Clinical assessment of TGFB1 and HP Relative Gene Expression in the Peripheral Blood of Prostate Cancer Patients.

OBJECTIVE: This study aimed to assess the relative gene expression level of transforming growth factor-ß1 (TGFB1) and haptoglobin (HP) in the peripheral blood of prostate cancer (PCa) patients and evaluate their diagnostic ability. METHODS: A total of 125 participants were enrolled in the present study. Among them, 75 PCa patients, 25 benign prostatic hyperplasia (BPH) patients, and 25 healthy volunteers served as the control group. The relative TGFB1 and HP gene expression level was quantified using real-time polymerase chain reaction. Further, free and total PSA levels were determined using electrochemiluminescence assays. RESULTS: TGFB1 was significantly over-expressed, whereas HP was significantly downregulated in the peripheral blood of PCa patients compared to BPH and control groups (p-value ranges from 0.034 to <0.001). Moreover, the high expression level of TGFB1 was associated with an increased risk of PCa development with OR=1.412 (95%CI: 1.081-1.869, p= 0.012). TGFB1 and HP relative expression levels had lower diagnostic performance to differentiate PCa from normal and BPH individuals compared to PSA, however, the combination of the tested parameters improved the diagnostic efficacy. CONCLUSIONS: TGFB1 and HP relative expression have moderate diagnostic efficacy in discriminating patients with PCa from BPH and healthy subjects. Furthermore, over-expression of TGFB1 may contribute to the pathogenesis of PCa.

Moxifloxacin-loaded in situ synthesized Bioceramic/Poly(L-lactide-co-ε-caprolactone) composite scaffolds for treatment of osteomyelitis and orthopedic regeneration.

High local intraosseous levels of antimicrobial agents are required for adequate long-term treatment of chronic osteomyelitis (OM). In this study, biodegradable composite scaffolds of poly-lactide-co-ε-caprolactone/calcium phosphate (CaP) were in-situ synthesized using two different polymer grades and synthesis pathways and compared to composites prepared by pre-formed (commercially available) CaP for delivery of the antibiotic moxifloxacin hydrochloride (MOX). Phase identification and characterization by Fourier transform infra-red (FTIR) spectroscopy, X-ray powder diffraction (XRPD) and scanning electron microscope (SEM) confirmed the successful formation of different CaP phases within the biodegradable polymer matrix. The selected in-situ formed CaP scaffold showed a sustained release for MOX for six weeks and adequate porosity. Cell viability study on MG-63 osteoblast-like cells revealed that the selected composite scaffold maintained the cellular proliferation and differentiation. Moreover, it was able to diminish the bacterial load, inflammation and sequestrum formation in the bones of OM-induced animals. The results of the present work deduce that the selected in-situ formed CaP composite scaffold is a propitious candidate for OM treatment, and further clinical experiments are recommended.

Chitosan-calcium phosphate composite scaffolds for control of post-operative osteomyelitis: Fabrication, characterization, and in vitro-in vivo evaluation.

Osteomyelitis is a progressive inflammatory disease requiring prolonged systemic treatment with high antibiotic doses, and is very challenging to be treated. The use of locally applied antibiotics loaded on a biodegradable carrier at surgery sites is hypothesized to prevent post-operative osteomyelitis, while providing site-specific drug release. In this work, chitosan-based calcium phosphate composites were prepared and loaded with moxifloxacin hydrochloride. The in-situ formation of calcium phosphates within the composite was experimentally confirmed by Fourier transform infra-red spectroscopy, X-ray powder diffraction, and scanning electron microscopy. Results showed that the composites provided complete drug release over three days, and the selected composite formulation induced differentiation and proliferation of osteoblasts, while reducing bacterial count, inflammation and intra-medullary fibrosis in bone tissue specimens of osteomyelitis-induced animal model. Hence, we can conclude that the in situ prepared antibiotic-loaded calcium phosphate chitosan composite is promising in preventing post-operative osteomyelitis, and is worthy of clinical experimentation.

Significance of Some Proliferation Markers and Some Prognostic Factors in Patients with Multiple Myeloma and their Impact on the Patients' Survival.

BACKGROUND: Multiple myeloma (MM) is influenced by genetic and micro-environmental changes. Malignant plasma cells produce an abnormal monoclonal immunoglobulin, as well as cytokines, such as IL-10 and IL-6 which stimulate cells of the bone marrow microenvironment (BMM) and cause dysfunction and failure of many organs. B cell activating factor (BAFF), IL6, IL10 are known to influence the growth and survival of the malignant clone. AIM: The objectives of the present study were to investigate the circulating levels of BAFF , IL-10 and IL-6 , correlate them with well-known parameters of disease activity in patients with MM, and to detect their impact on the patients' survival. MATERIALS AND METHODS: This study was conducted on 89 newly diagnosed MM patients and seventy apparently healthy volunteers as a normal control group. BAFF, IL6, IL10 were measured by ELISA for both groups. Survival analysis was performed for all patients. RESULTS: Studied markers were higher in the MM patients compared to the normal control subjects. Patients' survival was improved by high serum BAFF levels. CONCLUSIONS: High levels of BAFF were found to improve patients' survival. BAFF and IL-6 can be considered probable diagnostic markers for MM.

Significance of Proliferation Markers and Prognostic Factors in Egyptian Patients with Multiple Myeloma.

BACKGROUND: Multiple myeloma (MM) is influenced by genetic and micro-environmental changes. Malignant plasma cells produce an abnormal monoclonal immunoglobulin, as well as cytokines, such as IL-10 and IL-6 which stimulate cells of the bone marrow microenvironment (BMM) and cause dysfunction and failure of many organs. B cell activating factor (BAFF), IL6 and IL10 are known to influence the growth and survival of malignant clones. AIM: The objectives of the present study were to investigate the circulating levels of BAFF , IL-10 and IL-6, correlate them with well-known parameters of disease activity in patients with MM, and to detect their impact on patients' survival. MATERIALS AND METHODS: This study was conducted on 89 newly diagnosed MM patients and seventy apparently healthy volunteers as a normal control group. BAFF, IL6, IL10 were measured by ELISA for both groups and survival analysis was performed for all patients. RESULTS: Studied markers were higher in the MM patients compared to the normal control subjects. Patients survival was improved by high serum BAFF levels. CONCLUSIONS: High levels of BAFF were found to improve patients' survival. BAFF and IL-6 can be considered probable diagnostic markers for MM.

KIAA0101 mRNA expression in the peripheral blood of hepatocellular carcinoma patients: Association with some clinicopathological features.

OBJECTIVES: The development of hepatocellular carcinoma (HCC) is multi-factorial, multi-step and involving many genes. Recent studies have revealed the involvement of KIAA0101 in HCC development and progression. KIAA0101 is involved in the regulation of DNA repair, cell cycle progression, and cell proliferation. This study aims to elucidate the clinicopathological significance of KIAA0101 mRNA expression in the whole blood of HCC patients. DESIGN AND METHODS: This study was conducted on 77 patients with proven HCC who presented to the outpatient clinic at the National Cancer Institute - Cairo University over a period of 8 consecutive months. Thirty patients with cirrhosis and forty apparently healthy volunteers were included as control groups. Detection of KIAA0101 mRNA was done on whole blood collected on EDTA for all patients and control subjects using real-time PCR. RESULTS: KIAA0101 mRNA was over-expressed in the HCC group compared to the control groups. Overexpression of KIAA0101 mRNA was significantly associated with distant metastasis, advanced stage, high serum alkaline phosphatase and low serum albumin levels. Both sensitivity and specificity of KIAA0101 mRNA were higher than those of AFP and CEA. CONCLUSION: Being associated with some of the prognostic factors of HCC which reflect tumor progression; as advanced stage, distant metastasis, hypoalbuminemia and elevated serum alkaline phosphatase, together with its relatively high diagnostic performance; KIAA0101 mRNA might be nominated to play a probable role in the diagnosis and prognosis prediction of HCC. Further studies on a wider scale are recommended to confirm these results.

Comparing prothrombin induced by vitamin K absence-II (PIVKA-II) with the oncofetal proteins glypican-3, Alpha feto protein and carcinoembryonic antigen in diagnosing hepatocellular carcinoma among Egyptian patients.

BACKGROUND: Hepatocellular carcinoma (HCC) is usually asymptomatic in the early stage and does not show elevated alpha-feto protein (AFP). AFP shows 60-80% sensitivity in diagnosing HCC. Glypican3 (GPC-3) is an oncofetal protein that is only detected in HCC cells but not in benign liver tissues, while Carcinoembryonic antigen (CEA) is expressed in various neoplasms including HCC. Although, it is not specific for HCC. Prothrombin induced by vitamin K absence-II (PIVKA-II) is an abnormal prothrombin protein that is increased in the serum of HCC patients. It has higher sensitivity and specificity compared to AFP. The aim of this study is to compare the clinical utility of PIVKA-II with GPC-3, AFP and CEA in diagnosing HCC. PATIENTS AND METHODS: This study included 40 patients with HCC, 10 patients with cirrhosis as a benign control group, and 10 apparently healthy volunteers as normal controls. Serum samples were subjected to routine laboratory investigations, measurement of CEA, AFP using MEIA technique (Axsym), glypican3, and PIVKA-II using ELISA technique in the sera of all patients and controls. RESULTS: All markers showed the highest results in the HCC group. Higher concentrations of PIVKA-II were detected in patients with splenomegaly, and in tumors with size (>3cm). Combination of Glypican-3 and PIVKA-II showed the highest sensitivity, while GPC-3 alone and combination of GPC-3 and AFP showed the highest specificity to differentiate HCC from liver cirrhosis and normal controls. GPC-3, PIVKAII, and combination of both showed the highest sensitivity, while GPC-3 alone showed the highest specificity to differentiate HCC from liver cirrhosis. CONCLUSION: Glypican-3 is the only oncofetal antigen that showed comparable high diagnostic accuracy as PIVKA-II in diagnosing HCC among Egyptian patients.