低剂量辐射诱导小鼠脾脏细胞凋亡的适应性反应(英文)

Objective:The aim of the study was to investigate the adaptive response of low-dose radiation-induced apoptosis in mouse spleen cells and its related proteins control mechanism. Methods: Kunming male mice were randomly divided into sham-irradiation group, attacking dose irradiation group (D2) and low-dose radiation + attacking dose irradiation group (D1+D2). After a week the D1+D2 group was given low-dose radiation (doses were 25,50,75 and 100 mGy, dose rate of 12.5 mGy/min), after 6 hours the D2 group and ...     

卡介苗提取物对小鼠脾细胞免疫调节作用的体外实验研究

目的:分离活卡介苗(bacille calmette guérin,BCG)的有效组分,分析其组分的免疫调节活性。方法:采用酶裂解法和超声波破碎法对活BCG进行裂解,通过Sephadex G100凝胶层析对其有效组分进行分离及相对分子质量的测定,用SDS-PAGE凝胶电泳进行鉴定纯度;采用四氮唑蓝(MTT)方法检测小鼠脾细胞的增殖反应,用ELISA方法检测细胞培养上清液中细胞因子的产生。结果:BCG提取液经Sephadex G100层析和SDS-PAGE凝胶电泳分离后得到3个组分BCGE1、BCGE2和BCGE3,相对分子质量分别为42.5×103、36.3×103和28.6×103;BCGE2和BCGE3均能诱导小鼠脾细胞的增殖反应和IL-12、TNF-α等细胞因子的产生,P值分别为0.0001、0.0001和0.0027,并且有剂量效应关系;但BCGE1对小鼠脾细胞的增殖反应无促进作用,P=0.497;BCGE1、BCGE2和BCGE3对小鼠脾细胞产生IL-4无诱导作用,P值分别为0.988、0.889和0.841。结论:BCGE2和BCGE3可能是BCG免疫调节作用的有效组分,对该成分的进一步分离纯化和机制研究,可为BCG的免疫治疗奠定基础。     

Pathologic rupture of the spleen during induction with ATRA in a patient with acute promyelocytic leukemia

Pathological rupture of the spleen is a rare but well recognized complication in hematological malignancies. Early clinical recognition of this life-threatening complication is necessary for rapid intervention. Here, we report on the case of a 26-year-old woman with acute promyelocytic leukemia who presented rupture of the spleen on day +2 of treatment with ATRA plus idarrubicin. In patients with acute leukemia, the presence of a painful abdomen and a sudden drop in hemoglobin levels, should alert of a possible splenic rupture, even without additional symptoms. This would facilitate an early treatment intervention with no modification to the chemotherapy schedule.     

脾脏原发性血管肉瘤临床病理观察

目的:探讨脾脏原发性血管肉瘤（primary angiosarcoma in the spleen,PAS）的临床病理学特征、免疫表型、诊断及鉴别诊断、治疗与预后,以提高对该肿瘤的认识。方法:对1例发生于脾脏的原发性血管肉瘤进行临床与病理学分析并复习相关文献,观察其组织学、免疫组化特征,探讨其临床病理学及预后。结果:患者女性,40岁。以“腹胀、腹痛、乏力1月余”入院。CT显示脾脏多发结节性占位。大体上脾脏正常结构完全消失,呈灰黄多结节状。镜下,肿瘤细胞形态多种多样。肿瘤大部分区域排列呈血窦样或裂隙样;部分区域血管腔相互吻合成复杂的海绵状、蜂窝状;部分区域可见不规则血管样结构沿血窦分布、突向血窦腔内,形成乳头簇结构突入管腔;另外可见分化较差的区域呈实性、梭形细胞结构。细胞异型性在不同区域表现不一致,大部分区域细胞异型性不明显,少部分区域衬覆细胞异型性明显,核分裂象多见（约9个/10 HPF）。肿瘤组织出血明显。免疫组化:肿瘤细胞弥漫表达ERG、CD31、CD34、Vimentin、FLI-1,不表达FⅧ、CD68、SMA、desmin,Ki-67增殖指数约30%。结论:脾脏原发性血管肉瘤非常罕见,但具有特异的组织学特征和免疫表型,需要与脾脏血管瘤、脾窦岸细胞血管瘤、脾窦岸细胞血管肉瘤等脾脏血管源性肿瘤相鉴别。该肿瘤易发生远处脏器转移,预后差,手术后需密切随诊。     

Expression of basic fibroblast growth factor is associated with poor outcome in non-Hodgkin's lymphoma

It is now clear that angiogenesis and angiogenesis factors are important in the pathogenesis of haematological malignancies. High pretreatment levels of serum basic fibroblast growth factor have been shown to be associated with poor prognosis in patients with non-Hodgkin's lymphoma. The aim of this study was to evaluate whether non-Hodgkin's lymphoma cells express basic fibroblast growth factor and/or its receptor (fibroblast growth factor receptor-1) and whether basic fibroblast growth factor expression correlates with basic fibroblast growth factor serum levels, intratumoral microvessel density, and patient outcome. We measured basic fibroblast growth factor by enzyme-linked immunosorbent assay in sera taken from 58 patients with non-Hodgkin's lymphoma before treatment and in 19 of them also after treatment. Pathological specimens at diagnosis were evaluated by immunohistochemistry staining using polyoclonal antibody against factor-VIII-related antigen, basic fibroblast growth factor and fibroblast growth factor receptor-1 to determine the expression of the microvessel count and basic fibroblast growth factor and fibroblast growth factor receptor-1. The lymphoma specimens demonstrated positive staining for basic fibroblast growth factor (in 23%) and fibroblast growth factor receptor-1 (in 58.5%). The patients who expressed basic fibroblast growth factor had a significantly worse progression-free and overall survival than those who did not (P=0.003 and P=0.03 respectively), while patients expressing fibroblast growth factor receptor-1 were less likely to achieve complete remission than those lacking the receptor (33% vs 65%, P=0.047). There was no correlation of basic fibroblast growth factor staining with either serum basic fibroblast growth factor levels or microvessel count. Basic fibroblast growth factor serum levels did not change significantly after treatment These results suggest that non-Hodgkin's lymphoma specimens express basic fibroblast growth factor and its receptor (fibroblast growth factor receptor-1) and this expression is associated with poor patient outcome.     

碱性成纤维细胞生长因子治疗白血病化疗后口腔溃疡

目的　探讨碱性成纤维细胞生长因子在白血病化疗后口腔溃疡治疗中的疗效和安全性。方法　 60例病人随机分为两组 ,各 3 0例。治疗组口腔局部应用碱性成纤维细胞生长因子 ,配合常规处理 ;对照组单纯应用常规处理。结果　治疗组总有效率 86.7% ,对照组总有效率 46.7%。两组总有效率比较差异有非常显著意义 (P <0 .0 1) ,无严重不良反应。结论　碱性成纤维细胞生长因子治疗白血病化疗后口腔溃疡疗效好 ,安全可靠。     

三氯乙烯对豚鼠脾和外周血淋巴细胞凋亡基因表达水平的影响

目的：探讨三氯乙烯（trichloroethylene,TCE）对豚鼠脾和外周血淋巴细胞凋亡基因Bcl-2、BAX、BAD mRNA表达的影响。方法：采用豚鼠最大值法（guinea pig maximizationtest,GPMT）将18只豚鼠随机分为TCE实验组、阴性对照组、阳性对照组,共3组,每组6只。实验采用皮内注射的方式致敏,TCE实验组注射5%TCE（TCE∶橄榄油=5∶95）,阳性对照组注射0.125%2,4-二硝基氯苯（2,4-dinitrochlorobenzene,DNCB）和福氏完全佐剂（Freund＇s adjuvant complete,FCA）等量混合物,阴性对照组注射橄榄油。各组于第1天皮内注射受试物致敏,第8天用受试物涂皮诱导,第15天涂皮激发。于第15天激发后24h,抽取豚鼠外周血,并处死豚鼠摘取脾脏。用荧光定量PCR检测脾和外周血淋巴细胞凋亡基因Bcl-2、BAX和BAD的mRNA表达水平。结果：阳性对照组和TCE实验组动物均出现明显皮肤损害,TCE致豚鼠皮肤变态反应动物模型建立成功。TCE实验组和阳性对照组豚鼠脾淋巴细胞Bcl-2、BAX和BAD的mRNA表达水平均较阴性对照组显著升高（P〈0.01）;但TCE实验组和阳性对照组豚鼠外周血淋巴细胞Bcl-2、BAX和BAD的mRNA表达水平与阴性对照组比较差异无统计学意义（P〉0.05）。结论：三氯乙烯可诱导豚鼠产生明显的皮肤变态反应,对豚鼠脾淋巴细胞凋亡基因表达水平有一定影响。     

XELOX方案联合小牛脾注射液治疗老年晚期胃癌的疗效观察

目的 探讨卡培他滨和奥沙利铂(XELOX方案)联合小牛脾注射液治疗老年晚期胃癌的临床效果及对血清甲状腺转录因子-1(TTF-1)和肿瘤特异性生长因子(TSGF)水平的影响.方法 选取2018年12月至2020年12月间郑州市第二人民医院收治的76例老年晚期胃癌患者,采用抛硬币法分为观察组和对照组,每组38例.对照组患者...     

补气健脾清热中药对恶性肿瘤患者NK细胞活性及生活质量的影响

目的:探讨补气健脾清热中药对恶性肿瘤患者NK细胞活性及生活质量的影响。方法:研究对象为2012年3月至2013年5月收治的112例恶性肿瘤患者,根据治疗方法的不同将其分为对照组与观察组,每组患者56例。对照组患者给予常规的治疗方案,观察组患者给予补气健脾清热中药的治疗方案。观察两组患者治疗前以及治疗20d、40d后的生活质量Karnofsky评分、NRS评分、NK细胞活性,两组患者治疗后的生存质量;两组患者治疗后常见并发症的发病率。结果:两组患者治疗前的KPS评分、NRS评分、NK细胞活性进行比较无显著性差异（P>0.05),治疗20d、40d后的KPS评分、NRS评分、NK细胞活性进行比较均有显著性差异（P<0.05);对照组患者生存质量改善有效率为71.4%,观察组为92.9%,两组进行比较有显著性差异（P<0.05);对照组与观察组两组患者常见并发症的发病率分别为17.9%、5.36%,对照组的发病率显著性的高于观察组,两组进行比较有显著性差异（P<0.05）。结论:对恶性肿瘤患者给予补气健脾清热中药可以有效提高患者的生存质量以及杀伤性细胞的活性,降低不良反应发生率。     

脾多肽联合多西他赛及顺铂治疗中老年晚期非小细胞肺癌疗效观察

目的:观察脾多肽对多西他赛联合顺铂治疗中晚期非小细胞肺癌(NSCLC)的疗效和不良反应.方法:将60例NSCLC患者随机分为两组:脾多肽组(30例):脾多肽联合多西他赛+顺铂;对照组(30例):单用多西他赛+顺铂.脾多肽组于开始联合化疗方案时即给予脾多肽6 ml/d,静脉滴注,连续应用2周.分别于化疗前后对患者血常规(包括外周血白细胞,血小板,血红蛋白),肝肾功能,消化道反应,免疫功能,生存评分,疗效进行评价.结果:脾多肽组及对照组的总有效率分别是46.7%和43.3%.治疗后,脾多肽组的白细胞、红细胞、血红蛋白、血小板较治疗前的下降程度均比对照组低;治疗后,脾多肽组免疫指标:NK细胞、T细胞、CD4阳性细胞百分率及CD4/CD8比值均较治疗前和对照组明显增加.结论:脾多肽联合多西他赛+顺铂治疗晚期非小细胞肺癌可以增加疗效,减轻骨髓毒性,提高机体免疫力,提高患者生存质量和化疗耐受性值得临床推广.     

Polymorphisms of fibroblast growth factor receptor 4 have association with the development of prostate cancer and benign prostatic hyperplasia and the progression of prostate cancer in a Japanese population

Fibroblast growth factor receptor 4 (FGFR4) is a member of a family of transmembrane receptors with ligand-induced tyrosine kinase activity. The Glycine (Gly) to Arginine (Arg) polymorphism at codon 388 (Gly388Arg), which encodes an amino acid in the transmembrane part of the FGFR4 gene, was reported to be associated with an increased risk in some carcinomas. We investigated the association between the Gly388Arg polymorphism or the G or A polymorphism at intron 11 (rs2011077) of FGFR4, which was located 1,213 base pairs apart from the Gly388Arg polymorphism, and the risk of prostate cancer or benign prostate hyperplasia (BPH), and the prostate cancer disease status in Japanese men. Genotypes of Gly388Arg and rs2011077 polymorphisms of FGFR4 were determined in 492 patients with prostate cancer, 165 patients with BPH and 179 male controls. Regarding the Gly388Arg polymorphism, individuals with the ArgArg genotype had a 2.207- and 1.958-fold increased risk of prostate cancer and BPH, and a 1.804-fold increased risk of metastatic prostate cancer compared with those with the GlyGly genotype. Regarding the rs2011077 polymorphism, individuals with the GG genotype had a 6.260- and 3.033-fold increased risk of prostate cancer and BPH, and a 5.550-fold increased risk of metastatic prostate cancer compared with those with the AA genotype. Our results indicate that the FGFR4 Arg allele of the Gly388Arg polymorphism and the G allele of the rs2011077 polymorphism have a significant impact on the development of prostate cancer and BPH, and the progression of prostate cancer in a Japanese population.     

CIK细胞对脾虚型人胃癌裸鼠腹膜移植模型抗肿瘤作用及其机制的实验研究

目的 :探讨CIK细胞对脾虚型人胃癌裸鼠腹膜移植模型的抗肿瘤作用及机制。方法 :在成功制备CIK细胞、建立脾虚型人胃癌裸鼠腹膜移植模型的基础上 ,观察CIK细胞对脾虚型人胃癌裸鼠腹膜移植模型的体内抗肿瘤作用。用放射免疫方法 (RIA )、酶联免疫方法(ELISA)检测CIK细胞在体内抗肿瘤过程中血清和腹水中CEA以及血清IL 2、TNF α、IFN γ、GM CSF含量的变化。结果 :NS对照组裸鼠腹水继续生长 ,与其相比 ,CD3AK组体质量、腹围、腹水量均明显减少 ,P <0 0 1。CIK组较CD3AK组上述指标有进一步显著减少 ,腹水均全部消失 ,其腹水抑制率达 10 0 % ,P <0 0 1;NS对照组裸鼠血清、腹水中CEA含量均保持较高水平 ,与其相比 ,CD3AK组明显减少 ,CIK组较CD3AK组血清中CEA含量进一步显著减低 ,P <0 0 1;另外 ,与NS对照组相比 ,CIK组裸鼠血清中IL 2、TNF α、INF γ、GM CSF含量均显著增加 ,P <0 0 1。结论 :CIK细胞对脾虚型人胃癌腹膜移植裸小鼠模型有更强的体内抗肿瘤活性 ;并可显著减少胃癌细胞CEA的分泌 ,继续分泌IL 2、TNF α、INF γ、GM CSF等细胞因子而发挥直接或间接的抗肿瘤作用。     

Anti-stromal therapy with imatinib inhibits growth and metastasis of gastric carcinoma in an orthotopic nude mouse model

Recent studies have revealed that platelet-derived growth factor (PDGF) plays a role in promoting progressive tumor growth in several organs; however, whether PDGF plays such a role in gastric carcinoma is undetermined. We examined whether inhibition of PDGF receptor (PDGF-R) tyrosine kinase signaling by imatinib affects tumor growth and metastasis in an orthotopic nude mouse model of human gastric carcinoma. TMK-1 human gastric carcinoma cells were injected into the gastric wall of nude mice. Groups of mice (n = 10 each) received sterile water (control), low-dose imatinib (50 mg/kg/day), high-dose imatinib (200 mg/kg/day), cancer chemotherapeutic agent irinotecan (5 mg/kg/week), or imatinib (50 mg/kg/day or 200 mg/kg/day) and irinotecan (5 mg/kg/week) in combination for 28 days. Tumor growth and metastasis were assessed. Resected tumors were analyzed immunohistochemically. Carcinoma-associated fibroblasts, pericytes and lymphatic endothelial cells in stroma expressed high levels of PDGF-R; carcinoma cells did not. Treatment with imatinib alone did not inhibit tumor growth and metastasis; however, treatment with irinotecan alone or combined with imatinib significantly inhibited tumor growth. Only treatment with high-dose imatinib and irinotecan in combination inhibited lymph node and peritoneal metastases. Immunohistochemically, only imatinib alone or in combination with irinotecan was shown to significantly decrease the stromal reaction, microvessel area and pericyte coverage of tumor microvessels. These effects were marked with high-dose imatinib. In conclusion, administration of PDGF-R tyrosine kinase inhibitor in combination with irinotecan appears to impair the progressive growth of gastric carcinoma by blockade of PDGF-R signaling pathways in stromal cells.