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The emotion is an active reaction with being eloquent of the emotions such as the change of the look with the physiological reaction which is strong in the automatic nerves system, the immune system, the endocrine system which occurs with the organolepty which the creature felt.However, the definition of the emotion is ambiguous. It is different roughly every learning field and for it, there is not a strict distinction of the emotion and the feelings. The handling depends on the interval of the research area and the researcher.There seems to be possibility to complicate the discussion of the concerning with anxiety, theamygdala which is the nucleus of the fear and a cerebral limbic system for the ambiguousness of the definition and to make difficult. Therefore, we made a chart with the emotion , feelings and the mood, placing as the differentreaction. In the tunnel of the tube-like of the comparatively gently long lasting mood, the feelings were wavering but supposed that doing of the eloquent of the emotion which is a physiological reaction and an active reaction didn't accompany. On the other hand, it supposed that an emotion was accompanied by the reaction which is physiological which is strong in the automatic nerves system, the immune system, the endocrine system and doing of the eloquent of the emotion physiological strong, deviating from the feeling control by the ventromedial prefrontal cortex. Moreover, it considered about the relation, too, about the amygdala which is the existence like a nucleus of the experience like an emotion and the chronic pain.

Table S3. Correlation between dose-volume histogram parameters and late morbidities of the rectum in the 24 fractions group. This table summarizes the doseâ volume histogram parameters from V10 to V60, D5cc, D2cc, and Dmax according to the grading of rectal morbidity in the 24 fractions group. (DOCX 16 kb)

Table S2. List of patients who developed grade 2 or higher morbidities. Abbreviation: UCC: Uterine cervical carcinoma, UEA: Uterine endometrioid adenocarcinoma. The asterisks indicates the number of patients who were treated with a previous dose constraint of

Table S1. Dose fractions of C-ion RT and the number of patients with morbidities for each prescription dose. The number in brackets indicates the number of patients who were treated with a previous dose constraint of

This study aims to assess the efficacy and toxicity of definitive radiotherapy for early-stage endometrial carcinoma. The correlation between CT-based dosimetric parameters and clinical outcomes is also evaluated. Between 2002 and 2006, 10 medically inoperable patients with T1-2 endometrial carcinoma were treated with radiotherapy alone. A combination of external beam radiotherapy (EBRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT) was used for 9 patients, and one was treated with HDR-ICBT alone. Dose prescription of HDR-ICBT was determined in reference to CT images at brachytherapy, and a total dose of 22–24 Gy in 4 fractions was delivered to the outer perimeter of the uterine corpus. Dose-volume parameters of the gross tumor volume (GTV), clinical target volume (CTV), and organs at risk were assessed retrospectively using the dose-volume histograms derived from the CT image-based treatment planning system. After a median follow-up of 55 months, 9 patients were alive without evidence of recurrence. One patient died from liver cirrhosis 17 months after radiotherapy. Severe acute and late toxicities were not observed in any of the patients. Average minimum dose to 90% of GTV and CTV (D90) was 88.0 and 45.9 GyEQD2, respectively. The minimum dose delivered to 2 cc of the most irradiated volumes of the rectum and sigmoid colon (D2cc) was 78.9 and 65.9 GyEQD2, respectively. These patients developed Grade 1 late complications. In this study, stage I–II endometrial carcinoma was well-controlled locally with minimum late toxicity by radiotherapy alone with HDR-ICBT. 3D image-based brachytherapy may potentially deliver a sufficiently high dose to the whole tumor without significant increase in dose to surrounding normal tissues.

Purpose: Our previous report indicated that carbon ion beam irradiation upregulated immunogenic, underlining the potential clinical application of radioimmunotherapy. The antimetastatic efficacy of a local combination therapy of carbon-ion radiotherapy and immunotherapy was examined using in vivo murine model. Methods and Materials: Tumors of the mouse squamous cell carcinoma (NR-S1) cells inoculated in the leg of C3H/HeMsNrs mice were locally irradiated with a single 6 Gy dosage of carbon ions (290 MeV/nucleon, 6 cm spread-out Bragg peak). Thirty-six hours after irradiation, alpha-galactosylceramide (alpha-GalCer)-pulsed dendritic cells (DCs) were injected into the leg tumor. The effects on distant lung metastases were investigated using pathological observations and immunohistochemistry. Results: The mice in the control group, which were not irradiated and not injected with alpha-GalCerpulsed DCs, had 168 +/- 53.8 metastatic nodules in their lungs at 2 weeks. The lung metastases were significantly decreased in the mouse which received the combination therapy, and the mean number of lung metastatic nodules was 2.6 +/- 1.9 (P = 0.009). In addition, the size of each lung metastasis was significantly decreased in compared to the control group (P = 0.009). Immunohistochemistry showed that ICAM-1, which activates DCs, was highly expressed on the local tumors of the carbon ionirradiated group. The expression of S100A8 in lung tissue, a marker of the lung pre-metastatic phase, was decreased in the combination therapy group. Conclusion: The combination of carbon ion radiotherapy with the injection of alpha-GalCer-pulsed DCs into the primary tumors significantly decreased the number of lung metastases.

BACKGROUND: The authors previously demonstrated that fibroblast growth factor 2 (FGF2) expression levels in tumor cells (FGF2-T) may be an indicator of the efficacy of radiotherapy in patients with cervical cancer (CC). In the current study, this finding was extended in newly enrolled patients and was investigated further in stromal FGF2 (FGF2-S) expression. METHODS: Sixty-nine patients with CC were recruited as a validation set for the immunohistochemical detection of FGF2-T from biopsy samples that were taken before (pretreatment) or 1 week after the initiation of radiotherapy (midtreatment). The authors also investigated the expression of FGF2 in tumor FGF2-S and investigated vascular endothelial growth factor (VEGF), and cluster of differentiation 31 (CD31) (also called platelet endothelial cell adhesion molecule) in these patients and in an additional 35 patients from a previous study. RESULTS: FGF2 expression was detected in tumor cells from all patients and in stromal cells from 87% of patients. FGF2-T was significantly higher in midtreatment samples (P = .0002), and a high ratio of midtreatment/pretreatment FGF2-T was related significantly to a better prognosis (P = .025). Increased VEGF expression after the initiation of radiotherapy was related significantly to positive FGF2-S in pretreatment samples (P = .035); however, it was not related to prognosis or microvessel density detected by CD31 expression. CONCLUSIONS: Radiation causes a response in tumor cells and adjacent normal cells and changes the extracellular matrix environment. In this study, the authors confirmed their previous findings and demonstrated that changes in FGF2-T expression may be used as a marker to monitor the effectiveness of radiotherapy in patients with CC. These findings should improve patient selection for molecular targeted therapies, such as cytokine inhibitors, after standard-of-care treatment. Cancer 2010. © 2010 American Cancer Society.

European Society for Therapeutic Radiology and Oncology 31（ESTRO31）

Purpose:Our previous research suggested carbon-ion (c-ion) irradiation upregulated immunogenicity in irradiated tumor, underlining the potential clinical application of radioimmunotherapy. The anti-metastatic mechanism of this therapy was examined using in vivo murine model. Methods:Local leg tumors were inoculated with squamous cell carcinoma (NR-S1) in C3H mice, or Lewis lung carcinoma (LLC) in C57BL and NKT knockout mice. Local tumors were irradiated with a single dose of 6 Gy of c-ion. Thirty-six hours after irradiation, alpha-GalCer-pulsed dendritic cells (alpha-GalCer-DCs) were injected into the leg tumor. The effects on lung metastasis were investigated by analysis of S100A8, a marker of lung pre-metastatic phase. Results:Local tumors inoculated with NR-S1 or LLC in the leg were spontaneously spread to lung, and formed several metastatic nodules. Metastatic nodules of NR-S1 were decreased in the mice treated with combination therapy. The expression of S100A8 was reduced only in the combination of c-ion and alpha-GalCer-DCs. Conclusion:Our research suggested a possible mechanism that niche status of distant organ might be regulated by local c-ion irradiated tumor with enhanced immunity., 69th Annual Meeting of Japanese Cancer Association

Propose: Irradiation of carbon-ion (C-ion) leads to the formation of severe DNA damage without dependency on the cell cycle phase and oxygen status. However, the molecular mechanisms underlying the therapeutic response to C-ion are not fully understood. In this study, we investigated the molecular pathways induced by C-ion radiotherapy using sequentially taken biopsy samples of cervical cancers to understand the biological mechanism specific to C-ion radiotherapy. Methods: Biopsy specimens were obtained from 60 patients with cervical cancer, before and during fractionated C-ion radiotherapy. C-ion treatment was initiated with a fraction dose of 2.2 GyE and total dose was 71.2- 74.4 GyE. A second biopsy was taken 1 day after the start of radiation. Transcriptome analysis was performed using single-color oligo-microarrays consisting of 44 K human sequences for biopsy samples from 22 patients. Expression values of genes before and during radiotherapy were compared and the statistical analysis was used with the Wilcoxon signed rank test (p < 0.001). The changes of gene expression were confirmed by Real-time PCR analysis, and further immunohistological analysis was performed to confirm the expression and localization of target proteins using newly enrolled 38 patients. Results: Two hundred and twenty genes were identified as C-ion responded genes (CRGs) in cervical cancers under our microarray-analysis conditions. We found three new CRGs in addition to the previously reported ionizing radiation-induced genes such as CDKN1A, BAX, Fas, and DDB2. The p53-target genes such as MDM2, TRIAP1 and GADD45 were also responded to C-ion in the cervical cancers. Comparison of the expression profiles of the human cervical cancers with those of the experimental murine tumors (Imadome et al. Cancer Biol. Ther. 7: 208 – 217, 2008) showed that the genes categorized into the cell-communication and/or the stress-response were commonly involved in both the expression profiles after C-ion irradiation. Conclusions: Genes responded to C-ion irradiation in human cervical cancers were identified. These genes were mainly involved in cell communication or stress response pathways. Our findings may lead to a better understanding the molecular mechanisms underlying the therapeutic response to C-ion., PTCOG 49 (49th Annual Meeting of the Particle Therapy Co-Operative Group)

重粒子線（炭素イオン線）治療は高い局所制御効果を持つ治療法として注目されており、放射線医学総合研究所では1994年の治療開始以来、5000人以上の患者に対して炭素イオン線治療を実施し、その良好な臨床成績は多数報告されている。しかし全身への微小転移（systemic micrometastases）が想定される症例もあり、必ずしも生存率向上に結びつかない場合もある。一方、これまでに当研究グループでは炭素イオン線照射によって種々の腫瘍の遺伝子発現変化が惹起されることを報告してきた。その中で、腫瘍免疫応答に関与した分子群の発現変化に着目し、免疫療法併用を想起した。すなわち、優れた局所効果を有する炭素イオン線に加えて、遠隔転移抑制を目的とした免疫療法を併用する理想的な集学的治療である。現在、マウス転移腫瘍モデルを用いて、aGalCerパルス樹状細胞（DC）と炭素イオン線併用による遠隔転移の抑制効果研究を実施している。本シンポジウムでは、これまでの研究経緯、すなわち、転移モデルの詳細、準備研究結果、更に最新の成果を紹介する。, NIRS-Chiba University G-COE Symposium

Purpose/Objective(s):Malignant melanoma of the female genital organs is a very rare tumor and resistant to conventional photon radiotherapy. We report six cases of female genital malignant melanoma those were well controlled locally by carbon ion radiotherapy (CIRT). \nMaterials/Methods: Between November 2004 and October 2008, six patients with unresectable female genital malignant melanoma were treated with CIRT. Age of the patients ranged from 55 to 80 years (median;69 years). Four patients had previously untreated locally invasive tumors and other two had locally recurrent tumors after surgery and adjuvant chemotherapy. The tumor located in the vagina (4 patients), both the cervix and the vagina (1 patient). Two patients had inguinal lymph node metastasis and two had distant metastases at CIRT. All patients received a total dose of 57.6 gray equivalent (GyE) in 16 fractions over 4 weeks of CIRT. Three patients received chemotherapy using dacarbazine, ACNU, and vincristine after CIRT. \nResults:The follow-up durations after CIRT were from 12 to 23 months (median; 15.5 months). No patient developed severe acute toxicity during CIRT. No late toxicity of greater Grade 2 was experienced, while Grade 1 proctitis was observed in a patient. All tumors completely responded to CIRT. No patient developed in-field recurrence. The three patients without distant metastasis were alive with no evidence of disease for 12-23 months after CIRT. The two patients with distant metastases died from metastatic disease 13 and 18 months after CIRT, respectively. \nConclutions: CIRT achieved favorable local tumor control without developing severe acute and late toxicity in the treatment of unresectable malignant melanoma of the female genital organs., 2009 ASCO Annual Meeting

Purpose Tumor microenvironment possesses extreamly important role for tumor progression and metastasis. Cytokines have autocrine and paracrine functions, and they are also secreted by normal and cancerous cells. Herewith we investigated an indicator for the efficacy of radiotherapy in cervical cancers (CC) using microarray analysis and immunohistochemical analysis. Patients and methods One hundred and four patients with CC were recruited and divided into two groups (research set: n =35, and validation set: n =69). Microarray analysis was performed in research set and further immunohistochemical analysis (IHA) was performed for all patients to detect candidate radioresponsive markers using pre-radiotherapy and mid-radiotherapy biopsy samples, which were taken one week after initiation of radiotherapy. Results FGF2 in tumor cells (FGF2–T) significantly increased in midtreatment samples compared with pretreatment samples in research set of patients, and the ratio change of FGF2-T was significantly related with better prognosis. This evidence was confirmed in validation set. Next using all 104 patimets we found IHA positive FGF2 in stromal cells (FGF2-S) in 85 patients, and the radiotherapy-induced increase of FGF-S in 23 patients. Though positive FGF2-S in pretreatment samples was significantly related with increased expression change of VEGF, it was not related with poor prognosis. Conclusion Radiation causes severing the normal or cancerous associations with adjacent cells and changes the extracellular matrix environment. Therefore, we need to investigate not only pretreatment status of tumors, but also modified tumor structures during fractionated radiotherapy. In this study, we found FGF2-T expression change as a monitoring marker for the effectiveness of radiotherapy, and found the relationship between FGF2-S in pretreatment status and VEGF expression change in a subgroup of patients., 5th International Conference on Tumor Microenvironment: Progression, Therapy & Prevention