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51.
Exemestane experience in breast cancer treatment 总被引:2,自引:0,他引:2
P. E. Lnning R. Paridaens B. Thürlimann G. Piscitelli E. di Salle 《The Journal of steroid biochemistry and molecular biology》1997,61(3-6):151-155
Exemestane is a very potent, orally active, selective and long-lasting steroidal irreversible inhibitor of aromatase. It is 150 times more potent than aminoglutethimide (AG) in inhibiting human placental aromatase (Ki of 4.3 and 671 nM, respectively). The compound is presently under phase III evaluation in Europe and the U.S.A. for the treatment of postmenopausal advanced breast cancer (ABC). Clinical pharmacology studies have been carried out with single doses ranging from 0.5 to 800 mg and repeated doses of up to 600 mg a day, in 132 postmenopausal healthy volunteers and in 185 post-menopausal women with ABC. Results obtained using a very specific and sensitive analytical method (high performance liquid chromatography—radioimmunoassay; HPLC—RIA) indicated that exemestane is extremely effective in inhibiting plasma estrogens levels. Estrogen inhibition is clearly evident at 5 mg a day and maximal suppression for E2, E1 and E1S (>85%, >90% and>90%, respectively) is obtained at 10–25 mg a day. Data from non-controlled phase II studies involving more than 400 patients indicated a clear anti-tumour activity in postmenopausal ABC patients failing multiple hormonal treatments. In 62 patients progressing on AG (≥500 mg a day) exemestane treatment resulted in an objective response rate of approximately 24%; disease stabilization ≥24 weeks was observed in an additional 24% of cases. With regard to safety, although daily doses up to 600 mg were administered, the maximal tolerated dose was not achieved; reported symptoms were mainly related to the pharmacological action of the compound and were usually mild to moderate in severity, resulting in the discontinuation of therapy in less than 3% of cases. In conclusion, the available results suggest that exemestane treatment is associated with minimal toxicity, and may be of significant benefit for ABC women who have exhausted conventional therapy. 相似文献
52.
Inhibition enzyme-linked immunosorbent assay for detection of Pseudomonas fluorescens on meat surfaces. 下载免费PDF全文
An inhibition enzyme-linked immunosorbent assay was developed for Pseudomonas fluorescens enumeration of meat surfaces. The assay detected contamination levels as low as 3 x 10(5) bacteria per ml and could be completed within 4 h. It could be used as a framework for a test system for quantifying P. fluorescens spoilage in meat products. 相似文献
53.
M. P. Francescato T. Talon P. E. di Prampero 《European journal of applied physiology and occupational physiology》1995,71(4):355-361
Energy costs and energy sources in karate (wado style) were studied in eight male practitioners (age 23.8 years, mass. 72.3 kg, maximal oxygen consumption (VO2max) 36.8 ml · min–1 · kg–1) performing six katas (formal, organized movement sequences) of increasing duration (from approximately. 10 s to approximately 80 s). Oxygen consumption (VO2) was determined during pre-exercise rest, the exercise period and the first 270 s of recovery in five consecutive expired gas collections. A blood sample for lactate (la–) analysis was taken 5 min after the end of exercise. The overall amount of O2 consumed during the exercise and in the following recovery increased linearly with the duration of exercise (t) from approximately 1.51 (for t equal to 10.5 s (SD 1.6)) to approximately 5.81, for t equal to 81.5 s (SD 1.0). The energy release from la– production (VO21a
–) calculated assuming that an increase of 1 mmol · l–1 la– corresponded to a VO2 of 3 mlO2 · kg–1 was negligible for t equal to or less than 20 s and increased to 17.3 ml · kg–1 (la– = 5.8 mmol · l–1 above resting values) for t equal approximately to 80 s. The overall energy requirement (VO2eq) as given by the sum of VO2 and VO2la
– was described by VO2eq = 0.87 + 0.071 · t (n = 64; r
2 = 0.91), where VO2eq is in litres and t in seconds. This equation shows that the metabolic power (VO2eq · t
–1) for this karate style is very high: from approximately 9.51 · min–1 for t equal to 10 s to approximately 4.91 · min–1 for t equal to 80 s, i.e. from 3.5 to 1.8 times the subjects' VO2max. The fraction of VO2eq derived from the amount of O2 consumed during the exercise increased from 11% for t equal to 10 s to 41 % for t equal to 80 s whereas VO21a
– was negligible far t equal to or less than 20 s and increased to 13 % o for t equal to 80 s. The remaining fraction (from 90% for t equal to 10 s to 46% for t equal to 80 s), corresponding to the amount of O2 consumed in the recovery after exercise, is derived from anaerobic alactic sources, i.e. from net splitting of high energy phosphates during the exercise. 相似文献
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55.
A total of 51 restriction sites were recognized within the BK virus genome by the combination of 10 different restriction endonucleases. These sites were mapped and oriented relative to one another as well as to the five fragments generated by the digestion of BK virus DNA with HindIII and EcoRI. The result was a comprehensive physical map suitable for in-depth characterization of the functions of BK virus at the molecular level. 相似文献
56.
C Mangoni di S Stefano M Ruggiero M Brunese S Morelli 《Bollettino della Società italiana di biologia sperimentale》1979,55(14):1398-1404
Metabolic rate of obese patients is reported, recorded to cellular active mass. The metabolic rate is higher in obese patients and the value is diucthy related to individual actual weight. The dinamic-specific action of proteins is normal. 相似文献
57.
58.
Imre Mezö János Seprödi Judit Érchegyi István Teplán Magdolna Kovacs Bela Flerkó 《Peptides》1983,4(2):149-151
Inhibitory analogues of luteinizing hormone-releasing hormone (LH-RH) were prepared with formyl-D-Trp1, acetyl-D-Trp1, valeryl-D-Trp1, tartaryl-D-Trp1, diacetyl-tartaryl-D-Trp1, acetyl-Gly1, and acetyl-Sar1 successively replacing the position one in the analogue [D-Trp1, D-p-Cl-Phe2, D-Trp3, D-Phe6, D-Ala10]-LH-RH. The formyl-D-Trp1 and acetyl-D-Trp1 analogues yielded 100% blockade of ovulation at the 10 μg dose; the others were less potent and inhibited ovulation at the 50 μg dose. The inhibitory potency seems to correlate with the polarity of the acyl group. 相似文献
59.
B Vincze I Pályi D Daubner T Kremmer I Számel I Bodrogi J Sugár J Sepr?di I Mez? I Teplán 《The Journal of steroid biochemistry and molecular biology》1991,38(2):119-126
The specific binding of luteinizing hormone-releasing hormone (LH-RH) agonist in estradiol-dependent MCF-7 and estradiol-independent MDA-MB-231 human breast cancer cells has been studied using [3H]Ovurelin [(D-3H-Phe6),des-Gly10-LH-RH- ethylamide]. The results of Scatchard analyses suggest the presence of a single class of receptor sites, both in cell suspensions and membrane fractions. Evaluation of these peptide receptors appears to reflect additional characteristics of biological behaviour of these human breast cancer cells. The synthetic LH-RH agonist Ovurelin [(D-Phe6),des-Gly10-LH-RH-ethylamide] can directly interfere (25-30%) with the proliferation of MDA-MB-231 human breast cancer cells in culture. The inhibitory effect of Ovurelin in vitro was negligible in the MCF-7 cell line. In the in vivo experiments the treated immunosuppressed mice bearing either MCF-7 or MDA-MB-231 xenografts responded to the high-dose LH-RH analogue Zoladex depot and Decapeptyl depot therapy. Since the MDA-MB-231 tumour was found to be ER-negative it seems possible that the regression of this xenograft results from the direct antitumor action of the LH-RH agonist. 相似文献
60.