tbuckley/cabot-search huggingface dataset:
Updated analysis of SWOG 0023: A randomized phase III trial of gefitinib versus placebo maintenance after definitive chemoradiation followed by docetaxel in patients with locally advanced stage III non-small cell lung cancer
Authors: K. Kelly, K. Chansky, L. E. Gaspar, J. R. Jett, Y. Ung, K. S. Albain, J. J. Crowley, D. R. Gandara
Journal: Journal of Clinical Oncology (2007)

7513 Background: Early clinical studies with gefitinib (G) showed promising efficacy and mild toxicity in patients (pts) with advanced NSCLC. Thus, G was an ideal agent to evaluate in a maintenance setting in stage III disease following definitive treatment. Methods: Untreated pts with stage III NSCLC, a PS of 0–1 and adequate organ function were eligible. Patients received the SWOG 9504 core regimen (cisplatin 50 mg/m 2 , d1 &amp; 8 plus etoposide 50 mg/m 2 day 1–5, every 28 days for 2 cycles with concurrent thoracic radiation, 1.8–2 Gy fractions/day, total dose 61 Gy, followed by 3 cycles of docetaxel 75 mg/m 2 ). Non- progressing pts were randomized to G 250 mg per day or placebo (P) until disease progression, intolerable toxicity or 5 years. The planned sample size was 672, to confer power of 0.89 to detect a 33% increase over the expected median survival of 21 months (one-sided 0.025 level logrank test). Randomization was stratified by stage and histology. Results: Enrollment began in July 2001. An unplanned interim analysis prompted by outside data was conducted in April 2005 and the alternative hypothesis of improved survival was rejected at the 0.0015 level for 243 randomized patients. The study closed and preliminary results were reported (ASCO 2005). Now with a median follow up of 27 months, median survival for the G arm (n=118) was 23 months and was 35 months for the P arm (n=125) (two sided p=0.013). Overall survival for the 571eligible patients was 19 months. ≥ Grade 3 toxicities in the G arm were rash (7%), diarrhea (7%) and pneumonitis (3%). Conclusion: In this unselected population G did not improve survival. Decreased survival was due to cancer not G toxicity. Three year survival estimates will be presented. Molecular studies of the EGFR pathway are underway and will be correlated with outcomes. No significant financial relationships to disclose.
Effects of Tissue Culture Environment on Growth Patterns and Ultrastructure of Poorly Differentiated Human Cervical Carcinomas2
Authors: N. Auersperg, H. Erber
Journal: JNCI Journal of the National Cancer Institute (1976)

Growth patterns and ultrastructure were compared between biopsy specimens and primary cultures of poorly differentiated carcinomas of the human uterine cervix. Though not obvious histologically, all carcinomas in vivo retained ultrastructural traits of squamous, glandular, or basal cell differentiation. Carcinomas with squamous traits grew as compact masses in vivo and formed cohesive colonies in vitro; tumors with basal and glandular traits infiltrated host tissues in a dispersed fashion, but their growth patterns in vitro were variable and unpredictable. The growth patterns of mixed carcinomas, in which squamous and glandular characteristics were evident in the same cells, generally resembled those of tumors with squamous traits. The levels of differentiation in vitro exceeded those found in vivo: Tonofilaments, desmosomes, and glycogen aggregations (squamous traits) as well as secretory vesicles, endoplasmic reticulum, and cilia (grandular traits) became more numerous and complex in culture. The direction of differentiation, expressed in vivo, usually persisted in vitro, through squamous traits appeared de novo or became more prominent when some of the tumors were explanted. The enhancement of differentiation by the culture environment indicated that the cervical carcinomas did not express their full potential to differentiate when growing in the natural host. The coexistence of squamous and glandular traits in the same cells and the capacity of tumors to shift from a glandular to a squamous differentiative pathway upon explantation support the concept that cervical carcinomas originate in bipotential cells, i.e, either reserve cells or metaplastic basal cells derived from the glandular epithelium.
Reduced Cardiac Index Is Not the Dominant Driver of Renal Dysfunction in Heart Failure
Authors: Jennifer S. Hanberg, Krishna Sury, F. Perry Wilson, Meredith A. Brisco, Tariq Ahmad, Jozine M. ter Maaten, J. Samuel Broughton, Mahlet Assefa, W.H. Wilson Tang, Chirag R. Parikh, Jeffrey M. Testani
Journal: Journal of the American College of Cardiology (2016)
Liver-Directed Radiotherapy for Hepatocellular Carcinoma
Authors: Florence K. Keane, Jennifer Y. Wo, Andrew X. Zhu, Theodore S. Hong
Journal: Liver Cancer (2016)

&lt;b&gt;&lt;i&gt;Background: &lt;/i&gt;&lt;/b&gt;The incidence of hepatocellular carcinoma (HCC) continues to increase world-wide. Many patients present with advanced disease with extensive local tumor or vascular invasion and are not candidates for traditionally curative therapies such as orthotopic liver transplantation (OLT) or resection. Radiotherapy (RT) was historically limited by its inability to deliver a tumoricidal dose; however, modern RT techniques have prompted renewed interest in the use of liver-directed RT to treat patients with primary hepatic malignancies. &lt;b&gt;&lt;i&gt;Summary: &lt;/i&gt;&lt;/b&gt;The aim of this review was to discuss the use of external beam RT in the treatment of HCC, with particular focus on the use of stereotactic body radiotherapy (SBRT). We review the intricacies of SBRT treatment planning and delivery. Liver-directed RT involves accurate target identification, precise and reproducible patient immobilization, and assessment of target and organ motion. We also summarize the published data on liver-directed RT, and demonstrate that it is associated with excellent local control and survival rates, particularly in patients who are not candidates for OLT or resection. &lt;b&gt;&lt;i&gt;Key Messages:&lt;/i&gt;&lt;/b&gt; Modern liver-directed RT is safe and effective for the treatment of HCC, particularly in patients who are not candidates for OLT or resection. Liver-directed RT, including SBRT, depends on accurate target identification, precise and reproducible patient immobilization, and assessment of target and organ motion. Further prospective studies are needed to fully delineate the role of liver-directed RT in the treatment of HCC.
Can we identify patients at risk of life‐threatening allergic reactions to food?
Authors: P. J. Turner, J. L. Baumert, K. Beyer, R. J. Boyle, C.‐H. Chan, A. T. Clark, R. W. R. Crevel, A. DunnGalvin, M. Fernández‐Rivas, M. H. Gowland, L. Grabenhenrich, S. Hardy, G. F. Houben, J. O'B Hourihane, A. Muraro, L. K. Poulsen, K. Pyrz, B. C. Remington, S. Schnadt, R. van Ree, C. Venter, M. Worm, E. N. C. Mills, G. Roberts, B. K. Ballmer‐Weber
Journal: Allergy (2016)

Abstract Anaphylaxis has been defined as a ‘severe, life‐threatening generalized or systemic hypersensitivity reaction’. However, data indicate that the vast majority of food‐triggered anaphylactic reactions are not life‐threatening. Nonetheless, severe life‐threatening reactions do occur and are unpredictable. We discuss the concepts surrounding perceptions of severe, life‐threatening allergic reactions to food by different stakeholders, with particular reference to the inclusion of clinical severity as a factor in allergy and allergen risk management. We review the evidence regarding factors that might be used to identify those at most risk of severe allergic reactions to food, and the consequences of misinformation in this regard. For example, a significant proportion of food‐allergic children also have asthma, yet almost none will experience a fatal food‐allergic reaction; asthma is not, in itself, a strong predictor for fatal anaphylaxis. The relationship between dose of allergen exposure and symptom severity is unclear. While dose appears to be a risk factor in at least a subgroup of patients, studies report that individuals with prior anaphylaxis do not have a lower eliciting dose than those reporting previous mild reactions. It is therefore important to consider severity and sensitivity as separate factors, as a highly sensitive individual will not necessarily experience severe symptoms during an allergic reaction. We identify the knowledge gaps that need to be addressed to improve our ability to better identify those most at risk of severe food‐induced allergic reactions.
Clinical iron deficiency disturbs normal human responses to hypoxia
Authors: Matthew C. Frise, Hung-Yuan Cheng, Annabel H. Nickol, M. Kate Curtis, Karen A. Pollard, David J. Roberts, Peter J. Ratcliffe, Keith L. Dorrington, Peter A. Robbins
Journal: Journal of Clinical Investigation (2016)

Iron bioavailability has been identified as a factor that influences cellular hypoxia sensing, putatively via an action on the hypoxia-inducible factor (HIF) pathway. We therefore hypothesized that clinical iron deficiency would disturb integrated human responses to hypoxia.We performed a prospective, controlled, observational study of the effects of iron status on hypoxic pulmonary hypertension. Individuals with absolute iron deficiency (ID) and an iron-replete (IR) control group were exposed to two 6-hour periods of isocapnic hypoxia. The second hypoxic exposure was preceded by i.v. infusion of iron. Pulmonary artery systolic pressure (PASP) was serially assessed with Doppler echocardiography.Thirteen ID individuals completed the study and were age- and sex-matched with controls. PASP did not differ by group or study day before each hypoxic exposure. During the first 6-hour hypoxic exposure, the rise in PASP was 6.2 mmHg greater in the ID group (absolute rises 16.1 and 10.7 mmHg, respectively; 95% CI for difference, 2.7-9.7 mmHg, P = 0.001). Intravenous iron attenuated the PASP rise in both groups; however, the effect was greater in ID participants than in controls (absolute reductions 11.1 and 6.8 mmHg, respectively; 95% CI for difference in change, -8.3 to -0.3 mmHg, P = 0.035). Serum erythropoietin responses to hypoxia also differed between groups.Clinical iron deficiency disturbs normal responses to hypoxia, as evidenced by exaggerated hypoxic pulmonary hypertension that is reversed by subsequent iron administration. Disturbed hypoxia sensing and signaling provides a mechanism through which iron deficiency may be detrimental to human health.ClinicalTrials.gov (NCT01847352).M.C. Frise is the recipient of a British Heart Foundation Clinical Research Training Fellowship (FS/14/48/30828). K.L. Dorrington is supported by the Dunhill Medical Trust (R178/1110). D.J. Roberts was supported by R&D funding from National Health Service (NHS) Blood and Transplant and a National Institute for Health Research (NIHR) Programme grant (RP-PG-0310-1004). This research was funded by the NIHR Oxford Biomedical Research Centre Programme.
Myelodysplastic Syndrome Marrow Stroma Shows Widespread Aberrant Hypermethylation That Is Abrogated By Treatment with Dnmt Inhibitors
Authors: Tushar D Bhagat, Matthias Bartenstein, Yiting Yu, A. Mario Q. Marcondes, Britta Will, Orsolya Giricz, Davendra P. Sohal, Ioannis Mantzaris, Amittha Wickrema, Christine Mcmahon, Yeung Cecilia, John Greally, Siddhartha Mukherjee, Ulrich Steidl, H. Joachim Deeg, Amit Verma
Journal: Blood (2014)
Abstract IA04: Clinical decision support in the era of genome informed cancer medicine
Authors: Mia Levy
Journal: Cancer Research (2015)

Abstract The emergence of high throughput genomic testing of tumors presents both an opportunity and challenge for use in clinical decision making across the continuum of cancer care. A tsunami of molecular data is now reaching the clinic with variable levels of evidence with respect to clinical validity and clinical utility. Not surprising, a large knowledge gap remains for oncologists who try to apply this new data for clinical decisions at the point of care. In order to address this knowledge gap, we have developed My Cancer Genome (MCG), a publically available website with the mission to curate and disseminate knowledge regarding the clinical significance of genomic alterations in cancer. My cancer genome contains content curated by domain experts on the prognostic and therapeutic implications of genomic alterations in cancers, including experimental therapeutics and active clinical trials. In addition to being publically available via MyCancerGenome.org, the content has also been integrated into a decision support tool for interpretation and reporting of results for tumor next generation sequencing via a commercial partner. Opportunities to scale resources like MCG continue to present opportunities and challenges to the cancer community. Data driven approaches where we learn from the experience of all cancer patients will be needed to help realize the promise of precision cancer medicine. Citation Format: Mia Levy. Clinical decision support in the era of genome informed cancer medicine. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr IA04.
Curcumin bioavailability from oil in water nano-emulsions: In vitro and in vivo study on the dimensional, compositional and interactional dependence
Authors: Raffaele Vecchione, Vincenzo Quagliariello, Dominic Calabria, Vincenzo Calcagno, Elisa De Luca, Rosario V. Iaffaioli, Paolo A. Netti
Journal: Journal of Controlled Release (2016)
A phase I dose escalation trial of MAGE-A3 and HPV-16 specific peptide immunomodulatory vaccines in patients with recurrent/metastatic (RM) squamous cell carcinoma of the head and neck (SCCHN).
Authors: Dan Paul Zandberg, Sandra Rollins, Olga G. Goloubeva, Robert E Morales, Ming Tony Tan, Rodney Taylor, Jeffrey S Wolf, Kevin J. Cullen, Ann Zimrin, Robert Ord, Joshua E Lubek, John C Papadimitriou, Dean Mann, Scott E Strome, Martin J. Edelman
Journal: Journal of Clinical Oncology (2014)

e17014 Background: New therapeutic modalities are needed for RM-SCCHN. We conducted a phase I dose escalation study to evaluate the safety and immunologic response to peptide immunomodulatory vaccines GL-0810 (HPV16) and GL-0817 (MAGE-A3) in HPV16 and MAGE-A3 positive SCCHN patients (pts) respectively. Methods: Pts >18 years old, and ECOG PS 0-2, with RM-SCCHN incurable with standard treatments with tumor expression of HPV16 or MAGE-A3 were eligible. Three dose levels (500 µg, 1000 µg, 1500 µg) of GL-0810 or GL-0817 with adjuvants Montanide (1.2ml) and GM-CSF (100µg/m2) were given sq q2 weeks for a total of 4 vaccinations. Vaccine specific T cell and antibody response were measured by IFN-γ ELISPOT and ELISA respectively. Results: 9 pts were enrolled in the HPV16 cohort and 7 pts in the MAGE-A3 cohort with 63% having received at least 1 prior palliative chemotherapy regimen. The study was closed early due to insufficient accrual. In the HPV16 cohort, 3 pts were vaccinated at each dose level. In the MAGE-A3 cohort 3 pts were vaccinated at 500µg and 1000µg and 1 pt at 1500µg . No dose limiting toxicity was observed and toxicity was predominantly local and grade 1 (erythema, pain, and itching at the injection site). 5 patients progressed before completing vaccinations. In those that received all 4 vaccinations, 80% (4/5) of the HPV16 cohort, and 67% (4/6) of the MAGE-A3 cohort developed a T cell and antibody response. Evaluation using the exact McNemar test showed significant concordance between T cell and antibody responses for both groups, with T cell responses usually preceding antibody responses. No clear dose-response correlation was seen. All pts progressed by RECIST at first repeat imaging, except for one pt in the MAGE-A3 500µg cohort who had stable disease for 10.5 mo. The median PFS and OS for the MAGE-A3 cohorts were 79 and 183 days respectively and for the HPV16 cohort 80 days and 196 days respectively. Conclusions: (1) GL-0810 and GL-0817 were well tolerated in pts with RM-SCCHN. (2) T cell and antibody responses were observed in the majority of pts who received 4 vaccinations. (3) Further testing in an adjuvant setting is indicated. Clinical trial information: NCT00257738.
Case 9-1990
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, H.L. Corwin, J.F. Southern
Journal: New England Journal of Medicine (1990)

Presentation of CaseA 39-year-old man was admitted to the hospital because of left-sided abdominal pain, malignant hypertension, and proteinuria.The patient was in excellent health until 27 days earlier, when he experienced the acute onset of pain in the left upper abdominal quadrant. He was seen at another hospital, where an x-ray film of the chest was reported to be normal. The pain resolved in three hours, and the patient was discharged.Five days later severe pain recurred in the left upper abdominal quadrant, was "knife-like," and radiated slightly to the left side of the midabdomen; nausea and vomiting . . .
Non-small cell lung cancer and estrogen plus progestin use in postmenopausal women in the Women's Health Initiative randomized clinical trial
Authors: R. T. Chlebowski, A. Schwartz, H. Wakelee, G. L. Anderson, M. L. Stefanick, J. E. Manson, J. W. Chien, C. Chen, J. Wactawski-Wende, M. Gass
Journal: Journal of Clinical Oncology (2009)

CRA1500 The full, final text of this abstract will be available in Part II of the 2009 ASCO Annual Meeting Proceedings, distributed onsite at the Meeting on May 30, 2009, and as a supplement to the June 20, 2009, issue of the Journal of Clinical Oncology. [Table: see text]
Case 26-2000
Authors: Harold J. Wanebo, Rhonda K. Yantiss
Journal: New England Journal of Medicine (2000)

Presentation of CaseA 47-year-old man was admitted to the hospital because of recurrent abdominal pain and a pancreatic lesion.The patient had been well until about seven months earlier, when his stools became loose, with intermittent hematochezia. Biopsy specimens of the rectum and colon obtained at 30 and 60 cm during sigmoidoscopic examination revealed active chronic colitis, for which mesalamine was prescribed. Five months before admission, the treatment was discontinued for an uncertain reason. Two weeks later, the patient had the first of four bouts of intense upper abdominal pain and vomiting, each of which lasted about 24 hours. . . .
Response to Comment by Faurby, Werdelin and Svenning
Authors: Stephen J. O’Brien, Klaus Peter Koepfli, Eduardo Eizirik, Warren Johnson, Carlos Driscoll, Agostinho Antunes, Anne Schmidt-Kuntzel, Laurie Marker, Pavel Dobrynin
Journal: Genome biology (2016)

Faurby, Werdelin, and Svenning raise some interesting and valid points around the interpretation of the genomics and fossil data on the history of the African cheetah, a species that has fascinated humankind for millennia.They emphasize a controversy to which we alluded in our article [1] and they offer an alternative explanation to the scenario we had suggested for the time and place of demographic events that preceded modern African cheetah populations.We fully agree that there are important areas of uncertainty in this conundrum and welcome the opportunity to reconsider and to offer our view into the natural history of Acinonyx jubatus.We do believe that the integration of fossil and molecular data seems a good way to get toward the truth, so we shall try to emphasize two considerations in our comments: first, the most parsimonious interpretation of data; and second, the robustness of available and relevant fossil and molecular data.
Safety and tolerability of acetylcysteine and pirfenidone combination therapy in idiopathic pulmonary fibrosis: a randomised, double-blind, placebo-controlled, phase 2 trial
Authors: Jürgen Behr, Elisabeth Bendstrup, Bruno Crestani, Andreas Günther, Horst Olschewski, C Magnus Sköld, Athol Wells, Wim Wuyts, Dirk Koschel, Michael Kreuter, Benoît Wallaert, Chin-Yu Lin, Jürgen Beck, Carlo Albera
Journal: The Lancet Respiratory Medicine (2016)
Organophosphate Insecticide Metabolites in Prenatal and Childhood Urine Samples and Intelligence Scores at 6 Years of Age: Results from the Mother–Child PELAGIE Cohort (France)
Authors: Chloé Cartier, Charline Warembourg, Gaïd Le Maner-Idrissi, Agnès Lacroix, Florence Rouget, Christine Monfort, Gwendolina Limon, Gaël Durand, Dave Saint-Amour, Sylvaine Cordier, Cécile Chevrier
Journal: Environmental Health Perspectives (2015)

Background:Several studies suggest that exposure to organophosphate insecticides (OP) during pregnancy impairs neurodevelopment in children.Objectives:We evaluated associations between biomarkers of prenatal and postnatal OP exposure and cognitive function of 6-year-olds in a French longitudinal birth cohort.Methods:In 2002–2006, the PELAGIE mother–child cohort enrolled pregnant women from Brittany. For a random subcohort, we measured nonspecific dialkylphosphate metabolites (DAP) of OP in one maternal urine sample, collected before 19 weeks' gestation, and in one urine sample collected from their 6-year-old children. Six subtests of the Wechsler Intelligence Scale for Children, 4th edition (WISC-IV) were administered when the children were 6 years of age to evaluate cognitive function (n = 231). Linear regression models controlling for factors including maternal intelligence and the Home Observation for Measurement of the Environment score were used.Results:WISC-IV scores were not significantly associated with prenatal or childhood total DAP metabolites. WISC verbal comprehension score was significantly higher in association with the highest maternal urinary concentrations of diethylphosphate (DE) metabolites (5.5; 95% CI: 0.8, 10.3 for > 13.2 nmol/L vs. < LOQ), whereas WISC working memory score was significantly lower in association with the highest urinary concentrations of DE metabolites at age 6 years (–3.6; 95% CI: –7.8, –0.6 for > 11.1 nmol/L vs. < LOD).Conclusion:We found no evidence that prenatal OP exposure adversely affected cognitive function in 6-year-olds, perhaps because of the population's socioeconomic status, which was higher than in previous studies, though other causal and noncausal explanations are also possible. The negative association between WISC score and concurrent DE urinary concentrations requires replication by longitudinal studies investigating childhood OP exposure.Citation:Cartier C, Warembourg C, Le Maner-Idrissi G, Lacroix A, Rouget F, Monfort C, Limon G, Durand G, Saint-Amour D, Cordier S, Chevrier C. 2016. Organophosphate insecticide metabolites in prenatal and childhood urine samples and intelligence scores at 6 years of age: results from the mother–child PELAGIE cohort (France). Environ Health Perspect 124:674–680; http://dx.doi.org/10.1289/ehp.1409472