RNAi抑制PI3Kp85α蛋白活性对人乳腺癌细胞系MCF-7生长抑制的体外研究

目的:探讨敲低PI3Kp85α表达对人乳腺癌细胞系MCF-7细胞生长的影响和机制.方法:用靶向PI3Kp85α的siRNA转染人乳腺癌细胞系MCF-7,使用Real-time PCR法鉴定转染PI3Kp85α表达水平;MTT法评价PI3Kp85α siRNA对乳腺癌细胞系MCF-7生长的影响;流式细胞术检测转染后细胞周期分布和凋亡;采用免疫荧光染色及Western blot方法观察IA型PI3K/AKT通路主要成员的表达.结果:Real-timePCR结果显示PI3Kp85α siR-NA转染导致PI3Kp85α表达下调;MTT结果显示PI3Kp85α siRNA转染抑制肿瘤细胞生长;流式细胞术检测可见PI3Kp85α siRNA转染组细胞周期存在G_0/G_1期阻滞而且凋亡率显著高于对照组与空载体组(F=19.255,P=0.002).结论:应用PI3Kp85α siRNA转染人乳腺癌细胞系MCF-7细胞,可抑制其增殖和诱导细胞凋亡,因此PI3Kp85α可以作为人乳腺癌基因治疗的候选靶点.     

(3)H]-serotonin release from bovine iris-ciliary body: pharmacology of prejunctional serotonin (5-HT(7)) autoreceptors.

In the present study, we investigated the pharmacological characteristics of electrically stimulated [(3)H]-serotonin release from mammalian iris-ciliary bodies. Isolated bovine and human iris-ciliary bodies were loaded with [(3)H]-serotonin, superfused with Krebs buffer solution and then stimulated with trains of 300 direct current (d.c.) pulses to initiate the release of the transmitter. The modification of this [(3)H]-serotonin release process by various serotonergic agonists and antagonists was studied in order to define the pharmacology of serotonin receptor(s) present in the iris-ciliary body. In bovine iris-ciliary body, electrically-evoked [(3)H]-serotonin release was calcium-dependent, tetrodotoxin-sensitive and was enhanced by serotonin (EC(50) = 200 n M) and 5-carboxmidotryptamine (EC(50) = 4 n M). The rank order of potency of agonists in enhancing field-stimulated [(3)H]-serotonin release was: 5-carboamidotryptamine > m-chlorophenylbiguanide > 2-methyl-5-hydroxytryptamine = 5-methoxy-dimethyltryptamine > serotonin > 5-methoxy-tryptamine > L-694,247 = alpha-methyl-5-hydroxytryptamine > CGS 12066A = 8-hydroxy-2-(di- n -propylamino)tetraline. Serotonin and m-chlorophenylbiguanide also enhanced electrically-evoked [(3)H]-serotonin release from human iris-ciliary bodies with EC(50)s of 3 microM and 30 n M, respectively. The pharmacological profile displayed by serotonin receptor agonists was supported by the potent antagonism of the serotonin-induced enhancement of [(3)H]-serotonin release by 5HT(7)receptor antagonists SB-258718 (IC(50) = 18.6 +/- 1.2 nM; n = 4) and mesulergine (IC(50) = 0.26 +/- 0.05 nM; n = 4). However, antagonists at 5HT(6)and 5HT(3)receptors exhibited a relatively weak blockade of serotonin induced enhancement of field-stimulated [(3)H]-serotonin release. These studies have shown the presence of functionally active prejunctional 5HT(7)autoreceptors regulating the release of [(3)H]-serotonin from bovine iris-ciliary bodies. Excitatory prejunctional 5-HT autoreceptors also exist in human iris-ciliary bodies. It is possible that these serotonin autoreceptors may have relevance to the regulation of aqueous humor dynamics in the anterior uvea.     

Effect of Khaya grandifoliola extract on Plasmodium berghei berghei in mice

Khaya grandifoliola stem bark extract was tested for antimalarial action against Plasmodium berghei berghei in mice. The schizontocidal activity of the extract was assessed on early and established infections using chloroquine as a standard drug. The repository activity was also investigated and pyrimethamine was used as the standard. In the early infection test (like the chloroquine group), K. grandifoliola extract was effective in suppressing the malaria infection. However, on the established infection, the extract failed to effectively suppress the infection. The extract also demonstrated residual activity.     

Radio-frequency ablation of renal cell carcinoma in patients who were at significant risk

OBJECTIVE: Although radio-frequency ablation (RFA) has been recently applied as a minimally invasive treatment option for renal cell carcinoma (RCC), indication of this modality remains a critical issue due to the lack of complete tumor destruction as well as the uncertainty of its long-term efficacy. We report the efficacy of RFA for nine carefully selected patients with RCC who had significant reason to avoid invasive surgical treatment under general anesthesia. METHODS: Radio-frequency ablation was performed under epidural or local anesthesia by ultrasound or computed tomography (CT) guidance in nine patients with biopsy proven RCC (mean diameter, 38 mm; range, 20-53 mm), who were at significant operative or anesthetic risk for invasive surgery. Follow-up enhanced CT scans or magnetic resonance images were evaluated every 3-6 months and an evaluation of metastasis was performed every 6 months. RESULTS: At a mean follow-up of 17 months, seven (78%) of the nine patients with renal tumor showed no tumor enhancement. The renal function of all patients was well preserved. All patients were able to continue undergoing their respective treatments for active diseases in other organs in parallel to the RFA treatment. No distant metastasis, urine leakage were reported and one case of temporary hematuria and one case of peri-renal hemorrhage not requiring blood transfusion were encountered. Intra-operative ultrasonography was useful in the real-time monitoring of the minimally excessive extension of ablation into the normal parenchyma. CONCLUSION: Radio-frequency ablation appears to be an effective and safe minimally invasive therapeutic option for selected patients with RCC who have reason to avoid invasive surgery under general anesthesia.     

Dynamics of three-dimensional telomere profiles of circulating tumor cells in patients with high-risk prostate cancer who are undergoing androgen deprivation and radiation therapies

Introduction

Accurate assessment and monitoring of the therapeutic efficacy of locally advanced prostate cancer remains a major clinical challenge. Contrary to prostate biopsies, circulating tumor cells (CTCs) are a cellular source repeatedly obtainable by blood sampling and could serve as a surrogate marker for treatment efficacy. In this study, we used size-based filtration to isolate and enumerate CTCs from the blood of 20 patients with high-risk (any one of cT3, Gleason 8–10, or prostate-specific antigen>20 ng/ml), nonmetastatic, and treatment-naive prostate cancer before and after androgen deprivation therapy (ADT) and radiation therapy (RT).

Role of catalase in pre- and postjunctional responses of mammalian irides to hydrogen peroxide.

In the present study, we examined the effect of inhibition of catalase with 3-aminotriazole (3-AT) on hydrogen peroxide (H2O2)-induced enhancement of sympathetic neurotransmission in bovine irides and on the inhibitory effect of this oxidant on norepinephrine (NE) release from human irides, in vitro. Furthermore, we investigated the effect of 3-AT on H2O2-induced attenuation of contractile responses to carbachol in the bovine isolated irides. Isolated mammalian irides were prepared for studies of [3H]NE release using the superfusion method and for contractile studies using isolated organ baths. At concentrations less than 100 microM, H2O2 had no significant effect on field-stimulated [3H]NE release from bovine or human irides. In bovine irides, 3-AT caused significant (P < 0.001) leftward shifts of concentration-response curves to H2O2 (10-300 microM). 3-AT also increased H2O2-induced attenuation of evoked [3H]NE release from human isolated irides. Low concentrations of H2O2 (< 100 microM) had no effect on carbachol contractions. However, 3-AT unmasked an inhibitory effect of low concentrations of H2O2 (3-100 microM) on carbachol-induced contractions. We conclude that inhibition of catalase causes both pre- and postjunctional responses of isolated mammalian irides to be more susceptible to oxidative stress induced by H2O2.     

用放射吸收法(RA)测量指骨骨密度精确度和准确性的研究

目的 评价放射吸收法(RA)测量2、3、4指骨中节骨密度的精确度和准确性.方法 对19例尸体的双手,用铝制楔型标志物,分别进行了50 kV 400 mA和60 kV 300 mA两次X线照射,对每只手指的第二至第四节指骨的骨矿含量(BMC)和骨密度(BMD),以Au(指骨指数)为单位进行测量和分析.结果 对于BMC-AU来说,这种方法的精密度误差是1.0%,对于BMD-AU来说,精密度误差是0.6%.通过5 mm和6mm 酒精厚度所获得的X射线图可以观察到BMD-Au有2.0%到2.4%的降低,与对照组相比有明显的统计学差异(P<0.01).采用X射线吸收测定法得到的BMC-Au 和前臂的BMC有良好的相关性(r=0.887),并且在指骨的BMC-AU与骨灰重量之间也有较好的相关性(r=0.983).结论 放射吸收法(RA)测量外周骨骨密度具有较高的精确度和准确性.     

Hepatitis B and C in doctors and dentists in Nigeria

We surveyed a random sample (n = 75) of doctors and dentists at University College Hospital, Ibadan, Nigeria. They were offered anonymous testing for hepatitis B surface antigen (HBsAg), hepatitis Be antigen (HBeAG), antibodies to hepatitis B core antigen (anti-HBc) and to hepatitis C virus (anti-HCV), by enzyme immunoassay. The results suggest a high prevalence of hepatitis B virus (HBV) with a high potential of transmissibility, as well as a high prevalence of HCV infection. The majority of the doctors and dentists use universal precaution for protection against viral hepatitis on < 50% of the occasions when they carry out procedures on their patients. Infection with HBV was associated with type of specialty (surgeons, dentists) and lack of HBV vaccination (p < 0.05). After logistic regression, these factors were independently associated with HBV infection (p < 0.05). Sixty (80%) had not received prior HBV vaccination. Unvaccinated personnel were more likely to be surgeons, dentists, < 37 years of age, and have fewer years of professional activity (p < 0.05). After logistic regression, only fewer years of professional activity remained independently associated with lack of vaccination (p < 0.05). To reduce the occupational exposure of HBV, universal precautions must be rigorously adhered to when the doctors and dentists carry out procedures on their patients, and all health-care workers should be vaccinated with HBV vaccine and the HCV vaccine, when it becomes available.