A5042554471- Chronic Lymphocytic Leukemia Research
- Lymphoma Diagnosis and Treatment
- Immunodeficiency and Autoimmune Disorders
- Clostridium difficile and Clostridium perfringens research
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Chronic Myeloid Leukemia Treatments
- Peptidase Inhibition and Analysis
- Microscopic Colitis
- Galectins and Cancer Biology
- Gastrointestinal Tumor Research and Treatment
- Immune Cell Function and Interaction
- Veterinary medicine and infectious diseases
- Protein Kinase Regulation and GTPase Signaling
- Cellular transport and secretion
- Animal Nutrition and Physiology
- Monoclonal and Polyclonal Antibodies Research
- Calcium signaling and nucleotide metabolism
- Cancer Mechanisms and Therapy
- Neuroendocrine Tumor Research Advances
- Viral gastroenteritis research and epidemiology
- Gut microbiota and health
- Genetics and Neurodevelopmental Disorders
- Animal Behavior and Welfare Studies
- Hip disorders and treatments
- Alzheimer's disease research and treatments
Agency for Science, Technology and Research
2024
Institute of Molecular and Cell Biology
2024
Dana-Farber Cancer Institute
2017-2020
Demos
2018
Harvard University
2017-2018
Boston University
2014-2017
Boston Medical Center
2017
Amyloidosis Foundation
2014-2017
University of Guelph
2012-2013
Purpose Ibrutinib is active in previously treated Waldenström macroglobulinemia (WM). MYD88 mutations ( MYD88MUT) and CXCR4 CXCR4MUT) affect ibrutinib response. We report on a prospective study of monotherapy symptomatic, untreated patients with WM, the effect CXCR4MUT status outcome. Patients Methods Symptomatic, treatment-naïve WM were eligible. (420 mg) was administered daily until progression or unacceptable toxicity. All tumors genotyped for MYD88MUT CXCR4MUT. Results A total 30...
Summary MYD 88 mutations are present in 95% of Waldenstrom Macroglobulinaemia ( WM ) patients, and support diagnostic discrimination from other IgM‐secreting B‐cell malignancies. Diagnostic can be difficult among suspected wild‐type WT cases. We systematically reviewed the clinical, pathological laboratory studies for 64 patients. World Health Organization consensus guidelines were used to establish clinicopathological diagnosis. Up 30% cases had an alternative diagnosis, including IgM...
Summary Ibrutinib is associated with response rate of 90% and median progression‐free survival (PFS) in excess 5 years Waldenström macroglobulinaemia (WM) patients. CXCR4 mutations are detected 30–40% patients WM associate lower rates shorter PFS to ibrutinib therapy. Both frameshift ( FS ) nonsense NS have been described. The impact these on outcomes not evaluated We studied consecutive a diagnosis WM, therapy, for the presence differences between groups. Of 180 patients, 68 (38%) had...
Transthyretin-associated forms of cardiac amyloidosis are fatal protein misfolding diseases that can be inherited (ATTRm) or acquired (ATTRwt). An accurate diagnosis ATTR challenging as biopsy evidence, usually from the affected organ, is required. Precise biomarkers for disease identification and monitoring undiscovered, disease-specific therapeutic options needed, current understanding molecular pathogenesis limited. The aim this study was to investigate compare serum proteomes in ATTRm...
Transthyretin cardiac amyloidosis (ATTR) is an underrecognized cause of heart failure (HF) in older individuals, owing part to difficulty diagnosis. ATTR can result from substitution valine for isoleucine at codon 122 the transthyretin (TTR) gene (V122I), present 3.43% African American individuals.To examine whether serum retinol-binding protein 4 (RBP4), endogenous TTR ligand, could be used as a diagnostic test V122I amyloidosis.In this combined prospective and retrospective cohort study...
There is poor understanding of most aspects Clostridium perfringens type A as a possible cause neonatal diarrhea in piglets, and the prevalence types C. present on Ontario swine farms unknown. To study fecal selected toxin genes, 48 were visited between August 2010 May 2011, 354 samples collected from suckling pigs, lactating sows, weanling grower-finisher gestating well manure pits. The cultured quantitatively, genes detected by real-time multiplex polymerase chain reaction (PCR).In mixed...
Summary Little is known about TP 53 mutations in Waldenström Macroglobulinaemia ( WM ). We evaluated 265 patients for by next‐generation sequencing, and validated the findings Sanger sequencing. were identified 6 (2·6%) that impacted DNA ‐binding domain. All six MYD 88‐ CXCR 4 ‐mutated. Ibrutinib showed activity carrying all three mutations. With a median follow‐up of 18 months, 2 (33%) with biallelic inactivation died progressive disease. are rare , associate 88 show response to ibrutinib.
Abstract Activating MYD88 mutations promote pro-survival signaling through BTK and HCK, both targets of ibrutinib. Despite high response rates, complete responses to ibrutinib are lacking, other triggered pathways may contribute primary drug resistance. B-cell receptor (BCR) has been observed in lymphomas driven by mutated MYD88, even without activating the BCR pathway mutations. We identified activated SYK (p-SYK), a component complex with -mutated WM ABC DLBCL lymphoma cells. Confocal...
Key Points CXCR4 S338X clonality ≥25% is associated with lower very good partial response and shorter progression-free survival to ibrutinib. assessment represents a novel biomarker predict outcomes ibrutinib in Waldenström macroglobulinemia patients.
Summary Ibrutinib is highly active in Waldenström macroglobulinaemia (WM) patients, but disease progression can occur due to acquired mutations BTK, the target of ibrutinib, or PLCG2, protein downstream BTK. However, not all resistant patients harbour these alterations. We have performed a whole‐exome sequencing study identify alternative molecular mechanisms that drive ibrutinib resistance. Our findings include deletions on chromosomes 6q, including homozygous deletions, and 8p, which...
Hematopoietic cell kinase (HCK) is an SRC family member that aberrantly upregulated in B-cell neoplasms dependent on MYD88-activating mutations and supports their growth survival. We showed herein activation of Toll-like receptor (TLR) signaling MYD88 wild-type B cells also triggered HCK expression, denoting path regulatory function for by MYD88. To clarify the cascades responsible aberrant expression MYD88-mutated lymphomas, we performed promoter-binding transcription factor (TF) profiling,...
"Retinol binding protein 4 (RBP4) concentration identifies V122I transthyretin cardiac amyloidosis." Amyloid, 24(sup1), pp. 120–121
This review presents a framework for assessing the efficacy of antimicrobials used to control necrotic enteritis (NE) caused byClostridium perfringens (CP) in context susceptibility testing and clinical efficacy, their potential interactions with intestinal microbiota poultry. Practitioners have traditionally based choice antimicrobial agent on testing, but there appears be lack correlation in-feed (particularly bacitracin virginiamycin). Resistance patterns CP been monitored using...
Two new monoclonal antibodies, one a mouse IgM and the other human that reacted with guanosine, were compared to serum antibodies from patients systemic lupus erythematosus (SLE). The antibody was polyspecific in its binding nucleoside bases, whereas relatively specific for guanosine when by using an enzyme-linked immunosorbent assay (ELISA). Neither bound polyguanylic acid or denatured single-stranded (ss) DNA, however. Serum IgG seven SLE cross-reacted showed considerable specificity...
Rituximab-containing regimens are commonly used for frontline therapy in patients with symptomatic Waldenström macroglobulinemia (WM). We had observed that a portion of WM experienced deepening response months to years after completion. carried retrospective study aimed at describing this phenomenon. gathered baseline data, and responses end induction, maintenance best response. Deepening was defined as ≥25% decrease serum IgM achieved later time from Of 178 included, 116 (65%) received 62...