Sacituzumab govitecan: breakthrough targeted therapy for triple-negative breast cancer

Introduction: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with an increased risk of recurrence and cancer-related death. Unlike hormone receptor-positive or HER2-positive breast cancers, there are limited targeted therapies available to treat TNBC and cytotoxic chemotherapy remains the mainstay of treatment. Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate targeting Trop-2 expressing cells and selectively delivering SN-38, an active metabolite of irinotecan.

Areas covered: This review covers the mechanism of action, safety and efficacy of sacituzumab govitecan in patients with previously treated, metastatic TNBC. Additionally, efficacy data in other epithelial malignancies is included based on a PubMed search for ‘sacituzumab govitecan’ and ‘clinical trial’.

Expert opinion: Sacituzumab govitecan has promising anti-cancer activity in patients with metastatic TNBC previously treated with at least two prior lines of systemic therapy based on a single arm Phase I/II clinical trial. A confirmatory Phase III randomized clinical trial is ongoing. Sacituzumab govitecan has a manageable side effect profile, with the most common adverse events being nausea, neutropenia, and diarrhea. The activity of sacituzumab govitecan likely extends beyond TNBC with promising early efficacy data in many other epithelial cancers, including hormone receptor-positive breast cancer.     

Deformational posterior plagiocephaly: diagnosis and treatment.

OBJECTIVE: This study was designed to evaluate the effectiveness of helmet therapy (DOC band) in the correction of patients with moderate to severe posterior deformational plagiocephaly. DESIGN: In this prospective study, the infants were evaluated using 18 anthropometric measurements. PATIENTS: The charts of 248 patients seen between August 1, 1995, and July 31, 1999, were reviewed, and 125 met the criteria for inclusion in the study. All the patients had posterior deformational plagiocephaly with no other craniofacial deformities or medical conditions. Treatment was instituted prior to 1 year of age, and all patients were compliant with DOC band usage and had complete anthropometric measurements. RESULTS: The study recorded a 41.56% (p < .001) reduction in cranial vault asymmetry and a 40.23% (p <.001) reduction in cranial base asymmetry. Orbitotragial asymmetry was improved 18.72% (p = .0738). The age at which treatment was begun was not a significant factor in predicting treatment outcomes.     

The synthetic caged garcinia xanthone cluvenone induces cell stress and apoptosis and has immune modulatory activity

Several caged Garcinia xanthone natural products have potent bioactivity and a documented value in traditional Eastern medicine. Previous synthesis and structure activity relationship studies of these natural products resulted in the identification of the pharmacophore represented by the structure of cluvenone. In the current study, we examined the anticancer activity of cluvenone and conducted gene expression profiling and pathway analyses. Cluvenone was found to induce apoptosis in T-cell acute lymphoblastic leukemia cells (EC?? = 0.25 μmol/L) and had potent growth-inhibitory activity against the NCI60 cell panel, including those that are multidrug-resistant, with a GI?? range of 0.1 to 2.7 μmol/L. Importantly, cluvenone was approximately 5-fold more potent against a primary B-cell acute lymphoblastic leukemia compared with peripheral blood mononuclear cells from normal donors, suggesting that it has significant tumor selectivity. Comparison of cluvenone's growth-inhibitory profile to those in the National Cancer Institute database revealed that compounds with a similar profile to cluvenone were mechanistically unlike known agents, but were associated with cell stress and survival signaling. Gene expression profiling studies determined that cluvenone induced the activation of mitogen-activated protein kinase and NrF2 stress response pathways. Furthermore, cluvenone was found to induce intracellular reactive oxygen species formation. Lastly, the modulation in the expression of several genes associated with T cell and natural killer cell activation and function by cluvenone suggests a role as an immune-modulator. The current work highlights the potential of cluvenone as a chemotherapeutic agent and provides support for further investigation of these intriguing molecules with regard to mechanism and targets.     

应用功能磁共振成像分析脑卒中患者康复治疗前后大脑再塑机制

目的:应用功能磁共振成像观察脑卒中后及康复过程中,在相应脑内运动功能区激活的变化情况,探讨不同运动模式下皮质功能再塑的表现。方法:选取2003-02/10大庆油田总医院康复科住院的皮质下脑梗死患者8例,在发病后1周始进行连续两个月的康复。在康复前、康复1,2个月时运用Brunnstrom分级、Caroll上肢功能量表(0￣100分,评分越高功能越好)对其手功能进行评价,并采用GEMR/iHiSpeed1.5超导磁共振扫描机进行磁共振成像功能激发检查。患者用病手执行简单运动(快速连续的拇指与其他各指的对指动作)、随意运动(用病手摸不同形状的木块),获得脑功能激发图像,观察脑内相关功能区的激活情况。结果:8例受试者均进入结果分析。①康复后所有患者Brunnstrom分级和Caroll上肢功能评分均较康复前有明显改善。②病手简单运动时脑内相关功能区的激活情况:8例受试者7例在损伤后早期手指不能对指,所以没有激活;M1,SMA,PMA脑区和小脑呈现单侧激活-双侧激活-单侧激活的变化过程;随着运动功能恢复,脑内激活数目随时间呈下降趋势,几乎接近正常人脑功能表现。③病手随意运动时脑内相关功能区的激活情况:实验中发现引起的运动相关功能区的激发情况变化多样,规律性较差,但其中5例受试者表现出损伤后激发数目明显减少,许多对运动起决定性支配作用的功能区亦不激活;随着运动功能恢复,激发区数目呈上升趋势,同损伤后简单运动的激活表现。结论:①脑卒中后病手经过康复治疗简单运动恢复较好,康复治疗2个月后脑内运动功能相关区域激活的规律已同正常人。②脑卒中后病手随意运动恢复较困难,康复治疗后不如简单运动恢复好,脑内相关运动功能区激活无明显的规律性。随着运动功能的恢复,脑内相应的运动功能区激活增多。     

Reducing overdiagnosis by polygenic risk-stratified screening: findings from the Finnish section of the ERSPC

Background:

We derived estimates of overdiagnosis by polygenic risk groups and examined whether polygenic risk-stratified screening for prostate cancer reduces overdiagnosis.

Methods:

We calculated the polygenic risk score based on genotypes of 66 known prostate cancer loci for 4967 men from the Finnish section of the European Randomised Study of Screening for Prostate Cancer. We stratified the 72 072 men in the trial into those with polygenic risk below and above the median. Using a maximum likelihood method based on interval cancers, we estimated the mean sojourn time (MST) and episode sensitivity. For each polygenic risk group, we estimated the proportion of screen-detected cancers that are likely to be overdiagnosed from the difference between the observed and expected number of screen-detected cancers.

Results:

Of the prostate cancers, 74% occurred among men with polygenic risk above population median. The sensitivity was 0.55 (95% confidence interval (CI) 0.45–0.65) and MST 6.3 (95% CI 4.2–8.3) years. The overall overdiagnosis was 42% (95% CI 37–52) of the screen-detected cancers, with 58% (95% CI 54–65) in men with the lower and 37% (95% CI 31–47) in those with higher polygenic risk.

Conclusion:

Targeting screening to men at higher polygenic risk could reduce the proportion of cancers overdiagnosed.     

织构复合水凝胶体系的假说

生物软组织可视为具有多层次结构的织构复合水凝胶体系(TCHS)、以水凝胶复合元件(HCE)为基本的构件(CP),通过一定的组合、排列方式构筑一系列多层次结构的不同软组织。软组织中任何层次的结构单元既可视为织构复合水凝胶体系又可视为构件。任何层次的TCHS中,构件的结构及其组合排列方式决定着该层次单元的功能。以织构复合水凝胶体系的观点考察了真核细胞、角膜和骨骼肌的多层次结构。双层网络水凝胶、皮芯复合水凝胶纤维人工肌肉模型、时空匹配可降解细胞支架等研究成果初步地证明了提出织构复合水凝胶体系观点的合理性。     

普通男大学生关节相对峰力矩与蹲跳高度的关联分析

目的:分析普通男大学生髋、膝、踝、肩、肘各关节相对峰力矩与蹲跳高度的相关性。方法:实验于2004-11/2005-01在河北省体科所完成。①实验对象:随机抽取河北省某大学普通男生30名,年龄(21.8±0.8)岁,身高(170.67±5.48)cm,体质量(65.70±7.99)kg,测试前均从未进行过专门的肌肉力量训练,优势上、下肢均为右侧。②实验方法:从站立开始加摆臂的反向蹲跳,要求受试者上体尽可能保持前后方向稳定,从站立位开始下蹲时上肢向下加速摆臂,并迅速向上蹬伸起跳。从站立开始不加摆臂的反向蹲跳,是排除上肢对蹲跳高度的影响。从半蹲开始加摆臂的无反向蹲跳,要求半蹲的角度控制在105°,静止状态下半蹲预备后,直接进入向上的蹬伸起跳过程,不能出现在起动瞬间身体重心先小幅下移再向上的情况。每种动作做3次,每次间隔10min。③实验评估:通过爱捷图像解析系统得出蹲跳高度,取成绩最好的一次采用Biodex Ⅱ型等速测力及康复系统检测受试者各关节肌力相对峰力矩。利用多因素优势分析法得出在慢速[60(°、快速[240(°)/s])/s]状态下,髋、膝、踝、肩、肘关节相对峰力矩与蹲跳高度的相关性。结果:①从站立开始加摆臂的反向蹲跳高度与各关节相对峰力矩的关系:在慢速状态时与髋关节伸肌相对峰力矩、踝关节背屈肌相对峰力矩、膝关节伸肌相对峰力矩呈明显相关(r=0.808,0.692,0.656),在快速状态时与肘关节屈肌相对峰力矩呈明显相关(r=0.770)。②从站立开始不加摆臂的反向蹲跳高度与各关节相对峰力矩的关系:在慢速状态时与踝关节背屈肌相对峰力矩呈明显相关(=0.747),在快速状态时与膝关节屈肌相对峰力矩呈明显相关(r=0.796)。③从半蹲开始加摆臂的无反向蹲跳高r度与各关节相对峰力矩的关系:从半蹲开始加摆臂的无反向蹲跳高度,在慢速状态时与髋关节伸肌相对峰力矩、踝关节背屈肌相对峰力矩、膝关节伸肌相对峰力矩呈明显相关(r=0.774,0.762,0.712),在快速状态时与肘关节屈肌相对峰力矩呈明显相关(r=0.843)。结论:①加摆臂的反向与无反向蹲跳,髋关节伸肌相对峰力矩、肘关节屈肌相对峰力矩分别是慢速、快速状态下影响其高度的首要因素。②不加摆臂的反向蹲跳,踝关节背屈肌相对峰力矩、髋关节伸肌相对峰力矩分别是慢速、快速状态下影响其高度的首要因素。③提示发展上肢肌肉力量对蹲跳高度的提高大有益处。     

新复合纤维蛋白胶可注射性磷酸钙人工骨的理学特性

目的:检测纤维蛋白胶复合β-磷酸三钙/磷酸二氢钙复合人工骨材料的物理学性能,评价纤维蛋白胶对β-磷酸三钙/磷酸二氢钙骨水泥性能的影响,以及其作为注射型复合人工骨用于修复骨缺损的可行性。方法:实验于2006-12/2007-06在南方医科大学珠江医院中心实验室和华南理工大学生物材料实验室完成。①材料:β-磷酸三钙由上海瑞邦生物材料有限公司提供,磷酸二氢钙为东泰化工赠,纤维蛋白胶购自广州倍绣生物技术有限公司。②复合材料制备:将β-磷酸三钙/磷酸二氢钙骨水泥按3∶1的比例充分混合后,与纤维蛋白胶按凝固后的体积2∶1体积比混合,制成复合人工骨材料。③观察指标:测定复合材料的凝固时间,抗压强度,抗稀散性能,并用扫描电镜观察其煅烧前后的显微结构特征,以未加纤维蛋白胶的磷酸钙水泥为对照(CPC组)。结果:复合人工骨材料的平均初凝时间长于CPC组(P<0.004),终凝时间在初凝时间后2～4 min;复合材料的抗压强度为(14.72±1.81)MPa。复合材料较CPC组有良好的抗稀散性能,扫描电镜发现,纤维蛋白胶贯穿于磷酸钙水泥晶体间,并将磷酸钙水泥晶体紧密连接。煅烧后复合材料的孔径有增大,空隙率为57.28%,并且微孔之间有空隙互相贯通。结论:该骨水泥复合材料凝固时间符合临床操作的需要;抗压强度达到松质骨强度的要求;煅烧后磷酸钙水泥的空隙率明显提高,有利于材料的降解。