Differentiating agents facilitate infection of myeloid leukemia cell lines by monocytotropic HIV-1 strains [published erratum appears in Blood 1991 Apr 1;77(7):1624]

Monocytotropic human immunodeficiency virus type 1 (HIV-1) isolates from patients with acquired immunodeficiency syndrome (AIDS) infect mononuclear phagocytes as well as activated T cells, but do not usually infect immature human myeloid cell lines in vitro. The HL-60 promyelocytic/myeloblastic cell line and the promonocytic line, U937, were susceptible to productive infection by monocytotropic HIV-1 isolates (HIV-1JR-FL and HTLV-IIIBa-L) after treatment with retinoic acid, dimethyl sulfoxide, dibutyryl cAMP, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), or 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Virus production was only detected when these compounds were added before virus infection. Virus replication did not correlate with CD4 receptor expression because undifferentiated HL-60 cells express CD4 and the level of CD4 expression did not increase after differentiation in the presence of retinoic acid, 1,25(OH)2D3, or TPA. A mature monocytic cell line (THP-1) was capable of infection without pretreatment, and treatment with differentiating agents enhanced virus production. A chronically infected cell line (J-HL-60) was isolated after HIV-1JR-FL infection of HL-60 cells treated with retinoic acid. Virus production in this cell line was enhanced more than 10-fold after differentiation in the presence of 1,25(OH)2D3 or TPA. The majority of virus production by 1,25(OH)2D3-treated J-HL-60 cells was associated with the mature, adherent population. Molecular analysis of a cloned line of J-HL-60 showed integration of a single DNA provirus. These results suggest that cellular factors associated with precursor cell differentiation along the myelomonocytic pathway are required for optimal replication of monocytotropic HIV-1 strains in vitro.     

组织工程化的雪旺细胞在视神经损伤修复中的应用

0 引言 视神经损伤(optic nerve injury)是常见的眼外伤类型,临床上常见各种面部及颅脑外伤如压迫、牵伸、撕裂、切断等原因致使视神经走行的某一段受损,如果治疗不及时可能造成患者视功能不可逆性的丧失.     

血管内皮生长因子与基质金属蛋白酶2在血管瘤不同生长过程中的表达特征

目的:观察血管内皮生长因子与基质金属蛋白酶2在血管瘤不同分期中的表达。方法:取自承德医学院附属医院1998-01/2005-12期间血管瘤手术切除的标本共60例及正常带血管皮肤手术切除标本10例,患者家属知情同意。①实验分组:根据Mulliken标准进行病理诊断并分类,所有标本共分4组。增生组22例;退化组20例;退化完成组18例。另取10例正常带血管皮肤组织作为对照组。②采用免疫组织化学S-P法对各组标本的血管内皮生长因子、基质金属蛋白酶2进行染色。③实验评估:以正常血管上皮细胞或肿瘤细胞胞浆出现棕黄色颗粒为阳性,检测各组血管内皮生长因子与基质金属蛋白酶2的表达。结果:①随着血管瘤病理时期的变化,血管内皮生长因子与基质金属蛋白酶2出现明显不同的表达。②增生组血管内皮生长因子与基质金属蛋白酶2的阳性表达率明显高于其他各组,且随着血管瘤的退化,两者的阳性表达率逐渐下降,至退化完成期时与对照组几乎无差别。③血管内皮生长因子与基质金属蛋白酶2的表达呈正相关。结论:血管内皮生长因子与基质金属蛋白酶2在血管瘤的不同分期中起重要作用,其表达水平与血管瘤的病理分期有密切关系。     

cis-Retinoic acid stimulates the clonal growth of some myeloid leukemia cells in vitro

We studied the effects of cis-retinoic acid (cisRA) on the clonogenic growth of samples of leukemic cells from 35 patients with acute nonlymphocytic leukemia (ANLL). We observed significant inhibition of leukemic colony growth in 17 samples by 10(-7) to 10(-6)M cisRA. However, we found that retinoid exposure resulted in striking stimulation of clonal growth in ten samples at the same drug concentrations. With the exception of cases with promyelocytic features, there was no morphologic or functional evidence that cisRA induced the leukemic blasts to differentiate. Both inhibition and stimulation were dose-dependent and observable at pharmacologically achievable levels of cisRA. Leukemic cells with monocytic features more frequently demonstrated a stimulatory response than did those without monocytic features. Depletion of T lymphocytes and monocytes did not alter the type of growth response. Assays for cellular retinoic acid- binding protein (CRABP) were performed on five samples (two with inhibitory growth responses, two with stimulatory responses, and one with no growth) and failed to reveal detectable levels of CRABP in any case. The addition of cisRA to liquid suspensions of leukemic cells produced no significant change in the number of viable cells. We conclude that the effects of cisRA on leukemic colony growth are not cytotoxic and not mediated by T lymphocytes, monocytes, or CRABP. More importantly, cisRA appears to enhance the growth of certain human leukemia cells in vitro. Taking into account the increasing use of retinoids in clinical trials for patients with leukemia, the latter findings may represent a significant cautionary note.     

A Phase II trial of the oral mTOR inhibitor everolimus in relapsed Hodgkin lymphoma

Everolimus is an oral antineoplastic agent that targets the raptor mammalian target of rapamycin (mTORC1). The phosphatidylinositol 3‐kinase/mTOR signal transduction pathway has been demonstrated to be activated in tumor samples from patients with Hodgkin lymphoma (HL). The goal of this trial was to learn the antitumor activity and toxicity of everolimus in patients with relapsed/refractory HL. Patients were eligible if they had measurable disease, a platelet count >75,000, and an absolute neutrophil count >1,000. Patients received everolimus 10 mg PO daily. Dose reductions were allowed. Response was assessed after two and six cycles and then every three cycles until progression. Patients could remain on drug until progression or toxicity. Nineteen patients were enrolled. Median age was 37 years (range, 27–68). Patients had received a median of six prior therapies (range, 3–14) and 84% had undergone prior autologous stem cell transplant. The ORR was 47% (95% CI: 24–71%) with eight patients achieving a PR and one patient achieving a CR. The median TTP was 7.2 months. Four responders remained progression free at 12 months. Patients received a median of seven cycles of therapy. Of the 19 patients, one remains on therapy at 36 months; the others went off study because of progressive disease (16), toxicity (1), and death from infection (1). Four patients experienced a Grade 3 or higher pulmonary toxicity. Everolimus has single‐agent activity in relapsed/refractory HL and provides proof‐of‐concept that targeting the mTOR pathway in HL is clinically relevant. Am. J. Hematol., 2010. © 2010 Wiley‐Liss, Inc.     

Cerebral astroblastoma radiologically mimicking pilocytic astrocytoma: A case report

Astroblastoma is a rare central nervous system tumor. We reported a case of a 24‐year‐old Nepalese woman with radiological features mimicking pilocytic astrocytoma which came out to be low‐grade astroblastoma in histopathological and immunohistochemistry examination after total excision of the tumor.