Plasma hPG (Circulating Progastrin) as a Novel Prognostic Biomarker for early-stage breast cancer in a breast cancer cohort.

Background: Recurrence and metastases are still frequent outcomes after initial tumour control in women diagnosed with breast cancer. Although therapies are selected based on tumour characteristics measured at baseline, prognostic biomarkers can identify those at risk of poor outcomes. Circulating progastrin or hPG was found to be associated with survival outcomes in renal and hepatocellular carcinomas and was a plausible prognostic biomarker for breast cancer.

hPG (Circulating Progastrin), a Novel Blood-Based Biomarker for Detection of Poorly Differentiated Neuroendocrine Carcinoma and Well Differentiated Neuroendocrine Tumors.

Current blood-based biomarkers for neuroendocrine neoplasms (NENs) lack both sensitivity and specificity. Human circulating progastrin (hPG) is a novel biomarker that can be easily measured in plasma by ELISA. This study is the first to examine hPG in NENs.

Plasma hPG (Circulating Progastrin) as a Novel Prognostic Biomarker for Hepatocellular Carcinoma.

Alpha-fetoprotein (AFP) is the most widely used biomarker for hepatocellular carcinoma (HCC) prognosis. However, AFP is not useful in establishing a prognosis for patients with a tumor in the early stages. hPG (circulating progastrin) is a tumor promoting peptide present in the blood of patients with various cancers, including HCC.

A novel method to detect hPG (human circulating progastrin) in the blood.

hPG (human circulating progastrin) is produced and released by cancer cells. We recently reported that hPG is detected in the blood of patients with cancers from different origins, suggesting its potential utility for cancer detection. To accurately measure hPG in the blood of patients, we developed the DxPG test, a sandwich Enzyme-Linked Immunosorbent Assay (ELISA).

Prognostic Value of Plasma hPG (Circulating Progastrin) in Metastatic Renal Cell Carcinoma.

Precise management of kidney cancer requires the identification of prognostic factors. hPG (circulating progastrin) is a tumor promoting peptide present in the blood of patients with various cancers, including renal cell carcinoma (RCC). In this study, we evaluated the prognostic value of plasma hPG in 143 prospectively collected patients with metastatic RCC (mRCC).

The oncogenic and druggable hPG80 (Progastrin) is overexpressed in multiple cancers and detected in the blood of patients.

Background: In colorectal cancer, hPG80 (progastrin) is released from tumor cells, promotes cancer stem cells (CSC) self-renewal and is detected in the blood of patients. Because the gene GAST that encodes hPG80 is a target gene of oncogenic pathways that are activated in many tumor types, we hypothesized that hPG80 could be expressed by tumors from various origins other than colorectal cancers, be a drug target and be detectable in the blood of these patients.

Methods: hPG80 expression was monitored by fluorescent immunohistochemistry and mRNA expression in tumors from various origins.

Targeting the Wnt Pathway and Cancer Stem Cells with Anti-progastrin Humanized Antibodies as a Potential Treatment for K-RAS-Mutated Colorectal Cancer.

Patients with metastatic colorectal cancer suffer from disease relapse mainly due to cancer stem cells (CSC). Interestingly, they have an increased level of blood progastrin, a tumor-promoting peptide essential for the self-renewal of colon CSCs, which is also a direct β-catenin/TCF4 target gene. In this study, we aimed to develop a novel targeted therapy to neutralize secreted progastrin to inhibit Wnt signaling, CSCs, and reduce relapses.

Identification of a pharmacologically tractable Fra-1/ADORA2B axis promoting breast cancer metastasis.

Metastasis confronts clinicians with two major challenges: estimating the patient's risk of metastasis and identifying therapeutic targets. Because they are key signal integrators connecting cellular processes to clinical outcome, we aimed to identify transcriptional nodes regulating cancer cell metastasis. Using rodent xenograft models that we previously developed, we identified the transcription factor Fos-related antigen-1 (Fra-1) as a key coordinator of metastasis.

[Cellular senescence and the myth of Janus].

Cellular senescence is, essentially, a permanent proliferation arrest induced by various cellular stresses or inappropriate stimuli. This arrest, which is associated with dramatic changes in cell morphology, metabolism and gene expression, involves a complex signalling network aiming at stable inactivation of CDKs, major cell cycle regulators. Notably, several tumour suppressors, such as p53, pRb or p16(Ink4a), play key roles both in the initiation of the senescence program and in its maintenance, which often involves epigenetic changes.

Rejuvenating senescent and centenarian human cells by reprogramming through the pluripotent state.

Direct reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) provides a unique opportunity to derive patient-specific stem cells with potential applications in tissue replacement therapies and without the ethical concerns of human embryonic stem cells (hESCs). However, cellular senescence, which contributes to aging and restricted longevity, has been described as a barrier to the derivation of iPSCs. Here we demonstrate, using an optimized protocol, that cellular senescence is not a limit to reprogramming and that age-related cellular physiology is reversible.

p53 and p16(INK4A) independent induction of senescence by chromatin-dependent alteration of S-phase progression.

Senescence is triggered by various cellular stresses that result in genomic lesions and DNA damage response activation. However, the role of chromatin and DNA replication in senescence induction remains elusive. Here we show that downregulation of p300 histone acetyltransferase activity induces senescence by a mechanism that is independent of the activation of p53, p21(CIP1) and p16(INK4A).

SUMOylation of DRIL1 directs its transcriptional activity towards leukocyte lineage-specific genes.

DRIL1 is an ARID family transcription factor that can immortalize primary mouse fibroblasts, bypass RAS(V12)-induced cellular senescence and collaborate with RAS(V12) or MYC in mediating oncogenic transformation. It also activates immunoglobulin heavy chain transcription and engages in heterodimer formation with E2F to stimulate E2F-dependent transcription. Little, however, is known about the regulation of DRIL1 activity.

Cellular senescence in vivo: a barrier to tumorigenesis.

Cellular senescence is characterized by a largely irreversible cell cycle arrest that can be triggered by many types of intrinsic and extrinsic stress. These include telomere malfunction, oncogene activation and tumor suppressor gene inactivation. Ultimately, such events culminate in the activation of a tumor suppressor gene network.

Mesenchymal stem cell features of Ewing tumors.

The cellular origin of Ewing tumor (ET), a tumor of bone or soft tissues characterized by specific fusions between EWS and ETS genes, is highly debated. Through gene expression analysis comparing ETs with a variety of normal tissues, we show that the profiles of different EWS-FLI1-silenced Ewing cell lines converge toward that of mesenchymal stem cells (MSC). Moreover, upon EWS-FLI1 silencing, two different Ewing cell lines can differentiate along the adipogenic lineage when incubated in appropriate differentiation cocktails.

EWS/FLI-1 silencing and gene profiling of Ewing cells reveal downstream oncogenic pathways and a crucial role for repression of insulin-like growth factor binding protein 3.

Ewing tumors are characterized by abnormal transcription factors resulting from the oncogenic fusion of EWS with members of the ETS family, most commonly FLI-1. RNA interference targeted to the junction between EWS and FLI-1 sequences was used to inactivate the EWS/FLI-1 fusion gene in Ewing cells and to explore the resulting phenotype and alteration of the gene expression profile. Loss of expression of EWS/FLI-1 resulted in the complete arrest of growth and was associated with a dramatic increase in the number of apoptotic cells.

Absence of major defects in non-homologous DNA end joining in human breast cancer cell lines.

Structural abnormalities of chromosomes, including translocations and deletions, are extremely frequent in human cancer cells and particularly in breast cancer cells. One hypothesis to account for these alterations is a deficiency in the repair of DNA double-strand breaks (DSB). This repair process relies on two distinct pathways, homologous recombination (HR) and non-homologous DNA end joining (NHEJ).