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)

Benign prostatic hyperplasia (BPH) involves proliferation of smooth muscle cells and increased deposition of extracellular matrix (ECM). We recently found that pentosan polysulfate (PPS) has marked effects on growth and ECM of smooth muscle cells derived from vascular tissues. We examined smooth muscle cells cultured from human prostates and the effects of PPS on their growth and ECM production. Fragments of surgical prostatectomy specimens were diced, digested with collagenase (0.01%), and placed in culture medium supplemented with 20% fetal bovine serum. Outgrowths of elongated cells were characterized by light microscopic examination and immunohistochemical techniques by the presence of F-actin, alpha-smooth muscle actin, and myosin, which is a characteristic of smooth muscle cells. Two independent isolates were propagated, and growth curves and ECM production were assessed in the presence and absence of PPS (10 or 100 microg/ml). PPS decreased cell number beginning at day 1 and throughout the incubation period, up to 4 days. The amount of the ECM degradative enzymes, metallo-proteinases MMP-9 and MMP-2, was examined by zymography. PPS did not alter the amount of MMP-2 in the supernatants but MMP-9 was increased 234.4 +/- 17.23-fold over control cells. Tissue inhibitor of MMP (TIMPS), examined by reverse zymography, increased 200% over control. The amount of alpha I type (IV) and alpha I type (I) collagen released in the supernatant, measured by ELISA, significantly decreased in PPS-treated cultures. In conclusion, we found that the administration of PPS decreased proliferation as well as ECM production in prostate smooth muscle. Since smooth muscle proliferation and ECM are involved in the pathophysiology of BPH, PPS may have therapeutic potential.
Prostate Cancer Prostatic Dis 2003
PMID:Pentosan polysulfate decreases prostate smooth muscle proliferation and extracellular matrix turnover. 1280 72

Treatment of incontinence and bladder complaints in the male should be directed to the cause whenever possible. Frequently, however, only symptomatic therapy is possible. Urge incontinence or overactive bladder due to obstruction should primarily be treated by eliminating the obstruction. Medical and surgical treatment methods are available for benign prostatic hyperplasia, bladder neck hypertrophy and prostatic cancer. In contrast, bladder neck sclerosis and uretheral strictures can only be treated surgically. Anticholinergics are primarily indicated if urge symptoms/incontinence persist after obstruction has been relieved or if urge incontinence occurs without obstruction. Seldom, in special cases injection of Botulinustoxin A or augmentation of the bladder may be indicated. Another possible cause of urge symptoms is urinary tract infection. This should be adequately treated according to resistance studies and the cause of the infection determined. In cases of overflow incontinence the infravesicle obstruction must be sought and treated. If limited detrusor contractability is the cause of overflow incontinence and the bladder cannot be emptied through pressmicturition, parasympathicometics may be of help. By insufficient effect, the procedure of intermittent self-catheterization must be taught. If this is not possible, the last resort is placement of a transuretheral or percutaneous catheter for continuous drainage. Stress incontinence is a rare complication in men, usually following prostatic surgery. It can be treated conservatively with pelvic floor training and alpha-adrenergic receptor agonists and if necessary surgically with submucosal collagen or silicon injections in the sphincter area or implantation of a sphincter prosthesis. Supravesicular urinary diversion is occasionally necessary after conservative and less invasive surgical measures have been exhausted and symptomatic suffering persists. Neurogenic disturbances in bladder capacity and/or emptying can be treated conservatively, medically, surgically or a combination of these depending upon the site of the lesion and the resulting urodynamic patterns.
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PMID:[Conservative and surgical therapy of urinary incontinence and bladder complaints in the man]. 1280 98

Extensive scientific literature data point to reciprocal interactions between prostate stromal cells and prostate cancer cells that likely regulate tumor progression. To investigate whether these intratumoral-reactive stromal cells in human prostate cancer are predictive of survival, tumor stroma volume and specific stroma markers were quantitated by using tissue microarrays (index tumors of 847 patients), and the results were analyzed relative to the recurrence-free survival data set for these patients. Tumor tissue was evaluated with Masson's trichrome stains and by immunohistochemistry with antibody probes to smooth muscle alpha-actin, desmin, vimentin, pro-collagen type I, and calponin. The relative volume of intratumor stroma (5% stroma, grade 0; 5-15%, grade 1; 15-50%, grade 2; >50%, grade 3) and the expression index of stromal marker (staining intensity grade x percentage of positive cells per field) were quantitated and analyzed. Interpretable data were obtained from 545 patients. Statistical analysis of the survival data set showed that the volume of reactive stroma in the tumor was a significant predictor of disease-free survival. Stroma volume was most optimal as an independent predictor in tumors containing stroma, defined as Gleason 7 and lower grades. Of interest, tumors with either little to no stroma or tumors with abundant stroma each showed reduced recurrence-free survival. For specific stromal markers, reduced desmin and smooth muscle alpha-actin were hallmarks of cancer-associated reactive stroma relative to normal fibromuscular stroma. Quantitative analysis of desmin and smooth muscle alpha-actin expression showed both to be significant and independent predictors of recurrence-free survival. This is the first study to demonstrate that nonepithelial-reactive stroma elements in prostate cancer tumors can be used as prognostic indicators. These data also add to the concept that tumors are not purely epithelial and the tumor-reactive stroma must be considered an important biological component of the cancer.
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PMID:Reactive stroma as a predictor of biochemical-free recurrence in prostate cancer. 1458 50

Prostate cancer (CaP) develops metastatic bone lesions that consist of a mixture of osteosclerosis and osteolysis. We have previously demonstrated that targeting receptor activator of nuclear factor kappaB ligand (RANKL) with osteoprotegerin (OPG) prevents the osteolytic activity of CaP and its ability to establish tumor in bone. However, OPG can block tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis, suggesting that the clinical use of OPG may prevent apoptosis of tumors mediated by TRAIL. Thus, methods to block RANKL activity, other than OPG, may be important. Accordingly, we evaluated the ability of soluble murine RANK-Fc (sRANK-Fc) to prevent progression of established CaP in a severe combined immunodeficient mouse implanted with fetal human bone. We first confirmed that sRANK did not block TRAIL-mediated apoptosis of LuCaP cells in vitro and that it did block LuCaP-conditioned media-induced osteoclastogenesis in vitro. Then, LuCaP 35 CaP cells were injected into the marrow space of the bone implanted in the severe combined immunodeficient mice implanted with fetal human bone and allowed to develop into tumors for 6 weeks. Either vehicle or sRANK-Fc was then administered for 6 weeks. sRANK-Fc diminished tumor-induced osteoblastic lesions as demonstrated by radiograph, bone mineral density measurement, and bone histomorphometry. sRANK-Fc also reduced systemic bone remodeling markers, including serum osteocalcin and bone-specific alkaline phosphatase and urine N-telopeptide of collagen. Finally, sRANK-Fc decreased serum prostate-specific antigen levels and tumor volume in the bone, which indicates decreased tumor burden. In contrast, sRANK-Fc had no effect on s.c. implanted LuCaP cells. We conclude that sRANK-Fc is an effective inhibitor of RANKL that diminishes progression of CaP growth in bone through inhibition of bone remodeling.
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PMID:Soluble receptor activator of nuclear factor kappaB Fc diminishes prostate cancer progression in bone. 1463 17

Arachidonate 12-lipoxygenase (LOX) converts arachidonic acid to 12(S)-hydroxyeicosatetraenoic acid (HETE), a bioactive lipid implicated in tumor angiogenesis, growth, and metastasis. Alteration in 12-LOX expression or activity has been reported in various carcinomas including prostate carcinoma. However, little is known about the impact of the altered expression or activity of 12-LOX on tumor metastasis. In the present study, we examined whether or not an increase in 12-LOX expression in human prostate carcinoma cells can modulate their metastatic potential. We report that increased expression of 12-LOX in PC-3 cells caused a significant change in cell adhesiveness, spreading, motility, and invasiveness. Specifically 12-LOX transfected PC-3 cells were more adhesive toward vitronectin, type I and IV collagen, but not to fibronectin or laminin, than cells transfected with control vector. Increased spreading on vitronectin, fibronectin, collagen type I and IV also was observed in 12-LOX transfected PC-3 cells when compared to control PC-3 cells. The increased spreading of 12-LOX transfected PC-3 cells was blocked by treatment with 12-LOX inhibitors, baicalein and CDC. 12-LOX transfected PC-3 cells were more invasive through Matrigel than cells transfected with control vector. In vivo, tumor cell invasion to surrounding muscle or fat tissues was more frequent in nude mice bearing s.c. tumors from 12-LOX transfected PC-3 cells than in those from control vector transfected cells. When injected via the tail vein into SCID mice with implanted human bone fragments, there was an increase in tumor metastasis to human bone by 12-LOX transfected PC-3 cells in comparison to control vector transfected cells. Taken together, our data suggest that an increase in 12-LOX expression enhances the metastatic potential of human prostate cancer cells.
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PMID:Increased metastatic potential in human prostate carcinoma cells by overexpression of arachidonate 12-lipoxygenase. 1466 97

Prostate cancer is the most common cancer in men and second in the cancer-related frequency of mortality. Matrix metalloproteinases (MMPs) are involved in tumor invasion and metastasis in various malignancies. MMP-2 and MMP-9 are capable of digesting collagen type IV. Numerous studies have demonstrated an association between increased MMP-2 and -9 expression and tumor progression in various tumors. In this study, the expression and activities of MMP-2 and -9 were assessed in serum probes and tumor tissue from core needle biopsies and radical prostatectomies of 97 patients. MMP-2 and -9 serum expression was analyzed in a subgroup of 31 patients. MMP-9 serum expression was significantly increased in tumor patients and correlated with tumor grade. In contrast, the MMP-9 tissue expression and activity revealed no significant correlations to tumor stage or grade. The MMP-2 activity, however, showed a positive correlation for MMP-2 with tumor stage. Increased activity was predominantly detected in advanced tumor stages. Immunohistochemical analysis of MMP-2 expression demonstrated a positive association with tumor grade in prostatectomy specimens. The relative expression rates in biopsies matched in 65% with those of the prostatectomies. Detection of MMP-2 in core needle biopsies seems not to be a helpful marker for diagnostic purposes.
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PMID:Expression and activity of matrix metalloproteinases-2 and -9 in serum, core needle biopsies and tissue specimens of prostate cancer patients. 1508 44

In this study, increasing contrast concentration and/or exposure time decreased the growth and adherence of transitional cell carcinoma cells. Similarly, several authors have shown that the toxicity of contrast material to vascular endothelial cells in culture is related to concentration and time of exposure; this toxicity is minimized if non-ionic, low osmolar contrast is utilized. Identical trends of increasing toxicity with increasing osmolality have been documented with kidney cell lines, vascular smooth muscle cells, myocardial cells, neural cells, human fibroblasts, rat mesenchymal cells, and rat hepatocytes. The toxicity of contrast material in malignant cells (human cervical carcinoma cell lines and prostate cancer cell lines) has also been documented. Factors other than direct cellular toxicity may also affect the ability of malignant transitional cells transported with contrast material to implant on other sites in the collecting system. Zhan et al have evaluated neutrophil adhesion to contrast-exposed vascular endothelial cells. These authors observed increasing cellular adhesion with decreasing contrast dose. This was not related to osmolality as there was no similar endothelial adhesion activation with equal osmolality solutions of non-contrast solutions. The authors felt that contrast material, therefore, caused some form of modulation of cell adhesion molecules. This theory is supported by research by Owens et al that shows increases in the adhesive properties of endothelial cells to platelets after contrast exposure, and Rasmussen et al who found decreased granulocyte adherence with contrast exposure. In our study, transitional cell carcinoma cultures were placed on a collagen substrate to encourage adherence. There was an increasing number of non-adherent cells with increasing contrast concentration and exposure time, which suggests an effect of the contrast on cellular adhesion as well (Table 1). Potier et al found that rat mesangial cells were more sensitive to the cytotoxic effects of contrast agents than the less differentiated human fibroblasts were. This might suggest that the more poorly-differentiated transitional cell carcinoma cells would not be as sensitive to contrast material as low-grade tumors. However, we did not observe any differences in the responses of high- versus low-grade transitional cell tumors to exposure to contrast material. Intravenous contrast administration can lead to multiple adverse reactions, such as cardiotoxicy, nephrotoxicy, and hemodynamic toxicity. This makes non-ionic, low-osmolality agents preferable to ionic, high-osmolality agents. However, direct introduction of material into the urinary collecting system for the evaluation of transitional cell carcinoma may be less prone to seeding of viable malignant cells if ionic, high-osmolar contrast agents are utilized. Additional considerations include potential masking of very small filling defects in the upper urinary tract through opacification with extremely concentrated contrast material. Also, cytologic abnormalities are worsened by exposure to ionic, high-osmolar contrast agents, thus, any specimens for cytologic analysis should be collected prior to utilization of any contrast agents.
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PMID:The effect of contrast material on transitional cell carcinoma viability. 1508 1

We have established a clonal DU-145 prostate cancer cell line (DU-145/AR) stably transfected with androgen receptor cDNA. We investigated the expression of integrin subunits, adhesion to extracellular matrices, the invasion of DU-145/AR prostate cancer cells. The expression of various integrin subunits and adhesion to various extracellular matrices in DU-145, DU-145/Neo and DU-145/AR cells were examined. The haptoinvasion and the haptotactic migration of these cells were investigated using a Transwell cell culture chamber assay. DU-145/AR cells exhibited lower expression of alpha6 and beta4 integrin subunits and higher expression of alpha2 and alpha5 than DU-145 cells. DU-145/AR cells showed significantly lower adhesion to fibronectin, laminin-1 and laminin-5 than DU-145/ Neo cells, whereas DU-145/AR cells showed higher adhesion to type I and type IV collagen. Haptoinvasion of DU-145/AR cells into Matrigel/fibronectin-coated filter was significantly reduced as compared with DU-145/Neo or DU-145 cells, but there was no significant difference between DU-145/AR and control cells in the haptotactic migration to fibronectin. Dihydrotestosterone (DHT) inhibited the invasive ability of DU-145/AR cells. These results indicate that androgen receptor may play a role in the regulation of adhesion to the extracellular matrices and invasion of prostate cancer cells through influencing the expression of specific integrin subunits.
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PMID:Differential expression of integrin subunits in DU-145/AR prostate cancer cells. 1537 9

Prostate-specific antigen (PSA) is a serine-protease that, in addition to cleaving semenogelins in the seminal coagulum, is able to cleave extracellular matrix glycoproteins, thereby affecting cell migration and metastasis. We here report some new activities of PSA that deserve careful consideration in the cancer context: degradation of gelatin, degradation of type IV collagen in reconstituted basement membrane (Matrigel) and activation of progelatinase A (MMP-2), but not pro-MMP-9, in a cell-free system. Since consumption of green tea has been reported to lower the risk of prostate cancer, we investigated the effects of the major flavanol of green tea, (-)epigallocatechin-3-gallate (EGCG), on expression and activity of PSA by prostate carcinoma cells. In addition to restraint of PSA expression, EGCG was found to inhibit in a dose-dependent manner all the above PSA activities, at concentrations lower than the cytotoxic serine-protease inhibitor PMSF and close to levels measured in the serum following ingestion of green tea. The activity of PSA was suppressed also by the elastase released by the inflammatory leukocytes. These results highlight new PSA activities, suggest gelatin zymography as a new convenient assay for PSA, propose EGCG as natural inhibitor of prostate carcinoma aggressiveness, but also stimulate further investigation on the role of prostatic inflammation.
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PMID:Prostate carcinoma and green tea: PSA-triggered basement membrane degradation and MMP-2 activation are inhibited by (-)epigallocatechin-3-gallate. 1538 86

The scope of this work was to determine the potential use of prostatic conventional histologic parameters and biologic factors in distinguishing between paramalignant and malignant prostatic disease, taking into account benign fragments of biopsies obtained from patients with prostatic cancer or from patients suspected to have cancer. Each prostate sample was semi-quantified for macronucleoli, mucin, crystalloid, collagen micronodules, and quantified for glands, stroma, AgNOR, and p53. The database covered 185 biopsy specimens from 136 patients: 56 samples from the same number of patients in whom all the biopsies were benign; 49 samples from patients whose biopsies showed malignant features, and 80 malignant samples. Discriminant analysis of the results showed statistical differences for four parameters: macronucleoli, mucin, gland volume, and AgNOR, allowing us to identify three patterns of prostate involvement: normal, paramalignant, and malignant. The discriminant function permitted an adequate classification of the three patterns in 84% of the cases. Normal areas showed glands with a mean volume of 38.93 microm3, inconspicuous nucleoli, low mucin production, and a mean AgNOR area of 1.26 microm2. Prostatic biopsies with prominent nucleoli and the presence of mucin (60%), gland volume of 22.31 microm3, and AgNOR area of 2.14 microm2 characterized the paramalignant condition. Malignant areas were characterized by mean glands with a volume of 8.11 microm3, prominent nucleoli, high mucin secretion (100%), and AgNOR area of 4.47 microm2. We concluded that modifications in prostate histoarquitecture and function, such as the presence of macronucleoli, volume of glands, abnormal secretion of acid mucin and AgNOR expression, represent important parameters that must be incorporated in the pathologist's evaluation of prostate biopsies to the purpose of indicating a subsequent biopsy, particulary in those patients with clinical suspicion of malignancy, and whose prostate biopsy specimen showed paramalignant areas.
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PMID:Quantitation of conventional histologic parameters and biologic factors in prostatic needle biopsy are useful to distinguish paramalignant from malignant disease. 1549 72


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