Long-Term Immunogenicity and In Vitro Prophylactic Protective Efficacy of M. tuberculosis Fusion Protein DR2 Combined with Liposomal Adjuvant DIMQ as a Boosting Vaccine for BCG.

The resuscitation of dormant Mycobacterium tuberculosis is an important cause of adult tuberculosis (TB) transmission. According to the interaction mechanism between M. tuberculosis and the host, the latency antigen Rv0572c and region of difference 9 (RD9) antigen Rv3621c were selected in this study to prepare the fusion protein DR2. Stimulating clinically diagnosed active tuberculosis infections (i.e., TB patients), latent tuberculosis infections, and healthy controls confirmed that T lymphocytes could recognize DR2 protein in the peripheral blood of TB-infected individuals more than subcomponent protein. The DR2 protein was then emulsified in the liposome adjuvant dimethyl dioctadecyl ammonium bromide, and imiquimod (DIMQ) was administered to C57BL/6 mice immunized with Bacillus Calmette-Guérin (BCG) vaccine to evaluate their immunogenicity. Studies have shown that DR2/DIMQ, a booster vaccine for BCG primary immunization, can elicit robust CD4+ Th1 cell immune response and predominant IFN-γ+ CD4+ effector memory T cells (TEM) subsets. Furthermore, the serum antibody level and the expression of related cytokines increased significantly with the extension of immunization time, with IL2+, CD4+, or CD8+ central memory T cells (TCM) subsets predominant in the long term. This immunization strategy showed matched prophylactic protective efficacy by performing in vitro challenge experiment. This result provides robust evidence that the novel subunit vaccine prepared by fusion protein DR2 combined with liposomal adjuvant DIMQ is a promising TB vaccine candidate for further preclinical trials as a booster vaccine for BCG.

Research progress on the treatment of advanced prostate cancer with Olaparib.

Prostate cancer (PCa) is one of the most common malignancies in men worldwide, and metastatic castrate-resistant prostate cancer (mCRPC) has shown a poor prognosis. Although chemotherapy and androgen deprivation therapy (ADT) have improved clinical outcomes, the median survival (MS) of patients with mCRPC is still less than 2 years. With the development of poly adenosine diphosphate-ribose polymerase inhibitor (PARPi), the treatment strategy for patients with mCRPC has markedly evolved. Olaparib, a type of PARPi that can selectively induce synthetic lethality in cancer cells with homologous recombination (HR) deficiencies, was the first type of PARPi approved for treating patients with mCRPC harboring mutations in HR repair (HRR) genes. This review discusses and summarizes the latest progress on therapeutic mechanisms, monotherapy, combination therapy, and adverse events of Olaparib.

The Effectiveness and Safety of Cinobufotalin Injection as an Adjunctive Treatment for Lung Cancer: A Meta-Analysis of Randomized Controlled Trials.

Cinobufotalin injection is a water-soluble preparation extracted from the skin secretion of Bufo bufo gargarizans Cantor or B. melanotictus Schneider, which has been widely used as an adjuvant treatment in lung cancer patients. This study aimed to evaluate the clinical efficacy and safety of cinobufotalin (PubChem CID: 259776) injection as an adjunctive treatment for lung cancer. We designed a meta-analysis that performed following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We aim to include randomized controlled trials by systematically searching the PubMed, EMBASE, CNKI, Wanfang database, VIP, CBM, the Cochrane Central Register of Controlled Trials, and Chinese Clinical Trial Registry from inception to Mar 1, 2020, comparing the difference between the use of cinobufotalin injection as an adjunctive treatment and a control group without cinobufotalin injection. The objective response rate (ORR) and quality of life (QOL) will be defined as the primary outcomes, and the disease control rate (DCR) and adverse events will be defined as the secondary outcomes. We included 21 articles with 1735 cases of lung cancer patients. Comparison results show that combining with cinobufotalin injection can improve ORR (OR = 1.77, 95% CI [1.43, 2.21], P < 0.001), with low heterogeneity (P = 0.94, I 2 = 0%); DCR (OR = 2.20, 95% CI [1.70, 2.85], P < 0.001), with low heterogeneity (P = 0.60, I 2 = 0%); KPS score (OR = 3.10, 95% CI [2.23, 4.32], P < 0.001), with low heterogeneity (P = 0.85, I 2 = 0%); and the effect of pain relief (OR = 2.68, 95% CI [1.30, 5.55], P = 0.008), with low heterogeneity (P = 0.72, I 2 = 0%). Low-to-moderate evidence shows that cinobufotalin injection combined with chemotherapy can significantly increase ORR, DCR, QOL, and the effect of pain relief. Meanwhile, cinobufotalin injection did not bring additional adverse events such as hematological toxicity, gastrointestinal toxicity, cardiotoxicity, hepatotoxicity, and nephrotoxicity; however, multicenter, large-sample, high-quality clinical research results are still needed to reveal the therapeutic effect of cinobufotalin injection in small-cell lung cancer (PROSPERO registration number: CRD42020170052).

Chemotherapy regimens containing taxanes or fluorouracil in nasopharyngeal carcinoma: Which better?

OBJECTIVES: The efficacy of various chemotherapy regimens in nasopharyngeal carcinoma (NPC) remains under debate. We compared the efficacy and toxicity of a taxane-based regimen and regimen including fluorouracil in NPC. MATERIALS AND METHODS: Eight-hundred and six patients with stage II-IVB NPC from four institutions in China were pair-matched (1:1 ratio) to the cisplatin plus fluorouracil (PF) group or cisplatin plus taxanes (TP) group using eight clinical factors. Overall survival (OS), disease-free survival (DFS), locoregional relapse-free survival (LRRFS) and distant metastasis-free survival (DMFS) were assessed using the Kaplan-Meier method and Cox regression model. Toxicities were assessed in all patients. RESULTS: Three-year DFS was significantly better in the TP group than PF group (82.5% vs. 72.7%, P=0.002), with no significant difference in OS, LRRFS or DMFS. TP led to significantly better DFS compared to PF in the subgroups advanced stage NPC, patients aged ≤45-years-old and female patients. In multivariate analysis, chemotherapy regimen was an independent prognostic factor for DFS [hazard ratio, 0.591, 95% CI 0.444-0.786, P=0.000]. Grade 3-4 leukopenia, neutropenia and anemia were significantly more common in the TP group; grade 3-4 mucositis, vomiting, vasculitis and diarrhea were more common in the PF group. CONCLUSION: Taxane-based regimens have a higher efficacy in NPC than regimens including fluorouracil, especially in patients with advanced stage, patients aged≤45-years-old and female patients.

Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma : A matched-pair multicenter analysis of outcomes.

PURPOSE: The benefit of adjuvant chemotherapy (AC) in locoregionally advanced nasopharyngeal carcinoma (NPC) is controversial. This study compared concurrent chemoradiotherapy plus AC (CCRT/AC) with CCRT. METHODS: Pair-matched analysis based on eight clinicopathological features of 244 patients treated with platinum-based CCRT/AC or CCRT alone was performed. Survival outcomes were assessed using the Kaplan-Meier method and log-rank test. Toxicities and response rates were compared using Fisher's exact test. RESULTS: Four-year overall survival, progression-free survival, distant failure-free survival, and locoregional failure-free survival were 72 %, 61 %, 71 %, and 81 %, respectively, for the CCRT arm, compared to 74 % (hazard ratio, HR 0.89; 95 % confidence interval, CI 0.64-1.23; P = 0.474), 62 % (HR 0.91, 95 % CI 0.68-1.20, P = 0.489), 73 % (HR 0.84, 95 % CI 0.59-1.18, P = 0.316), and 84 % (HR 0.84, 95 % CI 0.52-1.24, P = 0.323), respectively, for the CCRT/AC arm. Cox multivariate regression analysis demonstrated AC was not an independent prognostic factor. Overall, there was a higher incidence of grade 3-4 toxicities in the CCRT/AC arm. The most common grade 3-4 adverse events in the CCRT/AC arm were vomiting (27 %), nausea (43 %), leukopenia/neutropenia (23 %), thrombocytopenia (8.8 %), and anemia (6.2 %). CONCLUSION: Addition of AC to CCRT increased toxicities but did not improve survival in locoregionally advanced NPC.