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Find video protocols related to scientific articles indexed in Pubmed.
A subset of bone marrow stromal cells regulate ATP-binding cassette gene expression via insulin-like growth factor-I in a leukemia cell line.
Int. J. Oncol.
PUBLISHED: 04-15-2014
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The importance of the insulin-like growth factor, IGF, as a signaling axis in cancer development, progression and metastasis is highlighted by its effects on cancer cells, notably proliferation and acquired resistance. The role of the microenvironment within which cancer cells evolve and which mediates this effect is far from clear. Here, the involvement of IGF-I in inducing multidrug resistance in a myeloid leukemia cell line, grown in the presence of bone marrow-derived stromal cells called 'Hospicells' (BMH), is demonstrated. We found that i) drug sensitive as well as resistant leukemia cells express IGF-I and its receptor IGF-IR. However, the resistant cells were found to secrete high levels of IGF-I. ii) Presence of exogenous IGF-I promoted cell proliferation, which decreased when an inhibitor of IGF-IR (picropodophyllin, PPP) was added. iii) BMH and IGF-I are both involved in the regulation of genes of the ATP binding cassette (ABC) related to resistance development (MDR1, MRP1, MRP2, MRP3 and BCRP). iv) The levels of ABC gene expression by leukemia cells were found to increase in the presence of increasing numbers of BMH. However, these levels decreased when IGF-IR was inhibited by addition of PPP. v) Co-culture of the drug-sensitive leukemia cells with BMH induced protection against the action of daunorubicin. This chemoresistance was amplified by the presence of IGF-I whereas it decreased when IGF-IR was inhibited. Our results underline the role of microenvironment in concert with the IGF-1 pathway in conferring drug resistance to leukemia cells.
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New combinational assay using soluble fibrin and d-dimer determinations: a promising strategy for identifying patients with suspected venous thromboembolism.
PLoS ONE
PUBLISHED: 01-01-2014
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To establish a new and reliable assay for quantification of the soluble fibrin (SF) in combination with that of D-dimer for early diagnosis of venous thromboembolism.
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Plasma endothelial protein C receptor influences innate immune response in ovarian cancer by decreasing the population of natural killer and TH17 helper cells.
Int. J. Oncol.
PUBLISHED: 03-07-2013
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In spite of the growing importance of endothelial protein C receptor/active protein C (EPCR/aPC) in tumor biology, their impact on immunological homeostasis remains largely unexplored. The objective of this study was to assess whether soluble plasma endothelial protein C receptor (sEPCR), which is a regulator of circulating aPC, is involved in innate immune response in cancer patients. In the Ovcar-3 ovarian cancer line, the role of aPC in secretion of cytokines was analyzed. In parallel, in 33 patients, with a diagnosis of ovarian epithelial cancer, sEPCR was quantified, blood immune cell phenotypes were determined by flow cytometry and plasma cytokines were evaluated using a protein array. Spearmans rank correlation coefficients (r) and coefficient significance was determined by a statistical hypothesis test (?=0.05). Our results show that i) aPC induced the secretion of several cytokines in Ovcar-3 cells; ii) 61% of patients exhibited a concentration of plasma sEPCR well above the baseline (normal plasma level, 100 ± 28 ng/ml); iii) comparing immune cell phenotypes in patients having a normal level of sEPCR with those having a high level of sEPCR, it was found that sEPCR levels were correlated with high intensity of cells expressing CD45ra, CD3, CD8, CD25 and low intensity of cells expressing CD56 (NK cells), CD294 (TH2 cells), IL-2, IL-10, IL-17a (TH17 cells), IL-21 (TH21 cells) and CD29 markers (r ? 0.60); and iv) high levels of sEPCR correlate with high levels of plasma bioactive proteins such as insulin-like growth factor-2 (IGFII), IL-13r?, macrophage inflammatory protein (MIP1?) and matrix metalloproteinase-7 (MMP-7) that have already been proposed as biomarkers for ovarian cancer and particularly those with poor prognosis. In conclusion, sEPCR produced by ovarian cancer cells, by modulating circulating aPC, influences the secretory behavior of tumor cells (cytokines and interleukins). Consequently, sEPCR in turn acts on the innate immune response by decreasing effector cells such as natural killer and T helper cells (TH2, TH17 and TH21).
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Hospicells promote upregulation of the ATP-binding cassette genes by insulin-like growth factor-I via the JAK2/STAT3 signaling pathway in an ovarian cancer cell line.
Int. J. Oncol.
PUBLISHED: 02-19-2013
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Interaction between tumor cells and their micro-environment has a crucial role in the development, progression and drug resistance of cancer. Our objective was to confirm the role of Hospicells, which are stromal cells from the cancer microenvironment, in drug resistance and tumor cell growth. We demonstrated that soluble factors secreted by Hospicells activate several genes and upregulate the JAK/STAT signaling pathway in ovarian cancer cell lines. Hospicells express all insulin-like growth factor (IGF) family as detected by gene array, RT-PCR, protein array and immunocytochemistry. While focusing attention on the microenvironment, we considered the role of IGF-I in proliferation and survival of ovarian cancer cells. Indeed, IGF-I is a major regulator of different stages of cancer development. We studied the effect of exogenously added IGF-I on the regulation of ATP-binding cassette (ABC) genes (MDR1, MRP1, MRP2, MRP3, MRP5 and BCRP) in the ovarian cancer cell line OVCAR3 and validated the results obtained using the IGF-IR antagonist picropodophyllin. IGF-I regulates the expression of ABC genes in OVCAR3 cells via the PI3-kinase, MEK and JAK2/STAT3 signaling pathways. The OVCAR3 cell line when co-cultured with Hospicells showed a marked degree of drug resistance. The drug resistance observed could be amplified with exogenous IGF-I. Addition of IGF-IR inhibitor, however, reduced the degree of resistance in these exposed cells. Cells that were treated with anticancer drugs and then exposed to IGF-I showed an increase in drug resistance and, thereby, an increase in cell survival. This observation indicates that drug resistance of OVCAR3 cells increases when there is synergy between OVCAR3 cells and Hospicells and it is amplified when IGF-I was exogenously added. In conclusion, inhibition of IGF-IR and targeting of the JAK2/STAT3 signaling pathway can be a target for ovarian cancer therapy.
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Rac3 induces a molecular pathway triggering breast cancer cell aggressiveness: differences in MDA-MB-231 and MCF-7 breast cancer cell lines.
BMC Cancer
PUBLISHED: 01-30-2013
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Rho GTPases are involved in cellular functions relevant to cancer. The roles of RhoA and Rac1 have already been established. However, the role of Rac3 in cancer aggressiveness is less well understood.
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Whole blood clots are more resistant to lysis than plasma clots--greater efficacy of rivaroxaban.
Thromb. Res.
PUBLISHED: 01-11-2013
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Defective thrombolysis, a thrombotic risk factor, can be attributed to the formation of a compact clot poorly accessible to fibrinolytic enzymes. Venous thrombi, rich in red blood cells (RBCs), and arterial thrombi containing various amounts of RBCS, plasma and whole blood (WB) clot permeability and degradability were compared. The effect of rivaroxaban, a potent direct factor Xa inhibitor, was also evaluated.
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Ovarian cancer: Stat3, RhoA and IGF-IR as therapeutic targets.
Cancer Lett.
PUBLISHED: 04-12-2011
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Seeking to improve ovarian cancer therapy, we compared biological characteristics of the moderately-aggressive OVCAR-3 cell line with two highly aggressive ovarian cancer cell populations: the SK-OV-3 cell line, and HASCJ primary cells isolated from the ascitic fluid of a patient with FIGO stage IV ovarian cancer. Secretion of angiogenic factors was not discriminative, whereas cell invasion through Matrigel and vasculogenic mimicry were much greater in the more aggressive cells. Among 10 agents tested for their ability to decrease cancer cell aggressivity using these two models, inhibitors of Stat3, IGF-IR and Rho GTPase were found to be the most promising.
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Stimulation of angiogenesis resulting from cooperation between macrophages and MDA-MB-231 breast cancer cells: proposed molecular mechanism and effect of tetrathiomolybdate.
BMC Cancer
PUBLISHED: 07-17-2010
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Infiltration by macrophages (Mphi) indicates a poor prognosis in breast cancers, in particular by inducing angiogenesis. Our study aimed 1) to investigate the mechanism by which cooperation between Mphi and aggressive breast cancer cells (MDA-MB-231) induces angiogenesis; 2) to examine the effect of tetrathiomolybdate (TM) on this angiogenic activity.
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Matrix metalloproteinase-9 is required for tubular network formation and migration of resistant breast cancer cells MCF-7 through PKC and ERK1/2 signalling pathways.
Cancer Lett.
PUBLISHED: 03-04-2010
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Matrix metalloproteinase-9 (MMP-9) strongly influences tumor development and metastasis. Using resistant (rMCF-7) and sensitive (sMCF-7) breast cancer lines we investigated the role of MMP-9 in cell migration (CM) and tubular network (TN) formation, two processes implied in tumor growth and metastasis. Our data demonstrate that MMP-9 which is critical for CM is necessary but not sufficient for TN formation and suggest a link between MDR1/P-gp and constitutive MMP-9. Both TN formation and CM are dependent on PKC and ERK1/2 pathways. This study reinforces the logic of combining therefore MMP inhibitors in cancer therapy, especially in patients with chemoresistance and invasion/metastasis.
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Soluble endothelial protein C receptor (sEPCR) is likely a biomarker of cancer-associated hypercoagulability in human hematologic malignancies.
Cancer Med
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Elevated plasma level of soluble endothelial protein C receptor (sEPCR) may be an indicator of thrombotic risk. The present study aims to correlate leukemia-associated hypercoagulability to high level plasma sEPCR and proposes its measurement in routine clinical practice. EPCR expressions in leukemic cell lines were determined by flow cytometry, immunocytochemistry, and reverse transcription polymerase chain reaction (RT-PCR). EPCR gene sequence of a candidate cell line HL-60 was also determined. Plasma samples (n = 76) and bone marrow aspirates (n = 72) from 148 patients with hematologic malignancies and 101 healthy volunteers were analyzed by enzyme-linked immunosorbent assay (ELISA) via a retrospective study for sEPCR and D-dimer. All leukemic cell lines were found to express EPCR. Also, HL-60 EPCR gene sequence showed extensive similarities with the endothelial reference gene. All single nucleotide polymorphisms (SNPs) originally described and some new SNPs were revealed in the promoter and intronic regions. Among these patients 67% had plasma sEPCR level higher than the controls (100 ± 28 ng/mL), wherein 16.3% patients had experienced a previous thrombotic event. These patients were divided into: group-1 (n = 45) with amount of plasmatic sEPCR below 100 ng/mL, group-2 (n = 45) where the concentration of sEPCR was between 100 and 200, and group-3 (n = 20) higher than 200 ng/mL. The numbers of thrombotic incidence recorded in each group were four, six, and eight, respectively. These results reveal that EPCR is expressed not only by a wide range of human malignant hematological cells but also the detection of plasma sEPCR levels provides a powerful insight into thrombotic risk assessment in cancer patients, especially when it surpasses 200 ng/mL.
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Endothelial protein C receptor expressed by ovarian cancer cells as a possible biomarker of cancer onset.
Int. J. Oncol.
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Coagulation disorders often accompany cancer onset and evolution, which, if not properly managed, could have grave consequences. Endothelial protein C is an important regulator of homeostasis and acts through its high affinity binding to its transmembrane receptor (EPCR). Soluble (sEPCR) which results from the proteolytic cleavage of the membrane bound form can trap activated endothelial protein C and deprive it of its anti-coagulant function. In this study, the expression of EPCR and its soluble form (sEPCR) released into plasma as a result of proteolytic cleavage were investigated in ovarian, breast, lung and colorectal cancer biopsies, as well as in ascitic cell clusters and peritoneal fluid from ovarian cancer samples. In parallel, breast, ovarian, lung and colorectal cancer cell lines were investigated for the expression of EPCR. The integrity of the EPCR gene sequence as well gene haplotypes were ascertained in the established cancer cell lines in order to understand their eventual regulatory functions. The results from the present study indicate that in cancer patients, the levels of sEPCR are significantly higher than the normal range compared to healthy volunteers. The increase in the levels of sEPCR parallels the increase in CA125, showing a close correlation. Therefore, the detection of sEPCR in cancer and during the post-treatment period could be taken into account as an additional marker that could re-inforce the one obtained using CA125 alone as a marker of cancer cell mass.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.