著者

Takaomi Kasuga Asako Sato Tetsuya Babazono

出版者

Society of Tokyo Women's Medical University

雑誌

Tokyo Women's Medical University Journal (ISSN:24326186)

巻号頁・発行日

pp.2022015, (Released:2023-04-27)

参考文献数

30

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Background: Aortic valve calcification (AVC) has a strong association with cardiovascular outcomes in patients with type 2 diabetics (T2D). The objective of this study was to determine the prevalence and risk factors for AVC in Japanese T2D.Methods: We conducted a cross-sectional study of 193 consecutive T2D with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 and without overt heart disease (110 men, mean age 61 years). AVC was determined as bright echoes > 1 mm on at least one cusp of the aortic valve by echocardiography.Results: Eighty-two (42%) diabetic patients had AVC, 9 patients had aortic valve stenosis, and 25 had regurgitation. Patients with AVC were older (67 vs. 55 years), with longer diabetic duration (15 vs. 11 years), lower HbA1c (9.1 vs. 10.0%), higher presence of diabetic retinopathy (66 vs. 47%), lower BMI (24 vs. 26 kg/m2), and lower eGFR (82.1 vs. 90.4 mL/min/1.73 m2) (p < 0.01) than patients without AVC. By logistic regression analysis, older age (p < 0.001) and presence of diabetic retinopathy (p < 0.05) were independent risk factors for AVC in T2D.Conclusions: The prevalence of AVC was 42% in Japanese T2D. Diabetic retinopathy associates with presence of AVC.

著者

Junko Oya Tomoko Nakagami Yuichiro Kondo Aki Katamine Mika Shimizu Yukiko Hasegawa Tetsuya Babazono

出版者

Society of Tokyo Women's Medical University

雑誌

Tokyo Women's Medical University Journal (ISSN:24326186)

巻号頁・発行日

pp.2023008, (Released:2023-11-15)

参考文献数

29

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Background: To compare the efficacy and safety of pemafibrate with those of fenofibrate in a real-world setting in patients with hypertriglyceridemia and type 2 diabetes (T2D).Methods: This study included 155 patients with hypertriglyceridemia (>175 mg/dL) and T2D. Adjusted least square mean changes in the serum levels of triglycerides (TG), transaminases, γ-glutamyl transpeptidase (γGTP), and estimated glomerular filtration rates (eGFRs) were compared before and after a 3-month therapy with pemafibrate (0.2 mg), fenofibrate (160 mg), or bezafibrate (400 mg). Multivariate logistic regression analyses were performed to examine the association between fibrates, achievement of target TG levels, and deterioration of liver and renal function.Results: Pemafibrate therapy greatly reduced TG levels, which was three times better than fenofibrate therapy in achieving the target range for TG levels. The administration of pemafibrate, not fenofibrate, was significantly associated with a lower risk of increasing γGTP levels. Similarly, a lower risk of eGFR reduction was observed in the pemafibrate group than in the fenofibrate group.Conclusions: Pemafibrate achieved a greater reduction in TG levels toward the desired target range than did fenofibrate. Moreover, pemafibrate was associated with a lower risk profile for elevated γGTP and reduced eGFR than fenofibrate.

著者

Hidekazu Kuramochi

出版者

Society of Tokyo Women's Medical University

雑誌

Tokyo Women's Medical University Journal (ISSN:24326186)

巻号頁・発行日

pp.2023004, (Released:2023-07-21)

参考文献数

19

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Recent advances in molecular biology have led to the identification of molecules associated with carcinogenesis and the development of molecular-targeted drugs that selectively attack qualitative or quantitative molecular changes in cancer cells. Molecular targeted drugs are classified into "low molecular weight compounds" and "monoclonal antibody drugs" according to the difference in molecular weight. Molecular targeted drugs often have clinically meaningful biomarkers, such as gain- or loss-of-function in cancer-related target genes caused by point mutations, amplification, fusion, and deletion. High therapeutic effects can be expected by detecting driver mutations, which are directly related to carcinogenesis, and by using the corresponding molecular-targeted drugs. In recent years, the development of next-generation sequencing has enabled the simultaneous measurement of hundreds of gene sequences, and an oncogene panel containing cancer-related genes has been covered by the National Health Insurance. Precision medicine is defined as medical care designed to optimize the efficiency or therapeutic benefit for specific patient groups, especially using genetic or molecular profiling.This article is based on a study reported in the Journal of Tokyo Women's Medical University (in Japanese) 2022;92 (1):1-7.

著者

Junko Tahara

出版者

Society of Tokyo Women's Medical University

雑誌

Tokyo Women's Medical University Journal (ISSN:24326186)

巻号頁・発行日

pp.2023002, (Released:2023-06-22)

参考文献数

15

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Molecularly targeted drugs affect various molecules associated with cancer cell progression, infiltration, and metastasis. Recent advances in molecular biology have identified molecules associated with cancer and inflammatory disease, leading to the development of new molecularly targeted drugs. Unlike cytotoxic anticancer agents, molecularly targeted drugs act on cancer-specific molecules and cause less damage to normal cells. Consequently, there are fewer adverse events associated with molecularly targeted drugs. These advances in drug development promise novel and effective treatments for gastroenterological diseases.This article is based on a study first reported in the Journal of Tokyo Women's Medical University (in Japanese), 2022; 92 (5):153-7.

著者

Kazuhiko Yoshida

出版者

Society of Tokyo Women's Medical University

雑誌

Tokyo Women's Medical University Journal (ISSN:24326186)

巻号頁・発行日

pp.2023001, (Released:2023-04-27)

参考文献数

27

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In recent years, various molecular-targeted therapies have been developed and clinically introduced. Molecular targeted therapies for advanced cancers have also been approved in the field of urology. The efficacy of various molecular-targeted drug-related therapies has been established, particularly for renal cell carcinoma (RCC). In Japan, six types of multi-kinase inhibitors, including receptor tyrosine kinases, two types of mammalian target of rapamycin inhibitors, and four types of immune checkpoint inhibitors, such as anti-programmed death-1 (PD-1), cytotoxic T-lymphocyte antigen 4, and PD-ligand 1 (L1), are currently being used for the treatment of advanced RCC.For urothelial cancers, anti-PD-1 antibodies as second-line treatment and anti-PD-L1 antibodies as maintenance therapy after chemotherapy have been approved for insurance coverage in Japan. For advanced prostate cancer, the anti-PD-1 antibody is indicated for microsatellite instability-high cases. Poly (ADP-ribose) polymerase (PARP) inhibitors can be used for patients with castration-resistant prostate cancer who are positive for BRCA gene mutations.It is important to consider patient, tumor, and drug characteristics when selecting appropriate treatments for advanced urological cancers. This article describes molecular-targeted drug therapies for advanced RCC that are frequently used in Japan.

著者

Ayako Nakamura-Ishizu Fumio Nakamura

出版者

Society of Tokyo Women's Medical University

雑誌

Tokyo Women's Medical University Journal (ISSN:24326186)

巻号頁・発行日

pp.2021003, (Released:2021-07-12)

参考文献数

58

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Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has a wide range of clinical manifestations, including acute respiratory distress syndrome, severe inflammation, abnormal blood coagulation, and cytokine storm syndrome. SARS-CoV-2 uniquely facilitates its entry and expansion in host cells through the spike protein consisting of S1 (receptor binding domain) and S2 (fusion peptide domain). The S1 binds to angiotensin-converting enzyme 2 (ACE2), the host cell receptor. The cleavage at the boundary of S1 and S2 by Furin protease and subsequent digestion within the S2 by TMPRSS2 activate the S2 fusion peptides, which are necessary for the entry of SARS-CoV-2 into host cells. After infection, SARS-CoV-2 RNA genome encodes viral proteins including structural proteins, RNA polymerases/helicases, and modulators of host- defense system, which inhibit type I interferon-related immune signaling and signal transducer and activator of transcription 1 (STAT1) signaling. In contrast, SARS-CoV-2 infection activates the proinflammatory cytokines, such as interleukin 6 (IL-6) and tumor necrosis factor α (TNFα). In severe cases of COVID-19, these alterations in immune signaling may induce a state of systemic immune dysfunction. Recent studies also revealed the involvement of hematopoietic cells and alteration of cellular metabolic state in COVID-19. We here review the pathogenesis of COVID-19, primarily focusing on the molecular mechanism underlying SARS-CoV-2 infection and the resulting immunological and hematological alterations.

著者

Hidehito Kato Naoko Yanagisawa

出版者

Society of Tokyo Women's Medical University

雑誌

Tokyo Women's Medical University Journal (ISSN:24326186)

巻号頁・発行日

pp.2021001, (Released:2021-06-10)

参考文献数

52

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Viruses require the host cellular machinery for protein translation and replication. Upon proliferation, virions damage cells and are released from the infected cells before infecting other cells. Acute inflammation occurs when host cells are damaged by infection. The cell receptors to which severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) binds, are widely distributed compared to those for other viruses, thereby resulting in various symptoms such as rhinitis, pneumonia, and enteritis. In general, RNA viruses, including SARS-CoV-2, exhibit a high frequency of gene mutations. Antigenic modulation due to genetic mutations of the spike protein causes cytokine storms because of strong activation of the innate immune system, similar to the phenomenon previously observed in highly pathogenic avian influenza. The proportion of severely ill patients due to coronavirus disease 2019 (COVID-19) varies from country to country, and factors that are responsible for the severity of the disease include antibody-dependent enhancement (ADE), Bacillus Calmette-Guérin (BCG) vaccination, and human leukocyte antigen (HLA) type. ADE and HLA types may also influence the protective effect of immunity, including its vaccine response against SARS-CoV-2.This report is a secondary publication of our previous review report "Tokyo Wom Med Univ 91: 2-10, 2021."