Aberrant Glycogen Synthase Kinase 3β Is Involved in Pancreatic Cancer Cell Invasion and Resistance to Therapy

Background and Purpose: The major obstacles to treatment of pancreatic cancer are the highly invasive capacity and resistance to chemo- and radiotherapy. Glycogen synthase kinase 3β (GSK3β) regulates multiple cellular pathways and is implicated in various diseases including cancer. Here we investigate a pathological role for GSK3β in the invasive and treatment resistant phenotype of pancreatic cancer. Methods: Pancreatic cancer cells were examined for GSK3β expression, phosphorylation and activity using Western blotting and in vitro kinase assay. The effects of GSK3β inhibition on cancer cell survival, proliferation, invasive ability and susceptibility to gemcitabine and radiation were examined following treatment with a pharmacological inhibitor or by RNA interference. Effects of GSK3β inhibition on cancer cell xenografts were also examined. Results: Pancreatic cancer cells showed higher expression and activity of GSK3β than non-neoplastic cells, which were associated with changes in its differential phosphorylation. Inhibition of GSK3β significantly reduced the proliferation and survival of cancer cells, sensitized them to gemcitabine and ionizing radiation, and attenuated their migration and invasion. These effects were associated with decreases in cyclin D1 expression and Rb phosphorylation. Inhibition of GSK3β also altered the subcellular localization of Rac1 and F-actin and the cellular microarchitecture, including lamellipodia. Coincident with these changes were the reduced secretion of matrix metalloproteinase-2 (MMP-2) and decreased phosphorylation of focal adhesion kinase (FAK). The effects of GSK3β inhibition on tumor invasion, susceptibility to gemcitabine, MMP-2 expression and FAK phosphorylation were observed in tumor xenografts. Conclusion: The targeting of GSK3β represents an effective strategy to overcome the dual challenges of invasiveness and treatment resistance in pancreatic cancer. © 2013 Kitano et al

A Clinical Trial Evaluating the Usefulness of Tailored Antimicrobial Prophylaxis Using Rectal-culture Screening Media Prior to Transrectal Prostate Biopsy: A Multicenter, Randomized Controlled Trial

The aim of this report is to introduce an on-going, multicenter, randomized controlled trial to evaluate whether tailored antimicrobial prophylaxis guided by rectal culture screening prevents acute bacterial prostatitis following transrectal prostate biopsy (TRPB). Patients will be randomized into an intervention or non-intervention group; tazobactam-piperacillin or levofloxacin will be prophylactically administered according to the results of rectal culture prior to TRPB in the intervention group whereas levofloxacin will be routinely given in the non-intervention group. The primary endpoint is the occurrence rate of acute bacterial prostatitis after TRPB. Recruitment begins in April, 2021 and the target total sample size is 5,100 participants

HISTOPATHOLOGICAL STUDY OF ENDOCHONDRAL OSSIFICATION OF FEMUR IN INFANTS Histological Observation on 193 Autopsy Cases

The purpose of the present study was to clarify the fundamental histological changes in endochondral ossification and their morphogenesis in 190 infants with various kinds of diseases ranging in ages from birth to 14 months and in 3 aborted fetuses. Histopathological examination was performed on the epiphyseal plate and its precursor, that is, the diaphyseal growing part of the cartilaginous epiphysis at the lower end of the femur. Before the development of the secondary ossification center, the diaphyseal growing part showed a less distinct zonal differentiation in structure. With the progressive development of the secondary ossification center, the epiphyseal plate became well differentiated and showed a typical zonal differentiation. The cluster pattern of the proliferating cartilage cells was characteristic in the fetal life. There was a close relationship between the cluster pattern and the insufficient development of the secondary ossification center. The present study revealed that the cluster pattern, disturbances in the proliferation of the cartilage cells and calcification of the cartilage were most fundamental and influential in morphogenesis of the histological changes in the endochondral ossification in the younger infants

Role of QCD in moduli stabilization during inflation and axion dark matter

Abstract Ignorance of the initial condition for the axion dynamics in the early Universe has led us to consider an O(1) valued initial amplitude, and that prefers the decay constant, F a , of the QCD axion to be an intermediate scale such as 1012 GeV in order to explain the dark matter abundance. We explore a cosmological scenario of F a being much larger than 1012 GeV by considering the axion and modulus dynamics during inflation to set the initial amplitude. We show that if the volume modulus (radion) of the extra-dimension is stabilized mainly by the QCD contribution to the modulus potential during inflation, the QCD axion with the string-scale decay constant obtains a mass around the inflationary Hubble parameter. This means that the axion rolls down to the θ = 0 minimum during the inflation realizing almost vanishing initial amplitude, and the inflationary quantum fluctuation can be the dominant source of the current number density of axions. We find natural parameter regions where the axion explains the cold dark matter of the Universe, while the constraint on the isocurvature perturbation is avoided. The presence of the axion miniclusters or axion stars are predicted in a wide range of parameters, including the one explains the Subaru-HCS microlensing event

Juvenile angiofibroma of the maxillary sinus. A case report

The clinicopathological features of a rare case of juvenile angiofibroma originating from the maxillary sinus of a 13-year-old boy are reported. This tumor was composed of angiomatous and fibrous structures. The analysis of nucleolar organizer regions (NOR) of the various components of this tumor indicated that the fundamental elements were the fibroblastic cells, rather than the vascular endothelial cells.</p