Particle therapy using carbon ions or protons as a definitive therapy for patients with primary sacral chordoma.

OBJECTIVE: This study retrospectively evaluated the efficacy and toxicity of particle therapy using carbon ions or protons for primary sacral chordomas. METHODS: We evaluated 23 patients with primary sacral chordoma treated with carbon ion therapy (CIT) or proton therapy (PT) between July 2005 and June 2011 at the Hyogo Ion Beam Medical Center, Hyogo, Japan. The median patient age was 72 years. 14 patients were treated with 70.4 Gy equivalents (GyE) in 16 fractions and 9 were treated with 70.4 GyE in 32 fractions. CIT was used for 16 patients, and PT was used for 7 patients. RESULTS: The median follow-up period was 38 months. At 3 years, local control (LC), overall survival (OS) and progression-free survival (PFS) for all patients were 94%, 83% and 68%, respectively. The log-rank test revealed that male sex was significantly related to better PFS (p=0.029). No other factors, including dose fractionation and ion type, were significant for LC, OS or PFS. In nine patients, ≥ Grade 3 acute dermatitis was observed, and ≥ Grade 3 late toxicities were observed in nine patients. The 32-fraction protocol reduced severe toxicities in both the acute and late phases compared with the 16-fraction protocol. CONCLUSION: Particle therapy for patients with sacral chordoma showed favourable LC and OS. Severe toxicities were successfully reduced by modifying the dose fractionation and treatment planning in the later treatment era. Thus, this therapeutic modality should be considered useful and safe. ADVANCES IN KNOWLEDGE: This is the first study including both CIT and PT for sacral chordomas.

Particle therapy for mucosal melanoma of the head and neck. A single-institution retrospective comparison of proton and carbon ion therapy.

PURPOSE: To retrospectively analyze treatment outcomes after particle therapy using protons or carbon ions for mucosal melanoma of the head and neck (HNMM) at the Hyogo Ion Beam Medical Center, as well as to compare proton therapy (PT) and carbon ion therapy (CIT). PATIENTS AND METHODS: Data from 62 HNMM patients without metastasis, treated with PT or CIT between October 2003 and April 2011 were analyzed. Median patient age was 70.5 years (range 33-89 years). Of the total patients, 33 (53 %) had received PT and 29 (47 %) had undergone CIT. Protocols for 65 or 70.2 GyE in 26 fractions were used for both ion types. RESULTS: Median follow-up was 18.0 months (range 5.2-82.7 months). The 1-/2-year overall survival (OS) and local control (LC) rates were 93 %/61 % and 93 %/78 % for all patients, 91 %/44 % and 92 %/71 % for the PT patients and 96 %/62 % and 95 %/59 % for the CIT patients, respectively. No significant differences were observed between PT and CIT. Local recurrence was observed in 8 patients (PT: 5, CIT: 3) and 29 (PT: 18, CIT: 11) experienced distant metastases. Acute reactions were acceptable and all patients completed the planned radiotherapy. Regarding late toxicity, grade 3 or greater events were observed in 5 patients (PT: 3, CIT: 2), but no significant difference was observed between PT and CIT. CONCLUSION: Our single-institution retrospective analysis demonstrated that particle therapy for HNMM achieved good LC, but OS was unsatisfactory. There were no significant differences between PT and CIT in terms of either efficacy or toxicity.

Herbal medicines, Sairei-to and Tokishakuyaku-san, differently modulate the release of cytokines from decidual versus peripheral blood mononuclear cells.

PROBLEM AND METHOD OF STUDY: We have shown that Tokishakuyaku-san (Toki) and Sairei-to (Sai) enhance T helper-1 (Th1) cytokine release from peripheral blood mononuclear cells (PBMCs): thereby, they could be a therapeutic means in the treatment of autoimmunity related recurrent abortion in which T helper-2 (Th2) polarization is exaggerated, the condition purported to benefit from these herbal medicines. However, an open question is whether these medicines might enhance Th1 cytokine release in decidual tissues and thereby stimulate the killer activity, thus, working counterproductively by accelerating maternal alloimmune reactions toward fetal tissues. To address this, we examined the effects of these medicines on the release of cytokines from decidual mononuclear cells (DMCs) in comparison with PBMCs on the assumption that they might act differently on these cell types. The effects of these medicines were investigated as related to human leukocyte antigen (HLA)-G, a nonclassical HLA class I antigen expressed on trophoblasts and a putative crucial player involved in fetomaternal immune interplay. RESULTS: Regarding Th1 cytokines. Toki marginally increased the release of tumor necrosis factor (TNF)-alpha, but not interferon (IFN)-gamma from DMCs while Sai did not affect the release of both. Both Toki and Sai were without effect in modulating the release of interleukin (IL)-4, a member of Th2 cytokines. Interestingly, the presence of HLA-G reduced the release of Th1 cytokines from DMCs regardless of the addition of Toki, Sai or none. These findings are in sharp contrast with PBMCs on which these medicines seem to act so as to enhance Th1 polarization and attenuate Th2 polarization. CONCLUSION: Differential effects of Toki and Sai on the release of Th1/Th2 cytokines between DMCs and PBMCs may afford the rationale of these medicines in the treatment of autoimmunity-related recurrent abortion.

Occurrence of toxicity and cell proliferation after a single gavage administration of chloroform to male F344 rats.

Chloroform, an industrial solvent and one of the most common environmental contaminants which produces carcinogenic effects in the liver and kidney of rodents, is not genotoxic in most traditional bacterial and mammalian test systems. Its carcinogenic potential appears attributable to the sustained cell turnover (regenerative hyperplasia) which results from chronic chloroform toxicity. In this present study, cell proliferation (replicative DNA synthesis, RDS) and histopathological changes in hepatocytes and renal tubular epithelial cells were assessed in male F344 rats following a single gavage chloroform exposure (50, 150 or 500 mg/kg). In addition, biochemical parameters (BUN, GOT, LDH and NAG) were examined using plasma and urine samples. Cell proliferation and histopathological changes (e.g. hypertrophy, necrosis, vacuolation) were only seen at the dose of 500 mg/kg in the liver and kidney. At the same dose, all biochemical markers were increased at the 24 to 48 hr time points. These results obtained are thus in line with earlier findings pointing to epigenetic carcinogenicity.

Photooxidation of hypotaurine to taurine in the presence of flavins.

Irradiation of organic sulfinates such as hypotaurine and cysteine sulfinic acid in the presence of catalytic amounts of flavins led to the oxidation of its sulfinic groups (-SO2H) to the corresponding sulfonates. The process of hypotaurine oxidation in the presence of riboflavin, followed by absorbance decrease at 220 nm and by ion-exchange chromatography, showed a pseudo-first-order kinetics at pH 6.0. The k value depended linearly on flavin concentrations. The reaction rate was higher at acidic pH. Although the reaction rate was not affected by the addition of superoxide dismutase or catalase, superoxide ions were supposed to be by-products of the reaction. The effectiveness of allyl alcohol as a scavenger pointed to a free-radical mechanism of the reaction. We propose a new reaction mechanism involving sulfinic radicals on this photochemical reaction.

Immaturity of the enzyme activity and the response to inducers of rat liver cysteine dioxygenase during development.

Cysteine dioxygenase activity was not detected in the liver of either fetal or 2-day-old rat. The enzyme activity of neonatal rat liver gradually increased between the 4th and 12th postnatal days and then sharply increased to reach the adult level by the 28th postnatal day. No cysteine dioxygenase activity was observed in the fetal liver at the 18th day of gestation from a dam injected with hydrocortisone. Hydrocortisone-mediated induction was first observed in the livers of 4-day-old rats. The duration of hydrocortisone-mediated induction was much longer in the livers of 4- to 12-day-old rats than in those of adult rats. The enzyme half-life in livers of 10- and 20-day-old rats was 6.4 and 3.7 h, respectively. The half-life of the enzyme in 20-day-old rat liver was increased to 6.2 h by L-cysteine injection.