bluuebunny/crossref_metadata_2025_split huggingface dataset:
4g/5g Prevalence in 223 Patients with Thrombosis and in 162 Healthy Controls, from the Centre Region of Portugal.
Authors: Maia Rosa , Cortesao Emilia , Geraldes Catarina , Simoes Luis , Simoes Carla , Castro Graca , Anacleto Gabriel , Barbosa Vieira , Teixeira Adriana 
Published: October 2019

Abstract
A deletion/insertion polymorphism (4G or 5G) in the promoter of the PAI-1 gene has been suggested to be involved in regulation of the synthesis of the inhibitor, the 4G allele being associated with enhanced gene expression, and therefore related with thrombosis. In the present work we studied the prevalence of 4G/5G polymorphism in 223 unrelated patients with history of objectively confirmed thromboembolism, and in 162 healthy unrelated controls, both groups natural from all centre regions of Portugal. In this normal cohort, the prevalence of 4G/4G is 23%, 4G/5G is 38% and 5G/5G is 39%; in the affected population is, respectively, 47%, 21.5% and 30%, which means that 4G/4G is twice more frequent in the patients with thrombosis. When we relate the age of the first thrombosis episodes in the three groups, we find no significative difference, as the respective media is 36.8; 38.6 and 35.5 years in the 4G/4G, 4G/5G and 5G/5G group, respectively. This data suggest that this polymorphism by itself, even in homozygosity, is not associated with earlier thrombosis. In our patients, we studied the presence of Lupus Anticoagulant, Factor V Leiden, Factor IIG20210A, MTHFR C677T, and also Antithrombin III, Protein S and Protein C levels. We analyse the prevalence of the three mutations in patients with DVP, PTE, ischemic and venous CVA and we only find a significative difference in the 4G/4G group: 46.2% patients with DVP and 48.2% patients with PTE (23% in normal cohort). In conclusion, in the centre region of Portugal, the prevalence of 4G/4G is 23%, 4G/5G is 38% and 5G/5G is 39%; in our cohort of unrelated patients the only significative difference is in the 4G/4G group (47%); this variation maintain in the DVP and PTE group. We did not find difference at the age of the first thrombotic episode, in the three groups.
Management of Anticoagulation in Patients Who Requiere Colonoscopy or Gastroscopy: Safety and Efficacy of Sodic Bemiparin (Hibor®.
Authors: Santamaria Maria Amparo , Mateo Jose , Pujol Nuria , Souto Juan C. , Constans Mireia , Ortin Rosa , Llobet Dolores , Fontcuberta Jordi 
Published: October 2019

Abstract
Introduction
Nowadays, most patients under oral anticoagulation treatment (OAT) require invasive procedures such as colonoscopy or gastroscopy. The goals of the management OF OAT are to minimize the risk of thromboembolism and bleeding. Few studies have analyzed the efficacy and safety of low-molecular-weight-heparin (LMWH) in the periprocedure management. We have performed a prospective, observational study to evaluate these parameters using high-dose thromboprophylactic therapy with sodic Bemiparin. (Hibor ®)
Methods
From January 2004 since June 2004, patients under OCT were included before colonoscopy or gastroscopy procedures. Periprocedure prophylaxis consisted on: Acenocoumarol patients: Day -3: withdrawal acenocumarol. Days -2,-1,0: Hibor ®3500 UI/d sc and days +1,+2,+3: Hibor ®3500 U/I + acenocumarol. And day +5: acenocumarol only. Warfarin patients: Días -5,-4: withdrawal warfarin, −3, −2, −1, 0; Hibor ® 3500 UI/d sc, days +1,+2,+3,+4: Hibor ®3500 UI/d sc and warfarin and day +5; warfarin only. Thromboembolic complications and bleeding were recorded in a 3 months follow-up.
Results.
We included 65 patients, 33 women and 32 men. Mean age of women was 72 (range: 50–87) years-old and 72 (range: 39–86) in men. 53 were taken acenocoumarol, and 12 warfarin. OAT indications were: 9 prosthethic mechanical mitral valves 12 prosthetic mechanical aortic valves, 4 with mechanical mitral and aortic replacement, 7 with thrombophilia, 7 with embolic atrial fibrilation/flutter (AF) 18 with isolated AF,1 ischemic cardiomyopathy (IM), 3 with IM and AF and 5 with mitral valvulopathy. 24 gastroscopies and 41 colonoscopies were performed. Mean follow-up was 3 months.
No thromboembolic complications were observed. Only one episode of minor bleeding no related with Bemiparin thromboembolic therapy was recorded. One patient developed pruritus at the punction site. No heparin-related thrombopenia cases were observed.
ConclusionsHigh-dose thromboprophilactic therapy with Bemiparin (Hibor ®) is a safe and effective in periprocedures management in patients under OAT who require gastroscopy or colonoscopy
Role of Protein Kinase C in Expression of Granulocyte Colony Stimulating Factor and Granulocyte-Macrophage Colony Stimulating Factor in Lung Cancer Cells.
Authors: Uemura Yoshiki , Kobayashi Makoto , Nakata Hideshi , Kubota Tetsuya , Taguchi Hirokuni 
Published: October 2019

Abstract
Many cases of tumors that produce granulocyte-colony stimulating factor (G-CSF) or granulocyte macrophage-colony stimulating factor (GM-CSF) have been reported. However, the biological properties regulatory mechanisms of the overproduction of G-CSFor GM-CSF by tumor cells are not well known. We present the role of protein kinase C (PKC) pathways in the constitutive expression of G-CSF and GM-CSF by lung cancer cells. We previously established two lung cancer cell lines, OKa-C-1 and MI-4, that constitutively produce an abundant dose of G-CSF and GM-CSF. We showed that the PKC activator; phorbol 12-myristate 13-acetate (PMA) stimulated the production of GM-CSF in a dose-dependent manner and inversely reduced G-CSF in the cell lines. These effects of PMA were antagonized by PKC inhibitor; staurosporine. The induction of GM-CSF expression by PMA was mediated through the activations of nuclear factor (NF)-kB activation. The induction of G-CSF expression by staurosporine was mediated through p44/42 mitogen-activated protein kinase (MAPK) pathway signaling. PMA accelerated cell growth and inhibited cell death in the cell line. Whereas staurosporine acted inversely. GM-CSF induced by PMA might stimulate cell growth and suppress cell death. G-CSF expression by staurosporine appears to be related to the activation of p44/42 MAPK, and GM-CSF by PMA to NF-kB in OKa-C-1 and MI-4 cells.
Figure Figure
Gene Expression of Insulin-Like Growth Factor Binding Proteins (IGFBP-2 and IGFBP-3) in Childhood Acute Myeloblastic Leukemia. Intr. by Herbert Sayer.
Authors: Dawczynski Kristin , Gruhn Bernd , Pfaffendorf Nadine , Susan Wittig , Voigt Astrit , Steinbach Daniel , Zintl Felix 
Published: October 2019

Abstract
Insulin-like growth factor (IGF) system plays an important role in regulating cellular proliferation. Alterations to the Insulin-like growth factor system have been reported for different tumors. They are of particular interest in the search for new prognostic and therapeutic approaches to cancer treatment. This study aimed to investigate the expression of IGFBP-2, IGFBP-3, IGF-I and IGF-II genes in leukemic cells from children with previously untreated acute myeloblastic leukemia (AML).The expression of IGF-I and IGF-II genes as well as IGFBP-2 and IGFBP-3 genes were measured using TaqMan real-time PCR in 50 children (mean age 10.8±4.8 years). All four genes were expressed with a great variability. RNA samples were extracted from leukemic cells enriched by Ficoll-Hypaque density gradient separation of bone marrow or peripheral blood mononuclear cells (MNC). MNC samples from peripheral blood and bone marrow of healthy children were used as controls. The median expression of IGFBP-2 was 25 times higher in AML cells than in peripheral MNC (p<0.001) and 10 times higher in bone marrow of healthy children (p<0.01). Increased IGFBP-2 gene expression at time of diagnosis was associated with a poor prognosis and a shortened survival time. Leukemic cells of patients who remained in continuous complete remission during the follow up showed a significant decreased IGFBP-2 gene expression at time of diagnosis compared to patients who suffered from relapse (p=0.05).On the other hand, AML cells showed a significantly lower IGFBP-3 gene expression than controls. The median expression of IGFBP-3 was 30 times lower in AML cells than in peripheral MNC (p<0.001) and 20 times lower than in bone marrow of healthy children (p<0.001). No significant difference could be found in IGF-I and IGF-II expression between leukemic and normal cells. Leukemic cells from children with previously untreated AML express components of IGF system. Especially IGFBP-2 seems to play an important role. By this mechanism, IGFBP-2 promotes their own growth in an autocrine, paracrine or endocrine manner. Whether these components will be useful as prognostic factors in stratification of AML treatment in children needs to be evaluated.
Overexpression of Jak Kinases Promotes In Vitro Transformation.
Authors: Knoops Laurent , Royer Yohan , Constantinescu Stefan , Renauld Jean-Christophe 
Published: October 2019

Abstract
The Jak-STAT pathway is responsible for signal transduction by a large number of cytokine receptors. While this pathway is normally tightly regulated, constitutive STAT3 and STAT5 activation is frequent in hematologic malignancies and contributes to oncogenesis. We took advantage of the IL-3-dependent pro-B Ba/F3 cell line to analyze the mechanisms of constitutive STAT activation in vitro. Ba/F3 cells transfected with a mutated hIL-9R (Ba/F3 Phe116) poorly respond to IL-9. However, after selection with this cytokine, we obtained cell lines that proliferated well in IL-9. After cytokine withdrawal, those cells, in contrast to the parental cells, gave rise to autonomous Ba/F3 cell lines showing constitutive STAT5 activation, and that were highly tumorigenic in vivo. This process mimics the multistep process of oncogenesis occurring in vivo. To dissect the mechanisms involved in this cellular transformation, we analyzed, using cDNA microarrays, genes expressed in one of these autonomous lines. Jak1, the Jak kinase associated to the IL-9 receptor, was found to be upregulated compared to parental cells. It was the key genetic event involved in this transformation since ectopic Jak1 overexpression increased the sensitivity to IL-9 and allowed, after a second selection step, for spontaneous progression towards autonomous cell lines with constitutive STAT activation. Using Jak1 mutants, we showed that the generation of autonomous lines was dependent on the tyrosine kinase activity of Jak1 and on a functional FERM domain, the domain that mediates association with the receptor. These results were extended to the other Jak family members. Therefore, we propose that Jak overexpression can be considered as one of the oncogenic events leading to the selection of cells highly responsive to growth factors and, after a second selection step, to autonomous cells with constitutive activation of the Jak-STAT pathway. This process could be extended to human malignancies and might explain, for instance, the constitutive STAT6 activation in primary mediastinal large B cell lymphomas where Jak2 overexpression was described.
Application of Risk-Adapted Therapy for Acute Myeloid Leukemia to a Population. Effects of Stem Cell Transplantation on Outcome.
Authors: Wahlin Anders , Brune Mats L. , Billstrom Rolf 
Published: October 2019

Abstract
We introduced a risk-adapted treatment program for non-APL AML in four Swedish health regions. The aim was to optimise treatment results by the use of risk group stratification, mainly based on cytogenetic findings at diagnosis. All patients received induction therapy with idarubicin-cytarabine 3+7 and consolidation cycles containing high-dose cytarabine. Stem cell transplantation was done in CR1 in selected patients, sparing patients with low/intermediate risk of relapse the risks associated with transplantation. 279 patients, 77% of all AML patients 18–60 years (median 51 yrs), in the population were included in the program. Cytogenetics was performed in 98%. Excluding APL, 19 patients had low-risk. The intermediate-risk group consisted of 165 patients, 96 with a normal karyotype. 95 patients were allocated to the high-risk group. 6% died < 30 days after diagnosis. CR rate was 80%. 111 transplants, 78 allogeneic/URD and 33 autologous, were performed in CR1. 40% of all patients were alive after five years. Median overall survival time was 887 days in low-risk, 611 days in intermediate risk, 345 days in high-risk patients. Relapse-free survival times were also significantly (p<0.001) different between the three risk groups. 43% of responding patients were alive in first remission after four years. 4-year relapse-free survival was significantly better for both intermediate risk (67%) and high-risk (41%) with allogeneic/URD transplantation than with autologous transplant or chemotherapy alone. Relapse was observed more often among patients treated with chemotherapy alone (42%, p=0.03) or with autologous transplants (42%, p=0.09) than among patients receiving allogeneic/URD transplants in CR1, 22%. Our results do not support the use of autologous transplantation in AML in first remission.
A Study of the Toxicity of Gemtuzumab Ozogamicin in Primary and Relapsed AML, Administered Alone or Simultaneously with Intensive Chemotherapy.
Authors: Larsen Thomas Stauffer , Schmidt Kai G. 
Published: October 2019

Abstract
Introduction: Gemtuzumab Ozogamicin (Mylotarg®) is a humanized anti CD33 antibody linked to the cytotoxic drug calicheamicin, which has shown considerable antileukaemic effect in the treatment of relapsed AML. With special regard to its toxicity, we present our preliminary results of Mylotarg treatment when administered on compassionate basis as consolidating monotherapy, or combined with intensive chemotherapy.
Patients and methods: A total of 86 doses, corresponding to 65 courses were administered to 49 patients. Indications for Mylotarg treatment ( mono ~ monotherapy; comb ~ combination therapy. No.of courses are shown in parentheses): Primary AML: Reinduction ( mono:1; comb:3). Cytogenetic reinduction ( mono:3; comb:1). Consolidation ( mono:24; comb:2). Relapsed AML: Induction ( mono:4; comb:11). Reinduction ( mono:1; comb:2). Cytogenetic reinduction ( mono:1). Consolidation ( mono:10; comb:2).
Results: Up-front consolidation with Mylotarg as monotherapy ( 30 doses; 24 patients; mean Mylotarg dose 5.7 mg/m2). Fever: 51% of doses. Focal infections: 17%. Bacteremia 7%. Biochemical findings: Platelet nadir at day 10 ( < 20 bill./l: 25% doses). Neutrophil nadir at day 11 ( mean count = 0.12 bill./l). Hepatic toxicity ( grade 1; % of doses): Alkaline phosphatase 7%; ALAT: 13%; Bilirubin 0. A similar pattern was seen in the 10 relapsed patients consolidated with Mylotarg as monotherapy. One patient receiving an allogeneic transplant 3 months after Mylotarg treatment developed fatal VOD. Three other patients who undervent allogeneic stem cell transplantation 2, 2 and 3 months, respectively, after the administration of Mylotarg did not experience severe hepatic complications.
We compared twelve courses of Mylotarg combined with DaunoXome and high dose cytarabine with ( n=10) or without ( n=2) added fludarabine and etoposide, administered to10 patients in 1st relapse with 8 similar courses but without Mylotarg, administered to 7 patients with similar characteristics regarding age, CR1 duration and cytogenetics ( mean Mylotarg dose 4.4 mg/m2). More cases of grade 3 diarrhea ( 33% vs 13%) and bacteremia ( 67% vs 38%) were seen in the Mylotarg group, in which three patients suffered hypoplastic deaths. One of these patients developed intestinal perforation following postremission treatment. The two other patients, with an early refractory relapse, and a late relapse with high risk chromosomal aberation, respectively, died from infectious complications following 20 and 36 days of profound neutropenia. These 3 patients recieved 5.9, 8.3 and 5.0 mg/m2 respectively, compared to the average Mylotarg dose of 4.4 mg/m2.
Conclusion: Mylotarg seems to increase toxicity when added to intensive chemotherapy in relapsed AML. The feasibility of this approach must await further studies evaluating toxicity, appropriate dosing and response pattern. When administered as consolidating monotherapy toxicity is modest.
Evaluation of Humoral Response to Trivalent Influenza Vaccination in Patients with Non-Hodgkin Lymphoma Previously Treated or Untreated with Chemotherapy.
Authors: Centkowski Piotr , Brydak Lidia , Machala Magdalena , Kalinka Ewa , Blasinska-Morawiec Maria , Wegrzyn Joanna , Skotnicki Aleksander , Federowicz Irena , Walewski Jan , Seferynska Ilona , Bilinski Przemyslaw , Warzocha Krzysztof ,   for the Polish Lymphoma Research Group
Published: October 2019

Abstract
The aim of this study was to assess humoral response to influenza vaccination in 47 patients with non-Hodgkin lymphoma (NHL) in comparison with 45 healthy individuals (age 12–76 years, median 41 years; 13 males and 32 females). Patients (age 36–82, median 60 years; 24 males and 23 females) consisted of two groups, previously treated with chemotherapy (group A, n=32) or untreated (group B, n=15). In autumn 2003, all subjects were vaccinated with influenza vaccine ([Isquo]influvac’, Solvay Pharmaceuticals B.V.). Antibody responses to influenza hemagglutinin and neuraminidase were determined in sera collected before and 1 month after vaccination by hemagglutination and neuraminidase inhibition tests. Statistical analysis was performed using the Mann-Whitney unpaired and Wilcoxon paired tests. After vaccination geometric mean antibody titers (GMTs) of antihemagglutinin (HI) antibodies significantly increased (p<0.05) and mean fold increases (MFIs) from 10.3 to 26.7 in group A, 5.9 to 48.9 in group B and from 9.1 to 24.4 in the controls. Pre-vaccination protection rate, i.e. the number of subjects with the protective HI antibody titers >1:40, ranged from 0% to 9.4% in group A, 0% to 13.3% in group B and from 2.2% to 20% in the controls. After vaccination protection rates increased and ranged from 78.1% to 87.5%, 73.3% to 93.3% and 66.7% to 82.2%, respectively. Response rates, i.e. the number of subjects with at least 4-fold increase of HI antibody titers after vaccination, ranged from 59.4% to 84.4%, 73.3% to 86.7% and from 51.1% to 66.7%, respectively. In both study groups and in the controls, post-vaccination antineuraminidase (NI) antibody titers were higher (p<0.05) than pre-vaccination titers. MFIs of NI antibody levels ranged from 9.8 to 17.3 in group A, 6.5 to 10.9 in group B and 4.8 to 10.3 in the controls. After vaccination, only hemagglutinin H1 antibody titers were (p<0.05) higher in the controls than in the study group A and B. In the other cases, there were no statistically significant differences between groups or there were higher values in patients with NHL than in the control group. The results of this study indicate that influenza vaccine is immunogenic in patients with NHL and stimulates production of HI and NI antibodies in the titers comparable to healthy subjects.
Clinical Significance of Bcl-2 and Ki67 Protein Expression in Agrressive Non-Hodgkin Lymphoma.
Authors: Stavric Sonja S. Genadieva , Zografski Gore G. , Ivkovski Ljube L.J. , Siljanoski Nikola N. , Georgievski Borce B. , Stojanoski Zlate Z. , Pivkova Aleksandra A. , Cevreska Lidija L. 
Published: October 2019

Abstract
Aggressive Non-Hodgkin lymphoma (NHL) is heterogeneous group with respect to clinical, histopatological and evaluative features. The International Prognostic Index (IPI) has provided a widely accepted prognostic set of criteria to design therapy. However, IPI dose not determine whether routine phenotypic features, beside IPI, may influence survival. We evaluate the prognostic significance of Bcl-2 and Ki67 protein expression in relation to clinical presentation and outcome.
In the period 1989–2002,two hundred eleven patients with newly diagnosed aggressive NHL were recorded in our Department. In this study we included patients with available biopsy sample. Protein expression was analyzed on paraffin embedded tumor tissue by imunohistochemistry in relation to clinical factor and outcome. The expression of more than 20% of neoplastic cell was considered positive for bcl-2, and more than 60% for Ki-67. Comparison was made by x2 test. Survival curves were considered by Kaplan-Meyer method and compared by the long-rank test. Sixty seven patients were recorded and their characteristic were: median age 53 years, stage III and IV, 67%; present B symptoms 44%,; bone marrow infiltration 29%, elevated LDH 58%, performas status more then 1– 26%; extra nodal sites more than 2 –34%. All 62 patients received antracyclin based combination chemotherapy, 72% CHOP regiment.
Overall survival was 52% with a follow up 6–183 months. Bcl-2 expression was observed in 35,5% (22pts) and Ki67 positivity over 60% in 20 pts (30%). Overall survival was influenced by bcl-2 and Kli67 expression. Bcl-2 positive cases were significantly associated with lower overall survival (20% vs. 58%; p<0.01). Overall survuval was significantly worse in patients with Ki67 positivity over 60% (27% vs. 49%; p<0.05)
Bcl-2 and Ki67 monoclonal antibody immunostaging appears to be a simple and reproducible method of determining biological potential of tumor cells and provides useful prognostic information in patients with aggressive NHL.
Cladribine (2-CdA) Effectiveness in Patients with Low Grade Non-Hodgkin’s Lymphoma - 7 year Polish Study Report.
Authors: Ceglarek Bernadeta B. 
Published: October 2019

Abstract
2-Chlorodeoxyadenosine (2-CdA, Cladribine) was used in patients with advanced, low-grade lymphomas (Lymphoplasmacytoid, Centroblastic/centrocytic, Centrocytic, Lymphocytic) resistant to conventional therapy. There was conducted a trial of 2-CdA group versus control group (patients treated different chemotherapy: Chlorambucil, COP, CHOP) in 85 patients. There were 47 men and 38 women with median age of 55 years were treated. Forty five patients with low-grade lymphomas were given 2-CdA at 0.1 mg/kg/d as a 7–5 day continuous infusion every 4–6 weeks. A total number of courses was different (2–7), median of three courses per patient, of 2-CdA were administered. All patients were evaluable for toxicity and for response.
The results of overall response for 2-CdA group and control group are in table 1.
Table 1- The results of overall response for 2-CdA group and control group
2-CdA Group Control Group P CR (%) 16.7 10.8 p>0.5 PR (%) 28.3 43.2 p>0.5 Overall (%) 45.0 54.0 p>0.5
The results of 2-CdA therapy are showed in tabel 2.
Table 2 - The results of 2-CdA therapy in low grade NHL patients.
2-CdA First line therapy II–III line therapy P Numbers of pts. 15.0 30.0 CR (%) 15.2 15.4 p>0.05 PR (%) 30.3 30.8 p>0.05 Overall (%) 45.5 46.2 p>0.05
The results of 2-CdA therapy LG NHL patients (I-6pts; II-7pts.; III-25pts.; IV-7 pts.) concerned with clinical stage are showed below:
Clinical Stage-CR (%)
I-50
II-42.9
III-12
IV-14.3
P>0.05
Clinical Stage-PR (%)
I-33.3
II-42.9
III-40.0
IV-28.6
P>0.05
Toxicity, in particular opportunistic infections (< or = grade 2, 35.6–48.4% in 2-CdA group v 31.6–64.7% in chemotherapy treated group; P>0.05) and myelosuppression (< or = grade 2 leucopenia, 31.1% in 2-CdA group v 25.0% in chemotherapy treated group, P>0.05 and thrombocytopenia 0–II grade WHO), were more frequent in 2-CdA group (II–III line therapy). The median response duration was 12 months (range, 3 to 44+). I observed less death numbers in 2-CdA first line patients than II–III line 2-CdA group (P=.00132).
Conclusions : There was no statistical significant difference in frequency overall response (CR+PR) between 2-CdA group and chemotherapy treated group.
2-CdA therapy as a consecutive line caused an increase in mortality risk in contrast to the first line therapy.
2-CdA therapy as II–III line therapy allowed to receive complete remission in 9.4% previously treated low grade non Hodkin’s lymphoma patients.