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)

Elf-1 is a member of the Ets transcription factor family that regulates the genes involved in cellular growth and differentiation. Enhanced expression of Elf-1 has been reported in prostate cancer, breast cancer, and osteosarcoma. The aim of this study was to elucidate the involvement of Elf-1 in ovarian carcinogenesis. We analyzed serial frozen tissue sections from 26 patients with epithelial ovarian carcinoma and 10 patients with benign cystadenoma of ovary for Elf-1 protein expression, using fluorescent immunohistochemistry. We analyzed the relationship between the percentages of Elf-1-stained cells and patient characteristics, including histological classification, clinical stage, histological grade, clinical outcome, and survival rate. Elf-1 was weakly detected in some benign cystadenomas (0-5.5%). There was, however, abundant Elf-1 immunoreactivity in the nucleus of the ovarian carcinoma cells along with a little cytoplasmic staining. Scoring on the basis of the percentage of nuclear-positive cells indicated that nuclear Elf-1 expression was significantly associated with PCNA-labeling index (p=0.04), clinical stage (p<0.01), histological grade (p<0.01), and clinical outcome (p=0.02). However, there was no relationship between Elf-1 expression and histological classification. Survival data were available for all patients and demonstrated that Elf-1 expression was significantly associated with poor prognosis (p<0.01). Our results demonstrate that Elf-1 expression in ovarian carcinoma correlates with the malignant potential of this tumor.
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PMID:The significance of Elf-1 expression in epithelial ovarian carcinoma. 1288 51

Prostate carcinoma-derived factors induce a proliferative response in osteoblasts. The present study investigated the involvement of MAP kinase in the osteoblastic reaction of osteocytes and the response of 1alpha,25-hydroxy-vitamin D3 (1,25-vitD3)-pretreated osteoblasts. Conditioned media (CM) from prostate, colon, pancreatic, renal cell and breast cancer cell lines were tested on their proliferative activity using murine osteoblast-like MC3T3-E1 cells, MG63 human osteosarcoma cells and immortalized human osteoblasts (AHTO-7). Changes in osteoblastic activities of the supernantants were measured in the presence of MAP kinase inhibitors and following 1,25-vitD3-induced differentiation of the target osteoblasts. Supernatants of prostate cancer cells stimulated proliferation of osteoblasts in all three indicator cell lines, with AHTO-7 exhibiting the most significant correlation to human primary osteoblast cultures. 1,25-vitD3 induced the differentiation marker alkaline phosphatase (ALP) in MC3T3-E1 and AHTO-7, but only to a minor degree in MG63 cells. 1,25-vitD3-induced differentiation reduced the proliferative response to CM from several cell lines in MC3T3-E1 and MG63 to a minor degree, whereas in AHTO-7 cells the osteoblastic reaction was reduced for 2/4 pancreatic, 3/3 colon and 1/1 renal cancer CMs, however not for 3/3 prostate cancer CMs. Stimulation of AHTO-7 cells by CM from prostate cancer lines is inhibited significantly by MEK1 kinase inhibitor PD 98059 in contrast to CMs derived from other carcinomas, except ACHN renal cancer cells. The findings in the present study demonstrate that human AHTO-7 cells seem to represent a valid human system to monitor osteoblastic activity, especially in respect to 1,25-vitD3-induced differentiation. Vitamin D3-induced differentiation has no direct effect on prostate cancer-derived osteoblastic activity in the same cell line in vitro, which however, could be reversed by disruption of the signal transduction at the MAP kinase level, revealing a new target for the inhibition of prostate cancer-associated bone formation.
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PMID:Effects of 1alpha,25-dihydroxy-vitamin D3 pretreatment and MAP kinase inhibitor PD 98059 on response of osteoblasts to prostate-derived osteoblastic factors. 1288 36

Tissue inhibitors of metalloproteinases (TIMPs) have been shown to perform several biological functions in tumor promotion, principally by their action of inhibiting matrix metalloproteinases (MMPs) at different steps of the metastatic process. In particular, TIMP-2 is involved in a functional complex with the membrane-type 1 (MT1) MMP to convert the secreted MMP-2 progelatinase into the fully active proteolytic enzyme. We used the human, androgen-sensitive prostate carcinoma cell line LNCaP in coculture with the human osteosarcoma cell line OHS to experimentally address the possibility of androgen-dependent regulatory effects on the functional MT1-MMP/TIMP-2/MMP-2 complex upon interaction between prostate carcinoma and osteoblastic cells in metastasis of prostate cancer to bone. In the LNCaP cells a gradual, time-dependent decline in TIMP-2 mRNA expression was observed in the presence of the synthetic androgen analogue R1881 (100 nM), reaching approximately 25% of the control level after 48 h of incubation. Consistent with this, the accumulation of secreted TIMP-2 in media from R1881-treated cells was significantly inhibited already after 3 h. Neither MMP-2 gelatinolytic activity nor expression of MT1-MMP was detected in LNCaP cells. In contrast, the OHS cells showed membrane-associated MT1-MMP expression as well as MMP-2 secretion. However, R1881 treatment of the LNCaP/OHS coculture model did not seem to change the overall proteolytic activity of the MT1 -MMP/TIMP-2/MMP-2 complex. Hormonal control of TIMP-2 expression in prostate carcinoma cells has not been previously reported, but whether such regulation has any functional role in the development of osteoblastic metastases in prostate cancer is still unclear.
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PMID:The metalloproteinase inhibitor TIMP-2 is down-regulated by androgens in LNCaP prostate carcinoma cells. 1459 88

Stromal-epithelial interaction contributes to local prostate tumor growth, androgen-independent progression and distant metastasis. We have established in vitro coculture and in vivo chimeric tumor models to evaluate the roles of stromal cells isolated from either osteosarcoma or normal bone, a site where prostate cancer cells frequently metastasize, in contributing to the growth and survival of human prostate cancer cells. We have evaluated extensively the effects of toxic gene therapy using luciferase-tagged chimeric human prostate cancer models both in vitro and in vivo. In the in vitro cocultured cell model, we assessed cancer cell growth and residual cellular proteins after targeting either prostate cancer epithelial cells alone or both prostate cancer and bone stromal cells. In the in vivo animal model, we measured tumor volume and serum prostate-specific antigen (PSA) in mice bearing chimeric prostate tumors comprised of human prostate tumor cells and normal bone stromal cells. Our results demonstrated that: (1) The rate of human prostate cancer cell growth in vitro is accelerated by coculturing with human and rat osteosarcoma or normal mouse bone marrow stromal cell lines. No growth stimulation was noted when cocultured with a human prostate epithelial cell line. (2) Disabling the growth of normal bone stromal cells using transgenic targeting with a bystander gene, herpes simplex virus thymidine kinase (hsv-TK), plus the pro-drug ganciclovir (GCV) or acyclovir markedly depressed the growth of cocultured human prostate cancer cells in vitro and human prostate cancer-mouse normal bone stroma chimeric tumors in vivo. (3) By cotargeting both human prostate cancer and normal mouse bone stromal cells in vitro with an adenoviral construct, Ad-hOC-TK (a replication-defective Ad5 vector with the bystander transgene hsv-TK under the control of a human osteocalcin (hOC) promoter) plus GCV4, we observed greater inhibition of tumor cell growth than by targeting a single cell compartment with Ad-PSA-TK (a vector construct similar to Ad-hOC-TK except that the transgene expression is under regulation by a full-length human PSA promoter). These results, taken together, established a basic principle that cotargeting both tumor and its supporting stroma is more efficacious than targeting a single cell compartment in the treatment of human prostate cancer bone metastasis. This principle can be applied to other clinical conditions of cancer growth where stroma contribute to the overall growth and survival potential of the cancer.
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PMID:Cotargeting tumor and stroma in a novel chimeric tumor model involving the growth of both human prostate cancer and bone stromal cells. 1469 56

A case of osteosarcoma in pelvic bone following radiation therapy for prostate cancer is reported. A 74-year-old patient was diagnosed with prostate cancer 10 years ago and started on the endocrine therapy with LH-RH agonist. He had no apparent distant metastasis, and received radiation therapy 8 years ago. He has complained of low back pain since several months ago. A high uptake on bone scintigram and osteolytic and osteoblastic damages on CT were noted in pubic bone and sacrum. The PSA level was less than 0.2 ng/ml. Pathohistological diagnosis by biopsy of the pubic bone was chondroblastic type osteosarcoma, showing an atypical cell proliferation with osteoid. Immunostaining for nonepithelial marker vimentin was positive. He underwent heavy ion radiation therapy for osteosarcoma at the National Institute of Radiological Sciences. Osteosarcoma is one of the rare delayed complications after radiation therapy and requires biopsy for correct diagnosis.
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PMID:[A case of osteosarcoma in pelvic bone following radiation therapy for prostate cancer]. 1497 43

Clusterin/Apolipoprotein J (CLU) is a heterodimeric ubiquitously expressed secreted glycoprotein that is implicated in several physiological processes and is differentially expressed in many severe physiological disturbances, including tumor formation and in vivo cancer progression. Despite extensive efforts, clarification of CLU's biological role has been exceptionally difficult and its precise function remains elusive. Short RNA duplexes, referred to as small interfering RNAs (siRNAs), provide a new approach for the elucidation of gene function in human cells. Here, we describe siRNA-mediated CLU gene silencing in osteosarcoma and prostate human cancer cells and illustrate that CLU mRNA is amenable to siRNA-mediated degradation. Our data demonstrate that CLU knockdown in human cancer cells induces significant reduction of cellular growth and higher rates of spontaneous endogenous apoptosis. Moreover, CLU knockdown cancer cells were significantly sensitized to both genotoxic and oxidative stress induced by chemotherapeutic drugs and H(2)O(2), respectively. These effects were more pronounced in cell lines that express high endogenous steady-state levels of the CLU protein and occur through hyperactivation of the cellular apoptotic machinery. Overall, our results reveal that, in the distinct cellular contexts of the osteosarcoma and prostate cancer cells assayed, CLU is a central molecule in cell homeostasis that exerts a cytoprotective function. The described CLU-specific siRNA oligonucleotides that can potently silence CLU gene expression may thus prove valuable agents during antitumor therapy or at other pathological conditions where CLU has been implicated.
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PMID:Silencing expression of the clusterin/apolipoprotein j gene in human cancer cells using small interfering RNA induces spontaneous apoptosis, reduced growth ability, and cell sensitization to genotoxic and oxidative stress. 1499 47

Osteosarcoma (OS), a malignant bone neoplasia in childhood, has poor prognosis if metastases appear in the lung. A novel therapeutic approach could consist in a gene therapeutic treatment of OS metastases. However, if promiscuous viral vectors are applied for the delivery of potentially toxic transgenes, their misdelivery into normal tissues could cause severe complications. This problem could be circumvented by application of OS-specific promoters for transgene expression control. We analysed the function of promoters described to be tumour-, osteosarcoma- or osteoblast-specific. Expression rates driven by osteoblast- specific fragments from the collagen1A1-promoter, the human Osteocalcin-promoter, the bone-sialoprotein promoter and the beta-catenin promoter depending on vitamin supplementation were analysed in five OS cell lines, in normal lung fibroblasts and in a non-osteoblastic prostate cancer cell line (LNCaP) by dual luciferase assays. In addition, an unspecific but doxycyclin-repressible promoter construct (pAd.3r-luc) was examined. We found that all constructs were active in OS cell lines to varying extents. The complete human Osteocalcin promoter and the bone-sialoprotein promoter were partially induced by vitamin D3 or C respectively while the pAd.3r-luc activity could be shut down by doxycyclin. In contrast, the human Osteocalcin-promoter was not activated by vitamin D3 in LNCaP cells; its action remained relatively low. Interestingly, excepting the beta-catenin promoter, we measured strong activities of all promoters in lung fibroblast cells. Our study demonstrates that promoter activity should be evaluated not only for the target cells of the gene therapeutic approaches, but also for neighbouring normal tissues. Unspecific but repressible promoters could represent an alternative.
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PMID:Limited specificity of promoter constructs for gene therapy in osteosarcoma. 1537 10

Prostate cancer metastasizes predominantly to bone, where it induces osteoblastic lesions. Paracrine factors secreted by the metastatic cancer cells are thought to mediate these events. We previously isolated a novel bone metastasis-related factor (MDA-BF-1) from bone marrow aspirate samples from patients with prostate cancer and bone metastasis, and found that this factor stimulated osteoblast differentiation, possibly by interacting with a receptor on the osteoblasts. Identifying this putative MDA-BF-1 receptor biochemically requires the expression of MDA-BF-1 for receptor binding assays and for the preparation of a ligand-affinity column. We tagged MDA-BF-1 with a peptide containing a protein kinase A phosphorylation site plus a 7-histidine sequence to facilitate the labeling of MDA-BF-1 for receptor binding assay and the binding of MDA-BF-1 to an immobilized metal affinity column. The recombinant MDA-BF-1 protein (MDA-BF1-kinase-his) was expressed in Sf9 cells using a baculovirus expression system. About 0.8 mg of purified MDA-BF1-kinase-his protein was obtained from 4 x 10(8) Sf9 cells. MDA-BF1-kinase-his can be phosphorylated by PKA with a specific activity around 10(5)cpm/mug protein. Receptor binding assays using this (32)P-labeled MDA-BF-1 showed that MDA-BF-1 bound to membranes prepared from Saos-2, an osteosarcoma cell line, and C2C12, a mouse pluripotent mesenchymal precursor cell line that can be induced to become osteoblast by BMP-2. In contrast, MDA-BF-1 did not bind to membranes from PC-3 human prostate cancer cells or HEK293 human embryonic kidney cells. These observations suggest that the MDA-BF-1 receptor is expressed in cells of osteoblastic lineage. In addition to its use as a ligand for receptor binding assays, a ligand affinity column can be prepared by binding MDA-BF1-kinase-his to an IMAC for the purification of MDA-BF-1 receptor.
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PMID:Expression of recombinant MDA-BF-1 with a kinase recognition site and a 7-histidine tag for receptor binding and purification. 1591 29

The oncophilic complex of technetium-99m labeled pentavalent dimercaptosuccinic acid (99mTc(V)-DMSA) has been successfully used for the detection of primary and metastatic medullary thyroid cancer and for imaging various soft tissue tumors like lung, brain and prostate cancer. In this article, the role of 99mTc(V)-DMSA in the diagnosis of the primary tumor and metastases of osteosarcoma patients as compared to the 99mTc-MDP scan and the CT scan was studied. Twenty-eight patients with bone disease were referred to the Nuclear Medicine Department of Saint Savas Oncology Hospital in Athens from the Orthopedics Department of the same Hospital. From them, 18 (Group A) had osteosarcoma, 7 (Group B) osteomyelitis and 3 (Group C) bone fractures. The final diagnosis was made after fine needle aspiration biopsy. All patients were subjected to the 99mTc(V)-DMSA scan, the standard bone scan (99mTc-MDP) and CT scan. Group A patients showed a selective uptake of 99mTc(V)-DMSA in the primary tumor region. No abnormal 99mTc(V)-DMSA uptake was observed in the patients of Groups B and C. The 99mTc(V)-DMSA scan was found to be superior to the 99mTc-MDP and the CT scans in identifying metastases of osteosarcoma. Sensitivity was 100%, 86% and 98% respectively.
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PMID:The role of 99mTc(V)-DMSA scan as compared to 99mTc-MDP and CT scans in imaging the primary tumor and metastases of osteosarcoma. 1933 Jan 92

Gene therapy experiments in animal models have shown that apoptin expression results in tumour regression without any significant side effects. Therefore, apoptin is regarded as a potential anticancer drug for clinical applications. In this study, we analysed whether chemotherapeutic agents combined with apoptin treatment could result in enhanced cytotoxicity in human tumour cell cultures. Combined treatment with recombinant adenovirus AdAptVP3 expressing apoptin and etoposide clearly showed an additive cytotoxic effect on human osteosarcoma U2OS cells. Paclitaxel treatment combined with apoptin expression significantly inhibited the survival of p53-positive human osteosarcoma U2OS and non-small lung carcinoma A549 cells, p53-negative human osteosarcoma Saos-2 cells and p53-mutant human prostate cancer Du145 cells, already at low doses of the chemotherapeutic agent. Our results indicate that the cytotoxicity-enhancing action by the tumour-specific apoptin in combination with chemotherapeutic agents might offer an effective and safe antitumour therapeutics.
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PMID:Additive cytotoxic effect of apoptin and chemotherapeutic agents paclitaxel and etoposide on human tumour cells. 1724 62


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