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)

To determine the efficacy of recombinant human leukocyte alpha-interferon (IFL-RA) in advanced hormone-refractory prostate cancer, the authors treated 40 patients with IFL-RA administered intramuscularly at a dose of 10 x 10(6) U/m2 three times weekly. Toxicity was substantial and necessitated at least a 50% dose reduction in all but five patients during the first 1-2 months of therapy. No responses were observed in patients with bone metastases, but complete and partial regression of nodal disease were observed in two patients with extraosseous disease (overall response rate, 5%; 95% confidence interval, 0.64-17.75%). The authors conclude that IFL-RA cannot be recommended at this dose and schedule in patients with advanced prostate cancer, but additional study of its use in patients with nodal disease may be warranted.
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PMID:A phase II study of recombinant human alpha-interferon in advanced hormone-refractory prostate cancer. 138 29

The effect of interferon beta ser (IFN beta ser) on the growth of three prostatic cancer cell lines DU-145, PC-3 and LNCaP was studied. IFN beta ser inhibited growth of anchorage dependent semiconfluent monolayers and anchorage dependent colony formation of both DU-145 and PC-3 in a dose dependent manner but had no effect on LNCaP. Transforming growth factor beta (TGF beta 1) inhibited proliferation of DU-145 and PC-3 cells in 1% but not 8% fetal calf serum. The combination of TGF beta 1 and IFN beta ser was additive in its effects on growth. Neither epidermal growth factor (EGF) nor transforming growth factor alpha (TGF alpha) reduced the antiproliferative effect of IFN beta ser on these cells. These antiproliferative effects were reproduced in studies on primary epithelial cell cultures derived from prostate specimens with various pathologies. The potential use of IFN beta ser in combination with hormonal therapy to delay the development of hormone refractory tumors is discussed.
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PMID:Effects of interferon beta ser and transforming growth factor beta on prostatic cell lines. 189 45

Any attempt to eradicate the heterogeneous cell population of a tumour mass would require the use of appropriate combination treatment protocols. The antitumour effects of interferon alpha (IFN alpha) in combination with AS2-1, the hydrolysis product of 3-phenylacetyl-amino-2,6-piperidinedione, were examined using several human tumour cell lines as a model. These included the malignant melanoma A375, adenocarcinoma of the prostate PC3 (hormone-insensitive bone metastasis), and the erythroleukaemia line K562. AS2-1 suppressed tumour growth through non-toxic mechanisms, with 1 mg/ml causing approximately 50% inhibition of the melanoma and prostate tumour cell proliferation. By contrast, primary normal human skin fibroblasts were significantly less sensitive to the antiproliferative effect of AS2-1. Suppression of tumour growth was seen also with AS2-1 treatment of the erythroleukaemia K562; in these cultures the drug also induced dose-dependent differentiation, as indicated by the increased haemoglobin production. Interestingly, addition of low doses of IFN alpha markedly enhanced the antitumour and differentiating effects observed with AS2-1. Treatment with 200-300 IU/ml of IFN (which caused about 20% inhibition of growth) together with 1 mg/ml of AS2-1 resulted in over 80% inhibition of the melanoma and prostate cancer cell proliferation, suggesting a synergistic activity of the two agents. This was substantiated by quantitative analysis of the differentiation induced in K562 erythroleukaemia. It appears, therefore, that IFN alpha and AS2-1 may act through synergistic mechanisms to effectively inhibit tumour growth and promote differentiation in a variety of human malignant cell lines.
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PMID:Interferon in combination with antitumourigenic phenyl derivatives: potentiation of IFN alpha activity in-vitro. 193 16

Interferon-alpha (IFN-alpha) producing capacity was measured in 47 patients with prostatic cancer by whole blood assay. The mean IFN-alpha producing capacity of prostatic cancer patients was 3657 IU/ml, which indicated a significantly (p less than 0.005) lower value than that in healthy male aged 50 years or more. IFN-alpha producing capacity in patients with Stage D disease was lower than that with Stage A, B or C. The higher the grade of the disease, the lower tended to be the capacity. A certain relationship was suspected between IFN-alpha producing capacity and the prognosis of each patient. In particular, in patients with prostatic cancer in Stage D, the prognosis was worse in low IFN-alpha producing capacity group (less than 3000 IU/ml) than in normal or high IFN-alpha producing capacity group (greater than or equal to 3000 IU/ml). It was considered that IFN-alpha producing capacity might be useful in developing the prognosis of patients with prostatic cancer.
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PMID:[Interferon-alpha producing capacities in prostatic cancer patients]. 232 24

The effect of purified human fibroblast beta-interferon (B-IFN) and recombinant alpha-2b-interferon (A-IFN) on cell proliferation was investigated in two human prostate carcinoma cell lines, named PC-3 and DU-145. Both cell lines respond to the antiproliferative action of interferon, B-IFN being more effective than A-IFN. PC-3 is more sensitive than DU-145 cell line, showing 95% inhibition of cell proliferation at the highest concentration of B-IFN. As interferons, besides reducing cell growth, are able to modify steroid receptor content in different hormone-sensitive human tumours, our results may be of some relevance as these drugs might be used to regulate both cell proliferation and hormone-sensitivity in prostate cancer.
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PMID:Antiproliferative effect of interferons on human prostate carcinoma cell lines. 273 78

Experiments were performed to ascertain whether or not the cytotoxic effects of various anticancer drugs on five human genitourinary malignant cell lines would be enhanced by recombinant gamma-type interferon. The cells used were as follows: HeLa cells from a uterine cervix cancer, HT-1376 and EJ cells from bladder cancers, ACHN cells from a renal cancer, and PC-3 cells from a prostatic cancer. The effects of the drugs were studied by colony formation assay. The following drugs were used: two metabolic antagonists. cytosine arabinoside (Ara-C) and 5-fluorouracil (5-FU), three antibiotics: adriamycin (ADM), mitomycin C (MMC) and peplomycin (PEP), two alkylating agents: nimustine hydrochloride (ACNU) and melphalan, one vinca alkaloid: vincristine (VCR) and one other drug: cisplatin (CDDP). Interferon used was a preparation of recombinant gamma-type interferon. PEP showed synergistically enhanced cytotoxic effects on HeLa, EJ, HT-1376, and ACHN cells by concomitant application with gamma-IFN. Synergistic cytotoxicity was also detected against HeLa, EJ and ACHN by combined treatment with ADM and gamma-IFN. A similar enhanced cytotoxicity was demonstrated in HT-1376 and PC-3 by 5-FU treatment with gamma-IFN. MMC showed enhanced cytotoxicity only against ACHN cells in the presence of gamma-IFN. The cytotoxic effects of PEP on cells were increased by lower concentrations of gamma-IFN compared with those of other drugs. DNA, RNA and protein synthesis were examined in HeLa cells following combined exposure to PEP and gamma-IFN. The combined therapy was found to produce a specific decrease in DNA synthesis, while yielding no significant inhibition of intracellular RNA and protein synthesis.
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PMID:[Potentiation of the cytotoxic effects of anticancer drugs on human genitourinary neoplastic cells by recombinant gamma-interferon]. 310 39

Suramin has shown antitumour activity in vitro and in vivo. At plasma levels higher than 200 microM there is, however, excessive toxicity. We have, therefore, attempted to improve the antitumour effects of suramin in vitro by combining it with several other antitumour agents. The MCF-7 mammary carcinoma and PC3 prostate cancer cell lines were exposed continuously to suramin and the other agents for 6 days. The sulphorhodamine B (SRB) assay was used for the assessment of growth inhibition. The dose-response interactions were evaluated using the median-effect analysis with the Chou and Talalay computer programme. In the MCF-7 cell line, the combination of suramin plus doxorubicin (DXR), cisplatin (CDDP), 5-fluorouracil (5-FU) or tumour necrosis factor (TNF) resulted in synergistic growth inhibition, whilst its combination with miltefosine (HPC) was antagonistic. In the PC-3 cell line, suramin plus CDDP or TNF was synergistic, whilst its combination with DXR, 5-FU and HPC was antagonistic. All tested combinations with interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma) and with the combination of both IFN-alpha+IFN-gamma were not synergistic. The synergistic effect of suramin with DXR was schedule dependent. Pretreatment (addition of DXR on day 1 and suramin on days 2-5) was additive at the IC50 level, in both cell lines. Addition of DXR at day 5 was more effective than simultaneous exposure. We found a synergistic effect for the combination of suramin with CDDP and TNF in both cell lines. In addition the combination with DXR and 5-FU was synergistic in MCF-7. Sequential administration of DXR-suramin or suramin-DXR increased the growth inhibition.
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PMID:The synergistic and antagonistic effects of cytotoxic and biological agents on the in vitro antitumour effects of suramin. 783 16

Immunotherapy with subcutaneous rIL-2 and alpha IFN was administered to stage D3 prostate cancer patients after failure of secondary treatment with oral estramustine phosphate. Of a total of 15 patients, 2 are in partial response, with estramustine maintained after 44+ and 36+ weeks, respectively. Response to estramustine was observed initially in 7 of 13 patients, with a median duration of 12 weeks (range 8-20). No response to estramustine was observed in the remaining 6 patients. After the failure of estramustine, 13 patients were treated with immunotherapy. After the first cycle, progression of disease no therapy was given to those patients. A reduction of PSA levels was observed during the first cycle in 2 patients (15.3%); levels subsequently increased during the second cycle of treatment. A partial response was observed in 4 patients (30.7%), with a reduction of PSA levels in 3. The duration of response was 28 and 32 weeks in 2 patients who survived after failure for 18 and 21 weeks, respectively. Two patients are still alive, with continued partial response at 62+ and 42+ weeks. Side effects were represented mainly by a flu-like syndrome, associated with fever and nausea in all patients. The serum concentration of IL-10 was measured in 8 patients under study and in 11 matched controls. Levels higher than mean + 2D of controls before, during, or after immunotherapy were correlated with treatment failure, whereas levels below 6 ng/ml were encountered among the patients who showed a clinical response and a reduction of PSA during treatment. Within the limitations of this pilot study, it appears difficult to distinguish between a spontaneously slowly progressing disease and a true response to therapy.
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PMID:Salvage immunotherapy with subcutaneous recombinant interleukin 2 (rIL-2) and alpha-interferon (A-IFN) for stage D3 prostate carcinoma failing second-line hormonal treatment. 861 53

Prostate cancer, like other types of cancer, is associated with the loss of cell cycle control, resulting in unregulated growth of cells. We report here on the inhibitory effects of interferon alpha (IFN alpha) on the cell cycle of prostate cancer cells, using the human prostate carcinoma cell line DU145 that has mutations in the tumor suppressor genes pRB, p53 and KAI1. IFN alpha inhibited growth and colony formation of DU145 cells and analysis by flow cytometry suggests that IFN alpha inhibited the progression of these cancer cells from the G1 through S phase of the cell cycle. IFN alpha treatment of DU145 cells reduced cyclin dependent kinase 2 (cdk2) activity. In particular, cyclin E dependent cdk2 activity was inhibited by IFN alpha treatment. IFN alpha treatment, however, did not affect the amount of cdk2 bound to cyclin E. Consistent with this data, IFN alpha was able to induce expression of the kinase inhibitor p21 in DU145 cells. Furthermore, IFN treatment increased the amounts of p21 complexed with cdk2 in these cells. These data support a role for p21 in mediating the antiproliferative action of IFN alpha. The induction of p21 and its growth inhibitory effects in DU145 cells appears independent of p53, pRB and KAI1 status.
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PMID:IFNalpha induces the expression of the cyclin-dependent kinase inhibitor p21 in human prostate cancer cells. 912 65

The class I IgG receptor (Fc gamma RI or CD64 receptor), which is present on key cytotoxic effector cells, has been shown to initiate the destruction of tumor cells in vitro and has been hypothesized to play a role in the destruction of antibody-coated cells such as platelets in idiopathic thrombocytopenia purpura (ITP). This overview summarizes the clinical experience with CD64-directed immunotherapy in cancer patients with the bispecific antibodies MDX-447 [humanized Fab anti-CD64 x humanized Fab anti-(epidermal growth factor receptor, EGFR)] and MDX-H210 (humanized Fab anti-DC64 x Fab anti-HER2/neu), and with the anti-CD64 monoclonal antibody (mAB) MDX-33 (H22) in the modulation of monocyte CD64 in vivo. In an ongoing phase I/II open-label trial with progressive dose escalation (1-15 mg/m2), patients with treatment refractory EGFR-positive cancers (renal cell carcinoma (RCC), head and neck, bladder, ovarian, prostate cancer and skin cancer) are treated weekly with intravenous MDX-447, with and without granulocyte-colony-stimulating factor (G-CSF). MDX-447 has been found to be immunologically active at all doses, binding to circulating monocytes and neutrophils (when given with G-CSF), causing monocytopenia and stimulating increases in circulating plasma cytokines. MDX-447 is well tolerated, the primary toxicities being fever, chills, blood pressure lability, and pain/ myalgias. Of 36 patients evaluable for response, 9 have experienced stable disease of 3-6 month's duration. The optimal dose and the maximal tolerated dose (MTD) have yet to be defined; dose escalation continues to define better the dose, toxicity, and the potential therapeutic role of this bispecific antibody. Three MDX-H210 phase II trials are currently in progress, all using the intravenous dose of 15 mg/m2 given with granulocyte/macrophage (GM-CSF). These consist of one trial each in the treatment of RCC patients, patients with prostate cancer, and colorectal cancer patients, all of whom have failed standard therapy. At the time of writing, 11 patients have been treated in these phase II trials. Four patients have demonstrated antitumor effects. Patients demonstrating responses include 2 with RCC and 2 with prostate cancer. One RCC patient has had a 54% reduction in size of a hepatic metastatic lesion and the other has had a 49% decrease in the size of a lung metastasis with simultaneous clearing of other non-measurable lung lesions. Regarding the two patients with prostate cancer, one has had a 90% reduction in serum prostate-specific antigen (PSA; 118-11 ng/ml), which has persisted for several months; the other patient with prostate has had a 70% reduction of serum PSA (872 ng/ml to 208 ng/ml) within the first month of treatment. Both patients have also demonstrated symptomatic improvement. In a completed phase I and in ongoing phase I/II clinical trials, patients with treatment-refractory HER2/neu positive cancers (breast, ovarian, colorectal, prostate) have been treated with MDX-H210, which has been given alone and in conjunction with G-CSF, GM-CSF, and interferon gamma (IFN gamma). These trials have been open-label, progressive dose-escalation (0.35-135 mg/m2) studies in which single, and more often, multiple weekly doses have been administered. MDX-H210 has been well tolerated, with untoward effects being primarily mild-to-moderate flu-like symptoms. The MTD has not yet been defined. MDX-H210 is immunologically active, binding to circulating monocytes, causing monocytopenia, as well as stimulating increases in plasma cytokine levels. Furthermore, some patients have evidence of active antitumor immunity following treatment with MDX-210. Antitumor effects have been seen in response to MDX-H210 administration; these include 1 partial, 2 minor, and 1 mixed tumor response; 15 protocol-defined stable disease responses have occurred. (ABSTRACT TRUNCATED)
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PMID:Clinical experience with CD64-directed immunotherapy. An overview. 943 76


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