VEGFC acts as a double-edged sword in renal cell carcinoma aggressiveness.


:Hypoxic zones are common features of metastatic tumors. Due to inactivation of the von Hippel-Lindau gene (VHL), renal cell carcinomas (RCC) show constitutive stabilization of the alpha subunit of the hypoxia-inducible factor (HIF). Thus, RCC represents a model of chronic hypoxia. Development of the lymphatic network is dependent on vascular endothelial growth factor C (VEGFC) and lies at the front line of metastatic spreading. Here, we addressed the role of VEGFC in RCC aggressiveness and the regulation of its expression in hypoxia. Methods: Transcriptional and post transcriptional regulation of VEGFC expression was evaluated by qPCR and with reporter genes. The involvement of HIF was evaluated using a siRNA approach. Experimental RCC were performed with immuno-competent/deficient mice using human and mouse cells knocked-out for the VEGFC gene by a CRISPR/Cas9 method. The VEGFC axis was analyzed with an online available data base (TCGA) and using an independent cohort of patients. Results: Hypoxia induced VEGFC protein expression but down-regulated VEGFC gene transcription and mRNA stability. Increased proliferation, migration, over-activation of the AKT signaling pathway and enhanced expression of mesenchymal markers characterized VEGFC-/- cells. VEGFC-/- cells did not form tumors in immuno-deficient mice but developed aggressive tumors in immuno-competent mice. These tumors showed down-regulation of markers of activated lymphocytes and M1 macrophages, and up-regulation of M2 macrophages markers and programmed death ligand 1 (PDL1). Over-expression of lymphangiogenic genes including VEGFC was linked to increased disease-free and overall survival in patients with non-metastatic tumors, whereas its over-expression correlated with decreased progression-free and overall survival of metastatic patients. Conclusion: Our study revisited the admitted dogma linking VEGFC to tumor aggressiveness. We conclude that targeting VEGFC for therapy must be considered with caution.






Ndiaye PD,Dufies M,Giuliano S,Douguet L,Grépin R,Durivault J,Lenormand P,Glisse N,Mintcheva J,Vouret-Craviari V,Mograbi B,Wurmser M,Ambrosetti D,Rioux-Leclercq N,Maire P,Pagès G




Has Abstract


2019-01-21 00:00:00












  • Polysaccharide nanosystems for future progress in cardiovascular pathologies.

    abstract::Natural polysaccharides have received a lot of attention in the biomedical field. Indeed, sources of polysaccharides, extracted or produced from plants, bacteria, fungi or algae, are diverse and renewable. Moreover, recent progresses in polysaccharide chemistry and nanotechnologies allow elaborating new dedicated nano...


    pub_type: 杂志文章,评审


    authors: Silva AK,Letourneur D,Chauvierre C

    更新日期:2014-03-11 00:00:00

  • Drug Repurposing Screening Identifies Tioconazole as an ATG4 Inhibitor that Suppresses Autophagy and Sensitizes Cancer Cells to Chemotherapy.

    abstract::Background: Tumor cells require proficient autophagy to meet high metabolic demands and resist chemotherapy, which suggests that reducing autophagic flux might be an attractive route for cancer therapy. However, this theory in clinical cancer research remains controversial due to the limited number of drugs that speci...


    pub_type: 杂志文章


    authors: Liu PF,Tsai KL,Hsu CJ,Tsai WL,Cheng JS,Chang HW,Shiau CW,Goan YG,Tseng HH,Wu CH,Reed JC,Yang LW,Shu CW

    更新日期:2018-01-01 00:00:00

  • Multiplexed non-invasive tumor imaging of glucose metabolism and receptor-ligand engagement using dark quencher FRET acceptor.

    abstract::Rationale: Following an ever-increased focus on personalized medicine, there is a continuing need to develop preclinical molecular imaging modalities to guide the development and optimization of targeted therapies. Near-Infrared (NIR) Macroscopic Fluorescence Lifetime Förster Resonance Energy Transfer (MFLI-FRET) imag...


    pub_type: 杂志文章


    authors: Rudkouskaya A,Sinsuebphon N,Ochoa M,Chen SJ,Mazurkiewicz JE,Intes X,Barroso M

    更新日期:2020-08-15 00:00:00

  • Stimuli-Responsive Nanotheranostics for Real-Time Monitoring Drug Release by Photoacoustic Imaging.

    abstract::Molecular photoacoustic imaging (PA) is a promising technology to understand tumor pathology and guide precision therapeutics. Despite the capability of activatable PA probes to image tumor-specific biomarkers, limitations in their molecular structure hamper them from effective drug delivery and the drug release monit...


    pub_type: 杂志文章


    authors: Yang Z,Song J,Tang W,Fan W,Dai Y,Shen Z,Lin L,Cheng S,Liu Y,Niu G,Rong P,Wang W,Chen X

    更新日期:2019-01-01 00:00:00

  • Salvia miltiorrhiza-derived miRNAs suppress vascular remodeling through regulating OTUD7B/KLF4/NMHC IIA axis.

    abstract::Objective: Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are essential for vascular remodeling. Natural compounds with diterpene chinone or phenolic acid structure from Salvia miltiorrhiza, an eminent medicinal herb widely used to treat cardiovascular diseases in China, can effectively a...


    pub_type: 杂志文章


    authors: Yang GS,Zheng B,Qin Y,Zhou J,Yang Z,Zhang XH,Zhao HY,Yang HJ,Wen JK

    更新日期:2020-06-19 00:00:00

  • Exome Sequencing of Oral Squamous Cell Carcinoma Reveals Molecular Subgroups and Novel Therapeutic Opportunities.

    abstract::Oral squamous cell carcinoma (OSCC), an epithelial malignancy affecting a variety of subsites in the oral cavity, is prevalent in Asia. The survival rate of OSCC patients has not improved over the past decades due to its heterogeneous etiology, genetic aberrations, and treatment outcomes. Improvement in therapeutic st...


    pub_type: 杂志文章


    authors: Su SC,Lin CW,Liu YF,Fan WL,Chen MK,Yu CP,Yang WE,Su CW,Chuang CY,Li WH,Chung WH,Yang SF

    更新日期:2017-02-26 00:00:00

  • Nanotopography-based lymphatic delivery for improved anti-tumor responses to checkpoint blockade immunotherapy.

    abstract::Rationale: Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is a co-inhibitory checkpoint receptor that is expressed by naïve T-cells in lymph nodes (LNs) to inhibit activation against "self" antigens (Ags). In cancer, anti-CTLA-4 blocks inhibitory action, enabling robust activation of T-cells against tumor Ags pr...


    pub_type: 杂志文章


    authors: Kwon S,Velasquez FC,Rasmussen JC,Greives MR,Turner KD,Morrow JR,Hwu WJ,Ross RF,Zhang S,Sevick-Muraca EM

    更新日期:2019-10-22 00:00:00

  • IL20RA signaling enhances stemness and promotes the formation of an immunosuppressive microenvironment in breast cancer.

    abstract::Rationale: Tumor microenvironment interacts with tumor cells to regulate their stemness properties through various cytokines and cytokine receptors. Previous studies revealed the possible role of interleukin 20 receptor subunit alpha (IL20RA) signaling in the progression of several types of tumors. However, its regula...


    pub_type: 杂志文章


    authors: Gao W,Wen H,Liang L,Dong X,Du R,Zhou W,Zhang X,Zhang C,Xiang R,Li N

    更新日期:2021-01-01 00:00:00

  • Retraction of "Novel Bioluminescent Activatable Reporter for Src Tyrosine Kinase Activity in Living Mice".

    abstract::[This retracts the article DOI: 10.7150/thno.14306.]. ...


    pub_type: 撤回出版物


    authors: Leng W,Li D,Chen L,Xia H,Tang Q,Chen B,Gong Q,Gao F,Bi F

    更新日期:2020-09-30 00:00:00

  • Pre-existing anti-polyethylene glycol antibody reduces the therapeutic efficacy and pharmacokinetics of PEGylated liposomes.

    abstract::Rationale: Increasing frequency of human exposure to PEG-related products means that healthy people are likely to have pre-existing anti-PEG antibodies (pre-αPEG Ab). However, the influence of pre-αPEG Abs on the pharmacokinetics (PK) and therapeutic efficacy of LipoDox is unknown. Methods: We generated two pre-αPEG A...


    pub_type: 杂志文章


    authors: Hsieh YC,Wang HE,Lin WW,Roffler SR,Cheng TC,Su YC,Li JJ,Chen CC,Huang CH,Chen BM,Wang JY,Cheng TL,Chen FM

    更新日期:2018-05-09 00:00:00

  • Multivalent Targeting Based Delivery of Therapeutic Peptide using AP1-ELP Carrier for Effective Cancer Therapy.

    abstract::Elastin-like polypeptide (ELP)-based drug delivery has been utilized for various applications including cancer therapies for many years. Genetic incorporation of internalization ligands and cell-targeting peptides along with ELP polymer enhanced tumor accumulation and retention time as well as stability and activities...


    pub_type: 杂志文章


    authors: Sarangthem V,Kim Y,Singh TD,Seo BY,Cheon SH,Lee YJ,Lee BH,Park RW

    更新日期:2016-09-25 00:00:00

  • Detection of high-risk atherosclerotic plaques with ultrasound molecular imaging of glycoprotein IIb/IIIa receptor on activated platelets.

    abstract:OBJECTIVE:Ultrasound molecular imaging (UMI) of glycoprotein (GP) IIb/IIIa receptor on activated platelets offers a unique means of identifying high-risk atherosclerosis. We hypothesized that contrast-enhanced ultrasound with microbubbles (MBs) targeted to GP IIb/IIIa could be used to detect and quantify activated plat...


    pub_type: 杂志文章


    authors: Guo S,Shen S,Wang J,Wang H,Li M,Liu Y,Hou F,Liao Y,Bin J

    更新日期:2015-02-05 00:00:00

  • Near-infrared fluorescence imaging in the largely unexplored window of 900-1,000 nm.

    abstract::Near-infrared (NIR) fluorescence imaging has relied on fluorophores that emit in the 700-900 nm NIR-Ia or 1,000-1,700 nm NIR-II window for generating deep-tissue images. Up until now, there have been few fluorophores developed for the 900-1,000 nm NIR-Ib window. This is largely because NIR-Ib light is thought to be st...


    pub_type: 杂志文章


    authors: Deng G,Li S,Sun Z,Li W,Zhou L,Zhang J,Gong P,Cai L

    更新日期:2018-07-16 00:00:00

  • Smooth muscle SIRT1 reprograms endothelial cells to suppress angiogenesis after ischemia.

    abstract::Objective: Vascular smooth muscle cells (VSMCs) undergo the phenotypic changes from contractile to synthetic state during vascular remodeling after ischemia. SIRT1 protects against stress-induced vascular remodeling via maintaining VSMC differentiated phenotype. However, the effect of smooth muscle SIRT1 on the functi...


    pub_type: 杂志文章


    authors: Dou YQ,Kong P,Li CL,Sun HX,Li WW,Yu Y,Nie L,Zhao LL,Miao SB,Li XK,Dong C,Zhang JW,Liu Y,Huo XX,Chi K,Gao X,Zhang N,Weng L,Yang H,Zhang F,Han M

    更新日期:2020-01-01 00:00:00

  • Aptamer-Based Therapeutic Approaches to Target Cancer Stem Cells.

    abstract::Cancer stem cells (CSCs) are believed to be a principal cellular source for tumour progression and therapeutic drug resistance as they are capable of self-renewal and can differentiate into cancer cells. Importantly, CSCs acquire the ability to evade the killing effects of cytotoxic agents through changes at the genet...


    pub_type: 杂志文章,评审


    authors: Zhou G,Latchoumanin O,Bagdesar M,Hebbard L,Duan W,Liddle C,George J,Qiao L

    更新日期:2017-09-13 00:00:00

  • A new class of PentixaFor- and PentixaTher-based theranostic agents with enhanced CXCR4-targeting efficiency.

    abstract::Non-invasive PET imaging of CXCR4 expression in cancer and inflammation as well as CXCR4-targeted radioligand therapy (RLT) have recently found their way into clinical research by the development of the theranostic agents [68Ga]PentixaFor (cyclo(D-Tyr1-D-[NMe]Orn2(AMBS-[68Ga]DOTA)-Arg3-Nal4-Gly5) = [68Ga]DOTA-AMBS-CPC...


    pub_type: 杂志文章


    authors: Osl T,Schmidt A,Schwaiger M,Schottelius M,Wester HJ

    更新日期:2020-07-09 00:00:00

  • Modulation of Respiration and Mitochondrial Dynamics by SMAC-Mimetics for Combination Therapy in Chemoresistant Cancer.

    abstract::Inhibitor of apoptosis proteins (IAP) are cell death regulators that bind caspases and interfere with apoptotic signalling via death receptors or intrinsic cell death pathways. BIRC4/XIAP is the most potent anti-apoptotic IAP-member and it physically interacts with caspases via its BIR2 and its BIR3 domain. These doma...


    pub_type: 杂志文章


    authors: Hagenbuchner J,Oberacher H,Arnhard K,Kiechl-Kohlendorfer U,Ausserlechner MJ

    更新日期:2019-07-09 00:00:00

  • Tumor-targeted Dual-modality Imaging to Improve Intraoperative Visualization of Clear Cell Renal Cell Carcinoma: A First in Man Study.

    abstract::Intraoperative imaging with antibodies labeled with both a radionuclide for initial guidance and a near-infrared dye for adequate tumor delineation may overcome the main limitation of fluorescence imaging: the limited penetration depth of light in biological tissue. In this study, we demonstrate the feasibility and sa...


    pub_type: 杂志文章


    authors: Hekman MC,Rijpkema M,Muselaers CH,Oosterwijk E,Hulsbergen-Van de Kaa CA,Boerman OC,Oyen WJ,Langenhuijsen JF,Mulders PF

    更新日期:2018-03-08 00:00:00

  • Long Non-coding MIR205HG Depletes Hsa-miR-590-3p Leading to Unrestrained Proliferation in Head and Neck Squamous Cell Carcinoma.

    abstract::Over 70% of head & neck squamous cell carcinoma (HNSCC) patients carry TP53 oncogenic mutations. Here we studied the role of specific tumor-derived mutant p53 proteins in the aberrant transcription of long non-coding (lnc) MIR205HG gene in head and neck cancer cells. Methods: To understand the role of lncMIR205HG, tha...


    pub_type: 杂志文章


    authors: Di Agostino S,Valenti F,Sacconi A,Fontemaggi G,Pallocca M,Pulito C,Ganci F,Muti P,Strano S,Blandino G

    更新日期:2018-02-12 00:00:00

  • In vivo [64Cu]CuCl2 PET imaging reveals activity of Dextran-Catechin on tumor copper homeostasis.

    abstract::Given the strong clinical evidence that copper levels are significantly elevated in a wide spectrum of tumors, copper homeostasis is considered as an emerging target for anticancer drug design. Monitoring copper levels in vivo is therefore of paramount importance when assessing the efficacy of copper-targeting drugs. ...


    pub_type: 杂志文章


    authors: Parmar A,Pascali G,Voli F,Lerra L,Yee E,Ahmed-Cox A,Kimpton K,Cirillo G,Arthur A,Zahra D,Rahardjo G,Liu GJ,Lengkeek N,Saletta F,Charil A,Kavallaris M,Vittorio O

    更新日期:2018-11-09 00:00:00

  • Signal amplification and quantification on lateral flow assays by laser excitation of plasmonic nanomaterials.

    abstract::Lateral flow assay (LFA) has become one of the most widely used point-of-care diagnostic methods due to its simplicity and low cost. While easy to use, LFA suffers from its low sensitivity and poor quantification, which largely limits its applications for early disease diagnosis and requires further testing to elimina...


    pub_type: 杂志文章,评审


    authors: Ye H,Liu Y,Zhan L,Liu Y,Qin Z

    更新日期:2020-03-15 00:00:00

  • Site-Specific Drug-Releasing Polypeptide Nanocarriers Based on Dual-pH Response for Enhanced Therapeutic Efficacy against Drug-Resistant Tumors.

    abstract::To enhance effective drug accumulation in drug-resistant tumors, a site-specific drug-releasing polypeptide system (PEG-Phis/Pasp-DOX/CA4) was exploited in response to tumor extracellular and intracellular pH. This system could firstly release the embedded tumor vascular inhibitor (CA4) to transiently 'normalize' vasc...


    pub_type: 杂志文章


    authors: Dong Y,Yang J,Liu H,Wang T,Tang S,Zhang J,Zhang X

    更新日期:2015-04-28 00:00:00

  • Type H blood vessels in bone modeling and remodeling.

    abstract::In the mammalian skeletal system, osteogenesis and angiogenesis are intimately linked during bone growth and regeneration in bone modeling and during bone homeostasis in bone remodeling. Recent studies have expanded our knowledge about the molecular and cellular mechanisms responsible for coupling angiogenesis and bon...


    pub_type: 杂志文章,评审


    authors: Peng Y,Wu S,Li Y,Crane JL

    更新日期:2020-01-01 00:00:00

  • Integrin targeted delivery of radiotherapeutics.

    abstract::Targeted radionuclide therapy, which is based on the selective delivery of a sufficient radiation dose to tumors without significantly affecting normal tissues, is a promising therapeutic approach for the treatment of a wide variety of malignancies. Integrins, a family of cell adhesion molecules, play key roles during...


    pub_type: 杂志文章


    authors: Liu Z,Wang F,Chen X

    更新日期:2011-03-01 00:00:00

  • General Anesthesia Inhibits the Activity of the "Glymphatic System".

    abstract::INTRODUCTION: According to the "glymphatic system" hypothesis, brain waste clearance is mediated by a continuous replacement of the interstitial milieu by a bulk flow of cerebrospinal fluid (CSF). Previous reports suggested that this cerebral CSF circulation is only active during general anesthesia or sleep, an effect...


    pub_type: 杂志文章


    authors: Gakuba C,Gaberel T,Goursaud S,Bourges J,Di Palma C,Quenault A,Martinez de Lizarrondo S,Vivien D,Gauberti M

    更新日期:2018-01-01 00:00:00

  • Preparation of quantum dot/drug nanoparticle formulations for traceable targeted delivery and therapy.

    abstract::Quantum dots (QDs) are luminescent nanocrystals with rich surface chemistry and unique optical properties that make them useful as probes or carriers for traceable targeted delivery and therapy applications. QDs can be functionalized to target specific cells or tissues by conjugating them with targeting ligands. Recen...


    pub_type: 杂志文章


    authors: Yong KT,Wang Y,Roy I,Rui H,Swihart MT,Law WC,Kwak SK,Ye L,Liu J,Mahajan SD,Reynolds JL

    更新日期:2012-01-01 00:00:00

  • Longitudinal monitoring of stem cell grafts in vivo using magnetic resonance imaging with inducible maga as a genetic reporter.

    abstract:PURPOSE:The ability to longitudinally monitor cell grafts and assess their condition is critical for the clinical translation of stem cell therapy in regenerative medicine. Developing an inducible genetic magnetic resonance imaging (MRI) reporter will enable non-invasive and longitudinal monitoring of stem cell grafts ...


    pub_type: 杂志文章


    authors: Cho IK,Moran SP,Paudyal R,Piotrowska-Nitsche K,Cheng PH,Zhang X,Mao H,Chan AW

    更新日期:2014-07-27 00:00:00

  • Triple-Modal Imaging of Magnetically-Targeted Nanocapsules in Solid Tumours In Vivo.

    abstract::Triple-modal imaging magnetic nanocapsules, encapsulating hydrophobic superparamagnetic iron oxide nanoparticles, are formulated and used to magnetically target solid tumours after intravenous administration in tumour-bearing mice. The engineered magnetic polymeric nanocapsules m-NCs are ~200 nm in size with negative ...


    pub_type: 杂志文章


    authors: Bai J,Wang JT,Rubio N,Protti A,Heidari H,Elgogary R,Southern P,Al-Jamal WT,Sosabowski J,Shah AM,Bals S,Pankhurst QA,Al-Jamal KT

    更新日期:2016-01-01 00:00:00

  • Spectroscopic Photoacoustic Molecular Imaging of Breast Cancer using a B7-H3-targeted ICG Contrast Agent.

    abstract::Purpose: Breast cancer imaging methods lack diagnostic accuracy, in particular for patients with dense breast tissue, and improved techniques are critically needed. The purpose of this study was to evaluate antibody-indocyanine green (ICG) conjugates, which undergo dynamic absorption spectrum shifts after cellular end...


    pub_type: 杂志文章


    authors: Wilson KE,Bachawal SV,Abou-Elkacem L,Jensen K,Machtaler S,Tian L,Willmann JK

    更新日期:2017-04-03 00:00:00

  • Critical reviews of immunotheranostics.

    abstract::Immunity is the most critical and well-regulated protection to the body. Immunity is implicated in a wide range of diseases and serves as the foundation for immunotherapy. Immunotheranostics is the idea of improving immunotherapy through the organic integration of therapeutic, diagnostic, and screening technologies. T...


    pub_type: 社论


    authors: Chen X,Chen M

    更新日期:2020-06-11 00:00:00