tbuckley/cabot-search huggingface dataset:
Abstract 1322: Evaluating intracellular accumulation profiles of chemotherapeutic agents using CLENs for the treatment of Y79 retinoblastoma
Authors: Nan Luo, Virali Patel, Minesh Patel, Eric Conte, Robert Campbell
Journal: Cancer Research (2021)

Abstract Retinoblastoma is the most common intraocular malignancy in children, with approximately 200-300 new cases in the United States each year. Currently, conventional chemotherapy agents (carboplatin, cisplatin, doxorubicin, vincristine, and cyclophosphamide) used to treat retinoblastoma, are rapidly eliminated from circulation. Novel lipid nanoparticles (LNP) have been shown to improve delivery of encapsulated chemotherapeutic agents to Y79 retinoblastoma cells, and therefore the agents are less toxic to healthy cells. Past studies have supported the use of LNP delivery systems to enhance chemotherapeutic drug action against Y79 retinoblastoma cells as well. The experimental plan will now evaluate the use of cellular membrane lipid-extracted nanoliposomes (CLENs) to examine targeting using cellular models of retinoblastoma. Y79 cells were cultured in RPMI growth medium supplemented by 20% FBS. CLENs and lipid extracts (LE) were prepared according to previously published protocols. Following the development of Y79-LE nano-preparations consisting of DOPC, Y79-LE, and cholesterol at different ratios, preparations were evaluated in terms of physicochemical properties and uptake by Y79 cells. The additional inclusion of cationic lipid DOTAP in Y79-LE preparations was evaluated for select preparations. Particle sizes and zeta potential values were determined for each preparation type by ZetaPALS. CLENs exhibited an average particle size between 400 to 600 nm. Experiments with Y79-CLENs prepared in the absence and presence of DOTAP, showed they were taken up by the target cell population. In general, the inclusion of Y79-LE increased cellular uptake. The inclusion of cholesterol in combination with DOTAP showed enhanced liposomal uptake in Y79 retinoblastoma cells. Evidence from previous studies suggest a benefit of using lipid nanoparticles compared to more conventional treatment options. Preliminary findings suggest a positive correlation between the particle size and degree of cellular uptake. Additional optimization studies are currently underway. Citation Format: Nan Luo, Virali Patel, Minesh Patel, Eric Conte, Robert Campbell. Evaluating intracellular accumulation profiles of chemotherapeutic agents using CLENs for the treatment of Y79 retinoblastoma [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 1322.
GDF-15中和はマウスおよびヒト以外の霊長類における白金ベース化学療法誘発Emesis,食欲不振および体重減少を軽減する【JST・京大機械翻訳】
Authors: M Breen Danna, Kim Hanna, Bennett Donald, A Calle Roberto, Collins Susie, M Esquejo Ryan, He Tao, Joaquim Stephanie, Joyce Alison, Lambert Matthew, Lin Laura, Pettersen Betty, Qiao Shuxi, Rossulek Michelle, Weber Gregory, Wu Zhidan, B Zhang Bei, J Birnbaum Morris
Journal: Cell Metabolism (2020)
Abstract 2699: Transcriptome analysis identifies molecular markers of tumor-associated high endothelial venules that predict breast cancer survival
Authors: Junko Sawada, Nobuyoshi Hiraoka, Ashley Fournier-Goss, Masanobu Komatsu
Journal: Cancer Research (2021)

Abstract High endothelial venules (HEVs) are specialized post-capillary venules that recruit naïve lymphocytes to the lymph nodes and are essential for the development of adaptive immunity. HEVs can develop in tumors, and these specialized tumor blood vessels are thought to be important for recruiting naïve T cells and B cells into tumors and locally enhance anti-tumor immunity by promoting tertiary lymphoid structure formation. At present, the genes involved in the development and function of tumor-associated HEVs remain largely unknown. By a comparative transcriptome analysis in human breast cancer, we identified the expression of genes that represents the molecular signature of tumor-associated HEVs distinct from the rest of the tumor vasculature. Tumor vessels highly expressing these genes were associated with the accumulation of T and B lymphocytes and the occurrence of tertiary lymphoid structures, which is known to predict therapeutic response to immune checkpoint inhibitor therapies. Moreover, the Cancer Genome Atlas (TCGA) data show that the high expression of these genes is associated with a significant survival benefit in advanced breast cancer. The molecular signature of HEVs identified here may be useful for guiding immunotherapies and provide a new direction for investigating tumor-associated HEVs and their clinical significance. Citation Format: Junko Sawada, Nobuyoshi Hiraoka, Ashley Fournier-Goss, Masanobu Komatsu. Transcriptome analysis identifies molecular markers of tumor-associated high endothelial venules that predict breast cancer survival [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 2699.
Real-life implementation and survival outcomes of geriatric-assessement-based guidelines for treatment decision in older patients with prostate cancer: The ELCAPA-26 cohort study
Authors: A. González Serrano, C. Martinez Tapia, A. De La Taille, P. Mongiat-Artus, J. Irani, A. Bex, E. Paillaud, E. Audureau, T. Barnay, M. Laurent, F. Canouï-Poitrine
Journal: European Urology (2021)
Adverse events related to different antimuscarinics and beta-3-agonist: Analysis of real-life data from Eudra-Vigilance
Authors: C. De Nunzio, A. Nacchia, R. Lombardo, A. Franco, G. Tema, F. Di Giacomo, G. Disabato, L. Rovesti, A. Cicione, A. Tubaro
Journal: European Urology (2021)
Abstract 2313: The characteristics of ERBB2 exon 20 insertion in a large cohort of Chinese NSCLC patients
Authors: Danhua Wang, Hongling Yuan, Honglin Zhu
Journal: Cancer Research (2021)

Abstract Background: ERBB2 mutations, especially exon 20 insertion (ERBB2ex20ins) had been extensively reported in NSCLC as classical driver factors. Previous researches indicate that NSCLC pts with ERBB2ex20ins are drug-resistant to afatinib, gefitinib and erlotinib. Up to now, approvals of targeted therapy of ERBB2ex20ins are still in process. Therefore, the objective of this study is to discover the features of ERBB2ex20ins in Chinese NSCLC patients, which could lead to more effective and personalized diagnosis and treatment. Methods: 20656 Chinese NSCLC cases who had undergone molecular profiling at a Clinical Laboratory Improvement Amendments (CLIA) certified genomics laboratory in China between January 2017 to May 2020 were screened for our study. Some patients' clinical characteristics and treatment history were retrieved from the database for further evaluation. Results: 11492 males and 9134 females were included in our cohort. ERBB2 gene mutation rate was 5.94% (1226/20656). Among them, 290 patients (1.4%), including 114 males and 176 females, harbored with ERBB2ex20ins, which include with p. Tyr772_Ala775dup (84.56%), p.Gly778_Pro780dup (10.74%), p.Ala775_Gly776insLeu(1.01%), p.Ala775_Gly776insVal(1.01%) and others(2.68%). Additionally, ERBB2ex20ins occurred more frequently in female patients (61% vs 39%, p&amp;lt;0.005, fisher exact test), and had a relatively young age (p&amp;lt;0.005, wilcoxon test) compared with others. Moreover co-variations of 290 pts are occurring with EGFR(4, 1.38%), KRAS(3, 1.03%), TP53(156, 53.79%), ERBB2 amp(21, 7.24%), MET amp (2, 0.69%), ALK amp (1, 0.34%) and RET fusion (1, 0.34%). Besides, a relatively lower TMB (p&amp;lt;0.005, wilcoxon test) is shown on the patients with ERBB2ex20ins. We followed up 5 patients with ERBB2ex20ins mutations, who were all insensitive to traditional radiotherapy and chemotherapy and had poor prognosis with short PFS (1.5-12.4 months) and short OS (3.9-13.7 months). Conclusion: Our results showed that the ERBB2ex20ins mutation tended to occur in younger, female patients. Additionally, ERBB2ex20ins mutated samples exhibited lower levels of TMB compared to wildtype tumors, which may not benefit from anti-PD1 treatment. We also found patients with ERBB2ex20ins mutation have been associated with short PFS and short OS. The detail mechanism of resistance and appropriate therapeutic strategies remain to be further study. Citation Format: Danhua Wang, Hongling Yuan, Honglin Zhu. The characteristics of ERBB2 exon 20 insertion in a large cohort of Chinese NSCLC patients [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 2313.
Sputnik V vaccine elicits seroconversion and neutralizing capacity to SARS-CoV-2 after a single dose
Authors: Andres H. Rossi, Diego S. Ojeda, Augusto Varese, Lautaro Sanchez, Maria M. Gonzalez Lopez Ledesma, Ignacio Mazzitelli, Anabel Alvarez Juliá, Santiago Oviedo Rouco, Horacio M. Pallarés, Guadalupe S. Costa Navarro, Natali B. Rasetto, Corina I. Garcia, Shirley D. Wenker, Lila Y. Ramis, Magalí G. Bialer, Maria Jose de Leone, C. Esteban Hernando, Santiago Sosa, Luciana Bianchimano, Antonella S. Rios, Maria Soledad Treffinger Cienfuegos, Julio J. Caramelo, Yesica Longueira, Natalia Laufer, Diego E. Alvarez, Jorge Carradori, Dariana Pedrozza, Alejandra Rima, Cecilia Echegoyen, Regina Ercole, Paula Gelpi, Susana Marchetti, Martín Zubieta, Guillermo Docena, Nicolas Kreplak, Marcelo Yanovsky, Jorge Geffner, Marina Pifano, Andrea V. Gamarnik
Journal: Cell Reports Medicine (2021)

Massive vaccination offers great promise for halting the global COVID-19 pandemic. However, the limited supply and uneven vaccine distribution create an urgent need to optimize vaccination strategies. We evaluate SARS-CoV-2-specific antibody responses after Sputnik V vaccination of healthcare workers in Argentina, measuring IgG anti-spike titers and neutralizing capacity after one and two doses in a cohort of naive or previously infected volunteers. By 21 days after receiving the first dose of the vaccine, 94% of naive participants develop spike-specific IgG antibodies. A single Sputnik V dose elicits higher antibody levels and virus-neutralizing capacity in previously infected individuals than in naive ones receiving the full two-dose schedule. The high seroconversion rate after a single dose in naive participants suggests a benefit of delaying administration of the second dose to increase the number of people vaccinated. The data presented provide information for guiding public health decisions in light of the current global health emergency.
Overcoming Intrinsic Resistance of Cancer Cells to CAR T-Cell Killing
Authors: Jean Lemoine, Marco Ruella, Roch Houot
Journal: Clinical Cancer Research (2021)

In the past few years, chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment for cancers that failed standard treatments. Such therapies have already been approved in several blood cancers, such as B-cell leukemia and lymphoma. Despite this progress, a significant proportion of patients experience primary or secondary resistance to CAR T-cell therapy. Here, we review the mechanisms by which CAR T cells eliminate their target and how cancer cells may be insensitive to such killing (here referred to as intrinsic resistance). Recent studies suggest that the activation of apoptosis through death receptor signaling is responsible for a major part of CAR T-cell cytotoxicity
Abstract 1109: A novel strategy to cope with osimertinib resistance in non-small cell lung cancer by treatment with a PIM kinase inhibitor in combination with a MERTK-selective kinase inhibitor
Authors: Dan Yan, Zikang Tan, Xiaodong Wang, Stephen V. Frye, H. Shelton Earp, Deborah DeRyckere, Douglas K. Graham
Journal: Cancer Research (2021)

Abstract Osimertinib is currently the preferred treatment for EGFR-mutated non-small cell lung cancer (NSCLC) patients due to its superior therapeutic efficacy and prolonged overall survival compared to earlier generation EGFR tyrosine kinase inhibitors, but durable responses to osimertinib treatment are rare due to acquired drug resistance. Thus, there is an urgent need for novel strategies to treat osimertinib-resistant NSCLC. Recently, we found that treatment with MRX-2843, a novel MERTK-selective kinase inhibitor currently in Phase I clinical trials, resulted in dose-dependent inhibition of cell expansion and colony formation in an osimertinib-resistant (osiR) H4006 derivative cell line. An unbiased screen of 378 kinase inhibitors was carried out to identify compounds that synergized with MRX-2843 to inhibit expansion of an osiR derivative of the EGFR-mutated H4011 cell line. Treatment with 1µM PIM kinase inhibitor SGI-1776 or 100nM MRX-2843 alone reduced cell density by 5±3% and 44±7%, respectively, while treatment with MRX-2843 and SGI-1776 combined mediated an 82±0.4% decrease. Synergy was also observed in H4006 osiR and H1650 osiR derivative cell lines. Furthermore, treatment with PIM447, a structurally distinct PIM kinase inhibitor, and MRX-2843 decreased cell expansion more effectively than either agent alone. Mechanistically, treatment with a PIM kinase inhibitor in combination with MRX-2843 decreased downstream PI3K-AKT and MAPK-ERK signaling more effectively than single agents. Additionally, combined treatment with MRX-2843 and SGI-1776 prevented colony formation, while single agents had limited effect. In all, these data indicate that combining MRX-2843 and a PIM TKI may control osimertinib resistant tumor growth, providing a potential treatment strategy for osimertinib resistant EGFR-mutated NSCLC patients for whom the choices are still limited. Citation Format: Dan Yan, Zikang Tan, Xiaodong Wang, Stephen V. Frye, H. Shelton Earp, III, Deborah DeRyckere, Douglas K. Graham. A novel strategy to cope with osimertinib resistance in non-small cell lung cancer by treatment with a PIM kinase inhibitor in combination with a MERTK-selective kinase inhibitor [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 1109.
Latest advances in the management of classical Hodgkin lymphoma: the era of novel therapies
Authors: Razan Mohty, Rémy Dulery, Abdul Hamid Bazarbachi, Malvi Savani, Rama Al Hamed, Ali Bazarbachi, Mohamad Mohty
Journal: Blood Cancer Journal (2021)

Hodgkin lymphoma is a highly curable disease. Although most patients achieve complete response following frontline therapy, key unmet clinical needs remain including relapsed/refractory disease, treatment-related morbidity, impaired quality of life and poor outcome in patients older than 60 years. The incorporation of novel therapies, including check point inhibitors and antibody-drug conjugates, into the frontline setting, sequential approaches, and further individualized treatment intensity may address these needs. We summarize the current treatment options for patients with classical Hodgkin lymphoma from frontline therapy to allogeneic hematopoietic stem cell transplantation and describe novel trials in the field.
Abstract 15532: Relationship Between Baseline PCSK9 and LDL-C Reduction in Response to the Investigational RNAi Therapeutic Inclisiran
Authors: Robert M Stoekenbroek, David Kallend, Peter L Wijngaard, R. Scott Wright, Ulf Landmesser, Lawrence A Leiter, John J Kastelein, Kausik K Ray
Journal: Circulation (2018)

Introduction: The ORION-1 trial demonstrated that dosing with inclisiran, an RNAi therapeutic inhibiting PCSK9 synthesis in the liver, robustly lowers LDL-C. Inhibiting PCSK9 in the circulation wit...
Food strategy calls for tax on sugar and salt and for GPs to prescribe fruit and vegetables
Authors: Gareth Iacobucci
Journal: BMJ (2021)

The government should introduce a £3bn (€3.5bn; $4.2bn) tax on sugar and salt and encourage doctors to prescribe fruit and vegetables as part of a package of reforms to make England a healthier nation, an independent review1 has said.

The National Food Strategy, led by businessman Henry Dimbleby, urges the government to introduce a “world first” £3 a kg tax on sugar and a £6 a kg tax on salt sold for use in processed foods, restaurants, and catering businesses. This would raise up to £3.4bn a year, some of which could be used to extend the provision of free school meals and support …
MiR-144 Targets APP to Regulate AML1/ETO+ Leukemia Cell Migration Via p-ERK/c-Myc/MMP-2 Pathway
Authors: Fanyi Meng, Ling Jiang, Wei Meng, Guo-Pan Yu, Yin Changxin, Zhixiang Wang, Xuejie Jiang, Qifa Liu
Journal: Blood (2017)
Abstract 2425: Prevalence of NTRK fusions and clinico-pathological characteristics of Middle Eastern papillary thyroid cancer revealed enrichment in BRAF wild-type PTC
Authors: Abdul K. Siraj, Rong Bu, Sandeep K. Parvathareddy, Yan Kong, Padmanaban Annaiyappanaidu, Saeeda O. Ahmed, Maha Al-Rasheed, Khawla S. Al-Kuraya
Journal: Cancer Research (2021)

Abstract Fusions involving neurotrophic tyrosine receptor kinase (NTRK) are known oncogenic drivers in a broad range of tumor types. It recently gained attention as predictor of targeted therapy, since selective NTRK inhibitor are now approved in US and Europe for patients with solid tumor harboring gene fusions. However, estimation of NTRK gene fusion/alteration frequency and its clinico-pathological characteristics in papillary thyroid cancer (PTC) is limited, especially in a population with high incidence for PTC like Middle Eastern population. This study aims to characterize the NTRK gene fusion frequency using FISH analysis and investigate the utility of pan-Trk immunohistochemistry as predictor of NTRK fusion in a large cohort of Middle Eastern PTC. FISH analysis for NTRK gene fusions as well as immunohistochemical (IHC) staining was conducted on a cohort of 315 Middle Eastern PTC. Correlation of NTRK with clinico-pathological markers and patient outcome were determined. 6.0% (19/315) patients were identified with NTRK gene fusions and significantly associated with pediatric PTC, lymph node metastasis and BRAF wild-type. Pan-Trk IHC was positive in 9.2% (29/315) and significantly associated with NTRK gene fusion with a sensitivity of 73.7% and specificity of 94.9% in this cohort. In conclusion, this study confirms the presence of NTRK fusions in Middle Eastern PTC and mostly enriched in BRAF wild-type and pediatric age group and propose the usefulness of IHC to screen for PTC patients with NTRK fusion that might benefit from TRK inhibitors. Citation Format: Abdul K. Siraj, Rong Bu, Sandeep K. Parvathareddy, Yan Kong, Padmanaban Annaiyappanaidu, Saeeda O. Ahmed, Maha Al-Rasheed, Khawla S. Al-Kuraya. Prevalence of NTRK fusions and clinico-pathological characteristics of Middle Eastern papillary thyroid cancer revealed enrichment in BRAF wild-type PTC [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 2425.
Multi-omics reveals clinically relevant proliferative drive associated with mTOR-MYC-OXPHOS activity in chronic lymphocytic leukemia
Authors: Junyan Lu, Ester Cannizzaro, Fabienne Meier-Abt, Sebastian Scheinost, Peter-Martin Bruch, Holly A. R. Giles, Almut Lütge, Jennifer Hüllein, Lena Wagner, Brian Giacopelli, Ferran Nadeu, Julio Delgado, Elías Campo, Maurizio Mangolini, Ingo Ringshausen, Martin Böttcher, Dimitrios Mougiakakos, Andrea Jacobs, Bernd Bodenmiller, Sascha Dietrich, Christopher C. Oakes, Thorsten Zenz, Wolfgang Huber
Journal: Nature Cancer (2021)
Challenges and next steps in the advancement of immunotherapy: summary of the 2018 and 2020 National Cancer Institute workshops on cell-based immunotherapy for solid tumors
Authors: Laura K Fogli, Rosemarie Aurigemma, Connie L Sommers, Anju Singh, Kasia Bourcier, Marc S Ernstoff
Journal: Journal for ImmunoTherapy of Cancer (2021)

Cell-based immunotherapies have had remarkable success in the clinic, specifically in the treatment of hematologic malignancies. However, these strategies have had limited efficacy in patients with solid tumors. To better understand the challenges involved, the National Cancer Institute (NCI) convened an initial workshop with immuno-oncology thought leaders in December 2018 and a follow-up workshop in December 2020. The goals of the NCI workshops on cell-based immunotherapy for solid tumors were to discuss the current state of the field of cell-based immunotherapy, obtain insights into critical knowledge gaps, and identify ways in which NCI could facilitate progress. At both meetings, subjects emphasized four main types of challenges in further developing cell-based immunotherapy for patients with solid tumors: scientific, technical, clinical, and regulatory. The scientific barriers include selecting appropriate targets, ensuring adequate trafficking of cell therapy products to tumor sites, overcoming the immunosuppressive tumor microenvironment, and identifying appropriate models for these investigations. While mouse models may provide some useful data, the majority of those that are commonly used are immunodeficient and unable to fully recapitulate the immune response in patients. There is therefore a need for enhanced support of small early-phase human clinical studies, preferably with adaptive trial designs, to provide proof of concept for novel cell therapy approaches. Furthermore, the requirements for manufacturing, shipping, and distributing cell-based therapies present technical challenges and regulatory questions, which many research institutions are not equipped to address. Overall, workshop subjects identified key areas where NCI support might help the research community in driving forward innovation and clinical utility: 1) provide focused research support on topics such as tumor target selection, immune cell fitness and persistence, cell trafficking, and the immunosuppressive tumor microenvironment; 2) support the rapid translation of preclinical findings into proof of concept clinical testing, harmonize clinical trial regimens, and facilitate early trial data sharing (including negative results); 3) expand manufacturing support for cell therapies, including vectors and reagents, and provide training programs for technical staff; and 4) develop and share standard operating procedures for cell handling and analytical assays, and work with the Food and Drug Administration to harmonize product characterization specifications.
Electric stimulation combination with hyperthermia ameliorates pain through inhibition of NLRP3 inflammasome in chronic prostatitis/chronic pelvic pain syndrome
Authors: D. Shin, H.J. Kwon, K.J. Hur, H.W. Moon, Y.H. Park, H.J. Cho, U.S. Ha, S.H. Hong, J.Y. Lee, S.W. Kim, W.J. Bae
Journal: European Urology (2021)