Gypsogenin Battling for a Front Position in the Pentacyclic Triterpenes Game of Thrones on Anti-Cancer Therapy: A Critical Review-Dedicated to the Memory of Professor Hanaa M. Rady.

In the last decade, gypsogenin has attracted widespread attention from medicinal chemists by virtue of its prominent anti-cancer potential. Despite its late identification, gypsogenin has proved itself as a new anti-proliferative player battling for a frontline position among other classic pentacyclic triterpenes such as oleanolic acid, glycyrrhetinic acid, ursolic acid, betulinic acid, and celastrol. Herein, we present the most important reactions of gypsogenin via modification of its four functional groups. Furthermore, we demonstrate insights into the anti-cancer activity of gypsogenin and its semisynthetic derivatives and go further by introducing our perspective to judiciously guide the prospective rational design. The present article opens a new venue for a better exploitation of gypsogenin chemical entity as a lead compound in cancer chemotherapy. To the best of our knowledge, this is the first review article exploring the anti-cancer activity of gypsogenin derivatives.

MicroRNA-25 Exerts an Oncogenic Function by Regulating the Ubiquitin Ligase Fbxw7 in Hepatocellular Carcinoma.

BACKGROUND: MicroRNA (miRNA) expression abnormalities are implicated in tumor progression. Previous reports have indicated that microRNA-25 (miR-25) acts as a tumor suppressor or oncogene in diverse cancers. However, its molecular mechanisms in hepatocellular carcinoma (HCC) are still unclear. F-box and WD repeat domain 7 (Fbxw7) is a critical tumor suppressor and is one of the most important deregulated proteins of the ubiquitin-proteasome system in cancer. Our objective was to elucidate the role of miR-25 and Fbxw7 in HCC and to clarify the mechanism by which Fbxw7 is regulated. METHODS: Fbxw7 expression was estimated in 210 fixed paraffin-embedded HCC samples by immunohistochemistry, and miR-25 expression was evaluated in 142 frozen HCC tissue samples by quantitative real-time PCR. Oncogenic functions of miR-25 and its role in the regulation of Fbxw7 expression were assayed in vitro. RESULTS: miR-25 was overexpressed in HCC tissue compared with adjacent normal tissue and significantly correlated with a poorer prognosis. Moreover, it was inversely correlated with Fbxw7 expression in HCC tissues. Furthermore, miR-25 inhibition significantly reduced the proliferation, migration, and invasion of HCC cells in vitro. CONCLUSION: miR-25 may promote tumor progression in HCC patients by repression of Fbxw7 and could serve as a promising molecular target for HCC treatment.

New Biomarkers as Prognostic Factors for Cardiovascular Complications in Type 2 Diabetic Patients.

This study was initiated to explore some novel biomarkers like pro-inflammatory markers (chemerin and visfatin) and anti-inflammatory marker (omentin-1) as prognostic factors for cardiovascular complications in type 2 diabetic patients. Forty diabetic patients without cardiovascular disease, 40 diabetic patients with cardiovascular disease and twenty healthy control counterparts were included in this study. Serum chemerin, omentin-1 and visfatin levels were quantified. Receiver operating characteristic curve analysis was done to identify the cut off value for each marker. The mean serum level of chemerin was 57.65 ± 15.69 ng/l in diabetic patients versus 93.97 ± 26.62 ng/l for the cardio-diabetic ones (P < 0.0001). The mean serum level of omentin-1 was 8.77 ± 1.53 ng/ml in diabetic patients versus 1.76 ± 0.96 ng/ml for the cardio-diabetic ones (P < 0.0001). The mean level of visfatin was 1.44 ± 0.71 ug/l in diabetic patients versus 3.92 ± 3.32 ug/l for the cardio-diabetic ones (P < 0.0001). Chemerin and Visfatin levels were significantly enhanced in the cardio-diabetic patients with increasing C-reactive protein (CRP), triglycerides (TG), fasting blood glucose (FBG), micro-albumin and cholesterol. Omentin-1 level was significantly reduced in the cardio-diabetic patients with increasing CRP, TG, FBG, and cholesterol. It was observed that the area under curve for chemerin, omentin-1and visfatin was 0.877, 0.998 and 0.735, respectively. In conclusion, this study evidences that the measuring serum levels of chemerin, omentin-1 and visfatin may help in the prognosis of cardiovascular complications in type 2 diabetic patients.

Evaluation of urinary 8-hydroxy-2-deoxyguanosine level in experimental Alzheimer's disease: Impact of carvacrol nanoparticles.

The present study aimed to compare the effect of carvacrol essential oil and carvacrol nanoemulsion against experimental Alzheimer's (AD). Forty male albino rats were used and divided into four groups as follow: control, AlCl3 induced AD, carvacrol oil treated and carvacrol nanoemulsion treated groups. Brain nor-epinephrine, serotonin and dopamine were analyzed by high performance liquid chromatography (HPLC). Levels of brain Thiobarbituric acid-reactive substances (TBARS), Superoxide dismutase (SOD), reduced glutathione (GSH), cholinesterase, and advanced oxidation protein product (AOPP) were evaluated. Urinary 8-hydroxyguanosine (8-OHdG) level was evaluated by HPLC. Brain Cyclooxygenase 1 and 2 (COX 1and 2) were analyzed by immunohistochemistry. AD induced by AlCl3 in rats was depicted by the significant increase in the neurotransmitters levels which is accompanied with high degree of oxidative stress that was revealed in the elevated level of urinary 8-OHdG along with significant elevation in AOPP, TBARS, and cholinesterase levels and a significant decrease in SOD and GSH; these results are confirmed by immunohistochemistry analysis of COX 1 and 2. On the other hand, the treatment with carvacrol oil and carvacrol nanoemulsion were capable of mitigate effects mediated by AlCl3 administration in treated rats. While the treatment with both approached succeeded to retract the negative impact of AlCl3; but the effect of carvacrol nanoemulsion was more notable than the essential oil. Carvacrol oil and carvacrol nanoemulsion were eminent to overturn AlCl3 induced brain AD which could be imputed to antioxidant and anti-inflammatory capabilities of carvacrol to alter oxidative stress effect. In extension; carvacrol nanoemulsion were evident to give more effective and efficient way in carvacrol delivery to pass through blood brain barriers and ameliorate brain changes.

Role of mesenchymal stem cells versus angiotensin converting enzyme inhibitor in kidney repair.

AIM: The current study sought to clarify the role of bone marrow derived mesenchymal stem cells (BM-MSCs) and adipose tissue derived mesenchymal stem cells (AD-MSCs) in repressing nephropathy in the experimental model. Moreover, the aim of this work was extended to compare between stem cells role and angiotensin converting enzyme inhibitor in kidney repair. METHODS: Isolation and preparation of MSCs culture, flow cytometry using CD34, CD44 and CD105 cell surface markers, biochemical analyses for determination of serum creatinine, urea, transforming growth factor ß (TGF-ß), cystatin C (CYS-C) and urinary N-Acetyl-ß-D-Glucosaminidase (UNAG), and histopathological investigation of kidney tissue sections were performed. RESULTS: The results of the present study revealed that single intravenous infusion of MSCs either derived from bone marrow or adipose tissue was able to enhance renal reparative processes through significantly decreased serum creatinine, urea, TGF-ß and CYS-C levels as well as UNAG level and significantly increase glomerular filtration rate. Additionally, the histopathological investigations of kidney tissues showed that MSCs have significant regenerative effects as evidenced by the decrease in focal inflammatory cells infiltration, focal interstitial nephritis and congested glomeruli as well as degenerated tubules. CONCLUSION: The current data provided distinct evidence about the favourable impact of AD-MSCs and BM-MSCs in attenuation of cyclosporine-induced nephropathy in rats through their ability to promote functional and structural kidney repair via transdifferentiation.

Chromatographic determination of some biomarkers of liver cirrhosis and hepatocellular carcinoma in Egyptian patients.

Metabolomics has been shown to be an effective tool for disease diagnosis, biomarker screening and characterization of biological pathways. A total of 140 subjects were included in this study; urine metabolomes of patients with liver cirrhosis (LC, n = 40), patients with hepatocellular carcinoma (HCC; n = 55) and healthy male subjects (n = 45) as a control group were studied. Gas chromatography/mass spectrometry-based urine metabolomics profiles were investigated for all participants. Diagnostic models were constructed with a combination of marker metabolites, using principal components analysis and receiver operator characteristic curves. A total of 57 peaks could be auto-identified of which 13 marker metabolites (glycine, serine, threonine, proline, urea, phosphate, pyrimidine, arabinose, xylitol, hippuric acid, citric acid, xylonic acid and glycerol) were responsible for the separation of HCC group from healthy subjects. Also, eight markers metabolites (glycine, serine, threonine, proline, citric acid, urea, xylitol and arabinose) showed significant differences between the LC group and healthy subjects. No significant difference was detected between HCC and LC groups regarding all these metabolites. Metabolomic profile using GC-MS established an optimized diagnostic model to discriminate between HCC patients and healthy subjects; also it could be useful for diagnosis of LC patients. However, it failed to differentiate between HCC and LC patients.

Acetylcholinesterases from entomopathogenic nematode Heterorhabditid bacteriophora: Susceptibility to insecticides and immunological characteristics.

Acetylcholinesterases (AChEs) from the infective juveniles (IJs) of entomopathogenic nematode (EPN) have been investigated with respect to their susceptibility to insecticides and immunological characteristics, aiming at nominating the most compatible insecticide(s) to be used in conjunction with the most insecticide-tolerant EPN strain before incorporation in integrated pest management (IPM) programs. The inhibition kinetics of two purified AChE isoenzymes, AChEAII and AChEBI isolated from Heterorhabditid bacteriophora EM2 strain, by different insecticides revealed that the insensitivity to inhibition by such insecticides could be arranged in a descending order as; methomyl>carbofuran>acetamiprid>oxamyl>malathion. Except for malathion, the insecticides competitively inhibited AChEs with Ki values ranging from 0.1 to 15mM and IC50 values from 1.25 to 23mM. The two AChE isoforms are several folds less sensitive to inhibition by methomyl and carbofuran compared to those previously reported for other insect species. AChEBI was used as an immunogen to raise anti-AChEBI antisera in rabbits. The prepared antisera cross-reacted with AChEs of five different heterorhabditid nematode strains implying the presence of common epitopes shared along all the examined strains. Such studies could aid in the rational selection of the compatible insecticide(s) and the prepared polyclonal anti-AChE antisera would be a valuable immunodiagnostic tool for evaluating the most insecticide-tolerant EPN strain(s) in IPM programs.

Curcumin: a unique antioxidant offers a multimechanistic approach for management of hepatocellular carcinoma in rat model.

This study was designed to investigate the role of curcumin against hepatocellular carcinoma (HCC) induced in rats. Forty rats were divided into five groups. Group (1) was negative control. Groups (2), (4), and (5) were orally administrated N-nitrosodiethylamine for HCC induction, then group (2) was left untreated, and group (4) was treated orally with curcumin, while group (5) was intraperitoneally injected with doxorubicin. Group (3) was served as curcumin control group. Serum alpha-fetoprotein, alpha L-fucosidase and vascular endothelial growth factor levels were analyzed. Gamma glutamyl transferase (GGT) and heat shock protein gp96 (HSPgp96) gene expressions were detected by RT-PCR. The immunohistochemical analysis of proliferating cell nuclear antigen (PCNA) and Ki-67 expressions was performed. Apoptosis was detected using DNA fragmentation assay. Also, histological investigation of liver tissue was achieved. Untreated HCC group showed significant elevation in the studied biochemical markers and significant upregulation in GGT and HSPgp96 gene expression as well as marked increase in PCNA and Ki-67 expression. Furthermore, this group revealed no DNA fragmentation. Histological investigation of liver tissue sections in HCC group revealed a typical anaplasia. On the other hand, the curcumin-treated group showed a significant depletion in the studied tumor markers and a significant downregulation in GGT and HSPgp96 gene expression. Also, this group displayed remarkable decrease in PCNA and Ki-67 expression. Moreover, this group revealed an obvious DNA fragmentation. Interestingly, treatment with curcumin showed remarkable improvement in the histological features of liver tissue. This study revealed the promising therapeutic role of curcumin against hepatocellular carcinoma owing to its antiangiogenic, antiproliferative, and apoptotic effects.

Effects of smoking on the oxidant/antioxidant balance and the blood lipids in pesticide sprayers.

The present study was conducted on 80 pesticide male sprayers (42 nonsmokers and 38 smokers). Our aim was to estimate the smoking effects on blood lipids and oxidant/antioxidant status in pesticide sprayers. Results revealed that cholesterol, low-density lipoprotein (LDL) and glutathion peroxidase (GPx) enzyme were significantly higher in the 38 smoker sprayers than in the 42 nonsmoker sprayers. Cholesterol and LDL were correlated with smoking index and high-density lipoprotein (HDL), superoxide dismutase (SOD) enzyme and zinc (Zn) were inversely correlated with duration of pesticides' exposure. In nonsmokers, LDL and cholesterol were negatively correlated with SOD and correlated with malondialdehyde (MDA), and cholesterol was negatively correlated with Zn. HDL was negatively correlated with MDA in all the sprayers, but was correlated with GPx in smokers and with Zn in nonsmokers. In smokers, LDL was negatively correlated with GPx, HDL was negatively correlated with MDA and triglycerides and very-low-density lipoprotein were negatively correlated with Zn. MDA was negatively correlated with SOD, GPx and Zn. Smoking and pesticide exposure could be responsible for hyperlipidemia and oxidative stress. Therefore, improvement in the antioxidant status is mandatory for pesticide sprayers especially the ones who smoke.

Development of a novel score for early detection of hepatocellular carcinoma among high-risk hepatitis C virus patients.

Hepatocellular carcinoma (HCC) is often diagnosed at advanced stage where effective therapies are lacking. Identification of new scoring system is needed to discriminate HCC patients from those with chronic liver disease. Based on the link between vascular endothelial growth factor (VEGF) and HCC progression, we aimed to develop a novel score based on combination of VEGF and routine laboratory tests for early prediction of HCC. VEGF was assayed for HCC group (123), liver cirrhosis group (210), and control group (50) by enzyme-linked immunosorbent assay (ELISA). Data from all groups were retrospectively analyzed including α-fetoprotein (AFP), international normalized ratio (INR), albumin and platelet count, transaminases, and age. Areas under receiving operating curve (ROC) were used to develop the score. A novel index named hepatocellular carcinoma-vascular endothelial growth factor score (HCC-VEGF score) = 1.26 (numerical constant + 0.05 × AFP (U l(-1)) + 0.038 × VEGF (ng ml(-1)) + 0.004 × INR - 1.02 × albumin (g l(-1)) - 0.002 × platelet count × 10(9) l- (1) was developed. HCC-VEGF score produce area under ROC curve of 0.98 for discriminating HCC patients from liver cirrhosis with sensitivity of 91 % and specificity of 82 % at cutoff 4.4 (i.e., less than 4.4 considered cirrhosis and greater than 4.4 considered HCC). Hepatocellular carcinoma-VEGF score could replace AFP in HCC screening and follow up of cirrhotic patients.

A novel discriminant score based on tumor-associated trypsin inhibitor for accurate diagnosis of metastasis in patients with breast cancer.

Invasion and metastasis of solid tumors require proteolytic enzymes for degradation of the basal membrane and extracellular matrix. Currently, there are no reliable methodologies to predict the risk for metastatic disease. In this context, our aim has been focused on the development of a noninvasive score based on tumor-associated trypsin inhibitor (TATI) for the assessment of metastasis in patients with breast cancer. TATI, trypsin, and soluble epidermal growth factor receptor (sEGFR) were assayed by enzyme-linked immunosorbent assay. CA 15.3 serum level was assayed by microparticle enzyme immunoassay in 265 patients with breast cancer. Statistical analyses were performed by logistic regression and receiver operating characteristic analysis curves. Using multivariate discriminant analysis, a score is selected based on absolute values of the four biochemical markers: TATI-metastatic breast cancer score (TATI-MBCS) = [0.03 × CA 15.3 (U/L) + 0.039 × TATI (ng/ml) + 0.04 × trypsin (ng/ml) + 0.023 × sEGFR (ng/ml) - 6.49 (numerical constant)]. This function correctly classified 84% of metastatic breast cancer at cutoff value = 0.62 (i.e., greater than 0.62 indicates patients with metastatic breast cancer and less than 0.62 indicates patients with nonmetastatic breast cancer). In conclusion, TATI-MBCS is a novel, noninvasive, and simple score which can be applied to discriminate patients with metastatic breast cancer.

Biochemical evaluation of hyaluronic acid in breast cancer.

BACKGROUND: The latest experimental studies on human cancer diseases have observed the bioactive role of hyaluronic acid (HA) during carcinogenesis. HA is a component of the extra-cellular matrix (ECM). It is closely correlated with tumor cell growth, proliferation, and metastasis. The present study aimed to evaluate the biochemical role of HA and its degrading enzymes and products in breast cancer (BC) patients under therapy treatment. METHODS: An ELISA method was used to determine HA levels and standard spectrophotometric techniques were used to estimate the activities of HA degrading enzymes hyaluronidase (HAS), N-acetyl-beta-D-glucosminidase (NAG), and beta-glucuronidase (beta-Glu) and the concentration of both glucoseamine (G-Amine) and glucuronic acid (GA) as degrading products in blood sera of 50 BC patients before and after chemotherapy treatment and in blood sera of 40 healthy women as controls. Statistical analyses were performed by a statistical package for social sciences (SPSS, version 15.0). RESULTS: Elevated serum HA levels, increased HAS, NAG, and beta-Glu activities and high concentrations of G-Amine and GA were significantly found (p < 0.001) in patients before treatment compared to controls. After all BC patients had received the first chemotherapy course, HA and its previous degrading parameters were significantly decreased (p < 0.001) in post-treated patients compared to pre-treated patients. CONCLUSIONS: Hyaluronic acid and its degrading enzymes and products can be considered a biomarker for early detection of recurrent disease and also for monitoring the effective therapeutic follow up of BC patients.

Clinical Utility of Cytokeratins for Accurate Diagnosis of Hepatocellular Carcinoma Among Hepatitis C Virus High-Risk Patients.

OBJECTIVES: Hepatocellular carcinoma (HCC) is a primary malignancy of the liver and a global health problem. It is often diagnosed at advanced stage where hopeless for effective therapies. Identification of more reliable biomarkers for early detection of HCC is urgently needed. Cytokeratins are a marker of hepatic progenitor cells and act as a key player in tumor invasion. Herein, we sought to develop a novel score based on the combination of cytokeratin 18 (CK18) and cytokeratin 19 (CK19) with routine laboratory tests for accurate detection of HCC. MATERIAL & METHODS: Serum CK18, CK 19, α-fetoprotein, albumin and platelets count were assayed in HCC patients (75), liver cirrhosis patients (55) and healthy control (20). Areas under receiving operating curve (AUCs) were calculated and used for construction on novel score. A novel score named CK-HCC = CK 19 (ng/ml)×0.001+ CK18 (ng/ml)×0.004 + AFP (U/L)×5.4 - Platelets count (×109)/L×0.003 - Albumin (g/L)×0.27-36 was developed. CK-HCC score produces AUC of 0.919 for differentiating patients with HCC from those with liver cirrhosis with sensitivity and specificity of a cut-off 1.3 (i.e., less than 1.3 the case is considered cirrhotic, whereas above 1.3 it is considered HCC. CONCLUSION: CK-HCC score could replace AFP during screening of HCV patients and early detection of HCC.

Diagnostic Performance of Epithelial Cell Adhesion Molecule for Early Detection of Hepatocellular Carcinoma Among HCV High-Risk Patients.

OBJECTIVE: Hepatocellular carcinoma (HCC) is often diagnosed at advanced stage where hopeless for effective therapies. Identification of more reliable biomarkers for early detection of HCC is urgently needed. Circulating tumor cells (CTCs) represent a unique liquid biopsy carrying comprehensive biological information of the primary tumor. Herein, we sought to develop a novel score based on the combination of the most significant CTCs biomarkers with routine laboratory tests for accurate detection of HCC. MATERIAL & METHODS: Epithelial cell adhesion molecule (EpCAM), α-fetoprotein, albumin, and platelets count were assayed in HCC patients (98), liver cirrhosis patients (77). Areas under receiving operating curve (AUCs) were calculated and used for construction on novel score. RESULTS: A novel score named EpCAM-HCC = AFP (U/L) × 0.11 - Albumin (g/dl) × 1.5 + EpCAM % × 2.9 - Platelets count (×109)/L× 0.75 - 93. EpCAM-HCC score produce AUC of 1 for differentiate patients with HCC from those with liver cirrhosis with sensitivity and specificity of a cut-off 1.7 (i.e., less than 1.7 the case is considered cirrhotic, whereas above 1.7 it is considered HCC. CONCLUSION: EpCAM-HCC score could replace AFP during screening of HCV patients and early detection of HCC.

Circulating Tumor Cells in Breast Cancer: A Step Toward Precision Medicine for Real-Time Monitoring of Metastasis.

BACKGROUND/AIMS: Tumor metastasis involves the dissemination of malignant cells into the basement membrane and vascular system contributes to the circulating pool of these markers. In this context our aim has been focused on development of a non-invasive score based on degradation of glycosaminoglycans in the extracellular matrix for assessment of metastasis in patients with breast cancer. Circulating tumor cells (CTCs) represent a unique liquid biopsy carrying comprehensive biological information of the primary tumor. Herein, we sought to develop a novel score based on the combination of the most significant CTCs biomarkers with and routine laboratory tests for accurate detection of Metastases in patients with breast cancer. MATERIAL & METHODS: Cytokeratin 18 (CK18), Cytokeratin 19 (CK19) and CA15.3 were assayed in metastatic breast cancer patients (88), non-metastatic breast cancer patients (129) and healthy control (32). Areas under receiving operating curve (AUCs) were calculated and used for construction on novel score. A novel score named CTC-MBS = CA15.3 (U/L) × 0.08 + CK 18 % × 2.9 + CK19 × 3.1. CTC-MBS score produces AUC of 1 for differentiate patients with metastatic breast cancer from those with non-metastatic breast cancer with sensitivity and specificity of a cut-off 0 (i.e., less than 0 the case is considered metastatic, whereas above 0 it is considered non-metastatic. CONCLUSION: CTC-MBS score is a novel, non-invasive and simple can applied to discriminate patients with metastatic breast cancer and could replace CA15.3 during screening and follow-up of breast cancer patients.

Discriminant function based on parameters of hyaluronic acid metabolism and nitric oxide to differentiate metastatic from non-metastatic colorectal cancer patients.

Colorectal cancer (CRC) is one of the most common causes of cancer-related deaths worldwide. Because there is currently no useful serological marker for metastatic colorectal cancer, the search for simple biomarkers for colorectal cancer diagnosis and prognosis is needed. Hyaluronic acid level was determined by ELISA; in addition to its degrading enzymes, degradation products and nitric oxide were determined by standard techniques in 185 CRC patients with and without metastases. Statistical analyses were performed by logistic regression and receiver-operating characteristic (ROC) curves. The multivariate discriminate analysis (MDA) selects a function based on absolute values of six biochemical markers; score = [-0.62 (numerical constant) + hyaluronic acid (pg/l) × 0.002 + hyaluronidase (mg N-acetyl glucosamine/ml/18 h) × 0.009-ß-glucuronidase (µmol/ml/min) × 0.07 + N-acetyl-ß-D-glucosaminidase (µmol/ml/min) × 0.019-glucuronic acid (µg/dl) × 0.001 + nitric oxide (µmol/l) × 0.01]. The selected MDA function correctly classified 92% of the metastatic CRC patients at a discriminate cut-off score = 0.24 (i.e., less than 0.24 indicated patients with non-metastatic colon cancer, and greater than 0.24 indicated patients with metastatic colon cancer with high degrees of sensitivity (100%) and specificity (93%)). The positive predictive and negative predictive values were also high (81% and 85%, respectively). Colorectal cancer patients can be simply and efficiently classified into metastatic or non-metastatic using their MDA score.

In vivo Study of a Newly Synthesized Chromen-4-one Derivative as an Antitumor Agent against HCC.

BACKGROUND: Chromenes are a wide group of natural compounds that can be synthesized chemically. The chromen-4-one nucleus acts as a skeleton for varieties of additional active groups that makes the chromene activity vary between antioxidant and anti-inflammatory agents. In the present study, a newly synthesized chromene compound exhibits different behaviors other than anti-inflammatory and antioxidant activities that it is the first time that a member of chromen-4-one compound can control the cancer progress. Inflammation is the first step in tumor development where the severity grade can potentiate tumor growth and progression. In many tumors, pro-inflammatory genes record high expression level such as tumor necrosis factor (TNF-α) and vascular endothelial growth factors (VEGF). These pro-inflammatory factors act as rate limiting steps in tumor initiation, and controlling its expression acts as an early therapeutic way to control the tumor proliferation. The chromone derivatives have biological activities such as anti-inflammatory and anti-tumor activity. METHODS: In the present study, hepatocellular cancer (HCC) induced by diethylnitrosamine (DEN) in rats and then treated with the new chromene derivative and the parameters TNF-α, VEGF, p53, Cyt C, MMP-9, Bcl2, and Bax were measured. RESULTS: The treatment strategy Ch compound is to downregulate pro-inflammatory gene expression of early genes as TNF-α as well as VEGF and subsequently control other factors such as p53, Cyt C, and MMP-9. Also, retrieve the balance between Bcl2 and Bax proteins in DEN-induced HCC in rats. CONCLUSION: The ability of the new Ch derivative to control the primary initiators of HCC such as TNF-α offers this derivative an anti-tumor activity and encourages further researches to follow and monitor its effect on the molecular level.

Diagnostic Performance of Circulating Tumor Cells for Predicting of Hepatocellular Carcinoma in Hepatitis C Virus-High Risk Patients: Role of Liquid Biopsy.

PURPOSE: Hepatocellular carcinoma (HCC) is a primary malignancy of the liver and a global health problem. It is often diagnosed at advanced stage where hopeless for effective therapies. Identification of more reliable biomarkers for early detection of HCC is urgently needed. circulating tumor cells (CTCs) represent a unique liquid biopsy carrying comprehensive biological information of the primary tumor. Herein, we sought to develop a novel score based on the combination of the most significant CTCs biomarkers with and routine laboratory tests for accurate detection of HCC. METHODS: Cytokeratin 18 (CK18), Cytokeratin 19 (CK19), albumin, platelets count, and α-fetoprotein were assayed in HCC patients (42), liver cirrhosis patients (83) and healthy control (20). RESULTS: Areas under receiving operating curve (AUCs) were calculated and used for construction on novel score. A novel score named HCC-CTCs = AFP (U/L) × 0.08 - Albumin (g/dl) × 84 + CK 18 % × 2.9 + CK19 × 3.1- Platelets count (×109)/L× 0.75- 510. HCC-CTCs score produce AUC of 1 for differentiate patients with HCC from those with liver cirrhosis with sensitivity and specificity of a cut-off 0. CONCLUSIONS: HCC-CTCs score could replace AFP during screening of HCV patients and early detection of HCC.

Promoter hypermethylation of RASSF1A, MGMT, and HIC-1 genes in benign and malignant colorectal tumors.

Hypermethylation at the promoter region is an important epigenetic mechanism underlying the inactivation of tumor suppressor genes and frequently occurs as an early event in the development of different types of cancer including colorectal carcinoma (CRC). The aim of the present study is the detection of methylation status for some tumor suppressor genes including RASSF1A, MGMT, and HIC-1 in both cancerous and precancerous lesions of colorectal mucosa to evaluate the possibility of developing epigenetic biomarker for early detection of Egyptian CRC. Tissue biopsy was collected from 72 patients (36 CRC, 17 adenomatous polyps, and 19 ulcerative colitis), and in addition, adjacent normal-appearing tissues were collected as control. Promoter hypermethylation status for RSSAF1A, MGMT, and HIC-1 genes was detected after isolation of genomic DNA from the tissues samples using methylation-specific PCR technique. High frequency of methylation at MGMT, RASSFA, and HIC-1 was detected in CRC patients (25%, 47.2%, and 41.7% respectively). The highest methylation detected in adenomatous polyps patients was in MGMT gene (47.1%) followed by 35.3% for HIC-1 and only 5.9% for RASSF1A gene. HIC-1 gene exhibited highest frequency of methylation in ulcerative colitis patients (57.8%) whereas it was 26.3% for both RASSF1A and MGMT genes. A nonsignificant association was recorded between the methylation status in different genes examined with the clinicopathological factors except the association between methylation at RASSF1A gene with gender (p=0.005), and it was significant. In conclusion, aberrant hypermethylation at promoter region of RASSFA, MGMT, and HIC-1 genes is involved in Egyptian CRCs. Hypermethylation of MGMT and HIC-1 genes plays an important role in the initiation of disease especially ulcerative colitis-carcinoma pathway.

Development of novel score based on Angiogenic panel for accurate diagnosis of hepatocellular carcinoma among hepatitis C virus high-risk patients.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is a primary malignancy of the liver and a global health problem. It is often diagnosed at advanced stage where hopeless for effective therapies. Identification of more reliable biomarkers for early detection of HCC is urgently needed. HCC is identified with hyper-vascularity feature. Herein, we sought to develop a novel score based on the combination of the most significant angiogenic biomarkers with and routine laboratory tests for accurate detection of HCC. MATERIAL & METHODS: Angiopoietin II, copper, nitric oxide, albumin, platelets count and α-fetoprotein were assayed in HCC patients (75), liver cirrhosis patients (50) and healthy control (20). Areas under receiving operating curve (AUCs) were calculated and used for construction on novel score. A novel score named HCC-AngioScore = AFP (U/L) Albumin (g/dl) × 5.4 + Angiopoietin (ng/ml) × 0.001 + Copper (mg/dl) × (-0.004) + Platelets count (×109)/L × 0.003 + Nitric oxide (µ mol/L) × 0.27-36 was developed. HCC-AngioScore produce AUC of 0.919for differentiate patients with HCC from those with liver cirrhosis with sensitivity and specificity of a cut-off 0 (i.e., less than 0 the case is considered cirrhotic, whereas above 0 it is considered HCC. CONCLUSION: HCC-AngioScore could replace AFP during screening of HCV patients and early detection of HCC.