tbuckley/cabot-search huggingface dataset:
Phase II randomized trial of erlotinib versus vinorelbine in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC) aged ≥70 years in Taiwan
Authors: Y. Chen, C. Tsai, J. Shih, R. Perng, J. Whang-Peng
Journal: Journal of Clinical Oncology (2009)

8051 Background: Epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors, such as erlotinib, are effective against NSCLC, especially in East Asian patients. Single-agent chemotherapy, such as vinorelbine, is an appropriate treatment choice for elderly patients. Oral vinorelbine is more convenient for elderly patients than intravenous vinorelbine. The primary objective of this study was to compare the response rate of chemo-naïve, elderly patients with advanced NSCLC treated with daily erlotinib versus oral vinorelbine. Methods: Chemo-naïve Taiwanese patients aged ≥70 years with advanced NSCLC were enrolled and randomized (stratified by histology, smoking status, ECOG performance status, and gender) to receive either oral erlotinib 150mg/day or oral vinorelbine (60mg/m 2 on days 1 and 8 of the first cycle and subsequently increased to 80mg/m 2 every 3 weeks in the absence of grade 2 adverse events). From February 2007 to July 2008, 116 patients were enrolled. Results: By October 2008, 77 enrolled patients (n = 37 for erlotinib; n = 40 for vinorelbine) had completed 6 cycles of study treatment and were available for efficacy and safety analyses. Objective response rates were 21.6% (8/37) with erlotinib and 12.8% (5/39) with vinorelbine [95% CI -0.09–0.24 for the difference in response rate between arms]. Disease control rate was 70.3% with erlotinib and 56.4% with vinorelbine [95% CI -0.09–0.34 for the difference in disease control rate between arms; p = 0.216). Median time to disease progression was 4.4 months [95% CI 4.1–5.4] with erlotinib, compared with 3.9 months [95% CI 2.4–6.9] with vinorelbine, p = 0.6069. The most common treatment-related toxicities were skin rash and diarrhea with erlotinib, and diarrhea and nausea with vinorelbine. Conclusions: Erlotinib is effective and well tolerated compared with oral vinorelbine in elderly, chemo-naïve, Taiwanese patients with NSCLC. Updated efficacy and safety data will be presented. [Table: see text]
Evaluating usefulness of ING1 expression in stroma as a prognostic biomarker in breast cancer.
Authors: Arash Nabbi, Satbir Thakur, Alexander C. Klimowicz, Karl Riabowol
Journal: Journal of Clinical Oncology (2015)

e11543 Background: INhibitor of Growth (ING) proteins are type II tumor suppressors that are frequently down-regulated in diverse cancer types, including the neoplastic transformation of breast tissue. The ING1 gene encodes multiple isoforms that have been shown to affect apoptosis, senescence and cell cycle. Recently, we reported that low levels of ING1 protein are correlated with metastasis in breast cancer patients. In the present study, we have used immunohistochemistry and an automated quantitative analysis (AQUA) technique to quantify ING1 expression in the tumor and stromal components of breast cancer tissue. Methods: We used the Calgary Tamoxifen Cohort, which contains 816 breast cancer patients, for this study. Cytokine profiling was done using immortalized human mammary fibroblasts (HMF3s) infected with adenoviral ING1a or GFP. To determine the activity of matrix metalloproteases MMP-1 and MMP-2, gelatin and casein zymography were performed, respectively. Three-dimensional culture was performed using ING1a or GFP infected HMF3s and MCF7 cells. Results: Higher expression of ING1 in stroma was associated with worse prognosis in breast cancer cohort. The predictive value of stromal ING1 was found to be more significant than established biomarkers such as HER2 and ER. An increase in the levels of G-CSF, GM-CSF and MIP-1a was observed. However, a significant decrease was found in pro-inflammatory cytokines such as IL-6, IL-8, PDGFA, PDGFB, VEGF and GRO in HMF3s cells upon ING1a overexpression. ING1a overexpression increased the metalloproteases (MMPs) levels and decreased the levels of MMP inhibitors (TIMPs). ING1a overexpressing HMF3s cells induced disorganization of breast cancer cell derived organoids. Conclusions: Our study indicates the role of ING1a in breast cancer stroma and its role in epithelial transformation and suggests ING1 as a novel prognostic biomarker in breast cancer.
Sustained virological response for 94% of people treated with low-cost, legally imported generic direct acting antivirals for hepatitis C: analysis of 1087 patients in 4 treatment programmes
Authors: J. Freeman, G. Khwairakpam, J. Dragunova, S. Golovin, J. Wang, A. Hill, V. Houghton-Price, R. Smith, R. Korologou-Linden, G. Jefferys
Journal: Journal of Hepatology (2017)
A Prospective Multicenter Open-Label Study of the Effectiveness of Epoetin Beta for Patients with Low/Intermediate-1-Risk Myelodysplastic Syndrome (MDS): A Preliminary Result
Authors: Suporn Chuncharunee, Nonglak Kanitsap, Tawatchai Suwanban, Archrob Khuhapinant, Noppacharn Uaprasert, Kanchana Chansung, Ekarat Rattarittamrong, Somchai Wongkhantee, Noppadol Siritanaratanakul, Lalita Norasetthada, Thanyaphong Na Nakorn, Chadchai Charnwiboonsri
Journal: Blood (2016)
Epstein–Barr Virus-Induced VEGF and GM-CSF Drive Nasopharyngeal Carcinoma Metastasis via Recruitment and Activation of Macrophages
Authors: Di Huang, Shi-Jian Song, Zi-Zhao Wu, Wei Wu, Xiu-Ying Cui, Jia-Ning Chen, Mu-Sheng Zeng, Shi-Cheng Su
Journal: Cancer Research (2017)

Chronic inflammation induced by persistent microbial infection plays an essential role in tumor progression. Although it is well documented that Epstein-Barr virus (EBV) infection is closely associated with nasopharyngeal carcinoma (NPC), how EBV-induced inflammation promotes NPC progression remains largely unknown. Here, we report that tumor infiltration of tumor-associated macrophages (TAM) and expression of CCL18, the cytokine preferentially secreted by TAM, closely correlate with serum EBV infection titers and tumor progression in two cohorts of NPC patients. In vitro, compared with EBV- NPC cell lines, EBV+ NPC cell lines exhibited superior capacity to attract monocytes and skew them to differentiate to a TAM-like phenotype. Cytokine profiling analysis revealed that NPC cells with active EBV replications recruited monocytes by VEGF and induced TAM by GM-CSF in an NF-κB-dependent manner. Reciprocally, TAM induced epithelial-mesenchymal transition and furthered NF-κB activation of tumor cells by CCL18. In humanized mice, NPC cells with active EBV replications exhibited increased metastasis, and neutralization of CCL18, GM-CSF, and VEGF significantly reduced metastasis. Collectively, our work defines a feed-forward loop between tumor cells and macrophages in NPC, which shows how metastatic potential can evolve concurrently with virus-induced chronic inflammation. Cancer Res; 77(13); 3591-604. ©2017 AACR.
IRIS 6-Year Follow-Up: Sustained Survival and Declining Annual Rate of Transformation in Patients with Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Treated with Imatinib.
Authors: Andreas Hochhaus, Brian J. Druker, Richard A. Larson, Stephen G. O’Brien, Insa Gathmann, Francois Guilhot
Journal: Blood (2007)
Phase I clinical study with photochemical internalisation, a novel technology for treatment of perihilar cholangiocarcinoma
Authors: R. Sturgess, D. Palmer, J. Trojan, A. Hoffmeister, B. Neu, S. Kasper, A. Dechêne, C. Jürgensen, J. Schirra, R. Jakobs, A. Høgset, L. Finnesand
Journal: Journal of Hepatology (2017)
Engineered 3D Cardiac Fibrotic Tissue to Study Fibrotic Remodeling
Authors: Amir Hossein Sadeghi, Su Ryon Shin, Janine C. Deddens, Giuseppe Fratta, Serena Mandla, Iman K. Yazdi, Gyan Prakash, Silvia Antona, Danilo Demarchi, Marc P. Buijsrogge, Joost P. G. Sluijter, Jesper Hjortnaes, Ali Khademhosseini
Journal: Advanced Healthcare Materials (2017)

Activation of cardiac fibroblasts into myofibroblasts is considered to play an essential role in cardiac remodeling and fibrosis. A limiting factor in studying this process is the spontaneous activation of cardiac fibroblasts when cultured on two‐dimensional (2D) culture plates. In this study, a simplified three‐dimensional (3D) hydrogel platform of contractile cardiac tissue, stimulated by transforming growth factor‐β1 (TGF‐β1), is presented to recapitulate a fibrogenic microenvironment. It is hypothesized that the quiescent state of cardiac fibroblasts can be maintained by mimicking the mechanical stiffness of native heart tissue. To test this hypothesis, a 3D cell culture model consisting of cardiomyocytes and cardiac fibroblasts encapsulated within a mechanically engineered gelatin methacryloyl hydrogel, is developed. The study shows that cardiac fibroblasts maintain their quiescent phenotype in mechanically tuned hydrogels. Additionally, treatment with a beta‐adrenergic agonist increases beating frequency, demonstrating physiologic‐like behavior of the heart constructs. Subsequently, quiescent cardiac fibroblasts within the constructs are activated by the exogenous addition of TGF‐β1. The expression of fibrotic protein markers (and the functional changes in mechanical stiffness) in the fibrotic‐like tissues are analyzed to validate the model. Overall, this 3D engineered culture model of contractile cardiac tissue enables controlled activation of cardiac fibroblasts, demonstrating the usability of this platform to study fibrotic remodeling.
Three-year efficacy and safety of tenofovir disoproxil fumarate monotherapy for multidrug-resistant chronic hepatitis B
Authors: S.Y. Kwon, Y.-S. Lim, Y.S. Lee, G.-Y. Gwak, K.S. Byun, Y.J. Kim, J. Choi, J. An, H.C. Lee, B.C. Yoo
Journal: Journal of Hepatology (2017)
Lung Metastases from Esophageal Granular Cell Tumor: An Undoubted Criterion for Malignancy
Authors: Isidro Machado, Julia Cruz, Estanislao Arana, Juan Carlos Peñalver-Cuesta, Miguel Arraras-Martínez, Javier Lavernia, Antonio Llombart-Bosch
Journal: Journal of Thoracic Oncology (2017)
No increase in graft fibrosis for hepatitis B surface antigen positive patients after liver transplantation using entecavir monotherapy
Authors: J.Y.Y. Fung, T. Wong, K. Chok, A. Chan, S.-L. Sin, K. Ng, T.-T. Cheung, J. Dai, W.-K. Seto, C.-L. Lai, M.-F. Yuen, C.-M. Lo
Journal: Journal of Hepatology (2017)
Extracellular matrix turnover is regulated in 3D disease-specific human liver scaffolds engineered with human hepatic stellate cells
Authors: D.J. Leeming, A. Telese, W. Al-Akkad, J. Day, T. Luong, D. Thorburn, K. Rombouts, M.J. Nielsen, M.A. Karsdal, G. Mazza, M. Pinzani
Journal: Journal of Hepatology (2017)
Age as a prognostic factor for recurrence in premenopausal breast cancer patients.
Authors: Antonia Perello, Gemma Clemente, Jose Duran, Bartomeu Colom, Carmen Garcias-Espana, Joan Torrecabota, Antoni Avella, Ramon Canet, Julio Rifa
Journal: Journal of Clinical Oncology (2012)

e11036 Background: It remains controversial if young age at diagnosis is an independent prognostic factor for recurrence in breast cancer (BC) patients. Data regarding recurrence with long-term follow-up in premenopausal women are sparse. The aim of the study was to compare the outcome of young patients (&lt;=39 years) with older premenopausal patients. Methods: We collected clinical and pathological data from an inception cohort of 241 premenopausal patients aged &lt;=50 years at diagnosis with stage I-III BC between January 2000 and December 2005 in a single institution. Disease-free survival (DFS) event was defined as time from diagnosis to local or distant recurrence, contralateral invasive BC or death from any cause. Kaplan-Meier curves and Cox model were used to analyze the covariable predictors for recurrence. Results: Median age was 43 years (range: 24-50) and median follow-up was 100 months (range: 72-137). Seventy seven patients (32%) were &lt;=39 and 164 (68%) &gt;39 years of age at diagnosis. Five and 10-year disease-free survival rate was 61 % and 48% respectively for the younger group and 77% and 74% for the older group (p&lt;0.001). In the univariate analysis the hazard ratio (HR) for recurrence in young patients was 2.16 (95%CI: 1.38-3.37) (p&lt; 0.001) Adjusting for T stage (&lt;=2 cm versus &gt;2 cm), N (negative versus positive nodes), Grade (grade 1-2 versus grade 3) and Hormonal Receptor status (positive versus negative), age less than 40 remains and independent prognostic factor for recurrence with an adjusted HR of 2.42 (95%CI: 1.42-4.10) (p&lt;0.001), and was the most important adverse independent predictor among the factors included in the model. Conclusions: BC patients younger than 40 years of age at diagnosis have worse prognosis than older premenopausal patients, and have an independent prognostic value for recurrence after adjusting for known prognostic factors.
John Richard Bernard John David Creer Harry Jacobs Morus Wyn Lloyd-Owen Paul Preston Lock Robert Douglas McIntyre
Authors: S C Illingworth
Journal: BMJ (1998)

# John Richard Bernard {#article-title-2}

Former general practitioner Bristol ( b Bristol 1938; q Cambridge/Guy's 1963), died of carcinoma of the prostate on 23 February 1998. Four generations of Bernards practised in Bristol and between them served as medical officer to Colston School continuously from 1871. Richard had an inquisitive mind and wide ranging interests that included sport, history, and above all people. He remained wary of modern information technology, but had an encyclopaedic knowledge of his patients and could recall details of their extended families' history with little prompting. His involvement in medical politics included many years' service on the local medical committee and the Frenchay Health Authority, of which he became vice chairman. In his youth he played rugby for Cambridge and Guy's, and as a great great nephew of W G Grace excelled at cricket, playing as a forceful batsman and medium pace bowler not only for his school but also for Gloucestershire both before and after Cambridge, where he was awarded a blue in each of his three years. He leaves a wife, Dinah, and three daughters.

# John David Creer {#article-title-3}

General practitioner Wirral 1972-97 ( b Crosby 1947; q …
Horizontal gene transfer is not a hallmark of the human genome
Authors: Steven L. Salzberg
Journal: Genome biology (2017)

Crisp et al. recently reported that 145 human genes have been horizontally transferred from distant species. Here, I re-analyze those genes listed by Crisp et al. as having the highest certainty of having been horizontally transferred, as well as 17 further genes from the 2001 human genome article, and find little or no evidence to support claims of horizontal gene transfer (HGT). Please see related Research article: https://genomebiology.biomedcentral.com/articles/10.1186/s13059-015-0607-3
Characterization of tumor-associated B cell subsets in head and neck squamous cell carcinoma.
Authors: Sacha Rothschild, Alex Lechner, Hans Anton Schloesser, Martin Thelen, Alexander Shimabukuro-Vornhagen, Dirk Beutner, Michael S von Bergwelt-Baildon
Journal: Journal of Clinical Oncology (2015)

e22108 Background: Recent evidence suggests that B cells can both promote and inhibit the development and progression of tumors. Tumor-inﬁltrating B cells have been described in a large variety of solid tumors including head and neck squamous cell carcinoma (HNSCC) but there has not been a detailed phenotypic characterization of the different B cell subsets in HNSCC. The aim of this study was to characterize the composition of the B cell infiltrates in HNSCC in order to gain further insight into the role of B cells in HNSCC. Methods: In this study we characterized B cell subsets in primary tumors (n = 18), blood (n = 18) and non-cancerous mucosa (n = 7) of 18 previously untreated patients diagnosed with HNSCC. Furthermore, peripheral blood from healthy donors (n = 10) was analyzed. B cell subsets were analyzed by flow cytometry or immunohistochemistry. Results: Tumor-infiltrating B cells can be found in the majority of HNSCC samples. The percentage of B cells within tumors was higher than that in the peripheral blood of HNSCC patients. HNSCC samples contained a significantly higher percentage of activated B cells (CD86 positive), plasma cells (CD38high/CD138high) and regulatory B cells (CD24high/CD38high or TIM-1 positive) compared to healthy controls and non-cancerous mucosa of HNSCC patients as well as in the peripheral blood of HNSCC patients. Conclusions: B cells constitute a significant proportion of the immune infiltrate in HNSCC. The B cell infiltrate of HNSCC is characterized by an accumulation of CD86 positive activated B cells and plasma cells which is suggestive of an antigen recognizing phenotype and a specific effector B-cell response. However, tumors are also infiltrated by a considerable number of regulatory B cells.
Population-Based Assessment of a Biomarker-Based Screening Pathway to Aid Diagnosis of Monogenic Diabetes in Young-Onset Patients
Authors: Beverley M. Shields, Maggie Shepherd, Michelle Hudson, Timothy J. McDonald, Kevin Colclough, Jaime Peters, Bridget Knight, Chris Hyde, Sian Ellard, Ewan R. Pearson, Andrew T. Hattersley
Journal: Diabetes Care (2017)

OBJECTIVE Monogenic diabetes, a young-onset form of diabetes, is often misdiagnosed as type 1 diabetes, resulting in unnecessary treatment with insulin. A screening approach for monogenic diabetes is needed to accurately select suitable patients for expensive diagnostic genetic testing. We used C-peptide and islet autoantibodies, highly sensitive and specific biomarkers for discriminating type 1 from non–type 1 diabetes, in a biomarker screening pathway for monogenic diabetes. RESEARCH DESIGN AND METHODS We studied patients diagnosed at age 30 years or younger, currently younger than 50 years, in two U.K. regions with existing high detection of monogenic diabetes. The biomarker screening pathway comprised three stages: 1) assessment of endogenous insulin secretion using urinary C-peptide/creatinine ratio (UCPCR); 2) if UCPCR was ≥0.2 nmol/mmol, measurement of GAD and IA2 islet autoantibodies; and 3) if negative for both autoantibodies, molecular genetic diagnostic testing for 35 monogenic diabetes subtypes. RESULTS A total of 1,407 patients participated (1,365 with no known genetic cause, 34 with monogenic diabetes, and 8 with cystic fibrosis–related diabetes). A total of 386 out of 1,365 (28%) patients had a UCPCR ≥0.2 nmol/mmol, and 216 out of 386 (56%) were negative for GAD and IA2 and underwent molecular genetic testing. Seventeen new cases of monogenic diabetes were diagnosed (8 common Maturity Onset Diabetes of the Young [Sanger sequencing] and 9 rarer causes [next-generation sequencing]) in addition to the 34 known cases (estimated prevalence of 3.6% [51/1,407] [95% CI 2.7–4.7%]). The positive predictive value was 20%, suggesting a 1-in-5 detection rate for the pathway. The negative predictive value was 99.9%. CONCLUSIONS The biomarker screening pathway for monogenic diabetes is an effective, cheap, and easily implemented approach to systematically screening all young-onset patients. The minimum prevalence of monogenic diabetes is 3.6% of patients diagnosed at age 30 years or younger.
Abstract 226: p21-activated kinase-1 (Pak1) Mediates Exercise-induced Cardiac Remodeling Through Calcineurin Signaling
Authors: Robert T Davis, Jillian N Simon, Yunbo Ke, Beata M Wolska, R. John Solaro
Journal: Circulation Research (2015)

Aims: Despite its known cardiovascular benefits, the intracellular signaling mechanisms underlying physiological cardiac growth remain poorly understood. Therefore, the purpose of this study was to investigate a novel role of p21-activated-kinase-1 (Pak1) in the regulation of exercise-induced cardiac hypertrophy. Methods &amp; Results: Wild-type and Pak1 KO mice were subjected to six weeks of treadmill endurance exercise-training (ex-training). Cardiac function was assessed via echocardiography, in situ hemodynamics, and the pCa-force relations in skinned fiber preparations at baseline and at the end of the training regimen. Post-translational modifications to the sarcomeric proteins and expression levels of calcium-regulating proteins were also assessed following ex-training. HW/TL and echocardiography data revealed there was marked hypertrophy following ex-training in the WT mice, which was not evident in the KO mice. Additionally, following ex-training, WT mice demonstrated an increase in cardiac contractility, myofilament calcium sensitivity, phosphorylation of cMyBP-C, cTNT, and TM compared to KO mice. The improvement in contractility with ex-training was accompanied by increased protein levels of SERCA2a and calcineurin along with increased phosphorylation of phospholamban. Conclusions: Our data suggest that Pak1 is essential for adaptive physiological cardiac remodeling and support previous evidence that demonstrate Pak1 signaling is important for cardiac growth and survival.
ASS1 immunohistochemistry identifies unclassified hepatocellular adenoma. Experience of a single French liver center
Authors: A.-A. Raymond, J.F. Blanc, J.-W. Dupuy, B. Le Bail, N. Dugot-Senant, C. Balabaud, P. Bioulac-Sage, F. Saltel
Journal: Journal of Hepatology (2017)
Reply
Authors: Jonathan R. Weir-McCall, Phey Ming Yeap, Carla Papagiorcopulo, Kerrie Fitzgerald, Stephen J. Gandy, Matthew Lambert, Jill J.F. Belch, Ian Cavin, Roberta Littleford, Jennifer A. Macfarlane, Shona Z. Matthew, R. Stephen Nicholas, Allan D. Struthers, Frank Sullivan, Shelley A. Henderson, Richard D. White, J. Graeme Houston
Journal: Journal of the American College of Cardiology (2017)
The RNA-binding protein tristetraprolin schedules apoptosis of pathogen-engaged neutrophils during bacterial infection
Authors: Florian Ebner, Vitaly Sedlyarov, Saren Tasciyan, Masa Ivin, Franz Kratochvill, Nina Gratz, Lukas Kenner, Andreas Villunger, Michael Sixt, Pavel Kovarik
Journal: Journal of Clinical Investigation (2017)

Protective responses against pathogens require a rapid mobilization of resting neutrophils and the timely removal of activated ones. Neutrophils are exceptionally short-lived leukocytes, yet it remains unclear whether the lifespan of pathogen-engaged neutrophils is regulated differently from that in the circulating steady-state pool. Here, we have found that under homeostatic conditions, the mRNA-destabilizing protein tristetraprolin (TTP) regulates apoptosis and the numbers of activated infiltrating murine neutrophils but not neutrophil cellularity. Activated TTP-deficient neutrophils exhibited decreased apoptosis and enhanced accumulation at the infection site. In the context of myeloid-specific deletion of Ttp, the potentiation of neutrophil deployment protected mice against lethal soft tissue infection with Streptococcus pyogenes and prevented bacterial dissemination. Neutrophil transcriptome analysis revealed that decreased apoptosis of TTP-deficient neutrophils was specifically associated with elevated expression of myeloid cell leukemia 1 (Mcl1) but not other antiapoptotic B cell leukemia/lymphoma 2 (Bcl2) family members. Higher Mcl1 expression resulted from stabilization of Mcl1 mRNA in the absence of TTP. The low apoptosis rate of infiltrating TTP-deficient neutrophils was comparable to that of transgenic Mcl1-overexpressing neutrophils. Our study demonstrates that posttranscriptional gene regulation by TTP schedules the termination of the antimicrobial engagement of neutrophils. The balancing role of TTP comes at the cost of an increased risk of bacterial infections.
Clinical research platform into molecular testing, treatment and outcome of non-small cell lung carcinoma Patients (CRISP): A prospective German registry in stage IV NSCLC, AIO-TRK-0315
Authors: F. Griesinger, W. Eberhardt, N. Marschner, M. Jänicke, A. Fleitz, J. Sahlmann, A. Karatas, A. Hipper, M. Sebastian, M. Thomas
Journal: Annals of Oncology (2017)
EphB4/ephrinB2 ephrinB1 Interaction Mediated Chronic Myelogenous Leukemia Mesenchymal Stromal Cells Osteogenic Differentiation in Vitro and In Vivo
Authors: Li Lin, Xu Na, Jiang Zhiwu, Lu Qisi, Zhou Xuan, Lu Ziyuan, Huang Jixian, Li Yuling, He Bolin, Pan Chengyun, Li Peng, Liu Xiaoli
Journal: Blood (2016)