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Shiraishi T Shirakusa T Miyoshi T Yamamoto S Hiratsuka M Iwasaki A Kawahara K 《The Thoracic and cardiovascular surgeon》2005,53(6):375-379
BACKGROUND: We report our 10-year experience of performing surgical resection of T4 lung cancer invading the thoracic aorta. PATIENTS AND METHODS: From 1994 to 2004, sixteen patients with T4 primary lung cancer with local invasion of the thoracic aorta underwent tumor resection. Surgical resection included 8 pneumonectomies and 8 lobectomies. The histologic type was squamous cell carcinoma in 7 patients, adenocarcinoma in 7, large cell carcinoma in 1, and small cell carcinoma in 1. Complete resection of the tumor with mediastinal lymph node dissection was achieved in 8 patients (50 %), while the resection was incomplete in the other 8 cases. RESULTS: The overall cumulative survival of the 16 patients at 3 and 5 years was 34.7 % and 17.4 %, respectively. The survival of the patients in the complete resection group was found to be 36.5 % at 5 years, with 2 patients surviving more than 5 years without a recurrence, which was significantly better than that of the incomplete resection group ( p = 0.005). CONCLUSIONS: Extended aortic resection with primary lung cancer is complex and possibly high risk, but can achieve long-term survival in selected patients. Surgical resection should be considered as a treatment option for T4 lung cancer for this T4 subcategory. 相似文献
104.
YongTae Kim Mark E. Lobatto Tomohiro Kawahara Bomy Lee Chung Aneta J. Mieszawska Brenda L. Sanchez-Gaytan Francois Fay Max L. Senders Claudia Calcagno Jacob Becraft May Tun Saung Ronald E. Gordon Erik S. G. Stroes Mingming Ma Omid C. Farokhzad Zahi A. Fayad Willem J. M. Mulder Robert Langer 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(3):1078-1083
Therapeutic and diagnostic nanomaterials are being intensely studied for several diseases, including cancer and atherosclerosis. However, the exact mechanism by which nanomedicines accumulate at targeted sites remains a topic of investigation, especially in the context of atherosclerotic disease. Models to accurately predict transvascular permeation of nanomedicines are needed to aid in design optimization. Here we show that an endothelialized microchip with controllable permeability can be used to probe nanoparticle translocation across an endothelial cell layer. To validate our in vitro model, we studied nanoparticle translocation in an in vivo rabbit model of atherosclerosis using a variety of preclinical and clinical imaging methods. Our results reveal that the translocation of lipid–polymer hybrid nanoparticles across the atherosclerotic endothelium is dependent on microvascular permeability. These results were mimicked with our microfluidic chip, demonstrating the potential utility of the model system.Improving the design of nanomedicines is key for their success and ultimate clinical application (1). The accumulation of such therapeutic or diagnostic nanomaterials primarily relies on enhanced endothelial permeability of the microvasculature in diseased tissue (2). This holds true for a wide range of pathological conditions, including inflammation, atherosclerosis, and most notably, oncological disease (3–6). Although attributed to the enhanced permeability and retention (EPR) effect, the exact mechanism by which nanoparticles accumulate in tumors continues to be a topic of research (7, 8). The “leaky” vasculature of tumors, which facilitates the extravasation of nanoparticles from microvessels (9), is a heterogeneous phenomenon that varies between different tumor models and even more so in patients. Moreover, the exploitation of nanomedicines in other conditions with enhanced microvessel permeability has only recently begun to be studied in detail. For example, in the last 5 y, a small but increasing number of preclinical studies that apply nanoparticle therapy in atherosclerosis models has surfaced (10). Although several targeting mechanisms have been proposed (4), the exact mechanism by which nanoparticles accumulate in atherosclerotic plaques remains to be investigated, but is likely facilitated by highly permeable neovessels that penetrate into the plaque from the vasa vasorum (Fig. 1A), a network of microvessels that supplies the wall of larger vessels (11).Open in a separate windowFig. 1.Development of an endothelialized microfluidic device to probe nanoparticle translocation over a permeable microvessel. (A) Schematics of continuous normal capillaries surrounding the vessel wall as well as permeable capillaries that penetrate into the atherosclerotic plaque from the vasa vasorum. (B) Schematic of an endothelialized microfluidic device that consists of two-layer microfluidic channels that are separated by a porous membrane (3 μm pore) on which ECs are grown. (C) TEER was dynamically measured across the endothelial layer on the membrane between the upper and lower channels. (D) A well-established monolayer of the microvascular endothelium is formed at TEER ∼400 (Ω·cm2). (E) The monolayer becomes highly permeable when stimulated with the inflammatory mediator, TNF-α, as well as with shear stress, with disruption of intercellular junctional structures (i.e., adherens junctions) between ECs, as evidenced by patchy expression of VE–cadherin (green) in the image on the right versus the left. Blue depicts nuclei stained with DAPI. (Scale bar, 20 μm.) (F) FITC–albumin translocation through the endothelial monolayer increases when the chip is treated with TNF-α. (G) The chip with endothelium cultured in different culture media [base, +FBS, +growth factors (GFs)] for 6 h shows a decrease in TEER with increased FITC–albumin translocation. No cell indicates the membrane only. TEER was normalized to the level with no cells (membrane only). (H) Schematic and TEM image of PEGylated lipid-coated nanoparticles encapsulating PLGA-conjugated AuNCs and Cy5.5. The average size was 69.7 ± 14 nm, which was measured from TEM images. (Scale bar, 100 nm.) Details on labeling, synthesis, characterization, and large-scale production procedures can be found in Materials and Methods and Fig. S2.Advances in biomedical imaging allow the study of plaque-targeting nanoparticles in a dynamic fashion with exceptional detail (12, 13). Microchip technology has the potential to monitor nanoparticle behavior at the (sub)cellular level. Microfluidic chips in which endothelial cells (ECs) are grown in the channels can serve as unique in vitro test systems to study microvascular function and associated disorders (14–18). They allow the isolation of specific biological hallmarks relevant to nanoparticle accumulation, such as the leaky endothelium. In the current study, we validate the potential utility of our microchip technology to study nanoparticle translocation over the endothelium and combine this with in vivo and ex vivo multimodality imaging studies on a rabbit model to better understand nanoparticle targeting of atherosclerotic plaques. 相似文献
105.
Regulation of activity of P2X7 receptor by its splice variants in cultured mouse astrocytes
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Yuuka Kido Chiyo Kawahara Yasuko Terai Akihiro Ohishi Satoshi Kobayashi Miki Hayakawa Yosuke Kamatsuka Kentaro Nishida Kazuki Nagasawa 《Glia》2014,62(3):440-451
Of purinergic receptors, P2X7 receptor (P2X7R, defined as a full‐length receptor) has unique characteristics, and its activation leads to ion channel activity and pore formation, causing cell death. Previously, we demonstrated that P2X7R expressed by nonstimulated astrocyte cultures obtained from SJL‐strain mice exhibits constitutive activation, implying its role in maintenance of cellular homeostasis. To obtain novel insights into its physiological roles, we examined whether constitutive activation of P2X7R is regulated by expression of its splice variants in such resting astrocytes, and whether their distinct expression profiles in different mouse strains affect activation levels of astrocytic P2X7Rs. In SJL‐ and ddY‐mouse astrocytes, spontaneous YO‐PRO‐1 uptake, an indicator of pore activity of P2X7R, was detected, but the uptake by the formers was significantly greater than that by the latter. Between the two mouse strains, there was a difference in their sensitivity of YO‐PRO‐1 uptake to antagonists, but not in the expression levels and sequences of P2X7R and pannexin‐1. Regarding expression of splice variants of P2X7R, expression of P2X7R variant‐3 (P2X7R‐v3) and ‐4 (P2X7R‐v4), but not variant‐2 and ‐k, was lower in SJL‐mouse astrocytes than in ddY‐mouse ones. On transfection of P2X7R‐v3 and ‐v4 into SJL‐mouse astrocytes, the pore activity was attenuated as in the case of the HEK293T cell‐expression system. These findings demonstrate that basal activity of P2X7R expressed by resting astrocytes is negatively regulated by P2X7R‐v3 and ‐v4, and that their distinct expression profiles result in the different activation levels of astrocytic P2X7Rs in different mouse strains. GLIA 2014;62:440–451 相似文献
106.
Shigeru Ono Kosaku Maeda Katsuhisa Baba Yoshiko Usui Yuki Tsuji Insu Kawahara Atsuhisa Fukuta Sachi Sekine 《Pediatric surgery international》2014,30(9):957-960
Neonates with congenital tracheal stenosis (CTS) sometimes develop respiratory distress and may be difficult to intubate. We used balloon tracheoplasty with a rigid bronchoscope for emergency airway management in neonates with symptomatic CTS. Herein, we describe the balloon tracheoplasty procedure and the early outcomes following its use as the initial treatment of neonatal symptomatic CTS. We performed a retrospective analysis of five neonates with CTS who were initially treated with balloon tracheoplasty at our institution from January 2010 to December 2013. Five patients with a mean birthweight of 2,117 g were treated during the study period. Of these, four developed respiratory distress after birth, and all patients had difficult intubations. In all five patients, definitive diagnosis of CTS was made by rigid bronchoscopy and 3-dimensional reconstruction scan. A total of nine balloon dilatations were performed in five patients. Following balloon tracheoplasty, two patients were extubated, one was extubated after resection and end-to-end anastomosis following initial balloon dilatation, and one remained hospitalized with tracheostomy for tracheomalacia. The remaining patient died from tracheal bleeding associated with congenital heart disease. Although our sample size was small, balloon tracheoplasty is a potentially effective initial treatment for selected cases with neonatal symptomatic CTS. 相似文献
107.
Noboru Inamura Akio Kubota Ryo Ishii Yoichiro Ishii Yukiko Kawazu Yuji Hamamichi Akihiro Yoneda Hisayuki Kawahara Hiroomi Okuyama Futoshi Kayatani 《Pediatric surgery international》2014,30(9):889-894
Object
The purpose of this study is to evaluate the outcome of our therapeutic strategy for antenatally diagnosed congenital diaphragmatic hernia (ADCDH).Methods
We treated 61 cases of ADCDH according to our strategy. Prostaglandin E1 was required to be maintained the patency of the ductus arteriosus (PDA) in 39 cases (Group I) while it was not administered in 22 cases (Group II). Left ventricular end-diastolic dimension (LVDD) and Tei index were measured with echocardiography on days 0, 2, and 7 after birth. Radical surgery was performed on all cases by day 2.Results
On day 0, Group I showed smaller LVDD and Tei index than those in Group II. Between day 0 and day 2, these parameters increased significantly in Group I, but not in Group II. On day 7, no significant difference in these parameters was observed between the two groups. Five patients died of cardiac and respiratory failure, resulting in a survival rate of 92 %.Conclusion
Our therapeutic strategy improves the clinical outcome of ADCDH. This can be attributed to two factors: earlier surgery resulting in improved LV function. The latter attenuates pulmonary hypertension and maintains PDA with a consequent decrease in right ventricular afterload to compensate for the low cardiac output resulting from PDA. 相似文献108.
109.
110.
Summary The renal handling of inorganic phosphate was studied by measuring the urinary excretion rate of phosphate (
), phosphate-(Cr51) EDTA clearance ratio (
) and maximal tubular reabsorption of phosphate per litre glomerular filtrate (
) during fasting in 26 ambulatory Type 1 (insulin-dependent) diabetic children without clinical signs of microangiopathy (age: 7–14 years; duration of disease: 3–14 years). Similar measurements were made in 28 healthy schoolchildren (age: 8–14 years).
and
were significantly enhanced in the diabetic children (p<0.001) and correlated with the degree of hyperglycaemia (p<0.005).
was significantly suppressed in the diabetic children (1.23 versus 1.73 mmol/1, p<0.001). This disturbance was neither related to changes in serum parathyroid hormone nor to growth hormone concentrations but was inversely correlated with the degree of hyperglycaemia (r=-0.61, p<0.001) and with tubular reabsorption of glucose in the diabetic subjects, the mean maximal (
) and absolute tubular phosphate reabsorption rates were equal to those of the 28 healthy subjects. Both in the diabetic and healthy subjects, these parameters were positively correlated with glomerular filtration rate which was significantly elevated in the diabetic children (138 versus 109 ml/min per 1.73 m2, p<0.01). The study demonstrates a dysfunction in tubular phosphate reabsorption in diabetic children which is related to glycaemic regulation. 相似文献