Circulating microRNA-133, microRNA-17 and microRNA-25 in serum and its potential diagnostic value in gastric cancer.

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.

Knockdown of Sal-like 4 expression by siRNA induces apoptosis in colorectal cancer.

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.

Current status and future prospects of transforming growth factor-ß as a potential prognostic and therapeutic target in the treatment of breast cancer.

The transforming growth factor-ß (TGF-ß) 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-ß 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-ß signaling pathway. This study attempts to summarize the current data about the functions of TGF-ß 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.

Expression of circulating miR-17, miR-25, and miR-133 in breast cancer patients.

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.

Therapeutic potency of Wnt signaling antagonists in the pathogenesis of prostate cancer, current status and perspectives.

Prostate cancer is a major cause of cancer-related death in males. Wnt/ß-catenin signaling plays a critical role in the pathogenesis of this disease by regulating angiogenesis, drug resistance, cell proliferation, and apoptosis. Suppression of Wnt canonical or noncanonical signaling pathways via Wnt biological or pharmacological antagonists is a potentially novel therapeutic approach for patients with prostate cancer. This review summarizes the role of Wnt signaling inhibitors in the pathogenesis of prostate cancer for a better understanding and hence a better management of this disease.

The potential therapeutic use of renin-angiotensin system inhibitors in the treatment of inflammatory diseases.

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 (AT1 ) receptor, and direct renin inhibitors, angiotensin-converting enzyme (ACE) inhibitors and AT1 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.

Chemopreventive and therapeutic potential of curcumin in esophageal cancer: Current and future status.

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.

Evaluation of the two polymorphisms rs1801133 in MTHFR and rs10811661 in CDKN2A/B in breast cancer.

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.

Berberine: A potential adjunct for the treatment of gastrointestinal cancers?

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.

Stem cell- and gene-based therapies as potential candidates in Alzheimer's therapy.

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.

Effects of curcumin on NF-κB, AP-1, and Wnt/ß-catenin signaling pathway in hepatitis B virus infection.

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/ß-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/ß-catenin signaling) which affected by curcumin in HBV infections.

Anti-Cancer and Radio-Sensitizing Effects of Curcumin in Nasopharyngeal Carcinoma.

Nasopharyngeal Cancer (NPC) is a rare type of head and neck cancer that is mainly treated by radiotherapy, but sometimes it is radioresistant. Curcumin is a polyphenolic natural product with established anticancer effects in various human cancers. Recent studies have shown that curcumin has therapeutic and radiosensitizing effects on NPC cells. In fact, it has been found that curcumin can sensitize NPC cells to radiation through different mechanisms, including modulation of ROS generation, Jab1/CSN5 and non-coding RNAs. As curcumin is safe and lacks systemic toxic effects in humans, it may be considered as a potential candidate to enhance the therapeutic effects of radiation and potentiate the efficacy of chemotherapy in the context of combination regimens.

Expression of microRNAs and IRAK1 pathway genes are altered in gastric cancer patients with Helicobacter pylori infection.

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.

Tumor-derived exosomes: Potential biomarker or therapeutic target in breast cancer?

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.

The therapeutic potential of targeting the BRAF mutation in patients with colorectal cancer.

Colorectal cancer is among the most lethal malignancies globally. BRAF is a member of the RAS/RAF/MEK/ERK signaling pathway. Its constitutive activation can result in increased cellular growth, development, invasion, and resistance to therapy. A mutation of the BRAF gene is present in 5-10% of metastatic colorectal cancers. BRAF mutations have been found to predict a lack of benefit to anti-EGFR therapy in metastatic CRC. Furthermore, CRC containing the BRAF V600E mutation display an innate resistance to BRAF inhibitors. The mechanisms of cell resistance can be explained at least in part by ERK dependent and ERK in-dependent pathway. Clinical trials evaluating the combinations of BRAF, PI3K, EGFR, and/or MEK inhibitors have revealed promising activity in BRAF mutant containing CRCs. There may be some benefit from future studies that focus on improving the efficacy of combined therapy in CRC with respect to the sustained effects. The aim of current review is to give an overview about the current status and prospective regarding the therapeutic potential of targeting BRAF mutant colorectal cancer.

The cross-regulation between SOX15 and Wnt signaling pathway.

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.