Expression of toll-like receptors and inflammatory mediators in primary human glioma cells (low- and high-grade) compared to primary cells from epileptic human brain.

Objectives: Toll-like receptors (TLRs) have been implicated in the pathogenesis of glioma as principal regulators of inflammation and innate immune function. Considering the heterogeneous nature of gliomas, ranging from low to high grade with different therapeutic responses, investigating the differences in the levels of TLR2 and TLR4 and associated inflammatory markers in these distinct groups is of great clinical significance.

Materials And Methods: In this study, we investigated changes in the protein expression levels of TLR2 and TLR4, along with key inflammatory mediators, including nuclear factor kappa B (NF-κB) as a downstream signaling molecule, and tumor necrosis factor-alpha (TNF-α), a target of NF-κB activation, by using western blotting.

Regulatory role of circular RNAs in the development of therapeutic resistance in the glioma: A double-edged sword.

Gliomas are the most common lethal tumors of the brain associated with a poor prognosis and increased resistance to chemo-radiotherapy. Circular RNAs (circRNAs), newly identified noncoding RNAs, have appeared as critical regulators of therapeutic resistance among multiple cancers and gliomas. Since circRNAs are aberrantly expressed in glioma and may act as promoters or inhibitors of therapeutic resistance, we categorized alterations of these specific RNAs expression in therapy resistant-glioma in three different classes, including chemoresistance, radioresistance, and glioma stem cell (GSC)-regulation.

Enhancing 5-ALA-PDT efficacy against resistant tumor cells: Strategies and advances.

As a precursor of protoporphyrin IX (PpIX), an endogenous pro-apoptotic and fluorescent molecule, 5-Aminolevulinic acid (5-ALA) has gained substantial attention for its potential in fluorescence-guided surgery as well as photodynamic therapy (PDT). Moreover, 5-ALA-PDT has been suggested as a promising chemo-radio sensitization therapy for various cancers. However, insufficient 5-ALA-induced PpIX fluorescence and the induction of multiple resistance mechanisms may hinder the 5-ALA-PDT clinical outcome.

The In Vitro Pro-inflammatory Functions of the SP/NK1R System in Prostate Cancer: a Focus on Nuclear Factor-Kappa B (NF-κB) and Its Pro-inflammatory Target Genes.

Prostate cancer is one of the main global health threats for men which is in close association with chronic inflammation. Neuropeptide substance P (SP), acting through neurokinin receptor (NK-1R), induces various pro-inflammatory responses which are strongly involved in the pathogenesis of several diseases as well as cancer. Therefore, we aimed to investigate the pro-inflammatory functions of the SP/NK1R complex in prostate cancer and the therapeutic effects of its inhibition by NK-1R antagonist, aprepitant, in vitro.

The in vitro anti-cancer synergy of neurokinin-1 receptor antagonist, aprepitant, and 5-aminolevulinic acid in glioblastoma.

Glioblastoma multiforme (GBM) is the most malignant type of cerebral neoplasm in adults with a poor prognosis. Currently, combination therapy with different anti-cancer agents is at the forefront of GBM research. Hence, this study aims to evaluate the potential anti-cancer synergy of a clinically approved neurokinin-1 receptor antagonist, aprepitant, and 5-aminolevulinic acid (5-ALA), a prodrug that elicits fluorescent porphyrins in gliomas on U-87 human GBM cells.

The neuropeptide substance P/neurokinin-1 receptor system and diabetes: From mechanism to therapy.

Diabetes is a significant public health issue known as the world's fastest-growing disease condition. It is characterized by persistent hyperglycemia and subsequent chronic complications leading to organ dysfunction and, ultimately, the failure of target organs. Substance P (SP) is an undecapeptide that belongs to the family of tachykinin (TK) peptides.

The Effect of Blocking Neurokinin-1 Receptor by Aprepitant on the Inflammatory and Apoptosis Pathways in Human Ovarian Cancer Cells.

Ovarian cancer is the seventh most common cancer globally, and the second most common cancer among women with significant mortality. Toward this end, it is shown that substance P (SP) is involved in tumor initiation and progression through the neurokinin-1 receptor (NK1R). However, the exact molecular mechanism of the SP/NK1R system in ovarian cancer is not yet fully clarified.

The Potential In Vitro Inhibitory Effects of Neurokinin-1 Receptor (NK-1R) Antagonist, Aprepitant, in Osteosarcoma Cell Migration and Metastasis.

Background: Osteosarcoma, the most frequent osteogenic malignancy, has become a serious public health challenge due to its high morbidity rates and metastatic potential. Recently, the neurokinin-1 receptor (NK-1R) is proved to be a promising target in cancer therapy. This study is aimed at determining the effect of aprepitant, a safe and Food and Drug Administration (FDA) approved NK-1R antagonist, on osteosarcoma cell migration and metastasis, and to explore its underlying mechanism of action.

The redox modulatory effects of SP/NK1R system: Implications for oxidative stress-associated disorders.

Oxidative stress which refers to redox imbalance with increased generation of reactive oxygen species (ROS) has been associated with the pathophysiology of diverse disease conditions. Recently, a close, yet not fully understood, relation between oxidative stress and neuropeptides, in particular, substance P (SP), has been reported in certain conditions. SP has been shown to affect the cellular redox environment through activation of neurokinin-1receptor (NK1R).

Inhibition of angiotensin pathway via valsartan reduces tumor growth in models of colorectal cancer.

Background: Overexpression of the angiotensin-II receptor and renin-angiotensin system (RAS) has been reported in several malignancies, including colorectal-cancer (CRC), indicating its potential value as a therapeutic target. Here we explored the impact of targeting the RAS using an angiotensin II receptor blocker, valsartan, alone and its combination with Fluorouracil (5-FU) in in vitro and in vivo models of CRC.

Methods: Anti-proliferative activity of valsartan was evaluated in 2-/3-dimensional in vitro and in vivo CRC mouse models.

SP/NK1R system regulates carcinogenesis in prostate cancer: Shedding light on the antitumoral function of aprepitant.

Aims: Prostate cancer continues to be one of the main global health issues in men. Neuropeptide substance P (SP) acting via neurokinin-1receptor (NK1R) promotes tumorigenicity in many human malignant tumors. However, its pro-tumorigenic functions and the therapeutic effects of its inhibition in prostate cancer remain unclear.

The SP/NK1R System-Mediated ROS Generation in GBM Cells through Inhibiting Glutaredoxin Protein.

Altered redox balance is among the main contributing factors developing glioblastoma multiforme (GBM), a highly aggressive grade IV brain tumor. Neuropeptide substance P (SP) plays a key role in modifying the cellular redox environment by activating the neurokinin-1 receptor (NK1R). In this study, we aimed to investigate the redox-modulating properties of both SP and a commercially available NK1R antagonist, aprepitant in GBM cells.

Potential in vitro therapeutic effects of targeting SP/NK1R system in cervical cancer.

Background: Cervical cancer, an aggressive gynecological cancer, seriously threatens women's health worldwide. It is recently reported that neuropeptide substance P (SP) regulates many tumor-associated processes through neurokinin-1 receptor (NK1R). Therefore, we used cervical cancer cell line (HeLa) to investigate the functional relevance of the SP/NK1R system in cervical cancer pathogenesis.

Pathogenic role of the SP/ NK1R system in GBM cells through inhibiting the thioredoxin system.

Objectives: Glioblastoma multiforme (GBM), a highly aggressive Grade IV brain tumor, is a significant public health issue due to its poor prognosis and incurability. Neuropeptide substance P (SP) plays a critical role in GBM tumor growth and development via activation of neurokinin-1receptor (NK1R). Moreover, SP is a pro-oxidant factor contributing to oxidative stress in various cell types.

MicroRNA Regulation of Androgen Receptor in Castration-Resistant Prostate Cancer: Premises, Promises, and Potentials.

Prostate cancer (PCa) is the second most prevalent cancer and the fifth leading cause of cancer-related deaths among men. Androgen deprivation therapy (ADT) is the most frequently used therapeutic strategy in PCa; however, the development of resistance to ADT, known as castration- resistant prostate cancer (CRPC), continues to be a major obstacle against the successful treatment of PCa. The abnormal activation of the androgen receptor (AR) signaling pathway has been found as one of the main contributing factors to the development of resistance in CRPC.

New insight into the role of substance P/neurokinin-1 receptor system in breast cancer progression and its crosstalk with microRNAs.

The neuropeptide substance P (SP) triggers a variety of tumor-promoting signaling pathways through the activation of neurokinin-1receptor (NK1R), a class of neurokinin G protein-coupled receptors superfamily. Recent researches in our and other laboratories have shown the overexpression of both SP and NK1R in breast cancer (BC) patients. SP/NK1R signaling is strongly implicated in the pathogenesis of BC through affecting cell proliferation, migration, metastasis, angiogenesis, and resistance.

Diagnostic, Prognostic, and Therapeutic Potencies of Circulating miRNAs in Acute Myocardial Infarction.

Acute myocardial infarction (AMI), or heart attack, is a major public health problem, responsible for 3 to 4 million deaths each year. Despite great improvements in diagnostic and therapeutic strategies, it remains one of the most lethal types of heart disease. Therefore, the identification of molecular mechanisms involved in AMI pathogenesis might help us to develop new therapeutic and diagnostic approaches.

MicroRNA-mediated redox regulation modulates therapy resistance in cancer cells: clinical perspectives.

Background: Chemotherapy and radiation therapy are the most common types of cancer therapy. The development of chemo/radio-resistance remains, however, a major obstacle. Altered redox balances are among of the main factors mediating therapy resistance.

Adherence to a healthy dietary pattern is associated with less severe depressive symptoms among adolescent girls.

There is growing interest on the impact of diet on depressive disorders. However, there are limited data on the association between dietary patterns and depression symptoms among Iranian adolescents. The aim of this study was to evaluate the association between dietary patterns and depression score among Iranian adolescent girls.

Oxidative stress in cervical cancer pathogenesis and resistance to therapy.

Cervical cancer (CC) is one of the most common cancers among females, and it is most notable in developing countries. The exact etiology of CC is poorly understood; but, smoking, oral contraceptives, immunosuppression, and infection with human papillomavirus (HPV) may increase the risk of CC. There is also an association between CC and oxidative stress.

Therapeutic potency of oncolytic virotherapy in breast cancer targeting, current status and perspective.

Breast cancer is the most common cause of cancer death in women and presents a serious therapeutic challenge worldwide. Traditional treatments are less successful at targeting cancer tumors, leading to recurrent treatment-resistant secondary malignancies. Oncolytic virotherapy (OV) is a novel anticancer strategy with therapeutic implications at targeting cancer cells by using mechanisms that differ from conventional therapies.

Role of adenosine signaling in the pathogenesis of head and neck cancer.

The concentrations of adenosine may increase under ischemic conditions in the tumor microenvironment, and then it enters the systemic circulation. Adenosine controls cancer progression and responses to therapy by regulating angiogenesis, cell survival, apoptosis, cell proliferation, and metastases in tumors. Hence, adenosine metabolism, adenosine-generating enzymes, and adenosine signaling are potentially novel therapeutic targets in a wide range of pathological conditions, including cerebral and cardiac ischemic diseases, inflammatory disorders, immunomodulatory disorders, and, of special interest in this review, cancer.

Targeting the Akt/PI3K Signaling Pathway as a Potential Therapeutic Strategy for the Treatment of Pancreatic Cancer.

The phosphoinositide 3 kinase AKT mammalian target of rapamycin (PI3K-AKTmTOR) signaling pathway is an important in the aetiology of pancreatic cancer (PC) and is frequently activated in PC. It is then associated with a poorer prognosis. Aberrant activation of this pathway is involved in cell metabolism and survival, cell cycle progression, regulation of apoptosis, protein synthesis, and genomic instability.

Interferon-Mediated Tumor Resistance to Oncolytic Virotherapy.

Interferons (INFs) elicit antiviral responses in tumor cells upon binding to cell surface receptors. Oncolytic virotherapy (OV) is an effective antitumor therapeutic approach which in combination with standard radiotherapy or chemotherapy regimens potentiates treatment responses in cancer patients. However, oncolytic viruses are susceptible to the IFN-induced antiviral state in the tumor microenvironment.