• Asian Pacific Journal of Cancer Prevention
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• v.17 no.sup3
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• pp.299-304
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• 2016

Cytolethal distending toxin (CDT) is a secreted tripartite genotoxin produced by many pathogenic gram-negative bacteria. It is composed of three subunits, CdtA, CdtB and CdtC, and CdtB-associated deoxyribonuclease (DNase) activity is essential for the CDT toxicity. In the present study, to design a novel potentially antitumor drug against lung cancer, the possible mechanisms of cdtB anticancer properties were explored in the A549 human lung adenocarcinoma cell line. A recombinant plasmid pcDNA3.1/cdtB was constructed expressing CdtB of human periodontal bacterium Aggregatibacter actinomycetemcomitans and investigated for toxic properties in A549 cells and possible mechanisms. It was observed that plasmid pcDNA3.1/cdtB caused loss of cell viability, morphologic changes and induction of apoptosis. Furthermore, measurement of caspase activity indicated involvement of an intrinsic pathway of cell apoptosis. Consequently, the recombinant plasmid pcDNA3.1/cdtB may have potential as a new class of therapeutic agent for gene therapy of lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.875-880
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• 2015

Mediator 19 (Med19) is a component of the mediator complex which is a coactivator for DNA-binding factors that activate transcription via RNA polymerase II. Accumulating evidence has shown that Med19 plays important roles in cancer cell proliferation and tumorigenesis. The involvement of Med19 in sensitivity to the chemotherapeutic agent cisplatin was here investigated. We employed RNA interference to reduce Med19 expression in human non-small cell lung cancer (NSCLC) cell lines and analyzed their phenotypic changes. The results showed that after Med19 siRNA transfection, expression of Med19 mRNA and protein was dramatically reduced (p<0.05). Meanwhile, impaired growth potential, arrested cell cycle at G0/G1 phase and enhanced sensitivity to cisplatin were exhibited. Apoptosis and caspase-3 activity were increased when cells were exposed to Med19 siRNA and/or cisplatin. The present findings suggest that Med19 facilitates tumorigenic properties of NSCLC cells and knockdown of Med19 may be a rational therapeutic tool for lung cancer cisplatin sensitization.

• Radiation Oncology Journal
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• v.35 no.1
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• pp.16-24
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• 2017

Locally advanced non-small cell lung cancer (LA-NSCLC) is composed of heterogeneous subgroups that require a multidisciplinary team approach in order to ensure optimal therapy for each patient. Since 2010, the National Comprehensive Cancer Network has recommended chemoradiation therapy (CRT) for bulky mediastinal disease and surgical combination for those patients with single-station N2 involvement who respond to neoadjuvant therapy. According to lung cancer tumor boards, thoracic surgeons make a decision on the resectability of the tumor, if it is determined to be unresectable, concurrent CRT (CCRT) is considered the next choice. However, the survival benefit of CCRT over sequential CRT or radiotherapy alone carries the risk of additional toxicity. Considering severe adverse events that may lead to death, fit patients who are able to tolerate CCRT must be identified by multidisciplinary tumor board. Decelerated approaches, such as sequential CRT or high-dose radiation alone may be a valuable alternative for patients who are not eligible for CCRT. As a new treatment strategy, investigators are interested in the application of the innovative radiation techniques, trimodality therapy combining surgery after high-dose definitive CCRT, and the combination of radiation with targeted or immunotherapy agents. The updated results and on-going studies are thoroughly reviewed in this article.

• IMMUNE NETWORK
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• v.5 no.1
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• pp.36-44
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• 2005

Background: The anti-tumor therapeutic effect of autologous tumor cell lysate pulseddendritic cells (DCs) was studied for non-immunogenic and immune suppressive lung cancer model. To test the possibility as an adjuvant therapy, minimal residual disease model was considered in mouse in vivo experiments. Methods: Syngeneic 3LL lung cancer cells were inoculated intravenously into the C57BL/6 mouse. Autologous tumor cell (3LL) or allogeneic leukemia cell (WEHI-3) lysate pulsed-DCs were injected twice in two weeks. Intraperitoneal DC injection was started one day (MRD model) after tumor cell inoculation. Two weeks after the final DC injection, tumor formation in the lung and the tumor-specific systemic immunity were observed. Tumor-specific lymphocyte proliferation and the IFN-${\gamma}$ secretion were analyzed for the immune monitoring. Therapeutic DCs were cultured from the bone marrow myeloid lineage cells with GM-CSF and IL-4 for 7 days and pulsed with tumor cell lysate for 18 hrs. Results: Compared to the saline treated group, tumor formation was suppressed in 3LL tumor cell lysate pulsed-DC treated group, while 3LL-specific immune stimulation was minimum. WEHI-3-specific immune stimulation occurred in WEHI-3 lysate-pulsed DC treated group, which had no correlation with tumor regression. Conclusion: The data suggest the possible anti-tumor effect of cultured DCs as an adjuvant therapy for minimal residual disease state of lung cancer. The significance of immune modulation in DC therapy including the possible involvement of NK cell as well as antigen-specific cytotoxic T cell activity induction was discussed.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.4063-4070
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• 2016

Background: Cytochrome P450 2E1 (CYP2E1) and catechol-O-methyltransferase (COMT) genes may contribute to susceptibility to lung cancer because of their critical involvement in mechanisms of carcinogenesis. Materials and Methods: We evaluated the role of CYP2E1 rs2031920 and COMT rs4680 in a case-control study involving 462 lung cancer cases and 379 controls in Japanese. Logistic regression was used to assess adjusted odds ratios (OR) and 95% confidence intervals (CI). Multiplicative and additive interactions with cigarette smoking or alcohol use were also examined. Results: Neither CYP2E1 rs2031920 nor COMT rs4680 was associated with lung cancer risk overall. However, smokers with the CC genotype of CYP2E1 rs2031920 (OR = 3.57, 95% CI = 2.26 - 5.63) presented a higher risk of lung cancer than those with at least one T allele (OR = 2.91, 95% CI = 1.70 - 4.98) as compared to never-smokers with at least one T allele (reference). Subjects with excessive drinking and the CC genotype of CYP2E1 rs2031920 had a significantly higher risk (OR = 2.22, 95% CI =1.39 - 3.56) than appropriate drinkers with at least one T allele. A similar tendency was observed between COMT rs4680 and either smoking or drinking habits. There were no multiplicative or additive interactions between the polymorphisms and either smoking or alcohol use. Conclusions: Our findings indicate that CYP2E1 rs2031920 and COMT rs4680 are not major contributors to lung cancer risk in our Japanese population. Future studies on the genetics of lung cancer in Japanese and their environment interactions are required.

• Tuberculosis and Respiratory Diseases
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• v.78 no.3
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• pp.258-261
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• 2015

Eosinophilic lung diseases are heterogeneous disorders characterized by varying degrees of pulmonary parenchyma or blood eosinophilia. Causes of eosinophilic lung diseases range from drug ingestion to parasitic or fungal infection as well as idiopathic. The exact pathogenesis of eosinophilic lung disease remains unknown. Urushiol chicken can frequently cause allergic reactions. Contact dermatitis (both local and systemic) represents the most-common side effect of urushiol chicken ingestion. However, there has been no previous report of lung involvement following urushiol chicken ingestion until now. A 66-year-old male was admitted to our hospital with exertional dyspnea. Serial chest X-ray revealed multiple migrating infiltrations in both lung fields, with eosinophilic infiltration revealed by lung biopsy. The patient had ingested urushiol chicken on two occasions within the 2 weeks immediately prior to disease onset. His symptoms and migrating lung lesions were resolved following administration of oral corticosteroids.

• Tuberculosis and Respiratory Diseases
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• v.74 no.6
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• pp.274-279
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• 2013

Sarcoidosis is a multisystemic disorder of unknown cause that is characterized pathologically by noncaseating granulomas. Diagnosis is based on the exclusion of other infectious, interstitial, and neoplastic diseases and on the typical pathology. Although the lungs and mediastinal lymph nodes are almost involved, endobronchial nodular lesions of sarcoidosis with lung involvements are rare. We report a case of sarcoidosis with lung involvements and endobronchial nodules as confirmed by bronchial biopsy.

• Tuberculosis and Respiratory Diseases
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• v.79 no.3
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• pp.188-192
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• 2016

Antisynthetase syndrome has been recognized as an important cause of autoimmune inflammatory myopathy in a subset of patients with polymyositis and dermatomyositis. It is associated with serum antibody to aminoacyl-transfer RNA synthetases and is characterized by a constellation of manifestations, including fever, myositis, interstitial lung disease, mechanic's hand-like cutaneous involvement, Raynaud phenomenon, and polyarthritis. Lung disease is the presenting feature in 50% of the cases. We report a case of a 60-year-old female with acute respiratory distress syndrome (ARDS), which later proved to be an unexpected and initial manifestation of anti-Jo-1 antibody-positive antisynthetase syndrome. The present case showed resolution of ARDS after treatment with high-dose corticosteroids. Given that steroids are not greatly beneficial in the treatment of ARDS, it is likely that the improvement of the respiratory symptoms in this patient also resulted from the prompt suppression of the inflammatory systemic response by corticosteroids.

• Clinics in Shoulder and Elbow
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• v.18 no.1
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• pp.43-46
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• 2015

Pancoast syndrome (PS) is characterized by a malignant neoplasm of the superior sulcus of the lung with destructive lesions of the thoracic inlet and involvement of the brachial plexus and cervical sympathetic nerves. The most common initial symptom of PS is shoulder pain; however, cough, dyspnea, and hemoptysis, signs often associated with lung cancer, are not as common. Investigation of PS can be difficult even with plain radiographs of the chest because it is surrounded by osseous structures such as the ribs, vertebral bodies, and manubrium. Due to these characteristics, orthopedic surgeons tend to make a misdiagnosis resulting in delay of appropriate treatment. Here we report on a patient who was supposed to undergo rotator cuff repair for his shoulder pain and weakness, and was eventually diagnosed with PS.

• Journal of Chest Surgery
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• v.24 no.8
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• pp.830-835
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• 1991

Tuberculosis is a chronic disease caused by Mycobacterium tuberculosis, which usually affects the lung but may cause lesions in any organ or tissue of the human body. Mediastinal lymph node involvement is common feature of intrathoracic tuberculosis in children. Sometimes the lymph node may be enlarged and it causes compressive symptoms. Recently we experienced two cases of tuberculous abscess at middle mediastinum. The abscess seemed to be originated from the mediastinal lymphadenitis, and caused the symptoms. Operation was performed by median sternotomy and by posterolateral thoracotomy incision respectively for the purpose of relieving symptoms and diagnosing the mediastinal mass. The symptoms were relieved completely and postoperative course was uneventful.