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.     

基于非标准协议无线通信的个人健康监护系统设计

基于非标准协议的短距离无线通信，具有成本低、易开发、低功耗的优点，非常适用于小范围内的数据传输。提出一种基于非标准无线通信芯片nRF24L01的个人健康监护系统设计方案，并将其与现有的、基于标准协议无线通信的个人健康监护系统进行比较。结果表明：基于非标准协议无线通信的个人健康监护系统具有效率高、功耗低、通信性能好的特点。     

Evaluation of the impedance tonometers TGDc-01 and iCare according to the international ocular tonometer standards ISO 8612

BACKGROUND: Two new tonometers have been introduced that are based on the impedance principle. Both the TGDc-01 (transpalpebral measurement) and the iCare (corneal measurement) do not require corneal anaesthesia. The present work presents an evaluation of both devices. METHODS: Comparative measurements using one of the new tonometers and applanation tonometry were performed by one investigator according to the international standard for ocular tonometer (ISO 8612). Measurements were performed on 445 eyes without corneal pathology from 243 patients. Six measurements were performed for iCare and 3 for TGDc, immediately followed by 3 applanation tonometry measurements. RESULTS: The correlation coefficient with respect to applanation tonometry was 0.81 for TGDc and 0.95 for iCare. TGDc-01 measurements showed an average deviation of 3.1 +/- 2.6 mmHg to those of Perkins applanation tonometry. The maximum difference was 28.7 mmHg below and 9.8 mmHg above the results of applanation tonometry. iCare showed an average deviation of 2.5 +/- 1.1 mmHg to Goldmann tonometry. The maximum difference was 14.5 mmHg below and 9.8 mmHg above. CONCLUSIONS: The results of both new tonometers showed a good correlation with the reference applanation tonometric methods, but the strict requirements of ISO 8612 are not fulfilled by either tonometer at present. Additionally, transpalpebral measurements with the TGDc-01 showed unacceptably high variability.     

Prospect for enzyme therapy in glycogenosis II variants: a study on cultured muscle cells

Summary Impairment of skeletal muscle function is the common feature of distinct clinical forms of glycogenosis type II. In the present study, muscle cultures from different patients were used to investigate the cause of clinical heterogeneity and the feasibility of enzyme replacement therapy. The activity of acid -glucosidase appears to be the primary factor in determining the extent of lysosomal glycogen storage in muscle, and thereby the clinical severity of the disease. Neutral -glucosidases do not seem influencial. Correction of the enzymatic defect was achieved in skeletal muscle cultures from patients by administration of a high-uptake form of acid -glucosidase, purified from human urine. The enzyme reaches the lysosomes, including the glycogen storage vacuoles, and the lysosomal glycogen content is reduced to control level. In normal muscle cells 20% of the total cellular glycogen pool is segregated in lysosomal compartments. This percentage is higher than in fibroblasts, which may partly explain why muscles are more prone to store glycogen. The relevance of this study for enzyme therapy is discussed.     

Glucose preferences in wild and domestic guinea pigs

Male wild (Cavia aperea) and domestic (C. porcellus) guinea pigs were tested in two-bottle choice tests for preferences between glucose solutions of different concentrations and de-ionized water. Wild males showed significant preferences for concentrations between 0.025 and 0.4 M glucose while domestic males preferred only the 0.2 M glucose solution to de-ionized water. C. aperea males also consumed significantly greater volumes of liquid per kg body $\text{wt.}{}^{\mathrm{<mtext>3</mtext><mtext>4</mtext>}}$ during the glucose tests than did the C. porcellus males. These comparative results contrast sharply with those obtained by other authors with wild and domestic Norway rats.     

A nucleotide insertion in exon 4 is responsible for the absence of expression of an HLA-A*01 allele

HLA class I typing performed in parallel by molecular biology and serology has revealed cases where an HLA class I allele was identified whereas the corresponding antigen was not detected on the cell surface. In the present report, we describe four members of a family in whom an HLA-A 1 allele identified at the molecular level was typed as A "blank" by lymphocytotoxicity. This serologically blank antigen was undetectable by isoelectric focusing (IEF). Sequencing of the HLA-A*01 allele from the promoter region to the eighth exonic region revealed insertion of a "C" nucleotide at the beginning of the fourth exon as compared to the common HLA-A*0101 allele. This mutation causes a frame shift, giving rise to an early stop codon in the fourth exon.     

The effects of nifedipine on platelet aggregation and plasma 6-keto-PGF1α, and its interaction with indomethacin

Summary Pre-incubation of human platelets with nifedipine in vitro or treatment of normal volunteers with nifedipine, 30 mg daily for one week, did not alter ADP induced aggregation measured by whole blood aggregometry. 6-oxo-Prostaglandin F₁ remained undetectable in plasma following oral administration of nifedipine to normal volunteers. The hypotensive response to intravenous nifedipine administration was similar in spontaneously hypertensive rats pretreated with indomethacin or placebo. These results conflict with previous reports that nifedipine alters platelet aggregation and prostaglandin metabolism.     

HIV-1 CRF55_01B毒株流行特征的研究进展

CRF55_01B是我国报道的HIV-1主要流行毒株之一,具有较为独特的流行病学和基因进化特征。近几年HIV-1分子流行病学监测发现CRF55_01B已经成为我国第五个主要流行HIV-1毒株。本研究从他的发现起源、流行情况、致病性和耐药性及参与的重组等方面进行综述,并讨论了与其流行密切相关的社会和生物学因素。     

滕州市致病性弧菌检测报告

报道了1995年以来,滕州市致病性弧菌种类、分,布等病原学检测情况。共检疑似霍乱病人粪便1562人份,检出致病性弧菌127株,检出率为8．13％,其中非01群霍乱弧菌居首位83株占65．35％,其次为麦氏弧菌13株占10．4％,溶藻弧菌11株,河弧菌9株,副溶血弧菌6株,弗尼期弧菌5株。83株非01群霍乱弧菌可分型占61株,分布8个血清型,定型率为73．49％,127株致病性弧菌产类霍乱肠毒素（G）47株占37．00％,以非01群霍乱弧菌产生类CT所占比例为最高,从而说明它在毒力和致病性方面占有重要地位。