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

Adenocarcinoma of the prostate is one of the most common malignant tumors in adult males. Hormonal therapy is the treatment of choice for patients with systemic disease concerning 80% response rate. Androgen ablation is now the first hormonal manipulation and can be achieved either by means of bilateral orchiectomy or of LH-HR agonist therapy: both are equally effective. Total androgen blockage (association between orchiectomy or LH-RH agonist and non-steroidal anti-androgens) would be reserved for controlled clinical trials only. Estrogens had the same efficacy, but revealed the serious cardio-vascular events. Endocrine therapy does not prolong survival but provides good palliation. Palliation should be given when there is something to palliate. Prostate cancer is usually not recognized as being sensitive to cytotoxic agents. Single agent or combination chemotherapy has not been shown to have a role as first line treatment of disseminated disease and is usually used for hormone refractory disseminated disease.
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PMID:[The hormonal and chemotherapy of prostatic cancer]. 945 33

Radiotherapy is an effective treatment for localized prostate cancer. A dose response relationship has been demonstrated for both local tumor control and complications. Reducing the volume of normal tissue treated may allow dose escalation without an increase in RT induced side effects. Androgen blockade before RT could, by reducing tumor volume, increase local control, disease-free (DFS) and overall survival in patients (pts) with prostatic adenocarcinoma. A total of 79 patients with T2-T4 prostate cancer have been treated initially with LHRH agonists and cyproterone acetate followed by radical irradiation between 1988 and 1993. The first cohort of 22 patients were monitored intensively by transrectal ultrasound and computed tomography. For each patient conformal photon beam radiotherapy and conventional treatment plans were produced and dose volume histograms compared for total volume, rectal volume, and bladder volume. Overall mean reduction of prostate volume was about 50%, and radiotherapy target volume was reduced by 37%. 53 further patients without clinical evidence of regional or distant metastases were given 3 months preradiotherapeutic hormonal cytoreduction with a short course of cyproterone acetate and LHRH. PSA level fell rapidly in most patients and after 3 months treatment the median PSA level was 1 ng/ml and 83% had PSA level 10 ng/ml. At 18 months PSA levels continued to be < 2 ng/ml in 70% of the patients. Combined modality treatment with the neoadjuvant or adjuvant androgen deprivation and conformal therapy show considerable promise as novel methods to improve the therapeutic ratio. This treatment approach may be used to explore the possibility of dose escalation in prostate cancer to enhance local control, and therapeutic randomised studies are underway to test these approaches.
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PMID:[Basic principles and initial results of adjuvant hormone therapy and irradiation of prostatic carcinoma]. 948 May 9

Androgen withdrawal is a major therapeutic modality in the treatment of prostate cancer. Although tumors initially respond, they subsequently relapse, and these recurring tumors are androgen independent. To examine possible mechanisms to explain the androgen independence of prostate cancer, we have expressed cytokine response modifier A (CrmA), a competitive inhibitor of caspases, interleukin 1beta-converting enzyme-like proteases, which mediate apoptotic cell death, in the human androgen-dependent prostate cancer cell line LNCaP. LNCaP cells require androgens for continuous growth in culture and to form tumors in nude mice. The expression of CrmA in LNCaP cells prevented the decreased growth rate induced by androgen withdrawal in tissue culture. When CrmA-expressing LNCaP (LNCaP-CrmA) cells were implanted s.c. in nude mice, the tumors grew six times faster than parental cells. Androgen ablation by castration before tumor implantation suppressed the ability of control LNCaP cells expressing nonfunctional CrmA mutant (R291T) to form tumors, but LNCaP-CrmA cells formed tumors similar in size to those formed in normal mice. When orchiectomy was performed 10 days after tumor implantation, control LNCaP cells expressing a nonfunctional CrmA mutant (R291T) regressed, but LNCaP-CrmA tumors continued to grow. Thus, inhibition of caspases prevents androgen withdrawal-induced prostate cancer cell death, suggesting that caspase activation is normally an important part of this process.
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PMID:Inhibition of caspases by cytokine response modifier A blocks androgen ablation-mediated prostate cancer cell death in vivo. 948 43

Androgen plays a critical role in regulating the growth and differentiation of normal prostate epithelia, as well as the initial growth of prostate cancer cells. Nevertheless, prostate carcinomas eventually become androgen-unresponsive, and the cancer is refractory to hormonal therapy. To gain insight into the mechanism involved in this hormone-refractory phenomenon, we have examined the potential role of the androgen receptor (AR) in that process. We have investigated the expression of AR and two prostate-specific androgen-responsive antigens, prostatic acid phosphatase (PAcP) and prostate-specific antigen (PSA), for the functional activity of AR in LNCaP and PC-3 human prostate carcinoma cells. Our results are as follows. (i) Clone 33 LNCaP cells express AR, PAcP, and PSA, and cell growth is stimulated by 5alpha-dihydrotestosterone (DHT). Stimulation of cell growth correlates with decreased cellular PAcP activity. (ii) In clone 81 LNCaP cells, the expression of PAcP decreases with a concurrent decrease in the degree of androgen stimulation of cell growth, whereas the expression of PSA mRNA level is up-regulated by DHT, as in clone 33 cells. Conversely, in PAcP cDNA-transfected clone 81 cells, an additional expression of cellular PAcP correlates with an increased stimulation by androgen, higher than the corresponding control cells. (iii) PC-3 cells express a low level of functional AR with no detectable PAcP or PSA, and the growth of PC-3 cells is not affected by DHT treatment. Nevertheless, in two PAcP cDNA-transfected PC-3 sublines, the expression of exogenous cellular PAcP correlates with androgen stimulation. This androgen stimulation of cell growth concurs with an increased tyrosine phosphorylation of a phosphoprotein of 185 kDa. In summary, the data indicate that the expression of AR alone is not sufficient for androgen stimulation of cell growth. Furthermore, in AR-expressing prostate cancer cells, the expression of cellular PAcP correlates with androgen stimulation of cell proliferation.
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PMID:Expression of human prostatic acid phosphatase correlates with androgen-stimulated cell proliferation in prostate cancer cell lines. 948 33

Androgen-dependent prostate cancer cells eventually progress to androgen -independent cells after hormonal manipulation. Due to chemotherapeutic drug resistance and toxic side effects, new targets for antineoplastic therapy are urgently needed. In the present study, cerulenin, a fatty acid synthase inhibitor, was used to induce the death of androgen-independent prostate cancer cells. Cerulenin induces the apoptosis of TSU-prl cells based upon the temporal sequence of DNA fragmentation, morphologic changes and loss of cell viability. During apoptotic process induced by the agents, expression of cyclin-dependent kinase inhibitors p21 and p27 increased, whereas expression of cyclin D1 decreased. Flow cytometric analysis showed that the treatment resulted in a block in G2/M of the cell cycle. These results demonstrated that inhibition of fatty acid synthesis could be a target to treat hormone-independent prostate cancer cells via apoptosis, and cyclin-dependent kinase inhibitors played some role during apoptotic pathway.
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PMID:Apoptosis of androgen-independent prostate cell line induced by inhibition of fatty acid synthesis. 949 73

Urological malignancies kill over 16,000 people annually in England and Wales. There have been exciting recent developments in our understanding of the molecular pathogenesis of these diseases, although many questions remain unanswered. Three separate genes (WT1, WT2, and WT3) have been implicated in Wilms' tumour development. Patients with von Hippel-Lindau (VHL) syndrome develop renal cell carcinoma and it has been shown that VHL protein inhibits elongin, a cellular transcription factor which controls RNA elongation. Use of molecular markers to identify superficial bladder tumours likely to progress to muscle invasive disease has met with some success. Increased epidermal growth factor receptor (EGFR) and p53 expression, and decreased E-cadherin expression all correlate with tumour progression. Tumours in patients with carcinoma in situ have distinct molecular features. Androgen ablation delays disease progression in men with prostate cancer, but relapse is inevitable. Research has been directed towards elucidating the mechanisms by which prostate cancer 'escapes' hormonal control. Mutations in the androgen receptor have been identified. It is apparent that locally produced growth factors mediate androgen-dependent processes and these too have been implicated in prostate carcinogenesis.
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PMID:The molecular pathology of urological malignancies. 949 53

We report an unusual case of prostatic carcinomatous meningitis and remind clinicians to maintain a high index of suspicion of meningeal involvement when patients with advanced prostatic cancer present with cerebral symptoms, back pain, or neurologic findings. The diagnosis may require repeated cytologic examinations of cerebrospinal fluid, and immunocytochemical stains should be considered to confirm a prostatic source if malignant cells are identified. Androgen ablative therapy may give prolonged remissions, especially in patients with previously untreated tumours.
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PMID:Prostatic meningeal carcinomatosis presenting as delirium tremens. 949 52

Androgen independent prostate cancer is recognized as a chemotherapy resistant disease. Human prostate carcinoma DU-145, LNCaP and PC-3 cells in monolayer in exponential growth were exposed to various concentrations of melphalan, 4-hydroperoxycyclophosphamide or adriamycin for 1 hour. These cells were all responsive to the drugs, with DU-145 cells being the least sensitive and PC-3 cells the most sensitive. When the three human prostate carcinoma cell lines were grown as xenografts in nude or SCID mice and the animals treated with single doses of melphalan, cyclophosphamide or adriamycin, the tumors were not very responsive to the drugs. The DU-145 tumors were highly resistant to each drug. The PC-3 tumors were more sensitive; however, even the PC-3 tumors were less drug responsive than several murine tumors. All three prostate cell lines secreted transforming growth factor-beta (TGF-beta) into the cell culture medium, and when grown as xenograft tumors increased the plasma levels of TGF-beta in the animals. DU-145 cells produced the most TGF-beta and LNCaP cells produced the least. After administration of single doses of each of the chemotherapeutic agents to animals bearing the prostate carcinoma xenografts, there was a time dependent increase in plasma TGF-beta that was greatest in animals bearing the DU-145 tumor and least in animals bearing the LNCaP tumor. Immunohistochemical staining, showed that PC-3 tumors tended to have the most intense staining for TGF-beta and LNCaP tumors the least. In situ hybridization for TGF-beta mRNA showed an increase in TGF-beta mRNA that was time independent after chemotherapy administration in all three tumors. These results support the hypothesis that the drug resistance of prostate carcinoma is manifest in vivo, and that in vivo high levels of TGF-beta may protect these tumors from cytotoxic cancer therapies.
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PMID:Prostate carcinoma response to cytotoxic therapy: in vivo resistance. 950 95

Androgen receptors are present in both pancreatic cancer tissue and cell lines. Flutamide is a potent antiandrogen widely used in clinical practice for patients with metastatic prostate cancer. This Phase II trial was undertaken to evaluate the impact of flutamide in patients with advanced pancreatic adenocarcinoma who had developed progressive disease following therapy with one 5-FU-based regimen. Fourteen patients were treated with flutamide, 250 mg orally three times per day. Therapy was generally well tolerated. No patients achieved objective tumor response. No patient had improvement in tumor-related symptoms as measured by improvement in pain intensity, analgesic requirement, performance status, or nutritional status. Median survival was 4.7 months. We conclude that flutamide is ineffective second line therapy for patients with advanced pancreatic adenocarcinoma.
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PMID:Phase II study of flutamide as second line chemotherapy in patients with advanced pancreatic cancer. 954 80

Fibroblast growth factor (FGF) 8, also known as androgen-induced growth factor, was originally isolated from an androgen-dependent mouse mammary Shionogi carcinoma SC-3 cell line, in which it was shown to have androgen-regulated properties. We previously demonstrated that Fgf 8 transcripts were detected in several human prostate and breast cancer cell lines and that recombinant FGF 8 was mitogenic to an androgen-sensitive prostate cancer LNCaP cell line. In this study, to characterize the roles of FGF 8 in clinical hormone-responsive cancers, we established a monoclonal antibody against FGF 8. In Western blots, this antibody specifically interacted with a FGF 8b isoform that was identical between mouse and human but was not identical to other murine 8a and 8c isoforms. In a cell growth assay using SC-3 cells, the newly established anti-FGF 8 antibody blocked androgen- and FGF 8-stimulated growth but not basic FGF-stimulated growth. Immunohistochemical analyses by use of the established anti-FGF 8 antibody demonstrated that FGF 8 was frequently expressed in human prostate cancers, appearing in 40 of 43 cases (93%), whereas both prostatic hyperplasia specimens and normal prostate tissues included in biopsy specimens were negative for FGF 8 expression. On the other hand, FGF 8 was detected in normal ductal and lobular epithelial cells in breast tissues. FGF 8 was also frequently expressed in various breast diseases, including fibroadenomas (5 of 5 cases, 100%), intraductal papillomas (3 of 3 cases, 100%), ductal hyperplasias (3 of 6 cases, 50%), and breast cancers (8 of 12 cases, 67%). Androgen receptors were also immunohistochemically detected in FGF 8-positive prostate cancers (40 of 40 cases, 100%) and FGF 8-positive breast diseases (17 of 19 cases, 89%). These findings strongly suggest that FGF 8 is involved in hormone-related tumorigenesis of the prostate and breast.
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PMID:High frequency of fibroblast growth factor (FGF) 8 expression in clinical prostate cancers and breast tissues, immunohistochemically demonstrated by a newly established neutralizing monoclonal antibody against FGF 8. 960 40


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