bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation between Angiogenic and Coagulation-Fibrinolysis Factors and Stage of Disease in Non Hodgkin’s Lymphoma Patients.
Authors: Mazur Grzegorz , Poreba Malgorzata , Wrobel Tomasz , Poreba Rafal , Pyszel Angelika , Beck Boguslaw , Steinmetz-Beck Aleksandra , Andrzejak Ryszard , Kuliczkowski Kazimierz 
Published: October 2019

Abstract
BACKGROUND: Angiogenesis and activation of coagulation system in cancer patients are common and are thought to be unfavorable clinical parameters. Vascular endothelial growth factor (VEGF) and fibroblast growth factor (bFGF) are well-known angiogenic cytokines. The elevations of plasma fibrinogen and D-dimer level indicate coagulation and fibrinolysis activation. There may be links between angiogenic cytokines and coagulation - fibrinolysis factors in cancer. Possible specific interactions include releasing angiogenic factors, such as VEGF by activated platelets and binding of VEGF and bFGF to fibrin and fibrinogen resulting in an increase in endothelial cell proliferation.
AIM: The purpose of our study was: (a) to analyze relations of VEGF, bFGF serum levels and fibrinogen, D-dimer plasma levels with stage of disease according to Ann Arbor Staging System (AASS); (b) to evaluate correlation between serum levels of angiogenic cytokines and plasma levels of coagulation-fibrinolysis factors in non Hodgkin’s lymphoma patients.
MATERIAL AND METHODS: 52 non Hodgkin’s lymphoma patients (31 men, 21 women; median age 52,1 ± 14,7 years) in II, III or IV stage of disease according to AASS were assessed. In stage II were 15, in stage III- 10 and in stage IV- 27 persons. Serum VEGF, bFGF and plasma D-dimer levels were measured by enzyme-linked immunosorbent assay (ELISA). Plasma levels of fibrinogen were determined using Behring Coagulation System (BCS) equipment.
RESULTS: Plasma level of D-dimer was elevated in majority of patients, mean plasma D-dimer levels [ng/ml] were in stage II: 1654,3 ± 1301,5, in stage III: 1816,6 ± 1370,7, in stage IV: 2747,1 ± 1410,8. There was significantly higher D-dimer level in IV stage of disease in comparison to stage II and III. p<0,01. The mean serum VEGF levels [pg/mL] in following stages of disease were: in II: 387,4 ± 219,8, in III: 399,2 ± 235,0, in IV: 406,9 ± 308,8; mean serum bFGF levels [pg/mL] were: in II: 4,3 ± 2,9, in III: 4,6 ± 2,5, in IV: 4,4 ± 3,4; mean plasma fibrinogen levels [mg%] were: in II: 514,3 ± 198,7, in III: 518,0 ± 209,2, in IV: 495,4 ± 155,3). Differences in levels of VEGF, bFGF and fibrinogen between II, III and IV stage of disease were not statistically significant We observed positive linear correlation between VEGF and fibrinogen (r = 0,45; p<0,01) and between bFGF and fibrinogen (r = 0,52; p<0,05) and negative linear correlation between VEGF and D-dimer (r = −0,69; p<0,001) and between bFGF and D-dimer (r = −0,72; p<0,001).
CONCLUSIONS: Our study indicates that D-dimer level correlates with Ann Arbor Staging System in non Hodgkin’s lymphoma patients. Significant correlations between levels of VEGF/bFGF and fibrinogen/D-dimer suggest specific interactions between angiogenic and coagulation-fibrinolysis system.
Evidence for Disease Specific Immunophenotypic Abnormalities in Blood from Patients with Mantle Cell Lymphoma.
Authors: Narvaez Amy B. , Gascon Ronnie L. , Zhang Rongzhen , Kaplan Lawrence , McGrath Michael S. 
Published: October 2019

Abstract
Immune dysfunction is known to contribute to lymphomagenesis in the context of immunosuppressive therapy and infection with HIV. The current study was undertaken to test whether low grade but progressive forms of lymphoma, mantle cell lymphoma (MCL) and follicular lymphoma (FL), might be associated with systemic immunologic dysfunction as evaluated by flow cytometry. Because of recent studies suggesting a tumor initiating function for infiltrating macrophages in AIDS lymphoma (Zenger et al, Cancer Research62:5536–42,2002), we investigated the immunophenotype of both monocytes and T cells in blood from patients with recurrent MCL and FL. Heparinized blood was taken from 13 individuals with MCL and 6 with FL, both sets of patients previously treated with an average of 4 cycles of combination chemotherapy +/− Rituxan. No patient had received any therapy during the 3 months prior to the current study. Cell surface antigens CD14, CD16, HLA-DR, CD4, CD8, and CD38 were studied in the two diseases and results were compared to age matched controls. Blood from MCL patients showed an immunophenotypic pattern, similar to blood phenotypes described for patients infected with HIV. The %CD4 population was significantly lower than normal controls (p<0.05). The %CD8 T-cell population was elevated when compared to normal (p<0.001) as was the median level of CD38 expression on CD8 T-cells (p<0.01). The CD4/CD8 ratio was inverted (<0.85). Significant elevation of monocyte activation markers was observed in MCL blood when compared to normal controls. Mean fluorescence of HLA-DR on CD14+ cells was elevated (p<0.0001) as was the %CD14+ cells co-expressing CD16 (p<0.0003). By comparison, FL blood showed evidence for both CD4 and CD8 T cell activation with normal CD4/CD8 ratios, however there was no evidence for CD14 cell activation as observed in MCL blood. Taken together, these data suggest that MCL, as a lymphoma subset, shows significant evidence for systemic immune dysfunction and as an acknowledged T cell independent process, shows evidence for macrophage activation, shown recently to potentially play a role in AIDS lymphomagenesis. Further studies on MCL will be required to determine what “factors” might contribute to the persistently abnormal immunophenotype including investigating this class of lymphoma for viral like factors.
Relationship between Seroresponse to Epstein-Barr Virus and Survival in Patients with Lymphoid Malignancies.
Authors: Domingo-Domenech E. , Middeldorp J. , Gonzalez-Barca E. , Benavente Y. , Romagosa V. , Font R. , de Sevilla A. Fernandez , Meijer C. J. , de Sanjose S. 
Published: October 2019

Abstract
Introduction: Epstein-Barr virus (EBV) infection is a common life event that has been consistently associated to several lymphoproliferative malignancies. It is unclear to what extent EBV can be associated to clinical presentation and outcome of lymphomas.
Objectives: To evaluate the association between the seroresponse to EBV with the clinical presentation and survival in the different lymphoid malignancies.
Methods: As part of the EPILYMPH_Spain case-control study, 414 newly diagnosed lymphoma cases and 488 controls, age and sex matched to the cases, were systematically recruited in a single center during 20 months (starting in 1998). From all subjects, a blood sample was drawn at diagnosis and EBV serostatus was evaluated through ELISA assays to measure IgG reactivity against immunodominant epitopes of EBNA1(BKRF1) and VCA-p18 (BFRF3). Further, immunoblot analysis was performed to evaluate distinct antibody patterns to EBNA1, VCA18, VCA-p40 (BdRF1) and Zebra (BZLF1). These patterns were classified into two groups: reactive (with wide responsiveness to the different EBV proteins) and non-reactive (with an IgG reactivity restricted to a limited number of EBV proteins). Statistical differences between each group were analyzed using Chi-square test for categorical data and T-Student test for continuous data. Survival analysis was performed by Kaplan-Meier techniques and compared with the log rang test. Values of p<0.05 were considered to be statistically significant. All data were adjusted for age and sex.
Results: Twenty-four percent (101/414) of the cases and 17% (86/488) of the controls had an EBV reactive response pattern (p= 0.012). Among cases, 29% females versus 20% of males presented an EBV reactive pattern (p= 0.031), with no differences regarding median age. When we agrupated the different lymphoid malignancies into the 3 most important entities, differences in the prevalence of EBV seropositivity were found: B-cell neoplasms (25%), Hodgkin lymphomas (12%) and T-cell neoplasms (34%), p=0.05. When analyzing the different WHO entities, in myeloma patients, EBV reactive pattern was found to be associated to an early stage disease (29% Stage 1 vs 5% Stage 2–3; p= 0.038) and a longer median survival (not reached vs 38 months; p= 0.02).
Conclusions: EBV seroprevalence is higher in lymphoma patients, with a slight predominance in females. EBV reactive pattern seems to be associated to early stage myeloma, which implicates a better survival.
FDG-PET Demonstrates Different Metabolic Activities among Lymphoma Subtypes.
Authors: Kostakoglu Lale , Goldsmith Stanley J. , Chandramouly Anjaly , Vidan Erez , Verma Sumeet , Coleman Morton 
Published: October 2019

Abstract
Lymphomas may often present with more than one pathologic type in the same individual. This study assesses the variability of FDG uptake values as determined by SUV’s in various lymphoma subtypes to serve as a platform for differentiating and confirming the pathologic diagnosis in all disease sites.
Methods: We retrospectively evaluated the PET-CT studies of 184 lymphoma patients at initial staging or at relapse prior to therapy. Lymphoma subtypes were classified according to the WHO classification. SUV’s were obtained in a total of 1120 nodal or extranodal disease sites in 11 lymphoma subtypes. Mean SUV’s were calculated for each lymphoma subtype by dividing the total maximum SUV’s by the number of disease sites in all patients. Consequently, mean SUV +/− SD and SUV range were determined and correlated with histologic diagnosis as shown in the Table.
Results: Results are summarized in Table 1. The highest mean SUV’s were obtained in aggressive non-Hodgkin’s lymphomas (NHL) followed by Hodgkin’s disease (HD) and indolent NHL. Starting from the subtype with the highest mean SUV of the means and in a rank of decreasing order, the subtypes of lymphoma are as follows; Burkitts, DLCL, T cell rich B cell, natural killer T cell, HD, Anaplastic T-cell, mantle cell, marginal zone, follicular, T cell peripheral and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).
Conclusions: While SUV’s may be quite variable, a general pattern does exist for each lymphoma subtype. A major discrepancy between the SUV’s and histologic diagnosis should be assessed by repeat biopsy.
SUV Distribution Among Subtypes of Lymphoma* Type of Lymphoma Patient Number Mean+/−SD Range *Table does not cover all lymphoma subtypes studied in this study due to limited space, HD: Hodgkins Disease NHL: Non Hodgkins lymphoma, DLCL: Diffuse large cell lymphoma, CLL/SLL: Chronic lymphocytic leukemia/small lymphocytic lymphoma HD 45 7.5+/−3.7 2–22 Mantle cell 8 6.8+/−4.9 2.1–21 DLCL 58 11.3+/−7.3 2.2–58 T cell Rich B cell 5 9.1+/−5.5 4–25 Burkitts 9 11.8+/−10.5 2–44 Follicular 30 5.1+/−2.7 1.6–11 CLL/SLL 11 3.0+/−1.5 1.1–8.8 Marginal Zone 10 5.5+/−3.8 2.1–21
Angioimmunoblastic T- Cell Lymphoma by Flow Cytometric Analysis.
Authors: Agarwal Ashima , Fisher Stephen I. 
Published: October 2019

Abstract
Background: Angioimmunoblastic T cell lymphoma (AILT) is a peripheral T- cell lymphoma characterized by systemic disease, a polymorphous infiltrate involving lymph nodes with prominent proliferation of high endothelial venules and follicular dendritic cells. We present a novel technique for the presumptive diagnosis of AILT cases by flow cytometric analysis. The diagnosis of AILT was confirmed by histolopathologic features, immunohistochemical stains and molecular studies.
Method: Specimens: Fresh groin excision lymph nodes. Flow cytometric analysis utilizing side scatter versus CD45. Case 1 (figure 1): The gated population consists of 10–12% B cells and 56–61% T cells. CD3, CD4 and CD5 stain 56–61% of the gated cells, while CD7 stains 41% of the gated cells, consistent with aberrant partial loss of CD7 by T cells. A population of abnormal T cells expresses CD10 with CD2, CD3, CD4 and CD7 but not with CD19 (B cells) consistent with aberrant CD10 coexpression by a subset of the T cells (12–19% of the gated cells). Staining for CD34 highlights less than 2% immature cells staining while CD64 stains less than 2% monocytic cells. Surface kappa and lambda staining does not show restriction (kappa: lambda 1–2:1). Cytoplasmic kappa and lambda staining is not interpretable due to non-specific antibody binding. Case 2 (figure 2): The gated population consists of 69% T- cells and 28–33% B- cells. A population of abnormal T cells expresses CD10 with CD2, CD3, CD4 and CD7 but not CD19 consistent with aberrant CD10 expression by a subpopulation of T cells (8–11% of gated cells). Intracellular B cell kappa lambda light chain restriction is not present and there is no aberrant co-expression of CD5, CD10 or CD43 by B cells. The diagnosis of AILT was confirmed by standard morphologic, immunoperoxidase and molecular methods subsequently in both of these cases.
Discussion: Aberrant CD10 expression on neoplastic T cells has been shown with immunohistochemical staining of paraffin embedded tissue in AILT. Our cases show aberrant coexpression of CD10 by CD2, CD3, CD4 and CD7 positive T cells in more than 10% of gated cells by Flow cytometric analysis.
Conclusion: Flow Cytometric analysis is a useful and reproducible tool for immunophenotyping AILT cells and should be considered for presumptive diagnosis of AILT.
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Excellent Stem Cell Mobilization Using Escalated BEACOPP in High-Risk Patients with Hodgkin’s Disease.
Authors: Kandler Gabriele , Fillitz Michael , Moestl Michaela , Schloegl Ernst , Reisner Regina , Pittermann-Hoecker Elisabeth , Noesslinger Thomas , Pfeilstoecker Michael 
Published: October 2019

Abstract
Introduction: After intensive treatment regimens have been established, the survival rate for patients with advanced Hodgkin’s disease is approximately 91 % after five years and 13 % of the patients have a relapse or have primary progressive disease (2 %) within the first five years. For patients with relapse after conventional chemotherapy +/− radiotherapy, however, there is a real chance of achieving remission again. Since it is often difficult to harvest autologous stem cells following an intensive pretreatment, our center embarks on the strategy to harvest autologous blood stem cells in high-risk patients, defined according to the risk stratification of the German Hodgkin Study Group, already as part of the initial polychemotherapy.
Results: Between 9/2003 and 5/2005, we analyzed the results of the stem cell harvest of 12 consecutive patients with Hodgkin’s disease who were mobilized with the escalated BEACOPP regimen. There were 7 female and 5 male patients. Escalated BEACOPP was the primary therapy in ten patients and a relapse was treated in two patients; the previous treatment was 4 or 6 cycles of the ABVD regime + involved field radiation. The ten patients who did not receive previous treatment were classified as having Ann Arbor stage IIA/2 IIB/5, IIIB/2 and IVB/1 and all of them had a large mediastinal bulk as an additional risk factor. The two patients who did receive a previous treatment were classified as having an initial Ann Arbor stage IIA or IIB, without an additional risk factor. The stem cells were collected in 1 patient from cycle 2, in 8 patients from cycle 3 and in 3 patients from cycle 4 of the escalated BEACOPP regimen. A total of 11 patients received a standard dose of filgrastim, 5μg/kg body weight s.c., from day 8 up to the last apheresis and 1 patient received pegfilgrastim 6mg s.c. All aphereses were performed using an Amicus cell separator® (Baxter, MNC set, closed two-arm). 7 patients required only 1 apheresis and the remaining 5 patients required 2 aphereses. An apheresis result sufficient for a possible reinfusion could be achieved in all patients (4.26 – 14.4 x10e6 CD34 pos. cells/kg/body weight, mean: 7.7).
Summary: According to our experience, escalated BEACOPP regimen is very suitable for the harvesting of stem cells in high-risk patients with Hodgkin’s disease even though they are receiving procarbazine. A sufficient quantity of stem cells can also be collected from pretreated patients. The stem cell mobilization can be integrated into the escalated BEACOPP regimen safely and without a delay in treatment and thus creates, already at an early stage, the pre-condition for a high-dose therapy, which might be required in high-risk patients.
Study of Pegylated Liposomal Doxorubicin in First Line Therapy of Aggressive Lymphomas.
Authors: Mandala Eudokia , Lafaras Christos , Ilonidis George , Venizelos Ioannis , Grollios George , Tsioni Constantina , Bischiniotis Theodoros , Arvanitakis Constantinos 
Published: October 2019

Abstract
Purpose: Conventional doxorubicin is currently used in many treatment protocols for lymphoma. Pegylated liposomal doxorubicin has a different pharmacokinetic profile with prolonged half life, reduced toxicity, especially cardiotoxicity and possible enhanced antitumor activity. This study was designed to evaluate tolerability and efficacy of pegylated liposomal doxorubicin in patients with aggressive lymphomas.
Methods: Twenty-nine patients entered the study, 12 male, aged 36–86 (median 66 years), 22 with newly diagnosed CD20 positive diffuse large B-cell lymphoma (DLBCL), elderly with median age 77 years, 4 MALT in transformation, 2 mantle and one anaplastic. Patients’ characteristics: IPI-1 10%, IPI-2 25%, IPI-3 10%, IPI-4 55%, stages III–IV 60%, bulky disease 40%, extranodal 55%. Combined immunochemotherapy with Rituximab 375 mg/m2, day1, added to standard CHOP was performed, 8 courses, with a follow up of nearly 3 years. Pegylated liposomal doxorubicin (Caelyx®) replaced doxorubicin at 30 mg/m2. Response was evaluated after 3 and 8 courses. Cardiac function was estimated at the beginning and after the end of therapy. LVEF, fractional shortening (FS) and myocardial performance index (MPI) according Tei et al, as most sensitive index for global LV function, were measured.
Results: All responded except for three, one with active SEL and one with CNS lymphoma (refractory 10%). Overall response 91%, CR 76%, PR 15%, overall survival 82%, relapse rate 4.5% (1/22). No synergistic toxicity was observed, as there were no remarkable hematological or extrahematological toxic events. No clinical deterioration of cardiac function was observed. The patient with anaplastic lymphoma had severe preexisting cardiovascular disease and died from cardiac complications, in lymphoma remission. Two patients experienced a single episode of atrial fibrillation with successful pharmaceutical conversion. None developed alopecia, nausea, vomiting, palmar-plantar erythrodysesthesia, local injury in extravasation area. Treatment related mortality was documented in none. LVEF and FS were not changed, but MPI was slightly increased, detecting subclinical myocardial dysfunction.
Conclusions: Pegylated liposomal doxorubicin is useful in the treatment of aggressive lymphomas, including elderly patients, well tolerated, producing durable complete remissions and offering advantages in combination with immunotherapy.
Membrane Derived Micorvesicles - Underappreciated Components of the Tumor Microenvironment That Modulate Tumor Growth, Vascularization and Metastasis.
Authors: Wysoczynski Marcin , Hayek Fadhi , Ratajczak Janina , Janowska-Wieczorek Anna , Ratajczak Mariusz Z. 
Published: October 2019

Abstract
Viable eukaryotic cells shed circular membrane fragments called microvesicles (MV) from the cell surface and secrete them from the endosomal compartments. These MV, which are different from apoptotic bodies, are enriched in lipids, proteins and mRNA. We postulate that MV play an important and underappreciated role in cell-cell communication by i) stimulating target cells with ligands that the MV express, ii) fusing with target cells and thus transferring various receptors to their surface, and iii) delivering mRNA, lipids and proteins. Since tumor cells secrete large quantities of MV we hypothesized that the latter are important constituents of the tumor microenvironment and their role in tumor progression merited investigation. First, we observed that human and murine lung cancer cell lines secrete more MV in response to non-apoptotic doses of hypoxia, irradiation and chemotherapy. The MV derived from human cancer cells chemoattracted bone marrow-, lymph node- and lung-derived fibroblasts and endothelial cells and activated in these stromal cells the phosphorylation of MAPKp42/44 and AKT. Furthermore, they also induced in bone marrow- and lung-derived fibroblasts expression of LIF, OSM, IL-11, VEGF and MMP-9. Moreover, conditioned media from marrow fibroblasts exposed to MV induced phosphorylation of STAT-3 proteins and chemoattracted lung cancer cells in a LIF- and OSM-dependent manner and, together with IL-11 and VEGF, activated osteoclasts and endothelial cells. Furthermore, MV from cancer cells embedded in Matrigel implants strongly stimulated angiogenesis. We also found that tumor-derived MV express tissue factor (TF) and activate platelets and as a result of this MV derived from activated platelets transfer several adhesion molecules from platelets to the tumor cell surface. This increases adhesiveness of lung cancer cells in endothelium and their metastatic spread in vivo after injection into syngeneic mice. Finally, we found that formation of MV depends on the formation of membrane lipid rafts. Thus we postulate that tumor- and platelet-derived MV are underappreciated constituents of the tumor microenvironment and play a pivotal role in tumor progression/metastasis and angiogenesis. As MV formation appears to be lipid raft-dependent, we suggest that inhibitors of membrane lipid raft formation (e.g, statins or polyene antibiotics) could decrease MV-dependent tumor spread/growth and we are currently testing this hypothesis in animal models in vivo.