma was revised.
 ...
PMID:[The possibilities for organ-preserving treatment in retinoblastoma in children]. 130 Aug 24

Multiple genome alterations can be seen within a tumor and continue to accumulate throughout development of the growth. Chromosome deletions occurring in tumors are generating much interest. To date, the best known model is retinoblastoma whose study gave rise to the concepts of anti-oncogene or tumor suppressor gene. Studies of genetic anomalies in colorectal tumors have led to an elegant model of colonic carcinogenesis in which multiple steps, each with its corresponding genetic anomaly, successively accumulate, with deletion of the p53 gene occurring as a late event. Successive anomalies of the p53 gene (mutations, deletions) occur during passage from a low-grade astrocytoma to a higher-grade astrocytoma. Studies of familial forms of breast cancer and of breast and ovarian cancer have also provided insight into the biology of these tumors, with the identification of a predisposing chromosomal area whose location is 17 q-12-21. These approaches open up possibilities for screening techniques and use of preventive treatments in highly selected patients. However they raise many ethical problems. There is a need for developing a charter for these family studies in the near future.
 ...
PMID:[Genetics and cancers]. 130 91

We are now beginning to understand the development of bladder cancer at the molecular level. Tumor evolution involves the interaction of both oncogenes and tumor suppressor genes. One of the key tumor suppressor genes in this process is the retinoblastoma (RB) gene. Much has been learned recently about the role of this gene in the tumor progression and prognosis of bladder cancer, although several questions are still unanswered. The progress made on this subject in our laboratory as well as others will be the focus of this report.
 ...
PMID:Altered RB expression is a prognostic clinical marker involved in human bladder tumorigenesis. 130 91

Retinoblastoma is the most common intraocular malignancy of childhood. Trilateral retinoblastoma is a syndrome characterized by bilateral ocular retinoblastoma in conjunction with an intracranial neuroblastic neoplasm in the pineal body, or in supraseller or parasellar location. We report the case of a three year old girl with trilateral retinoblastoma and review the literature on this subject.
 ...
PMID:Trilateral retinoblastoma. 130 6

The retinoblastoma tumor suppressor gene product (pRb) is a nuclear protein subject to cell cycle-regulated hyperphosphorylation. I constructed a recombinant vaccinia virus vector that expresses both the underphosphorylated and hyperphosphorylated forms of pRb and purified the recombinant protein by using immunoaffinity chromatography directed toward a synthetic carboxy-terminal epitope. To investigate the hypothesis that hyperphosphorylation of pRb is a means of controlling its growth-regulating activity, I tested purified pRb for the ability to be reincorporated into pRb-deficient nuclei in vitro. The underphosphorylated form of pRb efficiently reassociated with nuclei, but the hyperphosphorylated form remained soluble in this assay. Nuclear binding of pRb was enhanced by phosphatase treatment and reduced by phosphorylation of pRb effected by using a preparation of the cell cycle-regulatory kinase p34cdc2. Mutant-encoded proteins with altered E1A-binding domains failed to bind to nuclei. Pretreatment of target nuclei with nucleases and high-salt extraction did not alter the specificity of binding for underphosphorylated pRb. These observations demonstrate that hyperphosphorylation of pRb can regulate its interaction with nuclei, supporting the hypothesis that hyperphosphorylation controls the growth-regulatory activities of pRb. Further, at least one target of pRb binding appears to be an integral component of the nuclear envelope.
 ...
PMID:Nuclear binding of purified retinoblastoma gene product is determined by cell cycle-regulated phosphorylation. 131 Jan 46

Stable interactions between simian virus 40 large T antigen and host proteins are believed to play a major role in the ability of the viral protein to transform cells in culture and induce tumors in vivo. Two of these host proteins, the retinoblastoma susceptibility protein (pRB) and p53, are products of tumor suppressor genes, suggesting that T antigen exerts at least a portion of its transforming activity by complexing with and inactivating the function of these proteins. While analyzing T antigen-host protein complexes in mouse cells, we noted a protein of 185 kDa (p185) which specifically coimmunoprecipitates with T antigen. Coimmunoprecipitation results from the formation of stable complexes between T antigen and p185. Complex formation is independent of the interactions of T antigen with pRB, p120, and p53. Furthermore, analysis of T-antigen mutants suggests that T antigen-p185 complex formation may be important in transformation by simian virus 40.
 ...
PMID:Simian virus 40 large T antigen stably complexes with a 185-kilodalton host protein. 131 Jul 76

The E7 gene of human papillomavirus type 16 encodes a multifunctional nuclear phosphoprotein that is functionally and structurally similar to the adenovirus (Ad) E1A proteins and the T antigens of other papovaviruses. E7 can cooperate with an activated ras oncogene to transform primary rodent cells, trans activate the Ad E2 promoter, and abrogate transforming growth factor beta-mediated repression of c-myc. Recent studies suggest that these functions may in part be a consequence of the ability of E7 to associate with the product of the retinoblastoma tumor suppressor gene (pRB). In this study, a series of site-specific mutations of the human papillomavirus type 16 E7 gene product were constructed and assessed for their effects on intracellular protein stability, ras cooperativity, transcriptional trans activation, pRB association, and phosphorylation. The results of these studies indicate that the transforming and trans-activating domains extensively overlap within a region of the protein analogous to conserved region 2 of Ad E1A, suggesting that pRB binding is necessary for both activities. Deletion of sequences in conserved region 1 abrogates cellular transformation but has only a marginal effect on trans activation. These data suggest that E7 trans activation and cellular transformation are interrelated but separable functions.
 ...
PMID:Structure-function analysis of the human papillomavirus type 16 E7 oncoprotein. 131 37

The development of Wilms' tumor, a pediatric kidney cancer, has been linked to the inactivation of a tumor suppressor gene both by epidemiologic studies and by genetic analyses. Like retinoblastoma, Wilms' tumors can occur bilaterally in individuals with apparent genetic susceptibility to this disease. This led Knudson and Strong to propose in 1972 that two genetic events were rate limiting in tumor development and that predisposed individuals had already inherited one mutation in the germline. The observation of karyotype abnormalities in predisposed children and studies of the molecular genetics of Wilms' tumor specimens enabled the identification of chromosome band 11p13 as one genetic locus inactivated in Wilms' tumor. The recent isolation of the WT1 gene, which is the specific target within that locus, offers new insight into the etiology of Wilms' tumor. This gene has properties distinct from those of other known tumor suppressor genes. WT1 encodes a zinc finger transcription factor that is alternatively spliced and has high sequence homology to the early growth response genes (EGR). Unlike the retinoblastoma (RB1) and p53 genes that are expressed ubiquitously, WT1 is expressed in specific cells of the kidney and only during a short period in development. Thus, disruption of a gene that is active during a critical period in the development of a specific organ can lead to neoplastic growth in that organ. Future studies are aimed at exploring the link between the role of the WT1 gene in normal development and in tumorigenesis of the kidney.
 ...
PMID:WT1: a novel tumor suppressor gene inactivated in Wilms' tumor. 131 85


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>