A5005940775- Pomegranate: compositions and health benefits
- Cancer Research and Treatments
- Acute Myeloid Leukemia Research
- Multiple Myeloma Research and Treatments
- Bioactive Compounds in Plants
- Herpesvirus Infections and Treatments
- Virus-based gene therapy research
- Protein Degradation and Inhibitors
- Nuclear Structure and Function
- Chronic Lymphocytic Leukemia Research
- RNA Research and Splicing
- interferon and immune responses
- Garlic and Onion Studies
- Chronic Myeloid Leukemia Treatments
- Pancreatitis Pathology and Treatment
- Cancer Genomics and Diagnostics
- HIV/AIDS drug development and treatment
- Radiomics and Machine Learning in Medical Imaging
- Pancreatic and Hepatic Oncology Research
- Genetic factors in colorectal cancer
- Animal Virus Infections Studies
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Lymphoma Diagnosis and Treatment
- Phagocytosis and Immune Regulation
- Cynara cardunculus studies
University of Miami
2018-2024
Sylvester Comprehensive Cancer Center
2018-2024
Covalent (irreversible) Bruton's tyrosine kinase (BTK) inhibitors have transformed the treatment of multiple B-cell cancers, especially chronic lymphocytic leukemia (CLL). However, resistance can arise through mechanisms, including acquired mutations in BTK at residue C481, binding site covalent inhibitors. Noncovalent (reversible) overcome this mechanism and other sources resistance, but mechanisms to these therapies are currently not well understood.
Increasing use of covalent and noncovalent inhibitors Bruton's tyrosine kinase (BTK) has elucidated a series acquired drug-resistant BTK mutations in patients with B cell malignancies. Here we identify inhibitor resistance distinct enzymatic activities, including some that impair activity while imparting novel protein-protein interactions sustain receptor (BCR) signaling. Furthermore, describe clinical-stage IKZF1/3 degrader, NX-2127, can bind proteasomally degrade each mutant proteoform,...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy and highly resistant to standard treatment regimens. Targeted therapies against KRAS, a mutation present in overwhelming majority of PDAC cases, have been largely ineffective. However, inhibition downstream components the KRAS signaling cascade provides promising therapeutic targets management warrants further exploration. Here, we investigated Urolithin A (Uro A), novel natural compound derived from pomegranates,...
PurposeThe gold nanoparticle (GNP) as a promising theranostic probe has been increasingly studied. The tumor-targeting efficiency of GNPs is crucial to increase the therapeutic ratio. In this study, we developed PSMA-targeted enhance GNP uptake in prostate cancer and an x-ray fluorescence imaging system noninvasively monitor assess delivery.Methods MaterialsFor targeted therapy cancer, anti–prostate-specific membrane antigen (PSMA) antibodies were conjugated onto PEGylated through...
Although smoking is a significant risk factor for pancreatic ductal adenocarcinoma (PDAC), the molecular mechanisms underlying PDAC development and progression in smokers are still unclear. Here, we show role of cyclic AMP response element-binding protein (CREB) pathogenesis smoking-induced PDAC. Smokers had significantly higher levels activated CREB when compared with nonsmokers. Cell lines derived from normal pancreas intraepithelial neoplasm (PanIN) exhibited low baseline pCREB cell...
XPO1 (Exportin-1) is the nuclear export protein responsible for normal shuttling of several proteins and RNA species between nucleocytoplasmic compartment eukaryotic cells. recognizes signal (NES) its cargo to facilitate export. Alterations have been shown play a role in oncogenesis types solid tumour haematologic cancers. Over more than decade, there has substantial progress targeting cancer using selective inhibitors. This resulted recent approval first-in-class drug selinexor use...
Patients with multiple myeloma-bearing translocation t(11;14) have recently been shown to benefit from the apoptosis-inducing drug venetoclax; however, lacks FDA approval in myeloma thus far due a potential safety signal overall patient population. Selinexor is an inhibitor of nuclear export that FDA-approved for patients refractory lines therapy. Here, we report four t(11;14), concomitant administration venetoclax and selinexor was safe associated disease response. Moreover, combination...
Heavy alcohol consumption is the dominant risk factor for chronic pancreatitis (CP); however, treatment and prevention strategies alcoholic (ACP) remains limited. The present study demonstrates that ACP induction in C57BL/6 mice causes significant acinar cell injury, pancreatic stellate (PSC) activation, exocrine function insufficiency, an increased fibroinflammatory response when compared with or CP alone. Although withdrawal of during recovery led to reversion damage, continued established...
Vesicular stomatitis virus (VSV) expressing IFNβ induces apoptosis in multiple tumor models while maintaining an excellent safety profile. VSV-IFNβ is oncoselective due to permissive replication cells with altered IFN pathway. The human (hIFNβ) vector currently used clinical trials as a standalone therapy; however, we hypothesized that oncolytic virotherapy might be more effective when combination radiotherapy (RT). We investigated the synergistic effects of RT and VSV-hIFNβ subcutaneous PC3...
An important epigenetic component of tyrosine kinase signaling is the phosphorylation histones, and readers, writers, erasers. Phosphorylation protein arginine methyltransferases (PRMTs), have been shown to enhance impair their enzymatic activity. In this study, we show that hyperactivation Janus 2 (JAK2) by V617F mutation phosphorylates residues (Y149 Y334) in coactivator-associated methyltransferase 1 (CARM1), an target hematologic malignancies, increasing its activity altering...
STK17A is a novel uncharacterized member of the death-associated protein family serine and threonine kinases. Overexpression observed in many cancers. We identified lead compound that based on quinazoline core. Optimizations led to discovery potent selective STK17A/B inhibitors with drug-like properties oral bioavailability. Compound 9 had an inhibitory IC50 23 nM. Based profiling studies against two wild-type kinase panels (375 398 kinases, respectively), strong inhibition both STK17B but...
SF3B1 mutations frequently occur in cancer yet lack targeted therapies. Clinical trials of XPO1 inhibitors, selinexor and eltanexor, high-risk myelodysplastic neoplasms (MDS) revealed responders were enriched with mutations. Given that (Exportin-1) is a nuclear exporter responsible for the export proteins multiple RNA species, this led to hypothesis SF3B1-mutant cells are sensitive inhibition, potentially due altered splicing. Subsequent sequencing after inhibition wildtype mutant showed...
Purpose Immunotherapy (IT) and radiotherapy (RT) can act synergistically, enhancing antitumor response beyond what either treatment achieve separately. Anecdotal reports suggest that these results are in part due to the induction of an abscopal effect on non-irradiated lesions. Systematic data incidence scarce, while existence identification predictive signatures or this phenomenon lacking. The purpose pre-clinical investigational work is shed more light subject by identifying several...
Combined radiotherapy (RT) and immune checkpoint-inhibitor (ICI) therapy can act synergistically to enhance tumor response beyond what either treatment achieve alone. Alongside the revolutionary impact of ICIs on cancer therapy, life-threatening potential side effects, such as checkpoint-inhibitor-induced (CIP) pneumonitis, remain underreported unpredictable. In this preclinical study, we hypothesized that routinely collected data imaging, blood counts, cytokine levels be utilized build a...
Triple-negative breast cancer (TNBC), which is a type of invasive cancer, characterized by severe disease progression, poor prognosis, high recurrence rate, and short survival. We sought to gain new insight into TNBC applying computed tomography (CT) magnetic resonance (MR) quantitative imaging (radiomics) approaches predict the outcome radio-immunotherapy treatments in syngeneic subcutaneous murine tumor model. Five Athymic Nude mice were implanted with cell lines (4T1) tumors on right...
Abstract BACKGROUND AND AIMS In vivo induction of alcoholic chronic pancreatitis (ACP) causes significant acinar damage, increased fibroinflammatory response, and heightened activation cyclic response element binding protein 1 (CREB) when compared with alcohol (A) or (CP) mediated pancreatic damage. However, the study elucidating cooperative interaction between CREB oncogenic Kras G12D/+ ( Kras* ) in promoting cancer progression ACP remains unexplored. METHODS Experimental was established...
Abstract Background: Acute myeloid leukemia (AML) with KMT2A-rearrangements have a poor prognosis and so there is an urgent need for novel therapies. Menin inhibitors shown promising anti-leukemic effects in KMT2A-rearranged NPM1-mutated AML. However, the efficacy of menin as single agents may be limited by development resistance mutations. Combining other epigenetic drugs present strategy to enhance their therapeutic potential. In this study, we performed combination drug screen using...