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3. Long-term survival for advanced esophageal cancer patients with an esophago-bronchial fistula can be achieved by timely multimodality therapy

Author

Yoshida, Takahiro, Tangoku, Akira, Furukita, Yoshihito, Nishino, Takeshi, Takechi, Hirokazu, Kawakami, Yukikiyo, Morishita, Atsushi, Morimoto, Masami, Fujiwara, Satoshi, Inoue, Seiya, Minato, Takuya, Goto, Masakazu, Yamamoto, Yota, Yuasa, Yasuhiro, Yamai, Hiromichi, Seike, Junichi, and Miyoshi, Takanori

Published
2015
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4. GHSRmethylation‑dependent expression of a variant ligand and receptor of the ghrelin system induces thymoma tumorigenesis

Author

Tegshee, Bilguun, primary, Kondo, Kazuya, additional, Soejima, Shiho, additional, Muguruma, Kyoka, additional, Tsuboi, Mitsuhiro, additional, Kajiura, Koichiro, additional, Kawakami, Yukikiyo, additional, Kawakita, Naoya, additional, Toba, Hiroaki, additional, Yoshida, Mitsuteru, additional, Takizawa, Hiromitsu, additional, and Tangoku, Akira, additional

Published
2021
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5. Indocyanine green fluorescence imaging for resection of pulmonary metastasis of hepatocellular carcinoma

Author

Kawakita, Naoya, Takizawa, Hiromitsu, Sawada, Toru, Matsumoto, Daisuke, Tsuboi, Mitsuhiro, Toba, Hiroaki, Yoshida, Mitsuteru, Kawakami, Yukikiyo, Kondo, Kazuya, and Tangoku, Akira

Subjects
indocyanine green (ICG), marking, fluorescence, Hepatocellular carcinoma (HCC), neoplasms, pulmonary metastasis
Abstract

Background: Indocyanine green (ICG) accumulates in hepatocellular carcinoma (HCC), and tumor fluorescence can be observed under irradiation with near infrared light (NIR). This study investigated the clinical utility of ICG fluorescence imaging during resection of pulmonary metastases of HCC. Methods: From April 2010 to June 2018, six patients with suspected pulmonary metastasis of HCC were enrolled prospectively. Prior to surgery, all patients underwent the ICG hepatic function test following intravenous administration of ICG (0.5 mg/kg body weight). During surgery, metastatic HCC was identified by observation of ICG fluorescence, allowing assessment of the surgical margin. Tumor fluorescence was also evaluated on cut sections. Results: A total of 11 metastatic HCCs were resected in six patients at nine operations. Eight lesions were removed by wedge resection and 3 lesions were managed by lobectomy. During surgery, tumor fluorescence could be confirmed through the visceral pleura in 6 out of 7 lesions treated by wedge resection, while NIR irradiation was difficult for 1 lesion. For these 6 lesions, the median distance from the tumor to the visceral pleura and the median surgical margin were 0 mm (range, 0–2 mm) and 14 mm (range, 11–17 mm), respectively. When cut sections were examined, all tumors emitted fluorescence. All lesions were histologically confirmed to be metastatic HCC. Conclusions: In patients with pulmonary metastasis of HCC, ICG fluorescence imaging is useful for identifying the tumor and securing its margin when the lesion is peripheral and wedge resection is planned.

Published
2019

6. Diagnosis of visceral pleural invasion using confocal laser endomicroscopy during lung cancer surgery

Author

Sawada, Toru, primary, Takizawa, Hiromitsu, additional, Aoyama, Mariko, additional, Kawakita, Naoya, additional, Miyamoto, Naoki, additional, Sakamoto, Shinichi, additional, Takashima, Mika, additional, Matsumoto, Daisuke, additional, Toba, Hiroaki, additional, Kawakami, Yukikiyo, additional, Yoshida, Mitsuteru, additional, Kondo, Kazuya, additional, and Tangoku, Akira, additional

Published
2021
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9. Hypervascularized bronchial arteries as a risk factor for intraoperative bleeding and prolonged surgery

Author

Takizawa, Hiromitsu, Miyamoto, Naoki, Sakamoto, Shinichi, Takashima, Mika, Matsumoto, Daisuke, Kawakita, Naoya, Toba, Hiroaki, Kawakami, Yukikiyo, Yoshida, Mitsuteru, Kondo, Kazuya, Tangoku, Akira, Takizawa, Hiromitsu, Miyamoto, Naoki, Sakamoto, Shinichi, Takashima, Mika, Matsumoto, Daisuke, Kawakita, Naoya, Toba, Hiroaki, Kawakami, Yukikiyo, Yoshida, Mitsuteru, Kondo, Kazuya, and Tangoku, Akira

Abstract

Background: The present study investigated whether highly vascularized bronchial arteries affect the intraoperative blood loss and the operative time of video-assisted thoracic surgery (VATS) lobectomy for patients with non-small cell lung cancer. Methods: We retrospectively collected data on consecutive pathological stage I to IIIA non-small cell lung cancer patients who underwent VATS lobectomy with systematic lymph node dissection between January 2017 and December 2019. Patients were divided into the following two groups according to bronchial artery diameters on preoperative enhanced contrast computed tomography (CT) findings: ≤2 and >2 mm groups. Results: Among the 175 patients enrolled, risk factors for intraoperative blood loss >50 mL were being male (P=0.005), a history of smoking (P=0.01), percent forced expiratory volume in 1 s (FEV1.0%) <70% (P=0.012), squamous cell carcinoma (P=0.049), and a bronchial artery diameter >2.0 mm (P<0.001) in the unadjusted analysis, and a bronchial artery diameter >2.0 mm (P<0.001) in the multivariable analysis. Risk factors for an operative time >200 min were being male (P<0.001), a history of smoking (P=0.007), FEV1.0% <70% (P=0.011), squamous cell carcinoma (P=0.046), a bronchial artery diameter >2.0 mm (P<0.001), and experience of surgeon <10 years (P=0.011) in the unadjusted analysis, and being male (P=0.047), a bronchial artery diameter >2.0 mm (P=0.024), and experience of surgeon <10 years (P=0.047) in the multivariable analysis. Conclusions: Bronchial artery diameter was the most important risk factor of intraoperative bleeding and prolonged operative time during VATS lobectomy.

Published
2021

10. Can computed tomography differentiate adenocarcinoma in situ from minimally invasive adenocarcinoma?

Author

Yoshida, Mitsuteru, Yuasa, Masao, Ogawa, Hirohisa, Miyamoto, Naoki, Kawakami, Yukikiyo, Kondo, Kazuya, Tangoku, Akira, Yoshida, Mitsuteru, Yuasa, Masao, Ogawa, Hirohisa, Miyamoto, Naoki, Kawakami, Yukikiyo, Kondo, Kazuya, and Tangoku, Akira

Abstract

Background: Given the subtle pathological signs of adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA), effective differentiation between the two entities is crucial. However, it is difficult to predict these conditions using preoperative computed tomography (CT) imaging. In this study, we investigated whether histological diagnosis of AIS and MIA using quantitative three-dimensional CT imaging analysis could be predicted. Methods: We retrospectively analyzed the images and histopathological findings of patients with lung cancer who were diagnosed with AIS or MIA between January 2017 and June 2018. We used Synapse Vincent (v. 4.3) (Fujifilm) software to analyze the CT attenuation values and performed a histogram analysis. Results: There were 22 patients with AIS and 22 with MIA. The ground-glass nodule (GGN) rate was significantly higher in patients with AIS (p < 0.001), whereas the solid volume (p < 0.001) and solid rate (p = 0.001) were significantly higher in those with MIA. The mean (p = 0.002) and maximum (p = 0.025) CT values were significantly higher in patients with MIA. The 25th, 50th, 75th, and 97.5th percentiles (all p < 0.05) for the CT values were significantly higher in patients with MIA. Conclusions: We demonstrated that quantitative analysis of 3D-CT imaging data using software can help distinguish AIS from MIA. These analyses are useful for guiding decision-making in the surgical management of early lung cancer, as well as subsequent follow-up.

Published
2021

12. GAD1 expression and its methylation as indicators of malignant behavior in thymic epithelial tumors

Author

Soejima, Shiho, primary, Kondo, Kazuya, additional, Tsuboi, Mitsuhiro, additional, Muguruma, Kyoka, additional, Tegshee, Bilguun, additional, Kawakami, Yukikiyo, additional, Kajiura, Koichiro, additional, Kawakita, Naoya, additional, Toba, Hiroaki, additional, Yoshida, Mitsuteru, additional, Takizawa, Hiromitsu, additional, and Tangoku, Akira, additional

Published
2021
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13. Long-term outcomes of sentinel node identification using indocyanine green in patients with lung cancer

Author

Kawakami, Yukikiyo, Kondo, Kazuya, Kawakita, Naoya, Matsuoka, Hisashi, Toba, Hiroaki, Takizawa, Hiromitsu, Yoshida, Mitsuteru, Tangoku, Akira, Kawakami, Yukikiyo, Kondo, Kazuya, Kawakita, Naoya, Matsuoka, Hisashi, Toba, Hiroaki, Takizawa, Hiromitsu, Yoshida, Mitsuteru, and Tangoku, Akira

Abstract

Background: Sentinel node (SN) biopsy is used in the management of numerous cancers to avoid unnecessary lymphadenectomy. This was a clinical exploration/feasibility study of a novel identification technique for SN biopsy using indocyanine green (ICG) fluorescence imaging during lung cancer surgery. Methods: SN biopsy using ICG was performed on 22 patients who had cT1 or T2N0M0 lung cancer. ICG was injected just around the primary tumor. The fluorescence imaging system enabled visualization of the lymphatic vessels draining from the primary tumor toward the lymph nodes. Fluorescently labeled nodes were dissected, and patients were followed-up for prognosis and recurrence to confirm the pattern of lymph node metastasis after surgery. Results: SNs were successfully identified in 16 (72.7%) of 22 patients. A total of 13 of 16 patients had pathological N0 and three had SN metastasis. The median follow-up time was 92.7 months. Only one patient had no SN metastasis at the postoperative pathological examination and lymph node metastasis during the follow-up period. The accuracy rate was 93.8% (15/16) and the false-negative rate was 7.7% (1/13). Conclusions: SNs were identified by ICG fluorescence imaging, and this technique during lung cancer surgery had good identification and accuracy rates throughout the follow-up period.

Published
2020

14. Cone‐beam computed tomography versus computed tomography‐guided ultrathin bronchoscopic diagnosis for peripheral pulmonary lesions: A propensity score‐matched analysis

Author

Kawakita, Naoya, primary, Takizawa, Hiromitsu, additional, Toba, Hiroaki, additional, Sakamoto, Shinichi, additional, Miyamoto, Naoki, additional, Matsumoto, Daisuke, additional, Takashima, Mika, additional, Tsuboi, Mitsuhiro, additional, Yoshida, Mitsuteru, additional, Kawakami, Yukikiyo, additional, Kondo, Kazuya, additional, and Tangoku, Akira, additional

Published
2021
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16. EXPRESSION OF GHRELIN SYSTEM CONSTITUENTS IN THYMIC EPITHELIAL TUMORS

Author

Tegshee, Bilguun, Kondo, Kazuya, Soejima, Shiho, Muguruma, Kyoka, Tsuboi, Mitsuhiro, Kajiura, Koichiro, Kawakami, Yukikiyo, Kawakita, Naoya, Toba, Hiroaki, Yoshida, Mitsuteru, Takizawa, Hiromitsu, and Tangoku, Akira

Subjects
ghrelin, digestive, oral, and skin physiology, In‑1 ghrelin, GHSR, thymoma, thymic epithelial tumors, thymic carcinoma
Abstract

Our previous study reported that the DNA methylation of growth hormone secretagogue receptor (GHSR) was significantly higher in thymoma or thymic carcinoma (TC) than in normal thymic tissue samples. Thymic epithelial tumors (TETs) with higher GHSR DNA methylation were associated with significantly worse prognosis than those with lower levels of DNA methylation. Diversified components of the ghrelin‑GHSR axis may exert opposing effects in cancer progression, depending on the cancer type in question. However, the precise function of the axis remains unclear. In the present study, the mRNA expression of five key components of the ghrelin system [native ligand ghrelin, variant ligand In‑1 ghrelin, native receptor GHSR1a, variant receptor GHSR1b and acylation enzyme ghrelin O‑acyltransferase (GOAT)] were examined in 58 TET samples by reverse transcription‑quantitative PCR, and protein expression of GHSR1a and GHSR1b was assessed in 20 TETs using immunohistochemistry. The results revealed that In‑1 ghrelin, GHSR1b (variant forms) and GOAT were more strongly expressed in thymoma compared with thymic‑adjacent tissue. By contrast, no significant differences were observed in the expression of ghrelin and GHSR1a (native forms) between thymoma and thymic tissue. The mRNA expression of In‑1 ghrelin and GHSR1b (variant forms) was positively associated with GHSR methylation in thymoma tissue samples. However, a relationship was not found between ghrelin, GHSR1a or GOAT expression (native forms) and GHSR methylation in thymoma. Immunohistochemical analysis revealed that mRNA expression of GHSR1a and GHSR1b generally correlated with expression of the corresponding protein, and that the expression of GHSR1b was increased in advanced‑stage TETs. These results indicate that the DNA methylation of GHSR is associated with a shift from native expression (ghrelin and GHSR1a) to variant expression (In‑1 ghrelin and GHSR1b), which induces the tumorigenesis of thymoma, but not TC.

Published
2021

20. GAD1 EXPRESSION AND DNA METHYLATION IN THYMIC EPITHELIAL TUMORS

Author

Soejima, Shiho, Kondo, Kazuya, Tsuboi, Mitsuhiro, Muguruma, Kyoka, Tegshee, Bilguun, Kawakami, Yukikiyo, Kajiura, Koichiro, Kawakita, Naoya, Toba, Hiroaki, Yoshida, Mitsuteru, Takizawa, Hiromitsu, and Tangoku, Akira

Subjects
DNA methylation, paradoxical expression, GAD1, hemic and lymphatic diseases, Thymic carcinoma (TC), thymoma, poor prognosis
Abstract

Thymic epithelial tumors (TETs) comprise thymomas and thymic carcinoma (TC). TC has more aggressive features and a poorer prognosis than thymomas. Genetic and epigenetic alterations in thymomas and TC have been investigated in an attempt to identify novel target molecules for TC. In the present study, genome‑wide screening was performed on aberrantly methylated CpG islands in thymomas and TC, and the glutamate decarboxylase 1 gene (GAD1) was identified as the 4th significantly hypermethylated CpG island in TC compared with thymomas. GAD1 catalyzes the production of γ‑aminobutyric acid from L‑glutamic acid. GAD1 expression is abundant in the brain but rare in other tissues, including the thymus. A total of 73 thymomas and 17 TC tissues were obtained from 90 patients who underwent surgery or biopsy at Tokushima University Hospital between 1990 and 2017. DNA methylation was examined by bisulfite pyrosequencing, and the mRNA and protein expression levels of GAD1 were analyzed using reverse transcription‑quantitative PCR and immunohistochemistry, respectively. The DNA methylation levels of GAD1 were significantly higher in TC tissues than in the normal thymus and thymoma tissues, and GAD1 methylation exhibited high sensitivity and specificity for discriminating between TC and thymoma. The mRNA and protein expression levels of GAD1 were significantly higher in TC tissues than in thymomas. Patients with TET with high GAD1 DNA hypermethylation and high mRNA and protein expression levels had significantly shorter relapse‑free survival rates than those with low levels. In conclusion, significantly more epigenetic alterations were observed in TC tissues compared with in thymomas, which may contribute to the clinical features and prognosis of patients.

Published
2021

22. Fetal tissue for mouse lung regeneration

Author

Uyama, Koh, Sakiyama, Shoji, Yoshida, Mitsuteru, Kenzaki, Koichiro, Toba, Hiroaki, Kawakami, Yukikiyo, Okumura, Kazumasa, Takizawa, Hiromitsu, Kondo, Kazuya, and Tangoku, Akira

Subjects
lung regeneration, Pallid mouse, COPD, respiratory system, pulmonary emphysema, fetal tissue, respiratory tract diseases
Abstract

The mortality and morbidity of chronic obstructive pulmonary disease are high. However, no radical therapy has been developed to date. The purpose of this study was to evaluate whether fetal mouse lung tissue can grow and differentiate in the emphysematous lung. Fetal lung tissue from green fluorescent protein C57BL/6 mice at 16 days’ gestation was used as donor material. Twelve-month-old pallid mice were used as recipients. Donor lungs were cut into small pieces and implanted into the recipient left lung by performing thoracotomy under anesthesia. The recipient mice were sacrificed at day 7, 14, and 28 after implantation and used for histological examination. Well-developed spontaneous pulmonary emphysema was seen in 12-month-old pallid mice. Smooth and continuous connection between implanted fetal lung tissue and recipient lung was recognized. Air space expansion and donor tissue differentiation were observed over time. We could clearly distinguish the border zones between injected tissue and native tissue by the green fluorescence of grafts. Fetal mouse lung fragments survived and differentiated in the emphysematous lung of pallid mice. Implantation of fetal lung tissue in pallid mice might lead to further lung regeneration research from the perspective of respiratory and exercise function.

Published
2016

23. DNA methylation of GHSR, GNG4, HOXD9 and SALL3 is a common epigenetic alteration in thymic carcinoma

Author

Kishibuchi, Reina, primary, Kondo, Kazuya, additional, Soejima, Shiho, additional, Tsuboi, Mitsuhiro, additional, Kajiura, Koichiro, additional, Kawakami, Yukikiyo, additional, Kawakita, Naoya, additional, Sawada, Toru, additional, Toba, Hiroaki, additional, Yoshida, Mitsuteru, additional, Takizawa, Hiromitsu, additional, and Tangoku, Akira, additional

Published
2019
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26. Transbronchial Biopsy Using an Ultrathin Bronchoscope Guided by Cone-Beam Computed Tomography and Virtual Bronchoscopic Navigation in the Diagnosis of Pulmonary Nodules

Author

Ali, Eman A.A., primary, Takizawa, Hiromitsu, additional, Kawakita, Naoya, additional, Sawada, Toru, additional, Tsuboi, Mitsuhiro, additional, Toba, Hiroaki, additional, Takashima, Mika, additional, Matsumoto, Daisuke, additional, Yoshida, Mitsuteru, additional, Kawakami, Yukikiyo, additional, Kondo, Kazuya, additional, Khairy El-Badrawy, Mohammad, additional, and Tangoku, Akira, additional

Published
2019
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27. A feasibility study of postoperative adjuvant chemotherapy with fluoropyrimidine S-1 in patients with stage II-IIIA non-small cell lung cancer

Author

Tsuboi, Mitsuhiro, Kondo, Kazuya, Takizawa, Hiromitsu, Kawakita, Naoaya, Sawada, Toru, Toba, Hiroaki, Kawakami, Yukikiyo, Yoshida, Mitsuteru, Ishikura, Hisashi, Kimura, Suguru, Tangoku, Akira, Tsuboi, Mitsuhiro, Kondo, Kazuya, Takizawa, Hiromitsu, Kawakita, Naoaya, Sawada, Toru, Toba, Hiroaki, Kawakami, Yukikiyo, Yoshida, Mitsuteru, Ishikura, Hisashi, Kimura, Suguru, and Tangoku, Akira

Abstract

Background : Adjuvant chemotherapy with uracil tegafur (UFT) improved survival among patients with completely resected stage I lung adenocarcinoma. S-1, an oral dihydropyrimidine dehydrogenase (DPD)- inhibitory 5-fluorouracil, is a more potent DPD inhibitor than UFT ; therefore, we hypothesized that postoperative adjuvant chemotherapy with S-1 would be effective for advanced non-small cell lung cancer (NSCLC). We conducted a feasibility study of S-1 as postoperative adjuvant chemotherapy in patients with curatively resected pathological stage II and IIIA NSCLC. Methods : Adjuvant chemotherapy consisted of 9 courses (4-week administration, 2-week withdrawal) of S-1 at 80-120 mg/body per day. Twenty-four patients with completely resected NSCLC were enrolled in this study from November 2007 through December 2010. The primary endpoint was the rate of completion of the scheduled adjuvant chemotherapy. The secondary endpoints were safety, overall survival, and relapse-free survival. Results : Five patients were censored because of disease recurrence. The planned 9 courses of S-1 were administered to completion in 8 patients. Twelve patients completed more than 70% of the planned courses. Grade 3 adverse reactions, such as elevated total bilirubin (4.2%) and pneumonitis (4.2%), were observed, but there were no Grade 4 adverse reactions. Patients who completed more than 70% of the 9 courses demonstrated better overall survival than those who completed less than 70%. Conclusion : Postoperative administration of S-1 may be possible with few severe adverse events as adjuvant chemotherapy for patients with curatively resected pathological stage II-IIIA NSCLC.

Published
2018

28. Long‐term outcomes of sentinel node identification using indocyanine green in patients with lung cancer.

Author

Kawakami, Yukikiyo, Kondo, Kazuya, Kawakita, Naoya, Matsuoka, Hisashi, Toba, Hiroaki, Takizawa, Hiromitsu, Yoshida, Mitsuteru, and Tangoku, Akira

Subjects
*CANCER relapse, *CLINICAL trials, *DIAGNOSTIC errors, *DIAGNOSTIC imaging, *LUNG tumors, *METASTASIS, *PATIENTS, *SURGERY, *PREDICTIVE tests, *SENTINEL lymph nodes, *INDOLE compounds, *DESCRIPTIVE statistics, *FLUORESCENT dyes, *SENTINEL lymph node biopsy
Abstract

Background: Sentinel node (SN) biopsy is used in the management of numerous cancers to avoid unnecessary lymphadenectomy. This was a clinical exploration/feasibility study of a novel identification technique for SN biopsy using indocyanine green (ICG) fluorescence imaging during lung cancer surgery. Methods: SN biopsy using ICG was performed on 22 patients who had cT1 or T2N0M0 lung cancer. ICG was injected just around the primary tumor. The fluorescence imaging system enabled visualization of the lymphatic vessels draining from the primary tumor toward the lymph nodes. Fluorescently labeled nodes were dissected, and patients were followed‐up for prognosis and recurrence to confirm the pattern of lymph node metastasis after surgery. Results: SNs were successfully identified in 16 (72.7%) of 22 patients. A total of 13 of 16 patients had pathological N0 and three had SN metastasis. The median follow‐up time was 92.7 months. Only one patient had no SN metastasis at the postoperative pathological examination and lymph node metastasis during the follow‐up period. The accuracy rate was 93.8% (15/16) and the false‐negative rate was 7.7% (1/13). Conclusions: SNs were identified by ICG fluorescence imaging, and this technique during lung cancer surgery had good identification and accuracy rates throughout the follow‐up period. Key points: Significant findings of the study: We attempted to identify sentinel lymph nodes by indocyanine green in lung cancer surgery. The identification rate was 72.7%. The accuracy rate was 100% immediately after surgery, and 93.8% after follow‐up. What this study adds: Sentinel node biopsy by indocyanine green may be useful for lymph node dissection during lung cancer surgery to avoid unnecessary lymphadenectomy. [ABSTRACT FROM AUTHOR]

Published
2021
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31. A feasibility study of postoperative adjuvant chemotherapy with fluoropyrimidine S‐1 in patients with stage II‐IIIA non‐small cell lung cancer

Author

Tsuboi, Mitsuhiro, primary, Kondo, Kazuya, additional, Takizawa, Hiromitsu, additional, Kawakita, Naoya, additional, Sawada, Toru, additional, Toba, Hiroaki, additional, Kawakami, Yukikiyo, additional, Yoshida, Mitsuteru, additional, Ishikura, Hisashi, additional, Kimura, Suguru, additional, and Tangoku, Akira, additional

Published
2018
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32. Autofluorescence for the diagnosis of visceral pleural invasion in non-small-cell lung cancer

Author

Takizawa, Hiromitsu, primary, Kondo, Kazuya, additional, Kawakita, Naoya, additional, Tsuboi, Mitsuhiro, additional, Toba, Hiroaki, additional, Kajiura, Koichiro, additional, Kawakami, Yukikiyo, additional, Sakiyama, Shoji, additional, Tangoku, Akira, additional, Morishita, Atsushi, additional, Nakagawa, Yasushi, additional, and Hirose, Toshiyuki, additional

Published
2017
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33. Frequent silencing of RASSF1A by DNA methylation in thymic neuroendocrine tumours

Author

Kajiura, Koichiro, Takizawa, Hiromitsu, Morimoto, Yuki, Masuda, Kiyoshi, Tsuboi, Mitsuhiro, Kishibuchi, Reina, Wusiman, Nuliamina, Sawada, Toru, Kawakita, Naoya, Toba, Hiroaki, Yoshida, Mitsuteru, Kawakami, Yukikiyo, Naruto, Takuya, Imoto, Issei, Tangoku, Akira, Kondo, Kazuya, Kajiura, Koichiro, Takizawa, Hiromitsu, Morimoto, Yuki, Masuda, Kiyoshi, Tsuboi, Mitsuhiro, Kishibuchi, Reina, Wusiman, Nuliamina, Sawada, Toru, Kawakita, Naoya, Toba, Hiroaki, Yoshida, Mitsuteru, Kawakami, Yukikiyo, Naruto, Takuya, Imoto, Issei, Tangoku, Akira, and Kondo, Kazuya

Abstract

Objectives: Aberrant methylation of promoter CpG islands (CGIs) of tumour suppressor genes is a common epigenetic mechanism underlying cancer pathogenesis. The methylation patterns of thymic tumours have not been studied in detail since such tumours are rare. Herein, we sought to identify genes that could serve as epigenetic targets for thymic neuroendocrine tumour (NET) therapy. Materials and Methods: Genome-wide screening for aberrantly methylated CGIs was performed in three NET samples, seven thymic carcinoma (TC) samples, and eight type-B3 thymoma samples. The methylation status of thymic epithelial tumours (TETs) samples was validated by pyrosequencing in a larger cohort. The expression status was analysed by quantitative polymerase chain reaction (PCR) and immunohistochemistry. Results: We identified a CGI on a novel gene, RASSF1A, which was strongly hypermethylated in NET, but not in thymic carcinoma or B3 thymoma. RASSF1A was identified as a candidate gene statistically and bibliographically, as it showed frequent CGI hypermethylation in NET by genome-wide screening. Pyrosequencing confirmed significant hypermethylation of a RASSF1A CGI in NET. Low-grade NET tissue was more strongly methylated than high-grade NET. Quantitative PCR and immunohistochemical staining revealed that RASSF1A mRNA and protein expression levels were negatively regulated by DNA methylation. Conclusions: RASSF1A is a tumour suppressor gene epigenetically dysregulated in NET. Aberrant methylation of RASSF1A has been reported in various tumours, but this is the first report of RASSF1A hypermethylation in TETs. RASSF1A may represent an epigenetic therapeutic target in thymic NET.

Published
2017

34. Frequent silencing of RASSF1A by DNA methylation in thymic neuroendocrine tumours

Author

Kajiura, Koichiro, primary, Takizawa, Hiromitsu, additional, Morimoto, Yuki, additional, Masuda, Kiyoshi, additional, Tsuboi, Mitsuhiro, additional, Kishibuchi, Reina, additional, Wusiman, Nuliamina, additional, Sawada, Toru, additional, Kawakita, Naoya, additional, Toba, Hiroaki, additional, Yoshida, Mitsuteru, additional, Kawakami, Yukikiyo, additional, Naruto, Takuya, additional, Imoto, Issei, additional, Tangoku, Akira, additional, and Kondo, Kazuya, additional

Published
2017
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35. Perioperative oral management can prevent postoperative pneumonia after lung cancer surgery

Author

Nishino, Takeshi, primary, Takizawa, Hiromitsu, additional, Sawada, Toru, additional, Kawakita, Naoya, additional, Tsuboi, Mitsuhiro, additional, Kajiura, Koichiro, additional, Toba, Hiroaki, additional, Yoshida, Mitsuteru, additional, Kawakami, Yukikiyo, additional, Kondo, Kazuya, additional, Yamamura, Yoshiko, additional, and Azuma, Masayuki, additional

Published
2017
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45. Intraoperative diagnosis of pleural invasion of lung cancer patients: Evaluation of accuracy

Author

Takizawa, Hiromitsu, primary, Tsuboi, Mitsuhiro, additional, Kajiura, Koichiro, additional, Toba, Hiroaki, additional, Nakagawa, Yasushi, additional, Kawakami, Yukikiyo, additional, Yoshida, Mitsuteru, additional, Sakiyama, Shoji, additional, Kondo, Kazuya, additional, Morishita, Atsushi, additional, Kawakita, Naoya, additional, and Hirose, Toshiyuki, additional

Published
2015
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46. Long-term survival for advanced esophageal cancer patients with an esophago-bronchial fistula can be achieved by timely multimodality therapy

Author

Yoshida, Takahiro, primary, Tangoku, Akira, additional, Furukita, Yoshihito, additional, Nishino, Takeshi, additional, Takechi, Hirokazu, additional, Kawakami, Yukikiyo, additional, Morishita, Atsushi, additional, Morimoto, Masami, additional, Fujiwara, Satoshi, additional, Inoue, Seiya, additional, Minato, Takuya, additional, Goto, Masakazu, additional, Yamamoto, Yota, additional, Yuasa, Yasuhiro, additional, Yamai, Hiromichi, additional, Seike, Junichi, additional, and Miyoshi, Takanori, additional

Published
2014
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47. Non-invasive monitoring of anticancer effects of cisplatin on lung cancer in an orthotopic SCID mouse model using [18F] FDG PET-CT

Author

MOKHTAR, MOHAMED, primary, KONDO, KAZUYA, additional, TAKIZAWA, HIROMITSU, additional, OHTANI, TAMAKI, additional, OTSUKA, HIDEKI, additional, KUBO, HITOSHI, additional, KAJIURA, KOICHIRO, additional, NAKAGAWA, YASUSHI, additional, KAWAKAMI, YUKIKIYO, additional, YOSHIDA, MITSUTERU, additional, FUJINO, HARUHIKO, additional, SAKIYAMA, SHOJI, additional, and TANGOKU, AKIRA, additional

Published
2014
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49. The effect of nutritional support on the immune function in the acute postoperative period after esophageal cancer surgery : total parenteral nutrition versus enteral nutrition

Author

Seike, Junichi, Tangoku, Akira, Yuasa, Yasuhiro, Okitsu, Hiroshi, Kawakami, Yukikiyo, Sumitomo, Masayuki, Seike, Junichi, Tangoku, Akira, Yuasa, Yasuhiro, Okitsu, Hiroshi, Kawakami, Yukikiyo, and Sumitomo, Masayuki

Abstract

Background : Enteral nutrition (EN) is now used more frequently than total parenteral nutrition (TPN) for nutritional support after resection for esophageal cancer. But consensus regarding which type of nutrition should be used does not exist. We studied the effect of TPN and EN on patients’ nutritional status and immune function in the immediate postoperative period after esophageal cancer resection. Methods : We enrolled 30 patients (27 men and 3 women) who underwent subtotal esophagectomy. The patients were randomly assigned to TPN or EN group. Either TPN or EN was begun on postoperative day 1. On postoperative days 1, 3, and 7, three endpoints were measured : albumin, C-reactive protein, and Th1/Th2 balance. Results : All patients completed the study. Anastomotic leaks occurred in 6 patients in the TPN group and 7 patients in the EN group. Albumin, Th1/Th2 balance, and C-reactive protein did not differ between the groups. Th1/Th2 balance was not different regardless of the preoperative treatment or complications. Conclusions. No differences in immune function, nutritional state, or inflammatory response were seen between patients supported with TPN and those supported with EN. The results of our study suggest that perioperative nutritional support can be safely performed either with TPN or EN.

Published
2011

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