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)

Twelve patients with stage D2 adenocarcinoma of the prostate were treated with the combination chemotherapy of ifosfamide (2 g/body, i.v., day 1-3), 5-fluorouracil (250 mg/body, i.v., day 1-5) and cisplatin (20-30 mg/body, i.v., day 1-5). The averaged age was 62 years (from 52 to 73 years) with mean performance status of 70% (from 40 to 90%). Six patients were refractory to prior hormone therapy or chemotherapy and the other six had received no prior treatment for prostatic cancer. Based on criteria of National Prostatic Cancer Project, 4 patients achieved partial response (PR) which was maintained from 11 to 23 months with the mean of 17.8 months. Two patients achieved objectively stable stage (NC). Response rate (PR + NC) was 50%. Response rate of patients without prior therapy was 80%, whereas that of hormone-resistant group was 30%. There was a trend toward unfavorable response in patients with prior therapy. Adverse effects were mild to moderate gastric problems and myelosuppression except in one case Adverse effects were mild to moderate gastric problems and myelosuppression except in one case with low performance status under 60%. IFP combination chemotherapy achieved favorable responses and toxicities were tolerable. Therefore, it appears worth while to study whether IFP combination chemotherapy could extend the life of patients with advanced prostatic cancer.
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PMID:[Combination chemotherapy with ifosfamide, 5-fluorouracil, cisplatin for stage D2 prostatic cancer]. 281 18

Estracyt (estramustine phosphate) is a nitrogen mustard derivative of estradiol-17 beta which is rapidly dephosphorylated to yield estramustine. Estramustine is metabolized to estromustine mainly in the liver. Both estramustine and estromustine are retained in rat prostate with a high degree of specificity. This retention is due to the binding of estramustine and/or estromustine to a protein called EMBP (estramustine binding protein). When estimated by HPLC, the molecular weights of these estramustine binding components in rat prostate are 45,000-50,000 and 25,000-30,000, respectively. HPLC and glycerol density gradient analysis clearly demonstrated the occurrence of EMBP in a cytosol preparation from human prostatic cancer tissue. When estimated by HPLC, the molecular weights of estramustine binding components are 45,000 and 25,000 daltons, respectively. In addition, results of effectiveness of Estracyt studied under a cooperative research group in Japan, are reported in this paper. Effectiveness was evaluated at 3 months of the treatment on 121 patients with untreated prostatic cancer (Study I) and 95 patients with reactivated cancer (Study II), at 12 months of the treatment on 68 patients in Study I and 85 patients in Study II, and at 24 months on 37 patients in Study I and 23 patients in Study II. At 3 months of the treatment, Estracyt was effective in 89% of untreated prostatic cancers, and 38% of reactivated prostatic cancers. At 24 months of the treatment, this drug was effective in 65% of untreated prostatic cancers and 30% of reactivated ones. Estracyt is especially recommended as a first-choice drug for both the untreated patients with poorly differentiated adenocarcinoma and reactivated cancer.
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PMID:[Estracyt (estradiol-nitrogen mustard complex)--estramustine binding protein and its specificity]. 648 30

We report a 55-year-old man with papilledema and multiple cranial nerve palsies. He was well until 52 years of age when there was an onset of progressive difficulty in initiating urination; he visited the urology service of our hospital where a diagnosis of prostate cancer was made; the cancer was invading the bladder and was metastasizing to lymph nodes and bones. He was treated with oochiectomy and estrogen preparations with some improvement in his symptoms. Two years later, he developed difficulty in urination again, and transurethral resection of the tumor was performed in 1991. In December 1991, he noted tingling and numb sensation in his left face, which had become progressive worse within the next one month, and he developed blepharoptosis and deafness all on the left side. He was admitted to the urology service on February 4, 1992, and a neurological consultation was asked. On physical examination, general findings were unremarkable, except for lymph node enlargements of about 0.5 to 1.0 mm in size in cervical and inguinal regions. On neurologic examination, he was alert with normal mental activities; higher cerebral functions were intact. He had normal vision and visual fields, however, papilledema was present bilaterally; pupils and light reactions were normal. Extraocular muscles were intact on the right side, however, moderate restriction was noted in the left eye in that all the extraocular muscles except for the medial rectus were weak; blepharoptosis was noted on the left; no nystagmus was present. The sensation was diminished in the left face, and left facial paresis of the peripheral type was also noted; the taste sensation was also diminished in the left anterior two thirds of the tongue. He had sensorineural deafness on the left side. The other cranial nerves appeared intact. He walked normally; no weakness or muscle atrophy was noted; muscle tone was normal and no ataxia was observed. Deep reflexes were normally elicited and symmetric; the plantar response was flexor. No meningeal signs were present. Laboratory examination revealed following abnormalities: Hb 7.1 g/dl, platelet 47,000/cmm, WBC3,800/cmm, LDH 950IU/l, PAP232ng/ml (normal less than 1.6), PA2.631ng/ml (normal less than 7.4); a small amount of effusion was noted in the left pleural cavity; cytological examination of the fluid was class V. A cranial CT scan as well as MRI were entirely normal, as was the spinal tap. He was treated with glycerol, however, there was progressive increase in the pleural effusion, and he developed dyspnea; moist rale had become audible in the end of February.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[A 55-year-old man with prostate cancer, papilledema, and multiple cranial nerve palsies]. 794 37

The pattern of chromosomal aberrations and their significance in prostate cancer are poorly understood. We studied 23 prostate cancer and 10 benign prostatic hyperplasia (BPH) specimens by fluorescence in situ hybridization (FISH) using pericentromeric repeat-specific probes for 10 different chromosomes. The aims of the study were: 1) to compare the sensitivity of FISH and DNA flow cytometry in aneuploidy detection, 2) to determine which chromosome copy number changes are most common, and 3) which probe combinations would be most effective in aneuploidy diagnosis. Disaggregated tumor cells from formalin-fixed, paraffin-embedded tissues were pretreated with our newly developed method based on hot glycerol solution to improve probe penetration. All BPH specimens were diploid by DNA flow cytometry and showed no numerical chromosome aberrations by FISH. In prostate cancer, flow cytometry showed abnormal DNA content in 35% of cases, whereas 74% were abnormal by FISH. Aberrant copy number of chromosomes 8 (48% of cases), X (43% of cases), and 7 (39% of cases) were most common. Ninety-four percent of all aneuploid cases would have been detected with these three probes alone. Simple chromosome losses were uncommon but in DNA tetraploid tumors relative losses (trisomy or disomy) of several chromosomes were often found, suggesting progression of prostate cancer through tetraploidization followed by losses of selected chromosomes. In conclusion, our results indicate that FISH using three selected chromosome-specific probes is two to three times more sensitive than flow cytometric DNA content analysis in aneuploidy detection.
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PMID:Sensitive detection of chromosome copy number aberrations in prostate cancer by fluorescence in situ hybridization. 808 44

The serine proteinase prostate-specific antigen (PSA), and its complex with the serine proteinase inhibitor alpha(1)-antichymotrypsin (ACT), have been used as markers for the diagnosis of prostate cancer. PSA prepared from seminal fluid is typically contaminated with the trypsin-like glandular kallikrein (hK2). Here we describe a convenient and reproducible preparation of catalytically active recombinant PSA (rPSA) and demonstrate an overall similarity in the properties of cloned and refolded rPSA to PSA purified from seminal fluid. We also present results that are relevant for increasing the sensitivity of assays of PSA activity in biological fluids, for the putative role of PSA activity in physiologically important processes, including prostate cancer metastasis, and for the design of PSA inhibitors. Specifically, we find that added salts, in particular NaCl, give rise to dramatic increases in rPSA catalytic activity, as does added glycerol. On the other hand, Zn(2+), spermine, and spermidine, each a major component of seminal and prostatic fluid, strongly inhibit rPSA activity, with Zn(2+) being a non-competitive inhibitor while spermine is a competitive inhibitor. Citrate, also a major component of seminal and prostatic fluid, spermine, and spermidine each protect rPSA from Zn(2+) inhibition, presumably via Zn(2+) sequestration. Finally, rPSA efficiently proteolyzes several protein substrates.
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PMID:The preparation and catalytic properties of recombinant human prostate-specific antigen (rPSA). 1096 94

The ability of the naturally occurring ether lipid, 1-O (2 methoxy) hexadecyl glycerol (MHG), and phenylbutyrate (BP) to inhibit cellular proliferation, anchorage-independent growth and cellular invasion in the human prostate cancer LnCap and DU145 cells was determined. Both MHG and PB inhibited the malignant properties of these prostate cancer cells. The concentrations required to achieve similar inhibitory effect, however, were significantly different for these two agents. MHG inhibited cell growth with equal potency in these cell lines with an IC-50 value of 93 microM for LnCap, and 97 microM for DU145. The IC-50 values for PB were 1.3 mM and 7.3 mM, respectively, for LnCap and DU145 cells. Both MHG and PB (IC-50 concentrations) inhibited the anchorage-independent growth and cellular invasion in these cells. Over 50% inhibition of anchorage-independent growth was achieved for both LnCap and DU145 cells by PB, while a lesser degree of inhibition was achieved with MHG. Both MHG- and PB-treated cells showed a reduced propensity to invade matrigels. Invasion of PB-treated LnCap and DU145 cells was reduced, respectively, by approximate 41 and 30% when compared to untreated control cells, while invasion of MHG-treated LnCap and DU145 cells was reduced to a lesser extent. Because differentiation-inducing agents may possess chemopreventive properties, the use of naturally occurring MHG and nontoxic PB in the chemoprevention of malignant diseases warrants further investigation.
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PMID:Inhibitory effect of 1-O (2 methoxy) hexadecyl glycerol and phenylbutyrate on the malignant properties of human prostate cancer cells. 1144 61

Phorbol esters, the archetypical (PKC) activators, induce apoptosis in androgen-sensitive LNCaP prostate cancer cells. In this study we evaluate the effect of a novel class of PKC ligands, the diacylglycerol (DAG)-lactones, as inducers of apoptosis in LNCaP cells. These unique ligands were designed using novel pharmacophore- and receptor-guided approaches to achieve highly potent DAG surrogates. Two of these compounds, HK434 and HK654, induced apoptosis in LNCaP cells with much higher potency than oleoyl-acetyl-glycerol or phorbol 12,13-dibutyrate. Moreover, different PKC isozymes were found to mediate the apoptotic effect of phorbol 12-myristate 13-acetate (PMA) and HK654 in LNCaP cells. Using PKC inhibitors and dominant negative PKC isoforms, we found that both PKCalpha and PKCdelta mediated the apoptotic effect of PMA, whereas only PKCalpha was involved in the effect of the DAG-lactone. The PKCalpha selectivity of HK654 in LNCaP cells contrasts with similar potencies in vitro for binding and activation of PKCalpha and PKCdelta. Consistent with the differences in isoform dependence in intact cells, PMA and HK654 show marked differences in their abilities to translocate PKC isozymes. Both PMA and HK654 induce a marked redistribution of PKCalpha to the plasma membrane. On the other hand, unlike PMA, HK654 translocates PKCdelta predominantly to the nuclear membrane. Thus, DAG-lactones have a unique profile of activation of PKC isozymes for inducing apoptosis in LNCaP cells and represent the first example of a selective activator of a classical PKC in cellular models. An attractive hypothesis is that selective activation of PKC isozymes by pharmacological agents in cells can be achieved by differential intracellular targeting of each PKC.
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PMID:Diacylglycerol (DAG)-lactones, a new class of protein kinase C (PKC) agonists, induce apoptosis in LNCaP prostate cancer cells by selective activation of PKCalpha. 1158 14

Tea polyphenols have been proposed as potential chemopreventive agents against prostate cancer, primarily because of their high intake by populations with reduced cancer incidence and their reported ability to inhibit proliferation and increase apoptosis in prostate cancer cells in culture. Insulin-like growth factor-I (IGF-I) has been implicated as a risk factor for the development of prostate cancer by epidemiological studies and has been shown to be causative in animal models. One of the primary signal transduction pathways activated by IGF-I binding to its receptor is the Akt pathway. We determined that phosphorylated Akt levels are very low in serum-starved human normal prostate epithelial cells (PrEC) and Du145 prostate carcinoma cells, and that treatment of these cells with IGF-I results in a rapid and sustained phosphorylation of Akt. Pre-treatment of PrEC and Du145 cells with doses as low as 20 microg/ml of a mixture of black tea polyphenols (BTP) substantially reduced IGF-I-mediated Akt phosphorylation. This effect of BTP appears to be due partially to the reduced autophosphorylation of IGF-I receptor-1 in BTP-treated cells. BTP pre-treatment also decreased downstream effects of Akt activation including phosphorylation of glycerol synthase kinase-3, increased cyclin D1 protein levels and increased DNA synthesis. Our results indicate that polyphenols from black tea inhibit the IGF-I signal transduction pathway, which has been linked to increased prostate cancer incidence in human populations and, therefore, provide further support for the potential of BTP to prevent prostate cancer.
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PMID:Black tea polyphenols inhibit IGF-I-induced signaling through Akt in normal prostate epithelial cells and Du145 prostate carcinoma cells. 1175 45

Four lignanamides, a tyramine derivative, and 10 other nonalkaloidal components were isolated from the seeds of Hyoscyamus niger. Among them, hyoscyamide (1), 1,24-tetracosanediol diferulate (6), and 1-O-(9Z,12Z-octadecadienoyl)-3-O-nonadecanoyl glycerol (7) are new structures. The other compounds were identified as grossamide, cannabisin D, cannabisin G, N-trans-feruloyl tyramine, 1-O-octadecanoyl glycerol, 1-O-(9Z,12Z-octadecadienoyl) glycerol, 1-O-(9Z,12Z-octadecadienoyl)-2-O-(9Z,12Z-octadecadienoyl) glycerol, 1-O-(9Z,12Z-octadecadienoyl)-3-O-(9Z-octadecenoyl) glycerol, rutin, vanillic acid, beta-sitosterol, and daucosterol. Grossamide, and cannabisins D and G exhibited moderate cytotoxicity in cultured LNCaP human prostate cancer cells.
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PMID:Lignanamides and nonalkaloidal components of Hyoscyamus niger seeds. 1185 58

In comparison with other OECD countries with good cancer registries, New Zealand has the highest mortality rate of colon cancer, second highest of breast cancer and third highest of prostate cancer. A possible association with heterocyclic amine consumption has been suggested for each of these cancers. Studies of locally cooked meat suggest that the main contributors to heterocyclic amines in the New Zealand diet would be well-cooked beef, chicken and pork. Well-cooked beef steak, and the specific heterocyclic amine, IFP, showed a weak positive correlation with prostate cancer risk in the New Zealand population, but no studies thus far have considered the role of meat cooking practices or heterocyclic amines in the development of other cancers. The Maori and Pacific Island people, despite a superficially similar diet, have a substantially lower incidence of colon cancer than people of Caucasian origin. These differences are particularly intriguing in view of a report that a very high percentage of these people have a fast acetylator phenotype-a factor suggested to augment the effect of well-cooked red meat in other populations. The three population groups are known to differ in their preferences for meat type (including processed meats), and there are anecdotal suggestions that they may differ in preferred cooking methods. More detailed population studies are warranted to establish the role of meat, meat processing, cooking methods and the interaction with food plants and/or with genotype and phenotype in New Zealand.
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PMID:Meat consumption, cancer risk and population groups within New Zealand. 1235 Nov 61


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