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Gastric cancer is one of the most common malignancies in the world and is considered as the most lethal gastrointestinal cancer. microRNAs (miRNAs) can be very important in detecting a disease at an early stage. The aim of this study was to investigate the microRNA-17 (miR-17), miR-25, and miR-133b in the serum of gastric cancer subjects. Serum samples were obtained from 120 gastric cancers and 102 healthy subjects. We evaluated expression levels of miR-17, miR-25 and miR-133b by quantitative real-time polymerase chain reaction. Our results showed that in the patients with gastric cancer, the expression level of miR-17 and miR-25 were significantly increased compared with the control group (P < 0.5), while the expression level of miR-133b was significantly decreased in patient groups compared with control cases (P < 0.5). It seems that expression of miRNAs in Iranian patients with gastric cancer is similar to other patients in other populations. These findings suggested that miR-17, miR-25 and miR-133b could be introduced as potential diagnostic candidates for the detection in gastric cancer patients in the early stage., (© 2019 Wiley Periodicals, Inc.)

Colorectal cancer (CRC) is known as the third most common malignancies among men and women and is also the second leading cause of cancer-related deaths worldwide. It has been indicated that a variety of risk factors are involved in the pathogenesis of CRC. Spalt-like transcription factor 4 (SALL4) is known as a transcription factor that plays an important role in the proliferation of cancerous cells. In this study, using a specific sequence of small interfering RNA (siRNA) against the sequence of SALL4, its activity is investigated in the CRC cell line (sw742). The CRC cells (sw742) were cultured and then, using a specific anti-SALL4 siRNA, their toxic doses were determined. Then, the gene is transfected into the cell. Proliferation and expression of the SALL4 and Bcl-2 gene were measured using the real-time polymerase chain reaction method. Cell death was evaluated by propidium iodide staining and fluorescence-activated cell sorting analysis. Our results indicated that the specific concentration of siRNA of the SALL4 gene was 62.5 nmole. Gene expression of SALL4 and Bcl-2 results showed that expression of Bcl-2 gene in the siRNA group was significantly reduced. In conclusion, our finding indicated that it could be used as a therapeutic and diagnostic biomarker in the treatment of patients with CRC., (© 2019 Wiley Periodicals, Inc.)

Curcumin is a polyphenolic compound derived from Curcumin longa L. There are growing bodies of evidence revealing the antitumor effect of curcumin in different tumors; although the molecular mechanism behind this inhibition in glioblastoma multiform (GBM) still remains unclear. Here we investigated the antitumor activity of nano micelles curcumin compared with erlotinib in U-373 cells in monolayer cell cultures and spheroids models. Furthermore, we characterized affecting cell cycle perturbation, as well as apoptosis induction in GBM cells. The antiproliferative activity of nano micelles curcumin and erlotinib were assessed in monolayer and spheroid models. The influence of the cell cycle and expression levels of nuclear factor κB (NF-κB) and Wnt/β-catenin pathway was checked. Nano micelles curcumin suppressed cell growth in U-373 cells via modulation of Wnt and NF-κB pathways. Moreover, cells developed an early G2/M cell cycle arrest followed by sub-G1 apoptosis and apoptotic bodies formation posttreatment with nano micelles curcumin and erlotinib. In the core signaling pathways of GBM, nano micelles curcumin either significantly influences the NF-κB pathway by decreasing p-65 expression or significantly inhibits the Wnt/β-catenin pathway by declining cyclin D1 expression. In conclusion, we have shown that nano micelles curcumin effectively prevent proliferation, and invasion of GBM cells through perturbation of Wnt/β-catenin and NF-κB pathways, suggesting further investigations on the therapeutic application of this novel anticancer drug in in vivo models., (© 2018 Wiley Periodicals, Inc.)

Colorectal cancer (CRC) is known as the third most common and fourth leading cancer associated death worldwide. The occurrence of metastasis has remained as a critical challenge in CRC, so that distant metastasis (mostly to the liver) has been manifested in about 20%-25% of patients. Several screening approaches have introduced for detecting CRC in different stages particularly in early stages. The standard treatments for CRC are surgery, chemotherapy and radiotherapy, in alone or combination. Immunotherapy is a set of novel approaches with the aim of remodeling the immune system battle with metastatic cancer cells, such as immunomodulatory monoclonal antibodies (immune checkpoint inhibitors), adoptive cell transfer (ACT) and cancer vaccine. Cancer vaccines are designed to trigger the intense response of immune system to tumor-specific antigens. In two last decades, introduction of new cancer vaccines and designing several clinical trials with vaccine therapy, have been taken into consideration in colon cancer patients. This review will describe the treatment approaches with the special attention to vaccines applied to treat colorectal cancer., (© 2018 Wiley Periodicals, Inc.)

Breast cancer is the most prevalent cancers worldwide and causes a significant amount of deaths annually. Spalt-like transcription factor 4 is known as a transcription factor, which has an important role in the proliferation of cancerous cells. Small interfering RNA (siRNA) is a short-chain molecule of 20 to 25 nucleotides that protrude on two sides of the 3', two nucleotides. In this study, using a specific sequence of siRNA against the sequence of this gene, its activity is investigated in the cell line of breast cancer. The breast cancer cells (MCF-7) were cultured and then, using a specific anti-sal-like 4 (SALL4) siRNA, their toxic doses were determined. Then, the gene is transfected into the cell. Proliferation and expression of the SALL4 and BCL-2 gene were measured using the real-time polymerase chain reaction method. The specific concentration of siRNA IC 50 of the SALL4 gene was 40.35 nmole. Gene expression results indicated that the expression of the Bcl-2 gene in the siRNA group was significantly reduced ( P < 0.05). SiRNA can increase the apoptosis of breast cancer cells by reducing the gene expression of SALL4 gene and Bcl-2; it can be used as a novel targeted therapy. This strategy, in addition to increasing the specificity of the drug, also reduces the side effects when compared with conventional chemotherapy., (© 2018 Wiley Periodicals, Inc.)

The transforming growth factor-β (TGF-β) signaling pathway is one of the important pathways involved in the cancer cell proliferation, invasion, migration, angiogenesis, apoptosis, as well as in metastasis by agitation or invasion of metastasis-related factors, including matrix metalloproteinase (MMP), epithelial-to-mesenchymal transition (EMT), tumor microenvironment (TME), cancer stem cells (CSCs), and cell adhesion molecules (CAMs). These data suggest its potential value as a therapeutic object in the treatment of malignancies including breast cancer. Several pharmacological approaches have been established to suppress TGF-β pathway; such as vaccines, small molecular inhibitors, antisense oligonucleotides, and monoclonal antibodies. Some of these are now approved by the US Food and Drug Administration for targeting the TGF-β signaling pathway. This study attempts to summarize the current data about the functions of TGF-β in cancer cells, and their probable application in the cancer therapy with a specific emphasis on recent preclinical and clinical research in the treatment of breast cancer and its prognostic value., (© 2019 Wiley Periodicals, Inc.)

One of the most lethal cancers among women is breast cancer. MicroRNAs (miRNAs) can be of great importance in the early detection of breast cancer. This study aimed to investigate some miRNAs in the serum of patients with breast cancer compared with the control group. Total RNA was extracted from the serum of patients with breast cancer and healthy volunteers. The expression levels of miRNAs and the genes were assessed using real-time reverse transcriptase-polymerase chain reaction with specific primers. Our data showed that miR-25 and miR-133 were downregulated, and miR-17 was upregulated in patients with breast cancer. Upregulation of miR-17 is related to the poor survival time and increased cell proliferation. The reduced expression of miR-133 and miR-25 is significantly associated with clinical stage, metastasis, and survival time of patients with breast cancer. Expressions of miRNAs miR-17, miR-25, and miR-133 are altered in patients with clinical stage, metastasis, poor survival time., (© 2018 Wiley Periodicals, Inc.)

Esophageal cancer is a common malignant tumor with an increasing trend during the past three decades. Currently, esophagectomy, often in combination with neoadjuvant chemo- and radiotherapy, is the cornerstone of curative treatment for esophageal cancer. However, esophagostomy is related to significant risks of perioperative mortality and morbidity, as well as lengthy recovery. Moreover, the adjuvant therapies including chemotherapy and radiotherapy are associated with numerous side effects, limiting compliance and outcome. The dietary agent curcumin has been extensively studied over the past few decades and is known to have many biological activities especially in regard to the prevention and potential treatment of cancer. This review summarizes the chemo-preventive and chemotherapeutic potential of curcumin in esophageal cancer in both preclinical and clinical settings., (© 2018 UICC.)

Inflammation is a normal part of the immune response to injury or infection but its dysregulation promotes the development of inflammatory diseases, which cause considerable human suffering. Nonsteroidal anti-inflammatory agents are the most commonly prescribed agents for the treatment of inflammatory diseases, but they are accompanied by a broad range of side effects, including gastrointestinal and cardiovascular events. The renin-angiotensin system (RAS) is traditionally known for its role in blood pressure regulation. However, there is increasing evidence that RAS signaling is also involved in the inflammatory response associated with several disease states. Angiotensin II increases blood pressure by binding to angiotensin type 1 (AT 1 ) receptor, and direct renin inhibitors, angiotensin-converting enzyme (ACE) inhibitors and AT 1 receptor blockers (ARBs) are clinically used as antihypertensive agents. Recent data suggest that these drugs also have anti-inflammatory effects. Therefore, this review summarizes these recent findings for the efficacy of two of the most widely used antihypertensive drug classes, ACE inhibitors and ARBs, to reduce or treat inflammatory diseases such as atherosclerosis, arthritis, steatohepatitis, colitis, pancreatitis, and nephritis., (© 2018 Wiley Periodicals, Inc.)

The 5,10-Methylenetetrahydrofolate reductase (MTHFR) was the rate-limiting enzyme in the methyl cycle, which was encoded by the MTHFR gene. MTHFR played a key role in homocysteine plasma level and was associated with the risk of breast cancer. The cyclin-dependent kinase (CDK) inhibitor (CDKN2A/B) was the tumor suppressor in the cell cycle regulation. The single-nucleotide polymorphism was thought to be associated with the predisposition of breast cancer and in subsequent immune response in different populations. The current study was conducted on a peripheral blood sample of 100 Iranian women with breast carcinoma and 142 cancer-free healthy female volunteers. The TaqMan real-time polymerase chain reaction technique was applied for genotyping of participants. The correlation of both variants and demographic data were investigated with the risk of breast cancer. Our data showed that the MTHFR allele T and TT genotype had the higher prevalence in patients (P < 0.0001) than the control group. The frequency of risk C allele into the CDKN2A/B rs10811661 was 72%. The correlations of menarche and underlying hormonal disorder with the risk of breast cancer were investigated; also our results showed that the menopause status was statistically significant between patients and controls (P = 0.036). Our investigations demonstrated that the MTHFR rs180113 and CDKN2A/B rs10811661 had a significant correlation with the elevated risk of breast cancer and they might be potentially valuable to apply as a prognostic factor for individual health care., (© 2018 Wiley Periodicals, Inc.)

Gastrointestinal cancers are among the most prevalent cancers in the general population. Despite effective early diagnostics and intervention, the gastrointestinal cancer-related mortality still remains elevated. Berberine (BBR) is a benzyl tetra isoquinoline alkaloid exracted from several plants. BBR is nontoxic to human normal cells, but suppresses the growth of different tumor cells: melanoma, epidermoid carcinoma, hepatoma, oral carcinoma, glioblastoma, prostatic carcinoma, and gastric carcinoma. In particular, BBR seems to suppress the proliferation of gastrointestinal cancers in a number of preclinical models. Several mechanisms of action have been hypothesized and demonstrated: immunomodulation, inhibition of topoisomerase enzymes, suppression of the EGF receptor, Her2/neu, and the VEGF receptor, induction of p53, Cip1/p21, Kip1/p27, Rb expression, induction of apoptosis (by regulation of MMPs pathway, caspases, Bax, and Smac/DIABLO), inhibition of arylamin N-acetyltransferase activity, and regulation of microRNAs expression. The aim of this review is to summarize the pharmacological effects of BBR on animal and human gastrointestinal cancers., (© 2018 Wiley Periodicals, Inc.)

Curcumin is a yellow-orange powder derived from the Curcuma longa plant. Curcumin has been used extensively in traditional medicine for centuries. This component is non-toxic and shown different therapeutic properties such as anti-inflammatory, anti-cancer, antiviral, anti-bacterial, anti-fungal, anti-parasites, and anti-oxidant. Hepatitis B virus (HBV) is a small DNA member of the genus Orthohepadnavirus (Hepadnaviridae family) which is a highly contagious blood-borne viral pathogen. HBV infection is a major public health problem with 2 billion people infected throughout the world and 350 million suffering from chronic HBV infection. Increasing evidence indicated that curcumin as a natural product could be employed in the treatment of HBV patients. It has been showed that curcumin exerts its therapeutic effects on HBV patients via targeting a variety of cellular and molecular pathways such as Wnt/β-catenin, Ap1, STAT3, MAPK, and NF-κB signaling. Here, we summarized the therapeutic effects of curcumin on patients who infected with HBV. Moreover, we highlighted main signaling pathways (eg, NF-κB, AP1, and Wnt/β-catenin signaling) which affected by curcumin in HBV infections., (© 2018 Wiley Periodicals, Inc.)

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, which is associated with impairments of memory, thinking, language, and reasoning. Despite extensive research aiming at the treatment of AD, durable and complete remissions are rare. Hence, new therapeutic approaches are required. Among various therapeutic approaches, stem cells (ie, neural stem cells, mesenchymal stem cells, and embryonic stem cells) and delivery of protective genes such as encoding nerve growth factor, APOE, and glial cell-derived neurotrophic factor have generated promise in AD therapy. Here, we summarized a variety of effective therapeutic approaches (ie, stem cells, and genes) in AD therapy., (© 2018 Wiley Periodicals, Inc.)

Gastric cancer (GC) is among the most common cancer types in the world and one of the most lethal gastrointestinal cancers. MicroRNAs (miRNAs) can be of great importance in the early detection of GC. This study aimed to investigate some miRNAs and the genes involved in IRAK1 pathways in the serum of GC patients with Helicobacter pylori (H. pylori) infections compared to the control group. Total RNA was extracted from the serum of GC patients with H. pylori infection and healthy volunteers. The expression levels of miRNAs and the genes were assessed using Real time RT-PCR with specific primers. Our data showed that miR-146, miR-375, and Let-7 were down-regulated and miR-19 and miR-21 were up-regulated in GC patients with H. pylori infection. Other genes involved in the pathways such as RAS, MYC, NFKB, JUN, TRAF6, and IRAK4 were overexpressed; while the expression of PTEN gene was decreased compared to the control group. Expression of miRNAs and IRAK1 pathway genes are altered in patients with GC and H. pylori infection. This suggests a potential role for the above-mentioned miRNAs and genes in the diagnosis of GC., (© 2018 Wiley Periodicals, Inc.)

Exosomes are released by normal and tumour cells, including those involved in breast cancer, and provide a means of intercellular communications. Exosomes with diameters ranging between 30-150 nm are involved in transferring biological information, via various lipids, proteins, different forms of RNAs, and DNA from one cell to another, and this can result in reprogramming of recipient cell functions. These vesicles are present in all body fluids, for example, blood plasma/serum, semen, saliva, cerebrospinal fluid, breast milk, and urine. It has been recently reported that these particles are involved in the development and progression of different tumor types, including breast cancer. Furthermore, it has been suggested that exosomes have the potential to be used as drug transporters, or as biomarkers. This review highlights the potential roles of exosomes in normal and breast cancer cells and their potential applications as biomarkers with special focus on their potential applications in treatment of breast cancer., (© 2017 Wiley Periodicals, Inc.)

Pyrvinium pamoate (PP) is a quinoline-derived cyanine dye which was officially approved by FDA for its anthelmintic properties and therapeutic function against animal-like protists such as Cryptosporidium parvum and Plasmodium falciparum in the 1950s. In the last 10 years, several studies have shown the novel activity of pyrvinium in tumor therapy. Some investigations have indicated that pyrvinium could delay or inhibit tumor cell proliferation in cancer models including colon, breast, lung and prostate cancer, and some hematological malignancies. In this review, we discuss multiple critical signaling pathways and mechanisms underlying the anticancer effects of PP. In details, pyrvinium acts through the following main mechanisms: (i) energy and autophagy depletion; and (ii) inhibition of Akt and Wnt-β-catenin-dependent pathways. Interestingly, pyrvinium has also shown potent anti-cancer stem cell activity. The overwhelming insights into the mechanism of anticancer properties of PP can help establishing novel and future anti-tumor treatment strategies., (© 2017 Wiley Periodicals, Inc.)

WNT/B-CATENIN signaling pathway is one of the key dysregulated pathways in different tumor types, which regulate the expression of several genes involved in cell proliferation, differentiation, and survival. This pathway is being modulated by sex-determining region Y-box (SOX) family genes. The functions of these genes are suggested as tumor suppressor or oncogene. SOX genes transcribe a group of transcription factors that play important roles in embryonic development and carcinogenesis. Among them, SOX15 is recently been identified as a novel tumor suppressor in pancreatic and esophagus cancers with a potential role in modulating Wnt/b-catenin signaling. This report summarizes the current knowledge about Wnt/b-catenin signaling pathway and its cross talk with SOX15 with particular emphasis on the value of SOX gene expression as prognostic or predictive biomarker in cancer., (© 2017 Wiley Periodicals, Inc.)