Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, largely due to its dense fibrotic stroma that promotes drug resistance and tumor progression. While patient-derived organoids (PDOs) have emerged as promising tools for modeling PDAC and evaluating therapeutic responses, the current PDO models grown in soft matrices fail to replicate the tumor's stiff extracellular matrix (ECM), limiting their predictive value for advanced disease.
Methods: We developed a biomimetic model using gelatin-based matrices of varying stiffness, achieved through modulated transglutaminase crosslinking rates, to better simulate the desmoplastic PDAC microenvironment.
Background & Purpose: Current treatments for falls in people with multiple sclerosis (PwMS) are incompletely effective. Reactive balance can prevent falls after a loss of balance and is negatively impacted by MS. Perturbation training may improve reactive balance.
View Article and Find Full Text PDFObjectives: Black/African American (B/AA) pancreatic ductal adenocarcinoma (PDAC) patients have worse clinical outcomes than White patients and are underrepresented in genomic databases. We aimed to expand our understanding of the PDAC somatic landscape from a diverse cohort.
Materials And Methods: Formalin-fixed paraffin-embedded specimens from 24 surgically resected PDAC cases were collected, with self-reported race/ethnicity.
Pancreatic ductal adenocarcinoma is projected to become the second leading cause of cancer-related deaths by 2040, with the highest disease burden expected amongst Non-Hispanic Blacks. One of the most significant predictors of poor outcomes is the presence of cancer-associated cachexia (CCa). Yet, race- and ethnicity-specific biomarkers for early CCa diagnosis are lacking.
View Article and Find Full Text PDFEarly pregnancy loss (EPL) occurs in 15% to 20% of clinically recognized pregnancies. We recommend that patients experiencing EPL have equal access to all treatment options, including expectant, medication, and procedural management, when urgent treatment is not necessary (GRADE 1A). We recommend a patient-centered approach that uses shared decision-making to diagnose EPL through ultrasonography, serial quantitative hCG measurements, or symptoms (GRADE 1C).
View Article and Find Full Text PDFDespite many decades of research, pancreatic ductal adenocarcinoma (PDAC) remains one of the most difficult cancers to diagnose and treat effectively. Although there have been improvements in the 5-year overall survival rate, it is still very low at 12.5%.
View Article and Find Full Text PDFBackground: Open cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a therapeutic option for the management of malignancies with peritoneal carcinomatosis and of peritoneal origin. Robotic surgery shows promise as a minimally invasive approach for select patients. We aimed to evaluate the differences in outcomes between robotic versus open CRS/HIPEC and hypothesized less morbidity and faster recovery in the robotic approach group.
View Article and Find Full Text PDFIntroduction: Cancer-associated cachexia (CC) is a progressive syndrome characterized by unintentional weight loss, muscle atrophy, fatigue, and poor outcomes that affects most patients with pancreatic ductal adenocarcinoma (PDAC). The ability to identify and classify CC stage along its continuum early in the disease process is challenging but critical for management.
Objectives: The main objective of this study was to determine the prevalence of CC stage overall and by sex and race and ethnicity among treatment-naïve PDAC cases using clinical, nutritional, and functional criteria.
Muscle atrophy and weakness are prevalent features of cancer. Although extensive research has characterized skeletal muscle wasting in cancer cachexia, limited studies have investigated how cardiac structure and function are affected by therapy-naive cancer. Herein, orthotopic, syngeneic models of epithelial ovarian cancer and pancreatic ductal adenocarcinoma, and a patient-derived pancreatic xenograft model, were used to define the impact of malignancy on cardiac structure, function, and metabolism.
View Article and Find Full Text PDFIntroduction: The perceptions of teaching faculty toward pregnant general surgery residents have been overlooked despite the daily interactions amongst these groups.
Methods: A 32-question survey designed to measure general surgery teaching faculty perceptions toward pregnant residents was distributed electronically from March 2022 to April 2022 to general surgery teaching faculty in the United States. Descriptive statistics were used to characterize responses and differences in perceptions, and qualitative analysis identified recurring themes from free-text responses.
CD8+ T cell dysfunction impedes antitumor immunity in solid cancers, but the underlying mechanisms are diverse and poorly understood. Extracellular matrix (ECM) composition has been linked to impaired T cell migration and enhanced tumor progression; however, impacts of individual ECM molecules on T cell function in the tumor microenvironment (TME) are only beginning to be elucidated. Upstream regulators of aberrant ECM deposition and organization in solid tumors are equally ill-defined.
View Article and Find Full Text PDFAlthough patient-derived xenografts (PDX) are commonly used for preclinical modeling in cancer research, a standard approach to in vivo tumor growth analysis and assessment of antitumor activity is lacking, complicating the comparison of different studies and determination of whether a PDX experiment has produced evidence needed to consider a new therapy promising. We present consensus recommendations for assessment of PDX growth and antitumor activity, providing public access to a suite of tools for in vivo growth analyses. We expect that harmonizing PDX study design and analysis and assessing a suite of analytical tools will enhance information exchange and facilitate identification of promising novel therapies and biomarkers for guiding cancer therapy.
View Article and Find Full Text PDFBackground: The rotator cable functions as a stress and/or load transfer structure. Some studies suggested that a disruption of the cable negatively affects shoulder function and tendon integrity in patients with rotator cuff tears, while others found no functional impairment regardless of rotator cable tear severity. Although anatomical studies have identified distinct regions within the rotator cuff muscles, the strain distribution within the articular sides of the rotator cuff tendons that results from the tension in each region remains unknown.
View Article and Find Full Text PDFBackground: Pancreatic ductal adenocarcinomas (PDAC) have heterogeneous tumor microenvironments relatively devoid of infiltrating immune cells. We aimed to quantitatively assess infiltrating CD3+ and CD8+ lymphocytes in a treatment-naïve patient cohort and assess associations with overall survival and microenvironment inflammatory proteins.
Methods: Tissue microarrays were immunohistochemically stained for CD3+ and CD8+ lymphocytes and quantitatively assessed using QuPath.
Lung cancer is the third most common cancer with Black/AA men showing higher risk and poorer outcomes than NHW men. Lung cancer disparities are multifactorial, driven by tobacco exposure, inequities in care access, upstream health determinants, and molecular determinants including biological and genetic factors. Elevated expressions of protein arginine methyltransferases (PRMTs) correlating with poorer prognosis have been observed in many cancers.
View Article and Find Full Text PDF•Metastatic disease to the small bowel may present with intussusception.•Clinical decision making for malignant bowel obstruction is difficult and individual specific.•Malignant bowel obstruction due to metastatic year has an average life expectancy of less than 200 days.
View Article and Find Full Text PDFJ Cachexia Sarcopenia Muscle
February 2024
Background: Pancreatic ductal adenocarcinoma (PDAC) is highly associated with cachexia and weight loss, which is driven by the tumour's effect on the body. Data are lacking on differences in these metrics based on PDAC anatomic location. We hypothesize that the primary tumour's anatomic region influences the prevalence and severity of unintentional weight loss.
View Article and Find Full Text PDFUnlabelled: Currently, there are no clinically approved drugs that directly thwart mutant KRAS G12D, a major driver of human cancer. Here, we report on the discovery of a small molecule, KRB-456, that binds KRAS G12D and inhibits the growth of pancreatic cancer patient-derived tumors. Protein nuclear magnetic resonance studies revealed that KRB-456 binds the GDP-bound and GCP-bound conformation of KRAS G12D by forming interactions with a dynamic allosteric binding pocket within the switch-I/II region.
View Article and Find Full Text PDFPurpose: To quantify the burden of ocular injuries on deployed US service members by calculating disability-adjusted life years (DALYs).
Design: Retrospective, observational cohort study.
Participants: US service members with ocular injuries sustained in combat zones from January 1, 2001 to May 19, 2020.
Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer without effective therapies and with poor prognosis, causing 7% of all cancer-related fatalities in the USA. Considering the lack of effective therapies for this aggressive cancer, there is an urgent need to define newer and more effective therapeutic strategies. Polyinosine-polycytidylic acid (pIC) is a synthetic double-stranded RNA (dsRNA) which directly activates dendritic cells and natural killer cells inhibiting tumor growth.
View Article and Find Full Text PDFCells have evolved their communication methods to sense their microenvironments and send biological signals. In addition to communication using ligands and receptors, cells use diverse channels including gap junctions to communicate with their immediate neighbors. Current approaches, however, cannot effectively capture the influence of various microenvironments.
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