Article
Biochemistry & Molecular Biology
Karolina Losenkova, Akira Takeda, Symantas Ragauskas, Marc Cerrada-Gimenez, Maria Vahatupa, Simon Kaja, Marius L. Paul, Constanze C. Schmies, Georg Rolshoven, Christa E. Mueller, Jouko Sandholm, Sirpa Jalkanen, Giedrius Kalesnykas, Gennady G. Yegutkin
Summary: ATP and adenosine play important roles as signaling molecules in vascular remodeling, retinal functioning, and neurovascular coupling in the eye. This study characterized the whole pattern of purine metabolism in mouse and human eyes using various techniques, and identified major ocular ecto-nucleotidases involved in purinergic signaling. The study also highlighted the critical role of CD73 in maintaining the functional activity of retinal cells.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Review
Oncology
Maria Saigi, Oscar Mesia-Carbonell, David A. Barbie, Raquel Guillamat-Prats
Summary: CD73 and adenosine are playing important roles in lung cancer research. CD73 is an enzyme that is crucial for the production of adenosine and is found in various cells in the lungs, including immune cells. The expression of CD73 is increased in lung tumor cells, especially in non-small cell lung cancer. Researchers propose targeting CD73 and adenosine to enhance the effectiveness of immune checkpoint inhibitors. CD73 acts as a stop signal for immune cells fighting cancer, and blocking CD73 may amplify treatment effectiveness.
Article
Oncology
Erika Y. Faraoni, Kanchan Singh, Vidhi Chandra, Olivereen Le Roux, Yulin Dai, Ismet Sahin, Baylee J. O'Brien, Lincoln N. Strickland, Le Li, Emily Vucic, Amanda N. Warner, Melissa Pruski, Trent Clark, George Van Buren, Nirav C. Thosani, John S. Bynon, Curtis J. Wray, Dafna Bar-Sagi, Kyle L. Poulsen, Lana A. Vornik, Michelle I. Savage, Shizuko Sei, Altaf Mohammed, Zhongming Zhao, Powel H. Brown, Tingting Mills, Holger K. Eltzschig, Florencia McAllister, Jennifer M. Bailey-Lundberg
Summary: The microenvironment of PDAC is desmoplastic and immunosuppressive. CD73 is overexpressed in the tumor microenvironment and could be a target for immunotherapy.
Review
Chemistry, Medicinal
Bruna C. Galgaro, Liziane R. Beckenkamp, Martha van den M. Nunnenkamp, Vitoria G. Korb, Liliana I. S. Naasani, Katarzyna Roszek, Marcia R. Wink
Summary: Mesenchymal stem cells (MSCs) have various important functions in tissue homeostasis, damage repair, and immune modulation, and their therapeutic potential is closely related to the CD73/adenosine-mediated signaling pathway. Further research is needed to fully understand the role of CD73 and adenosine in the therapeutic functions of MSCs.
MEDICINAL RESEARCH REVIEWS
(2021)
Article
Chemistry, Medicinal
Ehesan U. Sharif, Jaroslaw Kalisiak, Kenneth Lawson, Dillon H. Miles, Eric Newcomb, Erick A. Lindsey, Brandon R. Rosen, Laurent P. P. Debien, Ada Chen, Xiaoning Zhao, Stephen W. Young, Nigel P. Walker, Norbert Straeter, Emma R. Scaletti, Lixia Jin, Guifen Xu, Manmohan R. Leleti, Jay P. Powers
Summary: Solid tumors often have high levels of extracellular ATP, which can be converted to adenosine by ectonucleotidases like CD73. Adenosine suppresses T-cell and NK-cell functions, promoting tumor immune evasion and poor prognosis. CD73 inhibition can restore immune function, and the development of potent and selective inhibitors shows promise in this area.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Jihyun Lee, Haeun Park, Sohyeon Moon, Jeong-Tae Do, Kwonho Hong, Youngsok Choi
Summary: CD73 is an enzyme that converts AMP into adenosine and is expressed on the surface of various cells, regulating immunity and inflammation. Research shows that the expression of CD73 in the uterus is dynamically regulated by estrogen and progesterone, with a synergistic effect of the two hormones.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Pengcheng Sun, Xiao Zheng, Xiaodong Li
Summary: CD73 is a promising immunotherapy target in GI cancer, and combining it with other therapies can improve prognosis and survival rate.
JOURNAL OF ONCOLOGY
(2022)
Article
Chemistry, Medicinal
Mirko Scortichini, Riham Mohammed Idris, Susanne Moschuetz, Antje Keim, Veronica Salmaso, Clemens Dobelmann, Paola Oliva, Karolina Losenkova, Heikki Irjala, Samuli Vaittinen, Jouko Sandholm, Gennady G. Yegutkin, Norbert Straeter, Anna Junker, Christa E. Mueller, Kenneth A. Jacobson
Summary: This study expands the structure-activity relationship of pyrimidine nucleotides as human CD73 inhibitors. By N-4-benzyloxy substitution, the inhibitory potency is greatly enhanced and functionality is added, making them potential anticancer drugs.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Liliana Dias, Daniela Pochmann, Cristina Lemos, Henrique B. Silva, Joana I. Real, Francisco Q. . Goncalves, Daniel Rial, Nelio Goncalves, Ana Patricia Simoes, Samira G. Ferreira, Paula Agostinho, Rodrigo A. . Cunha, Angelo R. . Tome
Summary: Increased ATP release and its extracellular catabolism through CD73 lead to the overactivation of A2AR in brain disorders. Blocking A2AR can alleviate mood and memory dysfunction caused by repeated stress, but it is unclear whether increased ATP release coupled to CD73-mediated adenosine formation contributes to A2AR overactivation under repeated stress. In this study, rats subjected to repeated stress showed increased release of ATP and increased CD73 density in the brain, and inhibiting CD73 activity attenuated mood and memory dysfunction. These findings suggest that modulating ATP release and CD73 activity could be potential strategies to alleviate the negative effects of repeated stress.
ACS CHEMICAL NEUROSCIENCE
(2023)
Article
Multidisciplinary Sciences
Harri Hakovirta, Juho Jalkanen, Eija Saimanen, Tiia Kukkonen, Pekka Romsi, Velipekka Suominen, Leena Vikatmaa, Mika Valtonen, Matti K. Karvonen, Maarit Venermo
Summary: The study aimed to assess the impact of IV IFN beta-1a on survival after emergency open surgery for a ruptured abdominal aortic aneurysm (RAAA) by up-regulating Cluster of Differentiation (CD73). The results showed no significant difference in survival between treatment groups, but an association between up-regulation of CD73 and survival. The most common adverse event related to IFN beta-1a was pyrexia.
SCIENTIFIC REPORTS
(2022)
Review
Pharmacology & Pharmacy
Gennady G. Yegutkin
Summary: Extracellular purinergic signaling, led by ATP, ADP, and adenosine, play a crucial role in immunomodulatory, thromboregulatory, angiogenic, and vasoactive activities. Recent studies have highlighted the complexity of regulatory mechanisms and the importance of considering the entire purinome in biological effects. Key enzymes in the adenosine metabolic network, especially purine-converting ectoenzymes, are emerging as novel targets for cancer and vascular therapies.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Neurosciences
Marija Adzic Bukvic, Danijela Laketa, Milorad Dragic, Irena Lavrnja, Nadezda Nedeljkovic
Summary: In neuroinflammatory states, functionally distinct eN/CD73 glycovariants appear, which may play a role in the development of the reactive astrocyte phenotype.
Review
Chemistry, Medicinal
Gustavo Machado das Neves, Luciano Porto Kagami, Ana Maria Oliveira Battastini, Fabricio Figueiro, Vera Lucia Eifler-Lima
Summary: Purinergic signaling is being explored as a potential therapeutic approach for cancer treatment. ATP acts as a chemotactic agent and has in vitro antineoplastic activity, while adenosine functions as an immunosuppressor and is associated with neoangiogenesis, vasculogenesis, and evasion from the immune system. Inhibitors of ecto-5'-NT can prevent tumor progression, lower adenosine concentrations, and impede cancer growth by preventing immune system evasion.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Ziyi Fu, Siqi Chen, Yueming Zhu, Donghong Zhang, Ping Xie, Qiao Jiao, Junlong Chi, Shipeng Xu, Yifan Xue, Xinghua Lu, Xinxin Song, Massimo Cristofanilli, William J. Gradishar, Kevin Kalinsky, Yongmei Yin, Bin Zhang, Yong Wan
Summary: We found that elevated CD73 levels due to aberrant turnover were associated with poor prognosis in immune-cold triple-negative breast cancers (TNBCs). TRIM21 was identified as the E3 ligase that controls CD73 degradation. Disrupting TRIM21 led to CD73 stabilization, enhanced CD73-catalyzed production of adenosine, and suppression of CD8+ T cell function. Replacement of specific residues on CD73 attenuated CD73 ubiquitylation and degradation, promoting tumor growth and impeding antitumor immunity.
Article
Chemistry, Medicinal
Paulina Mierzejewska, Noemi Di Marzo, Magdalena A. Zabielska-Kaczorowska, Iga Walczak, Ewa M. Slominska, Marialuisa Lavitrano, Roberto Giovannoni, Barbara Kutryb-Zajac, Ryszard T. Smolenski
Summary: The vascular endothelium is a crucial target for immune and thrombotic responses in xenotransplantation. This study evaluated the effects of simultaneous expression of three human genes on mouse endothelial function. The results showed that the simultaneous expression of these genes had beneficial effects on the biochemical and functional aspects of the endothelium, reducing inflammatory responses and improving endothelial permeability.
Article
Cardiac & Cardiovascular Systems
Kenichi Suda, Tetsuya Mitsudomi, Yasushi Shintani, Jiro Okami, Hiroyuki Ito, Takashi Ohtsuka, Shinichi Toyooka, Takeshi Mori, Shun-ichi Watanabe, Hisao Asamura, Masayuki Chida, Hiroshi Date, Shunsuke Endo, Takeshi Nagayasu, Ryoichi Nakanishi, Etsuo Miyaoka, Meinoshin Okumura, Ichiro Yoshino
Summary: This study investigated the impacts of EGFR mutation and mutation subtypes in early-stage lung cancer through a retrospective analysis of a Japanese nationwide database. The presence of EGFR mutation was significantly correlated with clinicopathologic factors and better prognosis. Patients with Exon 19 Del mutation exhibited a more aggressive phenotype and poorer prognosis compared to those with L858R mutation.
ANNALS OF THORACIC SURGERY
(2021)
Editorial Material
Oncology
Takashi Ohtsuka
ANNALS OF SURGICAL ONCOLOGY
(2021)
Review
Pathology
Masayuki Shimoda, Takashi Ohtsuka, Yasunori Okada, Yae Kanai
Summary: Proteolytic balance is crucial for tissue homeostasis maintenance. Dysregulated proteolysis in cancer, mainly from infiltrating stromal cells, plays a significant role in tumor growth and metastasis by impacting the extracellular matrix and cell signaling. Understanding the role of metalloproteinases from stromal cells in tumor microenvironment can provide insights into tumor progression.
PATHOLOGY INTERNATIONAL
(2021)
Article
Surgery
Takeo Nakada, Suguru Shirai, Yuko Oya, Yusuke Takahashi, Noriaki Sakakura, Takashi Ohtsuka, Hiroaki Kuroda
Summary: The study aimed to analyze the feasibility and risk factors associated with early mobilization after thoracoscopic lobectomy and segmentectomy. Results showed that the EM protocol was safe and useful for tubeless management, with a low frequency of orthostatic hypotension. Surgeons should actively prevent air leak to improve the success rate of early mobilization.
WORLD JOURNAL OF SURGERY
(2021)
Article
Cardiac & Cardiovascular Systems
Satoko Shiomi, Shohei Mori, Rintaro Shigemori, Hideki Matsudaira, Takashi Ohtsuka
Summary: Preoperative percutaneous drainage of giant mediastinal cystic teratoma can reduce the risks of respiratory failure or circulatory collapse, making general anesthesia induction safer. In cases of ruptured giant mediastinal teratoma, this method successfully reduces tumor volume and allows for smooth surgery.
GENERAL THORACIC AND CARDIOVASCULAR SURGERY
(2021)
Article
Cardiac & Cardiovascular Systems
Shohei Mori, Takamasa Shibazaki, Eriko Harada, Rintaro Shigemori, Daiki Kato, Hideki Matsudaira, Jun Hirano, Takashi Ohtsuka
Summary: This study retrospectively reviewed the operative records of patients undergoing thoracic cavity surgery and found that a blunted costophrenic angle is a predictor of complete pleural symphysis with moderate sensitivity and high specificity, accuracy.
GENERAL THORACIC AND CARDIOVASCULAR SURGERY
(2021)
Article
Oncology
Yasushi Shintani, Jiro Okami, Hiroyuki Ito, Takashi Ohtsuka, Shinichi Toyooka, Takeshi Mori, Shun-ichi Watanabe, Hisao Asamura, Masayuki Chida, Hiroshi Date, Shunsuke Endo, Takeshi Nagayasu, Ryoichi Nakanishi, Etsuo Miyaoka, Meinoshin Okumura, Ichiro Yoshino
Summary: The study investigated the clinical features and outcomes-related factors of MPLC patients using a Japanese database. It found differences between synchronous and metachronous MPLC patients in terms of gender, smoking status, lung function diseases, and histological types of lung cancer. This research provides valuable insights for MPLC diagnosis, prognosis, and postoperative management.
Article
Orthopedics
Takeo Nakada, Aiko Nakai, Yusuke Takahashi, Noriaki Sakakura, Takashi Ohtsuka, Hiroaki Kuroda
Summary: The study found that the combined use of intravenous analgesics and intercostal nerve blocks during thoracoscopic lobectomy can reduce postoperative pain without complications.
ASIAN JOURNAL OF ENDOSCOPIC SURGERY
(2022)
Article
Cardiac & Cardiovascular Systems
Takamasa Shibazaki, Shohei Mori, Yuki Noda, Yo Tsukamoto, Daiki Kato, Takeo Nakada, Mitsuo Yabe, Hideki Matsudaira, Jun Hirano, Takashi Ohtsuka
Summary: Resected lung lobe can affect the accuracy of the subsegment counting method, but not that of 3D-CT volumetry in predicting postoperative FEV1. Furthermore, 3D-CT volumetry can predict postoperative FEV1 independent of the resected lobe.
EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY
(2022)
Article
Oncology
Takashi Ohtsuka, Daiki Kato, Yo Tsukamoto, Takamasa Shibazaki, Takeo Nakada, Mitsuo Yabe, Jun Hirano
Summary: Esophagobronchial fistula formation is a severe complication of advanced thoracic malignancies. This case report describes the treatment of an 80-year-old man with advanced esophageal cancer complicated by EBF formation, who underwent placement of a partially covered SEMS and a silicone Y stent to stabilize the condition, leading to a stable postoperative course.
Article
Surgery
Yo Tsukamoto, Makoto Odaka, Takeo Nakada, Mitsuo Yabe, Eriko Harada, Tadashi Akiba, Naoki Toya, Takashi Ohtsuka
Summary: This study evaluated the feasibility of non-intubated video-assisted thoracoscopic surgery with local anesthesia for parapneumonic effusion and empyema resistant to conservative treatment. The study found some differences between patients who received local anesthesia and general anesthesia during surgery, but there were no significant differences in postoperative drainage duration, postoperative complication rate, and postoperative 30-day mortality rate.
ASIAN JOURNAL OF SURGERY
(2023)
Article
Oncology
Yosuke Matsuura, Mingon Mun, Yasushi Shintani, Jiro Okami, Hiroyuki Ito, Takashi Ohtsuka, Takeshi Mori, Shun-ichi Watanabe, Masayuki Chida, Shunsuke Endo, Ryoichi Nakanishi, Mitsutaka Kadokura, Hidemi Suzuki, Etsuo Miyaoka, Ichiro Yoshino, Hiroshi Date
Summary: This study retrospectively analyzed data from the Japanese Joint Committee of Lung Cancer Registry database and found that ALK rearrangement was associated with improved long-term outcomes in surgically resected lung adenocarcinoma patients. Multivariable analysis revealed that ALK rearrangement was an independent prognostic factor for improved overall survival. In the postrecurrence state, the use of ALK-tyrosine kinase inhibitors improved survival.
JOURNAL OF SURGICAL ONCOLOGY
(2023)
Article
Oncology
Hiroyuki Adachi, Aya Saito, Yasushi Shintani, Jiro Okami, Hiroyuki Ito, Takashi Ohtsuka, Takeshi Mori, Shun-ichi Watanabe, Masayuki Chida, Shunsuke Endo, Ryoichi Nakanishi, Mitsutaka Kadokura, Hidemi Suzuki, Etsuo Miyaoka, Ichiro Yoshino, Hiroshi Date
Summary: This study investigated the efficacy of adjuvant chemotherapy for elderly patients with completely resected stage I non-small-cell lung cancer based on real-world Japanese data using propensity score matching. The results showed that adjuvant chemotherapy did not provide significant benefits for elderly patients with completely resected stage I non-small-cell lung cancer.
JAPANESE JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Takeo Nakada, Yusuke Takahashi, Noriaki Sakakura, Katsuhiro Masago, Hiroshi Iwata, Takashi Ohtsuka, Hiroaki Kuroda
Summary: After using propensity score matched, there was no significant difference in recurrence-free survival (RFS) and overall survival (OS) between the LDCT and conventional CT groups for pathological stage I non-small-cell lung cancer (NSCLC) patients. Retrospective comparisons suggest no disadvantages of using LDCT for postoperative surveillance.
EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY
(2022)
Article
Cardiac & Cardiovascular Systems
Takeo Nakada, Yo Tsukamoto, Daiki Kato, Takamasa Shibazaki, Mitsuo Yabe, Jun Hirano, Takashi Ohtsuka
Summary: This study investigated the association between weight loss after lung cancer surgery and short-mid-term prognosis. The results showed that weight loss from 6 to 12 months after surgery was associated with poor prognosis. Ongoing nutritional management is important to prevent life-threatening weight loss in patients with predictive factors.
EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY
(2022)