Irinotecan Plus Mitomycin C as Second-Line Chemotherapy for Advanced Gastric Cancer Resistant to Fluoropyrimidine and Cisplatin: A Retrospective Study

Background. S-1 plus cisplatin has been established to be standard first-line chemotherapy for advanced gastric cancer in Japan. The optimal second-line treatment refractory to S-1 plus cisplatin remains unclear. Methods. We retrospectively studied the efficacy, toxicity, and survival of irinotecan plus mitomycin C in patients with advanced gastric cancer refractory to a fluoropyrimidine plus cisplatin. Results. Twenty-four patients were studied. Prior chemotherapy was S-1 plus cisplatin in 15 patients, S-1 plus cisplatin and docetaxel in 8, and 5-fluorouracil plus cisplatin with radiotherapy in 1. The overall response rate was 17.4%. The median overall survival was 8.6 months, and the median progression-free survival was 3.6 months. Grade 3 or 4 toxicities included leukopenia (33%), neutropenia (50%), anemia (33%), thrombocytopenia (4%), anorexia (13%), diarrhea (4%), and febrile neutropenia (13%). Conclusion. A combination of irinotecan and mitomycin C is potentially effective in patients with advanced gastric cancer refractory to a fluoropyrimidine plus cisplatin

Single-nucleotide polymorphisms in HORMAD1 may be a risk factor for azoospermia caused by meiotic arrest in Japanese patients

金沢大学医薬保健研究域医学系Genetic mechanisms are implicated as a cause of some male infertility, yet are poorly understood. Meiosis is unique to germ cells and essential for reproduction. The synaptonemal complex is a critical component for chromosome pairing, segregation and recombination. Hormad1 is essential for mammalian gametogenesis as knockout male mice are infertile. Hormad1-deficient testes exhibit meiotic arrest in the early pachytene stage and synaptonemal complexes cannot be visualized. To analyze the hypothesis that the human HORMAD1 gene defects are associated with human azoospermia caused by meiotic arrest, mutational analysis was performed in all coding regions by direct sequence analysis of 30 Japanese men diagnosed with azoospermia resulting from meiotic arrest. By the sequence analysis, three polymorphism sites, Single Nucleotide Polymorphism 1 (c. 163A>G), SNP2 (c. 501T>G) and SNP3 (c. 918C>T), were found in exons 3, 8 and 10. The 30 patients with azoospermia and 80 normal pregnancy-proven, fertile men were analyzed for HORMAD1 polymorphisms. Both SNP1 and SNP2 were associated with human azoospermia caused by complete early meiotic arrest (P<0.05). We suggest that the HORMAD1 has an essential meiotic function in human spermatogenesis. © 2012 AJA, SIMM & SJTU. All rights reserved

Delta degrees of freedom in antisymmetrized molecular dynamics and (p,p') reactions in the delta region

Delta degrees of freedom are introduced into antisymmetrized molecular dynamics (AMD). This is done by increasing the number of basic states in the AMD wave function, introducing a Skyrme-type delta-nucleon potential, and including $NN\leftrightarrow N\Delta$ reactions in the collision description. As a test of the delta dynamics, the extended AMD is applied to (p,p$'$) recations at $E_{\rm lab}=800$ MeV for a $^{12}$C target. It is found that the ratio and the absolute values for delta peak and quasielastic peak (QEP) in the $^{12}$C(p,p$'$) reaction are reproduced for angles \Theta_{\rm lab} \agt 40^\circ, pointing to a correct treatment of the delta dynamics in the extended AMD. For forward angles the QEP is overestimated. The results of the AMD calculations are compared to one-step Monte Carlo (OSMC) calculations and a detailed analysis of multi-step and delta potential effects is given. As important side results we present a way to apply a Gallilei invariant theory for (N,N$'$) reactions up to $E_{\rm lab} \approx 800$ MeV which ensures approximate Lorentz invariance and we discuss how to fix the width parameter $\nu$ of the single particle momentum distribution for outgoing nucleons in the AMD calculation.Comment: 28 pages, revtex, 12 figures included, figures are also available upon request as postscript files from the authors (e-mail: [email protected]), submitted to Phys. Rev.

Inhibition of Ubc13-mediated ubiquitination by GPS2 regulates multiple stages of B cell development

Non-proteolytic ubiquitin signaling mediated by Lys63 ubiquitin chains plays a critical role in multiple pathways that are key to the development and activation of immune cells. Our previous work indicates that GPS2 (G-protein Pathway Suppressor 2) is a multifunctional protein regulating TNF signaling and lipid metabolism in the adipose tissue through modulation of Lys63 ubiquitination events. However, the full extent of GPS2-mediated regulation of ubiquitination and the underlying molecular mechanisms are unknown. Here, we report that GPS2 is required for restricting the activation of TLR and BCR signaling pathways and the AKT/FOXO1 pathway in immune cells based on direct inhibition of Ubc13 enzymatic activity. Relevance of this regulatory strategy is confirmed in vivo by B cell-targeted deletion of GPS2, resulting in developmental defects at multiple stages of B cell differentiation. Together, these findings reveal that GPS2 genomic and non-genomic functions are critical for the development and cellular homeostasis of B cells

Whole-genome analyses reveal genetic instability of Acetobacter pasteurianus

Acetobacter species have been used for brewing traditional vinegar and are known to have genetic instability. To clarify the mutability, Acetobacter pasteurianus NBRC 3283, which forms a multi-phenotype cell complex, was subjected to genome DNA sequencing. The genome analysis revealed that there are more than 280 transposons and five genes with hyper-mutable tandem repeats as common features in the genome consisting of a 2.9-Mb chromosome and six plasmids. There were three single nucleotide mutations and five transposon insertions in 32 isolates from the cell complex. The A. pasteurianus hyper-mutability was applied for breeding a temperature-resistant strain grown at an unviable high-temperature (42°C). The genomic DNA sequence of a heritable mutant showing temperature resistance was analyzed by mutation mapping, illustrating that a 92-kb deletion and three single nucleotide mutations occurred in the genome during the adaptation. Alpha-proteobacteria including A. pasteurianus consists of many intracellular symbionts and parasites, and their genomes show increased evolution rates and intensive genome reduction. However, A. pasteurianus is assumed to be a free-living bacterium, it may have the potentiality to evolve to fit in natural niches of seasonal fruits and flowers with other organisms, such as yeasts and lactic acid bacteria

Traveling Waves in One-Dimensional Electroconvection of Nematic Liquid Crystals

We report ac-driven electroconvection (EC) of nematic liquid crystals (NLCs) in one-dimensional cells employing an in-plane switching mode. The dynamical features of traveling waves (TWs), such as their velocity and the change in their propagating direction, are examined by varying the ac voltage V and frequency f. In particular, two-mode TWs are discovered; one showing a larger amplitude and a lower velocity arises, evolves, and vanishes randomly in time and space, while the other showing a smaller amplitude and a higher velocity moves continuously; the former appears to be a secondary wave that originates from an unknown instability. Moreover, the change in TW directions is found through turbulence causing disclinations of the director field of NLCs. Evidently, the disclinations play a role as a source or a sink of TWs