老年人血清α_1-酸性糖蛋白(α_1-AGP)的临床意义

α_1-酸性糖蛋白(α_1-AGP)是血清微量蛋白之一,其分子量为40,000,等电点pH2.7,电泳移动时在α_1位置,分子结构为单链,含糖总量为37.9％,属急性相反应物。近年来发现很多肿瘤病人血清α_1-AGP含量增高,被认为可能是一种与肿瘤有关的成份,可视为肿瘤的一种标志物。本文以火箭电泳法测定老年前期和老年期健康人,老年肿瘤(主要是胃肠道肿瘤)患者和冠心、慢支、糖尿病患者的α_1-AGP,探讨其临床意义。     

~(238)Puα粒子辐射体外诱发大鼠肺成纤维细胞(WAL-F_1)恶性转化

本文报告了(233)~ρμα粒子辐射体外诱发成年Wistar大鼠肺成纤维细胞(WAL-F_1)恶性的特性。实验结果表明,在0.01～1.50Gy剂量范围,α粒子照射的WAL-F_1细胞的剂量一存活曲线符合单次击中单靶模型,S=e_0~(-D/D),D_0=0.172Gy,没有肩峰(D_0)。(238)~Puα粒子照射后,WAL-F_1细胞的增殖能     

Estrogen receptor α (ERα) mediates 17β-estradiol (E2)-activated expression of HBO1

Background

HBO1 (histone acetyltransferase binding to ORC1) is a histone acetyltransferase (HAT) which could exert oncogenic function in breast cancer. However, the biological role and underlying mechanism of HBO1 in breast cancer remains largely unknown. In the current study, we aimed to investigate the role of HBO1 in breast cancer and uncover the underlying molecular mechanism.

Methods

Immunohistochemistry was applied to detect HBO1 protein expression in breast cancer specimens (n = 112). The expression of protein level was scored by integral optical density (IOD) for further statistical analyses using SPSS. Real-time PCR was used to simultaneously measure mRNA levels of HBO1. The HBO1 protein expression in breast cancer cells was confirmed by western blot.

Results

HBO1 was highly expressed in breast cancer tissues and significantly correlated with estrogen receptor α (ERα) (p < 0.001) and progestational hormone (PR) (p = 0.002). HBO1 protein level also correlated positively with histology grade in ERα positive tumors (p = 0.016) rather than ERα negative tumors. 17β-estradiol (E2) could upregulate HBO1 gene expression which was significantly inhibited by ICI 182,780 or ERα RNAi. E2-increased HBO1 protein expression was significantly suppressed by treatment with inhibitor of MEK1/2 (U0126) in T47 D and MCF-7 cells.

Conclusions

HBO1 was an important downstream molecule of ERα, and ERK1/2 signaling pathway may involved in the expression of HBO1 increased by E2.     

Hypoxia-Inducible Factor1-Α (HIF1α) and Vascular Endothelial Growth Factor-A (VEGF-A) Expression in De Novo AML Patients

Background: Bone marrow hypoxia can promote leukemia progression in human cases of acute myeloid leukemia(AML). In addition, low oxygen tension is able to regulate the expression of different genes involved in malignancy.In this study, we hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF-A) genes wereassessed as principal regulators of hypoxia in do novo AML patients. Methods: Peripheral blood and bone marrowsamples were collected from 57 AML patients and 17 normal control subjects with informed consent. Expression ofHIF1α and VEGF-A was then evaluated using quantitative real-time PCR (Q-Real time PCR) and data were analyzedwith SPSS 16. Result: HIF1α and VEGF-A showed overexpression in AML patients compared to normal controls (PAML-non M3 cases. Furthermore, there was a positive correlation between HIF1α and VEGF-A ( P 0.497). Conclusion: Adding to the many studies on the role of hypoxia in solid tumors, our data indicate that HIF1aand VEGF-A overexpression also occurs in AML patients. We consider that this is possibly involved in leukemic cellgrowth and therefore could be a promising target for clinical control.     

Defect of Tumour Necrosis Factor-α (TNF-α) Production and TNF-α-induced ICAM-1 – Expression in BRCA1 Mutations Carriers

Background. Tumour necrosis factor- (TNF-) is a potent cytokine secreted primarily by activated cells from the monocyte/macrophage lineage which exhibits various antitumoral effects including the induction of apoptosis, necrosis, activation of lytic effector cells as well as upregulation of the expression of intercellular adhesion molecule-1 (ICAM-1) which is of decisive importance in the interaction with lymphokine activated killer cells. Previous studies from our laboratory have indicated impaired production of TNF- by monocytes as well as decreased expression of ICAM-1 on monocytes derived from patients with various stages of breast cancer. Methods. In the present experiments, we have assessed spontaneous as well as lipopolysaccharide (LPS)-induced production of TNF- by as well as expression of ICAM-1 on monocytes derived from healthy females with germline mutations of BRCA1 and from healthy age-matched control females. Results. We report that monocytes derived from healthy women with various germline mutations of BRCA1 had significantly decreased spontaneous (p = 0.03) and LPS-induced (p < 0.001) production of TNF-, as compared to monocytes derived from healthy age-matched control females. In contrast, no difference in LPS- or TNF--induced production of interleukin-6 was found. Whereas unstimulated monocytes derived from healthy women with germline mutations of BRCA1 and from healthy control women had similar expression of ICAM-1, stimulation with cytokines TNF- and/or interleukin-1 led to a significant increase of ICAM-1 expression on monocytes derived from control females only, but not from BRCA1 germline mutation carriers (p < 0.001). Conclusion. We conclude that the presence of germline mutations of BRCA1 was associated with a selective deficiency in spontaneous and LPS-induced production of TNF- and of TNF--induced ICAM-1 expression on peripheral blood monocytes.     

小鼠(Mouse)遗传命名规则(1)

1概要小鼠遗传命名标准化国际委员会(International Committee on Standardized Genetic Nomenclature for Mice)关于小鼠命名规则的最新版本是1993年9月通过的。小鼠基因组数据库(The Mouse Genome Database,MGD)(http://www.informatics.jax,org/)基因(基因座)基因全名不用斜     

血清α_1-1-抗胰蛋白酶检测对肺癌临床价值的初步观察(摘要)

为观察血清α-1-抗胰蛋白酶(A_1AT)测定对肺癌的临床价值,我们采用火箭免疫电泳法测定25例肺癌、20例肺良性疾病、42例健康献血员(正常对照)的 A_1AT。三组A_1AT 的 X±SD 分别为470.4±178.9、328.5±191.0、257.1±14.6。肺癌患者血清 A_1AT 非常显著地高于健康人(P<0.01),显著     

Inhibition of hypoxia inducible factor-1α (HIF-1α) decreases vascular endothelial growth factor (VEGF) secretion and tumor growth in malignant gliomas

SummaryIntroduction Hypoxia inducible factor-1α (HIF-1α) regulates vascular endothelial growth factor (VEGF), the presumed principal mediator of angiogenesis in malignant gliomas, under normal physiologic conditions. We examined the effect of HIF-1α on VEGF secretion, tumor growth, and angiogenesis in malignant gliomas.Methods We examined 175 human gliomas for expression of HIF-1α and its downstream-regulated proteins. HIF-1α expression and VEGF secretion in glioma cell lines under normoxia and hypoxia were examined using␣ELISA and Western blot. Malignant glioma cell lines were transfected with dominant-negative HIF-1α (DN-HIF-1α) expression vector or siRNA constructs against the HIF-1α gene. Growth studies were conducted on cells with the highest VEGF/HIF-1α inhibition isolated from stable transfected cell lines. MIB-1-labeling index and microvascular density (MVD) measurements were performed on the in vivo tumors.Results HIF-1 expression correlates with malignant glioma phenotype and was not confined to perinecrotic, pseudopalisading cells. VEGF and HIF-1 expression was high in glioma cell lines even under normoxia, and increased after exposure to hypoxia or growth factor stimulation. Cells transfected with DN-HIF-1α or HIF-1α siRNA demonstrated decreased HIF-1α and VEGF secretion. In vivo but not in vitro growth decreased in response to VEGF and HIF-1 inhibition. HIF-1 siRNA studies showed decreased VEGF secretion and in vitro and in vivo growth of glioma cell lines. MVD was unchanged but MIB-1 proliferation index decreased for both types of HIF-1 inhibition.Conclusions VEGF and HIF-1α are elevated in malignant gliomas. HIF-1α inhibition results in VEGF secretion inhibition. HIF-1α expression affects glioma tumor growth, suggesting clinical applications for malignant glioma treatment.     

食管鳞癌中VEGF_(165b)、HIF-1α的表达及临床意义

目的 检测食管鳞癌组织中VEGF_(165b)和HIF-1α的表达及与临床病理特征的关系.方法 应用免疫组织化学SP法检测143例食管鳞状细胞癌组织中VEGF_(165b)和HIF-1α的表达.结果 VEGF_(165b)和HIF-1α在食管鳞癌组织中的阳性表达率分剔为13.3%和43.4%;VEGF_(165b)阳性表达率与HIF-1α阳性表达率呈负相关关系(P=0.035).HIF-1α阳性表达率与饮酒程度、分期、纵隔淋巴结转移及肿瘤的分化程度呈正相关(P＜0.05).结论 VEGF_(165b)和HIF-1α在食管癌的发生发展和淋巴转移中起重要的作用,VEGF_(165b)的表达与HlF-1α存在相关性,饮酒是食管癌的重要危险因素.VEGF_(165b)可能成为治疗的靶点.     

RNA干扰HIF-1α的表达能抑制宫颈癌血管生成和糖代谢(英文)

Objective:Cervical cancer has become a major public health problem.The development of effective,systemic therapies for cervical cancer is highly desired.We show here that hypoxia inducible factor-1α(HIF-1α) was indicated as an attractive therapeutic molecular target for cervical cancer.Methods:Firstly,we observed the expressional level of HIF-1α in cervical cancer and Hela and Siha cell lines.Secondly,by constructuring HIF-1α shRNA targeting human HIF-1α mRNA common sequence and transfecting it with plasmid...     

Factor inhibiting HIF (FIH-1) promotes renal cancer cell survival by protecting cells from HIF-1α-mediated apoptosis

Background:

Clear cell renal cell carcinoma (CCRCC) is the commonest form of kidney cancer. Up to 91% have biallelic inactivation of VHL, resulting in stabilisation of HIF-α subunits. Factor inhibiting HIF-1 is an enzyme that hydroxylates HIF-α subunits and prevents recruitment of the co-activator CBP/P300. An important question is whether FIH-1 controls HIF activity in CCRCC.

Methods:

Human VHL defective CCRCC lines RCC10, RCC4 and 786–O were used to determine the role of FIH-1 in modulating HIF activity, using small interfering RNA knockdown, retroviral gene expression, quantitative RT–PCR, western blot analysis, Annexin V and propidium iodide labelling.

Results:

Although it was previously suggested that FIH-1 is suppressed in CCRCC, we found that FIH-1 mRNA and protein are actually present at similar levels in CCRCC and normal kidney. The FIH-1 inhibition or knockdown in the VHL defective CCRCC lines RCC10 and RCC4 (which express both HIF-1α and HIF-2α) resulted in increased expression of HIF target genes. In the 786-O CCRCC cell line, which expresses only HIF-2α, FIH-1 attenuation showed no significant effect on expression of these genes; introduction of HIF-1α resulted in sensitivity of HIF targets to FIH-1 knockdown. In RCC4 and RCC10, knockdown of FIH-1 increased apoptosis. Suppressing HIF-1α expression in RCC10 prevented FIH-1 knockdown from increasing apoptosis.

Conclusion:

Our results support a unifying model in which HIF-1α has a tumour suppressor action in CCRCC, held in check by FIH-1. Inhibiting FIH-1 in CCRCC could be used to bias the HIF response towards HIF-1α and decrease tumour cell viability.     

Hypoxia-inducible Factor 1 Alpha (HIF-1α) as a Prognostic Indicator in Patients with Gastric Tumors: A Meta-analysis

Background and Objective: Though researched for years, the prognostic role of hypoxia-inducible factor1 alpha (HIF-1α) in gastric cancer is still controversial. We thus undertook a systematic review to assess therelationship. Method: A systematically literature search of Pubmed, Embase, Web of Science, China BiologicalMedicine Disc and Cochrane Library was undertaken in February 2013, and the reference lists of articles wereretrieved. Results: 12 trials (1,555 participants) were included to assess the association between HIF-1α expressionand survival. Summary hazard ratios (HRs) were calculated. HIF-1α expression was significantly correlatedwith poor overall survival of gastric cancer patients (HR=1.34, 95%CI: 1.13-1.58; P=0.0009), but not with poordisease free survival of gastric cancer patients (HR=1.67, 95%CI: 0.99-2.82; P=0.06). Conclusion: HIF-1α wasassociated with poor OS, but not DFS, especially for Asian patients. But studies evaluating relationships of HIF-1α with OS and DFS in non-Asian gastric cancer patients appear needed.     

肺癌肉瘤(1例报告)

肺癌肉瘤是一少见的恶性混合性肿瘤,1908年kika首先报告。有关鳞癌同恶性纤维组织细胞瘤组合成的肺癌肉瘸,国外文献只见Huszar等报告一例,国内尚未见报告,今报告一例。病史摘要患者男性,60岁,退休工人。因左胸疼痛、咳嗽、咳血3个月,于1983年11月17日入院。患者过去曾在镍矿工作30余年,患过     

细胞周期调控与肿瘤(1)

细胞周期是一个高度有序地运转过程,这种高度有序的运转是通过cyclin/Cdks复合物来实现的.     

ANLL(M5)14年后再发ALL(L1)1例

1 病例介绍 患者，男，60岁。于1985年3月因发热、贫血、轻度脾大首次在我科住院，血象：白细胞28.6×109／L，幼稚细胞68％，血红蛋白65g／L，血小板70×109／L，骨髓象结果：单核细胞系增生极度活跃，原单占15％，幼单占46％，红系、粒系及巨核系均受抑，细胞化学染色结果：POX(+)，NSE(+)，NSE加氟化钠染色(—)。诊断：急性非淋巴细胞白血病M5，经HA等方案化疗获完全缓解，坚……