CD45.1/CD45.2 Congenic Markers Induce a Selective Bias for CD8+ T Cells during Adoptive Lymphocyte Reconstitution in Lymphocytopenia Mice.

CD45.1/CD45.2 congenic markers have been used to track hematopoietic lineage differentiation following hematopoietic stem and progenitor cell (HSPC) transplantation.

Engineering metabolism to modulate immunity.

Metabolic programming and reprogramming have emerged as pivotal mechanisms for altering immune cell function. Thus, immunometabolism has become an attractive target area for treatment of immune-mediated disorders. Nonetheless, many hurdles to delivering metabolic cues persist.

Pembrolizumab versus methotrexate, docetaxel, or cetuximab in recurrent or metastatic head and neck squamous cell carcinoma (KEYNOTE-040): Subgroup analysis by pattern of disease recurrence.

Background: In the phase 3 KEYNOTE-040 study, pembrolizumab prolonged OS versus chemotherapy in previously treated recurrent or metastatic (R/M) HNSCC. We present a post hoc subgroup analysis by disease recurrence pattern: recurrent-only, recurrent and metastatic (recurrent-metastatic), and metastatic-only HNSCC.

Materials And Methods: Patients had HNSCC that progressed during or after platinum-containing treatment for R/M disease or had recurrence or progression within 3-6 months of previous platinum-containing definitive therapy for locally advanced disease.

Treatment strategies for malignant pulmonary nodule: beyond lobectomy. Point-counterpoint.

Purpose Of Review: Technological advancement in low-dose computed tomography resulted in an increased incidental discovery of early-stage lung cancer and multifocal ground glass opacity. The demand for parenchyma-preserving treatment strategies is greater now than ever. Pulmonary ablative therapy is a groundbreaking technique to offer local ablative treatment in a lung-sparing manner.

Novel lipid antigens for NKT cells in cancer.

Cancer immunotherapy aims to unleash the power of the immune system against tumors without the side effects of traditional chemotherapy. Immunotherapeutic methods vary widely, but all follow the same basic principle: overcome the barriers utilized by cancers to avoid immune destruction. These approaches often revolve around classical T cells, such as with CAR T cells and neoantigen vaccines; however, the utility of the innate-like iNKT cell in cancer immunotherapy has gained significant recognition.

Generative Adversarial Networks in Digital Histopathology: Current Applications, Limitations, Ethical Considerations, and Future Directions.

Generative adversarial networks (GANs) have gained significant attention in the field of image synthesis, particularly in computer vision. GANs consist of a generative model and a discriminative model trained in an adversarial setting to generate realistic and novel data. In the context of image synthesis, the generator produces synthetic images, whereas the discriminator determines their authenticity by comparing them with real examples.

Size-Specific Modulation of a Multienzyme Glucosome Assembly during the Cell Cycle.

Enzymes in glucose metabolism have been subjected to numerous studies, revealing the importance of their biological roles during the cell cycle. However, due to the lack of viable experimental strategies for measuring enzymatic activities particularly in living human cells, it has been challenging to address whether their enzymatic activities and thus anticipated glucose flux are directly associated with cell cycle progression. It has remained largely elusive how human cells regulate glucose metabolism at a subcellular level to meet the metabolic demands during the cell cycle.

Defining Biological and Biochemical Functions of Noncanonical SET Domain Proteins.

Within the SET domain superfamily of lysine methyltransferases, there is a well-conserved subfamily, frequently referred to as the Set3 SET domain subfamily, which contain noncanonical SET domains carrying divergent amino acid sequences. These proteins are implicated in diverse biological processes including stress responses, cell differentiation, and development, and their disruption is linked to diseases including cancer and neurodevelopmental disorders. Interestingly, biochemical and structural analysis indicates that they do not possess catalytic methyltransferase activity.

Racial and ethnic differences in clinical outcomes among patients with multiple myeloma treated with CAR T-cell therapy.

Idecabtagene vicleucel (ide-cel) was the first chimeric antigen receptor T-cell therapy to gain US Food and Drug Administration approval for patients with relapsed/refractory multiple myeloma (RRMM). The clinical outcomes of standard of care (SOC) ide-cel in racially and ethnically diverse populations have been understudied. This study pooled data from 207 patients with RRMM (28% patients of racial and ethnic minority groups) treated with SOC ide-cel across 11 institutions to examine racial and ethnic differences in the incidence of toxicities and adverse events, response to ide-cel, and survival.

Factors associated with refractoriness or early progression after idecabtagene vicleucel in patients with relapsed/ refractory multiple myeloma: US Myeloma Immunotherapy Consortium real world experience.

While response rates and survival outcomes have been very promising for idecabtagene vicleucel (ide-cel), a proportion of patients do not respond or relapse early after this B-cell maturation antigen (BCMA) targeted chimeric antigen receptor (CAR) T-cell therapy. Understanding the characteristics of these patients is important for patient selection and development of novel strategies to improve outcomes. We evaluated factors associated with early progression (progression or death due to myeloma ≤3 months after CAR T-cell infusion) in patients treated with standard of care ide-cel at 11 US academic centers.

Immunomodulatory properties of CD38 antibodies and their effect on anticancer efficacy in multiple myeloma.

Background: CD38 has been established as an important therapeutic target for multiple myeloma (MM), for which two CD38 antibodies are currently approved-daratumumab and isatuximab. CD38 is an ectoenzyme that degrades NAD and its precursors and is involved in the production of adenosine and other metabolites.

Aim: Among the various mechanisms by which CD38 antibodies can induce MM cell death is immunomodulation, including multiple pathways for CD38-mediated T-cell activation.

Impact of Targeting Moiety Type and Protein Corona Formation on the Uptake of Fn14-Targeted Nanoparticles by Cancer Cells.

The TWEAK receptor, Fn14, is a promising candidate for active targeting of cancer nanotherapeutics to many solid tumor types, including metastatic breast and primary brain cancers. Targeting of therapeutic nanoparticles (NPs) has been accomplished using a range of targeting moieties including monoclonal antibodies and related fragments, peptides, and small molecules. Here, we investigated a full-length Fn14-specific monoclonal antibody, ITEM4, or an ITEM4-Fab fragment as a targeting moiety to guide the development of a clinical formulation.

Community-engaged basic science in an NCI-designated comprehensive cancer center: antioxidants and chemotherapeutic efficacy.

Purpose: While community engagement has been a longstanding aspect of cancer-relevant research in social and behavioral sciences, it is far less common in basic/translational/clinical research. With the National Cancer Institute's incorporation of Community Outreach and Engagement into the Cancer Center Support Grant guidelines, successful models are desirable. We report on a pilot study supported by the University of Maryland Greenebaum Comprehensive Cancer Center (UMGCCC), that used a community-engaged, data-driven process to inform a pre-clinical study of the impact of antioxidants on the efficacy of platinum-based chemotherapeutics.

The Role of Mechanical Thrombectomy for Acute Massive Pulmonary Embolism in a Patient With Unilateral Lung Transplant and Atrial Septal Defect.

Purpose: The risk of thromboembolic disease is high in patients with lung transplantation and is associated with significant morbidity and mortality with single healthy transplanted lung. We present a case involving successful endovascular management of life-threatening acute massive pulmonary embolism (PE) in a patient with single lung transplant and atrial septal defect (ASD).

Case Report: A 65-year-old man with a history of interstitial lung disease status post single left orthotopic lung transplant in 2012 presented with acute massive PE and clot burden in the pulmonary arteries of the transplanted left lung.

Detection of extracranial and intracranial calcified carotid artery atheromas in cone beam computed tomography using a deep learning convolutional neural network image segmentation approach.

Objective: We leveraged an artificial intelligence deep-learning convolutional neural network (DL CNN) to detect calcified carotid artery atheromas (CCAAs) on cone beam computed tomography (CBCT) images.

Study Design: We obtained 137 full-volume CBCT scans with previously diagnosed CCAAs. The DL model was trained on 170 single axial CBCT slices, 90 with extracranial CCAAs and 80 with intracranial CCAAs.

VNLG-152R and its deuterated analogs potently inhibit/repress triple/quadruple negative breast cancer of diverse racial origins and by upregulating E3 Ligase Synoviolin 1 (SYVN1) and inducing proteasomal degradation of MNK1/2.

Triple-negative breast cancer (TNBC) and its recently identified subtype, quadruple negative breast cancer (QNBC), collectively account for approximately 13% of reported breast cancer cases in the United States. These aggressive forms of breast cancer are associated with poor prognoses, limited treatment options, and lower overall survival rates. In previous studies, our research demonstrated that VNLG-152R exhibits inhibitory effects on TNBC cells both and and the deuterated analogs were more potent inhibitors of TNBC cells Building upon these findings, our current study delves into the molecular mechanisms underlying this inhibitory action.

A Rapid-Patterning 3D Vessel-on-Chip for Imaging and Quantitatively Analyzing Cell-Cell Junction Phenotypes.

The blood-brain barrier (BBB) is a dynamic interface that regulates the molecular exchanges between the brain and peripheral blood. The permeability of the BBB is primarily regulated by the junction proteins on the brain endothelial cells. In vitro BBB models have shown great potential for the investigation of the mechanisms of physiological function, pathologies, and drug delivery in the brain.

Associations between social isolation and diet quality among US adults with disability participating in the National Health and Nutrition Examination Survey, 2013-2018.

Social isolation and disability are established risk factors for poor nutrition. We aimed to assess whether social isolation is associated with diet quality specifically among adults with disabilities. This cross-sectional analysis used data from the National Health and Nutrition Examination Survey, 2013-2018.

Histone Demethylase KDM3 (JMJD1) in Transcriptional Regulation and Cancer Progression.

Methylation of histone H3 lysine 9 (H3K9) is a repressive histone mark and associated with inhibition of gene expression. KDM3 is a subfamily of the JmjC histone demethylases. It specifically removes the mono- or di-methyl marks from H3K9 and thus contributes to activation of gene expression.

Immuno-oncologic signature of malignant transformation in oral squamous cell carcinoma.

Objective: The purpose of this study is to identify the immuno-oncologic (IO) signature at the surgical tumor margin (TM) of oral squamous cell carcinoma (OSCC) that is involved in the process of malignant transformation.

Study Design: Under institutional review board approval, TM of 73 OSCC were investigated using immunohistochemistry for the immune biomarker, programmed death ligand-1 (PD-L1). NanoString 770 IO-focused gene set was analyzed in 5 pairs of TM and invasive tumor (T).

Matriptase drives dissemination of ovarian cancer spheroids by a PAR-2/PI3K/Akt/MMP9 signaling axis.

The transmembrane serine protease matriptase is a key regulator of both barrier-disruptive and protective epithelial cell-cell interactions. Elevated matriptase is a consistent feature of epithelial ovarian cancers (OvCa), where multicellular spheroids shed from the primary tumor into the peritoneal cavity are critical drivers of metastasis. Dynamic cell-to-cell adhesive contacts are required for spheroid formation and maintenance.

The role of bone marrow microenvironment (BMM) cells in acute myeloid leukemia (AML) progression: immune checkpoints, metabolic checkpoints, and signaling pathways.

Acute myeloid leukemia (AML) comprises a multifarious and heterogeneous array of illnesses characterized by the anomalous proliferation of myeloid cells in the bone marrow microenvironment (BMM). The BMM plays a pivotal role in promoting AML progression, angiogenesis, and metastasis. The immune checkpoints (ICs) and metabolic processes are the key players in this process.

Idecabtagene vicleucel chimeric antigen receptor T-cell therapy for relapsed/refractory multiple myeloma with renal impairment.

We evaluated patients with relapsed multiple myeloma with renal impairment (RI) treated with standard of care idecabtagene vicleucel (ide-cel), as outcomes with chimeric antigen receptor (CAR) T-cell therapy are unknown in this population. RI was defined as creatinine clearance (CrCl) <50 mL/min. CrCl of <30 mL/min or dialysis dependence were defined as severe RI.