Tag: Id-1

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Cannabidiol Treatment Results in a Common Gene Expression Response Across Aggressive Cancer Cells from Various Origins

Abstract

Background: We previously reported that cannabidiol (CBD), a cannabinoid with a low toxicity profile, downregulated the expression of the prometastatic gene inhibitor of DNA binding 1 (ID1) in cancer cells, leading to inhibition of tumor progression in vivo. While CBD is broadly used, including in the self-medication of cancer patients, and CBD-based therapies are undergoing clinical evaluation for cancer treatment, its mechanisms of action are still poorly understood.

Methods: In this study, using microarray analysis and Western blot analysis for validation, we attempted to identify the full spectrum of genes regulated by CBD across various aggressive cancer cell lines, including the breast, brain, head and neck, and prostate.

Results: We confirmed that ID1 was a major target downregulated by CBD and also discovered that CBD inhibited FOXM1 (Forkhead box M1), a transcriptional activator involved in cell proliferation, while simultaneously upregulating GDF15 (growth differentiation factor 15), a cytokine associated with tissue differentiation.

Conclusion: Our results suggest that, by modulating expression of shared key cancer-driving genes, CBD could represent a promising nontoxic therapeutic for treating tumors of various origins.

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ID1 Is Critical for Tumorigenesis and Regulates Chemoresistance in Glioblastoma

Abstract

Glioblastoma is the most common primary brain tumor in adults. While the introduction of temozolomide chemotherapy has increased long-term survivorship, treatment failure and rapid tumor recurrence remains universal. The transcriptional regulatory protein, inhibitor of DNA-binding-1 (ID1), is a key regulator of cell phenotype in cancer. We show that CRISPR-mediated knockout of ID1 in glioblastoma cells, breast adenocarcinoma cells, and melanoma cells dramatically reduced tumor progression in all three cancer systems through transcriptional downregulation of EGF, which resulted in decreased EGFR phosphorylation. Moreover, ID1-positive cells were enriched by chemotherapy and drove tumor recurrence in glioblastoma. Addition of the neuroleptic drug pimozide to inhibit ID1 expression enhanced the cytotoxic effects of temozolomide therapy on glioma cells and significantly prolonged time to tumor recurrence. Conclusively, these data suggest ID1 could be a promising therapeutic target in patients with glioblastoma. SIGNIFICANCE: These findings show that the transcriptional regulator ID1 is critical for glioblastoma initiation and chemoresistance and that inhibition of ID1 enhances the effect of temozolomide, delays tumor recurrence, and prolongs survival.

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Expression of the inhibitor of DNA-binding (ID)-1 protein as an angiogenic mediator in tumour advancement of uterine cervical cancers

Abstract [CONDENSED]

…the 36-month survival rate of patients with high ID-1 was poor (60%), whereas that of the patients with low ID-1 was significantly higher (83%). ID-1 correlated with microvessel counts in uterine cervical cancers. ID-1 expression also correlated significantly with histoscore. Therefore, ID-1 might work on tumour advancement through angiogenic activity and is considered to be a candidate for a prognostic indicator in uterine cervical cancers.

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Overexpression of Id-1 protein is a marker in colorectal cancer progression

Abstract

The inhibitor of differentiation/DNA binding 1 (Id-1), a negative regulator of basic helix-loop-helix transcription factors, plays an important role in the regulation of cell proliferation and differentiation. We examined the Id-1 expression by immunohistochemistry in 9 adenomas, 79 primary colorectal adenocarcinomas matched with 40 adjacent normal mucosa specimens and its relationship with clinicopathological factors. The Id-1 expression was increased in the carcinoma compared to the adjacent normal mucosa either in the unmatched and matched samples or to the adenoma. There was no significant difference in the Id-1 expression between normal mucosa and adenoma. The Id-1 expression of carcinoma was increased from Dukes’ stages A to B, to C and to D. The cases with lymph node metastasis had a higher rate of a stronger Id-1 expression than those without lymph node metastasis. In conclusion, Id-1 overexpression plays an important role in colorectal cancer progression.

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Level of Id-1 Protein Expression Correlates with Poor Differentiation, Enhanced Malignant Potential, and More Aggressive Clinical Behavior of Epithelial Ovarian Tumors

Abstract [condensed]

Strong or moderate expression of Id-1 was a strong predictor for shorter overall survival. The level of Id-1 protein expression correlates with the malignant potential of ovarian tumors. In cancer samples, stronger Id-1 expression is associated with poor differentiation and more aggressive behavior of tumor cells, resulting in poor clinical outcome. Consequently, Id-1 inhibition in the future might be of benefit for patients with ovarian cancer.

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Overexpression of Id-1 Protein Is a Marker for Unfavorable Prognosis in Early-Stage Cervical Cancer

Abstract [condensed]

We investigated the prognostic influence of Id-1 expression in 89 patients with cervical cancer. patients with strong or moderate expression of Id-1 had a significant shorter overall survival time and disease-free survival time compared with those with low or absent Id-1 expression. Id-1 expression is an independent prognostic marker in early-stage cervical cancer.

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