tbuckley/cabot-search huggingface dataset:
Abstract 2977: Organoid-T-cell co-cultures for preclinical testing of adoptive cell and cancer immunotherapy
Authors: Pleun Hombrink, Soura Mardpour, Ewout Spaan, Jarmil Hanrath, Farzin Pourfarzad, Jasper Mullenders, Rene Overmeer, G.J Robert, None Vries, F Sylvia, None Boj
Journal: Cancer Research (2021)

Abstract Recent advances in cancer immunotherapy had a positive impact on the life expectancy of patients with a large range of clinical indications. With new treatment strategies and druggable targets being identified at an increasing pace, the number of patients eligible for cancer immunotherapy is expected to expand steadily. However, promising therapeutic developments face hurdles in translating preclinical findings into therapy. Challenges range from lack of confidence in animal cancer models, inter-tumor heterogeneity and the absence of cellular microenvironment. Hubrecht Organoid Technology (HUB) offers an innovative alternative, build on the discovery that adult stem cells proliferate and organize into three-dimensional organotypic structures when they are embedded into Matrigel. HUBOrganoids™ are generated from healthy and disease tissues and stored as “living” biobanks with high quality and reproducibility. HUB Organoids recapitulate complex characteristics of the original parental tissue, including molecular heterogeneity, and morphological and functional traits. HUB has developed organoid-T-cell co-culture systems that allow a physiologic representation of the complexity of interactions in the tumor microenvironment, which is important for evaluating the effects of novel therapies. HUB offers an innovative platform combining image-based analysis with flow cytometry to visualize and quantify T-cell-tumor interactions as well as measurements of T-cell cytotoxicity against tumor (and normal-matched) organoids for colorectal and several other cancers. Our platform offers a powerful strategy for the development and validation of cancer immunotherapy and may help to screen the efficacy of immune checkpoint blockade or bispecific antibodies. In addition, cancer organoid-T-cell co-culture may also predict the functionality of tumor-infiltrating lymphocytes (TIL) and chimeric antigen receptor (CAR)-engineered T cells. As such, our platform offers opportunities in preclinical development and could become a diagnostic tool to predict individual patient response to immunotherapy. Citation Format: Pleun Hombrink, Soura Mardpour, Ewout Spaan, Jarmil Hanrath, Farzin Pourfarzad, Jasper Mullenders, Rene Overmeer, G.J Robert, Vries, F Sylvia, Boj. Organoid-T-cell co-cultures for preclinical testing of adoptive cell and cancer immunotherapy [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 2977.
Abstract 2447: TLR4 expression as a determinant of EMT and stress response gene expression in UV exposed human keratinocytes
Authors: Viktoria Kirschnerova, Prajakta Vaishampayan, Maria Khawam, Clara Curiel-Lewandrowski, Georg T. Wondrak, Sally E. Dickinson
Journal: Cancer Research (2021)

Abstract Toll-like receptor 4 (TLR4) is gaining attention for its role in several cancer-associated signaling pathways, including the regulation of inflammation, DNA repair and epithelial-mesenchymal transition (EMT). There is evidence that TLR4 contributes to ultraviolet (UV) radiation-induced stress signaling in skin cells, including keratinocytes. Blockade of TLR4 activity using the pharmacological antagonist resatorvid (TAK-242) inhibits not only acute UV-induced signaling in vitro and in vivo, but blocks UV-induced skin carcinogenesis in mouse models. In order to genetically explore the role of TLR4 in keratinocyte responses to UV-induced stress, we recently utilized CRISPR/Cas9 techniques to delete TLR4 from the genome of human HaCaT keratinocyte cells in culture. First, using differential gene expression analysis (employing the EMTRT2 Profiler PCR array technology) it was observed that TLR4 KO status is associated with pronounced downregulation of EMT-related gene expression (MMP9, VIM, FN1, SNAI1, TWIST1) confirmed by independent RT-qPCR analysis. TLR4 was also a determinant of UV-induced inflammatory enzyme expression including PTGS2. Phenotypically, TLR4 KO cells displayed an attenuation of Matrigel transwell migration. TLR4 KO cells demonstrated increased sensitivity to UV-induced apoptosis as detected by flow cytometry of annexin V/propidium iodide stained cells, and by immunodetection of increased PARP cleavage. Moreover, NanoString nCounter expression analysis of murine skin chronically exposed to tumorigenic UV indicated that topical resatorvid treatment was associated with MMP9 downregulation. Future studies will employ this novel TLR4 KO keratinocyte cell line as a mechanistic tool to dissect the role of TLR4 in inflammatory signaling and EMT response in the context of skin photodamage and carcinogenesis. Supported by NIH grants ES029579, R03CA230830, P01CA229112. Citation Format: Viktoria Kirschnerova, Prajakta Vaishampayan, Maria Khawam, Clara Curiel-Lewandrowski, Georg T. Wondrak, Sally E. Dickinson. TLR4 expression as a determinant of EMT and stress response gene expression in UV exposed human keratinocytes [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 2447.
Nitric oxide releasing nanofibrous Fmoc-dipeptide hydrogels for amelioration of renal ischemia/reperfusion injury
Authors: Haniyeh Najafi, Samira Sadat Abolmaali, Reza Heidari, Hadi Valizadeh, Mahboobeh Jafari, Ali Mohammad Tamaddon, Negar Azarpira
Journal: Journal of Controlled Release (2021)
Abstract 90: Fatty acid synthesis is required for breast cancer brain metastasis
Authors: Gino B. Ferraro, Ahmed Ali, Alba Luengo, David P. Kodack, Amy Deik, Keene L. Abbott, Divya Bezwada, Landry Blanc, Brendan Prideaux, Xin Jin, Jessica M. Possada, Jiang Chen, Christopher R. Chin, Zohreh Amoozgar, Raphael Ferreira, Ivy Chen, Kamila Naxerova, Christopher Ng, Anna M. Westermark, Mark Duquette, Sylvie Roberge, Costas A. Lyssiotis, Dan G. Duda, Todd R. Golub, Shawn M. Davidson, Dai Fukumura, Véronique A. Dartois, Clary B. Clish, Matthew G. Vander Heiden, Rakesh K. Jain
Journal: Cancer Research (2021)

Abstract Brain metastases are refractory to therapies that otherwise control systemic disease in patients with human epidermal growth factor receptor 2 (HER2+) breast cancer, and the unique brain microenvironment contributes to this therapy resistance. Nutrient availability can vary across tissues, therefore metabolic adaptations required for breast cancer growth in the brain microenvironment may also introduce liabilities that can be exploited for therapy. Here, we assessed how metabolism differs between breast tumors growing in the brain versus extracranial sites and found that fatty acid synthesis is elevated in breast tumors growing in the brain. We determine that this phenotype is an adaptation to decreased lipid availability in the brain relative to other tissues, which results in a site-specific dependency on fatty acid synthesis for breast tumors growing at this site. Genetic or pharmacological inhibition of fatty acid synthase (FASN) reduces HER2+ breast tumor growth in the brain, demonstrating that differences in nutrient availability across metastatic sites can result in targetable metabolic dependencies. Citation Format: Gino B. Ferraro, Ahmed Ali, Alba Luengo, David P. Kodack, Amy Deik, Keene L. Abbott, Divya Bezwada, Landry Blanc, Brendan Prideaux, Xin Jin, Jessica M. Possada, Jiang Chen, Christopher R. Chin, Zohreh Amoozgar, Raphael Ferreira, Ivy Chen, Kamila Naxerova, Christopher Ng, Anna M. Westermark, Mark Duquette, Sylvie Roberge, Costas A. Lyssiotis, Dan G. Duda, Todd R. Golub, Shawn M. Davidson, Dai Fukumura, Véronique A. Dartois, Clary B. Clish, Matthew G. Vander Heiden, Rakesh K. Jain. Fatty acid synthesis is required for breast cancer brain metastasis [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 90.
Abstract 360: The dilemma of the current diagnostic tests for MSI in prostate cancer
Authors: Esra Dikoglu, Xu Naizhen, Luke P. O'Connor, Peter Pinto, Maria J. Merino
Journal: Cancer Research (2021)

Abstract Background: Understanding the relationship between tumor genomics and the immune response in cancer has gotten more attention with the advance of immunotherapy. Microsatellite instability (MSI) is a molecular marker that provides prognostic and predictive information in many types of tumors including prostate cancer (PC). In PC, MSI-H and dMMR have been reported anywhere from 1% in primary tumors to up to 12% in metastasis. Reliable testing strategies for MSI/MMR status are critical for clinical management of patients with PC. MSI detection methods include PCR based molecular tests, NGS-based MSI detection or immunohistochemical staining (IHC). We observe technical difficulties in our daily practice with current molecular diagnostic tests. Design: We examined MMR protein expression (MSH2, MSH6, MLH1, PMS2) and PD-L1 by IHC in 30 PC. Results: Among 30 PC tested, 1 tumor (3%) was completely negative for MLH1 and PMS2 and 1 tumor (3%) revealed loss of PMS2 by IHC even though gene panel did not reveal any mutation in PMS2. The PD-L1 IHC was 44% positive, but the single MMR negative biopsy was PD-L1 negative. PD-L1 expression in PC samples did not show correlation with defective MMR expression. Conclusion: In our study, controversial results were obtained. Based on our experience; even though many exons of MMR genes are covered with these panels, there are some exons do not get enough coverage to be analyzed. This low coverage problem creates false negative results. There are also pseudogene pairs of these genes, especially PMS2. For some specific regions, even though there is enough coverage it is impossible to know if the pathogenic variant is on the PMS2 or the pseudogene without additional test. This result suffers from false positive results without a confirmatory test. It is also known that 5% to 11% of MSI-H cases demonstrate intact MMR staining and localization (proficient MMR, pMMR) due to retained antigenicity and nonfunctional protein. So far, in regular practice we use MMR analyzing strategies which set up for colon cancer where the tumor is uniform. PC is more complex; most of the time more than one clone is involving.We believe MSI detection for PC requires improvement the technics of detection, robust set up of testing strategy with high sensitivity and specificity, analyzing strategy and training of pathologists. Due to technical difficulties of the detection, we believe that the prevalence of MSI-high/dMMR PC might be higher than reported in the literature so far. Citation Format: Esra Dikoglu, Xu Naizhen, Luke P. O'Connor, Peter Pinto, Maria J. Merino. The dilemma of the current diagnostic tests for MSI in prostate cancer [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 360.
Retzius-sparing robot-assisted radical prostatectomy in high-risk prostate cancer patients: Results from a large single institution series
Authors: P. Dell’Oglio, S. Tappero, M. Longoni, C. Buratto, P. Scilipoti, S. Secco, A. Olivero, M. Barbieri, G. Napoli, D. Di Trapani, A.M. Bocciardi, A. Galfano
Journal: European Urology (2021)
Sources of Individual Differences in Pain
Authors: Jeffrey S. Mogil
Journal: Annual Review of Neuroscience (2021)

Pain is an immense clinical and societal challenge, and the key to understanding and treating it is variability. Robust interindividual differences are consistently observed in pain sensitivity, susceptibility to developing painful disorders, and response to analgesic manipulations. This review examines the causes of this variability, including both organismic and environmental sources. Chronic pain development is a textbook example of a gene-environment interaction, requiring both chance initiating events (e.g., trauma, infection) and more immutable risk factors. The focus is on genetic factors, since twin studies have determined that a plurality of the variance likely derives from inherited genetic variants, but sex, age, ethnicity, personality variables, and environmental factors are also considered.
Properties of the EQ-5D-5L when prospective longitudinal data from 28,902 total hip arthroplasty procedures are applied to different European EQ-5D-5L value sets
Authors: Anders Joelson, Peter Wildeman, Freyr Gauti Sigmundsson, Ola Rolfson, Jan Karlsson
Journal: The Lancet Regional Health - Europe (2021)

The purpose of this study was to evaluate the impact of using different country-specific value sets in EQ-5D-5L based outcome analyses.We obtained data on patients surgically treated with total hip arthroplasty (THA) between 2017 and 2019 from the national Swedish Hip Arthroplasty Register. Preoperative and one-year postoperative data on a total of 28,902 procedures were available for analysis. The EQ-5D-5L health states were coded to the EQ-5D-5L preference indices using 13 European value sets. The EQ-5D-5L index distributions were then estimated with kernel density estimation. The change in EQ-5D-5L index before and one year after treatment was evaluated with the standardized response mean (SRM). The lifetime gain in quality-adjusted life years (QALYs) was estimated with a 3.5% annual QALY discount rate.There was a marked variability in means and shapes of the resulting EQ-5D-5L index distributions. There were also considerable differences in the EQ-5D-5L index distribution shape before and after the treatment using the same value set. The effect sizes of one-year change (SRM) were similar for all value sets. However, the differences in estimated QALY gains were substantial.The EQ-5D-5L index distributions varied considerably when a single large data set was applied to different European EQ-5D-5L value sets. The most pronounced differences were between the value sets based on experience-based valuation and the value sets based on hypothetical valuation. This illustrates that experience-based and hypothetical value sets are inherently different and also that QALY gains derived with different value sets are not comparable. Our findings are of importance in study planning since the results and conclusions of a study depend on the choice of value set.None.
炭水化物摂取を抑制する腹内側視床下部におけるグルタミン酸作動性ニューロンへのFGF21シグナル【JST・京大機械翻訳】
Authors: O Jensen-Cody Sharon, H Flippo Kyle, E Claflin Kristin, Yavuz Yavuz, A Sapouckey Sarah, C Walters Grant, M Usachev Yuriy, Atasoy Deniz, P Gillum Matthew, J Potthoff Matthew
Journal: Cell Metabolism (2020)
Cost analysis and perioperative outcomes between mini-percutaneous nephrolithotomy with vacuum cleaner effect or with a vacuum-assisted access sheath
Authors: L. Boeri, I. Fulgheri, E. Lievore, M. Turetti, C. Bebi, F. Ripa, L. Rocchini, E. De Lorenzis, G. Albo, F. Longo, E. Montanari
Journal: European Urology (2021)
Abstract 2168: Multi-regional RNA-Seq reveals pattern of RNA-editing in brain tumor
Authors: Cheng Yan, Jun Wu, Dan Wang, Lan Su, Yufei Yang
Journal: Cancer Research (2021)

Abstract Introduction: RNA-editing is widespread across human genome. Previous studies have observed that RNA editing level differs significantly across multiple cancer types and may influence cancer development. Increased level of RNA editing has been found to correlate with enhanced tumorigenesis in some cancers but reduced tumorigenesis in others. In brain tumor, the RNA editing landscape has not been well characterized partially due to the difficulty of sample accessibility. We performed multi-regional RNA-Seq on cancerous, peritumoral and distant tissue collected from 40 brain cancer patients. Our aim is to depict the landscape of RNA editing and to comprehend the relevance of RNA editing with other molecular characteristics of brain cancer. Methods: We collected 40 cancerous brain tissue sample (30 LGG and 10 GBM), each coupled with a peritumoral tissue and a distant tissue. These 120 samples were subjected to RNA-Seq sequencing. RNACocktail was applied for identification of RNA editing events. RADAR and ANNOVAR were used for identification and annotation of A-to-I editing sites. RNAEditingIndexer was used to estimate sample-wise editing level denoted as AEI. Pathway enrichment analysis was performed using GSEA. Statistical difference of molecular characteristics between sample groups was calculated using either Wilcoxon signed rank test or Kruskal-Wallis test. Results: A total number of 21,105 and 5,634 informative editing events were identified in LGG and GBM respectively. As expected, most editing events were located within Alu element of intronic and 3'UTR region. In both LGG and GBM, RNA editing level showed decreasing trend from distant to peritumoral to cancerous samples. Compared with normal tissue, we found 5.12‰ up-regulated events and 16.92‰ down-regulated events in LGG samples. Similar pattern was found in GBM as well. We found two editing sites with significant editing differences (adjust p-value &amp;lt; 0.05) within coding region of GRIK2 and NEIL1 gene. In addition, numerous editing sites showed statistical correlation other molecular/pathological characteristics such as IDH1 mutation, existence of seizure, MGMT methylation and pathological classification. At sample level, the same decreasing trend of RNA editing level was consistently observed from distant to cancerous tissue. Enrichment analysis showed that editing level was positively correlated with neural transmission and oncogenic related pathways. In addition, sample level editing was significant different between WHO as well as pathological classification. Citation Format: Cheng Yan, Jun Wu, Dan Wang, Lan Su, Yufei Yang. Multi-regional RNA-Seq reveals pattern of RNA-editing in brain tumor [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 2168.
Infection and Vaccine-Induced Neutralizing-Antibody Responses to the SARS-CoV-2 B.1.617 Variants
Authors: Venkata-Viswanadh Edara, Benjamin A. Pinsky, Mehul S. Suthar, Lilin Lai, Meredith E. Davis-Gardner, Katharine Floyd, Maria W. Flowers, Jens Wrammert, Laila Hussaini, Caroline Rose Ciric, Sarah Bechnak, Kathy Stephens, Barney S. Graham, Elham Bayat Mokhtari, Prakriti Mudvari, Eli Boritz, Adrian Creanga, Amarendra Pegu, Alexandrine Derrien-Colemyn, Amy R. Henry, Matthew Gagne, Daniel C. Douek, Malaya K. Sahoo, Mamdouh Sibai, Daniel Solis, Richard J. Webby, Trushar Jeevan, Thomas P. Fabrizio
Journal: New England Journal of Medicine (2021)

actions were reported in patients who were Asian (27 [5%]); of mixed race, which included American Indian-Alaska Native and Native ) ; and Black (6 [1%]).Six of these patients (11%) were Hispanic.A majority of these delayed large local reactions occurred after the receipt of the first vaccine dose (in 53 patients [96%]) and after the receipt of the mRNA-1273 vaccine (in 47 [85%]).The mean time from vaccination until the onset of the reaction was 8±2 days (range, 4 to 14).Eleven patients (20%) had cutaneous reactions other than at the injection site, such as diffuse itching, hives or other rash, or angioedema.Delayed large local reactions may be less commonly recognized or reported in BIPOC vaccine recipients than in White recipients.Such reactions may result in vaccine hesitancy or incomplete vaccination; as such, proactive outreach is needed to increase education regarding these reactions across diverse communities.We hope that this letter encourages additional research and communication regarding cutaneous vaccine reactions, including delayed large local reactions, in BIPOC recipients.
Abstract 3106: Roles of extracellular ATP in inducing cancer stem cell (CSC)-like changes in non-small lung cancer cell line
Authors: Jingwen Song, Xiaozhuo Chen
Journal: Cancer Research (2021)

Abstract Cancer is a major death-causing disease worldwide, and metastasis, a hallmark of cancer, is associated with up to 90% of all cancer-related deaths. Metastasis requires ATP, and the tumor microenvironment (TME) has much higher concentrations of intratumoral and extracellular ATP (eATP) than healthy tissue, implying that eATP may have potential roles in tumor development and progression. Our previous ATP studies, cited by a Nature Review Cancer paper in 20181 showed that eATP is internalized by cancer cell through macropinocytosis, and it promotes cancer cell growth, survival, and drug resistance. However, how intratumoral eATP plays roles in metastasis remains largely unclear. Our 2019 published results show that eATP promotes cancer migration and invasion, initiates epithelial to mesenchymal transition (EMT), alters expression level of EMT related protein markers such as ZEB1, SNAIL, SLUG in human non-small lung cancer cell (NSCLC) lines2. It has been reported that the EMT and cancer stem cells (CSCs) share some molecular links, but the detailed mechanisms involved are still unknown. Recently, we have found the eATP significantly induces the protein expression level of CSC related makers in A549 cells. We have also found that, after A549 cells were treated with 0.5mM and 0.75mM ATP for 6 and 24 hours, the ATP treated A549 cells were able to show significantly increased colony numbers by soft agar colony formation assay. Based on all these results, we hypothesize that extracellular ATP functions as a messenger, a signal facilitator, an energy molecule, and a transcription cofactor to induce CSC-like features to promote metastasis in NSCLC. RNAseq and metabolomics studies are being used to determine the transcriptional and metabolic changes associated with the ATP induced CSC process in NSCLC. The completion of the study will not only unravel eATP's roles in CSC induction and early steps of tumor metastasis, but also potentially provide novel promising therapeutic targets for inhibiting tumor metastasis.(1) Di Virgilio, F., Sarti, A. C., Falzoni, S., De Marchi, E., &amp; Adinolfi, E. (2018). Extracellular ATP and P2 purinergic signaling in the tumor microenvironment. Nature Reviews Cancer, 18(10), 601-618. (2) Cao, Y., Wang, X., Li, Y., Evers, M., Zhang, H., &amp; Chen, X. (2019). Extracellular and macropinocytosis internalized ATP work together to induce epithelial-mesenchymal transition and other early metastatic activities in lung cancer. Cancer Cell International, 19(1). Citation Format: Jingwen Song, Xiaozhuo Chen. Roles of extracellular ATP in inducing cancer stem cell (CSC)-like changes in non-small lung cancer cell line [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 3106.
Combined anti-hepatocellular carcinoma therapy inhibit drug-resistance and metastasis via targeting “substance P-hepatic stellate cells-hepatocellular carcinoma” axis
Authors: Zhipeng Li, Fangqing Wang, Yanying Li, Xiaoxue Wang, Qiao Lu, Di Wang, Cuiping Qi, Chenglei Li, Zhaohuan Li, Bo Lian, Guixiang Tian, Zhiqin Gao, Bo Zhang, Jingliang Wu
Journal: Biomaterials (2021)