Salivary cytokine panel indicative of non-small cell lung cancer.

Objective To develop a combinatorial panel of salivary cytokines that manifests the presence of non-small cell lung cancer (NSCLC) that will eventually improve prognosis by facilitating the early diagnosis and management of this common cancer. Methods We performed a case-control study comparing salivary cytokine profiles of 35 adult subjects with NSCLC with those of 35 matched, healthy nonsmokers. Multiplex bead array assays were used to quantify 27 cytokines in saliva, serum, and oral mucosal transudate samples. Logistic regression analysis was used to develop an informative cytokine panel. Receiver operating characteristic (ROC) curves were generated to evaluate the discriminant ability of the panel. Results A combinatorial 12-cytokine panel (interleukin receptor antagonist [IL1RN], IL1B, IL6, IL7, IL8, IL10, C-C motif chemokine ligand 11 [CCL11], tumor necrosis factor, C-X-C motif chemokine ligand 10 [CXCL10], C-C motif chemokine ligand 3, C-C motif chemokine ligand 4, and platelet-derived growth factor-BB) distinguished patients with NSCLC from healthy controls. Further, ROC analysis revealed that a cytokine panel comprising IL10 (odds ratio, 1.156) and CXCL10 (odds ratio, 1.000) discriminated NSCLC with a sensitivity of 60.6% and specificity of 80.8% (area under the ROC curve, 0.701). Conclusion A combinatorial panel of select salivary cytokines indicates the presence of NSCLC

Salivary cytokine panel indicative of non-small cell lung cancer

Objective To develop a combinatorial panel of salivary cytokines that manifests the presence of non-small cell lung cancer (NSCLC) that will eventually improve prognosis by facilitating the early diagnosis and management of this common cancer. Methods We performed a case-control study comparing salivary cytokine profiles of 35 adult subjects with NSCLC with those of 35 matched, healthy nonsmokers. Multiplex bead array assays were used to quantify 27 cytokines in saliva, serum, and oral mucosal transudate samples. Logistic regression analysis was used to develop an informative cytokine panel. Receiver operating characteristic (ROC) curves were generated to evaluate the discriminant ability of the panel. Results A combinatorial 12-cytokine panel (interleukin receptor antagonist [IL1RN], IL1B, IL6, IL7, IL8, IL10, C-C motif chemokine ligand 11 [CCL11], tumor necrosis factor, C-X-C motif chemokine ligand 10 [CXCL10], C-C motif chemokine ligand 3, C-C motif chemokine ligand 4, and platelet-derived growth factor-BB) distinguished patients with NSCLC from healthy controls. Further, ROC analysis revealed that a cytokine panel comprising IL10 (odds ratio, 1.156) and CXCL10 (odds ratio, 1.000) discriminated NSCLC with a sensitivity of 60.6% and specificity of 80.8% (area under the ROC curve, 0.701). Conclusion A combinatorial panel of select salivary cytokines indicates the presence of NSCLC.ArticleJOURNAL OF INTERNATIONAL MEDICAL RESEARCH.46(9):3570-3582(2018)journal articl

Effects of a synthetic protease inhibitor (gabexate mesilate) and a neutrophil elastase inhibitor (sivelestat sodium) on acid-induced lung injury in rats

The present study was designed to examine the combined effects of a synthetic protease inhibitor, gabexate mesilate, with a specific neutrophil elastase inhibitor, sivelestat sodium, on acid-induced lung injury. Adult male Sprague-Dawley rats weighing 300-350 g were anaesthetised intraperitoneally with pentobarbitone sodium and the right jugular vein was cannulated. Following tracheostomy, rats were ventilated mechanically and underwent intratracheal instillation of hydrochloric acid (HCl, 0.1 N 1.5 ml/kg) or normal saline. Gabexate mesilate (10 mg/kg, i.p.) and/or sivelestat sodium (10 mg/kg/h, i.v.) were administered 30 min before HCl instillation. Bronchoalveolar lavage fluid samples were obtained 5 h after HCl instillation. in bronchoalveolar lavage fluid, the HCl-induced increases in total nucleated cell counts, neutrophil counts, optical density at 412 nm as an index of pulmonary haemorrhage, concentrations of albumin and cytokine-induced neutrophil chemoattractant (CINC) were significantly attenuated by either gabexate mesilate or sivelestat sodium treatment. Gabexate mesilate or sivelestat sodium treatment also significantly attenuated the wet to dry weight ratio induced by HCl. However, combined treatment with both gabexate mesilate and sivelestat sodium did not show additive effects on HO-induced lung injury, compared with single treatments. These findings suggested that gabexate mesilate and sivelestat sodium each exhibited protective effects on acid-induced lung injury, but that synergistic effects of both agents are limited in this acid-induced lung injury model.ArticleEUROPEAN JOURNAL OF PHARMACOLOGY. 641(2-3):220-225 (2010)journal articl

Comparisons of different mean airway pressure settings during high-frequency oscillation in inflammatory response to oleic acid-induced lung injury in rabbits

Koichi Ono1, Tomonobu Koizumi2, Rikimaru Nakagawa1, Sumiko Yoshikawa2, Tetsutarou Otagiri11Department of Anesthesiology and Resuscitation; 2First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, JapanPurpose: The present study was designed to examine effects of different mean airway pressure (MAP) settings during high-frequency oscillation (HFO) on oxygenation and inflammatory responses to acute lung injury (ALI) in rabbits.Methods: Anesthetized rabbits were mechanically ventilated with a conventional mechanical ventilation (CMV) mode (tidal volume 6 ml/kg, inspired oxygen fraction [FIo2] of 1.0, respiratory rate [RR] of 30/min, positive end-expiratory pressure [PEEP] of 5 cmH2O). ALI was induced by intravenous administration of oleic acid (0.08 ml/kg) and the animals were randomly allocated to the following three experimental groups; animals (n = 6) ventilated using the same mode of CMV, or animals ventilated with standard MAP (MAP 10 cmH2O, n = 7), and high MAP (15 cmH2O, n = 6) settings of HFO (Hz 15). The MAP settings were calculated by the inflation limb of the pressure-volume curve during CMV.Results: HFO with a high MAP setting significantly improved the deteriorated oxygenation during oleic acid-induced ALI and reduced wet/dry ratios, neutrophil counts and interleukin-8 concentration in bronchoalveolar lavage fluid, compared to those parameters in CMV and standard MAP-HFO.Conclusions: These findings suggest that only high MAP setting during HFO could contribute to decreased lung inflammation as well as improved oxygenation during the development of ALI.Keywords: lung protective ventilation, open lung ventilation, IL-8, neutrophi

Relationship between Physical Activity and Health-related Quality of Life in Hospitalized and Terminally Ill Cancer Patients

Article信州医学雑誌 68(3): 149-157(2020)journal articl

Comparison of acid-induced inflammatory responses in the rat lung during high frequency oscillatory and conventional mechanical ventilation

The present study was performed to compare the effects of high frequency oscillatory ventilation (HFOV) with conventional mechanical ventilation (CMV) on pulmonary inflammatory responses in a rat acid-induced lung injury model. Anesthetized rats were instilled intratracheally with HCl (0.1 N, 2 mL/kg) and then randomly divided into three mechanical ventilation settings: HFOV (an oscillatory frequency of 15 Hz, mean airway pressure (MAP) of 9 cmH(2)O), CMV at tidal volume of 12 and 6 mL/kg for 5 h. After HCl instillation, HFOV significantly attenuated the increases in neutrophil infiltration and TNF-alpha concentration in bronchoalveolar lavage fluid compared with the CMV groups. During HFOV, there was an inhibition of an increase in TNF-alpha mRNA expression and a decrease in SP-A mRNA expression induced by acid instillation. This animal study demonstrates that HFOV is a suitable form of mechanical ventilation to prevent inflammatory responses in acid-induced lung injury.ArticleINFLAMMATION RESEARCH. 59(11):931-937 (2010)journal articl

Diffuse Endobronchial Wall Spread of Metastatic Breast Cancer

We present here a case of diffuse tracheobronchial wall spread of metastatic breast cancer who was successfully treated with trastuzumab plus vinorelbine chemotherapy. The patient had a left radical mastectomy for breast cancer in March 2000 and developed persistent cough and dyspnea in November 2006. Pulmonary function test demonstrated an obstructive pattern. Chest computed tomography showed a wall thickening of trachea and right side bronchus, but radiographic findings including 18F-fluorodeoxyglucose positron emission tomography failed to detect the locations of disease in the lung. The findings on bronchofiberscopy showed edematous tracheobronchial mucosa, but also failed to visually detect direct masses. Transbronchial biopsy specimens revealed involvement of metastatic breast cancer. The patient was treated with trastuzumab plus vinorelbine chemotherapy and the wall thickening of bronchial tree and clinical symptoms were improved. Although endobronchial metastasis in metastatic breast cancer is not uncommon, diffuse spread without forming intraluminal mass is extremely rare. The pattern of endobronchial metastasis should be considered in patients with malignancies even when radiographic abnormalities are undetectable

Clinical characteristics and outcomes of patients with small cell lung cancer detected by CT screening

The present study was performed to evaluate the clinical characteristics and survival outcomes in patients with small cell lung cancer (SCLC) detected by low-dose computed tomography (CT). We retrospectively reviewed clinical records of patients with SCLC treated at our hospital between 1997 and 2011 and selected patients with SCLC detected by CT screening. We identified 12 patients (male/female 11/1; mean age 67.8 years old. Nine patients had limited disease (LD), and 3 had extensive disease (ED). Five LD patients underwent thoracic surgery, and the pathological staging information included stage IA (n = 1), IB (n = 1), IIA (n = 1), and IIIB (n = 2). Although 2 patients with pathological stages IA and IB had >10-year survival, the median survival times (MST) in LD and ED were 25 months (95 % CI 17.0-32.9) and 16 months (95 % CI; not evaluated), respectively. In addition, MST in 12 patients was not significantly different from that in SCLC patients in general care in our hospital. This analysis suggested that CT screening contributes to the detection of early-stage SCLC in patients that are potentially suitable for surgery, but it remains unclear how to improve clinical outcome in patients with SCLC.ArticleMEDICAL ONCOLOGY. 30(3):623 (2013)journal articl

Phase II Trial of Biweekly Paclitaxel and Gemcitabine as Second-Line Chemotherapy for Non-Small Cell Lung Cancer Previously Treated with Platinum-Based Chemotherapy

A phase II study was conducted to evaluate the feasibility and efficacy of biweekly administration of paclitaxel and gemcitabine in patients with non-small cell lung cancer (NSCLC) who had been treated previously with platinum-based chemotherapy. Paclitaxel (150 mg/m2) and gemcitabine (1,000 mg/m2) were administered biweekly for at least 4 cycles. Thirty-one patients with a median age of 64 years (39-75 years) were enrolled in this study(stage IIIB/IV :11/20,PS 0/1/2:13/16/2).Partial response was observed in 7 cases (23%), and stable disease was seen in 18 cases (58%).Median survival time was 8.8 months with a one-year survival rate of 41.9 %.Hematological toxicities were mild and neutropenia of grade 3 or above was observed in one patient (3%). Non-hematological toxicities were also mild, including neurotoxicity (3%). Biweekly paclitaxel and gemcitabine combination chemotherapy was effective and tolerated well as second-line therapy against NSCLC.Article信州医学雑誌 59(6): 411-418(2011)departmental bulletin pape

A Case of Olfactory Neuroblastoma (Esthesioneuroblastoma)Presenting with Anemia Due to Nasal Bleeding

Article信州医学雑誌 64(5): 247-252(2016)journal articl