Optical-based biosensor for detection of oncomarker CA 125, recent progress and current status.

Ovarian cancer (OV) is the second most mortal gynecological malignancy. The oncomarker CA125 has been used as the main ovarian cancer marker for diagnosing and screening ovarian cancer in stages I and II. Therefore, sensitive and real-time detection of CA 125 is critical in ovarian cancer monitoring. Various tests are used to diagnose the CA 125. In recent years, modern methods such as biosensor technology have replaced the old tests for rapid, sensitive and specific detection of CA 125. Various types of biosensors are being developed, among which Surface Plasmon resonance (SPR) biosensors are one of the most important and remarkable types. Considering the importance of SPR biosensors in the diagnosis of enocomarker CA 125, the main focus of the present study is to consolidate the research work from the past two decade to the present. Also, the advantages and challenges in SPR biosensors development have been considered in the detection of CA 125 oncomarker.

Tumor immunotherapies by immune checkpoint inhibitors (ICIs); the pros and cons.

The main breakthrough in tumor immunotherapy was the discovery of immune checkpoint (IC) proteins, which act as a potent suppressor of the immune system by a myriad of mechanisms. After that, scientists focused on the immune checkpoint molecules mainly. Thereby, much effort was spent to progress novel strategies for suppressing these inhibitory axes, resulting in the evolution of immune checkpoint inhibitors (ICIs). Then, ICIs have become a promising approach and shaped a paradigm shift in tumor immunotherapies. CTLA-4 plays an influential role in attenuation of the induction of naïve and memory T cells by engagement with its responding ligands like B7-1 (CD80) and B7-2 (CD86). Besides, PD-1 is predominantly implicated in adjusting T cell function in peripheral tissues through its interaction with programmed death-ligand 1 (PD-L1) and PD-L2. Given their suppressive effects on anti-tumor immunity, it has firmly been documented that ICIs based therapies can be practical and rational therapeutic approaches to treat cancer patients. Nonetheless, tumor inherent or acquired resistance to ICI and some treatment-related toxicities restrict their application in the clinic. The current review will deliver a comprehensive overview of the ICI application to treat human tumors alone or in combination with other modalities to support more desired outcomes and lower toxicities in cancer patients. Video Abstract.

Shining the light on clinical application of mesenchymal stem cell therapy in autoimmune diseases.

The autoimmune diseases are associated with the host immune system, chronic inflammation, and immune reaction against self-antigens, which leads to the injury and failure of several tissues. The onset of autoimmune diseases is related to unbalanced immune homeostasis. Mesenchymal stem cells (MSCs) are multipotent cells which have capability to self-renew and differentiate into various cell types that exert a critical role in immunomodulation and regenerative therapy. Under the certain condition in vitro, MSCs are able to differentiate into multiple lineage such as osteoblasts, adipocytes, and neuron-like cells. Consequently, MSCs have a valuable application in cell treatment. Accordingly, in this review we present the last observations of researches on different MSCs and their efficiency and feasibility in the clinical treatment of several autoimmune disorders including rheumatoid arthritis, type 1 diabetes, multiple sclerosis, systemic lupus erythematosus, inflammatory bowel disease, autoimmune liver disease, and Sjogren's syndrome.

Quality of life, anxiety and depressive disorders in patients with extrasystolic arrhythmia.

Introduction: The aim of this study was to perform a comparative and economic analysis of the degree of development of anxiety-depressive disorder in patients with different types of extrasystolic arrhythmia using different assessment scales. Material and methods: The study was conducted in 2018-2019 at the premises of clinic No. 4, involving 450 patients (Moscow, Russia). Patients were divided into three groups: with coronary heart disease (CHD) (147 patients), with myocardiodystrophy (MCD) (113) and with cardiopsychoneurosis (CPN) (190). Everyone underwent round-the-clock electrocardiography (ECG) and echocardiography. If symptoms of depressive disorder are detected in a timely manner, the risk of adverse cardiovascular diseases may be reduced. Results: Depression and anxiety indicators on all three scales differed significantly (p ≤ 0.05) in patients with supraventricular extrasystole (more than 40 points on the Zung scale, 14 points on the Montgomery-Asberg depression scale, more than 38 points on Zung and 3 points on Covi anxiety scales). For patients with ventricular extrasystole, a significant difference was established between groups 1 and 2 only in terms of the level of depression on the Zung scale. Factors of psychogenic origin determine the development of cardiac rhythm disturbances. Conclusions: The study showed that for supraventricular extrasystoles, these factors determine the overall health of the patient. The differences between the three groups are significant on all scales of depression and anxiety (p ≤ 0.05). The most susceptible to depression and anxiety are patients with extrasystolic arrhythmias diagnosed with CHD, as well as MCD.

Mesenchymal stromal/stem cells and their exosomes application in the treatment of intervertebral disc disease: A promising frontier.

Today, the application of mesenchymal stromal/stem cells (MSCs) and their exosomes to treat degenerative diseases has received attention. Due to the characteristics of these cells, such as self-renewability, differentiative and immunomodulatory effects, their use in laboratory and clinical studies shows promising results. However, the allogeneic transplantation problems of MSCs limit the use of these cells in the clinic. Scientists propose the application of exosomes to use from the therapeutic effect of MSCs and overcome their defects. These vesicles change the target cell behaviour and transcription profile by transferring various cargo such as proteins, mi-RNAs, and lipids. One of the degenerative tissue diseases in which MSCs and their exosomes are used in their treatment is intervertebral disc disease (IDD). Different factors such as genetics, nutrition, ageing, and environmental factors play a significant role in the onset and progression of this disease. These factors affect the cellular and molecular properties of the disc, leading to tissue destruction. Nucleus pulposus cells (NPCs) are among the most important cells involved in the pathogenesis of disc degeneration. MSCs exert their therapeutic effects by differentiating, reducing apoptosis, increasing proliferation, and decreasing senescence in NPCs. In addition, the use of MSCs and their exosomes also affects the annulus fibrosus and cartilaginous endplate cells in disc tissue and prevents disc degeneration progression.

Immunotherapy of multisystem inflammatory syndrome in children (MIS-C) following COVID-19 through mesenchymal stem cells.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new type of coronavirus causing coronavirus 2019 (COVID-19) that was first observed in Wuhan, China, in Dec. 2019. An inflammatory immune response targeting children appeared during the pandemic, which was associated with COVID-19 named multisystem inflammatory syndrome in children (MIS-C). Characteristics of MIS-C include the classic inflammation findings, multi-organ dysfunction, and fever as the cardinal feature. Up to now, no specific therapy has been identified for MIS-C. Currently, considerable progress has been obtained in the MIS-C treatment by cell therapy, specially Mesenchymal stem cells (MSCs). Unique properties have been reported for MSCs, such as various resources for purification of cell, high proliferation, self-renewal, non-invasive procedure, tissue regenerator, multidirectional differentiation, and immunosuppression. As indicated by a recent clinical research, MSCs have the ability of reducing disease inflammation and severity in children with MIS-C. In the present review study, the benefits and characteristics of MSCs and exosomes are discussed for treating patients with MIS-C.

Psychodiagnostics as a Mandatory Element of Patient Protocols in Dentistry.

OBJECTIVES: This study aims at performing psychodiagnostics of the patients` condition with removable and fixed dentures both before and after dental treatment. MATERIALS AND METHODS: The first group included 200 patients with fixed-type dentures, and the second group consisted of 200 patients with removable dental devices. The control group included 200 patients with healthy teeth. All patients were subjected to Fere's skin-galvanic reaction procedure. Patients also filled out the Dental Status Questionnaire and were then tested following the Spielberger-Hanin Scale. For a comparison of differences, a two-sample t-test for independent samples was used. The Pearson correlation between features was calculated considering their distribution as normal. RESULTS: In the control group, the hemispheric activity index increased 1.1 times after treatment. In Group 2, following the dental status questionnaire, the index of hemispheric activity increased 1.3 times in males with a positive emotional mood (P ≤ 0.01). A 2.2-fold and 2.1-fold (P ≤ 0.01) increase was observed among female and male patients with a negative emotional mood in Group 2, respectively. After the treatment, the hemispheric activity index in Group 1 increased by 1.1 times for males with a positive mood (P ≤ 0.01) and by 1.2 times for male and female patients with a negative mood (P ≤ 0.05). Direct correlation was recorded between the increase in the number of scores and emotional mood among males and females from Group 1 (0.72 and 0.73, respectively). After the survey, a correlation was established between the values of the hemispheric activity index and the increase in scores among males (0.82) and females (0.81). There was also a connection between the increase in scores and the level of personal anxiety in both male (0.57) and female (0.66) patients, as well as between the increase in scores and the level of reactive anxiety (0.56 and 0.57, respectively). CONCLUSIONS: Changes in the hemispheric activity index were shown to be related to the patient's dental condition questionnaire. Besides, there is a relationship with the type of dental service. The practical application of this study implies that more reliable information about the patient's satisfaction with the quality of dental care provided can be obtained using not only standard psychodiagnostic methods but also questionnaires on the patient's dental status. Once the survey is completed and the data obtained analyzed, it is possible to define the correct strategy to restore the patient's physical and mental health after dental treatment.

Targeting Wee1 kinase as a therapeutic approach in Hematological Malignancies.

Hematologic malignancies include various diseases that develop from hematopoietic stem cells of bone marrow or lymphatic organs. Currently, conventional DNA-damage-based chemotherapy drugs are approved as standard therapeutic regimens for these malignancies. Although many improvements have been made, patients with relapsed or refractory hematological malignancies have a poor prognosis. Therefore, novel and practical therapeutic approaches are required for the treatment of these diseases. Interestingly several studies have shown that targeting Wee1 kinase in the Hematological malignancies, including AML, ALL, CML, CLL, DLBCL, BL, MCL, etc., can be an effective therapeutic strategy. It plays an essential role in regulating the cell cycle process by abrogating the G2-M cell-cycle checkpoint, which provides time for DNA damage repair before mitotic entry. Consistently, Wee1 overexpression is observed in various Hematological malignancies. Also, in healthy normal cells, repairing DNA damages occurs due to G1-S checkpoint function; however, in the cancer cells, which have an impaired G1-S checkpoint, the damaged DNA repair process depends on the G2-M checkpoint function. Thus, Wee1 inhibition could be a promising target in the presence of DNA damage in order to potentiate multiple therapeutic drugs. This review summarized the potentials and challenges of Wee1 inhibition combined with other therapies as a novel effective therapeutic strategy in Hematological malignancies.

CAR-engineered NK cells; a promising therapeutic option for treatment of hematological malignancies.

Adoptive cell therapy has received a great deal of interest in the treatment of advanced cancers that are resistant to traditional therapy. The tremendous success of chimeric antigen receptor (CAR)-engineered T (CAR-T) cells in the treatment of cancer, especially hematological cancers, has exposed CAR's potential. However, the toxicity and significant limitations of CAR-T cell immunotherapy prompted research into other immune cells as potential candidates for CAR engineering. NK cells are a major component of the innate immune system, especially for tumor immunosurveillance. They have a higher propensity for immunotherapy in hematologic malignancies because they can detect and eliminate cancerous cells more effectively. In comparison to CAR-T cells, CAR-NK cells can be prepared from allogeneic donors and are safer with a lower chance of cytokine release syndrome and graft-versus-host disease, as well as being a more efficient antitumor activity with high efficiency for off-the-shelf production. Moreover, CAR-NK cells may be modified to target various antigens while also increasing their expansion and survival in vivo. Extensive preclinical research has shown that NK cells can be effectively engineered to express CARs with substantial cytotoxic activity against both hematological and solid tumors, establishing evidence for potential clinical trials of CAR-NK cells. In this review, we discuss recent advances in CAR-NK cell engineering in a variety of hematological malignancies, as well as the main challenges that influence the outcomes of CAR-NK cell-based tumor immunotherapies.

A paradigm shift in cell-free approach: the emerging role of MSCs-derived exosomes in regenerative medicine.

Recently, mesenchymal stem/stromal cells (MSCs) due to their pro-angiogenic, anti-apoptotic, and immunoregulatory competencies along with fewer ethical issues are presented as a rational strategy for regenerative medicine. Current reports have signified that the pleiotropic effects of MSCs are not related to their differentiation potentials, but rather are exerted through the release of soluble paracrine molecules. Being nano-sized, non-toxic, biocompatible, barely immunogenic, and owning targeting capability and organotropism, exosomes are considered nanocarriers for their possible use in diagnosis and therapy. Exosomes convey functional molecules such as long non-coding RNAs (lncRNAs) and micro-RNAs (miRNAs), proteins (e.g., chemokine and cytokine), and lipids from MSCs to the target cells. They participate in intercellular interaction procedures and enable the repair of damaged or diseased tissues and organs. Findings have evidenced that exosomes alone are liable for the beneficial influences of MSCs in a myriad of experimental models, suggesting that MSC- exosomes can be utilized to establish a novel cell-free therapeutic strategy for the treatment of varied human disorders, encompassing myocardial infarction (MI), CNS-related disorders, musculoskeletal disorders (e.g. arthritis), kidney diseases, liver diseases, lung diseases, as well as cutaneous wounds. Importantly, compared with MSCs, MSC- exosomes serve more steady entities and reduced safety risks concerning the injection of live cells, such as microvasculature occlusion risk. In the current review, we will discuss the therapeutic potential of MSC- exosomes as an innovative approach in the context of regenerative medicine and highlight the recent knowledge on MSC- exosomes in translational medicine, focusing on in vivo researches.

CAR-NK cell in cancer immunotherapy; A promising frontier.

Chimeric antigen receptors (CARs) have a unique facet of synthetic biology and offer a paradigm shift in personalized medicine as they can use and redirect the patient's immune cells to attack cancer cells. CAR-natural killer (NK) cells combine the targeted specificity of antigens with the subsequent intracellular signaling ability of the receptors to increase their anti-cancer functions. Importantly, CAR-NK cells can be utilized as universal cell-based therapy without requiring human leukocyte antigen (HLA) matching or earlier contact with tumor-associated antigens (TAAs). Indeed, CAR-NK cells can be adapted to recognize various antigens, hold higher proliferation capacity, and in vivo persistence, show improved infiltration into the tumors, and the ability to overcome the resistant tumor microenvironment leading to sustained cytotoxicity against tumors. Accumulating evidence from recent in vivo studies rendering CAR-NK cell anti-cancer competencies renewed the attention in the context of cancer immunotherapy, as these redirected effector cells can be used in the development of the "off-the-shelf" anti-cancer immunotherapeutic products. In the current review, we focus on the therapeutic efficacy of CAR-NK cell therapies for treating various human malignancies, including hematological malignancies and solid tumors, and will discuss the recent findings in this regard, with a special focus on animal studies.

Chemokine CXCL14; a double-edged sword in cancer development.

Cancer is a leading cause of death worldwide and imposes a substantial financial burden. Therefore, it is essential to develop cost-effective approaches to inhibit tumor growth and development. The imbalance of cytokines and chemokines play an important role among different mechanisms involved in cancer development. One of the strongly conserved chemokines that is constitutively expressed in skin epithelia is the chemokine CXCL14. As a member of the CXC subfamily of chemokines, CXCL14 is responsible for the infiltration of immune cells, maturation of dendritic cells, upregulation of major histocompatibility complex (MHC)-I expression, and cell mobilization. Moreover, dysregulation of CXCL14 in several cancers has been identified by several studies. Depending on the type or origin of the tumor and components of the tumor microenvironment, CXCL14 plays a conflicting role in cancer. Although fibroblast-derived CXCL14 has a tumor-supportive role, epithelial-derived CXCL14 mainly inhibits tumor progression. Hence, this review will elucidate what is known on the mechanisms of CXCL14 and its therapeutic approaches in tumor treatment. CXCL14 is a promising approach for cancer immunotherapy.

The Most Competent Plant-Derived Natural Products for Targeting Apoptosis in Cancer Therapy.

Cancer is a challenging problem for the global health community, and its increasing burden necessitates seeking novel and alternative therapies. Most cancers share six basic characteristics known as "cancer hallmarks", including uncontrolled proliferation, refractoriness to proliferation blockers, escaping apoptosis, unlimited proliferation, enhanced angiogenesis, and metastatic spread. Apoptosis, as one of the best-known programmed cell death processes, is generally promoted through two signaling pathways, including the intrinsic and extrinsic cascades. These pathways comprise several components that their alterations can render an apoptosis-resistance phenotype to the cell. Therefore, targeting more than one molecule in apoptotic pathways can be a novel and efficient approach for both identifying new anticancer therapeutics and preventing resistance to therapy. The main purpose of this review is to summarize data showing that various plant extracts and plant-derived molecules can activate both intrinsic and extrinsic apoptosis pathways in human cancer cells, making them attractive candidates in cancer treatment.

Nanocurcumin improves Treg cell responses in patients with mild and severe SARS-CoV2.

In Coronavirus disease 2019 (COVID-19), a decreased number of regulatory T (Treg) cells and their mediated factors lead to a hyperinflammatory state due to overactivation of the inflammatory cells and factors during the infection. In the current study, we evaluated the Nanocurcumin effects on the Treg cell population and corresponding factors in mild and severe COVID-19 patients. To investigate the Nanocurcumin effects, 80 COVID-19 patients (40 at the severe stage and 40 at the mild stage) were selected and classified into Nanocurcumin and placebo arms. In both the Nanocurcumin and placebo groups, the Treg cell frequency, the gene expression of Treg transcription factor forkhead box P3 (FoxP3), and cytokines (IL-10, IL-35, and TGF-ß), as well as the serum levels of cytokines were measured before and after treatment. In both mild and severe COVID-19 patients, Nanocurcumin could considerably upregulate the frequency of Treg cells, the expression levels of FoxP3, IL-10, IL-35, and TGF-ß, as well as the serum secretion levels of cytokines in the Nanocurcumin-treated group compared to the placebo group. The abovementioned factors were remarkably increased in the post-treatment with Nanocurcumin before pre-treatment conditions. By contrast, it has been observed no notable alteration in the placebo group. Our findings revealed the SinaCurcumin® effective function in a significant increase in the number of Treg cells and their mediated factors in the Nanocurcumin group than in the placebo group in both mild and severe patients. Hence, it would be an efficient therapeutic agent in rehabilitating COVID-19 infected patients.

Any closer to successful therapy of multiple myeloma? CAR-T cell is a good reason for optimism.

Despite many recent advances on cancer novel therapies, researchers have yet a long way to cure cancer. They have to deal with tough challenges before they can reach success. Nonetheless, it seems that recently developed immunotherapy-based therapy approaches such as adoptive cell transfer (ACT) have emerged as a promising therapeutic strategy against various kinds of tumors even the cancers in the blood (liquid cancers). The hematological (liquid) cancers are hard to be targeted by usual cancer therapies, for they do not form localized solid tumors. Until recently, two types of ACTs have been developed and introduced; tumor-infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR)-T cells which the latter is the subject of our discussion. It is interesting about engineered CAR-T cells that they are genetically endowed with unique cancer-specific characteristics, so they can use the potency of the host immune system to fight against either solid or liquid cancers. Multiple myeloma (MM) or simply referred to as myeloma is a type of hematological malignancy that affects the plasma cells. The cancerous plasma cells produce immunoglobulins (antibodies) uncontrollably which consequently damage the tissues and organs and break the immune system function. Although the last few years have seen significant progressions in the treatment of MM, still a complete remission remains unconvincing. MM is a medically challenging and stubborn disease with a disappointingly low rate of survival rate. When comparing the three most occurring blood cancers (i.e., lymphoma, leukemia, and myeloma), myeloma has the lowest 5-year survival rate (around 40%). A low survival rate indicates a high mortality rate with difficulty in treatment. Therefore, novel CAR-T cell-based therapies or combination therapies along with CAT-T cells may bring new hope for multiple myeloma patients. CAR-T cell therapy has a high potential to improve the remission success rate in patients with MM. To date, many preclinical and clinical trial studies have been conducted to investigate the ability and capacity of CAR T cells in targeting the antigens on myeloma cells. Despite the problems and obstacles, CAR-T cell experiments in MM patients revealed a robust therapeutic potential. However, several factors might be considered during CAR-T cell therapy for better response and reduced side effects. Also, incorporating the CAT-T cell method into a combinational treatment schedule may be a promising approach. In this paper, with a greater emphasis on CAR-T cell application in the treatment of MM, we will discuss and introduce CAR-T cell's history and functions, their limitations, and the solutions to defeat the limitations and different types of modifications on CAR-T cells.

Mesenchymal stem cells and cancer therapy: insights into targeting the tumour vasculature.

A crosstalk established between tumor microenvironment and tumor cells leads to contribution or inhibition of tumor progression. Mesenchymal stem cells (MSCs) are critical cells that fundamentally participate in modulation of the tumor microenvironment, and have been reported to be able to regulate and determine the final destination of tumor cell. Conflicting functions have been attributed to the activity of MSCs in the tumor microenvironment; they can confer a tumorigenic or anti-tumor potential to the tumor cells. Nonetheless, MSCs have been associated with a potential to modulate the tumor microenvironment in favouring the suppression of cancer cells, and promising results have been reported from the preclinical as well as clinical studies. Among the favourable behaviours of MSCs, are releasing mediators (like exosomes) and their natural migrative potential to tumor sites, allowing efficient drug delivering and, thereby, efficient targeting of migrating tumor cells. Additionally, angiogenesis of tumor tissue has been characterized as a key feature of tumors for growth and metastasis. Upon introduction of first anti-angiogenic therapy by a monoclonal antibody, attentions have been drawn toward manipulation of angiogenesis as an attractive strategy for cancer therapy. After that, a wide effort has been put on improving the approaches for cancer therapy through interfering with tumor angiogenesis. In this article, we attempted to have an overview on recent findings with respect to promising potential of MSCs in cancer therapy and had emphasis on the implementing MSCs to improve them against the suppression of angiogenesis in tumor tissue, hence, impeding the tumor progression.

Outcomes after arthroscopic revision surgery for anterior cruciate ligament injuries.

Background and purpose - The frequency of primary anterior cruciate ligament (ACL) reconstruction is increasing resulting in more ACL revision surgeries. Therefore, we assessed survival rates of 2 different grafts for ACL revision surgery at 1- and 5-year follow-ups, as well as physical activity levels of patients after revision surgery.Patients and methods - This is a retrospective cohort study involving 218 patients (176 males) who had revision surgery for anterior cruciate ligament injuries between 2008 and 2017 at the Clinic of Traumatology, Orthopedics and Joint Pathology Clinic (I.M. Sechenov First Moscow State Medical University). A comparison group involved 189 patients with only primary surgery. Surgical interventions were performed according to the standard procedure using bone-patellar tendon-bone (BTB) and semitendinosus/gracilis (ST/G) autografts. The results of revision surgery were assessed at 1- and 5-year follow-ups by using the Lysholm and International Knee Documentation Committee scores.Results - Malpositioned bone tunnels were found in 87/218 patients (40%). At 1 and 5 years postoperatively, the revision BTB group had significantly better results in terms of IKDC and Lysholm scores than the revision ST/G group (p = 0.03, Mann-Whitney U-test), and these results were comparable to those in the comparison group. Graft survival after revision was lower than after the primary operation. However, the survival rate of 80% is quite high and is consistent with previous findings. There were no statistically reliable differences in survival between ST/G and BTB autografts.Interpretation - The graft choice for revision ACL surgery should be decided upon before surgery based on, among other things, the state of bone tunnels, in particular their position and degree of bone resorption. Tunnel widening that exceeds 14 mm (osteolysis) would require 2-stage surgery using a BTB autograft with bone plugs because it is larger than the ST/G autograft.

CAR T cells in solid tumors: challenges and opportunities.

BACKGROUND: CARs are simulated receptors containing an extracellular single-chain variable fragment (scFv), a transmembrane domain, as well as an intracellular region of immunoreceptor tyrosine-based activation motifs (ITAMs) in association with a co-stimulatory signal. MAIN BODY: Chimeric antigen receptor (CAR) T cells are genetically engineered T cells to express a receptor for the recognition of the particular surface marker that has given rise to advances in the treatment of blood disorders. The CAR T cells obtain supra-physiological properties and conduct as "living drugs" presenting both immediate and steady effects after expression in T cells surface. But, their efficacy in solid tumor treatment has not yet been supported. The pivotal challenges in the field of solid tumor CAR T cell therapy can be summarized in three major parts: recognition, trafficking, and surviving in the tumor. On the other hand, the immunosuppressive tumor microenvironment (TME) interferes with T cell activity in terms of differentiation and exhaustion, and as a result of the combined use of CARs and checkpoint blockade, as well as the suppression of other inhibitor factors in the microenvironment, very promising results were obtained from the reduction of T cell exhaustion. CONCLUSION: Nowadays, identifying and defeating the mechanisms associated with CAR T cell dysfunction is crucial to establish CAR T cells that can proliferate and lyse tumor cells severely. In this review, we discuss the CAR signaling and efficacy T in solid tumors and evaluate the most significant barriers in this process and describe the most novel therapeutic methods aiming to the acquirement of the promising therapeutic outcome in non-hematologic malignancies.

The role of non-coding genome in the behavior of infiltrated myeloid-derived suppressor cells in tumor microenvironment; a perspective and state-of-the-art in cancer targeted therapy.

Cancer is one of the healthcare problems that affect many communities around the world. Many factors contribute to cancer development. Besides, these factors are counted as the main impediment in cancer immunotherapy. Myeloid-derived suppressor cells (MDSCs) are one of these impediments. MDSCs inhibit the immune responses through various mechanisms such as inhibitory cytokine release and nitric oxide metabolite production. Several factors are involved in forming these cells, including tumor secreted cytokine and chemokines, transcription factors, and non-coding RNA. In the meantime, micro-RNAs (miRNAs) and long non-coding RNAs (lncRNAs) are the vital gene regulatory elements that affect gene expression. In this study, we are going to discuss the role of miRNAs and lncRNAs in MDSCs development in a cancer situation. It is hoped that miRNA and lncRNAs targeting may prevent the growth and development of these inhibitory cells in the cancer environment.