Publications by authors named "Hunter Z"

Article Synopsis
  • Covalent Bruton's tyrosine kinase-inhibitors (cBTK-i) are effective in treating MYD88-mutated Waldenstrom's macroglobulinaemia by inhibiting key signaling pathways that promote tumor growth.* -
  • BTK mutations can lead to treatment resistance by reactivating ERK1/2, which causes increased inflammatory cytokine production and helps BTK wild-type tumor cells survive.* -
  • Pirtobrutinib, a non-covalent BTK-inhibitor, has been shown to successfully block damaging ERK1/2 activity and can overcome resistance in MYD88 lymphoma cells with mutated BTK.*
View Article and Find Full Text PDF

Intact executive functions are required for proper performance of cognitive tasks and relies on balance of excitatory and inhibitory (E/I) transmission in the medial prefrontal cortex (mPFC). Hypofrontality is a state of decreased activity in the mPFC and is seen in several neuropsychiatric conditions, including substance use disorders. People who chronically use methamphetamine (meth) develop hypofrontality and concurrent changes in cognitive processing across several domains.

View Article and Find Full Text PDF

Ataxia Telangiectasia (AT) is a rare disorder caused by mutations in the ATM gene and results in progressive neurodegeneration for reasons that remain poorly understood. In addition to its central role in nuclear DNA repair, ATM operates outside the nucleus to regulate metabolism, redox homeostasis and mitochondrial function. However, a systematic investigation into how and when loss of ATM affects these parameters in relevant human neuronal models of AT was lacking.

View Article and Find Full Text PDF
Article Synopsis
  • A clinical trial was conducted to investigate the effects of combining two drugs, ibrutinib and venetoclax, for treating symptomatic, treatment-naïve patients with MYD88-mutated Waldenström macroglobulinemia (WM).
  • Out of 45 patients enrolled, 42% achieved a very good partial response (VGPR), and the study noted significant adverse events, including a concerning rate of ventricular arrhythmia.
  • After a median follow-up of 24.4 months, the study reported strong progression-free survival (76%) and overall survival (96%) rates, even though it was terminated early due to safety concerns.
View Article and Find Full Text PDF
Article Synopsis
  • - Waldenström's macroglobulinemia (WM) is characterized as a type of lymphoma involving IgM monoclonal gammopathy and requires evidence of lymphoplasmacytic leukemia in the bone marrow for diagnosis.
  • - Immunophenotyping and genotyping are crucial for accurately diagnosing WM and distinguishing it from similar diseases like marginal zone lymphoma and multiple myeloma.
  • - The text emphasizes the need for standardized methodologies in mutational analysis for WM diagnosis and suggests exploring the diagnostic value of certain gene mutations that are not routinely assessed.
View Article and Find Full Text PDF

Apart from the MYD88 mutation, extensive information exists on the molecular mechanisms in Waldenström's Macroglobulinemia and its potential utility in the diagnosis and treatment tailoring. However, no consensus recommendations are yet available. Consensus Panel 3 (CP3) of the 11th International Workshop on Waldenström's Macroglobulinemia (IWWM-11) was tasked with reviewing the current molecular necessities and best way to access the minimum data required for a correct diagnosis and monitoring.

View Article and Find Full Text PDF
Article Synopsis
  • Waldenström macroglobulinemia (WM) is a rare non-Hodgkin lymphoma marked by malignant lymphoplasmacytic cells in the bone marrow, where researchers studied the tumor microenvironment using mass cytometry (CyTOF).
  • The study found a significant increase in specific B cell types and changes in immune cell populations, indicating that certain immune responses in the bone marrow are linked to better overall survival in WM patients.
  • Results showed that immune checkpoints had a role in altering the immune landscape, and the effectiveness of the drug ibrutinib was connected to the levels of immature B cells and specific T cell subsets, highlighting CyTOF as a valuable tool for understanding WM and guiding treatments.
View Article and Find Full Text PDF
Article Synopsis
  • * Researchers found that GPER1 is significantly increased in tumor cells of WM patients when compared to normal B cells.
  • * The GPER1-selective agonist G-1 (Tespria) induces cell cycle arrest and apoptosis in cancer cells, activating the TP53 pathway and showing promise for further clinical development in WM treatment.
View Article and Find Full Text PDF

Brain organoids are three-dimensional models of the developing human brain and provide a compelling, cutting-edge platform for disease modeling and large-scale genomic and drug screening. Due to the self-organizing nature of cells in brain organoids and the growing range of available protocols for their generation, issues with heterogeneity and variability between organoids have been identified. In this protocol paper, we describe a robust and replicable protocol that largely overcomes these issues and generates cortical organoids from neuroectodermal progenitors within 1 month, and that can be maintained for more than 1 year.

View Article and Find Full Text PDF
Article Synopsis
  • The HCK family kinase is upregulated and activated by mutated MYD88 in specific types of lymphomas, triggering key signaling pathways like BTK, AKT, and ERK.
  • In MYD88Mut lymphoma cells, HCK enhances SYK activation, while the SFK LYN plays a lesser role in certain lymphoma types, such as Waldenstrom macroglobulinemia.
  • Overexpression of HCK leads to persistent activation of SYK, and inhibiting HCK reduces SYK activity, indicating that HCK could be a potential therapeutic target for treating MYD88Mut B-cell lymphomas.
View Article and Find Full Text PDF

In this paper, we describe the generation and validation of human induced pluripotent stem cell (hiPSC) lines from peripheral blood mononuclear cells (PBMCs) from 6 epilepsy patients using a non-integrative Sendai virus vector. These human cellular models will enable patient-specific drug screening to improve outcomes for individuals with this disorder.

View Article and Find Full Text PDF
Article Synopsis
  • BTK inhibitors, like ibrutinib, are currently the only FDA-approved treatments for Waldenström macroglobulinemia (WM), but the factors affecting their effectiveness were not fully understood.
  • In a study of 319 WM patients on ibrutinib, CXCR4 mutations and low platelet counts were linked to worse treatment responses and shorter progression-free survival, leading to a proposed scoring system based on these factors.
  • The research found that older age (65+) greatly impacts overall survival and confirmed the significance of CXCR4 mutations as predictors for patient outcomes on ibrutinib.
View Article and Find Full Text PDF
Article Synopsis
  • BCL2 is overexpressed in Waldenström macroglobulinemia (WM) cells, and venetoclax, a BCL2 inhibitor, shows potential for causing cell death in these cases, yet its effectiveness in WM needed further investigation.
  • A phase II clinical trial demonstrated venetoclax's promising results in 32 treated patients, with overall response rates of 84%, and a median progression-free survival of 30 months.
  • The treatment was generally well-tolerated, with neutropenia as the main side effect, and the presence of certain mutations did not influence the overall treatment outcomes.
View Article and Find Full Text PDF
Article Synopsis
  • Immunoglobulin M (IgM) multiple myeloma (MM) is a rare condition that needs to be differentiated from other similar diseases, such as Waldenström macroglobulinemia, for effective treatment.
  • The study involved analyzing genomic and transcriptomic data of IgM-MM samples through whole-genome and transcriptome sequencing, revealing shared characteristics with MM, but unique features like specific chromosomal translocations and deletions.
  • Findings indicated that IgM-MM likely originates before the germinal center stage, highlighted by unique molecular signatures and elevated expression of potential therapeutic targets, such as CD20 and Bruton tyrosine kinase.
View Article and Find Full Text PDF

Epilepsy is a common neurological disorder characterized by seizures. Unfortunately, 30-40% of all epilepsy patients are resistant to at least two or more anti-seizure medications. Attempts to treat these patients and prevent further seizures necessitates multiple drug trials for the patient.

View Article and Find Full Text PDF
Article Synopsis
  • - This study evaluated the effectiveness of ibrutinib, a daily treatment for 30 patients newly diagnosed with Waldenstrom macroglobulinemia (WM), showing promising response rates: 100% overall response, 87% major response, and 30% very good partial response (VGPR) after 50 months of follow-up.
  • - Patients with CXCR4 mutations had lower VGPR rates (14% vs. 44%) and longer times to achieve major responses compared to those without mutations, indicating a possible impact of these mutations on treatment outcomes.
  • - Despite some treatment-related side effects, including fatigue and atrial fibrillation in 20% of patients, the study concluded that ibrutinib
View Article and Find Full Text PDF

Human olfactory neurosphere-derived (ONS) cells are derived from the olfactory mucosa and display some progenitor- and neuronal cell-like properties, making them useful models of neurological disorders. However, they lack several important characteristics of true neurons, which can be overcome using induced pluripotent stem cell (iPSC) -derived neurons. Here we describe, for the first time, the generation and validation of an iPSC line from an olfactory biopsy from a control cohort member.

View Article and Find Full Text PDF

Ataxia Telangiectasia is a rare autosomal recessive disorder caused by a mutated ATM gene. The most debilitating symptom of Ataxia Telangiectasia is the progressive neurodegeneration of the cerebellum, though the molecular mechanisms driving this degeneration remains unclear. Here we describe the generation and validation of an induced pluripotent stem cell (iPSC) line from an olfactory biopsy from a patient with Ataxia Telangiectasia.

View Article and Find Full Text PDF
Article Synopsis
  • Multiple sclerosis is an autoimmune disease that damages the central nervous system, leading to inflammation and nerve damage.
  • Recent advancements in treatments and understanding of the disease have improved how it progresses and affects patients' lives.
  • The latest recommendations from the Multiple Sclerosis Therapy Consensus Group focus on disease-modifying therapies, specifically for regions in Europe, based on the most current scientific evidence.
View Article and Find Full Text PDF
Article Synopsis
  • MYD88 and CXCR4 mutations are frequently found in Waldenström macroglobulinemia (WM) and the CXCR4 mutation can affect patient response to BTK inhibitors.
  • A phase 1 trial tested the CXCR4-antagonist ulocuplumab combined with ibrutinib, enrolling 13 symptomatic patients, which resulted in significant declines in median immunoglobulin M levels and bone marrow disease.
  • The study achieved high response rates, with a 2-year progression-free survival of 90%, while showing that combining the two treatments is feasible and well-tolerated, despite some adverse events.
View Article and Find Full Text PDF

Ibrutinib is highly active and produces long-term responses in patients with Waldenström macroglobulinemia (WM), but acquired resistance can occur with prolonged treatment. We therefore evaluated the natural history and treatment outcomes in 51 WM patients with acquired resistance to ibrutinib monotherapy. The median time between ibrutinib initiation and discontinuation was 2 years (range, 0.

View Article and Find Full Text PDF