Specific Aptamer Functionalization of Dense Ceramic by Click Chemistry Towards Circulating Tumor Cells Apheresis.

Background/aim: Circulating tumor cells (CTC) are tumor cells which can be disseminated at distance of the primary tumor and form metastatic niche. Moreover, their quantity is an important parameter which can induce cluster metastasis. A solution, can be the creation of a system that allow the capture and elimination from the blood of patients by using the medical device developed which is an inert bioceramic functionalized by aptamer target to CTC.

Splicing factor ratio as an index of epithelial-mesenchymal transition and tumor aggressiveness in breast cancer.

Epithelial-to-mesenchymal transition (EMT) has been shown to be associated with tumor progression and metastasis. During this process in breast cancer, a crucial role is played by alternative splicing systems. To identify a new early prognostic marker of metastasis, we evaluated EMT-related gene expression in breast cell lines, and in primary tumor tissue from 31 patients with early breast cancer, focusing our attention on EMT-related splicing factors ESRP1, ESRP2 and RBFOX2.

Epithelial Mesenchymal Transition: a double-edged sword.

Epithelial mesenchymal transition (EMT) is a physiological process necessary to normal embryologic development. However in genesis of pathological situations, this transition can be perverted and signaling pathways have different regulations from those of normal physiology. In cancer invasion, such a mechanism leads to generation of circulating tumor cells.

Circulating tumor cells and epithelial, mesenchymal and stemness markers: characterization of cell subpopulations.

Until now detection and numeration of circulating tumor cells (CTCs) were essentially used as a prognostic factor in cancer progression. To extend the role of these kinds of analysis, it seems necessary to improve analytical methods related to isolation and characterization of CTCs. Discrepancies between published results corroborates this requirement.

After clouds sun again shines on circulating tumor cells research.

In the Science issue of first February 2013 Yu M et al. characterized epithelial and mesenchymal circulating tumor cells (CTC) by RNA-in situ hybridization. In this editorial we comment their results and emphasize the different CTC subpopulations arising from epithelial mesenchymal transition (EMT).

Mesenchymal characterization: alternative to simple CTC detection in two clinical trials.

Background: Breast cancer is one of the most common malignancies in women. Approximately 25% of patients with early-stage disease will develop metastatic recurrence. Two clinical trials were undertaken in order to detect circulating tumor cells (CTCs) in primary breast cancer.

Metformin: a rising star to fight the epithelial mesenchymal transition in oncology.

Metformin is a biguanide derivative which is widely prescribed as an oral drug for diabetes mellitus type 2. This old molecule has recently received a new attention because of its therapeutic properties in oncology, that seem to be independent of its action on glycemia homeostasis. The reappraisal of its pharmacological effects was supported by delineation of signaling pathways and more recently clinical trials.

Epithelial mesenchymal transition: a new insight into the detection of circulating tumor cells.

Many research groups reported on the relation between circulating tumor cells (CTCs) in peripheral blood and worse prognosis for metastatic cancer patients. These results are based on CTCs counting and did not take into account molecular characteristics of cells. To establish CTCs as a reliable and accurate biological marker, new technologies must be focused on CTC subpopulations: dedifferentiated circulating tumor cells (ddCTCs) arising from epithelial mesenchymal transition (EMT).

Mesenchymal and stemness circulating tumor cells in early breast cancer diagnosis.

Background: Epithelial mesenchymal transition (EMT) is a crucial event likely involved in dissemination of epithelial cancer cells. This process enables them to acquire migratory/invasive properties, contributing to tumor and metastatic spread. To know if this event is an early one in breast cancer, we developed a clinical trial.

FDG-PET/CT of head and neck squamous cell carcinoma in a rat model.

Purpose: The aim of this study was to demonstrate the ability to use human clinical positron emission tomography/computed tomography (PET/CT) to detect and investigate head and neck cancers chemically induced by 4-nitroquinoline-1-oxide (4-NQO) in a rat model.

Study Design: The study design was prospective animal research.

Procedures: A head and neck squamous cell carcinoma was established in 20 immunocompetent rats, who drank a 4-NQO solution during 16 weeks.

Improved agarose gel assay for quantification of growth factor-induced cell motility.

Cell chemotaxis is frequently required in normal or pathological situations such as invasion, metastasis, and tumor angiogenesis and may involve many different cell types. At present, no device can simultaneously (i) make morphological observations, (ii) quantify cell migration, (iii) test multiple chemoattracting gradients, and (iv) analyze cell-cell interactions. We developed an agarose-based assay to address these questions.

Molecular mechanisms regulating the angiogenic phenotype in tumors: clinical impact in the future.

Tumor progression depends on the angiogenic switch. In this review, we recapitulate the molecular mechanisms involved in this angiogenic switch. The rat osteosarcoma model employed would permit further studies in the sequential events leading to initial recruitment of blood vessels and could lead to development of an angiogenesis-based panel of circulating blood cells (endothelial cells, endothelial progenitor cells and accessory cells) that can be quantified and used to detect microscopic tumors or to follow the efficacy of antiangiogenic therapy.

Expression of 5-lipoxygenase (5-LOX) in T lymphocytes.

5-Lipoxygenase (5-LOX) is the key enzyme responsible for the synthesis of the biologically active leukotrienes. Its presence has been reported in cells of the myeloid lineage and B lymphocytes but has not been formally defined in T lymphocytes. In this study, we provide evidence for 5-LOX expression on both transcriptional and translational levels in highly purified peripheral blood T cells as well as in human T lymphoblastoid cell lines (MOLT4 and Jurkat).

Gene expression of HIF-1alpha and XRCC4 measured in human samples by real-time RT-PCR using the sigmoidal curve-fitting method.

Quantitative reverse transcription PCR (RT-PCR) has become an important tool for studying functional gene expression. However the most often used cycle threshold (CT)-based method, primarily related to the required amplification efficiency determination via serial dilution, can call into question the level of quantitative reliability and accuracy that can be achieved, in addition to the impracticalities inherent to CT-based methodologies. In this study, an alternative method, named the sigmoidal curve-fitting (SCF) method, was compared with the classic CT method for two target genes (XRCC4 and HIF-1alpha) and a reference gene (HPRT).

VEGFR-3, VEGF-C and VEGF-D mRNA quantification by RT-PCR in different human cell types.

The molecular events favoring lymphangiogenic pathways for tumor growth and dissemination are not perfectly understood, nor are the expression patterns of lymphangiogenic biomarkers such as the VEGFR-3 receptor and its ligands, VEGF-C and VEGF-D. In particular, VEGFR-3 expression is not restricted to the lymphatic endothelium, but is found on some cancer cells and other cell types. A quantitative RT-PCR method was set up to measure the mRNA levels of VEGFR-3, VEGF-C and VEGF-D.

A quantitative RT-PCR method to determine topoisomerase I mRNA levels in human tissue samples.

DNA topoisomerase I (Topo I) is involved in DNA replication, transcription, recombination and repair. Clinical interest has focused on Topo I as it is the molecular target of camptothecin (CPT), used in first and second lines of treatment for different cancer types. Furthermore, it is well demonstrated that the patients who best responded to CPT-based chemotherapy were generally those with the greatest tumoral Topo I expression and/or activity.

[Lymphatic vessels and cancer].

Survival and development of tumors depends on nutritional and respiratory biological events and exchanges ensured by blood and lymph. Tumor proliferation is associated with an increase in the vascular networks either near the tumor or intra-tumorally. Tumor tissues are able to increase their provisionment according to their needs while directing and optimizing the development of peri-tumoral vessels.

Overexpression of human GPX1 modifies Bax to Bcl-2 apoptotic ratio in human endothelial cells.

As they scavenge reactive oxygen species, antioxidants were studied for their ability to interfere with apoptotic processes. However, their mechanisms of action remain unclear. In this study, we measured the expression of two Bcl-2 family members, Bax and Bcl-2, in a human endothelial like cell-line overexpressing the organic hydroperoxide-scavenging enzyme glutathione peroxidase (GPX1), in the absence of any apoptotic/oxidant stimulus.

In vivo follow-up of rat tumor models with 2-deoxy-2-[F-18]fluoro-D-glucose/dual-head coincidence gamma camera imaging.

Unlabelled: Before studying the impact of 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) imaging with a dual-head coincidence gamma camera (DHC) for the follow-up of animal tumor models, we wanted to optimize this technique.

Methods: Three different animal tumor models (osteosarcoma, melanoma, and breast cancer) were studied after FDG injection. Dynamic and dual time point FDG/DHC imaging were studied from one hour to five hours postinjection.

Endostatin cDNA/cationic liposome complexes as a promising therapy to prevent lung metastases in osteosarcoma: study in a human-like rat orthotopic tumor.

Antiangiogenesis or destruction of tumor neovessels is an effective strategy to prevent tumor growth. Endostatin, one of the many inhibitors of angiogenesis that have been discovered, has shown conflicting results in preclinical assays. We studied the therapeutic potential of lipid/DNA complexes consisting of cationic liposomes and an endostatin-coding plasmid (Endo cDNA/CLP) in an orthotopic osteosarcoma model in rats.

PHGPx overexpression induces an increase in COX-2 activity in colon carcinoma cells.

Background: Lipid peroxidation is a constant problem that eukaryotic cells have to face. Glutathione peroxidases (GPx) are among the most effective systems that protect cells from hydroperoxide toxicity. The objective of this study was to evaluate the relationship between GPx and cyclooxygenase 2 (COX-2), implicated in cancer pathogenesis, particularly in colon cancer cells.

A new orthotopic model of human breast cancer in immunocompetent rats.

Background: Breast cancer is the first cause of mortality by cancer in women in North America and Western Europe. For non-estrogen-dependent tumors as well as for metastatic cancers, current therapies are of limited efficacy. Several animal models have been described but they are imperfect as they are poorly representative of what occurs in real tumors.