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    DRUG CLASS:

    Angiopoietin 1 inhibitor

    Related drugs:
    3ms
    A Phase 1 Trial of Trebananib, an Angiopoietin 1 and 2 Neutralizing Peptibody, Combined with Pembrolizumab in Patients with Advanced Ovarian and Colorectal Cancer. (PubMed, Cancer Immunol Res)
    After development of acquired resistance, biopsy of one patient's KRAS wild-type, ERBB2 amplified tumor showed a substantial decline in tumor-associated T cells and an increase in immunosuppressive intratumoral macrophages. Future studies are needed to carefully assess whether clinicogenomic features, such as lack of liver metastases, ERBB2 amplification, and left-sided tumors, can predict increased sensitivity to PD1 immunotherapy combinations.
    P1 data • Journal • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • POLE (DNA Polymerase Epsilon)
    |
    HER-2 amplification • POLE mutation • KRAS wild-type • RAS wild-type
    |
    Keytruda (pembrolizumab) • trebananib (AMG 386)
    5ms
    Platelet Angiopoietin-1 Protects Against Murine Models of Tumor Metastasis. (PubMed, Arterioscler Thromb Vasc Biol)
    Serum from Angpt1Plt KO mice increased endothelial permeability and reduced VE-cadherin expression at endothelial junctions compared with serum from control mice (Angpt1WT). Platelets provide an intravascular source of Angpt1 that restrains tumor metastasis by preserving the lung microvasculature to limit tumor cell extravasation.
    Preclinical • Journal
    |
    CDH5 (Cadherin 5)
    7ms
    Differential expression of angiogenesis-related genes 'VEGF' and 'angiopoietin-1' in metastatic and EMAST-positive colorectal cancer patients. (PubMed, Sci Rep)
    Yet, the generalization of in silico findings to EMAST+ colorectal cancer warrants future experimental investigations. In the end, this study proposes that the EMAST biomarker could serve as an additional perspective on CMS4 biology which is well-defined by activated angiogenesis and worse overall survival.
    Journal • Metastases
    |
    VEGFA (Vascular endothelial growth factor A) • STAT3 (Signal Transducer And Activator Of Transcription 3) • ANGPT2 (Angiopoietin 2) • MALAT1 (Metastasis associated lung adenocarcinoma transcript 1) • AFAP1-AS1 (AFAP1 Antisense RNA 1) • KCNQ1OT1 (KCNQ1 Opposite Strand/Antisense Transcript 1) • E2F1 (E2F transcription factor 1)
    |
    VEGFA expression • ANGPT2 expression
    9ms
    Pembrolizumab (Anti-PD-1) and AMG386 (Angiopoietin-2 (Ang-2) in Patients With Advanced Solid Tumor (clinicaltrials.gov)
    P1, N=60, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Aug 2024 --> Aug 2025 | Trial primary completion date: Feb 2024 --> Feb 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    BRAF (B-raf proto-oncogene)
    |
    BRAF V600E • BRAF V600 • BRAF V600K
    |
    Keytruda (pembrolizumab) • trebananib (AMG 386)
    11ms
    Angiopoietin-2 and the Vascular Endothelial Growth Factor Promote Migration and Invasion in Hepatocellular Carcinoma- and Intrahepatic Cholangiocarcinoma-Derived Spheroids. (PubMed, Biomedicines)
    Inhibitors targeting ANG-2 (Trebananib) and the VEGF (Bevacizumab) effectively blocked the migration ability of spheroids that had been stimulated with rh-ANG-2 and rh-VEGF. Overall, our findings highlight the critical role played by ANG-2 and the VEGF in enhancing the ability of HCC- and iCCA-derived spheroids to migrate and invade, which are key processes in cancer progression.
    Journal
    |
    VEGFA (Vascular endothelial growth factor A) • CDH1 (Cadherin 1) • VIM (Vimentin) • CDH2 (Cadherin 2)
    |
    Avastin (bevacizumab) • trebananib (AMG 386)
    1year
    Neoadjuvant trebananib plus paclitaxel-based chemotherapy for stage II/III breast cancer in the adaptively randomized I-SPY2 trial - Efficacy and biomarker discovery. (PubMed, Clin Cancer Res)
    The Ang/Tie2 axis inhibitor trebananib combined with standard neoadjuvant therapy increased estimated pCR rates across HR-negative and MP2 subtypes, with probabilities of superiority >90%. Further study of Ang/Tie2 receptor axis inhibitors in validated, biomarker-predicted sensitive subtypes is warranted.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • CD8 (cluster of differentiation 8)
    |
    HER-2 positive • HER-2 negative • HER-2 expression • CD8 expression
    |
    MammaPrint
    |
    Herceptin (trastuzumab) • paclitaxel • doxorubicin hydrochloride • cyclophosphamide • trebananib (AMG 386)
    over1year
    Angiopoietin-1 promotes triple-negative breast cancer cell proliferation by upregulating carboxypeptidase A4. (PubMed, Acta Biochim Biophys Sin (Shanghai))
    Mechanistically, ANG1 promotes TNBC by upregulating carboxypeptidase A4 (CPA4) expression. Overall, the ANG1-CPA4 axis can be a therapeutic target for TNBC.
    Journal
    over1year
    Vascular density and expression of vascular endothelial growth factor and angiopoietin-1 using immunofluorescence technique in patients with metastatic renal cell carcinoma treated with first-line sunitinib. (PubMed, J Cancer Res Ther)
    No abstract available
    Journal • Metastases
    |
    VEGFA (Vascular endothelial growth factor A)
    |
    VEGFA expression
    |
    sunitinib
    over1year
    Pembrolizumab (Anti-PD-1) and AMG386 (Angiopoietin-2 (Ang-2) in Patients With Advanced Solid Tumor (clinicaltrials.gov)
    P1, N=60, Active, not recruiting, Dana-Farber Cancer Institute | Trial primary completion date: Feb 2023 --> Feb 2024
    Trial primary completion date • Metastases
    |
    BRAF (B-raf proto-oncogene)
    |
    BRAF V600E • BRAF V600 • BRAF V600K
    |
    Keytruda (pembrolizumab) • trebananib (AMG 386)
    2years
    Baseline Systemic Inflammatory Markers Interleukin 6 and Ferritin Are Associated with Toxicities and Progression-Free Survival in Multiple Myeloma Patients Treated with Idecabtagene Vicleucel (ASH 2022)
    Recent studies found that elevated levels of cytokines and inflammatory markers pre-treatment are associated with severe toxicities in B cell lymphoma patients receiving axicabtagene ciloleucel...Tocilizumab and steroids were used in 79% and 32% of patients, respectively...Tailoring toxicity and additional therapeutic management to patient risk may mitigate morbidity and mortality.D.K.H. and L.C.P contributed equally; M.A. and M.L.D contributed equally
    Clinical
    |
    IFNG (Interferon, gamma) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • IL2 (Interleukin 2) • CSF2 (Colony stimulating factor 2) • IL15 (Interleukin 15) • CRP (C-reactive protein)
    |
    Yescarta (axicabtagene ciloleucel) • Actemra IV (tocilizumab) • Abecma (idecabtagene vicleucel)
    2years
    Intracellular angiopoietin-1 promotes TKI-resistance via activation of JAK/STAT5 pathway in chronic myeloid leukemia. (PubMed, Oncogene)
    Silencing ANG-1significantly sensitized three TKI-resistant CML cell lines to imatinib (IM) while recombinant human ANG-1 failed to retain cell survival in vitro...Upstream Src phosphorylation, which plays a crucial role in CML drug resistance, was also upregulated as a key event in iANG-1-related JAK/STAT pathway activation. In conclusion, our study elucidated a new BCR-ABL independent molecular mechanism induced by intracytoplasmic ANG-1 overexpression as a potential strategy for overcoming CML resistance.
    Journal • IO biomarker
    |
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • CD34 (CD34 molecule)
    |
    imatinib
    2years
    The molecular mechanisms underlying neutrophil infiltration in vessel co-opting colorectal cancer liver metastases. (PubMed, Front Oncol)
    Altogether, our data suggest the molecular mechanisms by which neutrophils are infiltrated in vessel co-opting CRCLM lesions. This finding may yield novel therapeutic strategies for CRCLM patients in future.
    Journal
    |
    RUNX1 (RUNX Family Transcription Factor 1)
    2years
    Identification of Evolutionary Mechanisms of Myelomatous Effusion By Single-Cell RNA Sequencing (ASH 2022)
    LILRB4 increased the mRNA expression of angiopoietin 1, integrin αv, and integrin β3, indicating LILRB4 may promoted PC invasion through integrin family. In conclusion, these data suggested EMICs and LILRB4 associated with extramedullary development and provided insight into evolutionary mechanisms of ME.
    PARP Biomarker
    |
    S100A8 (S100 Calcium Binding Protein A8) • MALAT1 (Metastasis associated lung adenocarcinoma transcript 1) • CASP3 (Caspase 3) • E2F1 (E2F transcription factor 1)
    2years
    Transplanted hair follicle mesenchymal stem cells alleviated small intestinal ischemia-reperfusion injury via intrinsic and paracrine mechanisms in a rat model. (PubMed, Front Cell Dev Biol)
    HFMSCs are beneficial to alleviate small intestinal IR injury through intrinsic homing to the small intestine and by differentiating into ISCs, via a paracrine mechanism to promote angiogenesis, reduce apoptosis, regulate the oxidative stress response, and protect intestinal mucosal function potentially. Therefore, this study suggests that HFMSCs serve as a new option for the treatment of small intestinal IR injury.
    Preclinical • Journal • IO biomarker
    |
    BCL2 (B-cell CLL/lymphoma 2) • IGF1 (Insulin-like growth factor 1) • BAX (BCL2-associated X protein) • PCNA (Proliferating cell nuclear antigen)
    |
    BCL2 expression • BAX expression • PCNA expression
    2years
    DHX15 DEFICIENCY AFFECTS VASCULAR GROWTH AND IMPAIRS TUMOR PROGRESSION IN A MOUSE MODEL OF HEPATOCELLULAR CARCINOMA (AASLD 2022)
    DHX15 deficiency in Hepa 1-6 HCC model is associated with vascular alterations that impede proper vascular development in the primary tumor resulting in decreased primary tumor volume and reduced metastasis in the liver. Our findings reveal the regulatory function of DHX15 in controlling vascular organization, tumor growth and metastasis.
    Preclinical
    |
    FLT1 (Fms-related tyrosine kinase 1) • VEGFD (Vascular Endothelial Growth Factor D)
    |
    FLT1 expression
    2years
    TIE2-high cervical cancer cells promote tumor angiogenesis by upregulating TIE2 and VEGFR2 in endothelial cells. (PubMed, Transl Oncol)
    TIE2-high tumor cells induced an amplified expression of TIE2 and vascular endothelial growth factor receptor 2(VEGFR2) in HUVECs to promote angiogenesis via TIE2 -AKT/MAPK signals, which could be reversed or partially reversed by TIE2, AKT or MAPK inhibitors and activated by angiopoietin-1 and angiopoietin-2. In conclusion, TIE2-high cervical cancer cells promote tumor angiogenesis by upregulating TIE2 and VEGFR2 in endothelial cells via TIE2-AKT/MAPK axis inside tumor cells.
    Journal
    |
    KDR (Kinase insert domain receptor)
    2years
    Combined treatment of marizomib and cisplatin modulates cervical cancer growth and invasion and enhances antitumor potential in vitro and in vivo. (PubMed, Front Oncol)
    The results suggest that Mzb has better antitumor effects on cervical cancer cells and can sensitize cervical cancer cells to CDDP treatment both in vitro and in vivo. Accordingly, we conclude that the combination of CDDP with Mzb produces synergistic anticancer activity and that Mzb may be a potential effective drug in combination therapy for cervical cancer patients.
    Preclinical • Journal
    |
    FLT3 (Fms-related tyrosine kinase 3)
    |
    cisplatin • marizomib (NPI-0052)
    over2years
    Arsenic trioxide inhibits angiogenesis of hepatocellular carcinoma after insufficient radiofrequency ablation via blocking paracrine angiopoietin-1 and angiopoietin-2. (PubMed, Int J Hyperthermia)
    ATO inhibited tumor growth and angiogenesis in HCC after insufficient RFA. Our results demonstrate that ATO blocks the paracrine signaling of Ang-1 and Ang-2 by inhibiting p-Akt/Hif-1α and further suppresses the angiogenesis of HCC after insufficient RFA.
    Journal
    |
    HIF1A (Hypoxia inducible factor 1, alpha subunit)
    |
    HIF1A overexpression • HIF1A expression
    |
    arsenic trioxide
    over2years
    Prognostic and predictive significance of VEGF, CD31, and Ang-1 in patients with metastatic clear cell renal cell carcinoma treated with first-line sunitinib. (PubMed, Bosn J Basic Med Sci)
    The expression of biomarkers in normal kidney tissue was significantly lower than in tumor tissue (p<0.001). In conclusion, higher VEGF scores and greater CD31 expression were associated with longer DFS, but neither of these biomarkers correlated with progression-free survival or overall survival.
    Journal
    |
    VEGFA (Vascular endothelial growth factor A) • CD31 (Platelet and endothelial cell adhesion molecule 1)
    |
    CD31 expression • VEGFA expression
    |
    sunitinib
    over2years
    Increasing angiotensin-converting enzyme (ACE) 2/ACE axes ratio alleviates early pulmonary vascular remodeling in a porcine model of acute pulmonary embolism with cardiac arrest. (PubMed, World J Emerg Med)
    Increasing the ACE2/ACE axes ratio may ameliorate pulmonary arterial remodeling by inhibiting the apoptosis and proliferation of endothelial cells after ROSC induced by APE.
    Preclinical • Journal • IO biomarker
    |
    BCL2 (B-cell CLL/lymphoma 2) • CASP3 (Caspase 3)
    |
    VEGFA expression
    |
    captopril
    over2years
    Molecular subtype to predict pathologic complete response in HER2-positive breast cancer in the I-SPY2 trial. (ASCO 2022)
    P2 | "The I-SPY2 platform trial tests novel agents given neoadjuvantly with a backbone of taxol (T) and trastuzumab (H) followed by doxorubicin and cyclophosphamide. Agents investigated in HER2+ bc were TH (control), MK2206, AMG386, pertuzumab (P), neratinib (N (given in place of H), and TDM1+P (given in place of TH)... pCR rates for patients with HER2+ bc treated with investigational agents, particularly dual HER2-blockade, were promising. Molecular response predictive subtype classification provides insight on how to better target therapy. The HER2+/Luminal group had low pCR rates with dual HER2-blockade but may have higher pCR rate with the addition of an AKT inhibitor and identifies a subgroup of HER2+ tumors in need of novel approaches."
    Clinical
    |
    HER-2 (Human epidermal growth factor receptor 2) • DRD (DNA Repair Deficiency)
    |
    HER-2 positive • DDR • DRD
    |
    paclitaxel • Nerlynx (neratinib) • Perjeta (pertuzumab) • doxorubicin hydrochloride • cyclophosphamide • MK-2206 • trebananib (AMG 386)
    almost3years
    Pan-cancer-specific engineered oncolytic vaccinia virus (AACR 2022)
    Meanwhile, treatment with the conventional anti-cancer drug cisplatin did not induce apoptosis. A virus-treated mouse colon/lung cancer syngeneic model showed attenuated tumor growth, which was in accordance with the results of percent survival measurement, CD8 expression analysis, and TUNEL staining with advanced genetic engineering. Taken together, our results indicate that NOV induces cancer tissue apoptosis and anti-tumor immunity and may constitute a highly advantageous therapeutic agent for next-generation solid tumor virotherapy with pan-cancer-specific oncolytic activity and high biosafety.
    Oncolytic virus • Pan tumor
    |
    CD8 (cluster of differentiation 8)
    |
    CD8 expression
    |
    cisplatin
    almost3years
    Immune-related gene ANGPT1 is an adverse biomarker for endometrial carcinoma. (PubMed, Transl Cancer Res)
    A high-infiltrating regulatory T cell would improve the prognosis for EC patients. The gene ANGPT1 can increase the infiltration of T cells and improve the prognosis of EC patients.
    Journal • IO biomarker
    |
    CD4 (CD4 Molecule)
    almost3years
    Diagnostic and Prognostic Utility of the Extracellular Vesicles Subpopulations Present in Pleural Effusion. (PubMed, Biomolecules)
    The corresponding ratios of Mesothelin, Galectin-1, Osteopontin, and VEGF were higher in MPM effusions compared to those in the benign group. These findings demonstrate that relevant diagnostic markers can be recovered from exosomes.
    Clinical • Journal • Pleural effusion
    |
    VEGFA (Vascular endothelial growth factor A) • MSLN (Mesothelin) • SPP1 (Secreted Phosphoprotein 1) • LGALS1 (Galectin 1)
    3years
    MALAT1 Improves Functional Recovery after Traumatic Brain Injury through Promoting Angiogenesis in Experimental Mice. (PubMed, Brain Res)
    MALAT1 could promote angiogenesis, subsequently contributing to the Ang1 synthesis from active vasculature. It may eventually benefit to functional recovery following TBI.
    Preclinical • Journal
    |
    MALAT1 (Metastasis associated lung adenocarcinoma transcript 1)
    3years
    PHASE II TRIAL OF VACCINE IMMUNOTHERAPY IN PRIMARY GLIOBLASTOMA: ADJUNCTIVE AUTOLOGOUS DENDRITIC CELLS PULSED WITH LYSATE FROM IRRADIATED SELF-RENEWING AUTOLOGOUS TUMOR CELLS (AV-GBM-1) (SNO 2021)
    feasibility, safety, and PFS were encouraging. A phase III trial is in development. Clinicaltrials.gov NCT03400917.
    P2 data • IO biomarker
    |
    MGMT (6-O-methylguanine-DNA methyltransferase) • CSF2 (Colony stimulating factor 2) • FGF (Fibroblast Growth Factor) • LCN2 (Lipocalin-2) • IL4 (Interleukin 4)
    |
    AV-GBM-1
    3years
    Long Non-coding RNA Rhabdomyosarcoma 2-Associated Transcript Regulates Angiogenesis in Endothelial Cells. (PubMed, Front Physiol)
    We conclude that RMST is expressed in human ECs and that this expression is upregulated in response to hypoxia and during differentiation into capillary-like structures. We also conclude that RMST plays important roles in EC survival and migration.
    Journal
    |
    FGF2 (Fibroblast Growth Factor 2)
    over3years
    RNA-binding protein SAMD4A inhibits breast tumor angiogenesis by modulating the balance of angiogenesis program. (PubMed, Cancer Sci)
    Mechanistically, SAMD4A was found to specifically destabilize the proangiogenic gene transcripts, including C-X-C motif chemokine ligand 5 (CXCL5), endoglin (ENG), interleukin 1β (IL1β), and angiopoietin 1 (ANGPT1), by directly interacting with the stem-loop structure in the 3' untranslated region (3'UTR) of these mRNAs through its Sterile Alpha Motif (SAM) domain, resulting in the imbalance of angiogenic genes expression. Collectively, our results suggest that SAMD4A is a novel breast tumor suppressor that inhibits tumor angiogenesis by specifically downregulating the expression of proangiogenic genes, which might be a potential anti-angiogenic target for breast cancer therapy.
    Journal
    |
    CXCL5 (Chemokine (C-X-C motif) ligand 5) • ENG (Endoglin) • IL1B (Interleukin 1, beta)
    over3years
    I-SPY 2: I-SPY TRIAL: Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer (clinicaltrials.gov)
    P2; Trial completion date: Dec 2026 --> Dec 2031 | Trial primary completion date: Dec 2025 --> Dec 2030
    Trial completion date • Trial primary completion date • Clinical
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • ER negative
    |
    TargetPrint®
    |
    Keytruda (pembrolizumab) • Herceptin (trastuzumab) • Lynparza (olaparib) • carboplatin • Imfinzi (durvalumab) • Nerlynx (neratinib) • Perjeta (pertuzumab) • Kadcyla (ado-trastuzumab emtansine) • doxorubicin hydrochloride • Talzenna (talazoparib) • Verzenio (abemaciclib) • cyclophosphamide • irinotecan • Jemperli (dostarlimab-gxly) • Tukysa (tucatinib) • letrozole • veliparib (ABT-888) • Libtayo (cemiplimab-rwlc) • MK-2206 • ganitumab (AMG 479) • amcenestrant (SAR439859) • metformin • Jivadco (trastuzumab duocarmazine) • Turalio (pexidartinib) • ganetespib (ADX-1612) • Cosela (trilaciclib) • fianlimab (REGN3767) • Oraxol (oral paclitaxel/encequidar) • ladiratuzumab vedotin (SGN-LIV1A) • nelitolimod (SD-101) • patritumab (U3-1287) • trebananib (AMG 386)
    over3years
    Prognostic role of plasma level of angiopoietin-1, angiopoietin-2, and vascular endothelial growth factor in hepatocellular carcinoma. (PubMed, World J Gastroenterol)
    The plasma levels of Ang-2 correlated with liver function, tumor stage, and tumor invasiveness, showing better performance in predicting OS and PFS than AFP, Ang-1, or VEGF.
    Journal
    |
    VEGFA (Vascular endothelial growth factor A) • AFP (Alpha-fetoprotein)
    over3years
    CD44 Sorted Cells Have an Augmented Potential for Proliferation, Epithelial-Mesenchymal Transition, Stemness, and a Predominantly Inflammatory Cytokine and Angiogenic Secretome. (PubMed, Curr Issues Mol Biol)
    The CD44+ CSCs cells demonstrated significant increased levels of EMT-related genes TWIST1 and CDH2 (N-cadherin), CSC-related genes CD44 and CD133 (PROM1), stemness-related genes OCT4, SOX2, inflammatory cytokines IL-1ß, IL-12, IL-18 and TNF-α and angiogenic factors Angiopoietin-1, Angiopoietin-2, bFGF and VEGF while levels of epithelial gene CDH1 (E-cadherin) decreased in comparison to mixed cell population. The genetic and secretome profiling of the CD44+ CSCs could serve as diagnostic and prognostic tools in the treatment of oral cancers.
    Journal
    |
    TNFA (Tumor Necrosis Factor-Alpha) • CDH1 (Cadherin 1) • CD44 (CD44 Molecule) • SOX2 • POU5F1 (POU Class 5 Homeobox 1) • IL18 (Interleukin 18) • CDH2 (Cadherin 2)
    |
    CD44 expression
    over3years
    Exosomes from cervical cancer cells facilitate pro-angiogenic endothelial reconditioning through transfer of Hedgehog-GLI signaling components. (PubMed, Cancer Cell Int)
    Overall, the data showed cervical cancer exosomes promote pro-angiogenic response in endothelial cells via upregulation of Hh-GLI signaling and modulate downstream angiogenesis-related target genes. The study provides a novel exosome-mediated mechanism potentially favoring cervical angiogenesis and thus identifies the exosomes as potential pharmacological targets against locally-advanced metastatic cervical lesions.
    Journal
    |
    KDR (Kinase insert domain receptor) • PTCH1 (Patched 1) • SPP1 (Secreted Phosphoprotein 1) • GLI1 (GLI Family Zinc Finger 1) • VEGFB (Vascular Endothelial Growth Factor B)
    |
    KDR expression • VEGFA expression
    over3years
    Mitofusin-2 is a novel anti-angiogenic factor in pancreatic cancer. (PubMed, J Gastrointest Oncol)
    Additionally, MFN2 overexpression enhanced the protein expression of p21 and p27 while attenuating the expression of proliferating cell nuclear antigen, VEGFA, VEGFR2, ANGPT1, and TIPM1 in HUVECs. In conclusion, MFN2 expression negatively correlates with VEGFA expression in PC and inhibits endothelial cell growth and angiogenesis.
    Journal
    |
    KDR (Kinase insert domain receptor) • TIMP1 (Tissue inhibitor of metalloproteinases 1) • PCNA (Proliferating cell nuclear antigen) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
    |
    VEGFA expression • KIM1 expression • TIMP1 expression • CDKN1B expression
    over3years
    Oligodendrocyte precursor cell specification is regulated by bidirectional neural progenitor-endothelial cell crosstalk. (PubMed, Nat Neurosci)
    Endothelial-derived TGFβ1, in turn, acts as an angiocrine molecule and signals back to NPCs to induce their commitment toward oligodendrocyte precursor cells. This work demonstrates a true bidirectional collaboration between NPCs and the vasculature as a critical regulator of oligodendrogenesis.
    Journal
    |
    TGFB1 (Transforming Growth Factor Beta 1)
    over3years
    Extracellular vesicles shed by follicular lymphoma B cells promote the polarization of bone marrow stromal cell niche. (PubMed, Blood)
    Moreover, we provided the first characterization of BM FL B-cell GEP, allowing the definition of the landscape of molecular interactions they could engage with EV-primed BM-MSC. This work identified FL-derived EVs as putative mediators of BM stroma polarization and supported further investigation of their clinical interest for targeting the crosstalk between BM-MSC and malignant B cells.
    Journal
    |
    CXCL12 (C-X-C Motif Chemokine Ligand 12)
    over3years
    Exosomal miR-3682-3p Suppresses Angiogenesis by Targeting ANGPT1 via the RAS-MEK1/2-ERK1/2 Pathway in Hepatocellular Carcinoma. (PubMed, Front Cell Dev Biol)
    By in vitro gain-of-function experiments, we found that HCC cells secreted exosomal miR-3682-3p, which negatively regulates angiopoietin-1 (ANGPT1), and this led to inhibition of RAS-MEK1/2-ERK1/2 signaling in endothelial cells and eventually impaired angiogenesis. Our study elucidates that exosomal miR-3682-3p attenuates angiogenesis by targeting ANGPT1 through RAS-MEK1/2-ERK1/2 signaling and provides novel potential targets for liver cancer therapy.
    Journal
    |
    MAP2K1 (Mitogen-activated protein kinase kinase 1)
    over3years
    Gene expression in the angiopoietin/TIE axis is altered in peripheral tissue of ovarian cancer patients: A prospective observational study. (PubMed, Life Sci)
    Altered expression of barrier dysfunction- and angiogenesis-associated genes from the ANG/TIE axis was detected not only in tumor but also in peripheral tissues of cancer patients. This may contribute to a systemic vascular leakage-related genotype.
    Clinical • Observational data • Journal
    |
    KDR (Kinase insert domain receptor) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • FLT1 (Fms-related tyrosine kinase 1) • ICAM1 (Intercellular adhesion molecule 1) • CCL2 (Chemokine (C-C motif) ligand 2) • VCAM1 (Vascular Cell Adhesion Molecule 1)
    |
    FLT1 expression
    over3years
    Interleukin-6 as an enhancer of anti-angiogenic therapy for ovarian clear cell carcinoma. (PubMed, Sci Rep)
    Although bevacizumab (Bev) is a widely used anti-angiogenic agent for EOC, the efficacy of Bev and the role of IL-6 in modulating angiogenesis in OCCC are unknown. We performed tube formation assays using human umbilical vein endothelial cells (HUVEC) cultured in OCCC cell-conditioned medium and using cells directly co-cultured with OCCC cells...Finally, depletion of Ang1 abrogated the effects of IL-6 inhibition on Bev activity, demonstrating that IL-6 supports the anti-angiogenic activity of Bev by suppressing Ang1 expression and promoting dependence on VEGF for angiogenesis. Altogether, our data suggest that OCCC tumors with high IL-6 levels are candidates for Bev therapy.
    Journal
    |
    IL6 (Interleukin 6)
    |
    IL6 elevation
    |
    Avastin (bevacizumab)
    almost4years
    Pembrolizumab (Anti-PD-1) and AMG386 (Angiopoietin-2 (Ang-2) in Patients With Advanced Solid Tumor (clinicaltrials.gov)
    P1, N=60, Active, not recruiting, Dana-Farber Cancer Institute | Recruiting --> Active, not recruiting | Trial primary completion date: Dec 2020 --> Feb 2023
    Clinical • Enrollment closed • Trial primary completion date
    |
    BRAF (B-raf proto-oncogene)
    |
    BRAF V600E • BRAF V600 • BRAF V600K
    |
    Keytruda (pembrolizumab) • trebananib (AMG 386)
    almost4years
    Elevated Secretion of Aldosterone Increases TG/HDL-C Ratio and Potentiates The Ox-LDL-Induced Dysfunction of HUVEC. (PubMed, Cell J)
    Elevated Aldo with high Ox-LDL together may accelerate the dysfunction of HUVEC, and the Ox-LDL, especially for those patients with high Aldo should be well controlled. The assessment of the role of Aldo may provide a theoretical basis for the effective prevention and investigation of a new treatment of AS.
    Journal
    |
    BCL2 (B-cell CLL/lymphoma 2) • NOS3 (Nitric oxide synthase 3) • SIRT1 (Sirtuin 1)