Novel metabolomic predictors of incident colorectal cancer in men and women.

Background: Metabolomic profiles may influence colorectal cancer (CRC) development. Few studies have performed pre-diagnostic metabolome-wide analyses with CRC risk.

Methods: We conducted a nested case-control study among women (Nurses' Health Study (NHS)) and men (Health Professionals Follow-up Study (HPFS)) who provided blood between 1989 and 1995.

Antipsychotics possess anti-glioblastoma activity by disrupting lysosomal function and inhibiting oncogenic signaling by stabilizing PTEN.

The repurposing of medications developed for central nervous system (CNS) disorders, possessing favorable safety profiles and blood-brain barrier permeability, represents a promising strategy for identifying new therapies to combat glioblastoma (GBM). In this study, we investigated the anti-GBM activity of specific antipsychotics and antidepressants in vitro and in vivo. Our results demonstrate that these compounds share a common mechanism of action in GBM, disrupting lysosomal function and subsequently inducing lysosomal membrane rupture and cell death.

The evaluation and analysis of irritable bowel syndrome-related short videos on social media (TikTok).

Background: TikTok is one of the fastest growing social media platforms. Irritable bowel syndrome (IBS) has recently become a trending topic of interest among TikTok users.

Aim: To better understand the quality and accuracy of information presented in the most popular IBS-relevant videos on TikTok.

High-quality fruit and vegetable characterized by cardiometabolic biomarkers and its relation to major chronic disease risk: results from 3 prospective United States cohort studies.

Background: The current guidelines recommend a specified total serving of fruits and vegetables (FV). However, how differences in their nutritional quality of specific FV influence overall health remains unclear.

Objectives: To identify high-quality FV using 14 cardiometabolic biomarkers, and assess their consumption, alongside overall FV intake, with chronic disease risk.

Identifying modifiable risk factors to prevent aggressive colorectal cancer.

It remains unclear if pre-diagnostic factors influence the developmental pathways of colorectal cancer (CRC) that could enhance tumor aggressiveness. This study used prospective data from 205,489 cancer-free US health professionals to investigate the associations of 31 known or putative risk factors with the risk of aggressive CRC. Tumor aggressiveness was characterized by three endpoints: aggressive CRC (cancer that causes death within 5 years of diagnosis), fatal CRC, and tumor stage at diagnosis.

Metabolomic signatures of inflammation and metabolic dysregulation in relation to colorectal cancer risk.

Background: Inflammation and metabolic dysregulation are associated with increased risk of colorectal cancer (CRC); the underlying mechanisms are not fully understood. We characterized metabolomic signatures of inflammation and metabolic dysregulation and evaluated the association of the signatures and individual metabolites with CRC risk.

Methods: Among 684 incident CRC cases and 684 age-matched controls in the Nurses' Health Study (n = 818 women) and Health Professionals Follow-up Study (n = 550 men), we applied reduced rank and elastic net regression to 277 metabolites for markers of inflammation (C-reactive protein, interleukin 6, tumor necrosis factor receptor superfamily member 1B, and growth differentiation factor 15) or metabolic dysregulation (body mass index, waist circumference, C-peptide, and adiponectin) to derive metabolomic signatures.

Healthy dietary patterns and risk of prostate cancer in men at high genetic risk.

Prostate cancer has high heritability. Healthy lifestyle has been associated with lower lethal prostate cancer risk among men at increased genetic susceptibility, but the role of healthy dietary patterns remains unknown. We prospectively followed 10,269 genotyped men in the Health Professionals Follow-up Study (1993-2019).

miRNA-194-3p represses NF-κB in gliomas to attenuate iPSC genes and proneural to mesenchymal transition.

Severe tumor heterogeneity drives the aggressive and treatment refractory nature of glioblastomas (GBMs). While limiting GBM heterogeneity offers promising therapeutic potential, the underlying mechanisms that regulate GBM plasticity remain poorly understood. We utilized 14 patient-derived and four commercially available cell lines to uncover miR-194-3p as a key epigenetic determinant of stemness and transcriptional subtype in GBM.

Presumed Pathogenic Germ Line and Somatic Variants in African American Thyroid Cancer.

African American (AA) thyroid cancer patients have worse prognoses than European Americans (EA), which has been attributed to both health care disparities and possible genetic differences. We investigated the impact of both germ line and somatic variants on clinical outcome in a cohort of AA nonmedullary thyroid cancer (NMTC) patients who had received therapeutic intervention from cancer centers. Whole-exome sequencing was performed on DNA from available blood/normal tissues ( = 37) and paired tumor samples ( = 32) collected from 37 and 29 AA NMTC patients, respectively.

Combined Vorinostat and Chloroquine Inhibit Sodium-Iodide Symporter Endocytosis and Enhance Radionuclide Uptake In Vivo.

Purpose: Patients with aggressive thyroid cancer are frequently failed by the central therapy of ablative radioiodide (RAI) uptake, due to reduced plasma membrane (PM) localization of the sodium/iodide symporter (NIS). We aimed to understand how NIS is endocytosed away from the PM of human thyroid cancer cells, and whether this was druggable in vivo.

Experimental Design: Informed by analysis of endocytic gene expression in patients with aggressive thyroid cancer, we used mutagenesis, NanoBiT interaction assays, cell surface biotinylation assays, RAI uptake, and NanoBRET to understand the mechanisms of NIS endocytosis in transformed cell lines and patient-derived human primary thyroid cells.

Association of dietary insulinemic and inflammatory potential with risk of liver cancer and chronic liver disease mortality in postmenopausal women: a prospective cohort study.

Background: Low diet quality, diabetes, and chronic inflammation are risk factors of liver cancer and chronic liver disease (CLD), but the extent to which insulinemic and inflammatory diets are independently associated with risk of liver cancer and CLD mortality is unknown.

Methods: We conducted a prospective cohort analysis among 78,356 postmenopausal women in the Women's Health Initiative Observational Study. Two validated dietary indices, the empirical dietary index for hyperinsulinemia (EDIH) and the empirical dietary inflammation pattern (EDIP), were estimated from a food-frequency questionnaire.

The Metastasis Suppressor Is Hypermethylated at Intron 1 in Thyroid Cancer.

Regulator of calcineurin 1.4 (RCAN1.4) is a functionally downregulated metastasis progression suppressor (MPS) in thyroid cancer; however, the mechanisms for RCAN1.

Dietary inflammatory and insulinemic potential, risk of hepatocellular carcinoma, and chronic liver disease mortality.

Background: Diet modulates inflammation and insulin response and may be an important modifiable factor in the primary prevention of hepatocellular carcinoma (HCC) and chronic liver disease (CLD). We developed the empirical dietary inflammatory pattern (EDIP) and empirical dietary index for hyperinsulinemia (EDIH) scores to assess the inflammatory and insulinemic potentials of diet. We prospectively examined the associations of EDIP and EDIH at baseline with the following HCC risk and CLD mortality.

Optimal dietary patterns for prevention of chronic disease.

Multiple dietary patterns have been associated with different diseases; however, their comparability to improve overall health has yet to be determined. Here, in 205,852 healthcare professionals from three US cohorts followed for up to 32 years, we prospectively assessed two mechanism-based diets and six diets based on dietary recommendations in relation to major chronic disease, defined as a composite outcome of incident major cardiovascular disease (CVD), type 2 diabetes and cancer. We demonstrated that adherence to a healthy diet was generally associated with a lower risk of major chronic disease (hazard ratio (HR) comparing the 90th with the 10th percentile of dietary pattern scores = 0.

Healthy Eating Patterns and Risk of Total and Cause-Specific Mortality.

Importance: The current Dietary Guidelines for Americans recommend multiple healthy eating patterns. However, few studies have examined the associations of adherence to different dietary patterns with long-term risk of total and cause-specific mortality.

Objective: To examine the associations of dietary scores for 4 healthy eating patterns with risk of total and cause-specific mortality.

Association between dietary inflammatory potential and mortality after cancer diagnosis in the Women's Health Initiative.

Background: Chronic inflammation is implicated in cancer prognosis and can be modulated by diet. We examined associations between post-diagnosis dietary inflammatory potential and mortality outcomes among post-menopausal women diagnosed with cancer in the Women's Health Initiative (WHI).

Methods: Energy-adjusted dietary inflammatory index scores (E-DII) were calculated from dietary and supplemental intake data collected on the first food frequency questionnaire following the diagnosis of primary invasive cancer for 3434 women in the WHI.

Prognostic role of inflammatory diets in colorectal cancer overall and in strata of tumor-infiltrating lymphocyte levels.

Background: Certain dietary patterns can elicit systemic and intestinal inflammatory responses, which may influence adaptive anti-tumor immune responses and tumor behavior. We hypothesized that pro-inflammatory diets might be associated with higher colorectal cancer mortality and that the association might be stronger for tumors with lower immune responses.

Methods: We calculated an empirical dietary inflammatory pattern (EDIP) score in 2829 patients among 3988 incident rectal and colon carcinoma cases in the Nurses' Health Study and Health Professionals Follow-up Study.

Long-term Weight Training and Mortality in U.S. Male Health Professionals With and Without Type 2 Diabetes.

Objective: To investigate the relationship between long-term weight training and mortality in male health professionals with and without type 2 diabetes.

Research Design And Methods: We analyzed 31,140 men without type 2 diabetes and 2,588 with type 2 diabetes from the Health Professionals Follow-up Study (1992-2018). Information on weight training was repeatedly assessed using a biennial questionnaire.

Long-Term Leisure-Time Physical Activity Intensity and All-Cause and Cause-Specific Mortality: A Prospective Cohort of US Adults.

Background: The 2018 physical activity guidelines for Americans recommend a minimum of 150 to 300 min/wk of moderate physical activity (MPA), 75 to 150 min/wk of vigorous physical activity (VPA), or an equivalent combination of both. However, it remains unclear whether higher levels of long-term VPA and MPA are, independently and jointly, associated with lower mortality.

Methods: A total of 116 221 adults from 2 large prospective US cohorts (Nurses' Health Study and Health Professionals Follow-up Study, 1988-2018) were analyzed.

Postdiagnostic Inflammatory, Hyperinsulinemic, and Insulin-Resistant Diets and Lifestyles and the Risk of Prostate Cancer Progression and Mortality.

Background: Inflammatory and insulin pathways have been linked to prostate cancer; postdiagnostic behaviors activating these pathways may lead to poor outcomes. The empirical dietary inflammatory pattern (EDIP), empirical dietary index for hyperinsulinemia (EDIH), and empirical dietary index for insulin resistance (EDIR), and associated lifestyle indices (ELIH, ELIR) predict biomarkers of inflammation (EDIP: IL6, TNFaR2, CRP) and insulin secretion (EDIH/ELIH: c-peptide; EDIR/ELIR: TAG:HDL) from whole foods and behaviors.

Methods: Associations of these indices with time to prostate cancer progression (primary, n = 2,056) and prostate cancer-specific mortality (PCSM; secondary, n = 2,447) were estimated among men diagnosed with nonmetastatic prostate cancer in the Cancer of the Prostate Strategic Urologic Research Endeavor cohort diet and lifestyle sub-study.

Pre-diagnosis and post-diagnosis dietary patterns and survival in women with ovarian cancer.

Background: Evidence is limited on inflammation-related dietary patterns and mortality in ovarian cancer survivors.

Methods: We examined the associations between pre- and post-diagnosis dietary patterns, including change in diet from before to after diagnosis, and mortality among 1003 ovarian cancer survivors in two prospective cohort studies. Dietary pattern scores for empirical dietary inflammatory pattern (EDIP) and Alternative Healthy Eating Index (AHEI) were calculated based on food frequency questionnaires.