bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utility of FDG-PET and Comparison of FDG-PET and Ga-67 Scintigraphy in Evaluation of B-Cell Indolent Lymphoma.
Authors: Tsukamoto Norifumi , Yokohama Akihiko , Irisawa Hiroyuki , Saitoh Takayuki , Uchiumi Hideki , Matsushima Takafumi , Nojima Yoshihisa , Karasawa Masamitsu , Handa Hiroshi , Murakami Hirokazu 
Published: April 2020

Abstract
18Fluoro-2-deoxyglucose positron emission tomography (FDG-PET) has emerged as an important tool for the management of lymphoma patients, but little information has been reported about its usefulness in indolent lymphoma. The aim of this study was to retrospectively assess the usefulness of FDG-PET, and to compare the sensitivity of FDG-PET with gallium 67 citrated scintigraphy (Ga-67), in identifying disease involvement in patients with indolent lymphoma. We also investigated the relationship between FDG-PET and pathologic diagnosis according to the World Health Organization (WHO) classification system.
A total of 118 cases contemporaneously underwent FDG-PET and CT and/or MRI prior to treatment. The histological diagnoses included follicular lymphoma (FL; n=43), MALT-lymphoma (n=52), splenic marginal zone lymphoma (SMZL; n=10), small lymphocytic lymphoma (SLL; n=5) and mantle cell lymphoma (MCL; n=8). In 88 of these 118 cases, Ga-67 was also performed. The involved disease sites were divided into lymph node regions and extranodal regions. The former group was further divided into four lymph node regions:
head and neck, chest, abdomen and pelvis.
Among the 118 patients, 401 disease sites were included in the analysis. FDG-PET identified disease sites in 171/189 (90%) FLs, 107/126 (86%) MALTs, 7/16 (44%) SMZLs, 10/19 (53%) SLLs and 51/51 (100%) MCLs. In addition, FDG-PET detected more involvement sites than Ga-67 for all disease sites, except for one region each in the MALTs and SMZLs, namely the eyelid and spleen. Ga-67 was able to detect disease sites assessed by FDG-PET in 48/127 (38%) FLs, 44/78 (56%) MALTs, 3/5 (60%) SMZLs, 1/2 (50%) SLLs and 8/27 (30%) MCLs. There were no anatomical differences in the not-detected disease sites between FDG-PET and Ga-67.
In imaging lymphomas before therapy, FDG-PET was informative for FL, MALT, and MCL, but less reliable for SMZL and SLL. Ga-67 was not suitable for indolent lymphoma, in particular FL and MCL. Given the high sensitivity of FDG-PET, this modality is highly recommended for indolent lymphoma. However, for SMZL and SLL, different anatomical imaging modalities such as CT and MRI should be used.
Sensitivity of FDG-PET Histology No.of sites FDG-PET positive % FL 189 171 90 MZL/MALT 126 107 86 MCL 51 51 100 SMZL 16 7 44 SLL 19 10 53 Total 401 346 Comparison of FDG-PET with Ga-67 Histology PET positive Ga-67 positive Ga/PET(%) FL 127 48 39 MZL/MALT 78 44 56 MCL 27 8 30 SMZL 5 3 60 SLL 2 1 50 Total 239 104
Racial Disparities in Diffuse Large B Cell Lymphoma: A VA Population Study.
Authors: Maraboyina Sanjay , Komrokji Rami S. , Haddad Rami Y. , Nahleh Zeina A. , Safa Malek M. 
Published: April 2020

Abstract
Background: Racial disparities in diffuse large B cell non-Hodgkin’s lymphoma (DLBCL) are not well studied. Racial differences in outcome are not well recognized given majority of patients with DLBCL are white. The VA health care system offers a platform to study those racial differences given similar other variables and socioeconomic status among those patients.
Methods: This was a retrospective analysis. The VA Central Cancer Registry (VACCR) database was used to identify patients with DLBCL diagnosed between 1995 and 2005. There are approximately 120 VA medical centers diagnosing and/or treating patients with cancer. The VACCR aggregates the data collected by the medical centers’ cancer registries. Data were extrapolated and analyzed using bio-statistical software SPSS. Variables included age, sex, stage of disease, histology subtype, date of diagnosis, date of last contact, date of relapse, vital status, family history of cancer, tobacco history, alcohol history, Agent orange exposure and whether patients received chemotherapy and or radiation. Independent t test was used for comparing continuous variables and chi square test for categorical variables. Wilcoxon test was used to compare survival among the two groups.
Results: There were 2792 patients with DLBCL at the VA system, 2402 white and 323 black patients. Sixty-seven patients from other racial groups were excluded from this analysis. The mean age of presentation among blacks was 57.8 years compared to 65.7 years among whites (P-value &lt; 0.005). More Black patients had history of alcohol use, and smoking. More white patients had family history of cancer. No differences in histology subtypes were observed. Other baseline characteristics were similar. No difference in stage of disease was noted at presentation. IPI score data were not available. Similar proportion of patients received multi-agent chemotherapy among the two groups, 70 % for blacks and 67% for whites (P-value 0.58). Among blacks 16 % of patients received radiation while 19.5 % white patients did (P-value 0.73). The 5-year overall survival for blacks was 24 % compared to 29% for whites (P-value 0.92, Wilcoxon test). No statistically significant differences in survival were noted between the two races within each clinical stage. Using Cox regression multivariable analysis age, stage and chemotherapy were the only statistically significant independent variables affecting survival.
Conclusions: DLBCL is less common among blacks. Blacks diagnosed with DLBCL are more likely to present at younger age. The treatment and outcome of DLBCL among blacks are not different from whites within the VA system.
Proteosome Inhibitor Treatment Down-Regulates S-Phase Kinase-Associated Protein 2 Causing Inhibition of Proliferation and Induces Apoptosis in Primary Effusion Lymphoma.
Authors: Hussain Azhar R. , Al-Jomah Naif A. , Sultana Mehar , Pulicat Manugaran S. , Al-Kuraya Khawla S. , Uddin Shahab 
Published: April 2020

Abstract
Proteosome inhibition is a novel approach for treating malignancy and has been approved for clinical use. The proteosome is the primary proteolytic mechanism in eukaryotic cells and inhibition of its catalytic activity initiates a cascade of events affecting cell cycle and apoptotic activities. These activities ultimately lead to cell cycle arrest and apoptosis in malignant cells however, the normal counterpart of these cells are spared. In this study, we used a panel of primary effusion lymphoma cell lines (BC1, BC3, BCBL1 and HBL6) to study the effects of proteosome inhibitor, MG132 on cell proliferation and apoptosis. Our data showed that proteosome inhibitor MG132 decreased cell viability as well as induced apoptosis in a dose dependent manner ranging from 0.5–10μM. Furthermore, treatment with 2.5μM MG132 for 24hours induced 41% apoptosis in BC1, 51% in BC3, 41% in BCBL1 and 48% in HBL6 cell lines as detected by annexinV/PI dual staining. S-phase kinase-associated protein 2 (skp-2) is a proto-oncogene and over expressed in various types of tumors. We sought to determine the role of Skp-2 following proteosome inhibition in PELs. MG132 treatment of PEL cell lines resulted in down-regulation of SKP-2 protein in a dose dependent manner whereas the expression of p-27 was up-regulated demonstrating an inverse relationship between these two proteins. Furthermore, MG132 treatment of PELs led to conformational changes in Bax protein and translocation to the mitochondria leading to the loss of mitochondrial membrane potential with subsequent release of cytochrome c from mitochondria into cytosol. Cytochrome c release caused activation of caspase-3 followed by polyadenosin-5′-diphosphate-ribose polymerase (PARP) cleavage. In addition, proteosome inhibitor treatment also caused down-regulation of inhibitor of apoptosis protein, XIAP. Taken together, our findings show that proteosome inhibition causes down-regulation of skp-2, up-regulation of p-27, inhibition of proliferation as well as caspase-dependent apoptosis in primary effusion lymphoma cells suggesting a role of proteosome inhibitors in the treatment of these aggressive cancers.
Detection of Clonality in Lymphoproliferations Using PCR of the Antigen Receptor Genes: Does Size Matter?.
Authors: Rothberg Paul G. , Vargas Roberto L. , Felgar Raymond E. , Polochock Susan L. , Frazier Sharon D. 
Published: April 2020

Abstract
A biopsy of a nasal mass was received from another institution for a hematopathology consultation. The specimen had morphologic and immunostaining features consistent with a B-cell lymphoma, histologically low-grade, and suggestive for an extranodal marginal cell lymphoma of mucosa associated lymphoid tissue (MALT) type. We used PCR of the IgH gene to evaluate clonality on DNA derived from this specimen. The primers were from the BIOMED-2 report (van Dongen et al. 2003, Leukemia17:2257) and the amplicons were subjected to heteroduplex formation prior to PAGE. A homoduplex of approximately 140 bp was obtained reproducibly from the FR2 and JH primers, which is below the usually acceptable size limits of 250–295 bps. No homoduplex was obtained using FR3 and JH primers. We sequenced the FR2/JH amplicon using the PCR primers as sequencing primers. The amplicon was 137 bps, with 92 bps between the primers. After the upstream VH3 FR2 primer there were approximately 25 bps from the FR2 region of several members of the VH3 family, with VH3-49 (allele *03) being the best match. Adjacent to the downstream consensus JH primer there were approximately 30 bp from the J6 segment. Between the identifiable sequences there were 37 bp that we could not identify. Blast searches turned up several matches of 18 bp, but nothing that gave convincing evidence for its origin. We interpret these results as indicating a clonal IgH rearrangement followed by a deletion that removed most of the downstream portion of the V segment, including the FR3 region. It is likely that the 37 bp in between the identified IgH segments consists of randomly inserted nucleotides and IgH sequence that has been somatically mutated beyond recognition, although other interpretations are possible. However, the amplicon does appear to be derived from an IgH rearrangement, which is consistent with derivation from a monoclonal population of B-lymphocytes. This work illustrates that DNA fragments outside of the size range expected from PCR of the antigen receptor genes may still be consistent with a monoclonal result. Thus, this type of result should not be dismissed, but should be subjected to further analysis.
Involvement of the Lyn Interactome in the Regulation of Erythropoiesis.
Authors: Ingley Evan , McCarthy David J. , Samuels Amy L. , Schneider Jessica R. , Payne Christine J. , Klinken Svend Peter 
Published: April 2020

Abstract
Src family kinases, such as Lyn, are involved in signalling pathways regulating a myriad of cellular processes. We have shown previously that Lyn is involved in differentiation signals emanating from activated erythropoietin (Epo) receptors. We have highlighted the importance of Lyn to red cell maturation in vivo with Lyn−/ − mice, which develop anaemia and display extramedullary stress erythropoiesis. Here, we show that ex vivo cultures of primary Lyn−/ − erythroblasts display an imbalance between proliferation and differentiation. In addition we have identified several new Lyn pathways. One centres on Cbp (Csk binding protein), an adaptor protein that recruits negative regulators Csk/Ctk. Our data show that Lyn phosphorylates Cbp, which then recruits Csk/Ctk to suppress Lyn kinase activity. Intriguingly, through the use of a phosphotyrosine-specific yeast two-hybrid assay that we developed, phosphorylated Cbp also binds SOCS1, another well-characterised negative regulator of cell signalling - this results in elevated ubiquitination and degradation of Lyn in Epo-stimulated erythroid cells. Altering Cbp expression in primary erythroblasts significantly affected their ability to transmit Epo-receptor signals and differentiate correctly. Another Lyn pathway we have identified centres on a novel molecule we termed LACM, which transmits Lyn signals to Vav2 and Nckβ via phospho-tyrosine-specific interactions. These novel associations regulate the cytoskeleton/cell shape, which lead to changes in cell attachment and migration. Significantly, primary erythroblasts from Lyn−/ − mice display altered subcellular localization of LACM. Another novel Lyn interactor (LIAR) regulates nuclear import/export of signalling molecules - impairing LIAR’s normal function inhibits primary erythroblast development. Taken together, these results illustrate that Lyn is intimately involved in multiple signalling complexes, which play crucial roles in regulating numerous aspects of red blood cell biology.
Primary Systemic Anaplastic Large Cell Lymphoma in Korean Adults; Retrospective Analysis of 36 Patients.
Authors: Park Soo Jung , Kim Shin , Lee Dae Ho , Jeong Yong Pil , Bae Yunjeong , Huh Jooryung , Han Eun Mee , Suh Cheolwon 
Published: April 2020

Abstract
Anaplastic large cell lymphoma (ALCL) is a CD30+ T-cell non-Hodgikin’s lymphoma and represents only 2–8% of lymphoma overall. Information on clinical finding and response to treatment of primary systemic ALCL is still limited in Korea. The aim of this study was to report our experience thirty-six cases with focusing on the clinical feature, treatment response, survival, and prognosis. We retrospectively reviewed the medical records of the patients who were diagnosed as primary systemic ALCL at the Asan Medical Center from February 1995 through December 2005. The median follow up period was 47 months. The median age was 39 years (range, 17–67). The ratio of male to female was 4.14. Patients with primary systemic ALCL had high frequency of advanced-stage disease and extranodal involvement. Seventy-two percent of patients showed Ann Arbor stage III and IV. The most common involved extranodal sites were bone (19%) and soft tissue (17%). Thirty-two (89%) patients were treated by anthracycline-based regimen (CHOP) as induction chemotherapy. Sixteen patients (44%) obtained CR and 14 patients (39%) attained PR, with overall response rate of 83%. The overall survival and disease-free survival was 49 and 17 months. In ALK-positive patients, median overall survival was not reached in follow up period and 3-year overall survival was 61%. In ALK-negative patients, median overall survival was 53 months and 1-year and 3-year overall survival was 75% and 40% respectively. On univariate analysis, international prognostic index (IPI) was significant prognostic factor for overall survival (p = .03). But ALK expression did not affect overall survival in Korea (p = .78). There was no independent prognostic factor for overall survival in multivariate analysis. This retrospective analysis contributes to our understanding of clinical aspects for patients with primary systemic ALCL in Korea. Overall survival is 49 months and overall response to CHOP chemotherapy is 83%. IPI is important predictor of overall survival, but ALK expression may not provide prognostic information for primary systemic ALCL in Korea.
Immunohistochemical Expression Pattern of Germinal Center and Non-Germinal Center Markers Correlates with Prognosis in Diffuse Large B-Cell Lymphoma.
Authors: Chiattone Carlos , Carvalho Marineide P. , Paes Roberto P. , Ribeiro Karina C.B. , Soares Fernando 
Published: April 2020

Abstract
Recent studies have shown correlations between diffuse large B-cell lymphoma (DLCBL) prognosis and molecular features using genome profiles by cDNA microarrays. Since this analysis is not routinely used, immunohistochemical tests for prediction of DLBCL survival are gaining major importance, using markers as, CD10, BCL-6 and MUM-1 to identify germinal center B-cell (GCB) and non-GCB, respectively. The goal of this study was to evaluate the significant effect on survival within GCB and non-GCB subgroup.
Patients and Methods: Seventy-four untreated pts (median age: 58 yrs: 38M/36F) with DLBCL de novo diagnosed in a single institution, treated with CHOP-like regimens. Tissue microarrays (TMA) blocks were created from paraffin-embedded, formalin-fixed block and stained with antibodies to CD20 (clone L26, Dako), CD10 (clone 56C6; Novocastra; NCL-CD10-270), BCL-6 (clone GI 191E/A8; Cell Mark; CMC 798) and MUM1 (clone MUM1p; Dako, CA; M7259). Results. Cases were subclassified using CD10, BCL-6, and MUM1 expression, and 25 cases (33.8%) were considered GCB and 49 cases (66.2%) non-GCB. The 2-year overall survival (OS) for the GCB group was 80% compared with only 38.9% for the non-GCB (p&lt;0.001). In the multivariate analysis, only the International Prognostic Index score (IPI 3-4 HR=2.6, p=0.013) and the GCB phenotype (Non-GCB HR=2.7, p=0.054) were independent prognostic factors. In summary, immunohistochemical expression of CD10, BCL-6 and MUM1 are able to determine the GCB and non-GCB subtypes of DLBCL and predict survival.
CCR5 Chemokine Receptor Expression Can Promote Disease Progression in Non-Hodgkin’s Lymphoma.
Authors: Mazur Grzegorz , Kryczek Ilona , Wrobel Tomasz , Dlubek Dorota , Klimczak Aleksandra , Jaskula Emilia , Jelen Michal , Lange Andrzej , Kuliczkowski Kazimierz 
Published: April 2020

Abstract
Background: Non-Hodgkin’s lymphomas (nHL) represent heterogenous group of lymphoid malignancies derived from B and T lymphocytes, NK cells or histiocytes. Most of lymphomas are B-cell origin. Lymphoma cells can migrate to other organs and their migration could be linked to chemokines and their receptors. Chemokine receptors are expressed by many cell populations, including lymphoid cells, and their function is mediation of trafficking and localization particularly lymphocytes. CCR5 is predominantly expressed on Th1 cells, but also on dendritic cells, fibroblasts, endothelial and epithelial cells. Up-regulation of CCR5 expression is typical for nonneoplastic leukocytic infiltrates of nodal Hodgkin lymphoma. Its expression has been shown in hairy cell leukemia (HCL) and mantle cell lymphoma (MCL).
Aim: The purpose of this study was to determine CCR5 expression in lymph nodes derived from patients with nHL comparing to control reactive lymph nodes and if there was any correlation between CCR5 expression and proliferation marker Ki-67 and international prognostic index (IPI).
Material and methods: CCR5 gene expression was determined in 37 lymph nodes of lymphoma patients (26 B-cell lymphoma: 12 females and 14 males aged 26–73 years; 4 T-cell lymphoma: males aged 41–81 years; 7 Hodgkin’s lymphoma: 4 females and 3 males aged 21–58 years) and 25 reactive lymph nodes (15 females, 10 males, aged 18–59 years, median age 32 years). Gene expression was determined by the reverse transcription (RT)-polymerase chain reaction method. Scale of expression was 0–3 AU. Statistical analysis was performed using Kruskall-Wallis and Mann-Witney tests (p&lt;0,05).
Results: Most of lymphoma lymph nodes (25/37) showed low CCR5 expression (0–1 AU). In reactive lymph nodes 18/25 had also low CCR5 expression. In B-cell lymphomas high CCR5 expression characterized HCL, Burkitt’s lymphoma and diffuse large B-cell lymphoma nodes. In pts with higher CCR5 expression there was positive correlation with Ki-67 proliferation marker (p=0,016; coefficient = 0,34) and IPI (p=0,047; coefficient = 0,298).
Conclusions: As there is a positive correlation between CCR5 expression and Ki-67 proliferation marker and IPI in non-Hodgkin’s lymphoma lymph nodes CCR5 may be associated with lymphoma progression.
Childhood Crowding, Atopy and Risk of Non-Hodgkin Lymphoma.
Authors: Cozen Wendy , Eric Engels A. , Cerhan James R. , Linet Martha , Bernstein Leslie , Colt Joanne S. , Davis Scott S. , Severson Richard K. , Martinez-Maza Otoniel , Hartge Patricia 
Published: April 2020

Abstract
Subtle differences in immune response may play a role in non-Hodgkin lymphoma (NHL) etiology. Because adult immune response may be influenced by early childhood exposures, we examined the role of childhood crowding, history of atopic disease, and other childhood immune-related exposures on the risk of non-Hodgkin lymphoma in a multi-center case-control study. Interviews were completed with 1,321 cases ascertained from population-based cancer registries in Seattle, Detroit, Los Angeles and Iowa, and with 1,057 frequency-matched controls, selected by random-digit dialing and from the Health Care Financing Administration (HCFA) database. The association between NHL risk in relation to atopy and other exposures was assessed using multivariable logistic regression methods. Most types of allergy were associated with protection from NHL, with hay fever especially protective against all NHL combined (Odds Ratio [OR] = 0.71, 95% confidence interval [CI]= 0.54–0.94), diffuse large B-cell lymphoma [DLBCL] (OR=0.61, 95% CI=0.41–0.91), and follicular lymphoma (OR=0.70, 95% CI=0.45–1.09). A history of eczema increased risk of follicular lymphoma (OR=1.92, 95% CI= 1.08–3.41) but not DLBCL (OR=1.06, 95% CI= 0.55.2.04). Asthma in childhood was not associated with risk of NHL. Risk of DLBCL (OR =1.72, 95% CI=1.17–2.52), but not follicular lymphoma (OR=1.15, 95% CI=0.75–1.76) was elevated for the youngest compared to the oldest of siblings. Neither number of siblings nor years between births of siblings were significantly associated with risk. These results suggest that some immune-related exposures may affect NHL risk.