Emerging Opportunities for Combining Locoregional Therapy with Immune Checkpoint Inhibitors in Hepatocellular Carcinoma.

PURPOSE OF REVIEW: Immunotherapy shows great promises in solid tumors. Locoregional therapy can promote systemic immune response in hepatocellular carcinoma (HCC). The combination of locoregional therapy and immune checkpoint inhibitors (ICIs) activates a synergistic effect that can enhance the potency of anti-tumor immunity. This review aims to summarize the underlying mechanisms of locoregional therapy combined with ICIs and their applications in clinical settings. RECENT FINDINGS: The characteristics of high invasiveness and refractoriness of HCC are what limit the outcomes of treatments. Sorafenib provides an additional treatment option for extrahepatic spread and vascular invasion, making long-term survival possible for patients with advanced HCC to some degree. However, its shortcomings of low response rate and high toxicity result in limited applications in clinical practice. Immunotherapy is a promising emerging therapy with great prospect in HCC, but the self-tolerance of HCC constrains the effectiveness of ICIs. Consequently, the efficacy of single immunotherapy is unsatisfactory. Locoregional therapy can not only destroy primary tumors but also stimulate the release of neoplasm antigens to increase the efficiency of immune response in HCC. Locoregional therapy combined with ICIs may have an amplification effect on immune response. Locoregional therapy plays a vital role in stimulating anti-tumor immune response. The combination of locoregional therapy and ICIs has a synergistic effect on anti-tumor immunity.

IGF-1 alleviates serum IgG-induced neuronal cytolysis through PI3K signaling in children with opsoclonus-myoclonus syndrome and neuroblastoma.

BACKGROUND: Opsoclonus-myoclonus syndrome (OMS) is a rare neurological disorder, usually accompanied by neuroblastoma (NB). There is no targeted treatment and animal model of OMS. We aimed to investigate whether insulin-like growth factor 1 (IGF-1)/phosphoinositide 3-kinase (PI3K) signaling alleviates neuronal cytolysis in pediatric OMS. METHODS: Cultured rat cerebral cortical neurons and cerebellar neurons were incubated with sera or IgG isolated from sera of children with OMS and NB. Cytolysis and PI3K expression were measured by the lactate dehydrogenase assay and enzyme-linked immunosorbent assay, respectively. Using inhibitors and activators, the effects of IGF-1 and PI3K on cytolysis were investigated. RESULTS: The incubation of sera or IgG from children with OMS and NB increased cytolysis in not only cerebellar neurons, but also cerebral cortical neurons. Furthermore, the IGF-1 receptor antagonist NVP-AEW541 exaggerated cytolysis in children with OMS and NB. IGF-1 alleviated cytolysis, which was blocked by the PI3K inhibitor LY294002. Additionally, sera or IgG from children with OMS and NB compensatively elevated PI3K expression. LY294002 exacerbated cytolysis; whereas, the PI3K activator 740 Y-P suppressed cytolysis. CONCLUSION: IGF-1/PI3K signaling alleviates the cytolysis of cultured neurons induced by serum IgG from children with OMS and NB, which may be innovation therapy targets.

[Methods of removing failed implants].

Implant restoration has become one of the most regular methods of restoring dentition defect or edentulous. Implant placement and osseointegration are partly unreserved (fracture, implant is not in the correct three-dimensional position and cannot be repaired, peri-implantitis-affected nonmobile implants) need to be removed. This article reviews the different methods of removing implants and discusses the limitations of each method, as well as the complications that may occur during the procedure.

Revealing chemical processes and kinetics of drug action within single living cells via plasmonic Raman probes.

Better understanding the drug action within cells may extend our knowledge on drug action mechanisms and promote new drugs discovery. Herein, we studied the processes of drug induced chemical changes on proteins and nucleic acids in human breast adenocarcinoma (MCF-7) cells via time-resolved plasmonic-enhanced Raman spectroscopy (PERS) in combination with principal component analysis (PCA). Using three popular chemotherapy drugs (fluorouracil, cisplatin and camptothecin) as models, chemical changes during drug action process were clearly discriminated. Reaction kinetics related to protein denaturation, conformational modification, DNA damage and their associated biomolecular events were calculated. Through rate constants and reaction delay times, the different action modes of these drugs could be distinguished. These results may provide vital insights into understanding the chemical reactions associated with drug-cell interactions.