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.     

Outcomes after neoadjuvant or adjuvant chemotherapy for cT2-4N0-1 non–small cell lung cancer: A propensity-matched analysis

Objective

Comparative survival between neoadjuvant chemotherapy and adjuvant chemotherapy for patients with cT2-4N0-1M0 non–small cell lung cancer has not been extensively studied.

Same-Day Yttrium-90 Radioembolization: Feasibility with Resin Microspheres

Purpose

To evaluate the feasibility of a same-day yttrium-90 (⁹⁰Y) radioembolization protocol with resin microspheres (including pretreatment angiography, lung shunt fraction [LSF] determination, and radioembolization) for the treatment of hepatocellular carcinoma (HCC) and liver metastases.

鼠李糖脂分批式发酵动力学模型

根据3.7 L瑞士Bioengineer KLF2000型发酵罐分批发酵的实验数据,利用GraphPad Prism软件对假单胞菌BS-03产鼠李糖脂生物表面活性剂的发酵动力学模型进行非线性拟合,说明Logistic模型和L-P模型能较好的描述假单胞菌BS-03发酵过程中的菌体生长、鼠李糖脂合成和限制性基质的消耗动力学。     

枯草杆菌Bacillus sp F26产过氧化氢酶的发酵条件

从内蒙古呼伦贝尔草原的盐碱湖中分离到的一株低度嗜盐嗜碱细菌Bacillus sp F26，能积累高水平过氧化氢酶（CAT）。对Bacillus sp F26发酵产过氧化氢酶的环境与营养条件的研究结果表明，其积累高水平过氧化氢酶的适宜环境条件为：温度37℃，种龄20-22h，接种量5％，装液量50mL／（250mL的摇瓶）。适宜发酵培养基组成（g／L）为：葡萄糖15，牛肉膏10，玉米浆10，酵母膏5，磷酸二氢钾1，氯化镁0．2，氯化钠50，碳酸钠10。采用上述条件进行摇瓶分批发酵实验，发酵20h，过氧化氢酶酶活达到16．32U／mL，细胞干重为4．12g／L。进一步研究发现，在对数生长后期（16h）添加2mmol／L的H2O2可以明显刺激产酶，在5L的发酵罐上进一步以指数速率方式流加H2O2，由于该流加方式可降低H2O2对细胞的毒害作用，过氧化氢酶酶活达到29．89U／mL，与分批发酵相比提高了92．8％。     

液膜法提取发酵液中的苯丙氨酸 Ⅱ.操作工艺条件

从芫花Ｄａｐｈｎｅ ｇｅｎｋｗａ条的乙酸乙酯可溶部分分到３个结果性化合物，借助于波谱分析手段推断出Ⅱ为西瑞香素，Ⅲ为ｄａｐｈｎｏｄｏｒｉｎ Ｂ。     

灵芪菌质发酵工艺初报

目的:探讨灵芪菌质发酵的工艺,验证药用真菌新型固体发酵的优越性.方法:将灵芝分别在普通基质、药性基质(含黄芪)、富硒药性基质中发酵,对三种基质中菌质的有效部位多糖的含量进行测定及动态研究,比较其变化.结果:三种基质中菌质有效部位多糖含量及其相对标准差分别为4.65%、1.61%,3.76%、1.99%,4.50%、1.86%;对灵芝和黄芪发酵组合的有效成分多糖、蛋白质及总皂苷进行动态变化研究,发现第28天是发生次生代谢最旺盛的时候,确定为发酵终点.结论:灵芝和黄芪发酵组合是可行的.     

耐酸性运动发酵单胞菌的筛选和酒精发酵条件的优化

通过酸性平板筛选,在作者所在实验室保藏的运动发酵单胞菌中,得到一株能在pH4.5时进行酒精发酵的菌株,其酒精产量为66.7g/L,与原菌株在pH6.5时的相同.通过单因素实验和正交实验,对该菌在酸性条件下的酒精发酵条件进行了优化.结果表明,在发酵温度为30～35℃,pH4.5,初糖质量浓度150g/L,酵母膏质量浓度4g/L,蛋白胨质量浓度为2g/L时,该菌的酒精产量达到最大,为71.7g/L.     

Low-dose lactulose produces a tonic contraction in the human colon

Lactulose (10-20 g day(-1)) is used to treat constipation. At this therapeutic dose, its effects on colonic motility remain unknown. Twenty-two healthy subjects swallowed a probe with an infusion catheter, six perfused catheters and a balloon connected to a barostat. Colonic phasic and tonic motor activity was recorded in fasting state. In group 1, four volunteers ingested 15 g lactulose and motility was recorded for 5 h after entry of lactulose into the caecum; in group 2, motility was recorded during (3 h) and 2 h after intracolonic infusion of isoosmotic and isovolumetric solutions containing sodium chloride alone (n = 9) or with 15 g lactulose (n = 9). In a last group of volunteers, isotopic colonic transit after ingestion of lactulose (10 g,n = 9) was assessed and compared with a control group (n = 17). Ingestion or intracolonic infusion of 15 g lactulose significantly decreased barostat bag volume (maximal decrease: 45 +/- 12% and 35 +/- 9% of basal value respectively). Phasic contractions remained unchanged. Tonic and phasic motility was unchanged by the isotonic and isovolumetric infusion of saline. Ingestion of lactulose significantly accelerated isotopic colonic transit time compared with the control group. We conclude that in healthy humans, 10-15 g ingestion or intracaecal infusion of lactulose produces a prolonged tonic contraction that may be involved in the laxative effect of lactulose.