tbuckley/cabot-search huggingface dataset:
Chromosome aberrations, DNA damage signaling and chemosensitivity induced by the anticancer agent, irofulven
Authors: Weixin Wang, Timothy Wiltshire, Yutian Wang, Sharon L. Wenger, Emily S. Van Laar, Stephen J. Waters, Eddie Reed
Journal: Cancer Research (2005)

602  Irofulven (6-hydroxymethylacylfulvene) is one of a new class of anticancer agents that are semi-synthetic derivatives of the mushroom toxin illudin S. Preclinical studies and clinical trials have demonstrated that irofulven is effective against multiple tumor types. While mechanism of action studies suggest that irofulven induces DNA damage, ATM-dependent CHK2 activation, which contributes to S-phase arrest, and apoptosis, little is known regarding the nature and structure of DNA damage caused by irofulven. In this study, the chromosome damage and DNA damage response induced by irofulven, and the correlation between DNA damage signaling and chemosensitivity were investigated. In ovarian cancer cell lines A2780 (p53 wildtype) and CAOV3 (p53 mutant) cells irofulven induces chromosome breaks, triradials and quadriradials as demonstrated by mitotic spreads, suggesting irofulven induces DNA interstrand cross-linking and double strand breaks. Similar chromosome alterations were observed in paired colon cancer cell lines HCT116 and HCT116 p53-/- after irofulven treatment. The mitotic index was unchanged or decreased in all cells after irofulven treatment, indicating that irofulven-induced DNA damage results in cell cycle arrest. More chromosome radial formations and breaks were observed in CAOV3 and HCT116 p53-/- cells than in A2780 and HCT116 cells, suggesting that chromosome aberrations induced by irofulven are related to p53 status. Activation of DNA damage signaling proteins by irofulven induced DNA damage was explored in ovarian cancer cell lines. Phosphorylation of SMC1, NBS1, BRCA1 and p53 was observed after irofulven treatment. Furthermore, immunofluorescent staining indicated that 53BP1 and BRCA1 formed foci at the irofulven-induced damaged sites. To investigate whether the activation of DNA damage signaling proteins might contribute to chemosensitivity, vector and BRCA1-transfected human breast cancer cell line HCC1937, which lacks functional BRCA1, were treated with irofulven. As demonstrated by the colonogenic survival assay, BRCA1 expression conferred increased resistance to irofulven treatment. This observation was further corroborated by increased sensitivity to irofulven observed after knocking down the BRCA1 protein level by RNA interference in SKOV3 cells. In summary, these results indicate that irofulven induces chromosome aberrations and activates important effector proteins of DNA damage response pathways. Among them, BRCA1 contributes to irofulven-induced chemosensitivity. These findings may have clinical implications for irofulven-based therapy given the fact that BRCA1 is frequently mutated in familial breast and ovarian cancers. These observations also suggest that enhanced antitumor activity of irofulven can be achieved by targeted therapy against mediators of the DNA damage-signaling pathway.
日本の慢性リンパ性白血病患者における偏った未変異ではないV(H)1-69遺伝子の使用
Authors: Yamane A, Koiso H, Mitsui T, Hashimoto Y, Maekawa I, Yokohama A, Takafumi M, Tsukamoto N, Murakami H, Nojima Y, Karasawa M
Journal: Blood (2003)
Posttraumatic Stress Disorder and Cardiovascular Disease
Authors: Christopher J. O’Donnell, Lisa Schwartz Longacre, Beth E. Cohen, Zahi A. Fayad, Charles F. Gillespie, Israel Liberzon, Gita A. Pathak, Renato Polimanti, Victoria Risbrough, Robert J. Ursano, Richard S. Vander Heide, Clyde W. Yancy, Viola Vaccarino, George Sopko, Murray B. Stein
Journal: JAMA Cardiology (2021)

Posttraumatic stress disorder (PTSD) is characterized by a persistent maladaptive reaction after exposure to severe psychological trauma. Traumatic events that may precipitate PTSD include violent personal assaults, natural and human-made disasters, and exposure to military combat or warfare. There is a growing body of evidence for associations of PTSD with major risk factors for cardiovascular disease (CVD), such as hypertension and diabetes, as well as with major CVD outcomes, such as myocardial infarction and heart failure. However, it is unclear whether these associations are causal or confounded. Furthermore, the biological and behavioral mechanisms underlying these associations are poorly understood. Here, the available evidence on the association of PTSD with CVD from population, basic, and genomic research as well as from clinical and translational research are reviewed, seeking to identify major research gaps, barriers, and opportunities in knowledge acquisition and technology as well as research tools to support and accelerate critical research for near-term and longer-term translational research directions. Large-scale, well-designed prospective studies, capturing diverse and high-risk populations, are warranted that include uniform phenotyping of PTSD as well as broad assessment of biological and behavioral risk factors and CVD outcomes. Available evidence from functional brain imaging studies demonstrates that PTSD pathophysiology includes changes in specific anatomical brain regions and circuits, and studies of immune system function in individuals with PTSD suggest its association with enhanced immune inflammatory activity. However, establishment of animal models and human tissue biobanks is also warranted to elucidate the potential causal connection of PTSD-induced brain changes and/or inflammation with CVD pathophysiology. Emerging large-scale genome-wide association studies of PTSD will provide an opportunity to conduct mendelian randomization studies that test hypotheses regarding the presence, magnitude, and direction of causal associations between PTSD and CVD outcomes. By identifying research gaps in epidemiology and genomics, animal, and human translational research, opportunities to better justify and design future interventional trials are highlighted that may test whether treatment of PTSD or underlying neurobiological or immune dysregulation may improve or prevent CVD risk or outcomes.
Abstract 2360: Identifying differentially expressed miRNAs in CRC stem cell subpopulations
Authors: Victoria A. Stark, Vignesh Viswanathan, Caroline O. Facey, Lynn M. Opdenaker, Bruce M. Boman
Journal: Cancer Research (2021)

Abstract Our research goal is to discover the molecular mechanisms behind tumor heterogeneity in CRC. We previously showed that CRCs contain multiple subpopulations of cancer stem cells (CSCs) which may explain the occurrence tumor heterogeneity and resistance to treatment. To determine how CSC sub-populations might arise, we are studying miRNA expression in CRC SCs. MicroRNAs are known to regulate SC phenotype and are found to be dysregulated in many cancers. Hypothesis: Tumor heterogeneity results from existence of multiple CSC subpopulations that are regulated by distinct miRNAs. Accordingly, we are using bioinformatics and miRNA profiling to identify miRNAs that target SC genes in CRCs. Indeed, our miRNA expression profiling of normal and malignant ALDH+ human colonic SCs showed that miRNA92a targets the SC gene LRIG1 and upregulation of miRNA92a leads to decreased LRIG1 expression. We also discovered that miRNA23b targets the SC gene LGR5 and miRNA23b is upregulated in ALDH+ CSCs. We have identified several other candidate miRNAs that are predicted to target CD166, ALDH1A1, BMI1, LRG5, and LRIG1 SC genes. We are currently in the process of validating whether these miRNAs contribute to emergence of specific CSC sub-populations in CRCs. Thus, identifying miRNAs that regulate CSC subpopulations should provide new strategies to modulate CSC composition in order to sensitize tumors to treatments. Citation Format: Victoria A. Stark, Vignesh Viswanathan, Caroline O. Facey, Lynn M. Opdenaker, Bruce M. Boman. Identifying differentially expressed miRNAs in CRC stem cell subpopulations [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 2360.
Which ultrasound or MRI characteristics demonstrate the highest diagnostic accuracy in identifying malignancy in males with indeterminate lesions of the testis? A systematic review
Authors: M. Ager, A. Salonia, J. Mayo De Castro, J. Donaldson, M.I. Omar, K. Dimitrpoulos, T. Tharakan, L. Boeri, F. Janisch, T. Muilwijk, R. Nijman, C. Radmayr, M.P. Laguna Pes, S. Minhas
Journal: European Urology (2021)
Skeletal muscle loss predicts oncological outcomes in T1HG patients treated with adjuvant intravesical BCG: Implications for decision-making?
Authors: F. Soria, M. Barale, D. D’Andrea, K.M. Gust, A. Giordano, G. Pizzuto, S. Mazzoli, M. De Bellis, B. Lillaz, S.F. Shariat, P. Gontero
Journal: European Urology (2021)
Proficiency based progression training versus the Halsted’s model for learning to perform a robotic vesico-urethral anastomosis on an avian tissue model: A prospective, randomized, multicenter, cross-specialty and blinded clinical trial
Authors: R. De Groote, S. Puliatti, M. Amato, E. Mazzone, G. Rossiello, R. Farihna, A. Paludo, P. Uvin, J. Decoene, T. Tuyten, M. D’Hondt, N. Hubert, C. Chatzopoulos, B. De Troyer, L. Desender, B. Van Cleynenbreugel, A. Mottrie, A. Gallagher
Journal: European Urology (2021)
Customizing local and systemic therapies for women with early breast cancer: the St. Gallen International Consensus Guidelines for treatment of early breast cancer 2021
Authors: H.J. Burstein, G. Curigliano, B. Thürlimann, W.P. Weber, P. Poortmans, M.M. Regan, H.J. Senn, E.P. Winer, M. Gnant, Stephan Aebi, Fabrice André, Carlos Barrios, Jonas Bergh, Herve Bonnefoi, Denisse Bretel Morales, Sara Brucker, Harold Burstein, David Cameron, Fatima Cardoso, Lisa Carey, Boon Chua, Eva Ciruelos, Marco Colleoni, Giuseppe Curigliano, Suzette Delaloge, Carsten Denkert, Peter Dubsky, Bent Ejlertsen, Florian Fitzal, Prudence Francis, Viviana Galimberti, Hebatallah Gamal El Din Mohamed Mahmoud, Judy Garber, Michael Gnant, William Gradishar, Bahadir Gulluoglu, Nadia Harbeck, Chiun-Sheng Huang, Jens Huober, Andre Ilbawi, Zefei Jiang, Steven Johnston, Eun Sook Lee, Sibylle Loibl, Monica Morrow, Ann Partridge, Martine Piccart, Philip Poortmans, Aleix Prat, Meredith Regan, Isabella Rubio, Hope Rugo, Emiel Rutgers, Felix Sedlmayer, Vladimir Semiglazov, Hans-Joerg Senn, Zhiming Shao, Tanja Spanic, Petra Tesarova, Beat Thürlimann, Sergei Tjulandin, Masakazu Toi, Maureen Trudeau, Nicholas Turner, Inez Vaz Luis, Giuseppe Viale, Toru Watanabe, Walter P. Weber, Eric P. Winer, Binghe Xu
Journal: Annals of Oncology (2021)
<i>California v. Texas</i> — Ending the Campaign to Undo the ACA in the Courts
Authors: Nicholas Bagley
Journal: New England Journal of Medicine (2021)

Interview with Prof. Nicholas Bagley on the Supreme Court's decision in California v. Texas (12:46)Download In June, the U.S. Supreme Court rejected what will probably be the last major case seeking to uproot the ACA. The Court's decision most likely marks an end to Republicans' efforts to achieve in the courts what they have been unable to achieve in Congress.
Health attacks and protection strategies during Gaza's Great March of Return: a mixed methods study using data from WHO's Surveillance System for Attacks on Healthcare
Authors: Walaa Shehada, Benjamin Bouquet, Juliana Nassar, Carolyn Briody, Nadia Alfarra, Henry V Doctor, Mahmoud Daher, Gerald Rockenschaub, Graham Kirkwood, Allyson Pollock, Hyo-Jeong Kim
Journal: The Lancet (2021)
Abstract 1993: Off-target effects of ultra-low dose dimethyl sulfoxide on targetable signaling events in lung cancer in vitro models
Authors: Elisa Baldelli, Mahalakshmi Subramanian, Abduljalil M. Alsubaie, Sara Baglivo, K A. Hodge, Fortunato Bianconi, Vienna Ludovini, Lucio Crino', Emanuel F. Petricoin, Mariaelena Pierobon
Journal: Cancer Research (2021)

Abstract Background: The identification of targetable alterations in cancer continues to offer novel opportunities to the drug discovery process. However, pre-clinical testing often requires solubilization of these drugs in cosolvents like dimethyl sulfoxide (DMSO). Using commercially available models commonly used for in vitro drug screening and pre-clinical testing, we explored the DMSO off-target effects on functional signaling networks, drug targets, and downstream substrates. Materials and Methods: Eight commercially available Non-Small Cell Lung Cancer (NSCLC) cell lines were incubated with three ultra-low concentrations of DMSO (0.0008%, 0.002%, and 0.004% v/v, respectively) for 5 min, as well as 1, 6 and 24 hours. Following incubation, expression and activation levels of 183 proteins were captured using Reverse Phase Protein Array (RPPA) technology, of which 134 were kinases and downstream substrates. Results: The DMSO effect was heterogenous across cell lines and varied based on multiple factors including: concentration, exposure time, and cell line. Of the 183 proteins measured, 88% were statistically significant at the highest DMSO concentration, followed by 81% and 67% at lower concentrations. Only 28 proteins were found statistically different in more than 5 cell lines indicating heterogenous response across models. pERK 1/2 T202/Y204 emerged as the most frequently affected node along with stress-induced response and mitogenic proteins. These cell line specific DMSO-induced alterations, may modulate response to targeted agents and chemotherapeutics. Conclusions: Ultra-low DMSO concentrations have broad and heterogenous effects on targetable signaling proteins which are model, time, and concentration dependent. As such, off-target effects need to be carefully evaluated in the design and implementation of pre-clinical drug screening and testing. Citation Format: Elisa Baldelli, Mahalakshmi Subramanian, Abduljalil M. Alsubaie, Sara Baglivo, K A. Hodge, Fortunato Bianconi, Vienna Ludovini, Lucio Crino', Emanuel F. Petricoin, Mariaelena Pierobon. Off-target effects of ultra-low dose dimethyl sulfoxide on targetable signaling events in lung cancer in vitro models [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 1993.
Precision oncology in AML: validation of the prognostic value of the knowledge bank approach and suggestions for improvement
Authors: Marius Bill, Krzysztof Mrózek, Brian Giacopelli, Jessica Kohlschmidt, Deedra Nicolet, Dimitrios Papaioannou, Ann-Kathrin Eisfeld, Jonathan E. Kolitz, Bayard L. Powell, Andrew J. Carroll, Richard M. Stone, Ramiro Garzon, John C. Byrd, Clara D. Bloomfield, Christopher C. Oakes
Journal: Journal of Hematology & Oncology (2021)

Recently, a novel knowledge bank (KB) approach to predict outcomes of individual patients with acute myeloid leukemia (AML) was developed using unbiased machine learning. To validate its prognostic value, we analyzed 1612 adults with de novo AML treated on Cancer and Leukemia Group B front-line trials who had pretreatment clinical, cytogenetics, and mutation data on 81 leukemia/cancer-associated genes available. We used receiver operating characteristic (ROC) curves and the area under the curve (AUC) to evaluate the predictive values of the KB algorithm and other risk classifications. The KB algorithm predicted 3-year overall survival (OS) probability in the entire patient cohort (AUCKB = 0.799), and both younger (< 60 years) (AUCKB = 0.747) and older patients (AUCKB = 0.770). The KB algorithm predicted non-remission death (AUCKB = 0.860) well but was less accurate in predicting relapse death (AUCKB = 0.695) and death in first complete remission (AUCKB = 0.603). The KB algorithm's 3-year OS predictive value was higher than that of the 2017 European LeukemiaNet (ELN) classification (AUC2017ELN = 0.707, p < 0.001) and 2010 ELN classification (AUC2010ELN = 0.721, p < 0.001) but did not differ significantly from that of the 17-gene stemness score (AUC17-gene = 0.732, p = 0.10). Analysis of additional cytogenetic and molecular markers not included in the KB algorithm revealed that taking into account atypical complex karyotype, infrequent recurrent balanced chromosome rearrangements and mutational status of the SAMHD1, AXL and NOTCH1 genes may improve the KB algorithm. We conclude that the KB algorithm has a high predictive value that is higher than those of the 2017 and 2010 ELN classifications. Inclusion of additional genetic features might refine the KB algorithm.
Potent antibody-mediated neutralization limits bacteriophage treatment of a pulmonary Mycobacterium abscessus infection
Authors: Rebekah M. Dedrick, Krista G. Freeman, Jan A. Nguyen, Asli Bahadirli-Talbott, Bailey E. Smith, Andrew E. Wu, Aaron S. Ong, Cheng Ting Lin, Lisa C. Ruppel, Nicole M. Parrish, Graham F. Hatfull, Keira A. Cohen
Journal: Nature Medicine (2021)
Abstract 3141: Evolution of core archetypal phenotypes in progressive high grade serous ovarian cancer
Authors: Aritro Nath, Patrick Cosgrove, Benjamin Copeland, Hoda Mirsafian, Elizabeth Christie, Lance Pflieger, Sumana Majumdar, Mihaela Cristea, Ernest Han, Stephen Lee, Edward Wang, Sian Fereday, Nadia Traficante, Ravi Salgia, Theresa Werner, Adam Cohen, Phillip Moos, Jeffrey Chang, David Bowtell, Andrea Bild
Journal: Cancer Research (2021)

Abstract The evolution of resistance in high-grade serous ovarian cancer (HGSOC) cells following chemotherapy is only partially understood. To uncover phenotypic changes associated with chemotherapy resistance, we profiled single-cell RNA-sequencing (scRNA-seq) transcriptomes of HGSOC tumors collected longitudinally during patient treatment. Analysis of scRNA-seq data from two independent patient cohorts revealed that HGSOC is driven by three core archetypal phenotypes, defined as oncogenic tasks that describe the majority of the transcriptome variation. A multi-task learning approach to identify the biological tasks of each archetype identified metabolism and proliferation, cellular defense response, and DNA repair signaling. The metabolism and proliferation archetype evolved during treatment and was enriched in cancer cells from patients that received multiple-lines of treatment and had elevated tumor burden indicated by CA-125 levels. The emergence of archetypes was not consistently associated with specific whole-genome driver mutations. However, archetypes were closely associated with subclonal populations at the single-cell level, indicating that subclones within a tumor often specialize in unique biological tasks. Our study reveals the core archetypes found in progressive HGSOC and shows consistent enrichment of subclones with the metabolism archetype as resistance is acquired to multiple lines of therapy. Citation Format: Aritro Nath, Patrick Cosgrove, Benjamin Copeland, Hoda Mirsafian, Elizabeth Christie, Lance Pflieger, Sumana Majumdar, Mihaela Cristea, Ernest Han, Stephen Lee, Edward Wang, Sian Fereday, Nadia Traficante, Ravi Salgia, Theresa Werner, Adam Cohen, Phillip Moos, Jeffrey Chang, David Bowtell, Andrea Bild. Evolution of core archetypal phenotypes in progressive high grade serous ovarian 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 3141.
Complexities in annotating surgical videos for building supervised deep learning models for critical steps of laparoscopic live donor nephrectomy
Authors: M. Bhandari, H. Ali, M. Desai, C. Mallikarjuna, A. Srivastava, D. Dubey, V. Tyagi, R. Ahlawat, C. Pratt, G.R. Choudhary, T. Trevor, M. Reddiboina
Journal: European Urology (2021)
Abstract 10878: Clusetered Myoblast Cell Injection Utilizing Cells Sheet Technology Augment Angiogenesis and Muscle Regeneration in a Mouse Model of Peripheral Artery Disease
Authors: Keisuke Miyake, Shigeru Miyagawa, Takashi Shibuya, Akima Harada, Shusaku Maeda, Takayoshi Ueno, Toru Kuratani, Koichi Toda, Yoshiki Sawa
Journal: Circulation (2019)

Introduction: In the current regenerative cell therapy in peripheral artery disease, the low survival rate of administered cells due to ischemic and inflammatory environment limits the efficacy of ...
非アルコール性脂肪肝炎(NASH)マウスモデルの異なる段階からの原発性肝組織培養の有効性【JST・京大機械翻訳】
Authors: Elbadawy Mohamed, Yamanaka Megumi, Goto Yuta, Hayashi Kimika, Tsunedomi Ryouichi, Hazama Shoichi, Nagano Hiroaki, Yoshida Toshinori, Shibutani Makoto, Ichikawa Ryo, Nakahara Junta, Omatsu Tsutomu, Mizutani Tetsuya, Katayama Yukie, Shinohara Yuta, Abugomaa Amira, Kaneda Masahiro, Yamawaki Hideyuki, Usui Tatsuya, Sasaki Kazuaki
Journal: Biomaterials (2020)
Abstract 1950: A ubiquitination cascade regulates the integrated stress response and epithelial cancer survival
Authors: Lisa D. Cervia, Tsukasa Shibue, Benjamin Gaeta, Ashir Borah, Lisa Leung, Naomi Li, Nancy Dumont, Alfredo Gonzalez, Nolan Bick, Mariya Kazachkova, Joshua Dempster, John M. Krill-Burger, Namrata Udeshi, Meagan Olive, Steven A. Carr, David E. Root, Federica Piccioni, James M. McFarland, Francisca Vazquez, William C. Hahn
Journal: Cancer Research (2021)

Abstract Systematic identification of signaling pathways required for the viability of cancer cells will facilitate the development of novel cancer therapies. We used gene essentiality measurements in 726 cancer cell lines to identify selective co-essentiality modules and found a functional ubiquitination cascade containing UBA6, BIRC6, KCMF1 and UBR4, which encode an E1, E2, and two heterodimeric E3 subunits, respectively, as a vulnerability in a subset of epithelial tumors. Suppressing BIRC6 in cancer cell lines that are dependent on this ubiquitination cascade led to a strong reduction in cell fitness in vitro, and to potent tumor regression and metastasis suppression in vivo. Mechanistically, BIRC6 suppression resulted in selective and robust activation of the integrated stress response (ISR) signaling via upregulation of the heme-regulated inhibitor (HRI). Using proteomic profiling, we found that HRI itself is a key degradation target of the UBA6/BIRC6/KCMF1/UBR4 cascade. These observations demonstrate a protein ubiquitination cascade regulating ISR and highlight the potential of this cascade as a novel therapeutic target for a subset of epithelial cancers. Citation Format: Lisa D. Cervia, Tsukasa Shibue, Benjamin Gaeta, Ashir Borah, Lisa Leung, Naomi Li, Nancy Dumont, Alfredo Gonzalez, Nolan Bick, Mariya Kazachkova, Joshua Dempster, John M. Krill-Burger, Namrata Udeshi, Meagan Olive, Steven A. Carr, David E. Root, Federica Piccioni, James M. McFarland, Francisca Vazquez, William C. Hahn. A ubiquitination cascade regulates the integrated stress response and epithelial 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 1950.