Article
Oncology
Ryo Tamura, Kosuke Yoshihara, Koji Matsuo, Nozomi Yachida, Ai Miyoshi, Kotaro Takahashi, Kentaro Sugino, Manako Yamaguchi, Yutaro Mori, Kazuaki Suda, Tatsuya Ishiguro, Shujiro Okuda, Teiichi Motoyama, Hirofumi Nakaoka, Akira Kikuchi, Yutaka Ueda, Ituro Inoue, Takayuki Enomoto
Summary: The study found that ovarian clear cell carcinoma (CCC) is often associated with a hypercoagulable state leading to higher incidence of thromboembolism, and elevated D-dimer levels are correlated with poor prognosis in CCC patients. CCC with high D-dimer levels exhibit distinct molecular characteristics involving inflammatory and immune-suppressive pathways.
GYNECOLOGIC ONCOLOGY
(2021)
Review
Oncology
Ryo Tamura, Kosuke Yoshihara, Takayuki Enomoto
Summary: Ovarian clear cell carcinoma (OCCC) is characterized by chemotherapy resistance and poor prognosis, especially in advanced cases. This review focuses on the association between cancer-associated hypercoagulation and molecular biology in OCCC. Additionally, potential drug therapies targeting hypercoagulation for OCCC are summarized. The review is expected to contribute to novel research and trials for the prevention, early detection, and treatment of OCCC.
Article
Hematology
Yohei Hisada, Kenison B. Garratt, Anaum Maqsood, Steven P. Grover, Tomohiro Kawano, Brian C. Cooley, Jonathan Erlich, Florian Moik, Matthew J. Flick, Ingrid Pabinger, Nigel Mackman, Cihan Ay
Summary: This study investigated the association of active Lys-PG in plasma and VTE in pancreatic cancer patients, as well as the impact of human pancreatic tumors expressing Lys-PG on venous thrombus resolution in mice. The results suggest that Lys-PG may contribute to the development of VTE in pancreatic cancer.
Article
Hematology
Toshihiro Gi, Aya Kuwahara, Atsushi Yamashita, Shuntaro Matsuda, Kazunari Maekawa, Sayaka Moriguchi-Goto, Yuichiro Sato, Yujiro Asada
Summary: We investigated the histopathological features of cancer-associated venous thromboembolism (VTE) in human autopsy cases. We found that vascular wall invasion or cancer cell clusters in thrombi might influence thrombogenesis of cancer-associated VTE. TF and podoplanin in cancer cells and in monocyte/macrophages may induce coagulation reactions and platelet aggregation. Neutrophil extracellular traps may play a role in the early stages of VTE, regardless of cancer status.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
Article
Oncology
Jennifer X. Ji, Dawn R. Cochrane, Gian Luca Negri, Shane Colborne, Sandra E. Spencer Miko, Lynn N. Hoang, David Farnell, Basile Tessier-Cloutier, Jutta Huvila, Emily Thompson, Samuel Leung, Derek Chiu, Christine Chow, Monica Ta, Martin Kobel, Lucas Feil, Michael Anglesio, Ellen L. Goode, Kelly Bolton, Gregg B. Morin, David G. Huntsman
Summary: Clear cell ovarian carcinoma (CCOC) has distinct proteomic differences compared with other subtypes of epithelial ovarian carcinoma, and potentially significant proteomic subgroups within CCOC, suggesting the possibility of stratified treatment for this cancer.
JOURNAL OF PATHOLOGY
(2022)
Article
Oncology
Michael-John Devilin, Rowan Miller, Florian Laforets, Panoraia Kotantaki, Dale W. Garsed, Rebecca Kristeleit, David D. Bowtell, Jacqueline McDermott, Eleni Maniati, Frances R. Balkwill
Summary: The tumor microenvironment (TME) of clear-cell ovarian cancer (CCOC) was analyzed in this study, revealing differences in immune cell populations, collagen matrix, and cytokine expression between different areas of the tumor. Advanced CCOC showed increased fibroblasts and a more complex collagen matrix compared to early CCOC. Differences in immune cell populations, collagen matrix, and cytokine expression were also observed between different genetic subtypes of CCOC. Increased infiltration of specific T cell subpopulations was associated with decreased overall survival.
CANCER IMMUNOLOGY RESEARCH
(2022)
Article
Medicine, Research & Experimental
Adam J. Ferrari, Priyanka Rawat, Hannah S. Rendulich, Akshaya Annapragada, Yasuto Kinose, Xiaoming Zhang, Kyle Devins, Anna Budina, Robert B. Scharpf, Marilyn A. Mitchell, Janos L. Tanyi, Mark A. Morgan, Lauren E. Schwartz, T. Rinda Soong, Victor E. Velculescu, Ronny Drapkin
Summary: Epigenetic aberrations, specifically the loss of histone H2B monoubiquitylation (H2Bub1), are associated with the development and progression of clear cell ovarian carcinoma (CCOC). The study identified hypermethylation of RNF40 as a likely mechanism underlying the loss of H2Bub1 in CCOC. Additionally, depletion of H2Bub1 was found to promote cell proliferation and clonogenicity in an endometriosis cell line.
Article
Oncology
Sarah A. Ackroyd, David Arguello, Pilar Ramos, Haider Mahdi, Adam ElNaggar, Ira Winer, Rob Holloway, Thomas Krivak, Nathaniel Jones, Valerie Galvan Turner, Thomas Herzog, Christina Chu, Jubilee Brown, Gina Mantia-Smaldone
Summary: This study analyzed ovarian and endometrial clear cell carcinomas using comprehensive sequencing technology and compared their molecular profiles to clear cell renal cell carcinoma. The results showed that these malignancies have different mutation profiles, but ovarian and endometrial clear cell carcinomas share similar molecular features. The study also suggested that a subset of ovarian clear cell carcinoma may benefit from immunotherapy. Evaluation: 7 out of 10.
GYNECOLOGIC ONCOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Tsukuru Amano, Atsushi Murakami, Takashi Murakami, Tokuhiro Chano
Summary: Ovarian clear cell carcinomas (OCCCs) are resistant to conventional anti-cancer drugs and often arise from endometriosis associated with strong oxidative stress. The oxidative stress tolerance properties are involved in the survival and cancer stemness of OCCC cells. Therapeutic approaches need improvement, with multi-combinatorial treatments expected to improve patient outcomes.
Article
Biochemistry & Molecular Biology
Hiroshi Maruoka, Tomohito Tanaka, Hikaru Murakami, Hiromitsu Tsuchihashi, Akihiko Toji, Misa Nunode, Atsushi Daimon, Shunsuke Miyamoto, Ruri Nishie, Shoko Ueda, Sousuke Hashida, Shinichi Terada, Hiromi Konishi, Yuhei Kogata, Kohei Taniguchi, Kazumasa Komura, Masahide Ohmichi
Summary: This study identified cancer-specific miRNAs in tissue-exudative extracellular vesicles (Te-EVs) of ovarian clear cell carcinomas (OCCs). The levels of these miRNAs were significantly decreased in postoperative serum samples, indicating their potential as biomarkers for the early diagnosis and detection of OCC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Deanna Glassman, Nicholas W. Bateman, Sanghoon Lee, Li Zhao, Jun Yao, Yukun Tan, Cristina Ivan, Kelly M. Rangel, Jianhua Zhang, Kelly A. Conrads, Brian L. Hood, Tamara Abulez, P. Andrew Futreal, Nicole D. Fleming, Vahid Afshar-Kharghan, George L. Maxwell, Thomas P. Conrads, Ken Chen, Anil K. Sood
Summary: Ovarian cancer patients with venous thromboembolism (VTE) have molecular differences compared to those without. VTE is associated with upregulated inflammatory and coagulation pathways, and correlated with the expression of platelet-derived growth factor subunit B (PDGFB) and extracellular proteins, namely collagens.
Article
Oncology
Chenchen Zhu, Jing Zhu, Lili Qian, Hanyuan Liu, Zhen Shen, Dabao Wu, Weidong Zhao, Weihua Xiao, Ying Zhou
Summary: OCCC often presents at an early stage and young age with a mildly elevated CA125. CA19-9, HE4, massive ascites, and positive lymph node are independent prognostic factors.
Article
Oncology
Derman Basaran, Thomas Boerner, Jessa Suhner, Dib Sassine, Ying Liu, Rachel N. Grisham, William P. Tew, Ginger J. Gardner, Oliver Zivanovic, Yukio Sonoda, Kara Long Roche, Dennis S. Chi, Nadeem R. Abu-Rustum, Gerald A. Soff, Elizabeth L. Jewell
Summary: The study aimed to determine the incidence of VTE in patients receiving neoadjuvant chemotherapy for ovarian cancer, finding that FIGO stage IV disease was the only factor associated with increased risk for new-onset VTE.
GYNECOLOGIC ONCOLOGY
(2021)
Article
Endocrinology & Metabolism
Kaitlyn E. Collins, Xiyin Wang, Yuliya Klymenko, Noah B. Davis, Maria C. Martinez, Chi Zhang, Kaman So, Aaron Buechlein, Douglas B. Rusch, Chad J. Creighton, Shannon M. Hawkins
Summary: Endometriosis is a risk factor for endometriosis-associated ovarian cancers. Analysis of OCCC samples with concurrent endometriosis revealed upregulation of cell cycle regulation and DNA replication pathways, and downregulation of cytokine receptor signaling and matrisome pathways. MiR-10a-5p was identified as a potentially oncogenic molecule with significant impact.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Oncology
Ling Han, Yali Chen, Ai Zheng, Hengxi Chen
Summary: In recent years, there has been increased attention to the relationship between neoadjuvant chemotherapy (NACT) in ovarian cancer and the incidence of venous thromboembolism (VTE). This study conducted a systematic review and meta-analysis to investigate the incidence of VTE during NACT and its associated risk factors. The analysis included 7 cohort studies with 1244 participants and found a pooled VTE rate of 13% during NACT, with body mass index identified as a risk factor.
AMERICAN JOURNAL OF CANCER RESEARCH
(2023)
Article
Hematology
Axel Rosell, Sebastian Havervall, Fien von Meijenfeldt, Yohei Hisada, Katherina Aguilera, Steven P. Grover, Ton Lisman, Nigel Mackman, Charlotte Thalin
Summary: The study found that COVID-19 patients have significantly higher levels of circulating EV TF activity compared to healthy controls. This increased activity was associated with disease severity, mortality, and markers like D-dimer, indicating a potential role of EV TF in driving thrombosis in COVID-19 patients.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Letter
Hematology
Yohei Hisada, Bernhard Moser, Tomohiro Kawano, Alexey S. Revenko, Jeff R. Crosby, Henri M. Spronk, Nigel Mackman
THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Hematology
Yohei Hisada, Kenison B. Garratt, Anaum Maqsood, Steven P. Grover, Tomohiro Kawano, Brian C. Cooley, Jonathan Erlich, Florian Moik, Matthew J. Flick, Ingrid Pabinger, Nigel Mackman, Cihan Ay
Summary: This study investigated the association of active Lys-PG in plasma and VTE in pancreatic cancer patients, as well as the impact of human pancreatic tumors expressing Lys-PG on venous thrombus resolution in mice. The results suggest that Lys-PG may contribute to the development of VTE in pancreatic cancer.
Review
Hematology
Steven P. Grover, Yohei M. Hisada, Raj S. Kasthuri, Brandi N. Reeves, Nigel Mackman
Summary: Cancer patients are at a higher risk of arterial and venous thrombotic events compared to the general population, with factors such as cancer site and stage, treatment-related factors, and cytotoxic effects of chemotherapeutic agents contributing to this increased risk. Despite advancements in targeted therapies, some anticancer agents still carry a risk of thrombosis, necessitating a better understanding of the mechanisms involved to develop effective treatment strategies.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Veterinary Sciences
Daniel Avenick, Linda Kidd, Stephanie Istvan, Fanglong Dong, Keith Richter, Nicole Edwards, Yohei Hisada, Jens J. N. Posma, Cherein Abdel Massih, Nigel Mackman
Summary: The study identified the accumulation of small procoagulant extracellular vesicles in canine packed red blood cells over time, with an earlier increase in concentration and procoagulant activity in units without leukocyte reduction. The procoagulant activity of the extracellular vesicles was attributed to phosphatidylserine, rather than tissue factor. Further research is needed to explore and understand the clinical relevance of these findings.
JOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE
(2021)
Article
Hematology
N. Mattila, Y. Hisada, B. Przybyla, J. Posma, A. Jouppila, C. Haglund, H. Seppanen, N. Mackman, R. Lassila
Summary: This study examined the association between CA 19-9 and thrombin generation in plasma from PDAC patients, finding that CA 19-9 levels were linked to several TG parameters. Additionally, some commercial sources of CA 19-9 were shown to enhance TG in SHP in patients prior to any pancreatic cancer treatments or signs of VTE.
THROMBOSIS RESEARCH
(2021)
Article
Multidisciplinary Sciences
Axel Rosell, Katherina Aguilera, Yohei Hisada, Clare Schmedes, Nigel Mackman, Hakan Wallen, Staffan Lundstrom, Charlotte Thalin
Summary: This study found that markers of neutrophil activation and NET formation can predict survival in terminal cancer patients, while markers of coagulation and fibrinolysis show weak or no correlations with these markers. This suggests that NETs may be linked to a poor prognosis through pathways independent of coagulation. Further research is needed to determine the utility of circulating neutrophil activation and NET markers as objective prognostic tools in advanced cancer.
SCIENTIFIC REPORTS
(2021)
Letter
Oncology
Nigel Mackman, Yohei Hisada, Sierra J. Archibald
Letter
Hematology
Nigel Mackman, Sierra J. Archibald, Yohei Hisada
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Review
Hematology
Nigel Mackman, Ana Teresa Azevedo Sachetto, Yohei Hisada
Summary: This review evaluates different methods for measuring tissue factor (TF) levels in plasma and extracellular vesicles (EVs). TF+ EVs in blood are increased in various diseases and are associated with thrombosis. Sensitivity is crucial for detecting the low levels of TF+ EVs in blood. The results indicate that measuring TF activity in EVs isolated from plasma using functional assays is more sensitive than antigen-based assays.
CURRENT OPINION IN HEMATOLOGY
(2022)
Review
Immunology
Yohei Hisada, Ana Teresa Azevedo Sachetto, Nigel Mackman
Summary: This review discusses the association between tissue factor and extracellular vesicles in various diseases, exploring their role in coagulation activation and survival. The source of tissue factor and extracellular vesicles in different diseases is also examined. The findings suggest that EVTF activity can serve as a biomarker to identify patients at risk of coagulopathy and mortality.
IMMUNOLOGICAL REVIEWS
(2022)
Editorial Material
Hematology
Nigel Mackman, Yohei Hisada
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
Article
Hematology
Tomohiro Kawano, Yohei Hisada, Steven P. P. Grover, Wyatt J. J. Schug, David S. S. Paul, Wolfgang Bergmeier, Nigel Mackman
Summary: Cancer patients have increased thrombosis and bleeding. Mouse models have been used to study the dysregulation of platelets and coagulation in cancer. Tumor-bearing mice exhibited chronic platelet activation, leading to thrombocytopenia, decreased receptor expression, and impaired platelet adhesive function.
THROMBOSIS AND HAEMOSTASIS
(2023)
Meeting Abstract
Hematology
Y. Hisada, S. J. Archibald, K. Bansal, S. Dwarampudi, A. K. Mullen, S. Bhatia, R. Bhatia, N. Mackman, R. Gangaraju
THROMBOSIS RESEARCH
(2022)
Article
Hematology
Sierra J. Archibald, Yohei Hisada, Victoria L. Bae-Jump, Nigel Mackman
Summary: This study evaluated the ability of the MACSPlex Exosome Kit to detect TF on EVs in plasma. The results showed that the MACSPlex Exosome Kit gives a nonspecific signal for TF and does not have the sensitivity to detect TF+ EVs in plasma.
RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS
(2022)