No abstract

Background: No definitive comparisons of surgical morbidity between segmentectomy and lobectomy for non-small cell lung cancer have been reported.Methods: We conducted a randomized controlled trial to confirm the noninferiority of segmentectomy to lobectomy in regard to prognosis (trial No. JCOG0802/ WJOG4607L). Patients with invasive peripheral non-small cell lung cancer tumor of a diameter 2 cm were randomized to undergo either lobectomy or segmentectomy. The primary end point was overall survival. Here, we have focused on morbidity and mortality. Predictors of surgical morbidity were evaluated by the mode of surgery. Segmentectomy was categorized into simple and complex. Simple segmentectomy was defined as segmental resection of the right or left segment 6, left superior, or lingular segment. Complex segmentectomy was resection of the other segment. This trial is registered with the University Hospital Medical Information Network-Clinical Trial Registry (UMIN000002317).

SummaryDefects in articular cartilage ultimately result in loss of joint function. Repairing cartilage defects requires cell sources. We developed an approach to generate scaffoldless hyaline cartilage from human induced pluripotent stem cells (hiPSCs). We initially generated an hiPSC line that specifically expressed GFP in cartilage when teratoma was formed. We optimized the culture conditions and found BMP2, transforming growth factor β1 (TGF-β1), and GDF5 critical for GFP expression and thus chondrogenic differentiation of the hiPSCs. The subsequent use of scaffoldless suspension culture contributed to purification, producing homogenous cartilaginous particles. Subcutaneous transplantation of the hiPSC-derived particles generated hyaline cartilage that expressed type II collagen, but not type I collagen, in immunodeficiency mice. Transplantation of the particles into joint surface defects in immunodeficiency rats and immunosuppressed mini-pigs indicated that neocartilage survived and had potential for integration into native cartilage. The immunodeficiency mice and rats suffered from neither tumors nor ectopic tissue formation. The hiPSC-derived cartilaginous particles constitute a viable cell source for regenerating cartilage defects.

Human microvascular pericytes (CD146+/34−/45−/56−) contain multipotent precursors and repair/regenerate defective tissues, notably skeletal muscle. However, their ability to repair the ischemic heart remains unknown. We investigated the therapeutic potential of human pericytes, purified from skeletal muscle, for treating ischemic heart disease and mediating associated repair mechanisms in mice. Echocardiography revealed that pericyte transplantation attenuated left ventricular dilatation and significantly improved cardiac contractility, superior to CD56+ myogenic progenitor transplantation, in acutely infarcted mouse hearts. Pericyte treatment substantially reduced myocardial fibrosis and significantly diminished infiltration of host inflammatory cells at the infarct site. Hypoxic pericyte-conditioned medium suppressed murine fibroblast proliferation and inhibited macrophage proliferation in vitro. High expression by pericytes of immunoregulatory molecules, including IL-6, LIF, COX-2 and HMOX-1, was sustained under hypoxia, except for MCP-1. Host angiogenesis was significantly increased. Pericytes supported microvascular structures in vivo and formed capillary-like networks with/without endothelial cells in three-dimensional co-cultures. Under hypoxia, pericytes dramatically increased expression of VEGF-A, PDGF-β, TGF-β1 and corresponding receptors while expression of bFGF, HGF, EGF, and Ang-1 was repressed. The capacity of pericytes to differentiate into and/or fuse with cardiac cells was revealed by GFP-labeling, though to a minor extent. In conclusion, intramyocardial transplantation of purified human pericytes promotes functional and structural recovery, attributable to multiple mechanisms involving paracrine effects and cellular interactions.

Gain-of-function mutations in the fibroblast growth factor receptor 3 gene (FGFR3) result in skeletal dysplasias, such as thanatophoric dysplasia and achondroplasia (ACH). The lack of disease models using human cells has hampered the identification of a clinically effective treatment for these diseases. Here we show that statin treatment can rescue patient-specific induced pluripotent stem cell (iPSC) models and a mouse model of FGFR3 skeletal dysplasia. We converted fibroblasts from thanatophoric dysplasia type I (TD1) and ACH patients into iPSCs. The chondrogenic differentiation of TD1 iPSCs and ACH iPSCs resulted in the formation of degraded cartilage. We found that statins could correct the degraded cartilage in both chondrogenically differentiated TD1 and ACH iPSCs. Treatment of ACH model mice with statin led to a significant recovery of bone growth. These results suggest that statins could represent a medical treatment for infants and children with TD1 and ACH.

Purpose: Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy with poor prognosis. Patients with MPM who do not respond to standard firstline chemotherapy have limited treatment options. We evaluated the efficacy and safety of nivolumab, an immune checkpoint inhibitor, for the treatment of advanced or metastatic MPM. Patients and Methods: Japanese patients with unresectable, advanced, or metastatic MPM resistant or intolerant to 2 regimens of chemotherapy and 1 measurable lesion (s) were enrolled. Patients received nivolumab 240 mg intravenously every 2 weeks until progressive disease or unacceptable toxicity. The primary endpoint was objective response rate by central assessment according to the Modified Response Evaluation Criteria in Solid Tumors. Adverse events (AEs) and treatment-related AEs (TRAEs) were evaluated. Results: Thirty-four patients were enrolled between July 2016 and October 2016. Median follow-up was 16.8 (range: 1.8-20.2) months. Ten (29%, 95% confidence interval, 16.8-46.2) patients showed a centrally assessed objective response. The objective response rates were 26% (7/27), 67% (2/3), and 25% (1/4) patients for epithelioid, sarcomatoid, and biphasic histologic subtypes, respectively. Median duration of response was 11.1 months with a 68% disease control rate. Median overall survival and progression-free survival were 17.3 and 6.1 months, respectively. The objective response rate was 40% with programmed death-ligand 1 expression 1% and 8% with <1%. Thirty-two patients (94%) experienced AEs and 26 (76%) experienced TRAEs. Conclusions: Nivolumab met the primary endpoint as second-or third-line treatment for patients with MPM and showed promising efficacy with manageable toxicity. See related commentary by Mansfield and Zauderer, p. 5438

Our findings suggest that VEGF is essential for the induction of angiogenesis and functional improvements observed after MDSC transplantation for infarct repair.

A new method for the extraction of the active coagulation component from Moringa oleifera seeds was developed and compared with the ordinary water extraction method (MOC-DW). In the new method, 1.0 mol l-1 solution of sodium chloride (MOC-SC) and other salts were used for extraction of the active coagulation component. Batch coagulation experiments were conducted using 500 ml of low turbid water (50 NTU). Coagulation efficiencies were evaluated based on the dosage required to remove kaolinite turbidity in water. MOC-SC showed better coagulation activity with dosages 7.4 times lower than that using MOC-DW for the removal of kaolinite turbidity. MOC-SC could effectively coagulate more than 95% of the 50 NTU initial kaolin turbidity using only 4 ml l-1 , while 32 ml l-1 of MOC-DW could only remove about 78% of the same kaolin turbidity. The improvement of coagulation efficiency by NaCl is apparently due to the salting-in mechanism in proteins wherein a salt increases protein-protein dissociations leading to increasing protein solubility as the salt ionic strength increases. There was no difference in the coagulation efficiency observed for extracts using any of four 1:1 salts (NaCl, KNO3, KCl and NaNO3) in our study. Purification and isolation of the active component confirmed that the active component of MOC-SC was mainly protein.