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)

Tumor-infiltrating lymphocytes (TIL) were isolated from 15 of 20 surgical specimens of transitional cell carcinoma of the urinary bladder, prostate cancer, testicular cancer, Wilms tumor and adrenal cancer. Expansion was carried out in four different culture conditions, each containing 1000 U/ml interleukin-2: RPMI medium with or without 20% (by volume) of lymphokine-activated killer cell (LAK) supernatant and AIM V medium with or without 20% LAK supernatant. The resultant cell populations were then assayed for cytotoxicity against a variety of autologous and allogeneic tumor targets and phenotypic analysis was performed with fluorescein-labeled monoclonal antibodies. TIL growth was unrelated to the initial percentage of lymphocytes or tumor cells present in the enzymatically dispersed specimens or whether fresh or cryopreserved tissue was utilized. Better growth was seen in AIM V than in RPMI medium (P = 0.013); the beneficial effect of the addition of LAK supernatant to RPMI was indicated (P = 0.065), and the addition of LAK supernatant to AIM V did not improve the ability to culture TIL (P = 0.5) from these cancers. TIL in long-term culture were predominantly CD3+. The ratio of CD4+/CD8+ cells varied with time in culture and culture medium, but most cultures eventually became CD4+. Cells bearing B cell, natural killer cell, and macrophage markers disappeared early in culture. Overall 14/15 TIL samples were lytic against one of the autologous and allogeneic targets tested, but specific lysis against the autologous tumor from which it was derived was seen in only one TIL culture originating from a bladder cancer. Our results suggest that TIL can be expanded to therapeutic levels from a variety of urological malignancies and that their potential role in future therapy should be further explored.
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PMID:Tumor-infiltrating lymphocytes from nonrenal urological malignancies. 210 45

Mice, homozygous for the mutation severe combined immunodeficiency (scid) and also segregating for the mutation hypogonadal (hpg), were tested for their potential use as an in vivo model system for studying the growth of human prostate cancer and benign hyperplastic prostate tissue grafts. Fresh human prostate cancer or benign hyperplastic prostate tissue was implanted subcutaneously into androgen-replete C.B. 17 scid/scid males, and into androgen-deficient hpg/hpg scid/scid or androgen-replete +/? scid scid males. The tissue grafts grew in both androgen-replete and androgen-deficient host mice. When dihydrotestosterone (DHT) was administered at tissue grafting, both the incidence and size of the tissue grafts increased. Histology of tissue from tumors in the androgen-deficient hpg/hpg scid/scid host showed either undifferentiated tumors or adenocarcinomas with few glandular structures. These data suggest the androgen deficient environment selected for growth of androgen-independent tumor tissue. Finally, when interleukin-2 (IL-2)-activated tumor-infiltrating lymphocytes were injected into scid/scid hosts, the cells were found to survive and could be identified in the spleen of the recipient mice. These results indicate that growth of human prostate tissues and IL-2-activated lymphocytes in scid/scid mice is a viable model system for in vivo studies of prostatic disease.
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PMID:Survival of human prostate carcinoma, benign hyperplastic prostate tissues, and IL-2-activated lymphocytes in scid mice. 754 29

The binding of several biotinylated biologic probes was determined in sections of 20 surgical specimens of prostate cancer and of 21 biopsy specimens of hyperplastic prostate. Whereas neither the immunomodulatory, galactoside-specific lectin from Viscum album nor the human beta-galactoside-specific lectin (M(r) 14 kd) or its specific antibody discerned any remarkable differences, the lectin from Urtica dioica (UDA) and interleukin-2, the in vitro production of which is enhanced by this lectin, exhibited obvious preference for hyperplastic cells. In addition, the presence of binding sites for chemically synthesized blood group determinants was tested. Carcinoma cases revealed a higher percentage of binding of synthetic blood group trisaccharide H than hyperplasia cases. Due to these differences, diverse parameters, derived from measurement of integrated optical density (IOD) and from syntactic structure analysis, were correlated with the extent of binding of these biologic probes for the tumor cases. Primarily, parameters that are related to computation of a minimum spanning tree were significantly different in positive and negative cases for both UDA and interleukin-2. For the binding of blood group trisaccharide H the 5C exceeding rate, the 2CV deviation index and the distance of neighboring tumor cells with an IOD > 5 were clearly dissimilar. Our results thus suggest an extension of the panel of biologic probes for prostate cancer and substantiate the usefulness of correlations of binding of selected biologic probes to features derived from the assessment of IOD and syntactic structure analysis.
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PMID:Expression of lectin, interleukin-2 and histopathologic blood group binding sites in prostate cancer and its correlation with integrated optical density and syntactic structure analysis. 754 1

Natural killer cytolytic activity, the basis of cancer immunotherapy that uses cytolytic cells, may be impaired in cancer. The aim of this work was to study in vitro the natural killer cytolytic activity and its response to the immunomodulators interleukin-2, interferon and phytohemagglutinin stimulated lymphocyte proliferation in a group of 9 patients with renal cell cancer and 6 with prostatic cancer. The results were compared with those of 20 normal volunteers. Twelve patients were operated and were studied twice 48 h and 14 days after surgery. Natural killer cytolytic activity was significantly lower in renal cell and prostatic cancer patients than controls (3.3 +/- 1.6, 4.9 +/- 2.2 and 20.6 +/- 3.7% of specific lysis respectively). This activity was not modified in cancer patients by interleukin-2 50 UI/ml or interferon 3000 UI/ml and did not differ in the two postoperative periods. Phytohemagglutinin stimulated lymphocyte proliferation was also lower in cancer patients, compared to controls (stimulation index of 18 +/- 3 and 26.5 +/- 5 respectively). It is concluded that these patients have a low immunological level and that this study is the first step towards an immunological characterization of cancer patients that are candidate to adoptive immunotherapy.
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PMID:[Natural killer cytolytic activity in renal and prostatic cancer]. 773 6

In order to establish a more effective and safer therapy for androgen-dependent prostate cancer, to be used in addition to hormonal therapy, the anti-tumor effects of intralesionally administered macrophages activated with recombinant interferon-gamma (INF-gamma), alone or in combination with recombinant interleukin-2 (IL-2) were studied in mouse prostate cancer models. Firstly, in terms of cellular adoptive immunotherapy, phagocytosis against Latex bead and cytotoxicity against Shionogi 115 cancer cell line (SC115) of macrophages activated with INF-gamma for 24 hour were investigated. One ml of 0.25% glycogen solution was intraperitoneally administered to male DS mice. Three days later, fluid was aspirated from the abdominal cavity and macrophages were separated for use in this experiment. Phagocytosis INF-gamma-dose-dependently increased and macrophages activated with 100 U/ml INF-gamma phagocytosed 78.3 +/- 4.5% (mean +/- SD) Latex bead. Cytotoxicity (modified MTT assay) of SC 115 by macrophages activated with 100 U/ml INF-gamma increased remarkably in comparison with non-activated macrophages and there was a significant increase in the effector-to-target-cell ratio to 40 in the activated group 77 +/- 4.3% (mean +/- SD) relative to 50 +/- 6.3% (mean +/- SD) in the non-activated group. Based on these in vitro findings, hormonal therapy and adoptive local immunotherapy, alone or together, were studied in mouse prostate cancer models. The prostate cancer model was prepared through the subcutaneous transplantation of SC115 in male DS mice and the treatments were initiated after tumors were palpable. The therapy protocols were as follows: Group I control and Group II received 20 mg/kg/day diethylstilbestrol diphosphate (DES-P) subcutaneously for 10 days, Group III received DES-P in combination with ten thousand units of IL-2 administered five times intralesionally, Group IV received DES-P in combination with 2 x 10(6) macrophages activated with 100 U/ml INF-gamma administered three times intralesionally, Group V received DES-P and IL-2 in combination with activated macrophages. The therapeutic efficiencies were evaluated by calculating the tumor volume and survival time. The results of the tumor volume on the 40th day post tumor transplantation were as follows (mean +/- SD): Group I 7,049 +/- 1,477 mm3, Group II 4,495 +/- 654 mm3, Group III 2,050 +/- 724 mm3, Group IV 2,782 +/- 970 mm3, Group V 1,555 +/- 514 mm3. The therapeutic groups showed significant tumor reduction relative to the control. Furthermore, intralesionally IL-2, the activated macrophages injected groups, alone or together, were more effective relative to the group receiving only DES-P.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Experimental study of the effects of hormonal therapy and intralesional injections of interleukin 2, activated macrophages on mouse prostate cancer models]. 808 32

In an effort to stimulate host-mediated antitumor response against prostate cancer in an animal model, highly malignant Dunning MAT-LyLu rat prostate carcinoma cells were transfected with the interleukin-2 (IL-2) cDNA, resulting in their ability to secrete large amounts of biologically active IL-2. Although parental cells form lethal tumors when injected subcutaneously into syngeneic hosts at doses of > or = 5,000, injections of IL-2 secreting cells initially formed tumors and regressed completely in each of over 200 animals at all doses tested (10(4)-8 x 10(7) cells). Mixtures of parental and IL-2 transfected cells were similarly rejected, demonstrating the non-cell autonomous nature of the response. Histological analysis of regressing tumors revealed a vigorous, predominantly lymphocytic and macrophage infiltrate at day 2 and marked tumor necrosis by day 6. Immunohistochemical staining of infiltrating lymphocytes at this latter time point demonstrated numerous T cells bearing either CD4 or CD8 surface markers, suggesting these cells as possibly mediating the tumor rejection. The ability of athymic mice to reject the IL-2 secreting tumor cells, however, suggests a non-T-cell-mediated mechanism. Although splenic natural killer (NK) activity is increased following injection of IL2 secreting tumor cells, this activity appears to be unnecessary for tumor elimination since syngeneic animals injected with asialo-GM1 antiserum to decrease NK activity also rejected IL-2 transfected cells, albeit slightly less effectively than untreated animals. Immunization of animals with subcutaneous injections of IL-2 transfected cells protected animals against a subsequent challenge of 10(4) wild-type cells 1 to 2 weeks later in 19 of 51 cases; however, immunization did not confer protection against larger doses of parental tumor. These studies indicate that high local concentrations of IL-2 stimulate the elimination of large local burdens of prostate cancer in this model system, and this elimination results in a weak, but detectable systemic immune response against wild-type prostate cancer cells.
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PMID:Interleukin-2 transfected prostate cancer cells generate a local antitumor effect in vivo. 817 Aug 37

Prostate cancer is one of the leading causes of cancer deaths in the Western world and current therapies are of limited efficacy in advanced disease. Both ex vivo and in vivo gene therapy strategies offer exciting new possible approaches to the management of this disease. Ex vivo gene therapy involving interleukin-2 or granulocyte-macrophage colony-stimulating factor transduced whole tumour cell vaccines has shown great promise in animal models. The feasibility of in vivo corrective gene therapy involving the replacement of mutant tumour suppressor genes, antisense strategies and the insertion of suicide genes has been demonstrated in preclinical models. Several of these therapies are now entering phase I/II studies in patients with prostate cancer.
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PMID:Gene therapy for prostate cancer. 890 97

The purpose of this study was to determine the effectiveness and toxicity of local continuous immunotherapy of prostatic cancer. A group of 60 young male Copenhagen rats with Dunning adenocarcinoma of the prostate, implanted subcutaneously into both flanks, after proven tumor growth, were treated with either human interleukin-2 (IL-2) depot preparations (n = 30) or albumin (placebo) depot preparations (n = 30) implanted directly into one tumor site. IL-2 depots released IL-2 reliably for more than 24 days. The rat serum was tested during treatment for human IL-2, possibly absorbed from depots, and for rat interferon gamma. IL-2 treatment reduced tumor growth significantly (P < 0.001) compared with albumin-treated sites or untreated contralateral sites. No toxicity was observed during treatment. Neither human IL-2 nor rat interferon gamma was detected in the serum, which indicates an exclusively local IL-2 effect. IL-2 depot preparations reduce tumor growth in Dunning adenocarcinoma of the prostate significantly without toxicity.
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PMID:Intratumoral depot interleukin-2 therapy inhibits tumor growth in Dunning adenocarcinoma of the prostate implanted subcutaneously in rats. 962 Feb 19

Prostate cancer is one of the leading causes of cancer deaths in the western hemisphere. A number of different gene therapy strategies are currently being evaluated. The ex vivo and many of the in vivo therapies involve stimulating a specific antitumor immune response. Autologous vaccines involving interleukin-2 (IL-2)- or granulocyte-macrophage colony-stimulating factor (GM-CSF)-transduced whole tumor cells showed great promise in animal models. Clinical trials of these and other vaccine strategies are underway. In vivo gene therapies involving the replacement of mutant tumor-suppressor genes, antisense strategies, and the insertion of suicide genes are also being evaluated in prostate cancer.
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PMID:Gene therapy for prostate cancer. 1048 88

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.
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PMID:[Evidence-based medicine for urological cancer chemotherapy]. 1070 Aug 88


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