bluuebunny/crossref_metadata_2025_split huggingface dataset:
Casein Kinase CK2 Inhibition Results in Tumor Suppression.
Authors: Mohammad Hanan , Lindner Daniel j , Kalafatis Michael 
Published: October 2019

Abstract
Abstract 5052
Protein Kinase II (CK2) is a pleiotropic, and ubiquitous serine/threonine kinase taht utilizes both ATP and GTP as phosphate donors. Protein kinase CK2 mostly exists as a tetramer composed of two catalytic subunits α and α‘, which exists in heterogeneous or homogenous nature, and two regulatory β subunits. CK2 is a key regulator of signaling pathways involved in cell cycle, proliferation and apoptosis. It is consistently overexpressed in cancer tissue and capable of shuttling between cellular compartments but mainly localized in the nuclear matrix of cancer cells. CK2 is highly involved in apoptosis suppression, oncogene activation and tumorigenesis. It is also considered a bad prognostic marker in cancer tissue and is suggested to be a promising target for cancer therapy. In this study, we examined the effect, of a specific protein kinase inhibitor, and ATP competitor, 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole (DMAT), on the growth of various cancer types. We have reported DMAT as a potent cancer therapy. In vitro analysis of the viability of hematologic neoplasms and solid tumors, including human lymphoma U937, hormone dependent breast cancer MCF7, hormone independent breast cancer MDA-MB231 and MDA-MB468, and human cervical cancer HeLa cell lines, revealed marked reduction of cellular viability upon treatment with different DMAT concentration at varying time periods. Lymphoma cell line U937 showed an IC50 between 6 -12 μM. A sharp decrease in cancer cells growth was specifically observed following DMAT treatment of cervical carcinoma HeLa cell line with IC50 between 0.2-0.3 μM. Each of the breast cancer cell lines showed IC50 of 6, 10, and 20 μM DMAT for MDA-MB468, MCF7 and MDA-MB231 respectively. The more cancer cell lines we screen, the more evidence we have to suggest DMAT as a potential anti-cancer therapy. However, the specific mechanism of action of DMAT-inhibited-CK2 pathway in cancer ablation is not clear yet. Using Propidium-Iodide staining in conjunction with flow cytometry techniques, we analyzed and compared cell cycles of treated U937, MCF-7, MDA-MB231, MDA-MB468, and HeLa cell lines. Our data indicate that DMAT induces cell cycle arrest in HeLa cell line at G0/G1 phase. No effect on cell cycle was observed for all other cell lines tested. However, all cell lines underwent apoptosis following treatment with DMAT. Thus far our results suggest that DMAT can induce cell cycle arrest, apoptosis and maybe necrosis or multiple processes at the same time. We suggest that the mechanism of DMAT in cancer inhibition could be of multiple actions which further validate this molecule as a potent cancer therapy that could be suitable for clinical investigation.

Disclosures
No relevant conflicts of interest to declare.
ADAMTS13 ACTIVITY and VON Willebrand FACTOR LEVELS IN PATIENTS with Livedoid VASCULOPATHY.
Authors: da Costa França Andrea Fernandes Eloy , de Moraes Mazetto Bruna , Orsi Fernanda A. , de Paula Erich Vinicius , Machado Tania F.G.S , Souza Elemir M , Annichino-Bizzacchi Joyce Maria 
Published: October 2019

Abstract
Abstract 5064

Introduction
Livedoid vasculopathy is a rare skin disease caused by the extensive formation of microthrombi in dermis vessels, which leads to infarction and ulceration of the epidermis. The pathogenesis of livedoid vasculopathy is unknown, and hypercoagulation states have been implicated. Moreover, success using anticoagulation was reported in some patients. We hypothesized that decreased levels of ADAMTS13 activity and Von Willebrand factor (vWF) levels could contribute to the pathogenesis of local thrombus formation in livedoid vasculopathy.

Objective
Here we evaluated the levels of ADAMTS13 activity and vWF in patients with livedoid vasculopathy.

Patients and methods
Fourteen patients (93% female) with livedoid vasculopathy, median age of 41.5 years (22 - 48) were included in the study. All patients were evaluated for the presence of classical acquired and hereditary thrombophilia markers. In addition, vWF antigen levels (Elisa) and activity (collagen binding assays), as well as ADAMTS13 activity (evaluated by residual collagen binding) were evaluated.

Results
nine patients (64%) were carriers of the MTHFR C677T mutation (6 heterozygous and 3 homozygous); 1 patient was a carrier of factor V Leiden mutation, and 1 patient was a carrier of the FII G20210A mutation. None of the patients presented deficiency of antithrombin, protein C or S, and antiphospholipid antibodies were not identified in our study population. ADAMTS13 and VWF activities were normal in all patients. Median vWF antigen was 120.5U/dl (reference value of 40.0 - 232.0%), and vWF activity was 102.3% (reference value of 45.5 - 203.7%). ADAMTS13 activity was 138.9% (reference value of 56.0 - 227.2 %). Two patients had a history of thromboembolic diseases: one patient with 2 strokes and one patient with central retinal artery occlusion.

Conclusion
We show here that ADAMTS13 activity and vWF levels are not altered in patients with livedoid vasculopathy. The MTHFR C677T mutation is frequent in patients with livedoid vasculopathy but quantification of homocysteine levels is necessary to consider any relationship with this disease.

Disclosures
No relevant conflicts of interest to declare.
Hereditary Spherocytosis (HS) Associated with a Heterozygous MTHFR C677T Mutation and with Elevated Anticardiolipin Antibodies.
Authors: Noble Luis S. , Velazquez Maria , Gupta Anuradha , Landeros Mark M. , Herrada Juan 
Published: October 2019

Abstract
Abstract 5069

Background
Hereditary spherocytosis (HS) is a spectrum of inherited erythrocyte membrane defects that result in hemolysis and varying degrees of anemia, usually not associated with increased thrombotic risk. However, there is some concern about post-splenectomy thrombocytosis, since both arterial and venous thromboembolic events have been reported in patients splenectomized for HS.
A review of the medical literature revealed only a few cases of thrombosis associated with pregnancy and hereditary spherocytosis, and none of them had methyl tetrahydrofolate reductase (MTHFR) mutations or the presence of elevated anticardiolipin antibodies (both considered risk factors for thromboembolic disease).

Methods
Case report

Results
A 34-year-old Caucasian female with history of hereditary spherocytosis and splenectomy at age five, underwent evaluation for infertility. The patient was found to have a high titer of anticardiolipin antibodies and the presence of heterozygosity for the MTHFR C677T mutation. She denied any personal or family history of deep venous thrombosis. Subsequently the patient became pregnant. Because the combination of thrombophilic states appears to increase the risk of thromboembolic events, it was decided to start the patient prophyllactically with oral aspirin 81 mg daily, Foltx® (Folic acid 2.5 mg, cyanocobalamin 2000 mcg, and pyridoxine hydrochloride 25 mg), and heparin 5000 mg subcutaneously twice a day. On her most recent evaluation, at 26 weeks of pregnancy, no medical or obstetric problems have been observed.

Conclusion
Our case illustrates an unusual combination of thrombophilic states. Further studies are needed to evaluate the clinical significance of this association.

Disclosures
No relevant conflicts of interest to declare.
Thrombophilia in Retinal Vessel Thrombosis.
Authors: Herrada Juan , Gupta Anuradha , Landeros Mark M. , Vazquez Carlos 
Published: October 2019

Abstract
Abstract 5072

Background
Retinal vessel thrombosis (RVT) is the second most common retinal vascular disease after diabetic retinopathy, and is a common cause of visual morbidity. The role of thrombophilia in the pathogenesis of RVT remains under investigation.

Methods
Retrospective analysis. Between 2001 and 2009, the medical records and laboratory reports performed on patients (pts) with retinal vessel thrombosis who underwent thrombophilic evaluation were reviewed. The thrombophilic laboratory evaluation consisted of: Factor V mutation analysis, Factor II mutation analysis, Protein C activity, Protein S activity, antithrombin-III activity, Factor VIII activity, homocystein level, Methyl tetrahydrofolate reductase (MTHFR) C677T mutation analysis, and anticardiolipin antibodies.

Results
9 pts were identified. All but 2 pts were females. Median age at diagnosis was 50 years (31-78). Factor V Leiden was found in 1 pt. MTHFR C677T heterozygous mutation was present in 4 pts, and in 2 of these, hyperhomocystinemia was present as well. Anticardiolipin antibodies were elevated in 6 pts, and in 2 pts it was the only laboratory abnormality. One pt with hyperlipidemia had a negative thrombophilic laboratory testing.

Conclusions
Although newer laboratory methods are able to detect coagulation defects, their clinical relevance in retinal vessel thrombosis requires additional research.

Disclosures
No relevant conflicts of interest to declare.
Clinical Outcome of Patients with Myelophthisic Anemia Arising From Advanced Gastric Cancer.
Authors: Kwon Ji Yeon , Kim Han Jo , Kim Kyoung Ha , Kim Se-Hyung , Lee Sang-Cheol , Kim Hyun Jung , Bae Sang Byung , Kim Chan Kyu , Lee Nam Su , Lee Kyu-Taek , Park Sung Kyu , Won Jong-Ho , Hong Dae-Sik , Park Hee-Sook 
Published: October 2019

Abstract
Abstract 5095

Background
Although it is not common to encounter patients with myelophthisic anemia arising from advanced gastric cancer, clinical features and optimal treatment are not yet to be elucidated. Prognosis for gastric cancer patients with bone marrow metastases is extremely poor. The current study was performed to evaluate clinical outcome of patients with myelophthisic anemia arising from advanced gastric cancer.

Methods
We retrospectively reviewed the medical records of 26 advanced gastric cancer patients with bone marrow metastases between September 1986 and February 2009 at Soonchunhyang University Hospital.

Results
The median age was 46 years (range 24-61 yeras). All patients had poorly differentiated adenocarcinoma, including 17 signet ring cell carcinomas. The majority of the patients showed thrombocytopenia, anemia, and elevation of lactate dehydrogenase. Sixteen patients (61.5%) were received palliative chemotherapy with a median of 4 cycles. (range, 1-13 cycles). Median survival durations after bone marrow metastases for entire patients were 37 days (95% CI, 12.5-61.5 days). The median survival times from bone marrow involvement were 11 days in the best supportive care group (range 9.5-12.5 days) and 121 days (range 94.7-147.3 days) in the palliative chemotherapy group (p <0.001). Patients died of tumor progression (11 patients, 45%), brain hemorrhage (6 patients, 25%), infection (5 patients, 21%), and DIC (1 patient, 4%). There were no chemotherapy related deaths.

Conclusion
It is difficult to decide whether to proceed with aggressive treatment for gastric cancer patients with bone marrow metastases because of the hematologic findings, e.g. anemia, thrombocytopenia, and DIC. However, this study suggests that palliative chemotherapy should be actively considered in patients with myelophthisic anemia arising from advanced gastric cancer.

Disclosures
No relevant conflicts of interest to declare.
Low Incidence of Cardiac Siderosis in Heavily Iron Overloaded Egyptian Thalassemics.
Authors: El-Beshlawy Amal M. , Hamdy Mona Mohamed , Elgamrawy Mona , Azim Khaled Abdel , Salem Doria , Samir Ahmed , Eltagui Mona 
Published: October 2019

Abstract
Abstract 5110

Introduction
Myocardial siderosis in thalassemia major remains the leading cause of death in developing countries. Once heart failure develops, the outlook is usually poor with precipitous deterioration and death. Cardiovascular magnetic resonance (CMR) technology can measure cardiac iron deposition directly using the magnetic relaxation time T2*. This allows earlier diagnosis and treatment and help to reduce mortality from this cardiac affection.

Patients and Methods
89 β thalassemia patients (10 to 43 years, mean age of 20.78±6.36) were recruited in this study. All patients were receiving chelation therapy of subcutaneous desferroxamine. Evaluation of hemosiderosis was based on CMR, liver magnetic resonance R2 and serum ferritin.

Results
T2* values ranged between 4.3 to 53.8 ms with a mean of 28.50±11.74 ms among our study group. The left ventricular ejection fraction (LVEF) as measured by CMR ranged between 55 and 78%; mean=67.66±4.69%.and liver iron concentration (LIC) ranged between 1.5 to 56 mg/g dry weight with a mean of 26.13±13.37 mg/g. Serum ferritin varied among our study group from 533 to 22363ng/ml; mean=4514.27±2847.58ng/ml with 83.15% above 2500ng/ml. The prevalence of myocardial siderosis (T2*<20ms) among our patients was 22/89 patients (24.7%) aged 20.86±7.54 years with a mean T2* value of 12.718±4.36ms and LVEF of 68.59 ±5.84%. LIC and serum ferritin results were 30.85±13.48 mg/g and 6122.86±4185.67ng/ml respectively. There was no correlation between T2* results and the age, LVEF, LIC and serum ferritin of this group (P=0.651, P=0.085, P=0.999 and P=0.627 respectively). Those patients with severe cardiac siderosis (T2*<10ms) constituted 7/89 (7.9%) with a mean age of 18.43±4.35 years. Although these patients had a mean T2* of 7.8±1.73 ms, the LVEF value was 65.14±6.20 % and only one patient had clinical cardiac disease (T2*=4.3 ms and LVEF =55%). LIC and serum ferritin results were 29.84±16.99mg/g and 7202.14±6953.79ng/ml respectively. In this group of severe cardiac siderosis, T2* was not correlated to age (P=0.5), LVEF (P=0.144), LIC (P=0.969) and serum ferritin (P=0.818).

Conclusion
Low prevalence of myocardial siderosis in the Egyptian thalassemic patients in spite of the very high serum ferritin. In severely iron overloaded patients the cardiac function was not affected. T2* is the best test that can identify at risk patients who can be treated with optimization of their chelation protocols. The possibility of a genetic component for the susceptibility of cardiac iron loading in our population should be considered.

Disclosures
No relevant conflicts of interest to declare.
Regulation of Complement Activation by Thrombomodulin.
Authors: Delvaeye Mieke , DeVriese Astrid , Moons Michael , Esmon Naomi , Esmon Charles , Conway Edward M. 
Published: October 2019

Abstract
Abstract 5127
Thrombomodulin (TM) is an integral membrane glycoprotein, ubiquitously expressed by vascular endothelial cells. Its epidermal growth factor (EGF)-like repeats amplify thrombin-mediated generation of activated protein C and activated thrombin activatable fibrinolysis inhibitor, thereby suppressing coagulation, inflammation and fibrinolysis, and inactivating the anaphylatoxins, C3a and C5a. TM also has direct anti-inflammatory properties, interfering with leukocyte adhesion, and preventing complement activation via its lectin-like domain. We recently established that TM is a physiologically important negative regulator of the alternative pathway (AP) of complement activation, defects of which increase the risk of the thrombotic microangiopathy, atypical hemolytic uremic syndrome. In this report, we assessed the role of TM in the other complement activation pathways. In serum, TM interferes with classical pathway (CP) mediated erythrocyte cell lysis, and protects against CP-induced cell death. TM co-precipitates with C4b, and enhances its inactivation and cleavage to C4c and C4d by complement factor I in the presence of the cofactor C4b binding protein. TM also interferes with the coagulation complement pathway by interfering with thrombin cleavage and activation of C5 to C5a. Overall, TM negatively regulates complement via the major recognized pathways. The findings implicate defects in TM in a wide range of diseases in which complement plays a role, and underlines the potential of TM as a therapeutic target.

Disclosures
No relevant conflicts of interest to declare.
Endothelial Progenitor Cells(EPC) in Peripheral blood in Diabetic Foot with and without PAD.
Authors: Krutikov Alexander , Anisimov Sergey , Gabaidulina Malika , Meln Irina , Grineva Elena , Vavilov Valery , Semernin Eugene , Zaritskey Andrey 
Published: October 2019

Abstract
Abstract 5130
EPC is not very well defined population. These cells have either angiopoietic or angiostimulating function, the latter seems to be more relevant. It is well known that
Mobilization of EPC to peripheral blood is decreased in diabetic rats. From the opposite, ischemia proved to stimulate mobilization. That is why, we decided to study EPC in diabetic patients with and without PAD

Patients and methods
40 pts with diabetes(type I- 4, type II-36) were studied. Duration of diabetes -1-46 years. The duration of more than 10 years was in 57% patients. Age- 49-73 years(mean age- 62 years). The patients were divided into two groups- diabetic foot without PAD(25 pts) – Group A, and diabetic foot with PAD- group B. PAD was diagnosed with sonography, duplex sonography and Rx arteriography. Normal volunteers were use as controls(mean age 51.6+2.0)
CD34+ and CD133+ cells were numerated with CytoFlow(BD).
5 Day CFU-Hill Colony Assay- non-adherent mononuclear cells (MNCs) was used to study EPC
In this method, peripheral blood MNCs are plated on fibronectin-coated dishes (6-well). After a 48 h pre-plating step to deplete the sample of adherent macrophages and mature endothelial cells, the non-adherent cells are removed and re-plated on fibronectin-coated dishes (24-well). Unique colonies that are formed in the 5 Day CFU-Hill Colony Assay are referred to as colony-forming unit-Hill colonies (CFU-Hill colonies) or colony-forming unit-ECs (CFU-ECs). Count the number of colonies per well for each sample. CFU-Hill colonies are defined as a central core of round cells with radiating elongated spindle-like cells at the periphery. Colonies without the CFU-Hill morphology may also be present but are not scored as CFU-Hill colonies. CFU-Hill Colonies are fixed with methanol and stained with a Giemsa solution. Plasma concentration of VEGF was studied by ELISA

Results
EPC colony forming ability in group A was 4.0+ 0.7, in group B-27.4+3.9. The differences between these two groups is highly significant(p 0.001). Low EPC level in diabetic neuropathy is probably related to decreased mobilization(G.Fadini e.a.2006). Rather unusual was higher EPC level in group B. It was shown that age-related decrease in EPC is due to decline in HIF-1 signaling(M. Hoenig e.a 2008). Probably, diabetic defect of mobilization is partly overcome with ischemia induced up-regulation of HIF-1 and VEGF. EPC in group B patients does not differ from controls(26.1+6.5).
There were now correlations between EPC number and the number of either CD34+, CD133+, or KDR+ cells. We also failed to find any correlations between VEGF and EPC

Conlusion
EPC number in peripheral blood in diabetic patients without PAD is severely decreased. Diabetic patients with PAD have near normal EPC number. Thus, ischemia in diabetic patients is unable adequately mobilize EPC

Disclosures
No relevant conflicts of interest to declare.
Autologous Hematopoietic Stem Cell Transplantation (HCT) is a Safe and Effective Treatment for Primary Plasma Cell Leukemia: The CIBMTR Experience.
Authors: Mahindra Anuj , Vesole David , Kalaycio Matt E. , Vela-Ojeda Jorge , Shrestha Smriti , Zhang Mei-Jie , Dispenzieri Angela , Milone Gustavo A. , Lonial Sagar , Hari Parameswaran N. 
Published: October 2019

Abstract
Abstract 532

Primary Plasma cell leukemia (PCL) is a rare plasma cell disorder characterized by an aggressive clinical course. The efficacy of autologous and allogeneic HCT in PCL is uncertain due to the small number of patients that have been reported in the literature. To determine the potential for long-term disease control using HCT in PCL, we performed a retrospective review of 160 patients with primary PCL who received autologous (n=107), allogeneic (n=52) or syngeneic (n=1) HCT and were reported to the CIBMTR between 1995 and 2006. Kaplan–Meier analysis was used for overall survival (OS) and progression free survival (PFS). Cumulative incidence estimates of non-relapse mortality (NRM), relapse, acute and chronic GVHD were calculated.
Median age at the time of autologous HCT was 57 years (range, 32-74 years) and allogeneic HCT was 48 years (range, 24-62 years). Median time from initial treatment to autologous HCT was 7 months and allogeneic HCT was 6 months. At the time of transplant, in the autologous HCT group, 19% patients were in complete remission, 56% in partial remission and 1% had relapsed/progressive disease; in the allogeneic HCT group, 17% were in complete remission, 46% in partial remission and 10% had relapsed/progressive disease. In the allogeneic HCT group, 83% of the patients received myeloablative conditioning regimens and 17% received nonmyeloablative/reduced-intensity conditioning. The rate of acute GVHD was 35% (95% confidence interval [CI], 22%-49%) and the rate of chronic GVHD at 3 years was 27% (95% CI, 13%-40%). After a median follow-up of 38 months, 20 of the 52 patients (38%) are alive in the allogeneic HCT group and 68 of the 107 pts (64%) are alive in the autologous HCT group (Figure 1). Progressive disease accounted for 38% of the deaths in the allogeneic HCT group and 86% of the deaths in the autologous HCT group. The outcomes are summarized in table 1. The remarkable overall survival of patients after autologous HCT in this analysis is noteworthy and indicates that autologous HCT is a safe and acceptable treatment option for patients with primary PCL. Although relapse rates are lower, allogeneic HCT carries a much higher risk of NRM and should be considered primarily in the context of a clinical trial.

Disclosures:
Lonial: Celgene: Consultancy; Millennium: Consultancy, Research Funding; BMS: Consultancy; Novartis: Consultancy; Gloucester: Research Funding.