47 research outputs found
Computer-assisted Minimally Invasive Posterior Lumbar Interbody Fusion without C-arm Fluoroscopy
Computer-assisted spinal surgery is becoming more common; however, this is the first technical report to describe the technique of minimally invasive spinal posterior lumbar interbody fusion (MIS-PLIF) without using C-arm fluoroscopy. The authors report 2 years of follow-up of a 49-year-old female patient with L4 degenerative spondylolisthesis. The patient suffered from low back pain and intermittent claudication for more than 6 years. The authors performed computer-assisted MIS-PLIF without C-arm fluoroscopy. Instead, O-arm® navigation, the use of which reduces radiation exposure to patients as well as others in the operating room, was employed. Surgery was successful, and correct lumbar alignment was maintained. She had neither neurological deficits nor low back pain at her 12-month final follow-up. In conclusion, computer-assisted MIS-PLIF without C-arm fluoroscopy is a useful technique that reduces radiation exposure to the surgeon and operating room staff
Age-specific serum anti-Müllerian hormone concentration in Japanese women and its usefulness as a predictor of the ovarian response
Purpose: To compare the ovarian response predictive ability of anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), and estradiol (E2) and to determine the age-specific distribution of serum AMH concentrations of Japanese women.
Methods: This was a multicenter (four-site), observational, analytic, cross-sectional Japanese study consisting of two parts: Study 1 (the prediction of the ovarian response of 236 participants who were undergoing controlled ovarian stimulation [COS]) and Study 2 (the distribution of the AMH concentration with an assay of 417 healthy women who were aged 20-49 years and who had normal menstrual cycles).
Results: The AMH had a significantly higher predictive value for the normal and high responders than FSH and E2 as a stronger correlation between the ovarian response and AMH was observed than for FSH and E2. The serum AMH concentration decreased proportionally with age.
Conclusion: The AMH concentration correlated well with the oocyte count in the patients who were undergoing COS for in vitro fertilization and was shown to predict the risk of ovarian hyperstimulation syndrome among these patients
Drug repositioning of tranilast to sensitize a cancer therapy by targeting cancer-associated fibroblast
Cancer-associated fibroblasts (CAFs) are a major component of the tumor microenvironment that mediate resistance of cancer cells to anticancer drugs. Tranilast is an antiallergic drug that suppresses the release of cytokines from various inflammatory cells. In this study, we investigated the inhibitory effect of tranilast on the interactions between non-small cell lung cancer (NSCLC) cells and the CAFs in the tumor microenvironment. Three EGFR-mutant NSCLC cell lines, two KRAS-mutant cell lines, and three CAFs derived from NSCLC patients were used. To mimic the tumor microenvironment, the NSCLC cells were cocultured with the CAFs in vitro, and the molecular profiles and sensitivity to molecular targeted therapy were assessed. Crosstalk between NSCLC cells and CAFs induced multiple biological effects on the NSCLC cells both in vivo and in vitro, including activation of the STAT3 signaling pathway, promotion of xenograft tumor growth, induction of epithelial-mesenchymal transition (EMT), and acquisition of resistance to molecular-targeted therapy, including EGFR-mutant NSCLC cells to osimertinib and of KRAS-mutant NSCLC cells to selumetinib. Treatment with tranilast led to inhibition of IL-6 secretion from the CAFs, which, in turn, resulted in inhibition of CAF-induced phospho-STAT3 upregulation. Tranilast also inhibited CAF-induced EMT in the NSCLC cells. Finally, combined administration of tranilast with molecular-targeted therapy reversed the CAF-mediated resistance of the NSCLC cells to the molecular-targeted drugs, both in vitro and in vivo. Our results showed that combined administration of tranilast with molecular-targeted therapy is a possible new treatment strategy to overcome drug resistance caused by cancer-CAF interaction
Overcoming epithelial-mesenchymal transition-mediated drug resistance with monensin-based combined therapy in non-small cell lung cancer
Background
The epithelial-mesenchymal transition (EMT) is a key process in tumor progression and metastasis and is also associated with drug resistance. Thus, controlling EMT status is a research of interest to conquer the malignant tumors.
Materials and methods
A drug repositioning analysis of transcriptomic data from a public cell line database identified monensin, a widely used in veterinary medicine, as a candidate EMT inhibitor that suppresses the conversion of the EMT phenotype. Using TGF-β-induced EMT cell line models, the effects of monensin on the EMT status and EMT-mediated drug resistance were assessed.
Results
TGF-β treatment induced EMT in non-small cell lung cancer (NSCLC) cell lines and the EGFR-mutant NSCLC cell lines with TGF-β-induced EMT acquired resistance to EGFR-tyrosine kinase inhibitor. The addition of monensin effectively suppressed the TGF-β-induced-EMT conversion, and restored the growth inhibition and the induction of apoptosis by the EGFR-tyrosine kinase inhibitor.
Conclusion
Our data suggested that combined therapy with monensin might be a useful strategy for preventing EMT-mediated acquired drug resistance
Regulation of DNA nucleases by molecular crowding
Here, we examined the effects of molecular crowding on the function, structure and stability of nucleases. We found that the hydrolysis of a 29-mer double-stranded DNA by the endonucleases DNase I and S1 nuclease was substantially enhanced by molecular crowding using polyethylene glycol (PEG); however, molecular crowding had little effect on hydrolysis by exo III and exo I exonucleases. Moreover, kinetic analysis showed that the maximum velocity for the reaction of DNase I at 25°C was increased from 0.1 to 2.7 μM/min by molecular crowding with 20% (w/v) PEG, whereas that of exonuclease I at 37°C decreased from 2.2 to 0.4 μM/min. In contrast, molecular crowding did not significantly affect the Michaelis constant of DNase I or exonuclease I. These results indicate that molecular crowding has different effects on the catalytic activities of exonucleases and endonucleases
ケツエキ シッカン カンジャ ノ テツカジョウショウ ニ タイスル ヒョウカ ホウホウ ノ ケントウ MRI ニヨル ヒ シンシュウテキ テツリョウ テイリョウ ソクテイ
【背景】血液疾患では長期輸血等で鉄過剰となる。肝鉄量は鉄過剰の重要な指標であり、欧米では MRI によ る非侵襲的定量法が普及しつつあるが、日本では殆ど行われていない。【方法】Gandon らの論文に基づき、腹部 MRI をグラディエントエコー法(GRE)で撮影、肝臓(L)と脊筋(M)の信号強度比(LBackground: Iron overload is a major problem for patients with hematological diseases. Liver iron concentration (LIC) is an important marker of iron overload. LIC has been measured by MRI (Magnetic Resonance Imaging) instead of invasive hepatic biopsy in European countries, but not yet in Japan. Methods: LIC was measured by MRI according to Gandon\u27s method (Lancet 2004;363:357-362) using gradient echo sequence (GRE). Signal intensity ratio of the liver and muscle (L/M) was measured. LIC was estimated from the linear correlation curve of L/M and LIC shown in Gandon\u27s paper. LIC estimated from MRI (LIC-MRI) was compared with serological markers such as serum ferritin level. Patients:Three patients with hematological diseases (post-transfusion iron overload, chronic hemolytic anemia, secondary myelofibrosis) and three healthy persons as normal controls. Results: LIC-MRI and serological markers were normal among the three normal controls. Two patients showed ten times higher LIC-MRI and ferritin levels than normal ranges. Conclusion: LIC-MRI showed an excellent correlation with serum ferritin level. Because of low examination numbers for the present cases, further study is necessary
Studies of CdTe electrodeposition
The electrocrystallization and growth of Te and CdTe under potentiostatic conditions have been studied using the theories developed for the electrocrystallization of metals on foreign substrates. The electrodeposition of Te on glassy carbon and of CdTe on tin oxide coated glass take place by progressive nucleation/three dimensional growth under diffusion control, whereas the electrodeposition of CdTe on monocrystalline silicon takes place by instantaneous nucleation/two dimensional growth under kinetic control. From considerations of progressive nucleation/three dimensional growth under diffusion control, a new analytical equation to express increase in current with deposition time is proposed. The dependence of saturation nuclear number density on temperature is also discussed. Computer simulations of instantaneous nucleation/hemispherical growth under diffusion control have been carried out using the three dimensional diffusion limited aggregation technique. The simulated current transients are compared to analytical expressions. Photoeffects during electrodeposition have also been studied. The results show that the CdTe deposit behaves as an amorphous insulator with a high density of bandgap states.</p