Wael M. Elshemey

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.

Structural and electronic properties of new fullerene derivatives and their possible application as HIV-1 protease inhibitors.

Density functional theory (DFT) calculations have been carried out at the hybrid Becke 3-Lee-Yang-Parr; B3LYP/3-21G** level of theory to study two series of hydroxy-chalca-acetic acid-(4-pyrrolidin-1-yl-phenyl) ester [C(60)-C(2)H(4)N-(4-XCOCH(2)OH)C(6)H(4)] and hydroxy-chalcoacetic acid-[2-(2-hydroxy-acetylchalcanyl)-4-pyrrolidin-1-yl-phenyl] ester[C(60)-C(2)H(4)N-(3,4-XCOCH(2)OH)C(6)H(4)]. The X atom is O, S or Se for the two series. The vibrational spectra, physical, chemical, thermodynamics and Quantitative Structure Activity Relationship (QSAR) properties of the studied molecules are calculated and discussed. We have evaluated these molecules as HIV-1 protease inhibitors based on the hydrogenation interaction between the hydroxymethylcarbonyl (HMC) groups and the two aspartic acid of the HIV-1 protease active site. Results show that some of the investigated fullerene-based derivatives can be considered promising as HIV-1 protease inhibitors.

Correlation to Protein Conformation of Wide-Angle X-ray Scatter Parameters

In the last decade, several studies have reported that Wide-Angle X-ray Scattering (WAXS) from protein in solution contains valuable information about protein secondary and tertiary structures. Nevertheless, the use of such information will remain limited until a clear understanding of the correlation between protein structural elements and WAXS profile regions is established. In this work, large number of possible protein conformations is generated using comparative modeling (LOOPP & PHYRE servers) of nine different proteins representing six main protein classes (SCOP database). After model validation (SAVES server), protein structural elements of the selected models are retrieved (Swiss PDB Viewer & VORONOIA) and their corresponding WAXS profiles are generated (CRYSOL). The correlations between seven elements of protein structure (alpha helix, beta sheet and random coil content, alpha to beta ratio, alpha to random coil ratio, average packing density and number of residues) and seven WAXS profile parameters (Full Width at Half Maximum of two main scattering peaks of interest, their areas, positions and ratio of intensities) are investigated. Results revealed high (up to 0.75) and moderate (0.30–0.50) correlations between some of the suggested profile parameters and investigated protein structural elements indicating that these parameters represent a useful probe of protein conformation. Moreover, a high observed correlation between the degree of fitting of model to reference structures and the degree of fitting of their corresponding WAXS profiles suggests that the latter can be used in experimental model validation.

The diagnostic capability of x-ray scattering parameters for the characterization of breast cancer.

PURPOSE The evaluation of the diagnostic capability of easy to measure x-ray scattering profile characterization parameters for the detection of breast cancer in excised samples. The selected parameters are the full width at half maximum (FWHM) and area under the x-ray scattering profile of breast tissue in addition to the ratio of scattering intensities (I2/I1%) at 1.6 nm(-1) to that at 1.1 nm(-1) (corresponding to scattering from soft and adipose tissues, respectively). METHODS A histopathologist is asked to classify 36 excised breast tissue samples into healthy or malignant. A conventional x-ray diffractometer is used to acquire the scattering profiles of the investigated samples. The values of three profile characterization parameters are calculated and the diagnostic capability of each is evaluated by determining the optimal cutoffs of scatter diagrams, calculating the diagnostic indices, and plotting the receiver operating characteristic (ROC) curves. RESULTS At the calculated optimal cutoff for each of the examined parameters, the sensitivity ranged from 78% (for area under curve) up to 94% (for FWHM), the specificity ranged from 94% [for I2/I1% and area under curve] up to 100% (for FWHM), and the diagnostic accuracy ranged from 86% (for area under curve) up to 97% (for FWHM). The area under the ROC curves is greater than 0.95 for all of the investigated parameters, reflecting a highly accurate diagnostic performance. CONCLUSIONS The discussed tests offered a means to quantitatively evaluate the performance of the suggested breast tissue x-ray scattering characterization parameters. The performance results are promising, indicating that the evaluated parameters would be considered a tool for fast, on spot probing of breast cancer in excised tissue samples.

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.

Monte Carlo simulation of x-ray scattering for quantitative characterization of breast cancer

In the last decade there has been growing interest in the possibility of characterizing breast cancer using differences in the coherent x-ray-scattering profiles of normal and malignant tissues. To a great extent, characterization has depended on the differences in the peak positions of both tissues in addition to the overall profile which exhibits a distinctive sharp adipose peak in the case of a normal breast. In many excised tissue samples, breast cancer samples may be mixed with a variable percentage of other tissues which affect the shape of the x-ray-scattering profile and consequently the ability to characterize the tissue. Moreover, fibroglandular tissue produces a scattering profile showing an extent of similarity to breast cancer. The present study introduces a Monte Carlo simulation code capable of tracing photon transport inside a mixed two-component sample. The code is utilized to simulate and best fit x-ray-scattering profiles of the measured samples. This provides reliable breast tissue characterization in addition to a quantitative estimate of the percentage of each component in a given sample. It is expected that the present simulation would potentially enhance the characterization of breast cancer using the x-ray-scattering technique.

Analysis of low-angle x-ray scattering peaks from lyophilized biological samples

Low-angle x-ray scattering (LAXS) from lyophilized blood and its constituents is characterized by the presence of two peaks in the forward direction of scattering. These peaks are found to be sensitive to the variations in the molecular structure of a given sample. The present work aims to explore the nature of LAXS from a variety of lyophilized biological samples. It also aims to investigate the possibility that a certain biological macromolecule is responsible of the production of LAXS peaks. This is carried out through measurements of LAXS from complex biological samples and their basic constituents. Among the measured samples are haemoglobin (Hb), globin, haem, packed red blood cells, bovine albumin, egg albumin, milk, casein, glutamine, alanine, fat, muscle and DNA. A table containing some characteristic parameters of the LAXS profiles of these samples is also presented. Analysis of measured profiles shows that all lyophilized samples produce at least one relatively broad peak at a scattering angle around 10.35 degrees. The full width at half maximum (FWHM) of this peak varies considerably among the measured samples. Except for milk and casein. one additional peak at a scattering angle around 4.65 degrees is observed only in the LAXS profiles of proteins or protein-rich samples. This fact strongly suggests protein to be the biological macromolecule from which this characteristic peak originates. The same idea is further strengthened through discussion of some previous observations.

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.

Low-angle x-ray scattering from lyophilized blood constituents

The characteristic nature of low-angle x-ray scattering from biological samples and its dependence on molecular structure is a subject of increasing interest. In this work, low-angle x-ray scattering from lyophilized (freeze-dried) whole blood, haemoglobin (Hb), serum and red blood cell membranes is studied. The scattering profiles of these samples are found to be reproducible and characteristic. A number of characterization parameters are introduced, showing significant differences between the investigated samples. The sensitivity of the scattering profiles of whole blood, Hb and serum towards induced molecular level variations is examined after doses of gamma irradiation of 3, 6 and 9 Gy. The full width at half maximum (FWHM) of the second peak of scattering and the percentage ratio of amplitudes of the first and second peaks (I1/I2)% are found to be the parameters most sensitive to irradiation. For all irradiated samples, it is observed that the FWHM of the second peak is always greater than the control, while the ratio (I1/I2)% is always smaller than the control.

Characteristics of low-angle x-ray scattering from some biological samples.

Design of medical imaging devices based on the detection of low-angle coherent scattering is a subject of increasing interest. The technique is based on the differences in the distribution of photons coherently scattered from different body tissues. Coherent scattering is also useful in monitoring changes that may occur in a healthy tissue (e.g. carcinoma). In this work, low angle scattering properties of some tissues and tissue-equivalent materials are studied. Special care is given to the possibility of distinguishing between tissues of similar water content (e.g. muscle and blood). For this purpose, a Monte Carlo simulation is updated, introducing molecular form factor data, which include molecular interference effects. This program is used to simulate the angular distribution of scattered photons from two tissue-equivalent materials (lucite and water) and three biological samples (muscle, fat and blood). Simulation results agree well with previously measured angular distributions of scattered photons at 59.54 keV. Scattering from water and lucite is also measured at 8.047 keV. The effects of scattering geometry, sample thickness, incident photon energy and tissue type on the angular distribution of scattered photons are investigated. Results reveal the potential of measuring the full width at half maximum (FWHM) of the scattered photon distribution for tissue characterization. Energies up to 13 keV and sample thickness of 0.3 cm reported maximum differences between investigated samples. These conditions are expected to maximize the potential of using coherent scattering set-ups to monitor changes in biological samples even if their water contents are similar. Present results may act as a guide for the optimization of coherent scattering imaging systems.