tbuckley/cabot-search huggingface dataset:
Abstract 408: Quantification of cell surface HLA-A2 and intracellular Survivin protein levels for tumor blasts and non-blast immune cells in multiple myeloma bone marrow aspirates using a rapid sample preservation methodology followed by 10-color FACS assay
Authors: Tejaswini Hardas, Hyun-Jeong Ra, James Sheridan, Maria Kovalenko, Catherine Tribouley
Journal: Cancer Research (2021)

Abstract Introduction: Multiple myeloma (MM) is a plasma cell disorder characterized by clonal expansion and accumulation of immature undifferentiated neoplastic cells in the bone marrow (BM). Recent advances in fluorochrome chemistries, flow cytometry (FACS) instrumentation and rapid tissue preservation methodologies have created opportunities for broader adoption of FACS in the clinical management of multiple myeloma patients. Methods: We have developed a 10 color, 2 tube FACS assay based on recommendations made by the European Myeloma Network for phenotyping plasma cell gammopathies to identify abnormal blasts in multiple myeloma patient bone marrow aspirates. The assay includes essential plasma cell markers CD138, CD38, CD56 and CD19 to differentiate abnormal blasts from reactive plasma cells. Use of a multi epitope fluorochrome conjugated anti-CD38 antibody enables CD38 detection in patients on anti-CD38 therapy. Results: Quantification of cell surface HLA-A2 and intracellular survivin protein was made possible using fluorochrome conjugated antibodies in combination with bead standards. The SmartTube™ proteomic stabilizer system for rapid preservation was used to freeze BM aspirate specimens for later analysis at locations with appropriate FACS equipment and trained staff. Consistent with previously published literature, patient survivin levels were elevated on abnormal MM blasts in comparison to survivin levels on non-blast immune cells. Conclusion: We have developed a robust FACS methodology that would be easy to implement in the clinical trial and development setting with minimal training. The assay can consistently identify abnormal blasts in BM samples of multiple myeloma patients and quantify intracellular and cell surface biomarkers related to MM disease or disease treatment responses. Citation Format: Tejaswini Hardas, Hyun-Jeong Ra, James Sheridan, Maria Kovalenko, Catherine Tribouley. Quantification of cell surface HLA-A2 and intracellular Survivin protein levels for tumor blasts and non-blast immune cells in multiple myeloma bone marrow aspirates using a rapid sample preservation methodology followed by 10-color FACS assay [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 408.
Abstract PL06-03: Exploiting genome instability for new cancer therapies: PARP inhibitors and beyond
Authors: Stephen P. Jackson
Journal: Cancer Research (2021)

Abstract As DNA is frequently subject to a wide array of molecularly distinct forms of damage, life has evolved multiple DNA repair and associated processes, collectively termed the DNA-damage response (DDR). The importance of DNA repair and other DDR mechanisms is underlined by their deregulation or loss causing cancer and various human genetic disorders. Work in my laboratory aims to decipher DDR mechanisms, particularly those triggered by DNA double-strand breaks. In my talk, I will begin by briefly summarising past work by me and my collaborators that led to the world's first registered DDR enzyme inhibitor drug - the PARP inhibitor olaparib/Lynparza. I will then describe some of our recent work using CRISPR-Cas9 genetic screens to discover new DDR factors/regulators, identify potential new avenues for anti-cancer therapy, and help us understand how cancer cells can evolve resistance to DNA-damaging chemotherapies, PARP inhibitors or other DDR enzyme inhibitors. Citation Format: Stephen P. Jackson. Exploiting genome instability for new cancer therapies: PARP inhibitors and beyond [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr PL06-03.
Abstract 3003: In vitro and in vivo model for evaluation of novel therapeutic agents in patient -derived acute B-lymphoblastic leukemia (B-ALL)
Authors: Bandana Ajay Vishwakarma, Bhavna Verma, Amy Wesa
Journal: Cancer Research (2021)

Abstract B-cell Acute Lymphoblastic Leukemia is a hematological malignancy with malignant transformation and proliferation of B-Cell progenitors. Young patients fare well with common therapeutic agents and hematopoietic stem cell transplant, but a subpopulation is chemo-resistant and has high relapse rate. Besides, prognosis in adult patient is worse than younger individuals. Thus, there is an increase need for development of novel and targeted therapeutics. Lack of suitable in vitro culture conditions for primary B-ALL cells severely impairs the evaluation of new therapeutics. We have established a short-term culture system that supports survival of primary B-ALL cells ex vivo for screening of candidate therapeutic agents. Different culture conditions were evaluated, and cell growth/viability was assessed using Cell titer-Glo assay. Out of 13 primary B-ALL models studied 5 models proliferated and 5 remain stable and viable till day 3. Flow cytometry study showed that all the models stably expressed CD19 and CD20 throughout the assay. The models were tested for sensitivity to chemotherapeutic drugs doxorubicin, vincristine, imatinib and cytarabine. Heterogeneous dose dependent responses were observed across the models (IC50 17nM - 0.3 µM doxorubicin), (IC50 3 - 79 nM vincristine) indicating a range of relative sensitivity to B-ALL models. Interestingly, BCR-ABL-ve models were resistant to imatinib and BCR-ABL+ve sensitive. Next ,to develop patient derived xenograft preclinical B-ALL model, two million PBMC from B-ALL patients (n=14) were intravenously transplanted into sub-lethally irradiated NCG mice. 100% engraftment(n=5,P1) was observed in all the models, but latency of engraftment(&amp;gt;3%) in peripheral blood varied from 15 days to 3.5 months. The time of passage varied from 40 to 120 days. Flow cytometry analyses showed 30-95% of the bone marrow cells was hCD45+, hCD19+ cells. Splenomegaly was observed and infiltration of 40-98% of B-ALL cells was detected in spleen. Engrafted cells matched the immunophenotype of the corresponding patient. On serial transplantation (n=15) these models showed similar engraftment and immunophenotype. Thus, at Champions we have established a robust in vitro platform for screening new drugs for B-ALL and a passagable patient derived preclinical xenograft model for in vivo drug efficacy study. Citation Format: Bandana Ajay Vishwakarma, Bhavna Verma, Amy Wesa. In vitro and in vivo model for evaluation of novel therapeutic agents in patient -derived acute B-lymphoblastic leukemia (B-ALL) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3003.
Go with the flow? High flow nasal cannula for bronchoscopy
Authors: Prema Nanavaty, David J Feller-Kopman
Journal: Thorax (2021)

<h3>Introduction</h3> Growing numbers of public access defibrillators aim to improve the effectiveness of bystander cardiopulmonary resuscitation prior to ambulance arrival. In the UK, however, public access defibrillators are only deployed successfully in 1.7% of out-of-hospital cardiac arrests. We aimed to understand whether this was due to a lack of devices, lack of awareness of their location or a reflection of lack of public knowledge and confidence to use a defibrillator. <h3>Methods</h3> Face-to-face semistructured open quantitative questionnaire delivered in a busy urban shopping centre, to identify public knowledge relating to public access defibrillation. <h3>Results</h3> 1004 members of the public aged 9–90 years completed the survey. 61.1% had been first aid trained to a basic life support level. 69.3% claimed to know what an automatic external defibrillator was and 26.1% reported knowing how to use one. Only 5.1% knew where or how to find their nearest public access defibrillator. Only 3.3% of people would attempt to locate a defibrillator in a cardiac arrest situation, and even fewer (2.1%) would actually retrieve and use the device. <h3>Conclusions</h3> These findings suggest that a lack of public knowledge, confidence in using a defibrillator and the inability to locate a nearby device may be more important than a lack of defibrillators themselves. Underused public access defibrillation is a missed opportunity to save lives, and improving this link in the chain of survival may require these issues to be addressed ahead of investing more funds in actual defibrillator installation.
Abstract 434: Characterizing viral mRNA and immuno-protein expression in head and neck squamous cell carcinoma using a novel automated RNAscope™/Polaris™ integrated assay
Authors: Sara Pollan, Arezoo Hanifi, Mate Nagy, Nicholas Stavrou, Erinn Parnell, Maricel Gozo, Nickolas Attanasio, Josette William, Qingyan Au
Journal: Cancer Research (2021)

Abstract Background: Chronic viral infection can generate inflammatory microenvironments leading to neoplastic growth and cancer development. Cancer patients with chronic viral infection have been shown to exhibit worse outcomes compared to non-infected individuals. One such cohort, head and neck squamous cell carcinoma (HNSCC) patients infected with chronic human cytomegalovirus (CMV), have increased risk of death when receiving radiotherapy or radiochemotherapy. This is clinically significant as HNSCC already carries a high mortality rate and low response to surgery and chemotherapeutic treatment. The ability to detect and localize viral infection and immune response in the same patient tissues has been historically under-developed and may assist in stratifying patients for therapeutic intervention. Methods: Immune infiltrate to tumor in CMV infected and non-infected samples was assessed in HNSCC patient tissue using RNAscope in-situ hybridization (ISH) probe to detect CMV mRNA and Vectra® Polaris™ automated multiplex protein detection of CD8, PD-L1, CD68 and panCK with OPAL dyes. Results: We developed a novel automated RNAscope™/Vectra® Polaris™ integrated multiplex immunofluorescence (IF) assay with OPAL detection and quantification of signal using Indica HALO® algorithms. The results include quantitative and reproducible RNAscope fluorescent ISH counting, cell-by-cell expression profiles, multiplex protein quantification and whole-slide image analysis. Conclusion: NeoGenomics Laboratories RNAscope™/Polaris™ integrated assay detects and quantifies CMV viral infection and protein expression of PD-L1 positive and negative cytotoxic T cells and macrophages within and adjacent to HNSCC tumor regions. Citation Format: Sara Pollan, Arezoo Hanifi, Mate Nagy, Nicholas Stavrou, Erinn Parnell, Maricel Gozo, Nickolas Attanasio, Josette William, Qingyan Au. Characterizing viral mRNA and immuno-protein expression in head and neck squamous cell carcinoma using a novel automated RNAscope™/Polaris™ integrated assay [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 434.
Head-to-head comparison of orostate cancer detection rate at MRI-targeted FUSION biopsy between hub and spoke mpMRI Italian centers
Authors: M. Droghetti, L Bianchi, G. Lando, C. Roveroni, M. Salvador, C. Beretta, E. Balestrazzi, A. Feruzzi, G. Milani, F. Chessa, A. Rustici, A. De Cinque, B. Corcioni, C. Gaudiano, R. Golfieri, R. Schiavina, E. Brunocilla
Journal: European Urology (2021)
Epigenetic priming of Bladder cancer cells improves CAR T-cell cytotoxicity
Authors: C.M. Grunewald, C. Haist, C. König, P. Petzsch, E. Nößner, C. Wiek, K. Scheckenbach, K. Köhrer, G. Niegisch, H. Hanenberg, M.J. Hoffmann
Journal: European Urology (2021)
Abstract 1604: Anticancer nanocage platforms for combined immunotherapy designed to harness immune checkpoints and deliver anticancer drugs
Authors: Soyoun Kim, Minseong Kim
Journal: Cancer Research (2021)

Abstract The interaction of programmed cell death 1 ligand 1 (PD-L1) with its receptor, programmed cell death 1 (PD-1), inhibits T-cell responses. Monoclonal antibodies that block this interaction have been shown effective as immunotherapy. However, only a subset of cancers exhibits a durable response to PD-1/PD-L1 blockade. Moreover, antibody-based immune checkpoint blockade is costly and is occasionally accompanied by systemic side effects. To overcome these limitations of antibody-based immune checkpoint blockade, an immune checkpoint-blocking ferritin nanocage displaying 24 PD-L1 binding peptides (PD-L1pep1) on its surface was designed and constructed. These ferritin nanocages displaying PD-L1pep1 (PpNF) specifically bind to PD-L1 expressed on cancer cells or to purified PD-L1 with a ~30 nM binding affinity. The addition of PpNF to cocultures of T cells and cancer cells inhibited PD-1/PD-L1 interactions and restored T-cell activities. In a mouse model of syngeneic colon cancer, PpNF specifically targeted tumors and showed antitumor activity. Moreover, PpNF nanocages encapsulating the chemotherapeutic drug doxorubicin had more potent antitumor activity than a monoclonal antibody against PD-L1. These results demonstrate that ferritin nanocages displaying surface PD-L1pep1 can be efficiently applied for immunotherapy, especially when encapsulating small chemotherapeutic drugs. These nanocages may have promise as an immunotherapeutic nanomedicine against various solid tumors. Citation Format: Soyoun Kim, Minseong Kim. Anticancer nanocage platforms for combined immunotherapy designed to harness immune checkpoints and deliver anticancer drugs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1604.
How Cancer Risk SNPs May Contribute to Prostate Cancer Disparities
Authors: Mnaya Y. Mavura, Franklin W. Huang
Journal: Cancer Research (2021)

Abstract Disparities in cancer incidence, prevalence, burden, and outcome exist among specific population groups in the United States. Researchers have identified germline genetic risk single-nucleotide polymorphisms (SNP) that differ by ancestry and may contribute to some of these differences. In this issue of Cancer Research, Han and colleagues found the prostate cancer risk SNP rs4713266 is associated with increased risk of patients with African ancestry. The authors investigated the functional role of the risk SNP, finding that it alters activity of a NEDD9 enhancer and increases NEDD9 expression. The study provides epidemiologic and mechanistic insight into factors that may drive prostate cancer disparities. See related article by Han et al., p. 3766
Performance of Multiparametric Functional Imaging to Assess Peritoneal Tumor Burden in Ovarian Cancer
Authors: Estelle Mallet, Martina Aida Angeles, Bastien Cabarrou, David Chardin, Philippe Viau, Mélanie Frigenza, Anne Sophie Navarro, Anne Ducassou, Sarah Betrian, Carlos Martínez-Gómez, Yann Tanguy Le Gac, Elodie Chantalat, Stéphanie Motton, Gwénaël Ferron, Emanuel Barranger, Erwan Gabiache, Alejandra Martinez
Journal: Clinical Nuclear Medicine (2021)

The aim of the study was to evaluate the clinical utility of pretreatment 18F-FDG PET/CT with quantitative evaluation of peritoneal metabolic cartography in relation to staging laparoscopy for ovarian carcinomatosis.A retrospective review of prospectively collected data from 84 patients with FIGO (International Federation of Gynecology and Obstetrics) stage IIIC to IV ovarian cancer was carried out. All patients had a double-blinded 18F-FDG PET/CT review. Discriminant capacity of metabolic parameters to identify peritoneal carcinomatosis in the 13 abdominal regions according to the peritoneal cancer index was estimated with area under the receiver operating characteristic curve (AUC).The metabolic parameter showing the best trade-off between sensitivity and specificity to predict peritoneal extension compared with peritoneal cancer index score was the metabolic tumor volume (MTV), with a Spearman ρ equal to 0.380 (P < 0.001). The AUC of MTV to diagnose peritoneal involvement in the upper abdomen (regions 1, 2, and 3) ranged from 0.740 to 0.765. MTV AUC values were lower in the small bowel regions (9-12), ranging from 0.591 to 0.681, and decreased to 0.487 in the pelvic region 6. 18F-FDG PET/CT also improved the detection of extra-abdominal disease, upstaging 35 patients (41.6%) from stage IIIC to IV compared with CT alone and leading to treatment modification in more than one third of patients.18F-FDG PET/CT metrics are highly accurate to reflect peritoneal tumor burden, with variable diagnostic value depending on the anatomic region. MTV is the most representative metabolic parameter to assess peritoneal tumor extension.
Abstract 2951: Anti-GCGR <i>in vivo</i> efficacy evaluated in a novel humanized B-hGCGR mouse model
Authors: Rufeng Zhang, Chengzhang Shang, Yuting Hu, Veronika Chromikova, Qingcong Lin
Journal: Cancer Research (2021)

Abstract GCGR (glucagon receptor) is a G-protein-coupled seven-transmembrane protein, a typical representative of the class B GPCR family. Animals homozygous for a targeted mutation in this gene exhibit reduced blood glucose levels, increased plasma glucagon and amino acid levels associated with alpha-cell hyperplasia. Glucagon activates intracellular adenylate cyclase by specifically binding to GCGR on the surface of target cells in the liver. This results in an increase in intracellular cAMP levels, playing a role in promoting glycogenolysis and gluconeogenesis, and promoting blood glucose elevation. The crucial role in regulation of blood glucose levels and glucose homeostasis is posing GCGR as a potential drug target for type 2 diabetes and related diseases. Currently, much attention and many resources are directed towards research and development of antibody drugs targeting the glucagon receptor. Joining these efforts, Biocytogen has developed a GCGR humanized mouse model (B-hGCGR mouse). Human GCGR protein and mRNA were detected in liver tissue of homozygous B-hGCGR mice, but not in wild type mice. Physiological indexes have been analyzed. Results indicated that the random blood glucose, fasting blood glucose, and glucose tolerance were comparable to the wild type mice. In addition, we characterized the ability of glucagon to stimulate production of cAMP. We observed that glucagon elicits a dose specific increase of cAMP in membranes prepared from the humanized GCGR mice comparable to the cAMP levels observed in membranes prepared from wild type mice. In pharmacodynamic experiments using B-hGCGR mice we showed that an anti-GCGR antibody (Crotedumab) was able to effectively reduce random blood glucose and fasting blood glucose levels and improve the glucose tolerance, validating our humanized mouse model. This antibody also blocked the functional response to glucagon in B-hGCGR mice more efficiently than what can be observed in an approach targeting the wild type murine receptor using antagonists. These data demonstrate that B-hGCGR mice are a promising model for preclinical in vivo pharmacodynamic assessment of anti-GCGR antibodies. Citation Format: Rufeng Zhang, Chengzhang Shang, Yuting Hu, Veronika Chromikova, Qingcong Lin. Anti-GCGR in vivo efficacy evaluated in a novel humanized B-hGCGR mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2951.
Rare conditions in paediatric patients: New chapter in 2021 EAU Paediatric Urology guidelines
Authors: N.R. Bhatt, R. Nijman, Y.F. Rawashdeh, L.A. ’T Hoen, C. Radmayr, H.S. Dogan, J. Quaedackers, M. Silay, S. Tekgul, R. Stein, G. Bogaert
Journal: European Urology (2021)
RKI-1447は,乳癌における抗浸潤および抗腫瘍活性を有するRho関連ROCKキナーゼの強力な阻害剤である
Authors: A Patel Ronil, D Forinash Kara, Pireddu Roberta, Sun Ying, Sun Nan, P Martin Mathew, Schoenbrunn Ernst, J Lawrence Nicholas, M Sebti Said
Journal: Cancer Research (2012)
Trends in Diversity and Representativeness of Health Care Workers in the United States, 2000 to 2019
Authors: Dan P. Ly, Anupam B. Jena
Journal: JAMA Network Open (2021)

ResultsOur study included 1 648 924 individuals (1 303 496 [79.1%] women; 345 428 [20.9%] men) across 6 health care occupations (Table 1).The percentage of White men in relatively more remunerative occupations (ie, physicians and surgeons, pharmacists, and dentists) decreased between 2000 to 2004 and 2015 to 2019.For example, the percentage of physicians and surgeons who were White men decreased from 54.1% (95% CI, 53.3% to 54.9%) to 43.8% (95% CI, 43.3% to 44.3%)
Abstract 2329: ONC212-induced impairment of oxidative phosphorylation is synergistic with glycolysis inhibition in treatment of pancreatic cancer in vitro and in vivo
Authors: Anna Donovan Louie, Isacco Ferrarini, Lanlan Zhou, Wafik S. El-Deiry
Journal: Cancer Research (2021)

Abstract ONC212 is a fluorinated imipridone shown to have preclinical efficacy against multiple cancers, including pancreatic cancer. One of the binding targets of ONC212 is the mitochondrial peptidase, ClpP, but its role in the anticancer activity of ONC212 is incompletely understood. Understanding the effects of ONC212 on the bioenergetics of pancreatic cancer could facilitate understanding and amplification of its anti-tumor effects. On extracellular flux analysis, ONC212 impairs mitochondrial ATP production and oxidative phosphorylation in multiple pancreatic cancer lines. However, pancreatic adenocarcinoma uses both glycolysis and mitochondrial function to meet its energy demands. Some pancreatic cancer cell lines are resistant to ONC212 inhibition of oxidative phosphorylation alone, but co-treatment with glycolytic inhibitor 2-deoxy-D-glucose (2-DG) synergizes with ONC212 and increases tumor cell death in vitro. Suppression of ClpX, the regulatory binding protein of ClpP, occurs with ONC212 treatment and was used as a biomarker of ONC212 activity. This suppression was demonstrated in multiple pancreatic cancer lines in vitro and in vivo. In a xenograft mouse tumor model of pancreatic cancer using both the ONC212 resistant Bxpc3 pancreatic cancer cell line and the more sensitive HPAF-II cell line, the combination of ONC212 and 2-DG treatment significantly decreased tumor growth and reduced the intertumoral variability. Immunohistochemistry also revealed increased apoptotic markers in these tumors. There was no significant toxicity from dual treatment in mice, which suggests that tumor energy deprivation from dual inhibition of oxidative phosphorylation and glycolysis via ONC212 and 2-DG has a therapeutic window and should be explored further as a potential combination therapy. In addition, if this effect holds true across other models and cancer types, baseline mitoATP percentage could be used as a functional biomarker of sensitivity to ONC212. Citation Format: Anna Donovan Louie, Isacco Ferrarini, Lanlan Zhou, Wafik S. El-Deiry. ONC212-induced impairment of oxidative phosphorylation is synergistic with glycolysis inhibition in treatment of pancreatic cancer in vitro and in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2329.