Article
Oncology
Puja Dey, Kentaro Nakayama, Sultana Razia, Masako Ishikawa, Tomoka Ishibashi, Hitomi Yamashita, Kosuke Kanno, Seiya Sato, Tohru Kiyono, Satoru Kyo
Summary: This study successfully developed an in vitro carcinogenic model of LGSOCs and found that the mutations of KRAS and PIK3CA play a causative role in LGSOC tumorigenesis. Simultaneous activation of the KRAS/ERK and PIK3CA/AKT signaling pathways is essential for LGSOC development.
Article
Multidisciplinary Sciences
Akira Yokoi, Mayu Ukai, Takao Yasui, Yasuhide Inokuma, Kim Hyeon-Deuk, Juntaro Matsuzaki, Kosuke Yoshida, Masami Kitagawa, Kunanon Chattrairat, Mikiko Iida, Taisuke Shimada, Yumehiro Manabe, I-Ya Chang, Eri Asano-Inami, Yoshihiro Koya, Akihiro Nawa, Kae Nakamura, Tohru Kiyono, Tomoyasu Kato, Akihiko Hirakawa, Yusuke Yoshioka, Takahiro Ochiya, Takeshi Hasegawa, Yoshinobu Baba, Yusuke Yamamoto, Hiroaki Kajiyama
Summary: Cancer cell-derived extracellular vesicles (EVs) could be potential targets for disease biomarkers due to their unique protein profiles. Analysis of small EVs (sEVs) and medium/large EVs (m/lEVs) revealed that both subtypes had distinct proteomic characteristics. Specific sEV proteins (FRa, Claudin-3, and TACSTD2) for high-grade serous ovarian carcinoma (HGSOC) were identified, while no candidates were found for m/lEVs. Additionally, a microfluidic device using polyketone-coated nanowires (pNWs) was developed for efficient sEV isolation and showed specific detectability in cancer patients and predicted clinical status.
Article
Reproductive Biology
Lu Zhang, Ruiting Fu, Ping Liu, Lijun Wang, Weihua Liang, Hong Zou, Wei Jia, Lin Tao
Summary: ETS transcription factor ETV5 plays an oncogenic role in high-grade serous ovarian cancer (HGSOC), with overexpression associated with poor prognosis. ETV5 promotes proliferation, migration, and invasion capabilities of HGSOC cells, making it a high-risk factor for HGSOC progression. It can be used as a clinically effective biomarker to determine HGSOC patient prognosis.
JOURNAL OF OVARIAN RESEARCH
(2021)
Article
Oncology
C. J. H. Kramer, L. Lanjouw, D. Ruano, A. ter Elst, G. Santandrea, N. Solleveld-Westerink, N. Werner, A. H. van Der Hout, C. D. de Kroon, T. van Wezel, L. P. Berger, M. Jalving, J. Wesseling, V. T. H. B. M. Smit, G. H. de Bock, C. J. van Asperen, M. J. E. Mourits, M. P. G. Vreeswijk, J. Bart, T. Bosse
Summary: This study analyzed the causal BRCA1/2 gene variants in different types of ovarian cancer tissues. The results showed that except for high-grade serous ovarian carcinoma, there were minimal BRCA1/2 PVs in other types of ovarian cancer. The study also identified some potentially misdiagnosed cases and conducted in-depth analysis of the pathogenic mechanism of BRCA1/2 variants. These findings suggest that histotype-directed sequencing may be more informative than universal sequencing.
JOURNAL OF PATHOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Kevin M. Wernke, Alina Tirla, Mengzhao Xue, Yulia Surovtseva, Fabian S. Menges, Seth B. Herzon
Summary: Colibactin is a genotoxic metabolite produced by commensal-pathogenic members of the human microbiome, potentially linked to tumorigenesis. Researchers synthesized and studied colibactin 742 (4), finding that it induces DNA interstrand-cross-links and activates DNA repair pathways, providing a new approach to study the genotoxic effects of colibactin.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Review
Biochemistry & Molecular Biology
Paula Punzon-Jimenez, Victor Lago, Santiago Domingo, Carlos Simon, Aymara Mas
Summary: High-grade serous ovarian carcinoma (HGSOC) is the most common form of epithelial ovarian carcinoma, and its early diagnosis still relies on traditional methods. Research on its etiopathogenesis provides new insights for finding early detection methods.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Elaine Stur, Sara Corvigno, Mingchu Xu, Ken Chen, Yukun Tan, Sanghoon Lee, Jinsong Liu, Emily Ricco, Daniel Kraushaar, Patricia Castro, Jianhua Zhang, Anil K. Sood
Summary: This study represents the first comprehensive analysis of spatial transcriptomics in high-grade serous ovarian carcinoma using intact tumor tissue. The study revealed extensive differences in tumor composition between poor and excellent responders to chemotherapy, with spatial interactions potentially playing a larger role in chemo-responsiveness.
Article
Biochemistry & Molecular Biology
Muriel Viau, Laurene Sonzogni, Melanie L. Ferlazzo, Elise Berthel, Sandrine Pereira, Larry Bodgi, Adeline Granzotto, Clement Devic, Beatrice Fervers, Laurent Charlet, Nicolas Foray
Summary: Studies suggest that metals may induce DSB through the nucleo-shuttling of ATM, affecting toxicity and carcinogenicity. The properties, concentration, and tissue type of different metals can all have an impact on this process.
Article
Oncology
Yasin Durmus, Mehmet M. Meydanli, Huseyin Akilli, Fulya Kayikcioglu, Kemal Gungorduk, Ozgur Akbayir, Salih Taskin, Husnu Celik, Ali Ayhan
Summary: This study evaluated nodal metastases in low-grade serous ovarian cancer patients and found that preoperative serum CA-125 levels and lymphovascular space invasion are independent predictors of nodal metastasis. Some patients initially classified as having limited disease to the ovary/ovaries were upstaged with a high percentage of lymph node metastases after surgical staging.
JOURNAL OF SURGICAL ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yiying Li, He Fei, Qiwang Lin, Fan Liang, Yanan You, Ming Li, Mengyao Wu, Ying Qu, Pengfei Li, Yan Yuan, Tong Chen, Hua Jiang
Summary: The study revealed that ZEB2 facilitates the invasive metastasis of EOC-CSLCs in HGSOC patients, and high ZEB2 expression is closely associated with metastasis rate and prognosis.
Article
Cell Biology
Tova M. Bergsten, Sarah E. Levy, Katherine E. Zink, Hannah J. Lusk, Melissa R. Pergande, Stephanie M. Cologna, Joanna E. Burdette, Laura M. Sanchez
Summary: This study discovered that a secreted protein called SPARC, produced by tumorigenic fallopian tube epithelial cells, enhances the release of norepinephrine (NE) from the ovary, influencing the primary metastasis of high grade serous ovarian cancer (HGSOC).
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Eros Azzalini, Giorgio Stanta, Vincenzo Canzonieri, Serena Bonin
Summary: Ovarian cancers are a group of neoplasms with distinct clinical, pathological, and molecular features. Among these, high-grade serous ovarian cancers (HGSOCs) are the most prevalent and exhibit high intratumor heterogeneity. The histological patterns and clonal evolution of HGSOCs have prognostic implications and are influenced by non-clonal intratumor heterogeneity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Qian Hao, Jiajia Li, Qinghua Zhang, Fei Xu, Bangxiang Xie, Hua Lu, Xiaohua Wu, Xiang Zhou
Summary: This study using single-cell transcriptomics analysis of HGSOC samples reveals new molecular features and potential therapeutic targets, which could advance the understanding and treatment of the disease.
CLINICAL AND TRANSLATIONAL MEDICINE
(2021)
Review
Oncology
Lauren Cobb, David Gershenson
Summary: Low-grade serous ovarian cancer is a rare subtype characterized by younger age at diagnosis, relative chemoresistance, and prolonged survival. The molecular features include estrogen and progesterone receptor positivity, MAPK pathway aberrations, and wild-type TP53 expression. Standard treatment includes cytoreductive surgery and platinum-based chemotherapy, but endocrine therapy and combination therapies targeting the MAPK pathway have been explored.
INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
(2023)
Article
Oncology
Zhao Cheng, Hasan Mirza, Darren P. Ennis, Philip Smith, Lena Morrill Gavarro, Chishimba Sokota, Gaia Giannone, Theodora Goranova, Thomas Bradley, Anna Piskorz, Michelle Lockley, Baljeet Kaur, Naveena Singh, Laura A. Tookman, Jonathan Krell, Jacqueline McDermott, Geoffrey Macintyre, Florian Markowetz, James D. Brenton, Iain A. McNeish
Summary: Late-stage and early-stage high-grade serous carcinomas (HGSCs) of the ovary exhibit highly similar patterns of mutation and copy-number alterations. However, late-stage HGSCs show distinct copy-number signature exposures consistent with whole-genome duplication. Further analysis is needed to determine whether these differences reflect genuine biological disparities between early-stage and late-stage disease or simply markers of evolutionary fitness over time.
CLINICAL CANCER RESEARCH
(2022)
Review
Cell Biology
Xuewei Zhang, Masaya Matsuda, Nobuo Yaegashi, Takeshi Nabe, Kazuyuki Kitatani
Article
Oncology
Xuewei Zhang, Masumi Ishibashi, Kazuyuki Kitatani, Shogo Shigeta, Hideki Tokunaga, Masafumi Toyoshima, Muneaki Shimada, Nobuo Yaegashi
Article
Biochemistry & Molecular Biology
Xuewei Zhang, Wataru Sakamoto, Daniel Canals, Masumi Ishibashi, Masaya Matsuda, Kentaro Nishida, Masafumi Toyoshima, Shogo Shigeta, Makoto Taniguchi, Can E. Senkal, Toshiro Okazaki, Nobuo Yaegashi, Yusuf A. Hannun, Takeshi Nabe, Kazuyuki Kitatani
Summary: Regulation of sphingolipid metabolism has a significant impact on cellular homeostasis and cancer progression. Dysregulation of ceramide-centered metabolism is associated with metastatic potential in ovarian cancer cells. Specifically, the CerS2-C-24:1-ceramide axis, possibly counteracted by neutral ceramidase, plays a key role in limiting cell motility and metastatic potential.
Article
Public, Environmental & Occupational Health
Atsushi Hozawa, Kozo Tanno, Naoki Nakaya, Tomohiro Nakamura, Naho Tsuchiya, Takumi Hirata, Akira Narita, Mana Kogure, Kotaro Nochioka, Ryohei Sasaki, Nobuyuki Takanashi, Kotaro Otsuka, Kiyomi Sakata, Shinichi Kuriyama, Masahiro Kikuya, Osamu Tanabe, Junichi Sugawara, Kichiya Suzuki, Yoichi Suzuki, Eiichi N. Kodama, Nobuo Fuse, Hideyasu Kiyomoto, Hiroaki Tomita, Akira Uruno, Yohei Hamanaka, Hirohito Metoki, Mami Ishikuro, Taku Obara, Tomoko Kobayashi, Kazuyuki Kitatani, Takako Takai-Igarashi, Soichi Ogishima, Mamoru Satoh, Hideki Ohmomo, Akito Tsuboi, Shinichi Egawa, Tadashi Ishii, Kiyoshi Ito, Sadayoshi Ito, Yasuyuki Taki, Naoko Minegishi, Naoto Ishii, Masao Nagasaki, Kazuhiko Igarashi, Seizo Koshiba, Ritsuko Shimizu, Gen Tamiya, Keiko Nakayama, Hozumi Motohashi, Jun Yasuda, Atsushi Shimizu, Tsuyoshi Hachiya, Yuh Shiwa, Teiji Tominaga, Hiroshi Tanaka, Kotaro Oyama, Ryoichi Tanaka, Hiroshi Kawame, Akimune Fukushima, Yasushi Ishigaki, Tomoharu Tokutomi, Noriko Osumi, Tadao Kobayashi, Fuji Nagami, Hiroaki Hashizume, Tomohiko Arai, Yoshio Kawaguchi, Shinichi Higuchi, Masaki Sakaida, Ryujin Endo, Satoshi Nishizuka, Ichiro Tsuji, Jiro Hitomi, Motoyuki Nakamura, Kuniaki Ogasawara, Nobuo Yaegashi, Kengo Kinoshita, Shigeo Kure, Akio Sakai, Seiichiro Kobayashi, Kenji Sobue, Makoto Sasaki, Masayuki Yamamoto
Summary: The study established a community-based cohort to assess the long-term impact of the Great East Japan Earthquake on disaster victims and gene-environment interactions on major disease incidence. Results showed that 70% of participants joined at health check-up sites, Type 1 survey participants were more likely to have psychological distress, women were more likely to have psychological distress than men, and coastal residents had higher levels of psychological distress compared to inland residents.
JOURNAL OF EPIDEMIOLOGY
(2021)
Article
Cell Biology
Tetsuya Terada, Masaya Matsuda, Miki Inaba, Junpei Hamaguchi, Naoki Takemoto, Yusuke Kikuoka, Yuko Inaka, Harumi Sakae, Kennosuke Hashimoto, Hayato Shimora, Kazuyuki Kitatani, Ryo Kawata, Takeshi Nabe
Summary: The study indicates that 4 years of SLIT is necessary to achieve sustained increases in Foxp3(+) Treg cells, which are closely associated with the efficacy of SLIT.
INFLAMMATION RESEARCH
(2021)
Article
Chemistry, Medicinal
Susumu Shinya, Kentaro Kawai, Atsushi Tarui, Yukiko Karuo, Kazuyuki Sato, Masaya Matsuda, Kazuyuki Kitatani, Naoki Kobayashi, Takeshi Nabe, Masato Otsuka, Masaaki Omote
Summary: In this study, the design and synthesis of cimetidine analogs and their inhibitory activity towards the human MATE1 transporter were investigated. The results showed that analogs with an unsubstituted guanidino group exhibited inhibitory activity, while compounds with a methylimidazole ring showed inhibition, and those with a phenyl ring did not. This suggests the importance of hydrogen bond formation in MATE1 inhibition.
CHEMICAL & PHARMACEUTICAL BULLETIN
(2021)
Article
Pharmacology & Pharmacy
Masaya Matsuda, Yoshiyuki Tanaka, Hayato Shimora, Naoki Takemoto, Miku Nomura, Ryogo Terakawa, Kennosuke Hashimoto, Harumi Sakae, Akira Kanda, Hiroshi Iwai, Kazuyuki Kitatani, Takeshi Nabe
Summary: This study aimed to develop a murine model of steroid-resistant asthma and investigate the role of group 2 innate lymphoid cells (ILC2s) in producing IL-5, a type-2 cytokine. The results showed that in steroid-resistant asthma, ILC2s produced larger amounts of IL-5 in response to IL-33/TSLP, and the up regulation of TSLP receptors on ILC2s may contribute to the pathogenic alteration. Treatment with anti-IL-5 monoclonal antibody in combination with dexamethasone effectively suppressed airway remodeling in the steroid-resistant model. Overall, IL-5 blockage could be a promising therapeutic strategy for steroid-resistant asthma.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Keiko Tamiya-Koizumi, Yurika Otoki, Kiyotaka Nakagawa, Reiji Kannagi, Naoki Mizutani, Motoshi Suzuki, Mamoru Kyogashima, Soichiro Iwaki, Mineyoshi Aoyama, Takashi Murate, Kazuyuki Kitatani, Takahisa Kuga, Yasuyoshi Mizutani, Akira Tokumura
Summary: Plasmalogen, localized in the raft of mammalian cell membranes, is involved in the storage of polyunsaturated fatty acids (PUFA) and is found to be more abundant in malignant cells surviving and growing in hypoxic conditions. In this study using liquid chromatography-tandem mass spectrometry, it was observed that the intracellular concentration of plasmalogen species containing a PUFA at the sn-2-position did not change for two days under hypoxic culture in human colorectal cancer-derived Caco2 cells. However, on the third day of hypoxia, there was a significant increase in ethanolamine plasmalogen and choline plasmalogen compared to the second day. This increase was suggested to be regulated by the up-regulation of mRNA of Ca2+-independent phospholipase A(2)beta and cytoplasmic phospholipase A(2)gamma, as well as the down-regulation of lysoplasmalogenase in Caco2 cells under hypoxia.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Immunology
Masaya Matsuda, Miki Inaba, Junpei Hamaguchi, Hiro Tomita, Miyu Omori, Hayato Shimora, Harumi Sakae, Kazuyuki Kitatani, Takeshi Nabe
Summary: IL-10 can suppress eosinophil and neutrophil infiltration by inhibiting the proliferation of ICAM-1+ and VCAM1+ pulmonary vascular endothelial cells, resulting in inhibition of airway hyperresponsiveness in steroid-insensitive asthmatic mice.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Microbiology
Masaya Matsuda, Seito Shimizu, Kazuyuki Kitatani, Takeshi Nabe
Summary: Extracellular vesicles play a crucial role in allergen immunotherapy by transforming into a suppressive phenotype of type 2 allergic inflammation.
Article
Cell Biology
Harumi Sakae, Yuri Ogiso, Masaya Matsuda, Hayato Shimora, Tye Deering, Todd E. Fox, Mark Kester, Takeshi Nabe, Kazuyuki Kitatani
Summary: This study investigated the therapeutic effects of ceramide nanoliposomes (CNL) on type 2 inflammation-based asthma. The results showed that CNL treatment significantly decreased airway remodeling and suppressed goblet cell hyperplasia induced by ovalbumin challenges. This suggests that CNL may have therapeutic effects on airway diseases like asthma.
Article
Genetics & Heredity
Soichi Ogishima, Satoshi Nagaie, Satoshi Mizuno, Ryosuke Ishiwata, Keita Iida, Kazuro Shimokawa, Takako Takai-Igarashi, Naoki Nakamura, Sachiko Nagase, Tomohiro Nakamura, Naho Tsuchiya, Naoki Nakaya, Keiko Murakami, Fumihiko Ueno, Tomomi Onuma, Mami Ishikuro, Taku Obara, Shunji Mugikura, Hiroaki Tomita, Akira Uruno, Tomoko Kobayashi, Akito Tsuboi, Shu Tadaka, Fumiki Katsuoka, Akira Narita, Mika Sakurai, Satoshi Makino, Gen Tamiya, Yuichi Aoki, Ritsuko Shimizu, Ikuko N. Motoike, Seizo Koshiba, Naoko Minegishi, Kazuki Kumada, Takahiro Nobukuni, Kichiya Suzuki, Inaho Danjoh, Fuji Nagami, Kozo Tanno, Hideki Ohmomo, Koichi Asahi, Atsushi Shimizu, Atsushi Hozawa, Shinichi Kuriyama, Nobuo Fuse, Teiji Tominaga, Shigeo Kure, Nobuo Yaegashi, Kengo Kinoshita, Makoto Sasaki, Hiroshi Tanaka, Masayuki Yamamoto
Summary: The Tohoku Medical Megabank (TMM) project has developed an integrated database called dbTMM to reveal gene-environment interactions underlying common diseases and estimate disease risk. This database incorporates individual whole-genome data and cohort/clinical data of 157,191 participants, enabling stratification by genetic and environmental factors for prospective analysis. dbTMM is expected to facilitate research on common diseases and improve disease risk prediction.
HUMAN GENOME VARIATION
(2021)
Meeting Abstract
Allergy
M. Matsuda, H. Tomita, M. Minakawa, Y. Takagi, M. Inaba, J. Hamaguchi, K. Kitatani, T. Nabe
Meeting Abstract
Allergy
T. Nabe, M. Matsuda, M. Nomura, N. Takemoto, R. Terakawa, K. Kitatani
Article
Medicine, Research & Experimental
Kazunori Fujiwara, Hiroaki Yazama, Ryohei Donishi, Satoshi Koyama, Takahiro Fukuhara, Kazuyuki Kitatani, Hideyuki Kataoka, Hiromi Takeuchi
YONAGO ACTA MEDICA
(2020)