Details of a Researcher - SOMEYA Masanori

Papers - SOMEYA Masanori

Division display 41 - 60 of about 85 ／ All the affair displays >>

Phase 2 Study of Neoadjuvant Treatment of Sequential S-1-Based Concurrent Chemoradiation Therapy Followed by Systemic Chemotherapy with Gemcitabine for Borderline Resectable Pancreatic Adenocarcinoma (HOPS-BR 01).

Tsuyoshi Hayashi, Toru Nakamura, Yasutoshi Kimura, Makoto Yoshida, Masanori Someya, Hiroshi Kawakami, Yusuke Sakuhara, Norio Katoh, Kuniyuki Takahashi, Yoshiyasu Ambo, Katsutoshi Miura, Masayo Motoya, Eiichi Tanaka, Katsuhiko Murakawa, Takumi Yamabuki, Hajime Yamazaki, Akio Katanuma, Satoshi Hirano

International journal of radiation oncology, biology, physics ( Elsevier {BV} ) 105 ( 3 ) 606 - 617 2019.11 [Refereed] [International journal]

PURPOSE: Preoperative treatment is recommended for borderline resectable pancreatic ductal adenocarcinoma. However, the standard treatment has not yet been determined. We conducted a multicenter phase 2 study to investigate the efficacy of neoadjuvant treatment of sequential chemoradiation followed by chemotherapy. METHODS AND MATERIALS: All enrolled patients were treated by preoperative chemoradiation (a total dose of 50.4 Gy in 28 fractions and orally administered S-1 at 80 mg/m2 on the day of irradiation) followed by chemotherapy (administration of gemcitabine at 1000 mg/m2/dose on days 1, 8, and 15 in 3 cycles of 4 weeks) and attempted curative resection. The primary outcome was an R0 resection rate among patients who completed preoperative treatment and pancreatectomy. The threshold of the R0 resection rate was defined as 74% based on a previous study of up-front surgery. RESULTS: Forty-five patients were included. Twenty-one patients could not undergo pancreatectomy because of progressive diseases (n = 14), adverse events (n = 5), or consent withdrawal (n = 2), and 4 patients underwent additional resection after dropping out. The resection rates were 53.3% and 62.2% in the per-protocol set (PPS) and full analysis set (FAS) populations, respectively. The R0 resection rates were 95.8% (95% confidence interval, 78.9%-99.9%) and 96.4% (81.7%-99.9%) in the PPS and FAS populations, respectively. The median overall survival and progression-free survival of all the included patients were 17.3 and 10.5 months, respectively. The median survival time of the patients with pancreatectomy was significantly longer than that of the patients without pancreatectomy in the PPS (27.9 vs 12.3 months; P = .001) and FAS populations (32.2 vs 11.8 months; P < .001). CONCLUSIONS: This study revealed that a long duration of preoperative treatment of sequential chemoradiation followed by systemic chemotherapy provides a high rate of R0 resection and sufficient survival time in patients undergoing pancreatectomy.

Influence of XRCC4 expression by breast cancer cells on ipsilateral recurrence after breast-conserving therapy.

Mio Kitagawa, Masanori Someya, Tomokazu Hasegawa, Toshihiko Mikami, Kazuaki Asaishi, Tadashi Hasegawa, Yoshihisa Matsumoto, Goro Kutomi, Ichiro Takemasa, Koh-Ichi Sakata

Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] 195 ( 7 ) 648 - 658 2019.07 [Refereed] [International journal]

BACKGROUND: We examined the expression of nonhomologous end-joining (NHEJ) proteins by breast cancer cells in patients with or without ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy. We also investigated whether there was a difference of NHEJ-related protein expression by tumor cells between two types of IBTR, i.e., true recurrence (TR) with regrowth from the tumor bed or development of a new primary tumor (NP). PATIENTS AND METHODS: The original cohort comprised 560 breast cancer patients who received breast-conserving therapy between February 1995 and March 2006, including 520 patients without IBTR and 40 patients with IBTR. Propensity score matching was employed to select 40 trios (120 patients) consisting of 1 patient with IBTR and 2 patients without IBTR. Immunohistochemical examination of proteins related to NHEJ was performed in surgical specimens. RESULTS: The 40 patients with IBTR included 22 patients who developed TR and 18 who had NP. The 15-year overall survival rate was 85.9% for patients with NP and 95.5% for those with TR, while it was 96.5% for patients without IBTR. Patients with high XRCC4 expression in tumor cells had significantly higher IBTR rates than those with low XRCC4 expression (P < 0.001). The frequency of TR was significantly higher in patients with high expression of XRCC4 than in those with low XRCC4 expression (p < 0.001). XRCC4 expression by tumor cells was not significantly related to development of NP. CONCLUSION: IBTR due to TR may be related to low radiosensitivity of tumor cells, possibly related to high XRCC4 expression.

Histopathological differences of experimental aneurysms treated with bare platinum, fibered, and bioactive coils.

Yoko Usami, Naoki Hirokawa, Masato Saitoh, Hiroki Okuda, Masanori Someya, Tadashi Hasegawa, Yasunari Takakuwa, Koh-Ichi Sakata

Minimally invasive therapy & allied technologies : MITAT : official journal of the Society for Minimally Invasive Therapy 28 ( 3 ) 172 - 177 2019.06 [Refereed] [International journal]

PURPOSE: To evaluate the histopathological features of experimental aneurysms embolized with bare platinum, fibered, and bioactive coils. MATERIAL AND METHODS: Twelve experimental aneurysms were constructed in three swine. The aneurysms were divided into four groups and were embolized using a bare platinum coil alone (P group, n = 2), a bioactive coil alone (B group, n = 2), a combination of fibered and bare platinum coils (F/P group, n = 4) and a combination of fibered and bioactive coils (F/B group, n = 4). Histopathological data for all aneurysms recorded at 63 days were analyzed in terms of neointima formation, fibrosis, foreign-body giant-cell infiltration, and organization. RESULTS: Fibrosis was significantly greater in group B compared with that in group F/P (p = .02). Inflammation with foreign-body giant-cell infiltration was significantly greater in groups F/P and F/B compared with that in groups P and B (p = .007). CONCLUSION: The present study revealed that the embolic effect of fibered coils was not a thrombus but instead was a foreign-body response in the chronic phase.

Efficacy of combined radiotherapy and anti-programmed death 1 therapy in acral and mucosal melanoma.

Junji Kato, Tokimasa Hida, Masanori Someya, Sayuri Sato, Masahide Sawada, Kohei Horimoto, Mao Fujioka, Tomoyuki Minowa, Yoshiyuki Matsui, Takaaki Tsuchiya, Mio Kitagawa, Kensei Nakata, Koh-Ichi Sakata, Toshihiko Torigoe, Hisashi Uhara

The Journal of dermatology 46 ( 4 ) 328 - 333 2019.04 [Refereed] [International journal]

Some studies showed that clinical response to immune check point inhibitors is lower in acral and mucosal melanoma than in cutaneous melanoma. Although the synergistic effect of radiotherapy (RT) and ipilimumab has been reported in patients with brain metastasis, the efficacy of combined RT and anti-programmed death 1 (PD-1) therapy for acral and mucosal melanoma is unclear. The present study aimed to evaluate the efficacy of combined RT and anti-PD-1 therapy for acral and mucosal melanoma. We retrospectively analyzed patients with acral or mucosal melanoma who were treated with anti-PD-1 and RT at Sapporo Medical University Hospital. In 10 patients (acral, 3; mucosal, 7), the response rate (RR) and the disease control rate (DCR) were 40% and 60%, respectively. As regards mucosal melanoma, four of the seven patients had achieved complete response + partial response, and three had progressive disease (RR = 57.1%). Meanwhile, two of the three patients with acral melanoma had stable disease and one had progressive disease (RR and DCR were 0% and 66.6%, respectively). Except for the patients treated with palliative RT for bone metastasis in the present study, the RR was 50% (4/8 patients), and the DCR was 75% (6/8 patients). Vitiligo developed after RT in five (50%) patients at a median duration of 2 months after RT. The clinical response and the high occurrence of vitiligo suggest that the combination of RT and anti-PD-1 therapy could be effective in some patients with mucosal melanoma.

Successful rechallenge with nivolumab therapy after radiotherapy in mucosal melanoma.

Junji Kato, Tokimasa Hida, Kohei Horimoto, Sayuri Sato, Keiju Kobayashi, Masahide Sawada, Mao Fujioka, Takaaki Tsuchiya, Masanori Someya, Hisashi Uhara

The Journal of dermatology 46 ( 2 ) e72-e73 - e73 2019.02 [Refereed] [International journal]

当院で腔内照射を施行した子宮頸癌の線量解析(DVH Analysis of Intracavitary Brachytherapy for Uterine Cervical Cancer)

Someya Masanori, Hasegawa Tomokazu, Tsuchiya Takaaki, Kitagawa Mio, Gocho Toshio, Fukushima Yuuki, Takada Yu, Miura Katsutoshi, Hori Masakazu, Sakata Koh-ichi

日本医学放射線学会学術集会抄録集 ( (公社)日本医学放射線学会 ) 78回 S264 - S264 2019.02

Influence of PD-L1 expression in immune cells on the response to radiation therapy in patients with oropharyngeal squamous cell carcinoma.

Yuki Fukushima, Masanori Someya, Kensei Nakata, Masakazu Hori, Mio Kitagawa, Tomokazu Hasegawa, Takaaki Tsuchiya, Toshio Gocho, Hikaru Ikeda, Yoshihiko Hirohashi, Toshihiko Torigoe, Shintaro Sugita, Tadashi Hasegawa, Tetsuo Himi, Koh-Ichi Sakata

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 129 ( 2 ) 409 - 414 2018.11 [Refereed] [International journal]

BACKGROUND AND PURPOSE: To investigate influences of proteins involved with tumor immunity on outcomes of radiotherapy for oropharyngeal squamous cell carcinoma (OPSCC). MATERIAL AND METHODS: We performed immunohistochemical staining to examine expressions of p16 and proteins involved with tumor immunity in 92 OPSCC patients treated with radiotherapy. RESULTS: Patients with abundant infiltrating CD8-positive cells had the significantly better overall survival (OS) rate than patients with fewer CD8-positive cells (p = 0.026). Patients with higher PD-L1 expression in tumor cells (TC 1-3) had a better outcome than those with low PD-L1 expression in tumor cells (TC 0) for both OS (p = 0.019) and progression-free survival (PFS) rate (p = 0.032). Patients with high PD-L1 expression in infiltrating immune cells (IC 3) showed significantly better OS (p = 0.009) and PFS (p = 0.011) than those with low PD-L1 expression (IC 0-2). Patients with p16-negative and IC 3 showed similar OS to patients with p16-positive and IC 0-2. P16-positive tumors had a significantly higher CD8-positive cell infiltration and PD-L1 expression in tumor cells than p16-negative tumors. CONCLUSIONS: In addition to tumor p16 expression, PD-L1 expression in TC and IC can be useful for predicting the response of OPSCC to radiotherapy.

Differential diagnosis between intraductal papillary mucinous neoplasm with an associated invasive carcinoma and pancreatic ductal adenocarcinoma on ultrasonography: the utility of echo intensity and contrast enhancement.

Masato Saito, Naoki Hirokawa, Yoko Usami, Masanori Someya, Koh-Ichi Sakata

Ultrasonography (Seoul, Korea) ( Korean Society of Ultrasound in Medicine ) 36 ( 3 ) 260 - 269 2017.07 [Refereed] [International journal]

PURPOSE: The aim of this study was to investigate the utility of echo intensity and contrast enhancement in the differential diagnosis between intraductal papillary mucinous neoplasm with an associated invasive carcinoma (IPMN-IC) and pancreatic ductal adenocarcinoma (PDAC) on ultrasonography. METHODS: This study included eight and 37 patients who had pathologically confirmed IPMN-IC and PDAC, respectively, and were enrolled for a comparative analysis of the sonographic features of the tumors. In the quantitative echo intensity evaluation, the two groups were compared with respect to the difference between the tumor intensity and the pancreatic intensity (TI-PI) and between the tumor intensity and the vascular intensity (TI-VI). In the quantitative contrast enhancement evaluation, the increase in echo intensity (ΔTI) and increase in echo intensity per unit of time (slope) were compared between the groups. The echo intensity and contrast enhancement were also compared between the two groups in patients with T3-T4 disease. In addition, the correlations of the histological type, tumor size, stromal type, and T factor with echogenicity and contrast enhancement were analyzed. RESULTS: IPMN-IC had significantly greater echo intensity and contrast enhancement than PDAC (TI-PI, P=0.004; TI-VI, P=0.001; ΔTI, P=0.012; slope, P=0.002). In T3-T4 disease, IPMN-IC also showed greater echo intensity and faster enhancement than PDAC. Echo intensity and contrast enhancement were correlated with histological type (TI-PI, P=0.003; TI-VI, P<0.001; ΔTI, P=0.007; slope, P<0.001). CONCLUSION: IPMN-IC and PDAC can be differentiated by the quantitative evaluation of echo intensity and contrast enhancement.

Influence of XRCC4 expression in esophageal cancer cells on the response to radiotherapy.

Masakazu Hori, Masanori Someya, Yoshihisa Matsumoto, Kensei Nakata, Mio Kitagawa, Tomokazu Hasegawa, Takaaki Tsuchiya, Yuki Fukushima, Toshio Gocho, Yasushi Sato, Hiroyuki Ohnuma, Junji Kato, Shintaro Sugita, Tadashi Hasegawa, Koh-Ichi Sakata

Medical molecular morphology 50 ( 1 ) 25 - 33 2017.03 [Refereed] [Domestic journal]

DNA double-strand break (DSB) is one of the most serious forms of damage induced by ionizing irradiation and is mainly repaired by the non-homologous end joining (NHEJ) repair. Immunohistochemical analysis of proteins involved in NHEJ, such as XRCC4 (X-ray repair cross-complementing protein 4), Ku86 and DNA-PKcs (DNA-dependent protein kinase, catalytic subunits), may be useful for predicting tumor radiosensitivity. We examined 92 patients with esophageal squamous cell carcinoma (ECSS) who were treated by radiotherapy between 1999 and 2008. Immunohistochemical examination of tumor tissue for Ki-67 and DSB-related proteins, including XRCC4, Ku86, and DNA-PKcs, was performed using pretreatment biopsy specimens. Low expression of XRCC4 was detected in 31 of 92 examined samples (33.7 %). The 5-year overall survival (OS) rate was 67.7 % in the low expression group and 31.0 % in the high expression group (P = 0.00). Multivariate analysis confirmed that advanced T-stage (HR 3.24, P = 0.01), radiation dose less than 66 Gy (HR 2.23, P = 0.02), absence of systemic chemotherapy (HR 2.59, P = 0.05), and high expression of XRCC4 (HR 12.0, P = 0.02) were independent prognostic factors for predicting poor OS. Other DSB-related proteins and Ki-67 were not predictive factors. XRCC4 expression might have an influence on results of radiotherapy for patients with ESCC.

Expression of Ku70 predicts results of radiotherapy in prostate cancer.

Tomokazu Hasegawa, Masanori Someya, Masakazu Hori, Yoshihisa Matsumoto, Kensei Nakata, Masanori Nojima, Mio Kitagawa, Takaaki Tsuchiya, Naoya Masumori, Tadashi Hasegawa, Koh-Ichi Sakata

Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] 193 ( 1 ) 29 - 37 2017.01 [Refereed] [International journal]

BACKGROUND AND PURPOSE: Therapeutic strategy for prostate cancer is decided according to T stage, Gleason score, and prostate-specific antigen (PSA) level. These clinical factors are not accurate enough to predict individual risk of local failure of prostate cancer after radiotherapy. Parameters involved with radiosensitivity are required to improve the predictive capability for local relapse. PATIENTS AND METHODS: We analyzed 58 patients with localized adenocarcinoma of the prostate between August 2007 and October 2010 treated with 76 Gy of intensity-modulated radiotherapy (IMRT) as a discovery cohort and 42 patients between March 2001 and May 2007 treated with three-dimensional conformal radiotherapy (3D-CRT) as a validation cohort. Immunohistochemical examination for proteins involved in nonhomologous end-joining was performed using biopsy specimens. RESULTS: Ku70 expression was not correlated with various clinical parameters, such as the Gleason score and D'amico risk classification, indicating that Ku70 expression was an independent prognostic factor. The predictive value for PSA relapse was markedly improved after the combination of Gleason score and Ku70 expression, as compared with Gleason score alone. In patients treated with radiotherapy and androgen deprivation therapy (ADT), no relapses were observed in patients with Gleason score ≤7 or low Ku70 expression. In contrast, patients with Gleason score ≥8 and high Ku70 expression had high PSA relapse rates. In the validation cohort, similar results were obtained. CONCLUSION: Treatment with 76 Gy and ADT can be effective for patients with Gleason score ≤7 or low Ku70 expression, but is not enough for patients with Gleason score ≥8 and high Ku70 expression and, thus, require other treatment approaches.

Influence of Ku86 and XRCC4 expression in uterine cervical cancer on the response to preoperative radiotherapy.

Yu Takada, Masanori Someya, Yoshihisa Matsumoto, Masaaki Satoh, Kensei Nakata, Masakazu Hori, Masato Saito, Naoki Hirokawa, Kunihiko Tateoka, Mizue Teramoto, Tsuyoshi Saito, Tadashi Hasegawa, Koh-Ichi Sakata

Medical molecular morphology ( SPRINGER JAPAN KK ) 49 ( 4 ) 210 - 216 2016.12 [Refereed] [Domestic journal]

DNA double-strand breaks (DSB) are severe damages induced by ionizing radiation. Non-homologous end joining (NHEJ) is a major mechanism for repairing DSB. Immunohistochemical analysis of proteins involved in NHEJ, such as Ku86 and XRCC4 (X-ray repair cross-complementing protein 4) may be useful for predicting tumor radiosensitivity. We examined the relationship between expression of DSB-related proteins in biopsy specimens of uterine cervical cancer and the pathological effect of 40 Gy of preoperative radiotherapy. 119 patients with uterine cervical cancer were treated between 2000 and 2011. Pathological effects of preoperative radiotherapy were classified by examining hysterectomy specimens. Patients with complete response (pCR) had a significantly better overall 5-year survival rate than those without pCR (96.3 vs. 76.9 %, P = 0.02). The pCR rate was significantly higher in patients with low Ku86 and XRCC4 expression than in other patients (47.4 vs. 21.3 %, P = 0.04). Logistic regression analysis also demonstrated that low Ku86 and XRCC4 expression was a significant predictor of pCR (P = 0.03). Patients with high Ku86 and XRCC4 expression had a significantly lower 5-year metastasis-free rate than others (79.3 vs. 93.5 %, P = 0.02). Proteins involved with NHEJ might have an influence on results of radiotherapy for uterine cervical cancer.

A Phase 1/2 Study of Definitive Chemoradiation Therapy Using Docetaxel, Nedaplatin, and 5-Fluorouracil (DNF-R) for Esophageal Cancer.

Hiroyuki Ohnuma, Yasushi Sato, Masahiro Hirakawa, Yutaka Okagawa, Takahiro Osuga, Tsuyoshi Hayashi, Tsutomu Sato, Koji Miyanishi, Masayoshi Kobune, Rishu Takimoto, Tamotsu Sagawa, Masakazu Hori, Masanori Someya, Kensei Nakata, Koh-Ichi Sakata, Tetsuji Takayama, Junji Kato

International journal of radiation oncology, biology, physics 93 ( 2 ) 382 - 90 2015.10 [Refereed] [International journal]

PURPOSE: Patient survival in esophageal cancer (EC) remains poor. The purpose of this study was to investigate a regimen of definitive chemoradiation therapy (CRT) that exerts good local control of EC. We performed a phase 1/2 study to assess the safety and efficacy of CRT with docetaxel, nedaplatin, and 5-fluorouracil (DNF-R). METHODS AND MATERIALS: Eligible patients presented with stage IB to IV EC. Patients received 2 cycles of docetaxel (20, 30, or 40 mg/m(2)) and nedaplatin (50 mg/m(2)) on days 1 and 8 and a continuous infusion of 5-fluorouracil (400 mg/m(2)/day) on days 1 to 5 and 8 to 12, every 5 weeks, with concurrent radiation therapy (59.4 Gy/33 fractions). The recommended dose (RD) was determined using a 3 + 3 design. RESULTS: In the phase 1 study, the dose-limiting toxicities were neutropenia and thrombocytopenia. The RD of docetaxel was determined to be 20 mg/m(2). In the phase 2 study, grade 3 to 4 acute toxicities included neutropenia (42.8%), febrile neutropenia (7.14%), thrombocytopenia (17.9%), and esophagitis (21.4%). Grade 3 to 4 late radiation toxicity included esophagostenosis (10.7%). The complete response rate was 82.1% (95% confidence interval: 67.9-96.3%). Both the median progression-free survival and overall survival were 41.2 months. CONCLUSIONS: DNF-R showed good tolerability and strong antitumor activity, suggesting that it is a potentially effective therapeutic regimen for EC.

Analysis of Prostate Deformation during a Course of Radiation Therapy for Prostate Cancer.

Takuya Nakazawa, Kunihiko Tateoka, Yuichi Saito, Tadanori Abe, Masaki Yano, Yuji Yaegashi, Hirokazu Narimatsu, Kazunori Fujimoto, Akihiro Nakata, Kensei Nakata, Masanori Someya, Masakazu Hori, Masato Hareyama, Koichi Sakata

PloS one 10 ( 6 ) e0131822 2015 [Refereed] [International journal]

PURPOSE: Accurate analysis of the correlation between deformation of the prostate and displacement of its center of gravity (CoG) is important for efficient radiation therapy for prostate cancer. In this study, we addressed this problem by introducing a new analysis approach. METHOD: A planning computed tomography (CT) scan and 7 repeat cone-beam CT scans during the course of treatment were obtained for 19 prostate cancer patients who underwent three-dimensional conformal radiation therapy. A single observer contoured the prostate gland only. To evaluate the local deformation of the prostate, it was divided into 12 manually defined segments. Prostate deformation was calculated using in-house developed software. The correlation between the displacement of the CoG and the local deformation of the prostate was evaluated using multiple regression analysis. RESULTS: The mean value and standard deviation (SD) of the prostate deformation were 0.6 mm and 1.7 mm, respectively. For the majority of the patients, the local SD of the deformation was slightly lager in the superior and inferior segments. Multiple regression analysis revealed that the anterior-posterior displacement of the CoG of the prostate had a highly significant correlation with the deformations in the middle-anterior (p < 0.01) and middle-posterior (p < 0.01) segments of the prostate surface (R2 = 0.84). However, there was no significant correlation between the displacement of the CoG and the deformation of the prostate surface in other segments. CONCLUSION: Anterior-posterior displacement of the CoG of the prostate is highly correlated with deformation in its middle-anterior and posterior segments. In the radiation therapy for prostate cancer, it is necessary to optimize the internal margin for every position of the prostate measured using image-guided radiation therapy.

Phase I study of oral S-1 and concurrent radiotherapy in patients with head and neck cancer.

Kensei Nakata, Koh-Ichi Sakata, Masanori Someya, Katsutoshi Miura, Junichi Hayashi, Masakazu Hori, Masaru Takagi, Tetsuo Himi, Atsushi Kondo, Masato Hareyama

Journal of radiation research 54 ( 4 ) 679 - 83 2013.07 [Refereed] [International journal]

This study investigated the maximum tolerated dose (MTD) of S-1 with concurrent radiotherapy in patients with head and neck cancer, based on the frequency of dose-limiting toxicities (DLT). S-1 was administered orally at escalating doses from 40 mg/m(2) b.i.d. on the days of delivering radiotherapy, which was given at a total dose of 64-70 Gy in 32-35 fractions over 6-7 weeks. A total of 12 patients (3 patients at 40 mg/m(2), 6 patients at 60 mg/m(2), and 3 patients at 80 mg/m(2)) were enrolled in this trial. At the dose of 80 mg/m(2), two of the three patients developed DLT (Grade 3 anorexia and rhabdomyolysis) due to S-1, so the MTD was determined to be 80 mg/m(2). Among the 12 enrolled patients, 9 (75%) showed a complete response and 3 (25%) showed a partial response. The overall response rate was 100%. The recommended dose of S-1 with concurrent radiotherapy is 60 mg/m(2).

Analysis and results of Ku and XRCC4 expression in hypopharyngeal cancer tissues treated with chemoradiotherapy.

Jyunichi Hayashi, Koh-Ichi Sakata, Masanori Someya, Yoshihisa Matsumoto, Masaaki Satoh, Kensei Nakata, Masakazu Hori, Masaru Takagi, Atsushi Kondoh, Tetsuo Himi, Masato Hareyama

Oncology letters 4 ( 1 ) 151 - 155 2012.07 [Refereed] [International journal]

DNA double-strand break (DSB) is one of the most serious forms of damage induced by ionizing irradiation. Non-homologous end-joining (NHEJ) is a key mechanism of DNA DSB repair. The immunohistochemical analysis of proteins involved in NHEJ may have potential as a predictive assay for tumor radiosensitivity. We examined the correlation between the expression of proteins involved in DNA DSB in biopsy specimens and the results of chemoradiotherapy in hypopharyngeal cancers. Fifty-seven patients with previously untreated squamous cell carcinoma of the hypopharynx were treated between March 2002 and December 2009. Most patients (75%) had stage III or IV disease. The chemotherapy consisted of cisplatin plus 5FU or S-1. A tumor dose of 50 Gy was usually administered to the primary tumor and regional lymph nodes. Doses of 10-20 Gy were usually added to the primary tumor with reduced fields after 50 Gy. The 5-year disease-free survival rate was 100% for patients in stage I, 90% in stage II, 64% in stage III and 50% in stage IV. In stages I-III, patients with a lower expression of Ku70 or XRCC4 tended to have better locoregional control. These results indicated that a lower expression of Ku70 or XRCC4 may be correlated with higher radiosensitivity. Two patients had distant metastasis alone, of which one had 0% expression of Ku70 and the other had 0% expression of Ku86. The absence of Ku70 or Ku86 expression indicates low DNA-PK activity. Low DNA-PK activity due to a low expression of Ku may result in the genetic alteration of cancer cells, leading to a higher tendency of distant metastasis. This finding suggests that proteins involved in NHEJ may have an impact on the treatment results of chemoradiotherapy in hypopharyngeal cancer.

The combination of olaparib and camptothecin for effective radiosensitization.

Katsutoshi Miura, Koh-ichi Sakata, Masanori Someya, Yoshihisa Matsumoto, Hideki Matsumoto, Akihisa Takahashi, Masato Hareyama

Radiation oncology (London, England) 7 62 - 62 2012.04 [Refereed] [International journal]

BACKGROUND: Poly (ADP-ribose) polymerase-1 (PARP-1) is a key enzyme involved in the repair of radiation-induced single-strand DNA breaks. PARP inhibitors such as olaparib (KU-0059436, AZD-2281) enhance tumor sensitivity to radiation and to topoisomerase I inhibitors like camptothecin (CPT). Olaparib is an orally bioavailable inhibitor of PARP-1 and PARP-2 that has been tested in multiple clinical trials. The purpose of this study was to investigate the characteristics of the sensitizing effect of olaparib for radiation and CPT in order to support clinical application of this agent. METHODS: DLD-1 cells (a human colorectal cancer cell line) and H1299 cells (a non-small cell lung cancer cell line) with differences of p53 gene status were used. The survival of these cells was determined by clonogenic assay after treatment with drugs and X-ray irradiation. The γH2AX focus formation assay was performed to examine the influence of olaparib on induction and repair of double-stranded DNA breaks after exposure to radiation or CPT. RESULTS: A radiosensitizing effect of olaparib was seen even at 0.01 μM. Its radiosensitizing effect after exposure for 2 h was similar to that after 24 h. H1299 cells with depletion or mutation of p53 were more radioresistant than H1299 cells with wild-type p53. However, similar enhancement of radiosensitization by olaparib was observed with all of the tested cell lines regardless of the p53 status. Olaparib also sensitized cells to CPT. This sensitizing effect was seen at low concentrations of olaparib such as 0.01 μM, and its sensitizing effect was the same at both 0.01 μM and 1 μM. The combination of olaparib and CPT had a stronger radiosensitizing effect. The results of the γH2AX focus assay corresponded with the clonogenic assay findings. CONCLUSION: Olaparib enhanced sensitivity to radiation and CPT at low concentrations and after relatively short exposure times such as 2 h. The radiosensitizing effect of olaprib was not dependent on the p53 status of tumor cells. These characteristics could be advantageous for clinical radiotherapy since tumor cells may be exposed to low concentrations of olaparib and/or may have different levels of p53 mutation. The combination of olaparib and CPT had a stronger radiosensitizing effect, indicating that combining a PARP inihibitor with a topoiomerase I inhibitor could be promising for clinical radiosensitization.

The combination of hyperthermia or chemotherapy with gimeracil for effective radiosensitization

M. Takagi, K. Sakata, M. Someya, Y. Matsumoto, H. Tauchi, M. Hareyama, M. Fukushima

STRAHLENTHERAPIE UND ONKOLOGIE ( URBAN & VOGEL ) 188 ( 3 ) 255 - 261 2012.03 [Refereed]

Purpose. 5-chloro-2,4-dihydroxypyridine (gimeracil) is a component of the oral fluoropyrimidine derivative S-1. Gimeracil was originally added to S-1 to yield prolonged 5-fluorouracil (5-FU) concentrations in serum and tumor tissues by inhibiting dihydropyrimidine dehydrogenase, which degrades 5-FU. We previously demonstrated that gimeracil enhances the efficacy of radiotherapy through the suppression of homologous recombination (HR) in DNA double strand repair. The goal of this paper was to examine the effects of gimeracil on the sensitivity of anticancer drugs and hyperthermia in order to obtain effective radiosensitization. Materials and methods. Various cell lines, including DLD 1 (human colon carcinoma cells) and cells deficient in HR or nonhomologous end-joining (NHEJ), were used in clonogenic assays. The survival of these cells after various treatments (e.g., drug treatment, heat treatment, and radiation) was determined based on their colony-forming ability. Results. Gimeracil enhanced cell-killing effects of camptothecin (CPT), 5-FU, and hydroxyurea. Gimeracil sensitized effects of CPT or 5-FU to cells deficient in HR or NHEJ to a similar extent as in other cells (DLD1 and a parent cell), indicating that its sensitizing mechanisms may be different from inhibition of HR or NHEJ. Combination of gimeracil and CPT or 5-FU sensitized radiation more effectively than each modality alone. Gimeracil also enhanced heat sensitivity at 42 degrees C or more. The degree of heat sensitization with gimeracil increased as the temperature increased, and the combination of gimeracil and heat-sensitized radiation was more effective than each modality alone. Conclusion. Gimeracil enhanced sensitivity of CPT, 5-FU, and hyperthermia. Combination of these modalities sensitized radiation more efficiently than each modality alone.

A clinical survey of hospitalization with radical radiotherapy for early stage glottic laryngeal cancer:

Kensei Nakata, Koichi Sakata, Masaru Takagi, Masanori Someya, Atsushi Kondo, Tetsuo Himi, Masato Hareyama

Japanese Journal of Head and Neck Cancer 38 ( 3 ) 315 - 317 2012

We retrospectively investigated the relationship between the duration of hospitalization and the regimen of definitive radiotherapy for patients with early stage glottic laryngeal cancer in our institution during the period from 2006 to 2011. The total number of hospitalized patients who underwent radiation therapy in this period was 45 (43 men, 2 women). Twenty-one patients had been treated by accelerated hyperfractionation (AHF), 19 patients by conventional fractionation (CF, and 5 patients by accelerated fractionation (AF). Average duration of radiation therapy was 23.4, 48.5, 38.4 days respectively and average duration of hospitalization was 37.3, 57.4, and 49 days respectively. Our data suggest that the AHF method can shorten the period of hospitalization by 20 days on average compared to the CF method.

Gimeracil, an inhibitor of dihydropyrimidine dehydrogenase, inhibits the early step in homologous recombination.

Koh-Ichi Sakata, Masanori Someya, Yoshihisa Matsumoto, Hiroshi Tauchi, Masahiro Kai, Minoru Toyota, Masaru Takagi, Masato Hareyama, Masakazu Fukushima

Cancer science 102 ( 9 ) 1712 - 6 2011.09 [Refereed] [International journal]

Gimeracil (5-chloro-2, 4-dihydroxypyridine) is an inhibitor of dihydropyrimidine dehydrogenase (DPYD), which degrades pyrimidine including 5-fluorouracil in the blood. Gimeracil was originally added to an oral fluoropyrimidine derivative S-1 to yield prolonged 5-fluorouracil concentrations in serum and tumor tissues. We have already reported that gimeracil had radiosensitizing effects by partially inhibiting homologous recombination (HR) in the repair of DNA double strand breaks. We investigated the mechanisms of gimeracil radiosensitization. Comet assay and radiation-induced focus formation of various kinds of proteins involved in HR was carried out. siRNA for DPYD were transfected to HeLa cells to investigate the target protein for radiosensitization with gimeracil. SCneo assay was carried out to examine whether DPYD depletion by siRNA inhibited HR repair of DNA double strand breaks. Tail moments in neutral comet assay increased in gimeracil-treated cells. Gimeracil restrained the formation of foci of Rad51 and replication protein A (RPA), whereas it increased the number of foci of Nbs1, Mre11, Rad50, and FancD2. When HeLa cells were transfected with the DPYD siRNA before irradiation, the cells became more radiosensitive. The degree of radiosensitization by transfection of DPYD siRNA was similar to that of gimeracil. Gimeracil did not sensitize DPYD-depleted cells. Depletion of DPYD by siRNA significantly reduced the frequency of neopositive clones in SCneo assay. Gimeracil partially inhibits the early step in HR. It was found that DPYD is the target protein for radiosensitization by gimeracil. The inhibitors of DPYD, such as gimeracil, could enhance the efficacy of radiotherapy through partial suppression of HR-mediated DNA repair.

Gene expression associated with DNA-dependent protein kinase activity under normoxia, hypoxia, and reoxygenation.

Tadashi Tsuchimoto, Koh-ichi Sakata, Masanori Someya, Hiroyuki Yamamoto, Ryoichi Hirayama, Yoshihisa Matsumoto, Yoshiya Furusawa, Masato Hareyama

Journal of radiation research 52 ( 4 ) 464 - 71 2011 [Refereed] [International journal]

　 PREV - NEXT 　

1
2
3
4
5

To the head of this page.▲