Oral Administration of Cancer Vaccines: Challenges and Future Perspectives.

Cancer vaccines, a burgeoning strategy in cancer treatment, are exploring innovative administration routes to enhance patient and medical staff experiences, as well as immunological outcomes. Among these, oral administration has surfaced as a particularly noteworthy approach, which is attributed to its capacity to ignite both humoral and cellular immune responses at systemic and mucosal tiers, thereby potentially bolstering vaccine efficacy comprehensively and durably. Notwithstanding this, the deployment of vaccines through the oral route in a clinical context is impeded by multifaceted challenges, predominantly stemming from the intricacy of orchestrating effective oral immunogenicity and necessitating strategic navigation through gastrointestinal barriers. Based on the immunogenicity of the gastrointestinal tract, this review critically analyses the challenges and recent advances and provides insights into the future development of oral cancer vaccines.

DNA damage response and breast cancer development: Possible therapeutic applications of ATR, ATM, PARP, BRCA1 inhibition.

Breast cancer is the most common and significant cancers in females regarding the loss of life quality. Similar to other cancers, one of the etiologic factors in breast cancer is DNA damage. A plethora of molecules are responsible for sensing DNA damage and mediating actions which lead to DNA repair, senescence, cell cycle arrest and if damage is unbearable to apoptosis. In each of these, aberrations leading to unrepaired damage was resulted in uncontrolled proliferation and cancer. Another cellular function is autophagy defined as a process eliminating of unnecessary proteins in stress cases involved in pathogenesis of cancer. Knowing their role in cancer, scholars have tried to develop strategies in order to target DDR and autophagy. Further, the interactions of DDR and autophagy plus their regulatory role on each other have been focused simultaneously. The present review study has aimed to illustrate the importance of DDR and autophagy in breast cancer according to the related studies and uncover the relation between DDR and autophagy and its significance in breast cancer therapy.

The critical roles of lncRNAs in the pathogenesis of melanoma.

Long non-coding RNAs (lncRNAs) embrace a huge fraction of human transcripts and participate in the pathogenesis of human disorders especially malignant conditions. Malignant melanoma, as the most fatal type of cutaneous malignnacies, is associated with dysregulation of several lncRNAs including PVT1, H19, MALAT1, and CCAT1. Moreover, a portion of lncRNAs are exclusively expressed in melanoma cell lines. Expression levels of several lncRNAs are associated with TNM stage, tumor size and progression of melanoma. Thus, these lncRNAs are regarded as biomarkers for this malignancy. Peripheral transcript levels of a number of lncRNAs, such as PVT1, SNHG5 and SPRY4-IT1, could distinguish melanoma patients from unaffected persons with appropriate sensitivity and specificity values. Moreover, expression levels of numerous lncRNAs in tissue biopsies could differentiate malignant samples from benign samples. Based on the results of both cell line and in vivo studies, lncRNAs regulate critical pathways in the carcinogenesis of melanoma, such as the PI3K/Akt and NF-κB signaling pathways, and are involved in the modulation of response to chemotherapeutic agents. Here we review the existing information on the role of lncRNAs in malignant melanoma.

miR-1: A comprehensive review of its role in normal development and diverse disorders.

MicroRNA-1 (miR-1) is a conserved miRNA with high expression in the muscle tissues. In humans, two discrete genes, MIRN1-1 and MIRN1-2 residing on a genomic region on 18q11.2 produce a single mature miRNA which has 21 nucleotides. miR-1 has a regulatory role on a number of genes including heat shock protein 60 (HSP60), Kruppel-like factor 4 (KLF4) and Heart And Neural Crest Derivatives Expressed 2 (HAND2). miR-1 has critical roles in the physiological processes in the smooth and skeletal muscles as well as other tissues, thus being involved in the pathogenesis of a wide range of disorders. Moreover, dysregulation of miR-1 has been noted in diverse types of cancers including gastric, colorectal, breast, prostate and lung cancer. In the current review, we provide the summary of the data regarding the role of this miRNA in the normal development and the pathogenic processes.

MicroRNAs as regulators of ERK/MAPK pathway: A comprehensive review.

The ERK/MAPK cascade is one the four distinctive MAPK cascades which transmit extracellular signals to intracellular targets. This cascade has an important role in the regulation of several fundamental processes such as proliferation, differentiation and cell response to diverse extrinsic stresses. Moreover, several studies have shown participation of this cascade in the pathogenesis of cancer. Recent investigations have unraveled interaction between microRNAs (miRNAs) and ERK/MAPK cascade. These transcripts reside in both upstream and downstream of this cascade, regulating or being regulated by ERK/MAPK proteins. In the current review, we summarize the role of miRNAs in the regulation of ERK/MAPK and their contribution in the pathogenesis of human disorders with particular focus on cancers.

Modulation of telomerase expression and function by miRNAs: Anti-cancer potential.

Telomerase is a nucleoprotein reverse transcriptase that maintains the telomere, a protective structure at the ends of the chromosome, and is active in cancer cells, stem cells, and fetal cells. Telomerase immortalizes cancer cells and induces unlimited cell division by preventing telomere shortening. Immortalized cancer cells have unlimited proliferative potential due to telomerase activity that causes tumorigenesis and malignancy. Therefore, telomerase can be a lucrative anti-cancer target. The regulation of catalytic subunit of telomerase (TERT) determines the extent of telomerase activity. miRNAs, as an endogenous regulator of gene expression, can control telomerase activity by targeting TERT mRNA. miRNAs that have a decreasing effect on TERT translation mediate modulation of telomerase activity in cancer cells by binding to TERT mRNA and regulating TERT translation. In this review, we provide an update on miRNAs that influence telomerase activity by regulation of TERT translation.

MicroRNAs and colorectal cancer chemoresistance: New solution for old problem.

BACKGROUND: Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies with a significant mortality rate. Despite the great advances in cancer treatment in the last few decades, effective treatment of CRC is still under challenge. One of the main problems associated with CRC treatment is the resistance of cancer cells to chemotherapy drugs. METHODS: Many studies have been carried out to identify CRC chemoresistance mechanisms, and shed light on the role of ATP-binding cassette transporters (ABC transporters), enzymes as thymidylate synthase, some signaling pathways, and cancer stem cells (CSC) in chemoresistance and failed CRC chemotherapies. Other studies have also been recently carried out to find solutions to overcome chemoresistance. Some of these studies have identified the role of miRNAs in chemoresistance of the CRC cells and the effective use of these micro-molecules to CRC treatment. RESULTS: Considering the results of these studies, more focus on miRNAs likely leads to a proper solution to overcome CRC chemoresistance. CONCLUSION: The current study has reviewed the related literature while discussing the efficacy of miRNAs as potential clinical tools for overcoming CRC chemoresistance and reviewing the most important chemoresistance mechanisms in CRC cells.

Downregulation of Cancer-Associated lncRNAs in Peripheral Blood of Multiple Sclerosis Patients.

Recent studies have shown contribution of long non-coding RNAs (lncRNAs) in the pathogenesis of immune-related disorders including multiple sclerosis (MS). Based on the role of these transcripts in the regulation of immune response, peripheral levels of lncRNAs can reflect the level of immune activation. In the present study, we quantified expression of four lncRNAs namely SPRY4-IT1, HOXA-AS2, LINC-ROR, and MEG3 in venous blood of MS patients and controls using quantitative real-time PCR method. Relative expressions of SPRY4-IT1, HOXA-AS2, LINC-ROR, and MEG3 were significantly lower in female MS patients compared with female healthy subjects. For MEG3, this pattern of expression was also observed in male subjects. However, for other lncRNAs, no significant difference was detected between male patients and male controls. Expression of HOXA-AS2 was correlated with progression index (r = 0.36, P < 0.001). Besides, there was a significant correlation between expression of this lncRNA and expression of LINC-ROR in MS patients (r = 0.44, P < 0.0001). There was no other correlation between expression of lncRNAs and clinical data in MS patients. In control group, expressions of none of lncRNAs were correlated with age of persons. Notably, significant correlations were demonstrated between expression levels of all lncRNAs in healthy subjects with r values ranging from 0.23 to 0.42. The current investigation shows dysregulation of lncRNAs in MS patients in a sex-specific manner and warrants further studies to unravel the clinical and therapeutic implications of such dysregulation.

miRNA-29a reverses P-glycoprotein-mediated drug resistance and inhibits proliferation via up-regulation of PTEN in colon cancer cells.

Colon cancer is a serious malignant type of cancer in the world. Acquisition of multi-drug resistance (MDR) during chemotherapy is still a controversial challenge during cancer treatment. Accordingly, detection of safe and impressive MDR-reversing targets such as microRNAs (miRNAs/miRs) can play critical role in cancer treatment. Here, the functional effects of miR-29a in chemo-resistant colon cancer cells is scrutinized. The effect of doxorubicin (DOX) on cell proliferation after miR-29a transfection has been evaluated using MTT assay in HT29 and HT29/DOX cells. Rhodamine123 (Rh123) assay is used to identify the activity of common drug efflux through membrane transporters P-glycoprotein (P-gp). P-gp and PTEN mRNA/protein expression levels were measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analyses. Flow cytometry was employed to the investigation of apoptosis. ANOVA followed by Bonferroni's and Sidak's tests were used to compare the data from different groups. Thus, it was shown that miRNA-29a overexpression considerably inhibited the HT29/DOX viability. miR-29a significantly down-regulated P-gp expression and activity in HT29/DOX cells and declined drug resistance through elevation of intracellular DOX. Furthermore, upon miRNA-29a transfection, PTEN expression could be restored in resistant cells. These results have indicated that miR-29a target PTEN ultimately P-gp, which is downstream of PTEN, inhibit drug resistance, proliferation, and apoptosis through PI3K/Akt pathway. As a result, miR-29a overexpression is led to enhance the sensitivity of HT29/DOX cells to DOX-treatment by targeting P-gp. MiR-29a might proffer a novel promising candidate for colon cancer therapeutics during chemotherapy.

Targeting PI3K/Akt/mTOR signaling pathway by polyphenols: Implication for cancer therapy.

Cancer is one of the biggest challenges facing medicine and its cure is regarded to be the Holy Grail of medicine. Therapy in cancer is consisted as various artificial cytotoxic agents and radiotherapy, and recently immunotherapy. Recently much attention has been directed to the use of natural occurring agents in cancer therapy. One of the main group of agents utilized in this regard is polyphenols which are found abundantly in berries, fruits and vegetables. Polyphenols show to exert direct and indirect effects in progression of cancer, angiogenesis, proliferation and enhancing resistance to treatment. One of the cellular pathways commonly affected by polyphenols is PI3K/Akt/mTOR pathway, which has far ranging effects on multiple key aspects of cellular growth, metabolism and death. In this review article, evidence regarding the biology of polyphenols in cancer via PI3K/Akt/mTOR pathway is discussed and their application on cancer pathophysiology in various types of human malignancies is shown.

A review on anti-cancer properties of Quercetin in breast cancer.

Breast cancer is one of the well-known malignant tumors among women. In spite of attempts to classifying breast cancer according to its histological and molecular properties, it is almost considered as a dilemma in treatment. Nowadays, public and medical attentions have primary focused on foods with anti-cancer properties to alleviate the cancer problems. Flavonoid components such as Quercetin (Qu) as dietary substances with high attention of ordinary people might provide potential of alternative or complementary medicine in breast cancer. With regard to the wide range of health benefits of Qu, researchers have been generally convinced to bring Qu as natural compounds in cancer therapy. Moreover, the high cost of standard cancer treatments and the failure of most conventional treatments have led the medical community to pursue cost-effective prevention and treatment. As a result, a great deal of concentration is attracted to diet/cancer reciprocal action. Therefore, this review study has aimed to identify what has revealed the critical properties of Qu such as anti-inflammatory, anti-oxidant, and even its effect on proliferation, angiogenesis, or apoptosis that are considered as anti-tumor property to enhance breast cancer treatment.

Human BCL10 Deficiency due to Homozygosity for a Rare Allele.

In 2014, a child with broad combined immunodeficiency (CID) who was homozygous for a private BCL10 allele was reported to have complete inherited human BCL10 deficiency. In the present study, we report a new BCL10 mutation in another child with CID who was homozygous for a BCL10 variant (R88X), previously reported as a rare allele in heterozygosis (minor allele frequency, 0.000003986). The mutant allele was a loss-of-expression and loss-of-function allele. As with the previously reported patient, this patient had complete BCL10 deficiency. The clinical phenotype shared features, such as respiratory infections, but differed from that of the previous patient that he did not develop significant gastroenteritis episodes or chronic colitis. Cellular and immunological phenotypes were similar to those of the previous patient. TLR4, TLR2/6, and Dectin-1 responses were found to depend on BCL10 in fibroblasts, and final maturation of T cell and B cell maturation into memory cells was affected. Autosomal-recessive BCL10 deficiency should therefore be considered in children with CID.

Critical roles of long noncoding RNAs in breast cancer.

Breast cancer is a major clinical challenge that affects a wide range of the female population and heavily burdens the health system. In the past few decades, attempts have been made to understand the etiology of breast cancer, possible environmental risk factors, and the genetic predispositions, pathogenesis, and molecular aberrations involved in the process. Studies have shown that breast cancer is a heterogeneous entity; each subtype has its specific set of aberrations in different cell signaling pathways, such as Notch, Wnt/ß-catenin, transforming growth factor-ß, and mitogen-activated protein kinase pathways. One novel group of molecules that have been shown to be inducted in the regulation of multiple cell signaling pathways is the long noncoding RNAs (lncRNAs). These molecules have important implications in the regulation of multiple signaling pathways by interacting with various genes, affecting the transcription process, and finally, playing roles in posttranslational control of these genes. There is growing evidence that lncRNAs are involved in the process of breast cancer formation by effecting the aforementioned signaling pathways, and that this involvement can have significant diagnostic and prognostic values in clinical contexts. The present review aims to elicit the significance of lncRNAs in the regulation of cell signaling pathways, and the resulting changes in cell survival, proliferation, and invasion, which are the hallmarks of breast cancer.

Overcoming multidrug resistance in cancer: Recent progress in nanotechnology and new horizons.

Multidrug resistance (MDR), defined as the ability of cancer cells to gain resistance to both conventional and novel chemotherapy agents, is an important barrier in treating malignancies. Initially, it was discovered that cellular pumps dependent on ATP were the cause of resistance to chemotherapy, and further studies have found that other mechanisms such as increased metabolism of drugs, decreased drug entry, and defective apoptotic pathways are involved in this process. MDR has been the focus of numerous initiatives and countless studies have been undertaken to better understand MDR and formulate strategies to overcome its effects. The current review highlights various nano-drug delivery systems including polymeric/solid lipid/mesoporous silica/metal nanoparticles, dendrimers, liposomes, micelles, and nanostructured lipid carriers to overcome the mechanism of MDR. Nanoparticles are novel gateways to enhance the therapeutic efficacy of anticancer agents at the target site of action due to their tumor-targeting abilities, which can limit the unwanted systemic effects of chemotherapy agents and also reduce drug resistance. Additionally, other innovative strategies including RNA interference as a biological process used to inhibit or silence specific gene expression, natural products as MDR modulators with little systemic toxic effects, which interfere with the functions of proteins involved in drug efflux, and physical approaches such as combination of conventional drug administration with thermal/ultrasound/photodynamic strategies are also highlighted.

MicroRNAs in breast cancer: Roles, functions, and mechanism of actions.

Breast cancer is one of the most lethal malignancies in women in the world. Various factors are involved in the development and promotion of the malignancy; most of them involve changes in the expression of certain genes, such as microRNAs (miRNAs). MiRNAs can regulate signaling pathways negatively or positively, thereby affecting tumorigenesis and various aspects of cancer progression, particularly breast cancer. Besides, accumulating data demonstrated that miRNAs are a novel tool for prognosis and diagnosis of breast cancer patients. Herein, we will review the roles of these RNA molecules in several important signaling pathways, such as transforming growth factor, Wnt, Notch, nuclear factor-κ B, phosphoinositide-3-kinase/Akt, and extracellular-signal-regulated kinase/mitogen activated protein kinase signaling pathways in breast cancer.

Targeting miRNAs by polyphenols: Novel therapeutic strategy for aging.

Regarding the importance of genetic and epigenetic factors in regulation of aging process, different expression pattern of non-coding RNAs in aging could be investigated. Accordingly, micro RNAs (miRNAs) with a wide range of physiological functions as well as a significant footprint in many diseases have been demonstrated to be down or upregulated during the aging process. Therefore, age-associated microRNAs and their targets have potentially detected the accelerated aging and predicted the risks for age-related diseases. Polyphenols as important antioxidants in human dietary observed in fruits and some beverages have beneficial effects on longevity and aging. Considering miRNAs as an interesting mediator in modulating polyphenols' biological effects, targeting miRNAs which is using polyphenols could be a novel strategy for aging.

Health-related Quality of Life and Associated Factors Among Thalassemia Major Patients, Southeast of Iran.

Low quality of life (QOL) is a feature that has been overlooked in thalassemia major (TM) patients. Our aim was to assess QOL in school-aged TM patients in Zabol city and surrounding rural areas in southeast of Iran. The study was performed in 2014. QOL was evaluated using Pediatric Quality of Life Inventory 4 (PedsQL4) questionnaire addressing physical, emotional, social, and educational, along with psychological health in 80 TM patients. Also, 80 age-matched and sex-matched subjects without any chronic illness served as control group. Mean age of the patients was 11.7±4.1 years old. Total QOL scores was 51.4±13.3 in the patients. In comparison, mean value of total QOL score in controls was 91.1±3.3 (P<0.0001). Poor and moderate QOL were observed in 44.7% and 48.7% of the patients, respectively. Mean functioning scores for physical, emotional, social, educational, and psychological dimensions in the patients were 56.2±119, 69.6.4±23.3, 27.1±22.1, 52.3±18.1, and 48.9±11.8, respectively. The lowest level of QOL was related to the social field (81.3% with less than average score), while the highest QOL was related to the emotional aspect (58.8% with good QOL; >75 scores). Overall, female sex, poor compliance with chelation therapy, and residency in urban areas were significantly associated with poor QOL. In conclusion, providing a psychiatric health package seems to be essential for improving QOL in TM patients, especially in social field.