tbuckley/cabot-search huggingface dataset:
CT image characteristics of anaplastic lymphoma kinase fusion gene positive (ALK-P) advanced stage non-small cell lung cancer (NSCLC).
Authors: Takuya Oyakawa, Toshiaki Takahashi, Hisao Imai, Hiroaki Akamatsu, Akira Ono, Tetsuhiko Taira, Hirotsugu Kenmotsu, Tateaki Naito, Haruyasu Murakami, Masahiro Endo, Nobuyuki Yamamoto
Journal: Journal of Clinical Oncology (2013)

e19074 Background: Although several clinical and pathological characteristics of ALK-P NSCLC have been reported, to our knowledge, only one report regarding CT findings of resected early stage ALK-P NSCLC have been published (Fukui T et al. Lung Cancer 2012). They concluded resected ALK-P tumors exhibited a solid pattern without ground glass opacities (GGO). However, there is no report regarding CT image characteristics of advanced stage ALK-P NSCLC. Methods: We retrospectively reviewed CT image findings of 20 patients with advanced ALK-P NSCLC and 32 patients with ALK-negative (ALK-N) NSCLC between November 2010 and January 2013 at Shizuoka Cancer Center in Japan. Primary lesion (PL) was classified into three types: GGO (Type G), focal GGO with solid central components (Type GS), solid nodules without GGO (Type S). Results: Characteristics of patients with ALK-P (N=20)/ ALK-N (N=32) were: 7 /17 males and 13/15 females, median age ;51/63 years, non-smokers 13/8 and smokers 7/24, adenocarcinoma;19/32, stage III; 2 /9, stage IV;18/23. None of PL of both ALK-P and ALK-N showed type G. PL of ALK-P (type GS/S;13/7) had a significant high frequency of type GS than that of ALK-N (type GS/S;8/24) (p=0.004). Lymph node metastases were observed in 16 of 20 ALK-P cases, and 26 of 32 ALK-N. The frequency of fusions of metastatic lymph nodes in ALK-P cases (75%) was significantly higher than that in ALK-N cases (31%) (p=0.010). And the frequency of increased concentration of mediastinal fat tissues around metastatic lymph nodes in ALK-P cases (50%) was also significantly higher than that in ALK-N cases (12%) (p=0.011). Intrapulmonary metastases on the initial CT were observed more frequently in ALK-P (12 of 20 cases) than in ALK-N (6 of 32 cases) (p=0.013). There were no specific features regarding liver, bone and brain metastases in ALK-P cases. Conclusions: Advanced stage ALK-P NSCLC has several CT image characteristics. These findings may reflect biological features of ALK-P NSCLC, and can help clinicians suspect their NSCLC patients of having ALK rearrangement.
Comparison of Reduced-Intensity Conditioning with Fludarabine/Busulfan and Fludarabine/Melphalan in Patients 50 Years or Older
Authors: Koji Kawamura, Shinichi Kako, Shuichi Mizuta, Ken Ishiyama, Jun Aoki, Shingo Yano, Takahiro Fukuda, Naoyuki Uchida, Yukiyasu Ozawa, Tetsuya Eto, Koji Iwato, Tatsuo Ichinohe, Yoshiko Atsuta, Yoshinobu Kanda
Journal: Blood (2016)
Computed tomographic findings in subjects who died from respiratory disease in the National Lung Screening Trial
Authors: Esther Pompe, Pim A. de Jong, David A. Lynch, Nikolas Lessmann, Ivana Išgum, Bram van Ginneken, Jan-Willem J. Lammers, Firdaus A.A. Mohamed Hoesein
Journal: European Respiratory Journal (2017)

We evaluated the prevalence of significant lung abnormalities on computed tomography (CT) in patients who died from a respiratory illness other than lung cancer in the National Lung Screening Trial (NLST).In this retrospective case-control study, NLST participants in the CT arm who died of respiratory illness other than lung cancer were matched for age, sex, pack-years and smoking status to a surviving control. A chest radiologist and a radiology resident blinded to the outcome independently scored baseline CT scans visually and qualitatively for the presence of emphysema, airway wall thickening and fibrotic lung disease. The prevalence of CT abnormalities was compared between cases and controls by using chi-squared tests.In total, 167 participants died from a respiratory cause other than lung cancer. The prevalence of severe emphysema, airway wall thickening and fibrotic lung disease were 28.7% versus 4.8%, 26.9% versus 13.2% and 18.6% versus 0.5% in cases and controls, respectively. Radiological findings were significantly more prevalent in deaths compared with controls (all p<0.001).CT-diagnosed severe emphysema, airway wall thickening and fibrosis were much more common in NLST participants who died from respiratory disease, and CT may provide an additional means of identifying these diseases.
Gefitinib or Erlotinib vs Chemotherapy for EGFR Mutation-Positive Lung Cancer: Individual Patient Data Meta-Analysis of Overall Survival
Authors: Chee Khoon Lee, Lucy Davies, Yi-Long Wu, Tetsuya Mitsudomi, Akira Inoue, Rafael Rosell, Caicun Zhou, Kazuhiko Nakagawa, Sumitra Thongprasert, Masahiro Fukuoka, Sally Lord, Ian Marschner, Yu-Kang Tu, Richard J Gralla, Val Gebski, Tony Mok, James Chih-Hsin Yang
Journal: JNCI Journal of the National Cancer Institute (2016)

We performed an individual patient data meta-analysis to examine the impact of first-generation epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor (TKI) therapy on overall survival (OS) in advanced non-small cell lung cancer (NSCLC).Data from trials comparing EGFR-TKI against chemotherapy in exon 19 deletion (del19) or exon 21 L858R (L858R) EGFR mutations patients were used. We performed Cox regression to obtain hazard ratios (HRs) and 95% confidence intervals (CIs). Impact of postprogression therapies was examined in exploratory analyses. All statistical tests were two-sided.Six eligible trials (gefitinib = 3, erlotinib = 3) included 1231 patients; 632 received EGFR-TKI and 599 received chemotherapy. At a median 35.0 months follow-up, there were 780 deaths and 1004 progressions. There was no difference in OS between EGFR-TKI and chemotherapy (HR = 1.01, 95% CI = 0.88 to 1.17, P = .84). There was also no difference in OS for Del19 (n = 682, HR = 0.96, 95% CI = 0.79 to 1.16, P = .68) and L858R (n = 540, HR = 1.06, 95% CI = 0.86 to 1.32, P = .59) subgroups ( P interaction = .47), or according to smoking status, sex, performance status, age, ethnicity, or histology. However, EGFR-TKI statistically significantly prolonged progression-free survival (PFS) overall (HR = 0.37, 95% CI = 0.32 to 0.42, P < .001) and in all subgroups. Following progression, 73.8% from the chemotherapy arm received EGFR-TKI, and 65.9% from the EGFR-TKI arm received chemotherapy. Nine percent from the EGFR-TKI arm received no further treatment vs 0.6% from the chemotherapy arm. Following disease progression, patients randomly assigned to EGFR-TKI had shorter OS than those randomly assigned to chemotherapy (12.8 months, 95% CI = 11.4 to 14.3, vs 19.8 months, 95% CI = 17.6 to 21.7).Despite statistically significant PFS benefit, there is no relative OS advantage with frontline gefitinib or erlotinib vs chemotherapy in EGFR -mutated NSCLC. This finding is likely due to the high rate of crossover at progression.
Diagnostic accuracy of 2-hydroxyglutarate magnetic resonance spectroscopy in newly diagnosed brain mass and suspected recurrent gliomas
Authors: Min Zhou, Yue Zhou, Huijun Liao, Benjamin C Rowland, Xiangquan Kong, Nils D Arvold, David A Reardon, Patrick Y Wen, Alexander P Lin, Raymond Y Huang
Journal: Neuro-Oncology (2018)

Isocitrate dehydrogenase (IDH) mutations result in abnormal accumulation of 2-hydroxyglutarate (2HG) in gliomas that can be detected by MRS. We examined the diagnostic accuracy of 2HG single-voxel spectroscopy (SVS) and chemical shift imaging (CSI) in both newly diagnosed and posttreatment settings. Long echo time (97 ms) SVS and CSI were acquired in 85 subjects, including a discovery cohort of 39 patients who had postoperative residual or recurrent glioma with confirmed IDH-mutation status and 6 normal volunteers, a prospective preoperative validation cohort of 24 patients with newly diagnosed brain mass, and a prospective recurrent-lesion validation cohort of 16 previously treated IDH-mutant glioma patients with suspected tumor recurrence. The optimal thresholds for both methods in diagnosing IDH status were determined by receiver operating characteristic analysis in the discovery cohort and then applied to the 2 validation cohorts to assess the diagnostic performance. The optimal 2HG/creatine thresholds of SVS and 75th percentile CSI for IDH mutations were 0.11 and 0.23, respectively. When applied to the validation sets, the sensitivity, specificity, and accuracy in distinguishing IDH-mutant gliomas in the preoperative cohort were 85.71%, 100.00%, and 94.12% for SVS, and 100.00%, 69.23%, and 81.82% for CSI, respectively. In the recurrent-lesion cohort, the sensitivity, specificity, and accuracy for discriminating IDH-positive recurrent gliomas were 40.00%, 62.50%, and 53.85% for SVS, and 66.67%, 100.00%, and 86.67% for CSI, respectively. 2HG MRS provides diagnostic utility for IDH-mutant gliomas both preoperatively and at time of suspected tumor recurrence. SVS has a better diagnostic performance for untreated IDH-mutant gliomas, whereas CSI demonstrates greater performance in identifying recurrent tumors.
Autoimmune‐like chronic hepatitis induced by olmesartan
Authors: Sandrine Barge, Marianne Ziol, Jean‐Charles Nault
Journal: Hepatology (2017)

1Liver UnitJean Verdier Hospital, Paris Seine Saint Denis HospitalBondyFrance 2UMR 1162Functional Genomic of Solid Tumors, INSERMParisFrance 3Unité de Formation et de Recherche Santé Médecine et Biologie humaineUniversité Paris 13, Communauté d'Universités et Etablissements Sorbonne Paris CitéParisFrance *ADDRESS CORRESPONDENCE AND REPRINT REQUESTS TO:Jean‐Charles Nault, M.D., Ph.D.APHP, Hôpitaux universitaires Paris–Seine Saint‐Denis, Site Jean Verdier, Pôle d'Activité Cancérologique spécialisée, Service d'HépatologieAvenue du 14 juillet 93140 BondyFranceE‐mail: [email protected]Tel: +01 53 72 51 94
Histopathological and Immunological Characteristics of Tachycardia-Induced Cardiomyopathy
Authors: Karin A.L. Mueller, David Heinzmann, Karin Klingel, Petra Fallier-Becker, Reinhard Kandolf, Antonios Kilias, Britta Walker-Allgaier, Oliver Borst, Jörg Kumbrink, Thomas Kirchner, Harald Langer, Tobias Geisler, Jürgen Schreieck, Michael Gramlich, Meinrad Gawaz, Peter Seizer
Journal: Journal of the American College of Cardiology (2017)
Abstract P040: Mst1 Physically Interacts with and Phosphorylates Beclin1, Thereby Negatively Regulating Autophagy in the Heart
Authors: Yasuhiro Maejima, Shiori Kyoi, Peiyong Zhai, Junichi Sadoshima
Journal: Circulation Research (2011)

Autophagy mediates protein degradation and participates in protein quality control (QC). Inhibition of autophagy below physiological levels induces protein aggregation and cellular dysfunction. Beclin1 is a BH3-only protein that binds to Bcl-2. Bcl-2 negatively regulates autophagy through interaction with Beclin1. Here we show that the interaction between Bcl-2 and Beclin1 is regulated by mammalian STE 20 like-kinase-1 (Mst1), a proapoptotic kinase, in the heart. In Mst1 transgenic mice (Tg-Mst1), a model of dilated cardiomyopathy, accumulation of aggresomes was significantly increased and p62/SQSTM1, a protein degraded by autophagy, accumulated markedly in the myocardium. Autophagosome formation, as evaluated by GFP-LC3 dots, was suppressed in Tg-Mst1. The activity of Mst1 was suppressed by amino acid deprivation (AD) in cultured cardiomyocytes (CMs), and restoration of Mst1 activity attenuated AD-induced autophagy, as evaluated by LC3-II/ LC3-I and accumulation of p62/SQSTM1. Mst1 inhibited the kinase activity of the Beclin1-Vps34 (Class III PI3K) complex in CMs. ABT-737, a BH3 mimetic compound, reversed the Mst1-induced suppression of autophagy. Mst1-induced suppression of autophagy was alleviated when Bcl-2 were downregulated in CMs. Mst1 physically interacts with Beclin1 and stimulation of Mst1 enhances the interaction between Beclin1 and Bcl-2 in CMs. In vitro kinase assays using recombinant Beclin1 as substrate showed that Mst1 phosphorylates Beclin1. Using mass spectroscopy, we found that Mst1 phosphorylates Beclin1 at Thr 108 that located in its BH3 domain. Transduction of the Beclin1 Thr108Asp mutant adenovirus (Ad-T108D) attenuated AD-induced autophagy in CMs, and injection of Beclin1 Thr108Ala mutant adenovirus (Ad-T108A), but not Ad-T108D, restored starvation-induced LV dysfunction (LVEF: Ad-LacZ=0.51±0.05, Ad-T108D=0.53±0.04, Ad-T108A=.66±0.05, p&lt;0.05) in beclin1 −/+ mice. Collectively, these results suggest that Mst1 inhibits autophagy through phosphorylation of Beclin1, enhancement of Beclin1-Bcl-2 interaction, and suppression of Vps34. Activation of Mst1 by stress suppresses autophagy below physiological levels and inhibits protein QC, which in turn may contribute to cardiac dysfunction.
P08.38 A 3D-Engineered Conformal Implant Releases DNA Nanocomplexs for Eradicating the Post-Surgery Residual Glioblastoma
Authors: Q. Mao, Y. Yang
Journal: Neuro-Oncology (2017)

Gene therapy has great promise for glioblastoma treatment; however, it remains a great challenge to efficiently deliver genes to the brain. The incomplete resection of glioblastoma always leads to poor prognosis. Here, we design a 3 3D-engineered conformal implant for eradicating the post-surgery residual glioblastoma. This implant is constructed by 3D-printing technology to match the tumor cavity and release an oncolytic virus-inspired DNA nanocomplex to kill glioblastoma cells through apoptosis induction. Meanwhile, a 3D-engneered subcutaneous glioblastoma xenograft is built to mimic the resection tumor cavity in mice. Insertion of the implant into the glioblastoma resection cavity efficiently delays tumor recurrence and significantly prolongs overall survival. This study provides a proof-of-concept of glioblastoma therapy using a conformal implant that releases oncolytic DNA nanocomplexs. This strategy could lead to the development of future precision therapy for eradicating post-surgery residual tumors.
Functional screen of MSI2 interactors identifies an essential role for SYNCRIP in myeloid leukemia stem cells
Authors: Ly P Vu, Camila Prieto, Elianna M Amin, Sagar Chhangawala, Andrei Krivtsov, M Nieves Calvo-Vidal, Timothy Chou, Arthur Chow, Gerard Minuesa, Sun Mi Park, Trevor S Barlowe, James Taggart, Patrick Tivnan, Raquel P Deering, Lisa P Chu, Jeong-Ah Kwon, Cem Meydan, Javier Perales-Paton, Arora Arshi, Mithat Gönen, Christopher Famulare, Minal Patel, Elisabeth Paietta, Martin S Tallman, Yuheng Lu, Jacob Glass, Francine E Garret-Bakelman, Ari Melnick, Ross Levine, Fatima Al-Shahrour, Marcus Järås, Nir Hacohen, Alexia Hwang, Ralph Garippa, Christopher J Lengner, Scott A Armstrong, Leandro Cerchietti, Glenn S Cowley, David Root, John Doench, Christina Leslie, Benjamin L Ebert, Michael G Kharas
Journal: Nature Genetics (2017)
Through translational prospective study, the GSTP1 Ile105Val polymorphism emerges as prognostic marker in de novo large B-cell lymphoma patients
Authors: M T Delamain, E C M Miranda, G J Lourenço, C A de Souza, C S P Lima
Journal: Blood Cancer Journal (2017)

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of non-Hodgkin lymphoma (NHL), and its current standard of care is chemoimmunotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). Clinic-pathological markers such as the International Prognostic Index in rituximab era (R-IPI) and β2-microglobulin serum level (B2M) have been used as prognostic factors in DLBCL,1, 2 but do not predict patients’ outcome in several cases.
Concern regarding the alleged spread of hypervirulent lymphogranuloma venereum Chlamydia trachomatis strain in Europe
Authors: Helena MB Seth-Smith, Juan C Galán, Daniel Goldenberger, David A Lewis, Olivia Peuchant, Cecile Bébéar, Bertille de Barbeyrac, Angele Bénard, Ian Carter, Jen Kok, Sylvia M Bruisten, Bart Versteeg, Servaas A Morré, Nicholas R Thomson, Adrian Egli, Henry JC de Vries
Journal: Eurosurveillance (2017)

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OS01.2 Human glioblastoma arises from normal subventricular zone harboring tumor-initiating mutations
Authors: J. Lee, J. Lee, J. Park, S. Yoon, J. Lee, S. Kim, J. Moon, J. Chang, S. Kang, J. Lee
Journal: Neuro-Oncology (2017)

Introduction: Glioblastoma (GBM) is the most devastating and incurable brain tumor. Although the identification of cells with tumor ­initiating mutations or their location can provide the fundamental basis for understanding disease progression, the origin of GBM remains controversial due to the lack of direct evidence in human GBM patients. Materials and Methods: Here, we performed ultra-deep sequencing of triple-matched tissues of i) radiologically and pathologically normal subventricular zone (SVZ), which is distant from tumor, ii) GBM tumor, and iii) blood (or normal cortical tissues) from patients with GBM (IDH-wildtype), compared to those with other type of brain tumors such as GBM (IDH-mutant), meningioma, oligodendrgolioma, metastatic brain tumor, and GBM (IDH-wildtype) with SVZ-invasion. Results: Surprisingly, we found that in 60% of GBM, IDH-wildtype patients (6 of 10), normal appearing and distant SVZ already contained the low level of GBM mutations such as TP53, PTEN, EGFR, PDGRF or TERT variations observed in the matched tumor. Single cell sequencing of GBM tumors and laser capture microdissection analysis of the SVZ show that mutations are enriched in GFAP-positive cells of the astrocyte ribbon area, which clonally evolved from the SVZ to the distant GBM tumor. Furthermore, using CRISPR-Cas9 system in the postnatal mouse brain, we showed that neural stem cells with TP53, PTEN, EGFR mutations migrated away from the mutated SVZ site and then formed the malignant glioma in the distant cortical region. Conclusions: Taken together, this study provides the direct evidence that human glioblastoma arises from the distant SVZ that is normal-appearing but harboring tumor-initiating mutations.
Ambient particulate matter and COPD in China: a challenge for respiratory health research
Authors: Anke Hüls, Tamara Schikowski
Journal: Thorax (2017)

Worldwide, COPD is an important cause of morbidity and mortality. The condition is increasing in prevalence, it is a major public health problem and it will remain a challenge for clinicians within the 21st century.1 COPD has become the third leading cause of death,2 resulting in 2.9 million deaths globally in 2013.3 The Global Burden of Diseases Study estimated that around 1.2 million premature deaths and 25 million disability-adjusted life-years annually in China alone could be attributed to air pollution.3 In recent years, evidence is growing that the exposure to ambient air pollution may contribute to the growing global burden of COPD.4 In many Western countries, levels of ambient air pollution have been improved with the setting of upper limits and better urban planning. However, air pollution in low/middle-income countries with rapid industrialisation, such as China, has become a major global problem.5 Severe air pollution events, with levels of fine particulate matter (PM) exceeding 690 μg/m3,6 result in a health burden that has increased …
Possible role of pandemic AH1N1 swine flu virus in a childhood leukemia cluster
Authors: G Cazzaniga, L Bisanti, G Randi, S Deandrea, S Bungaro, F Pregliasco, D Perotti, F Spreafico, G Masera, M G Valsecchi, A Biondi, M Greaves
Journal: Leukemia (2017)

The causation of acute lymphoblastic leukemia (ALL), the main subtype of childhood cancer, is still unresolved and the difficulty in uncovering a likely multi-factorial etiological pathway is compounded by biological heterogeneity of what is a relatively rare disease.1, 2
P03.11 Diffuse grade II/III astrocytomas revisited by integration of molecular markers as per WHO 2016 classification- A study of 180 cases
Authors: K. Kumari, A. Kumar
Journal: Neuro-Oncology (2017)

The updated WHO 2016 classification of CNS tumors combines histological and molecular features for an integrated classification. We aimed to redefine grade II/III diffuse astrocytomas earlier diagnosed as per WHO 2007 using molecular markers: IDH1/2 mutation, 1p/19q co-deletion, EGFR amplification as per new 2016 WHO classification guidelines. A total of 180 grade II (n=94) and grade III (n=86) astrocytic tumors were included diagnosed from 2014 to 2016. H&E slides were reviewed by three neuropathologists. An algorithm-based stepwise analysis was undertaken. Immunohistochemistry for IDH1-R132H and ATRX was done first. IDH1 negative cases were subjected to Sanger sequencing for IDH1/2 mutation. Cases with loss of ATRX and with IDH mutation by IHC/sequencing were categorized as astrocytomas IDH mutant. ATRX retained cases were analysed for 1p/19q deletion by FISH. All IDH wild-type tumors, and IDH mutant tumors with no ATRX loss or 1p/19q co-deletion were subjected to FISH to look for EGFR amplification. p53 IHC and MIB-1 were done in all cases. A cut-off of 50% or more of nuclei showing strong immunostaining was taken as p53 positive. Of the cases diagnosed as astrocytoma grade II/III by morphological criteria, 57% had the molecular fingerprint of astrocytoma (IDH+/ATRX loss). Molecular profile of oligodendroglioma (IDH mutant/ATRX retained/1p/19q co-deleted) was noted in 1% of cases while 1% were primary glioblastomas (IDH wild-type/ EGFR amplified). p53 expression varied in these groups, being 78% in the first and nil in the latter two. The remaining 41% included 23% IDH wild-type, EGFR non-amplified and 18% IDH mutant but with retained ATRX and no 1p/19q co-deletion which did not match the expected molecular profile of astrocytomas, oligodendrogliomas or glioblastomas. These unclassified cases encompass a heterogeneous group which needs further molecular evaluation for accurate classification. Algorithmic approach to molecular characterization of gliomas is important for accurate diagnosis and prognostication. Use of such an approach alters the frequency of astrocytoma, oligodendroglioma and glioblastoma diagnosis as shown by change in diagnosis from astrocytoma to oligodendroglioma and glioblastoma in some of our cases. Reclassification of tumors with histological-genetic discordance is warranted especially for improved patient care and inclusion in clinical trials in order to ensure uniformity of patients subgroups. Current WHO category of both IDH mutant and wild-type astrocytomas encompass a heterogeneous group of tumors, especially the subgroups of astrocytomas that do not have classical molecular fingerprint of astrocytoma/oligodendroglioma/glioblastoma, which need further evaluation to identify novel pathogenetic pathways.