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Clinical and Experimental Rheumatology 2013Interleukin-6 (IL-6) may play a role in the pathogenesis of SSc. C-reactive protein (CRP), an acute phase reactant induced by IL-6, may be a prognostic marker in SSc.... (Review)
Review
OBJECTIVES
Interleukin-6 (IL-6) may play a role in the pathogenesis of SSc. C-reactive protein (CRP), an acute phase reactant induced by IL-6, may be a prognostic marker in SSc. The goal of this systematic review was to address the significance and clinical application of IL-6 and CRP in systemic sclerosis (SSc).
METHODS
A literature search was conducted to identify English-language original articles within PubMed, Scopus, and Medline database from inception to May 30, 2013 using keywords 'systemic sclerosis or scleroderma and C-reactive protein or interleukin-6'.
RESULTS
The search resulted in 156 relevant articles. Some single nucleotide polymorphisms and gene-gene interactions affect SSc predisposition, manifestation and expression of IL-6. Studies in animal models show IL-6 and IL-6 trans-signalling are involved in SSc disease development. Derangements of T and B cells function regulate IL-6 in SSc pathogenesis. Fibroblasts, T/B cells, monocytes, macrophages, dendritic cells and endothelial cells participate in IL-6 expression and interact with each other resulting in tissue sclerosis. Up-regulation of serum IL-6 and CRP levels are evident in SSc patients and associated with disease activity, severity, disability, worse outcome and reduced survival. Targeted IL-6 therapy in SSc has occurred in small cases series and within a multi-site trial that is under way.
CONCLUSIONS
Studies show IL-6 and CRP are important in SSc both in pathogenesis and clinical manifestations and may be useful indicators of disease activity, severity, and poor prognosis. IL-6 could be a relevant treatment target in SSc.
Topics: C-Reactive Protein; Humans; Interleukin-6; Scleroderma, Systemic
PubMed: 23910616
DOI: No ID Found -
Orphanet Journal of Rare Diseases Jan 2021Langerhans cell histiocytosis (LCH) is a rare disease that originates from the uncontrolled proliferation and accumulation of bone marrow-derived immature myeloid... (Review)
Review
BACKGROUND
Langerhans cell histiocytosis (LCH) is a rare disease that originates from the uncontrolled proliferation and accumulation of bone marrow-derived immature myeloid dendritic cells. Dendritic cells are a type of histiocyte that play an important role in the human immune system and are found in the bone, skin, stomach, eyes, intestines, and lungs.
OBJECTIVE
This systematic review aimed to collect and report published case reports of rare bone disease caused by LCH to avoid misdiagnoses or delays in diagnosis.
METHODS
We systematically searched Scopus, PubMed, Embase, and Web of Sciences from August 1, 2000 to December 31, 2019. Studies reporting cases of LCH with rare bone involvement were included.
RESULTS
We identified 60 articles including 64 cases. Of the identified cases, 31 (48.4%) involved children, and 33 (51.6%) involved adults. Additionally, 46.9% (30 individuals) were from Asian countries. The mean age of the children was 7.6 ± 4.3 years and that of the adults was 36 ± 12 years. The findings indicated that unifocal bone involvements were the most prevalent form of the disease (68.7%), and, overall, the skull and chest wall were the most commonly affected bones in both adults and children. The spine and long bones were the second most commonly affected bones in children, and the spine and jaw were the second most commonly affected bones in adults. Pain and swelling were the most frequent presenting signs among the investigated cases, and loss of consciousness, myelopathy, nerve palsy, visual loss, torticollis and clicking sounds were rare signs. Osteolytic lesions were the most frequent radiologic feature (62.5%), and intracranial hemorrhage, fluid-fluid level, dura and intracranial extension and pathologic fractures were rare radiological features. Total excision, curettage and observation in the unifocal group of patients and systemic chemotherapy in the other groups (i.e., multifocal and multisystem) were the most frequent management approaches. The recovery rates of the unifocal and multifocal groups were 77.3% and 81.8%, respectively, while that of the multisystem group was 55.5%. The rates of recurrence and mortality in the multisystem group were 11% and were higher than those in the other groups.
CONCLUSIONS
LCH is a rare disease that can affect any organ in the human body. However, bone is the most commonly involved organ, and rare bone involvements may be the first or only symptom of the disease due to the rarity of such lesions; a lack of familiarity with them may result in misdiagnosis or delayed diagnosis.
Topics: Adult; Asia; Bone Diseases; Child; Child, Preschool; Histiocytosis, Langerhans-Cell; Humans; Retrospective Studies; Skull
PubMed: 33388073
DOI: 10.1186/s13023-020-01625-z -
European Journal of Cancer (Oxford,... Jan 2021Therapeutic cancer vaccination is an area of interest, even though promising efficacy has not been demonstrated so far. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Therapeutic cancer vaccination is an area of interest, even though promising efficacy has not been demonstrated so far.
DESIGN
A systematic review and meta-analysis was conducted to evaluate vaccines' efficacy on breast cancer (BC) and ovarian cancer (OC) patients. Our search was based on the PubMed electronic database, from 1st January 2000 to 4th February 2020.
OBJECTIVE
response rate (ORR) was the primary end-point of interest, while progression-free survival (PFS), overall survival (OS) and toxicity were secondary end-points. Analysis was performed separately for BC and OC patients. Pooled ORRs were estimated by fixed or random effects models, depending on the detected degree of heterogeneity, for all studies with more than five patients. Subgroup analyses by vaccine type and treatment schema as well as sensitivity analyses, were implemented.
RESULTS
Among 315 articles initially identified, 67 were eligible for our meta-analysis (BC: 46, 1698 patients; OC: 32, 426 patients; where both BC/OC in 11). Dendritic-cell and peptide vaccines were found in more studies, 6/10 BC and 10/13 OC studies, respectively. In our primary BC analysis (21 studies; 428 patients), the pooled ORR estimate was 9% (95%CI[5%,13%]). The primary OC analysis (12 studies; 182 patients), yielded pooled ORR estimate of 4% (95%CI[1%,7%]). Similar were the results derived in sensitivity analyses. No statistically significant differences were detected by vaccine type or treatment schema. Median PFS was 2.6 months (95% confidence interval (CI)[1.9,2.9]) and 13.0 months (95%CI[8.5,16.3]) for BC and OC respectively, while corresponding median OS was 24.8 months (95%CI[15.0,46.0]) and 39.0 months (95%CI[31.0,49.0]). In almost all cases, the observed toxicity was only moderate.
CONCLUSION
Despite their modest results in terms of ORR, therapeutic vaccines in the last 20 years display relatively long survival rates and low toxicity. Since a plethora of different approaches have been tested, a better understanding of the underlying mechanisms is needed in order to further improve vaccine efficacy.
Topics: Breast Neoplasms; Cancer Vaccines; Female; Humans; Ovarian Neoplasms; Time Factors
PubMed: 33221598
DOI: 10.1016/j.ejca.2020.10.014 -
Current Cancer Drug Targets 2014CD40 is a co-stimulatory molecule belonging to the tumor necrosis factor superfamily and is essential in activation of dendritic cells. Dendritic cells (DCs) are... (Review)
Review
CD40 is a co-stimulatory molecule belonging to the tumor necrosis factor superfamily and is essential in activation of dendritic cells. Dendritic cells (DCs) are antigen-presenting cells capable of initiating cytotoxic T-lymphocyte immune response against cancer cells. However, there are few studies on the characterization of DCs in cancer, specifically their expression of CD40, despite its implication in cancer immunotherapy. We reviewed available data on the expression of CD40 on DCs in various cancers, and its implications for cancer immunotherapy. A systematic review on CD40 expression on DCs in cancer was performed with reference to preferred reporting items for systematic reviews and meta-analyses (PRISMA). Studies that satisfied the inclusion and exclusion criteria were 21 out of 927. Variations in type and status of the cancers, source of DCs and methodology for detecting CD40 expression amongst the studies resulted in contrasting results. DCs generally expressed low CD40 in tumor infiltrating DCs (tiDCs), in DCs derived by in vitro culture from blood monocytes using cytokine stimulation (MoDCs) and in DCs exposed in vitro to tumor cells lines; the studies suggested that CD40 expression in DCs is impaired in cancer particularly in metastatic disease. However, DCs identified in fresh peripheral blood mononuclear cells (PBMC) expressed higher numbers of CD40 positive cells in some cancer patients, which could be due to tumor-derived factors leading to partially-stimulated DCs. The results provide evidence that some cancer patients may show partial systemic DC activation and expression of increased CD40 in response to the presence of tumor but that such activity may become abortive in the presence of factors produced by the tumor. This review has thus identified key papers on CD40 expression on DCs in various cancers and discusses the limitations and contrasting results of these studies in relation to variations in methodology. The results highlight the need for further studies on the role of CD40-CD40 ligand pathway to inform cancer treatment.
Topics: Animals; CD40 Antigens; Dendritic Cells; Down-Regulation; Humans; Neoplasm Metastasis; Neoplasm Proteins; Neoplasms
PubMed: 25163469
DOI: 10.2174/1568009614666140828103253 -
World Journal of Gastroenterology Jan 2014To investigate whether autologous dendritic cell (DC)-cytokine-induced killer (CIK) cell therapy is able to improve the therapeutic efficacy of chemotherapy in colon... (Meta-Analysis)
Meta-Analysis Review
AIM
To investigate whether autologous dendritic cell (DC)-cytokine-induced killer (CIK) cell therapy is able to improve the therapeutic efficacy of chemotherapy in colon cancer.
METHODS
We conducted a systematic review of published papers from the sources of MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, the Wanfang Database, the China Science and Technology Periodical Database and China Journal Net. Published data were extracted independently by two authors using predefined database templates. The quality of the data from individual papers was also assessed. The effects of chemotherapy were compared with those of chemotherapy in combination with DC-CIK immunotherapy. The pooled analysis was performed using the data from random or fixed-effect models.
RESULTS
Seven trials matched our inclusion criteria (n = 533). The overall analysis showed significant survival benefit [one-year overall survival (OS), P < 0.0001; two-year OS, P = 0.009; three-year OS, P = 0.002] in favor of DC-CIK immunotherapy combined with chemotherapy. Disease-free survival (DFS) rate was improved after the combination of DC-CIK immunotherapy and chemotherapy (one-year DFS, P < 0.0001; two-year DFS, P = 0.002; three-year DFS, P = 0.02). An improved overall response rate (P = 0.009) was also observed in patients who received DC-CIK therapy. Furthermore, the analysis of T-lymphocyte subsets in peripheral blood indicated that the number of CD4⁺ T cells significantly increased in the DC-CIK plus chemotherapy group (P < 0.05).
CONCLUSION
The combination of DC-CIK immunotherapy and chemotherapy was superior in prolonging the survival time and enhancing immunological responses.
Topics: Antineoplastic Agents; Chemotherapy, Adjuvant; China; Colonic Neoplasms; Cytokine-Induced Killer Cells; Dendritic Cells; Humans; Immunotherapy, Adoptive; Survival Analysis; Time Factors; Treatment Outcome
PubMed: 24574784
DOI: 10.3748/wjg.v20.i4.1095 -
Biomedical and Environmental Sciences :... Aug 2010Age-related increment of the prevalence of CD4(+)CD25(+) regulatory T (Treg) cells were described controversially, and whether such changes explain immune dysfunction in... (Review)
Review
OBJECTIVE
Age-related increment of the prevalence of CD4(+)CD25(+) regulatory T (Treg) cells were described controversially, and whether such changes explain immune dysfunction in the elderly is still unclear. The aim of this systematic review is to evaluate the role of the Tregs in immunosenescence.
METHODS
Medline and manual searches were performed to identify all published epidemiological and animal studies investigating the efficacy of the association between immunosenescence and Treg cells.
RESULTS
It was founded that the frequency, phenotypic characteristics, and number/function of Tregs were altered significantly with aging. Medical conditions in individuals with advanced ageas well as apoptosis intensity of Treg cells had an impact on the accumulation of Tregs which in turn could deteriorate cytotoxic activity of CD8(+) T and NK cells and production of IL-2. The range of immune cells that could be suppressed by Treg cells was quite wide and covered CD4(+)CD25(+) T cells, NK cells, dendritic cells and even monocytes. These changes were observed both in humans and experimental animals. Besides, it was believed that frequency of Tregs increased with age and was accompanied by intensified suppressive activity for Tregs in patients, for example, with Alzheimer disease (AD) and Parkinson disease (PD). The impaired condition of CD4(+) T cells, so-called immunosenescence, rendered transplant recipients less responsive to an allogeneic kidney graft, an effect that was limited to transplant recipients who were aged over 60 years.
CONCLUSIONS
Treg cells are associated with immunosenescence. All these changes contribute to the aging-related decline of immune responses and lead to the higher risk of immune-mediated diseases, cancer or infections in aged individuals.
Topics: Aging; Animals; CD4 Antigens; Humans; Interleukin-2 Receptor alpha Subunit; T-Lymphocytes, Regulatory
PubMed: 20934123
DOI: 10.1016/S0895-3988(10)60072-4 -
Asian Journal of Surgery Jun 2023
Meta-Analysis
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Cytokines; Immunotherapy; Combined Modality Therapy; Dendritic Cells
PubMed: 36599723
DOI: 10.1016/j.asjsur.2022.12.049 -
Frontiers in Immunology 2021Breast cancer (BC) prevention remains the ultimate cost-effective method to reduce the global burden of invasive breast cancer (IBC). To date, surgery and...
Breast cancer (BC) prevention remains the ultimate cost-effective method to reduce the global burden of invasive breast cancer (IBC). To date, surgery and chemoprevention remain the main risk-reducing modalities for those with hereditary cancer syndromes, as well as high-risk non-hereditary breast lesions such as ADH, ALH, or LCIS. Ductal carcinoma (DCIS) is a preinvasive malignant lesion of the breast that closely mirrors IBC and, if left untreated, develops into IBC in up to 50% of lesions. Certain high-risk patients with DCIS may have a 25% risk of developing recurrent DCIS or IBC, even after surgical resection. The development of breast cancer elicits a strong immune response, which brings to prominence the numerous advantages associated with immune-based cancer prevention over drug-based chemoprevention, supported by the success of dendritic cell vaccines targeting HER2-expressing BC. Vaccination against BC to prevent or interrupt the process of BC development remains elusive but is a viable option. Vaccination to intercept preinvasive or premalignant breast conditions may be possible by interrupting the expression pattern of various oncodrivers. Growth factors may also function as potential immune targets to prevent breast cancer progression. Furthermore, neoantigens also serve as effective targets for interception by virtue of strong immunogenicity. It is noteworthy that the immune response also needs to be strong enough to result in target lesion elimination to avoid immunoediting as it may occur in IBC arising from DCIS. Overall, if the issue of vaccine targets can be solved by interrupting premalignant lesions, there is a potential to prevent the development of IBC.
Topics: Animals; Antigens, Neoplasm; Breast Carcinoma In Situ; Breast Neoplasms; Cancer Vaccines; Carcinoma, Intraductal, Noninfiltrating; Disease Progression; Female; Humans; Neoplasm Invasiveness; Precancerous Conditions; Tumor Microenvironment; Vaccination
PubMed: 34899753
DOI: 10.3389/fimmu.2021.786286 -
Cureus Aug 2023Tumor necrosis factor-alpha (TNF-α) inhibitors have been shown to be well tolerated among patients with rheumatoid arthritis, inflammatory bowel disease, and psoriasis.... (Review)
Review
Tumor necrosis factor-alpha (TNF-α) inhibitors have been shown to be well tolerated among patients with rheumatoid arthritis, inflammatory bowel disease, and psoriasis. Meanwhile, more recently, clinical practice and research efforts have uncovered increasing cases of psoriatic lesion development tied to initiating treatment with a TNF-α inhibitor. The underlying mechanisms associated with this occurrence have yet to be fully elucidated. A review and analysis of cases of paradoxical psoriasis currently published in the literature is warranted. In addition, exploring possible mechanisms of action and potential treatment options associated with favorable outcomes is much needed. A systematic literature review was performed utilizing PubMed and Google Scholar databases (1992-present), in which 106 cases of paradoxical psoriasis were reviewed. The most common morphology developed was plaque psoriasis vulgaris. There was a female predominance (61.3%), and the most common underlying autoimmune disease was rheumatoid arthritis (45.3%). In addition, the most commonly associated drug with the onset of psoriatic lesions was infliximab (62.3%). Furthermore, the findings suggest that the most well-supported mechanism of action involves the uncontrolled release of interferon-alpha (IFN-α) from plasmacytoid dendritic cells (pDCs) after TNF-α inhibition. While TNF-α inhibitors have been shown to have great benefits to patients with rheumatologic diseases, cases of paradoxical psoriasis demonstrate the importance of close monitoring of patients on TNF-α inhibitors to allow for early recognition, treatment, and potentially change to a different mechanism of action of the medication used to prevent further progression of the inflammatory lesions.
PubMed: 37664349
DOI: 10.7759/cureus.42791 -
Clinical NeuropharmacologyThe efficacy of dendritic cell vaccine for newly diagnosed glioblastoma remains controversial. We conduct a systematic review and meta-analysis to explore the influence... (Meta-Analysis)
Meta-Analysis
The efficacy of dendritic cell vaccine for newly diagnosed glioblastoma remains controversial. We conduct a systematic review and meta-analysis to explore the influence of dendritic cell vaccine on treatment efficacy for newly diagnosed glioblastoma. We search PubMed, EMBASE, Web of science, EBSCO, and Cochrane library databases through December 2019 for randomized controlled trials assessing the efficacy and safety of dendritic cell vaccine for newly diagnosed glioblastoma. This meta-analysis is performed using the random effect model. Three randomized controlled trials are included in the meta-analysis. Overall, compared with control group for newly diagnosed glioblastoma, dendritic cell vaccine shows no substantial effect on median overall survival [standard mean difference, 0.11; 95% confidence interval (CI), -0.18 to 0.41; P = 0.45], median progression-free survival (standard mean difference, 0.12; 95% CI, -0.24 to 0.48; P = 0.50), progression-free survival rate [risk ratio (RR), 1.29; 95% CI, 0.82-2.04; P = 0.27], overall survival rate (RR, 1.29; 95% CI, 0.61-2.72; P = 0.50), or nervous system disorders (RR, 0.80; 95% CI, 0.59-1.08; P = 0.14). Dendritic cell vaccine may provide no obvious benefits for the newly diagnosed glioblastoma.
Topics: Dendritic Cells; Glioblastoma; Humans; Randomized Controlled Trials as Topic; Treatment Outcome; Vaccines
PubMed: 34767325
DOI: 10.1097/WNF.0000000000000452