Circulating Natural Autoantibodies to HER2-Derived Peptides Performed Antitumor Effects on Oral Squamous Cell Carcinoma

Liu, Xiu; He, Zhong; Qu, Yi; Meng, Qingyong; Qin, Lizheng; Hu, Ying

doi:10.3389/fphar.2021.693989

Cited by 3 publications

(1 citation statement)

References 48 publications

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“…is result suggests that IVIG was able to inhibit the carcinogenic process of DEN to some extent and protected the liver. IVIG can effectively inhibit tumor proliferation, infiltration, and metastasis in tumor cell lines, tumor animal models, and tumor patients [5,6], such as oral squamous carcinoma [13], renal cell carcinoma [14], and breast cancer [15], but the antitumor mechanism of action of IVIG is not fully understood. e occurrence of hepatocellular carcinoma is a complicated process involving numerous factors and multiple pathways.…”

Section: Discussionmentioning

confidence: 99%

Intravenous Immunoglobulin Inhibits Liver Cancer Progression by Promoting p38MAPK-Associated Apoptosis

Lin

Liu

et al. 2022

Journal of Oncology

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Objective. The aim of this study is to explore the effect of intravenous immunoglobulin (IVIG) on the development of rat hepatocellular carcinoma and its possible molecular mechanism. Methods. Sixty adult male Sprague-Dawley (SD) rats were randomly divided into three groups: control, diethylnitrosamine(DEN) + normal saline(NS), and DEN + IVIG groups, with 20 rats in each group. The rats in the DEN + NS group and DEN + IVIG group were given DEN 0.2 g/kg intraperitoneal injection once on day 1 and then 0.05% DEN aqueous solution in drinking water to establish a rat liver cancer model. Immunoglobulin (IgG) was injected intraperitoneally into the DEN + IVIG group twice a week at the dose of 100 mg/kg, and saline was administered intraperitoneally into the control group at a 50 mg/kg dosage. The body weight of each group of rats was recorded twice a week. All treatments were maintained continuously for 12 weeks. After the intervention, the liver function indexes of rats were measured by a fully automated biochemical analysis instrument. The liver histopathology was observed by hematoxylin-eosin(HE) staining. Immunohistochemistry was used to detect c-myc protein expression, and Western blotting was used to determine p38MAPK and p-p38MAPK protein expressions, as well as apoptosis-related proteins such as Bcl-2, Bax, and cleaved caspase-3. Results. Compared with the rats in the DEN + NS group, rats in the DEN + IVIG group showed substantially higher body mass ( P < 0.05 ), higher survival rate ( P < 0.05 ), and lower liver function indexes ( P < 0.05 ). Few focal necrosis of cancer cells and few nuclear division were observed in the rats in the DEN + IVIG group. The rats in the DEN + NS group showed lamellar necrosis of cancer foci, destruction of normal liver lobular structure, and hepatocellular carcinoma cells. Immunohistochemical analysis results revealed that the expression of c-myc was reduced in the DEN + IVIG group ( P < 0.05 ), and Western blotting confirmed that the Bcl-2 expression was decreased ( P < 0.05 ), while Bax, p38 MAPK, p-p38 MAPK, and cleaved caspase-3 protein expressions were increased ( P < 0.05 ). Conclusion. IVIG prophylactic injection can delay tumor development and induce apoptosis in primary hepatocellular carcinoma in rats. The mechanism is connected to the activation of the p38MAPK signaling pathway by upregulating the level of cleaved caspase-3 and Bax proteins while downregulating the level of Bcl-2 and c-myc proteins.

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Section: Discussionmentioning

confidence: 99%

Intravenous Immunoglobulin Inhibits Liver Cancer Progression by Promoting p38MAPK-Associated Apoptosis

Lin

Liu

et al. 2022

Journal of Oncology

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The efficacy and potential mechanisms of pyrotinib in targeting EGFR and HER2 in advanced oral squamous cell carcinoma

Zhou,

Le,

Chen

et al. 2024

BMC Oral Health

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Background Human epidermal growth factor receptor 2 (HER2) plays an important role in the progression of multiple solid tumors and induces resistance to epidermal growth factor receptor (EGFR) target treatment. However, the expression status and the clinical significance of HER2 in oral squamous cell carcinoma (OSCC) is still controversial. Pyrotinib (PYR) is a promising novel EGFR/HER2 dual inhibitor, whose efficacy in OSCC has not been determined. Methods 57 locally advanced de novo OSCC patients were included in this study to investigate the relationship between the HER2 expression levels and the prognosis by the tissue microarray analysis (TMA). In vitro and in vivo experiments were performed to retrieve the efficacy of PYR in OSCC. The main downstream of HER2 was evaluated by western blotting in OSCC cell lines and xenograft tumors to explore the potential mechanism of PYR. Results This study revealed the primary tumor of OSCC had higher HER2 expression levels. Patients with HER2 overexpression had poor overall survival (P < 0.014) and poor disease free survival (P < 0.042). In vitro, PYR suppressed the proliferation, colony formation and migration of OSCC cells. It also promoted apoptosis of OSCC cells and induced cell cycle arrest. Furthermore, PYR was able to inhibit the occurrence and development of OSCC effectively in vivo. Western blotting revealed that PYR suppressed OSCC by inhibiting the phosphorylation of HER2, AKT and ERK. Conclusions This study exhibited the anti-OSCC effects of PYR in vitro and in vivo, and demonstrated PYR inhibited OSCC cells by inducing apoptosis via the HER2/ AKT and ERK pathway. The result of this study also indicated locally advanced OSCC patients might benefit from HER2 assay and EGFR/HER2 dual inhibit treatment.

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Challenges in the Development of NK-92 Cells as an Effective Universal Off-the-Shelf Cellular Therapeutic

Niu,

Wang,

Yan

et al. 2024

The Journal of Immunology

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The human-derived NK-92 cell–based CAR-NK therapy exhibits inconsistency with overall suboptimal efficacy and rapid in vivo clearance of CAR-NK92 cells in cancer patients. Analysis indicates that although pre-existing IgM in healthy individuals (n = 10) strongly recognizes both NK-92 and CAR-NK92 cells, IgG and IgE do not. However, only a subset of cancer patients (3/8) exhibit strong IgM recognition of these cells, with some (2/8) showing pre-existing IgG recognition. These results suggest a natural immunoreactivity between NK-92 and CAR-NK92 cells and pre-existing human Abs. Furthermore, the therapy’s immunogenicity is evidenced by enhanced IgG and IgM recognition postinfusion of CAR-NK92 cells. We also confirmed that healthy plasma’s cytotoxicity toward these cells is reduced by complement inhibitors, suggesting that Abs may facilitate the rapid clearance of CAR-NK92 cells through complement-dependent cytotoxicity. Given that NK-92 cells lack known receptors for IgG and IgM, identifying and modifying the recognition targets for these Abs on NK-92 and CAR-NK92 cells may improve clinical outcomes. Moreover, we discovered that the 72nd amino acid of the NKG2D receptor on NK-92 cells is alanine. Previous studies have demonstrated polymorphism at the 72nd amino acid of the NKG2D on human NK cells, with NKG2D72Thr exhibiting a superior activation effect on NK cells compared with NKG2D72Ala. We confirmed this conclusion also applies to NK-92 cells by in vitro cytotoxicity experiments. Therefore, reducing the immunoreactivity and immunogenicity of CAR-NK92 and directly switching NK-92 bearing NKG2D72Ala to NKG2D72Thr represent pressing challenges in realizing NK-92 cells as qualified universal off-the-shelf cellular therapeutics.

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Circulating Natural Autoantibodies to HER2-Derived Peptides Performed Antitumor Effects on Oral Squamous Cell Carcinoma

Cited by 3 publications

References 48 publications

Intravenous Immunoglobulin Inhibits Liver Cancer Progression by Promoting p38MAPK-Associated Apoptosis

Intravenous Immunoglobulin Inhibits Liver Cancer Progression by Promoting p38MAPK-Associated Apoptosis

The efficacy and potential mechanisms of pyrotinib in targeting EGFR and HER2 in advanced oral squamous cell carcinoma

Challenges in the Development of NK-92 Cells as an Effective Universal Off-the-Shelf Cellular Therapeutic

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