Sinopharm's BBIBP-CorV Vaccine and ChAdOx1 nCoV-19 Vaccine Are Associated with a Comparable Immune Response against SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) has affected millions of people worldwide. During the early stages of vaccination in Egypt, the ChAdOx1 nCoV-19 and BBIBP-CorV vaccines were the most distributed. The aim of this study was to compare the immune responses and short-term efficacies of these two vaccines. We recruited adults who received two doses of either vaccine. Samples were collected after the first dose of ChAdOx1 nCoV-1 and after the second dose of both vaccines. Antibodies against SARS-CoV-2 antigens were measured using LABScreen™ COVID Plus kits, and cell-mediated immune responses were assessed using flow cytometry. Of the 109 recruited subjects, 60 (55%) received the ChAdOx1 nCoV-19 vaccine, and the remainder received the BBIBP-CorV vaccine. The total antibody level did not significantly differ between the two groups. The level of the anti-spike subunit 2 (S2) antibody was significantly higher in the ChAdOx1 nCoV-19 group. The percentages of both total T cells and B cells were unaffected by the type of vaccination. However, the ChAdOx1 nCoV-1 vaccine was significantly associated with a higher percentage of CD8+ cells. The vaccines did not significantly differ in the number or severity of infections postvaccination. None of the participants were admitted to the hospital or died of COVID-19 infection. In conclusion, the BBIBP-CorV vaccine is associated with an immune response and protection against infection that is comparable to that of the ChAdOx1 nCoV-1 vaccine. Follow-up is needed to study the long-term protective effects of both vaccines. Inactivated vaccines are easier to manufacture in developing countries and their limited side effects may lead to better economic benefits by limiting the number of absences from work.

T-lymphocytes Expression of Toll-like Receptors 2 and 4 in Acute Myeloid Leukemia Patients with Invasive Fungal Infections.

Background: Invasive fungal infections (IFIs) are important cause of mortality in acute myeloid leukemia (AML) patients on treatment with intensive induction chemotherapy. Toll-like receptors, mainly Toll-like receptors 2 and 4 (TLR2 and TLR4), play a considerable role in the host defense against microorganisms. The involvement of TLR signaling in modulation of innate immune response is extensively discussed, but the TLR expressions profiling on adaptive immune cells are not specified. Also, the expressions of TLRs and their association with the occurrence of IFIs in patients with AML are not studied. So, the novel aim of this study was to investigate the associations between the T-lymphocyte expression of TLR2 and TLR4 and the occurrence of IFIs in AML patients treated with intensive induction chemotherapy. Materials and Methods: One hundred twenty two newly diagnosed AML patients were evaluated. The laboratory diagnostic techniques for IFIs include culture, microscopic examination, histopathology, galactomannan assay and PCR. The expressions of TLR2 and TLR4 were analyzed by flow cytometry. The Control group included 20 age and sex-matched individuals. Results: There was a significant increase in the expression of TLR4 in AML patients with IFI compared to healthy controls (p = 0.001). TLR2 and TLR4 expressions increased significantly in AML patients with mixed fungal and bacterial infection compared to healthy controls (p= 0.002 and p=0.001, respectively). Conclusion: TLRs expressions could be important biological markers for the occurrence of IFI in non-M3 AML patients after intensive induction chemotherapy.

HLA-B*15 predicts survival in Egyptian patients with COVID-19.

Genetic differences among individuals could affect the clinical presentations and outcomes of COVID-19. Human Leukocyte Antigens are associated with COVID-19 susceptibility, severity, and prognosis. This study aimed to identify HLA-B and -C genotypes among 69 Egyptian patients with COVID-19 and correlate them with disease outcomes and other clinical and laboratory data. HLA-B and -C typing was performed using Luminex-based HLA typing kits. Forty patients (58%) had severe COVID-19; 55% of these patients died, without reported mortality in the moderate group. The alleles associated with severe COVID-19 were HLA-B*41, -B*42, -C*16, and -C*17, whereas HLA-B*15, -C*7, and -C*12 were significantly associated with protection against mortality. Regression analysis showed that HLA-B*15 was the only allele associated with predicted protection against mortality, where the likelihood of survival increased with HLA-B*15 (P < 0.001). Patient survival was less likely to occur with higher total leukocytic count, ferritin, and creatinine levels. This study provides interesting insights into the association between HLA class I alleles and protection from or severity of COVID-19 through immune response modulation. This is the first study to investigate this relationship in Egyptian patients. More studies are needed to understand how HLA class I alleles interact and affect Cytotoxic T lymphocytes and natural killer cell function.

Efficacy of adipose-derived stromal vascular fraction cells in the management of chronic ulcers: a randomized clinical trial.

Background: Cell therapy is a promising method for improving healing in chronic ulcers through delivery of isolated adipose-derived stromal vascular fraction. Objectives: This study investigates the autologous stem cell yield of adipose tissue and its efficacy in chronic ulcers compared with conventional methods. Methods: This study was a randomized controlled trial. After the study design and protocol were established and ethical committee approval was obtained, we enrolled 100 patients divided into study and control groups. In the study group, we performed debridement and autologous stem cell injection every 3 weeks. The control group was treated with debridement and conventional dressing. Assessments included clinical and histological parameters. Results: The study group showed improved healing. Conclusion: Using autologous adipose-derived stromal vascular fraction cells is an effective treatment method for chronic ulcers. This study was registered on the Pan-African Clinical Trial Registry and the number of the registry was PACTR201709002519185.

Relationship of transitional regulatory B and regulatory T cells and immunosuppressive drug doses in stable renal transplant recipients.

OBJECTIVES: Regulatory B cells (Bregs) and T cells (Tregs) are thought to be involved in the regulation of graft acceptance in renal transplant recipients. However, mechanisms that affect Breg differentiation and interaction with Tregs are rather unclear. METHODS: Using eight-color-fluorescence flow cytometry, Tregs and CD19+ CD24hiCD38hi Bregs were analyzed in whole blood samples of 80 stable kidney transplant recipients, 20 end-stage renal disease (ESRD) patients and 32 healthy controls (HC). In addition, differentiation of Bregs and Tregs was studied in different micromilieus using cocultures with strongly enriched B-lymphocytes and autologous peripheral blood mononuclear cells stimulated with CpG and phytohemagglutinin. RESULTS: Bregs were higher in HC than in ESRD patients and lowest in transplant recipients. Bregs were higher early as compared to late posttransplant. Posttransplant, high Bregs were associated with higher glomerular filtration rate (GFR) and lower C-reactive protein (CRP). Higher doses and blood levels of ciclosporine, tacrolimus, and mycophenolate mofetil as well as higher doses of steroids were not associated with low Bregs. In contrast, most Treg subsets were lower when blood levels of ciclosporine, tacrolimus, and mycophenolate mofetil were higher. Tregs were not associated with Bregs, GFR, CRP plasma levels, and occurrence of rejection or infection. In vitro, differentiation of Bregs was strongly dependent on T cell support and was blocked by excessive or lacking T-cell help. Tregs were not associated with Breg numbers in vitro. CONCLUSION: Bregs appear to be insensitive to high doses of posttransplant immunosuppressive drugs. The protracted Breg decrease posttransplant might be caused by impaired T cell support attributable to immunosuppressive drugs.

Higher CD19+CD25+ Bregs are independently associated with better graft function in renal transplant recipients.

BACKGROUND: The Identification of B cell subsets with regulatory functions might open the way to new therapeutic strategies in the field of transplantation, which aim to reduce the dose of immunosuppressive drugs and prolong the graft survival. CD25 was proposed as a marker of a B-cell subset with an immunosuppressive action termed Bregs. The effect of CD19 + CD25 + Bregs on graft function in renal transplant recipients has not yet been elucidated. We investigated a potential impact of CD19 + CD25 + Bregs on renal graft function as well as a possible interaction of CD19 + CD25 + Bregs with peripheral Tregs in healthy controls, end-stage kidney disease patients (ESKD), and renal transplant recipients. Moreover, we aimed to investigate the association of CD19 + CD25 + Bregs with serum IL-10, TGF-ß1, and IFN-γ in the same study groups. METHOD: Thirty-one healthy controls, ninety renal transplant recipients, and eighteen ESKD patients were enrolled. We evaluated the CD19 + CD25 + Bregs and Treg absolute counts. Next, we investigated CD19 + CD25 + Bregs as predictors of good graft function in multiple regression and ROC analyses. Finally, we evaluated the association between CD19 + CD25+ Bregs and serum IL-10, TGF-ß, and IFN-γ. RESULTS: ESKD patients and renal transplant recipients showed lower counts of CD19 + CD25+ Bregs compared to healthy controls (p < 0.001). Higher CD19 + CD25+ Breg counts were independently associated with a better GFR in renal transplant recipients (unstandardized B coefficient = 9, p = 0.02). In these patients, higher CD19 + CD25+ Bregs were independently associated with higher Treg counts (unstandardized B = 2.8, p = 0.004). In ROC analysis, cut-offs for CD19 + CD25 + Breg counts and serum TGF-ß1 of 0.12 cell/µl and 19,635.4 pg/ml, respectively, were shown to provide a good sensitivity and specificity in identifying GFR ≥ 30 ml/min (AUC = 0.67, sensitivity 77%, specificity 43%; AUC = 0.65, sensitivity 81%, specificity 50%, respectively). Finally, a significant positive association between CD19 + CD25+ Bregs and TGF-ß1 was shown in renal transplant recipients (r = 0.255, p = 0.015). CONCLUSIONS: Our findings indicate that higher counts of CD19 + CD25+ Bregs are independently associated with better renal function and higher absolute Treg counts in renal transplant recipients.

Possible Role of CD11a in Primary Immune Thrombocytopenia Patients on Immunosuppressive Therapy.

BACKGROUND AND OBJECTIVES: Immune thrombocytopenia (ITP) is one of the autoimmune diseases that presented by thrombocytopenia and increased risk of bleeding. Etiology of immune thrombocytopenia (ITP) is very complex. Lymphocyte function associated antigen-1 (LFA-1) plays important role in ITP. The aim of this study was evaluation of expression of CD11a on lymphocytes to explore its possible role in primary ITP patients also, regarding severity and response to immunosuppressive treatment. PATIENTS AND METHODS: This is a cross-sectional case-control study. Forty adult patients aged (18:58) years, 29 females and 11 males were enrolled as newly diagnosed primary ITP. Forty age and sex matched control subjects were randomly selected. The expression of CD11a on lymphocyte subpopulations (CD3+ T cells, CD3+CD4+ T cells and CD19+ B cells) was analyzed by flowcytometry at the start of the study and after 6 months of follow-up. RESULTS: The mean fluorescence intensity (MFI) of CD11a on CD3+ T and CD19+ B lymphocytes was significantly highly increased in ITP patients compared to healthy controls while MFI of CD11a on CD3+ CD4+Tclls was non-significant. MFI of CD11a on CD3+ and CD19+ B lymphocytes showed non-significant elevation with platelet count or bleeding score. MFI of CD11a on CD3+ showed significant highly increased level in refractory ITP compared with responder cases. CONCLUSION: CD11a had possible role in the pathogenesis of ITP. Immunosuppressive therapy in ITP did not affect the level of CD11a expression on T and B lymphocytes. Levels of CD11a do not reflect the severity of ITP neither platelet count nor bleeding score. Increased MFI of CD11a in CD3+T lymphocytes of ITP patients may cause resistance to immunosuppressive therapy.

Knowledge, perceptions and attitude of Egyptian physicians towards biobanking issues.

OBJECTIVES: Collection and storage of biospecimens and data for biobanking raise many ethical concerns. Stakeholders' opinions about these ethical issues are important since they can help in the development of ethical guidelines to govern biobanking activities. Physicians are among the important stakeholders since they contact potential participants and could be biobank users. The goal of this study is to evaluate the perceptions and attitude of Egyptian physicians towards ethical issues in biobanking. METHODS: A cross-sectional online survey was designed and distributed with the target group between November 2019 and January 2020. RESULTS: The questionnaire was completed by 223 physicians. While 65.5% reported hearing the term "Biobanking" before, 45.7% knew that there are biobanks in Egypt. Participants had a general positive attitude towards the value of biobanks in research. About 73% agreed that biobanks can share biospecimens with international research organizations, but only 42.6% supported collaboration with pharmaceutical companies, and 44% agreed to the use of user fees by biobanks. About 48% supported the use of broad consent in biobanks, and 73.1% believed that donors of biospecimens should be informed about results of research performed on their biospecimens. CONCLUSION: Although many Egyptian physicians heard about biobanking, they had limited knowledge about the existence of biobanks in Egypt. They had concerns about commercialization, use of broad consent and user fees. A knowledge gap exists among these stakeholders, which should be covered by different educational activities. Community discussions should start to reach consensus about the issues of commercialization and return of research results.

Revisiting the management of chronic ITP; a randomized controlled clinical trial.

The balance between therapy effectiveness and economic efficiency in chronic immune thrombocytopenia (ITP) becomes more confusing. This single-center open label randomized controlled trial evaluates the effectiveness and safety of hydroxychloroquine in chronic ITP patients against other affordable second-line treatments. It is registered under number (NCT03229746) at Clinical Trials.gov. 120 patients were recruited and randomly allocated to three arms of hydroxychloroquine, vincristine, and azathioprine equally. Platelet counts of more than 100 × 109/L were interpreted as complete response (CR), while response (R) was determined as platelet counts ranging from 30 × 109/L to less than 100 × 109/L with the doubling of the pretreatment platelet count. Overall response (OR) was defined to include both CR and R. Patients were monitored every 6 weeks for a total of 24 weeks. The population baseline characteristics regarding age, sex, duration of the disease, baseline platelets count, and presence of antinuclear antibodies ANA or antiplatelet antibodies were similar among tested groups. There was a significant difference in the overall response between hydroxychloroquine (80.6%) and azathioprine (55.9%) (p-value <0.05). This difference was not significant between hydroxychloroquine and vincristine group (63.2%) (p-value = 0.09). This study proves that hydroxychloroquine can contribute to the therapy of chronic ITP especially as an affordable and well-tolerated drug.

Altered Regulatory B Cell Subsets in Children with Type 1 Diabetes Mellitus.

B regulatory cells (Breg) refer to characteristic subsets of B cells that generally exert anti-inflammatory functions and maintain peripheral tolerance mainly through their ability to secrete interleukin-10 (IL10). Dysregulation in the function of Breg cells was reported in several autoimmune diseases. However, the relation between Breg and children with type 1 diabetes (T1D) is poorly understood. Thus, this study is aimed at determining whether Breg cells play a role in T1D in children or not, so we hypothesized that an altered phenotype of B cell subsets is associated with T1D in children. Children with T1D (n = 29) and control children with normal blood glucose levels (n = 14) were recruited. The percentages of different circulating IL10-producing Breg subsets, including B10, immature transitional, and plasmablasts were determined using flow cytometry analysis. Furthermore, the association between different IL10-producing B cells and patient parameters was investigated. The percentage of circulating IL10+CD24hiCD27+ (B10) and IL10+CD24hiCD38hi (immature transitional) subsets of Breg cells was significantly lower in T1D patients than in healthy controls. Moreover, these cells were also negatively correlated with fasting blood glucose and HbA1c levels. Breg cells did not correlate with autoantibody levels in the serum. These findings suggest that certain Breg subsets are numerically deficient in children with T1D. This alteration in frequency is associated with deficient islet function and glycemia. These findings suggest that Breg cells may be involved in the loss of auto-tolerance and consequent destruction of pancreatic cells and could, therefore, be a potential target for immunotherapy.

Synthesis of a novel series of (Z)-3,5-disubstituted thiazolidine-2,4-diones as promising anti-breast cancer agents.

A novel series of (Z)-3,5-disubstituted thiazolidine-2,4-diones 4-16 has been designed and synthesized. Preliminary screening of these compounds for their anti-breast cancer activity revealed that compounds 5, 7, and 9 possess the highest anti-cancer activities. The anti-tumor effects of compounds 5, 7, and 9 were evaluated against human breast cancer cell lines (MCF-7 and MDA-MB-231) and human breast cancer cells. They were also evaluated against normal non-cancerous breast cells, isolated from the same patients, to conclude about their use in a potential targeted therapy. Using MTT uptake method, these three compounds 5, 7, and 9 blunt the proliferation of these cancer cells in a dose-dependent manner with an IC50 of 1.27, 1.50 and 1.31 µM respectively. Interestingly, using flow cytometry analysis these three compounds significantly mediated apoptosis of human breast cancer cells without affecting the survival of normal non-cancerous breast cells that were isolated from the same patients. Mechanistically, these compounds blunt the proliferation of MCF-7 breast cancer cells by robustly decreasing the phosphorylation of AKT, mTOR and the expression of VEGF and HIF-1α. Most importantly, compounds 5, 7, and 9 without affecting the phosphorylation and expression of these crucial cellular factors in normal non-cancerous breast cells that were isolated from the same patients. Additionally, using Western blot analysis the three compounds significantly (P < 0.05) decreased the expression of the anti-apoptotic Bcl-2 members (Bcl-2, Bcl-XL and Mcl-1) and increased the expression of the pro-apoptotic Bcl-2 members (Bak, Bax and Bim) in MCF-7, MDA-MB-231 and human breast cancer cells making these breast cancer cells susceptible for apoptosis induction. Taken together, these data provide great evidences for the inhibitory activity of these compounds against breast cancer cells without affecting the normal breast cells.

Hepatitis C Virus Affects Tuberculosis-Specific T Cells in HIV-Negative Patients.

The occurrence of tuberculosis (TB) and hepatitis C virus (HCV) infections in the same patient presents a unique clinical challenge. The impact of HCV infection on the immune response to TB remains poorly investigated in TB+/HCV+ patients. This study was conducted to evaluate the impact of HCV on the T-cell-mediated immune response to TB in coinfected patients. Sixty-four patients with active TB infections were screened for coinfection with HCV. The expression of immune activation markers IFN-γ, CD38, and HLA-DR on TB-specific CD4+ T cells was evaluated by flow cytometry in TB-monoinfected patients, TB/HCV-coinfected patients, and healthy controls. IL-2, IL-4, IFN-γ, TNF-α, and IL-10 levels were measured using ELISA. The end-of-treatment response to anti-TB therapy was recorded for both patient groups. Significantly lower levels of CD4+IFN-γ+CD38+ and CD4+IFN-γ+HLA-DR+ T cells were detected in TB/HCV-coinfected patients compared to TB monoinfected patients and controls. TB+/HCV+-coinfected patients showed higher serum levels of IL-10. The baseline frequencies of TB-specific activated T-cell subsets did not predict the response to antituberculous therapy in TB+/HCV+ patients. We concluded that different subsets of TB-specific CD4+ T cells in TB/HCV-infected individuals are partially impaired in early-stage HCV infection. This was combined with increased serum IL-10 level. Such immune modulations may represent a powerful risk factor for disease progression in patients with HCV/TB coinfection.

Periostin expression and characters of human adipose tissue-derived mesenchymal stromal cells were aberrantly affected by in vitro cultivation.

BACKGROUND: Human adipose tissue-derived mesenchymal stromal cells (AD-MSCs) have been under focus in regenerative medicine since their discovery as a suitable source of MSCs. AD-MSCs are heterogeneous cells and exhibit variations in population doubling time, morphology and proliferative capacity. This study investigated if human AD-MSCs are developing, during in vitro long-term cultivation, in an unwanted or aberrant way. METHODS: This study monitored AD-MSCs during their in vitro culture till the tenth passage investigating proliferation kinetics, DNA index and surface markers expression. Also, periostin gene expression was examined. RESULTS: The proliferation capacity and colony forming unit were decreased after passage 6 and the population doubling time was increased. Flow cytometric analysis revealed that newly cultivated population strongly expressed MSCs markers, furthermore, reduction of CD105 expression appeared in passage 5 onwards, the later was associated with significant increase in expression of CD34 (a hematopoietic cell marker). Also, reduction of CD73 and CD90 expression was observed from passage 8. Furthermore, during the first six passages, periostin expression was significantly unchanged, with significant upregulation in late passages. CONCLUSIONS: Long-term cultivation of human AD-MSCs changed their characters in an aberrant way and the first four passages might be the most appropriate passages for therapy. More investigation and understanding of these variations are needed to help in standardizing the expansion of MSCs-based therapies.

What Egyptians think. Knowledge, attitude, and opinions of Egyptian patients towards biobanking issues.

BACKGROUND: Biobanking is a relatively new concept in Egypt. Building a good relationship with different stakeholders is essential for the social sustainability of biobanks. To establish this relationship, it is necessary to assess the attitude of different groups towards this concept. The objective of this work is to assess the knowledge, attitude, and opinions of Egyptian patients towards biobanking issues. METHODS: We designed a structured survey to be administered to patients coming to the outpatient clinics in 3 university hospitals in Egypt. The survey included questions estimating the level of knowledge about the term "Biobank", together with questions about the attitudes and opinions about related issues. RESULTS: Two hundred and fifty-nine patients participated in the survey. Eighty-one percent of participants reported that they never heard about the term before. About 85% expressed that they would be willing to donate their samples for research and about 87% thought that sample donation did not contradict their religious beliefs. Fifty eight percent were willing to participate in a genetic research project, 27.8% supported sharing their sample with pharmaceutical companies, and 32.4% agreed to share their samples with institutions abroad. CONCLUSION: Although there is limited knowledge about biobanking among Egyptian patients, many had a positive attitude towards sample donation and didn't show religious concerns against it. However, they showed concerns regarding participation in genetic research and with sharing their samples across borders or with pharmaceutical companies. Public education about biobanking is possible, taking into consideration the specific cultural and legal framework in Egypt.

Enhanced susceptibility to apoptosis and growth arrest of human breast carcinoma cells treated with silica nanoparticles loaded with monohydroxy flavone compounds.

The treatment of drug-resistant cancer is a clinical challenge, hence screening for novel anticancer drugs is critically important. In this study, we investigated the anti-tumor potential of three plant-derived flavone compounds: 3-hydroxy flavone (3-HF), 6-hydroxy flavone (6-HF), and 7-hydroxy flavone (7-HF), either alone or combined with silica nanoparticles (3-HF + NP, 6-HF + NP, and 7-HF + NP), on the human breast carcinoma cell lines MDA-MB-231 and MCF-7, as well as on non-tumorigenic normal breast epithelial cells (MCF-10). The IC50 values of these flavone compounds loaded with NP (flavones + NP) in these cell lines were determined to be 1.5 µg/mL without affecting the viability of normal MCF-10 cells. Additionally, using annexin V - propidium iodide double-staining followed by flow cytometry analysis, we found that the combination of flavones with NP significantly induced apoptosis in MCF-7 and MDA-MB-231 cancer cells. Furthermore, flavones + NP increased the expression of cytochrome c and caspase-9, mediating the growth arrest of these cancer cells. Most importantly, the combination of flavones with NP significantly abolished the expression of ATF-3, which is responsible for the proliferation and invasion of bone-metastatic breast cancer cells. Our data revealed the potential therapeutic effects of these flavones in fighting breast cancer cells, and provide the first insights concerning the underlying molecular mechanisms.

Relation of Regulatory Foxp3+ T Cells with Helicobacter pylori and Its Virulence Genes.

The study aimed to assess the tangled relation between various CD25 subsets (positive, negative and high) of CD4+ FoxP3+ T cells and H. pylori including its virulence genes (CagA and VacA). Diagnosis of H. pylori and its virulence genes was based on a positive culture, histopathology and/or CLO-test and PCR. Flow cytometry was used toquantifyTregs.CD4+CD25high Foxp3+ T cells were higher in patients than controls and somewhat more in H. pylori positive than negative patients. CD4+CD25high Foxp3+ T cells secreting IL10 were lower in H. pylori positive patients.CD4+CD25-Fox3+T cells were also higher in patients than controls and more in those negative for H. pylori. Moderate negative correlation was found between the presence of CagA or VacA sm genotypes and Tregs secreting IL10. CD4+CD25- Foxp3+ T cells, especially those secreting IL10, tend to be higher in patients carrying VacA m1 allele than m2 allele. In conclusion, H. pylori stimulate a regulatory T cell response, probably contributing to gastric diseases. CD25 negative subset of Fox3+CD4+T cells needs further studying to declare its potential role in immunopathogenesis of gastric diseases. Tregs are positively associated with vacA alleles.

Author Correction: Strong associations between chromosomal aberrations in blood lymphocytes and the risk of urothelial and squamous cell carcinoma of the bladder.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Fluorouracil-Loaded Gold Nanoparticles for the Treatment of Skin Cancer: Development, in Vitro Characterization, and in Vivo Evaluation in a Mouse Skin Cancer Xenograft Model.

Fluorouracil (5-FU) is an antimetabolite drug used in the treatment of various malignancies, such as colon and skin cancers. However, its systemic administration results in severe side effects. Topical 5-FU delivery for the treatment of skin cancer could circumvent these shortcomings, but it is limited by the drug poor permeability through the skin. To enhance 5-FU efficacy against skin cancer and reduce its systemic side effects, it was loaded into a gold nanoparticle (GNP)-based topical delivery system. 5-FU was loaded onto GNPs capped with CTAB through ionic interactions between 5-FU and CTAB. GNPs were prepared at different 5-FU/CTAB molar ratios and evaluated using different techniques. GNP stability and drug release were studied as a function of salt concentration and solution pH. Optimum 5-FU/CTAB-GNPs were incorporated into gel and cream bases, and their ex vivo permeability was evaluated in mice dorsal skin. The in vivo anticancer efficacy of the same preparations was evaluated in A431 tumor-bearing mice. The GNPs had spherical shape and a size of ∼16-150 nm. Maximum 5-FU entrapment was achieved at 5-FU/CTAB molar ratio of 1:1 and pH 11.5. Drug release from GNPs was sustained and pH-dependent. 5-FU GNP gel and cream had around 2-fold higher permeability through mice skin compared with free 5-FU gel and cream formulations. Further, in vivo studies in a mouse model having A431 skin cancer cells implanted in the subcutaneous space showed that the GNP gel and cream achieved 6.8- and 18.4-fold lower tumor volume compared with the untreated control, respectively. These results confirm the potential of topical 5-FU/CTAB-GNPs to enhance drug efficacy against skin cancer.

Strong associations between chromosomal aberrations in blood lymphocytes and the risk of urothelial and squamous cell carcinoma of the bladder.

Chromosomal aberrations (CAs) in blood lymphocytes have been shown to be associated with overall cancer risk and aging. However, their relationship to bladder cancer risk remains to be elucidated. In a case-control study of bladder cancer in Egypt, we examined the relationship between the increased frequency of CAs in blood lymphocytes and bladder cancer risk. High frequency of CAs was significantly associated with an increased risk of bladder cancer [adjusted odds ratios (OR) = 3.90, 95% confidence interval (CI) = 2.65-5.73]. The associations were somewhat stronger in squamous cell carcinomas (SCC, OR = 4.90) than in urothelial carcinomas (UC, OR = 3.62). We also identified chromosome specific CAs for chromosomes 3, 4, 5, 8, 9, 10, 11, 12, 17, 19 that were significantly associated with an increased risk of bladder cancer. We observed particularly strong associations between aberrations of chromosomes 12, 13, 17 and risk of SCC (OR = 7.06, 6.91 and 6.23, respectively). CONCLUSION: increased frequency of chromosomal aberrations in blood lymphocytes was significantly associated with bladder cancer risk. Overall and chromosome specific aberrations in blood lymphocytes may be a unique set of biomarkers for risk assessments of SCC and UC.

Non-neoplastic Portal Vein Thrombosis in HCV Cirrhosis Patients: Is it an Immuno-Inflammatory Disorder?

BACKGROUND AND AIMS: Portal vein thrombosis (PVT) is a critical complication in cirrhotic patients. We explored the role of the activated factor VII-antithrombin (FVIIa-AT) complex and enhanced monocytic tissue factor (TF) expression in the development and prediction of non-neoplastic PVT in cirrhotic patients. MATERIAL AND METHODS: A total of 30 HCV-cirrhosis patients were included in our study. They were compared to 35 cirrhotic patients without PVT, 15 non-cirrhotic patients with PVT, and 15 healthy controls. The plasma level of the FVIIa-AT complexes was analyzed by ELISA. MIF CD142, CD86, and HLA-DR on monocytes (CD14) were determined by flow cytometry. RESULTS: Compared with cirrhotic patients without PVT, cirrhotic patients with PVT had comparable plasma values of FVIIa, AT, and the FVIIa-AT complex. However, they had significantly lower values compared to non-cirrhotic patients with PVT and healthy controls. Cirrhotic patients with PVT had increased monocytic TF expression (MIF CD142) compared to non-PVT cirrhotic patients and healthy controls [86.5 (93.5) vs. 18 (32.0) and 11.0 (6.0), respectively; p < 0.001 for each]. However, cirrhosis PVT could not be distinguished from non-cirrhosis PVT. The area under the ROC curve of MIF CD142 was 0.759 (0.641- 0.876; p = 0.000) at an optimal cut-off value of 45, which yielded a sensitivity of 60% and a specificity of 77.1%, as well as a PPV and NPV of 69.2% for each. CONCLUSION: Enhanced expression of monocytic TF may have a role in the development and prediction of non-neoplastic PVT in HCV-cirrhosis patients. Large multicenter studies are necessary to validate our results.