THE EFFECTS OF RETINOIC ACID ON EXPRESSION OF C-MYC, C-FOS IN LEUKEMIC PROMYELOCYTES

The expression of c-myc, c-fos of leukemic promyelocytes (HL-60 and acute promyelocytic leukemia cells) from 18 acute promyelocytic leukemia (APL) patients treated with all-trans retinoic acid (RA) in vitro was studied. There was no expression of c-fos in HL-60 cells and APL cells from 17 patients. But in one case, a slight expression of c-fos in leukemic cells was observed, and the alteration of expression level was found during the treatment of the cells with RA in vitro. The expression of c-myc in HL-60 cells induced by RA was altered, decrease in the early, increase in the middle, and decline in the later stage were found. The c-myc expression in leukemic cells of eighteen APL patients was variable. There was c-myc expression in eleven APL cells, but no expression in the others. The APL cells with c-myc expression were treated with RA in vitro to observe the kinetic changes of c-myc RNA level. The results showed that the expression of c-myc was gradually decreased except in few cases. Using in situ hybridization technique for detecting the alteration of c-myc expression in leukemic cells of two APL patients. the high level of c-myc before RA treatment and low level of c-myc expression after obtaining complete remission induced by RA were found. The possibility of different proto-oncogenes implicated differentiation was discussed.

Carrimycin in the treatment of acute promyelocytic leukemia combined with pulmonary tuberculosis: A case report

BACKGROUND Pulmonary tuberculosis(PTB)is prevalent in immunocompromised populations,including patients with hematologic malignancies,human immunodeficiency virus infections,and chronic diseases.Effective treatment for acute promyelocytic leukemia(APL)combined with PTB is lacking.These patients show an extremely poor prognosis.Therefore,studies should establish efficient treatment options to improve patient survival and prognosis.CASE SUMMARY A 60-year-old male with pain in the right side of his chest and a fever for 4 d visited the outpatient department of our hospital.Peripheral blood smear revealed 54%blasts.Following bone marrow examinations,variant APL with TNRC18-RARA fusion gene was diagnosed.Chest computed tomography scan showed bilateral pneumonitis with bilateral pleural effusions,partial atelectasis in the lower lobes of both lungs,and the bronchoalveolar lavage fluid gene X-Pert test was positive,indicative of PTB.Carrimycin,ethambutol(EMB),and isoniazid(INH)were administered since he could not receive chemotherapy as the WBC count decreased continuously.After one week of treatment with carrimycin,the patient recovered from fever and received chemotherapy.Chemotherapy was very effective and his white blood cells counts got back to normal.After being given five months with rifampin,EMB and INH and chemotherapy,the patient showed complete remission from pneumonia and APL.CONCLUSION We report a case of PTB treated successfully with carrimycin with APL that requires chemotherapy.

CD71-mediated liposomal arsenic-nickel complex combined with all-trans retinoic acid for the efficacy of acute promyelocytic leukemia

Clinically,arsenic trioxide(ATO)was applied to the treatment of acute promyelocytic leukemia(APL)as a reliable and effective frontline drug.However,the administration regimen of AsⅢwas limited due to its fast clearance,short therapeutic window and toxicity as well.Based on CD71 overexpressed on APL cells,in present study,a transferrin(Tf)-modified liposome(LP)was established firstly to encapsulate AsⅢin arsenic-nickel complex by nickel acetate gradient method.The AsⅢ-loaded liposomes(AsLP)exhibited the feature of acid-sensitive release in vitro.Tf-modified AsLP(Tf-AsLP)were specifically taken up by APL cells and the acidic intracellular environment triggered liposome to release AsⅢwhich stimulated reactive oxygen species level and caspase-3 activity.Tf-AsLP prolonged half-life of AsⅢin blood circulation,lowered systemic toxicity,and promoted apoptosis and induced cell differentiation at lesion site in vivo.Considering that ATO combined with RA is usually applied as the first choice in clinic for APL treatment to improve the therapeutic effect,accordingly,a Tf-modified RA liposome(Tf-RALP)was designed to reduce the severe side effects of free RA and assist Tf-AsLP for better efficacy.As expected,the tumor inhibition rate of Tf-AsLP was improved significantly with the combination of Tf-RALP on subcutaneous tumor model.Furthermore,APL orthotopic NOD/SCID mice model was established by 60CO irradiation and HL-60 cells intravenously injection.The effect of co-administration(Tf-AsLP+Tf-RALP)was also confirmed to conspicuous decrease the number of leukemia cells in the circulatory system and prolong the survival time of APL mice by promoting the APL cells’apoptosis and differentiation in peripheral blood and bone marrow.Collectively,Tf-modified acid-sensitive AsLP could greatly reduce the systemic toxicity of free drug.Moreover,Tf-AsLP combined with Tf-RALP could achieve better efficacy.Thus,transferrinmodified AsⅢliposome would be a novel clinical strategy to improve patient compliance,with promising translation prospects.

Atypical Hemolytic Uremic Syndrome in a Patient with Acute Promyelocytic Leukemia: A Case Report

Introduction: Acute Promyelocytic Leukemia (APL) is highly associated with hemostasis alterations. The atypical hemolytic uremic syndrome (aHUS) is a rare type of Thrombotic Microangiopathy (TMA) due to an overactivation of the alternative complement pathway. Case Presentation: A 48-years-old woman was diagnosed with APL and achieved molecular remission after induction therapy. During the second consolidation cycle she presented with TMA. She began treatment with plasma exchange plus corticotherapy but due to aggravation of symptoms Eculizumab was initiated. Thrombotic thrombocytopenic purpura, infections and drug toxicity causes were ruled out. There was no evidence of relapse of the APL. Genetic studies of the hereditary anomalies of the alternative complement pathway were negative and the decision of stopping Eculizumab was made. During maintenance therapy for the APL she presented a severe relapse of the aHUS, requiring dialysis. She re-started treatment with Eculizumab with a progressive hematologic recovery and improvement of renal function. She completed APL treatment without relapse of the leukemia for the moment and continues to be treated with Eculizumab. Conclusion: This is the first published case of coexisting aHUS and APL successfully treated with Eculizumab.

EFFECTS OF PML AND PML/RMRα ANTISENCE OLIGO-NUCLEOTIDE ON PROMYELOCYTIC LEUKEMIA CELL NB4

Objective: To investigate the effects of anti-PML (promyelocytic leukemia) or anti-PML/RAR( (promyelocytic leukemia/retionic acid receptor() antisense oligonucleotides on cell growth, expression of PML-RAR( mRNA and PML-RAR(/PML protein location of NB4 cell lines. Methods: RT-PCR was used for detecting PML-RAR( mRNA expression, trypan blue exclusion for cell count, methylcellose assay for leukemic colony forming unit detection, immuno- fluorescence for PML-RAR(/PML protein location. Results: Both anti-PML start codon region antisence (STAS) and anti-PML-RAR( fusion region antisence (FUAS) could inhibit cell growth and the formation of acute myelocytic colony forming unit of cells(AML-CFU). Cells become partial differentiated at days 5, being more obvious in FUAS-treated cells than in STAS ones. Down regulation of PML-RAR( mRNA expression occurred at 24 hours in STAS and FUAS-treated cells and maintained for up to 72 hours. Immuno-fluorescence analysis with anti-PML monoclonal antibody showed a remarkable decrease even complete disappearance of microgranules. The residual granules became enlarged as discrete dots (<10 per cell), similar to normal POD structure in some STAS-treated cells at 24 hours. At 72 hours, nearly all the granules disappeared. Similar changes were observed in FUAS-treated cells. Conclusion: Both PML and PML-RAR( antisence oligonucleotides can specially block the expression of PML-RAR( at mRNA and protein levels. PML protein is implicated in the regulations of cell differentiation.

E2FBP1 antagonizes the p16^(INK4A)-Rb tumor suppressor machinery for growth suppression and cellular senescence by regulating promyelocytic leukemia protein stability

Cellular senescence is an irreversible cell cycle arrest triggered by the activation of oncogenes or mitogenic signaling as well as the enforced expression of tumor suppressors such as p53, p16INK4A and promyelocytic leukemia protein （PML） in normal cells. E2F-binding protein 1 （E2FBP1）, a transcription regulator for E2F, induces PML reduction and suppresses the formation of PML-nuclear bodies, whereas the down-regulation of E2FBP1 provokes the PML-dependent premature senescence in human normal fibroblasts. Here we report that the depletion of E2FBP1 induces the accumulation of PML through the Ras-dependent activation of MAP kinase signaling. The cellular levels of p16INK4A and p53 are elevated during premature senescence induced by depletion of E2FBP1, and the depletion of p16INK4A, but not p53 rescued senescent cells from growth arrest. Therefore, the premature senescence induced by E2FBP1 depletion is achieved through the pl6INK4A-Rb pathway. Similar to human normal fibroblasts, the growth inhibition induced by E2FBP1 depletion is also observed in human tumor cells with intact p16INK4A and Rb. These results suggest that E2FBP1 functions as a critical antagonist to the pI6INK4A-Rb tumor suppressor machinery by regulating PML stability.

Pathophysiology, clinical features and radiological findings of differentiation syndrome/all-trans-retinoic acid syndrome

In acute promyelocytic leukemia, differentiation thera-py based on all-trans-retinoic acid can be complicated by the development of a differentiation syndrome(DS). DS is a life-threatening complication, characterized by respiratory distress, unexplained fever, weight gain, interstitial lung infiltrates, pleural or pericardial effusions, hypotension and acute renal failure. The diagnosis of DS is made on clinical grounds and has proven to be difficult, because none of the symptoms is pathognomonic for the syndrome without any definitive diagnostic criteria. As DS can have subtle signs and symptoms at presentation but progress rapidly, end-stage DS clinical picture resembles the acute respiratory distress syndrome with extremely poor prognosis; so it is of absolute importance to be conscious of these complications and initiate therapy as soon as it was suspected. The radiologic appearance resembles the typical features of cardiogenic pulmonary edema. Diagnosis of DS remains a great skill for radiologists and haematologist but it is of an utmost importance the cooperation in suspect DS, detect the early signs of DS, examine the patients' behaviour and rapidly detect the complications.

Onco-microRNA miR-130b promoting cell growth in children APL by targeting PTEN

Objective:To study the expression of microRNA-130b(miR-l 30b) in children acute promyelocytic leukemia(APL) and its role for regulating PTEN expression.Methods:A total of SO children APL marrow tissues and IS normal marrow tissues between January and December in 2012 were collected into our study.The expression of miR-l30 b in APL and normal marrow tissues were detected by quantitative real-time polymerase chain reaction.MiR-l30 b inhibitor was transfected into HL-60 cells.Cell Counting Kit-8 assay and flow cytometry were used to measure cell proliferation and apoptosis.respectively.The expression of PTEN,a potential target of miR-130 b,and its downstream genes,Bcl-2 and Box,in transformed cells were detected by quantitative real-time polymerase chain reaction and western-blot Results:The expression of miR-l30 b was significantly higher in children APL marrow tissues than in normal marrow tissues(P<0.05).Down-regulation of miR-1 30 b could significantly suppress cell proliferation and induce apoptosis in HL-60 cells(P<0.05).PTEN expression was upregulated when miR-130 b was knocking-down(P<0.05).As downstream genes of PTEN,the expression of Bcl-2 and Box were regulated as well.Conclusions:MiR-130 b is overexpressed in children APL marrow tissues and associated with cell growth.MiR-130 b may promote children APL progression by inducing cell proliferation and inhibiting apoptosis.

Secondary acute promyelocytic leukemia following chemotherapy for gastric cancer: A case report

Therapy-related acute myeloid leukemia(t-AML) refers to a heterogeneous group of myeloid neoplasms that develop in patients following extensive exposure to either cytotoxic agents or radiation.The development of t-AML has been reported following treatment of cancers ranging from hematological malignancies to solid tumors; however, to our knowledge, t-AML has never been reported following treatment of gastric cancer.In this study, we report the development of t-acute promyelocytic leukemia in a cT 4N1M0 gastric cancer patient after an approximate 44 mo latency period following treatment with 4 cycles of oxaliplatin(OXP)(85 mg/m2 on day 1) plus capecitabine(1250 mg/m2 orally twice daily on days 1-14) in combination with recombinant human granulocyte-colony stimulating factor treatment.Karyotype analysis of the patient revealed 46,XY,t(15;17)(q22;q21)[15]/46,idem,-9,+add(9)(p22)[2]/46,XY[3], which, according to previous studies, includes some "favorable" genetic abnormalities.The patient was then treated with all-trans retinoic acid(ATRA, 25 mg/m2/d) plus arsenic trioxide(ATO, 10 mg/d) and attained complete remission.Our case illuminated the role of certain cytotoxic agents in the induction of t-AML following gastric cancer treatment.We recommend instituting a mandatory additional evaluation for patients undergoing these therapies in the future.

Nuclear domain 10 of the viral aspect

Nuclear domain 10(ND10) are spherical bodies distributed throughout the nucleoplasm and measuring around 0.2-1.0 μm. First observed under an electron microscope, they were originally described as dense bodies found in the nucleus. They are known by a number of other names, including Promyelocytic Leukemia bodies(PML bodies), Kremer bodies, and PML oncogenic domains. ND10 are frequently associated with Cajal bodies and cleavage bodies. It has been suggested that they play a role in regulating gene transcription. ND10 were originally characterized using human autoantisera, which recognizes Speckled Protein of 100 kD a, from patients with primary biliary cirrhosis. At the immunohistochemical level, ND10 appear as nuclear punctate structures, with 10 indicating the approximate number of dots per nucleus observed. ND10 do not colocalize with kinetochores, centromeres, sites of mR NA processing, or chromosomes. Resistance of ND10 antigens to nuclease digestion and salt extraction suggest that ND10 are associated with the nuclear matrix.They are often identified by immunofluorescent assay using specific antibodies against PML, Death domainassociated protein, nuclear dot protein(NDP55), and so on. The role of ND10 has long been the subject of investigation, with the specific connection of ND10 and viral infection having been a particular focus for almost 20 years. This review summarizes the relationship of ND10 and viral infection. Some future study directions are also discussed.

RELATIONSHIP BETWEEN G-CSF AND HYPERLEUKOCYTOSIS INPATIENTS WITH APL AFTER TREATMENT WITH ALL-TRANSRETINOIC ACID

Objective: To detect the G-CSF effect and its mechanism in hyperleucocytosis of patients with APL after treatment with all-trans retinoic acid (ATRA). Methods: MTT method was used to measure the proliferation of HL-60 cells or primary APL cells. cDNA-mRNA dot blot hybridization was used to detect the c-myc gene expression level of HL-60 cells after ATRA treatment. Cycle shift of HL-60 cells was measured by flow cytometric Analysis. Results: ATRA could inhibit obviously in vitro the proliferation of HL-60 cells of primary APL cells. The G0/G1 ratio of HL-60 at 24 hours or 96 hours post-treatment with ATRA was increased, proliferation of HL-60 cells at the same time was promoted obviously under the condition of rhG-CSF. C-myc gene expression was analyzed by dot blot hybridization; its expression levels of 8, 24 or 96 hours in culture with ATRA separately were higher, low, high or lower as compared with each other. Conclusion: G-CSF plays an important role in hyperleucocytosis of patients with APL after treatment with ATRA.

All-trans Retinoic Acid,Arsenic Trioxide,and Anthracycline-based Chemotherapy Improves Outcome in Newly Diagnosed Acute Promyelocytic Leukemia Regardless of FLT3-ITD Mutation Status

All-trans retinoic acid(ATRA)and pre-upfront arsenic trioxide(ATO)have revolutionized the therapy of acute promyelocytic leukemia(APL).However,internal tandem duplication of FMS-like tyrosine kinase 3(FLT3-ITD)mutations is associated with increased risk of relapse.The aim of this study was to analyze the prognostic impact of FLT3-ITD on APL patients who received remission induction with ATRA,idarubicin(IDA)and/or ATO,followed by ATRA plus ATO along with anthracycline,as consolidation therapy.A total of 72 patients newly diagnosed with APL were included in this study.83.3%of the patients achieved complete remission(CR)after induction therapy.FLT3-ITD mutations were detected in 16(22.2%)patients and closely related to bcr-3 PML-RARa transcript(P<0.001).The 5-year overall survival(OS)rate was 100%in both FLT3-ITDposltlve and FLT3-ITD^(negatlve)groups,and there was no significant difference in 5-year event-free survival(EFS)between the two groups(78.3%vs.83.3%,P=0.85).ATRA plus ATO and anthracycline-based chemotherapy achieved great outcome in newly diagnosed APL regardless of the FLT3-ITD mutation status.

Hepatitis C-associated liver carcinogenesis:Role of PML nuclear bodies

Successful escape from immune response characterises chronic hepatitis C virus(HCV) infection,which results in persistence of infection in about 80% of the patients.The deleterious consequences are cirrhosis and hepatocellular carcinoma.HCV accounts the most frequent cause for hepatocellular carcinoma(HCC) and liver transplantation(LT) in the western world.The underlying molecular mechanisms how HCV promotes tumor development are largely unknown.There is some in vitro and in vivo evidence that HCV interferes with the tumor suppressor PML and may thereby importantly contribute to the HCV-associated pathogenesis with respect to the development of HCC.The tumor suppressor protein "promyelocytic leukemia"(PML) has been implicated in the regulation of important cellular processes like differentiation and apoptosis.In cancer biology,PML and its associated nuclear bodies(NBs) have initially attracted intense interest due to its role in the pathogenesis of acute promyelocytic leukemia(APL).More recently,loss of PML has been implicated in human cancers of various histologic origins.Moreover,number and intensity of PML-NBs increase in response to interferons(IFNs) and there is evidence that PML-NBs may represent preferential targets in viral infections.Thus,PML could not only play a role in the mechanisms of the antiviral action of IFNs but may also be involved in a direct oncogenic effect of the HCV on hepatocytes.This review aims to summarise current knowledge about HCV-related liver carcinogenesis and to discuss a potential role of the nuclear body protein PML for this this hard-to-treat cancer.

Sweet syndrome and differentiation syndrome in a patient with acute promyelocytic leukemia

The differentiation syndrome is an inflammatory reaction with increased capillary permeability that occurs in up to 25% of patients with acute promyelocytic leukemia treated with all-trans retinoic acid. A 50-year-old man with acute promyelocytic leukemia underwent chemotherapy with idarubicin and all-trans retinoic acid. On day +21 the patient developed pruritic prepatelar papules as well as several 10 mm subcutaneous nodules in both thighs accompanied by persistent fever. On the day +25 the patient presented with bilateral pulmonary crackles, infiltrates in the right lower lobe and severe hypotension which required dopamine infusion. Biopsy of one of the thighs nodules was performed. A Sweet syndrome associated to a differentiation syndrome was suspected. All-trans retinoic acid therapy was discontinued and dexamethasone was administered. In 48 h the patient showed remission of the fever and the infiltrates and the skin lesions acquired a residual aspect. It is debatable whether these two syndromes are distinct entities with common mechanisms or whether they are poles of the same spectrum. Dermatologists and hematologists must be aware of these two syndromes and its pathophysiologic association.

Successful treatment of relapsed acute promyelocytic leukemia with arsenic trioxide in a hemodialysis-dependent patient: A case report

BACKGROUND Arsenic trioxide(ATO)is recommended for patients who do not achieve molecular remission or who have molecular or morphologic relapse.However,there are no guidelines for adjusting ATO dosage in patients with severe renal failure or on dialysis.Herein,we report the successful treatment of relapsed acute promyelocytic leukemia(APL)in a patient on hemodialysis with ATO single agent and review the cases in literature.CASE SUMMARY A 46-year-old woman who has been on hemodialysis to chronic glomerulonephritis for 15 years visited our hospital for pancytopenia.She had been seen for pancytopenia 3 years ago and had been diagnosed with APL.She also received chemotherapy for APL but unfortunately was lost to follow-up after her second consolidation chemotherapy.She was noted to have pancytopenia by her nephrologist during hemodialysis 1 mo ago.Bone marrow biopsy and reverse transcriptase-polymerase chain reaction(RT-PCR)tests revealed a diagnosis of relapsed APL.Treatment for relapsed APL with ATO single agent was started and she achieved molecular remission after administering 24 doses of ATO.Thus far,four consolidation therapies have been performed with the ATO single agent,and,to date,the molecular remission has been maintained as negative promyelocytic leukemia/retinoic acid receptor-αfusion gene as confirmed by RTPCR testing for two years.CONCLUSION This is a rare case of relapsed APL successfully treated with the single agent ATO in a patient on hemodialysis.

Myeloid sarcoma of the colon as initial presentation in acute promyelocytic leukemia:A case report and review of the literature

BACKGROUND Myeloid sarcoma(MS)rarely occurs in acute promyelocytic leukemia(APL)at onset,but it can develop in relapse cases,especially after APL treated with alltrans retinoic acid(ATRA).Therefore little is known about the clinical features and suitable treatment for APL related MS due to the rarity of the disease,although this may be different from the treatment and prognosis of MS in the relapse stage.To our best knowledge,this is the second case report of APL initial presentation as colon MS.CASE SUMMARY A 77-year-old woman complained of intermittent right lower abdominal pain,black stool,and difficult defecation for 2 mo.Physical examination showed diffuse tenderness during deep palpation and an anemic appearance.Laboratory findings showed positivity for fecal occult blood testing;white blood cell count:3.84×109/L;hemoglobin:105 g/L;platelet count:174×109/L;and negativity for tumor markers.Abdominal enhanced computed tomography showed a space occupying lesion in the colon(1.9 cm).Fibrocolonoscopy revealed a polypoid and ulcerated mass measuring 2.5 cm.The tumor was removed.To our surprise,MS was confirmed by immunohistochemistry.PML/RARαfusion gene was detected in colon specimens by fluorescent in situ hybridization and real-time reverse transcription polymerase chain reaction,which was consistent with the bone marrow.She was diagnosed as having APL related MS.A smooth and unobstructed intestinal wall was found by fibrocolonoscopy,and continuous molecular remission was confirmed in both the bone marrow and colon after four courses of ATRA+arsenic trioxide(ATO).ATRA+ATO showed a favorable therapeutic response for both APL and MS.CONCLUSION Early use of ATRA can benefit APL patients,regardless of whether MS is the first or recurrent manifestation.

Gemtuzumab ozogamicin in the treatment of adult acute myeloid leukemia

Gemtuzumab ozogamicin (GO) is a humanized anti-CD33 monoclonal antibody conjugated to a derivative of an antitumor antibiotic, calicheamicin. GO was approved for the treatment of relapsed acute myeloid leukemia (AML) in the United States (US) in 2000. However, GO was withdrawn from the US market in June 2010, because a large-scale clinical trial failed to show additive or synergistic effects with conventional chemotherapy for newly diagnosed AML. GO is currently available only in Japan. However, several large clinical studies have demonstrated beneficial effects of GO when added to chemotherapy for AML in recent years;therefore, reconsideration of GO availability is gaining attention. Therefore, the role and efficacy of GO as monotherapy or in combination therapy for de novo or relapsed AML should be positively investigated.

Relationship between hydrogen sulfide and inflammation in patients with acute promyelocytic leukemia complicated with infection

Objective:To investigate the clinical effect of hydrogen sulfide on acute promyelocytic leukemia (acute promyelocytic leukemia APL) complicated with infection.Methods: A total of 30 cases patients of APL complicated with infection were selected as experimental group, 26 cases patients with only APL as control group. Detect the H2S, C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-10 (IL-10) level in the blood of the experimental group and control group, comparing the above indicators have no significant difference between the two groups.Results: Experimental group of blood H2S, CRP, TNF-α and IL-1β levels were significantly increased, IL-10 decreased, which was statistically significant compared with the control group;the H2S, CRP, TNF-αand IL-1βlevels of the experimental group after the treatment were significantly decreased, IL-10 level increased, There was statistical significance compared with the experimental group before the treatment;compared with the control group, the difference was not statistically significant. The experimental group H2S was positively correlated with CRP, TNF-α and IL-1β, H2S was negatively correlated with IL-10.Conclusions: Endogenous H2S is involved in the pathophysiological process of inflammation in APL with infection, and its role may be similar to that of CRP, TNF-α and IL-1β, which is contrary to the effect of IL-10.

Antimicrobial activity against periodontopathogenic bacteria,antioxidant and cytotoxic effects of various extracts from endemic Thermopsis turcica

Objective:To investigate the in vitro antimicrobial potential of Thermopsis turcica Kit Tan,Vural&Kckdk against periodoutopathogenie bacteria,its antioxidant activity and cytotoxic effect on various cancer cell lines.Methods:In vitro antimicrobial activities of elhanol.methanol,ethyl acetate(ElAc,n-hexane and water extracts of Thermopsis turcica herb against periodontopathogenic bacteria,Aggregatibacter actinnmycelemconilans ATCC 29523 and Porphyromonas gingivalis ATCC 33277 were tested by agar well diffusion,minimum inhibitory concentration(MIC)and minimal bactericidal concentration(MBC),Antioxidant properties of the extracts were evaluatod by 1,1-diphenyl-2-picryl-hydrazyl radical scavenging activity and p-carotene bleaching methods.Amounts of phenolic contents of the extracts were also analysed by using the Folin-Ciocalteu reagent.Additionally,cytotoxic activity of the extracts on androgcn-insensilivc prostate cancer,androgen—sensitive prostate cancer,chronic myelogenous leukemia and acute promyelocytic leukemia bunian cancer cell lines were determined by 3-4,5-dimelhylthiazol-2-yh-2,5-diphenyltclrazolium bromide assay.Human gingival fibroblast cells were used as a control.Results:Our data showed that ELAc extract had the highest antimicrobial effect on Aggregatibacter actinomycetemitans(MIC:1.562 mg/ml_MHC:3.124 mg/ml.)and Porph yromonas gingiralis(MIC:0.781 mg/mL,MBC:1.562 mg/mL).In antioxidant assays.ElAc extract exhibited also the highest radical scavenging activity[IC_(50)=(30.0±0.3)μg/ml.]and the highest inhibition[(74.35±0.30)%]|against lineloic acide oxidation.The amount of phenolic content of it was also the highest[(l62.5±l.2)μg/mg gallic acid].In cytotoxic assay,only etbanol[IC_(50)=(80.00±1.21)μg/ml.]and EtAc extract[IC_(50)=(70.0±0.9)μg/ml]were toxic on acute promyeloeytic leukemia cells at 20—100μg/mL.P<0.05>.However,no toxic effect was observed on human gingival fibroblast cells.Cunclusions:According to our findings,owing to its antioxidant and cytotoxic potential,EtAc exlrael might include anticancer agents for acute promyelocytic leukemia.

Status epilepticus and acute promyelocytic leukemia

Neurological manifestations are rare as initial presentation in acute promyelocytic leukemia (APL). This case illustrates status epilepticus as initial presentation in this disease. Atypical cells on peripheral smear led to the diagnosis of leukemia.