Experimental Assessment of Restoration of the Bronchial Artery in Sleeve Lobectomy Combined with Pulmonary Angioplasty

The restoration of the bronchial artery after bronchoplasty combined with pulmonary angioplasty was studied in relation to the degree of stenosis of the pulmonary artery by means of the microangiographic technique. Thirty-three dogs were used in this study. They were divided into Group A (15 dogs) with sleeve lobectomy alone, Group B (10 dogs) with sleeve lobectomy and a 50% stenosis of the left main pulmonary artery and Group C (8 dogs) with sleeve lobectomy and a 75% stenosis of the left main pulmonary artery. The restoration of the bronchial artery was assessed by microangiography. 1) The restoration of th bronchial artery after bronchoplasty was completed on day 14. The trend toward a ready regeneration of the bronchial artery becomes apparent if some degree of stenosis of the pulmonary artery exists after a duration of seven days. 2) The interrupted bronchial artery starts to restore at the adventitial face and extends throughout the whole wall of the bronchus after the 7th day. 3) From these results, an operative procedure of sleeve lobectomy with pulmonary angioplasty is applicable even though stenosis of the pulmonary artery remains to some degree

Reduction of lung metastasis, cell invasion, and adhesion in mouse melanoma by statin-induced blockade of the Rho/Rho-associated coiled-coil-containing protein kinase pathway

<p>Abstract</p> <p>Background</p> <p>Melanomas are highly malignant and have high metastatic potential; hence, there is a need for new therapeutic strategies to prevent cell metastasis. In the present study, we investigated whether statins inhibit tumor cell migration, invasion, adhesion, and metastasis in the B16BL6 mouse melanoma cell line.</p> <p>Methods</p> <p>The cytotoxicity of statins toward the B16BL6 cells were evaluated using a cell viability assay. As an experimental model, B16BL6 cells were intravenously injected into C57BL/6 mice. Cell migration and invasion were assessed using Boyden chamber assays. Cell adhesion analysis was performed using type I collagen-, type IV collagen-, fibronectin-, and laminin-coated plates. The mRNA levels, enzyme activities and protein levels of matrix metalloproteinases (MMPs) were determined using RT-PCR, activity assay kits, and Western blot analysis, respectively; the mRNA and protein levels of vary late antigens (VLAs) were also determined. The effects of statins on signal transduction molecules were determined by western blot analyses.</p> <p>Results</p> <p>We found that statins significantly inhibited lung metastasis, cell migration, invasion, and adhesion at concentrations that did not have cytotoxic effects on B16BL6 cells. Statins also inhibited the mRNA expressions and enzymatic activities of matrix metalloproteinases (MMPs). Moreover, they suppressed the mRNA and protein expressions of integrin α₂, integrin α₄, and integrin α₅and decreased the membrane localization of Rho, and phosphorylated LIM kinase (LIMK) and myosin light chain (MLC).</p> <p>Conclusions</p> <p>The results indicated that statins suppressed the Rho/Rho-associated coiled-coil-containing protein kinase (ROCK) pathways, thereby inhibiting B16BL6 cell migration, invasion, adhesion, and metastasis. Furthermore, they markedly inhibited clinically evident metastasis. Thus, these findings suggest that statins have potential clinical applications for the treatment of tumor cell metastasis.</p

High Serum Advanced Glycation End Products Are Associated with Decreased Insulin Secretion in Patients with Type 2 Diabetes: A Brief Report

Advanced glycation end products (AGEs) are important in the pathophysiology of type 2 diabetes mellitus (T2DM). They directly cause insulin secretory defects in animal and cell culture models and may promote insulin resistance in nondiabetic subjects. We have developed a highly sensitive liquid chromatography-tandem mass spectrometry method for measuring AGEs in human serum. Here, we use this method to investigate the relationship between AGEs and insulin secretion and resistance in patients with T2DM. Methods. Our study involved 15 participants with T2DM not on medication and 20 nondiabetic healthy participants. We measured the AGE carboxyethyllysine (CEL), carboxymethyllysine (CML), and methyl-glyoxal-hydro-imidazolone (MG-H1). Plasma glucose and insulin were measured in these participants during a meal tolerance test, and the glucose disposal rate was measured during a euglycemic-hyperinsulinemic clamp. Results. CML and CEL levels were significantly higher in T2DM than non-DM participants. CML showed a significant negative correlation with insulin secretion, HOMA-%B, and a significant positive correlation with the insulin sensitivity index in T2DM participants. There was no correlation between any of the AGEs measured and glucose disposal rate. Conclusions. These results suggest that AGE might play a role in the development or prediction of insulin secretory defects in type 2 diabetes

Surgical Treatment for Pulmonary Metastases

This study is based on 29 patients undergoing resection for pulmonary metastases from 1960 to 1981 in our clinics. Factors concerning their prognosis are discussed in this study. 1) Prognosis following surgery is associated with the origin of the primary disease, the sizes and numbers of pulmonary metastases, and the disease-free period. 2) Pulmonary metastases arising from original tumors with slow growth rate, such as thyroid cancer, breast cancer, and some of osteogenic sarcomas, are favorable candidates for surgical treatment. 3) Operative methods of choice are not essential in anticipating better results. Complete removal of the tumor is required. We assume that improved chemotherapy may be contributary to a gain in a longer survival

Results of the first sea-test of Tsukuyomi: A prototype of underwater gliders for virtual mooring

This paper presents the results of the first sea-test of Tsukuyomi - a prototype of underwater gliders for virtual mooring. Its will be able to stay in a designated water for more than one year, reciprocating between the sea-surface and the seafloor up to 3,000 meters in depth. It will sleep on the seafloor to elongate the operation time. We have successfully conducted tank-test in December 2011 and the first sea-test in March 2012. Although for the sake of safety, a thin string was connected to Tsukuyomi in the first sea-test, the dynamic stability, the maneuverability and the basic function of Tsukuyomi were confirmed.Date of Conference: 14-19 October 2012http://www.godac.jamstec.go.jp/darwin/cruise/kaiyo/ky12-04/

TIGIT/CD155 axis mediates resistance to immunotherapy in patients with melanoma with the inflamed tumor microenvironment

Background Patients with cancer benefit from treatment with immune checkpoint inhibitors (ICIs), and those with an inflamed tumor microenvironment (TME) and/or high tumor mutation burden (TMB), particularly, tend to respond to ICIs; however, some patients fail, whereas others acquire resistance after initial response despite the inflamed TME and/or high TMB. We assessed the detailed biological mechanisms of resistance to ICIs such as programmed death 1 and/or cytotoxic T-lymphocyte-associated protein 4 blockade therapies using clinical samples. Methods We established four pairs of autologous tumor cell lines and tumor-infiltrating lymphocytes (TILs) from patients with melanoma treated with ICIs. These tumor cell lines and TILs were subjected to comprehensive analyses and in vitro functional assays. We assessed tumor volume and TILs in vivo mouse models to validate identified mechanism. Furthermore, we analyzed additional clinical samples from another large melanoma cohort. Results Two patients were super-responders, and the others acquired resistance: the first patient had a non-inflamed TME and acquired resistance due to the loss of the beta-2 microglobulin gene, and the other acquired resistance despite having inflamed TME and extremely high TMB which are reportedly predictive biomarkers. Tumor cell line and paired TIL analyses showed high CD155, TIGIT ligand, and TIGIT expression in the tumor cell line and tumor-infiltrating T cells, respectively. TIGIT blockade or CD155-deletion activated T cells in a functional assay using an autologous cell line and paired TILs from this patient. CD155 expression increased in surviving tumor cells after coculturing with TILs from a responder, which suppressed TIGIT+ T-cell activation. Consistently, TIGIT blockade or CD155-deletion could aid in overcoming resistance to ICIs in vivo mouse models. In clinical samples, CD155 was related to resistance to ICIs in patients with melanoma with an inflamed TME, including both primary and acquired resistance. Conclusions The TIGIT/CD155 axis mediates resistance to ICIs in patients with melanoma with an inflamed TME, promoting the development of TIGIT blockade therapies in such patients with cancer