Omental Preadipocytes Stimulate Matrix Remodeling and IGF Signaling to Support Ovarian Cancer Metastasis.

Ovarian cancer can metastasize to the omentum, which is associated with a complex tumor microenvironment. Omental stromal cells facilitate ovarian cancer colonization by secreting cytokines and growth factors. An improved understanding of the tumor-supportive functions of specific cell populations in the omentum could identify strategies to prevent and treat ovarian cancer metastasis.

Flotillin-2 regulates epidermal growth factor receptor activation, degradation by Cbl-mediated ubiquitination, and cancer growth.

Epidermal growth factor receptor (EGFR) signaling is frequently dysregulated in various cancers. The ubiquitin ligase Casitas B-lineage lymphoma proto-oncogene (Cbl) regulates degradation of activated EGFR through ubiquitination and acts as an adaptor to recruit proteins required for trafficking. Here, we used stable isotope labeling with amino acids in cell culture mass spectrometry to compare Cbl complexes with or without epidermal growth factor (EGF) stimulation.

TWEAK-Fn14-RelB Signaling Cascade Promotes Stem Cell-like Features that Contribute to Post-Chemotherapy Ovarian Cancer Relapse.

Unlabelled: Disease recurrence in high-grade serous ovarian cancer may be due to cancer stem-like cells (CSC) that are resistant to chemotherapy and capable of reestablishing heterogeneous tumors. The alternative NF-κB signaling pathway is implicated in this process; however, the mechanism is unknown. Here we show that TNF-like weak inducer of apoptosis (TWEAK) and its receptor, Fn14, are strong inducers of alternative NF-κB signaling and are enriched in ovarian tumors following chemotherapy treatment.

Characterization of SOX2, OCT4 and NANOG in Ovarian Cancer Tumor-Initiating Cells.

The identification of tumor-initiating cells (TICs) has traditionally relied on surface markers including CD133, CD44, CD117, and the aldehyde dehydrogenase (ALDH) enzyme, which have diverse expression across samples. A more reliable indication of TICs may include the expression of embryonic transcription factors that support long-term self-renewal, multipotency, and quiescence. We hypothesize that SOX2, OCT4, and NANOG will be enriched in ovarian TICs and may indicate TICs with high relapse potential.

MEDI3039, a novel highly potent tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) receptor 2 agonist, causes regression of orthotopic tumors and inhibits outgrowth of metastatic triple-negative breast cancer.

Background: TNF-related apoptosis-inducing ligand (TRAIL) receptor agonists are attractive anti-tumor agents because of their capability to induce apoptosis in cancer cells by activating death receptors (DR) 4 and 5 with little toxicity against normal cells. Despite an attractive mechanism of action, previous clinical efforts to use TRAIL receptor agonists have been unsuccessful. In this study, we examined MEDI3039, a highly potent multivalent DR5 agonist, in breast cancer cell lines and in vivo models.

ONC201 kills breast cancer cells by targeting mitochondria.

We report a novel mechanism of action of ONC201 as a mitochondria-targeting drug in cancer cells. ONC201 was originally identified as a small molecule that induces transcription of TNF-related apoptosis-inducing ligand (TRAIL) and subsequently kills cancer cells by activating TRAIL death receptors. In this study, we examined ONC201 toxicity on multiple human breast and endometrial cancer cell lines.

From caveman companion to medical innovator: genomic insights into the origin and evolution of domestic dogs.

The phenotypic and behavioral diversity of the domestic dog has yet to be matched by any other mammalian species. In their current form, which comprises more than 350 populations known as breeds, there is a size range of two orders of magnitude and morphological features reminiscent of not only different species but also different phylogenetic families. The range of both appearance and behavior found in the dog is the product of millennia of human interference, and though humans created the diversity it remains a point of fascination to both lay and scientific communities.

Genome annotation by shotgun inactivation of a native gene in hemizygous cells: application to BRCA2 with implication of hypomorphic variants.

The greatest interpretive challenge of modern medicine may be to functionally annotate the vast variation of human genomes. Demonstrating a proposed approach, we created a library of BRCA2 exon 27 shotgun-mutant plasmids including solitary and multiplex mutations to generate human knockin clones using homologous recombination. This 55-mutation, 13-clone syngeneic variance library (SyVaL) comprised severely affected clones having early-stop nonsense mutations, functionally hypomorphic clones having multiple missense mutations emphasizing the potential to identify and assess hypomorphic mutations in novel proteomic and epidemiologic studies, and neutral clones having multiple missense mutations.

PIK3CA and AKT1 mutations have distinct effects on sensitivity to targeted pathway inhibitors in an isogenic luminal breast cancer model system.

Purpose: Activating mutations in the phosphoinositide-3-kinase (PI3K)/AKT/mTOR pathway are present in the majority of breast cancers and therefore are a major focus of drug development and clinical trials. Pathway mutations have been proposed as predictive biomarkers for efficacy of PI3K-targeted therapies. However, the precise contribution of distinct PI3K pathway mutations to drug sensitivity is unknown.

Biological clues to potent DNA-damaging activities in food and flavoring.

Population differences in age-related diseases and cancer could stem from differences in diet. To characterize DNA strand-breaking activities in selected foods/beverages, flavorings, and some of their constituent chemicals, we used p53R cells, a cellular assay sensitive to such breaks. Substances testing positive included reference chemicals: quinacrine (peak response, 51×) and etoposide (33×); flavonoids: EGCG (19×), curcumin (12×), apigenin (9×), and quercetin (7×); beverages: chamomile (11×), green (21×), and black tea (26×) and coffee (3-29×); and liquid smoke (4-28×).

Age distribution, polyps and rectal cancer in the Egyptian population-based cancer registry.

Aim: To describe the clinical and epidemiologic profiles of the disease and to compare the findings with those generated from the previous hospital-based studies.

Methods: The Gharbiah cancer registry is the only population-based cancer registry in Egypt since 1998. We analyzed the data of all colorectal cancer patients included in the registry for the period of 1999-2007.

Clinical profile, BRCA2 expression, and the androgen receptor CAG repeat region in Egyptian and Moroccan male breast cancer patients.

Introduction: Male breast cancer (MBC) is a rare disease. Rates of MBC in Northern Africa vary by region. The age-standardized incidence for MBC is higher in Morocco than in Egypt, and the Egyptian rate is similar to the U.

Androgen receptor polyglutamine tract length in Egyptian male breast cancer patients.

Male breast cancer (MBC) is a rare disease in the U.S., accounting for less than 1% of all breast cancers.