ニワトリDT40細胞を用いたチェックポイント関連遺伝子Rad9の放射線感受性に関する検討

取得学位 : 博士（医学）, 学位授与番号 : 医博甲第1579号, 学位授与年月日 : 平成15年3月25日, 学位授与大学 : 金沢大

Effect of daily setup errors on individual dose distribution in conventional radiotherapy: An initial study

金沢大学医薬保健研究域保健学系Recent linear accelerators can perform cone-beam computed tomography to correct setup errors immediately before dose delivery. We calculated the dose distribution with setup errors acquired from cone-beam computed tomography to determine a more realistic and individual effect of setup errors. The differences in dose distribution were analyzed. The setup errors of three patients who were irradiated in the neck, esophagus, and pelvic area were obtained retrospectively. We found that the maximum dose variances for the three cases were 19.9-35.9%. The maximum dose variance points were relatively far from the isocenter. The volume of the 10% dose difference had widths of 1.3-1.85 cm around the beam edges. The V95 and mean doses at the clinical target volume were mostly unchanged. Doses around the beam edges were more varied than those around the isocenter for every case. The dose on the spinal cord located near the beam edges varied by 5-10% compared with the dose of the radiotherapy plan in two of the cases. We demonstrated the individual dose distributions of the cases affected by daily setup errors for all fractions. © 2009 Japanese Society of Radiological Technology and Japan Society of Medical Physics

Cranial nerve deficit caused by skull metastasis of prostate cancer: three Japanese castration-resistant prostate cancer cases

金沢大学附属病院泌尿器科We report 3 Japanese patients with cranial nerve deficit caused by skull metastasis of prostate cancer (PCa). Case 1 was a 75-year-old patient with a chief complaint of diplopia. The cause of diplopia was right oculomotor nerve palsy from the skull metastasis. External beam radiation therapy (EBRT) to the whole brain, 40 Gy in 20 fractions, was performed and the diplopia improved. Case 2 was a 72-year-old patient with a chief complaint of facioplegia. Bone scintigraphy and computed tomography (CT) of the head revealed right occipital bone metastasis of PCa resulting in right facial nerve palsy. EBRT to the right occipital bone, 50 Gy in 25 fractions, with daily oral dexamethasone (DEX) was performed and facioplegia showed complete recovery. At 12 months after onset, the patient was followed-up with no symptoms. Case 3 was a 74-year-old patient with a chief complaint of diplopia. Diffusion-weighted magnetic resonance imaging (MRI) and positron emission tomography (PET) showed right petrous bone metastasis resulting in right abducent nerve palsy. EBRT to the right petrous bone, 44 Gy in 22 fractions, with oral DEX was performed and diplopia showed complete recovery. At 13 months after onset, the patient was followed-up with no symptoms. MRI and PET may detect PCa metastasis in the skull base more clearly than other imaging modalities. EBRT with 40-50 Gy in 20-25 fractions in association with corticosteroid administration may be reasonable treatment of patients with metastatic PCa who develop cranial nerve dysfunction. © 2010 Japan Society of Clinical Oncology

Impact of pitch angle setup error and setup error correction on dose distribution in volumetric modulated arc therapy for prostate cancer

In volumetric modulated arc therapy (VMAT) for prostate cancer, a positional and rotational error correction is performed according to the position and angle of the prostate. The correction often involves body leaning, and there is concern regarding variation in the dose distribution. Our purpose in this study was to evaluate the impact of body pitch rotation on the dose distribution regarding VMAT. Treatment plans were obtained retrospectively from eight patients with prostate cancer. The body in the computed tomography images for the original VMAT plan was shifted to create VMAT plans with virtual pitch angle errors of ±1.5° and ±3°. Dose distributions for the tilted plans were recalculated with use of the same beam arrangement as that used for the original VMAT plan. The mean value of the maximum dose differences in the dose distributions between the original VMAT plan and the tilted plans was 2.98 ± 0.96 %. The value of the homogeneity index for the planning target volume (PTV) had an increasing trend according to the pitch angle error, and the values of the D95 for the PTV and D2ml, V50, V60, and V70 for the rectum had decreasing trends (p < 0.05). However, there was no correlation between differences in these indexes and the maximum dose difference. The pitch angle error caused by body leaning had little effect on the dose distribution; in contrast, the pitch angle correction reduced the effects of organ displacement and improved these indexes. Thus, the pitch angle setup error in VMAT for prostate cancer should be corrected. © 2016 Japanese Society of Radiological Technology and Japan Society of Medical PhysicsEmbargo Perios 12 month

The J domain of Tpr2 regulates its interaction with the proapoptotic and cell-cycle checkpoint protein, Rad9

金沢大学がん研究所Human Rad9 is a key cell-cycle checkpoint protein that is postulated to function in the early phase of cell-cycle checkpoint control through complex formation with Rad1 and Hus1. Rad9 is also thought to be involved in controlling apoptosis through its interaction with Bcl-2. To explore the biochemical functions of Rad9 in these cellular control mechanisms, we performed two-hybrid screening and identified Tetratricopeptide repeat protein 2 (Tpr2) as a novel Rad9-binding protein. We found that Tpr2 binds not only to Rad9, but also to Radl and Hus1, through its N-terminal tetratricopeptide repeat region, as assessed by in vivo and in vitro binding assays. However, the in vivo and in vitro interactions of Tpr2 with Rad9 were greatly enhanced by the deletion of its C-terminal J domain or by a point mutation in the conserved HPD motif in the J domain, though the binding of Tpr2 to Rad1 and Hus1 was not influenced by these J-domain mutations. We further found: (1) Rad9 transiently dissociates from Tpr2 following heat-shock or UV treatments, but the mutation of the J domain abrogates this transient dissociation of the Tpr2/Rad9 complex; and (2) the J domain of Tpr2 modulates the cellular localization of both Tpr2 itself and Rad9. These results indicate that the J domain of Tpr2 plays a criticai role in the regulation of both physical and functional interactions between Tpr2 and Rad9. © 2001 Academic Press

前立腺癌に対する小線源治療併用強度変調放射線治療における適切な臓器線量制約の確立

金沢大学附属病院本研究では、中高リスク前立腺癌に対する小線源治療・強度変調放射線治療（IMRT）併用療法における適切な臓器線量制約を明らかにすることを目的として、同治療を施行した症例について各臓器の照射線量と有害事象出現について検討した。小線源治療およびIMRTの各々において、尿道・直腸・膀胱・小腸といった危険臓器の評価指標が一定の基準以内であれば、急性及び晩期の有害事象発現頻度は低く、重篤な障害を生じることなく安全に治療可能であることを示した。The purpose of the study was to clarify the appropriate dose constraints of the critical organs in the combination of brachytherapy and intensity-modulated radiation therapy for intermediate/high risk prostate cancer. We examined the dose of each critical organ in the treatment planning of both treatment and the frequency of the adverse events. We showed that this combination therapy was safe without serious adverse event if satisfying the proposed dose constraints for the critical organ (urethra, rectum, bladder and bowel) in each of brachytherapy and IMRT.研究課題/領域番号:24791284, 研究期間(年度):2012-04-01 - 2016-03-3