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)

Prostate cancer is the most common malignant disease in men in western societies. Extracapsular spread of carcinoma is found in approximately half of the patients that are treated by radical prostatectomy. Recently, a new prostate-specific membrane glycoprotein was cloned and sequenced. A highly sensitive and specific nested reverse transcriptase polymerase chain reaction has been developed to detect early occult haematogeneous micrometastatic prostate cells. We analysed venous samples from 17 patients with metastatic prostate cancer using a modified reaction assay. This showed presence of micrometastatic prostate cells in 14 patients. Molecular detection of circulating prostatic epithelial cells could improve clinical staging and treatment of early prostate cancer.
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PMID:[Prostate-specific membrane antigen. A new sensitive molecular indicator in metastasizing prostatic cancer]. 863 73

The introduction of prostatic specific antigen (PSA) assay as an organ-specific marker has totally modified our approach to diseases of the prostate gland. PSA is an exocrine secretion of the normal epithelium of the prostate and any infectious, dystrophic or tumoural processes involving the gland can lead to an increased level in the blood stream. PSA is the most effective means of following the curative effect of treatment for prostate cancer. After radical prostatectomy, PSA should be undetectable with hypersensitive tests (detection threshold < 0.1 ng/ml) 6 weeks after the operation. The persistence or reappearance of the marker in the blood stream is a clear indication of recurrence. A drop off in PSA under laboratory normal levels is an effective marker of the efficacy of hormone treatment for metastatic cancer but does not signify cure. There are still several points of debate. Serum PSA does increase with prostate volume but there is no apparent linear relationship. PSA is an important factor in early diagnosis of prostate cancer but must always be interpreted in light of the patient's age. In patients treated for cancer of the prostate, PSA is insufficient to determine tumour extension. The relationship between the PSA level and prostate volume could be a way of suspecting cancer, but the operator-dependent results of echography hinder application. Finally, search for circulating secretory cells with reverse transcriptase polymerase chain reactions still requires validation, but could be used for assessing cancer extension.
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PMID:[Prostate-specific antigen or PSA. Facts and probabilities]. 854 44

Transforming growth factor beta 1 (TGF-beta 1), a potential regulator of growth of prostate cancer cells, exerts its effects through interaction with membrane receptors. In the present study, an attempt was made to establish a correlation between TGF-beta 1 sensitivity and TGF-beta receptor expression in three prostate cancer cell lines (PC3, DU145, and LNCaP). In a dose-dependent manner, TGF-beta 1 inhibited the proliferation of PC3 and DU145 cells but not LNCaP cells. Since TGF-beta signals through a heteromeric complex composed of TGF-beta receptors type II and type I, the expression of these receptors was investigated by Western blot analysis and reverse transcriptase-PCR. These studies demonstrated that all three prostate cancer cell lines express type II receptor. In contrast, type I receptor was detected only in the TGF-beta 1-sensitive PC3 and DU145 cells but not in the TGF-beta 1-insensitive LNCaP cells. To investigate the possibility that the undetectable expression of type I receptor in LNCaP cells is due to a change in the respective gene, Southern blot analysis was performed. The result demonstrated that there was a genetic change in type I receptor gene in these cells. Subsequently, when LNCaP cells were transiently transfected with T beta R-I cDNA, sensitivity to TGF-beta 1 was restored. These observations indicate that LNCaP cells contain a defective T beta R-I gene which rendered these cells insensitive to the action of TGF-beta 1.
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PMID:Genetic change in transforming growth factor beta (TGF-beta) receptor type I gene correlates with insensitivity to TGF-beta 1 in human prostate cancer cells. 854 72

We have studied the response to oestrogen and expression of oestrogen receptors in responsive LNCaP and androgen non-responsive PC3 human prostate cancer cell lines. Growth of LNCaP cells is significantly stimulated by physiological concentrations of oestradiol; this growth increase appears to be comparable to that induced by either testosterone or dihydrotestosterone. In contrast, oestradiol significantly inhibits the proliferation of PC3 cells. We also present novel evidence for functional oestrogen binding in LNCaP cells. This evidence was first obtained by means of radioligand binding assays and was further corroborated using: (a) immunocytochemical analysis of oestrogen and progesterone receptors; (b) reverse transcriptase polymerase chain reaction of oestrogen receptor mRNAs; and (c) immunofluorescence of the 27 kDa heat shock protein (Hsp27), which has been reported to be a marker of functional oestrogen receptors. There appeared to be significantly and consistently lower levels of oestrogen receptor expressed in PC3 cells than in LNCaP cells. The observation that oestradiol-induced growth of LNCaP cells is completely reversed by the pure anti-oestrogen ICI 182,780 clearly implies that the biological response of these cells to oestradiol is mediated mainly via its own receptor. On the other hand, use of a neutralizing antibody against transforming growth factor (TGF)-beta 1 results in a remarkable increase in the growth of PC3 cells; this effect is almost completely abolished after the addition of oestradiol. This suggests that the oestradiol-induced growth inhibition may be mediated by TGF-beta 1. These results suggest that the current model for hormone-dependence of human prostatic carcinoma should be revised. This is of special concern, because recent data indicate that prostate cancer has become the most prevalent cancer and the second principal cause of cancer death in western countries.
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PMID:Human prostate cancer: a direct role for oestrogens. 858 3

Estramustine (EM), an antimicrotubule agent, is effective against hormone-refractory prostate cancer when used in combination with vinblastine or paclitaxel. To understand the effect of EM on beta-tubulin, a cellular target for this class of drugs, human prostate carcinoma cells (DU-145) were made resistant to EM, and two cell lines were selected at 12- (EM-12) and 15-microMolar (EM-15) concentrations of the drug. These cell lines exhibited 8- to 9-fold resistance to EM and 2- to 4-fold cross-resistance to paclitaxel. Immunofluorescent staining of the cells with beta-tubulin isotype-specific antibodies showed an approximately 6-fold increase in the beta(III)-tubulin levels and moderate increase in overall beta-tubulin levels in EM-resistant cells when compared to DU-145 cells. This increase of beta(III) isotype was confirmed by Western analysis. A reverse transcriptase-PCR assay was also employed using beta-tubulin isotype-specific primers to quantify beta-tubulin isotype RNA. A 4-fold increase in beta(III) and a 3-fold increase in beta(IV alpha) transcript were seen in both EM-resistant cell lines. These results indicate that overexpression of specific beta-tubulin isotypes may play a role in the cellular defense against EM and other antimicrotubule agents.
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PMID:Increase of beta(III)- and beta(IVa)-tubulin isotopes in human prostate carcinoma cells as a result of estramustine resistance. 865 1

The presence of prostate-specific antigen (PSA)-positive cells has previously been demonstrated in the peripheral blood of prostate cancer patients by flow cytometry (FC), but the identity of these cells has not been established. In this study, the reverse transcriptase polymerase chain reaction (RT-PCR) was compared with analytical FC in an attempt to detect and characterise these cells. Peripheral blood was obtained from 12 patients with newly diagnosed and untreated prostate cancer and five controls. Nine of the 12 patients with prostate cancer (75%) had circulating PSA-positive cells as shown by FC. Only one of those patients (11.1%) was found to express PSA mRNA by RT-PCR. The absence of PSA mRNA in the majority of samples showing PSA-positive cells suggests that they do not represent haematogenous micrometastases. PSA-positive cells in the blood could represent monocytes that express PSA, either following binding/phagocytosis of free serum PSA or phagocytosis of tumour cells.
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PMID:Detection of circulating prostate-specific antigen-positive cells in patients with prostate cancer by flow cytometry and reverse transcription polymerase chain reaction. 869 55

Among women with node-negative breast cancer and small tumours, it is important to identify those with tumours that will recur, so that they may receive adjuvant therapy, while sparing those with tumours that will not recur the hazards of adjuvant treatment. A reverse transcriptase-polymerase chain reaction (RT-PCR) for prostate-specific antigen (PSA) may be used to identify circulating metastatic cells in patients with prostate cancer. Approximately 30% of breast cancer cells also produce PSA. Therefore, we tested the PSA RT-PCR assay on blood specimens from women with breast cancer. We evaluated 78 women at Mount Sinai Medical Center with histologically confirmed breast cancer. Venous blood (5 cm3) from the women was collected in ethylene diaminetetraacetic acid (EDTA)-treated collection tubes and approximately 400 ng of RNA from each sample was subjected to an RT-PCR. We were able to detect the amplified PSA fragment in 18 of 78 women with breast cancer; 7 of the 18 women with the PSA fragment had localised, small, node-negative tumours, both oestrogen receptor (ER) positive and ER negative. We could not detect the amplified PSA fragment in 20 normal women and 22 normal men. We conclude that PSA RT-PCR may be a useful method for determining the presence of circulating metastatic cells in some women with node-negative breast cancer, and therefore the potential for these women to develop recurrent disease and thus benefit from adjuvant therapy.
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PMID:Reverse transcriptase-polymerase chain reaction for prostate-specific antigen may be a prognostic indicator in breast cancer. 882 51

We have developed a highly sensitive method to detect pelvic lymph node metastasis using the reverse transcriptase-polymerase chain reaction (RT-PCR) with primers specific for prostate-specific antigen (PSA) gene. Fine needle aspiration biopsy (FNAB) of pelvic lymph nodes was performed in 24 patients with prostate cancer. Each aspirated sample (0.05-0.1 ml) was divided into 2 parts; one for RNA extraction and RT-PCR to detect the fragment of PSA mRNA, and the other to smear on a slide glass for conventional cytology. The PSA gene was detected by RT-PCR in 11 FNAB samples which included not only all 6 cytologically positive and 2 cytologically class III cases but also 3 of 16 cytologically negative cases. The PSA gene was not detected by RT-PCR of FNAB samples in any of the 20 cases of bladder cancer. Thus RT-PCR for detection of the PSA gene in FNAB samples may be useful as a new diagnostic technique for detection of early lymph node metastasis in prostate cancer and an additional tool for cytological diagnosis of prostate cancer.
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PMID:[Genetic diagnosis of pelvic lymph node metastasis using fine needle aspiration samples in prostate cancer]. 895 75

We detected micrometastatic prostate cancer cells in lymph nodes and bone marrow using reverse transcriptase-polymerase chain reaction (RT-PCT) specific for prostate-specific antigen (PSA). RT-PCR revealed PSA mRNA in two lymph nodes obtained from two patients with negative histological and immunohistochemical analyses for lymph node metastases. Of 26 patients with negative bone scan imaging, 7 had PSA mRNA detected in the bone marrow by RT-PCR. The RT-PCR will be a relevant tool to allow a more accurate clinical assessment of lymph node and bone metastases in patients with prostate cancer.
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PMID:[Molecular approach to detection of micrometastatic prostatic cancer cells in the lymph nodes and the bone marrow]. 895 76

We have used a reverse transcriptase-polymerase chain reaction assay for prostate specific antigen (PSA) expression to detect hematogenous microdissemination in patients with prostate cancer. Thirty-nine consecutive patients with prostate cancer were surveyed. Nineteen patients (48.7%) were positive for PSA-expressing cells in this assay. Positivity rates by stage were as follows: stage A1-0/1, A2-0/2, B-2/6, C-2/9, D0-3/3, D1-1/4, D2-11/14. In clinically organ-confined cancers with a positive assay result, two stage C patients subsequently developed bone metastasis, while two stage B patients who were positive had no evidence of disease progression. In patients with a negative assay result, 3 of the 3 stage A, 3 of the 4 stage B, and 6 of the 7 stage C patients did not develop hematogenous dissemination during the follow-up period. Molecular assay for hematogenous microdissemination of prostate cancer cells provides an opportunity for earlier detection of disseminated disease and may have prognostic value.
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PMID:[Molecular staging of hematogenous microdissemination of prostate cancer cells]. 895 77


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