The Baseline Ratio of Neutrophils to Lymphocytes Is Associated with Patient Prognosis in Advanced Gastric Cancer

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Abstract

Objective: In cancer patients, the balance between neutrophil (N) and lymphocyte (L) cell counts fluctuates with advancing disease. The objective of our study was to determine the prognostic implications of the N/L ratio in the peripheral blood of gastric cancer patients. Methods: Study participants were identified from a prospective cohort of patients with advanced gastric cancer in Japan (n = 1,220). Results: The median baseline N/L was 2.58 (range, 0.63–12.7). Univariate analysis revealed that patients with an N/L ≧2.5 (n = 644) had a significantly poorer prognosis than those with an N/L <2.5 (n = 576; log rank test, p = 0.019 × 10<sup>–12</sup>). The median survival times for these two groups were 239 (95% confidence interval, CI, 217–251 days) and 363 days (95% CI, 334–406 days), respectively, while the 1-year survival rates were 30 (95% CI, 26–34%) and 50% (95% CI, 45–54%), respectively. A multivariate Cox model established a significant relationship between the N/L ratio and survival (adjusted hazard ratio = 1.52; 95% CI, 1.32–1.75; p = 0.077 × 10<sup>–8</sup>). Conclusions: These results suggest that the N/L ratio is an independent prognostic factor in advanced gastric cancer. Measurement of this ratio may serve as a clinically accessible and useful biomarker for patient survival.

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Differential response of primary and metastatic melanomas to neutrophils attracted by IL-8.

M Oka, Kapaettu Satyamoorthy, Helmut Schaider … (2003)

IL-8 is a strong chemoattractant for neutrophils, and it is constitutively produced by many tumors, including human melanomas. To determine the biologic importance of IL-8 for melanoma cells from primary and metastatic lesions, we transduced selected cell lines constitutively producing low levels of IL-8 with IL-8 cDNA using a replication-deficient adenoviral vector. Nontumorigenic SBcl2 primary melanoma cells formed tumors when transduced with increasing plaque-forming units of IL-8 per cell. However, at high IL-8 transduction levels (100 ng/ml/10(5) cells in 48 hr), tumor growth was impaired due to massive neutrophil infiltration. A similar biphasic response was observed in WM115 primary melanomas, which are tumorigenic but not metastatic. Depletion of neutrophils with an antibody that blocks the accumulation of granulocytes at the site of inflammation enabled transduced primary melanomas secreting high levels of IL-8 to survive and grow. In contrast, highly tumorigenic and metastatic 451Lu cells showed marked increases in tumor growth and number of metastatic foci in the lungs depending on the expression levels of IL-8. Cytotoxicity assays with isolated neutrophils confirmed the preferential killing of primary over metastatic melanoma cells. SBcl2 cells stimulated by IL-8 to form tumors in immunodeficient mice were induced to produce VEGF, suggesting that the angiogenic response is enhanced due to increased growth factor production. Our results demonstrate that nontumorigenic primary melanomas depend on IL-8 stimulation in vivo for growth and that tumor growth depends on the level of neutrophil infiltration. Metastatic melanomas proliferate in vivo independently of infiltrating neutrophils. Copyright 2002 Wiley-Liss, Inc.

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Calcineurin inhibitors acutely improve insulin sensitivity without affecting insulin secretion in healthy human volunteers.

Aaron K. Jorgensen, Lara Aygen Øzbay, Jørgen Rungby … (2012)

New onset diabetes after transplantation is related to treatment with immunosuppressive medications. Clinical studies have shown that risk of new onset diabetes is greater with tacrolimus compared with ciclosporin. The diabetogenicity of ciclosporin and tacrolimus has been attributed to both beta cell dysfunction and impaired insulin sensitivity. This is the first trial to investigate beta cell function and insulin sensitivity using gold standard methodology in healthy human volunteers treated with clinically relevant doses of ciclosporin and tacrolimus. We document that both drugs acutely increase insulin sensitivity, while first phase and pulsatile insulin secretion remain unaffected. This study demonstrates that ciclosporin and tacrolimus have similar acute effects on glucose metabolism in healthy humans. AIM The introduction of calcineurin inhibitors (CNIs) ciclosporin (CsA) and tacrolimus (Tac) has improved the outcome of organ transplants, but complications such as new onset diabetes mellitus after transplantation (NODAT) cause impairment of survival rates. The relative contribution of each CNI to the pathogenesis and development of NODAT remains unclear. We sought to compare the impact of CsA and Tac on glucose metabolism in human subjects. Ten healthy men underwent 5 h infusions of CsA, Tac and saline in a randomized, double-blind, crossover study. During infusion glucose metabolism was investigated using following methods: a hyperinsulinaemic-euglycemic clamp, an intravenous glucose tolerance test (i.v.GTT), glucose-stimulated insulin concentration-time series and indirect calorimetry. Clamp derived insulin sensitivity was increased by 25% during CsA (P < 0.0001) and 13% during Tac administration (P = 0.047), whereas first phase and pulsatile insulin secretion were unaffected. Coinciding with the CNI induced improved insulin sensitivity, glucose oxidation rates increased, while insulin clearance rates decreased, only non-significantly. Tac singularly lowered hsCRP concentrations, otherwise no changes were observed in circulating glucagon, FFA or adiponectin concentrations. Mean blood concentrations of CNIs were 486.9 ± 23.5 µg l(-1) for CsA and 12.8 ± 0.5 µg l(-1) for Tac. Acute effects of i.v. CsA, and to a lesser degree Tac infusions, in healthy volunteers include increased insulin sensitivity, without any effect on first phase or pulsatile insulin secretion. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

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Insulin-like growth factor (IGF) I and II and IGF binding protein (IGFBP) 1, 2 and 3 in serum from patients with Cushing's syndrome.

J Schwander, M Degerblad, W. Blum … (1993)

In the present study of twenty-two patients with Cushing's syndrome, serum insulin-like growth factor (IGF)-I concentrations were normal to high with an increased mean IGF-I concentration, 40% above that of healthy subjects of the same age (p < 0.001). Serum IGF-II concentrations were normal. The morning serum IGF binding protein (IGFBP)-1 concentrations were within the range of healthy controls. IGFBP-1 was inversely correlated to the IGF-I concentration (p < 0.001) and to the 24 h urinary cortisol excretion (p < 0.005) with a combined R squared value of 0.58. In contrast to IGFBP-1, serum IGFBP-2 and IGFBP-3 concentrations were elevated by 1.89 +/- 1.78 SD and 0.92 +/- 0.78 SD (mean +/- 2 SD), respectively. Although increased, the serum IGFBP-2 concentration was inversely correlated to the IGF-I concentration (r = -0.67, p < 0.001). Immunoreactive IGFBP-3 was increased in proportion to IGF-I and the molar ratio [IGFBP-3]:[IGF-I] + [IGF-II] was close to unity (1.04 +/- 0.14), as that of healthy subjects. In serum from patients with Cushing's syndrome, with increased immunoreactive IGFBP-3, there was a corresponding increase in intact glycosylated 40-43 kDa IGFBP-3 as determined by Western ligand blotting. Neutral size chromatography of serum from patients with Cushing's syndrome showed that IGF-I and IGFBP-3 immunoreactivity were predominantly found at the elution volume of the ternary 150 kDa IGF-I/IGFBP-3/acid labile subunit complex and a similar pattern was displayed by normal serum.(ABSTRACT TRUNCATED AT 250 WORDS)

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Author and article information

Journal

Journal ID (publisher-id): OCL

Journal ID (nlm-ta): Oncology

Journal ID (doi): 10.1159/issn.0030-2414

Title: Oncology

Publisher: S. Karger AG

ISSN (Print): 0030-2414

ISSN (Electronic): 1423-0232

Publication date Subscription-year: 2007

Publication date (Print): April 2008

Publication date (Electronic): 17 April 2008

Volume: 73

Issue: 3-4

Pages: 215-220

Affiliations

^aInstitute for Clinical Research, National Kyushu Cancer Center, Fukuoka, Departments of ^bTranslational Clinical Oncology and ^cClinical Trial Design and Management, Graduate School of Medicine, Kyoto University, Kyoto, and ^dTranslational Research Informatics Center, Foundation for Biomedical Research and Innovation, Kobe, Japan

Article

Publisher ID: 127412 Other ID: Oncology 2007;73:215–220

DOI: 10.1159/000127412

PubMed ID: 18424885

SO-VID: bc8824f0-e399-42de-bdca-ee4acd5e73f6

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Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

History

Date received : 21 September 2007

Date accepted : 25 September 2007

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Figures: 2, Tables: 2, References: 20, Pages: 6

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The Baseline Ratio of Neutrophils to Lymphocytes Is Associated with Patient Prognosis in Advanced Gastric Cancer

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Abstract

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Karger: Oncology

Most cited references 7

Differential response of primary and metastatic melanomas to neutrophils attracted by IL-8.

Calcineurin inhibitors acutely improve insulin sensitivity without affecting insulin secretion in healthy human volunteers.

Insulin-like growth factor (IGF) I and II and IGF binding protein (IGFBP) 1, 2 and 3 in serum from patients with Cushing's syndrome.

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Cited by 136

Most referenced authors 213