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131.
目的:研究和改进甲磺酸达比加群酯的合成工艺。方法:以4-甲氨基-3-硝基苯甲酸(2)和3-(吡啶-2-基氨基)丙酸乙酯(3)为原料,经酰氯化、酰胺化、中和成盐和还原制得重要中间体3-[[3-氨基-4-(甲氨基)苯甲酰基](吡啶-2-基)氨基]丙酸乙酯(5)。5再与N-(4-氰基苯基)甘氨酸经酰胺化、闭环、中和成盐、成脒、酰化,进而与甲磺酸成盐制得甲磺酸达比加群酯。结果:中间体及目标化合物经质谱、核磁共振谱、红外光谱等确证,整个工艺的总收率为33.9%。结论:本路线操作简便、成本较低、条件温和、步骤少,适合工业化生产。 相似文献
132.
慢性期慢性髓性白血病患者接受伊马替尼一线治疗后,虽然大部分患者可显著获益,但仍有相当比例的患者不能获得满意疗效。如果患者未获得满意疗效,则依然存在疾病进展风险。因此,对于伊马替尼治疗失败或疗效欠佳的患者,需要考虑转换其他替代治疗,以得到最大获益。研究显示伊马替尼治疗失败的患者换用第2代TKI——尼洛替尼治疗获益显著。本文综述了伊马替尼治疗失败的患者换用尼洛替尼后的疗效并对换用时机进行探讨。 相似文献
133.
134.
BackgroundThe aim of the study was to determine the type of interaction between pregabalin (a 3rd-generation antiepileptic drug) and WIN 55,212-2 mesylate (WIN – a highly potent non-selective cannabinoid CB1 and CB2 receptor agonist) administered in combination at a fixed ratio of 1:1, in the acute thermal pain model (hot-plate test) in mice.MethodsLinear regression analysis was used to evaluate the dose-response relationships between logarithms of drug doses and their resultant maximum possible antinociceptive effects in the mouse hot-plate test. From linear equations, doses were calculated that increased the antinociceptive effect by 30% (ED30 values) for pregabalin, WIN, and their combination. The type of interaction between pregabalin and WIN was assessed using the isobolographic analysis.ResultsResults indicated that both compounds produced a definite antinociceptive effect, and the experimentally-derived ED30 values for pregabalin and WIN, when applied alone, were 29.4 mg/kg and 10.5 mg/kg, respectively. With isobolography, the experimentally derived ED30 mix value for the fixed ratio combination of 1:1 was 5.7 mg/kg, and differed significantly from the theoretically calculated ED30 add value of 19.95 mg/kg (p < 0.01), indicating synergistic interaction between pregabalin and WIN in the hot-plate test in mice.ConclusionsIsobolographic analysis demonstrated that the combination of WIN with pregabalin at a fixed ratio of 1:1 exerted synergistic interaction in the mouse model of acute thermal pain. If the results from this study could be adapted to clinical settings, the combination of WIN with pregabalin might be beneficial for pain relief in humans. 相似文献
135.
目的:探讨伊马替尼与干扰素联合化疗治疗慢性粒细胞白血病(CM L)的疗效。方法:2004年6月—2009年7月新诊断的58例Ph染色体阳性CM L慢性期患者,随机分为伊马替尼组和干扰素联合化疗组,比较两组临床疗效。结果:两组总有效率差异无统计学意义(P>0.05);伊马替尼组完全血液学缓解率,完全细胞遗传学缓解率、完全分子学效应率、5年总生存率均明显高于干扰素联合化疗组(P<0.05)。结论:伊马替尼和干扰素联合化疗都可作为CM L慢性期的有效治疗方法,应依据不同情况实施个体化治疗。 相似文献
136.
137.
Aim The aim of this study was to explore the effects and mechanism of berbamine on imatinib-resistant BCR-ABL-positive human leukemia K562 (K562-r) cells in vitro and in vivo. Methods:Cell viability was measured by MTT assay, and apoptotic morphology changes were detected by fluorescence microscopy. The apoptosis rate was measured by flow cytometric assay, mdr-1 mRNA levels were determined by RT-PCR. Bcl-2 family proteins, cytochrome c( cyt C) , poly (ADP-ribose) polymerase (PARP), and P-glycoprotein were detected by Western blot. BALB/c nu/nu mice were injected with K562-r cells subcutaneously. Tumor-bearing mice were treated intravenously with berbamine.
Results: MTT tests revealed that berbamine significantly inhibited K562-r cell proliferation and increased the chemosensitivity of K562-r cells to imatinib. The apoptosis rate was significantly increased following treatment with 21.2μmol/L berbamine; formation of typical apoptotic blebs was apparent, as observed by fluorescence microscopy. Expression levels of mdr-I mRNA and P-gp protein were high in untreated K562-r cells and significantly down-regulated by berbamine treatment. Berbamine-treated K562-r cells also exhibited down-regulated expression of the anti-apoptotic proteins Bcl-2 and Bcl-XL up-regulated expression of the apoptotic proteins Bax and cytoplasmic cyt C, and stimulated proteolytic cleavage of PARP. In addition, berbamine also suppressed the growth of K562-r xenotransplanted tumors in vivo.
Conclusion Berbamine inhibited proliferation of K562-r ceils both in vitro and in vivo. Berbamine-induced apoptosis in K562-r cells appeared to occur through a mechanism involving Bcl-2 family proteins, as well as mdr-1 mRNA and P-gp pro- tein. Berbamine in combination with imatinib restored the chemo-sensitivity of K562-r cells to imatinib. Our findings suggest that berbamine may be useful in treating imafinib-resistant CML patients. 相似文献
Results: MTT tests revealed that berbamine significantly inhibited K562-r cell proliferation and increased the chemosensitivity of K562-r cells to imatinib. The apoptosis rate was significantly increased following treatment with 21.2μmol/L berbamine; formation of typical apoptotic blebs was apparent, as observed by fluorescence microscopy. Expression levels of mdr-I mRNA and P-gp protein were high in untreated K562-r cells and significantly down-regulated by berbamine treatment. Berbamine-treated K562-r cells also exhibited down-regulated expression of the anti-apoptotic proteins Bcl-2 and Bcl-XL up-regulated expression of the apoptotic proteins Bax and cytoplasmic cyt C, and stimulated proteolytic cleavage of PARP. In addition, berbamine also suppressed the growth of K562-r xenotransplanted tumors in vivo.
Conclusion Berbamine inhibited proliferation of K562-r ceils both in vitro and in vivo. Berbamine-induced apoptosis in K562-r cells appeared to occur through a mechanism involving Bcl-2 family proteins, as well as mdr-1 mRNA and P-gp pro- tein. Berbamine in combination with imatinib restored the chemo-sensitivity of K562-r cells to imatinib. Our findings suggest that berbamine may be useful in treating imafinib-resistant CML patients. 相似文献
138.
Wcislo G Szarlej-Wcislo K Szczylik C 《Journal of cancer research and clinical oncology》2007,133(8):533-538
Objective There has been only one report available that focuses on the treatment with imatinib mesylate of two individual persons with
aggressive fibromatosis. The authors concluded that after long-term treatment, for 9 and 11 months, with imatinib mesylate,
both patients demonstrated radiographic and clinical responses. The novel therapy should be considered as salvage in patients
with aggressive fibromatosis expressed platelet-derived growth factor receptor—alfa, beta (PDGFR-alfa, PDGFR-beta), and/or
c-kit, whose tumors are uncontrollable by the standard management. On the other hand, the number of kinases blocked by imatinib
mesylate is notching up, for instance the tyrosine kinase, which is associated with macrophage-colony stimulating factor receptor
(M-CSFR).
Methods The patient was suffering from aggressive fibromatosis after prior therapy including surgery (R2), radiotherapy, and systemic
treatment with combination of tamoxifen and sulindac. The tumor specimen was immunostained for PDGFR-beta and c-kit (CD117),
and PDGFR-alfa and cytokines platelet-derived growth factor-alfa and beta were not assessed. The tests for both assessed molecules
revealed negative results. In spite of this, the patient underwent a unique treatment with imatinib mesylate at the dose of
400 mg orally once daily for 3 years and 2 months.
Results After three months of the therapy, radiographic (met criteria of SD but small decrease of the tumor was noted) and clinical
responses were recorded for the first time. The same was seen after 6 and 13 months of therapy continuation with imatinib
mesylate. Currently, the patient is treated with imatinib mesylate (400 mg orally once daily) without any toxicity effects.
The last MRI revealed readily a smaller tumor (35 × 20 mm) after such a therapy lasted more than 3 years.
Conclusions Treatment with imatinib mesyalte has been a well-accepted therapy for chronic myelagenous leukemia (CML) and gastrointestinal
stromal tumors (GIST). There have been established four kinases (p210bcr/abl, c-kit, PDGFR-alfa, PDGFR-beta) suggested as the target for imatinib mesylate. Other potential targets will be discovered
as it has lately been determined that M-CSFR kinase activity was blocked by imatinib mesylate. The salvage therapy for aggressive
fibromatosis with imatinib mesylate seems to be an attractive opportunity for patients with the advanced disease, whose prior
therapy failed. 相似文献
139.
Imatinib mesylate therapy in CML patients is a generally well tolerated without any significant hematological adverse drug effects. However, complications like anemia and cytopenias have been described in literature. A very few case reports of bone marrow aplasia following imatinib therapy have been reported so far. We here report five patients of CML who developed bone marrow aplasia following imatinib therapy. 相似文献
140.
Ueki T Otani K Kawamoto K Shimizu A Fujimura N Sakaguchi S Matsui T 《Journal of gastroenterology》2007,42(2):161-167
Background It has been reported that the administration of ulinastatin, gabexate mesylate, or somatostatin may be effective in the prevention
of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. However, few randomized trials of ulinastatin
and gabexate mesylate for the prevention of post-ERCP pancreatitis have been reported. The aim of this study was to compare
the efficacy of ulinastatin and gabexate mesylate for the prevention of post-ERCP pancreatitis.
Methods Sixty-eight patients who underwent diagnostic ERCP at our hospital were divided at random by computer-generated randomization
into an ulinastatin group (n = 34) and a gabexate group (n = 34). Each patient received a continuous intravenous infusion of ulinastatin (150 000 units) or gabexate mesylate (600 mg),
beginning 60–90 min before the ERCP and continuing until 22 h after the ERCP. The primary endpoint was the incidence of post-ERCP
pancreatitis, and the secondary endpoints were the incidences of hyperenzymemia and pain.
Results The overall incidence of post-ERCP pancreatitis was 2.9% (two patients), comprising one patient in the ulinastatin group and
one patient in the gabexate group (2.9% vs 2.9%, respectively). Neither of these two patients developed severe pancreatitis.
There were no significant differences in the serum levels of pancreatic enzymes or in the levels of pain between the two groups.
Conclusions There was no clinical difference between the effect of preventive administration of ulinastatin and that of gabexate mesylate
on the incidence of post-ERCP pancreatitis. Ulinastatin may be equivalent in efficacy to gabexate for reducing the incidence
of post-ERCP pancreatitis. 相似文献