Article
Neurosciences
Akhil Sharma, Viktoriia Bazylianska, Anna Moszczynska
Summary: PKO rats display a certain resistance to METH neurotoxicity, possibly mediated by lowered DA levels and downregulated mitochondria.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Neurosciences
Anne S. Gibson, Peter J. West, Kristen A. Keefe
Summary: The study aimed to determine the impact of METH on D1 receptor-dependent striatal LTP in mice. The results showed that METH-induced dopamine neurotoxicity impaired D1 receptor-dependent LTP in the dorsomedial striatum, but could be restored by administering bupropion.
PSYCHOPHARMACOLOGY
(2022)
Review
Neurosciences
Manqing Wu, Hang Su, Min Zhao
Summary: Chronic methamphetamine (METH) abuse may be associated with neurodegenerative changes in the human brain and an increased risk of Parkinson's disease (PD). Accumulation of alpha-synuclein in dopaminergic neurons of chronic METH users suggests a potential role of alpha-synuclein in METH-induced neurotoxicity.
NEUROTOXICITY RESEARCH
(2021)
Article
Multidisciplinary Sciences
Bobby Jones, Muthukumar Balasubramaniam, Joseph J. Lebowitz, Anne Taylor, Fernando Villalta, Habibeh Khoshbouei, Carrie Grueter, Brad Grueter, Chandravanu Dash, Jui Pandhare
Summary: The study reveals the essential role of proline biosynthesis in maintaining METH-induced glutamate homeostasis. METH exposure results in a significant upregulation of pyrroline-5-carboxylate synthase (P5CS), key enzyme for proline synthesis. Depletion of P5CS leads to an increase in glutamate levels upon METH exposure, emphasizing the protective mechanism to maintain glutamate homeostasis.
SCIENTIFIC REPORTS
(2021)
Article
Chemistry, Medicinal
Michela Ferrucci, Francesca Biagioni, Carla L. Busceti, Chiara Vidoni, Roberta Castino, Ciro Isidoro, Larisa Ryskalin, Alessandro Frati, Stefano Puglisi-Allegra, Francesco Fornai
Summary: The study investigates the role of autophagy in METH-induced toxicity of dopamine neurons, revealing that ongoing autophagy protects dopamine neurons and determines the refractoriness of cell bodies to METH-induced toxicity.
Review
Pharmacology & Pharmacy
Bi Deng, Zhirui Zhang, Huixuan Zhou, Xinran Zhang, Shuliang Niu, Xisheng Yan, Jie Yan
Summary: METH abuse is a significant global public health concern, and the mechanisms underlying its action are unclear. miRNAs play a role in the toxicity and addiction of METH after its use.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Neurosciences
Sujata Prasad, Wen S. Sheng, Shuxian Hu, Priyanka Chauhan, James R. Lokensgard
Summary: Repeated stimulation with viral antigens can lead to prolonged activation and proliferation of microglial cells, potentially resulting in neurotoxic consequences for the brain.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Neurosciences
Yarim Elideth De la Luz-Cuellar, Erick Josue Rodriguez-Palma, Urzula Franco-Enzastiga, Myrna Deciga-Campos, Francisco Mercado, Vinicio Granados-Soto
Summary: This study evaluated the role of D-1-like dopamine receptors in the reserpine-induced fibromyalgia-like pain model in female Wistar rats. The results showed that intrathecal dopamine and D-1-like receptor agonist induced nociceptive hypersensitivity in naive rats, while this effect was prevented by the D-1-like receptor antagonist. Additionally, transient silencing of D-1 and D-5 receptors significantly reduced reserpine-induced hypersensitivity in female rats. This work provides new insights about the involvement of the spinal dopaminergic D-1/D-5 receptors in reserpine-induced hypersensitivity in rats.
Article
Food Science & Technology
Bernardo Lopez-Torres, Irma Ares, Marta Martinez, Jorge-Enrique Maximiliano, Maria-Rosa Martinez-Larranaga, Arturo Anadon, Maria-Aranzazu Martinez
Summary: This study investigated the effects of Type II pyrethroid lambda-cyhalothrin on dopamine and serotonin synthesis in different brain regions of rats. The results showed that lambda-cyhalothrin decreased the levels of dopamine, serotonin, and metabolites in a dose-dependent manner, with the greatest decrease observed in the hippocampus and prefrontal cortex. Additionally, lambda-cyhalothrin altered the expression of genes related to dopamine and serotonin transportation, receptors, synthesis, and degradation. These findings suggest that lambda-cyhalothrin can induce neurotoxicity in the dopaminergic and serotoninergic pathways, potentially contributing to the development of neurodegenerative diseases.
FOOD AND CHEMICAL TOXICOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Diego R. R. Hernandez-Espinosa, Jenna R. R. Gale, Mia G. G. Scrabis, Elias Aizenman
Summary: Although the mechanisms determining microglial activation phenotypes are poorly understood, changes in cellular metabolism and intracellular pH regulation were found to play critical roles. Inhibiting the microglial voltage-gated proton channel 1 (Hv1) led to a shift from a pro-inflammatory to a neuroprotective phenotype, reducing the release of cytotoxic molecules and promoting neurotrophic factor production. This metabolic reprogramming was associated with increased NADH availability and decreased lactate production. Blocking Hv1 not only reduced inflammatory neurotoxicity but also provided neuroprotection against excitotoxic injury, suggesting the potential therapeutic application in inflammatory neurodegenerative disorders.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Mengru Zhang, Cheng Chen, Qingyan Peng, Xiaocong Wu, Ruiyi Zhou, Yuru Ma, Zhurong Zou
Summary: The stability-enhanced DnaJB1-tua2 can prevent the aggregation of Tau protein and maintain redox balance and protein homeostasis. In a MA-induced cognitive disorder mouse model, the expression of DnaJB1-tua2 in the hippocampus rescued the cognitive disorder and relieved the overactivated inflammatory response. Additionally, the escorting of DnaJB1-tua2 also reduced Tau neurofibrillary tangles and apoptotic neurons.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Article
Neurosciences
Kaori Masai, Keita Kuroda, Nami Isooka, Ryo Kikuoka, Shinki Murakami, Sunao Kamimai, Dengli Wang, Keyue Liu, Ikuko Miyazaki, Masahiro Nishibori, Masato Asanuma
Summary: The study showed that anti-HMGB1 mAb has neuroprotective effects against METH-induced dopaminergic neurotoxicity, suggesting the initial importance of HMGB1 in METH toxicity. However, blood-brain barrier disruption caused by METH injections was not suppressed by the mAb.
NEUROTOXICITY RESEARCH
(2021)
Article
Pharmacology & Pharmacy
B. Martins, J. P. Novo, E. Fonseca, R. Raposo, V. A. Sardao, F. Pereira, R. B. Oria, C. Fontes-Ribeiro, J. Malva
Summary: Methylmercury is a dangerous environmental contaminant that accumulates in the food chain and has neurotoxic properties. This study found that high concentrations of methylmercury can impair cell production, decrease the release of inflammatory mediators, and increase cell death.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Juliette Bedrossiantz, Marina Bellot, Pol Dominguez-Garcia, Melissa Faria, Eva Prats, Cristian Gomez-Canela, Raul Lopez-Arnau, Elena Escubedo, Demetrio Raldua
Summary: This study successfully established a zebrafish model of METH-induced neurotoxicity, demonstrating a concentration- and time-dependent decrease in dopamine, norepinephrine, and serotonin levels in METH-exposed fish. Behavioral changes included hyperactivity, positive geotaxis, and negative scototaxis, as well as social isolation, while transcriptional changes indicated alterations in gene expression related to neuronal injury.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
David W. Greening, Michael Notaras, Maoshan Chen, Rong Xu, Joel D. Smith, Lesley Cheng, Richard J. Simpson, Andrew F. Hill, Maarten van den Buuse
Summary: Studies have shown that chronic Meth abuse can lead to psychotic episodes resembling schizophrenia, with Brain-derived neurotrophic factor (BDNF) playing a crucial role in this process. Research on transgenic mice revealed that BDNF genetic variation significantly influences the long-term brain changes induced by Meth, indicating that drug-induced psychosis may be modulated at the molecular level by a single genetic locus.
MOLECULAR PSYCHIATRY
(2021)
Article
Public, Environmental & Occupational Health
Nicci Bartley, Megan C. Best, Barbara B. Biesecker, Alana Fisher, David Goldstein, Bettina Meiser, David M. Thomas, Mandy L. Ballinger, Phyllis Butow
Summary: This study explores the experience of uncertainty in advanced cancer patients when receiving comprehensive tumor genomic profiling (CTGP) results. The findings highlight the importance of clear, simple communication from healthcare providers (HCPs) and the support they provide in managing uncertainty.
PATIENT EDUCATION AND COUNSELING
(2022)
Article
Health Care Sciences & Services
Sabe Sabesan, Marie Malica, Chantal Gebbie, Clare Scott, David Thomas, John Zalcberg
Summary: This paper describes the steps and processes involved in the development and implementation of the Australasian Teletrial Model (ATM) by the Clinical Oncology Society of Australia. The implementation of ATM has improved access to clinical trials for patients in regional and rural areas, and enhanced collaboration between metropolitan and regional sites.
JOURNAL OF TELEMEDICINE AND TELECARE
(2023)
Article
Oncology
Megan C. Best, Nicci Bartley, Christine E. Napier, Alana Fisher, Mandy L. Ballinger, David M. Thomas, David Goldstein, Katherine Tucker, Barbara B. Biesecker, Phyllis Butow
Summary: This study investigated the experience of advanced cancer patients receiving comprehensive tumor genomic profiling (CGP) results. The findings suggest that patients face challenges in understanding the results and accepting the identified treatments. Support is needed to help patients understand the implications of testing and cope with non-actionable results.
SUPPORTIVE CARE IN CANCER
(2022)
Article
Multidisciplinary Sciences
Mrinal M. Gounder, Narasimhan P. Agaram, Sally E. Trabucco, Victoria Robinson, Richard A. Ferraro, Sherri Z. Millis, Anita Krishnan, Jessica Lee, Steven Attia, Wassim Abida, Alexander Drilon, Ping Chi, Sandra P. D'Angelo, Mark A. Dickson, Mary Lou Keohan, Ciara M. Kelly, Mark Agulnik, Sant P. Chawla, Edwin Choy, Rashmi Chugh, Christian F. Meyer, Parvathi A. Myer, Jessica L. Moore, Ross A. Okimoto, Raphael E. Pollock, Vinod Ravi, Arun S. Singh, Neeta Somaiah, Andrew J. Wagner, John H. Healey, Garrett M. Frampton, Jeffrey M. Venstrom, Jeffrey S. Ross, Marc Ladanyi, Samuel Singer, Murray F. Brennan, Gary K. Schwartz, Alexander J. Lazar, David M. Thomas, Robert G. Maki, William D. Tap, Siraj M. Ali, Dexter X. Jin
Summary: This study provides a comprehensive molecular analysis of sarcomas using targeted panel sequencing, identifying recurrent alterations and potential therapeutic targets. The findings shed light on the genetic landscape of sarcomas and may contribute to the development of precision-based therapies and improved clinical outcomes for patients with these rare cancers.
NATURE COMMUNICATIONS
(2022)
Review
Oncology
Silvia Stacchiotti, Anna Maria Frezza, George D. Demetri, Jean-Yves Blay, Jyoti Bajpai, Giacomo G. Baldi, Elizabeth H. Baldini, Robert S. Benjamin, Sylvie Bonvalot, Judith V. M. G. Bovee, Dario Callegaro, Paolo G. Casali, Sandra P. D'Angelo, Elizabeth J. Davis, Angelo P. Dei Tos, Elizabeth G. Demicco, Jayesh Desai, Palma Dileo, Mikael Eriksson, Hans Gelderblom, Suzanne George, Rebecca A. Gladdy, Mrinal M. Gounder, Abha A. Gupta, Rick Haas, Andrea Hayes, Peter Hohenberger, Kevin B. Jones, Robin L. Jones, Bernd Kasper, Akira Kawai, David G. Kirsch, Eugenie S. Kleinerman, Axel Le Cesne, Roberta Maestro, Javier Martin Broto, Robert G. Maki, Aisha B. Miah, Emanuela Palmerini, Shreaskumar R. Patel, Chandrajit P. Raut, Albiruni R. A. Razak, Damon R. Reed, Piotr Rutkowski, Roberta G. Sanfilippo, Marta Sbaraglia, Inga-Marie Schaefer, Dirk C. Strauss, Sandra J. Strauss, William D. Tap, David M. Thomas, Annalisa Trama, Jonathan C. Trent, Winette T. A. van der Graaf, Winan J. van Houdt, Margaret von Mehren, Breelyn A. Wilky, Christopher D. M. Fletcher, Alessandro Gronchi, Rosalba Miceli, Andrew J. Wagner
Summary: This article discusses the minimum requirements for conducting retrospective observational studies (ROS) in ultra-rare sarcomas (URS) to improve their quality and effectiveness. An expert panel reached a consensus on a set of recommendations through a survey and discussion, covering the use of ROS results, selection of participating centers, diagnosis and assessment methods, consistency of data monitoring policies, and more.
CANCER TREATMENT REVIEWS
(2022)
Review
Oncology
Matthew G. Krebs, Umberto Malapelle, Fabrice Andre, Luis Paz-Ares, Martin Schuler, David M. Thomas, Gilad Vainer, Takayuki Yoshino, Christian Rolfo
Summary: This review provides a practical overview for selecting the most appropriate liquid biopsy assay, focusing on circulating tumor DNA. The review found that liquid biopsy is increasingly being used clinically in advanced lung cancer, and ongoing research is identifying applications of circulating tumor DNA-based testing across a broad range of clinical settings.
Article
Oncology
Maya Kansara, Neeru Bhardwaj, Subotheni Thavaneswaran, Chang Xu, Jessica K. Lee, Lo-Bin Chang, Russell W. Madison, Frank Lin, Eugene Hsu, Vipul Kumar Patel, Alexey Aleshin, Geoffrey R. Oxnard, John Simes, Halla Nimeiri, David M. Thomas
Summary: There is a need to find biomarkers of early response that predict the benefit of immune checkpoint inhibitors (ICI). In this study, the researchers designed a personalized circulating tumor (ctDNA) assay based on tumor samples sequenced before treatment. They found that decline in ctDNA from baseline predicted improved overall survival (OS) and refined radiographic response calls. ctDNA clearance identified complete responders earlier than radiographic imaging. ctDNA response monitoring could be a personalized biomarker method to predict survival outcomes in diverse solid tumor histologies.
MOLECULAR ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Mandy L. Ballinger, Swetansu Pattnaik, Piyushkumar A. Mundra, Milita Zaheed, Emma Rath, Peter Priestley, Jonathan Baber, Isabelle Ray-Coquard, Nicholas Isambert, Sylvain Causeret, Winette T. A. van der Graaf, Ajay Puri, Florence Duffaud, Axel Le Cesne, Beatrice Seddon, Coonoor Chandrasekar, Joshua D. Schiffman, Andrew S. Brohl, Paul A. James, Jean-Emmanuel Kurtz, Nicolas Penel, Ola Myklebost, Leonardo A. Meza-Zepeda, Hilda Pickett, Maya Kansara, Nicola Waddell, Olga Kondrashova, John Pearson, Andrew P. Barbour, Shuai Li, Tuong L. Nguyen, Diane Fatkin, Robert M. Graham, Eleni Giannoulatou, Melissa J. Green, Warren Kaplan, Shyamsundar Ravishankar, Joseph Copty, Joseph E. Powell, Edwin Cuppen, Kristel van Eijk, Jan Veldink, Jin-Hee Ahn, Jeong Eun Kim, R. Lor Randall, Kathy Tucker, Ian Judson, Rajiv Sarin, Thomas Ludwig, Emmanuelle Genin, Jean-Francois Deleuze, Michelle Haber, Glenn Marshall, Murray J. Cairns, Jean-Yves Blay, David M. Thomas
Summary: Cancer genetics has focused on epithelial malignancies, but this study explores specific pathways related to sarcomas, rare malignancies derived from embryonic mesoderm. Germline sequencing of sporadic cases and healthy controls reveals two sarcoma-specific pathways involved in mitotic and telomere functions. Centrosome gene variants are linked to specific tumors, while heritable defects in the shelterin complex increase susceptibility to sarcomas, melanomas, and thyroid cancers. These findings highlight the role of heritable defects in mitotic and telomere biology in sarcoma risk.
Article
Oncology
Christine Y. Y. Lu, Vera Terry, David M. Thomas
Summary: Science has made significant progress in understanding the molecular basis of disease and developing effective treatments. However, the affordability of healthcare is becoming a crisis due to the success of science. The COVID-19 pandemic highlights the value of science in healthcare, as well as the tension between health and the economy. Drug development for smaller target populations contributes to the rising costs of healthcare.
NPJ PRECISION ONCOLOGY
(2023)
Article
Genetics & Heredity
Zornitza Stark, Tiffany Boughtwood, Matilda Haas, Jeffrey Braithwaite, Clara L. Gaff, Ilias Goranitis, Amanda B. Spurdle, David P. Hansen, Oliver Hofmann, Nigel Laing, Sylvia Metcalfe, Ainsley J. Newson, Hamish S. Scott, Natalie Thorne, Robyn L. Ward, Marcel E. Dinger, Stephanie Best, Janet C. Long, Sean M. Grimmond, John Pearson, Nicola Waddell, Christopher P. Barnett, Matthew Cook, Michael Field, David Fielding, Stephen B. Fox, Jozef Gecz, Adam Jaffe, Richard J. Leventer, Paul J. Lockhart, Sebastian Lunke, Andrew J. Mallett, Julie McGaughran, Linda Mileshkin, Katia Nones, Tony Roscioli, Ingrid E. Scheffer, Christopher Semsarian, Cas Simons, David M. Thomas, David R. Thorburn, Richard Tothill, Deborah White, Sally Dunwoodie, Peter T. Simpson, Peta Phillips, Marie-Jo Brion, Keri Finlay, Michael CJ. Quinn, Tessa Mattiske, Emma Tudini, Kirsten Boggs, Sean Murray, Kathy Wells, John Cannings, Andrew H. Sinclair, John Christodoulou, Kathryn N. North
Summary: Australian Genomics is a national collaborative partnership that aims to integrate genomics into healthcare through a whole-of-system approach. It has evaluated genomic testing outcomes in over 5,200 individuals across rare disease and cancer studies and provided evidence-based changes in policy and practice, resulting in government funding and access to genomic tests. It has also developed national skills, infrastructure, policy, and data resources to support data sharing and improve clinical genomic delivery.
AMERICAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Public, Environmental & Occupational Health
Camelia Harrison, Nicci Bartley, Chris Jacobs, Megan Best, Sabina Vatter, Bettina Meiser, Mandy L. Ballinger, David M. Thomas, Phyllis Butow
Summary: This study aimed to explore cancer patients' perceived importance of disclosure, predictors of perceptions, and perspectives on family communication of germline genome sequencing results. The results showed that most participants intended to disclose results to their nuclear family, considered the results as family information, and believed it was important to disclose results to family members. Education level and the level of communication within the nuclear and extended family were significantly positively associated with the perceived importance of disclosure. Low health literacy and family conflict can complicate the communication of germline genome sequencing results.
PATIENT EDUCATION AND COUNSELING
(2023)
Article
Health Care Sciences & Services
Don Husereau, Lotte Steuten, Vivek Muthu, David M. Thomas, Daryl S. Spinner, Craig Ivany, Michael Mengel, Brandon Sheffield, Stephen Yip, Philip Jacobs, Terrence Sullivan
Summary: This article synthesizes good practices for genetic/genomic testing services through a literature review, key informant interviews, and expert discussion. It identifies necessary conditions and good practices, including creating communities of practice and healthcare system networks, resource planning, and across-region informatics.
Meeting Abstract
Oncology
Danie Serie, Chad Pickering, Rachel Rice, Maurice Wong, Hector Huang, Maya Kansara, Subotheni Thavaneswaran, Mandy L. Ballinger, Lucille Sebastian, David Morgan Thomas, Klaus Lindpaintner
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Meeting Abstract
Oncology
Frank Po-Yen Lin, Subotheni Thavaneswaran, John P. Grady, Christine E. Napier, Maya Kansara, Lucille Sebastian, Damien Kee, Samantha R. Oakes, James Blackburn, Hamish S. Scott, Anthony Glover, Stephen B. Fox, David Goldstein, Paul Leo, Benhur Amanuel, Jayesh Desai, Chee Khoon Lee, Mandy L. Ballinger, John Simes, David Morgan Thomas
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Meeting Abstract
Oncology
David M. Thomas