アクセイ シンケイ コウシュ ニ タイスル チュウセイシ ホソク リョウホウ : コンゴウ ビーム ネツチュウセイシ ト ネツガイチュウセイシ ビーム オ モチイタ アタラシイ チリョウ センリャク

The purpose of this study was to clarify the clinical interim results of boron neutron capture therapy (BNCT) using mixed epithermal-and thermal neutron beams in patients with malignant glioma. The mixed neutron beam for BNCT has been used clinically since 1998. Its great advantage consists of its greater ability than the pure thermal neutron beam to reach sites deep from the brain surface. Sixteen patients with malignant glioma (glioblastoma n=14, anaplastic ependymoma n=1, PNET n=1) underwent mixed epithermal-and thermal neutron beam treatment between 1998 and 2003. They included 2 children younger than 3 years. Sodium borocaptate (Na2B12H11SH, BSH ; 80-100 mg/kg) was administered intravenously at 12-15 hr before neutron irradiation. The radiation dose (i.e. physical dose of boron n-alpha reaction) in the he protocol used between 1997 and 2000 (Protocol A) prescribed a maximum tumor volume dose of 15 Gy. In 2001, a new dose-escalated protocol was introduced (Protocol B) ; it prescribes a minimum tumor volume dose of 18 Gy or, alternatively, a minimum target volume dose of 15 Gy. In both protocols, the maximum vascular radiation dose to the brain surface is not to exceed 15 Gy. Of the 12 patients, 8 were treated according to Protocols A and 4 according to Protocol B. Since 2002, the radiation dose was reduced to 80-90% dose of Protocol B because of acute radiation injury. A new Protocol was applied to four glioblastoma patients (Protocol C). Of the 8 patients treated under Protocol A, 7 died (dissemination n=4, local recurrence, infection, unknown causes, n=1 each). Of the 4 patients treated under Protocol B, 2 died. Concerning the adverse effects of BNCT, Protocol B resulted in higher complication rates with respect to both acute and delayed radiation injury. The estimated median survival time after diagnosis and after BNCT in all patients were 16.7 and 14.6 months, respectively. In 8 patients of Protocol A, the estimated median survival time after diagnosis was 16.0 months ; 1-year and 2-year survival rate were 75.0% and 12.5%, respectively. On the other hand, in 8 patients in Protocol B and C, the estimated median survival time after diagnosis was 15.5 months ; 1-year and 2-year survival rate were 80.0% and 53.3%, respectively. Our limited clinical evaluation suggests that BNCT could achieve local control of glioblastomas at the primary site and that possible dose escalation is limited. While the dose escalation can contribute to the improvement of survival rate, it results in the radiation injury. We conclude that not only the radiation dose at the target point, but also the distribution of neutron flux in the radiation field may contribute to the cure of glioblastoma by BNCT. Computation-assisted dose planning can contribute to improved clinical results following BNCT and to the prevention of cerebrospinal fluid dissemination. We will introduce pure epithermal neutron beam instead of mixed neutron beam in the near future. It has greater advantage than mixed neutron beam to deep-seated glioma because it has a peak in neutron flux at 2-3 cm depth from the brain surface. The dose-planning system and pure epithermal neutron beam can lead to further improvements in the clinical outcomes and the avoidance of adverse effects in brain tumor patients subjected to BNCT

Observations and Modeling of Rainfall and Sediment Runoff in the Lesti River Basin, Tributary of the Brantas River, Indonesia

Source: ICHE Conference Archive - https://mdi-de.baw.de/icheArchiv

Boron neutron capture therapy (BNCT) for newly-diagnosed glioblastoma : Comparison of clinical results obtained with BNCT and conventional treatment

The purpose of this study was to evaluate the clinical outcome of boron neutron capture therapy (BNCT) and conventional treatment in patients with newly diagnosed glioblastoma. Since 1998 we treated 23 newly-diagosed GBM patients with BNCT without any additional chemotherapy. Their median survival time was 19.5 months ; the 2-, 3-, and 5-year survival rates were 31.8%, 22.7%, and 9.1%, respectively. The clinical results of BNCT in patients with GBM are similar to those of recent conventional treatments based on radiotherapy with concomitant and adjuvant temozolomide

Regulation of energy metabolism by interleukin-1 β, but not by interleukin-6, is mediated by nitric oxide in primary cultured rat hepatocytes

AbstractThe effects of inflammatory cytokines (interleukin-1 β, interleukin-6, and tumor necrosis factor-α) on energy metabolism were studied in primary cultured rat hepatocytes. Adenine nucleotide (ATP, ADP, and AMP) content, lactate production, the ketone body ratio (acetoacetate/β-hydroxybutyrate) reflecting the liver mitochondrial redox state (NAD+/NADH), and nitric oxide formation were measured. Insulin increased ATP content in hepatocytes and had a maximal effect after 8–12 h of culture. Both interleukin-1β and interleukin-6, but not tumor necrosis factor-α, significantly inhibited the ATP increase time- and dose-dependently. Interleukin-1β and interleukin-6 also stimulated lactate production. During the same period, interleukin-1 β but not interleukin-6 decreased the ketone body ratio. Furthermore, interleukin-1 β markedly stimulated nitric oxide formation in hepatocytes, and this increase was blocked by NG-monomethyl-L-arginine (a nitric oxide synthase inhibitor) and by interleukin-1 receptor antagonist. NG-monomethyl-l-arginine reversed inhibition of the ATP increase, decrease in the ketone body ratio, and increase in lactate production, which were induced by interleukin-lβ. Interleukin-1 receptor antagonist completely abolished all of the effects induced by interleukin-1 β. These results demonstrated that interleukin-1 β and interleukin-6 affect the insulin-induced energy metabolism in rat hepatocytes by different mechanisms. Specifically, interleukin-1 β inhibits ATP synthesis by causing the mitochondrial dysfunction, a process which may be mediated by nitric oxide

Antidepressant Response and Stress Resilience Are Promoted by CART Peptides in GABAergic Neurons of the Anterior Cingulate Cortex

[Background] A key challenge in the understanding and treatment of depression is identifying cell types and molecular mechanisms that mediate behavioral responses to antidepressant drugs. Because treatment responses in clinical depression are heterogeneous, it is crucial to examine treatment responders and nonresponders in preclinical studies. [Methods] We used the large variance in behavioral responses to long-term treatment with multiple classes of antidepressant drugs in different inbred mouse strains and classified the mice into responders and nonresponders based on their response in the forced swim test. Medial prefrontal cortex tissues were subjected to RNA sequencing to identify molecules that are consistently associated across antidepressant responders. We developed and used virus-mediated gene transfer to induce the gene of interest in specific cell types and performed forced swim, sucrose preference, social interaction, and open field tests to investigate antidepressant-like and anxiety-like behaviors. [Results] Cartpt expression was consistently upregulated in responders to four types of antidepressants but not in nonresponders in different mice strains. Responder mice given a single dose of ketamine, a fast-acting non–monoamine-based antidepressant, exhibited high CART peptide expression. CART peptide overexpression in the GABAergic (gamma-aminobutyric acidergic) neurons of the anterior cingulate cortex led to antidepressant-like behavior and drove chronic stress resiliency independently of mouse genetic background. [Conclusions] These data demonstrate that activation of CART peptide signaling in GABAergic neurons of the anterior cingulate cortex is a common molecular mechanism across antidepressant responders and that this pathway also drives stress resilience

上皮成長因子受容体を標的とした結腸直腸腫瘍の分子イメージング : 動物モデルにおける腫瘍の検出と治療評価

To overcome the problem of overlooking colorectal tumors, a new and highly sensitive modality of colonoscopy is needed. Moreover, it is also important to establish a new modality to evaluate viable tumor volume in primary lesions of colorectal cancer (CRC) during chemotherapy. Therefore, we carried out molecular imaging of colorectal tumors targeting epidermal growth factor receptor (EGFR), which is highly expressed on tumor cells, for evaluating chemotherapeutic efficacy and for endoscopic detection of colorectal adenomas. We first attempted to image five CRC cell lines with various levels of EGFR expression using an Alexa Fluor‐labeled anti‐EGFR monoclonal antibody (AF‐EGFR‐Ab). A strong fluorescence signal was observed in the cells depending on the level of EGFR expression. When nude mice xenografted with LIM1215 CRC cells, which highly express EGFR, were i.v. injected with AF‐EGFR‐Ab, a strong fluorescence signal appeared in the tumor with a high signal to noise ratio, peaking at 48 hours after injection and then gradually decreasing, as shown using an IVIS Spectrum system. When the xenografted mice were treated with 5‐fluorouracil, fluorescence intensity in the tumor decreased in proportion to the viable tumor cell volume. Moreover, when the colorectum of azoxymethane‐treated rats was observed using a thin fluorescent endoscope with AF‐EGFR‐Ab, all 10 small colorectal adenomas (≤3 mm) were detected with a clear fluorescence signal. These preliminary results of animal experiments suggest that EGFR‐targeted fluorescent molecular imaging may be useful for quantitatively evaluating cell viability in CRC during chemotherapy, and also for detecting small adenomas using a fluorescent endoscope

Current status of hematopoietic stem cell transplantation and umbilical cord blood bank in Chugoku-Shikoku area

The hematopoietic stem cell transplantation (HSCT) is rapidly and widely spreading in the treatment strategy of various types of cancers, since peripheral and umbilical cord blood (CB) have been introduced as new sources of transplantable cells in addition to ordinary bone marrow cells. In this report, the current status of HSCT was reviewed. CB is rich in hematopoietic stem/progenitor cells, which have high proliferative potential. T cells in CB are speculated to be immature and immune-tolerable cells with less potential to cause acute or chronic graft versus host disease (GVHD), which are directly related with transplant-related morbidity and mortality. Furthermore, transplants with CB are not strictly restricted by a HLA-disparity. On the other hand, the less number of collected cells from CB is a major problem when the cells are applied for clinical transplantation, because the lower number of infused cells often result in engraftment failure. Further, we have no data of the viability after long term cryopreservation. We must carefully judge the usefulness of CB as a cell source for transplantation, but the benefits of CB may have a possibility to overcome these disadvantage in the near future. Finally, the activity of cord blood bank in Chugoku-Shikoku area, which was started from August 1998, was also introduced

Relationship between advanced glycation end products and plaque progression in patients with acute coronary syndrome: the JAPAN-ACS Sub-study.

Background: The Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome (JAPAN-ACS) trial demonstrated that early aggressive statin therapy in patients with ACS significantly reduces plaque volume (PV). Advanced glycation end products (AGEs) and the receptors of AGEs (RAGE) may lead to angiopathy in diabetes mellitus (DM) and may affect on the development of coronary PV. The present sub-study of JAPAN-ACS investigates the association between AGEs and RAGE, and PV.Methods: Intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) was undertaken, followed by the initiation of statin treatment (either 4 mg/day of pitavastatin or 20 mg/day of atorvastatin), in patients with ACS. In the 208 JAPAN-ACS subjects, PV using IVUS in non-culprit segment > 5 mm proximal or distal to the culprit lesion and, serum levels of AGEs and soluble RAGE (sRAGE) were measured at baseline and 8-12 months after PCI.Results: At baseline, no differences in the levels of either AGEs or sRAGE were found between patients with DM and those without DM. The levels of AGEs decreased significantly with statin therapy from 8.6 ± 2.2 to 8.0 ± 2.1 U/ml (p < 0.001), whereas the levels of sRAGE did not change. There were no significant correlations between changes in PV and the changes in levels of AGEs as well as sRAGE. However, high baseline AGEs levels were significantly associated with plaque progression (odds ratio, 1.21; 95% confidence interval, 1.01 - 1.48; p = 0.044) even after adjusting for DM in multivariate logistic regression models.Conclusions: High baseline AGEs levels were associated with plaque progression in the JAPAN-ACS trial. This relationship was independent of DM. These findings suggest AGEs may be related to long-term glucose control and other oxidative stresses in ACS.Trial registration: NCT00242944. © 2013 Fukushima et al.; licensee BioMed Central Ltd

Mathematical Proof of Genomic Amino Acid Composition Homogeneity Based on Putative Small Units

The amino acid composition calculated from a gene assembly coding more than 3,000-7,000 amino acid residues represents the species specific amino acid composition based on the complete genome. In the present mathematical study, the 17 amino acid composition based on the sample size, 3,000-7,000, represents an amino acid composition with 95% level simultaneous confidence intervals for all amino acid probabilities in the sample. A genomic structure is constructed homogeneously with putative small units coding similar amino acid compositions under a mathematical rule