Article
Genetics & Heredity
Neekesh Dharia, Guillaume Kugener, Lillian M. Guenther, Clare F. Malone, Adam D. Durbin, Andrew L. Hong, Thomas P. Howard, Pratiti Bandopadhayay, Caroline S. Wechsler, Iris Fung, Allison C. Warren, Joshua M. Dempster, John M. Krill-Burger, Brenton R. Paolella, Phoebe Moh, Nishant Jha, Andrew Tang, Philip Montgomery, Jesse S. Boehm, William C. Hahn, Charles W. M. Roberts, James M. McFarland, Aviad Tsherniak, Todd R. Golub, Francisca Vazquez, Kimberly Stegmaier
Summary: A pediatric cancer dependency map was created using genome-scale CRISPR-Cas9 loss-of-function screens in 82 pediatric cancer cell lines, revealing genetic dependencies across various tumor types. Contrary to the belief that pediatric cancers have fewer mutations, it was found that genetic dependencies in pediatric cancer cell lines are similarly complex as in adult models, indicating new therapeutic targets for childhood cancers.
Article
Pathology
Jared K. Woods, Hart G. Lidov, Keith L. Ligon, Sandro Santagata, Susan N. Chi, Kee Kiat Yeo, Sanda Alexandrescu
Summary: This study found immune activity in central nervous system germ cell tumors (GCTs) and suggested that the expression of PD-L1 and PD-1 may have implications for treatment. The choriocarcinoma subtype in non-germinomatous GCTs may benefit the most from immune checkpoint blockade.
Article
Oncology
Masatoshi Takagi, Chitose Ogawa, Tomoko Iehara, Yuki Aoki-Nogami, Eri Ishibashi, Minoru Imai, Toshimi Kimura, Masashi Nagata, Masato Yasuhara, Mitsuko Masutani, Kenichi Yoshimura, Daisuke Tomizawa, Atsushi Ogawa, Kan Yonemori, Aoi Morishita, Satoshi Miyamoto, Junko Takita, Tetsuro Kihara, Kiyoshi Nobori, Kazuhisa Hasebe, Fuyuki Miya, Sadakatsu Ikeda, Yoko Shioda, Kimikazu Matsumoto, Junya Fujimura, Shuki Mizutani, Tomohiro Morio, Hajime Hosoi, Ryuji Koike
Summary: This study evaluated the safety and efficacy of the PARP inhibitor olaparib in pediatric patients with solid tumors, recommending a daily dose for Phase 2 trials. Results showed that olaparib was well tolerated and had potential antitumor effects in DNA damage response-defective pediatric tumors.
Article
Oncology
Subha Perni, Beverly Moy, Ryan D. Nipp
Summary: The study found disparities in phase 1 versus phase 2/3 trial enrollment, with Black, Hispanic/Latino, and male patients being less likely to enroll in phase 1 trials compared to White patients. The findings suggest a need for targeted interventions to improve access to and education about phase 1 trials for Black and Hispanic/Latino patients.
Article
Immunology
Laia Gomez-Munoz, David Perna-Barrull, Josep M. Caroz-Armayones, Marta Murillo, Silvia Rodriguez-Fernandez, Aina Valls, Federico Vazquez, Jacobo Perez, Raquel Corripio, Luis Castano, Joan Bel, Marta Vives-Pi
Summary: The partial remission phase of type 1 diabetes is characterized by specific immunological biomarkers, including changes in the percentages of different types of T lymphocytes and inflammatory cells. In addition, certain immune cell percentages and the insulin dose at diagnosis can predict the occurrence of the partial remission phase.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Yi Que, Juan Wang, Jia Zhu, Na Li, Junting Huang, Suying Lu, Feifei Sun, Lian Zhang, Zijun Zhen, Li Zhang, Ruiqing Cai, Haixia Guo, Xiaofei Sun, Yizhuo Zhang
Summary: Limited experience of PD-1 antibody combined with other therapies in children was explored in a retrospective case study in Chinese expert centers. The study demonstrated antitumor activity of PD-1 antibody monotherapy in pediatric patients with Hodgkin lymphoma, while no objective response was observed in patients with melanoma or Burkitt lymphoma. The combination of PD-1 antibody with decitabine showed potential efficacy in pediatric patients with advanced embryonal rhabdomyosarcoma and lymphoepitheliomatoid-like carcinoma, with no severe treatment-related adverse events attributed to PD-1 antibody monotherapy in Asian pediatric patients.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, General & Internal
Chongkai Wang, Jaideep Sandhu, Ching Ouyang, Jian Ye, Peter P. Lee, Marwan Fakih
Summary: The study suggests that patients with MSS metastatic colorectal cancer without liver metastases may benefit from checkpoint inhibitors, while the presence of liver metastases could be associated with resistance to PD-1/PD-L1 treatment. More prospective studies are needed to further investigate the use of PD-1/PD-L1 inhibitors in MSS metastatic colorectal cancer patients without liver metastases.
Review
Oncology
Troy A. McEachron, Lee J. Helman
Summary: In recent years, there has been a significant shift in the field of pediatric cancer research, focusing on genetic and epigenetic drivers of disease, cellular origins of different pediatric cancers, disease models, the tumor microenvironment, and cellular immunotherapies.
Article
Clinical Neurology
Rostam Namdari, Constanza Luzon, Jay A. Cadieux, Jennifer Leung, Gregory N. Beatch
Summary: This study investigated the effect of food on the pharmacokinetics of XEN496, a formulation of ezogabine for pediatric use. The results showed that food delayed the onset of XEN496 but had no significant impact on its overall exposure. The safety profile of XEN496 was found to be similar to that of ezogabine tablets. Further studies are needed to evaluate the efficacy, safety, and pharmacokinetics of XEN496 in pediatric patients.
NEUROLOGY AND THERAPY
(2022)
Article
Pharmacology & Pharmacy
Yongshu Li, Bihui Huang, Zhichao Xue, Yunhua Gao, Zhenjian Zhuo
Summary: This article highlights the development of nucleic acid therapy in pediatric cancers as a potential way to improve treatment outcomes, which should attract more attention.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Oncology
Holly J. Meany, Brigitte C. Widemann, Pamela S. Hinds, Rochelle Bagatell, Suzanne Shusterman, Emily Stern, Nalini Jayaprakash, Cody J. Peer, William D. Figg, O. Morgan Hall, Tristan M. Sissung, Aerang Kim, Elizabeth Fox, Wendy B. London, Carlos Rodriguez-Galindo, Jane E. Minturn, Jeffrey S. Dome
Summary: This study evaluated the toxicity, pharmacokinetic, and pharmacogenomic profile of combining sorafenib and irinotecan in pediatric patients with solid tumors. The recommended dose was sorafenib 150 mg/m(2) twice daily with irinotecan 70 mg/m(2) daily x 5 days every 21 days. The combination regimen was well tolerated and resulted in prolonged disease stabilization, with no significant alterations in the pharmacokinetic profile of either agent. Patients were willing and able to report their subjective experiences with the treatment.
PEDIATRIC BLOOD & CANCER
(2021)
Article
Oncology
Karen M. Doersch, William B. Tabayoyong, Jathin Bandari
Summary: This study compared the occurrence of dose-limiting toxicities and serious adverse events in bladder cancer trials for intravesical therapies to other routes of administration. The results showed no significant difference in the subject-level dose-limiting toxicity rate between intravesical and other routes of administration, while the rate of serious adverse events was lower in the intravesical group.
Article
Oncology
Norikazu Masuda, Makiko Ono, Toru Mukohara, Hiroyuki Yasojima, Tatsunori Shimoi, Kokoro Kobayashi, Kenichi Harano, Makiko Mizutani, Maki Tanioka, Shunji Takahashi, Takahiro Kogawa, Takuya Suzuki, Shiori Okumura, Takao Takase, Reiko Nagai, Taro Semba, Zi-Ming Zhao, Min Ren, Kan Yonemori
Summary: This study evaluated the safety and efficacy of a liposomal formulation of eribulin, E7389-LF, in breast cancer patients. The results showed that E7389-LF had favorable antitumor activity, particularly in hormone receptor-positive breast cancer patients. Prophylactic pegfilgrastim may be considered for reducing the risk of neutropenia and febrile neutropenia.
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Medicine, General & Internal
G. K. Friedman, J. M. Johnston, A. K. Bag, J. D. Bernstock, R. Li, I Aban, K. Kachurak, L. Nan, K. D. Kang, S. Totsch, C. Schlappi, A. M. Martin, D. Pastakia, R. McNall-Knapp, S. Farouk Sait, Y. Khakoo, M. A. Karajannis, K. Woodling, J. D. Palmer, D. S. Osorio, J. Leonard, M. S. Abdelbaki, A. Madan-Swain, T. P. Atkinson, R. J. Whitley, J. B. Fiveash, J. M. Markert, G. Y. Gillespie
Summary: The study conducted a phase 1 trial of G207 in children and adolescents with recurrent or progressive supratentorial brain tumors, showing an acceptable adverse-event profile and evidence of responses. G207 was able to convert immunologically cold tumors to hot.
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Article
Clinical Neurology
Marco Carotenuto, Giovanni Messina, Maria Esposito, Claudia Santoro, Diego Iacono, Karen Spruyt
Summary: This study analyzed the sleep macrostructure of children with NF1 without neurocognitive co-morbidities and unidentified bright objects (UBOs). The results showed that NF1 children had reduced sleep duration, sleep efficiency, and stage N2 sleep percentage, as well as higher number of awakenings, wake after sleep onset, and respiratory events. These findings suggest that sleep evaluation can provide useful support for the diagnosis and treatment of NF1 and genetic neurodevelopmental disorders.
FRONTIERS IN NEUROLOGY
(2023)
Article
Genetics & Heredity
Amy R. Shikany, Laura Baker, Deborah L. Stabley, Katherine Robbins, Daniel Doyle, Karen W. Gripp, K. Nicole Weaver
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2020)
Article
Immunology
Elizabeth A. Kolb, Robin E. Buterbaugh, Carol L. Rinehart, Douglas Ensley, George A. Perry, Karim W. Abdelsalam, Christopher C. L. Chase
Article
Hematology
Stella M. Davies, Robert Iannone, Todd A. Alonzo, Yi-Cheng Wang, Robert Gerbing, Sandeep Soni, E. Anders Kolb, Soheil Meshinchi, Paul J. Orchard, Linda J. Burns, Shalini Shenoy, Wing Leung
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
(2020)
Article
Genetics & Heredity
Erin L. Crowgey, Nitin Mahajan, Wing Hing Wong, Anilkumar Gopalakrishnapillai, Sonali P. Barwe, E. Anders Kolb, Todd E. Druley
BMC MEDICAL GENOMICS
(2020)
Article
Oncology
E. Anders Kolb, Peter J. Houghton, Raushan T. Kurmasheva, Yael P. Mosse, John M. Maris, Stephen W. Erickson, Yuelong Guo, Beverly A. Teicher, Malcolm A. Smith, Richard Gorlick
PEDIATRIC BLOOD & CANCER
(2020)
Article
Oncology
Todd M. Cooper, Michael J. Absalon, Todd A. Alonzo, Robert B. Gerbing, Kasey J. Leger, Betsy A. Hirsch, Jessica Pollard, Bassem I. Razzouk, Richard Aplenc, E. Anders Kolb
JOURNAL OF CLINICAL ONCOLOGY
(2020)
Article
Oncology
Kelly D. Getz, Lillian Sung, Todd A. Alonzo, Kasey J. Leger, Robert B. Gerbing, Jessica A. Pollard, Todd Cooper, E. Anders Kolb, Alan S. Gamis, Bonnie Ky, Richard Aplenc
JOURNAL OF CLINICAL ONCOLOGY
(2020)
Article
Oncology
Douglas J. Harrison, Jonathan D. Gill, Michael E. Roth, Wendong Zhang, Beverly Teicher, Stephen Erickson, Greg Gatto, Raushan T. Kurmasheva, Peter J. Houghton, Malcolm A. Smith, Edward Anders Kolb, Richard Gorlick
PEDIATRIC BLOOD & CANCER
(2020)
Article
Biochemistry & Molecular Biology
Karen W. Gripp, Laura Baker, Katherine M. Robbins, Deborah L. Stabley, Gary A. Bellus, Verena Kolbe, Theresa Nauth, Georg Rosenberger
EUROPEAN JOURNAL OF HUMAN GENETICS
(2020)
Article
Oncology
Jonathan Gill, Wendong Zhang, Zhongting Zhang, Michael Roth, Douglas J. Harrison, Sudie Rowshan, Stephen Erickson, Gregory Gatto, Raushan Kurmasheva, Peter Houghton, Beverly Teicher, Malcolm A. Smith, E. Anders Kolb, Richard Gorlick
PEDIATRIC BLOOD & CANCER
(2020)
Article
Oncology
Andrew. D. J. Pearson, C. Michel Zwaan, E. Anders Kolb, Dominik Karres, Julie Guillot, Su Young Kim, Lynley Marshall, Sarah K. Tasian, Malcolm Smith, Todd Cooper, Peter C. Adamson, Elly Barry, Bouchra Benettaib, Florence Binlich, Anne Borgman, Erica Brivio, Renaud Capdeville, David Delgado, Douglas V. Faller, Linda Fogelstrand, Paula Goodman Fraenkel, Henrik Hasle, Delphine Heenen, Gertjan Kaspers, Mark Kieran, Jan-Henning Klusmann, Giovanni Lesa, Franca Ligas, Silvia Mappa, Hesham Mohamed, Andrew Moore, Joan Morris, Kerri Nottage, Dirk Reinhardt, Nicole Scobie, Stephen Simko, Thomas Winkler, Koen Norga, Gregory Reaman, Gilles Vassal
EUROPEAN JOURNAL OF CANCER
(2020)
Article
Oncology
Grace Nevil, Michael Roth, Jonathan Gill, Wendong Zhang, Beverly Teicher, Stephen W. Erickson, Gregory Gatto, Malcom Smith, E. Anders Kolb, Richard Gorlick
Summary: Research showed that eltrombopag did not significantly improve event-free survival (EFS) in 6 out of 6 models at moderate doses. However, at high doses, eltrombopag significantly prolonged EFS in 2 out of 2 models, with a small effect size. All tested models demonstrated progressive disease. While eltrombopag did not effectively inhibit osteosarcoma growth, it also did not stimulate tumor growth, suggesting it may be safely investigated as a supportive care agent to enhance platelet recovery post chemotherapy.
PEDIATRIC HEMATOLOGY AND ONCOLOGY
(2021)
Article
Genetics & Heredity
Deborah L. Stabley, Jennifer Holbrook, Mena Scavina, Thomas O. Crawford, Kathryn J. Swoboda, Katherine M. Robbins, Matthew E. R. Butchbach
Summary: Proximal spinal muscular atrophy (SMA) is an early-onset motor neuron disease caused by deletion or disabling mutations of survival motor neuron 1 (SMN1) and affected by the copy number of paralog SMN2. Array digital PCR (dPCR) can accurately and reliably measure SMN1 and SMN2 copy numbers and detect gene conversion events and partial deletions of SMN1. In SMA, higher SMN2 copy numbers are associated with milder disease severity.
Article
Pediatrics
Diksha Shrestha, George Xiangyun Ye, Deborah Stabley, Suhita Gayen nee Betal, Yan Zhu, Lisa Glazewski, Jennifer Holbrook, Meharpreet Sethi, Anne Hesek, Thomas H. Shaffer, Zubair H. Aghai, Sankar Addya, Deepthi Alapati
Summary: The study found that lung inflammation in preterm infants with BPD during the perinatal period leads to short- and long-term dysregulation of genes associated with pulmonary-specific immune cells, potentially increasing the risk of respiratory morbidities associated with environmental pathogens in children and adults with BPD.
PEDIATRIC RESEARCH
(2021)
Article
Oncology
Mareike Rasche, Martin Zimmermann, Emma Steidel, Todd Alonzo, Richard Aplenc, Jean-Pierre Bourquin, Heidrun Boztug, Todd Cooper, Alan S. Gamis, Robert B. Gerbing, Iveta Janotova, Jan-Henning Klusmann, Thomas Lehrnbecher, Nora Muehlegger, Nils V. Neuhoff, Naghmeh Niktoreh, Lucie Sramkova, Jan Stary, Katharina Waack, Christiane Walter, Ursula Creutzig, Michael Dworzak, Gertjan Kaspers, Edward Anders Kolb, Dirk Reinhardt
Summary: This study evaluated survival, response, and prognostic variables following relapse in children with acute myeloid leukemia (AML). Initial high-risk features and early relapse were found to predict post-relapse survival, while full hematopoietic recovery did not necessarily correlate with better survival outcomes. The data suggest the need for post-relapse risk stratification in future studies.