Characterizing Cell Stress and GRP78 in Glioma to Enhance Tumor Treatment

Abstract

Glioblastoma (GBM) is the most common primary brain tumor, carrying a very poor prognosis, with median overall survival at about 12 to 15 months despite surgical resection, chemotherapy with temozolomide (TMZ), and radiation therapy. GBM recurs in the vast majority of patients, with recurrent tumors commonly displaying increase in resistance to standard of care chemotherapy, TMZ, as well as radiotherapy. One of the most commonly cited mechanisms of chemotherapeutic and radio-resistance occurs via the glucose-regulated protein 78 (GRP78), a well-studied mediator of the unfolded protein response (UPR), that has also demonstrated potential as a biomarker in GBM. Overexpression of GRP78 has been directly correlated with malignant tumor characteristics, including higher tumor grade, cellular proliferation, migration, invasion, poorer responses to TMZ and radiation therapy, and poorer patient outcomes. GRP78 expression is also higher in GBM tumor cells upon recurrence. Meanwhile, knockdown or suppression of GRP78 has been shown to sensitize cells to TMZ and radiation therapy. In light of these findings, various novel developing therapies are targeting GRP78 as monotherapies, combination therapies that enhance the effects of TMZ and radiation therapy, and as treatment delivery modalities. In this review, we delineate the mechanisms by which GRP78 has been noted to specifically modulate glioblastoma behavior and discuss current developing therapies involving GRP78 in GBM. While further research is necessary to translate these developing therapies into clinical settings, GRP78-based therapies hold promise in improving current standard-of-care GBM therapy and may ultimately lead to improved patient outcomes.

The role of GRP78 in oxidative stress induced by tunicamycin in trabecular meshwork cells

“…When the ER stress response is too strong and too long, the apoptotic pathway can be initiated, which leads to abnormal cell function and finally leads to cell death. When the ER stress response capacity is low, the effective cell protection mechanism is reduced, and the sensitivity of cells to injurious stimuli is increased, which leads to or accelerates cell death (Liu et al, 2020). In our study, it was found that tunicamycin could induce ER stress in trabecular meshwork cells and increased the cell apoptosis rate.…”

The Clinical Value of High-Quality Nursing in Concurrent Radiotherapy and Chemotherapy after Glioma Surgery and Its Influence on the Stress Indicators Cor, ACTH, and CRP

“…Both surgical stress and radiotherapy and chemotherapy stress can cause the patient's stress response, causing physiological and psychological abnormalities in the patient, resulting in neurological disorders; the adrenal medulla secretes catecholamines and abnormal sympathetic activity, which in turn leads to endocrine and immune system disorders [ 20 , 21 ]. The body's stress response is physiologically mainly through the activation of the hypothalamus-pituitary-adrenal cortex endocrine axis and the sympathetic-adrenal medulla endocrine axis.…”

“…e results show that high-quality nursing intervention can significantly improve the satisfaction of patients with glioma during concurrent radiotherapy and chemotherapy and improve the compliance of patients with treatment, which is conducive to the establishment of a good doctorpatient relationship and promotes the postoperative recovery of patients. Both surgical stress and radiotherapy and chemotherapy stress can cause the patient's stress response, causing physiological and psychological abnormalities in the patient, resulting in neurological disorders; the adrenal medulla secretes catecholamines and abnormal sympathetic activity, which in turn leads to endocrine and immune system disorders [20,21]. e body's stress response is physiologically mainly through the activation of the hypothalamus-pituitaryadrenal cortex endocrine axis and the sympathetic-adrenal medulla endocrine axis.…”

In vivo CRISPR screening for novel noncoding RNA functional targets in glioblastoma models

“…However, it is notable that there is a modest increase in mass (19 mg vs. 11.1 mg, p = 0.02) and volume (17.4 cc vs. 9.0 cc, p = 0.01) among sgRNA‐transduced cells versus control. A component of this increased tumor size among transduced cells may be related to the common practice of implantation of tumor soon after puromycin selection, as puromycin has been noted to induce cell stress changes associated with increased GB growth (Liu et al., 2020; Oguma et al., 2009). Ultimately, however, we must stress that CRISPRi screen relies on hundreds of transduced nontargeting sgRNA controls to function as the experimental controls for the candidate lncRNA sgRNAs.…”