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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The tumorigenicity, migration, growth and invasiveness of certain tumor cells is stimulated by basement membranes. Here we have examined the effect of Matrigel, an extract of basement membrane proteins, on the behavior of several prostate cancer cell lines, testing their growth and invasiveness in vitro and in vivo. Cells of the Tsu-prI line were more invasive than PC-3, Du-145, or LNCaP cells. Peptide inhibitors implicated laminin in the migration and invasion of these cells. When these cells were suspended in Matrigel and injected into nude mice, their growth was greatly enhanced, since large tumors formed in athymic nude mice whereas virtually no tumors were observed in the absence of Matrigel. The growth of a slowly growing line, LNCaP, was increased by exogenous basic fibroblast growth factor when injected with Matrigel. A laminin cell adhesion peptide, YIGSR, was a potent inhibitor of Matrigel-stimulated tumor growth implicating cell-laminin interactions in this process. These results suggest that tumor growth of prostate adenocarcinoma cells may be dependent both on cellular growth factors and on cell-matrix interactions mediated by laminin which facilitate the development of transplanted tumors in nude mice.
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PMID:Stimulation of human prostatic carcinoma tumor growth in athymic mice and control of migration in culture by extracellular matrix. 156 98

Copenhagen x Fisher F1 rats were implanted with the androgen-dependent Dunning R3327 prostatic adenocarcinoma. When the tumors had median volumes of ca 470 mm3, the rats were castrated and/or treated with 6-methylene-4-pregnene-3,20-dione (6MP) in different doses. Tumor growth inhibition occurred in all castrated and treated groups, with decrease in volume of the epithelial compartment in the intact group. Tumor volumes at the highest dose level of 6MP equalled those observed in the castrate group. Plasma levels of testosterone were within the normal range. The administration of 6MP surprisingly induced an increment of tumor blood flow in the castrate group. Also in castrated and testosterone-supplemented animals, 6MP induced a reduction of prostatic tumor growth. Through the castration-like effect on tumor growth, the use of 6MP may represent an attractive alternative to castration for treatment of androgen-responsive prostate cancer.
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PMID:Effects of 6-methylene progesterone on growth, morphology, and blood flow of the Dunning R3327 prostatic adenocarcinoma. 157 66

Researchers at the National Institute of Immunology (NII) in New Delhi, India have studied 2 vaccines to control fertility: the human chorionic gonadotropin (hCG) vaccine and the gonadotropin releasing hormone (GnRH) vaccine. Animal studies of both vaccines do not indicate any side effects. These 2 vaccines are at the clinical trial stage. Phase II clinical trials of hCG vaccine uses the heterospecies dimer conjugated to tetanus toxoid, diphtheria toxoid, or cholera toxin chain B as carriers. The subjects include hyperfertile women with at least 2 living children. They receive 3 primary immunizations every 6 weeks then a booster immunization as needed. As of May 1991, women with titers of 50ng of hCG bioneutralization capacity/ml had experienced 179 pregnancy-free cycles, and their sexual activity surpasses that prior to receiving the vaccine. 1 study shows that the lung tumors in nude mice which have passive immunization with anti-alpha hCG antibodies necrotize when researchers implant lung tumor cells. Injection of antibodies at the same time of implantation of tumor cells inhibits lung tumor growth. NII researchers plan to conduct a clinical trial with a beta hCG vaccine conjugated with vaccinia in lung cancer patients. The GnRH vaccine has the potential to be effective in both men and women. A study in male rats using diphtheria toxoid as the GnRH vaccine carrier reveals that antibody titers rise, testosterone levels fall, weight of testis decreases, and the prostate disappears. NII has begun clinical trials with postpartum women and, as of April 1992, 20 women were enrolled and immunized at 2 centers in India. Similar research in monkeys does not show evidence of passage of GnRH antibodies through breast milk. GnRH vaccine research in prostate cancer patients demonstrates declining levels of testosterone, luteinizing hormone, and follicle stimulating hormone, shrinkage of the prostate, and clearance of urinary ducts.
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PMID:Vaccines for control of fertility and hormone dependent cancers. 161 3

The response of two androgen-responsive rat prostatic cancers (i.e., Dunning R-3327 H and G sublines) and one androgen-responsive human prostatic cancer (i.e., PC-82) to the 5 alpha-reductase inhibitor, SK&F 105657, was tested in vivo. SK&F 105657 was administered orally twice a day at a dose of 25 or 50 mg/kg/dose. The rat R-3327 G tumor and the human PC-82 tumor have a low to undetectable level of tissue 5 alpha-reductase activity and both responded to SK&F 105657 treatment with a reproducible inhibition of tumor growth. Associated with this antitumor effect was a major decrease (i.e., greater than 70%) in tissue dihydrotestosterone (DHT) content in both tumors. By contrast, the rat R-3327 H prostatic cancer has a much higher level of tissue 5 alpha-reductase activity, and neither tumor DHT content nor growth of the tumor was inhibited by treatment with SK&F 105657. Drug treatment of rats bearing R-3227 H tumors resulted in a similar reduction in the DHT content, wet weight, and DNA content of the ventral prostate as that produced in R-3327 G tumor-bearing rats which experienced an antitumor response. These results suggest that SK&F 105657 can produce antitumor effects if a substantial reduction in tissue DHT is achieved. Such reduction in tissue DHT, secondary to inhibition of the tissue 5 alpha-reductase enzyme, appears to be more difficult to achieve in tumors than in the normal prostate. In order to achieve such a DHT reduction in tumor tissue, prostatic cancers with low 5 alpha-reductase activity could be treated with SK&F 105657 on a dose regimen that lowers serum DHT to surgical castration levels, while concomitantly inhibiting the already low tumor tissue 5 alpha-reductase activity.
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PMID:Response of rat and human prostatic cancers to the novel 5 alpha-reductase inhibitor, SK&F 105657. 164 69

Reliable predictors of response for prostate cancer patients undergoing hormonal therapy are lacking. This study investigates the possibility that tumor proliferation rates might predict tumor behavior for these patients. The growth fraction of metastatic prostate cancer biopsy specimens obtained before androgen withdrawal therapy was evaluated by Ki-67 antibody immunohistochemical study to determine whether a higher tumor growth fraction was associated with a shorter time to tumor progression after therapy. The percentage of Ki-67-positive malignant epithelial nuclei in the primary tumors of 17 patients ranged from 1.7% to 7.5% (median, 2.5%). When patients were divided into two response groups according to the median time to progression, poor responders (time to progression less than 20 months) and good responders (greater than or equal to 20 months) had similar growth fractions (3.5 +/- 0.5% versus 3.1 +/- 0.6% Ki-67-positive nuclei, respectively). However, when patients were divided into two groups based on the median growth fraction, patients with a high growth fraction (greater than 2.5% Ki-67-positive nuclei) tended to have a shorter time to progression (median, 10 months) than patients with a low (less than 2.5%) growth fraction (median time to progression, 25 months), although statistical significance was not reached. Despite this interesting trend, Ki-67 immunostaining was not accurate to predict the time to progression in individual patients undergoing hormonal therapy. Reliable prediction of growth rates may require measurement of both cell proliferation and cell death rates.
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PMID:Determination of growth fraction in advanced prostate cancer by Ki-67 immunostaining and its relationship to the time to tumor progression after hormonal therapy. 171 May 38

Fibroblasts are important contributors to both benign and malignant growth of prostate epithelial cells in vivo. In the human prostate cancer model that we have established, we can grow human LNCaP tumors reproducibly in athymic mice by coinoculating the animals with human LNCaP epithelial cells plus fibroblasts derived from either the prostate or bone; human lung, normal rat kidney, and embryonic mouse fibroblasts were inactive. We have delivered conditioned medium isolated from competent fibroblasts directly to sites where the tumor cells were injected and found that the conditioned medium alone confers tumorigenicity. Further studies of the mechanism of fibroblast-epithelial interaction have indicated that close metabolic cooperation between fibroblast and epithelial cells, involving the production of growth factors by the epithelial cells and the production of extracellular matrices and growth factors by the fibroblasts (assayed in vitro), is important in promoting prostate tumor growth in vivo. We have also investigated the possible in vivo interaction between extracellular matrix proteins such as laminin, collagens, heparan sulfate proteoglycans and Matrigel and prostate epithelial cells. Selective extracellular-matrix components were found to confer tumorigenicity to the prostate epithelial cells. Moreover, extracellular-matrix components were observed to induce cancer cell differentiation and alter permanently the morphology, gene expression and tumorigenic potential of the cancer epithelial cells.
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PMID:Fibroblasts are critical determinants in prostatic cancer growth and dissemination. 172 35

LY181984 is a compound in a series of orally active diarylsulfonylureas with broad spectrum in vivo activity against syngeneic rodent and human xenograft tumor models. The PAIII rat prostatic adenocarcinoma model was used to evaluate the effects of this antitumor agent on the lymphatic and pulmonary metastasis of the tumor in male Lobund Wistar rats. LY181984 was inactive against the proliferation of PAIII cells in vitro. Following subcutaneous implantation of 10(6) PAIII cells in the tail, oral administration of LY181984 (25.0, 50.0, or 100.0 mg./kg./day) for 30 days had no significant effects on body weight gain. LY181984 treatment produced significant (p less than 0.05) dose-dependent inhibition of primary tumor growth in the tail (max. inhibition = 46% from untreated control levels). In these same animals, LY181984 administration produced significant (p less than 0.05) dose-dependent inhibiton of PAIII metastasis from the primary tumor in the tail to the gluteal and iliac lymph nodes (maximal responses = 79% and 80% from control values, respectively). PAIII metastasis to the lungs was significantly inhibited by oral LY181984 treatment. Numbers of pulmonary foci in PAIII-bearing rats were significantly (p less than 0.05) reduced by LY181984 administration in a dose-dependent manner (maximal reduction = 78% from control values). While the non-toxic doses (less than 100.0 mg./kg./day for 28 days) of LY181984 produced marked decreases in tumor growth and metastasis, administration of the compound had no effect on the survival of PAIII-bearing rats. These data support the contention that LY181984 represents a new class of orally active antitumor and antimetastatic agents with potential efficacy in the treatment of hormone-insensitive prostatic cancer. Further studies are needed to define maximal efficacy of LY181984 and other sulfonylurea agents in urogenital solid tumor animal models.
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PMID:Inhibition of PAIII rat prostatic adenocarcinoma growth and metastasis by a new diarylsulfonylurea antitumor agent, LY181984. 173 31

We found previously that transforming growth factor-beta 1 (TGF beta 1) mRNA levels are markedly elevated in rat prostate cancer (Dunning R3327 sublines) compared to levels in normal prostate. Our goal was to determine whether elevated expression of TGF beta 1 is biologically relevant to prostate cancer growth in vivo. We chose as our model the R3327-MATLyLu prostate cancer epithelial cell line, which produces metastatic anaplastic tumors when reinoculated in vivo. Our approach was to stably transfect MATLyLu cells with an expression vector that codes for latent TGF beta 1 and to isolate subclones of cells that over-expressed TGF beta 1 mRNA. We also isolated a subclone of MATLyLu cells transfected with a control vector lacking the TGF beta 1 cDNA insert. We then studied the growth of these cells in vivo and in vitro. Twenty days after sc inoculation of 10(6) cells in vivo, TGF beta 1-overproducing MATLyLu tumors were 50% larger, markedly less necrotic, and produced more extensive metastatic disease (lung metastases in 73% of all lobes and lymph node metastases in 88% of animals) compared to control MATLyLu tumors (lung metastases, 21%; lymph node metastases, 7%). Thus, TGF beta 1 produced in vivo is biologically active and can promote prostate cancer growth, viability, and aggressiveness, perhaps via effects on the host and/or on the tumor cells themselves. When followed in vitro, TGF beta 1-overproducing cells became growth inhibited, but this effect was transient as cells subsequently resumed proliferating. Growth inhibition was due to TGF beta, because it could be prevented by TGF beta-neutralizing antibody. Therefore, prostate cancer cells can activate and respond to secreted latent TGF beta 1, and although the cells are transiently inhibited in vitro, there is no net inhibition of growth. The ability of the cells to respond to endogenously produced TGF beta 1 suggests that TGF beta 1 overexpression enhances tumor growth in vivo at least in part via an effect of TGF beta 1 on the tumor cells themselves.
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PMID:Transforming growth factor-beta 1 overproduction in prostate cancer: effects on growth in vivo and in vitro. 173 67

The transplantable androgen-dependent human prostate tumor models PC-82 and PC-EW were used to study whether low levels of testosterone and androgens of adrenal origin were capable of stimulating the growth of prostatic carcinoma cells in these tumor models. At all circulating plasma testosterone levels applied in this study, much lower levels of dihydrotestosterone were found in PC-EW tumor tissue than in PC-82 tumor tissue. Nevertheless, both prostate tumor models had a similar threshold level of dihydrotestosterone for growth stimulation, i.e. 3-4 pmol/g tissue. This critical androgen level for tumor growth amounted to 2-3 times the tissue level found in castrated animals. At this threshold level approximately 2% of the cells showed proliferative activity, as assessed by bromodeoxyuridine incorporation into DNA. The adrenal androgen dehydroepiandrosterone did not stimulate PC-82 tumor growth, whereas androstenedione did induce a moderate increase in tumor volume. It is concluded that the adrenal androgen androstenedione exerts a stimulating effect on prostatic cancer cells when its conversion results in intra-tissue testosterone and dihydrotestosterone levels exceeding the threshold level for tumor growth.
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PMID:Pharmacia Award 1990. The biological significance of low testosterone levels and of adrenal androgens in transplantable prostate cancer lines. 182 56

Prostate cancer is a rather common and severe disease in man. It affects the age beyond 50, a tendency being recently observed towards affecting subjects of younger age. In the early stage the symptoms are scarce and vague. The diagnostic possibilities of ultrasound examination, intravenous urography, computer axial tomography and biopsy specimen examination were compared in patients with prostate cancer. The authors consider the possibilities of transabdominal and transrectal echography for diagnosis of prostate cancer to be superior to those of intravenous urography. H. Watanabe even recommends and uses transrectal echography as screening method. The possibilities and results of transrectal echography and computer axial tomography for evaluating tumor growth and infiltration outside the prostate capsule are compared. Ultrasound examination is recommended as a more exact method, with a view to radical prostatectomy. The good correlation of the echographic patterns with tumor development are also recorded.
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PMID:[A comparative evaluation between transrectal echography, venous urography, computerized axial tomography and morphology in patients with prostatic carcinoma]. 184 59


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