tbuckley/cabot-search huggingface dataset:
Abstract 331: Characterization of neoepitope (neoE)-specific T cells from peripheral blood for adoptive neoTCR-T cell therapy for patients with breast cancer (bc) or ovarian cancer (oc)
Authors: Mihaela Cristea, Bartosz Chmielowski, David Y. Oh, Roel P. Funke, Daniela A. Bota, Mehrdad Abedi
Journal: Cancer Research (2021)

Abstract Introduction: Broad application of neoTCR-T cell therapy involves isolation of mutation-targeted CD8 T cells from the blood of patients with different tumor types. An ultra-sensitive process streamlined for high-throughput capture of neoE-specific T cells from blood is leveraged for producing a fully personalized adoptive T cell therapy for trial participants with BC or OC (NCT03970382). Methods: Expressed mutations were identified by comparative sequencing of blood cells and tumor tissue. HLA typing was performed with OpiType. Proprietary algorithms were used to predict and prioritize tumor-exclusive neoE-HLA candidates. A library of barcoded HLA-mutational neoantigen complexes was used to interrogate PBMCs from each patient using imPACT Isolation Technology® (Dalmas et al., 2020). NeoTCRs cloned from captured antigen-experienced CD8 T cells were precision genome engineered into healthy donor T cells for functional characterization, including secretion of cytokines and effector molecules (Jacoby et al., 2019; Sennino et al., 2019). Based on pre-specified prioritization criteria, up to 3 actionable neoTCRs were selected for manufacturing the products for each individual. Results: Six patients (2 BC/4 OC) successfully underwent neoTCR product selection. The median age was 59.5 years (range 38-69). Patients received a median of 5.5 prior regimens for metastatic disease (range 4-9). Median tumor mutational burden (TMB) was 2.7 (range 0.9-13.4). HLA-neoantigen libraries contained a median of 91 snares (range 29-262) and represented 6/6 HLA alleles in 4 patients and 5/6 in the remaining 2. A median of 8.5 distinct neoE-specific T cells (range 5-15) were isolated per patient. Following functional characterization 13 neoTCRs met selection criteria: three patients with 3 TCRs, one with 2 TCRs, and two had a single TCR. The median predicted neoE:HLA affinity of the selected TCRs was 77 nM (range 6.3 - 5866) and the median IFN-g EC50 was 4 ng/mL (range 1-431). Conclusion: Relevant antigen-experienced, tumor mutation-targeted CD8 T cells were isolated from the blood of heavily pre-treated BC and OC patients with low TMB (&amp;lt;10 mutations/Mb). Correlations between TCR characteristics and clinical and biomarker data are planned. This approach holds potential for broad use in women with BC or OC. Citation Format: Mihaela Cristea, Bartosz Chmielowski, David Y. Oh, Roel P. Funke, Daniela A. Bota, Mehrdad Abedi. Characterization of neoepitope (neoE)-specific T cells from peripheral blood for adoptive neoTCR-T cell therapy for patients with breast cancer (bc) or ovarian cancer (oc) [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 331.
ThuLEP vs. open simple prostatectomy for the treatment of prostates larger than 150 cc
Authors: L. Berti, M. Maltagliati, C. Buizza, U. Besana, A. Calori, D. Antonelli, M. Justich, P. Marcangeli, S. Micali, M.C. Sighinolfi, B. Rocco, G. Bozzini
Journal: European Urology (2021)
Efficacy of dapagliflozin in heart failure with reduced ejection fraction according to body mass index
Authors: Carly Adamson, Pardeep S. Jhund, Kieran F. Docherty, Jan Bělohlávek, Chern‐En Chiang, Mirta Diez, Jarosław Drożdż, Andrej Dukát, Jonathan Howlett, Charlotta E.A. Ljungman, Mark C. Petrie, Morten Schou, Silvio E. Inzucchi, Lars Køber, Mikhail N. Kosiborod, Felipe A. Martinez, Piotr Ponikowski, Marc S. Sabatine, Scott D. Solomon, Olof Bengtsson, Anna Maria Langkilde, Daniel Lindholm, Mikaela Sjöstrand, John J.V. McMurray
Journal: European Journal of Heart Failure (2021)
Abstract 739: Preclinical and clinical activity of SAR439859, Amcenestrant, a next generation SERD
Authors: Maysoun Shomali, Fangxian Sun, Laurent Besret, Anne Caron, Joon Sang Lee, Youssef El-Ahmed, Laurent Schio, Jack Pollard, Vasiliki Pelekanou, Patrick Cohen, Marina Celanovic, Christina Herold, Chris Soria, Laurent Debussche, Monsif Bouaboula
Journal: Cancer Research (2021)

Abstract Primary treatment for estrogen receptor-positive (ER+) breast cancer is endocrine therapy. Selective estrogen receptor degraders (SERDs), such as fulvestrant, induce effective ER signaling inhibition, although clinical studies with fulvestrant report insufficient blockade of ER signaling, possibly due to suboptimal pharmaceutical properties. Here we describe the discovery of SAR439859 (Amcenestrant), a novel, orally bioavailable SERD with potent antagonist and degradation activities against both wild-type and mutant Y537S ER. Driven by its fluoropropyl pyrrolidinyl side chain, SAR439859 has demonstrated broader and superior ER antagonist and degrader activities across a large panel of ER+ cells, compared with other SERDs including improved inhibition of ER signaling and tumor cell growth. Similarly, in vivo treatment with SAR439859 demonstrated significant tumor regression in ER+ breast cancer models including MCF7-ESR1 mutant-Y537S mouse tumors and HCI013, a patient-derived tamoxifen-resistant xenograft tumor. Importantly, in these mutant ESR1 models, we demonstrate that the efficacy of SAR439859 was increased when coadministered with palbociclib, an inhibitor of cyclin-dependent kinase 4 and 6. In the clinical setting, SAR439859 also demonstrated a high level of target engagement, ER degradation and inhibition of ER signaling as well as encouraging anti-tumor activity in heavily pretreated patients with advanced or metastatic ER-positive breast cancer. These findings indicate that SAR439859 would provide therapeutic benefit to patients with ER+ breast cancer, including those who are resistant to endocrine therapy with both wild-type and mutant ER. Citation Format: Maysoun Shomali, Fangxian Sun, Laurent Besret, Anne Caron, Joon Sang Lee, Youssef El-Ahmed, Laurent Schio, Jack Pollard, Vasiliki Pelekanou, Patrick Cohen, Marina Celanovic, Christina Herold, Chris Soria, Laurent Debussche, Monsif Bouaboula. Preclinical and clinical activity of SAR439859, Amcenestrant, a next generation SERD [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 739.
Black and Latinx Community Perspectives on COVID-19 Mitigation Behaviors, Testing, and Vaccines
Authors: Manuel E. Jimenez, Zorimar Rivera-Núñez, Benjamin F. Crabtree, Diane Hill, Maria B. Pellerano, Donita Devance, Myneka Macenat, Daniel Lima, Emmanuel Martinez Alcaraz, Jeanne M. Ferrante, Emily S. Barrett, Martin J. Blaser, Reynold A. Panettieri, Shawna V. Hudson
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Black and Latinx communities have been disproportionately affected by the COVID-19 pandemic, yet little work has sought to understand their perspectives. <h3>Objective</h3> To explore the experiences of Black and Latinx communities during the pandemic to better understand their perspectives on COVID-19 mitigation behaviors (eg, mask wearing), testing, and vaccines. <h3>Design, Setting, and Participants</h3> In this community-engaged qualitative study conducted with 18 community-based organizations and 4 health care organizations between November 19, 2020, and February 5, 2021, in New Jersey counties severely affected by the pandemic, group and individual interviews were used to purposively sample 111 Black and Latinx individuals. A total of 13 group interviews were organized by race/ethnicity and language: 4 English-speaking groups with Black participants (n = 34), 3 Spanish-speaking groups with Latinx participants (n = 24), and 4 English-speaking groups with Black and Latinx participants (n = 36). To understand the views of health care workers from these communities, 2 additional groups (n = 9) were convened and supplemented with individual interviews. <h3>Main Outcomes and Measures</h3> Description of Black and Latinx participants' experiences during the COVID-19 pandemic and their perspectives on mitigation behaviors, testing, and vaccines. <h3>Results</h3> The study included 111 participants (87 women [78.4%]; median age, 43 years [range, 18-93 years]). Participants described the devastating effects of the pandemic on themselves, loved ones, and their community. Their experiences were marked by fear, illness, loss, and separation. These experiences motivated intense information seeking, mitigation behaviors, and testing. Nevertheless, vaccine skepticism was high across all groups. Participants did not trust the vaccine development process and wanted clearer information. Black participants expressed that they did not want to be subjects of experiments. <h3>Conclusions and Relevance</h3> The remaining unknowns about new vaccines need to be acknowledged and described for Black and Latinx communities to make informed decisions. Ultimately, scientists and public officials need to work transparently to address unanswered questions and work collaboratively with trusted community leaders and health professionals to foster partnered approaches, rather than focusing on marketing campaigns, to eliminate vaccine skepticism.
誘導治療での高投与量シタラビンは46歳より若い急性骨髄性白血病成人患者の転帰を改善する: EORTC-GIMEMA AML-12試験
Authors: Willemze Roelof, Suciu Stefan, Meloni Giovanna, Labar Boris, Marie Jean-Pierre, J M Halkes Constantijn, Muus Petra, Mistrik Martin, Amadori Sergio, Specchia Giorgina, Fabbiano Francesco, Nobile Francesco, Sborgia Marco, Camera Andrea, L D Selleslag Dominik, Lefrere Francois, Magro Domenico, Sica Simona, Cantore Nicola, Beksac Meral, Berneman Zwi, Thomas Xavier, Melillo Lorella, E Guimaraes Jose, Leoni Pietro, Luppi Mario, E Mitra Maria, Bron Dominique, Fillet Georges, W A Marijt Erik, Venditti Adriano, Hagemeijer Anne, Mancini Marco, Jansen Joop, Cilloni Daniela, Meert Liv, Fazi Paola, Vignetti Marco, M Trisolini Silvia
Journal: Journal of Clinical Oncology (2014)
Upper gastrointestinal bleeding due to mixed adenoneuroendocrine carcinoma and radiation esophagitis treated with cap-mucosectomy combined with radiofrequency ablation
Authors: Laurent Monino, Rodrigo Garces-Duran, Pierre H. Deprez, Tom G. Moreels
Journal: Endoscopy (2021)

The management of upper gastrointestinal bleeding is standardized according to European Society of Gastrointestinal Endoscopy guidelines [1]. Telangiectasias due to radiation esophagitis are classically managed with argon plasma coagulation (APC) [2] [3]. Radiological or surgical management is proposed when APC treatment fails with ongoing bleeding due to radiation esophagitis. Mixed adenoneuroendocrine carcinoma (MANEC) is a rare complication of Barrett’s esophagus [4]. Endoscopic resection of localized MANEC can be performed, whereas in cases of extensive MANEC, chemotherapy and radiotherapy are indicated. Recently, radiofrequency ablation (RFA) has been used to treat Barrett’s esophagus with low or high grade dysplasia without visible lesions [5]. RFA allows cicatrization scarification of esophageal mucosa without recurrence of Barrett. We report a case of chronic esophageal bleeding due to recurrent MANEC combined with radiation-induced telangiectasias, treated successfully with the combination of cap-mucosectomy and RFA.
The role of a digital psychological support for prostate cancer patients managed by a multidisciplinary disease unit: Initial experience from a referral center
Authors: M. Sironi, R. Leni, G. Gandaglia, N. Fossati, S. Foti, A. Fodor, C.L. De Antoni, S. Clerici, F. Montorsi, A. Briganti
Journal: European Urology (2021)
Abstract 2857: Asparagine synthetase regulate β-catenin dependent lung cancer metastasis
Authors: Dong-Jing Cai, Cheng-Ping Hu, Li li, Zi-Yu Zhang, Yuan-Mao Li, Min Li
Journal: Cancer Research (2021)

Abstract Objective: Lung cancer was a malignant tumor with high morbidity and mortality. The lead cause of lung cancer-related death was metastasis. Asparagine synthetase (ASNS) that was a key enzyme to convert glutamine to asparagine played important role in cell metabolism. Based on previous metabolomics data, the high level of asparagine synthase was significantly correlated with tumor metastasis. The purpose of this study was to investigate the role of asparagine synthase in lung cancer metastasis, furthermore for anti-cancer target therapy. Method: For pursuing high ASNS correlated to metastasis, a cohort were collected from Xiangya hospital. And selected paired lung cancer cell lines were used for discovering potential molecular interactions. Importantly, some key molecules or pathways were found by cell biology study and bioinformatics analysis. In the part of cellular and molecule study, Transwell, scratch test, Western blot, immunofluorescence, immunohistochemistry and co-immunoprecipitation experiments were used. The results of the inquiry were validated by using a mouse metastasis model. Results: With provided from Xiangya hospital and TCGA cohort, we could validate high ASNS had relations to patient's metastasis and survival. In part of cell biology study, high wild-type ASNS could promote lung cancer cell metastasis and proliferation in vivo and vitro. Overexpression of amidotransferase-dysfunction ASNS had partially potential to drive metastasis but have nothing to increase cell proliferation. Furthermore, Wnt/β-catenin cascades were responsible for tumor mestasis among wild-type and amidotransferase-mutated type groups. The accumulation and nuclear location of β-catenin definitely depend on high ASNS expression even with amidotransferase mutation. With processing, ASNS possible interacted with key proteins located in Wnt/β-catenin signaling pathway to mediate signal conduction. But the activation of ASNS amidotransferase was necessary to promoted tumor proliferation. Conclusion: ASNS promoted metastasis by mediating Wnt/β-catenin signaling conduction even without ASNS amidotransferase activity, while cell proliferation was required for amidotransferase function. Maybe dual inhibition of ASNS and Wnt/β-catenin would be an effective target for anti-tumor metastasis and proliferation. Key Words: ASNS, metastasis, lung cancer, β-catenin Citation Format: Dong-Jing Cai, Cheng-Ping Hu, Li li, Zi-Yu Zhang, Yuan-Mao Li, Min Li. Asparagine synthetase regulate β-catenin dependent lung cancer 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 2857.
Association of Coding Variants in Hydroxysteroid 17-beta Dehydrogenase 14 (HSD17B14) with Reduced Progression to End Stage Kidney Disease in Type 1 Diabetes
Authors: Josyf C. Mychaleckyj, Erkka Valo, Takaharu Ichimura, Tarunveer S. Ahluwalia, Christian Dina, Rachel G. Miller, Ivan G. Shabalin, Beata Gyorgy, JingJing Cao, Suna Onengut-Gumuscu, Eiichiro Satake, Adam M. Smiles, Jani K. Haukka, David-Alexandre Tregouet, Tina Costacou, Kristina O’Neil, Andrew D. Paterson, Carol Forsblom, Hillary A. Keenan, Marcus G. Pezzolesi, Marlon Pragnell, Andrzej Galecki, Stephen S. Rich, Niina Sandholm, Ronald Klein, Barbara E. Klein, Katalin Susztak, Trevor J. Orchard, Ron Korstanje, George L. King, Samy Hadjadj, Peter Rossing, Joseph V. Bonventre, Per-Henrik Groop, James H. Warram, Andrzej S. Krolewski
Journal: Journal of the American Society of Nephrology (2021)

Rare variants in gene coding regions likely have a greater impact on disease-related phenotypes than common variants through disruption of their encoded protein. We searched for rare variants associated with onset of ESKD in individuals with type 1 diabetes at advanced kidney disease stage.
Abstract CT232: A phase II study of toripalimab plus anlotinib as maintenance therapy in extensive-stage small cell lung cancer
Authors: Dongqing Lv, Guixian Wu, Xiaomai Lin, Ling Lin, Weijia Pan
Journal: Cancer Research (2021)

Abstract A phase II study of toripalimab plus anlotinib as maintenance therapy in extensive-stage small cell lung cancer Background: Maintenance therapy is a promising therapeutic approach for extensive-stage small cell lung cancer (ES-SCLC), especially in light of the IMpower 133 trial (Horn NEJM 2018). The results of the E3501, SALUTE, and CALGB 30306 trials showed that in first-line treatment of ES-SCLC, bevacizumab combined with chemotherapy improved only progression-free survival (PFS) but not overall survival (OS). However, in the ALTER 1202 study, anlotinib used as a third- or further-line treatment in patients with ES-SCLC improved PFS and OS (Cheng WCLC 2018). Toripalimab is a novel PD-1 inhibitor that, when combined with anlotinib as maintenance therapy for ES-SCLC, may improve disease control.Methods: This is a phase 2, single-arm study of toripalimab plus anlotinib, a vascular endothelial growth factor receptor inhibitor, as maintenance therapy in adult patients with ES-SCLC following their completion of platinum-based first-line chemotherapy. Eligible patients must have measurable (RECIST v1.1) ES-SCLC, an ECOG performance status of 0 or 1, and are required to have shown complete response, partial response, or stable disease as per RECIST 1.1 following 4–6 cycles of platinum-based chemotherapy. Twenty participants will be enrolled to receive toripalimab (240 mg, IV, Q3W) + anlotinib (12 mg, oral, Q3W). Patients will be treated until the disease progresses, unacceptable toxicity occurs, or for up to 2 years. Prophylactic cranial irradiation will be permitted at the investigator's discretion. The primary endpoints are PFS and OS. Secondary endpoints include safety, objective response rate, disease control rate, and time to response. Exploratory endpoints include Tumor Mutational Burden (TMB) and PD-L1 protein expression, immune gene transcript expression (PD-1, PD-L1, CTLA-4, and others) ,and correlation of these endpoints with clinical responses and drug resistance. This study is currently open and accruing patients. Clinical trial information: NCT04363255. Research Sponsor: Shanghai Junshi Biosciences Co. Citation Format: Dongqing Lv, Guixian Wu, Xiaomai Lin, Ling Lin, Weijia Pan. A phase II study of toripalimab plus anlotinib as maintenance therapy in extensive-stage small cell lung 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 CT232.
Splice variant V1 of HYAL4 causes Gemcitabine resistance and predicts Gemcitabine/ Cisplatin failure in metastatic bladder cancer
Authors: M.C. Hupe, M.J.P.. Hennig, S. Lokeshwar, S.L. Hasanali, D.S. Morera, S. Sarcan, M.K. Terris, A.S. Merseburger, V.B. Lokeshwar
Journal: European Urology (2021)
Abstract 1806: Novel preclinical orthotopic and bone metastasis TNBC models for assessment of immunotherapy and chemotherapy responses
Authors: Justyna Zdrojewska, Ivan Gladwyn-Ng, Jenni H. Mäki-Jouppila, Katja M. Fagerlund, Mari I. Suominen, Ross Horn, Jukka Rissanen
Journal: Cancer Research (2021)

Abstract Triple-negative breast cancer (TNBC) is one of the most complicated types of breast cancer to treat. However, clinical trials continue to demonstrate that combining immunotherapy with chemotherapy can improve survival in patients with metastatic TNBC. In preclinical immunotherapy development, one of the challenges and limitations is the lack of representative TNBC models for advanced metastatic disease that could be used to study survival benefit of these compounds. The aim of this study was to develop local and bone metastatic TNBC models where survival could be followed as primary endpoint, and to assess effects of standard-of-care (Nab-paclitaxel, Abraxane) and anti-PD-1 (pembrolizumab, Keytruda). Age-matched immunodeficient female CIEA NOG® mice (NOG) and NOG mice engrafted with human CD34+ hematopoietic stem cells (huNOG) were used in the study. In the orthotopic model, the luciferase labelled human TNBC cells, MDA-MB-231(SA)-luc, were inoculated into mammary fat pad of the mice. In the intratibial model, MDA-MB-231(SA)-luc cells were inoculated into bone marrow cavity of tibia to model the growth of primary and bone metastatic TNBC. The treatment with vehicle or paclitaxel (10 mg/kg) in NOG mice or isotype control or pembrolizumab (5 mg/kg) in huNOG mice was started 3 days after cancer cell inoculation and continued twice a week until termination. The mice were sacrificed individually according to predefined sacrifice criteria or latest at study week 8. Nab-paclitaxel prolonged survival of immunodeficient mice with both primary and metastatic TNBC, but the effect was more profound in the orthotopic model. Pembrolizumab treatment in humanized mice with either tumor site did not result in survival benefit. In an earlier study, we have observed modest tumor growth inhibition with pembrolizumab in the orthotopic model suggesting donor variation effect. The findings are consistent with the clinical studies where pembrolizumab as monotherapy has demonstrated benefit for only some of the TNBC patients. In summary, novel preclinical models mimicking primary and bone metastatic TNBC were established that could be used to study the survival benefit of developing new treatments, including immunotherapies, against local and advanced TNBC. Citation Format: Justyna Zdrojewska, Ivan Gladwyn-Ng, Jenni H. Mäki-Jouppila, Katja M. Fagerlund, Mari I. Suominen, Ross Horn, Jukka Rissanen. Novel preclinical orthotopic and bone metastasis TNBC models for assessment of immunotherapy and chemotherapy responses [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 1806.