tbuckley/cabot-search huggingface dataset:
Humanized anti-DEspR monoclonal antibody to improve overall survival in xenograft pancreatic peritoneal carcinomatosis nude rat model.
Authors: Christopher Gromisch, Matthew Stannard Gromisch, Mark Grinstaff, Victoria L.M. Herrera, Nelson Ruiz-Opazo
Journal: Journal of Clinical Oncology (2021)

e16262 Background: Pancreatic adenocarcinoma (PDAC) with peritoneal carcinomatosis (PPC) has the worst median overall survival (mOS) among all PDAC metastasis. Novel therapeutic approaches are needed for PPC. The Dual Endothelin-1/VEGF-signal-peptide Receptor (DEspR) is a cell surface receptor which regulates PDAC tumor cell and cancer stem-like cell (CSC) anoikis resistance, tumorigenicity, and tumoral angiogenesis. To translate these findings into a novel anti-cancer therapy, we evaluated the efficacy, empirical safety, pharmacokinetics, and pharmacodynamics of a recombinant, humanized, anti-DEspR hinge-stabilized IgG4 S228P monoclonal antibody, hu-6g8, in a PPC xenograft tumor nude rat model. Methods: We used a Panc1 CSC-derived xenograft tumor model of PPC developed via intraperitoneal injection of two million Panc1 CSCs functionally isolated for anoikis resistance. Isolated CSCs had variable DEspR expression, thus modeling CSC-heterogeneity. For efficacy studies, PPC-rats were randomized to receive a single intravenous injection of either 3mg/kg or 15mg/kg hu-6g8, 100mg/kg gemcitabine, or saline, given 3 weeks after CSC injection with palpable PPC tumors. Blood samples were collected to monitor for hematological adverse events (AEs) and vital organs were collected to evaluate for hu-6g8-induced apoptosis. Pharmacokinetics was assessed in a separate study cohort by sequential blood draws after rats received a single dose of 3 mg/kg or 15 mg/kg hu-6g8. In a 3 rd cohort, pharmacodynamics were assessed by vital organ collection and immunohistochemistry after rats received either a single-iv injection of 3mg/kg hu-6g8 or IgG4 isotype control. Results: Single dose 15 mg/kg hu-6g8 treatment significantly improved median overall survival (189 days, n = 0.0007) with 3 mg/kg hu-6g8 being comparable to 100 mg/kg gemcitabine (92 vs 115 days, n = 0.62). No hematological AEs were observed in hu-6g8 treated rats, and there was no evidence of increased apoptosis by hu-6g8 in normal tissues by immunohistochemistry of activated Caspase-3. Hu-6g8 demonstrated an average elimination half-life of 46.1 hrs in a two-compartment model. Biodistribution of the antibody showed predominant uptake, albeit heterogenous, and induction of activated caspase 3+ apoptosis in the peritoneal tumors by 24-hours with minimal off-target binding. Conclusions: Treatment with monoclonal hu-6g8 significantly improved survival in a model of PCC with excellent tumor specificity and minimal off-target effect.
The impact of COVID-19 on patients with cancer: A qualitative study.
Authors: Dhanya Kumar, Sana Khateeb, Manali I. Patel
Journal: Journal of Clinical Oncology (2021)

e18559 Background: The SARS‐CoV‐2/COVID‐19 pandemic greatly impacted the health of many patients with cancer. We conducted in-depth interviews with patients across the United States to better understand the effect of the COVID-19 pandemic on their cancer care, emotional and mental health, and to solicit suggestions for how health care providers could mitigate these concerns. Methods: We contacted respondents from the Impact of COVID-19 on Cancer parent study. The parent study used a snowball sampling approach to survey patients nationally regarding cancer delays between April 2020 and October 2020. We invited all respondents who volunteered for future studies to participate in a 40-minute interview regarding their experiences and suggestions for how health care providers could mitigate COVID19-related concerns. Interviews were conducted between August 2020 and October 2020, recorded, transcribed and analyzed using qualitative thematic content analysis. Results: A total of 34 participants were contacted and consented to participate in this study. Four overarching themes were identified: (1) significant concern regarding infection risk; (2) concerns regarding care changes, such as delays, worsening cancer outcomes; (3) concern regarding loss of employment, health insurance, and transportation on cancer treatment, affordability, and prognosis; and (4) worsening emotional and mental health due to social isolation. Suggestions for the clinical team included: 1) specific and direct guidance from health care providers on how to mitigate infection risk; 2) screening for and access to mental health services; 3) continuation of cancer treatment, surveillance, and clinical trials without delays and 4) allowing caregivers to attend appointments. Conclusions: In this national qualitative study of patients with cancer, participants identified that COVID-19 and modifications to their cancer care worsened their emotional and mental health with growing concerns about the impact of the virus and socioeconomic status on their cancer outcomes. Specific suggestions for health care providers, such as anticipatory guidance, access to mental health services, and expanded visitation should be considered to improve patient experiences with care during the pandemic.
Redox-sensitive hyaluronic acid-cholesterol nanovehicles potentiate efficient transmembrane internalization and controlled release for penetrated “full-line” inhibition of pre-metastatic initiation
Authors: Meirong Huo, Honglan Wang, Lingchao Li, Yuqing Tong, Chengxia Hu, Yongwei Gu, Jiyong Liu, Tingjie Yin
Journal: Journal of Controlled Release (2021)
EPCT-14. GD2 CAR T-CELLS MEDIATE CLINICAL ACTIVITY AND MANAGEABLE TOXICITY IN CHILDREN AND YOUNG ADULTS WITH H3K27M-MUTATED DIPG AND SPINAL CORD DMG
Authors: Robbie Majzner, Sneha Ramakrishna, Aaron Mochizuki, Shabnum Patel, Harshini Chinnasamy, Kristen Yeom, Liora Schultz, Rebecca Richards, Cynthia Campen, Agnes Reschke, Jasia Mahdi, Angus Martin Shaw Toland, Christina Baggott, Sharon Mavroukakis, Emily Egeler, Jennifer Moon, Kayla Landrum, Courtney Erickson, Lindsay Rasmussen, Valentin Barsan, John Tamaresis, Anne Marcy, Michael Kunicki, Michelle Fujimoto, Zach Ehlinger, Sreevidya Kurra, Timothy Cornell, Sonia Partap, Paul Fisher, Gerald Grant, Hannes Vogel, Bita Sahaf, Kara Davis, Steven Feldman, Crystal Mackall, Michelle Monje
Journal: Neuro-Oncology (2021)

Abstract Background We previously discovered high expression of the disialoganglioside GD2 on H3K27M+ gliomas and demonstrated preclinical efficacy of intravenous (IV) GD2-targeted chimeric antigen receptor (CAR) T-cells in preclinical models of H3K27M-mutated diffuse intrinsic pontine glioma (DIPG) and diffuse midline gliomas (DMGs). We are now conducting a Phase I clinical trial (NCT04196413) of autologous GD2-targeting CAR T-cells for H3K27M+ DIPG and spinal cord DMG. Here we present the results of subjects treated at dose level 1 (DL1; 1 million GD2-CAR T-cells/kg IV). Methods Four patients (3 DIPG, 1 spinal DMG; ages 4–25; 1M/3F) were enrolled at DL1. Three subjects with H3K27M+ DIPG received 1e6 GD2-CAR T-cells/kg IV on study. One patient with spinal DMG enrolled but became ineligible after manufacturing and was treated on an eIND at DL1. An Ommaya reservoir was placed in all subjects for therapeutic monitoring of intracranial pressure. Subjects underwent lymphodepletion with fludarabine/cyclophosphamide and remained inpatient for at least two weeks post-infusion. Results All subjects developed cytokine release syndrome (Grade 1–3) manifested by fever, tachycardia and hypotension. Other toxicities included ICANS (Grade 1–2) and neurological symptoms/signs mediated by intratumoral inflammation which we have termed Tumor Inflammation-Associated Neurotoxicity (TIAN). No evidence of on-target, off-tumor toxicity was observed in any patients. No dose-limiting toxicities occurred. CAR T cells trafficked to the CNS and were detected in CSF and blood. 3/4 patients exhibited marked improvement or resolution of neurological deficits and radiographic improvement. The patient treated on an eIND exhibited &amp;gt;90% reduction in spinal DMG volume but progressed by month 3. Re-treatment of this subject via intracerebroventricular administration resulted in a second reduction in spinal DMG volume by ~80%. Conclusions GD2-CAR T-cells at DL1 demonstrate a tolerable safety profile in patients with H3K27M+ DIPG/DMG with clear signs of T-cell expansion and activity including clinical responses.
Medicalized Hotel as an Alternative to Hospital Care for Management of Noncritical COVID-19
Authors: Orla Torrallardona-Murphy, Juan M. Pericàs, Neus Rabaneda-Lombarte, Marta Cubedo, David Cucchiari, Júlia Calvo, Júlia Serralabós, Elisenda Alvés, Aleix Agelet, Judit Hidalgo, Eduarda Alves, Laura García, Marta Sala, Irene Pereta, Eva Castells, Adolfo Suárez, Anna Carbonell, Nuria Seijas, Faust Feu, Antonio Alcaraz, Carme Hernández, Emmanuel Coloma, David Nicolás
Journal: Annals of Internal Medicine (2021)

Medicalized Hotel as an Alternative
Health-related quality of life in the treatment and survivorship phases of breast cancer.
Authors: Manraj Kaur, Anne Klassen, Feng Xie, Charlene Rae, Andrea Pusic
Journal: Journal of Clinical Oncology (2021)

e18621 Background: Understanding the health-related quality of life (HRQOL) of breast cancer during treatment and survivorship is important; however, little data are available - particularly for long-term ( &gt; 5 year) survivors. Health utility scores anchored between 0 (death) and 1 (perfect/best possible health) have been shown to be a good proxy index score of the overall HRQOL. The aim of this study was to estimate the utilities in the treatment and survivorship of breast cancer using validated preference-based measures(PBMs). Methods: Women (18 years or older) with history of breast cancer (on/off treatment) were recruited via Love Research Army (LRA), an online community of women engaged in breast cancer research. Members of the LRA were invited to participate via email and women who self-selected to be eligible were asked to complete clinical and demographics form and two generic PBMs - EQ-5D and Short Form-12 (SF-12), and one cancer-specific PBM-European Organization for Research and Treatment of Cancer-8D (EORTC-8D). Descriptive statistics and non-parametric analysis of variance tests were used to examine differences between the survivorship groups. Results: 1,636 women aged 46 ± 10 years were included in the analysis. Mean age at primary diagnosis was 35 ± 10 years and most patients were diagnosed with breast cancer stage 0-2 (n = 1362, 83.25%). For women currently on treatments, mean utility values were: chemotherapy (EQ-5D = 0.61, SF-6D = 0.67,EORTC-8D = 0.69), radiation(EQ-5D = 0.71, SF-6D = 0.67, EORTC-8D = 0.66), hormone replacement therapy (EQ-5D = 0.82,SF-6D = 0.76,EORTC-8D = 0.85), targeted therapy (EQ-5D = 0.77, SF-6D = 0.74, EORTC-8D = 0.82), and surgery (EQ-5D = 0.81,SF-6D = 0.69, EORTC-8D = 0.78). For women diagnosed with arm lymphedema (n = 182,11%), utility values were EQ-5D = 0.79,SF-6D = 0.74, EORTC-8D = 0.82. Women who were ≤ 5 years post-primary diagnosis reported slightly lower utility values (EQ-5D = 0.82,SF-6D = 0.76,EORTC-8D = 0.84) than women who were 6-10 years (EQ-5D = 0.83,SF-6D = 0.76,EORTC-8D = 0.85; p = 0.117) post-primary diagnosis. However, when utilities for women who were ≤ 5 years post-primary diagnosis were compared to women who were 11 to 15 years (EQ-5D = 0.86,SF-6D = 0.79,EORTC-8D = 0.88) and over 15 years (EQ-5D = 0.86,SF-6D = 0.81,EORTC-8D = 0.89) post-primary diagnosis, the difference was statistically significant (p = 0.000). Women who belonged to non-White ethnic groups, had lower levels of education (Bachelors or less) and reported less than USD 50,000 annual income in the previous year reported lower utility values across all time points, after adjusting for age and cancer stage. Conclusions: This study shows that the HRQOL decline in the first five years post-primary breast cancer diagnosis persists for several years into survivorship. Further, women from ethnic minority groups and lower socioeconomic background have lower HRQOL, irrespective of their age and cancer stage.
Disparities in cardiovascular risk factors by race/ethnicity among adult survivors of childhood cancer: A report from the Childhood Cancer Survivorship Study (CCSS).
Authors: David H Noyd, Yutaka Yasui, Nan Li, Eric Jessen Chow, Smita Bhatia, Andrew Landstrom, Susan Gilchrist, Emily S. Tonorezos, Leah L. Zullig, Jacqueline N. Casillas, Amy Madelon Berkman, Kirsten K. Ness, Daniel A. Mulrooney, Wendy M. Leisenring, Carrie R. Howell, Jamie Michelle Shoag, Anne C. Kirchhoff, Rebecca M. Howell, Gregory T. Armstrong, Kevin C. Oeffinger
Journal: Journal of Clinical Oncology (2021)

10017 Background: Racial, ethnic, and socioeconomic disparities are documented in outcomes for childhood cancer survivors. Understanding whether childhood cancer modifies established disparities in cardiovascular risk factors (CVRFs) in the general population would inform strategies to reduce health inequities among survivors. Methods: The CCSS is a retrospectively constructed cohort with prospective follow-up consisting of 25,579 five year survivors of childhood cancer diagnosed between 1970 and 1999. We estimated the incidence of self-reported Common Terminology Criteria for Adverse Events (CTCAE) grade &gt;2 CVRFs (hypertension, diabetes, dyslipidemia, and obesity) and multiple (&gt;2) CVRFs among survivors. Multivariable Poisson regression estimated the rate ratios (RR) of CVRFs by race/ethnicity, adjusted for key treatment exposures and sociodemographics. Results: Within the CCSS cohort, there were 20,416 non-Hispanic White (NHW), 1625 non-Hispanic Black (NHB), and 2043 Hispanic survivors with the cumulative incidence estimates of each CVRF at age 40 displayed in Table. Survivors who self-reported “Other” or mixed race were excluded for this analysis (n=1495). NHB survivors were more likely to report hypertension (unadjusted RR 1.3; 95% Confidence Interval [CI] 1.0-1.6), diabetes (RR 1.6; 95% CI 1.0-2.4), obesity (RR 1.6; 95% CI 1.4-1.9), and multiple CVRF (RR 1.3; 95% CI 1.2-1.5), whereas Hispanic survivors were more likely to report diabetes (RR 1.7; 95% CI 1.2-2.4), obesity (RR 1.4; 95% CI 1.2-1.5), and multiple CVRFs (RR 1.1; 95% CI 1.0-1.3) compared with NHW survivors. These observed disparities in risks of CVRFs remained nearly unchanged even after adjustment for sociodemographic factors (age, sex, household income, education, marital status, employment, and insurance) and treatment exposures (Yes/No for anthracyclines, alkylators, and chest radiation). Conclusions: NHB and Hispanic adult survivors demonstrate a higher burden of CVRF compared with NHW survivors, particularly diabetes and obesity. The associated morbidity of these conditions and established increase they incur in risk of more severe cardiovascular disease emphasizes the need for interventions to mitigate CVRFs to promote health equity among these survivors.[Table: see text]
Biomarker tissue journey among patients (pts) with untreated metastatic non-small cell lung cancer (mNSCLC) in the U.S. Oncology Network community practices.
Authors: Nicholas J. Robert, Esmond D. Nwokeji, Janet L. Espirito, Liwei Chen, Mandar Karhade, Makenzi Colleen Evangelist, Alexander I. Spira, Marcus A. Neubauer, Susie A. Bullock, Robert L. Coleman
Journal: Journal of Clinical Oncology (2021)

9004 Background: Given the importance of molecular testing and targeted therapy for mNSCLC, the MYLUNG (Molecularly Informed Lung Cancer Treatment in a Community Cancer Network) consortium pragmatic study assessed real-world biomarker testing rates and turnaround times (TAT) within The US Oncology Network of over 1,000 providers across the United States. Methods: This was a retrospective observational chart review study of pts with mNSCLC initiating first-line (1L) systemic therapy between 04/01/2018 and 03/31/2020. iKnowMed electronic health records were used to examine timing of biomarker testing: before 1L therapy (cohort 1), after 1L therapy (cohort 2) or no testing (cohort 3). We assessed testing rates for ALK, BRAF, EGFR, ROS1, and PD-L1; use of full next-generation sequencing panel (NGS); time from mNSCLC diagnosis (dx) to 1L therapy; TAT from biomarker orders to results; and time from mNSCLC dx to test results. Results: We identified 3474 adults. Median age was 69 years (range 23-90), 51% female, 74% with adenocarcinoma and 76% with a documented ECOG performance status of 0 or 1. Testing rates are shown in table: 90% of pts had at least one biomarker test and 46% received all 5 biomarker tests. Changes in testing rates from 2018 to 2020 were 51% to 59% for BRAF, 71% to 71% for EGFR, 71% to 70% for ALK, 69% to 67% for ROS1, 82% to 84% for PD-L1, and 42% to 49% for pts tested for all 5 biomarkers. NGS testing increased from 33% to 44% (p&lt;0.0001). The median (interquartile range [IQR]) time from mNSCLC dx to 1L therapy for all pts was 35 (22, 55) days. Median (IQR) TAT from biomarker testing orders to results ranged from 10 (6, 17) to 15 (10, 22) days for the individual biomarkers; and time from mNSCLC dx to biomarker results ranged from 14 (7, 26) to 21 (12, 36) days by biomarker. Conclusions: This real-world study showed that most pts received at least one biomarker test prior to 1L, but &lt;50% received all 5 tests. NGS testing occurred in &lt;50% of pts but increased over the periods examined. Median time from dx to 1L therapy was about 5 weeks and TAT from orders to results about 2 weeks. Analyses by histology and other trends will be reported. These data will be compared to the next phase of the MYLUNG study, which will evaluate contemporary ordering practices and TATs prospectively[Table: see text]
Generation of triacyl lipopeptide-modified glycoproteins by metabolic glycoengineering as the neoantigen to boost anti-tumor immune response
Authors: Yujia Zhao, Siyu Li, Jianying Lv, Yonghui Liu, Yanan Chen, Yanhua Liu, Xiaosu Chen, Jia Li, Xuan Qin, Xiaoshuang Wang, Jie Shi, Yi Shi, Rong Xiang
Journal: Theranostics (2021)

The lack of tumor specific antigens (TSA) and the immune tolerance are two major obstacles for the immunotherapy of cancer. Current immune checkpoint inhibitors (ICIs) show clinical responses in only limited subsets of cancer patients, which, to some extent, depends on the mutation load of tumor cells that may generate neoantigens. Here, we aimed to generate a neoantigen MDP to exhibit stronger anti-tumor efficacy. Methods: In this study, we utilized chemically modified sialic acid precursor tetra acetyl-N-azidoacetyl-mannosamine (AC4ManNAZ) to engineer the glycoproteins on the membranes of tumor cells for the covalent ligation of hapten adjuvant Pam3CSK4 in vivo, which eventually generated a neoantigen, i.e., ManNAZ-DBCO-Pam3CSK4 (MDP), on tumor cells. The high labeling efficiency, relatively specific biodistribution in tumor tissues and the anti-tumor efficacy were confirmed in the syngeneic murine models of the breast cancer and the lung cancer. Results: The generation of MDP neoantigen in tumor-bearing mice significantly evoked both the humoral and the T-cell-dependent antitumor immune responses, resulting in a strong inhibition on the growth of the breast cancer and the lung cancer allografts and significantly prolonged survival of tumor-bearing mice. Interestingly, MDP neoantigen was able to dramatically increase the sensitivity of cancer cells to ICIs and greatly enhance the anti-tumor efficacy in the murine models of both breast cancer and the lung cancer, which showed no or low responses to the immunotherapy with anti-PD1 antibody alone. Conclusions: We developed a simple metabolic glycoengineering method to artificially generate neoantigens on tumor cells to enhance tumor cell immunogenicity, which is able to significantly improve the response and the clinical outcome of ICIs.
Exploring the degradation behavior of MgXAg alloys by in vitro electrochemical methods
Authors: Yuqiuhan Zhang, Tycho Zimmermann, Wolf-Dieter Mueller, Frank Witte, Florian Beuer, Andreas Schwitalla
Journal: Bioactive Materials (2021)

Magnesium as biodegradable biomaterial could serve as bone augmentation material in implant dentistry. The knowledge about the predictability of the biodegradation process is essential as this process needs to go hand in hand with the formation of new bone to gradually replace the augmentation material. Therefore, this work aimed to assess if the electrochemistry (EC) measurements of the corrosion process correlate with the surface features at various time points during the surface degradation, in order to describe the degradation process of Mg and Mg alloys more reliably, under the assumption that differences in EC behavior can be detected and related to specific patterns on the surface. In this test setup, a special optical chamber was used for electrochemical measurements on Mg and Mg-alloys (Mg2Ag, Mg4Ag, and Mg6Ag). Specimens were investigated using different circulating cell culture solutions as electrolytes, these were minimum essential medium (MEM), Hank's Balanced Salt Solution (HBSS), and MEM+ (MEM with added sodium hydrogen carbonate) at 37 °C. Open circuit potential measurements (OCP) over 30 min followed by cyclic polarization were performed. The electrochemistry data, including OCP, exchange current density and corrosion potential, were compared with visible changes at the surface during these treatments over time. The results show that the addition of silver (Ag) leads to a "standardization" of the degradation regardless of the selected test medium. It is currently difficult to correlate the visible microscopic changes with the data taken from the measurements. Therefore, further investigations are necessary.
Holding Iron Measurement to a Gold Standard: Comparing Reticulocyte Hemoglobin Content to Traditional Biomarkers in Predicting Response to Intravenous Iron Supplementation in Hemodialysis Patients
Authors: Justin Chau, Kantima Phisitkul, Patrick Ten Eyck, Chaorong Wu, Mony Fraer, Usha Perepu
Journal: Blood (2017)