RATIONALE: AE-941 may help to slow the growth of multiple myeloma.
PURPOSE: Phase II trial to study the effectiveness of neovastat in treating patients who have relapsed or refractory multiple myeloma.

Start Date01 Apr 2001

Sponsor / Collaborator

Æterna Zentaris, Inc.

NCT00005995 / CompletedPhase 3

AE-941 (NEOVASTAT) Versus Placebo in Metastatic Renal Cell Carcinoma Patients Who Are Refractory to Immunotherapy

RATIONALE: AE-941 may stop the growth of kidney cancer by stopping blood flow to the tumor.
PURPOSE: Randomized phase III trial to determine the effectiveness of AE-941 in treating patients who have metastatic kidney cancer that has not responded to biological therapy.

Start Date01 Oct 2000

Sponsor / Collaborator

Æterna Zentaris, Inc.

100 Clinical Results associated with MMPs x VEGFR

100 Translational Medicine associated with MMPs x VEGFR

0 Patents (Medical) associated with MMPs x VEGFR

835

Literatures (Medical) associated with MMPs x VEGFR

01 Dec 2024·Placenta

Placenta may exert fetal protection against maternal high salt diet intake via renin-angiotensin-aldosterone system

Article

Author: Stupin, Ana ; Kolobarić, Nikolina ; Vulin, Martina ; Rolić, Tara ; Magušić, Lucija ; Mihaljević, Zrinka ; Mandić, Sanja ; Šušnjara, Petar ; Šerić, Vatroslav ; Muller, Andrijana ; Drenjančević, Ines

OBJECTIVEThis study investigated the effects of high compared to normal dietary salt intake on fetoplacental vascular function, activity of renin-angiotensin-aldosterone system (RAAS), placental pro- and anti-angiogenic factors and biomarkers of placental remodeling and oxidative stress during healthy uncomplicated pregnancy.MATERIALS AND METHODSBased on their 24-h sodium excretion pregnant women (37-40 weeks' gestation) were categorized into three groups: normal salt (NS, <5.75 g/day, N = 12), high salt (HS, 5.75-10.25 g/day, N = 36), and very high salt (VHS, >10.25 g/day, N = 17). Pulsatility (PI) and resistive index of middle cerebral artery (MCA) and umbilical artery, plasma renin activity (PRA), serum aldosterone, soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) concentrations, as well as placental vascular endothelial growth factor C (VEGF-C), oxidative/antioxidative stress markers (TBARS/FRAP) and matrix metalloproteinase 9 (MMP-9) concentration were measured.RESULTSPI MCA was significantly decreased in HS/VHS groups compared to NS group. HS/VHS intake did not suppress PRA and aldosterone concentration. Serum PlGF concentration was significantly increased while sFlt-1 concentration and sFlt-1/PlGF ratio were significantly decreased in VHS group compared to NS group. MMP-9, VEGF-C concentration, TBARS and FRAP in placental tissue were similar between study groups.CONCLUSIONSHS/VHS diet does not suppress RAAS during pregnancy; however, it is associated with decreased PI MCA, a significantly decreased sFlt-1/PlGF ratio and unchanged biomarkers of placental remodeling or oxidative stress in healthy pregnant women, suggesting the presence of a possible protective or compensatory mechanism aimed at preserving placental function and pregnancy outcome itself in terms of maternal HS intake.

01 Nov 2024·Biomedicine & Pharmacotherapy

Microglia-mediated endothelial protection: the role of SHPL-49 in ischemic stroke

Article

Author: Zhang, Pei ; Zhao, Yu ; Zhang, Jiange

It was previously shown that SHPL-49, a glycoside derivative of salidroside formed through structural modification, exhibited neuroprotective effects in a rat cerebral ischemia model of permanent middle cerebral artery occlusion (pMCAO). Additionally, SHPL-49 enhanced the mRNA expression of vascular endothelial growth factor-a (Vegf-a) in macrophages. Microglia, functioning as resident macrophages within the brain, promptly respond to cerebral ischemia and engage in interactions with the cells of the Glial-Vascular Unit to orchestrate nerve injury responses. We postulated that the neuroprotective effects of SHPL-49 were mediated through microglia-dependent amelioration of endothelial dysfunction following cerebral ischemia. The present study demonstrates that SHPL-49 effectively mitigated microglia-dependent endothelial dysfunction in the pMCAO model by upregulating the expression of VEGF and suppressing the release of MMP-9 from microglia. Further MRI analyses confirmed that SHPL-49 significantly reduced nerve and endothelial function when microglia were depleted in the brains of pMCAO rats. The above phenomenon was also confirmed in the in vitro experiment investigating microglia-mediated brain endothelial cell function. Furthermore, we discovered that SHPL-49 activates the VEGFR2/Akt/eNOS pathways in endothelial cells and suppresses the p38 MAPK/MMP-9 pathways in microglia cells, thereby facilitating brain endothelial cell protection. Altogether, we have demonstrated that SHPL-49 effectively ameliorates endothelial dysfunction induced by cerebral ischemia through a microglia-dependent mechanism, thereby providing more valuable insights and references for the clinical evaluation of SHPL-49 injection for ischemic stroke.

01 Nov 2024·Anti-Cancer Agents in Medicinal Chemistry

Pseudolaric Acid B Inhibits FLT4-induced Proliferation and Migration in Non-small Cell Lung Cancer

Article

Author: Gao, Jiapan ; Ma, Weina ; Ren, Bingxi ; Ma, Xiaoyu ; Lei, Panpan ; Zhang, Yuxiu ; Liang, Jinna ; Su, Xinyue

Objectives:Non-Small Cell Lung Cancer (NSCLC) has attracted much attention on account of the high incidence and mortality of cancers. Vascular Endothelial Growth Factor Receptor 3 (VEGFR3/FLT4), which is a highly expressed receptor in NSCLC, greatly regulates cancer proliferation and migration. Pseudolaric Acid B (PAB) is a diterpenoid acid with antitumor activity isolated from Pseudolarix kaempferi. This study aimed to explore the inhibitory effect of PAB targeting FLT4 in NSCLC.Methods:Cell membrane chromatography was used to evaluate the affinity of PAB binding on FLT4. NCIH1299 cells were used in this study, and an MTT assay was performed to determine the anti-proliferation effect of PAB. Cell cycle analysis was conducted to study the cycle arrest of PAB. Wound healing and Transwell assays assessed the rate of cell migration. Western blot analysis evaluated the expression of related proteins.Results:PAB showed strong affinity to FLT4 with a KD value of 3.01 × 10- 6 M. Targeting FLT4 by PAB inactivated downstream P38MAPK and PI3K/AKT pathways, which inhibited the proliferation of NCI-H1299 cells. Meanwhile, PAB promoted G2/M phase arrest by influencing CyclinB1 and CDK1 complex formation to inhibit NCI-H1299 cell growth, but the effect was attenuated by knocking down the FLT4. Besides, PAB regulated MMP9 secretion through the Wnt/β-catenin signaling pathway to inhibit NCI-H1299 cell migration. However, the ability of PAB to inhibit migration was significantly weakened by FLT4 knockdown in NCI-H1299 cells.Conclusion:PAB can inhibit the proliferation and migration of NSCLC cells through targeting FLT4 and is expected to be a promising FLT4 inhibitor for NSCLC treatment.

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