bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reed-Sternberg Cells Have Shortened Telomere Length.
Authors: Ben-Ezra Jonathan M. , Jackson-Cook Colleen 
Published: April 2020

Abstract
As cells age, the ends of their chromosomes, the telomeres, become shortened. The chromosomal length eventually shortens to a critical point, which is thought to lead to chromosomal instability and/or cell death. Neoplastic cells have increased amounts of telomerase, an enzyme that prevents this shortening; this may be one mechanism by which tumor cells grow. Due to the scarcity of neoplastic Reed-Sternberg cells in tissues of Hodgkin Lymphoma, studies of telomere length and telomerase expression have been difficult and few. These few studies have tended to show an increase in telomerase expression in tissues from Hodgkin Lymphoma. In order to determine telomere length in Reed-Sternberg cells, we performed an immunofluorescence/FISH assay using a PNA pantelomeric probe and a CD30 antibody with which to identify the Reed-Sternberg cells (Am J Pathol 160:1259–68, 2002). Six cases were studied, with patient ages ranging from 18– 51 years. Telomere length was assessed on a semiquantitative scale. Of the six cases, five had evaluable hybridization signal. In these five cases, 53 CD30-positive cells (between 3–20 per case) were studied. In forty cells, the hybridization signal (telomere length) was less than that of surrounding cells, and in 13 it was the same; in no case was telomere length greater in the Reed-Sternberg cell than in surrounding lymphocytes (p&lt; 0.001, Wilcoxon signed ranks test). There was no correlation between the age of the patient or the age of the sample and telomere probe signal intensity/quantity. Similar to epithelial and soft tissue tumors, it appears that the neoplastic cells in Hodgkin Lymphoma have shortened telomere length as compared to the surrounding normal cells.
NK/T Cell Versus Peripheral T Cell Lymphoma: Significant Differences in Clinical Characteristics and Survival.
Authors: Lim Soon-Thye , Gao Fei , Lim Lay-Cheng , Quek Richard , Lim Daryl , Yap Swee-Peng , Loong Susan , Sng Ivy , Tao Miriam 
Published: April 2020

Abstract
Background: To compare the clinico-pathologic characteristics and prognosis of Natural Killer/T cell lymphoma (NK/TL) with peripheral T cell lymphoma (PTCL).
Methods: A total of 556 resident patients (pts) with lymphoma were treated in the departments of medical oncology and hematology in an Asian institution from 2000 to 2005. Of these pts, 71 (12.8%) had NK/TL or PTCL and were included in this analysis. Pathology was centrally reviewed and classified according to the WHO classification.
Results: NK/TL and PTCL comprised of 4.7% (26/556) and 7.9% (45/556) of all cases. Of the PTCL cases, histology was PTCL-NOS in 21, anaplastic large cell in 12 (5 were ALK-1 positive) and angioimmunoblastic T cell in 8 pts. Subcutaneous panniculitis T cell and γ/δ T cell lymphoma accounted for one case each. There were no significant differences between the two groups of pts in terms of sex, performance status, extranodal involvement and LDH level at presentation. However, more patients with NK/TL presented with stage I/II disease (65% vs. 31%, p=0.003). Among pts with NK/TL, 17 (65%) received CHOP-based chemotherapy, 4 received radiation alone and 5 received palliative chemotherapy. In the PTCL group, 39 (87%) received CHOP-based chemotherapy, 2 received radiation alone and 3 received palliative treatment only. Compared to PTCL, NK/TL was associated with a significantly inferior rate of complete remission (27% vs. 58%, p=0.01) and inferior overall survival (5 vs. 28.4 mos, p=0.001). Although age &gt; 60, ECOG ≥ 2, elevated LDH, advanced stage, IPI ≥ 2 and NK/T cell histology were each associated with decreased survival on univariate analysis, only NK/T cell histology and advanced stage were independently associated with decreased survival (see table 1).
Conclusions:
Contrary to expectation, the incidence of PTCL based on WHO classification in this Asian series is not higher than that reported in Western series. Compared to PTCL, the NK/T subtype is associated with a paricularly inferior prognosis and overrides the prognostic significance of IPI. These data suggest that NK/TL should be considered as a seperate entity and should not be considered together with other subtypes of T cell lymphoma in clinical trials.
Table 1. NK/TL vs. PTCL: Univariate and Multivariate Analyses Univariate Analysis Multivariate Analysis Median (yr) P Hazard Ratio 95% CI P Male vs. Female 1.03 vs. Not reached 0.06 0.62 0.28 to 1.40 0.25 Age&lt;60 vs. ≥ 60 2.37 vs. 0.51 0.01 1.41 0.70 to 2.83 0.33 ECOG 0/1 vs. ≥ 2 1.99 vs. 0.36 0.002 1.52 0.63 to 3.65 0.354 LDH normal vs. High Not reached vs. 0.75 0.03 1.29 0.53 to 3.13 0.57 Stage I/II vs. III/IV 1.99 vs. 1.41 0.16 2.91 1.17 to 7.2 0.02 IPI 0/1 vs. ≥ 2 Not Reached vs. 0.42 0.002 2.22 0.82 to 5.99 0.12 PTCL vs. NK/TL 2.37 vs. 0.42 0.001 5.8 2.36 to 14.24 &lt;0.001
JNK Pathway Is Constitutively Activated and Is Required for Survival in Human Mantle-Cell Lymphoma Fresh Cells and Cell-Lines.
Authors: Camara-Clayette Valerie , Vainchenker William , Koscielny Serge , Hermine Olivier , Ribrag Vincent 
Published: April 2020

Abstract
We previously reported that GST-pi, a cellular JNK effector and activator, was strongly expressed in MCL patient’s samples (Clin Cancer Res. 2004). Recently, several primary murine and human B lymphomas were found to constitutively express high levels of activated form of c-jun N-terminal kinase (JNK), a member of the MAP kinase family and that JNK was required for survival in these lymphoid cellular models. To our knowledge, JNK activity has not been assessed in Mantle cell lymphoma cell lines as well as MCL patient’s samples. In vitro kinase assays showed that JNK was constitutively activated in 2 EBV negative cell-lines (JEKO and UPN1) and in 5 MCL patient’s lymphoma cells. JNK and one of its major substrate ATF-2 were found to be constitutively phosphorylated in the same cell-lines and patients MCL samples. JNK inhibition by SP600125, an anthrapyrazolone pharmacological JNK inhibitor impaired cell viability (IC 50: 20 microMol), indicating that JNK exerts a major role in antiapoptotic signals in MCL JEKO and UPN1 cell-lines and fresh human MCL cells. In vitro combination showed that SP600125 and Bortezomib or cytarabine had additive effects in MCL cell-lines and patients fresh lymphoma cells. We also investigated SP600125 activity in a nude model transplanted with UPN1. SP600125 was given IP every 2 days at 40 mg/kg during 10 days, 7 days after UPN1 subcutaneous transplantation. SP600125 therapy significantly delay tumour growth in 6 mice compared to 6 mice who received vehicle alone (DMSO); p=0,001. Thus, JNK pathway activation plays a major role in MCL survival and can be an important target for future therapies.
Up-Regulation of Death Receptor 5 and Bax Translocation Is Necessary To Induce Apoptosis by Sanguinarine in Primary Effusion Lymphoma.
Authors: Hussain Azhar R. , Al-Jomah Naif A. , Siraj Abdul K. , Pulicat Manugaran S. , Al-Hussein Khaled A. , Al-Kuraya Khawla S. , Uddin Shahab 
Published: April 2020

Abstract
Primary effusion lymphoma (PEL) is an aggressive and fatal type of cancer. PEL cells produce a variety of autocrine cytokines and growth factors, which provides cyto-protection against conventional chemotherapeutic agents. In efforts to identify novel approaches to block the proliferation of PEL cells, we found that Sanguinarine, a natural compound isolated from the root plant Sanguinaria canadendid, that is being used as an anti-microbial agent, inhibited cell proliferation and induced apoptosis in a dose dependent manner in several PEL cell lines through a bax-dependent signaling pathway. Five PEL cell lines used in this study were treated with various doses of Sanguinarine ranging between 0.5–4μM inhibited cell proliferation in all the cell lines in a dose dependent manner (BC1 40–97%, BC3 46–93%, BCBL1 11–94%, BCP1 20–97% and HBL6 7–95%). Treatment with varying doses of Sanguinarine also induced apoptosis in all cell lines as determined by cell cycle analysis, annexinV/PI dual staining, TUNEL assay and DNA laddering. Sanguinarine treatment resulted in up-regulation of death receptor 5 (DR5) expression, activation of caspase-8 and Bid leading to Bax conformational changes and translocation to the mitochondrial causing loss of mitochondrial membrane potential as measured by JC1 staining and release of cytochrome c to the cytosole. Sanguinarine induced release of cytochrome c resulted in activation of caspase-3, followed by polyadenosin-5′-diphosphate-ribose polymerase (PARP) cleavage leading to inhibition of proliferation and induction of caspase-dependent apoptosis. Furthermore, pre-treatment of PEL cells with z-VAD-fmk, a universal inhibitor of caspases, abrogated caspase-3 and PARP activation and prevented cell death induced by Sanguinarine. Inhibitor of apoptosis proteins (IAPs), play an important role in protecting cells against apoptosis through their direct action on caspases-9 and -3. Treatment of PEL cells with Sanguinarine down-regulated the expression of IAPs; XIAP, cIAP1 and cIAP2. Taken altogether, our findings suggest that Sanguinarine induces apoptosis via up-regulation of DR5, activation of Bax in a caspase-dependent pathway and down-regulation of IAPs. These results provide the molecular basis and preliminary data for new treatment strategies that may incorporate Sanguinarine in regimens for primary effusion lymphoma treatment.
Chlorambucil Induced Angioedema of the Tongue in a Patient with Lymphoma.
Authors: Shojania A. Majid 
Published: April 2020

Abstract
A Caucasian female, born in 1941, was first seen in November 2002 because of tiredness, weight loss and splenomegaly. She was taking glyburide, procylidine and venlafaxine for diabetes, parkinsonism and depression. Physical examination, revealed marked splenomegaly but no lymphadenopathy. Flowcytometry of peripheral blood showed a monoclonal B cell lymphoproliferative disorder consistent with marginal zone lymphoma. She was treated with chlorambucil 6 mg daily and prednisone 25 mg daily. She responded well to therapy. Chemotherapy was discontinued in December 2003. In April 2005 she was admitted to the hospital with pneumonia. She had pancytopenia and marked splenomegaly. Bone marrow apirate showed infiltration with marginal zone lymphoma cells. She was prescribed Chlorambucil 6 mg daily for management of her recurrent lymphoma. She took her first 6 mg of Chlorambucil at 8:00 PM of May 18, 2005 and woke up around 5:30 AM with grossly swollen tongue. She was brough to Emergency ward at 06:45 hr with grossly swollen, tender tongue protrudinng form her widely opened mouth. Angioedema of the tongue was diagnosed and she was given epinephrin, IV Benadryl, Solumedrol and morphine. By 10:00 hr, she was in moderate respiratory distress. She was taken to OR at 10:20 for urgent intubation or tracheotomy. Endoscopy revealed ++ oropharyngeal and supraglotic edema. A nasotracheal tube was inserted at 11:00 hr. The picture included was taken one hour after intubation.(16 hrs after taking chlorambucil). She was given Solumedrol 125 mg IV Q 12 hr. By 24 hours after intubation her tongue had receded into her mouth and she was extubated. Her serum C1 inhibitor was 0.13 g/L (normal 0.15–0.35) and functional C1 esterase inhibitor was 87% (normal &gt;67%). Immunoglobulines, C3 & C4 were normal. Her lymphoma was treated with 6 courses of R-CVP regimen. She has not received any more chlorambucil and she has not had any more angioedema or anaphylactic reaction of any kind. In May 2005 her C1 inhibitor was 0.38 g/L and functional C1 esterase inhibitor was 96%.
Discussion: on the day before experiencing angioedema of the tongue, she had not taken any unusual food or any other new medication. The time sequence and subsequent course of this case strongly suggest that the angioedema of the tongue was due to Chlorambucil. The literature does not show any report of chlorambucil induced angioedema. However, angioedema is listed as one of the adverse reactions of Chlorambuci both in AHFS Drug Information and in Compendium of Pharmaceuticals and Specialities. Following communication with GlaskoSmithKline, the manufacturer of Chlorambucil, I was told that, they are not aware of any published report, but they have reports of angioedema induced by Chlorambucil in their file. I was told that they are not in position to reveal the number of such reactions.
Figure Figure
Cutaneous Lymphomas: Single Institution Experience in Lima-Peru.
Authors: Beltrán-Gárate Brady E. , Malaga José , Portugal Karen , Morales Domingo , Riva Luis , de Mendoza Fernando Hurtado , Castillo-Aguirre Jorge , Quiñones Pilar , Carrasco-Yalan Antonio A. 
Published: April 2020

Abstract
Background: The clinicopathologic characteristics of malignant lymphomas may vary according to geography. We previously described Adult T -cell leukaemia/lymphoma (ATLL) cases associated with human T-cell lymphotropic virus type-I (HTLV-I) in their different clinical presentation: acute, lymphomatous, chronic and smoldering and the recently primary cutaneous subtype in Peru (EHA2001: abstract 129). The aim of this study is to determine the relative frequency of cutaneous lymphomas and evaluate the clinical relevance of the new WHO/EORTC classification in a General Hospital in Lima-Peru
Methods: We conducted a clinicopathologic retrospective study of primary cutaneous lymphomas diagnosed from 1997 to 2004 in our General Hospital. Clinical records, haematoxylin & eosin-stained slides and immunohistochemical stains from 78 patients were reviewed. HTLV-1 serology was made using ELISA and Western Blot method. The statistical method was descriptive and survival was calculated using the Kaplan-Meier method.
Results: The mean age at time of presentation was 62 years and the female/male ratio 1,5:1. T-cell lymphomas were 88.6% and 11.4% were B-cell lymphomas. Eight-six percent (67/78) were primary cutaneous lymphomas and fourteen percent (11/78) were secondary cutaneous lymphomas. The most frequent primary cutaneous lymphomas was mycosis fungoides (MF): 44.7% (30/67); cutaneous / smoldering ATLL sutypes included 13/67 (19.4%) patients; unspecified peripheral T-cell lymphoma 4/67 (6%), lymphomatoid papulosis 2/67 (3%), leg-type diffuse large B-cell lymphoma 2/67 (3%), diffuse large B-cell lymphoma 2/67 (3%), subcutaneous panniculitis-like T-cell lymphoma 2/67 (3%), one case of the following lymphomas: anaplastic large cell, Sézary syndrome, nasal type extranodal NK/T-cell lymphoma, marginal zone B-cell lymphoma, follicle center lymphoma and intravascular lymphoma; finally unclassifiable lymphomas 5/67 (7.4%). Most frequent secondary cutaneous lymphomas were acute and lymphomatous subtypes of ATLL with 72% of the cases. Five-years overall survival for MF was 77%. The 5-years overall survival for primary cutaneous ATLL lymphomas was 18% and 0% for the secondary cutaneous ATLL group.
Conclusions: In this retrospective analysis, both ATLL and MF are the most frequent cutaneous lymphomas in our General Hospital. ATLL has a poor overall survival.
BCL6 Rearrangement Detected by FISH Analysis Is a Poor Prognostic Factor in the “Non-Germinal Center Phenotype” of Diffuse Large B-Cell Lymphoma.
Authors: Takizawa Jun , Aoki Sadao , Momoi Akihito , Kitajima Toshiki , Higashimura Masutaka , Nakamura Naoya , Aizawa Yoshifusa 
Published: April 2020

Abstract
Background: Diffuse large B-cell lymphoma (DLBCL), which is the most common type of adult non-Hodgkin lymphoma, is considered to be heterogeneous in cytogenetics, immunophenotype and clinical feature. As the results of gene expression profiling, DLBCL can be divided into prognostically significant 3 subgroups of germinal center B-like (GCB), activated B-like and type 3. Chromosomal translocations affecting the BCL6 locus at the 3q27 locus are common in DLBCL, however, the prognostic significance of BCL6 rearrangement is still controversial.
Methods: Twenty-six cases of DLBCL were examined with interphase fluorescence in situ hybridization (FISH) on touch preparations of lymph nodes using LSI BCL6 dual color probes (Vysis) for the incidence of BCL6 rearrangement and immunohistochemistry on paraffin section using CD10, BCL6 and MUM1 for subclassfying “GCB phenotype” and “non-GCB phenotype”. The correlation of BCL6 rearrangement with survival was investigated in two subgroups of DLBCL.
Results: Of the 26 DLBCL cases, 6 cases (23%) were considered GCB phenotype and 20 cases (77%) non-GCB phenotype. BCL6 rearrangements were detected in 2 of 6 cases (33%) with GCB phenotype and 9 of 20 (45%) with non-GCB phenotype (total 11/26, 42%). ALL 6 cases with the GCB phenotype achieved sustained complete remission after chemotherapy and are alive. On the other hand, complete remission rate was 22% for the cases with BCL6 rearrangement but 73% for the cases without BCL6 rearrangement in the non-GCB phenotype (p=0.069). BCL6 rearrangement had a significant adverse effect on progression free survival within the non-GCB phenotype (P=0.016), but there was no significant correlation between BCL6 rearrangement and overall survival.
Conclusion: FISH-based technique of the BCL6 rearrangements using touch preparations of lymph nodes could be developed for the retrospective analysis on survival. BCL6 rearrangement showed a poor prognostic effect particular in the non-GCB subgroup of DLBCL.
Overall survival Overall survival Progression free survival Progression free survival
Incidence, Clinical Characteristics and Survival of Malignant Lymphomas in the Province of Modena (Italy); a Population-Based Study.
Authors: Luminari Stefano , Cesaretti Marina , Rashid Ivan , Pennese Elsa , Mammi Caterina , Montanini Antonella , Barbolini Elisa , Bellei Monica , Marcheselli Luigi , Partesotti Giovanni , Bari Alessia , Maiorana Antonio , Artusi Tullio , Federico Massimo 
Published: April 2020

Abstract
The incidence of lymphomas has increased in many parts of the world in recent decades. We conducted a population-based study of peripheral lymphoma (PL) in the province of Modena (Italy). According to the international classification for lymphomas (WHO/ICD-O-3) we evaluated incidence patterns and time trends of 1,582 cases of PLs diagnosed between 1997–2003, also providing details of clinical characteristics, treatment and outcome of different entities. World Age Standardized Rates (ASR) varied substantially among lymphoid neoplasm subtypes. Overall, ASR (per 100,000) was 13.4 for B-cell lymphomas (16.5 and 10.6 for males and females respectively), 2.2 for T-cell lymphomas (3.1 and 1.5) and 3.4 for Hodgkin lymphoma. Among B-NHL the highest ASR was observed for Diffuse large B-cell lymphoma (DLBCL, 4.8) and Small lymphocytic lymphoma (CLL/SLL, 3.3). Among T-cell lymphomas, ASR was 1.4 for Mycosis fungoides/Sezary syndrome (MF/SS) and 0.4 for both Peripheral T-cell lymphoma (PTCL) and Anaplastic large cell lymphoma (ALCL). The overall annual percent change (APC) of the World ASR was 1.62 (C.I.95%: −4.32; 7.93). Extranodal (EN) involvement was observed in 49% of cases; a diagnosis of Primary EN lymphoma (PENL) was confirmed in 27.8% of cases. In addition to MF/SS, the most frequently reported PENL were marginal zone lymphomas (MZL) and DLBCL. The documented five years Overall Survival (OS) for the whole series was 61.9%, being 61.7%, 55.3% and 83% for B-NHL, T-NHL and HL, respectively. These data confirm an overall improvement when compared with available historical controls for the main European countries. In addition, using period analysis we could estimate more up-to-date survival data within our studied series (all patients vs those diagnosed after 2002): survival of patients with MZL, DLBCL and HL strongly improved during the study period. Among different lymphoma subtypes, patients with Hairy cell leukemia (HCL), HL and MF/SS had the best survival with 5-year OS of 94%, 83% and 82%, respectively. In particular, for HCL and MF/SS the analysis of the Relative Survival suggested that there was no substantial difference in survival compared with healthy population. Our study provides a comprehensive description of both epidemiological and clinical features of PL in the province of Modena, recognizing in a population-based approach, major advances in the curability of some histological subtypes.
BCL2 Expression Is a Prognostic Marker for the Activated B-Cell-Like Type of Diffuse Large B-Cell Lymphoma.
Authors: Chiattone Carlos , Carvalho Marineide P. , Paes Roberto P. , Ribeiro Karina C.B. , Soares Fernando 
Published: April 2020

Abstract
Diffuse large B-cell lymphoma (DLBCL) is heterogeneous both clinically and morphologically reflecting a mixture of underlying biologic or genetic differences. Therefore, it is important to identify at diagnosis biological markers which permit determination of subgroups with favorable or unfavorable evolution. The goal of this study was to evaluate the impact of BCL-2 tumor expression on overall survival (OS) in germinal center B-cell (GCB) and non-GCB subgroup.
Patients and Methods. Seventy-four untreated pts (median age: 58 yrs: 36M/34F) 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. Tumor expression of BCL-2 (cut off 10%), by TMA, was seen in 47.3% (35/74) and was associated with a worse OS (44.7%) (p=0.038). There was no significant correlation between BCL-2 protein expression and OS (p=0.587) OS (p=0.587), whereas for the group non-GCB was associated with a worse OS (p = 0.017).
Conclusion: The immunohistochemical expression of BCL- 2 are able to identify for the GCB and non-GCB subtypes of DLBCL outcome.