Circulating miRNA and circulating tumor DNA application as liquid biopsy markers in gastric cancer.

Liquid biopsy has been investigated as a novel method to overcome the numerous challenges in gastric cancer (GC) management. This non-invasive, feasible, and easy-to-repeat method has been shown to be cost-effective and capable of increasing diagnostic sensitivity and prognostic assessment. Additionally, it is potentially accurate to aid decision-making and personalized treatment planning. MicroRNA (miRNA) and circulating tumor DNA (ctDNA) markers can enhance GC management in various aspects, including diagnosis (mainly earlier diagnosis and the ability to perform population-based screening), prognosis (more precise stratification of prognosis), and treatment (including more accurate prediction of treatment response and earlier detection of resistance to the treatment). Concerning the treatment-related application, miRNAs' mimics and antagonists (by using two main strategies of restoring tumor suppressor miRNAs and inhibiting oncogene miRNAs) have been shown to be effective therapeutic agents. However, these need to be further validated in clinical trials. Furthermore, novel delivery systems, such as lipid-based vectors, polymeric-based vectors, and exosome-based delivery, have been developed to enhance the performance of these agents. Moreover, this paper explores the current detection and measuring methods for these markers. These approaches are categorized into direct methods (e.g., Chem-NAT, HTG EdgeSeq, and Multiplex Circulating Fireplex) and indirect methods (e.g., Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), qPCR, microarray, and NGS) for miRNA detection. For ctDNA measurement, main core technologies like NGS, digital PCR, real-time PCR, and mass spectrometry are suggested.

The multifaceted role of extracellular vesicles (EVs) in colorectal cancer: metastasis, immune suppression, therapy resistance, and autophagy crosstalk.

Extracellular vesicles (EVs) are lipid bilayer structures released by all cells and widely distributed in all biological fluids. EVs are implicated in diverse physiopathological processes by orchestrating cell-cell communication. Colorectal cancer (CRC) is one of the most common cancers worldwide, with metastasis being the leading cause of mortality in CRC patients. EVs contribute significantly to the advancement and spread of CRC by transferring their cargo, which includes lipids, proteins, RNAs, and DNAs, to neighboring or distant cells. Besides, they can serve as non-invasive diagnostic and prognostic biomarkers for early detection of CRC or be harnessed as effective carriers for delivering therapeutic agents. Autophagy is an essential cellular process that serves to remove damaged proteins and organelles by lysosomal degradation to maintain cellular homeostasis. Autophagy and EV release are coordinately activated in tumor cells and share common factors and regulatory mechanisms. Although the significance of autophagy and EVs in cancer is well established, the exact mechanism of their interplay in tumor development is obscure. This review focuses on examining the specific functions of EVs in various aspects of CRC, including progression, metastasis, immune regulation, and therapy resistance. Further, we overview emerging discoveries relevant to autophagy and EVs crosstalk in CRC.

A viral attack on brain tumors: the potential of oncolytic virus therapy.

Managing malignant brain tumors remains a significant therapeutic hurdle that necessitates further research to comprehend their treatment potential fully. Oncolytic viruses (OVs) offer many opportunities for predicting and combating tumors through several mechanisms, with both preclinical and clinical studies demonstrating potential. OV therapy has emerged as a potent and effective method with a dual mechanism. Developing innovative and effective strategies for virus transduction, coupled with immune checkpoint inhibitors or chemotherapy drugs, strengthens this new technique. Furthermore, the discovery and creation of new OVs that can seamlessly integrate gene therapy strategies, such as cytotoxic, anti-angiogenic, and immunostimulatory, are promising advancements. This review presents an overview of the latest advancements in OVs transduction for brain cancer, focusing on the safety and effectiveness of G207, G47Δ, M032, rQNestin34.5v.2, C134, DNX-2401, Ad-TD-nsIL12, NSC-CRAd-S-p7, TG6002, and PVSRIPO. These are evaluated in both preclinical and clinical models of various brain tumors.

The role of extracellular vesicles in immune cell exhaustion and resistance to immunotherapy.

INTRODUCTION: Extracellular vesicles (EVs) are membrane-bound nanoparticles for intercellular communication. Subtypes of EVs, namely exosomes and microvesicles transfer diverse, bioactive cargo to their target cells and eventually interfere with immune responses. Despite being a promising approach, cancer immunotherapy currently faces several challenges including immune resistance. EVs secreted from various sources in the tumor microenvironment provoke immune cell exhaustion and lower the efficacy of immunological treatments, such as CAR T cells and immune checkpoint inhibitors. AREAS COVERED: This article goes through the mechanisms of action of various types of EVs in inhibiting immune response and immunotherapies, and provides a comprehensive review of EV-based treatments. EXPERT OPINION: By making use of the distinctive features of EVs, natural or modified EVs are innovatively utilized as novel cancer therapeutics. They are occasionally coupled with currently established treatments to overcome their inadequacies. Investigating the properties and interactions of EVs and EV-based treatments is crucial for determining future steps in cancer therapeutics.

Role of long non-coding RNAs in cholangiocarcinoma: A systematic review and meta-analysis.

BACKGROUND: Cholangiocarcinoma (CCA), as a rare malignancy of the biliary tree, has a poor prognosis most of the time. CCA is highly epigenetically regulated and several long non-coding RNAs (lncRNA) have been investigated to have a diagnostic and prognostic role in CCA. The current study aimed to assess the studies finding relevant lncRNAs in CCA systematically. METHODS: International databases, including PubMed, Cochrane Library, and Embase, were comprehensively searched in order to identify studies investigating any lncRNA in CCA. After screening by title/abstract and full-text, necessary data were extracted. Random-effect meta-analysis was performed for pooling the areas under the curve (AUCs), specificity, and sensitivity of lncRNAs for the diagnosis of CCA. RESULTS: A total of 33 studies were chosen to be included in the final analysis, comprised of 2677 patients. Meta-analysis of AUCs for evaluation of CCA resulted in pooled AUC of 0.79 (95% CI: 0.75-0.82; I2 = 69.11, p < .01). Additionally, overall sensitivity of 0.80 (95% CI 0.75-0.84) and specificity of 0.77 (95% CI: 0.68-0.84) were observed. Measurement of lncRANs in the assessment of CCA also improved overall survival significantly (effect size 1.61, 95% CI: 1.39-1.82). A similar result was found for progression-free survival (effect size 1.57, 95% CI: 1.20-1.93). CONCLUSION: Based on our findings, lncRNAs showed promising results as biomarkers in the diagnosis of CCA since they had acceptable sensitivity and specificity, in addition to the fact that improved survival in this poor prognosis cancer. Further studies might be needed to address this issue and find the best clinically useful lncRNA.

Biologic Therapy in Pediatric Chronic Rhinosinusitis: A Systematic Review.

OBJECTIVE: Provide clinicians with current evidence for biologic therapy in children with chronic rhinosinusitis with nasal polyposis (CRSwNP). DATA SOURCES: PubMed, MEDLINE, Cochrane, and clinical trial registries. REVIEW METHODS: Key search terms related to biologic therapy in pediatric CRSwNP were identified via a structured query of current medical literature and clinical trial databases. CONCLUSIONS: There is a dearth of active clinical trials and research studies for biologics targeting pediatric CRSwNP. There is an ongoing compassionate-use clinical trial involving Dupilumab for children with nasal polyps as well as only 1 published work specifically focused on Dupilumab for pediatric CRSwNP in the setting of aspirin-exacerbated respiratory disease. IMPLICATIONS FOR PRACTICE: For children with atopic dermatitis, asthma, and chronic idiopathic urticaria, biologic therapies such as Omalizumab, Dupilumab, and Mepolizumab have gained Food and Drug Administration approval. The role of biologic therapy in pediatric CRSwNP demonstrates significant promise in the comprehensive management of the unified airway. Additional Phase III trials are necessary to broaden clinical indications for children with comorbid conditions and complex sinonasal disease.

The role of long noncoding RNAs in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with a poor prognosis leading to death. The diagnosis and treatment of ALS are inherently challenging due to its complex pathomechanism. Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides involved in different cellular processes, incisively gene expression. In recent years, more studies have been conducted on lncRNA classes and interference in different disease pathologies, showing their promising contribution to diagnosing and treating neurodegenerative diseases. In this review, we discussed the role of lncRNAs like NEAT1 and C9orf72-as in ALS pathogenesis mechanisms caused by mutations in different genes, including TAR DNA-binding protein-43 (TDP-43), fused in sarcoma (FUS), superoxide dismutase type 1 (SOD1). NEAT1 is a well-established lncRNA in ALS pathogenesis; hence, we elaborate on its involvement in forming paraspeckles, stress response, inflammatory response, and apoptosis. Furthermore, antisense lncRNAs (as-lncRNAs), a key group of transcripts from the opposite strand of genes, including ZEB1-AS1 and ATXN2-AS, are discussed as newly identified components in the pathology of ALS. Ultimately, we review the current standing of using lncRNAs as biomarkers and therapeutic agents and the future vision of further studies on lncRNA applications.

Biomimetic nanotechnology for cancer immunotherapy: State of the art and future perspective.

Cancer continues to be a significant worldwide cause of mortality. This underscores the urgent need for novel strategies to complement and overcome the limitations of conventional therapies, such as imprecise targeting and drug resistance. Cancer Immunotherapy utilizes the body's immune system to target malignant cells, reducing harm to healthy tissue. Nevertheless, the efficacy of immunotherapy exhibits variation across individuals and has the potential to induce autoimmune responses. Biomimetic nanoparticles (bNPs) have transformative potential in cancer immunotherapy, promising improved accurate targeting, immune system activation, and resistance mechanisms, while also reducing the occurrence of systemic autoimmune side effects. This integration offers opportunities for personalized medicine and better therapeutic outcomes. Despite considerable potential, bNPs face barriers like insufficient targeting, restricted biological stability, and interactions within the tumor microenvironment. The resolution of these concerns is crucial in order to expedite the integration of bNPs from the research setting into clinical therapeutic uses. In addition, optimizing manufacturing processes and reducing bNP-related costs are essential for practical implementation. The present research introduces comprehensive classifications of bNPs as well as recent achievements in their application in cancer immunotherapies, emphasizing the need to address barriers for swift clinical integration.

Inflammation and oxidative stress in epileptic children: from molecular mechanisms to clinical application of ketogenic diet.

Childhood epilepsy affects up to 1 % of children. It has been shown that 30 % of patients are resistant to drug treatments, making further investigation of other potential treatment strategies necessary. One such approach is the ketogenic diet (KD) showing promising results and potential benefits beyond the use of current antiepileptic drugs. This study aims to investigate the effects of KD on inflammation and oxidative stress, as one of the main suggested mechanisms of neuroprotection, in children with epilepsy. This narrative review was conducted using the Medline and Google Scholar databases, and by searching epilepsy, drug-resistant epilepsy, child, children, ketogenic, ketogenic diet, diet, ketogenic, keto, ketone bodies (BHB), PUFA, gut microbiota, inflammation, inflammation mediators, neurogenic inflammation, neuroinflammation, inflammatory marker, adenosine modulation, mitochondrial function, MTOR pathway, Nrf2 pathway, mitochondrial dysfunction, PPARÉ£, oxidative stress, ROS/RNS, and stress oxidative as keywords. Compelling evidence underscores inflammation and oxidative stress as pivotal factors in epilepsy, even in cases with genetic origins. The ketogenic diet effectively addresses these factors by reducing ROS and RNS, enhancing antioxidant defenses, improving mitochondrial function, and regulating inflammatory genes. Additionally, KD curbs pro-inflammatory cytokine and chemokine production by dampening NF-κB activation, inhibiting the NLRP3 inflammasome, increasing brain adenosine levels, mTOR pathway inhibition, upregulating PPARÉ£ expression, and promoting a healthy gut microbiota while emphasizing the consumption of healthy fats. KD could be considered a promising therapeutic intervention in patients with epilepsy particularly in drug-resistant epilepsy cases, due to its targeted approach addressing oxidative stress and inflammatory mechanisms.

The progressive trend of modeling and drug screening systems of breast cancer bone metastasis.

Bone metastasis is considered as a considerable challenge for breast cancer patients. Various in vitro and in vivo models have been developed to examine this occurrence. In vitro models are employed to simulate the intricate tumor microenvironment, investigate the interplay between cells and their adjacent microenvironment, and evaluate the effectiveness of therapeutic interventions for tumors. The endeavor to replicate the latency period of bone metastasis in animal models has presented a challenge, primarily due to the necessity of primary tumor removal and the presence of multiple potential metastatic sites.The utilization of novel bone metastasis models, including three-dimensional (3D) models, has been proposed as a promising approach to overcome the constraints associated with conventional 2D and animal models. However, existing 3D models are limited by various factors, such as irregular cellular proliferation, autofluorescence, and changes in genetic and epigenetic expression. The imperative for the advancement of future applications of 3D models lies in their standardization and automation. The utilization of artificial intelligence exhibits the capability to predict cellular behavior through the examination of substrate materials' chemical composition, geometry, and mechanical performance. The implementation of these algorithms possesses the capability to predict the progression and proliferation of cancer. This paper reviewed the mechanisms of bone metastasis following primary breast cancer. Current models of breast cancer bone metastasis, along with their challenges, as well as the future perspectives of using these models for translational drug development, were discussed.

Long non-coding RNA as a potential diagnostic and prognostic biomarker in melanoma: A systematic review and meta-analysis.

Recently, long noncoding RNAs (lncRNAs) have been applied as biomarkers for melanoma patients. In this systematic review and meta-analysis, we investigated the diagnostic and prognostic value of lncRNAs. We used the keywords 'lncRNA' and 'melanoma' to search databases for studies published before June 14th, 2023. The specificity, sensitivity and AUC were utilized to assess diagnostic accuracy and the prognostic value was assessed using overall survival, progression-free survival and disease-free survival hazard ratios. After screening 1191 articles, we included seven studies in the diagnostic evaluation section and 17 studies in the prognosis evaluation section. The Reitsma bivariate model estimated a cumulative sensitivity of 0.724 (95% CI: 0.659-0.781, p < 0.001) and specificity of 0.812 (95% CI: 0.752-0.859, p < 0.001). The pooled AUC was 0.780 (95% CI: 0.749-0.811, p < 0.0001). The HR for overall survival was 2.723 (95% CI: 2.259-3.283, p < 0.0001). Two studies reported an HR for overall survival less than one, with an HR of 0.348 (95% CI: 0.200-0.607, p < 0.0002). The HR for progression-free survival was 2.913 (95% CI: 2.050-4.138, p < 0.0001). Four studies reported an HR less than one, with an HR of 0.457 (95% CI: 0.256-0.817). The HR for disease-free survival was 2.760 (95% CI: 2.009-3.792, p < 0.0001). In conclusion, the expression of lncRNAs in melanoma patients affects survival and prognosis. LncRNAs can also be employed as diagnostic biomarkers.

Clinical heterogeneity in families with multiple cases of inborn errors of immunity.

BACKGROUND: Inborn errors of immunity (IEI) are a diverse range of genetic immune system illnesses affecting the innate and/or adaptive immune systems. Variable expressivity and incomplete penetrance have been reported in IEI patients with similar clinical diagnoses or even the same genetic mutation. METHODS: Among all recorded patients in the national IEI registry, 193 families with multiple cases have been recognized. Clinical, laboratory and genetic variability were compared between 451 patients with different IEI entities. RESULTS: The diagnosis of the first children led to the earlier diagnosis, lower diagnostic delay, timely treatment and improved survival in the second children in the majority of IEI. The highest discordance in familial lymphoproliferation, autoimmunity and malignancy were respectively observed in STK4 deficiency, DNMT3B deficiency and ATM deficiency. Regarding immunological heterogeneity within a unique family with multiple cases of IEI, the highest discordance in CD3+, CD4+, CD19+, IgM and IgA levels was observed in syndromic combined immunodeficiencies (CID), while non-syndromic CID particularly severe combined immunodeficiency (SCID) manifested the highest discordance in IgG levels. Identification of the first ATM-deficient patient can lead to improved care and better survival in the next IEI children from the same family. CONCLUSION: Intrafamilial heterogeneity in immunological and/or clinical features could be observed in families with multiple cases of IEI indicating the indisputable role of appropriate treatment and preventive environmental factors besides specific gene mutations in the variable observed penetrance or expressivity of the disease. This also emphasizes the importance of implementing genetic evaluation in all members of a family with a history of IEI even if there is no suspicion of an underlying IEI as other factors besides the underlying genetic defects might cause a milder phenotype or delay in presentation of clinical features. Thus, affected patients could be timely diagnosed and treated, and their quality of life and survival would improve.

Stem Cell-Based Regenerative Approaches for the Treatment of Cleft Lip and Palate: A Comprehensive Review.

Cleft lip and/or palate (CLP) is a prevalent congenital craniofacial abnormality that can lead to difficulties in eating, speaking, hearing, and psychological distress. The traditional approach for treating CLP involves bone graft surgery, which has limitations, post-surgical complications, and donor site morbidity. However, regenerative medicine has emerged as a promising alternative, employing a combination of stem cells, growth factors, and scaffolds to promote tissue regeneration. This review aims to provide a comprehensive overview of stem cell-based regenerative approaches in the management of CLP. A thorough search was conducted in the Medline/PubMed and Scopus databases, including cohort studies, randomized controlled trials, case series, case controls, case reports, and animal studies. The identified studies were categorized into two main groups: clinical studies involving human subjects and in vivo studies using animal models. While there are only a limited number of studies investigating the combined use of stem cells and scaffolds for CLP treatment, they have shown promising results. Various types of stem cells have been utilized in conjunction with scaffolds. Importantly, regenerative methods have been successfully applied to patients across a broad range of age groups. The collective findings derived from the reviewed studies consistently support the notion that regenerative medicine holds potential advantages over conventional bone grafting and represents a promising therapeutic option for CLP. However, future well-designed clinical trials, encompassing diverse combinations of stem cells and scaffolds, are warranted to establish the clinical efficacy of these interventions with a larger number of patients.

Mesenchymal stromal cells and CAR-T cells in regenerative medicine: The homing procedure and their effective parameters.

Mesenchymal stromal cells (MSCs) and chimeric antigen receptor (CAR)-T cells are two core elements in cell therapy procedures. MSCs have significant immunomodulatory effects that alleviate inflammation in the tissue regeneration process, while administration of specific chemokines and adhesive molecules would primarily facilitate CAR-T cell trafficking into solid tumors. Multiple parameters affect cell homing, including the recipient's age, the number of cell passages, proper cell culture, and the delivery method. In addition, several chemokines are involved in the tumor microenvironment, affecting the homing procedure. This review discusses parameters that improve the efficiency of cell homing and significant cell therapy challenges. Emerging comprehensive mechanistic strategies such as non-systemic and systemic homing that revealed a significant role in cell therapy remodeling were also reviewed. Finally, the primary implications for the development of combination therapies that incorporate both MSCs and CAR-T cells for cancer treatment were discussed.

Nephrectomy and IVC thrombectomy in renal cancer: a narrative review.

Renal cell carcinoma accounts for two to three percent of adult malignancies and can lead to inferior vena cava (IVC) thrombosis. This condition can decrease the rate of 5-year survival for patients to 60%. The treatment of choice in such cases is radical nephrectomy and inferior vena cava thrombectomy. This surgery is one of the most challenging due to many perioperative complications. There are many controversial methods reported in the literature. Achieving the free of tumor IVC wall and the possibility of thrombectomy in cases of level III and level IV IVC thrombosis are two essential matters previously advocated open approaches. Nevertheless, open approaches are being replaced by minimally invasive techniques despite the difficulty of the surgical management of IVC thrombectomy. This paper aims to review recent evidence about new surgical methods and a comparison of open, laparoscopic, and robotic approaches. In this review, we present the latest surgical strategies for IVC thrombectomy and compare open and minimally invasive approaches to achieve the optimal surgical technique. Due to the different anatomy of the left and right kidneys and variable extension of venous thrombosis, we investigate surgical methods for left and right kidney cancer and each level of IVC venous thrombosis separately.

The Reconstitution of T-cells after Allogeneic Hematopoietic Stem Cell Transplant in a Pediatric Patient with Congenital Amegakaryocytic Thrombocytopenia (CAMT).

BACKGROUND: Congenital amegakaryocytic thrombocytopenia (CAMT) is a bone marrow failure syndrome with autosomal recessive inheritance characterized by the lack of megakaryocytes and thrombocytopenia. The cause of the disease is a mutation in the c-Mpl gene, which encodes the thrombopoietin (TPO) receptor. The main treatment for this genetic disorder is an allogeneic hematopoietic stem cell transplant (allo-HSCT). However, transplant-related mortality, development of acute and chronic graft-versushost disease (GvHD), and susceptibility to opportunistic infections are major barriers to transplantation. Delay in the reconstitution of T cells and imbalance in the regeneration of distinct functional CD4 and CD8 T-cell subsets mainly affect post-transplant complications. We report a case of CAMT, who developed acute GvHD but had no signs and symptoms of chronic GvHD following allo-HSCT. CASE PRESENTATION: At the age of four, she presented with petechiae and purpura. In laboratory investigations, pancytopenia without organomegaly, and cellularity less than 5% in bone marrow biopsy, were observed. A primary diagnosis of idiopathic aplastic anemia was made, and she was treated with prednisolone, cyclosporine, and anti-thymocyte globulin (ATG), which did not respond. Genetic analysis revealed the mutation c.1481T>G (p. L494W) in exon 10 of the c-Mpl gene, and the diagnosis of CAMT was confirmed. The patient underwent allo-HSCT from a healthy sibling donor. Alloimmunization reactions and immune disorders were present due to long-term treatment with immunosuppressive medications and repeated blood and platelet transfusions. Hence, the regeneration of T-lymphocytes after allo-HSCT was evaluated. CONCLUSION: Successful treatment of acute GvHD prevented advancing the condition to chronic GvHD, and this was accompanied by delayed T-cell reconstitution through an increase in Treg:Tcons ratio.

Self-assembled peptide/polymer hybrid nanoplatform for cancer immunostimulating therapies.

Integrating peptide epitopes in self-assembling materials is a successful strategy to obtain nanovaccines with high antigen density and improved efficacy. In this study, self-assembling peptides containing MAGE-A3/PADRE epitopes were designed to generate functional therapeutic nanovaccines. To achieve higher stability, peptide/polymer hybrid nanoparticles were formulated by controlled self-assembly of the engineered peptides. The nanoparticles showed good biocompatibility to both human red blood- and dendritic cells. Incubation of the nanoparticles with immature dendritic cells triggered immune effects that ultimately activated CD8 + cells. The antigen-specific and IgG antibody responses of healthy C57BL/6 mice vaccinated with the nanoparticles were analyzed. The in vivo results indicate a specific response to the nanovaccines, mainly mediated through a cellular pathway. This research indicates that the immunogenicity of peptide epitope vaccines can be effectively enhanced by developing self-assembled peptide-polymer hybrid nanostructures.

Immune checkpoint inhibitors therapy as the game-changing approach for pediatric lymphoma: A brief landscape.

Lymphoma is known as the third most common malignancy in children, and its prevalence and mortality are increasing. Common treatments, including chemotherapy, radiotherapy, and also surgery, despite their efficacy, have many side effects and, have a high chance of disease relapse. Immune Checkpoint Inhibitors (ICIs) offer a promising alternative with potentially fewer risks of relapse and toxicity. This review article aims to investigate the efficacy and safety of ICIs, either as monotherapy or in combination, for pediatric lymphoma patients. ICIs have revolutionized cancer treatment in recent years and have shown remarkable results in several adult cancers. However, their efficacy in treating pediatrics requires further investigation. Nevertheless, some ICIs, including nivolumab, pembrolizumab, and ipilimumab, have demonstrated encouraging outcomes. ICIs therapy is not without risks and can cause side effects, including rash, itching, vitiligo, abdominal pain, diarrhea, dysphagia, epigastric pain, nausea, vomiting, thyroid, and pituitary dysfunction. Overall, this review article highlights the potential benefits and risks of ICIs in treating pediatric lymphoma.

Radiotherapy Combination: Insight from Tumor Immune Microenvironment (TIME).

The view of Radiotherapy (RT) as a simple inducer of DNA damage resulting in tumor cell death has dramatically changed in recent years, and it is now widely accepted that RT can trigger an immune response which provides a sound basis for combining RT with immunotherapy. Given that, radiation can be delivered with different regimens, its effect on immune responses and Tumor Immune Microenvironment (TIME) may vary with dose and fractionation schedule. This fractional dose dependency may need to be more considered because of recent developments in RT delivery techniques making it possible to deliver precisely higher dosages per fraction (hypofractionation) while reducing exposure to normal tissues. Although combining radiotherapy with immunotherapy could be a promising strategy for synergistic enhancement of treatment efficacy, the selection of the best-matched combination of immunotherapy with each radiotherapy scheme remains to be addressed. Thus, for designing better therapeutic combinations, it is necessary to understand the immunological effects of RT. Here, we review the impact of conventional and different hypofractionation radiation schedules on the TIME. Subsequently, we highlight how knowing about these interactions may have implications for choosing a rational combination with targeted therapies.

Brain-derived neurotrophic factor in fibromyalgia: A systematic review and meta-analysis of its role as a potential biomarker.

BACKGROUND: Fibromyalgia (FM) is a form of chronic pain disorder accompanied by several tender points, fatigue, sleeping and mood disturbances, cognitive dysfunction, and memory problems. Brain-derived neurotrophic factor (BDNF) is also a mediator of neurotrophin for many activity-dependent processes in the brain. Despite numerous research studies investigating BDNF in FM, contradictory results have been reported. Thus, we investigated the overall effect shown by studies to find the association between peripheral BDNF concentrations and its gene polymorphisms with FM. METHODS: A systematic search in online international databases, including PubMed, Cochrane Library, Embase, the Web of Science, and Scopus was performed. Relevant studies assessing BDNF levels or gene polymorphism in patients with FM and comparing them with controls were included. Case reports, reviews, and non-English studies were excluded. We conducted the random-effect meta-analysis to estimate the pooled standardized mean difference (SMD) or odds ratio (OR) and 95% confidence interval (CI). RESULTS: Twenty studies were found to be included composed of 1,206 FM patients and 1,027 controls. The meta-analysis of 15 studies indicated that the circulating BDNF levels were significantly higher in FM (SMD 0.72, 95% CI 0.12 to 1.31; p-value = 0.02). However, no difference between the rate of Val/Met carrier status at the rs6265 site was found (p-value = 0.43). Using meta-regression, the sample size and age variables accounted for 4.69% and 6.90% of the observed heterogeneity of BDNF level analysis, respectively. CONCLUSION: Our meta-analysis demonstrated that FM is correlated with increased peripheral BDNF levels. This biomarker's diagnostic and prognostic value should be further investigated in future studies.