A5081216221- Lung Cancer Research Studies
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Glioma Diagnosis and Treatment
- Peptidase Inhibition and Analysis
- Cancer, Hypoxia, and Metabolism
- Monoclonal and Polyclonal Antibodies Research
- Lung Cancer Treatments and Mutations
- Lung Cancer Diagnosis and Treatment
- Immune Cell Function and Interaction
- Cancer Mechanisms and Therapy
- Neuroendocrine Tumor Research Advances
- Growth Hormone and Insulin-like Growth Factors
- Cancer, Lipids, and Metabolism
- Radiopharmaceutical Chemistry and Applications
- Radiomics and Machine Learning in Medical Imaging
- Cancer-related Molecular Pathways
- Melanoma and MAPK Pathways
- Medical Imaging and Pathology Studies
- Glycosylation and Glycoproteins Research
- Forensic Entomology and Diptera Studies
- Advanced X-ray and CT Imaging
- Histone Deacetylase Inhibitors Research
- Autoimmune Neurological Disorders and Treatments
- Computational Drug Discovery Methods
Fred Hutch Cancer Center
2016-2024
Centro Regional de Derechos Humanos y Justicia de Género, Corporación Humanas
2018
Johns Hopkins University
2013-2015
George Washington University
2015
Johns Hopkins Medicine
2015
Georgetown University
2013
University of Baltimore
2013
Alterations in EGFR, KRAS, and ALK are oncogenic drivers lung cancer, but how signaling influences immunity the tumor microenvironment is just beginning to be understood. Immunosuppression likely contributes because drugs that inhibit immune checkpoints like PD-1 PD-L1 have clinical benefit. Here, we show activation of AKT-mTOR pathway tightly regulates expression vitro vivo. Both IFNγ-mediated induction was dependent on mTOR. In human adenocarcinomas squamous cell carcinomas, membranous...
Despite decades of work, small-cell lung cancer (SCLC) remains a frustratingly recalcitrant disease. Both diagnosis and treatment are challenges: low-dose computed tomography (the approved method used for screening) is unable to reliably detect early SCLC, the malignancy's 5 year survival rate stands at paltry 7%. Clearly, development novel diagnostic therapeutic tools SCLC an urgent, unmet need. CD133 transmembrane protein that expressed low levels in normal tissue but overexpressed by...
Small cell lung cancer (SCLC) elicits the generation of autoantibodies that result in unique paraneoplastic neurological syndromes. The mechanistic basis for formation such is largely unknown but key to understanding their etiology. We developed a high-dimensional technique enables detection complex with native antigens directly from patient plasma. Here, we used our platform screen 1009 human plasma samples 3600 autoantibody-antigen complexes, finding patients SCLC harbors, on average,...
Rationale: Screening for non–small cell lung cancer is associated with earlier diagnosis and reduced mortality but also increased harm caused by invasive follow-up of benign pulmonary nodules. Lung tumorigenesis activates the immune system, components which could serve as tumor-specific biomarkers.Objectives: To profile tumor-derived autoantibodies peripheral biomarkers malignant nodules.Methods: High-density protein arrays were used to define specificity isolated from B cells 10 resected...
We have developed a somatic cell gene delivery mouse model of melanoma that allows for the rapid validation genetic alterations identified in this disease. A major advantage system is ability to multi-step process carcinogenesis immune-competent mice without generation and cross breeding multiple strains. used evaluate role RAS isoforms initiation context conditional Ink4a/Arf loss. Mice expressing tumor virus (TVA) receptor specifically melanocytes under control dopachrome tautomerase (DCT)...
<h3>Abstract</h3> The rapid spread of coronavirus disease (COVID-19) has greatly disrupted the livelihood many people around world. To date, more than 35.16 million COVID-19 cases with 1.037million total deaths have been reported worldwide. Compared China, where was first reported, COVID-19, number confirmed for in rest world incredibly high. Even though several dugs suggested to be used against disease, said interventions should backed by empirical clinical evidence. Therefore, this paper...
ABSTRACT The gap junction protein connexin 43 (Cx43) is a key player in wound healing, and inhibitors of Cx43, which speed epidermal are currently clinical trials. Here, we provide direct vivo evidence that specific phosphorylation events on Cx43 change the physiological response during healing. Blocking phosphorylation, through mutation serine residues at kinase C (PKC) or casein 1 (CK1) sites, significantly slowed rate closure vitro resulted thicker layer after reepithelialization....
Proteomic studies can offer information on hundreds to thousands of proteins and potentially provide researchers with a comprehensive understanding signaling response during stress disease. Large data sets, such as those obtained in high-dimensional proteomic studies, be leveraged for pathway analysis discover or describe the biological implications clinical disease states. Obesity is worldwide epidemic that considered risk factor numerous other diseases. We performed plasma from 3 separate...
Aberrant activation of rat sarcoma (Ras) signaling contributes to the development a variety human cancers, including gliomas. To determine dependence high-grade gliomas on continued Ras signaling, we developed doxycycline-regulated Kirsten (KRas) glioma mouse model. We previously demonstrated that KRas is required for maintenance glioblastoma multiforme tumors arising in context activated Akt vivo; inhibition expression resulted apoptotic tumor regression and significantly increased...
Targeted therapies have revolutionized cancer care, but the development of resistance remains a challenge in clinic. To identify rational targets for combination strategies, we used an established melanoma mouse model and selected resistant tumors following genetic suppression NRAS expression. Complete tumor regression was observed all mice, 40% recurred. Analysis showed that most common mechanism overexpression activation receptor tyrosine kinases (RTKs). Interestingly, commonly...
Abstract Despite the development of targeted drug therapies, lung cancer remains leading cause cancer-related death worldwide. Targeting immune checkpoints altered in cancer, such as T cell inhibitory receptors programmed 1 (PD-1) or CTLA4, represent promising new approaches to treatment. Here we investigated relationship activation PI3K/Akt/mTOR signaling pathway and expression suppressive ligand, PD-L1, non-small (NSCLC). NSCLC lines with mutations KRas, EGFR, BRaf, ALK RET had high levels...
Aberrant activation of the RAS signaling pathway contributes to nearly all human cancers, including gliomas. To determine dependence high-grade gliomas on this pathway, we developed a doxycycline-regulated KRas glioma mouse model. Using model previously demonstrated that inhibition expression in induced by activated and Akt results complete tumor regression. We have also shown that, context Ink4a/Arf loss, abrogation is sufficient decrease burden but resistance ensues. In study, sought...
The clinical management of patients with indeterminate pulmonary nodules is associated unintended harm to and better methods are required more precisely quantify lung cancer risk in this group. Here, we combine multiple noninvasive approaches accurately identify nodules. We analyzed 94 quantitative radiomic imaging features 41 qualitative semantic variables molecular biomarkers from blood derived an antibody-based microarray platform that determines protein, cancer-specific glycan,...
<div>Abstract<p>Alterations in EGFR, KRAS, and ALK are oncogenic drivers lung cancer, but how signaling influences immunity the tumor microenvironment is just beginning to be understood. Immunosuppression likely contributes because drugs that inhibit immune checkpoints like PD-1 PD-L1 have clinical benefit. Here, we show activation of AKT–mTOR pathway tightly regulates expression <i>in vitro</i> vivo</i>. Both IFNγ-mediated induction was dependent on mTOR. In...
Abstract Lung cancer is the leading cause of cancer-related mortality worldwide, and 85% lung cancers are associated with tobacco use. Activating mutations in K-ras have been identified ~25% adenocarcinomas found predominantly smokers. We previously demonstrated that reducing systemic IGF-1 levels, by treatment anti-diabetic drug metformin or liver-specific ablation gene, decreases tumorigenesis mouse models k-ras-driven cancer. Since preclinical clinical studies suggest diet composition...
Abstract High-risk smokers are currently being screened with low-dose CT imaging after the National Lung Screening Trial demonstrated a 20% reduction in lung cancer mortality. Unfortunately, small pulmonary nodules common finding (present 25-50%), very few (&lt;2.5%) ultimately determined to be cancer. We observed 4-fold increase tumor-associated B cells compared normal and hypothesized that lung-tumor derived autoantibodies could useful biomarkers for malignant nodule diagnosis. first...
Abstract Lung cancer is the leading cause of cancer-related mortality worldwide, and 85% lung cases are associated with tobacco use. Within this group, activating mutations in K-ras have been identified ∼25% adenocarcinomas. Using a mouse model k-ras-driven tumorigenesis, we previously demonstrated that deletion IGF-1 gene or reduction systemic levels using antidiabetic drug metformin markedly reduced tumor burden. Since preclinical clinical studies suggest diet composition best predictor...
<div>Abstract<p>Alterations in EGFR, KRAS, and ALK are oncogenic drivers lung cancer, but how signaling influences immunity the tumor microenvironment is just beginning to be understood. Immunosuppression likely contributes because drugs that inhibit immune checkpoints like PD-1 PD-L1 have clinical benefit. Here, we show activation of AKT–mTOR pathway tightly regulates expression <i>in vitro</i> vivo</i>. Both IFNγ-mediated induction was dependent on mTOR. In...