Diagnostic utility of leptin and insulin-like growth factor binding protein-2 in hepatocellular carcinoma of diabetic and non-diabetic Egyptian patients

Purpose: To elucidate the possible diagnostic utility of adipokines and insulin growth factor binding proteins in hepatocellular carcinoma (HCC) diabetic subjects.Methods: Seventy five patients were divided equally into 3 groups as follows: healthy normal control (NC), non-diabetic hepatocellular carcinoma (HCC) and diabetic hepatocellular carcinoma (HCC-DM). Serum levels of leptin, insulin growth factor binding protein-2 (IGFBP-2) and alpha fetoprotein (AFP) were measured. Correlation and receiver operating characteristics (ROC) analysis was carried out.Results: HCC and HCC-DM groups showed changes in body mass index (BMI, p > 0.05 and p < 0.001 respectively), glucose, insulin, homeostatic model assessment-insulin resistance (HOMA-IR), liver function tests and AFP (p < 0.001). Leptin levels increased significantly in both HCC and HCC-DM (p < 0.001). Furthermore, IGFBP-2 showed significant increase in both groups (p < 0.001). Both leptin and insulin-like growth factor binding protein-2 (IGFBP-2) displayed significant positive correlation with AFP (p < 0.001). ROC analysis indicate different diagnostic accuracies for the tested markers for the various groups.Conclusion: Leptin and IGFBP-2 demonstrate significant potentials as diagnostic tools for HCC patients, especially diabetic cases, with IGFBP-2 displaying the highest diagnostic accuracy for HCC and HCC-DM groups.Keywords: Hepatocellular carcinoma, Diabetes mellitus, Leptin, Insulin-like growth factor-binding proteins-2, Adipokine

Expression of Hepatoma-derived growth factor family members in the adult central nervous system

BACKGROUND: Hepatoma-derived growth factor (HDGF) belongs to a polypeptide family containing five additional members called HDGF related proteins 1–4 (HRP-1 to -4) and Lens epithelial derived growth factor. Whereas some family members such as HDGF and HRP-2 are expressed in a wide range of tissues, the expression of others is very restricted. HRP-1 and -4 are only expressed in testis, HRP-3 only in the nervous system. Here we investigated the expression of HDGF, HRP-2 and HRP-3 in the central nervous system of adult mice on the cellular level by immunohistochemistry. In addition we performed Western blot analysis of various brain regions as well as neuronal and glial cell cultures. RESULTS: HDGF was rather evenly expressed throughout all brain regions tested with the lowest expression in the substantia nigra. HRP-2 was strongly expressed in the thalamus, prefrontal and parietal cortex, neurohypophysis, and the cerebellum, HRP-3 in the bulbus olfactorius, piriform cortex and amygdala complex. HDGF and HRP-2 were found to be expressed by neurons, astrocytes and oligodendrocytes. In contrast, strong expression of HRP-3 in the adult nervous system is restricted to neurons, except for very weak expression in oligodendrocytes in the brain stem. Although the majority of neurons are HRP-3 positive, some like cerebellar granule cells are negative. CONCLUSION: The coexpression of HDGF and HRP-2 in glia and neurons as well as the coexpression of all three proteins in many neurons suggests different functions of members of the HDGF protein family in cells of the central nervous system that might include proliferation as well as cell survival. In addition the restricted expression of HRP-3 point to a special function of this family member for neuronal cells

Overexpression of hepatoma-derived growth factor in melanocytes does not lead to oncogenic transformation

<p>Abstract</p> <p>Background</p> <p>HDGF is a growth factor which is overexpressed in a wide range of tumors. Importantly, expression levels were identified as a prognostic marker in some types of cancer such as melanoma.</p> <p>Methods</p> <p>To investigate the presumed oncogenic/transforming capacity of HDGF, we generated transgenic mice overexpressing HDGF in melanocytes. These mice were bred with mice heterozygous for a defective copy of the Ink4a tumor suppressor gene and were exposed to UV light to increase the risk for tumor development both genetically and physiochemically. Mice were analyzed by immunohistochemistry and Western blotting. Furthermore, primary melanocytes were isolated from different strains created.</p> <p>Results</p> <p>Transgenic animals overexpressed HDGF in hair follicle melanocytes. Interestingly, primary melanocytes isolated from transgenic animals were not able to differentiate <it>in vitro </it>whereas cells isolated from wild type and HDGF-deficient animals were. Although, HDGF^-/-/Ink4a^+/-mice displayed an increased number of epidermoid cysts after exposure to UV light, no melanomas or premelanocytic alterations could be detected in this mouse model.</p> <p>Conclusions</p> <p>The results therefore provide no evidence that HDGF has a transforming capacity in tumor development. Our results in combination with previous findings point to a possible role in cell differentiation and suggest that HDGF promotes tumor progression after secondary upregulation and may represent another protein fitting into the concept of non-oncogene addiction of tumor tissue.</p

Expression patterns and different subcellular localization of the growth factors HDGF (hepatoma-derived growth factor) and HRP-3 (HDGF-related protein-3) suggest functions in addition to their mitogenic activity.

HDGF (hepatoma-derived growth factor) and the HRPs (HDGF-related proteins) comprise a family of six proteins which display high identity in their N-terminus, but differ at the C-terminus. Here we investigate the patterns of expression of HDGF and HRP-3, by generating antisera specifically recognizing each growth factor. Whereas HRP-3 protein is expressed only in brain, HDGF can be found in a broad range of tissues, with highest levels in brain, testis, lung and spleen. The expression of HDGF and HRP-3 was found to be regulated during brain development, with highest levels around birth, followed by a decline until postnatal day 9. Interestingly, expression of HRP-3 increases again in adult brain. In situ hybridization and immunohistochemistry of cerebellar, cerebral and hippocampal brain slices showed that expression of both growth factors is not limited to areas of high proliferative activity. Both mRNAs and proteins are expressed in neuronal as well as glial cells. Immunocytochemistry of cultured neocortical neurons revealed that HDGF and HRP-3 can be found in the nucleus as well as the cytoplasm. HDGF is restricted to the neuronal soma, whereas HRP-3 can also be found in neurites. Thus the expression of HDGF and HRP-3 in differentiated cells, post-mitotic neurons and primary cultures of rat neocortex points to functions in brain that might not be limited to proliferation. In addition, their simultaneous expression in the same cell and their different subcellular localization in cultured neurons suggest different functions of HDGF and HRP-3 within single cells

Expression of Hepatoma-derived growth factor family members in the adult central nervous system-3

<p><b>Copyright information:</b></p><p>Taken from "Expression of Hepatoma-derived growth factor family members in the adult central nervous system"</p><p>BMC Neuroscience 2006;7():6-6.</p><p>Published online 23 Jan 2006</p><p>PMCID:PMC1363353.</p><p>Copyright © 2006 El-Tahir et al; licensee BioMed Central Ltd.</p>pective proteins in brain slices of adult mice. In all cases a part of the hippocampal region is shown. Double immunfluorescence demonstrates that HDGF (C, arrows) and HRP-2 (F, arrows) are expressed in cells positive for GFAP. In contrast no costaining of cells containing both GFAP as well as HRP-3 could be detected (I). Bars are 40 μm

Expression of Hepatoma-derived growth factor family members in the adult central nervous system-1

<p><b>Copyright information:</b></p><p>Taken from "Expression of Hepatoma-derived growth factor family members in the adult central nervous system"</p><p>BMC Neuroscience 2006;7():6-6.</p><p>Published online 23 Jan 2006</p><p>PMCID:PMC1363353.</p><p>Copyright © 2006 El-Tahir et al; licensee BioMed Central Ltd.</p>teins in brain slices of adult mice. Double stainings demonstrate that in contrast to HDGF and HRP-2, HRP-3 is not expressed in NeuN positive granular cells of the cerebellum. Distinct cells in the IGL detected by HRP-3 antibodies are most likely Golgi cells (I, arrowheads). In addition HRP-3 is also clearly expressed in the PCL and weakly in some cells of the MCL (I). MCL: molecular cell layer; PCL: purkinje cell layer; IGL: internal granular cell layer; WM: white matter. Bars are 80 μm

Expression of Hepatoma-derived growth factor family members in the adult central nervous system-8

<p><b>Copyright information:</b></p><p>Taken from "Expression of Hepatoma-derived growth factor family members in the adult central nervous system"</p><p>BMC Neuroscience 2006;7():6-6.</p><p>Published online 23 Jan 2006</p><p>PMCID:PMC1363353.</p><p>Copyright © 2006 El-Tahir et al; licensee BioMed Central Ltd.</p>cted to SDS-PAGE as described under material and methods. After blot transfer membrane was incubated with antibodies against the different HDGF family members or GAP-43 and actin as controls. Whereas HDGF is expressed to a similar extent in all four cell types, HRP-2 and HRP-3 show a more restricted expression pattern in neural cell cultures. Molecular weights of marker proteins in kiloDalton are given on the left

Expression of Hepatoma-derived growth factor family members in the adult central nervous system-4

<p><b>Copyright information:</b></p><p>Taken from "Expression of Hepatoma-derived growth factor family members in the adult central nervous system"</p><p>BMC Neuroscience 2006;7():6-6.</p><p>Published online 23 Jan 2006</p><p>PMCID:PMC1363353.</p><p>Copyright © 2006 El-Tahir et al; licensee BioMed Central Ltd.</p>espective proteins in brain slices of adult mice. In all cases fiber tracts in the brain stem are shown. Double immunfluorescence demonstrates that HDGF (C, arrowheads) and HRP-2 (F, arrowheads) are strongly expressed by cells also positive for CNPase. In contrast HRP-3 is only very weakly expressed by this cell type (I, arrowheads) when compared to other HRP-3 positive cells which most likely represent brain stem neurons (I, asterisks). Bars are 25 μm

Expression of Hepatoma-derived growth factor family members in the adult central nervous system-7

<p><b>Copyright information:</b></p><p>Taken from "Expression of Hepatoma-derived growth factor family members in the adult central nervous system"</p><p>BMC Neuroscience 2006;7():6-6.</p><p>Published online 23 Jan 2006</p><p>PMCID:PMC1363353.</p><p>Copyright © 2006 El-Tahir et al; licensee BioMed Central Ltd.</p>um of an adult mouse. To label the nuclei of all cells in the sections counterstaining with propidium iodide was performed (B,C and E,F). Double stained sections were used to calculate the percentage of cells positive for HDGF or HRP-3, respectively. Whereas HDGF is expressed in all cells, HRP-3 expression is much more restricted (for details see text). Cells labeled with arrows in D represent HRP-3 positive Purkinje cells. Asterisks in E mark most likely radial glia cells. MCL: molecular cell layer; PCL: purkinje cell layer; IGL: internal granular cell layer; Bars are 25 μm