Calibrated liposomal release of the anti-mitotic agent BI-2536 increases the targeting of mitotic tumor cells.

Cancer drugs which are specifically targeted at mitosis have generally under-delivered as a class. One likely reason is that only a small percentage of cancer cells in a tumor are actually dividing at any moment. If this is the case, then prolonged bioavailability in the tumor should significantly increase the efficacy of antimitotic agents. Here, we show that if the Plk1 inhibitor BI 2536 is co-encapsulated in a liposome with a pair of anions, its release rate is dependent on both the identity and stoichiometry of the anions. We created a library of liposomes with varying release rates using this approach and found that liposomal drug release rates correlated inversely with in vitro cancer cell killing. Xenografted mice treated with a single dose of slow-releasing liposomal BI 2536 experienced tumor volume decreases lasting 12 days and complete responses in 20% of mice. Treatment with two doses a week apart increased the response rate to 75%. This approach, which we termed Paired Anion Calibrated Release (PACeR), has the potential to revive the clinical utility of antimitotic cancer drugs which have failed clinical trials.

Resurgence of scarlet fever in China: a 13-year population-based surveillance study.

BACKGROUND: A re-emergence of scarlet fever has been noted in Hong Kong, South Korea, and England, UK, since 2008. China also had a sudden increase in the incidence of the disease in 2011. In this study, we aimed to assess the epidemiological changes before and after the upsurge. We also aimed to explore the reasons for the upsurge in disease in 2011, the epidemiological factors that contributed to it, and assess how these could be managed to prevent future epidemics. METHODS: In this observational study, we extracted the epidemiological data for all cases of scarlet fever between 2004 and 2016 in China from the Chinese Public Health Science Data Center, the official website of National Health Commission of the People's Republic of China, and the National Notifiable Infectious Disease Surveillance System. These data had been collected from 31 provinces and regions in China and included geographical, seasonal, and patient demographic information. We used descriptive statistical methods and joinpoint regression to examine the spatiotemporal patterns and annual percentage change in incidence of the upsurge of disease across China. FINDINGS: Between Jan 1, 2004, and Dec 31, 2016, 502 723 cases of scarlet fever, with ten fatalities, were reported in China, resulting in an annualised average incidence of 2·8807 per 100 000 people. The annual average incidence increased from 1·457 per 100 000 people in 2004 to 4·7638 per 100 000 people in 2011 (incidence rate ratio [IRR] 3·27, 95% CI 3·22-3·32; p<0·0001), peaking in 2015 (5·0092 per 100 000 people). The annual incidence after the 2011 upsurge of scarlet fever, between 2011 and 2016, was twice the average annual incidence reported between 2004 and 2010 (4·0125 vs 1·9105 per 100 000 people; IRR 2·07, 95% CI 2·06-2·09; p<0·0001). Most cases were distributed in the north, northeast, and northwest of the country. Semi-annual patterns were observed in May-June and November-December. The median age at onset of disease was 6 years, with the annual highest incidence observed in children aged 6 years (49·4675 per 100 000 people). The incidence among boys and men was 1·54 greater than that among girls and women before the upsurge, and 1·51 times greater after the upsurge (p<0·0001 for both). The median time from disease onset to reporting of the disease was shorter after the upsurge in disease than before (3 days vs 4 days; p=0·001). INTERPRETATION: To our knowledge, this is the largest epidemiological study of scarlet fever worldwide. The patterns of infection across the country were similar before and after the 2011 upsurge, but the incidence of disease was substantially higher after 2011. Prevention and control strategies being implemented in response to this threat include improving disease surveillance and emergency response systems. In particular, the school absenteeism and symptom monitoring and early-warning system will contribute to the early diagnosis and report of the scarlet fever. This approach will help combat scarlet fever and other childhood infectious diseases in China. FUNDING: National Key R&D Plan of China Science and key epidemiological disciplines of Zhejiang Provincial Health of China.

A model of cell-wall dynamics during sporulation in Bacillus subtilis.

To survive starvation, Bacillus subtilis forms durable spores. After asymmetric cell division, the septum grows around the forespore in a process called engulfment, but the mechanism of force generation is unknown. Here, we derived a novel biophysical model for the dynamics of cell-wall remodeling during engulfment based on a balancing of dissipative, active, and mechanical forces. By plotting phase diagrams, we predict that sporulation is promoted by a line tension from the attachment of the septum to the outer cell wall, as well as by an imbalance in turgor pressures in the mother-cell and forespore compartments. We also predict that significant mother-cell growth hinders engulfment. Hence, relatively simple physical principles may guide this complex biological process.

Role of CD56 in Normal Kidney Development and Wilms Tumorigenesis.

The cell-surface glycoprotein CD56 has three major isoforms that play important roles in cell adhesion and signaling, which may promote cell proliferation, differentiation, survival, or migration. It is an important molecule in normal kidney development and acts as a key marker in Wilms tumor stem and progenitor cells. Here, we review the structural and genetic features of the CD56 glycoprotein, and summarize its roles in the normal versus diseased metanephric blastema. We discuss areas of CD56-related research that may complement or improve existing Wilms tumor treatment strategies, including the antibody-drug conjugate lorvotuzumab mertansine that binds to CD56.