bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Novel Peptide Ligands Targeting α4β1 Integrins on Patient Lymphoma Cells
Authors: Tseng Harry , Xiao Wenwu , Huang Wenzhe , Wun Ted , Lam Kit 
Published: October 2019

Abstract
Abstract 4854
Peptides are promising cancer-targeting agents—they are small, chemically stable, easy to synthesize and can be readily conjugated to toxins, radionucleotides, or drugs. The “one-bead one-compound” (OBOC) combinatorial libraries developed in the Lam lab consist of millions of beads, each displaying one unique peptide entity. Through high throughput screening peptide combinatorial libraries against cancer cell lines, peptides can be selected and engineered to recognize some certain receptors on the cell surface. From our previous screen, we observed that the LLP2A peptide sequence bound to the α4β1 integrin on the cell surface of a variety of malignant lymphoid cell lines. We hypothesize that more specific ligands against the α4β1 integrin on human patient lymphoma cells could be identified through screening focused LLP2A libraries. Two OBOC-focused combinatorial libraries based on the LLP2A peptide sequence were designed, synthesized and screened against human patient lymphoma cells to search for ligands with higher binding affinity. We selected the candidate peptide sequences that displayed a higher strength for the patient lymphoma cells using the whole cell binding assay, an in vitro approach for quantitating the strength of peptide interaction with cell surface molecules on the cancer cells. We are currently analyzing the data to determine the specific sequence requirements for higher affinity binding. Further assessment of the affinity and kinetics of integrin-peptide binding will be performed using flow cytometry.

Disclosures:
No relevant conflicts of interest to declare.
Influenza A H1N1 Pandemic Infection In Onco-Hematologic Patients
Authors: Pierrotti Ligia Camera , Bellesso Marcelo , Garcia Cilmara Polido , Pereira Juliana , Atta José Antonio , Hajjar Ludhmila Abrahão , Hoff Paulo Marcelo Gehm , Chamone Dalton FA , Abdala Edson 
Published: October 2019

Abstract
Abstract 4869

Background:
Epidemiological, virological and clinical data about H1N1 pandemic infection in immunocompromised patients are needed.

Objectives:
To describe a series of onco-hematologic patients with H1N1 pandemic infection who required hospitalization.

Method:
Review from institutional database and electronic patients charts. Specific diagnosis defined as a positive nasal swab PCR. Flu syndrome defined as fever, cough and/or sore throat; severe respiratory disease as fever higher than 38°C, cough and dyspnea.

Results:
From July 24th to September 30th 2009, 114 patients were investigated; 18 (15.8%) was confirmed and 9 were onco-hematologic patients. Hematological diseases were: chronic myeloid leukemia (3), lymphoma (3), amiloidosis (2) and myelofibrosis (1) – 2 with previous TCTH (for amiloidosis and myelofibrosis). Clinical manifestations in table 1. One patient died (11.1%). Two patients had received chemotherapy in the last 4 weeks. Radiological findings were mainly interstitial (4) and interstitial-alveolar (1). Lymphocytes less than 1000 cel/mm3 were detected in 3 patients; the patient who died had 1000 lymphocytes/mm3. Three patients required ICU; 1 of 2 who required mechanical ventilation died. Time between symptoms onset and start of oseltamivir in table 2; mean therapy length was 6.1 days (3-10 days); 3 days in the case of obit. Prolonged viral shedding was investigated in 3 patients - 1 negative (5 days after first oseltamivir dose) and 2 positive (5 and 7 days after).

Conclusion:
We did not include outpatients because in our country most of the time PCR was available only for those requiring hospitalization, despite of clinical suspicion and oseltamivir prescription. An important challenge recognized was atypical clinical presentation including acute respiratory distress without fever, leading us to consider that we probably lost opportunity to make diagnosis in some other cases. For both reasons, we were not able to know the real impact of H1N1 pandemic infection among onco-hematological patients. We recognize however that, among our hospitalized patients, mortality rate was low as reported recently in hematological cancer patients.

Disclosures:
No relevant conflicts of interest to declare.
Granulocyte Colony-Stimulating Factor Induces High Expression of HLA-G In CD3+CD4+ T Lymphocytes and CD3+CD8+ T Lymphocytes
Authors: Liu Qifa , Chen Yinkui , Wu Xiuli , Du Xuan , Li Rui , Fan Zhiping , Xuan Li , Sun Jing 
Published: October 2019

Abstract
Abstract 4870

Background and objectives:
Human leukocyte antigen –G (HLA–G) is a nonclassic HLA class I molecule and has the immunosuppressive activity. We investigate the effects of Granulocyte colony-stimulating factor (G-CSF) on the expression and secretion level of HLA-G in peripheral blood and bone marrow cells, and attempt to explain the mechanism of the low incidence of graft-versus-host disease (GVHD) in G-CSF-primed bone marrow (G-BM) or peripheral blood stem cells (G-PBSC) transplantation.

Methods:
Bone marrow and peripheral blood cells of 10 donors were collected pre-mobilization and at day 5 after G-CSF mobilization. Flow cytometry was used to detect the expression of membrane-bound HLA-G (mHLA-G) of CD3+CD4+ T lymphocytes, CD3+CD8+ T lymphocytes, CD19+ B lymphocytes, CD56+ NK cell, CD14+ monocytes and CD33+ granulocytes. The levels of soluble HLA-G (sHLA-G) and cytokine were determined by enzyme-linked immunosorbent assay (ELISA). Bone marrow cells and peripheral blood cells of pre-mobilization were incubated for 24h, which are divided into 5 groups: (a) blank group, (b) with G-CSF, (c) with G-CSF and blocking antibody of IL-10, (d) with G-CSF and blocking antibody of IFN-γ, (e) with G-CSF, blocking antibody of IL-10 and blocking antibody of IFN-γ.

Results:
The levels of mHLA-G of CD3+CD4+ lymphocytes, CD3+CD8+ lymphocytes and the levels of sHLA-G at day 5 after G-CSF mobilization groups were significantly higher than the pre-mobilization groups both in bone marrow and peripheral blood cells, especially in CD3+CD8+ lymphocytes. The levels of mHLA-G of CD19+ B lymphocytes, CD56+ NK cells, CD14+ monocytes and CD33+ granulocytes had no significant difference in the two groups. The levels of IL-10 or IFN-γ in plasma of bone marrow or peripheral blood at day 5 after G-CSF mobilization groups were much higher than the pre-mobilization groups. The levels of mHLA-G of CD3+CD4+ lymphocytes, CD3+CD8+ lymphocytes and the levels of sHLA-G in bone marrow cells or peripheral blood cells incubating with G-CSF for 24h were significantly higher than the groups without incubating with G-CSF. And the blocking antibody of IL-10 or the blocking antibody of IFN-γ could not reduce the expression levels of mHLA-G and sHLA-G in vitro.

Conclusion:
G-CSF can act on cells directly to increase the expression levels of HLA-G in CD3+CD4+ T lymphocytes and CD3+CD8+ T lymphocytes. It might be assciated with the low incidence of GVHD in G-BM transplantation or G-PBSC transplantation.
Supported by National Natural Science Foundation of China (30971300), Science and Technology Planning Project of Guangdong Province of China (2009A030200007) and China Postdoctoral Science Foundation (200902332, 20080440776).

Disclosures:
No relevant conflicts of interest to declare.
Dose-Intense BACOP for Treatment of High Risk Peripheral T-Cell NHL (PTCL)
Authors: Aurer Igor , Dujmovic Dino , Radman Ivo , Basic-Kinda Sandra , Nemet Damir , Ilic Ivana , Stern-Padovan Ranka , Santek Fedor , Sertic Dubravka 
Published: October 2019

Abstract
Abstract 4889
PTCLs, except ALK+ ALCL, have a bad prognosis with overall 5-year survival rates below 30%. Because of their relative rarity, no large randomized trials have been performed and the importance of individual cytotoxic agents, their dose density and intensity as well as that of autografting remains unproven. At our center we have been using dose-intense BACOP, a regimen modeled after the French ACVBP, for treatment of patients with high risk PTCL. The regimen consisted of cyclophosphamide 1500 mg/m2 day 1, doxorubicin 75 mg/m2 day 1, bleomycin 15 mg days 1 and 5, vincristine 2 mg days 1 and 5 and prednisone 50 mg/m2 days1-5 every 3 weeks for 4–6 cycles. Responding patients underwent stem-cell collection and autografting after BEAM conditioning. Areas of initially bulky disease and those not in CR prior to transplantation were irradiated posttransplant with 30–40 Gy. Patients with high risk for development of CNS disease received intrathecal methotrexate prophylaxis. Response evaluations were performed after 2–3 cycles and at the end of chemotherapy. Patients were considered high risk if they had any PTCL type with IPI 3 or more, bulky disease or failed to respond to 2–3 cycles of standard CHOP-21. We treated 28 patients, 20 men and 8 women, 17–67 years old (median 46). Thirteen had PTCL-NOS, 8 ALCL, 3 AILD, 2 nasal type, 1 panniculitis-like and 1 hepatosplenic PTCL. Two had stage IE bulky, 1 stage II bulky, 2 stage III and 23 stage IV disease. The toxicity of treatment was substantial, all patients experienced serious hematological toxicity and infections or neutropenic fever, 3 died of infection during chemotherapy and 1 during stem-cell transplantation, 2 had DVT/PE, 1 died of complications related to the necrosis of an extremely bulky tumor and one underwent emergency splenectomy after tumor necrosis caused splenic rupture. Three patients were unavailable for efficacy analysis due to early death, 4 progressed and 21 initially responded (75%); 14 achieved CR and 7 PR. None of the 3 patients with nasal type or hepatosplenic PTCL responded. Of the responders, 11 underwent autografting as intended, 3 relapsed prior to transplantation, treatment was modified in 3 due to toxicity, 2 were not transplanted due to patient refusal or physician decision, 1 underwent allogeneic transplantation and 1 failed to mobilize. After a median follow-up of survivors of 20 months, 9 patients are still alive, including 8 who were autografted as intended. Median response duration was 12 months, FFS 6 months and OS 9 months (Fig). In conclusion, a significant proportion of high-risk PTCL-NOS, ALCL and AILD patients respond to dose-intense BACOP followed by autologous stem-cell transplantation but the toxicity of treatment is substantial.

Disclosures:
No relevant conflicts of interest to declare.
Childhood Anaplastic Large Cell Lymphoma with Unusual Localization-A Case Report
Authors: Unuvar Aysegul , Uzunhan Tugce , Karakas Zeynep , Ozturk Gulyuz , Anak Sema , Agaoglu Leyla , Devecioglu Omer 
Published: October 2019

Abstract
Abstract 4903
Anaplastic large cell lymphoma (ALCL) accounts for approximately 10% of the childhood lymphomas. ALCL is characterized by peripheral, mediastinal or intra-abdominal lymph node involvement or extranodal involvement. We report a child with ALCL with unusual localization. An eleven-year-old boy had been admitted to the another university hospital with left knee pain and swelling for 15 days. The left knee joint punction had been done, and osteomyelitis had been diagnosed, and treated with antibiotics. However, there had been no recovery from his complaints, and left knee synoviectomy had been done. This operation had revealed anaplastic large cell lymphoma in the intraarticular soft tissue of the left knee. Then, he was referred to our hematology and oncology clinic for advanced therapy. There was nothing significant in the background and family history. Physical examination showed a 3 cm mass arising from the left knee joint with lobulated contours. PET-CT showed the left inguinal lymph node involvement, only. Chemotherapy according to ALCL 99 protocol was started because of the tumor was not resectable. After the first course of therapy, tumor mass was reduced apparently. By the end of his second chemotherapy course, tumor was not detectable. Now, he completed his therapy, and he is on follow-up without any complaint or recurrence for 18 months. In conclusion, to the best of our knowledge, this is the first reported case with ALCL originating from the intraarticular soft tissue which was treated successfully.

Disclosures:
No relevant conflicts of interest to declare.
LNA Anti-Microrna-155: a Novel Therapeutic Strategy In Waldenstrom Macroglobulinemia and Chronic Lymphocytic Leukemia
Authors: Zhang Yong , Roccaro Aldo M. , Broom Oliver , Kauppinen Sakari , Liu Yang , Morgan Brittany , Azab Abdel Kareem A. , Azab Feda , Maiso Patricia , Ngo Hai T , Sacco Antonio , Ghobrial Irene M 
Published: October 2019

Abstract
Abstract 4914

Background.
We and others have previously demonstrated that microRNA-155 (miR-155) is overexpressed in patients with Waldenstrom's Macroglobulinemia (WM) and Chronic lymphocytic leukemia (CLL) compared to healthy subjects; indicating that miR-155 may play a crucial role in regulating the pathogenesis of these diseases. We therefore evaluated the role of the novel locked nucleic acid (LNA) antimiR against miR-155 in WM and CLL-derived cell lines.

Methods.
WM and CLL-derived cell lines (BCWM.1, MEC1) have been treated with 20μM antisense LNA antimiR-155 or scramble probe (Santaris Pharma, Hørsholm, Denmark). Efficiency of delivered LNA oligos into cells was determined by using FAM-labeled LNA, followed by Flow cytometry (FACS). Survival and cell proliferation were assessed by MTT assay and thymidine uptake, respectively. Serum levels of miR-155 from peripheral blood of WM patients or healthy subjects and the level of miR-155-targeted genes were detected by quantitative RT-PCR (qPCR).

Results.
Efficiency of delivered LNA oligos into both WM and CLL-derived cell lines was higher than 90%. LNA antimiR-155 reduced proliferation of WM and CLL-derived cell lines, as compared to LNA scramble probe used as a control. In contrast, LNA antimiR-155 did not exert any effect on survival of them. We demonstrated increased expression of miR-155-targeted genes, such as CEBPβ, SOCS1, and TP53DINP1 in WM cells upon LNA antimiR-155 treatment. Moreover, we found miR-155 could be detected in peripheral blood serum of WM patients, but not the serum of healthy subjects.

Summary.
These data provide preclinical evidence for using the novel antisense LNA antimiR-155 in WM and CLL. Moreover, serum levels of miR-155 could potentially be used as a biomarker in patients with WM.

Disclosures:
No relevant conflicts of interest to declare.
Acute Painful Radiculopathy After Intrathecal Rituximab
Authors: Bromberg Jacoline , Doorduyn Jeanette , Baars Johanna W. , Van Imhoff Gustaaf , Enting Roelien , van den Bent Martin 
Published: October 2019

Abstract
Abstract 4920
Within a prospective phase II study (HOVON 80) of patients with recurrent diffuse large B-cel lymphoma in the CNS, three of 13 patients treated with intrathecal rituximab developed an acute, transient, extremely painful lumbosacral radiculopathy. All were treated with systemic R-DHAP every 4 weeks with i.v. HD-MTX on day 15 for three cycles. In addition intrathecal Rituximab was administered twice weekly via lumbar puncture starting on day -1. According to protocol the first administration consisted of 10 mg of rituximab after premedication with acetaminophen, thereafter the dose was increased to 25 mg. No patient experienced side effects of the first intrathecal administration of rituximab. However, after the first administration of 25 mg rituximab three of 13 treated patients reported extremely painful tingling sensations in the buttocks, legs and feet immediately after administration and lasting 30–60 minutes. Concomitantly a temporarily increased bloodpressure was documented. Premedication with an antihistaminic in the third patient was ineffective. No neurologic deficits occurred and the pain resolved completely. The patients refused further treatment with intrathecal rituximab, and therapy was changed to intrathecal methotrexate, without any side effects. After these events the rituximab was diluted in saline to 5 mg/ml, the dose reduced to 10 mg per administration, and 4 mg dexamethasone was administered concomitantly in all subsequent patients. Twelve additional patients were thus treated and no further incidents of painful radiculopathy were observed. This serious, though completely transient, adverse effect of intrathecal rituximab precludes intrathecal administration of higher doses of rituximab via lumbar route. It has never been described after intraventricular administration.

Disclosures:
Bromberg: Roche: Research Funding. Off Label Use: rituximab administration intrathecally. Doorduyn: Roche: Research Funding. van den Bent: Roche: Consultancy, Research Funding.
Triptolide Induces Apoptosis In Acute Lymphoblastic Leukemia Cells by Inhibition of the Oncoprotein MDM2
Authors: Huang Mei , Gu Lubing , Zhou Muxiang 
Published: October 2019

Abstract
Abstract 4934
Triptolide, a nature product derived from the Chinese plant Tripterygium wilfordii, is reported to exhibit antitumor effects in a broad range of cancers. Recent studies indicate that the antitumor activity of triptolide is associated with its biological action to inhibit expression of many oncoproteins and anti-apoptotic or survival factors that were expressed in the cancer cells. Herein, we demonstrate that triptolide induces apoptosis in a subgroup of acute lymphoblastic leukemia (ALL) cells that overexpress MDM2 oncoprotein by inhibiting the MDM2 expression. In pediatric ALL, overexpression of MDM2 by leukemic cells is typically associated with a wild-type (wt) p53 phenotype and resistance to conventional chemotherapeutic drugs such as doxorubicin. In the present study, we evaluated the role of triptolide in regulating MDM2 and in inducing apoptosis, as compared to doxorubicin, using ALL lines and primary ALL samples. In contrast to doxorubicin, which induced p53 activation and a subsequent upregulation of MDM2, triptolide strongly induced persistent inhibition of MDM2 followed by a steady-state activation of p53, which resulted in potent apoptosis of the MDM2-overexpressing ALL cells tested, even if they were doxorubicin-resistant. We discovered that triptolide's inhibition of MDM2 in ALL cells occurred at the post-transcriptional level through inhibition of mRNA synthesis. Because p53 function is inhibited by MDM2 in chemoresistant/MDM2-overexpressing ALL cells, potent killing of these cells by triptolide suggests that this naturally-derived agent may be a novel therapeutic for refractory ALL.

Disclosures:
No relevant conflicts of interest to declare.
Vitamin E Does Not Reduce Cardiomyopathy In Doxorubicin treated Rats
Authors: Guerra Jhon A , Torres-Serrant Maribel , Santiago Pedro J 
Published: October 2019

Abstract
Abstract 4944

Introduction:
The clinical efficacy of doxorubicin is severely limited by its cardiotoxicity. Antioxidants represent the largest class of chemicals examined as potential protective agents and for which there is continuing interest. Dexrazoxane is the current agent used for the control of doxorubicin related cardiotoxicity. However, in large trials the incidence was reduced only by 50% (1). Vitamin E, a known antioxidant and free radical scavenger agent, has been evaluated in the past as a cardio protective drug in animal models receiving doxorubicin but contradictory conclusions regarding this effect have been reported (2, 3). We hypothesized whether Vitamin E has an effect in cardioprotection in rats receiving doxorubicin.

Design and Methods:
Three groups of 6 Rats each were used for the experiment. Group 1 received doxorubicin 1.5mg/kg intraperitoneally (IP) weekly for 9 weeks for a total cumulative dose of 13.5mg/kg. Group 2 received Vitamin E 100 IU/kg/weekly by IP injection, 48 hours prior to the doxorubicin. Group 3 received 0.5 cc of saline solution 0.9% IP weekly for 9 weeks as control group. Functional parameters including plasmatic nitric oxide (NO) levels and cardiac ejection fraction (EF) were determined on each group at the end of the experiment.

Results:
Doxorubicin treatment significantly increased plasmatic NO concentration when compared with controls (35.30 ± 5.63 mM vs. 14.72 ± 2.66 mM, n=6, P=0.016); however, in the group of rats receiving Vitamin E prior to doxorubicin, NO did not have a significant decrease (from 35.30 ± 5.63 mM to 31.77± 8.91 mM n=6, P=0.75). Regarding EF, doxorubicin treatment decreased EF significantly when compared with saline controls rats (59 ± 5.61% vs. 77 ± 3.89 %, n=6, P<0.05); however, in the group of rats receiving Vitamin E prior to doxorubicin, EF did not have a significant improvement (from 59 ± 5.61% to 69.17 ± 4.4, n=6, P=0.24).

Conclusion:
These results suggest that Vitamin E does not prevent or reduce cardiac injury in rats treated with doxorubicin. Different alternatives including other antioxidants could be explored in an attempt to decrease cardiotoxicity produced by doxorubicin and to improve the effect of the standard cardioprotective agent used Dexrazoxane. Further studies are necessary.
References:
1. Swain SM. Adult multicenter trials using dexrazoxane to protect against cardiac toxicity. Semin Onco 1998; 25 (4 Suppl 10):43-7
2. Breed JG, Zimmerman AN, Dormans JA, Pinedo HM. Failure of the antioxidant vitamin E to protect against adriamycin-induced cardiotoxicity in the rabbit. Cancer Res 1980; 40:2033-8
3. Myers CE, McGuire W, Young R. Adriamycin: amelioration of toxicity by alpha-tocopherol. Cancer Treat Rep 1976; 60:961-2

Disclosures:
No relevant conflicts of interest to declare.