tbuckley/cabot-search huggingface dataset:
Cabozantinib (XL184) At 40 Mg in Patients with Metastatic Castration Resistant Prostate Cancer (MCRPC): Results of a Phase 2 Non-Randomized Expansion Cohort (NRE)
Authors: J.S. de Bono, M.R. Smith, D. Rathkopf, P.G. Corn, D. Mukherji, A.L. Harzstark, O.A. Sartor, D.C. Smith, N. Tunariu, C. Sweeney
Journal: Annals of Oncology (2012)
Pazopanib, a Novel Multi-Targeted Kinase Inhibitor, Shows Potent in vitro Antitumor Activity in Gastric Cancer Cell Lines with FGFR2 Amplification
Authors: J.O. Park, H.-L. Jang, J. Lee, Y.-L. Choi, K.-M. Kim, J. Cho, S.H. Park, Y.S. Park, H.Y. Lim, M. Yashiro, W.K. Kang
Journal: Annals of Oncology (2012)
Randomized, Open-Label, Phase III Trial Of Pazopanib Versus Sunitinib In First-Line Treatment Of Patients With Metastatic Renal Cell Carcinoma (MRCC): Results of the Comparz Trial
Authors: R. Motzer, T.E. Hutson, J. Reeves, R. Hawkins, J. Guo, P. Nathan, M. Staehler, P. de Souza, J.R. Merchan, K. Fife, J. Jin, R. Jones, H. Uemura, U. De Giorgi, U. Harmenberg, J. Wang, D. Cella, L. McCann, K. Deen, T.K. Choueiri
Journal: Annals of Oncology (2012)
A Randomized Phase II Trial Comparing Standard Pain Control with or Without Gabapentin for the Treatment of Pain Related to Radiation-Induced Mucositis in Head and Neck Cancer
Authors: T. Kataoka, N. Kiyota, T. Shimada, M. Toyoda, Y. Fujiwara, K. Nibu, T. Komori, R. Sasaki, T. Mukohara, H. Minami
Journal: Annals of Oncology (2012)
Incidence of Infectious Complications Following Cochlear Implantation in Children and Adults
Authors: Daniel P. Lander, Nedim Durakovic, Dorina Kallogjeri, Pawina Jiramongkolchai, Margaret A. Olsen, Jay F. Piccirillo, Craig A. Buchman
Journal: JAMA (2020)

This cohort study uses data from state health care databases to determine the incidence and timing of infectious complications following cochlear implant surgery among patients in 5 US states between 2006 and 2016.
P-0061 Docetaxel Monotherapy as a Second-Line Salvage Treatment in Advanced Gastric Cancer: Experience of 40 Patients with Prognostic Factor Analysis
Authors: Elisenda Llabrés, Martín Francisco Javier Pérez, Mariona Calvo, Berta Laquente, Silvia Vázquez, Maica Galán
Journal: Annals of Oncology (2012)
Everolimus in Patients with Metastatic Renal Cell Carcinoma Who Progress after Initial Vascular Endothelial Growth Factor Receptor-Tyrosine Kinase Inhibitor (VEGFR-TKI) Therapy: UK Results from the react Trial on Behalf of the UK React Investigators
Authors: S. Chowdhury, J. Larkin
Journal: Annals of Oncology (2012)
Reduced Translational Efficiency of Eukaryotic Genes after Duplication Events
Authors: Andrew Ying-Fei Chang, Ben-Yang Liao
Journal: Molecular Biology and Evolution (2019)

Control of gene expression has been found to be predominantly determined at the level of protein translation. However, to date, reduced expression from duplicated genes in eukaryotes for dosage maintenance has only been linked to transcriptional control involving epigenetic mechanisms. Here, we hypothesize that dosage maintenance following gene duplication also involves regulation at the protein level. To test this hypothesis, we compared transcriptome and proteome data of yeast models, Saccharomyces cerevisiae and Schizosaccharomyces pombe, and worm models, Caenorhabditis elegans and Caenorhabditis briggsae, to investigate lineage-specifically duplicated genes. Duplicated genes in both eukaryotic models exhibited a reduced protein-to-mRNA abundance ratio. Moreover, dosage sensitive genes, represented by genes encoding protein complex subunits, reduced their protein-to-mRNA abundance ratios more significantly than the other genes after duplication events. An analysis of ribosome profiling (Ribo-Seq) data further showed that reduced translational efficiency was more prominent for dosage sensitive genes than for the other genes. Meanwhile, no difference in protein degradation rate was associated with duplication events. Translationally repressed duplicated genes were also more likely to be inhibited at the level of transcription. Taken together, these results suggest that translation-mediated dosage control is partially contributed by natural selection and it enhances transcriptional control in maintaining gene dosage after gene duplication events during eukaryotic genome evolution.
Might Early Metabolic Response by 18F-FDG-PET/CT be Useful to Select Patients (PTS) With Breast Cancer (BC) who Will not Optimally Respond to Preoperative Chemotherapy (PCT)?
Authors: G. Zucchini, S. Quercia, C. Zamagni, D. Santini, M. Taffurelli, S. Fanti, A.A. Martoni
Journal: Annals of Oncology (2012)
O-0022 X-Pect Study Results: A Phase III Randomized Study of Perifosine Plus Capecitabine vs. Placebo Plus Capecitabine in Refractory mCRC Patients
Authors: Johanna Bendell, Thomas Ervin, Neil Senzer, Donald Richards, Irfan Firdaus, A. Craig Lockhart, Allen Cohn, Mansoor Saleh, Peter Sportelli, Lesa Gardner, Cathy Eng
Journal: Annals of Oncology (2012)
The sensitivity and specifity of DR-70 as a tumor marker for gastrointestinal cancers.
Authors: Burcak Erkol, Basak Bala Oven, Vedat Bayoglu, Nurcan Paker, Koray Kochan, Selvinaz Ozkara, Metin Tilki, Ali Surmelioglu, Atakan Yesil, Can Gonen
Journal: Journal of Clinical Oncology (2013)

e22061 Background: There is a great need to detect gastrointestinal cancers at an early stage, reduce morbidity and mortality. CEA and CA 19-9 are widely used serological markers for gastrointestinal cancers during follow-up. Their utility are limited because of their low sensitivity. In this study, a novel tumor marker DR-70 is evaluated for the sensitivity and specificity, relationship between clinical parameters and compared with CEA and CA 19-9. Methods: Blood sera of 101 histologically proven gastrointestinal cancer patients (38 female, 63 male; 42 colon, 25 rectum, 18 stomach, 9 pancreas, 4 esophagus and 3 cholangiocellular carcinomas) and 105 healthy blood donors were included. The TNM stage of the disease and histologic grade was shown. All patients and controls were also tested for CEA and CA 19-9 levels. In DR-70 immunoassay, the fibrin degradation products were quantitatively measured using ELISA DR-70 kits. Results: The median DR-70, CEA and CA19-9 levels were 1.6 µg/mL, 3.05 ng/mL and 22.2 IU/L in cancer patients, they were lower in healthy control 0.5 µg/mL, 0.9 ng/mL, 1.9 IU/L; p &lt; 0.001. While the stage and grade increased, the levels of DR-70, CEA and CA-19-9 (p &lt; 0.05) were increased significantly. DR-70 and CA19-9 values were highest in patients with pancreas, and lowest in rectum cancer, there was no statistically significant difference between tumor localization and CEA levels.The sensitivity, specificity and the cut-off value of DR-70, in patients with malignancy by using ROC analysis were found as 97%, 95% and &lt; 0.75 µg/mL, respectively. The positive and negative predictive values were 95%, and 97% and the efficacy was 96%. Sensitivities of CEA (cut off value 3ng/mL) and CA 19-9 (cut off value 37 U/ml) were 52% and 39% respectively, the specificities were 94% and 99% for CEA and CA 19-9, respectively; sensitivity increased by combined use of both of them. Conclusions: Due to its high sensitivity and specificity, high positive and negative predictive values DR-70 can be used more frequently as a tumor marker for detection of gastrointestinal cancer. It can also be used in tumor progression and treatment follow-up because of positive correlation between DR-70 levels and the tumor stage.
Supporting clinical decision making in advanced melanoma by preclinical testing in personalized immune-humanized xenograft mouse models
Authors: L. Ny, L.Y. Rizzo, V. Belgrano, J. Karlsson, H. Jespersen, L. Carstam, R.O. Bagge, L.M. Nilsson, J.A. Nilsson
Journal: Annals of Oncology (2020)

The mouse strains usually used to generate patient-derived xenografts (PDXs) are immunocompromised, rendering them unsuitable for immunotherapy studies. Here we assessed the value of immune-PDX mouse models for predicting responses to anti-PD-1 checkpoint inhibitor therapy in patients.Melanoma biopsies contained in a retrospective biobank were transplanted into NOG mice or NOG mice expressing interleukin 2 (hIL2-NOG mice). Tumor growth was monitored, and comparisons were made with clinical data, sequencing data, and current in silico predictive tools.Biopsies grew readily in NOG mice but growth was heterogeneous in hIL2-NOG mice. IL2 appears to activate T-cell immunity in the biopsies to block tumor growth. Biopsy growth in hIL2-NOG mice was negatively associated with survival in patients previously treated with PD-1 checkpoint blockade. In two cases, the prospective clinical decisions of anti-PD-1 therapy or targeted BRAF/MEK inhibitors were supported by the observed responses in mice.Immune-PDX models represent a promising addition to future biomarker discovery studies and for clinical decision making in patients receiving immunotherapy.
Impact of Body Mass Index (BMI) on Disease Free Survival and Likelihood of Pathologic Complete Response in Patients with Locally Advanced Breast Cancer Treated with Neoadjuvant Chemotherapy
Authors: A. Armengol-Alonso, A. Arance, M. Campayo, X. González-Farré, A. García-Herrera, P.L. Fernández, X. Caparros, I. Alonso, B. Farrus, M. Muñoz
Journal: Annals of Oncology (2012)
Number of Involved Organs is Predictive Factor of Response to Cyvadic Chemotherapy for Advanced Soft Tissue Sarcoma Patients
Authors: K. Nakano, S. Takahashi, N. Nishimura, Y. Mishima, S. Sakajiri, M. Yokoyama, Y. Terui, N. Motoi, K. Hatake
Journal: Annals of Oncology (2012)
Healthy lifestyle and life expectancy free of cancer, cardiovascular disease, and type 2 diabetes: prospective cohort study
Authors: Yanping Li, Josje Schoufour, Dong D Wang, Klodian Dhana, An Pan, Xiaoran Liu, Mingyang Song, Gang Liu, Hyun Joon Shin, Qi Sun, Laila Al-Shaar, Molin Wang, Eric B Rimm, Ellen Hertzmark, Meir J Stampfer, Walter C Willett, Oscar H Franco, Frank B Hu
Journal: BMJ (2020)

To examine how a healthy lifestyle is related to life expectancy that is free from major chronic diseases.Prospective cohort study.The Nurses' Health Study (1980-2014; n=73 196) and the Health Professionals Follow-Up Study (1986-2014; n=38 366).Five low risk lifestyle factors: never smoking, body mass index 18.5-24.9, moderate to vigorous physical activity (≥30 minutes/day), moderate alcohol intake (women: 5-15 g/day; men 5-30 g/day), and a higher diet quality score (upper 40%).Life expectancy free of diabetes, cardiovascular diseases, and cancer.The life expectancy free of diabetes, cardiovascular diseases, and cancer at age 50 was 23.7 years (95% confidence interval 22.6 to 24.7) for women who adopted no low risk lifestyle factors, in contrast to 34.4 years (33.1 to 35.5) for women who adopted four or five low risk factors. At age 50, the life expectancy free of any of these chronic diseases was 23.5 (22.3 to 24.7) years among men who adopted no low risk lifestyle factors and 31.1 (29.5 to 32.5) years in men who adopted four or five low risk lifestyle factors. For current male smokers who smoked heavily (≥15 cigarettes/day) or obese men and women (body mass index ≥30), their disease-free life expectancies accounted for the lowest proportion (≤75%) of total life expectancy at age 50.Adherence to a healthy lifestyle at mid-life is associated with a longer life expectancy free of major chronic diseases.
P-0070 Curcumin Inhibit the Epithelial–Mesenchymal Transition Induced by Hypoxia in Hepatocellular Carcinoma Cell Line HEPG2 in Vitro
Authors: Yuanhong Chang, Mei Jiang, Yi Wang, Caiqiao Yin, Ting Li, Jun Yin, Xuqi Li
Journal: Annals of Oncology (2012)
Impact of Chemotherapy Beyond the Third Line in Patients with Recurrent Epithelial Ovarian Cancer
Authors: L. Mansi, E. Kalbacher, M. Demarchi, F. Bazan, M. Schneider, A. Vuillemin, S. Bernhard, V. Nerich, C. Borg, X. Pivot
Journal: Annals of Oncology (2012)
Cytosine and adenine base editing of the brain, liver, retina, heart and skeletal muscle of mice via adeno-associated viruses
Authors: Jonathan M. Levy, Wei-Hsi Yeh, Nachiket Pendse, Jessie R. Davis, Erin Hennessey, Rossano Butcher, Luke W. Koblan, Jason Comander, Qin Liu, David R. Liu
Journal: Nature Biomedical Engineering (2020)
Anomalously warm temperatures are associated with increased injury deaths
Authors: Robbie M. Parks, James E. Bennett, Helen Tamura-Wicks, Vasilis Kontis, Ralf Toumi, Goodarz Danaei, Majid Ezzati
Journal: Nature Medicine (2020)

Temperatures that deviate from the long-term local norm affect human health, and are projected to become more frequent as the global climate changes1. There are limited data on how such anomalies affect deaths from injuries. In the present study, we used data on mortality and temperature over 38 years (1980-2017) in the contiguous USA and formulated a Bayesian spatio-temporal model to quantify how anomalous temperatures, defined as deviations of monthly temperature from the local average monthly temperature over the entire analysis period, affect deaths from unintentional (transport, falls and drownings) and intentional (assault and suicide) injuries, by age group and sex. We found that a 1.5 °C anomalously warm year, as envisioned under the Paris Climate Agreement2, would be associated with an estimated 1,601 (95% credible interval 1,430-1,776) additional injury deaths. Of these additional deaths, 84% would occur in males, mostly in adolescence to middle age. These would comprise increases in deaths from drownings, transport, assault and suicide, offset partly by a decline in deaths from falls in older ages. The findings demonstrate the need for targeted interventions against injuries during periods of anomalously warm temperatures, especially as these episodes are likely to increase with global climate change.
Randomized Phase II Study of Oxaliplatin and S-1 (OS) Versus Oxaliplatin and Capecitabine (XELOX) in Patients with Metastatic or Recurrent Colorectal Cancer
Authors: D.Y. Zang, I.J. Chung, H. Oh, K.U. Park, K.H. Lee, B. Han, D.R. Choi, H.S. Kim, J.H. Kim
Journal: Annals of Oncology (2012)
Soluble Interleukin 6 Receptor: A Serum Biomarker Predicting Preoperative Chemoradiotherapy Efficacy for Oesophageal Cancer
Authors: K. Kato, Y. Makuuchi, K. Honda, Y. Osaka, T. Kojima, K. Furuta, H. Igaki, H. Daiko, A. Tsuchida, T. Yamada
Journal: Annals of Oncology (2012)
Authors’ reply to Hunter
Authors: Matthew Harris, Mark Skopec, Hamdi Issa
Journal: BMJ (2020)

We agree with Hunter that patients’ demands and expectations can propel the diffusion of innovations.12 He suggests that adoption of the Ponseti technique in the UK was driven to some extent by patient demand, despite the longstanding experience and evidence from contexts in which it had been used extensively.345 Perhaps this was needed because techniques and innovations from these contexts are not taken …
Tryptophan Catabolism is Associated with the Prognosis of Patients with De Novo Acute Myeloid Leukemia
Authors: N. Nakamura, T. Hara, R. Mabuchi, J. Nagano, K. Ogawa, J. Kitagawa, N. Kanemura, N. Goto, H. Tsurumi, H. Moriwaki
Journal: Annals of Oncology (2012)
Clinical Outcome of advanced Gastric Cancer (GC) Patients Receiving First-Line Chemotherapy According to Tumour Histology and Location
Authors: A. Bittoni, M. Scartozzi, R. Giampieri, L. Faloppi, M. Bianconi, A. Mandolesi, M. Del Prete, M. Pistelli, I. Bearzi, S. Cascinu
Journal: Annals of Oncology (2012)
Biomarkers of Everolimus Efficacy in Patients with Metastatic Renal Cell Carcinoma (MRCC): Analysis of the Phase III Record-1 Trial
Authors: S. Oudard, B. Escudier, J. Thompson, V. Grünwald, P.F. Conte, S. Bracarda, A. Panneerselvam, S. Gogov, D. Chen, R.J. Motzer
Journal: Annals of Oncology (2012)
Epigenetic silencing of microRNA-125b-5p promotes liver fibrosis in nonalcoholic fatty liver disease via integrin α8-mediated activation of RhoA signaling pathway
Authors: Qingxian Cai, Fengjuan Chen, Fen Xu, Ke Wang, Ka Zhang, Guojun Li, Jun Chen, Hong Deng, Qing He
Journal: Metabolism (2020)
Device-Based Modulation of Neurocircuits as a Therapeutic for Psychiatric Disorders
Authors: Zhi-De Deng, Bruce Luber, Nicholas L. Balderston, Melbaliz Velez Afanador, Michelle M. Noh, Jeena Thomas, William C. Altekruse, Shannon L. Exley, Shriya Awasthi, Sarah H. Lisanby
Journal: The Annual Review of Pharmacology and Toxicology (2020)

Device-based neuromodulation of brain circuits is emerging as a promising new approach in the study and treatment of psychiatric disorders. This work presents recent advances in the development of tools for identifying neurocircuits as therapeutic targets and in tools for modulating neurocircuits. We review clinical evidence for the therapeutic efficacy of circuit modulation with a range of brain stimulation approaches, including subthreshold, subconvulsive, convulsive, and neurosurgical techniques. We further discuss strategies for enhancing the precision and efficacy of neuromodulatory techniques. Finally, we survey cutting-edge research in therapeutic circuit modulation using novel paradigms and next-generation devices.
Zinc supplementation ameliorates lung injury by reducing neutrophil recruitment and activity
Authors: Inga Wessels, Johanna Theresa Pupke, Klaus-Thilo von Trotha, Alexander Gombert, Anika Himmelsbach, Henrike Josephine Fischer, Michael J Jacobs, Lothar Rink, Jochen Grommes
Journal: Thorax (2020)

Zinc is well known for its anti-inflammatory effects, including regulation of migration and activity of polymorphonuclear neutrophils (PMN). Zinc deficiency is associated with inflammatory diseases such as acute lung injury (ALI). As deregulated neutrophil recruitment and their hyper-activation are hallmarks of ALI, benefits of zinc supplementation on the development of lipopolysaccharides (LPS)-induced ALI were tested.64 C57Bl/6 mice, split into eight groups, were injected with 30 µg zinc 24 hours before exposure to aerosolised LPS for 4 hours. Zinc homoeostasis was characterised measuring serum and lung zinc concentrations as well as metallothionein-1 expression. Recruitment of neutrophils to alveolar, interstitial and intravascular space was assessed using flow cytometry. To determine the extent of lung damage, permeability and histological changes and the influx of protein into the bronchoalveolar lavage fluid were measured. Inflammatory status and PMN activity were evaluated via tumour necrosis factor α levels and formation of neutrophil extracellular traps. The effects of zinc supplementation prior to LPS stimulation on activation of primary human granulocytes and integrity of human lung cell monolayers were assessed as well.Injecting zinc 24 hours prior to LPS-induced ALI indeed significantly decreased the recruitment of neutrophils to the lungs and prevented their hyperactivity and thus lung damage was decreased. Results from in vitro investigations using human cells suggest the transferability of the finding to human disease, which remains to be tested in more detail.Zinc supplementation attenuated LPS-induced lung injury in a murine ALI model. Thus, the usage of zinc-based strategies should be considered to prevent detrimental consequences of respiratory infection and lung damage in risk groups.
P3.13 Immune Status Stratification of Metastatic Breast Cancer Patients: Lympho-Divpenia Predicts Overall Survival
Authors: M. Manuarii, O. Tredan, T. Bachelot, G. Clapisson, A. Courtier, G. Parmentier, T. Rabeony, A. Grives, S. Perez, J.F. Mouret, D. Perol, S. Chabaud, I. Ray-Coquard, I. Labidi-Galy, P. Heudel, J.Y. Pierga, C. Caux, J.Y. Blay, N. Pasqual, C. Ménétrier-Caux
Journal: Annals of Oncology (2012)
US drug companies pledge to keep price rises “reasonable” as legislators try to rein in costs
Authors: Ingrid Torjesen
Journal: BMJ (2020)

Leaders in the pharmaceutical and biotechnology industries have signed a commitment to pricing that enables “broad” and “uninterrupted” patient access in the face of action from US lawmakers to drive down prescription costs.

The New Commitment to Patients pledges “to achieve broad patient access” to products at launch through a pricing structure that reflects “innovation and value,” and to ensure any subsequent price rises are “reasonable and guided by the need for uninterrupted patient access.” It adds that industry “will collaborate with policymakers, pharmacy, benefit managers, payers, and providers to find ways to limit or eliminate copays and deductibles for all patients.”

The commitment was drafted by the chief executives of Alnylam Pharmaceuticals, Amicus Therapeutics, Global Blood Therapeutics, GlycoMimetics, Nkarta Therapeutics, …
Phase I/II Study of NC-6004, A Novel Micellar Formulation of Cisplatin, In Combination with Gemcitabine in Patients with Pancreatic Cancer in Asia - Results of Phase I
Authors: W. Su, L. Chen, C. Li, J. Chen, Y. Lin, S. Choo, Y. Matsumura
Journal: Annals of Oncology (2012)
Fungicide Residues Exposure and β-amyloid Aggregation in a Mouse Model of Alzheimer’s Disease
Authors: Pierre-André Lafon, Yunyun Wang, Margarita Arango-Lievano, Joan Torrent, Lucie Salvador-Prince, Marine Mansuy, Nadine Mestre-Francès, Laurent Givalois, Jianfeng Liu, Josep Vicent Mercader, Freddy Jeanneteau, Catherine Desrumaux, Véronique Perrier
Journal: Environmental Health Perspectives (2020)

Background: Pesticide residues have contaminated our environment and nutrition over the last century. Although these compounds are present at very low concentrations, their long-term effects on human health is of concern. The link between pesticide residues and Alzheimer’s disease is not clear and difficult to establish. To date, no in&nbsp;vivo experiments have yet modeled the impact of this chronic contamination on neurodegenerative disorders. Objectives: We investigated the impact of fungicide residues on the pathological markers of Alzheimer’s disease in a transgenic mouse model. Methods: Transgenic (J20, hAPPSw/Ind) mice were chronically exposed to a cocktail of residues of cyprodinil, mepanipyrim, and pyrimethanil at 0.1μg/L in their drinking water for 9 months. We assessed the effects of fungicide residues on the pathological markers of the disease including Aβ aggregates, neuroinflammation, and neuronal loss. Then, we studied the dynamics of Aβ aggregation in&nbsp;vivo via a longitudinal study using two-photon microscopy. Finally, we investigated the molecular mechanisms involved in the production and clearance of Aβ peptides. Results: We found that a chronic exposure to three fungicide residues exacerbated aggregation, microgliosis, and neuronal loss. These fungicides also increased vascular amyloid aggregates reminiscent of cerebral amyloid angiopathy between 6 and 9 months of treatment. The mechanism of action revealed that fungicides promoted Aβ peptide fibril formation in vitro and involved an in&nbsp;vivo overexpression of the levels of the β-secretase–cleaving enzyme (BACE1) combined with impairment of Aβ clearance through neprylisin (NEP). Conclusions: Chronic exposure of the J20 mouse model of Alzheimer’s disease to a cocktail of fungicides, at the regulatory concentration allowed in tap water (0.1μg/L), strengthened the preexisting pathological markers: neuroinflammation, Aβ aggregation, and APP β-processing. We hypothesize prevention strategies toward pesticide long-term exposure may be an alternative to counterbalance the lack of treatment and to slow down the worldwide Alzheimer’s epidemic. https://doi.org/10.1289/EHP5550