Investigation of Drug Delivery in Rats via Subcutaneous Injection: Case Study of Pharmacokinetic Modeling of Suspension Formulations

With the rising cost of drug research, “do more with less” has become a new emphasis in the pharmaceutical industry. Consequently, the early analysis of pharmacokinetic/pharmacodynamic, efficacy, and safety parameters for a new drug target is critical for ensuring informed decision-making as soon as possible during the drug discovery process. When absorption, distribution, metabolism, and excretion properties of compounds are suboptimal which is especially true during the early stages of drug discovery, obtaining the desired exposure can be challenging via the most common routes (oral, intravenous). Therefore, subcutaneous (SC) injection is often explored as an alternate route of delivery. Although SC injection is used widely in the industry, information about how to model and predict the absorption of drugs administered via SC injection is not readily available. In the current research, we analyzed the absorption behavior of 12 model compounds covering a wide range of physicochemical properties following SC injection. We introduced a compound-specific parameter, the absorption factor from single SC injections of suspension doses of each compound, to aid in modeling and predicting of drug absorption profiles. The pharmacokinetic models derived in this study are capable of describing and predicting the absorption properties of SC injection for individual compounds.     

NS-398对骨肉瘤细胞趋化功能的抑制作用及其机制研究

[目的]观察特异性环氧合酶抑制剂NS-398对骨肉瘤细胞株(MG-63)体外趋化和侵袭能力及VEGF-A表达的影响,以探讨特异性COX-2抑制剂对骨肉瘤体外转移能力的作用及机制.[方法]用趋化小室研究NS-398对肿瘤细胞趋化和侵袭能力的影响;用RT-PCR检测COX-2、VEGF-A在MG-63细胞的表达及NS-398对其的影响.[结果]NS-398可明显抑制MG-63细胞的趋化和侵袭能力,同时可降低VEGF-A的表达,但并不影响其COX-2的表达.[结论]COX-2抑制剂NS-398能抑制骨肉瘤细胞的转移,其机制与抑制肿瘤细胞的VEGF-A生成有关,有望成为抗肿瘤新药.     

PD98059对肝癌细胞Ras-MAPK信号转导的作用

目的:探讨PD98059对肝癌细胞信号转导的作用及其作用机制。方法:将PD98059加入肝癌细胞系SMMC-7721细胞中,通过细胞活力、DNA合成、MAPK活性和MAPK含量的变化,观察PD98059对肝癌细胞信号转导的作用。结果:PD98059可明显抑制SMMC-7721细胞活力、DNA合成、MAPK活性和MAPK含量(与对照组比较,P<0.05),其抑制作用具有浓度依赖性。结论:PD98059可通过阻断Ras-MAPK信号通路而发挥其抑制作用;Ras-MAPK通路极有可能成为肝癌治疗的新靶点。     

Morphine‐6‐glucuronide (M6G) for postoperative pain relief

Morphine‐6‐glucuronide (M6G) is morphine's active metabolite acting at the μ‐opioid receptor. Recent experimental human studies and 5 of 6 randomized clinical trials indicate that M6G causes adequate and long lasting pain relief comparable to morphine. There are various observations that M6G is associated with a reduction in the severity of side effects normally associated with opioid use, such as reduced postoperative nausea and vomiting (PONV) and reduced respiratory depression. The present drug profile provides a review of the pharmacological properties of M6G, the clinical evidence relating to its efficacy and safety, and discusses its future role in the treatment of postoperative pain.     

黄芪甲苷对肺纤维化大鼠的治疗作用及对肺组织中血清和糖皮质激素调节蛋白激酶1表达的影响

【目的】研究黄芪甲苷对肺纤维化（PF ）大鼠的治疗作用及对肺组织中血清和糖皮质激素调节蛋白激酶1（SGK1）表达的影响。【方法】36只SD大鼠,随机分为对照组、模型组和黄芪甲苷干预组。模型组和干预组气管内注射博来霉素（BLM ,5 mg／kg）诱导PF ,对照组在相同条件下给予生理盐水。干预组大鼠d2开始每天经胃管灌服0．1 g／L黄芪甲苷2 m L ,其余两组相同条件下给予生理盐水。治疗的d7和d28处死动物取出肺组织,进行病理学观察;用免疫组化和RT‐PCR检测各组鼠肺组织SGK1蛋白及mRNA表达的水平。【结果】病理学观察显示：与模型组比较,干预组肺泡炎和纤维化程度均减轻,SGK1蛋白及mRNA表达显著降低;与对照组比较,干预组存在一定程度肺泡炎和纤维化,SGK1蛋白及mRNA表达明显高于对照组。【结论】黄芪甲苷可能通过抑制SGK1的过度表达,对实验性大鼠PF具有良好的治疗作用。     

Present and Emerging Biomarkers in Immunotherapy for Metastatic Non-Small Cell Lung Cancer: A Review

Targeting the immune system, especially the PDL-1/PD-1 axis, has significantly improved the outcomes of metastatic lung cancer patients. However, only a portion of patients will benefit significantly from PD(L)1 therapeutics alone or in combination with either chemotherapy or anti-CTLA4 antibody. It is therefore important to study predictive biomarkers to help select the patients who will experience the most benefit from immunotherapy. In this paper, the current status of PDL-1 expression on tumour cells, the smoking status of patients, tumour mutational burden, gut microbiome and STK11 and KEAP1 mutations in the tumour as predictive biomarkers for PD(L)-1-based immunotherapy are summarized.