Review
Medicine, General & Internal
Mark Roschewski, Louis M. M. Staudt, Wyndham H. H. Wilson
Summary: Burkitt's lymphoma is a rapidly proliferating lymphoma characterized by germinal-center B cells. Most patients can be cured through chemotherapy and prevention of tumor lysis, but relapse and involvement of the central nervous system have a poor prognosis.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Angelica Ferro, Dafni Graikioti, Emre Gezer, Constantinos M. M. Athanassopoulos, Muriel Cuendet
Summary: Although proteasome inhibitors have been used as the main treatment for multiple myeloma, patients often relapse and become resistant to drugs. Combining proteasome and histone deacetylase inhibitors has been found to be more effective, as it enhances anti-myeloma activity and improves patient outcomes. Hybrid molecules that combine the pharmacophores of entinostat and bortezomib have been synthesized and shown to have strong antiproliferative activity in multiple myeloma cells, including those resistant to bortezomib, as well as inhibiting histone deacetylase and proteasome activity.
Article
Oncology
Xiaoxi Zhou, Tong Ge, Tongjuan Li, Liang Huang, Yang Cao, Yi Xiao, Miao Zhen, Liting Chen, Jianfeng Zhou
Summary: The study evaluated the efficacy and safety of CAR19/22 T cell therapy in six refractory Burkitt's lymphoma cases, showing that three patients achieved an objective response and patients with bulky disease had poorer prognosis.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Vu Quang Lam, La Hoang Anh, Nguyen Van Quan, Tran Dang Xuan, Ichiro Hanamura, Kaori Uchino, Sivasundaram Karnan, Akiyoshi Takami
Summary: This study found that the ethyl acetate extract from Callerya speciosa root has strong antioxidant and cytotoxic activities, inhibiting the viability of multiple myeloma and mantle cell lymphoma cell lines and inducing cell apoptosis. The main compounds identified in the extract were isoflavones. These findings suggest that Callerya speciosa may be a promising natural source of antileukemia and antimyeloma agents.
Review
Biochemistry & Molecular Biology
Agata Tyczynska, Mikolaj Turski, Ewa Zarzycka, Jan Maciej Zaucha
Summary: Multiple myeloma (MM) is a disease characterized by uncontrolled proliferation of clonal plasma cells in the bone marrow. Central nervous system (CNS) plasmacytomas, a rare occurrence in MM patients, usually result from systemic disease progression. However, rare cases of localized disease progression to the CNS without signs of systemic progression have been reported. Here, we present a challenging case of an extramedullary plasmacytoma originating from the dura mater of the brain, mimicking a brain tumor. We review and discuss further treatment options for such rare clinical scenarios in relation to the treatment already undertaken.
Article
Oncology
Taylor D. Ellington, S. Jane Henley, Reda J. Wilson, Manxia Wu, Lisa C. Richardson
Summary: Plasma cell myeloma, solitary plasmacytoma, and extramedullary plasmacytoma primarily affect the elderly and are associated with excess body weight. The incidence rates of multiple myeloma have increased among adults in the United States from 2003 to 2016.
Article
Hematology
Tan-Huy Chu, Sung-Hoon Jung, Kihyun Kim, Jae Hoon Lee, Yeung-Chul Mun, Soo-Mee Bang, Dok Hyun Yoon, Ho Sup Lee, Chang-Ki Min, Je-Jung Lee
Summary: Plasmacytoma was frequently developed at MM relapse after upfront ASCT in patients with plasmacytoma at the time of diagnosis, and plasmacytoma at relapse was significantly associated with a poor prognosis.
ANNALS OF HEMATOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Leigh Deshotels, Firas M. M. Safa, Nakhle S. S. Saba
Summary: Although major progress has been made in mantle cell lymphoma (MCL) therapeutics, MCL still has a poor prognosis with a median survival of less than four years. Several genes, including NOTCH1 and NOTCH2, have been found to be mutated in MCL, leading to upregulation of genes involved in angiogenesis, cell cycle progression, and cell migration and adhesion. Mutated NOTCH genes are associated with aggressive features in MCL and inferior survival. This article discusses the role of NOTCH signaling in MCL biology and ongoing efforts for targeted therapeutic interventions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Dahai Liu, Fei Qi, Wei Liu, Justin Liu, Jun Wang, Dao-Qiang Lu, Yang Xun, Min-Min Chen, Xin Chen, Shu-Ting Yang, Wen-Qiao Jiao, Zong-Ye Li, Fang Liu, Hua Yang, Wen-Xing Li
Summary: This study explored the expression and function of cytokines in Hodgkin's lymphoma (HL), diffuse large B-cell lymphoma (DLBCL), and mantle cell lymphoma (MCL). The results showed shared immune functions and signal pathway damage in all three types of lymphoma, and these functions were related to cytokines. Furthermore, CXCL14 was identified as a key regulator affecting cell chemotaxis and migration functions.
Article
Biochemistry & Molecular Biology
Jimena Alvarez Freile, Natasha Ustyanovska Avtenyuk, Macarena Gonzalez Corrales, Harm Jan Lourens, Gerwin Huls, Tom van Meerten, Ewa Cendrowicz, Edwin Bremer
Summary: This study investigates the expression and therapeutic effects of CD24 and CD47, two immune checkpoints, in B-cell lymphoma. The results show that CD24 is associated with poor survival in MCL patients, while CD47 is associated with survival in DLBCL patients. CD24 antibody treatment exhibits potent phagocytic effects in MCL, but not in DLBCL.
Review
Oncology
Panruo Jiang, Aakash Desai, Haige Ye
Summary: Mantle cell lymphoma (MCL) is known as one of the most aggressive lymphoid tumors, but some cases may exhibit indolent behavior referred to as smoldering MCL (SMCL). Understanding the molecular mechanisms of indolent MCL, which differ significantly from classical MCL, can help differentiate these two types of lymphoma and guide appropriate treatment strategies.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2021)
Article
Oncology
Husain Yar Khan, Md. Hafiz Uddin, Suresh Kumar Balasubramanian, Noor Sulaiman, Marium Iqbal, Mahmoud Chaker, Amro Aboukameel, Yiwei Li, William Senapedis, Erkan Baloglu, Ramzi M. Mohammad, Jeffrey Zonder, Asfar S. Azmi
Summary: Targeting PAK4 and NAMPT using the small molecule inhibitor KPT-9274 can inhibit cell proliferation, deplete energy, and induce apoptosis in various NHL subtypes. KPT-9274 treatment shows potent anti-tumor effects in experimental models, suggesting its potential as a novel therapy for NHL.
Review
Biochemistry & Molecular Biology
Zoufang Huang, Vivek P. Chavda, Rajashri Bezbaruah, Hemant Dhamne, Dong-Hua Yang, Hong-Bing Zhao
Summary: Mantle cell lymphoma (MCL) is a subtype of Non-Hodgkin lymphoma characterized by translocation of Cyclin D1. Despite progress in understanding the causes and available treatments, MCL remains incurable. CAR-T cell therapy shows potential for treating B-cell malignancies and MCL.
Article
Oncology
Keman Zhang, Nand K. Roy, Yorleny Vicioso, Janghee Woo, Rose Beck, Marcos de Lima, Paolo Caimi, Daniel Feinberg, Reshmi Parameswaran
Summary: Mantle cell lymphoma (MCL) is an aggressive form of B cell non-Hodgkin's lymphoma that remains incurable under current treatment modalities. Research shows that B cell activating factor (BAFF) and BAFF receptor (BAFF-R) play important roles in the proliferation and survival of MCL cells, with high serum BAFF levels often correlated with poor drug response. Targeting BAFF-R using antibody therapy shows promise in overcoming drug resistance in MCL patients and improving treatment efficacy.
Review
Medicine, General & Internal
Elzbieta Szczepanek, Joanna Drozd-Sokolowska, Jacek Sokolowski, Anna Rzepakowska, Arkadiusz Moskwa, Jakub Pachla, Jakub Grzybowski, Katarzyna Woznica, Kazimierz Niemczyk, Krzysztof Jamroziak
Summary: The involvement of the larynx in plasma cell myeloma could present as solitary extramedullary plasmacytoma of the larynx or as infiltration of the larynx during systemic disease. This study analyzed cases of these conditions and found that patients with solitary extramedullary plasmacytoma were younger and had less common thyroid or cricoid cartilage involvement compared to patients with laryngeal involvement during systemic disease. Solitary extramedullary plasmacytoma had a better prognosis, while cartilage involvement negatively affected the outcome.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Shuling Zhang, Wei Shi, Edward S. Ramsay, Valery Bliskovsky, Adrian Max Eiden, Daniel Connors, Matthew Steinsaltz, Wendy DuBois, Beverly A. Mock
JOURNAL OF BIOLOGICAL CHEMISTRY
(2019)
Article
Biochemistry & Molecular Biology
Jun Li, Wendy Dubois, Vishal Thovarai, Zhijie Wu, Xingmin Feng, Tyler Peat, Shuling Zhang, Shurjo K. Sen, Giorgio Trinchieri, Jichun Chen, Beverly A. Mock, Neal S. Young
MOLECULAR CARCINOGENESIS
(2020)
Article
Oncology
Joy M. Gary, John K. Simmons, Jinfei Xu, Shuling Zhang, Tyler J. Peat, Nicholas Watson, Benjamin J. Gamache, Ke Zhang, Alexander L. Kovalchuk, Aleksandra M. Michalowski, Jin-Qiu Chen, Tuddow Thaiwong, Matti Kiupel, Snehal Gaikwad, Maudeline Etienne, R. Mark Simpson, Wendy Dubois, Joseph R. Testa, Beverly A. Mock
MOLECULAR CANCER THERAPEUTICS
(2020)
Article
Biochemistry & Molecular Biology
Jichun Chen, Shuling Zhang, Xingmin Feng, Zhijie Wu, Wendy Dubois, Vishal Thovarai, Sonia Ahluwalia, Shouguo Gao, Jinguo Chen, Tyler Peat, Shurjo K. Sen, Giorgio Trinchieri, Neal S. Young, Beverly A. Mock
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Oncology
Snehal M. Gaikwad, Zaw Phyo, Anaisa Quintanilla Arteaga, Sayeh Gorjifard, David R. Calabrese, Daniel Connors, Jing Huang, Aleksandra M. Michalowski, Shuling Zhang, Zheng-Gang Liu, John S. Schneekloth, Beverly A. Mock
Article
Biochemistry & Molecular Biology
Hualong Yan, Navdeep Malik, Young-Im Kim, Yunlong He, Mangmang Li, Wendy Dubois, Huaitian Liu, Tyler J. Peat, Joe T Nguyen, Yu-Chou Tseng, Gamze Ayaz, Waseem Alzamzami, King Chan, Thorkell Andresson, Lino Tessarollo, Beverly A. Mock, Maxwell P. Lee, Jing Huang
Summary: Metabolic regulation is crucial for the maintenance of pluripotency and survival of ESCs. Tfcp2l1 plays an unexpected role in promoting ESC survival by regulating fatty acid oxidation, and its deficiency leads to metabolic defects. The Tfcp2l1-Cpt1a-FAO axis contributes to the survival of ESCs under metabolic stress.
Letter
Oncology
Fumou Sun, Yan Cheng, Jesse D. Riordan, Adam Dupuy, Wendy Dubois, Michael Pisano, Jing Dong, Beverly Mock, Fenghuang Zhan, Parameswaran Hari, Siegfried Janz
Summary: The study utilized unbiased genetic forward screening in a genetically engineered mouse model of multiple myeloma to discover two novel myeloma genes: WDR26 and MTF2. These findings suggest that WDR26-CTLH and MTF2-PRC2 could be promising molecular targets for new approaches to myeloma treatment and prevention.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Shuling Zhang, Wendy Dubois, Xingmin Feng, Joe T. Nguyen, Neal S. Young, Beverly A. Mock
Summary: mTOR plays a critical role in early pre-B-cell development and survival, as demonstrated by conditional disruption of mTOR in developing mouse B cells leading to reduced pre-B-cell proliferation and survival, developmental block at the pre-B-cell stage, and lack of peripheral B cells.
MOLECULAR CARCINOGENESIS
(2022)
Article
Multidisciplinary Sciences
Kan Xie, Helmut Fuchs, Enzo Scifo, Dan Liu, Ahmad Aziz, Juan Antonio Aguilar-Pimentel, Oana Veronica Amarie, Lore Becker, Patricia da Silva-Buttkus, Julia Calzada-Wack, Yi-Li Cho, Yushuang Deng, A. Cole Edwards, Lillian Garrett, Christina Georgopoulou, Raffaele Gerlini, Sabine M. Hoelter, Tanja Klein-Rodewald, Michael Kramer, Stefanie Leuchtenberger, Dimitra Lountzi, Phillip Mayer-Kuckuk, Lena L. Nover, Manuela A. Oestereicher, Clemens Overkott, Brandon L. Pearson, Birgit Rathkolb, Jan Rozman, Jenny Russ, Kristina Schaaf, Nadine Spielmann, Adrian Sanz-Moreno, Claudia Stoeger, Irina Treise, Daniele Bano, Dirk H. Busch, Jochen Graw, Martin Klingenspor, Thomas Klopstock, Beverly A. Mock, Paolo Salomoni, Carsten Schmidt-Weber, Marco Weiergraber, Eckhard Wolf, Wolfgang Wurst, Valerie Gailus-Durner, Monique M. B. Breteler, Martin Hrabe de Angelis, Dan Ehninger
Summary: Current concepts about the biology of aging are mainly based on studies aiming at identifying factors that regulate lifespan. However, using lifespan as the only measure for aging may have limited value because it can be restricted by specific pathologies. In this study, large-scale phenotyping was used to analyze various markers in aging male mice. Lifetime profiles were established for each phenotype to determine when age-related changes become detectable relative to young adults. The effects of potential anti-aging interventions were also examined. Importantly, the study included young treated groups of animals, subjected to interventions before detectable age-related changes occurred. Many interventions influenced phenotypes before the onset of detectable age-related changes, but did not alter the rate of phenotypic change. Therefore, these interventions had limited effects on aging. Lifespan can be influenced by both physiological aging and specific pathologies associated with old age. The authors provide a resource for large-scale phenotyping of aging male mice at different time points, analyzing a wide range of phenotypes and molecular markers, including genetic and diet interventions that affect lifespan.
NATURE COMMUNICATIONS
(2022)
Review
Biotechnology & Applied Microbiology
George Alyateem, Heidi M. Wade, Aaron A. Bickert, Crystal C. Lipsey, Priya Mondal, MacKinzie D. Smith, Rania M. Labib, Beverly A. Mock, Robert W. Robey, Michael M. Gottesman
Summary: Despite the development of targeted anti-cancer drugs, the curative treatment of metastatic solid tumors remains challenging due to drug resistance. The use of CRISPR technology to generate cancer cell libraries carrying sgRNAs has shown promise in identifying novel mechanisms of drug resistance. Strategies using CRISPR knockout, activation, and inhibition screens, as well as specialized approaches to identify multiple contributing genes, offer a potential way to accelerate understanding of drug resistance in cancer.
CANCER GENE THERAPY
(2023)
Article
Medicine, Research & Experimental
Anju Kumari, Lisa Gesumaria, Yan-Jin Liu, V. Keith Hughitt, Xiaohu Zhang, Michele Ceribelli, Kelli M. Wilson, Carleen Klumpp-Thomas, Lu Chen, Crystal McKnight, Zina Itkin, Craig J. Thomas, Beverly A. Mock, David S. Schrump, Haobin Chen
Summary: Small cell lung cancer (SCLC) is a difficult-to-treat malignancy and current treatment options are limited. This study identified that mTOR inhibitors (mTORis) show the highest synergy with BET inhibitors (BETis) in SCLC, enhancing their antitumor activities both in vitro and in vivo. Mechanistically, BETis induce apoptosis in SCLC by activating the intrinsic apoptotic pathway, but also upregulate RSK3 to promote survival. However, mTORis block this survival signaling and augment the apoptosis induced by BET inhibition. Combination therapy of mTORis and BETis has potential for further evaluation in SCLC patients.
Article
Chemistry, Medicinal
Jung-Eun Park, Hobin Lee, Paola Oliva, Klara Kirsch, Bora Kim, Jong Il Ahn, Celeste N. Alverez, Snehal Gaikwad, Kristopher W. Krausz, Robert O'Connor, Ganesha Rai, Anton Simeonov, Beverly A. Mock, Frank J. Gonzalez, Kyung S. Lee, Kenneth A. Jacobson
Summary: Polo-like kinase 1 (Plk1) is an attractive target for anticancer drug discovery due to its widely upregulated activity in various human cancers. In addition to the kinase domain, the C-terminal noncatalytic polo-box domain (PBD) has emerged as an alternative target for developing inhibitors. Triazoloquinazolinone-derived inhibitors effectively block Plk1 with improved affinity and drug-like properties. Further derivatization is needed to improve the stability of these inhibitors for the development of therapeutics against Plk1-addicted cancers.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2023)
Meeting Abstract
Oncology
Dove-Anna Johnson, Michelle Pleet, Joshua Aden Welsh, Sean Cook, Jason Savage, Nooshin Mirza Nasiri, Kevin A. Camphausen, Kenneth D. Aldape, James L. Gulley, Beverly A. Mock, Jay A. Berzofsky, Steve Jacobson, Jennifer C. Jones
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Meeting Abstract
Oncology
Anju Kumari, Lisa Gesumaria, Patricia Fetsch, Markku Miettinen, Keith Hughitt, Beverly Mock, Craig Thomas, David S. Schrump, Haobin Chen
Meeting Abstract
Oncology
V. Keith Hughitt, Sayeh Gorjifard, Aleksandra M. Michalowski, John K. Simmons, Ryan Dale, Eric C. Polley, Jonathan J. Keats, Beverly A. Mock
Article
Oncology
Andra S. Martinikova, Miroslav Stoyanov, Anna Oravetzova, Yannick P. Kok, Shibo Yu, Jana Dobrovolna, Pavel Janscak, Marcel van Vugt, Libor Macurek
Summary: Oncogene-induced replication stress is a major cause of genome instability in cancer cells. This study reveals that increased activity of PPM1D exacerbates replication stress caused by cyclin E1 overexpression, leading to abnormal cell cycle progression and accumulation of DNA copy number alterations. Pharmacological inhibition of PPM1D can alleviate replication stress-induced genome instability.
MOLECULAR ONCOLOGY
(2024)
Article
Oncology
Alamelu G. Bharadwaj, Meghan E. McLean, Margaret L. Dahn, Hannah F. Cahill, Marie-Claire D. Wasson, Raj Pranap Arun, Olivia L. Walker, Brianne M. Cruickshank, Wasundara Fernando, Jaganathan Venkatesh, Penelope J. Barnes, Gillian Bethune, Gregory Knapp, Lucy K. Helyer, Carman A. Giacomantonio, David M. Waisman, Paola Marcato
Summary: ALDH1A3 regulates the plasminogen activation pathway to promote breast cancer metastasis. Co-expression of ALDH1A3 and tPA is associated with TNBC subtype, high tumor grade, and recurrent metastatic disease.
MOLECULAR ONCOLOGY
(2024)
Article
Oncology
Nayela N. Chowdhury, Yi Yang, Ananya Dutta, Michelle Luo, Zimu Wei, Sara R. Abrahams, Alexey S. Revenko, Fenil Shah, Lindsey A. Miles, Robert J. Parmer, Bas de Laat, Alisa S. Wolberg, James P. Luyendyk, Melissa L. Fishel, Matthew J. Flick
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal metastatic disease associated with robust activation of the coagulation and fibrinolytic systems. Primary fibrinolytic protease plasminogen promotes PDAC tumor growth and metastatic potential through engaging plasminogen receptors on tumor cells.
MOLECULAR ONCOLOGY
(2024)
Article
Oncology
Nuria Gendrau-Sanclemente, Agnes Figueras, Kristina Gracova, Alvaro Lahiguera, Elisenda Alsina-Sanchis, Juan A. Marin-Jimenez, August Vidal, Xavier Matias-Guiu, Sergi Fernandez-Gonzalez, Marc Barahona, Lola Marti, Jordi Ponce, Francesc Vinals
Summary: High-grade serous ovarian cancer (HGSOC), the deadliest gynecological malignancy, spreads through transcoelomic dissemination. This study reveals that platelet-derived growth factor receptor beta (PDGFRβ) is essential for the formation of tumorspheres in HGSOC. Inhibition of PDGFRβ blocks the clustering of ovarian cancer cells and prevents peritoneal dissemination.
MOLECULAR ONCOLOGY
(2024)