tbuckley/cabot-search huggingface dataset:
Linifanib phase II trial in patients with advanced hepatocellular carcinoma (HCC).
Authors: H. Toh, P. Chen, B. I. Carr, J. J. Knox, S. Gill, J. Qian, Q. Qin, J. L. Ricker, D. M. Carlson, W. Yong
Journal: Journal of Clinical Oncology (2010)

4038 Background: Linifanib (ABT-869), a novel potent and selective inhibitor of the VEGF and PDGF platelet-derived growth factor families of RTKs, is designed to inhibit angiogenesis, tumor growth, and metastasis. Methods: This was an open-label, multicenter trial of oral linifanib 0.25 mg/kg QD in Child-Pugh A (C-PA) or QOD in Child-Pugh B (C-PB) patients (pts) until progressive disease (PD) or intolerable toxicity. Key eligibility included unresectable or metastatic HCC; ≥1 prior systemic therapy; at least one measurable lesion by CT scan. Endpoints were progression free (PF) rate at 16 weeks (primary) and ORR, time to progression (TTP), time to radiographic progression (TTPr), OS (secondary). Results: 44 pts were enrolled from 09/07 to 08/08, 84% received no prior systemic therapy. Median age was 62 y (range 20-81). Most common linifanib-related AEs were fatigue (55%) and diarrhea (48%). Most common linifanib-related grade 3 or 4 AEs (NCI toxicity criteria) were hypertension (HT, 18%) and fatigue (14%). 68% of pts had dose interruptions due to AEs; most common reasons included HT (18%) and proteinuria (11%), which were reversible. 34% of pts required dose reductions due to AEs. As of 11/09, 4 pts (CP-A) remained on study. 27 pts had discontinued due to PD (clinical, radiographic, or AE related to PD), 8 due to AEs not related to PD, and 5 for other reasons. There was one death possibly related to linifanib (intracranial hemorrhage, Day 111, CP-B). Serum protein induced by vitamin K absence (PIVKA) was decreased in 11 of 33 evaluable pts on study and was associated with improved OS. Conclusions: Linifanib is clinically active in advanced HCC (C-PA), with an acceptable safety profile. A phase III study of linifanib vs sorafenib in this setting is ongoing. Point estimate (95% CI) CP-A n=38 CP-B n=6 All N=44 PF rate at 16 weeks (%) 34.2 (19.6, 51.4) 16.7 (0.4, 64.1) 31.8 (18.6, 47.6) ORR* (%) 7.9 (1.7, 21.4) 0 6.8 (1.4, 18.7) TTP** (mo) 5.4 (3.6, 14.1) 3.7 (0.7, NR) 3.7 (3.6, 7.3) TTPr** (mo) 5.4 (3.6, NR) NR (3.7, NR) 5.4 (3.6, NR) OS** (mo) 10.4 (8.4, 14.9) 2.5 (1.1, 4.5) 9.7 (6.3, 12.2) Abbreviation: NR, not reached. Results based on radiographic (central imaging center) and clinical (investigator) assessments. * Per RECIST. Responses confirmed on 2 visits >4 weeks apart. ** Estimated median. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abbott Laboratories Medigene Abbott Laboratories Bristol-Myers Squibb, GlaxoSmithKline, Merck
Paradoxical decrease in isoprostane and increase in superoxide dismutase following CPAP withdrawal in OSA
Authors: Charalambos Antoniades, Regent Lee, Malcolm Kohler, John Stradling
Journal: European Respiratory Journal (2016)

We thank Monneret and Bonnefont-Rousselot for their commentary. Our controlled trial design overcomes most of their concerns; any failure of assay techniques would not have produced a biased result, but in fact would have decreased the chances of finding any between-group effects. In our study we observed a statistically significant decrease in urinary F2-isoprostanes following the withdrawal of continuous positive airway pressure (CPAP) treatment in patients with obstructive sleep apnoea (OSA), in a randomised, 2-week trial, where those involved in the assays were entirely blind to group allocation [1]. In addition to this unexpected result, we observed no significant change in any plasma marker of oxidative stress we measured in this population (malondialdehyde and lipid hydroperoxides) or even the production of superoxide radicals by peripheral blood mononuclear cells. It is important to note that these were morning measurements. Paradoxical decrease in isoprostane and increase in superoxide dismutase following CPAP withdrawal in OSA <http://ow.ly/UcgYP>
Frequent detection of Epstein-Barr virus DNA by the polymerase chain reaction in lymph node biopsies from patients with Hodgkin's disease without genomic evidence of B- or T-cell clonality
Authors: H Knecht, BF Odermatt, E Bachmann, S Teixeira, R Sahli, D Hayoz, P Heitz, F Bachmann
Journal: Blood (1991)
Figures have risen by over 150% over 10 years
Authors: B. A Sides
Journal: BMJ (1996)

tosis, actinic keratoses, and non-melanoma skin cancers, which are all objective indicators of excess exposure to the sun.3Studies of migrants to Australia clearly implicate exposure to the sun in early childhood as a major risk factor for the development of melanoma.4British studies have identified large numbers of benign melanocytic naevi as the main independent risk factor for melanoma.'These observations have led to studies aimed at determining the main risk factors for developing naevi, one of which is expo- sure to the sun in early childhood.Thus the case for excess exposure to ultraviolet radiation as a major risk factor for cutaneous malignant melanoma is established.More work is needed to define the relevant wavelengths of the spectrum and the exact quantity of ultraviolet radiation experienced by individuals of different phenotypes that lead to individual high risk.The pathogenesis of sunbum is also unclear, yet no one doubts the causal role of exposure to the sun.2Aetiological studies of melanoma over the long term should not be confused with current studies aimed at improving the nomenclature of early inva- sive malignant melanoma.
Commentary The hospital component of vocational training for general practice
Authors: T J Bayley
Journal: BMJ (1994)

Trainees and educationalists in general practice have some grounds for suggesting that the hospital component of vocational training should be restructured and teaching improved. However, the implications for other trainees and secondary care have to be considered. Changes that are needed include a curriculum for senior house officers in each specialty; appointment of training consultants with the necessary skills; and a different attitude by everyone towards study leave, including arrangements for funding. The optimum duration of hospital posts for trainees in general practice might be shorter than now, but the effects on others must be considered and competencies guaranteed in a briefer training period. Changes in the regulations for vocational training could help to improve specialist experience if trainees in general practice were allowed to be supernumerary. Alternatively, senior house officer posts for trainees in general practice could be split between secondary and primary care, thus encouraging a broader perspective.
A Preclinical Model for ERα-Positive Breast Cancer Points to the Epithelial Microenvironment as Determinant of Luminal Phenotype and Hormone Response
Authors: George Sflomos, Valerian Dormoy, Tauno Metsalu, Rachel Jeitziner, Laura Battista, Valentina Scabia, Wassim Raffoul, Jean-Francois Delaloye, Assya Treboux, Maryse Fiche, Jaak Vilo, Ayyakkannu Ayyanan, Cathrin Brisken
Journal: Cancer Cell (2016)
A randomized clinical trial of neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the oesophagus or gastro-oesophageal junction
Authors: F. Klevebro, G. Alexandersson von Döbeln, N. Wang, G. Johnsen, A.-B. Jacobsen, S. Friesland, I. Hatlevoll, N.I. Glenjen, P. Lind, J.A. Tsai, L. Lundell, M. Nilsson
Journal: Annals of Oncology (2016)
Type 1 diabetes is associated with increased risk of several cancers
Authors: Jacqui Wise
Journal: BMJ (2016)

People with type 1 diabetes have a higher incidence of cancer of the liver, pancreas, kidney, endometrium, and ovary and a lower incidence of prostate cancer than the general population, an analysis of diabetes registers across five countries has shown.1

Previous research has found that people with diabetes have a 20-25% higher incidence of cancer than people without diabetes, but most studies have looked at type 2 diabetes.

Researchers analysed data from nationwide diabetes registers in Australia (2000-08), Denmark (1995-2014), Finland (1972-2012), Scotland (1995-2012), and Sweden (1987-2012). They found 9149 cases of …
Long-term outcomes and prognostic factors of skull-base chondrosarcoma patients treated with pencil-beam scanning proton therapy at the Paul Scherrer Institute
Authors: Damien C. Weber, Shahed Badiyan, Robert Malyapa, Francesca Albertini, Alessandra Bolsi, Antony J. Lomax, Ralf Schneider
Journal: Neuro-Oncology (2015)

Skull-base chondrosarcoma (ChSa) is a rare disease, and the prognostication of this disease entity is ill defined.We assessed the long-term local control (LC) results, overall survival (OS), and prognostic factors of skull-base ChSa patients treated with pencil beam scanning proton therapy (PBS PT). Seventy-seven (male, 35; 46%) patients with histologically confirmed ChSa were treated at the Paul Scherrer Institute. Median age was 38.9 years (range, 10.2-70.0y). Median delivered dose was 70.0 GyRBE (range, 64.0-76.0 GyRBE). LC, OS, and toxicity-free survival (TFS) rates were calculated using the Kaplan Meier method.After a mean follow-up of 69.2 months (range, 4.6-190.8 mo), 6 local (7.8%) failures were observed, 2 of which were late failures. Five (6.5%) patients died. The actuarial 8-year LC and OS were 89.7% and 93.5%, respectively. Tumor volume > 25 cm(3) (P = .02), brainstem/optic apparatus compression at the time of PT (P = .04) and age >30 years (P = .08) were associated with lower rates of LC. High-grade (≥3) radiation-induced toxicity was observed in 6 (7.8%) patients. The 8-year high-grade TFS was 90.8%. A higher rate of high-grade toxicity was observed for older patients (P = .073), those with larger tumor volume (P = .069), and those treated with 5 weekly fractions (P = .069).This is the largest PT series reporting the outcome of patients with low-grade ChSa of the skull base treated with PBS only. Our data indicate that protons are both safe and effective. Tumor volume, brainstem/optic apparatus compression, and age were prognosticators of local failures.
Abstract 122: PARK2 is a negative regulator of Wnt and EGFR pathways in glioma
Authors: Liang Xu, De-Chen Lin, Ye Chen, Haiyan Yan, Masaharu Hazawa, Ngan Doan, Jonathan W. Said, Ling-Wen Ding, Li-Zhen Liu, Henry Yang, Shi-zhu Yu, Michael Kahn, Dong Yin, Phillip Koeffler
Journal: Cancer Research (2015)

Abstract PARK2 is an E3 ubiquitin ligase whose dysfunction has been associated with the progression of autosomal recessive juvenile Parkinson's disease and human malignancies. However, its role in cancer remains to be explored. In this study, we report that PARK2 is frequently deleted and underexpressed in human glioma, and low PARK2 expression is associated with poor survival in cohorts of both low-grade glioma and glioblastoma multiforme (GBM). Functional studies revealed a tumor-suppressive role of PARK2 in GBM cells. Restoration of PARK2 significantly inhibited glioma cell growth both in vitro and in vivo, while depletion of endogenous PARK2 promoted cell proliferation. cDNA microarray analysis showed that PARK2 expression strongly altered the activity of both the Wnt and EGFR pathways. Immunoblot analysis confirmed that ectopic expression of PARK2 suppressed the intracellular levels of β-catenin, EGFR, as well as their down-stream targets including Cyclin D1, TCF4, c-Myc, p-AKT and p-S6K, etc. Notably, PARK2 physically interacted with both β-catenin and EGFR, and promoted their ubiquitination in an E3-ligase dependent manner. Similar to the ligase-dead PARK2 mutant (C431S), three PARK2 mutants harboring cancer-derived somatic mutations (T173A, T240M and P294S) showed decreased ability to ubiquitinate either β-catenin or EGFR proteins. We further found that PARK2 attenuated the cellular response to both Wnt3a and EGF stimulation, suggesting PARK2 is a negative regulator of both the Wnt and EGFR pathways. Lastly, inspired by these newly identified functions of PARK2, we tested and proved that the combination of small-molecule inhibitors targeting both Wnt-β-catenin and EGFR-AKT pathways synergistically impaired glioma cell viability. In aggregate, our findings uncover novel, cancer-associated functions of PARK2 and provide a potential therapeutic approach to treat glioma. Citation Format: Liang Xu, De-Chen Lin, Ye Chen, Haiyan Yan, Masaharu Hazawa, Ngan Doan, Jonathan W. Said, Ling-Wen Ding, Li-Zhen Liu, Henry Yang, Shi-zhu Yu, Michael Kahn, Dong Yin, Phillip Koeffler. PARK2 is a negative regulator of Wnt and EGFR pathways in glioma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 122. doi:10.1158/1538-7445.AM2015-122
Abstract P313: Excessive Daytime Sleepiness in Older British Men: An Early Marker of Heart Failure
Authors: Shahrzad Zonoozi, Sheena Ramsay, Olia Papacosta, Lucy Lennon, Elizabeth A Ellins, Julian P Halcox, Peter H Whincup, Sasiwarang G Wannamethee
Journal: Circulation (2016)

Background: Sleep disturbance is common, especially amongst older adults. The association between night-time sleep duration, cardiovascular disease (CVD), metabolic disorders and mortality has been extensively reported, with studies showing a U-shaped association. Less is known about the influence of daytime sleep and attention has more recently turned to excessive daytime sleepiness which has been associated with increased CVD, heart failure and mortality. We aimed to investigate the association between sleep patterns and cardiovascular risk markers in older adults including metabolic risk markers, cardiac markers and early markers of atherosclerosis [arterial stiffness and carotid intima-media thickness (CIMT)] with particular focus on day sleep. Methods: Cross sectional study of 1722 surviving men aged 71-92 examined in 2010-2012 across 24 British towns, from a prospective study initiated in 1978-1980. Men with a history of heart attack or heart failure (n = 251) were excluded from the analysis. Self-reported sleep duration (night and day) was based on a questionnaire; insomnia was defined as self-reported difficulty falling asleep. Participants were invited for a physical examination which included non-invasive assessment of vascular measures including CIMT and arterial stiffness (carotid distensibility and pulse wave velocity (PWV)). Results: Analysis of the data confirmed previous reports of a U-shaped association between night-time sleep duration and HbA1c, even following adjustment for confounding factors including age, BMI, physical activity and social class. Men who reported insomnia had significantly higher mean triglyceride, glucose and insulin (p = 0.02, 0.04 and 0.01 in the age-adjusted model). Increasing daytime sleep duration was associated with higher fasting glucose and insulin levels which remained significant (p = 0.02 and 0.01 respectively) after adjustment for prevalent diabetes. Compared to those with no daytime sleep, men with daytime sleep &gt; 1 hour had a higher risk of raised N-terminal pro brain natriuretic peptide (NT-proBNP) of ≥400pg/ml, the diagnostic threshold for heart failure [OR (95% CI) = 1.88 (1.15, 3.1)], reduced lung function (forced expiratory volume in 1s) and elevated von Willebrand factor (vWF), a marker of endothelial dysfunction. These patterns were not seen for night-time sleep or insomnia. Sleeping patterns were unrelated to CIMT and arterial stiffness. Conclusions: Day sleep of &gt; 1 hour may be an early indicator of heart failure. Clinically, this is important in the assessment of older patients who seek medical advice for excessive daytime sleepiness, in whom indicators of heart failure should be sought and further investigations carried out if necessary.
Comprehensive genomic analysis of malignant pleural mesothelioma identifies recurrent mutations, gene fusions and splicing alterations
Authors: Raphael Bueno, Eric W Stawiski, Leonard D Goldstein, Steffen Durinck, Assunta De Rienzo, Zora Modrusan, Florian Gnad, Thong T Nguyen, Bijay S Jaiswal, Lucian R Chirieac, Daniele Sciaranghella, Nhien Dao, Corinne E Gustafson, Kiara J Munir, Jason A Hackney, Amitabha Chaudhuri, Ravi Gupta, Joseph Guillory, Karen Toy, Connie Ha, Ying-Jiun Chen, Jeremy Stinson, Subhra Chaudhuri, Na Zhang, Thomas D Wu, David J Sugarbaker, Frederic J de Sauvage, William G Richards, Somasekar Seshagiri
Journal: Nature Genetics (2016)
Genomic approaches for understanding dengue: insights from the virus, vector, and host
Authors: Shuzhen Sim, Martin L. Hibberd
Journal: Genome biology (2016)

The incidence and geographic range of dengue have increased dramatically in recent decades. Climate change, rapid urbanization and increased global travel have facilitated the spread of both efficient mosquito vectors and the four dengue virus serotypes between population centers. At the same time, significant advances in genomics approaches have provided insights into host-pathogen interactions, immunogenetics, and viral evolution in both humans and mosquitoes. Here, we review these advances and the innovative treatment and control strategies that they are inspiring.
Granulopoiesis Associated With the C3HBA Tumor in Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: S Lan, G Rettura, S M Levenson, E Seifter
Journal: JNCI Journal of the National Cancer Institute (1981)

Female C3H/HeJ mice were inoculated with syngeneic breast adenocarcinoma cells (C3HBA). A progressive neutrophilia developed as the tumors grew. A linear relationship was demonstrated between the tumor diameter and the extent of the neutrophilia. Local tumor excision caused a rapid fall (3 days) in the neutrophil count. Media conditioned with tumor cells, normal mouse kidney, and bone marrow of normal or tumor-bearing mice were prepared. Tumor cell-conditioned medium was found to have marked stimulating activity for granulocytic colony formation of mouse bone marrow cells. Sera from tumor-bearing mice also had colony-stimulating activity. This finding strongly suggested that the neutrophilia was caused by the release of a neutrophil-stimulating factor from the tumor.
Abstract 17210: Neuroglobin Overexpression Protects Against Myocardial Ischemia by Attenuation of Hypoxia Inducible Factor-1alpha Related Inflammatory Pathways
Authors: Bert R Everaert, Anne Boerekamps, Nadine de Nijs, Wendy Van Leuven, Silvia De Wilde, Jean-Pierre Timmermans, Christiaan J Vrints
Journal: Circulation (2012)
Temperature‐dependent impact of thermal aminolaevulinic acid photodynamic therapy on apoptosis and reactive oxygen species generation in human dermal fibroblasts
Authors: A. Mamalis, E. Koo, G.D. Sckisel, D.M. Siegel, J. Jagdeo
Journal: British Journal of Dermatology (2016)

Actinic keratoses (AKs) are generally accepted as common precursor lesions to invasive squamous cell carcinoma. Photodynamic therapy (PDT) is a common, in-office, field therapy modality used in the treatment of AKs. Clinical and laboratory observations have demonstrated that temperature modulation can affect PDT efficacy.To demonstrate thermal PDT increases apoptotic cell death, and to investigate the mechanistic role of reactive oxygen species (ROS) free radicals in an in vitro human skin fibroblast model.This study was completed using commercially available primary human skin fibroblasts treated with aminolaevulinic acid (ALA) at specific concentrations and controlled temperatures. Cell death, apoptosis and superoxide ROS levels were quantified.We found that thermal PDT with 0·5 mmol L(-1) ALA resulted in significant temperature-dependent increases in total apoptosis and superoxide ROS generation between 33 °C and 42 °C.Our results indicate that thermal PDT significantly increases apoptotic cell death through increased generation of superoxide ROS in a temperature-dependent manner.
Reply to A. Wong et al
Authors: Victoria L. Chiou, Mauricio Burotto
Journal: Journal of Clinical Oncology (2016)

We appreciate the insightful discussion of Wong et al 1 inspired by our recent commentary on pseudoprogression and immunerelated response in solid tumors. 2 Specific criteria for immunerelated responses have been created to capture the dynamic patterns of response observed in patients who have been treated with immunotherapeutic agents. 3Wong et al raise multiple questions about the challenging role of palliative care because increasing numbers of oncology patients receive these novel drugs near the end of life.Patients and practitioners continue to gain wider access to immunotherapeutic agents through numerous clinical trials.In addition, immune checkpoint inhibitors are now available outside clinical trials through drug approvals in selected tumor indications.These novel therapies, with distinct mechanisms of action and immune-related patterns of response, have opened the door for further critical conversations for patients with cancer.In this era of immuno-oncology, the concept of value in cancer care remains paramount. 4,5Patients and physicians pursue these new therapies in search of clinical efficacy-measured by alleviation of clinical symptoms, tumor regression, durability of response, and survival benefit.At the level of an individual patient and provider, the potential promise of these agents is constantly weighed alongside potential impacts on quality of life, including regular clinical assessments, physical adverse effects, and financial cost.At a broader level, societal determinations of costeffectiveness and medical resource allocation may also vary across different health systems and regions of the world. 6ncreasingly, patients remain active advocates when evaluating their treatment options.Whether they are early in their treatment courses or in advanced-stage disease, patients approach their provider teams for guidance when deciding whether to pursue novel and/or experimental therapies.Oncologists and palliative care providers perform a pivotal role in increasing awareness of immune-related patterns of response and guiding transitions to survivorship follow-up, next treatments, and supportive care.The rising numbers of patients treated on immunotherapy and emerging information about responders across solid tumor types will provide new knowledge about survivorship in this population.In the field of immunotherapy, there are many stakeholders.Together, clinicians, investigators, regulatory agencies, drug developers, and ultimately our patients, are driving important ongoing conversations to improve cancer care.
End Results in Cancer of the Lung: Comparison of Male and Female Patients
Authors: Connelly, Roger R., Cutler, Sidney J., Baylis, Paula
Journal: JNCI Journal of the National Cancer Institute (1966)

Journal Article End Results in Cancer of the Lung: Comparison of Male and Female Patients Get access Roger R. Connelly, Roger R. Connelly Biometry Branch, National Cancer Institute2, Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Sidney J. Cutler, Sidney J. Cutler Biometry Branch, National Cancer Institute2, Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Paula Baylis Paula Baylis Biometry Branch, National Cancer Institute2, Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 36, Issue 2, February 1966, Pages 277–287, https://doi.org/10.1093/jnci/36.2.277 Published: 01 February 1966 Article history Received: 10 June 1965 Published: 01 February 1966