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Takeshi Hanagiri,
Yoshiki Shigematsu, Shinji Shinohara,
Masaru Takenaka,
Sohich Oka,
Yasuhiro Chikaishi,
Yoshika Nagata,
Tetsuro Baba,
Hidetaka Uramoto,
Tomoko So,
Sohsuke Yamada
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ABSTRACT: Aim: The purpose of this study was to investigate the clinical significance of expression of cancer/testis (CT) antigen and down-regulation of HLA class-I in patients with stage I non-small cell lung cancer (NSCLC), which underwent complete surgical resection.
The expression of HLA class-I molecules was evaluated in 136 resected NSCLC specimens by immunohistochemistry. The results were scored as the percentage of stained tumor cells and categorized into two groups: 0-79%, reduced expression; and >80%, normal expression. The expression of CT antigen was performed by reverse transcription-polymerase chain reaction (RT-PCR).
The expression of HLA class-I was normal in 49 tumors (36%), and there was reduced expression in 87 tumors (64%). The expression of Melanoma antigen (MAGE)-A3, MAGE-A4, and Kita-Kyushu lung cancer antigen-1 (KK-LC-1) was positive in 34 (25.0%), 22 (16.2%), and 42 (30.9%) patients, respectively. There was no significant difference in the proportion of HLA class-I expression associated with the expression of any of the CT antigens. Among the patients with positive expression of at least one of the CT antigens, the 5-year survival rate of the patients with the normal expression of HLA class-I was 87.5%; however, it was 63.4% in patients with the reduced expression of HLA class-I (p=0.0477).
Reduced expression of HLA class-I was an unfavorable prognostic factor in patients with positive expression of CT antigen, and represents an important hurdle to antigen-based cancer immunotherapy.
Anticancer research 05/2013; 33(5):2123-8. · 1.73 Impact Factor
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Masaru Takenaka,
Takeshi Hanagiri, Shinji Shinohara,
Manabu Yasuda,
Yasuhiro Chikaishi,
Soich Oka,
Hidehiko Shimokawa,
Yoshika Nagata,
Makoto Nakagawa,
Hidetaka Uramoto,
Tomoko So,
Sohsuke Yamada,
Fumihiro Tanaka
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ABSTRACT: BACKGROUND: OPN is a multifunctional glycophosphoprotein originally described as a secreted protein from malignant epithelial cells. This study focused on the clinical significance of preoperative serum level of OPN in NSCLC patients who underwent a complete resection. PATIENTS AND METHODS: The serum OPN level was assayed in 244 patients who underwent a complete resection of NSCLC by commercially available sandwich enzyme-linked immunosorbent assay kits. The patients were considered as a higher group, when the serum OPN levels exceeded 81.3 ng/mL. RESULTS: The patients included 166 male and 78 female subjects. The histologic types included 172 adenocarcinomas, 49 squamous cell carcinomas, and 23 other types of carcinoma. The serum level of OPN in male patients (92.6 ng/mL) was significantly higher than that of female patients (76.9 ng/mL). The OPN level of squamous cell carcinoma was significantly higher than that of adenocarcinoma. The OPN level was significantly elevated in patients with the pleural invasion or microvascular invasion than those without the invasion. The 5-year survival rate after surgery in the lower OPN group (82.0%) was a significant favorable prognosis than that in the higher OPN group (63.7%) (P < .0001). The 5-year survival rates in the lower OPN group at stage I NSCLC (88.1%) was significantly better than that in the higher OPN group (80.5%) (P = .0321). CONCLUSION: The preoperative serum OPN level was a useful predictor of an unfavorable prognosis, and it was found to be an independent prognostic determinant of outcome in patients who underwent surgery for NSCLC.
Clinical Lung Cancer 10/2012; · 2.94 Impact Factor
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Shinji Shinohara,
Takeshi Hanagiri,
Tetsuya So,
Manabu Yasuda,
Masaru Takenaka,
Yoshika Nagata,
Hidehiko Shimokawa,
Makoto Nakagawa,
Hidetaka Uramoto,
Tomoko So,
Fumihiro Tanaka
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ABSTRACT: Thymomas are relatively rare tumors. In this study, we investigated the clinical features of patients who underwent surgical resection for thymoma.
This study clinicopathologically evaluated 54 consecutive patients who underwent a surgical resection of thymoma in our department between 1994 and 2006.
A complete resection was performed in 52 patients, while two patients underwent an incomplete resection due to pleural dissemination. Combined resection with adjacent organs was performed for the lung (n=6), pericardium (n=5), and large vessels (brachiocephalic vein in three, superior vena cava in two). The concomitant autoimmune diseases were observed in 20 patients (37%), and they included myasthenia gravis in 17 patients, macroglobulinemia in one, pemphigus vulgaris in one, and stiff person syndrome in one patient. The histologic types of the World Health Organization classification diagnosed as type A in four patients, type AB in 14, type B1 in eight, type B2 in 15, and type B3 in 11. There were 27, 17, eight, and two patients with Masaoka stages I, II, III, and IV, respectively. Four patients died, and the causes of death included recurrence of thymoma in two, gastric carcinoma in one, and respiratory failure due to myasthenia gravis in one patient. The overall survival rate at 10 years was 94.6% in patients with stages I and II disease and 77.1% in patients with stages III and IV disease.
Long-term survival can be expected not only for patients at early stages, as well as for patients with stages III and IV disease if surgical resection is completed macroscopically.
Asian Journal of Surgery 10/2012; 35(4):144-8. · 0.57 Impact Factor
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Takeshi Hanagiri, Shinji Shinohara,
Masaru Takenaka,
Yoshiki Shigematsu,
Manabu Yasuda,
Hidehiko Shimokawa,
Yoshika Nagata,
Makoto Nakagawa,
Hidetaka Uramoto,
Tomoko So,
Fumihiro Tanaka
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ABSTRACT: Hyaluronic acid (HA) has been proposed as a biochemical marker of malignant pleural mesothelioma (MPM). The present study focused on the implications of HA and CD44 interaction in the proliferation and invasiveness of MPM. The proliferation and invasive activity was evaluated in two human mesothelioma cell lines, ACC-MESO-1 and K921MSO, by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and the transwell chamber model. The knockdown of CD44 gene expression was accomplished by transfection of the cells with small interfering RNA. Flow cytometry revealed that both the ACC-MESO-1 and K921MSO cell lines highly expressed CD44. Treatment with HA enhanced the proliferation in both mesothelioma cell lines in comparison to cells without HA treatment. The treatment with HA (25 μg/ml) also significantly upregulated the invasion of both types of cells. The silencing of CD44 significantly abrogated the effect of HA treatment on the proliferation of ACC-MESO-1 cells and significantly suppressed the proliferation of K921MSO cells. HA-CD44 binding is important for the migration and proliferation of mesothelioma cells. Therefore, the HA-CD44 interaction is a potentially useful therapeutic target in MPM.
Tumor Biology 08/2012; · 1.94 Impact Factor
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Shinji Shinohara,
Daisuke Korenaga,
Ai Edagawa,
Kenichi Koushi,
Shinji Itoh,
Hirofumi Kawanaka,
Daihiko Eguchi,
Katsumi Kawasaki,
Toshiro Okuyama,
Yasuharu Ikeda,
Kenji Takenaka
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ABSTRACT: PURPOSES: The purpose of this study was to determine an effective treatment strategy for patients with Stage IV gastric cancer. METHODS: We analyzed the significant prognostic factors in 74 patients who underwent surgery between 1989 and 2005, and were finally determined to have Stage IV gastric cancer. These patients were classified as curability A (n = 0), B (n = 29) and C (n = 45) according to the criteria outlined by Japanese Gastric cancer society. Anti-tumor drugs were used after surgery in some cases. There were 32 patients who received either no treatment or an oral anti-tumor drug, and 42 patients who received new chemotherapeutic regimens. RESULTS: According to a univariate analysis, the postoperative mean survival times were significantly different; tumor size ≤12 cm, a tumor without lymphatic involvement, more than D2 lymphadenectomy, and classification as curability B were favorable prognostic factors. The multivariate analysis revealed that tumor size, lymphadenectomy and curability were independent prognostic factors. In curability B patients, venous involvement was an independent prognostic factor. In curability C patients, both the tumor size and postoperative chemotherapy affected their prognosis. CONCLUSIONS: In patients with curable Stage IV gastric cancer, at least a D2 gastrectomy to reduce the absolute volume of tumor cells, followed by adjuvant chemotherapy, may be essential to improve their prognosis. In incurable cases, aggressive new chemotherapeutic regimens should be the treatment of choice for the prolongation of survival.
Surgery Today 06/2012; · 1.22 Impact Factor
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Takeshi Hanagiri,
Yoshika Nagata,
Shoko Monji, Shinji Shinohara,
Masaru Takenaka,
Yoshiki Shigematsu,
Hidehiko Shimokawa,
Makoto Nakagawa,
Hidetaka Uramoto,
Tomoko So,
Fumihiro Tanaka
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ABSTRACT: BACKGROUND: The incidence of breast cancer has been increasing in Japan over the past three decades, and it is the currently the most common malignancy in Japan. This study investigated the temporal trends of the surgical outcomes in patients with breast cancer. METHODS: We evaluated 543 consecutive patients who underwent breast-cancer resection between 1980 and 2009. The temporal trends in the surgical outcome and clinicopathological features were evaluated separately for the periods covering 1980 to 1989, 1990 to 1999, and 2000 to 2009. RESULTS: The number of patients who underwent resection during these three respective periods were 133, 176, and 234, respectively. All patients were women. The percentage of patients at stages 0 or 1 was 63.2%, 58.5%, and 43.6%, respectively, during the three periods. The mean diameter of tumors in each period was 38, 29, and 30 mm, respectively. The percentage of tumors with positive ER expression was 62.5%, 64.3%, and 69.7%, respectively. In terms of surgical procedures, the use of Halsted's radical mastectomy decreased during each period: from 40.6% of cases to 8.5% and then to 0.4%, while the proportion of breast-conserving therapies increased, from 0% to 12.5%, and finally to 35.9%. The postoperative 10-year survival rates during the three periods were 75.9%, 83.5%, and 84.9%, respectively. The 10-year survival rates of patients with stage II disease during the three periods were 66.2%, 75.7%, and 90.7%, respectively. The prognosis of stage III disease in the three periods also showed a tendency toward improvement, increasing from 37.8% to 64.2%, and finally to 84.5%. CONCLUSION: The survival of patients with stage II and III disease has improved during the past 30 years. Along with the recent advances in drug therapy, the surgical treatment has become less invasive, often because of drug therapy-related modifications.
World Journal of Surgical Oncology 06/2012; 10(1):108. · 1.12 Impact Factor
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Shinji Shinohara,
Takeshi Hanagiri,
Masaru Takenaka,
Soichi Oka,
Yasuhiro Chikaishi,
Yoshiki Shigematsu,
Yoshika Nagata,
Hidehiko Shimokawa,
Makoto Nakagawa,
Hidetaka Uramoto,
Tomoko So,
Fumihiro Tanaka
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ABSTRACT: Endobronchial lipoma is a rare, benign disease. When it causes chronic cough and pneumonia due to obstruction of the central airway, appropriate treatment is required. We herein report 2 cases of endobronchial lipoma successfully treated with a high-frequency electric snare through a flexible bronchoscope. Case 1, an 83-year-old man, visited a nearby hospital because of dyspnea on exertion. Chest computerized tomography revealed a tumor in the right main bronchus. He was referred to our hospital for further examination and treatment. Bronchoscopy showed a polypoid lesion in the right main bronchus. The tumor was resected by high-frequency electric snare through a flexible bronchoscope. Case 2 was an 83-year-old man who was diagnosed with pneumonia by a primary care physician on the basis of findings on chest computerized tomography. Bronchoscopy showed a polypoid lesion at the orifice of the right B6 bronchus, which caused segmental obstructive pneumonia. The tumor was bronchoscopically resected using a high-frequency electric snare and an neodymium-yttrium-aluminum-garnet laser. In both cases, the pathologic diagnosis was endobronchial lipoma.
Journal of bronchology & interventional pulmonology. 01/2012; 19(1):68-71.
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Masaru Takenaka,
Takeshi Hanagiri, Shinji Shinohara,
Taiji Kuwata,
Yasuhiro Chikaishi,
Soich Oka,
Yoshiki Shigematsu,
Yoshika Nagata,
Hidehiko Shimokawa,
Makoto Nakagawa,
Hidetaka Uramoto,
Tomoko So,
Fumihiro Tanaka
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ABSTRACT: The human epidermal growth factor receptor HER-2/neu (HER2) gene is a proto-oncogene involved in the signal transduction pathways leading to cell growth and differentiation. The present study focused on the clinical significance of the expression of HER2 in non-small cell lung cancer (NSCLC).
Consecutive specimens of 159 adenocarcinomas and 77 squamous cell carcinomas, from patients who had been treated by complete resection of NSCLC in our department between 2003 and 2005, were studied. The HER2 expression was evaluated by immunohistochemical staining with score of membranous staining being 0=none, 1=weak, 2=10-30% cells, 3≥30% cells stained.
The staining scores in adenocarcinoma were 0 in 121 patients (76.1%), 1 in 16 (10.0%), 2 in 17 (10.7%), and 3 in 5 patients (3.1%). The HER2 expression scores in squamous cell carcinoma were 0 in 74 patients (96.1%), 1 in 1 (1.2%), 2 in 1 (1.2%), and 3 in 1 patient (1.2%). The postoperative 5-year survival rate of patients with adenocarcinoma according to the expression of HER2 scores 0, 1, 2 and 3 was 75.3%, 77.8%, 76.5% and 20.0%, respectively. Patients with adenocarcinoma with score 3 staining had a significantly unfavorable prognosis compared to those with staining scores of 0-2 (p=0.0216).
HER2 overexpression (score 3) in adenocaricinoma was a significantly unfavorable prognostic factor. Since the number of NSCLC patients with HER2 overexpression was small, further investigations will be necessary to clarify the efficacy of molecular targeted therapy for this subgroup.
Anticancer research 12/2011; 31(12):4631-6. · 1.73 Impact Factor
