DNA replication in primary hepatocytes without the six-subunit ORC.

The six subunit ORC is essential for initiation of DNA replication in eukaryotes. Cancer cell-lines in culture can survive and replicate DNA replication after genetic inactivation of individual ORC subunits, ORC1, ORC2 or ORC5. In primary cells, ORC1 was dispensable in the mouse liver for endo-reduplication, but this could be explained by the ORC1 homolog, CDC6, substituting for ORC1 to restore functional ORC.

Balloon assisted Woven endobridge deployment (BAWD): A safety and efficacy study.

Background: Balloon-assisted deployment/remodelling is a proven adjunctive technique for coil embolization of intracranial aneurysms, and it may be a helpful adjunct in delivering the Woven EndoBridge (WEB) device.

Objective: To evaluate the safety, efficacy and feasibility of balloon-assisted WEB deployment in both ruptured and unruptured intracranial aneurysms in both typical and atypical locations.

Methods: Patients who underwent treatment of ruptured and unruptured intracranial aneurysms with the BAWD technique were retrospectively identified from a prospectively maintained database at two neurointerventional centres.

The splanchnic mesenchyme is the tissue of origin for pancreatic fibroblasts during homeostasis and tumorigenesis.

Pancreatic cancer is characterized by abundant desmoplasia, a dense stroma composed of extra-cellular and cellular components, with cancer associated fibroblasts (CAFs) being the major cellular component. However, the tissue(s) of origin for CAFs remains controversial. Here we determine the tissue origin of pancreatic CAFs through comprehensive lineage tracing studies in mice.

Stromal p53 Regulates Breast Cancer Development, the Immune Landscape, and Survival in an Oncogene-Specific Manner.

Unlabelled: Coevolution of tumor cells and adjacent stromal elements is a key feature during tumor progression; however, the precise regulatory mechanisms during this process remain unknown. Here, we show stromal p53 loss enhances oncogenic KrasG12D, but not ErbB2, driven tumorigenesis in murine mammary epithelia. Stroma-specific p53 deletion increases both epithelial and fibroblast proliferation in mammary glands bearing the KrasG12D oncogene in epithelia, while concurrently increasing DNA damage and/or DNA replication stress and decreasing apoptosis in the tumor cells proper.

Diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) detection limits for blood on fabric: Orientation and coating uniformity effects.

Diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) was used to analyze four types of forensically relevant fabrics coated with varying dilutions of blood. The blood was applied in two manners, dip coating with a smooth and uniform layer and drip coating with droplets from pipettes. Spectra of neat and dip coated fabrics were acquired using controlled orientations, and these were compared to spectra collected on samples with random orientations.

Stromal Platelet-Derived Growth Factor Receptor-β Signaling Promotes Breast Cancer Metastasis in the Brain.

Platelet-derived growth factor receptor-beta (PDGFRβ) is a receptor tyrosine kinase found in cells of mesenchymal origin such as fibroblasts and pericytes. Activation of this receptor is dependent on paracrine ligand induction, and its preferred ligand PDGFB is released by neighboring epithelial and endothelial cells. While expression of both PDGFRβ and PDGFB has been noted in patient breast tumors for decades, how PDGFB-to-PDGFRβ tumor-stroma signaling mediates breast cancer initiation, progression, and metastasis remains unclear.

Abrupt involution induces inflammation, estrogenic signaling, and hyperplasia linking lack of breastfeeding with increased risk of breast cancer.

Background: A large collaborative analysis of data from 47 epidemiological studies concluded that longer duration of breastfeeding reduces the risk of developing breast cancer. Despite the strong epidemiological evidence, the molecular mechanisms linking prolonged breastfeeding to decreased risk of breast cancer remain poorly understood.

Methods: We modeled two types of breastfeeding behaviors in wild type FVB/N mice: (1) normal or gradual involution of breast tissue following prolonged breastfeeding and (2) forced or abrupt involution following short-term breastfeeding.

A sustainable method to reduce postoperative oxycodone discharge prescribing in a metropolitan tertiary referral hospital.

The primary objective of this quality improvement project was to measure and reduce the number of oxycodone immediate-release tablets dispensed to overnight stay surgical patients at discharge. The secondary objective was to reduce the proportion of inappropriate oxycodone immediate-release prescriptions at discharge. Interrupted time series analysis was performed in four surgical wards of St Vincent's Public Hospital, Sydney.

Stromal PTEN determines mammary epithelial response to radiotherapy.

The importance of the tumor-associated stroma in cancer progression is clear. However, it remains uncertain whether early events in the stroma are capable of initiating breast tumorigenesis. Here, we show that in the mammary glands of non-tumor bearing mice, stromal-specific phosphatase and tensin homolog (Pten) deletion invokes radiation-induced genomic instability in neighboring epithelium.

Stromal PTEN inhibits the expansion of mammary epithelial stem cells through Jagged-1.

This corrects the article DOI: 10.1038/onc.2016.

Stromal PTEN inhibits the expansion of mammary epithelial stem cells through Jagged-1.

Fibroblasts within the mammary tumor microenvironment are active participants in carcinogenesis mediating both tumor initiation and progression. Our group has previously demonstrated that genetic loss of phosphatase and tensin homolog (PTEN) in mammary fibroblasts induces an oncogenic secretome that remodels the extracellular milieu accelerating ErbB2-driven mammary tumor progression. While these prior studies highlighted a tumor suppressive role for stromal PTEN, how the adjacent normal epithelium transforms in response to PTEN loss was not previously addressed.

Viral oncogene expression in the stem/progenitor cell compartment of the mouse intestine induces adenomatous polyps.

Unlabelled: Genetic and epigenetic events that alter gene expression and/or protein function or localization are thought to be the primary mechanism that drives tumorigenesis and governs the clinical behavior of cancers. Yet, a number of studies have shown that the effects of oncogene expression or tumor suppressor ablation are highly dependent on cell type. The molecular basis for this cell-type specificity and how it contributes to tumorigenesis are unknown.

Selective roles of E2Fs for ErbB2- and Myc-mediated mammary tumorigenesis.

Previous studies have demonstrated that cyclin D1, an upstream regulator of the Rb/E2F pathway, is an essential component of the ErbB2/Ras (but not the Wnt/Myc) oncogenic pathway in the mammary epithelium. However, the role of specific E2fs for ErbB2/Ras-mediated mammary tumorigenesis remains unknown. Here, we show that in the majority of mouse and human primary mammary carcinomas with ErbB2/HER2 overexpression, E2f3a is up-regulated, raising the possibility that E2F3a is a critical effector of the ErbB2 oncogenic signaling pathway in the mammary gland.

Ets2 in tumor fibroblasts promotes angiogenesis in breast cancer.

Tumor fibroblasts are active partners in tumor progression, but the genes and pathways that mediate this collaboration are ill-defined. Previous work demonstrates that Ets2 function in stromal cells significantly contributes to breast tumor progression. Conditional mouse models were used to study the function of Ets2 in both mammary stromal fibroblasts and epithelial cells.

Evidence for a stepwise program of extrathymic T cell development within the human tonsil.

The development of a broad repertoire of T cells, which is essential for effective immune function, occurs in the thymus. Although some data suggest that T cell development can occur extrathymically, many researchers remain skeptical that extrathymic T cell development has an important role in generating the T cell repertoire in healthy individuals. However, it may be important in the setting of poor thymic function or congenital deficit and in the context of autoimmunity, cancer, or regenerative medicine.

Reprogramming of the tumour microenvironment by stromal PTEN-regulated miR-320.

PTEN (Phosphatase and tensin homolog deleted on chromosome 10) expression in stromal fibroblasts suppresses epithelial mammary tumours, but the underlying molecular mechanisms remain unknown. Using proteomic and expression profiling, we show that Pten loss from mammary stromal fibroblasts activates an oncogenic secretome that orchestrates the transcriptional reprogramming of other cell types in the microenvironment. Downregulation of miR-320 and upregulation of one of its direct targets, ETS2 (v-ets erythroblastosis virus E26 oncogene homolog 2) are critical events in Pten-deleted stromal fibroblasts responsible for inducing this oncogenic secretome, which in turn promotes tumour angiogenesis and tumour-cell invasion.

The Ras oncogene signals centrosome amplification in mammary epithelial cells through cyclin D1/Cdk4 and Nek2.

Centrosome amplification (CA) contributes to carcinogenesis by generating aneuploidy. Elevated frequencies of CA in most benign breast lesions and primary tumors suggest a causative role for CA in breast cancers. Clearly, identifying which and how altered signal transduction pathways contribute to CA is crucial to breast cancer control.

Pten in stromal fibroblasts suppresses mammary epithelial tumours.

The tumour stroma is believed to contribute to some of the most malignant characteristics of epithelial tumours. However, signalling between stromal and tumour cells is complex and remains poorly understood. Here we show that the genetic inactivation of Pten in stromal fibroblasts of mouse mammary glands accelerated the initiation, progression and malignant transformation of mammary epithelial tumours.

Targeted deletion of Prkar1a reveals a role for protein kinase A in mesenchymal-to-epithelial transition.

Dysregulation of protein kinase A (PKA) activity, caused by loss of function mutations in PRKAR1A, is known to induce tumor formation in the inherited tumor syndrome Carney complex (CNC) and is also associated with sporadic tumors of the thyroid and adrenal. We have previously shown that Prkar1a(+/-) mice develop schwannomas reminiscent of those seen in CNC and that similar tumors are observed in tissue-specific knockouts (KO) of Prkar1a targeted to the neural crest. Within these tumors, we have previously described the presence of epithelial islands, although the nature of these structures was unclear.

Direct evidence for epithelial-mesenchymal transitions in breast cancer.

We developed stromal- and epithelial-specific cre-transgenic mice to directly visualize epithelial-mesenchymal transition (EMT) during cancer progression in vivo. Using three different oncogene-driven mouse mammary tumor models and cell-fate mapping strategies, we show in vivo evidence for the existence of EMT in breast cancer and show that myc can specifically elicit this process. Hierarchical cluster analysis of genome-wide loss of heterozygosity reveals that the incidence of EMT in invasive human breast carcinomas is rare, but when it occurs it is associated with the amplification of MYC.

[Epidemiologic study about the variation of the demand in mental health in the last two decades].

We have investigated age, sex, nationality, origin, diagnosis and treatment types in ambulatory patients of the External Clinics of the Division Health Mental of the General Hospital for Acute Patients "Dr. Teodoro Alvarez", of 600 Clinical Histories obtained in the years 1980, 1990 and 2000. These data have been extracted with the purpose of studying probable changes in the social and psychopathologic conformation of the patients, in the last two decades.

Extra-embryonic function of Rb is essential for embryonic development and viability.

The retinoblastoma (Rb) gene was the first tumour suppressor identified. Inactivation of Rb in mice results in unscheduled cell proliferation, apoptosis and widespread developmental defects, leading to embryonic death by day 14.5 (refs 2-4).

Magnitude of peroxisome proliferator-activated receptor-gamma activation is associated with important and seemingly opposite biological responses in breast cancer cells.

Background: The nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARgamma) has become a potential target for the prevention and treatment of breast cancer. However, recent in vitro and in vivo studies have raised the question of whether activation of PPARgamma leads to the promotion or reduction of tumor formation. Studies using several cancer cell lines, animal models, and a variety of PPARgamma agonists have shown discordant results, including changes in cellular proliferation, differentiation, and apoptosis of cancer cells and tumors.

Influence of coenzyme A-independent transacylase and cyclooxygenase inhibitors on the proliferation of breast cancer cells.

Recent studies have demonstrated that arachidonic acid (AA) may serve as an important signal that blocks cell proliferation of certain neoplastic cells. The current study was conducted to determine whether disruption of AA homeostasis influences breast cancer cell proliferation and death. Initial experiments revealed that inhibition of AA remodeling through membrane phospholipids by inhibitors of the enzyme, coenzyme A-independent transacylase (CoA-IT), attenuates the proliferation of the estrogen receptor-negative, MDA-MB-231, and estrogen receptor-positive, MCF-7 breast cancer cell lines.