The Effects of a Grape Seed Procyanidin Extract on Cytochrome P450 3A4 Activity and Inflammatory Mediators in the Lungs of Heavy Active and Former Smokers.

Grape seed procyanidin extract (GSE) is widely used to promote cardiovascular health and has purported anti-inflammatory properties. Chronic inflammation in the lungs caused by environmental toxins such as tobacco smoking plays a pivotal role in lung cancer development. In a modified phase I lung cancer chemoprevention study conducted in heavy active and former smokers using leucoselect phytosome (LP), a standardized grape seed procyanidin extract complexed with soy phospholipids to enhance bioavailability, three months of LP treatment favorably modulated a variety of surrogate endpoint biomarkers, including markers of cell proliferation.

Polygenic risk scores for autoimmune related diseases are significantly different in cancer exceptional responders.

A small number of cancer patients respond exceptionally well to therapies and survive significantly longer than patients with similar diagnoses. Profiling the germline genetic backgrounds of exceptional responder (ER) patients, with extreme survival times, can yield insights into the germline polymorphisms that influence response to therapy. As ERs showed a high incidence in autoimmune diseases, we hypothesized the differences in autoimmune disease risk could reflect the immune background of ERs and contribute to better cancer treatment responses.

Combinations of grape seed procyanidin extract and milk thistle silymarin extract against lung cancer - The role of MiR-663a and FHIT.

Aims: Grape seed procyanidin extract (GSE), and milk thistle silymarin extract (MTE) contain structurally distinct polyphenols, and each agent has been shown to exert antineoplastic effects against lung cancer. We hypothesize that combinations of GSE and MTE will additively enhance their anticancer effects against lung cancer.

Materials And Methods: The anti-proliferative effects of GSE, MTE and combinations were evaluated in lung neoplastic cell lines.

Effect of vaccination on the case fatality rate for COVID-19 infections 2020-2021: multivariate modelling of data from the US Department of Veterans Affairs.

Objectives: To evaluate the benefits of vaccination on the case fatality rate (CFR) for COVID-19 infections.

Design, Setting And Participants: The US Department of Veterans Affairs has 130 medical centres. We created multivariate models from these data-339 772 patients with COVID-19-as of 30 September 2021.

A novel method for handling pre-existing conditions in multivariate prediction model development for COVID-19 death in the Department of Veterans Affairs.

Many mathematical models have been proposed to predict death following the Coronavirus Disease 2019 (COVID-19); all started with comorbidity subsets for this still-little understood disease. Thus, we derived a novel predicted probability of death model (PDeathDx) upon all diagnostic codes documented in the Department of Veterans Affairs. We present the conceptual underpinnings and analytic approach in estimating the independent contribution of pre-existing conditions.

Potential for repurposing oral hypertension/diabetes drugs to decrease asthma risk in obesity.

Objective: Risk for asthma in the overweight/obese may be mediated by adiponectin and peroxisome proliferator activated receptor pathways and may be reduced by the use of oral drugs impacting these pathways, such as angiotensin converting enzyme inhibitors (ACE-I), thiazolidinediones (TZD), and angiotensin receptor blockers (ARB). Our study objective was to determine whether ACE-I, TZD, and/or ARB use in overweight/obese adults with diabetes mellitus and/or hypertension is associated with a lower risk for incident asthma.

Methods: Using an existing cohort of American veterans, we performed a longitudinal data analysis over 15 years.

Leucoselect Phytosome Modulates Serum Eicosapentaenoic Acid, Docosahexaenoic Acid, and Prostaglandin E3 in a Phase I Lung Cancer Chemoprevention Study.

Grape seed procyanidin extract (GSE) has been shown to exert antineoplastic properties in preclinical studies. Recently, we reported findings from a modified phase I, open-label, dose escalation clinical study conducted to evaluate the safety, tolerability, MTD, and potential chemopreventive effects of leucoselect phytosome, a standardized GSE complexed with soy phospholipids to enhance bioavailability, in heavy active and former smokers. Three months of leucoselect phytosome treatment significantly decreased bronchial Ki-67 labeling index (LI), a marker of cell proliferation on the bronchial epithelium.

A Pilot Study of a Grape Seed Procyanidin Extract for Lung Cancer Chemoprevention.

Grape seed procyanidin extract (GSE) had been reported to exert antineoplastic properties in preclinical studies. A modified phase I, open-label, dose-escalation clinical study was conducted to evaluate the safety, tolerability, MTD, and potential chemopreventive effects of leucoselect phytosome (LP), a standardized GSE complexed with soy phospholipids to enhance bioavailability, in heavy active and former smokers. Eight subjects ages 46-68 years were enrolled into the study and treated with escalating oral doses of LP for 3 months.

Malignant Middle Cerebral Artery Infarction Due to Hyponatremia Following Traumatic Brain Injury: A Case Report.

BACKGROUND Development of syndrome of inappropriate antidiuretic hormone secretion or cerebral salt wasting has been commonly noted in post-traumatic brain injury, and this condition may lead to hyponatremia resulting in cerebral edema and possible cerebral herniation. However, the predominant topographic pattern of edema from hyponatremia has not been well documented. Unlike numerous reports on hyponatremia and vasospasm following aneurysmal subarachnoid hemorrhage, the data for traumatic brain injury patient are still limited.

Grape seed procyanidin extract against lung cancer: the role of microrna-106b, bioavailability, and bioactivity.

MiR-106b is an oncomir and a potential target for anti-cancer therapy. We hypothesize that grape seed procyanidin extract (GSE) exerts antineoplastic effects on lung cancer through modulations of miR-106b and its downstream target. We found that GSE significantly down-regulated miR-106b in a variety of lung neoplastic cells and increased cyclin-dependent kinase inhibitor 1A () mRNA and protein (p21) levels.

A Randomized Phase IIb Trial of myo-Inositol in Smokers with Bronchial Dysplasia.

Previous preclinical studies and a phase I clinical trial suggested that myo-inositol may be a safe and effective lung cancer chemopreventive agent. We conducted a randomized, double blind, placebo-controlled phase IIb study to determine the chemopreventive effects of myo-inositol in smokers with bronchial dysplasia. Smokers with ≥1 site of dysplasia identified by autofluorescence bronchoscopy-directed biopsy were randomly assigned to receive oral placebo or myo-inositol, 9 g once a day for 2 weeks, and then twice a day for 6 months.

Grape Seed Procyanidin Extract Mediates Antineoplastic Effects against Lung Cancer via Modulations of Prostacyclin and 15-HETE Eicosanoid Pathways.

Grape seed procyanidin extract (GSE) has been reported to exert antineoplastic properties via the inhibition of cyclooxygenase-2 (COX-2)/prostaglandin E (PGE) eicosanoid pathways. In addition, ample data link carcinogenesis to inflammatory events involving other major eicosanoid metabolic pathways, including prostacyclin (PGI) and 15-hydroxyeicosatetraenoic acid (15-HETE). We therefore evaluated the effects of GSE on prostacyclin synthase (PTGIS)/PGI and 15-lipoxigenase-2 (15-LOX-2)/15-HETE productions by human lung premalignant and malignant cells and correlated the findings with antiproliferative or proapoptotic effects of GSE.

MicroRNA-19a/b mediates grape seed procyanidin extract-induced anti-neoplastic effects against lung cancer.

Oncomirs are microRNAs (miRNA) associated with carcinogenesis and malignant transformation. They have emerged as potential molecular targets for anti-cancer therapy. We hypothesize that grape seed procyanidin extract (GSE) exerts antineoplastic effects through modulations of oncomirs and their downstream targets.

Whole exome sequencing identifies novel candidate genes that modify chronic obstructive pulmonary disease susceptibility.

Background: Chronic obstructive pulmonary disease (COPD) is characterized by an irreversible airflow limitation in response to inhalation of noxious stimuli, such as cigarette smoke. However, only 15-20 % smokers manifest COPD, suggesting a role for genetic predisposition. Although genome-wide association studies have identified common genetic variants that are associated with susceptibility to COPD, effect sizes of the identified variants are modest, as is the total heritability accounted for by these variants.

Spectrum of Clonal Large Granular Lymphocytes (LGLs) of αβ T Cells: T-Cell Clones of Undetermined Significance, T-Cell LGL Leukemias, and T-Cell Immunoclones.

Objectives: Clones of T-cell large granular lymphocytes (LGLTs) were detected by flow cytometry. Disease associations are described.

Methods: Flow cytometry on blood or marrow detected clonal LGLTs by analyzing variable regions of the T-cell receptor β chain.

Abnormal immunophenotype of the T-cell-receptor beta Chain in follicular-helper T cells of angioimmunoblastic T-cell lymphoma.

Objective: Analysis for 24 variable regions of the T-cell-receptor beta chain by flow cytometry (Vbeta) is a new technique to detect clonal alpha-beta T lymphocytes and is characteristically performed on peripheral blood. Angioimmunoblastic T-cell lymphoma (AITL) has increased neoplastic follicular-helper T cells (FHT), which often express CD10; but nonneoplastic, CD10-positive T cells may be associated with reactive lymphadenopathy and with B-cell lymphomas. This study documents the utility of Vbeta analysis of FHT in specimens of AITL from blood, from marrow, and from lymph nodes.

Polymorphisms of peroxisome proliferator-activated receptors and survival of lung cancer and upper aero-digestive tract cancers.

Background: Peroxisome proliferator-activated receptors (PPARs) are transcriptional factors involved in several biological processes such as inflammation, cancer growth, progression and apoptosis that are important in lung and upper aero-digestive tract (UADT) cancer outcomes. Nonetheless, there are no published studies of the relationship between PPARs gene polymorphisms and survival of patients with lung cancer or UADT cancers.

Methods: 1212 cancer patients (611 lung, 303 oral, 100 pharyngeal, 90 laryngeal, and 108 esophageal) were followed for a median duration of 11 years.

Tobacco smoking, NBS1 polymorphisms, and survival in lung and upper aerodigestive tract cancers with semi-Bayes adjustment for hazard ratio variation.

Purpose: Although single nucleotide polymorphisms (SNPs) of NBS1 have been associated with susceptibility to lung and upper aerodigestive tract (UADT) cancers, their relations to cancer survival and measures of effect are largely unknown.

Methods: Using follow-up data from 611 lung cancer cases and 601 UADT cancer cases from a population-based case-control study in Los Angeles, we prospectively evaluated associations of tobacco smoking and 5 NBS1 SNPs with all-cause mortality. Mortality data were obtained from the Social Security Death Index.

Chemoprevention of lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.

Background: Lung cancer is the most common cause of cancer death in men and women in the United States. Cigarette smoking is the main risk factor. Former smokers are at a substantially increased risk of developing lung cancer compared with lifetime never smokers.

Green tea inhibits cycolooxygenase-2 in non-small cell lung cancer cells through the induction of Annexin-1.

Elevated cyclooygenase-2 (COX-2) expression is frequently observed in human non-small cell lung cancer (NSCLC) and associated with poor prognosis, indicating critical involvement of the inflammatory pathway in lung carcinogenesis. Recently, we found that green tea extract (GTE) induced Annexin-1 (ANX1) in the lung adenocarcinoma A549 cells. ANX1 is a glucocorticoid-inducible 37kDa protein involved in a wide range biological function and is an important anti-inflammatory mediator.

Body mass index change in adulthood and lung and upper aerodigestive tract cancers.

Body mass index (BMI) has been inversely associated with lung and upper aerodigestive tract (UADT) cancers. However, only a few studies have assessed BMI change in adulthood in relation to cancer. To understand the relationship between BMI change and these cancers in both men and women, we analyzed data from a population-based case-control study conducted in Los Angeles County.

Lung cancer chemoprevention with celecoxib in former smokers.

Ample studies suggest that the cyclooxygenase-2 (COX-2)/prostaglandin E(2) (PGE(2)) pathway plays a pivotal role in carcinogenesis and that COX-2 inhibition may help prevent lung cancer. Therefore, we conducted a randomized, double-blind, placebo-controlled trial of the COX-2-selective inhibitor celecoxib (400 mg bid for 6 months) in former-smokers (age ≥ 45, ≥ 30 pack-years of smoking, ≥ 1 year of sustained abstinence from smoking). We assessed the impact of celecoxib on cellular and molecular events associated with lung cancer pathogenesis; the primary endpoint was bronchial Ki-67 labeling index (Ki-67 LI) after 6 months of treatment.

Elevated levels of CXC chemokine connective tissue activating peptide (CTAP)-III in lung cancer patients.

Despite advances in treatments, lung cancer has been the leading cause of cancer-related deaths in the United States for the past several decades. Recent findings from the National Lung Screening Trial reveal that low-dose helical computed tomography (CT) scan screening of high-risk individuals reduces lung cancer mortality. This suggests that early detection is of key importance to improving patient outcome.

Oral iloprost improves endobronchial dysplasia in former smokers.

There are no established chemopreventive agents for lung cancer, the leading cause of cancer death in the United States. Prostacyclin levels are low in lung cancer and supplementation prevents lung cancer in preclinical models. We carried out a multicenter double-blind, randomized, phase II placebo-controlled trial of oral iloprost in current or former smokers with sputum cytologic atypia or endobronchial dysplasia.