1. Olanzapine treatment effectively relieves breakthrough ...
1 aug 2023 · In a pivotal randomized controlled study of 380 patients undergoing HEC, the addition of olanzapine to the standard three-drug regimen, ...
Olanzapine treatment prevents chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy (HEC). However, its role in the secondary prevention of breakthrough CINV in real-world cancer care should be further evaluated. We conducted a retrospective study on patients receiving olanzapine to prevent breakthrough CINV refractory to standard antiemetic therapy. The major outcome was improvement in CINV, defined as any downgrade in CINV symptoms, according to the Common Terminology Criteria for Adverse Events. Comprete response was defined as no symptoms in CINV, i.e., Grade 0. These outcomes were compared in the HEC versus non-HEC groups and the standard- (5 or 10 mg/day) versus low- (2.5 mg/day) dose groups. The other outcome measurement was adverse events (AEs). We analyzed 127 patients, including 92 women, with a median age of 50 years (range: 19–89 years). Baseline CINV severity was grade 1, 2, and 3 in 18%, 69%, and 13% of the patients, respectively. After prophylaxis with olanzapine at doses of 2.5, 5, or 10 mg/day, improvement was observed in 105 (83%) patients, with a complete response in 42 patients (33%). The improvement and complete remission rates for the HEC (n = 96) and non-HEC (n = 31) groups were 86% and 71% (p = 0.048) versus 38% and 19% (p = 0.062), respectively. The rates for the standard- (n = 98) and low- (n = 29) dose groups were 86% and 82% (p = 0.568) versus 28% and 52% (p = 0.015), respectively. Thirt...
2. Effects of fenofibrate and its combination with lovastatin on the ...
... can cause impairment in lipid control, besides alimentary intake (diabetes mellitus, chronic kidney disease, drugs and alcohol abuse) (Qi et al., 2012 ...
Fibrates and statins have been widely used to reduce triglyceride and cholesterol levels, respectively. Besides its lipid-lowering effect, the side ef …
3. PGC-1α-Mediated Branched-Chain Amino Acid Metabolism in ... - PLOS
... Shinji Miura [ view less ]. Yukino Hatazawa. Contributed equally to this work ... After drug selection, virally infected stable cells were cultured to ...
Peroxisome proliferator-activated receptor (PPAR) γ coactivator 1α (PGC-1α) is a coactivator of various nuclear receptors and other transcription factors, which is involved in the regulation of energy metabolism, thermogenesis, and other biological processes that control phenotypic characteristics of various organ systems including skeletal muscle. PGC-1α in skeletal muscle is considered to be involved in contractile protein function, mitochondrial function, metabolic regulation, intracellular signaling, and transcriptional responses. Branched-chain amino acid (BCAA) metabolism mainly occurs in skeletal muscle mitochondria, and enzymes related to BCAA metabolism are increased by exercise. Using murine skeletal muscle overexpressing PGC-1α and cultured cells, we investigated whether PGC-1α stimulates BCAA metabolism by increasing the expression of enzymes involved in BCAA metabolism. Transgenic mice overexpressing PGC-1α specifically in the skeletal muscle had increased the expression of branched-chain aminotransferase (BCAT) 2, branched-chain α-keto acid dehydrogenase (BCKDH), which catabolize BCAA. The expression of BCKDH kinase (BCKDK), which phosphorylates BCKDH and suppresses its enzymatic activity, was unchanged. The amount of BCAA in the skeletal muscle was significantly decreased in the transgenic mice compared with that in the wild-type mice. The amount of glutamic acid, a metabolite of BCAA catabolism, was increased in the transgenic mice, suggesting the activation o...
4. Analysis of Choriocapillaris Flow Patterns by Continuous Laser ...
Yuya Hirata; Hirokazu Nishiwaki; Shinji Miura; Yoshiaki Ieki; Yoshihito ... A potential method for local drug and dye delivery in the ocular vasculature.
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5. [PDF] Adverse Events Associated With New Injectable-Free Multidrug-Resistant ...
Huynh J, Marais BJ. Multidrug-resistant tuberculosis infection and disease in children: a review of new and repurposed drugs. Ther Adv Infect Dis. 2019;6 ...
6. Challenging Innovations in Synthetic Chemistry － Osaka University
Additionally, Professor Miura has shattered the common knowledge that ... It was only for a short period, but the basic knowledge of drug synthesis he ...
In order to develop and popularize cross-coupling reactions as environment-conscious industrial technology, problems such as raising efficiency, reducing waste products, and the simplification of the reaction process remain as unsolved issues. In Distinguished Professor Miura’s laboratory, a new method was developed in which the reaction process was advanced without any halogenation or metallization. Because the process is now able to be progressed without many intermediate steps, the process was shortened and the target molecules can be synthesized all at once. In addition, synthesis of molecule groups that had been difficult to construct has become possible.
7. PRC2-Mediated Apoptosis Evasion Is a Therapeutic Target of MDS/AML ...
10 dec 2023 · ... Shinji Tsutsumi, PhD4*, Takayuki Sakuma, MD1*, Takuma Ohashi, MD1 ... drugs. Apoptosis analysis revealed that valemetostat and ...
Program: Oral and Poster Abstracts Session: 604. Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Poster II Hematology Disease Topics & Pathways:Research, MDS, Acute Myeloid Malignancies, AML, Translational Research, Chronic Myeloid Malignancies, Diseases, Myeloid Malignancies
8. DNA Polymerases as Targets of Anticancer Nucleosides
... Drug Discovery (Discontinued) Currently Available Drugs for the Treatment of Obesity: Sibutramine and Orlistat Mini-Reviews in Medicinal Chemistry Anti ...
DNA polymerase is one of the most important target molecules of antitumor agents, especially for antimetabolite nucleosides that include 1-β-D-arabinofuranosylcytosine (araC) and 2-deoxy-2,2-difluorocytidine (gemcitabine). There are several subtypes of mammalian DNA polymerases and their localization and function have been clarified. DNA polymerase α, δ and ε have been implicated to be responsible for DNA replication, whereas DNA polymerase β, δ and e have been suggested to work in DNA repair. DNA polymerase γ is encoded in the nucleus but localizes in the mitochondria, and is responsible for the mitochondrial DNA replication. Recently, several antiviral nucleoside analogs were reported to inhibit DNA polymerase g after intracellular phosphorylation and cause severe chronic toxicity. 1-(2-Deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine (4-thio-FAC), an antimetabolite similar to araC and gemcitabine, is recently shown by us to be a very promising agent because of its potent antitumor activity by oral administration to mice. We tested for the inhibitory activities of the triphosphates of 4-thio-FAC and gemcitabine against DNA polymerase α, β and γ. The triphosphates of 4-thio-FAC (4-thio-FACTP) exhibited the potent inhibitory action against DNA polymerase a, whereas it showed moderate inhibition against DNA polymerase β and little inhibition against DNA polymerase γ. The triphosphate of gemcitabine (dFdCTP) did not show potent inhibition against these three DNA polymera...
9. Faculty Profiles - OHASHI, Koji
... Shinji Miura, Toyoaki Murohara, Noriyuki Ouchi ... Activated factor X (FXa) inhibitors are safe and first-line drugs for the prevention of thrombosis in patients ...
Myonectin protects against skeletal muscle dysfunction in male mice through activation of AMPK/PGC1α pathway. International journal
10. Trophoblast stem cell-based organoid models of the human placental barrier
8 feb 2024 · The quantitative analysis of transplacental passages of chemicals is crucial in drug development since maternally circulating drugs can result ...
Human placental villi have essential roles in producing hormones, mediating nutrient and waste exchange, and protecting the fetus from exposure to xenobiotics. Human trophoblast organoids that recapitulate the structure of villi could provide an important in vitro tool to understand placental development and the transplacental passage of xenobiotics. However, such organoids do not currently exist. Here we describe the generation of trophoblast organoids using human trophoblast stem (TS) cells. Following treatment with three kinds of culture medium, TS cells form spherical organoids with a single outer layer of syncytiotrophoblast (ST) cells that display a barrier function. Furthermore, we develop a column-type ST barrier model based on the culture condition of the trophoblast organoids. The bottom membrane of the column is almost entirely covered with syndecan 1-positive ST cells. The barrier integrity and maturation levels of the model are confirmed by measuring transepithelial/transendothelial electrical resistance (TEER) and the amount of human chorionic gonadotropin. Further analysis reveals that the model can be used to derive the apparent permeability coefficients of model compounds. In addition to providing a suite of tools for the study of placental development, our trophoblast models allow the evaluation of compound transfer and toxicity, which will facilitate drug development. The placenta is a transient organ that regulates the fetal environment, but our understand...
