Interferon Induced Upregulation of Tripartite Motif 34 (TRIM34) Leads Apoptotic Cell Death in Lung Adenocarcinoma.

Despite breakthroughs in our understanding of lung cancer risk, development, immunologic control, and therapy choices, it remains one of the leading causes of cancer mortality. This study aimed to investigate the role of TRIM34 upon treatment of Interferon Gamma (IFN-γ) in Non-Small Cell Lung Cancer (NSCLC). NCI-H23 cells were exposed to IFN-γ in a dose- and time-dependent manner to understand TRIM34 expression and its role as a co-regulator of treatment.

α-Tocopherol Pharmacokinetics in Adults with Cystic Fibrosis: Benefits of Supplemental Vitamin C Administration.

Background: Numerous abnormalities in cystic fibrosis (CF) could influence tocopherol absorption, transportation, storage, metabolism and excretion. We hypothesized that the oxidative distress due to inflammation in CF increases vitamin E utilization, which could be positively influenced by supplemental vitamin C administration.

Methods: Immediately before and after receiving vitamin C (500 mg) twice daily for 3.

Circadian disruption in lung cancer.

Despite major developments in lung cancer investigations and the progress of innovative oncology treatments in recent decades, lung cancer continues to be the predominant cause of cancer-related mortality globally, with over a million deaths each year. This highlights the urgent need to develop a deeper understanding of the current state of cancer care. At the environmental and cellular levels, circadian rhythms are closely associated with living organisms.

Thermoresponsive liquid crystalline formulation of Exemestane: Design and structural characterization.

Exemestane (EXE), a drug used for the treatment of breast cancer, has limited aqueous solubility of 0.08 mg/mL and log P∼ 4.22.

The Kinome of Human Alveolar Type II and Basal Cells, and Its Reprogramming in Lung Cancer.

The discovery of mutant tyrosine kinases as oncogenic drivers of lung adenocarcinomas has changed the basic understanding of lung cancer development and therapy. Yet, expressed kinases (kinome) in lung cancer progenitor cells, as well as whether kinase expression and the overall kinome changes or is reprogrammed upon transformation, is incompletely understood. We hypothesized that the kinome differs between lung cancer progenitor cells, alveolar type II cells (ATII), and basal cells (BC) and that their respective kinomes undergo distinct lineage-specific reprogramming to adenocarcinomas and squamous cell carcinomas upon transformation.

Inhibition of the hexosamine biosynthetic pathway promotes castration-resistant prostate cancer.

The precise molecular alterations driving castration-resistant prostate cancer (CRPC) are not clearly understood. Using a novel network-based integrative approach, here, we show distinct alterations in the hexosamine biosynthetic pathway (HBP) to be critical for CRPC. Expression of HBP enzyme glucosamine-phosphate N-acetyltransferase 1 (GNPNAT1) is found to be significantly decreased in CRPC compared with localized prostate cancer (PCa).

Cigarette Smoke Induces Human Epidermal Receptor 2-Dependent Changes in Epithelial Permeability.

The airway epithelium constitutes a protective barrier against inhaled insults, such as viruses, bacteria, and toxic fumes, including cigarette smoke (CS). Maintenance of bronchial epithelial integrity is central for airway health, and defective epithelial barrier function contributes to the pathogenesis of CS-mediated diseases, such as chronic obstructive pulmonary disease. Although CS has been shown to increase epithelial permeability, current understanding of the mechanisms involved in CS-induced epithelial barrier disruption remains incomplete.

HER2 activation results in β-catenin-dependent changes in pulmonary epithelial permeability.

The receptor tyrosine kinase human epidermal growth factor receptor-2 (HER2) is known to regulate pulmonary epithelial barrier function; however, the mechanisms behind this effect remain unidentified. We hypothesized that HER2 signaling alters the epithelial barrier through an interaction with the adherens junction (AJ) protein β-catenin, leading to dissolution of the AJ. In quiescent pulmonary epithelial cells, HER2 and β-catenin colocalized along the lateral intercellular junction.

Bioinformatics-driven discovery of rational combination for overcoming EGFR-mutant lung cancer resistance to EGFR therapy.

Motivation: Non-small-cell lung cancer (NSCLC) is the leading cause of cancer death in the United States. Targeted tyrosine kinase inhibitors (TKIs) directed against the epidermal growth factor receptor (EGFR) have been widely and successfully used in treating NSCLC patients with activating EGFR mutations. Unfortunately, the duration of response is short-lived, and all patients eventually relapse by acquiring resistance mechanisms.

Contributions of KRAS and RAL in non-small-cell lung cancer growth and progression.

Introduction: KRAS mutations are poor prognostic markers for patients with non-small-cell lung cancer (NSCLC). RALA and RALB GTPases lie downstream of RAS and are implicated in RAS-mediated tumorigenesis. However, their biological or prognostic role in the context of KRAS mutation in NSCLC is unclear.

Evaluation of long-term vitamin E insufficiency or excess on bone mass, density, and microarchitecture in rodents.

High dietary α-tocopherol levels reportedly result in osteopenia in growing rats, whereas α-tocopherol deficiency in α-tocopherol transfer protein-knockout (α-TTP-KO) mice results in increased cancellous bone mass. Because osteoporosis is a disease associated primarily with aging, we hypothesized that age-related bone loss would be attenuated in α-TTP-KO mice. Cancellous and cortical bone mass and microarchitecture were assessed using dual-energy X-ray absorptiometry and micro-computed tomography in 2-year-old α-TTP-KO and wild-type (WT) male and female mice fed dl-α-tocopherol acetate.

Maternal obesity affects gene expression and cellular development in fetal brains.

Objectives: Female rat neonates reared on a high carbohydrate (HC) milk formula developed chronic hyperinsulinemia and adult-onset obesity (HC phenotype). Furthermore, we have shown that fetal development in the HC intrauterine environment (maternal obesity complicated with hyperinsulinemia, hyperleptinemia, and increased levels of proinflammatory markers) resulted in increased levels of serum insulin and leptin in term HC fetuses and the spontaneous transfer of the HC phenotype to the adult offspring. The objectives of this study are to identify changes in global gene expression pattern and cellular development in term HC fetal brains in response to growth in the adverse intrauterine environment of the obese HC female rat.

Bronchoalveolar lavage neuregulin-1 is elevated in acute lung injury and correlates with inflammation.

Shedding of neuregulin (NRG)-1 from the pulmonary epithelium leads to activation of the epithelial human epidermal growth factor receptor (HER)2 receptor, increased pulmonary epithelial permeability and acute lung injury (ALI). We sought to determine whether NRG-1 was detectable and elevated in bronchoalveolar lavage (BAL) and plasma from patients with ALI compared with controls and to determine whether a correlation exists between NRG-1 and inflammation and outcome in ALI. Matched BAL and plasma samples were obtained from 23 ALI patients requiring intubation and mechanical ventilation.

A high-fat diet containing whole walnuts (Juglans regia) reduces tumour size and growth along with plasma insulin-like growth factor 1 in the transgenic adenocarcinoma of the mouse prostate model.

Prostate cancer (PCa) has been linked to fat intake, but the effects of both different dietary fat levels and types remain inconsistent and incompletely characterised. The effects on PCa in the transgenic adenocarcinoma of the mouse prostate (TRAMP) cancer model of an elevated fat (20 % of energy as fat) diet containing 155 g of whole walnuts were compared to those of an elevated fat (20 % of energy as soyabean oil) diet with matched macronutrients, tocopherols as well as a low-fat (8 % of energy as soyabean oil) diet. Mice, starting at 8 weeks of age, consumed one of the three different diets ad libitum; and prostates, livers and blood were obtained after 9, 18 or 24 weeks of feeding.

Metabolomic profiling reveals potential markers and bioprocesses altered in bladder cancer progression.

Although alterations in xenobiotic metabolism are considered causal in the development of bladder cancer, the precise mechanisms involved are poorly understood. In this study, we used high-throughput mass spectrometry to measure over 2,000 compounds in 58 clinical specimens, identifying 35 metabolites which exhibited significant changes in bladder cancer. This metabolic signature distinguished both normal and benign bladder from bladder cancer.

Metabolomic profiling reveals a role for androgen in activating amino acid metabolism and methylation in prostate cancer cells.

Prostate cancer is the second leading cause of cancer related death in American men. Development and progression of clinically localized prostate cancer is highly dependent on androgen signaling. Metastatic tumors are initially responsive to anti-androgen therapy, however become resistant to this regimen upon progression.

Metabolites of purine nucleoside phosphorylase (NP) in serum have the potential to delineate pancreatic adenocarcinoma.

Pancreatic Adenocarcinoma (PDAC), the fourth highest cause of cancer related deaths in the United States, has the most aggressive presentation resulting in a very short median survival time for the affected patients. Early detection of PDAC is confounded by lack of specific markers that has motivated the use of high throughput molecular approaches to delineate potential biomarkers. To pursue identification of a distinct marker, this study profiled the secretory proteome in 16 PDAC, 2 carcinoma in situ (CIS) and 7 benign patients using label-free mass spectrometry coupled to 1D-SDS-PAGE and Strong Cation-Exchange Chromatography (SCX).

Evaluation of thiol-based antioxidant therapeutics in cystic fibrosis sputum: Focus on myeloperoxidase.

Neutrophil-dependent reactions catalysed by myeloperoxidase (MPO) are thought to play important roles in the pulmonary pathobiology of cystic fibrosis (CF). Aerosolized thiol antioxidants such as glutathione (GSH) and N-acetylcysteine (NAC) are currently being utilized as therapeutics to modify CF respiratory tract oxidative processes. This study hypothesized that MPO in CF airway lining fluids may be a target of such therapeutics.

Dietary alpha-tocopherol and neuromuscular health: search for optimal dose and molecular mechanisms continues!

Rodents fed alpha-tocopherol (alphaT)-depleted diets develop neuromuscular deficits. Unequivocal role of alphaT in the prevention of these deficits is confounded by possible neurotoxic oxidant products generated, ex vivo in alphaT-depleted diets. The discovery that large doses of alphaT could ameliorate neuromuscular deficits, attributed to very low serum alphaT caused by mutations in either the microsomal triglyceride transfer protein or the alphaT-transfer protein (alphaTTP), underscores the necessity of alphaT for neuromuscular health in humans.

Nr1d1, an important circadian pathway regulatory gene, is suppressed by cigarette smoke in murine lungs.

Nuclear receptor subfamily 1, group D member 1 (Nr1d1), also known as Rev-erb-alpha, belongs to the family of "orphan receptors" and functions as a member of clock gene family. In addition to being an important member of clock circuitry, Nr1d1, also regulates cell proliferation, lipid metabolism, and inflammation and is also touted as a tumor suppressor. Our focus on Nr1d1 was stimulated by data from a genome-wide search for mRNA correlates of cigarette smoke (CS) sensitive--whole smoke (WS) and filtered smoke (FS)--lung transcriptomes in tumor-resistant C57BL6 and tumor-susceptible AJ mice strains.

Modulation of ozone-sensitive genes in alpha-tocopherol transfer protein null mice.

Alpha-tocopherol transfer protein (ATTP) null mice (ATTP-/-) have a systemic alpha-tocopherol (AT) deficiency, with their lung AT levels being < 10% of those in AT-replete ATTP(+/+) mice when fed a standard rodent chow diet. ATTP(+/+) and ATTP(-/-) mice (4 wk old male mice, n = 16 per group) were fed a standard diet (35 IU AT/kg diet) for 8-12 wk, exposed 6 h/day for 3 days to either to O(3) (0.5 ppm) or filtered air, then sacrificed.

Sarcolipin and ubiquitin carboxy-terminal hydrolase 1 mRNAs are over-expressed in skeletal muscles of alpha-tocopherol deficient mice.

The transcriptome of ataxic muscles from alpha-tocopherol transfer protein deficient (ATTP-KO), 23-month old, mice was compared with that of their normal littermates. Genes encoding sarcolipin (sln) and ubiquitin carboxyl-terminal hydrolase (uchl1) were over-expressed (> or =10-fold) in ataxic muscles. SLN is a 3.

Effects of dietary carotenoids on mouse lung genomic profiles and their modulatory effects on short-term cigarette smoke exposures.

Male C57BL/6 mice were fed diets supplemented with either beta-carotene (BC) or lycopene (LY) that were formulated for human consumption. Four weeks of dietary supplementations results in plasma and lung carotenoid (CAR) concentrations that approximated the levels detected in humans. Bioactivity of the CARs was determined by assaying their effects on the activity of the lung transcriptome (~8,500 mRNAs).

A dose-response study on the effects of purified lycopene supplementation on biomarkers of oxidative stress.

Objective: While tomato product supplementation, containing antioxidant carotenoids, including lycopene, decreases oxidative stress, the role of purified lycopene as an antioxidant remains unclear. Thus, we tested the effects of different doses of purified lycopene supplementation on biomarkers of oxidative stress in healthy volunteers.

Methods: This was a double-blind, randomized, placebo-controlled trial, examining the effects of 8-week supplementation of purified lycopene, on plasma lycopene levels, biomarkers of lipid peroxidation {LDL oxidizability, malondialdehyde & hydroxynonenals (MDA & HNE), urinary F(2)-isoprostanes}, and markers of DNA damage in urine and lymphocytes.