Research progress of opioid growth factor in immune-related diseases and cancer diseases

Huang, Hai; Liu, Bing; Qu, Na; Zhang, Shuling; Bai, Xueli; Handley, Mike; Shan, Fengping

doi:10.1016/j.intimp.2021.107713

Cited by 7 publications

(5 citation statements)

References 132 publications

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“…The binding of OGF and OGFR leads to translocation in the nucleus and plays a role in regulating cell growth and immune function. 43 Several preclinical and clinical studies have shown that modulating the natural OGF-OGFR regulatory network represents a new non-toxic and highly effective approach to tumor therapy. 43 , 44 The present study found a high expression of OGFR in several tumor tissues, which provides a rationale for the use of OGF as part of adjuvant therapy for cancer.…”

Section: Discussionmentioning

confidence: 99%

“… 43 Several preclinical and clinical studies have shown that modulating the natural OGF-OGFR regulatory network represents a new non-toxic and highly effective approach to tumor therapy. 43 , 44 The present study found a high expression of OGFR in several tumor tissues, which provides a rationale for the use of OGF as part of adjuvant therapy for cancer. Several factors contribute to gene expression, encompassing miRNA alterations and DNA methylation.…”

Section: Discussionmentioning

confidence: 99%

“…The binding of OGF and OGFR leads to translocation in the nucleus and plays a role in regulating cell growth and immune function. 43…”

Section: Discussionmentioning

confidence: 99%

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Pan-Cancer Analysis and Validation of Opioid-Related Receptors Reveals the Immunotherapeutic Value of Toll-Like Receptor 4

Wu,

Chen,

Huang

et al. 2023

IJGM

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Introduction The relationship between the expression of opioid-associated receptors and cancer outcomes is complex and varies among studies. Methods This study focused on six opioid-related receptors (OPRM1, OPRD1, OPRK1, OPRL1, OGFR, and TLR4) and their impact on cancer patient survival. Bioinformatics analysis was conducted on 33 cancer types from The Cancer Genome Atlas database to examine their expression, clinical correlations, mechanisms in the tumor microenvironment, and potential for immunotherapy. Due to significantly lower expression of OPRM1, OPRD1, and OPRK1 compared to OGFR and TLR4, the analysis concentrated on the latter two genes. Results OGFR was highly expressed in 16 tumor types, while TLR4 showed low expression in 13. Validation from external samples, the Gene Expression Omnibus, and the Human Protein Atlas supported these findings. The diagnostic value of these two genes was demonstrated using the Genotype-Tissue Expression database. Univariate Cox regression models and Kaplan-Meier curves confirmed OGFR’s impact on prognosis in a cancer type-specific manner, while high TLR4 expression was associated with a favorable prognosis. Analysis of the tumor microenvironment using a deconvolution algorithm linked OGFR to CD8+ T cells and TLR4 to macrophages. Single-cell datasets further validated this correlation. In 25 immune checkpoint blockade treatment cohorts, TLR4 expression showed promise as an immunotherapy efficacy predictor in non-small cell lung cancer, urothelial carcinoma, and melanoma. Conclusion In a pan-cancer analysis of 33 tissues, OGFR was consistently highly expressed, while TLR4 had low expression. Both genes have diagnostic and prognostic significance and are linked to immune cells in the tumor microenvironment. TLR4 has potential as an immunotherapeutic response marker.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Pan-Cancer Analysis and Validation of Opioid-Related Receptors Reveals the Immunotherapeutic Value of Toll-Like Receptor 4

Wu,

Chen,

Huang

et al. 2023

IJGM

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“…Morphine-induced activation of the µ-opioid receptor led to an increase in the expression of the epidermal growth factor receptor (EGFR), which caused an increase in proliferation in vitro of human non-small cell lung cancer (NSCLC) cell lines through phosphorylation of MAPK, ERK, and protein kinase B, which are responsible for triggering the synthesis of proteins involved in the proliferation, migration, and epithelial-mesenchymal transition of cancer cells [ 10 ]. Numerous literature data provide evidence of µ receptor overexpression in cancers, such as negative breast cancer [ 2 ], pancreatic cancer [ 11 ], colon cancer [ 12 ], esophageal squamous cell carcinoma [ 13 , 14 ] and laryngeal cancer [ 15 ], stomach cancer [ 16 ], hepatocellular carcinoma [ 17 ], prostate cancer, and lung cancer [ 18 ]. In addition to the increased expression of µ-opioid receptors in numerous types of cancers, an increase in the expression of another target point, namely the ζ-opioid receptor, has also been observed in these cells, whose signaling is closely related to the proliferation and survival of cells that have undergone carcinogenesis [ 19 ].…”

Section: The µ Receptor and Cancermentioning

confidence: 99%

Low-Dose Naltrexone as an Adjuvant in Combined Anticancer Therapy

Ciwun,

Tankiewicz-Kwedlo,

Pawlak

2024

Cancers

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Naltrexone (NTX) is a non-selective antagonist of opioid receptors, primarily used in the therapy of opioid and alcohol dependence. Low-dose naltrexone (LDN) exhibits antagonistic action against the opioid growth factor receptor (OGFr), whose signaling is associated with the survival, proliferation, and invasion of cancer cells. The mechanism of action of LDN depends on the dose and duration of the OGFr blockade, leading to a compensatory increase in the synthesis of the opioid growth factor (OGF), which has an inhibitory effect on carcinogenesis. Numerous studies on in vitro and in vivo models provide evidence of LDN’s positive impact on inhibiting the OGF–OGFr axis in cancers. LDN’s unique mechanism of action on cancer cells, lack of direct cytotoxic effect, and immunomodulating action form the basis for its use as an adjuvant in chemotherapy and immunotherapy of cancerous lesions.

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“…Lastly, we included the OGFr in our search for evidence of ORs expression in cancer even though it is not a classical opioid receptor. The nuclear membrane receptor OGFr, which responds to the endogenous opioid peptides OGF or met-enkephalin, is a known negative regulator of cell proliferation, which controls, amongst other processes, tumour growth and angiogenesis ( 83 ). OGFr responds to naltrexone resulting in suppression of cell proliferation, and upregulation of the OGFr ( 84 ).…”

Section: Evidence That Opioids May Influence Cancer Outcomes Via Other Receptorsmentioning

confidence: 99%

Opioid Receptor-Mediated and Non-Opioid Receptor-Mediated Roles of Opioids in Tumour Growth and Metastasis

et al. 2021

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Opioids are administered to cancer patients in the period surrounding tumour excision, and in the management of cancer-associated pain. The effects of opioids on tumour growth and metastasis, and their consequences on disease outcome, continue to be the object of polarised, discrepant literature. It is becoming clear that opioids contribute a range of direct and indirect effects to the biology of solid tumours, to the anticancer immune response, inflammation, angiogenesis and importantly, to the tumour-promoting effects of pain. A common misconception in the literature is that the effect of opioid agonists equates the effect of the mu-opioid receptor, the major target of the analgesic effect of this class of drugs. We review the evidence on opioid receptor expression in cancer, opioid receptor polymorphisms and cancer outcome, the effect of opioid antagonists, especially the peripheral antagonist methylnaltrexone, and lastly, the evidence available of a role for opioids through non-opioid receptor mediated actions.

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Research progress of opioid growth factor in immune-related diseases and cancer diseases

Cited by 7 publications

References 132 publications

Pan-Cancer Analysis and Validation of Opioid-Related Receptors Reveals the Immunotherapeutic Value of Toll-Like Receptor 4

Pan-Cancer Analysis and Validation of Opioid-Related Receptors Reveals the Immunotherapeutic Value of Toll-Like Receptor 4

Low-Dose Naltrexone as an Adjuvant in Combined Anticancer Therapy

Opioid Receptor-Mediated and Non-Opioid Receptor-Mediated Roles of Opioids in Tumour Growth and Metastasis

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