tbuckley/cabot-search huggingface dataset:
Abstract 2024: Studying the effects of interfering with doxorubicin-induced senescence in human colon cancer HCT116 cells
Authors: Moureq Rashed Alotaibi, Homood As Sobeia, Munirah Alohaydib, Faten Alaqil, Khalid Alhazzani, Ali Alhoshani, Tareq Saleh, David Gewirtz
Journal: Cancer Research (2021)

Abstract Colorectal cancer (CRC) is type of cancer that growing in the colon or the rectum. Although CRC can be treated and managed through several means of therapy, the disease mortality is still high in Saudi Arabia. Upon treatment, cancer cells undergo different form of cell death or growth arrest such as apoptosis and senescence. Senescence is a state of proliferation arrest that is considered as a cause of drug resistance. The current study was designed to interfere with Doxorubicin-induced senescence in cancer cells, and shift the cytotoxicity of doxorubicin from proliferation arrest to apoptosis. β-galactosidase (β-gal) staining has demonstrated that Doxorubicin induces senescence in wild-type HCT116 but not in p21 knock-out cells. (DAPI)/TUNEL stating and Annexin V assay indicate that treatment with Doxorubicin promotes apoptosis in p21 knock-out HCT116 significantly more than in wild-type HCT116. β-galactosidase staining and 5-Dodecanoylaminofluorescein Di-β-D-Galactopyranosid (C12FDG) demonstrated that combination of Doxorubicin with Sorafenib, Rapamycin, or Venetoclax has significantly reduced senescence and induced more apoptosis as shown by Propidium iodide (PI)/Annexin v assay and Caspase 3/7 Assay. PCR data analysis demonstrated that not all combination of Doxorubicin with other agents significantly decreased expression of senescence protein, however, the results of this study provide findings that interference with senescence pathways may shift cytotoxicity from senescence to apoptosis. The authors extend their appreciation to the Deputyship for Research and Innovation, Ministry of Education in Saudi Arabia for partly funding this work through the project number (DRI-KSU-1273). Citation Format: Moureq Rashed Alotaibi, Homood As Sobeia, Munirah Alohaydib, Faten Alaqil, Khalid Alhazzani, Ali Alhoshani, Tareq Saleh, David Gewirtz. Studying the effects of interfering with doxorubicin-induced senescence in human colon cancer HCT116 cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2024.
Evaluation of the Effects of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19
Authors: Andreas Barratt-Due, Inge Christoffer Olsen, Katerina Nezvalova-Henriksen, Trine Kåsine, Fridtjof Lund-Johansen, Hedda Hoel, Aleksander Rygh Holten, Anders Tveita, Alexander Mathiessen, Mette Haugli, Ragnhild Eiken, Anders Benjamin Kildal, Åse Berg, Asgeir Johannessen, Lars Heggelund, Tuva Børresdatter Dahl, Karoline Hansen Skåra, Pawel Mielnik, Lan Ai Kieu Le, Lars Thoresen, Gernot Ernst, Dag Arne Lihaug Hoff, Hilde Skudal, Bård Reiakvam Kittang, Roy Bjørkholt Olsen, Birgitte Tholin, Carl Magnus Ystrøm, Nina Vibeche Skei, Trung Tran, Susanne Dudman, Jan Terje Andersen, Raisa Hannula, Olav Dalgard, Ane-Kristine Finbråten, Kristian Tonby, Bjorn Blomberg, Saad Aballi, Cathrine Fladeby, Anne Steffensen, Fredrik Müller, Anne Ma Dyrhol-Riise, Marius Trøseid, Pål Aukrust
Journal: Annals of Internal Medicine (2021)

New treatment modalities are urgently needed for patients with COVID-19. The World Health Organization (WHO) Solidarity trial showed no effect of remdesivir or hydroxychloroquine (HCQ) on mortality, but the antiviral effects of these drugs are not known.To evaluate the effects of remdesivir and HCQ on all-cause, in-hospital mortality; the degree of respiratory failure and inflammation; and viral clearance in the oropharynx.NOR-Solidarity is an independent, add-on, randomized controlled trial to the WHO Solidarity trial that included biobanking and 3 months of clinical follow-up (ClinicalTrials.gov: NCT04321616).23 hospitals in Norway.Eligible patients were adults hospitalized with confirmed SARS-CoV-2 infection.Between 28 March and 4 October 2020, a total of 185 patients were randomly assigned and 181 were included in the full analysis set. Patients received remdesivir (n = 42), HCQ (n = 52), or standard of care (SoC) (n = 87).In addition to the primary end point of WHO Solidarity, study-specific outcomes were viral clearance in oropharyngeal specimens, the degree of respiratory failure, and inflammatory variables.No significant differences were seen between treatment groups in mortality during hospitalization. There was a marked decrease in SARS-CoV-2 load in the oropharynx during the first week overall, with similar decreases and 10-day viral loads among the remdesivir, HCQ, and SoC groups. Remdesivir and HCQ did not affect the degree of respiratory failure or inflammatory variables in plasma or serum. The lack of antiviral effect was not associated with symptom duration, level of viral load, degree of inflammation, or presence of antibodies against SARS-CoV-2 at hospital admittance.The trial had no placebo group.Neither remdesivir nor HCQ affected viral clearance in hospitalized patients with COVID-19.National Clinical Therapy Research in the Specialist Health Services, Norway.
Survival outcomes of urothelial carcinoma with squamous differentiation versus pure squamous cell carcinoma
Authors: C. Lonati, L. Afferi, P. Baumeister, A. Minervini, A. Mari, W. Krajewski, M. Borghesi, M. Rink, F. Montorsi, A. Briganti, R. Hurle, R. Contieri, P. Umari, T. Klatte, J.Y-C. Teoh, F. Soria, C. Simeone, S. Zamboni, M. Roumiguié, M. Rouprêt, A. Masson-Lecomte, S.M.H. Einerhand, A. Mattei, M. Moschini
Journal: European Urology (2021)
Genome-encoded cytoplasmic double-stranded RNAs, found in <i>C9ORF72</i> ALS-FTD brain, propagate neuronal loss
Authors: Steven Rodriguez, Asli Sahin, Benjamin R. Schrank, Hawra Al-Lawati, Isabel Costantino, Eric Benz, Darian Fard, Alefiya D. Albers, Luxiang Cao, Alexis C. Gomez, Kyle Evans, Elena Ratti, Merit Cudkowicz, Matthew P. Frosch, Michael Talkowski, Peter K. Sorger, Bradley T. Hyman, Mark W. Albers
Journal: Science Translational Medicine (2021)

Triggers of innate immune signaling in the CNS of patients with amyotrophic lateral sclerosis and frontotemporal degeneration (ALS/FTD) remain elusive. We report the presence of cytoplasmic double-stranded RNA (cdsRNA), an established trigger of innate immunity, in ALS-FTD brains carrying
Cerebral Venous Sinus Thrombosis Caused by Neuro-Behçet Disease Accidentally Detected by 68Ga-FAPI PET/CT
Authors: Meiyan Lin, Qianqian Xue, Xin You, Shaobo Yao, Weibing Miao
Journal: Clinical Nuclear Medicine (2021)

Abstract A 26-year-old man presented with recurrent oral ulcer, temporal headache, and blurred vision for 4 months. The giant cell arteritis was suspected, and 18 F-FDG and 68 Ga-FAPI PET/CT were done. There was no hypermetabolic lesion in 18 F-FDG PET/CT. However, 68 Ga-FAPI PET/CT showed multiple increased FAPI uptake lesions in the cerebral venous sinus. High-resolution MR venography revealed multiple chronic cerebral venous sinus thrombosis. Neuro-Behçet disease was diagnosed finally. This case showed 68 Ga-FAPI PET/CT may play some role in the management of neuro-Behçet disease.
Abstract 2930: Characterization based on therapeutic target biomarkers of patients-driven xenografts model of gastric-type cervical adenocarcinoma
Authors: Yuki Kojima, Hiroshi Yoshida, Toshihiro Okuya, Hitomi S. Okuma, Tadaaki Nishikawa, Maki Tanioka, Kazuki Sudo, Emi Noguchi, Tatsunori Shimoi, Yasuhito Tanase, Masaya Uno, Mitsuya Ishikawa, Yasuhiro Fujiwara, Kan Yonemori, Tomoyasu Kato
Journal: Cancer Research (2021)

Abstract The majority of cervical adenocarcinomas are associated with human papillomavirus (HPV) mainly HPV types 18 and 16. Patients with gastric-type endocervical adenocarcinoma (GAS) have an aggressive clinical behavior, resulting in poor prognosis compared to those with HPV-associated usual type adenocarcinoma. Chemotherapy resistance to taxane and carboplatin-based regimen has also been reported, which poses a difficulty in managing GAS patients with metastatic lesion. We established patient-driven xenografts (PDX) of two GAS patients and evaluated protein biomarkers for drug development using immunohistochemistry staining. The pathological findings of the established PDX were confirmed by HE staining and special staining to be similar to the pathological findings obtained from the patients' surgical specimens. PDX was established 78 and 48 days after transplantation of patient tumor tissue into immunodeficient mice, respectively. HER2, HER3, PMS2, MSH6, PanTrk, and ARID1A were stained for both PDX and patient-tumor samples to evaluate biomarkers for therapeutic targets. All staining results were consistent between patient tumor samples and PDX for both patients. Staining results for HER3 showed that both patients' tumors and the corresponding PDXs were 3+. Staining for HER2 was 1+ in both cases. In all PDX and patient-tumor samaples, PMS2, MSH6 and ARID1A showed no loss of protein expression, and PanTrk showed no protein expression. In addition, nine additional tumor tissue specimens from GAS patients diagnosed at our institution were stained for HER3 and HER2. HER3 was 3+ in 3 cases and 2+ in 6 cases, and HER2 was 3+ in 1 case, 2+ in 3 cases and 1+ in 5 cases. The present study showed overexpression of HER2 and HER3, suggesting a therapeutic potential of targeting HER2 and/or HER3 in GAS patients. We are next planning an in vivo study to develop therapies in GAS patients. Citation Format: Yuki Kojima, Hiroshi Yoshida, Toshihiro Okuya, Hitomi S. Okuma, Tadaaki Nishikawa, Maki Tanioka, Kazuki Sudo, Emi Noguchi, Tatsunori Shimoi, Yasuhito Tanase, Masaya Uno, Mitsuya Ishikawa, Yasuhiro Fujiwara, Kan Yonemori, Tomoyasu Kato. Characterization based on therapeutic target biomarkers of patients-driven xenografts model of gastric-type cervical adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2930.
Abstract 2483: Expression of microRNA and mRNA in U87 glioblastoma cells transfected with PTEN
Authors: David Stefanik, Sidney Goldblatt, Rick Jordan
Journal: Cancer Research (2021)

Abstract Background: U87 glioblastoma cells (ATCC HTB-14) were transfected with a plasmid containing the wild type PTEN gene. Untransfected U87 cells and U87 cells transfected with a plasmid containing only a fluorescent marker served as controls. Methods: Cells were assessed for neurosphere formation and growth in soft agar. Genes were assessed for expression of microRNA and messenger RNA by the NanoString nCounter platform. Results: The PTEN transfectants exhibited reduced neurosphere formation and diminished growth in soft agar. The PTEN transfectants exhibited a 10-fold or greater change in 101 of 799 microRNA species assessed compared to untransfected cells. The change in microRNA expression was strongly influenced by growth in hypoxic conditions. Expression of mRNA was altered in 260 of 760 genes assessed with 8% of the genes showing a 10-fold or greater difference in expression level. A detailed summary of the NanoString results is provided. Conclusions: (1) The PTEN transfectants demonstrate growth characteristics in vitro suggestive of decreased tumorigenicity. (2) The expression level of multiple genes is affected in the PTEN transfectants. (3) Hypoxic conditions bring out the greatest change in the expression level of microRNA in the PTEN transfected cells. Citation Format: David Stefanik, Sidney Goldblatt, Rick Jordan. Expression of microRNA and mRNA in U87 glioblastoma cells transfected with PTEN [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2483.
Use of cast immobilisation versus removable brace in adults with an ankle fracture: multicentre randomised controlled trial
Authors: Rebecca Kearney, Rebecca McKeown, Helen Parsons, Aminul Haque, Nick Parsons, Henry Nwankwo, James Mason, Martin Underwood, Anthony C Redmond, Jaclyn Brown, Siobhan Kefford, Matthew Costa
Journal: BMJ (2021)

Abstract Objectives To assess function, quality of life, resource use, and complications in adults treated with plaster cast immobilisation versus a removable brace for ankle fracture. Design Multicentre randomised controlled trial. Setting 20 trauma units in the UK National Health Service. Participants 669 adults aged 18 years and older with an acute ankle fracture suitable for cast immobilisation: 334 were randomised to a plaster cast and 335 to a removable brace. Interventions A below the knee cast was applied and ankle range of movement exercises started on cast removal. The removable brace was fitted, and ankle range of movement exercises were started immediately. Main outcome measures Primary outcome was the Olerud Molander ankle score at 16 weeks, analysed by intention to treat. Secondary outcomes were Manchester-Oxford foot questionnaire, disability rating index, quality of life, and complications at 6, 10, and 16 weeks. Results The mean age of participants was 46 years (SD 17 years) and 381 (57%) were women. 502 (75%) participants completed the study. No statistically significant difference was found in the Olerud Molander ankle score between the cast and removable brace groups at 16 weeks (favours brace: 1.8, 95% confidence interval −2.0 to 5.6). No clinically significant differences were found in the Olerud Molander ankle scores at other time points, in the secondary unadjusted, imputed, or per protocol analyses. Conclusions Traditional plaster casting was not found to be superior to functional bracing in adults with an ankle fracture. No statistically difference was found in the Olerud Molander ankle score between the trial arms at 16 weeks. Trial registration ISRCTN registry ISRCTN15537280 .
Differences in Antipsychotic Treatment Discontinuation Among Veterans With Schizophrenia in the U.S. Department of Veterans Affairs
Authors: Mark Weiser, John M. Davis, Clayton H. Brown, Eric P. Slade, Li Juan Fang, Deborah R. Medoff, Robert W. Buchanan, Linda Levi, Michael Davidson, Julie Kreyenbuhl
Journal: American Journal of Psychiatry (2021)

Effectiveness of antipsychotic drugs is inferred from relatively small randomized clinical trials conducted with carefully selected and monitored participants. This evidence is not necessarily generalizable to individuals treated in daily clinical practice. The authors compared the clinical effectiveness between all oral and long-acting injectable (LAI) antipsychotic medications used in the treatment of schizophrenia in the U.S. Department of Veterans Affairs (VA) health care system.This was an observational study utilizing VA pharmacy data from 37,368 outpatient veterans with schizophrenia. Outcome measures were all-cause antipsychotic discontinuation and psychiatric hospitalizations. Oral olanzapine was used as the reference group.In multivariable analysis, clozapine (hazard ratio=0.43), aripiprazole long-acting injectable (LAI) (hazard ratio=0.71), paliperidone LAI (hazard ratio=0.76), antipsychotic polypharmacy (hazard ratio=0.77), and risperidone LAI (hazard ratio=0.91) were associated with reduced hazard of discontinuation compared with oral olanzapine. Oral first-generation antipsychotics (hazard ratio=1.16), oral risperidone (hazard ratio=1.15), oral aripiprazole (hazard ratio=1.14), oral ziprasidone (hazard ratio=1.13), and oral quetiapine (hazard ratio=1.11) were significantly associated with an increased risk of discontinuation compared with oral olanzapine. No treatment showed reduced risk of psychiatric hospitalization compared with oral olanzapine; quetiapine was associated with a 36% worse outcome in terms of hospitalizations compared with olanzapine.In a national sample of veterans with schizophrenia, those treated with clozapine, two of the LAI second-generation antipsychotics, and antipsychotic polypharmacy continued the same antipsychotic therapy for a longer period of time compared with the reference drug. This may reflect greater overall acceptability of these medications in clinical practice.
Abstract 1893: The dynamics of T cell clonal repertoire under targeted therapy vs. immunotherapy in melanoma
Authors: Lizhong Ding, Katie M. Campbell, Egmidio Medina, Kevin Chen, Willy Hugo
Journal: Cancer Research (2021)

Abstract Introduction. The current standard of care for metastatic melanoma patients utilizes either MAPK pathway inhibitors (MAPKi)-based targeted therapies or immune checkpoint inhibitors (ICI)-based immunotherapies. Almost every melanoma patient treated with MAPKi will relapse in a median of one year, whereas a small subset of ICI-treated melanoma patients experienced prolonged tumor control. Multiple reports have shown that both MAPKi and ICI treatment will induce increased T cell infiltration into the tumor. However, the T-cell receptor (TCR) clonotype dynamics across different therapies (MAPKi vs. ICI) and/or clinical response (responding vs. resistant) is still unknown. This study aims to compare the TCR repertoire dynamics and their associated tumor microenvironment (TME) phenotypes in melanoma pre- vs. post-ICI or MAPKi to see if there are unique patterns associated with better tumor control. Methods. Publicly available bulk RNA-seq data of 345 melanoma samples pre- and post- treatment were downloaded, including two MAPKi (n=116 tumors) and two ICI data sets (n = 229 tumors). All samples were classified into three groups: pre-treatment (PT), on-treatment responding (OT-R), and on-treatment non-responding (OT-NR). T cell clonotype and gene expression were quantified from the RNA-seq data using trust4 and HISAT2/htseq-count, respectively. Although the transcripts of T cells are mixed with tumor cells in the bulk RNA-seq data, the TCR clonotype abundance showed significant correlation with T cell marker expression, offering a measure of robustness in the identification of TCR from bulk tumor derived RNA-seq data. Results. Both MAPKi and ICI therapies significantly increase the TCR count, abundance, diversity, and clonality in OT-R samples compared to PT and OT-NR samples. Intriguingly, we observed significantly higher clonal replacement of PT samples' T cell clonotypes with novel, OT-specific clonotypes under both therapies. Of note, in the tumor subset that responded to the ICI, the increase of these novel TCR were significantly associated with the enrichment of naïve/memory CD4 and CD8 T cell signatures. Conclusions. In melanoma, intratumoral TCR dynamics patterns in response to MAPKi and ICI are mostly similar, except for the upregulation of naïve/memory T cell signatures in the subset of ICI-responder tumors. These insights may eventually lead to better markers for therapy-induced, productive anti-tumor immunity in melanoma. Citation Format: Lizhong Ding, Katie M. Campbell, Egmidio Medina, Kevin Chen, Willy Hugo. The dynamics of T cell clonal repertoire under targeted therapy vs. immunotherapy in melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1893.
Intravesical BCG induces a trained immunity phenotype in patients with non-muscle invasive bladder cancer
Authors: J.H. van Puffelen, B. Novakovic, L. Van Emst, J.L. Boormans, E. Oosterwijk, A.G. Van Der Heijden, M.G. Netea, L.A.B. Joosten, S.H. Vermeulen
Journal: European Urology (2021)
Potentiation of Gemcitabine and cytosine arabinoside (ara-C) cytotoxicity by the ribonucleotide reductase inhibitor triapine (3-AP) is schedule dependent
Authors: J. Sigmond, J. A. E. Kamphuis, A. C. Laan, G. J. Peters
Journal: Cancer Research (2005)

5106  Gemcitabine (Gemzar, dFdC) has multiple mechanisms of actions that include DNA/RNA incorporation and inhibition of ribonucleotide reductase (RR), leading to depletion of deoxynucleotide pools thereby self-potentiating its incorporation into DNA. Ara-C is also incorporated into DNA, but does not inhibit RR. Triapine (3-AP) is a new potent RR inhibitor with anti-tumor activity in vitro and in vivo, which is currently in clinical development. We aimed to investigate whether 3-AP would enhance cytotoxicity of dFdC and ara-C in non-small-cell lung cancer cells (NSCLC) and whether 3-AP would mediate this effect by an increase in the concentrations of the active metabolites dFdCTP and ara-CTP, substrates for DNA incorporation. Drug interactions were studied in the NSCLC cell lines A549, H292, H460 and SW1573 using the multiple drug effect analysis, which is expressed as the Combination Index (CI) (CI 1.1, antagonism). The accumulation of dFdCTP and ara-CTP was investigated using HPLC. Western blotting was used to determine the RR protein expression. All NSCLC cell lines were equally sensitive to 3-AP or dFdC. Using a constant molar ratio based on the IC50 concentrations of dFdC and 3-AP (1:200, respectively), both simultaneous and sequential exposure (preexposure to 3-AP for 24 hr) showed additivity and moderate antagonism. However, when 3-AP cells were preexposed to 3-AP at an IC25 concentration for 24 hr prior to variable concentrations of dFdC, strong synergism was found (CI: 0.3-0.7 in three cell lines) and slight antagonism in H460 cells. However, for ara-C which does not have any effect on RR much stronger synergism (CI: 0.2 in 3 cell lines and 0.77 in H460) was observed than for dFdC. In SW1573 (CIs 0.3 and 0.2) cells pretreatment with 3-AP stimulated both dFdCTP and ara-CTP accumulation 2-3 fold, but not in H460 (
Biodegradable cascade nanocatalysts enable tumor-microenvironment remodeling for controllable CO release and targeted/synergistic cancer nanotherapy
Authors: Jianrong Wu, Zheying Meng, Agata A. Exner, Xiaojun Cai, Xue Xie, Bing Hu, Yu Chen, Yuanyi Zheng
Journal: Biomaterials (2021)