Status quo of current clinical drug regimens for small cell lung cancer and new progress in the potential target drug therapeutic regimens / 中国药房

Small cell lung cancer （SCLC） accounts for about 15% in lung cancer and is highly malignant， heterogeneous and invasive. Etoposide combined with platinum-based chemotherapy is the basis of standard first-line treatment for extensive-stage SCLC， but suffers from the problem of susceptibility to drug resistance and relapse. In recent years， the emergence of new immunological drugs and novel cytotoxic drugs has improved the survival of SCLC patients to a certain extent， especially bringing therapeutic hope to patients with relapsed/refractory SCLC. In this paper， we review the current clinical drug regimens and the new progress of potential target drug therapeutic regimens for the treatment of SCLC. At present， the first-， second- and third-line schemes of SCLC include etoposide+carboplatin， atezolizumab+etoposide+platinum， adebrelimab， topotecan， docetaxel， etc.； the current drug targets for the treatment of SCLC mainly focus on topoisomerase Ⅱ/Ⅰ， DNA， the immune checkpoint molecules programmed death-1/programmed death-ligand 1， tubulin， etc. The potential target drug therapeutic options include alisertib+ paclitaxel， rovalpituzumab， APG-1252， etc.， and mainly focus on DNA damage response pathways and immune pathways， which can achieve the prolongation of patient survival by exerting anti-tumor effects through aurora kinase A and other potential targets.

Nanobubbles: A Novel Targeted Drug Delivery System

Abstract Nanobubbles are nanometer size bubbles having different constituents of varying physicochemical characteristic for the inner core and outer shell. Nanobubbles are mainly fabricated to improve the stability, bioavailability and improve the biodistribution of the delivered drug to the specific targeted site. Their small sizes bubbles allow the possibility of extravasation from blood vessels into the surrounding tissues and ultrasound-targeted site-specific release with minimal invasiveness. Nanobubbles are developing as important contrast agents for imaging and carriers for drug delivery at targeted region. Sonication is the primary method for preparation of nanobubbles followed by thin-layer evaporation, high shear emulsification, mechanical agitation and coacervation or coalescence. With exposure to ultrasound/extracorporeal shock waves, the drug is liberated from the nanobubbles into the target cells. This review paper is an effort to reveal the different formulation development techniques briefly and varying shell and core content for developing nanobubbles.

Human Annexin A5: from Biomarkers to Therapeutic Candidates / 中国生物化学与分子生物学报

Human annexin A5 (hAnxA5) as an important functional protein molecule in the human body, widely exists in human cells and body fluids. hAnxA5, a member of annexin group with complex structure, exhibits a variety of biological functions by reversibly and specifically binding phosphatidylserine (PS) in a calciumdependent manner and plays an important role in many human physiological processes. This paper has made induction and summary of the biochemical characteristics, mechanism, biological effects and important biomedical applications of hAnxA5. The hAnxA5 is present in the form of monomer and often exercise biological functions in a polymer. hAnxA5 affects the occurrence and development of pathological phenomena, such as vascular thrombosis disease, autoimmune disease, tumor disease, pulmonary fibrosis and lung injury, nonalcoholic fatty hepatitis, etc. As a biomarker, hAnxA5 has also been adopted in the study of diseases such as tumor, neurodegenerative diseases, heart failure, acute renal injury, asthma and so on. As novel drug candidates, hAnxA5 and its derivatives have been designed and applied to the therapeutic exploration of many kinds of diseases, especially for thrombotic diseases. There are also some gaps and shortcomings for hAnxA5 research. The in-depth of its research will not only expand the understanding of structure and functional relationships, but also promote its application in the field of biomedicine.

The effects of HBx on the proliferation and invasion of hepatocellular carcinoma and sorafenib resistance / 中华肝胆外科杂志

Objective:To investigate the effects of hepatitis B virus X (HBx) on hepatocellular carcinoma (HCC) proliferation, invasion, and sorafenib resistance.Methods:HepG2 cell line infected with HBx ORF lentivirus was set as the HBx high expression group and infected with empty vector was set as the negative control group. The interference group was infected with the HBx siRNA virus based on the HBx high expression group to reduce HBx expression. Interference control group as interference group but with infected empty vector virus. Western blotting was used to measure the protein level of HBx. Cell proliferation, invasion ability, and sorafenib semi-inhibitory concentration (IC50) of HCC cells under different HBx expression levels were respectively detected by cell proliferation assay kit, Transwell invasion assay, and cell titer-glo kit.Results:Western blotting showed that the stable cell lines were successfully established. Cell proliferation of the HBx high expression group was better than that of the blank control and negative control groups, and the cell proliferation of the interference group was lower than that of the interference control and HBx high expression groups, and the differences were all statistically significant ( P<0.05). The number of cells crossing Matrigel gel was (46.2±4.1), (50.7±5.1) and (48.2±5.2) in the blank control group, negative control group, and interference group, respectively. The number of cells crossing Matrigel gel in the HBx high expression group (124.2±8.3) and the interference control group (117.2±7.5) were higher than the above three groups, respectively, and the differences were all statistically significant ( P<0.05). The IC50 of cells in the HBx high expression group and the interference control group were (5.36±0.31) μmol/L and (5.48±0.20) μmol/L, respectively, which were higher than those in the blank control group, the negative control group, and the interference group (4.75±0.22) μmol/L, (4.60±0.14) μmol/L and (3.98±0.03) μmol/L. The differences were all statistically significant ( P<0.05). Conclusion:HBx promoted the tumor proliferation and invasion of HepG2 HCC cells, enhanced the ability to sorafenib resistance, and inhibited apoptosis.

Precise nano-targeted technology based on disease microenvironment targeting / 医学研究生学报

Research into the rational delivery and targeting of pharmaceutical, therapeutic, and diagnostic agents is at the forefront of projects in nanomedicine with the launch of ‘precision medicine’, and into the era of ‘precise’ targeted nano drug delivery system design. According to the lesion feature of disease endangering human health, it is one of the important strategies to design nano drug delivery system that targets each of the lesions which could change the distribution of drugs in the body, specifically increasing the concentration of drugs in the target sites and reducing the concentration of non-target sites, so as to enhance the efficacy, reduce adverse reactions and achieve precise nano-targeted treatment of diseases.at last. This article introduces the design principle and latest research progress of drug passive and active nano targeting delivery of drugs based on local microenvironment characteristics of lesions in tumors, atherosclerosis, inflammatory diseases in recent years, aiming to provide reference and basis for the design of more nano-targeted drug delivery systems for tumors and other diseases.

Application of network biology on study of traditional Chinese medicine / 中国中药杂志

With the completion of the human genome project, people have gradually recognized that the functions of the biological system are fulfilled through network-type interaction between genes, proteins and small molecules, while complex diseases are caused by the imbalance of biological processes due to a number of gene expression disorders. These have contributed to the rise of the concept of the "multi-target" drug discovery. Treatment and diagnosis of traditional Chinese medicine are based on holism and syndrome differentiation. At the molecular level, traditional Chinese medicine is characterized by multi-component and multi-target prescriptions, which is expected to provide a reference for the development of multi-target drugs. This paper reviews the application of network biology in traditional Chinese medicine in six aspects, in expectation to provide a reference to the modernized study of traditional Chinese medicine.

Mechanical analysis of the single microparticle motion in blood vessel / 医用生物力学

Objective To analyze the force condition of a single microparticle in blood vessel and the factors that influencing its motion. Method The microparticles in blood vessel during targeted drug delivery were studied, and the fluid flow in blood vessel was simplified as the Poiseuille flow in parallel plate flow chamber. Specific methods for calculating each force subjected on the single microparticle in the flow field were analyzed. The motion equations of the single microparticle were determined through calculation of its force balance and torque balance. The relationship between the force subjected on the single microparticle and the particle diameter/flow rate as well as the critical motion conditions of the particle diameter and flow rate were obtained by numerical calculation. Results The single microparticle was more subjected to the motion of rolling, sliding and ascending with the increase of flow rate and particle diameter. In flow rate and particle diameter diagrams, the critical curve of ascending motion located above that of sliding motion, while the rolling curve was located at the bottom.Conclusions The microparticle will not do the ascending motion under the condition of blood flow rate in human. As the blood flow rate reduces, the motion of microparticle with given diameter will be transfered from sliding to rolling, and will be entirely still under the condition of elastic deformation. Therefore, the proper selection of mircoparticle diameter and its surface adhesivity is critical for the drug particle to transport to the target location.

Evaluation of Dermatological Disorders Caused by Anti-neoplastic Agents with an Adverse Event Spontaneous Reporting Database / 医薬品情報学

<b>Introduction</b>: Dermatological disorders are one of the adverse events caused by cancer chemotherapy and are a dose-limiting factor for some anti-neoplastic agents.  The severe symptoms associated with these disorders affect the patients’ quality of life (QOL).  Early countermeasures for the onset of dermatological disorders associated with anti-neoplastic agent administration might be important.<br><b>Materials and Methods: </b>We analyzed the occurrences of dermatological disorders after administration of an anti-neoplastic agent in the Food and Drug Administration Adverse Event Reporting System (FAERS), and compared the adverse event (AE) reporting ratio of the total reports.  In addition, we studied the association between anti-neoplastic agents and dermatological disorders using cluster analysis.  Reports for 15 anti-neoplastic agents (4 anti-neoplastic agents and 11 molecular target drugs) were analyzed.<br><b>Results: </b>After excluding duplicate data in FAERS, 6,157,897 reports were analyzed.  The number of reports that showed a dermatological disorder was 534,934.  The reporting ratio of hand-foot syndrome with sorafenib and capecitabine was 11.20% and 7.05%, respectively.<br><b>Conclusions: </b>We set the cluster number at six; cluster features obtained were as follows: (1) the reporting ratio of hand-foot syndrome was especially high, followed by the reporting ratio of rash, (2) the reporting ratio of rash and erythema was high.  Similar anti-neoplastic agents may demonstrate similar occurrence tendencies of AEs and cluster features.  Further studies are required to draw conclusions over these findings.  Information services based on the feature of each cluster might be useful to improve patient QOL at the clinical site.

Promise of Neurorestoration and Mitochondrial Biogenesis in Parkinson's Disease with Multi Target Drugs: An Alternative to Stem Cell Therapy

There is an unmet need in progressive neurodegenerative diseases such as Parkinson's and Alzheimer's diseases. The present therapeutics for these diseases at best is symptomatic and is not able to delay disease or possess disease modifying activity. Thus an approach to drug design should be made to slow or halt progressive course of a neurological disorder by interfering with a disease-specific pathogenetic process. This would entail the ability of the drug to protect neurons by blocking the common pathway for neuronal injury and cell death and the ability to promote regeneration of neurons and restoration of neuronal function. We have now developed a number of multi target drugs which possess neuroprotective, and neurorestorative activity as well as being able to active PGC-1alpha (peroxisome proliferator-activated receptor gamma coactivator-1alpha), SIRT1 (NAD-dependent deacetylase protein) and NTF (mitochondrial transcription factor) that are intimately associated with mitochondrial biogenesis.

A case of no small cell lung carcinoma with leptomeningeal metastasis by elrotinib succeeded

<b>Introduction</b>: It is said that molecular target agents are more durable than cytotoxicic ones, although they have their own specific side effects. We experienced a case of non-small cell lung cancer with leptomeningeal metastasis and she had molecular target agents, she had palliation of symptom and prolongation of survival time. <b>Case</b>: Patient is 76 years old Japanese woman without smoking history. In April 2010 speech and gate disturbance was appeared on her, she was examined by CT and MRI, these revealed lung cancer, intrapulmonary metastasis, lymph nodal involvement, leptomeningeal metastasis, brain metastasis, and spinal bone metastasis in vertebras (T1bN1M1b, Stage IV). Symptoms such as gate disturbance, decrease of oral intake, drowsiness was regression rapidly, so patient and family decided discharge to go to home. She started to take elrotinib 100 mg on yth May. at home. She took elrotinib 150 mg since 6th June 2010 until July 2011 on her death. 2 weeks after administration of elrotinib she came to be able to eat and get up. On 6th August 2010 after administration of elrotinib primary lesion of lung cancer showed PR by CT, leptomeningeal and brain metastases showed SD by MRI. Grade 2 of skin rashu was manageable with topical corticosteroids. The remaining days from a diagnosis of the metastasis to lung cancer with leptomeningeal metastasis are reported with around three months. A symptom was relieved by the dosage of erlotinib,and there was not a serious side effect, and the patient could survive for one year and 5 months.

Feasibility of promoting blood circulation by removing blood stasis in target interfering ADUB endometrial hyperplasia / 中华中医药杂志

Objective:To observe the feasibility of promoting blood circulation by removing blood stasis in target interfering ADUB endometrial hyperplasia.Methods:Endometrial hyperplasia model was established,and the rats were divided into normal group(group A),model group(group B),small,middle and large dosage groups of Chinese drugs(C group,D group,E group,respectively).To observe uterus humid weight,uterus index,morphological change of endometria and expression of VEGF before and after treatment.In addition,30 cases of Anovulatory dysfunctional uterine bleeding were selected and given intrauterine injection of Qumozhibeng Cream twice in the first week after menstrual period,the change of menstrual blood amount were observed after applying medicine for one month,three months and six months.Results:After treatment,the uterus humid weight and uterus index decreased(P

Glycogen synthase kinase-3:an emerging therapeutic target for Alzheimers disease / 中国药理学通报

Glycogen synthase kinase-3(GSK3)is a fascinating serine/threonine protein kinase which exists in cells generally.GSK3 activity is regulated by phosphorylation,protein complex formation,and its intracellular localization.GSK3 regulates many functions including cell survival and apoptosis,structure and motility,intracellular signaling pathways and so on.It is very important to keep the activity of GSK3.GSK3 has been linked to all of the primary abnomalities associated with AD.It is very important to study the inhibition of GSK3 as a therapeutic approach to treat AD.All the studies suggest that GSK3 is a promising therapeutic target for AD.