960 results on '"Kyo, S"'
Search Results
152. A 10 GIPS SIMD processor for PC-based real time vision applications -architecture, algorithm implementation and language support
- Author
-
Fujita, Y., primary, Kyo, S., additional, Yamashita, N., additional, and Okazaki, S., additional
- Full Text
- View/download PDF
153. An Integrated Memory Array Processor Architecture for Embedded Image Recognition Systems
- Author
-
Kyo, S., primary, Okazaki, S., additional, and Arai, T., additional
- Full Text
- View/download PDF
154. A robust vehicle detecting and tracking system for wet weather conditions using the IMAP-VISION image processing board
- Author
-
Kyo, S., primary, Koga, T., additional, Sakurai, K., additional, and Okazaki, S., additional
- Full Text
- View/download PDF
155. A 51.2 GOPS scalable video recognition processor for intelligent cruise control based on a linear array of 128 4-way VLIW processing elements
- Author
-
Kyo, S., primary, Koga, T., additional, Okazaki, S., additional, Uchida, R., additional, Yoshimoto, S., additional, and Kuroda, I., additional
- Full Text
- View/download PDF
156. A programmable parallel processor LSI for video-based driver assistance systems
- Author
-
Kyo, S., primary, Koga, T., additional, Okazaki, S., additional, and Kuroda, I., additional
- Full Text
- View/download PDF
157. Utility of 10 MHz Ultrasound Catheters in the Intraaortic Assessment of Coronary Artery Ostial Stenoses
- Author
-
Wong, P., Hung, J.-S., Miyamoto, N., Wu, C.-J., Fu, M., Kyo, S., and Omoto, R.
- Published
- 1996
- Full Text
- View/download PDF
158. Conservative management and vaginal delivery following ruptured renal angiomyolipoma.
- Author
-
Tanaka, M, Kyo, S, Inoue, M, and Kojima, T
- Published
- 2001
- Full Text
- View/download PDF
159. A 51.2 GOPS scalable video recognition processor for intelligent cruise control based on a linear array of 128 4-way VLIW processing elements.
- Author
-
Kyo, S., Koga, T., Okazaki, S., Uchida, R., Yoshimoto, S., and Kuroda, I.
- Published
- 2003
- Full Text
- View/download PDF
160. A programmable parallel processor LSI for video-based driver assistance systems.
- Author
-
Kyo, S., Koga, T., Okazaki, S., and Kuroda, I.
- Published
- 2003
- Full Text
- View/download PDF
161. Bone marrow-derived cells from male donors can compose endometrial glands in female transplant recipients.
- Author
-
Ikoma T, Kyo S, Maida Y, Ozaki S, Takakura M, Nakao S, and Inoue M
- Abstract
OBJECTIVE: For continuous regeneration of human endometrium in menstrual cycles, endometrial stem cells are assumed to supply differentiating endometrial glandular cells. To elucidate the origin of endometrial stem cells, we examined the presence of donor-derived cells in endometria from patients who received bone marrow transplantation from male donors. STUDY DESIGN: Endometrial specimens biopsied after hormone replacement therapy were obtained and examined using fluorescent in situ hybridization analysis targeting X or Y chromosomes. RESULTS: All recipients had donor-derived Y chromosome-positive endometrial cells, accounting for 0.6-8.4% of glandular epithelial cells and 8.2-9.8% of stromal cells. Most of the endometrial glands were chimeric, consisting of both donor-derived and recipient cells. CONCLUSION: Donor-derived cells are capable of composing endometrium in recipients, even those of the opposite sex. These results suggest unexpected plasticity of bone marrow stem cells as well as a potential origin of endometrial stem cells. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
162. Value of live 3D transoesophageal echocardiography in the diagnosis of mitral valve lesions.
- Author
-
Uno K, Takenaka K, Ebihara A, Nawata K, Hayashi N, Nagasaki M, Sonoda M, Takayuki O, Ono M, Kyo S, Nagai R, and Takamoto S
- Published
- 2009
- Full Text
- View/download PDF
163. Ventricular-vascular stiffening in patients with repaired coarctation of aorta: integrated pathophysiology of hypertension.
- Author
-
Senzaki H, Iwamoto Y, Ishido H, Masutani S, Taketazu M, Kobayashi T, Katogi T, and Kyo S
- Published
- 2008
164. 13.6 Aortic arch reconstruction using cerebral protection with selective cold blood cerebral perfusion by gravity
- Author
-
Yokote, Y., Ueda, K., Asano, H., Tanabe, H., Kyo, S., and Omoto, R.
- Published
- 1997
- Full Text
- View/download PDF
165. Prognostic role and implications of mutation status of tumor suppressor gene ARID1A in cancer: A systematic review and meta-analysis
- Author
-
Aldo Scarpa, Jae Hoon Kim, George M. Yousef, Hai Bo Yan, Duck Woo Kim, Andreas Scorilas, Angela Chou, Giuseppe Sergi, Anthony J. Gill, Da Pang, Marco Solmi, Alcides Chaux, Yoshihito Yokoyama, Gregg Nelson, Nicola Veronese, Martin Köbel, Christoph U. Correll, David F. Schaeffer, George J. Netto, Satoru Kyo, Feng Liu, Claudio Luchini, Laura D. Wood, Soo Young Lee, Zsuzsanna Lichner, Hanbyoul Cho, Kentaro Nakayama, Paola Capelli, Sheila F. Faraj, Steve E. Kalloger, Xianyu Zhang, Enzo Manzato, Luchini, C., Veronese, N., Solmi, M., Cho, H., Kim, J.-H., Chou, A., Gill, A.J., Faraj, S.F., Chaux, A., Netto, G.J., Nakayama, K., Kyo, S., Lee, S.Y., Kim, D.-W., Yousef, G.M., Scorilas, A., Nelson, G.S., Köbel, M., Kalloger, S.E., Schaeffer, D.F., Yan, H.-B., Liu, F., Yokoyama, Y., Zhang, X., Pang, D., Lichner, Z., Sergi, G., Manzato, E., Capelli, P., Wood, L.D., Scarpa, A., and Correll, C.U.
- Subjects
Oncology ,Male ,medicine.medical_specialty ,Bioinformatics ,ARID1A, SWI/SNF, chromatin remodeling, targeted therapy, tumor suppressor gene ,chromatin remodeling ,Cohort Studies ,ARID1A ,Chromatin remodeling ,SWI/SNF ,Targeted therapy ,Tumor suppressor gene ,Internal medicine ,Neoplasms ,Medicine ,Humans ,targeted therapy ,tumor suppressor gene ,Genes, Tumor Suppressor ,Prospective cohort study ,business.industry ,Confounding ,Hazard ratio ,Cancer ,Nuclear Proteins ,Middle Aged ,medicine.disease ,Prognosis ,Confidence interval ,DNA-Binding Proteins ,Relative risk ,Meta-analysis ,Mutation ,Female ,business ,Cohort study ,Research Paper ,Transcription Factors - Abstract
Loss of the tumor suppressor gene AT-rich interactive domain-containing protein 1A (ARID1A) has been demonstrated in several cancers, but its prognostic role is unknown. We aimed to investigate the risk associated with loss of ARID1A (ARID1A-) for all-cause mortality, cancer-specific mortality and recurrence of disease in subjects with cancer. PubMed and SCOPUS search from database inception until 01/31/2015 without language restriction was conducted, contacting authors for unpublished data. Eligible were prospective studies reporting data on prognostic parameters in subjects with cancer, comparing participants with presence of ARID1A (ARID1A+) vs. ARID1A-, assessed either via immunohistochemistry (loss of expression) or with genetic testing (presence of mutation). Data were summarized using risk ratios (RR) for number of deaths/recurrences and hazard ratios (HR) for time-dependent risk related to ARID1A- adjusted for potential confounders. Of 136 hits, 25 studies with 5,651 participants (28 cohorts; ARID1A-: n = 1,701; ARID1A+: n = 3,950), with a mean follow-up period of 4.7 ± 1.8 years, were meta-analyzed. Compared to ARID1A+, ARID1A- significantly increased cancer-specific mortality (studies = 3; RR = 1.55, 95% confidence interval (CI) = 1.19-2.00, I(2) = 31%). Using HRs adjusted for potential confounders, ARID1A- was associated with a greater risk of cancer-specific mortality (studies = 2; HR = 2.55, 95%CI = 1.19-5.45, I(2) = 19%) and cancer recurrence (studies = 10; HR = 1.93, 95%CI = 1.22-3.05, I(2) = 76%). On the basis of these results, we have demonstrated that loss of ARID1A shortened time to cancer-specific mortality, and to recurrence of cancer when adjusting for potential confounders. For its role, this gene should be considered as an important potential target for personalized medicine in cancer treatment.
- Published
- 2015
166. Rethinking appropriate blanking period after atrial fibrillation ablation.
- Author
-
Onishi N, Suenaga A, Yoshida A, Kobayashi T, Kyo S, Oi M, Higashitani N, Nakazeki F, Oyamada N, Jinnai T, and Kaitani K
- Subjects
- Humans, Male, Female, Retrospective Studies, Middle Aged, Time Factors, Risk Factors, Aged, Atrial Fibrillation surgery, Catheter Ablation methods, Recurrence
- Abstract
Background: Early recurrence (ER) within a 90-day blanking period (BP) in catheter ablation (CA) for atrial fibrillation (AF) is a risk factor for late recurrence (LR) after 90 days postoperatively. However, few reports have examined them in the second CA and compared them to the first CA. Moreover, in recent years, there have been reports suggesting that BP should be reduced from 90 to 30 days. Therefore, the association between ER and LR in the first and the second CA was examined, and the validity of a 30-day BP was evaluated., Methods: A total of 511 consecutive patients undergoing the first CA and 116 of these patients undergoing the second CA for AF at a single institution from November 2016 to December 2020 were analyzed retrospectively., Results: When ER within a 90-day BP was divided into 0-30 days and 31-90 days according to the timing of the last ER episode, the hazard ratios on LR of them relative to no ER were 2.7 {95% confidence interval (CI) 1.7-4.2} and 9.7 (95% CI 6.6-14.3), respectively, for the first CA and 15.3 (95% CI 4.7-50.1) and 44.1 (95% CI 14.0-139.4), respectively, for the second CA., Conclusions: ER was strongly associated with LR, especially in patients with the last episode of ER more than 30 days after CA. This was pronounced in cases after the second CA, when PVI appeared to be completed. With the current improvement in PVI durability, BP may be acceptable for 30 days., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2024
- Full Text
- View/download PDF
167. JCS/JSCVS/JCC/CVIT 2023 guideline focused update on indication and operation of PCPS/ECMO/IMPELLA.
- Author
-
Nishimura T, Hirata Y, Ise T, Iwano H, Izutani H, Kinugawa K, Kitai T, Ohno T, Ohtani T, Okumura T, Ono M, Satomi K, Shiose A, Toda K, Tsukamoto Y, Yamaguchi O, Fujino T, Hashimoto T, Higashi H, Higashino A, Kondo T, Kurobe H, Miyoshi T, Nakamoto K, Nakamura M, Saito T, Saku K, Shimada S, Sonoda H, Unai S, Ushijima T, Watanabe T, Yahagi K, Fukushima N, Inomata T, Kyo S, Minamino T, Minatoya K, Sakata Y, and Sawa Y
- Subjects
- Humans, Cardiology, Extracorporeal Membrane Oxygenation
- Published
- 2024
- Full Text
- View/download PDF
168. Quality of care measurement for patients with ovarian cancer in Japan.
- Author
-
Kakuwa T, Watanabe T, Niino M, Kawata A, Satoh T, Matsumura N, Yokoyama Y, Kawana K, Hirashima Y, Kyo S, Yasuda M, Harano K, Machida H, Tokunaga H, Kaneuchi M, Tabata T, Kobayashi Y, Nagase S, Katabuchi H, Mikami M, Yamamoto Y, Rikitake R, Ichinose Y, and Higashi T
- Subjects
- Humans, Female, Japan, Guideline Adherence statistics & numerical data, Ovarian Neoplasms therapy, Quality Indicators, Health Care, Quality of Health Care standards
- Abstract
Aim: Quality of care is important to reduce disease progression, and improve both survival and quality of life. The Japan Society of Gynecologic Oncology has published treatment guidelines to promote standardized high-quality care for ovarian cancer in Japan. We developed quality indicators based on the guideline recommendations and used them on large datasets of health service use to examine the quality of ovarian cancer care., Methods: A panel of experts developed the indicators using a modified Delphi method. Adherence to each indicator was evaluated using data from a hospital-based cancer registry of patients diagnosed in 2018. All patients receiving first-line treatment at participating facilities were included. The adherence rates were returned to participating hospitals, and reasons for nonadherence were collected. A total of 580 hospitals participated, and the study examined the care received by 6611 patients with ovarian cancer and 1879 with borderline tumors using 11 measurable quality indicators., Results: The adherence rate ranged from 22.6% for "Estrogen replacement within 6 months of operation" to 93.5% for "Bleomycin, etoposide, and cisplatin for germ cell tumor more than Stage II." Of 580 hospitals, 184 submitted the reasons for nonadherence., Conclusions: The quality of ovarian cancer care should be continuously assessed to encourage the use of best practices. These indicators may be a useful tool for this purpose., (© 2024 The Authors. Journal of Obstetrics and Gynaecology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Obstetrics and Gynecology.)
- Published
- 2024
- Full Text
- View/download PDF
169. Evaluation of ARID1A as a Potential Biomarker for Predicting Response to Immune Checkpoint Inhibitors in Patients with Endometrial Cancer.
- Author
-
Yamashita H, Nakayama K, Kanno K, Ishibashi T, Ishikawa M, Iida K, Razia S, Kiyono T, and Kyo S
- Abstract
Background: AT-rich interaction domain 1A (ARID1A) has been proposed as a new biomarker for predicting response to immune checkpoint inhibitors (ICIs). The predictive value of ARID1A for predicting ICI effectiveness has not been reported for endometrial cancer. Therefore, we investigated whether ARID1A negativity predicts ICI effectiveness for endometrial cancer treatment., Methods: We evaluated ARID1A expression, tumor-infiltrating lymphocytes (CD8+), and immune checkpoint molecules (PD-L1/PD-1) by immunostaining endometrial samples from patients with endometrial cancer. Samples in which any of the four mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2) were determined to be negative via immunostaining were excluded. In the ARID1A-negative group, microsatellite instability (MSI) status was confirmed via MSI analysis., Results: Of the 102 samples investigated, 25 (24.5%) were ARID1A-negative. CD8 and PD-1 expression did not differ significantly between the ARID1A-negative group and the ARID1A-positive group; however, the ARID1A-negative group showed significantly lower PD-L1 expression. Only three samples (14.2%) in the ARID1A-negative group showed high MSI. Sanger sequencing detected three cases of pathological mutation in the MSH2-binding regions. We also established an ARID1A-knockout human ovarian endometriotic epithelial cell line (HMOsisEC7 ARID1A KO), which remained microsatellite-stable after passage., Conclusion: ARID1A negativity is not suitable as a biomarker for ICI effectiveness in treating endometrial cancer.
- Published
- 2024
- Full Text
- View/download PDF
170. Editor's Note: Activation of NF-κB Is a Novel Target of KRAS-induced Endometrial Carcinogenesis.
- Author
-
Mizumoto Y, Kyo S, Kiyono T, Takakura M, Nakamura M, Maida Y, Mori N, Bono Y, Sakurai H, and Inoue M
- Published
- 2024
- Full Text
- View/download PDF
171. Association between KRAS and PIK3CA Mutations and Progesterone Resistance in Endometriotic Epithelial Cell Line.
- Author
-
Kanno K, Nakayama K, Razia S, Islam SH, Farzana ZU, Sonia SB, Yamashita H, Ishikawa M, Ishibashi T, Imamura K, Kiyono T, and Kyo S
- Abstract
Although endometriosis is a benign disease, it is associated with cancer-related gene mutations, such as KRAS or PIK3CA . Endometriosis is associated with elevated levels of inflammatory factors that cause severe pain. In a previous study, we demonstrated that KRAS or PIK3CA mutations are associated with the activation of cell proliferation, migration, and invasion in a patient-derived immortalized endometriotic cell line, HMOsisEC10. In this study, we investigated the effects of these mutations on progesterone resistance. Since the HMOsisEC10 had suppressed progesterone receptor (PR) expression, we transduced PR-B to HMOsisEc10 cell lines including KRAS mutant and PIK3CA mutant cell lines. We conducted a migration assay, invasion assay, and MTT assay using dienogest and medroxyprogestrone acetate. All cell lines showed progesterone sensitivity with or without mutations. Regarding inflammatory factors, real-time quantitative RT-PCR revealed that the KRAS mutation cell line exhibited no suppression of Cox-2 and mPGES-1 on progesterone treatment, whereas IL-6, MCP-1, VEGF, and CYP19A1 were significantly suppressed by progesterone in both mutated cell lines. Our results suggest that KRAS mutation and PIK3CA mutation in endometriotic cells may not be associated with progesterone resistance in terms of aggressiveness. However, KRAS mutations may be associated with progesterone resistance in the context of pain.
- Published
- 2024
- Full Text
- View/download PDF
172. Impact of current and previous sperm findings on outcomes of intrauterine insemination.
- Author
-
Taniguchi M, Kanasaki H, Oride A, Okada H, Imamura K, and Kyo S
- Abstract
Purpose: To examine the association between semen characteristics and outcomes of intrauterine insemination (IUI)., Methods: This retrospective analysis examined 1380 IUI procedures involving 421 couples. The association of clinical pregnancy with pre- and post-wash sperm characteristics was assessed., Results: Pre- and post-wash sperm characteristics did not differ between IUI cycles that resulted in pregnancy and those that did not. When the motility of pre-wash sperm was below the normal range (<42%) established by the World Health Organization (WHO), the pregnancy rate was significantly lower. In the IUI cycles when post-wash sperm motility was below the WHO standard, pregnancy was not achieved. The frequency of improvement in post-wash sperm motility in repeated IUI cycles appeared to correlate with the success of future IUI cycles. At the fourth IUI cycle, pregnancy was not achieved unless the post-wash sperm motility was normal in at least two of three attempts. When post-wash sperm concentration was below the normal range, the woman's age did not affect the IUI outcomes., Conclusions: Sperm motility above the lower limit of the WHO criteria in post-wash semen samples is an important factor in IUI outcomes., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.)
- Published
- 2024
- Full Text
- View/download PDF
173. Changes in pituitary gonadotropin subunits and hypothalamic Kiss-1 gene expression by administration of sex steroids in ovary-intact female rats.
- Author
-
Yacca SS, Kanasaki H, Tumurbaatar T, Cairang Z, Oride A, Okada H, and Kyo S
- Subjects
- Rats, Female, Animals, Hypothalamus metabolism, Gonadotropins, Pituitary genetics, Gonadotropins, Pituitary metabolism, Gonadotropin-Releasing Hormone genetics, Gonadotropin-Releasing Hormone metabolism, Estradiol pharmacology, RNA, Messenger metabolism, Dihydrotestosterone pharmacology, Gene Expression, Ovary, Kisspeptins genetics, Kisspeptins metabolism
- Abstract
Objective: We examined how the sex steroids influence the synthesis of gonadotropins., Materials and Methods: The effects of sex steroids estradiol (E2), progesterone (P4), and dihydrotestosterone (DHT) in pituitary gonadotroph cell model (LβT2 cells) in vitro and ovary-intact rats in vivo were examined. The effects of sex steroids on Kiss1 gene expression in the hypothalamus were also examined in ovary-intact rats., Results: In LβT2 cells, E2 increased common glycoprotein alpha (Cga) and luteinizing hormone beta (Lhb) subunit promoter activity as well as their mRNA expression. Although gonadotropin subunit promoter activity was not modulated by P4, Cga and Lhb mRNA expression was increased by P4. DHT inhibited Cga and Lhb mRNA expression with a concomitant decrease in their promoter activity. During the 2-week administration of exogenous E2 to ovary-intact rats, the estrous cycle determined by vaginal smears was disrupted. P4 or DHT administration completely eliminated the estrous cycle. Protein expression of all three gonadotropin subunits within the pituitary gland was inhibited by E2 or P4 treatment in vivo; however, DHT reduced Cga expression but did not modulate Lhb or follicle-stimulating hormone beta subunit expression. E2 administration significantly repressed Kiss1 mRNA expression in a posterior hypothalamic region that included the arcuate nucleus. P4 and DHT did not modulate Kiss1 mRNA expression in this region. In contrast, P4 administration significantly inhibited Kiss1 mRNA expression in the anterior region of the hypothalamus that included the anteroventral periventricular nucleus. The expression of gonadotropin-releasing hormone (Gnrh) mRNA in the anterior hypothalamic region, where the preoptic area is located, appeared to be decreased by treatment with E2 and P4., Conclusion: Our findings suggest that sex steroids have different effects in the hypothalamus and pituitary gland., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2024
- Full Text
- View/download PDF
174. Current concept of low-grade serous ovarian carcinoma.
- Author
-
Nakayama K, Razia S, Ishibashi T, and Kyo S
- Abstract
Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-23-1161/coif). The authors have no conflicts of interest to declare.
- Published
- 2024
- Full Text
- View/download PDF
175. CORRIGENDUM: JCS/JSCVS/JCC/CVIT 2023 Guideline Focused Update on Indication and Operation of PCPS/ECMO/IMPELLA.
- Author
-
Nishimura T, Hirata Y, Ise T, Iwano H, Izutani H, Kinugawa K, Kitai T, Ohno T, Ohtani T, Okumura T, Ono M, Satomi K, Shiose A, Toda K, Tsukamoto Y, Yamaguchi O, Fujino T, Hashimoto T, Higashi H, Higashino A, Kondo T, Kurobe H, Miyoshi T, Nakamoto K, Nakamura M, Saito T, Saku K, Shimada S, Sonoda H, Unai S, Ushijima T, Watanabe T, Yahagi K, Fukushima N, Inomata T, Kyo S, Minamino T, Minatoya K, and Sakata Y
- Subjects
- Humans, Heart-Assist Devices, Practice Guidelines as Topic standards, Heart Failure therapy, Heart Failure surgery, Extracorporeal Membrane Oxygenation
- Published
- 2024
- Full Text
- View/download PDF
176. Severe Left Ventricular Failure Unmanageable by Impella 5.0.
- Author
-
Mano A, Murata T, Inui A, Kawata M, and Kyo S
- Abstract
Mechanical circulatory support can be beneficial for patients with cardiogenic shock. Of these, the Impella has recently become the first-line device due to its feasibility, minimal invasiveness, and efficacy. We had a 58-year-old male with acute myocardial infarction followed by cardiogenic shock. We initially placed the patient on intra-aortic balloon pumping, which was switched to Impella 2.5 and could stabilize him. Unfortunately, the Impella 2.5 device suddenly stopped on the fifth day, thus, we tried to manage him by inotropes. However, his condition gradually deteriorated, so we applied Impella 5.0. Although his systemic circulation could be maintained, severe pulmonary hypertension persisted on Impella 5.0. He developed flash pulmonary edema, thus, we emergently added venoarterial extracorporeal membrane oxygenation on Impella 5.0 (ECPELLA). Then, we removed Impella 5.0 and changed peripheral venoarterial extracorporeal membrane oxygenation to central venoarterial extracorporeal membrane oxygenation. In this central venoarterial extracorporeal membrane oxygenation, we inserted the cannulas in the pulmonary artery and the left ventricle in addition to the usual cannulas in the ascending aorta and the right atrium. We aimed to control pulmonary arterial blood flow for lung protection as well as left ventricular unloading by this modification. However, his cardiac function showed no signs of recovery, and his lung condition showed further exacerbation. He was complicated by fungal sepsis and finally died of multi-organ failure. Although the Impella is an option, it is crucial to evaluate patients' condition carefully and to escalate the device, if needed, without delay., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Mano et al.)
- Published
- 2023
- Full Text
- View/download PDF
177. Dexmedetomidine for dyspnoea.
- Author
-
Mano A, Murata T, Date K, Kawata M, Sato M, Yamashita N, Iino K, Kyo S, and Saito E
- Subjects
- Humans, Hypnotics and Sedatives therapeutic use, Pain, Intensive Care Units, Dyspnea drug therapy, Dyspnea etiology, Dexmedetomidine therapeutic use
- Abstract
Dexmedetomidine is a selective α
2 -adrenoreceptor agonist with a broad range of effects, including easily controllable sedation, analgesia and anxiolysis. Because of these favorable features, it has replaced traditional sedatives, such as benzodiazepines, and is becoming the first-line sedative for the patients in intensive care units. Terminally ill patients often need sedatives for symptom management, especially for dyspnoea. However, the use of dexmedetomidine in a palliative care setting has rarely been recognised to date. We experienced a patient nearing the end of life due to uncontrollable pulmonary haemorrhage on ventilator, whose dyspnoea was successfully managed by dexmedetomidine in addition to continuous intravenous infusion of oxycodone., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)- Published
- 2023
- Full Text
- View/download PDF
178. Integrative analysis reveals early epigenetic alterations in high-grade serous ovarian carcinomas.
- Author
-
Machino H, Dozen A, Konaka M, Komatsu M, Nakamura K, Ikawa N, Shozu K, Asada K, Kaneko S, Yoshida H, Kato T, Nakayama K, Saloura V, Kyo S, and Hamamoto R
- Subjects
- Female, Humans, Proteasome Endopeptidase Complex metabolism, Carcinogenesis genetics, Transcription Factors metabolism, Epigenesis, Genetic, Mitogen-Activated Protein Kinase Kinases metabolism, Ovarian Neoplasms metabolism, Cystadenocarcinoma, Serous genetics, Cystadenocarcinoma, Serous metabolism, Cystadenocarcinoma, Serous pathology
- Abstract
High-grade serous ovarian carcinoma (HGSOC) is the most lethal gynecological malignancy. To date, the profiles of gene mutations and copy number alterations in HGSOC have been well characterized. However, the patterns of epigenetic alterations and transcription factor dysregulation in HGSOC have not yet been fully elucidated. In this study, we performed integrative omics analyses of a series of stepwise HGSOC model cells originating from human fallopian tube secretory epithelial cells (HFTSECs) to investigate early epigenetic alterations in HGSOC tumorigenesis. Assay for transposase-accessible chromatin using sequencing (ATAC-seq), chromatin immunoprecipitation sequencing (ChIP-seq), and RNA sequencing (RNA-seq) methods were used to analyze HGSOC samples. Additionally, protein expression changes in target genes were confirmed using normal HFTSECs, serous tubal intraepithelial carcinomas (STICs), and HGSOC tissues. Transcription factor motif analysis revealed that the DNA-binding activity of the AP-1 complex and GATA family proteins was dysregulated during early tumorigenesis. The protein expression levels of JUN and FOSL2 were increased, and those of GATA6 and DAB2 were decreased in STIC lesions, which were associated with epithelial-mesenchymal transition (EMT) and proteasome downregulation. The genomic region around the FRA16D site, containing a cadherin cluster region, was epigenetically suppressed by oncogenic signaling. Proteasome inhibition caused the upregulation of chemokine genes, which may facilitate immune evasion during HGSOC tumorigenesis. Importantly, MEK inhibitor treatment reversed these oncogenic alterations, indicating its clinical effectiveness in a subgroup of patients with HGSOC. This result suggests that MEK inhibitor therapy may be an effective treatment option for chemotherapy-resistant HGSOC., (© 2023. The Author(s).)
- Published
- 2023
- Full Text
- View/download PDF
179. Fusobacterium infection facilitates the development of endometriosis through the phenotypic transition of endometrial fibroblasts.
- Author
-
Muraoka A, Suzuki M, Hamaguchi T, Watanabe S, Iijima K, Murofushi Y, Shinjo K, Osuka S, Hariyama Y, Ito M, Ohno K, Kiyono T, Kyo S, Iwase A, Kikkawa F, Kajiyama H, and Kondo Y
- Subjects
- Female, Animals, Mice, Humans, Fibroblasts, Myofibroblasts, Disease Models, Animal, Endometrium, Endometriosis, Fusobacterium Infections
- Abstract
Retrograde menstruation is a widely accepted cause of endometriosis. However, not all women who experience retrograde menstruation develop endometriosis, and the mechanisms underlying these observations are not yet understood. Here, we demonstrated a pathogenic role of Fusobacterium in the formation of ovarian endometriosis. In a cohort of women, 64% of patients with endometriosis but <10% of controls were found to have Fusobacterium infiltration in the endometrium. Immunohistochemical and biochemical analyses revealed that activated transforming growth factor-β (TGF-β) signaling resulting from Fusobacterium infection of endometrial cells led to the transition from quiescent fibroblasts to transgelin (TAGLN)-positive myofibroblasts, which gained the ability to proliferate, adhere, and migrate in vitro. Fusobacterium inoculation in a syngeneic mouse model of endometriosis resulted in a marked increase in TAGLN-positive myofibroblasts and increased number and weight of endometriotic lesions. Furthermore, antibiotic treatment largely prevented establishment of endometriosis and reduced the number and weight of established endometriotic lesions in the mouse model. Our data support a mechanism for the pathogenesis of endometriosis via Fusobacterium infection and suggest that eradication of this bacterium could be an approach to treat endometriosis.
- Published
- 2023
- Full Text
- View/download PDF
180. Kisspeptin induces Kiss-1 and GnRH gene expression in mHypoA-55 hypothalamic cell models: Involvement of the ERK and PKA signaling pathways.
- Author
-
Tumurbaatar T, Kanasaki H, Yacca SS, Cairang Z, Tumurgan Z, Oride A, Okada H, and Kyo S
- Subjects
- Animals, Mice, Cell Line, Extracellular Signal-Regulated MAP Kinases metabolism, Gene Expression, Hypothalamus metabolism, MAP Kinase Kinase Kinases genetics, MAP Kinase Kinase Kinases metabolism, Signal Transduction, Gonadotropin-Releasing Hormone genetics, Gonadotropin-Releasing Hormone pharmacology, Gonadotropin-Releasing Hormone metabolism, Kisspeptins genetics, Kisspeptins metabolism
- Abstract
mHypoA-55 cells are kisspeptin-expressing neuronal cells originating from the arcuate nucleus of the mouse hypothalamus. These cells are called KNDy neurons because they co-express kisspeptin, neurokinin B, and dynorphin A. In addition, they express gonadotropin-releasing hormone (GnRH). Here, we found that kisspeptin 10 (KP10) increased Kiss-1 (encoding kisspeptin) and GnRH gene expression in kisspeptin receptor (Kiss-1R)-overexpressing mHypoA-55 cells. KP10 greatly increased serum response element (SRE) promoter activity, which is a target of extracellular signal-regulated kinase (ERK) (20.0 ± 2.54-fold). KP10 also increased cAMP-response element (CRE) promoter activity in these cells (2.32 ± 0.36-fold). KP10-increased SRE promoter activity was significantly prevented in the presence of PD098095, a MEK kinase (MEKK) inhibitor, and KP10-induced CRE promoter activity was also inhibited by PD098059. Similarly, H89, a protein kinase A (PKA) inhibitor, significantly inhibited the KP10 induction of SRE and CRE promoters. KP10-induced Kiss-1 and GnRH gene expressions were inhibited in the presence of PD098059. Likewise, H89 significantly inhibited the KP10-induced increase in Kiss-1 and GnRH. Transfection of mHypoA-55 cells with constitutively active MEKK (pFC-MEKK) increased SRE and CRE promoter activities by 9.75 ± 1.77- and 1.36 ± 0.12-fold, respectively. Induction of constitutively active PKA (pFC-PKA) also increased SRE and CRE promoter activities by 2.41 ± 0.42- and 40.71 ± 7.77-fold, respectively. Furthermore, pFC-MEKK and -PKA transfection of mHypoA-55 cells increased both Kiss-1 and GnRH gene expression. Our current observations suggest that KP10 increases both the ERK and PKA pathways and that both pathways mutually interact in mHypoA-55 hypothalamic cells. Activation of both ERK and PKA signaling might be necessary to induce Kiss-1 and GnRH gene expressions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
181. Frequent PIK3CA mutation in normal endometrial gland drives spheroid formation and may be involved in stem cell propagation.
- Author
-
Sato S, Nakayama K, Kanno K, Sultana R, Ishikawa M, Ishibashi T, Yamashita H, and Kyo S
- Subjects
- Humans, Female, Endometrium, Mutation, Class I Phosphatidylinositol 3-Kinases genetics, Class I Phosphatidylinositol 3-Kinases metabolism, Stem Cells, Proto-Oncogene Proteins p21(ras) genetics, Proto-Oncogene Proteins p21(ras) metabolism, Endometrial Neoplasms genetics, Endometrial Neoplasms metabolism
- Abstract
Recent studies reported the presence of oncogenic mutations in normal endometrial glands, but the biological significance remains unclear. The present study investigated the status of KRAS/PIK3CA driver mutations in normal endometrial glands as well as spheroids derived from single glands. The normal endometria of surgically removed uteri (n = 3) were divided into nine regions, and 40 endometrial single glands were isolated from each region. The DNAs of 10 glands in each region were extracted and subjected to Sanger sequencing for KRAS or PIK3CA driver mutations, while the remaining 30 glands were conferred to a long-term spheroid culture, followed by Sanger sequencing. Immunohistochemical analyses of stem cell (Axin2, ALDH1A1, SOX9) markers were undertaken for spheroids. Sanger sequencing successfully detected oncogenic mutations of KRAS or PIK3CA in a single gland. Twenty-five of the 270 glands (9.3%) had mutations in either KRAS or PIK3CA, and the mutation frequency in each endometrial region varied from 0% to 50%. The droplet digital PCR showed high mutation allele frequency (MAF) of PIK3CA mutation, suggestive of clonal expansion of mutated cells within a gland. Over 60% of the collected spheroids had PIK3CA mutations, but no KRAS mutations were detected. Immunohistochemically, spheroids were mainly composed of cells with stem cell marker expressions. High MAF of PIK3CA mutation in a single gland as well as frequent PIK3CA mutation in stem cell-rich spheroids that originated from a single gland suggest the role of PIK3CA mutation in stem cell propagation. This information could improve our understanding of endometrial physiology as well as stem cell-oriented endometrial regeneration and carcinogenesis., (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
- Published
- 2023
- Full Text
- View/download PDF
182. Fulminant myocarditis with complete atrioventricular block after mRNA COVID-19 vaccination: A case report.
- Author
-
Onishi N, Konishi Y, Kaneko T, Maekawa N, Suenaga A, Nomura S, Kobayashi T, Kyo S, Okabayashi M, Higami H, Oi M, Higashitani N, Saijo S, Nakazeki F, Oyamada N, Jinnai T, Okuno T, Shirase T, and Kaitani K
- Abstract
A 71-year-old man was transferred urgently to our hospital after collapsing near his home post the first shot of the BNT162b2 coronavirus disease 2019 vaccine (Pfizer-BioNTech, Comirnaty®). Immediately after arrival at our hospital, cardiac arrest due to complete atrioventricular block with no ventricular escaped beats was observed on electrocardiogram. Echocardiography showed preserved left ventricular ejection fraction, however, diffuse severe hypokinesia was revealed after 3 weeks, and he died 3 months after admission because of worsening heart failure. An autopsy examination revealed eosinophilic myocarditis or hypersensitivity myocarditis with extensive fibrosis and widespread myocardial dropout throughout the heart., Learning Objective: 1. Severe myocarditis occurs extremely rarely after mRNA coronavirus disease 2019 (COVID-19) vaccination. 2. Myocarditis after mRNA COVID-19 vaccination might cause complete atrioventricular block, followed by a course of decreased left ventricular ejection fraction. 3. Histologically, severe myocarditis after mRNA COVID-19 vaccination seems to present as fulminant necrotizing eosinophilic myocarditis or hypersensitivity myocarditis., Competing Interests: None., (© 2023 Japanese College of Cardiology. Published by Elsevier Ltd.)
- Published
- 2023
- Full Text
- View/download PDF
183. Androgen promotes squamous differentiation of atypical cells in cervical intraepithelial neoplasia via an ELF3-dependent pathway.
- Author
-
Matsumoto T, Suzuki T, Nakamura M, Yamamoto M, Iizuka T, Ono M, Kagami K, Kasama H, Kanda T, Sakai Y, Iwadare J, Matsuoka A, Kayahashi K, Wakae K, Muramatsu M, Kyo S, Yamamoto Y, Mizumoto Y, Daikoku T, and Fujiwara H
- Subjects
- Female, Humans, Androgens pharmacology, Cell Differentiation, DNA-Binding Proteins, Forkhead Transcription Factors, Proto-Oncogene Proteins c-ets, Transcription Factors, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell metabolism, Papillomavirus Infections complications, Uterine Cervical Dysplasia, Uterine Cervical Neoplasms drug therapy, Uterine Cervical Neoplasms genetics, Uterine Cervical Neoplasms metabolism
- Abstract
Background: Since the human papillomavirus vaccines do not eliminate preexisting infections, nonsurgical alternative approaches to cervical intraepithelial neoplasia (CIN) have been required. We previously reported that FOXP4 (forkhead box transcription factor P4) promoted proliferation and inhibited squamous differentiation of CIN1-derived W12 cells. Since it was reported that FOXP expressions were regulated by the androgen/androgen receptor (AR) complex and AR was expressed on the CIN lesions, in this study we examined the effects of androgen on CIN progression., Methods: Since AR expression was negative in W12 cells and HaCaT cells, a human male skin-derived keratinocyte cell line, we transfected AR to these cell lines and investigated the effects of dihydrotestosterone (DHT) on their proliferation and squamous differentiation. We also examined the immunohistochemical expression of AR in CIN lesions., Results: DHT reduced the intranuclear expression of FOXP4, attenuating cell proliferation and promoting squamous differentiation in AR-transfected W12 cells. Si-RNA treatments showed that DHT induced the expression of squamous differentiation-related genes in AR-transfected W12 cells via an ELF3-dependent pathway. DHT also reduced FOXP4 expression in AR-transfected HaCaT cells. An immunohistochemical study showed that AR was expressed in the basal to parabasal layers of the normal cervical epithelium. In CIN1 and 2 lesions, AR was detected in atypical squamous cells, whereas AR expression had almost disappeared in the CIN3 lesion and was not detected in SCC, suggesting that androgens do not act to promote squamous differentiation in the late stages of CIN., Conclusion: Androgen is a novel factor that regulates squamous differentiation in the early stage of CIN, providing a new strategy for nonsurgical and hormone-induced differentiation therapy against CIN1 and CIN2., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
- Published
- 2023
- Full Text
- View/download PDF
184. Promising Therapeutic Impact of Immune Checkpoint Inhibitors in Type II Endometrial Cancer Patients with Deficient Mismatch Repair Status.
- Author
-
Sawada K, Nakayama K, Razia S, Yamashita H, Ishibashi T, Ishikawa M, Kanno K, Sato S, Nakayama S, Otsuki Y, and Kyo S
- Abstract
Type II endometrial cancer (EC) is responsible for most endometrial cancer-related deaths due to its aggressive nature, late-stage detection, and high tolerance to standard therapies. Thus, novel treatment strategies for type II EC are imperative. For patients with mismatch repair-deficient (dMMR) tumors, immunotherapy with immune checkpoint inhibitors represents a promising therapeutic strategy. However, the prevalence of dMMR tumors in type II EC patients remains unclear. In this study, using immunohistochemistry, we evaluated the expression of mismatch repair (MMR) proteins, tumor-infiltrating lymphocytes (CD8+), and immune checkpoint molecules (PD-L1) in 60 patients with type II EC (16, 5, 17, and 22 were endometrioid G3, serous, de-differentiated, and carcinosarcoma cases, respectively) to investigate the therapeutic effect of immune checkpoint inhibitors. Approximately 24 cases (40%) had a loss of MMR protein expression. The positivity rate of CD8+ ( p = 0.0072) and PD-L1 ( p = 0.0061) expression was significantly associated with the dMMR group. These results suggest immune checkpoint inhibitors (anti-PD-L1/PD-1 antibodies) could effectively treat type II EC with dMMR. The presence of dMMR might be a biomarker for a positive response to PD-1/PD-L1 immunotherapy in type II EC.
- Published
- 2023
- Full Text
- View/download PDF
185. Histological and Genetic Diversity in Ovarian Mucinous Carcinomas: A Pilot Study.
- Author
-
Razia S, Nakayama K, Yamashita H, Ishibashi T, Ishikawa M, Kanno K, Sato S, and Kyo S
- Subjects
- Female, Humans, Pilot Projects, Carcinoma, Ovarian Epithelial, Mutation, Adenocarcinoma, Mucinous genetics, Adenocarcinoma, Mucinous pathology, Ovarian Neoplasms diagnosis
- Abstract
Tumor heterogeneity remains an ongoing challenge in the field of cancer therapy. Intratumor heterogeneity significantly complicates the diagnosis of cancer and presents challenging clinical problems due to resistance to drug therapy. This study aimed to elucidate the genetic changes histologically (mucinous cystadenoma (MCA), mucinous borderline tumor (MBT), and mucinous ovarian carcinoma (MOC)) in a portion of mucinous ovarian tumors within the same sample. Seven tumor samples obtained from different patients were used to evaluate the genetic mutations in each component. Intratumor genetic heterogeneity was observed in all patients; among them, BRAF (V600E) and p53 (T118I, P142S, T150I, and T170M) point mutations were observed in the MBT component, while KRAS (G12D and G13D) and PIK3CA (E545K) mutations were found in the MOC component. The current findings suggest that diverse genetic alterations occur in mucinous tumors, according to tumor histology. Tumor heterogeneity and genetic diversity in mucinous ovarian tumors might be the cause of treatment failure. Knowledge of intertumor heterogeneity may lead to an increased understanding of the tumor response to treatment.
- Published
- 2023
- Full Text
- View/download PDF
186. The Case of an Endometrial Cancer Patient with Breast Cancer Who Has Achieved Long-Term Survival via Letrozole Monotherapy.
- Author
-
Ishikawa M, Nakayama K, Razia S, Yamashita H, Ishibashi T, Haraga H, Kanno K, Ishikawa N, and Kyo S
- Abstract
Herein, we present the successful treatment of a 92-year-old woman who experienced recurrent EC in the vaginal stump and para-aortic lymph nodes. The patient was first treated with paclitaxel and carboplatin for recurrent EC, which was abandoned after two cycles of chemotherapy because of G4 hematologic toxicity. Later, the patient was treated with letrozole for early-stage breast cancer, which was diagnosed simultaneously with EC recurrence. After four months of hormonal therapy, a partial response was observed not only in the lesions in the breast, but also those in the vaginal stump and para-aortic lymph nodes. She had no recurrence of breast cancer or EC, even after six years of treatment with letrozole-based hormonal therapy. Subsequent whole-exome sequencing using the genomic DNA isolated from the surgical specimen in the uterine tumor identified several genetic variants, including actionable mutations, such as CTNNB1 (p.S37F), PIK3R1 (p.M582Is_10), and TP53 c.375 + 5G>T. These data suggest that the efficacy of letrozole is mediated by blocking the mammalian target of the rapamycin pathway. The findings of this study, substantiated via genetic analysis, suggest the possibility of long-term disease-free survival, even in elderly patients with recurrent EC, which was thought to be difficult to cure completely.
- Published
- 2023
- Full Text
- View/download PDF
187. Identifying the Carcinogenic Mechanism of Malignant Struma Ovarii Using Whole-Exome Sequencing and DNA Methylation Analysis.
- Author
-
Yamashita H, Nakayama K, Kanno K, Ishibashi T, Ishikawa M, Sato S, Iida K, Razia S, and Kyo S
- Abstract
Background: Since malignant struma ovarii is a very rare disease, its carcinogenic mechanism has not been elucidated. Here, we sought to identify the genetic lesions that may have led to the carcinogenesis of a rare case of malignant struma ovarii (follicular carcinoma) with peritoneal dissemination., Methods: DNA was extracted from the paraffin-embedded sections of normal uterine tissues and malignant struma ovarii for genetic analysis. Whole-exome sequencing and DNA methylation analysis were then performed., Results: Germline variants of RECQL4 , CNTNAP2 , and PRDM2 , which are tumor-suppressor genes, were detected by whole-exome sequencing. Somatic uniparental disomy (UPD) was also observed in these three genes. Additionally, the methylation of FRMD6-AS2 , SESN3 , CYTL1 , MIR4429 , HIF3A , and ATP1B2 , which are associated with tumor growth suppression, was detected by DNA methylation analysis., Conclusions: Somatic UPD and DNA methylation in tumor suppressor genes may be associated with the pathogenesis of malignant struma ovarii. To our knowledge, this is the first report of whole-exome sequencing and DNA methylation analysis in malignant struma ovarii. Genetic and DNA methylation analysis may help elucidate the mechanism of carcinogenesis in rare diseases and guide treatment decisions.
- Published
- 2023
- Full Text
- View/download PDF
188. CORRIGENDUM: JCS/JACR 2021 Guideline on Rehabilitation in Patients With Cardiovascular Disease.
- Author
-
Makita S, Yasu T, Akashi YJ, Adachi H, Izawa H, Ishihara S, Iso Y, Ohuchi H, Omiya K, Ohya Y, Okita K, Kimura Y, Koike A, Kohzuki M, Koba S, Sata M, Shimada K, Shimokawa T, Shiraishi H, Sumitomo N, Takahashi T, Takura T, Tsutsui H, Nagayama M, Hasegawa E, Fukumoto Y, Furukawa Y, Miura SI, Yasuda S, Yamada S, Yamada Y, Yumino D, Yoshida T, Adachi T, Ikegame T, Izawa KP, Ishida T, Ozasa N, Osada N, Obata H, Kakutani N, Kasahara Y, Kato M, Kamiya K, Kinugawa S, Kono Y, Kobayashi Y, Koyama T, Sase K, Sato S, Shibata T, Suzuki N, Tamaki D, Yamaoka-Tojo M, Nakanishi M, Nakane E, Nishizaki M, Higo T, Fujimi K, Honda T, Matsumoto Y, Matsumoto N, Miyawaki I, Murata M, Yagi S, Yanase M, Yamada M, Yokoyama M, Watanabe N, Itoh H, Kimura T, Kyo S, Goto Y, Nohara R, and Hirata KI
- Published
- 2023
- Full Text
- View/download PDF
189. JCS/JACR 2021 Guideline on Rehabilitation in Patients With Cardiovascular Disease.
- Author
-
Makita S, Yasu T, Akashi YJ, Adachi H, Izawa H, Ishihara S, Iso Y, Ohuchi H, Omiya K, Ohya Y, Okita K, Kimura Y, Koike A, Kohzuki M, Koba S, Sata M, Shimada K, Shimokawa T, Shiraishi H, Sumitomo N, Takahashi T, Takura T, Tsutsui H, Nagayama M, Hasegawa E, Fukumoto Y, Furukawa Y, Miura SI, Yasuda S, Yamada S, Yamada Y, Yumino D, Yoshida T, Adachi T, Ikegame T, Izawa KP, Ishida T, Ozasa N, Osada N, Obata H, Kakutani N, Kasahara Y, Kato M, Kamiya K, Kinugawa S, Kono Y, Kobayashi Y, Koyama T, Sase K, Sato S, Shibata T, Suzuki N, Tamaki D, Yamaoka-Tojo M, Nakanishi M, Nakane E, Nishizaki M, Higo T, Fujimi K, Honda T, Matsumoto Y, Matsumoto N, Miyawaki I, Murata M, Yagi S, Yanase M, Yamada M, Yokoyama M, Watanabe N, Itoh H, Kimura T, Kyo S, Goto Y, Nohara R, and Hirata KI
- Subjects
- Humans, Cardiovascular Diseases
- Published
- 2022
- Full Text
- View/download PDF
190. CRTC1 deficiency, specifically in melanocortin-4 receptor-expressing cells, induces hyperphagia, obesity, and insulin resistance.
- Author
-
Matsumura S, Miyakita M, Miyamori H, Kyo S, Ishikawa F, Sasaki T, Jinno T, Tanaka J, Fujita K, Yokokawa T, Goto T, Momma K, Takenaka S, and Inoue K
- Subjects
- Humans, Mice, Animals, Hyperphagia genetics, Hyperphagia metabolism, Obesity genetics, Obesity metabolism, Energy Metabolism, Mice, Knockout, Transcription Factors metabolism, Glucose, Adenosine Monophosphate metabolism, Receptor, Melanocortin, Type 4 genetics, Receptor, Melanocortin, Type 4 metabolism, Insulin Resistance
- Abstract
Melanocortin-4 receptor (MC4R) is a critical regulator of appetite and energy expenditure in rodents and humans. MC4R deficiency causes hyperphagia, reduced energy expenditure, and impaired glucose metabolism. Ligand binding to MC4R activates adenylyl cyclase, resulting in increased levels of intracellular cyclic adenosine monophosphate (cAMP), a secondary messenger that regulates several cellular processes. Cyclic adenosine monophosphate responsive element-binding protein-1-regulated transcription coactivator-1 (CRTC1) is a cytoplasmic coactivator that translocates to the nucleus in response to cAMP and is reportedly involved in obesity. However, the precise mechanism through which CRTC1 regulates energy metabolism remains unknown. Additionally, there are no reports linking CRTC1 and MC4R, although both CRTC1 and MC4R are known to be involved in obesity. Here, we demonstrate that mice lacking CRTC1, specifically in MC4R cells, are sensitive to high-fat diet (HFD)-induced obesity and exhibit hyperphagia and increased body weight gain. Moreover, the loss of CRTC1 in MC4R cells impairs glucose metabolism. MC4R-expressing cell-specific CRTC1 knockout mice did not show changes in body weight gain, food intake, or glucose metabolism when fed a normal-chow diet. Thus, CRTC1 expression in MC4R cells is required for metabolic adaptation to HFD with respect to appetite regulation. Our results revealed an important protective role of CRTC1 in MC4R cells against dietary adaptation., (© 2022 Federation of American Societies for Experimental Biology.)
- Published
- 2022
- Full Text
- View/download PDF
191. Quiescence-inducing neurons-induced hypometabolism ameliorates acute kidney injury in a mouse model mimicking cardiovascular surgery requiring circulatory arrest.
- Author
-
Kyo S, Murata K, Kawatou M, Minatoya K, Sunagawa GA, and Masumoto H
- Abstract
Objectives: Acute kidney injury is a serious complication after cardiovascular surgery requiring circulatory arrest. It is reported that mice can be induced into a hibernation-like hypometabolic state by stimulating a specific neuron located at the hypothalamus (quiescence-inducing neurons-induced hypometabolism [QIH]). Here, we investigated the efficacy of QIH for the amelioration of acute kidney injury in an experimental circulatory arrest using a transgenic mouse model., Methods: We genetically prepared mice in which QIH can be conditionally induced (QIH-ready mice). Mice were divided into 4 groups (n = 6 for each): QIH-ready normothermia (QN), QIH-ready hypothermia (QH), control normothermia (CN), and control hypothermia (CH). After induction of QIH, left thoracotomy and descending aorta crossclamping were conducted. After reperfusion, we collected kidneys and evaluated histologic changes and serum biochemical markers, specifically neutrophil gelatinase-associated lipocalin and cystatin C, indicating early kidney injury., Results: Normothermia showed higher tubular injury scores than those in hypothermia (QN vs QH [ P = .0021] and CN vs CH [ P < .001]). QN exhibited lower neutrophil gelatinase-associated lipocalin and cystatin C levels than those in CN (neutrophil gelatinase-associated lipocalin: CN vs QN: 1.51 ± 0.71 vs 0.82 ± 0.32; P = .0414 and cystatin C: 1.48 ± 0.39 vs 0.71 ± 0.26; P = .0015). There was no significant difference between QN and QH., Conclusions: QIH partly ameliorated acute kidney injury in a mouse ischemia model even in normothermia. QIH might be a promising approach to achieving sufficient kidney protection without hypothermic circulatory arrest in the future., (© 2022 The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
192. Impact of One-Week Administration of Dihydrotestosterone in Rat Anterior Pituitary Gland.
- Author
-
Kanasaki H, Tumurbaatar T, Cairang Z, Tumurgan Z, Oride A, Okada H, and Kyo S
- Abstract
Hyperandrogenism causes dysfunction of the hypothalamic-pituitary-gonadal (HPG) axis in reproductive women. In this study, we examined the effects of dihydrotestosterone (DHT) on characteristic changes in rat anterior pituitary gland samples. DHT was administered to ovary-intact 6-week postnatal female rats for 7 days, after which the anterior pituitary glands were examined and compared with those in control rats. Estrous cyclicity was not drastically disrupted by DHT treatment. Common gonadotropin α subunit ( Cga ), luteinizing hormone β subunit ( Lhb ), and follicle-stimulating hormone (FSH) β subunit ( Fshb ) gene expression levels were not modulated by DHT treatment, while prolactin ( Prl ) gene expression was significantly repressed by DHT. Gonadotropin-releasing hormone (GnRH) receptor ( Gnrh-r ) gene expression was significantly inhibited by DHT, whereas pituitary adenylate cyclase-activating polypeptide (PACAP) receptor ( Pca1-r ) gene expression was increased by DHT. Gene expression levels of the receptors encoded by thyrotropin-releasing hormone ( Trh-r ) and kisspeptin ( Kiss1-r ) genes were unchanged. Expression of inhibin α subunit ( Inha ) and activin β A subunits ( Actba ) within the pituitary was inhibited by DHT treatment, while activin B subunit ( Actbb ) and follistatin ( Fst ) gene expression was unchanged by DHT. In mouse pituitary gonadotroph L β T2 cells, DHT did not modulate the gene expression of Gnrh-r , but it inhibited the expression of Inha and Actba subunits within the L β T2 cells. In rat prolactin-producing GH3 cells, DHT did not modulate prolactin gene expression, but it increased Pac1-r gene expression. The present observations suggest that DHT directly or indirectly affects the anterior pituitary gland and induces characteristic changes in hormone-producing cells., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Haruhiko Kanasaki et al.)
- Published
- 2022
- Full Text
- View/download PDF
193. FOXP4 inhibits squamous differentiation of atypical cells in cervical intraepithelial neoplasia via an ELF3-dependent pathway.
- Author
-
Matsumoto T, Iizuka T, Nakamura M, Suzuki T, Yamamoto M, Ono M, Kagami K, Kasama H, Wakae K, Muramatsu M, Horike SI, Kyo S, Yamamoto Y, Mizumoto Y, Daikoku T, and Fujiwara H
- Subjects
- DNA-Binding Proteins, Female, Forkhead Transcription Factors, Humans, Papillomaviridae, Proto-Oncogene Proteins c-ets, Sulfonamides, Transcription Factors, Carcinoma, Squamous Cell pathology, Papillomavirus Infections pathology, Uterine Cervical Neoplasms pathology, Uterine Cervical Dysplasia
- Abstract
Although the human papillomavirus (HPV) vaccine is effective for preventing cervical cancers, this vaccine does not eliminate pre-existing infections, and alternative strategies have been warranted. Here, we report that FOXP4 is a new target molecule for differentiation therapy of cervical intraepithelial neoplasia (CIN). An immunohistochemical study showed that FOXP4 was expressed in columnar epithelial, reserve, and immature squamous cells, but not in mature squamous cells of the normal uterine cervix. In contrast with normal mature squamous cells, FOXP4 was expressed in atypical squamous cells in CIN and squamous cell carcinoma lesions. The FOXP4-positive areas significantly increased according to the CIN stages from CIN1 to CIN3. In monolayer cultures, downregulation of FOXP4 attenuated proliferation and induced squamous differentiation in CIN1-derived HPV 16-positive W12 cells via an ELF3-dependent pathway. In organotypic raft cultures, FOXP4-downregulated W12 cells showed mature squamous phenotypes of CIN lesions. In human keratinocyte-derived HaCaT cells, FOXP4 downregulation also induced squamous differentiation via an ELF3-dependent pathway. These findings suggest that downregulation of FOXP4 inhibits cell proliferation and promotes the differentiation of atypical cells in CIN lesions. Based on these results, we propose that FOXP4 is a novel target molecule for nonsurgical CIN treatment that inhibits CIN progression by inducing squamous differentiation., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
- Published
- 2022
- Full Text
- View/download PDF
194. Usefulness of hybrid veno-arterial extracorporeal membrane oxygenation for lung ischemia-reperfusion injury after biventricular assist device implantation.
- Author
-
Mano A, Nishimura T, Ishii M, Murata T, Kawata M, and Kyo S
- Subjects
- Female, Humans, Lung, Extracorporeal Membrane Oxygenation, Heart-Assist Devices, Myocarditis, Reperfusion Injury
- Abstract
We experienced a case of fulminant myocarditis complicated by severe lung ischemia-reperfusion injury after switching from veno-arterial extracorporeal membrane oxygenation to biventricular assist device. We controlled lung blood flow by hybrid veno-arterial extracorporeal membrane oxygenation, which was established by modifying the biventricular assist device circuit without resternotomy, blood delivery to the pulmonary artery and blood removal from the left ventricle in addition to central veno-arterial extracorporeal membrane oxygenation, and accelerated lung recovery. The patient's lung damage and cardiac function were restored, and she completely recovered and was discharged without any complications. Regulation of lung blood flow is important and effective for lung ischemia-reperfusion injury after biventricular assist device implantation., (© 2022. The Japanese Society for Artificial Organs.)
- Published
- 2022
- Full Text
- View/download PDF
195. Early introduction of very small amounts of multiple foods to infants: A randomized trial.
- Author
-
Nishimura T, Fukazawa M, Fukuoka K, Okasora T, Yamada S, Kyo S, Homan M, Miura T, Nomura Y, Tsuchida S, Yajima S, Aoki S, Nakamura Y, Hosaka T, Hidaka H, Yamamori H, Inoue A, and Morimoto J
- Subjects
- Allergens, Arachis, Child, Emollients, Humans, Infant, Powders, Egg Hypersensitivity prevention & control, Food Hypersensitivity epidemiology, Food Hypersensitivity prevention & control
- Abstract
Background: We investigated whether multiple food allergies could be safely prevented by simultaneously administering very small amounts of multiple foods., Methods: Infants 3-4 months old with atopic dermatitis from 14 primary care pediatric clinics in Japan were enrolled in this randomized, placebo-controlled trial. The infants were administered either mixed allergenic food powder (MP) containing egg, milk, wheat, soybean, buckwheat, and peanuts, or placebo powder (PP). The amount of powder was increased in a stepwise manner on weeks 2 and 4, and continued until week 12. The occurrence of food allergy episodes after powder intervention was assessed at 18 months old. This trial was registered with the University Hospital Medical Information Network Clinical Trials Registry (number UMIN000027837)., Results: A total of 163 participants were randomly allocated to either the MP group (n = 83) or the PP group (n = 80). The incidence of food allergy episodes by 18 months was significantly different between the MP and PP groups (7/83 vs. 19/80, respectively; risk ratio 0.301 [95% CI 0.116-0.784]; P = 0.0066). Egg allergies were reduced in the MP group. In addition, food allergy episodes from any of the other five foods were significantly reduced, although the reductions in those due to individual foods were not significant., Conclusions: Gradually increasing the intake of very small amounts of multiple foods in early infancy can safely reduce the incidence of egg allergies. Other foods may also suppress food allergies, but no definitive conclusions could be reached., (Copyright © 2022 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
196. Hyperandrogenism induces proportional changes in the expression of Kiss-1, Tac2, and DynA in hypothalamic KNDy neurons.
- Author
-
Okada H, Kanasaki H, Tumurbaatar T, Tumurgan Z, Oride A, and Kyo S
- Subjects
- Androgens metabolism, Animals, Female, Gonadotropin-Releasing Hormone genetics, Gonadotropin-Releasing Hormone metabolism, Gonadotropin-Releasing Hormone pharmacology, Hypothalamus metabolism, Kisspeptins genetics, Kisspeptins metabolism, Mice, Neurokinin B genetics, Neurokinin B metabolism, Neurokinin B pharmacology, Neurons metabolism, Rats, Tachykinins, Testosterone metabolism, Testosterone pharmacology, Dynorphins genetics, Dynorphins metabolism, Dynorphins pharmacology, Hyperandrogenism metabolism
- Abstract
Background: Kisspeptin released from Kiss-1 neurons in the hypothalamus plays an essential role in the control of the hypothalamic-pituitary-gonadal axis by regulating the release of gonadotropin-releasing hormone (GnRH). In this study, we examined how androgen supplementation affects the characteristics of Kiss-1 neurons., Methods: We used a Kiss-1-expressing mHypoA-55 cell model that originated from the arcuate nucleus (ARC) of the mouse hypothalamus. These cells are KNDy neurons that co-express neurokinin B (NKB) and dynorphin A (DynA). We stimulated these cells with androgens and examined them. We also examined the ARC region of the hypothalamus in ovary-intact female rats after supplementation with androgens., Results: Stimulation of mHypoA-55 cells with 100 nM testosterone significantly increased Kiss-1 gene expression by 3.20 ± 0.44-fold; testosterone also increased kisspeptin protein expression. The expression of Tac3, the gene encoding NKB, was also increased by 2.69 ± 0.64-fold following stimulation of mHypoA-55 cells with 100 nM testosterone. DynA gene expression in these cells was unchanged by testosterone stimulation, but it was significantly reduced at the protein level. Dihydrotestosterone (DHT) had a similar effect to testosterone in mHypoA-55 cells; kisspeptin and NKB protein expression was significantly increased by DHT, whereas it significantly reduced DynA expression. In ovary-intact female rats, DTH administration significantly increased the gene expression of Kiss-1 and Tac3, but not DynA, in the arcuate nucleus. Exogenous NKB and DynA stimulation failed to modulate Kiss-1 gene expression in mHypoA-55 cells. Unlike androgen stimulation, prolactin stimulation did not modulate kisspeptin, NKB, or DynA protein expression in these cells., Conclusions: Our observations imply that hyperandrogenemia affects KNDy neurons and changes their neuronal characteristics by increasing kisspeptin and NKB levels and decreasing DynA levels. These changes might cause dysfunction of the hypothalamic-pituitary-gonadal axis., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
197. Effect of Muscle Loss but Not Fat Loss during Primary Debulking Surgery and Chemotherapy on Prognosis of Patients with Ovarian Cancer.
- Author
-
Nakayama N, Nakayama K, Ishibashi T, Katayama S, and Kyo S
- Abstract
Although the negative effect of muscle loss during invasive treatment has been widely reported in patients with cancer, its value in patients with ovarian cancer is not clear. Therefore, this study was conducted to clarify whether muscle loss during cytoreductive surgery and chemotherapy affects prognosis in patients with ovarian cancer. We retrospectively recruited 58 patients with ovarian cancer who underwent site reductive surgery and chemotherapy at Shimane University Hospital from March 2006 to November 2013 and for whom pre- and postoperative computed tomography were available. Skeletal muscle changes and fat mass volume during primary debulking surgery and chemotherapy were subsequently investigated at the level of the third lumbar vertebra. Muscle and fat mass loss occurred independently in half of the patients. Muscle loss, but not fat loss, was associated with disease-free survival ( p = 0.041 and p = 0.794, respectively) and poor overall survival ( p = 0.033 and p = 0.61, respectively). Cancer therapy is invasive and causes compositional changes in the body, such as muscle and fat loss. During cancer therapy, muscle loss, but not fat loss, may be associated with worse prognosis in ovarian cancer.
- Published
- 2022
- Full Text
- View/download PDF
198. Promising Therapeutic Impact of a Selective Estrogen Receptor Downregulator, Fulvestrant, as Demonstrated In Vitro upon Low-Grade Serous Ovarian Carcinoma Cell Lines.
- Author
-
Shanta K, Nakayama K, Hossain MM, Razia S, Ishibashi T, Ishikawa M, Yamashita H, Kanno K, Sato S, Nakayama S, Otsuki Y, and Kyo S
- Subjects
- Cell Line, Female, Fulvestrant pharmacology, Fulvestrant therapeutic use, Humans, Phosphatidylinositol 3-Kinases metabolism, Phosphatidylinositol 3-Kinases therapeutic use, Receptors, Estrogen metabolism, Cystadenocarcinoma, Serous drug therapy, Cystadenocarcinoma, Serous genetics, Cystadenocarcinoma, Serous metabolism, Ovarian Neoplasms drug therapy, Ovarian Neoplasms genetics, Peritoneal Neoplasms
- Abstract
Few studies have reported hormonal agent use in the treatment of low-grade serous ovarian carcinomas (LGSOCs), which are chemoresistant. Considering the need for novel effective therapies, we investigated the hormone receptor expression and hormonal inhibition efficacy in LGSOCs. Using immunohistochemistry, we assessed the estrogen receptor (ER) expression status in 33 cases of histologically confirmed serous ovarian tumors, including 10, 11, and 12 cases of LGSOCs, serous borderline tumors (SBTs), and serous cystadenomas (SCAs), respectively. The genetic background reported in our previous study was used in the current study. MPSC1 cells, which were established from LGSOCs, were used in cell proliferation assays. We observed a higher ER expression in LGSOCs and SBTs than in SCAs (70%, 81%, and 50%, respectively). Thus, LGSOCs and SBTs exhibit higher ER expression than SCAs. Moreover, the PIK3CA mutation positively correlated with ER expression in LGSOCs ( p = 0.0113). MPSC1 cells showed low ER expression on Western blotting. MPSC1 cell proliferation was significantly inhibited by fulvestrant (a selective ER downregulator). The activation of ER and PI3K/AKT signaling pathways may play an important role in LGSOC carcinogenesis. ER downregulation with fulvestrant or combination therapy with PI3K inhibitors is a possible novel treatment for patients with LGSOCs.
- Published
- 2022
- Full Text
- View/download PDF
199. JCS/JSCVS/JATS/JSVS 2021 Guideline on Implantable Left Ventricular Assist Device for Patients With Advanced Heart Failure.
- Author
-
Ono M, Yamaguchi O, Ohtani T, Kinugawa K, Saiki Y, Sawa Y, Shiose A, Tsutsui H, Fukushima N, Matsumiya G, Yanase M, Yamazaki K, Yamamoto K, Akiyama M, Imamura T, Iwasaki K, Endo M, Ohnishi Y, Okumura T, Kashiwa K, Kinoshita O, Kubota K, Seguchi O, Toda K, Nishioka H, Nishinaka T, Nishimura T, Hashimoto T, Hatano M, Higashi H, Higo T, Fujino T, Hori Y, Miyoshi T, Yamanaka M, Ohno T, Kimura T, Kyo S, Sakata Y, and Nakatani T
- Subjects
- Humans, Treatment Outcome, Defibrillators, Implantable, Heart Failure therapy, Heart-Assist Devices
- Published
- 2022
- Full Text
- View/download PDF
200. Clinical Landscape of PARP Inhibitors in Ovarian Cancer: Molecular Mechanisms and Clues to Overcome Resistance.
- Author
-
Kyo S, Kanno K, Takakura M, Yamashita H, Ishikawa M, Ishibashi T, Sato S, and Nakayama K
- Abstract
The survival of patients with advanced or recurrent ovarian cancer has improved tremendously in the past decade, mainly due to the establishment of maintenance therapy with poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis) after conservative chemotherapies. Despite their superior efficacy, resistance to PARPis has been reported, and patients with resistance have a much worse prognosis. Therefore, the development of novel treatment strategies to overcome PARPi resistance is urgently needed. The present review article focuses on the molecular mechanisms of how PARPis exert cytotoxic effects on cancer cells through DNA repair processes, especially the genetic background and tumor microenvironment favored by PARPis. Furthermore, currently available information on PARPi resistance mechanisms is introduced and discussed to develop a novel therapeutic approach against them.
- Published
- 2022
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.