bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autoimmune Disease Is a Risk Factor for the Development of Non-Hodgkin’s Lymphoma and May Account in Part for Its Increase in Women.
Authors: Cuttner Janet , Spiera Harry , Troy Kevin , Wallenstein Sylvan 
Published: October 2019

Abstract
The incidence of non-Hodgkin’s lymphoma (NHL) has increased dramatically over the last several decades especially in people over 60 years of age. The reasons for this are likely to be multifactorial and may include a diminution of immune surveillance which occurs with aging. Patients with autoimmune disease may be at increased risk of developing NHL. Women have a higher incidence of autoimmune disease (AIMD). The use of immunosuppressive drugs to control autoimmune diseases decreases immune surveillance and may therefore increase the likelihood of developing lymphoma. We sought to determine if prior autoimmune disease increases the risk of developing NHL.
Methods: All patients seen by JC & KT from 1993 to 2002 form the basis of this report. There were 278 patients with NHL and these were compared with 317 patients with other hematological disorders (controls) seen at the same time period.
Findings: Thirty-six (13%) of NHL patients had an autoimmune disease prior to or at diagnosis of NHL compared to 5% of controls (p=.001). Sixty-nine percent of NHL patients with a prior AIMD were female compared to 43% without a prior AIMD and this was similar in control patients (69% and 48%) respectively. Twenty percent of all women with NHL had a prior history of autoimmune disease compared to 7% of women in the control group (p=.001). A logistic regression was performed to evaluate simultaneously the effects of gender, age and AIMD on disease status. Even adjusting for age and gender, autoimmune disease was significantly more likely to be associated with NHL, with an odds ratio of 2.6 and 95% confidence intervals of 1.4–4.9. Thus for patients of the same age and gender, patients with AIMD are 2.6 times more likely to have NHL than the control patients. The median time from AIMD to the diagnosis of NHL was 10 years. It was 14 years in the control group. The two most common autoimmune diseases in the NHL patients were rheumatoid arthritis and autoimmune hypothyroidism. In the control group it was autoimmune hypothyroidism and inflammatory bowel disease.
Conclusion:
Autoimmune disease may account in part for the increase in NHL especially in women.
Evaluation of Early Stage Hodgkin’s Lymphoma Treatment: Two Decades of Progress.
Authors: Alsaeed Eyad F. , Samant Rajiv , Victor Gallant , Huebsch Lother , Kendal Wayne 
Published: October 2019

Abstract
Introduction
The treatment of early stage Hodgkin’s lymphoma is controversial. Radiotherapy alone, chemotherapy alone or a combination of radiotherapy and chemotherapy are all considered effective options.
Purpose
The purpose of this study is to review the treatment approaches and outcomes used for early stage Hodgkin’s lymphoma over the past two decades at ORCC
Methods
Retrospective chart review of all patients with stage IA /IIA treated from 1984–2002 was performed. Patients were separated into three groups according to initial treatment modality: radiation alone (Rads), chemotherapy alone (Chemo), or combined modality (Combined). Disease-free survival and overall survival were estimated using the Kaplan-Meier analysis.
Result
Between May 1984 and January 2003, 172 patients with newly diagnosed Hodgkin’s lymphoma (28% stage 1A, 72% stage 2A) were seen at our centre. Treatment was as follows: 49% Rads, 13% Chemo and 38% Combined. The median age was 33.7 years (range: 17 – 82 years) and the median follow-up of 73 months (range: 3 – 204 months). The 5-year disease free and overall survival rates for the entire group were 90% and 96 % respectively. The 5-year disease-free and overall survival by treatment modality was: Rads 87% and 93 %; Chemo 80 % and 100 %; Combined 97 % and 98%. In the Combined group, there was no difference in outcome between patients receiving involved-field radiation and those receiving extended-field radiotherapy. The relapse rate in a patient who received abbreviated chemotherapy and greater than four cycles was 4.3% (1 out of 23) and 2.4% (1 out of 41) respectively. The incidence of acute Grade 3 and 4 toxicities were 9 % and 0.5% respectively.
Conclusions
Our data confirms the excellent prognosis of early stage Hodgkin’s lymphoma with all the approaches used at our centre. At present, we favour combined modality treatment with involved-field radiotherapy and our results support its continued use.
Study on Specific Anti-Leukemia Function of Dendritic Cells (DC) Vaccine Induced from Chronic Myeloid Leukemia (CML).
Authors: Qiao ZhenHua , Zheng Z.Z. , Zhu L. 
Published: October 2019

Abstract
Objective In this article, we explore the feasibility of dendritic cells (DCs) induced from chronic myeloid leukemia (CML) with different cytokine cocktails and the mechanisms of immunological responses by specific T lymphocytes primed by this kind of DC vaccine.
Methods Monocytes (MNCs) for the generation of DC were collected from patients with high numbers of circulating peripheral blood CML cells, then cultured with different cytokine cocktails in different cultural medium (Fetal calf serum or Human serum albumin medium) to induce DCs. DCs were studied for morphology and immunofluorescent staining. RT-PCR was used to analyze the specific fusion genes and chromosome banding technique were used to detect Philadelphia chromosome (ph’). In vitro, DCs were used to induce auto-lymphocytes to be activated CTL, killing rates and T subgroups were assayed, IL-12 contents in the supernents were assayed also.
Results After induction, all these CML-derived MNCs developed typical DC morphology and the DC-associated surface molecules upregulated. The contents of IL-12 in the co-culture system of CML-DC and lymphocytes increased and the activated lymphocyte skewed from Th1 to Th2. At and effector: target ratio of 20:1, 80.67±6.43%, 62.33±12.01%, 23.92±5.62% cytotoxicity was noted with CML-DC/AL against autologous leukemia cells, K562, HL60, exhibiting more killing activities to auto-CML cells than K562 and HL60 cell.
Conclusion The results of this research will supply new approach for specific immunotherapy of CML and supply the application value for the CML derived DC vaccine against CML.
Imatinib Does Not Inhibit Neutrophil Oxidative Burst Function in Patients with Chronic Myelogenous Leukemia (CML).
Authors: Eksioglu-Demiralp Emel , Bizargity Peyman , Adiguzel Cafer , Ozilhan Gozen , Bayik Mahmut 
Published: October 2019

Abstract
Imatinib mesylate is a competitive Bcr-Abl tyrosine kinase inhibitor which has been used in treatment of chronic myelogenous leukemia (CML). In addition to the inhibition of the Bcr-Abl protein tyrosine kinases, it also shows activity against other protein kinases such as platelet-derived growth factor receptor (PDGF-R), c-Kit and protein kinase C (PKC) in higher doses (Manley et al., 2002). Myelosuppression has been reported up to 60% of patients with CML under imatinib therapy (Deininger et al., 2003). Microbicidial activity of the neutrophils is mainly generated by the enzyme NADPH oxidase which produces superoxide anion. Several protein kinases including protein kinase C (PKC) that phosphorylate components of the NADPH oxidase and regulate oxidase activity have been identified. Little has been known about the effect of imatinib on neutrophil function, so far. Therefore, we aimed to evaluate the neutrophil respiratory burst activity using Phorbol Myristate acetate (PMA), a PKC activator, in vitro, in patients with CML achieving imatinib. Heparinized peripheral blood samples were collected from 14 patients with CML under imatinib therapy (400 mg daily) for 9.4 ± 4 months and 13 voluntary healthy controls. Oxidative burst was evaluated using a standard method defined previously by flow cytometry (Robinson et al., 1993) Oxidative burst stimulation index was calculated as the ratio of mean value of fluorescence intensity of DCFH-DA labelled neutrophils before and following PMA stimulation. It has been found that the stimulation index of neutrophils in patient achieving imatinib was 14.5±5 which was comparable to healthy control group 14±6.6. Furthermore, no serious infection disease was clinically detected during 8 month follow up period. So this study suggest Imatinib which has ability to inhibit bcr-abl fusion protein selectively and also can inhibit some others kinases, however has no inhibitory effect on the neutrophil function in patients with CML.
Effect of 5-Aza-2′-Deoxycytidine in High-Risk Myelodysplasia Cells in Vitro.
Authors: Tong Hongyan , Lin Maofang , Jin Jie 
Published: October 2019

Abstract
5-Aza-2′-deoxycytidine (5-Aza-CdR; Decitabine) is an active antineoplastic agent in patients with leukemia. Due to its unique mechanism of action of demethylating DNA, 5-Aza-CdR has the potential to activate tumor suppressor and differentiation genes that have been accidentally silenced by DNA methylation in leukemic cells. Since5-Aza-CdR can induce clinical remissions in patients with high-risk myelodysplastic syndromes (MDS), we therefore attempt to investigate the mechanisms of the effect of 5-Aza-CdR by using MUTZ-1 cells in vitro, which are confirmed as a high-risk myelodysplasia Cell line that derived from a MDS patient (FAB subtype refractory anemia with excess of blasts). Our results indicated that 5-Aza-CdR showed inhibition of the growth of MUTZ-1 cells. The IC50 values of 24 hours, 48 hours and 72 hours were 6.75mmol/L, 2.82mmol/L and 5.45mol/L respectively. Characteristic changes of apoptosis emerged in MUTZ-1 cells after being exposed to 5-Aza-CdR in the different concentration from 0.8 mmol/L to 3.2 mmol/L, and the positive cells of Annexin VFITC on the membrane of MUTZ-1 cells were analyzed by flow cytometry. The percentage of apoptosis cells treated by 5-Aza-CdR at a dose of 3.2mmol/L for 48 hours was higher than that in untreated cells (16.7%±5.3% vs 2.9%±1.2%, p<0.05). The CpG islands in the promoter regions of p15INK4B gene were found to be hypermethylated in MUTZ-1 cells, resulting in a significant reduced expression of p15INK4B gene in the cells. However, the expression of p15INK4B gene was recovered and the methylation level of p15INK4B gene was also decreased (densitometry readings: 253.994±26.536 vs 369.641±28.915, p=0.003), after the cells exposed to 5-Aza-CdR at a dose of 3.2 mmol/L for 48 hours. Furthermore, 5-Aza-CdR could significantly down-regulate the expressions of DNA methyltransferase genes DNMT3A, which encodes a deno methyltransferase, at mRNA level in a dose dependent manner(r=−0.879,p=0.03). However, it had no effects on DNMT3B gene and DNMT1 gene that codes a maintenance methylase. The expression level of DNMT3A mRNA in MUTZ-1 cells treated with 5-Aza-CdR at a concentration 3.2 mmol/L for 48 hours was lower than that in untreated cells (densitometry readings:0. 385±0.086 vs 0.654±0.074 p<0.05). These observations suggest that 5-Aza-CdR can inhibit the growth and induce the apoptosis of MUTZ-1 cells within the range of concentration from 0.8 mmol/L to 3.2 mmol/L, which might be one of the mechanisms of antitumor effects of 5-Aza-CdR. The drug can activate the expression of p15INK4B gene in MUTZ-1 cells by demethylation of the p15INK4B gene through inhibiting the expression of DNMT3A gene. That might be the mechanisms of 5-Aza-CdR in the treatments of MDS.
Increased Platelet Turnover and Platelet P-Selectin in Patients with Essential Thrombocythemia and Thrombosis.
Authors: Arellano-Rodrigo Eduardo , Alvarez-Larran Alberto , Cervantes Francisco , Reverter Juan-Carlos , Villamor Neus , Montserrat Emili 
Published: October 2019

Abstract
Essential thrombocythemia (ET) is a myeloproliferative disorder associated with an increased tendency to thrombosis, the pathogenesis of which is not well known. The aim of the present study was to analyze the relationship between platelet turnover and activation and a history of thrombosis in patients with ET. The expression of platelet P-selectin (measured both in unstimulated platelets and after agonist-stimulation with ADP, thrombin, arachidonic acid (AA), collagen or epinephrine) and the percentage of reticulated platelets (RP) were measured in 53 ET patients with (n=26) or without (n=27) previous thrombosis and in 26 healthy controls. Both variable were assessed using quantitative whole blood cytometry and the results were expressed as percentages and in MESF (molecules of equivalent soluble fluorochrome) units. The results were as follows: 1) patients with thrombosis showed a significantly higher basal platelet P-selectin expression (6.1%, 95% CI: 4.6–6.8) than those without thrombosis (4.6%, 95% CI: 3.7–5.5)) and the healthy controls (3%, 95% CI: 2–4.2) (p= 0.0001 for all comparisons); 2) following thrombin activation, ET patients had a higher mean percentage of platelet P-selectin expression than the controls (61% versus 46%, p = 0.01), but no difference was seen between the two groups of patients; 3) after AA activation, patients with ET and thrombosis also showed higher platelet P-selectin values (78%, 95% CI: 69–86) than those without thrombosis (63%, 95% CI: 55–76) and the controls (46%, 95% CI: 33–58) (p=0.001 for all comparisons); 4) ET patients with thrombosis had a significantly higher mean percentage of RP (18%, 95% CI: 13–20) than patients without thrombosis (13%, 95% CI: 11–18) and the controls (8%, 95% CI: 5–10) (p = 0.0001 for all comparisons). No differences were observed when the patients were separated on the basis of the treatment that they received at the time of study. The above results point at a possible role of AA-induced platelet acitvation in the development of thrombosis in ET and give conceptual support to the prohylactic use of aspirin in such patients.
Comparison of Cytokine Efficacy on Ex Vivo Expansion of Megakaryocyte (MK) Progenitor Cells between Essential Thrombocythemia (ET) and Normal Person.
Authors: Do Young-Rok , Kwon Ki Young , Song Hong Suk , Kim Heung Sik , Hyun Myung Soo 
Published: October 2019

Abstract
Essential thrombocythemia (ET) is a chronic myeloproliferative disorder (MPD) of insidious onset and characterized by regulatory defect in stem cells. It is possible that ET can induce autonomous megakaryocyte (MK) growth. The physiology of megakaryocytopoiesis was not well defined, and, as a consequence, the pathophysiology of ET characterized by excessive platelet production was poorly understood. Secondary thrombocytopenia, especially post-transplantation, could be fatal so there were many trials to overcome this problem. This experiment was designed to test the effect of cytokines on ex vivo expansion of MK progenitor cells from ET. The MK colony forming unit (CFU-MK) expansion degree according to single or combination cytokines were analyzed in normal person and ET patients. Mononuclear cells were isolated from bone marrow aspiration and then cultured in serum-free medium (MegaCult™) supplemented with SCF, G-CSF, TPO, IL-11 and 3 types of cytokine combination. After 14 days of ex vivo expansion and then the CFU-MK were counted by microscope. In the absence of cytokines, CFU-MK of ET significantly expanded than normal (p<0.05), which represented autonomous CFU-MK formation. There were significantly increased mixed CFU-MK of ET in SCF, G-CSF and TPO (SGT) combined cytokine added well (p<0.05) but pure and total CFU-MK of SGT added well did not show significant expansion. When the effect of cytokines were compared between normal and ET, all of the cytokines significantly expand CFU-MK in ET (p<0.05) than normal and especially in pure CFU-MK. In summary, autonomous MK growth was shown in ET and SGT can be relatively effective cytokine combinations in ex vivo CFU-MK expansion. Further investigation will be needed to find out the most effective culture system and cytokine combination for ex vivo MK progenitor expansion.
Comparison of Antigen-Loading Strategies for DC-Based Immunotherapy of B-CLL.
Authors: Mellstedt Hakan , Kokhaei Parviz , Osterborg Anders , Choudhury Aniruddha 
Published: October 2019

Abstract
The slow indolent nature of B-CLL makes it eminently suitable for immune-based treatment strategies. Currently, there exist very few CLL-associated, defined antigen which can be used in vaccination approaches. The use of whole tumor preparations in conjunction with dendritic cells (DC) as cellular adjuvants presents an alternative method for generating therapeutic T-cell responses in CLL patients. We have examined various strategies of loading DC with whole tumor antigens; viz. tumor-DC hybrids, endocytosed apoptotic bodies, RNA or lysate from B-CLL cells. Dendritic cells were generated in vitro, using GM-CSF and IL-4 from immunomagnetically purified, CD14+ monocyte precursors obtained from the peripheral blood of B-CLL patients. The immature DC were loaded with whole tumor antigen using the above methods and matured using TNFα. The tumor antigen-loaded DC were compared for their ability to stimulate autologous T-cell responses. Among all the antigen-loading methods tested, DC that had endocytosed apoptotic bodies (Apo-DC) consistently generated the greatest numbers and magnitude of reactive T-cells as quantified in proliferation and ELISPOT assays. RT-PCR analysis for cytokine mRNA revealed that T-cells stimulated by Apo-DC resulted in an immune response that was almost entirely of the TH1 type as manifested by the production of mRNA for IFN-γ and TNFα. In contrast, other methods of loading antigen resulted in a mixed TH1-TH2 population with varying amounts of TH2 cytokines like IL-4 and IL-10.
In a separate series of experiments we compared the T-cell stimulatory capacities of cryopreserved and thawed, with fresh antigen-loaded DC. The results of these studies are essential for the development of a protocol for clinical therapy of B-CLL patients using Apo-DC. Our results indicated that cryopreserved DC could be recovered with high viability. A comparison of functional abilities demonstrated that no significant differences in T-cell stimulatory capacity between cryopreserved and fresh Apo-DC could be noted over a wide variety of immunological assays. Cumulatively, our results suggest that Apo-DC may be a suitable vaccine candidate for immunotherapy of B-CLL patients.
A Randomised Controlled Trail of Plasma Exchange in Rapidly Progressive Renal Failure of Myeloma.
Authors: Clark William F. , Stewart A. Keith , Rock Gail A. , Sternbach Marion , Sutton David M. , Barrett Brendan J. , Heidenheim Paul A. , Churchill David N. ,   members of the Canadian Apheresis Group
Published: October 2019

Abstract
In myeloma, plasma exchange (PE) has been suggested to prevent rapidly progressive kidney failure by reducing exposure to nephrotoxic light chains. We carried out a randomized controlled multi-centre trial comparing PE or no PE in 104 patients of whom 101 met the inclusion, exclusion criteria and 4 were lost to follow-up. We compared baseline characteristics as well as renal outcomes and performed a futility analysis to determine the sample size necessary for potential statistical significance for the changes noted. Thirty-nine patients were randomized to the control group and 58 to the PE group with a 6-month follow-up. The baseline characteristics of these 2 groups were similar including serum creatinine, dialysis dependence, age, gender, serum calcium, serum albumin, 24 -hour urine for protein levels and Durie-Salmon myeloma staging. Thirteen (33.3%) of the control group and 19 (33.3%) of the PE group died within 6 months of follow up. Ten patients (31%) in the control and 10 patients (21%) in the PE arm were dialysis dependent at 6 months. Seven patients (47%) came off dialysis in the control and 13 patients (59%) in the PE arm with the mean number of dialysis days from 0–6 months being 45.7±67.6 in the control versus 29.2±56.1 in the PE arm at 6 months. The mean serum creatinine in the control group was 314.6±256.1 μmol/L versus 215.4±215.3 μmol/L in the PE group and the composite end point of death, dialysis or serum creatinine >254 μmol/L occurred in 12 (30.8%) in the control and 11 (19.3%) in the PE arm. The futility analysis to indicate the per group sample size necessary to achieve statistical significance at 6 months for the difference we observed was infinite for cumulative mortality, 805 for dialysis dependence, 2418 for coming off dialysis, 321 for number of dialysis days, 132 for creatinine difference of 100 μmol/L and for the composite outcome of death, dialysis or creatinine>354 μmol/L, 737. We did not observe a statistically significant difference in mortality or renal morbidity for PE versus no PE in patients with myeloma and rapidly progressive kidney failure.
Fetal-Maternal Microchimerism: Basis for a Potential New Therapy for Malignancy?.
Authors: Gilmore Gary L. , Holm Melissa M. , Lister John , Shadduck Richard K. 
Published: October 2019

Abstract
Fetal-maternal microchimerism [MC] occurs during gestation or delivery, as cells traffic from the fetal circulation to the maternal circulation (and vice versa) via the placenta, and persist for decades post-partum. The reported incidence of MC is 33% in normal parous women. To explore the incidence and extent of MC among normal females and cancer patients for potential therapy, we obtained blood samples from 162 normal parous women, and 21 parous cancer patients. 30 non-parous women served as controls. The presence of male DNA was detected using two rounds of PCR with nested sets of primers specific for the Y chromosome. The sensitivity of the assay was validated at 1 male cell per 1 million female cells using DNA prepared from serial dilutions of (male) KG-1 cells in (female) K562 cells. The observed frequency of MC was dependent on the amount of DNA assayed: with 1 ug DNA [~300,000 genomes] per test, the frequency of MC was 18%. At 5 ug DNA [1.5 million genomes], this rose to 46%, and at ≥ 25 ug DNA [7.5 million genomes], 66% of normal parous women had MC. Among parous cancer patients, MC was present at 20% with 5 ug DNA, rose to 76% when ≥ 25 ug DNA or more was tested. The lower frequency of MC among cancer patients at 5 ug DNA may reflect the effects of prior chemotherapy. 2 out the 30 normal non-parous donors were chimeric; this number did not increase when more DNA was assayed. The reason for the MC among non-parous subjects is unclear. Our results indicate the MC is much more frequent among parous women than previously reported. Provided that MC confers long-lasting tolerance of fetal tissue antigens, this suggests that son-to-mother cellular therapy may be feasible for treatment of malignancy.