Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To assess changes in aldolase isozyme patterns (A, B, and C) in renal cell carcinoma (RCC) tissues and to evaluate whether serum aldolase A might be a useful marker for RCC, quantitative analysis by enzyme immunoassay and immunohistochemical localization were performed. Concentrations of aldolase A in RCC (7300 +/- 6300 ng./mg. protein n = 26) were significantly higher than those of normal cortex (720 +/- 410 ng./mg. protein, n = 14, p less than 0.01); concentrations of aldolase C in RCC (48.0 +/- 8.0 ng./mg. protein) were also significantly higher than those of normal cortex (8.7 +/- 4.7 ng./mg. protein, p less than 0.01). On the other hand, concentrations of aldolase B in normal cortex were 18,100 +/- 10,100 ng./mg. protein (n = 14), whereas the values in RCC were only 130 +/- 270 ng./mg. protein, a significant lowering (p less than 0.01). Immunohistochemically, aldolases A and C were found localized in all RCC tissues (n = 10); aldolase B was faintly stained in only a few tumor cells of two cases (20%). Levels of serum aldolase A were elevated (greater than 300 ng./ml.) in 30 (75%) of 40 patients with RCC as compared to three (6.3%) of 48 individuals with urogenital benign diseases and in seven (21%) of 34 cases with non-RCC urogenital malignancies. Since it is generally accepted that RCC are derived from renal proximal tubules, these findings indicate that aldolase B, the predominant isozyme in the normal case, changes into aldolases A and C during carcinogenesis and that serum aldolase A could be a new useful biomarker for RCC.
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PMID:An immunochemical and immunohistochemical study of aldolase isozymes in renal cell carcinoma. 185 54

Recently it has been known that the active form of vitamin D, 1 alpha, 25-dihydroxyvitamin D (1 alpha, 25-(OH)2D), plays some immunological roles in controlling cell differentiation and carcinogenesis. Moreover, 1 alpha, 25-(OH)2D is said to have some effects in the changes of several numbers of oncogenes. In this study, the serum concentrations of 1 alpha, 25(OH)2D and 25-hydroxyvitamin D (25-(OH)2D) were measured in 30 patients with renal cell carcinoma. The two vitamin D metabolites were separated and purified using high performance liquid chromatography, and each fraction was subjected to competitive protein binding assay using vitamin D deficient rat serum for 25-(OH)2D and chick embryo intestinal receptors for 1 alpha, 25-(OH)2D as the binder. The average concentration of serum 1 alpha, 25-(OH)2D was 28.9 +/- 5.2 pg/ml for controls whereas the average in patients with renal cell carcinoma was 19.7 +/- 5.9 pg/ml. The concentration of 1 alpha, 25-(OH)2D was significantly lower in the patients with renal cell carcinoma compared to in the controls (p less than 0.01). The average concentrations of serum 25-(OH)2D had no significant differences between the two groups. Comparison between the stage I + II and stage III + IV, T1 + T2 and T3 + T4, rapid type and slow type groups showed that the average serum 1 alpha, 25-(OH)2D concentrations was significantly lower in the stage III + IV, T3 + T4, and rapid type groups compared to the other groups (p less than 0.01, p less than 0.05, p less than 0.01). And besides there were no significant correlations between the concentration of serum 1 alpha, 25-(OH)2D and creatinine clearance in patients with renal cell carcinoma. Taken together, it is suggested that the serum concentration of 1 alpha, 25-(OH)2D is in some way correlated with the progression of renal cell carcinoma.
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PMID:[A study of the metabolism of vitamin D in patients with renal cell carcinoma--with special reference to serum concentration of 1 alpha, 25-(OH)2D and its clinical significance]. 188 Oct 8

Using the polymerase chain reaction (PCR), a human kidney glutathione S-transferase (GST) alpha cDNA clone (GST alpha 12 K) was synthesized; it is identical to a known liver GST alpha cDNA clone except for one base change (G----A), indicating that an alpha class gene expressed in human kidney is similar to one expressed in human liver. Comparisons were made in the expression of GST alpha and GST pi between renal cell carcinoma and adjacent non-neoplastic tissue. Messenger RNA expression in 30 cases was determined by Northern blotting, and GST protein from nine of these cases was analyzed by HPLC. The GST alpha gene products were expressed at near-zero levels. The GST pi gene product was the predominant GST in tumors, but was decreased in absolute amount compared with control tissue, the tumor/control ratios for the GST pi gene obtained by Northern blots and HPLC analysis being 0.50 +/- 0.07 and 0.36 +/- 0.07 respectively. The resulting pattern in renal cell carcinoma therefore shows a predominance of GST pi. Since it is assumed that renal cell carcinoma derives from the proximal tubular epithelial cells which are high in GST alpha, this implies a dedifferentation in the GST expression pattern.
Carcinogenesis 1990 Dec
PMID:Decreased expression of the glutathione S-transferases alpha and pi genes in human renal cell carcinoma. 226 70

Thyroid hormone participates in numerous cellular functions besides thermogenesis and metabolism. Several studies, including the recent identification of the product of an oncogene, c-erb-A, as a thyroid-hormone receptor, have shown possible involvement of thyroid hormone in the process of carcinogenesis. A recent anecdotal observation of an unusually high incidence of thyroid dysfunction in women with renal cell carcinoma led to a retrospective review of the incidence and distribution of thyroid disorders in women with renal cell carcinoma compared with a control group of women with transitional cell carcinoma of the renal pelvis, ureter, bladder, or urethra. Women with renal cell carcinoma had a statistically significantly higher percentage of hypothyroidism, thyroid disease in general, and the use of thyroid-hormone supplements as compared with the control group (P = 0.033, P = 0.005, P = 0.041, respectively). The nature of the relationship, however, could not be determined. These findings add a new dimension to renal cell carcinoma, and prospective studies are encouraged to define the contribution of thyroid hormone to renal cell carcinogenesis.
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PMID:Relationship of thyroid disease to renal cell carcinoma. An epidemiologic study. 235 76

The role of ras oncogenes in the pathogenesis of renal cell carcinoma is unclear. We have previously shown that insertion of a mutated ras oncogene into cultured human proximal tubular cells, the normal counterpart of renal cell carcinomas, initiates a series of transformation events which results in cells possessing a renal cancer phenotype. These data suggested a role for mutated ras genes in the initiation and maintenance of this disease. Therefore, to assess the involvement of ras genes in renal carcinogenesis, 51 primary and metastatic renal carcinomas, including three oncocytomas, were analyzed for point mutations in codons 12, 13 and 61 of the Ha-ras, Ki-ras and N-ras proto-oncogenes using polymerase-catalyzed chain reaction methodology. A mutated Ha-ras gene was found in one renal cancer metastatic to lung for an overall incidence of 2%. These data indicate that ras oncogenes, activated by point mutations, do not play a major role in the initiation, maintenance or metastases of renal carcinomas.
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PMID:Infrequent ras oncogene point mutations in renal cell carcinoma. 240 98

Glutathione S-transferase (GST) in man comprise at least four gene families. Three of these families give rise to cytosolic isoenzymes (alpha, mu and pi classes), whilst the remainder is membrane bound and has been called microsomal GST. These enzymes are implicated in tumourogenesis and both pi class GST and alpha class GST have been described in four cases of human renal cell carcinoma. Using specific polyclonal rabbit antisera we have demonstrated by immunohistochemistry that all 12 renal carcinomas studied contained GST pi. Most tumours also contained GST alpha, GST mu and microsomal GST isoenzymes but their distribution was heterogeneous and sometimes very focal. This heterogeneity of GST isoenzyme distribution within tumours has not been well documented previously, but is relevant to our understanding of the functions of GST, and to the interpretation of biochemical quantification experiments using tissue extracts.
Carcinogenesis 1989 Jul
PMID:Glutathione S-transferase isoenzymes in human renal carcinoma demonstrated by immunohistochemistry. 266 Oct 44

Catechol-O-methyltransferase (COMT) [EC 2.1.1.6] is a ubiquitous cytosolic enzyme which has a pertinent role in the inactivation of both natural and synthetic catechol estrogens in mammalian tissues. We have compared the COMT activity in mouse, hamster and rat kidney, liver and red blood cells and examined the kinetic characteristics of this enzyme in the latter two species using various catechol estrogens as substrates. Results presented here indicate that the ratios of COMT activity in the kidney versus the liver of the rat and mouse are nearly identical, 0.48-0.52, whereas there is a 29-fold ratio between the level of COMT activity in these two tissues in the hamster. In red blood cells, the level of COMT activity is 4- and 12-fold lower in the hamster compared to mouse and rat, respectively. When the kinetic characteristics of this enzyme were assessed in the hamster and rat kidney and liver, except for 2-hydroxymoxestrol which had an apparent Km value of 15-48 microM, the other catechol estrogen substrates exhibited Km values ranging from 1-10 microM. Generally, the Vmax values were markedly higher in the rat kidney and liver than those observed in corresponding hamster tissues. The significantly lower COMT activity in the hamster liver and red blood cells suggests that under chronic estrogen treatment at high doses, the concentration of catechol estrogens in these tissues may exceed the capacity of COMT to effectively catalyse their O-methylation into inactive metabolites. The resulting accumulation of catechol estrogens may contribute to the estrogen carcinogenicity observed in the hamster liver and kidney. Additionally, when 2-hydroxyestrone was used as a substrate, the estrogen-induced renal carcinoma exhibited only 8.6% of the COMT activity found in the normal kidney.
Carcinogenesis 1989 Jan
PMID:Variations in catechol O-methyltransferase activity in rodent tissues: possible role in estrogen carcinogenicity. 291 May 32

Estradiol and other estrogens induce renal carcinoma in male Syrian hamsters. The mechanism of carcinogenesis still remains unclear. Activation of estrogens to catechol metabolites has in the past been postulated to play a role in estrogen-induced carcinogenesis. Therefore, the carcinogenic activity of catechol estrogens was investigated. After 175 days of treatment, 4-hydroxyestradiol was found to be as carcinogenic as estradiol in male Syrian hamsters (4/5 and 4/5 animals with kidney tumors, respectively). Animals treated with 2-hydroxyestradiol (0/5) or 2-methoxyestradiol (0/6) did not develop renal carcinoma. The catechol estrogens failed to be mutagenic in the Ames test (reversions of his- S. typhimurium to histidine prototrophy in the TA 100 strain). The lack of carcinogenic activity of 2-hydroxyestradiol was not due to a failure to stimulate estrogen-dependent tumor growth. Growth of H-301 cells, an estrogen-dependent hamster kidney tumor cell line, was supported in vivo by estrogens in the following order: estradiol greater than 4-hydroxyestradiol greater than 2-hydroxyestradiol. Stimulation of tumor growth by 2-methoxyestradiol was not detected. It was concluded that the carcinogenic activity of 4-hydroxyestradiol was consistent with a role of catechol metabolites in estrogen-induced carcinogenesis. However, the intrinsic carcinogenic or hormonal activity of 2-hydroxyestradiol probably can not be assessed accurately in vivo because of its rapid methylation and metabolic clearance.
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PMID:Carcinogenicity of catechol estrogens in Syrian hamsters. 300 86

In order to discriminate non-specific toxicity from the early precursor lesions of neoplasia, emphasis in these studies has been on the use of models requiring only a single administration of chemical. Our interests have focussed on three neoplastic entities in the kidney, renal mesenchymal neoplasia, renal cell carcinoma, and nephroblastoma. Dimethylnitrosamine administered as a single intraperitoneal injection to immature female Wistar rats, pre-conditioned for several days with a no-protein/sugar-only diet, has been used for investigating the complex morphological nature of renal mesenchymal tumors, their pathogenesis and the development of cell culture correlates. The near 100% tumor incidence and its facility for cell culture manipulation makes this a particularly potent model for studying chemical carcinogenesis and the evolution of cell transformation. Discovery that the rat kidney response to DMN was biphasic with respect to the time of treatment led to the subsequent development of a high incidence system for inducing renal adenocarcinoma, using older rats. Renal cell carcinomas could also be induced in mice by a single intravenous injection of streptozotocin. The tumor frequency in female CBA/H/T6J mice was almost 100%, providing a new model for the investigation of renal carcinogenesis in this species. Nephroblastoma has been a poorly comprehended neoplasm in both lower animals and man because of the lack of a high incidence model in conventional laboratory mammals. Recently, we have exploited an increased spontaneous predisposition of the Nb rat to nephroblastoma using a single intraperitoneal dose of N-ethylnitrosourea in pregnant females on day 18 of gestation, producing a frequency of 50% for this tumor type. More potent however, was a system which utilized the partially inbred IIIVO/J strain of rabbit using the same carcinogen and transplacental route of administration. The resultant incidence of nephroblastomas in the progeny was in excess of 90%, and like their counterparts in man, the neoplasms developed rapidly and had a potential for distant metastasis. Each one of these animal models is suitable for the sequential tracing of tumor pathogenesis, and in depth analysis of the biochemical and molecular mechanisms involved in the initiation and formation of different types of renal cancer.
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PMID:Experimental models for the sequential analysis of chemically-induced renal carcinogenesis. 301 58

In estrogen-induced cancer, catechol formation from administered steroids has been postulated to be a necessary event for estrogen activation and subsequent damage to cellular macromolecules. In the present study, this hypothesis has been tested using two homologous series of structurally related estrogens: estradiol, 11 beta-methylestradiol, 11 beta-ethylestradiol, 11 beta-methyl-17 alpha-ethinylestradiol, 11 beta-ethyl-17 alpha-ethinylestradiol, 11 beta-methoxy-17 alpha-ethinylestradiol, and 17 alpha-ethinylestradiol. In the Syrian hamster renal carcinoma model, only 11 beta-methylestradiol and 17 alpha-ethinylestradiol were weak carcinogens (2 of 20 and 2 of 24 hamsters with tumors, respectively). The other estrogens tested induced renal carcinoma within 6 to 9 months with an incidence in the 80-100% range. The tumor incidence in vivo did not correlate with the rates of catechol formation by hamster kidney microsomes in vitro. Compared to estradiol (relative rate, 100), catechol formation by the substituted estrogens was significantly lower, ranging from 48 (11 beta-methylestradiol) to 2 (11 beta-methoxy-17 alpha-ethinylestradiol). Kidney DNA of hamsters treated with the four 17 alpha-ethinyl estrogens, when analyzed by 32P postlabeling assay, contained the same set of covalently modified nucleotides the formation of which had previously been found to precede estrogen-induced renal carcinogenesis in vivo. In contrast, relative rates of catechol estrogen formation by BALB/c 3T3 microsomes correlated with induction of morphological transformation of BALB/c 3T3 cells and decreased in the following order: 11 beta-methylestradiol greater than 17 alpha-ethinylestradiol greater than or equal to estradiol greater than 11 beta-ethylestradiol greater than 11 beta-methoxy-17 alpha-ethinylestradiol. The hormonal potencies of several estrogen derivatives studied by various assays did not correlate with in vivo carcinogenic or in vitro cell-transforming activities. It is concluded from these experiments that in cell culture catechol formation and morphological transformation are directly related. In vivo, aromatic hydroxylation of administered estrogens did not correlate with the incidence of estrogen-induced renal carcinoma in Syrian hamsters.
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PMID:Correlation of aromatic hydroxylation of 11 beta-substituted estrogens with morphological transformation in vitro but not with in vivo tumor induction by these hormones. 303 10


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