Gendicine (recombinant human p53 adenovirus), developed by Shenzhen SiBiono GeneTech Co. Ltd., was approved in 2003 by the China Food and Drug Administration (CFDA) as a first-in-class gene therapy product to treat head and neck cancer, and entered the commercial market in 2004. Gendicine is a biological therapy that is delivered via minimally invasive intratumoral injection, as well as by intracavity or intravascular infusion. The wild-type (wt) p53 protein expressed by Gendicine-transduced cells is a tumor suppressor that is activated by cellular stress, and mediates cell-cycle arrest and DNA repair, or induces apoptosis, senescence, and/or autophagy, depending upon cellular stress conditions. Based on 12 years of commercial use in >30,000 patients, and >30 published clinical studies, Gendicine has exhibited an exemplary safety record, and when combined with chemotherapy and radiotherapy has demonstrated significantly higher response rates than for standard therapies alone. In addition to head and neck cancer, Gendicine has been successfully applied to treat various other cancer types and different stages of disease. Thirteen published studies that include long-term survival data showed that Gendicine combination regimens yield progression-free survival times that are significantly longer than standard therapies alone. Although the p53 gene is mutated in >50% of all human cancers, p53 mutation status did not significantly influence efficacy outcomes and long-term survival rate for Ad-p53-treated patients. To date, Shenzhen SiBiono GeneTech has manufactured 41 batches of Gendicine in compliance with CFDA QC/QA requirements, and 169,571 vials (1.0 × 10 vector particles per vial) have been used to treat patients. No serious adverse events have been reported, except for vector-associated transient fever, which occurred in 50-60% of patients and persisted for only a few hours. The manufacturing accomplishments and clinical experience with Gendicine, as well as the understanding of its cellular mechanisms of action and implications, could provide valuable insights for the international gene therapy community and add valuable data to promote further developments and advancements in the gene therapy field.

Background: Patent ductus arteriosus (PDA) is a dramatically harmful disease in the neonatal period, in particular common in preterm infants, and our study was to determine related factors of PDA in preterm infants.Methods: A comprehensive literature review was conducted in PubMed, EMBASE, and Web of Science. The pooled odds ratio and standard mean difference were calculated to compare dichotomous and continuous variables, respectively. In addition, we also assessed the heterogeneity and publication bias and carried out sensitivity analysis for each related factor.Results: We included 45 studies with 87,419 individuals. After the primary analysis and a series of adjustments, results showed chorioamnionitis, lower gestational age, lower birth weight, bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, respiratory distress syndrome, sepsis, surfactant treatment, ventilation, and lower platelet count had a positive correlation with PDA, while small for gestational age decreased the incidence of PDA in preterm infants. Besides, premature rupture of membranes, preeclampsia, antenatal steroids, male gender, mean platelet volume, and platelet distribution width were found to have no statistically significant relationship with PDA.Conclusion: Preterm infants with more immature characteristics generally have a higher likelihood to develop PDA. The prevention, diagnosis, and management of PDA may depend on these results, and effective measures can be taken accordingly.

Atractylodes macrocephala polysaccharide (AMP) can enhance antioxidant defense and anti-inflammation, as the tolerance levels of AMP in aquaculture is important for additive utilization. However, the tolerance dose of AMP is unknown. We assess the tolerance levels of AMP in juvenile largemouth bass (3.38 ± 0.11 g) by feeding them a 0, 400, 4000, or 8000 mg/kg AMP supplemented diet for 10 weeks. The 400 mg/kg AMP dose increased growth performance. The Nrf2/Keap1 signaling pathway was activated, as indicated by Keap1 and Nrf2 protein levels in the liver. Enhanced activity of antioxidant enzymes (SOD, GPx), together with increased mRNA levels of antioxidant genes (sod, gpx) and decreased accumulation of reactive oxygen species (ROS) and MDA, was found in the liver, implying the antioxidant effect of AMP. Nutrient absorption was enhanced by AMP, as reflected by the increased length of intestinal villi and microvilli. However, 4000 and 8000 mg/kg AMP induced oxidant stress, as indicated by increased plasma ALT and AST content and decreased mRNA levels of antioxidant genes (sod, gpx) in the liver and intestinal tissues. Inflammatory reactions were also induced by high doses of AMP, as reflected by enhanced levels of pro-inflammatory cytokines (tnfα, nfκb) in the liver, intestinal, and kidney tissues and inhibited levels of anti-inflammatory cytokines (tgfβ, iκb). Histological analysis reveals inflammatory cell infiltration and tissue damage. Thus, the safe tolerance margin of AMP supplement for largemouth bass was 400–4000 mg/kg.

PurposeHyperthermia is a mechanistically plausible partner with chemotherapy, although many of the underlying molecular mechanisms of this combination treatment are not yet properly understood. Preclinical studies suggest that there is potential synergy with gemcitabine and that provides the basis for retrospective analysis of a clinical series combining these treatment modalities for patients with advanced pancreatic cancer.Patients and MethodsTwenty-nine chemotherapy-naive patients with locally advanced or metastatic pancreatic carcinoma with malignant ascites were treated with intraperitoneal cisplatin 30 mg/m2 and gemcitabine 800 to 1,000 mg/m2 intravenously on days 1, 8, and 15 every 28 days until tumor progression. Patients also received regional hyperthermia treatment (41 to 42°C) on the upper abdomen two times per week from days 1 to 21.ResultsIn all, 83 cycles of chemotherapy were administered and were generally well tolerated. No patients had a complete response, 13 had a partial response, seven had stable disease, and 9 had progressive disease. Mean progression-free survival and overall survival were 119 ± 61days and 195 ± 98 days, respectively.ConclusionThis study provides preliminary evidence that the treatment approach of combined systemic and intraperitoneal chemotherapy plus hyperthermia is well tolerated, is active, and has an acceptable survival profile for patients with stage IV pancreatic cancer and ascites.

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