Prostate stem cell antigen (PSCA) expression in human prostate cancer tissues: implications for prostate carcinogenesis and progression of prostate cancer

OBJECTIVE: Prostate stem cell antigen (PSCA) is a recently defined homolog of the Thy-1/Ly-6 family of glycosylphosphatidylinositol (GPI)-anchored cell surface antigens. The objective of the present study was to examine the expression status of PSCA protein and mRNA in clinical specimens of human prostate cancer (PCa) and to validate it as a potential molecular target for diagnosis and treatment of PCa. METHODS: Immunohistochemical (IHC) and in situ hybridization (ISH) analyses of PSCA expression were simultaneously performed on paraffin-embedded sections of 20 benign prostatic hyperplasia (BPH), 20 prostatic intraepithelial neoplasm (PIN) and 48 prostate cancer (PCa) tissues, including 9 androgen-independent prostate cancers. The level of PSCA expression was semiquantitatively scored by assessing both the percentage and intensity of PSCA-positive staining cells in the specimens. We then compared the PSCA expression between BPH, PIN and PCa tissues and analyzed the correlations of PSCA expression level with pathological grade, clinical stage and progression to androgen-independence in PCa. RESULTS: In BPH and low grade PIN, PSCA protein and mRNA staining were weak or negative and less intense and uniform than that observed in high grade PIN (HGPIN) and PCa. Moderate to strong PSCA protein and mRNA expression were noted in 8 of 11 (72.7%) HGPIN and in 40 of 48 (83.4%) PCa specimens examined by IHC and ISH analyses, and their statistical significance was compared with BPH (20%) and low-grade PIN (22.2%) specimens (P < 0.05). The expression level of PSCA increased with a higher Gleason grade, advanced stage and progression to androgen-independence (P < 0.05). In addition, IHC and ISH staining revealed a high degree of correlation between PSCA protein and mRNA overexpression. CONCLUSIONS: Our data demonstrate that PSCA as a new cell surface marker is overexpressed in a majority of cases of human PCa. PSCA expression correlates positively with adverse tumor characteristics, such as increasing pathological grade (poor cell differentiation), worsening clinical stage and androgen-independence and speculatively with prostate carcinogenesis. PSCA may possess prognostic utility and may be a promising molecular target for diagnosis and treatment of PCa.     

Modification of the brain-derived neurotrophic factor gene: a portal to transform mesenchymal stem cells into advantageous engineering cells for neuroregeneration and neuroprotection

Multipotential mesenchymal stem cells (MSCs) are ideal seed cells for recruiting the loss of neural cells due to their strong proliferative capacity, easy acquisition, and considerable tolerance of genetic modifications. After transduction of brain-derived neurotrophic factor (BDNF) gene via recombinant retroviral vectors into the human MSCs, nearly 100% of cells expressed BDNF (which were therefore transformed into BNDF-MSCs) as detected by immunocytochemistry, and the quantity of BDNF in the culture medium was increased by approximately 20,000-fold. In spite of the genomic integration of an exogenous gene, BDNF-MSCs did not present any structural aberration in the chromosomes. All-trans-retinoic acid (RA) induction caused the BDNF-MSCs to differentiate into neural cells with significantly increased expressions of such neural-specific proteins as nestin, NeuN, O4, and glial fibrillary acidic protein (GFAP). The voltage-dependent K+/Ca2+ currents were recorded from the induced BDNF-MSCs using patch-clamp technique. Compared with the MSCs induced by both RA and BDNF, BDNF-MSCs survived in significantly greater number in the induction medium, and also more cells were induced into neuron-like cells (NeuN, P < 0.01) and oligodendrocyte-like cells (O4, P < 0.05). We suppose that, once engrafted into human central nervous system, the BDNF-MSCs would not only recruit the neuronal losses, but also provide, by way of paracrine, large quantities of BDNF that effectively perform the functions of neuroprotection and neuroregeneration, promoting the activation of endogenous neural stem/progenitor cells and their chemotactic migration. On the other hand, the BDNF-MSCs that can survive in the host environment and differentiate subsequently into functional mature cells may also serve as specifically targeting vectors for ex vivo gene therapy.     

三氧化二砷诱导人鼻咽低分化鳞癌BALB/C裸鼠移植瘤的细胞分化和凋亡的研究

目的 探讨三氧化二砷(As2O3)对人鼻咽低分化鳞癌可移植瘤在BALB/C裸鼠体内生长的抑制作用并探讨其机制,重点观察其对鼻咽癌细胞的分化诱导作用。方法 CSNE-1鼻咽癌细胞株接种于裸鼠体内构建移植瘤模型。腹腔注入As2O3(5 mg/kg)。光镜及电镜观察移植瘤的形态学变化,TUNEL染色计算凋亡率,应用免疫组化法检测PCNA,p53,Bcl-2和bax基因的表达。结果 腹腔注射As2O3后,鼻咽癌BALB/C裸鼠移植瘤生长抑制,瘤组织中癌细胞密度减少,细胞皱缩,胞浆红染,瘤组织分化渐成熟,出现角化细胞和角化珠;间质结缔组织增多。透射电镜下肿瘤细胞出现成熟分化及明显角质化,细胞表面微小突起增多,细胞间桥粒增多并以桥粒互相连接,细胞核浆比例减少,胞浆中出现大量张力原纤维并围绕核周。TUNEL检查提示凋亡细胞增多;用药 后野生型p53及baX高表达,PCNA低表达,Bcl-2无变化。 结论As2O3能诱导人低分化鼻咽裸鼠移植瘤分化和凋亡,可能与p53及bax高表达相关,与Bcl-2无关。     

Reactive oxygen species and antioxidants in apoptosis of esophageal cancer cells induced by As2O3

To explore the relationship between the reactive oxygen species (ROS) and apoptosis in esophageal carcinoma cells (SHEE85) induced by arsenic trioxide (As2O3), we focused on changes of apoptosis, ROS, and antioxidants. Apoptosis of SHEE85 was confirmed by means of DNA fragmentation stained by Hoechst 33342, Sub-G1 cells scored by flow cytometry and ultrastructure of cells by electron microscopy. To evaluate the level of ROS, the chemiluminescent method was used for measuring the production of superoxide anion (O(-)*2). Lipid peroxide (malondialdehyde, MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured respectively by the photometry method. In the cells treated with As2O3 at a concentration of 5.0 micromol/l for 2-24 h, the content of cellular O(-)*2 and MDA was increased, but SOD and GSH-Px were significantly lower in the process of apoptosis in SHEE85. As2O3 at concentration of 0.5 micromol/l did not cause cell apoptosis but promoted cell proliferation. These results suggest that As2O3 at a high dosage (5 micromol/l) causes cell apoptosis and at a low dosage (0.5 micromol/l) causes cell proliferation. The essential mechanisms of cell apoptosis induced by As2O3 may be related to the increase of ROS and decrease of anti-oxidation. ROS and antioxidants participate in the apoptotic pathway of esophageal carcinoma cells.     

Argyrophilic nuclear organizer regions in nasopharyngeal carcinoma and paraneoplastic epithelia

BACKGROUND: Nucleolar organizer regions (NORs), which are loops of DNA containing ribosomal RNA genes, have been shown to correlate with cell proliferation and malignant transformation. The diagnostic value of silver staining NORs (AgNORs) in preneoplastic epithelia and nasopharyngeal carcinoma (NPC) by the quantitative assessment of AgNORs proteins is evaluated. METHODS: Silver-staining of NORs was applied to 70 paraffin sections of NPC biopsy specimens, including 29 samples of the adjacent normal glandular epithelia (GE), 19 hyperplastic/dysplastic columnar epithelia (CE) in the adjacent mucosa, 10 hyperplastic/dysplastic squamous epithelia (SE) in the adjacent mucosa, 54 differentiated nonkeratinizing carcinoma (DC), and 16 undifferentiated carcinoma (UC). The morphometric features of AgNORs in preneoplastic epithelia and cancer cells were analyzed by image cytometric analysis and then compared. RESULTS: The AgNOR count, mean AgNOR area, and AgNOR area-count ratio increased significantly from GE to CE to DC or UC. The mean nuclear area, AgNOR area, and AgNOR area-count ratio increased significantly from GE to SE to UC, whereas overlapping AgNOR values were observed between SE and DC. UC had significantly higher values than DC in mean nuclear area, AgNOR area, and AgNOR area-count ratio. CONCLUSIONS: The morphometric analysis of AgNORs reflected cell proliferative activity and histologic differentiation of tumor rather than malignant transformation in different nasopharyngeal epithelia and NPC. AgNOR area and AgNOR area-count ratio are the most valuable features for differential diagnosis of normal, preneoplastic, and cancer cells.     

IL-6及其受体与炎症性疾病关系的新进展

白细胞介素-6（IL-6）作为前炎症细胞因子，在炎症反应过程中起着重要的作用。IL-6的生物学功能只有通过和其受体形成IL-6／IL-6R／gp130复合体才能进行信号转导从而发挥作用。随着其受体信号传递途径研究的不断深入，IL-6受体有望成为一个有效的治疗靶点，在炎症性疾病治疗过程中发挥作用。本文就其在炎症性痰病方面的研究进展做一综述。     

新生儿肺出血高危因素及早期诊断的临床分析

目的:探讨新生儿肺出血的危险因素和早期诊断方法。方法:回顾性研究新生儿肺出血56例,分析高危因素及早期诊断方法。结果:56例肺出血的新生儿,早产、低体重、男婴发生率分别为58.93%、71.43%、76.79%,是生理性高危因素;原发病中重度窒息、感染、肺透明膜病、硬肿症、胎粪吸入综合征、肺动脉高压、先天性心脏病、胆红素脑病发生率分别为30.36%、19.64%、14.29%、12.5%、8.93%、7.14%、3.57%、3.57%,是病理性高危因素。肺出血前30 m in~4 h其临床症状和体征均有明显改变。有肺部湿罗音与无肺部湿罗音高危因素比较无显著性差异,但在死亡数及出现肺出血至死亡时间比较有显著性差异(P<0.05)。提示具有相同的危险因素,无肺部湿罗音进展及死亡均更快。气管插管行气管内吸引与口鼻涌血诊断肺出血在肺出血时间、死亡数、治愈数比较有显著性差异(P<0.05),气管内吸引更能早期发现,避免误诊,有助于及时治疗。结论:有严重原发病的高危新生儿出现紫绀苍白加重、呼吸心率改变、肺部湿罗音出现或增多、气管插管吸出血性痰可早期诊断肺出血,早期诊断是提高治疗效果的关鍵。     

自制牵引架在治疗手指骨骨折中的临床应用

目的 评价自制牵引架在手部指骨骨折中的治疗效果.方法 对11例(共19指)手部指骨新鲜闭合性骨折,采取闭合整复自制牵引架治疗21～28 d(平均24 d),术后平均随访2～6个月,从患手的关节活动范围和影像学检查进行疗效评价.结果 术后X线片显示所有骨折均解剖复位,平均24 d去除自制牵引架.1例患者1个手指出现针道感染.11例(19指)骨折患者均已骨性愈合,患者手指的关节活动范围恢复正常,均已恢复原来的工作.结论 自制牵引架技术是治疗新鲜闭合性指骨不稳定骨折的有效方法.     

甲亢及其治疗与病毒性肝炎互相影响临床分析

目的:研究甲状腺机能亢进症及抗甲亢治疗对病毒性肝炎肝脏功能的影响,病毒性肝炎肝脏功能对甲亢的影响。方法:选择单纯病毒性肝炎48例,单纯甲亢45例及甲亢合并病毒性肝炎38例,分别比较各组肝功能及甲状腺功能情况,并比较抗甲亢治疗与未抗甲亢治疗对甲亢合并病毒性肝炎患者肝功能恢复的影响,及病毒性肝炎对甲亢的影响。结果:甲亢合并病毒性肝炎肝功能损害比单纯甲亢及单纯病毒性肝炎都明显,且有显著性差异(P<0.05),抗甲亢治疗能改善甲亢合并病毒性肝炎患者肝功能的恢复,甲亢合并病毒性肝炎比单纯甲亢血中T3、T4升高明显,导致甲亢加重。结论:甲亢能加重病毒性肝炎肝功能损害,抗甲亢治疗对甲亢合并病毒性肝炎患者肝功能的恢复是安全有效的。     

贲门癌家族易感性相关因素的初步探讨

目的探讨广东省汕头地区贲门癌家族易感性的相关因素。方法收集我院１９９０年１月至１９９７年１２月手术切除贲门癌５６４例,对有家族性肿瘤史的５０例贲门癌患者及其亲属患癌者进行调查分析。结果贲门癌的发病存在家族遗传易感性,有家族癌史的患者占８．９％,平均发病年龄５６．５岁。结论贲门癌家族易感性可能与遗传因素、环境因素和家族免疫功能缺陷有关,应予足够重视。