Progress on clinical trials of common gastrointestinal cancer drugs in China from 2012 to 2021 / 中华肿瘤杂志

Objective: Systematically summarize the research progress of clinical trials of gastric cancer oncology drugs and the overview of marketed drugs in China from 2012 to 2021, providing data and decision-making evidence for relevant departments. Methods: Based on the registration database of the drug clinical trial registration and information disclosure platform of Food and Drug Administration of China and the data query system of domestic and imported drugs, the information on gastric cancer drug clinical trials, investigational drugs and marketed drugs from January 1, 2012 to December 31, 2021 was analyzed, and the differences between Chinese and foreign enterprises in terms of trial scope, trial phase, treatment lines and drug type, effect and mechanism studies were compared. Results: A total of 114 drug clinical trials related to gastric tumor were registered in China from 2012 to 2021, accounting for 3.7% (114/3 041) of all anticancer drug clinical trials in the same period, the registration number showed a significant growth rate after 2016 and reached its peak with 32 trials in 2020. Among them, 85 (74.6%, 85/114) trials were initiated by Chinese pharmaceutical enterprise. Compared with foreign pharmaceutical enterprise, Chinese pharmaceutical enterprise had higher rates of phase I trials (35.3% vs 6.9%, P=0.001), but the rate of international multicenter trials (11.9% vs 67.9%, P<0.001) was relatively low. There were 76 different drugs involved in relevant clinical trials, of which 65 (85.5%) were targeted drugs. For targeted drugs, HER2 is the most common one (14 types), followed by PD-1 and multi-target VEGER. In the past ten years, 3 of 4 marketed drugs for gastric cancer treatment were domestic and included in the national medical insurance directory. Conclusions: From 2012 to 2021, China has made some progress in drug research and development for gastric carcinoma. However, compared with the serious disease burden, it is still insufficient. Targeted strengthening of research and development of investment in many aspects of gastric cancer drugs, such as new target discovery, matured target excavating, combination drug development and early line therapy promotion, is the key work in the future, especially for domestic companies.

Technical considerations on the study and evaluation of the biosimilars' immunogenicity / 中国药学杂志

OBJECTIVE: To evaluate the immunogenicity of biosimilars. METHODS: Non-clinical and clinical studies carried out in accordance with the guidelines in immunological characteristics and immunogenicity of biosimilars should focus on the production of anti-drug antibodies and detection of drug-resistant properties, immune complexes and their potential effects on pharmacodynamics/pharmacokinetics. Assays for immunogenicity of biological agents mainly include enzyme linked immunosorbent assay (ELISA), radioimmunoassay, surface plasm on resonance method, enzyme linked immunospot assay, immuno-PCR method, cell proliferation assay, etc. RESULTS AND CONCLUSION: Biosimilars immunogenicity should be comprehensively interpreted based on both the preclinical/clinical evaluation results and the prevalence of clinical adverse events.

Technical considerations on non-clinical study and evaluation for biosimilar products / 中国药学杂志

OBJECTIVE: To evaluate biosimilar products focus on the similarities in the quality, safety and eificacy between the candidate and reference products. METHODS: Comparative non-clinical studies should be conducted and stepwise development should be carried out to demonstrate the similarity in non-clinical study for the candidate and reference products. Usually the necessity and content of in vivo study are dependent on the results of previous comparative studies in vitro. RESULTS AND CONCLUSION: Determination of the non-clinical similarity should be based on the statistical analysis of the candidate and reference products. Evaluation for toxicity similarities can focus on toxicity profile in types and extent. The non-clinical similarities will affect the strategy of clinical trial for biosimilars.

Effects of programmed cell death on human dental follicle cells and changes of programmed cell death under different hydrostatic pressures / 华西口腔医学杂志

<p><b>OBJECTIVE</b>Tooth eruption requires the presence of the dental follicle (DF) around the unerupted tooth. This study is to investigate programmed cell death on human dental follicle cells and changes of programmed cell death under different hydrostatic pressures: 0, 50 and 100 kPa.</p><p><b>METHODS</b>Human dental follicles from third mandibular molars were surgically removed from adolescents who need for orthodontics treatment after informed content, then trypsinized and cultured. Human dental follicle cells were divided into three groups according to different hydrostatic pressures: 0, 50 and 100 kPa and their programmed cell death were labeled by using TdT-medi-ated-dUTP nick and labeling (TUNEL).</p><p><b>RESULTS</b>Dental follicle cells cultured were elongate shape and exhibited fibroblastic characteristics. Compared with 0 kPa, programmed cell death cells on human dental follicle cells were increased 0.23% and 31.65% under 50 kPa and 100 kPa hydrostatic pressures respectively. 100 kPa group increased significantly (P < 0.01).</p><p><b>CONCLUSION</b>It suggested that programmed cell death occured in human dental follicle cells cultured in vitro and was influenced by different hydrostatic pressures. Hydrostatic pressure may improve tooth erup-tion through dental follicle.</p>

The protective effect of vitamin E against oxidative damage caused by formaldehyde in the testes of adult rats / 亚洲男科学杂志(英文版)

<p><b>AIM</b>To investigate the effect of formaldehyde (FA) on testes and the protective effect of vitamin E (VE) against oxidative damage by FA in the testes of adult rats.</p><p><b>METHODS</b>Thirty rats were randomly divided into three groups: (1) control; (2) FA treatment group (FAt); and (3) FAt + VE group. FAt and FAt + VE groups were exposed to FA by inhalation at a concentration of 10 mg/m(3) for 2 weeks. In addition, FAt + VE group were orally administered VE during the 2-week FA treatment. After the treatment, the histopathological and biochemical changes in testes, as well as the quantity and quality of sperm, were observed.</p><p><b>RESULTS</b>The testicular weight, the quantity and quality of sperm, the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione (GSH) were significantly decreased whereas the level of malondialdehyde (MDA) was significantly increased in testes of rats in FAt group compared with those in the control group. VE treatment restored these parameters in FAt + VE group. In addition, microscopy with hematoxylin-eosin (HE) staining showed that seminiferous tubules atrophied, seminiferous epithelial cells disintegrated and shed in rats in FAt group and VE treatment significantly improved the testicular structure in FAt + VE group.</p><p><b>CONCLUSION</b>FA destroys the testicular structure and function in adult rats by inducing oxidative stress, and this damage could be partially reversed by VE.</p>

Clinical research on unilateral extraction for moderate crowding / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To clinically investigate the results of unilateral extraction in the treatment of special moderate crowding cases.</p><p><b>METHODS</b>22 patients with harmonic profile and moderate crowding were selected and treated by unilateral extraction with Edgewise technique. The patients crowding was 6 - 9 mm and focused on one side of the arch. 22 patients with moderate crowding were treated by bilateral extraction as control.</p><p><b>RESULTS</b>22 patients have been treated successfully within 18 months. Crowding was completely resolved. Midline coincidence was basically maintained.Good intercuspation was achieved. There is no significant difference in dental arch symmetry between unilateral extraction and bilateral extraction (P > 0.05).</p><p><b>CONCLUSION</b>Unilateral extraction can be successful in the treatment of special moderate crowding cases.</p>

Sex-difference on flutamide metabolism in rat liver microsomal cytochrome P450 1A2 / 药学学报

<p><b>AIM</b>To assess the sex-difference on flutamide metabolism in rat liver microsomes useing rat cytochrome P450, 1A2, inhibitory monoclonal antibody.</p><p><b>METHODS</b>Liver microsomes were prepared from male or female rats. Protein concentration and total cytochrome P450 content were determined. Incubation mixture included liver microsomes (1.0 nmol.L-1), reduced form of nicotinamide adenine dinucleotide phosphate (NADPH, 0.1 nmol.L-1), CYP1A2 (1:400) and flutamide (2 mg.L-1). The incubation time was 30 min. The concentration of flutamide and its major metabolite 2-hydroxyflutamide were analyzed by reverse high-performance liquid chromatography. The mobile phase was a mixture of methanol-acetonitrile-water-diethylether (40:20:35:1) with methyltestosterone as internal standard. The detection wavelength was 234 nm. The reaction mixture was extracted with acetic ether 4 mL. Sex-difference on flutamide metabolism was expressed as the difference between the concentration ratio of 2-hydroxyflutamide to flutamide in male and female rat liver microsomes.</p><p><b>RESULTS</b>The recoveries of flutamide and 2-hydroxyflutamide for the proposed method were more than 75%. The formation of 2-hydroxyflutamide from flutamide was inhibited by CYP1A2 antibodies (1:400) in male and female rat liver microsome for 30 min of incubation time, but the inhibition of flutamide metabolism in female rat was stronger than that in male. The concentration ratios of 2-hydroxyflutamide to flutamide were (1.5 +/- 0.6) and (0.9 +/- 0.4) in male and female rat liver microsomes, respectively (P < 0.01).</p><p><b>CONCLUSION</b>The results indicate that the activity of male rat CYP1A2 is higher than that of the female rat. There is difference in sex-related rate of flutamide metabolism in rat liver microsomes.</p>