tbuckley/cabot-search huggingface dataset:
Acquired resistance to anti-MAPK targeted therapy confers an immune-evasive tumor microenvironment and cross-resistance to immunotherapy in melanoma
Authors: Lisa Haas, Anais Elewaut, Camille L. Gerard, Christian Umkehrer, Lukas Leiendecker, Malin Pedersen, Izabela Krecioch, David Hoffmann, Maria Novatchkova, Mario Kuttke, Tobias Neumann, Ines Pires da Silva, Harriet Witthock, Michel A. Cuendet, Sebastian Carotta, Kevin J. Harrington, Johannes Zuber, Richard A. Scolyer, Georgina V. Long, James S. Wilmott, Olivier Michielin, Sakari Vanharanta, Thomas Wiesner, Anna C. Obenauf
Journal: Nature Cancer (2021)
Abstract 2611: Transcription factor-nucleosome dynamics inferred from plasma cfDNA delineates tumor and tumor-microenvironment phenotype
Authors: Satyanarayan Rao, Amy Han, Alexis Zukowski, Etana Kopin, Peter Kabos, Srinivas Ramachandran
Journal: Cancer Research (2021)

Abstract Our current understanding of solid tumors and their progression primarily relies on in vitro models, cell lines, patient-derived xenografts, and scarce data from invasive tissue biopsies from patients. The ability to monitor changes in chromatin structure and transcription factor binding in tumor cells using a minimally invasive approach in humans has the potential to revolutionize our understanding of disease progression and treatment resistance. In this study, we use the example of estrogen receptor (ER) positive breast cancer, the most common disease subtype, and define the ER axis from plasma cell-free DNA (cfDNA). While lymphoid/myeloid cell turnover represents the dominant source of cfDNA in the bloodstream, a detectable fraction of DNA from tumor tissue-of-origin can be found in patients with solid cancers. cfDNA is the product of the action of endogenous nucleases on chromatin; and retains the map of epigenomes from cells of origin. Our method therefore non-invasively captures TF-nucleosome dynamics in tumor tissue-of-origin using plasma cfDNA. First, we show that we can reliably identify the active binding of hematopoietic pioneer factor PU.1 and CTCF from cfDNA of healthy humans and cancer patients. Then to define cfDNA binding of disease specific TF ER, we used ER+ patient-derived xenograft (PDX) models allowing for a clear separation of tumor signal from hematopoietic background. This allowed us to establish the sensitivity and specificity of our approach. We also identified the subset of CUT&amp;RUN-defined ER binding sites that feature the strongest binding in vivo from both lymphocyte background as well as cancer cells. Furthermore, we can define the active binding sites of pioneer factor FOXA1, which facilitates ER binding by opening the chromatin. Based on the TF protection levels from cfDNA we were able to define tumor as well as hematopoietic-specific TF binding sites that can serve as potential hotspots to monitor ER+ disease state at around 1% tumor fraction. These data demonstrate our ability to simultaneously monitor TF and nucleosome dynamics at disease sites just from plasma that can enable real-time monitoring of disease phenotype in a minimally invasive manner. Citation Format: Satyanarayan Rao, Amy Han, Alexis Zukowski, Etana Kopin, Peter Kabos, Srinivas Ramachandran. Transcription factor-nucleosome dynamics inferred from plasma cfDNA delineates tumor and tumor-microenvironment phenotype [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 2611.
小児におけるフィラデルフィア染色体陽性急性リンパ芽球性白血病(Ph+ALL)のための同種間の幹細胞移植(SCT):東京小児がん研究グループ(TCCSG)研究L95-14
Authors: Manabe A, Toyoda Y, Ikuta K, Hanada R, Yabe H, Kinoshita A, Koike K, Okimoto Y, Noguchi Y, Kajiwara, Uchiyama H, Kumagai M, Sugita Kj, Isoyama K, Hayashi Y, Ishimoto K, Kikuchi A, Saito T, Tsuchida M, Nakazawa S
Journal: Blood (2000)
Fluid Dynamics of Respiratory Infectious Diseases
Authors: Lydia Bourouiba
Journal: Annual Review of Biomedical Engineering (2021)

The host-to-host transmission of respiratory infectious diseases is fundamentally enabled by the interaction of pathogens with a variety of fluids (gas or liquid) that shape pathogen encapsulation and emission, transport and persistence in the environment, and new host invasion and infection. Deciphering the mechanisms and fluid properties that govern and promote these steps of pathogen transmission will enable better risk assessment and infection control strategies, and may reveal previously underappreciated ways in which the pathogens might actually adapt to or manipulate the physical and chemical characteristics of these carrier fluids to benefit their own transmission. In this article, I review our current understanding of the mechanisms shaping the fluid dynamics of respiratory infectious diseases.
Abstract 2416: Upregulation of amplified in breast cancer 1 contributes to pancreatic ductal adenocarcinoma progression and vulnerability to blockage of hedgehog activation
Authors: Licen Li, Jiaolin Bao, Haitao Wang, Haipeng Lei, Peng Cheng, Jianming Zeng, Wenhui Hao, Xu Zhang, Xiaoling Xu, Chundong Yu, Chu-Xia Deng, Qiang Chen
Journal: Cancer Research (2021)

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and devastating cancers without effective treatments. Amplified in breast cancer 1 (AIB1) is a member of the steroid receptor coactivator family that mediates the transcriptional activities of nuclear receptors. While AIB1 is associated with the initiation and progression of multiple cancers, the mechanism by which AIB1 contributes to PDAC progression remains largely unknown. In this study, we aimed to explore the role of AIB1 in the progression of PDAC and elucidate the underlying mechanisms. Methods: The clinical significance and mRNA level of AIB1 in PDAC were studied by database analysis. To demonstrate whether AIB1 mediates the malignant features of PDAC cells, namely, proliferation, migration, invasion, we performed real-time PCR and Western blot analysis, established xenograft models and used in vivo metastasis assay. With insights into the mechanism of AIB1, we performed RNA sequencing (Seq), ChIP-Seq, luciferase reporter assays and pull-down assays. Furthermore, we analyzed the relationship between AIB1 expression and its target expression in PDAC cells and patients and explored whether PDAC cells with high AIB1 levels are sensitive to inhibitors of its target. Results: We found that AIB1 was significantly upregulated in PDAC and associated with its malignancy. Silencing AIB1 impaired hedgehog (Hh) activation by reducing the expression of smoothened (SMO), leading to cell cycle arrest and the inhibition of PDAC cell proliferation. In addition, AIB1, via upregulation of integrin αv (ITGAV) expression, promoted extracellular matrix (ECM) signaling, which played an important role in PDAC progression. Further studies showed that AIB1 preferably bound to AP-1 related elements and served as a coactivator for enhancing the transcriptional activity of MafB, which promoted the expression of SMO and ITGAV. PDAC cells with high AIB1 levels were sensitive to Hh signaling inhibitors, suggesting that blocking Hh activation is an effective treatment against PDAC with high AIB1 expression. Conclusions: These findings reveal that AIB1 is a crucial oncogenic regulator associated with PDAC progression via Hh and ECM signaling and suggest potential therapeutic targets for PDAC treatment. Citation Format: Licen Li, Jiaolin Bao, Haitao Wang, Haipeng Lei, Peng Cheng, Jianming Zeng, Wenhui Hao, Xu Zhang, Xiaoling Xu, Chundong Yu, Chu-Xia Deng, Qiang Chen. Upregulation of amplified in breast cancer 1 contributes to pancreatic ductal adenocarcinoma progression and vulnerability to blockage of hedgehog activation [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 2416.
Lactobacillus vaginal suppositories for recurrent cystitis: A phase 2 clinical trial
Authors: T. Sadahira, K. Wada, A. Ishii, Y. Maruyama, T. Iwata, K. Yoshinaga, T. Sekito, M. Araki, T. Watanabe, Y. Nasu
Journal: European Urology (2021)
Abstract 2540: Belief in research, religious coping, and willingness to participate in clinical trials among African Americans with hematologic malignancies: a pilot study
Authors: Marjorie Petty
Journal: Cancer Research (2021)

Abstract Purpose: The purpose of the proposed prospective cohort, pilot study is to recruit 30 AAs with hematologic malignancies to determine if a relationship exists between belief in research and willingness to participate in cancer clinical trials. The secondary objective is to determine whether religious coping moderates the effect of belief in research on the relationship between willingness to participate. Description: African Americans (AAs) are disproportionately affected by certain types of hematologic malignancies, yet despite the efforts of investigators, they remain grossly underrepresented in cancer clinical trials. Few studies have evaluated the underrepresentation in clinical trials in this subgroup, while studies evaluating the same problem in AAs with solid tumors is well documented. A known barrier to clinical trial enrollment is knowledge of clinical trials; however, knowledge does not necessarily mean one will participate. One has also to believe and be willing to participate in clinical trials. Even so, it is unknown if a relationship exists between belief in research and willingness to participate in clinical trials in AAs with hematologic malignancies. Similarly, it is unknown if religious coping influences the possible association between belief in research and willingness to participate in AAs with hematologic malignancies. Due to sparse literature showing the connection of the concepts within this subset of AAs, research investigating the relationship between belief in research and willingness to participate is warranted. Summary: Data will be captured at one time using the validated Brief Religious Coping Scale and researcher generated questions that address belief in research and willingness to participate in cancer clinical trials. Conclusion: Findings will help in the design of future studies and the feasibility of recruiting AAs with hematologic malignancies. Citation Format: Marjorie Petty. Belief in research, religious coping, and willingness to participate in clinical trials among African Americans with hematologic malignancies: a pilot study [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 2540.
Global Genetic Heterogeneity in Adaptive Traits
Authors: William Andres Lopez-Arboleda, Stephan Reinert, Magnus Nordborg, Arthur Korte
Journal: Molecular Biology and Evolution (2021)

Understanding the genetic architecture of complex traits is a major objective in biology. The standard approach for doing so is genome-wide association studies (GWAS), which aim to identify genetic polymorphisms responsible for variation in traits of interest. In human genetics, consistency across studies is commonly used as an indicator of reliability. However, if traits are involved in adaptation to the local environment, we do not necessarily expect reproducibility. On the contrary, results may depend on where you sample, and sampling across a wide range of environments may decrease the power of GWAS because of increased genetic heterogeneity. In this study, we examine how sampling affects GWAS in the model plant species Arabidopsis thaliana. We show that traits like flowering time are indeed influenced by distinct genetic effects in local populations. Furthermore, using gene expression as a molecular phenotype, we show that some genes are globally affected by shared variants, whereas others are affected by variants specific to subpopulations. Remarkably, the former are essentially all cis-regulated, whereas the latter are predominately affected by trans-acting variants. Our result illustrate that conclusions about genetic architecture can be extremely sensitive to sampling and population structure.
Abstract 2650: Angiogenic inhibitors reduce mycosis fungoides cell survival and enhance cell death
Authors: Natalia Rendon-Serna, Maeva Dufies, Luis Alfonso Correa-Londono, Olga Maria Bermudez-Munoz, Margarita Maria Velasquez-Lopera, Gilles Pages
Journal: Cancer Research (2021)

Abstract Cutaneous T-cell lymphomas (CTCL) account for approximately 80% of cases of cutaneous lymphomas. Among CTCL, mycosis fungoides (MF) is the most common and most studied type comprising up to 55% of cases. Three different MF stages are recognized in the following order of pathology evolution: patches, plaques and tumor; MF can progress to tumor stage with involvement of other organs, compromising life due to systemic malignant invasion and immunosuppression. Currently, there are not long-lasting treatment for MF. We aimed to understand if angiogenesis, involved in solid tumor progression, could be involved in MF course. For this, we studied both, MF cell lines (HH, Myla) and skin tissues from MF patients at its different stages including healthy skin, according to ethical approval statements. We evaluated the density of blood vessels in skin from MF patients using staining for CD31 by immunohistochemistry. In HH and Myla cell lines, we have studied the presence of angiogenic receptors by western blot and then we have analyzed the effect of 3 angiogenic inhibitors, axitinib, cabozantinib and sunitinib, on cell survival and cell death. We found that there is an increased number of blood vessels in tumor stage compared with patch stage and healthy skin, and in plaque stage compared with patch stage. In HH and Myla cells that express VEGR2 and c-MET, we noticed that although they are sensitive to the angiogenic inhibitors used, axitinib and specially sunitinib reduced significantly cell survival and enhanced cell death at doses between 5-10 micromolar, at 72 hours. We conclude that the density of blood vessels increases with MF progression and thus that angiogenesis takes place during MF pathophysiology. Furthermore, the fact that angiogenic inhibitors already used in tumor treatment provoke MF cell death and affect MF cell survival, suggests that the use of angiogenic inhibitors could be of great interest for controlling MF progression. Future animal model experiments and clinical trials should reveal the potential of angiogenesis inhibition as a new therapeutical option for MF treatment. Citation Format: Natalia Rendon-Serna, Maeva Dufies, Luis Alfonso Correa-Londono, Olga Maria Bermudez-Munoz, Margarita Maria Velasquez-Lopera, Gilles Pages. Angiogenic inhibitors reduce mycosis fungoides cell survival and enhance cell death [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 2650.
Abstract 989: Tetraarsenic hexoxide enhances generation of mitochondrial ROS to promote pyroptosis by inducing the activation of caspase-3/GSDME in triple-negative breast cancer cells
Authors: Haein An, Jin Sun Heo, Akira Ooshima, Zhaoyan Wu, Seong-Jin Kim, ILLJU BAE, Kyung-Min Yang
Journal: Cancer Research (2021)

Abstract Modified arsenic derivative compounds such as arsenic trioxide (As2O3), arsenic trisulfide (As2S3), and tetraarsenic hexoxide (As4O6) have been known to be one of the potent anti-cytotoxic effects in various cancer cells, including leukemia, glioma, colon, breast, and cervix cancer cells. Particularly, tetraarsenic hexoxide was developed as a chemotherapeutic agent for patients with advanced cancers. Although anti-cancer effect of tetraarsenic hexoxide has been extensively studied in various cancer cells, the molecular basis of its tumor inhibitory activity remains poorly understood. In this study, we suggest a mechanism of tetraarsenic hexoxide induces pyroptosis through the increase of mitochondrial ROS by targeting phosphorylation of mitochondrial STAT3, subsequently activating caspase-3/GSDME that eventually leads to suppression of cancer progression of TNBC cells. Interestingly, we first found that tetraarsenic hexoxide markedly induced pyroptotic cell death through caspase-3 in releading N-terminal fragments of GSDME in TNBC cells. Indeed, tetraarsenic hexoxide-treated TNBC cells exhibited pyroptotic cell death and the release of LDH. Supporting this observation, inhibition of active caspase-3 attenuated tetraarsenic hexoxide-induced pyroptotic features by blocking the cleavage of GSDME. In conclusion, our results suggest a mechanism of tetraarsenic hexoxide by inducing pyroptosis through the increase of mitochondrial ROS by targeting phosphorylation of mitochondrial STAT3, subsequently activating caspase-3/GSDME that eventually leads to suppression of cancer progression of TNBC cells. Also, given that traditional chemotherapeutic agents, tetraarsenic hexoxide may be useful for aggressive TNBC cells showing resistance to apoptosis as a new GSDME-targeted therapeutic strategy. Citation Format: Haein An, Jin Sun Heo, Akira Ooshima, Zhaoyan Wu, Seong-Jin Kim, ILLJU BAE, Kyung-Min Yang. Tetraarsenic hexoxide enhances generation of mitochondrial ROS to promote pyroptosis by inducing the activation of caspase-3/GSDME in 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 989.
Paternal age affects the performance of EAU guidelines for genetic testing in infertile men: Implications for candidate selection
Authors: E. Ventimiglia, L. Boeri, E. Pozzi, F. Belladelli, G. Fallara, L. Candela, P. Capogrosso, N. Schifano, D. Cignoli, G. Colandrea, M. Raffo, J. Cornelius, A. Mattei, C. Abbate, F. Montorsi, A. Salonia
Journal: European Urology (2021)
An inflammatory aging clock (iAge) based on deep learning tracks multimorbidity, immunosenescence, frailty and cardiovascular aging
Authors: Nazish Sayed, Yingxiang Huang, Khiem Nguyen, Zuzana Krejciova-Rajaniemi, Anissa P. Grawe, Tianxiang Gao, Robert Tibshirani, Trevor Hastie, Ayelet Alpert, Lu Cui, Tatiana Kuznetsova, Yael Rosenberg-Hasson, Rita Ostan, Daniela Monti, Benoit Lehallier, Shai S. Shen-Orr, Holden T. Maecker, Cornelia L. Dekker, Tony Wyss-Coray, Claudio Franceschi, Vladimir Jojic, François Haddad, José G. Montoya, Joseph C. Wu, Mark M. Davis, David Furman
Journal: Nature Aging (2021)
Generation and Characterization of Novel VLA-4 Inhibitors for Stem Cell Mobilization in Combination with a CXCR2 Agonist
Authors: Moses O. Evbuomwan, Richard F Heier, Darja Karpova, Stephanie Christ, Ezhilarasi Chendamarai, Michael P Rettig, Linda G Eissenberg, Stacy D Arnett, Julie Ritchey, Marvin J Meyers, Peter G Ruminski, David W Griggs, Dwight Morrow, John F DiPersio
Journal: Blood (2017)
Abstract 2160: Tumor suppressor p53 down-regulates programmed cell death protein 4 (PDCD4) expression
Authors: Wei-Hsiung Yang, Andrew P. George, William H. Yang, Chiung-Min Wang, Richard H. Yang
Journal: Cancer Research (2021)

Abstract Programmed Cell Death Protein 4 (PDCD4), a well-known tumor suppressor, acts to inhibit translation initiation and cap-dependent translation by inhibiting the helicase activity of EIF4A. EIF4A tends to target mRNAs with structured 5'-UTR. PDCD4 can also prevent tumorigenesis by inhibiting tumor promoter-induced neoplastic transformation, and studies indicate that PDCD4 may inhibit translation of certain mRNAs via directly binding. A previous study has demonstrated that PDCD4 inhibits translation of p53 mRNA and treatment with DNA-damaging agents down-regulates PDCD4 expression but activates p53 expression. The study further demonstrated that treatment with DNA-damaging agents resulted in down-regulation of PDCD4 expression and an increase in p53 expression, suggesting a potential mechanism in which p53 regulates expression of Pdcd4. However, whether p53 directly regulates PDCD4 remains unknown. Herein, we demonstrate for the first time that p53 regulates PDCD4 expression. First, we found that overexpression of p53 in p53-null cells (H1299 and Saos2 cells) decreased PDCD4 protein level. Secondly, p53 dose-dependently decreased PDCD4 promoter activity in gene reporter assays. Moreover, we demonstrated that mutations on p53 (R273H: contact mutant, hotspot and R175H: conformational mutant, hotspot) abolished p53-mediated PDCD4 repression. Furthermore, using Tet-on expression system, PDCD4 protein level was decreased when WT p53, but not hotspot mutants of p53, was expressed in H1299 cells. Finally, mutations on DNA-binding domain, but not C-terminal regulatory domain, of p53 disrupted p53-mediated PDCD4 repression. Taken together, our results suggest that p53 functions as a novel regulator of PDCD4 and the relationship between of p53 and PDCD4 may be involved in tumor development and progression. Citation Format: Wei-Hsiung Yang, Andrew P. George, William H. Yang, Chiung-Min Wang, Richard H. Yang. Tumor suppressor p53 down-regulates programmed cell death protein 4 (PDCD4) expression [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 2160.