Purpose:
We assessed the efficacy and safety of camrelizumab [an anti-programmed death (PD-1) mAb] plus apatinib (a VEGFR-2 tyrosine kinase inhibitor) in patients with advanced hepatocellular carcinoma (HCC).
Patients and Methods:
This nonrandomized, open-label, multicenter, phase II study enrolled patients with advanced HCC who were treatment-naïve or refractory/intolerant to first-line targeted therapy. Patients received intravenous camrelizumab 200 mg (for bodyweight ≥50 kg) or 3 mg/kg (for bodyweight <50 kg) every 2 weeks plus oral apatinib 250 mg daily. The primary endpoint was objective response rate (ORR) assessed by an independent review committee (IRC) per RECIST v1.1.
Results:
Seventy patients in the first-line setting and 120 patients in the second-line setting were enrolled. As of January 10, 2020, the ORR was 34.3% [24/70; 95% confidence interval (CI), 23.3–46.6] in the first-line and 22.5% (27/120; 95% CI, 15.4–31.0) in the second-line cohort per IRC. Median progression-free survival in both cohorts was 5.7 months (95% CI, 5.4–7.4) and 5.5 months (95% CI, 3.7–5.6), respectively. The 12-month survival rate was 74.7% (95% CI, 62.5–83.5) and 68.2% (95% CI, 59.0–75.7), respectively. Grade ≥3 treatment-related adverse events (TRAE) were reported in 147 (77.4%) of 190 patients, with the most common being hypertension (34.2%). Serious TRAEs occurred in 55 (28.9%) patients. Two (1.1%) treatment-related deaths occurred.
Conclusions:
Camrelizumab combined with apatinib showed promising efficacy and manageable safety in patients with advanced HCC in both the first-line and second-line setting. It might represent a novel treatment option for these patients.
See related commentary by Pinato et al., p. 908
marrow-derived mesenchymal stem cell attenuates skin fibrosis development in mice. Int Wound J 2014; 11:701-710 Abstract Recent studies showed that mesenchymal stem cell (MSC) transplantation significantly alleviated tissue fibrosis; however, little is known about the efficacy on attenuating cutaneous scar formation. In this study, we established a dermal fibrosis model induced by bleomycin and evaluated the benefit of bone marrow-derived mesenchymal stem cells (BM-MSCs) on skin fibrosis development. Tracing assay of green fluorescent protein (GFP + )BM-MSCs showed that the cells disappeared gradually within 24 hours upon administration, which hinted the action of BM-MSCs in vivo was exerted in the initial phase of repair in this model. Therefore, we repeatedly transplanted syngeneic BM-MSCs in the process of skin fibrosis formation. After 3 weeks, it was found that BM-MSC-treated lesional skin demonstrated a unanimous basket-weave organisation of collagen arrangement similar to normal skin, with few inflammatory cells. In addition, lesional skin with BM-MSC treatment exhibited a significant down-regulation of transforming growth factor-β1 (TGF-β1), type I collagen and heat-shock protein 47 (HSP47), with higher expression of matrix metalloproteinases (MMPs)-2, -9 and -13. Further experiments showed that α-smooth muscle actin (α-SMA) positive cells, the most reliable marker of myofibroblasts, apparently decreased after BM-MSC transplantation, which revealed that BM-MSCs could attenuate myofibroblast proliferation and differentiation as well as matrix production. Taken together, these findings suggested that BM-MSCs can inhibit the formation process of bleomycin-induced skin fibrosis, alleviate inflammation and favour the remodelling of extracellular matrix.
Ischemic diseases, which are caused by a reduction of blood supply that results in reduced oxygen transfer and nutrient uptake, are becoming the leading cause of disabilities and deaths. Therapeutic angiogenesis is key for the treatment of these diseases. Stem cells have been used in animal models and clinical trials to treat various ischemic diseases. Recently, the efficacy of stem cell therapy has increasingly been attributed to exocrine functions, particularly extracellular vesicles. Extracellular vesicles are thought to act as intercellular communication vehicles to transport informational molecules including proteins, mRNA, microRNAs, DNA fragments, and lipids. Studies have demonstrated that extracellular vesicles promote angiogenesis in cellular experiments and animal models. Herein, recent reports on the use of extracellular vesicles for therapeutic angiogenesis during ischemic diseases are presented and discussed. We believe that extracellular vesicles-based therapeutics will be an ideal treatment method for patients with ischemic diseases.
Acute full-thickness skin wounds (FTSW) caused by extensive burns or high-energy trauma are not adequately addressed by current clinical treatments. This study hypothesized that biomimetic nanofiber scaffolds (NFSs) functionalized with rich attachment of bone-marrow-derived mesenchymal stem cells (BM-MSCs) can promote wound healing in acute FTSW. Results in a rat model showed that both NFS and BM-MSCs contributed to the wound healing. Wounds in NFS group with a higher density of BM-MSCs achieved complete closure 8 days earlier than the control group. Implanted BM-MSCs were found to promote epithelial edge ingrowth and collagen synthesis. The colocation of BM-MSCs (tagged with quantum-dots) with the expression of keratin 10 and filaggrin indicated the participation of BM-MSCs in epidermal differentiation at early and intermediate stages under the local wounding environment. Overall, this study suggests a great potential of using NFS/BM-MSC composites for the treatment of acute FTSW.
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