TACE-sorafenib side effects were acceptable, and this treatment may improve overall survival in patients with HCC with first-order or lower-branch PVTT when compared with patients who underwent TACE alone.
PurposeTo investigate the efficacy and safety of transarterial chemoembolization (TACE) combined with lenvatinib plus PD-1 inhibitor (TACE-L-P) versus TACE combined with lenvatinib (TACE-L) for patients with advanced hepatocellular carcinoma (HCC).Materials and MethodsData of advanced HCC patients treated with TACE-L-P (TACE-L-P group) or TACE-L (TACE-L group) from January 2019 to December 2020 were prospectively collected and retrospectively analyzed. The differences in overall survival (OS), progression-free survival (PFS), tumor responses (based on modified Response Evaluation Criteria in Solid Tumors) and adverse events (AEs) were compared between the two groups. Potential factors affecting OS and PFS were determined.ResultsA total of 81 patients were included in this study. Among them, 41 received TACE-L-P and 40 received TACE-L. The patients in TACE-L-P group had prolonged OS (median, 16.9 vs. 12.1 months, P=0.009), longer PFS (median, 7.3 vs. 4.0 months, P=0.002) and higher objective response rate (56.1% vs. 32.5%, P=0.033) and disease control rate (85.4% vs. 62.5%, P=0.019) than those in TACE-L group. Multivariate analyses revealed that the treatment option of TACE-L, main portal vein invasion and extrahepatic metastasis were the independent risk factors for OS, while TACE-L and extrahepatic metastasis were the independent risk factors for PFS. In subgroup analyses, a superior survival benefit was achieved with TACE-L-P in patients with extrahepatic metastasis or tumor number >3 but not in those with main portal vein invasion. The incidence and severity of AEs in TACE-L-P group were comparable to those in TACE-L group (any grade, 92.7% vs. 95.0%, P=1.000; grade 3, 36.6% vs. 32.5%, P=0.699).ConclusionTACE-L-P significantly improved survival over TACE-L with an acceptable safety profile in advanced HCC patients, especially those with extrahepatic metastasis or tumor number >3 but without main portal vein invasion.
Immunotherapy has revolutionized oncology remarkably and gained great improvements in cancer therapy. However, tumor immunotherapy still encounters serious challenges, especially certain tumors barely respond to immunotherapy. The lack of immunogenicity and subsequent insufficient antitumor immune activation is a pivotal reason. Here, a general introduction and the strengthening strategies of immunogenicity of a tumor for enhanced immunotherapy are reviewed. Specifically, nanotechnology nowadays is playing important roles in increasing the antitumor efficacy of various treatments, including immunotherapy. This review highlights how nanomedicines integrating one or more anticancer therapeutic methods (e.g., cancer vaccines, chemotherapy, phototherapy, and radiotherapy) to increase the tumor immunogenicity for rousing T cell related immune responses and achieving inspiring antitumor efficacy. Given the sophisticated immune evasion mechanisms, rational designed nanodrugs with combinational formulations are summarized to improve therapeutic efficacy in synergistic ways. Nanoplatforms taking advantage of the distinct features of tumor tissue or tumor cell with stimuli-responsiveness and targeting functions are introduced to accelerate tumor accumulation of drugs successfully and greatly promote therapeutic efficacy with low-dose administration and programmed drug release. Finally, the related challenges and personal perspectives of nanomedicines for tumor immunotherapy are concluded.
In this review, we explored the progress of the pathogenesis of Kümmell's disease intravertebral vacuum. Using different expressions of the same disease including ‘Kümmell's disease’, ‘avascular necrosis after vertebral compression fracture (VCF)’, ‘post-traumatic vertebral osteonecrosis’, ‘vertebral pseudarthrosis’, ‘intravertebral vacuum (cleft or gas)’, ‘delayed vertebral collapse’, ‘VCF nonunion’, and by conducting a search of the PubMed database, we analyzed the results to examine the pathogenesis of the intravertebral vacuum of Kümmell's disease after referring to pertinent literature on intravertebral vacuum of ischemic necrosis after VCF, and exploring the progress of pathogenesis of this disease. A number of discrepancies were identified within the pathogenesis of the intravertebral vacuum after VCF. There were statements such as avascular necrosis of the vertebral body, bone biomechanics, gas forming and other types of claims, all of which obtained clinical and biomechanical supporting evidence. Collectively, most of the researchers believe that Kümmell vertebral fracture syndrome was the comprehensive effect of multiple factors including osteoporosis, avascular necrosis of the vertebral body, and biomechanical changes following fracture. However, there are a number of discrepancies to be resolved and future studies are therefore needed.
Drug resistance, developed through multiple mechanisms, is a major hindrance to successful chemotherapy of tumor. Combination therapy of chemotherapeutic drugs and siRNA represents an emerging strategy which may improve anticancer effect by synergistic actions. In this study, triblock copolymer of poly(ethylene glycol)- block-poly(l-lysine)- block-poly aspartyl ( N-( N', N'-diisopropylaminoethyl)) (PEG-PLL-PAsp(DIP)) was synthesized for the first time to enable the codelivery of BCL-2 siRNA and DOX. The system is supposed to not only bypass drug efflux but also down-regulate the antiapoptotic gene and consequently confronting against chemoresistance as well. Moreover, the pH responsive ability of the codelivery system can prevent drug leakage during circulation and guarantee swift drug release at tumors. The codelivered siRNA serves to suppress the expression of antiapoptotic BCL-2 and hence sensitize the cancer cells to anticancer drugs and produce improved therapeutic effect. Consequently, the codelivery of BCL-2 siRNA and anticancer drug DOX serves as a promising strategy against drug resistance in chemotherapy.
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