苯丁酸钠抑制可移植性人脑胶质瘤增殖机制的探讨

目的 探讨苯丁酸钠对可移植性人脑胶质瘤增殖抑制作用机制。方法 通过流式细胞仪、Western blot及测量瘤块体积，观察苯丁酸钠对胶质瘤体积、细胞周期、GFAP、c-myc和MHC－I的影响。结果 苯丁酸钠可显著抑制胶质瘤细胞的生长，使瘤细胞阻滞于G0／G1期，S期瘤细胞百分比下降，同时分化抗原GFAP、免疫相关抗原MHC－I上调，肿瘤抗原c-myc蛋白表达下调。结论 苯丁酸钠显著抑制胶质瘤细胞的体内增殖是通过诱导胶质瘤细胞向良性分化起作用的。     

肿瘤诱导分化治疗的现状

近年来,诱导分化治疗的研究非常活跃,有的已经应用于临床并取得了效果,可以说肿瘤诱导分化治疗为肿瘤的治疗开辟了新的途径,先将发展现状做一介绍.     

具有肿瘤细胞分化诱导作用的抗生素研究进展

20世纪80年代以来,肿瘤细胞促分化研究取得了长足的进展.目前已发现具有促分化作用的化合物在百种以上,其中有相当一部分已进入Ⅰ期、Ⅱ期临床试验,少数药物如维甲酸已作为分化诱导剂用于临床肿瘤治疗,并显示出一定疗效.分化诱导剂的临床应用为肿瘤治疗增添了新的手段.     

丁酸钠和氯高铁血红素诱导K562细胞分化的信号转导机制

目的　探讨丁酸钠和氯高铁血红素 (hemin ,Hm)诱导K5 6 2细胞向红系分化的信号转导机制。方法　采用台盼蓝拒染法观察丁酸钠和Hemin对K5 6 2细胞生长曲线的影响 ;流式细胞仪进行细胞周期分析 ;联苯胺染色检测药物诱导K5 6 2细胞向红系分化作用。结果　丁酸钠和Hemin呈时间和剂量依赖方式诱导K5 6 2细胞向红系分化 ;ERK抑制剂PD980 5 9增加丁酸钠、降低Hemin诱导的联苯胺阳性率JNK抑制剂SP6 0 0 12 5未影响丁酸钠却降低Hemin的诱导分化作用。结论　在K5 6 2细胞向红系分化过程中 ,ERK正性调节Hemin、负性调节丁酸钠的诱导分化作用 ;同时Hemin而不是丁酸钠的诱导分化过程还需要JNK的活性     

丁酸钠诱导人肝癌SMMC-7721细胞分化及其作用机理的初步探讨

研究了丁酸钠对人肝癌 SMMC-772 1细胞的诱导分化作用。透射电镜观察可见丁酸钠能诱导肝癌细胞的形态结构向正常方向转变 ;微粒子酶免疫技术 (MEIA)定量检测显示实验组细胞 AFP的分泌量减少 ,与对照组有显著性差异 ;流式细胞仪分析表明丁酸钠引起细胞发生 G0 /G1期阻滞 ;RT-PCR检测结果显示 p2 1WAF1表达随丁酸钠处理时间延长逐渐升高。以上结果表明丁酸钠能逆转肝癌细胞的恶性性状 ,诱导其发生分化。上调 p2 1WAF1的表达可能是丁酸钠诱导肝癌细胞分化的关键因素之一。     

癌的分化诱导及分化诱导剂的研究进展

癌的发生与正常细胞的分化受阻有关,成熟过程的改变可导致出现具持续增殖能力的不成熟细胞产生.许多体外建系的人和小鼠白血病细胞在生理的或非生理物质作用下,能被诱导分化成正常或近似正常的细胞,并伴有细胞增殖能力的降低.因此,分化诱导方法有可能单独或联合化疗防治或治疗肿瘤.     

鹿茸精对HL_（60）细胞诱导分化作用的初步研究

鹿茸精对ＨＬ_（６０）细胞诱导分化作用的初步研究杨佩潢，敖翔，于丽敏（大连医学院组胚教研室．大连１１６０２３）近年来．很多学者研究用诱导细胞分化的方法抑制肿瘤的生长．取得了瞩目的成就，出现了不少诱导细胞分化的药物．但是临床疗效尚不够理想。为此，我们选?..     

苯丁酸钠抗肿瘤的广谱诱导分化作用

恶性肿瘤的诱导分化治疗是近年来倍受关注的新策略 ,苯丁酸钠是一种高效、低毒、广谱的诱导分化新药 ,实验表明它对胶质瘤、前列腺癌、黑色素瘤、白血病、淋巴瘤以及化学预防方面都有明显作用。由于临床上可以实现其有效浓度 ,本身低毒可以大剂量口服 ,具有独特的优势。苯丁酸钠与其他药物合用可以增强抗癌效果。该药临床上曾用于治疗尿素合成紊乱、地中海贫血和镰刀型贫血症 ,目前美国正在进行对胶质瘤和前列腺癌的临床Ⅱ期实验 ,前景看好。     

苯丁酸钠对人舌鳞癌Tca8113细胞株p21和survivin基因表达的影响

目的研究苯丁酸钠对人舌鳞癌Tca8113细胞株的生长、凋亡及其对p21和survivin分子表达的影响。方法应用MTT法检测苯丁酸钠对人舌鳞癌Tca8113细胞株的抑制作用,采用流式细胞仪研究苯丁酸钠对人舌鳞癌Tca8113细胞株的细胞周期阻滞和诱导凋亡作用,应用Western blot和RT-PCR检测p21和survivin基因的转录和表达。结果实验表明苯丁酸钠对Tca8113细胞株增殖有明显的抑制作用;流式细胞仪检测显示苯丁酸钠诱导Tca8113细胞株G1期阻滞和细胞凋亡;苯丁酸钠能使p21的mRNA及蛋白质表达升高,同时survivin的mRNA及蛋白质表达下降。结论苯丁酸钠通过刺激p21表达增加和抑制survivin的表达,从而抑制Tca8113细胞株增殖,诱导细胞G1期阻滞和细胞凋亡;并且p21mRNA水平的上升和survivin mRNA水平的下降变化呈负相关(rs=-0.548,P<0.01),二者蛋白表达的变化亦如此(rs=-0.514,P<0.01)。     

全反式维甲酸相关多药耐药机制及其逆转的研究进展

全反式维甲酸（All-trans retinoic acid，ATRA）是急性早幼粒细胞白血病（acute promyelocytic leukemia，APL）有效的诱导分化剂，用于APL患者诱导分化治疗，完全缓解（complete recovery，CR）率可达85％-90％，其良好疗效已被国内外学者所公认。ATRA现已列为APL诱导缓解治疗的首选药物，且广泛用于其它恶性肿瘤的诱导分化治疗。     

New secondary metabolites of phenylbutyrate in humans and rats.

Phenylbutyrate is used to treat inborn errors of ureagenesis, malignancies, cystic fibrosis, and thalassemia. High-dose phenylbutyrate therapy results in toxicity, the mechanism of which is unexplained. The known metabolites of phenylbutyrate are phenylacetate, phenylacetylglutamine, and phenylbutyrylglutamine. These are excreted in urine, accounting for a variable fraction of the dose. We identified new metabolites of phenylbutyrate in urine of normal humans and in perfused rat livers. These metabolites result from interference between the metabolism of phenylbutyrate and that of carbohydrates and lipids. The new metabolites fall into two categories, glucuronides and phenylbutyrate beta-oxidation side products. Two questions are raised by these data. First, is the nitrogen-excreting potential of phenylbutyrate diminished by ingestion of carbohydrates or lipids? Second, does competition between the metabolism of phenylbutyrate, carbohydrates, and lipids alter the profile of phenylbutyrate metabolites? Finally, we synthesized glycerol esters of phenylbutyrate. These are partially bioavailable in rats and could be used to administer large doses of phenylbutyrate in a sodium-free, noncaustic form.     

苯丁酸钠对人肝癌细胞分化及P~(21WAF1/CIP1)表达的调控

目的:探讨苯丁酸钠诱导人肝癌细胞Bel7402,HepG2生长抑制、分化和细胞周期阻滞,以及对抑癌基因P21WAF1 /CIP1表达的影响。方法:培养Bel7402,HepG2,应用MTT比色法观察苯丁酸钠对Bel7402,HepG2的生长抑制作用,倒置相差显微镜观察细胞形态改变,流式细胞术分析细胞周期,以RTPCR检测Bel 7402,HepG2细胞中P21WAF1 /CIP1基因表达水平,WESTERN印记法检测P21WAF1 /CIP1蛋白的表达。结果:苯丁酸钠 2, 4, 8mmol·L-1处理 72h后Bel 7402, HepG2 的抑制率分别为 28. 43 %,57. 61 %, 71. 32 %和 27. 42 %, 57. 11 %, 70. 31 %处理后的细胞成纤维母细胞样改变,细胞阻滞于G期,P21WAF1 /CIP1基因和蛋白表达水平均增强。结论:苯丁酸钠抑制 2种人肝癌细胞株的生长,诱导部分人肝癌细胞分化,使细胞阻滞于G1期,苯丁酸钠能诱导P21WAF1 /CIP1基因的表达,增加P21WAF1 /CIP1蛋白的表达水平。     

ImmunoPET imaging of hematological malignancies: From preclinical promise to clinical reality

Immuno-positron emission tomography (immunoPET) imaging is a paradigm-shifting imaging technique for whole-body and all-lesion tumor detection, based on the combined specificity of tumor-targeting vectors [e.g., monoclonal antibodies (mAbs), nanobodies, and bispecific antibodies] and the sensitivity of PET imaging. By noninvasively, comprehensively, and serially revealing heterogeneous tumor antigen expression, immunoPET imaging is gradually improving the theranostic prospects for hematological malignancies. In this review, we summarize the available literature regarding immunoPET in imaging hematological malignancies. We also highlight the pros and cons of current conjugation strategies, and modular chemistry that can be leveraged to develop novel immunoPET probes for hematological malignancies. Lastly, we discuss the use of immunoPET imaging in guiding antibody drug development.     

Therapeutic effect of miconazole on fungal infection in patients with hematological malignancies

The effectiveness of miconazole was evaluated in 9 documented fungal infections, 4 of which were candidal sepsis. All patients were receiving therapy for hematological malignancies. Miconazole revealed the excellent effect in 3 patients with candidal esophagitis and 1 patient with candidal sepsis and esophagitis. Twelve patients who received miconazole for presumed or documented fungal infection were evaluated for toxicity. No particular side effects, except for only 1 case of mild hepatic dysfunction, were observed. Miconazole is apparently an effective antifungal agents for treatment of systemic fungal infection in patients with hematological malignancies.     

Leukemia, an effective model for chemical biology and target therapy

The rapid rise of chemical biology aimed at studying signaling networks for basic cellular activities using specific, active small molecules as probes has greatly accelerated research on pathological mechanisms and target therapy of diseases. This research is especially important for malignant tumors such as leukemia, a heterogeneous group of hematopoietic malignancies that occurs worldwide. With the use of a chemical approach combined with genetic manipulation, great progress has been achieved over the past few decades on the biological, molecular and cytogenetic aspects of leukemia, and in its diagnosis and therapy. In particular, discoveries of the clinical effectiveness of all-trans retinoic acid and arsenic trioxide in the treatment of acute promyelocytic leukemia and the kinase inhibitors Imatinib and Dasatinib in the treatment of chronic myelogenous leukemia not only make target therapy of leukemia a reality, but also push mechanisms of leukemogenesis and leukemic cell activities forward. This review will outline advances in chemical biology that help our understanding of the molecular mechanisms of cell differentiation and apoptosis induction and target therapy of leukemia.     

The potential of peroxisome proliferator-activated receptor gamma (PPARgamma) ligands in the treatment of hematological malignancies

PPARgamma has emerged as a key regulator of cell growth and survival, whose activity is modulated by a number of synthetic and natural ligands. Here we shall review the activities of PPARgamma ligands in the control of immune cell proliferation, differentiation and apoptosis and their potential therapeutic applications to hematological malignancies.     

中西医结合治疗难治性溃疡性结肠炎55例临床观察

目的 探索中西医结合方法治疗难治性溃疡性结肠炎的方法、疗效及优势.方法 对55例难治性溃疡性结肠炎进行中医辨证论治配合中药灌肠.结果 中药灌肠结合中药内服的疗效显著优于单独服用西药口服的治疗方法.结论 中药灌肠结合中医辨证论治在溃疡性结肠炎的治疗中具有较高的应用价值.     

Clinical studies on cefoperazone and polymyxin B for the treatment of infections in patients with hematological malignancies

Cefoperazone (CPZ) was used for the treatment of 20 febrile episodes in 18 patients with hematological malignancies and polymyxin B (PL) was applied to the antimicrobial decontamination of the digestive tract in 9 patients with acute leukemia during remission induction therapy. The clinical evaluation of effectiveness was as follows: Excellent in 9 patients (45%), good in 6 patients (30%) and poor in 5 patients (25%). In neutropenic patients the overall efficacy rate was 70%. Side effects were recognized in 3 patients. Allergic reactions such as eruption and eosinophilia were seen and transient liver dysfunction was recognized. This study indicates that CPZ is effective for the treatment of infections in patients with hematological malignancies.     

Vascular endothelial growth factor and its receptor as drug targets in hematological malignancies

Angiogenesis is defined as formation of new blood vessels from the preexisting vasculature, a process which is essential for malignant tumor growth. While this has been accepted for solid forms of cancer there is now emerging evidence that progression of hematological malignancies also requires the induction of new blood vessels. Vascular endothelial growth factor (VEGF) is known to be an essential regulator of physiological and pathological angiogenesis. Numerous preclinical and clinical studies have validated VEGF as target for antiangiogenesis and anticancer therapy. With regard to hematological malignancies a stimulating effect of VEGF for proliferation, survival and migration of leukemia cells could be demonstrated. Bone marrow of leukemia patients shows an increased microvessel density as well as VEGF expression. Complete remissions in acute myeloid leukemia (AML) have been reported by targeting the receptor tyrosine kinase system of VEGF. While the pathophysiology behind the contribution of VEGF to leukemia progression is not yet completely understood, VEGF and its receptors may provide promising targets not only in solid tumors but also hematological malignancies such as AML.     

Clinical evaluation of a combination treatment with cefmenoxime and cefsulodin of severe infections in leukemia and related disorders

A combination of cefmenoxime (CMX) and cefsulodin (CFS) which has a broad spectrum on various bacteria including Pseudomonas aeruginosa was evaluated for severe infections associated with hematological malignancies. Seventy one patients were treated with the combination therapy. Among them, 57 patients were evaluable for the effectiveness. Fourteen patients were not evaluable because 10 patients were subjected to additional therapy such as gamma-globulin, interferon, radiation and pulse therapy of a large dose of methylprednisolone, 3 were prophylactically treated and the remaining one was a patient with disseminated bone marrow metastasis of prostatic cancer and not a patient with a hematologic malignancy. Excellent responses were obtained in 24 (42.1%) patients and good response in 12 (21.1%) patients, with a total rate of effectiveness of 63.2%. Three patients who were treated prophylactically and one patient who suffered from prostatic cancer with metastasis to bone marrow, were included in the final evaluation of side effects. Side effects were observed in only one patient (1/61, 1.6%). Mild neutropenia was identified in a patient of 78 years of age in 4 days after the combined regimen was started. Neutropenia disappeared soon after the cessation of the treatment. These results showed that a combination of CMX and CFS was an effective and safe regimen for the treatment of severe infections in patients with hematological disorders.