Drug repositioning in castration-resistant prostate cancer using systems biology and computational drug design techniques.

Background And Objective: Castration-resistant prostate cancer (CRPC) is caused by resistance to androgen deprivation treatment and leads to the death of patients and there is almost no chance of survival. Therefore, finding a cure to overcome CRPC is challenging and important, but discovering a new drug is very time-consuming and expensive. To overcome these problems, we used Drug repositioning (drug repurposing) strategy in this study.

CRISPR/Cas9 system: a novel approach to overcome chemotherapy and radiotherapy resistance in cancer.

Cancer presents a global health challenge with rising incidence and mortality. Despite treatment advances in cancer therapy, radiotherapy and chemotherapy remained the most common treatments for all types of cancers. However, resistance phenotype in cancer cells leads to unsatisfactory results in the efficiency of therapeutic strategies.

Inhibition of melanoma cell migration and invasion by natural coumarin auraptene through regulating EMT markers and reducing MMP-2 and MMP-9 activity.

Melanoma, the most invasive form of skin cancer, shows a rising incidence trend in industrial countries. Since the main reason for the failure of current therapeutic approaches against melanoma is metastasis, there is a great interest in introducing effective natural agents to combat melanoma cell migration and invasion. Auraptene (AUR) is the most abundant coumarin derivative in nature with valuable pharmaceutical effects.

Galbanic acid suppresses melanoma cell migration and invasion by reducing MMP activity and downregulating N-cadherin and fibronectin.

High mortality rate of melanoma is due to the metastasis of malignant cells. Galbanic acid (GBA) is a natural sesquiterpene coumarin with valuable pharmaceutical activities. Our study aimed to investigate whether GBA can affect the migration, invasion, and adhesion of melanoma cells.

MiR-548c-3p through suppressing and increases the sensitivity of colorectal cancer cells to 5-fluorouracil.

Background: Colorectal cancer, is one of most prevalent the cancer in the world. 5-Fluorouracil is a standard chemotherapeutic drug while the acquisition of resistance to 5-Fluorouracil is one of the problems during treatment. In this study, we aimed to find the miRNAs that modulate the expression of and as resistance-inducing genes in the resistant cell lines to 5-Fluorouracil.

Improving the efficacy of peptide vaccines in cancer immunotherapy.

Peptide vaccines have shown great potential in cancer immunotherapy by targeting tumor antigens and activating the patient's immune system to mount a specific response against cancer cells. However, the efficacy of peptide vaccines in inducing a sustained immune response and achieving clinical benefit remains a major challenge. In this review, we discuss the current status of peptide vaccines in cancer immunotherapy and strategies to improve their efficacy.

Nanoliposomal VEGF-R2 peptide vaccine acts as an effective therapeutic vaccine in a murine B16F10 model of melanoma.

Background: The vascular endothelial growth factor receptor-2 (VEGFR-2) plays an important role in melanoma development and progression. Peptide vaccines have shown great potential in cancer immunotherapy by targeting VEGFR-2 as a tumor-associated antigen and boosting the immune response against both tumor cells and tumor endothelial cells. Despite this, the low efficiency of peptide vaccines has resulted in moderate therapeutic results in the majority of studies.

Tamoxifen resistance induction results in the upregulation of ABCG2 expression and mitoxantrone resistance in MCF-7 breast cancer cells.

Cancer endocrine therapy can promote evolutionary dynamics and lead to changes in the gene expression profile of tumor cells. We aimed to assess the effect of tamoxifen (TAM)-resistance induction on ABCG2 pump mRNA, protein, and activity in ER + MCF-7 breast cancer cells. We also evaluated if the resistance to TAM leads to the cross-resistance toward mitoxantrone (MX), a well-known substrate of the ABCG2 pump.

7-Geranyloxcycoumarin enhances radio sensitivity in human prostate cancer cells.

Background: Prostate cancer is the second most prevalent and the fifth deadliest cancer among men worldwide. To improve radiotherapy outcome, we investigated the effects of 7-geranyloxycoumarin, also known as auraptene (AUR), on radiation response of prostate cancer cells.

Methods And Results: PC3 cells were pretreated with 20 and 40 µM AUR for 24, 48 and 72 h, followed by X-ray exposure (2, 4 and 6 Gy).

Expression analysis elucidates the roles of Nicastrin, Notch4, and Hes1 in prognosis and endocrine-therapy resistance in ER-positive breast cancer patients.

Background And Purpose: Although some proposed mechanisms responsible for tamoxifen resistance have already been present, further study is needed to determine the mechanisms underlying tamoxifen resistance more clearly. The critical role of Notch signaling has been described in promoting resistance in therapeutics, but there is little information about its role in tamoxifen resistance progression.

Experimental Approach: In the present study, the expression of Notch pathway genes, including and the Notch downstream target was evaluated using quantitative RT-PCR in 36 tamoxifen-resistant (TAM-R) and 36 tamoxifen-sensitive (TAM-S) patients.

Protective Effects of Auraptene against Free Radical-Induced Erythrocytes Damage.

Objectives: Auraptene is the most abundant natural prenyloxycoumarin. Recent studies have shown that it has multiple biological and therapeutic properties, including antioxidant properties. Erythrocytes are constantly subjected to oxidative damage that can affect proteins and lipids within the erythrocyte membrane and lead to some hemoglobinopathies.

miR-27 and miR-124 target AR coregulators in prostate cancer: Bioinformatics and in vitro analysis.

The inadequate efficacy of the current treatments for metastatic prostate cancer has directed efforts to the discovery of novel therapies. MicroRNAs (miRNAs) have been considered potential therapeutic agents due to their ability to control gene expression and cellular pathways. The accurate identification of genes and pathways which are targeted by a miRNA is the first step in the therapeutic use of these molecules.

The Potential for Natural Products to Overcome Cancer Drug Resistance by Modulation of Epithelial-Mesenchymal Transition.

The acquisition of resistance and ultimately disease relapse after initial response to chemotherapy put obstacles in the way of cancer therapy. Epithelial-mesenchymal transition (EMT) is a biologic process that epithelial cells alter to mesenchymal cells and acquire fibroblast-like properties. EMT plays a significant role in cancer metastasis, motility, and survival.

Ellagitannins, promising pharmacological agents for the treatment of cancer stem cells.

Human tumors comprise subpopulations of cells called cancer stem cells (CSCs) that possess stemness properties. CSCs can initiate tumors and cause recurrence, metastasis and are also responsible for chemo- and radio-resistance. CSCs may use signaling pathways similar to normal stem cells, including Notch, JAK/STAT, Wnt and Hedgehog pathways.

Vaccines targeting angiogenesis in melanoma.

Angiogenesis has a significant role in metastasis and progression of melanoma. Even small tumors may be susceptible to metastasis and hence lead to a worse outcome in patients with melanoma. One of the anti-angiogenic treatment approaches that is undergoing comprehensive study is specific immunotherapy.

Role of and in the prognosis and tamoxifen resistance of estrogen receptor-positive breast cancer.

Despite the discovery of a number of different mechanisms underlying tamoxifen resistance, its molecular pathway is not completely clear. The upregulation of and has been reported in breast cancer. Nevertheless, their role in tamoxifen resistance has not been investigated.

Osteogenic induction of menstrual blood mesenchymal stem cell by different species extracts.

Objective: spp. have many applications in complementary medicine and are recognized as the most important sources of natural products for bone health and regeneration especially in postmenopausal women. Therefore, the aim of this study was to investigate the effects of the extracts from three species on proliferation and osteogenesis potential of human menstrual blood-derived mesenchymal stem cells (MenSCs).

The role of microRNAs on doxorubicin drug resistance in breast cancer.

Objectives: Resistance to chemotherapeutic drugs is a serious challenge for effective therapy of cancers. Doxorubicin is a drug which is typically used for breast cancer treatment. Several mechanisms are involved in resistance to doxorubicin including overexpression of ATP-binding cassette (ABC) transporters, altering apoptosis, autophagy and cell cycle arrest.

Glucosamine attenuates drug resistance in Mitoxantrone-resistance breast cancer cells.

Objectives: This study was aimed at investigating the cytotoxicity and multi-drug resistance (MDR) reversal effect of Glucosamine (GlcN) on resistant BCRP-overexpressing breast cancer MCF-7/MX cells.

Methods: After confirming the overexpression of BCRP, the cytotoxicity and MDR reversing potential of GlcN on MCF-7/MX mitoxantrone-resistant and MCF-7 sensitive breast cancer cells were assessed via MTT assay. The effects of GlcN on mitoxantrone accumulation were analyzed through flow cytometry.

promoter methylation and overexpression promote tamoxifen resistance in breast carcinoma patients.

Introduction: Disease recurrence is an important obstacle in estrogen receptor positive (ER) tamoxifen treated breast carcinoma patients. Tamoxifen resistance-related molecular mechanisms are not fully understood. Alteration in DNA methylation which contributes to transcriptional regulation of cancer-related genes plays a crucial role in tamoxifen response.

Association of Interleukin-10 -592 C > A gene polymorphism with coronary artery disease: A case-control study and meta-analysis.

Background: Coronary-artery-disease (CAD) is the leading cause of death worldwide, and hence there is a need to identify reliable markers for identifying individuals at high risk of developing CAD. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that is associated with an increased risk of developing both atherosclerosis and acute coronary events. The study aimed to explore the association of a genetic variant in IL-10 with the risk of developing CAD and the severity of the disease.

A DNA methylation panel for high performance detection of colorectal cancer.

One of the most promising ways to diagnose cancer especially colorectal cancer (CRC) is to trace its epigenetic events. In this article, a discovery step for detection of methylated DNA markers (MDMs) was performed using SureSelectXT Methyl-Seq in CRC case and control groups in addition to several methylation profiling datasets (GSE48684, GSE53051, GSE77718, GSE101764, and GSE42752). In silico validation of MDMs in colorectal and other cancers was conducted by Lnc2met.

Antisense Oligonucleotide (AS-ODN) Technology: Principle, Mechanism and Challenges.

Recently, there is a hopefully tremendous interest in antisense therapeutics for clinical purposes. Single-stranded synthetic antisense oligonucleotides (As-ODNs) with monomers of chemically modified 18-21 deoxynucleotides complement the mRNA sequence in target gene. The target gene expression can be blocked because of created cleavage or disability of the mRNA by binding the As-ODNs to cognate mRNA sequences via sequence-specific hybridization.

The role of noncoding RNAs and sirtuins in cancer drug resistance.

Cancer is a rising and major health issue around the world. The acquisition of resistance to chemotherapeutic drugs is a great obstacle for the effective treatment of nearly all cancers. Drug resistance is regulated by multiple factors and mechanisms including genetic mutations, abnormal expression of some cellular transporters such as multidrug resistance (MDR) transporters, changes in apoptotic pathways, cancer stem cells, tumor microenvironment, and noncoding RNAs (ncRNAs).

Glucosamine reverses drug resistance in MRP2 overexpressing ovarian cancer cells.

Glucosamine (GlcN), a natural amino sugar in human body, was reported to exhibit anticancer activity against some tumors. In the present study, we evaluated the cytotoxicity and multi-drug resistance (MDR) reversal activity of GlcN on resistant MRP2-overexpressing ovarian cancer A2780RCIS cells. The cytotoxicity and MDR reversal activity of GlcN on cancer cells were measured by MTT assay.