-
Cancer Medicine Dec 2020The prognostic and clinicopathological significance of POU Class 5 Homeobox 1 (POU5F1) among various cancers are disputable heretofore. The diagnostic value and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The prognostic and clinicopathological significance of POU Class 5 Homeobox 1 (POU5F1) among various cancers are disputable heretofore. The diagnostic value and functional mechanism of POU5F1 in liver hepatocellular carcinoma (LIHC) have not been studied thoroughly.
METHODS
An integrative strategy of meta-analysis, bioinformatics, and wet-lab approach was used to explore the diagnostic and prognostic significance of POU5F1 in various types of tumors, especially in LIHC. Meta-analysis was utilized to investigate the impact of POU5F1 on prognosis and clinicopathological parameters in various cancers. The expression level and diagnostic value of POU5F1 were assessed by qPCR in plasma collected from LIHC patients and controls. The correlation between POU5F1 and tumor infiltrating immune cells (TIICs) in LIHC was evaluated by CIBERSORT. Gene set enrichment analysis (GSEA) was performed based on TCGA. Hub genes and related pathways were identified on the basis of co-expression genes of POU5F1.
RESULTS
Elevated POU5F1 was associated with poor OS, DFS, RFS, and DSS in various cancers. POU5F1 was confirmed as an independent risk factor for LIHC and correlated with tumor occurrence, stage, and invasion depth. The combination of POU5F1 and AFP in plasma was with high diagnostic validity (AUC = 0.902, p < .001). Specifically, the level of POU5F1 was correlated with infiltrating levels of B cells, T cells, dendritic cells, and monocytes in LIHC. GSEA indicated that POU5F1 participated in multiple cancer-related pathways and cell proliferation pathways. Moreover, CBX3, CCHCR1, and NFYC were filtered as the central hub genes of POU5F1.
CONCLUSION
Our study identified POU5F1 as a pan-cancer gene that could not only be a prognostic and diagnostic biomarker in various cancers, especially in LIHC, but functionally carcinogenic in LIHC.
Topics: Algorithms; Biomarkers, Tumor; Carcinoma, Hepatocellular; Case-Control Studies; Computational Biology; Databases, Genetic; Disease Progression; Disease-Free Survival; Female; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Humans; Liver Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Octamer Transcription Factor-3; Predictive Value of Tests; Protein Interaction Maps; Reverse Transcriptase Polymerase Chain Reaction; Risk Assessment; Risk Factors; Time Factors
PubMed: 32978904
DOI: 10.1002/cam4.3486 -
Medicine Apr 2021This meta-analysis was designed to systematically evaluate whether autologous cytokine-induced killer cells (CIK) or dendritic cells and cytokine-induced killer cells... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This meta-analysis was designed to systematically evaluate whether autologous cytokine-induced killer cells (CIK) or dendritic cells and cytokine-induced killer cells (DC-CIK) immunotherapy combined with chemotherapy can improve the therapeutic effect and safety of chemotherapy in esophageal cancer (EC).
MATERIALS AND METHODS
Randomized controlled trials (RCTs) were electronically searched databases including CNKI, WanFang, WeiPu, CBMDisc, PubMed, Web of Science, EMbase, the Cochrane Library, and Clinical Trials. The databases were searched for articles published until June 2019. Two researchers independently screened the literature, extracted data, and evaluated the quality of the included literature. Meta-analysis was performed using RevMan5.3.
RESULTS
Seventeen studies (1416 participants) were included. The differences between CIK/DC-CIK combination chemotherapy and chemotherapy alone were significant. The results displayed that the number of CD3+, CD4+, CD4+/CD8+, and NK cells was significantly increased after 1 to 2 weeks of treatment with CIK/DC-CIK cells in the treatment group (all P < .05). In addition, the results shown that 1-year overall survival was significantly prolonged (P < .0001) and quality of life was improved (P = .001) in EC chemotherapy combined with immunotherapy groups compared with conventional treatment. Furthermore, cytokine expression levels of interleukin 2 (IL-2), tumor necrosis factor α (TNF-α), and interleukin 12 (IL-12) were significantly increased (P = .0003) as well as the levels of immunoglobulins were elevated (P < .00001). Serum levels of tumor marker molecules, carcinoembryonic antigen (CEA), carbohydrate antigen (CA)-199, and CA-125 were lower in treatment groups than that of control groups (P < .00001). No fatal adverse reactions were noted (P = .04).
CONCLUSIONS
It is safe and effective for patients to use chemotherapy combined with CIK/DC-CIK immunotherapy. Immunotherapy can simultaneously improve the antitumor immune response. Specifically, DC-CIK cells can increase T lymphocyte subsets, CIK cells, NK cells, and immunoglobulins in peripheral blood to enhance antitumor immunity. Therefore, combination therapy enhances the immune function and improves the therapeutic efficacy of patients with EC.
Topics: Adaptive Immunity; Aged; Antineoplastic Agents; Combined Modality Therapy; Cytokine-Induced Killer Cells; Dendritic Cells; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 33787569
DOI: 10.1097/MD.0000000000024519 -
Cancers May 2022Bladder cancer is the ninth most common cancer worldwide. Over 75% of non-muscle invasive cancer patients require conservative local treatment, while the remaining 25%... (Review)
Review
Bladder cancer is the ninth most common cancer worldwide. Over 75% of non-muscle invasive cancer patients require conservative local treatment, while the remaining 25% of patients undergo radical cystectomy or radiotherapy. Immune checkpoint inhibitors represent a novel class of immunotherapy drugs that restore natural antitumoral immune activity via the blockage of inhibitory receptors and ligands expressed on antigen-presenting cells, T lymphocytes and tumour cells. The use of immune checkpoint inhibitors in bladder cancer has been expanded from the neoadjuvant setting, i.e., after radical cystectomy, to the adjuvant setting, i.e., before the operative time or chemotherapy, in order to improve the overall survival and to reduce the morbidity and mortality of both the disease and its treatment. However, some patients do not respond to checkpoint inhibitors. As result, the capability for identifying patients that are eligible for this immunotherapy represent one of the efforts of ongoing studies. The aim of this systematic review is to summarize the most recent evidence regarding the use of immune checkpoint inhibitors, in a neoadjuvant and adjuvant setting, in the treatment of muscle-invasive bladder cancer.
PubMed: 35626149
DOI: 10.3390/cancers14102545 -
Survey of Ophthalmology 2021Dry eye disease (DED) is a common ocular surface condition causing symptoms of significant discomfort, visual disturbance, and pain. With recent advancements, DED has... (Review)
Review
Dry eye disease (DED) is a common ocular surface condition causing symptoms of significant discomfort, visual disturbance, and pain. With recent advancements, DED has become recognized as a chronic self-perpetuating inflammatory condition triggered by various internal and environmental factors. DED has been shown to arise from the activation of both the innate and adaptive immune systems, leading to corneal epithelium and lacrimal gland dysfunction. While the cornea is normally avascular and thus imbued with angiogenic and lymphangiogenic privilege, various DED models have revealed activated corneal antigen-presenting cells in regional lymph nodes, suggesting the formation of new corneal lymphatic vessels in DED. The recent availability of reliable lymphatic cell surface markers such as LYVE-1 has made it possible to study lymphangiogenesis. Accordingly, numerous studies have been published within the last decade discussing the role of lymphangiogenesis in DED pathology. We systematically review the literature to identify and evaluate studies presenting data on corneal lymphangiogenesis in DED. There is considerable evidence supporting corneal lymphangiogenesis as a central mediator of DED pathogenesis. These findings suggest that anti-lymphangiogenic therapeutic strategies may be a viable option for the treatment of DED, a conclusion supported by the limited number of reported clinical trials examining anti-lymphangiogenic modalities in DED.
Topics: Cornea; Dry Eye Syndromes; Humans; Lacrimal Apparatus; Lymphangiogenesis; Lymphatic Vessels
PubMed: 33811911
DOI: 10.1016/j.survophthal.2021.03.007 -
Frontiers in Medicine 2023Glioblastoma is the most common and malignant primary brain tumour with median survival of 14.6 months. Personalised medicine aims to improve survival by targeting...
INTRODUCTION
Glioblastoma is the most common and malignant primary brain tumour with median survival of 14.6 months. Personalised medicine aims to improve survival by targeting individualised patient characteristics. However, a major limitation has been application of targeted therapies in a non-personalised manner without biomarker enrichment. This has risked therapies being discounted without fair and rigorous evaluation. The objective was therefore to synthesise the current evidence on survival efficacy of personalised therapies in glioblastoma.
METHODS
Studies reporting a survival outcome in human adults with supratentorial glioblastoma were eligible. PRISMA guidelines were followed. MEDLINE, Embase, Scopus, Web of Science and the Cochrane Library were searched to 5th May 2022. Clinicaltrials.gov was searched to 25th May 2022. Reference lists were hand-searched. Duplicate title/abstract screening, data extraction and risk of bias assessments were conducted. A quantitative synthesis is presented.
RESULTS
A total of 102 trials were included: 16 were randomised and 41 studied newly diagnosed patients. Of 5,527 included patients, 59.4% were male and mean age was 53.7 years. More than 20 types of personalised therapy were included: targeted molecular therapies were the most studied (33.3%, 34/102), followed by autologous dendritic cell vaccines (32.4%, 33/102) and autologous tumour vaccines (10.8%, 11/102). There was no consistent evidence for survival efficacy of any personalised therapy.
CONCLUSION
Personalised glioblastoma therapies remain of unproven survival benefit. Evidence is inconsistent with high risk of bias. Nonetheless, encouraging results in some trials provide reason for optimism. Future focus should address target-enriched trials, combination therapies, longitudinal biomarker monitoring and standardised reporting.
PubMed: 37122327
DOI: 10.3389/fmed.2023.1166104 -
Life Sciences Jan 2021Although anti-inflammatory properties are attributed to sesquiterpene lactones (SL), cutaneous hypersensitivity reactions are proposed as limitations for SL-based...
Although anti-inflammatory properties are attributed to sesquiterpene lactones (SL), cutaneous hypersensitivity reactions are proposed as limitations for SL-based therapies. Thus, the impact of SL on the skin and skin-related cells was systematically reviewed. Studies indexed in electronic databases were screened from the PRISMA strategy. The risk of bias in all studies was verified from the SYRCLE's tool. Thirty original studies were recovered and analyzed. Mice and guinea pig, keratinocytes and fibroblasts were predominantly investigated from in vivo and in vitro studies, respectively. In vivo studies indicated that most SL induced contact dermatitis associated with edema, erythema, and inflammatory infiltrate. Conversely, in vitro evidence was consistent with a dose-dependent anti-inflammatory effect of SL in response to reduced cytokines, 5-LOX, and COX-2 levels or activity in keratinocytes, fibroblasts, macrophages and dendritic cells; which are events potentially triggered by downregulation of gene expression and/or inhibition of the NF-κB signaling pathway. In vivo studies presented uncertain to high-risk of bias mainly associated with underreporting of randomization and experimental blinding. The current evidence supports potent cutaneous immunomodulatory properties of SL. Although in vitro and in vivo studies indicate opposite anti- or proinflammatory effects, this contradiction exhibits a dose-dependent component. In addition, the anti-inflammatory pathways activated by SL are better understood from in vitro evidence. However, additional studies are required to elucidating specific anti-inflammatory and proinflammatory mechanisms triggered by SL in vivo. Thus, controlling the sources of bias described in this review can contribute to improving the quality of the evidence in further investigations.
Topics: Animals; Anti-Inflammatory Agents; Dermatitis, Contact; Dose-Response Relationship, Drug; Guinea Pigs; Humans; Lactones; Mice; NF-kappa B; Sesquiterpenes; Skin
PubMed: 33278385
DOI: 10.1016/j.lfs.2020.118815 -
Journal of Personalized Medicine Dec 2021Liquid biopsy is an accessible, non-invasive diagnostic tool for advanced prostate cancer (PC) patients, potentially representing a real-time monitoring test for tumor... (Review)
Review
Liquid biopsy is an accessible, non-invasive diagnostic tool for advanced prostate cancer (PC) patients, potentially representing a real-time monitoring test for tumor evolution and response to treatment through the analysis of circulating tumor cells (CTCs) and exosomes. We performed a systematic literature review (PRISMA guidelines) to describe the current knowledge about PD-L1 expression in liquid biopsies of PC patients: 101/159 (64%) cases revealed a variable number of PD-L1+ CTCs. Outcome correlations should be investigated in larger series. Nuclear PD-L1 expression by CTCs was occasionally associated with worse prognosis. Treatment (abiraterone, enzalutamide, radiotherapy, checkpoint-inhibitors) influenced PD-L1+ CTC levels. Discordance in PD-L1 status was detected between primary vs. metastatic PC tissue biopsies and CTCs vs. corresponding tumor tissues. PD-L1 is also released by PC cells through soluble exosomes, which could inhibit the T cell function, causing immune evasion. PD-L1+ PC-CTC monitoring and genomic profiling may better characterize the ongoing aggressive PC forms compared to PD-L1 evaluation on primary tumor biopsies/prostatectomy specimens (sometimes sampled a long time before recurrence/progression). Myeloid-derived suppressor cells and dendritic cells (DCs), which may have immune-suppressive effects in tumor microenvironment, have been found in PC patients circulation, sometimes expressing PD-L1. Occasionally, their levels correlated to clinical outcome. Enzalutamide-progressing castration-resistant PC patients revealed increased PD-1+ T cells and circulating PD-L1/2+ DCs.
PubMed: 34945784
DOI: 10.3390/jpm11121312 -
Frontiers in Immunology 2021MiRNA is a type of small non-coding RNA, by regulating downstream gene expression that affects the progression of multiple diseases, especially cancer. MiRNA can...
MiRNA is a type of small non-coding RNA, by regulating downstream gene expression that affects the progression of multiple diseases, especially cancer. MiRNA can participate in the biological processes of tumor, including proliferation, invasion and escape, and exhibit tumor enhancement or inhibition. The tumor immune microenvironment contains numerous immune cells. These cells include lymphocytes with tumor suppressor effects such as CD8+ T cells and natural killer cells, as well as some tumor-promoting cells with immunosuppressive functions, such as regulatory T cells and myeloid-derived suppressor cells. MiRNA can affect the tumor immune microenvironment by regulating the function of immune cells, which in turn modulates the progression of tumor cells. Investigating the role of miRNA in regulating the tumor immune microenvironment will help elucidate the specific mechanisms of interaction between immune cells and tumor cells, and may facilitate the use of miRNA as a predictor of immune disorders in tumor progression. This review summarizes the multifarious roles of miRNA in tumor progression through regulation of the tumor immune microenvironment, and provides guidance for the development of miRNA drugs to treat tumors and for the use of miRNA as an auxiliary means in tumor immunotherapy.
Topics: Animals; Antineoplastic Agents; Dendritic Cells; Disease Progression; Humans; Immunotherapy; Killer Cells, Natural; Lymphocytes, Tumor-Infiltrating; MicroRNAs; Myeloid-Derived Suppressor Cells; Neoplasms; Phenotype; Tumor Escape; Tumor Microenvironment; Tumor-Associated Macrophages
PubMed: 34084160
DOI: 10.3389/fimmu.2021.624725 -
Diagnostic Pathology Aug 2022Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm of mesenchymal origin. FDCS of gastrointestinal tract (GI) are exceedingly uncommon.
BACKGROUND
Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm of mesenchymal origin. FDCS of gastrointestinal tract (GI) are exceedingly uncommon.
CASE PRESENTATION
We report the first case of classic type FDCS in a 34-year-old male with Birt-Hogg-Dubé syndrome, which presented as a mass at the ileo-cecal junction. He received no further treatment after resection and remained disease free for 3.5 years. We further analyze and review the clinical and pathologic findings of 33 cases of GI tract FDCS reported in the literature.
CONCLUSIONS
There are two distinct subtypes of FDCS in the GI tract: the classic type occurs in relatively younger patients (mean = 45.3 years) without Epstein-Barr virus (EBV) association, and behaves more aggressively; the inflammatory subtype presents as colonic polypoid tumor in older patients (mean = 60.7 years) and is EBV positive. The clinical outcome in the latter group appears favorable although mortality rate is not necessarily low.
Topics: Adult; Aged; Humans; Male; Dendritic Cell Sarcoma, Follicular; Disease-Free Survival; Epstein-Barr Virus Infections; Gastrointestinal Tract; Herpesvirus 4, Human
PubMed: 35941667
DOI: 10.1186/s13000-022-01246-z -
Frontiers in Molecular Biosciences 2022Immunoglobulin E (IgE)-mediated allergies are increasing in prevalence, with IgE-mediated food allergies currently affecting up to 10% of children and 6% of adults...
Immunoglobulin E (IgE)-mediated allergies are increasing in prevalence, with IgE-mediated food allergies currently affecting up to 10% of children and 6% of adults worldwide. The mechanisms underpinning the first phase of IgE-mediated allergy, allergic sensitization, are still not clear. Recently, the potential involvement of lipids in allergic sensitization has been proposed, with reports that they can bind allergenic proteins and act on immune cells to skew to a T helper type 2 (Th2) response. The objective of this systematic review is to determine if there is strong evidence for the role of lipids in allergic sensitization. Nineteen studies were reviewed, ten of which were relevant to lipids in allergic sensitization to food allergens, nine relevant to lipids in aeroallergen sensitization. The results provide strong evidence for the role of lipids in allergies. Intrinsic lipids from allergen sources can interact with allergenic proteins to predominantly enhance but also inhibit allergic sensitization through various mechanisms. Proposed mechanisms included reducing the gastrointestinal degradation of allergenic proteins by altering protein structure, reducing dendritic cell (DC) uptake of allergenic proteins to reduce immune tolerance, regulating Th2 cytokines, activating invariant natural killer T (iNKT) cells through CD1d presentation, and directly acting upon toll-like receptors (TLRs), epithelial cells, keratinocytes, and DCs. The current literature suggests intrinsic lipids are key influencers of allergic sensitization. Further research utilising human relevant models and clinical studies are needed to give a reliable account of the role of lipids in allergic sensitization.
PubMed: 35495627
DOI: 10.3389/fmolb.2022.832330