UMLS:C0376358 - FACTA Search

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Query: UMLS:C0376358 (prostate cancer)
59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inhibitory effects of sustained delivery systems (microcapsules) of the modern antagonist of luteinizing hormone-releasing hormone [Ac-D-Nal(2)1, D-Phe(4Cl)2, D-Pal(3)3, D-Cit6, D-Ala10]LH-RH (SB-75) or the potent somatostatin analog D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) were investigated in the Dunning R-3327H rat prostate cancer model. In the first experiment, the treatment was started 4 months after tumor transplantation, when the tumors measured approximately 2 cm3. Tumor volumes and weights were significantly reduced by SB-75 microcapsules releasing 48 micrograms/day or RC-160 microcapsules releasing 38 micrograms/day given alone, as compared with the control. The combination of these two analogs showed a synergistic effect. In the second experiment, the treatment was started 7 months after tumor transplantation, when the tumors were well developed and measured about 16 cm3. In addition to a significant reduction in volume, weight, and growth rate of tumors, histological signs of tumor regression were found in the groups treated with SB-75 microcapsules releasing 72 micrograms/day given alone or in combination with RC-160 microcapsules releasing 76 micrograms/day, but not with RC-160 alone. No synergistic effect of the combination therapy was found in the second experiment. Serum testosterone levels decreased to undetectable levels and LH levels were also diminished within 2 weeks by administration of SB-75 alone or in combination with RC-160. In both experiments, the weights of testes, ventral prostate, and seminal vesicles were greatly reduced by administration of SB-75 alone or in combination with RC-160. Our results suggest that the combined therapy with microcapsules of SB-75 and RC-160, started soon after the diagnosis of prostate cancer is made, could improve therapeutic response.
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PMID:Effect of microcapsules of luteinizing hormone-releasing hormone antagonist SB-75 and somatostatin analog RC-160 on endocrine status and tumor growth in the Dunning R-3327H rat prostate cancer model. 135 72

The effects of treatment with a bombesin receptor antagonist [D-Tpi6, Leu13 psi (CH2NH) Leu14]BN(6-14)(RC-3095) and the combination of an agonist of luteinizing hormone-releasing hormone [D-Trp6]-LH-RH and somatostatin analog D-Phe-Cys-Tyr-D-Trp-Lys-Val- Cys-Trp-NH2 (RC-160) were studied in nude mice bearing xenografts of the hormone-dependent human prostate tumor PC-82. During the 5 weeks of treatment, tumor growth was decreased in all treated groups compared with controls. Bombesin antagonist RC-3095 and the combination of [D-Trp6]-LH-RH and RC-160 caused a greater inhibition of tumor growth than [D-Trp6]-LH-RH or RC-160 alone as based on measurement of tumor volume and percentage change in tumor volume. The largest decrease in tumor weight was also seen in the groups treated with the bombesin antagonist and with the combination of RC-160 and [D-Trp6]-LH-RH. Serum prostatic-specific antigen levels were greatly decreased, and insulin-like growth factor I (IGF-I) as well as growth hormone levels were reduced in all treated groups. Specific binding sites for [D-Trp6]-LH-RH, epidermal growth factor (EGF), IGF-I, and somatostatin (SS-14) were found in the tumor membranes. Receptors for EGF were significantly down-regulated by treatment with the bombesin antagonist or RC-160. Combination of LH-RH agonists with somatostatin analog RC-160 might be considered for improvement of hormonal therapy for prostate cancer. The finding that bombesin antagonist RC-3095 inhibits the growth of PC-82 prostate cancer suggests the merit of further studies to evaluate the possible usefulness of antagonists of bombesin in the management of prostatic carcinoma.
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PMID:Inhibition of growth of PC-82 human prostate cancer line xenografts in nude mice by bombesin antagonist RC-3095 or combination of agonist [D-Trp6]-luteinizing hormone-releasing hormone and somatostatin analog RC-160. 137 10

We followed total prostate and prostatic tumor volumes in patients who received combination endocrine therapy with the antiandrogen flutamide and the LHRH agonist [D-Trp6,des-Gly-NH2(10)]LHRH ethylamide. Twenty-three men with proved prostatic adenocarcinoma (Stages B1 to D2) were subjected to a transrectal ultrasound (TRUS) study before and after a three-month period of combination antihormonal therapy. A total prostatic volume reduction ranging from 17 percent to 70 percent (median 47%, p less than 0.0001) was observed. An even greater effect was observed on tumor volume which was reduced by 20 percent to 91 percent (median 81%, p less than 0.01). After treatment, the original suspicious zone became nonvisible in 4 cases. The TRUS measurements were confirmed by direct examination of the radical prostatectomy specimen in 7 cases. TRUS is thus a precise, sensitive, and valid method for evaluating the effect of combined antihormonal therapy on normal and tumoral prostatic tissues. These data indicate that combination therapy induces a rapid and marked reduction in glandular and tumoral prostatic volume which could well improve the success of radical prostatectomy and increase the changes of cure of localized prostatic cancer.
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PMID:Transrectal ultrasound evaluation of local prostate cancer in patients treated with LHRH agonist and in combination with flutamide. 154 20

The effect of conjugation on the biodistribution of 111In-labelled antibodies was studied in nude mice carrying human prostatic cancer xenografts (PC-82). Two monoclonal antibodies and their fragments raised against human prostate-specific acid phosphatase (PAP) and prostate-specific antigen (PSA) were used. We used the cyclic anhydride of DTPA (CA-DTPA) as a chelating agent, or, alternatively, 1-(p-aminobenzyl)diethylenetriaminepentaacetic acid (NH2-Bz-DTPA) was attached as a linker to the carbohydrate components of the parent molecules. The conjugation method, the amount of circulating antigen and the size of the antibody component affected the blood clearance of the labelled derivatives. F(ab')2 fragments displayed a faster blood clearance than the corresponding derivatives of intact IgG1s. Aminobenzyl derivatives of anti-PAP-IgG1 showed a faster blood clearance than the corresponding CA-DTPA derivatives, but, in the case of derivatives of anti-PSA-IgG1, this was less clear, possibly due to the high PSA concentrations in the mouse sera. All the derivatives studied accumulated in the liver independently of the size of the antibody derivative, most probably due to the formation of antigen-antibody complexes. All CA-DTPA derivatives showed a higher kidney accumulation than the corresponding aminobenzyl derivatives. CA-DTPA-anti-PAP-F(ab')2 fragments showed a higher kidney uptake than the corresponding anti-PSA-F(ab')2 derivatives, since a large fraction of the latter are complexed with circulating antigen, thereby slowing down its reabsorption by the kidney. In addition, the lower kidney accumulation for anti-PSA-F(ab')2 fragments might be, at least partly, due to the electronegative charge of the molecule.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of conjugation on the biodistribution of 111In-labelled anti-PAP and anti-PSA monoclonal antibodies examined in nude mice with PC-82 human tumor xenografts. 172 16

Many clinical approaches for the treatment of hormone-sensitive tumors are being developed based on analogs of LH-RH and somatostatin. Inhibition of the pituitary-gonadal axis forms the basis for oncological applications of LH-RH agonists like [D-Trp6]-LH-RH and new LH-RH antagonists free of edematogenic effects such as [Ac-D-Nal(2)1-D-Phe(4Cl)2-D-Pal(3)3,D-Cit6,D-Ala10]-LH -RH (SB-75). Agonists and antagonists of LH-RH have been used in patients with prostate cancer and might be also beneficial for the treatment of breast cancer and ovarian, endometrial and pancreatic carcinomas. Some of the effects of LH-RH analogs can be due to direct action since LH-RH receptors have been found in these cancers. The use of sustained delivery systems based on microcapsules of PLG, makes the treatment more efficacious. Octapeptide analogs of somatostatin such as D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) and related analogs were designed specifically for antitumor activity. These somatostatin analogs, by virtue of having a wide spectrum of activities appear to inhibit various tumors through multiple mechanisms. Direct antiproliferative actions of somatostatin analogs appear to be mediated by specific receptors located on tumor cells. High affinity binding sites for RC-160 and related analogs have been found in human pancreatic, prostate, breast and ovarian cancers and brain tumors such as meningiomas. In vivo administration of analog RC-160 inhibits the growth of Dunning R-3327 prostate cancers in rats, MXT mammary tumors in mice and BOP-induced ductal pancreatic cancers in hamsters. Combination of microcapsules of RC-160 with [D-Trp6]-LH-RH results in synergistic potentiation of the inhibition of these cancers. Somatostatin analog RC-160 and LH-RH antagonist SB-75 are the object of further experimental studies and clinical trials aimed at the exploration of their inhibitory effects on the processes of malignant growth.
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PMID:Antitumor effects of analogs of LH-RH and somatostatin: experimental and clinical studies. 198 Oct 9

A peptide mitogen for cultured osteoblast-like cells was purified from serum-free conditioned culture medium of a human prostatic cancer cell line, PC-3. Based on amino acid sequencing and estimated molecular weight, this peptide was identified as an NH2-terminal fragment of urokinase-type plasminogen activator (uPA). Recombinant high molecular weight (HMW) uPA and the NH2-terminal growth factor domain (GFD) of uPA, but not low molecular weight (LMW) uPA (lacking the NH2-terminal region) stimulated [3H] thymidine incorporation and proliferation in osteoblast-like cells, and specific, competitive binding sites for HMW, but not LMW, uPA were demonstrable. These studies demonstrate the production of a mitogenic NH2-terminal fragment of uPA by a human prostatic cancer cell line which may be of importance in the pathogenesis of osteoblastic metastases.
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PMID:An amino-terminal fragment of urokinase isolated from a prostate cancer cell line (PC-3) is mitogenic for osteoblast-like cells. 212 13

Three hundred and sixty-three patients with clinical stage D2 prostate cancer who had not received previous endocrine therapy or chemotherapy were treated with the combination therapy using the pure antiandrogen Flutamide and the LHRH agonist [D-Trp6,des-Gly-NH2(10)]LHRH ethylamide (or orchiectomy) for an average of 771 days (24-2607 days). Only 31 of the 308 evaluable patients (10.1%) did not show an objective positive response at the start of the combination therapy compared with an average of 18% in five recent studies using monotherapy. The median survival achieved using monotherapy is approximately 24 months while, in the present study, it is increased to 41.2 months, thus giving an additional 17 months of survival with the combination therapy. It should be mentioned that at the time of relapse, combination therapy is continued and, in addition, further blockade of adrenal androgen secretion is achieved with aminoglutethimide and hydrocortisone. While our studies showing the advantages of combination therapy with pure antiandrogen in advanced prostate cancer have been confirmed by independent large-scale randomized studies, our preliminary data clearly suggest the interest of downstaging early stage prostate cancer by temporary combination therapy prior to radical prostatectomy.
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PMID:Combination therapy with flutamide and medical (LHRH agonist) or surgical castration in advanced prostate cancer: 7-year clinical experience. 228 8

In this study we examined optimization of derivatization of monoclonal antibodies and their fragments intended for use as radiopharmaceutical in radioimaging and/or radioimmunotherapy of prostatic cancer. Two different principles were used to conjugate diethylenetriaminepentaacetic acid (DTPA) to a monoclonal antibody (Mab, subclass IgG1) raised against human prostatic acid phosphatase (PAP). In addition, the F(ab')2 fragments of this Mab were also derivatized. We used the cyclic anhydride of DTPA (CA-DTPA) as a chelating agent for these two protein moieties. Furthermore, the Mab and the F(ab')2 fragments were modified site-specifically by attaching linkers, N-(p-aminobenzyl)diethylenetriaminetetraacetic acid (p-NH2-Bz-DTTA) and 1-(p-aminobenzyl)diethylenetriaminepentaacetic acid (p-NH2-Bz-DTPA), to the carbohydrate components of the parent molecules. In this study, biodistribution of the 111In-labelled derivatives was investigated in normal mice. All the derivatives of IgG1 demonstrated a slower blood clearance than the corresponding derivatives of the F(ab')2 fragments. This property was particularly pronounced in the site-specifically conjugated derivatives of IgG1. All the derivatives studied accumulated in the liver, kidney, and spleen. The CA-DTPA derivatives of F(ab')2 fragments showed the highest kidney-to-blood ratios of radioactivity compared with the other compounds studied. The derivatives of IgG1 showed a higher percentage of the injected dose in liver and spleen tissues than the derivatives of the F(ab')2 fragments. The F(ab')2 fragments studied also gave rise to site-specific derivatives, which demonstrated that carbohydrates were also present in this part of the molecule. They behaved similarly to the CA-DTPA F(ab')2 derivative in other respects, but the kidney accumulation was lower at 72 and 120 h.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biodistribution in normal mice of an 111In-labelled prostatic acid phosphatase-specific antibody and its F(ab')2 fragments derivatized site-specifically or via bicyclic diethylenetriaminepentaacetic acid anhydride. 238

Analogs of a potent octapeptide analog of somatostatin (SRIF) H-(D)Phe-Cys-Tyr-(D)Trp-Lys-Val-Cys-Thr(NH2) were synthesized. Aromatic substitutions for Tyr resulted in little change in inhibitory potency on growth hormone (GH) secretion in the rat. Substitutions for Val or (D)Trp resulted in analogs with diminished activity. Substitution of (D)Nal for (D)Phe increased duration of GH inhibition. Final weights of subcutaneously implanted prostate tumors (R3327) were 41% lower in rats treated with an N-terminal 4-chloro-(D)phenylalanyl analog as compared to vehicle treated controls. The analog had no effect on testicular weight or final plasma testosterone levels. SRIF analogs may represent an alternative treatment for prostate cancer that would be free of the untoward reproductive effects of other treatments (e.g. LH-RH or castration).
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PMID:Inhibition of rat prostate tumor growth by an octapeptide analog of somatostatin. 288 1

The combination of a long-acting delivery system for the agonist [D-Trp6]luteinizing hormone-releasing hormone ([D-Trp6]LH-RH) with modern somatostatin analogs was studied in the Dunning R-3327H rat prostate cancer model. Microcapsules of [D-Trp6]LH-RH releasing 25 micrograms/day were injected once a month. In the first experiment the adjunct was the somatostatin analog D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121), administered at a dose of 2.5 micrograms twice a day, and the therapy was continued for 70 days. Tumor volume was significantly decreased by [D-Trp6]LH-RH microcapsules or RC-121 given alone. The combination of microcapsules and analog RC-121 caused a greater inhibition of tumor growth than the single agents. Similar effects were seen when the percent increase in the tumor volume was examined. The inhibition of tumor growth caused by the [D-Trp6]LH-RH microcapsules was greater than that caused by RC-121. The combination of the two agents was again the most effective, resulting in the smallest increase in tumor volume. Tumor weights were much lower in the groups treated with microcapsules or RC-121 alone than in controls. The lowest tumor weights were obtained in the group that received the combination of [D-Trp6]LH-RH microcapsules and RC-121. Similar results were obtained in the second experiment, in which the animals were treated for a period of 83 days with microcapsules containing the somatostatin analog D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) that released 5 micrograms/day and were injected twice a month alone or in combination with microcapsules of [D-Trp6]LH-RH. Microcapsules of analog RC-160 given alone significantly decreased tumor growth as measured by the final tumor volume, the percentage change from the initial tumor volume, and the reduction in tumor weight. The inhibition of tumor growth induced by [D-Trp6]LH-RH microcapsules was greater than that caused by RC-160. The most striking decrease in tumor weight and volume was obtained in animals treated with microcapsules of [D-Trp6]LH-RH combined with the delayed delivery system for RC-160. The overall response to the combination therapy could reflect the inhibition by somatostatin analogs of the proliferation of prostate cancer cells through a decrease in growth hormone and prolactin release and interference with endogenous growth factors, in addition to the main effect, which is the suppression by [D-Trp6]LH-RH of the growth of androgen-dependent tumor cells. Our results indicate that somatostatin analogs enhance the inhibitory effects of [D-Trp6]LH-RH on the growth of prostate tumors. The administration of somatostatin analogs in combination with microcapsules of [D-Trp6]LH-RH might improve clinical response in patients with advanced prostate carcinoma.
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PMID:Somatostatin analogs as adjuncts to agonists of luteinizing hormone-releasing hormone in the treatment of experimental prostate cancer. 289 Jan 64

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