Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 70-year-old Japanese male was first diagnosed as poorly differentiated adenocarcinoma of the prostate with bone metastasis in 1983. He received chemoendocrine therapy with both DESD and HCFU following subcapsular orchiectomy since 1983. As a result of the treatment, the prostate cancer was stabilized. At the end of 1988, the serum levels of PA were elevated. Diagnostic imaging revealed a local recurrence in the prostate. The pathological analysis of the prostate revealed undifferentiated adenocarcinoma. Intraarterial chemotherapy with a reservoir system was carried out. Doses of CDDP, ADM and MTX were 75 mg, 30 mg and 50 mg, respectively. Eight weeks after intraarterial chemotherapy, the regression rate was 60%, and serum PA titer improved to within normal limits. In this case, as the initial clue for suspecting recurrence, periodic detection of PA was useful, and the intraarterial chemotherapy was considered useful for the control of the locally recurrent prostate carcinoma.
 ...
PMID:[A case report of relapsed stage D2 prostate cancer successfully treated with intraarterial chemotherapy]. 171 41

From June 1984 to March 1988, patients with newly diagnosed stage D2 prostate cancer were treated with protocol 1. This comprised oral hormonal agents either diethylstilbestrol diphosphate (Honvan: 300 mg/day) or estramustine phosphate (Estracyt: 560 mg/day), or chlormadinone acetate (Prostal: 100 mg/day), plus intravenous cyclophosphamide (CPM, 0.5-1 g/m2) every 3-4 weeks. From May 1988, protocol 2 was used in a randomized study of castration alone versus castration plus intravenous methotrexate (MTX, 20 mg/m2) every 2 weeks. Forty-nine of 53 patients who underwent the two protocols were evaluable for the response. The response rates according to the NPCP criteria were 92% (11/12) for Honvan, 100% (9/9) for Estracyt, 78% (7/9) for Prostal and castration plus MTX, and 80% (8/10) for castration alone. There were no significant differences among these treatments. The median response duration and survival time (months) were 16 and 44, respectively, for Honvan, 19 and 37 for Estracyt, 12 and 43 for Prostal, 11 and 15 for castration plus MTX, and 13 and 13 for castration alone. The short survival times of the castration alone and castration plus MTX groups were due to a short follow-up period. There were no statistical differences among the oral hormonal agent plus CPM groups. However, the 2-year survival rate (Kaplan-Meier method) was higher in the CPM and MTX groups than in the castration alone group. Survival was longer in the good performance status (P.S.) group than the poor P.S. group (p less than 0.05 by Wilcoxon test) and in the responders than the non-responders (p less than 0.01). Side effects were not excessive in the chemotherapy groups and patient compliance was good.
 ...
PMID:[Treatment of newly diagnosed stage D2 prostatic carcinoma with hormonal therapy alone, or chemotherapy agents in combination with hormones]. 172 34

In this clinical trial of men with advanced prostatic cancer no longer responsive to hormone therapy 189 were randomized to receive estramustine phosphate, methotrexate or cis-platinum. Response evaluations were done in 158 cases. Objective response rates (complete, partial or stabilization of disease) were 34 per cent for estramustine phosphate, 36 per cent for cis-platinum and 41 per cent for methotrexate. Subjective parameters indicated a substantial advantage for pain improvement with methotrexate or cis-platinum over estramustine phosphate. Probabilities of continued response indicated some advantage for methotrexate and median response durations at this time were twice as long for methotrexate (32 weeks) as for cis-platinum (16 weeks), with estramustine phosphate intermediate (23 weeks). Survival rates for the original treatment randomization groups were not different at this time. Side effects of estramustine phosphate consisted primarily of nausea and vomiting and/or anorexia but to a lesser extent than with cis-platinum. These effects were somewhat less for methotrexate, for which the major side effects were stomatitis and leukopenia, as well as hepatic toxicity reflected by elevated serum glutamic oxaloacetic transaminase levels. Other side effects of cis-platinum were less than for methotrexate (no stomatitis), except for signs of renal toxicity (elevations in blood urea nitrogen and serum creatinine), which were greater. Methotrexate had a relatively high level of activity against metastatic, progressive, hormone nonresponsive prostatic cancer, with side effects that were substantial but manageable.
 ...
PMID:Comparison of estramustine phosphate, methotrexate and cis-platinum in patients with advanced, hormone refractory prostate cancer. 634 29

This article is a review of the results of chemotherapy for advanced hormonally-unresponsive prostatic carcinoma. Although the only hope for treatment of these patients is chemotherapy, until recently relatively little emphasis has been placed on chemotherapy of prostatic cancer. Since results of the randomized trial of the National Prostatic Cancer Project in the United States revealed a demonstrable advantage of advanced hormonally-refractory disease, a number of studies has been done and reported. As single chemotherapeutic agent, cyclophosphamide (CPM), 5-fluorouracil (5-FU), Adriamycin (ADM), and Cisplatinum (CDDP) have activity in these patients. Estracyt has been reported very effective, but has been somewhat disappointing in American trials. Several combination chemotherapies have been reported effective, such as CPM + ADM, CPM + ADM + Methotrexate (MTX), and CPM + MTX + 5-FU + Vincristine, Prednisone. Presently, however, there is no evidence that combination chemotherapy in prostatic cancer is better than single-agent chemotherapy. The need for continued effort to search powerful new agent, and to establish more effective combination chemotherapy for prostatic cancer should be emphasized. Furthermore, the importance of randomized and stratified clinical trials, early and late in the course of the disease, is stressed.
 ...
PMID:[Chemotherapy of hormone-unresponsive prostatic cancer and its metastatic foci]. 676 5

A 73-year-old male with low abdominal pain on urination and frequent urination was diagnosed as poorly differentiated adenocarcinoma of prostate. He received endocrine therapy with DESD and bilateral orchiectomy. This treatment was not effective, so he was given intra-arterial infusion chemotherapy with MTX, ADM and CDDP using the reservoir system. After 2 courses of this chemotherapy the regression rate was 75%, and the pathological examination after the chemotherapy revealed no cancer cells. There is no established chemotherapy for prostate cancer at present. Thus this case is very suggestive for the treatment of prostate cancer.
 ...
PMID:[A case report of prostate cancer resistant to endocrine therapy successfully treated with intra-arterial chemotherapy]. 757 95

Recently attention has been focused on the optimal timing of chemotherapy within the treatment regimen for patients with metastatic prostate cancer, i.e., hormonal manipulation, preferably maximal androgen blockage (MAB) consisting of chemical/surgical castration followed by treatment with antiandrogens. We have conducted a randomized prospective clinical trial, investigating the efficacy and toxicity of MAB (orchiectomy followed by flutamide therapy) alone as compared to MAB combined with methotrexate (MTX, 50 mg/m2/week) in 53 patients with newly diagnosed stage IV(M1) prostatic cancer (UICC TNM Classification 1987). The observed remission rates (complete + partial) of 42.3% in the MAB + MTX arm and 29.6% in the MAB arm did not differ significantly. The response rates (complete + partial + stable disease) of 73.1% and 66.7% for MAB + MTX and MAB respectively, also showed no significant difference. Neither progression-free survival (median 18/5 and 23.8 months for MAB + MTX and MAB, respectively) nor overall survival (median: 37.4 and 36.1) months in the MAB + MTX and MAB arm, respectively) could be improved by the addition of MTX to MAB Only the extent of metastatic pain reported by the patients was consistently less under MAB + MTX than under MAB alone (P<0.1). Both treatment regimens were well- tolerated with slightly more undesirable effects in the MAB + MTX arm. Our results do not provide evidence for the achievement of marked gains by combining chemotherapy with endocrine therapy in newly diagnosed patients with stage IV (M1) prostate cancer.
 ...
PMID:Maximal androgen blockade in combination with methotrexate for treatment of metastatic prostate cancer. 860 66

A novel monoclonal antibody has been developed that reacts strongly with human prostatic cancer, especially tumors of high grade. This antibody (7E11C-5) is currently in Phase 3 trials as an imaging agent for metastatic disease. We have cloned the gene that encodes the antigen that is recognized by the 7E11C-5 monoclonal antibody and have designated this unique protein prostate-specific membrane (PSM) antigen. PSM antigen is a putative class II transmembranous glycoprotein exhibiting a molecular size of Mr 94,000. Functionally, class II membrane proteins serve as transport or binding proteins or have hydrolytic activity. Preliminary studies have demonstrated binding of pteroylmonoglutamate (folate) to membrane fractions that also cross-reacted with the PSM monoclonal antibody. We observed substantial carboxypeptidase activity as folate hydrolase associated with PSM antigen. The purpose of our study was to demonstrate that human prostatic carcinoma cells expressing PSM antigen exhibit folate hydrolase activity using methotrexate triglutamate (MTXGlu3) and pteroylpentaglutamate (PteGlu5) as substrates. Isolated membrane fractions from four human prostate cancer cell lines (LNCaP, PC-3, TSU-Prl, and Duke-145) were examined for folate hydrolase activity using capillary electrophoresis. After timed incubations at various pH ranges and in the presence and absence of thiol reagents, separation of pteroyl(glutamate)n derivatives was achieved with an electrolyte of sodium borate and SDS, while absorbance was monitored at 300 nm. The results demonstrate clearly that LNCaP cells, which highly express PSM, hydrolyze gamma-glutamyl linkages of MTXGlu3. The membrane-bound enzyme is an exopeptidase, because it progressively liberates glutamates from MTXGlu3 and PteGlu5 with accumulation of MTX and PteGlu1, respectively. The semipurified enzyme has a broad activity from pH 2.5 to 9.5 and exhibits activity maxima at pH 5 and 8. Enzymatic activity is maintained in the presence of reduced glutathione, homocysteine, and p-hydroxymercuribenzoate (0.05-0.5 mm) but was inhibited weakly by DTT (>/=0.2 mm). By contrast to LNCaP cell membranes, membranes isolated from other human prostate adenocarcinoma cells (PC-3, Duke-145, and TSU-Pr1) did not exhibit comparable hydrolase activity, nor did they react with 7E11-C5 monoclonal antibody. After transfection of PC-3 cells with a full-length 2.65-kb PSM cDNA subcloned into a pREP7 eukaryotic expression vector, non-PSM antigen-expressing PC-3 cells developed immunoreactivity to 7E11-C5 monoclonal antibody and demonstrated folate hydrolase activities and optimum pH activity profiles identical to those of LNCaP cells. The membrane-bound enzymes from both LNCaP- and PC-3-transfected cells also have a capacity to hydrolyze an alpha-linked glutamyl moiety from N-acetyl-alpha-aspartylglutamate. We have identified that PSM antigen is a pteroyl poly-gamma-glutamyl carboxypeptidase (folate hydrolase) and is expressed strongly in human prostate cancer. Cancer cells that express this enzyme are resistant to methotrexate therapy. Those developing future therapeutic strategies in the treatment of prostate cancer that utilize folate antagonists need to consider this mechanism of resistance.
 ...
PMID:Prostate-specific membrane antigen: a novel folate hydrolase in human prostatic carcinoma cells. 981 19

Chemotherapy with 5-FU and low-dose CDDP, MTX or LV has not been fully evaluated in urogenital tumors. In a study of advanced renal cell carcinoma, the response rate of the combination of 5-FU, CDDP and IFN-alpha was 9%. In urinary bladder cancer, the combination chemotherapy with 5-FU and low-dose CDDP has been used as a radiosensitizer. This combination chemotherapy with radiation introduced a high response rate and has been used for the preservation of bladder function with minimum invasive surgery. There are very few effective chemotherapies for advanced androgen independent prostate cancer. However, some oral fluoripyrimidine, like UFT, was shown to be effective to some extent for prostate cancer in a phase II study. Thus, combination therapies of 5-FU and low-dose CDDP for prostate cancer as a biochemical modulator may be expected.
 ...
PMID:[Combination chemotherapy with 5-FU and low-dose CDDP for urogenital tumors]. 1055 13

We reviewed the treatment results of urological cancer chemotherapy from the standpoint of evidence based medicine. In the treatment of advanced transitional cell carcinoma of the urothelium, M-VAC (MTX + VBL + ADM + CDDP) is regarded as the standard regimen; however, durable event-free survival is rare. There is no level 1 evidence to date showing that the use of neoadjuvant or adjuvant cisplatin-based regimens will improve survival in cases of locally advanced bladder cancer. Immunotherapy with interferon or interleukin-2 produces a small survival advantage in patients with metastatic renal cell carcinoma. There is no evidence that adjuvant interferon-alpha administration will improve the survival in those with non-metastatic renal cell carcinoma. Systematized cisplatin-based treatment protocols have been established in patients with advanced testicular germ cell tumor by means of many randomized controlled trials. Several clinical trials are under way to prove the efficacy of high dose chemotherapy (with autologous stem-cell support) in patients with poor risk germ cell tumors. We do not yet have sufficient data to conclude whether maximal androgen blockade will prolong the survival in patients with metastatic prostate cancer, nor to conclude whether neoadjuvant androgen depletion treatment improve disease free survival of the patients after radical prostatectomy.
 ...
PMID:[Evidence-based medicine for urological cancer chemotherapy]. 1070 Aug 88

A series of new aminopteroyl-based hydroxamate derivatives were synthesized and tested in vitro in cell culture models as potential dual target drugs. These compounds were designed to target two families of enzymes, matrix metalloproteinases (MMP) and a folate enzyme, dihydrofolate reductase (DHFR). These enzymes are the components of two unrelated cellular pathways and they are often over-expressed in metastasizing tumors. In addition to the synthesis and full structural characterization of the hybrid molecules, we describe their inhibitory activities against a series of MMPs (MMP-2, MMP-7, MMP-9, MMP-14) and DHFR, as well as their antiproliferative activity in three cancer cell lines. The new hydroxamate derivatives of MTX proved to be effective inhibitors of MMPs and DHFR in the micromolar and nanomolar range, respectively. Furthermore, they showed strong antiproliferative activity against A549 cells (non-small cell lung carcinoma), and PPC-1 and Tsu-Pr1 prostate cancer cell lines. Therefore, based on the present results, these bi-functional drugs may be good candidates to target specific tumors in animal models due to potential combined effects on two pathways crucial for tumor development.
 ...
PMID:Methotrexate gamma-hydroxamate derivatives as potential dual target antitumor drugs. 1712 67


1 2 Next >>