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)

Angiogenesis, the formation of new blood vessels from preexisting ones, is a fundamental stage in the metastatic pathway. For the primary tumor, this neovascularization provides nutrients and oxygen as well as a route by which metastatic tumor cells gain access to the circulatory system. Among these metastatic tumor cells, there are subgroups of cells that express an angiogenesis-inducing cells phenotype (AICs) as well as others that do not. Tumor cells not expressing the angiogenesis-inducing cells phenotype (non-AICs) invade new tissues and remain as dormant micrometastases unless they accompany AICs. Thus, either alone or with non-AICs, angiogenesis-inducing cells form rapidly growing, clinically detectable metastases. Much of the current research in this area is concentrated on the vascularization of primary tumors, but the regulation of angiogenesis by extravasating or invading tumor cells has not being extensively studied. We have developed a working model, which demonstrates that human metastatic prostate cancer cells (PC-3) appear to induce human vascular endothelial cells (HUVECs) to translocate across a Matrigel-coated 8 mm membrane. The parameters of this model (i.e. pore size, seeding-cell density, seeding times) were established using highly invasive murine melanoma cells (B16F10) seeded on murine microvascular endothelial cells (CD3). We have further modified our model in order to include a host compartment made of collagen gel, in order to mimic the in vivo site of metastases-induced angiogenesis.
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PMID:A novel in vitro system to study extravasated tumor cell-induced angiogenesis. 976 42

In in vitro angiogenesis assays, aggregates of human papilloma virus (HPV)-18-immortalized primary human prostate cancer cells (HPCA-5aHPV-18 or HPCA-10aHPV-18 cells) induced human bone marrow endothelial cells (HBMCE-1 cells) to form microvessels in three-dimensional collagen I gels after 1-2 days incubation at 37 degrees C. The microvessels aligned perpendicular to the tumor aggregates and abutted on the edges of the aggregates. The number and length of the microvessels increased significantly from day 1 to 2 (i.e., by approximately 30%). ELISAs showed that the HPCA-5aHPV-18 cells normally secreted low levels of tissue inhibitor of metalloproteinase (TIMP)-2, matrix metalloproteinase (MMP)-2, and MMP-9 but relatively high levels of TIMP-1. In contrast, HPCA-10aHPV-18 cells secreted high levels of MMP-2 and MMP-9 (>40 pg/microg protein) but low levels of TIMP-1 and TIMP-2 (<5 pg/microg protein). Interleukin 10 (IL-10) (15 ng/ml) induced TIMP-1 production (>15 pg/microg protein) but reduced MMP-2 and MMP-9 secretion (<5 pg/microg protein) by the HPCA-5aHPV-18 and HPCA-10aHPV-18 cells. IL-10 (15 ng/ml) and MMP-9/MMP-2 antibodies all blocked induction of microvessel formation in the coculture experiments. In contrast, IL-10 receptor antibodies and TIMP-1 antibodies countered IL-10's effects and promoted angiogenesis. The data demonstrated that IL-10 stimulation of TIMP-1 and inhibition of MMP-2 and MMP-9 secretion by prostate tumor cells can control induction of angiogenesis in vitro.
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PMID:Interleukin 10 (IL-10) inhibition of primary human prostate cell-induced angiogenesis: IL-10 stimulation of tissue inhibitor of metalloproteinase-1 and inhibition of matrix metalloproteinase (MMP)-2/MMP-9 secretion. 991 18

Cancer cell attachment to and invasion of the extracellular matrix has been associated with the metastatic potential of cell lines of the Dunning R-3327 rat prostatic adenocarcinoma model. We investigated the cell-matrix interactions of prostate tumor cells by comparing the invasive ability through reconstructed extracellular matrix and attachment upon EHS NATRIX (natural extracellular matrix), fibronectin, laminin, and collagen Type IV. We observed a correlation between metastatic potential and substrate dependence of attachment in prostate cancer cells. Nonmetastatic AT-1 cells possessed a higher adhesive potential to extracellular matrix components than the highly metastatic cells (ML, MLL and AT-3). It was also found that the invasive potential of the three highly metastatic cell lines was significantly higher than that of the nonmetastatic cell line. Here, it is reported that the ability to traverse a matrigel matrix correlates with their metastatic potential. These observations suggest that the extracellular matrix components are highly involved in influencing prostate cancer cell activities. In addition, we investigated the effects of two differentiation agents, retinoic acid (RA) and difluoromethylornithine (DFMO), on the adhesive and invasive profiles of the tumor cells. After treatment with both agents, adhesion was increased to levels not different from nonmetastatic cells. Furthermore, the ability of highly metastatic cells to traverse a matrigel barrier was significantly reduced after treatment with both differentiation agents. These results suggest that RA and DFMO are capable in reversing the metastatic potential of prostate cancer cells in vitro and may give a possible insight into their role as potential therapeutic agents in vivo.
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PMID:Invasive potential and substrate dependence of attachment in the dunning R-3327 rat prostate adenocarcinoma model. 1064 Sep 2

Urinary incontinence following radical retropubic prostatectomy is a serious medical and psychological complication with a major negative impact on quality of life in patients with localized prostate cancer. The overall incidence of this complication is higher than 2% regardless whether the surgery has been done by the retropubic or perineal approach. The correct diagnosis of incontinence is based on urodynamic investigations. Two main causes of incontinence are detrusor hyperactivity and sphincteric insufficiency. The best prevention for postoperative incontinence of urine is meticulous surgery. Treatment options of incontinence are pharmacological or surgical (injections of collagen, autologous fat or implantation of artificial urinary sphincters).
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PMID:[Urinary continence after radical retropubic prostatectomy]. 1074 39

The mechanisms responsible for the emergence of clinically advanced prostate cancer (PC) are incompletely understood. Recent studies suggest that altered tumoral apoptosis with disordered cell proliferation sustains advanced disease and may account for the phenomena of anti-androgen therapeutic resistance. Previous inquiry has focused primarily on faulty intracellular mechanisms with limited scrutiny of the extracellular matrix including fibronectin and collagen type 4. We evaluated cell proliferation with Ki-67 immunoassay/image analysis and apoptosis by TUNEL staining and Bcl-2 immunoassay/image analysis in LNCaP and PC-3 human PC cell lines at baseline and following propagation on fibronectin and collagen type 4-coated coverslip substrate. Cell cultures showed differing proliferative and apoptosis characteristics at baseline, with the LNCaP cell line showing relatively higher proliferation and apoptosis rates than the PC-3 cell line. Cell proliferation and apoptosis were statistically significantly decreased in both cell lines following propagation on fibronectin. Bcl-2 expression was significantly increased among both cell lines following propagation on fibronectin. In contrast, cell proliferation, apoptosis, and Bcl-2 expression showed insignificant changes in both cell lines following uncoated coverslip and collagen type 4 matrix propagation. Our findings showed that fibronectin influences cell proliferation, apoptosis, and Bcl-2 expression similarly among LNCaP and PC-3 PC cell lines. It is likely that the altered rates are independent of the androgen status of the cell line and are mediated through a nonhormonal mechanism.
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PMID:Fibronectin influences cellular proliferation and apoptosis similarly in LNCaP and PC-3 prostate cancer cell lines. 1086 57

The report discusses a study of pyridinoline (Pyd) and deoxypyridinoline (Dpyd) as biochemical markers of bone resorption as well as total bone alkaline phosphatase level (APh) and that of its bone fraction as criteria of osteogenesis in skeletal lesions in breast, prostate and lung cancer and multiple myeloma. The investigation established a significantly enhanced Pyd and Dpyd excretion with urine and increased blood-serum APh levels in skeletal cancers (n = 271) as compared with healthy subjects (n = 173) and patients without bone metastases (n = 94). A case has been made for determination of total excretion of Pyd crosslinks of collagen to diagnose bone metastases. Most pronounced hyperenzymemia was found in prostate cancer which points to the leading role of APh as a bone metastasis marker. Pyd and Dpyd excretion and APh levels were significantly higher among patients multiple metastases with than in those with single bone metastases. The universality of pyridinoline crosslinks as skeletal damage markers has been confirmed by establishing a significant correlation between drug and therapeutic effect for Pyd and Dpyd only, in patients receiving ibandronate.
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PMID:[The biochemical markers of bone remodeling in cancer patients with skeletal involvement]. 1097 74

The objective of the present study is to examine the role of prostate stromal cells on growth and progression of prostate cancer. Co-inoculation of androgen-independent carcinoma cells (PC-3 and CA-7T2) with prostate-derived stromal (P-ST) cells significantly enhanced the growth of carcinoma cells in athymic nude mice. For the in vitro study, a three-dimensional co-culture system was used. It consisted of two layers of collagen gel. Stromal cells were suspended in the lower layer, whereas cancer cells were suspended in the upper layer. Compared to the control culture, the presence of P-ST cells in the lower collagen layer significantly stimulated the growth of carcinoma cells. Such an effect was not demonstrated when carcinoma cells were co-cultured with either bone marrow-derived or skin-derived stromal cells. We identified hepatocyte growth factor (HGF) as the principal growth factor released by P-ST cells but not by bone marrow-derived or skin-derived stromal cells. Neutralizing antibodies against HGF completely abrogated the stimulatory effect of P-ST cells. Exogenous HGF likewise stimulated the growth of carcinoma cells in vitro and in vivo. These results suggest that HGF produced by P-ST cells is a paracrine growth factor that stimulates the growth of androgen-independent prostate cancer cell lines.
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PMID:Hepatocyte growth factor secreted by prostate-derived stromal cells stimulates growth of androgen-independent human prostatic carcinoma cells. 1098 Jan 19

The objective of this study was twofold: (1) to determine if a cellular digestion process can facilitate examination of the morphology of the connective tissue framework of the prostate, and (2) to examine the connective tissue framework in normal prostate tissue, benign prostatic hyperplasia (BPH) and prostate cancer. Ten prostate glands were examined. Using the Ohtani method of digestion, the cellular elements were removed. This enabled scanning electron microscopy analysis of the connective tissue framework within the prostatic tissue. Light microscopy of tissue blocks determined the histology of specimens. The prostate is supported by a highly structured network of collagen fibres. This network of fibres varies in normal and diseased states. In benign prostatic hyperplasia, the collagen network is dense, with an increased number of fibres. In prostatic adenocarcinoma, there is non-uniform swelling with a loss and disintegration of collagen fibres. In conclusion, sodium hydroxide cellular digestion provides an excellent method for demonstrating the connective tissue framework of prostatic tissue. The morphological changes in collagen fibres in normal prostate, benign prostatic hyperplasia and prostatic adenocarcinoma have implications for prostate growth in normal and diseased states.
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PMID:The connective tissue framework in the normal prostate, BPH and prostate cancer: analysis by scanning electron microscopy after cellular digestion. 1112 7

Type I collagen cross-linked N-telopeptide (NTx) in urine, the degraded form of type I collagen cross-linked in bone, has been evaluated as a marker of bone resorption. In this study, the clinical usefulness of NTx as a marker of bone metastasis of prostate cancer was compared with that the carboxyterminal propeptide of type I procollagen (PICP), the aminoterminal propeptide of type I procollagen (PINP), and the pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) in serum. We assessed 37 cases of prostatic cancer in which the diagnosis had been confirmed pathologically. The patients were 15 patients with prostatic cancer with bone metastasis (before treatment or during a relapse) (Group 1); 11 patients, with bone metastasis, but for whom treatment was effective and condition had stabilized (Group 2); and 11 patients, with localized prostatic cancer and no evidence of bone metastasis (Group 3). The serum PICP, PINP, and ICTP levels and concentration of NTx in urine were compared among the three groups with the Mann-Whitney U test, with p values less than 0.05 considered significant. Urine NTx concentrations in Groups 1, 2 and 3 were 539.3 +/- 202.9, 160.6 +/- 97.6 and 48.6 +/- 7.6 nMBCE/mMCr, respectively. The differences between the Group 1 and Group 2 and between Group 1 and Group 3 were significant (p < 0.01 and p < 0.001). The differences between Group 1 and Group 3 and between Group 2 and Group 3 were significant for serum PICP, PINP and ICTP concentrations (p < 0.05). The correlation coefficient between urine NTx and each serum bone metabolic marker was 0.8 for PICP, 0.4 for PINP and 0.5 for ICTP. These bone metabolic markers are promising clinical markers of bone metastatic and may be useful for prediction of therapeutic efficacy and recurrence in bone and quantification of the extent of bone metastates.
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PMID:[Clinical usefulness of cross-linked N-telopeptide of type I collagen (NTx) as a bone metastatic marker in patients with prostate cancer--comparison with serum PICP, PINP and ICTP]. 1121 2

We examined how prostate stromal cell-derived hepatocyte growth factor (HGF) affects invasion of prostate cancer cells through tumor-stromal interaction. The effects of HGF, various growth factors [transforming growth factor (TGF)-alpha, TGF-beta 1, basic fibroblast growth factor, keratinocyte growth factor, and platelet-derived growth factor], and conditioned medium (CM) from prostate stromal cells (PrSC) on prostate cancer cells (LNCaP, PC-3 and DU145) were determined by collagen gel invesion assay. DU145 cells and PrSC were co-cultured for matrigel invasion chamber assay. LNCaP and PC-3 cells did not respond to any of the factors examined. Invasion of DU145 cells into the collagen gel matrix was induced by HGF and TGF-beta 1, but not by any of the other factors tested. When DU145 cells were cultured in CM from PrSC or co-cultured with PrSC, the cells acquired invasive potential, and this invasion was inhibited by an antibody against HGF, but not against TGF-beta 1. Induction activity of CM from cancer cells to stimulate HGF production by PrSC was studied by ELISA method and Western blotting. Native type HGF production in PrSC was enhanced by some unknown inducer(s) produced by cancer cells. In summary, PrSC-derived HGF enhanced invasive activity of the prostate cancer cell line DU145 through tumor-stromal interaction wherein DU145 cells secreted some HGF-inducer(s) for PrSC.
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PMID:[Role of hepatocyte growth factor in invasion of prostate cancer cell lines through tumor-stromal interaction]. 1121 8


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