IR792-MCN@ZIF-8-PD-L1 siRNA drug delivery system enhances photothermal immunotherapy for triple-negative breast cancer under near-infrared laser irradiation.

BACKGROUND: Despite extensive investigations on photothermal therapy, the clinical application is restricted due to poor stability, low therapeutic efficacy of photothermal therapy agents and its affinity loss in the multistep synthesis of delivery carriers. To address this, we designed an IR792-MCN@ZIF-8-PD-L1 siRNA (IM@ZP) nanoparticle drug delivery system. IM@ZP was prepared by in situ synthesis and physical adsorption, followed by characterization. Photothermal conversion ability of IM@ZP was assessed by irradiation of near-infrared (NIR) laser, followed by analysis of its effect on 4T1 cell viability, maturation of dendritic cells (DCs) and the secretion of related cytokines in vitro, and the changes of tumor infiltrating T cells and natural killer (NK) cells in vivo. Subcutaneous 4T1 tumor-bearing mouse and lung metastasis models were established to investigate the role of IM@ZP in killing tumor and inhibiting metastasis in vivo. RESULTS: IM@ZP was uniform nanoparticles of 81.67 nm with the characteristic UV absorption peak of IR792, and could effectively adsorb PD-L1 siRNA. Under the irradiation of 808 nm laser, IM@ZP exhibited excellent photothermal performance. IM@ZP could be efficiently uptaken by 4T1 cells, and had high transfection efficiency of PD-L1 siRNA. Upon NIR laser irradiation, IM@ZP effectively killed 4T1 cells, upregulated HSP70 expression, induced DC maturation and increased secretion of TNF-α and IL-6 in vitro. Moreover, in vivo experimental results revealed that IM@ZP enhanced photothermal immunotherapy as shown by promoted tumor infiltrating CD8 + and CD4 + T cells and NK cells, and inhibited tumor growth and lung metastasis. CONCLUSION: Together, biocompatible IM@ZP nanoparticles result in high photothermal immunotherapy efficiency and may have a great potential as a delivery system for sustained cancer therapy.

Effect of an Artificial Intelligence Clinical Decision Support System on Treatment Decisions for Complex Breast Cancer.

PURPOSE: To examine the impact of a clinical decision support system (CDSS) on breast cancer treatment decisions and adherence to National Comprehensive Cancer Center (NCCN) guidelines. PATIENTS AND METHODS: A cross-sectional observational study was conducted involving 1,977 patients at high risk for recurrent or metastatic breast cancer from the Chinese Society of Clinical Oncology. Ten oncologists provided blinded treatment recommendations for an average of 198 patients before and after viewing therapeutic options offered by the CDSS. Univariable and bivariable analyses of treatment changes were performed, and multivariable logistic regressions were estimated to examine the effects of physician experience (years), patient age, and receptor subtype/TNM stage. RESULTS: Treatment decisions changed in 105 (5%) of 1,977 patients and were concentrated in those with hormone receptor (HR)-positive disease or stage IV disease in the first-line therapy setting (73% and 58%, respectively). Logistic regressions showed that decision changes were more likely in those with HR-positive cancer (odds ratio [OR], 1.58; P < .05) and less likely in those with stage IIA (OR, 0.29; P < .05) or IIIA cancer (OR, 0.08; P < .01). Reasons cited for changes included consideration of the CDSS therapeutic options (63% of patients), patient factors highlighted by the tool (23%), and the decision logic of the tool (13%). Patient age and oncologist experience were not associated with decision changes. Adherence to NCCN treatment guidelines increased slightly after using the CDSS (0.5%; P = .003). CONCLUSION: Use of an artificial intelligence-based CDSS had a significant impact on treatment decisions and NCCN guideline adherence in HR-positive breast cancers. Although cases of stage IV disease in the first-line therapy setting were also more likely to be changed, the effect was not statistically significant (P = .22). Additional research on decision impact, patient-physician communication, learning, and clinical outcomes is needed to establish the overall value of the technology.

The combination therapy of transarterial chemoembolisation and sorafenib is the preferred palliative treatment for advanced hepatocellular carcinoma patients: a meta-analysis.

BACKGROUND: To compare the efficacy of three types of palliative therapy for advanced hepatocellular carcinoma (HCC), including transarterial chemoembolisation (TACE) monotherapy, sorafenib alone and their combination. METHODS: The databases of PubMed, Embase and Cochrane Library were retrieved. The odds ratio (OR) with its 95% confidence interval (CI) was used to investigate the binary variables, and the standardised mean difference (SMD) with its 95% CI was employed to evaluate the continuous variables. All statistical tests were performed by using Stata/SE, version 12.0. RESULTS: Thirty-one clinical studies, containing 5125 unique cases of patients with advanced HCC, were included. There were significant improvements in overall survival (OS) (pooled SMD = 2.54; 95% CI 1.74-3.34) and time to progression (TTP) (pooled SMD = 2.49; 95% CI 0.87-4.12) of the patients after receiving the combination therapy of TACE and sorafenib, compared to TACE monotherapy, and the OS in the combined treatment cohort was also longer than that in the sorafenib-alone cohort (pooled SMD = 2.92; 95% CI 1.72-4.13). The combination therapy group in comparison to the TACE group benefited a significantly increased overall response rate (ORR) (pooled OR = 2.61; 95% CI 1.43-4.77), 1-year (pooled OR = 2.96; 95% CI 1.71-5.14) and 2-year (pooled OR = 1.64; 95% CI 1.18-2.28) survival rates and reduced disease progression rate (DPR) (pooled OR = 0.47; 95% CI 0.33-0.68); in parallel, the ORR in the group was also significantly higher than that in the sorafenib-alone group (pooled OR = 3.62; 95% CI 1.28-10.22), although without a difference in the DPR (pooled OR = 0.28; 95% CI 0.05-1.48). In addition, we discovered that the 1-year (pooled OR = 1.39; 95% CI 0.84-2.29) and 2-year (pooled OR = 1.70; 95% CI 0.69-4.18) survival rates in the TACE monotherapy cohort were not significantly different to those in the sorafenib-alone cohort. CONCLUSION: The combination therapy is more effective than monotherapy in improving the prognostic outcomes of patients with advanced HCC. Therefore, we recommend it as the preferred treatment intervention for those patients.

Artificial Intelligence Treatment Decision Support For Complex Breast Cancer Among Oncologists With Varying Expertise.

PURPOSE: The aim of the current study was to assess treatment concordance and adherence to National Comprehensive Cancer Network breast cancer treatment guidelines between oncologists and an artificial intelligence advisory tool. PATIENTS AND METHODS: Study cases of patients (N = 1,977) who were at high risk for recurrence or who had metastatic disease and cell types for which the advisory tool was trained were obtained from the Chinese Society for Clinical Oncology cancer database (2012 to 2017). A cross-sectional observational study was performed to examine treatment concordance and guideline adherence among an artificial intelligence advisory tool and 10 oncologists with varying expertise-three fellows, four attending physicians, and three chief physicians. In a blinded fashion, each oncologist provided treatment advice on an average of 198 cases and the advisory tool on all cases (N = 1,977). Results are reported as rates and logistic regression odds ratios. RESULTS: Concordance for the recommended treatment was 0.56 for all physicians and higher for fellows compared with chief and attending physicians (0.68 v 0.54; 0.49; P = .001). Concordance differed by hormone receptor subtype-TNM stage, with the lowest for hormone receptor-positive human epidermal growth factor receptor 2/neu-positive cancers (0.48) and highest for triple-negative breast cancers (0.71) across most TNM stages. Adherence to National Comprehensive Cancer Network guidelines was higher for oncologists compared with the advisory tool (0.96 v 0.82; P < .003) and lower for fellows compared with attending physicians (0.93 v 0.98; 0.96; P = .04). CONCLUSION: Study findings reflect a complex breast cancer case mix, the limits of medical knowledge regarding optimum treatment, clinician practice patterns, and use of a tool that reflects expertise from one cancer center. Additional research in different practice settings is needed to understand the tool's scalability and its impact on treatment decisions and clinical and health services outcomes.

[Observation on therapeutic effects of combined acupuncture and medicine therapy and simple medication on renal hypertension of chronic kidney disease].

OBJECTIVE: To probe into a method for increasing clinical therapeutic effect on renal hypertension of chronic kidney disease. METHODS: One hundred and fifty-two cases were randomly divided into a combined acupuncture and medicine group and a medication group, 76 cases in each group. The combined acupuncture and medicine group were treated with acupuncture balance points "Jiangya" and "Shenbing" as main, combined with small dose of hypotensor, Irbesartan; and the medication group were treated with oral administration of Irbesartan and Fosinopril. Their clinical therapeutic effects were compared. RESULTS: After treatment of 4 weeks, 56.58% of the patients in the combined acupuncture and medicine group reached to the objective value [DBP < or = 84.96 mm Hg (1 mm Hg= 0.133 kPa)], and 53.95% of the patients in the medication group reached to the objective value, with no significant difference between the two groups (P > 0.05). After treatment of 8 weeks and 24 weeks, the blood pressure-decreasing effect in the combined acupuncture and medicine group was better than that of the medication group (P < 0.01). After treatment, protein in the urine decreased and blood creatinine reduced, the clearance rate of endogenous creatinine raised in the two groups, with very significant differences (P < 0.01). CONCLUSION: Acupuncture combined with small dose of medicine and simple medicine have a same therapeutic effect on renal hypertension of chronic kidney disease, but with prolongation of treatment time, the therapeutic effect and advantages of the combined acupuncture and medicine therapy were superior to the medication.