tbuckley/cabot-search huggingface dataset:
Reply to Jain <i>et al.</i>: Improving Lung Function in Severe Heterogenous Emphysema with the Spiration Valve System: Still a Great Need to “EMPROVE”
Authors: Gerard J. Criner
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

To the Editor:We read with keen interest the results of a randomized controlled trial of the Spiration Valve System in patients with severe emphysema by Criner and colleagues (1).We congratulate the authors for presenting a well-designed study on an important clinical question.It has been previously reported that use of endobronchial valves in severe emphysema leads to improvement in FEV 1 compared with placebo, similar to the results found in the present study (2).However, some important points regarding the reported results need careful consideration and further discussion.Although the authors report significant improvement in FEV 1 compared with baseline on 6-month follow-up in the valve group, the overall responder rate is only 37%; that is, only approximately one-third of all patients who received the valve actually demonstrated benefit in airflow.Similarly, although the patient-centered outcomes (i.e., dyspnea and quality of life) improved in the valve group, they did so in only 53% and 54% of subjects, respectively, at 6 months.We feel that this response rate is extremely low by any standard, especially considering the high cost and potential complications associated with valve placement.Therefore, it would be desirable to interpret these results in the proper perspective, based on cost benefit.Considering the patient population in which endobronchial valve therapy is being considered (i.e., those with severe airflow limitation, limited exercise capacity, and receiving long-term oxygen therapy), it may be worthwhile to identify predictors of nonresponse in the endobronchial valve therapy group in an attempt to identify patients most likely to derive benefit from this intervention.This may have important implications for rationalizing clinical practice of emphysema management.
A longitudinal assessment of retinal function and structure in the APP/PS1 transgenic mouse model of Alzheimer’s disease
Authors: Dana Georgevsky, Stephanie Retsas, Newsha Raoufi, Olga Shimoni, S. Mojtaba Golzan
Journal: Translational Neurodegeneration (2019)

Abstract Background A great body of evidence suggests that there are retinal functional and structural changes that occur in Alzheimer’s disease (AD). However, whether such changes are primary or secondary remains to be elucidated. We studied a range of retinal functional and structural parameters in association with AD- specific pathophysiological markers in the double transgenic APP/PS1 and control mice across age. Methods Electroretinogram (ERG) and optical coherence tomography (OCT) was performed in APP/PS1 and wild type (WT) control mice every 3 months from 3 to 12 months of age. For functional assessment, the a- and b-wave of the ERG, amplitude of oscillatory potentials (OP) and the positive scotopic threshold response (pSTR) were quantified at each time point. For structural assessment, the inner and outer retinal thickness was segmented and measured from OCT scans. Episodic memory was evaluated at 6, 9 and 12 months of age using the novel object recognition test. Amyloid beta (Aβ) distribution in the hippocampus and the retina were visualised at 3, 6 and 12 months of age. Inter- and intra- group analysis was performed to study rate of change for each parameter between the two groups. Results Inter-group analysis revealed a significant difference in b-wave and OPs of APP/PS1 compared to WT controls starting from 3 months ( p &lt; 0.001). There was also a significant difference in the amplitude of pSTR between the two groups starting from 6 months ( p &lt; 0.001). Furthermore, a significant difference in the inner retinal thickness, between the two groups, was observed starting from 9 months ( p &lt; 0.001). Conclusions We observed an age-related decline in retinal functional and structural parameters in both APP/PS1 and WT controls, however, inter-group analysis revealed that inner retinal functional and structural decline is exacerbated in APP/PS1 mice, and that retinal functional changes precede structural changes in this strain. Further studies are required to confirm whether such phenomenon occurs in humans and if studying retinal functional changes can aid-in early assessment of AD.
Activity of the novel Aurora kinase B inhibitor AZD2811 in biomarker-defined models of small cell lung cancer
Authors: C.M. Della Corte, L. Ajpacaja, R.J. Cardnell, C.M. Gay, Q. Wang, L. Shen, K. Ramkumar, A.C. Stewart, Y.-H. Fan, C.A. Adelman, J. Travers, J. Wang, J. Heymach, L.A. Byers
Journal: Annals of Oncology (2019)
Thioredoxin-1 maintains mitochondrial function via mechanistic target of rapamycin signalling in the heart
Authors: Shin-Ichi Oka, Adave Chin, Ji Yeon Park, Shohei Ikeda, Wataru Mizushima, Guersom Ralda, Peiyong Zhai, Mingming Tong, Jaemin Byun, Fan Tang, Yudai Einaga, Chun-Yang Huang, Toshihide Kashihara, Mengyuan Zhao, Jihoon Nah, Bin Tian, Yoko Hirabayashi, Junji Yodoi, Junichi Sadoshima
Journal: Cardiovascular Research (2019)

Abstract Aims Thioredoxin 1 (Trx1) is an evolutionarily conserved oxidoreductase that cleaves disulphide bonds in oxidized substrate proteins such as mechanistic target of rapamycin (mTOR) and maintains nuclear-encoded mitochondrial gene expression. The cardioprotective effect of Trx1 has been demonstrated via cardiac-specific overexpression of Trx1 and dominant negative Trx1. However, the pathophysiological role of endogenous Trx1 has not been defined with a loss-of-function model. To address this, we have generated cardiac-specific Trx1 knockout (Trx1cKO) mice. Methods and results Trx1cKO mice were viable but died with a median survival age of 25.5 days. They developed heart failure, evidenced by contractile dysfunction, hypertrophy, and increased fibrosis and apoptotic cell death. Multiple markers consistently indicated increased oxidative stress and RNA-sequencing revealed downregulation of genes involved in energy production in Trx1cKO mice. Mitochondrial morphological abnormality was evident in these mice. Although heterozygous Trx1cKO mice did not show any significant baseline phenotype, pressure-overload-induced cardiac dysfunction, and downregulation of metabolic genes were exacerbated in these mice. mTOR was more oxidized and phosphorylation of mTOR substrates such as S6K and 4EBP1 was impaired in Trx1cKO mice. In cultured cardiomyocytes, Trx1 knockdown inhibited mitochondrial respiration and metabolic gene promoter activity, suggesting that Trx1 maintains mitochondrial function in a cell autonomous manner. Importantly, mTOR-C1483F, an oxidation-resistant mutation, prevented Trx1 knockdown-induced mTOR oxidation and inhibition and attenuated suppression of metabolic gene promoter activity. Conclusion Endogenous Trx1 is essential for maintaining cardiac function and metabolism, partly through mTOR regulation via Cys1483.
IFCT-1701 DICIPLE: A randomized phase III trial comparing continuation nivolumab-Ipilimumab doublet immunotherapy until progression versus observation in patients with PDL1-positive stage IV non-small cell lung cancer (NSCLC) after nivolumab-ipilimumab induction treatment
Authors: G. Zalcman, A.C. Toffart, A.-C. Madroszyk Flandin, O. Molinier, C. Dayen, T. Egenod, A. Dixmier, E. Giroux Leprieur, P. Masson, N. Cloarec, L. Thibonnier, L. Favier, D. Debieuvre, J. Mazieres, S. Van Hulst, E. Pichon, E. Amour, F. Morin, P.-J. Souquet
Journal: Annals of Oncology (2019)
Abstract 3667: Comparison of Risk Profiles between Survivors and Victims of Sudden Cardiac Death of an Acute Coronary Event
Authors: Kari S Kaikkonen, Marja-Leena Kortelainen, Heikki V Huikuri
Journal: Circulation (2007)

Introduction. There is little information on the specific risk factors leading to sudden cardiac death (SCD) during an acute coronary event, because the risk variables may overlap with those of non-fatal coronary event. This study was designed to compare the risk profiles of SCD victims and survivors of an acute coronary event. Methods and Results. A case-control study included consecutive victims of SCD (n=425, mean age 64±11 years) verified to be due to an acute coronary event at medicolegal autopsy and consecutive patients surviving an acute myocardial infarction (AMI, n=644, mean age 62±10 years). Common cardiovascular risk factors, cardiac hypertrophy, and severity of coronary artery disease (CAD) were assessed in both groups. Family history of SCD (odds ratio 1.5, 95% CI 1.0 to 2.2, p=0.03), male gender (odds ratio 1.8, 95% CI 1.3 to 2.4, p&lt;0.001), current smoking (odds ratio 2.0, 95% CI 1.5 to 2.6, p&lt;0.001), cardiac hypertrophy (odds ratio 3.0, 95% CI 2.3 to 3.9, p&lt;0.001) and 3-vessel CAD (odds ratio 5.4, 95% CI 3.6 to 8.2, p&lt;0.001) were more common among the victims of SCD as compared to survivors of AMI. On the contrary, history of hypercholesterolemia (p&lt;0.001) was less common among the SCD victims. There was a cumulative increase of risk of being a SCD victim vs. AMI survivor when more than one risk factor was present, the odds ratio being 44.3 (95% CI 8.0 to 246.7) in a current male smoker with a family history of SCD and cardiac hypertrophy. When 3-vessel CAD was added to the combined risk score, all subjects (7% of the SCD victims) were in the group of SCD giving a 100% sensitivity and specificity, respectively, in differentiating between the SCD victims and AMI survivors. Conclusions. There are specific features that differentiate the victims of SCD from survivors of an acute coronary event. Clustering of several variables, such as family history of SCD, smoking, cardiac hypertrophy, and 3-vessel CAD indicate a very high risk of SCD.
Up-Regulation of CAR-T Cells after G-CSF and Dexamethasone Treatment in a Defuse Large B Cell Lymphoma Patient Receiving 4SCAR19 T Cell Therapy
Authors: Hongmei Jing, Lung-Ji Chang, Mingyi Chen, Fang Bao, Jing Wang, Wenming Wang, Yuanyuan Liu, Hao-Hsian Kuo, Yuchen Liu, Lujia Dong
Journal: Blood (2015)
Interventional Therapies for Acute Pulmonary Embolism: Current Status and Principles for the Development of Novel Evidence: A Scientific Statement From the American Heart Association
Authors: Jay Giri, Akhilesh K. Sista, Ido Weinberg, Clive Kearon, Dharam J. Kumbhani, Nimesh D. Desai, Gregory Piazza, Mark T. Gladwin, Saurav Chatterjee, Taisei Kobayashi, Christopher Kabrhel, Geoffrey D. Barnes
Journal: Circulation (2019)

Pulmonary embolism (PE) represents the third leading cause of cardiovascular mortality. The technological landscape for management of acute intermediate- and high-risk PE is rapidly evolving. Two interventional devices using pharmacomechanical means to recanalize the pulmonary arteries have recently been cleared by the US Food and Drug Administration for marketing, and several others are in various stages of development. The purpose of this document is to clarify the current state of endovascular interventional therapy for acute PE and to provide considerations for evidence development for new devices that will define which patients with PE would derive the greatest net benefit from their use in various clinical settings. First, definitions and limitations of commonly used risk stratification tools for PE are reviewed. An adjudication of risks and benefits of available interventional therapies for PE follows. Next, considerations for optimal future evidence development in this field are presented in the context of the current US regulatory framework. Finally, the document concludes with a discussion of the pros and cons of the rapidly expanding PE response team model of care delivery.
Endocrine therapy alone versus targeted combination strategy as first line treatment in elderly patients with hormone receptor-positive advanced breast cancer: Meta-analysis of phase II and III randomized clinical trials
Authors: C. Omarini, I. Sperduti, M. Barbolini, C. Isca, A. Bocconi, A. Toss, L. Cortesi, E. Barbieri, F. Piacentini, S. Cascinu, L. Moscetti
Journal: Annals of Oncology (2019)
Erythematotelangiectatic rosacea and subclinical demodicosis
Authors: F. Forton, V. De Maertelaer
Journal: British Journal of Dermatology (2019)

Demodex mites are small parasites that live in the skin pores of all adult humans, mainly on the face, and feed on human cells. Demodicosis is a facial skin condition that occurs when the mites proliferate (multiply) abnormally. Demodicosis shows as scales on the skin surface and, when the mites cause inflammation, by redness and/or red or weeping spots. Rosacea is another frequent skin condition affecting more than 10% of the population and characterised by facial redness. Sometimes spots develop and the condition is then called papulopustular rosacea (PPR). The cause of rosacea is still controversial, but it has been suggested that Demodex mites may be involved, because patients with PPR have a high density of mites on the facial skin, similar to patients with demodicosis. In this study, from Belgium, the density of Demodex mites was measured by two successive skin biopsies in patients in the early stage of a condition called erythematotelangiectatic rosacea (ETR), where patients have only redness without spots. The mean densities were lower than the densities in patients with PPR and patients with demodicosis but higher than in patients with healthy skin and patients with other skin conditions. The authors suggest that ETR may favour Demodex proliferation and may represent an early phase of demodicosis, with mites beginning to proliferate but not yet clinically visible. As such, dermatologists should look for Demodex mites in patients with ETR, so that appropriate treatment can be offered if densities are high.
A parent-of-origin effect of the RB1 mutations in retinoblastoma with low penetrance and variable expressivity
Authors: E.A. Alekseeva, O.V. Babenko, V.M. Kozlova, T.L. Ushakova, T.P. Kazubskaya, S.V. Sahakyan, A.S. Tanas, D.V. Zaletaev, V.V. Strelnikov
Journal: Annals of Oncology (2019)
Effectiveness and safety of nivolumab in the treatment of lung cancer patients in France: Updated survival and subgroup analysis from the real-world EVIDENS study
Authors: F. Barlesi, A. Dixmier, D. Debieuvre, C. Raspaud, J.B. Auliac, N. Benoit, P. Bombaron, D. Moro-Sibilot, C. Audigier-Valette, B. Asselain, P. Lamoureux, F.-E. Cotté, V. Allan, M. Daumont, N. Ozan, C. Calvet, M. Perol
Journal: Annals of Oncology (2019)
Abscopal tumor regression effects of high-dose spatially fractionated GRID radiation
Authors: Marianna Zagurovskaya-Sultanov, Mohammed Mommin Shareef, Seema Gupta, Mohamed M. Mohiuddin, Mansoor M. Ahmed
Journal: Cancer Research (2005)

5704   This study evaluates and compares the tumor regressing effects of low energy high-dose spatially fractionated GRID radiation (SFGRT) with conventional ionizing radiation therapy (IRT) in Human Lung adenocarcinoma cells, A549, model tumor system. Tumors were developed in both right (RT) and left (LT) flanks of the nude mice (86 in number), which were randomly assigned to following treatment regimen: Group I: No treatments for LT and RT; Group II: LT treated with 15 Gy SFGRT as a single dose and RT remained untreated; Group III: LT treated with 15 Gy SFGRT plus five fractions of 2 Gy IRT and RT tumor was left untreated; Group IV: LT treated with 15 Gy SFGRT as a single dose and RT was exposed to five fractions of 2 Gy IRT; Group V: LT was treated with 7.5 Gy IRT as a single and RT was left untreated; Group VI: LT treated with 7.5 Gy IRT plus five fractions of 2 Gy IRT and RT remained untreated; Group VII: LT treated with a single dose 7.5 Gy IRT and RT was exposed to five fractions of 2 Gy IRT. Tumor size was monitored semi-weekly for 90 days. Two mice from each group were euthanized at 3 hours after high-dose and 24 hours after the end of treatment for the tumor tissue harvest. Apoptosis of tumor cells was assessed by TUNEL. Expression kinetics of mRNA and protein for Egr-1, TNF-α, TRAIL, TRAIL receptor, bax, bcl-2, p65, phospho-IkB and cytochrome C release were assessed using real-time quantitative RT-PCR and Western blot / immunoflourescence respectively. Volumetric analysis of tumor size revealed that in Group II the regression of both left and right tumors was less pronounced when compared to Group VI. However, in Group II both left and right tumor showed a very stable and sustained tumor growth delay when compared to Group V. No significant differences in terms of tumor regression and tumor delay (in both RT and LT tumors) was observed between Group III and Group VI. RT and LT tumors in Group IV regressed significantly with a prolonged and sustained tumor growth delay. This effect was not observed in corresponding Group VII where the tumor growth delay was very short. Pro-apoptotic proteins such as Egr-1 and Bax were induced in Group II and IV associated with no changes in Bcl-2 protein expression. Tumor regression was observed in all treated groups when compared to control group I. Increased regression of the untreated RT tumor in the animals in which the LT tumor was exposed to SFGRT suggests that the high-dose SFGRT may released tumoricidal factors such as cytokines (TNF-α or TRAIL) systemically in the mice which may cause an abscopal tumor regression response with increased apoptosis.
Comparable responses of melanoma at primary site and synchronous lymph node metastases upon neoadjuvant ipilimumab (IPI) and nivolumab (NIVO)
Authors: J.M. Versluis, I.L.M. Reijers, E.A. Rozeman, A.C.J. van Akkooi, W.J. van Houdt, C. Bierman, B.A. van de Wiel, G.V. Long, C.U. Blank
Journal: Annals of Oncology (2019)
Weight loss is an underestimated adverse event with cabozantinib in patients with metastastic renal cell carcinoma (mRCC)
Authors: E. Colomba, C. Alves Costa Silva, G. Le Teuff, A. Benchimol-Zouari, A. Guida, L. Derosa, B. Raynard, B. Escudier, L. Albiges
Journal: Annals of Oncology (2019)
S100A10 Is a Critical Mediator of GAS6/AXL–Induced Angiogenesis in Renal Cell Carcinoma
Authors: Yiren Xiao, Hongjuan Zhao, Lei Tian, Rosalie Nolley, Anh N. Diep, Anne Ernst, Katherine C. Fuh, Yu Rebecca Miao, Rie von Eyben, John T. Leppert, James D. Brooks, Donna M. Peehl, Amato J. Giaccia, Erinn B. Rankin
Journal: Cancer Research (2019)

Abstract Angiogenesis is a hallmark of cancer that promotes tumor progression and metastasis. However, antiangiogenic agents have limited efficacy in cancer therapy due to the development of resistance. In clear cell renal cell carcinoma (ccRCC), AXL expression is associated with antiangiogenic resistance and poor survival. Here, we establish a role for GAS6/AXL signaling in promoting the angiogenic potential of ccRCC cells through the regulation of the plasminogen receptor S100A10. Genetic and therapeutic inhibition of AXL signaling in ccRCC tumor xenografts reduced tumor vessel density and growth under the renal capsule. GAS6/AXL signaling activated the expression of S100A10 through SRC to promote plasmin production, endothelial cell invasion, and angiogenesis. Importantly, treatment with the small molecule AXL inhibitor cabozantinib or an ultra-high affinity soluble AXL Fc fusion decoy receptor (sAXL) reduced the growth of a pazopanib-resistant ccRCC patient-derived xenograft. Moreover, the combination of sAXL synergized with pazopanib and axitinib to reduce ccRCC patient-derived xenograft growth and vessel density. These findings highlight a role for AXL/S100A10 signaling in mediating the angiogenic potential of ccRCC cells and support the combination of AXL inhibitors with antiangiogenic agents for advanced ccRCC. Significance: These findings show that angiogenesis in renal cell carcinoma (RCC) is regulated through AXL/S100A10 signaling and support the combination of AXL inhibitors with antiangiogenic agents for the treatment of RCC.
Implications of single nucleotide polymorphisms (SNPs) in androgen related-genes in outcome of metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone (Abi) and enzalutamide (Enza)
Authors: I.M. Aragon, Y. Cendón, D. Lorente, R Lozano Mejorada, N Romero Laorden, A Medina Colmenero, J. Puente, R. Villatoro, S Vazquez Estevez, J.M. Piulats, N. Lainez, E. Fernandez-Parra, A González del Alba, A Hernández Jorge, B. Olmos, L. Rivera, M.I. Pacheco, D Olmos Hidalgo, E. Castro
Journal: Annals of Oncology (2019)
Skeletal muscle loss as an adverse event during cabozantinib treatment in patients with metastatic renal cell carcinoma
Authors: C. Alves Costa Silva, D. Afonso, E. Colomba, G. Le Teuff, L. Derosa, B. Raynard, A. Guida, A. Benchimol-Zouari, B. Escudier, F. Bidault, L. Albiges
Journal: Annals of Oncology (2019)
Abstract 2476: Discovery of an androgen-responsive long noncoding RNA that associates with progression of ERG-overexpressing prostate cancers
Authors: Annika Kohvakka, Anastasia Shcherban, Kati K. Kivinummi, Matti Annala, Alfonso Urbanucci, Matti Nykter, Tapio Visakorpi
Journal: Cancer Research (2018)

Abstract Androgen receptor (AR) signaling pathway has an important role in the growth and development of normal prostate, but also in tumorigenesis and progression of prostate cancer (PC). Although the mechanisms of AR signaling have been widely studied and utilized for treatment in advanced PC, the exact role of AR in development of primary PC is unclear. Former studies have found that AR cistrome is reprogrammed during tumorigenesis to bind novel genomic loci by master regulators, including the ETS family transcription factor ERG. While many AR-induced target genes are known, the effect of AR signaling on regulation of long noncoding RNAs (lncRNAs) is poorly understood, especially in the context of PC progression. Previously, we discovered multiple novel PC-associated transcripts (PCATs) to be aberrantly expressed in PC. Here, we evaluated the expression of 39 Tampere PCATs (TPCATs) in 87 radical prostatectomy specimens using high-throughput real-time PCR, and studied their association with time to PSA progression after prostatectomy. Six TPCATs were significantly associated with time to PSA progression, and four of them also associated with extracapsular extension. In addition, we assessed the expression of TPCATs in the TCGA prostate adenocarcinoma cohort, and found many to be correlated with ERG expression. Moreover, publicly available AR ChIP-seq data from PC tumors indicated that several ERG-associated TPCATs had AR-binding sites on their promoters, some of which overlapped with ERG binding sites. Most notably, we found one progression-associated TPCAT that was regulated by AR in an androgen-sensitive manner according to AR siRNA knockdown and DHT stimulation experiments in vitro. The same TPCAT was also highly associated with overexpression of ERG, and further validated to be a highly PC-specific lncRNA that was abundantly expressed in primary PCs. Taken together, these findings give more insight into the role of AR cistrome in the regulation of lncRNAs in primary PC, and introduce a potential novel prognostic marker to be used in early detection of aggressive PC. Citation Format: Annika Kohvakka, Anastasia Shcherban, Kati K. Kivinummi, Matti Annala, Alfonso Urbanucci, Matti Nykter, Tapio Visakorpi. Discovery of an androgen-responsive long noncoding RNA that associates with progression of ERG-overexpressing prostate cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2476.
Phase Ib/IIa study assessing the safety and efficacy of adding AL3818 (anlotinib) to standard platinum-based chemotherapy in subjects with recurrent or metastatic endometrial, ovarian or cervical carcinoma
Authors: D. Miller, D.S. Miller, E. Cheung, M. Huang, M. Schlumbrecht, A. Garcia, M. Loch, A. Jernigan, Z. Li, M. Chen, J. Chen
Journal: Annals of Oncology (2019)
Screening for Immunosuppressive Genes Responsible for Resistance Towards CAR-T Cell Therapy in Cancer Cells
Authors: Aygul Valiullina, Alexey Petukhov, Regina Sayarova, Margarita Zhuravleva, Sevindzh Kletukhina, Sergey Malanin, Emil Bulatov, Albert Rizvanov
Journal: Blood (2018)