Gen Ohara

Interleukin-33 induces interleukin-17F in bronchial epithelial cells.

IL‐33 is clearly expressed in the airway of patients with asthma, but its role in asthma has not yet been fully understood. IL‐17F is also involved in the pathogenesis of asthma. However, the regulatory mechanisms of IL‐17F expression remain to be defined. To further indentify the role of IL‐33 in asthma, we investigated the expression of IL‐17F by IL‐33 in bronchial epithelial cells and its signaling mechanisms.

Lung cancer in patients aged 80 years and over

OBJECTIVES The purpose of this study is to examine clinical and pathological features, treatment modality approaches in the elderly, especially in patients aged 80 years and older. METHODS From the databases at two educational hospitals during the period from January 1978 and December 2007, medical records of lung cancer patients were retrospectively reviewed. The patient population was divided into three age groups: less than 70 years (the <70 age group), 70-79 years (the 70-79 age group), and 80 years or older (the > or =80 age group). Time trends were also studied in two-time intervals: first study period up to 1997, which represents past practice standards, the second study period up to 2007, which represents contemporary practice. RESULTS Patients aged 80 years and older comprised 7.5% of 2775 consecutive patients with lung cancer, and there was a rapid increase in the proportion of patients aged 80 years or older from the earlier to the later time period. The > or =80 age group had higher proportion of poor performance status (PS) and comorbid disease than the <70 age group and the 70-79 age group. Unchanged proportion of patients with poor PS and advanced disease at presentation were observed in the > or =80 age group. The > or =80 age group was less likely to be subjected to surgery or chemotherapy, and had inferior outcomes when compared with the 70-79 age group and the <70 age group. Survival improvement was not observed in the > or =80 age group. Multivariate analysis showed good PS, early clinical stage and surgery were favorable prognostic factors in the > or =80 age group. CONCLUSION In order to improve the outcome, detection of early stage lung cancer in patients with good PS and thorough pretreatment evaluation for appropriate treatment are indeed essential even for the > or =80 age group of patients.

Induction of insulin-like growth factor-I by interleukin-17F in bronchial epithelial cells

Cite this as: M. Kawaguchi, J. Fujita, F. Kokubu, G. Ohara, S‐K Huang, S. Matsukura, Y. Ishii, M. Adachi, H. Satoh and N. Hizawa, Clinical & Experimental Allergy, 2010 (40) 1036–1043.

IL-17F Induces CCL20 in Bronchial Epithelial Cells

IL-17F plays a crucial role in airway inflammatory diseases including asthma, but its function has not been fully elucidated. CCL20 is also involved in allergic airway inflammation, while its regulatory mechanisms remain to be defined. To further identify a novel role of IL-17F, the expression of CCL20 by IL-17F in bronchial epithelial cells and the signaling mechanisms involved were investigated. Bronchial epithelial cells were stimulated with IL-17F, and the levels of CCL20 gene and protein measured, with the effects of the addition of various kinase inhibitors and siRNAs also investigated. IL-17F significantly induced the expression of CCL20 gene and protein. Pretreatment with inhibitors for MEK1/2, Raf1 and MSK1, and overexpression of a Raf1 dominant-negative mutant significantly diminished IL-17F-induced CCL20 production. Moreover, transfection of the siRNAs targeting MSK1, p90RSK, and CREB blocked CCL20 expression. These findings suggest that IL-17F is able to induce CCL20 via Raf1-MEK1/2-ERK1/2-MSK1/p90RSK-CREB signaling pathway in bronchial epithelial cells. The IL-17F/CCL20 axis may be a novel pharmacological target for asthma.

Chemotherapy for Langerhans cell sarcoma

We read with interest the case report by Uchida et al. on successful chemotherapy of a Langerhans cell sarcoma. According to them, chemotherapy is commonly employed as palliative treatment in patients with advanced sarcomas, whereas neoadjuvant or adjuvant treatment must be considered investigational. In their case, chemotherapy was started using mesna, doxorubicin, ifosfamide, and dacarbazine (MAID) based on the results of a Phase II clinical trial described by Elias et al. We recently experienced a similar case, in which the diagnosis was pleomorphic carcinoma of the lung. The patient continues to respond to gemcitabine and vinorelbine. We are interested in the reasoning as to why the patient in the Uchida et al. case was treated with MAID. The authors noted that they recommended the use of the MAID regimen to their patient based on the dramatic response and success of this protocol. However, the Phase II study by Elias et al. included patients with various kinds of sarcoma. In addition, previous patients with Langerhans cell sarcoma were mainly treated with CHOP or modifi ed CHOP regimens, as the authors presented in Table 1 in their article. We would like to know why the authors selected the MAID protocol, and we would appreciate hearing from the authors of the most appropriate chemotherapeutic regimen for this rare disease.

Patients With Lung Cancer With Metachronous or Synchronous Gastric Cancer

BACKGROUND There are few reports of treatment and outcome for patients with metachronous or synchronous lung and gastric cancers. To evaluate them, we conducted a retrospective study. PATIENTS AND METHODS The medical records of patients with lung cancer who previously or simultaneously had gastric cancer seen in our division between January 1979 and July 2008 were reviewed. RESULTS Forty-five (3.2%) of 1391 patients had previous or simultaneous gastric cancer. The proportion of men was higher among patients with lung cancer with gastric cancer than those without (P = .0006). There was a significant difference in age at the time of diagnosis of lung cancer between the 45 patients with gastric cancer and the 1346 patients without it (P = .0344). The proportion of smokers was higher among lung cancer patients with gastric cancer than those without (P = .0015). Twenty-seven of 45 patients had smoking-related cell types of lung cancer: squamous cell carcinoma and small-cell lung cancer. The proportion of these 2 cell types was higher in patients with lung cancer with gastric cancer than those without (P = .02). The diagnosis of gastric cancer preceded the diagnosis of lung cancer in 33 patients, and the median duration from the diagnosis of gastric cancer to that of the lung cancer was 6 years. CONCLUSION For patients with gastric cancer, smoking cessation, a chest radiograph at least yearly for several years, and swift evaluation of signs or symptoms that are suggestive of lung cancer should be recommended, especially in elderly men with gastric cancer and smoking habit.

Acute-onset type 1 diabetes mellitus caused by nivolumab in a patient with advanced pulmonary adenocarcinoma.

A case of acute‐onset type 1 diabetes mellitus concomitant with pneumonitis and vitiligo is described.

Peritoneal and meningeal relapse from lung adenocarcinoma after a response to gefitinib: A case report

The prognosis of carcinomatous peritonitis and meningitis is poor since ascites and focal neurological dysfunctions usually do not improve despite the available treatment options for this devastating disease. This is a case report of peritoneal and meningeal relapse from lung adenocarcinoma following a response to gefitinib. A 72-year-old woman was diagnosed with adenocarcinoma in the upper lobe of the left lung, accompanied by a massive carcinomatous pleural effusion. Following a cisplati-based chemotherapy, gefitinib was initiated, achieving satisfactory disease control. At 8 months after gefitinib initiation, the patient developed abdominal distension, gait disturbance and visual disorder of the right eye. Adenocarcinoma cells were detected in the ascitic and pleural fluids. The findings of this case report suggest that clinicians should remain vigilant for this type of metastasis, although it is rarely encountered.

Recovery from carcinomatous meningitis by erlotinib.

Treatment options include whole-brain irradiation, systemic chemotherapy, and intrathecal chemotherapy such as methotrexate [2]. Despite these measures, the prognosis is poor with a median survival of 2–3 months, and focal neurologic dysfunctions do not improve in most cases [1]. The benefit of EGFR tyrosine kinase inhibitors (TKIs) in the treatment of carcinomatous meningitis in patients with nonsmall-cell lung cancer (NSCLC) has recently attracted attention, although all publications were only case reports or case series [3–10]. Erlotinib is widely used in patients with advanced NSCLC and its clinical utility is now highly evaluated [5]; there are reports observing that erlotinib was effective in carcinomatous meningitis after the failure of gefitinib treatment [4, 6]. It is well known that the serum concentration of erlotinib is several times higher than that of gefitinib [6]. It is not likely that gefitinib, when administrated at 250 mg/day, can achieve adequate levels in the central nervous system (CNS); therefore, higher doses of gefitinib may be necessary. Very recently, 2 research groups determined the concentrations of erlotinib in plasma and the cerebrospinal fluid (CSF) and confirmed that there was a measurable penetration of erlotinib into the CSF [9, 10]. This observation suggests that erlotinib may be a therapeutic option for patients with carcinomatous meningitis developing during gefitinib treatment. As the patient had a rapid onset of symptoms, she received erlotinib rather than gefitinib in order to achieve adequate therapeutic concentrations within the CNS. In summary, we report on a rare case of NSCLC-related carcinomatous meningitis successfully treated with erlotinib.

Chronic Eosinophilic Pneumonia with Subpleural Curvilinear Shadow

We report a rare case of chronic eosinophilic pneumonia with subpleural curvilinear shadow. CT scan showed a patchy consolidation in the bilateral upper lungs. In addition, subpleural curvilinear shadow was found in the bilateral upper lungs. A bronchoalveolar lavage obtained from the right middle lobe showed 25 % eosinophils. Although very rare, we should therefore keep in mind that patients, who have patchy consolidation with areas of subpleural curvilinear shadow in the bilateral upper lungs, may have chronic eosinophilic pneumonia.