bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Umbilical Cord Blood Stem Cell Therapy for Regenerative Medicine Applications
Authors: Weinthal Joel , Praught Melanie , Brown Heather 
Published: April 2020

Abstract
Over the past 20 years umbilical cord blood (UCB) has become valuable source of hematopoietic stem cells for use in transplantation to treat malignancies, blood disorders and genetic diseases. Cord blood stem cells have shown promising results in animal regenerative medicine studies for the repair of damaged or diseased tissues outside of the hematopoietic lineage. Family UCB banks provide collection and storage services for families to store their child’s UCB for clinical use. This study compared the release of UCB units from one family bank (Cord Blood Registry, CBR) for regenerative medicine versus traditional transplantation since the release of its first UCB unit for regenerative medicine in 2005. UCB was collected from the placenta of consenting mothers and transported to the processing facility from all 50 states and over 80 countries. The UCB was separated into a mononuclear cell fraction from the red blood cells and other non-engrafting cells. The processed UCB is stored in vapor-phase liquid nitrogen at −195° C until requested for use. To date, 230,000 units have been stored. Prior to release, viability and percent CD34+ (or CFU) content were assessed by the treating institution. Through July 2008, a total of 82 UCB units were released for clinical use, 47 of these units (57%) have been used for traditional transplantation and 35 (43%) have been used for regenerative medicine. From January 2005 through July 2008, 47 UCB units were released, 12 (26%) were used in traditional transplantation and 35 (74%) were used in regenerative medicine applications. Over this period the bank experienced a mean of 338% percent growth per year in the release of UCB units for regenerative medicine. The indications for regenerative medicine autologous infusions were cerebral palsy (24 units), brain injury (4 units), type 1 diabetes (6 units), and a rare immune disorder (1 unit). All patients in the regenerative medicine category did not receive any myeloablative chemotherapy or radiation. Released UCB units were stored a mean of 37 months prior to use, the mean CD34+ percent of TNC was 0.53% and mean viability was 95.9%. These data indicate that regenerative medicine applications utilizing autologous cord blood stem cells represent a significant and growing percentage of all treatments facilitated by a family cord blood bank. Regenerative medicine treatments for cerebral palsy and type 1 diabetes have the potential to impact many lives given that 10,000 cases of cerebral palsy and 13,000 cases of type 1 diabetes are diagnosed each year which compares to 2,500 cases of childhood leukemia and 650 cases of neuroblastoma, two common indications for pediatric transplantation. Further analysis is needed to assess the clinical outcomes which will provide background for larger clinical trials in the future.
Prominent Prevalence of Coagulase-Negative Staphylococcus Bloodstream Infections in Neutropenic Hematology/Oncology Children with Central Venous Catheter
Authors: Lee Young-Ho , Lim Yeon Jung , Song Soon-young , Kim Ji-hye , Oh Sung-hee , Koo Hong Hoe 
Published: April 2020

Abstract
A retrospective analysis was performed on febrile neutropenic episodes in children with hematologic and oncologic diseases from 2005 to 2008. We reviewed total 255 febrile episodes occurred during the 3-year period in a total of 114 patients. Twenty-eight episodes of bacteremia occurred during neutropenic period in a total of 16 patients. All these patients had central venous catheter. There were 18 febrile episodes of Grampositive bacteria (64.3%), 9 episodes of Gram-negative bacteria (32.1%), and 1 episode of Candida (3.6%). The isolated organisms were as follows: Coagulase-negative Staphylococcus (CNS, N=17, 60.7%), Staphylococcus aureus (N=1, 3.6%), Enterobacter spp. (N=2, 7.1%), Pseudomonas spp. (N=2, 7.1%), Klebsiella (N=2, 7.1%), E. coli (N=2, 7.1%), Acinetobacter (N=1, 3.6%), Candida. (N=1, 3.6%). The bloodstream infection with CNS were more prevalent in children with Chemo-port (12 episodes in 6 from 34 patients, 17.6%) than in children with Hickman catheter (5 episodes in 5 from 22 patents, 22.7%), even though statistically not significant. In antibiotic susceptibility tests, all gram positive bacteria were resistant to penicillin and oxacillin, and sensitive to vancomycin and teicoplanin. In the case of Gram-negative bacteria, resistant rates to amikacin, gentamicin, imipenem, and piperacillin/tazobactam were 4.8%, 38.1%, 14.3%, and 42.9%, respectively. Based on this retrospective analysis, which reflects predominance of CNS bacteremia in febrile neutropenic patients, more emphasis needs to be laid on the empirical antibiotic regimen including vancomycin or teicoplanin as well as the strict skin preparations during procedures in children with central venous catheter.
Manageable Side Effects of Intravenous Iron in a Community Practice
Authors: Brown Nicole , Henry David H. , Ford Patricia A. 
Published: April 2020

AbstractOur community hematology oncology practice uses intravenous (IV) iron in a wide variety of patients. A review of the literature on the adverse events (AE) of IV iron found 0.0–32.0% of patients were experiencing an AE with 0.0–0.5 events per patient. In our experience with IV iron, we felt that the actual incidence of AE was much higher than reported. Between June 2006 and April 2007, 156 patient surveys were completed by a total of 120 patients. Surveys were given to patients who had received IV iron in the past week. Those who experience adverse events were asked to note the type, onset, duration and intervention used to alleviate symptoms. Six patients were excluded for reporting symptoms occurring prior to treatment or completing the survey immediately after IV iron treatment. Of the remaining patients, 100 were female and 14 were male with an average age of 48.9 years (17–95 years). Eighty-six patients received iron sucrose, 22 sodium ferric gluconate and 6 iron dextran (InFed). In our patients, 48.2% experienced at least one AE with an average of 1.3 symptoms per patient (see table). The majority of these events (94.5%) were delayed and mild or moderate with only 5.5% of patients requiring a visit to the hospital or physician’s office. Common side effects were muscle or bone aches, dizziness, numbness, tingling and swelling of the hands and feet, abdominal pain and nausea/vomitting. There was no statistically significant difference in the number or severity of AE related to the different preparations. In our experience, AE occur at an increased frequency compared to the published literature. We feel it is important for health care providers to be aware that AE are likely to occur, but that they are usually minor and quite manageable without the need for physician intervention. In our practice the nurses trained in chemotherapy are well equipped to handle most events that arise. We find IV iron to be an extremely useful treatment for patients suffering from both absolute and functional iron deficiency and offer this data as evidence that parenteral iron is safe in a wide variety of patients.Comparison of AE Iron Sucrose n=86 Sodium Ferric Gluconate n=22 Iron Dextran n=6 Our Study n=114 Previously Reported Muscle or bone aches 17.4% 22.7% 50.0% 20.2% 0.0–3.8% Dizzy/Lightheadedness 16.3% 22.7% 33.3% 18.4% 0.0–0.9% Numbness/Tingling in hands/feet 14.0% 9.1% 16.7% 13.2% N/A Swelling in hands/feet 12.8% 13.6% 16.7% 13.2% 0.0–12.9% Stomach pain/cramping 10.5% 18.2% 16.7% 12.3% 0.0–4.5% Nausea/vomiting 10.5% 13.6% 16.7% 11.4% 0.0–25% Itching 10.5% 4.5% 16.7% 9.6% 0.0–1.5% Chest tightness/discomfort 4.7% 9.1% 0.0% 5.3% 0.0–1.0% Shortness of breath 3.5% 13.6% 0.0% 5.3% 0.0–1.5% Facial Flushing 3.5% 0.0% 0.0% 2.6% 0.0–.3% Hives 1.2% 4.5% 0.0% 1.8% 0.0–6.45% Other 12.8% 13.6% 50.0% 14.9% 0.0–30.0% Any symptom 44.2% 59.1% 66.7% 48.2% 0.0–32.26% Total symptoms 1.2 symptoms/patient 1.5 symptoms/patient 2.2 symptoms/patient 1.3 symptoms/patient 0.0–.45 symptoms/patient
Mega-Analysis of 50 Years of Diagnosis and Therapy of Childhood Acute Lymphoblastic Leukemia in Bydgoszcz, Poland: From Prednisolone Therapy to Microarray Studies
Authors: Styczynski Jan , Jatczak-Gaca Agnieszka , Debski Robert , Koltan Andrzej , Wysocki Mariusz 
Published: April 2020

Abstract
Background: The beginnings of pediatric oncology in Bydgoszcz, Poland dates back to the year 1958. The first patient was treated with prednisolone only.
Objective: Analysis of results of childhood acute lymphoblastic leukemia therapy in Bydgoszcz region in 1958–2008.
Patients and methods: A total number of 570 children were diagnosed and treated over the period of 50 years, including: 215 children treated with different drugs and combinations in 1958–1972, 49 children treated with Memphis V–VII protocols in 1976–1983, 114 children treated with ALL-BFM83 or ALL-BFM86 protocols in 1983– 1995 and 192 children treated with ALL-BFM90, New York I–II or ALL-IC-2002 between 1995–2008.
Results: A number of patients with „events” in respective time periods was: 205/215 (95.3%, in 1958–1972); 44/49 (89.8%, in 1976–1983), 54/114 (47.4%, in 1983–1995), 56/192 (29.2%, in 1995–2008). The values of 5-year pEFS in consecutive therapeutic periods were: p=0.012±0.008 (1958–1972), p=0.102±0.043 (in 1976–1983), p=0.526±0.047 (in 1983–1995), p=0.700±0.037 (in 1995–2008) (p&lt;0.0001). A median survival time was, respectively: 0.8 year (for patients treated in 1958–1972); 1.8 year (in1976–1983); 5.7 years (in 1983–1995); 7.4 years (for patients treated in 1995–2008).
Conclusions: Complex therapy based on international strategy of multiagent total therapy and supportive care, has led to an improved long-term survival in childhood ALL in Bydgoszcz region, Poland, from 1% in sixties up to 70% nowadays
Figure 1. pEFS in ALL with respect to time period Figure 1. pEFS in ALL with respect to time period
Assessment of the Anemia Work up Prior to the Use of Erythropoiesis Stimulating Agents (ESA) in Cancer Patients Undergoing Chemotherapy in a Community Oncology Practice
Authors: Davila Carine , Brown Nicole , Rossi Suzanne , Henry David H. 
Published: April 2020

Abstract
Introduction: Patients undergoing chemotherapy frequently experience chemotherapy induced anemia, which is commonly treated with erythropoiesis stimulating agents (ESAs). However, patients undergoing chemotherapy may also have anemia due to other factors. This study describes how often a proper anemia workup was performed to ensure that the patient’s anemia is due to chemotherapy and not renal insufficiency or iron, B12, or folate deficiency, before administering ESAs in a community hematology-oncology practice of 8 physicians.
Patients and Methods: Medical charts of 278 cancer patients receiving chemotherapy between January and June 2007 who were also given injections of either darbepoetin alfa (Aranesp) or epoetin alfa (Procrit) during the same time period were reviewed. Abnormal levels for each measure were defined as follows: ferritin (under 100ng/mL), B12 (under 200pg/mL), folate (under 5ng/mL), creatinine (over 1.4mg/dL), reticulocyte count percentage (over 5%), C-reactive protein (over 5mg/dL), erythrocyte sedimentation rate (over 20mm), and erythropoietin (over 20mU/dL).
Results: N=278 Patients
Test Performed Not Performed Normal* Abnormal* *Percentages shown in these two columns indicate the percentage of patients in which the test result was normal or abnormal out of the patients who had the test performed. Ferritin 85.5% (136) 14.5% (23) 42.8% (119) B12 96.4% (132) 3.6% (5) 50.7% (141) Folate 94.7% (126) 5.4% (7) 52.2% (145) Reticulocyte count 91.9% (125) 8.1% (11) 51.1% (142) Creatinine 89.1% (246) 10.9% (30) 0.7% (2) C-reactive protein 20.8% (5) 79.2% (19) 91.4% (254) Erythrocyte sedimentation rate 75% (3) 25% (1) 98.6% (274) Erythropoietin 28.9% (13) 71.1% (32) 83.8% (233)
Conclusion: We conclude that a significant number of patients do not have a proper anemia workup prior to ESA use (or before continued ESA after the first dose). In those patients who did, some laboratory results indicate that there may be another cause for the anemia, in addition to chemotherapy such as iron, B12, or folate deficiency, or renal insufficiency. Given the recent controversy over ESA use, it is particularly important to consider other treatment options prior to administering ESAs, especially given the cost-effectiveness of some of these treatments (FDA Alert: Erythropoietin Stimulating Agents 2006). Oncologists may want to consider identifying and treating other causes of anemia in their cancer patients on chemotherapy prior to, or in conjunction with, ESA use.
Stem Cell Factor Signaling Collaborates in the Development of FIP1L1/PDGFRα Induced Chronic Eosinophilic Leukemia in a Murine Model
Authors: Yamada Yoshiyuki , Rothenberg Marc E , McBride Melissa , Sanchez-Aguilera Abel , Cancelas Jose 
Published: April 2020

Abstract
We have previously demonstrated the synergistic role of stem cell factor (SCF) in systemic mastocytosis associated with FIP1L1/PDGFRA (F/P)- chronic eosinophilic leukemia (CEL) (Yamada Y et al., Blood 2008). The aim of this study is to determine if SCF is also required for eosinophilia development in CEL. First, F/P- or vector control-transduced bone marrow hematopoietic stem cell/progenitors (BM-HSC/P) were cultured in SCF in the presence of hydrocortisone (10−5M, HC-SCF) for 2 or 3 weeks. Expression of F/P in HSC/P induced a 27,000-fold higher cell expansion in the presence of HC-SCF compared with HC-SCF -cultured control vector-transduced HSC/P. The cultured cells were then assayed in an IL-5-containing methylcellulose for analysis of CFU-Eosinophil formation, while the culture was continued with SCF in the absence or presence of HC. Only F/P+ HSC/P formed CFU-Eosinophil after ex-vivo culture in the presence of SCF (19 ± 2.2 CFU-eosinophils/105 cells) and HC-SCF-cultured BM-HSC/P quickly differentiated into mast cells after deprivation of HC (98% c-kit+/EGFP+ cells at two weeks of culture after HC withdrawal), suggesting that SCF in collaboration with F/P fusion, may expand progenitor cells of both eosinophil and mast cell lineages. In addition, we analyzed the role of SCF/ckit signaling in disease development of F/P+ CEL in vivo. CEL mice were developed using retroviral introduction of F/P fusion into HSC/P of IL-5 transgenic mice as previously reported (Yamada Y et al., Blood 2006). CEL mice were treated with a blocking anti-c-kit antibody, ACK-2, or an isotype-matched control antibody. ACK-2 treatment suppressed the circulating leukocyte count, eosinophil count and spleen weight significantly in CEL mice, whereas control (vector control-IL-5 transgenic BM-HSC/P transplanted wild type mice) did not show significant diference between ACK-2 treatment and isotype control one (Table). These results suggest that SCF signaling is required for eosinophilic leukemia development induced by FIP1L1/PDGFRa.
Table Circulating total leukocyte and eosinophilc counts and spleen weight of mice treated with antibodies
Control CEL isotype-control ACK-2 isotype-control ACK-2 Data are shown as mean ± SD, **p &lt; 0.001 compared with isotype control, † p&lt;0.001 compared with control WBC, white blood cells, CEL, chronic eosinophilic leukemia. WBC(mm3) 8805±4377 5480±1433 176278±1210† 9602±12177±68.3** Eosinophil(mm3) 2609±671 804±235 29940±18735† 3480±4292±68.3** Spleen weight (mg) 137±11.3 89.9±211.2 2±11.2** 222.8±68.3**
Proteome Analysis of Apoptotic MR2 Cells, Acute Promyelocytic Leukemia Cell Line with All-Trans Retinoic Acid Resistance, Induced by Arsenic Trioxide
Authors: He Pengcheng , Zhang Mei , Wang Xiaoning , Wang Huaiyu , Xi Jieying , Li Jing , Wu Di , Wei Kaihua , Wang Hongli 
Published: April 2020

Abstract
Although all-trans retinoic acid(ATRA) provides complete remission in 90% patients with untreated acute promyelocytic leukemia(APL), it becomes ineffective to quite a few APL patients who have received ATRA before when their disease relapsed and used ATRA again. Arsenic trioxide(ATO) can make APL patients with ATRA-resistance obtain complete remission again by inducing APL cells apoptosis. However, the molecular mechanisms of apoptosis in ATRA-resistance APL cells induced by ATO remain unclear. For this reason, we take the apoptotic MR2 cells (APL cell line with ATRA-resistance) induced by ATO as a model, to screen and identify the proteins related with ATO-induced apoptosis by comparative proteomics. After MR2 cells were dyed with annexin V and PI staining, the percentage of the apoptotic MR2 cells induced by 1.0μmol/L ATO for 0h, 6h, 12h, 24h and 48h respectively was detected by Flow cytometry. The results showed that the majority of the apoptotic cells were in the earlier and later stage of apoptosis respectively, when MR2 cells were treated with ATO for 24 and 48 hours in sequence. The total proteins of MR2 cells of the control group, the earlier stages apoptosis group and the later stages apoptosis group were separated by two-dimensional electrophoresis(2-DE) respectively. Then, the differences in proteome profile among three groups were analyzed by ImageMaster™ 2D Platinum software. 14 protein pots were selected to be identified by Matrix-assisted laser desorption/ionization time of flight-mass spectrometry(MALDI-TOF-MS), in which the quantity of the protein differentially expressed was more than two times(≥2 or ≤0.5) among MR2-0h, MR2-24h and MR2-48h cells’ 2-DE map. However, only 11 proteins were successfully identified and their definite information was obtained. Among them, there were 8 proteins that were all probably involved in the mechanisms of apoptosis in MR2 cells and they were Calreticulin(CRT), Heat shock 70 kDa protein(HSP70), High mobility group protein B1(HMGB1), Ran-specific GTPase-activating protein(RanGAP1), Elongation factor 1-beta(EF-1β), Beta-tubulin, Cofilin-1, and Prolyl 4-hydroxylase(P4H) respectively. CRT was probably related with the early stage of apoptosis in MR2 cells, while RanGAP1 and HSP70 might related with the late stage of apoptosis in MR2 cells. Moreover, so far there was no related report on the roles of CRT, HMGB1, RanGAP1, cofilin-1 and beta-tubulin in the mechanisms of APL cells apoptosis. These differential proteins identified provide the new clues for further researching the molecular mechanisms of apoptosis in the ATRA-resistance APL cells induced by ATO.
Coordination of Fenretinide-Induced Apoptosis by Stress-Responsive Regulators in Leukemia Cells
Authors: Wang Kankan , Fang Hai , Xiao Da-Kai , Zhu Xue-Hua , He Miao- Miao , Pan Xiao-Ling , Chen Sai-Juan , Zhang Ji 
Published: April 2020

Abstract
Pharmacological intervention affecting intracellular redox balance often results in oxidative stress-mediated apoptosis, which also represents a new direction for cancer therapeutic designs. However, mechanistic links between redox signals and their downstream effects on apoptosis have not yet been elucidated in cancer cells. Here, we report a detailed analysis of fenretinide-induced apoptosis in leukemia-derived cells through a systems approach, integrating experimental and computational methods together with advanced data mining tools. Robust transcriptome profiling reveals numerous stress-responsive events at the temporal and spatial levels, including oxidative stress, endoplasmic reticulum stress/unfolded protein response, translational repression, proteasome activation, and apoptosis induction. Moreover, stress-responsive transcription factors, as highlighted by NRF2 and HSF1, play prominent roles in the configuration of these relevant events. Several lines of evidence suggest that these stress-responsive regulators and thus their target genes are involved not only in converting oxidative signaling into downstream effects but also in coordinating the progression of cell apoptosis. This study provides a roadmap for understanding oxidative stress-mediated apoptosis in cancer cells, which may be further developed into more sophisticated therapeutic protocols, as implicated by synergistic induction of cell apoptosis using proteasome inhibitors with fenretinide.
Identification and Purification of Leukemic Stem-Like Cells in Acute Myeloid Leukemia Cell Line
Authors: She Miaorong , Niu Xingqing , Chen Xilin , Kunyuan Guo , Zhou Maohua , He Yanjie , Le Yi 
Published: April 2020

Abstract
Acute myeloid leukemia (AML) is initiated and maintained by a rare population of (leukemic stem cells) LSCs. LSCs play the central role in the relapse and refractory of AML and highlight the critical need for the new therapeutic strategies to directly target the LSC population for ultimately curing leukemia which is it is important to identify and study LSCs. However, relatively little is known about the unique molecular mechanisms of survival and self-renewal of LSCs because of very small number of LSCs in bone marrow. In this study, we investigated whether established leukemia cell lines contain LSCs. We showed that leukemia cell line contain leukemic stem-like cells which have been phenotypically restricted within the CD34+CD38− fraction. We demonstrated that CD34+CD38− cells could generate CD34+CD38+ cells in culture medium and had proliferation function. Moreover, CD34+CD38− cells had self-renewal potential both in vitro soft agar colonies formation assay and in vivo NOD/SCID mouse xenotransplant model serial transplantation. Furthermore, CD34+CD38− cells isolated from leukemia cell line were found resistant to conventional chemotherapy and NK cells-mediated cytotoxicity and these were related to up-regulation of ABCG2 and MRP-1 and antiapoptotic proteins of Bcl2. Down-regulation of NKG2D ligand also played a critical role in NK cytotoxicity resistance. Taken together, our studies provide a novel cell model for leukemic stem cells research. Our data also shed light on mechanism of double resistant to resistant to chemotherapy and NK cell immunotherapy, which was helpful for developing novel effective strategies for LSCs.
Immnuoregulatory Effect of Human Mesenchymal Stem Cell Is Mediated Via STAT3 Molecule
Authors: Yoon Jinsun , Kim Seoju , Kim Eun Shil , PARK Byoungbae , Choi Junghye , Kim Insoon , Kim Byoung Kook , Lee Young 
Published: April 2020

Abstract
The best curative treatment modality in hematologic malignancies is allogeneic hematopoietic stem cell transplantation (HSCT). Graft-versus-host disease (GVHD) is a major obstacle of allogenic HSCT. Bone marrow derived human mesenchymal stem cells (MSCs) is known to have immunoregulatory effect in vitro and in vivo via inhibiting alloreactive T lymphocytes, leading to their clinical use for the prevention of GVHD in HSCT. However, the molecular mechanism of immunoregulatory effect of human MSCs is not fully understood. In this study we investigated the signaling of immunoregulatory effect by co-culture of human MSCs with lymphocytes. The proliferation of allogeneic T cells was strongly inhibited. The fraction of CD4+CD25+Foxp3+ cells (Treg cells) was increased, while the fraction of CD4+, CD8+, CD25+ was decreased. In addition, induction of Th1 to Th2 shift was observed. Western blot study showed that phosphorylation of STAT1, STAT3, STAT6 was up-regulated, but STAT1, STAT4, ERK, AKT, NF-κB (p65, p50 subunits) was down-regulated. While expression of STAT3 was observed in culture of MSCs only, no expression of STAT3 was shown in co-cultured human MSCs with lymphocytes. In order to validate our results, expression of STAT3 in human MSCs co-cultured with lymphocytes was ablated using small interfering RNA. As a result, inhibition of CD4+CD25+FoxP3+ cells, proliferation of allogenic T lymphocytes, inhibited induction of Th1 to Th2 shift and proliferation of CD4+, CD8+, CD25+ cells. Furthermore, expressions of Th1 and Th17-related cytokines were increased, while expressions of Th2-related cytokines were decreased. In summary, these results suggest that STAT 3 may be an indispensable molecule in the immunoregulatory effects in human MSCs via modulation of regulatory T cells.