EGFR High Expression, but not KRAS Status, Predicts Sensitivity of Pancreatic Cancer Cells to Nimotuzumab Treatment In Vivo

Zhou, Chenfei; Zhu, Liangjun; Ji, Jun; Ding, Fangmi; Wang, Chao; Cai, Qing; Yu, Yingyan; Zhu, Zhenggang; Zhang, Jun

doi:10.2174/1568009616666161013101657

Cited by 12 publications

(11 citation statements)

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“…Nimotuzumab has previously been shown by immunohistochemistry to decrease IL-6 in mice xenografted with pancreatic cell lines overexpressing EGFR. This result was confirmed by western blot and real-time PCR [ 36 ].…”

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confidence: 59%

Nimotuzumab for COVID-19: Case Series

Abdo-Cuza¹,

Ávila²,

Martínez³

et al. 2021

Immunotherapy

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Background: In COVID-19, EGFR production is upregulated in the alveolar epithelial cells. EGFR overexpression further activates STAT-3 and increases lung pathology. The EGFR pathway is also one of the major nodes in pulmonary fibrosis. Methods: Nimotuzumab, a humanized anti-EGFR antibody, was used to treat three patients with severe or moderate COVID-19. The antibody was administered in combination with other drugs included in the national COVID-19 protocol. Results: Nimotuzumab was well tolerated. IL-6 decreased from the first antibody infusion. Clinical symptoms significantly improved after nimotuzumab administration, and the CT scans at discharge showed major resolution of the lung lesions and no signs of fibrosis. Conclusion: Safe anti-EGFR antibodies like nimotuzumab may modulate COVID-19-associated hyperinflammation and prevent fibrosis. Clinical Trial Registration: RPCEC00000369 (RPCEC rpcec.sld.cu).

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confidence: 59%

Nimotuzumab for COVID-19: Case Series

Abdo-Cuza¹,

Ávila²,

Martínez³

et al. 2021

Immunotherapy

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“…16 Moreover, antitumor efficacy of Nimo was not impacted by KRAS status in pancreatic cancer cells in vivo. 18 Furthermore, the addition of Nimo to chemotherapy/radiotherapy or chemoradiotherapy was well-tolerant. A phase I dose escalation study of Nimo plus CCRT in LA-ESCC indicated Nimo of 400 mg/week delivered with CCRT was well-tolerant and no dose-limiting toxicities were observed.…”

Section: Discussionmentioning

confidence: 99%

“…15 The differences in the affinity on EGF and pathways and other possible mechanisms make it possible for Nimo to be more promising than C225 in triple therapy of EC. [16][17][18] In view of the excellent performance of C225 in head and neck squamous cell carcinoma, the combination of anti-EGFR and chemoradiation in ESCC should not be easily abandoned. Hence, it is urgently needed to evaluate the efficacy of Nimo in ESCC compared with other anti-EGFR drugs.…”

Section: Introductionmentioning

confidence: 99%

Slight advantages of nimotuzumab versus cetuximab plus concurrent chemoradiotherapy in locally advanced esophageal squamous cell carcinoma

Wang

Yan

Liu

et al. 2019

Cancer Biology & Therapy

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This study aimed to compare the efficacy of nimotuzumab (Nimo) versus cetuximab (C225) plus concurrent chemoradiotherapy (CCRT) in locally advanced esophageal squamous cell carcinoma (LA-ESCC). A total of 95 patients with LA-ESCC were retrospectively reviewed, including 65 in Nimo and 30 in C225. The results showed that the ORR in Nimo (61.0%; CR 22.0%, 13/59; PR 39.0% 23/59) was slightly higher than that in C225 (43.5%; CR 8.7%, 2/23; PR 34.8%, 8/23) but without significant difference (p = 0.81). The DCR was 79.7% vs. 73.9% in C225, favoring Nimo plus CCRT (p = 0.04). The median PFS in Nimo was significantly longer than that in C225 (19.6 months vs. 13.0 months, p = 0.02). The median OS of the whole cohort, the Nimo group and the C225 group were 21.3, 24.5, and 20.9 months, respectively. The rates of OS at 1-, 3-year in Nimo were 77.7% and 33.5%, compared to 73.3% and 20.0% in C225 (HR = 1.17, p = 0.23). Grade 3 or worse hematological toxicity and non-hematological toxicity (radiation esophagitis) in Nimo were similar with that in C225 (21.5% vs. 26.7%, p = 0.91; 26.1% vs. 26.7%, p = 0.56). No grade ≥3 radiation pneumonitis occurred neither Nimo group nor C225 group. Nimo plus CCRT improved DCR and PFS of patients with LA-ESCC and had a tendency of prolonged survival compared to C225 plus CCRT. Our results suggest that the combination of Nimo and CCRT may be a reasonable option in this population.

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“…EGF binds to EGFR and causes EGFR-specific tyrosine residue phosphorylation, thereby leading to activation of signal transduction pathways, including MAPK/ERK and PI3K/Akt pathways [ 6 – 8 ]. EGFR is highly expressed in a variety of human malignancies [ 9 , 10 ]. In recent years, important advances have been made in the study of EGFR, including indications that EGFR-mediated signal transduction is closely linked to the occurrence, development, and prognosis of malignant tumors [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Cyclic Guanosine Monophosphate (cGMP)-Dependent Protein Kinase II Blocks Epidermal Growth Factor (EGF)/Epidermal Growth Factor Receptor (EGFR)-Induced Biological Effects on Osteosarcoma Cells

Hua

Jiang

et al. 2018

Med Sci Monit

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BackgroundThe present work was performed to detect the potential inhibitory effect of cyclic guanosine monophosphate (cGMP)-dependent protein kinase II (PKG II) on epidermal growth factor (EGF) receptor-induced biological activity and related signal cascades in osteosarcoma cells.Material/MethodsWe transfected the osteosarcoma MG-63 cell line with an adenoviral vector encoding PKG II cDNA (Ad-PKGII) and incubated the transfected cells with 250 μM 8-pCPT-cGMP to activate the PKG II. We stimulated the MG-63 cells with100 ng/ml EGF, and then detected their proliferation using a CCK-8 assay. Transwell assay was used to examine MG-63 cell migration; and Western blot analysis was used to detect expression of matrix metalloproteinase 9 (MMP-9) and activation of ERK and Akt.ResultsStimulating cells by 100 ng/ml EGF promoted MG-63 cell proliferation and migration, ERK and Akt phosphorylation, and MMP-9 expression. These effects of EGF were inhibited in MG-63 cells infected with Ad-PKGII and incubated with 8-pCPT-cGMP.ConclusionsOur results demonstrate that Ad-PKGII infection significantly inhibited EGF-induced proliferation and migration, as well as the associated-signal cascades; which indicates that PKG II might be a potential anti-cancer factor.

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EGFR High Expression, but not KRAS Status, Predicts Sensitivity of Pancreatic Cancer Cells to Nimotuzumab Treatment In Vivo

Abstract: Pancreatic cancer cells with EGFR high expression were more sensitive to nimotuzumab in vivo. KRAS status had no impact on anti-tumor efficacy of nimotuzumab in pancreatic cancer cells.

Cited by 12 publications

References 0 publications

Nimotuzumab for COVID-19: Case Series

Nimotuzumab for COVID-19: Case Series

Slight advantages of nimotuzumab versus cetuximab plus concurrent chemoradiotherapy in locally advanced esophageal squamous cell carcinoma

Cyclic Guanosine Monophosphate (cGMP)-Dependent Protein Kinase II Blocks Epidermal Growth Factor (EGF)/Epidermal Growth Factor Receptor (EGFR)-Induced Biological Effects on Osteosarcoma Cells

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