Increased Lactate Dehydrogenase Levels Research Articles

Apolipoprotein E 4 triggers multiple pathway-mediated Ca2+ overload, causes CaMK II phosphorylation abnormity and aggravates oxidative stress caused cerebral cortical neuron damage.

Apolipoprotein E (APOE) gene polymorphism is correlated closely with resistance to brain damage. This study aims to investigate the effects of APOE4 on oxidative stress damaged cerebral cortical neuron. Primary cerebral cortical neurons were isolated from APOE gene knock-out mice (APOE-/- mice). Oxidative stress damaged APOE-/- mouse cerebral cortical neuron model was established. Three experimental designs (experiment 1, 2, 3) were conducted by employing several methods. Lactate dehydrogenase (LDH) and superoxide dismutase (SOD) analysis were employed for neurotoxicity assessment. Flow cytometry and transferase-mediated deoxyuridine-triphosphate-biotin nick end labeling (TUNEL) were used to examine neuron apoptosis. Immunohistochemistry and Nissl staining were used to identify neuron morphology. Western blot was used to detect phosphorylated CaMK II (p-CaMK II) and cleaved caspase 3 expression. Ca2+ levels in neurons were also examined by detecting fluorescence intensity. APOE4 treatment (Vehicle + APOE4) significantly aggravates oxidative stress damaged cerebral cortical neuron by increasing LDH levels and decreasing SOD activities, induces neuron apoptosis compared to Vehicle group (p < 0.05). APOE4 treatment significantly enhanced Ca2+ levels compared to Sham group (p < 0.05), MK801 treatment (Vehicle + APOE4 + MK801) significantly decreased Ca2+ levels compared to the Vehicle+APOE4 group at 12 h and 24 h (p < 0.05). APOE4 triggers CaMK II phosphorylation, caspase 3 activation and neurons apoptosis. Both of MK801 and KN93 inhibit CaMK II phosphorylation, decreases caspase 3 activation, and suppresses neurons apoptosis CONCLUSIONS: APOE triggers Ca2+ overload through NMDAR and CaMK II signaling pathway, both of which cause Ca2+ concentration increasing, CaMK II phosphorylation abnormity, and finally aggravate oxidative stress damaged neurons apoptosis.

Cytoprotective effects of glycyrrhetinic acid liposome against cyclophosphamide-induced cystitis through inhibiting inflammatory stress

This study was designed to investigate the pharmacological efficacy of glycyrrhetinic acid liposome (GAL) against female mice with nonbacterial cystitis induced by cyclophosphamide (CPS). Mice in different groups were subjected to tests for lactate dehydrogenase (LD), cytokine contents (IL-6, TNF-α) in serum, and histological changes in bladder tissue and to immunoassays. As a result, cyclophosphamide-induced cystitis in mice showed an increased LD level in serum, and the contents of cytokines (IL-6, TNF-α) were elevated. Interestingly, GAL-treated mice showed decreased LD and inflammatory cytokines of IL-6 and TNF-α in blood. Inflammatory infiltration and cell death in bladder tissue were reduced by GAL treatments. In addition, intravesical mRNAs of NF-κB and TNF-α were lowered dose-dependently in GAL-treated mice. As shown in cytohistological staining, the number of intravesical caspase-3, PARP-positive cells decreased in GAL-treated mice. Furthermore, a GAL-treated bladder showed down-regulated NF-κB and TNF-α expressions in a dose-dependent manner. In conclusion, our current findings may be the first to provide scientific evidence demonstrating that glycyrrhetinic acid liposomes provide benefits against cyclophosphamide-induced cystitis, which possibly occurs through underlying mechanisms that inhibit cell death and inflammatory stress.

Prognostic significance of a comprehensive histological evaluation of reticulin fibrosis, collagen deposition and osteosclerosis in primary myelofibrosis patients.

To evaluate whether a comprehensive histological evaluation of reticulin fibrosis, collagen deposition and osteosclerosis in bone marrow trephine biopsies (BMBs) of primary myelofibrosis (PMF) patients may have prognostic implications. Reticulin fibrosis, collagen deposition and osteosclerosis were graded from 0 to 3 in a series of 122 baseline BMBs. Then, we assigned to each case a comprehensive score [reticulin, collagen, osteosclerosis (RCO) score, ranging from 0 to 9] that allowed us to distinguish two groups of patients, with low-grade (RCO score 0-4) and high-grade (RCO score 5-9) stromal changes. Of 122 patients, 88 displayed a low-grade and 34 a high-grade RCO score. The latter was associated more frequently with anaemia, thrombocytopenia, peripheral blood blasts and increased lactate dehydrogenase levels. The RCO score was correlated strictly with overall mortality (P = 0.013) and International Prognostic Scoring System (IPSS) risk categories, and was able to discriminate the overall survival of both low- and high-grade patients (log-rank test: P < 0.001). Moreover, it proved to be more accurate than the European Consensus on Grading of Bone Marrow Fibrosis (ECGMF grade) in identifying high-risk patients with poor prognosis. Finally, a combined analysis of RCO scores and IPSS risk categories in an integrated clinical-pathological evaluation was able to increase the positive predictive value (PPV) for mortality in high-risk patients. The comprehensive RCO score, obtained by histological evaluation of reticulin fibrosis, collagen deposition and osteosclerosis was prognostically significant and more accurate than ECGMF grade in identifying high-risk patients and improved PPV when applied in addition to IPSS.

The role of frontline autologous stem cell transplantation for primary plasma cell leukemia: a retrospective multicenter study (KMM160).

Primary plasma cell leukemia (pPCL) is a rare and aggressive plasma cell neoplasm, with rapidly progressing clinical course. We evaluated the treatment status and survival outcomes of 69 Korean patients with pPCL. Of them, 59 patients were treated; 15 (25.4%) were treated initially with novel agent-based regimens with upfront autologous stem cell transplantation (ASCT), 7 (11.9%) with conventional chemotherapy with upfront ASCT, 21 (35.6%) with novel agent-based regimens only, and 16 (27.1%) were treated with conventional chemotherapy alone. Overall response rates after initial therapy were significantly higher in patients treated with novel agent-based regimens compared with those treated with conventional chemotherapies (75% vs. 43.4%, P = 0.026). Median progression-free survival (PFS) and overall survival (OS) were 12.2 months and 16.1 months, respectively. The median PFS of the four treatment groups–conventional chemotherapy alone, novel agents alone, conventional chemotherapy with ASCT, and novel agents with ASCT–were 1.2, 9.0, 10.5, and 26.4 months, respectively (P < 0.001); the median OS of the four treatment groups were 2.9, 12.3, 14.1, and 31.1 months, respectively (P < 0.001). The median OS was also significantly better in the patients with novel agents with ASCT versus other patients. In a multivariate analysis, an increased lactate dehydrogenase level, low albumin (< 3.5 g/dL), and non-CR after front-line treatment were independently associated with poor PFS and OS. In conclusion, the use of novel agent-based therapy with ASCT and achieving a deep response to front-line treatment are important in expecting improved PFS and OS in patients with pPCL.

The cardiotoxicity of crude tentacle-only extract from the Persian Gulf jellyfish “Cassiopea sp.” in isolated rat heart

The upside-down jellyfish produces venom with some biological activities. In the present study, direct cardiotoxicity of crude tentacle-only extract from the Persian Gulf jellyfish “Cassiopea sp.” was assessed by a Langendorff isolated perfused rat heart system. Treatments were performed with concentrations of 50, 20, 10, 5, and 2.5μg/ml of crude tentacle-only extract (CTOE) on isolated rat hearts for 60min. Then, the hemodynamic parameters of heart rate, left ventricular end-diastolic pressure, left ventricular systolic pressure, left ventricular developed pressure, and coronary flow were evaluated. Lactate dehydrogenase (LDH) levels as well as histopathological examinations were also investigated. Based on the ECG findings, treatments in a dose-dependent pattern changed cardiac electrical activity and decreased coronary effluent. The higher concentrations of CTOE produced severe bradycardia, atrioventricular dissociation, complete atrioventricular block, and ultimately cardiac arrest. Ventricular end-diastolic pressure was also significantly increased by high concentrations of CTOE. At high CTOE concentrations, scatter lymphocytic infiltration and wavy fibers were found in the histopathological examinations. Treatment with concentrations of 2.5–10μg/ml caused a considerable increase in LDH levels within 30min compared with baseline levels. In conclusion, CTOE from the Persian Gulf upside-down jellyfish had significant direct cardiotoxicity effects on isolated rat hearts.

Pneumocystis jiroveci pneumonia (PJP) in non-HIV immunocompromised individuals

Objectives: PJP is a major cause of morbidity and mortality in immunocompromised individuals. Diagnosing PJP is often difficult because respiratory signs might be minimal or absent and the sensitivity of a chest X-ray (CXR) is low. We studied the clinical risk factors in order to increase awareness and facilitate the diagnosis.Methods: We studied a prospective case series over a one year period (from 1 January 2015 to 1 January 2016) and did a retrospective analysis (from 2013 to 2016) of all PJP positive bronchoalveolar lavage (BAL) analysis.Results: Seven patients with metastatic solid tumors were diagnosed with symptomatic PJP (based on positive polymerase chain reaction) over a one year period. The median age was 61 years. Three patients had brain metastasis. Four of them were on steroids, the median dose was 16 mg methylprednisolone with three of them at a tapered dose. Respiratory failure developed in four cases and prompted intensive care monitoring. Two patients needed non-invasive ventilation and the third patient was intubated and mechanically ventilated. No patient died of PJP. A retrospective analysis on microbiological results obtained from BAL in our hospital from 2013 to 2016 shows a striking high percentage PJP positivity in cancer patients (including hematologic cancers) of nearly 22% (15/69) as opposed to the overall number of PJP-positives 7.3% (59/803).Discussion: The incidence of clinical PJP in patients treated for metastatic cancer is substantial. A high index of suspicion, especially in cases with unexplained respiratory symptoms, concurrent or recent use of steroids, a normal CXR and otherwise unexplained increased lactate dehydrogenase levels, is critical. The threshold for performing a CT-scan must be low and the diagnosis needs to be confirmed microbiologically.

Pterostilbene attenuates high glucose-induced oxidative injury in hippocampal neuronal cells by activating nuclear factor erythroid 2-related factor 2

In the present study, neuroblastoma (SH-SY5Y) cells were used to investigate the mechanisms mediating the potential protective effects of pterostilbene (PTE) against mitochondrial metabolic impairment and oxidative stress induced by hyperglycemia for mimicking the diabetic encephalopathy. High glucose medium (100mM) decreased cellular viability after 24h incubation which was evidenced by: (i) reduced mitochondrial complex I and III activities; (ii) reduced mitochondrial cytochrome C; (iii) increased reactive oxygen species (ROS) generation; (iv) decreased mitochondrial membrane potential (ΔΨm); and (v) increased lactate dehydrogenase (LDH) levels. PTE (2.5, 5, and 10μM for 24h) was nontoxic and induced the nuclear transition of Nrf2. Pretreatment of PTE (2.5, 5, and 10μM for 2h) displayed a dose-dependently neuroprotective effect, as indicated by significantly prevented high glucose-induced loss of cellular viability, generation of ROS, reduced mitochondrial complex I and III activities, reduced mitochondrial cytochrome C, decreased ΔΨm, and increased LDH levels. Moreover, the levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and glutathione S-transferase (GST) were elevated after PTE treatment. In addition, the elevation of nuclear Nrf2 by PTE treatment (10μM for 2h) was abolished by Nrf2 siRNA. Importantly, Nrf2 siRNA induced the opposite changes in mitochondrial complex I and III activities, mitochondrial cytochrome C, reactive species generation, ΔΨm, and LDH. Overall, the present findings were the first to show that pterostilbene attenuated high glucose-induced central nervous system injury in vitro through the activation of Nrf2 signaling, displaying protective effects against mitochondrial dysfunction-derived oxidative stress.

Iron oxide nanoparticles modulate heat shock proteins and organ specific markers expression in mice male accessory organs

With increased industrial utilization of iron oxide nanoparticles (Fe2O3-NPs), concerns on adverse reproductive health effects following exposure have been immensely raised. In the present study, the effects of Fe2O3-NPs exposure in the seminal vesicle and prostate gland were studied in mice. Mice were exposed to two different doses (25 and 50 mg/kg) of Fe2O3-NPs along with the control and analyzed the expressions of heat shock proteins (HSP60, HSP70 and HSP90) and organ specific markers (Caltrin, PSP94, and SSLP1). Fe2O3-NPs decreased food consumption, water intake, and organo-somatic index in mice with elevated iron levels in serum, urine, fecal matter, seminal vesicle and prostate gland. FTIR spectra revealed alterations in the functional groups of biomolecules on Fe2O3-NPs treatment. These changes are accompanied by increased lactate dehydrogenase levels with decreased total protein and fructose levels. The investigation of oxidative stress biomarkers demonstrated a significant increase in reactive oxygen species, nitric oxide, lipid peroxidation, protein carbonyl content and glutathione peroxidase with a concomitant decrement in the glutathione and ascorbic acid in the male accessory organs which confirmed the induction of oxidative stress. An increase in NADPH-oxidase-4 with a decrease in glutathione-S-transferase was observed in the seminal vesicle and prostate gland of the treated groups. An alteration in HSP60, HSP70, HSP90, Caltrin, PSP94, and SSLP1 expression was also observed. Moreover, accumulation of Fe2O3-NPs brought pathological changes in the seminal vesicle and prostate gland of treated mice. These findings provide evidence that Fe2O3-NPs could be an environmental risk factor for reproductive disease.

The effect of topical treatments for CRS on the sinonasal epithelial barrier.

Several topical treatments are used in the management of Chronic Rhinosinusitis (CRS), some of which the safety and efficacy has yet to be determined. The purpose of this study was to investigate the effect of commonly used topical treatments on the sinonasal epithelial barrier. Normal saline (0.9% Sodium Chloride), hypertonic saline (3% Sodium Chloride), FESS Sinu-Cleanse Hypertonic, FLO Sinus Care and Budesonide 1 mg/ 2 ml were applied to the apical side of air-liquid interface (ALI) cultures of primary human nasal epithelial cells (HNECs) from CRS patients (n=3) and non-CRS controls (n=3) for 24 hours. Epithelial barrier structure and function was assessed using trans-epithelial electrical resistance (TEER), measuring the passage of Fluorescein Isothiocyanate labelled Dextrans (FITC-Dextrans) and assessing the expression of the tight junction protein Zona Occludens-1 (ZO-1) using immunofluorescence. Toxicity was assessed using a Lactate Dehydrogenase (LDH) assay. Data was analysed using ANOVA, followed by Tukey HSD post hoc test. Hypertonic solution and budesonide significantly increased TEER values in CRS derived HNECs. In contrast, FESS Sinu-Cleanse Hypertonic significantly reduced TEER 5 minutes after application of the solution followed by an increase in paracellular permeability of FITC-Dextrans (30 minutes) and increased LDH levels 6 hours after application of the solution. Our findings confirm that isotonic and hypertonic saline solutions do not compromise epithelial barrier function in vitro but underscore the importance of examining safety and efficacy of over-the-counter wash solutions.

Clinical Status of Lactate Dehydrogenase Activity in Cerebrospinal Fluid with Age and Sex Distribution in Different Types of Meningitis

Aim: The cerebrospinal fluid concentrations of Lactate dehydrogenase (LDH) were studied in patients with pyogenic, tubercular and viral meningitis in different age and sex group. Material and methods: A total of 160 cases, aged between 1 month and 60 years, including patients with bacterial meningitis (n=50), pyogenic meningitis (n=46), viral meningitis (n=24) and a control group (n=40), were analyzed on the basis of data from the initial clinical examinations. Results:Significant increase in LDH level (P<0.001) were observed in the test group when compared to the control group. Bacterial meningitis is more common than non bacterial meningitis. Pyogenic meningitis is more prevalent under 1 year of age group while tuberculous meningitis is seen most frequently betweens 3 to 5 year of age. Conclusion:The maximum prevalence of different types of meningitis was in the age group of 1 to 10 years age. The LDH level did rise quite significantly in pyogenic meningitis.

TESTICULO-PROTECTIVE EFFECT OF MORINGAOLEIFERA SEED EXTRACT ON COPPER SULPHATE INDUCED INJURY IN WISTAR RATS

The aim of this study was to observe the testiculo-protective effect of aqueous extract of Moringaoleifera seed also known as Moringa seed on copper sulphate induced injury in Wistar rats. Twenty adult male Wistar rats (200-300g) were randomly selected into four groups (5 rats per group). Group A served as control group and were given 2ml/kg of distilled water. Group B was administered aqueous extract of Moringa seed only (200mg/kg body weight). Group C was administered aqueous extract of Moringa seed (200mg/kg body weight) and copper sulphate (100mg/kg body weight) concurrently. Group D was administered copper sulphate only (100mg/ kg body weight). All administrations lasted for three weeks. Results showed that in group D, there was proliferation of interstitial cells, degeneration of the seminiferous tubules as evidenced by hyalinization and blockage of the tubular lumen by immature spermatogenic series due to an arrest of spermatogenesis. There was also a significant decrease in testosterone level anda significant increase in lactate dehydrogenase level when compared with the control at p< 0.05. In group C rats, the results show mild interstitial connective tissue loosening and normal sequential maturation of spermatogenic series and normal levels of testosterone and lactate dehydrogenase. Conclusively, administration of copper sulphate causes testicular damage as evidenced by testicular hyalinization and arrest of spermatogenesis. However concurrent treatment of the rats with Moringa oleifera seed extract and copper sulphate have no effect on the testes, establishing the fact that Moringa oleifera seed extract offers a protective effect to the testes. Keywords: Testosterone; Moringa; copper sulphate; wistar rat; Moringa oleifera

Use of LDH and autoimmune side effects to predict response to ipilimumab treatment.

Ipilimumab is a cytotoxic T-lymphocyte antigen-4 antibody that enhances T-cell activity and proliferation. In a retrospective analysis of 86 patients the clinical benefits of ipilimumab treatment were correlated with laboratory and clinical data. A lactate dehydrogenase (LDH) value within the normal range before the start of therapy was significantly correlated with better OS (p ≤ 0.009). An increase in LDH level after two cycles was indicative of a poor outcome, and was significantly negatively correlated with treatment response and overall survival and progression-free survival. 42% of all patients suffered from autoimmune toxicity (CTCAE grades 2-4). The occurrence of autoimmune toxicity clearly correlated with clinical benefit. Changes in LDH level and side effects correlate with response to therapy and survival.

Hemolysis after Oral Artemisinin Combination Therapy for Uncomplicated Plasmodium falciparum Malaria.

Episodes of delayed hemolysis 2-6 weeks after treatment of severe malaria with intravenous artesunate have been described. We performed a prospective observational study of patients with uncomplicated malaria to investigate whether posttreatment hemolysis also occurs after oral artemisinin-based combination therapy. Eight of 20 patients with uncomplicated malaria who were given oral artemisinin-based combination therapy met the definition of posttreatment hemolysis (low haptoglobin level and increased lactate dehydrogenase level on day 14). Five patients had hemolysis persisting for 1 month. Patients with posttreatment hemolysis had a median decrease in hemoglobin level of 1.3 g/dL (interquartile range 0.3-2.0 g/dL) in the posttreatment period, and patients without posttreatment hemolysis had a median increase of 0.3 g/dL (IQR -0.1 to 0.7 g/dL; p = 0.002). These findings indicate a need for increased vigilance for hemolytic events in malaria patients, particularly those with predisposing factors for anemia.

Retrospective Analysis of Prognostic Factors in 187 Cases of Transformed Mycosis Fungoides.

Large cell transformation (LCT) of mycosis fungoides (MF) is associated with an aggressive clinical course, poor overall survival (OS), and variable CD30 expression. We retrospectively analyzed 1900 MF/Sézary syndrome patients' clinical, histologic and immunophenotype and identified 187 patients seen between 1982 and 2012. Most advanced stage patients with LCT were male 86 of 155 (55.4%) and 69 were female (44.5%). Incidence of LCT (n = 187) was 9.8% (187/1900) in skin and/or nodes of the entire MF/SS database population (n = 1900). Advanced stage patients represented 83% of patients whose median OS was 4.1 years (95% confidence interval [CI], 3.5-5.4). Early stage patients represented 17% with OS of 8.0 years. Among 187 LCT patients, 136 patients (73%) were diagnosed with LCT at the time of initial diagnosis of MF. Their median OS was 3.6 years (95% CI, 3.3-5.3). Of the 51 patients who had LCT diagnosed after their initial diagnosis of MF, their median OS was 8.8 years (P = .0001; 95% CI, 1.6-4.1). The OS for all LCT patients was 4.8 years, for patients older than 60 years of age OS was 3.7 years (95% CI, 2.7-5.4) and was 6.2 years (95% CI, 4.5-9.8) for patients younger than 60 years of age (P = .0001). An increased lactate dehydrogenase level was associated with a decreased OS (P = .03; hazard ratio, 1.5; 95% CI, 1.0-2.2). Patients with CD30 expression in ≥ 10% of the lymphocytes in skin biopsies were 40% more likely to survive than patients with low expression. In summary, risk factors associated with disease progression were advanced age, LCT at the time of initial diagnosis of MF, high levels of lactate dehydrogenase, and CD30 expression < 10%.

유자 에탄올 추출물의 면역력 증진 효과

Citrus junos Sieb. ex Tanaka has been traditionally called Yuza in Korea and is used as a cuisine material or tea as well as medicinal herb. In this study, we evaluated the immune-enhancing effect of Citrus junos ethanol extract (CJE) on RAW264.7 mouse macrophage and primary immunocytes. CJE treatment showed increased macrophage activity in a dose-dependant manner. CJE also enhanced natural killer (NK) cell activity. We measured lactate dehydrogenase (LDH) level as a measurement of NK cell cytotoxicity against YAC-1 lymphoma cells. CJE treatment showed an increased LDH level in a dose-dependent manner. Finally, we evaluated the effect of CJE on mouse primary splenocyte proliferation. CJE treatment slightly increased splenocyte proliferation compared to the control. The results of this study suggest that CJE can help immune function via macrophage cytokine production, increased NK cell activity, and splenocyte proliferation.

AGPAT2 deficiency impairs adipogenic differentiation in primary cultured preadipocytes in a non-autophagy or apoptosis dependent mechanism

AimsMutations in 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2) result in lipodystrophy, insulin resistance and diabetes. Autophagy is required for normal adipogenesis and adipose tissue development. The aim of this study was to determine whether impaired autophagy or excessive cell death underlie the adipogenic inability of Agpat2−/− mice preadipocytes. MethodsPreadipocytes were isolated from interscapular brown adipose tissue (BAT) of Agpat2−/− and Agpat2+/+ newborn mice and cultured/differentiated in vitro. Intracellular lipids were quantified by oil red O staining. Cell death was assessed by lactate dehydrogenase (LDH) activity. Apoptosis and autophagy regulatory factors were determined at the mRNA and protein level with Real-time PCR, immunoblot and immunofluorescence. ResultsAdipogenically induced Agpat2−/− preadipocytes had fewer lipid-loaded cells and lower levels of adipocyte markers than wild type preadipocytes. Before adipogenic differentiation, autophagy-related proteins (ATGs) ATG3, ATG5–ATG12 complex, ATG7 and LC3II were increased but autophagic flux was reduced, as suggested by increased p62 levels, in Agpat2−/− preadipocytes. Adipogenic induction increased LDH levels in the culture media in Agpat2−/− preadipocytes but no differences were observed in the activation of Caspase 3 or in markers of autophagic flux. ConclusionsAGPAT2 is required for in vitro adipogenesis of mouse preadipocytes. Autophagy defects or apoptosis are not involved in the adipogenic failure of Agpat2−/− preadipocytes.

Value of radiotherapy for early-stage Waldeyer’s ring diffuse large B-cell lymphoma in the rituximab era

Objective To evaluate the value of radiotherapy following rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)-based chemotherapy for patients with early-stage Waldeyer’s ring diffuse large B-cell lymphoma (WR-DLBCL). Methods Eighty-three patients diagnosed with early-stage WR-DLBCL who were admitted to our hospital from 2000 to 2013 were enrolled in the study. In these patients, twenty-five had stage Ⅰ disease and fifty-eight had stage Ⅱ disease. All patients received R-CHOP-based chemotherapy with (n=62) or without (n=21) involved-field radiotherapy (Waldeyer’s ring plus cervical lymph nodes). The overall survival (OS), progression-free survival (PFS), and local-regional control (LRC) rates were calculated using the Kaplan-Meier method. The univariate analysis was performed using the log-rank method. The multivariate analysis was performed using the Cox regression model. Results In all patients, the 5-year sample size was 18; the 5-year OS, PFS, and LRC rates were 89%, 84%, and 90%, respectively. According to the univariate analysis, patient age greater than 60 years, an increased lactate dehydrogenase level, Eastern Cooperative Oncology Group (ECOG) performance status no less than 2, and International Prognostic Index (IPI) no less than 2 were poor prognostic factors. Patient age greater than 60 years, a tumor size no less than 5 cm, ECOG performance status no less than 2, and IPI no less than 2 were influencing factors for PFS and LRC rates. In addition to the treatment with rituximab, patients treated with consolidative radiotherapy had significantly higher PFS and LRC rates (94% vs. 58%, P=0.003; 100% vs. 61%, P=0.000) as well as slightly higher OS rate (94% vs. 71%, P=0.063) than those treated without radiotherapy. Conclusions Consolidative radiotherapy following R-CHOP-based chemotherapy significantly improves PFS, LRC, and probably OS rates for early-stage WR-DLBCL. This conclusion still needs to be confirmed by prospective studies with a large sample size. Key words: Waldeyer ring diffuse large B-cell lymphoma/radiotherapy; Waldeyer ring diffuse large B-cell lymphoma/chemotherapy; Rituximab

Treatment of children with highly suspected mature B-cell lymphoblastic leukemia

Objective To evaluate the outcomes of mature B-cell acute lymphoblastic leukemia(mature B-ALL)and to assess the safety and efficacy of the treatment protocol. Methods From February of 2003 to December of 2012, 15 children were diagnosed as mature B-cell acute lymphoblastic leukemia/lymphoma possible (mature B-ALL/NHLp) in Shanghai Children's Medical Center(SCMC) were enrolled, and they were treated with SCMC-mature B-ALL/NHLp-2003 protocol .All of the clinical characteristics, therapeutic effects and long-term outcomes were analyzed.The statistical data were processed by SPSS 21.0. Results The median age on diagnosis was 8.7 years (1 year and 5 months to 14 years and 4 months). Among them, 4 cases presented with local mass including maxillofacial tumors, neck and abdominal mass.The others had systemic manifestations such as fever and pale face. These neoplastic cells retained the expressions of surface membrane immunoglobulin M, terminal deoxynucleotidyl transferase, Cμ, CD10, CD19, cCD79a differently.Follow-up was updated to November 30, 2013.The median follow-up period was 80 months(39-128 months). Theestimated 5-year event free survival rate was (80.0±10.3)%.According to univariate analysis, increased lactate dehydrogenase level (> 4-times the normal value), increased serum ferritin level (> 2-times the normal value), no small residual disease markers were indepen-dent poor prognostic factors(χ2=5.49, 4.89, 5.49, all P<0.05). Conclusions SCMC-mature B-NHL/ALLp-2003 protocol is feasible and safe for children with mature B-ALL/NHLp, but more sample cases need to be investigated. Key words: Mature B-cell acute lymphoblastic leukemia/lymphoma; Child; Curative effect; Event-free survival

Abstract 299: In vitro compound screening identifies enhancers of adenoviral oncolysis with Delta24-RGD in patient-derived glioblastoma stem cells

Abstract The tumor targeted oncolytic adenovirus Delta24-RGD is currently under phase I/II investigation for the malignant brain tumor glioblastoma. Despite encouraging results, the efficacy of oncolytic virotherapy still requires improvements due to heterogeneous or poor responses. In this study, we performed a screen of 446 clinically applied drugs to identify those that enhance Delta24-RGD oncolysis in glioblastoma. Cell viability was determined five days post-infection in Delta24-RGD resistant patient-derived glioblastoma stem cell (GSCs) cultures. Potential ‘hits’ were tested for synergistic viral sensitization using the Chou-Talalay method. Effects on viral infection and replication were investigated using Ad-Luc-RGD and Delta24-RGD-GFP viruses, and apoptosis and necrosis were evaluated using caspase-3/7 and lactate dehydrogenase (LDH) assays. Selection based on the efficacy of combination treatment led to the identification of ten drugs as potential Delta24-RGD sensitizers from the initial screen. Further analysis of effects on viral replication, synergistic interactions and ability to penetrate the blood-brain barrier narrowed this down to four remaining compounds, fluphenazine, indirubin, lofepramine and ranolazine. These four agents increased caspase-3/7 activity and fluphenazine also increased LDH levels in combination with Delta24-RGD. Fluphenazine, indirubin, lofepramine and ranolazine sensitized 12/12, 11/12, 9/12 and 11/12 distinct GSC cultures to Delta24-RGD, respectively. In conclusion, a clinical compound screen on glioblastoma stem cells in combination with in vitro mechanistic studies, revealed four highly effective compounds that sensitize GSCs to Delta24-RGD oncolytic therapy. Citation Format: Lotte ME Berghauser Pont, Rutger Balvers, Jenneke Kloezeman, Michal O. Nowicki, Andreas Kremer, E. Antonio Chiocca, Sieger Leenstra, Clemens MF Dirven, Sean Lawler, Martine LM Lamfers. In vitro compound screening identifies enhancers of adenoviral oncolysis with Delta24-RGD in patient-derived glioblastoma stem cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 299. doi:10.1158/1538-7445.AM2015-299

Heart beats: not to be beaten.

Heart beats: not to be beaten.