bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune Suppression by Placenta Derived Adherent Cells (PDAC) Correlate with Monocyte Chemoattractant Protein-1 and IL-2 Secretion.
Authors: Paludan Casper , Harbacheuski Ryhor , Murray Rose Ann , Mendillo Megan , Soler Jorge , Wang Jia-Lun , Ye Qian , Edinger James , Hofgartner Wolfgang , Kaplan Gilla , Hariri Robert 
Published: October 2019

Abstract
The placenta is a readily available and ethically non-controversial source of large amounts of therapeutic stem cells. Placenta Derived Adherent Cells (PDACs) are isolated from the placenta by one of several methods including physical disruption of tissue from several different anatomical sites within the placenta that include the amniotic membrane, chorion, placental cotyledons, or any combination thereof. Flow cytometry analysis showed that PDACs isolated from certain sites exhibit defined phenotypes, including for example CD200+ CD105+ CD73+ CD34− CD45− at percentages ≥70% and constitutively secrete IL-6, IL-8, and Monocyte Chemoattractant Protein-1 (MCP-1). PDACs demonstrate in vitro pluripotency in the adipogenic, osteogenic, and chondrogenic lineages. Furthermore, PDACs suppress T cell proliferation in certain Mixed Leukocyte Reaction (MLR) and the autologous EBV regression assays. Because secreted factors can powerfully modify immune responses and influence therapeutic use of cells, we report on the cytokine secretion in certain PDAC MLR and regression assays.
Cytokines were measured on a Luminex system in supernatants from 6-day PDAC cultures, PDAC MLRs or PDAC regression assays. MLRs include PDACs, Dendritic Cells (DC)s, and T cells at DC/PDAC/T ratios 1/2/10. EBV regression assays included PDACs, EBV antigen-presenting cells (APC), and T cells at APC/PDAC/T ratios 1/2/10. Levels of IL-6 (11 ng/ml) and IL-8 (16 ng/ml) stayed constant in PDAC solo cultures, PDAC MLRs, and PDAC regression assays. MCP-1 concentration was 2 ng/ml in PDAC solo cultures, and non-suppressive control adherent cell MLRs and regression assays, but increased to 10 ng/ml in suppressed PDAC MLRs and PDAC regression assays. These values are consistent with reported MCP-1 serum levels.
Interleukin-2 (IL-2) is both a T cell survival factor and an obligate factor for CD4+CD25+ T regulatory cells. T regulatory cells are not required for PDAC T cell suppression, but IL-2 levels consistently increase when MLR suppression by PDACs occurs. The CD4 MLR supernatants contained 65 pg/ml IL-2, and the CD8 MLR contained 35 pg/ml IL-2. In the 85% and 75% suppressed CD4 and CD8 PDAC MLRs, the IL-2 levels rose 5-fold to 331 pg/ml (CD4) and 2-fold to 67 pg/ml(CD8).
These results indicate that IL-2 and MCP-1, traditionally known as stimulators of the immune response, may play a role in PDAC immune suppression. PDACs, which cause the secretion, may thus be useful therapeutic tools in the clinic.
The Study on Difference in Megakaryocyte Expansion between Cord Blood and Peripheral Blood.
Authors: Fang Jian-pei , Xia Ting , Chen Guo-hua , Wu Yan-fen , Xu Hong-gui , Wei Qing , Huang Shao-liang 
Published: October 2019

Abstract
Objective Currently, thrombocytopenia is typically observed in patients undergoing hematopioetic stem cell transplantation (HSCT), high-dose chemotherapy or irradiation. Severe thrombocytopenia can cause bowel hemorrhage and intracranial hemorrhage. To transfuse ex vivo-expanded Mk cells into patients can reinforce the ability of platelet formation and shorten the time of platelet recovery. So it is one of the effective approaches to protect the danger. To explore the differences in megakaryocyte (MK) expansion between CD34+ stem cells derived from cord blood (CB) and Peripheral Blood (PB) and to establish the most optimal culture system.
Methods Mononuclear cells were isolated by density gradient centrifugation over Ficoll. CD34+ cells were isolated by positive selection using an immunomagnetic separation system. selected CD34+ cells were seeded in Iscove’s modified Kulbecco’s medium (IMDM) supplemented with fetal calf serum (FCS) and all kinds of cytokines. After 15–17 days of culture, the cells were measured and determined the content of CD41+ cells by flow cytometry, and simultaneously measured the number of megakaryocyte colony-forming unit (CFU-MK).
Results After the definite days of culture, the cytokine combination of TPO+FL+IL-6+IL-3 is most suitable both for PB and CB to obtain high numbers of MK, and better than any other three groups(P<0.05). The fold-increase of CD41+ cells from CB on day 14 was 193.23±25.24 fold, and that from PB on day 10 was 131.23±18.26 fold respectively. With the time gone, the number of CD41+ cells both decreased.
Conclusion For PB and CB, the cytokine combination of TPO+FL+IL-6+IL-3 is most suitable to obtain high numbers of MK and is the best combination for MK ex vivo expansion. It is suggested that MKs from CB have higher proliferation potential than that from PB, and the optimal culture duration of MK from PB is shorter than that of MK from CB. The study explore the differences in MK expansion between CD34+ stem cells derived from CB and PB and establish experimental foundation for further application to pre-clinic and clinic.
Human Cytomegalovirus Can Induce Alteration of β-Actin mRNA and Microfilaments as Well as Induce Apoptosis in Mesenchymal Stem Cells.
Authors: Wei Guoqing , Lin Maofang , Cai Zhen , Huang He 
Published: October 2019

Abstract
Mesenchymal stem cells (MSCs) is a very important cell system in bone marrow stromal and human cytomegalovirus (CMV) infection is one of the most common complications following stem cells transplantation. Our studies were to investigate the cytoskeleton change as well as the apoptosis induction effects of CMV infection on MSCs. In our study, MSCs were infected by 100,10,1 TCID50 of CMV. After 48h of culture with DMEM supplemented with 10% (v/v) fetal calf serum, MSCs shapes were observed with microscope. CMV particles and ultra structure in the cells were detected with transmission electron microscope. RT-PCR assay was used to detect the mRNA expression of CMV immediate early (IE) gene,β-actin gene and GAPDH genes. Flow Cytometry was used to detect the apoptotic cells. After the infection of CMV, shape of MSCs changed, turning from thin shuttle shape to round and thick ball shape, even escaping from wall. Cell shape changed more dominantly as the CMV titer increased. With transmission electron microscope, CMV particles and typical cellular apoptotic character as well as the ruptured- Microfilaments could be seen in the cells infected by CMV. MSCs infected by CMV could express IE mRNA and the expression of β-actin mRNA decreased in a time- and titer- dependent manner compared with the uninfected cells whose expression of GAPDH mRNA did not change much. With Flow Cytometry, it was found there were more apoptotic and necrosis cells in the cells infected by CMV. These results indicate that CMV can not only infect MSCs and destroy the cytoskeleton in the cells but also can induce apoptosis of the cells, much more attention of CMV infection on MSCs should be paid after stem cells transplantation.
Positive Expression of MUC1 Gene Is a Poor Prognostic Factor in Acute Myelogenous Leukemia.
Authors: Huang Ren-wei , Li Guo-wei , Wang Dong-ning , Li Xu-dong , Lin Gui-zhen , Lin Dong-jun 
Published: October 2019

Abstract
Objective: To study the expression of MUC1 in acute leukemia and its clinical significance.
Methods: Expression of MUC1 mRNA was detected in 73 newly diagnosed and relapsed patients of acute leukemia by reverse transcriptase polymerase reaction(RT-PCR). The MUC1 positive PCR products were analyzed by digestion with pst I. With clinical observation, the relationship of expression of MUC1 gene and treatment results were done.
Results: The expression of MUC1 was positive in 36 of 73 AL patients (49.3%). The MUC1 expression rate was 39.1% in ALL and 52.2% in AML and they show no significance difference. MUC1 gene was undetectable in 23 healthy subjects. Nineteen of 21 (90.5%) MUC1-negative non-M3 acute leukemia patients got CR while 14 of 22 (63.6%) MUC1-positive non-M3 acute leukemia patients got CR which showed significance difference (p<0.05); Only 9 of 16 cases of MUC1-positive non-M3 AML patients got CR(56.3%), while 10 of 11 patients of MUC1-negative non-M3 AML got CR(90.9%). The expression of MUC1 could turn negative after CR. There was no mutation of MUC1 gene correlating with digested site of pst I.
Conclusion: MUC1 expression is observed in some acute leukemia patients. The positive expression of MUC1 is not different between AML and ALL. The AML patients whose MUC1 gene showed positive got lower CR rate. It indicates that the expression of MUC1 can be used as a poor prognostic factor in AML and a marker for detection of minimal residual disease in AL.
Upregulation of FZ5 Results in Abberant Expression of Beta-Catenin and LEF/TCF Complex in Acute Myeloid Leukemia.
Authors: Atalar Fatmahan , Hatirnaz Ozden , Erbilgin Yucel , Ozbek Ugur , Sayitoglu Muge 
Published: October 2019

Abstract
Wnt proteins form a family of secreted signalling proteins that play a key role in various developmental events such as cell differentiation, cell migration, cell polarity and cell proliferation. Activation of the Wnt/beta-catenin through canonical and non-canonical pathways has recently been shown to be crucial to the self-renewal of hematopoietic progenitors and stem cells. WNT proteins initiate the canonical (beta-catenin-regulated) signaling cascade by binding to seven-transmembrane spanning receptors of the Frizzled (FZ) family. WNT stimulation leads to beta-catenin accumulation, nuclear translocation and interaction with T-cell factor/lymphoid enhancer factor (TCF/LEF) to regulate genes important for embryonic development and proliferation. Also beta-catenin is thought to have a role in the self renewal potential of leukemic cells in AML. To determine the role of the WNT pathways in the development of acute myeloid leukaemia (AML), we studied seven WNT pathway genes (WNT10b, WNT5a, FZ5, Beta-catenin, APC, TCF1 and LEF1) in 34 AML patients by quantitative real-time PCR. Results were compared by peripheral blood samples from healthy donors by using Ct values. FZ5 gene expression showed 10 fold and LEF1gene expression showed 3 fold increase when compared to controls (p>0.01 and p=0.02 respectively). Beta-catenin was 5 fold higher in patients than normal peripheral blood samples. The WNT10b expression was slightly lower (1.5 fold) comparing to other genes. TCF1 expression level also seemed to be higher in AML patients (OR=4.2 95%CI=0.04–2.82, p=0.06). These results may represent that canonical WNT signaling takes place in AML development and provide the evidence for the involvement of FZ5 upregulation in the pathogenesis of AML through activation of the TCF/LEF mediated signaling.
LMP1, LMP2A and CD40 Are All Essential for EBV-Associated Lymphoma Cell Survival.
Authors: Guasparri Ilaria , Cesarman Ethel 
Published: October 2019

Abstract
LMP1, LMP2A and CD40 induce signals that lead to activation of the transcription factor NF-kB. Since inhibition of NF-kB leads to the apoptosis of EBV-infected lymphoblastoid
and lymphoma cell lines, we sought to determine whether elimination of one or more of these signals is sufficient to induce apoptosis of lymphoma cells expressing this proteins.
We developed and tested siRNA targeting LMP1 and LMP2A, which were transfected into two EBV positive (Type III)-lymphoma cell lines (IBL-1 and BCKN1) and two lymphoblastoid
cell lines (RPMI-8402 and LCL-9001). LMP1 or LMP2A suppression with siRNA resulted in inhibition of basal NF-kB by approximately 75% in the Type III cell
lines tested, indicating that a significant proportion of the constitutive NF-kB activity is being induced by both LMP1 and LMP2A. Simultaneous elimination of both LMP1 and
LMP2A showed no significant additive or synergistic effect. Elimination of LMP1 and or LMP2A was sufficient to induce apoptosis of EBV infected cells, as evaluated by flow
cytometry for Annexin V after suppression of these proteins. No effect was seen in LMP1 negative controls. Simultaneous suppression of both proteins resulted in similar levels of apoptosis, with no additive or synergistic effect. As EBV+ lymphoma cell lines express CD40, as well as CD154 (CD40 ligand) causing an autocrine loop, we hypothesized that inhibition of CD40 signaling may enhance the apoptotic effect induced by suppression of LMP1 and LMP2A. Treatment with blocking antibody to CD154 (CD40 ligand) in conjunction with LMP1 or LMP2A suppression increased apoptosis by approximately 20%. These data indicate that CD40, LMP-1 and LMP2A are critical for survival of EBV-infected lymphoma cells expressing these proteins. Thus CD40 represents a potential cellular target, and LMP1 and LMP2A may be useful viral targets for the treatment of EBV-associated lymphomas.
Decreased Expression of Telomere Length Regulating Factors TRF1, and Tankyrase 1 in Patients with Adult Acute Leukemia.
Authors: Qian Wenbin , Yang Xiudi , Xu Weilai 
Published: October 2019

Abstract
Telomeric repeat binding factor 1 (TRF1) and Tankyrase 1 (a human telomeric poly(ADP-ribose) polymerase) may play key roles in the maintenance of telomere function. TRF1 negatively regulates telomere elongation, while Tankyrase 1 acts as positive regulator of telomere length. In this study, we examined the expressions of TRF1 and Tankyrase 1 in 46 samples from patients with acute leukemia at diagnosis by quantitative reverse transcription real-time polymerase chain reaction and then analyzed the relation with the expression of protooncogene c-myc. TRF1 mRNAs were significantly down-regulated in patients with acute leukemia compared to controls. On the other hand, the mononuclear cells (MNCs) of patient with acute myelogenous leukemia (AML) expressed TRF1 at higher levels than that of patient with acute lymphoblastic leukemia (ALL) (p<0.01) or myelodysplastic syndrome (MDS). Compared to the patients with CD 34 negative AML, patients with CD34 positive AML expressed lower levels of TFR1 (p<0.01). The expression levels of Tankyrase 1 mRNA progressively decreased in patients with MDS, AML and ALL, although it was not significant. Moreover, there was a significantly correlation between the expression of TRF1 mRNA and Tankyrase 1 mRNA in AML cells (r = 0.394, p<0.01). Expression of c-myc mRNA was found gradually reduced in patients with AML, ALL and MDS. Otherwise, the expression level of TRF1 significantly correlated with those of c-myc in patients with AML(r=0.381, p=0.02) and CD34 positive AML (r=0.814, p<0.01). These results suggest that TRF1 gene expression in acute leukemia is down-regulation, and higher expression of TRF1 mRNA may be a reason for shorter telomere in some AML cells. There is dysfunction of TRF1 expression in the CD34 positive subset of AML. The patients with lower expression of TRF1 may have a poor prognostic.
Dynamic Regulation of Mis-Folded N-CoR by Aberrant Protease and Its Implication in UPR-Induced Apoptosis of APL Cells.
Authors: Khan Matiullah 
Published: October 2019

Abstract
We have recently reported that accumulation of mis-folded N-CoR as insoluble protein aggregates in APL cells induces Endoplasmic Reticulum (ER) stress and activates unfolded protein response (UPR). Although, accumulation of mis-folded proteins is known to trigger UPR-induced cytotoxic cell death in several neurodegenerative disorders, APL cells are notably resistant to UPR-induced apoptosis. The molecular basis for the paradoxical response of APL cells to UPR is not known. Here we report that a glyco-protease, selectively expressed in APL cells, regulates APL cells’ response to UPR-induced apoptosis through processing of mis-folded N-CoR protein. Results show that mis-folded N-CoR is cleaved selectively in APL cells, and cellular extracts of APL cells and human primary APL cells contain activity that cleaves N-CoR protein. Purification and spectrometric analysis of N-CoR cleaving activity from an APL cell line reveals that it is a glycoprotein endopeptidase known as OSGEP. Furthermore, the cleavage of N-CoR in APL cells could be blocked by the broad-spectrum protease inhibitor, AEBSF, and by RNAi-mediated down-regulation of OSGEP expression. AEBSF selectively inhibits growth and promotes apoptosis of APL cells, possibly through a mechanism involving AEBSF-induced accumulation of insoluble N-CoR protein and by triggering ER stress. Taken together, these finding suggest that selective induction of protease activity in APL cells may represent a novel cytoprotective component of UPR, which could be exploited by tumor cells to survive the toxic insult of mis-folded protein(s).
Predictive Factors of All Trans-Retinoic Acid (ATRA) Related Complications during Induction Course of Acute Promyelocytic Leukemia (APL).
Authors: Ramzi Jeddi , Karima Kacem , Hend Benneji , Samia Mnif , Raihane Belakhal , Lamia Aissaoui , Hela Benabid , Zaher Belhadjali , Balkis Meddeb 
Published: October 2019

Abstract
Background: The combination of ATRA and chemotherapy has made APL a highly curable leukemia. However several complications are reported with this treatement the most serious and life threatening being ATRA syndrome. We aimed at identifying factors that could predict complications caused by ATRA during induction treatement of APL.
Patients: 42 patients with comfirmed APL(by t(15,17) and/or PML/RARA) treated at our institution (University hospital of Tunis) between January 1998 and June 2006 using two consecutive protocols: European APL93 trial (24 patients) until February 2004 and Spanish PETHEMA LPA99 trial (18 patients) more recently. Induction regimen consisted of ATRA 45 mg/m2/d until CR combined to DNR 60 mg/m2/d×3 + Cytarabine 200 mg/m2/d×7 (APL93) and Idarubicin 12 mg/m2 d2,4,6,8 (LPA99). Prednisone (0,5 mg/kg d1–d15) was added if WBC > 10 000/mm3 to prevent ATRA syndrome in LPA 99.
Results: Median age was 36 yr (7–64yr), M/F=16/26(0,61), median WBC was 2400/mm3(range 600–100 000/mm3). WBC>10 000/mm3 was noted in 14 patients (33%). Additional cytogenetic abnormalities were seen in 12/42(28%). Median Body Mass Index(BMI= weight/length2:N 20–25) was 24kg/m2(range 16–40kg/m2), BMI>30 was noted in 9 patients(8F and 1M).33 patients achieved CR (78,57%):18/24 (75%) in APL93 vs 15/18(83%) in LPA99.9 patients(21,42%) had early death. Causes of early death were:ATRA syndrome(6) and CNS haemorrhage (3). Complications due to ATRA were:ATRA syndrome(10), Scrotal ulcerations(3), Sweet syndrome(2), Perineal ulcerations(1), Pseudotumor cerebri (1). Prognostic factors for complications of ATRA(Fisher exact test) were:BMI>35 (p=0,055), induction treatment without cytarabine(LPA99 trial) (p=0,047), whereas age(p=0,74), gender (p=0,51), initial WBC (p=0,47), and additional cytogenetic abnormalities were not predictive. ATRA syndrome was more reported in patients with initial WBC>10 000 (p=0,08).
Conclusion: We found high BMI (>35) in female and treatement without Cytarabine to increase the risk of developping complications with ATRA.
Pegilated Liposomal Doxorubicin in Combination with Cyclophosphamide, Vincristine, Prednisone and Rituximab in Patients with Newly Diagnosed Diffuse Large B Cell NHL: Clinical Efficacy and Related Cardiac Safety.
Authors: Geraci Leonardo , Colangelo Mauro , Ranalli Roberto , Puglielli Serina , Nenna Caterina , Celeste Franco 
Published: October 2019

Abstract
Pegylated liposomal doxorubicin, (CAELYX; Schering Plough) was introduced because of its low or totally absent cardiotoxicity and greater penetration in tumor tissue. Based on differences in clinical pharmacokinetics and clinical studies, the dose for PLD is lower than the standard dose for doxorubicin and epidoxorubicin. This feature makes it suitable for use in older patients and/or those with previous heart disease suffering from diffuse large B-cell NHL, by including Caelyx in 30 mg/mq doses in the classic CHOP regimen, in place of conventional doxorubicin. In this single-centre study, the endpoint were the therapeutic response and the incidence of cardiotoxicity, assessed by means of echocardiogram (LVEF),before and after chemotherapy and at a later stage following the last chemotherapy cycle. Pegylated liposomal doxorubicin was administered in a dose of 30 mg/mq in association with standard doses of Cyclophosphamide 750 mg/mq, Vincristine 1,4 mg/mq, Prednisone 100 mg/mq p.o. day 1–5, and Rituximab 375 mg/mq at 21 day intervals.The trial enrolled 24 patients, aged between 65 and 83 (average age 75 years), in stage II-IV (15 patients in stage IV, 6 in stage III and 3 in stage II); in 65% of the patients, the International Prognostic Index was high-intermediate. An average of six chemotherapy cycles were administered per patients. No dose-limiting cumulative toxicity was observed. The objective responses observed were 85%, with 70% complete responses and 15% partial responses. The average duration of the response was 14 months (1.7–41.5 months). There was no decrease in LVEF associated with administration of pegylated liposomal doxorubicin. Pegylated liposomal doxorubicin in combination with Cyclophosphamide, Vincristine and Prednisone in addition to Rituximab, was found to be active and safe in this series of patients with diffuse large B-cell lymphoma with complete remission in 70% of the cases, without this affecting cardiac safety.
Placenta Derived Adherent Cells (PDACs) Suppress Tumor Cells of Diverse Origin.
Authors: Harbacheuski Ryhor , Paludan Casper , Murray Rose Ann , Mendillo Megan , Soler Jorge , Wang Jia-Lun , Ye Qian , Hofgartner Wolfgang , Edinger James , Kaplan Gilla , Hariri Robert 
Published: October 2019

Abstract
The placenta is a readily available and ethically non-controversial source of large amounts of therapeutic stem cells. We isolated adherent cells from the Umbilical Cord (UC) and the Amnion Chorion (AC) of term placentas. These Placenta Derived Adherent Cells (PDACs) displayed a cell surface phenotype of CD29+, CD44+, CD73+, CD90+, CD105+, CD200+, CD34−, and constitutively secreted IL-6, IL-8 and Monocyte Chemoattractant protein-1 (MCP-1). PDACs demonstrated in vitro pluripotency and suppressed T cell proliferation in both the allogeneic mixed leukocyte reaction, and the autologous EBV regression assay. Because progenitor cells have been described to inhibit tumor growth in some systems, the role of PDACs in tumor suppression was investigated.
EBV transformed tumor cells were cultured either alone, or with AC or UC PDACs. After 6 days, live (7-AAD− Annexin-V−) tumor cells were counted on a flow cytometer. Free growing tumor cells numbered 40,000. When tumor cells were co-cultured with AC or UC PDACs, the growth was suppressed to 10,000 cells, a suppression of 75%. We designed and tested a panel of tumor cell lines that included retinoblastoma (RB), histiocytic lymphoma (HL), chronic myelogenous leukemia (CML), and colon adenocarcinoma (CAC). The tissue origin of the selected tumor cell lines included neuronal tissue (retinoblastoma), epithelium (carcinomas) and the hematopoietic lineage (lymphomas and CML). Co-culture experiments showed that the growth of all tumor lines was suppressed more than 40%. When a transwell was introduced separating PDACs and tumor cells, contact dependency of suppression was 12% for HL, 22% for CML, 42% for CAC, and 51% for EBV transformed tumor cells.
These results indicate that PDACs may have therapeutic value with respect to certain cancers.