Phase I Dose-Escalation Study of SCB01A,a Microtubule Inhibitor with Vascular Disrupting Activity,in Patients with Advanced Solid Tumors

Lessons Learned

• SCB01A is a novel microtubule inhibitor with vascular disrupting activity.
• This first‐in‐human study demonstrated SCB01A safety, pharmacokinetics, and preliminary antitumor activity.
• SCB01A is safe and well tolerated in patients with advanced solid malignancies with manageable neurotoxicity.

BackgroundSCB01A, a novel microtubule inhibitor, has vascular disrupting activity.MethodsIn this phase I dose‐escalation and extension study, patients with advanced solid tumors were administered intravenous SCB01A infusions for 3 hours once every 21 days. Rapid titration and a 3 + 3 design escalated the dose from 2 mg/m² to the maximum tolerated dose (MTD) based on dose‐limiting toxicity (DLT). SCB01A‐induced cellular neurotoxicity was evaluated in dorsal root ganglion cells. The primary endpoint was MTD. Safety, pharmacokinetics (PK), and tumor response were secondary endpoints.ResultsTreatment‐related adverse events included anemia, nausea, vomiting, fatigue, fever, and peripheral sensorimotor neuropathy. DLTs included grade 4 elevated creatine phosphokinase (CPK) in the 4 mg/m² cohort; grade 3 gastric hemorrhage in the 6.5 mg/m² cohort; grade 2 thromboembolic event in the 24 mg/m² cohort; and grade 3 peripheral sensorimotor neuropathy, grade 3 elevated aspartate aminotransferase, and grade 3 hypertension in the 32 mg/m² cohort. The MTD was 24 mg/m², and average half‐life was ~2.5 hours. The area under the curve‐dose response relationship was linear. Nineteen subjects were stable after two cycles. The longest treatment lasted 24 cycles. SCB01A‐induced neurotoxicity was reversible in vitro.ConclusionThe MTD of SCB01A was 24 mg/m² every 21 days; it is safe and tolerable in patients with solid tumors.     

3种霍乱弧菌检测方法在外环境标本中的应用研究

目的：通过改进霍乱弧菌检测的技术手段，提高外环境标本中霍乱弧菌的检出率。方法：将常规分离鉴定法、PCR检测法和胶体金免疫层析试验法同时用于检测霍乱流行期间的外环境标本，并对其现场应用结果进行比较分析。结果：3种方法检测80份外环境标本霍乱弧菌的结果显示：它们均未出现假阳性，3种方法各有优势，且结果相互符合性好，但也存在各自弱点。结论：只用单一种方法来检测外环境标本霍乱弧菌存在明显不足。建议在外环境霍乱监测中选用胶体金法进行初筛，再用常规法和PCR法检测。最大限度减少漏检的可能性。     

18F-FDG PET can replace conventional work-up in primary M staging of nonkeratinizing nasopharyngeal carcinoma.

Conventional work-up (CWU) with chest radiography, abdominal ultrasonography, and skeletal scintigraphy has limited value in M staging of nonkeratinizing nasopharyngeal carcinoma (NPC). Our aim was to evaluate whether (18)F-FDG PET could replace CWU by comparing their diagnostic efficacies. METHODS: Patients with histologically proven nonkeratinizing NPC and no prior treatment were prospectively enrolled. All study participants underwent CWU and (18)F-FDG PET for primary M staging. Distant metastasis was considered to be present if there was any reliable evidence identified within 1 y after diagnosis. The comparative diagnostic efficacies of (18)F-FDG PET, CWU, and the combination of (18)F-FDG PET and CWU (PET+CWU) were evaluated using the areas under the receiver-operating-characteristic (ROC) curves. RESULTS: Sixty-one (20.3%) of 300 eligible patients were found to have distant metastases. On a patient-based analysis, (18)F-FDG PET was found to be more effective than CWU (P < 0.001), whereas it was equally effective with PET+CWU (P = 0.130). On region-based analyses, (18)F-FDG PET was more effective than skeletal scintigraphy and chest radiography for detecting bone metastases (P < 0.001) and chest metastases (P < 0.001), respectively. (18)F-FDG PET and abdominal ultrasound were equally effective for detecting hepatic metastases (P = 0.127). On region-based analyses, the combination of (18)F-FDG PET and CWU did not yield any noticeable increase in diagnostic efficacy. CONCLUSION: (18)F-FDG PET can replace CWU in primary M staging of nonkeratinizing NPC.     

磁性远红外寝具对高脂血症患者血脂、血糖及抗氧化作用的影响

目的 观察磁性远红外寝具对高脂血症患者血脂、血糖及抗氧化作用的影响。方法 60例高脂血症患者，按随机数字表法分为实验组（30例）和对照组（30例）。实验组每晚（6～8h）均使用磁性远红外寝具，连续2个月。对照组用普通寝具。两组均于实验前后取全血，测定血脂、血糖及抗氧化指标等。结果 实验组实验后血清总胆固醇，甘油三酯含量明显低于实验前；实验前后血清高密度脂蛋白胆固醇（HDL-ch）含量及血糖无明显变化（P〉0．05）。实验组实验后MDA含量较实验前显著下降（P〈0．05），而血清超氧化物歧化酶（SOD）活性较实验前显著提高（P〈0．01）；实验前后血清中NO含量无明显变化（P〉0．05）。对照组实验前后以上各项指标较实验前均无明显变化，差异均无显著性（P〉0．05）。结论 磁性远红外寝具对高脂血症患者具有降血脂作用及抗氧化作用。     

2型糖尿病患者血浆TNF-α水平与胰岛素抵抗的关系

目的　探讨 2型糖尿病患者血浆TNF -α水平与胰岛素抵抗的关系。方法　用放免法测定 3 8例非肥胖型 2型糖尿病患者及 3 0例正常人的血浆TNF -α浓度 ,计算胰岛素敏感指数 (ISI)和体重指数 (BMI) ,并将血浆TNF -α分别与ISI、BMI做直线相关分析。结果　 2型糖尿病患者血浆TNF -α水平为 3 0 79± 6 64fmol/ml,显著高于正常对照组 ,(P <0 0 0 5 ) ;糖尿病组ISI为 -5 64±0 3 5 ,而正常对照组为 -4 0 4± 0 43 ,二者有显著性差异 (P <0 0 0 1。 2型糖尿病患者血浆TNF -α水平与ISI的相关系数为 -0 67(P <0 0 0 5 ) ,呈显著负相关 ;在女性患者 ,血浆TNF -α水平与BMI呈显著正相关 ,直线回归方程为Y =1 2 19X +2 40 6,r =0 68(P<0 0 0 5 )。结论　非肥胖型 2型糖尿病患者存在胰岛素抵抗 ;非肥胖型 2型糖尿病患者血浆TNF -α水平升高 ,并可间接反映胰岛素抵抗程度