Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the distribution of lesions and Hu antigen expression in two autopsied cases of anti-Hu antibody-positive paraneoplastic sensory neuronopathy (carcinomatous subacute sensory neuropathy). Pathological changes in both patients were limited to the primary sensory neurons, some of the sympathetic ganglia and hippocampal regions. The lesions showed a multifocal distribution that differed among the spinal segmental levels and in the individual dorsal root ganglia as well as in the nerve fascicles. Western blot analysis of the patients' serum revealed that Hu antigens were extensively and widely expressed throughout the central nervous system, sensory and sympathetic ganglia and cancer cells, but not in the non-neural visceral tissues. Reverse transcriptase-polymerase chain reaction also showed that the Hu D, Hu C, Hel-N1 and Hel-N2 mRNAs were extensively and widely expressed through the neural tissues and cancer cells, but not in the visceral tissues. Thus, the distribution of antigen expression was very different from that of the lesions. Taken together with the distribution of lesions and Hu antigen expression, it is suggested that factors other than anti-Hu antibodies are also involved in the pathogenesis of this neuronopathy.
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PMID:Tissue distribution of pathological lesions and Hu antigen expression in paraneoplastic sensory neuronopathy. 965 Jul 57

Estramustine (EM) is an anti-microtubule drug used in the treatment of hormone-refractory advanced prostate cancer. Since microtubules are the targets for EM cytotoxicity, we investigated the effects of EM on the microtubule-associated protein tau to determine what role it may play in drug resistance. We have compared tau expression in human prostate cancer cells (DU145) and an EM-resistant derived cell line (E4). Reverse transcriptase polymerase chain reaction has established that tau is expressed in both cell lines but increased 1.9-fold in E4 compared with DU145 cells. This result was confirmed at the protein level by Western blotting. Tau is a phosphoprotein, most of its reported phosphorylation sites being serine or threonine residues. We have shown, however, that tau is also phosphorylated at tyrosine residues in DU145 cells and that the phosphotyrosine level of tau is significantly increased in E4 cells. Moreover, DU145 cells exposed to short term micromolar drug concentrations enter a phase of microtubule depolymerization, display an increased level of tau phosphorylation and follow a pattern similar to that observed in EM-resistant E4 cells. EM is therefore able to induce a very rapid change in the posttranslational state of tau. Our results show that the acquisition of EM resistance in E4 cells, which is accompanied by changes at the tubulin level, is also associated with important changes in tau expression and phosphorylation.
Int J Cancer 1998 Aug 12
PMID:Estramustine resistance correlates with tau over-expression in human prostatic carcinoma cells. 967 68

Progestogen suppresses the progression of endometrial cancer and has an important effect on the secretory change of human endometrium. We characterized the progestogen-induced alterations of gene expression in a human endometrial-cancer cell line using a mRNA differential-display reverse-transcriptase-polymerase-chain-reaction (DDRT-PCR) method. After 5-day incubation of Ishikawa endometrial-cancer cells, with or without 100 nM medroxyprogesterone acetate (M PA), total RNA was isolated from confluent cells. We identified 8 candidate genes by mRNA differential display by screening up to approximately 3,000 mRNA species. Among these, 2 genes named T21A and T21B showed a decrease in mRNA by MPA treatment when analyzed by Northern blot. Nucleotide sequence showed that clone T21A was part of human mitochondrial short-chain enoyl-CoA hydratase cDNA. The other clone, T21B, showed no homology with any known nucleotide sequences. Northern-blot analysis using T21A and T21B clones as probes showed a decrease in mRNA in human endometrium from the luteal stage, with high serum estradiol and progesterone levels, as compared with that from the early follicular stage, with low serum estradiol and progesterone levels, and that from the pre-ovulatory stage with high serum estradiol and low progesterone levels. These findings suggest that mRNA DDRT-PCR could be used to identify the candidate genes regulated by progestogen in human endometrial cancer and in normal human endometrium.
Int J Cancer 1998 Sep 25
PMID:Messenger RNA differential display reverse-transcriptase-polymerase-chain-reaction analysis of a progestogen-suppressive gene in a human endometrial-cancer cell line. 972 4

We report here a 15-year-old boy with an intraabdominal desmoplastic small round cell tumor (DSRCT). Cytogenetic analysis of the tumor cells showed the chromosomal translocation (11;22). Reverse-transcriptase polymerase chain reaction and sequencing analysis revealed a chimeric transcriptional message of the EWS gene exon 10 fused to the WT1 gene exon 8. The typical chimeric transcript seen in DSRCT is an in-frame fusion of EWS exon 7 to WT1 exon 8. The tumor in this case had a novel and longer chimeric transcript, which should be a potent transcription factor. Genetic analysis is a very powerful and specific aid in the differential diagnosis of small round cell tumors.
Cancer Genet Cytogenet 1998 Oct 15
PMID:Novel breakpoints of the EWS gene and the WT1 gene in a desmoplastic small round cell tumor. 979 82

A 40-year-old man had chronic myeloid leukemia (CML) and an apparently normal karyotype. Fluorescence in situ hybridization with a BCR/ABL1-S probe, which is formatted to display a BCR/ABL fusion signal on chromosome 22, gave a positive fusion signal on a chromosome 9. Therefore this patient has a BCR/ABL fusion gene on chromosome 9. The BCR/ABL1-D probe, formatted to display a fluorescent signal for both the reciprocal products of a 9/22 rearrangement, gave a positive fusion signal on the derivatives 9 and 22. These findings favor either a cryptic reciprocal exchange between BCR and ABL loci or the reversal of a Philadelphia translocation. An insertion of BCR next to ABL is ruled out. The reverse-transcriptase polymerase chain reaction provided molecular evidence that a typical CML chimeric product resulting from a fusion of BCR exon 2 with C-ABL exon II, a2b2, is present.
Cancer Genet Cytogenet 1998 Nov
PMID:A Philadelphia-negative chronic myeloid leukemia with a BCR/ABL fusion gene on chromosome 9. 980 34

Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus which establishes life-long latency in the B-lymphocytes of infected individuals. Epstein-Barr virus is associated with Hodgkin's disease, AIDS-associated lymphoma and post-transplant lymphoproliferative disease (PTLD). In PTLD, the onset of malignancy correlates with a rise in EBV load. The relationship between malignancy and EBV load in other EBV-associated malignancies is not known. Epstein-Bar virus latency is associated with the expression of a limited set of viral transcripts. The most numerous of these are the EBERs (Epstein-Barr early RNAs). The high copy number of the EBERs in each latently infected cell led the author to combine serial dilution of lymphocytes with reverse transcriptase polymerase chain reaction (RT-PCR) for EBER-1 as a means to rapidly quantitate EBV load. The highest viral load was seen in a bone marrow transplant patient, where one in 3906 lymphocytes harboured EBV. Elevated viral load was seen in two solid-organ transplant patients. Viral loads in healthy volunteers ranged from less than one in 1x10(6) to one in 6.25x10(4). Reverse transcriptase polymerase chain reaction for EBER-1 in serial lymphocyte dilutions should allow the relationship of EBV load and malignancy to be examined in a number of disease settings and should also provide a quantitative picture of the impact of anti-viral therapy.
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PMID:Determination of Epstein-Barr virus (EBV) load by RT-PCR and cellular dilution. 984 61

Circulating tumour cells in the peripheral blood may be important for haematogenous spread of malignant disease. Monitoring these cells may therefore be of prognostic value. Reverse transcriptase-polymerase chain reaction (RT-PCR)-based assays to detect occult neoplastic cells offer the highest sensitivity for the study of tumour dissemination and minimal residual disease. This review summarises technical considerations and clinical investigations in melanoma patients of various disease stages. The clinical data are promising, but to clearly define the clinical usefulness of messenger RNA (mRNA) tumour markers, methodological issues must be resolved and the clinical value must be assessed prospectively in sufficiently large patient cohorts.
Eur J Cancer 1998 Jul
PMID:New prognostic factors in melanoma: mRNA tumour markers. 984 8

Loss of sequences from human chromosome 10q has been reported in several different cancers. Recently, a second candidate tumour-suppressor gene, DMBT1, was identified in this chromosomal region. We studied the mRNA expression and homozygous deletion of this gene in human oesophageal, gastric and colon cancers. Reverse transcriptase polymerase chain reaction (RT-PCR) amplification demonstrated that 23 (53.5%) of 43 oesophageal, 5 (12.5%) of 40 gastric, and 4 (16.7%) of 24 colorectal cancer cases showed an apparent reduction in DMBT1 mRNA in tumour tissues compared with paired normal tissues. Twelve out of 15 oesophageal cancer cell lines also showed no expression. We next studied homozygous deletions within the DMBT1 gene in oesophageal cancers by using duplex PCR. Consequently, it was recognized in five (11.6%) of the primary tumours and two (13.3%) of the cell lines. These findings suggest that DMBT1 may act as a tumour-suppressor gene not only in brain tumours but also in gastrointestinal cancers, especially in oesophageal cancers.
Br J Cancer 1999 Jan
PMID:Lack of DMBT1 expression in oesophageal, gastric and colon cancers. 988 59

The kinetics of non treated and especially of treated HIV1 is compared to that of non treated and of treated cancer cells. Contrary to Skipper's scheme, based on constancy of cancer cell proliferation or post-chemotherapy decrease slope, the same chemotherapy successive cycles decrease in fact less and less the proportion of cell number reduction, and the hope of killing the "last cell" is a utopian concept. Hence, the very poor global benefit in cancer medicine registered in the last 50 years. The only cures are seen in child tumors and young adults testis cancer: the immunity reaction being stronger before 40 years of age than after 40 may explain this difference with age. The a priori systematic opposition to active immunotherapy of cancer from some authorities has been a grave fault. Such fault should not be committed for the treatment of HIV1-AIDS complex. The continuous HIV1 so called intensive virostatic chemotherapy is complicated by severe toxicities, and resistances of relapses and virus re-activation when it must be discontinued. The widely accepted triple therapy only affects two virus targets (retro-transcriptase and virus protease), which is insufficient, as we have shown. We have also observed that the constant and most rapid VL decrease to < 200 or < 20 RNA copies/mL is obtained when four virus targets are affected, including some concerning DNA provirus (which is the case of acriflavine and methylhydroxy-ellipticine). As in acute lymphoid leukemia, two treatment phases can be distinguished: a) the VL reduction to 20 copies; b) the maintenance of the residual < 20 copies of viruses. Excellent results as far as VL decrease and maintenance at < 20 copies have been obtained with a follow-up between 1 1/2 and 6 years, without any toxicity nor global resistance, with combinations of four drugs affecting four viral targets, applied in short (3 week) sequences, different from each others owing to drug rotation. This can be compared with the 65% remission rate obtained with alternative different cycles of cancer chemotherapy in tumors resistant to conventional modalities. The possibility of repeating for ten patients the evaluation of viral load and of immunologic parameters has allowed us to discover that some VL decrease curves are fractal. As well, maintenance 20 copies are not rarely interrupted by short and reversible HIV1 rebounds as those we had described in "cured" acute lymphoid leukemia patients. Of utmost importance, all HIV1 rebounds were associated with the presence of one cofactor: chimerism, chronic hepatitis, CMV, herpes 8, herpes 6, and influenza are those we observed. The problem today is not to "kill the last tumor cell in cancer" or "the last HIV1 particle" in HIV1-AIDS complex. It is to keep the residual cells or virus in latency. Active immunotherapy and other biologic interventions, such as hypermethylation, should be studied in this aim, as they are also able to do so.
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PMID:The kinetics of cancer cells and of HIV1: the problems of cell and virus rebounds and of latency. 992 9

The receptor for hyaluronan (HA)-mediated motility (RHAMM) controls motility by malignant cells in myeloma and is abnormally expressed on the surface of most malignant B and plasma cells in blood or bone marrow (BM) of patients with multiple myeloma (MM). RHAMM cDNA was cloned and sequenced from the malignant B and plasma cells comprising the myeloma B lineage hierarchy. Three distinct RHAMM gene products, RHAMMFL, RHAMM-48, and RHAMM-147, were cloned from MM B and plasma cells. RHAMMFL was 99% homologous to the published sequence of RHAMM. RHAMM-48 and RHAMM-147 variants align with RHAMMFL, but are characterized by sequence deletions of 48 bp (16 amino acids [aa]) and 147 bp (49 aa), respectively. The relative frequency of these RHAMM transcripts in MM plasma cells was determined by cloning of reverse-transcriptase polymerase chain reaction (RT-PCR) products amplified from MM plasma cells. Of 115 randomly picked clones, 49% were RHAMMFL, 47% were RHAMM-48, and 4% were RHAMM-147. All of the detected RHAMM variants contain exon 4, which is alternatively spliced in murine RHAMM, and had only a single copy of the exon 8 repeat sequence detected in murine RHAMM. RT-PCR analysis of sorted blood or BM cells from 22 MM patients showed that overexpression of RHAMM variants is characteristic of MM B cells and BM plasma cells in all patients tested. RHAMM also appeared to be overexpressed in B lymphoma and B-chronic lymphocytic leukemia (CLL) cells. In B cells from normal donors, RHAMMFL was only weakly detectable in resting B cells from five of eight normal donors or in chronically activated B cells from three patients with Crohn's disease. RHAMM-48 was detectable in B cells from one of eight normal donors, but was undetectable in B cells of three donors with Crohn's disease. RHAMM-147 was undetectable in normal and Crohn's disease B cells. In situ RT-PCR was used to determine the number of individual cells with aggregate RHAMM transcripts. For six patients, 29% of BM plasma cells and 12% of MM B cells had detectable RHAMM transcripts, while for five normal donors, only 1. 2% of B cells expressed RHAMM transcripts. This work suggests that RHAMMFL, RHAMM-48, and RHAMM-147 splice variants are overexpressed in MM and other B lymphocyte malignancies relative to resting or in vivo-activated B cells, raising the possibility that RHAMM and its variants may contribute to the malignant process in B-cell malignancies such as lymphoma, CLL, and MM.
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PMID:Overexpression of the receptor for hyaluronan-mediated motility (RHAMM) characterizes the malignant clone in multiple myeloma: identification of three distinct RHAMM variants. 1002 98


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