Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To obtain insight into the secretion pattern of human chorionic gonadotropin (hCG) and its free subunits, hCG alpha and hCG beta, in vivo, we analyzed hydrocele fluids of 13 patients with testicular cancer and correlated the respective values to those of cubital vein and testicular vein serum. As a control population, patients with nonmalignant hydroceles (n = 11) were studied. Analyses were performed with a set of highly sensitive and specific time-resolved fluoroimmunoassays based on our own panel of monoclonal antibodies. In the collective of testicular cancer patients, increased hydrocele levels of either hCG or free hCG alpha or free hCG beta were observed in 77, 54, and 92% of cases; the corresponding percentages for cubital vein serum were 62, 23, and 31%. The cubital vein ratio of hCG:hCG alpha (546:1) and hCG:hCG beta (51:1) decreased to 64:1 and to 7:1 in the hydrocele fluids. Surprisingly, hydrocele fluids of five patients with pure seminoma, who were negative for the three markers in the periphery, revealed an elevation of free hCG beta in all cases, while hCG alpha and holo-hCG were elevated twice. Final proof that hCG beta and hCG alpha are indeed produced by these previously termed "marker negative" seminomas has been achieved by reverse transcriptase-polymerase chain reaction with primers specific for the alpha-subunit and the four most abundantly transcribed hCG beta genes 3, 5, 7, and 8. From these data, we conclude that: (alpha) seminomatous and nonseminomatous testicular cancers, irrespective of histology, secrete hCG and its free subunits; (b) the amount of free subunits being secreted in vivo by these tumors has been underestimated; and (c) the classification in marker-positive and marker-negative testicular cancer should be reconsidered.
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PMID:Human chorionic gonadotropin (hCG) and its free subunits in hydrocele fluids and neoplastic tissue of testicular cancer patients: insights into the in vivo hCG-secretion pattern. 792 24

Despite recent extensive immunohistochemical studies, the expression patterns of CD44 in testicular germ cell tumors are still controversial. In the present study, we investigated the CD44 gene expression in 40 specimens including 18 seminomas, 16 nonseminomatous germ cell tumors (NSGCT), and 6 normal testes by reverse transcriptase-polymerase chain reaction and Western blotting. Reverse transcriptase-polymerase chain reaction analysis revealed that the standard CD44 isoform (CD44s) was expressed in all of the specimens, whereas the variant CD44 isoforms were highly expressed in NSGCTs but barely detectable in seminomas and normal testes. In addition, we confirmed by direct DNA sequence analysis that the predominantly expressed variant isoform in NSGCTs was CD44v8-10. In germ cell tumors, these results were paralleled in Western blot analysis; that is, CD44s protein was expressed in all of the tumor specimens, whereas high molecular weight variant isoforms were expressed only in NSGCTs. However, at the protein level, no detectable CD44 was expressed in normal testes. These findings show that the combined assessment of CD44 expression patterns at both the RNA and protein levels enables us to distinguish among seminoma, NSGCT, and normal testis specimens; hence, it could serve as a useful practical adjunct to conventional diagnostic methods for testicular germ cell tumors.
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PMID:Expression patterns of CD44 adhesion molecule in testicular germ cell tumors and normal testes. 958 83

Growth hormone (GH) and placental lactogen (PL) gene transcription patterns in testicular germ cell tumors (GCT) and normal testicular tissue were comparatively investigated to identify GH/PL gene products associated with the development of GCT. This was done by nondiscriminative reverse transcriptase-polymerase chain reaction (RT-PCR), amplifying all major transcripts of any of the 5 GH/PL genes--GH-N(ormal), GH-V(ariant), PL-A, PL-B, PL-L(ike)--and subsequent analytical restriction enzyme analyses of 5'-end radioactively labeled cDNA. Surprisingly, all nonseminomatous GCT (NSGCT; n = 9) expressed GH-N, PL-A/B, and PL-L transcripts (9 of 9). Seminoma (n = 7) showed a distinctly unique pattern of GH-N and PL-A/B. GH-V products, which are hallmarks of the normal healthy testis, were not detected in any testicular cancer specimen (0 of 16). The fact that both seminomatous and NSGCT showed alterations in the same gene cluster indicates a pathogenetic relationship. Two choriocarcinoma cell lines of conceptus origin, BeWo and JAR, clearly differing from the male counterparts, exhibited a placental-derived pattern of PL-A/B and GH-V. Obviously, profound differences exist between conceptus and male germ cell GH/PL gene cluster transcription. In summary, the unique testicular pattern of GH/PL gene expression changes significantly and in directed ways with malignancy. Loss of GH-V gene expression in testicular GCT compared with normal testis and loss (seminoma) or mutation (NSGCT) of PLL gene products might have significance in terms of the relationship between these tumors and for testicular GCT development.
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PMID:The testis-specific expression pattern of the growth hormone/placental lactogen (GH/PL) gene cluster changes with malignancy. 1053 68

In humans, alkaline phosphatases are encoded by one tissue-non-specific alkaline phosphatase (TNAP) gene and three tissue-specific alkaline phosphatase genes, intestinal, placental (PLAP), and germ cell-specific alkaline phosphatase (GCAP). Although the presence of alkaline phosphatases in testicular germ cell tumours (TGCTs) of adolescents and adults has been utilized for both detection and patient monitoring, it is not known in detail which isozymes are expressed. Since alkaline phosphatase is detected in carcinoma in situ (CIS), the common precursor of all TGCTs, it might provide a marker for the early diagnosis of TGCTs. Testicular cancers of germ cell and non-germ cell origin along with testicular parenchyma with and without CIS have been analysed for the expression of the different alkaline phosphatase isozymes. Antibodies to TNAP and PLAP/GCAP showed positivity in CIS, seminoma, and embryonal carcinoma. The heterogeneous staining pattern detected in frozen tissue sections was similar to the pattern found in formalin-fixed, paraffin-embedded material, indicating a biological phenomenon and not a handling artefact. Since PLAP and GCAP cannot be distinguished using immunohistochemistry, the expression of these isozymes was studied at the molecular level using a reverse transcriptase-polymerase chain reaction (RT-PCR) approach, in combination with a primer extension assay. The results show that CIS and seminoma predominantly express GCAP, while in embryonal carcinoma the expression of GCAP versus PLAP varies. Due to the presence of alkaline phosphatase transcripts in normal testicular parenchyma, an RT-PCR-based analysis of alkaline phosphatase is not informative for the early detection of TGCTs in biopsy samples.
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PMID:Heterogeneity in alkaline phosphatase isozyme expression in human testicular germ cell tumours: An enzyme-/immunohistochemical and molecular analysis. 1054 81

Testicular germ cell tumors are important neoplasms and seminoma accounts for 40 to 50% of these tumors. Little is known concerning the molecular events underlying the development of these malignancies. In the present study we used a modified differential display approach to compare gene expression between seminoma and normal testicular parenchyma, both of which are mixed tissues. We first analyzed mRNA (cDNA) expression by differential display and then directly used differentially expressed cDNAs for the synthesis of radiolabeled riboprobes to attribute differential expression to specific cell types in tissue sections by in situ hybridization. Using this approach along with real-time quantitative reverse transcriptase-polymerase chain reaction analysis we found an overexpression of eukaryotic initiation factor 3 p110 mRNA (EIF3S8) in seminoma cells compared to normal germ cells of testicular tubules. The elF3-p110 subunit may promote seminoma development by generally increasing translation leading to enhanced cellular growth and division rates.
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PMID:Eukaryotic initiation factor 3 p110 mRNA is overexpressed in testicular seminomas. 1107 19

Changes in the activities of enzymes related to energy metabolism in the testicular tissues of dogs with seminoma were investigated. The testis was removed surgically from animals anaesthetized with halothane. Cytosolic and mitochondrial fractions were isolated and the total RNA was extracted from testicular homogenates. The activities of enzymes related to energy metabolism were measured and the mRNA of cytosolic malate dehydrogenase (MDH) was investigated by the reverse transcriptase-polymerase chain reaction (RT-PCR). The activities of the glycolytic enzymes glucose-6-phosphate dehydrogenase (G6PD) for the pentose phosphate pathway and malate dehydrogenase (MDH) for the malate-aspartate shuttle, and the expression of the mRNA of cytosolic MDH were significantly increased in the testicular tissues of dogs with seminoma. These enzymatic activities may be useful indicators with which to evaluate changes in the metabolic conditions in testicular tissues of dogs with seminoma.
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PMID:Changes in activities of enzymes related to energy metabolism in testicular tissues of dogs with seminoma. 1221 24

The carcinoma in situ (CIS) cell is the common precursor of nearly all testicular germ cell tumours (TGCT). In a previous study, we examined the gene expression profile of CIS cells and found many features common to embryonic stem cells indicating that initiation of neoplastic transformation into CIS occurs early during foetal life. Progression into an overt tumour, however, typically first happens after puberty, where CIS cells transform into either a seminoma (SEM) or a nonseminoma (N-SEM). Here, we have compared the genome-wide gene expression of CIS cells to that of testicular SEM and a sample containing a mixture of N-SEM components, and analyse the data together with the previously published data on CIS. Genes showing expression in the SEM or N-SEM were selected, in order to identify gene expression markers associated with the progression of CIS cells. The identified markers were verified by reverse transcriptase-polymerase chain reaction and in situ hybridisation in a range of different TGCT samples. Verification showed some interpatient variation, but combined analysis of a range of the identified markers may discriminate TGCT samples as SEMs or N-SEMs. Of particular interest, we found that both DNMT3B (DNA (cytosine-5-)-methyltransferase 3 beta) and DNMT3L (DNA (cytosine-5-)-methyltransferase 3 like) were overexpressed in the N-SEMs, indicating the epigenetic differences between N-SEMs and classical SEM.
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PMID:Genome-wide gene expression profiling of testicular carcinoma in situ progression into overt tumours. 1585 41

Infertility has been stated as a risk factor for testicular cancer; but currently, there is no prognostic indicator of tumor development from the pathologic testis with impaired spermatogenesis. Regenerating proteins are expressed in many human tissues including the testis, and their role in carcinogenesis has been well documented. In the present work, regenerating I messenger RNA and protein expression and cellular protein localization were studied in testicular biopsies of patients with normal (obstructive azoospermia) or impaired spermatogenesis (nonobstructive azoospermia) and in seminoma testis by quantitative reverse transcriptase-polymerase chain reaction, Western blot, and immunofluorescence analyses. No significant differences in regenerating I transcripts were reported between the 3 groups studied. However, regenerating I protein was highly expressed in pure seminoma and in placental-like alkaline phosphatase-positive seminiferous tubules with in situ carcinoma. Regenerating I protein levels measured by Western blotting increased from the placental-like alkaline phosphatase-negative distal region of the seminoma to the pure placental-like alkaline phosphatase-positive tumoral region. Importantly, although cells localized in seminiferous tubules of obstructive azoospermic patients with normal spermatogenesis were very slightly labeled, persisting germ, Sertoli, and myoid cells and fibrous tissues were strongly regenerating I positive in seminiferous tubules of nonobstructive azoospermia. These results suggest the possibility to use regenerating I as a prognostic marker of tumoral development in the infertile testis.
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PMID:Regenerating I messenger RNA and protein expression in the failing human testis: a potential molecular prognostic marker of seminoma. 2168 84

The presence of human chorionic gonadotropin (hCG) positive syncytiotrophoblastic cells (STC) in classic seminoma (CS) is well documented. CS with extensive hCG positive, non-syncytiotrophoblastic tumour cells (without STC) is exceptionally rare. In this study, we present 15 such cases. 168 CSs were retrieved from the Plzen Tumor registry. Cases of mixed germ cell tumors (with CS) and CSs with typical STC were excluded. Cases with completely embedded tumor mass were selected for further study and immunohistochemically examined with anti-hCG. Positive cases were further analyzed by reverse transcriptase polymerase chain reaction. Two groups of hCG-positive CSs were identified. Group 1 comprised 10 patients with a mean patient age of 37.7 years and mean tumor size of 4.96 cm. Eight cases were pT1 (TMN 2009) and 2 cases pT3a. Blood levels of hCG were elevated in 6 of the 10 patients preoperatively. In 2 patients the blood level of hCG was not tested. Mean follow-up period was 6.1 years. No metastatic behavior was noted. All tumors were extensively immunoreactive for hCG in more than 60% of tumor cells. The expression of hCG beta subunit (CGB)-mRNA in tumor tissue was documented. Group 2: Comprised 5 patients with a mean age was 34 years. Mean tumor size was 4.7 cm. Four cases were stage pT1 and 1 case was pT2. The mean follow-up period was 3.1 years. No metastatic behavior was noted. Preoperative blood levels of hCG were elevated in 1/5 of the patient. Strong hCG positivity was limited to scattered single tumor cells distributed throughout the entire tumor. Only weak expression of CGB mRNA was detected. We can conclude that immunohistochemical detection of expression of hCG in CS is not limited to syncytiotrophoblastic cells. In this study, we report two immunohistochemical patterns of hCG expression in classic seminomas: diffuse hCG staining in the majority of tumor cells and scattered hCG-positive cells within the tumor.
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PMID:Choriogonadotropin positive seminoma-a clinicopathological and molecular genetic study of 15 cases. 2448 Apr 32

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