Drug Repositioning for Gynecologic Tumors: A New Therapeutic Strategy for Cancer

The goals of drug repositioning are to find a new pharmacological effect of a drug for which human safety and pharmacokinetics are established and to expand the therapeutic range of the drug to another disease. Such drug discovery can be performed at low cost and in the short term based on the results of previous clinical trials. New drugs for gynecologic tumors may be found by drug repositioning. For example, PPAR ligands may be effective against ovarian cancer, since PPAR activation eliminates COX-2 expression, arrests the cell cycle, and induces apoptosis. Metformin, an antidiabetic drug, is effective for endometrial cancer through inhibition of the PI3K-Akt-mTOR pathway by activating LKB1-AMPK and reduction of insulin and insulin-like growth factor-1 due to AMPK activation. COX-2 inhibitors for cervical cancer may also be examples of drug repositioning. PGE2 is induced in the arachidonate cascade by COX-2. PGE2 maintains high expression of COX-2 and induces angiogenic factors including VEGF and bFGF, causing carcinogenesis. COX-2 inhibitors suppress these actions and inhibit carcinogenesis. Combination therapy using drugs found by drug repositioning and current anticancer drugs may increase efficacy and reduce adverse drug reactions. Thus, drug repositioning may become a key approach for gynecologic cancer in drug discovery

MicroRNAs in endometrial cancer

Endometrial cancer is a common malignant gynecological tumor, but there are few biomarkers that are useful for early and accurate diagnosis and few treatments other than surgery. However, use of microRNAs (miRNAs) that induces gene downregulation in cells may permit effective and minimally invasive diagnosis and treatment. In endometrial cancer cells, expression levels of miRNAs including miR-185, miR-210 and miR-423 are upregulated and those of miR-let7e, miR-30c and miR-221 are downregulated compared to normal tissues, and these miRNAs are involved in carcinogenesis, invasion and metastasis. miRNAs with expression changes such as miR-181b, miR-324-3p and miR-518b may be used as prognostic biomarkers and transfection of miR-152 may inhibit cancer growth. However, most current studies of miRNAs are at a basic level and further work is needed to establish clinical applications targeting miRNAs

Anionic ordering in Pb₂Ti₄O₉F₂ revisited by nuclear magnetic resonance and density functional theory

複合アニオン材料の構造決定における実験と計算の融合的アプローチ. 京都大学プレスリリース. 2022-10-31.A combination of 19F magic angle spinning (MAS) nuclear magnetic resonance (NMR) and density functional theory (DFT) were used to study the ordering of F atoms in Pb₂Ti₄O₉F₂. This analysis revealed that F atoms predominantly occupy two of the six available inequivalent sites in a ratio of 73 : 27. DFT-based calculations explained the preference of F occupation on these sites and quantitatively reproduced the experimental occupation ratio, independent of the choice of functional. We concluded that the Pb atom's 6s2 lone pair may play a role (∼0.1 eV per f.u.) in determining the majority and minority F occupation sites with partial density of states and crystal orbital Hamiltonian population analyses applied to the DFT wave functions

Anionic ordering in Pb₂Ti₄O₉F₂ revisited by nuclear magnetic resonance and density functional theory

複合アニオン材料の構造決定における実験と計算の融合的アプローチ. 京都大学プレスリリース. 2022-10-31.A combination of 19F magic angle spinning (MAS) nuclear magnetic resonance (NMR) and density functional theory (DFT) were used to study the ordering of F atoms in Pb₂Ti₄O₉F₂. This analysis revealed that F atoms predominantly occupy two of the six available inequivalent sites in a ratio of 73 : 27. DFT-based calculations explained the preference of F occupation on these sites and quantitatively reproduced the experimental occupation ratio, independent of the choice of functional. We concluded that the Pb atom's 6s2 lone pair may play a role (∼0.1 eV per f.u.) in determining the majority and minority F occupation sites with partial density of states and crystal orbital Hamiltonian population analyses applied to the DFT wave functions

Treatment for secondary hyperparathyroidism focusing on parathyroidectomy

Secondary hyperparathyroidism (SHPT) is a major problem for patients with chronic kidney disease and can cause many complications, including osteodystrophy, fractures, and cardiovascular diseases. Treatment for SHPT has changed radically with the advent of calcimimetics; however, parathyroidectomy (PTx) remains one of the most important treatments. For successful PTx, removing all parathyroid glands (PTGs) without complications is essential to prevent persistent or recurrent SHPT. Preoperative imaging studies for the localization of PTGs, such as ultrasonography, computed tomography, and 99mTc-Sestamibi scintigraphy, and intraoperative evaluation methods to confirm the removal of all PTGs, including, intraoperative intact parathyroid hormone monitoring and frozen section diagnosis, are useful. Functional and anatomical preservation of the recurrent laryngeal nerves can be confirmed via intraoperative nerve monitoring. Total or subtotal PTx with or without transcervical thymectomy and autotransplantation can also be performed. Appropriate operative methods for PTx should be selected according to the patients’ need for kidney transplantation. In the case of persistent or recurrent SHPT after the initial PTx, localization of the causative PTGs with autotransplantation is challenging as causative PTGs can exist in the neck, mediastinum, or autotransplanted areas. Additionally, the efficacy and cost-effectiveness of calcimimetics and PTx are increasingly being discussed. In this review, medical and surgical treatments for SHPT are described

Subaru Hyper Suprime-Cam Survey for An Optical Counterpart of GW170817

We perform a $z$-band survey for an optical counterpart of a binary neutron star coalescence GW170817 with Subaru/Hyper Suprime-Cam. Our untargeted transient search covers $23.6$ deg$^2$ corresponding to the $56.6\%$ credible region of GW170817 and reaches the $50\%$ completeness magnitude of $20.6$ mag on average. As a result, we find 60 candidates of extragalactic transients, including J-GEM17btc (a.k.a. SSS17a/DLT17ck). While J-GEM17btc is associated with NGC 4993 that is firmly located inside the 3D skymap of GW170817, the other 59 candidates do not have distance information in the GLADE v2 catalog or NASA/IPAC Extragalactic Database (NED). Among 59 candidates, 58 are located at the center of extended objects in the Pan-STARRS1 catalog, while one candidate has an offset. We present location, $z$-band apparent magnitude, and time variability of the candidates and evaluate the probabilities that they are located inside of the 3D skymap of GW170817. The probability for J-GEM17btc is $64\%$ being much higher than those for the other 59 candidates ($9.3\times10^{-3}-2.1\times10^{-1}\%$). Furthermore, the possibility, that at least one of the other 59 candidates is located within the 3D skymap, is only $3.2\%$. Therefore, we conclude that J-GEM17btc is the most-likely and distinguished candidate as the optical counterpart of GW170817.Comment: 14 pages, 9 figures. Accepted for publication in PASJ (Publications of the Astronomical Society of Japan

Discovery of the Fastest Early Optical Emission from Overluminous SN Ia 2020hvf: A Thermonuclear Explosion within a Dense Circumstellar Environment

Ia型超新星の爆発直後の閃光を捉えることに成功 --特異な爆発に至る恒星進化の謎に迫る--. 京都大学プレスリリース. 2021-12-10.In this Letter we report a discovery of a prominent flash of a peculiar overluminous Type Ia supernova, SN 2020hvf, in about 5 hr of the supernova explosion by the first wide-field mosaic CMOS sensor imager, the Tomo-e Gozen Camera. The fast evolution of the early flash was captured by intensive intranight observations via the Tomo-e Gozen high-cadence survey. Numerical simulations show that such a prominent and fast early emission is most likely generated from an interaction between 0.01 M⊙ circumstellar material (CSM) extending to a distance of ∼10¹³ cm and supernova ejecta soon after the explosion, indicating a confined dense CSM formation at the final evolution stage of the progenitor of SN 2020hvf. Based on the CSM–ejecta interaction-induced early flash, the overluminous light curve, and the high ejecta velocity of SN 2020hvf, we suggest that the SN 2020hvf may originate from a thermonuclear explosion of a super-Chandrasekhar-mass white dwarf (“super-MCh WD”). Systematical investigations on explosion mechanisms and hydrodynamic simulations of the super-MCh WD explosion are required to further test the suggested scenario and understand the progenitor of this peculiar supernova

Intermediate-luminosity Type IIP SN 2021gmj: a low-energy explosion with signatures of circumstellar material

We present photometric, spectroscopic and polarimetric observations of the intermediate-luminosity Type IIP supernova (SN) 2021gmj from 1 to 386 days after the explosion. The peak absolute V-band magnitude of SN 2021gmj is -15.5 mag, which is fainter than that of normal Type IIP SNe. The spectral evolution of SN 2021gmj resembles that of other sub-luminous supernovae: the optical spectra show narrow P-Cygni profiles, indicating a low expansion velocity. We estimate the progenitor mass to be about 12 Msun from the nebular spectrum and the 56Ni mass to be about 0.02 Msun from the bolometric light curve. We also derive the explosion energy to be about 3 x 10^{50} erg by comparing numerical light curve models with the observed light curves. Polarization in the plateau phase is not very large, suggesting nearly spherical outer envelope. The early photometric observations capture the rapid rise of the light curve, which is likely due to the interaction with a circumstellar material (CSM). The broad emission feature formed by highly-ionized lines on top of a blue continuum in the earliest spectrum gives further indication of the CSM at the vicinity of the progenitor. Our work suggests that a relatively low-mass progenitor of an intermediate-luminosity Type IIP SN can also experience an enhanced mass loss just before the explosion, as suggested for normal Type IIP SNe.Comment: 18 pages, 16 figures, resubmitted to MNRAS after addressing referee comment