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排序方式: 共有920条查询结果,搜索用时 31 毫秒
91.
Cytotoxic luteinizing hormone-releasing hormone (LH-RH) analogs, AJ-004 (agonist [D-Lys6]LH-RH linked to methotrexate (MTX)), T-98 ([D-Lys6]LH-RH coupled to glutaryl-2-(hydroxymethyl)anthraquinone) (G-HMAQ) and T-121/B (antagonist containing two residues of G-HMAQ) were tested in female BDF1 mice bearing MXT ((3.2)/Ovex) estrogen-independent mammary tumors. All three cytotoxic LH-RH analogs, administered from Alzet Osmotic Minipumps for 3 weeks, produced a significant inhibition of tumor growth. The effects of T-98 and T-121/B were superior to those obtained by treatment with equimolar doses of cytotoxic moiety anthraquinone or the LH-RH carrier alone. We assume that cytotoxic LH-RH analogs have a combined hormonal and cytotoxic activity with a reduced toxicity after administration in vivo. This is the first demonstration of in vivo tumor inhibition by targeted LH-RH analogs bearing cytotoxic radicals. 相似文献
92.
P M Girard E Goldschmidt D Vittecoq P Massip J Gastiaburu M C Meyohas J P Coulaud A V Schally 《AIDS (London, England)》1992,6(7):715-718
OBJECTIVE: To evaluate the efficacy and tolerance of vapreotide, a new somatostatin analogue, in the treatment of refractory AIDS-related diarrhoea. DESIGN: An open, non-comparative pilot trial. SETTING: The trial was conducted in 10 medical centres in France. PATIENTS, PARTICIPANTS: Thirty-four AIDS patients with chronic diarrhoea unresponsive to conventional antidiarrhoeal therapy were enrolled. Cryptosporidiosis was diagnosed in 21 out of 30 evaluable patients. Mean number of stools prior to therapy was 10.1 +/- 4.9 per day (range, 3-20 stools per day). INTERVENTION: After initial baseline studies, patients received subcutaneous vapreotide at escalating doses of 400 (23 patients) or 500 micrograms (seven patients), between two and six times daily. MAIN OUTCOME MEASURES: Efficacy was assessed after 14 days of therapy, when it was found to be effective. Responders were offered the opportunity to continue receiving therapy. RESULTS: Four patients demonstrated a complete response and 12 a partial response with greater than 50% reduction in daily stool emission. Fourteen patients did not respond to doses up to 2400 micrograms/day. Patients with conditions other than cryptosporidiosis had a significantly higher probability of response (P = 0.013), as did those with milder diarrhoea (less than 10 stools per day). Median duration of response was 1.5 months (range, 0.5-5 months); relapse occurred in five out of eight responders despite maintenance therapy. Toxicity was minimal. CONCLUSIONS: We conclude that AIDS patients with diarrhoea not caused by Cryptosporidium may benefit from vapreotide therapy. 相似文献
93.
G Srkalovic R Z Cai A V Schally 《The Journal of clinical endocrinology and metabolism》1990,70(3):661-669
The binding characteristics of several somatostatin (SS-14) analogs developed in our laboratory were examined in various human and animal tumors and normal tissues. In rat cerebral cortex and human breast cancer membranes the interaction of SS-14 with its binding sites was rapid, specific, saturable, linear with protein concentrations, and dependent on time and temperature. Analysis of kinetic and equilibrium experimental data showed that the interaction of [125I-Tyr11]SS-14 with the binding sites in all normal and tumoral tissue specimens was consistent with the presence of a single class of noncooperative binding sites. Superactive octapeptide analogs of somatostatin-containing hexapeptide sequences Cys-Phe-D-Trp-Lys-Thr-Cys or Cys-Tyr-D-Trp-Lys-Val-Cys showed significant binding affinities to SS-14 receptors. Among these analogs, D-Trp-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2 (RC-98-I) showed the highest binding affinity to normal human pancreatic tissue and human pancreatic adenocarcinoma. In contrast, Sandostatin (SMS 201-995) bound only to normal pancreas, not to human pancreatic cancers. Analog RC-98-I also showed a high binding to human and rat prostate cancers. In human epithelial ovarian cancers and an arrhenoblastoma, analogs D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Trp-NH2 (RC-95-I), D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121) and D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) appeared to be the most potent in displacing labeled SS-14. Analogs Ac-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2 (RC-101-I) as well as RC-121, RC-160, and RC-95-I, but not SMS-201-995, showed high binding affinity in human breast cancers. In specimens of human meningioma the highest binding was found with analogs RC-121, RC-95-I, and RC-101-I. Since marked variations in binding affinities were noted for several analogs in the tissues of origin and the tumors, this suggest that differences may exist between somatostatin receptors not only in normal vs. cancerous tissues, but also among various tumors. Our findings also imply that some analogs could be therapeutically superior to others in the treatment of certain tumors. 相似文献
94.
95.
Ioulia Chatzistamou Andrew V. Schally Jozsef L. Varga Kate Groot Patricia Armatis Ana Bajo 《Journal of cancer research and clinical oncology》2001,127(11):645-652
PURPOSE: To evaluate the tumor inhibitory activities of antagonists of growth hormone-releasing hormone (GH-RH) and vasoactive intestinal peptide (VIP) in UCI-107 human ovarian cancer model, and to investigate the role of the insulin-like growth factor (IGF) system in the response. METHODS: In the present study we investigated the effects of GH-RH antagonist JV-1-36 and VIP antagonist JV-1-52, on the growth and tumorigenicity of UCI-107 ovarian cell carcinoma xenografted into nude mice. Studies on the effects of hGH-RH(1-29)NH2, IGF-I, IGF-II, JV-1-36, and JV-1-52 on the proliferation of UCI-107 cells cultured in vitro were also performed. RESULTS: After 22 days of therapy with JV-1-36 or JV-1-52 at the dose of 20 microg/day, the final volume of UCI-107 tumors was significantly (P<0.05) decreased by 50.5% and 56%, respectively, compared to controls. The concentration of IGF-II in tumors was reduced by 66% in the JV-1-36-treated group and by 62% in the group given JV-1-52 (both P < 0.05). Exposure in vitro to 1 microM concentrations of JV-1-36 or JV-1-52 for 24 h decreased the tumorigenicity of UCI-107 cells in nude mice. All ten mice injected with cells treated with medium alone developed tumors within 23 days after cell inoculation, while only eight of ten and four of ten mice injected with cells exposed to JV-1-36 or JV-1-52, respectively, had tumors. In vitro exposure of UCI-107 cells to 5-35 ng/ml IGF-II produced a significant suppression in the rate of cell proliferation (P < 0.01). CONCLUSION: Our results suggest that GH-RH and VIP antagonists inhibit the growth of UCI-107 ovarian cell carcinoma by mechanisms that appear to involve direct effects on the cancer cells. 相似文献
96.
R Z Cai H Reile P Armatis A V Schally 《Proceedings of the National Academy of Sciences of the United States of America》1994,91(26):12664-12668
Various pseudononapeptide bombesin (BN)-(6-14) antagonists with a reduced peptide bond (CH2-NH) between positions 13 and 14 can suppress the mitogenic activity of BN or gastrin-releasing peptide in 3T3 fibroblast cells and small cell lung carcinoma. In the search for more potent BN antagonists, 10 modified nonapeptide BN antagonists containing N-terminal D-Phe, D-Cpa, and D- or L-Tpi and C-terminal Leu-psi(CH2-N)-Tac-NH2, Leu-psi(CH2-N)-MeTac-NH2, or Leu-psi(CH2-N)-Me2Tac-NH2 have been synthesized by incubating [13 psi 14,CH2-NH,Cys14]BN-(6-14) or [13 psi 14-CH2-NH,Pen14]BN-(6-14) with formaldehyde or acetaldehyde (Cpa = 4-chlorophenylalanine, Tac = thiazolidine-4-carboxylic acid, Tpi = 2,3,4,9-tetrahydro-1H- pyrido[3,4-b]indol-3-carboxylic acid, and Pen = penicillamine). The biological activities of these compounds were then evaluated. [D-Phe6,13 psi 14,CH2-N,Tac14]BN-(6-14) (RC-3950-II) and [D-Phe6,13 psi 14,CH2-N,Me2Tac14]BN-(6-14) (RC-3985-II) exhibited greater potency in inhibition of 125I-labeled [Tyr4]BN binding to Swiss 3T3 cells than their parent compounds [D-Phe6,13 psi 14,CH2-NH,Cys14]BN-(6-14) (RC-3950-I) and [D-Phe6,13 psi 14,CH2-NH,Pen14]BN-(6-14) (RC-3985-I). The order of binding affinities of these compounds was as follows: [13 psi 14,CH2-N,Tac14]BN-(6-14) > [13 psi 14,CH2-N,Me2Tac14]BN-(6-14) > [13 psi 14,CH2-N,MeTac14]BN-(6-14). In most cases, the analogs with C-terminal Leu-psi(CH2-N)-Tac-NH2 were also more potent growth inhibitors of 3T3 cells than compounds containing C-terminal Leu-psi(CH2-N)-Me2Tac-NH2 or Leu-psi(CH2-N)-MeTac-NH2. The best BN antagonists of this series, RC-3950-II and [D-Cpa6,13 psi 14,CH2-N,Tac14]BN- (6-14) (RC-3925-II), inhibited gastrin-releasing peptide-stimulated growth of Swiss 3T3 cells with IC50 values of 1 nM and 6 nM, respectively. Since antagonists of this class inhibit growth of various tumors in animal cancer models, some of them may have clinical applications. 相似文献
97.
This case report discusses the unusual presentation and ultrasound features of a solitary fibrous tumour of the face. Solitary fibrous tumour is an uncommon form of soft tissue tumour which, although seen predominantly within the lung pleura, can occur throughout the body in sites such as the peritoneum, mediastinum and head and neck. Ultrasound is an excellent imaging modality in the assessment of soft tissue masses in the head and neck. The ultrasound features demonstrated by this example of solitary fibrous tumour are reviewed. This report also highlights that ultrasound alone is ultimately limited in reaching a definitive diagnosis. The roles of other investigations such as ultrasound-guided biopsy and cross-sectional imaging are discussed. 相似文献
98.
99.
Human ovarian cancers express somatostatin receptors 总被引:8,自引:0,他引:8
Halmos G Sun B Schally AV Hebert F Nagy A 《The Journal of clinical endocrinology and metabolism》2000,85(10):3509-3512
Characteristics of receptors for somatostatin (SST) analog RC-160 on 17 surgical specimens of human epithelial ovarian cancer and two human ovarian cancer lines were determined by ligand competition assays. The expression of mRNA for four SST receptor subtypes (sst1, sst2A, sst3 and sst5) was investigated by RT-PCR. Thirteen of 17 specimens (76%) exhibited high affinity binding sites for RC-160 with Kd = 6.55 nmol/L and a Bmax = 575.4 fmol/mg membrane protein. Specific receptors for RC-160 were also found in xenografts of OV-1063 and UCI-107 human ovarian cancer lines. The mRNA for sst1 was detected in 65% of the ovarian cancer specimens, while the incidence of sst2A, sst3 and sst5 was 65%, 41% and 24%, respectively. Both ovarian cancer cell lines also expressed mRNA for these four subtypes. The presence of these SST receptor subtypes in human ovarian cancers allows the use of SST analogs and their radionuclide and cytotoxic derivatives for the diagnosis and treatment of this malignancy. 相似文献
100.
Porcine thyrotropin releasing hormone is (pyro)glu-his-pro(NH2) 总被引:2,自引:0,他引:2