Objective: Heterocyclic amines (HCAs) are mutagens and carcinogens primarily generated when cooking meat at high temperatures or until well-done, and their major metabolic pathway includes hepatic N-hydroxylation via CYP1A2 followed by O-acetylation via N-acetyltransferase 2 (NAT2). NAT2 expresses a well-defined genetic polymorphism in humans resulting in rapid and slow acetylators. Recent epidemiological studies reported significant associations between dietary HCA exposure and insulin resistance and type II diabetes.
View Article and Find Full Text PDFWe strive to overcome the challenges posed by ring artifacts in X-ray computed tomography (CT) by developing a novel approach for generating training data for deep learning-based methods. Training such networks require large, high quality, datasets that are often generated in the data domain, time-consuming and expensive. Our objective is to develop a technique for synthesizing realistic ring artifacts directly in the image domain, enabling scalable production of training data without relying on specific imaging system physics.
View Article and Find Full Text PDFBackground: Reducing unnecessary emergency department (ED) visits following joint arthroplasty is an important goal. Literature suggests 30-day visit rates range between 4% and 15%, with only 20%-25% of these admitted for care. Low admissions suggest an opportunity to reduce unnecessary postarthroplasty ED visits.
View Article and Find Full Text PDF3,4-Dimethylaniline (3,4-DMA) is present in cigarette smoke and widely used as an intermediate in dyes, drugs, and pesticides. Nucleotide excision repair-deficient Chinese hamster ovary (CHO) cells stably transfected with human CYP1A2 and N-acetyltransferase 1 (NAT1) alleles: (reference allele) or (the most common variant allele) were utilized to assess 3,4-DMA -acetylation and hypoxanthine phosphoribosyl transferase (HPRT) mutations, double-strand DNA breaks and reactive oxygen species (ROS). CHO cells expressing exhibited significantly ( < 0.
View Article and Find Full Text PDFBackground: The National Clinical Trials Network (NCTN) is the largest government sponsored organization in the United States tasked with funding randomized controlled trials (RCTs) in oncology. It is unknown whether there are differences in study design by treatment modality. We evaluated differences in methodology between trials testing radiotherapy versus systemic therapy.
View Article and Find Full Text PDFJ Med Imaging (Bellingham)
December 2024
Purpose: Proton radiation therapy may achieve precise dose delivery to the tumor while sparing non-cancerous surrounding tissue, owing to the distinct Bragg peaks of protons. Aligning the high-dose region with the tumor requires accurate estimates of the proton stopping power ratio (SPR) of patient tissues, commonly derived from computed tomography (CT) image data. Photon-counting detectors for CT have demonstrated advantages over their energy-integrating counterparts, such as improved quantitative imaging, higher spatial resolution, and filtering of electronic noise.
View Article and Find Full Text PDFObjectives: Approximately 30% of non-metastatic anal squamous cell carcinoma (ASCC) patients will experience recurrence after chemoradiotherapy (CRT), and currently available clinical variables are poor predictors of treatment response. We aimed to develop a model leveraging information extracted from radiation pretreatment planning CT to predict recurrence-free survival (RFS) in ASCC patients after CRT.
Methods: Radiomics features were extracted from planning CT images of 96 ASCC patients.
Deep learning (DL) has proven to be important for computed tomography (CT) image denoising. However, such models are usually trained under supervision, requiring paired data that may be difficult to obtain in practice. Diffusion models offer unsupervised means of solving a wide range of inverse problems via posterior sampling.
View Article and Find Full Text PDFIntroduction: Disparities in incidence and outcome of rectal cancer are multifactorial in etiology but may be due, in part, to differences in gut microbiome composition. We used serial robust statistical approaches to assess baseline gut microbiome composition in a diverse cohort of patients with rectal cancer receiving definitive treatment.
Methods: Microbiome composition was compared by age at diagnosis (< 50 vs ≥ 50 years), race and ethnicity (White Hispanic vs non-Hispanic), and response to therapy.
Background: There are known disparities in incidence and outcomes of colorectal cancer (CRC) by race and ethnicity. Some of these disparities may be mediated by molecular changes in tumors that occur at different rates across populations. Genetic ancestry is a measure complementary to race and ethnicity that can overcome missing data issues and better capture genetic similarity in admixed populations.
View Article and Find Full Text PDFWaterpipe smoking is increasingly popular and understanding how chemicals found in hookah smoke may be harmful to human bronchial epithelial cells is of great importance. 4,4'-Oxydianiline (ODA), is an aromatic amine which is present at comparatively high levels in hookah smoke. The metabolism and the subsequent toxicity of ODA in human bronchial epithelial cells remains unknown.
View Article and Find Full Text PDFCardiovasc Toxicol
August 2024
Metabolic dysfunction associated-steatotic liver disease (MASLD)/metabolic dysfunction-associated steatohepatitis (MASH) is the liver manifestation of metabolic syndrome, which is characterized by insulin resistance, hyperglycemia, hypertension, dyslipidemia, and/or obesity. Environmental pollutant exposure has been recently identified as a risk factor for developing MASH. Heterocyclic amines (HCAs) are mutagens generated when cooking meat at high temperatures or until well-done.
View Article and Find Full Text PDFThe effectiveness of colonoscopy to reduce colorectal cancer (CRC) mortality is extrapolated from cohort studies in the absence of randomized controlled trial (RCT) data, whereas flexible sigmoidoscopy is supported by RCT data and may be easier to implement in practice. We characterized the anatomic distribution of CRC to determine the proportion that is visible with sigmoidoscopy. Patients with a primary diagnosis of colorectal adenocarcinoma were identified in the Surveillance, Epidemiology, and End Results program (2000-2020).
View Article and Find Full Text PDFHuman N-acetyltransferase 2 (NAT2) is subject to genetic polymorphism in human populations. In addition to the reference NAT2*4 allele, two genetic variant alleles (NAT2*5B and NAT2*7B) are common in Europe and Asia, respectively. NAT2*5B possesses a signature rs1801280 T341C (I114T) single-nucleotide polymorphism (SNP), whereas NAT2*7B possesses a signature rs1799931 G857A (G286E) SNP.
View Article and Find Full Text PDFThe I3- molecule is known to undergo substantial structural reorganization upon solvation by a protic solvent, e.g., water.
View Article and Find Full Text PDFObjectives: The effectiveness of colonoscopy to reduce colorectal cancer (CRC) mortality is extrapolated from cohort studies in the absence of randomized controlled trial (RCT) data, whereas flexible sigmoidoscopy is supported by RCT data and may be easier to implement in practice. We characterized the anatomic distribution of CRC to determine the proportion that is visible with sigmoidoscopy.
Methods: Patients with a primary diagnosis of colorectal adenocarcinoma were identified in the Surveillance, Epidemiology, and End Results program (2000-2020).
Heterocyclic amines (HCAs) are mutagenic compounds found in cooked meat. Recent epidemiological studies reported significant associations between dietary HCA exposure and insulin resistance and type II diabetes, and we recently reported that HCAs induce insulin resistance and glucose production in human hepatocytes. It is well known that HCAs require hepatic bioactivation by cytochrome P450 1A2 (CYP1A2) and N-acetyltransferase 2 (NAT2).
View Article and Find Full Text PDFPharmacogenet Genomics
August 2023
A novel haplotype in N -acetyltransferase 2 ( NAT2 ) composed of seven non-coding variants (rs1495741, rs4921913, rs4921914, rs4921915, rs146812806, rs35246381, and rs35570672) has been linked to dyslipidemia by multiple, independent genome-wide association studies. The haplotype is located approximately 14 kb downstream of NAT2-coding region (ch8:18,272,377-18,272,881; GRCh38/hg38) and represents a non-coding, intergenic haplotype. Interestingly, the same dyslipidemia NAT2 haplotype is also linked to urinary bladder cancer risk.
View Article and Find Full Text PDF4,4'-Methylenebis(2-chloroaniline) or MOCA is an aromatic amine used primarily in polyurethane and rubber industry. MOCA has been linked to hepatomas in animal studies while limited epidemiologic studies reported the association of exposure to MOCA and urinary bladder and breast cancer. We investigated MOCA-induced genotoxicity and oxidative stress in DNA repair-deficient Chinese hamster ovary (CHO) cells stably transfected with human metabolizing enzymes CYP1A2 and N-acetyltransferase 2 (NAT2) variants as well as in rapid, intermediate, and slow NAT2 acetylator cryopreserved human hepatocytes.
View Article and Find Full Text PDFBreast cancer is one of the leading causes of cancer death. Recent studies found that arylamine -acetyltransferase 1 (NAT1) is frequently upregulated in breast cancer, further suggesting NAT1 could be a potential therapeutic target for breast cancer. Previous publications have established that knockout (KO) in breast cancer cell lines leads to growth reduction both in vitro and in vivo and metabolic changes.
View Article and Find Full Text PDFBenzidine undergoes N-acetylation and following CYP1A2-catalyzed N-hydroxylation undergoes O-acetylation catalyzed by N-acetyltransferase 1 (NAT1). Benzidine exposure is associated with urinary bladder cancer but the effect of NAT1 genetic polymorphism on individual risk remains unclear. We used Chinese hamster ovary (CHO) cells transfected with human CYP1A2 and NAT1*4 allele (reference) or NAT1*14B (variant) to investigate the effects of dose and NAT1 polymorphism on benzidine metabolism and genotoxicity.
View Article and Find Full Text PDFArylamine N-acetyltransferase 2 (NAT2) is a phase II metabolic enzyme, best known for metabolism of aromatic amines and hydrazines. Genetic variants occurring in the NAT2 coding region have been well-defined and are known to affect the enzyme activity or protein stability. Individuals can be categorized into rapid, intermediate, and slow acetylator phenotypes that significantly alter their ability to metabolize arylamines, including drugs (e.
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