tbuckley/cabot-search huggingface dataset:
A Feedback Circuitry between Polycomb Signaling and Fructose-1, 6-Bisphosphatase Enables Hepatic and Renal Tumorigenesis
Authors: Kun Liao, Shuye Deng, Liyan Xu, Wenfeng Pan, Shiyu Yang, Fufu Zheng, Xingui Wu, Hongrong Hu, Zhijun Liu, Junhang Luo, Rui Zhang, Dong-Ming Kuang, Jiajun Dong, Yi Wu, Hui Zhang, Penghui Zhou, Jin-Xin Bei, Yang Xu, Yin Ji, Peng Wang, Huai-Qiang Ju, Rui-Hua Xu, Bo Li
Journal: Cancer Research (2020)

Suppression of gluconeogenesis elevates glycolysis and is commonly observed in tumors derived from gluconeogenic tissues including liver and kidney, yet the definitive regulatory mechanism remains elusive. Here, we screened an array of transcription regulators and identified the enhancer of zeste homolog 2 (EZH2) as a key factor that inhibits gluconeogenesis in cancer cells. Specifically, EZH2 repressed the expression of a rate-limiting gluconeogenic enzyme fructose-1, 6-bisphosphatase 1 (FBP1) and promoted tumor growth primarily through FBP1 suppression. Furthermore, EZH2 was upregulated by genotoxins that commonly induce hepatic and renal tumorigenesis. Genotoxin treatments augmented EZH2 acetylation, leading to reduced association between EZH2 and its E3 ubiquitin ligase SMURF2. Consequently, EZH2 became less ubiquitinated and more stabilized, promoting FBP1 attenuation and tumor formation. Intriguingly, FBP1 physically interacted with EZH2, competed for EZH2 binding, and dissembled the polycomb complex. Therefore, FBP1 suppresses polycomb-initiated transcriptional responses and constitutes a double-negative feedback loop indispensable for EZH2-promoted tumorigenesis. Finally, EZH2 and FBP1 levels were inversely correlated in tumor tissues and accurately predicted patient survival. This work reveals an unexpected cross-talk between epigenetic and metabolic events, and identifies a new feedback circuitry that highlights EZH2 inhibitors as liver and kidney cancer therapeutics. SIGNIFICANCE: A novel feedback loop involving EZH2 and suppression of the gluconeogenesis enzyme FBP1 promotes hepatocellular cancer growth.See related commentary by Leithner, p. 657.
Ambulatory Patients with Metastatic or Locally Advanced Cancer: is Body Mass Index ≥ 35 A Risk Factor for Thromboembolism also in European Countries?
Authors: S. Barni, R. Labianca, G. Gasparini, E. Bonizzoni, F. Petrelli, T. Perrone, M. Verso
Journal: Annals of Oncology (2012)
A Randomised Multicentre Trial of Epirubicin, Oxaliplatin and Capecitabine (EOC) + Panitumumab in advanced Oesophago-Gastric Cancer (REAL3): Updated Results
Authors: T.S. Waddell, J. Reis-Filho, D. Gonzalez-De-Castro, I. Chau, A. Wotherspoon, S. Gupta, C. Saffery, G. Middleton, J. Wadsley, D. Cunningham
Journal: Annals of Oncology (2012)
Acalabrutinib plus Obinutuzumab in Treatment-Naïve and Relapsed/Refractory Chronic Lymphocytic Leukemia
Authors: Jennifer A. Woyach, James S. Blachly, Kerry A. Rogers, Seema A. Bhat, Mojgan Jianfar, Gerard Lozanski, David M. Weiss, Barbara L. Andersen, Michael Gulrajani, Melanie M. Frigault, Ahmed Hamdy, Raquel Izumi, Veerendra Munugalavadla, Cheng Quah, Min-Hui Wang, John C. Byrd
Journal: Cancer Discovery (2020)

Acalabrutinib is a selective irreversible Bruton tyrosine kinase (BTK) inhibitor that does not affect IL2-associated tyrosine kinase or antibody-dependent cellular cytotoxicity, making it an attractive candidate for combination therapy with anti-CD20 antibodies. We investigated acalabrutinib plus obinutuzumab in a phase Ib/II study (NCT02296918) of patients with treatment-naïve or relapsed/refractory chronic lymphocytic leukemia (CLL). Nineteen treatment-naïve and 26 relapsed/refractory patients were treated with acalabrutinib (100 mg twice daily) until progression and obinutuzumab (cycle 1: 100 mg day 1, 900 mg day 2, 1000 mg days 8 and 15; cycles 2-6: 1,000 mg day 1). Grade 3/4 adverse events occurred in 71% of patients. Overall response rates were 95% (treatment-naïve) and 92% (relapsed/refractory). Thirty-two percent of treatment-naïve and 8% of relapsed/refractory patients achieved complete remission. At 36 months, 94% (treatment-naïve) and 88% (relapsed/refractory) were progression free. Acalabrutinib plus obinutuzumab was well tolerated, producing high and durable responses in treatment-naïve and relapsed/refractory CLL. SIGNIFICANCE: Rituximab plus the less selective BTK inhibitor ibrutinib has not shown benefit in CLL; however, the selective BTK inhibitor acalabrutinib plus the antibody-dependent cellular cytotoxicity-enhanced antibody obinutuzumab yielded durable responses that deepened over time in treatment-naïve and relapsed/refractory CLL, supporting the evaluation of this approach in larger, comparative studies in CLL.This article is highlighted in the In This Issue feature, p. 327.
Sex Differences in Blood Pressure Trajectories Over the Life Course
Authors: Hongwei Ji, Andy Kim, Joseph E. Ebinger, Teemu J. Niiranen, Brian L. Claggett, C. Noel Bairey Merz, Susan Cheng
Journal: JAMA Cardiology (2020)

<h3>Importance</h3> If we assume that women and men exhibit variations of the same fundamental vascular physiology, then conventional analyses of subclinical measures would suggest that women catch up to men by midlife in the extent of potentially important vascular disease. Alternatively, under the assumption that vascular physiology may fundamentally differ between women and men, a sex-specific analysis of existing data could offer new insights and augment our understanding of sex differences in cardiovascular diseases. <h3>Objective</h3> To evaluate whether longitudinal patterns of blood pressure (BP) elevation differ between women and men during the life course when considering baseline BP levels as the reference. <h3>Design, Setting, and Participants</h3> We conducted sex-specific analyses of longitudinal BP measures (144 599 observations) collected for a period of 43 years (1971 to 2014) in 4 community-based US cohort studies. The combined total included 32 833 participants (54% female) spanning ages 5 to 98 years. Data were analyzed between May 4, 2019, and August 5, 2019. <h3>Exposures</h3> Age and serially assessed longitudinal BP measures: systolic BP, diastolic BP, mean arterial pressure (MAP), and pulse pressure (PP). <h3>Main Outcomes and Measures</h3> Sex-specific change in each primary BP measure compared with baseline BP levels, derived from multilevel longitudinal models fitted over the age span, and new-onset cardiovascular disease events. <h3>Results</h3> Of the 32 833 participants, 17 733 were women (54%). Women compared with men exhibited a steeper increase in BP that began as early as in the third decade and continued through the life course (likelihood ratio test χ<sup>2</sup> = 531 for systolic BP; χ<sup>2</sup> = 123 for diastolic BP; χ<sup>2</sup> = 325 for MAP; and χ<sup>2</sup> = 572 for PP;<i>P</i>for all &lt;.001). After adjustment for multiple cardiovascular disease risk factors, these between-sex differences in all BP trajectories persisted (likelihood ratio test χ<sup>2</sup> = 314 for systolic BP; χ<sup>2</sup> = 31 for diastolic BP; χ<sup>2</sup> = 129 for MAP; and χ<sup>2</sup> = 485 for PP;<i>P</i>for all &lt;.001). <h3>Conclusions and Relevance</h3> In contrast with the notion that important vascular disease processes in women lag behind men by 10 to 20 years, sex-specific analyses indicate that BP measures actually progress more rapidly in women than in men, beginning early in life. This early-onset sexual dimorphism may set the stage for later-life cardiovascular diseases that tend to present differently, not simply later, in women compared with men.
C-MYC as a New Predictive Biomarker for Sunitinib in Metastatic Renal Clear Cell Carcinoma
Authors: P. Maroto, E. Esteban, E. Fernández-Parra, M.J. Méndez-Vidal, M. Domenech, L. León, B. Pérez-Valderrama, V. Calderero, J.L. Perez Gracia, F. Algaba
Journal: Annals of Oncology (2012)
A Randomized Phase III Study Evaluating the Continuation of Bevacizumab (BV) Beyond Progression in Metastatic Colorectal Cancer (MCRC) Patients (PTS) Who Received BV as Part of First-Line Treatment: Results of the Bebyp Trial by the Gruppo Oncologico Nord Ovest (GONO)
Authors: G. Masi, F. Loupakis, L. Salvatore, C. Cremolini, L. Fornaro, M. Schirripa, E. Fea, C. Granetto, L. Antonuzzo, E. Giommoni, G. Allegrini, S. Cupini, C. Boni, M. Banzi, S. Chiara, C. Sonaglio, C. Valsuani, A. Bonetti, L. Boni, A. Falcone
Journal: Annals of Oncology (2012)
Runx2 Deficiency in Osteoblasts Promotes Myeloma Progression by Altering the Bone Microenvironment at New Bone Sites
Authors: Xiaoxuan Xu, Chao Zhang, Timothy N. Trotter, Pramod S. Gowda, Yun Lu, Selvarangan Ponnazhagan, Amjad Javed, Juan Li, Yang Yang
Journal: Cancer Research (2020)

Multiple myeloma is a plasma cell malignancy that thrives in the bone marrow (BM), with frequent progression to new local and distant bone sites. Our previous studies demonstrated that multiple myeloma cells at primary sites secrete soluble factors and suppress osteoblastogenesis via the inhibition of Runt-related transcription factor 2 (Runx2) in pre- and immature osteoblasts (OB) in new bone sites, prior to the arrival of metastatic tumor cells. However, it is unknown whether OB-Runx2 suppression in new bone sites feeds back to promote multiple myeloma dissemination to and progression in these areas. Hence, we developed a syngeneic mouse model of multiple myeloma in which Runx2 is specifically deleted in the immature OBs of C57BL6/KaLwRij mice (OB-Runx2
Clinical, Molecular Profiles and Response to Neoadjuvant Chemotherapy in Patients with Locally Advanced Breast Cancer: An Indian Experience
Authors: D. Arya, B. Parikh, P.M. Shah, S.N. Shukla, K.M. Patel, A.S. Anand, S.S. Talati, S.A. Shah, A.A. Patel, B.B. Parekh
Journal: Annals of Oncology (2012)
P1.20 CDX2 VDR Polymorphism Impinges on the Response of Cultured Breast Cancer Cell Lines to Vitamin D
Authors: C. Pulito, I. Terrenato, A. Sacconi, F. Biagioni, M. Mottolese, G. Blandino, P. Muti, E. Falvo, S. Strano
Journal: Annals of Oncology (2012)
Pain and Bowel Function Evolution, in Cancer Patients Treated with Strong Opioids at the First Time that they Report Moderate-Severe Pain. C2 Study
Authors: I. López Calderero, L. Zugazabeitia Olabarria, M.Á. Nuñez Viejo, J.M. García Bueno, E. Blanco Campanario, J. Contreras Martínez, M. López Mata, J.L. Marti Ciriquian, D. Isla Casado, M. Provencio Pulla
Journal: Annals of Oncology (2012)
MIR-99A/LET7C/MIR-125B Signature to Predict Sensitivity to Anti-Egfr Monoclonal AntiBodies in Metastatic Colorectal Cancer (MCRC)
Authors: F. Cappuzzo, A. Sacconi, L. Landi, F. Biagioni, V. Ludovini, E. Sensi, J. Salvini, G. Fontanini, G. Blandino, L. Crinò
Journal: Annals of Oncology (2012)
Identification of the first cases of complete CD16A deficiency: Association with persistent EBV infection
Authors: A. Pérez-Portilla, M. Moraru, Alfonso Blázquez-Moreno, Philipp Kolb, María Bravo García-Morato, Thanmayi Ranganath, Gloria Esteso, Carla Gianelli, Rebeca Rodríguez-Pena, Roberto Lozano-Rodríguez, Juan Manuel Torres-Canizales, Catherine A. Blish, Mar Vales-Gomez, Hartmut Hengel, Carlos Vilches, Eduardo López-Granados, Hugh T. Reyburn
Journal: Journal of Allergy and Clinical Immunology (2020)
Rapid Photocrosslinking of Silk Hydrogels with High Cell Density and Enhanced Shape Fidelity
Authors: Xiaolin Cui, Bram G. Soliman, Cesar R. Alcala‐Orozco, Jun Li, Michelle A. M. Vis, Miguel Santos, Steven G. Wise, Riccardo Levato, Jos Malda, Tim B. F. Woodfield, Jelena Rnjak‐Kovacina, Khoon S. Lim
Journal: Advanced Healthcare Materials (2020)

Silk fibroin hydrogels crosslinked through di-tyrosine bonds are clear, elastomeric constructs with immense potential in regenerative medicine applications. In this study, demonstrated is a new visible light-mediated photoredox system for di-tyrosine bond formation in silk fibroin that overcomes major limitations of current conventional enzymatic-based crosslinking. This photomediated system rapidly crosslinks silk fibroin (<1 min), allowing encapsulation of cells at significantly higher cell densities (15 million cells mL-1 ) while retaining high cell viability (>80%). The photocrosslinked silk hydrogels present more stable mechanical properties which do not undergo spontaneous transition to stiff, β-sheet-rich networks typically seen for enzymatically crosslinked systems. These hydrogels also support long-term culture of human articular chondrocytes, with excellent cartilage tissue formation. This system also facilitates the first demonstration of biofabrication of silk fibroin constructs in the absence of chemical modification of the protein structure or rheological additives. Cell-laden constructs with complex, ordered, graduated architectures, and high resolution (40 µm) are fabricated using the photocrosslinking system, which cannot be achieved using the enzymatic crosslinking system. Taken together, this work demonstrates the immense potential of a new crosslinking approach for fabrication of elastomeric silk hydrogels with applications in biofabrication and tissue regeneration.
Prognostic Role of Kras Mutations Detected by High-Sensitivity Taqmelt PCR Assay in Metastatic Colorectal Cancer
Authors: J. Garcia Foncillas, S. Zazo, C. Carames, G. Serrano, A. Leon, A. Campos, J.I. Martin-Valades, C. Cañadas, T. Hernandez-Guerrero, F. Rojo
Journal: Annals of Oncology (2012)
Long-term outcomes in patients with decompensated alcohol-related liver disease, steatohepatitis and Maddrey's discriminant function &lt;32
Authors: Delphine Degré, Rudolf E. Stauber, Gaël Englebert, Francesca Sarocchi, Laurine Verset, Florian Rainer, Walter Spindelboeck, Hassane Njimi, Eric Trépo, Thierry Gustot, Carolin Lackner, Pierre Deltenre, Christophe Moreno
Journal: Journal of Hepatology (2020)
Which is Your Choice? Neoadjuvant Adriamycin and Doxetaxel (AD) Versus Adriamycin, Cyclophosphamide and Paclitaxel (AC-T) in Locally Advanced Breast Cancer
Authors: S.Y. Kang, J.-H. Choi, H.W. Lee, M. Ahn, K.S. Kim
Journal: Annals of Oncology (2012)
The Influence of Lung Microbiota on Lung Carcinogenesis, Immunity, and Immunotherapy
Authors: Ariel G. Ramírez-Labrada, Dolores Isla, Angel Artal, Maykel Arias, Antonio Rezusta, Julián Pardo, Eva M. Gálvez
Journal: Trends in cancer (2020)

Microbiota have emerged as key modulators of both the carcinogenic process and the immune response against cancer cells, and, thus, it seems to influence the efficacy of immunotherapy. While most studies have focused on analyzing the influence of gut microbiota, its composition substantially differs from that in the lung. Here, we describe how microbial life in the lungs is associated with host immune status in the lungs and, thus, how the identification of the microbial populations in the lower respiratory tract rather than in the gut might be key to understanding the lung carcinogenic process and to predict the efficacy of different treatments. Understanding the influence of lung microbiota on host immunity may identify new therapeutic targets and help to design new immunotherapy approaches to treat lung cancer.
Myosin II Reactivation and Cytoskeletal Remodeling as a Hallmark and a Vulnerability in Melanoma Therapy Resistance
Authors: Jose L. Orgaz, Eva Crosas-Molist, Amine Sadok, Anna Perdrix-Rosell, Oscar Maiques, Irene Rodriguez-Hernandez, Jo Monger, Silvia Mele, Mirella Georgouli, Victoria Bridgeman, Panagiotis Karagiannis, Rebecca Lee, Pahini Pandya, Lena Boehme, Fredrik Wallberg, Chris Tape, Sophia N. Karagiannis, Ilaria Malanchi, Victoria Sanz-Moreno
Journal: Cancer Cell (2020)

Despite substantial clinical benefit of targeted and immune checkpoint blockade-based therapies in melanoma, resistance inevitably develops. We show cytoskeletal remodeling and changes in expression and activity of ROCK-myosin II pathway during acquisition of resistance to MAPK inhibitors. MAPK regulates myosin II activity, but after initial therapy response, drug-resistant clones restore myosin II activity to increase survival. High ROCK-myosin II activity correlates with aggressiveness, identifying targeted therapy- and immunotherapy-resistant melanomas. Survival of resistant cells is myosin II dependent, regardless of the therapy. ROCK-myosin II ablation specifically kills resistant cells via intrinsic lethal reactive oxygen species and unresolved DNA damage and limits extrinsic myeloid and lymphoid immunosuppression. Efficacy of targeted therapies and immunotherapies can be improved by combination with ROCK inhibitors.
P-0158 Treatment Outcomes of Gemcitabine Versus Gemcitabine Plus Platinum for Biliary Tract Cancer: A Korean Cancer Study Group Retrospective Analysis
Authors: In Gyu Hwang, Joung-Soon Jang, Hong Suk Song, Lee Myung Ah, Eun Mi Nam, Joo Han Lim, Kyung Hee Lee, Kyu Taek Lee, Dae Young Zang
Journal: Annals of Oncology (2012)
A class of costimulatory CD28-bispecific antibodies that enhance the antitumor activity of CD3-bispecific antibodies
Authors: Dimitris Skokos, Janelle C. Waite, Lauric Haber, Alison Crawford, Aynur Hermann, Erica Ullman, Rabih Slim, Stephen Godin, Dharani Ajithdoss, Xuan Ye, Bei Wang, Qi Wu, Ilyssa Ramos, Arpita Pawashe, Lauren Canova, Kristin Vazzana, Priyanka Ram, Evan Herlihy, Hassan Ahmed, Erin Oswald, Jacquelynn Golubov, Patrick Poon, Lauren Havel, Danica Chiu, Miguel Lazo, Kathleen Provoncha, Kevin Yu, Julie Kim, Jacqueline J. Warsaw, Nicole Stokes Oristian, Chia-Jen Siao, Drew Dudgeon, Tammy Huang, Terra Potocky, Joel Martin, Douglas MacDonald, Adelekan Oyejide, Ashique Rafique, William Poueymirou, Jessica R. Kirshner, Eric Smith, William Olson, John Lin, Gavin Thurston, Matthew A. Sleeman, Andrew J. Murphy, George D. Yancopoulos
Journal: Science Translational Medicine (2020)

CD28 bispecific antibodies are well tolerated and enhance the antitumor efficacy of CD3 bispecifics as a potential off-the-shelf antibody therapy.
GWAS of 165,084 Japanese individuals identified nine loci associated with dietary habits
Authors: Nana Matoba, Masato Akiyama, Kazuyoshi Ishigaki, Masahiro Kanai, Atsushi Takahashi, Yukihide Momozawa, Shiro Ikegawa, Masashi Ikeda, Nakao Iwata, Makoto Hirata, Koichi Matsuda, Yoshinori Murakami, Michiaki Kubo, Yoichiro Kamatani, Yukinori Okada
Journal: Nature Human Behaviour (2020)
Pkm2 Expression May Predict Chemosensitivity to Cisplatin-Based Chemotherapy in Metastatic Non-Small Cell Lung Cancer (NSCLC)
Authors: C. Papadaki, M. Sfakianaki, E. Lagoudaki, G. Giagkas, E. Tsakalaki, M. Trypaki, S. Pontikakis, A. Koulouridi, V. Georgoulias, I. Souglakos
Journal: Annals of Oncology (2012)
Phase II Trial of Carboplatin and Pemetrexed as First-Line Chemotherapy for Non-Squamous Non-Small Cell Lung Cancer and Correlation Between the Efficacy/Toxicity and Genetic Polymorphisms Associated with Pemetrexed Metabolism: Hokkaido Lung Cancer Clinical Study Group Trial (HOT) 0902
Authors: Y. Fujita, H. Yokouchi, S. Fujiuchi, T. Harada, M. Harada, K. Takamura, S. Oizumi, H. Isobe, H. Akita, M. Nishimura
Journal: Annals of Oncology (2012)
骨肉腫:BCOR‐CCNB3遺伝子融合で定義される骨肉腫の新しいサブタイプ
Authors: Pierron Gaeelle, Reynaud Stephanie, Ballet Stelly, Delattre Olivier, Tirode Franck, Lucchesi Carlo, Cohen-Gogo Sarah, Perrin Virginie, Coindre Jean-Michel
Journal: Nature Genetics (2012)
KBP-2010-CPHG: Characteristics of 6,083 New Cases of Nsclc According to Sex
Authors: D. Debieuvre, C. Locher, I. Bourlaud, M. Zaegel, M. Le Poulain-Doubliez, J. Piquet, T. Collon, F. Martin, F. Blanchon, M. Grivaux
Journal: Annals of Oncology (2012)
Increased Number of IL-17 Producing CD4+ T Cells in Low Risk Myelodysplastic Syndrome (MDS)
Authors: Shahram Y Kordasti, Behdad Afzali, Ziyi Lim, Wendy Ingram, Janet Hayden, Linda Barber, Giovanna Lombardi, Farzin Farzaneh, Ghulam J Mufti
Journal: Blood (2008)
Response to: Correspondence on “Immune checkpoint inhibitor-induced inflammatory arthritis persists after immunotherapy cessation” by Braaten <i>et al</i>
Authors: Laura C Cappelli, Clifton O Bingham, Tawnie Braaten, Ami A Shah
Journal: Annals of the Rheumatic Diseases (2020)

Response to: Correspondence on "Immune checkpoint inhibitor-induced inflammatory arthritis persists after immunotherapy cessation" by Braaten et alWe were interested to read the letter by Ceccarelli et al regarding their experience with Immune checkpoint inhibitor (ICI)-induced inflammatory arthritis (IA) at Sapienza University. 1 Their findings support that ICI-induced IA is a heterogeneous disease with differing outcomes.The differences in the cohorts studied may also give us insight into the risk factors for persistence in ICI-induced IA.The authors point out one main difference between the cohorts, type of ICI therapy.Indeed, combination anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)/anti-programmed cell death protein-1 (PD-1) therapy was an independent risk factor for persistent IA in our cohort, 2 and their study included only patients on anti-PD-1 agents.There are several other relevant differences.First, the patients had a shorter duration of ICI use before IA was diagnosed and corticosteroids were started as compared with our study.Duration of ICI therapy was also an independent risk factor for IA persistence in our cohort. 2Second, all patients in the study were evaluated deliberately for IA which likely led to earlier diagnosis and potentially milder disease.Disease activity is not specifically reported, but the higher incidence of IA (9.7%) than in any previously published studies suggests that milder disease was included. 1The need for multicentre, international efforts to characterise longitudinal outcomes for ICI-induced IA is apparent.