tbuckley/cabot-search huggingface dataset:
Antagonistic effect of dexamethasone in temozolomide-induced apoptosis in human malignant glioblastoma T98G cells
Authors: Pratima Sur, Eric A. Sribnick, Sunil J. Patel, Swapan K. Ray, Naren L. Banik
Journal: Cancer Research (2005)

4040  The use of a steroid as supportive therapy in the treatment of brain tumors can effectively attenuate the increases in intracerebral blood pressure, which impairs regional blood flow. Steroid, however, may modulate the sensitivity of tumor cells to chemotherapeutic agents, which are used subsequently for induction of apoptotic death in tumor cells. Dexamethasone (DXM) is a steroid and commonly used as a supportive therapy to reduce the inflammation and cerebral edema associated with the growth of glioblastoma, which is the deadliest and most prevalent brain tumor in humans. Human patients with glioblastoma are frequently treated with DXM prior to chemotherapy. Many conventional chemotherapeutic agents remain mostly ineffective in controlling the malignant growth of glioblastomas. A new alkylating agent temozolomide (TMZ) has recently been found efficacious in the clinical trials in patients with various advanced malignancies, including glioblastomas. Under the physiological conditions, TMZ is spontaneously hydrolyzed to its active metabolite for methylation of DNA, triggering apoptotic death. But, any modulatory effect of DXM on the chemotherapeutic action of TMZ has not yet been evaluated experimentally in the cell culture or animal models. Therefore, in our current study, we have examined whether DXM acts as a synergistic or antagonistic agent during TMZ-induced apoptosis in human glioblastoma T98G cells in culture. T98G cells were pretreated with various doses of DXM followed by TMZ. The cell viability after 24 and 48 h was assessed by the trypan blue dye exclusion test. Wright staining and TUNEL assay were conducted to identify occurrence of apoptotic cell death based on the morphological and biochemical (DNA fragmentation) features, respectively. More biochemical features of apoptotic death, such as upregulation of Bax:Bcl-2 ratio, calpain activity, and caspase-3 activity were assessed by the Western blot analyses. A significant number of T98G cells committed apoptosis following treatment with 200 μM TMZ. However, a pretreatment of T98G cells with 100 μM or 200 μM DXM protected against TMZ-induced apoptosis, concomitantly decreasing the Bax:Bcl-2 ratio, calpain activity, and caspase-3 activity. These experimental results clearly indicate that DXM works as an antagonistic agent in combination with TMZ. Therefore, our investigation strongly implies that the combination of DXM and TMZ may be counteractive in treating human glioblastoma. Future studies should be conducted with the xenografted and allografted animal models of glioblastoma to confirm the in vivo antagonistic effect of DXM on TMZ action. Also, clinical studies in glioblastoma patients may shed new light in the controversial use of DXM in palliation of glioblastoma patients. This investigation was supported in part by the R01 grants from the NCI and NINDS of the NIH (Bethesda, MD), and also a grant from the State of SC.
Does Testicular Seminoma Involve a Higher Predisposition Than Nonseminoma to Develop Contralateral Testicular Tumors?
Authors: Klaus-Peter Dieckmann
Journal: Journal of Clinical Oncology (2021)

Blok et al 1 provide sound evidence for a dosedependent reduction of the risk of contralateral tumors in patients with testicular germ cell tumors (GCTs) by cisplatin-based chemotherapy, which is an effect that has been hypothesized since decades.
P01.03 Phase 1 Study of Patritumab Deruxtecan (HER3-DXd; U3-1402) in Combination with Osimertinib in Patients with Locally Advanced or Metastatic EGFR-mutated NSCLC
Authors: P. Jänne, R. Rajagopalan, G. Pudussery, P. Shrestha, S. Chen, R. Hodge, Y. Qiu, C. Yu
Journal: Journal of Thoracic Oncology (2021)
MA08.09 Clinical Management of Lung Adenocarcinoma Patients With HER2 V659E Mutation
Authors: Z. Jia, Y. Wang, Y. Wang, W. Wang, J. Ye, B. Li, H. Han-Zhang, J. Zhao, X. Zhang, F. Peng, F. Chen, X. Chen, Y. Lu, S. Ying, D. Wu, X. Zhang, C. Ma, L. Lai, S. Ma, S. Zhang, P. Liu, N. Liang
Journal: Journal of Thoracic Oncology (2021)
miR-375 prevents high-fat diet-induced insulin resistance and obesity by targeting the aryl hydrocarbon receptor and bacterial tryptophanase (<i>tnaA</i>) gene
Authors: Anil Kumar, Yi Ren, Kumaran Sundaram, Jingyao Mu, Mukesh K Sriwastva, Gerald W Dryden, Chao Lei, Lifeng Zhang, Jun Yan, Xiang Zhang, Juw Won Park, Michael L Merchant, Yun Teng, Huang-Ge Zhang
Journal: Theranostics (2021)

Diet manipulation is the basis for prevention of obesity and diabetes. The molecular mechanisms that mediate the diet-based prevention of insulin resistance are not well understood. Here, as proof-of-concept, ginger-derived nanoparticles (GDNP) were used for studying molecular mechanisms underlying GDNP mediated prevention of high-fat diet induced insulin resistance.
P89.05 Management of Patients with EGFR and ALK-Mutated Advanced Non-Small Cell Lung Cancer Post-TKI Therapy – A Real-World Survival Analysis
Authors: K. Kerrigan, S. Puri, J. Sinnott, B. Haaland, W. Akerley, S. Patel
Journal: Journal of Thoracic Oncology (2021)
P09.18 COVID-19 Outcomes in Patients With Thoracic Malignancies According to Gender and Ethnicity (TERAVOLT)
Authors: J. Whisenant, S. Wong, V. Torri, J. Revuelta, B. Halmos, G. Ceresoli, I. Monnet, S. Popat, O. Arrieta, M. Azab, A. Dingemans, J. Spasic, J. Van Meerbeeck, G. Recondo, N. Reinmuth, A. Valter, M. Unk, R. Ghalehtaki, D. Steinfort, J. Chorostowska-Wynimko, L. Viola, L. Horn, S. Peters, H.A. Wakelee, M.C. Garassino, U. Tapan
Journal: Journal of Thoracic Oncology (2021)
Resolving conflict: superordinate goals and careful communication
Authors: Ann Chapman
Journal: BMJ (2021)

<h3>Abstract</h3> Early life experiences affect the formation of neuronal networks, which can have a profound impact on brain function and behavior later in life. Previous work has shown that mice exposed to excessive sensory stimulation during development are hyperactive and novelty seeking, and display impaired cognition compared with controls. In this study, we addressed the issue of whether excessive sensory stimulation during development could alter behaviors related to addiction and underlying circuitry in CD-1 mice. We found that the reinforcing properties of cocaine were significantly enhanced in mice exposed to excessive sensory stimulation. Moreover, although these mice displayed hyperactivity that became more pronounced over time, they showed impaired persistence of cocaine-induced locomotor sensitization. These behavioral effects were associated with alterations in glutamatergic transmission in the nucleus accumbens and amygdala. Together, these findings suggest that excessive sensory stimulation in early life significantly alters drug reward and the neural circuits that regulate addiction and attention deficit hyperactivity. These observations highlight the consequences of early life experiences and may have important implications for children growing up in today’s complex technological environment.
Screening for tuberculosis among high-risk groups attending London emergency departments: a prospective observational study
Authors: Rishi K. Gupta, Swaib A. Lule, Maria Krutikov, Lara Gosce, Nathan Green, Jo Southern, Ambreen Imran, Robert W. Aldridge, Heinke Kunst, Marc Lipman, William Lynn, Helen Burgess, Asif Rahman, Dee Menezes, Ananna Rahman, Simon Tiberi, Peter J. White, Ibrahim Abubakar
Journal: European Respiratory Journal (2021)

<b>LTBI screening among high-risk groups at EDs could be implemented to identify those at risk of progression to TB disease. Large-scale studies are required to investigate effective TB disease screening strategies in EDs.</b>https://bit.ly/3bTkoOn
miR-23a/b suppress cGAS-mediated innate and autoimmunity
Authors: Qiuya Yu, Lei Chu, Yongxing Li, Quanyi Wang, Juanjuan Zhu, Chen Wang, Shufang Cui
Journal: Cellular and Molecular Immunology (2021)

Abstract Cyclic GMP-AMP synthase (cGAS), a key sensor of intracellular DNA, is essential for eliciting innate immunity against infection, whereas aberrant activation of cGAS by endogenous DNA promotes severe autoimmune diseases. However, it is largely unknown how cGAS expression is regulated during pathogen infection and autoimmunity. Here, we report that during herpes simplex virus type 1 (HSV-1) infection, two microRNAs (miR-23a and miR-23b) whose levels significantly decrease due to their interaction with the lncRNA Oasl2-209 directly regulate the expression of cGAS. Overexpression of miR-23a/b markedly dampens cytosolic DNA-induced innate immune responses, whereas inhibition of miR-23a/b enhances these responses. Mice treated with miR-23a/b agomirs exhibit increased susceptibility to HSV-1 infection. Moreover, cGAS is significantly upregulated in the Trex1 −/− mouse autoimmune disease model. Administration of miR-23a/b blunts self DNA-induced autoinflammatory responses in Trex1 −/− mice. Collectively, our study not only reveals a novel regulatory mechanism of cGAS expression by miRNAs but also identifies a potential therapy for cGAS-related autoimmune diseases.
GPs and trusts to overhaul communications systems after blind patient sent shielding letters she couldn’t read
Authors: Clare Dyer
Journal: BMJ (2021)

GPs and hospitals will have to make sure that patients who are blind or otherwise unable to access communications in the usual way are clearly identified, after the Department of Health and Social Care (DHSC) for England, faced by a High Court challenge, agreed to overhaul the system.

The department agreed to a court order obliging it to make the changes within four months just before the court case, brought by Sarah Leadbetter, who is registered blind and categorised as clinically extremely vulnerable, was about to be heard.

Leadbetter, 45, whose case was backed by the Equality and Human Rights Commission, was on the shielded patients …
Nicotinamide Mononucleotide Prevents Cisplatin-Induced Cognitive Impairments
Authors: Ki Hyun Yoo, Jason J. Tang, Mohammad Abdur Rashid, Chang Hoon Cho, Ana Corujo-Ramirez, Jonghoon Choi, Mun Gyeong Bae, Danielle Brogren, John R. Hawse, Xiaonan Hou, S. John Weroha, Alfredo Oliveros, Lindsey A. Kirkeby, Joseph A. Baur, Mi-Hyeon Jang
Journal: Cancer Research (2021)

Abstract Chemotherapy-induced cognitive impairment (CICI) is often reported as a neurotoxic side effect of chemotherapy. Although CICI has emerged as a significant medical problem, meaningful treatments are not currently available due to a lack of mechanistic understanding underlying CICI pathophysiology. Using the platinum-based chemotherapy cisplatin as a model for CICI, we show here that cisplatin suppresses nicotinamide adenine dinucleotide (NAD+) levels in the adult female mouse brain in vivo and in human cortical neurons derived from induced pluripotent stem cells in vitro. Increasing NAD+ levels through nicotinamide mononucleotide (NMN) administration prevented cisplatin-induced abnormalities in neural progenitor proliferation, neuronal morphogenesis, and cognitive function without affecting tumor growth and antitumor efficacy of cisplatin. Mechanistically, cisplatin inhibited expression of the NAD+ biosynthesis rate-limiting enzyme nicotinamide phosphoribosyl transferase (Nampt). Selective restoration of Nampt expression in adult-born neurons was sufficient to prevent cisplatin-induced defects in dendrite morphogenesis and memory function. Taken together, our findings suggest that aberrant Nampt-mediated NAD+ metabolic pathways may be a key contributor in cisplatin-induced neurogenic impairments, thus causally leading to memory dysfunction. Therefore, increasing NAD+ levels could represent a promising and safe therapeutic strategy for cisplatin-related neurotoxicity. Significance: Increasing NAD+ through NMN supplementation offers a potential therapeutic strategy to safely prevent cisplatin-induced cognitive impairments, thus providing hope for improved quality of life in cancer survivors.
Case fatality risk of the SARS-CoV-2 variant of concern B.1.1.7 in England, 16 November to 5 February
Authors: Daniel J Grint, Kevin Wing, Elizabeth Williamson, Helen I McDonald, Krishnan Bhaskaran, David Evans, Stephen JW Evans, Alex J Walker, George Hickman, Emily Nightingale, Anna Schultze, Christopher T Rentsch, Chris Bates, Jonathan Cockburn, Helen J Curtis, Caroline E Morton, Sebastian Bacon, Simon Davy, Angel YS Wong, Amir Mehrkar, Laurie Tomlinson, Ian J Douglas, Rohini Mathur, Paula Blomquist, Brian MacKenna, Peter Ingelsby, Richard Croker, John Parry, Frank Hester, Sam Harper, Nicholas J DeVito, Will Hulme, John Tazare, Ben Goldacre, Liam Smeeth, Rosalind M Eggo
Journal: Eurosurveillance (2021)

The SARS-CoV-2 B.1.1.7 variant of concern (VOC) is increasing in prevalence across Europe. Accurate estimation of disease severity associated with this VOC is critical for pandemic planning. We found increased risk of death for VOC compared with non-VOC cases in England (hazard ratio: 1.67; 95% confidence interval: 1.34–2.09; p &lt; 0.0001). Absolute risk of death by 28 days increased with age and comorbidities. This VOC has potential to spread faster with higher mortality than the pandemic to date.
Cardiac Magnetic Resonance for Early Detection of Radiation Therapy-Induced Cardiotoxicity in a Small Animal Model
Authors: El-Sayed H. Ibrahim, Dhiraj Baruah, Pierre Croisille, Jadranka Stojanovska, Jason C. Rubenstein, Anne Frei, Rachel A. Schlaak, Chieh-Yu Lin, Jamie L. Pipke, Angela Lemke, Zhiqiang Xu, Amanda Klaas, Michael Brehler, Michael J. Flister, Peter S. Laviolette, Elizabeth M. Gore, Carmen Bergom
Journal: JACC CardioOncology (2021)

Over one-half of all cancer patients receive radiation therapy (RT). However, radiation exposure to the heart can cause cardiotoxicity. Nevertheless, there is a paucity of data on RT-induced cardiac damage, with limited understanding of safe regional RT doses, early detection, prevention, and management. A common initial feature of cardiotoxicity is asymptomatic dysfunction, which, if left untreated, may progress to heart failure. The current paradigm for cardiotoxicity detection and management relies primarily upon assessment of ejection fraction. However, cardiac injury can occur without a clear change in ejection fraction. We sought to identify cardiac magnetic resonance (CMR) imaging markers of early RT-induced cardiac dysfunction. We investigated the effect of RT on global and regional cardiac function and myocardial T1/T2 values at 2 time points post-RT using CMR in a rat model of localized cardiac RT. Rats who received image-guided whole-heart radiation of 24 Gy were compared with sham-treated rats. The rats maintained normal global cardiac function post-RT. However, a deterioration in strain was particularly notable at 10 weeks post-RT, and changes in circumferential strain were larger than changes in radial or longitudinal strain. Compared with sham treatment, circumferential strain changes occurred at the basal, mid-ventricular, and apical levels (p < 0.05 for all at both 8 weeks and 10 weeks post-RT), most of the radial strain changes occurred at the mid-ventricular (p = 0.044 at 8 weeks post-RT) and basal (p = 0.018 at 10 weeks post-RT) levels, and most of the longitudinal strain changes occurred at the apical (p = 0.002 at 8 weeks post-RT) and basal (p = 0.035 at 10 weeks post-RT) levels. Regionally, lateral myocardial segments showed the greatest worsening in strain measurements, and histological changes supported these findings. Despite worsened myocardial strain post-RT, myocardial tissue displacement measures were maintained, or even increased. T1/T2 measurements showed small nonsignificant changes post-RT compared with values in nonirradiated rats. Our findings suggest MRI regional myocardial strain is a sensitive imaging biomarker for detecting RT-induced subclinical cardiac dysfunction before compromise of global cardiac function.
Lower Back Pain in a Patient With Sarcoma
Authors: Sebastian Mönch, Gabriel Scheubeck, Wolfgang G. Kunz
Journal: JAMA Oncology (2021)

A 39-year-old woman with alveolar rhabdomyosarcoma and bone metastases presents with lower back pain. The treatment regimen recently was changed to gemcitabine hydrochloride and docetaxel, and imaging shows edema in both psoas muscles. What is your diagnosis?
Diagnostic Pathways of Myeloma Patients Presenting to Hospital Care and Relationship to End Organ Damage: An Analysis from the Teamm (Tackling EArly Morbidity and Mortality in Myeloma) Trial in 977 Patients
Authors: Stella Bowcock, Catherine Atkin, Gulnaz Iqbal, Tim Planche, Guy Pratt, Kwee Yong, Jill Wood, Kerry Raynes, Eric Low, Helen Higgins, Janet Dunn, Mark T Drayson
Journal: Blood (2017)
Copy number loss in granzyme genes confers resistance to immune checkpoint inhibitor in nasopharyngeal carcinoma
Authors: Yuxiang Ma, Xi Chen, Ao Wang, Hongyun Zhao, Qingguang Lin, Hua Bao, Yang Zhang, Shaodong Hong, Wanxiangfu Tang, Yan Huang, Yunpeng Yang, Xue Wu, Yang Shao, Wenfeng Fang, Li Zhang
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Anti-programmed death (PD)-1 therapy has recently been used in recurrent or metastatic (R/M) nasopharyngeal carcinoma (NPC). The long-term survival and its biomarkers responding to anti-PD-1 treatment in patients with R/M NPC remain unclear. Methods Patients with R/M NPC were enrolled between March 2016 and January 2018 from two phase I clinical trials. The median follow-up period was 24.7 months. Eligible patients progressed on standard chemotherapy had measurable disease by Response Evaluation Criteria in Solid Tumor V.1.1. Non-obligatory contemporaneous tumor samples were collected for whole-exome sequencing. The primary outcome was objective response rate (ORR). Duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were secondary outcomes assessed in all patients. Results Among 124 evaluable patients, anti-PD-1 therapy achieved an ORR of 29.8% and a durable clinical benefit rate of 60.5%. The median OS (mOS) was 17.1 months (95% CI 14.2 to 24.7), median PFS (mPFS) was 3.8 months (95% CI 3.4 to 6.0), and median DOR was 9.5 months. Significant OS benefit from treatment was observed in patients without liver metastasis (23.8 vs 13.3 months, p=0.006). Copy number deletion in genes encoding granzyme B or granzyme H ( GZMB/H ) was associated with poor treatment outcome (mPFS altered vs wildtype: 1.7 vs 3.6 months, p=0.03; mOS altered vs wildtype: 10.1 vs 18 months, p=0.012). Conclusions Anti-PD-1 treatment provided promising clinical benefit in pretreated patients with R/M NPC. Copy number loss in either GZMB or GZMH genes was associated with reduced survival.
P78.01 Nivolumab in Second Line Non-Small Cell Lung Cancer – Comparing Real-World Outcomes in England to CheckMate (CM) 017 and 057
Authors: S. Popat, N. Tanna, S. Hartridge-Lambert, C. Kiff, A. Sowdani, B. Rothwell, T. Henrik-Brodtkorb, C. Ling, R. Smittenaar, M. Bomb, A. Turnbull, S. Lawton
Journal: Journal of Thoracic Oncology (2021)
The double-edged roles of ROS in cancer prevention and therapy
Authors: Yawei Wang, Huan Qi, Yu Liu, Chao Duan, Xiaolong Liu, Tian Xia, Di Chen, Hai-long Piao, Hong-Xu Liu
Journal: Theranostics (2021)

Reactive oxygen species (ROS) serve as cell signaling molecules generated in oxidative metabolism and are associated with a number of human diseases. The reprogramming of redox metabolism induces abnormal accumulation of ROS in cancer cells. It has been widely accepted that ROS play opposite roles in tumor growth, metastasis and apoptosis according to their different distributions, concentrations and durations in specific subcellular structures. These double-edged roles in cancer progression include the ROS-dependent malignant transformation and the oxidative stress-induced cell death. In this review, we summarize the notable literatures on ROS generation and scavenging, and discuss the related signal transduction networks and corresponding anticancer therapies. There is no doubt that an improved understanding of the sophisticated mechanism of redox biology is imperative to conquer cancer.
GLUT1 Expression in Tumor-Associated Neutrophils Promotes Lung Cancer Growth and Resistance to Radiotherapy
Authors: Pierre-Benoit Ancey, Caroline Contat, Gael Boivin, Silvia Sabatino, Justine Pascual, Nadine Zangger, Jean Yannis Perentes, Solange Peters, E. Dale Abel, David G. Kirsch, Jeffrey C. Rathmell, Marie-Catherine Vozenin, Etienne Meylan
Journal: Cancer Research (2021)

Abstract Neutrophils are the most abundant circulating leucocytes and are essential for innate immunity. In cancer, pro- or antitumor properties have been attributed to tumor-associated neutrophils (TAN). Here, focusing on TAN accumulation within lung tumors, we identify GLUT1 as an essential glucose transporter for their tumor supportive behavior. Compared with normal neutrophils, GLUT1 and glucose metabolism increased in TANs from a mouse model of lung adenocarcinoma. To elucidate the impact of glucose uptake on TANs, we used a strategy with two recombinases, dissociating tumor initiation from neutrophil-specific Glut1 deletion. Loss of GLUT1 accelerated neutrophil turnover in tumors and reduced a subset of TANs expressing SiglecF. In the absence of GLUT1 expression by TANs, tumor growth was diminished and the efficacy of radiotherapy was augmented. Our results demonstrate the importance of GLUT1 in TANs, which may affect their pro- versus antitumor behavior. These results also suggest targeting metabolic vulnerabilities to favor antitumor neutrophils. Significance: Lung tumor support and radiotherapy resistance depend on GLUT1-mediated glucose uptake in tumor-associated neutrophils, indicating that metabolic vulnerabilities should be considered to target both tumor cells as well as innate immune cells.
Cytosolic delivery of the immunological adjuvant Poly I:C and cytotoxic drug crystals via a carrier-free strategy significantly amplifies immune response
Authors: Xiaoqing Du, Yuqi Hou, Jia Huang, Yan Pang, Chenlu Ruan, Wei Wu, Chenjie Xu, Hongwei Zhang, Lifang Yin, Wei He
Journal: Acta Pharmaceutica Sinica B (2021)

Co-delivery of chemotherapeutics and immunostimulant or chemoimmunotherapy is an emerging strategy in cancer therapy. The precise control of the targeting and release of agents is critical in this methodology. This article proposes the asynchronous release of the chemotherapeutic agents and immunostimulants to realize the synergistic effect between chemotherapy and immunotherapy. To obtain a proof-of-concept, a co-delivery system was prepared via a drug-delivering-drug (DDD) strategy for cytosolic co-delivery of Poly I:C, a synthetic dsRNA analog to activate RIG-I signaling, and PTX, a commonly used chemotherapeutics, in which pure PTX nanorods were sequentially coated with Poly I:C and mannuronic acid via stimulating the RIG-I signaling axis. The co-delivery system with a diameter of 200 nm enables profound immunogenicity of cancer cells, exhibiting increased secretion of cytokines and chemokines, pronounced immune response in vivo, and significant inhibition of tumor growth. Also, we found that intracellularly sustained release of cytotoxic agents could elicit the immunogenicity of cancer cells. Overall, the intracellular asynchronous release of chemotherapeutics and immunomodulators is a promising strategy to promote the immunogenicity of cancer cells and augment the antitumor immune response.
P76.98 NSCLC Patients With Rare EGFR Mutations in Exons 18 and 19 Benefits From Treatment With EGFR Tyrosine Kinase Inhibitors
Authors: J. Xu, R. Guo, M. Li, J. Xiang, A. Lizaso, X. Mao, J. Ye, C. Xu, K. Chen
Journal: Journal of Thoracic Oncology (2021)
P77.05 Phase II Study of Imprime PGG and Pembrolizumab in Stage IV NSCLC After Progression on First-Line Therapy: BTCRC-LUN15-017
Authors: E. Sisel, M. Furqan, J. Malhotra, A. Shergill, K. Kennedy, L. Liu, M. Pasquinelli, L. Feldman
Journal: Journal of Thoracic Oncology (2021)