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81.
Agns C. Noël Myriam Polette Jean-Marc Lewalle Carine Munaut Herv P. Emonard Philippe Birembaut Jean-Michel Foidart 《International journal of cancer. Journal international du cancer》1994,56(3):331-336
Gelatinases/type-IV collagenases are metalloproteinases involved in some carcinoma invasion and metastatic processes. The exact cellular source of the 72-kDa gelatinase A is controversial. We have analyzed the expression of mRNA coding for gelatinase A in vivo by in situ hybridization on breast-cancer tissues. The mRNA for gelatinase A was present in fibroblasts. We have therefore evaluated the gelatinase-A activity in vitro, in co-cultures of different breast adenocarcinoma cell lines and human fibroblasts. In monoculture, none of the tumor cells tested produced detectable amounts of gelatinase A. The gelatinase-A activity was enhanced in cultures of fibroblasts maintained in the presence of MDA-MB 231 or SKBR3 cells, or their conditioned medium. This increased enzymatic activity was evidenced both in the culture medium and in the membrane fraction and was paralleled by enhancement of the steady-state levels of mRNA. These results are an in vitro demonstration of a regulation of fibroblasts gelatinase-A production by soluble factors secreted by breast-tumor cells. 相似文献
82.
Matrix and serine protease expression during leukemic cell differentiation induced by aclacinomycin and all-trans-retinoic acid 总被引:3,自引:0,他引:3
Devy L Hollender P Munaut C Colige A Garnotel R Foidart JM Noël A Jeannesson P 《Biochemical pharmacology》2002,63(2):179-189
In myeloid leukemia, immature leukemic cells are able to egress into peripheral blood to infiltrate extra-medullary organs. We therefore analyzed the migrating and invasive potential of human HL-60 and NB4 cell lines, representative of acute myelogenous leukemia, their ability to express matrix metalloproteases (MMPs), tissue inhibitors of metalloproteases (TIMPs) and urokinase plasminogen activator (uPA) in response to differentiating agents. Granulocytic differentiation by all-trans-retinoic acid (ATRA) and aclacinomycin (ACLA) strongly increased HL-60 and NB4 cell migration and invasion. At mRNA and protein levels, these cell lines produced significant amounts of MMP-9 (HL-60相似文献
83.
It is well documented that VMAT2 protects nigrostriatal DA neurons against MPP(+) by sequestering it inside vesicles away from its mitochondrial site of neurotoxic action. However, the implication of the VMAT2 in the mechanism of action exerted by 6-OHDA has received little attention. Therefore, the aim of the present study was to determine whether the vesicular sequestration of 6-OHDA would protect dopaminergic neurons from its toxicity similarly to what is observed with MPP(+). We injected mice with 6-OHDA 90 min after TBZ treatment. Since, unexpectedly, TBZ pretreatment prevented 6-OHDA neurotoxicity, we performed a similar experience replacing 6-OHDA with MPP(+) in order to check our experimental protocol. TBZ pretreatment similarly prevented MPP(+) neurotoxicity. This discrepancy with what is commonly describe in the literature, led us to use reserpine. Indeed, the long lasting VMAT2 inhibition induced by reserpine allowed us to inject neurotoxins while mice no longer presented hypothermia. Contrary to TBZ pretreatment, reserpine pretreatment potentiated both 6-OHDA and MPP(+) toxicity on dopaminergic neurons. Hypothermia elicited by TBZ appeared to be responsible, at least in part, for the neuroprotective effect observed. To verify this hypothesis, we investigated the influence of hypothermia on the toxic activity of both neurotoxins. A hypothermia similar to that induced by TBZ was obtained by a forced swimming test of putting mice into cool water (23 degrees C). The hypothermia prevented both 6-OHDA and MPP(+)-induced neurotoxicity. We finally reported that VMAT2 inhibition potentiates both MPP(+) and 6-OHDA neurotoxicity. 相似文献
84.
Supratikto G Wirth ME Achadi E Cohen S Ronsmans C 《Bulletin of the World Health Organization》2002,80(3):228-234
A district-based audit of maternal and perinatal mortality began during 1994 in three provinces of South Kalimantan, Indonesia. Both medical and non-medical factors were documented and an effort was made to progress from merely assessing substandard care to recommending improvements in access to care and the quality of care. Extensive discussions of cases of maternal death were held during regular meetings with providers, policy-makers and community members. The sources of information included verbal autopsies with family members and medical records. Between 1995 and 1999 the audit reviewed 130 maternal deaths. The leading causes of death were haemorrhage (41%) and hypertensive diseases (32%). Delays in decision-making and poor quality of care in health facilities were seen as contributory factors in 77% and 60% of the deaths, respectively. Economic constraints were believed to have contributed to 37% of the deaths. The distance between a patient's home and a health provider or facility did not appear to have a significant influence, nor did transport problems. The audit led to changes in the quality of obstetric care in the district. Its success was particularly attributable to the process of accountability of both health providers and policy-makers and to improved working relationships between health providers at different levels and between providers and the community. With a view to the continuation and further expansion of the audit it may be necessary to reconsider the role of the provincial team, the need of health providers for confidentiality, the added benefit of facility-based audits, the need to incorporate scientific evidence into the review process, and the possible consideration of severe complications as well as deaths. It may also be necessary to recognize that village midwives are not solely responsible for maternal deaths. 相似文献
85.
Docagne F Nicole O Gabriel C Fernández-Monreal M Lesné S Ali C Plawinski L Carmeliet P MacKenzie ET Buisson A Vivien D 《Molecular and cellular neurosciences》2002,21(4):634-644
The intravenous injection of the serine protease, tissue-type plasminogen activator (t-PA), has shown to benefit stroke patients by promoting early reperfusion. However, it has recently been suggested that t-PA activity, in the cerebral parenchyma, may also potentiate excitotoxic neuronal death. The present study has dealt with the role of the t-PA inhibitor, PAI-1, in the neuroprotective activity of the cytokine TGF-beta1 and focused on the transduction pathway involved in this effect. We demonstrated that PAI-1, produced by astrocytes, mediates the neuroprotective activity of TGF-beta 1 against N-methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity. This t-PA inhibitor, PAI-1, protected neurons against NMDA-induced neuronal death by modulating the NMDA-evoked calcium influx. Finally, we showed that the activation of the Smad3-dependent transduction pathway mediates the TGF-beta-induced up-regulation of PAI-1 and subsequent neuroprotection. Overall, this study underlines the critical role of the t-PA/PAI-1 axis in the regulation of glutamatergic neurotransmission. 相似文献
86.
Sounni NE Baramova EN Munaut C Maquoi E Frankenne F Foidart JM Noël A 《International journal of cancer. Journal international du cancer》2002,98(1):23-28
Membrane-type metalloproteinase-1 (MT1-MMP) is a transmembrane metalloproteinase overexpressed in tumors, which plays a major role in the first step of pro-MMP-2 activation, leading to the generation of an intermediate 62 kDa species. The second step of MMP-2 activation that yields to the mature form is less understood and could involve an autocatalytic process and/or the activity of the plasminogen/plasmin system. Human melanoma A2058 cells, which express MMP-2 only in its pro-form, were used to determine the role of MT1-MMP during pericellular proteolysis and tumor progression. The induction of MT1-MMP overexpression by MT1-MMP cDNA transfection initiated the first step of MMP-2 activation. We provide evidence that a cooperation between the plasminogen/plasmin system and MT1-MMP endowed the cells with the ability to fully activate MMP-2 and with enhanced invasive properties in vitro. When injected subcutaneously in nude mice, MT1-MMP expressing clones induced rapid tumor growth and high tumor vascularization, while the control clones were poorly or not tumorigenic. Our data provide the first demonstration, in an experimental model, that MT1-MMP expression by tumor cells promotes tumor vascularization. 相似文献
87.
Body mass index in relation to ovarian cancer: a multi-centre nested case-control study 总被引:2,自引:0,他引:2
Lukanova A Toniolo P Lundin E Micheli A Akhmedkhanov A Muti P Zeleniuch-Jacquotte A Biessy C Lenner P Krogh V Berrino F Hallmans G Riboli E Kaaks R 《International journal of cancer. Journal international du cancer》2002,99(4):603-608
The incidence of ovarian cancer is up to 10 times higher in Western countries than in rural Asia and Africa. One common consequence of a Western lifestyle is the development of excessive body weight and obesity. A multi‐centre prospective study was conducted to investigate the association between body mass index (BMI) and ovarian cancer risk. A case‐control study was nested within 3 prospective cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). Information on anthropometry, demographic characteristics, medical history and lifestyle was obtained at the time of subjects' recruitment in each cohort. Women diagnosed with primary, invasive epithelial ovarian cancer from the 3 cohorts (n = 122) diagnosed 12 months or later after recruitment into the respective cohort served as case subjects. For each case subject, 2 control subjects that matched the case subject on cohort, menopausal status, age and date of recruitment were randomly identified. Data were analyzed by conditional logistic regression. There was an inverse association between BMI and ovarian cancer risk. For increasing quartiles of BMI above the lowest, the ORs were 0.62 (0.32–1.21), 0.59 (0.30–1.17) and 0.46 (0.23–0.92), p = 0.03. Analyses limited to women diagnosed 3 or more years after recruitment into the cohorts did not alter these findings. When obese women (BMI > 30) were compared to lean women (BMI ≤ 23), the inverse association became stronger, with an OR of 0.38 (0.17–0.85), p < 0.02. There was some evidence of direct association of ovarian cancer with height, which was limited to cancers diagnosed before age 55. Our data suggest that increasing body weight may confer a protection against ovarian cancer. © 2002 Wiley‐Liss, Inc. 相似文献
88.
The effects of neurotrophic factors on necrotic neuronal death are controversial. In this study we found that both neurotrophin-4 (NT-4) and basic fibroblast growth factor (bFGF) potentiated necrotic neuronal death caused by exposure to oxygen-glucose deprivation or iron-citrate (Fe) in cortical cultures. However, there were significant differences in the actions of the two neurotrophic factors. Neurotrophin-4 protected against apoptotic neuronal death, while bFGF had no effect on apoptotic death in these cultures. Furthermore, potentiation of oxygen-glucose deprivation induced necrotic death by NT-4 required pretreatment (24 h), while pretreatment with bFGF had no effect. However, acute treatment with bFGF during oxygen-glucose deprivation did potentiate neuronal death. Both neurotrophic factors potentiated free radical mediated necrotic neuronal death induced by exposure to Fe. However, the RNA synthesis inhibitor, actinomycin-D, blocked the injury potentiation by NT-4, but not that caused by bFGF. Also, NT-4, but not bFGF, potentiated Fe induced necrotic death in pure neuronal cultures. Expression of mRNA for FGF receptors FGFR1 and FGFR2 was observed at high levels in astrocytes. The results indicate that the injury enhancing effects of bFGF are acute, while those of NT-4 require prolonged exposure and new protein synthesis. Furthermore, the effects of bFGF appear to be mediated through actions on astrocytes, while NT-4 appears to act directly on neurons. The fact that neurotrophic factors from two distinct families can potentiate neuronal death by two different mechanisms suggests that such injury potentiation may be a common concern regarding the use of neurotrophic factors. 相似文献
89.
Karachi C François C Parain K Bardinet E Tandé D Hirsch E Yelnik J 《The Journal of comparative neurology》2002,450(2):122-134
This anatomic study presents an analysis of the distribution of calbindin immunohistochemistry in the human striatopallidal complex. Entire brains were sectioned perpendicularly to the mid-commissural line into 70-microm-thick sections. Every tenth section was immunostained for calbindin. Calbindin labeling exhibited a gradient on the basis of which three different regions were defined: poorly labeled, strongly labeled, and intermediate. Corresponding contours were traced in individual sections and reformatted as three-dimensional structures. The poorly labeled region corresponded to the dorsal part of the striatum and to the central part of the pallidum. The strongly labeled region included the ventral part of the striatum, the subcommissural part of the external pallidum but also the adjacent portion of its suscommissural part, and the anterior pole of the internal pallidum. The intermediate region was located between the poorly and strongly labeled regions. As axonal tracing and immunohistochemical studies in monkeys show a similar pattern, poorly, intermediate, and strongly labeled regions were considered as the sensorimotor, associative, and limbic territories of the human striatopallidal complex, respectively. However, the boundaries between these territories were not sharp but formed gradients of labeling, which suggests overlapping between adjacent territories. Similarly, the ventral boundary of the striatopallidal complex was blurred, suggesting a structural intermingling with the substantia innominata. This three-dimensional partitioning of the human striatopallidal complex could help to define functional targets for high-frequency stimulation with greater accuracy and help to identify new stimulation sites. 相似文献
90.
Hyperhomocysteinemia and venous thromboembolism: a risk factor more prevalent in the elderly and in idiopathic cases 总被引:2,自引:0,他引:2
Hainaut P Jaumotte C Verhelst D Wallemacq P Gala JL Lavenne E Heusterspreute M Zech F Moriau M 《Thrombosis research》2002,106(2):121-125
Fasting plasma homocysteine level and the related clinical findings were analysed in 240 consecutive patients with venous thromboembolism. Hyperhomocysteinemia, defined as a plasma level above 20 micromol/l (corresponding to the percentile 95th in the controls), was present in 11.2% of the patients. Plasma homocysteine level was similar in patients presenting with either deep venous thrombosis, pulmonary embolism or both conditions. It was significantly higher in patients with primary (unprovoked) VTE than in patients with secondary disease (associated with at least one risk factor): 12.3 vs. 9.55 micromol/l (p < 0.005). Mean homocysteine was higher in male than in female patients (14.51 vs. 12.9 micromol/l, p < 0.05) and increased significantly with age. Hyperhomocysteinemia was more frequent in patients with relapsing disease (14 of 76, 18.4%) than in those presenting with a single episode (13 of 164, 7.9%) (p = 0.034). Furthermore, hyperhomocysteinemia was correlated with reduced protein C level (p = 0.013). In a multivariate analysis, two factors were significantly associated with hyperhomocysteinemia: older age (p < 0.0001) and idiopathic occurrence (p < 0.02). Since the frequency of homozygous MTHFR thermolabile variant was rather similar in patients and controls, testing for C677T mutation was not helpful in screening VTE patients. However, the homozygous mutation was significantly more prevalent among hyperhomocysteinemia patients, confirming its role in the genesis of hyperhomocysteinemia. According to its prevalence, to the putative role in venous and arterial disease and the availability of an effective and low-cost corrective therapy, hyperhomocysteinemia deserves interest, especially in the elderly and in the patients with idiopathic VTE disease. 相似文献