scholarly journals Anti-leukemic activity of phosphoproteins from Sesamin via induction of nuclear antigen H731and CLIP-associating protein 2 isoform X25 mediated apoptosis

2017 ◽  
Vol 9 (2) ◽  
Author(s):  
Pattharin Wannapruk ◽  
Atchara Paemanee ◽  
Sittiruk Roytrakul ◽  
Dalina I Tanyong
Keyword(s):  
Cancer Cells ◽  
Sesame Seed ◽  
Interaction Network ◽  
Leukemic Cell ◽  
Leukemic Cells ◽  
Nuclear Antigen ◽  
Therapeutic Drug ◽  
Ligand Interaction ◽  
Biological Regulation ◽  
Leukemic Cell Lines

<p>Leukemia is an uncontrolled proliferation hematopoietic cancer cells that commonly treats with conventional therapies such as chemotherapy. However, many side effects were reported. Alternative medicines have been developed by using natural or herb compounds as therapeutic drug. Sesamin, a class of phytoestrogen isolated from sesame seed displaying potent anticancer activity in <em>vitro</em> and in <em>vivo</em>.However, the mechanism by which <em>sesamin</em> mediates <em>anticancer</em> effects on leukemic cells are notfully understood. In thisstudy, the effects of sesamin on cell viability, cell apoptosis and expression of phosphoproteins in Molt-4 and NB4 leukemic cell lines were investigated using MTT assay, flow cytometry and immobilized metal affinity chromatography (IMAC) phosphoprotein enrichment and LC-MS, respectively. The results showed that sesamin reduced viability and induced apoptosis in leukemic cells. In addition, 79 phosphoproteins were identified from LC-MS within three main clusters including biological regulation, cellular processand metabolic process. Interestingly, nuclear antigen H731 (PDCD4) and CLIP-associating protein 2 isoform X25 (CLASP2) showed increased in sesamin treated cells and associated protein-ligand interaction network with allicin, capsaicin, cucurbitacin B, and rapamycin which are known to activate <em>apoptosis</em> in <em>cancer cells</em>.Then, sesamin could be developed as candidate of alternative leukemia treatment  in the future.</p>

Apoptosis of leukemic cells accompanies reduction in intracellular pH after targeted inhibition of the Na+/H+exchanger

Blood ◽  
2000 ◽  
Vol 95 (4) ◽  
pp. 1427-1434 ◽  
Author(s):  
Ivan N. Rich ◽  
Diana Worthington-White ◽  
Oliver A. Garden ◽  
Philip Musk
Keyword(s):  
Cell Cycle ◽  
Intracellular Ph ◽  
Annexin V ◽  
Leukemic Cell ◽  
Differential Sensitivity ◽  
Leukemic Cells ◽  
Hematopoietic Tissue ◽  
Leukemic Cell Lines ◽  
Targeted Inhibition

The Na+/H+ exchanger isoform 1 (NHE1) is primarily responsible for the regulation of intracellular pH (pHi). It is a ubiquitous, amiloride-sensitive, growth factor–activatable exchanger whose role has been implicated in cell-cycle regulation, apoptosis, and neoplasia. Here we demonstrate that leukemic cell lines and peripheral blood from primary patient leukemic samples exhibit a constitutively and statistically higher pHi than normal hematopoietic tissue. We then show that a direct correlation exists between pHi and cell-cycle status of normal hematopoietic and leukemic cells. Advantage was taken of this relationship by treating leukemic cells with the Na+/H+ exchanger inhibitor, 5-(N, N-hexamethylene)-amiloride (HMA), which decreases the pHiand induces apoptosis. By incubating patient leukemic cells in vitro with pharmacologic doses of HMA for up to 5 hours, we show, using flow cytometry and fluorescent ratio imaging microscopy, that when the pHi decreases, apoptosis—measured by annexin-V and TUNEL methodologies—rapidly increases so that more than 90% of the leukemic cells are killed. The differential sensitivity exhibited between normal and leukemic cells allows consideration of NHE1 inhibitors as potential antileukemic agents.

Differential expression of a novel proline-rich homeobox gene (Prh) in human hematolymphopoietic cells

Blood ◽  
1995 ◽  
Vol 85 (5) ◽  
pp. 1237-1245 ◽  
Author(s):  
G Manfioletti ◽  
V Gattei ◽  
E Buratti ◽  
A Rustighi ◽  
A De Iuliis ◽  
...  
Keyword(s):  
Cell Lines ◽  
Constitutive Expression ◽  
Leukemic Cell ◽  
Leukemic Cells ◽  
Maturation Stage ◽  
Lymphoid Tissues ◽  
Specific Cell ◽  
B Cell Differentiation ◽  
Leukemic Cell Lines

Proline-rich homeobox (Prh) is a novel human homeobox-containing gene recently isolated from the CD34+ cell line KG-1A, and whose expression appears mainly restricted to hematopoietic tissues. To define the pattern of Prh expression within the human hematopoietic system, we have analyzed its constitutive expression in purified cells obtained from normal hematopoietic tissues, its levels of transcription in a number of leukemia/lymphoma cell lines representing different lineages and stages of hematolymphopoietic differentiation, and its regulation during in vitro maturation of human leukemic cell lines. Prh transcripts were not detected in leukemic cells of T-lymphoid lineage, irrespective of their maturation stage, and in resting or activated normal T cells from peripheral blood and lymphoid tissues. In contrast, high levels of Prh expression were shown in cells representing early stages of B lymphoid maturation, being maintained up to the level of circulating and tissue mature B cells. Terminal B-cell differentiation appeared to be conversely associated with the deactivation of the gene, since preplasmacytic and plasmocytoma cell lines were found not to express Prh mRNA. Prh transcripts were also shown in human cell lines of early myelomonocytic, erythromegakaryocytic, and preosteoclast phenotypes. Prh expression was lost upon in vitro differentiation of leukemic cell lines into mature monocyte-macrophages and megakaryocytes, whereas it was maintained or upregulated after induction of maturation to granulocytes and osteoclasts. Accordingly, circulating normal monocytes did not display Prh mRNA, which was conversely detected at high levels in purified normal granulocytes. Our data, which show that the acquisition of the differentiated phenotype is associated to Prh downregulation in certain hematopoietic cells but not in others, also suggest that a dysregulated expression of this gene might contribute to the process of leukemogenesis within specific cell lineages.

scholarly journals Signal transduction and glycophosphatidylinositol-linked proteins (lyn, lck, CD4, CD45, G proteins, and CD55) selectively localize in Triton- insoluble plasma membrane domains of human leukemic cell lines and normal granulocytes

Blood ◽  
1996 ◽  
Vol 87 (9) ◽  
pp. 3783-3794 ◽  
Author(s):  
I Parolini ◽  
M Sargiacomo ◽  
MP Lisanti ◽  
C Peschle
Keyword(s):  
Signal Transduction ◽  
G Proteins ◽  
Cell Lines ◽  
Tyrosine Kinases ◽  
Leukemic Cell ◽  
Receptor Activation ◽  
Leukemic Cells ◽  
Human Leukemic Cell ◽  
Leukemic Cell Lines ◽  
B Lymphoid

Src-family nonreceptor protein tyrosine kinases (NRPTK) are associated with cell surface receptors in large detergent-resistant complexes: in epithelial cells, yes is selectively located in vesicle structures containing caveolin (“caveolae”). These formations are typically also endowed with glycophosphatidylinositol (GPI)-anchored proteins. In the present study, we observed lck, lyn, src, hck, CD4, CD45, G proteins, and CD55 (decay-accelerating factor) expression in the buoyant low- density Triton-insoluble (LDTI) fraction of selected leukemic cell lines and granulocytes. We provide a detailed analysis of the two most highly expressed NRPTK, p53/p56lyn and p56lck, which are involved in the transduction of signals for proliferation and differentiation of monocytes/B lymphocytes and T lymphocytes, respectively. We show that lyn is selectively recovered in LDTI complexes isolated from human leukemic cell lines (promyelocytic [HL-60], erythroid [K562] and B- lymphoid [697]) and from normal human granulocytes, and that lck is recovered from LDTI fractions of leukemic T- and B-lymphoid cell lines (CEM, 697). In LDTI fractions of leukemic cells, lck and lyn are enriched 100-fold as compared with the total cell lysates. Analysis of these fractions by electron microscopy shows the presence of 70- to 200- nm vesicles: lyn and lck are homogenously distributed in the vesicles, as revealed by an immunogold labeling procedure. These novel results propose a role for these vesicles in signal transduction mechanisms of normal and neoplastic hematopoietic cells. In support of this hypothesis, we further observed that molecules participating in B- and T-cell receptor activation cofractionate in the LDTI fractions, CD45/lyn (B cells) and CD45/lck/CD4 (T cells).

scholarly journals Loss of suppression of normal bone marrow colony formation by leukemic cell lines after differentiation is induced by chemical agents

Blood ◽  
1985 ◽  
Vol 65 (1) ◽  
pp. 100-106 ◽  
Author(s):  
HN Steinberg ◽  
AS Tsiftsoglou ◽  
SH Robinson
Keyword(s):  
Bone Marrow ◽  
Cell Lines ◽  
Colony Formation ◽  
Leukemic Cell ◽  
K562 Cells ◽  
Leukemic Cells ◽  
Cell Phenotype ◽  
Normal Bone Marrow ◽  
Normal Bone ◽  
Leukemic Cell Lines

Abstract The human leukemic cell lines K562 and HL-60 were cocultured with normal bone marrow (BM) cells. Coculture with 10(4) K562 or HL-60 cells results in 50% inhibition of normal CFU-E and BFU-E colony formation. However, when the same number of K562 and HL-60 cells is first treated for two to five days with agents that induce their differentiation, a gradual loss in their capacity to inhibit CFU-E and BFU-E colony formation is observed. The inhibitory material in K562 cells is soluble and present in conditioned medium from cultures of these cells. The degree to which leukemic cell suppression of CFU-E and BFU-E growth is reversed is correlated with the time of exposure to the inducing agent. Suppression is no longer evident after five days of prior treatment with inducers. In fact, up to a 90% stimulation of CFU-E growth is observed in cocultures with K562 cells that have been pretreated with 30 to 70 mumol/L hemin for five days. K562 cells treated with concentrations of hemin as low as 30 mumol/L demonstrate increased hemoglobin synthesis and grow normally, but no longer have an inhibitory effect on CFU-E growth. Hence, reversal of normal BM growth inhibition must be caused by the more differentiated state of the K562 cells and not by a decrease in the number of these cells with treatment. Thus, induction of differentiation in cultured leukemic cells not only alters the malignant cell phenotype but also permits improved growth of accompanying normal marrow progenitor cells. Both are desired effects of chemotherapy.

Pioglitazone Inhibits the Growth of Human Leukemic Cell Lines and Primary Leukemic Cells in Vitro.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4493-4493 ◽  
Author(s):  
Yoshihiro Hatta ◽  
Minoru Saiki ◽  
Yuko Enomoto ◽  
Shin Aizawa ◽  
Umihiko Sawada ◽  
...  
Keyword(s):  
Cell Lines ◽  
Colony Formation ◽  
Mononuclear Cells ◽  
Hematopoietic Cells ◽  
Leukemic Cell ◽  
Leukemic Cells ◽  
Peroxisome Proliferator ◽  
Leukemic Cell Lines ◽  
Ppar Γ

Abstract Troglitazone and pioglitazone are one of thiazolidinediones that are high affinity ligand for the nuclear receptor called peroxisome proliferator-activated receptor gamma (PPAR-γ). Troglitazone is a potent inhibitor of clonogenic growth of acute myeloid leukemia cells when combined with a retinoid. However, the effect of pioglitazone to neoplastic cells and normal hematopoietic cells has not been studied yet. Adult T-cell leukemia (ATL), prevalent in western Japan, is a highly aggressive malignancy of mature T lymphocyte. Therefore, we studied antitumor effect of pioglitazone against leukemic cells including ATL as well as normal hematopoietic cells. With 300 μM of pioglitazone, colony formation of ATL cell lines (MT1, MT2, F6T, OKM3T, and Su9T01) was completely inhibited. Colony formation of HUT102, another ATL cell line, was 12 % compared to untreated control. Clonogenic cells of other leukemic cell lines (K562, HL60, U937, HEL, CEM, and NALM1) was also inhibited to 0–30% of control. Colony formation of primary leukemic cells from 5 AML patients was decreased to 15 %. However, normal hematopoietic cells were weakly inhibited with 300 μM pioglitazone; 77 % of CFU-GM, 70 % of CFU-E, and 33 % of BFU-E survived. Cell cycle analysis showed that pioglitazone decreased the ratio of G2/M phase in HL60 cells, suggesting the inhibition of cell division. By Western blotting, PPAR-γ protein level was similar in all leukemic cells and normal bone marrow mononuclear cells. Taken together, pioglitazone effectively eliminate leukemic cells and could be used as an antitumor agent in vivo.

Expression of Vascular Endothelial-Cadherin on Leukemic Cells Mediates Their Interaction with Vascular Endothelium.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2761-2761
Author(s):  
Leslie R. Ellis ◽  
Loic Vincent ◽  
Sergey Shmelkov ◽  
Andrea Hooper ◽  
Scott Avecilla ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Minimal Residual Disease ◽  
Cell Lines ◽  
Residual Disease ◽  
Leukemic Cell ◽  
Angiogenic Factors ◽  
Leukemic Cells ◽  
Vascular Endothelial ◽  
Leukemic Cell Lines ◽  
Minimal Residual

Abstract It has already been established that subsets of leukemic cells express receptors for pro-angiogenic factors, such as vascular endothelial growth factor receptor-2 (VEGFR-2). Further studies have shown that these same leukemic cells also produce the ligand for these VEGF receptors, VEGF-A. This autocrine loop supports the invasion and proliferation of these particular leukemic cells. The VEGFR-2 signaling pathway is further dependent upon the co-activation of other pro-angiogenic factors, such as vascular endothelial (VE)-cadherin. VE-cadherin is an endothelial cell-specific transmembrane cellular adhesion protein that when bound results in the dephosphorylation of VEGFR-2 and contributes to neo-vessel formation. Recent studies have suggested that VE-cadherin may be expressed by a unique subset of hematopoietic cells, raising the possibility that leukemic cells may express VE-cadherin as well. We therefore sought to identify the expression of VE-cadherin on leukemic cell lines and primary samples, and further determine its role in the interaction with VE-cadherin-positive endothelial cells. Leukemic cell lines and primary leukemias were screened for the presence of VE-cadherin by both RT-PCR and Western blot analysis. Primary leukemic samples, as well as established cell lines for human erythroblastic leukemia (HEL) and acute myelogenous leukemia (KG-1a) were found to express VE-cadherin. VE-cadherin expression was further confirmed by flow cytometry and immunocytochemistry, which demonstrated that approximately 15% of the total population was VE-cadherin-positive. Proliferation and migration assays utilizing neutralizing monoclonal antibodies to VE-cadherin were performed with no obvious effects. However, immunofluorescent staining of a co-culture performed with the above leukemic cells grown on a layer of human umbilical vein endothelial cells (HUVECs) demonstrated that the leukemic cells and HUVECs interact via VE-cadherin. Furthermore, when these leukemic cells were injected into NOD-SCID mice subcutaneously, the VE-cadherin-positive cells localized around the vessels present within the leukemic chloroma. These data set forth the concept that a subset of leukemic cells expresses the protein VE-cadherin and that VE-cadherin is involved in the cell-to-cell interaction between a subset of leukemic cells and vascular endothelial cells. Heterotypic VE-cadherin interaction between leukemic cells and neo-vessels may increase the survival of leukemic cells and contribute to the generation of minimal residual disease. Therefore, inhibition of VEGFR-2 in conjunction with VE-cadherin may provide a novel strategy to eradicate minimal residual disease.

Expression and Function of the CXCR7 Chemokine Receptor in Leukemias

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2423-2423
Author(s):  
Sergej Konoplev ◽  
Hongbo Lu ◽  
Michael A Fiegl ◽  
Zhihong Zeng ◽  
Wenjing Chen ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Cell Lines ◽  
Lymphoblastic Leukemia ◽  
Leukemic Cell ◽  
Leukemic Cells ◽  
Human Leukemia ◽  
Rt Pcr ◽  
Hematopoietic Stem ◽  
Leukemic Cell Lines ◽  
And Function

Abstract Background: Bone marrow produced stromal-derived factor-1a (SDF-1a) is a key chemokine involved in chemotaxis, homing, mobilization, and expansion of hematopoietic stem and progenitor cells. While the majority of well-defined functions of SDF-1a are mediated via its receptor CXCR4, recent studies have characterized CXCR7 as an alternative receptor capable of binding SDF-1a. Although the functions of CXCR7 are still incompletely understood, the receptor was reported to promote migration and adhesion in certain cell types and function as a pro-survival factor in breast cancer cells. CXCR7 expression and function in human leukemia cells has not been characterized. In this study, we examined CXCR7 expression in leukemia cell lines and primary samples from patients with acute lymphoblastic leukemia (ALL) and utilized a small molecule inhibitor of CXCR7 to probe CXCR7’s function. Materials and methods: CXCR4 and CXCR7 expression was determined by flow cytometry, real-time PCR (RT-PCR) and immunocytochemistry (ICC) in leukemic cell lines including AML (OCI-AML2, OCI-AML3, HL60, U937 NB4, Molm13), ALL (REH, Raji, RS4; 11, Nalm6, Molt4) and CML (KBM5, K562) cells. In primary ALL patient samples, CD34+CD19+ gating was applied to detect CXCR7 expression on pre-B leukemic cells by flow cytometry. The migration of leukemic cells towards SDF-1a was studied using a transwell system. CXCR4 inhibitor AMD3100 was purchased from Sigma, and CXCR7 inhibitor CCX-733 was provided by ChemoCentryx Inc., Mountain View, CA. Results: CXCR4 was found to be ubiquitously expressed on the cell surface of all leukemic cell lines tested. CXCR7 mRNA and protein expression was detectable only in Burkitt lymphoma Raji cells, as analyzed by flow cytometry (clone 11G8, R&D systems), RT-PCR and ICC. Curiously, CXCR7 expression was significantly induced in MOLM13 cells under hypoxic (6% O2) conditions (p=0.01). Low levels of surface CXCR7 were found in 8 of the 9 primary ALL samples by flow cytometry. To determine the respective roles of CXCR4 and CXCR7 in migration of leukemic cells, we utilized CXCR4 inhibitor AMD3100 and CXCR7 inhibitor CCR733 in Raji (CXCR7 positive) and RS4;11 (CXCR7 negative) cells. AMD3100 at 25μM significantly inhibited SDF-1a induced migration (from 38.5% to 12%); CCR733 at 10μM also inhibited SDF-1a induced migration (from 38.5% to 24%) and the combination of AMD3100 and CCR733 resulted in 81% inhibition of migration (from 38.5% to 7.2%). AMD3100 blocked SDF-1a induced migration of CXCR4+CXCR7− RS4;11 cells (from 36.5% to 15.8%), while CCR733 had no effect (36.5% and 39.2%). In conclusion, these studies demonstrate functional expression of the SDF-1 receptor CXCR-7 on Raji and primary ALL cells and suggest that CXCR7 plays an active role in the migration of leukemic cells. CXCR-7 may serve as an alternative receptor to CXCR4. Studies addressing the role of CXCR7 in adhesion, SDF-1a-mediated signaling and survival of leukemic cells are in progress.

Chemoprevention Against Hepatocellular Carcinoma of Cornus officinalis in vitro

2004 ◽  
Vol 32 (05) ◽  
pp. 717-725 ◽  
Author(s):  
Jung-San Chang ◽  
Lien-Chai Chiang ◽  
Fen-Fang Hsu ◽  
Chun-Ching Lin
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Lines ◽  
Leukemic Cell ◽  
Leukemic Cells ◽  
Xtt Assay ◽  
Leukemic Cell Lines ◽  
Cornus Officinalis ◽  
Anti Oxidant ◽  
Dose Dependent

The water extracts of Cornus officinalis Sieb. et Zuce against hepatocellular carcinoma (HCC) was studied for its chemopreventive potential. Three HCC cell lines (HepG2, SK-Hep1 and PLC/PRF/5) and three leukemic cell lines (U937, K562 and Raji) were tested with XTT assay. Extracts of C. officinalis inhibited all these HCC cells and leukemic cells at a concentration of 100 μg/ml (P<0.05) and was dose-dependent (P<0.0001). P53 (P<0.0001) and Ras (P=0.001) significantly affected its activity against HCC. Extracts of C. officinalis also possessed the anti-oxidant activity through free radicals scavenging activity at a concentration of 50 μg/ml (P<0.05). In summary, our experiment implied that C. officinalis might be a candidate for chemopreventive agent against HCC through the antioxidant and anti-neoplastic effects.

scholarly journals Co-Treatments of Edible Curcumin from Turmeric Rhizomes and Chemotherapeutic Drugs on Cytotoxicity and FLT3 Protein Expression in Leukemic Stem Cells

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5785
Author(s):  
Fah Chueahongthong ◽  
Singkome Tima ◽  
Sawitree Chiampanichayakul ◽  
Cory Berkland ◽  
Songyot Anuchapreeda
Keyword(s):  
Stem Cells ◽  
Protein Expression ◽  
Cell Lines ◽  
Synergistic Effects ◽  
Leukemic Cell ◽  
Leukemic Cells ◽  
Dependent Manner ◽  
Chemotherapeutic Drugs ◽  
Protein Levels ◽  
Leukemic Cell Lines

This study aims to enhance efficacy and reduce toxicity of the combination treatment of a drug and curcumin (Cur) on leukemic stem cell and leukemic cell lines, including KG-1a and KG-1 (FLT3+ LSCs), EoL-1 (FLT3+ LCs), and U937 (FLT3− LCs). The cytotoxicity of co-treatments of doxorubicin (Dox) or idarubicin (Ida) at concentrations of the IC10–IC80 values and each concentration of Cur at the IC20, IC30, IC40, and IC50 values (conditions 1, 2, 3, and 4) was determined by MTT assays. Dox–Cur increased cytotoxicity in leukemic cells. Dox–Cur co-treatment showed additive and synergistic effects in several conditions. The effect of this co-treatment on FLT3 expression in KG-1a, KG-1, and EoL-1 cells was examined by Western blotting. Dox–Cur decreased FLT3 protein levels and total cell numbers in all the cell lines in a dose-dependent manner. In summary, this study exhibits a novel report of Dox–Cur co-treatment in both enhancing cytotoxicity of Dox and inhibiting cell proliferation via FLT3 protein expression in leukemia stem cells and leukemic cells. This is the option of leukemia treatment with reducing side effects of chemotherapeutic drugs to leukemia patients.

scholarly journals AN INTEGRATIVE APPROACH DISCOVERS A NOVEL ANTI-LEUKEMIC PEPTIDE FROM HUMAN MILK

2021 ◽  
Author(s):  
Wararat Chiangjong ◽  
Jirawan Panachan ◽  
Thitinee Vanichapol ◽  
Nutkridta Pongsakul ◽  
Tassanee Lerksuthirat ◽  
...  
Keyword(s):  
Childhood Leukemia ◽  
Leukemic Cell ◽  
Helical Structure ◽  
Leukemic Cells ◽  
Integrative Approach ◽  
Human Breast Milk ◽  
Dependent Manner ◽  
Leukemic Cell Lines ◽  
Late Morbidity

AbstractChemotherapy in childhood leukemia is associated with late morbidity in leukemic survivors, while certain patient subsets relatively resistant to standard chemotherapy. Identifying new agents with the sensitivity and selectivity toward leukemic cells with less systemic toxicity is a warrant. Peptide-based therapeutics is gaining attention during the last few years. Here, we used an integrative workflow combining mass spectrometric peptide library construction, in silico anticancer peptide screening, and in vitro leukemic cell studies to discover a novel anti-leukemic peptide owning 3+charges and alpha-helical structure, namely HMP-S7, from human breast milk. HMP-S7 showed cytotoxic activity against four distinct leukemic cell lines in a dose-dependent manner but had no affected on solid malignancies or representative normal cells. HMP-S7 induced leukemic cell death by penetrating the plasma membrane into the cytoplasm, causing lactate dehydrogenase leakage, thereby defining membranolytic action. In conclusion, HMP-S7 is the selective anti-leukemic peptide promising for further validation in preclinical and clinical studies.

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