Cyclooxygenase inhibitors in urinary bladder cancer: in vitro and in vivo effects

More than 14,000 people die from invasive transitional cell carcinoma (TCC) of the urinary bladder yearly in the United States. Cyclooxygenase (COX)-inhibiting drugs are emerging as potential antitumor agents in TCC. The optimal in vitro or in vivo systems to investigate COX inhibitor antitumor effects have not been defined. The purpose of this study was to determine COX-1 and COX-2 expression and antitumor effects of COX inhibitors in human TCC cell lines (HT1376, RT4, and UMUC3 cells) and xenografts derived from those cell lines. COX-2 expression (Western blot, immunocytochemistry) was high in HT1376, modest in RT4, and absent in UMUC3 cells in vitro. Similarly, COX-2 expression was noted in RT4 but not UMUC3 xenografts. COX-2 expression in HT1376 xenografts was slightly lower than that observed in vitro. None of four COX inhibitors evaluated (celecoxib, piroxicam, valeryl salicylate, and NS398) reduced TCC growth in standard in vitro proliferation assays at concentrations that could be safely achieved in vivo (< or =5 micromol/L). Higher celecoxib concentrations (> or =50 micromol/L) inhibited proliferation and induced apoptosis in all three cell lines. Celecoxib or piroxicam treatment in athymic mice significantly delayed progression of HT1376 xenografts, which express COX-2, but not UMUC3 xenografts that lack COX-2 expression. In conclusion, standard in vitro assays were not useful in predicting COX inhibitor antitumor effects observed in vivo. Athymic mice bearing TCC xenografts provide a useful in vivo system for COX inhibitor studies. Results of this study provide justification for further evaluation of COX inhibitors as antitumor agents against TCC.     

肿瘤切除联合胆道支架及粒子植入治疗肝门区胆管癌的手术配合

肝门区胆管癌分为胆囊癌和胆管细胞型原发性肝癌 ,后者对肝门影响小。其特点是发现晚、转移早、症状不典型 ,手术切除率低 ,对放疗、化疗等不敏感[1 ,2 ] 。 5年生存率 2 %～ 3 %,绝大部分病人 1年内死亡。目前手术仍是提高该类肿瘤治疗效果的希望 ,但手术后有胆道狭窄和复发等问题。我院在 2 0 0 4年采用肿瘤切除联合胆道支架、粒子植入治疗肝门区胆管癌 11例 ,解决了经典手术切除率低 ,术后胆道狭窄、梗阻、肿瘤易复发等问题 ,获得了满意的疗效 ,现报告如下。1　临床资料　　胆管细胞型原发型肝癌 7例 ,病变肝胆管受侵范围以改良BISMUT…     

广东粤西地区汉族人群红细胞酸性磷酸酶-腺苷脱氨酶-腺苷酸激酶的遗传学特性

目的:应用红细胞酸性磷酸酶-腺苷脱氨酶-腺苷酸激酶同步电泳分型,从血型遗传学角度对粤西汉族血液中3种酶型的表型分布、基目频率进行调查。方法:实验于2005-03/11在湛江师范学院完成。①血样取自广东湛江地区无血缘关系的汉族健康成人120例,3代内无与外族通婚史。②120例汉族健康成人均取耳血一两滴,渗于无菌纱布上,血痕直径1cm,低温干燥保存,7～14d内进行血痕表型检测。③基因频率计算采用Hardy-Weinbery平衡计算法。种群中某基因频率(%)=种群中该基因总数/种群中该对等位基因总数×100%;种群中某基因型频率(%)=种群中该基因型个体数/该种群的个体数×100%。结果:实验血样取自广东湛江地区无血缘关系的汉族健康成人120例,全部进入结果分析。①粤西汉族酸性磷酸酶、腺苷脱氨酶、腺苷酸激酶3种酶型表现型的观察值与期望值基本吻合(P>0.05),检测的酶型中未发现稀有型、变异型,亦未发现罕见基因。②在粤西汉族群体中,酸性磷酸酶具有中高鉴别能力(积累能力值0.5043),腺苷脱氨酶为低鉴别能力(积累能力值0.2922),而腺苷酸激酶无鉴别能力(积累能力值0.0023)。结论:粤西汉族人群3种检测酶型中未发现稀有型、变异型,亦未发现罕见基因。符合Hardy-Weinbery遗传平衡定律。     

Synergistic Inhibition on Acetylcholinesterase by the Combination of Berberine and Palmatine Originally Isolated from Chinese Medicinal Herbs

Alzheimer’s disease is a multi-factorial neurodegenerative disorder devastatingly affecting the aged population worldwide. Previous studies have shown that medicinal herbs used in traditional Chinese medicine might be benefit to Alzheimer’s disease patients. Berberine and palmatine, two isoquinoline alkaloids found in several medicinal herbs, were used for memory enhancement in China. In this study, the inhibitory effects of combined berberine and palmatine on acetylcholinesteras were evaluated using recombinant human acetylcholinesterase. Our results showed that the combination of berberine and palmatine inhibited acetylcholinesterase in a mixed competitive pattern. By the median-effect principle, the calculated combination index of the combination was less than 1, suggesting that berberine and plamatine inhibited acetylcholinesterase synergistically. Furthermore, the drug-reducing index of berberine and palmatine were 2.98 and 2.66, respectively. Taken together, the results showed that the combination of the two alkaloids might potentially be developed as a more effective therapeutic strategy for Alzheimer’s disease patients.     

Management of Positive Sub‐areolar/Nipple Duct Margins in Nipple‐Sparing Mastectomies

We evaluated management of positive sub‐areolar/nipple duct margins in nipple‐sparing mastectomies (NSM) at our institution. Retrospective chart review of all NSM from January 2007 to April 2012 was performed and patient, tumor, and treatment information was collected. Sub‐areolar/nipple duct margins included ductal tissue from within the nipple. Of 438 NSM, 22 (5%) had positive sub‐areolar/nipple duct margins; 21 of 220 cancer‐bearing breasts (10%) and 1 of 218 prophylactic mastectomies (0.5%). Positive margins included four with invasive lobular carcinoma and 18 with ductal carcinoma in situ (DCIS). Management included removal of eight nipples and nine nipple areola complexes (NAC). Four of 17 nipple/NAC specimens had evidence of residual DCIS and none had residual invasive cancer. The majority of nipple/NAC specimens excised for a positive margin had no residual malignancy. Future studies are needed to determine the extent of NAC tissue removal required for positive margins.     

Detection of deception based on fMRI activation patterns underlying the production of a deceptive response and receiving feedback about the success of the deception after a mock murder crime

The ability of a deceiver to track a victim’s ongoing judgments about the truthfulness of the deceit can be critical for successful deception. However, no study has yet investigated the neural circuits underlying receiving a judgment about one’s lie. To explore this issue, we used a modified Guilty Knowledge Test in a mock murder situation to simultaneously record the neural responses involved in producing deception and later when judgments of that deception were made. Producing deception recruited the bilateral inferior parietal lobules (IPLs), right ventral lateral prefrontal (VLPF) areas and right striatum, among which the activation of the right VLPF contributed mostly to diagnosing the identities of the participants, correctly diagnosing 81.25% of ‘murderers’ and 81.25% of ‘innocents’. Moreover, the participant’s response when their deception was successful uniquely recruited the right middle frontal gyrus, bilateral IPLs, bilateral orbitofrontal cortices, bilateral middle temporal gyrus and left cerebellum, among which the right IPL contributed mostly to diagnosing participants’ identities, correctly diagnosing 93.75% of murderers and 87.5% of innocents. This study shows that neural activity associated with being a successful liar (or not) is a feasible indicator for detecting lies and may be more valid than neural activity associated with producing deception.