tbuckley/cabot-search huggingface dataset:
Abstract A028: Precise monitoring of osteosarcoma patients by noninvasive assessment of matrix metalloproteinases activities in plasma extracellular vesicles
Authors: Junseok Lee, You-Ren Ji, Hyoyong Kim, Zhao Chen, Ryan Zhang, Diego Banuet, Yusef Mathkour, Kenny Vo, Steven Jonas, Yazhen Zhu, Hsian-Rong Tseng
Journal: Clinical Cancer Research (2024)

Abstract Osteosarcoma (OS) is the most prevalent bone cancer in children, characterized by aggressive primary tumors and high metastatic potential. Current treatment protocols involve a combination of neoadjuvant chemotherapy, surgery, and adjuvant chemotherapy, tailored based on histological grade and metastatic risk. Identifying metastatic lesions through routine imaging significantly impacts treatment outcomes, highlighting the need for innovative diagnostic tools for timely monitoring. Noninvasive in vitro diagnostics, analyzing circulating tumor components like tumor-derived extracellular vesicles (EVs), would offer promise for monitoring treatment responses in pediatric sarcomas. Matrix metalloproteinases (MMPs) play a crucial role in tumor progression by degradation of the extracellular matrix; thus, recent research has focused on understanding their functional roles by profiling their proteolytic activities. Tumor EVs are crucial in transporting MMPs to facilitate invasion and metastasis, making them suitable surrogate for noninvasive profiling of MMP activities. Herein, we introduce an innovative OS EV MMP Activity Assay to assess MMP activities in OS patients noninvasively. This assay evaluates six different combinations of surface markers on OS EVs and OS-associated MMPs, generating a unique profile for each patient. Using a logistic regression model, an OS EV MMP Activity Score is generated from the most effective combinations. This Score has shown excellent performance in distinguishing between metastatic and localized OS. In a longitudinal study of six OS patients undergoing treatment, the Score strongly correlated with treatment response as measured by routine imaging. The assay represents a significant advancement in harnessing tumor EVs for diagnostics, providing a noninvasive, quantitative, and reliable approach to assess MMP activities in solid tumors. Citation Format: Junseok Lee, You-Ren Ji, Hyoyong Kim, Zhao Chen, Ryan Zhang, Diego Banuet, Yusef Mathkour, Kenny Vo, Steven Jonas, Yazhen Zhu, Hsian-Rong Tseng. Precise monitoring of osteosarcoma patients by noninvasive assessment of matrix metalloproteinases activities in plasma extracellular vesicles [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A028.
Abstract A005: Microbind affinity blood filter platform technology with affinity for heparan sulfate rapidly removes circulating epithelial tumor and cancer stem cells while downregulating VEGF A in patients with advanced and refractory solid tumors
Authors: Sanja ILIC, Vedran Premuzic, Robert Ward
Journal: Clinical Cancer Research (2024)

Abstract Background: Vascular endothelial-derived growth factor A(VEGFA) has been proven to be integral in the molecular pathogenesis of metastasis and tumor growth. It is known that VEGF is responsible for encoding a heparin-binding protein, which exists as a disulfide-linked homodimer which serves to promote the propagation and movement of vascular endothelial cells. This is essential for both pathological and physiological angiogenesis. CETC and cancer stem cells are potent secretors of VEGFA which is an essential cytokine that facilitates new vascular vessel formation, thus further enabling metastatic tumor growth. Methods: We developed a new extracorporeal microbind affinity blood filter platform technology with active heparane sulfate receptors (onco seraph). Heparin is cleaved into short chains which are permanently covalently bound to ultrahigh molecular weight polyethylene (UHMWPE) surfaces to create a new composition of matter. Liquid biopsy established high capacity for the rapid removal of CETC and PDAC cancer stem cells. Onco seraph was investigated in a dose escalation phase I/II clinical trial in adult patients with advanced and relapsed/refractory solid (what) and/or PDAC after standard of care and other lines of therapy failed in preventing disease progression. Results: To date 12 patients have been treated with onco seraph. No patient experienced treatment related adverse effects. Best responses include complete responses and stable disease at a low oncoseraph dose. Greatest efficacy was observed for patients whose liquid biopsy revealed significant and rapid reduction of CETC and cancer stem cells, followed by greater than 50% reduction in circulating VEGFA. Conclusions: This data supports the conclusion that the onco seraph platform technology is safe and has a high therapeutic value as an extracorporeal treatment for metastatic solid tumors refractory to standard of care. Citation Format: Sanja ILIC, Vedran Premuzic, Robert Ward. Microbind affinity blood filter platform technology with affinity for heparan sulfate rapidly removes circulating epithelial tumor and cancer stem cells while downregulating VEGF A in patients with advanced and refractory solid tumors [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A005.
Abstract A021: Analytical platform to validate microRNA cancer biomarkers
Authors: Anastassia Kanavarioti, M. Hassaan Rehman, Salma Qureshi, Aleena Rafiq, Madiha Sultan
Journal: Clinical Cancer Research (2024)

Abstract We developed and tested a novel assay to quantify and validate microRNA (miRNA) cancer biomarkers in liquid biopsies. The assay is amplification-free, exploits a commercially available nanopore-array device for detection (MinION from Oxford Nanopore Technologies), uses total RNA isolated from biospecimen as the miRNA source, and proprietary osmylated oligonucleotides, complementary to the target miRNA, as probes. The assay exploits a bracketing experimental protocol to quantify miRNA, and yields miRNA copy numbers (copies) per 1microLiter of isolated total RNA, with an unprecedented accuracy of approximately +/- 20% across all concentrations. For development purposes and as a control/reference the combined serum of healthy men (# H6914 from Sigma-Aldrich) was used. During a period of 4 years different lots of H6914 yielded, within experimental error, comparable miRNA copies for let-7b, miR-16, miR-21, miR-15b, miR-375 and miR-141. Serum samples from healthy individuals and cancer patients were also tested. Once data were normalized to the same total RNA content, miRNA copies appeared to belong to one of two groups. The first group included miR-21, miR-375 and miR-141 copies in H6914 and in healthy samples. The second group included miR-21, miR-375 and miR-141 copies in cancer samples exhibiting an approximate 1.8-fold overexpression compared to the first group. miR-15b copies in H6914, healthy and cancer samples were all in the first group. The two groups exhibited zero data overlap which is unprecedented in the miRNA/cancer literature. Zero data overlap was the result of (i) the assay’s bracketing approach with a protocol-defined accuracy of approximately +/-20%, and (ii) the normalization of miRNA copies to the same total RNA content. Notably, these two groups included both serum and urine samples from cancer patients and healthy individuals. All subjects were deselected regarding age, sex, and ethnicity, while patients were selected for breast, prostate or pancreatic cancer, Stage I or II, pretreatment. To the best of our knowledge, this is the first-time agreement between serum and urine miRNA copies is reported and leads to the suggestion that a urine sample may replace a blood draw for the tested miRNAs. Not only clear discrimination between healthy and cancer samples was possible, but this analytical platform may be used to validate tentative cancer/disease biomarkers when miRNA overexpression between cancer/disease and healthy is equal or higher than 1.8-fold. Non-Coding RNA 2024, 10(4), 42; https://doi.org/10.3390/ncrna10040042 Citation Format: Anastassia Kanavarioti, M. Hassaan Rehman, Salma Qureshi, Aleena Rafiq, Madiha Sultan. Analytical platform to validate microRNA cancer biomarkers [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A021.
Abstract A013: Quality control of the biobanked matched tissue: Blood samples for the development of diverse liquid based molecular assays
Authors: Zoran Gatalica, Phillip Stafford, Chris Diehnelt, Inga Rose
Journal: Clinical Cancer Research (2024)

Abstract The availability of high-quality matched biological samples (tumor-blood) is the major limiting factor for research and development of novel, liquid biopsy-based assays in oncology. Frequently, ongoing specifically timed collections of blood samples are required. De-identified tissue blocks (formalin-fixed, paraffin embedded (FFPE) or flash frozen) matched with patient's blood samples collected in fixative-containing (Streck) of EDTA containing tubes, were collected at worldwide geographic locations and transferred to biobanking facility (Reference Medicine, Phoenix, AZ). Additional blood samples were collected at various times regarding the cancer surgery. Plasma and buffy coat samples were locally prepared and shipped to the biobank. A subset of blood samples without matched tissues from healthy donors were also collected. All samples were shipped under strict transport conditions. Quality control performed at the biobanking facility included pathology review and nucleic acids quality assessment. A total of over 3,000 cases were collected and provided to end-users working on various assays based on cfDNA (e.g. monitoring for minimal residual disease or multi-cancer early detection). Immuno-reactivity to various antigens in samples collected in Streck and EDTA tubes (from 50 patients) was assessed by peptide microarray binding assay. Feedback information on the quality of samples was shared in 900 cases. Approximately 4% of cases had failed internal pathology review, due to poor preservation, lack of adequate tissue composition, or low tumor volume and 11% failed internal nucleic acid quality assessment (DNA concetration and integrity). The blood collection tubes had no significant impact on serologic testing using peptide microarary assay. Customer feedback data showed that overall success rate exceeded 85%. Type of blood collection tubes (Streck vs EDTA) had no impact on serologic testing and studies looking at predicted neoantigens based on NGS data can be confirmed using peptide epitope arrays. Blood collected for NGS works without compromise on peptide arrays. Future validation of other collection tubes for blood or other types of fluids is needed to confirm their adequacy for specific assays. Citation Format: Zoran Gatalica, Phillip Stafford, Chris Diehnelt, Inga Rose. Quality control of the biobanked matched tissue: Blood samples for the development of diverse liquid based molecular assays [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A013.
A microfluidic coculture model for mapping signaling perturbations and precise drug screening against macrophage-mediated dynamic myocardial injury
Authors: Zhao Gao, Zhiyong Du, Yu Hou, Kun Hua, Pengfei Tu, Xiaoni Ai, Yong Jiang
Journal: Acta Pharmaceutica Sinica B (2024)

Macrophage-mediated inflammation plays a pivotal role in cardiovascular disease pathogenesis. However, current cell-based models lack a comprehensive understanding of crosstalk between macrophages and cardiomyocytes, hindering the discovery of effective therapeutic interventions. Here, a microfluidic model has been developed to facilitate the coculture of macrophages and cardiomyocytes, allowing for mapping key signaling pathways and screening potential therapeutic agents against inflammation-induced dynamic myocardial injury. Through metabolic profiling and bioinformatic enrichment analysis, the microchip model with dynamic cell-cell crosstalk reveals robust activation of inflammatory and oxidative stress-associated metabolic pathways, closely resembling metabolic profiles of myocardial infarction in both humans and rodents. Furthermore, an integrative screening strategy has been established to screen bioactive natural products precisely, identifying ginsenoside Rb1 and protocatechualdehyde as promising cardioprotective candidates in vitro and in vivo. Taken together, the microfluidic coculture model advances mechanistic insight into macrophage-mediated cardio-immunology and may accelerate the discovery of therapeutics for myocardial injury.
Oncology Survivorship Care Clinics: Design and Implementation of Survivorship Care Delivery Systems at NCCN Member Institutions
Authors: Lindsey Bandini, Rebecca Caires, Linda Jacobs, Dori Klemanski, Donna Berizzi, Sheetal Kircher, Rachael Schmidt, Jessica Sugalski, Crystal S. Denlinger, Susan Brown
Journal: Journal of the National Comprehensive Cancer Network (2024)

It is estimated that there are >18 million cancer survivors in the United States, and there is a growing number of survivorship programs across the country to care for these individuals. There is a clear need for survivorship care; however, evidence is still emerging on how to best operationalize the guidance from nationally recognized organizations and clinical practice guidelines.
Local Recurrence and Survival in Patients With Melanoma &gt;2 mm in Thickness at Difficult Sites Treated With 1-cm Versus 2-cm Margins
Authors: Andrea Maurichi, Francesco Barretta, Roberto Patuzzo, Gianfranco Gallino, Ilaria Mattavelli, Michal Shimonovitz-Moore, Eran Nizri‏, Matteo Matteucci, Valeria Summo, Mara Cossa, Barbara Valeri, Umberto Cortinovis, Rosalba Miceli, Mario Santinami
Journal: Journal of the National Comprehensive Cancer Network (2024)

Background: Melanoma guidelines recommend surgical excision with 2-cm margins for melanomas &gt;2 mm in thickness. However, this procedure may be problematic at critical anatomic sites. We aimed to compare the outcomes of wide (2 cm) versus narrow (1 cm) excision margins in patients with melanoma &gt;2 mm in thickness near critical structures. Patients and Methods: We retrospectively examined 736 patients undergoing excision with wide versus narrow margins at the National Cancer Institute in Milan, Italy, between 2001 and 2015. Results: A total of 265 (36.0%) patients received a wide local excision—82 (30.9%) with linear repair and 183 (69.1%) with flap or graft reconstruction. A total of 471 (64.0%) patients received a narrow excision—320 (67.9%) with linear repair and 151 (32.1%) with flap or graft reconstruction ( P &lt;.001). The 10-year overall survival rate was 69.5% (95% CI, 63.3%–76.2%) in the wide group and 68.7% (95% CI, 63.8%–74.0%) in the narrow group ( P =.462); 10-year crude cumulative incidence (CCI) of local recurrence was 5.4% (95% CI, 3.2%–9.2%) in the wide and 8.8% (95% CI, 6.4%–12.1%) in the narrow group ( P =.150). Multivariable Fine-Gray modeling of the CCI of local recurrence showed that Breslow thickness ( P =.010) was the only statistically significant parameter. Multivariable Cox models for overall survival showed that age ( P &lt;.001), Breslow thickness ( P &lt;.001), and sentinel lymph node status ( P =.019) were statistically significant covariates. Excision margin was not a significant parameter affecting patients’ outcome. Conclusions: Wide local excision with 1-cm margins for melanoma &gt;2 mm in thickness was not associated with an increased risk of local recurrence and did not affect overall survival.
Echocardiographic Markers of Early Left Ventricular Dysfunction in Asymptomatic Aortic Regurgitation
Authors: Vidhu Anand, Hector I Michelena, Christopher G Scott, Alexander T Lee, Vera H Rigolin, Sorin V Pislaru, Garvan C Kane, Juan A Crestanello, Patricia A Pellikka
Journal: JACC. Cardiovascular imaging (2024)
Animal models of Long Covid: A hit-and-run disease
Authors: Alexandra Schäfer, Sarah R. Leist, John M. Powers, Ralph S. Baric
Journal: Science Translational Medicine (2024)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) pandemic has caused more than 7 million deaths globally. Despite the presence of infection- and vaccine-induced immunity, SARS-CoV-2 infections remain a major global health concern because of the emergence of SARS-CoV-2 variants that can cause severe acute coronavirus disease 2019 (COVID-19) or enhance Long Covid disease phenotypes. About 5 to 10% of SARS-CoV-2-infected individuals develop Long Covid, which, similar to acute COVID 19, often affects the lung. However, Long Covid can also affect other peripheral organs, especially the brain. The causal relationships between acute disease phenotypes, long-term symptoms, and involvement of multiple organ systems remain elusive, and animal model systems mimicking both acute and post-acute phases are imperative. Here, we review the current state of Long Covid animal models, including current and possible future applications.
Infection-associated chronic conditions: Why Long Covid is our best chance to untangle Osler’s web
Authors: Michael J. Peluso, Maureen R. Hanson, Steven G. Deeks
Journal: Science Translational Medicine (2024)

The recognition of Long Covid has renewed efforts to understand other infection-associated chronic conditions (IACCs). Here, we describe how studies of Long Covid and other IACCs might inform one another. We argue for the importance of a coordinated research agenda addressing these debilitating illnesses.
Translating insights into therapies for Long Covid
Authors: Annukka A. R. Antar, Andrea L. Cox
Journal: Science Translational Medicine (2024)

Long Covid is defined by a wide range of symptoms that persist after the acute phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Commonly reported symptoms include fatigue, weakness, postexertional malaise, and cognitive dysfunction, with many other symptoms reported. Symptom range, duration, and severity are highly variable and partially overlap with symptoms of myalgic encephalomyelitis/chronic fatigue syndrome and other post-acute infectious syndromes, highlighting opportunities to define shared mechanisms of pathogenesis. Potential mechanisms of Long Covid are diverse, including persistence of viral reservoirs, dysregulated immune responses, direct viral damage of tissues targeted by SARS-CoV-2, inflammation driven by reactivation of latent viral infections, vascular endothelium activation or dysfunction, and subsequent thromboinflammation, autoimmunity, metabolic derangements, microglial activation, and microbiota dysbiosis. The heterogeneity of symptoms and baseline characteristics of people with Long Covid, as well as the varying states of immunity and therapies given at the time of acute infection, have made etiologies of Long Covid difficult to determine. Here, we examine progress on preclinical models for Long Covid and review progress being made in clinical trials, highlighting the need for large human studies and further development of models to better understand Long Covid. Such studies will inform clinical trials that will define treatments to benefit those living with this condition.
Sex differences and immune correlates of Long Covid development, symptom persistence, and resolution
Authors: Rebecca E. Hamlin, Shaun M. Pienkos, Leslie Chan, Mikayla A. Stabile, Kassandra Pinedo, Mallika Rao, Philip Grant, Hector Bonilla, Marisa Holubar, Upinder Singh, Karen B. Jacobson, Prasanna Jagannathan, Yvonne Maldonado, Susan P. Holmes, Aruna Subramanian, Catherine A. Blish
Journal: Science Translational Medicine (2024)

Sex differences have been observed in acute coronavirus disease 2019 (COVID-19) and Long Covid (LC) outcomes, with greater disease severity and mortality during acute infection in males and greater proportions of females developing LC. We hypothesized that sex-specific immune dysregulation contributes to LC pathogenesis. To investigate the immunologic underpinnings of LC development and symptom persistence, we performed multiomic analyses on blood samples obtained during acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and 3 and 12 months after infection in a cohort of 45 participants who either developed LC or recovered. Several sex-specific immune pathways were associated with LC. Males who would later develop LC exhibited increases in transforming growth factor-β (TGF-β) signaling during acute infection, whereas females who would go on to develop LC had reduced
Consequences beyond acute SARS-CoV-2 infection in children
Authors: Sharon H. Saydah, Angela P. Campbell, Adrienne G. Randolph
Journal: Science Translational Medicine (2024)

Although most children are spared from developing complications from SARS-CoV-2 infection, some may suffer consequences including Long Covid and multisystem inflammatory syndrome in children (MIS-C). Although the occurrence of these conditions has decreased over time, they can still occur, and recognition of symptoms and prompt diagnosis is imperative for early intervention.
Symptoms after Lyme disease: What’s past is prologue
Authors: Adriana Marques
Journal: Science Translational Medicine (2024)

Protracted fatigue and other symptoms can occur after Lyme disease and other infections, with numerous possible drivers. Studies on posttreatment Lyme disease have been inconclusive, with no confirmed biomarker emerging. Prolonged antibiotic therapy provides no benefit. Thus, a holistic approach toward understanding and treating this complex disease is necessary.
ArtiSentialⓇ versus conventional laparoscopic colorectal cancer surgery: a multicenter retrospective matched cohort study
Authors: Dae Hee Pyo, Yoon Suk Lee, Byung Soh Min, Jaeim Lee, Chang Hyun Kim, Heung-Kwon Oh, Yong Sik Yoon, Donghwan Bae, Jung Wook Huh
Journal: International Journal of Surgery (2024)

This study aims to compare outcomes of colorectal cancer surgeries performed using the newly developed articulating laparoscopic instrument, ArtiSential, with those using conventional non-articulating or rigid laparoscopic instruments. This multicenter, retrospective, matched cohort study enrolled patients with colorectal cancer undergoing laparoscopic surgery in seven tertiary referral hospitals from January 2021 to October 2022. A 1:1 propensity score matching was performed between the articulating (Arti-LAP) and conventional (Rigid-LAP) laparoscopic groups. The primary outcome was the overall incidence of short-term complications. The study initially comprised 694 and 2008 patients in the Arti-LAP and Rigid-LAP groups, respectively. After matching, each group consisted of 694 patients, with no significant differences in baseline clinical characteristics. The mean operation time was 161±32 min in Arti-LAP and 152±25 min in Rigid-LAP groups (P=0.105). Open conversion rates were 0% (0/694) in Arti-LAP and 1.0% (7/694) in Rigid-LAP groups (P=0.024). Overall morbidity rates were 9.5% (66/694) in Arti-LAP and 12.8% (89/694) in Rigid-LAP (P=0.061), with similar rates of severe morbidities. Specimen quality was acceptable in both groups. Multivariable regression analysis showed that the choice of instrument type (articulating or rigid) was not associated with perioperative morbidity. Despite a short median follow-up period of 19.5 months, no significant difference in disease-free survival was observed between the groups. Laparoscopic surgery using ArtiSential was performed safely and effectively for patients with colorectal cancer. Articulating laparoscopic instruments may offer an advantage in reducing open conversion rates.