Publications by authors named "Benjamin J Dipardo"

Background: Pancreatic neuroendocrine tumors (pNETs) are genomically diverse tumors. The management of newly diagnosed well-differentiated pNETs is limited by a lack of sensitivity of existing biomarkers for prognostication. Our goal was to investigate the potential utility of genetic markers as a predictor of progression-free survival (PFS) and recurrence-free survival (RFS).

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Ionizing radiation (IR) can reprogram proteasome structure and function in cells and tissues. In this article, we show that IR can promote immunoproteasome synthesis with important implications for Ag processing and presentation and tumor immunity. Irradiation of a murine fibrosarcoma (FSA) induced dose-dependent de novo biosynthesis of the immunoproteasome subunits LMP7, LMP2, and Mecl-1, in concert with other changes in the Ag-presentation machinery (APM) essential for CD8+ T cell-mediated immunity, including enhanced expression of MHC class I (MHC-I), β2-microglobulin, transporters associated with Ag processing molecules, and their key transcriptional activator NOD-like receptor family CARD domain containing 5.

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Article Synopsis
  • Cytosolic DNA in unstable metastatic cancer cells activates the cGAS-STING immune pathway, but tumors can evade immune detection by manipulating inflammatory signals.
  • The enzyme ENPP1 plays a key role in promoting metastasis by breaking down cGAMP, which normally stimulates immune responses, leading to the production of adenosine that suppresses immunity.
  • Loss of ENPP1 reduces metastasis and enhances the effectiveness of immunotherapy by allowing more immune cells to infiltrate tumors, while high levels of ENPP1 are linked to increased metastasis and resistance to treatments like anti-PD-1/PD-L1.
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The use of upfront chemotherapy for primary localized soft tissue sarcoma (STS) of the extremity and trunk is debated. It remains unclear if chemotherapy adds clinical benefit, which patients are likely to benefit, and whether the timing of therapy affects outcomes. We used the National Cancer Database (NCDB) to examine the association between overall survival (OS) and chemotherapy in 5436 patients with the five most common subtypes of STS with primary disease localized to the extremity or trunk, mirroring the patient population of a modern phase 3 clinical trial of neoadjuvant chemotherapy.

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  • The study examined chemotherapy usage patterns in adult patients with high-grade soft tissue sarcoma (STS) in the U.S., noting a low overall chemotherapy usage rate of 22%.
  • Among patients receiving chemotherapy, a significant majority (85%) were treated with multiagent therapies, while nearly half (47%) underwent neoadjuvant chemotherapy prior to surgery.
  • Factors influencing chemotherapy use included tumor characteristics, patient demographics, income levels, and treatment facility types, but no significant change in chemotherapy usage trends was observed over the study period (2004-2016).
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Somatic copy number alterations (SCNAs) are important genetic drivers of many cancers. We investigated the feasibility of obtaining SCNA profiles from circulating tumor cells (CTCs) as a molecular liquid biopsy for hepatocellular carcinoma (HCC). CTCs from ten HCC patients underwent SCNA profiling.

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Cancer is one of the leading causes of death worldwide, despite the large efforts to improve the understanding of cancer biology and development of treatments. The attempts to improve cancer treatment are limited by the complexity of the local milieu in which cancer cells exist. The tumor microenvironment (TME) consists of a diverse population of tumor cells and stromal cells with immune constituents, microvasculature, extracellular matrix components, and gradients of oxygen, nutrients, and growth factors.

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Background: Malignant peripheral nerve sheath tumors (MPNSTs) comprise a rare, aggressive subtype of soft tissue sarcoma. While surgery is the mainstay of therapy for this disease, the role of neoadjuvant therapy remains undefined.

Methods: This study reviewed patients 16 years of age and older who underwent surgical treatment for MPNST between 1974 and 2012 at the authors' institution.

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Pancreatic cancer (PC) is a highly lethal disease, in part because of early metastasis, late diagnosis, and limited treatment options. Circulating tumor cells (CTCs) are cancer cells that have achieved the metastatic step of intravasation, and are thus a unique source of biomarkers with potential applications in the staging, prognostication, and treatment of PC. Areas covered: This review describes the use of CTCs in PC, including isolation methods, the significance of CTC enumeration, and studies examining phenotypic and molecular characteristics of CTCs.

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  • High-throughput screening techniques have significantly advanced our ability to engineer proteins with new properties, particularly in modifying enzymes for producing various products.
  • The researchers developed a high-throughput, genetically regulated screening method for producing β-lactam antibiotics, which uses a green fluorescent protein (GFP) reporter and allows for sensitive detection of different β-lactam subclasses.
  • The study successfully demonstrated this method in vivo and provided insights into a key catalytic residue in carbapenem synthase, offering valuable information for future enzyme activity studies and engineering efforts.
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