-
[show abstract]
[hide abstract]
ABSTRACT: Protein Z (PZ) is a vitamin K dependent protein acting as the cofactor of the protein Z dependent inhibitor (ZPI), in the inhibition of activated factor X bound on the phospholipids. Normal plasma protein Z concentrations have wide variations among individuals, partly explained by a genetic control. Several protein Z gene polymorphisms influence plasma concentration, separately and in combination. The role of PZ in blood coagulation regulation has been demonstrated in vitro. The responsibility of low PZ level in the occurrence of thrombosis has been questioned. However, the roles of PZ plasma level and PZ gene polymorphisms remain debated with conflicting results in arterial, venous, or placental thrombosis. These discrepancies can be explained by the heterogeneity of populations chosen as control, by the PZ interindividual variability, by the small size of the cohorts in mainly retrospective studies and perhaps by the lack of real important influence of this protein on coagulation. PZ measurement is not actually considered as a biological marker of thrombophilia. Large prospective studies remain to be done to investigate its possible role in thrombosis.
La Revue de Médecine Interne 04/2010; 31(8):551-7. · 0.61 Impact Factor
-
P Mirshahi,
A Rafii,
L Vincent,
A Berthaut,
R Varin,
G Kalantar,
C Marzac,
O A Calandini,
J-P Marie, C Soria,
J Soria,
M Mirshahi
[show abstract]
[hide abstract]
ABSTRACT: Angiogenesis is thought to be involved in the development of acute leukemia (AL). We investigated whether bone marrow stromal cells (BMSCs) derived from stem cells might be responsible for the increase in microvascular density (MVD), and compared 13 bone marrow samples from AL patients with 23 samples from patients in complete remission (controls). We demonstrated that AL-derived BMSC secreted more insulin growth factor-1 (IGF-1) and SDF-1alpha than controls. In addition, in contrast to normal adherent BMSCs, adherent BMSCs derived from CD133+/CD34+ stem cells from AL patients were able to form capillary-like structures ('vasculogenic mimicry') on Matrigel. The increase in vasculogenic mimicry occurred through PI3 kinase and rho GTPase pathway as inhibitors of these signaling pathways (wortmannin and GGTI-298, respectively) were able to reduce or prevent capillary tube formation. In normal BMSC, addition of exogenous IGF-1 generated capillary-like tubes through the same pathway as observed spontaneously in AL-derived BMSC. The involvement of IGF-1 in the mimicry process was confirmed by the addition of a neutralizing antibody against IGF-1R or a IGF-1R pathway inhibitor (picropodophyllin). In conclusion, AL-derived BMSC present functional abnormalities that may explain the increase in MVD in the bone marrow of AL patients.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 05/2009; 23(6):1039-48. · 8.30 Impact Factor
-
Annals of the New York Academy of Sciences 12/2006; 408(1):665 - 666. · 3.15 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Angiogenesis plays a significant role in a variety of malignant hematologic diseases, and it is recognized that it has prognostic value. However, the cellular mechanisms by which malignant hematologic cells induce angiogenesis are not well understood. In order to investigate the role of cells from B-cell chronic lymphocytic leukemia (B-CLL) and multiple myeloma (MM) in angiogenesis on human bone marrow endothelial cells (HBMEC), we analyzed the impact of factors secreted by B-CLL cells and by MM cells on HBMEC capillary tube formation on matrigel. It was found that, in addition to the secretion of angiogenic factors VEGF and b-FGF by B-CLL and MM cells, MM cells (but not B-CLL cells) induced a dramatic increase in expression of VEGFR-1 and VEGFR-3 on human bone marrow endothelial cells (HBMEC). It would seem that this increase in VEGFR-3 occurred via the ERK and mTOR pathways, since their respective inhibitors U0126, LY294002 or rapamycin were responsible for a decrease of VEGFR-3. In response to MM cells-increased VEGF receptors on HBMEC, endothelial cell migration was enhanced in a wound artificially produced in a semi-confluent HBMEC culture, a phenomenon which was also down-regulated by the same inhibitors that reversed the increase in VEGF receptors. The present study suggests that, in addition to the classic angiogenic pathway, another mechanism related to an increased expression of VEGFRs on HBMEC might exist in malignant hematopoietic angiogenesis.
Biochemical and Biophysical Research Communications 11/2006; 349(3):1003-10. · 2.48 Impact Factor
-
J-Y Pillé,
H Li,
E Blot,
J-R Bertrand,
L-L Pritchard,
P Opolon,
A Maksimenko,
H Lu,
J-P Vannier,
J Soria,
C Malvy, C Soria
[show abstract]
[hide abstract]
ABSTRACT: Overexpression of RhoA in cancer indicates a poor prognosis, because of increased tumor cell proliferation and invasion and tumor angiogenesis. We showed previously that anti-RhoA small interfering RNA (siRNA) inhibited aggressive breast cancer more effectively than conventional blockers of Rho-mediated signaling pathways. This study reports the efficacy and lack of toxicity of intravenously administered encapsulated anti-RhoA siRNA in chitosan-coated polyisohexylcyanoacrylate (PIHCA) nanoparticles in xenografted aggressive breast cancers (MDA-MB-231). The siRNA was administered every 3 days at a dose of 150 or 1500 microg/kg body weight in nude mice. This treatment inhibited the growth of tumors by 90% in the 150-microg group and by even more in the 1500-microg group. Necrotic areas were observed in tumors from animals treated with anti-RhoA siRNA at 1500 microg/kg, resulting from angiogenesis inhibition. In addition, this therapy was found to be devoid of toxic effects, as evidenced by similarities between control and treated animals for the following parameters: body weight gain; biochemical markers of hepatic, renal, and pancreatic function; and macroscopic appearance of organs after 30 days of treatment. Because of its efficacy and the absence of toxicity, it is suggested that this strategy of anti-RhoA siRNA holds significant promise for the treatment of aggressive cancers.
Human Gene Therapy 11/2006; 17(10):1019-26. · 4.22 Impact Factor
-
J-Y Pillé,
C Denoyelle,
J Varet,
J-R Bertrand,
J Soria,
P Opolon,
H Lu,
L-L Pritchard,
J-P Vannier,
C Malvy, C Soria,
H Li
[show abstract]
[hide abstract]
ABSTRACT: Overexpression of RhoA or RhoC in breast cancer indicates a poor prognosis, due to increased tumor cell proliferation and invasion and tumor-dependent angiogenesis. Until now, the strategy of blockage of the Rho-signaling pathway has used either GGTI or HMG-CoA reductase inhibitors, but they are not specific to RhoA or RhoC inhibition. In this study, a new approach with anti-RhoA and anti-RhoC siRNAs was used to inhibit specifically RhoA or RhoC synthesis. Two transfections of either RhoA or RhoC siRNA (8.5 nM) into MDA-MB-231 human breast cancer cells or HMEC-1 endothelial cells induced extensive degradation of the target mRNA and led to a dramatic decrease in synthesis of the corresponding protein. In vitro, these siRNAs inhibited cell proliferation and invasion more effectively than conventional blockers of Rho cell signaling. Finally, in a nude mouse model, intratumoral injections of anti-RhoA siRNA (100 microl at 85 nM) every 3 days for 20 days almost totally inhibited the growth and angiogenesis of xenografted MDA-MB-231 tumors. One may infer from these observations that specific inhibition of the Rho-signaling pathway with siRNAs represents a promising approach for the treatment of aggressive breast cancers.
Molecular Therapy 03/2005; 11(2):267-74. · 6.87 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Zoledronic acid (ZOL) is a nitrogen-containing bisphosphonate and its use in reducing osteoporosis and cancer-induced osteolysis is increasing. Recent findings indicated that ZOL has a direct effect on cancer cells. In this study, the effect of ZOL was examined on the aggressive MDA-MB-231 breast cancer cell line. ZOL induces an important inhibition of cell invasion at low concentrations (1 microM). This is not explained by modifications of proteases involved in cell invasiveness (matrix metalloproteinases and urokinase-type plasminogen activator), but by a disorganisation of actin cytoskeleton due to RhoA inhibition related to its defective prenylation as it was reversed by geranylgeraniol (GGOH) and mimicked by the Rho selective inhibitor C3 exoenzyme. In addition, ZOL inhibits the chemotactic effect induced by stromal cell-derived factor 1(SDF-1), a chemokine greatly involved in cancer metastasis to bone. This effect is related to both reduction of cell motility induced by RhoA inhibition and to a decreased expression of CXCR-4, the SDF-1 receptor. Finally, ZOL reduces Cox-2 expression and, consequently, the secretion of prostaglandins E2 (PGE2) in a RhoA-independent manner. This inhibition could contribute to bone protection in breast cancers because PGE2 stimulates osteoclast-mediated bone resorption. In summary, new insights in the mechanism of ZOL action on aggressive breast cancer cells are demonstrated and could explain its beneficial action in both the reduction of osteolysis and prevention of metastasis.
British Journal of Cancer 06/2003; 88(10):1631-40. · 5.04 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Fenofibrate, a peroxisome proliferator-activated receptor (PPAR)-alpha activator, used as a normolipidemic agent, is thought to offer additional beneficial effects in atherosclerosis. Since angiogenesis is involved in plaque progression, hemorrhage, and instability, the main causes of ischemic events, this study was designed to evaluate the action of fenofibrate on angiogenesis. Our results show that fenofibrate (i) inhibits endothelial cell proliferation induced by angiogenic factors, followed at high concentrations by an increase in apoptosis, (ii) inhibits endothelial cell migration in a healing wound model, (iii) inhibits capillary tube formation in vitro, and (iv) inhibits angiogenesis in vivo. Concerning the mechanism of action, the inhibition of endothelial cell migration by fenofibrate can be explained by a disorganization of the actin cytoskeleton. At the molecular level, fenofibrate markedly decreased basic fibroblast growth factor-induced Akt activation and cyclooxygenase 2 gene expression. This inhibition of angiogenesis could participate in the beneficial effect of fenofibrate in atherosclerosis.
Cellular and Molecular Life Sciences CMLS 05/2003; 60(4):810-9. · 6.57 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In breast cancers, clinical symptoms of inflammation localised around the tumour at the time of diagnosis have been considered to have poor prognosis significance. In this study, the biological mechanisms responsible for the deleterious action of monocytes in cancer were investigated. The incubation of the breast-cancer-derived MDA-MB231 cells with monocytes resulted in an increase in factors involved in cell invasion (i.e. both cancer cells and monocytes-associated urokinase and Tissue Factor, and PAI-1 and MMP-9 secretion). Moreover, the functions of monocytes were also modified. Incubation of monocytes with MDA-MB231 cancer cells resulted in a downregulation in the secretion of the antiproliferative cytokine Oncostatin M, while the apoptotic factor TNF alpha was dramatically increased. However, MDA-MB231 cancer cells have been shown to be resistant towards the apoptotic action of TNF alpha. These findings demonstrate that incubation of MDA-MB231 cancer cells with monocytes induced a crosstalk, which resulted in an increased expression of factors involved in cancer cell invasiveness and in a modification of monocytes function against cancer cells, while inflammatory effects were increased.
British Journal of Cancer 05/2003; 88(8):1207-12. · 5.04 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To investigate the pro-angiogenic effects of several multiple myeloma (MM) cell line culture supernatants on human bone marrow endothelial cell (HBMEC) proliferation, migration, and capillary formation, and the anti-angiogenic effects of thalidomide.
HBMEC was cultured in the presence of MM cell lines (IM9, XG1, U266 and MOLP-5) supernatants. Proliferation and migration of HBMEC were determined, capillary-like tubule formation of HBMEC was examined in fibrin and Matrigel. The inhibiting effect of thalidomide was investigated by adding it into myeloma cell line culture supernatants. Vascular endothelial growth factor (VEGF) was measured by ELISA.
(1) MM cell lines culture supernatants promoted HBMEC proliferation and migration. (2) In fibrin and Matrigel, capillary-like tubule network formation promoted by the supernatants. (3) All of these effects could be inhibited by thalidomide. (4) This effect was not related to VEGF in the supernatants.
MM cell line promote proliferation, migration and tubule formation by secreting VEGF or other several cytokines. Thalidomide can inhibit these effects.
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 11/2002; 23(10):520-3.
-
[show abstract]
[hide abstract]
ABSTRACT: The cancer chemopreventive agent apigenin also has strong cytostatic and anti-angiogenic effects in vitro. We now investigated its efficacy against experimental Lewis lung carcinomas (LLC), C-6 gliomas and DHDK 12 colonic cancers in vivo. Tumour bearing mice received 50 mg/kg/day apigenin in three different galenical formulations during 12 days in 8-hourly intervals. Only weak effects of apigenin on the size and the number of new tumour blood vessels of both established and newly transplanted tumours were recorded although the intratumoural necrosis was elevated (45 +/- 15% vs. 20 +/- 7% (control), p < 0.05%). These results contrast sharply with the high in vitro sensitivity of LLC, C-6, DHDK 12 and endothelial cells to apigenin where complete growth suppression occurs at concentrations beyond 30 g/ml. Possible causes are discussed.
Phytomedicine 09/2002; 9(6):489-95. · 3.27 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Oncostatin M (OSM) is a cytokine of the interleukin-6 (IL-6) family secreted by activated monocytes, and is expressed in atherosclerotic plaque. Smooth muscle cells (SMC), by expressing tissue factor (TF) and tissue factor pathway inhibitor (TFPI) can contribute to the thrombogenicity of atherosclerotic plaque. Consequently, the aim of this study was to evaluate the effects of OSM on the procoagulant activity of SMC. We observed that OSM induced in a concentration-dependent manner a potent procoagulant activity (PCA) that was related in part to an increased synthesis of TF, both at the cell membrane and in SMC lysates. The increased expression of TF on SMC membrane induced by OSM was sustained and was still observed 24 h after stimulation by OSM. IL-6 and leukaemia inhibitory factor (LIF), two OSM-related cytokines, did not significantly modify TF expression at the surface of SMC. In addition to its effects on TF, OSM decreased the secretion of TFPI in the supernatants of SMC, as well as in the lysates, but was devoid of effect on TFPI bound at the membrane of SMC. IL-6 and LIF reduced also TFPI secretion, which could explain why the PCA of SMC lysates treated by IL-6 or LIF was increased, despite an absence of effect on TF expression. In conclusion, these data support the hypothesis that by increasing the PCA of SMC, OSM might be involved in the thrombotic complications associated with plaque rupture.
Blood Coagulation and Fibrinolysis 08/2002; 13(5):449-55. · 1.24 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Cerivastatin is used in the treatment of hypercholesterolemia to inhibit 3-hydroxy 3-methylglutaryl coenzyme A reductase and thus prevent the synthesis of cholesterol precursors, such as farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP), responsible, respectively, for translocation of Ras and Rho to the cell membrane, a step required for their cell signaling, leading to cell proliferation and migration. Recently, it has been suggested that non lipid-related effects of statins could play a beneficial role in cancer therapy. In this study, we have investigated the mechanisms by which statins inhibit cancer and the types of cancers which could benefit from this therapy. In MDA-MB-231 cells, an aggressive breast cancer cell line with spontaneous activation of Ras and NFkappaB and overexpression of RhoA, cerivastatin induced inhibition of both cell proliferation and invasion through Matrigel. This anti-proliferative effect was related to G(1)/S arrest due to an increase in p21(Waf1/Cip1). The anti-invasive effect was observed from 18 h and could be explained by RhoA delocalization from the cell membrane, resulting in disorganization of the actin fibers and disappearance of focal adhesion sites. The importance of RhoA inactivation in both these inhibitory effects was proved by their reversion by GGPP but not by FPP. Moreover, cerivastatin was also shown to induce inactivation of NFkappaB, in a RhoA inhibition-dependent manner, resulting in a decrease in urokinase and metalloproteinase-9 expression, two proteases involved in cell migration. The participation of Ras inactivation is considered a subsidiary mechanism for the effects of cerivastatin, as they were not rescued by FPP. Prolonged treatment of MDA-MB-231 cells with high doses of cerivastatin induced a loss of cell attachment. Interestingly, the effect of cerivastatin was considerably lower on poorly invasive MCF-7 cells. In conclusion, our results suggest that cerivastatin inhibits cell signaling pathways involved in the invasiveness and metastatic properties of highly invasive cancers.
Carcinogenesis 09/2001; 22(8):1139-48. · 5.70 Impact Factor
-
Leukemia 08/2001; 15(7):1143-5. · 9.56 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Fibrinogen plays a complex role in hemostasis, thrombosis, and vascular disease. Hyperfibrinogenemia is an independent vascular risk factor and dysfibrinogenemia can provoke thrombosis. Afibrinogenemia is usually responsible for hemorrhagic diathesis, and unexpected ischemic lesions are intriguing. We report the case of an afibrinogenemic patient, who at the age of 30 developed ischemic lesions of the feet related to severe stenosis of the iliac and hypogastric arteries. The biopsy of the iliac artery lesion showed an intense myointimal hyperplasia. We performed standard hemostatic analysis and analyzed the activation markers of platelets and coagulation factors and the kinetics of thrombin generation in the patient and in normal control plasmas treated or not with reptilase. Occlusive arterial lesions were attributed to a disruptive hematoma penetrating the vascular lumen. Thrombin concentration after calcium addition increase markedly in the afibrinogenemic patient and in defibrinated normal plasma, as compared to untreated normal plasma. Thrombin-antithrombin complexes (T-AT) were markedly enhanced while F1+2 prothrombin fragments stayed in the normal range. These results suggested activation of coagulation and in vivo circulating thrombin. Thrombin activates the platelets that secrete growth factors for smooth muscle cells and generate the intimal hyperplasia. Recurrent hemorrhage within the vessel wall might induce injury and local thrombin generation. Thrombin not trapped by the clot is available for platelet activation and smooth muscle cell migration and proliferation. The absence of a protective fibrin cap on the intima might account for intima vulnerability and embolization. Afibrinogenemia appears in this paradoxical situation as a vascular risk factor.
Thrombosis Research 06/2001; 102(3):211-9. · 2.44 Impact Factor
-
J P Collet,
G Montalescot,
C Lesty,
Z Mishal,
J Soria,
R Choussat,
G Drobinski, C Soria,
P Pinton,
P Barragan,
D Thomas
[show abstract]
[hide abstract]
ABSTRACT: Abciximab plus aspirin improves the TIMI 3 flow rate of the infarct-related artery in patients treated with either percutaneous coronary intervention or thrombolysis. The present study investigated whether the reperfusion efficacy of abciximab relates to modifications of clot architecture in patients admitted for acute myocardial infarction (AMI). Methods and
A total of 23 AMI patients in the Abciximab before Direct angioplasty and stenting in Myocardial Infarction Regarding Acute and Long term follow-up (ADMIRAL) trial received, in a double-blind fashion, either abciximab (n=13) or placebo (n=10) before primary stenting. Viscoelastic (G' in dyne/cm(2)) and morphological (mean platelet aggregate surface area [SAG] in micrometer(2)) indexes of ex vivo platelet-rich clots (PRC) were assessed in a double-blind fashion before and after the bolus administration of abciximab or placebo. G' and SAG reflect the mechanical and morphological impact of activated platelets on the PRC fibrin network, respectively. Abciximab administration reduced G' by 63% (P=0.0001) and SAG by 65% (P=0.0007), and no effect was seen in the placebo group. These abciximab-related changes increased fibrin exposure as a consequence of the platelet-aggregate surface reduction and may have improved endogenous fibrinolysis. These effects were identified in all patients, independent of previous heparin administration.
Abciximab dramatically reduces platelet aggregate size and increases the fibrin accessibility of ex vivo PRC in AMI patients. These modifications could participate in the better coronary artery patency observed with abciximab.
Circulation 06/2001; 103(19):2328-31. · 14.74 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Recent studies have suggested that inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (statins) can play a role in protection against vascular risk, which is independent of cholesterol reduction. It could act by inhibiting the synthesis of isoprenoids (farnesylpyrophosphate (FPP) and geranylgeranylpyrophosphate (GGPP)), which are respectively essential for membrane attachment and biological activity of GTPases Ras and RhoA. This study demonstrates that a statin (cerivastatin) inhibits angiogenesis. This effect was due to a decrease in endothelial cell locomotion which was reversed by GGPP. It was mainly related to delocalization of RhoA from cell membrane to cytoplasm, responsible for the disorganization of actin stress fibers. Furthermore, a decrease in MMP-2 secretion, involved in cell invasion, was also observed. This effect is rather due to Ras inhibition as it was reversed by FPP. This anti-angiogenic activity could explain the beneficial effect of statins on atherosclerosis and on cancer prevention as shown by clinical studies.
FEBS Letters 05/2001; 495(3):159-66. · 3.54 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: TIMP-2 is a natural matrix metalloproteinase (MMP) inhibitor that prevents the degradation of extracellular matrix proteins. It abolishes the hydrolytic activity of all activated members of the metalloproteinase family and in particular that of MT1-MMP, MMP-2, and MMP-9, which are selective for type IV collagenolysis. Since MMPs have been implicated in both cancer progression and angiogenesis, we generated a recombinant adenovirus to deliver human TIMP-2 (AdTIMP-2) and evaluated its anticancer efficiency in three murine models. Our results demonstrated that overexpression in vitro of TIMP-2 inhibited the invasion of both tumor and endothelial cells without affecting cell proliferation. Its in vivo efficiency has been evaluated in murine lung cancer LLC, and colon cancer C51 in syngeneic mice as well as in human breast cancer MDA-MB231 in athymic mice. Preinfection of tumor cells by AdTIMP-2 resulted in an inhibition of tumor establishment in more than 50% of mice in LLC and C51 models and in 100% mice in the MDA-MB231 model. A single local injection of AdTIMP-2 into preestablished tumors of these three types significantly reduced tumor growth rates by 60--80% and tumor-associated angiogenesis index by 25--75%. Lung metastasis of LLC tumor was inhibited by >90%. In addition, AdTIMP-2-treated mice showed a significantly prolonged survival in all the cancer models tested. These data demonstrate the potential of adenovirus-mediated TIMP-2 therapy in cancer treatment.
Human Gene Therapy 04/2001; 12(5):515-26. · 4.22 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Sodium phenylacetate (NaPa), a non-toxic phenylalanine metabolite, has been shown to induce in vivo and in vitro cytostatic and antiproliferative effects on various cell types. In this work, we analysed the effect of NaPa on the invasiveness of breast cancer cell (MDA-MB-231, MCF-7 and MCF-7 ras). Using the highly invasive breast cancer cell line MDA-MB-231, we demonstrated that an 18-hour incubation with NaPa strongly inhibits the cell invasiveness through Matrigel (86% inhibition at 20 mM of NaPa). As cell invasiveness is greatly influenced by the expression of urokinase (u-PA) and its cell surface receptor (u-PAR) as well as the secretion of matrix metalloproteinases (MMP), we tested the effect of NaPa on these parameters. An 18-hour incubation with NaPa did not modify u-PA expression, either on MDA-MB-231 or on MCF-7 and MCF-7 ras cell lines, and induced a small u-PA decrease after 3 days of treatment of MDA-MB-321 with NaPa. In contrast, an 18 h incubation of MDA-MB-231 increased the expression of u-PAR and the secretion of MMP-9. As u-PAR is a ligand for vitronectin, a composant of the extracellular matrix, these data could explain the increased adhesion of MDA-MB-231 to vitronectin, while cell adhesivity of MCF-7 and MCF-7 ras was unmodified by NaPa treatment. NaPa induced also an increased expression of both Lymphocyte Function-Associated-1 (LFA-1) and Intercellular Adhesion Molecule-1 (ICAM-1), which was obvious from 18 hour incubation with NaPa for the MDA-MB-231 cells, but was delayed (3 days) for MCF-7 and MCF-7 ras. Only neutralizing antibodies against LFA-1 reversed the decreased invasiveness of NaPa-treated cells. Therefore we can conclude that the strong inhibition of MDA-MB-231 invasiveness is not due to a decrease in proteases involved in cell migration (u-PA and MMP) but could be related both to the modification of cell structure and an increased expression of adhesion molecules such as u-PAR and LFA-1.
British Journal of Cancer 04/2001; 84(6):802-7. · 5.04 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Prothrombotic phenotype has been described in protein-Z deficient mice, but the thrombotic risk associated with protein Z deficiency in human beings is unknown. We saw a protein Z plasma concentration deficiency of about 20% in 169 patients, from two hospitals, who had ischaemic stroke, whereas the frequency in 88 controls was about 5%. We saw no increase in the frequency of protein Z deficiency in 56 patients with venous thrombophilia. However, why protein Z deficiency was only observed in arterial thrombosis remains unknown.
The Lancet 04/2001; 357(9260):933-4. · 38.28 Impact Factor
