The effect of Fas/FasL pathway blocking on apoptosis and stemness within breast cancer tumor microenvironment (preclinical study).

Evasion of the immune system is the tumor's key strategy for its maintenance and progression. Thus, targeting the tumor microenvironment (TME) is considered one of the most promising approaches for fighting cancer, where immune cells within the TME play a vital role in immune surveillance and cancer elimination.FasL is one of the most important death ligands expressed by tumor-infiltrating lymphocytes (TILs) and plays a vital role in eliminating Fas-expressing cancer cells via Fas/FasL pathway-induced apoptosis. However, tumor cells can express elevated levels of FasL inducing apoptosis to TILs. Fas/FasL expression is linked to the maintenance of cancer stem cells (CSCs) within the TME, contributing to tumor aggressiveness, metastasis, recurrence, and chemoresistance.This study is considered the first study designed to block the overexpressed FasL on the tumor cells within TME mimicking tissue culture system using rFas molecules and supplementing the Fas enriched tissue culture system with blocked Fas - peripheral blood mononuclear cells PBMCs (using anti-Fas mAb) to protect them from tumor counterattack and augment their ability to induce tumor cell apoptosis and stemness inhibition.A significantly increased level of apoptosis and decreased expression of CD 44 (CSCs marker) was observed within the east tumor tissue culture system enriched with Fas molecules and anti-Fas treated PBMCs and the one enriched with Fas molecules only compared to the breast tumor tissues cultured alone (p < 0.001). Accordingly, we can consider the current study as a promising proposed immunotherapeutic strategy for breast cancer.

Vitamin D Receptor in Breast Cancer Tissues and Its Relation to Estrogen Receptor Alpha (ER-α) Gene Expression and Serum 25-hydroxyvitamin D Levels in Egyptian Breast Cancer Patients: A Case-control Study.

INTRODUCTION: This study aimed to explore the role of vitamin D receptor (VDR) in breast cancer tissues and its relation to serum 25-hydroxyvitamin D [25(OH)D] levels and estrogen receptor alpha (ER-α) gene expression in patients with breast cancer. PATIENTS AND METHODS: Cancerous and normal breast tissues from 40 women with breast cancer were analyzed for quantification of VDR levels and ER-α gene expression. The serum levels of 25(OH)D were measured in patients with breast cancer and controls by radioimmunoassay. RESULTS: Patients with breast cancer had serum levels of 25(OH)D significantly lower than normal control subjects. The levels of VDR and ER-α were significantly higher in breast cancer tissues than in normal breast tissues. The serum levels of 25(OH)D were indirectly and significantly correlated with the tissue levels of both VDR and ER-α gene expression. There was a significant direct correlation between the tissue levels of VDR and ER-α gene expression. The serum 25(OH) D levels, tissue VDR levels, and ER-α gene expression levels were inversely and significantly correlated with breast cancer histopathologic grade. Women with serum 25(OH)D levels ≤ 30 nmol/L, tissue levels of VDR > 5 ng/mL, and tissue levels of ER-α gene expression > 17.7 copies had significantly increased risk for breast cancer incidence. CONCLUSION: Women with low serum 25(OH)D levels, high tissue levels of VDR, and ER-α gene expression had increased risk for breast cancer. VDR are upregulated in breast cancer tissues thus it may be used for target therapy especially in hormone-negative breast cancer.

Adiponectin level changes among Egyptians with gastroesophageal reflux disease.

BACKGROUND AND AIM: Visceral fat is an important endocrine organ that secretes different bioactive substances such as adipocytokines. The aim of this study was to investigate the adiponectin level changes among patients with erosive gastroesophageal reflux disease (GERD)and its consequence on pathogenesis. METHODS: In this study, 150 subjects were selected and divided into four groups: Group І (n = 40) were healthy individuals with an average body mass index and had no gastrointestinal tract symptoms; Group ІІ (n = 50) were patients with mild to moderate erosive esophagitis; Group ІІІ (n = 40) were patients with severe erosive esophagitis; and finally, Group ІV (n = 20) were patients with Barrett's esophagus. Upper gastrointestinal endoscopy was performed for Groups II, III, and IV only, and histopathological assessment was conducted for the suspicious cases of Barrett's esophagus. The measurement of serum adiponectin was performed for all groups using the ELISA test. RESULTS: Our results revealed that the serum level of adiponectin was significantly lower in patients with different grades of GERD as well Barrett's esophagus as compared to healthy controls (P-value < 0.001). Additionally, the serum level of adiponectin was correlated with different grades of GERD as the highest level of the adiponectin was found in the control group (11.05 ± 2.58) followed by mild to moderate GERD (6.39 ± 1.64) and then severe GERD (2.42 ± 1.00); finally, the lowest level was detected in the Barrett's esophagus group (1.99 ± 0.47). Our study showed significant correlation between body mass index, waist circumference, and waist-hip ratio on one hand and serum adiponectin level on the other hand, with a statistically significant difference (P-value < 0.001). The best cut-off value for serum adiponectin was 7.7 (µg/mL), with a sensitivity of 91.8% and specificity of 97.5%. CONCLUSIONS: Low serum adiponectin level appears to be associated with an increased risk of erosive esophagitis, and visceral fat accumulation is related to the impaired secretion of adiponectin, which may have an influence on the pathogenesis of GERD.

Urinary neutrophil gelatinase-associated lipocalin as a marker for disease activity in lupus nephritis.

The neutrophil gelatinase-associated lipocalin (NGAL) has been emerging as a novel biomarker of acute kidney injury while its value in lupus nephritis is uncertain. The aim of this study was to assess urinary NGAL levels as a marker for disease activity in patients with lupus nephritis.This study included 70 systemic lupus erythematosus (SLE) patients; 50 with active lupus nephritis (LN) and 20 without as well as 20 matched controls. The neutrophil gelatinase-associated lipocalin (NGAL) in both serum and urine samples was measured by enzyme-linked immunosorbent assay (ELISA). Patients with active LN received standard treatment then assessed for response as well as the value of urinary NGAL (uNGAL). Our results revealed that, The SLE patients with or without LN had an elevated urinary NGAL as compared to controls (p < 0.000) and the mean of uNGAL was (20.67 ± 5.34),(10.63 ± 3.53),(5.65 ± 2.49) respectively. Furthermore,Urinary NGAL levels in LN patients were significantly higher than those in non-LN patients (P < 0.0001). In the ROC curve analysis , the diagnostic performance of uNGAL for discriminating patients with nephritis from those without nephritis showed that the best cutoff value was 13.66 ng/ml ,sensitivity 92%,specificity 75%,area undercurve (0.959) and (P < 0.0001). Measurement of urinary NGAL levels showed an excellent diagnostic performance for discriminating patients with LN from SLE without nephritis.

The effect of vitamin D deficiency on eradication rates of Helicobacter pylori infection.

BACKGROUND/AIM: Many studies have investigated risk factors other than antibiotic resistance linked to Helicobacter pylori (H. pylori) eradication failure. The aim of this study was to study the effect of serum levels of 25-hydroxy-vitamin D (25[OH]D) on eradication rates of H. pylori infection. METHODS: This study included 150 patients diagnosed with H. pylori gastritis using magnifying narrow-band imaging endoscopy supported by stool antigen test. Serum 25-OH vitamin D levels were measured via the Enzyme-Linked Immune Sorbent assay (ELISA) method before starting eradication therapy of H. pylori infection. All patients were treated with clarithromycin-based triple therapy for 14 days. H. pylori eradication was determined via a stool antigen test performed 4 weeks after the end of therapy. According to the serum level of 25-OH vitamin D levels, the patients were divided into two groups: group I (sufficient) had a vitamin D level of ≥20 ng/mL, while group II (deficient) had a vitamin D level of <20 ng/mL. RESULTS: Our results revealed that eradication was successful in 105 (70%) patients and failed in 45 (30%) patients. The mean 25[OH]D level was significantly lower in the eradication failure group compared to the successful treatment group (14.7 ± 4.5 vs 27.41 ± 7.1; P < 0.001). Furthermore, there were significantly more patients with deficient 25[OH]D levels in the failed treatment group, 30 (66.6%), compared to the successful group, 10 (9.5%) (P < 0.001). CONCLUSIONS: Our results demonstrated that 25-OH vitamin D deficiency may be considered a risk factor related to eradication failure of H. pylori infection. In addition, a further randomized trial to evaluate the effect of vitamin D supplementation in H. pylori eradication is mandatory.

Interleukin (Il)-12, Il-5 and total IgE in hepatosplenic schistosomiasis with or without asthma.

There are a number of similarities between protective immune responses against schistosomiasis and asthma. Both are associated with elevated concentrations of IgE and eosinophilia. Chronic schistosomiasis is liked to Th1 like response with involvement of pro-inflammatory cytokines in schistosomal hepatosplenic disease process resulting in low level of IL-5. Meanwhile, association with asthma could modulate the immune response with shift to Th2 side resulting in marked elevation of IL-5 and eosinophilia. This work evaluated the levels of serum IgE, IL-5 and IL-12 in Schistosoma mansoni-infected asthmatic patients. A total of 100 subjects selected from Al-Azhar University's Hospitals were divided into three groups GI: 50 patients with hepatosplenic schistosomiasis associated with asthma. GII: 25 patients with hepatosplenic schistosomiasis without apparent asthma. GIII: 25 patients with neither bilharzial liver cirrhosis nor asthma as control group. All patients were subjected to full history taking and clinical examination, pulmonary function tests, total serum IgE, bilharzial antibody titre, stool and urine examination for parasites, liver function tests and serum IL-5 and IL-12. The results showed very high level of the total serum IgE in GI and GII compared to GIII. There was high significant difference in peripheral blood eosinophil%. GI & GII gave highest levels, IL-5 was elevated in GI, but low GII, I-12 was high in GII than GI.