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Toshio Onitsuka

Bio: Toshio Onitsuka is an academic researcher from Yokohama National University. The author has contributed to research in topics: Lung cancer & Aneurysm. The author has an hindex of 22, co-authored 130 publications receiving 1761 citations.


Papers
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Journal ArticleDOI
TL;DR: In this article, the authors carried out histological study of abdominal aortic aneurysm (AAA) tissues of patients, and interventional animal and cell culture experiments to investigate a role of mast cells in the pathogenesis of AAA.
Abstract: Abdominal aortic aneurysm (AAA) is histologically characterized by medial degeneration and various degrees of chronic adventitial inflammation, although the mechanisms for progression of aneurysm are poorly understood. In the present study, we carried out histological study of AAA tissues of patients, and interventional animal and cell culture experiments to investigate a role of mast cells in the pathogenesis of AAA. The number of mast cells was found to increase in the outer media or adventitia of human AAA, showing a positive correlation between the cell number and the AAA diameter. Aneurysmal dilatation of the aorta was seen in the control (+/+) rats following periaortic application of calcium chloride (CaCl2) treatment but not in the mast cell–deficient mutant Ws/Ws rats. The AAA formation was accompanied by accumulation of mast cells, T lymphocytes and by activated matrix metalloproteinase 9, reduced elastin levels and augmented angiogenesis in the aortic tissue, but these changes were much less in the Ws/Ws rats than in the controls. Similarly, mast cells were accumulated and activated at the adventitia of aneurysmal aorta in the apolipoprotein E–deficient mice. The pharmacological intervention with the tranilast, an inhibitor of mast cell degranulation, attenuated AAA development in these rodent models. In the cell culture experiment, a mast cell directly augmented matrix metalloproteinase 9 activity produced by the monocyte/macrophage. Collectively, these data suggest that adventitial mast cells play a critical role in the progression of AAA.

151 citations

Journal Article
TL;DR: A high preoperative NLR may be a convenient biomarker to identify patients with a poor prognosis after resection for NSCLC and was an independent risk factor for reduced survival.
Abstract: Background: The prognostic impact of neutrophil to lymphocyte ratio (NLR) in non-small cell lung cancer (NSCLC) was examined using patients with a follow-up period more than 5 years. Patients and Methods: Two hundred and eighty four consecutive resected NSCLC patients were reviewed retrospectively. In this study, patients who were treated with a follow-up period less than 5 years were omitted, Results: The mean value of NLR was 2.44±2.22 (range: 0.56-29.44). The 5-year survival of the patients with a high NLR (≥2.5) was significantly worse than that of the patients with a low NLR (47.06% vs. 67.84%, p<0.0001). Univariate analysis of the clinicopathological factors affecting survival revealed that age, gender, histology, pT status, pN status, high serum CEA level, positive findings of pleural lavage cytology and high NLR were significant risk factors for reduced survival. On multivariate analysis, a high NLR was an independent risk factor for reduced survival. Conclusion: A high preoperative NLR may be a convenient biomarker to identify patients with a poor prognosis after resection for NSCLC. It is generally agreed that inflammatory cells in the tumour microenvironment have significant effects on tumour development (1,2). The neutrophil count or neutrophil to lymphocyte ratio (NLR) has been documented as a simple index of systemic inflammatory response in critically ill patients with malignancy (3-14). These previous studies except for one (14) also showed that a high pretreatment NLR was associated with poor survival in patients with various malignancies (3-13). The European Lung Cancer Working Group (15) and The Japan Multinational Trial Organisation (16) found that the high neutrophil count was an independent prognostic factor for poor survival in patients with non-small cell lung cancer (NSCLC). Tibaldi et al. (17) also reported similar results. Unfortunately their results were not applicable to surgical patients because patients examined in these studies were unresectable advanced NSCLC (Stage IIIB and IV). Ferrigno et al. (18) also found that the neutrophil count was of prognostic value in newly diagnosed patients with lung cancer, however they included 771/1201 (64.2%) patients with distant metastasis and 134/1201 (11.1%) patients with small cell lung cancer. To our knowledge, only one study has examined the prognostic significance of NLR for patients with completely resected NSCLC (19) and reported that an increasing preoperative NLR was associated with higher stage, but remained an independent predictor of survival after complete resection. However, this study included relatively many patients with Stage III and IV disease (27.68%) and only 14% of Stage IA disease. Furthermore, the cumulative survival rate was occasionally confounded due patients with short follow-up period. In the present study, the prognostic impact of the NLR was retrospectively investigated for completely resected NSCLC patients with a follow-up period more than 5 years.

140 citations

Journal ArticleDOI
TL;DR: There appears to be a direct correlation between the number of mast cells and tumor angiogenesis in patients with lung cancer, and this relationship seems to be independent of vascular endothelial growth factor expression.

115 citations

Journal Article
TL;DR: The preoperative serum CRP level is an independent and significant indicator predictive of a poor prognosis in patients with NSCLC.
Abstract: We evaluated the significance of the preoperative serum C-reactive protein (CRP) level as a prognostic indicator in patients with non-small cell lung cancer (NSCLC) Patients and Methods: Two hundred and three patients who had undergone a curative resection of NSCLC were retrospectively reviewed Results: The proportion of the tumor size over 3 cm per patient in the CRP-positive group (≥05 mg/dL: n=38) was significantly higher than that in the CRP-negative group (<05 mg/dL: n=165) The proportion of the adenocarcinoma in CRP-positive group was significantly lower than that in CRP-negative group The overall and disease specific survival rates in the CRP-positive group were significantly lower than the rates in the CRP-negative group Based on a multivariate analysis, the preoperative serum CRP level was selected as one of the unfavorable indicators regarding survival Conclusion: The preoperative serum CRP level is an independent and significant indicator predictive of a poor prognosis in patients with NSCLC C-reactive protein (CRP) is an acute-phase reactant The preoperative serum elevation of CRP has been identified to be a significant prognostic factor in patients with colorectal (1, 2), esophageal (3, 4), hepatic (5), and pancreas cancer (6) The plasma CRP level has been shown to be associated with non-small cell carcinoma (NSCLC) (7) and the prognosis of advanced NSCLC (8) However, no previous study has ever described a relationship between the preoperative peripheral CRP level and the prognosis in NSCLC patients who underwent a curative operation The aim of this study was to investigate the significance of CRP in the long-term prognosis in a NSCLC patient population who had all undergone a curative operation Patients and Methods Two hundred and three patients who had undergone a curative resection of NSCLC between January 1998 and December 2003 were enrolled in this study Curative operations were defined those of the patients with no residual macroscopic disease after surgery Blood samples were obtained prior to the surgery The serum levels of CRP were measured by a latex photometric immunoassay (Mitsubishi Kagaku Iatron, Tokyo, Japan) Patients with serum CRP levels <05 mg/dL were assigned to the CRP-negative group, whereas patients with serum CRP levels ≥05 mg/dL were assigned to the CRP-positive group according to the manufacturer's instructions We also measured the serum levels of lactate dehydrogenase (LDH) (normal limits, 119-229 U/L) and white blood cell (WBC) count (5000-9000/mm 3 ) The Mann-Whitney U-test was used for the statistical analysis The categorical data were compared using the ¯ 2 test Survival was evaluated by the Kaplan-Meier method, and differences among the survival curves were tested using the log-rank test Multivariate analyses according to the Cox's proportional hazards model was used to assess the overall and disease-specific survivals as well as the influence of the clinical parameters Statistical calculations were conducted with JMP (SAS Institute Inc Cary, NC, USA) and values of p less than 005 were accepted as significant

92 citations

Journal Article
TL;DR: Univariate and multivariate analyses of the clinicopathological factors affecting survival revealed that the combined use of preoperative NLR and CRP was an independent prognostic determinant.
Abstract: Background: Previous studies showed the prognostic impact of inflammatory markers such as the neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP), in resected non-small cell lung cancer (NSCLC). However, there are no studies that examined both of these markers simultaneously. Patients and Methods: Three hundred and one consecutive cases of resected NSCLC with a follow-up period of more than 5 years were reviewed retrospectively. Results: A significant association was only observed between NLR and patients' survival (p<0.0001). High CRP also led to a higher 5-year survival rate than low CRP (38.71% vs. 70.71%, p<0.0001). We evaluated the prognostic significance of the use of NLR and CRP combined. The 5-year survival of patients with both low NLR and low CRP was 74.18%. On the other hand, that of patients with both of these at a low level was significantly poor (20.00%, p<0.0001). Univariate and multivariate analyses of the clinicopathological factors affecting survival revealed that the combined use of preoperative NLR and CRP was an independent prognostic determinant. Conclusion: The combined use of preoperative NLR and CRP might be useful to predict the prognosis of patients with NSCLC.

85 citations


Cited by
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TL;DR: A high NLR is associated with an adverse OS in many solid tumors, and its addition to established prognostic scores for clinical decision making warrants further investigation.
Abstract: BACKGROUND: Inflammation may play an important role in cancer progression, and a high neutrophil-to-lymphocyte ratio (NLR) has been reported to be a poor prognostic indicator in several malignancies. Here we quantify the prognostic impact of this biomarker and assess its consistency in solid tumors. METHODS: A systematic review of electronic databases was conducted to identify publications exploring the association of blood NLR and clinical outcome in solid tumors. Overall survival (OS) was the primary outcome, and cancer-specific survival (CSS), progression-free survival (PFS), and disease-free survival (DFS) were secondary outcomes. Data from studies reporting a hazard ratio and 95% confidence interval (CI) or a P value were pooled in a meta-analysis. Pooled hazard ratios were computed and weighted using generic inverse-variance and random-effect modeling. All statistical tests were two-sided. RESULTS: One hundred studies comprising 40559 patients were included in the analysis, 57 of them published in 2012 or later. Median cutoff for NLR was 4. Overall, NLR greater than the cutoff was associated with a hazard ratio for OS of 1.81 (95% CI = 1.67 to 1.97; P < .001), an effect observed in all disease subgroups, sites, and stages. Hazard ratios for NLR greater than the cutoff for CSS, PFS, and DFS were 1.61, 1.63, and 2.27, respectively (all P < .001). CONCLUSIONS: A high NLR is associated with an adverse OS in many solid tumors. The NLR is a readily available and inexpensive biomarker, and its addition to established prognostic scores for clinical decision making warrants further investigation.

2,143 citations

Book
20 Sep 2004
TL;DR: This book will not become a unity of the way for you to get amazing benefits at all, but, it will serve something that will let you get the best time and moment to spend for reading the book.
Abstract: It sounds good when knowing the pathology and genetics of tumours of the lung pleura thymus and heart in this website. This is one of the books that many people looking for. In the past, many people ask about this book as their favourite book to read and collect. And now, we present hat you need quickly. It seems to be so happy to offer you this famous book. It will not become a unity of the way for you to get amazing benefits at all. But, it will serve something that will let you get the best time and moment to spend for reading the book.

1,858 citations

Journal ArticleDOI
TL;DR: The present systematic review examines and comments on the clinical utility of the neutrophil-lymphocyte ratio, which has shown that NLR is elevated in patients with more advanced or aggressive disease evidenced by increased tumour stage, nodal stage, number of metastatic lesions and as such these patients may represent a particularly high-risk patient population.
Abstract: There is increasing and consistent evidence that cancer-associated inflammation is a key determinant of outcome in patients with cancer. Various markers of inflammation have been examined over the past decade in an attempt to refine stratification of patients to treatment and predict survival. One routinely available marker of the systemic inflammatory response is the neutrophil-lymphocyte ratio (NLR), which is derived from the absolute neutrophil and absolute lymphocyte counts of a full blood count. To date, over 60 studies (>37,000 patients) have examined the clinical utility of the NLR to predict patient outcomes in a variety of cancers. The present systematic review examines and comments on the clinical utility of the NLR. The NLR had independent prognostic value in (a) unselected cohorts (1 study of >12,000 patients), (b) operable disease (20 studies, >4000 patients), (c) patients receiving neoadjuvant treatment and resection (5 studies, >1000 patients), (d) patients receiving chemo/radiotherapy (12 studies, >2000 patients) and (e) patients with inoperable disease (6 studies, >1200 patients). These studies originated from ten different countries, in particular UK, Japan, and China. Further, correlative studies (15 studies, >8500 patients) have shown that NLR is elevated in patients with more advanced or aggressive disease evidenced by increased tumour stage, nodal stage, number of metastatic lesions and as such these patients may represent a particularly high-risk patient population. Further studies investigating the tumour and host-derived factors regulating the systemic inflammatory response, in particular the NLR, may identify novel treatment strategies for patients with cancer.

1,111 citations

Journal ArticleDOI
TL;DR: This review highlights the aspects of cancer development that, like organogenesis during embryonic development and tissue repair in adult mammals, are regulated by interactions between epithelial cells, activated stromal cells, and soluble and insoluble components of the extracellular matrix.
Abstract: In the past 25 years, a majority of cancer studies have focused on examining functional consequences of activating and/or inactivating mutations in critical genes implicated in cell cycle control. These studies have taught us a great deal about the functions of oncogenes and tumor suppressor genes and the signaling pathways regulating cell proliferation and/or cell death. However, such studies have largely ignored the fact that cancers are heterogeneous cellular entities whose growth is dependent upon reciprocal interactions between genetically altered “initiated” cells and the dynamic microenvironment in which they live. This review highlights the aspects of cancer development that, like organogenesis during embryonic development and tissue repair in adult mammals, are regulated by interactions between epithelial cells, activated stromal cells, and soluble and insoluble components of the extracellular matrix.

952 citations

Journal ArticleDOI
TL;DR: Good evidence is demonstrated that there is now good evidence that preoperative measures of the systemic inflammatory response predict cancer survival, independent of tumor stage, in primary operable cancer.
Abstract: Disease progression in cancer is dependent on the complex interaction between the tumor and the host inflammatory response. There is substantial evidence in advanced cancer that host factors, such as weight loss, poor performance status and the host systemic inflammatory response, are linked, and the latter is an important tumor-stage-independent predictor of outcome. Indeed, the systemic inflammatory response, as evidenced by an elevated level of C-reactive protein, is now included in the definition of cancer cachexia. This review examines the role of the systemic inflammatory response in predicting survival in patients with primary operable cancer. Approximately 80 studies have evaluated the role of the systemic inflammatory response using biochemical or hematological markers, such as elevated C-reactive protein levels, hypoalbuminemia or increased white cell, neutrophil and platelet counts. Combinations of such factors have been used to derive simple inflammation-based prognostic scores, such as the Gl...

827 citations