Conformational studies of mitochondrial DNA

Ring DNA from rat liver mitochondria has been examined by circular dichroism (CD) in the region of the 225 to 320 m/~ and the followings have been clarified. The ring DNA gives a CD spectral curve somewhat different from linear DNA from nuclei, showing a big positive peak at 266 m/~ and a small negative band at 243 m!~. That is, the positive CD band of ring DNA shifted by about 7 m/~ to the shorter wavelength side from the band of the ordinary nuclear DNA, 273 m!~. Negative band appeared at the same region as that of linear DNA but reduced in depth. Heat denaturation of the ring DNA induced a red shift of the positive band, by about 4 mp., but no change in negative band. From these experimental results it has been concluded that the ring DNA has highly twisted conformation and high in G.C contents, both of which are responsible for the blue shift of the CD spectrum.</p

Newton's law in de Sitter brane

Newton potential has been evaluated for the case of dS brane embedded in Minkowski, dS$_5$ and AdS$_5$ bulks. We point out that only the AdS$_5$ bulk might be consistent with the Newton's law from the brane-world viewpoint when we respect a small cosmological constant observed at present universe.Comment: 9 pages, 1 figure, LaTe

Scalar field localization on a brane with cosmological constant

We address the localization of a scalar field, whose bulk-mass M is considered in a wide range including the tachyonic region,on a three-brane. The brane with non-zero cosmological constant $\lambda$ is embedded in five dimensional bulk space. We find in this case that the trapped scalar could have mass $m$ which has an upper bound and expressed as $m^2=m_0^2+\alpha M^2\leq \beta |\lambda|$ with the calculable numbers $m_0^2, \alpha, \beta$. We point out that this result would be important to study the stability of the brane and cosmological problems based on the brane-world.Comment: 14 pages, 5 figure

Context-dependent activation of Wnt signaling by tumor suppressor RUNX3 in gastric cancer cells

RUNX3 is a tumor suppressor for a variety of cancers. RUNX3 suppresses the canonical Wnt signaling pathway by binding to the TCF4/β-catenin complex, resulting in the inhibition of binding of the complex to the Wnt target gene promoter. Here, we confirmed that RUNX3 suppressed Wnt signaling activity in several gastric cancer cell lines; however, we found that RUNX3 increased the Wnt signaling activity in KatoIII and SNU668 gastric cancer cells. Notably, RUNX3 expression increased the ratio of the Wnt signaling-high population in the KatoIII cells. although the maximum Wnt activation level of individual cells was similar to that in the control. As found previously, RUNX3 also binds to TCF4 and β-catenin in KatoIII cells, suggesting that these molecules form a ternary complex. Moreover, the ChIP analyses revealed that TCF4, β-catenin and RUNX3 bind the promoter region of the Wnt target genes, Axin2 and c-Myc, and the occupancy of TCF4 and β-catenin in these promoter regions is increased by the RUNX3 expression. These results suggest that RUNX3 stabilizes the TCF4/β-catenin complex on the Wnt target gene promoter in KatoIII cells, leading to activation of Wnt signaling. Although RUNX3 increased the Wnt signaling activity, its expression resulted in suppression of tumorigenesis of KatoIII cells, indicating that RUNX3 plays a tumor-suppressing role in KatoIII cells through a Wnt-independent mechanism. These results indicate that RUNX3 can either suppress or activate the Wnt signaling pathway through its binding to the TCF4/β-catenin complex by cell context-dependent mechanisms. © 2014 The Authors

Efficacy of mizoribine pulse therapy in patients with rheumatoid arthritis who show a reduced or insufficient response to infliximab

The efficacy of infliximab, a chimeric antibody against tumor necrosis factor-α used to treat patients with rheumatoid arthritis (RA), tends to decrease as patients develop human antichimeric antibody against infliximab (HACA). The clinical study reported here was designed to evaluate the efficacy of mizoribine (MZR) pulse therapy in patients who show a reduced or insufficient response to infliximab. Ten RA patients who had active arthritis despite infliximab therapy were treated with MZR pulse therapy at a dose of 100 mg MZR and methotrexate (MTX) and the disease activity assessed at baseline and at weeks 4–8, 12–16, and 20–24. The dose was increased to 150 mg in those patients who showed an insufficient response to MZR. The mean 28-joint disease activity score (DAS28) at weeks 12–16 and 20–24 of therapy was significantly lower than that at baseline. A moderate or good European League against Rheumatism (EULAR) response was achieved in seven patients (70%) at weeks 12–16 and in five patients (50%) at weeks 20–24. The dose of 150 mg MZR was effective in one of the three patients who showed an insufficient response to pulse therapy with 100 mg MZR. Based on these results, we propose that MZR pulse therapy should be attempted before the patient is switched to other biologics

Effectiveness of Anti-PD-1 Antibody Monotherapy for the Primary Malignant Melanoma of the Esophagus： A Case Report

Primary malignant melanoma of the esophagus（PMME）is extraordinarily rare with a high degree of malignancy and poor prognosis, and a standard therapy remains to be established. The anti-PD-1 antibody nivolumab is a promising agent for various cancers. To our knowledge, this is the first case report of PMME where a complete response was achieved using nivolumab. We report an 80-year-old woman who was diagnosed with PMME with bone metastasis and lymph node metastases. Although dacarbazine combined chemotherapy was performed and continued for six cycles, the primary tumor progressed and liver metastases appeared. The patient then received nivolumab monotherapy. After three cycles, nivolumab monotherapy for PMME resulted in a complete response as shown by positron emission tomography, computed tomography, and esophagogastroduodenoscopy. In our case, nivolumab exerted a curative effect on PMME, thus suggesting that nivolumab can be effective in the treatment of this rare disease