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.

固体硅胶隆鼻术后感染排异的原因与预防探讨

感染及排异是固体硅胶隆鼻术较为严重的并发症。其发生原因主要在于手术适应证掌握不当；硅胶假体的质量不过关，假体的修雕成形不佳，假体消毒处理不严；手术操作及术后处理欠妥等。提出了加强术前体检及适应证的掌握，选择质量过关的硅胶假体，努力提高术者的审美及专业技术水平，设计修雕成形出恰当的假体，并注意规范假体的消毒处理，这都可有效减少感染及排异并发症的发生。强调手术操作时尽量减少局部组织的损伤，勿剥破鼻部的皮肤及粘膜，并做好术后的处理及护理，这同样也是减少感染排异并发症的关键。     

废弃物处理——一个刻不容缓的问题

介绍了香港环保署通过１０年努力的完整的固体废弃物收运，处理及处置系统，以及他们为实现废弃物减量化和资源化所采取的策略与行动。由此提出上海浦东新区在固体废弃物管理和环卫设施建设上应加强关注；逐步按规划实施；采用多种形式设计，建造，营运环卫设施以及开展全方位宣传教育活动的建议。     

Solid and Cystic Tumor of the Pancreas in an Adult Male

A solid and cystic tumor (SCT) was located at the head of the pancreas in a 43-year-old Japanese male, and pancreatoduodenectomy was performed on the suspicion of papillary carcinoma or cystadenocarcinoma of the pancreas. The lesion, which measured 4.5 X 4.5 X 4.0 cm, was clearly demarcated by connective tissue. The cut surface showed solid grayish-white areas with central cystic degenerative changes. The solid areas consisted of small round cells proliferating in a small solid or a pseudopapillary pattern. The tumor cells partially invaded the surrounding normal pancreatic parenchyma. Immunohistochemical studies revealed positive staining for alpha-1-antitrypsin and neuron-specific enolase, but no staining for known pancreatic hormones. Moreover, ultrastructural studies showed the absence of zymogen granules and the presence of anullate lamellae and neurosecretory granules. On the basis of these findings, a diagnosis of SCT of the pancreas was established. In order to clarify the histogenesis and biological behavior of the tumor, it is necessary to accumulate and analyze similar cases, an endeavor which in turn will contribute to the successful management of this disease. Acta Pathol Jpn 41: 763-770, 1991.     

Ultrastructural features of solid/trabecular areas in differentiated thyroid carcinoma

The presence of areas exhibiting a solid/trabecular pattern of growth within an otherwise differentiated thyroid carcinoma represents a source of controversy as regards its proper classification and biologic and prognostic significance. The aim of the current study was to investigate the ultrastructural features of solid/trabecular areas in differentiated thyroid carcinoma and to compare those features with the submicroscopic profile of differentiated, poorly differentiated (insular), and undifferentiated (anaplastic) variants of thyroid cancer. The study series included differentiated carcinoma with solid/trabecular areas (3 cases), conventional papillary carcinoma (4 cases), follicular variant of papillary carcinoma (4 cases), poorly differentiated (insular) carcinoma (3 cases), and undifferentiated (anaplastic) carcinoma (3 cases). It was found that the solid/trabecular areas in differentiated carcinoma and poorly differentiated (insular) carcinoma share similar ultrastructural features and overall retain, even if attenuated, many of the submicroscopic attributes of differentiated carcinomas. In particular, nests of neoplastic cells were observed showing a highly developed cytosecretory apparatus and the presence of numerous abortive/rudimentary follicles, and intercellular and intracellular (intracytoplasmic) lumina/canaliculi of variable morphology. The study supports the hypothesis that the solid/trabecular areas do not merely represent an architectural pattern but rather should be regarded as the expression of a process of reduced differentiation similar to that of poorly differentiated (insular) carcinoma.     

新鲜组织块标本经乙醇直接固定二年的流式细胞术DNA分析

本文报道了一种实体组织用于DesoxyribonucleicAcid(DNA)分析的Flowcy tometry(FCM) )样品保存新方法 ,即新鲜组织块乙醇直接固定法。所用样品为头颈部肿瘤手术切除的新鲜标本 3 0例 ,每例标本重约 0 5～ 1 g ,均等分为两份 ,1份置 70 %乙醇直接固定 ,室温放置 ,待两年后FCM检测。另一份置生理盐水中立即行流式细胞术DNA分析。两组样品经机械法制成单细胞悬液 ,PI染色后上机检测。结果显示 :从两组样品的DNA直方图分析 ,CV(coefficiencyofvariation)值、GO/G1、S及G2 /M各期比率无显著差异 (P >0 0 5)。我们认为在样品收集短期内难以完成 ,需积累保存 ,或需保存半年以上者 ,且不具备低温冷冻设备的条件下 ,新鲜组织块乙醇直接固定法是优于将组织块先制备成单细胞悬液再行乙醇固定的流式细胞术DNA样品保存方法     

实体肿瘤药物输运与给药方式的集中参数模型及实验研究

目的研究不同给药方式对实体肿瘤抗癌药物疗效的影响,并通过动物实验验证。方法分别建立体内药代动力学和肿瘤内药物输运的集中参数模型,模拟单次快速注射和等时间间隔三次快速注射时肿瘤间质组织药物浓度Ct随时间的变化。实验小鼠分为两组,分别进行抗癌药羟基喜树碱(HCPT)单次快速注射和等时间间隔3次快速注射,观察其肿瘤内药物平均浓度。对数值模拟结果和动物实验结果进行比较。结果数值模拟结果显示,对于相同总量药物,等量等间隔的三次给药,肿瘤间质组织药物浓度Ct高于单次给药。动物实验的实测结果相同。结论3次给药的效果显著优于单次给药。集中参数模型基本能够定量反映不同给药方式的效果。