IL-12 and IL-18 Induction and Subsequent NKT Activation Effects of the Japanese Botanical Medicine Juzentaihoto

In this study, we first measured some cytokine concentrations in the serum of patients treated with Juzentaihoto (JTT). Of the cytokines measured interleukin (IL) -18 was the most prominently up-regulated cytokine in the serum of patients under long term JTT administration. We next evaluated the effects of JTT in mice, focusing especially on natural killer T (NKT) cell induction. Mice fed JTT were compared to control group ones. After sacrifice, the liver was fixed, embedded and stained. Transmission electron microscope (TEM) observations were performed. Although the mice receiving the herbal medicine had same appearance, their livers were infiltrated with massive mononuclear cells, some of which were aggregated to form clusters. Immunohistochemical staining revealed that there was abundant cytokine expression of IL-12 and IL-18 in the liver of JTT treated mice. To clarify what the key molecules that induce immunological restoration with JTT might be, we next examined in vitro lymphocyte cultures. Mononuclear cells isolated and prepared from healthy volunteers were cultured with and without JTT. Within 24 hours, JTT induced the IL-12 and IL-18 production and later (72 hours) induction of interferon (IFN)-gamma. Oral administration of JTT may induce the expression of IL-12 in the early stage, and IL-18 in the chronic stage, followed by NKT induction. Their activation, following immunological restoration could contribute to anti-tumor effects

Neutralization of hepatitis B virus with vaccine-escape mutations by hepatitis B vaccine with large-HBs antigen

優れたB型肝炎予防ワクチン開発に成功 --既存ワクチンの弱点克服へ--. 京都大学プレスリリース. 2022-09-07.Although the current hepatitis B (HB) vaccine comprising small-HBs antigen (Ag) is potent and safe, attenuated prophylaxis against hepatitis B virus (HBV) with vaccine-escape mutations (VEMs) has been reported. We investigate an HB vaccine consisting of large-HBsAg that overcomes the shortcomings of the current HB vaccine. Yeast-derived large-HBsAg is immunized into rhesus macaques, and the neutralizing activities of the induced antibodies are compared with those of the current HB vaccine. Although the antibodies induced by the current HB vaccine cannot prevent HBV infection with VEMs, the large-HBsAg vaccine-induced antibodies neutralize those infections. The HBV genotypes that exhibited attenuated neutralization via these vaccines are different. Here, we show that the HB vaccine consisting of large-HBsAg is useful to compensate for the shortcomings of the current HB vaccine. The combined use of these HB vaccines may induce antibodies that can neutralize HBV strains with VEMs or multiple HBV genotypes

Adaptive radiotherapy based on the daily regression of a tumor in carbon-ion beam irradiation

We propose a new application of adaptive radiotherapy using a scanning beam, taking into account the daily regression of a tumor. No patient-specific hardware (such as collimators and compensating filters) is needed for the scanning technique; thus, it allows re-planning immediately before each fractional irradiation using the sophisticated conformations of dose distributions. We retrospectively modeled the tumor volume regression curves as a function of the dose from the CT images which were taken three times during the treatment course. The daily shape of the tumor was mathematically interpolated assuming constant continuity of the tumor deformation. We simulated the adaptive radiotherapy by optimizing the dose distribution on the estimated daily tumor volume for every fraction. The dose–volume histogram (DVH) for the organ at risk in the adaptive radiotherapy was compared with that of the current clinical protocol. We performed analysis using the CT images of cervical cancer patients who received carbon-ion radiotherapy in broad-beam irradiation. The DVH for the rectum and the sigmoid colon was improved by adaptive radiotherapy considering the inter-fractional tumor regression. The result shows that this approach has possible advantages

Carbon Ion Radiotherapy For Gynecological Melanoma

Objective : A clinical trial of carbon ion radiotherapy for gynecological melanoma was conducted under the Phase I/II clinical trial to assess the toxicity and efficacy.\nMethods : The eligibility criteria for enrollment in this study were (1) histologically proven malignant melanoma, (2) a localized measurable tumor in gynecological region, (3) at least a 5mm gap between the tumor and radiosensitive organs, including bowel and bladder, and (4) a expected prognosis of more than 6 months. In principle, tumors and surrounding areas were irradiated 3.6 GyE per fraction up to the total dose of 57.6 GyE in 16 fractions, 4 times a week. Toxicities were assessed weekly and graded according to NCI-CTCAE ver.4.0. Treatment response was assessed at 3 month after treatment completion. Statistical analysis of survival was calculated using the Kaplan-Meier method.\nResults : A series of 21 gynecological melanoma patients were treated with carbon ion radiotherapy between November 2004 and October 2011. The age ranged from 51 to 80 with a median of 71. The tumor sites were vagina in 13, vulva in 3, uterine cervix in 3 and vagina and vulva in 2. The clinical stage was stage I in 3, stage II in 9, stage III in 5, stage IVB in 1 and 3 patients had local recurrent tumor. The irradiated dose was 57.6 GyE in 20 and 64 GyE in 1. Twelve patients were treated with DAV-Feron regime (DTIC, ACNU, VCR, IFN-) and 4 patients treated with IFN- only for induction and /or adjuvant therapy. One patient had used IFN- during radiotherapy. Greater than 2 acute toxicities were observed with regard to grade 3 skin reaction in 2, grade 2 skin reaction in 4 and grade 2 urinary tract reaction in 1. The median follow-up times were 15 months (range 3-53 months) in all patients, 15 months (range 3-43 months) in the living and 16 months (range 11-53 months) in the dead. One patient who had been treated concurrent IFN- developed sepsis induced by urinary tract infection after 3 months from the completion of radiotherapy. Thirteen patients have recurred, in-field in 3, marginal field in 3, regional lymph node in 6 and distant in 6. All T1 tumors and all vulval tumors were locally controlled. Ten of 21 patients were dead, one was intercurrent disease and other 9 were of melanoma. The 2-year local control rate, disease free rate and overall survival rate were 71%, 38% and 53% respectively.\nConclusions : Carbon ion radiotherapy is as effective as surgery for gynecological melanoma.51st Annual Meeting of Particle Therapy Co-Operative Grou

Characteristics of sports-related emergency transport: A population-based descriptive study in Osaka city

Kosuke Kiyohara, Junya Sado, Tasuku Matsuyama, Yusuke Katayama, Sumito Hayashida, Ken Nakata, Tetsuhisa Kitamura, Characteristics of Sports-Related Emergency Transport: A Population-Based Descriptive Study in Osaka City, Journal of Epidemiology, 2020, Volume 30, Issue 6, Pages 268-275, Released June 05, 2020, [Advance publication] Released May 18, 2019, Online ISSN 1349-9092, Print ISSN 0917-5040, https://doi.org/10.2188/jea.JE20190019, https://www.jstage.jst.go.jp/article/jea/30/6/30_JE20190019/_article/-char/e

Dose-Volume Parameters in CT-based Image-guided Brachytherapy for Cervical Cancer

European Society for Therapeutic Radiology and Oncology　31（ESTRO31