A5080346583- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Cancer-related gene regulation
- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Lung Cancer Treatments and Mutations
- Histone Deacetylase Inhibitors Research
- Carcinogens and Genotoxicity Assessment
- Lung Cancer Research Studies
- Neonatal Respiratory Health Research
- Cancer-related Molecular Pathways
- Air Quality and Health Impacts
- DNA Repair Mechanisms
- Asthma and respiratory diseases
- Cancer Genomics and Diagnostics
- Cell death mechanisms and regulation
- Pediatric health and respiratory diseases
- Alcohol Consumption and Health Effects
- Click Chemistry and Applications
- Lung Cancer Diagnosis and Treatment
- Drug-Induced Hepatotoxicity and Protection
- Glycosylation and Glycoproteins Research
- Genomics, phytochemicals, and oxidative stress
- Ferroptosis and cancer prognosis
Lovelace Respiratory Research Institute
2016-2025
Biomedical Research Institute
2020-2025
UNM Comprehensive Cancer Center
2013-2024
University of New Mexico
1997-2024
New Mexico Cancer Center
1997-2024
Biomedical Research Institute of New Mexico
2021-2023
United States Food and Drug Administration
2022
Lovelace Medical Center
2018-2019
Cancer Genetics (United States)
2018
Instituto Nacional de Cancerología
2017
The p16 INK4a ( ) tumor suppressor gene can be inactivated by promoter region hypermethylation in many types including lung cancer, the leading cause of cancer-related deaths U.S. We have determined timing this event an animal model carcinogenesis and human squamous cell carcinomas (SCCs). In rat, 94% adenocarcinomas induced tobacco specific carcinogen 4-methylnitrosamino-1-(3-pyridyl)-1-butanone were hypermethylated at promoter; most important, methylation change was frequently detected...
Epigenetic alterations are strongly associated with the development of cancer. We conducted a phase I/II trial combined epigenetic therapy azacitidine and entinostat, inhibitors DNA methylation histone deacetylation, respectively, in extensively pretreated patients recurrent metastatic non-small cell lung This is well tolerated, objective responses were observed, including complete response partial patient who remains alive without disease progression approximately 2 years after completing...
Abstract Lung cancer is the leading cause of deaths worldwide, yet few genetic markers lung risk useful for screening exist. The let-7 family-of-microRNAs (miRNA) are global regulators important in controlling oncogene expression by binding to 3′ untranslated regions their target mRNAs. purpose this study was identify single nucleotide polymorphisms (SNP) that could modify and assess effect such SNPs on gene regulation non–small cell (NSCLC). complementary sites (LCS) were sequenced KRAS...
Despite optimal and early surgical treatment of non-small-cell lung cancer (NSCLC), many patients die recurrent NSCLC. We investigated the association between gene methylation recurrence tumor.Fifty-one with stage I NSCLC who underwent curative resection but had a within 40 months after (case patients) were matched on basis age, stage, sex, date surgery to 116 did not have (controls). whether seven genes in tumor lymph nodes was associated recurrence.In multivariate model, promoter...
Tobacco-related diseases such as lung cancer cause over 4.2 million deaths annually, with approximately 400,000 per year occurring in the US. Genotoxic effects of tobacco components have been described, but on signaling pathways normal cells not described. Here, we show activation serine/threonine kinase Akt nonimmortalized human airway epithelial vitro by two cigarette smoke, nicotine and tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Activation or NNK...
Tobacco-related diseases such as lung cancer cause over 4.2 million deaths annually, with approximately 400,000 per year occurring in the US. Genotoxic effects of tobacco components have been described, but on signaling pathways normal cells not described. Here, we show activation serine/threonine kinase Akt nonimmortalized human airway epithelial vitro by two cigarette smoke, nicotine and tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Activation or NNK...
Abstract A sensitive screening approach for lung cancer could markedly reduce the high mortality rate this disease. Previous studies have shown that methylation of gene promoters is present in exfoliated cells within sputum prior to diagnosis. The purpose current study conduct a nested case-control incident cases from an extremely high-risk cohort evaluating promoter 14 genes sputum. Controls (n = 92) were members matched 98) by gender, age, and month enrollment. comparison proximal...
Abstract Epithelial-to-mesenchymal transition (EMT) is strongly associated with cancer progression, but its potential role during premalignant development has not been studied. Here, we show that a 4-week exposure of immortalized human bronchial epithelial cells (HBEC) to tobacco carcinogens can induce persistent, irreversible, and multifaceted dedifferentiation program marked by EMT the emergence stem cell–like properties. induction was epigenetically driven, initially chromatin remodeling...
Purpose: CT screening can reduce death from lung cancer. We sought to improve the diagnostic accuracy of cancer using ultrasensitive methods and a cancer-specific gene panel detect DNA methylation in sputum plasma.Experimental Design: This is case-control study subjects with suspicious nodules on imaging. Plasma were obtained preoperatively. Cases (n = 150) had pathologic confirmation node-negative (stages I IIA) non-small cell Controls 60) non-cancer diagnoses. detected promoter...
We have developed a technique, methylation-specific PCR in situ hybridization (MSP-ISH), which allows for the methylation status of specific DNA sequences to be visualized individual cells. use MSP-ISH monitor timing and consequences aberrant hypermethylation p16 tumor suppresser gene during progression cancers lung cervix. Hypermethylation was localized only neoplastic cells both lesions invasive cancers, associated with loss protein expression. allowed us dissect surprising finding that...
The association between increased DNA-methyltransferase (DNA-MTase) activity and tumor development suggest a fundamental role for this enzyme in the initiation progression of cancer. A true functional DNA-MTase neoplastic process would be further substantiated if target cells affected by initiating carcinogen exhibit changes activity. This hypothesis was addressed examining alveolar type II (target) Clara (nontarget) from A/J C3H mice that high low susceptibility, respectively, lung...
Abstract Purpose: Lung cancer is the leading cause of mortality in United States, due part to lack a validated and effective screening approach for early detection. The prevalence methylation seven three genes was examined DNA from sputum plasma, respectively, women at different risk lung cancer. Experimental Design: survivors (n = 56), clinically cancer-free smokers 121), never 74) comprised study population. Plasma collected all groups, whereas smokers. Results: Methylation detected plasma...
Abstract The development of lung cancer is associated with aberrant promoter methylation and thus transcriptional silencing many tumor suppressor genes or critical for cellular maintenance. Here we report that the NADPH oxidases DUOX1 DUOX2, which are one main sources reactive oxygen species production in airway, frequently silenced human cancer. Screening cell lines revealed loss DUOX2 expression, was restored after treatment 5-aza 2′-deoxycytidine. Two genes, DUOXA1 DUOXA2,...
DNA methylation contributes to carcinogenesis by silencing key tumor suppressor genes. Here we report an ultrasensitive and reliable nanotechnology assay, MS-qFRET, for detection quantification of methylation. Bisulfite-modified is subjected PCR amplification with primers that would differentiate between methylated unmethylated DNA. Quantum dots are then used capture amplicons determine the status via fluorescence resonance energy transfer (FRET). Key features MS-qFRET include its low...
Wood smoke-associated chronic obstructive pulmonary disease (COPD) is common in women developing countries but has not been adequately described developed countries.Our objective was to determine whether wood smoke exposure a risk factor for COPD population of smokers the United States and aberrant gene promoter methylation sputum may modify this association.For cross-sectional study, 1,827 subjects were drawn from Lovelace Smokers' Cohort, predominantly female cohort smokers. self-reported....
Selenium has been reported to have chemopreventive benefits in lung cancer. We conducted a double-blind, placebo-controlled trial evaluate the incidence of second primary tumors (SPTs) patients with resected non-small-cell cancer (NSCLC) receiving selenium supplementation.Patients completely stage I NSCLC were randomly assigned take selenized yeast 200 μg versus placebo daily for 48 months. Participation was 6 36 months postoperatively and required negative mediastinal node biopsy, no...