tbuckley/cabot-search huggingface dataset:
Prognostic value of novel immune-related genomic biomarkers identified in head and neck squamous cell carcinoma
Authors: Yao Yao, Zhongyi Yan, Senlin Lian, Liangnian Wei, Chao Zhou, Dongju Feng, Yuan Zhang, Jianrong Yang, Ming Li, Yun Chen
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background The immune response within the tumor microenvironment plays a key role in tumorigenesis and determines the clinical outcomes of head and neck squamous cell carcinoma (HNSCC). However, to date, a paucity of robust, reliable immune-related biomarkers has been identified that are capable of estimating prognosis in HNSCC patients. Methods High-throughput RNA sequencing was performed in tumors and matched adjacent tissues from five HNSCC patients, and the immune signatures expression of 730 immune-related transcripts selected from the nCounter PanCancer Immune Profiling Panel were assessed. Survival analyzes were performed in a training cohort, consisting of 416 HNSCC cases, retrieved from The Cancer Genome Atlas (TCGA) database. A prognostic signature was built, using elastic net-penalized Cox regression and backward, stepwise Cox regression analyzes. The outcomes were validated by an independent cohort of 115 HNSCC patients, using tissue microarrays and immunohistochemistry staining. Cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) was also used to estimate the relative fractions of 22 immune-cell types and their correlations coefficients with prognostic biomarkers. Results Collectively, 248 immune-related genes were differentially expressed in paired tumors and normal tissues using RNA sequencing. After process screening in the training TCGA cohort, four immune-related genes ( PVR, TNFRSF12A , IL21R , and SOCS1 ) were significantly associated with overall survival (OS). Integrating these genes with Path_N stage, a multiplex model was built and suggested better performance in determining 5 years OS (receiver operating characteristic (ROC) analysis, area under the curve (AUC)=0.709) than others. Further protein-based validation was conducted in 115 HNSCC patients. Similarly, high expression of PVR and TNFRSF12A were associated with poor OS (Kaplan-Meier p=0.017 and 0.0032), while high expression of IL21R and SOCS1 indicated favorable OS (Kaplan-Meier p&lt;0.0001 and =0.0018). The integrated model with Path_N stage still demonstrated efficacy in OS evaluation (Kaplan-Meier p&lt;0.0001, ROC AUC=0.893). Besides, the four prognostic genes were significantly correlated with activated CD8 + T cells, CD4 + T cells, follicular helper T cells and regulatory T cells, implying the possible involvement of these genes in the immunoregulation and development of HNSCC. Conclusions The well-established model encompassing both immune-related biomarkers and clinicopathological factor might serve as a promising tool for the prognostic prediction of HNSCC.
Mapping functional humoral correlates of protection against malaria challenge following RTS,S/AS01 vaccination
Authors: Todd J. Suscovich, Jonathan K. Fallon, Jishnu Das, Allison R. Demas, Jonathan Crain, Caitlyn H. Linde, Ashlin Michell, Harini Natarajan, Claudia Arevalo, Thomas Broge, Thomas Linnekin, Viraj Kulkarni, Richard Lu, Matthew D. Slein, Corinne Luedemann, Meghan Marquette, Sandra March, Joshua Weiner, Scott Gregory, Margherita Coccia, Yevel Flores-Garcia, Fidel Zavala, Margaret E. Ackerman, Elke Bergmann-Leitner, Jenny Hendriks, Jerald Sadoff, Sheetij Dutta, Sangeeta N. Bhatia, Douglas A. Lauffenburger, Erik Jongert, Ulrike Wille-Reece, Galit Alter
Journal: Science Translational Medicine (2020)

A combination of two Fc antibody features that leverage innate immune function predicts protection from malaria challenge after RTS,S/AS01 vaccination.
線維芽細胞特異的タンパク1/S100A4陽性細胞は,発がん物質のコラーゲン生成およびカプセル化を通じて癌を予防する | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Zhang Jinhua, Chen Lin, Liu Xiaoman, Kammertoens Thomas, Blankenstein Thomas, Qin Zhihai
Journal: Cancer Research (2013)
Pan-cancer image-based detection of clinically actionable genetic alterations
Authors: Jakob Nikolas Kather, Lara R. Heij, Heike I. Grabsch, Chiara Loeffler, Amelie Echle, Hannah Sophie Muti, Jeremias Krause, Jan M. Niehues, Kai A. J. Sommer, Peter Bankhead, Loes F. S. Kooreman, Jefree J. Schulte, Nicole A. Cipriani, Roman D. Buelow, Peter Boor, Nadina Ortiz-Brüchle, Andrew M. Hanby, Valerie Speirs, Sara Kochanny, Akash Patnaik, Andrew Srisuwananukorn, Hermann Brenner, Michael Hoffmeister, Piet A. van den Brandt, Dirk Jäger, Christian Trautwein, Alexander T. Pearson, Tom Luedde
Journal: Nature Cancer (2020)
Fully automated hybrid approach to predict the<i>IDH</i>mutation status of gliomas via deep learning and radiomics
Authors: Yoon Seong Choi, Sohi Bae, Jong Hee Chang, Seok-Gu Kang, Se Hoon Kim, Jinna Kim, Tyler Hyungtaek Rim, Seung Hong Choi, Rajan Jain, Seung-Koo Lee
Journal: Neuro-Oncology (2020)

Abstract Background Glioma prognosis depends on isocitrate dehydrogenase (IDH) mutation status. We aimed to predict the IDH status of gliomas from preoperative MR images using a fully automated hybrid approach with convolutional neural networks (CNNs) and radiomics. Methods We reviewed 1166 preoperative MR images of gliomas (grades II–IV) from Severance Hospital (n = 856), Seoul National University Hospital (SNUH; n = 107), and The Cancer Imaging Archive (TCIA; n = 203). The Severance set was subdivided into the development (n = 727) and internal test (n = 129) sets. Based on T1 postcontrast, T2, and fluid-attenuated inversion recovery images, a fully automated model was developed that comprised a CNN for tumor segmentation (Model 1) and CNN-based classifier for IDH status prediction (Model 2) that uses a hybrid approach based on 2D tumor images and radiomic features from 3D tumor shape and loci guided by Model 1. The trained model was tested on internal (a subset of the Severance set) and external (SNUH and TCIA) test sets. Results The CNN for tumor segmentation (Model 1) achieved a dice coefficient of 0.86–0.92 across datasets. Our hybrid model achieved accuracies of 93.8%, 87.9%, and 78.8%, with areas under the receiver operating characteristic curves of 0.96, 0.94, and 0.86 and areas under the precision-recall curves of 0.88, 0.82, and 0.81 in the internal test, SNUH, and TCIA sets, respectively. Conclusions Our fully automated hybrid model demonstrated the potential to be a highly reproducible and generalizable tool across different datasets for the noninvasive prediction of the IDH status of gliomas.
Clinical outcomes of prexasertib monotherapy in recurrent<i>BRCA</i>wild-type high-grade serous ovarian cancer involve innate and adaptive immune responses
Authors: Erika J Lampert, Ashley Cimino-Mathews, Joo Sang Lee, Jayakumar Nair, Min-Jung Lee, Akira Yuno, Daniel An, Jane B Trepel, Eytan Ruppin, Jung-Min Lee
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Preclinical data suggest cell cycle checkpoint blockade may induce an immunostimulatory tumor microenvironment. However, it remains elusive whether immunomodulation occurs in the clinical setting. To test this, we used blood and fresh tissue samples collected at baseline and post therapy from a phase II trial of the cell cycle checkpoint 1 inhibitor (CHK1i) prexasertib in recurrent ovarian cancer. Methods Paired blood samples and fresh core biopsies, taken before treatment was started at baseline (cycle 1 day 1 (C1D1)) and post second dose on day 15 of cycle 1 (C1D15), were collected. To evaluate changes in the immune responses after treatment, multiparametric flow cytometry for DNA damage markers and immune cell subsets was performed on paired blood samples. RNA sequencing (RNAseq) of paired core biopsies was also analyzed. Archival tissue immune microenvironment was evaluated with immunohistochemistry. All correlative study statistical analyses used two-sided significance with a cut-off of p=0.05. Results Flow cytometric analysis showed significantly increased γ-H2AX staining after CHK1i treatment, accompanied by increased monocyte populations, suggestive of an activated innate immune response (median 31.6% vs 45.6%, p=0.005). Increased expressions of immunocompetence marker HLA-DR (Human Leukocyte Antigen DR antigen) on monocytes and of TBK1, a marker of STING (stimulator of interferon genes) pathway activation, in biopsies were associated with improved progression-free survival (PFS) (9.25 vs 3.5 months, p=0.019; 9 vs 3 months, p=0.003, respectively). Computational analysis of RNAseq data indicated increased infiltration of tumor niches by naïve B-cells and resting memory T-cells, suggestive of a possibly activated adaptive immune response, and greater T-reg infiltration after treatment correlated with worse PFS (9.25 vs 3.5 months, p=0.007). An immunosuppressive adaptive immune response, perhaps compensatory, was also observed on flow cytometry, including lymphodepletion of total peripheral CD4+ and CD8+T cells after CHK1i and an increase in the proportion of T-regs among these T-cells. Additionally, there was a trend of improved PFS with greater tumor-infiltrating lymphocytes (TILs) in archival tissues (13.7 months &gt;30% TILs vs 5.5 months ≤30% TILs, p=0.05). Conclusion Our study demonstrates that a favorable clinical response in high-grade serous ovarian carcinoma patients treated with CHK1i is possibly associated with enhanced innate and adaptive immunity, requiring further mechanistic studies. It is supportive of current efforts for a clinical development strategy for therapeutic combinations with immunotherapy in ovarian cancer.
Ratios of T-cell immune-effectors with tumour associated macrophages and PD-1/PD-L1 axis immune-checkpoint molecules, add to the predictive power of conventional prognosticators in diffuse large B cell lymphoma
Authors: C Keane, F Vari, M Hertzberg, K Le Cao, Green, E Han, JF Seymour, RJ Hicks, D Gill, P Crooks, C Gould, K Jones, LR Griffiths, D Talaulikar, S Jain, J Tobin, MK Gandhi
Journal: The Lancet Haematology (2015)
Second cancer incidence in CLL patients receiving BTK inhibitors
Authors: David A. Bond, Ying Huang, James L. Fisher, Amy S. Ruppert, Dwight H. Owen, Erin M. Bertino, Kerry A. Rogers, Seema A. Bhat, Michael R. Grever, Samantha M. Jaglowski, Kami J. Maddocks, John C. Byrd, Jennifer A. Woyach
Journal: Leukemia (2020)
SEVERE ASTHMATIC DYSPNEA AS THE SOLE PRESENTING SYMPTOM OF GENERALIZED ENDOLYMPHATIC CARCINOMATOSIS
Authors: Albert I. Mendeloff
Journal: Annals of Internal Medicine (2020)

Excerpt It is common knowledge today that respiratory symptoms are not infrequent manifestations of malignant disease arising elsewhere than in the lungs. Metastases to the lung are of fairly commo...
Baseline VDJ clonotype detection using a targeted sequencing NGS assay: allowing for subsequent MRD assessment
Authors: Malin Hultcrantz, Even Holth Rustad, Venkata Yellapantula, Maria Arcila, Caleb Ho, Mustafa H. Syed, Elli Papaemmanuil, Yanming Zhang, Francesco Maura, Ola Landgren
Journal: Blood Cancer Journal (2020)
A biphasic gene expression response to cisplatin treatment in ovarian cancer: An immediate early gene response followed by a p53 response
Authors: Jianghong Li, William Wood, Kevin Becker, Ashani Weeraratna, Patrice J. Morin
Journal: Cancer Research (2006)

1393  The molecular pathways activated in response to acute cisplatin exposure, as well as the mechanisms involved in the development of cisplatin resistant cancer cells remain unclear. Using whole genome oligonucleotide microarrays, we have examined the kinetic of gene expression changes in cisplatin sensitive and resistant ovarian cancer cells. Both cell lines used exhibited a response characterized by a biphasic pattern of gene expression with a first major cluster of induced genes detectable after 2 hours and a second wave of genes induced at 16-24 hours. The major cluster of genes associated with the initial response consisted of several immediate early genes (IEG), suggesting a MAPK-regulated response. Consistent with this hypothesis, ERK1/2 phosphorylation was sharply increased within two hours in these lines. Beginning at 16 hours of cisplatin treatment, a strong induction of several known p53-regulated genes could be observed and this induction corresponded to a significant increase in p53 protein levels. Because the initial MAPK induction is likely important in both responses, this pathway may be crucial in determining the cancer cell sensitivity to cisplatin and thus represent a promising pathway for therapy. Consistent with this hypothesis, inhibition of the MAPK pathway during cisplatin treatment led to a large increase in cell survival. In contrast, inhibition of p53 or its downstream target p21, led to a modest 2-fold decrease in cell survival. In addition, our analysis also allowed the identification of several genes that are differentially expressed between sensitive and resistant cells, including the gene encoding connexin 43, a highly upregulated protein in cisplatin-resistant cells. The pathways we identified in the cisplatin response, as well as the genes found differentially expressed between cisplatin resistant and sensitive cells may represent targets for therapy aimed at reversing drug resistance.
Making Sense of the Noise: Toward Rational Treatment for Obstructive Sleep Apnea
Authors: Eric J. Kezirian, Michael Simmons, Richard J. Schwab, Peter Cistulli, Kasey K. Li, Edward M. Weaver, Andrew N. Goldberg, Atul Malhotra
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

There has been a recent surge in the number of potential alternative therapies that have been proposed and marketed for adults with OSA. This Perspective finds that many of these alternatives do no...
Abstract 12924: Inhibition of microRNA-34a Protects against Aging and Progeria Associated Cardiac Dysfunction by Interfering with Telomere Shortening and DNA Damage Response Pathways
Authors: Reinier Boon, Kazuma Iekushi, Stefanie Lechner, Timon Seeger, Ariane Fischer, Susanne Heydt, Zenawit Girmatsion, Peter Biliczki, Joachim Ehrlich, Michael Potente, Andreas Zeiher, Heiko Hermeking, Stefanie Dimmeler
Journal: Circulation (2012)

Aging is the major risk factor for complications like acute myocardial infarction (AMI) and chronic heart failure. The mechanisms involved in cardiovascular aging are poorly understood, but miRNAs ...
Abstract 12808: Cardiovascular Outcomes With Glucagon-Like Peptide 1 Agonists and Sodium-Glucose Cotransporter 2 Inhibitors in Patients With Type 2 Diabetes: A Meta-Analysis
Authors: Yeong-Min Lee, Eun-Ji Park, Young-Ah Park, Jeong-Sook Seo, Han-Young Jin, Tae-Hyun Yang, Dae-Kyung Kim, Dong-Soo Kim, Jae-Sik Jang
Journal: Circulation (2019)

Introduction: Considering that there were no head-to-head studies comparing the efficacy of different antidiabetic medications among patients who do not reach their glycemic goal, we investigated t...
The role of uteroglobin in the immunomodulation of non-small cell lung cancer
Authors: Jung Min Yoon, Jae-Jun Lim, Chul-Gyu Yoo, Choon-Taek Lee, Sung Koo Han, Young-Soo Shim, Young Whan Kim
Journal: Cancer Research (2005)

735  We have examined the possibility of developing immunological therapy against not tumor cells but the endothelial cells of newly formed vessels supporting tumor. In tumor models using A2/Kb transgenic mice, vaccination with the HLA-A2 restricted epitope peptides of VEGFR2 significantly suppressed the growth of multiple types of tumors in vivo even in a therapeutic setting. In anti-angiogenesis assay termed dorsal air sac (DAS) assay, tumor-induced angiogenesis was significantly suppressed with such peptide vaccination. In this report, we analyzed the mechanism of this novel vaccination strategy against cancer.Vaccination using the HLA-A2 restricted epitope peptides (R2-773, -775, -1084) showed significant suppression of the tumor growth in A2/Kb mouse tumor model. Furthermore, vaccination using these peptides showed equivalent anti-tumor-angiogenesis effects in DAS assay. To examine adverse effects of the vaccination on physiological angiogenesis, we analyzed wound healing in mice treated with the vaccination. Delay of the wound healing was observed in mice vaccinated by R2-775 or R2-1084 peptide, whereas such delay was not observed in the mice vaccinated with R2-773 peptide. Interestingly, splenocytes of the mice vaccinated with R2-773 peptide showed the secretion of IFN-γ upon stimulation with the cells pulsed with the peptide without showing the cytotoxicity against those cells in vitro. However, splenocytes of the mice vaccinated with R2-775 or R2-1084 peptides showed both the secretion of IFN-γand cytotoxicity. These results may indicate that cytotoxicity of the CTLs induced by peptide vaccination was related to delay of the wound healing. To examine the involvement of IFN-γin anti-tumor-angiogenesis effects with the peptide vaccine, we performed in vivo blocking assay using an antibody for Interferon-γ-inducible protein 10 (IP10), which is one of the IFN-γ-inducing chemokines and showed to have direct effects on anti-angiogenesis. When the anti-IP10 antibody was inoculated, anti-tumor effect of the vaccination with R2-773 peptide were significantly suppressed. Furthermore, anti-angiogenesis effects were also suppressed in the mice vaccinated with R2-773 peptide. These results suggest that IFN-γand IP10 are involved in the mechanism of the anti-tumor effects of the peptide vaccination.
AB0914 BONE LOSS AND NEW FRACTURES WITH DENOSUMAB TREATMENT
Authors: C. Sanguesa, I. Casafont-Solé, A. Nack, S. Holgado Pérez, M. Martínez-Morillo, M. Aparicio Rovira, Á. Prior-Español, M. Aparicio Espinar, A. Riveros, L. Mateo, A. Olive, L. Gifre
Journal: Annals of the Rheumatic Diseases (2020)

Background: The incidence and factors related to an inadequate response to denosumab (Dmab) treatment remain unclear. Objectives: To describe clinical, analytical and densitometric characteristics of patients with inadequate response (IR) to Dmab in clinical practice. IR was defined as the presence of a new fracture [fxs-IR] or a significant decrease in BMD (≥5% lumbar or ≥4% femoral) [BMD-IR]. Methods: retrospective study of patients with IR to Dmab treatment. Data of demographic variables, risk factors for osteoporosis, history of fractures, previous anti-osteoporotic treatment, densitometric and analytical parameters were collected before and after IR. Results: 22 patients were included (19W:3M) with mean age of 75±10years. The causes of osteoporosis were: postmenopausal (50%), induced by glucocorticoids (22.7%), alcoholic (9.09%) and multifactorial (18.8%). Most patients were previously treated with bisphosphonates (59.09%, duration 5.2±2.6y) and had previous vertebral fractures (54.54% %, median 3). During Dmab treatment, 10 patients presented a BMD-IR (with a mean bone loss up to -3.5% at femur and -5.8% at lumbar spine) and 12 had fxs-IR (vertebral [n=8], humerus [n=1], pelvis [n=1], tibia [n=1]). No significant differences were observed in duration of Dmab between both IR groups (Fxs-IR: 3,2±1,9 vs BMD-IR: 2,4 ± 1,2y). In the BMD-IR, the BMD loss was higher at lumbar spine than at total hip (-6.6%±3.7 vs -1.9%±4.8). Only 1 patient of the fxs-IR had a secondary cause of IR (mieloma multiple). In the fxs-IR group, most patients started combined treatment with teriparatide (n=4), 1 changed to teriparatide and 7 remained with Dmab. In the BMD-IR group, most mantained Dmab treatment (n=8) and 2 switched to zoledronate. Conclusion: Most patients who developed IR to Dmab had been previously treated with bisphosphonates and had previous fragility fractures and appears within the first 3 years of treatment. BMD loss seems to be more marked at spine than total hip. Only one patient had a secundary cause of IR. Disclosure of Interests: None declared
COMPARABLE SURVIVAL OF CRITICALLY ILL PATIENTS ADMITTED TO THE ICU FOLLOWING REDUCED INTENSITY AND MS ELOABLATIVE CONDITIONLNG ALLOGENEIC STEM CELL TRANSPLANTATION
Authors: P.L.J. van der Heiden, Arbous, W. van Beers, W.M. van den Bergh, C. Hess, N. Kusadasi, W.A.F. Marijt, M.C. Muller, P.R. Tuinman, M. van Vliet, D.J. van Westerloo, N. Blijlevens, HemIC Study Grp
Journal: Intensive Care Medicine (2014)
Influenza-like illness is associated with high pneumococcal carriage density in Malawian children
Authors: Tinashe K. Nyazika, Alice Law, Todd D. Swarthout, Lusako Sibale, Danielle ter Braake, Neil French, Robert S. Heyderman, Dean Everett, Aras Kadioglu, Kondwani C. Jambo, Daniel R. Neill
Journal: Journal of Infection (2020)

High pneumococcal carriage density is a risk factor for invasive pneumococcal disease (IPD) and transmission, but factors that increase pneumococcal carriage density are still unclear.We undertook a cross-sectional study to evaluate the microbial composition, cytokine levels and pneumococcal carriage densities in samples from children presenting with an influenza-like illness (ILI) and asymptomatic healthy controls (HC).The proportion of children harbouring viral organisms (Relative risk (RR) 1.4, p = 0.0222) or ≥ 4 microbes at a time (RR 1.9, p < 0.0001), was higher in ILI patients than HC. ILI patients had higher IL-8 levels in nasal aspirates than HC (median [IQR], 265.7 [0 - 452.3] vs. 0 [0 - 127.3] pg/ml; p = 0.0154). Having an ILI was associated with higher pneumococcal carriage densities compared to HC (RR 4.2, p < 0.0001).These findings suggest that children with an ILI have an increased propensity for high pneumococcal carriage density. This could in part contribute to increased susceptibility to IPD and transmission in the community.
Abstract #5099: Increased growth inhibition and apoptosis using the novel combination of bortezomib and temsirolimus in non-Hodgkin\#8217;s lymphoma cell lines
Authors: James Shanks, Veena Fauble, Catherine Lobocki, Howard Terebelo
Journal: Cancer Research (2009)

Bortezomib is a selective, reversible inhibitor of the ubiquitin-proteasome pathway whose action leads to tumor growth arrest and induction of apoptosis. Bortezomib has demonstrated clinical activity in non-Hodgkin\#8217;s lymphoma (NHL), especially mantle cell lymphoma (MCL). The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that plays a key role in tumor cell growth and proliferation. Temsirolimus is an mTOR inhibitor that has shown activity in preclinical and clinical studies in various NHL subtypes. The objective of this study was to determine the growth inhibitory and apoptotic effects of the novel combination of bortezomib and temsirolimus in selected NHL cell lines including: Granta-519 (MCL), Toledo (large B-cell lymphoma), and EHEB (chronic B-cell leukemia). Cell viability was determined by the colorimetric MTS assay after 24 and 48 hours of treatment with bortezomib (1 - 10 nM) and temsirolimus (0.1 - 5 \#956;M). Drug interactions were examined by the combination-index (CI) isobologram method of median dose-effect analysis. Apoptosis was assessed by measuring cytochrome c release and caspase 3, 8, and 9 activity after 24 hours of treatment. Additionally, Bax and FasL expression, factors involved in pro-apoptotic signaling were evaluated by western blot analysis. The MTS assays revealed a significant time and dose-dependent growth inhibition with either agent alone in all three NHL subtypes. A synergistic interaction was demonstrated with bortezomib and temsirolimus in the EHEB and Granta-519 cell lines, while an additive effect was seen at lower drug doses in the Toledo cell line. The LD50 ranged from 2.7 - 9.2 nM for bortezomib alone and 0.3 - 10.6 \#956;M for temsirolimus alone. These levels were reduced to 0.4 - 4.5 nM and 0.04 - 2.25 \#956;M for bortezomib and temsirolimus, respectively, when these drugs were used in combination. A 4 to 10-fold (bortezomib) and 2 to 8-fold (temsirolimus) increase in caspase-3 activity was seen, which was increased 8 to 24-fold (p   Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5099.
Exploiting DNA repair defects in breast cancer
Authors: K.A.T. Naipal, N.S. Verkaik, P. ter Brugge, N. Ameziane, C.H.M. van Deurzen, J.W. Martens, J.P. de Winter, J. Jonkers, M.P. Vreeswijk, A. Jager, J. Hoeijmakers, R. Kanaar, D.C. van Gent
Journal: Cancer Research (2014)