tbuckley/cabot-search huggingface dataset:
Abstract 2505: Fibrinogen suppresses tumor growth and metastasis in lung cancer
Authors: Xinran Wang, Mary Katherine Swartz, Runhua Liu
Journal: Cancer Research (2021)

Abstract About 80% to 85% of lung cancers are non-small cell lung cancers (NSCLC), including lung adenocarcinoma (LUAD, 40% of lung cancers) and lung squamous cell carcinoma (LUSC, 25% to 30% of lung cancers). Fibrinogen is an extracellular matrix protein composed of three polypeptide chains with fibrinogen alpha (FGA), beta (FGB), and gamma (FGG). A recent genome-scale screening reveals that loss of FGA affects the acceleration of tumor growth and metastasis of lung cancer, but the mechanism remains elusive. Based on our bioinformatics analysis, genetic alterations of FGA are unlikely to be a frequent event in human lung cancers. However, our expression analysis showed a low expression of FGA in human lung cancer tissues, including LUAD and LUSC. DNA hypermethylation in the promoter region of FGA is correlated with low expression of FGA in human LUAD tissues. Furthermore, FGA knockout promotes but the administration of FGA inhibits LUAD cell growth, migration, and invasion, as well as tumor colonization in the lung. Our functional analysis revealed the FGA-mediated regulation of tumor growth and metastasis through apoptosis and EMT is also involved in the integrin-AKT signaling pathway in LUAD cells in vitro and xenograft tumor model in vivo. These data suggest that FGA may play a suppressive role in LUAD cells to inhibit tumor growth and metastasis through induction of apoptosis and inhibition of EMT. In LUAD cells, FGA can bind integrin α5 and reduce phosphorylation of AKT, leading to an inhibition of mTOR signaling. The administration of FGA may provide a new therapeutic approach to inhibit LUAD cell growth and metastasis. However, FGA may also affect TME cells in vivo, such as endothelial cells, leading to the various roles of FGA in tumor growth and metastasis. Citation Format: Xinran Wang, Mary Katherine Swartz, Runhua Liu. Fibrinogen suppresses tumor growth and metastasis in lung cancer [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 2505.
Durable Humoral and Cellular Immune Responses 8 Months after Ad26.COV2.S Vaccination
Authors: Dan H Barouch, Kathryn E Stephenson, Jerald Sadoff, Jingyou Yu, Aiquan Chang, Makda Gebre, Katherine McMahan, Jinyan Liu, Abishek Chandrashekar, Shivani Patel, Mathieu Le Gars, Anne M de Groot, Dirk Heerwegh, Frank Struyf, Macaya Douoguih, Johan van Hoof, Hanneke Schuitemaker
Journal: New England Journal of Medicine (2021)

Durability of Response after Ad26.COV2.S Vaccination In this study, investigators measured immune responses in 20 participants who had received either one or two doses of the Ad26.COV2.S vaccine an...
Mitochondrial-triggered immune responses mechanistically connect drug-induced steatohepatitis and cardiomyopathy associated with nonalcoholic steatohepatitis
Authors: Haoran Wang, Sananda Pai, Shun Ishiyama, Xin Guo, Wei Dong Gao, Lakshmi Santhanam, Kathy Gabrielson, Dolores B. Njoku
Journal: Cellular and Molecular Immunology (2021)
Atrial fibrillation epidemiology, disparity and healthcare contacts: a population-wide study of 5.6 million individuals
Authors: Sheng-Chia Chung, Reecha Sofat, Dionisio Acosta-Mena, Julie A Taylor, Pier D Lambiase, Juan P Casas, Rui Providencia
Journal: The Lancet Regional Health - Europe (2021)

We aimed to evaluate atrial fibrillation occurrence, reasons for healthcare visits, mortality, causes of death and examined patterns by relative deprivation in the UK.
mRNA-1273 COVID-19 vaccine effectiveness against the B.1.1.7 and B.1.351 variants and severe COVID-19 disease in Qatar
Authors: Hiam Chemaitelly, Hadi M. Yassine, Fatiha M. Benslimane, Hebah A. Al Khatib, Patrick Tang, Mohammad R. Hasan, Joel A. Malek, Peter Coyle, Houssein H. Ayoub, Zaina Al Kanaani, Einas Al Kuwari, Andrew Jeremijenko, Anvar Hassan Kaleeckal, Ali Nizar Latif, Riyazuddin Mohammad Shaik, Hanan F. Abdul Rahim, Gheyath K. Nasrallah, Mohamed Ghaith Al Kuwari, Hamad Eid Al Romaihi, Mohamed H. Al-Thani, Abdullatif Al Khal, Adeel A. Butt, Roberto Bertollini, Laith J. Abu-Raddad
Journal: Nature Medicine (2021)
Abstract 1470: Preclinical activity of the first reversible, potent and selective inhibitor of EGFR exon 20 insertions
Authors: Franziska Siegel, Stephan Siegel, Keith Graham, Bethany Kaplan, Kirstin Petersen, Ulf Boemer, Uwe Eberspaecher, Daniel Korr, Ursula Moenning, Detlev Suelzle, Jens Schroeder, Florian Prinz, Sabine Zitzmann-Kolbe, Gizem Karsli-Uzunbas, Timothy Lewis, Mario Hermsen, Andrew Cherniack, Franz von Nussbaum, Knut Eis, Matthew Meyerson, Heidi Greulich
Journal: Cancer Research (2021)

Abstract Several targeted therapeutic options exist for non-small cell lung cancer (NSCLC) patients whose tumors harbor mutations of EGFR, including L858R, exon 19 deletions, and the acquired resistance mutation, T790M. However, there is no approved targeted therapy for patients with EGFR exon 20 insertions, highlighting an ongoing unmet medical need. Here, we describe a potent and selective inhibitor of EGFR exon 20 insertion mutants with decreased activity on the wild-type EGFR for an improved therapeutic window. Our compound, BAY-568, exhibits greater than 20-fold selectivity for EGFR exon 20 insertions compared to wild-type EGFR in isogenic Ba/F3 models and in cancer cell lines endogenously expressing EGFR exon 20 insertions. This activity is also observed in xenograft models in vivo, correlating with reductions in phospho-EGFR and phospho-Erk in tumors but not skin samples from treated mice. BAY-568 furthermore has even greater activity towards the “classical” erlotinib-sensitive mutations, L858R and exon 19 deletions. Importantly, our compound is reversible, differentiating it from other investigational compounds currently in clinical trials. Consistent with this, the presence of a C797S mutation, typically found in patients with acquired resistance to osimertinib, has no effect on the activity of BAY-568. Taken together, these results demonstrate the ability of BAY-568 to kill cancer cells harboring exon 20 insertions and other EGFR mutations with decreased activity on wild-type EGFR, irrespective of C797S mutation status. Citation Format: Franziska Siegel, Stephan Siegel, Keith Graham, Bethany Kaplan, Kirstin Petersen, Ulf Boemer, Uwe Eberspaecher, Daniel Korr, Ursula Moenning, Detlev Suelzle, Jens Schroeder, Florian Prinz, Sabine Zitzmann-Kolbe, Gizem Karsli-Uzunbas, Timothy Lewis, Mario Hermsen, Andrew Cherniack, Franz von Nussbaum, Knut Eis, Matthew Meyerson, Heidi Greulich. Preclinical activity of the first reversible, potent and selective inhibitor of EGFR exon 20 insertions [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 1470.
Abstract 281: pH-sensitive liposome for siRNA delivery to treat drug-resistant ovarian cancer
Authors: Kharimat Lora Alatise, Samantha Gardner, Angela Alexander-Bryant
Journal: Cancer Research (2021)

Abstract Introduction: With a 5-year survival rate of 47%, ovarian cancer is the 5th leading cause of death amongst women worldwide. Over 75% of patients experience recurrence after initial treatment, indicating a need for improved treatment options. Drug resistance is a major barrier hindering the success of current treatment methods. Our study analyzes the characteristics of a stimuli-sensitive liposomal delivery system for combatting drug resistance. Our delivery system will deliver bioactive siRNAs targeting genes related to drug resistance, cell proliferation, and apoptosis. In this study, we investigate the characteristics of the liposomes to determine particle size, surface charge, and ability to encapsulate/bind both siRNAs. We also begin to investigate the delivery potential of the pH-sensitive liposomal formulation in vitro using ovarian cancer cell lines. Methods: Empty and siRNA loaded cationic, pH-sensitive liposomes (CHEMS-LPs) were synthesized by the thin-film hydration method. Liposome size, zeta potential, and polydispersity index (PDI) were measured by dynamic light scattering (DLS). To measure siRNA encapsulation efficiency, fluorescently labeled siRNA was loaded into CHEMS-LPs and subjected to centrifugation to pellet the LPs. Fluorescence spectroscopy was used to detect siRNA in the supernatant. The toxicity of unloaded CHEMS-LPs was determined by an MTS assay using OVCAR3 (drug-sensitive) and OVCAR3-T40 (drug-resistant) human ovarian cancer cells. Results: The size and zeta potential of blank and siRNA-loaded CHEMS-LPs were 97.88 ± 2.39 nm and 29.0 ± 2.00 mV, and 80.78 ± 0.77​ nm and 13.1 ±1.66​ mV, respectively. The positively charged zeta potential confirms the cationic nature of our liposomes. The PDI demonstrated that the liposomes were unimodal and monodisperse with PDI values of less than 0.300 for each formulation. In addition, siRNA was successfully bound to CHEMS-LPs through electrostatic interaction with the cationic lipid layer, resulting in an encapsulation efficiency of 99.6% Conclusion: CHEMS-LPs are pH-sensitive, cationic, monodisperse liposomes able to encapsulate siRNAs in order to mediate delivery into ovarian cancer cells. Their stable structure, positive charge, and low cytotoxicity is promising for future studies, including delivery of bioactive siRNAs to stimulate downregulation of target genes related to drug resistance. Acknowledgements: This work was supported in part by the National Science Foundation EPSCoR Program under Award # OIA-1655740. We would like to thank George Duran from Stanford University for donating the OVCAR3-T40 cell line. Citation Format: Kharimat Lora Alatise, Samantha Gardner, Angela Alexander-Bryant. pH-sensitive liposome for siRNA delivery to treat drug-resistant ovarian cancer [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 281.
High-Dose Statin Therapy by Rosuvastatin Reduced Small-Dense LDL and MDA-LDL: The High-Dose Statin Therapy with Rosuvastatin for Lipid-lowing (SARD) Trial
Authors: Nishikido Toshiyuki, Kotooka Norihiko, Hikichi Yutaka, Oyama Junichi, Node Kouichi
Journal: Circulation (2015)
Antibiotic-driven intestinal dysbiosis in pediatric short bowel syndrome is associated with persistently altered microbiome functions and gut-derived bloodstream infections
Authors: Robert Thänert, Anna Thänert, Jocelyn Ou, Adam Bajinting, Carey-Ann D. Burnham, Holly J. Engelstad, Maria E. Tecos, I. Malick Ndao, Carla Hall-Moore, Colleen Rouggly-Nickless, Mike A. Carl, Deborah C. Rubin, Nicholas O. Davidson, Phillip I. Tarr, Barbara B. Warner, Gautam Dantas, Brad W. Warner
Journal: Gut Microbes (2021)

Surgical removal of the intestine, lifesaving in catastrophic gastrointestinal disorders of infancy, can result in a form of intestinal failure known as short bowel syndrome (SBS). Bloodstream infections (BSIs) are a major challenge in pediatric SBS management. BSIs require frequent antibiotic therapy, with ill-defined consequences for the gut microbiome and childhood health. Here, we combine serial stool collection, shotgun metagenomic sequencing, multivariate statistics and genome-resolved strain-tracking in a cohort of 19 patients with surgically-induced SBS to show that antibiotic-driven intestinal dysbiosis in SBS enriches for persistent intestinal colonization with BSI causative pathogens in SBS. Comparing the gut microbiome composition of SBS patients over the first 4 years of life to 19 age-matched term and 18 preterm controls, we find that SBS gut microbiota diversity and composition was persistently altered compared to controls. Commensals including Ruminococcus, Bifidobacterium, Eubacterium, and Clostridium species were depleted in SBS, while pathobionts (Enterococcus) were enriched. Integrating clinical covariates with gut microbiome composition in pediatric SBS, we identified dietary and antibiotic exposures as the main drivers of these alterations. Moreover, antibiotic resistance genes, specifically broad-spectrum efflux pumps, were at a higher abundance in SBS, while putatively beneficial microbiota functions, including amino acid and vitamin biosynthesis, were depleted. Moreover, using strain-tracking we found that the SBS gut microbiome harbors BSI causing pathogens, which can persist intestinally throughout the first years of life. The association between antibiotic-driven gut dysbiosis and enrichment of intestinal pathobionts isolated from BSI suggests that antibiotic treatment may predispose SBS patients to infection. Persistence of pathobionts and depletion of beneficial microbiota and functionalities in SBS highlights the need for microbiota-targeted interventions to prevent infection and facilitate intestinal adaptation.
Abstract 322: Protein expression shift and potential diagnostic markers through proteomics profiling of A549 lung cancer cells
Authors: Ayobami Matthew Olajuyin, Adefunke Kafayat Olajuyin, Ziqi Wang, Zhiwei Xu, Hayatu M. Raji, Malachy I. Okeke, Xiaoju Zhang
Journal: Cancer Research (2021)

Abstract Highlights:-Adenocarcinoma lung cancer is common but difficult to diagnose. - Little is known for its proteome when methanol extract of Calotropis procera was used for the treatment groups. -In the treatment versus control groups, about 413 proteins were upregulated while about 626 proteins were downregulated. -Some of the proteins are potential diagnostic markers. Objectives: Adenocarcinoma lung cancer is a common type of lung cancer but the therapeutic and diagnosis are problematic. We focused on the protein expression of Adenocarcinoma lung cancer using A549 cancer cells and unveiled novel diagnostic makers and mechanisms in which methanol extracts of Calotropis procera ameliorate the disease. Methods: A549 lung cancer cell lines were obtained and we have 3 control groups and 3 treatment groups. The treatment groups were treated with 80 ug/ml of methanol extracts of Calotropis procera leaf and proteins were extracted for tandem mass tag mass spectrometry. Differential protein expression was performed between treatment groups and controls and the identified proteins were analyzed for pathway enrichment. Selected proteins were further validated in another set of samples using a more quantitative method. Results: In the treatment versus control, about 413 proteins were upregulated while about 626 proteins were downregulated. Conclusion: This balanced proteomics method not only offers important understandings of protein expression and pathways but also discover potential diagnostic markers for adenocarcinoma lung cancer. It also reveals the molecular mechanisms in which the methanol extracts of Calotropis procera leaf prevent carcinogenesis. Citation Format: Ayobami Matthew Olajuyin, Adefunke Kafayat Olajuyin, Ziqi Wang, Zhiwei Xu, Hayatu M. Raji, Malachy I. Okeke, Xiaoju Zhang. Protein expression shift and potential diagnostic markers through proteomics profiling of A549 lung cancer 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 322.
Abstract 1269: Pharmacological targeting of transcription-replication conflict leads to anti-cancer efficacy with minimal side effects in preclinical models
Authors: Long Gu, Caroline Li, Robert Lingeman, Robert J. Hickey, Linda H. Malkas
Journal: Cancer Research (2021)

Abstract Unchecked growth of cancer cells places simultaneous demands on DNA replication and transcription. Targeting the transcription-replication conflict (TRC), a major source of genome instability, could have important therapeutic implications. However, testing this hypothesis is difficult without agents directly targeting TRC. Here, we report a small molecule ligand (AOH1996) of the replisome component PCNA, which stabilizes interaction between PCNA and the large subunit (rpb1) of RNA polymerase II through the APIM motif, resulting in proteasome-dependent degradation of rpb1 and lethal DNA damages. Orally administrable, AOH1996 suppresses tumor growth without discernable toxicity at more than 10 time the compound's effective dose. In addition, AOH1996 works synergistically with known DNA damage agents to kill cancer cells. These results reveal TRC as cancer-selective vulnerability and demonstrated the therapeutic potential of AOH1996. Citation Format: Long Gu, Caroline Li, Robert Lingeman, Robert J. Hickey, Linda H. Malkas. Pharmacological targeting of transcription-replication conflict leads to anti-cancer efficacy with minimal side effects in preclinical models [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 1269.
Plant-derived exosome-like nanoparticles and their therapeutic activities
Authors: Jisu Kim, Shiyi Li, Shuya Zhang, Jianxin Wang
Journal: Asian Journal of Pharmaceutical Sciences (2021)

Nanotechnologies have been successfully applied to the treatment of various diseases. Plant-derived exosome-like nanoparticles (PENs) are expected to become effective therapeutic modalities for treating disease or in drug-delivery. PENs are minimally cytotoxic to healthy tissues, with which they show excellent biocompatibility, and are biased towards tumors by targeting specific tissues through special endocytosis mechanisms. Thus, the use of these PENs may expand the scope of drug therapies while reducing the off-target effects. In this review, we summarize the fundamental features and bioactivities of PENs extracted from the grape, grapefruit, ginger, lemon, and broccoli and discuss the applications of these particles as therapeutics and nanocarriers.
Association of ultra-processed food intake with risk of inflammatory bowel disease: prospective cohort study
Authors: Neeraj Narula, Emily C L Wong, Mahshid Dehghan, Andrew Mente, Sumathy Rangarajan, Fernando Lanas, Patricio Lopez-Jaramillo, Priyanka Rohatgi, P V M Lakshmi, Ravi Prasad Varma, Andres Orlandini, Alvaro Avezum, Andreas Wielgosz, Paul Poirier, Majid A Almadi, Yuksel Altuntas, Kien Keat Ng, Jephat Chifamba, Karen Yeates, Thandi Puoane, Rasha Khatib, Rita Yusuf, Kristina Bengtsson Boström, Katarzyna Zatonska, Romaina Iqbal, Liu Weida, Zhu Yibing, Li Sidong, Antonio Dans, Afzalhussein Yusufali, Noushin Mohammadifard, John K Marshall, Paul Moayyedi, Walter Reinisch, Salim Yusuf
Journal: BMJ (2021)

To evaluate the relation between intake of ultra-processed food and risk of inflammatory bowel disease (IBD).Prospective cohort study.21 low, middle, and high income countries across seven geographical regions (Europe and North America, South America, Africa, Middle East, south Asia, South East Asia, and China).116 087 adults aged 35-70 years with at least one cycle of follow-up and complete baseline food frequency questionnaire (FFQ) data (country specific validated FFQs were used to document baseline dietary intake). Participants were followed prospectively at least every three years.The main outcome was development of IBD, including Crohn's disease or ulcerative colitis. Associations between ultra-processed food intake and risk of IBD were assessed using Cox proportional hazard multivariable models. Results are presented as hazard ratios with 95% confidence intervals.Participants were enrolled in the study between 2003 and 2016. During the median follow-up of 9.7 years (interquartile range 8.9-11.2 years), 467 participants developed incident IBD (90 with Crohn's disease and 377 with ulcerative colitis). After adjustment for potential confounding factors, higher intake of ultra-processed food was associated with a higher risk of incident IBD (hazard ratio 1.82, 95% confidence interval 1.22 to 2.72 for ≥5 servings/day and 1.67, 1.18 to 2.37 for 1-4 servings/day compared with <1 serving/day, P=0.006 for trend). Different subgroups of ultra-processed food, including soft drinks, refined sweetened foods, salty snacks, and processed meat, each were associated with higher hazard ratios for IBD. Results were consistent for Crohn's disease and ulcerative colitis with low heterogeneity. Intakes of white meat, red meat, dairy, starch, and fruit, vegetables, and legumes were not associated with incident IBD.Higher intake of ultra-processed food was positively associated with risk of IBD. Further studies are needed to identify the contributory factors within ultra-processed foods.ClinicalTrials.gov NCT03225586.
Abstract 1446: GRP78 targeting peptides deliver liposomal doxorubicin specifically to cancer and enhance the efficacy of radiation therapy
Authors: Abhay K. Singh, Chandresh Shyam, Calvin Lewis, Wendy Zhang, Sapna Deore, Vaishali Kapoor, Dennis E. Hallahan
Journal: Cancer Research (2021)

Abstract Traditional radiation therapy is often associated with significant toxicity to normal cells that could limit cancer therapy's success. The greater understanding of the molecular differences between cancer cells and normal cells has led to targeted therapies in cancer treatment. We discovered the radiation-inducible expression of Glucose regulated protein 78kDa (GRP78) in cancer using phage-display peptide libraries. In this study, we screened a peptide library and discovered novel peptides targeting GRP78. The top ten peptides were further evaluated for their affinity of binding to recombinant GRP78 using surface plasmon resonance technology. Since GRP78 is induced on cancer cells' surface, we irradiated the lung cancer cell lines A549 and H460 to evaluate peptide binding. Flow cytometry analysis of Dylight 488 conjugated peptides led to identifying peptides A and K with the highest binding level to irradiated A549 and H460. Peptides A and K were compared for their efficacy to deliver liposomal doxorubicin specifically to tumors. Copper-free click-chemistry was used to conjugate peptides to the liposome surface. Whole-body near-infrared imaging was performed to evaluate the biodistribution of the peptide conjugated liposomes in nude mice bearing A549 and H460 tumors. Both peptides A and K specifically delivered liposomes to the tumors compared to the non-targeted liposomes. In pilot tumor growth experiments, we found that GRP78 targeting peptide conjugated liposomes delayed the growth of tumors in nude mice compared to non-targeted liposomes. The inhibition of tumor growth was further enhanced in combination with radiation, indicating efficient delivery of the radiation-sensitizer doxorubicin specifically to tumors. Currently, studies are underway to evaluate the microscopic biodistribution of doxorubicin in tumor sections. Mass spectrometry analysis of various organs will be performed to determine the pharmacokinetics of liposomal doxorubicin delivered by GRP78 targeting peptides. In conclusion, our novel GRP78 targeting peptides specifically deliver liposomal doxorubicin to tumors. Doxorubicin encapsulated in GRP78 targeting peptide conjugated liposomes enhances the tumor growth inhibitory activity of radiation therapy. Specific delivery of radiation-sensitizing drugs encapsulated in a liposome by peptides that target radiation-inducible GRP78 is a promising therapeutic strategy for various cancers. Citation Format: Abhay K. Singh, Chandresh Shyam, Calvin Lewis, Wendy Zhang, Sapna Deore, Vaishali Kapoor, Dennis E. Hallahan. GRP78 targeting peptides deliver liposomal doxorubicin specifically to cancer and enhance the efficacy of radiation therapy [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 1446.
Geriatric assessment using G8 in patients who underwent major uro-oncologic surgery to predict postoperative complication: Comparison with Charlson comorbidity index
Authors: D.H. Park, S.H. Yoo, H.S. Yoon, G. Jung, J. Suh, H.D. Yuk, J.H. Ku, C. Kwak, H.H. Kim, C.W. Jeong
Journal: European Urology (2021)