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)

Since the introduction of bone scans in 1951, there have been many studies comparing biologic and physical characteristics of new bone-imaging agents and the results of scintigraphy and radiology in large numbers of patients. Relatively speaking, there have been fewer studies detailing the health benefits and financial cost associated with the use of skeletal scintigraphy. This review concerns these aspects in patients with malignancies of various sites and stages. About 2% of patients with stage I or II breast cancer have bone metastases at the time they first present, whereas nearly 28% of patients with stage III disease have bone metastases. A large percentage of patients with initially negative scans develop bone metastases during the first 3--4 yr; many of them develop them within the first 12--18 mo after initial diagnosis. For patients with lung cancer, the use of bone scans in staging their disease is somewhat controversial. Several studies indicate that the yield of positive bone scans may range from as low as 2% to as high as 35%. Data on the use of bone scans in staging prostatic cancer initially are similar to those in patients with breast cancer, that is, yields of 7% in patients with stage I or II disease and a yield of about 20% with stage III disease. Children with osteosarcoma or Ewing's sarcoma rarely have bone disease distant from the site of their primary bone lesion at presentation. However, a large percentage of them (30%--40% or so) develop bone metastases during the follow-up period. As in the case with patients with breast cancer, about half of these bone metastases are evident by 12--18 mo.
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PMID:Rationale for the use of bone scans in selected metastatic and primary bone tumors. 11 84

Cancer chemotherapy has developed rapidly over the last twenty years. The majority of patients with cancer die from metastatic disease, so the major therapeutic advance now must be better systemic therapy. From its early beginning in the 1940's with oestrogen therapy for prostatic cancer, nitrogen mustards in the lymphomas, and folic acid antagonists in childhood leukaemia, there are now between thirty and forty active anti-cancer agents in clinical use. The main clinical pharmacological points of the major agents are briefly reviewed, together with their main dose-limiting toxic effects and their activity as single agents. Clinical chemotherapy has developed by the introduction of newer agents from the drug screening programmes and a better understanding of the scheduling to avoid serious toxicity. Although drug-resistance is still a major problem, by combining different active agents there has been a dramatic improvement in survival of patients with selected tumours. More recently, treatment of patients early, before they have gross clinical recurrence, has already shown some benefit in pre-menopausal patients with carcinoma of the breast and in patients with osteosarcoma. The limitations of clinical measurements in monitoring therapy are clear, and a major improvement could well be realised if therapy could be monitored on the basis of quantitative markers. The clinical impact of cancer chemotherapy has already been dramatic in drug-sensitive tumours, but these only contribute a small proportion of the total. Some of the common tumours fall into the group that are relatively drug sensitive where the lives of patients can be prolonged, but there is still a significant fraction of tumours which are insensitive to existing drugs and which will probably require the development of newer agents before chemotherapy can make any impact on the survival of patients with these tumours.
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PMID:The current role of cancer chemotherapy. 36 Nov 39

Functional loss of the retinoblastoma (RB) gene has been implicated in the initiation or progression of several human tumor types including cancer of the eye, bone, bladder, and prostate. To examine the consequence of adding one RB allele containing its normal regulatory elements back into representative examples of each of these cancer types, as well as to compare the results to those previously reported using various RB complementary DNA constructs, a neomycin resistant marked 13 chromosome was transferred by microcell fusion. Several attempts to obtain RB positive osteosarcoma cells failed. In addition, only one RB positive retinoblastoma clone was isolated. This clone contained many large cells, could not be maintained in long-term culture, and produced only RB negative tumors. Three RB positive bladder cancer cell clones were obtained, all of which grew slower in culture than their RB negative parental counterpart and did not form colonies in soft agar. Tumorigenicity was markedly suppressed in these clones. One clone yielded no tumors, and the other 2 clones produced only one small tumor each, both of which were RB negative. In contrast, the 2 RB positive prostate cancer cell clones isolated had no differences in their cell culture growth properties, including growth in soft agar compared to the parental cells. One of the clones was nontumorigenic, while the other clone produced 4 small tumors, all of which were RB positive. These results indicate that the transfer of one RB allele by microcell transfer produces different levels of growth inhibition as well as tumor suppression, depending on the cell type examined. In the case of prostate cancer, the function of the RB gene in tumor suppression appears to be independent from its growth regulatory function, since no growth inhibition in cell culture was noted in these cells, although tumor suppression was significant.
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PMID:Changes in growth and tumorigenicity following reconstitution of retinoblastoma gene function in various human cancer cell types by microcell transfer of chromosome 13. 142 76

Bromodeoxyuridine (BrdU) labeled human prostatic cancer cells, PC-3, and murine osteosarcoma cells, POS-1 were injected into the tail veins of male mice under concomitant temporal occlusion of inferior vena cava. Five minutes after release of the venous occlusion, animals were sacrificed and various tissues, organs and the vertebral bones were examined immunohistochemically using an application of BrdU-anti-BrdU methods. Obvious BrdU labeled tumor cells, isolated or clumped, were demonstrated within the venous channels along the vertebral column, the epidural venous channels around spinal nervous tissues, in the bone marrow of lumbo-sacral vertebrae and intra- and peri-prostatic venous channels. The results suggest that a blockade of short duration of venous flow at the inferior vena cava can result in the bypassing of tumor cells through the vena cava to the vertebral venous system, which has a close connection with the peri-prostatic venous plexus. Thus, the vertebral venous system may play an important role in the metastasis of prostatic carcinoma to bone. In addition this experimental procedure is a very valuable model for studying mechanisms and prevention of bone metastases from prostatic carcinoma.
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PMID:Role of the vertebral venous system in metastatic spread of cancer cells to the bone. 149 28

Based on the clinical evaluations about over 1800 patients who had been treated with fast neutrons at NIRS, the radiobiological properties of high LET radiations were discussed. The most favorable clinical results by fast neutron treatment had been revealed in such diseases as follows; salivary gland tumors, prostate cancer, Pancoast type lung cancer, osteosarcoma, soft tissue sarcoma. The characteristics of these tumors as to the radiobiological properties and the dose distribution are, 1) relatively slow growing tumors and higher RBE for tumor tissue, and 2) capability of correct delivery of a big radiation doses to the target, without any severe radiation complications. Normal tissue tolerance (NSD formulas) for each tissues were also discussed.
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PMID:[Normal tissue tolerance to high LET radiotherapy]. 212 4

Prostatic cancer is frequently associated with new bone formation although the tumor-derived factors responsible for changes in bone cell function have not been identified. We have examined the synthesis of osteoblast-stimulating factors in a cultured human prostatic cancer cell line (PC-3) and show that conditioned medium from PC-3 cells stimulate mitogenesis and alkaline phosphatase in cells with the osteoblast phenotype (cultured rat osteosarcoma cells) and collagen synthesis in fetal rat calvaria. In order to characterize tumor-derived gene products which stimulate cells of the osteoblast phenotype messenger RNA (mRNA) was isolated from PC-3 cells and microinjected into Xenopus laevis oocytes. mRNA-directed translation products which were secreted into the oocyte medium were collected and assayed for a number of osteoblast stimulating properties. Translation products from PC-3 mRNA-injected oocytes stimulated division of cultured osteosarcoma cells by 8-fold and increased DNA synthesis as measured by incorporation of [3H]thymidine into these cells. In addition, tumor-derived translation products stimulated the production of alkaline phosphatase activity, a marker enzyme for bone formation, in cultured osteosarcoma cells. Oocytes injected either with water or with mRNA from a tumor not associated with bone formation were devoid of these activities. Total mRNA from the human prostatic cancer cells was then denatured and fractionated by size by agarose gel electrophoresis. When individual fractions of mRNA were eluted from the gel, translated in Xenopus oocytes, and the secreted translation products were tested for alkaline phosphatase-stimulating activity on osteoblast-like cells, the majority of the activity could be recovered in a mRNA fraction which was approximately 1800 bases in length. These results indicate that the PC-3 prostatic cancer cell line synthesizes a mRNA of approximately 1800 bases which codes for a heretofore unrecognized osteoblast-stimulating factor.
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PMID:Identification of a messenger ribonucleic acid fraction in human prostatic cancer cells coding for a novel osteoblast-stimulating factor. 386 13

Skeletal metastases from prostate cancer is common and usually do not pose a diagnostic dilemma. This study reviews radiographic appearances of prostatic metastases to the appendicular skeleton in four patients where the appearances simulated osteosarcoma, Paget's disease and Paget's sarcoma. Prostatic metastases to long bones can produce appearances considered characteristic of other lesions and suggest misleading alternative diagnoses.
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PMID:Appendicular metastatic prostate cancer simulating osteosarcoma, Paget's disease, and Paget's sarcoma. 748 3

Elucidating the relevant genomic changes mediating development and evolution of prostate cancer is paramount for effective diagnosis and therapy. A putative dominant-acting nude mouse prostatic carcinoma tumor-inducing gene, PTI-1, has been cloned that is expressed in patient-derived human prostatic carcinomas but not in benign prostatic hypertrophy or normal prostate tissue. PTI-1 was detected by cotransfecting human prostate carcinoma DNA into CREF-Trans 6 cells, inducing tumors in nude mice, and isolating genes displaying increased expression in tumor-derived cells by using differential RNA display (DD). Screening a human prostatic carcinoma (LNCaP) cDNA library with a 214-bp DNA fragment found by DD permitted the cloning of a full-length 2.0-kb PTI-1 cDNA. Sequence analysis indicates that PTI-1 is a gene containing a 630-bp 5' sequence and a 3' sequence homologous to a truncated and mutated form of human elongation factor 1 alpha. In vitro translation demonstrates that the PTI-1 cDNA encodes a predominant approximately 46-kDa protein. Probing Northern blots with a DNA fragment corresponding to the 5' region of PTI-1 identifies multiple PTI-1 transcripts in RNAs from human carcinoma cell lines derived from the prostate, lung, breast, and colon. In contrast, PTI-1 RNA is not detected in human melanoma, neuroblastoma, osteosarcoma, normal cerebellum, or glioblastoma multiforme cell lines. By using a pair of primers recognizing a 280-bp region within the 630-bp 5' PTI-1 sequence, reverse transcription-PCR detects PTI-1 expression in patient-derived prostate carcinomas but not in normal prostate or benign hypertrophic prostate tissue. In contrast, reverse transcription-PCR detects prostate-specific antigen expression in all of the prostate tissues. These results indicate that PTI-1 may be a member of a class of oncogenes that could affect protein translation and contribute to carcinoma development in human prostate and other tissues. The approaches used, rapid expression cloning with the CREF-Trans 6 system and the DD strategy, should prove widely applicable for identifying and cloning additional human oncogenes.
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PMID:Identification of the human prostatic carcinoma oncogene PTI-1 by rapid expression cloning and differential RNA display. 754 76

Stromal-epithelial interaction has a fundamental role in determining normal prostate development. Aberrant interaction between stroma and epithelium in the prostate is thought to contribute to neoplastic progression. Using a cell-cell interaction model, we observed that an inductive fibroblast cell line derived from fetal urogenital sinuses can confer growth responsiveness to androgen in both prostate and non-prostate epithelial cells in vivo. This concept was applied to test whether inductive stromal cells from bone or prostate alter cancer growth and metastasis. We observed that when a non-tumorigenic stromal cell line derived from a human osteosarcoma interacted with a non-tumorigenic androgen dependent prostate cancer cell line (LNCaP) in vivo, there was a marked alteration of both genotypes and phenotypes of the subsequently derived LNCaP sublines. One such subline, C4-2, acquired androgen independence as well as osseous-metastatic potential. These results support the concept that "genomic adaptation" is the most likely mechanism to explain the phenomenon of prostate cancer cell lines being permanently altered as a result of stromal-epithelial interaction in vivo. The establishment and further refinement of this cell-cell interaction model will allow us to define the roles of growth factors, growth factor receptors and extracellular matrices in prostate carcinogenesis. This approach could lead to the development of new therapeutic modalities that influence the rate of human prostate cancer progression.
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PMID:The role of stromal-epithelial interaction in normal and malignant growth. 762 72

The transplantation of PA-III rat prostate cancer cells onto rat skeleton produces osteoblastic metastases. Therefore w e studied the paracrine interactions between the PA-III cells and osteoblast-derived osteosarcoma cells (UMR 106 cells). A serine protease secreted by PA-III cells hydrolyzed IGF-binding protein-1 and IGF-binding protein-2 (IGFBP-1 and IGFBP-2) detected in the cell culture media (CM) of OMR 106 cells by western ligand blotting. The serine protease of PA-III cell CM was purified using a benzamidine affinity column. This protease was a protein of 45-50 kDa on polyacrylamide gel electrophoresis under non-reducing conditions but generated two protein bands under reducing conditions; a) one of 33-35 kDa possessing protease activity and b) another of 20-25 kDa which was proteinolytically inactive. Sequence analysis identified the amino acid sequence of the a-chain (20-25 kDa band) and of the b-chain (33-35 kDa band) of rat urokinase-type plasminogen activator molecule. Urokinase purified from PA-III cell CM hydrolyzed IGFBPs of UMR 106 cells and stimulated the proliferation of UMR 106 cells in serum-free cultures. Its protease activity was abolished by benzamidine and aprotinin. Its mitogenic activity for osteoblasts was inhibited by anti-IGF-I monoclonal antibody. Northern blot analysis documented the expression of the urokinase-type plasminogen activator gene in the mRNA extracted from PA-III cells. Urokinase expression was inhibited by dexamethasone. Therefore, we conclude that urokinase-type plasminogen activator stimulates osteoblasts via an IGF-I dependent mechanism. Hydrolysis of the IGFBOPs at the sites of PA-III cell-induced bone tumors account for an increased bioavailability of IGFs. This may facilitate the development and the growth of PA-III cell-induced bone tumor and can also mediate the subsequent local osteoblastic reaction.
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PMID:Urokinase-type plasminogen activator: a paracrine factor regulating the bioavailability of IGFs in PA-III cell-induced osteoblastic metastases. 768 89


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