Intraductal Transplantation Models of Human Pancreatic Ductal Adenocarcinoma Reveal Progressive Transition of Molecular Subtypes.

Pancreatic ductal adenocarcinoma (PDAC) is the most lethal common malignancy, with little improvement in patient outcomes over the past decades. Recently, subtypes of pancreatic cancer with different prognoses have been elaborated; however, the inability to model these subtypes has precluded mechanistic investigation of their origins. Here, we present a xenotransplantation model of PDAC in which neoplasms originate from patient-derived organoids injected directly into murine pancreatic ducts.

SOAT1 promotes mevalonate pathway dependency in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis, and new therapies are needed. Altered metabolism is a cancer vulnerability, and several metabolic pathways have been shown to promote PDAC. However, the changes in cholesterol metabolism and their role during PDAC progression remain largely unknown.

Identification of Resistance Pathways Specific to Malignancy Using Organoid Models of Pancreatic Cancer.

Purpose: is mutated in the majority of pancreatic ductal adenocarcinoma. MAPK and PI3K-AKT are primary KRAS effector pathways, but combined MAPK and PI3K inhibition has not been demonstrated to be clinically effective to date. We explore the resistance mechanisms uniquely employed by malignant cells.

Organoid models for translational pancreatic cancer research.

Despite recent advances in the treatment of cancer, pancreatic ductal adenocarcinoma (PDAC) still retains the worst survival rate of common malignancies. Late diagnosis and lack of curative therapeutic options are the most pressing clinical problems for this disease. Therefore, there is a need for patient models and biomarkers that can be applied in the clinic to identify the most effective therapy for a patient.

Generation and Culture of Tumor and Metastatic Organoids from Murine Models of Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDA) is a lethal malignancy that is refractory to all current therapies. Research into the mechanisms driving this cancer is the key to developing better diagnostic and treatment options which are urgently needed in the clinic. Genetically engineered mouse models of PDA have been valuable research tools, enabling studies of all stages of PDA progression.

Generation and Culture of Human Pancreatic Ductal Adenocarcinoma Organoids from Resected Tumor Specimens.

The recent development of human organoids as patient-specific models of pancreatic ductal adenocarcinoma (PDA) has helped set the stage for a new era of personalized medicine. Organoids can be generated from a resected PDA tumor in as little as 2-4 weeks, and are amenable to therapeutic screening as well as genetic and biochemical perturbation. Moreover, because these models promote the propagation of the neoplastic PDA cells at the expense of the stromal cells, transcriptome and genome-wide sequencing of organoids offers an unprecedented view of the genetic and expression changes occurring in the neoplastic cells of individual tumors.

Testing Susceptibility of Patient-Derived Organoid Cultures to Therapies: Pharmacotyping.

Increasingly, patient models of disease are being utilized to facilitate precision medicine approaches through molecular characterization or direct chemotherapeutic testing. Organoids, 3-dimensional (3D) cultures of neoplastic cells derived from primary tumor specimens, represent an ideal platform for these types of studies because benchtop protocols previously developed for 2-dimensional cell lines can be adapted for use. These protocols include directly testing the survival of these organoid cultures when exposed to clinically relevant chemotherapeutic agents, a process we have called pharmacotyping.

Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer.

Pancreatic stellate cells (PSCs) differentiate into cancer-associated fibroblasts (CAFs) that produce desmoplastic stroma, thereby modulating disease progression and therapeutic response in pancreatic ductal adenocarcinoma (PDA). However, it is unknown whether CAFs uniformly carry out these tasks or if subtypes of CAFs with distinct phenotypes in PDA exist. We identified a CAF subpopulation with elevated expression of α-smooth muscle actin (αSMA) located immediately adjacent to neoplastic cells in mouse and human PDA tissue.

Model organoids provide new research opportunities for ductal pancreatic cancer.

We recently established organoid models from normal and neoplastic murine and human pancreas tissues. These organoids exhibit ductal- and disease stage-specific characteristics and, after orthotopic transplantation, recapitulate the full spectrum of tumor progression. Pancreatic organoid technology provides a novel platform for the study of tumor biology and the discovery of potential biomarkers, therapeutics, and personalized medicine strategies.

Modeling pancreatic cancer with organoids.

Pancreatic ductal adenocarcinoma (PDA) is a highly lethal malignancy for which new treatment and diagnostic approaches are urgently needed. In order for such breakthroughs to be discovered, researchers require systems that accurately model the development and biology of PDA. While cell lines, genetically engineered murine models, and xenografts have all led to valuable clinical insights, organotypic culture models have emerged as tractable systems to recapitulate the complex three-dimensional organization of PDA.

Organoid models of human and mouse ductal pancreatic cancer.

Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and human pancreas tissues.

The material convoy after age 50.

Objectives: Possessions constitute a dynamic "material convoy" that accumulates across adulthood to furnish role enactments and the development of the self. Following a familiar life course arc, older people should hypothetically release the possessions that equipped the daily lives that they no longer have.

Method: We use new survey data on possession divestment from the 2010 Health and Retirement Study to assess activity on behalf of the material convoy after age 50.

Oral health problems and mortality.

Background/purpose: Previous studies have shown the relationship between individual oral health conditions and mortality; however, the relationship between mortality and multiple oral health conditions has not been examined. This study investigates the link between individual oral health problems and oral comorbidity and mortality risk.

Materials And Methods: Data are derived from the National Health and Nutrition Examination Survey 1999-2004, which is linked to the National Death Index for mortality follow-up through 2006.

The yeast Snt2 protein coordinates the transcriptional response to hydrogen peroxide-mediated oxidative stress.

Regulation of gene expression is a vital part of the cellular stress response, yet the full set of proteins that orchestrate this regulation remains unknown. Snt2 is a Saccharomyces cerevisiae protein whose function has not been well characterized that was recently shown to associate with Ecm5 and the Rpd3 deacetylase. Here, we confirm that Snt2, Ecm5, and Rpd3 physically associate.

Prevalence of oral health problems in U.S. adults, NHANES 1999-2004: exploring differences by age, education, and race/ethnicity.

Using the National Health and Nutrition Examination Surveys (NHANES) 1999-2004, the authors examined age patterns in oral health indicators by race/ethnicity and socioeconomic status related to edentulism, presence of root caries, and periodontal disease. Our analysis included subjects who were non-Hispanic White, Mexican American, and African American over the age of 20, and who participated in the NHANES oral health examination. African Americans experienced more oral health problems at younger ages; as age increased, so did racial disparities in oral health problems.

Poverty and Material Hardship in Grandparent-Headed Households.

Using the 2001 Survey of Income and Program Participation, the current study examines poverty and material hardship among children living in 3-generation (n = 486), skipped-generation (n = 238), single-parent (n = 2,076), and 2-parent (n = 6,061) households. Multinomial and logistic regression models indicated that children living in grandparent-headed households experience elevated risk of health insecurity (as measured by receipt of public insurance and uninsurance)-a disproportionate risk given rates of poverty within those households. Children living with single parents did not share this substantial risk.

Who are the Latino baby boomers? Demographic and economic characteristics of a hidden population.

The United States is confronting two simultaneous demographic shifts with profound implications for public policy: population aging and increasing diversity. These changes are accelerating during a dramatic economic downturn, placing entitlement reform prominently on the national policy agenda. Using decennial census data from 2000, this paper examines the nexus of these trends by examining characteristics of Latino baby boomers.

The Implications of Grandparent Coresidence for Economic Hardship among Children in Mother-Only Families.

Estimates suggest that more than 6 million children live with at least one grandparent. Despite evidence establishing the growing prevalence of this arrangement, limited research has focused on estimating the implications of co-residence for the economic well-being of grandchildren. Using data from the 2001 panel of the Survey of Income and Program Participation, this paper examines levels of financial hardship among a particularly vulnerable group of children - those living in mother-only families.

Preventive health behaviors among grandmothers raising grandchildren.

Objectives: We examined differential preventive health behavior among grandmothers who recently began raising a grandchild, grandmothers raising a grandchild for at least 2 years, and grandmothers not raising a grandchild.

Methods: Data came from the 2000, 2002, and 2004 waves of the Health and Retirement Study. We ran multivariate logistic regression models to assess receipt of influenza vaccination, cholesterol screening, monthly breast self-exam, mammography, and Papanicolaou (Pap) tests among grandmothers aged 50 to 75.

Depressive Symptoms Among Grandparents Raising Grandchildren: The Impact of Participation in Multiple Roles.

Using the Health and Retirement Study, this research examines well-being among grandparents raising grandchildren during middle to late life, specifically looking at how other roles in which a grandparent is participating (such as worker, volunteer, parent or caregiver) may influence depressive symptoms among grandparent caregivers. Results indicate that grandparents who have recently begun raising a grandchild experience lower levels of well-being when compared to grandparents who are not raising a grandchild regardless of the grandparent's level of participation in roles beyond that of grandparent caregiver, while grandparents who have been raising a grandchild for longer periods of time seem to benefit from their participation in multiple roles. However, a higher level of participation in outside roles is associated with a decline in well-being among grandparents who stopped raising a grandchild, suggesting that, for these grandparents, participation in multiple roles acted mainly as a stressor, rather than as a resource.

PHD fingers in human diseases: disorders arising from misinterpreting epigenetic marks.

Histone covalent modifications regulate many, if not all, DNA-templated processes, including gene expression and DNA damage response. The biological consequences of histone modifications are mediated partially by evolutionarily conserved "reader/effector" modules that bind to histone marks in a modification- and context-specific fashion and subsequently enact chromatin changes or recruit other proteins to do so. Recently, the Plant Homeodomain (PHD) finger has emerged as a class of specialized "reader" modules that, in some instances, recognize the methylation status of histone lysine residues, such as histone H3 lysine 4 (H3K4).

Grandparents Raising Grandchildren in the United States: Changing Family Forms, Stagnant Social Policies.

As a consequence of increased divorce rates, the proliferation of single-parent families, and patterns of economic stagnation, parents are increasingly relying on extended family to care for children. In the past few decades, a substantial increase in the number of grandparents raising grandchildren has been observed within the United States. Grandparents who raise their grandchildren are particularly vulnerable, as are the grandchildren in their care; however, U.