Publications by authors named "Y Suzuki"

14,258 Publications

Molecular targeted drugs resistance impairs double-strand break repair and sensitizes ER-positive breast cancer to PARP inhibitors.

Breast Cancer 2021 Aug 3. Epub 2021 Aug 3.

Department of Molecular and Functional Dynamics, Graduate School of Medicine, Tohoku University, 2-1 Seoryo-machi, Aoba-ku, Sendai, 980-8575, Japan.

Background: There are various treatments for estrogen-positive breast cancer, mainly hormone therapy and molecular-targeted drugs. Acquiring resistance to these drugs is a major clinical problem. Additionally, little is known about the effect of drug resistance on the DNA repair mechanism. Poly ADP ribose polymerase (PARP) inhibitors currently used for treating HER2-negative metastatic breast cancer with BRCA mutations have been shown to be effective in BRCA-deficient cells with impaired homologous recombination repair. Here, we investigated the effect of drug resistance acquisition on the DNA repair mechanism and the effect of PARP inhibitors on ER (estrogen receptor) -positive breast cancer.

Methods: We investigated changes in the expression of DNA repair mechanism-related factors and repair ability of double-strand breaks (DSB) in various drug-resistant cell lines established in our laboratory. Additionally, PARP inhibitor susceptibility was investigated using olaparib.

Results: DSB repairs in MCF-7 and hormone therapy-resistant model cells were normal, and these cells demonstrated low sensitivity to olaparib. The resistant cell lines against CDK4/6 inhibitors, fulvestrant and mTOR/PI3K inhibitors showed decreased DSB repair ability and high olaparib sensitivity. They showed low sensitivity to CDK4/6 inhibitors, a close link between acquiring resistance to CDK4/6 inhibitors and hypersensitivity to olaparib.

Conclusions: Our study suggests some cases of acquiring drug resistance impairs DSB repair ability and sensitizes ER-positive breast cancer to PARP inhibitors.
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http://dx.doi.org/10.1007/s12282-021-01282-5DOI Listing
August 2021

Acute Liver Injury Due to T-cell Infiltration into the Liver as an Initial Clinical Finding of Adult T-cell Leukemia/Lymphoma.

Intern Med 2021 1;60(15):2431-2436. Epub 2021 Aug 1.

Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Japan.

Acute liver injury (ALI) has been rarely reported as a clinical finding of adult T-cell leukemia/lymphoma (ATLL). A 74-year-old Japanese female patient who was histologically diagnosed as having autoimmune hepatitis (AIH) one year earlier, showed elevations in her aminotransferase and total bilirubin levels, and this was considered to be an exacerbation of AIH. Liver biopsy revealed interface hepatitis. Because atypical lymphocytes and human T-cell leukemia virus 1 immunoglobulin G antibody were positive, the patient was diagnosed to have ATLL. The biopsy revealed CD4+ and CD8+, but not CD20+ lymphocytes. Thus, the ALI in the patient was due to T-cell infiltration into the liver, and not due to an exacerbation of AIH.
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http://dx.doi.org/10.2169/internalmedicine.6793-20DOI Listing
August 2021

Clinical and Serological Features and Pregnancy Outcomes in Women with Polymyositis/Dermatomyositis: A Case-based Review.

Intern Med 2021 Jul 30. Epub 2021 Jul 30.

Center for Rheumatic Diseases, Mie University Hospital, Japan.

We encountered a 30-year-old woman who developed dermatomyositis during pregnancy and was positive for anti-Mi-2 antibodies. She was successfully treated with prednisolone and tacrolimus and delivered a healthy child. We reviewed the cases of idiopathic inflammatory myositis (IIM) that developed during pregnancy that were published after the year 2000 to elucidate the profile of myositis-specific antibodies (MSAs) in them and to evaluate their obstetric outcomes. In cases with IIM that developed during pregnancy, anti-Mi-2, anti-TIF1-g, anti-Jo-1, and anti-EJ antibodies was detected in one case each. The obstetric outcomes of the IIM-complicated pregnancies were poor, especially when complicated with active maternal myositis. Further studies focusing on the possible causal relationships between MSAs and cases with IIM that developed during pregnancy are needed. For better obstetric outcomes, appropriate suppression of the maternal disease activity using immunosuppressants and vigilance regarding the patient's requirement of Caesarean section is important.
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http://dx.doi.org/10.2169/internalmedicine.7924-21DOI Listing
July 2021

Real-world data for golimumab treatment in patients with ulcerative colitis in Japan: interim analysis in post-marketing surveillance.

Intest Res 2021 Aug 4. Epub 2021 Aug 4.

Inflammatory Bowel Disease Center, Toho University Sakura Medical Center, Sakura, Japan.

Background/aims: Golimumab (GLM) is an anti-tumor necrosis factor-α drug approved for treating moderate-to-severe active ulcerative colitis (UC). A 52-week post-marketing surveillance (PMS) was initiated to evaluate its safety and effectiveness in patients with UC in Japan. We present an interim report of the ongoing PMS.

Methods: Patients received 200 mg of subcutaneous GLM at week 0, 100 mg at week 2, and 100 mg 4 weekly thereafter. The safety analysis set included 392 patients with UC, and the effectiveness analysis set 387 patients. Safety and effectiveness were assessed at week 6.

Results: Adverse drug reactions (ADRs) were reported in 8.2% (32/392) and serious ADRs in 4.6% (18/392). The most frequent ADRs were infection and infestation (3.3%), with herpes zoster being the most common. ADRs were significantly higher in patients with concomitant corticosteroid use (odds ratio [OR], 3.45; 95% confidence interval [CI], 1.40-9.68). No significant difference in ADR incidence was observed between patients aged ≥65 and <65 years (OR, 1.23; 95% CI, 0.35-3.47). Six-week effectiveness of GLM was confirmed by a decrease in the partial Mayo score (-2.3; 95% CI, -2.6 to -2.1) and C-reactive protein levels (-0.64; 95% CI, -0.92 to -0.36), including in the biologics-experienced population.

Conclusions: The safety and effectiveness of GLM at week 6 in a real-world setting were demonstrated in patients with UC in Japan. ADR patterns were consistent with previous reports with no new safety signals. Concomitant corticosteroid use may be associated with increased ADR incidence. The final results of the ongoing PMS are necessary for further evaluation.
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http://dx.doi.org/10.5217/ir.2021.00032DOI Listing
August 2021

The effects of amino acid/protein supplementation in patients undergoing hemodialysis: A systematic review and meta-analysis of randomized controlled trials.

Clin Nutr ESPEN 2021 Aug 7;44:114-121. Epub 2021 May 7.

Department of Physical Therapy, School of Rehabilitation, Hyogo University of Health Sciences, Kobe, Japan.

Background & Aims: We evaluated the efficacy of the intervention consisting of amino acid/protein supplementation on muscle mass, muscle strength and physical function in patients on hemodialysis.

Methods: This systematic review and meta-analysis identified potential studies through a systematic search of 4 electronic databases and references from eligible studies from database inception to August 2020. We included only randomized controlled trials reporting the efficacy of amino acid/protein supplementation on muscle mass, muscle strength and physical function in patients on hemodialysis.

Results: Of 6529 unique citation records, 4 studies including 243 participants were selected for inclusion in the meta-analysis. Although there were no significant differences in muscle mass and muscle strength between the intervention and control groups, amino acid/protein supplementation was shown to significantly improve physical function (shuttle walk, MD 32.7, 95% CI 21.7 to 43.7, P < 0.001; gait speed, MD 0.07, 95% CI 0.01 to 0.13, P = 0.02; timed up and go, MD -0.42, 95% CI -0.68 to -0.15, P = 0.002) in patients on hemodialysis.

Conclusions: We confirmed the positive effect of amino acid/protein supplementation on physical function in people undergoing hemodialysis. However, there is still insufficient evidence, and more rigorously designed randomized controlled trials with high quality are needed.
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http://dx.doi.org/10.1016/j.clnesp.2021.04.027DOI Listing
August 2021
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