245 results match your criteria: "University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center[Affiliation]"

Our previous studies have demonstrated that pegcrisantaspase (PegC), a long-acting asparaginase, synergizes with the BCL-2 inhibitor Venetoclax (Ven) in vitro and in vivo; however, the anti-leukemic activity of -derived asparaginases in combination with BCL-2 inhibition, and potential synergy with inhibitors of MCL-1, a key resistance factor of BCL-2 inhibition, has yet to be determined. Using a combination of human AML cells lines, primary samples, and in vivo xenograft mouse models, we established the anti-leukemic activity of the BCL-2 inhibitor S55746 and the MCL-1 inhibitor S63845, alone and in combination with the long-acting asparaginase calaspargase pegol-mknl (CalPegA). We report that CalPegA enhances the anti-leukemic effect of S55746 but does not impact the activity of S63845.

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Mast cells proliferate in the peri-hippocampal space during early development and modulate local and peripheral immune cells.

Dev Cell

November 2024

Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA; University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA; Medicine Institute for Neuroscience Discovery, University of Maryland, Baltimore, MD 21201, USA. Electronic address:

Brain development is a non-linear process of regionally specific epochs occurring during windows of sensitivity to endogenous and exogenous stimuli. We have identified an epoch in the neonatal rat brain defined by a transient population of peri-hippocampal mast cells (phMCs) that are abundant from birth through 2-weeks post-natal but absent thereafter. The phMCs are maintained by proliferation and harbor a unique transcriptome compared with mast cells residing in the skin, bone marrow, or other brain regions.

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Leptomeningeal metastatic disease (LMD), encompassing entities of 'meningeal carcinomatosis', neoplastic meningitis' and 'leukaemic/lymphomatous meningitis', arises secondary to the metastatic dissemination of cancer cells from extracranial and certain intracranial malignancies into the leptomeninges and cerebrospinal fluid. The clinical burden of LMD has been increasing secondary to more sensitive diagnostics, aggressive local therapies for discrete brain metastases, and improved management of extracranial disease with targeted and immunotherapeutic agents, resulting in improved survival. However, owing to drug delivery challenges and the unique microenvironment of LMD, novel therapies against systemic disease have not yet translated into improved outcomes for these patients.

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Glioblastoma (GBM), the most common and aggressive primary central nervous system (CNS) tumor in adults, continues to have a dismal prognosis. Across hundreds of clinical trials, few novel approaches have translated to clinical practice while survival has improved by only a few months over the past three decades. Randomized controlled trials of immune checkpoint inhibitors (ICIs), which have seen impressive success for advanced or metastatic extracranial solid tumors, have so far failed to demonstrate a clinical benefit for patients with GBM.

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DNA methyltransferase and poly(ADP-ribose) polymerase inhibitors (DNMTis, PARPis) induce a stimulator of interferon (IFN) genes (STING)-dependent pathogen mimicry response (PMR) in ovarian (OC) and other cancers. We now show that combining DNMTis and PARPis upregulates expression of a little-studied nucleic-acid sensor, NFX1-type zinc finger-containing 1 protein (ZNFX1). We demonstrate that ZNFX1 is a novel master regulator for PMR induction in mitochondria, serving as a gateway for STING-dependent PMR.

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Sumoylation of thymine DNA glycosylase impairs productive binding to substrate sites in DNA.

J Biol Chem

November 2024

Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland, USA; Molecular and Structural Biology Program, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, Maryland, USA. Electronic address:

Article Synopsis
  • The enzyme thymine DNA glycosylase (TDG) plays a crucial role in correcting DNA mistakes and removing methyl groups from DNA, but its activity is reduced when modified by SUMO (small ubiquitin-like modifier).
  • Research using kinetic experiments indicated that SUMOylation lowers TDG's ability to properly bind and repair various DNA mispairs, ultimately decreasing its effectiveness.
  • A specific mutation in TDG’s SUMO interaction site can restore its glycosylase activity by improving its ability to bind to damaged DNA, suggesting that intramolecular interactions between SUMO and TDG can negatively impact its function.
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Outer mitochondrial membrane E3 Ub ligase MARCH5 controls de novo peroxisome biogenesis.

Dev Cell

October 2024

Center for Biomedical Engineering and Technology, University Hospital Basel, University of Basel, Basel, Switzerland; Department of Biochemistry and Molecular Biology, University Hospital Basel, University of Basel, Basel, Switzerland; Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. Electronic address:

We report that the outer mitochondrial membrane (OMM)-associated E3 Ub ligase MARCH5 is vital for generating mitochondria-derived pre-peroxisomes. In human immortalized cells, MARCH5 knockout leads to the accumulation of immature peroxisomes, reduced fatty-acid-induced peroxisomal biogenesis, and abnormal peroxisome biogenesis in MARCH5/Pex14 and MARCH5/Pex3 dko cells. Upon fatty-acid-induced peroxisomal biogenesis, MARCH5 redistributes to peroxisomes, and ubiquitination activity-deficient mutants of MARCH5 accumulate on peroxisomes containing high levels of the OMM protein Tom20 (mitochondria-derived pre-peroxisomes).

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Article Synopsis
  • * Innate lymphocytes, particularly NK cells and MAIT cells, play a crucial role in protecting against Typhi infection through IFN-γ production and their interaction with intestinal epithelial cells (EC), which influences immune responses.
  • * This study reveals that the absence of EC in cultures leads to increased IFN-γ expression in NK and MAIT cells, along with specific epigenetic changes, highlighting the complex relationship between intestinal cells and immune regulation during Typhi infection.
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Disparities in child protective services involvement in pediatric traumatic brain injury.

Pediatr Surg Int

September 2024

Department of Surgery, Stony Brook Medicine, Stony Brook, NY, 11794, USA.

Purpose: Traumatic brain injury (TBI) is a leading cause of pediatric death and disability. Abusive head trauma confers greater morbidity and mortality compared with accidental TBI. National trends reveal disproportionate involvement of minority children in the child welfare system.

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TCR3d 2.0: expanding the T cell receptor structure database with new structures, tools and interactions.

Nucleic Acids Res

September 2024

Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.

Recognition of antigens by T cell receptors (TCRs) is a key component of adaptive immunity. Understanding the structures of these TCR interactions provides major insights into immune protection and diseases, and enables design of therapeutics, vaccines and predictive modeling algorithms. Previously, we released TCR3d, a database and resource for structures of TCRs and their recognition.

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Article Synopsis
  • The study investigates the role of circulating T follicular helper cells (cT) in the immune response to Typhi infection, using data from a controlled human infection model.
  • Participants who did not develop typhoid disease (NoTD) showed higher frequencies of specific cT subsets (cT2 and cT17) compared to those who developed the disease (TD), particularly a week post-challenge.
  • The findings suggest that these cT subsets are associated with the production of anti-Typhi antibodies and could be crucial for developing effective vaccines against typhoid disease.
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The mucosal immune system is a critical first line of defense to infectious diseases, as many pathogens enter the body through mucosal surfaces, disrupting the balanced interactions between mucosal cells, secretory molecules, and microbiota in this challenging microenvironment. The mucosal immune system comprises of a complex and integrated network that includes the gut-associated lymphoid tissues (GALT). One of its primary responses to microbes is the secretion of IgA, whose role in the mucosa is vital for preventing pathogen colonization, invasion and spread.

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MR Imaging-Guided Focused Ultrasound-Clinical Applications in Managing Malignant Gliomas.

Magn Reson Imaging Clin N Am

November 2024

Department of Neurosurgery, University of Maryland School of Medicine, S-12D, 22 South Greene Street, Baltimore, MD 21201, USA; University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center. Electronic address:

Malignant gliomas (MGs) are the most common primary brain tumors in adults. Despite recent advances in understanding the biology and potential therapeutic vulnerabilities of MGs, treatment options remain limited as the delivery of drugs is often impeded by the blood-brain barrier (BBB), and safe, complete surgical resection may not always be possible, especially for deep-seated tumors. In this review, the authors highlight emerging applications for MR imaging-guided focused ultrasound (MRgFUS) as a noninvasive treatment modality for MGs.

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Importance: Racial disparities in prostate cancer are likely the result of complex relationships between both socioeconomic and environmental factors captured by the neighborhood environment and genetic factors, including West African genetic ancestry. However, few studies have examined the combined role of neighborhood environment and genetic ancestry in developing lethal prostate cancer.

Objective: To examine the interactions between West African genetic ancestry and neighborhood deprivation in modifying prostate cancer risk and mortality.

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Background: Artificial intelligence (AI)-based tools have shown promise in histopathology image analysis in improving the accuracy of oral squamous cell carcinoma (OSCC) detection with intent to reduce human error.

Objectives: This systematic review and meta-analysis evaluated deep learning (DL) models for OSCC detection on histopathology images by assessing common diagnostic performance evaluation metrics for AI-based medical image analysis studies.

Methods: Diagnostic accuracy studies that used DL models for the analysis of histopathological images of OSCC compared to the reference standard were analyzed.

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Myelofibrosis (MF) in the chronic phase is a challenging disease to treat, and conventional treatment options are geared toward symptom palliation. In this prospective, multicenter, phase 2 trial, 21 patients with MF (18 chronic phase, 2 accelerated phase, and 1 blast phase) were treated with a 10-day schedule of subcutaneous decitabine at 0.3 mg/kg per day.

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Multimodality imaging of urinary tract tuberculosis.

Abdom Radiol (NY)

August 2024

Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, 22 S. Greene St., Baltimore, MD, 21201, USA.

Imaging is a key component of diagnosis and treatment response evaluation of urinary tract tuberculosis (UT TB). Tuberculosis can have a long latency, but if found early, one may have the opportunity to prevent complications such as ureteral strictures, obstructive nephropathy, contracted (thimble) bladder, renal parenchymal destruction/calcification, and renal failure. Imaging can aid in diagnosis and differential diagnoses, evaluate the extent of disease and complications, and guide image-directed biopsy, surgical planning, and evaluation of treatment response.

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Article Synopsis
  • The 2022 European LeukemiaNet (ELN) classification predicts outcomes for younger acute myeloid leukemia (AML) patients but was tested for those aged 60 and older receiving lower-intensity treatment (LIT), involving 595 patients with varying risk levels.
  • Results showed that while ELN risk is predictive of overall survival, it fails to distinguish between favorable and intermediate risks, prompting further exploration into adverse-risk patients' molecular abnormalities.
  • A new "Beat-AML" risk classification was developed, combining favorable and intermediate risks and integrating mutation scoring, leading to better survival predictions for older AML patients and aiding treatment decisions with clear risk group delineations.
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Responsible artificial intelligence for addressing equity in oral healthcare.

Front Oral Health

July 2024

Department of Oral and Craniofacial Sciences, School of Dentistry, University of Missouri-Kansas City, Kansas City, MO, United States.

Oral diseases pose a significant burden on global healthcare. While many oral conditions are preventable and manageable through regular dental office visits, a substantial portion of the population faces obstacles in accessing essential and affordable quality oral healthcare. In this mini review, we describe the issue of inequity and bias in oral healthcare and discuss various strategies to address these challenges, with an emphasis on the application of artificial intelligence (AI).

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Introduction: The effects of antioxidant dietary supplements on response to biological therapies for cancer is unknown. We conducted a scoping review of the available systematic review evidence on this question.

Methods And Analysis: We searched six databases from inception to August 19, 2022 for systematic reviews of randomized controlled trials of antioxidant dietary supplements used by patients receiving curative chemotherapy, radiotherapy, or other biological therapy for cancer and assessing the impact of supplements on survival, treatment response, or disease progression.

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Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with a ∼50% response rate to immune checkpoint blockade (ICB) therapy. To identify predictive biomarkers, we integrated bulk and single-cell RNA sequencing (RNA-seq) with spatial transcriptomics from a cohort of 186 samples from 116 patients, including bulk RNA-seq from 14 matched pairs pre- and post-ICB. In nonresponders, tumors show evidence of increased tumor proliferation, neuronal stem cell markers, and IL1.

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Stage IA papillary and chromophobe renal cell carcinoma: effectiveness of cryoablation and partial nephrectomy.

Insights Imaging

July 2024

Division of Vascular and Interventional Radiology, Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA.

Objectives: To evaluate the effectiveness of cryoablation compared to partial nephrectomy in patients with stage IA papillary and chromophobe renal cell carcinoma (pRCC; chRCC).

Material And Methods: The 2004-2016 National Cancer Database was queried for adult patients with stage IA pRCC or chRCC treated with cryoablation or partial nephrectomy. Patients receiving systemic therapy or radiotherapy, as well as those with bilateral RCC or prior malignant disease were excluded.

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Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease without meaningful therapeutic options beyond the first salvage therapy. Targeting PDAC metabolism through amino acid restriction has emerged as a promising new strategy, with asparaginases, enzymes that deplete plasma glutamine and asparagine, reaching clinical trials. In this study, we investigated the anti-PDAC activity of the asparaginase formulation Pegcrisantaspase (PegC) alone and in combination with standard-of-care chemotherapeutics.

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A Linear Relationship between the Number of Cancers among First-Degree Relatives and the Risk of Multiple Primary Cancers.

Cancer Prev Res (Phila)

June 2024

Division of Cancer Epidemiology and Genetics, Occupational and Environmental Epidemiology Branch, National Cancer Institute, Bethesda, Maryland.

With advances in the early detection and treatment of cancer, the incidence of multiple primary cancers (MPC) or second primary cancers has increased over time. Characterization of etiologic risk factors, including family history of cancer, within the general population is critical for assessing MPC risk in patients. We examined the association between family history of cancer among first-degree relatives and MPC risk in a prospective study of 139,958 participants from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

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