Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The localization of membrane-bound gamma-glutamyltransferase with monoclonal antibody (mAb) 138H11 proved to be of value for differential diagnosis of renal cancer, since it correlated with the histogenetic profile of human epithelial renal tumors. Immunoreactive gamma-glutamyltransferase was located in the proximal tubule in all normal human kidneys (15/15) examined thus far by both ultrastructural and immunohistochemical techniques. From 68 epithelial renal cancers tested 31/31 clear-cell carcinomas and 15/16 chromophilic carcinomas expressed the target epitope of mAb 138H11. In contrast, 0/11 oncytomas, 0/9 chromophobic carcinomas, and 0/1 Duct-Bellini carcinoma were immunoreactive. These results support a model of histogenesis and classification of epithelial renal tumours, according to which clear-cell and chromophilic renal carcinomas originate from transformed proximal tubule cells, whereas oncocytomas, chromophilic and Duct-Bellini carcinomas originate from cells of the collecting duct.
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PMID:Differential diagnosis of histogenetically distinct human epithelial renal tumours with a monoclonal antibody against gamma-glutamyltransferase. 167 84

The chromophobe renal cell carcinoma is a distinct type of renal cancer presumably derived from the intercalated cell of the collecting duct system and exhibiting a better prognosis than other types of renal cell carcinoma. Chromophobe carcinomas can be separated from other types of renal cell carcinoma by their characteristic cytomorphology, ultrastructural appearance, cytoskeletal architecture, and cytogenetic aberrations. As no permanent cell line of the chromophobe tumor type has previously been described, we are the first to report on the successful establishment and characterization of two divergent permanent cell lines, ie, chrompho-A and chrompho-B, derived from the same chromophobe renal cell carcinoma. With immunocytochemistry, two-dimensional gel electrophoresis, and Western blot, chrompho-A and chrompho-B exclusively exhibited cytokeratins (Nos. 7, 8, 18, and 19) but not vimentin. Ultrastructural studies revealed numerous cytoplasmic microvesicles as well as coated vesicles that are known to be characteristic features of the intercalated cell. Chrompho-B cells exhibited a shorter mean population doubling time (tD = 43 hours) than chrompho-A cells (tD = 51 hours). Both cell lines failed to produce tumors in nude mice with the subrenal capsule assay. Cytogenetic analyses revealed hyperdiploid chromosome numbers in both cell lines with telomeric associations as well as numeric aberrations known from chromophobe renal cell carcinomas in vivo.
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PMID:Establishment and characterization of two divergent cell lines derived from a human chromophobe renal cell carcinoma. 771 62

Germline mutations of the fumarate hydratase (FH, fumarase) gene are found in the recessive FH deficiency syndrome and in dominantly inherited susceptibility to multiple cutaneous and uterine leiomyomatosis (MCUL). We have previously reported a number of germline FH mutations from MCUL patients. In this study, we report additional FH mutations in MCUL and FH deficiency patients. Mutations can readily be found in about 75% of MCUL cases and most cases of FH deficiency. Some of the more common FH mutations are probably derived from founding individuals. Protein-truncating FH mutations are functionally null alleles. Disease-associated missense FH changes map to highly conserved residues, mostly in or around the enzyme's active site or activation site; we predict that these mutations severely compromise enzyme function. The mutation spectra in FH deficiency and MCUL are similar, although in the latter mutations tend to occur earlier in the gene and, perhaps, are more likely to result in a truncated or absent protein. We have found that not all mutation-carrier parents of FH deficiency children have a strong predisposition to leiomyomata. We have confirmed that renal carcinoma is sometimes part of MCUL, as part of the variant hereditary leiomyomatosis and renal cancer (HLRCC) syndrome, and have shown that these cancers may have either type II papillary or collecting duct morphology. We have found no association between the type or site of FH mutation and any aspect of the MCUL phenotype. Biochemical assay for reduced FH functional activity in the germline of MCUL patients can indicate carriers of FH mutations with high sensitivity and specificity, and can detect reduced FH activity in some patients without detectable FH mutations. We conclude that MCUL is probably a genetically homogeneous tumour predisposition syndrome, primarily resulting from absent or severely reduced fumarase activity, with currently unknown functional consequences for the smooth muscle or kidney cell.
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PMID:Genetic and functional analyses of FH mutations in multiple cutaneous and uterine leiomyomatosis, hereditary leiomyomatosis and renal cancer, and fumarate hydratase deficiency. 1276 Oct 39

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant disorder characterized by smooth-muscle tumors of the skin and uterus and/or renal cancer. Although the identification of germline mutations in the fumarate hydratase (FH) gene in European families supports it as the susceptibility gene for HLRCC, its role in families in North America has not been studied. We screened for germline mutations in FH in 35 families with cutaneous leiomyomas. Sequence analysis revealed mutations in FH in 31 families (89%). Twenty different mutations in FH were identified, of which 18 were novel. Of these 20 mutations, 2 were insertions, 5 were small deletions that caused frameshifts leading to premature truncation of the protein, and 13 were missense mutations. Eleven unrelated families shared a common mutation: R190H. Eighty-one individuals (47 women and 34 men) had cutaneous leiomyomas. Ninety-eight percent (46/47) of women with cutaneous leiomyomas also had uterine leiomyomas. Eighty-nine percent (41/46) of women with cutaneous and uterine leiomyomas had a total hysterectomy, 44% at age < or =30 years. We identified 13 individuals in 5 families with unilateral and solitary renal tumors. Seven individuals from four families had papillary type II renal cell carcinoma, and another individual from one of these families had collecting duct carcinoma of the kidney. The present study shows that mutations in FH are associated with HLRCC in North America. HLRCC is associated with clinically significant uterine fibroids and aggressive renal tumors. The present study also expands the histologic spectrum of renal tumors and FH mutations associated with HLRCC.
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PMID:Mutations in the fumarate hydratase gene cause hereditary leiomyomatosis and renal cell cancer in families in North America. 1277 87

Metastatic renal cell carcinoma (RCC) is a disease that is highly resistant to systemic chemotherapy. Responses to combination chemotherapy have been reported in patients with collecting duct carcinoma and the sarcomatoid variant of renal cancer. Clinical trials combining chemotherapy with biologic response modifiers have not resulted in significant advances in the treatment of RCC. Patients with advanced local or metastatic RCC should be offered investigational therapeutic options. The identification of novel agents with significantly improved antitumor activity remains a high priority in the treatment of this disease.
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PMID:Chemotherapeutic strategies for renal cell carcinoma. 1295 58

The fragile histidine triad (FHIT) gene located in human chromosome 3p14.2 is a candidate tumor suppressor gene that has a diadenosine triphosphate (Ap3A) hydrolase activity, but its role in carcinogenesis remains uncertain. To investigate the role of FHIT in normal cells, specific polyclonal antibodies to recombinant rat FHIT protein were generated. Immunoblot analysis revealed the 17-kd FHIT protein was most abundantly expressed in kidney and liver, whereas heart, skeletal muscle, and adrenal gland expressed trace amounts. In kidney, immunohistochemical staining was strongly observed in distal convoluted tubule and collecting duct during postnatal growth period. By a nested reverse transcription-PCR analysis of FHIT from 2 human kidney cancer cell lines, four abnormal-sized FHIT transcripts, with deletion and/or insertion, were detected. These were derived from the results of exon skipping, and/or insertion of FHIT intron 5 sequence, or selection of cryptic splice site within the FHIT cDNA sequence 179-180. Taken together, our data indicate that FHIT expression is frequently altered in human kidney cancer cell lines by alternative splicing, and suggest that the FHIT protein may play a pivotal role in regulating intracellular metabolism of the distal convoluted tubule and collecting duct in maturity.
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PMID:Expression of the fragile histidine triad gene in normal rat tissues and human kidney cancer cell lines. 1508 May 5

Hereditary leiomyomatosis and renal cell cancer (HLRCC) (MIM 605839) is a recently identified autosomal dominant tumor susceptibility syndrome characterized by predisposition to benign leiomyomas of the skin and the uterus (fibroids, myomas). Susceptibility to early-onset renal cell carcinoma and uterine leiomyosarcoma is present in a subset of families. Renal cell carcinomas are typically solitary and aggressive tumors displaying papillary type 2 or collecting duct histology. The disease predisposing gene was identified as fumarate hydratase (fumarase, FH) (MIM 136850). FH encodes an enzyme that operates in the mitochondrial Krebs cycle being thus involved in cellular energy metabolism. The recent discovery of HLRCC and the predisposing gene FH has increased the present knowledge of hereditary renal cancer and enabled identification of the predisposed individuals. This review provides the present knowledge of the clinical, histopathological, and molecular features of HLRCC. Future prospects related to studies on the phenotype and molecular biology of HLRCC will also be discussed.
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PMID:Hereditary leiomyomatosis and renal cell cancer (HLRCC). 1557 34

Renal collecting duct carcinoma is a rare form of renal cancer known to present in a variety of ways that are often similar to presentations of renal cell carcinoma or transitional cell carcinoma. Little information is available concerning the use of cytology and fluorescence in situ hybridization (FISH) in the diagnosis of collecting duct carcinoma. The available literature contains cases with atypical cytology, but no collecting duct carcinoma cases with abnormal FISH results have been reported. We report a case of renal collecting duct carcinoma presenting with atypical cytology and abnormal FISH results.
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PMID:Abnormal fluorescence in situ hybridization analysis in collecting duct carcinoma. 1628 48

The purpose of classifying neoplasias is to recognize groups with similar progress and prognosis and, if possible, receiving the same treatment. This is why those classifications are systematically being submitted to review and improvement through the new technologies. Differentiation of various entities in renal cancer has been comparatively fast, as the new genetic and molecular discoveries have confirmed the morphologic criteria of the different cell types, thus making it possible to open new therapeutic pathways. Using the current WHO classification we recognize subtypes with excellent prognosis (Multilocular cystic renal carcinoma, Type I renal papillary carcinoma, Tubular and fusocellular mucinous carcinoma), other very aggressive ones (Bellini's collecting duct carcinoma, Medullary carcinoma), and also that the sarcomatoid transformation, even in small areas, impacts the prognosis negatively. Childhood-characteristic renal carcinomas associated with chromosome translocations have been recognized (genetic fusion TFE3 or TFEB), as well as the family forms of renal carcinoma. Regarding the UICC (International Union Against Cancer) classification, there are a series of aspects under argument (size, venous invasion, microvascular invasion, invasion of the adipous tissue of the renal sinus) that shall be discussed too, since it is possible that some modifications of the TNM might occur in the near future.
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PMID:[Usefulness of the present renal cell carcinoma classifications]. 1683 9

Cilia are specialized organelles that play an important role in several biological processes, including mechanosensation, photoperception, and osmosignaling. Mutations in proteins localized to cilia have been implicated in a growing number of human diseases. In this study, we demonstrate that the von Hippel-Lindau (VHL) protein (pVHL) is a ciliary protein that controls ciliogenesis in kidney cells. Knockdown of pVHL impeded the formation of cilia in mouse inner medullary collecting duct 3 kidney cells, whereas the expression of pVHL in VHL-negative renal cancer cells rescued the ciliogenesis defect. Using green fluorescent protein-tagged end-binding protein 1 to label microtubule plus ends, we found that pVHL does not affect the microtubule growth rate but is needed to orient the growth of microtubules toward the cell periphery, a prerequisite for the formation of cilia. Furthermore, pVHL interacts with the Par3-Par6-atypical PKC complex, suggesting a mechanism for linking polarity pathways to microtubule capture and ciliogenesis.
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PMID:The von Hippel-Lindau tumor suppressor protein controls ciliogenesis by orienting microtubule growth. 1710 96


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