Article
Cell Biology
Zhihui Liu, Xiyuan Zhang, Man Xu, Haiyan Lei, Jack F. Shern, Carol J. Thiele
Summary: The neural crest lineage regulatory transcription factors (TFs) play a crucial role in neuroblastoma (NB) by forming a core regulatory circuitry (CRC) to specify a specific tumor phenotype. This study focuses on the tumor suppressor CASZ1, which is silenced in NB tumor cells while the CRC components are highly expressed. The research findings indicate that the CRC component HAND2 directly represses CASZ1 expression. Restoring CASZ1 function upregulates noradrenergic neuronal genes and represses CRC component expression by remodeling enhancer activity, forming a negative feedback regulatory circuit with the established NB CRC to induce noradrenergic neuronal differentiation.
CELL DEATH & DISEASE
(2022)
Article
Oncology
Zhiwei Dong, Kok Siong Yeo, Gonzalo Lopez, Cheng Zhang, Erin N. Dankert Eggum, Jo Lynne Rokita, Choong Yong Ung, Taylor M. Levee, Zuag Paj Her, Cassie J. Howe, Xiaonan Hou, Janine H. van Ree, Shuai Li, Shuning He, Ting Tao, Karen Fritchie, Jorge Torres-Mora, Julia S. Lehman, Alexander Meves, Gina L. Razidlo, Komal S. Rathi, S. John Weroha, A. Thomas Look, Jan M. van Deursen, Hu Li, Jennifer J. Westendorf, John M. Maris, Shizhen Zhu
Summary: Research has shown that GAS7 gene is preferentially deleted in high-risk MYCN-driven neuroblastoma, and its deficiency accelerates metastasis in neuroblastoma models. Loss of GAS7 affects cell-cell interaction and contact among tumor cells, identifying a novel mechanism underlying tumor metastasis in MYCN-driven neuroblastoma.
Article
Oncology
Hasan Onur Caglar
Summary: This study aimed to identify potential tumor suppressor genes within commonly deleted regions in neuroblastoma tumors and explore the interaction network of proteins encoded by genes in these regions. The results showed that the selected genes in the deletion regions were downregulated and the hub genes identified may act as tumor suppressors in neuroblastoma tumorigenesis.
Article
Oncology
Marzia Ognibene, Patrizia De Marco, Loredana Amoroso, Davide Cangelosi, Federico Zara, Stefano Parodi, Annalisa Pezzolo
Summary: Neuroblastoma (NB), a tumor affecting the peripheral sympathetic nervous system, has unknown mechanisms determining its progression. This study found that loss of chromosome 10q is associated with poor prognosis in NB patients. Additionally, it identified a cluster of 75 deleted genes, including CCSER2, whose low expression is correlated with worse survival.
Article
Biology
Marion Rosello, Juliette Vougny, Francois Czarny, Marina C. Mione, Jean-Paul Concordet, Shahad Albadri, Filippo Del Bene
Summary: Researchers have successfully generated precise point mutations in zebrafish models using gene editing technology, mimicking oncogenic mutations in human genes and creating new disease models.
Article
Oncology
Chik Hong Kuick, Jia Ying Tan, Deborah Jasmine, Tohari Sumanty, Alvin Y. J. Ng, Byrrappa Venkatesh, Huiyi Chen, Eva Loh, Sudhanshi Jain, Wan Yi Seow, Eileen H. Q. Ng, Derrick W. Q. Lian, Shui Yen Soh, Kenneth T. E. Chang, Zhi Xiong Chen, Amos H. P. Loh
Summary: Our study found that mutations in chromosome 1 genes are common in 1p-intact neuroblastoma, but may not always disrupt the function of authentic 1p tumor suppressors. These findings suggest a complex interplay of 1p gene aberrations contributing to tumor suppressor inactivation in neuroblastoma.
Review
Cell Biology
Dana L. Woodstock, Morgan A. Sammons, Martin Fischer
Summary: p53 and p63, as transcription factors, regulate both shared and unique target genes to exert their tumor suppressive or oncogenic effects. The previous notion of strict competition between the two siblings needs to be reevaluated, as they can also collaborate towards a common goal.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Astrid K. Laut, Carmen Dorneburg, Axel Furstberger, Thomas F. E. Barth, Hans A. Kestler, Klaus-Michael Debatin, Christian Beltinger
Summary: CHD5, a tumor suppressor located at 1p36, is frequently lost or silenced in aggressive neuroblastoma and many adult cancers. Low expression of CHD5 is associated with stage 4 neuroblastoma and its forced expression inhibits key aspects of the metastatic cascade in vitro. Overexpression of CHD5 leads to reduced metastasis-related genes and gene sets, while known metastasis-suppressing genes are upregulated. Additionally, knockdown of PLCL1 and p53 reverses CHD5-induced inhibition of invasion and migration in vitro.
Article
Biochemistry & Molecular Biology
Mina Noura, Hidemasa Matsuo, Takahiko Yasuda, Shinobu Tsuzuki, Hitoshi Kiyoi, Fumihiko Hayakawa
Summary: TAL1 is frequently dysregulated in T-ALL, and its overexpression is associated with unfavorable clinical outcomes. This study found that the tumor suppressor KLF4 can suppress SE-driven TAL1 expression in T-ALL cells by inhibiting the formation of 5' TAL1 super-enhancer. A small molecule inducer of KLF4, APTO-253, exerts an anti-leukemic effect by targeting SE-driven TAL1 expression in T-ALL cells. Induction of KLF4 may be a promising strategy to control TAL1 expression and could serve as a novel treatment for T-ALL patients with poor prognosis.
Article
Oncology
Ana Costa, Cecile Thirant, Amira Kramdi, Cecile Pierre-Eugene, Caroline Louis-Brennetot, Orphee Blanchard, Didier Surdez, Nadege Gruel, Eve Lapouble, Gaelle Pierron, Deborah Sitbon, Herve Brisse, Arnaud Gauthier, Paul Freneaux, Mylene Bohec, Virginie Raynal, Sylvain Baulande, Renaud Leclere, Gabriel Champenois, Andre Nicolas, Didier Meseure, Angela Bellini, Aurelien Marabelle, Birgit Geoerger, Fatima Mechta-Grigoriou, Gudrun Schleiermacher, Laurie Menger, Olivier Delattre, Isabelle Janoueix-Lerosey
Summary: This study reveals that the immunocompromised microenvironment of neuroblastoma tumors is characterized by dysfunctional T cells and accumulation of immunosuppressive cells. The study provides a new and valuable data resource to better understand the neuroblastoma ecosystem and suggests novel therapeutic strategies targeting both tumor cells and components of the microenvironment.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Biniam Adane, Gabriela Alexe, Bo Kyung A. Seong, Diana Lu, Elizabeth E. Hwang, Denes Hnisz, Caleb A. Lareau, Linda Ross, Shan Lin, Filemon S. Dela Cruz, Melissa Richardson, Abraham S. Weintraub, Sarah Wang, Amanda Balboni Iniguez, Neekesh Dharia, Amy Saur Conway, Amanda L. Robichaud, Benjamin Tanenbaum, John M. Krill-Burger, Francisca Vazquez, Monica Schenone, Jason N. Berman, Andrew L. Kung, Steven A. Carr, Martin J. Aryee, Richard A. Young, Brian D. Crompton, Kimberly Stegmaier
Summary: The study shows that mutations in STAG2 can alter chromatin architecture and transcriptional programs, leading to a more aggressive cancer phenotype.
Article
Biochemistry & Molecular Biology
Ukjin Kim, Kwang Seok Kim, Jong-Kuk Park, Hong -Duck Um
Summary: The p53 tumor suppressor protein can regulate cell functions either as a transcription factor or by interaction with other proteins. The interaction between p53 and p21 was found to influence the transcriptional activity of p53. Furthermore, p21 was shown to play a role in regulating the expression of endogenous p53 targets.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Valentin Schmidt, Tobias Sieckmann, Karin M. Kirschner, Holger Scholz
Summary: In this study, it was found that WT1 regulates the HOXB9 gene in a bidirectional manner. Depending on the endogenous expression of WT1, forced changes in WT1 can stimulate or repress HOXB9, and the inhibitory effect of WT1 on transcription of HOXB9 involves BASP1. This regulation may play a role in kidney development and cancer progression.
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
(2021)
Article
Cell Biology
Kailing Zhou, Yu Sun, Dan Dong, Chenghai Zhao, Wei Wang
Summary: EMP3 acts as a potential tumor suppressor in breast cancer by inhibiting cell cycle progression, DNA repair, and stem-like properties, leading to enhanced sensitivity of breast cancer cells to DNA-damaging agents.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Matthew Martin, Rasika Mundade, Antja-Voy Hartley, Guanglong Jiang, Jiamin Jin, Steven Sun, Ahmad Safa, George Sandusky, Yunlong Liu, Tao Lu
Summary: ARMC4 is identified as a novel negative regulator of NF-kappa B, and may serve as a potential therapeutic target in colorectal cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Hematology
Hanny Al-Samkari, Kathryn Addonizio, Bertil Glader, D. Holmes Morton, Satheesh Chonat, Alexis A. Thompson, Kevin H. M. Kuo, Yaddanapudi Ravindranath, Heng Wang, Jennifer A. Rothman, Janet L. Kwiatkowski, Charles Kung, Penelope A. Kosinski, Hasan Al-Sayegh, Wendy B. London, Rachael F. Grace
Summary: Diagnosis of pyruvate kinase deficiency can be challenging, but the study found that the PK:HK ratio had excellent sensitivity for diagnosis. Furthermore, erythrocyte PK-R protein levels may be a useful prognostic biomarker for disease severity.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Letter
Dermatology
Connie S. Zhong, Carrie C. Coughlin, Elena B. Hawryluk, Kristen Hook, Stephen R. Humphrey, Lacey Kruse, Leslie Lawley, Pei-Chi Kao, Wendy B. London, Ashfaq A. Marghoob, Thuy L. Phung, Elena Pope, Lawrence F. Eichenfield, Jennifer T. Huang
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
(2021)
Article
Pathology
Asuka Kawano, Florette K. Hazard, Bill Chiu, Arlene Naranjo, Brian LaBarre, Wendy B. London, Michael D. Hogarty, Susan L. Cohn, John M. Maris, Julie R. Park, Julie M. Gastier-Foster, Naohiko Ikegaki, Hiroyuki Shimada
Summary: The study of 185 cases of stage 4S neuroblastoma revealed that patients with non-amplified MYCN mostly had a good prognosis, while overexpression of the MYC protein was associated with MYCN amplification, nucleolar hypertrophy, and poorer prognosis.
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
(2021)
Article
Medicine, General & Internal
Erica B. Esrick, Leslie E. Lehmann, Alessandra Biffi, Maureen Achebe, Christian Brendel, Marioara F. Ciuculescu, Heather Daley, Brenda MacKinnon, Emily Morris, Amy Federico, Daniela Abriss, Kari Boardman, Radia Khelladi, Kit Shaw, Helene Negre, Olivier Negre, Sarah Nikiforow, Jerome Ritz, Sung-Yun Pai, Wendy B. London, Colleen Dansereau, Matthew M. Heeney, Myriam Armant, John P. Manis, David A. Williams
Summary: This study confirms BCL11A inhibition as an effective approach for inducing HbF in sickle cell disease. Preliminary evidence suggests that shmik-based gene knockdown offers a favorable risk-benefit profile in treating sickle cell disease.
NEW ENGLAND JOURNAL OF MEDICINE
(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
Computer Science, Software Engineering
Abdul Wahid Khan, Maseeh Ullah Khan, Javed Ali Khan, Javed Khan, Wresham Gul
Summary: The study identified and captured 15 critical security challenges of big data on the cloud computing platform through a systematic literature review (SLR), and prioritized their significance using the fuzzy-TOPSIS approach. Additionally, the security challenges were categorized into four levels, and data secrecy issue was found to be the most prominent security challenge.
JOURNAL OF SOFTWARE-EVOLUTION AND PROCESS
(2021)
Article
Oncology
Guangyang Yu, Ying Pang, Mythili Merchant, Chimene Kesserwan, Vineela Gangalapudi, Abdalla Abdelmaksoud, Alice Ranjan, Olga Kim, Jun S. Wei, Hsien-Chao Chou, Xinyu Wen, Sivasish Sindiri, Young K. Song, Liqiang Xi, Rosandra N. Kaplan, Terri S. Armstrong, Mark R. Gilbert, Kenneth Aldape, Javed Khan, Jing Wu
Summary: The study found that TMB was not correlated with immune score in IDH-mutant gliomas, while in IDH-wildtype tumors, TMB was positively correlated with expressed neoantigens but inversely correlated with immune score. The Antigen Processing and Presentation (APP) score may have potential as a biomarker for immune therapy response in gliomas.
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)
Article
Oncology
Jerry T. Wu, Adam Cheuk, Kristine Isanogle, Christina Robinson, Xiaohu Zhang, Michele Ceribelli, Erin Beck, Paul Shinn, Carleen Klumpp-Thomas, Kelli M. Wilson, Crystal Mcknight, Zina Itkin, Hiroshi Sotome, Hiroshi Hirai, Elizabeth Calleja, Volker Wacheck, Brad Gouker, Cody J. Peer, Natalia Corvalan, David Milewski, Yong Y. Kim, William D. Figg, Elijah F. Edmondson, Craig J. Thomas, Simone Difilippantonio, Jun S. Wei, Javed Khan
Summary: Rhabdomyosarcoma (RMS) is a common pediatric soft tissue sarcoma. Futibatinib, an irreversible pan-FGFR inhibitor, shows efficacy in inhibiting the growth of RMS cell lines in vitro by targeting FGFR4. However, limited efficacy is observed in animal models, suggesting the need for alternative treatment strategies.
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
Barbara Degar, Patrick Campbell, Carl Allen, Michael Henry, Oussama Abla, Michelle Hermiston, David Ebb, Michael Hogarty, Stephan Ladisch, Rima Jubran, Kimo Stine, Ashish Kumar, Pei-Chi Kao, Wendy London, Eric Jacobsen, Carlos Rodriguez-Galindo
PEDIATRIC BLOOD & CANCER
(2021)
Article
Oncology
Karen D. Wright, Xiaopan Yao, Wendy B. London, Pei-Chi Kao, Lia Gore, Stephen Hunger, Russ Geyer, Kenneth J. Cohen, Jeffrey C. Allen, Howard M. Katzenstein, Amy Smith, Jessica Boklan, Kellie Nazemi, Tanya Trippett, Matthias Karajannis, Cynthia Herzog, Joseph Destefano, Jennifer Direnzo, Jay Pietrantonio, Lianne Greenspan, Danielle Cassidy, Debra Schissel, John Perentesis, Mitali Basu, Tomoyuki Mizuno, Alexander A. Vinks, Sanjay P. Prabhu, Susan N. Chi, Mark W. Kieran
Summary: Everolimus shows efficacy as an alternative treatment for pediatric patients with radiographically progressive low-grade glioma, with a well-tolerated profile. Some patients experienced toxicities, but overall survival rates were relatively high.
PEDIATRIC BLOOD & CANCER
(2021)
