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101.
102.
目的 分析北京大学肿瘤医院紫杉醇治疗乳腺癌时发生的不良反应,提高对紫杉醇的认识,以便更好地发挥紫杉醇的治疗作用.方法 回顾并分析2014年7月—2016年12月北京大学肿瘤医院上报的81例紫杉醇治疗乳腺癌的不良反应.结果 发生紫杉醇不良反应的乳腺癌患者年龄以50~59岁居多,发生时间基本出现在输注30 min内,不良反应主要症状为胸闷憋气(88.89%)、骨髓抑制(77.78%)、皮肤瘙痒(33.33%)和血压下降(33.33%).51例为首次输注,16例发生不良反应的患者有过敏史.结论 应用紫杉醇化疗的乳腺癌患者先进行预处理方案及试验量输注,可减少不良反应发生.患者输注过程中应密切关注,出现不良反应积极对症处理. 相似文献
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Chemotherapeutics in the taxane and vinca-alkaloid classes sometimes produce a painful peripheral neuropathy for which there is no validated treatment. Experiments with rat models of paclitaxel- and vincristine-evoked pain suggest that these conditions may not respond to all of the analgesics that have efficacy in other models of painful peripheral neuropathy. We tested gabapentin as a potential analgesic for paclitaxel- and vincristine-evoked pain. We used a repeated dosing paradigm because there are precedents showing that repeated drug exposure may be necessary to demonstrate analgesia in neuropathic pain models. Gabapentin is believed to work via binding to voltage-gated calcium channels that contain the alpha-2-delta type-1 (alpha(2)delta-1) subunit, and the expression of this subunit is known to be increased in some painful peripheral neuropathy models. Thus we also examined whether the paclitaxel-evoked pain syndrome was accompanied by an alpha(2)delta-1 increase, and whether gabapentin had any effect on subunit expression. We found that the paclitaxel- and vincristine-evoked mechano-allodynia and mechano-hyperalgesia were significantly reduced by gabapentin, but only with repeated dosing. Paclitaxel-evoked painful peripheral neuropathy was associated with an increased expression of the alpha(2)delta-1 subunit in the spinal dorsal horn, but not in the dorsal root ganglia. The spinal cord increase was normalized by repeated gabapentin injections. Together, these findings suggest that repeated dosing with gabapentin may be beneficial in patients with chemotherapy-evoked painful peripheral neuropathy and that gabapentin's mechanisms of action may include normalization of the nerve injury-evoked increase in calcium channel alpha(2)delta-1 subunit expression. 相似文献
105.
目的分析自身免疫性早发性卵巢功能不全(POI)患者血清免疫指标水平,筛选出较为特异的免疫性指标。 方法选取46例自身免疫性POI患者(POI组)和46例健康女性(正常组),比较两组体液免疫指标、自身免疫指标、抗心磷脂综合征指标、甲状腺功能指标水平。 结果与正常组比较,POI组孕产次、经期及月经周期减少,卵泡刺激素、黄体生成素升高,雌二醇、抗苗勒氏管激素降低;体液免疫指标κ轻链、λ轻链、免疫球蛋白G、免疫球蛋白M、免疫球蛋白E升高,补体4降低;抗心磷脂综合征指标抗心磷脂IgA抗体(ACA-IgA)、ACA-IgG、抗β2糖蛋白1 IgM抗体升高;甲状腺功能指标游离三碘甲状腺原氨酸、游离甲状腺素、促甲状腺素受体抗体、甲状腺过氧化物酶抗体升高(P<0.05),上述指标阳性率两组间比较差异有显著性(P<0.05)。POI组内与自身免疫指标阳性率比较,体液免疫指标阳性率和甲状腺功能指标阳性率差异均有显著性。 结论自身免疫性POI患者血清体液免疫指标和甲状腺功能指标更容易发生异常。 相似文献
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Sara Jane Ward Sean D McAllister Rumi Kawamura Ryuchi Murase Harshini Neelakantan Ellen A Walker 《British journal of pharmacology》2014,171(3):636-645
Background and Purpose
Paclitaxel (PAC) is associated with chemotherapy-induced neuropathic pain (CIPN) that can lead to the cessation of treatment in cancer patients even in the absence of alternate therapies. We previously reported that chronic administration of the non-psychoactive cannabinoid cannabidiol (CBD) prevents PAC-induced mechanical and thermal sensitivity in mice. Hence, we sought to determine receptor mechanisms by which CBD inhibits CIPN and whether CBD negatively effects nervous system function or chemotherapy efficacy.Experimental Approach
The ability of acute CBD pretreatment to prevent PAC-induced mechanical sensitivity was assessed, as was the effect of CBD on place conditioning and on an operant-conditioned learning and memory task. The potential interaction of CBD and PAC on breast cancer cell viability was determined using the MTT assay.Key Results
PAC-induced mechanical sensitivity was prevented by administration of CBD (2.5 – 10 mg·kg−1) in female C57Bl/6 mice. This effect was reversed by co-administration of the 5-HT1A antagonist WAY 100635, but not the CB1 antagonist SR141716 or the CB2 antagonist SR144528. CBD produced no conditioned rewarding effects and did not affect conditioned learning and memory. Also, CBD + PAC combinations produce additive to synergistic inhibition of breast cancer cell viability.Conclusions and Implications
Our data suggest that CBD is protective against PAC-induced neurotoxicity mediated in part by the 5-HT1A receptor system. Furthermore, CBD treatment was devoid of conditioned rewarding effects or cognitive impairment and did not attenuate PAC-induced inhibition of breast cancer cell viability. Hence, adjunct treatment with CBD during PAC chemotherapy may be safe and effective in the prevention or attenuation of CIPN. 相似文献108.
Synthesis and Evaluation of a CBZ‐AAN‐Dox Prodrug and its in vitro Effects on SiHa Cervical Cancer Cells Under Hypoxic Conditions 下载免费PDF全文
Hongyuan Chen Xiao Liu Eric S. Clayman Fangyuan Shao Manshan Xiao Xuyan Tian Wuyu Fu Caiyun Zhang Bibo Ruan Pengjun Zhou Zhong Liu Yifei Wang Wen Rui 《Chemical biology & drug design》2015,86(4):589-598
Although doxorubicin (Dox) is widely used in clinical treatment for solid tumors, it causes many side‐effects such as heart and kidney damage, bone marrow suppression, and drug resistance. Legumain is a lysosomal protease that is elevated and associated with an invasive and metastatic phenotype in a number of solid tumors. In this study, we designed and synthesized a Dox prodrug, N‐benzyloxycarbonyl‐Ala‐Ala‐Asn‐Doxorubicin (CBZ‐AAN‐Dox), with 94% purity. Single substrate kinetic assays demonstrated hLegumain‐specific enzymatic cleavage and activation of the prodrug in vitro, and this enzymatic cleavage of the prodrug substrate was more sensitive in acidic conditions, releasing more than 70% of Dox after 24 h. Treatment of tumor cells with our prodrug demonstrated a much higher IC50 value, significantly enhanced uptake of the prodrug, and considerably less cellular toxicity compared to Dox treatment alone. Our study presents a novel prodrug, CBZ‐AAN‐Dox, to potentially increase both the safety and efficacy of clinical treatment of tumors by exploiting the tumor's innate expression of legumain. 相似文献
109.
Jos M. Cornejo-Bravo Kenia Palomino Giovanni Palomino-Vizcaino Oscar M. Prez-Landeros Mario Curiel-Alvarez Benjamín Valdez-Salas Emilio Bucio Hctor Magaa 《Materials》2021,14(5)
New medical devices with anti-inflammatory properties are critical to prevent inflammatory processes and infections in medical/surgical procedures. In this work, we present a novel functionalization of silicone for medical use with a polymeric prodrug and a thermosensitive polymer, by graft polymerization (gamma rays), for the localized release of salicylic acid, an analgesic, and anti-inflammatory drug. Silicone rubber (SR) films were functionalized in two stages using graft polymerization from ionizing radiation (60Co). The first stage was grafting poly(N-vinylcaprolactam) (PNVCL), a thermo-sensitive polymer, onto SR to obtain SR-g-PNVCL. In the second stage, poly(2-methacryloyloxy-benzoic acid) (P2MBA), a polymeric prodrug, was grafted to obtain (SR-g-PNVCL)-g-P2MBA. The degree of functionalization depended on the concentrations of monomers and the irradiation dose. The films were characterized by attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy/energy-dispersive X-ray spectrometry (SEM–EDX), thermogravimetric analysis (TGA), and contact angle. An upper critical solution temperature (UCST) of the films was demonstrated by the swelling degree as a temperature function. (SR-g-PNVCL)-g-P2MBA films demonstrated hydrolysis-mediated drug release from the polymeric prodrug, pH, and temperature sensitivity. GC–MS confirmed the presence of the drug (salicylic acid), after polymer hydrolysis. The concentration of the drug in the release media was quantified by HPLC. Cytocompatibility and thermo-/pH sensitivity of functionalized medical silicone were demonstrated in cancer and non-cancer cells. 相似文献
110.
Richard N. Fedorak Barbara Haeberlin Lonnie R. Empey Ningren Cui Harold Nolen III Laurence D. Jewell David R. Friend 《Gastroenterology》1995,108(6):1688-1699
Dexamethasone-β-d-glucuronide, a colon-specific prodrug of dexamethasone, may be useful in the treatment of ulcerative colitis and Crohn's colitis. The aim of this study was to evaluate colonic delivery and efficacy of this prodrug in the rat. Distribution of dexamethasone in luminal contents and tissues of the gastrointestinal tract and in plasma was measured after oral administration of dexamethasone-β-d-glucuronide or free dexamethasone. Efficacy of the prodrug and free drug was tested in an acetic acid-induced rat colitis model. Healing of induced colitis was assessed by measuring net intestinal fluid absorption, colonic surface area of ulceration, histology, and myeloperoxidase activity. Glucocorticosteroid toxicity was evaluated with serum corticosterone and plasma adrenocorticotropic hormone levels. The drug delivery index (a measure of relative targeting efficiency) was 6.7 and 8.6 in the cecal and colonic mucosa, respectively. The prodrug was significantly more potent than free drug in improving net colonic fluid absorption while significantly reducing surface area of ulceration and histological grade in colitic rats. Treatment with free dexamethasone significantly reduced serum corticosterone levels to subnormal levels, and treatment with the prodrug maintained serum corticosterone and plasma adrenocorticotropic hormone levels near control levels. The prodrug dexamethasone-β-d-glucuronide delivers efficacious amounts of dexamethasone to the large intestine from lower doses than free dexamethasone. 相似文献