Tumor-Associated Carbohydrate Antigen 19-9 (CA 19-9), a Promising Target for Antibody-Based Detection, Diagnosis, and Immunotherapy of Cancer.

Carbohydrate antigen 19-9 (CA 19-9) also known as sialyl Lewis A is a tetrasaccharide overexpressed on a wide range of cancerous cells, which has been detected at elevated levels in sera of patients with various types of malignancies, most prominently pancreatic ductal adenocarcinoma. After its identification in 1979, multiple studies have highlighted the significant roles of CA 19-9 in cancer progression, including facilitating extravasation and eventually metastases, proliferation of cancer cells, and suppression of the immune system. Therefore, CA 19-9 has been considered an attractive target for cancer diagnosis, prognosis, and therapy. This review discusses the synthesis of CA 19-9 antigen, elicitation of antibodies through vaccination, development of anti-CA 19-9 monoclonal antibodies, and their applications as imaging tracers and therapeutics for a variety of CA 19-9-positive cancer.

Tantalum oxide nanoparticles as versatile and high-resolution X-ray contrast agent for intraductal image-guided ablative procedure in rodent models of breast cancer.

There are limited options for primary prevention of breast cancer (BC). Experimental procedures to locally prevent BC have shown therapeutic efficacy in animal models. To determine the suitability of FDA-approved iodine-containing and various metal-containing (bismuth, gold, iodine, or tantalum) preclinical nanoparticle-based contrast agents for image-guided intraductal (ID) ablative treatment of BC in rodent models, we performed a prospective longitudinal study to determine the imaging performance, local retention and systemic clearance, safety profile, and compatibility with ablative solution of each contrast agent. At least six abdominal mammary glands (>3 female FVB/JN mice and/or Sprague-Dawley rats, 10-11 weeks of age) were intraductally injected with commercially available contrast agents (Omnipaque® 300, Fenestra® VC, MVivoTM Au, MVivoTM BIS) or in-house synthesized tantalum oxide (TaOx) nanoparticles. Contrast agents were administered at stock concentration or diluted in 70% ethanol (EtOH) and up to 1% ethyl cellulose (EC) as gelling agent to assess their compatibility with our image-guided ablative procedure. Mammary glands were serially imaged by microCT for up to 60 days after ID delivery. Imaging data were analyzed by radiologists and deep learning to measure in vivo signal disappearance of contrast agents. Mammary glands and major organs were ultimately collected for histopathological examination. TaOx-containing solutions provided best imaging performance for nitid visualization of ductal tree immediately after infusion, low outward diffusion (<1 day) and high homogeneity. Of all nanoparticles, TaOx had the highest local clearance rate (46% signal decay as stock and 36% as ablative solution 3 days after ID injection) and exhibited low toxicity. TaOx-containing ablative solution with 1% EC caused same percentage of epithelial cell death (88.62% ± 7.70% vs. 76.38% ± 9.99%, p value = 0.089) with similar minimal collateral damage (21.56 ± 5.28% vs. 21.50% ± 7.14%, p value = 0.98) in mouse and rat mammary glands, respectively. In conclusion, TaOx-nanoparticles are a suitable and versatile contrast agent for intraductal imaging and image-guided ablative procedures in rodent models of BC with translational potential to humans.

Efficacy of subcutaneous sumatriptan in postcraniotomy pain and opioid consumption.

OBJECTIVE: Traditional pain management pathways following craniotomy are predicated on opioids. However, narcotics can confound critical neurological examination, contribute to respiratory depression, lower the seizure threshold, and lead to medication habituation, dependence, and/or abuse. Alternative medications to better address postoperative pain while mitigating opioid-related adverse effects remain insufficiently studied. Preliminary studies suggest sumatriptan, a 5-HT (1B/1D) receptor agonist known to regulate dural vasoactivity and inflammation, may moderate pain following trigeminal microvascular decompression and chronic postcraniotomy headache. In this study, the authors evaluated the efficacy of sumatriptan to modulate pain and opioid requirements following craniotomy surgery. METHODS: This was a single academic center, retrospective cohort study of 300 consecutive adult patients who underwent elective craniotomy surgery between 2015 and 2022. Patients were equally divided between a control and a sumatriptan cohort contingent upon administration of 6 mg of subcutaneous sumatriptan within 1 hour of surgery completion and prior to opioid administration. Postoperative opioid consumption at 6, 12, and 24 hours, as well as admission total, inpatient length of stay, and 30-day global reevaluation, were assessed. RESULTS: Three hundred patients were included for analysis. Significant differences were seen in baseline hypertension (p < 0.01), hyperlipemia (p < 0.01), anxiety (p = 0.04), and operative time (p = 0.02). A significant reduction of mean postoperative pain scores at 12 (p = 0.03) and 24 (p < 0.01) hours and total opioid consumption (p = 0.04) was observed in the sumatriptan cohort. Subgroup analysis revealed significantly lower postoperative pain scores at 6 (p = 0.05), 12 (p < 0.01), and 24 (p < 0.01) hours in patients who underwent burr hole placement in the sumatriptan cohort as compared with controls; however, no significant difference in opioid consumption was noted. No adverse events related to sumatriptan administration were noted throughout the study. CONCLUSIONS: Postoperative single-dose subcutaneous sumatriptan following elective craniotomy may reduce pain scores and opioid requirements. Additional studies are needed to better understand nuanced differences in opioid modulation and optimal patient selection.

The Regulation of MicroRNA-21 by Interleukin-6 and Its Role in the Development of Fibrosis in Endometriotic Lesions.

Endometriosis is one of the most common causes of chronic pelvic pain and infertility that affects 10% of women of reproductive age. It is currently defined as the presence of endometrial epithelial and stromal cells at ectopic sites; however, advances in endometriosis research have some authors believing that endometriosis should be re-defined as "a fibrotic condition in which endometrial stroma and epithelium can be identified". microRNAs (miRNAs) are regulatory molecules that potentially play a role in endometriotic lesion development. There is evidence that suggests that miRNAs, including microRNA-21 (miR-21), participate in fibrotic processes in different organs, including the heart, kidney, liver and lungs. The objective of this study was to understand the role of miR-21 and the mechanisms that can contribute to the development of fibrosis by determining how IL-6 regulates miR-21 expression and how this miRNA regulates the transforming growth factor beta (TGF-ß) signaling pathway to promote fibrosis. We investigated the expression of miR-21 in the baboon and mouse model of endometriosis and its correlation with fibrosis. We demonstrated that inflammation and fibrosis are present at a very early stage of endometriosis and that the inflammatory environment in the peritoneal cavity, which includes interleukin 6 (IL-6), can regulate the expression of miR-21 in vitro and in vivo.

Systemic and Local Strategies for Primary Prevention of Breast Cancer.

One in eight women will develop breast cancer in the US. For women with moderate (15-20%) to average (12.5%) risk of breast cancer, there are few options available for risk reduction. For high-risk (>20%) women, such as BRCA mutation carriers, primary prevention strategies are limited to evidence-based surgical removal of breasts and/or ovaries and anti-estrogen treatment. Despite their effectiveness in risk reduction, not many high-risk individuals opt for surgical or hormonal interventions due to severe side effects and potentially life-changing outcomes as key deterrents. Thus, better communication about the benefits of existing strategies and the development of new strategies with minimal side effects are needed to offer women adequate risk-reducing interventions. We extensively review and discuss innovative investigational strategies for primary prevention. Most of these investigational strategies are at the pre-clinical stage, but some are already being evaluated in clinical trials and others are expected to lead to first-in-human clinical trials within 5 years. Likely, these strategies would be initially tested in high-risk individuals but may be applicable to lower-risk women, if shown to decrease risk at a similar rate to existing strategies, but with minimal side effects.

Shape Anisotropy-Governed High-Performance Nanomagnetosol for In Vivo Magnetic Particle Imaging of Lungs.

Caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coronavirus disease 2019 (COVID-19) has shown extensive lung manifestations in vulnerable individuals, putting lung imaging and monitoring at the forefront of early detection and treatment. Magnetic particle imaging (MPI) is an imaging modality, which can bring excellent contrast, sensitivity, and signal-to-noise ratios to lung imaging for the development of new theranostic approaches for respiratory diseases. Advances in MPI tracers would offer additional improvements and increase the potential for clinical translation of MPI. Here, a high-performance nanotracer based on shape anisotropy of magnetic nanoparticles is developed and its use in MPI imaging of the lung is demonstrated. Shape anisotropy proves to be a critical parameter for increasing signal intensity and resolution and exceeding those properties of conventional spherical nanoparticles. The 0D nanoparticles exhibit a 2-fold increase, while the 1D nanorods have a > 5-fold increase in signal intensity when compared to VivoTrax. Newly designed 1D nanorods displayed high signal intensities and excellent resolution in lung images. A spatiotemporal lung imaging study in mice revealed that this tracer offers new opportunities for monitoring disease and guiding intervention.

Confirmatory validation analysis of the PROFFIT questionnaire to assess financial toxicity in cancer patients.

BACKGROUND: The Patient Reported Outcome for Fighting FInancial Toxicity (PROFFIT) questionnaire was developed to measure financial toxicity (FT) and identify its determinants. The aim of the present study was to confirm its validity in a prospective cohort of patients receiving anticancer treatment. PATIENTS AND METHODS: From March 2021 to July 2022, 221 patients were enrolled at 10 Italian centres. Selected items of the EORTC-QLQ-C30 questionnaire represented the anchors, specifically, question 28 (Q-28) on financial difficulties, and questions 29-30 measuring global health status/quality of life (HR-QOL). The study had 80% power to detect a 0.20 correlation coefficient (r) between anchors and PROFFIT-score (items 1-7, range 0-100, 100 indicating maximum FT) with bilateral alpha 0.05 and 80% power. Confirmatory factor analysis was conducted. FT determinants (items 8-16) were described. RESULTS: Median age of patients was 65 years, 116 (52.5%) were females, 96 (43.4%) had low education level. Confirmatory factor analysis confirmed goodness of fit of the PROFFIT-score. Significant partial correlation of PROFFIT-score was found with Q-28 (r = 0.51) and HR-QOL (r = -0.23). Mean (SD) PROFFIT-score at baseline was 36.5 (24.9); it was statistically significantly higher for patients living in South Italy, those with lower education level, those who were freelancer/unemployed at diagnosis and those who reported significant economic impact from the COVID-19 pandemic. Mean (SD) scores of determinants ranged from 17.6 (27.1) for item 14 (support from medical staff) to 49.0 (36.3) for item 10 (expenses for medicines or supplements). PROFFIT-score significantly increased with worsening response to determinants. CONCLUSIONS: External validation of PROFFIT-score in an independent sample of patients was successful. The instrument is now being used in clinical studies.

Epidemiologic trends in hand injuries in the National Football League from 2009-2010 to 2019-2020.

OBJECTIVES: In American football, hand injuries have been shown to negatively impact performance. The purpose of this study is to characterize the prevalence and severity of hand injuries in National Football League (NFL) players. METHODS: A public online database was utilized to identify hand injuries in NFL players from 2009-2010 to 2019-2020. The primary outcome was to analyze the overall incidence of hand injuries (including wrist, metacarpus, finger, and thumb), injury type by each aforementioned anatomic location, and player position. Injury severity was evaluated based on percentage of injuries in which players returned to play (RTP), number of games missed before RTP, and the percentage of injuries resulting in the player being placed on injured reserve (IR). RESULTS: Of the 6,127 players included, 847 (13.8%) players sustained a hand injury, of which 24.8%, 34.3%, 17.9%, and 22.9% occurred at the wrist, metacarpus, finger, and thumb, respectively. Of the injured players, 97.4% returned to play following their injury, 14.8% were put on IR, and an average of 1.7 (SD 3.3) games were missed. Quarterbacks were the most likely to sustain hand injuries at all anatomic locations. Wrist injuries were associated with the lowest RTP rate (93.3%), the most players placed on injured reserve (28.6%), and the greatest number of games missed (mean 2.5, SD 4.2). CONCLUSION: Hand injuries decreased in prevalence by 65.6% over the 11 NFL seasons evaluated. This trend coincides with the implementation of several safety rules that relate to components of play involving the hands. Quarterbacks experienced the greatest prevalence and severity for all hand injuries. Wrist injuries represent the anatomic location associated with the greatest severity. These findings may be able to inform tailored injury prevention practices by position, and advocate for the further adoption of safety rules to protect players from further injury.

MicroRNA-210-3p Regulates Endometriotic Lesion Development by Targeting IGFBP3 in Baboons and Women with Endometriosis.

MicroRNAs (miRs) play an important role in the pathophysiology of endometriosis; however, the role of miR-210 in endometriosis remains unclear. This study explores the role of miR-210 and its targets, IGFBP3 and COL8A1, in ectopic lesion growth and development. Matched eutopic (EuE) and ectopic (EcE) endometrial samples were obtained for analysis from baboons and women with endometriosis. Immortalized human ectopic endometriotic epithelial cells (12Z cells) were utilized for functional assays. Endometriosis was experimentally induced in female baboons (n = 5). Human matched endometrial and endometriotic tissues were obtained from women (n = 9, 18-45 years old) with regular menstrual cycles. Quantitative reverse transcript polymerase chain reaction (RT-qPCR) analysis was performed for in vivo characterization of miR-210, IGFBP3, and COL8A1. In situ hybridization and immunohistochemical analysis were performed for cell-specific localization. Immortalized endometriotic epithelial cell lines (12Z) were utilized for in vitro functional assays. MiR-210 expression was decreased in EcE, while IGFBP3 and COL8A1 expression was increased in EcE. MiR-210 was expressed in the glandular epithelium of EuE but attenuated in those of EcE. IGFBP3 and COL8A1 were expressed in the glandular epithelium of EuE and were increased compared to EcE. MiR-210 overexpression in 12Z cells suppressed IGFBP3 expression and attenuated cell proliferation and migration. MiR-210 repression and subsequent unopposed IGFBP3 expression may contribute to endometriotic lesion development by increasing cell proliferation and migration.