tbuckley/cabot-search huggingface dataset:
Abstract 996: Cold atmospheric plasma therapy selectively targets triple negative breast cancer cells
Authors: Peiyu Wang, Renwu Zhou, Rusen Zhou, Jennifer Gunter, Fiona Simpson, Kostya (Ken) Ostrikov, Derek Richard, Xiaofeng Dai, Erik (Rik) Walter Thompson
Journal: Cancer Research (2021)

Abstract Background: Cancer cells notoriously escape radiation therapy, chemotherapy, hormonal therapy, and other anti-cancer therapies. Among various breast cancer subtypes, triple negative breast cancers (TNBCs) are known for their poor clinical outcome and dearth of effective targeted therapies due to the absence of druggable receptors. Cold atmospheric plasma (CAP) holds promise as a cancer-specific treatment agent that selectively kills basal-like/TN breast cancer cells. Method: In this study, we used plasma-activated media (PAM) to capture and store the multi-modal chemical species of CAP, which significantly expands the treatment scope and flexibility of plasma medicine as a clinical therapeutic approach. The PAM was diluted into different doses and cells were treated for 12 or 24 hours. The effects of PAM on cell viability and ROS levels in 9 different cell lines; normal cells (MCF-10A and HEK-293T), luminal breast cancer cell lines (MCF-7, T47D, HCC70), and TNBC cell lines (MDA-MB-468, SUM-159PT, SUM-149PT, MDA-MB-231), were assessed. Results: The results showed that TNBC cells were more highly sensitive, in a dose-dependent manner, to PAM treatment. PAM selectively caused apoptosis of TNBC cell lines compared to luminal lines and had little effect on the normal cell lines. It has been hypothesised that the cancer-selective CAP and PAM cytotoxicity is due in part to reactive oxygen (ROS) and nitrogen species (RNS). Constitutive RONS levels, combined with those present in and/or induced by PAM, can combine to push the cells over a cytotoxic threshold. In support of this, we found a tight correlation (R2=0.7502) between the constitutive ROS level of different cell lines used and their response (cell viability) to 100% PAM treatment, and found that ROS levels selectively increased further in the TNBC&amp;gt;luminal&amp;gt;normal cells in response to PAM. We have also identified a strong synergistic molecular partner that further promotes sensitivity and selectivity of PAM for TNBC cells. Conclusion: We demonstrated that treatment with PAM promotes apoptosis n cell lines representing the most aggressive TNBC subtype. This discovery opens new TNBC-selective opportunities for simultaneous inhibition of diverse (parallel) cancer development factors through synergistic interactions enabled through plasma activated biochemical media. Citation Format: Peiyu Wang, Renwu Zhou, Rusen Zhou, Jennifer Gunter, Fiona Simpson, Kostya (Ken) Ostrikov, Derek Richard, Xiaofeng Dai, Erik (Rik) Walter Thompson. Cold atmospheric plasma therapy selectively targets triple negative breast cancer cells [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 996.
Cell competition acts as a purifying selection to eliminate cells with mitochondrial defects during early mouse development
Authors: Ana Lima, Gabriele Lubatti, Jörg Burgstaller, Di Hu, Alistair P. Green, Aida Di Gregorio, Tamzin Zawadzki, Barbara Pernaute, Elmir Mahammadov, Salvador Perez-Montero, Marian Dore, Juan Miguel Sanchez, Sarah Bowling, Margarida Sancho, Thomas Kolbe, Mohammad M. Karimi, David Carling, Nick Jones, Shankar Srinivas, Antonio Scialdone, Tristan A. Rodriguez
Journal: Nature Metabolism (2021)
Hypersensitivity reactions in sporotrichosis: a retrospective cohort of 325 patients from a reference hospital in Rio de Janeiro, Brazil (2005–2018)
Authors: A.C. Procópio‐Azevedo, V.B.S. Rabello, M.M. Muniz, M.H.G. Figueiredo‐Carvalho, R. Almeida‐Paes, R.M. Zancopé‐Oliveira, J.C.A.L. Silva, P.M. Macedo, A.C.F. Valle, M.C. Gutierrez‐Galhardo, D.F.S. Freitas
Journal: British Journal of Dermatology (2021)
Abstract 117: Inhibition of Hedgehog signaling alters fibroblast composition in pancreatic cancer
Authors: Nina G. Steele, Giulia Biffi, Samantha Kemp, Yaqing Zhang, Donovan Drouillard, LiJyun Syu, Yuan Hao, Tobiloba Oni, Erin Brosnan, Ela Elyada, Abhishek Doshi, Christa Hansma, Carlos Espinoza, Ahmed Abbas, Stephanie The, Valerie Irizarry-Negron, Christopher Halbrook, Nicole Franks, Megan Hoffman, Eileen Carpenter, Zeribe Nwosu, Youngkyu Park, Howard Crawford, Costas Lyssiotis, Timothy Frankel, Arvind Rao, Filip Bednar, Andrzej Dlugosz, Jonathan Preall, David Tuveson, Benjamin Allen, Marina Pasca di Magliano
Journal: Cancer Research (2021)

Abstract Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease characterized by an extensive fibroinflammatory stroma, which includes abundant cancer-associated fibroblast (CAF) populations. PDAC CAFs are heterogeneous, but the nature of this heterogeneity is incompletely understood. The Hedgehog (HH) pathway functions in PDAC in a paracrine manner, with ligands secreted by cancer cells signaling to stromal cells in the microenvironment. Previous reports investigating the role of HH signaling in PDAC have been contradictory, with HH signaling alternately proposed to promote or restrict tumor growth. In light of the newly discovered CAF heterogeneity, we investigated how HH pathway inhibition reprograms the PDAC microenvironment. Experimental Design: We used a combination of pharmacologic inhibition, gain- and loss- of-function genetic experiments, CyTOF, and single cell RNA-sequencing to study the roles of HH signaling in PDAC. Results: We find that HH signaling is uniquely activated in fibroblasts and differentially elevated in myofibroblastic CAFs (myCAFs) compared to inflammatory CAFs (iCAFs). SHH overexpression promotes tumor growth, while HH pathway inhibition with the Smoothened antagonist LDE225 impairs tumor growth. Further, HH pathway inhibition reduces myCAF numbers and increases iCAF numbers, which correlates with a decrease in cytotoxic T cells and an expansion in Tregs, consistent with increased immune suppression. Conclusions: HH pathway inhibition alters fibroblast composition and immune infiltration in the pancreatic cancer microenvironment. Citation Format: Nina G. Steele, Giulia Biffi, Samantha Kemp, Yaqing Zhang, Donovan Drouillard, LiJyun Syu, Yuan Hao, Tobiloba Oni, Erin Brosnan, Ela Elyada, Abhishek Doshi, Christa Hansma, Carlos Espinoza, Ahmed Abbas, Stephanie The, Valerie Irizarry-Negron, Christopher Halbrook, Nicole Franks, Megan Hoffman, Eileen Carpenter, Zeribe Nwosu, Youngkyu Park, Howard Crawford, Costas Lyssiotis, Timothy Frankel, Arvind Rao, Filip Bednar, Andrzej Dlugosz, Jonathan Preall, David Tuveson, Benjamin Allen, Marina Pasca di Magliano. Inhibition of Hedgehog signaling alters fibroblast composition in pancreatic 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 117.
Abstract 1226: Targeting OSCC fitness genes YAP1 and WWTR1 via synergistic killing of CA3 in combination with cisplatin
Authors: Annie Wai Yeeng Chai, Pei San Yee, Shi Mun Yee, Sok Ching Cheong
Journal: Cancer Research (2021)

Abstract Oral squamous cell carcinoma (OSCC) is one of the most common forms of head and neck cancer, with more than half of the global mortality occurring in Asia. The current treatment regimens for OSCC are of limited benefit to the patients and the development of new targeted therapies is very much needed. In our previous study using genome-wide CRISPR/Cas9 screen to identify the genetic vulnerabilities for OSCC, we have successfully identified two key fitness genes - YAP1 and WWTR1 (TAZ) of the Hippo signaling pathway as potential therapeutic targets for OSCC. We discovered that CRISPR/Cas9-mediated knockout of either YAP1 or WWTR1 in the YAP1- or WWTR1-dependent OSCC cell lines resulted in the down-regulation of pro-proliferative genes such as the CTGF and CYR61. Further, both YAP1 and WWTR1 have separately been implicated as potential mediators of resistance to cisplatin, a common chemotherapy used for the treatment of OSCC patients. Inhibition of the interaction between either YAP1 or WWTR1 with their downstream binding partners, such as the transcription factor, TEAD, has been one of the main focus for therapeutic intervention. However, this has not been examined in the context of OSCC. We, therefore, aim to i) identify and evaluate the anti-proliferative effect of existing YAP1/WWTR1 inhibitors on YAP1/WWTR1-dependent OSCC, ii) evaluate the synergistic effect of combining the YAP1/WWTR1 inhibitors with cisplatin in controlling OSCC growth. We identify two putative inhibitors of YAP/WWTR1/TEAD - Verteporfin and CA3. We show that compared to Verteporfin, the new inhibitor, CA3 exerts a more prominent anti-proliferative effect on the OSCC models that are dependent on either YAP1 or WWTR1, with IC50 in the nanomolar range. We then test the effect of combining CA3 (at 0.5µM and 1µM) with various dosages of cisplatin and demonstrated strong synergistic effects in OSCC across most combinations. We show that CA3 sensitizes OSCC cells to cisplatin at concentrations as low as 0.5µM. Our results further confirm that YAP1/TAZ are important therapeutic targets in OSCC and the treatment of YAP1/TAZ inhibitors could sensitize the OSCC cells to cisplatin. Further investigation is warranted to uncover the mechanism underlying YAP/TAZ-mediated cisplatin sensitivity in OSCC to improve the proportion of OSCC patients who could respond to cisplatin. Citation Format: Annie Wai Yeeng Chai, Pei San Yee, Shi Mun Yee, Sok Ching Cheong. Targeting OSCC fitness genes YAP1 and WWTR1 via synergistic killing of CA3 in combination with cisplatin [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 1226.
Abstract 2222: The molecular landscape of acral lentiginous melanoma in Mexican patients
Authors: Martha E. Vázquez-Cruz, Patricia Basurto-Lozada, Christian Molina-Aguilar, Carolina Castaneda-Garcia, Ingrid Ferreira, Héctor Martínez-Said, Alethia Álvarez-Cano, Luis Alberto Tavares-de la Paz, Diego Hinojosa-Ugarte, Dorian Y. García-Ortega, Julia M. Martínez-Gómez, Mitchell P. Levesque, David J. Adams, Carla D. Robles-Espinoza
Journal: Cancer Research (2021)

Abstract Acral lentiginous melanoma (ALM) is the most common melanoma subtype in several countries in Africa, Asia, and Latin America, including Mexico. Comparatively fewer studies have been published of ALM than other subtypes of the disease. However, it is becoming clear that complex DNA structural aberrations, as well as several genes, such as NOTCH2, KIT, PTEN and TYRP1, in addition to the established melanoma drivers, play a role in its development. To date, no comprehensive genomic characterization has been performed on tumors from Latin American patients. The causes of ALM are unknown, and little is known about its transcriptomic profile and immune landscape. Because of these factors, therapeutic options are limited, while approaches such as immunotherapy are too costly for most patients in Latin American countries, and are of unknown efficacy in rarer forms of melanoma such as ALM. A better understanding of the molecular and immune profile of ALM would allow us to identify potential therapeutic targets and treatment strategies in this population. We have sequenced the exomes and transcriptomes of 113 ALM tumors (primaries, metastases and recurrences) from 86 patients being treated at the National Cancer Institute of Mexico, a national reference hospital. We have performed analyses to define the genomic landscape of the disease, its mutational signatures, the biological pathways involved in its development, and its immune profile. From these analyses, we have identified recurrently amplified and deleted genomic regions, potential causal agents, and the involvement of specific interleukins and cell-adhesion proteins in ulcerated and metastatic tumors. This study is one of the first to profile the molecular landscape of ALM in a Latin American population. We hope that it will contribute to increasing the diversity of cancer genomics datasets, help highlight differences in disease biology, and provide insights that may inform therapeutic strategies for all patients with this lethal malignancy. Citation Format: Martha E. Vázquez-Cruz, Patricia Basurto-Lozada, Christian Molina-Aguilar, Carolina Castaneda-Garcia, Ingrid Ferreira, Héctor Martínez-Said, Alethia Álvarez-Cano, Luis Alberto Tavares-de la Paz, Diego Hinojosa-Ugarte, Dorian Y. García-Ortega, Julia M. Martínez-Gómez, Mitchell P. Levesque, David J. Adams, Carla D. Robles-Espinoza. The molecular landscape of acral lentiginous melanoma in Mexican 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 2222.
PAI-1遺伝子発現の低酸素誘導を媒介する内皮PAS-1(EPAS1):腫瘍脈管形成におけるEPAS1の潜在的役割
Authors: Sato M, Tanaka T, Akiyama H, Uchiyama T, Kurabayashi M
Journal: Circulation (2000)
Clonal Architecture of TET2 Mutations Influences the Clinical Phenotype of Patients with Myeloid Neoplasms
Authors: Cassandra M. Hirsch, Aziz Nazha, Kneen Kassy, Manja Meggendorfer, Bartlomiej P. Przychodzen, Niroshan Nadarajah, Vera Adema, Yasunobu Nagata, Valeria Visconte, Hetty E. Carraway, Mikkael A. Sekeres, Ryszard Ólinski, Sudipto Mukherjee, Babal K Jha, Thomas Laframboise, Tomas Radivoyevitch, Torsten Haferlach, Jaroslaw P. Maciejewski
Journal: Blood (2017)
Early PDD cystoscopy after BCG induction for high-risk non-muscle invasive bladder cancer significantly increased the detection of BCG-refractory tumors
Authors: M. Morelli, M. Baboudjian, R. Boissier, D. Vanacore, G. Karsenty, E. Montanari, E. Lechevallier
Journal: European Urology (2021)
Interleukin-5-induced eosinophil population improves cardiac function after myocardial infarction
Authors: Jun Yan Xu, Yu Yan Xiong, Rui Jie Tang, Wen Yang Jiang, Yu Ning, Zhao Ting Gong, Pei Sen Huang, Gui Hao Chen, Jun Xu, Chun Xiao Wu, Meng Jin Hu, Jing Xu, Yi Xu, Cun Rong Huang, Chen Jin, Xiao Tong Lu, Hai Yan Qian, Xiang Dong Li, Yue Jin Yang
Journal: Cardiovascular Research (2021)

Abstract Aims Interleukin (IL)-5 mediates the development of eosinophils (EOS) that are essential for tissue post-injury repair. It remains unknown whether IL-5 plays a role in heart repair after myocardial infarction (MI). This study aims to test whether IL-5-induced EOS population promotes the healing and repair process post-MI and to reveal the underlying mechanisms. Methods and results MI was induced by permanent ligation of the left anterior descending coronary artery in wild-type C57BL/6 mice. Western blot and real-time polymerase chain reaction revealed elevated expression of IL-5 in the heart at 5 days post-MI. Immunohistostaining indicated that IL-5 was secreted mainly from macrophages and CD127+ cells in the setting of experimental MI. External supply of recombinant mouse IL-5 (20 min, 1 day, and 2 days after MI surgery) reduced the infarct size and increased ejection fraction and angiogenesis in the border zone. A significant expansion of EOS was detected in both the peripheral blood and infarcted myocardium after IL-5 administration. Pharmacological depletion of EOS by TRFK5 pretreatment muted the beneficial effects of IL-5 in MI mice. Mechanistic studies demonstrated that IL-5 increased the accumulation of CD206+ macrophages in infarcted myocardium at 7 days post-MI. In vitro co-culture experiments showed that EOS shifted bone marrow-derived macrophage polarization towards the CD206+ phenotypes. This activity of EOS was abolished by IL-4 neutralizing antibody, but not IL-10 or IL-13 neutralization. Western blot analyses demonstrated that EOS promoted the macrophage downstream signal transducer and activator of transcription 6 (STAT6) phosphorylation. Conclusion IL-5 facilitates the recovery of cardiac dysfunction post-MI by promoting EOS accumulation and subsequent CD206+ macrophage polarization via the IL-4/STAT6 axis.
Abstract 2788: Deep characterization of tumor infiltrating leukocytes using a combination of flow cytometry and single-cell multiomics
Authors: Xiaoshan Shi, Margaret Nakamoto, Aaron Middlebrook, Wei Huang, Evelyn Lo, Patrick T. Neuhoefer, Scott Bornheimer, Smita Ghanekar
Journal: Cancer Research (2021)

Abstract Cancer immunotherapies have the potential to induce durable anti-tumor immune responses; however the efficacy of these treatments varies among patients and partially depends on the complex interplay between malignant cells and non-malignant cells within the tumor microenvironment. In the tumor microenvironment, T cells play a crucial role in eliminating tumor cells and orchestrating anti-tumor immune responses; in contrast immunosuppressive cell types such as myeloid-derived suppressor cells can support tumor progression. Here we harnessed recent advances in single-cell multiomics that allow high-resolution functional characterization of intratumoral immune cells to improve our understanding of their dynamic relationships. Specifically, we utilized a One Solution Workflow to dissociate a solid tumor followed by in-depth dissection of the immune composition of the tumor microenvironment using both flow cytometry and the BD Rhapsody™ Single-Cell Analysis System. We characterized the cellular composition of tumor microenvironment using flow cytometry analysis. Importantly, by examining the expression of mRNA and surface protein markers at single-cell resolution, we unraveled the complexities of the tumor microenvironment, elucidated cellular heterogeneity and identified cell-type specific gene signatures. We propose this One Solution Workflow can be adopted to understand the transcriptional and proteomic phenotypes of tumor infiltrating leukocytes for development of novel immune therapeutic strategies for cancer. For Research Use Only. Not for use in diagnostic or therapeutic procedures. Class 1 Laser Product.BD-23279 (v1.0) 1120BD, the BD Logo and Rhapsody are trademarks of Becton, Dickinson and Company or its affiliates. © 2020 BD. All rights reserved. Citation Format: Xiaoshan Shi, Margaret Nakamoto, Aaron Middlebrook, Wei Huang, Evelyn Lo, Patrick T. Neuhoefer, Scott Bornheimer, Smita Ghanekar. Deep characterization of tumor infiltrating leukocytes using a combination of flow cytometry and single-cell multiomics [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 2788.
Abstract 1434: Uncovering the mechanism of adaptive resistance to RET inhibitors in RET rearranged thyroid cancer
Authors: Renuka Raman, Jacques Villefranc, Timothy Ullmann, Jessica Thiesmeyer, Viviana Anelli, Chantal Pauli, Rohan Bareja, Kenneth Wha Eng, Princesca Dorsaint, David Wilkes, Shaham Beg, Reid Shaw, Michael Churchill, Naveen Gumpeni, Theresa Scognamiglio, Mark Rubin, Carla Grandori, Juan Mosquera, Juan Mosquera, Juan Mosquera, Noah Dephoure, Andrea Sboner, Olivier Elemento, Yariv Houvras
Journal: Cancer Research (2021)

Abstract Kinase inhibitors are a critical tool for cancer treatment, but their efficacy is limited by resistance mechanisms. In thyroid and lung cancer RET gene rearrangements result in constitutive MAPK pathway activation and drive malignancy. While treatment with new selective RET inhibitors has been associated with significant clinical responses, a majority of patients experience a partial response or disease stabilization as their best clinical outcome. Resistance to RET inhibitors has emerged as a clinical problem requiring new treatment strategies. Using a combination of drug screening, proteomic, and biochemical profiling we identified a strategy to overcome adaptive resistance to RET inhibitors in human thyroid cancer cell lines and vertebrate animal models. The identification of alternative signaling pathways that reactivates ERK signaling as a mechanism of resistance to RET inhibitors provides an opportunity to anticipate resistance to selective RET inhibitors and use combination therapy that leads to more significant and durable anti-tumor responses in patients with RET rearranged cancers. Citation Format: Renuka Raman, Jacques Villefranc, Timothy Ullmann, Jessica Thiesmeyer, Viviana Anelli, Chantal Pauli, Rohan Bareja, Kenneth Wha Eng, Princesca Dorsaint, David Wilkes, Shaham Beg, Reid Shaw, Michael Churchill, Naveen Gumpeni, Theresa Scognamiglio, Mark Rubin, Carla Grandori, Juan Mosquera, Juan Mosquera, Juan Mosquera, Noah Dephoure, Andrea Sboner, Olivier Elemento, Yariv Houvras. Uncovering the mechanism of adaptive resistance to RET inhibitors in RET rearranged thyroid 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 1434.
Abstract 2433: Core regulatory circuits of clear cell ovarian and kidney cancers
Authors: Marla Elizabeth Scott, Robbin Nameki, Forough Abbasi, Marcos Abraao de Souza Fonseca, Rosario (Ivetth) Corona de la Fuente, Kate Lawrenson
Journal: Cancer Research (2021)

Abstract Clear cell ovarian and kidney cancers are rare but aggressive cancers characterized by resistance to traditional chemotherapies. The transcriptional drivers of these tumors are poorly understood, but the histologic similarities suggest that a subset of common factors may drive differentiation of the clear cell phenotype, agnostic of anatomic origin. Master transcription factors (MTFs) are the essential transcriptional regulators that create interconnected auto-regulatory circuits critical for tumor cell survival. Candidate MTFs can be identified due to their characteristic high level, tissue-specific expression, functional essentiality in tumor models, and participation in interconnected core regulatory transcriptional circuits. We collated 5 high grade serous ovarian cancer, 5 clear cell ovarian cancer, 5 papillary renal cell cancer and 11 clear cell renal cell cancer primary tissue and 27 cell line data sets for clear cell ovarian and kidney cancers, and non-clear cell tumors of the same organs. We integrated gene expression, super-enhancer landscapes and global maps of open chromatin to identify candidate MTFs specific to clear cell tumors. This identified known Hepatocyte nuclear factor-1-beta (HNF1B), commonly over-expressed in &amp;gt;90% of clear cell cancers and other novel candidates, including RARA, which encodes retinoic acid receptor alpha. Clear cell kidney and ovarian cancer cell lines are often co-dependent on sustained expression of HNF1B and RARA for survival, suggesting perturbed retinoic acid signaling represents a novel therapeutic target for clear cell tumors. Transcriptional inhibitors provide a novel therapeutic target for many cancers that may otherwise be chemoresistant. Clear cell lines are particularly sensitive to general transcriptional inhibitors in in-vitro models; functional analyses are ongoing to determine the role of RARA, HNF1B and other factors in explaining these responses. Citation Format: Marla Elizabeth Scott, Robbin Nameki, Forough Abbasi, Marcos Abraao de Souza Fonseca, Rosario (Ivetth) Corona de la Fuente, Kate Lawrenson. Core regulatory circuits of clear cell ovarian and kidney cancers [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 2433.