Evaluation of cell adhesion molecules (LFA-1 and L-selectin) in ankylosing spondylitis patients after treatment with ß-D-mannuronic acid (M2000).

Background & objectives: To examine ß-D-mannuronic acid (M2000) effects on L-selectin shedding and leucocyte function-associated antigen-1 (LFA-1) expression as mechanisms of action of this drug in patients with ankylosing spondylitis (AS). Methods: To investigate the molecular consequences of ß-D-mannuronic acid on L-selectin shedding, flow cytometry method was used. Furthermore, the effect of it on LFA-1 gene expression was analyzed by using quantitative real time (qRT)-PCR technique. Results: The LFA-1 expression in patients with AS was higher than controls (P=0.046). The LFA-1 expression after 12 wk therapy with ß-D-mannuronic acid was meaningfully decreased (P=0.01). After 12 wk treatment with ß-D-mannuronic acid, the frequency of CD62L-expressing CD4+ T cells in patients with AS, was not considerably altered, compared to the patients before therapy (P=0.5). Furthermore, after 12 wk therapy with ß-D-mannuronic acid, L-selectin expression levels on CD4+ T-cells in patients with AS, were not remarkably changed, compared to the expression levels of these in patients before treatment (P=0.2). Interpretation & conclusions: The results of this study for the first time showed that ß-D-mannuronic acid can affect events of adhesion cascade in patients with AS. Moreover, ß-D-mannuronic acid presented as an acceptable benefit to AS patients and could aid in the process of disease management.

Targeting of circulating Th17 cells by ß-D-mannuronic acid (M2000) as a novel medication in patients with rheumatoid arthritis.

OBJECTIVE: This study aimed at investigating the inhibitory effect of ß-D-mannuronic acid (M2000) on the Th17 circulating levels and IL-17 a related cytokine in rheumatoid arthritis (RA) patients. METHODS: The study included 27 patients with RA who had failed response to treatment. All patients were treated orally by M2000 at a dose of 500 mg twice daily for 12 weeks (Clinical trial identifier: IRCT2014011213739N2). The patients based on anti-tumor necrosis factor alpha (TNFα) blocker treatment were classified into two groups (conventional group and etanercept group). They were then allowed to continue their treatment excluding non-steroidal anti-inflammatory drugs (NSAIDs). The frequency of circulating Th17 cells and IL-17 serum level were determined before and 12 weeks after M2000 therapy and were compared to the healthy controls by using flow cytometry analysis and ELISA method, respectively. RESULTS: At baseline, higher circulating Th17 and IL-17 serum levels were significantly observed in both groups of RA patients than in the healthy controls (all P < 0.001). The frequency of Th17 cells significantly decreased in the conventional group as well as in the etanercept group after M2000 therapy but the level of reduction was higher in the conventional group compared to the etanercept group (P < 0.03 and P < 0.04, respectively). The IL-17 serum level significantly decreased in both groups after M2000 therapy (P < 0.01 and P < 0.02, respectively). Furthermore, the frequency of Th17 cells was positively correlated with Disease Activity Score (DAS28) (r = 0.34, P = 0.02). CONCLUSION: M2000 shows the inhibitory effect on the frequency of circulating Th17 cells as well as in the production of IL-17 in RA patients.

The effects of ß-D-mannuronic acid (M2000), as a novel NSAID, on COX1 and COX2 activities and gene expression in ankylosing spondylitis patients and the murine monocyte/macrophage, J774 cell line.

Ankylosing spondylitis (AS) is a debilitating chronic inflammatory disease with genetic predisposition, which is characterized by the involvement of spine and sacroiliac joints. Due to the relatively unsuccessful treatments, we designed ß-D-mannuronic (M2000) with the beneficial effects in various experimental models as a novel non-steroidal anti-inflammatory drug (NSAID). The aims of our present study were: first, to compare the therapeutic effects of M2000, as a novel designed NSAID, with naproxen and placebo in Iranian patients with AS during 12 weeks; second, to evaluate the effect of M2000 on gene expression of cyclooxygenase enzyme (COX-1/COX-2), a key enzyme in the initiation of inflammatory pathways in AS patients; and third, to assess the activity of COX-1 and COX-2 enzymes in the presence/absence of M2000 at the different doses in the murine macrophage, J774 cell line. This was a sub-study of phase II, randomized, placebo-controlled trial with three treatment arms: M2000, naproxen, and placebo. The outcome measures were the mean changes from baseline to week 12. The gene expression was assessed by real-time PCR. The COX-1 and COX-2 activities were evaluated by ELISA in J774 cell line induced by LPS and arachidonic acid (AA). Our findings demonstrated that M2000 had beneficial therapeutic effects on pain, stiffness, and inflammation, whereas no adverse effects were observed following the use of M2000 after 12 weeks. The analysis of gene expression showed that M2000 could effectively reduce the expression levels of COX-1 and COX-2 in comparison with untreated patients. In addition, the enzymatic activities in the presence of M2000 were significantly less than LPS- and AA-treated groups. Our results indicate that M2000, as a novel designed NSAID with immunosuppressive properties, can be considered as one of the therapeutic options for the treatment of inflammatory diseases without adverse events. Clinical trial identifier IRCT2013062213739N1/ http://www.IRCT.ir .

A phase I/II randomized, controlled, clinical trial for assessment of the efficacy and safety of ß-D-mannuronic acid in rheumatoid arthritis patients.

BACKGROUND: Following the potent efficacy of ß-D-mannuronic acid (M2000) in phase I/II trial in ankylosing spondylitis patients, the present clinical trial was conducted to evaluate the efficacy, safety, and tolerability of this novel drug in rheumatoid arthritis (RA) patients who had inadequate response to conventional therapy. METHOD: The study was a 12-week randomized, controlled, phase I/II clinical trial with two treatment arms: M2000 and conventional treatment. Patients who had RA according to the modified American College of Rheumatology (ACR) criteria, with active disease at baseline also inadequate response to conventional therapy, were enrolled in this study. M2000 was administrated at a dose of two capsules (500 mg) per day orally during a period of 12 weeks. The primary endpoint was the proportion of patients fulfilling the ACR 20% improvement criteria after 12 weeks of M2000 therapy. Moreover, the patients were also followed up for safety. RESULTS: There were no statistically significant differences between treatment and conventional groups at baseline characteristics. The ACR20 response rate was significantly higher among M2000-treated patients than conventional-treated control, so that 74% of patients in treatment group showed an ACR20 response after 12 weeks of M2000 therapy (74 versus 16%; P = 0.011). 10% of M2000-treated patients and 57.1% of conventional-treated patient's adverse events occurred during this study. CONCLUSION: Treatment with M2000 in combination with conventional therapy showed a significantly superior efficacy along with a high safety profile compared to conventional-treated patients. Thereby, M2000 might be suggested as a suitable option in the treatment of RA.

Preclinical and pharmacotoxicology evaluation of α-l-guluronic acid (G2013) as a non-steroidal anti-inflammatory drug with immunomodulatory property.

CONTEXT: Therapeutic effects of α-l-guluronic acid with the greatest tolerability and efficacy (G2013) have been shown in experimental model of multiple sclerosis and other in vitro and in vivo examinations regarding α-l-guluronic acid; there are no toxicological researches on its safety although the pharmacological impacts have been recorded. OBJECTIVE: This study was designed to determine the acute and sub chronic toxicity of α-l-guluronic acid in healthy male and female BALB/c mice. MATERIALS AND METHODS: For the acute toxicity study, the animals orally received five different single doses of α-l-guluronic acid and were kept under observation for 14 d. In the sub-chronic study, 24 male and female BALB/c mice were divided into four groups and treated daily with test substance preparation at dose levels of 0, 50, 250, and 1250 mg/kg body weight for at least 90 consecutive days. The mortality, body weight changes, clinical signs, hematological and biochemical parameters, gross findings, histopathological, and organs weight determinants were monitored during this study. RESULTS: The results of acute toxicity indicated that the LD50 of α-l-guluronic acid is 4.8 g/kg. We found no mortality or abnormality in clinical signs, body weight, relative organs weight, or necropsy in any of the animals in the subchronic study. Additionally, the results showed no significant difference in hematological, biochemical, and histopathological parameters in rats. CONCLUSIONS: Our results suggest that α-l-guluronic acid has high safety when administered orally in animals.

Preclinical assessment of ß-d-mannuronic acid (M2000) as a non-steroidal anti-inflammatory drug.

CONTEXT: ß-d-Mannuronic acid (M2000) has shown its therapeutic effects with the greatest tolerability and efficacy in various experimental models such as experimental autoimmune encephalomyelitis (EAE), adjuvant induced arthritis (AIA), nephrotic syndrome, and acute glomerulonephritis. Despite pharmacological effects of ß-D-mannuronic acid, there have been no systematic toxicological studies on its safety so far. OBJECTIVE: The study was designed to determine the acute and subchronic toxicity of ß-D-mannuronic acid, an anti-inflammatory agent, in healthy male NMRI mice and Wistar rats, respectively. MATERIALS AND METHODS: For the acute toxicity study, the animals received orally five different single doses of ß-D-mannuronic acid and were kept under observation for 14 d. In the subchronic study, 24 Wistar male rats were divided into four groups and were treated orally (gavage) once daily with test substance preparation at dose levels of 0, 50, 250, and 1250 mg/kg body weight for at least 63 consecutive days (9 weeks). Mortality, clinical signs, body weight changes, hematological and biochemical parameters, gross findings, organ weights, and histopathological determinations were monitored during the study. RESULTS: The results of acute toxicity indicated that the LD50 of ß-D-mannuronic acid is 4.6 g/kg. We found no mortality and no abnormality in clinical signs, body weight, relative organ weights, or necropsy in any of the animals in the subchronic study. Additionally, the results showed no significant difference in hematological, biochemical, and histopathological parameters in rats. CONCLUSIONS: Our results suggest that ß-D-mannuronic acid is relatively safe when administered orally in animals.

Upregulation of serum vascular endothelial growth factor and matrix metalloproteinase-3 in patients with oral squamous cell carcinoma.

Vascular endothelial growth factor (VEGF) is known as a fundamental regulator of angiogenesis that accelerates cellular proliferation, vascular permeability, and endothelial cell migration and is an inhibitor of apoptosis. Extracellular matrix degradation by matrix metalloproteinase (MMP) is necessary for endothelial cell proliferation, migration, and metastasis. Accordingly, the objective of the present study was to determine the circulating levels of VEGF and MMP3 and their relation in patients with oral squamous cell carcinoma. Using an ELISA kit, the circulating levels of VEGF and MMP-3 in the sera of 45 patients with oral squamous cell carcinoma (OSCC) and 45 healthy controls were assessed. Mean VEGF levels in the sera of patients with OSCC (122.4 ± 36.1) were significantly higher than those in controls (65.3 ± 23.4); however, no relation was found between VEGF levels and clinicopathologic factors. The serum MMP-3 level in OSCC patients was significantly higher (9.45 ± 4.6 ng/ml, n=45) than that in healthy controls (5.9 ± 3.6 ng/ml, n=45). There was no correlation in serum MMP-3 concentration with clinicopathologic features such as tumor stage, tumor size, nodal status, and histological grade. A significant relationship was found between serum levels of VEGF and MMP3. This study concludes that VEGF and MMP3 may have a potential role in the pathogenesis of OSCC but cannot be used as a tool for monitoring tumor progression. Moreover, the role of VEGF in the regulation of angiogenesis is in part due to activation of MMP-3.

Serum levels of osteopontin as a prognostic factor in patients with oral squamous cell carcinoma.

Osteopontin (OPN) is a multifunctional glycophosphoprotein that was detected in many carcinomas, and it may have a prognostic role. The aim of this study was to determine osteopontin serum levels in patients with oral squamous cell carcinoma (OSCC) and investigated its correlation with clinicopathological features of tumor. Using an ELISA kit, we assessed and compared the circulating levels of OPN in blood serum of 45 oral squamous cell carcinoma patients with 45 healthy control samples. The serum osteopontin level in patients with OSCC was significantly higher (145.8 ± 14.6 ng/ml, n = 45) compared with the healthy controls (53.9 ± 9.6 ng/ml, n = 45, p < 0.001). Mean serum osteopontin level was significantly higher in patients with nodal metastasis (p = 0.03) and higher stage (p = 0.02). Findings of the present study suggest that OPN may have a potential role in pathogenesis of OSCC and it may be used as a tool for monitoring tumor progression.

Positive and negative effects of prostaglandins in Alzheimer's disease.

The aim of this review was to clarify the role of prostaglandins and prostaglandin receptors in the immunopathology of Alzheimer's disease. A PubMed search was done using the key word, 'Alzheimer's disease' in combination with the term 'prostaglandins'. Articles from the past 10 years were preferentially selected but important ones from the past 20 years were also included according to the authors' judgment. Alzheimer's disease is characterized by pathological hallmarks such as extracellular deposition of the amyloid ß-peptide, the appearance of intracellular neurofibrillary tangles, extensive neuronal loss and synaptic changes in the cerebral cortex and hippocampus. These processes induce inflammatory pathways by activating microglia, astrocytes and infiltrating leukocytes that produce inflammatory mediators including cytokines and prostaglandins.Prostaglandins are small lipid mediators derived from arachidonic acid by multi-enzymatic pathways in which cyclooxygenases and phospholipases are the rate-limiting enzymes. In the central nervous system, prostaglandins exhibit either neurotoxic or neuroprotective effects by acting on specific G-protein-coupled receptors that have different subfamilies and differences in their selective agonists, tissue distribution and signal transduction cascades. Further studies on the role of prostaglandins in Alzheimer's disease may contribute to clarification of their neuroprotective actions, which may lead to the development of successful therapeutic strategies.

Evaluation of the genetic diversity of KIR genes in patients with endometrial cancer.

Endometrial cancer (EC) constitutes more than half of all genital cancers in women, with an increasing incidence in different countries. Natural killer cells (NK cells) are kinds of innate immune cells that are controlled by sets of receptors, such as killer cell Ig-like receptors (KIRs), which can inhibit or activate NK cells. In this study, we evaluated the diversity and genetic association of KIRs in confirmed cases of endometrial cancer compared to healthy controls. A total of 151 women with EC and 167 age/race-matched healthy controls were analyzed for KIR genes. Demographic and histopathologic data were gathered in questionnaires, and 16 KIR genes along with two variants of KIR2DS4 (KIR2DS4fl and KIR2DS4del), were genotyped by usingsequence specific primers-polymerase chain reaction (SSP-PCR) method. A comparison between cases and controls revealed that although there were not any significant differences in A haplotype associated genes and also the variants of KIR2DS4 (p >0.05), B haplotype associated genes such as KIR2DS2 and KIR2DL2 decreased significantly in EC patients in comparison with healthy controls (p=0.03 and p=0.01, respectively). Furthermore, we found that EC mostly developed in cases with the AA genotype; however, the carriers of Bx and C4T4 genotypes were less frequent in patients with EC. Our results revealed that KIR2DS2 and KIR2DL2, along with Bx and C4T4 genotypes, have a protective impact against developing endometrial cancer in Iranians.

Investigation of PD-1 gene variants in patients with endometrial cancer: A case-control study.

Objective: To assess the possible association of two single-nucleotide polymorphisms (SNPs), PD-1.3 (+7146G/A) and PD-1.5 (+7785C/T), with endometrial cancer (EC) susceptibility. In addition, the correlations between these SNPs and available clinicopathologic characteristics of patients with EC were investigated. Materials and Methods: In this case-control study, 147 women with pathologically confirmed EC and 258 age- and ethnically matched healthy women were enrolled between June 2019 and May 2022. Genomic DNA was extracted, and genotyping of PD-1.3 (+7146G/A) and PD-1.5 (+7785C/T) SNPs was performed. Haplotype analysis was also performed. Pearson's chi-square test with Yates correction was used to evaluate differences in allele and genotype distributions. The 95% confidence interval and odds ratio were determined using an unconditional logistic regression model. Results: There were no remarkable differences in the allele and genotype distributions of PD-1.3 (rs11568821) and PD-1.5 (rs2227981) between healthy controls and EC patients. However, there was a remarkable difference in the AC haplotype between the control and EC groups. No association was found between the investigated SNPs and the clinicopathologic features of EC. Conclusion: Our results indicated that the aforementioned SNPs were not related to the risk of EC in the southern Iranian population.

Allelic and Genotypic Analysis of LncRNA ANRIL rs4977574 A/G Mutations in Oral Squamous Cell Carcinoma Patients: Insights into Tumor Characteristics and Genotypic Correlations.

Aim: Long noncoding RNAs (lncRNA) ANRIL and its genetic polymorphisms are shown to be associated with the risk of several cancers. However, the single nucleotide polymorphisms (SNPs) of lncRNA ANRIL are not thoroughly assessed in oral squamous cell carcinoma (OSCC) which is the most prevalent cancer in the head and neck area. Thus, this study aimed to assess the association of SNP of lncRNA ANRIL rs4977574 in patients with OSCC. Methods and Materials: 106 blood samples from the patients with OSCC were obtained with a gender- and age-matched control group to evaluate the SNP of rs4977574 of lncRNA ANRIL. The DNA was extracted using the salt-out technique and DNA genotyping was undertaken using specific primer pairs in the tetra-primer ARMS-PCR technique. Eventually, the frequency of wild-type (A) and the mutated allele (G), as well as the genotypes were estimated between the groups of patients with OSCC and healthy individuals. Results: The results of our study indicated no statistically significant difference in the frequency of rs4977574 A/G of lncRNA ANRIL among the patients with OSCC and healthy individuals (p > 0.05). Likewise, no significant difference was found in the genotypes' frequencies (p > 0.05). Nevertheless, the marked association of GG with smaller tumor size and the high level of differentiation of OSCC cells in the presence of AA or AG genotypes were interesting outcomes of this study (p < 0.05). Similarly, all the genotypes AA, AG, and GG were correlated with the site of the occurrence of OSCC. Furthermore, the association of the genotypes with the lymph node metastasis and the tumors stage was not found to be significant (p > 0.05). Conclusions: The results of our study indicate that rs4977574 A/G and its genotypes do not have any direct correlation with the presence of OSCC; however, its association with the smaller tumor size and the level of the cancer cells differentiation could imply its possible indirect role.

Investigation of the Seroprevalence of Antimeasles Immunoglobulin G Antibody in Students at Shiraz University of Medical Sciences.

Measles is an acute, highly contagious disease with a high mortality rate in children. Although vaccination has reduced measles incidence, outbreaks still occur. Therefore, in this study, we aimed to investigate the frequency of antimeasles immunoglobulin G (IgG) antibody (Ab) among students at Shiraz University of Medical Sciences (SUMS). Four hundred fifty SUMS students were enrolled in this cross-sectional study. Information on demographics and measles vaccination history was collected using a questionnaire. Participants were divided into two groups, including A and B, according to routine doses of measles vaccine and the national measles/rubella immunization program. The antimeasles IgG Abs were tested using a commercial Enzyme-Linked Immunosorbent Assay Kit. Participants ranged in age from 18 to 48 years, with a mean age of 22.2 (±4.3). Fifty percent of the subjects were male. Our results showed that 63.6% of the cases were positive for antimeasles IgG Abs. The seroprevalence of IgG Abs between groups A and B did not differ significantly (p = 0.612). There was also no significant correlation between the seroprevalence of antimeasles IgG Abs and the age (p = 0.43) or sex (p = 0.24) of the subjects. The results showed that the frequency of antimeasles IgG Abs is lower than required to prevent the measles virus from circulating. Therefore, a booster vaccination may be necessary.

Serum Level of Vascular Endothelial Growth Factor in Patients with Different Clinical SubtypeS of Oral Lichen Planus.

BACKGROUND: Oral lichen planus is a chronic inflammatory disease with a poorly understood etiology. The role of angiogenesis in the development of different chronic inflammatory diseases is of great concern. Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis. We aimed to evaluate the serum level of VEGF in patients with oral lichen planus compared with normal individuals and consider its clinical significance. METHODS: In this case-control study, 36 serum samples from patients diagnosed with oral lichen planus admitted to the Oral Medicine Department of the School of Dentistry at Shiraz University of Medical Sciences (14 men, 22 women, mean [±SD] age: 38.8 [±6.07] years) and 23 serum samples from healthy individuals (9 men, 14 women, mean [±SD] age: 38.7 [±4.9] years) were collected. VEGF concentration was measured using the ELISA method. The Mann-Whitney test was used for statistical analysis. RESULTS: The serum VEGF level was significantly higher in patients with oral lichen planus compared with the healthy controls (112.97 [±63.2] vs. 66.21 [±56.2] ngr/ml, P<0.001). A similar difference was also observed between the two types of oral lichen planus, being more pronounced in the erosive form (P<0.001). CONCLUSION: Serum VEGF can be used as a useful and suitable marker to scrutinize the disease activity.

Immunometabolism in the Bladder Cancer Microenvironment.

The initiation and progression of bladder cancer (BC) are dependent on its tumor microenvironment (TME). On the other hand, cancer cells shape and train TME to support their development, respond to treatment and migration in an organism. Immune cells exert key roles in the BC microenvironment and have complex interactions with BC cells. These complicated interplays result in metabolic competition in the TME, leading to nutrient deprivation, acidosis, hypoxia and metabolite accumulation, which impair immune cell function. Recent studies have demonstrated that immune cells functions are closely correlated with their metabolism. Immunometabolism describes the functional metabolic alterations that take place within immune cells and the role of these cells in directing metabolism and immune response in tissues or diseases such as cancer. Some molecules and their metabolites in the TME, including glucose, fatty acids and amino acids, can regulate the phenotype, function and metabolism of immune cells. Hence, here we describe some recent advances in immunometabolism and relate them to BC progression. A profound understanding of the metabolic reprogramming of BC cells and immune cells in the TME will offer novel opportunities for targeted therapies in future.

Clinical relevance and therapeutic potential of IL-38 in immune and non-immune-related disorders

Interleukin-38 (IL-38) is the most recent member of the IL-1 family that acts as a natural inflammatory inhibitor by binding to cognate receptors, particularly the IL-36 receptor. In vitro, animal and human studies on autoimmune, metabolic, cardiovascular and allergic diseases, as well sepsis and respiratory viral infections, have shown that IL-38 exerts an anti-inflammatory activity by modulating the generation and function of inflammatory cytokines (e.g. IL-6, IL-8, IL-17 and IL-36) and regulating dendritic cells, M2 macrophages and regulatory T cells (Tregs). Accordingly, IL-38 may possess therapeutic potential for these types of diseases. IL-38 down-regulates CCR3+ eosinophil cells, CRTH2+ Th2 cells, Th17 cells, and innate lymphoid type 2 cells (ILC2), but up-regulates Tregs, and this has influenced the design of immunotherapeutic strategies based on regulatory cells/cytokines for allergic asthma in future studies. In auto-inflammatory diseases, IL-38 alleviates skin inflammation by regulating γδ T cells and limiting the production of IL-17. Due to its ability to suppress IL-1ß, IL-6 and IL-36, this cytokine could reduce COVID-19 severity, and might be employed as a therapeutic tool. IL-38 may also influence host immunity and/or the components of the cancer microenvironment, and has been shown to improve the outcome of colorectal cancer, and may participate in tumour progression in lung cancer possibly by modulating CD8 tumour infiltrating T cells and PD-L1 expression. In this review, we first briefly present the biological and immunological functions of IL-38, and then discuss the important roles of IL-38 in various types of diseases, and finally highlight its use in therapeutic strategies.

Investigation of TNF-α and IL-6 Levels in the Sera of Non-Melanoma Skin Cancer Patients.

Background: TNF-α and IL-6 are both pleiotropic cytokines playing major roles in cancer-associated cytokine networks. They have previously been investigated for their function in skin malignancies, mostly melanomas, and studies on non-melanoma skin cancer (NMSC) patients are relatively rara. In this study, we aimed to investigate the associations of serum levels of IL-6 and TNF-α with NMSCs and its clinicopathological features. Methods: This cases-control study was carried out to assess the serum levels of TNF-α and IL-6 in 70 NMSC patients, in comparison with 30 healthy individuals, by means of flow cytometric bead-based immuneoassay. Results: Serum levels of both TNF-α and IL-6 were significantly higher in NMSC patients (6.470 vs. 4.355 pg/ml; p = 0.0468, respectively), compared to healthy individuals (3.205 vs. 0.000 pg/ml; p = 0.0126, respectively). In the subgroup analysis, squamous cell carcinomas patients had higher serum levels of IL-6 compared to healthy individuals (3.445 vs. 0.000 pg/ml; p = 0.0432). No other significant differences were observed in the serum levels of these two cytokines among different clinicopathological subgroups of the patients. Conclusion: The increased levels of TNF-α and IL-6 in NMSC patients can be introduced as an epiphenomenon of a complex cancer-induced cytokine cascade.

Elevated IL-37 Serum Levels in Patients with Transitional Cell Carcinoma of Bladder.

BACKGROUND: Interleukin-37 (IL-37) is a recently described cytokine that emerges as a natural inhibitor of inflammatory and immune responses. However, IL-37 has not yet been investigated in bladder cancer, and its biological role is unknown. OBJECTIVE: The purpose of this study was to investigate IL-37 serum levels in patients with bladder cancer and determine whether they were linked to the patients' pathological characteristics. METHODS: IL-37 serum levels were measured using a commercial ELISA kit in 60 patients with transitional cell carcinoma (TCC) of the bladder (mean age: 64.55±12.93) and 50 healthy controls (mean age: 62.94±12.69). Non-parametric tests were used for statistical comparisons, and the Cohen's d effect size was calculated to evaluate the practical and clinical significance of the results. RESULTS: Our findings indicated an increasing trend in IL-37 serum levels in patients with TCC (42.77±3.36 pg/ml) in comparison with controls (40.51±7.32 pg/ml, p=0.09). However, IL-37 serum levels were found to be significantly higher in male patients (44.72±3.81 pg/ml) and patients aged ≥70 (46.92±6.77 pg/ml) in comparison with male controls (29.96±3.30 pg/ml, p=0.026) and controls aged ≥70 (23.62±4.43 pg/ml, p=0.009). In comparison to similar controls, Cohen's d effect size for patients aged ≥70 years was found to be 0.90. CONCLUSION: The findings reveal a higher serum level of IL-37 in patients with TCC, which might be clinically associated with immunosuppression and tumor growth. However, this is a preliminary study, and more research on the biological role of IL-37 and its potential therapeutic effects in bladder cancer is required.

Investigation of IL-17A Serum Levels in Patients with Nonmelanoma Skin Cancer.

BACKGROUND: Role of interleukin 17A (IL-17A) in carcinogenesis and cancer growth is controversial. Although some researches support its antitumor activity, some others suggest that it promotes the growth and development of different types of cancer including skin cancer by activation of STAT3. Although the function of the cytokines such as IL-17A has been extensively studied in various types of cancer, nonmelanoma skin cancer (NMSC) has not received much attention. Therefore, the present study was aimed to investigate the serum levels of IL-17A in NMSC patients. METHODS: This cross-sectional study was performed on 60 patients with basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) as well as 57 age-sex matched healthy individuals as control group. Measurement of IL-17A serum levels in both case and control groups was performed by a commercially reliable sandwich enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: In this study, we observed that IL-17A serum levels in NMSC patients were significantly higher than the control group (P < 0.001). Also, both BCC and SCC patients had higher levels of IL-17A in their sera in comparison to the controls (P=0.001 and P < 0.001, respectively). However, there was no significant difference between SCC and BCC patients regarding serum levels of IL-17A. CONCLUSION: According to our results, it can be concluded that IL-17A may play a role in inducing the growth and progression of NMSC and it can be used as a therapeutic target in these patients in future.

Interleukin-18 gene promoter and serum level in women with ovarian cancer.

IL-18, initially defined as a potent inducer of IFN- gamma production, is a systemic, multifunctional cytokine with both pro-cancerous and anti-cancer activities. The contribution of the IL-18 promoter polymorphisms at positions -607 (C/A) and -137 (G/C) to cancer development has been reported. We sought to examine IL-18 serum level and its polymorphisms in Iranian women with ovarian cancer. Single nucleotide polymorphisms (SNPs) at positions -607 (C/A) and -137 (G/C) were analyzed by allele-specific polymerase chain reaction in 85 women with ovarian cancer and 158 healthy controls. IL-18 serum level was determined using ELISA method. No significant association was found between the allele, genotype, and haplotype distributions of the SNPs and ovarian cancer. Mean IL-18 serum level was significantly higher in patients than in controls (P = 0.008). Comparing IL-18 serum levels with genotypes at positions -607 and -137 revealed no significant difference. No association was also found between IL-18 levels and the disease stage. In conclusion, our results indicate that IL-18 promoter polymorphisms at positions -607 (C/A) and -137 (G/C) appear not to confer susceptibility to ovarian cancer in Iranian population; however, IL-18 serum level increases in ovarian cancer patients.