Toshiji Ishiwata

Osteopontin is involved in the formation of malignant pleural effusion in lung cancer

Malignant pleural effusion (MPE) is associated with advanced-stage lung cancer and is a poor prognostic sign for these patients. Osteopontin (OPN) is a multifunctional cytokine that is involved in the tumor progression and angiogenesis of lung cancer cells. The purpose of this study is to investigate and provide evidence for the role of OPN in the formation of MPE associated with lung cancer. In this study, we established an OPN knockdown murine lung cancer cell line, 3LL cells, utilizing the small interfering RNA (siRNA) technique. To reveal the effect of OPN on the formation of MPE associated with lung cancer, we directly injected OPN knockdown 3LL cells, 3LL/OPN siRNA, or control cells, 3LL/control siRNA, into the pleural space of C57BL/6 mice. OPN knockdown significantly reduced the formation of MPE, but did not inhibit in vivo tumor growth of 3LL cells in mice. Vascular endothelial growth factor (VEGF) concentration in MPE was markedly decreased in the 3LL/OPN siRNA in comparison with that of the 3LL/control siRNA. In vitro, recombinant OPN protein enhanced VEGF secretion from human umbilical vein endothelial cell (HUVEC) or human mesothelial cell line, Met5A cells, in a concentration-dependent manner. These results suggest that OPN is positively involved in the formation of MPE of lung cancer presumably by promoting VEGF secretion from vascular endothelial cells or mesothelial cells. OPN could be an effective target molecule for reducing MPE in lung cancer patients.

Factors influencing weaning from mechanical ventilation in elderly patients with severe pneumonia.

Aims:  The purpose of this study was to determine the factors that adversely affect the weaning of elderly patients with community‐acquired pneumonia from mechanical ventilation.

Thymic adenocarcinoma with sarcomatoid features characterized by intracaval tumor growth: Report of a case

Primary thymic adenocarcinoma is an extremely rare tumor. This report describes a case of thymic adenocarcinoma with a peculiar pathological feature and clinical course. A 54-year-old man complained of cough, dyspnea, and chest pain. Computed tomography scans revealed an anterior mediastinal mass with intracaval growth into the superior vena cava. No definitive diagnosis could be made after several examinations and palliative radiotherapy was performed. He passed away 56 days after the appearance of the initial symptoms. An autopsy revealed that the mediastinal tumor obstructed not only the superior vena cava but also the pulmonary arteries. The histological findings revealed the tumor to be an adenocarcinoma with sarcomatous features. The tumor was immunohistochemically positive for CD5 and negative for thyroid transcription factor-1. These results suggested the tumor to be a thymic adenocarcinoma with sarcomatoid features; furthermore, the tumor invaded the great vessels, thus resulting in a poor prognosis.

A feasibility study of zoledronic acid combined with carboplatin/nedaplatin plus paclitaxel in patients with non-small cell lung cancer with bone metastases.

AIMS AND BACKGROUND Although zoledronic acid (ZOL) has been reported to inhibit bone metastasis from lung cancer, the optimum chemotherapy regimen in combination with ZOL has not yet been determined. METHODS AND STUDY DESIGN Eighteen patients having non-small cell lung cancer (NSCLC) with bone metastasis who received carboplatin/nedaplatin plus paclitaxel combined with ZOL (4 mg every 28 days) were enrolled to investigate the feasibility of this treatment. The efficacy was evaluated by the percentage of patients at 9 months who were receiving radiation therapy, the time to first radiation treatment, and quality of life. Adverse effects were also evaluated. RESULTS Only 3 among 18 patients received radiation therapy for bone metastases during the 9 months of the study. ZOL seems to prolong the median time to the first radiation treatment and maintain the quality of life regarding pain and activity status. No patients discontinued the treatment, although grade 3 or 4 treatment-related adverse effects occurred in 8 patients. CONCLUSIONS ZOL combined with carboplatin/nedaplatin plus paclitaxel is an effective and tolerable treatment for NSCLC with bone metastases.

Improvement in skin color achieved by smoking cessation.

It has been well known that habitual smoking accelerates premature skin ageing recognized as ‘smokers face’. However, the effect of smoking cessation on the appearance of skin has not been elucidated. The aim of this study was to evaluate objectively the effect of smoking cessation on the skins appearance. The stratum corneum carbonyl protein level and skin colour of the cheek and the hand were measured. The change before and during the smoking cessation treatment (0, 2, 4, 8 and 12 weeks), and the success or failure in smoking cessation, was compared and examined. Eighty‐four cases who had smoking cessation treatment were examined. The level of the stratum corneum carbonyl protein did not show any difference comparing before and after treatment for the smoking cessation success group and the failure group. The lightness of skin colour showed an upward tendency 4–12 weeks after starting the treatment in the success group and increased significantly compared with the failure group. The redness showed a significant decrease in comparison with before the treatment, and it also showed a significant decrease compared with the failure group. The yellowness did not show any clear tendency. Also, the haemoglobin showed a decreased tendency. Furthermore, multivariate statistical analysis showed a possibility that the lightness and haemoglobin could be changed by smoking cessation treatment. In conclusion, our study showed that an upward tendency of skin lightness was seen to correspond with a haemoglobin decrease accompanied by smoking cessation. If we can easily measure skin improvement as an effect of smoking cessation, it is thought to be a useful aid for smoking cessation support.

Malignant lymphoma with diffuse cardiac involvement detected by multiple imaging examinations: a case report

IntroductionIn malignant lymphoma, cardiac involvement, which usually forms pathologically focal and firm nodules in the cardiac walls, is considered to be a late manifestation of the disease.Case presentationWe describe the case of a 71-year-old Asian Japanese woman whose first presentation of lymphoma was congestive heart failure. Multiple imaging examinations and laboratory findings led to a presumed diagnosis of a malignant lymphoma. A tissue diagnosis of the mediastinal mass could not be performed due to our patient’s generally poor condition. Our patient received corticosteroid therapy, but died 42 days after her admission. An autopsy revealed lymphoid cells encircling her ventricular wall and infiltrating her endocardium. A histological examination confirmed the diagnosis of diffuse large B-cell lymphoma.ConclusionImaging examinations such as echocardiography, computed tomography with three-dimensional reconstruction, and gallium-67-citrate scintigraphy could clearly detect the diffuse cardiac involvement antemortem. A combination of these imaging techniques could provide a working diagnosis and allow empirical initiation of treatment in patients with poor general condition.

Sex hormones alter Th1 responses and enhance granuloma formation in the lung.

Background: The lung is one of the sites of granulomatous responses, which are characterized by the recruitment and organization of activated macrophages and lymphocytes. There have been several reports that have shown that some pulmonary granulomatous diseases, such as sarcoidosis and nontuberculous mycobacterial disease, are likely to be characterized by a preponderance in postmenopausal females. Although sex hormones have been shown to play an important role in the regulation of the immune system, the influence of sex hormones on pulmonary granuloma formation is still unclear. Objectives: The purpose of this study was to assess whether sex hormones are involved in granulomatous inflammation and to evaluate how sex hormones modulate this response in the lung. Methods: Ovariectomized rats were used as an experimental postmenopausal model in which chronic pulmonary granulomatous inflammation was induced by intravenous injection of complete Freund’s adjuvant. Results: Histological analysis of lung tissues demonstrated enhancement of granuloma formation in the ovariectomized group. Such enhanced granuloma formation was significantly associated with generalized Th1-biased cytokine production in the bronchoalveolar lavage fluid. Conclusion: These results indicate that sex hormones play an important role in pulmonary granuloma formation by altering the Th1 responses.