Phenotypic Analysis of Circulating Myeloid Derived Suppressor Cells and Their Subpopulations in Egyptian Females with Breast Cancer: A Single-Centre Case-Control Study.

BACKGROUND: Myeloid-derived suppressor cells (MDSC) are immature myeloid cells with suppressive function that has been thoroughly documented in the setting of cancer. Our purpose was to evaluate levels of MDSC and their subsets in a cohort of Egyptian patients with breast cancer. METHODS: Evaluation of peripheral blood total MDSC and its subset was done using multicolor flowcytometry in 30 malignant, 10 benign breast tumor patients and 10 healthy control females. RESULTS: BC patients had higher total MDSC levels compared to controls (p= 0.01) particularly the Monocytic MDSC (M-MDSC) and abnormal MDSC subsets (p = 0.001 and p <0.001, respectively). A tumor size > 2 cm exhibited significantly higher granulocytic MDSCs (G-MDSCs) compared to tumor size < 2 cm (p= 0.02) whereas abnormal MDSCs were significantly higher in patients with a tumor size < 2 cm (p = 0.037). CONCLUSION: MDSC and its subsets can be used as a prognostic marker of tumor size as well as a potential targets for treatment in breast cancer patients.

Assessment of donor specific IgG Anti-HLA subclasses before and after kidney transplantation in Upper Egypt: A Single Center Study.

Donor specific antibodies (DSAs) are known as the leading cause of antibody mediated rejection (AMR), graft loss in kidney transplant (KT) recipients. DSAs characteristics, as immunoglobulin (Ig) classes, subclasses, and strength, are important to assess the immunological risk, early prediction of AMR, and therefor proper management. This longitudinal, case control study included 32 KT recipients at Assiut University Urology Hospital and 10 age and sex matched normal subjects as the control group. Total IgG, its subclasses and anti-human leukocyte antigen (anti-HLA) panel reactive antibody (PRA) were detected pre-transplantation (pre-TX), at 6-12- and 24-36-months post-TX. Rejection occurred in 4 recipients, 3 of them had high total IgG, IgG1 and/or IgG3. IgG2 and IgG4 were normal in all recipients. There were preformed anti-DSAs antibodies in 3/32 recipients (9.4%). Of these, two recipients became negative with no rejection occurred. The third recipient had high post-TX mean fluorescence intensity (MFI) and AMR occurred. The pre-TX PRA was negative in 29/32 recipients (90.6%). The PRA was negative in 8/29 recipients (27.6%) and the remaining 21/29 recipients (72.4%) developed de novo DSAs post-TX (MFI < 3000->10000). Rejection occurred with both low and high MFI. In 11 recipients, anti-HLA class I and II were not different between pre-TX, 3-6- and 24-36 months post-TX with no rejection occurred. The frequency and median levels of total IgG, IgG1 and IgG3 were increased in all recipients 24-36 months post-TX when compared with their levels pre-TX and 6-12 months post-TX in the 11 recipients and with the control group. The graft survival time significantly decreased in recipients with positive post-TX class I PRA. In conclusion, preformed DSAs may persist post-TX or turn negative. De novo DSAs developed post-TX even in non-sensitized recipients. Serum total IgG, IgG1 and IgG3 frequency increase 2-3 years post-TX.

Different vitiligo characteristics as predictors of increased risk of metabolic syndrome and insulin resistance: A case-control study.

BACKGROUND: Autoimmune and metabolic disturbances have been reported in association with vitiligo, highlighting possible systemic associations that should be considered. AIMS: To assess the possible association of metabolic syndrome (MetS) as well as insulin resistance (IR) with vitiligo in different age groups. METHODS: This case-control study included 142 patients with vitiligo aging ≥ 6 years and 142 age- and sex-matched controls. Participants were assessed for MetS using the International Diabetes Federation (IDF) criteria in addition to IR via homeostasis model assessment of IR (HOMA-IR). The study was registered at Clinical Trials.gov, Identifier: NCT03622320, on August 9, 2018. RESULTS: As per the IDF criteria, patients with vitiligo showed significantly more frequent association with high fasting plasma glucose levels, high blood pressure readings, central obesity, dyslipidemia, and MetS than controls (p = 0.020, p = 0.034, p = 0.014, p < 0.001, and p = 0.002, respectively). Moreover, patients with vitiligo have significantly higher levels of fasting insulin and HOMA-IR (p ≤ 0.001). Results obtained from patients with vitiligo and controls with coexistent MetS/IR demonstrated vitiligo as a risk factor for both MetS and IR. Univariate and multivariate logistic regression highlighted that older age was the significant independent predictor for MetS and IR. CONCLUSION: Patients with vitiligo showed a significantly higher incidence of MetS than controls. Vitiligo per se can be considered a risk factor for MetS and IR. Therefore, regular follow-up and early metabolic derangement diagnoses are mandatory.

Role of endoscopic ultrasound and cyst fluid tumor markers in diagnosis of pancreatic cystic lesions.

BACKGROUND: Pancreatic cystic lesions (PCLs) are common in clinical practice. The accurate classification and diagnosis of these lesions are crucial to avoid unnecessary treatment of benign lesions and missed opportunities for early treatment of potentially malignant lesions. AIM: To evaluate the role of cyst fluid analysis of different tumor markers such as cancer antigens [e.g., cancer antigen (CA)19-9, CA72-4], carcinoembryonic antigen (CEA), serine protease inhibitor Kazal-type 1 (SPINK1), interleukin 1 beta (IL1-ß), vascular endothelial growth factor A (VEGF-A), and prostaglandin E2 (PGE2)], amylase, and mucin stain in diagnosing pancreatic cysts and differentiating malignant from benign lesions. METHODS: This study included 76 patients diagnosed with PCLs using different imaging modalities. All patients underwent endoscopic ultrasound (EUS) and EUS-fine needle aspiration (EUS-FNA) for characterization and sampling of different PCLs. RESULTS: The mean age of studied patients was 47.4 ± 11.4 years, with a slight female predominance (59.2%). Mucin stain showed high statistical significance in predicting malignancy with a sensitivity of 87.1% and specificity of 95.56%. It also showed a positive predictive value and negative predictive value of 93.1% and 91.49%, respectively (P < 0.001). We found that positive mucin stain, cyst fluid glucose, SPINK1, amylase, and CEA levels had high statistical significance (P < 0.0001). In contrast, IL-1ß, CA 72-4, VEGF-A, VEGFR2, and PGE2 did not show any statistical significance. Univariate regression analysis for prediction of malignancy in PCLs showed a statistically significant positive correlation with mural nodules, lymph nodes, cyst diameter, mucin stain, and cyst fluid CEA. Meanwhile, logistic multivariable regression analysis proved that mural nodules, mucin stain, and SPINK1 were independent predictors of malignancy in cystic pancreatic lesions. CONCLUSION: EUS examination of cyst morphology with cytopathological analysis and cyst fluid analysis could improve the differentiation between malignant and benign pancreatic cysts. Also, CEA, glucose, and SPINK1 could be used as promising markers to predict malignant pancreatic cysts.

Value of pancreatic cyst fluid SPINK1 and glucose in differentiating potentially malignant cysts from those of benign nature: A prospective cohort study.

Background: Diagnosis of malignant pancreatic cystic lesions (PCLs) is challenging as there is no investigation that offers both high diagnostic sensitivity and specificity for a definite diagnosis. Accurate diagnosis of cyst type is vital in order to not miss opportunities for early treatment of potentially malignant lesions and to avoid unnecessary surgeries. Serine protease inhibitor Kazal type I (SPINK1) and glucose are promising cyst fluid markers for differentiation of mucinous from non-mucinous cysts. We aim to validate the value of SPINK1 and glucose in detecting potentially malignant PCLs. Methods: A prospective study was conducted on 80 patients presenting with PCLs. Endoscopic ultrasound (EUS) evaluation of detailed cyst morphology and EUS with fine needle aspiration (FNA) were done. Fluid analysis for carcinoembryonic antigen (CEA), glucose and SPINK1 and cytopathology were done. We compared these data with the final diagnosis based on cytopathological and postoperative histopathological examination. Results: Cyst fluid SPINK1 was significantly higher in malignant or potentially malignant cysts compared to benign cysts (0.91 vs 0.47 ng/ml; P = 0.001). Also, glucose was significantly lower in malignant or potentially malignant cysts compared to benign cysts (21.5 vs 68.5 mg/dl; P = 0.0001). Glucose and SPINK1 had the best sensitivity and specificity for differentiating mucinous from non-mucinous cysts with 84.78% and 73.53% (AUC 0.76; 95% CI [0.65-0.88]; cutoff value = 42 mg/dl), and 70.59% and 65.22% (AUC 0.72; 95% CI [0.64-0.86]; cutoff value = 0.58 ug/L) respectively. CEA level >192 ng/ml, high SPINK1 level and lymph node enlargement were the independent predictors of malignant cysts. Conclusion: Cyst fluid SPINK1 and glucose are promising diagnostic markers for the diagnosis of potentially malignant PCLs.

The Role of Interleukin 1 Beta in Differentiating Malignant from Benign Pancreatic Cysts.

Background and Aim: The frequency of detection of pancreatic cystic lesions (PCLs) in magnetic resonance imaging performed for reasons unrelated to the pancreas reaches up to 13.5%. The aim of this study was to evaluate the role of cyst fluid interleukin 1 beta (IL1ß) and different endoscopic ultrasound (EUS) features in differentiating premalignant/malignant from benign pancreatic cysts. In addition, to evaluate the role of pancreatic cyst fluid carcinoembryonic antigen (CEA) in differentiating mucinous from nonmucinous pancreatic cysts. Methods: This study was conducted on 73 patients with PCLs. EUS-guided fine-needle aspiration (EUS-FNA) was performed on all patients. Estimation of IL1ß and CEA levels in aspirated specimens were carried out. Results: Pancreatic cyst fluid IL1ß level could not differentiate between premalignant/malignant and benign pancreatic cysts. At a cutoff value of 19.81 ng/mL pancreatic cyst fluid CEA has 64.3% sensitivity and 84.4% specificity in differentiating mucinous from nonmucinous pancreatic cyst. EUS can differentiate between premalignant/malignant pancreatic cysts and benign cysts with a sensitivity of 66.7%, specificity of 69.2% Conclusions: Pancreatic cyst fluid IL1ß level cannot differentiate between premalignant/malignant and benign pancreatic cysts. CEA level can help in differentiation between mucinous and nonmucinous cysts. EUS can be useful in differentiation between premalignant/malignant pancreatic cysts and benign cysts.

Possible enigmatic link between serum leptin and vitiligo with its metabolic derangements: A comparative controlled study.

OBJECTIVE: Serum leptin, an adipocytokine of interleukin-6 family, has been linked to vitiligo-associated metabolic derangements. Additionally, it has been proposed as an inflammatory mediator with possible influence on vitiligo pathogenesis. This study aimed at assessing serum leptin in vitiligo patients compared to controls and whether different vitiligo characteristics have an influence on serum leptin levels. METHODS: In this hospital-based, cross-sectional case-control study, 70 vitiligo (35 segmental vitiligo (SV) and 35 Non-segmental vitiligo (NSV)) and 70 age- and sex-matched controls were assessed for different anthropometric measurements including waist circumference (WC), index of central obesity (ICO), and body mass index (BMI) as well as serum leptin levels. RESULTS: Central obesity as per ICO showed no significant difference between patients and controls. Additionally, patients of SV and NSV collectively showed significant higher incidence of +ve serum leptin than their controls (41.4% vs. 22.9%%, P: 0.019). Mere presence of vitiligo and ICO >0.5 were highlighted as independent predictors of +ve serum leptin (P: 0.009 and <0.001, respectively). LIMITATION: Inability to determine a cause/effect relationship based on a cross-sectional study. Larger scale studies are needed to affirm our findings. CONCLUSION: Mere presence of vitiligo being an independent predictor for high serum leptin could be either a contributor to pathogenesis of vitiligo or a sequel to accumulating evidence of metabolic nature of vitiligo. This is likely to influence the investigative panel and treatment protocol for vitiligo patients.

Obinutuzumab in Kidney Transplantation: Effect on B-cell Counts and Crossmatch Tests.

BACKGROUND: Resistance to the action of rituximab (RTX) has been documented in several diseases. More recently, obinutuzumab (OBZ) has shown promise where RTX has failed in oncology and lupus nephritis. Unlike RTX, OBZ is a weak activator of complement, which may avoid the false-positive complement-dependent cytotoxicity (CDC) crossmatch tests after RTX infusions. METHODS: The aim of this study was to explore the effect of OBZ on B-cell depletion in kidney-transplant candidates and its impact on crossmatch test results. We included 12 patients, who were either highly sensitized kidney-transplant candidates or kidney-transplant recipients presenting with antibody-mediated rejection. Six received OBZ, and 6 received RTX. CD-19 counts, flow cytometry, and CDC crossmatch tests were run immediately before and at 2 wk after drug infusion. RESULTS: OBZ reduced CD-19 counts: median reduction was 98%. B-cell CDC crossmatch test results became positive following RTX infusion but were not affected by OBZ infusion. CONCLUSIONS: OBZ effectively depleted B-cell counts in sensitized kidney-transplant candidates and, unlike RTX, had no effect on CDC crossmatch results.

Donor cell microchimerism in kidney transplantation: Implications for graft function.

Given the uncertainty regarding the relationship between donor cells at microchimeric levels and its influence on graft function and clinical outcome, we explored the extent and importance of donor microchimerism in kidney transplantation. Twenty patients with chronic kidney disease who had received allografts from living donors were studied. We examined peripheral whole blood samples from the recipients one month after the transplant, applying mitochondrial DNA variant-specific polymerase chain reaction (PCR) to identify and quantify donor cells in relation to allograft function and survival during three years of follow-up. Higher quantities of donor-derived cell microchimerism in the peripheral blood correlated with better graft function in the early postoperative period at 1 month (R2  = .536, p = .001) and predicted improved graft function 1 year following the transplant (R2  = .430, p = .008). Furthermore, early post-transplant quantities of donor cell microchimerism were an important predictor of improved kidney function 3 years after transplantation (R2  = .397, p = .021). However, donor cell microchimerism failed to predict patient and graft survival after 3 years (odds ratio = 0.536, p = .860). Our findings suggest that donor cell microchimerism plays an immunoregulatory role in kidney transplantation and contributes to donor-specific immune hypo-responsiveness and graft acceptance.

Regenerative potential of cultured gingival fibroblasts in treatment of periodontal intrabony defects (randomized clinical and biochemical trial).

BACKGROUND: Defective cellular elements constitute an important challenge to achieve predictable periodontal regeneration. In an attempt to improve the cellularity of periodontal defects, gingival fibroblasts were implanted without their associated extracellular elements in periodontal defects to expose them to periodontal tissue mediators. In order to investigate the regenerative potential of gingival fibroblasts translocated into periodontal defects, the present study was designed to clinically and biochemically investigate the use of gingival fibroblasts (GF) and their associated mesenchymal stem cells (GMSC) in the treatment of intrabony periodontal defects. METHODS: A total of 20 subjects were randomly divided into two groups (n = 20). Group I: ten patients were included with ten intrabony periodontal defects that received ß-calcium triphosphate (ß-TCP) followed by collagen membrane defect coverage, while group II: (10 patients) ten periodontal defects received cultured gingival fibroblasts (GF) on the ß-TCP scaffold and covered by a collagen membrane. The clinical evaluation was carried out at the beginning and at 6 months. Gingival crevicular fluid (GCF) samples were collected directly from the test sites for the quantitative measurement of PDGF-BB and BMP-2 using the ELISA kit at 1, 7, 14, and 21 days after surgery. RESULTS: Group II reported a significantly greater reduction in vertical pocket depth (VPD) and CAL gain compared with group I after 6 months. Radiographic bone gain was statistically higher in group II compared with group I. A significantly higher concentration of PDGF-BB was observed in group II on days 1, 3, and 7 compared with group I. CONCLUSIONS: Translocation of gingival fibroblasts from gingival tissue to periodontal defects could be a promising option that increases cellular elements with regeneration potential. The concept of total isolation of gingival fibroblasts using occlusive membranes must be re-evaluated.

Evaluation of the S100 protein A12 as a biomarker of neonatal sepsis.

Introduction: Sepsis has a grave impact on neonatal morbidity and mortality. Proper timely diagnosis and a subsequently tailored management are crucial to improving neonatal outcome and survival. New diagnostic methods are needed and much effort is directed to this objective. In this work, we aimed to evaluate S100A12 protein as a biomarker of neonatal sepsis.Materials and methods: In this prospective single-center study, 118 preterm and term neonates were enrolled and assigned to four groups: controls, infants with no infection, infants with probable infection and infants with proven infection. Clinical and routine laboratory data, the serum levels of S100A12 and additional cytokines (interleukin (IL)-1ß, IL-2, IL-6, IL-17A, IL-18, IL-22, IL-10, and interferon (IFN)-γ) were assessed. Using stepwise multivariate logistic regression analysis, S100A12 protein was evaluated as a biomarker of neonatal infection.Results: Significant differences of the parameters of complete blood count and level of C-reactive protein were documented between the study/the four groups. The studied marker S100A12, as well as IL-6 and IL-10, were highly significant (p < .001) between infected and control groups. S100A12 had a sensitivity of 96.8% and a specificity of 93.3%. Even after adjusting for the confounding factors sex, body weight, gestational age, mode of delivery, number of pregnancies, premature rupture of membranes, and preeclampsia S100A12 remained significant between the infected and control groups.Conclusions: S100A12 may be considered as a new biomarker of neonatal sepsis.

Urinary podocyte-associated mRNA profile in Egyptian patients with diabetic nephropathy.

INTRODUCTION: Podocyte injury and subsequent excretion in urine play a crucial role in the pathogenesis and progression of diabetic nephropathy (DN). Quantification of messenger RNA expression in urinary sediment by real-time PCR is emerging as a noninvasive method of screening DN-associated biomarkers. We aimed to study the expression of podocyte-associated genes in urinary sediment and their relation to disease severity in type 2 diabetic Egyptian patients with diabetic nephropathy. METHOD: ology: Sixty patients with type 2 diabetes mellitus were recruited in addition to twenty non diabetic healthy volunteers. Relative mRNA abundance of nephrin, podocalyxin, and podocin were quantified, and correlations between target mRNAs and clinical parameters were examined. RESULTS: The urinary mRNA levels of all genes studied were significantly higher in diabetics compared with controls (p < 0.001), and mRNA levels increased with DN progression. Urinary mRNA levels of all target genes positively correlated with both UAE and HbA1c. The expression of nephrin, podocalyxin, and podocin mRNA correlated with serum creatinine {(r = 0.397, p value = 0.002), (r = 0.431, p value = 0.001), (r = 0.433, p value = 0.001) respectively}. CONCLUSION: The urinary mRNA profiles of nephrin, podocalyxin, and podocin were found to increase with the progression of DN, which suggested that quantification of podocyte-associated molecules will be useful biomarkers of DN.

Synthesis and Characterization of Novel BMI1 Inhibitors Targeting Cellular Self-Renewal in Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) represents one of the most lethal cancers worldwide due to therapy resistance and disease recurrence. Tumor relapse following treatment could be driven by the persistence of liver cancer stem-like cells (CSCs). The protein BMI1 is a member of the polycomb epigenetic factors governing cellular self-renewal, proliferation, and stemness maintenance. BMI1 expression also correlates with poor patient survival in various cancer types. OBJECTIVE: We aimed to elucidate the extent to which BMI1 can be used as a potential therapeutic target for CSC eradication in HCC. METHODS: We have recently participated in characterizing the first known pharmacological small molecule inhibitor of BMI1. Here, we synthesized a panel of novel BMI1 inhibitors and examined their ability to alter cellular growth and eliminate cancer progenitor/stem-like cells in HCC with different p53 backgrounds. RESULTS: Among various molecules examined, RU-A1 particularly downregulated BMI1 expression, impaired cell viability, reduced cell migration, and sensitized HCC cells to 5-fluorouracil (5-FU) in vitro. Notably, long-term analysis of HCC survival showed that, unlike chemotherapy, RU-A1 effectively reduced CSC content, even as monotherapy. BMI1 inhibition with RU-A1 diminished the number of stem-like cells in vitro more efficiently than the model compound C-209, as demonstrated by clonogenic assays and impairment of CSC marker expression. Furthermore, xenograft assays in zebrafish showed that RU-A1 abrogated tumor growth in vivo. CONCLUSIONS: This study demonstrates the ability to identify agents with the propensity for targeting CSCs in HCC that could be explored as novel treatments in the clinical setting.

Therapeutic efficacy of human umbilical cord mesenchymal stem cells transplantation against renal ischemia/reperfusion injury in rats.

BACKGROUND: Acute kidney injury (AKI) is a common clinical problem raising the urgent needs to develop new strategies for treatment. The present study investigated the therapeutic potential of human umbilical cord - mesenchymal stem cells (HUC-MSCs) transplantation against renal ischemia/reperfusion injury (IRI) in rats. METHODS: Twenty four male Wistar rats were assigned into two main groups, sham group (control group) and I/R group. I/R group was injected in the tail vein with either phosphate buffer saline (PBS) or HUC-MSCs. RESULTS: The HUC-MSCs improved kidney injury induced by I/R as demonstrated by enhancement of the kidney function via decreasing serum levels of creatinine, urea and uric acid. The therapeutic efficacy of HUC-MSCs were found to be mediated through anti-oxidant activity as indicated by significant reduction in total malondialdehyde (MDA) and significant increment in the levels of reduced glutathione (GSH), catalase (CAT) and glutathione-S-transferase (GST). CONCLUSION: The present work suggests that HUC-MSCs may be an effective therapeutic agent against renal IRI. The recorded data showed improvement of renal functions and urine albumin in HUC-MSCs than IRI group with positive antioxidant efficacy of HUC-MSCs through scavenging free radicals and supporting the antioxidant enzymes.

Erratum to: Umbilical cord mesenchymal stem cells derived extracellular vesicles can safely ameliorate the progression of chronic kidney diseases.

[This corrects the article DOI: 10.1186/s40824-016-0068-0.].

The Effect of Monophosphoryl Lipid A on Maturation of DCs from Patients with Acute Myeloid Leukaemia.

BACKGROUND: Generation of monocyte-derived dendritic cells (MDDC) is induced in the presence of GM-CSF and IL-4, and a maturation stimulus is added to the monocyte culture to obtain mature Dendritic Cells (DCs) suitable for therapy. TNF-α is the most common cytokine used for activating DCs and generating mature MDDC either alone or in combination with other cytokines. OBJECTIVE: To compare effects of traditional cytokine cocktail (TNF-α + IL-1ß) versus TLR4-agonist monophosphoryl lipid A on the viability, phenotype, cytokine profile and functionality of MDDC. METHODS: The study included 32 individuals; twenty Acute Myeloid Leukaemia (AML) cases in complete remission and 12 healthy volunteers. They were divided into 3 groups: Group 1: control group: 12 subjects to measure the baseline levels of all markers in the monocytic preparation. Group 2: cytokine cocktail (TNF-α) group, which included 10 AML subjects. Group 3: MPLA group which included 10 AML subjects. RESULTS: TNF-α group showed higher expression of CD83 than MPLA group indicating higher capacity to induce DC maturation but both were similar in CD86, CCR7 and IL-10 expression. Preparation of dendritic cells from AML cases in remission and loading them with tumor peptides was successful. CONCLUSION: MPLA effect in DC maturation is comparable with traditional DC maturation cocktail.

Umbilical cord mesenchymal stem cells derived extracellular vesicles can safely ameliorate the progression of chronic kidney diseases.

BACKGROUND: Bio-products from stem/progenitor cells, such as extracellular vesicles, are likely a new promising approach for reprogramming resident cells in both acute and chronic kidney disease. Forty CKD patients stage III and IV (eGFR 15-60 mg/ml) have been divided into two groups; twenty patients as treatment group "A" and twenty patients as a matching placebo group "B". Two doses of MSC-derived extracellular vesicles had been administered to patients of group "A". Blood urea, serum creatinine, urinary albumin creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) have been used to assess kidney functions and TNF-α, TGF-ß1 and IL-10 have been used to assess the amelioration of the inflammatory immune activity. RESULTS: Participants in group A exhibited significant improvement of eGFR, serum creatinine level, blood urea and UACR. Patients of the treatment group "A" also exhibited significant increase in plasma levels of TGF-ß1, and IL-10 and significant decrease in plasma levels of TNF-α. Participants of the control group B did not show significant improvement in any of the previously mentioned parameters at any time point of the study period. CONCLUSION: Administration of cell-free cord-blood mesenchymal stem cells derived extracellular vesicles (CF-CB-MSCs-EVs) is safe and can ameliorate the inflammatory immune reaction and improve the overall kidney function in grade III-IV CKD patients.

Human leukocyte antigen-DRB1 polymorphism in childhood acute lymphoblastic leukemia.

Similar to autoimmune diseases, there are clear associations between resistance or susceptibility to cancer and the classic human leukocyte antigen (HLA) profile of an individual. HLA-associated susceptibility to childhood acute lymphoblastic leukemia (ALL) may provide clues to leukemogenesis in general and to the role of other risk factors. The present study aimed to determine the association between the HLA-DRB1 genotype and susceptibility to ALL in children and to assess the prognostic value of HLA-DRB1 alleles in these patients. This study included 50 ALL patients who were consecutively admitted to the Pediatric Oncology Unit of Zagazig University Hospital and 50 gender-matched healthy volunteers as a control group. The patients were subjected to full clinical history, thorough clinical examination and routine laboratory investigations. Molecular HLA-DRB1 typing for patients and controls using the reverse sequence-specific oligonucleotide probe technique was performed. HLA-DRB1*04 allele frequency was significantly higher in female patients compared to that in female controls (P=0.03) and in patients aged <10 years compared to those aged ≥10 years at the time of diagnosis (P=0.01). HLA-DRB1*11 allele frequency was significantly higher in high-risk compared to standard-risk patients (P=0.01) and in refractory patients compared to those who achieved remission (P=0.02). In conclusion, the HLA-DRB1*04 allele appears to be a female-specific susceptibility factor for the acquisition of childhood ALL and it may affect the age of onset of ALL. In addition, the HLA-DRB1*11 allele may be of prognostic significance in childhood ALL. However, further larger studies are required to support the conclusions drawn from this study.

Immunotherapy by autologous dendritic cell vaccine in patients with advanced HCC.

BACKGROUND: Dendritic cells (DCs) could be used as potential cellular adjuvant for the production of specific tumor vaccines. OBJECTIVES: Our study was aimed to evaluate the safety and efficacy of autologous pulsed DC vaccine in advanced hepatocellular carcinoma (HCC) patients in comparison with supportive treatment. METHODS: Thirty patients with advanced HCC not suitable for radical or loco-regional therapies were enrolled. Patients were divided into 2 groups, group I consisted of 15 patients received I.D vaccination with mature autologous DCs pulsed ex vivo with a liver tumor cell line lysate. Group II (control group, no. 15) received supportive treatment. One hundred and 4 ml of venous blood were obtained from each patient to generate DCs. DCs were identified by CD80, CD83, CD86 and HLA-DR expressions using flow cytometry. Follow up at 3, and 6 months post injection by clinical, radiological and laboratory assessment was done. RESULTS: Improvement in overall survival was observed. Partial radiological response was obtained in 2 patients (13.3 %), stable course in 9 patients (60 %) and 4 patients (26.7 %) showed progressive disease (died at 4 months post-injection). Both CD8(+) T cells and serum interferon gamma were elevated after DCs injection. CONCLUSION: Autologous DC vaccination in advanced HCC patients is safe and well tolerated.