Article
Cell Biology
Hao Wei, Matthew T. Harper
Summary: Various BH3 mimetics have different effects on platelet apoptosis, with some drugs triggering platelet death through mechanisms that are distinct from classical apoptosis pathways.
Article
Biochemistry & Molecular Biology
Natalia Rukoyatkina, Valentina Shpakova, Julia Sudnitsyna, Michael Panteleev, Stephanie Makhoul, Stepan Gambaryan, Kerstin Jurk
Summary: Our study demonstrated that curcumin exerts inhibitory effects on platelets through promoting procoagulant platelet formation instead of platelet apoptosis. Additionally, curcumin induced autophagy in platelets and inhibited platelet P-glycoprotein activity, contributing to its inhibitory effect on platelets through complex processes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Yuko Ikegawa, Christophe Combet, Mathieu Groussin, Vincent Navratil, Sabrina Safar-Remali, Takuya Shiota, Abdel Aouacheria, Sa Kan Yoo
Summary: Cells require stress sensing to initiate dormant cell death program. BH3-only proteins, recognized as essential stress sensors inducing apoptosis, have not been identified in Drosophila till now. However, we have identified the first Drosophila BH3-only protein, named sayonara, that induces apoptosis in a BH3 motif-dependent manner and interacts with Buffy and Debcl, BCL-2 homologous proteins. There exists a positive feedback loop between Sayonara-mediated caspase activation and autophagy.
Article
Oncology
Jiajia Yuan, Junzhe Song, Chao Chen, Xue Lv, Jie Bai, Jing Yang, Yuan Zhou
Summary: The combination of ruxolitinib and ABT-737 shows promise as a therapeutic strategy for patients with concurrent JAK2(V617F) and ASXL1 mutations in MPNs.
INVESTIGATIONAL NEW DRUGS
(2022)
Article
Oncology
Rui Cheng, Xiaolong Liu, Zheng Wang, Kunlong Tang
Summary: ABT-737 inhibits the proliferation and invasion of bladder cancer cells by inducing cell necrosis. ZBP1 and RIP3 play main roles in the cell necrosis induced by ABT-737, with RIP3 and ZBP1 directly inducing MLKL-mediated programmed cell necrosis.
MOLECULAR MEDICINE REPORTS
(2021)
Review
Biochemistry & Molecular Biology
Olga Shilova, Elena Shramova, Galina Proshkina, Sergey Deyev
Summary: This review discusses the use of protein toxins to target cancer cell receptors for precise therapy, along with the mechanisms of cytotoxic action of various toxins used in modern experimental oncology. The prospects of combined tumor therapy based on multimodal nanostructures are also explored.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Barbora Adamova, Kamila Rihova, Jana Pokludova, Petr Benes, Jan Smarda, Jarmila Navratilova
Summary: An acidic environment and hypoxia in cancer cells contribute to their resistance to therapy. The deregulation of the PI3K/Akt pathway is common in colon cancer. Combining Akt inhibitors with Bcl-2/Bcl-xL inhibitors could be an effective treatment strategy for colon cancer.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2023)
Article
Pharmacology & Pharmacy
Valentina Shpakova, Natalia Rukoyatkina, Nada Al Arawe, Anna Prilepskaya, Alexandra Kharazova, Iraida Sharina, Stepan Gambaryan, Emil Martin
Summary: This study reveals the molecular mechanisms of the 12-LOX inhibitor ML355 on platelets, demonstrating its antiplatelet and protective effects, which may be significant for antiplatelet and anticancer therapy.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Yuelin Guan, Kai Tu, Qiqian Huang, Feiyan Liu
Summary: In this study, it was found that Verticillin A could sensitize colon cancer to ABT-737-induced cell death by increasing the BIMEL/MCL-1 ratio and suppressing the MEK/ERK pathway. Additionally, upregulation of BIM protein levels facilitated BAX translocation and apoptosis induction. The potential application of Verticillin A as a MEK inhibitor in BH3-mimetic-based therapy was suggested based on these findings.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Oncology
Maria Josefina Quezada, Maria Elisa Picco, Maria Belen Villanueva, Maria Victoria Castro, Gaston Barbero, Natalia Brenda Fernandez, Edith Illescas, Pablo Lopez-Bergami
Summary: BCL2L10, a less studied protein from the Bcl-2 anti-apoptotic protein group, is abundantly and frequently expressed in melanoma cells and tumor samples, driven by STAT3-mediated transcription. It acts as a pro-survival factor by protecting cells from the cytotoxic effects of various drugs and inhibitors, suggesting that targeting BCL2L10 may enhance the clinical efficacy of other therapies for malignant melanoma.
Article
Medicine, Research & Experimental
Jiang Chang, Xilin Liu, Honglin Ren, Shiying Lu, Meng Li, Song Zhang, Ke Zhao, Hanxiao Li, Xiaoshi Zhou, Lixiong Peng, Zengshan Liu, Pan Hu
Summary: The study developed a new version of CCK2R-targeting immunotoxin GD9P, which showed higher antitumor activity against human colorectal cancer compared to the parental immunotoxin, suggesting its promising potential for immunotherapy targeting CCK2R-expressing colorectal malignancies.
MOLECULAR PHARMACEUTICS
(2021)
Article
Zoology
Bartlomiej Iwanski, Magdalena Mizerska-Kowalska, Mariola Andrejko
Summary: The cellular immune response of the greater wax moth Galleria mellonella to Pseudomonas aeruginosa exotoxin A was studied for the first time. Sublethal doses of exoA caused a significant decrease in total hemocyte count and a reduction in the number of granulocytes and plasmatocytes. Apoptotic and autophagic cell death features were observed in the exoA-challenged larvae, and flow cytometry analysis confirmed apoptosis induction through increased phosphatidylserine and active caspase 3-positive hemocytes. These findings contribute to our understanding of exotoxin A in P. aeruginosa infections in both insects and mammals, including humans.
JOURNAL OF INVERTEBRATE PATHOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Walter Douglas Fairlie, Erinna F. Lee
Summary: BCL-2, c-MYC and related proteins play crucial roles in normal cell functioning and are central to various cancers. Genetic lesions leading to deregulation of these proteins contribute to tumor development and survival depending on the cooperation between these protein families.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Dahwan Lim, So-Hui Choe, Sein Jin, Seulgi Lee, Younjin Kim, Ho-Chul Shin, Joon Sig Choi, Doo-Byoung Oh, Seung Jun Kim, Jinho Seo, Bonsu Ku
Summary: This study investigated the interaction between Bak and Pxt1 and revealed that Pxt1 functions as a proapoptotic factor that activates Bak. The findings provide a molecular basis for a novel pathway for the activation of apoptosis.
Article
Immunology
Pei Pi, Qingqiao Yin, Ling Xiao, Dan Luo
Summary: The study revealed the significant role of lncRNA Neat1 in MN, promoting the development of the disease by increasing apoptosis of renal tubular epithelial cells. This effect may be exerted by inhibiting the anti-apoptotic protein activity mediated by Noxa.
Article
Oncology
Luciana Gneo, Nagy Rizkalla, Rahul Hejmadi, Francis Mussai, Carmela de Santo, Gary Middleton
Summary: Monocytic myeloid-derived suppressor cells (M-MDSCs) are expanded in colorectal cancer (CRC) patients, inhibiting T cell proliferation. Blocking IL-10 released by HLA-DR- cells abrogates the suppressive function of M-MDSCs. Tumour conditioned media (TCM) reduces HLA-DR expression, increases IL-10 release, and promotes monocyte suppressive activity. TGF-beta in TCM drives monocyte immunosuppressivity and is enriched at the invasive margin of CRC.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2022)
Article
Critical Care Medicine
Benjamin A. Fisher, Tonny Veenith, Daniel Slade, Charlotte Gaskell, Matthew Rowland, Tony Whitehouse, James Scriven, Dhruv Parekh, Madhu S. Balasubramaniam, Graham Cooke, Nick Morley, Zoe Gabriel, Matthew P. Wise, Joanna Porter, Helen McShane, Ling-Pei Ho, Philip N. Newsome, Anna Rowe, Rowena Sharpe, David R. Thickett, Julian Bion, Simon Gates, Duncan Richards, Pamela Kearns
Summary: This study aimed to evaluate the efficacy of two drugs in hospitalized patients with COVID-19. The results showed that namilumab was able to reduce the inflammatory response, while infliximab did not show significant efficacy compared to usual care. Although there were some differences in adverse events and mortality rates, these differences were not significant.
LANCET RESPIRATORY MEDICINE
(2022)
Article
Oncology
Sakshi Tomar, Jingli Zhang, Manakamana Khanal, Jessica Hong, Abhilash Venugopalan, Qun Jiang, Manjistha Sengupta, Markku Miettinen, Nan Li, Ira Pastan, Mitchell Ho, Raffit Hassan
Summary: This study demonstrates that CAR T cells targeting mesothelin epitopes close to the cell membrane, such as hYP218, are highly effective against mesothelin-positive tumors, with increased persistence and tumor infiltration.
MOLECULAR CANCER THERAPEUTICS
(2022)
Article
Oncology
Jiajia Pan, Nan Li, Alex Renn, Hu Zhu, Lu Chen, Min Shen, Matthew D. Hall, Min Qian, Ira Pastan, Mitchell Ho
Summary: The cell surface proteoglycan GPC1 is overexpressed in multiple types of human cancers, including pancreatic cancer. In this study, researchers constructed GPC1-targeted immunotoxins and found that these immunotoxins can inhibit pancreatic tumor growth. Combining the immunotoxin with irinotecan further enhanced its efficacy.
MOLECULAR CANCER THERAPEUTICS
(2022)
Article
Multidisciplinary Sciences
Xiufen Liu, Masanori Onda, Nathan Watson, Raffit Hassan, Mitchell Ho, Tapan K. Bera, Junxia Wei, Anirban Chakraborty, Richard Beers, Qi Zhou, Asif Shajahan, Parastoo Azadi, Jingyu Zhan, Di Xia, Ira Pastan
Summary: Researchers have identified a monoclonal antibody that inhibits the shedding of the protein MSLN, which is highly expressed by cancer cells. The antibody binds to the protease-sensitive region of MSLN and CAR T cells produced with this antibody show superior antitumor activity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Oncology
Victoria Stavrou, Livingstone Fultang, Sarah Booth, Daniele De Simone, Arekdiusz Bartnik, Ugo Scarpa, Luciana Gneo, Silvia Panetti, Sandeep Potluri, Meaad Almowaled, Jonathan Barlow, Andris Jankevics, Gavin Lloyd, Andrew Southam, David A. Priestman, Paul Cheng, Warwick Dunn, Frances Platt, Hitoshi Endou, Charles Craddock, Karen Keeshan, Francis Mussai, Carmela De Santo
Summary: Acute myeloid leukaemia (AML) creates an immunosuppressive environment through induced arginine depletion. Serum amyloid A (SAA) in AML upregulates ARG2 expression, promotes cell viability, and activates iNKT cells, resulting in AML cell death. Therefore, stimulating iNKT cell activity has potential as an immunotherapy for AML.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Biotechnology & Applied Microbiology
Eleanor Bishop, Monika Dimitrova, Alexander Froggatt, Maria Estevez-Cebrero, Lisa C. D. Storer, Francis Mussai, Simon Paine, Richard G. Grundy, Madhumita Dandapani
Summary: Despite improvements in treatment and survival for paediatric cancers, brain tumours in children still have poor outcomes. This study investigates the potential of targeting the auxotrophy of extracellular arginine in paediatric brain tumours as a novel therapeutic approach. The results show that multiple types of paediatric brain tumours demonstrate arginine auxotrophy based on protein expression, suggesting that therapeutic arginine depletion may be a useful treatment strategy in these tumours.
BIOMED RESEARCH INTERNATIONAL
(2022)
Article
Oncology
Guillaume Joe Pegna, Min-Jung Lee, Cody J. Peer, Mehwish Ahmad, David J. Venzon, Yunkai Yu, Akira Yuno, Seth M. Steinberg, Liang Cao, William D. Figg, Renee N. Donahue, Raffit Hassan, Ira Pastan, Jane B. Trepel, Christine Alewine
Summary: The clinical trial of LMB-100 demonstrated some clinical efficacy but also revealed the potential intolerable side effect of capillary leak syndrome (CLS) when combined with nab-paclitaxel. Furthermore, LMB-100 treatment was found to cause systemic immune activation and associated inflammatory and immune changes.
Article
Hematology
Francis Mussai, Carmela De Santo, Paul Cheng, Ian F. Thomas, Cono Ariti, Laura Upton, Ugo Scarpa, Victoria Stavrou, Mia Sydenham, Alan K. Burnett, Steven K. Knapper, Priyanka Mehta, Mary F. McMullin, Mhairi Copland, Nigel H. Russell, Mike Dennis
Summary: The survival of older AML patients has been historically suboptimal regardless of the treatment regimen used. However, progress has been made in subgroups with favorable molecular or cytogenetic findings. This study investigated the efficacy of LDAC combined with recombinant arginase BCT-100 in older AML patients, and the overall response rate was slightly higher in the LDAC+BCT-100 group compared to the LDAC group, with no significant difference in overall or median survival observed between the two treatment arms.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Hematology
Silvia Panetti, Nicola McJannett, Livingstone Fultang, Sarah Booth, Luciana Gneo, Ugo Scarpa, Charles Smith, Ashley Vardon, Lisa Vettore, Celina Whalley, Yi Pan, Csilla Varnai, Hitoshi Endou, Jonathan Barlow, Daniel Tennant, Andrew Beggs, Francis Mussai, Carmela De Santo
Summary: Cancer cells and immune cells compete for limited amino acid availability, and T cells can be engineered to express amino acid transporters to enhance their proliferation and antitumor activity in the amino acid metabolic microenvironment of cancer.
Article
Biochemistry & Molecular Biology
Kevin M. Rattigan, Martha M. Zarou, Zuzana Brabcova, Bodhayan Prasad, Desiree Zerbst, Daniele Sarnello, Eric R. Kalkman, Angela Ianniciello, Mary T. Scott, Karen Dunn, Engy Shokry, David Sumpton, Mhairi Copland, Saverio Tardito, Johan Vande Voorde, Francis Mussai, Paul Cheng, G. Vignir Helgason
Summary: In order to fuel accelerated proliferation, leukaemic cells undergo metabolic deregulation, which leads to specific nutrient dependencies. Arginine is identified as an essential nutrient for primary human CML cells through an amino acid drop-out screen and pre-clinical models. Deprivation of arginine completely blocks the proliferation of CML CD34(+) cells and induces higher levels of apoptosis compared to cell lines. Moreover, treatment with the arginine-depleting enzyme, BCT-100, is highly effective in reducing the number of human leukaemic stem cells (LSCs) in a patient-derived xenograft model.
Article
Physiology
Kazuyoshi Yamamoto, Masahiro Okabe, Keiko Tanaka, Takashi Yokoo, Ira Pastan, Toshikazu Araoka, Kenji Osafune, Tomohiro Udagawa, Masahiro Koizumi, Taiji Matsusaka
Summary: This study clarifies why morphologically definitive apoptosis is rarely observed in podocytes in vivo. When caspase-3 is activated in podocytes, these cells are immediately detached from the glomerulus and lost in the urine before DNA fragmentation occurs. Detachment is facilitated by glomerular filtration. This phenomenon explains why podocytes in vivo rarely show TUNEL staining and never apoptotic bodies.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
Guannan Wang, Alok Kumar, Wanjun Ding, Preethi Korangath, Tapan Bera, Junxia Wei, Priya Pai, Kathleen Gabrielson, Ira Pastan, Saraswati Sukumar
Summary: The study demonstrated potent antitumor effects of intraductal injection of HB21(Fv)-PE40 on breast cancer, providing a strong preclinical foundation for conducting feasibility and safety trials in breast cancer patients.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Immunology
Ebtehag Maneta, Livingstone Fultang, Jemma Taylor, Matthew Pugh, William Jenkinson, Graham Anderson, Arri Coomarasamy, Mark D. Kilby, David M. Lissauer, Francis Mussai, Carmela De Santo
Summary: Recombinant G-CSF can induce a population of immunosuppressive ROS+ CD15(+)CD14(+) granulocytes. Strategies should be developed to schedule recombinant G-CSF to reduce its effects on T-cell therapies in future clinical studies.
CLINICAL & TRANSLATIONAL IMMUNOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Eleanor Bishop, Monika Dimitrova, Alexander Froggatt, Maria Estevez-Cebrero, Lisa C. D. Storer, Francis Mussai, Simon Paine, Richard G. Grundy, Madhumita Dandapani
Summary: The study found that extracellular arginine dependency is common in pediatric brain tumors, showing an auxotrophic signature. This discovery provides a new avenue for using arginine depletion as a treatment strategy.
BIOMED RESEARCH INTERNATIONAL
(2022)