Nanotechnological Advances in the Diagnosis of Gynecological Cancers and Nanotheranostics.

Gynecological cancers are one of the main causes of female mortality worldwide. Despite the various strategies to reduce mortality and improve quality of life, there are still many deficiencies in the diagnosis and treatment of gynecological cancers. One of the important steps to ensure optimal cancer treatment is the early detection of cancer cells and the use of drugs to reduce toxicity. Due to the increase in systemic toxicity and resistance to traditional and conventional diagnostic methods, new strategies, including nanotechnology, are being used to improve diagnosis and reduce the severity of the disease. Nanoparticles (NPs) provide exciting opportunities to improve Gynecological Cancers (GCs) diagnosis, particularly in the initial stages. In biomedical investigations and clinical settings, NPs can be used to increase the sensitivity and specificity of recognition and/or imaging of GCs with the help of their molecular and cellular processes. To design more efficient diagnostic NPs for gynecological cancer cells or tissues, determining the specific biomarkers is of great importance. NP-based imaging agents are another solution to trace cancer cells. This review highlights the potential of some NP-based diagnostic techniques in GC detection, which could be translated to clinical settings to improve patient care.

The Application of Nanotechnological Therapeutic Platforms against Gynecological Cancers.

Gynecological cancers (GCs), ovarian, cervical, and endometrial/uterine cancers, are often associated with poor outcomes. Despite the development of several therapeutic modalities against GCs, the effectiveness of the current therapeutic approaches is limited due to their side effects, low therapeutic index, short halflife, and resistance to therapy. To overcome these limitations, nano delivery-based approaches have been introduced with the potential of targeted delivery, reduced toxicity, controlled release, and improved bioavailability of various cargos. This review summarizes the application of different nanoplatforms, such as lipid-based, metal- based, and polymeric nanoparticles, to improve the chemo/radio treatments of GC. In the following work, the use of nanoformulated agents to fight GCs has been mentioned in various clinical trials. Although nanosystems have their own challenges, the knowledge highlighted in this article could provide deep insight into translations of NPs approaches to overcome GCs.

Recent Progress in the Application of Exosome Analysis in Ovarian Cancer Management.

Exosomes are very small (nano-sized) vesicles participating in tumor development by involvement in intercellular communication mediated by transferring biocomponents. Exosomes appear to play vital roles in various cancer development, such as ovarian cancer, a common malignancy in women. Several hallmarks of ovarian cancer are reported to be affected by the exosome-- mediated cellular cross-talk, including modulating peritoneal dissemination and chemoresistance. Since the expression of some biomolecules, such as miRNAs and mRNA, is changed in ovarian cancer, these exo-biomolecules can be applied as prognostic, diagnostic, and therapeutic biomarkers. Also, the selective loading of specific chemotherapeutic agents into exosomes highlights these biocarries as potential delivery devices. Exosomes could be artificially provided and engineered to better target the site of interest in ovarian cancer. In the present review, we summarize the notable achievement of exosome application in ovarian cancer management to gain applicable transitional insight against this cancer.

Current use of Molecular Mechanisms and Signaling Pathways in Targeted Therapy of Prostate Cancer.

Prostate cancer (PC) is identified as a heterogeneous disease. About 20 to 30% of PC patients experience cancer recurrence, characterized by an increase in the antigen termed serum prostate-specific antigen (PSA). Clinical recurrence of PC commonly occurs after five years. Metastatic castration-resistant prostate cancer (mCRPC) has an intricate genomic background. Therapies that target genomic changes in DNA repair signaling pathways have been progressively approved in the clinic. Innovative therapies like targeting signaling pathways, bone niche, immune checkpoint, and epigenetic marks have been gaining promising results for better management of PC cases with bone metastasis. This review article summarizes the recent consideration of the molecular mechanisms and signaling pathways involved in local and metastatic prostate cancer, highlighting the clinical insinuations of the novel understanding.

Insight into RNA-based Therapies for Ovarian Cancer.

Ovarian cancer (OC) is one of the most common malignancies in women and is associated with poor outcomes. The treatment for OC is often associated with resistance to therapies and hence this has stimulated the search for alternative therapeutic approaches, including RNA-based therapeutics. However, this approach has some challenges that include RNA degradation. To solve this critical issue, some novel delivery systems have been proposed. In current years, there has been growing interest in the improvement of RNAbased therapeutics as a promising approach to target ovarian cancer and improve patient outcomes. This paper provides a practical insight into the use of RNA-based therapeutics in ovarian cancers, highlighting their potential benefits, challenges, and current research progress. RNA-based therapeutics offer a novel and targeted approach to treat ovarian cancer by exploiting the unique characteristics of RNA molecules. By targeting key oncogenes or genes responsible for drug resistance, siRNAs can effectively inhibit tumor growth and sensitize cancer cells to conventional therapies. Furthermore, messenger RNA (mRNA) vaccines have emerged as a revolutionary tool in cancer immunotherapy. MRNA vaccines can be designed to encode tumor-specific antigens, stimulating the immune system to distinguish and eliminate ovarian cancer cells. A nano-based delivery platform improves the release of loaded RNAs to the target location and reduces the off-target effects. Additionally, off-target effects and immune responses triggered by RNA molecules necessitate careful design and optimization of these therapeutics. Several preclinical and clinical researches have shown promising results in the field of RNA-based therapeutics for ovarian cancer. In a preclinical study, siRNA-mediated silencing of the poly (ADP-ribose) polymerase 1 (PARP1) gene, involved in DNA repair, sensitized ovarian cancer cells to PARP inhibitors, leading to enhanced therapeutic efficacy. In clinical trials, mRNA-based vaccines targeting tumor-associated antigens have demonstrated safety and efficacy in stimulating immune responses in ovarian cancer patients. In aggregate, RNA-based therapeutics represent a promising avenue for the therapy of ovarian cancers. The ability to specifically target oncogenes or stimulate immune responses against tumor cells holds great potential for improving patient outcomes. However, further research is needed to address challenges related to delivery, permanence, and off-target effects. Clinical trials assessing the care and effectiveness of RNAbased therapeutics in larger patient cohorts are warranted. With continued advancements in the field, RNAbased therapeutics have the potential to develop the management of ovarian cancer and provide new hope for patients.

Epidemiological trends and risk factors of gynecological cancers: an update.

Gynecological cancers, the most common cancer among women worldwide, disrupt the function of women's reproductive system, significantly impacting the quality of life. The epidemiological patterns of gynecological cancers differ in various regions and alter over time. The main challenge to deal with women's cancers is focusing on potential plans to improve patient outcomes. The epidemiology and general risk elements of gynecological cancers are important in the management of these cancers, so all of the reported risk factors in gynecological cancers have been evaluated in the present review. Due to the role of gynecological cancers in women's health, preventive measures and modifiable lifestyles together with early detection in high-risk groups are effective strategies that can reduce mortality rates. This review summarizes the epidemiology and global risk factors of gynecological cancers alongside others to better management of these malignancies and improve the quality of life in the affected patients.

IL-33/ST2 axis in autoimmune disease.

Interleukin-33 (IL-33) is a member of the IL-1 family and plays an ambivalent role in autoimmune diseases. IL-33 signals via the ST2 receptor and drives cytokine production in mast cells, basophils, eosinophils, NK cells, and T lymphocyte cells. The vital role of IL-33 as an active component gives rise to aberrant local and systemic damage which has been demonstrated in numerous inflammatory disorders and immune-mediated pathological conditions including multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriasis, Sjogren's syndrome, inflammatory bowel disease (IBD), etc. IL-33/ST2 axis can up-regulate pro-inflammatory cytokine release in autoimmune disease, however, in some metabolic diseases like diabetes mellitus type 1 IL-33 can be considered an anti-inflammatory cytokine. The purpose of this review is to discuss selected studies on IL-33/ST2 axis in autoimmune diseases and its potential role as a pathogenic or protective cytokine.

Gynecologic Cancer, Cancer Stem Cells, and Possible Targeted Therapies.

Gynecologic cancer is one of the main causes of death in women. In this type of cancer, several molecules (oncogenes or tumor suppressor genes) contribute to the tumorigenic process, invasion, metastasis, and resistance to treatment. Based on recent evidence, the detection of molecular changes in these genes could have clinical importance for the early detection and evaluation of tumor grade, as well as the selection of targeted treatment. Researchers have recently focused on cancer stem cells (CSCs) in the treatment of gynecologic cancer because of their ability to induce progression and recurrence of malignancy. This has highlighted the importance of a better understanding of the molecular basis of CSCs. The purpose of this review is to focus on the molecular mechanism of gynecologic cancer and the role of CSCs to discover more specific therapeutic approaches to gynecologic cancer treatment.

miRNA-148b and its role in various cancers.

miRNA-148b belongs to the family miR-148/-152, with significant differences in nonseed sequences, which can target diverse mRNA molecules. Reportedly, it may undergo deregulation in lung and ovarian cancers and downregulation in gastric, pancreatic and colon cancers. However, there is a need for further studies to better characterize its mechanism of action and in different types of cancer. In this review, we focus on the aberrant expression of miR-148b in different cancer types and highlight its main target genes and signaling pathways, as well as its pathophysiologic role and relevance to tumorigenesis in several types of cancer.

Lay abstract miRNA-148b, or miR-148b, is a tumor suppressor that can regulate invasion-, apoptosis- and proliferation-related oncogenes. miR-148b prognostic and diagnostic potential has been the center of focus recent investigations and extensive studies have been performed on miR-148b regulation in carcinogenesis. Here, we review the role of miR-148b in various cancers and its potential therapeutic application as a target or biomarker.

Clinical significance of circulating tumor cell related markers in patients with epithelial ovarian cancer before and after adjuvant chemotherapy.

Circulating tumor cells (CTCs) have recently been considered as new prognostic and diagnostic markers for various human cancers; however, their significance in epithelial ovarian cancer (EOC) remains to be elucidated. In this study, using quantitative real-time PCR, we evaluated the expression of EPCAM, MUC1, CEA, HE4 and CA125 mRNAs, as putative markers of CTCs, in the blood of 51 EOC patients before and/or after adjuvant chemotherapy. Our results demonstrated that, before chemotherapy, the expression of EPCAM, MUC1, CEA and HE4 mRNAs were correlated to each other. CEA expression was correlated with tumor stage (r = 0.594, p = 0.000) before chemotherapy, whereas its expression after chemotherapy was correlated with serum levels of CA125 antigen (r = 0.658, p = 0.000). HE4 mRNA showed the highest sensitivity both before and after chemotherapy (82.98% and 85.19%, respectively) and the persistence of this marker after chemotherapy was associated with advanced disease stage. The expression of CA125 mRNA had negative correlation with the other markers and with tumor stage and therapy response (evaluated by the measurement of serum CA125 antigen). Collectively, our results indicated a better clinical significance of tumor-specific markers (CEA and HE4 mRNAs) compared to epithelial-specific markers (EPCAM and MUC1 mRNAs).

Recent advances and challenges of RT-PCR tests for the diagnosis of COVID-19.

Since the outbreak of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the control of virus spread has remained challenging given the pitfalls of the current diagnostic tests. Nevertheless, RNA amplification techniques have been the gold standard among other diagnostic methods for monitoring clinical samples for the presence of the virus. In the current paper, we review the shortcomings and strengths of RT-PCR (real-time polymerase chain reaction) techniques for diagnosis of coronavirus disease (COVID)-19. We address the repercussions of false-negative and false-positive rates encountered in the test, summarize approaches to improve the overall sensitivity of this method. We discuss the barriers to the widespread use of the RT-PCR test, and some technical advances, such as RT-LAMP (reverse-transcriptase-loop mediated isothermal amplification). We also address how other molecular techniques, such as immunodiagnostic tests can be used to avoid incorrect interpretation of RT-PCR tests.

Evaluation the interaction of ABC multidrug transporter MDR1 with thymoquinone: substrate or inhibitor?

OBJECTIVES: Thymoquinone (TQ) has valuable medical properties like anticancer effects. Development of multidrug resistance (MDR) phenotype is one of the most important factors in failure of cancer chemotherapy. The aim of this study was to evaluate the mode of interaction of TQ and MDR1, a major MDR-related protein in gastric cancer drug resistant EPG85-257RDB cells, and its parental non-resistant EPG85-257 cells. MATERIALS AND METHODS: MTT assay was used to assess the effects of TQ and doxorubicin (DOX) on cell viability of tested cell lines and TQ effect on pump performance. HPLC analyses were used to measure the input and output of TQ in EPG85-257RDB cells. Molecular docking studies were used to identify interactions between TQ and MDR1. RESULTS: TQ inhibited cell viability in a time and concentration-dependent manner. Co-treatment of the cells with TQ and DOX did not significantly affect the amount of cell viability in comparison with DOX treatment alone. The HPLC analyses showed that more than 90% of TQ entered to EPG85-257RDB during 1 hr of treatment with TQ, but it was unable to exit from the cells. Moreover, there was no difference between influx and efflux amount of TQ in cells with inhibited and non-inhibited MDR1 transporters. Molecular docking studies revealed that TQ had a higher inhibitory constant to bind to active site of MDR1 protein as compared to specific inhibitor (verapamil) and substrate (vinblastine) of this transporter. CONCLUSION: These results proposed that TQ does not work as an inhibitor or a substrate of MDR1 transporter.

The immunomodulatory effects of mesenchymal stromal cell-based therapy in human and animal models of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune inflammatory disease with no absolute cure. Although the exact etiopathogenesis of SLE is still enigmatic, it has been well demonstrated that a combination of genetic predisposition and environmental factors trigger a disturbance in immune responses and thereby participate in the development of this condition. Almost all available therapeutic strategies in SLE are primarily based on the administration of immunosuppressive drugs and are not curative. Mesenchymal stromal cells (MSCs) are a subset of non-hematopoietic adult stem cells that can be isolated from many adult tissues and are increasingly recognized as immune response modulating agents. MSC-mediated inhibition of immune responses is a complex mechanism that involves almost every aspect of the immune response. MSCs suppress the maturation of antigen-presenting cells (DC and MQ), proliferation of T cells (Th1, T17, and Th2), proliferation and immunoglobulin production of B cells, the cytotoxic activity of CTL and NK cells in addition to increasing regulatory cytokines (TGF-ß and IL10), and decreasing inflammatory cytokines (IL17, INF-ϒ, TNF-α, and IL12) levels. MSCs have shown encouraging results in the treatment of several autoimmune diseases, in particular SLE. This report aims to review the beneficial and therapeutic properties of MSCs; it also focuses on the results of animal model studies, preclinical studies, and clinical trials of MSC therapy in SLE from the immunoregulatory aspect.

Crocin Increases Gastric Cancer Cells' Sensitivity to Doxorubicin.

BACKGROUND: Crocin is one of the substantial constituents of saffron extract. It has multiple clinical effects including anti-cancer effects. The development of the multidrug resistance (MDR) phenotype is one of the principal causes of cancer chemotherapy failure. The multidrug resistance protein 1 (MDR1) is one of the MDR-related protein and is often overexpressed in different cancers. In the present study, we aimed to evaluate the influence of crocin on the expression and function of MDR1 protein in EPG85-257 and EPG85-257RDB gastric cancer cell lines. METHODS: The cytotoxicity effect of crocin was evaluated by the MTT assay. The impacts of crocin on the expression and function of MDR1 were assessed by Real-time RT-PCR and MTT assay, respectively. RESULTS: The results demonstrated that crocin decreased cell viability in a dose-dependent manner with higher intensity on the EPG85-257 than the EPG85-257RDB cells. Crocin did not make any significant changes in the MDR1 gene expression level in EPG85-257 and EPG85-257RDB cell lines. In contrast, crocin increased doxorubicin cytotoxicity in drug-resistant cells, which might be induced by reduced MDR1 activity. CONCLUSION: In summary, although crocin did not affect mRNA expression of MDR1, results of MTT assay suggest that it might inhibit the MDR1 function.

Ovarian cancer stem cells and targeted therapy.

BACKGROUND: Ovarian cancer has the highest ratio of mortality among gynecologic malignancies. Chemotherapy is one of the most common treatment options for ovarian cancer. However, tumor relapse in patients with advanced tumor stage is still a therapeutic challenge for its clinical management. MAIN BODY: Therefore, it is required to clarify the molecular biology and mechanisms which are involved in chemo resistance to improve the survival rate of ovarian cancer patients. Cancer stem cells (CSCs) are a sub population of tumor cells which are related to drug resistance and tumor relapse. CONCLUSION: In the present review, we summarized the recent findings about the role of CSCs in tumor relapse and drug resistance among ovarian cancer patients. Moreover, we focused on the targeted and combinational therapeutic methods against the ovarian CSCs.

Genetic and molecular bases of esophageal Cancer among Iranians: an update.

BACKGROUND: Esophageal cancer is one of the leading causes of cancer related deaths among the Iranians. There is still a high ratio of mortality and low 5 years survival which are related to the late onset and diagnosis. Majority of patients refer for the treatment in advanced stages of tumor progression. MAIN BODY: It is required to define an efficient local panel of diagnostic and prognostic markers for the Iranians. Indeed such efficient specific panel of markers will pave the way to decrease the mortality rate and increase the 5 years survival among the Iranian patients via the early diagnosis and targeted therapy. CONCLUSION: in present review we have reported all of the molecular markers in different signaling pathways and cellular processes which have been assessed among the Iranian esophageal cancer patients until now.