Beneficial effects of Vitis coignetiae Pulliat leaves on nonalcoholic steatohepatitis in a rat model

Vitis coignetiae Pulliat (Yamabudo) is used as a health juice and wine based on the abundant polyphenols and anthocyanins in its fruit. However, it is not known whether the leaves of this plant confer similar benefits. This study investigated the hepatoprotective effects of aqueous extracts from Vitis coignetiae Pulliat leaves (VCPL) in an animal model of nonalcoholic steatohepatitis (NASH). Rats were fed a choline-deficient high-fat diet for four weeks to generate fatty livers. NASH was induced by oxidative stress loading. Ten weeks later, blood and liver samples were collected from anesthetized animals and assessed biochemically, histologically, and histochemically to determine the extent of oxidative stress injury and the overall effects of VCPL. Six-week VCPL extract supplementation reduced serum levels of liver enzymes, decreased CYP2E1 induction, increased plasma antioxidant activities and delayed the progression of liver fibrosis. The findings suggested that VCPL has strong radical-scavenging activity and may be beneficial in preventing NASH progression.</p

Water Extract of Vitis coignetiae Pulliat Leaves Attenuates Oxidative Stress and Inflammation in Progressive NASH Rats

This study aimed to investigate the therapeutic effects of the water extract of leaves of Vitis coignetiae Pulliat (VCPL) on nonalcoholic steatohepatitis (NASH) with advanced fibrosis, as our previous study exhibited its preventive effect on NASH. The NASH animal model [PCT/JP2007/52477] was prepared by loading recurrent and intermittent hypoxemia stress to a rat with fatty liver, which resembled the condition occurring in patients with obstructive sleep apnea (OSA) and fatty liver, who have a high incidence of NASH. Intermittent hypoxemia stress is regarded as a condition similar to warm ischemia followed by re-oxygenation, which induces oxidative stress (OS). The daily 100 or 300mg/kg VCPL administrations were performed for 3 weeks perorally beginning at the time of detection of advanced liver fibrosis. The therapeutic efficacy of VCPL on NASH was demonstrated by the reduction of the leakage of hepato-biliary enzymes and the amelioration of liver fibrosis. The OS elevation in NASH rats was measured based on the derivation of reactive oxygen species from liver mitochondrial energy metabolism and on the decrease in plasma SOD-like activity. The aggravation of inflammatory responses was demonstrated by the neutrophil infiltration (elevated myeloperoxidase activity) and the progression of fibrosis in the livers of NASH rats. In addition, the NASH rats without VCPL treatment also exhibited activation of nuclear factor-κB, a key factor in the link between oxidative stress and inflammation. All of these changes were reduced dose-dependently by the VCPL administration. These findings indicate that VCPL may improve hepatic fibrosis or at least suppress the progression of NASH, by breaking the crosstalk between OS and inflammation

Case Report Carbon Ion Beam Radiotherapy for Sinonasal Malignant Tumors Invading Skull Base

Objective. To evaluate the treatment outcome and prognostic factors in patients with sinonasal malignant tumors invading skull base. Study Design and Setting. A retrospective clinical study at the Yamagata University School of Medicine. Subjects and Methods. Three patients with sinonasal malignant tumors invading skull base were presented in present study. All patients were treated with carbon ion beam radiotherapy. The prescribed dose to the center of the clinical target volume was 64.0 GyE/16 fractions over 4 weeks at 4.0 GyE/fraction per day. Results. All patients completed carbon ion beam radiotherapy without an interval. The mean observation period was 39.6 months (range: 11-54 months). There were no local or regional recurrences in all cases; however, one patient had a metastasis in distant organs. Regarding the complications, visual loss was observed in one eye of one patient whose optic nerve was entirely involved by the tumor and field of carbon ion beam radiotherapy. Radiation induced brain injury was observed in two patients; however, these patients do not complain about neurological abnormality and had no treatment for radiation induced brain necrosis. Conclusions. Carbon ion beam radiotherapy for sinonasal malignant tumors invading the skull base showed therapeutic effectiveness

Brainstem NTCP and dose constraints for carbon ion RT—Application and translation from Japanese to European RBE-weighted dose

Background and Purpose: The Italian National Center of Oncological Hadrontherapy (CNAO) has applied dose constraints for carbon ion RT (CIRT) as defined by Japan’s National Institute of Radiological Sciences (NIRS). However, these institutions use different models to predict the relative biological effectiveness (RBE). CNAO applies the Local Effect Model I (LEM I), which in most clinical situations predicts higher RBE than NIRS’s Microdosimetric Kinetic Model (MKM). Equal constraints therefore become more restrictive at CNAO. Tolerance doses for the brainstem have not been validated for LEM I-weighted dose (DLEM I). However, brainstem constraints and a Normal Tissue Complication Probability (NTCP) model were recently reported for MKM-weighted dose (DMKM), showing that a constraint relaxation to DMKM|0.7 cm3 <30 Gy (RBE) and DMKM|0.1 cm3 <40 Gy (RBE) was feasible. The aim of this work was to evaluate the brainstem NTCP associated with CNAO’s current clinical practice and to propose new brainstem constraints for LEM I-optimized CIRT at CNAO. Material and Methods: We reproduced the absorbed dose of 30 representative patient treatment plans from CNAO. Subsequently, we calculated both DLEM I and DMKM, and the relationship between DMKM and DLEM I for various brainstem dose metrics was analyzed. Furthermore, the NTCP model developed for DMKM was applied to estimate the NTCPs of the delivered plans. Results: The translation of CNAO treatment plans to DMKM confirmed that the former CNAO constraints were conservative compared with DMKM constraints. Estimated NTCPs were 0% for all but one case, in which the NTCP was 2%. The relationship DMKM/DLEM I could be described by a quadratic regression model which revealed that the validated DMKM constraints corresponded to DLEM I|0.7 cm3 <41 Gy (RBE) (95% CI, 38–44 Gy (RBE)) and DLEM I|0.1 cm3 <49 Gy (RBE) (95% CI, 46–52 Gy (RBE)). Conclusion: Our study demonstrates that RBE-weighted dose translation is of crucial importance in order to exchange experience and thus harmonize CIRT treatments globally. To mitigate uncertainties involved, we propose to use the lower bound of the 95% CI of the translation estimates, i.e., DLEM I|0.7 cm3 <38 Gy (RBE) and DLEM I|0.1 cm3 <46 Gy (RBE) as brainstem dose constraints for 16 fraction CIRT treatments optimized with LEM I.publishedVersio

Carbon ion radiotherapy for basal cell adenocarcinoma of the head and neck: preliminary report of six cases and review of the literature

<p>Abstract</p> <p>Background</p> <p>Basal cell adenocarcinoma accounts for approximately 1.6% of all salivary gland neoplasms. In this report, we describe our experiences of treatment for BCAC with carbon ion radiotherapy in our institution.</p> <p>Methods</p> <p>Case records of 6 patients with diagnosis of basal cell adenocarcinoma of the head and neck, who were treated by carbon ion radiotherapy with 64.0 GyE/16 fractions in our institution, were retrospectively reviewed.</p> <p>Results</p> <p>In a mean follow-up period of 32.1 months (14.0-51.3 months), overall survival and local control rates of 100% were achieved. Only one grade 4 (CTCAE v3.0) late complication occurred. There was no other grade 3 or higher toxicity.</p> <p>Conclusions</p> <p>Carbon ion radiotherapy should be considered as an appropriate curative approach for treatment of basal cell adenocarcinoma in certain cases, particularly in cases of unresectable disease and postoperative gross residual or recurrent disease.</p

Comparison of percutaneous radiofrequency thermal ablation and surgical resection for small hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>The purpose of this investigation was to compare the outcome of percutaneous radiofrequency thermal ablation therapy (PRFA) with surgical resection (SR) in the treatment of single and small hepatocellular carcinoma (HCC).</p> <p>Methods</p> <p>We conducted a retrospective cohort study on 231 treatment naive patients with a single HCC ≤ 3 cm who had received either curative PRFA (162 patients) or curative SR (69 patients). All patients were regularly followed up after treatment at our department with blood and radiologic tests.</p> <p>Results</p> <p>The 1-, 3- and 5-year overall survival rates after PRFA and SR were 95.4%, 79.6% and 63.1%, respectively in the PRFA group and 100%, 81.4% and 74.6%, respectively in the SR group. The corresponding recurrence free survival rates at 1, 3 and 5 years after PRFA and SR were 82.0%, 38.3% and 18.0%, respectively in the PRFA group and 86.0%, 47.2% and 26.0%, respectively in the SR group. In terms of overall survival and recurrence free survival, there were no significant differences between these two groups. In comparison of PRFA group patients with liver cirrhosis (LC) (n = 127) and SR group patients with LC (n = 50) and in comparison of PRFA group patients without LC (n = 35) and SR group patients without LC (n = 19), there were also no significant differences between two groups in terms of overall survival and recurrence free survival. In the multivariate analysis of the risk factors contributing to overall survival, serum albumin level was the sole significant factor. In the multivariate analysis of the risk factors contributing to recurrence free survival, presence of LC was the sole significant factor. The rate of serious adverse events in the SR group was significantly higher than that in the PRFA group (P = 0.023). Hospitalization length in the SR group was significantly longer than in the PRFA group (P = 0.013).</p> <p>Conclusions</p> <p>PRFA is as effective as SR in the treatment of single and small HCC, and is less invasive than SR. Therefore, PRFA could be a first choice for the treatment of single and small HCC.</p

Non-human primate model of amyotrophic lateral sclerosis with cytoplasmic mislocalization of TDP-43

Amyotrophic lateral sclerosis is a fatal neurodegenerative disease characterized by progressive motoneuron loss. Redistribution of transactive response deoxyribonucleic acid-binding protein 43 from the nucleus to the cytoplasm and the presence of cystatin C-positive Bunina bodies are considered pathological hallmarks of amyotrophic lateral sclerosis, but their significance has not been fully elucidated. Since all reported rodent transgenic models using wild-type transactive response deoxyribonucleic acid-binding protein 43 failed to recapitulate these features, we expected a species difference and aimed to make a non-human primate model of amyotrophic lateral sclerosis. We overexpressed wild-type human transactive response deoxyribonucleic acid-binding protein 43 in spinal cords of cynomolgus monkeys and rats by injecting adeno-associated virus vector into the cervical cord, and examined the phenotype using behavioural, electrophysiological, neuropathological and biochemical analyses. These monkeys developed progressive motor weakness and muscle atrophy with fasciculation in distal hand muscles first. They also showed regional cytoplasmic transactive response deoxyribonucleic acid-binding protein 43 mislocalization with loss of nuclear transactive response deoxyribonucleic acid-binding protein 43 staining in the lateral nuclear group of spinal cord innervating distal hand muscles and cystatin C-positive cytoplasmic aggregates, reminiscent of the spinal cord pathology of patients with amyotrophic lateral sclerosis. Transactive response deoxyribonucleic acid-binding protein 43 mislocalization was an early or presymptomatic event and was later associated with neuron loss. These findings suggest that the transactive response deoxyribonucleic acid-binding protein 43 mislocalization leads to α-motoneuron degeneration. Furthermore, truncation of transactive response deoxyribonucleic acid-binding protein 43 was not a prerequisite for motoneuronal degeneration, and phosphorylation of transactive response deoxyribonucleic acid-binding protein 43 occurred after degeneration had begun. In contrast, similarly prepared rat models expressed transactive response deoxyribonucleic acid-binding protein 43 only in the nucleus of motoneurons. There is thus a species difference in transactive response deoxyribonucleic acid-binding protein 43 pathology, and our monkey model recapitulates amyotrophic lateral sclerosis pathology to a greater extent than rodent models, providing a valuable tool for studying the pathogenesis of sporadic amyotrophic lateral sclerosis

Outcom of visual acuity in carbon ion radiotherapy-Analysis of the DVHs and prognostic factor-

PURPOSE: To analyze the prognostic factor in late morbidity of visual acuity in carbon ion radiotherapy for head and neck cancer. METHODS AND MATERIALS: Between June 1994 to March 2000, 163 patients with head and neck tumor were treated with carbon ions. Selected for this study were 30 patients (54 optic nerves (ONs) ), whose ONs with the primary tumor were included in high dose area, who had no evidence of visual impairment before radiotherapy, and who had follow up period more than 2 years. The median age of 30 patients was 57.2 years with 14 males and 16 females. Median prescribed total dose was 56.0 gray equivalent (GyE) (range, 48-64 GyE). Age, gender, KI, anemia, blood pressure and dose of ONs were listed as prognostic factors. The dose of ONs was delivered from DVHs calculated from planning CT. All patients were informed the possibility of visual impairment before treatment. RESULTS: Eleven ONs showed decrease of visual acuity at an average of 19.6-month and eventually progressed to visual loss at 25.6-month after irradiation. All of them, the ONs were involved within tumor. Thereby, it was unavoidable to exclude a part of or all ON from the PTV. Median maximum dose of the ON was 49.6GyE. Thirty-four ONs irradiated by less than 56 GyE (maximum-dose) resulted in no visual impairment. On the other hand, in 20 ONs irradiated by more than 56 GyE, a decrease of visual acuity was observed in 11 ONs (55%). Multivariate analysis revealed anemia and D0.30 as unfavorable prognostic factors.CONCLUSION: None of the unexpected morbidity had been observed in this treatment. The dose-complication probability of visual acuity in carbon ion radiotherapy was confirmed in this study. The data suggested that D0.30 was a good predictor for the tolerance dose.International Stereotactic Radiosurgery Society Congres