低剂量粒—巨噬细胞集落刺激因子在肺癌化疗中的应用

３１例肺癌患者大剂量化疗４０例次，采用配对法分成加用低剂量粒－巨噬细胞集落刺激因子（ＧＭ－ＣＳＦ）的治疗组及不加用的对照组（二组均为２０例次）。结果表明，低剂量ＧＭ－ＣＳＦ明显缩短化疗所致白细胞低下的时间：治疗组为１４．５±９．４９天，对照组为１９．４±８．８５天（Ｐ＝０．０２），同时提高白细胞下降最低值：治疗组为３．３５×１０９／Ｌ±１．３７×１０９／Ｌ，对照组为２．９×１０９／Ｌ±１．１８×１０９／Ｌ。低剂量ＧＭ－ＣＳＦ的主要不良反应为发热（８０％）及肌痛、骨痛（１０％）。结果提示：低剂量ＧＭ－ＣＳＦ能支持癌症患者的大剂量化疗及连续化疗     

Increased hepatobiliary clearance of unconjugated thyroxine determines DMP 904-induced alterations in thyroid hormone homeostasis in rats.

4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1,5-a]-pyrimidine (DMP 904) is a potent and selective antagonist of corticotropin releasing factor receptor-1 (CRF1 receptor) with an efficacious anxiolytic profile in preclinical animal models. In subchronic toxicity studies in Sprague-Dawley rats, DMP 904 produced thyroid follicular cell hypertrophy and hyperplasia, and a low incidence of follicular cell adenoma. The current investigations were designed to determine the mode of action by which DMP 904 disrupts thyroid homeostasis in male rats. Five-day treatment with DMP 904 (300 mg/kg/day) dramatically lowered serum thyroxine (T4) to levels below detectable limits (< 1 microg/dl) by 72 h, with concurrent decreases in triiodothyronine (T3, about a 70% decrease) and increases in thyroid stimulating hormone (TSH; about a three-fold increase). DMP 904 increased [125I]T4 total body clearance (Cl tb) (38.21 +/- 10.45 ml/h) compared to control (5.61 +/- 0.59 ml/h) and phenobarbital-treated rats (7.92 +/- 1.62 ml/h). This increase in Cl(tb) was associated with a significant increase in biliary clearance (Cl bile) of unconjugated [125I]T4 (nearly 80-times control rates) and increased liver:blood ratios of T4, suggestive of enhanced hepatic uptake of T4. A single dose of DMP 904 (200 mg/kg) increased mRNA levels of hepatic cytochrome P450s (CYP 3A1 and CYP 2B1) and UDP-glucuronosyltransferases (UGT 1A1 and UGT 1A2). DMP 904 also induced mRNAs of the canalicular transporter, multi-drug resistance protein-2 (Mrp2) and sinusoidal transporters, organic anion transporting proteins (Oatp1 and Oatp2) within 24 h. Western blot analysis confirmed DMP 904 related increases in Oatp2 protein expression. Collectively, these data suggest that DMP 904 is an agonist of the constitutive androstane receptor (CAR) and pregnane X receptor (PXR) and that the decreased serum levels of T4 and T3 resulted from increased hepatobiliary clearance. However, DMP 904 is distinguished from other compounds associated with similar effects on thyroid hormone homeostasis because its effects were primarily related to increased biliary excretion of unconjugated T4.     

激素替代治疗子宫内膜异位症根治术后42例疗效观察

目的:探讨应用激素替代治疗改善子宫内膜异位症根治术后围绝经期症状的疗效和安全性。方法:2002年1月~2004年12月因重度子宫内膜异位症行根治术出现围绝经期症状的患者42例,随机分成2组。观察组22例口服倍美力0.3 mg,1次/d,对照组20例口服利维爱1.25 mg,1次/d。治疗前后检测血清FSH(卵泡刺激素)和E2(雌二醇)水平,记录治疗期间盆腔痛、性交痛等子宫内膜异位症相关症状,Kupperm an(K评分)1次/月。结果:两组治疗后围绝经期症状均明显改善,血清E2水平上升,治疗前后比较差异有显著性意义(P<0.01),无内膜异位症复发表现。治疗后的E2水平观察组高于对照组,两组比较差异有显著性意义(P<0.01),但均在安全范围内。结论:小剂量倍美力和利维爱用于重度子宫内膜异位症根治术后患者,能有效地控制围绝经期症状,安全,无复发。     

大鼠多囊卵巢动物模型卵泡及子宫内膜bcl-2蛋白的表达

目的：探讨bcl-2凋亡调控蛋白在多囊卵巢综合症（PCOS）大鼠卵泡和子宫内膜中的表达及生物学意义。方法：采用免疫组织化学方法及灰度值测定，定量分析bcl—2在PCOS组和对照组的各级卵泡及子宫内膜中表达。结果：bcl-2在两组中的各级卵泡及子宫内膜中均有表达，PCOS组直径在60-120μm的卵泡中bel-2表达显著高于对照组（P＜0.05）。PCOS纽子宫内膜上皮bcl-2表达显著高于对照组（P＜0．05）。姑论：bcl-2在PCOS组印对照组的各级卵泡中均有表达，随着卵泡的增大，bcl-2表达增加，当卵泡直经＞120μm时，细胞凋亡减弱，卵泡的增长加速。PCOS组子宫内膜上皮表达增强，从而抑制PCOS组子宫内膜凋亡，对其子宫内膜的异常增生改变起一事实上作用。     

GM-CSF基因重组腺病毒载体的构建及鉴定

目的：构建人粒细胞-巨噬细胞集落刺激因子（GM-CSF）基因的重组腺病毒载体，为进一步研究GM-CSF基因在肿瘤基因治疗中的应用提供实验基础。方法：采用PCR方法，从重组质粒pcDNA3．1-GM-CSF扩增出GM-CSF基因片段，通过穿梭质粒pShuttle，将带有CMV启动子的目的片段克隆入Adeno-X腺病毒DNA中，获得重组腺病毒DNA，通过脂质体转染HEK293细胞，经包装扩增后，获得重组腺病毒Adeno-X-GM-CSF，PCR鉴定，ELISA法检测表达产物。结果：含GM-CSF基因的重组腺病毒Adeno-X-GM-CSF构建成功，经PCR鉴定和DNA测序等证实了其正确性，重组腺病毒上清液中GM-CSF表达量达26ng／mL。结论：含GM-CSF基因的重组腺病毒构建成功。     

Gastric adenosquamous carcinoma producing granulocyte-colony stimulating factor

We report a case of adenosquamous carcinoma of the stomach that produced granulocyte-colony stimulating factor (G-CSF). The patient, who had an admission diagnosis of advanced gastric cancer, had marked leukocytosis without evidence of infection. After leukemia and metastatic leukemoid reaction were excluded by bone marrow examination, a G-CSF-producing cancer was suspected as the cause of the abnormally elevated serum G-CSF level. The resected stomach tumor was histologically diagnosed as adenosquamous carcinoma; positive expression of G-CSF by tumor cells was shown with immunohistochemical detection, which confirmed the preoperative diagnosis. Recurrent disease in the liver and lymph nodes, accompanied by leukocytosis and re-elevation of serum G-CSF, developed just 3 months after the curative gastrectomy and adjuvant chemotherapy. All of the recurrent disease was resected, restoring normal levels of serum G-CSF. The patient survived for almost 2 years after the initial surgery with extensive chemotherapy, including weekly treatment with paclitaxel, before finally succumbing to liver failure secondary to extensive liver metastasis.     

国产重组人粒细胞集落刺激因子在妇科恶性肿瘤化疗中的应用

目的:探讨不同剂量国产重组人粒细胞集落刺激因子(rhG-CSF)在妇科恶性肿瘤化疗中的疗效,并与进口rhG-CSF比较。方法:98例卵巢癌、宫体癌和宫颈癌患者随机分成3组,分别按75μg·d-1和150μg·d-1剂量皮下注射国产rhG-CSF和进口75μg·d-1 rhG-CSF,直到白细胞或中性粒细胞绝对数升至正常水平以上。结果:不同剂量国产或进口rhG-CSF均能使3组患者血WBC和ANC水平在用药d 4后升至正常水平以上;在初次化疗时,用不同剂量(75μg和150μ)国产和进口(75μg)rhG-CSF升WBC至正常水平的天数无显著差异(P>0.05),但重复化疗期间150μg国产,rhG-CSF升白细胞的疗效显著优于75μg国产或进口rhG-CSF;同等剂量国产rhG-CSF与进口rhG-CSF升WBC效果一致。结论:75μg小剂量国产rhG-CSF在妇科恶性肿瘤初期化疗中升WBC的疗效肯定,重复化疗时较大剂量(150μg)rhG-CSF升WBC的效果优于小剂量rhG-CSF。同等剂量国产rhG-CSF与进口rhG-CSF的疗效无明显差异。     

低氧诱导因子-1α在成纤维细胞中的表达及对毛囊的影响

目的：探讨外源性人低氧诱导因子（HIF）-1α基因在成纤维细胞中的表达及对体外培养人毛囊的影响。方法：通过脂质体将含有HIF—1α cDNA的真核表达载体pcDNA3．0瞬时转染成纤维细胞,应用反转录（RT）-PCR、免疫组化等方法检测HIF-1α在成纤维细胞中的表达。同时通过ELISA检测转染细胞上清液中血管内皮生长因子（VEGF）的表达情况。进一步将该上清加至体外培养的人毛囊和细胞中,显微镜下测量毛囊的平均生长长度,并观察毛囊的形态学变化。并通过四甲基偶氮唑蓝（MTT）法检测加入转染上清的细胞活性。结果：成功地将HIF—1α真核表达载体HIF—1α pcDNA3．0瞬时转染了成纤维细胞,用RT-PCR、免疫组化染色可检测出细胞中HIF—1α的表达,MTT检测转染后细胞活性增强,并且该上清液可以检测出VEGF的表达。该上清可以明显促进体外培养的人毛囊生长．延缓其进入退行期。结论：应用脂质体能够成功地将外源性人HIF—1α基因转染成纤维细胞,并进行有效表达,其表达的HIF—1α可增强细胞活性,且可诱导转染细胞上清液中VEGF的表达,在体外具有促进人毛囊生长的生物学活性。     

PGC-1α与卵巢功能及相关研究进展

过氧化物酶体增殖物激活受体γ共激活因子1α(peroxisome proliferator-activated receptor gamma coactivator 1 alpha,PGC-1α)属于人体内一种重要的核转录辅助激活因子,是线粒体生成的关键调节因子,通过与核受体及转录因子的相互作用参与线粒体的生物合成、适...     

人窦前小卵泡异种移植后卵泡生长及再血管化的评估

目的 评价人卵巢组织经酶消化后分离的窦前小卵泡异种移植到SCID小鼠后的卵泡生长和再血管化情况.方法 采用0.04mg/mlLiberase酶消化卵巢组织,将卵泡吸出,尽可能将全部间质去除,异种移植到卵巢囊,通过病理组织学检查移植物切片中的卵泡分级和形态,用CD34双重免疫组化染色了解移植物中再血管化的情况.结果 移植...