Last update 01 Nov 2024

HER2 x HLA-G

Last update 01 Nov 2024

Basic Info

Related Targets

HER2HLA-G

Drugs associated with HER2 x HLA-G

CN118420786

Patent Mining

Target

HER2 x HLA-G

Mechanism-

Active Org.

The First Affiliated Hospital,Zhejiang University School of Medicine

Originator Org.

The First Affiliated Hospital,Zhejiang University School of Medicine

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with HER2 x HLA-G

100 Translational Medicine associated with HER2 x HLA-G

0 Patents (Medical) associated with HER2 x HLA-G

Literatures (Medical) associated with HER2 x HLA-G

01 Nov 2020·Geburtshilfe und FrauenheilkundeQ4 · MEDICINE

HLA-J, a Non-Pseudogene as a New Prognostic Marker for Therapy Response and Survival in Breast Cancer

Q4 · MEDICINE

Article

Author: Zamagni, Claudio ; Würfel, Wolfgang ; Rübner, Matthias ; Winterhalter, Christoph ; Veltrup, Elke ; Santini, Donatella ; Taffurelli, Mario ; Wirtz, Ralph M. ; Mandrioli, Anna ; Fasching, Peter A. ; Würfel, Franziska M.

AbstractThe human leukocyte antigen (HLA) genes are cell-surface proteins, essential for immune cell interaction. HLA-G is known for their high immunosuppressive effect and its potential as predictive marker in breast cancer. However, nothing is known about the HLA-J and its immunosuppressive, prognostic and predictive features, as it is assumed to be a “pseudogene” by in silico sequence interpretation. HLA-J, ESR1, ERBB2, KRT5 and KRT20 mRNA expression were analysed in 29 fresh frozen breast cancer biopsies and their corresponding resectates obtained from patients treated with neoadjuvant chemotherapy (NACT). mRNA was analysed with gene specific TaqMan-based Primer/Probe sets and normalized to Calmodulin 2. All breast cancer samples did express HLA-J and frequently increased HLA-J mRNA levels after NACT. HLA-J mRNA was significantly associated with overexpression of the ESR1 mRNA status (Spearman ρ 0,5679; p = 0.0090) and KRT5 mRNA (Spearman ρ 0,6121; p = 0.0041) in breast cancer core biopsies and dominated in luminal B subtype. Kaplan Meier analysis revealed that an increase of HLA-J mRNA expression after NACT had worse progression free survival (p = 0,0096), indicating a counterreaction of tumor tissues presumably to prevent elimination by enhanced immune infiltration induced by NACT. This counterreaction is associated with worse prognosis. To our knowledge this is the first study identifying HLA-J as a new predictive marker in breast cancer being involved in immune evasion mechanisms.

01 Aug 2015·PlacentaQ3 · MEDICINE

ERBB2 gene amplification increases during the transition of proximal EGFR+ to distal HLA-G+ first trimester cell column trophoblasts

Q3 · MEDICINE

Article

Author: Kaltenberger, S ; Meinhardt, G ; Fiala, C ; Knöfler, M ; Pollheimer, J

INTRODUCTIONAlthough, DNA copy-number alterations (CNAs) have been well documented in a number of adverse phenotypic conditions, accumulating data suggest that CNAs also occur during physiological processes. Interestingly, extravillous trophoblasts induce the expression of the transforming, proto-oncogene ERBB2, which is frequently amplified in human cancer. However, no data are available to address whether trophoblast-related ERBB2 expression might also be linked to genomic amplification.METHODSDual color silver as well as fluorescence in situ hybridization analyses were carried out to evaluate frequency and degree of ERBB2 gene and chromosome 17 copy numbers in first trimester placental cell columns and isolated trophoblasts. Proliferative EGFR(+) and differentiated HLA-G(+) trophoblasts were identified or separated by means of in situ immunofluorescence co-stainings and magnetic beads cell isolation, respectively.RESULTSERBB2 gene amplification is detected in approximately 40% of isolated HLA-G(+) trophoblasts. Although already detectable in EGFR(+) cells, the percentage and extent of ERBB2 amplification was markedly increased in HLA-G(+) trophoblasts in situ and after isolation. Accordingly, HLA-G(+) trophoblasts highly express ERBB2 on protein level. Finally, ERBB2 copy number variations occur independently of aneuploidy as the majority of ERBB2 amplifying cells were cytogenetically diploid for chromosome 17.DISCUSSIONERBB2 gene amplification is a frequent event during EVT differentiation. This finding challenges the long standing paradigm, which associates gene amplification with pathological conditions and further supports recent evidences suggesting that CNAs are a normal feature of developmental processes.

01 Apr 2015·Human ReproductionQ1 · MEDICINE

Trophoblast subtype-specific EGFR/ERBB4 expression correlates with cell cycle progression and hyperplasia in complete hydatidiform moles

Q1 · MEDICINE

Article

Author: Milla, Stephanie K ; Plessl, Kerstin ; Pollheimer, Jürgen ; Haider, Sandra ; Fock, Valerie ; Fiala, Christian ; Dekan, Sabine ; Knöfler, Martin ; Fuchs, Roman

STUDY QUESTIONDo trophoblast subtypes differ in their expression of erythroblastic leukaemia viral oncogene homologue (ERBB) receptor family members and responsiveness towards specific growth factor ligands?SUMMARY ANSWEROur data reveal a reciprocal expression pattern of epidermal growth factor receptor (EGFR)/ERBB4 in proliferative and ERBB2/ERBB3 in invasive trophoblast subtypes, as well as a restricted responsiveness to epidermal growth factor (EGF) and heparin-binding (HB)-EGF.WHAT IS KNOWN ALREADYEGFR is expressed by villous cytotrophoblasts (vCTBs), but absent from extravillous trophoblasts (EVTs), which specifically up-regulate ERBB2.STUDY DESIGN, SIZE, DURATIONTissue samples of human first trimester placentae (n = 50) and deciduae (n = 5) obtained from elective pregnancy terminations were used to study trophoblast subtype-specific ERBB receptor expression and responsiveness to recombinant human EGF and HB-EGF. Age-matched complete hydatidiform mole (CHM) placentae (n = 12) were assessed for EGFR and ERBB4 expression in proliferation-competent regions.PARTICIPANTS/MATERIALS, SETTING, METHODSERBB receptor expression was analysed in primary trophoblast cell isolates by means of microarray, quantitative real-time PCR and western blotting, as well as immunofluorescence stainings of placental and decidual tissue sections. EGF and HB-EGF were tested for their potential to activate ERBB receptors in purified EGFR(+) and HLA-G(+) trophoblasts. 5-Ethynyl-2'-deoxyuridine incorporation assays were performed to study the effect of both ligands on the proliferative capacity of primary trophoblasts as well as of vCTBs and proximal cell column trophoblasts (pCCTs) in placental floating explants. Finally, the average number of EGFR(+) vCTB and pCCT layers was determined in CHM placentae and compared with healthy age-matched controls.MAIN RESULTS AND THE ROLE OF CHANCEProliferative vCTBs and pCCTs co-express EGFR and ERBB4, but are devoid of ERBB2 and ERBB3. In contrast, HLA-G(+) trophoblast subtypes exhibit an EGFR/ERBB4(-) and ERBB2/ERBB3(+) phenotype. EGF and HB-EGF activate EGFR, ERBB4, AKT and extracellular signal-regulated kinase 1/2 in EGFR(+) primary trophoblasts; however, they do not show an effect on HLA-G(+) EVTs. Both ligands strongly induce cell cycle progression in primary trophoblasts (P < 0.05) and placental explant-associated vCTBs (P < 0.05) and pCCTs (P < 0.05). Notably, EGFR(+) vCTB (P < 0.0001) and pCCT (P < 0.0001) layers are significantly expanded in CHM placentae when compared with healthy controls.LIMITATIONS, REASONS FOR CAUTIONCells were removed from their physiological context and may therefore respond differently to various stimuli.WIDER IMPLICATIONS OF THE FINDINGSIn this study we define EGFR as a marker for proliferative trophoblast subtypes within the human placenta. Manipulation of EGFR signalling might thus offer a promising therapeutic avenue for the treatment of molar pregnancies associated with trophoblast hyperplasia.STUDY FUNDING/COMPETING INTERESTSThis study was supported by the Austrian Science Fund (grant P-25187-B13 to J.P.). There are no competing interests to declare.

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