The combination of PD-1/PD-L1 inhibitor with CTLA-4 inhibitor for advanced non-small cell lung cancer(NSCLC) is presently a significant area of research, however its clinical application remains contentious. This meta-analysis aimed to assess the efficacy and safety of first-line PD-1/PD-L1 inhibitor in combination with CTLA-4 inhibitor (CP) in the treatment of patients with advanced NSCLC. A systemic search was conducted in four databases (PubMed, Cochrane library, Embase, and Web of Science) from their establishment until January 17, 2024, for randomized controlled trials that investigated the use of the first-line PD-1/PD-L1 inhibitor plus CTLA-4 inhibitor in patients with advanced NSCLC. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were subjected to meta-analyses. Totally 7 eligible randomized controlled trials including 4682 people were included. Two comparative analyses were performed: CP versus chemotherapy, CP versus PD-1/PD-L1 inhibitor (P). Compared with the chemotherapy group, CP improved OS (HR: 0.84, 95% CI: 0.75-0.94, p<0.05) but not PFS (HR: 0.94, 95%CI: 0.73-1.20, p = 0.63) or ORR (OR: 1.16, 95% CI: 0.79-1.71, p = 0.45). In terms of toxicity, CP had slightly fewer any AEs compared to chemotherapy (RR: 0.94, 95% CI: 0.91-0.97; p<0.05). Compared to the P group, there was no significant difference in OS (MD: -0,25, 95% CI: -2.47-1.98, p = 0.83), PFS (MD: -0.91, 95% CI: -3.19-1.36, p = 0.43), and ORR (OR:1.05, 95% CI. 0.80-1.36, p = 0.73). Subgroup analysis revealed that CP provided superior OS compared with P in patients with PD-L1 expression < 1%. CP was a feasible and safe first-line therapy for patients with advanced NSCLC. Specifically, CP may function as a therapeutic alternative for individuals with low or negative PD-L1 expression, resulting in enhanced long-term outcomes compared to chemotherapy or P. Further randomized controlled trials with prolonged follow-up periods are necessary to validate these results, particularly focusing on efficacy in patients with differing PD-L1 expression levels, to improve the stratified implementation of immunotherapy. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024621116, identifier CRD42024621116.
A metal affinity-immobilized magnetic liposome (MA-IML) was prepared in this research, which was with lipid and Ni 2+ content of 143.25 μ g/mg and 32 μ mol/mg, respectively. The antihypertensive peptides Ile-Pro-Pro (IPP) and Val-Pro-Pro (VPP) could be adsorbed onto MA-IML under specific conditions, and the adsorption kinetics was explored. The pseudo-second-order kinetics (R2value>0.98) was more suitable to describe the adsorption process of IPP and VPP than the intraparticle diffusion model and pseudo-first-order kinetic model. The results indicated that MA-IML could be used as an adsorbent for screening antihypertensive peptides from natural products.
Conventional clinical monotherapies for advanced hepatocellular carcinoma (HCC) have numerous limitations. Integrated oncology approaches can improve cancer treatment efficacy, and photothermal-chemotherapy drug delivery nanosystems (DDS) based on nanotechnology and biotechnology have piqued the interest of researchers. This study developed an aptamer-modified graphene quantum dots (GQDs)/magnetic chitosan DDS for photothermal-chemotherapy of HCC. The HCC aptamer and the EPR effect of nanoparticles, in particular, enable active and passive targeting of DDS to HCC. GQDs functioned as photosensitizers, effectively moderating photothermal therapy and inhibiting drug release during blood circulation. Magnetic chitosan demonstrated excellent drug encapsulation, acid sensitivity, and tumor imaging capabilities. Proper assembly of the units mentioned above enables precise combined therapy of HCC. This study indicates that DDS can significantly inhibit tumor growth while also extending the survival duration of tumor-bearing mice. The DDS (DOX-Fe3O4@CGA) shows strong synergistic tumor treatment potential, allowing for the exploration and development of novel HCC therapies.
Cytokines are the main regulators of innate and adaptive immunity, mediating communications between the cells of the immune system and regulating biological functions, including cell motility, differentiation, growth and apoptosis. Cytokines and cytokine receptors have been used in the treatment of tumors and autoimmune diseases, and to intervene in cytokine storms. Indeed, the use of monoclonal antibodies to block cytokine‑receptor interactions, as well as antibody‑cytokine fusion proteins has exhibited immense potential for the treatment of tumors and autoimmune diseases. Compared with these traditional types of antibodies, nanobodies not only maintain a high affinity and specificity, but also have the advantages of high thermal stability, a high capacity for chemical manipulation, low immunogenicity, good tissue permeability, rapid clearance and economic production. Thus, nanobodies have extensive potential for use in the diagnosis and treatment of cytokine‑related diseases. The present review summarizes the application of nanobodies in cytokine‑mediated immunotherapy and immunoimaging.
Cancer cells can develop in several ways to escape from death induced by chemotherapeutic agents, thereby weakening the anti-tumor efficacy of single-target chemotherapy. Therefore, the efficacy of conventional chemotherapy hits a single target in tumor cells subject to strict limits. In this article, an AS1411 aptamer-functionalized liposome is prepared, which can simultaneously deliver paclitaxel (PTX) and siRNA into MCF-7 cells in vitro and in vivo. The simultaneous delivery of PTX and siRNA synergistically increased the number of apoptotic cells and reduced angiogenesis. This delivery method exhibited significant advantages over combined delivery of PTX and siRNA separately by different liposomal drug delivery systems. Therefore, the simultaneous delivery of PTX and PLK1-targeted siRNA using AS1411 aptamer-functionalized liposome may have good potential clinical value for the therapy of breast cancer. Nanomedicine based on simultaneous delivery of chemotherapy drugs and siRNA gene provides an effective platform for improving tumor treatment methods.
278 Background: The most successful cancer chemotherapy regimens usually involve the administration of multiple cytotoxic agents simultaneously. Because different chemotherapies may have different mechanisms of action; it is difficult for cancer cells to become resistant to combination therapy. Recent investigations have discovered that nitric oxide (NO) may be involved in the reversal of cisplatin (CDDP) resistance in chemotherapy. Therefore, we sought to develop a combination regimen involving a NO-releasing prodrug (NO1) and cisplatin for the treatment of breast cancer. Methods: The prodrug NO1 was synthesized to be localized in tumor cells and to release nitric oxide over 10 hours. The antiproliferative activity of NO1 was determined in human breast cancer cell line, MDA-MB-468LN. To evaluate the effectiveness of the CDDP/NO combination regimen, platinum-resistant MDA-MB-468LN cells were treated with either cisplatin alone ([CDDP]=0.01, 0.02 or 0.03 mM) or the CDDP/NO combination ([CDDP]=0.01, 0.02 or 0.03 mM; [NO1]=0.02 mM). The cell viability was determined 48 hours post-treatment using a live/dead trypan blue exclusion assay. Results: The toxicity to breast cancer cells was higher than JS-K, a systemic NO agent currently in preclinical development. (NO1: IC 50 =26µM; JS-K: IC 50 =42 µM). In addition, NO1 had a long sustained release of nitric oxide, approximately one fold longer than JS-K (NO1: t1/2=6 h; JS-K: t1/2=3 h). The combination treatments resulted in 6.6-, 6.9- and 7.5-fold increase in cell death compared to cisplatin treatment alone at cisplatin concentrations of 0.01, 0.02 and 0.03 mM, respectively. A subsequent study in a murine xenograft of head and neck cancer found NO-1 conjugated to nanoparticles increased survival a mean of 10 weeks compared to controls (p<0.0001). Conclusions: Nitric oxide prodrug NO-1 and nanoparticles of it have high anticancer activity in vivo and they can reverse platinum resistance in vitro. Ongoing studies are examining the safety and efficacy of CDDP/NO combination therapy in mouse xenografts of human breast cancer.
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