Endothelial Cells Promote Colorectal Cancer Cell Survival by Activating the HER3-AKT Pathway in a Paracrine Fashion.

The regulation of colorectal cancer cell survival pathways remains to be elucidated. Previously, it was demonstrated that endothelial cells (EC) from the liver (liver parenchymal ECs or LPEC), the most common site of colorectal cancer metastases, secrete soluble factors in the conditioned medium (CM) that, in turn, increase the cancer stem cell phenotype in colorectal cancer cells. However, the paracrine effects of LPECs on other colorectal cancer cellular functions have not been investigated.

A Survey on Data Reproducibility and the Effect of Publication Process on the Ethical Reporting of Laboratory Research.

The successful translation of laboratory research into effective therapies is dependent upon the validity of peer-reviewed publications. However, several publications in recent years suggested that published scientific findings could be reproduced only 11% to 45% of the time. Multiple surveys attempted to elucidate the fundamental causes of data irreproducibility and underscored potential solutions, more robust experimental designs, better statistics, and better mentorship.

Macrophage conditioned medium promotes colorectal cancer stem cell phenotype via the hedgehog signaling pathway.

Background: There is conflicting data on the role of macrophages in colorectal cancer (CRC); some studies have shown that macrophages can exert an anti-tumor effect whereas others show that macrophages are tumor promoting. We sought to determine the role of conditioned medium (CM) from macrophages, in particular classically activated macrophages, on the development of the CSC phenotype in CRC cells, which is believed to mediate tumor growth and chemoresistance.

Methods: Murine (CT26) and human (HCP-1) CRC cell lines were treated with CM from lipopolysaccharide (LPS)-activated murine macrophages.

Intracrine VEGF signalling mediates colorectal cancer cell migration and invasion.

Background: Vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) are key regulators of angiogenesis, affecting endothelial cell survival and function. However, the effect of VEGF-VEGFR signalling on tumour cell function is not well understood. Our previous studies in colorectal cancer (CRC) cells have demonstrated an intracrine VEGF/VEGFR1 signalling mechanism that mediates CRC cell survival and chemo-sensitivity.

Subspecies Influences Proinflammatory Cytokine Expression and Monocyte Activation in Human Colorectal Tumors.

Chronic infection and associated inflammation have long been suspected to promote human carcinogenesis. Recently, certain gut bacteria, including some in the genus, have been implicated in playing a role in human colorectal cancer development. However, the species and subspecies involved and their oncogenic mechanisms remain to be determined.

Endothelial cells activate the cancer stem cell-associated NANOGP8 pathway in colorectal cancer cells in a paracrine fashion.

In colorectal cancer (CRC), cancer stem cells (CSCs) have been hypothesized to mediate cell survival and chemoresistance. Previous studies from our laboratory described a role for liver parenchymal endothelial cells (LPECs) in mediating the CSC phenotype in CRC cells in a paracrine/angiocrine fashion. The objectives of this study were to determine whether endothelial cells (ECs) from different organs can induce the CSC phenotype in CRC cells and to elucidate the signaling pathways involved.

Intracrine VEGF Signaling Mediates the Activity of Prosurvival Pathways in Human Colorectal Cancer Cells.

The effects of vascular endothelial growth factor-A (VEGF-A/VEGF) and its receptors on endothelial cells function have been studied extensively, but their effects on tumor cells are less well defined. Studies of human colorectal cancer cells where the VEGF gene has been deleted suggest an intracellular role of VEGF as a cell survival factor. In this study, we investigated the role of intracrine VEGF signaling in colorectal cancer cell survival.

A Disintegrin and Metalloproteinase Domain 17 Regulates Colorectal Cancer Stem Cells and Chemosensitivity Via Notch1 Signaling.

Evidence is accumulating for the role of cancer stem cells (CSCs) in mediating chemoresistance in patients with metastatic colorectal cancer (mCRC). A disintegrin and metalloproteinase domain 17 (ADAM17; also known as tumor necrosis factor-α-converting enzyme [TACE]) was shown to be overexpressed and to mediate cell proliferation and chemoresistance in CRC cells. However, its role in mediating the CSC phenotype in CRC has not been well-characterized.

VEGFR-1 Pseudogene Expression and Regulatory Function in Human Colorectal Cancer Cells.

Unlabelled: A large number of pseudogenes have been found to be transcribed in human cancers. However, only a few pseudogenes are functionally characterized. Here, we identified a transcribed pseudogene of VEGFR1, or fms-related tyrosine kinase 1 (FLT1), in human colorectal cancer cells.

CD44 expression contributes to trastuzumab resistance in HER2-positive breast cancer cells.

Resistance to HER2-targeted therapies remains a major obstacle in the treatment of HER2-overexpressing breast cancer. CD44, a putative breast cancer stem cell (CSC) marker, is overexpressed in trastuzumab-resistant breast cancer cells. While CSC-related genes may play a role in the development of trastuzumab resistance, conflicting results have been published about CSC response to trastuzumab.

HER family kinase domain mutations promote tumor progression and can predict response to treatment in human breast cancer.

Resistance to HER2-targeted therapies remains a major obstacle in the treatment of HER2-overexpressing breast cancer. Understanding the molecular pathways that contribute to the development of drug resistance is needed to improve the clinical utility of novel agents, and to predict the success of targeted personalized therapy based on tumor-specific mutations. Little is known about the clinical significance of HER family mutations in breast cancer.

Biological effect of human serum collected before and after oral intake of Pygeum africanum on various benign prostate cell cultures.

Pygeum africanum (Tadenan) is a popular phytotherapeutic agent used in the treatment of symptomatic benign prostatic hyperplasia. The active compounds of the drug have not been identified, and determining the plasma concentration of the drug is, therefore, not possible. Because there are conflicting results on the efficacy of this drug, we aimed to investigate its effect on prostate cell growth in vitro using human serum collected before and after Pygeum africanum intake.

Endoplasmic reticulum is a main localization site of mTORC2.

The Akt kinase is a critical effector in growth factor signaling. Activation of Akt driven by the growth factor dependent PI3K (phosphatidylinositol-3-OH kinase) is coupled to the plasma membrane translocation and phosphorylation of Akt on two sites by PDK1 (phosphoinositide-dependent protein kinase-1) on Thr-308 and by mTORC2 (mammalian Target of Rapamycin Complex 2) on Ser-473. In our study we examined the sub-cellular localization of mTORC2 and identified that this kinase complex predominantly resides on endoplasmic reticulum (ER).

Serum CD44 levels and overall survival in patients with HER2-positive breast cancer.

CD44 is an adhesion molecule involved in tumor cell invasion and metastasis. The function of CD44 in breast cancer is not understood completely, or is its role as a predictive or prognostic factor. In this study, we tested for the hypothesis that the concentration of soluble CD44 (sCD44) in serum is correlated with clinicopathological factors, especially HER2, and survival in patients with breast cancer.

Fatty acid synthase phosphorylation: a novel therapeutic target in HER2-overexpressing breast cancer cells.

Introduction: The human epidermal growth factor receptor 2 (HER2) is a validated therapeutic target in breast cancer. Heterodimerization of HER2 with other HER family members results in enhanced tyrosine phosphorylation and activation of signal transduction pathways. HER2 overexpression increases the translation of fatty acid synthase (FASN), and FASN overexpression markedly increases HER2 signaling, which results in enhanced cell growth.

Rictor phosphorylation on the Thr-1135 site does not require mammalian target of rapamycin complex 2.

In animal cells, growth factors coordinate cell proliferation and survival by regulating the phosphoinositide 3-kinase/Akt signaling pathway. Deregulation of this signaling pathway is common in a variety of human cancers. The PI3K-dependent signaling kinase complex defined as mammalian target of rapamycin complex 2 (mTORC2) functions as a regulatory Ser-473 kinase of Akt.

Pygeum africanum extract inhibits proliferation of human cultured prostatic fibroblasts and myofibroblasts.

Objective: To investigate the effect of Pygeum africanum (PA) extract on the proliferation of cultured human prostatic myofibroblasts and fibroblasts; this extract is used for treating urinary disorders associated with benign prostatic hyperplasia (BPH).

Materials And Methods: Primary cultures of prostatic stromal cells were obtained from histologically confirmed human BPH by enzymatic digestion. Cell proliferation was measured by 5-bromo2'-deoxy-uridine (BrdU) incorporation assays, and cytotoxicity by luminescent quantification of adenylate kinase activity.

Differentiated rabbit prostatic stromal cells in primary culture display functional alpha1A-adrenoceptors.

Aims: BPH is characterized by uncontrolled proliferation and increased contractility of prostatic smooth muscle cells. The activation of alpha1-adrenoceptors (alpha1-AR) seems involved in the latter event, but the lack of in vitro models expressing these receptors has hampered a more specific characterization of their role. In order to do so, we attempted to develop a new model of rabbit cultured prostatic stromal cells (PSC) in a non-proliferative and differentiated state.