Cytotoxic Effect of Phoenix dactylifera (Iraqi Date) Leaves and Fruits Extracts against Breast Cancers Cell Lines.

OBJECTIVE: Now a day's cancerous diseases are the most prevalent life threatening that spreading because of the lifestyle. Its due to uncontrolled growth of cell which can be cured if diagnosed in early stage. Treatment of cancer depends on the various internal and external factors causing cancer. The main objective of this study is using herbal based medicine to manage breast cancer, the second most common type of cancer in the world. METHODS: In this study, the anticancer effect of two Iraqi date palm part extracts (leaves and fruits) against panel of breast cancer cell lines (AMJ13و MCF7, MDA-MB-231, CAL51) in vitro to evaluate their possible antitumor effect and their safety on normal cell line (MEF). RESULTS: The Phoenix dactylifera (dray Zahdi) fresh leave extract showed highly cytotoxic effects in all breast cancer cell lines. The leaves extract was showed concentration dependent cytotoxicity effects after 72 h exposure time. Leave extracts was effective against AMJ13 cell line. The effective concentrations in both cancer cells ranged from 2500-20000 µg/ ml with inhibition percentage against AMJ13 was (66.7, 70.6, 53, and 54%). While the effect against MCF7, MDA-MB, and CAL51 cell lines were less with significant effect only at two concentrations (10000- 20000 µg/ ml) causing 64.3, and 64.3% growth inhibition respectively in MCF7, and 40, and 50% respectively in MDA-MB, and 44.0, and 52.0% respectively in CAL51. The dray date fruit extract has no significant cytotoxicity against all the cancer cells. Both extracts have no effect against normal fibroblast cells. CONCLUSION: In conclusion, Phoenix dactylifera fresh leave extract shows promising anticancer properties while the fruit extract has no direct anticancer effect.

The Effect of NF-κB Deactivation on Cancer Cell Response to ALA Mediated Photodynamic Therapy.

OBJECTIVE: Breast cancer is one of the most widespread tumors among women worldwide, which is difficult to treat due to the presence of chemoresistance and the risk of tumor recurrence and metastasis. There is a pressing necessity to develop efficient treatments to improve response for treatment and increase prolong survival of breast cancer patients. Photodynamic therapy (PDT) has attracted interest for its features as a noninvasive and relatively selective cancer treatment. This method relies on light-activated photosensitizers that, upon absorbing light, generate reactive oxygen species (ROS) with powerful cell-killing outcomes. Nuclear factor kappa B (NF-κB), a transcription factor, plays a key role in cancer development by regulating cell proliferation, differentiation, and survival. Inhibiting NF-κB can sensitize tumor cells to chemotherapeutic agents. Dimethyl fumarate (DMF), an NF-κB inhibitor approved by the FDA for multiple sclerosis treatment, has further shown promise in suppressing breast cancer cell growth in vitro. We hypothesized that combining PDT with Dimethyl fumarate (DMF) could further enhance therapeutic efficacy for both treatment modalities. METHODS: In the current study, we explored the PDT effect of 1 and 2 mM aminolaevulinic acid (ALA) and low-power He-Ne laser irradiation combined with different concentrations of DMF (2.5, 1.25, or 0.652 µg/ml) against hormone nonresponsive AMJ13 breast cancer cell line that is derived from Iraqi patient. RESULTS: Our results demonstrated that co-administration with all tested DMF concentrations significantly enhanced the cytotoxicity of PDT antitumor effect. The combination index analysis showed presence of synergism in combining PDT with DMF. CONCLUSION: This finding suggests that the combination of PDT with DMF could be a promising novel strategy against triple negative breast cancer that could be applied clinically due to the fact that both of these treatments are already clinically approved therapies.

Increased Expression of the ABCA1 and ABCA3 Transporter Genes is Associated with Cisplatin Resistance in Breast Cancer Cells.

OBJECTIVE: Breast cancer (BC) is a highly malignant neoplasm with resistance to therapeutics that are related to genes associated with multidrug resistance. The excessive expression of ATP-binding cassette transporters (ABCs) genes, including ABCA1 and ABCA3, is a primary factor contributing to the increased effluent of cell-toxic drugs and subsequent treatment resistance. Therefore, the current work aimed to explore the role of ABCA1 and ABCA3 in chemoresistance activity against cisplatin in breast cancer cells. METHODS: The current study compared the AMJ13 breast cancer cells derived from a woman Iraqi patient, which are hormone receptor-negative, with MCF-7 breast cancer cells, which are hormone receptor-positive.  Cytotoxic assay (CCK-8 assay) is used to measure the cell's viability and cytotoxic activity after it has been treated with cisplatin. Morphological Study using crystal violet stain to examine cytological changes was conducted. Quantitative RT-PCR is used to measure how much the ABCA1, and 3 genes mRNA are being expressed before and after treatment. RESULTS: The CCK-8 assay found that IC50 values of cisplatin in AMJ13 and MCF-7 cells were 202.2 µg/ml and 90.23 µg/ml, respectively. The IC50 value of AMJ13 is 2-fold higher than in MCF-7 cells. The QPCR study revealed that breast cancer cell lines AMJ13 and MCF-7 subjected to cisplatin showed upregulated levels of ABCA1 and ABCA3 expression. Experiments with cytotoxicity assays demonstrate that higher expression of ABCA1 and ABCA3 in AMJ13 and MCF-7 breast cancer cell lines is linked to their resistance.  Conclusion: The findings of this study suggest that the ABCA1 and ABCA3 transporters play a significant role in the resistance to cisplatin and,.

Combined oncolytic virotherapy gold nanoparticles as synergistic immunotherapy agent in breast cancer control.

Combining viruses and nanoparticles may be a way to successfully treat cancer and minimize adverse effects. The current work aimed to evaluate the efficacy of a specific combination of gold nanoparticles (GNPs) and Newcastle disease virus (NDV) to enhance the antitumor effect of breast cancer in both in vitro and in vivo models. Two human breast cancer cell lines (MCF-7 and AMJ-13) and a normal epithelial cell line (HBL-100) were used and treated with NDV and/or GNPs. The MTT assay was used to study the anticancer potentials of NDV and GNP. The colony formation assay and apoptosis markers were used to confirm the killing mechanisms of NDV and GNP against breast cancer cell lines. p53 and caspase-9 expression tested by the qRT-PCR technique. Our results showed that combination therapy had a significant killing effect against breast cancer cells. The findings demonstrated that NDV and GNPs induced apoptosis in cancer cells by activating caspase-9, the p53 protein, and other proteins related to apoptosis, which holds promise as a combination therapy for breast cancer.

Papaverine Enhances the Oncolytic Effects of Newcastle Disease Virus on Breast Cancer In Vitro and In Vivo.

Breast cancer is a lethal disease in females worldwide and needs effective treatment. Targeting cancer cells with selective and safe treatment seems like the best choice, as most chemotherapeutic drugs act unselectively. Papaverine showed promising antitumor activity with a high safety profile and increased blood flow through vasodilation. At the same time, it was widely noticed that virotherapy using the Newcastle disease virus proved to be safe and selective against a broad range of cancer cells. Furthermore, combination therapy is favorable, as it attacks cancer cells with multiple mechanisms and enhances virus entrance into the tumor mass, overcoming cancer cells' resistance to therapy. Therefore, we aimed at assessing the novel combination of the AMHA1 strain of Newcastle disease virus (NDV) and nonnarcotic opium alkaloid (papaverine) against breast cancer models in vitro and in vivo. Methods. In vitro experiments used two human breast cancer cell lines and one normal cell line and were treated with NDV, papaverine, and a combination. The study included a cell viability MTT assay, morphological analysis, and apoptosis detection. Animal experiments used the AN3 mouse mammary adenocarcinoma tumor model. Evaluation of the antitumor activity included growth inhibition measurement; the immunohistochemistry assay measured caspase protein expression. Finally, a semiquantitative microarray assay was used to screen changes in apoptotic proteins. In vitro, results showed that the combination therapy induces synergistic cytotoxicity and apoptosis against cancer cells with a negligible cytotoxic effect on normal cells. In vivo, combination treatment induced a significant antitumor effect with an obvious regression in tumor size and a remarkable and significant expression of caspase-3, caspase-8, and caspase-9 compared to monotherapies. Microarray analysis shows higher apoptosis protein levels in the combination therapy group. In conclusion, this study demonstrated the role of papaverine in enhancing the antitumor activity of NDV, suggesting a promising strategy for breast cancer therapy through nonchemotherapeutic drugs.

Anticancer activity of retinoic acid against breast cancer cells derived from an Iraqi patient.

Objective: Breast cancer is one of the most lethal diseases in women, both worldwide and in Iraq. The high mortality rate is attributed primarily to the chemoresistance to conventional therapeutics. The search for effective and safe treatments is critical. One promising agent that has shown activity against various cancer types is retinoic acid (RA). Methods: RA was tested against a panel of international breast cancer cell lines and compared with Iraqi patient-derived hormone-independent breast cancer cells through MTT viability assays. Cytopathology was assessed under an inverted microscope, and apoptotic induction was evaluated with acridine orange propidium iodide assays. Results: AMJ13 breast cancer cells were more sensitive to killing induced by RA than MCF-7 and CAL-51 cells. By contrast, normal HBL-100 cells showed a negligible effect. Cytological changes were observed in all cancer cells treated with RA, whereas no changes were observed in normal HBL-100 cells. Iraqi patient-derived breast cancer cells showed a higher percentage of cells undergoing apoptosis after RA treatment than the other breast cancer cells. Conclusion: We suggest RA as a possible breast cancer treatment with potential for clinical application with high safety.

Oncolytic Newcastle Disease Virus Co-Delivered with Modified PLGA Nanoparticles Encapsulating Temozolomide against Glioblastoma Cells: Developing an Effective Treatment Strategy.

Glioblastoma multiforme (GBM) is considered to be one of the most serious version of primary malignant tumors. Temozolomide (TMZ), an anti-cancer drug, is the most common chemotherapeutic agent used for patients suffering from GBM. However, due to its inherent instability, short biological half-life, and dose-limiting characteristics, alternatives to TMZ have been sought. In this study, the TMZ-loaded PLGA nanoparticles were prepared by employing the emulsion solvent evaporation technique. The prepared TMZ-PLGA-NPs were characterized using FT-IR, zeta potential analyses, XRD pattern, particle size estimation, TEM, and FE-SEM observations. The virotherapy, being safe, selective, and effective in combating cancer, was employed, and TMZ-PLGA-NPs and oncolytic Newcastle Disease Virus (NDV) were co-administered for the purpose. An AMHA1-attenuated strain of NDV was propagated in chicken embryos, and the virus was titrated in Vero-slammed cells to determine the infective dose. The in vitro cytotoxic effects of the TMZ, NDV, and the TMZ-PLGA-NPs against the human glioblastoma cancer cell line, AMGM5, and the normal cell line of rat embryo fibroblasts (REFs) were evaluated. The synergistic effects of the nano-formulation and viral strain combined therapy was observed on the cell lines in MTT viability assays, together with the Chou-Talalay tests. The outcomes of the in vitro investigation revealed that the drug combinations of NDV and TMZ, as well as NDV and TMZ-PLGA-NPs exerted the synergistic enhancements of the antitumor activity on the AMGM5 cell lines. The effectiveness of both the mono, and combined treatments on the capability of AMGM5 cells to form colonies were also examined with crystal violet dyeing tests. The morphological features, and apoptotic reactions of the treated cells were investigated by utilizing the phase-contrast inverted microscopic examinations, and acridine orange/propidium iodide double-staining tests. Based on the current findings, the potential for the use of TMZ and NDV as part of a combination treatment of GBM is significant, and may work for patients suffering from GBM.

3-Dimensional coculture of breast cancer cell lines with adipose tissue-Derived stem cells reveals the efficiency of oncolytic Newcastle disease virus infection via labeling technology.

Oncolytic virotherapy is one of the emerging biological therapeutics that needs a more efficient in vitro tumor model to overcome the two-dimensional (2D) monolayer tumor cell culture model's inability to maintain tissue-specific structure. This is to offer significant prognostic preclinical assessment findings. One of the best models that can mimic the in vivo model in vitro are the three-dimensional (3D) tumor-normal cell coculture systems, which can be employed in preclinical oncolytic virus therapeutics. Thus, we developed our 3D coculture system in vitro using two types of breast cancer cell lines showing different receptor statuses cocultured with adipose tissue-derived mesenchymal stem cells. The cells were cultured in a floater tissue culture plate to allow spheroids formation, and then the spheroids were collected and transferred to a scaffold spheroids dish. These 3D culture systems were used to evaluate oncolytic Newcastle disease virus AMHA1 strain infectivity and antitumor activity using a tracking system of the Newcastle disease virus (NDV) labeled with fluorescent PKH67 linker to follow the virus entry into target cells. This provides evidence that the NDV AMHA1 strain is an efficient oncolytic agent. The fluorescently detected virus particles showed high intensity in both coculture spheres. Strategies for chemically introducing fluorescent dyes into NDV particles extract quantitative information from the infected cancer models. In conclusion, the results indicate that the NDV AMHA1 strain efficiently replicates and induces an antitumor effect in cancer-normal 3D coculture systems, indicating efficient clinical outcomes.

Glucose Deprivation Induced by Acarbose and Oncolytic Newcastle Disease Virus Promote Metabolic Oxidative Stress and Cell Death in a Breast Cancer Model.

Cancer cells are distinguished by enhanced glucose uptake and an aerobic glycolysis pathway in which its products support metabolic demands for cancer cell growth and proliferation. Inhibition of aerobic glycolysis is a smart therapeutic approach to target the progression of the cancer cell. We employed acarbose (ACA), a particular alpha-glucosidase inhibitor, to induce glucose deprivation combined with oncolytic Newcastle disease virus (NDV) to enhance antitumor activity. In this work, we used a mouse model of breast cancer with mammary adenocarcinoma tumor cells (AN3) that were treated with ACA, NDV, and a combination of both. The study included antitumor efficacy, relative body weight, glucose level, hexokinase (HK-1) level by ELISA, glycolysis product (pyruvate), total ATP, oxidative stress (ROS and reduced glutathione), and apoptosis by immunohistochemistry. The results showed significant antitumor efficacy against breast cancer after treatment with combination therapy. Antitumor efficacy was accompanied by a reduction in body weight and glucose level, HK-1 downregulation, inhibition of glycolysis products (pyruvate), total ATP, induction of oxidative stress (increase ROS and decrease reduced glutathione), and apoptotic cell death. The findings propose a novel anti-breast cancer combination involving the suppression of glycolysis, glucose deprivation, oxidative stress, and apoptosis, which can be translated clinically.

Bio-hybrid dental implants prepared using stem cells with ß-TCP-coated titanium and zirconia.

PURPOSE: This study investigated periodontal ligament (PDL) restoration in osseointegrated implants using stem cells. METHODS: Commercial pure titanium and zirconium oxide (zirconia) were coated with beta-tricalcium phosphate (ß-TCP) using a long-pulse Nd:YAG laser (1,064 nm). Isolated bone marrow mesenchymal cells (BMMSCs) from rabbit tibia and femur, isolated PDL stem cells (PDLSCs) from the lower right incisor, and co-cultured BMMSCs and PDLSCs were tested for periostin markers using an immunofluorescent assay. Implants with 3D-engineered tissue were implanted into the lower right central incisors after extraction from rabbits. Forty implants (Ti or zirconia) were subdivided according to the duration of implantation (healing period: 45 or 90 days). Each subgroup (20 implants) was subdivided into 4 groups (without cells, PDLSC sheets, BMMSC sheets, and co-culture cell sheets). All groups underwent histological testing involving haematoxylin and eosin staining and immunohistochemistry, stereoscopic analysis to measure the PDL width, and field emission scanning electron microscopy (FESEM). The natural lower central incisors were used as controls. RESULTS: The BMMSCs co-cultured with PDLSCs generated a well-formed PDL tissue that exhibited positive periostin expression. Histological analysis showed that the implantation of coated (Ti and zirconia) dental implants without a cell sheet resulted in a well-osseointegrated implant at both healing intervals, which was confirmed with FESEM analysis and negative periostin expression. The mesenchymal tissue structured from PDLSCs only or co-cultured (BMMSCs and PDLSCs) could form a natural periodontal tissue with no significant difference between Ti and zirconia implants, consequently forming a biohybrid dental implant. Green fluorescence for periostin was clearly detected around the biohybrid implants after 45 and 90 days. FESEM showed the invasion of PDL-like fibres perpendicular to the cementum of the bio-hybrid implants. CONCLUSIONS: ß-TCP-coated (Ti and zirconia) implants generated periodontal tissue and formed biohybrid implants when mesenchymal-tissue-layered cell sheets were isolated from PDLSCs alone or co-cultured BMMSCs and PDLSCs.

Glucose deprivation using 2-deoxyglucose and acarbose induce metabolic oxidative stress and apoptosis in female mice bearing breast cancer.

A characteristic of cancer cells is increased glucose uptake and glycolysis for energy production and hydroperoxide detoxification due to mitochondrial dysfunction. Thus, inhibition of glucose uptake and glycolysis represent smart novel therapy. We used 2-deoxyglucose (2DG) as a glycolysis inhibitor and acarbose (ACA), a specific alpha-glucosidase inhibitor, to decrease glucose uptake. Mice bearing mammary adenocarcinoma tumors were treated by 2DG and/or ACA. Relative tumor volume, tumor growth inhibition rate, relative body weight, glucose concentration, hexokinase-1 protein level by ELISA, pyruvate, and ATP (glycolysis products), reactive oxygen species (ROS), total glutathione T-GSH, apoptosis, and histopathology were measured in treated and untreated groups. Our results showed that combination therapy inhibited tumor volume and increased tumor growth inhibition rate, body weight reduction, decreasing glucose level, HK-1 level, and inhibition of glycolysis products. In addition, combination therapy induced oxidative stress, increase ROS, and decrease T-GSH. Furthermore, immunohistochemistry examination showed the broader area of apoptosis in breast cancer treated by combination agents. In conclusion, our result revealed that the novel combination inhibits glycolysis and glucose uptake and induced oxidative stress and apoptosis.

Direct Reprogramming of Mice Skin Fibroblasts into Insulin-Producing Cells In Vitro.

Transdifferentiation means mature cell conversion into other mature cells. Ethical issues, epigenetic failure, or teratoma development are found in cellular reprogramming strategies. Thus, new methods are needed. This study aimed to develop a new novel formula of chemical molecules and growth factors that differentiate skin fibroblasts into insulin-producing cells (IPCs). Newborn mice fibroblasts differentiated using four induction methods into IPCs to search for the best method. Fibroblasts, stem cells, and pancreatic markers were identified using an immunocytochemistry (ICC) assay. Insulin was measured using ELISA and dithizone (DTZ) assays. The skin fibroblasts were induced successfully into IPCs. The best method to obtain IPCs was indicated by measuring insulin concentration in differentiated cell supernatant from all induced cells by the four methods. The protein expression of the pancreatic markers of induced cells increased with time, as indicated by the ICC assay. OCT3/4 increased on day 9, after which the expression tended to decrease. DTZ-positive clusters were observed on day 16. Secreted insulin of differentiated cells was injected in streptozotocin-induced diabetic mice, which decreased blood glucose levels after injection. This study indicated an efficient new chemical method for transdifferentiating skin fibroblasts into functional IPCs, which is a promising method for diabetes mellitus therapy.

Isolation of Bovine leukemia virus from cows with persistent lymphocytosis in Iraq.

This is the first study to report on the isolation of bovine leukemia virus (BLV) from peripheral blood mononuclear cells of two cross bred cows in Iraq. The cattle were seropositive by ELISA when selected while being surveyed for the detection of BLV. Among six cows, two were cases of persistent lymphocytosis (PL). Cytopathology was characterized by the formation of multinucleated giant cells (syncytia) and cytoplasmic vacuoles. Moreover, the viruses produced clear plaques on the monolayer of the primary fetal calf kidney (FCK) cells. Inhibition of plaque formation by BLV-antisera suggested a diagnosis of BLV, which was further confirmed by PCR. Cells infected with the isolates were positive to a monoclonal antibody against the viral gp51 trans-membrane glycoprotein by immunocytochemistry. Both isolates replicated and induced cytopathic effects in bovine and human cell line cultures. Phylogenetic analysis based on partial gp51 env gene sequences revealed that Iraqi strain highly homogenous with Turkey strain (100%) and had 1% distance value with other world strains. In conclusion, this present study found that BLV-infected cattle with PL can be a source for viral isolation, and the cytopathological features of the virus infection are arranged and differ depending on the cell type. This is the first study to report on the isolation of the EBL virus in Iraq, and it provides the basis for further studies about a BLV Iraqi strain that can help control this disease.

Linalool-Loaded Glutathione-Modified Gold Nanoparticles Conjugated with CALNN Peptide as Apoptosis Inducer and NF-κB Translocation Inhibitor in SKOV-3 Cell Line.

BACKGROUND: Linalool is a monoterpene compound with various potential therapeutic applications in several medical fields. Previous studies have indicated the activity of linalool against cell lines; however, its high level of toxicity restricts its use. The aim of this study was to design and manufacture compounds with a novel structure that can be used for loading linalool, to reduce its toxicity and improve its reachable ability. METHODS: We synthesized and characterized a new molecule for loading linalool onto gold nanoparticles (GNPs) capped with glutathione and conjugated with a CALNN peptide. Linalool was loaded onto the GNPs via the reaction of the surface groups of both linalool and the GNPs. Moreover, the target peptide could be loaded onto the surface of the GNPs via a chemical reaction. The cytotoxic effects of linalool-GNP (LG) and linalool-GNP-CALNN peptide (LGC) conjugates against ovarian cancer cells were investigated, as were the possible mechanisms underlying the induction of apoptosis. RESULTS: Our findings illustrated the significant antiproliferative effect of LG and LGC on SKOV-3 cells. The cytotoxicity assay demonstrated that LG and LGC were selectively toxic in cancer cells and induced apoptosis by activating caspase-8, the p53 protein, and various proteins involved in apoptosis. The present data demonstrated that LG and LGC have a high therapeutic potential and should be given particular consideration as anticancer drug-delivery systems, as LG and LGC were remarkably more cytotoxic against a cancer cell line than were linalool and GNPs alone. CONCLUSION: We concluded that LG and LGC are promising compounds that can be used for treating ovarian cancer (SKOV-3) cells via the induction of apoptosis through extrinsic and intrinsic pathways.

Hexokinase inhibition using D-Mannoheptulose enhances oncolytic newcastle disease virus-mediated killing of breast cancer cells.

BACKGROUND: Most cancer cells exhibit increased glycolysis and use this metabolic pathway cell growth and proliferation. Targeting cancer cells' metabolism is a promising strategy in inhibiting cancer cell progression. We used D-Mannoheptulose, a specific hexokinase inhibitor, to inhibit glycolysis to enhance the Newcastle disease virus anti-tumor effect. METHODS: Human breast cancer cells were treated by NDV and/or hexokinase inhibitor. The study included cell viability, apoptosis, and study levels of hexokinase enzyme, pyruvate, ATP, and acidity. The combination index was measured to determine the synergism of NDV and hexokinase inhibitor. RESULTS: The results showed synergistic cytotoxicity against breast cancer cells by combination therapy but no cytotoxic effect against normal cells. The effect was accompanied by apoptotic cell death and hexokinase downregulation and inhibition to glycolysis products, pyruvate, ATP, and acidity. CONCLUSIONS: The combination treatment showed safe significant tumor cell proliferation inhibition compared to monotherapies suggesting a novel strategy for anti-breast cancer therapy through glycolysis inhibition by hexokinase downregulation.

Newcastle disease virus suppress glycolysis pathway and induce breast cancer cells death.

Newcastle disease virus (NDV) can modulate cancer cell signaling pathway and induce apoptosis in cancer cells. Cancer cells increase their glycolysis rates to meet the energy demands for their survival and generate ATP as the primary energy source for cell growth and proliferation. Interfering the glycolysis pathway may be a valuable antitumor strategy. This study aimed to assess the effect of NDV on the glycolysis pathway in infected breast cancer cells. Oncolytic NDV attenuated AMHA1 strain was used in this study. AMJ13 and MCF7 breast cancer cell lines and a normal embryonic REF cell line were infected with NDV with different multiplicity of infections (moi) to determine the IC50 of NDV through MTT assay. Crystal violet staining was done to study the morphological changes. NDV apoptosis induction was assessed using AO/PI assay. NDV interference with the glycolysis pathway was examined through measuring hexokinase (HK) activity, pyruvate, and ATP concentrations, and pH levels in NDV infected and non-infected breast cancer cells and in normal embryonic cells. The results showed that NDV replicates efficiently in cancer cells and spare normal cells and induce morphological changes and apoptosis in breast cancer cells but not in normal cells. NDV infected cancer cells showed decreased in the HK activity, pyruvate and ATP concentrations, and acidity, which reflect a significant decrease in the glycolysis activity of the NDV infected tumor cells. No effects on the normal cells were observed. In conclusion, oncolytic NDV ability to reduce glycolysis pathway activity in cancer cells can be an exciting module to improve antitumor therapeutics.

Attenuated measles vaccine strain have potent oncolytic activity against Iraqi patient derived breast cancer cell line.

BACKGROUND: One of the world's leading causes of death among females is breast cancer. Oncolytic viruses are promising anticancer therapy that can overcome resistance to current conventional therapies. Measles virus replicates in and destroys malignant cells without affecting healthy cells. The study aimed to evaluate the lives attenuated Measles virus vaccine against Iraqi patient derived breast cancer cells that have functional BRCA1/BRCA2 genes and compare its activity against international breast cancer MCF-7 and CAL-51 cell lines. METHODS: The virus was propagated in VERO-hSLAM slam cells. The MTT cytotoxicity assay used to test the virus's ability to kill three human breast cell lines (AMJ13), (MCF-7), and (CAL-51). The cytopathic effect of the measles virus was determined using an H&E stain. Immunocytochemistry assay using specific anti H protein monoclonal antibody for measles virus in the virally infected cells. Finally, apoptosis induction in the infected cells tested using double staining of acridine orange/propidium iodide. RESULTS: The result shown that breast cancer cells are effectively infected and destroyed by live attenuated measles virus vaccine, and it caused a significant cytopathic effect in the infected cell lines after 48-72 h of infection with remarkable effect on AMJ13 cells (IC50 was 3.527 for AMJ13, when it was 5.079 and 9.171 for MCF-7 and CAL-51 respectively). Measles virus treatment induces apoptosis significantly in breast cancer cell lines compared with control cells. CONCLUSION: MeV vaccine is useful and safe as anticancer therapy with a notable impact on the local Iraqi breast cancer AMJ13 cells.

Outcome of salvage ureteral reimplantation after endoscopic treatment failure for high-grade vesicoureteral reflux compared to primary ureteral reimplantation.

INTRODUCTION: Surgical treatment of vesicoureteral reflux is required after conservative treatment has failed. However, there is a controversy if fibrosis related to previous attempts of dextranomer/hyaluronic acid (Dx/Ha) injection increases the risk of surgical difficulty and postoperative complications. Therefore, the purpose of our study was to compare the outcome of salvage ureteral reimplantation (SUR), after failed endoscopic therapy, to that of primary ureteral reimplantation in patients with high-grade primary vesicoureteral reflux (VUR). MATERIALS AND METHODS: We conducted a retrospective analysis of children, <14 years old, treated for Grade IV or V VUR, between 1998 and 2014. Cases were classified into the SUR or the PUR group. Cases of secondary VUR were excluded. All patients were treated using a cross-trigonal ureteral reimplantation technique by two surgeons. The following demographic and clinical variables were included in the analysis: presentation, reflux severity, scarring on imaging, age at endoscopic injection, total amount of Dx/Ha injected, operative time, postoperative hospital stay, operative complications, incidence of febrile urinary tract infections (UTIs) after surgery, and persistent VUR. Between the groups, differences were evaluated using Fisher's exact test. RESULTS: Twenty-six patients were included, 19 in the SUR and 7 in the primary ureteral reimplantation (PUR) group. In the SUR group, 12 cases had a bilateral VUR and 7 had a unilateral VUR, with 4 bilateral and 3 unilateral VUR cases in the PUR group. In the SUR group, 13 patients had received one Dx/Ha injections, with the other 6 receiving two injections, of 0.5 ml of Dx/Ha (range, 0.5-2.0 ml). A bilateral reimplantation was performed in 14/19 patients in the SUR group and 4/7 in the PUR group. The median age at surgery was 4 years in the SUR group and 3 years in the PUR group (P < 0.02). The median operative time was comparable between the groups (120 and 140 min for the SUR and PUR groups, respectively, P = 0.73), with a comparable length of hospital stay (5 and 6 days, respectively, P = 0.061). Blood loss was generally <10 ml, except in three cases in the SUR group, due to difficult dissection. Over the median follow-up of 1 year, persistent Grade III SUR was identified in only one patient in the SUR group, with no occurrence of febrile UTIs postoperatively. CONCLUSION: SUR for high-grade primary VUR after failed Dx/Ha injection has the same success rate as PUR, with no significant complication rate, although the necessary dissection may be more difficult.

Combined therapy of oncolytic Newcastle disease virus and rhizomes extract of Rheum ribes enhances cancer virotherapy in vitro and in vivo.

Phytotherapy has been used to treat a different type of diseases including cancer for a long time, and it was a source for different active anti-tumor agents. Oncolytic Newcastle disease virus (AMHA1) are very promising anti-tumor therapy. Nevertheless, NDV-based monotherapeutics have not been very useful to some resistant tumors. Thus, the efficiency of oncolytic NDV must enhance by combining NDV with other novel therapies. The current study aimed to determine the possibility of improving the oncolytic effect induced by NDV through Rheum ribes rhizomes extract administration in vitro and in vivo. Methods, the in vitro study include exposure of the crude extract of Rheum ribes alone or NDV alone or combination of both agents for 72 h. The cancer cells tested were murine mammary adenocarcinoma AMN3, Human Rhabdomyosarcoma RD, and Human Glioblastoma AMGM5, and using rat embryo fibroblast REF as normal control cells. MTT cell viability assay was used and analyzed for possible synergism using the Chou-Talalay analysis method. In vivo experiment included study the combination and the monotherapeutic modalities in the transplanted murine mammary adenocarcinoma AM3 line and tumor sections analyzed by histopathology. Results, Combination therapy of NDV-R. ribes showed enhanced oncolytic activity on cancer cells. With no cytotoxicity on normal cells. In vivo study showed that monotherapeutic modalities had lower growth inhibitory effect on transplanted tumors in mice in compare to combination therapy. Histopathological examination revealed the broader area of necrosis in tumors treated by combination therapy. In conclusion, the novel combination recommended for clinical application for cancer therapy.