tbuckley/cabot-search huggingface dataset:
Germline EGFR mutation is uncommon and plays a limited role in predisposition to lung cancer
Authors: Issan Tam, Lai Leung, Lap Chung, Maria Wong
Journal: Cancer Research (2007)

LB-131   Tyrosine kinase inhibitor (TKI) treatment directed against epidermal growth factor receptor (EGFR) has led to dramatic clinical benefits in a group of lung cancer patients - Asian, non-smoking women with adenocarcinoma (AD). Lung cancers associated with this clinical pathological profile often demonstrate somatic EGFR mutations. Our previous study has shown that EGFR mutations are common in our population, involving >50% of all adenocarcinomas and >70% of those from non-smokers, while EGFR double mutations occur in an unusually high proportion of about 13% of untreated lung cancers. Subcloning experiments infer that the double mutations are in cis to each other, occurring on the same allele. These double mutations include a known activating mutation together with an uncommon single amino acid substitution such as T790M. T790M can be occasionally induced as a second mutation in lung cancers previously treated by TKI. It has also been reported as a germline mutation in a family that predisposes to multiple bronchioloalveolar carcinoma formation, in some cases in the presence of an additional somatic activating mutation in cis to T790M. This raises the speculation that in our untreated lung cancers bearing double EGFR mutations, that the uncommon mutant could also be a germline change that predisposes to an activating mutant in cis to itself. We therefore investigated for the possibility of germline EGFR mutations in our population. We screened for 5 mutations (T790M, E709A, E709K, L858M and G873E) found in our lung cancer cases that involved only as one of double mutants but never as the sole mutation in lung adenocarcinomas. 670 alleles from the peripheral mononuclear cells of 335 lung cancer patients were screened. Only one germline mutation, G873E, was found, together with somatic delE746_S752insVP in the tumor. This suggested that germline EGFR mutation is uncommon, and plays a limited role in lung cancer pathogenesis in our population.
Early Weight Loss during Chemoradiotherapy Has a Detrimental Impact on Outcome in NSCLC
Authors: Karin J.C. Sanders, Lizza E. Hendriks, Esther G.C. Troost, Gerben P. Bootsma, Ruud M.A. Houben, Annemie M.W.J. Schols, Anne-Marie C. Dingemans
Journal: Journal of Thoracic Oncology (2016)
Lung Cancer Presenting With Solitary Bone Metastases
Authors: Pasi A. Jänne, Milton W. Datta, Bruce E. Johnson
Journal: Journal of Clinical Oncology (1999)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1999.17.9.2998 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10561378 Lung Cancer Presenting With Solitary Bone Metastases Pasi A. JännexPasi A. JänneSearch for articles by this author , Milton W. DattaxMilton W. DattaSearch for articles by this author , Bruce E. JohnsonxBruce E. JohnsonSearch for articles by this author Show More Lowe Center for Thoracic Oncology, Department of Adult Oncology, Dana Farber Cancer Institute, and Departments of Pathology and Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA https://doi.org/10.1200/JCO.1999.17.9.2998 First Page Full Text PDF Figures and Tables © 1999 by American Society of Clinical Oncology
OC-073 Evidence for genetic contribution to plasticity of the human swallowing motor system: the role of<i>BDNF</i>polymorphism
Authors: V Jayasekeran, N Pendleton, G Holland, A Payton, S Jefferson, B Ollier, M Horan, J Rothwell, S Hamdy
Journal: Gut (2010)

<h3>Introduction</h3> A single nucleotide polymorphism (SNP) of brain-derived neurotrophic factor (<i>BDNF</i>) gene has been shown to influence neurological function. Transcranial magnetic stimulation (TMS) studies have suggested that the <i>BDNF</i> SNP producing a valine to methionine substitution can modulate plasticity in human motor cortex.12 This study aimed to determine if the SNP influences the outcome of two excitatory forms of neurostimulation applied to the swallowing motor system. <h3>Methods</h3> Healthy subjects (n=22, 6 males, mean age 59) with predetermined <i>BDNF</i> SNP status (Val/Val or non-Val/Val), underwent bi-hemispheric single pulse TMS measurements of pharyngeal EMG responses recorded from a swallowed intra luminal catheter to assess corticobulbar excitability. Following baseline assessment with TMS, subjects received either pharyngeal electrical stimulation (PES) at 5 Hz, 75% of sensory threshold, for 10 minutes (n=16, 9 Val/Val and 7 non-Val/Val) or 250 pulses of 5 Hz repetitive TMS (rTMS) over the dominant pharyngeal motor cortex (n=22, 15 Val/Val and 7 non-Val/Val). Repeated measurements of the cortical excitability were assessed with TMS up to 60 minutes following the two interventions. Pharyngeal motor cortical excitability for the 2 <i>BDNF</i> SNP genotypes was compared using 2-way ANOVA. <h3>Results</h3> PES significantly increased the amplitude of pharyngeal motor evoked potentials (MEPs) in the Val/Val group compared to the non-Val/Val group with a strong Genotype*Time interaction (<i>F</i><sub>8112</sub>=2.4, p=0.018) (see Abstract 21). By contrast, there was a significant reduction in latencies of the non-Val/Val group after 5 Hz rTMS (Genotype∗Time interaction, <i>F</i><sub>3,60</sub>=4.9, p=0.04). There was no significant difference in MEP latencies between groups following PES. <h3>Conclusion</h3> SNPs of the <i>BDNF</i> gene predicts the degree of plasticity in the human swallowing motor system to differing forms of neurostimulation. Our results suggest that therapeutic response to swallowing interventions in pathology such as dysphagic stroke may be guided by <i>BDNF</i> genotype profiling.
Inducing labour in older women does not increase complications, study finds
Authors: Susan Mayor
Journal: BMJ (2016)

Pregnant women aged 35 and older who have their labour induced have no higher risk of caesarean section or other maternal or neonatal adverse outcomes than those who wait until spontaneous onset of labour, shows a UK study published in the New England Journal of Medicine .1

The risk of stillbirth, hypertensive disease, gestational diabetes mellitus, and placenta praevia are all higher in pregnant women over 35. Inducing labour at or before the due date may be beneficial in this age group, because 38 weeks is the gestational age at …
The pulmonary endothelium in acute respiratory distress syndrome: insights and therapeutic opportunities
Authors: Fraser R Millar, Charlotte Summers, Mark J Griffiths, Mark R Toshner, Alastair G Proudfoot
Journal: Thorax (2016)

The pulmonary endothelium is a dynamic, metabolically active layer of squamous endothelial cells ideally placed to mediate key processes involved in lung homoeostasis. Many of these are disrupted in acute respiratory distress syndrome (ARDS), a syndrome with appreciable mortality and no effective pharmacotherapy. In this review, we consider the role of the pulmonary endothelium as a key modulator and orchestrator of ARDS, highlighting advances in our understanding of endothelial pathobiology and their implications for the development of endothelial-targeted therapeutics including cell-based therapies. We also discuss mechanisms to facilitate the translation of preclinical data into effective therapies including the application of biomarkers to phenotype patients with ARDS with a predominance of endothelial injury and emerging biotechnologies that could enhance delivery, discovery and testing of lung endothelial-specific therapeutics.
Myoglobinuric acute renal failure in the rat
Authors: S N Heyman, S Rosen, S Fuchs, F H Epstein, M Brezis
Journal: Journal of the American Society of Nephrology (1996)

Myoglobin induces renal injury by mechanisms that remain incompletely defined. In this study, the effects of myoglobin upon renal microcirculation, oxygenation, morphology, and function were investigated in anesthetized rats, and the contribution of coexisting perturbations to myoglobin nephrotoxicity were evaluated. Myoglobin infusion (3.3 mg/min) reduced outer medullary blood flow and Po2, whereas renal blood flow and cortical Po2 were unaffected. Myoglobin infusion (38 mg/100 g weight over 45 min) induced renal failure associated with collecting duct and medullary thick ascending limb dilation and casts, with focal tubular damage, confined mainly to the superficial cortex. Preconditioning with indomethacin, I-N-monomethyl arginine, and theophylline reduced cortical superficial damage but enhanced injury within the inner stripe of the outer medulla and in medullary rays, the zones of lowest O2 supply. In preconditioned animals, tubulorrhexis was primarily observed in collecting ducts transversing the inner stripe, and was remarkably reminiscent of human descriptions (J. Oliver et al., J Clin Invest 1951; 30: 1307-1440). Deterioration in kidney function closely correlated with morphologic features of both tubular obstruction and necrosis. In conclusion, medullary vasoconstriction and intrarenal hypoxia may play a role in myoglobin-induced renal failure. The deterioration in kidney function appears to reflect the combined effects of cortical damage, medullary hypoxic injury, and tubular obstruction.
Ocular manifestations in churg-strauss syndrome: a case of inflammatory pseudotumor of superior rectus muscle
Authors: G. Murgia, D. Firinu, S. Del Giacco, M. Pisanu, L. Serusi, M. Lorrai, R. Meleddu, M. Peralta, A. Frau, F. Musu, P. Manconi
Journal: Allergy (2012)
Evidence for Mechanisms Underlying the Functional Benefits of a Myocardial Matrix Hydrogel for Post-MI Treatment
Authors: Jean W. Wassenaar, Roberto Gaetani, Julian J. Garcia, Rebecca L. Braden, Colin G. Luo, Diane Huang, Anthony N. DeMaria, Jeffrey H. Omens, Karen L. Christman
Journal: Journal of the American College of Cardiology (2016)
Use of bevacizumab to facilitate up-front chemoradiation in poor-risk patients with glioblastoma multiforme by improving neurologic function.
Authors: R. M. Green, E. A. Woyshner, L. Nghiemphu, A. Lai, T. Cloughesy
Journal: Journal of Clinical Oncology (2010)

2059 Background: Poor postoperative neurologic function due to mass effect and steroid-refractory perilesional edema often limits the ability of patients with glioblastoma multiforme (GBM) to tolerate standard radiation therapy (RT) and temozolomide (TMZ). Methods: We retrospectively analyzed the records of 12 patients with GBM and poor neurologic function (Karnofsky Performance Status [KPS] < 60%) due to bulky disease whom we treated with bevacizumab (bev) in the up-front setting in an attempt to improve their ability to tolerate chemoradiation. Results: The median age was 71 years; 6 patients were male, 6 were female. All patients received TMZ 75 mg/sq m/d for 42 d, followed by 150-200 mg/sq m/d for 5 of every 28 d; bev was given at a dose of 5 mg/kg every 2 weeks. Bev was initiated prior to RT in 8 patients and during RT in 2 patients; 2 patients did not initiate RT. Nine of the 12 patients (75%) were able to complete RT: standard regional 6,000 cGy (3), hypofractionated regional (4), and whole brain (2). One patient died soon after initiating RT, 1 died prior to RT, and 1 patient is currently awaiting RT. Ten patients were available for clinical examination 2 months after bev initiation. The median KPS improved from 50 to 70% and the median dex dose reduced from 12 to 4 mg daily. Of 11 patients with post-bev MR scans, 5 (45%) showed a partial response, 4 (35%) a minor response, 1 (10%) stable disease, and 1 (10%) possible progression. Complications included deep venous thrombosis (2), pneumonia (3), and asymptomatic intratumoral hemorrhage (1). Median time to progression was 5.2 months (95% CI 0.9-8.9) and median overall survival was 8 months (95% CI 2.3-13) from the date of surgery. Conclusions: The addition of bev to standard chemoradiation in patients with GBM and bulky cerebral tumors with KPS < 60% led to a tumor response in the majority of patients, rapidly improved neurologic function, reduced steroid requirements, and allowed a majority of patients to complete definitive RT. A phase II study of up-front bevacizumab in this poor prognostic subgroup of GBM is warranted. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech
Production of Casein and the Presence of Estrogen Receptors in Human Breast Cancer 2
Authors: A. Pich, G. Bussolati, F. DiCarlo
Journal: JNCI Journal of the National Cancer Institute (1977)

The relationship between the presence of estrogen receptors and casein (evaluated on a semiquantitative basis with a specific immunofluorescence method) was statistically analyzed in 50 cases of human breast carcinomas. No significant correlation was found between these two parameters, whereas a relationship was established between the production of casein and the degree of histological differentiation. The results of this study, like those of other studies, revealed a lack of correlation between the presence of estrogen receptors and the degree of histologic differentiation.
Randomized Phase Ii Trial Avareg (Ml25739) with Bevacizumab (Bev) or Fotemustine (Ftm) in Recurrent Gbm: Final Results from the Randomized Phase Ii Trial
Authors: A. Brandes, G. Finocchiaro, V. Zagonel, A. Fabi, C. Caserta, M. Reni, M. Clavarezza, E. Maiello, G. Carteni, G. Rosti, M. Eoli, G. Lombardi, M. Monteforte, R. Agati, V. Eusebi, A. Galli, S. Doria, E. Franceschi
Journal: Annals of Oncology (2014)
P-139 Efficacy of a Sequential Treatment Strategy with GEMOX Followed by FOLFIRI in Advanced Cholangiocarcinoma
Authors: S. Sebbagh, J. Roux, C. Dreyer, C. Neuzillet, A. de Gramont, C. Orbegoso, O. Hentic, P. Hammel, A. de Gramont, E. Raymond, T. André, B. Chibaudel, S. Faivre
Journal: Annals of Oncology (2015)
Abstract 18324: The Innate Immune System, Nlrp3 Inflammasome is Intensified in Epicardial Adipose Tissue around Coronary Arterial Lesions: Evidence from Biopsied Adipose Tissue in Coronary Artery Bypass Surgery
Authors: Hiromi Sato, Michio Shimabukuro, Yoichiro Hirata, Minoru Tabata, Dagvasumberel Munkhbaatar, Daiju Fukuda, Hirotsugu Kurobe, Takeshi Soeki, Shuichiro Takanashi, Tetsuya Kitagawa, Masataka Sata
Journal: Circulation (2012)

Background: The emergence of chronic inflammation could enhance obesity-induced insulin resistance and atherosclerosis, but the underlying mechanisms remain unclear. The Nod-like receptor (NLR) family of innate immune cell sensors, such as pyrin domain-containing-3 (NLRP3) inflammasome are implicated as one candidate to elicit nonmicrobial originated signals in atherosclerosis. Objectives: We determined association between the NLRP3 inflammasome signals in epicardial adipose tissue (EAT) and coronary atherosclerosis in human. Method: Pair samples were obtained from epicardial and subcutaneous adipose tissue during elective cardiac surgery for coronary (CAD, n=40) or non-coronary artery disease (non-CAD, n=40). Expression of NLRP3 in EAT was analyzed by immunohistochemical staining using antibodies against NLRP3, CD68 and IL18. Expression of pro- and anti-inflammatory adipocytokines in EAT was evaluated by quantitative real-time polymerase chain reaction (qPCR). Results: By immunohistochemical staining, NLRP3 signals were well detected in EAT of the CAD group, but rarely in EAT of the non-CAD group. The signals was co-localized with macrophages in EAT determined by anti-CD68 or anti-F4/80 immunostaining. By qPCR, signals of NLRp3, TLR1, TLR2, TLR4, but not TLR3, TLR5 and TLR9, were increased in EAT of the CAD group as compared to that of the non-CAD group. Signals of MyD88, but not MD-2, were also enhanced in EAT of the CAD group. Signals of IL-18 and adiponectin were decreased in EAT of the CAD group. Conclusions: We, for the first time, showed that NLRP3 inflammasome signals were enhanced, but signals of IL-18 and adiponectin were decreased, in EAT of the coronary atherosclerotic lesions. We conclude that atherogenesis in human coronary arteries may be caused in part by NLR signals in infiltrating macrophage of epicardial adipose tissue.
Genome-wide association study of gastric adenocarcinoma in Asia: a comparison of associations between cardia and non-cardia tumours
Authors: Nan Hu, Zhaoming Wang, Xin Song, Lixuan Wei, Byung Sik Kim, Neal D Freedman, Jiwon Baek, Laurie Burdette, Jiang Chang, Charles Chung, Sanford M Dawsey, Ti Ding, Yu-Tang Gao, Carol Giffen, Yaling Han, Myunghee Hong, Jia Huang, Hee Sung Kim, Woon-Puay Koh, Linda M Liao, Yi Min Mao, You-Lin Qiao, Xiao-Ou Shu, Wen Tan, Chaoyu Wang, Chen Wu, Min-Jie Wu, Yong-Bing Xiang, Meredith Yeager, Jeong Hwan Yook, Jian-Min Yuan, Peng Zhang, Xue-Ke Zhao, Wei Zheng, Kyuyoung Song, Li-Dong Wang, Dongxin Lin, Stephen J Chanock, Alisa M Goldstein, Philip R Taylor, Christian C Abnet
Journal: Gut (2015)

Genome-wide association studies (GWAS) of gastric cancer have reported differences in single-nucleotide polymorphism (SNP) associations for tumour subtypes, particularly when divided by location into the gastric cardia versus the non-cardia.Here we present results for a GWAS using 2350 East Asian gastric cancer cases divided as 1189 gastric cardia and 1027 gastric non-cardia cases and 2708 controls. We also included up to 3042 cardia cases, 4359 non-cardia cases and 7548 controls for replication from two Chinese studies and one Korean study. From the GWAS, we selected 12 top SNPs for each gastric cancer subtype, 4 top SNPs for total gastric cancer and 1 SNP in MUC1 for replication testing.We observed genome-wide significant associations for rs10074991 in PRKAA1 at 5p13.1 for cardia (p=7.36×10(-12)) and non-cardia cancers (p=2.42×10(-23)) with per allele OR (95% CI) for the combined endpoint of 0.80 (0.77 to 0.83). At 6p21.1, rs2294693 near UNC5CL was significantly associated with gastric non-cardia cancer risk (p=2.50×10(-8)), with OR (95% CI) of 1.18 (1.12 to 1.26), but there was only a nominal association for cardia cancer (p=1.47×10(-2)). We also confirmed a previously reported association for rs4072037 in MUC1 with p=6.59×10(-8) for total gastric cancer and similar estimates for cardia and non-cardia cancers. Three SNPs in PSCA previously reported to be associated with gastric non-cardia cancer showed no apparent association for cardia cancer.Our results suggest that associations for SNPs with gastric cancer show some different results by tumour location in the stomach.
Olympus to pay $646m to settle charges over device sales
Authors: Michael McCarthy
Journal: BMJ (2016)

Olympus Corporation of the Americas, the largest distributor of endoscopes in the US, has agreed to pay $646 million (£459m; €594m) to resolve criminal charges and civil claims related to a scheme to pay kickbacks to doctors and hospitals in the US and Latin America that bought the company’s products, the US Department of Justice announced on 1 March. Under a three year deferred prosecution agreement, the company will be able to avoid conviction if it complies with reform and compliance requirements.

In a statement, Olympus acknowledged the company’s responsibility for …
Birth Spacing and Risk of Adverse Perinatal Outcomes
Authors: Agustin Conde-Agudelo, Anyeli Rosas-Bermúdez, Ana Cecilia Kafury-Goeta
Journal: JAMA (2006)

ContextBoth short and long interpregnancy intervals have been associated with an increased risk of adverse perinatal outcomes. However, whether this possible association is confounded by maternal characteristics or socioeconomic status is uncertain.ObjectiveTo examine the association between birth spacing and relative risk of adverse perinatal outcomes.Data SourcesStudies published in any language were retrieved by searching MEDLINE (1966 through January 2006), EMBASE, ECLA, POPLINE, CINAHL, and LILACS, proceedings of meetings on birth spacing, and bibliographies of retrieved articles, and by contact with relevant researchers in the field.Study SelectionIncluded studies were cohort, cross-sectional, and case-control studies with results adjusted for at least maternal age and socioeconomic status, reporting risk estimates and 95% confidence intervals (or data to calculate them) of birth spacing and perinatal outcomes. Of 130 articles identified in the search, 67 (52%) were included.Data ExtractionInformation on study design, participant characteristics, measure of birth spacing used, measures of outcome, control for potential confounding factors, and risk estimates was abstracted independently by 2 investigators using a standardized protocol.Data SynthesisA random-effects model and meta-regression analyses were used to pool data from individual studies. Compared with interpregnancy intervals of 18 to 23 months, interpregnancy intervals shorter than 6 months were associated with increased risks of preterm birth, low birth weight, and small for gestational age (pooled adjusted odds ratios [95% confidence intervals]: 1.40 [1.24-1.58], 1.61 [1.39-1.86], and 1.26 [1.18-1.33], respectively). Intervals of 6 to 17 months and longer than 59 months were also associated with a significantly greater risk for the 3 adverse perinatal outcomes.ConclusionsInterpregnancy intervals shorter than 18 months and longer than 59 months are significantly associated with increased risk of adverse perinatal outcomes. These data suggest that spacing pregnancies appropriately could help prevent such adverse perinatal outcomes.
Chromosome Banding Patterns of Two Transplantable Pituitary Tumors Induced in Rats by 2,4,6-Trimethylaniline2
Authors: Joseph Kovi, Harold P. Morris, Elizabeth Kovi
Journal: JNCI Journal of the National Cancer Institute (1977)

The chromosomal constitution of a mammosomatotrophic and an inactive transplantable pituitary tumor induced in rats by 2,4,6-trimethylaniline was studied by the Giemsa-banding techniques. The inactive tumor line 7315i evolved from the active tumor line 7315a in one of the early transfers. A comparison was also made with the chromosomal patterns of a transplantable rat hepatoma (7316A) induced by the same chemical carcinogen. Pituitary tumor line 7315a had a pseudotriploid complement with 63 chromosomes, whereas the inactive line 7315i was hypodiploid, with a dominant stemline of 36 chromosomes. The stemline chromosome number of the hepatoma was in the hypotetraploid region. Giemsa banding revealed that all chromosomes of the normal rat complement were present in both pituitary tumors. Four abnormal chromosomes were detected in the active tumor line and three in the inactive line. Both tumor lines contained a single minute chromosome. One common marker, a deleted chromosome #1, was found in both pituitary tumors. This common marker chromosome was, however, not present in the hepatoma. The stemline karyotype of the hepatoma contained seven different markers, but none of them was identical to the abnormal chromosomes of the pituitary neoplasms. The findings suggested that the abnormal karyotypes of lines 7315a and 7315i could reflect the multisecretory activities of these neoplastic pituitary cells but that chromosomal localization of the secretory defect awaits exact genetic mapping of the rat chromosomes.