Immunohistochemical expression of erbb2 in adamantinomatous craniopharyngiomas: a possible target for immunotherapy

Zuhur, Sayid Shafi; Tanık, Canan; Erol, Rumeysa Selvinaz; Müslüman, Ahmet Murat; Kabukçuoğlu, Fevziye

doi:10.5137/1019-5149.jtn.6706-12.1

Cited by 7 publications

(5 citation statements)

References 28 publications

(31 reference statements)

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“…Other malignant solid tumors with HER2 overexpression include ovarian cancer, non small cell lung cancer, prostate cancer, gastric cancer, colorectal cancer, renal cell carcinoma, and bladder cancer (4)(5)(6). HER2 is a significant target for cancer therapy (7)(8)(9)(10). Herceptin (trastuzumab) is a humanized monoclonal antibody targeting HER2 and is widely used for the treatment of HER2-positive breast cancer.…”

Section: Introductionmentioning

confidence: 99%

The Third Generation Anti-HER2 Chimeric Antigen Receptor Mouse T Cells Alone or Together With Anti-PD1 Antibody Inhibits the Growth of Mouse Breast Tumor Cells Expressing HER2 in vitro and in Immune Competent Mice

Yang

et al. 2020

Front. Oncol.

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Chimeric Antigen Receptor (CAR)-T cells have great efficacy against CD19 + leukemia but little success for solid tumors. This study explored the effectiveness of third generation anti-HER2 CAR-T cells alone or in combination with anti-PD1 antibody on breast tumor cells expressing HER2 in vitro and in immune competent mouse model. The PDL1-positive mouse mammary tumor cell line 4T1 engineered to express luciferase and human HER2 was used as the target cell line (4T1-Luc-HER2). Anti-HER2 CAR-T cells were generated by transducing mouse spleen T cells with recombinant lentiviruses. ELISA analysis showed that IL-2 and IFN-γ secretion was increased in CAR-T cells co-cultured with the target cells, and the secretion of these two cytokines was increased further with the addition of anti-PD1 antibody. Lactate dehydrogenase assay revealed that CAR-T cells displayed a potent cytotoxicity against the target cells, and the addition of anti-PD1 antibody further enhanced the cytotoxicity. At the effector: target ratio of 16:1, cytotoxicity was 39.8% with CAR-T cells alone, and increased to 49.5% with the addition of anti-PD1 antibody. In immune competent syngeneic mouse model, CAR-T cells were found to be present in tumor stroma, inhibited tumor growth and increased tumor apoptosis significantly. Addition of anti-PD1 antibody further enhanced these anti-tumor activities. Twenty-one days after treatment, tumor weight was reduced by 50.0% and 73.3% in CAR-T group and CAR-T plus anti-PD1 group compared with blank T group. Our results indicate that anti-PD1 antibody can greatly increase the efficacy of anti-HER2 CAR-T against HER2-positive solid tumors.

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Section: Introductionmentioning

confidence: 99%

The Third Generation Anti-HER2 Chimeric Antigen Receptor Mouse T Cells Alone or Together With Anti-PD1 Antibody Inhibits the Growth of Mouse Breast Tumor Cells Expressing HER2 in vitro and in Immune Competent Mice

Yang

et al. 2020

Front. Oncol.

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“…9,11,12,24,28,38 As a result of this mechanism, nuclear accumulation of b-catenin is a histological hallmark of CTNNB1 mutation. 10,12,16,26,41 In the case of craniopharyngiomas, mutation of CTNNB1 has been described in 69%-100% 9,20,28 of ACP specimens, while it is not routinely observed in PCP or other parasellar tumors. 9,28 In the most detailed study to date, CTNNB1 mutation was identified in 95% of ACP specimens, using massively parallel sequencing and targeted genotyping.…”

Section: Ctnnb1 Mutationmentioning

confidence: 99%

“…10,32 This protein plays a critical role in development, cellular proliferation, differentiation, and cell migration. 10,11,16,41 A destruction complex restrains b-catenin within the cytosol and facilitates its ubiquitination and proteasomal degradation. 31 The Wnt protein family includes approximately 20 different proteins that bind to the Frizzled (Fz) family of receptors.…”

mentioning

confidence: 99%

Potential evolution of neurosurgical treatment paradigms for craniopharyngioma based on genomic and transcriptomic characteristics

Robinson

Santagata

Hankinson

2016

FOC

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The recent genomic and transcriptomic characterization of human craniopharyngiomas has provided important insights into the pathogenesis of these tumors and supports that these tumor types are distinct entities. Critically, the insights provided by these data offer the potential for the introduction of novel therapies and surgical treatment paradigms for these tumors, which are associated with high morbidity rates and morbid conditions. Mutations in the CTNNB1 gene are primary drivers of adamantinomatous craniopharyngioma (ACP) and lead to the accumulation of β-catenin protein in a subset of the nuclei within the neoplastic epithelium of these tumors. Dysregulation of epidermal growth factor receptor (EGFR) and of sonic hedgehog (SHH) signaling in ACP suggest that paracrine oncogenic mechanisms may underlie ACP growth and implicate these signaling pathways as potential targets for therapeutic intervention using directed therapies. Recent work shows that ACP cells have primary cilia, further supporting the potential importance of SHH signaling in the pathogenesis of these tumors. While further preclinical data are needed, directed therapies could defer, or replace, the need for radiation therapy and/or allow for less aggressive surgical interventions. Furthermore, the prospect for reliable control of cystic disease without the need for surgery now exists. Studies of papillary craniopharyngioma (PCP) are more clinically advanced than those for ACP. The vast majority of PCPs harbor the BRAFv600e mutation. There are now 2 reports of patients with PCP that had dramatic therapeutic responses to targeted agents. Ongoing clinical and research studies promise to not only advance our understanding of these challenging tumors but to offer new approaches for patient management.

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“…Mutation in exon 3 of CTNNB1, leading to overactivation of the Wnt/b-catenin signaling pathway, is considered the main oncogenic driver of ACP tumorigenesis. Moreover, other pathways, such as ERBB2 and SHH signaling, have also been shown to be related to tumor growth and proliferation (6)(7)(8). Gaston et al constructed an ACP embryonic and inducible model to further confirm that cells in the b-catenin-accumulating cluster promote tumor growth by regulating paracrine cells with a series of related proteins, including bone morphogenic proteins (BMPs) and fibroblast growth factors (FGFs) (9,10).…”

Section: Introductionmentioning

confidence: 99%

Identification and Characterization of TF-lncRNA Regulatory Networks Involved in the Tumorigenesis and Development of Adamantinomatous Craniopharyngioma

Guo

Lei

et al. 2022

Front. Oncol.

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Craniopharyngiomas (CPs) are rare tumors arising from the sellar region. Although the best outcome for patients with one subtype, adamantinomatous craniopharyngioma (ACP), is obtained by gross total resection, little is known about the roles of long noncoding RNAs (lncRNAs) and transcription factors (TFs) in ACP tumorigenesis. In total, 12 human ACP and 5 control samples were subjected to transcriptome-level sequencing. We built an integrated algorithm for identifying lncRNAs and TFs regulating the CP-related pathway. Furthermore, ChIP-Seq datasets with binding domain information were used to further verify and identify TF-lncRNA correlations. RT–PCR and immunohistochemistry staining were performed to validate the potential targets. Five pathways associated with ACP were identified and defined by an extensive literature search. Based on the specific pathways and the whole gene expression profile, 266 ACP-related lncRNAs and 39 TFs were identified by our integrating algorithm. Comprehensive analysis of the ChIP-Seq datasets revealed that 29 TFs were targeted by 12000 lncRNAs in a wide range of tissues, including 161 ACP-related lncRNAs that were identified by the computational method. These 29 TFs and 161 lncRNAs, constituting 1004 TF-lncRNA pairs, were shown to potentially regulate different ACP-related pathways. A total of 232 TF-lncRNA networks were consequently established based on differential gene expression. Validation by RT–PCR and immunohistochemistry staining revealed positive expression of the ACP-related TFs E2F2 and KLF5 in ACP. Moreover, the expression of the lncRNA RP11-360P21.2 was shown to be upregulated in ACP tissues. In this study, we introduced an integrated algorithm for identifying lncRNAs and TFs regulating the ACP-related pathway. This is the first comprehensive study to systematically investigate the potential TF and lncRNA regulatory network in ACP. The resulting data serve as a valuable resource for understanding the mechanisms underlying ACP-related lncRNAs and TFs.

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Immunohistochemical expression of erbb2 in adamantinomatous craniopharyngiomas: a possible target for immunotherapy

Cited by 7 publications

References 28 publications

The Third Generation Anti-HER2 Chimeric Antigen Receptor Mouse T Cells Alone or Together With Anti-PD1 Antibody Inhibits the Growth of Mouse Breast Tumor Cells Expressing HER2 in vitro and in Immune Competent Mice

The Third Generation Anti-HER2 Chimeric Antigen Receptor Mouse T Cells Alone or Together With Anti-PD1 Antibody Inhibits the Growth of Mouse Breast Tumor Cells Expressing HER2 in vitro and in Immune Competent Mice

Potential evolution of neurosurgical treatment paradigms for craniopharyngioma based on genomic and transcriptomic characteristics

Identification and Characterization of TF-lncRNA Regulatory Networks Involved in the Tumorigenesis and Development of Adamantinomatous Craniopharyngioma

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