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.     

Enhanced magnetic auditory steady-state response in early Alzheimer's disease.

OBJECTIVE: Previous studies have reported abnormalities in both spontaneous and evoked electromagnetic brain activity in Alzheimer's disease (AD). We studied the auditory steady-state response (SSR) which represents the net effect of entrained background activity and superimposed cortical evoked responses, in AD patients and healthy controls. METHODS: Whole-head magnetoencephalography (MEG) was used to measure SSR to monaural 40-Hz stimulation in AD patients and age-matched controls. Equivalent current dipoles (ECD) of the SSR were modeled in each hemisphere, and source amplitudes were compared between the two groups using time-varying ECD models. RESULTS: Our results indicate that the SSR is significantly increased in AD patients with mild to moderate cognitive deterioration in comparison with healthy elderly subjects. CONCLUSIONS: Goal-directed functioning requires optimization of inhibitory and excitatory inputs in the cortex, allowing the adaptation of responsiveness to repetitive stimulation with low relevance. The present results suggest that this balance is impaired in AD, manifesting itself in decreased inhibition in cortical auditory processing and impaired adaptation of the stimulus-locked activity, probably due to abnormalities in cholinergic modulation. SIGNIFICANCE: MEG appears to be a sensitive tool to detect abnormalities of auditory processing already in early stages of AD.     

Norfin in oncological practice]

A synthetic opiate agonist-antagonist norphin (buprenorphin) has been studied in 297 cancer patients as an analgetic component of general anesthesia, in postoperative analgesia and in the treatment of chronic pain syndrome. In modified neuroleptanalgesia based on norphin, diazepam, droperidol and N2O the patient is more adequately prevented from surgical trauma than in conventional neuroleptanalgesia based on fentanyl. This is confirmed by greater stability in circulation, metabolism and stress hormone parameters, however this anesthesia technique is less manageable and may be accompanied by prolonged postanesthesia depression of the central nervous system. Good results have been obtained when norphin pills were used sublingually for the treatment of long-lasting intensive chronic pain syndrome in incurable cancer patients. Norphin is no less effective than morphin, however, unlike morphin, it causes no severe adverse reactions.     

Magnetoencephalographic evidence of abnormal auditory processing in amyotrophic lateral sclerosis with bulbar signs.

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is characterized by progressive motor neuron damage that gives rise to muscle denervation. Besides motor neuron damage, conscious auditory processing appears to be impaired in ALS, whereas it has remained ambiguous whether preceding automatic auditory processing is abnormal in ALS and specifically in ALS with bulbar signs. METHODS: Auditory evoked fields (AEFs) to monaurally presented frequent and infrequent tones with stimulus intervals of 500 and 2500 ms were recorded with magnetoencephalography (MEG) from 10 ALS patients having bulbar signs and from 10 age-matched healthy subjects. RESULTS: The amplitudes of the P50m and N100m responses, which index automatic auditory processing underlying stimulus detection, were significantly increased and P50m latency was shortened in ALS patients. MMNm, which reflects memory-based auditory comparison process, was increased in amplitude in the patient group, whereas the MMNm latency was similar in both groups. AEF latency and amplitude values failed to correlate with the severity of ALS as measured by ALS Functional Rating Scale (ALSFRS). CONCLUSIONS: The present results suggest that auditory processing underlying stimulus detection, and subsequent memory-based comparison processes are abnormal in ALS patients with severe bulbar signs. This might be due to cortical overactivity of excitatory neurotransmitter glutamate observed in ALS.     

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.     

Significant relationship of time-dependent uroflowmetric parameters to lower urinary tract symptoms as measured by the International Prostate Symptom Score

AIMS: The aim of the present paper is to elucidate the possible involvement of time-dependent parameters as obtained by uroflowmetry in the manifestation of lower urinary tract symptoms (LUTS) in elderly patients. METHODS: Using simple and multiple regression analyses, the correlation of the International Prostate Symptom Score (IPSS) with objective parameters including age, postvoid residual, uroflowmetry and transrectal ultrasonic measurements of the prostate was analyzed in 206 male patients (average age of 68.0 +/- 7.4 years) who visited our outpatient clinic complaining of LUTS. RESULTS: In the 206 patients, the mean maximum flow rate was 12.2 mL/s (13.7 mL/s in mild, 11.9 mL/s in moderate, and 11.2 mL/s in severe IPSS total score) and average flow rate was 4.4 mL/s (5.4 mL/s in mild, 4.3 mL/s in moderate, and 3.5 mL/s in severe IPSS total score). Simple regression analyses demonstrated that age, voiding time, and average and maximum flow rates correlate significantly with symptom scores. In particular, relatively strong relationships were found between average flow rate and scores of intermittency, weak stream and total and voiding symptoms scores. Serum prostate specific antigen level, postvoid residual and prostatic ultrasonic measurements did not show a significant correlation with symptom scores. Multiple regression analyses revealed age and average flow rate to be independent determinants for symptom scores. These results suggest that the time-dependent function in micturition interferes in the manifestation of LUTS in elderly men who have borderline or pathologic maximum flow rate. When evaluating uro flowmetry in elderly male patients with LUTS, attention should be paid to time-dependent parameters such as voiding time and average flow rate.     

Proliferative response of cultured Nb2 rat lymphoma cells to human serum prolactin and growth hormone

Human prolactin and growth hormone induce specific proliferative responses in a culture of Nb2 rat lymphoma cells. These responses can be employed for characterization of the activity of serum immunoreactive prolactin and growth hormone in patients with endocrine disorders. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 11, pp. 559–563, November, 1996