tbuckley/cabot-search huggingface dataset:
P-0297 Predictive/Prognostic Value of TS, KI-67, Egfr, MLH-1, MSH-2 and Trg in Locally Advanced Rectal Cancer Treated with Neoadjuvant Chemoradiation (Bmg-B1-Study)
Authors: Sara Pini, Claudio Ceccarelli, Francesca Di Fabio, Bruno Iacopino, Ferdinando Lecce, Giampaolo Ugolini, Francesco Varrese, Lorena Rojas Llimpe, Martoni Andera, Pinto Carmine
Journal: Annals of Oncology (2012)
Snake Recombination Landscapes Are Concentrated in Functional Regions despite PRDM9
Authors: Drew R Schield, Giulia I M Pasquesi, Blair W Perry, Richard H Adams, Zachary L Nikolakis, Aundrea K Westfall, Richard W Orton, Jesse M Meik, Stephen P Mackessy, Todd A Castoe
Journal: Molecular Biology and Evolution (2020)

Meiotic recombination in vertebrates is concentrated in hotspots throughout the genome. The location and stability of hotspots have been linked to the presence or absence of PRDM9, leading to two primary models for hotspot evolution derived from mammals and birds. Species with PRDM9-directed recombination have rapid turnover of hotspots concentrated in intergenic regions (i.e., mammals), whereas hotspots in species lacking PRDM9 are concentrated in functional regions and have greater stability over time (i.e., birds). Snakes possess PRDM9, yet virtually nothing is known about snake recombination. Here, we examine the recombination landscape and test hypotheses about the roles of PRDM9 in rattlesnakes. We find substantial variation in recombination rate within and among snake chromosomes, and positive correlations between recombination rate and gene density, GC content, and genetic diversity. Like mammals, snakes appear to have a functional and active PRDM9, but rather than being directed away from genes, snake hotspots are concentrated in promoters and functional regions-a pattern previously associated only with species that lack a functional PRDM9. Snakes therefore provide a unique example of recombination landscapes in which PRDM9 is functional, yet recombination hotspots are associated with functional genic regions-a combination of features that defy existing paradigms for recombination landscapes in vertebrates. Our findings also provide evidence that high recombination rates are a shared feature of vertebrate microchromosomes. Our results challenge previous assumptions about the adaptive role of PRDM9 and highlight the diversity of recombination landscape features among vertebrate lineages.
Usefulness of Serial Measurement of Serum N-Telopeptides of Type I Collogen (NTX) in Patients with Lung Cancer who Developed Bone Metastasis: A Prospective Study
Authors: M. Tamiya, H. Okada, M. Kobayashi, N. Okamoto, H. Suzuki, N. Morishita, Y. Matsuura, H. Daga, S. Tokunaga, K. Taira, M. Hattori, N. Miyamoto, S. Sasada, K. Takeda, T. Hirashima
Journal: Annals of Oncology (2012)
For Which pT1A, bN0M0 Hormone Responsive Invasive Breast Carcinomas Could Endocrine Therapy be Avoided?
Authors: C. Perrin, J. Edeline, J. Leseur, V. Lavoué, P. Tas, H. Mesbah, C. Lefeuvre-Plesse, D. Gedouin, F. Penault-Llorca, P. Kerbrat
Journal: Annals of Oncology (2012)
Roles of cMET/ErbB3 activation and overexpression in the development of resistance to EGFR inhibitors in NSCLC patients.
Authors: Myung-Ju Ahn, Silvia Park, Jong-Mu Sun, Jin Seok Ahn, Keunchil Park, Emma J. Langley, Phillip Sangwook Kim, Sharat Singh, Steve Lockton
Journal: Journal of Clinical Oncology (2013)

11113 Background: Multifaceted efforts in the molecular and cellular research of lung cancer revealed many critical pathway dysregulations due genetic and epigenetic alterations to alter balances in signal transduction leading to carcinogenesis. Methods: US guided FNAs or pleural fluid were collected from 44 NSCLC patients enrolled in on-going prospective study involving EGFR inhibitors (gefitinib, erlotinib, or afatinib) and evaluated for EGFR as well as other various receptor tyrosine kinases (RTKs, i.e. ErbB2, ErbB3, cMET, IGF1R, ALK, etc) and downstream AKT and MAPK pathway proteins for their level of expression and activation in order to 1) Compare objective response rate according to the expression/activation of RTK and pathway proteins; 2) Evaluate the modulation of the RTK and pathway proteins during the treatment of EGFRi; 3) Correlate between activating EGFR gene mutations and RTK activation in patients treated with EGFRi. Results: Majority of patients over-expressed EGFR. While not overexpressed, varying and significant levels of cMET and ErbB3 were found and quantitated in each patient. A striking difference in PFS was observed with respect to relative levels of cMET to EGFR in pretreatment FNA. Regardless of EGFR mutation status, patients with higher levels of EGFR to cMET (or higher E/M-Index) showed superior PFS. With an increase in cMET involvement (or decrease in E/M-Index; continuous variable), NSCLC patients exhibited worse clinical outcome with reduction in PFS (as shown in the Table). Furthermore, patients with shorter PFS (&lt; 8 months) had significantly higher levels of total and phosphorylated ErbB3 (67% positive) than patients with longer PFS (&gt;8 months, 27% positive). Conclusions: This study clearly demonstrates the critical roles of cMET and ErbB3 in resistance to EGFR inhibitors in NSCLC patients. E/M-Index and activation may serve as predictive markers for treatment selection with EGFRi and cMETi, and should be validated in prospective clinical studies. [Table: see text]
Safety Data of Cabazitaxel (JEVTANA®) in Patients Treated for Metastatic Castration Resistant Prostate Cancer after Docetaxel Treatment: Results of a Cohort of Patients During the Temporary Authorization for Use in France (ATU)
Authors: N. Houede, J. Eymard, T. Zoubir
Journal: Annals of Oncology (2012)
P-0182 A Common Gene Variant in PLS3 Predicts Colon Cancer Recurrence in Women
Authors: Joanna Szkandera, Thomas Winder, Gudrun Absenger, Michael Stotz, Melanie Weissmüller, Tanja Langsenlehner, Guenter Hofmann, Hellmut Samonigg, Wilfried Renner, Armin Gerger
Journal: Annals of Oncology (2012)
Activation of Canonical BMP4-SMAD7 Signaling Suppresses Breast Cancer Metastasis
Authors: Bedrich L. Eckhardt, Yuan Cao, Andrew D. Redfern, Lap Hing Chi, Allan D. Burrows, Suraya Roslan, Erica K. Sloan, Belinda S. Parker, Sherene Loi, Naoto T. Ueno, Peter K. H. Lau, Bruce Latham, Robin L. Anderson
Journal: Cancer Research (2020)

Metastasis is the major cause of death in patients with cancer; with no therapeutic cure, treatments remain largely palliative. As such, new targets and therapeutic strategies are urgently required. Here, we show that bone morphogenetic protein-4 (BMP4) blocks metastasis in animal models of breast cancer and predicts improved survival in patients. In preclinical models of spontaneous metastasis, BMP4 acted as an autocrine mediator to modulate a range of known metastasis-regulating genes, including Smad7, via activation of canonical BMP-SMAD signaling. Restored BMP4 expression or therapeutically administered BMP4 protein, blocked metastasis and increased survival by sensitizing cancer cells to anoikis, thereby reducing the number of circulating tumor cells. Gene silencing of Bmp4 or its downstream mediator Smad7, reversed this phenotype. Administration of recombinant BMP4 markedly reduced spontaneous metastasis to lung and bone. Elevated levels of BMP4 and SMAD7 were prognostic for improved recurrence-free survival and overall survival in patients with breast cancer, indicating the importance of canonical BMP4 signaling in the suppression of metastasis and highlighting new avenues for therapy against metastatic disease. SIGNIFICANCE: Targeting the BMP4-SMAD7 signaling axis presents a novel therapeutic strategy to combat metastatic breast cancer, a disease that has had no reduction in patient mortality over 20 years. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/6/1304/F1.large.jpg.
A changed life: the life experiences of patients with psoriasis receiving biological treatment
Authors: B. Trettin, S.R. Feldman, F. Andersen, D.B. Danbjørg, H. Agerskov
Journal: British Journal of Dermatology (2020)

Psoriasis has a large negative impact on quality of life and is associated with both depression and anxiety. The introduction of biologics has improved treatment outcomes, but the ways in which patients perceive these improvements are not well characterized.To investigate the everyday life experiences of patients with psoriasis receiving biological treatment in order to gain an understanding of their needs and to improve the quality of care.A qualitative narrative methodology was utilized. In total 48 h of participant observations during consultations, and 15 semistructured interviews, were conducted with patients receiving biological treatment. Data were analysed according to Ricoeur's theory of interpretation.Receiving biological treatment was experienced as a turning point, with a significant impact on physical, psychological and emotional levels. However, psychological consequences, such as isolation and social withdrawal, seemed to be a part of the patient's identity; the negative perceptions of psoriasis left marks behind that affected the patient's self-image. Perceived fear of discontinuation of the biological treatment resulted in insecurity, and patients were reluctant to initiate discussion about these concerns with healthcare professionals.Providing assistance when patients enter the transition of receiving biological treatment may be important. Patients' fear of biological treatment being discontinued is an ongoing issue that healthcare professionals could address.
A First-In-Human Dose-Finding Study of the Alk/Egfr Inhibitor AP26113 in Patients with Advanced Malignancies
Authors: S. Gettinger, G.J. Weiss, R. Salgia, L. Bazhenova, N.I. Narasimhan, D.J. Dorer, V.M. Rivera, J. Zhang, T. Clackson, F. Haluska, A.T. Shaw, D.R. Camidge
Journal: Annals of Oncology (2012)
Phase 3 Correct Trial of Regorafenib in Metastatic Colorectal Cancer (MCRC): Overall Survival Update
Authors: E.J.D. Van Cutsem, A. Grothey, A. Sobrero, S. Siena, A. Falcone, M. Ychou, Y. Humblet, O. Bouche, L. Mineur, C. Barone, A. Adenis, J. Tabernero, T. Yoshino, H.-J. Lenz, R. Goldberg, D.J. Sargent, F. Cihon, L. Cupit, A. Wagner, D. Laurent
Journal: Annals of Oncology (2012)
A Phase I, Dose-Escalation Study of Mgcd265, A Multi-Targeted Oral Tyrosine Kinase Receptor Inhibitor, for Treatment of Advanced Solid Tumors
Authors: H.I. Hurwitz, C.K. Kollmannsberger, M. Juretic, J. Wang, M. Fournel, C. Bonfils, C. Maroun, R.W. Humphrey, J. Besterman, G. Shapiro
Journal: Annals of Oncology (2012)
Immunogenicity of Trastuzumab Intravenous and Subcutaneous Formulations in the Phase III Hannah Study
Authors: R. Hegg, T. Pienkowski, S. Chen, E. Staroslawska, S. Falcon, N. Kovalenko, N. Al-Sakaff, D. Heinzmann, G. Kolaitis, G. Ismael
Journal: Annals of Oncology (2012)
Abstract 9554: Differences Between Women’s And Men’s Patterns of Revisits in a Cardiac Emergency Department
Authors: Sylvie Cossette, Marc-André Maheu-Cadotte, Tanya Mailhot, Patrick Lavoie, Guillaume Fontaine, Alexis Cournoyer, Alain Vadeboncoeur
Journal: Circulation (2019)

Introduction: Patterns of ED revisits in cardiology-specialized hospitals have rarely been reported because of their specificity. Moreover, women and men are known to differ on illness characterist...
An Open-Circuit Helium Method for Measuring Functional Residual Capacity and Defective Intrapulmonary Gas Mixing1
Authors: J. B. Hickam, E. Blair, R. Frayser
Journal: Journal of Clinical Investigation (1954)

In pulmonary disease the inspired air is often distributed unequally throughout the lung. The volume of the poorly aerated regions of the lung and their rate of ventilation are of importance to the clinician but quantitation of these values has been difficult.  The situation was much clarified in 1950 by Robertson, Siri, and Jones (1) who demonstrated that an unequally ventilated lung behaves as though it consisted of a number of subdivisions of smaller size, each of which is homogeneously ventilated at its own particular rate. Preliminary work which led to the same concept was also reported at this time by Fowler, Cornish, and Kety (2). By continuously following the course of nitrogen elimination from the lungs of a subject breathing oxygen, it was possible to characterize these lung subdivisions in terms of size and ventilation rate. This information describes an unequally ventilated lung in a way which permits useful,
Curcuma Longa Extract is Effective in Improving Inflammatory Status and Redox Balance in Patients with Cancer-Related Cachexia and Oxidative Stress
Authors: G. Mantovani, C. Madeddu, F. Panzone, M.C. Cau, G. Antoni, F. Leo, A. Maccio', R. Serpe
Journal: Annals of Oncology (2012)
Non-thermal histotripsy tumor ablation promotes abscopal immune responses that enhance cancer immunotherapy
Authors: Shibin Qu, Tejaswi Worlikar, Amy E Felsted, Anutosh Ganguly, Megan V Beems, Ryan Hubbard, Ashley L Pepple, Alicia A Kevelin, Hannah Garavaglia, Joe Dib, Mariam Toma, Hai Huang, Allan Tsung, Zhen Xu, Clifford Suhyun Cho
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Developing the ability to use tumor-directed therapies to trigger potentially therapeutic immune responses against cancer antigens remains a high priority for cancer immunotherapy. We hypothesized that histotripsy, a novel non-invasive, non-thermal ablation modality that uses ultrasound-generated acoustic cavitation to disrupt tissues, could engender adaptive immune responses to tumor antigens. Methods Immunocompetent C57BL/6 mice inoculated with flank melanoma or hepatocellular carcinoma tumors were treated with histotripsy, thermal ablation, radiation therapy, or cytotoxic T lymphocyte-associated protein-4 (CTLA-4) blockade checkpoint inhibition. Lymphocyte responses were measured using flow cytometric and immunohistochemical analyses. The impact of histotripsy on abscopal immune responses was assessed in mice bearing bilateral tumors, or unilateral tumors with pulmonary tumors established via tail vein injection. Results Histotripsy ablation of subcutaneous murine melanoma tumors stimulated potent local intratumoral infiltration of innate and adaptive immune cell populations. The magnitude of this immunostimulation was stronger than that seen with tumor irradiation or thermal ablation. Histotripsy also promoted abscopal immune responses at untreated tumor sites and inhibited growth of pulmonary metastases. Histotripsy was capable of releasing tumor antigens with retained immunogenicity, and this immunostimulatory effect was associated with calreticulin translocation to the cellular membrane and local and systemic release of high mobility group box protein 1. Histotripsy ablation potentiated the efficacy of checkpoint inhibition immunotherapy in murine models of melanoma and hepatocellular carcinoma. Conclusions These preclinical observations suggest that non-invasive histotripsy ablation can be used to stimulate tumor-specific immune responses capable of magnifying the impact of checkpoint inhibition immunotherapy.
Nucleophosmin mutations confer an independent favorable prognostic impact in 869 pediatric patients with acute myeloid leukemia
Authors: Lu-Hong Xu, Jian-Pei Fang, Yao-Chung Liu, Adrianna I. Jones, Li Chai
Journal: Blood Cancer Journal (2020)

Abstract Studies on the clinical significance of Nucleophosmin (NPM1) mutations in pediatric AML in a large cohort are lacking. Moreover, the prognosis of patients with co-occurring NPM1 and FLT3/ITD mutations is controversial. Here, we analyzed the impact of NPM1 mutations on prognoses of 869 pediatric AML patients from the TAGET dataset. The frequency of NPM1 mutations was 7.6%. NPM1 mutations were significantly associated with older age ( P &lt; 0.001), normal cytogenetics ( P &lt; 0.001), FLT3/ITD mutations ( P &lt; 0.001), and high complete remission induction rates ( P &lt; 0.05). Overall, NPM1-mutated patients had a significantly better 5-year EFS ( P = 0.001) and OS ( P = 0.016) compared to NPM1 wild-type patients, and this favorable impact was maintained even in the presence of FLT3/ITD mutations. Stem cell transplantation had no significant effect on the survival of patients with both NPM1 and FLT3/ITD mutations. Multivariate analysis revealed that NPM1 mutations were independent predictors of better outcome in terms of EFS ( P = 0.004) and OS ( P = 0.012). Our findings showed that NPM1 mutations confer an independent favorable prognostic impact in pediatric AML despite of FLT3/ITD mutations. In addition, pediatric AML patients with both NPM1 and FLT3/ITD mutations appear to have favorable prognoses and may not need hematopoietic stem cell transplantations.
Second-Line Docetaxel (D) in Metastatic Gastric Cancer (MGC)
Authors: C. Caparello, M. Lencioni, E. Vasile, S. Caponi, S. Santi, M.G. Fabrini, L. Ginocchi, M. Lucchesi, S. Ricci, A. Falcone
Journal: Annals of Oncology (2012)
Tumor Analyses Reveal Squamous Transformation and Off-Target Alterations As Early Resistance Mechanisms to First-line Osimertinib in<i>EGFR</i>-Mutant Lung Cancer
Authors: Adam J. Schoenfeld, Joseph M. Chan, Daisuke Kubota, Hiroki Sato, Hira Rizvi, Yahya Daneshbod, Jason C. Chang, Paul K. Paik, Michael Offin, Maria E. Arcila, Monika A. Davare, Ujwal Shinde, Dana Pe'er, Natasha Rekhtman, Mark G. Kris, Romel Somwar, Gregory J. Riely, Marc Ladanyi, Helena A. Yu
Journal: Clinical Cancer Research (2020)

Patterns of resistance to first-line osimertinib are not well-established and have primarily been evaluated using plasma assays, which cannot detect histologic transformation and have differential sensitivity for copy number changes and chromosomal rearrangements.
Response Evaluation Using Recist and Choi Criteria in Patients with Well-Differentiated Pancreatic Neuroendocrine Tumors (PNET) Treated with Sunitinib or Everolimus
Authors: C. Dreyer, O. Hentic, M. Zappa, P. Hammel, M. Bouattour, C. Mateescu, S. Faivre, P. Ruszniewski, E. Raymond
Journal: Annals of Oncology (2012)
The Efficacy and Safety of Bevacizumab Beyond First Progression in Japanese Patients Treated with First-Line Mfolfox6 Followed By Second-Line Folfiri in Advanced Colorectal Cancer: a Multicenter, Single-Arm Phase Ii Trial (CCOG-0801); Final Report
Authors: G. Nakayama, K. Ishigure, A. Ishiyama, K. Uehara, T. Fujii, N. Hayashi, Y. Ando, Y. Kodera
Journal: Annals of Oncology (2012)
Mendelian randomisation supports causal link between obesity and asthma
Authors: Diana A van der Plaat
Journal: Thorax (2020)

Over the last few decades the prevalence of both obesity and asthma has increased substantially in many parts of the world. A clear link between obesity and asthma incidence and severity has been shown in both children and adults in observational studies.1 2 The biological mechanisms underlying this relationship are not fully understood. Hypotheses to explain the association include mechanisms related to one or more factors, including systemic inflammation, endocrine factors, oxidative stress, decreased lung volumes and comorbidities (type 2 diabetes, obstructive sleep apnoea and gastro-oesophageal reflux disease).3–6 The systemic inflammation pathway has gained particular traction, as both obese subjects and asthmatics have high inflammatory burdens. In addition, obese patients with asthma present with a different type of airway inflammation, tending to be more neutrophilic than eosinophilic.3 Controversy exists over whether obesity has a different effect on asthma in males and females, as studies in children show mixed results while some studies in adults suggest stronger effects in females.4 5 Furthermore, there has been a concern that the body mass index (BMI)–asthma association is due to reverse causation; that is, that people with asthma become obese due to the impact of asthma on their ability to remain active or perhaps even due to medications. Overall, findings by observational studies are susceptible to bias (confounding) and cannot elucidate the directionality of the relationship between obesity and asthma.

The Mendelian randomisation (MR) approach is increasingly used to assess causal relationships and can be regarded as a ‘natural’ randomised controlled trial. MR uses genetic variants (single nucleotide polymorphisms; SNP), which were randomly assigned at conception, as proxies (‘instrumental variables’) for an exposure of interest.7 Indirect evidence of a causal effect of the exposure on the outcome is provided when the SNPs that are known to modify the exposure …
P-0258 High Dose Irinotecan Associated with LV5FU2 and Cetuximab in First Line in Colorectal Metastatic Cancer (Erbifort): Multicentric Phase II Study
Authors: Jean Marc Phelip, Laurent Mineur, Christellela De Fouchardière, Denis Pezet, Françoise Desseigne, Jean Louis Jouve, Christine Rebischung, Xavier Roblin, Jean Gabriel Balique, Jean Louis Quesada, Serban Bageacu, Christophe Mendoza, Claire Garnier, Etienne Chatelut, Michel Rivoire
Journal: Annals of Oncology (2012)
Efficacy and Safety of Bevacizumab Combined with Chemotherapy in Daily Practice in 765 French Patients with MCRC: The Concert Cohort at a Maximum of 24 Months Follow-Up
Authors: J. Bennouna, M. Ducreux, B. Asselain, J. Phelip, T. André, H. Senellart, B. Commenges
Journal: Annals of Oncology (2012)
PD-0013 Methylation Based Biomarkers for Non-Invasive Early Detection of Colorectal Cancer
Authors: Deeqa Ahmed, Trude Ågesen, Stine Danielsen, Michael Bretthauer, Espen Thiis-Evensen, Geir Hoff, Torleiv Rognum, Arild Nesbakken, Ragnhild Lothe, Guro Lind
Journal: Annals of Oncology (2012)
P1.05 Upfront Genomic Testing for Patients With Non-Small Cell Lung Cancer Receiving First-Line Platinum-Based Regimen: Preliminary Result of the Msn Study
Authors: D. Planchard, B. Lueza, A. Rahal, L. Lacroix, M. Ngocamus, N. Auger, P. Saulnier, P. Dorfmuller, T. Le Chevalier, A. Celebic, J.P. Pignon, J.C. Soria, B. Besse
Journal: Annals of Oncology (2012)
Gene Amplification of ACTN4 in Lung Cancer: A Novel Prognostic Indicator for Stage I Adenocarcinoma of The Lung
Authors: K. Honda, R. Noro, N. Miura, K. Tsuta, G. Ishii, H. Tsuda, A. Gennma, H. Asamura, K. Nagai, T. Yamada
Journal: Annals of Oncology (2012)