Browsing by Author "Bakkar, Ashraf"

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THE BACILLUS CALMETTE-GUéRIN DERIVED PURIFIED PROTEIN (PPD) POTENTIATES IN-VITRO ANTI-CANCER ACTIVITY OF CERASTES CERASTES SNAKE VENOM IN COLON AND PROSTATE CANCER CELLS
(Inventi, 2017-06) Sabatier, Jean-Marc; Shebl, Rania I; Bakkar, Ashraf; Mohamed, Aly Fahmy; Ayman, Mohamed
Prostate and colon cancer represent a major health problem worldwide. In the present study, we evaluated the anticancer properties and cytotoxicity of Cerastes-cerastes (CC) snake venom on colon (Caco-2) and prostate (PC-3) cancer cells after their pretreatment with variable concentrations of Bacillus Calmette-GuÃ©rin (BCG) derived purified protein derivative (PPD). We monitoned the cell cycle arrest profile and specific cellular apoptosis markers (i.e. pro- and anti-apoptotic genes P53, Bax and Bcl-2 in CC- and BCG/PPD-pretreated cells using real time PCR. The cytotoxicity was determined by using MTT assay. Our data show that 24 h-treatment of cancer cells with CC venom induced a concentration-dependent cytotoxicity with IC50 values of 60 (Caco-2 cells) and 81 (PC-3 cells) Î¼g/ml. Interestingly, addition of BCG/PPD at 25 and 50 Î¼g/ml markedly increased the CC venom-induced toxicity on cancer cells, with IC50 values of 1.04 and 0.59 Î¼g/ml for Caco-2 (up to 102-fold increase) or 2.78 and 0.70 Î¼g/ml for PC-3 cells (up to 116-fold increase). By analyzing the cell cycle arrest and related gene expression pattern, the main phase of cell cycle arrest was found to be G2/M in both cell lines. An S-phase arrest was also observed in PPD pretreated colon Caco-2 cell line to a greater extent than that observed in cells only treated with CC venom. Up regulation of proapoptotic and down regulation of anti-apoptotic genes in PPD pretreated cells were significantly enhanced as compared to cells treated with CC venom alone. In this study, we suggest that PPD -via its synergistic action with the CC venom-might be used as an enhancer of the anti-cancer properties of CC venom.
COMPARISON OF DIFFERENT FERMENTATION PARAMETERS OF PASTEURELLA MULTOCIDA ON THE DRY CELL MASS FOR THE PREPARATION OF FOWL CHOLERA VACCINE
(2016-12) Abulmagd, Shaimaa M; Bakkar, Ashraf; Shaker, Lamiaa S; Khaled, Abdel Rahman
Fowl cholera is a contagious bacterial disease of domesticated and wild avian species caused by infection with Pasteurellamultocida. This study was undertaken to investigate the effect of some different parameters as pH and agitation, air with DO (Dissolved oxygen) cascade to increase the production of dry cell mass from the fermentation of Pasteurellamultocida . These different kinetic parameters were carried out in three cultures containing two litters of Brain Heart Infusion broth media in 5 L fermentor (New Brunswick). The first culture (A) conditions were ; at 37 ºC, air flow 0.5 L/min, agitation frequency 90 rpm, dissolved oxygen was 80% and adjustment pH with 1 N NaOH, culture (B) was carried out under the same conditions with no pH adjustment. In addition, culture (C) was carried out with Agitation/Air/DO cascade, the set point of agitation was 90- 200 rpm, air flow 0.5-2 L/min. Culture A gave the highest optical density (OD) compared to culture B and culture C. The values of OD were 2.1, 1.7 and 1.5 respectively. Also, the highest dry cell mass (3.1 g/L), (2.7 g/L) were obtained in culture A and culture B respectively, but the lowest dry cell mass (2.2 g/L) was obtained from culture C with the agitation, air with DO cascade. The present study concluded that it adjusting pH, using low air flow and low agitation gives the highest yield of dry cell mass.
Elevated physiological levels of folic acid can increase in vitro growth and invasiveness of prostate cancer cells
(Blackwell Publishing Ltd, 2012) F Petersen, Lars; T Brockton, Nigel; Bakkar, Ashraf; Liu, Shuhong; Wen, Jing; M Weljie, Aalim; A Bismar, Tarek
Evidence has emerged identifying folic acid supplementation as a potential risk factor for cancer development or progression. Long‐term folic acid supplementation has been shown to increase the risk of prostate cancer development by three‐fold. Sarcosine is a byproduct of folate metabolism and has been proposed as a biomarker for aggressive prostate cancer phenotypes. We looked at the effects of physiologically relevant levels of folic acid on in vitro prostate cancer cell growth and invasion, and demonstrated that higher levels can have the effect of increasing both of these biological processes. We also show that these changes toward a more aggressive phenotype are not linked to increased sarcosine levels, however other metabolic pathways may be involved
From electrons to cancer : Redox shift as a driving force of tumorigenesis
(Elsevier, 2023-11) Attal, Romain; Bakkar, Ashraf; Bouillaud, Frederic; Devin, Anne; Henry, Marc; Ponti´e, Maxime; Radman, Miroslav; Schwartz, Laurent
Cancer cells are very diverse but mostly share a common metabolic property: they are strongly glycolytic even though oxygen is available. Herein, the metabolic abnormalities of cancer cells are interpreted as modifications of the electric currents in redox reactions. A lower current in the electron transport chain, an increase of the concentration of reduced cofactors and a partial reversal of the tricarboxylic acid cycle are physical characteristics of several forms of cancer. The existence of electric short-circuits between oxidative branches and reductive branches of the metabolic network argue in favor of an electronic approach of cancer in the nanoscopic scale. These changes of electron flows induce a pseudo-hypoxia and the Warburg effect through succinate production and divert electrons from oxygen to biosynthetic pathways. This new look at cancer may have potential therapeutic applications.
Gefitinib Inhibits the Growth and Invasion of Urothelial Carcinoma Cell Lines in which Akt and MAPK Activation Is Dependent on Constitutive Epidermal Growth Factor Receptor Activation
(American Association for Cancer Research, 2006) Nicolle, Gaëlle; Daher, Ahmed; Maillé, Pascale; Vermey, Marcel; Loric, Sylvain; Bakkar, Ashraf; Wallerand, Hervé; Vordos, Dimitrios; Vacherot, Francis; Gil Diez De Medina, Sixtina; C Abbou, Claude; Van der Kwast, Theodore; Thiery, Jean-Paul; Radvanyi, François; K Chopin, Dominique
Abnormally high levels of epidermal growth factor receptor (EGFR) protein are associated with advanced tumor stage/grade. The objective of this study was to evaluate the effects of the specific EGFR tyrosine kinase inhibitor gefitinib on activation of the Akt and mitogen-activated protein kinase (MAPK) pathways in human urothelial cell carcinoma (UCC) cell lines and to identify potential markers of gefitinib responsiveness in biopsy samples of UCC.
Grape Seed Extract Induces G2/M Cell Cycle Arrest and Apoptosis Via Generation of Reactive Oxygen Species in Breast and Colon Cancer Cell lines
(Inventi, 2017) Sabatseir, Jean Marc; Shebl, Rania Ibrahim; Bakkar, Ashraf; Mohamed, Aly Fahmy; Yaseen, Reem A
Grape seed as a fruit waste was found to have medicinal potentials, specially its procyanidine containment. The present work aimed to investigate the anticancer potential against two of the mostly spread cancers worldwide namely breast and colon cancers. Data recorded revealed that grape seed extract (GSE) demonstrated a dose dependent cytotoxic potential with an IC50 values of 148.5 and 190.2 Î¼g/ml for CaCo-2 and MCF-7 respectively. Gene expression pattern of apoptosis related genes revealed that GSE stimulates a p53-independent apoptotic pathway which was associated with G2/M phase arrest (pË‚0.05). The elevated level of reactive oxygen species (ROS) in the order of 28.5% and 40.8% in CaCo-2 and MCF-7, respectively suggested that GSE is involved also in initiating the intrinsic pathway of apoptosis. These findings focus on the potential of using GSE as a multi-targeted cancer therapy to overcome the problem of resistance to current treatments.
Interrogation of ERG gene rearrangements in prostate cancer identifies a prognostic 10‐gene signature with relevant implication to patients' clinical outcome‏
(wiley online library, 2014-02) Alhajj, Reda; Mucci, Lorelei A; Dolph, Michael; Liu, Shuhong; Al‐Mami, Amal; Bakkar, Ashraf; Gerke, Travis; Teng, Liang Hong; Petersen, Lars F; Alshalalfa, Mohammed; Bismar, Tarek A
Keywords ERG rearrangements, Gleason score, molecular pathways, ERG-like gene signature, prostate cancer, prognosis
Khalas date flavonoids inhibited cell viability, induced apoptosis and expression of the pro-autophagy LC3-B gene in human hepatocellular carcinoma cells (HepG2)
(Taylor and Francis Ltd., 2022-11) AL-Ghamdi, Maryam Abdu; Alsulami, Rawyah Radi; Bakkar, Ashraf; Kumosani, Taha Abullah; Barrbour, Elie Kamil; Abulnaja, Khalid Omar; Huwait, Etimad; Moselhy, Said Salama
Autophagy is a protective mechanism important in human dis- eases as cancer. We evaluated the impact of khalas date extract (KDE) (20-60 mg/mL) on cell viability, morphological changes, DNA fragmentation and gene expression of LC3B-II associated with autophagosome on HepG2 cell line. The GC/MS identification of KDE showed its high content of flavonoids including quercetin, myricetin, kaempferol and catechol. KDE reduced cell viability of HepG2 with IC50 (31.52 mg/mL). Cells treated with KDE showed two band of DNA fragments at (30 and 40 mg) indicating that KDE induced DNA damage and apoptosis in HepG2. The analysis RT-PCR data showed a 0.2-fold increase in the expression of LC3- B in the cells treated with KDE versus control. We concluded that, KDE flavonoids such as quercetin, myricetin kaempferol exhibited anticancer properties manifested by inhibition of HepG2 cell via- bility and induction of apoptosis and upregulation of the pro- autophagy LC3-B gene. ARTICLE HISTORY
Knockdown of WEE1 Gene Induces Cytotoxic Effects in Hairy Cell Leukemia
(Elsevier, 2021-09) El-Khazragy, Nashwa; Bakkar, Ashraf; Elnakib, Mostafa
Clinical Lymphoma Myeloma and Leukemia Volume 21, Supplement 1, September 2021, Page S325 Acute Myeloid Leukemia CLL-393: Knockdown of WEE1 Gene Induces Cytotoxic Effects in Hairy Cell Leukemia Author links open overlay panelNashwaEl-Khazragy12AshrafBakkar3MostafaElnakib4 1 Department of Clinical Pathology-Hematology and Ain Shams Medical Research Institute (MASRI), Faculty of Medicine, Ain Shams University, Cairo, Egypt 2 Global Research Labs, Cairo, Egypt 3 Faculty of Biotechnology, October University for Modern Sciences and Arts, Giza, Egypt 4 Egypt Center for Research and Regenerative Medicine (ECRRM), Cairo, Egypt Available online 30 August 2021. https://doi.org/10.1016/S2152-2650(21)01763-8 Get rights and content Background: Hairy cell leukemia (HCL) is a rare B-cell lymphoid neoplasm with morphological variations that can be difficult to distinguish. A BRAFV600E mutation is found in 80% of patients. Despite the fact that purine analogs (PNA) with or without anti-CD20 antibodies remain the first-line treatment, resistance is still a major issue that has a severe impact on patient outcomes. The successful therapeutic application of short interfering RNA (siRNA) in tumor suppression is being paved by gene silencing. In the cell cycle, the WEE1 gene is the master inhibitor of cyclin-dependent kinase 1. Cumulative data suggests that the WEE1 gene plays a definite function in cell biological processes and that silencing the WEE1 gene could have a variety of implications in cancer cells. Objectives: The purpose of this study was to examine how ex vivo knockdown of the WEE1 gene affects the viability of hairy cell leukemia (HCL) cells in order to see if it has therapeutic potential. Methods: The HCL cell line [Mo T] was used in an experimental in vi’ro investigation. To silence the WEE1 gene ex vivo, cells were transfected using siRNA. Furthermore, the effect of gene knockdown on cell viability was assessed using the MTT test, as well as cell cycle and apoptosis assays performed by flow cytometry. Furthermore, the WEE1 gene expression level in silenced cells was measured and correlated with cellular protein expression. Results: Silencing the WEE1 gene resulted in a significant decrease in cell viability, increased cell apoptosis, and arrested the cell cycle transition from the G1 to the S phase of the cell cycle. In addition, transfected cells showed a significant reduction in WEE1 gene expression, demonstrating the efficiency of gene silencing. Conclusion: In primary hairy cells, silencing the WEE1 gene resulted in significant cytotoxic effects, suggesting that knockdown of the WEE1 gene could be a promising therapeutic target in HCL.
A Meta-Analysis of the Relationship between FGFR3 and TP53 Mutations in Bladder Cancer
(Public Library of Science, 2012) Neuzillet, Yann; Paoletti, Xavier; Ouerhani, Slah; Mongiat-Artus, Pierre; Soliman, Hany; de The, Hugues; Sibony, Mathilde; Denoux, Yves; Molinie, Vincent; Herault, Aurelie; Lepage, May-Linda; Maille, Pascale; Renou, Audrey; Vordos, Dimitri; Abbou, Claude-Clement; Bakkar, Ashraf; Asselain, Bernard; Kourda, Nadia; El Gaaied, Amel; Leroy, Karen; Laplanche, Agnes; Benhamou, Simone; Lebret, Thierry; Allory, Yves; Radvanyi, François
TP53 and FGFR3 mutations are the most common mutations in bladder cancers. FGFR3 mutations are most frequent in low-grade low-stage tumours, whereas TP53 mutations are most frequent in high-grade high-stage tumours. Several studies have reported FGFR3 and TP53 mutations to be mutually exclusive events, whereas others have reported them to be independent. We carried out a meta-analysis of published findings for FGFR3 and TP53 mutations in bladder cancer (535 tumours, 6 publications) and additional unpublished data for 382 tumours. TP53 and FGFR3 mutations were not independent events for all tumours considered together (OR = 0.25 [0.18–0.37], p = 0.0001) or for pT1 tumours alone (OR = 0.47 [0.28–0.79], p = 0.0009). However, if the analysis was restricted to pTa tumours or to muscle-invasive tumours alone, FGFR3 and TP53 mutations were independent events (OR = 0.56 [0.23–1.36] (p = 0.12) and OR = 0.99 [0.37–2.7] (p = 0.35), respectively). After stratification of the tumours by stage and grade, no dependence was detected in the five tumour groups considered (pTaG1 and pTaG2 together, pTaG3, pT1G2, pT1G3, pT2-4). These differences in findings can be attributed to the putative existence of two different pathways of tumour progression in bladder cancer: the CIS pathway, in which FGFR3 mutations are rare, and the Ta pathway, in which FGFR3 mutations are frequent. TP53 mutations occur at the earliest stage of the CIS pathway, whereas they occur would much later in the Ta pathway, at the T1G3 or muscle-invasive stage.
Pergularia tomentosa coupled with selenium nanoparticles salvaged lead acetate-induced redox imbalance, inflammation, apoptosis, and disruption of neurotransmission in rats’ brain
(Walter de Gruyter GmbH, 2022-11) Othman, Mohamed S; Obeidat, Sofian T; Aleid, Ghada M; Abdel-Daim, Mohamed M; Habotta, Ola A; Schwartz, Laurent; Al-Bagawi, Amal H; Hussein, Manal M; Bakkar, Ashraf
In this study, the nepuroprotective potential of either Pergularia tomentosa leaf methanolic extract (PtE) alone or in combination with selenium nanoparticles (SeNPs-PtE) was investigated against lead acetate (PbAc)- induced neurotoxicity. Experimental rats were pretreated with PtE (100 mg/kg) or SeNPs-PtE (0.5 mg/kg) and injected intraperitoneally with PbAc (20 mg/kg) for 2 weeks. Notably, SeNPs-PtE decreased brain Pb accumulation and enhanced the level of dopamine and the activity of AChE compared to the control rats. In addition, elevated neural levels of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione along with decreased lipid peroxidation levels were noticed in pretreated groups with SeNPs-PtE. Moreover, SeNPs-PtE significantly sup- pressed neural inflammation, as indicated by lower levels of interleukin-1 beta, interleukin-6, tumor necrosis factor- alpha, nuclear factor-kappa B p65, and nitric oxide in the examined brain tissue. The molecular results also unveiled significant down-regulation in iNOS gene expression in the brains of SeNPs-PtE-treated rats. In addition, SeNPs- PtE administration counteracted the neural loss by increasing B-cell lymphoma 2 (Bcl-2) and brain-derived neurotrophic factor levels as well as decreasing BCL2-associated X protein and caspase-3 levels. To sum up, our data suggest that P. tomentosa extract alone or in combination with SeNPs has great potential in reversing the neural tissue impairment induced by PbAc via its antioxidant, anti-inflammatory, and anti-apoptotic activities. This study might have therapeutic implications in preventing and treating several lead-induced neurological disorders.
PREPARATION OF A MORE STABLE LYOPHILIZED BCG-T WITH THE SAME BIOPOTENTIAL FOR BLADDER CANCER IMMUNOTHERAPY
(Inventi, 4/15/2017) Mohamed, Aly Fahmy; Bakkar, Ashraf; Yahia, Mohamed; Yasser, Menatallah
BCG-T is a new trend for immunotherapy of bladder cancer as an alternative to chemotherapy. The available product is liquid form of a limited stability profile. The present study aims to prepare a lyophilized form of BCG-T using different stabilizer namely Na glutamate and lactose. Stability of pharmaceutical lyophilized injection dosage form compared with the liquid form was assessed revealing that the Na glutamate and lactose stabilized BCG-T was significantly more stable than BCG-T in the liquid formula. Also, the dry weight and relative humidity and safety of both Na glutamate and lactose stabilized BCG-T were insignificantly different from the liquid form (P >0.05).
PTEN rs701848 Polymorphism is Associated with Trastuzumab Resistance in HER2-positive Metastatic Breast Cancer and Predicts Progression-free Survival
(Elsevier, 2023-01) El-Khazragy, Nashwa; Gaballah, Ahmed; Bakkar, Ashraf; Hemida, Eman H.A; Samir, Nehal; Tarek, Marwa; Adly, Heba M; Saleh, Saleh A.K; Hanna, Demiana H
The high mortality rate of HER-2+ve breast cancer (BC) is linked to Trastuzumab resistance, which is linked to PTEN rs701848 variants. In 160 patients with metastatic HER2+ve BC who were treated with trastuzumab, the PTEN genotypes were determined. Obtained results revealed that the PTEN locus is a major predictor of Trastuzumab resistance, and the C allele is linked to a higher risk. Background: Trastuzumab is an effective therapeutic approach for HER2-positive metastatic breast cancer (BC). However, a considerable number of patients develop resistance along the course of the disease. PTEN rs701848 polymorphisms are associated with an increased risk of developing cancer and have a potential role in predict- ing drug resistance. Objective: We studied the significance of PTEN rs701848 variants as significant predictors for trastuzumab resistance in HER2-positive metastatic BC patients. Therefore, considering their value in predicting clinical outcomes. Materials and Methods: This case-control study was conducted among female patients with HER2-positive metastatic breast cancer who underwent Trastuzumab therapy during the period from March 2017 to December 2020. PTEN rs701848 genotypes were analyzed in 160 HER2-positive metastatic breast cancer who received Trastuzumab therapy and clinically monitored for therapeutic response. Results: PTEN rs701848 is deemed a significant predictor of Trastuzumab resistance and an independent prognostic factor of progression-free survival (PPFS). In particular, the C allele is associated with increased risk for Trastuzumab resistance and shorter PFS as compared to the homozygous TT genotype. Conclusion: PTEN rs701848 is significant predictor of trastuzumab resistance. Therefore, their value in predicting clinical outcomes is recommended Clinical Breast Cancer, Vol. 000, No.xxx, 1–9 © 2022 Elsevier Inc. All rights reserved.
Strigol1/albumin/chitosan nanoparticles decrease cell viability, induce apoptosis and alter metabolomics profile in HepG2 cancer cell line
(Elsevier Masson s.r.l., 2024-06) Al-Malki, Abdulrahman L; Bakkar, Ashraf; Huwait, Etimad A; Barbour, Elie K; Abulnaja, Kalid O; Kumosani, Taha A; Moselhy, Said S
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. The journal was alerted about issues with images within Figure 3a, which appear to have multiple duplications, as detailed here: PubPeer - Strigol1/albumin/chitosan nanoparticles decrease cell viabil…. The journal requested the authors to provide an explanation to these concerns and the associated raw data, but this request was not satisfactorily fulfilled. The Editor-in-Chief assessed the case and decided to retract the article.
Strigol1/albumin/chitosan nanoparticles decrease cell viability, induce apoptosis and alter metabolomics profile in HepG2 cancer cell line
(Elsevier, 08/02/2021) Al-Malki, Abdulrahman L; Bakkar, Ashraf; Huwait, Etimad; Barbour, Elie K; Abulnaja, Kalid O; Kumosani, Taha A; Moselhy, Said S
Biomedicine & Pharmacotherapy Volume 142, October 2021, 111960 Strigol1/albumin/chitosan nanoparticles decrease cell viability, induce apoptosis and alter metabolomics profile in HepG2 cancer cell line Author links open overlay panelAbdulrahman L.Al-MalkiabcAshrafBakkardEtimad A.HuwaitaElie K.BarbourabeKalid O.AbulnajaabcTaha A.KumosaniabfSaid S.Moselhyg a Biochemistry Department, Faculty of Science, King Abdulaziz University (KAU), Jeddah, Saudi Arabia b Experimental Biochemistry Unit, King Fahd Medical Research Centre, King Abdulaziz University, Saudi Arabia c Bioactive Natural Products Research Group, King Abdulaziz University. Jeddah, Saudi Arabia d Modern Sciences and Arts University (MSA), 6th October, Giza, Egypt e Director of R and D Department, Opticon Hygiene Consulting, Oechsli 7, 8807 Freienbach, Switzerland f Production of Bio-products for Industrial Applications Research Group, King Abdulaziz University g Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt Received 16 March 2021, Revised 21 July 2021, Accepted 22 July 2021, Available online 2 August 2021. crossmark-logo https://doi.org/10.1016/j.biopha.2021.111960 Get rights and content Under a Creative Commons licenseopen access Highlights • Novel strigol nanoparticles (S/A/CNP) exhibit antiproliferative activity against HepG2 cells through dose dependent. • The S/A/CNP significantly reduces Krebs cycle intermediate and decrease glutamine level as energy source substrate. • The S/A/CNP induce morphological changes and trigger pro-apoptotic effects in HepG2. • The S/A/CNP reduces spermine and spermidine and inhibit DNA replication. Abstract Hepatocellular carcinoma is one of the most common causes of cancer-related deaths globally. Bioavailable, effective and safe therapeutic agents are urgently needed for cancer treatment. This study evaluated the metabolomics profiling, anti-proliferative and pro-apoptotic effects of strigol/albumin/chitosan nanoparticles (S/A/CNP) on HepG2 cell line. The diameter of S/A/CNP was (5 ± 0.01) nm. The IC50 was 180.4 nM and 47.6 nM for Strigol1 and S/A/CNP, respectively, after incubation for 24 h with HepG2 cells. By increasing the concentration of S/A/CNP, there was chromatin condensation, degranulation in the cytoplasm and shrinking in cell size indicating pro-apoptotic activity. Metabolomics profiling of the exposed cells by LC/MS/MS revealed that S/A/CNP up-regulated epigenetic intermediates (spermine and spermidine) and down-regulated energy production pathway and significantly decreased glutamine (P < 0.001). These findings demonstrated that S/A/CNP has anti-proliferative, apoptotic effects and modulate energetic, and epigenetic metabolites in the hepatocellular carcinoma cell line (HepG2).
Targeting Hyaluronidase for Cancer Therapy: Antitumor Activity of Sulfated Hyaluronic Acid in Prostate Cancer Cells
(American Association for Cancer Research, 2011-06) Lokeshwar, Vinata B; Bakkar, Ashraf; Cerwinka, Wolfgang H; Lopez, Luis E.; Cerwinka, Wolfgang H.; Lokeshwar, Vinata B.
The tumor cell–derived hyaluronidase (HAase) HYAL-1 degrades hyaluronic acid (HA) into proangiogenic fragments that support tumor progression. Although HYAL-1 is a critical determinant of tumor progression and a marker for cancer diagnosis and metastasis prediction, it has not been evaluated as a target for cancer therapy. Similarly, sulfated hyaluronic acid (sHA) has not been evaluated for biological activity, although it is an HAase inhibitor. In this study, we show that sHA is a potent inhibitor of prostate cancer. sHA blocked the proliferation, motility, and invasion of LNCaP, LNCaP-AI, DU145, and LAPC-4 prostate cancer cells, and induced caspase-8–dependent apoptosis associated with downregulation of Bcl-2 and phospho-Bad. sHA inhibited Akt signaling including androgen receptor (AR) phosphorylation, AR activity, nuclear factor κB (NFκB) activation, and VEGF expression. These effects were traced to a blockade in complex formation between phosphoinositide 3-kinase (PI3K) and HA receptors and to a transcriptional downregulation of HA receptors, CD44, and RHAMM, along with PI3K inhibition. Angiogenic HA fragments or overexpression of myristoylated Akt or HA receptors blunted these effects of sHA, implicating a feedback loop between HA receptors and PI3K/Akt signaling in the mechanism of action. In an animal model, sHA strongly inhibited LNCaP-AI prostate tumor growth without causing weight loss or apparent serum-organ toxicity. Inhibition of tumor growth was accompanied by a significant decrease in tumor angiogenesis and an increase in apoptosis index. Taken together, our findings offer mechanistic insights into the tumor-associated HA–HAase system and a preclinical proof-of-concept of the safety and efficacy of sHA to control prostate cancer growth and progression
Upregulation of leukemia-induced non-coding activator RNA (LUNAR1) 3 Predicts Poor Outcome in Pediatric T-acute Lymphoblastic Leukemia
(Elsevier, 10/26/2021) EL-Khazragy, Nashwa; Abdel Aziz, Mahfouz A; Hesham, Manar; Matbouly, Safa; Abdallah Mostafa, Sally; Bakkar, Ashraf; Abouelnile, Mariam; Noufal, Yassmin; Mahran, Nievin Ahmed; Abdlkhalek, Marwa Ali; Abdelmaksoud, Mariam Fathy
T-cell Acute Lymphoblastic Leukemia (T-ALL) accounts for around 10-15% of all lymphoblastic leukemia in children. Previous studies have proven that dysregulation of Leukemia-induced non-coding activator RNA-1 (LUNAR1) expression promotes T-ALL cell growth by enhancing the NOTCH1/IGF-1R signaling pathway. We aimed to investigate the prognostic value of LUNAR1 in pediatric T-ALL, in addition, to find out its association with NOTCH1 and IGF-1R. The LUNAR1, NOTCH1, and IGF-IR gene expression were measured in peripheral blood (PB) samples of l85 children with T-ALL and forty non-leukemic samples as a control group. Cox regression analysis revealed that overexpression of LUNAR1, NOTCH1, and IGF-IR was significantly correlated with poor prognosis, short overall survival, and progression-free survival. We concluded that LUNAR1 could serve as an independent prognostic biomarker for T-ALL in children.
ZINC OXIDE NANORODS INDUCED APOPTOSIS IN HUMAN PROSTATIC AND HEPATOCELLULAR CARCINOMA VIA MITOCHONDRIA DYSFUNCTION MEDIATED THOUGH BAX/ BCL-2 WITH P53 ACTIVATION
(Inventi, 2017-06) Sabatier, Jean–Marc; Bakkar, Ashraf; Shebl, Rania I; Mohamed, Aly Fahmy; Hassan, Amr; Gamal, Omar
The present study aimed to experimentally synthesis zinc oxide nanorods (ZnO NRs) using albumin as bio-template by a sol-gel method and to characterize the products using UV-Visible, FTIR, XRD, TGA and HRTEM. The crystallinity and morphology of the ZnO NRs were confirmed to have an average diameter of 70 nm and 250 nm length. The formation mechanism depends on the nucleation of Zn+2 in sites of the albumin followed by Zn+2 assembly in the cavity of albumin and finally thermal treatment to form ZnO in rod shape then calcination to final form ZnO NRs form as shown in HRTEM. Cytotoxicity of developed ZnO-NRs was conducted using MTT assay on both HepG2 and PC-3 cells. Data revealed that ZnO-NPs were toxic to both HepG2 and PC-3 cell lines displayed a concentration dependent viability. The flow cytometry illustrated that apoptosis of hepatocellular carcinoma (HepG2) depends on the cell growth arrest at G1/S phase indicated that inhibition Cyclin E (CDK 2) while prostatic carcinoma (PC-3) depends cell growth arrest at G2/M phase indicated that inhibition of Cyclin ACDK1. The apoptotic mechanism was investigated using rt-PCR. The apoptotic mechanism in both cell lines HepG2 and PC-3 was depended on the upregulated of Bax protein and down regulation of Bcl-2 indicated that the mechanism of mitochondrial outer membrane permeability (MOMP) or mitochondria dysfunction was dependent on activation of P53 protein.