Motawa E. El-Houseini

Enhanced detection of hepatocellular carcinoma.

BACKGROUND Tumor markers in the early detection of tumors are promising tools that could improve the control and treatment of tumors. While alpha-fetoprotein (AFP) is a commonly used tumor marker in the detection of hepatocellular carcinoma (HCC), its sensitivity and specificity are insufficient to detect HCC in all patient samples. METHODS We compared AFP with serum levels of vascular endothelial growth factors (VEGF and VEGF-A), insulin-like growth factor-2 (IGF-II), and the activity of the lysosomal enzyme alpha-L-fucosidase (AFU) in the sensitivity of detection of HCC and cirrhosis in Egyptian patients. RESULTS The sensitivity of tumor detection using AFP was 68.2%. This level of detection was increased to 88.6% when AFP was evaluated in conjunction with AFU. The combined use of AFP and VEGF increased the sensitivity of detection to 95.5% in patients with HCC. The combination of the three markers yielded 100% detection sensitivity. VEGF-A showed a low specificity (20%), and IGF-II showed extremely low sensitivity (4.5%). CONCLUSIONS We suggest that AFU or VEGF or both be measured with AFP to improve the detection sensitivity of HCC.

Serological biomarkers of hepatocellular carcinoma in Egyptian patients

Hepatocellular carcinoma (HCC) is one of the most aggressive cancers worldwide. In Egypt, the disease is usually detected in an advanced stage at which no treatment may be effective including surgery. Early detection of the disease is thus an important goal allowing the patient to be treated before the enlargement of the tumor or its metastasis to distant organs. Tumor markers are serological agents which serum level may be useful in predicting the presence of the tumor at early stages. Alpha fetoprotein (AFP) which is the golden marker for HCC is of low sensitivity, therefore, additional markers such as alpha-L-fucosidase (AFU), transforming growth factors alpha and beta (TGF-α and TGF-β) and interleukin-8 (IL-8) are suggested to be simultaneously evaluated in order to enhance the detection of HCC. A total of 96 patients with different liver diseases such as HCC, hepatitis C virus (HCV), hepatitis B virus (HBV) and cirrhotic patients are included in this study. Sixteen healthy volunteers are used as a control group. In patients with HCC each of AFP, AFU, TGF-α and TGF-β recorded significantly higher levels than the other patient groups and controls. HCC patients recorded significantly lower level of IL-8 compared to the other patient groups but significantly higher than the control. For AFP, AFU, TGF-α, TGF-β and IL-8, at the optimal cut-off values (obtained from the receiver operating characteristic (ROC) curves), the calculated sensitivities are 46%, 72.97%, 67.56%, 54.05% and 83.8%, respectively. The simultaneous evaluation using all of the suggested markers resulted in increasing the sensitivity up to 100%. It thus recommended that, if patients with cirrhosis, as high risk patients, are subjected to regular examination using these markers in addition to AFP, HCC may be detected by 100% sensitivity in an early stage and as a consequence an effective treatment can be achieved.

Characterization of cirrhosis and hepatocellular carcinoma using low-angle x-ray scattering signatures of serum

The diagnosis of hepatocellular carcinoma (HCC) usually occurs at late stages in the disease when there are few effective treatment options. The measurement of the concentration of tumour markers in the serum of patients is a complementary tool frequently used for the interpretation of diagnostic imaging results. It is also used as a prognostic tool for the detection of cancer. Unfortunately, the sensitivity of tumour markers is still low and many times it yields normal results for cirrhotic and HCC patients. In the current work, the detection possibility of the structural changes in serum proteins accompanying cirrhosis and HCC is investigated using a low-angle x-ray scattering (LAXS) technique. The results show that there are significant differences in the LAXS profiles of cirrhosis and HCC lyophilized serum samples compared to normal. The changes in shape, total counts and position of the first scattering peak at 4.8 degrees, which was previously reported to be sensitive to the structural changes in protein, showed the most characteristic deviations from normal serum. The present results are promising and would offer a potentially helpful complementary tool for monitoring cirrhosis and HCC.

Potential role of curcumin and taurine combination therapy on human myeloid leukemic cells propagated in vitro.

Abstract Curcumin and taurine are natural products that have been used in this study evaluating their therapeutic effect on myeloid leukemic cells propagated in vitro. Sixty patients with myeloid leukemia and 30 healthy volunteers were enrolled in the study. All patient groups were admitted to the Medical Oncology Department of the National Cancer Institute, Cairo University. There were statistically significant differences between treated leukemic cells compared to normal mononuclear leukocytes in cell density, interferon-γ and immunophenotypic profile, mainly CD4+, CD8 + and CD25+. This work highlights the possibility of using curcumin and taurine as a potential useful therapy in the management of patients suffering from chronic and acute myeloid leukemias.

Potential immunotherapeutic role of interleukin-2 and interleukin-12 combination in patients with hepatocellular carcinoma

Background Many recent therapeutic interventions are necessary to improve the treatment of hepatocellular carcinoma (HCC), including immunotherapy, which seems to offer one of the new realistic therapeutic modalities. This study aims to investigate the optimization of immunotherapy for HCC patients by appraisal of both interferon (IFN)-γ levels and phenotyping of lymphocytes obtained from peripheral blood and fine-needle aspirates. Methods The isolated lymphocytes were cultured in the presence of interleukins (IL)-2, IL-4, and IL-12. Enzyme-linked immunosorbent assay and flow cytometric techniques were used for the assessment of human IFN-γ production and the studied T-cell subpopulations, respectively. Results Mixed cell populations of peripheral blood lymphocytes and tumor infiltrating lymphocytes treated with IL-2 plus IL-12 showed a marked and significant elevation in IFN-γ levels in their culture media, a significant decrease in the percentage of cluster of differentiation (CD)4+CD25+ regulatory T-cells, and a nonsignificant increase in the percentage of CD8+ cytotoxic T-cells. Meanwhile, IL-2 plus IL-4 treatment demonstrated nonsignificant effects. Conclusion Our data suggested that IL-12 together with IL-2 caused a suppression of CD4+CD25+ regulatory T-cells and an elevation of IFN-γ levels, which play a crucial immunotherapeutic role in the management of HCC patients.

HepG2 Attenuation Induced by RNase A Modulates Gene Profiling and Immunophenotypic Characterization of Some Immune Cells Operating in Cancer Vaccine

Hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer death. Attempts to induce an effective immune response against cancer by immunotherapeutic intervention, including activation of dendritic cells (DCs), were established. The present study was undertaken to investigate the attenuation of HepG2 cells using ribonuclease enzyme A (RNase A) as a possible biological factor to sensitize allogenic DCs and lymphocytes isolated from Egyptian HCC patients. Attenuation of HepG2 cells resulted in a significant increase in activated DC and T-lymphocyte markers, upregulation of CD44 gene expression and increased lactate dehydrogenase as well as interleukin-12 levels. In contrast, a significant decrease in matureDCs, B-cells, T-helper, cytotoxic T-cells, and NK-cells, as well as LMP-2 gene expression was recorded. In conclusion, the attenuation of HepG2 cells with RNase A and subsequent pulsation to allogenic DCs and lymphocytes caused a differential immune response. Further studies are recommended to explain the role of RNase A in modulating antigen expression on the tumor cell surface.

Cancer cell death induced by nanomagnetolectin

Magnetic nanoparticles represent a new paradigm for molecular targeting therapy in cancer. However, the transformative targeting potential of magnetic nanoparticles has been stymied by a key obstacle-safe delivery to specified target cells in vivo. As cancer cells grow under nutrient deprivation and hypoxic conditions and decorate cell surface with excessive sialoglycans, sialic acid binding lectins might be suitable for targeting cancer cells in vivo. Here we explore the potential of magnetic nanoparticles functionalized with wheat germ lectin (WGA) conjugate, so-called nanomagnetolectin, as apoptotic targetable agents for prostate cancer. In the presence of magnetic field (magnetofection) for 15min, 2.46nM nanomagnetolectin significantly promoted apoptosis (∼12-fold, p value <0.01) of prostate cancer cells (LNCaP, PC-3, DU-145) compared to normal prostate epithelial cells (PrEC, PNT2, PZ-HPV-7), when supplemented with 10mM sialic acid under nutrient deprived condition. Nanomagnetolectin targets cell-surface glycosylation, particularly sialic acid as nanomagnetolectin induced apoptosis of cancer cells largely diminished (only 2 to 2.5-fold) compared to normal cells. The efficacy of magnetofected nanomagnetolectin was demonstrated in orthotopically xenografted (DU-145) mice, where tumor was not only completely arrested, but also reduced significantly (p value <0.001). This was further corroborated in subcutaneous xenograft model, where nanomagnetolectin in the presence of magnetic field and photothermal heating at ∼42°C induced apoptosis of tumor by ∼4-fold compared to tumor section heated at ∼42°C, but without magnetic field. Taken all together, the study demonstrates, for the first time, the utility of nanomagnetolectin as a potential cancer therapeutic.

Protective Role of Magic Fruit and Honey Bee against Human Hepatocarcinogenesis

Background: Hepatitis C is an infectious disease that affects the liver. Its complication is a major high-risk group that may be lead to hepatocellular carcinoma HCC, so natural prevention is required. The combination of magic fruit and honey bee was used in the treatment of HCV patients were treated with 4 g from Magic fruit and 1 g from Honey bee 3 times daily for three months. Methods and findings: Our group study was conducted on 50 patients with chronic hepatitis C (the male number was 35 while the female was 15; the median age was 45 years) was taken from the outpatient clinics of NCI, Egypt. Results: The mean values of virus C level, which was determined by real time PCR and FoxP3 protein which was measured by ELISA in sera of patients with chronic hepatitis infection (CHI), showed highly significant decrease after treatment. Hence the results have shown improvements in liver function, kidney function, and CBC tests for the HCV patients post-treatment. Moreover, the results revealed also that, highly significant decreased of CD4 + CD25 expression by flow cytometric analysis was observed in the mononuclear leukocytes isolated from the patients after treatment. Conclusion: A combination of magic fruit and honey bee could be useful protective natural agents against human hepatocarcinogenesis induced by HCV infection. Further study is strongly recommended for large populations and prolonged treatment for 9-12 months.