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101.
Nineteen racemic ring A substituted analogues of the antitumor agent 20(S)-camptothecin were prepared by total synthesis and evaluated for in vitro cytotoxic activity against KB cell culture and in vivo antileukemic activity against L1210. These compounds bore a wide variety of substituents at C11 designed to confer upon the ring system a broad range of combinations of electronic, steric, and lipophilic effects. A few C10-substituted derivatives as well as C10,C11-disubstituted analogues prepared as part of a concurrent study have also been included for general comparison. With the notable exception of the cyano derivative, the 11-substituted compounds displayed only modest in vitro and in vivo activities, and there was a remarkable insensitivity toward the nature of the substituent. In contrast, the 9- and 10-substituted compounds exhibited a considerably higher level of dose potency and activity both in vitro and in vivo. 相似文献
102.
G Javid B Khan M M Wani A Shah G M Gulzar B Khan 《Indian journal of gastroenterology》1999,18(1):15-17
BACKGROUND: Although upper gastrointestinal endoscopy is generally a safe procedure, it is known to be associated with arterial oxygen desaturation, resulting in rare serious cardio-pulmonary events. OBJECTIVE: To determine the severity of oxygen desaturation during nonsedated upper gastrointestinal endoscopy and study the effect of various variables on oxygen saturation. METHODS: 126 patients underwent nonsedated upper gastrointestinal endoscopy (82 diagnostic, 44 therapeutic). Arterial oxygen saturation (SaO2) was monitored using a pulse oximeter. RESULTS: Baseline SaO2 was mean (SD) 97.8 (1.8%). It remained > 95% in 60.2% of patients during the procedure, whereas mild oxygen desaturation (SaO2 90%-94%) occurred in 23.7% and severe oxygen desaturation (SaO2 < 90%) occurred in 15.8% of patients. Six patients (4.7%) required supplemental oxygen administration sometime during the procedure. Desaturation occurred in patients undergoing diagnostic and therapeutic procedures but was severe in the latter group (p < 0.002). Patients aged more than 60 years (p < 0.001), hemoglobin < 10 g/dL (p < 0.001), history of smoking (p < 0.001), and underlying chronic obstructive airway disease (p < 0.001) were significantly related to oxygen desaturation. However, on multivariate analysis, no significant correlation was observed with hemoglobin value. CONCLUSION: Therapeutic intervention during nonsedated upper gastrointestinal endoscopy, old age, smokers and chronic obstructive airways disease are independent risk factors for oxygen desaturation. We recommend continuous monitoring of SaO2 in these high-risk patients undergoing upper gastrointestinal endoscopy. 相似文献
103.
Plant antitumor agents. 23. Synthesis and antileukemic activity of camptothecin analogues 总被引:8,自引:0,他引:8
Eight optically active and nine racemic ring A modified analogues of 20(S)-camptothecin were prepared and evaluated for antitumor activity in the L-1210 leukemia system. The ring A mono- and disubstituted analogues displayed a wide variance in activity and potency. It was found that monosubstitution by NH2 or OH at positions 9, 10, or 11 yielded compounds with activity much higher than the parent compound, camptothecin, whereas substitution at position 12 greatly reduced activity. In general, disubstitution in ring A greatly reduced antileukemic activity. Replacement of ring A by heterocyclic rings (thiophene or pyridine) leads to analogues with only moderate activity. 相似文献
104.
淋巴靶向制剂——吸附抗癌药毫微粒活性炭的研究进展 总被引:12,自引:0,他引:12
目的介绍新型淋巴靶向制剂———吸附抗癌药毫微粒活性炭的研究进展。方法依据近年来的文献 ,对活性炭的制备工艺及体内外性质等方面进行了综述。结果活性炭具有很强的吸附功能 ,普通市售活性炭仅用作脱色、吸附热原与除味等。以微粒球磨机为粉碎器械 ,可加工制备粒径达1 0 0nm左右的纳米炭微粒 ,具有优越的淋巴趋向性。结论吸附抗癌药毫微粒活性炭在临床治疗癌症方面具有良好的运用前景 相似文献
105.
Gamcsik MP Kasibhatla MS Adams DJ Flowers JL Colvin OM Manikumar G Wani M Wall ME Kohlhagen G Pommier Y 《Molecular cancer therapeutics》2001,1(1):11-20
Depletion of glutathione (GSH) in MCF-7 and MDA-MB-231 cell lines by pretreatment with the GSH synthesis inhibitor buthionine sulfoximine potentiated the activity of 10,11-methylenedioxy-20(S)-camptothecin, SN-38 [7-ethyl-10-hydroxy-20(S)-camptothecin], topotecan, and 7-chloromethyl-10,11-methylenedioxy-20(S)-camptothecin (CMMDC). The greatest potentiation was observed with the alkylating camptothecin CMMDC. Buthionine sulfoximine pretreatment also increased the number of camptothecin-induced DNA-protein crosslinks, indicating that GSH affects the mechanism of action of camptothecin. We also report that GSH interacts with CMMDC to form a stable conjugate, 7-(glutathionylmethyl)-10,11-methylenedioxy-20(S)-camptothecin (GSMMDC), which is formed spontaneously in buffered solutions and in MCF-7 cells treated with CMMDC. GSMMDC was synthesized and found to be nearly as active as 10,11-methylenedioxy-20(S)-camptothecin in a topoisomerase (topo) I-mediated DNA nicking assay. The resulting topo I cleavage complexes were remarkably stable. In cell culture, GSMMDC displayed potent growth-inhibitory activity against U937 and P388 leukemia cell lines. GSMMDC was not active against a topo I-deficient P388 cell line, indicating that topo I is its cellular target. Peptide-truncated analogues of GSMMDC were prepared and evaluated. All three derivatives [7-(gamma-glutamylcysteinylmethyl)-10,11-methylenedioxy-20(S)-camptothecin, 7-(cysteinylglycylmethyl)-10,11-methylenedioxy-20(S)-camptothecin, and 7-(cysteinylmethyl)-10,11-methylenedioxy-20(S)-camptothecin] displayed topo I and cell growth-inhibitory activity. These results suggest that 7-peptidyl derivatives represent a new class of camptothecin analogues. 相似文献
106.
TA Fredriksen MM Wysocka-Bakowska A Bogucki F Antonaci 《Cephalalgia : an international journal of headache》1988,8(2):93-103
Eleven female patients with cervicogenic headache (mean age, 43 years; range, 25-59 years) have been examined with the pupillometer. The pupillary diameter was examined in the basal state (that is, the status before pharmacologic stimulation) and after topically administered tyramine (2%), phenylephrine (1%), and hydroxyamphetamine (1%). A total of 51 tests were performed, 35 in the asymptomatic period and 16 during pain attacks. In a control group consisting of 26 age-matched women a total of 39 tests were carried out. Before pharmacologic stimulation (that is, in the "basal state") the pupils were smaller in the asymptomatic (pain-free) period than during pain attacks in the patients and also as compared with that of control individuals. The anisocoria (the difference in pupillary size in the same individual) observed was not significantly different between the patient group and control individuals either in the basal state (before pharmacologic stimulation) or after pharmacologic stimulation. The mydriasis resulting from the instillation of the three sympathicomimetic drugs was symmetrical in both controls and patients both during and between the pain attacks. This finding is in clear contrast to what is found in cluster headache, in which there is a "Horner-like" syndrome on the symptomatic side. These two headaches thus seem to differ essentially with regard to this variable. 相似文献
107.
108.
109.
The Viral Activation Transfusion Study (VATS): rationale, objectives, and design overview 总被引:1,自引:0,他引:1
110.
Granulocyte (PMN) concentrates collected for transfusion to septic, neutropenic patients are stored in the blood bank for various periods of time before they are given. Current methods of blood bank storage of PMN concentrates are associated with impaired in vitro PMN chemotaxis (CTX) and in vivo recovery and circulation kinetics after 24 hours of storage. This suggested the possibility that PMN may become hyperadherent during storage. To test this hypothesis, PMN concentrates were harvested and stored at both 22 and 6 degrees C and their adherence properties to relevant biologic surfaces, endothelial cell (EC) monolayers, and extracellular matrix (ECM) derived from endothelium were measured. Adherence was measured within 4 hours of collection and after 24 and 48 hours of storage. The aggregation properties of fresh and stored PMN were also studied. The adherence of fresh, unstimulated PMN to EC and ECM (31 +/- 5% and 34 +/- 4%, respectively) increased significantly after storage for 24 hours (EC = 41 +/- 8%; ECM = 43 +/- 4%) at 22 degrees C. F-Met-Leu-Phe (FMLP) stimulated the adherence of fresh PMN (EC = 37 +/- 4%; ECM = 42 +/- 4%; p less than 0.05). The adherence of PMN stored at 22 degrees C was further stimulated by FMLP (EC = 46 +/- 6%; ECM = 50 +/- 4%). PMN stored at 6 degrees C had significantly higher adherence than PMN stored at 22 degrees C, and the percentage of increase in adherence induced by FMLP was attenuated in PMN stored at 6 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献