The absorption enhancement of norisoboldine in the duodenum of adjuvant‐induced arthritis rats involves the impairment of P‐glycoprotein

Lindera aggregata (Sims) Kosterm root has been used in traditional Chinese medicine for the treatment of rheumatism palsy, dyspepsia and frequent urination for a long time. Norisoboldine, the main active constituent of this herb drug, possesses outstanding anti‐arthritis activity. However, the in vivo disposition of norisoboldine is known to a limited extent, especially under the pathological condition of rheumatoid arthritis (RA). The aim of this study is to investigate whether and how the absorption of norisoboldine is altered in adjuvant‐induced arthritis (AIA) rats. Comparative studies of the intestinal absorption of norisoboldine in normal and AIA rats at different pathological stages of the arthritis were performed using in situ single‐pass intestinal perfusion, and the effects of an inhibitor of efflux proteins were also investigated. Norisoboldine was shown to be a substrate of P‐glycoprotein (P‐gp), as P‐gp inhibitor verapamil markedly increased the permeability coefficient (P _eff) of norisoboldine by 88% in the intestine of normal rats. Compared with normal rats, AIA rats displayed increased P _eff values of norisoboldine by 84% and 86% on day 5 and day 10 after the appearance of the secondary response of arthritis, respectively. Verapamil could eliminate the difference of intestinal absorption of norisoboldine between normal and AIA rats. Further studies showed that impaired expression and activity of P‐gp in AIA rats play a decisive role in the absorption enhancement of norisoboldine. Notably, the impairment of P‐gp function positively correlated with the severity of arthritis. Copyright © 2016 John Wiley & Sons, Ltd.     

Controversies in the management of stage IIIA non-small-cell lung cancer

New developments in the management of non-small-cell lung cancer, as well as recent proposals for changing the current lung cancer staging system, are posing a challenge in the therapeutic decision making regarding this disease. For the last two decades, the management of stage IIIA (N2) disease has been controversial and the target for clinical trials has been to determine the best therapeutic approach that may result in better survival outcomes without increasing toxicity. For many years, combined modality treatment (systemic chemotherapy plus radiation therapy) became the standard of care in this setting. However, the poor outcomes seen with combined modality for N2 has obligated us to explore other possibilities. In this sense, recent clinical trials in the neoadjuvant setting using chemotherapy alone or combined modality are providing fruitful results and shifting the paradigm on this stage. A recent, large randomized multicenter trial argues against what has slowly become a current practice in some centers – the use of preoperative modality for N2 disease. Another controversy that we will discuss here is the acceptance of adjuvant therapy for resected stage IB–IIIA non-small-cell lung cancer. It was not long ago that adjuvant radiation therapy was still the standard of care for patients who have pathological nodal disease. We will present the current data on these debatable issues and how to implement this new knowledge into clinical practice.     

Multidisciplinary management of resectable adenocarcinoma of the pancreatic head

Although surgery is considered the only treatment to offer patients with localized pancreatic adenocarcinoma a chance of cure, resection alone is rarely sufficient for long-term survival. High rates of postoperative recurrence and subsequent disease-related mortality have, over the past two decades, encouraged the study and use of multimodality strategies that include adjuvant systemic chemotherapy and radiation. These modalities have been utilized both preoperatively and postoperatively with encouraging results. Moreover, their use has led increasingly to the development of institutional multidisciplinary groups with a focused interest in the care of patients with pancreatic malignancy, which have become responsible for the diagnosis, staging, treatment, follow-up and study of these patients. We review the rationale for the use of and the outcomes that may be achieved through the use of a multidisciplinary approach to patients with resectable adenocarcinoma of the pancreatic head.     

Vaxfectin: a versatile adjuvant for plasmid DNA- and protein-based vaccines

Importance of the field: Many vaccines require the use of an adjuvant to achieve immunity. So far, few adjuvants have advanced successfully through clinical trials to become part of licensed vaccines. Vaxfectin (Vical, CA, USA) represents a next-generation adjuvant with promise as a platform technology, showing utility with both plasmid DNA (pDNA) and protein-based vaccines.

Areas covered in this review: This review describes the chemical, physical, preclinical and clinical development of Vaxfectin for pDNA-based vaccines. Also included is the preclinical development of Vaxfectin-adjuvanted protein- and peptide-based vaccines.

What the reader will gain: The reader will gain knowledge of vaccine adjuvant development from bench to bedside.

Take home message: Vaxfectin has effectively boosted the immune response against a range of pDNA-expressed pathogenic antigens in preclinical models extending from rodents to non-human primates. In the clinic, Vaxfectin-adjuvanted pDNA-based H5N1 influenza vaccines have been shown to be well tolerated and to result in durable immune responses within the predicted protective range reported for protein-based vaccines.     

小鼠精子Sp17与IL-5融合蛋白的免疫性避孕效应和安全性研究

目的:研究小鼠精子抗原Sp17与佐剂IL-5融合蛋白避孕疫苗的避孕效应及毒性作用。方法:重组蛋白疫苗Sp17-IL-5经鼻内免疫途径免疫小鼠后,观察其妊娠率、每胎产仔数,对免疫后小鼠的重要脏器进行病理学检查,并对免疫后小鼠及其子代的骨髓有核红细胞的微核及精子进行检测。结果:蛋白疫苗Sp17-IL-5鼻内免疫雌性Balb/c小鼠可明显降低受孕率和每胎产仔数,免疫后小鼠的重要脏器病理学检查未见明显异常改变,免疫后小鼠及其子代的骨髓有核红细胞微核率及精子畸形率均无明显变化。结论:重组蛋白疫苗Sp17-IL-5有较明确的抗生育作用,对免疫后小鼠及其子代未产生明显的毒副作用。     

Effect of genetic adjuvants on immune respondance,growth and hormone levels in somatostatin DNA vaccination-induced Hu lambs

The aim of current study was to evaluate the prospects of adjuvants against DNA vaccination (pES/2SS) encoding somatostatin (SS) and hepatitis B surface antigen fusion gene. A total of 60 female Hu lambs were divided into 6 groups and vaccinated in the context of various adjuvants (and controls): pE-CpG, Escherichia coli DH5α DNA, crude liposomes or GM-CSF in combination with the pES/2SS plasmid. Controls included pES/2SS only vaccinated and physiological saline groups. The antibody against SS level in the E. coli DH5α DNA group was significantly increased compared to that in the pES/2SS vaccine alone. Vaccination with pES/2SS/pE-CpG or pES/2SS/E. coli DH5α resulted in elevated weight gains that were 33.0 and 31.6% higher, respectively, than in saline group and pES/2SS only vaccinated controls. The concentrations of GH and IGF-I in the DNA vaccine groups were remarkably higher than those in the saline group, and those with positive antibody higher than negative antibody. These results suggested that different adjuvant/pES/2SS combinations can enhance the immune effect and had significant positive effects on growth.     

Adjuvant chemotherapy for bladder cancer

Radical cystectomy is a standard treatment for patients with muscle-invasive bladder cancer. The presence of occult micrometastatic disease is responsible for both local and distant failure after radical surgery. Postoperative administration of chemotherapy in bladder cancer patients can theoretically give the same survival advantage demonstrated in patients with breast and colon cancer. Studies evaluating adjuvant chemotherapy in patients with pT3–pT4 and/or pN+ M0 disease have major deficiencies in terms of sample sizes, early stopping of patient entry, statistical analyses, reporting of results and drawing conclusions. A recent meta-analysis including all previously published randomized trials concludes that, currently, there is insufficient evidence to reliably recommend adjuvant chemotherapy. The results of appropriately sized randomized trials are needed before any definitive conclusions can be drawn.     

肿瘤患者的生育风险评估

晚婚晚育的趋势、癌症患者的低龄化、生存率和生存时间的改善让越来越多的患者和医务工作者关注如何在治疗癌症过程中保护患者的生育能力。从造成生育风险的因素、妊娠对癌症患者的影响及伦理学方面简要叙述肿瘤患者的生育风险评估方法。