Ran GTPase-activating protein 1 is a therapeutic target in diffuse large B-cell lymphoma.

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Kung-Chao Chang

Full Text Available Lymphoma-specific biomarkers contribute to therapeutic strategies and the study of tumorigenesis. Diffuse large B-cell lymphoma (DLBCL is the most common type of malignant lymphoma. However, only 50% of patients experience long-term survival after current treatment; therefore, developing novel therapeutic strategies is warranted. Comparative proteomic analysis of two DLBCL lines with a B-lymphoblastoid cell line (LCL showed differential expression of Ran GTPase-activating protein 1 (RanGAP1 between them, which was confirmed using immunoblotting. Immunostaining showed that the majority of DLBCLs (92%, 46/50 were RanGAP1(+, while reactive lymphoid hyperplasia (n = 12 was RanGAP1(+ predominantly in germinal centers. RanGAP1 was also highly expressed in other B-cell lymphomas (BCL, n = 180 with brisk mitotic activity (B-lymphoblastic lymphoma/leukemia: 93%, and Burkitt lymphoma: 95% or cell-cycle dysregulation (mantle cell lymphoma: 83%, and Hodgkin's lymphoma 91%. Interestingly, serum RanGAP1 level was higher in patients with high-grade BCL (1.71 ± 2.28 ng/mL, n = 62 than in low-grade BCL (0.75 ± 2.12 ng/mL, n = 52 and healthy controls (0.55 ± 1.58 ng/mL, n = 75 (high-grade BCL vs. low-grade BCL, p = 0.002; high-grade BCL vs. control, p < 0.001, Mann-Whitney U test. In vitro, RNA interference of RanGAP1 showed no effect on LCL but enhanced DLBCL cell death (41% vs. 60%; p = 0.035 and cell-cycle arrest (G0/G1: 39% vs. 49%, G2/M: 19.0% vs. 7.5%; p = 0.030 along with decreased expression of TPX2 and Aurora kinases, the central regulators of mitotic cell division. Furthermore, ON 01910.Na (Estybon, a multikinase inhibitor induced cell death, mitotic cell arrest, and hyperphosphorylation of RanGAP1 in DLBCL cell lines but no effects in normal B and T cells. Therefore, RanGAP1 is a promising marker and therapeutic target for aggressive B-cell lymphoma, especially DLBCL.

ONC201 induces cell death in pediatric non-Hodgkin's lymphoma cells.

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Talekar, Mala K; Allen, Joshua E; Dicker, David T; El-Deiry, Wafik S

2015-08-03

ONC201/TIC10 is a small molecule initially discovered by its ability to coordinately induce and activate the TRAIL pathway selectively in tumor cells and has recently entered clinical trials in adult advanced cancers. The anti-tumor activity of ONC201 has previously been demonstrated in several preclinical models of cancer, including refractory solid tumors and a transgenic lymphoma mouse model. Based on the need for new safe and effective therapies in pediatric non-Hodgkin's lymphoma (NHL) and the non-toxic preclinical profile of ONC201, we investigated the in vitro efficacy of ONC201 in non-Hodgkin's lymphoma (NHL) cell lines to evaluate its therapeutic potential for this disease. ONC201 caused a dose-dependent reduction in the cell viability of NHL cell lines that resulted from induction of apoptosis. As expected from prior observations, induction of TRAIL and its receptor DR5 was also observed in these cell lines. Furthermore, dual induction of TRAIL and DR5 appeared to drive the observed apoptosis and TRAIL expression was correlated linearly with sub-G1 DNA content, suggesting its potential role as a biomarker of tumor response to ONC201-treated lymphoma cells. We further investigated combinations of ONC201 with approved chemotherapeutic agents used to treat lymphoma. ONC201 exhibited synergy in combination with the anti-metabolic agent cytarabine in vitro, in addition to cooperating with other therapies. Together these findings indicate that ONC201 is an effective TRAIL pathway-inducer as a monoagent that can be combined with chemotherapy to enhance therapeutic responses in pediatric NHL.

Tumor dedifferentiation: diagnostic and therapeutic implications

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Abhimanyu Jha

2017-09-01

Full Text Available Some of the neoplasm especially malignant tumors are notorious in masquerading their cell of origin because of additional mutations which drives them to differentiate into unusual phenotype. This is implicated to a phenomenon of tumor dedifferentiation which can mislead into inappropriate categorization and therapy. Dedifferentiation is well recognized in sarcomas such as liposarcoma, chondrosarcoma and MPNST. However, it can also develop in carcinomas, melanomas and lymphomas at initial diagnosis, following therapy or at recurrence.  The phenomenon has been reported in both primary tumors as well as at metastatic foci. A correct and early pathological identification of this phenomenon might profoundly help in guiding appropriate therapy. Clinical and radiological findings, immunohistochemistry and genetic analysis are often required for correct lineage identification of these tumors.

17-DMAG in Treating Patients With Metastatic or Unresectable Solid Tumors or Lymphomas

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2013-01-24

Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Stage IV Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Waldenstr

Inflammatory myofibroblastic tumor of inguinal lymph nodes, simulating lymphoma

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Akansha Gandhi

2015-01-01

Full Text Available Multiple enlarged lymph nodes in an elderly female patient can have varied etiologies as well as histologic pictures. We are presenting the case of a 53-year-old female who presented with inguinal lymphadenopathy with fever, which was clinically misconstrued as lymphoma. Cytology could not exclude a lymphoma. Histology led to the unusual diagnosis of inflammatory myofibroblastic tumor of lymph node in this case. Inflammatory myofibroblastic tumor of the lymph node is a rare, distinctive reactive proliferative pattern in the lymph node which involves proliferation of the connective tissue elements of the lymph node, admixed with lymphocytes, plasma cells, eosinophils, and histiocytes. Multiple etiologic agents have been suggested in existing literature. Despite extensive search, no definite attributable cause could be sought. It is now widely accepted that inflammatory pseudotumor of the lymph node is a non-neoplastic proliferation which has a benign clinical course and excellent prognosis after surgical resection.

Systematic analysis of a xenograft mice model for KSHV+ primary effusion lymphoma (PEL.

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Lu Dai

Full Text Available Kaposi's sarcoma-associated herpesvirus is the causative agent of primary effusion lymphoma (PEL, which arises preferentially in the setting of infection with human immunodeficiency virus (HIV. Even with standard cytotoxic chemotherapy, PEL continues to cause high mortality rates, requiring the development of novel therapeutic strategies. PEL xenograft models employing immunodeficient mice have been used to study the in vivo effects of a variety of therapeutic approaches. However, it remains unclear whether these xenograft models entirely reflect clinical presentations of KSHV(+ PEL, especially given the recent description of extracavitary solid tumor variants arising in patients. In addition, effusion and solid tumor cells propagated in vivo exhibit unique biology, differing from one another or from their parental cell lines propagated through in vitro culture. Therefore, we used a KSHV(+ PEL/BCBL-1 xenograft model involving non-obese diabetic/severe-combined immunodeficient (NOD/SCID mice, and compared characteristics of effusion and solid tumors with their parent cell culture-derived counterparts. Our results indicate that although this xenograft model can be used for study of effusion and solid lymphoma observed in patients, tumor cells in vivo display unique features to those passed in vitro, including viral lytic gene expression profile, rate of solid tumor development, the host proteins and the complex of tumor microenvironment. These items should be carefully considered when the xenograft model is used for testing novel therapeutic strategies against KSHV-related lymphoma.

Pathophysiological aspects and therapeutic approaches of tumoral osteolysis and hypercalcemia.

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Bonjour, J P; Rizzoli, R

1989-01-01

Malignant tumors can affect the integrity of the skeletal tissue and the homeostasis of the two main components of bone mineral, calcium (Ca) and inorganic phosphate (Pi). Various tumoral cell products can increase bone resorption by influencing the number of osteoclasts and/or their activity. These tumoral products could act either directly on bone cells of the osteoblastic or osteoclastic lineages, or indirectly by influencing cells secreting osteotropic factors, such as interleukin-1, tumor necrosis factors, transforming growth factors, and colony-stimulating factor. Among the classical calciotropic hormones, 1,25-dihydroxyvitamin D3 could be implicated in lymphoma. In hypercalcemia of malignancy, an increase in bone resorption is observed in most patients. However, in many cases an increased tubular reabsorption of Ca has been documented as well. This phenomenon when present after adequate rehydration is probably due to the secretion by the tumoral cells of a parathyroid hormone-related peptide (PTHrP). This factor has been recently identified as a protein containing 141 amino acids. This protein or some very close analogs have been shown to be secreted by lung, kidney and also breast carcinoma. Besides increasing bone resorption and stimulating tubular reabsorption of Ca, PTHrP also selectively decreases the tubular reabsorption of Pi, an action that may explain the hypophosphatemia observed in some types of neoplasm. Therapeutically, administration of antiresorbing agents such as clodronate or other bisphosphonates can normalize the increased osteolysis and, if present, the associated elevation in the plasma level of Ca in most cancer patients. However in some cases, wherein the prevailing hypercalcemic mechanism is due to an enhancement in the tubular reabsorption of Ca, other therapeutic means should be associated with the antiosteolytic bisphosphonate therapy.

Brentuximab Vedotin Treatment for Primary Refractory Hodgkin Lymphoma

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Hung-Bo Wu

2013-01-01

Full Text Available Up to 40% of patients with advanced Hodgkin lymphoma (HL become refractory or relapsed after current standard chemotherapy, among which primary refractory HL confers a particularly poor outcome. With intensive salvage chemotherapy and autologous stem cell transplantation, the long-term remission rate for these patients was only 30%, but more selective treatments with higher therapeutic index are needed. We report the experience of using a new anti-CD30 immunotoxin, brentuximab vedotin, in salvage treatment of a 30-year-old woman with primary refractory Hodgkin lymphoma. The patient presented with SVC syndrome due to the bulky mediastinal tumor and was confirmed to have classical Hodgkin lymphoma, nodular sclerosis type, stage IIIA. The tumor responded to induction chemotherapy transiently, but local progression was noted during subsequent cycles of treatment. Salvage radiotherapy to the mediastinal tumor, obtained no remission but was followed by rapid in-field progression and then lung metastasis. She declined stem cell transplantation and received salvage brentuximab vedotin (BV therapy, which induced dramatic shrinkage of tumor without significant side effects. Serial followup of PET/CT imaging confirmed a rapid and continuous complete remission for 12 months. Although durability of the remission needs further observation, this case illustrates the excellent efficacy of brentuximab vedotin in primary refractory Hodgkin lymphoma.

Malignant lymphomas (ML and HIV infection in Tanzania

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Mwakigonja Amos R

2008-06-01

Full Text Available Abstract Background HIV infection is reported to be associated with some malignant lymphomas (ML so called AIDS-related lymphomas (ARL, with an aggressive behavior and poor prognosis. The ML frequency, pathogenicity, clinical patterns and possible association with AIDS in Tanzania, are not well documented impeding the development of preventive and therapeutic strategies. Methods Sections of 176 archival formalin-fixed paraffin-embedded biopsies of ML patients at Muhimbili National Hospital (MNH/Muhimbili University of Health and Allied Sciences (MUHAS, Tanzania from 1996–2001 were stained for hematoxylin and eosin and selected (70 cases for expression of pan-leucocytic (CD45, B-cell (CD20, T-cell (CD3, Hodgkin/RS cell (CD30, histiocyte (CD68 and proliferation (Ki-67 antigen markers. Corresponding clinical records were also evaluated. Available sera from 38 ML patients were screened (ELISA for HIV antibodies. Results The proportion of ML out of all diagnosed tumors at MNH during the 6 year period was 4.2% (176/4200 comprising 77.84% non-Hodgkin (NHL including 19.32% Burkitt's (BL and 22.16% Hodgkin's disease (HD. The ML tumors frequency increased from 0.42% (1997 to 0.70% (2001 and 23.7% of tested sera from these patients were HIV positive. The mean age for all ML was 30, age-range 3–91 and peak age was 1–20 years. The male:female ratio was 1.8:1. Supra-diaphragmatic presentation was commonest and histological sub-types were mostly aggressive B-cell lymphomas however, no clear cases of primary effusion lymphoma (PEL and primary central nervous system lymphoma (PCNSL were diagnosed. Conclusion Malignant lymphomas apparently, increased significantly among diagnosed tumors at MNH between 1996 and 2001, predominantly among the young, HIV infected and AIDS patients. The frequent aggressive clinical and histological presentation as well as the dominant B-immunophenotype and the HIV serology indicate a pathogenic association with AIDS. Therefore

Malignant lymphomas (ML) and HIV infection in Tanzania.

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Mwakigonja, Amos R; Kaaya, Ephata E; Mgaya, Edward M

2008-06-10

HIV infection is reported to be associated with some malignant lymphomas (ML) so called AIDS-related lymphomas (ARL), with an aggressive behavior and poor prognosis. The ML frequency, pathogenicity, clinical patterns and possible association with AIDS in Tanzania, are not well documented impeding the development of preventive and therapeutic strategies. Sections of 176 archival formalin-fixed paraffin-embedded biopsies of ML patients at Muhimbili National Hospital (MNH)/Muhimbili University of Health and Allied Sciences (MUHAS), Tanzania from 1996-2001 were stained for hematoxylin and eosin and selected (70) cases for expression of pan-leucocytic (CD45), B-cell (CD20), T-cell (CD3), Hodgkin/RS cell (CD30), histiocyte (CD68) and proliferation (Ki-67) antigen markers. Corresponding clinical records were also evaluated. Available sera from 38 ML patients were screened (ELISA) for HIV antibodies. The proportion of ML out of all diagnosed tumors at MNH during the 6 year period was 4.2% (176/4200) comprising 77.84% non-Hodgkin (NHL) including 19.32% Burkitt's (BL) and 22.16% Hodgkin's disease (HD). The ML tumors frequency increased from 0.42% (1997) to 0.70% (2001) and 23.7% of tested sera from these patients were HIV positive. The mean age for all ML was 30, age-range 3-91 and peak age was 1-20 years. The male:female ratio was 1.8:1. Supra-diaphragmatic presentation was commonest and histological sub-types were mostly aggressive B-cell lymphomas however, no clear cases of primary effusion lymphoma (PEL) and primary central nervous system lymphoma (PCNSL) were diagnosed. Malignant lymphomas apparently, increased significantly among diagnosed tumors at MNH between 1996 and 2001, predominantly among the young, HIV infected and AIDS patients. The frequent aggressive clinical and histological presentation as well as the dominant B-immunophenotype and the HIV serology indicate a pathogenic association with AIDS. Therefore, routine HIV screening of all malignant lymphoma

MicroRNAs in mantle cell lymphoma

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Husby, Simon; Geisler, Christian; Grønbæk, Kirsten

2013-01-01

Mantle cell lymphoma (MCL) is a rare and aggressive subtype of non-Hodgkin lymphoma. New treatment modalities, including intensive induction regimens with immunochemotherapy and autologous stem cell transplant, have improved survival. However, many patients still relapse, and there is a need...... for novel therapeutic strategies. Recent progress has been made in the understanding of the role of microRNAs (miRNAs) in MCL. Comparisons of tumor samples from patients with MCL with their normal counterparts (naive B-cells) have identified differentially expressed miRNAs with roles in cellular growth...

Ocular adnexal marginal zone lymphoma of mucosa-associated lymphoid tissue.

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Kalogeropoulos, Dimitrios; Papoudou-Bai, Alexandra; Kanavaros, Panagiotis; Kalogeropoulos, Chris

2018-05-01

Ocular adnexal lymphomas are a group of heterogeneous neoplasms representing approximately 1-2% of non-Hodgkin lymphomas and 8% of extranodal lymphomas. The incidence of primary ocular adnexal lymphoid tumors has raised over the last decades, and this could be probably attributed to the more sophisticated diagnostic techniques. Due to the wide spectrum of clinical manifestations, ocular tissue biopsy is important in order to set a precise diagnosis based on histological, immunophenotypical and, in some cases, molecular findings. The most common subtype, which may account for up to 80% of primary ocular adnexal lymphomas, is extranodal marginal zone lymphoma (EMZL) of mucosa-associated lymphoid tissue. This lymphoma is usually asymptomatic in the early phase of the disease causing a delay in the final diagnosis and prompt therapy. The pathogenesis of a proportion of these tumors has been linked to chronic inflammatory stimulation from specific infectious factors (e.g., Chlamydia psittaci) or to autoimmunity. The further improvement in diagnostic methods and the further understanding of the pathogenesis of ocular adnexal EMZL may contribute to the establishment of a more successful multidisciplinary therapeutic planning.

The emerging pathogenic and therapeutic importance of the anaplastic lymphoma kinase gene.

LENUS (Irish Health Repository)

Kelleher, Fergal C

2012-02-01

The anaplastic lymphoma kinase gene (ALK) is a gene on chromosome 2p23 that has expression restricted to the brain, testis and small intestine but is not expressed in normal lymphoid tissue. It has similarity to the insulin receptor subfamily of kinases and is emerging as having increased pathologic and potential therapeutic importance in malignant disease. This gene was originally established as being implicated in the pathogenesis of rare diseases including inflammatory myofibroblastic tumour (IMT) and ALK-positive anaplastic large cell lymphoma, which is a subtype of non-Hodgkin\\'s lymphoma. Recently the number of diseases in which ALK is implicated in their pathogenesis has increased. In 2007, an inversion of chromosome 2 involving ALK and a fusion partner gene in a subset of non-small cell lung cancer was discovered. In 2008, publications emerged implicating ALK in familial and sporadic cases of neuroblastoma, a childhood cancer of the sympatho-adrenal system. Chromosomal abnormalities involving ALK are translocations, amplifications or mutations. Chromosomal translocations are the longest recognised ALK genetic abnormality. When translocations occur a fusion gene is created between ALK and a gene partner. This has been described in ALK-positive anaplastic large cell lymphoma in which ALK is fused to NPM (nucleolar protein gene) and in non-small cell lung cancer where ALK is fused to EML4 (Echinoderm microtubule-associated protein 4). The most frequently described partner genes in inflammatory myofibroblastic tumour are tropomyosin 3\\/4 (TMP3\\/4), however in IMTs a diversity of ALK fusion partners have been found, with the ability to homodimerise a common characteristic. Point mutations and amplification of the ALK gene occur in the childhood cancer neuroblastoma. Therapeutic targeting of ALK fusion genes using tyrosine kinase inhibition, vaccination using an ALK specific antigen and treatment using viral vectors for RNAi are emerging potential therapeutic

[Mantle cell lymphoma: Towards a personalized therapeutic strategy?].

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Navarro Matilla, Belén; García-Marco, José A

2015-06-22

Mantle cell lymphoma (MCL) is a clinically heterogeneous non-Hodgkin lymphoma with an aggressive clinical behaviour and short survival in some cases and an indolent course in others. Advances in the biology and pathogenesis of MCL have unveiled several genes involved in deregulation of cell cycle checkpoints and the finding of subclonal populations with specific recurrent mutations (p53, ATM, NOTCH2) with an impact on disease progression and refractoriness to treatment. Prognostic stratification helps to distinguish between indolent and aggressive forms of MCL. Currently, younger fit patients benefit from more intensive front line chemotherapy regimens and consolidation with autologous transplantation, while older or frail patients are treated with less intensive regimens and rituximab maintenance. For relapsing disease, the introduction of bortezomib and lenalidomide containing regimens and B-cell receptor pathway inhibitors such as ibrutinib and idelalisib in combination with immunochemotherapy have emerged as therapeutic agents with promising clinical outcomes. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Adult high-grade B-cell lymphoma with Burkitt lymphoma signature: genomic features and potential therapeutic targets.

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Bouska, Alyssa; Bi, Chengfeng; Lone, Waseem; Zhang, Weiwei; Kedwaii, Ambreen; Heavican, Tayla; Lachel, Cynthia M; Yu, Jiayu; Ferro, Roberto; Eldorghamy, Nanees; Greiner, Timothy C; Vose, Julie; Weisenburger, Dennis D; Gascoyne, Randy D; Rosenwald, Andreas; Ott, German; Campo, Elias; Rimsza, Lisa M; Jaffe, Elaine S; Braziel, Rita M; Siebert, Reiner; Miles, Rodney R; Dave, Sandeep; Reddy, Anupama; Delabie, Jan; Staudt, Louis M; Song, Joo Y; McKeithan, Timothy W; Fu, Kai; Green, Michael; Chan, Wing C; Iqbal, Javeed

2017-10-19

The adult high-grade B-cell lymphomas sharing molecular features with Burkitt lymphoma (BL) are highly aggressive lymphomas with poor clinical outcome. High-resolution structural and functional genomic analysis of adult Burkitt lymphoma (BL) and high-grade B-cell lymphoma with BL gene signature (adult-molecularly defined BL [mBL]) revealed the MYC-ARF-p53 axis as the primary deregulated pathway. Adult-mBL had either unique or more frequent genomic aberrations (del13q14, del17p, gain8q24, and gain18q21) compared with pediatric-mBL, but shared commonly mutated genes. Mutations in genes promoting the tonic B-cell receptor (BCR)→PI3K pathway ( TCF3 and ID3 ) did not differ by age, whereas effectors of chronic BCR→NF-κB signaling were associated with adult-mBL. A subset of adult-mBL had BCL2 translocation and mutation and elevated BCL2 mRNA and protein expression, but had a mutation profile similar to mBL. These double-hit lymphomas may have arisen from a tumor precursor that acquired both BCL2 and MYC translocations and/or KMT2D ( MLL2 ) mutation. Gain/amplification of MIR17HG and its paralogue loci was observed in 50% of adult-mBL. In vitro studies suggested miR-17∼92 's role in constitutive activation of BCR signaling and sensitivity to ibrutinib. Overall integrative analysis identified an interrelated gene network affected by copy number and mutation, leading to disruption of the p53 pathway and the BCR→PI3K or NF-κB activation, which can be further exploited in vivo by small-molecule inhibitors for effective therapy in adult-mBL.

[A morphometric analysis of the nuclei and nucleoli in tumor cells in lymphogranulomatosis, diffuse large B-cell lymphoma and anaplastic large cell lymphoma].

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Gorgidze, L A; Vorob'ev, I A

2009-01-01

To make a comparative morphometric analysis of the nuclei and nucleoli of tumor cells in lymphogranulomatosis (LGM), diffuse large B-cell lymphoma (DLBCL) and anaplastic large cell lymphoma (ALCL) for differential diagnosis of these lymphomas. Biopsy material (lymph node biopsies) was frozen in hexane, fixed and stained, then microscopic pictures were made. Mean area of tumor cell nuclei in LGM was 97.25 +/- 68.77 mcm2, in DLBCL and ALCL--55.89 +/- 20.13 mcm2 and 70.31 +/- 34.64 mcm2, respectively. The area differences were significant (p nucleoli of the former are larger than those of the latter. Mean area of the nucleoli in DLBCL was 3.05 +/- 1.58, in ALCL--5.53 +/- 4.94 mcm2. The differences are significant (p Nucleoli in Hodgkin 's cells are significantly larger than those in the tumor cells in ALCL and DLBCL and the nucleoli with the area more than 12 mcm2 can be used in differential diagnosis between LGM and DLBCL but not between LGM and ALCL.

Pan-SRC kinase inhibition blocks B-cell receptor oncogenic signaling in non-Hodgkin lymphoma.

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Battistello, Elena; Katanayeva, Natalya; Dheilly, Elie; Tavernari, Daniele; Donaldson, Maria C; Bonsignore, Luca; Thome, Margot; Christie, Amanda L; Murakami, Mark A; Michielin, Olivier; Ciriello, Giovanni; Zoete, Vincent; Oricchio, Elisa

2018-05-24

In diffuse large B-cell lymphoma (DLBCL), activation of the B-cell receptor (BCR) promotes multiple oncogenic signals, which are essential for tumor proliferation. Inhibition of the Bruton's tyrosine kinase (BTK), a BCR downstream target, is therapeutically effective only in a subgroup of patients with DLBCL. Here, we used lymphoma cells isolated from patients with DLBCL to measure the effects of targeted therapies on BCR signaling and to anticipate response. In lymphomas resistant to BTK inhibition, we show that blocking BTK activity enhanced tumor dependencies from alternative oncogenic signals downstream of the BCR, converging on MYC upregulation. To completely ablate the activity of the BCR, we genetically and pharmacologically repressed the activity of the SRC kinases LYN, FYN, and BLK, which are responsible for the propagation of the BCR signal. Inhibition of these kinases strongly reduced tumor growth in xenografts and cell lines derived from patients with DLBCL independent of their molecular subtype, advancing the possibility to be relevant therapeutic targets in broad and diverse groups of DLBCL patients. © 2018 by The American Society of Hematology.

A novel xenograft model of cutaneous T-cell lymphoma

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Krejsgaard, Thorbjørn; Kopp, Katharina; Ralfkiaer, Elisabeth

2010-01-01

Cutaneous T-cell lymphomas (CTCLs) are characterized by accumulation of malignant T cells in the skin. Early disease resembles benign skin disorders but during disease progression cutaneous tumors develop, and eventually the malignant T cells can spread to lymph nodes and internal organs. However...... and lymphatic tumors, originated from the transplanted malignant T cells. In conclusion, we describe a novel mouse model of tumor stage CTCL for future studies of disease dissemination and preclinical evaluations of new therapeutic strategies....

Non-Hodgkin's lymphoma presenting as a primary bladder tumor: a case report

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Molinos-Castro Sonia

2010-04-01

Full Text Available Abstract Introduction Primary lymphoma of the bladder represents 0.2% of all bladder malignancies. Secondary involvement of the bladder by malignant lymphoma occurs in 10% to 50% of cases. Most lymphomas of the bladder are non-Hodgkin's lymphomas of the B-cell type, with preponderance among women. The impact of positron emission tomography (PET on tumor staging has recently become very important due to its use in the study of diagnosis extension and individual therapy design. Case presentation We report the case of a 79-year-old Caucasian man with intermittent haematuria as the presenting symptom of non-Hodgkin's lymphoma of the bladder. He was first diagnosed with primary lymphoma of the bladder using the current staging method, but a positron emission tomography study subsequently revealed that he instead had a secondary involvement of the bladder. Conclusion The staging of non-Hodgkin's lymphomas, which is useful in order to plan accurate therapy, has been changing since the introduction of positron emission tomography scanning. Primary lymphomas of the bladder, although very rare, may be even more uncommon when this imaging technique is used to assess the extension of the disease. Although the interpretation of this technique has some limitations that should be taken into account, the extensive use of positron emission tomography should nonetheless help improve the diagnosis of this disease.

Human adipose tissue-derived mesenchymal stem cells inhibit T-cell lymphoma growth in vitro and in vivo.

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Ahn, Jin-Ok; Chae, Ji-Sang; Coh, Ye-Rin; Jung, Woo-Sung; Lee, Hee-Woo; Shin, Il-Seob; Kang, Sung-Keun; Youn, Hwa-Young

2014-09-01

Human mesenchymal stem cells (hMSCs) are thought to be one of the most reliable stem cell sources for a variety of cell therapies. This study investigated the anti-tumor effect of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) on EL4 murine T-cell lymphoma in vitro and in vivo. The growth-inhibitory effect of hAT-MSCs on EL4 tumor cells was evaluated using a WST-1 cell proliferation assay. Cell-cycle arrest and apoptosis were investigated by flow cytometry and western blot. To evaluate an anti-tumor effect of hAT-MSCs on T-cell lymphoma in vivo, CM-DiI-labeled hAT-MSCs were circumtumorally injected in tumor-bearing nude mice, and tumor size was measured. hAT-MSCs inhibited T-cell lymphoma growth by altering cell-cycle progression and inducing apoptosis in vitro. hAT-MSCs inhibited tumor growth in tumor-bearing nude mice and prolonged survival time. Immunofluorescence analysis showed that hAT-MSCs migrated to tumor sites. hAT-MSCs suppress the growth of T-cell lymphoma, suggesting a therapeutic option for T-cell lymphoma. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

EBV AND HIV-RELATED LYMPHOMA

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Michele Bibas

2009-12-01

Full Text Available HIV-associated lymphoproliferative disorders represent a heterogeneous group of diseases, arising in the presence of HIV-associated immunodeficiency. The overall prevalence of HIV-associated lymphoma is significantly higher compared to that of the general population and it continues to be relevant even after the wide availability of highly active antiretroviral therapy (HAART (1. Moreover, they still represent one of the most frequent cause of death in HIV-infected patients. Epstein–Barr virus (EBV, a γ-Herpesviruses, is involved in human lymphomagenesis, particularly in HIV immunocompromised patients. It has been largely implicated in the development of B-cell lymphoproliferative disorders as Burkitt lymphoma (BL, Hodgkin disease (HD, systemic non Hodgkin lymphoma (NHL, primary central nervous system lymphoma (PCNSL, nasopharyngeal carcinoma (NC. Virus-associated lymphomas are becoming of significant concern for the mortality of long-lived HIV immunocompromised patients, and therefore, research of advanced strategies for AIDS-related lymphomas is an important field in cancer chemotherapy. Detailed understanding of the EBV  lifecycle and related cancers at the molecular level is required for novel strategies of molecular-targeted cancer chemotherapy The linkage of HIV-related lymphoma with EBV infection of the tumor clone has several pathogenetic, prognostic and possibly therapeutic implications which are reviewed herein

SU-E-I-100: Heterogeneity Studying for Primary and Lymphoma Tumors by Using Multi-Scale Image Texture Analysis with PET-CT Images

Energy Technology Data Exchange (ETDEWEB)

Li, Dengwang [Shandong Normal University, Jinan, Shandong Province (China); Wang, Qinfen [Shandong Normal University, Jinan, Shandong (China); Li, H; Chen, J [Shandong Cancer Hospital and Institute, Jinan, Shandong (China)

2014-06-01

Purpose: The purpose of this research is studying tumor heterogeneity of the primary and lymphoma by using multi-scale texture analysis with PET-CT images, where the tumor heterogeneity is expressed by texture features. Methods: Datasets were collected from 12 lung cancer patients, and both of primary and lymphoma tumors were detected with all these patients. All patients underwent whole-body 18F-FDG PET/CT scan before treatment.The regions of interest (ROI) of primary and lymphoma tumor were contoured by experienced clinical doctors. Then the ROI of primary and lymphoma tumor is extracted automatically by using Matlab software. According to the geometry size of contour structure, the images of tumor are decomposed by multi-scale method.Wavelet transform was performed on ROI structures within images by L layers sampling, and then wavelet sub-bands which have the same size of the original image are obtained. The number of sub-bands is 3L+1.The gray level co-occurrence matrix (GLCM) is calculated within different sub-bands, thenenergy, inertia, correlation and gray in-homogeneity were extracted from GLCM.Finally, heterogeneity statistical analysis was studied for primary and lymphoma tumor using the texture features. Results: Energy, inertia, correlation and gray in-homogeneity are calculated with our experiments for heterogeneity statistical analysis.Energy for primary and lymphomatumor is equal with the same patient, while gray in-homogeneity and inertia of primaryare 2.59595±0.00855, 0.6439±0.0007 respectively. Gray in-homogeneity and inertia of lymphoma are 2.60115±0.00635, 0.64435±0.00055 respectively. The experiments showed that the volume of lymphoma is smaller than primary tumor, but thegray in-homogeneity and inertia were higher than primary tumor with the same patient, and the correlation with lymphoma tumors is zero, while the correlation with primary tumor isslightly strong. Conclusion: This studying showed that there were effective heterogeneity

Expression of the c-Met oncogene by tumor cells predicts a favorable outcome in classical Hodgkin's lymphoma.

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Xu, Chuanhui; Plattel, Wouter; van den Berg, Anke; Rüther, Nele; Huang, Xin; Wang, Miao; de Jong, Debora; Vos, Hans; van Imhoff, Gustaaf; Viardot, Andreas; Möller, Peter; Poppema, Sibrand; Diepstra, Arjan; Visser, Lydia

2012-04-01

The c-Met signaling pathway regulates a variety of biological processes, including proliferation, survival and migration. Deregulated c-Met activation has been implicated in the pathogenesis and prognosis of many human malignancies. We studied the function and prognostic significance of c-Met and hepatocyte growth factor protein expression in patients with classical Hodgkin's lymphoma. Expression of c-Met and its ligand, hepatocyte growth factor, were determined by immunohistochemistry. Prognostic values were defined in cohorts of German and Dutch patients with classical Hodgkin's lymphoma. Functional studies were performed on Hodgkin's lymphoma cell lines. Expression of c-Met was detected in the tumor cells of 52% (80/153) of the patients and expression of its ligand, hepatocyte growth factor, in 8% (10/121) of the patients. c-Met expression correlated with a 5-year freedom from tumor progression of 94%, whereas lack of expression correlated with a 5-year freedom from tumor progression of 73% (Pfreedom from tumor progression. In functional studies activation with hepatocyte growth factor did not affect cell growth, while the c-Met inhibitor SU11274 suppressed cell growth by inducing G2/M cell cycle arrest. Although functional studies showed an oncogenic role of the hepatocyte growth factor/c-Met signaling pathway in cell cycle progression, expression of c-Met in tumor cells from patients with classical Hodgkin's lymphoma strongly correlated with a favorable prognosis in two independent cohorts.

Extracellular tumor-related mRNA in plasma of lymphoma patients and survival implications.

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Vanesa Garcia

Full Text Available BACKGROUND: We studied anomalous extracellular mRNAs in plasma from patients with diffuse large B-cell lymphoma (DLBCL and their survival implications. mRNAs studied have been reported in the literature as markers of poor (BCL2, CCND2, MYC and favorable outcome (LMO2, BCL6, FN1 in tumors. These markers were also analyzed in lymphoma tissues to test possible associations with their presence in plasma. METHODOLOGY/PRINCIPAL FINDINGS: mRNA from 42 plasma samples and 12 tumors from patients with DLBCL was analyzed by real-time PCR. Samples post-treatment were studied. The immunohistochemistry of BCL2 and BCL6 was defined. Presence of circulating tumor cells was determined by analyzing the clonality of the immunoglobulin heavy-chain genes by PCR. In DLBCL, MYC mRNA was associated with short overall survival. mRNA targets with unfavorable outcome in tumors were associated with characteristics indicative of poor prognosis, with partial treatment response and with short progression-free survival in patients with complete response. In patients with low IPI score, unfavorable mRNA targets were related to shorter overall survival, partial response, high LDH levels and death. mRNA disappeared in post-treatment samples of patients with complete response, and persisted in those with partial response or death. No associations were found between circulating tumor cells and plasma mRNA. Absence of BCL6 protein in tumors was associated with presence of unfavorable plasma mRNA. CONCLUSIONS/SIGNIFICANCE: Through a non-invasive procedure, tumor-derived mRNAs can be obtained in plasma. mRNA detected in plasma did not proceed from circulating tumor cells. In our study, unfavorable targets in plasma were associated with poor prognosis in B-cell lymphomas, mainly MYC mRNA. Moreover, the unfavorable targets in plasma could help us to classify patients with poor outcome within the good prognosis group according to IPI.

Peripheral T cell lymphoma: Not otherwise specified

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Anusha H Pai

2015-01-01

Full Text Available Peripheral T cell lymphoma (PTCL is a heterogeneous group of hematological tumors originating from mature T cells, which constitutes less than 15% of all non-Hodgkins lymphomas in adults. Primary cutaneous PTCL-not otherwise specified (NOS represent a subgroup of PTCLs with no consistent immunophenotypic, genetic or clinical features. PTCL-NOS frequently has an aggressive course with a tendency for systemic involvement, however, a well-defined therapeutic and prognostic approach has not been outlined yet. We report a case of PTCL-NOS with multiple cutaneous lesions in a young adult male with an emphasis on the treatment modality used.

Axl acts as a tumor suppressor by regulating LIGHT expression in T lymphoma

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Young, Kon-Ji; Park, A-Reum; Choi, Ha-Rim; Lee, Hwa-Youn; Kim, Su-Man; Chung, Byung Yeoup; Park, Chul-Hong; Choi, Hyo Jin; Ko, Young-Hyeh; Bai, Hyoung-Woo; Kang, Hyung-Sik

2017-01-01

Axl is an oncogenic receptor tyrosine kinase that plays a role in many cancers. LIGHT (Lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells) is a ligand that induces robust anti-tumor immunity by enhancing the recruitment and activation of effector immune cells at tumor sites. We observed that mouse EL4 and human Jurkat T lymphoma cells that stably overexpressed Axl also showed high expression of LIGHT. When Jurkat-Axl cells were treated with Gas6, a ligand for Axl, LIGHT expression was upregulated through activation of the PI3K/AKT signaling pathway and transcriptional induction by Sp1. The lytic activity of cytotoxic T lymphocytes and natural killer cells was enhanced by EL4-Axl cells. In addition, tumor volume and growth were markedly reduced due to enhanced apoptotic cell death in EL4-Axl tumor-bearing mice as compared to control mice. We also observed upregulated expression of CCL5 and its receptor, CCR5, and enhanced intratumoral infiltration of cytotoxic T lymphocytes and natural killer cells in EL4-Axl-bearing mice as compared to mock controls. These data strongly suggested that Axl exerts novel tumor suppressor effects by inducing upregulation of LIGHT in the tumor microenvironment of T lymphoma. PMID:28423548

A rare tumoral combination, synchronous lung adenocarcinoma and mantle cell lymphoma of the pleura

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Foroulis Christophoros N

2008-12-01

Full Text Available Abstract Background Coexistence of adenocarcinoma and mantle cell lymphoma in the same or different anatomical sites is extremely rare. We present a case of incidental discovery of primary lung adenocarcinoma and mantle cell lymphoma involving the pleura, during an axillary thoracotomy performed for a benign condition. Case presentation A 73-year old male underwent bullectomy and apical pleurectomy for persistent pneumothorax. A bulla of the lung apex was resected en bloc with a scar-like lesion of the lung, which was located in proximity with the bulla origin, by a wide wedge resection. Histologic examination of the stripped-off parietal pleura and of the bullectomy specimen revealed the synchronous occurrence of two distinct neoplasms, a lymphoma infiltrating the pleura and a primary, early lung adenocarcinoma. Immunohistochemical and fluorescence in situ hybridization assays were performed. The morphologic, immunophenotypic and genetic findings supported the diagnosis of primary lung adenocarcinoma (papillary subtype coexisting with a non-Hodgkin, B-cell lineage, mantle cell lymphoma involving both, visceral and parietal pleura and without mediastinal lymph node involvement. The neoplastic lymphoid cells showed the characteristic immunophenotype of mantle cell lymphoma and the translocation t(11;14. The patient received 6 cycles of chemotherapy, while pulmonary function tests precluded further pulmonary parenchyma resection (lobectomy for his adenocarcinoma. The patient is alive and without clinical and radiological findings of local recurrence or distant relapse from both tumors 14 months later. Conclusion This is the first reported case of a rare tumoral combination involving simultaneously lung and pleura, emphasizing at the incidental discovery of the two coexisting neoplasms during a procedure performed for a benign condition. Any tissue specimen resected during operations performed for non-tumoral conditions should be routinely sent for

Vorinostat in Treating Patients With Metastatic or Unresectable Solid Tumors or Lymphoma and Liver Dysfunction

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2014-02-21

IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Stage IV Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Waldenström Macroglobulinemia

Th1/2 Immune Response Signature Predicts Outcome after Dose-Dense Immunochemotherapy in Patients with High Risk Diffuse Large B-Cell Lymphoma – Results from Nordic Lymphoma Group Trials

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M, Autio; Jørgensen, Judit Meszaros; SK, Leivonen

treatment-specific roles in diffuse large B-cell lymphoma. For the high risk DLBCL patients treated with dose-dense immunochemotherapy, high expression of type 1/2 immune response signature genes predicts a poor outcome. A detailed characterization of immune cell composition in the tumor microenvironment......Introduction: Despite better therapeutic options and improved survival of diffuse large B-cell lymphoma (DLBCL), 30-40% of the patients still relapse and have dismal prognosis. Recently, the impact of genomic aberrations, allowing lymphoma cells to escape immune recognition on DLBCL pathogenesis...... has been recognized. However, whether immune related signatures could be used as determinants for treatment outcome has not been rigorously evaluated. Here, our aim was to elucidate the immunologic characteristics of the tumor microenvironment, and associate the findings with outcome in patients...

CARDIAC LYMPHOMA IN DOG

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G. D. Cruz

2016-11-01

Full Text Available Lymphoma is a lymphoid tumor that originates in hematopoietic organs such as lymph node, spleen or liver. In dogs, the overall prevalence of cardiac tumors was estimated to be only 0.19% based on the results of the survey of a large database, and lymphomas accounts for approximately 2% of all cardiac tumors. In general, the involvement of the myocardium is rarely described in canine lymphoma. Currently, there is no evidence of a viral association with primary cardiac lymphoma in dogs, but other types of immunosuppression may contribute to abnormal events, such as involvement primary cardiac. The aim of this study was to analyze a case of sudden death of a bitch, SRD, aged 10, who had the final diagnosis of cardiac lymphoma.

Predictive value of PET response combined with baseline metabolic tumor volume in peripheral T-cell lymphoma patients

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Cottereau, Anne-Segolene; El-Galaly, Tarec C; Becker, Stéphanie

2018-01-01

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive non-Hodgkin lymphomas with poor outcomes with current therapy. We investigated if response assessed with Positron Emission Tomography/computed tomography (PET/CT) combined with baseline total metabolic tumor volume (TMTV) co...

Targeted therapy for Hodgkin lymphoma and systemic anaplastic large cell lymphoma: focus on brentuximab vedotin

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Chen X

2013-12-01

Full Text Available Xueyan Chen, Lorinda A Soma, Jonathan R FrommDepartment of Laboratory Medicine, University of Washington Medical Center, Seattle, WA, USAAbstract: Despite the relative success of chemotherapy for Hodgkin lymphoma (HL and systemic anaplastic large cell lymphoma (ALCL, novel therapeutic agents are needed for refractory or relapsed patients. Targeted immunotherapy has emerged as a novel treatment option for these patients. Although unconjugated anti-cluster of differentiation (CD30 antibodies showed minimal antitumor activity in early clinical trials, development of antibody–drug conjugates (ADCs appears promising. Brentuximab vedotin is an ADC composed of an anti-CD30 antibody linked to a potent microtubule-disrupting agent monomethyl auristatin E (MMAE. It has the ability to target CD30-positive tumor cells and, once bound to CD30, brentuximab vedotin is internalized and MMAE is released to induce cell cycle arrest and apoptosis. In two phase II trials, objective response was reported in 75% and 86% of patients with refractory or relapsed HL and systemic ALCL, respectively, with an acceptable toxicity profile. Based on these studies, the US Food and Drug Administration (FDA granted accelerated approval of brentuximab vedotin in August 2011 for the treatment of refractory and relapsed HL and ALCL. We review the key characteristics of brentuximab vedotin, clinical data supporting its therapeutic efficacy, and current ongoing trials to explore its utility in other CD30-positive malignancies.Keywords: classical Hodgkin lymphoma, systemic anaplastic large cell lymphoma, CD30, brentuximab vedotin, SGN-35

Autologous stem-cell transplantation in Hodgkin’s lymphoma: analysis of a therapeutic option

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Adriano de Moraes Arantes

2011-06-01

Full Text Available Objective: To report the clinical progress of patients with Hodgkin’slymphoma treated with autologous transplantation after failure orrelapse of first-line treatment with chemotherapy and/or radiationtherapy. Methods: The results of a retrospective analysis of 31patients submitted to autologous transplantation as second-linetreatment, between April 2000 and December 2008, were analyzed.Fourteen men and seventeen women, with a median age of 27 years,were submitted to autologous transplantation for relapsed (n = 21or refractory (n = 10 Hodgkin’s lymphoma. Results: Mortalityrelated to treatment in the first 100 days after transplant was 3.2%.With a mean follow-up period of 18 months (range: 1 to 88 months,the probability of global survival and progression-free survival in18 months was 84 and 80%, respectively. The probability of globalsurvival and progression-free survival at 18 months for patients withchemosensitive relapses (n = 21 was 95 and 90%, respectively,versus 60 and 45% for patients with relapses resistant to chemotherapy(n = 10 (p = 0.001 for global survival; p = 0.003 for progressionfreesurvival. In the multivariate analysis, absence of disease or pretransplant disease < 5 cm were favorable factors for global survival (p= 0.02; RR: 0.072; 95%CI: 0.01-0.85 and progression-free survival (p= 0.01; RR: 0.040; 95%CI: 0.007-0.78. Conclusion: Autologous transplantation of stem-cells is a therapeutic option for Hodgkin’s lymphoma patients after the first relapse. Promising results were observed in patients with a low tumor burden at transplant.

Potential benefits of therapeutic splenectomy for patients with Hodgkin's disease and non-Hodgkin's lymphomas

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Schreiber, D.P.; Jacobs, C.; Rosenberg, S.A.; Cox, R.S.; Hoppe, R.T.

1985-01-01

Thirty-four patients with Hodgkin's disease and non-Hodgkin's lymphoma underwent therapeutic splenectomies to improve hematologic tolerance for chemotherapy. The mean age was 40 years; there were 16 males and 18 females. Fourteen had Hodgkin's disease, 19 had non-Hodgkin's lymphoma, and 1 had malignant histocytosis. Nineteen had palpable splenomegaly, 19 had marrow involvement and 20 had splenic involvement by lymphoma. The following data were analyzed before and after splenectomy: mean white blood cell count (WBC) and platelet count on planned first day of cycle, delay ratio of chemotherapy delivery and percent maximal dose rate. Thirteen patients had non-Hodgkin's lymphoma, splenomegaly and positive bone marrow and showed significant benefit in all of the aforementioned parameters. Of the patients with prior irradiation, only those who completed their radiation greater than six months prior to splenectomy showed benefit. Ten patients had Hodgkin's disease, negative bone marrow and no splenomegaly. This group showed significant improvement in mean platelet count but more limited benefit in delay ratio and percent maximal dose rate. Thus, selected patients with lymphoma who are experiencing delays in chemotherapy because of poor count tolerance may benefit from splenectomy

Importance of radioimmunoassay for the determination of tumor markers in the diagnosis of malignant lymphomas

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Purizhanskij, I.I.; Pavlichuk, S.N.; Toritsina, L.K.

1989-01-01

The investigation was conducted to study the role of the determination of tumor markers (CEA, β 2 -microglobulin, IgE and ferritin) in patients with malignant lymphomas. Altogether 66 patients with Hodgkin's disease, 60 with non-Hodgkin's lymphomas and 15 with clinocohematological remission over one year were investigated, using radioimmunoassay with commercial kits of reagents. An increase in the level of β 2 -MG was shown to depend on the spreading of a lymphoproliferative process. An elevated level of IgE was noted in Hodgkin's disease whereas a significant rise was unnoticed in non-Hodgkin's lymphomas. An increase in the level of serum ferritin was noted in an advanced and aggressive lymphoproliferative process. The CEA test in malignant lymphomas is not informative

Farnesyl transferase inhibitors induce extended remissions in transgenic mice with mature B cell lymphomas

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Refaeli Yosef

2008-05-01

Full Text Available Abstract Background We have used a mouse model based on overexpression of c-Myc in B cells genetically engineered to be self-reactive to test the hypothesis that farnesyl transferase inhibitors (FTIs can effectively treat mature B cell lymphomas. FTIs are undergoing clinical trials to treat both lymphoid and non-lymphoid malignancies and we wished to obtain evidence to support the inclusion of B cell lymphomas in future trials. Results We report that two FTIs, L-744,832 and SCH66336, blocked the growth of mature B cell lymphoma cells in vitro and in vivo. The FTI treatment affected the proliferation and survival of the transformed B cells to a greater extent than naïve B cells stimulated with antigen. In syngeneic mice transplanted with the transgenic lymphoma cells, L-744,832 treatment prevented the growth of the tumor cells and the morbidity associated with the resulting lymphoma progression. Tumors that arose from transplantation of the lymphoma cells regressed with as little as three days of treatment with L-744,832 or SCH66336. Treatment of these established lymphomas with L-744,832 for seven days led to long-term remission of the disease in approximately 25% of animals. Conclusion FTI treatment can block the proliferation and survival of self-reactive transformed B cells that overexpress Myc. In mice transplanted with mature B cell lymphomas, we found that FTI treatment led to regression of disease. FTIs warrant further consideration as therapeutic agents for mature B cell lymphomas and other lymphoid tumors.

HSP90 inhibitor 17-AAG selectively eradicates lymphoma stem cells.

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Newman, Bryan; Liu, Yan; Lee, Hsiu-Fang; Sun, Duxin; Wang, Yin

2012-09-01

Cancer stem cells (CSC; also called tumor-initiating cells) comprise tumor cell subpopulations that preserve the properties of quiescence, self-renewal, and differentiation of normal stem cells. In addition, CSCs are therapeutically important because of their key contributions toward drug resistance. The hypoxia-inducible transcription factor HIF1α is critical for CSC maintenance in mouse lymphoma. In this study, we showed that low concentrations of the HSP90 inhibitor 17-AAG eliminate lymphoma CSCs in vitro and in vivo by disrupting the transcriptional function of HIF1α, a client protein of HSP90. 17-AAG preferentially induced apoptosis and eliminated the colony formation capacity of mouse lymphoma CSCs and human acute myeloid leukemia (AML) CSCs. However, low concentrations of 17-AAG failed to eliminate highly proliferative lymphoma and AML cells (non-CSCs), in which the AKT-GSK3 signaling pathway is constitutively active. The heat shock transcription factor HSF1 is highly expressed in non-CSCs, but it was weakly expressed in lymphoma CSCs. However, siRNA-mediated attenuation of HSF1 abrogated the colony formation ability of both lymphoma and AML CSCs. This study supports the use of 17-AAG as a CSC targeting agent and, in addition, shows that HSF1 is an important target for elimination of both CSCs and non-CSCs in cancer. ©2012 AACR.

Risk of Lymphoma in Patients With Inflammatory Bowel Disease Treated With Anti-Tumor Necrosis Factor Alpha Agents: A Systematic Review and Meta-analysis.

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Yang, Chen; Huang, Junlin; Huang, Xiaowen; Huang, Shaozhuo; Cheng, Jiaxin; Liao, Weixin; Chen, Xuewen; Wang, Xueyi; Dai, Shixue

2018-05-12

The association between anti-tumor necrosis factor alpha agents and the risk of lymphoma in patients with inflammatory bowel disease has already been sufficiently reported. However, the results of these studies are inconsistent. Hence, this analysis was conducted to investigate whether anti-tumor necrosis factor alpha agents can increase the risk of lymphoma in inflammatory bowel disease patients. MEDLINE, EMBASE and the Cochrane Library were searched to identify relevant studies which evaluated the risk of lymphoma in inflammatory bowel disease patients treated with anti-tumor necrosis factor alpha agents. A random-effects meta-analysis was performed to calculate the pooled incidence rate ratios as well as risk ratios. Twelve studies comprising 285811 participants were included. The result showed that there was no significantly increased risk of lymphoma between anti-tumor necrosis factor alpha agents exposed and anti-tumor necrosis factor alpha agents unexposed groups (random effects: incidence rate ratio [IRR], 1.43 95%CI, 0.91-2.25, p= 0.116; random effects: risk ratio [RR], 0.83 95%CI, 0.47-1.48, p=0.534). However, monotherapy of anti-tumor necrosis factor alpha agents (random effects: IRR=1.65, 95%CI, 1.16-2.35; p=0.006; random effects: RR=1.00, 95%CI, 0.39-2.59; p=0.996) or combination therapy (random effects: IRR=3.36, 95%CI, 2.23-5.05; ptumor necrosis factor alpha agents in patients with inflammatory bowel disease is not associated with a higher risk of lymphoma. Combination therapy and anti-tumor necrosis factor alpha agents monotherapy can significantly increase the risk of lymphoma in patients with inflammatory bowel disease.

Translation initiation complex eIF4F is a therapeutic target for dual mTOR kinase inhibitors in non-Hodgkin lymphoma

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Stenson, Mary J.; Maurer, Matthew J.; Wellik, Linda E.; Link, Brian; Hege, Kristen; Dogan, Ahmet; Sotomayor, Eduardo; Witzig, Thomas; Gupta, Mamta

2015-01-01

Deregulated mRNA translation has been implicated in disease development and in part is controlled by a eukaryotic initiation complex eIF4F (composed of eIF4E, eIF4G and eIF4A). We demonstrate here that the cap bound fraction from lymphoma cells was enriched with eIF4G and eIF4E indicating that lymphoma cells exist in an activated translational state. Moreover, 77% (110/142) of diffuse large B cell lymphoma tumors expressed eIF4E and this was associated with an inferior event free survival. Over-expression of wild-type eIF4E (eIF4EWT) but not cap-mutant eIF4E (eIF4Ecap mutant) increased the activation of the eIF4F complex. Treatment with the active-site dual mTOR inhibitor CC214-1 reduced the level of the eIF4F complex by decreasing the cap bound fraction of eIF4G and increasing the levels of 4E-BP1. CC214-1 inhibited both the cap dependent and global protein translation. CC214-1 inhibited c-Myc, and cyclin D3 translation by decreasing polysomal fractions from lymphoma cells. Inhibition of eIF4E with shRNA further decreased the CC214-1 induced inhibition of the eIF4F complex, c-Myc, cyclin D3 translation, and colony formation. These studies demonstrate that the eIF4F complex is deregulated in aggressive lymphoma and that dual mTOR therapy has therapeutic potential in these patients. PMID:25839159

Ovarian lymphoma

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Bonet Fonseca, Ivan; Diaz Anaya, Amnia; Francis, Tabu

2012-01-01

50 % of pediatric oncologic pathology corresponds to mass or solid tumors, reaching about 20 % of total abdomen. The tumors that most frequently occur in the abdomen are nephroblastoma or Wilms tumor, Burkitts lymphoma, neuroblastoma, and ovarian germ cell tumors

Quantitative PCR for HTLV-1 provirus in adult T-cell leukemia/lymphoma using paraffin tumor sections.

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Kato, Junki; Masaki, Ayako; Fujii, Keiichiro; Takino, Hisashi; Murase, Takayuki; Yonekura, Kentaro; Utsunomiya, Atae; Ishida, Takashi; Iida, Shinsuke; Inagaki, Hiroshi

2016-11-01

Detection of HTLV-1 provirus using paraffin tumor sections may assist the diagnosis of adult T-cell leukemia/lymphoma (ATLL). For the detection, non-quantitative PCR assay has been reported, but its usefulness and limitations remain unclear. To our knowledge, quantitative PCR assay using paraffin tumor sections has not been reported. Using paraffin sections from ATLLs and non-ATLL T-cell lymphomas, we first performed non-quantitative PCR for HTLV-1 provirus. Next, we determined tumor ratios and carried out quantitative PCR to obtain provirus copy numbers. The results were analyzed with a simple regression model and a novel criterion, cut-off using 95 % rejection limits. Our quantitative PCR assay showed an excellent association between tumor ratios and the copy numbers (r = 0.89, P paraffin tumor sections may be useful for the screening of ATLL cases, especially in HTLV-1 non-endemic areas where easy access to serological testing for HTLV-1 infection is limited. © 2016 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

Rapid progression of mediastinal tumor within a few days: A case report of T cell lymphoblastic lymphoma

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Ahn, Tae Ran; Lee, Young Kyung; Jun, Hyun Jung; Jung, Eun Ah; Son, Jin Sung [Seoul Medical Center, Seoul (Korea, Republic of)

2016-05-15

T-cell lymphoblastic lymphoma is a highly aggressive tumor derived from lymphocyte of the thymus, which accounts for 2% of non-Hodgkin's lymphoma. The disease occurs most commonly in adolescent and young adult males. It often results in respiratory emergency because of high proliferation rate. In this case, we confirmed the rapid progression of T-cell lymphoblastic lymphoma through the chest CT scan with one week interval. Three days of empirical chemotherapy resulted in substantial reduction of mediastinal mass, pleural thickening and pleural effusion.

Adult T-cell leukemia/lymphoma treatment in Bahia, Brazil

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Pedro Dantas Oliveira

Full Text Available Abstract Background: Adult T-cell leukemia/lymphoma is a peripheral disease associated with human T-cell lymphotropic virus type 1. Treatment is carried out according to clinical type with watchful waiting being recommended for less aggressive types. Aggressive adult T-cell leukemia/lymphoma is generally treated with chemotherapy and/or antivirals. The objective of this study was to correlate the survival of patients diagnosed in Bahia, Brazil, with the therapeutic approaches employed and to evaluate what issues existed in their treatment processes. Methods: Eighty-three adult T-cell leukemia/lymphoma patients (26 smoldering, 23 chronic, 16 acute, 13 lymphoma and five primary cutaneous tumoral with available data were included in this study. Results: Complete response was achieved in seven smoldering patients with symptomatic treatment, in two with chronic disease using antivirals/chemotherapy, in one with acute disease using antivirals and in one lymphoma using the LSG15 regimen [vincristine, cyclophosphamide, doxorubicin, and prednisolone (VCAP; doxorubicin, ranimustine, and prednisolone (AMP; and vindesine, etoposide, carboplatin, and prednisolone (VECP]. Smoldering patients who received symptomatic treatment presented longer survival. Favorable chronic patients treated with antivirals presented longer survival compared to the unfavorable subtype. However, for the acute form, first-line chemotherapy was better, albeit without significance, than antivirals. Only one of the patients with lymphoma and primary cutaneous tumors responded. Conclusions: Watchful waiting associated with phototherapy represents the best option for smoldering adult T-cell leukemia/lymphoma with survival in Bahia being superior to that described in Japan. There was a trend of better results with zidovudine/interferon-alpha in favorable chronic disease. Excellent results were achieved in the lymphoma type treated with the LSG15 protocol. Patients are diagnosed late

Horizontal transmission of malignancy: in-vivo fusion of human lymphomas with hamster stroma produces tumors retaining human genes and lymphoid pathology.

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David M Goldenberg

Full Text Available We report the in-vivo fusion of two Hodgkin lymphomas with golden hamster cheek pouch cells, resulting in serially-transplanted (over 5-6 years GW-532 and GW-584 heterosynkaryon tumor cells displaying both human and hamster DNA (by FISH, lymphoma-like morphology, aggressive metastasis, and retention of 7 human genes (CD74, CXCR4, CD19, CD20, CD71, CD79b, and VIM out of 24 tested by PCR. The prevalence of B-cell restricted genes (CD19, CD20, and CD79b suggests that this uniform population may be the clonal initiating (malignant cells of Hodgkin lymphoma, despite their not showing translation to their respective proteins by immunohistochemical analysis. This is believed to be the first report of in-vivo cell-cell fusion of human lymphoma and rodent host cells, and may be a method to disclose genes regulating both organoid and metastasis signatures, suggesting that the horizontal transfer of tumor DNA to adjacent stromal cells may be implicated in tumor heterogeneity and progression. The B-cell gene signature of the hybrid xenografts suggests that Hodgkin lymphoma, or its initiating cells, is a B-cell malignancy.

Reduction of Myeloid-derived Suppressor Cells and Lymphoma Growth by a Natural Triterpenoid

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Radwan, Faisal F. Y.; Hossain, Azim; God, Jason M.; Leaphart, Nathan; Elvington, Michelle; Nagarkatti, Mitzi; Tomlinson, Stephen; Haque, Azizul

2016-01-01

Lymphoma is a potentially life threatening disease. The goal of this study was to investigate the therapeutic potential of a natural triterpenoid, Ganoderic acid A (GA-A) in controlling lymphoma growth both in vitro and in vivo. Here, we show that GA-A treatment induces caspase-dependent apoptotic cell death characterized by a dose-dependent increase in active caspases 9 and 3, up-regulation of pro-apoptotic BIM and BAX proteins, and a subsequent loss of mitochondrial membrane potential with release of cytochrome c. In addition to GA-A’s anti-growth activity, we show that lower doses of GA-A enhance HLA class II-mediated antigen presentation and CD4+ T cell recognition of lymphoma in vitro. The therapeutic relevance of GA-A treatment was also tested in vivo using the EL4 syngeneic mouse model of metastatic lymphoma. GA-A-treatment significantly prolonged survival of EL4 challenged mice and decreased tumor metastasis to the liver, an outcome accompanied by a marked down-regulation of STAT3 phosphorylation, reduction myeloid-derived suppressor cells (MDSCs), and enhancement of cytotoxic CD8+ T cells in the host. Thus, GA-A not only selectively induces apoptosis in lymphoma cells, but also enhances cell-mediated immune responses by attenuating MDSCs, and elevating Ag presentation and T cell recognition. The demonstrated therapeutic benefit indicates that GA-A is a candidate for future drug design for the treatment of lymphoma. PMID:25142864

Reduction of myeloid-derived suppressor cells and lymphoma growth by a natural triterpenoid.

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Radwan, Faisal F Y; Hossain, Azim; God, Jason M; Leaphart, Nathan; Elvington, Michelle; Nagarkatti, Mitzi; Tomlinson, Stephen; Haque, Azizul

2015-01-01

Lymphoma is a potentially life threatening disease. The goal of this study was to investigate the therapeutic potential of a natural triterpenoid, Ganoderic acid A (GA-A) in controlling lymphoma growth both in vitro and in vivo. Here, we show that GA-A treatment induces caspase-dependent apoptotic cell death characterized by a dose-dependent increase in active caspases 9 and 3, up-regulation of pro-apoptotic BIM and BAX proteins, and a subsequent loss of mitochondrial membrane potential with release of cytochrome c. In addition to GA-A's anti-growth activity, we show that lower doses of GA-A enhance HLA class II-mediated antigen (Ag) presentation and CD4+ T cell recognition of lymphoma cells in vitro. The therapeutic relevance of GA-A treatment was also tested in vivo using the EL4 syngeneic mouse model of metastatic lymphoma. GA-A-treatment significantly prolonged survival of EL4 challenged mice and decreased tumor metastasis to the liver, an outcome accompanied by a marked down-regulation of STAT3 phosphorylation, reduction myeloid-derived suppressor cells (MDSCs), and enhancement of cytotoxic CD8+ T cells in the host. Thus, GA-A not only selectively induces apoptosis in lymphoma cells, but also enhances cell-mediated immune responses by attenuating MDSCs, and elevating Ag presentation and T cell recognition. The demonstrated therapeutic benefit indicates that GA-A is a candidate for future drug design for the treatment of lymphoma. © 2014 Wiley Periodicals, Inc.

Transmission of naturally occurring lymphoma in macaque monkeys.

OpenAIRE

Hunt, R D; Blake, B J; Chalifoux, L V; Sehgal, P K; King, N W; Letvin, N L

1983-01-01

Spontaneously occurring rhesus monkey lymphomas were transmitted into healthy rhesus monkeys by using tumor cell suspensions. The naturally arising tumors included an immunoblastic sarcoma and an undifferentiated lymphoma. Recipient animals developed undifferentiated lymphomas, poorly differentiated lymphomas, or parenchymal lymphoproliferative abnormalities suggestive of early lesions of lymphoma. Some of these animals developed such opportunistic infections as cytomegalovirus hepatitis and ...

DNA double-strand break rejoining in human follicular lymphoma and glioblastoma tumor cells

NARCIS (Netherlands)

Macann, AMJ; Britten, RA; Poppema, S; Pearcey, R; Rosenberg, E; Allalunis-Turner, MJ; Murray, D

2000-01-01

Follicle center cell lymphoma is among the most radioresponsive of human cancers. To assess whether this radioresponsiveness might be a result of a compromised ability of the tumor cells to accomplish the biologically-effective repair of DNA double-strand breaks (DSBs), we have measured i) the

Preliminary results of MR imaging of lymphoma: Distinguishing active tumor from benign residue

International Nuclear Information System (INIS)

Drace, J.; Baker, L.L.; Chang, P.; Castellino, R.A.

1987-01-01

Distinguishing tumor from benign posttreatment tissue based on both morphologic and tissue characteristics is critically important. Patients are studied before, during, and after treatment; at the time of recurrence; and on long-term follow-up. Multisection spin-echo sequences in orthogonal planes and a special single-section tissue characterization matrix of 16 different repetition time/echo time combinations are used. These basic images are used for cluster analysis (approximate fuzzy C means), T1-T2 synthetic images, linear combinations, and comparison with internal standards. Preliminary results in 35 patients imaged before treatment and 12 patients with follow-up examinations consistently show lymphoma masses to have complex architecture with high T2-weighted signal and moderate T1-weighted signal, distinct from posttreatment fibrosis. Uncommon components of active tumor with low T2-weighted signal appear distinct from fibrosis on T1-weighted images. Preliminary cluster analysis results show distinct clustering of active lymphoma versus fibrosis and biopsy-proved cystic degeneration

Pattern of malignant solid tumors and lymphomas in children in the east delta of Egypt: A five-year study.

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Hesham, Mervat; Atfy, Mervat; Hassan, Tamer; Abdo, Mohamed; Morsy, Saed; El Malky, Mohamed; Latif, Dalia Abdel

2014-11-01

Worldwide, the incidence and mortality rates of childhood cancers differ. The study of incidence patterns and survival rates in childhood malignancies is important in aiding in the planning of treatment centers and in obtaining further information with regard to the etiology. Few studies have investigated the survival in cases of childhood solid tumors in Egypt. The aim of the current study was to evaluate the patterns, frequency and outcome of solid tumors and lymphomas in children admitted to and followed up at the Pediatric Oncology Department of Zagazig University Hospital (Zagazig, Egypt) over a duration of 5 years (January 2004 to December 2008). A retrospective study was conducted, which included 155 children with solid tumors and lymphomas. The medical records were reviewed and the relevant data collected, in particular, those concerning demographic, clinical, histopathological, laboratory and imaging data as well as the treatment plans and outcomes. The mean age of patients was 5.6±3.04 years at diagnosis. The patients comprised 94 males and 61 females. Non-Hodgkin lymphoma (NHL) was the most common tumor type, followed by neuroblastoma (31.0 and 29.0%, respectively). When patients were stratified in terms of age (<5, ≥5 but <10, and ≥10 years), the <5-years-of-age group exhibited the greatest number of patients. Fever, pallor and pain were the most frequent initial clinical presentations among the patients and stage II was the most common stage (39.1%) followed by stage IV, III and I (35.0, 20.3 and 5.6% respectively). The overall 5-year survival rate in the study group was 66.7%. The survival rate was significantly higher in patients with Wilm's tumor and Hodgkin lymphoma, followed by NHL (92.0, 88.0 and 72.0%, respectively; P<0.001), while the mortality rate was significantly higher in patients with neuroblastoma (P<0.001). In conclusion, NHL and neuroblastoma were the most common tumors; the survival rates were higher in patients with Wilm's tumor

Diagnostic imaging of lymphomas in pediatric patients

International Nuclear Information System (INIS)

Petrova, A.

2010-01-01

Lymphoma is the third most common malignancy in children, after leukemias and brain tumors, most commonly during early childhood before 14 years. In definite stages cancer can engage all organs and systems. These conditions associate with immunodeficiency, increased susceptibility to infections and second neoplasms. The social importance of the problem requires early diagnosis, accurate staging, and assessment of the treatment and determination of the risk for relapse of the disease. The aim of the present review is to represent the role of the modern methods of diagnostic imaging - ultrasonography (US), Computed Tomography (CT), Magnetic Resonance Imaging (MRI) and Positron Emisson Tomography (PET) scan in the process of diagnostics, in the decision of therapeutic strategy and the follow-up of children with lymphomas

Co-targeting of Tiam1/Rac1 and Notch ameliorates chemoresistance against doxorubicin in a biomimetic 3D lymphoma model

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Ikram, Muhammad; Lim, Yeseon; Baek, Sun-Yong; Jin, Songwan; Jeong, Young Hun; Kwak, Jong-Young; Yoon, Sik

2018-01-01

Lymphoma is a heterogeneous disease with a highly variable clinical course and prognosis. Improving the prognosis for patients with relapsed and treatment-resistant lymphoma remains challenging. Current in vitro drug testing models based on 2D cell culture lack natural tissue-like structural organization and result in disappointing clinical outcomes. The development of efficient drug testing models using 3D cell culture that more accurately reflects in vivo behaviors is vital. Our aim was to establish an in vitro 3D lymphoma model that can imitate the in vivo 3D lymphoma microenvironment. Using this model, we explored strategies to enhance chemosensitivity to doxorubicin, an important chemotherapeutic drug widely used for the treatment of hematological malignancies. Lymphoma cells grown in this model exhibited excellent biomimetic properties compared to conventional 2D culture including (1) enhanced chemotherapy resistance, (2) suppressed rate of apoptosis, (3) upregulated expression of drug resistance genes (MDR1, MRP1, BCRP and HIF-1α), (4) elevated levels of tumor aggressiveness factors including Notch (Notch-1, -2, -3, and -4) and its downstream molecules (Hes-1 and Hey-1), VEGF and MMPs (MMP-2 and MMP-9), and (5) enrichment of a lymphoma stem cell population. Tiam1, a potential biomarker of tumor progression, metastasis, and chemoresistance, was activated in our 3D lymphoma model. Remarkably, we identified two synergistic therapeutic oncotargets, Tiam1 and Notch, as a strategy to combat resistance against doxorubicin in EL4 T and A20 B lymphoma. Therefore, our data suggest that our 3D lymphoma model is a promising in vitro research platform for studying lymphoma biology and therapeutic approaches. PMID:29416753

Identification of Candidate B-Lymphoma Genes by Cross-Species Gene Expression Profiling

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Tompkins, Van S.; Han, Seong-Su; Olivier, Alicia; Syrbu, Sergei; Bair, Thomas; Button, Anna; Jacobus, Laura; Wang, Zebin; Lifton, Samuel; Raychaudhuri, Pradip; Morse, Herbert C.; Weiner, George; Link, Brian; Smith, Brian J.; Janz, Siegfried

2013-01-01

Comparative genome-wide expression profiling of malignant tumor counterparts across the human-mouse species barrier has a successful track record as a gene discovery tool in liver, breast, lung, prostate and other cancers, but has been largely neglected in studies on neoplasms of mature B-lymphocytes such as diffuse large B cell lymphoma (DLBCL) and Burkitt lymphoma (BL). We used global gene expression profiles of DLBCL-like tumors that arose spontaneously in Myc-transgenic C57BL/6 mice as a phylogenetically conserved filter for analyzing the human DLBCL transcriptome. The human and mouse lymphomas were found to have 60 concordantly deregulated genes in common, including 8 genes that Cox hazard regression analysis associated with overall survival in a published landmark dataset of DLBCL. Genetic network analysis of the 60 genes followed by biological validation studies indicate FOXM1 as a candidate DLBCL and BL gene, supporting a number of studies contending that FOXM1 is a therapeutic target in mature B cell tumors. Our findings demonstrate the value of the “mouse filter” for genomic studies of human B-lineage neoplasms for which a vast knowledge base already exists. PMID:24130802

Study on biodistribution and imaging of radioiodinated antisense oligonucleotides in nude mice bearing human lymphoma

International Nuclear Information System (INIS)

Wang, R.F.; Shen, J.; Zhang, C.L.; Liu, M.; Guo, F.Q.

2005-01-01

The incidence of sporadic lymphoma has risen due to an increase in immunosuppressed patients, particularly those with human immunodeficiency virus (HIV) infection. Sometimes suspect lymphoma has an undetectable location and we can not get the pathological specimen. Management of lymphoma is also difficult because the persistence of a significant number of residual tumor cells after intensive treatment. These relative failures can be attributed to make us choose this study for opening a new diagnostic and therapeutic field of lymphoma from molecular level. Immunoglobulin (Ig) heavy chain framework region (FR) of V1 family have been verified to be a major determinant of malignant phenotype of V1 family B-cell lymphoma. Most of targets for tumor antisense therapy study are protooncogenes, such as c-myc, bc1-2, which are broad -spectrum tumor imaging agents. The aim of this study was to investigate the possibility of using radioiodine labeled FR antisense oligonucleotides (ASONs) as an imaging agent or antisense therapeutic radiopharmaceutical in lymphoma. A 18-mer partial phosphorothioate oligonucleotide sequence was synthesized and grafted in 5 ' with a tyramine group which was further labeled with 125 I or 131 I using the chloramine T method. Normal CD-1 mice were injected via a tail vein with 148 kBq of 125 I-FR-ASON (2∼3 μ g). Animals were sacrificed at 1, 2, 4 and 24 h and tissue samples were studied. Liposome-mediated 3.33 MBq of 131 I-FR-ASON (7 ∼ 9μ g) was injected intratumorally into tumor-bearing BALB/c mice (6 weeks after inoculation of 10 7 Namalwa cells) meanwhile liposome-mediated 131 I labeled sense oligonucleotides served as controls. Biodistribution was monitored by sequential scintigraphy and organ radioactivity measurement 24 h after injection. The percentage of the injected dose per gram (%ID/g) of tumor and tumor/ non-tumor tissue ratios (T/NT) were calculated for each group of mice and the difference between two groups was assessed. The 5

CK1δ in lymphoma: gene expression and mutation analyses and validation of CK1δ kinase activity for therapeutic application

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Brigitte Sophia Winkler

2015-02-01

Full Text Available The prognosis of lymphoid neoplasms has improved considerably during the last decades. However, treatment response for some lymphoid neoplasms is still poor, indicating the need for new therapeutic approaches. One promising new strategy is the inhibition of kinases regulating key signal transduction pathways, which are of central importance in tumorigenesis. Kinases of the CK1 family may represent an attractive drug target since CK1 expression and/or activity are associated with the pathogenesis of malignant diseases. Over the last years efforts were taken to develop highly potent and selective CK1-specific inhibitor compounds and their therapeutic potential has now to be proved in pre-clinical trials. Therefore, we analyzed expression and mutational status of CK1δ in several cell lines representing established lymphoma entities, and also measured the mRNA expression level in primary lymphoma tissue as well as non-neoplastic blood cells. For a selection of lymphoma cell lines we furthermore determined CK1δ kinase activity and demonstrated therapeutic potential of CK1-specific inhibitors as a putative therapeutic option in the treatment of lymphoid neoplasms.

Doxorubicin plus tumor necrosis factor alpha combination treatments in EL4-lymphoma-bearing C57BL/6 mice.

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Ehrke, M J; Verstovsek, S; Ujházy, P; Meer, J M; Eppolito, C; Maccubbin, D L; Mihich, E

1998-02-01

The therapeutic efficacy of a total of 42 single-agent or combination protocols involving doxorubicin (Adriamycin, ADM) and tumor necrosis factor alpha (TNFalpha) were evaluated in the syngeneic murine lymphoma model, C57BL/6-EL4. Combination treatments were the most effective and the therapeutic effects were schedule-dependent; e.g. it was generally advantageous for ADM to precede TNFalpha administration. Two protocols selected for further study were 4 mg/kg ADM i.v. on days 1 and 8 plus TNFalpha, i.v., at either 16000 U (7 microg)/injection, on days 1 and 8 or 4000 U (1.7 microg)/injection, on days 11-15. Survival of mice bearing one of four EL4 sublines having different in vitro drug sensitivities was assessed. These sublines were E10 (ADM-sensitive/TNFalpha-resistant), E16 (sensitive/sensitive), ER2 (ADM-resistant/TNFalpha-sensitive) and ER13 (resistant/resistant). Between 80% and 100% long-term survivors (i.e. tumor free on day 60) were obtained with the two treatments in mice bearing ADM-sensitive sublines, even though one of these sublines, E10, was resistant to TNFalpha in vitro. Induction of long-term survival appeared, therefore, to correlate with in vitro defined sensitivity/resistance to ADM, but not to TNFalpha Treatment-induced modulations of tumoricidal immune effector functions were also examined. Taken together, the results indicated that induction of long-term survival involved complex interactions of: (1) ADM-induced tumor modifications, including, but not limited to, tumor debulking, (2) combination-treatment-induced modifications of splenic cytolytic T cell and macrophage activities, and (3) the restoration of thymus cellularity. Finally, when long-term survivors resulting from treatment of E10- or E16-bearing mice were implanted with ER2 on day 120, the majority survived, indicating that long-term immune memory, capable of recognizing drug resistant variants, had been established.

Molecular resemblance of an AIDS-associated lymphoma and endemic Burkitt lymphomas: Implications for their pathogenesis

International Nuclear Information System (INIS)

Haluska, F.G.; Russo, G.; Croce, C.M.; Kant, J.; Andreef, M.

1989-01-01

Non-Hodgkin lymphoma is a common feature of AIDS. Approximately 30-40% of these tumors exhibit clinical features suggestive of endemic Burkitt lymphoma: they are aggressive malignancies that occur in association with Epstein-Barr virus infection, they arise in the setting of immunosuppression, and they carry t(8;14) translocations without detectable rearrangement of the MYC oncogene. To understand the molecular basis of these parallels, the authors analyzed a case of Epstein-Barr-positive AIDS-associated undifferentiated lymphoma. Southern blots show that the tumor exhibits immunoglobulin joining segment rearrangement but no rearrangement of the MYC oncogene. Cloning of the rearranged joining segment allowed the isolation of recombinant clones encompassing the translocation breakpoint, and sequencing of the translocation junction disclosed that the breakpoint is situated 7 base pairs from the chromosome 14 site involved in a previously described endemic Burkitt lymphoma translocation. Furthermore, the breakpoint is situated far from MYC on chromosome 8, a constant finding in endemic Burkitt lymphomas. That the molecular architecture of the translocation in this case is strikingly similar to previously analyzed translocations from endemic Burkitt lymphomas strongly suggests that common molecular mechanisms must be operative in the pathogenesis of these tumors

Advances in Virus-Directed Therapeutics against Epstein-Barr Virus-Associated Malignancies

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Sajal K. Ghosh

2012-01-01

Full Text Available Epstein-Barr virus (EBV is the causal agent in the etiology of Burkitt’s lymphoma and nasopharyngeal carcinoma and is also associated with multiple human malignancies, including Hodgkin’s and non-Hodgkin’s lymphoma, and posttransplantation lymphoproliferative disease, as well as sporadic cancers of other tissues. A causal relationship of EBV to these latter malignancies remains controversial, although the episomic EBV genome in most of these cancers is clonal, suggesting infection very early in the development of the tumor and a possible role for EBV in the genesis of these diseases. Furthermore, the prognosis of these tumors is invariably poor when EBV is present, compared to their EBV-negative counterparts. The physical presence of EBV in these tumors represents a potential “tumor-specific” target for therapeutic approaches. While treatment options for other types of herpesvirus infections have evolved and improved over the last two decades, however, therapies directed at EBV have lagged. A major constraint to pharmacological intervention is the shift from lytic infection to a latent pattern of gene expression, which persists in those tumors associated with the virus. In this paper we provide a brief account of new virus-targeted therapeutic approaches against EBV-associated malignancies.

Therapeutic options in peripheral T cell lymphoma

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Yaping Zhang

2016-04-01

Full Text Available Abstract Peripheral T cell lymphoma (PTCL is a rare and heterogeneous group of non-Hodgkin lymphomas with a very poor prognosis. The standard first-line treatments have resulted in unsatisfactory patient outcomes. With the exception of low-risk anaplastic lymphoma kinase (ALK-positive anaplastic large cell lymphoma (ALCL, the majority of patients relapse rapidly; the current 5-year overall survival rates are only 10–30 %. Novel targeted therapies and combination chemotherapies are required for the treatment of patients with PTCL. In recent years, some retrospective and prospective studies have been performed concerning PTCL. Consequently, a number of novel agents and their relevant combination therapies have been identified, including histone deacetylase inhibitors, immunoconjugates, antifolates, monoclonal antibodies, immunomodulatory agents, nucleoside analogs, proteasome inhibitors, kinase inhibitors, bendamustine, l-asparaginase, and other targeted agents. It is hoped that these innovative approaches will finally improve outcomes in patients with PTCL. This review summarizes the currently available approaches for the treatment of PTCL with an emphasis on potential new agents, including the role of stem cell transplantation.

The Four types of Tregs in malignant lymphomas

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Wang Jing

2011-12-01

Full Text Available Abstract Regulatory T cells (Tregs are a specialized subpopulation of CD4+ T cells, which act to suppress the activation of other immune cells. Tregs represent important modulators for the interaction between lymphomas and host microenvironment. Lymphomas are a group of serious and frequently fatal malignant diseases of lymphocytes. Recent studies revealed that some lymphoma T cells might adopt a Treg profile. Assessment of Treg phenotypes and genotypes in patients may offer prediction of outcome in many types of lymphomas including diffuse large B-cell lymphoma, follicular lymphoma, cutaneous T cell lymphoma, and Hodgkin's lymphoma. Based on characterized roles of Tregs in lymphomas, we can categorize the various roles into four groups: (a suppressor Tregs; (b malignant Tregs; (c direct tumor-killing Tregs; and (d incompetent Tregs. The classification into four groups is significant in predicting prognosis and designing Tregs-based immunotherapies for treating lymphomas. In patients with lymphomas where Tregs serve either as suppressor Tregs or malignant Tregs, anti-tumor cytotoxicity is suppressed thus decreased numbers of Tregs are associated with a good prognosis. In contrast, in patients with lymphomas where Tregs serve as tumor-killing Tregs and incompetent Tregs, anti-tumor cytotoxicity is enhanced or anti-autoimmune Tregs activities are weakened thus increased numbers of Tregs are associated with a good prognosis and reduced numbers of Tregs are associated with a poor prognosis. However, the mechanisms underlying the various roles of Tregs in patients with lymphomas remain unknown. Therefore, further research is needed in this regard as well as the utility of Tregs as prognostic factors and therapy strategies in different lymphomas.

Tofacitinib induces G1 cell-cycle arrest and inhibits tumor growth in Epstein-Barr virus-associated T and natural killer cell lymphoma cells.

Science.gov (United States)

Ando, Shotaro; Kawada, Jun-Ichi; Watanabe, Takahiro; Suzuki, Michio; Sato, Yoshitaka; Torii, Yuka; Asai, Masato; Goshima, Fumi; Murata, Takayuki; Shimizu, Norio; Ito, Yoshinori; Kimura, Hiroshi

2016-11-22

Epstein-Barr virus (EBV) infects not only B cells, but also T cells and natural killer (NK) cells, and is associated with T or NK cell lymphoma. These lymphoid malignancies are refractory to conventional chemotherapy. We examined the activation of the JAK3/STAT5 pathway in EBV-positive and -negative B, T and NK cell lines and in cell samples from patients with EBV-associated T cell lymphoma. We then evaluated the antitumor effects of the selective JAK3 inhibitor, tofacitinib, against these cell lines in vitro and in a murine xenograft model. We found that all EBV-positive T and NK cell lines and patient samples tested displayed activation of the JAK3/STAT5 pathway. Treatment of these cell lines with tofacitinib reduced the levels of phospho-STAT5, suppressed proliferation, induced G1 cell-cycle arrest and decreased EBV LMP1 and EBNA1 expression. An EBV-negative NK cell line was also sensitive to tofacitinib, whereas an EBV-infected NK cell line was more sensitive to tofacitinib than its parental line. Tofacitinib significantly inhibited the growth of established tumors in NOG mice. These findings suggest that tofacitinib may represent a useful therapeutic agent for patients with EBV-associated T and NK cell lymphoma.

A Case of Diffuse Large B-Cell Lymphoma Mimicking Primary Effusion Lymphoma-Like Lymphoma

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Daisuke Usuda

2017-11-01

Full Text Available A 93-year-old female was transferred to the emergency ward of our hospital due to disturbance of consciousness and hypotension. Computed tomography showed bilateral pleural and pericardial effusion without evidence of tumor masses or lymphadenopathy. Cytodiagnosis of pleural effusion revealed proliferation of atypical lymphoid-like cells with pan-B surface markers. We suspected primary effusion lymphoma-like lymphoma; however, the monoclonality of these cells was not confirmed. Cytodiagnosis of bone marrow revealed lymphoma cells with monoclonal B-cell markers. These findings prompted a diagnosis of diffuse large B-cell lymphoma with bone marrow invasion. In the case of pericardial or pleural effusion, clinicians should consider carefully both hematological malignancy and its classification.

Spleen tyrosine kinase (Syk), a novel target of curcumin, is required for B lymphoma growth.

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Gururajan, Murali; Dasu, Trivikram; Shahidain, Seif; Jennings, C Darrell; Robertson, Darrell A; Rangnekar, Vivek M; Bondada, Subbarao

2007-01-01

Curcumin (diferuloylmethane), a component of dietary spice turmeric (Curcuma longa), has been shown in recent studies to have therapeutic potential in the treatment of cancer, diabetes, arthritis, and osteoporosis. We investigated the ability of curcumin to modulate the growth of B lymphomas. Curcumin inhibited the growth of both murine and human B lymphoma in vitro and murine B lymphoma in vivo. We also demonstrate that curcumin-mediated growth inhibition of B lymphoma is through inhibition of the survival kinase Akt and its key target Bad. However, in vitro kinase assays show that Akt is not a direct target of curcumin. We identified a novel target for curcumin in B lymphoma viz spleen tyrosine kinase (Syk). Syk is constitutively activated in primary tumors and B lymphoma cell lines and curcumin down-modulates Syk activity accompanied by down-regulation of Akt activation. Moreover, we show that overexpression of Akt, a target of Syk, or Bcl-x(L), a target of Akt can overcome curcumin-induced apoptosis of B lymphoma cells. These observations suggest a novel growth promoting role for Syk in lymphoma cells.

Anomalous expression of Thy1 (CD90) in B-cell lymphoma cells and proliferation inhibition by anti-Thy1 antibody treatment

International Nuclear Information System (INIS)

Ishiura, Yoshihito; Kotani, Norihiro; Yamashita, Ryusuke; Yamamoto, Harumi; Kozutsumi, Yasunori; Honke, Koichi

2010-01-01

The anti-CD20 monoclonal antibody (Ab) rituximab is accepted to be an effective therapeutic Ab for malignant B-cell lymphoma; however, discovery of other cell surface antigens is required for the option of antibody medicine. Considering that many tumor-associated antigens are glycans, we have searched glycoconjugates for the candidate antigens that therapeutic Abs target. To this end, we first focused on the difference in the glycogenes expression in terms of Epstein-Barr virus (EBV) infection of a Burkitt's lymphoma cell line, Akata. Using DNA array, flow cytometry and Western blotting, we found that Thy1 was highly expressed in EBV-positive Akata cells. Subsequently, Thy1 was found to be expressed in other B-cell lymphoma cell lines: BJAB, MutuI, and MutuIII, irrespective of EBV infection. Treatment of these cells with an anti-Thy1 monoclonal antibody inhibited proliferation more strongly than the therapeutic Ab rituximab. The B-cell lymphoma cell lines were classified based on the extent of the proliferation inhibition, which was not correlated with the expression level of Thy1. It is suggested that stable residence of receptor tyrosine kinases in lipid rafts sustains cell growth in B-cell lymphoma cells.

Radiotherapy for the primary ocular adnexal lymphoma

International Nuclear Information System (INIS)

Yu Dahai; Sun Sanyuan; Zhuo Shichao; Wang Haiwei

2007-01-01

Objective: To study the pathological and clinical characteristics of primary lymphoma of ocular adnexae, analyze the treatment results and discuss the methods to prevent radiation complications. Methods: From Feb. 1995 to Feb. 2004, 25 patients with primary ocular adnexal lymphoma were treated in the second hospital and the forth hospital of Xuzhou, including 11 males and 14 females. The diagnosis was confirmed pathologically by biopsy in 19 patients and lumpectomy in 6 patients, including 22 mucosa-associated lymphoid tissue (MALT) lymphoma and 3 non-MALT lymphoma. According to the Ann Arbor Staging System, there were 21 patients with tumor in stage I E, 3 in stage II E and 1 in stage III E. The primary tumor was found in the eyelid or conjunctiva in 19 eyes and orbit in 9 eyes. Radiotherapy were given to 22 patients (25 eyes) by deep X-rays, 60 Co γ-rays or mixed beams. The total irradiation dose ranged from 30.0 to 57.6 Gy. Kaplan-Meier method was used to calculate the survival rate and Logrank test was used to detect the difference between the different groups. Results: The 5-, 10-year accumulated survival rates (SR) of the whole group were 90% and 82%. The 10-year SR of patients with primary, eyelid or conjunctiva tumor and orbit tumor were 100% and 58% (P=0.032). The local control rates of the radiotherapy group and non-radiotherapy group were 92% and 33 % (P=0.006). The 10-year SR of patients with tumor completely removed and those with residues were 83% and 82% (P=0.907). The 10-year SR of MALT lymphoma and non-MALT lymphoma were 90.0% and 33.3% (P=0.009). After radiotherapy, 8 eyes (36%) had cataract formation and 7 eyes (28%) had xerophalmic symptoms. Conclusions: The results of radiothera- py for the primary ocular adnexal lymphoma are satisactory. The prognosis of patients with primary, eyelid or conjunctiva tumor is better than those with orbit tumor. The vast majority of the primary ocular adnexal lymphomas are MALT lymphomas. The survival rate of

Analysis of perfusion weighted image of CNS lymphoma

International Nuclear Information System (INIS)

Lee, In Ho; Kim, Sung Tae; Kim, Hyung-Jin; Kim, Keon Ha; Jeon, Pyoung; Byun, Hong Sik

2010-01-01

Purpose: It is difficult to differentiate CNS lymphoma from other tumors such as malignant gliomas, metastases, or meningiomas with conventional MR imaging, because the imaging findings are overlapped between these tumors. The purpose of this study is to investigate the perfusion weighted MR imaging findings of CNS lymphomas and to compare the relative cerebral blood volume ratios between CNS lymphomas and other tumors such as high grade gliomas, metastases, or meningiomas. Materials and methods: We retrospectively reviewed MRI findings and clinical records in 13 patients with pathologically proven CNS lymphoma between January 2006 and November 2008. We evaluated the relative cerebral blood volume ratios of tumor, which were obtained by dividing the values obtained from the normal white matter on MRI. Results: Total 13 patients (M:F = 8:5; age range 46-67 years, mean age 52.3 years) were included. The CNS lymphomas showed relatively low values of maximum relative CBV ratio in most patients regardless of primary or secondary CNS lymphoma. Conclusion: Perfusion weighted image may be helpful in the diagnosis of CNS lymphoma in spite of primary or secondary or B cell or T cell.

NKT cell adjuvant-based tumor vaccine for treatment of myc oncogene-driven mouse B-cell lymphoma

NARCIS (Netherlands)

Mattarollo, Stephen R.; West, Alison C.; Steegh, Kim; Duret, Helene; Paget, Christophe; Martin, Ben; Matthews, Geoffrey M.; Shortt, Jake; Chesi, Marta; Bergsagel, P. Leif; Bots, Michael; Zuber, Johannes; Lowe, Scott W.; Johnstone, Ricky W.; Smyth, Mark J.

2012-01-01

Immunomodulators are effective in controlling hematologic malignancy by initiating or reactivating host antitumor immunity to otherwise poorly immunogenic and immune suppressive cancers. We aimed to boost antitumor immunity in B-cell lymphoma by developing a tumor cell vaccine incorporating

Clinical Significance of "Double-hit" and "Double-protein" expression in Primary Gastric B-cell Lymphomas.

Science.gov (United States)

He, Miaoxia; Chen, Keting; Li, Suhong; Zhang, Shimin; Zheng, Jianming; Hu, Xiaoxia; Gao, Lei; Chen, Jie; Song, Xianmin; Zhang, Weiping; Wang, Jianmin; Yang, Jianmin

2016-01-01

Primary gastric B-cell lymphoma is the second most common malignancy of the stomach. There are many controversial issues about its diagnosis, treatment and clinical management. "Double-hit" and "double-protein" involving gene rearrangement and protein expression of c-Myc and bcl2/bcl6 are the most used terms to describe DLBCL poor prognostic factors in recent years. However, very little is known about the role of these prognostic factors in primary gastric B-cell lymphomas. This study aims to obtain a molecular pathology prognostic model of gastric B-cell lymphoma for clinical stratified management by evaluating how the "double-hit" and "double-protein" in tumor cells as well as microenvironmental reaction of tumor stromal tissue affect clinical outcome in primary gastric B-cell lymphomas. Data and tissues of 188 cases diagnosed with gastric B-cell lymphomas were used in this study. Tumor tissue microarray (TMA) of formalin fixed and paraffin embedded (FFPE) tissues was constructed for fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) analysis with a serial of biomarkers containing MYC, BCL2, BCL6, CD31, SPARC, CD10, MUM1 and Ki-67. Modeled period analysis was used to estimate 3-year and 5-year overall survival (OS) and disease-free survival (DFS) distributions. There was no definite "double-hit" case though the gene rearrangement of c-Myc (5.9%), bcl2 (0.1%) and bcl6 (7.4%) was found in gastric B-cell lymphomas. The gene amplification or copy gains of c-Myc (10.1%), bcl-2 (17.0%) and bcl-6 (0.9%) were present in these lymphomas. There were 12 cases of the lymphomas with the "double-protein" expression of MYC and BCL2/BCL6. All patients with "double-protein" gastric B-cell lymphomas had poor outcome compared with those without. More importantly, "MYC-BCL2-BCL6" negative group of gastric B-cell lymphoma patients had favorable clinical outcome regardless clinical stage, pathological types and therapeutic modalities. And the similar better

Epstein–Barr Virus-Induced Metabolic Rearrangements in Human B-Cell Lymphomas

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Pier P. Piccaluga

2018-06-01

Full Text Available Tumor metabolism has been the object of several studies in the past, leading to the pivotal observation of a consistent shift toward aerobic glycolysis (so-called Warburg effect. More recently, several additional investigations proved that tumor metabolism is profoundly affected during tumorigenesis, including glucose, lipid and amino-acid metabolism. It is noticeable that metabolic reprogramming can represent a suitable therapeutic target in many cancer types. Epstein–Barr virus (EBV was the first virus linked with cancer in humans when Burkitt lymphoma (BL was described. Besides other well-known effects, it was recently demonstrated that EBV can induce significant modification in cell metabolism, which may lead or contribute to neoplastic transformation of human cells. Similarly, virus-induced tumorigenesis is characterized by relevant metabolic abnormalities directly induced by the oncoviruses. In this article, the authors critically review the most recent literature concerning EBV-induced metabolism alterations in lymphomas.

NKT Cell Responses to B Cell Lymphoma.

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Li, Junxin; Sun, Wenji; Subrahmanyam, Priyanka B; Page, Carly; Younger, Kenisha M; Tiper, Irina V; Frieman, Matthew; Kimball, Amy S; Webb, Tonya J

2014-06-01

Natural killer T (NKT) cells are a unique subset of CD1d-restricted T lymphocytes that express characteristics of both T cells and natural killer cells. NKT cells mediate tumor immune-surveillance; however, NKT cells are numerically reduced and functionally impaired in lymphoma patients. Many hematologic malignancies express CD1d molecules and co-stimulatory proteins needed to induce anti-tumor immunity by NKT cells, yet most tumors are poorly immunogenic. In this study, we sought to investigate NKT cell responses to B cell lymphoma. In the presence of exogenous antigen, both mouse and human NKT cell lines produce cytokines following stimulation by B cell lymphoma lines. NKT cell populations were examined ex vivo in mouse models of spontaneous B cell lymphoma, and it was found that during early stages, NKT cell responses were enhanced in lymphoma-bearing animals compared to disease-free animals. In contrast, in lymphoma-bearing animals with splenomegaly and lymphadenopathy, NKT cells were functionally impaired. In a mouse model of blastoid variant mantle cell lymphoma, treatment of tumor-bearing mice with a potent NKT cell agonist, α-galactosylceramide (α-GalCer), resulted in a significant decrease in disease pathology. Ex vivo studies demonstrated that NKT cells from α-GalCer treated mice produced IFN-γ following α-GalCer restimulation, unlike NKT cells from vehicle-control treated mice. These data demonstrate an important role for NKT cells in the immune response to an aggressive hematologic malignancy like mantle cell lymphoma.

A Whole-Tumor Histogram Analysis of Apparent Diffusion Coefficient Maps for Differentiating Thymic Carcinoma from Lymphoma.

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Zhang, Wei; Zhou, Yue; Xu, Xiao-Quan; Kong, Ling-Yan; Xu, Hai; Yu, Tong-Fu; Shi, Hai-Bin; Feng, Qing

2018-01-01

To assess the performance of a whole-tumor histogram analysis of apparent diffusion coefficient (ADC) maps in differentiating thymic carcinoma from lymphoma, and compare it with that of a commonly used hot-spot region-of-interest (ROI)-based ADC measurement. Diffusion weighted imaging data of 15 patients with thymic carcinoma and 13 patients with lymphoma were retrospectively collected and processed with a mono-exponential model. ADC measurements were performed by using a histogram-based and hot-spot-ROI-based approach. In the histogram-based approach, the following parameters were generated: mean ADC (ADC mean ), median ADC (ADC median ), 10th and 90th percentile of ADC (ADC 10 and ADC 90 ), kurtosis, and skewness. The difference in ADCs between thymic carcinoma and lymphoma was compared using a t test. Receiver operating characteristic analyses were conducted to determine and compare the differentiating performance of ADCs. Lymphoma demonstrated significantly lower ADC mean , ADC median , ADC 10 , ADC 90 , and hot-spot-ROI-based mean ADC than those found in thymic carcinoma (all p values histogram analysis of ADC maps can improve the differentiating performance between thymic carcinoma and lymphoma.

Breast systemic follicular lymphoma in a man: a case report

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La Mantia Elvira

2012-07-01

Full Text Available Abstract Introduction Breast involvement by non-Hodgkin lymphoma is particularly rare in men. We describe the case of a patient with a rapidly growing, painless gynecomastia-like nodule in the left breast. On ultrasonography, the nodule was suspicious for breast carcinoma. Case presentation A breast biopsy from a 54-year-old Caucasian man showed the morphoimmunophenotypical features of grade 3 follicular lymphoma. Moreover, fluorescence in situ hybridization analysis showed a t(14,18 translocation suggesting breast involvement by a systemic lymphoma rather than a primary breast lymphoma. The histological diagnosis was subsequently confirmed after nodule excision. Mediastinal and abdominal node involvement was then identified on computed tomography and positron emission tomography scans during staging examinations. Our patient was treated with chemotherapy. After three years our patient experienced a right retro-areolar relapse. He then received two further cycles of chemotherapy but developed a myeloid acute leukemia and, as a result of this, he subsequently died. Conclusions The rarity of breast lymphomas, especially in men, and the problems related to the therapeutic choices with these tumors require molecular techniques in association with classical histological diagnosis.

Primary CNS lymphoma in nonimmunocompromised patients magnetic resonance study

International Nuclear Information System (INIS)

Pena, J.; Fernandez, J.M.; Galarraga, M.I.; Pozo, A.; Montes, A.; Ablanedo, P.

1995-01-01

Prymary lymphoma of the CNS (PLCNS) is a relatively infrequent malignant tumor that has become increasingly common over the past decade. The radiological signs, although not pathognomonic, are quite specific and suggestive of the correct diagnosis, thus facilitating therapeutic management. We present six cases of PLCNS in nonimmunocopromised patients studied by MR in our hospital over the past two and a half years. We describe theradiological findings, correlating them with those mentioned in the literature. 14 refs

Radiotherapy-induced anti-tumor immunity contributes to the therapeutic efficacy of irradiation and can be augmented by CTLA-4 blockade in a mouse model.

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Yuya Yoshimoto

Full Text Available PURPOSE: There is growing evidence that tumor-specific immune responses play an important role in anti-cancer therapy, including radiotherapy. Using mouse tumor models we demonstrate that irradiation-induced anti-tumor immunity is essential for the therapeutic efficacy of irradiation and can be augmented by modulation of cytotoxic T lymphocyte (CTL activity. METHODS AND MATERIALS: C57BL/6 mice, syngeneic EL4 lymphoma cells, and Lewis lung carcinoma (LL/C cells were used. Cells were injected into the right femurs of mice. Ten days after inoculation, tumors were treated with 30 Gy of local X-ray irradiation and their growth was subsequently measured. The effect of irradiation on tumor growth delay (TGD was defined as the time (in days for tumors to grow to 500 mm3 in the treated group minus that of the untreated group. Cytokine production and serum antibodies were measured by ELISA and flow cytometry. RESULTS: In the EL4 tumor model, tumors were locally controlled by X-ray irradiation and re-introduced EL4 cells were completely rejected. Mouse EL4-specific systemic immunity was confirmed by splenocyte cytokine production and detection of tumor-specific IgG1 antibodies. In the LL/C tumor model, X-ray irradiation also significantly delayed tumor growth (TGD: 15.4 days and prolonged median survival time (MST to 59 days (versus 28 days in the non-irradiated group. CD8(+ cell depletion using an anti-CD8 antibody significantly decreased the therapeutic efficacy of irradiation (TGD, 8.7 days; MST, 49 days. Next, we examined whether T cell modulation affected the efficacy of radiotherapy. An anti-CTLA-4 antibody significantly increased the anti-tumor activity of radiotherapy (TGD was prolonged from 13.1 to 19.5 days, while anti-FR4 and anti-GITR antibodies did not affect efficacy. CONCLUSIONS: Our results indicate that tumor-specific immune responses play an important role in the therapeutic efficacy of irradiation. Immunomodulation, including CTLA-4

Radiotherapy-Induced Anti-Tumor Immunity Contributes to the Therapeutic Efficacy of Irradiation and Can Be Augmented by CTLA-4 Blockade in a Mouse Model

Science.gov (United States)

Yoshimoto, Yuya; Suzuki, Yoshiyuki; Mimura, Kousaku; Ando, Ken; Oike, Takahiro; Sato, Hiro; Okonogi, Noriyuki; Maruyama, Takanori; Izawa, Shinichiro; Noda, Shin-ei; Fujii, Hideki; Kono, Koji; Nakano, Takashi

2014-01-01

Purpose There is growing evidence that tumor-specific immune responses play an important role in anti-cancer therapy, including radiotherapy. Using mouse tumor models we demonstrate that irradiation-induced anti-tumor immunity is essential for the therapeutic efficacy of irradiation and can be augmented by modulation of cytotoxic T lymphocyte (CTL) activity. Methods and Materials C57BL/6 mice, syngeneic EL4 lymphoma cells, and Lewis lung carcinoma (LL/C) cells were used. Cells were injected into the right femurs of mice. Ten days after inoculation, tumors were treated with 30 Gy of local X-ray irradiation and their growth was subsequently measured. The effect of irradiation on tumor growth delay (TGD) was defined as the time (in days) for tumors to grow to 500 mm3 in the treated group minus that of the untreated group. Cytokine production and serum antibodies were measured by ELISA and flow cytometry. Results In the EL4 tumor model, tumors were locally controlled by X-ray irradiation and re-introduced EL4 cells were completely rejected. Mouse EL4-specific systemic immunity was confirmed by splenocyte cytokine production and detection of tumor-specific IgG1 antibodies. In the LL/C tumor model, X-ray irradiation also significantly delayed tumor growth (TGD: 15.4 days) and prolonged median survival time (MST) to 59 days (versus 28 days in the non-irradiated group). CD8(+) cell depletion using an anti-CD8 antibody significantly decreased the therapeutic efficacy of irradiation (TGD, 8.7 days; MST, 49 days). Next, we examined whether T cell modulation affected the efficacy of radiotherapy. An anti-CTLA-4 antibody significantly increased the anti-tumor activity of radiotherapy (TGD was prolonged from 13.1 to 19.5 days), while anti-FR4 and anti-GITR antibodies did not affect efficacy. Conclusions Our results indicate that tumor-specific immune responses play an important role in the therapeutic efficacy of irradiation. Immunomodulation, including CTLA-4 blockade, may be a

[Bilateral ovarian Burkitt's lymphoma. A case presentation].

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Briseño-Hernández, Andrés Alejandro; Quezada-López, Deissy Roxana; Castañeda-Chávez, Agar; Dassaejv Macías-Amezcua, Michel; Pintor-Belmontes, Julio Cesar

2014-01-01

Burkitt lymphoma, is described as an aggressive form of non-Hodgkin lymphoma of B cells which occurs most often in children and young adults, ovarian lymphoma can appear as a primary lesion or more commonly referred to as a metastasis. Primary ovarian lesions are rare manifestations corresponding to 0.5% of non-Hodgkin lymphoma and 1.5% of ovarian tumors. Clinic case: 31 years old female with general weakness, march incapacity, dyspnea, hyporexia, fever, diaphoresis, weight loss of 20 kg, flat abs with abdominal pain; Ca125 610 U/ml. Abdominal computed tomography shows a solid aspect tumor which affects the right pelvic cavity. Bilateral ovarian tumors were removed. Microscopically, both lesions show a "starry sky" pattern composed by a monotonous infiltration of lymphocytes mixed with large and clear macrophages, several atypical mitoses, and necrosis and hemorrhage areas. Immunohistochemistry was positive for CD10, CD20, and negative for CD3 and high Ki67 proliferation index. Bilateral ovarian Burkitt's lymphoma was diagnosed. Bilateral ovarian Burkitt's lymphoma is a rare entity, with a variability of presentations, the abdominal pain and abdominal tumors are the most frequent. The patient's prognosis at short term is poor, therefore it's necessary to know this entity and make an early diagnosis.

Rituximab Treatment Prevents Lymphoma Onset in Gastric Cancer Patient-Derived Xenografts

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Simona Corso

2018-05-01

Full Text Available Patient-Derived Xenografts (PDXs, entailing implantation of cancer specimens in immunocompromised mice, are emerging as a valuable translational model that could help validate biologically relevant targets and assist the clinical development of novel therapeutic strategies for gastric cancer.More than 30% of PDXs generated from gastric carcinoma samples developed human B-cell lymphomas instead of gastric cancer. These lymphomas were monoclonal, Epstein Barr Virus (EBV positive, originated tumorigenic cell cultures and displayed a mutational burden and an expression profile distinct from gastric adenocarcinomas. The ability of grafted samples to develop lymphomas did not correlate with patient outcome, nor with the histotype, the lymphocyte infiltration level, or the EBV status of the original gastric tumor, impeding from foreseeing lymphoma onset. Interestingly, lymphoma development was significantly more frequent when primary rather than metastatic samples were grafted.Notably, the development of such lympho-proliferative disease could be prevented by a short rituximab treatment upon mice implant, without negatively affecting gastric carcinoma engraftment.Due to the high frequency of human lymphoma onset, our data show that a careful histologic analysis is mandatory when generating gastric cancer PDXs. Such care would avoid misleading results that could occur if testing of putative gastric cancer therapies is performed in lymphoma PDXs. We propose rituximab treatment of mice to prevent lymphoma development in PDX models, averting the loss of human-derived samples.

Efficient gene transfer into lymphoma cells using adenoviral vectors combined with lipofection.

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Buttgereit, P; Weineck, S; Röpke, G; Märten, A; Brand, K; Heinicke, T; Caselmann, W H; Huhn, D; Schmidt-Wolf, I G

2000-08-01

Tumor cells, such as lymphoma cells, are possible targets for gene therapy. In general, gene therapeutic approaches require efficient gene transfer to host cells and sufficient transgene expression. However, lymphoma cells previously have been demonstrated to be resistant to most of the currently available gene transfer methods. The aim of this study was to analyze various methods for transfection of lymphoma cells and to improve the efficiency of gene delivery. In accordance with previously published reports, lymphoma cells were demonstrated to be resistant to lipofection and electroporation. In contrast, we present an improved adenoviral protocol leading to highly efficient gene transfer to lymphoma cell lines derived from B cells as well as primary lymphoma cells being achieved with an adenoviral vector system encoding the beta-galactosidase protein. At a multiplicity of infection of 200, up to 100% of Daudi cells and Raji cells and 70% of OCI-Ly8-LAM53 cells could be transfected. Even at high adenoviral concentrations, no marked toxicity was observed, and the growth characteristics of the lymphoma cell lines were not impaired. The transfection rates in primary cells derived from six patients with non-Hodgkin's lymphoma were 30-65%, respectively. Transfection efficiency could be further increased by addition of cationic liposomes to adenoviral gene transfer. Furthermore, we examined the expression of the Coxsackie-adenoviral receptor (CAR) and the integrin receptors on the lymphoma cell surface. Flow cytometric analysis showed that 88% of Daudi cells, 69% of Raji cells, and 6% of OCI-Ly8-LAM53 cells expressed CAR on the cell surface. According to our data, adenoviral infection of lymphoma cells seems to be mediated by CAR. In contrast, integrin receptors are unlikely to play a major role, because lymphoma cells were negative for alphavbeta3-integrins and negative for alphavbeta5-integrins. In conclusion, this study demonstrates that B-lymphoma cell lines and

Lymphoma: Immune Evasion Strategies

International Nuclear Information System (INIS)

Upadhyay, Ranjan; Hammerich, Linda; Peng, Paul; Brown, Brian; Merad, Miriam; Brody, Joshua D.

2015-01-01

While the cellular origin of lymphoma is often characterized by chromosomal translocations and other genetic aberrations, its growth and development into a malignant neoplasm is highly dependent upon its ability to escape natural host defenses. Neoplastic cells interact with a variety of non-malignant cells in the tumor milieu to create an immunosuppressive microenvironment. The resulting functional impairment and dysregulation of tumor-associated immune cells not only allows for passive growth of the malignancy but may even provide active growth signals upon which the tumor subsequently becomes dependent. In the past decade, the success of immune checkpoint blockade and adoptive cell transfer for relapsed or refractory lymphomas has validated immunotherapy as a possible treatment cornerstone. Here, we review the mechanisms by which lymphomas have been found to evade and even reprogram the immune system, including alterations in surface molecules, recruitment of immunosuppressive subpopulations, and secretion of anti-inflammatory factors. A fundamental understanding of the immune evasion strategies utilized by lymphomas may lead to better prognostic markers and guide the development of targeted interventions that are both safer and more effective than current standards of care

Lymphoma: Immune Evasion Strategies

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Upadhyay, Ranjan; Hammerich, Linda; Peng, Paul [Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Brown, Brian [Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Merad, Miriam [Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Brody, Joshua D., E-mail: joshua.brody@mssm.edu [Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States)

2015-04-30

While the cellular origin of lymphoma is often characterized by chromosomal translocations and other genetic aberrations, its growth and development into a malignant neoplasm is highly dependent upon its ability to escape natural host defenses. Neoplastic cells interact with a variety of non-malignant cells in the tumor milieu to create an immunosuppressive microenvironment. The resulting functional impairment and dysregulation of tumor-associated immune cells not only allows for passive growth of the malignancy but may even provide active growth signals upon which the tumor subsequently becomes dependent. In the past decade, the success of immune checkpoint blockade and adoptive cell transfer for relapsed or refractory lymphomas has validated immunotherapy as a possible treatment cornerstone. Here, we review the mechanisms by which lymphomas have been found to evade and even reprogram the immune system, including alterations in surface molecules, recruitment of immunosuppressive subpopulations, and secretion of anti-inflammatory factors. A fundamental understanding of the immune evasion strategies utilized by lymphomas may lead to better prognostic markers and guide the development of targeted interventions that are both safer and more effective than current standards of care.

Anomalous expression of Thy1 (CD90) in B-cell lymphoma cells and proliferation inhibition by anti-Thy1 antibody treatment

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Ishiura, Yoshihito [Department of Biochemistry, Kochi University Medical School, Kohasu, Okocho, Nankoku, Kochi 783-8505 (Japan); CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Kotani, Norihiro, E-mail: kotani@kochi-u.ac.jp [CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Kochi System Glycobiology Center, Kochi University Medical School, Kohasu, Okocho, Nankoku, Kochi 783-8505 (Japan); Yamashita, Ryusuke [Department of Biochemistry, Kochi University Medical School, Kohasu, Okocho, Nankoku, Kochi 783-8505 (Japan); CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Yamamoto, Harumi [Laboratory of Membrane Biochemistry and Biophysics, Graduate School of Biostudies, Kyoto University, Yoshida Shimo-Adachi, Sakyo, Kyoto 606-8501 (Japan); Kozutsumi, Yasunori [CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Laboratory of Membrane Biochemistry and Biophysics, Graduate School of Biostudies, Kyoto University, Yoshida Shimo-Adachi, Sakyo, Kyoto 606-8501 (Japan); Honke, Koichi [Department of Biochemistry, Kochi University Medical School, Kohasu, Okocho, Nankoku, Kochi 783-8505 (Japan); CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Kochi System Glycobiology Center, Kochi University Medical School, Kohasu, Okocho, Nankoku, Kochi 783-8505 (Japan)

2010-05-28

The anti-CD20 monoclonal antibody (Ab) rituximab is accepted to be an effective therapeutic Ab for malignant B-cell lymphoma; however, discovery of other cell surface antigens is required for the option of antibody medicine. Considering that many tumor-associated antigens are glycans, we have searched glycoconjugates for the candidate antigens that therapeutic Abs target. To this end, we first focused on the difference in the glycogenes expression in terms of Epstein-Barr virus (EBV) infection of a Burkitt's lymphoma cell line, Akata. Using DNA array, flow cytometry and Western blotting, we found that Thy1 was highly expressed in EBV-positive Akata cells. Subsequently, Thy1 was found to be expressed in other B-cell lymphoma cell lines: BJAB, MutuI, and MutuIII, irrespective of EBV infection. Treatment of these cells with an anti-Thy1 monoclonal antibody inhibited proliferation more strongly than the therapeutic Ab rituximab. The B-cell lymphoma cell lines were classified based on the extent of the proliferation inhibition, which was not correlated with the expression level of Thy1. It is suggested that stable residence of receptor tyrosine kinases in lipid rafts sustains cell growth in B-cell lymphoma cells.

[Exceptional etiology of acute renal: Burkitt's lymphoma].

Science.gov (United States)

Dial, Cherif; Doh, Kwame; Thiam, Ibou; Faye, Mariam; Woto-Gaye, Gisèle

2018-02-05

Burkitt's lymphoma (BL) is an exceptional cause of acute renal failure (ARF). The origin of the tumor clone may be lymphoid follicles secondary to renal Epstein-Barr virus (EBV) infection. With the presentation of this clinical case, the pathogenesis, diagnostic criteria and evolution of this extremely rare affection will be discussed. A 4-year-old patient with a recent history of acute osteomyelitis of the right thigh presented an ARF without indications of post-infectious glomerulonephritis. Ultrasound showed enlarged kidneys without dilation of the excretory cavities. Diffuse interstitial infiltration of atypical lymphoid cells of medium size were noted upon renal biopsy. The tumor cells expressed antibodies against CD20, CD10, Bcl6, and Ki67 but not against Bcl2 or CD3. The search for an EBV infection was positive. A few days after diagnosis, the evolution was spontaneously fatal. BL of the kidney is a rare condition that accounts for less than 1 % of kidney tumors, associated almost invariably with EBV infection. The diagnosis is confirmed histologically by renal biopsy and the criteria of Malbrain affirms the primitive character of the lymphoma. BL of the kidney is a diagnostic and therapeutic emergency and may be fatal. Copyright © 2018 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.

Diagnostic imagings of malignant lymphoma of the pancreas with obstructive jaundice

International Nuclear Information System (INIS)

Shirahase, Isao; Kobayashi, Nobuaki; Tanimura, Hiroshi; Yamaoka, Yoshio; Ozawa, Kazue; Hayashi, Nobushige; Itoh, Kyo; Nakajima, Yasuaki

1987-01-01

We performed pancreatoduodenectomy in a 41-year-old man with pancreatic malignant lymphoma, who began to have obstructive jaundice and in whom imaging showed a tumor of the head of the pancreas with extrapancreatic growth. The tumor was 8 x 8.5 x 4 cm in size. The histopathological findings of the tumor indicated a malignant lymphoma, non-Hodgkin, diffuse large cell type. The patient was discharged after receiving nine courses of postoperative chemotherapy with VEPA. It is very important in determing the surgical indication to preoperatively differentiate malignant lymphoma from pancreatic cancer, since malignant lymphoma originating from the gastrointestinal organs can, in some cases, be almost completely repaired if the tumor is removed in the early stage. Thus, it is possible to achieve effective multidisciplinary treatment for malignant lymphoma by performing closer preoperative examinations and taking into consideration the possibility of the existence of malignant lymphoma. This paper discusses the details of the imaging necessary to differentiate pancreatic malignant lymphoma. (author)

Combined modality treatment improves tumor control and overall survival in patients with early stage Hodgkin's lymphoma: a systematic review

DEFF Research Database (Denmark)

Herbst, Christine; Rehan, Fareed A; Brillant, Corinne

2010-01-01

as well as conference proceedings from January 1980 to February 2009 for randomized controlled trials comparing chemotherapy alone versus the same chemotherapy regimen plus radiotherapy. Progression free survival and similar outcomes were analyzed together as tumor control. Effect measures used were......Combined modality treatment (CMT) of chemotherapy followed by localized radiotherapy is standard treatment for patients with early stage Hodgkin's lymphoma. However, the role of radiotherapy has been questioned recently and some clinical study groups advocate chemotherapy only for this indication....... We thus performed a systematic review with meta-analysis of randomized controlled trials comparing chemotherapy alone with CMT in patients with early stage Hodgkin's lymphoma with respect to response rate, tumor control and overall survival (OS). We searched Medline, EMBASE and the Cochrane Library...

Computed tomography in intracranial malignant lymphoma

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Naruse, S; Odake, G; Fujimoto, M; Yamaki, T; Mizukawa, N [Kyoto Prefectural Univ. of Medicine (Japan)

1978-09-01

Malignant lymphoma of the central nervous system has been found more and more often in recent years, partly because of the increased use of radiation and such drugs as steroids and antibiotics. However, the definite diagnosis of this disease is difficult until histological verification has been done by operation or autopsy. Since the revolutionary development of computed tomography, however, several reports have been presented, on the computed tomography of malignant lymphoma of the thorax and abdomen. Nevertheless, only a few cases of intracranial malignant lymphoma have been reported. The purpose of this paper, using four patients, is to emphasize the value of computed tomography in the diagnosis of intracranial malignant lymphoma. The characteristic CT findings of intracranial malignant lymphoma may be summarized follows: (1) the tumors are demonstrated to be well-defined, nodular-shaped, and homogenous isodensity - or slightly high-density - lesions in plain scans, and the tumors homogenously increase in density upon contrast enhancement; (2) the disease always has multifocal intracranial lesions, which are shown simultaneously or one after another, and (3) perifocal edema is prominent around the tumors in the cerebral hemisphere.

Tumor bulk as a prognostic factor for the management of localized aggressive non-Hodgkin's lymphoma: a survey of the Japan lymphoma radiation therapy group

International Nuclear Information System (INIS)

Oguchi, Masahiko; Ikeda, Hiroshi; Isobe, Kouichi; Hirota, Saeko; Hasegawa, Masatoshi; Nakamura, Katsumasa; Sasai, Keisuke; Hayabuchi, Naofumi

2000-01-01

Purpose: To identify the prognostic factors that specifically predict survival rates of patients with localized aggressive non-Hodgkin's lymphoma (NHL). Methods and Materials: The survey was carried out at 25 radiation oncology institutions in Japan in 1998. The 5-year event-free (EFS) and overall survival rates (OAS) were calculated, and univariate and multivariate analyses were done to identify which of the following factors, namely, gender, age, performance status (PS), serum lactate dehydrogenase (LDH) level, Stage (I vs. II), tumor bulk (maximum diameter), and treatment, were significant from the viewpoint of prognosis. Results: A total of 1141 patients with Stage I and II NHL were treated by the Japanese Lymphoma Radiation Therapy Group between 1988 and 1992. Of them, 787 patients, who were treated using definitive radiotherapy with or without chemotherapy for intermediate- and high-grade lymphomas in working formulation, constituted the core of this study. Primary tumors arose mainly from extranodal organs (71%) in the head and neck (Waldeyer's ring: 36% and sinonasal cavities: 9%). The factors associated with poorer prognosis were age over 60 years old (p < 0.0001), radiation therapy alone (p < 0.0001), PS = 2-4 (p = 0.0011), (sex male, p = 0.0078), a bulky tumor more than 6 cm in maximum diameter (p 0.0088), elevated LDH (p = 0.0117), and stage II (p = 0.0642). A median dose of 42 Gy was delivered mainly to the involved fields. Short-course chemotherapy was provided in 549 (70%) patients. The 5-year OAS and EFS rates for all patients were 71% and 67%, respectively. According to the stage-modified International Prognostic Index, the 5-year EFS of the patients with risk factors from 0 to 1 was 76%, 61% for patients with two risk factors, and 26% for patients with three or more risk factors. Conclusion: Extranodal presentation, especially Waldeyer's ring and sinonasal cavities, is encountered more frequently in Japan than in Western countries. Tumor bulk is

International Working Group consensus response evaluation criteria in lymphoma (RECIL 2017)

DEFF Research Database (Denmark)

Younes, A; Hilden, P; Coiffier, B

2017-01-01

of malignancies, including solid tumors and lymphoma. Furthermore, with the advances in genome sequencing, new "basket" clinical trial designs have emerged that select patients based on the presence of specific genetic alterations across different types of solid tumors and lymphoma. The standard response criteria...... enrolled on 10 multicenter clinical trials and developed new lymphoma response criteria (RECIL 2017). We demonstrate that assessment of tumor burden in lymphoma clinical trials can use the sum of longest diameters of a maximum of three target lesions. Furthermore, we introduced a new provisional category...

Extranodal marginal zone (malt type) lymphoma of the ocular adnexae: a localized tumor with favorable outcome after radiation therapy

International Nuclear Information System (INIS)

Fung, Claire Y.; Ferry, Judith A.; Linggood, Rita M.; Lucarelli, Mark J.; Daly, William; Harris, Nancy L.; Wang, C.C.

1996-01-01

common type (55%) of primary ocular adnexal lymphoma, but comprised only 19% of secondary tumors (p=0.002); follicle center lymphoma was second in frequency (22%) in primary cases but the most common lymphoma to secondarily involve the orbit (38%) (p=0.05). MALT lymphomas had a significantly higher frequency of localized disease at presentation (87%) than follicle center lymphoma (53%) (p=0.03). Moderate radiation doses resulted in 100% actuarial local control at 6 years and a 77% probability of remaining distant relapse free at 6 years in patients with localized disease. Patients with MALT lymphomas may have a lower relapse rate than those with follicle center lymphomas. Our data suggest that MALT lymphoma of the ocular adnexae is a localized tumor that may be curable with moderate doses of radiation therapy

Cutaneous double-hit B-cell lymphoma: an aggressive form of B-cell lymphoma with a propensity for cutaneous dissemination.

Science.gov (United States)

Magro, Cynthia M; Wang, Xuan; Subramaniyam, Shivakumar; Darras, Natasha; Mathew, Susan

2014-04-01

Diffuse large cell B-cell lymphoma of the skin is most commonly represented by diffuse large cell variants of primary cutaneous follicle center cell lymphoma and the leg-type lymphoma. In a minority of cases, the infiltrates are an expression of stage 4 disease of established extracutaneous B-cell lymphoma. We describe 3 patients with an aggressive form of B-cell lymphoma secondarily involving the skin. Two of the patients were in the ninth decade of life, whereas 1 patient was 34 years of age. In the elderly patients, there was an antecedent and/or concurrent history of follicular lymphoma, whereas in the younger patient, the tumor was a de novo presentation of this aggressive form of lymphoma. The elderly patients succumbed to their disease within less than a year from the time of diagnosis, whereas 1 patient is alive but with persistent and progressive disease despite chemotherapeutic intervention. The infiltrates in all 3 cases were diffuse and composed of large malignant hematopoietic cells that exhibited a round nucleus with a finely dispersed chromatin. Phenotypically, the tumor cells were Bcl-2 and CD10 positive, whereas Bcl-6 and Mum-1 showed variable positivity. One case showed combined Mum-1 positivity along with an acute lymphoblastic lymphoma phenotype, including the absence of CD20 expression. In each case, there was a c-MYC and BCL2/IGH rearrangement diagnostic of double-hit lymphoma. In one case, there was an additional BCL6 rearrangement, defining what is in essence triple-hit lymphoma. In conclusion, double-hit lymphoma is an aggressive form of B-cell neoplasia resistant to standard chemotherapy regimens, which in many but not all cases represents tumor progression in the setting of a lower grade B-cell malignancy.

Antibody or Antibody Fragments : Implications for Molecular Imaging and Targeted Therapy of Solid Tumors

NARCIS (Netherlands)

Xenaki, Katerina T; Oliveira, Sabrina; van Bergen En Henegouwen, Paul M P

2017-01-01

The use of antibody-based therapeutics has proven very promising for clinical applications in cancer patients, with multiple examples of antibodies and antibody-drug conjugates successfully applied for the treatment of solid tumors and lymphomas. Given reported recurrence rates, improvements are

The effect of age at exposure on the inactivating mechanisms and relative contributions of key tumor suppressor genes in radiation-induced mouse T-cell lymphomas

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Sunaoshi, Masaaki [Radiobiology for Children' s Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Department of Biological Sciences, College of Science, Ibaraki University, Bunkyo 2-1-1, Mito, Ibaraki 310-8512 (Japan); Amasaki, Yoshiko; Hirano-Sakairi, Shinobu; Blyth, Benjamin J. [Radiobiology for Children' s Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Morioka, Takamitsu [Radiobiology for Children' s Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Radiation Effect Accumulation and Prevention Project, Fukushima Project Headquarters, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Kaminishi, Mutsumi [Radiobiology for Children' s Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Shang, Yi [Radiation Effect Accumulation and Prevention Project, Fukushima Project Headquarters, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Nishimura, Mayumi; Shimada, Yoshiya [Radiobiology for Children' s Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Radiation Effect Accumulation and Prevention Project, Fukushima Project Headquarters, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Tachibana, Akira [Department of Biological Sciences, College of Science, Ibaraki University, Bunkyo 2-1-1, Mito, Ibaraki 310-8512 (Japan); and others

2015-09-15

Highlights: • T-cell lymphoma incidence, latency and weight did not change with age at exposure. • Lymphomas had frequent loss of heterozygosity on chromosomes 4, 11 and 19. • These lesions targeted the Cdkn2a, Ikaros and Pten tumor suppressor genes. • Age at exposure may influence which tumor suppressor genes are lost in each tumor. • The mechanisms of tumor suppressor gene loss were different at each locus. - Abstract: Children are considered more sensitive to radiation-induced cancer than adults, yet any differences in genomic alterations associated with age-at-exposure and their underlying mechanisms remain unclear. We assessed genome-wide DNA copy number and mutation of key tumor suppressor genes in T-cell lymphomas arising after weekly irradiation of female B6C3F1 mice with 1.2 Gy X-rays for 4 consecutive weeks starting during infancy (1 week old), adolescence (4 weeks old) or as young adults (8 weeks old). Although T-cell lymphoma incidence was similar, loss of heterozygosity at Cdkn2a on chromosome 4 and at Ikaros on chromosome 11 was more frequent in the two older groups, while loss at the Pten locus on chromosome 19 was more frequent in the infant-irradiated group. Cdkn2a and Ikaros mutation/loss was a common feature of the young adult-irradiation group, with Ikaros frequently (50%) incurring multiple independent hits (including deletions and mutations) or suffering a single hit predicted to result in a dominant negative protein (such as those lacking exon 4, an isoform we have designated Ik12, which lacks two DNA binding zinc-finger domains). Conversely, Pten mutations were more frequent after early irradiation (60%) than after young adult-irradiation (30%). Homozygous Pten mutations occurred without DNA copy number change after irradiation starting in infancy, suggesting duplication of the mutated allele by chromosome mis-segregation or mitotic recombination. Our findings demonstrate that while deletions on chromosomes 4 and 11 affecting Cdkn2

Radiation Therapy for Primary Cutaneous Anaplastic Large Cell Lymphoma: An International Lymphoma Radiation Oncology Group Multi-institutional Experience

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Million, Lynn, E-mail: lmillion@stanford.edu [Stanford Cancer Institute, Stanford, California (United States); Yi, Esther J.; Wu, Frank; Von Eyben, Rie [Stanford Cancer Institute, Stanford, California (United States); Campbell, Belinda A. [Department of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia); Dabaja, Bouthaina [The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Tsang, Richard W. [Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Ng, Andrea [Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Wilson, Lynn D. [Department of Therapeutic Radiology/Radiation Oncology, Yale School of Medicine, Yale Cancer Center, New Haven, Connecticut (United States); Ricardi, Umberto [Department of Oncology, University of Turin, Turin (Italy); Kirova, Youlia [Institut Curie, Paris (France); Hoppe, Richard T. [Stanford Cancer Institute, Stanford, California (United States)

2016-08-01

Purpose: To collect response rates of primary cutaneous anaplastic large cell lymphoma, a rare cutaneous T-cell lymphoma, to radiation therapy (RT), and to determine potential prognostic factors predictive of outcome. Methods and Materials: The study was a retrospective analysis of patients with primary cutaneous anaplastic large cell lymphoma who received RT as primary therapy or after surgical excision. Data collected include initial stage of disease, RT modality (electron/photon), total dose, fractionation, response to treatment, and local recurrence. Radiation therapy was delivered at 8 participating International Lymphoma Radiation Oncology Group institutions worldwide. Results: Fifty-six patients met the eligibility criteria, and 63 tumors were treated: head and neck (27%), trunk (14%), upper extremities (27%), and lower extremities (32%). Median tumor size was 2.25 cm (range, 0.6-12 cm). T classification included T1, 40 patients (71%); T2, 12 patients (21%); and T3, 4 patients (7%). The median radiation dose was 35 Gy (range, 6-45 Gy). Complete clinical response (CCR) was achieved in 60 of 63 tumors (95%) and partial response in 3 tumors (5%). After CCR, 1 tumor recurred locally (1.7%) after 36 Gy and 7 months after RT. This was the only patient to die of disease. Conclusions: Primary cutaneous anaplastic large cell lymphoma is a rare, indolent cutaneous lymphoma with a low death rate. This analysis, which was restricted to patients selected for treatment with radiation, indicates that achieving CCR was independent of radiation dose. Because there were too few failures (<2%) for statistical analysis on dose response, 30 Gy seems to be adequate for local control, and even lower doses may suffice.

Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial)

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2018-05-15

Advanced Malignant Solid Neoplasm; RB1 Positive; Recurrent Childhood Ependymoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Kidney Wilms Tumor; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Glioma; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdoid Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Refractory Ependymoma; Refractory Ewing Sarcoma; Refractory Glioma; Refractory Hepatoblastoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Glioma; Refractory Medulloblastoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Rhabdoid Tumor; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma

Can metabolic tumor parameters on primary staging 18F-FDG PET/CT aid in risk stratification of primary central nervous system lymphomas for patient management as a prognostic model?

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Okuyucu, K; Alagoz, E; Ince, S; Ozaydin, S; Arslan, N

Primary central nervous system (CNS) lymphoma is an aggressive and fatal extranodal non-Hodgkin lymphoma jailed in CNS at initial diagnosis. Its prognosis is poor and the disease has a fatal outcome when compared with systemic non-Hodgkin lymphoma. A few baseline risk stratification scoring systems have been suggested to estimate the prognosis mainly based on serum lactate dehydrogenase level,age, Karnofsky performance score, involvement of deep brain structures and cerebrospinal fluid protein concentration. 18 F-FDG PET/CT has a high prognostic value with respect to overall survival and disease-free survival in many cancers and lymphomas. We aimed to investigate metabolic tumor indexes on primary staging 18 F-FDG PET/CT as prognostic markers in primary CNS lymphoma. Fourteen patients with primary CNS diffuse large B-cell lymphoma (stage i) were enrolled in this retrospective cohort study. Primary staging 18 F-FDG PET/CT was performed and quantitative parameters like maximum standardized uptake value, average standardized uptake value, metabolic tumor volume and total lesion glycolysis (TLG) were calculated for all patients before the treatment. Cox regression models were performed to determine their relation with survival time. In the evaluation of all potential risk factors impacting recurrence/metastases (age, sex, serum lactate dehydrogenase, involvement of deep brain structures, maximum standardized uptake value, average standardized uptake value, metabolic tumor volume, and TLG) with univariate analysis, TLG remained statistically significant (P=.02). Metabolic tumor parameters are useful in prognosis estimation of primary CNS lymphomas, especially TLG, which is the most important one and may play a role in patient management. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Helicobacter pylori and Gastric Mucosa-associated Lymphoid Tissue (MALT) Lymphoma: Updated Review of Clinical Outcomes and the Molecular Pathogenesis.

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Suzuki, Hidekazu; Saito, Yoshimasa; Hibi, Toshifumi

2009-06-01

In most H. pylori-positive patients, gastric low-grade mucosa-associated lymphoid tissue (MALT) lymphomas regress both endoscopically and histopathologically after H. pylori eradication, but no factors that can be predictive of the response to the eradication have been definitively identified, and there is little information on how to determine the optimal observation period before additional treatment can be started. Here, clinical studies dealing with the diagnosis and treatment of gastric MALT lymphomas and H. pylori published during the last 5 years were systematically reviewed, and studies identifying the molecular approaches involved in the pathogenesis were summarized. Most of the clinical studies indicate a favorable effect of H. pylori eradication on the clinical outcome of gastric MALT lymphomas. Some studies suggest the necessity of additional treatment in nonresponders to H. pylori eradication, while others suggest the adoption of a watch-and-wait strategy. The molecular characteristics of MALT lymphomas could play an important role in prognostic prediction and the selection of further therapeutic intervention after the eradication. This updated review of gastric MALT lymphomas illustrates the potential efficacy of H. pylori eradication in tumor remission, but further molecular characterization is necessary to establish the most suitable therapeutic strategy for patients who do not respond to eradication.

[Post-therapeutic evolution and prognostic factors of intestinal lymphomas, Retrospective analysis of 42 cases].

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Sánchez-Fayos, M P; Hernández Guío, C; Rivas, M C; Outeiriño, J; González-Campos, C; Lobo, F

1993-12-01

To evaluate in retrospect the response to therapy and long-term evolution of a series of primitive intestinal lymphomas. The series was comprised of 42 patients diagnosed in our hospital during 1960-1962. The mean age was 34.5 years (range, 3-73), the M/F ratio was 21/21, and the histopathology distributes as follows: high grade (HG), 24 cases, low grade (LG), 12 cases, and mixed (LG/HG), 6 cases. B/T immunophenotype: 40/2. Staging: IE1,29 cases, IIE2-IV, 11 cases. The treatment applied in the series was classified in various types: ample surgical resection (aSR), 21 cases; partial surgical resection (pSR), 9 cases; abdominal radiation therapy (RT), 7 cases; monochemotherapy (MCT), 7 cases, and polychemotherapy (PCT), 28 cases. The correlation of clinicobiological variables with immediate response to treatment was evaluated by means of the chi square test, and the acturial post-therapeutic survival curves in accordance to the life tables, differences being calculated by the log rank test. Small intestine was the commonest site of involvement, 31 cases; ileocecal region, 7 cases; colon, 2 cases, and colon plus small intestine, 2 cases. Regardless of therapy type, complete remission (CR) was attained in 20 patients (47.5%), partial remission in 5; 11 cases were unresponsive (26.5%) and early death occurred in 6 instances (14.2%). The acturial post-therapeutic survival offered an 8-year expectancy of 47%. The correlation between immediate complete response and 16 clinico-biologic variables showed favourable significance for tumoral proliferation index (i.e., Pc10-positive cells studies. 2) Female sex, type of therapy, multifocal involvement, the need of emergency surgery and high LDH levels have significant value in univariate analyses.

Effect of recombinant adenovirus encoding human p53 tumor suppressor gene combined with radiation therapy on human lymphoma cells lines

International Nuclear Information System (INIS)

Yu Zeyang; Fan Wo; Li Dongqing; Zhu Ran; Wan Jianmei; Wang Yongqing; Wu Jinchang

2008-01-01

This paper analyzes the inhibitory effect and radiation sensitization of recombinant adenovirus encoding human p53 tumor suppressor gene (rAd-p53) on human lymphoma cell lines. Human lymphoma cell lines were treated with rAd-p53, radiation therapy and combined treatment, respectively. The cell growth inhibition was assessed by MTF. The cell cycle and apoptosis were detected by flow cytometry, and the p53 protein expression was detected by Western blotting. The results showed that extrinsic p53 gene have expressed to some degree, but not at high level. The role of inhibition and radiation sensitivity of rAd-p53 was not significant to human lymphoma cell lines. (authors)

Primary intracranial malignant lymphoma

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Matsumoto, Mikiro; Ohtsuka, Takatsugu; Kuroki, Takao; Shibata, Iekado; Terao, Hideo; Kudo, Motoshige

1988-01-01

Nine cases of primary intracranial malignant lymphoma, which accounts for 3.3 % of all intracranial tumors seen in the authors' institution, were studied in terms of diagnostic computed tomographic (CT) features, the tumors' histologic appearance, treatment, post-treatment blood immunologic and cerebrospinal fluid (CSF) characteristics, and outcome. The patients were seven males and two females aged 42 to 67 years. Their chief signs and symptoms on admission were intracranial hypertension, focal signs, and disturbance of consciousness. CT, which proved the most useful preoperative diagnostic technique, demonstrated multiple lesions in seven cases and, in all cases, regions of isodensity or slight high density that were enhanced by contrast medium. According to the patterns of enhancement, the tumors were classed as diffuse (three cases) or nodular (six cases). The former is considered typical of malignant lymphoma, whereas the latter type was sometimes indistinguishable from metastatic tumor and meningioma. At surgery, one patient underwent radical tumor excision, two partial removal, and six biopsy only. Histologic examination revealed one tumor to be of the diffuse small cell type, three of the medium cell type, and five of the large cell type (Lymphoma Study Group classification). Of seven tumors in which lymphocytes were examined by peroxidase-antiperoxidase staining, four were of the B cell type. Postoperatively, whole brain irradiation with 29 to 46 Gy was followed by local irradiation with 15 to 50 Gy. If the tumor persisted, one of three chemotherapies was administered. In one case, methotrexate was given intrathecally. Seven patients were divided into two groups: long remission (three) and recurrence (four). These two groups were compared in terms of serum immunoglobulin levels, T and B cell ratios, CSF characteristics, CT features, tumor cell type, and treatment. No clear differences were found. (author)

Primary multifocal osseous lymphoma in a child

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Sato, Takashi S.P. [University of Iowa, Carver College of Medicine, Iowa City, IA (United States); Ferguson, Polly J. [University of Iowa, Department of Pediatrics, Iowa City, IA (United States); Khanna, Geetika [Washington University, Mallinckrodt Institute of Radiology, St Louis, MO (United States)

2008-12-15

We report a case of primary multifocal osseous lymphoma in a 6-year-old girl presenting with multifocal osteolytic lesions without systemic symptoms or identifiable non-osseous primary tumor. The differential diagnoses for such a presentation include histiocytosis X, chronic recurrent multifocal osteomyelitis, acute lymphoblastic leukemia, metastatic disease, and primary bone lymphoma. Although non-Hodgkin lymphoma is common in the pediatric population, its presentation as a primary bone tumor, especially with multifocal disease, is extremely rare and is frequently misdiagnosed. We hope that awareness of this entity will help radiologists achieve timely diagnosis and intervention. (orig.)

Radiotherapy for mediastinal non-Hodgkin's lymphoma in children

International Nuclear Information System (INIS)

Masaki, Hidekazu

1985-01-01

Mediastinal non-Hodgkin's lymphoma in children is known to have an adverse prognosis, that is called ''lymphoblatic lymphoma''. Recently, chemotherapy for leukemia using multiple agents has been applied for non-Hodgkin's lymphoma in children, and this has improved relapse-free survival. Radiotherapy has been employed in order to reduce local recurrence. Two children received whole thoracic irradiation (10 Gy) who had mediastinal mass with malignant pleural effusion, then control of the effusion was achieved. Thereafter, radiation field was decreased in size to mantle field, and main tumor was treated to 30 Gy. In the course of treatment, mediastinal tumor was disappeared. Thereafter, radiation field was decreased in size to mantle field, and main tumor was treated to 30 Gy. In the course of treatment, mediastinal tumor was disappeared. For one child with only a mediastinal mass, mantle field was employed. He was treated to 30 Gy with chemotherapy. but he had CNS relapse. CNS prophylaxis is of considerable importance in this lymphoma according to the protocol of leukemia. (author)

The Impact of Drug Metabolism Gene Polymorphisms on Therapeutic Response and Survival in Diffuse Large B-Cell Lymphoma Patients.

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Pál, Ildikó; Illés, Árpád; Gergely, Lajos; Pál, Tibor; Radnay, Zita; Szekanecz, Zoltán; Zilahi, Erika; Váróczy, László

2018-04-01

Diffuse large B-cell lymphoma (DLBCL) accounts for 30% of all non-Hodgkin lymphomas (NHL) and 80% of agressive lymphomas. Besides the traditional International Prognostic Index (IPI), some other factors may also influence the prognosis of DLBCL patients. To study how the genetic polymorphisms in the metabolic pathway influence the event-free and overall survivals and therapeutic responses in DLBCL. The study was comprised of 51 patients (32 men, 19 women). The average age was 53.1 years. DLBCL was diagnosed between 2011 and 2016 and the average follow-up time was 3.78 years. These patients received 1-8 cycles (an average of 6.2 cycles) of rituximab, cyclophosphamide, doxorubicin, vincristin, prednisolon (R-CHOP) immunochemotherapy. Real-time polymerase chain reaction was used to determine the genetic polymorphisms of CYP2E1, GSTP1, NAT1, and NAT2 genes. Our results showed that the polymorphisms of CYP2E1, GSTP1, and NAT1 genes did not influence the prognosis of DLBCL patients significantly. In terms of the NAT2 gene, GG homozygous patients showed slightly better therapeutic response and survival results compared to those bearing an A allele; however, the differences were not statistically significant. Our results could not confirm that genetic polymorphism in metabolic pathways has any predictive role in DLBCL.

IMMUNOTHERAPY FOR EPSTEIN-BARR VIRUS-RELATED LYMPHOMAS

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Alana Kennedy-Nasser

2009-11-01

Full Text Available Latent EBV infection is associated with several malignancies, including EBV post-transplant lymphoproliferative disorders (LPD, Hodgkin and non-Hodgkin lymphomas, nasopharyngeal carcinoma and Burkitt lymphoma. The range of expression of latent EBV antigens varies in these tumors, which influences how susceptible the tumors are to immunotherapeutic approaches. Tumors expressing type III latency, such as in LPD, express the widest array of EBV antigens making them the most susceptible to immunotherapy. Treatment strategies for EBV-related tumors include restoring normal cellular immunity by adoptive immunotherapy with EBV-specific T cells and targeting the malignant B cells with monoclonal antibodies. We review the current immunotherapies and future studies aimed at targeting EBV antigen expression in these tumors.

Tumor Microenvironment Gene Signature as a Prognostic Classifier and Therapeutic Target

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2016-06-01

AWARD NUMBER: W81XWH-14-1-0107 TITLE: Tumor Microenvironment Gene Signature as a Prognostic Classifier and Therapeutic Target PRINCIPAL...AND SUBTITLE Tumor Microenvironment Gene Signature as a 5a. CONTRACT NUMBER W81XWH-14-1-0107 Prognostic Classifier and Therapeutic Target 5b...gene signature that correlates with poor survival in ovarian cancer patients. We are refining this gene signature to develop biomarkers for the

Primary Lymphoma of the Thyroid: Diagnostic and Therapeutic Considerations

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Basro Sarinah

2010-01-01

Conclusion: The diagnosis of primary thyroid lymphoma should be considered when dealing with rapidly growing goitres. The role of FNAC in diagnosing thyroid lymphoma is limited but it is still useful in the initial work-up. Nevertheless, surgical intervention is often required to establish the diagnosis and relieve critical airway compression. A combination of chemotherapy and irradiation is the mainstay of management.

Bovine lactoferricin induces caspase-independent apoptosis in human B-lymphoma cells and extends the survival of immune-deficient mice bearing B-lymphoma xenografts.

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Furlong, Suzanne J; Mader, Jamie S; Hoskin, David W

2010-06-01

Although current treatments based on the use of B-cell-specific anti-CD20 monoclonal antibodies and aggressive combinatorial chemotherapy have improved the survival of patients suffering from B-cell non-Hodgkin's lymphoma (NHL), some individuals fail to respond to treatment and relapses remain common. New and more effective treatments for B-cell NHL are therefore required. Bovine lactoferricin (LfcinB) is a cationic antimicrobial peptide that is cytotoxic for several human tumor cell lines but does not harm healthy cells. Here we show that in vitro treatment with LfcinB caused Raji and Ramos human B-lymphoma cells to die by apoptosis, as indicated by DNA fragmentation, chromatin condensation, and nuclear disintegration. LfcinB killed B-lymphoma cells more efficiently at low serum concentrations and was inhibited in the presence of exogenous bovine serum albumin, suggesting partial neutralization of cationic LfcinB by anionic serum components. LfcinB-induced apoptosis in B-lymphoma cells was caspase-independent since caspase-3 activation was not detected by Western blotting and the general caspase inhibitor z-VAD-fmk did not prevent LfcinB-induced DNA fragmentation. Importantly, immune-deficient SCID/beige mice that were inoculated intravenously with Ramos B-lymphoma cells in order to model B-cell NHL exhibited extended survival following systemic administration of LfcinB, indicating that LfcinB warrants further investigation as a novel therapeutic agent for the possible treatment of B-cell NHL. Copyright 2010 Elsevier Inc. All rights reserved.

Nasosinusal Lymphoma of T Natural Killer Cells: Case Report

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Castro, Victor Labres da Silva

2011-01-01

Full Text Available Introduction: The primary nasal lymphoma is an uncommon extranodal tumor and represents 0.44% of all Extranodal lymphomas in this region. The primary nasal lymphoma derives from the T-lineage in nearly 75% of the cases. Objective: To describe a case of nasosinusal lymphoma of T Natural Killer cells, attended in the Clinical Hospital of the Federal University of Goiás. Case Report: 48-year-old female patient with diffuse tumefaction in the left hemiface of firm-elastic consistency and painful upon digital compression. Face sinuses tomography identified a total maxillary veiling to the left and some posterior ethmoidal cells. With the diagnostic hypothesis of a tumor affection, we opted for the surgical removal via a transmaxillary approach and the material was sent for biopsy. The histopathological exam diagnosed a highly necrotic tumor of angiocentric pattern, polymorphic and atypical lymphoid population (T /NK Lymphoma; with the prognosis, the patient was submitted to chemical therapy with total regression of the facial edema. Final Comments: The otorhinolaryngologist must be attentive as regards the existence of lymphomas among the nasosinusal diseases, because the early diagnosis improves the survival as it prevents metastases, growth and local destruction.

Primary periosteal lymphoma: an unusual presentation of non-Hodgkin's lymphoma with radiographic, MR imaging, and pathologic correlation

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Campbell, Scot E.; Beall, Douglas P.; Sanders, Timothy G. [Department of Radiology, Wilford Hall Medical Center, 759th MDTS/MTRD, 2200 Bergquist Drive, Suite 1, Lackland AFB, TX 78236-5300 (United States); Filzen, Timothy W.; Parsons, Theodore W. [Department of Orthopedic Surgery, Wilford Hall Medical Center, 59th MDW/MCSO, 2200 Bergquist Drive, Suite 1, Lackland AFB, TX 78236-5300 (United States); Bezzant, Shane M. [Department of Radiology, Brooke Army Medical Center, 3851 Roger Brooke Drive, Bldg 3600, Fort Sam Houston, TX 78234-6200 (United States); Burton, Mark P. [Department of Pathology, Wilford Hall Medical Center, 59th MDW/MTLP, 2200 Bergquist Drive, Suite 1, Lackland AFB, TX 78236-5300 (United States)

2003-04-01

This report describes a primary periosteal location of non-Hodgkin's lymphoma, without nodal disease, and without adjacent intramedullary disease at presentation. The clinical and imaging appearance of periosteal lymphoma simulates other neoplastic osseous surface tumors more than that of lymphoma in other locations. Consideration of this rare presentation of non-Hodgkin's lymphoma in the differential diagnosis of periosteal bone lesions can be helpful to ensure proper diagnosis and treatment. (orig.)

Vitamin E - its status and role in leukemia and lymphoma

International Nuclear Information System (INIS)

Dasgupta, J.; Das, S.; Sanyal, U.

1993-01-01

A comparative study has been performed on the relationship between vitamin E and immuno-function in normal and malignant condition in human and murine systems. Further, the effects of supplemental vitamin E on tumor take, host survival and tumor growth has been studied in a transplantable lymphoma in mice. Vitamin E was assayed in serum samples from normal subjects and from patient with leukemia and lymphoma by high performance liquid chromatography (HPLC) The murine group included Dalton's ascite lymphoma (DL), Schwartz lymphoblastic leukemia (SVL) and Moloney lymphoblastic leukemia (MVL). Serum vitamin E was found to be lower than that of the normal controls in all cases of leukemia and lymphoma both in human and lymphoma. Supplementary vitamin E administered at the initial phase of development of murine lymphomas reduced the rate of tumor growth, improved host survival and elevated serum vitamin E level. Vitamin E supplementation also activated specific induced blastogenesis of peripheral blood lymphocytes (PBL) and elevated serum IgG level. IgM remained unaltered and and macrophage activity did not seem to be affected. The present findings indicated a low status of vitamin E in tumor bearing host and beneficial effect of supplemental vitamin E on the host which was mediated by the host immune system. (author)

Open-Label, Multicenter, Phase 1/2 Study of Tazemetostat (EZH2 Histone Methyl Transferase [HMT] Inhibitor) as a Single Agent in Subjects With Adv. Solid Tumors or With B-cell Lymphomas and Tazemetostat in Combination With Prednisolone in Subjects With DLBCL

Science.gov (United States)

2018-04-12

B-cell Lymphomas (Phase 1); Advanced Solid Tumors (Phase 1); Diffuse Large B-cell Lymphoma (Phase 2); Follicular Lymphoma (Phase 2); Transformed Follicular Lymphoma; Primary Mediastinal Large B-Cell Lymphoma

Targeted Delivery of siRNA Therapeutics to Malignant Tumors

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Qixin Leng

2017-01-01

Full Text Available Over the past 20 years, a diverse group of ligands targeting surface biomarkers or receptors has been identified with several investigated to target siRNA to tumors. Many approaches to developing tumor-homing peptides, RNA and DNA aptamers, and single-chain variable fragment antibodies by using phage display, in vitro evolution, and recombinant antibody methods could not have been imagined by researchers in the 1980s. Despite these many scientific advances, there is no reason to expect that the ligand field will not continue to evolve. From development of ligands based on novel or existing biomarkers to linking ligands to drugs and gene and antisense delivery systems, several fields have coalesced to facilitate ligand-directed siRNA therapeutics. In this review, we discuss the major categories of ligand-targeted siRNA therapeutics for tumors, as well as the different strategies to identify new ligands.

Double-hit lymphomas constitute a highly aggressive subgroup in diffuse large B-cell lymphomas in the era of rituximab.

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Kobayashi, Tsutomu; Tsutsumi, Yasuhiko; Sakamoto, Natsumi; Nagoshi, Hisao; Yamamoto-Sugitani, Mio; Shimura, Yuji; Mizutani, Shinsuke; Matsumoto, Yosuke; Nishida, Kazuhiro; Horiike, Shigeo; Asano, Naoko; Nakamura, Shigeo; Kuroda, Junya; Taniwaki, Masafumi

2012-11-01

The incorporation of rituximab in immunochemotherapy has improved treatment outcomes for diffuse large B-cell lymphoma, but the prognosis for some diffuse large B-cell lymphomas remains dismal. Identification of adverse prognostic subgroups is essential for the choice of appropriate therapeutic strategy. We retrospectively investigated the impact of so-called 'double-hit' cytogenetic abnormalities, i.e. cytogenetic abnormalities involving c-MYC co-existing with other poor prognostic cytogenetic abnormalities involving BCL2, BCL6 or BACH2, on treatment outcomes for 93 consecutive diffuse large B-cell lymphoma patients. According to the revised international prognostic index, no patients were cytogenetically diagnosed with double-hit lymphomas in the 'very good' risk group or in the 'good' risk group, while 5 of 33 patients had double-hit lymphomas in the 'poor' risk group. All the double-hit lymphoma patients possessed both nodal and extranodal involvement. The overall complete response rate was 89.3%, overall survival 87.1% and progression-free survival 75.8% over 2 years (median observation period: 644 days). The complete response rates were 93.2% for the non-double-hit lymphoma patients and 40.0% for the double-hit lymphoma patients. Significantly longer progression-free survival and overall survival were observed for the 'very good' and the 'good' risk patients than for the 'poor' risk patients. Moreover, the progression-free survival of double-hit lymphoma was significantly shorter than that of the non-double-hit lymphoma 'poor' risk patients (P = 0.016). In addition, the overall survival of the double-hit lymphoma patients also tended to be shorter than that of the non-double-hit lymphoma 'poor' risk group. The diagnosis of double-hit lymphoma can help discriminate a subgroup of highly aggressive diffuse large B-cell lymphomas and indicate the need for the development of novel therapeutic strategies for double-hit lymphoma.

Cell mediated therapeutics for cancer treatment: Tumor homing cells as therapeutic delivery vehicles

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Balivada, Sivasai

Many cell types were known to have migratory properties towards tumors and different research groups have shown reliable results regarding cells as delivery vehicles of therapeutics for targeted cancer treatment. Present report discusses proof of concept for 1. Cell mediated delivery of Magnetic nanoparticles (MNPs) and targeted Magnetic hyperthermia (MHT) as a cancer treatment by using in vivo mouse cancer models, 2. Cells surface engineering with chimeric proteins for targeted cancer treatment by using in vitro models. 1. Tumor homing cells can carry MNPs specifically to the tumor site and tumor burden will decrease after alternating magnetic field (AMF) exposure. To test this hypothesis, first we loaded Fe/Fe3O4 bi-magnetic NPs into neural progenitor cells (NPCs), which were previously shown to migrate towards melanoma tumors. We observed that NPCs loaded with MNPs travel to subcutaneous melanoma tumors. After alternating magnetic field (AMF) exposure, the targeted delivery of MNPs by the NPCs resulted in a mild decrease in tumor size (Chapter-2). Monocytes/macrophages (Mo/Ma) are known to infiltrate tumor sites, and also have phagocytic activity which can increase their uptake of MNPs. To test Mo/Ma-mediated MHT we transplanted Mo/Ma loaded with MNPs into a mouse model of pancreatic peritoneal carcinomatosis. We observed that MNP-loaded Mo/Ma infiltrated pancreatic tumors and, after AMF treatment, significantly prolonged the lives of mice bearing disseminated intraperitoneal pancreatic tumors (Chapter-3). 2. Targeted cancer treatment could be achieved by engineering tumor homing cell surfaces with tumor proteases cleavable, cancer cell specific recombinant therapeutic proteins. To test this, Urokinase and Calpain (tumor specific proteases) cleavable; prostate cancer cell (CaP) specific (CaP1 targeting peptide); apoptosis inducible (Caspase3 V266ED3)- rCasp3V266ED3 chimeric protein was designed in silico. Hypothesized membrane anchored chimeric protein (rCasp3V

Lymphoma cytogenetics.

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Dave, Bhavana J; Nelson, Marilu; Sanger, Warren G

2011-12-01

Lymphomas are a heterogeneous group of neoplasms with distinct morphologic, immunologic, and cytogenetic characteristics. Overlapping morphologic and immunophenotypic features often makes accurate diagnosis difficult. Cytogenetics helps simplify the diagnostic complexities presented in transforming and progressive lymphoid malignancies. Genetic studies using technical advances such as fluorescence in situ hybridization and the newer approaches of array comparative genomic hybridization and gene expression profiling play a critical and often defining role in the diagnosis, progression, prognosis, and therapeutic stratification. This article reviews characteristic cytogenetic abnormalities in specific subtypes of lymphomas at diagnosis, disease progression, and prognosis.

Antibody therapies for lymphoma in children

NARCIS (Netherlands)

de Zwart, Verena; Gouw, Samantha C.; Meyer-Wentrup, Friederike A. G.

2016-01-01

Lymphomas are the third most common malignancy in childhood. Cure rates are high but have reached a plateau. Therefore new treatment modalities should be developed. Antibody therapy is a successful new treatment option in adult lymphoma. However, none of the therapeutic antibodies available for

Immunohistochemical prognostic indicators of lymphoma tumors

African Journals Online (AJOL)

STORAGESEVER

2009-10-05

Oct 5, 2009 ... Lymphoma tissues were obtained from 50 patients (Royal Medical Services 1990 - 1996), which were ... wide range of cellular stresses including hypoxia, heat shock ... modulating DNA repair, replication and recombination.

Effect of Bcl11b genotypes and γ-radiation on the development of mouse thymic lymphomas

International Nuclear Information System (INIS)

Yoshikai, Yoshihiro; Sato, Toshihiro; Morita, Shinichi; Kohara, Yuki; Takagi, Ritsuo; Mishima, Yukio; Kominami, Ryo

2008-01-01

Bcl11b is a haploinsufficient tumor suppressor gene and expressed in many tissues such as thymus, brain and skin. Irradiated Bcl11b +/- heterozygous mice mostly develop thymic lymphomas, but the preference of Bcl11b inactivation for thymic lymphomas remains to be addressed. We produced Bcl11b +/- heterozygous and Bcl11b wild-type mice of p53 +/- background and compared their incidence of γ-ray induced thymic lymphomas. Majority of the tumors in p53 +/- mice were skin tumors, and only 5 (36%) of the 14 tumors were thymic lymphomas. In contrast, Bcl11b +/- p53 +/- doubly heterozygous mice developed thymic lymphomas at the frequency of 27 (79%) of the 34 tumors developed (P = 0.008). This indicates the preference of Bcl11b impairment for thymic lymphoma development. We also analyzed loss of the wild-type alleles in the 27 lymphomas, a predicted consequence given by γ-irradiation. However, the loss frequency was low, only six (22%) for Bcl11b and five (19%) for p53. The frequencies did not differ from those of spontaneously developed thymic lymphomas in the doubly heterozygous mice, though the latency of lymphoma development markedly differed between them. This suggests that the main contribution of irradiation at least in those mice is not for the tumor initiation by inducing allelic losses but probably for the promotion of thymic lymphoma development

PET imaging in pediatric Hodgkin's lymphoma

International Nuclear Information System (INIS)

Hudson, M.M.; Krasin, M.J.; Kaste, S.C.

2004-01-01

Advances in diagnostic imaging technology, especially functional imaging modalities like positron emission tomography (PET), have significantly influenced the staging and treatment approaches used for pediatric Hodgkin's lymphoma. Today, the majority of children and adolescents diagnosed with Hodgkin's lymphoma will be cured following treatment with noncross-resistant combination chemotherapy alone or in combination with low-dose, involved-field radiation. This success produced a greater appreciation of long-term complications related to radiation, chemotherapy, and surgical staging that prompted significant changes in staging and treatment protocols for children and adolescents with Hodgkin's lymphoma. Contemporary treatment for pediatric Hodgkin's lymphoma uses a risk-adapted approach that reduces the number of combination chemotherapy cycles and radiation treatment fields and doses for patients with localized favorable disease presentation. Advances in diagnostic imaging technology have played a critical role in the development of these risk-adapted treatment regimens. The introduction of computed tomography (CT) provided an accurate and non-invasive modality to define nodal involvement below the diaphragm that motivated the change from surgical to clinical staging. The introduction of functional imaging modalities, like positron emission tomography (PET) scanning, provided the means to correlate tumor activity with anatomic features generated by CT and modify treatment based on tumor response. For centers with access to this modality, PET imaging plays an important role in staging, evaluating tumor response, planning radiation treatment fields, and monitoring after completion of therapy for pediatric Hodgkin's lymphoma. (orig.)

IL-15 deficient tax mice reveal a role for IL-1α in tumor immunity.

Directory of Open Access Journals (Sweden)

Daniel A Rauch

Full Text Available IL-15 is recognized as a promising candidate for tumor immunotherapy and has been described as both a promoter of cancer and a promoter of anti-cancer immunity. IL-15 was discovered in cells transformed by HTLV-1, the etiologic agent of adult T cell leukemia/lymphoma (ATL and the human retrovirus that carries the Tax oncogene. We have developed the TAX-LUC mouse model of ATL in which Tax expression drives both malignant transformation and luciferase expression, enabling non-invasive imaging of tumorigenesis in real time. To identify the role of IL-15 in spontaneous development of lymphoma in vivo, an IL-15(-/- TAX-LUC strain was developed and examined. The absence of IL-15 resulted in aggressive tumor growth and accelerated mortality and demonstrated that IL-15 was not required for Tax-mediated lymphoma but was essential for anti-tumor immunity. Further analysis revealed a unique transcriptional profile in tumor cells that arise in the absence of IL-15 that included a significant increase in the expression of IL-1α and IL-1α-regulated cytokines. Moreover, anti-IL-1α antibodies and an IL-1 receptor antagonist (Anakinra were used to interrogate the potential of IL-1α targeted therapies in this model. Taken together, these findings identify IL-15 and IL-1α as therapeutic targets in lymphoma.

Single-mass mutations associated with mouse lymphomas

International Nuclear Information System (INIS)

Guerrero, I.; Berman, J.W.; Diamond, L.E.; Newcomb, E.W.; Villasante, A.

1986-01-01

The authors study the induction of mouse lymphomas after treatment with a chemical carcinogen, nitrosomethyl urea (NMU), or with gamma irradiation. The koplan fractionated gamma radiation scheme and an established protocol for NMU tumor formation were chosen as protocols for induction of mouse lymphomas. In both cases, the mice developed thymic lymphomas with up to 90% incidence. In NMU induction, the latency period is shorter than irradiation

Tumor angiogenesis--a new therapeutic target in gliomas

DEFF Research Database (Denmark)

Lund, E L; Spang-Thomsen, M; Skovgaard-Poulsen, H

1998-01-01

significant angiogenic activity primarily by the expression of the angiogenic factor VEGF Anti-angiogenic therapy represents a new promising therapeutic modality in solid tumors. Several agents are currently under evaluation in clinical trials. The present review describes the principal inducers...

Therapeutic limitations in tumor-specific CD8+ memory T cell engraftment

International Nuclear Information System (INIS)

Bathe, Oliver F; Dalyot-Herman, Nava; Malek, Thomas R

2003-01-01

Adoptive immunotherapy with cytotoxic T lymphocytes (CTL) represents an alternative approach to treating solid tumors. Ideally, this would confer long-term protection against tumor. We previously demonstrated that in vitro-generated tumor-specific CTL from the ovalbumin (OVA)-specific OT-I T cell receptor transgenic mouse persisted long after adoptive transfer as memory T cells. When recipient mice were challenged with the OVA-expressing E.G7 thymoma, tumor growth was delayed and sometimes prevented. The reasons for therapeutic failures were not clear. OT-I CTL were adoptively transferred to C57BL/6 mice 21 – 28 days prior to tumor challenge. At this time, the donor cells had the phenotypical and functional characteristics of memory CD8+ T cells. Recipients which developed tumor despite adoptive immunotherapy were analyzed to evaluate the reason(s) for therapeutic failure. Dose-response studies demonstrated that the degree of tumor protection was directly proportional to the number of OT-I CTL adoptively transferred. At a low dose of OT-I CTL, therapeutic failure was attributed to insufficient numbers of OT-I T cells that persisted in vivo, rather than mechanisms that actively suppressed or anergized the OT-I T cells. In recipients of high numbers of OT-I CTL, the E.G7 tumor that developed was shown to be resistant to fresh OT-I CTL when examined ex vivo. Furthermore, these same tumor cells no longer secreted a detectable level of OVA. In this case, resistance to immunotherapy was secondary to selection of clones of E.G7 that expressed a lower level of tumor antigen. Memory engraftment with tumor-specific CTL provides long-term protection against tumor. However, there are several limitations to this immunotherapeutic strategy, especially when targeting a single antigen. This study illustrates the importance of administering large numbers of effectors to engraft sufficiently efficacious immunologic memory. It also demonstrates the importance of targeting several

Use of magnetic resonance imaging to detect neoplastic meningitis: Limited use in leukemia and lymphoma but convincing results in solid tumors

International Nuclear Information System (INIS)

Pauls, Sandra; Fischer, Ann-Cathrin; Brambs, Hans-Jürgen; Fetscher, Sebastian; Höche, Wolfram; Bommer, Martin

2012-01-01

Background: An early diagnosis of meningitis is important to improve patients’ survival. Data about a direct comparison of cerebrospinal fluid cytology (CSF-cytology) and MRI are very limited. Therefore, the aim of this study was to compare these two diagnostic modalities in diagnosing meningitis in patients with hematopoietic and solid malignancies. Methods: In 68 patients suspicious for neoplastic meningitis, cytology and MRI (1.5 T) was performed. The meningeal, pial or intraparenchymal hyperintense signal or contrast enhancement was correlated to the final CNS diagnosis and to cytology. Results: 44 patients (64.7%) had neoplastic meningitis, 21 patients (30.9%) had non-neoplastic meningitis. The sensitivity to diagnose meningeal disease was 49.2% for MRI and 95.4% for cytology (p < 0.001). In patients with neoplastic meningitis, sensitivity was 45.5% for MRI and 93.2% for cytology (p < 0.001). In patients with infectious meningitis, sensitivity was 57.1% for MRI and 100% for cytology (p = 0.0013). In patients with solid tumors, the sensitivity was 84.6% for both diagnostic methods. The sensitivity for MRI was low in patients with leukemia (20.0%) and lymphoma (37.5%). The positive predictive value (PPV) for MRI to differentiate infectious from neoplastic meningitis was high in patients with infectious meningitis (75.0%), in patients with lymphoma (83.3%), and in patients with solid tumors (72.7%). Ppv was low in patients with leukemia (33.3%). Conclusion: Diagnostic value of MRI for diagnosing meningitis is especially limited in patients with hematopoietic malignancies. MRI better detected leptomeningeal involvement caused by solid tumors than by leukemia or lymphoma. The ppv to specify neoplastic meningitis depends on tumor subtype.

Non-Hodgkin's lymphomas

International Nuclear Information System (INIS)

Glatstein, E.; Wasserman, T.H.

1987-01-01

Non-Hodgkin's lymphomas are a varied and complex group of diseases that must be distinguished from Hodgkin's disease. The latter almost always begins in lymph nodes and spreads primarily in an axial fashion; non-Hodgkin's lymphomas may begin either in lymph nodes or in extranodal tissue and can spread both in an axial fashion and centrifugally. Because of changes in pathology terminology and the introduction of a classification using cell surface markers, many prognostic groups of patients with lymphomas have evolved. Therapeutic choices and prognosis are greatly influenced by variations in anatomic sites and extent of disease. Currently, the decisions on management require a balancing of radiation therapy with systemic chemotherapy. In some cases, radiation therapy alone may be sufficient; however, because most patients with non-Hodgkins's lymphomas tend to have advanced disease, a large percentage of patients will be managed with chemotherapy alone or in combination with radiation therapy

Targeting interleukin-11 receptor in leukemia and lymphoma: A functional ligand-directed study and hematopathology analysis of patient-derived specimens

Science.gov (United States)

Karjalainen, Katja; Jaalouk, Diana E.; Bueso-Ramos, Carlos; Bover, Laura; Sun, Yan; Kuniyasu, Akihiko; Driessen, Wouter H. P.; Cardó-Vila, Marina; Rietz, Cecilia; Zurita, Amado J.; O’Brien, Susan; Kantarjian, Hagop M.; Cortes, Jorge E.; Calin, George A.; Koivunen, Erkki; Arap, Wadih; Pasqualini, Renata

2015-01-01

Purpose The interleukin-11 receptor (IL-11R) is an established molecular target in primary tumors of bone, such as osteosarcoma, and in secondary bone metastases from solid tumors such as prostate cancer. However, its potential role in management of hematopoietic malignancies has not yet been determined. Here we evaluated the IL-11R as a candidate therapeutic target in human leukemia and lymphoma. Experimental Design and Results First, we show that the IL-11R protein is expressed in a variety of human leukemia- and lymphoma derived cell lines and in a large panel of bone marrow samples from leukemia and lymphoma patients, while expression is absent from non-malignant control bone marrow. Moreover, a targeted peptidomimetic prototype (termed BMTP-11) specifically bound to leukemia and lymphoma cell membranes, induced ligand-receptor internalization mediated by the IL-11R, and resulted in a specific dose-dependent cell death induction in these cells. Finally, a pilot drug lead-optimization program yielded a new myristoylated BMTP-11 analog with an apparent improved anti-leukemia cell profile. Conclusion These results indicate (i) that the IL-11R is a suitable cell surface target for ligand-directed applications in human leukemia and lymphoma and (ii) that BMTP-11 and its derivatives have translational potential against this group of malignant diseases. PMID:25779950

Targeting IL11 Receptor in Leukemia and Lymphoma: A Functional Ligand-Directed Study and Hematopathology Analysis of Patient-Derived Specimens.

Science.gov (United States)

Karjalainen, Katja; Jaalouk, Diana E; Bueso-Ramos, Carlos; Bover, Laura; Sun, Yan; Kuniyasu, Akihiko; Driessen, Wouter H P; Cardó-Vila, Marina; Rietz, Cecilia; Zurita, Amado J; O'Brien, Susan; Kantarjian, Hagop M; Cortes, Jorge E; Calin, George A; Koivunen, Erkki; Arap, Wadih; Pasqualini, Renata

2015-07-01

The IL11 receptor (IL11R) is an established molecular target in primary tumors of bone, such as osteosarcoma, and in secondary bone metastases from solid tumors, such as prostate cancer. However, its potential role in management of hematopoietic malignancies has not yet been determined. Here, we evaluated the IL11R as a candidate therapeutic target in human leukemia and lymphoma. First, we show that the IL11R protein is expressed in a variety of human leukemia- and lymphoma-derived cell lines and in a large panel of bone marrow samples from leukemia and lymphoma patients, whereas expression is absent from nonmalignant control bone marrow. Moreover, a targeted peptidomimetic prototype (termed BMTP-11), specifically bound to leukemia and lymphoma cell membranes, induced ligand-receptor internalization mediated by the IL11R, and resulted in a specific dose-dependent cell death induction in these cells. Finally, a pilot drug lead-optimization program yielded a new myristoylated BMTP-11 analogue with an apparent improved antileukemia cell profile. These results indicate (i) that the IL11R is a suitable cell surface target for ligand-directed applications in human leukemia and lymphoma and (ii) that BMTP-11 and its derivatives have translational potential against this group of malignant diseases. ©2015 American Association for Cancer Research.

Primary pancreatic non-Hodgkin's lymphoma

Directory of Open Access Journals (Sweden)

Čolović Nataša

2005-01-01

Full Text Available Diffuse large-cell B lymphoma of the pancreas is a rare disease, representing less than 1% of all non-Hodgkin's lymphomas and less than 0.9% of all malignant tumors of the pancreas. About 150 cases of the disease have been observed so far. The tumors are more frequent in the head of the pancreas then in other parts of the organ. They are usually larger (average size of 8 cm and are non-resectionable. As a rule, exact diagnosis is based on the histology and the immunohistology of the specimen taken during open surgery performed for general diagnosis of the pancreatic tumor. Very rarely can a very reliable and experienced cytopathologist establish a proper diagnosis based on material obtained from a fine needle biopsy. The disease usually responds positively to immunochemotherapy according to protocol R-CHOP. Occasionally, additional radiotherapy may be required. We present two women, 66 and 49 years old, in whom a diagnosis of large-cell B lymphoma of the pancreas was established, based on the histology and the immunohistochemistry of a specimen taken during open surgery performed in order to remove pancreatic tumors, which turned out to be non-resectionable. After immunochemotherapy, the symptoms disappeared and the tumors shrank, in one patient after additional radiotherapy. The authors would like to point out the importance of a proper histological diagnosis, which permitted the application of immunochemotherapy alone or together with additional radiotherapy with at least temporarily favorable results.

Targeting personalized medicine in a non-Hodgkin lymphoma patient with {sup 18F}-FDG and {sup 18F}-choline PET/CT

Energy Technology Data Exchange (ETDEWEB)

Ribeiro, Thalles H.; Filho, Raul S.; Castro, Ana Carolina G.; Paulino Junior, Eduardo; Mamede, Marcelo, E-mail: mamede.mm@gmail.com [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil)

2017-02-15

Early diagnosis and staging of non-Hodgkin lymphoma (NHL) is essential for therapeutic strategy decision. Positron emission tomography/computed tomography (PET/CT) with fluorodeoxyglucose (FDG), a glucose analogue, labeled with fluor-18 ({sup 18F}-FDG) has been used to evaluate staging, therapy response and prognosis in NHL patients. However, in some cases, {sup 18F}-FDG has shown false- -positive uptake due to inflammatory reaction after chemo and/or radiation therapy. In this case report, we present a NHL patient evaluated with {sup 18F}-FDG and {sup 18F}-choline PET/CT scan imaging pre- and post-therapy. {sup 18F}-FDG and {sup 18F}-choline PET/CT were performed for the purpose of tumor staging and have shown intense uptake in infiltrative tissue as well as in the lymph node, but with some mismatching in the tumor. Post-treatment {sup 18F}-FDG and {sup 18F}-choline PET/ CT scans revealed no signs of radiotracer uptake, suggesting complete remission of the tumor. {sup 18F}-choline may be a complimentary tool for staging and assessment of therapeutic response in non-Hodgkin lymphoma, while non-{sup 18F}-FDG tracer can be used for targeted therapy and patient management. (author)

Synchronous meningioma and anaplastic large cell lymphoma.

Science.gov (United States)

Colen, Chaim B; Rayes, Mahmoud; Kupsky, William J; Guthikonda, Murali

2010-06-01

Synchronous primary brain tumors are exceedingly rare. When they occur, most cases are associated with metastatic disease. To the best of our knowledge, we report the first case of an atypical meningioma infiltrated by a T-cell-primary central nervous system lymphoma (PCNSL), specifically anaplastic large cell lymphoma (ALCL). We present a novel, unifying, plausible mechanism for its origin based on theories in the current literature. A 65-year-old man with a history of near-total resection of atypical meningioma presented with a complaint of progressive headaches. Imaging revealed recurrent tumor. Left frontal-temporal craniotomy with near-total tumor resection followed by radiation was performed. Recurrent symptomatic tumor led to repeat left frontotemporal craniotomy with tumor resection and partial anterior temporal lobectomy. Part of the specimen showed predominantly fibrotic neoplasm composed of nests and whorls of meningothelial cells, highlighted by epithelial membrane antigen (EMA) staining. The remainder of the specimen consisted of densely cellular neoplasm centered in connective tissue, including areas involved by meningioma. This tumor was composed of moderately large lymphoid cells with large nuclei, prominent nucleoli, and amphophilic cytoplasm. These cells were strongly immunoreactive for CD3 and CD30 but remained unstained with EMA, anaplastic lymphoma kinase-1 (ALK-1), CD15 or cytotoxic associated antigen TIA-1. Smaller mature lymphocytes, chiefly T-cells, were intermixed. The morphologic and immunohistochemical features were considered typical of anaplastic large T-cell lymphoma. The pathogenesis of this association may have been due to radiation-mediated breakdown of the blood-brain barrier with subsequent T-cell infiltration and proliferation. We advocate aggressive resection and long-term surveillance for individuals with metastasis, especially higher-grade neoplasms that receive radiotherapy.

Prognostic value of tumor necrosis at CT in diffuse large B-cell lymphoma

Energy Technology Data Exchange (ETDEWEB)

Adams, Hugo J.A., E-mail: h.j.a.adams@gmail.com [Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht (Netherlands); Klerk, John M.H. de [Department of Nuclear Medicine, Meander Medical Center, Amersfoort (Netherlands); Fijnheer, Rob [Department of Hematology, Meander Medical Center, Amersfoort (Netherlands); Dubois, Stefan V. [Department of Pathology, Meander Medical Center, Amersfoort (Netherlands); Nievelstein, Rutger A.J.; Kwee, Thomas C. [Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht (Netherlands)

2015-03-15

Highlights: •CT is compulsory for staging newly diagnosed DLBCL. •Approximately 13.7% of DLBCL patients have tumor necrosis at CT. •Tumor necrosis status at CT is not associated with any NCCN-IPI factor. •Patients with tumor necrosis at CT have a significantly worse outcome. -- Abstract: Objective: To determine the prognostic value of tumor necrosis at computed tomography (CT) in newly diagnosed diffuse large B-cell lymphoma (DLBCL). Materials and methods: This retrospective study included 51 patients with newly diagnosed DLBCL who had undergone both unenhanced and intravenous contrast-enhanced CT before R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin and prednisolone) chemo-immunotherapy. Presence of tumor necrosis was visually and quantitatively assessed at CT. Associations between tumor necrosis status at CT and the National Comprehensive Cancer Network (NCCN) International Prognostic Index (IPI) factors were assessed. Cox regression analysis was used to determine the prognostic impact of NCCN-IPI scores and tumor necrosis status at CT. Results: There were no correlations between tumor necrosis status at CT and the NCCN-IPI factors categorized age (ρ = −0.042, P = 0.765), categorized lactate dehydrogenase (LDH) ratio (ρ = 0.201, P = 0.156), extranodal disease in major organs (φ = −0.245, P = 0.083), Ann Arbor stage III/IV disease (φ = −0.208, P = 0.141), and Eastern Cooperative Oncology Group (ECOG) performance status (φ = 0.015, P = 0.914). In the multivariate Cox proportional hazards model, only tumor necrosis status at CT was an independent predictive factor of progression-free survival (P = 0.003) and overall survival (P = 0.004). Conclusion: The findings of this study indicate the prognostic potential of tumor necrosis at CT in newly diagnosed DLBCL.

Clinical aspects and therapy of non-Hodgkin lymphomas

International Nuclear Information System (INIS)

Meissner, K.; Jaenner, M.

1981-01-01

Definition, incidence and distribution of age and sex of cutaneous non-Hodgkin lymphomas are presented. Clinical appearance of cutaneous non-Hodgkin lymphomas may exhibit specific and unspecific cutaneous lesions. Histological examination is of greatest importance for subsequent diagnostic and therapeutic procedures. Topical treatment, X-ray- or photochemotherapy are performed in the early stages, in case of therapeutic resistance and in advanced disease systemical chemotherapy is indicated. (orig.) [de

Deregulated expression of HDAC9 in B cells promotes development of lymphoproliferative disease and lymphoma in mice

Directory of Open Access Journals (Sweden)

Veronica S. Gil

2016-12-01

Full Text Available Histone deacetylase 9 (HDAC9 is expressed in B cells, and its overexpression has been observed in B-lymphoproliferative disorders, including B-cell non-Hodgkin lymphoma (B-NHL. We examined HDAC9 protein expression and copy number alterations in primary B-NHL samples, identifying high HDAC9 expression among various lymphoma entities and HDAC9 copy number gains in 50% of diffuse large B-cell lymphoma (DLBCL. To study the role of HDAC9 in lymphomagenesis, we generated a genetically engineered mouse (GEM model that constitutively expressed an HDAC9 transgene throughout B-cell development under the control of the immunoglobulin heavy chain (IgH enhancer (Eμ. Here, we report that the Eμ-HDAC9 GEM model develops splenic marginal zone lymphoma and lymphoproliferative disease (LPD with progression towards aggressive DLBCL, with gene expression profiling supporting a germinal center cell origin, as is also seen in human B-NHL tumors. Analysis of Eμ-HDAC9 tumors suggested that HDAC9 might contribute to lymphomagenesis by altering pathways involved in growth and survival, as well as modulating BCL6 activity and p53 tumor suppressor function. Epigenetic modifications play an important role in the germinal center response, and deregulation of the B-cell epigenome as a consequence of mutations and other genomic aberrations are being increasingly recognized as important steps in the pathogenesis of a variety of B-cell lymphomas. A thorough mechanistic understanding of these alterations will inform the use of targeted therapies for these malignancies. These findings strongly suggest a role for HDAC9 in B-NHL and establish a novel GEM model for the study of lymphomagenesis and, potentially, preclinical testing of therapeutic approaches based on histone deacetylase inhibitors.

How I treat double-hit lymphoma.

Science.gov (United States)

Friedberg, Jonathan W

2017-08-03

The 2016 revision of the World Health Organization (WHO) classification for lymphoma has included a new category of lymphoma, separate from diffuse large B-cell lymphoma, termed high-grade B-cell lymphoma with translocations involving myc and bcl-2 or bcl-6 . These lymphomas, which occur in hit lymphomas (or triple-hit lymphomas if all 3 rearrangements are present). It is important to differentiate these lymphomas from the larger group of double-expressor lymphomas, which have increased expression of MYC and BCL-2 and/or BCL-6 by immunohistochemistry, by using variable cutoff percentages to define positivity. Patients with double-hit lymphomas have a poor prognosis when treated with standard chemoimmunotherapy and have increased risk of central nervous system involvement and progression. Double-hit lymphomas may arise as a consequence of the transformation of the underlying indolent lymphoma. There are no published prospective trials in double-hit lymphoma, however retrospective studies strongly suggest that aggressive induction regimens may confer a superior outcome. In this article, I review my approach to the evaluation and treatment of double-hit lymphoma, with an eye toward future clinical trials incorporating rational targeted agents into the therapeutic armamentarium. © 2017 by The American Society of Hematology.

Induction of B-cell lymphoma by UVB Radiation in p53 Haploinsufficient Mice

International Nuclear Information System (INIS)

Puebla-Osorio, Nahum; Miyahara, Yasuko; Coimbatore, Sreevidya; Limón-Flores, Alberto Y; Kazimi, Nasser; Ullrich, Stephen E; Zhu, Chengming

2011-01-01

The incidence of non-Hodgkin's lymphoma has increased over recent years. The exact etiology of lymphoma remains unknown. Ultraviolet light exposure has been associated with the development of internal lymphoid malignancies and some reports suggest that it may play a role in the development of lymphoma in humans. Here we describe the characterization and progression of lymphoma in p53 heterozygous mice exposed to UVB irradiation. UVB-irradiated p53 +/- mice developed enlargement of the spleen. Isolated spleen cells were transplanted into Rag deficient hosts. The UV-induced tumor cells were analyzed by flow cytometry. The tumor cells were tagged with GFP to study their metastatic potential. SKY and karyotypic analysis were carried out for the detection of chromosomal abnormalities. Functional assays included in vitro class switch recombination assay, immunoglobulin rearrangement assay, as well as cytokine profiling. UVB-exposed mice showed enlargement of the spleen and lymph nodes. Cells transplanted into Rag deficient mice developed aggressive tumors that infiltrated the lymph nodes, the spleen and the bone marrow. The tumor cells did not grow in immune competent syngeneic C57Bl/6 mice yet showed a modest growth in UV-irradiated B6 mice. Phenotypic analysis of these tumor cells revealed these cells are positive for B cell markers CD19 + , CD5 + , B220 + , IgM + and negative for T cell, NK or dendritic cell markers. The UV-induced tumor cells underwent robust in vitro immunoglobulin class switch recombination in response to lipopolysaccharide. Cytogenetic analysis revealed a t(14;19) translocation and trisomy of chromosome 6. These tumor cells secret IL-10, which can promote tumor growth and cause systemic immunosuppression. UV-irradiated p53 +/- mice developed lymphoid tumors that corresponded to a mature B cell lymphoma. Our results suggest that an indirect mechanism is involved in the development of internal tumors after chronic exposure to UV light. The

Induction of B-cell lymphoma by UVB Radiation in p53 Haploinsufficient Mice

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Ullrich Stephen E

2011-01-01

Full Text Available Abstract Background The incidence of non-Hodgkin's lymphoma has increased over recent years. The exact etiology of lymphoma remains unknown. Ultraviolet light exposure has been associated with the development of internal lymphoid malignancies and some reports suggest that it may play a role in the development of lymphoma in humans. Here we describe the characterization and progression of lymphoma in p53 heterozygous mice exposed to UVB irradiation. Methods UVB-irradiated p53+/- mice developed enlargement of the spleen. Isolated spleen cells were transplanted into Rag deficient hosts. The UV-induced tumor cells were analyzed by flow cytometry. The tumor cells were tagged with GFP to study their metastatic potential. SKY and karyotypic analysis were carried out for the detection of chromosomal abnormalities. Functional assays included in vitro class switch recombination assay, immunoglobulin rearrangement assay, as well as cytokine profiling. Results UVB-exposed mice showed enlargement of the spleen and lymph nodes. Cells transplanted into Rag deficient mice developed aggressive tumors that infiltrated the lymph nodes, the spleen and the bone marrow. The tumor cells did not grow in immune competent syngeneic C57Bl/6 mice yet showed a modest growth in UV-irradiated B6 mice. Phenotypic analysis of these tumor cells revealed these cells are positive for B cell markers CD19+, CD5+, B220+, IgM+ and negative for T cell, NK or dendritic cell markers. The UV-induced tumor cells underwent robust in vitro immunoglobulin class switch recombination in response to lipopolysaccharide. Cytogenetic analysis revealed a t(14;19 translocation and trisomy of chromosome 6. These tumor cells secret IL-10, which can promote tumor growth and cause systemic immunosuppression. Conclusion UV-irradiated p53+/- mice developed lymphoid tumors that corresponded to a mature B cell lymphoma. Our results suggest that an indirect mechanism is involved in the development of internal

A Circulating microRNA Signature Predicts Age-Based Development of Lymphoma.

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Afshin Beheshti

Full Text Available Extensive epidemiological data have demonstrated an exponential rise in the incidence of non-Hodgkin lymphoma (NHL that is associated with increasing age. The molecular etiology of this remains largely unknown, which impacts the effectiveness of treatment for patients. We proposed that age-dependent circulating microRNA (miRNA signatures in the host influence diffuse large B cell lymphoma (DLBCL development. Our objective was to examine tumor development in an age-based DLBCL system using an inventive systems biology approach. We harnessed a novel murine model of spontaneous DLBCL initiation (Smurf2-deficient at two age groups: 3 and 15 months old. All Smurf2-deficient mice develop visible DLBCL tumor starting at 15 months of age. Total miRNA was isolated from serum, bone marrow and spleen and were collected for all age groups for Smurf2-deficient mice and age-matched wild-type C57BL/6 mice. Using systems biology techniques, we identified a list of 10 circulating miRNAs being regulated in both the spleen and bone marrow that were present in DLBCL forming mice starting at 3 months of age that were not present in the control mice. Furthermore, this miRNA signature was found to occur circulating in the blood and it strongly impacted JUN and MYC oncogenic signaling. In addition, quantification of the miRNA signature was performed via Droplet Digital PCR technology. It was discovered that a key miRNA signature circulates throughout a host prior to the formation of a tumor starting at 3 months old, which becomes further modulated by age and yielded calculation of a 'carcinogenic risk score'. This novel age-based circulating miRNA signature may potentially be leveraged as a DLBCL risk profile at a young age to predict future lymphoma development or disease progression as well as for potential innovative miRNA-based targeted therapeutic strategies in lymphoma.

Immunohistochemical Characterization of Canine Lymphomas

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Roxana CORA

2017-11-01

Full Text Available Lymphomas occur by clonal expansion of lymphoid cells and have distinctive morphological and immunophenotypic features. Determination of canine lymphoma immunophenotype is useful for accurate prognosis and further therapy. In the suggested study, we performed an immunohistochemical evaluation of some cases with canine lymphoma diagnosed in the Department of Pathology (Faculty of Veterinary Medicine, Cluj-Napoca, Romania, in order to characterize them. The investigation included 39 dogs diagnosed with different anatomical forms of lymphoma, following necropsy analysis or assessment of biopsies. The diagnosis of lymphoma was confirmed by necropsy and histopathology (Hematoxylin-eosin stain examinations. The collected specimens were analyzed by immunohistochemistry technique (automatic method using the following antibodies: CD3, CD20, CD21 and CD79a. The analyzed neoplasms were characterized as follows: about 64.10% of cases were diagnosed as B-cell lymphomas, 33.34% of cases as T-cell lymphomas, whereas 2.56% of cases were null cell type lymphomas (neither B nor T. Most of multicentric (80%, mediastinal (60% and primary central nervous system lymphomas (100% had B immunophenotype, while the majority of cutaneous (80% and digestive (100% lymphomas had T immunophenotype. Immunohistochemical description of canine lymphomas can deliver some major details concerning their behavior and malignancy. Additionally, vital prognosis and efficacy of some therapeutic protocols are relying on the immunohistochemical features of canine lymphoma.

Naturally occurring, tumor-specific, therapeutic proteins.

Science.gov (United States)

Argiris, Konstantinos; Panethymitaki, Chrysoula; Tavassoli, Mahvash

2011-05-01

The emerging approach to cancer treatment known as targeted therapies offers hope in improving the treatment of therapy-resistant cancers. Recent understanding of the molecular pathogenesis of cancer has led to the development of targeted novel drugs such as monoclonal antibodies, small molecule inhibitors, mimetics, antisense and small interference RNA-based strategies, among others. These compounds act on specific targets that are believed to contribute to the development and progression of cancers and resistance of tumors to conventional therapies. Delivered individually or combined with chemo- and/or radiotherapy, such novel drugs have produced significant responses in certain types of cancer. Among the most successful novel compounds are those which target tyrosine kinases (imatinib, trastuzumab, sinutinib, cetuximab). However, these compounds can cause severe side-effects as they inhibit pathways such as epidermal growth factor receptor (EGFR) or platelet-derived growth factor receptor, which are also important for normal functions in non-transformed cells. Recently, a number of proteins have been identified which show a remarkable tumor-specific cytotoxic activity. This toxicity is independent of tumor type or specific genetic changes such as p53, pRB or EGFR aberrations. These tumor-specific killer proteins are either derived from common human and animal viruses such as E1A, E4ORF4 and VP3 (apoptin) or of cellular origin, such as TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) and MDA-7 (melanoma differentiation associated-7). This review aims to present a current overview of a selection of these proteins with preferential toxicity among cancer cells and will provide an insight into the possible mechanism of action, tumor specificity and their potential as novel tumor-specific cancer therapeutics.

Burkitts’s lymphoma – an atypical presentation

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Ziade Farah

2012-08-01

Full Text Available Abstract Background In female adolescents and young adults, malignancies of the genital tract are the most frequent type of cancer, closely followed by Hodgkin’s and non-Hodgkin’s lymphomas. Case Presentation We report an unusual case of sporadic Burkitt’s lymphoma (BL presenting with massive bilateral ovarian infiltration, peritoneal carcinomatosis and diffuse nodular lesions of the stomach and the intestine mimicking Krukenberg tumor. Diagnostic biopsies were obtained by endoscopy of the upper gastrointestinal tract. With intensive chemotherapy, complete remission was rapidly achieved, without life-threatening tumor lysis syndrome. Conclusion Besides metastatic gastric adenocarcinoma, BL is an important differential diagnosis in adolescents presenting with Krukenberg tumor.

Primary periosteal lymphoma - rare and unusual

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Abdelwahab, Ibrahim F. [Coney Island Hospital, Department of Radiology, New York, NY (United States); Hoch, Benjamin [Mount Sinai School of Medicine, CUNY, Department of Pathology, New York, NY (United States); Hermann, George [Mount Sinai School of Medicine, CUNY, Department of Radiology, New York, NY (United States); Bianchi, Stefano [Clinique et Fondation des Grangettes, Geneva (Switzerland); Klein, Michael J. [UAB School of Medicine, Department of Pathology, Birmingham, AL (United States); Springfield, Dempsey S. [Mount Sinai School of Medicine, CUNY, Department of Orthopedics, New York, NY (United States)

2007-04-15

We describe a primary periosteal lymphoma that involved only the periosteum without affecting the adjacent medulla or the regional lymph nodes. No other lymphomatous foci were found in either the distant lymph nodes or viscera. This unusual presentation simulates the imaging appearance of surface lesions of bone, namely benign and malignant tumors, and departs from the typical appearance of primary lymphoma of bone. Therefore, this rare type of lymphoma should be considered in the differential diagnosis of surface bone lesions. (orig.)

Clinicopathological study of primary gastric lymphoma

International Nuclear Information System (INIS)

Al-Shehabi, Zubeir A.; Saleh, Rana S.; Zezafon, Hassan B.

2007-01-01

Objective was to present a histopathologic and immunohistochemical analysis of primary gastric lymphomas that was reclassified according to the new World Health Organization classification of lymphoid neoplasms. We reviewed the morphological and immunohistochemical features of 28 patients with gastric lymphomas, diagnosed in the Department of pathology at the University Hospital of Tishreen University, Lattakia, Syria, during the period 1994-2003. Specimens were obtained from endoscopic and surgical biopsies. The immunohistochemical study was performed to analyze the immunophenotype of these lymphomas. Patients were aged 17-71 years. There was a slight predominance of females (male to female ratio, 13:15). Seventeen of the patients had tumors mainly located in the gastric antrum. Histologically, the most common lymphoma was of mucosa-associated lymphoid tissue (MALT) type (20 patients), also with diffuse large B-cell lymphoma (7 patients) and anaplastic large cell lymphoma (one patient). Our study demonstrates the different patterns of gastric lymphomas in Lattakia, Syria during a 10-year period in 28 Syrian patients, and reveals that the most primary gastric lymphomas are B-cell MALT lymphomas. (author)

Epigenetic regulation of CD44 in Hodgkin and non-Hodgkin lymphoma

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Eberth, Sonja; Schneider, Björn; Rosenwald, Andreas; Hartmann, Elena M; Romani, Julia; Zaborski, Margarete; Siebert, Reiner; Drexler, Hans G; Quentmeier, Hilmar

2010-01-01

Epigenetic inactivation of tumor suppressor genes (TSG) by promoter CpG island hypermethylation is a hallmark of cancer. To assay its extent in human lymphoma, methylation of 24 TSG was analyzed in lymphoma-derived cell lines as well as in patient samples. We screened for TSG methylation using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) in 40 lymphoma-derived cell lines representing anaplastic large cell lymphoma, Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), Hodgkin lymphoma and mantle cell lymphoma (MCL) as well as in 50 primary lymphoma samples. The methylation status of differentially methylated CD44 was verified by methylation-specific PCR and bisulfite sequencing. Gene expression of CD44 and its reactivation by DNA demethylation was determined by quantitative real-time PCR and on the protein level by flow cytometry. Induction of apoptosis by anti-CD44 antibody was analyzed by annexin-V/PI staining and flow cytometry. On average 8 ± 2.8 of 24 TSG were methylated per lymphoma cell line and 2.4 ± 2 of 24 TSG in primary lymphomas, whereas 0/24 TSG were methylated in tonsils and blood mononuclear cells from healthy donors. Notably, we identified that CD44 was hypermethylated and transcriptionally silenced in all BL and most FL and DLBCL cell lines, but was usually unmethylated and expressed in MCL cell lines. Concordant results were obtained from primary lymphoma material: CD44 was not methylated in MCL patients (0/11) whereas CD44 was frequently hypermethylated in BL patients (18/29). In cell lines with CD44 hypermethylation, expression was re-inducible at mRNA and protein levels by treatment with the DNA demethylating agent 5-Aza-2'-deoxycytidine, confirming epigenetic regulation of CD44. CD44 ligation assays with a monoclonal anti-CD44 antibody showed that CD44 can mediate apoptosis in CD44 + lymphoma cells. CD44 hypermethylated, CD44 - lymphoma cell lines were consistently

Primary thyroid lymphoma: CT findings

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Kim, Hyo-Cheol; Han, Moon Hee E-mail: hanmh@radcom.snu.ac.kr; Kim, Keon Ha; Jae, Hwan Jun; Lee, Sang Hyun; Kim, Sam Soo; Kim, Kwang Hyun; Chang, Kee-Hyun

2003-06-01

Introduction: To evaluate the computed tomographic (CT) findings of primary thyroid lymphoma. Methods and material: The clinicopathological data and CT images of nine patients with primary thyroid lymphoma were retrospectively reviewed. The CT appearances were classified into three types: type 1, a solitary nodule surrounded by normal thyroid tissue; type 2, multiple nodules in the thyroid, and type 3, a homogeneously enlarged both thyroid glands with a reduced attenuation with or without peripheral thin hyperattenuating thyroid tissue. Results: All patients had a rapidly enlarging thyroid mass and coexistent Hashimoto's thyroiditis. One patient showed type 1 pattern, three type 2, and five type 3. Six patients had homogeneous tumor isoattenuating to surrounding muscles. The tumors had a strong tendency to compress normal remnant thyroid and the surrounding structure without invasion. Conclusion: Primary thyroid lymphoma should be included in the differential diagnosis when old female had a homogeneous thyroidal mass isoattenuating to muscles, which does not invade surrounding structures.

Novel Therapeutic Targets to Inhibit Tumor Microenvironment Induced Castration-Resistant Prostate Cancer

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2017-12-01

AWARD NUMBER: W81XWH-13-1-0163 TITLE: Novel Therapeutic Targets to Inhibit Tumor Microenvironment Induced Castration-resistant Prostate Cancer ...Prostate Cancer 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Feng Yang, Ph.D. 5d. PROJECT NUMBER 5e. TASK NUMBER E-Mail: fyang@bcm.edu...W81XWH-13-1-0163 " Novel Therapeutic Targets to Inhibit Tumor Microenvironment Induced Castration-resistant Prostate Cancer " Introduction AR signaling

The Prognostic, Diagnostic, and Therapeutic Potential of Tumor Antigens

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Olsen, Lars Rønn

or abundance in cancer cells is often unique and their roles and functions in tumorigenesis are, in many cases, studied extensively. They, therefore, have the potential to be highly specific biomarkers as well as therapeutic targets, but complex analysis combining basic science, high-throughput methods...... of genomics and proteomics, and clinical studies need to be combined. These analyses produce large amounts of data that require advanced bioinformatics methods for collection, management, integration and interpretation. In this thesis, I have explored the potential of tumor antigens as biomarkers...... and therapeutic agents, by developing and implementing several computational tools and databases for immunotherapy target discovery, and have analyzed the potential of tumor antigens as proteogenomic biomarkers in invasive ductal carcinomas. In this analysis I have shown that the combination of proteomics...

Primary brain lymphoma in a patient after renal transplantation

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Arteaga, Carlos; Duarte, Monica; Bayona, Hernan

2009-01-01

The incidence of primary central nervous system lymphoma (PCNSL) has increased during the past 40 years. This has been associated with immunodeficiency, mainly in patients infected with the human immunodeficiency virus (HIV) and in transplant patients. Tumor genesis is related with the Epstein-Barr virus (EBV). The most frequent PCNSL immuno phenotype is B-cell lymphoma. Clinical manifestations depend on tumor localization, and are usually behavior dysfunctions and intracranial hypertension syndrome. Differential diagnosis must take into consideration infectious processes, stroke, primary brain tumors, and metastases. The diagnosis of PCNSL requires brain MRI and brain biopsy. It is important to assess HIV infection when diagnosing PCNSL. This review reports a case of primary brain lymphoma in a patient who underwent renal transplantation due to polycystic kidney disease 8 years before.

Appendiceal and ovarian Burkitt's lymphoma presenting as acute appendicitis

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Donovan Hui

2018-05-01

Full Text Available Burkitt's lymphoma is an extremely aggressive B-cell non-Hodgkin lymphoma. Patients with the sporadic form of Burkitt's lymphoma typically present with a rapidly growing abdominal mass, pain and distension. Involvement of either the appendix and/or ovaries in females is a rare manifestation of the disease. We present an unusual case of a 13 year old girl with appendiceal and ovarian Burkitt's lymphoma presenting with signs of acute appendicitis. This case demonstrates the potential for secondary involvement of the appendix and/or ovaries from Burkitt's lymphoma as well as the importance of the histopathology. Keywords: Appendicitis, Appendix, Burkitt's lymphoma, Lymphoma, Ovarian tumor

Epigenetic profiling of cutaneous T-cell lymphoma: promoter hypermethylation of multiple tumor suppressor genes including BCL7a, PTPRG, and p73.

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van Doorn, Remco; Zoutman, Willem H; Dijkman, Remco; de Menezes, Renee X; Commandeur, Suzan; Mulder, Aat A; van der Velden, Pieter A; Vermeer, Maarten H; Willemze, Rein; Yan, Pearlly S; Huang, Tim H; Tensen, Cornelis P

2005-06-10

To analyze the occurrence of promoter hypermethylation in primary cutaneous T-cell lymphoma (CTCL) on a genome-wide scale, focusing on epigenetic alterations with pathogenetic significance. DNA isolated from biopsy specimens of 28 patients with CTCL, including aggressive CTCL entities (transformed mycosis fungoides and CD30-negative large T-cell lymphoma) and an indolent entity (CD30-positive large T-cell lymphoma), were investigated. For genome-wide DNA methylation screening, differential methylation hybridization using CpG island microarrays was applied, which allows simultaneous detection of the methylation status of 8640 CpG islands. Bisulfite sequence analysis was applied for confirmation and detection of hypermethylation of eight selected tumor suppressor genes. The DNA methylation patterns of CTCLs emerging from differential methylation hybridization analysis included 35 CpG islands hypermethylated in at least four of the 28 studied CTCL samples when compared with benign T-cell samples. Hypermethylation of the putative tumor suppressor genes BCL7a (in 48% of CTCL samples), PTPRG (27%), and thrombospondin 4 (52%) was confirmed and demonstrated to be associated with transcriptional downregulation. BCL7a was hypermethylated at a higher frequency in aggressive (64%) than in indolent (14%) CTCL entities. In addition, the promoters of the selected tumor suppressor genes p73 (48%), p16 (33%), CHFR (19%), p15 (10%), and TMS1 (10%) were hypermethylated in CTCL. Malignant T cells of patients with CTCL display widespread promoter hypermethylation associated with inactivation of several tumor suppressor genes involved in DNA repair, cell cycle, and apoptosis signaling pathways. In view of this, CTCL may be amenable to treatment with demethylating agents.

Nanoparticles—Emerging Potential for Managing Leukemia and Lymphoma

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Raquel Vinhas

2017-12-01

Full Text Available Nanotechnology has become a powerful approach to improve the way we diagnose and treat cancer. In particular, nanoparticles (NPs possess unique features for enhanced sensitivity and selectivity for earlier detection of circulating cancer biomarkers. In vivo, NPs enhance the therapeutic efficacy of anticancer agents when compared with conventional chemotherapy, improving vectorization and delivery, and helping to overcome drug resistance. Nanomedicine has been mostly focused on solid cancers due to take advantage from the enhanced permeability and retention (EPR effect experienced by tissues in the close vicinity of tumors, which enhance nanomedicine’s accumulation and, consequently, improve efficacy. Nanomedicines for leukemia and lymphoma, where EPR effect is not a factor, are addressed differently from solid tumors. Nevertheless, NPs have provided innovative approaches to simple and non-invasive methodologies for diagnosis and treatment in liquid tumors. In this review, we consider the state of the art on different types of nanoconstructs for the management of liquid tumors, from preclinical studies to clinical trials. We also discuss the advantages of nanoplatforms for theranostics and the central role played by NPs in this combined strategy.

Application of Mesenchymal Stem Cells for Therapeutic Agent Delivery in Anti-tumor Treatment

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Daria S. Chulpanova

2018-03-01

Full Text Available Mesenchymal stem cells (MSCs are non-hematopoietic progenitor cells, which can be isolated from different types of tissues including bone marrow, adipose tissue, tooth pulp, and placenta/umbilical cord blood. There isolation from adult tissues circumvents the ethical concerns of working with embryonic or fetal stem cells, whilst still providing cells capable of differentiating into various cell lineages, such as adipocytes, osteocytes and chondrocytes. An important feature of MSCs is the low immunogenicity due to the lack of co-stimulatory molecules expression, meaning there is no need for immunosuppression during allogenic transplantation. The tropism of MSCs to damaged tissues and tumor sites makes them a promising vector for therapeutic agent delivery to tumors and metastatic niches. MSCs can be genetically modified by virus vectors to encode tumor suppressor genes, immunomodulating cytokines and their combinations, other therapeutic approaches include MSCs priming/loading with chemotherapeutic drugs or nanoparticles. MSCs derived membrane microvesicles (MVs, which play an important role in intercellular communication, are also considered as a new therapeutic agent and drug delivery vector. Recruited by the tumor, MSCs can exhibit both pro- and anti-oncogenic properties. In this regard, for the development of new methods for cancer therapy using MSCs, a deeper understanding of the molecular and cellular interactions between MSCs and the tumor microenvironment is necessary. In this review, we discuss MSC and tumor interaction mechanisms and review the new therapeutic strategies using MSCs and MSCs derived MVs for cancer treatment.

Lymphoma and metastases in the urinary tract

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Bruneton, J.N.; Drouillard, J.

1989-01-01

Kidneys lymphomas are mainly secondary and represent the most frequent localizations in the urinary tract (68%). The appearance most frequently observed with computed tomography (CT) as well as ultrasound is that of multinodular involvement or, less frequently, of contiguous involvement from retroperitoneal adenopathy in an isolate nodular or tumoral form or in an infiltrating form. The lesions are most often bilateral and involve the lymph nodes, the liver and/or the spleen, especially when the tumor is a metastasis. Lymphoma in the excreting cavities of the bladder is much less frequent. The frequent stasis does no allow obtaining satisfactory urograms for the exploration of the ureters, so that antegrade or retrograde pyelography is often necessary. The lesions of the bladder are well demonstrated by ultrasound and CT exploration. The metastases of lymphoma in the urinary tract are most frequently located in the kidneys, and represent the most frequent malignant kidney tumors. They are often non recognized clinically since they occur at late stages in cancer evolution. Their usual appearance with ultrasound and CT is that of multiple solid-type tumors. Metastases in the excreting cavities of the bladder are very rare [fr

Distinct patterns of HIV-1 evolution within metastatic tissues in patients with non-Hodgkins lymphoma.

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Marco Salemi

2009-12-01

Full Text Available Despite highly active antiretroviral therapy (HAART, AIDS related lymphoma (ARL occurs at a significantly higher rate in patients infected with the Human Immunodeficiency Virus (HIV than in the general population. HIV-infected macrophages are a known viral reservoir and have been shown to have lymphomagenic potential in SCID mice; therefore, there is an interest in determining if a viral component to lymphomagenesis also exists. We sequenced HIV-1 envelope gp120 clones obtained post mortem from several tumor and non-tumor tissues of two patients who died with AIDS-related Non-Hodgkin's lymphoma (ARL-NH. Similar results were found in both patients: 1 high-resolution phylogenetic analysis showed a significant degree of compartmentalization between lymphoma and non-lymphoma viral sub-populations while viral sub-populations from lymph nodes appeared to be intermixed within sequences from tumor and non-tumor tissues, 2 a 100-fold increase in the effective HIV population size in tumor versus non-tumor tissues was associated with the emergence of lymphadenopathy and aggressive metastatic ARL, and 3 HIV gene flow among lymph nodes, normal and metastatic tissues was non-random. The different population dynamics between the viruses found in tumors versus the non-tumor associated viruses suggest that there is a significant relationship between HIV evolution and lymphoma pathogenesis. Moreover, the study indicates that HIV could be used as an effective marker to study the origin and dissemination of lymphomas in vivo.

[Antitumor effects of matrix protein of vesicular stomatic virus on EL4 lymphoma mice].

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Lin, Shi-jia; Yu, Qin-mei; Meng, Wen-tong; Wen, Yan-jun; Chen, Li-juan; Niu, Ting

2011-03-01

To explore antitumor effects of plasmid pcDNA3. 1-MP encoding matrix protein of vesicular stomatitis virus (VSV) complexed with cationic liposome (DOTAP:CHOL) in mice with EL4 lymphoma. C57BL/6 mouse model with EL4 lymphoma was established. Sixty mice bearing EL4 lymphoma were divided randomly into five groups including Lip-MP, Lip-pVAX, Lip, ADM and NS groups, which were intravenously injected with liposome-pcDNA 3. 1-MP complex, liposome-pVAX complex, empty liposome, Adriamycin and normal saline respectively every three days. Tumor volumes and survival time were monitored. Microvessel density and tumor proliferative index in tumor tissues were determined by CD31, Ki-67 immunohistochemistry staining, meanwhile the tumor apoptosis index was measured by TUNEL method. From 6 days after treatments on, the tumor volume in Lip-MP group was much smaller than that in Lip-pVAX, Lip and NS group (P EL4 tumor cells in vivo (P EL4 lymphoma, which may be related to the induction of tumor cell apoptosis, inhibition of tumor angiogenesis, and suppression of tumor cell proliferation.

Therapeutics targeting tumor immune escape: towards the development of new generation anticancer vaccines.

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Mocellin, Simone; Nitti, Donato

2008-05-01

Despite the evidence that immune effectors can play a significant role in controlling tumor growth under natural conditions or in response to therapeutic manipulation, it is clear that malignant cells evade immune surveillance in most cases. Considering that anticancer vaccination has reached a plateau of results and currently no vaccination regimen is indicated as a standard anticancer therapy, the dissection of the molecular events underlying tumor immune escape is the necessary condition to make anticancer vaccines a therapeutic weapon effective enough to be implemented in the routine clinical setting. Recent years have witnessed significant advances in our understanding of the molecular mechanisms underlying tumor immune escape. These mechanistic insights are fostering the development of rationally designed therapeutics aimed at reverting the immunosuppressive circuits that undermine an effective antitumor immune response. In this review, the best characterized mechanisms that allow cancer cells to evade immune surveillance are overviewed and the most debated controversies constellating this complex field are highlighted. In addition, the latest therapeutic strategies devised to overcome tumor immune escape are described, with special regard to those entering clinical phase investigation. Copyright (c) 2007 Wiley-Periodicals, Inc.

Systemic non-Hodgkin's lymphoma initially presenting as a bladder mass

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Naveen Kumar Gupta

2017-01-01

Full Text Available Urinary bladder lymphomas are rare lesions which may be primary bladder lymphomas or part of systemic lymphoma with bladder involvement. We report a case of non-Hodgkin's lymphoma (NHL in a 73-year-old female who presented with bladder tumor which on evaluation revealed NHL with extensive systemic involvement. The management of such an advanced case is discussed here with literature review.

Vorinostat and Decitabine in Treating Patients With Advanced Solid Tumors or Relapsed or Refractory Non-Hodgkin's Lymphoma, Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, or Chronic Myelogenous Leukemia

Science.gov (United States)

2014-08-26

; Stage IV Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

MicroRNA181a Is Overexpressed in T-Cell Leukemia/Lymphoma and Related to Chemoresistance

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Zi-Xun Yan

2015-01-01

Full Text Available MicroRNAs (miRs play an important role in tumorogenesis and chemoresistance in lymphoid malignancies. Comparing with reactive hyperplasia, miR181a was overexpressed in 130 patients with T-cell leukemia/lymphoma, including acute T-cell lymphoblastic leukemia (n=32, T-cell lymphoblastic lymphoma (n=16, peripheral T-cell lymphoma, not otherwise specified (n=45, anaplastic large cell lymphoma (n=15, and angioimmunoblastic T-cell lymphoma (n=22. Irrespective to histological subtypes, miR181a overexpression was associated with increased AKT phosphorylation. In vitro, ectopic expression of miR181a in HEK-293T cells significantly enhanced cell proliferation, activated AKT, and conferred cell resistance to doxorubicin. Meanwhile, miR181a expression was upregulated in Jurkat cells, along with AKT activation, during exposure to chemotherapeutic agents regularly applied to T-cell leukemia/lymphoma treatment, such as doxorubicin, cyclophosphamide, cytarabine, and cisplatin. Isogenic doxorubicin-resistant Jurkat and H9 cells were subsequently developed, which also presented with miR181a overexpression and cross-resistance to cyclophosphamide and cisplatin. Meanwhile, specific inhibition of miR181a enhanced Jurkat and H9 cell sensitivity to chemotherapeutic agents, further indicating that miR181a was involved in acquired chemoresistance. Collectively, miR181a functioned as a biomarker of T-cell leukemia/lymphoma through modulation of AKT pathway. Related to tumor cell chemoresistance, miR181a could be a potential therapeutic target in treating T-cell malignancies.

Intraocular lymphoma

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Li-Juan Tang

2017-08-01

Full Text Available Intraocular lymphoma (IOL is a rare lymphocytic malignancy which contains two main distinct forms. Primary intraocular lymphoma (PIOL is mainly a sub-type of primary central nervous system lymphoma (PCNSL. Alternatively, IOL can originate from outside the central nervous system (CNS by metastasizing to the eye. These tumors are known as secondary intraocular lymphoma (SIOL. The IOL can arise in the retina, uvea, vitreous, Bruch’s membrane and optic nerve. There are predominantly of B-cell origin; however there are also rare T-cell variants. Diagnosis remains challenging for ophthalmologists and pathologists, due to its ability to masquerade as noninfectious or infectious uveitis, white dot syndromes, or occasionally as other metastatic cancers. Laboratory tests include flow cytometry, immunocytochemistry, interleukin detection (IL-10: IL-6, ratio >1, and polymerase chain reaction (PCR amplification. Methotrexate-based systemic chemotherapy with external beam radiotherapy and intravitreal chemotherapy with methotrexate are useful for controlling the disease, but the prognosis remains poor. Therefore, it is important to make an early diagnose and treatment. This review is focused on the clinical manifestations, diagnosis, treatment and prognosis of the IOL.

A mechanistic compartmental model for total antibody uptake in tumors.

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Thurber, Greg M; Dane Wittrup, K

2012-12-07

Antibodies are under development to treat a variety of cancers, such as lymphomas, colon, and breast cancer. A major limitation to greater efficacy for this class of drugs is poor distribution in vivo. Localization of antibodies occurs slowly, often in insufficient therapeutic amounts, and distributes heterogeneously throughout the tumor. While the microdistribution around individual vessels is important for many therapies, the total amount of antibody localized in the tumor is paramount for many applications such as imaging, determining the therapeutic index with antibody drug conjugates, and dosing in radioimmunotherapy. With imaging and pretargeted therapeutic strategies, the time course of uptake is critical in determining when to take an image or deliver a secondary reagent. We present here a simple mechanistic model of antibody uptake and retention that captures the major rates that determine the time course of antibody concentration within a tumor including dose, affinity, plasma clearance, target expression, internalization, permeability, and vascularization. Since many of the parameters are known or can be estimated in vitro, this model can approximate the time course of antibody concentration in tumors to aid in experimental design, data interpretation, and strategies to improve localization. Copyright © 2012 Elsevier Ltd. All rights reserved.

CD5-Positive Primary Intraocular B-Cell Lymphoma Arising during Methotrexate and Tumor Necrosis Factor Inhibitor Treatment

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Kenji Nagata

2015-09-01

Full Text Available Purpose: To report a case of CD5+ primary intraocular B-cell lymphoma arising during methotrexate (MTX and tumor necrosis factor (TNF inhibitor treatment in a young patient with rheumatoid arthritis and uveitis. Case Presentation: A 39-year-old woman treated with MTX and a TNF inhibitor for rheumatoid arthritis and uveitis had steroid-resistant vitreous opacity. A vitreous sample was obtained by using diagnostic vitrectomy and was categorized as class V based on cytologic examination. Flow cytometric analysis of the vitreous sample revealed that abnormal cells were CD5+, CD10-, CD19+, CD20+ and immunoglobulin light-chain kappa+, suggesting the diagnosis of CD5+ primary intraocular B-cell lymphoma. Polymerase chain reaction (PCR detected immunoglobulin heavy-chain gene rearrangement. Epstein-Barr virus (EBV DNA was detected in the vitreous sample by using PCR, and immunohistochemistry revealed EBV latent membrane protein-1 expression in the abnormal cells infiltrating the vitreous. Optic nerve invasion was observed on magnetic resonance imaging. Conclusion: Primary intraocular lymphoma (PIOL may develop in patients receiving MTX and TNF inhibitor treatment. EBV infection may play an important role in the pathogenesis of PIOL arising during immunosuppressive therapy.

Lym-1 Chimeric Antigen Receptor T Cells Exhibit Potent Anti-Tumor Effects against B-Cell Lymphoma

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Long Zheng

2017-12-01

Full Text Available T cells expressing chimeric antigen receptors (CARs recognizing CD19 epitopes have produced remarkable anti-tumor effects in patients with B-cell malignancies. However, cancer cells lacking recognized epitopes can emerge, leading to relapse and death. Thus, CAR T cells targeting different epitopes on different antigens could improve immunotherapy. The Lym-1 antibody targets a conformational epitope of Human Leukocyte Antigen-antigen D Related (HLA-DR on the surface of human B-cell lymphomas. Lym-1 CAR T cells were thus generated for evaluation of cytotoxic activity towards lymphoma cells in vitro and in vivo. Human T cells from healthy donors were transduced to express a Lym-1 CAR, and assessed for epitope-driven function in culture and towards Raji xenografts in NOD-scidIL2Rgammanull (NSG mice. Lym-1 CAR T cells exhibited epitope-driven activation and lytic function against human B-cell lymphoma cell lines in culture and mediated complete regression of Raji/Luciferase-Green fluorescent protein (Raji/Luc-GFP in NSG mice with similar or better reactivity than CD19 CAR T cells. Lym-1 CAR transduction of T cells is a promising immunotherapy for patients with Lym-1 epitope positive B-cell malignancies.

Irradiation promotes Akt-targeting therapeutic gene delivery to the tumor vasculature

International Nuclear Information System (INIS)

Sonveaux, Pierre; Frerart, Francoise; Bouzin, Caroline; Brouet, Agnes; Wever, Julie de; Jordan, Benedicte F.; Gallez, Bernard; Feron, Olivier

2007-01-01

Purpose: To determine whether radiation-induced increases in nitric oxide (NO) production can influence tumor blood flow and improve delivery of Akt-targeting therapeutic DNA lipocomplexes to the tumor. Methods and Materials: The contribution of NO to the endothelial response to radiation was identified using NO synthase (NOS) inhibitors and endothelial NOS (eNOS)-deficient mice. Reporter-encoding plasmids complexed with cationic lipids were used to document the tumor vascular specificity and the efficacy of in vivo lipofection after irradiation. A dominant-negative Akt gene construct was used to evaluate the facilitating effects of radiotherapy on the therapeutic transgene delivery. Results: The abundance of eNOS protein was increased in both irradiated tumor microvessels and endothelial cells, leading to a stimulation of NO release and an associated increase in tumor blood flow. Transgene expression was subsequently improved in the irradiated vs. nonirradiated tumor vasculature. This effect was not apparent in eNOS-deficient mice and could not be reproduced in irradiated cultured endothelial cells. Finally, we combined low-dose radiotherapy with a dominant-negative Akt gene construct and documented synergistic antitumor effects. Conclusions: This study offers a new rationale to combine radiotherapy with gene therapy, by directly exploiting the stimulatory effects of radiation on NO production by tumor endothelial cells. The preferential expression of the transgene in the tumor microvasculature underscores the potential of such an adjuvant strategy to limit the angiogenic response of irradiated tumors

IMMUNOTHERAPY FOR EPSTEIN-BARR VIRUS-RELATED LYMPHOMAS

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Helen Heslop

2009-11-01

Full Text Available

Latent EBV infection is associated with several malignancies, including EBV post-transplant lymphoproliferative disorders (LPD, Hodgkin and non-Hodgkin lymphomas, nasopharyngeal carcinoma and Burkitt lymphoma. The range of expression of latent EBV antigens varies in these tumors, which influences how susceptible the tumors are to immunotherapeutic approaches. Tumors expressing type III latency, such as in LPD, express the widest array of EBV antigens making them the most susceptible to immunotherapy. Treatment strategies for EBV-related tumors include restoring normal cellular immunity by adoptive immunotherapy with EBV-specific T cells and targeting the malignant B cells with monoclonal antibodies. We review the current immunotherapies and future studies aimed at targeting EBV antigen expression in these tumors.

[First-line treatment of lymphomas of "high grade malignancy" or "aggressive lymphomas"].

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Reyes, F

2001-11-01

Main strategies used as first line treatment of aggressive lymphoma are the subject of this review. The evolution of histopathlogical classifications is reviewed and the concept of aggressive lymphoma is given. General principles of chemotherapy treatment and main prognostic factors that direct therapeutic decisions are described. The treatment modalities of localized and advanced disease are detailed, as well as the role of high-dose therapy with hematopoietic support. Finally, the major impact of immunotherapy based on the monoclonal anti-CD20 antibody is envisaged.

Biphasic Rapamycin Effects in Lymphoma and Carcinoma Treatment.

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Liu, Yang; Pandeswara, Srilakshmi; Dao, Vinh; Padrón, Álvaro; Drerup, Justin M; Lao, Shunhua; Liu, Aijie; Hurez, Vincent; Curiel, Tyler J

2017-01-15

mTOR drives tumor growth but also supports T-cell function, rendering the applications of mTOR inhibitors complex especially in T-cell malignancies. Here, we studied the effects of the mTOR inhibitor rapamycin in mouse EL4 T-cell lymphoma. Typical pharmacologic rapamycin (1-8 mg/kg) significantly reduced tumor burden via direct suppression of tumor cell proliferation and improved survival in EL4 challenge independent of antitumor immunity. Denileukin diftitox (DD)-mediated depletion of regulatory T cells significantly slowed EL4 growth in vivo in a T-cell-dependent fashion. However, typical rapamycin inhibited T-cell activation and tumor infiltration in vivo and failed to boost DD treatment effects. Low-dose (LD) rapamycin (75 μg/kg) increased potentially beneficial CD44hiCD62L + CD8 + central memory T cells in EL4 challenge, but without clinical benefit. LD rapamycin significantly enhanced DD treatment efficacy, but DD plus LD rapamycin treatment effects were independent of antitumor immunity. Instead, rapamycin upregulated EL4 IL2 receptor in vitro and in vivo, facilitating direct DD tumor cell killing. LD rapamycin augmented DD efficacy against B16 melanoma and a human B-cell lymphoma, but not against human Jurkat T-cell lymphoma or ID8agg ovarian cancer cells. Treatment effects correlated with IL2R expression, but mechanisms in some tumors were not fully defined. Overall, our data define a distinct, biphasic mechanisms of action of mTOR inhibition at doses that are clinically exploitable, including in T-cell lymphomas. Cancer Res; 77(2); 520-31. ©2016 AACR. ©2016 American Association for Cancer Research.

Chemotherapy synergizes with radioimmunotherapy targeting La autoantigen in tumors.

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Fares Al-Ejeh

Full Text Available To date, inefficient delivery of therapeutic doses of radionuclides to solid tumors limits the clinical utility of radioimmunotherapy. We aim to test the therapeutic utility of Yttrium-90 ((90Y-radio-conjugates of a monoclonal antibody, which we showed previously to bind specifically to the abundant intracellular La ribonucleoprotein revealed in dead tumor cells after DNA-damaging treatment.Immunoconjugates of the DAB4 clone of the La-specific monoclonal antibody, APOMAB, were prepared using the metal chelator, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA, and then radiolabeled with (90Y. Mice bearing established subcutaneous tumors were treated with (90Y-DOTA-DAB4 alone or after chemotherapy. Non-radiosensitizing cyclophosphamide/etoposide chemotherapy was used for the syngeneic EL4 lymphoma model. Radiosensitizing cisplatin/gemcitabine chemotherapy was used for the syngeneic Lewis Lung carcinoma (LL2 model, and for the xenograft models of LNCaP prostatic carcinoma and Panc-1 pancreatic carcinoma. We demonstrate the safety, specificity, and efficacy of (90Y-DOTA-DAB4-radioimmunotherapy alone or combined with chemotherapy. EL4 lymphoma-bearing mice either were cured at higher doses of radioimmunotherapy alone or lower doses of radioimmunotherapy in synergy with chemotherapy. Radioimmunotherapy alone was less effective in chemo- and radio-resistant carcinoma models. However, radioimmunotherapy synergized with radiosensitizing chemotherapy to retard significantly tumor regrowth and so prolong the survival of mice bearing LL2, LNCaP, or Panc-1 subcutaneous tumor implants.We report proof-of-concept data supporting a unique form of radioimmunotherapy, which delivers bystander killing to viable cancer cells after targeting the universal cancer antigen, La, created by DNA-damaging treatment in neighboring dead cancer cells. Subsequently we propose that DAB4-targeted ionizing radiation induces additional cycles of tumor cell death

Unusual Origin and Rare Presentation of Primary Cardiac Lymphoma

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Mohamed, Amir; Cherian, Sanjay; El-Ashmawy, Ahmed; Abdelmoneim, Salah Eldin; Soliman, Maher; Abu-Rayan, Mohamed; Kalangos, Afksendyios

2011-01-01

Non-Hodgkin lymphoblastic lymphomas are very uncommon tumors that rarely involve the heart; however, when they do, they typically cause cardiac symptoms. Herein, we describe the case of a young woman who presented with respiratory symptoms. These were caused by a high-grade lymphoblastic lymphoma, which originated in the left inferior pulmonary vein and extended into the left atrium. The tumor was surgically debulked, but it recurred in 1 month, and the patient underwent chemotherapy. Six months later, she had recurrent respiratory symptoms, and echocardiography revealed a persistent mass in the left lower lobar vein. A modified chemotherapy regimen led to complete resolution of the tumor within 2 months. We are unaware of other reports of a primary cardiac non-Hodgkin lymphoblastic lymphoma with this unusual site of origin and rare manifestation of symptoms. PMID:21841872

Radiation carcinogenesis in mouse thymic lymphomas

International Nuclear Information System (INIS)

Kominami, Ryo; Niwa, Ohtsura

2006-01-01

Ionizing radiation is a well-known carcinogen for various human tissues and a complete carcinogen that is able to initiate and promote neoplastic progression. Studies of radiation-induced mouse thymic lymphomas, one of the classic models in radiation carcinogenesis, demonstrated that even the unirradiated thymus is capable of developing into full malignancy when transplanted into the kidney capsule or subcutaneous tissue of irradiated mice. This suggests that radiation targets tissues other than thymocytes to allow expansion of cells with tumorigenic potential in the thymus. The idea is regarded as the ''indirect mechanism'' for tumor development. This paper reviews the indirect mechanism and genes affecting the development of thymic lymphomas that we have analyzed. One is the Bcl11b/Rit1 tumor suppressor gene and the other is Mtf-1 gene affecting tumor susceptibility. (author)

BONE TUMOR ENVIRONMENT AS POTENTIAL THERAPEUTIC TARGET IN EWING SARCOMA

Directory of Open Access Journals (Sweden)

Françoise eREDINI

2015-12-01

Full Text Available Ewing sarcoma is the second most common pediatric bone tumor, with three cases per million worldwide. In clinical terms, ES is an aggressive, rapidly fatal malignancy that mainly develops in osseous sites (85%, but also in extraskeletal soft tissue. It spreads naturally to the lungs, bones and bone marrow with poor prognosis in the two latter cases. Bone lesions from primary or secondary (metastases tumors are characterized by extensive bone remodeling, more often due to osteolysis. Osteoclast activation and subsequent bone resorption is responsible for the clinical features of bone tumors including pain, vertebral collapse and spinal cord compression. Based on the vicious cycle concept of tumor cells and bone resorbing cells, drugs which target osteoclasts may be promising agents as adjuvant setting for treating bone tumors, including Ewing sarcoma. There is also increasing evidence that cellular and molecular protagonists present in the bone microenvironment play a part in establishing a favorable niche for tumor initiation and progression. The purpose of this review is to discuss the potential therapeutic value of drugs targeting the bone tumor microenvironment in Ewing Sarcoma. The first part of the review will focus on targeting the bone resorbing function of osteoclasts by means of bisphosphonates (BPs or drugs blocking the pro-resorbing cytokine Receptor Activator of NF-kappa B Ligand (RANKL. Second, the role of this peculiar hypoxic microenvironment will be discussed in the context of resistance to chemotherapy, escape from the immune system, or neo-angiogenesis. Therapeutic interventions based on these specificities could be then proposed in the context of Ewing sarcoma.

A Color-coded Imageable Syngeneic Mouse Model of Stromal-cell Recruitment by Metastatic Lymphoma.

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Matsumoto, Takuro; Suetsugu, Atsushi; Shibata, Yuhei; Nakamura, Nobuhiko; Aoki, Hitomi; Kunisada, Takahiro; Tsurumi, Hisashi; Shimizu, Masahito; Hoffman, Robert M

2015-09-01

A syngeneic color-coded imageable lymphoma model has been developed to visualize recruitment of host stromal cells by malignant lymphoma during metastasis. The EL4 cell line was previously derived from a lymphoma induced in a C57/BL6 mouse by 9,10-dimethyl-1,2-benzanthracene. EL4 lymphoma cells expressing red fluorescent protein (EL4-RFP) were initially established. EL4-RFP cells were subsequently injected into the tail vein of C57/BL6-GFP transgenic mice. EL4-RFP metastasis was observed in the lymph nodes of the upper mediastinum and in the liver 28 days after cell injection. Large EL4-RFP liver metastases in C57/BL6-GFP mice contained GFP-expressing stromal cells derived from the host. In addition, EL4-RFP lymphoma metastasis was formed in peri-gastric lymph nodes, which were also enriched in host GFP-expressing cells. Furthermore, EL4-RFP lymphoma cells were also observed in the peripheral blood and bone marrow of C57/BL6-GFP transgenic mice, where they were associated with GFP-expressing host cells. Lymph node, liver and bone marrow metastases were found approximately 4 weeks after transplantation and all RFP-expressing metastases were highly enriched in GFP-expressing host stromal cells. This model of malignant lymphoma can be used to study early tumor development, metastasis, and the role of the stroma, as well as for discovery and evaluation of novel therapeutics for this treatment-resistant disease. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Risk interrelationship among multiple primary tumors

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Safi, Mohammed; Sun, Xiuhua; Wang, Lifen; Zhang, Xinwei; Song, Jicheng; Ameen, Mohammed

2018-01-01

Abstract Rationale: Along with advanced management in oncology, great progress has been recently achieved in the studies of multiple primary tumors. Several reports have studied the coexistence between lymphoma and either renal cell carcinoma (RCC) or Warthin tumor. However, the level of coexistence between these cases remains unclear due to the absence of a distinct link between them. Patient concerns: We present a unique case of multiple primary tumors (lymphoma, RCC, and Warthin tumor) in an 80-year-old man and a review of the literature on the coexistence of RCC with lymphoma and lymphoma with Warthin tumor. Diagnosis: With a history of RCC, the patient had a freely movable lump under his left ear, and the pathological report indicated Hodgkin lymphoma and Warthin tumor. Intervention: RCC and Warthin tumor of the patient were surgically treated, followed by 2 cycles (14 days per cycle) of Epirubicin 40 mg day 1, Bleomycin 8 mg day 1, Vincristine 2 mg day 1, and Dacarbazine 500 mg day 1. The chemotherapy protocol was then changed to Epirubicin 40 mg day 1, Vincristine 2 mg day 1, and Dacarbazine 500 mg day 1 for 7 cycles. Outcomes: After the last day of chemotherapy, the patient showed a complete response. Lessons: To the best of our knowledge, this paper is the first to report a case of multiple primary tumors with a complete response. For their early detection, favorable prognosis, and correlation identification, we suggest a transitive relation between these coexisting tumors. Therefore, similar studies should be conducted. PMID:29642151

ONC201 induces cell death in pediatric non-Hodgkin's lymphoma cells

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Talekar, Mala K; Allen, Joshua E; Dicker, David T; El-Deiry, Wafik S

2015-01-01

ONC201/TIC10 is a small molecule initially discovered by its ability to coordinately induce and activate the TRAIL pathway selectively in tumor cells and has recently entered clinical trials in adult advanced cancers. The anti-tumor activity of ONC201 has previously been demonstrated in several preclinical models of cancer, including refractory solid tumors and a transgenic lymphoma mouse model. Based on the need for new safe and effective therapies in pediatric non-Hodgkin's lymphoma (NHL) a...

Introduction of OX40 ligand into lymphoma cells elicits anti-lymphoma immunity in vivo.

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Kaneko, Hitomi; Hori, Toshiyuki; Yanagita, Soshi; Kadowaki, Norimitsu; Uchiyama, Takashi

2005-03-01

OX40, a member of the TNF receptor superfamily, and its ligand (OX40L) play crucial roles in induction and maintenance of integrated T cell immune response. Engagement of OX40L delivers a costimulatory signal to T cells. In this study, we investigated whether inoculation of OX40L-transfected EL4, a murine T cell lymphoma cell line, could induce anti-lymphoma immunity in mice. Female C57BL/6 mice were inoculated with 1 x 10(5) cells of parental EL4, OX40L-transfected EL4 (EL4-OX40L), or mock control vector-transfected EL4 (EL4-mock), and then the tumor size, overall survival, CTL activity of spleen cells, and the immunohistochemistry were compared. While both parental EL4 and EL4-mock grew rapidly, EL4-OX40L was rejected or grew slower than parental EL4 or EL4-mock. Pretreatment of mice with either anti-CD4 or anti-CD8 mAb accelerated the growth of EL4-OX40L, suggesting that both CD4+ and CD8+ T cells were involved in anti-lymphoma immunity. The immunohistochemical study revealed the infiltration of CD8+ T cells into the tumor of EL4-OX40L. In vitro CTL assay demonstrated that spleen cells of mice that had rejected EL4-OX40L had significant cytotoxic activity against parental EL4. The gene transfer of OX40L into lymphoma cells is an eligible and efficient modality to induce anti-lymphoma immunity.

Cerebellar T-cell lymphoma: an unusual primary intracranial neoplasm

International Nuclear Information System (INIS)

Knorr, J.R.; Ragland, R.L.; Stone, B.B.; Woda, B.A.; Gelber, N.D.

1992-01-01

Primary T-cell lymphoma within the central nervous system is extremely rare. Imaging characteristics appear indistinguishable from the more common B-cell lymphoma. A case of such a primary tumor is discussed and the MRI and CT findings presented. (orig.)

Current and Emerging Therapeutics for Cutaneous T-Cell Lymphoma: Histone Deacetylase Inhibitors

OpenAIRE

Annabelle L. Rodd; Katherine Ververis; Tom C. Karagiannis

2012-01-01

Cutaneous T-cell lymphoma is a term that encompasses a spectrum of non-Hodgkin’s T-cell lymphomas with primary manifestations in the skin. It describes a heterogeneous group of neoplasms that are characterised by an accumulation of malignant T cells of the CD4 phenotype that have the propensity to home and accumulate in the skin, lymph nodes, and peripheral blood. The two most common variants of cutaneous T-cell lymphoma include mycosis fungoides and the leukemic variant, the Sézary syndrome....

Low-dose radiation enhances therapeutic HPV DNA vaccination in tumor-bearing hosts.

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Tseng, Chih-Wen; Trimble, Cornelia; Zeng, Qi; Monie, Archana; Alvarez, Ronald D; Huh, Warner K; Hoory, Talia; Wang, Mei-Cheng; Hung, Chien-Fu; Wu, T-C

2009-05-01

Current therapeutic approaches to treatment of patients with bulky cervical cancer are based on conventional in situ ablative modalities including cisplatin-based chemotherapy and radiation therapy. The 5-year survival of patients with nonresectable disease is dismal. Because over 99% of squamous cervical cancer is caused by persistent infection with an oncogenic strain of human papillomavirus (HPV), particularly type 16 and viral oncoproteins E6 and E7 are functionally required for disease initiation and persistence, HPV-targeted immune strategies present a compelling opportunity in which to demonstrate proof of principle. Sublethal doses of radiation and chemotherapeutic agents have been shown to have synergistic effect in combination with either vaccination against cancer-specific antigens, or with passive transfer of tumor-specific cytotoxic T lymphocytes (CTLs). Here, we explored the combination of low-dose radiation therapy with DNA vaccination with calreticulin (CRT) linked to the mutated form of HPV-16 E7 antigen (E7(detox)), CRT/E7(detox) in the treatment of E7-expressing TC-1 tumors. We observed that TC-1 tumor-bearing mice treated with radiotherapy combined with CRT/E7(detox) DNA vaccination generated significant therapeutic antitumor effects and the highest frequency of E7-specific CD8(+) T cells in the tumors and spleens of treated mice. Furthermore, treatment with radiotherapy was shown to render the TC-1 tumor cells more susceptible to lysis by E7-specific CTLs. In addition, we observed that treatment with radiotherapy during the second DNA vaccination generated the highest frequency of E7-specific CD8(+) T cells in the tumors and spleens of TC-1 tumor-bearing mice. Finally, TC-1 tumor-bearing mice treated with the chemotherapy in combination with radiation and CRT/E7(detox) DNA vaccination generate significantly enhanced therapeutic antitumor effects. The clinical implications of the study are discussed.

Notch 1 as a potential therapeutic target in cutaneous T-cell lymphoma

DEFF Research Database (Denmark)

Kamstrup, Maria Rørbæk; Gjerdrum, Lise Mette Rahbek; Biskup, Edyta Urszula

2010-01-01

Deregulation of Notch signaling has been linked to the development of T-cell leukemias and several solid malignancies. Yet, it is unknown whether Notch signalling is involved in the pathogenesis of mycosis fungoides and Sezary syndrome, the most common subtypes of cutaneous T cell lymphoma....... By immunohistochemistry of 40 biopsies taken from skin lesions of mycosis fungoides and Sezary syndrome we demonstrated prominent expression of Notch1 on tumor cells, especially in the more advanced stages. The gamma-secretase inhibitor I blocked Notch signaling and potently induced apoptosis in cell lines derived from...... mycosis fungoides (MyLa) and Sezary syndrome (SeAx, HuT-78)and in primary leukemic Sézary cells. Specific downregulation of Notch1 (but not Notch2 and Notch3) by siRNA induced apoptosis in SeAx. The mechanism of apoptosis involved the inhibition of NF-kappaB, which is the most important prosurvival...

Phase I clinical, pharmacokinetic, and pharmacodynamic study of KOS-862 (Epothilone D) in patients with advanced solid tumors and lymphoma.

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Konner, Jason; Grisham, Rachel N; Park, Jae; O'Connor, Owen A; Cropp, Gillian; Johnson, Robert; Hannah, Alison L; Hensley, Martee L; Sabbatini, Paul; Mironov, Svetlana; Miranov, Svetlana; Danishefsky, Samuel; Hyman, David; Spriggs, David R; Dupont, Jakob; Aghajanian, Carol

2012-12-01

To determine the maximum tolerated dose and safety of the epothilone, KOS-862, in patients with advanced solid tumors or lymphoma. Patients were treated weekly for 3 out of 4 weeks (Schedule A) or 2 out of 3 weeks (Schedule B) with KOS-862 (16-120 mg/m(2)). Pharmacokinetic (PK) sampling was performed during cycles 1 and 2; pharmacodynamic (PD) assessment for microtubule bundle formation (MTBF) was performed after the 1st dose, only at or above 100 mg/m(2). Thirty-two patients were enrolled, and twenty-nine completed ≥1 cycle of therapy. Dose limiting toxicity [DLT] was observed at 120 mg/m(2). PK data were linear from 16 to 100 mg/m(2), with proportional increases in mean C(max) and AUC(tot) as a function of dose. Full PK analysis (mean ± SD) at 100 mg/m(2) revealed the following: half-life (t (½)) = 9.1 ± 2.2 h; volume of distribution (V(z)) = 119 ± 41 L/m(2); clearance (CL) = 9.3 ± 3.2 L/h/m(2). MTBF (n = 9) was seen in 40% of PBMCs within 1 h and in 15% of PBMC at 24-hours post infusion at 100 mg/m(2). Tumor shrinkage (n = 2, lymphoma), stable disease >3 months (n = 5, renal, prostate, oropharynx, cholangiocarcinoma, and Hodgkin lymphoma), and tumor marker reductions (n = 1, colorectal cancer/CEA) were observed. KOS-862 was well tolerated with manageable toxicity, favorable PK profile, and the suggestion of clinical activity. The maximum tolerated dose was determined to be 100 mg/m(2) weekly 3-on/1-off. MTBF can be demonstrated in PBMCs of patients exposed to KOS-862.

Lung carcinoma mimicking malignant lymphoma: report of three cases.

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Matsui, K; Kitagawa, M; Wakaki, K; Masuda, S

1993-10-01

Three cases of lung carcinomas with unusual histologic appearances that have received little or no comment in the literature are presented. They were initially confused with malignant lymphoma because of a diffuse proliferation of relatively monotonous cells simulating large-cell immunoblastic lymphoma. In each case, the possibility of malignant lymphoma was excluded with confidence after the immunohistochemical study (leucocyte common antigen negative and cytokeratins positive), although with conventional microscopy several foci of cohesive groups of tumor cells were observed. The tumors were ranked at the clinical stage II or III when they were initially discovered, but all patients died of disease within 1 year. The present three tumors show an aggressive behavior and could be classified into a peculiar variant of 'large cell' carcinoma. It is necessary for surgical pathologists to have an idea of these variants of lung carcinoma in order to avoid erroneous diagnosis.

Proteomic characterization of EL4 lymphoma-derived tumors upon chemotherapy treatment reveals potential roles for lysosomes and caspase-6 during tumor cell death in vivo.

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Kramer, David A; Eldeeb, Mohamed A; Wuest, Melinda; Mercer, John; Fahlman, Richard P

2017-06-01

The murine mouse lymphoblastic lymphoma cell line (EL4) tumor model is an established in vivo apoptosis model for the investigation of novel cancer imaging agents and immunological treatments due to the rapid and significant response of the EL4 tumors to cyclophosphamide and etoposide combination chemotherapy. Despite the utility of this model system in cancer research, little is known regarding the molecular details of in vivo tumor cell death. Here, we report the first in-depth quantitative proteomic analysis of the changes that occur in these tumors upon cyclophosphamide and etoposide treatment in vivo. Using a label-free quantitative proteomic approach a total of 5838 proteins were identified in the treated and untreated tumors, of which 875 were determined to change in abundance with statistical significance. Initial analysis of the data reveals changes that may have been predicted, such as the downregulation of ribosomes, but demonstrates the robustness of the dataset. Analysis of the dataset also reveals the unexpected downregulation of caspase-3 and an upregulation of caspase-6 in addition to a global upregulation of lysosomal proteins in the bulk of the tumor. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Heart of Lymphoma: Primary Mediastinal Large B-Cell Lymphoma with Endomyocardial Involvement

Directory of Open Access Journals (Sweden)

Elisa Rogowitz

2013-01-01

Full Text Available Primary mediastinal B-cell lymphoma (PMBCL is an uncommon aggressive subset of diffuse large B-cell lymphomas. Although PMBCL frequently spreads locally from the thymus into the pleura or pericardium, it rarely invades directly through the heart. Herein, we report a case of a young Mexican female diagnosed with PMBCL with clear infiltration of lymphoma through the cardiac wall and into the right atrium and tricuspid valve leading to tricuspid regurgitation. This was demonstrated by cardiac MRI and transthoracic echocardiogram. In addition, cardiac MRI and CT scan of the chest revealed the large mediastinal mass completely surrounding and eroding into the superior vena cava (SVC wall causing a collar of stokes. The cardiac and SVC infiltration created a significant therapeutic challenge as lymphomas are very responsive to chemotherapy, and treatment could potentially lead to vascular wall rupture and hemorrhage. Despite the lack of conclusive data on chemotherapy-induced hemodynamic compromise in such scenarios, her progressive severe SVC syndrome and respiratory distress necessitated urgent intervention. In addition to the unique presentation of this rare lymphoma, our case report highlights the safety of R-CHOP treatment.

Metallothionein as a useful marker in Hodgkin lymphoma subclassification

DEFF Research Database (Denmark)

Penkowa, Milena; Sørensen, Brit Ladegaard; Nielsen, Signe Lidou

2009-01-01

Metallothionein (MT) expression is considered to be a prognostic factor that promotes tumor resistance to apoptosis. In non-Hodgkin lymphomas, MT is differentially expressed and constitutes a risk factor. We have characterised MT in lymph nodes of Hodgkin lymphoma (HL) [patients with nodular...

Therapeutic strategy with artificially-designed i-lncRNA targeting multiple oncogenic microRNAs exhibits effective antitumor activity in diffuse large B-cell lymphoma.

Science.gov (United States)

Su, Yinghan; Sun, Bin; Lin, Xuejing; Zhao, Xinying; Ji, Weidan; He, Miaoxia; Qian, Haihua; Song, Xianmin; Yang, Jianmin; Wang, Jianmin; Chen, Jie

2016-08-02

In diffuse large B-cell lymphoma (DLBCL), many oncogenic microRNAs (OncomiRs) are highly expressed to promote disease development and progression by inhibiting the expression and function of certain tumor suppressor genes, and these OncomiRs comprise a promising new class of molecular targets for the treatment of DLBCL. However, most current therapeutic studies have focused on a single miRNA, with limited treatment outcomes. In this study, we generated tandem sequences of 10 copies of the complementary binding sequences to 13 OncomiRs and synthesized an interfering long non-coding RNA (i-lncRNA). The highly-expressed i-lncRNA in DLBCL cells would compete with the corresponding mRNAs of OncomiR target genes for binding OncomiRs, thereby effectively consuming a large amount of OncomiRs and protecting many tumor suppressor genes. The in vitro experiments confirmed that the i-lncRNA expression significantly inhibited cell proliferation, induced cell cycle arrest and apoptosis in DLBCL cell lines, mainly through upregulating the expression of PTEN, p27kip1, TIMP3, RECK and downregulating the expression of p38/MAPK, survivin, CDK4, c-myc. In the established SUDHL-4 xenografts in nude mice, the treatment strategy involving adenovirus-mediated i-lncRNA expression significantly inhibited the growth of DLBCL xenografts. Therefore, this treatment would specifically target the carcinogenic effects of many OncomiRs that are usually expressed in DLBCL and not in normal cells, such a strategy could improve anti-tumor efficacy and safety and may be a good prospect for clinical applications.

Blood Outgrowth Endothelial Cells Increase Tumor Growth Rates and Modify Tumor Physiology: Relevance for Therapeutic Targeting

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Pagan, Jonathan, E-mail: jdpagan@uams.edu; Przybyla, Beata; Jamshidi-Parsian, Azemat [Department of Radiation Oncology, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205 (United States); Gupta, Kalpna [Vascular Biology Center and Division of Hematology-Oncology Transplantation, Department of Medicine, University of Minnesota Medical School, MN 72223 (United States); Griffin, Robert J. [Department of Radiation Oncology, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205 (United States)

2013-02-18

Endothelial cell precursors from human peripheral blood have been shown to home to areas of neovascularization and may assist tumor growth by increasing or fortifying blood vessel growth. In the present study, the influence of these cells on tumor growth and physiology was investigated and the role of these cells as a therapeutic target or in determining treatment sensitivity was tested. After isolation from human blood and expansion in vitro, actively growing cells with verified endothelial phenotype (Blood Outgrowth Endothelial Cell, BOEC) were injected i.v. into tumor bearing mice for three consecutive days. The growth rate was significantly enhanced in relatively small RERF human lung tumors (i.e., less than 150 mm{sup 3}) grown in immunocompromised mice by an average of 1.5-fold while it had no effect when injections were given to animals bearing larger tumors. There were no signs of toxicity or unwanted systemic effects. We also observed evidence of increased perfusion, vessel number, response to 15 Gy radiation and oxygenation in RERF tumors of animals injected with BOECs compared to control tumors. In addition, FSaII murine fibrosarcoma tumors were found to grow faster upon injection of BOECs. When FSaII tumors were subjected to a partial thermal ablation treatment using high intensity focused ultrasound (HIFU) there was consistently elevated detection of fluorescently labeled and i.v. injected endothelial precursors in the tumor when analyzed with optical imaging and/or histological preparations. Importantly, we also observed that BOECs treated with the novel anti-angiogenic peptide anginex in-vitro, show decreased proliferation and increased sensitivity to radiation. In vivo, the normal increase in FSaII tumor growth induced by injected BOECs was blunted by the addition of anginex treatment. It appears that endothelial precursors may significantly contribute to tumor vessel growth, tumor progression and/or repair of tumor damage and may improve the

Blood Outgrowth Endothelial Cells Increase Tumor Growth Rates and Modify Tumor Physiology: Relevance for Therapeutic Targeting

International Nuclear Information System (INIS)

Pagan, Jonathan; Przybyla, Beata; Jamshidi-Parsian, Azemat; Gupta, Kalpna; Griffin, Robert J.

2013-01-01

Endothelial cell precursors from human peripheral blood have been shown to home to areas of neovascularization and may assist tumor growth by increasing or fortifying blood vessel growth. In the present study, the influence of these cells on tumor growth and physiology was investigated and the role of these cells as a therapeutic target or in determining treatment sensitivity was tested. After isolation from human blood and expansion in vitro, actively growing cells with verified endothelial phenotype (Blood Outgrowth Endothelial Cell, BOEC) were injected i.v. into tumor bearing mice for three consecutive days. The growth rate was significantly enhanced in relatively small RERF human lung tumors (i.e., less than 150 mm 3 ) grown in immunocompromised mice by an average of 1.5-fold while it had no effect when injections were given to animals bearing larger tumors. There were no signs of toxicity or unwanted systemic effects. We also observed evidence of increased perfusion, vessel number, response to 15 Gy radiation and oxygenation in RERF tumors of animals injected with BOECs compared to control tumors. In addition, FSaII murine fibrosarcoma tumors were found to grow faster upon injection of BOECs. When FSaII tumors were subjected to a partial thermal ablation treatment using high intensity focused ultrasound (HIFU) there was consistently elevated detection of fluorescently labeled and i.v. injected endothelial precursors in the tumor when analyzed with optical imaging and/or histological preparations. Importantly, we also observed that BOECs treated with the novel anti-angiogenic peptide anginex in-vitro, show decreased proliferation and increased sensitivity to radiation. In vivo, the normal increase in FSaII tumor growth induced by injected BOECs was blunted by the addition of anginex treatment. It appears that endothelial precursors may significantly contribute to tumor vessel growth, tumor progression and/or repair of tumor damage and may improve the

Curative radiotherapy for primary orbital lymphoma

International Nuclear Information System (INIS)

Bhatia, Sudershan; Paulino, Arnold C.; Buatti, John M.; Mayr, Nina A.; Wen, B.-C.

2002-01-01

Purpose: To review our institutional experience with primary orbital lymphoma and determine the prognostic factors for survival, local control, and distant metastases. In addition, we also analyzed the risk factors for complications in the radiotherapeutic management of this tumor. Methods and Materials: Between 1973 and 1998, 47 patients (29 women [62%] and 18 men [38%], median age 69 years, range 32-89) with Stage IAE orbital lymphoma were treated with curative intent at one department. Five had bilateral orbital involvement. The tumor was located in the eyelid and extraocular muscles in 23 (44%), conjunctiva in 17 (33%), and lacrimal apparatus in 12 (23%). The histologic features according to the World Heath Organization classification of lymphoid neoplasms was follicular lymphoma in 25, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type in 8, diffuse large B-cell lymphoma in 12, mantle cell lymphoma in 6, and peripheral T-cell lymphoma in 1. For the purposes of comparison with the existing literature on orbital lymphomas, the grading system according to the Working Formulation was also recorded. The histologic grade was low in 33 (63%), intermediate in 18 (35%), and high in 1 (2%). All patients were treated with primary radiotherapy alone. The median dose for low-grade tumors was 3000 cGy (range 2000-4020); the median dose for intermediate and high-grade tumors was 4000 cGy (range 3000-5100). A lens-sparing approach was used in 19 patients (37%). Late complications for the lens and cornea were scored according to the subjective, objective, management, and analytic (SOMA) scale of the Late Effects of Normal Tissue (LENT) scoring system. The median follow-up was 55 months (range 6-232). Results: The local control rate was 100% in the 52 orbits treated. The 5-year overall survival and relapse-free survival rate was 73.6% and 65.5%, respectively. Tumor grade and location did not predict for overall survival or relapse-free survival

Radioimmunotherapy of non-Hodgkin lymphoma

International Nuclear Information System (INIS)

Batista Cuellar, Juan F.

2016-01-01

Non-Hodgkin lymphoma have a worse prognosis compared with other varieties of lymphoma and conventional therapy has specific onco higher incidence of unsatisfactory answers becoming more frequent recurrences of the disease. Radioimmunotherapy has proven to be an effective adjuvant therapy often in cases where conventional therapy this not proving effective. In this paper an exhibition of the current international state of the therapeutic and experiences and possibilities that exist in our environment to develop their use is done. (author)

Clinical roundtable monograph: CD30 in lymphoma: its role in biology, diagnostic testing, and targeted therapy.

Science.gov (United States)

Sotomayor, Eduardo M; Young, Ken H; Younes, Anas

2014-04-01

CD30, a member of the tumor necrosis factor receptor superfamily, is a transmembrane glycoprotein receptor consisting of an extracellular domain, a transmembrane domain, and an intracellular domain. CD30 has emerged as an important molecule in the field of targeted therapy because its expression is generally restricted to specific disease types and states. The major cancers with elevated CD30 expression include Hodgkin lymphoma and anaplastic large T-cell lymphoma, and CD30 expression is considered essential to the differential diagnosis of these malignancies. Most commonly, CD30 expression is detected and performed by immunohistochemical staining of biopsy samples. Alternatively, flow cytometry analysis has also been developed for fresh tissue and cell aspiration specimens, including peripheral blood and bone marrow aspirate. Over the past several years, several therapeutic agents were developed to target CD30, with varying success in clinical trials. A major advance in the targeting of CD30 was seen with the development of the antibody-drug conjugate brentuximab vedotin, which consists of the naked anti-CD30 antibody SGN-30 conjugated to the synthetic antitubulin agent monomethyl auristatin E. In 2011, brentuximab vedotin was approved by the US Food and Drug Administration for use in Hodgkin lymphoma and anaplastic large cell lymphoma based on clinical trial data showing high response rates in these indications. Ongoing trials are examining brentuximab vedotin after autologous stem cell transplantation, as part of chemotherapy combination regimens, and in other CD30-expressing malignancies, including primary mediastinal large B-cell lymphomas, diffuse large B-cell lymphoma, lymphoma positive for Epstein-Barr virus, peripheral T-cell lymphoma not otherwise specified, and cutaneous anaplastic large cell lymphoma.

Nasal non-hodgkin's lymphoma : CT findings

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No, Tae Youn; Baek, Ho Gil; Won, Jong Bu; Park, Sung Ho; Park, O Bong; Baik, Seung Kug; Shin, Mi Jung; Kim, Bong Ki; Choi, Han Yong [Wallace Memorial Baptist Hospital, Pusan (Korea, Republic of)

1997-05-01

To describe the characteristics of CT findings in nasal lymphoma. We retrospectively reviewed CT findings and pathologic findings of eight patients (six males and two females) aged between 24 and 68 years with pathologically-proven nasal lymphoma. We analyzed mass location, laterality, size, margin, mass effect, adjacent bony change and contrast enhancement pattern. All eight cases were non-Hodgkin's lymphoma, intermediate grade, diffuse large cell type. Seven cases were B-cell type and one was T-cell. In all cases, tumors were located in the medial wall of the inferior turbinate. In four cases, they were also found in the anterior ethmoidal sinus, and in one case, in the nasal septum. The mean size of the main mass was 3.3cm. In seven cases, tumors were unilateral (one on the right; six on the left), and in the remaining case, bilateral. In six cases tumor margin was smooth and in two cases focal nodularity was seen. In two cases there was no bony change, and in four, there was mucosal thickening along the nasal septum; in one of these four, minimal bony erosion was also found. In the other two cases, bony destruction was seen, and tumors were very large(7cm in diameter) or bilterally located. In three cases, the nasal septum was displaced by the mass. In all cases with bony change, the nasal septum was involved. All tumors were homogeneously well enhanced after IV contrast administration. The main CT findings of nasal non-Hodgkin's lymphoma were smooth margin, unilateral location (mainly in the medial wall of the inferior turbinate and growing to the medial side without bony destruction) mucosal thickening along the nasal septum and clear homogeneous enhancement after IV contrast administration. These characteristics will help diagnosis, help deter-mine the appropriate region for radiation and other appropriate therapy, and facilitate prognosis in patients with nasal non-Hodgkin's lymphoma.

Medicinal therapy of malignant lymphomas

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Aul, C.; Schroeder, M.; Giagounidis, A.

2002-01-01

Chemotherapy represents the most important therapeutic option in malignant lymphomas. Low to intermediate risk Hodgkin's disease is treated by a combination of chemotherapy and radiation. The new chemotherapy protocol BEACOPP has improved the outcome of advanced stages in comparison with the internationally accepted standard protocol COPP/ABVD. Dependent on the initial staging, cure rates between 50 and 95% can be achieved. Indolent non-Hodgkin's lymphomas usually present in advanced stages of disease. Chemotherapy in these cases has palliative character and aims at improving patients'quality of life and at avoiding complications due to the disease. In aggressive and very aggressive non-Hodgkin's lymphoma chemotherapy is curative and must be initiated immediately irrespective of the staging results. The efficacy of the standard protocol CHOP (cyclophosphamide,doxorubicin, vincristine and prednisone), that was established in the 1970s, has recently been improved by shortening of the therapy interval (CHOP-14 vs.CHOP-21),addition of etoposide (CHOEP) and combination with the monoclonal antibody rituximab (R-CHOP). The value of high dose chemotherapy with stem cell transplantation has been shown unequivocally only for aggressive non-Hodgkin lymphoma and relapsed Hodgkin's disease responsive to chemotherapy. The therapeutic strategy of malignant lymphomas is likely to be improved within the next years due to the introduction of novel cytostatic agents, the broadening application of monoclonal antibodies,upcoming new transplantation procedures and the development of substances with molecular targets.To rapidly increase our current knowledge on the topic it is mandatory to include patients into the large national and international multicenter studies. (orig.) [de

Prognostic value of flow cytometry in surgically treated primary gastric lymphoma Valor pronóstico de la citometría de flujo en el linfoma gástrico

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F. Fernández

2006-11-01

Full Text Available Aim: to investigate whether flow cytometry could help to define the optimal therapeutic strategy of primary gastric lymphomas. Material and method: retrospective study of 46 patients having primary gastric lymphoma -according to Dawson criteria- in Ann Arbor stage I E and II E, who were surgically treated. From selected paraffin-embedded tissue blocks of the tumor, DNA content was studied by flow cytometry (FC. Other pathological tumor features were analysed by hematoxiline-eosine and Giemsa stains as well as immunohistochemical study; any possible influence on postoperative survival was investigated through statistical analysis. Results: the DNA ploidy pattern was diploid in 40 cases (87% and aneuploid (hyperdiploid in 6 (13%. Postoperative survival probability (PSP was 62.7% at 5 years. Statistical analysis showed significant prognostic value for Ann Arbor classification -with higher PSP for stage I E (p = 0.009- and FC parameters: diploid tumors had higher PSP than aneuploid tumors. Also tumors having S-phase (p = 0.044 or G2-M phase values (p = 0.023 under the respective mean values had higher PSP. No influence on PSP was found for wall invasion, Helicobacter pylori infection, Isaacson's histologic type or resection margin involvement. No significant relationship was appreciated between Isaacson's histologic type and DNA ploidy patterns. Conclusion: FC could be useful in assessing gastric lymphoma prognosis.

Classification of malignant lymphomas

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Schneider, M.; Thyss, A.

1986-01-01

Malignant lymphomas, primary tumors of the lymphoid tissues, were first described in 1832 by Thomas Hodgkin. The histological characteristics were later defined by Sternberg and Reed, and Virchow introduced the concept of lymphosarcoma in 1863. Today, these pathologies are grouped together under the synonymous terms hematosarcoma or malignant lymphoma, which are in turn divided into Hodgkin's disease (HD) and non-Hodgkin's malignant lymphomas (NHL). The therapy of lymphomas is controversial. The validity of treatment for asymptomatic patients is questioned, owing to the indolent course of many lymphomas. Results for histologically unfavorable forms are highly disparate. Exclusive radiotherapy has occasionally produced up to 78% disease-free survival at 5 years for truly localized stages. Today, however, use of chemotherapy/radiotherapy combinations is almost universal, with chemotherapy occasionally being used alone and providing 90% disease-free survival at 5 years. Chemotherapy is the main treatment for disseminated forms; the major associations include doxorubicin hydrochloride (Adriamycin), cyclophosphamide, vincristine sulfate, methotrexate, and prednisone. Radiotherapy is used more for adjuvant purposes. Synthesis of recent studies allows us to reasonably expect 40% relapse-free survival at 10 years and the establishment of a cure plateau in the near future

iNKT cells suppress the CD8+ T cell response to a murine Burkitt's-like B cell lymphoma.

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Ryan L Bjordahl

Full Text Available The T cell response to B cell lymphomas differs from the majority of solid tumors in that the malignant cells themselves are derived from B lymphocytes, key players in immune response. B cell lymphomas are therefore well situated to manipulate their surrounding microenvironment to enhance tumor growth and minimize anti-tumor T cell responses. We analyzed the effect of T cells on the growth of a transplantable B cell lymphoma and found that iNKT cells suppressed the anti-tumor CD8(+ T cell response. Lymphoma cells transplanted into syngeneic wild type (WT mice or Jalpha18(-/- mice that specifically lack iNKT cells grew initially at the same rate, but only the mice lacking iNKT cells were able to reject the lymphoma. This effect was due to the enhanced activity of tumor-specific CD8(+ T cells in the absence of iNKT cells, and could be partially reversed by reconstitution of iNKT cells in Jalpha 18(-/- mice. Treatment of tumor-bearing WT mice with alpha -galactosyl ceramide, an activating ligand for iNKT cells, reduced the number of tumor-specific CD8(+ T cells. In contrast, lymphoma growth in CD1d1(-/- mice that lack both iNKT and type II NKT cells was similar to that in WT mice, suggesting that type II NKT cells are required for full activation of the anti-tumor immune response. This study reveals a tumor-promoting role for iNKT cells and suggests their capacity to inhibit the CD8(+ T cell response to B cell lymphoma by opposing the effects of type II NKT cells.

Studies on a transplantable C57BL/6 mouse lymphoma

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Kendall, C.E.

1977-01-01

A C57BL/6 mouse lymphoma was demonstrated to be of T cell origin by treating the lymphoma cells with anti-Thy 1.2 antisera in a complement-dependent cytotoxicity test. The lymphoma's growth pattern was described using flow microfluorometric determinations and spleen weight progression. C-type particles were identified in electron micrographs of the lymphoma. C57BL/6 mice were immunized against the lymphoma by injecting x-ray inactivated lymphoma cells into the mice. Protection of immunized mice against live lymphoma cells demonstrated tumor antigens on the lymphoma cells. The success of immunization was found to depend on: route of injection, antigen dosage, state of the antigen, number of injections and the vaccination-challenge interval. Attempts were made to passively transfer immunity from immunized C57BL/6 mice which had survived lymphoma challenge to non-treated, syngeneic mice. The route of immunization in the donors influenced the success of passively transferred immunity in the recipients. Serum from days 1 to 3 and days 11 to death (day 17) had an enhancing effect on lymphoma growth. However, sera from days 5 to 9 retarded lymphoma growth. The C57BL/6 lymphoma cells were injected into rabbits and other strains of mice to demonstrate tumor specificity. The lymphoma did not grow in rabbits and only grew in one mouse strain. This strain had the same major histocompatibility loci as C57BL/6 mice. Crosses were made between C57BL/6 mice and a resistant strain of mice (DBA/2 mice). The F 1 hybrids were found to be less susceptible to the lymphoma than the C57BL/6 strain. Sublethal x-irradiation of the F 1 mice decreased its ability to resist the C57BL/6 lymphoma. Immunization with x-ray inactivated C57BL/6 lymphoma cells increased survival after challenge with lymphoma in the F 1 mice

Gastric mucosa-associated lymphoid tissue lymphomas and Helicobacter pylori infection: A Colombian perspective

Institute of Scientific and Technical Information of China (English)

Sally Yepes; Maria Mercedes Torres; Carlos Saavedra; Rafael Andrade

2012-01-01

AIM:To assess the significance of chromosome translocation t(11;18)(q21;q21),B-cell lymphoma 10 (BCL-10)protein and Helicobacter pylori (H.pylori) infection in gastric mucosa-associated lymphoid tissue (MALT) lymphoma in Colombia.METHODS:Fifty cases of gastric MALT lymphoma and their respective post-treatment follow-up biopsies were examined to assess the presence of the translocation t(11;18)(q21;q21) as identified by fluorescence in situ hybridization; to detect protein expression patterns of BCL10 using immunohistochemistry; and for evaluation of tumor histology to determine the correlation of these factors and resistance to H.pylori eradication.RESULTS:Infection with H.pylori was confirmed in all cases of gastric MALT lymphoma in association with chronic gastritis.Bacterial eradication led to tumor regression in 66％ of cases.The translocation t(11;18)(q21;q21) was not present in any of these cases,nor was there evidence of tumor transformation to diffuse large B-cell lymphoma.Thirty-four percent of the patients showed resistance to tumor regression,and within this group,7 cases,representing 14％ of all those analyzed,were considered to be t(11;18)(q21;q21)-positive gastric MALT lymphomas.Protein expression of BCL10 in the nucleus was associated with the presence of translocation and treatment resistance.Cases that were considered unresponsive to therapy were histologically characterized by the presence of homogeneous tumor cells and a lack of plasmacytic differentiation.Responder cases exhibited higher cellular heterogeneity and a greater frequency of plasma cells.CONCLUSION:Both t(11;18)(q21;q21)-positive MALT lymphoma cases and those with nuclear BCL10 expression are considered resistant to H,pylori eradication.It is suggested that chronic antigenic stimulation is not a dominant event in resistant cases.

Case studies of elderly patients with non-Hodgkin's lymphoma

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Stefano Luminari

2011-10-01

Full Text Available The treatment of patients with non- Hodgkin’s lymphoma (NHL is often the treatment of elderly patients, as most patients are older than 65 years at diagnosis. These elderly patients present particular therapeutic challenges, because they may be more frail and at greater risk of treatment-related toxicity, especially anthracycline-related cardiotoxicity, than younger patients. The following two case studies illustrate the challenges and therapeutic decision-making in managing elderly patients with an aggressive and an indolent form of lymphoma.

Evaluation of radioiodinated curcumin for its potential as a tumor-targeting radiopharmaceutical

International Nuclear Information System (INIS)

Kumar, Chandan; Subramanian, Suresh; Samuel, Grace

2016-01-01

Curcumin, a component of the spice turmeric has widely reported anticancer properties in several types of cancer. The differential accumulation and mechanism of its action in normal and cancer cells have proven its potential in targeting tumor. Therefore, it was of interest to label curcumin with a suitable radionuclide and explore its potential for use in nuclear medicine. Curcumin was labeled with "1"2"5I by iodogen method. The radiochemical purity was analyzed by paper electrophoresis and high-performance liquid chromatography (HPLC) method. Cell binding was carried out in murine lymphoma and melanoma cell lines. Bioevaluation and pharmacokinetics of radioiodinated curcumin was carried out in lymphoma-bearing mice for various time points (1, 3, 24, and 48 h). The efficiency of labeling was >75% and the radiochemical purity postpurification was >95%. The maximum uptake (∼7% at 2 h, 37°C using 5 X 10"5 cells) was observed in EL4 cells. Significant tumor uptake in lymphoma-bearing mice was observed at 180 min (3.3 ± 0.76% ID/g). In addition, pharmacokinetics of radioiodinated curcumin is fast, with the majority of the preparation out of the bloodstream in 3 h. The results of these studies suggest that curcumin has the potential for targeting lymphomas, which may be used as diagnostic/therapeutic agent by labeling with other radionuclides. (author)

Tumors and Pregnancy

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Tumors during pregnancy are rare, but they can happen. Tumors can be either benign or malignant. Benign tumors aren't cancer. Malignant ones are. The most common cancers in pregnancy are breast cancer, cervical cancer, lymphoma, and melanoma. ...

Splenic marginal zone lymphoma: from genetics to management.

Science.gov (United States)

Arcaini, Luca; Rossi, Davide; Paulli, Marco

2016-04-28

Splenic marginal zone lymphoma (SMZL) is a rare B-cell malignancy involving the spleen, bone marrow, and frequently the blood. SMZL lymphomagenesis involves antigen and/or superantigen stimulation and molecular deregulation of genes (NOTCH2 and KLF2) involved in the physiological differentiation of spleen marginal zone B cells. Diagnosis requires either spleen histology or, alternatively, the documentation of a typical cell morphology and immunophenotype on blood cells coupled with the detection of intrasinusoidal infiltration by CD20(+) cells in the bone marrow. Among B-cell tumors, deletion of 7q and NOTCH2 mutations are almost specific lesions of SMZL, thus representing promising diagnostic biomarkers of this lymphoma. Although the majority of SMZLs show an indolent course with a median survival of approximately 10 years, nearly 30% of patients experience a poor outcome. No randomized trials are reported for SMZL, and few prospective trials are available. A watch-and-wait approach is advisable for asymptomatic patients. Treatment options for symptomatic patients ranges from splenectomy to rituximab alone or combined with chemotherapy. In some geographic areas, a subset of patients with SMZL associates with hepatitis C virus infection, prompting virus eradication as an effective lymphoma treatment. It would be worthwhile to explore deregulated cellular programs of SMZL as therapeutic targets in the future; improved clinical and biological prognostication will be essential for identifying patients who may benefit from novel approaches. © 2016 by The American Society of Hematology.

FDG-PET in Follicular Lymphoma Management

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C. Bodet-Milin

2012-01-01

Full Text Available 18-Fluoro-deoxyglucose positron emission tomography/computerised tomography (FDG PET/CT is commonly used in the management of patients with lymphomas and is recommended for both initial staging and response assessment after treatment in patients with diffuse large B-cell lymphoma and Hodgkin lymphoma. Despite the FDG avidity of follicular lymphoma (FL, FDG PET/CT is not yet applied in standard clinical practice for patients with FL. However, FDG PET/CT is more accurate than conventional imaging for initial staging, often prompting significant management change, and allows noninvasive characterization to guide assessment of high-grade transformation. For restaging, FDG PET/CT assists in distinguishing between scar tissue and viable tumors in residual masses and a positive PET after induction treatment would seem to predict a shorter progression-free survival.

Targeted radionuclide therapy for solid tumors: An overview

International Nuclear Information System (INIS)

De Nardo, Sally J.; De Nardo, Gerald L.

2006-01-01

Although radioimmunotherapy (RIT) has been effective in non-Hodgkin's lymphoma (NHL) as a single agent, solid tumors have shown less clinically significant therapeutic response to RIT alone. The clinical impact of RIT or other forms of targeted radionuclide therapy for solid tumors depends on the development of a high therapeutic index (TI) for the tumor vs. normal tissue effect, and the implementation of RIT as part of synergistic combined modality therapy (CMRIT). Preclinical and clinical studies have provided a wealth of information, and new prototypes or paradigms have shed light on future possibilities in many instances. Evidence suggests that combination and sequencing of RIT in CMRIT appropriately can provide effective treatment for many solid tumors. Vascular targets provide RIT enhancement opportunities and nanoparticles may prove to be effective carriers for RIT combined with intracellular drug delivery or alternating magnetic frequency (AMF) induced thermal tumor necrosis. The sequence and timing of combined modality treatments will be of critical importance to achieve synergy for therapy while minimizing toxicity. Fortunately, the radionuclide used for RIT also provides a signal useful for nondestructive quantitation of the influence of sequence and timing of CMRIT on events in animals and patients. This can be readily accomplished clinically using quantitative high-resolution imaging (e.g., positron emission tomography [PET])

Radiotherapy of primary gastric malignant lymphoma

International Nuclear Information System (INIS)

Monzen, Yoshio; Mutsukura, Masahide; Moriuchi, Yukiyoshi

2017-01-01

Fifteen patients with primary gastric malignant lymphoma who underwent radiotherapy were examined. Median age was 68 years, and male to female ratio was 1:2. All the cases were stage I including 7 cases of diffuse large B-cell lymphoma (DLBCL), 7 cases of MALT lymphoma, and 1 case of follicular lymphoma. Therapy methods were as follows. For DLBCL, 30 Gy of radiotherapy was performed after chemotherapy. For six cases of MALT lymphomas, 30 Gy of radiotherapy was performed. For one patient diagnosed as high-grade gastric MALT lymphoma was treated in the same way as DLBCL. For one patient with follicular lymphoma, 30 Gy of radiotherapy was performed. The radiotherapy was applied with 3-dimensional fixed multi-portal irradiation, with the reduced irradiation of the liver and kidney. There was no recurrence of disease in all cases, and all patients have been alive, and no-recurrence living periods are 20 to 120 months. There was no harmful adverse event, and the tumor had disappeared with 30 Gy of radiation therapy in all cases. Considering the occurrence of secondary cancer, it was considered that a dosage of more than 30 Gy was not necessary for primary gastric malignant lymphoma. (J.P.N.)

Tracheal involvement of bronchus-associated lymphoid tissue lymphoma: a case report

International Nuclear Information System (INIS)

Sohn, Kyung Sik; Jeon, Kyung Neough; Kang, Duk Sik

2002-01-01

Primary malignant tumors of the trachea are rare, the most prevalent histologies beeing squamous cell and adenoid cystic carcinoma. A review of the literature revealed only ten cases of primary tracheal or bronchial non-Hodgkin's lymphoma. We describe a case in which tracheal involvement of bronchus-associated lymphoid tissue lymphoma, a subtype of non-Hodgkin's lymphoma, occurred

Genetic analysis of radiation-induced mouse thymic lymphomas

International Nuclear Information System (INIS)

Kominami, R.; Wakabayashi, Y.; Niwa, O.

2003-01-01

Mouse thymic lymphomas are one of the classic models of radiation-induced malignancies, and the model has been used for the study of genes involved in carcinogenesis. ras oncogenes are the first isolate which undergoes mutations in 10 to 30 % of lymphomas, and p16INK4a and p19ARF in the INK4a-ARF locus are also frequently inactivated. In our previous study, the inactivation of Ikaros, a key regurator of lymphoid system, was found in those lymphomas, and it was suggested that there are other responsible genes yet to be discovered. On the other hand, genetic predisposition to radiation-induced lymphoma often differs in different strains, and this reflects the presence of low penetrance genes that can modify the impact of a given mutation. Little study of such modifiers or susceptibility genes has been performed, either. Recent availability of databases on mouse genome information and the power of mouse genetic system underline usefulness of the lymphoma model in search for novel genes involved, which may provide clues to molecular mechanisms of development of the radiogenic lymphoma and also genes involved in human lymphomas and other malignancies. Accordingly, we have carried out positional cloning for the two different types of tumor-related genes. In this symposium, our current progress is presented that includes genetic mapping of susceptibility/ resistance loci on mouse chromosomes 4, 5 and 19, and also functional analysis of a novel tumor suppressor gene, Rit1/Bcl11b, that has been isolated from allelic loss (LOH) mapping and sequence analysis for γ -ray induced mouse thymic lymphomas

Dynamic mathematical modeling of IL13-induced signaling in Hodgkin and primary mediastinal B-cell lymphoma allows prediction of therapeutic targets.

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Raia, Valentina; Schilling, Marcel; Böhm, Martin; Hahn, Bettina; Kowarsch, Andreas; Raue, Andreas; Sticht, Carsten; Bohl, Sebastian; Saile, Maria; Möller, Peter; Gretz, Norbert; Timmer, Jens; Theis, Fabian; Lehmann, Wolf-Dieter; Lichter, Peter; Klingmüller, Ursula

2011-02-01

Primary mediastinal B-cell lymphoma (PMBL) and classical Hodgkin lymphoma (cHL) share a frequent constitutive activation of JAK (Janus kinase)/STAT signaling pathway. Because of complex, nonlinear relations within the pathway, key dynamic properties remained to be identified to predict possible strategies for intervention. We report the development of dynamic pathway models based on quantitative data collected on signaling components of JAK/STAT pathway in two lymphoma-derived cell lines, MedB-1 and L1236, representative of PMBL and cHL, respectively. We show that the amounts of STAT5 and STAT6 are higher whereas those of SHP1 are lower in the two lymphoma cell lines than in normal B cells. Distinctively, L1236 cells harbor more JAK2 and less SHP1 molecules per cell than MedB-1 or control cells. In both lymphoma cell lines, we observe interleukin-13 (IL13)-induced activation of IL4 receptor α, JAK2, and STAT5, but not of STAT6. Genome-wide, 11 early and 16 sustained genes are upregulated by IL13 in both lymphoma cell lines. Specifically, the known STAT-inducible negative regulators CISH and SOCS3 are upregulated within 2 hours in MedB-1 but not in L1236 cells. On the basis of this detailed quantitative information, we established two mathematical models, MedB-1 and L1236 model, able to describe the respective experimental data. Most of the model parameters are identifiable and therefore the models are predictive. Sensitivity analysis of the model identifies six possible therapeutic targets able to reduce gene expression levels in L1236 cells and three in MedB-1. We experimentally confirm reduction in target gene expression in response to inhibition of STAT5 phosphorylation, thereby validating one of the predicted targets.

Enzymatic Inactivation of Endogenous IgG by IdeS Enhances Therapeutic Antibody Efficacy.

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Järnum, Sofia; Runström, Anna; Bockermann, Robert; Winstedt, Lena; Crispin, Max; Kjellman, Christian

2017-09-01

Endogenous plasma IgG sets an immunologic threshold that dictates the activity of tumor-directed therapeutic antibodies. Saturation of cellular antibody receptors by endogenous antibody limits antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Here, we show how enzymatic cleavage of IgG using the bacterial enzyme IdeS can be utilized to empty both high and low affinity Fcγ-receptors and clear the entire endogenous antibody pool. Using in vitro models, tumor animal models as well as ex vivo analysis of sera collected during a previous clinical trial with IdeS, we show how clearing of competing plasma antibody levels with IdeS unblocks cellular antibody receptors. We show that therapeutic antibodies against breast cancer (trastuzumab), colon cancer (cetuximab), and lymphomas (rituximab and alemtuzumab) can be potentiated when endogenous IgG is removed. Overall, IdeS is shown to be a potent tool to reboot the human antibody repertoire and to generate a window to preferentially load therapeutic antibodies onto effector cells and thereby create an armada of dedicated tumor-seeking immune cells. Mol Cancer Ther; 16(9); 1887-97. ©2017 AACR . ©2017 American Association for Cancer Research.

Protective specific immunity induced by cyclophosphamide plus tumor necrosis factor alpha combination treatment of EL4-lymphoma-bearing C57BL/6 mice.

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Krawczyk, C M; Verstovsek, S; Ujházy, P; Maccubbin, D; Ehrke, M J

1995-06-01

A combination treatment protocol initiated 12 days after tumor injection, when the tumor was large, by administering cyclophosphamide (CY, 150 or 250 mg/kg) intraperitoneally followed by intravenous tumor necrosis factor alpha (TNF alpha, 1000 units injection) on days 13, 16, 18, 21, and 23, resulted in about 60% long-term survival (i.e., survival for at least 60 days) in the syngeneic C57BL/6 mouse/EL4 lymphoma model system. The establishment of a specific antitumor immune memory and its possible therapeutic relevance was verified by reinjecting 60-day survivors with EL4 cells; all 60-day survivors that had received the combination treatments rejected the implants and survived for a further 60 days. Thymic cellularity was reduced during treatment and its recovery appeared to correlate with long-term survival and immunity. Thymocytes from mice treated with the combination were found to express significant levels of specific anti-EL4 cytolytic activity following a 4-day stimulation culture with X-irradiated EL4 cells and low concentrations of interleukin-2. This response could not be generated with thymocytes from naive animals. In each case the effect seen with the combination of a moderate CY dose (150 mg/kg) with TNF alpha was better than that seen with either dose of CY alone and equal to or better than that seen with the higher dose of CY combined with TNF alpha. These results indicate that treatment with a single moderate dose of CY in combination with TNF alpha is effective against a large, established tumor in this murine model. Furthermore, all the long-term survivors induced by this treatment developed protective immunity against reimplanted tumor and demonstrated a long-term specific immune memory in the thymus.

CpG oligodeoxynucleotide induces apoptosis and cell cycle arrest in A20 lymphoma cells via TLR9-mediated pathways.

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Qi, Xu-Feng; Zheng, Li; Kim, Cheol-Su; Lee, Kyu-Jae; Kim, Dong-Heui; Cai, Dong-Qing; Qin, Jun-Wen; Yu, Yan-Hong; Wu, Zheng; Kim, Soo-Ki

2013-07-01

Recent studies have suggested that the anti-cancer activity of CpG-oligodeoxynucleotides (CpG-ODNs) is owing to their immunomodulatory effects in tumor-bearing host. The purpose of this study is to investigate the directly cytotoxic activity of KSK-CpG, a novel CpG-ODN with an alternative CpG motif, against A20 and EL4 lymphoma cells in comparison with previously used murine CpG motif (1826-CpG). To evaluate the potential cytotoxic effects of KSK-CpG on lymphoma cells, cell viability assay, confocal microscopy, flow cytometry, DNA fragmentation, Western blotting, and reverse transcription-polymerase chain reaction (RT-PCR) analysis were used. We found that KSK-CpG induced direct cytotoxicity in A20 lymphoma cells, but not in EL4 lymphoma cells, at least in part via TLR9-mediated pathways. Apoptotic cell death was demonstrated to play an important role in CpG-ODNs-induced cytotoxicity. In addition, both mitochondrial membrane potential decrease and G1-phase arrest were involved in KSK-CpG-induced apoptosis in A20 cells. The activities of apoptotic molecules such as caspase-3, PARP, and Bax were increased, but the activation of p27 Kip1 and ERK were decreased in KSK-CpG-treated A20 cells. Furthermore, autocrine IFN-γ partially contributed to apoptotic cell death in KSK-CpG-treated A20 cells. Collectively, our findings suggest that KSK-CpG induces apoptotic cell death in A20 lymphoma cells at least in part by inducing G1-phase arrest and autocrine IFN-γ via increasing TLR9 expression, without the need for immune system of tumor-bearing host. This new understanding supports the development of TLR9-targeted therapy with CpG-ODN as a direct therapeutic agent for treating B lymphoma. Copyright © 2013 Elsevier Ltd. All rights reserved.

Therapeutic Outcome of Extranodal NK/T-Cell Lymphoma Initially Treated with Chemotherapy

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Kim, Byung Su; Kim, Tae-you; Kim, Chul Woo; Kim, Ji Yeun; Heo, Dae Seog; Bang, Yung-jue; Kim, Noe Kyeong [Seoul National Univ. College of Medicine (Korea, Republic of). Cancer Research Inst.

2003-11-01

The therapeutic outcome of chemotherapy in NK/T cell lymphoma (NTCL) has not been well documented until now. The aims of this study were to investigate the outcome of chemotherapy and to evaluate the clinical factors influencing the responsiveness to chemotherapy. Between 1995 and 2000, 59 patients received anthracycline-based chemotherapy as an initial treatment. Forty-five patients had nasal NTCL, whereas 14 had extranasal NTCL. Forty-one patients had stage I/II and 18 had stage III/IV disease. Epstein-Barr virus status was positive in 67.6% of cases. The results of initial chemotherapy were complete remission in 35.6% of the patients, 2-year disease-free survival in 22.9% and 2-year overall survival in 44.2%. Adjuvant radiotherapy after chemotherapy did not improve outcome in stage I/II nasal NTCL. The International Prognostic Index was a significant prognostic factor of complete remission rate, and stage was also significant for disease-free survival.

Therapeutic Outcome of Extranodal NK/T-Cell Lymphoma Initially Treated with Chemotherapy

International Nuclear Information System (INIS)

Kim, Byung Su; Kim, Tae-you; Kim, Chul Woo; Kim, Ji Yeun; Heo, Dae Seog; Bang, Yung-jue; Kim, Noe Kyeong

2003-01-01

The therapeutic outcome of chemotherapy in NK/T cell lymphoma (NTCL) has not been well documented until now. The aims of this study were to investigate the outcome of chemotherapy and to evaluate the clinical factors influencing the responsiveness to chemotherapy. Between 1995 and 2000, 59 patients received anthracycline-based chemotherapy as an initial treatment. Forty-five patients had nasal NTCL, whereas 14 had extranasal NTCL. Forty-one patients had stage I/II and 18 had stage III/IV disease. Epstein-Barr virus status was positive in 67.6% of cases. The results of initial chemotherapy were complete remission in 35.6% of the patients, 2-year disease-free survival in 22.9% and 2-year overall survival in 44.2%. Adjuvant radiotherapy after chemotherapy did not improve outcome in stage I/II nasal NTCL. The International Prognostic Index was a significant prognostic factor of complete remission rate, and stage was also significant for disease-free survival

Bone Tumor Environment as a Potential Therapeutic Target in Ewing Sarcoma.

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Redini, Françoise; Heymann, Dominique

2015-01-01

Ewing sarcoma is the second most common pediatric bone tumor, with three cases per million worldwide. In clinical terms, Ewing sarcoma is an aggressive, rapidly fatal malignancy that mainly develops not only in osseous sites (85%) but also in extra-skeletal soft tissue. It spreads naturally to the lungs, bones, and bone marrow with poor prognosis in the two latter cases. Bone lesions from primary or secondary (metastases) tumors are characterized by extensive bone remodeling, more often due to osteolysis. Osteoclast activation and subsequent bone resorption are responsible for the clinical features of bone tumors, including pain, vertebral collapse, and spinal cord compression. Based on the "vicious cycle" concept of tumor cells and bone resorbing cells, drugs, which target osteoclasts, may be promising agents as adjuvant setting for treating bone tumors, including Ewing sarcoma. There is also increasing evidence that cellular and molecular protagonists present in the bone microenvironment play a part in establishing a favorable "niche" for tumor initiation and progression. The purpose of this review is to discuss the potential therapeutic value of drugs targeting the bone tumor microenvironment in Ewing sarcoma. The first part of the review will focus on targeting the bone resorbing function of osteoclasts by means of bisphosphonates or drugs blocking the pro-resorbing cytokine receptor activator of NF-kappa B ligand. Second, the role of this peculiar hypoxic microenvironment will be discussed in the context of resistance to chemotherapy, escape from the immune system, or neo-angiogenesis. Therapeutic interventions based on these specificities could be then proposed in the context of Ewing sarcoma.

Primary intestinal T cell lymphomas in Indian patients - In search of enteropathic T cell lymphoma

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Shet Tanuja

2010-07-01

Full Text Available Objective: This series of six intestinal T cell lymphomas (ITCL attempts to document enteropathy-associated T cell lymphoma (EATCL in India. Materials and Methods: A total of six ITCL were selected from 170 gastrointestinal lymphomas in last 10 years. Results: The cases studied included EATCL (4, ITCL with a CD4 positive phenotype (1 and ITCL NK/T cell type (1. Of the four EATCL, two occurred in the ileum, one in right colon and one in duodenum. In three EATCL cases, there was history of celiac disease or lactose intolerance and enteropathic changes were noted in the adjacent mucosa. These tumors had CD3+/CD8+/CD56 (+/-/CD4-/ Granzyme B+ immunophenotype. One EATCL was monomorphic small cell type (type II EATCL with a CD3+/CD8-CD56+/CD4-/ Granzyme B+ phenotype. EBER- ISH (Epstein Barr virus coded RNA′s- in situ hybridization revealed positive tumor cells in ITCL NK/T cell type and in bystander cells in three EATCL. Conclusion: ITCL are rare in Indian patients but do occur and comprise a mixture of the enteropathic and non-enteropathic subtypes.

Imaging of supradiaphragmatic manifestations of extranodal nonHodgkin's lymphoma

International Nuclear Information System (INIS)

Cohnen, M.; Saleh, A.; Engelbrecht, V.; Moedder, U.; Germing, U.

2002-01-01

Malignant lymphomas are differentiated into Hodgkin's and non-Hodgkin's-lymphoma (NHL). The following article discusses the imaging of extranodal NHL in supradiaphragmatic localizations. Lymphoma can affect nearly all tissues, and represent a rare entity as primary extranodal NHL. A secondary involvement of non-nodal tissue as consequence of a generalized lymphoproliferative disease is more common,and may be seen as well in HIV-positive patients defining AIDS. As extranodal lymphoma mimick the radiologic appearance of other malignant tumors, direct diagnosis without histologic analysis is often impossible. The article describes typical manifestations of lymphoma of the lungs, the head and neck area including the large glands, and rare localizations as the heart or the breast. (orig.) [de

Primary intracranial malignant lymphoma. Report of nine cases

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Matsumoto, Mikiro; Ohtsuka, Takatsugu; Kuroki, Takao; Shibata, Iekado; Terao, Hideo; Kudo, Motoshige

1988-12-01

Nine cases of primary intracranial malignant lymphoma, which accounts for 3.3 % of all intracranial tumors seen in the authors' institution, were studied in terms of diagnostic computed tomographic (CT) features, the tumors' histologic appearance, treatment, post-treatment blood immunologic and cerebrospinal fluid (CSF) characteristics, and outcome. The patients were seven males and two females aged 42 to 67 years. Their chief signs and symptoms on admission were intracranial hypertension, focal signs, and disturbance of consciousness. CT, which proved the most useful preoperative diagnostic technique, demonstrated multiple lesions in seven cases and, in all cases, regions of isodensity or slight high density that were enhanced by contrast medium. According to the patterns of enhancement, the tumors were classed as diffuse (three cases) or nodular (six cases). The former is considered typical of malignant lymphoma, whereas the latter type was sometimes indistinguishable from metastatic tumor and meningioma. At surgery, one patient underwent radical tumor excision, two partial removal, and six biopsy only. Histologic examination revealed one tumor to be of the diffuse small cell type, three of the medium cell type, and five of the large cell type (Lymphoma Study Group classification). Of seven tumors in which lymphocytes were examined by peroxidase-antiperoxidase staining, four were of the B cell type. Postoperatively, whole brain irradiation with 29 to 46 Gy was followed by local irradiation with 15 to 50 Gy. If the tumor persisted, one of three chemotherapies was administered. In one case, methotrexate was given intrathecally. Seven patients were divided into two groups: long remission (three) and recurrence (four). These two groups were compared in terms of serum immunoglobulin levels, T and B cell ratios, CSF characteristics, CT features, tumor cell type, and treatment. No clear differences were found.

[Primary peripheral T-cell lymphoma of the penis: a case report and review of the literature].

Science.gov (United States)

Shi, Yan-Lin; Yin, Hong-Lin; Zhou, Xiao-Jun; Zhou, Hang-Bo; Lu, Zhen-Feng

2008-11-01

To report a case of primary peripheral T-cell lymphoma of the penis. We analyzed the clinicopathological characteristics of the case of primary peripheral T-cell lymphoma using histological, cytochemical and immunohistochemical methods and by review of the literature. The patient was a 65 years old man and presented with a diffuse enlargement of the penis as the initial sign, followed by erosive ulcer in the caput penis and inguinal lymphadenectasis. The tumor was pathohistologically manifested as an epidermal ulcer, with tumorous necrosis around the capillary, infiltrative growth and atypical changes of the neoplastic cells and proliferation of capillaries. Immunohistochemically, the tumor cells were positive for CD43 and CD3, but negative for CD20, CD79a, CD34, CD30, CD56 and CD34. Clinically it responded to the chemotherapy designed for peripheral T-cell lymphoma. Primary peripheral T-cell lymphoma of the penis is an extremely rare malignant tumor, the diagnosis of which relies on histopathological examination, immunohistochemical staining and differentiation between squamous cell carcinoma and other types of lymphoma.

A case of lymphoma presented with acute renal failure

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Mustafa Yaprak

2017-03-01

Full Text Available Acute renal failure (ARF in patients with malignancy occurs due to causes such as prerenal, renal and post renal as in normal population. Tumor infiltration of kidneys is usually uncommon. However, renal function may be impaired in fast-growing hematological malignancies such as acute leukemia or lymphoma, depending on tumor involvement. Herein, we presented a case of ARF and later diagnosed as B-cell Non-Hodgkin's lymphoma. 54-year-old male patient was admitted due to ARF. Although development of ARF due to tumor infiltration is rare, in cases who did not have risk factors for development of ARF, leukemic or lymphomatous infiltration should be considered. [Cukurova Med J 2017; 42(1.000: 168-171

ENO1 promotes tumor proliferation and cell adhesion mediated drug resistance (CAM-DR) in Non-Hodgkin's Lymphomas

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Zhu, Xinghua; Miao, Xiaobing; Wu, Yaxun; Li, Chunsun; Guo, Yan; Liu, Yushan; Chen, Yali; Lu, Xiaoyun [Department of Pathology, Affiliated Cancer Hospital of Nantong University, 30 North Tongyang Road, Pingchao, Nantong 226361, Jiangsu (China); Wang, Yuchan, E-mail: wangyuchannt@126.com [Department of Pathogen and Immunology, Medical College, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu (China); He, Song, E-mail: hesongnt@126.com [Department of Pathology, Affiliated Cancer Hospital of Nantong University, 30 North Tongyang Road, Pingchao, Nantong 226361, Jiangsu (China)

2015-07-15

Enolases are glycolytic enzymes responsible for the ATP-generated conversion of 2-phosphoglycerate to phosphoenolpyruvate. In addition to the glycolytic function, Enolase 1 (ENO1) has been reported up-regulation in several tumor tissues. In this study, we investigated the expression and biologic function of ENO1 in Non-Hodgkin's Lymphomas (NHLs). Clinically, by western blot analysis we observed that ENO1 expression was apparently higher in diffuse large B-cell lymphoma than in the reactive lymphoid tissues. Subsequently, immunohistochemical staining of 144 NHLs suggested that the expression of ENO1 was significantly lower in the indolent lymphomas compared with the progressive lymphomas. Further, we identified ENO1 as an independent prognostic factor, and it was significantly correlated with overall survival of NHL patients. In addition, we found that ENO1 could promote cell proliferation, regulate cell cycle associated gene and PI3K/AKT signaling pathway in NHLs. Finally, we verified that ENO1 participated in the process of lymphoma cell adhesion mediated drug resistance (CAM-DR). Adhesion to FN or HS5 cells significantly protected OCI-Ly8 and Daudi cells from cytotoxicity compared with those cultured in suspension, and these effects were attenuated when transfected with ENO1-siRNA. Based on the study, we propose that inhibition of ENO1 expression may be a novel strategy for therapy for NHLs patients, and it may be a target for drug resistance. - Highlights: • ENO1 expression is reversely correlated with clinical outcomes of patients with NHLs. • ENO1 promotes the proliferation of NHL cells. • ENO1 regulates cell adhesion mediated drug resistance.

Therapeutically targeting cyclin D1 in primary tumors arising from loss of Ini1

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Smith, Melissa E.; Cimica, Velasco; Chinni, Srinivasa; Jana, Suman; Koba, Wade; Yang, Zhixia; Fine, Eugene; Zagzag, David; Montagna, Cristina; Kalpana, Ganjam V.

2011-01-01

Rhabdoid tumors (RTs) are rare, highly aggressive pediatric malignancies with poor prognosis and with no standard or effective treatment strategies. RTs are characterized by biallelic inactivation of the INI1 tumor suppressor gene. INI1 directly represses CCND1 and activates cyclin-dependent kinase (cdk) inhibitors p16Ink4a and p21CIP. RTs are exquisitely dependent on cyclin D1 for genesis and survival. To facilitate translation of unique therapeutic strategies, we have used genetically engineered, Ini1+/− mice for therapeutic testing. We found that PET can be used to noninvasively and accurately detect primary tumors in Ini1+/− mice. In a PET-guided longitudinal study, we found that treating Ini1+/− mice bearing primary tumors with the pan-cdk inhibitor flavopiridol resulted in complete and stable regression of some tumors. Other tumors showed resistance to flavopiridol, and one of the resistant tumors overexpressed cyclin D1, more than flavopiridol-sensitive cells. The concentration of flavopiridol used was not sufficient to down-modulate the high level of cyclin D1 and failed to induce cell death in the resistant cells. Furthermore, FISH and PCR analyses indicated that there is aneuploidy and increased CCND1 copy number in resistant cells. These studies indicate that resistance to flavopiridol may be correlated to elevated cyclin D1 levels. Our studies also indicate that Ini1+/− mice are valuable tools for testing unique therapeutic strategies and for understanding mechanisms of drug resistance in tumors that arise owing to loss of Ini1, which is essential for developing effective treatment strategies against these aggressive tumors. PMID:21173237

Radiation therapy for primary orbital lymphoma

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Chao, Cliff K.S.; Lin Hsiusan; Rao Devineni, V.; Smith, Morton

1995-01-01

Purpose: The influence of tumor size, grade, thoroughness of staging workup, and radiation dose on disease control, radiation-related complications, and incidence of systemic progression of primary orbital lymphoma is analyzed. Methods and Materials: Twenty patients with Stage I primary orbital lymphoma were treated from August 1976 through August 1991 at Mallinckrodt Institute of Radiology. Staging workups included physical examination, chest x-ray, complete blood count (CBC), liver function test, and computerized tomography (CT) scan of the orbit, abdomen, and pelvis. Nineteen patients had bone marrow biopsy. The histological types based on the National Cancer Institute working formulation were 9 low-grade and 11 intermediate-grade, including five lymphocytic lymphomas of intermediate differentiation. The extension of disease and the volume of tumor were evaluated by CT scan of the orbit. The most commonly used radiation therapy technique was single anterior direct field with 4 MV or 6 MV photons. Lens was shielded or not treated in eight patients. Dose ranged from 20 to 43.2 Gy. Thirteen of 20 patients received 30 Gy. Minimum follow-up was 24 months (median, 4 years). Results: Local control was achieved in all 20 patients. One patient with lymphocytic lymphoma with intermediate differentiation developed disseminated disease. Actuarial disease-free survival (DFS) was 100% and 90% at 2 and 5 years, respectively. No retinopathy was observed. Cataracts were noted in seven patients at 1 to 10 years following irradiation (median, 2 years). Three patients developed lacrimal function disorder, however, no corneal ulceration occurred. Conclusions: Thirty Gy in 15 fractions appears to be a sufficient dose for local control with acceptable morbidity, especially for low-grade, as well as certain types of intermediate-grade lymphomas, such as diffuse small cleaved cell and lymphocytic lymphoma of intermediate differentiation. Systemic dissemination is minimal, provided local

Radiation therapy for primary orbital lymphoma

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Chao, Cliff K.S.; Hsiusan, Lin; Rao Devineni, V; Smith, Morton

1995-02-15

Purpose: The influence of tumor size, grade, thoroughness of staging workup, and radiation dose on disease control, radiation-related complications, and incidence of systemic progression of primary orbital lymphoma is analyzed. Methods and Materials: Twenty patients with Stage I primary orbital lymphoma were treated from August 1976 through August 1991 at Mallinckrodt Institute of Radiology. Staging workups included physical examination, chest x-ray, complete blood count (CBC), liver function test, and computerized tomography (CT) scan of the orbit, abdomen, and pelvis. Nineteen patients had bone marrow biopsy. The histological types based on the National Cancer Institute working formulation were 9 low-grade and 11 intermediate-grade, including five lymphocytic lymphomas of intermediate differentiation. The extension of disease and the volume of tumor were evaluated by CT scan of the orbit. The most commonly used radiation therapy technique was single anterior direct field with 4 MV or 6 MV photons. Lens was shielded or not treated in eight patients. Dose ranged from 20 to 43.2 Gy. Thirteen of 20 patients received 30 Gy. Minimum follow-up was 24 months (median, 4 years). Results: Local control was achieved in all 20 patients. One patient with lymphocytic lymphoma with intermediate differentiation developed disseminated disease. Actuarial disease-free survival (DFS) was 100% and 90% at 2 and 5 years, respectively. No retinopathy was observed. Cataracts were noted in seven patients at 1 to 10 years following irradiation (median, 2 years). Three patients developed lacrimal function disorder, however, no corneal ulceration occurred. Conclusions: Thirty Gy in 15 fractions appears to be a sufficient dose for local control with acceptable morbidity, especially for low-grade, as well as certain types of intermediate-grade lymphomas, such as diffuse small cleaved cell and lymphocytic lymphoma of intermediate differentiation. Systemic dissemination is minimal, provided local

Primary central nervous system lymphoma in immunocompetent patients: spectrum of findings and differential characteristics.

Science.gov (United States)

Gómez Roselló, E; Quiles Granado, A M; Laguillo Sala, G; Pedraza Gutiérrez, S

2018-02-23

Primary central nervous system (CNS) lymphomas are uncommon and their management differs significantly from that of other malignant tumors involving the CNS. This article explains how the imaging findings often suggest the diagnosis early. The typical findings in immunocompetent patients consist of a supratentorial intraaxial mass that enhances homogeneously. Other findings to evaluate include multifocality and incomplete ring enhancement. The differential diagnosis of primary CNS lymphomas should consider mainly other malignant tumors of the CNS such as glioblastomas or metastases. Primary CNS lymphomas tend to have less edema and less mass effect; they also tend to spare the adjacent cortex. Necrosis, hemorrhage, and calcification are uncommon in primary CNS lymphomas. Although the findings in morphologic sequences are characteristic, they are not completely specific and atypical types are sometimes encountered. Advanced imaging techniques such as diffusion or especially perfusion provide qualitative and quantitative data that play an important role in differentiating primary CNS lymphomas from other brain tumors. Copyright © 2018 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Integrin α5β1, the Fibronectin Receptor, as a Pertinent Therapeutic Target in Solid Tumors

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Schaffner, Florence; Ray, Anne Marie; Dontenwill, Monique, E-mail: monique.dontenwill@unistra.fr [UMR 7213 CNRS, Laboratoire de Biophotonique et Pharmacologie, Tumoral signaling and therapeutic targets, Université de Strasbourg, Faculté de Pharmacie, 67401 Illkirch (France)

2013-01-15

Integrins are transmembrane heterodimeric proteins sensing the cell microenvironment and modulating numerous signalling pathways. Changes in integrin expression between normal and tumoral cells support involvement of specific integrins in tumor progression and aggressiveness. This review highlights the current knowledge about α5β1 integrin, also called the fibronectin receptor, in solid tumors. We summarize data showing that α5β1 integrin is a pertinent therapeutic target expressed by tumoral neovessels and tumoral cells. Although mainly evaluated in preclinical models, α5β1 integrin merits interest in particular in colon, breast, ovarian, lung and brain tumors where its overexpression is associated with a poor prognosis for patients. Specific α5β1 integrin antagonists will be listed that may represent new potential therapeutic agents to fight defined subpopulations of particularly aggressive tumors.

Follicular lymphoma in the palate with clinical appearance similar to salivary gland tumors.

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Lima, Marina de Deus Moura; Artico, Gabriela; Soares, Fernando Augusto; Martins, Marília Trierveiler; Alves, Fabio Abreu

2010-09-01

Intraoral presentation of follicular lymphoma is rare, and only three cases in the palate have been reported to date. The present case report describes an uncommon case of follicular lymphoma affecting the palate. The clinical aspect was similar to salivary gland neoplasm, and an incisional biopsy was important to establish the correct diagnosis and consequently to plan the treatment. Also discussed is the differential diagnosis among follicular lymphoma, mucosa-associated lymphoid tissue lymphoma, and follicular lymphoid hyperplasia with regard to the histopathologic and immunohistochemical features.

A case of cutaneous large B-cell lymphoma of the legs appearing as chronic venous ulceration

Directory of Open Access Journals (Sweden)

Marta Carlesimo

2012-04-01

Full Text Available We report here a case of a woman with a cutaneous large B-cell lymphoma of the legs. She had a plaque lesion, superficially ulcerated and necrotized with tumorous borders situated on the posterior side of the right leg and two red or bluish-red nodular lesions. A skin biopsy from both nodular and plaque lesion showed a diffuse infiltrate of atypical large B cells CD20+ and CD79a+, spanning epidermis, dermis and subcutaneous tissue. A therapeutic approach containing anti-CD20 monoclonal antibody (rituximab was suggested.

Evans Syndrome Presented with Marginal Zone Lymphoma and Duodenal Neuroendocrine Tumor in an Elderly Woman

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Daniele D'Ambrosio

2016-12-01

Full Text Available Evans syndrome (ES is an autoimmune disorder characterized by simultaneous or sequential development of autoimmune hemolytic anemia, immune thrombocytopenia, and/or neutropenia. ES can be classified as a primary (idiopathic or secondary (associated with an underlying disease syndrome. We report a case of ES in an elderly patient in the presence of multiple trigger factors such as recent influenza vaccine, marginal zone lymphoma, and neuroendocrine tumor G1. Whether this association is casual or causal remains a matter of speculation. It is however necessary to have a thorough work-up in a newly diagnosed ES and a more accurate search of miscellaneous factors especially in elderly patients.

CCR investigators use liquid biopsies to uncover cancer in the blood of lymphoma patients | Center for Cancer Research

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CCR investigators are using circulating tumor DNA (ctDNA) as a type of noninvasive liquid biopsy for patients with diffuse large B-cell lymphoma (DLBCL), the most common type of non-Hodgkin lymphoma. are using circulating tumor DNA (ctDNA) as a type of noninvasive liquid biopsy for patients with diffuse large B-cell lymphoma (DLBCL), the most common type of non-Hodgkin

Increased Plasma Colloid Osmotic Pressure Facilitates the Uptake of Therapeutic Macromolecules in a Xenograft Tumor Model

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Matthias Hofmann

2009-08-01

Full Text Available Elevated tumor interstitial fluid pressure (TIFP is a characteristic of most solid tumors. Clinically, TIFP may hamper the uptake of chemotherapeutic drugs into the tumor tissue reducing their therapeutic efficacy. In this study, a means of modulating TIFP to increase the flux of macromolecules into tumor tissue is presented, which is based on the rationale that elevated plasma colloid osmotic pressure (COP pulls water from tumor interstitium lowering the TIFP. Concentrated human serum albumin: (20% HSA, used as an agent to enhance COP, reduced the TIFP time-dependently from 8 to 2 mm Hg in human tumor xenograft models bearing A431 epidermoid vulva carcinomas. To evaluate whether this reduction facilitates the uptake of macromolecules, the intratumoral distribution of fluorescently conjugated dextrans (2.5 mg/ml and cetuximab (2.0 mg/ml was probed using novel time domain nearinfrared fluorescence imaging. This method permitted discrimination and semiquantification of tumor-accumulated conjugate from background and unspecific probe fluorescence. The coadministration of 20% HSA together with either dextrans or cetuximab was found to lower the TIFP significantly and increase the concentration of the substances within the tumor tissue in comparison to control tumors. Furthermore, combined administration of 20%HSA plus cetuximab reduced the tumor growth significantly in comparison to standard cetuximab treatment. These data demonstrate that increased COP lowers the TIFP within hours and increases the uptake of therapeutic macromolecules into the tumor interstitium leading to reduced tumor growth. This model represents a novel approach to facilitate the delivery of therapeutics into tumor tissue, particularly monoclonal antibodies.

Marker-controlled watershed for lymphoma segmentation in sequential CT images

International Nuclear Information System (INIS)

Yan Jiayong; Zhao Binsheng; Wang, Liang; Zelenetz, Andrew; Schwartz, Lawrence H.

2006-01-01

Segmentation of lymphoma containing lymph nodes is a difficult task because of multiple variables associated with the tumor's location, intensity distribution, and contrast to its surrounding tissues. In this paper, we present a reliable and practical marker-controlled watershed algorithm for semi-automated segmentation of lymphoma in sequential CT images. Robust determination of internal and external markers is the key to successful use of the marker-controlled watershed transform in the segmentation of lymphoma and is the focus of this work. The external marker in our algorithm is the circle enclosing the lymphoma in a single slice. The internal marker, however, is determined automatically by combining techniques including Canny edge detection, thresholding, morphological operation, and distance map estimation. To obtain tumor volume, the segmented lymphoma in the current slice needs to be propagated to the adjacent slice to help determine the external and internal markers for delineation of the lymphoma in that slice. The algorithm was applied to 29 lymphomas (size range, 9-53 mm in diameter; mean, 23 mm) in nine patients. A blinded radiologist manually delineated all lymphomas on all slices. The manual result served as the ''gold standard'' for comparison. Several quantitative methods were applied to objectively evaluate the performance of the segmentation algorithm. The algorithm received a mean overlap, overestimation, and underestimation ratios of 83.2%, 13.5%, and 5.5%, respectively. The mean average boundary distance and Hausdorff boundary distance were 0.7 and 3.7 mm. Preliminary results have shown the potential of this computer algorithm to allow reliable segmentation and quantification of lymphomas on sequential CT images

Primary conjunctival follicular lymphoma mimicking chronic conjunctivitis.

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Labrador Velandia, S; García Lagarto, E; Saornil, M A; García Álvarez, C; Cuello, R; Diezhandino, P

2016-02-01

The case is presented of a 43 year-old male patient with chronic follicular conjunctivitis, negative bacterial serology, and refractory to local treatment. The incisional biopsy performed showed to be consistent with reactive lymphoid hyperplasia. A year later, a new incisional biopsy showed follicular lymphoma, with no systemic involvement, and he was treated with local radiotherapy. When a chronic follicular conjunctivitis is refractory to treatment, it is essential to perform an incisional biopsy to establish the histopathological diagnosis that can range from chronic inflammation, reactive lymphoid hyperplasia to lymphoma. Follicular lymphoma is rare among conjunctival lymphomas, and the staging is indispensable for the correct therapeutic approach. Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

Analysis of the expression level and methylation of tumor protein p53, phosphatase and tensin homolog and mutS homolog 2 in N-methyl-N-nitrosourea-induced thymic lymphoma in C57BL/6 mice.

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Huo, Xueyun; Li, Zhenkun; Zhang, Shuangyue; Li, Changlong; Guo, Meng; Lu, Jing; Lv, Jianyi; Du, Xiaoyan; Chen, Zhenwen

2017-10-01

Tumorigenesis is often caused by somatic mutation or epigenetic changes in genes that regulate aspects of cell death, proliferation and survival. Although the functions of multiple tumor suppressor genes have been well studied in isolation, how these genes cooperate during the progression of a single tumor remains unclear in numerous cases. The present study used N-methyl-N-nitrosourea (MNU), one of the most potent mutagenic nitrosourea compounds, to induce thymic lymphoma in C57BL/6J mice. Subsequently, the protein expression levels of phosphatase and tensin homolog (PTEN), transformation protein 53 and mutS homolog 2 (MSH2) were evaluated concomitantly in the thymus, liver, kidney and spleen of MNU-treated mice by western blotting. To determine whether changes in expression level were due to aberrant epigenetic regulation, the present study further examined the methylation status of each gene by MassARRAY analysis. During the tumorigenesis process of an MNU-induced single thymic lymphoma, the expression level of PTEN was revealed to be reduced in thymic lymphoma samples but not in normal or non-tumor thymus tissue samples. Furthermore, a marked reduction of P53 expression levels were demonstrated in thymic lymphomas and spleens with a metastatic tumor. Conversely, MSH2 upregulation was identified only in liver, kidney, and spleen samples that were infiltrated by thymic lymphoma cells. Furthermore, the present study revealed that a number of 5'-C-phosphate-G-3' sites located in the promoter of aberrantly expressed genes had significantly altered methylation statuses. These results improve the understanding of the course of mutagen-induced cancer, and highlight that epigenetic regulation may serve an important function in cancer.

Angiogenesis in non-Hodgkin's lymphoma: clinico-pathological correlations and prognostic significance in specific subtypes

DEFF Research Database (Denmark)

Jørgensen, Judit Meszaros; Sørensen, Flemming Brandt; Bendix, K

2007-01-01

The aim of the study was to evaluate angiogenesis in different subtypes of non-Hodgkin's lymphoma (NHL) and to correlate angiogenic scores to clinical endpoints. Pre-therapeutic lymph node biopsies from 308 patients with NHL [107 follicular B-cell lymphoma (FL), 94 diffuse large B-cell lymphoma (...

Angiogenesis in non-Hodgkin's lymphoma: clinico-pathological correlations and prognostic significance in specific subtypes

DEFF Research Database (Denmark)

Jørgensen, J M; Sørensen, Flemming Brandt; Bendix, K

2007-01-01

The aim of the study was to evaluate angiogenesis in different subtypes of non-Hodgkin's lymphoma (NHL) and to correlate angiogenic scores to clinical endpoints. Pre-therapeutic lymph node biopsies from 308 patients with NHL [107 follicular B-cell lymphoma (FL), 94 diffuse large B-cell lymphoma...

Endogenous pyrogen production by Hodgkin's disease and human histiocytic lymphoma cell lines in vitro.

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Bodel, P; Ralph, P; Wenc, K; Long, J C

1980-02-01

Fever not explained by infection may occur in patients with malignant lymphoma presumably caused by a release of endogenous pyrogen. Although pyrogen has been found in some tumors with a mixed cell population, production of endogenous pyrogen by the neoplastic cells has not been demonstrated. This report documents the apparently spontaneous synthesis and release of such pyrogen by two human tumor cell lines derived from patients with Hodgkin's disease and histiocytic lymphoma. The endogenous pyrogen from the two cell lines was similar and closely resembled that produced by normal human monocytes in antigenic properties as well as heat and pronase sensitivity. The Hodgkin's disease and histiocytic lymphoma cell lines do not require specific stimulation for the production of endogenous pyrogen suggesting that the mechanism of pyrogen release by neoplastic macrophage-related cells differs from that of normal phagocytic cells. The tumor-associated fever in some patients with malignant lymphoma may be caused by a release of endogenous pyrogen by proliferating neoplastic cells.

Primary Diffuse Large Cell Lymphoma of the Bladder: Case Report and Literature Review

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Mansour Ansari

2017-01-01

Full Text Available Most bladder tumors are epithelial in origin. Nonepithelial cancers are rarely located in the bladder. Sarcomas are the most common malignancies among nonepithelial cancers. Primary bladder lymphoma is rare and mostly low grade. Here, we have reported a case of diffuse large cell lymphoma of the bladder. The patient, a 64-year-old man, had urinary frequency for 18 months. Abdominal sonography indicated a thick bladder wall and transurethral biopsy showed diffuse large cell lymphoma. Immunohistochemistry (IHC results showed that the tumor was positive for CD20, CD45, and Pax-5 and negative for BCL-2, cytokeratin, and S100. He had a normal bone marrow biopsy, abdominal, pelvic and chest CT scans. He had no B symptoms. The patient received 6 cycles of R-CHOP followed by radiotherapy (36 Gy to the pelvis. Six months after treatment, the patient is well and has returned to work. We have searched PubMed for primary diffuse large cell lymphoma. Primary diffuse large cell lymphoma of the bladder is best treated according to treatment for diffuse large cell lymphoma of other sites, which includes chemotherapy and radiotherapy. As seen in our review, primary diffuse large cell lymphoma of the bladder has a similar clinical course to diffuse large cell lymphoma of other sites.

Clinical relevance of consolidation radiotherapy and other main therapeutic issues in primary central nervous system lymphomas treated with upfront high-dose methotrexate

International Nuclear Information System (INIS)

Reni, Michele; Ferreri, Andres J.M.; Guha-Thakurta, Nandita; Blay, Jean-Yves; Dell'Oro, Stefania; Biron, Pierre; Hochberg, Fred H.

2001-01-01

Purpose: To evaluate the optimal dose of methotrexate (MTX) and the efficacy of other drugs, intrathecal chemotherapy (CHT), and radiotherapy (RT) in primary brain lymphomas. Methods and Materials: Two hundred eighty-eight immunocompetent patients with histologically documented, previously untreated primary brain lymphomas, receiving CHT containing high-dose MTX (≥1 g/m 2 ) with or without RT were selected from 19 prospective series. The impact on survival of the MTX dose ( 2 vs.≥3 g/m 2 ), the main drugs, intrathecal CHT, and combination CHT (mono-CHT vs. poly-CHT) was assessed, according to the intention-to-treat principle. The role of post-CHT irradiation (immediate vs. delayed RT) was evaluated in 119 patients with a complete response to CHT. The whole brain and tumor bed dose ( 2 (p=0.04), thiotepa (p=0.03), and intrathecal CHT (p=0.03) improved the OS, and nitrosoureas (p 0.01) correlated with a worse survival. In multivariate analysis, limited to patients receiving MTX ≥3 g/m 2 , only the addition of cytarabine improved the OS; nitrosoureas reduced MTX efficacy. Of the 119 complete responders, 70 received immediate RT. A RT dose of ≥40 Gy to the whole brain or tumor bed did not improve OS. The 3-year OS was similar between the immediate and delayed RT groups. In multivariate analysis, RT delay had no negative impact on survival. Conclusions: MTX ≥3 g/m 2 seems to improve survival in primary brain lymphoma patients. The efficacy of additional drugs, except for cytarabine, remains unproved. Randomized trials are needed to confirm that RT withdrawal yields no detrimental effect in complete responders

Discrimination of different brain metastases and primary CNS lymphomas using morphologic criteria and diffusion tensor imaging

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Bette, S.; Wiestler, B.; Huber, T.; Boeckh-Behrens, T.; Zimmer, C.; Kirschke, J. [Technical University Munich, Klinikum rechts der Isar (Germany). Dept. of Neuroradiology; Delbridge, C. [Technical University Munich, Klinikum rechts der Isar (Germany). Dept. of Neuropathology; Meyer, B.; Gempt, J. [Technical University Munich, Klinikum rechts der Isar (Germany). Dept. of Neurosurgery

2016-12-15

Brain metastases are a common complication of cancer and occur in about 15-40% of patients with malignancies. The aim of this retrospective study was to differentiate between metastases from different primary tumors/CNS lymphyomas using morphologic criteria, fractional anisotropy (FA) and apparent diffusion coefficient (ADC). Morphologic criteria such as hemorrhage, cysts, pattern of contrast enhancement and location were reported in 200 consecutive patients with brain metastases/primary CNS lymphomas. FA and ADC values were measured in regions of interest (ROIs) placed in the contrast-enhancing tumor part, the necrosis and the non-enhancing peritumoral region (NEPTR). Differences between histopathological subtypes of metastases were analyzed using non-parametric tests, decision trees and hierarchical clustering analysis. Significant differences were found in morphologic criteria such as hemorrhage or pattern of contrast enhancement. In diffusion measurements, significant differences between the different tumor entities were only found in ADC analyzed in the contrast-enhancing tumor part. Among single tumor entities, primary CNS lymphomas showed significantly lower median ADC values in the contrast-enhancing tumor part (ADC{sub lymphoma} 0.92 [0.83-1.07] vs. ADC{sub no} {sub lymphoma} 1.35 [1.10-1.64] P=0.001). Further differentiation between types of metastases was not possible using FA and ADC. There were morphologic differences among the main subtypes of brain metastases/CNS lymphomas. However, due to a high variability of common types of metastases and low specificity, prospective differentiation remained challenging. DTI including FA and ADC was not a reliable tool for differentiation between different histopathological subtypes of brain metastases except for CNS lymphomas showing lower ADC values. Biopsy, surgery and staging remain essential for diagnosis.

The mantle cells lymphoma: a proposed treatment

International Nuclear Information System (INIS)

Chavez Martinez, Marlene Elizabeth

2012-01-01

A literature review was performed on mantle cells lymphoma in the therapeutic schemes. The literature that has been used is published in journals of medicine specializing in hematology, oncology, radiation therapy, molecular biology and internal medicine. The literature review was performed to propose a scheme of treatment according to Costa Rica. Epigenetic alterations have been revealed in patients with mantle lymphoma on current researches. The mantle lymphoma pathology has been described in various forms of clinical and histological presentation, stressing the importance of detailing the different methods and diagnostic reports. Working groups have proposed and developed various chemotherapy regimens and concluded that CHOP alone is without effect in mantle cell lymphoma unlike R-hyper-CVAD, CHOP / DHAP, high-dose Ara-C. Researchers have tried to develop new treatments based vaccines, use of modified viruses, specific monoclonal antibodies. The classic treatment has been triple intrathecal therapy. The central nervous system has been one of the most momentous sites of mantle cell lymphoma infiltration because poorer patient prognosis [es

L-type amino-acid transporter 1 (LAT1): a therapeutic target supporting growth and survival of T-cell lymphoblastic lymphoma/T-cell acute lymphoblastic leukemia

NARCIS (Netherlands)

Rosilio, C.; Nebout, M.; Imbert, V.; Griessinger, E.; Neffati, Z.; Benadiba, J.; Hagenbeek, T.; Spits, H.; Reverso, J.; Ambrosetti, D.; Michiels, J.-F.; Bailly-Maitre, B.; Endou, H.; Wempe, M. F.; Peyron, J.-F.

2015-01-01

The altered metabolism of cancer cells is a treasure trove to discover new antitumoral strategies. The gene (SLC7A5) encoding system L amino-acid transporter 1 (LAT1) is overexpressed in murine lymphoma cells generated via T-cell deletion of the pten tumor suppressor, and also in human T-cell acute

Transplantability of human lymphoid cell line, lymphoma, and leukemia in splenectomized and/or irradiated nude mice

International Nuclear Information System (INIS)

Watanabe, S.; Shimosato, Y.; Kuroki, M.; Sato, Y.; Nakajima, T.

1980-01-01

The effects of splenectomy and/or whole-body irradiation of nude mice before xenotransplantation of lymphoid cell lines, lymphoma, and leukemia were studied. Transplantation after whole-body irradiation resulted in the increased ''take'' rate of three cultured cell lines (two of T-cell-derived acute lymphocytic leukemia and one of B-cell derived acute lymphocytic leukemia) and in the tumorous growth of Burkitt-derived Raji and spontaneously transformed lymphoblastoid cell lines. With splenectomy plus irradiation as a pretreatment, tumorous growth occurred in four other cell lines which were not transplantable after irradiation only (two cell lines of Epstein-Barr virus-transformed cord blood cells and one each of null acute lymphocytic leukemia and nodular lymphoma-derived cell lines). Direct transplantation of leukemia and lymphoma cells into the pretreated mice was successful in 7 of 24 cases (29%). B-cell-derived diffuse large lymphoid lymphoma was transplantable in three of seven cases (43%). However, lymphoma and leukemia of peripheral T-cell origin was difficult to transplant even with pretreatment, and only one pleomorphic T-cell lymphoma grew to a significant size (2 cm). One tumor each of B-cell-derived diffuse large lymphoid and T-cell diffuse lymphoblastic lymphoma became transplantable

Radiotherapy of adult nodal non Hodgkin's lymphoma

International Nuclear Information System (INIS)

Gamen, G.; Thirion, P.

1999-01-01

The role of radiotherapy in the treatment of nodal non-Hodgkin's lymphoma has been modified by the introduction of efficient chemotherapy and the development of different pathological classifications. The recommended treatment of early-stage aggressive lymphomas is primarily a combination chemotherapy. The interest of adjuvant radiotherapy remains unclear and has to be established through large prospective trials. If radiation therapy has to be delivered, the historical results of exclusive radiation therapy showed that involved-fields and a dose of 35-40 Gy (daily fraction of 1.8 Gy, 5 days a week) are the optimal schedule. The interest of radiotherapy in the treatment of advanced-stage aggressive lymphoma is yet to be proven. Further studies had to stratify localized stages according to the factors of the International Prognostic Index. For easy-stage low-grade lymphoma, radiotherapy remains the standard treatment. However, the appropriate technique to use is controversial. Involved-field irradiation at a dose of 35 Gy seems to be the optimal schedule, providing a 10 year disease-free survival rate of 50 % and no major toxicity. There is no standard indication of radiotherapy in the treatment advanced-stage low-grade lymphoma. For 'new' nodal lymphoma's types, the indication of radiotherapy cannot be established (mantle-zone lymphoma, marginal zone B-cell lymphoma) or must take into account the natural history (Burkitt's lymphoma, peripheral T-cell lymphoma) and the sensibility to others therapeutic methods. (authors)

MALT LYMPHOMA OF PALATE AND ORBIT

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VIVIANA ANDREA CIFUENTES NAVAS

2018-05-01

Full Text Available TITLE: Malt palate and orbit lymphoma  Authors: CIFUENTES NAVAS-Viviana Andrea; MARTÍN PASCUAL- María Consolación; FERNÁNDEZ RODRÍGUEZ- Ana; ALONSO MESONERO- Marta; CHAVIANO GRAHJERA-Juan; MORAIS PÉREZ-Darío. INTRODUCTIONMALT-type lymphomas are lymphoid proliferations originated in the glandular epithelium of organs like the stomach, the salivary and lacrimal glands, and even, we can find lymphoid neoformations of non-epithelial localization, like in the orbital soft tissue. The lymphomas of the mucosal-associated lymphatic tissue (MALT represent only 0.2-0.3% and constitute a well-defined group of non-Hodgkin lymphomas of B origin. In the field of oral pathology, the salivary glands, tonsils and palate are mainly affected, it is more rare to find it in jugal mucosa.We present a rare case of MALT lymphoma with involvement of the palate and orbit. MATERIAL AND METHODS84-year-old patient with multiple pathologies. Derived from his primary care physician due to pharyngeal complaints of 4 to 5 days of evolution, associated with a painful palate lesion.He presented in right hemipaladar a tumoration of elastic consistency in submucosa, ulcerated in the center, with normal neck. Also left orbital tumor that limits the visual field. RESULTSCT and MRI of the neck report mass of 4x4 x2.5 cm in right hemipaladar, noninfiltrating concordant with possible lymphoma. The orbital MRI describes an intra and extra nasal left nasal lesion of 2.3x1.2x2 cm with characteristics consistent with lymphoma. CT of the neck: It demostrates a great mass of right hemipaladar, with lobulated contours and homogeneous enhancement of 40x32x25 mm, in intimate contact with medial pterygoid muscle, although there were no signs of infiltration, the rest of the edges being well delimited. Images characteristics look like a lymphoma, without being able to rule out other etiologies. MRI of the neck: It demostrates a diffuse thickening of right side of the soft palate that

Human herpesvirus 8-associated lymphoma mimicking cutaneous anaplastic large T-cell lymphoma in a patient with human immunodeficiency virus infection.

Science.gov (United States)

Li, Meng-Fang; Hsiao, Cheng-Hsiang; Chen, Yi-Lin; Huang, Wen-Ya; Lee, Yi-Hsuan; Huang, Hsien-Neng; Lien, Huang-Chun

2012-02-01

Primary effusion lymphoma, a human herpesvirus 8 (HHV8)-associated lymphoma, is uncommon, and it is usually seen in human immunodeficiency virus (HIV)-infected patients. It presents as a body cavity-based lymphomatous effusion, but several cases of the so-called solid primary effusion lymphoma presenting as solid tumors without associated lymphomatous effusion have been reported. They have similar clinical, histopathological and immunophenotypical features. Most of them have a B-cell genotype. This suggests the solid variant may represent a clinicopathological spectrum of primary effusion lymphoma. We report a case of HHV8-associated lymphoma histopathologically and immunophenotypically mimicking cutaneous anaplastic large cell lymphoma. The patient was a 31-year-old HIV-seropositive man presenting with skin nodules over his right thigh. Biopsy of the nodules showed anaplastic large cells infiltrating the dermis. These malignant cells strongly expressed CD3, CD30 and CD43. Cutaneous anaplastic large T-cell lymphoma was initially diagnosed, but further tests, including immunoreactivity for HHV8 protein and clonal rearrangements of immunoglobulin genes, confirmed the diagnosis of HHV8-associated B-cell lymphoma with aberrant T-cell marker expression. This case provides an example of solid primary effusion lymphoma mimicking cutaneous anaplastic large T-cell lymphoma and highlights the importance of HHV8 immunohistochemistry and molecular tests in the diagnosis of HHV8-associated lymphoma with a cutaneous presentation. Copyright © 2011 John Wiley & Sons A/S.

Study Identifies New Lymphoma Treatment Target

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NCI researchers have identified new therapeutic targets for diffuse large B-cell lymphoma. Drugs that hit these targets are under clinical development and the researchers hope to begin testing them in clinical trials of patients with DLBCL.

Primary Breast Mucosa-Associated Lymphoid Tissue (MALT Lymphoma Transformation to Diffuse Large B-cell Lymphoma: A Case Report

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Şerife Hülya Arslan

2012-09-01

Full Text Available Primary non-Hodgkin’s lymphoma (NHL of the breast constitutes 0.04%-0.53% of all malignancies and 2.2% of extra nodal lymphomas. In total, 7%-8% of all B-cell lymphomas are the mucosa-associated lymphoid tissue (MALT type, of which up to 50% of primary gastric MALT lymphoma. Herein we present a patient with breast MALT lymphoma that transformed to diffuse large B-cell lymphoma (DLBCL. A 69-year-old female presented with a mass on her left breast. Physical examination showed a 3 × 3-cm mass located 1 cm from the areola on the upper lateral quadrant of the breast at the 1 o’clock position, which was fixed and firm. Excisional biopsy was performed and pathologic examination of the specimen showed MALT lymphoma transformation to DLBCL. The patient was staged as II-EA. The rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP protocol was scheduled as treatment. Following 6 courses of R-CHOP, 2 additional courses of rituximab were administered. Positron emission tomography (PET-CT was done at the end of the treatment. PET showed that the patient was in complete remission. At the time this report was written, the patient was being followed-up at the outpatient clinic on a regular basis. Lymphoma of the breast is a rarity among malignant tumors of the breast. The most common type of lymphoma is DLBCL. Breast MALT lymphoma is extremely rare. Primary MALT lymphoma of the breast can transform from low grade to high grade and recurrence is possible; therefore, such patients should be monitored carefully for transformation.

The effect of steroid treatment on intracranial malignant lymphoma and its serial CT findings

International Nuclear Information System (INIS)

Takahashi, Yoshio; Ito, Kazunori; Mikami, Junichi; Ueda, Mikiya; Sato, Hiroyuki

1984-01-01

We treated 2 cases of intracranial malignant lymphoma presumably originating in the cerebellum and 1 case of intracranial malignant lymphoma presumably originating in the corpus callosum and ventricular ependium, by means of the administration of steroids. There resulted a marked shrinkage of the tumor shadow on CT. Though massive steroids are known to diminish the tumor shadow in CT images, steroids in ordinary doses induce such a shrinkage only rarely. The preoperative diagnosis of intracranial malignant lymphoma, therefore, seemed feasible if, besides plain CT, enhanced CT, and AG findings, the effect of steroid treatment on the CT image was taken into consideration. (author)

Splenic marginal zone lymphoma.

Science.gov (United States)

Piris, Miguel A; Onaindía, Arantza; Mollejo, Manuela

Splenic marginal zone lymphoma (SMZL) is an indolent small B-cell lymphoma involving the spleen and bone marrow characterized by a micronodular tumoral infiltration that replaces the preexisting lymphoid follicles and shows marginal zone differentiation as a distinctive finding. SMZL cases are characterized by prominent splenomegaly and bone marrow and peripheral blood infiltration. Cells in peripheral blood show a villous cytology. Bone marrow and peripheral blood characteristic features usually allow a diagnosis of SMZL to be performed. Mutational spectrum of SMZL identifies specific findings, such as 7q loss and NOTCH2 and KLF2 mutations, both genes related with marginal zone differentiation. There is a striking clinical variability in SMZL cases, dependent of the tumoral load and performance status. Specific molecular markers such as 7q loss, p53 loss/mutation, NOTCH2 and KLF2 mutations have been found to be associated with the clinical variability. Distinction from Monoclonal B-cell lymphocytosis with marginal zone phenotype is still an open issue that requires identification of precise and specific thresholds with clinical meaning. Copyright © 2016 Elsevier Ltd. All rights reserved.

Imaging of brain tumors

Energy Technology Data Exchange (ETDEWEB)

Gaensler, E H.L. [California Univ., San Francisco, CA (United States). Dept. of Radiology

1996-12-31

The contents are diagnostic approaches, general features of tumors -hydrocephalus, edema, attenuation and/or intensity value, hemorrhage, fat, contrast enhancement, intra-axial supratentorial tumors - tumors of glial origin, oligodendrogliomas, ependymomas, subependymomas, subependymal giant cell astrocytomas, choroid plexus papilloma; midline tumors - colloid cysts, craniopharyngiomas; pineal region tumors and miscellaneous tumors i.e. primary intracerebral lymphoma, primitive neuroectodermal tumors, hemangioblastomas; extraaxial tumors - meningiomas; nerve sheath tumors -schwannomas, epidermoids, dermoids, lipomas, arachnoid cysts; metastatic tumors (8 refs.).

Imaging of brain tumors

International Nuclear Information System (INIS)

Gaensler, E.H.L.

1995-01-01

The contents are diagnostic approaches, general features of tumors -hydrocephalus, edema, attenuation and/or intensity value, hemorrhage, fat, contrast enhancement, intra-axial supratentorial tumors - tumors of glial origin, oligodendrogliomas, ependymomas, subependymomas, subependymal giant cell astrocytomas, choroid plexus papilloma; midline tumors - colloid cysts, craniopharyngiomas; pineal region tumors and miscellaneous tumors i.e. primary intracerebral lymphoma, primitive neuroectodermal tumors, hemangioblastomas; extraaxial tumors - meningiomas; nerve sheath tumors -schwannomas, epidermoids, dermoids, lipomas, arachnoid cysts; metastatic tumors (8 refs.)

[Role of stem cell transplantation in treatment of primary cutaneous T‑cell lymphoma].

Science.gov (United States)

Stranzenbach, R; Theurich, S; Schlaak, M

2017-09-01

Within the heterogeneous group of cutaneous T‑cell lymphomas (CTCL) the therapeutic options for advanced and progressive forms are particularly limited. The therapeutic value of hematopoietic stem cell transplantation in CTCL was analyzed. A literature search using the keywords "hematopoietic stem cell transplantation" and "cutaneous T‑cell lymphoma" was performed in PubMed. Studies between 1990 and 2017 were taken into account. The studies identified were analyzed for relevance and being up to date. After reviewing the currently available literature no prospective randomized studies were found. Wu et al. showed a superiority of allogeneic transplantation in a comparison of autologous and allogeneic stem cell transplantation for cutaneous lymphoma. The graft-versus-lymphoma effect plays a significant role in a prolonged progression-free survival after allogeneic transplantation. By using a non-myeloablative conditioning regimen, stem cell transplantation can also be an option for elderly patients. The most extensive long-term data after allogeneic stem cell transplantation were reported by Duarte et al. in 2014. Autologous stem cell transplantation does not currently represent a therapeutic option, whereas allogeneic stem cell transplantation for advanced cutaneous T‑cell lymphoma, using a non-myeloablative conditioning scheme, does represent a therapeutic option. However, there is no consensus on the appropriate patients and the right timing. Morbidity and mortality of complications should be taken into account. Thus, this procedure is currently subject to an individual case decision.

Follicular Lymphoma Tregs Have a Distinct Transcription Profile Impacting Their Migration and Retention in the Malignant Lymph Node.

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Hristina Nedelkovska

Full Text Available We have previously shown that regulatory T cells (Tregs infiltrating follicular lymphoma lymph nodes are quantitatively and qualitatively different than those infiltrating normal and reactive nodes. To gain insight into how such Treg populations differ, we performed RNA sequence (RNAseq analyses on flow sorted Tregs from all three sources. We identify several molecules that could contribute to the observed increased suppressive capacity of follicular lymphoma nodal tregs, including upregulation of CTLA-4, IL-10, and GITR, all confirmed by protein expression. In addition, we identify, and confirm functionally, a novel mechanism by which Tregs target to and accumulate within a human tumor microenvironment, through the down regulation of S1PR1, SELL (L-selectin and CCR7, potentially resulting in greater lymph node retention. In addition we identify and confirm functionally the upregulation of the chemokine receptor CXCR5 as well as the secretion of the chemokines CXCL13 and IL-16 demonstrating the unique ability of the follicular derived Tregs to localize and accumulate within not only the malignant lymph node, but also localize and accumulate within the malignant B cell follicle itself. Such findings offer significant new insights into how follicular lymphoma nodal Tregs may contribute to the biology of follicular lymphoma and identify several novel therapeutic targets.

Helicobacter pylori-Negative Primary Rectal MALT Lymphoma: Complete Remission after Radiotherapy

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Takuma Okamura

2012-05-01

Full Text Available Rectal mucosa-associated lymphoid tissue (MALT lymphoma is a rare condition. Although the majority of patients undergo surgical resection, a definitive treatment for rectal MALT lymphoma has not yet been established. In the present study, we report the outcome of radiotherapy in 3 patients with rectal MALT lymphoma. Our cohort ranged from 56 to 65 years of age. The male/female ratio was 1:2, and all patients were in stage I (Lugano classification of the disease. Endoscopic findings revealed elevated lesions resembling submucosal tumors in 2 patients, and a sessile elevated lesion with a nodular surface in 1 patient. One of the 3 patients underwent magnifying endoscopy with crystal violet staining that demonstrated a type I pit pattern (Kudo’s classification lesion with a broad intervening area caused by the upthrust of the tumor from the submucosa. All patients tolerated radiotherapy at doses of 30 Gy without major complications and achieved complete remission. Follow-up ranged from 13 to 75 months (mean 51.0 months, revealing no recurrence of MALT lymphoma. As such, we propose radiotherapy to be a safe and effective means for treating rectal MALT lymphoma.

Anti-SEMA3A Antibody: A Novel Therapeutic Agent to Suppress GBM Tumor Growth.

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Lee, Jaehyun; Shin, Yong Jae; Lee, Kyoungmin; Cho, Hee Jin; Sa, Jason K; Lee, Sang-Yun; Kim, Seok-Hyung; Lee, Jeongwu; Yoon, Yeup; Nam, Do-Hyun

2017-11-10

Glioblastoma (GBM) is classified as one of the most aggressive and lethal brain tumor. Great strides have been made in understanding the genomic and molecular underpinnings of GBM, which translated into development of new therapeutic approaches to combat such deadly disease. However, there are only few therapeutic agents that can effectively inhibit GBM invasion in a clinical framework. In an effort to address such challenges, we have generated anti-SEMA3A monoclonal antibody as a potential therapeutic antibody against GBM progression. We employed public glioma datasets, Repository of Molecular Brain Neoplasia Data and The Cancer Genome Atlas, to analyze SEMA3A mRNA expression in human GBM specimens. We also evaluated for protein expression level of SEMA3A via tissue microarray (TMA) analysis. Cell migration and proliferation kinetics were assessed in various GBM patient-derived cells (PDCs) and U87-MG cell-line for SEMA3A antibody efficacy. GBM patient-derived xenograft (PDX) models were generated to evaluate tumor inhibitory effect of anti-SEMA3A antibody in vivo. By combining bioinformatics and TMA analysis, we discovered that SEMA3A is highly expressed in human GBM specimens compared to non-neoplastic tissues. We developed three different anti-SEMA3A antibodies, in fully human IgG form, through screening phage-displayed synthetic antibody library using a classical panning method. Neutralization of SEMA3A significantly reduced migration and proliferation capabilities of PDCs and U87-MG cell-line in vitro. In PDX models, treatment with anti-SEMA3A antibody exhibited notable tumor inhibitory effect through down-regulation of cellular proliferative kinetics and tumor-associated macrophages recruitment. In present study, we demonstrated tumor inhibitory effect of SEMA3A antibody in GBM progression and present its potential relevance as a therapeutic agent in a clinical framework.

Primary bone lymphoma: A report of two cases and review of the literature

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Singh Tejinder

2010-01-01

Full Text Available Primary bone lymphoma (PBL is an uncommon tumor accounting for approximately 4-5% of extra nodal lymphoma and less than 1% of all non-Hodgkin′s lymphoma. Disease may be complicated at presentation by pathological fracture or spinal cord compression. Diffuse large-B-cell lymphoma (DLBCL accounts for the majority of cases of PBL. Owing to its rarity, only a few retrospective studies have been published addressing the prognosis and treatment of primary bone lymphoma. In this paper, we report our experience with two cases of PBL treated with chemotherapy and radiotherapy and review literature to elucidate the optimal treatment of primary bone lymphoma.

Discovery and validation of the tumor-suppressive function of long noncoding RNA PANDA in human diffuse large B-cell lymphoma through the inactivation of MAPK/ERK signaling pathway.

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Wang, Yingjun; Zhang, Mingzhi; Xu, Huanan; Wang, Yifei; Li, Zhaoming; Chang, Yu; Wang, Xinhuan; Fu, Xiaorui; Zhou, Zhiyuan; Yang, Siyuan; Wang, Bei; Shang, Yufeng

2017-09-22

Diffuse large B-cell lymphoma (DLBCL) is one of the leading causes of cancer-related mortality, and responds badly to existing treatment. Thus, it is of urgent need to identify novel prognostic markers and therapeutic targets of DLBCL. Recent studies have shown that long non-coding RNAs (lncRNAs) play an important role in the development of cancer. By using the next generation HiSeq sequencing assay, we determined lncRNAs exhibiting differential expression between DLBCL patients and healthy controls. Then, RT-qPCR was performed for identification in clinical samples and cell materials, and lncRNA PANDA was verified to be down-regulated in DLBCL patients and have considerable diagnostic potential. In addition, decreased serum PANDA level was correlated to poorer clinical outcome and lower overall survival in DLBCL patients. Subsequently, we determined the experimental role of lncRNA PANDA in DLBCL progression. Luciferase reporter assay and chromatin immunoprecipitation assay suggested that lncRNA PANDA was induced by p53 and p53 interacts with the promoter region of PANDA. Cell functional assay further indicated that PANDA functioned as a tumor suppressor gene through the suppression of cell growth by a G0/G1 cell cycle arrest in DLBCL. More importantly, Cignal Signal Transduction Reporter Array and western blot assay showed that lncRNA PANDA inactivated the MAPK/ERK signaling pathway. In conclusion, our integrated approach demonstrates that PANDA in DLBCL confers a tumor suppressive function through inhibiting cell proliferation and silencing MAPK/ERK signaling pathway. Thus, PANDA may be a promising therapeutic target for patients with DLBCL.

Uroradiographic manifestations of Burkitt's lymphoma in children

International Nuclear Information System (INIS)

Fernbach, S.K.; Glass, R.B.

1986-01-01

The radiological studies of 18 children with biopsy proved Burkitt's lymphoma were analyzed retrospectively. Before therapy the genitourinary tract was evaluated in 15 children by excretory urography, sonography, computerized tomography and/or gallium citrate scintigraphy. Genitourinary abnormalities were detected in 9 children. Changes due to tumor included renal or ureteral displacement in 4 children, hydronephrosis in 3 and intraparenchymal masses in 4. Extrinsic compression of the bladder causing no compromise of function was seen in only 2 children. Gonadal involvement occurred in 2 boys and 1 girl. The modality of choice for evaluating the genitourinary tract in patients with Burkitt's lymphoma has been excretory urography. Since ultrasound and computerized tomography provide more direct information about tumor deposits within the kidney and retroperitoneum, either should be performed in this population before initiation of chemotherapy

Multi-gene epigenetic silencing of tumor suppressor genes in T-cell lymphoma cells; delayed expression of the p16 protein upon reversal of the silencing

DEFF Research Database (Denmark)

Nagasawa, T; Zhang, Q; Raghunath, P N

2006-01-01

To understand better T-cell lymphomagenesis, we examined promoter CpG methylation and mRNA expression of closely related genes encoding p16, p15, and p14 tumor suppressor genes in cultured malignant T-cells that were derived from cutaneous, adult type, and anaplastic lymphoma kinase (ALK)-express...

Enhanced Delivery of Gold Nanoparticles with Therapeutic Potential for Targeting Human Brain Tumors

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Etame, Arnold B.

The blood brain barrier (BBB) remains a major challenge to the advancement and application of systemic anti-cancer therapeutics into the central nervous system. The structural and physiological delivery constraints of the BBB significantly limit the effectiveness of conventional chemotherapy, thereby making systemic administration a non-viable option for the vast majority of chemotherapy agents. Furthermore, the lack of specificity of conventional systemic chemotherapy when applied towards malignant brain tumors remains a major shortcoming. Hence novel therapeutic strategies that focus both on targeted and enhanced delivery across the BBB are warranted. In recent years nanoparticles (NPs) have emerged as attractive vehicles for efficient delivery of targeted anti-cancer therapeutics. In particular, gold nanoparticles (AuNPs) have gained prominence in several targeting applications involving systemic cancers. Their enhanced permeation and retention within permissive tumor microvasculature provide a selective advantage for targeting. Malignant brain tumors also exhibit transport-permissive microvasculature secondary to blood brain barrier disruption. Hence AuNPs may have potential relevance for brain tumor targeting. However, the permeation of AuNPs across the BBB has not been well characterized, and hence is a potential limitation for successful application of AuNP-based therapeutics within the central nervous system (CNS). In this dissertation, we designed and characterized AuNPs and assessed the role of polyethylene glycol (PEG) on the physical and biological properties of AuNPs. We established a size-dependent permeation profile with respect to core size as well as PEG length when AuNPs were assessed through a transport-permissive in-vitro BBB. This study was the first of its kind to systematically examine the influence of design on permeation of AuNPs through transport-permissive BBB. Given the significant delivery limitations through the non

Analyses of susceptibility to radiation-induced tumors: Prkdc, a candidate modifier of lymphomas

International Nuclear Information System (INIS)

Mori, Nobuko; Okumoto, Masaaki; Nakao, Ren

2003-01-01

BALB/cHeA (BALB/c) mice are susceptible to radiation-induced lymphomas, while STS/A (STS) mice are resistant. To analyze the difference in susceptibility between these two strains of mice, we have performed 3 independent studies: 1) mapping of apoptosis susceptibility gene Rapopl (chromosome 16) and identification of Prkdc as a candidate modifier of apoptosis as well as lymphomas, 2) analysis of congenic lines for Lyr, a gene responsible for the lymphoma resistance of STS mice on chromosome 4, 3) genetic analyses of lymphoma susceptibility using a backcross [(BALB/c x STS)F 1 x STS]. Analysis of Rapopl congenic lines indicated a minor contribution of the STS allele at the Rapopl (Prkdc) locus to the lymphoma resistance of STS mice. On the other hand, homozygous STS alleles at Lyr had a substantial, but less potent, effect on radiation lymphomagenesis. Furthermore, there was no single marker where the potent resistance of the STS mice was achieved with the homozygous STS alleles. These results suggest potential involvement of another loci in the resistance of STS mice. (author)

Analysis of imaging findings and clinical abnormalities in patients with lymphoma

International Nuclear Information System (INIS)

Caldas, Flavio Augusto Ataliba; Montomiya, Carolina Tsumori; Silva, Helena Cristina da

2002-01-01

Computed tomography is currently the method of choice for the diagnostic and staging of lymphomas. Computed tomography enables accurate measurements of both tumor extent and volume and provides information that can be used to plan an appropriate strategy for the treatment. The purpose of the present article is to describe and analyze the chest and abdomen computed tomography and ultrasound findings in HIV-negative patients with lymphoma. Clinical abnormalities, such as the reason the patient sought medical assistance already showing evidence of lymphocytic disease (not yet diagnosed at this point) and the physical examination abnormalities seen on the first consultation were also studied. This study comprised 30 patients: 40% with non-Hodgkin lymphoma, 46,6% with Hodgkin lymphoma, 10% with Burkitt's lymphoma and 3,3% with lymphoblastic lymphoma. (author)

Effect of recombinant adenovirus encoding human p53 tumor suppressor gene (rAd-p53) on the growth and radiotherapeutic sensitivity of human lymphoma cell lines

International Nuclear Information System (INIS)

Yu Zeyang; Fan Wo; Li Dongqing; Zhu Ran; Wang Yongqing; Wu Jinchang

2008-01-01

Objective: To explore the inhibitory effect and radiation sensitization of recombinant adenovirus encoding human p53 tumor suppressor gene (rAd-p53) on human lymphoma cell lines. Methods: Human lymphoma cell lines Raji and Daudi were treated with rAd-p53, radiation therapy and combined treatment, respectively. The cell growth inhibition was assessed by MTT. The p53 protein expression was detected by Western blotting, and p53 mRNA was detected by BT-PCB. Results: The MTT results showed that the inhibitory effect and radiosensitivity enhancement of rAd-p53 on human lymphoma cell lines were not obvious [Raji: (27.5±4.1)%; Daudi: (28.1±1.6)%]. The results of Western blotting and BT-PCB showed that extrinsic p53 protein and p53 mRNA were expressed to some degree, but not at high-level. In addition, the results didn't demonstrate obvious radiosensitivity enhancement. Conclusions: The role of inhibition and radiosensitivity enhancement of rAd-p53 was not significant on human lymphoma cell lines. (authors)

Optimization of a therapeutic electromagnetic field (EMF) to retard breast cancer tumor growth and vascularity

OpenAIRE

Cameron, Ivan L; Markov, Marko S; Hardman, W Elaine

2014-01-01

Background This study provided additional data on the effects of a therapeutic electromagnetic field (EMF) device on growth and vascularization of murine 16/C mammary adenocarcinoma cells implanted in C3H/HeJ mice. Methods The therapeutic EMF device generated a defined 120 Hz semi sine wave pulse signal of variable intensity. Murine 16/C mammary adenocarcinoma tumor fragments were implanted subcutaneously between the scapulae of syngeneic C3H mice. Once the tumor grew to 100 mm3, daily EMF tr...

Characteristic mTOR activity in Hodgkin-lymphomas offers a potential therapeutic target in high risk disease – a combined tissue microarray, in vitro and in vivo study

International Nuclear Information System (INIS)

Márk, Ágnes; Kopper, László; Sebestyén, Anna; Hajdu, Melinda; Váradi, Zsófia; Sticz, Tamás Béla; Nagy, Noémi; Csomor, Judit; Berczi, Lajos; Varga, Viktória; Csóka, Monika

2013-01-01

effect of chemotherapeutic agents. Targeting mTOR activity may be a potential therapeutic tool in lymphomas. The presence of mTOR activity probably indicates that the inclusion of mTOR inhibition in the therapy of Hodgkin-lymphomas may be feasible and beneficial, especially when standard protocols are ineffective, and it may also allow dose reduction in order to decrease late treatment toxicity. Most likely, the combination of mTOR inhibitors with other agents will offer the highest efficiency for achieving the best clinical response

HAMLET kills tumor cells by an apoptosis-like mechanism--cellular, molecular, and therapeutic aspects.

Science.gov (United States)

Svanborg, Catharina; Agerstam, Helena; Aronson, Annika; Bjerkvig, Rolf; Düringer, Caroline; Fischer, Walter; Gustafsson, Lotta; Hallgren, Oskar; Leijonhuvud, Irene; Linse, Sara; Mossberg, Ann-Kristin; Nilsson, Hanna; Pettersson, Jenny; Svensson, Malin

2003-01-01

HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a protein-lipid complex that induces apoptosis-like death in tumor cells, but leaves fully differentiated cells unaffected. This review summarizes the information on the in vivo effects of HAMLET in patients and tumor models on the tumor cell biology, and on the molecular characteristics of the complex. HAMLET limits the progression of human glioblastomas in a xenograft model and removes skin papillomas in patients. This broad anti-tumor activity includes >40 different lymphomas and carcinomas and apoptosis is independent of p53 or bcl-2. In tumor cells HAMLET enters the cytoplasm, translocates to the perinuclear area, and enters the nuclei where it accumulates. HAMLET binds strongly to histones and disrupts the chromatin organization. In the cytoplasm, HAMLET targets ribosomes and activates caspases. The formation of HAMLET relies on the propensity of alpha-lactalbumin to alter its conformation when the strongly bound Ca2+ ion is released and the protein adopts the apo-conformation that exposes a new fatty acid binding site. Oleic acid (C18:1,9 cis) fits this site with high specificity, and stabilizes the altered protein conformation. The results illustrate how protein folding variants may be beneficial, and how their formation in peripheral tissues may depend on the folding change and the availability of the lipid cofactor. One example is the acid pH in the stomach of the breast-fed child that promotes the formation of HAMLET. This mechanism may contribute to the protective effect of breastfeeding against childhood tumors. We propose that HAMLET should be explored as a novel approach to tumor therapy.

Adhesion molecule profiles of B-cell non-Hodgkin's lymphomas in the leukemic phase

Directory of Open Access Journals (Sweden)

D.M. Matos

2006-10-01

Full Text Available We evaluated the expression of 10 adhesion molecules on peripheral blood tumor cells of 17 patients with chronic lymphocytic leukemia, 17 with mantle-cell lymphoma, and 13 with nodal or splenic marginal B-cell lymphoma, all in the leukemic phase and before the beginning of any therapy. The diagnosis of B-cell non-Hodgkin's lymphomas was based on cytological, histological, immunophenotypic, and molecular biology methods. The mean fluorescence intensity of the adhesion molecules in tumor cells was measured by flow cytometry of CD19-positive cells and differed amongst the types of lymphomas. Comparison of chronic lymphocytic leukemia and mantle-cell lymphoma showed that the former presented a higher expression of CD11c and CD49c, and a lower expression of CD11b and CD49d adhesion molecules. Comparison of chronic lymphocytic leukemia and marginal B-cell lymphoma showed that the former presented a higher expression of CD49c and a lower expression of CD11a, CD11b, CD18, CD49d, CD29, and CD54. Finally, comparison of mantle-cell lymphoma and marginal B-cell lymphoma showed that marginal B-cell lymphoma had a higher expression of CD11a, CD11c, CD18, CD29, and CD54. Thus, the CD49c/CD49d pair consistently demonstrated a distinct pattern of expression in chronic lymphocytic leukemia compared with mantle-cell lymphoma and marginal B-cell lymphoma, which could be helpful for the differential diagnosis. Moreover, the distinct profiles of adhesion molecules in these diseases may be responsible for their different capacities to invade the blood stream.

Prognostic value of defining the systemic tumor volume with FDG-PET in diffuse large b cell lymphoma

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Byun, Byung Hyun; Lim, Sang Moo; Cheon, Gi Jeong; Choi, Chang Woon; Kang, Hye Jin; Na, Im Il; Ryoo, Baek Yeol; Yang, Sung Hyun

2007-01-01

We measured the systemic tumor volume using FDG-PET in patients with diffuse large B cell lymphoma (DLBL). We also investigated its prognostic role, and compared it with that of other prognostic factors. FDG PET was performed in 38 newly diagnosed DLBL patients (20 men, 18 women, age 55.715.1 years) at pre-treatment of chemotherapy. Clinical staging of lymphoma was evaluated by Ann Arbor system. On each FDG PET scan, we acquired volume of interest (VOl) at the cut-off value of SUV=2.5 in every measurable tumor by the automatic edge detection software. According to the VOI, we measured the metabolic volume and mean SUV, and estimated volume-activity indexes (SUV Vol) as mean SUV times metabolic volume. And then, we calculated the summed metabolic volume (VOLsum) and summed SUV Vol (SUV Volsum) in every FDG PET scan. Maximum SUV of involved lesion (SUVmax) was also acquired on each FDG PET scan. Time to treatment failure (TTF) was compared among VOLsum (median), SUV Volsum (median), SUVmax (median), clinical stage, gender, age, LDH, and performance status-assigned response designations by Kaplan-Meier survival analysis. Initial stages of DLBL patients were stage I in 4, II in 14, III in 15, and IV in 4 by Ann Arbor system. Median follow up period was 15.5months, and estimated mean TTF was 22.3 months. Univariate analysis demonstrated that TTF is statistically significantly reduced in those with high VOLsum (>215.1cm2, p=0.004), high SUV Volsum (>1577.5, p=0.003), and increased LDH (p=0.036). TTF did not correlate with SUVmax (p=0.571), clinical stage (p=0.194), gender (p=0.549), and age (p=0.128), and performance status =2 (p=0.074). Multivariate analysis using VOLsum, SUV Volsum, LDH, and performance status demonstrated no statistically significant predictor of TTF (p>0.05). Systemic tumor volume measurement using FDG-PET is suggestive to be the significant prognostic factor in patients with DLBL

Prevention of Human Lymphoproliferative Tumor Formation in Ovarian Cancer Patient-Derived Xenografts

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Kristina A. Butler

2017-08-01

Full Text Available Interest in preclinical drug development for ovarian cancer has stimulated development of patient-derived xenograft (PDX or tumorgraft models. However, the unintended formation of human lymphoma in severe combined immunodeficiency (SCID mice from Epstein-Barr virus (EBV–infected human lymphocytes can be problematic. In this study, we have characterized ovarian cancer PDXs which developed human lymphomas and explore methods to suppress lymphoproliferative growth. Fresh human ovarian tumors from 568 patients were transplanted intraperitoneally in SCID mice. A subset of PDX models demonstrated atypical patterns of dissemination with mediastinal masses, hepatosplenomegaly, and CD45-positive lymphoblastic atypia without ovarian tumor engraftment. Expression of human CD20 but not CD3 supported a B-cell lineage, and EBV genomes were detected in all lymphoproliferative tumors. Immunophenotyping confirmed monoclonal gene rearrangements consistent with B-cell lymphoma, and global gene expression patterns correlated well with other human lymphomas. The ability of rituximab, an anti-CD20 antibody, to suppress human lymphoproliferation from a patient's ovarian tumor in SCID mice and prevent growth of an established lymphoma led to a practice change with a goal to reduce the incidence of lymphomas. A single dose of rituximab during the primary tumor heterotransplantation process reduced the incidence of CD45-positive cells in subsequent PDX lines from 86.3% (n = 117 without rituximab to 5.6% (n = 160 with rituximab, and the lymphoma rate declined from 11.1% to 1.88%. Taken together, investigators utilizing PDX models for research should routinely monitor for lymphoproliferative tumors and consider implementing methods to suppress their growth.

Testing of mechanisms of action of rituximab and clinical results in high-risk patients with aggressive CD20+ lymphoma

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Jezersek Novakovic, B.; Juznic Setina, T.; Vovk, M.; Kotnik, V.; Novakovic, S.

2007-01-01

Rituximab has been applied successfully in the treatment of indolent and aggressive CD20 positive B cell lymphomas, yet the exact in vivo mechanisms of its action have not been unambiguously explained. This study was therefore aimed to confirm the presumed major mechanisms of action of rituximab and concomitantly to assess the effectiveness of first-line chemo immunotherapy in high-risk patients with aggressive CD20 lymphomas. The activity of rituximab was tested in vitro on Raji and SU-DHL-4 cells using the cell proliferation assay and flow cytometry. In the clinical part of the study, 20 high-risk patients with aggressive CD 20 lymphomas were treated with R-CHOP. Only complement-mediated cytotoxicity was observed under the in vitro applied experimental conditions. Neither the direct apoptotic effect nor the antibody-dependent cell-mediated cytotoxicity was detected probably due to a too low concentration of rituximab and a too low ratio of cytotoxic lymphocytes to tumor cells. The treatment outcome in patients was excellent since complete remissions were achieved in 90% of poor-risk patients at the end of primary treatment and 80% of patients were disease-free at 18.5 months median observation period. According to our results, the complement-dependent cytotoxicity is an important mechanism of rituximab action in vitro. To achieve direct apoptosis, higher concentrations than 20 μg/ml of rituximab should be used, while for an effective antibody-dependent cell-mediated cytotoxicity, the ratio of cytotoxic lymphocytes to tumor cells should be higher than 1:1. In the high-risk patients with aggressive CD20 lymphomas, the addition of rituximab to CHOP substantially improves the therapeutic results. (author)

Therapeutic benefits in grid irradiation on Tomotherapy for bulky, radiation-resistant tumors.

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Narayanasamy, Ganesh; Zhang, Xin; Meigooni, Ali; Paudel, Nava; Morrill, Steven; Maraboyina, Sanjay; Peacock, Loverd; Penagaricano, Jose

2017-08-01

Spatially fractionated radiation therapy (SFRT or grid therapy) has proven to be effective in management of bulky tumors. The aim of this project is to study the therapeutic ratio (TR) of helical Tomotherapy (HT)-based grid therapy using linear-quadratic cell survival model. HT-based grid (or HT-GRID) plan was generated using a patient-specific virtual grid pattern of high-dose cylindrical regions using MLCs. TR was defined as the ratio of normal tissue surviving fraction (SF) under HT-GRID irradiation to an open debulking field of an equivalent dose that result in the same tumor cell SF. TR was estimated from DVH data on ten HT-GRID patient plans with deep seated, bulky tumor. Dependence of the TR values on radiosensitivity of the tumor cells and prescription dose was analyzed. The mean ± standard deviation (SD) of TR was 4.0 ± 0.7 (range: 3.1-5.5) for the 10 patients with single fraction maximum dose of 20 Gy to GTV assuming a tumor cell SF at 2 Gy (SF2 t ) value of 0·5. In addition, the mean ± SD of TR values for SF2 t values of 0.3 and 0.7 were found to be 1 ± 0.1 and 18.0 ± 5.1, respectively. Reducing the prescription dose to 15 and 10 Gy lowered the respective TR values to 2.0 ± 0.2 and 1.2 ± 0.04 for a SF2 t value of 0.5. HT-GRID therapy demonstrates a significant therapeutic advantage over uniform dose from an open field irradiation for the same tumor cell kill. TR increases with the radioresistance of the tumor cells and with prescription dose.

Management of untreated advanced stage follicular lymphoma: Role of patient discernment.

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Umakanthan, Jayadev Manikkam; Lunning, Mathew A

2018-03-01

Follicular lymphoma is the most common indolent non-Hodgkin lymphoma. Advanced stage disease is common at diagnosis. The timing of treatment for follicular lymphoma is best approached by considering the combination of presence or absence of symptoms along with estimation of tumor burden. Upfront treatment strategies should take into initial presentation variables, pace of disease progression and goals of care after discussion with the patient. Treatment approaches remain diverse and patient discernment is paramount. Copyright © 2017 Elsevier Ltd. All rights reserved.

Autoimmune/Inflammatory Arthritis Associated Lymphomas: Who Is at Risk?

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Sujani Yadlapati

2016-01-01

Full Text Available Specific autoimmune and inflammatory rheumatic diseases have been associated with an increased risk of malignant lymphomas. Conditions such as rheumatoid arthritis (RA, primary Sjögren’s syndrome (pSS, systemic lupus erythematosus (SLE, dermatomyositis, and celiac disease have been consistently linked to malignant lymphomas. Isolated cases of lymphomas associated with spondyloarthropathies and autoinflammatory diseases have also been reported. Direct association between autoimmunity and lymphomagenesis has been reinforced by large epidemiological studies. It is still uncertain whether disease specific determinants or phenotypic or treatment related characteristics increase likelihood of lymphomagenesis in these patients. For example, recent literature has indicated a positive correlation between severity of inflammation and risk of lymphomas among RA and Sjögren’s syndrome patients. It is also debated whether specific lymphoma variants are more commonly seen in accordance with certain chronic autoimmune arthritis. Previous studies have revealed a higher incidence of diffuse large B-cell lymphomas in RA and SLE patients, whereas pSS has been linked with increased risk of mucosa-associated lymphoid tissue lymphoma. This review summarizes recent literature evaluating risk of lymphomas in arthritis patients and disease specific risk determinants. We also elaborate on the association of autoimmune arthritis with specific lymphoma variants along with genetic, environmental, and therapeutic risk factors.

MYC Immunohistochemistry to Identify MYC-Driven B-Cell Lymphomas in Clinical Practice.

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Kluk, Michael J; Ho, Caleb; Yu, Hongbo; Chen, Benjamin J; Neuberg, Donna S; Dal Cin, Paola; Woda, Bruce A; Pinkus, Geraldine S; Rodig, Scott J

2016-02-01

Immunohistochemistry with anti-MYC antibody (MYC IHC) detects MYC protein in fixed samples of aggressive B-cell lymphomas and, according to the number of positive staining tumor nuclei, facilitates tumor subclassification, predicts underlying MYC rearrangements, and stratifies patient outcome. We aimed to determine the performance of MYC IHC in clinical practice. We reviewed MYC IHC performed on control specimens and 256 aggressive B-cell lymphomas and compared clinically reported IHC scores with experts' review. Control tissues showed less than 5% variation in daily IHC staining. Reported and expert IHC scores were well correlated (r = 0.86) with an SD of 14.2%. Reported IHC scores 30% or less and 70% or more were accurate (94.5%) compared with experts in categorizing tumors as "MYC IHC-Low" and "MYC IHC-High," respectively, but scores 40% to 60% were not (60.3%). The mean IHC score among lymphomas with MYC rearrangements was 80%, but with a large range of scores (20%-100%). There was no statistically significant association between IHC score and MYC copy number. Under optimal conditions, clinically reported MYC IHC scores are concordant with expert scores within 15%. MYC IHC does not capture all B-cell lymphomas with MYC rearrangements, however. MYC IHC and MYC fluorescence in situ hybridization are both recommended to identify MYC-driven B-cell lymphomas. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Color-Coded Imaging of Syngeneic Orthotopic Malignant Lymphoma Interacting with Host Stromal Cells During Metastasis.

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Matsumoto, Takuro; Suetsugu, Atsushi; Hasegawa, Kosuke; Nakamura, Miki; Aoki, Hitomi; Kunisada, Takahiro; Tsurumi, Hisashi; Shimizu, Masahito; Hoffman, Robert M

2016-04-01

The EL4 cell line was previously derived from a lymphoma induced in a C57/BL6 mouse by 9,10-dimethyl-1,2-benzanthracene. In a previous study, EL4 lymphoma cells expressing red fluorescent protein (EL4-RFP) were established and injected into the tail vein of C57/BL6 green fluorescent protein (GFP) transgenic mice. Metastasis was observed at multiple sites which were also enriched with host GFP-expressing stromal cells. In the present study, our aim was to establish an orthotopic model of EL4-RFP. In the present study, EL4-RFP lymphoma cells were injected in the spleen of C57/BL6 GFP transgenic mice as an orthotopic model of lymphoma. Resultant primary tumor and metastases were imaged with the Olympus FV1000 scanning laser confocal microscope. EL4-RFP metastasis was observed 21 days later. EL4-RFP tumors in the spleen (primary injection site), liver, supra-mediastinum lymph nodes, abdominal lymph nodes, bone marrow, and lung were visualized by color-coded imaging. EL4-RFP metastases in the liver, lymph nodes, and bone marrow in C57/BL6 GFP mice were rich in GFP stromal cells such as macrophages, fibroblasts, dendritic cells, and normal lymphocytes derived from the host animal. Small tumors were observed in the spleen, which were rich in host stromal cells. In the lung, no mass formation of lymphoma cells occurred, but lymphoma cells circulated in lung peripheral blood vessels. Phagocytosis of EL4-RFP lymphoma cells by macrophages, as well as dendritic cells and fibroblasts, were observed in culture. Color-coded imaging of the lymphoma microenvironment suggests an important role of stromal cells in lymphoma progression and metastasis. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Conditional expression of CD44 isoforms in lymphoma cells: influence on hyaluronate binding and tumor growth

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Fu, J.

2002-03-01

CD44 describes a family of surface proteins consisting of many isoforms due to alternative splice of ten 'variant' exons. Members of this family are involved in various processes including hematopoiesis, lymphocyte activation and homing, limb development, wound healing and tumor progression. Clinically, CD44 has been shown to be a prognostic factor for several human cancers. To answer the question which isoform might be relevant for tumor progression and to gain an insight into the mechanism of its function, I established transfectants of the LB lymphoma cell line in which the expression of four CD44 isoforms, namely CD44v3-10, CD44v4-10, CD44v8-10 and CD44s, was controlled by the Tet-off promoter. In the presence of Doxycycline, the expression was repressed. Removal of Doxycycline switched on expression and the maximal CD44 amount was obtained within two days. The transfectants were characterized regarding their ability to bind to the extracellular matrix component hyaluronate (HA). Overexpression of all four CD44 isoforms conferred the ability to bind HA on LB cells. Other glycosaminoglycans (GAGs) were bound in an isotype-specific fashion. CD44v3-10, CD44v4-10 and CD44v8-10 showed high binding affinity to chondroitin A, B and C, and low affinity to heparin, heparan sulfate and keratan sulfate. CD44s could not bind to these GAGs. Among these three variants, the binding ability of CD44v3-10 was the strongest. CD44 clustering seemed to play a crucial role for HA binding. Both CD44s and CD44v8-10 formed reduction-sensitive complexes in LB cells. The complexes are homooligomers or heterooligomers composed of different isoforms. Cys286 in CD44 transmember domain was not responsible for the formation of reduction-sensitive oligomer or for the enhanced HA binding in LB cell line. Using a conditional dimerization system the requirement of CD44 oligomerization for HA binding was directly demonstrated. The induction of oligomerization increased HA binding

Conditional expression of CD44 isoforms in lymphoma cells: influence on hyaluronate binding and tumor growth

International Nuclear Information System (INIS)

Fu, J.

2002-03-01

CD44 describes a family of surface proteins consisting of many isoforms due to alternative splice of ten 'variant' exons. Members of this family are involved in various processes including hematopoiesis, lymphocyte activation and homing, limb development, wound healing and tumor progression. Clinically, CD44 has been shown to be a prognostic factor for several human cancers. To answer the question which isoform might be relevant for tumor progression and to gain an insight into the mechanism of its function, I established transfectants of the LB lymphoma cell line in which the expression of four CD44 isoforms, namely CD44v3-10, CD44v4-10, CD44v8-10 and CD44s, was controlled by the Tet-off promoter. In the presence of Doxycycline, the expression was repressed. Removal of Doxycycline switched on expression and the maximal CD44 amount was obtained within two days. The transfectants were characterized regarding their ability to bind to the extracellular matrix component hyaluronate (HA). Overexpression of all four CD44 isoforms conferred the ability to bind HA on LB cells. Other glycosaminoglycans (GAGs) were bound in an isotype-specific fashion. CD44v3-10, CD44v4-10 and CD44v8-10 showed high binding affinity to chondroitin A, B and C, and low affinity to heparin, heparan sulfate and keratan sulfate. CD44s could not bind to these GAGs. Among these three variants, the binding ability of CD44v3-10 was the strongest. CD44 clustering seemed to play a crucial role for HA binding. Both CD44s and CD44v8-10 formed reduction-sensitive complexes in LB cells. The complexes are homooligomers or heterooligomers composed of different isoforms. Cys286 in CD44 transmember domain was not responsible for the formation of reduction-sensitive oligomer or for the enhanced HA binding in LB cell line. Using a conditional dimerization system the requirement of CD44 oligomerization for HA binding was directly demonstrated. The induction of oligomerization increased HA binding. Finally, I

White-matter abnormalities in unirradiated patients cured of primary central nervous system lymphoma

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Kim, L.; Hochberg, F.H.; Shaeffer, P.

2000-01-01

On MRI, primary brain tumors are commonly seen as contrast-enhancing masses surrounded by areas of abnormal signal on T2-weighted images. Following successful treatment tumors may no longer show contrast enhancement. The residual abnormalities are assumed to be represent ''edema'' and infiltrating tumor cells. We report nine patients with primary lymphoma of the central nervous system who had complete responses to intravenous methotrexate, but did not receive intrathecal chemotherapy or cranial irradiation. After complete resolution of contrast-enhancing lesions, persistent abnormalities on T2-weighted images in the region of prior tumor were initially assumed to reflect residual viable tumor. As they remained unchanged for years, however, this may not hold true in the cases in which primary central nervous system lymphoma responds to chemotherapy alone. (orig.)

Endogenous pyrogen production by Hodgkin's disease and human histiocytic lymphoma cell lines in vitro.

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Bodel, P; Ralph, P; Wenc, K; Long, J C

1980-01-01

Fever not explained by infection may occur in patients with malignant lymphoma presumably caused by a release of endogenous pyrogen. Although pyrogen has been found in some tumors with a mixed cell population, production of endogenous pyrogen by the neoplastic cells has not been demonstrated. This report documents the apparently spontaneous synthesis and release of such pyrogen by two human tumor cell lines derived from patients with Hodgkin's disease and histiocytic lymphoma. The endogenous ...

Genetic polymorphisms and tissue expression of interleukin-22 associated with risk and therapeutic response of gastric mucosa-associated lymphoid tissue lymphoma

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Liao, F; Hsu, Y-C; Kuo, S-H; Yang, Y-C; Chen, J-P; Hsu, P-N; Lin, C-W; Chen, L-T; Cheng, A-L; Fann, C S J; Lin, J-T; Wu, M-S

2014-01-01

Chronic Helicobacter pylori-stimulated immune reactions determine the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. We aimed to explore the genetic predisposition to this lymphoma and its clinical implication. A total of 68 patients and 140 unrelated controls were genotyped for 84 single-nucleotide polymorphisms in genes encoding cytokines, chemokines and related receptors that play important roles in T cell-mediated gastrointestinal immunity. Five genotypes in IL-22, namely CC at rs1179246, CC at rs2227485, AA at rs4913428, AA at rs1026788 and TT at rs7314777, were associated with disease susceptibility. The former four genotypes resided in the same linkage disequilibrium block (r 2 =0.99) that conferred an approximately threefold higher risk. In vitro experiments demonstrated that co-culturing peripheral mononuclear cells or CD4 + T cells with H. pylori stimulated the secretion of interleukin-22 (IL-22), and that IL-22 induced the expression of antimicrobial proteins, RegIIIα and lipocalin-2, in gastric epithelial cells. Furthermore, patients with gastric tissue expressing IL-22 were more likely to respond to H. pylori eradication (14/22 vs 4/19, P<0.006). We conclude that susceptibility of gastric MALT lymphoma is influenced by genetic polymorphisms in IL-22, the product of which is involved in mucosal immunity against H. pylori and associated with tumor response to H. pylori eradication

Targeting Malignant Brain Tumors with Antibodies

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Rok Razpotnik

2017-09-01

Full Text Available Antibodies have been shown to be a potent therapeutic tool. However, their use for targeting brain diseases, including neurodegenerative diseases and brain cancers, has been limited, particularly because the blood–brain barrier (BBB makes brain tissue hard to access by conventional antibody-targeting strategies. In this review, we summarize new antibody therapeutic approaches to target brain tumors, especially malignant gliomas, as well as their potential drawbacks. Many different brain delivery platforms for antibodies have been studied such as liposomes, nanoparticle-based systems, cell-penetrating peptides (CPPs, and cell-based approaches. We have already shown the successful delivery of single-chain fragment variable (scFv with CPP as a linker between two variable domains in the brain. Antibodies normally face poor penetration through the BBB, with some variants sufficiently passing the barrier on their own. A “Trojan horse” method allows passage of biomolecules, such as antibodies, through the BBB by receptor-mediated transcytosis (RMT. Such examples of therapeutic antibodies are the bispecific antibodies where one binding specificity recognizes and binds a BBB receptor, enabling RMT and where a second binding specificity recognizes an antigen as a therapeutic target. On the other hand, cell-based systems such as stem cells (SCs are a promising delivery system because of their tumor tropism and ability to cross the BBB. Genetically engineered SCs can be used in gene therapy, where they express anti-tumor drugs, including antibodies. Different types and sources of SCs have been studied for the delivery of therapeutics to the brain; both mesenchymal stem cells (MSCs and neural stem cells (NSCs show great potential. Following the success in treatment of leukemias and lymphomas, the adoptive T-cell therapies, especially the chimeric antigen receptor-T cells (CAR-Ts, are making their way into glioma treatment as another type of cell

Open questions in the management of nodular lymphocyte predominant hodgkin lymphoma.

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Tyran, Marguerite; Gonzague, Laurence; Bouabdallah, Reda; Resbeut, Michel

2014-01-01

Localized Nodular Lymphocyte Predominant Hodgkin Lymphoma is a rare disease with an overall good prognosis but frequent late relapses. Due to it's rarity there is no standard therapeutic approach and pathological diagnosis may be hard. In this paper we discuss the technical aspects of the radiation therapy and histological issues. The new fields reductions proposed for classical Hodgkin lymphoma cannot be applied to early stages Nodular Lymphocyte Predominant Hodgkin lymphomas which are usually treated with radiation therapy without systemic chemotherapy.

Enhanced therapeutic effect of APAVAC immunotherapy in combination with dose-intense chemotherapy in dogs with advanced indolent B-cell lymphoma.

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Marconato, L; Stefanello, D; Sabattini, S; Comazzi, S; Riondato, F; Laganga, P; Frayssinet, P; Pizzoni, S; Rouquet, N; Aresu, L

2015-09-22

The aim of this non-randomized controlled trial was to compare time to progression (TTP), lymphoma-specific survival (LSS), and safety of an autologous vaccine (consisting of hydroxyapatite ceramic powder and Heat Shock Proteins purified from the dogs' tumors, HSPPCs-HA) plus chemotherapy versus chemotherapy alone in dogs with newly diagnosed, clinically advanced, histologically confirmed, multicentric indolent B-cell lymphoma. The vaccine was prepared from dogs' resected lymph nodes and administered as an intradermal injection. Forty-five client-owned dogs were enrolled: 20 dogs were treated with dose-intense chemotherapy, and 25 received concurrent immunotherapy. Both treatment arms were well tolerated, with no exacerbated toxicity in dogs also receiving the vaccine. TTP was significantly longer for dogs treated with chemo-immunotherapy versus those receiving chemotherapy only (median, 209 versus 85 days, respectively, P=0.015). LSS was not significantly different between groups: dogs treated with chemo-immunotherapy had a median survival of 349 days, and those treated with chemotherapy only had a median survival of 200 days (P=0.173). Among vaccinated dogs, those mounting an immune response had a significantly longer TTP and LSS than those with no detectable response (P=0.012 and P=0.003, respectively). Collectively these results demonstrate that vaccination with HSPPCs-HA may produce clinical benefits with no increased toxicity, thereby providing a strategy for enhancing chemotherapy in dogs with advanced indolent lymphoma. Copyright © 2015 Elsevier Ltd. All rights reserved.

Primary mantle cell lymphoma of tonsil: Case report

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Knežević Snežana B.

2017-01-01

Full Text Available Introduction: Mantle cell lymphoma is rare type of the mature B cell lymphoma. It includes 4% - 6% of all Non Hodgkin's Lymphomas. Compared to the other subtypes of lymphoma it develops more often in older men, and the median age of patients is 65 years. Primary tonsillar lymphoma accounts for less than 1% of head and neck malignancies. Method: Data obtained from medical records of the patient. Objective: Emphasize the importance of early and accurate diagnosis and early treatment of malignant diseases. Case report: Patient RP, 63 years old, presents with difficult swallowing, hoarseness, enlarged tonsils, snoring. Left tonsil almost sets into the right tonsillar vine, displaces the uvula and covers the isthmus. Respiratory sound is normal, with rhythmic action of the heart and soft abdomen. Good general condition. Echo: enlarged and actively altered lymph glands of the middle right jugular chain, the largest 148x77 mm, on the left side lymph nodes are enlarged, the largest is 143x72 mm. Echo of the abdomen inconspicuous. Lab: WBC 5.9, RBC 5.2, Hb 152, Hct 0.44, SE 10, CK 129, LDH 331, CRP 4.6, ALP 61, fibrinogen 2.4, Ca2+ 2.3, phosphate 0.8; BK, HCV, HBsAg, EB, HIV negative. X-ray of the chest inconspicuous. Admitted to the hematology department of the General Hospital. PH: Immunoproliferative disease. Immunohistochemistry, at the institute of Pathology: IHH CK AE1-AE3, PAX5 +, CD20 +, CD3, bcl2 +, bcl6-, CyklinD1 +, CD23-, CD43 +, MUM1 - / +, Ki67 + in about 20% of the tumor cells. Morphological and immunohistochemical findings: Mantle cell lymphoma. MSCD of the neck, chest and upper abdomen: Left tonsil diameter is 28x32 mm and length is 36mm, with lobular contour and heterogeneous structure, asymmetrically narrowing lumen of the airways to 7 mm. pathologically enlarged submandibular and par jugular lymph nodes (10-15 mm diameter on the left. There were no pathological findings in the lung parenchyma. Abdominal and retroperitoneal lymph nodes

Primary parotid gland lymphoma: a case report

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Paraskevas Katsaronis

2011-08-01

Full Text Available Abstract Introduction Mucosa associated lymphoid tissue lymphomas are the most common lymphomas of the salivary glands. The benign lymphoepithelial lesion is also a lymphoproliferative disease that develops in the parotid gland. In the present case report, we describe one case of benign lymphoepithelial lesion with a subsequent low transformation to grade mucosa associated lymphoid tissue lymphoma appearing as a cystic mass in the parotid gland. Case presentation A 78-year-old Caucasian female smoker was referred to our clinic with a non-tender left facial swelling that had been present for approximately three years. The patient underwent resection of the left parotid gland with preservation of the left facial nerve through a preauricular incision. The pathology report was consistent with a low-grade marginal-zone B-cell non-Hodgkin lymphoma (mucosa associated lymphoid tissue lymphoma following benign lymphoepithelial lesion of the gland. Conclusions Salivary gland mucosa associated lymphoid tissue lymphoma should be considered in the differential diagnosis of cystic or bilateral salivary gland lesions. Parotidectomy is recommended in order to treat the tumor and to ensure histological diagnosis for further follow-up planning. Radiotherapy and chemotherapy should be considered in association with surgery in disseminated forms or after removal.

Exosomes as a tumor immune escape mechanism: possible therapeutic implications

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Hanley Harold H

2008-07-01

Full Text Available Abstract Advances in cancer therapy have been substantial in terms of molecular understanding of disease mechanisms, however these advances have not translated into increased survival in the majority of cancer types. One unsolved problem in current cancer therapeutics is the substantial immune suppression seen in patients. Conventionally, investigations in this area have focused on antigen-nonspecific immune suppressive molecules such as cytokines and T cell apoptosis inducing molecules such as Fas ligand. More recently, studies have demonstrated nanovesicle particles termed exosomes are involved not only in stimulation but also inhibition of immunity in physiological conditions. Interestingly, exosomes secreted by cancer cells have been demonstrated to express tumor antigens, as well as immune suppressive molecules such as PD-1L and FasL. Concentrations of exosomes from plasma of cancer patients have been associated with spontaneous T cell apoptosis, which is associated in some situations with shortened survival. In this paper we place the "exosome-immune suppression" concept in perspective of other tumor immune evasion mechanisms. We conclude by discussing a novel therapeutic approach to cancer immune suppression by extracorporeal removal of exosomes using hollow fiber filtration technology

Texture-based classification of different gastric tumors at contrast-enhanced CT

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Ba-Ssalamah, Ahmed, E-mail: ahmed.ba-ssalamah@meduniwien.ac.at [Department of Radiology, Medical University of Vienna (Austria); Muin, Dina; Schernthaner, Ruediger; Kulinna-Cosentini, Christiana; Bastati, Nina [Department of Radiology, Medical University of Vienna (Austria); Stift, Judith [Department of Pathology, Medical University of Vienna (Austria); Gore, Richard [Department of Radiology, University of Chicago Pritzker School of Medicine, Chicago, IL (United States); Mayerhoefer, Marius E. [Department of Radiology, Medical University of Vienna (Austria)

2013-10-01

Purpose: To determine the feasibility of texture analysis for the classification of gastric adenocarcinoma, lymphoma, and gastrointestinal stromal tumors on contrast-enhanced hydrodynamic-MDCT images. Materials and methods: The arterial phase scans of 47 patients with adenocarcinoma (AC) and a histologic tumor grade of [AC-G1, n = 4, G1, n = 4; AC-G2, n = 7; AC-G3, n = 16]; GIST, n = 15; and lymphoma, n = 5, and the venous phase scans of 48 patients with AC-G1, n = 3; AC-G2, n = 6; AC-G3, n = 14; GIST, n = 17; lymphoma, n = 8, were retrospectively reviewed. Based on regions of interest, texture analysis was performed, and features derived from the gray-level histogram, run-length and co-occurrence matrix, absolute gradient, autoregressive model, and wavelet transform were calculated. Fisher coefficients, probability of classification error, average correlation coefficients, and mutual information coefficients were used to create combinations of texture features that were optimized for tumor differentiation. Linear discriminant analysis in combination with a k-nearest neighbor classifier was used for tumor classification. Results: On arterial-phase scans, texture-based lesion classification was highly successful in differentiating between AC and lymphoma, and GIST and lymphoma, with misclassification rates of 3.1% and 0%, respectively. On venous-phase scans, texture-based classification was slightly less successful for AC vs. lymphoma (9.7% misclassification) and GIST vs. lymphoma (8% misclassification), but enabled the differentiation between AC and GIST (10% misclassification), and between the different grades of AC (4.4% misclassification). No texture feature combination was able to adequately distinguish between all three tumor types. Conclusion: Classification of different gastric tumors based on textural information may aid radiologists in establishing the correct diagnosis, at least in cases where the differential diagnosis can be narrowed down to two

Texture-based classification of different gastric tumors at contrast-enhanced CT

International Nuclear Information System (INIS)

Ba-Ssalamah, Ahmed; Muin, Dina; Schernthaner, Ruediger; Kulinna-Cosentini, Christiana; Bastati, Nina; Stift, Judith; Gore, Richard; Mayerhoefer, Marius E.

2013-01-01

Purpose: To determine the feasibility of texture analysis for the classification of gastric adenocarcinoma, lymphoma, and gastrointestinal stromal tumors on contrast-enhanced hydrodynamic-MDCT images. Materials and methods: The arterial phase scans of 47 patients with adenocarcinoma (AC) and a histologic tumor grade of [AC-G1, n = 4, G1, n = 4; AC-G2, n = 7; AC-G3, n = 16]; GIST, n = 15; and lymphoma, n = 5, and the venous phase scans of 48 patients with AC-G1, n = 3; AC-G2, n = 6; AC-G3, n = 14; GIST, n = 17; lymphoma, n = 8, were retrospectively reviewed. Based on regions of interest, texture analysis was performed, and features derived from the gray-level histogram, run-length and co-occurrence matrix, absolute gradient, autoregressive model, and wavelet transform were calculated. Fisher coefficients, probability of classification error, average correlation coefficients, and mutual information coefficients were used to create combinations of texture features that were optimized for tumor differentiation. Linear discriminant analysis in combination with a k-nearest neighbor classifier was used for tumor classification. Results: On arterial-phase scans, texture-based lesion classification was highly successful in differentiating between AC and lymphoma, and GIST and lymphoma, with misclassification rates of 3.1% and 0%, respectively. On venous-phase scans, texture-based classification was slightly less successful for AC vs. lymphoma (9.7% misclassification) and GIST vs. lymphoma (8% misclassification), but enabled the differentiation between AC and GIST (10% misclassification), and between the different grades of AC (4.4% misclassification). No texture feature combination was able to adequately distinguish between all three tumor types. Conclusion: Classification of different gastric tumors based on textural information may aid radiologists in establishing the correct diagnosis, at least in cases where the differential diagnosis can be narrowed down to two

Low GILT expression is associated with poor patient survival in diffuse large B-cell lymphoma

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Hannah ePhipps-Yonas

2013-12-01

Full Text Available The MHC class II-restricted antigen processing pathway presents antigenic peptides acquired in the endocytic route for the activation of CD4+ T cells. Multiple cancers express MHC class II, which may influence the anti-tumor immune response and patient outcome. Low MHC class II expression is associated with poor survival in diffuse large B-cell lymphoma (DLBCL, the most common form of aggressive non-Hodgkin lymphoma. Therefore, we investigated whether gamma-interferon-inducible lysosomal thiol reductase (GILT, an upstream component of the MHC class II-restricted antigen processing pathway that is not regulated by the transcription factor class II transactivator, may be important in DLBCL biology. GILT reduces protein disulfide bonds in the endocytic compartment, exposing additional epitopes for MHC class II binding and facilitating antigen presentation. In each of four independent gene expression profiling cohorts with a total of 585 DLBCL patients, low GILT expression was significantly associated with poor overall survival. In contrast, low expression of a classical MHC class II gene, HLA-DRA, was associated with poor survival in one of four cohorts. The association of low GILT expression with poor survival was independent of established clinical and molecular prognostic factors, the International Prognostic Index and the cell of origin classification, respectively. Immunohistochemical analysis of GILT expression in 96 DLBCL cases demonstrated variation in GILT protein expression within tumor cells which correlated strongly with GILT mRNA expression. These studies identify a novel association between GILT expression and clinical outcome in lymphoma. Our findings underscore the role of antigen processing in DLBCL and suggest that molecules targeting this pathway warrant investigation as potential therapeutics.

Transcatheter Arterial Embolization for Gastrointestinal Bleeding Secondary to Gastrointestinal Lymphoma

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Zheng, Lin [Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, Department of Radiology (China); Shin, Ji Hoon, E-mail: jhshin@amc.seoul.kr; Han, Kichang; Tsauo, Jiaywei; Yoon, Hyun-Ki; Ko, Gi-Young [University of Ulsan, College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology (Korea, Republic of); Shin, Jong-Soo [Kyunghee University, College of Medicine, Kangdong Kyunghee University Hospital, Department of Radiology (Korea, Republic of); Sung, Kyu-Bo [University of Ulsan, College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology (Korea, Republic of)

2016-11-15

PurposeTo evaluate the effectiveness of transcatheter arterial embolization (TAE) for gastrointestinal (GI) bleeding caused by GI lymphoma.Materials and MethodsThe medical records of 11 patients who underwent TAE for GI bleeding caused by GI lymphoma between 2001 and 2015 were reviewed retrospectively.ResultsA total of 20 TAE procedures were performed. On angiography, contrast extravasation, and both contrast extravasation and tumor staining were seen in 95 % (19/20) and 5 % (1/20) of the procedures, respectively. The most frequently embolized arteries were jejunal (n = 13) and ileal (n = 5) branches. Technical and clinical success rates were 100 % (20/20) and 27 % (3/11), respectively. The causes of clinical failure in eight patients were rebleeding at new sites. In four patients who underwent repeat angiography, the bleeding focus was new each time. Three patients underwent small bowel resection due to rebleeding after one (n = 2) or four (n = 1) times of TAEs. Another two patients underwent small bowel resection due to small bowel ischemia/perforation after three or four times of TAEs. The 30-day mortality rate was 18 % due to hypovolemic shock (n = 1) and multiorgan failure (n = 1).ConclusionAngiogram with TAE shows limited therapeutic efficacy to manage GI lymphoma-related bleeding due to high rebleeding at new sites. Although TAE can be an initial hemostatic measure, surgery should be considered for rebleeding due to possible bowel ischemic complication after repeated TAE procedures.

Antineoplastic activity of the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine in anaplastic large cell lymphoma

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Hassler, Melanie R.; Klisaroska, Aleksandra; Kollmann, Karoline; Steiner, Irene; Bilban, Martin; Schiefer, Ana-Iris; Sexl, Veronika; Egger, Gerda

2012-01-01

DNA methylation is an epigenetic mechanism establishing long-term gene silencing during development and cell commitment, which is maintained in subsequent cell generations. Aberrant DNA methylation is found at gene promoters in most cancers and can lead to silencing of tumor suppressor genes. The DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine (5-aza-CdR) is able to reactivate genes silenced by DNA methylation and has been shown to be a very potent epigenetic drug in several hematological malignancies. In this report, we demonstrate that 5-aza-CdR exhibits high antineoplastic activity against anaplastic large cell lymphoma (ALCL), a rare CD30 positive non-Hodgkin lymphoma of T-cell origin. Low dose treatment of ALCL cell lines and xenografted tumors causes apoptosis and cell cycle arrest in vitro and in vivo. This is also reflected in genome-wide expression analyses, where genes related to apoptosis and cell death are amongst the most affected targets of 5-aza-CdR. Furthermore, we observed demethylation and re-expression of p16INK4A after drug administration and senescence associated β-galactosidase activity. Thus, our data provide evidence that 5-aza-CdR is highly efficient against ALCL and warrants further clinical evaluation for future therapeutic use. PMID:22687603

Harnessing the immune system through programmed death-1 blockade in the management of Hodgkin lymphoma

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Oncale MB

2017-02-01

Full Text Available Melody B Oncale, Hossein Maymani, Loretta J Nastoupil Department of Lymphoma and Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: Immunotherapy is a rapidly evolving therapeutic option in the treatment of lymphoma. Neoplastic cells evade immune recognition through the programmed death (PD-1/PD-ligand immune checkpoint pathway. Several novel agents have been developed to restore the immune system’s ability to recognize and destroy cancer cells. Nivolumab and pembrolizumab are two anti-PD-1 antibodies that have demonstrated success in the treatment of refractory Hodgkin lymphoma. Harnessing the immune system’s ability to target neoplastic cells, ideally without the use of cytotoxic chemotherapeutic agents, is one way in which these novel agents are changing the therapeutic landscape in the treatment of lymphomas. Here, we review the emerging data regarding checkpoint inhibitors in the management of Hodgkin lymphoma, the unique adverse effects encountered with the use of these agents, and a practical approach to the management of these adverse effects. Additionally, we discuss upcoming trials that will further assess the promising future developments of checkpoint inhibition in the treatment of not only Hodgkin lymphoma but also other B cell lymphomas and myeloma. These agents offer immense promise of a future where many lymphomas can be treated without the toxic effects of chemotherapeutic agents. Keywords: Hodgkin lymphoma, programmed death-1, nivolumab, pembrolizumab, lymphoma

Immuno- and chemotherapy in the treatment of non-Hodgkins lymphomas

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Dwilewicz-Trojaczek, J.; Charlinski, G.

2009-01-01

Non-Hodgkin's lymphomas is a heterogeneous group of neoplasms. The lymphomas have various origins: from B and T cells. REAL/WHO classification system of NHL subdivided these diseases into lymphoma from precursor and peripheral lymphocytes. Clinical course may be: very aggressive and aggressive (generally - curable disease); and indolent lymphoma (generally - curable disease). The treatment of each subtype NHL is different, correct diagnosis is critically important. In the treatment of aggressive NHL are used combined chemotherapy, the addition of monoclonal antibody has greatly increased its efficacy. There are several therapeutic strategies to treat indolent NHL. The treatment of asymptomatic indolent lymphoma offers no benefit, and these patients may be observed. Once symptomatic, front-line therapy consist of single agent or combination chemotherapy, often combined with monoclonal antibody. The monoclonal antibodies have revolutionized the treatment of NHL. Monoclonal antibody fixes the antigen on the membrane o f the lymphoma cells. Monoclonal antibodies there are unconjugated, used alone or combined with chemotherapy (immunochemotherapy) or combined with immunotoxins or radionuclides (radioimmunotherapy). This is the progress in the treatment of lymphoma. (authors)

Lymphoma immunotherapy: vaccines, adoptive cell transfer and immunotransplant

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Brody, Joshua; Levy, Ronald

2017-01-01

Therapy for non-Hodgkin lymphoma has benefited greatly from basic science and clinical research such that chemotherapy and monoclonal antibody therapy have changed some lymphoma subtypes from uniformly lethal to curable, but the majority of lymphoma patients remain incurable. Novel therapies with less toxicity and more specific targeting of tumor cells are needed and immunotherapy is among the most promising of these. Recently completed randomized trials of idiotype vaccines and earlier-phase trials of other vaccine types have shown the ability to induce antitumor T cells and some clinical responses. More recently, trials of adoptive transfer of antitumor T cells have demonstrated techniques to increase the persistence and antitumor effect of these cells. Herein, we discuss lymphoma immunotherapy clinical trial results and what lessons can be taken to improve their effect, including the combination of vaccination and adoptive transfer in an approach we have dubbed ‘immunotransplant’. PMID:20636025

Primary lymphoma of appendix: Ultrasound finding

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Sotillos Parra, V.E.; Belda Serrano, J.; Mota Castilla, A.; Falomir Gil, G.; Abreu Maqueda, V.; Trigueris Sanchez, M.; Hernandez Barcelo, J.E.; Martinez Diaz, F.

1994-01-01

We present an uncommon case of primary lymphoma of the appendix in a patient who complained of discomfort in lower right quadrant. The findings revealed by ultrasound, barium enema and CT scan are reported and the diagnostic aspects of this appendiceal tumor and others are discussed. (Author) 6 refs

Identification of IgH gene rearrangement and immunophenotype in an animal model of Epstein-Barr virus-associated lymphomas.

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Zhang, Yang; Peng, Xueqin; Tang, Yunlian; Gan, Xiaoning; Wang, Chengkun; Xie, Lu; Xie, Xiaoli; Gan, Runliang; Wu, Yimou

2016-10-01

Epstein-Barr virus (EBV) is a human oncogenic herpesvirus associated with lymphoma and nasopharyngeal carcinoma. Because the susceptible hosts of EB virus are limited to human and cotton-top tamarins (Saguinus oedipus), there have been no appropriate animal models until the lymphoma model induced by EBV in human peripheral blood lymphocyte (hu-PBL)/SCID chimeric mice was reported. However, it is still controversial whether the EBV-associated lymphoma induced in hu-PBL/SCID mice is a monoclonal tumor. In this study, we transplanted normal human peripheral blood lymphocytes (hu-PBL) from six donors infected with EBV into SCID mice to construct hu-PBL/SCID chimeric mice. The induced tumors were found in the mediastinum or abdominal cavity of SCID mice. Microscopic observation exhibited tumor cells that were large and had a plasmablastic, centroblastic or immunoblastic-like appearance. Immunophenotyping assays showed the induced tumors were LCA-positive, CD20/CD79a-positive (markers of B cells), and CD3/CD45RO-negative (markers of T cells). A human-specific Alu sequence could be amplified by Alu-PCR. This confirmed that induced tumors were B-cell lymphomas originating from the transplanted human lymphocytes rather than mouse cells. EBER in situ hybridization detected positive signals in the nuclei of the tumor cells. Expression of EBV-encoded LMP1, EBNA-1, and EBNA-2 in the tumors was significantly positive. PCR-based capillary electrophoresis analysis of IgH gene rearrangement revealed a monoclonal peak and single amplification product in all six cases of induced tumors. This indicated that EBV can induce monoclonal proliferation of human B lymphocytes and promotes the development of lymphoma. J. Med. Virol. 88:1804-1813, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Impact of the scintigraphy of somatostatin receptors upon the therapeutic strategy in patients bearing digestive endocrine tumors

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Lebtahi, R.; Cadiot, G.; Genin, R.; Delahaye, N.; Faraggi, M.; Daou, D.; Peker, C.; Migon, M.; Le Guludec, D.

1997-01-01

The scintigraphy of somatostatin receptors (SSR) is a sensible method for detecting the gastroenteric-pancreatic endocrine tumors and their metastases. The aim of this study is to evaluate the clinical impact of the results of SSR in taking patients in therapeutic charge. A hundred and sixty patients bearing biologically and/or histologically proved digestive endocrine tumors were prospectively studied. The patients were classified in 3 groups: group I - 90 patients with no known metastases; group II - 59 patients with liver metastases and group III - 11 patients with known extra-hepatic metastases. The results of the scintigraphy were compared with those of conventional imaging. The following results were obtained: in group 1 (90 patients) the conventional imaging has allowed detecting 53 primitive tumors in 44 patients. The SSR visualized 68% of these sites and has detected 26 supplementary primitive sites in 20 patients and 29 metastatic sites in 25 patients. In group II the scintigraphy has detected 95% of hepatic metastases and revealed 23 new metastasis sites and 18/59 patients. In group III the scintigraphy has detected 11 new sites in 7 patients. The results of scintigraphy modified the patient's classification in 38 cases (24%). The therapeutic strategy was modified for 40 patients (25%). In conclusion, the scintigraphy of somatostatin receptors is able to detect a significant number of digestive endocrine tumors what has important implications for therapeutical planning of the treatment of patients. It must be carried out during pre-therapeutic extension examination of these tumors

Expression of CD56 and Epstein-Barr virus in nasal/nasopharyngeal lymphoma

International Nuclear Information System (INIS)

Lee, Seung Sook; Cho, Kyung Ja

1997-12-01

We examined malignant lymphomas and polymorphic reticulosis of nasal cavity, nasopharynx, and palate, diagnosed at Korea Cancer Center Hospital from 1987 to 1996. With immunophenotypic study, we reclassified nasal/nasopharyngeal lymphomas into three categories: CD56-positive T/NK lymphoma, CD56-negative lymphoma and B-cell lymphoma. Malignant lymphomas of nasal cavity, nasopharynx and palate were 95 patient, that comprised 11% of the total lymphoma cases, and it was the most common extranodal lymphoma. Twenty-five percent were B-cell lymphomas and 75 % were T/NK lymphomas. According to site, nasal cavity was the most frequent and 91 % of nasal cavity lymphomas were T/NK type. CD56-positive T/NK comprised 82 % of total T/NK lymphomas and CD56-negative cases were 18 %. In 89 % of total T/NK lymphomas, many tumor cells expressed EBER-1 in their nuclei (CD56+ T/NK lymphoma: 97 % of EBV expression, CD56-T-cell lymphoma; 60%). Only one case (5%) of B-cell lymphoma showed EBER-1 positivity in a few cells. CD56+ T/NK lymphomas showed significantly more angiocentricity and severe necrosis than CD56- cases. Although it has no statistical significance, T/NK lymphomas has a tendency to lower survival rates than B-cell lymphomas at 1 year and 2 year. CD56+ T/NK lymphomas has a tendency to lower survival than CD56- T/NK lymphomas (p > 0.05). Our results of this project will serve important basic materials in diagnosing and studying lymphoma. (author). 25 refs., 4 tabs., 4 figs

Protein 53 expression in a mixed Labrador subcutaneous lymphoma

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Annahita Rezaie

2012-06-01

Full Text Available An 11 year – old mixed female Labrador was presented with two masses in trunk and neck. The tumoral masses were excised and sent for histopathological and immunohistochemical analyses. Histopathological examination of masses revealed diffuse infiltration of small sized lymphoid cells in subcutaneous tissue which were intense around the blood vessels. More than 10% lymphoid cells were CD3 positive in the immunohistochemical staining and most of them were accumulated around vessels. Protein 53 (p53 expression was detected by brown nuclei in immunohistochemical staining. Subcutaneous lymphoma was diagnosed according to histopathological results. After 6 months the case was referred with multicentric lymphoma and based on the owner request euthanasia was performed. These findings emphasize on poor prognosis for tumors with p53 mutation.

High resolution genome-wide analysis of chromosomal alterations in Burkitt's lymphoma.

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Saloua Toujani

Full Text Available Additional chromosomal abnormalities are currently detected in Burkitt's lymphoma. They play major roles in the progression of BL and in prognosis. The genes involved remain elusive. A whole-genome oligonucleotide array CGH analysis correlated with karyotype and FISH was performed in a set of 27 Burkitt's lymphoma-derived cell lines and primary tumors. More than half of the 145 CNAs2 Mb, gains were found in 1q (12/27, 13q (7/27, 7q (6/27, 8q(4/27, 2p (3/27, 11q (2/27 and 15q (2/27. Losses were found in 3p (5/27, 4p (4/27, 4q (4/27, 9p (4/27, 13q (4/27, 6p (3/27, 17p (3/27, 6q (2/27,11pterp13 (2/27 and 14q12q21.3 (2/27. Twenty one minimal critical regions (MCR, (range 0.04-71.36 Mb, were delineated in tumors and cell lines. Three MCRs were localized to 1q. The proximal one was mapped to 1q21.1q25.2 with a 6.3 Mb amplicon (1q21.1q21.3 harboring BCA2 and PIAS3. In the other 2 MCRs, 1q32.1 and 1q44, MDM4 and AKT3 appeared as possible drivers of these gains respectively. The 13q31.3q32.1 MCR contained an amplicon and ABCC4 might be the driver of this amplicon. The 40 Kb 2p16.1 MCR was the smallest gained MCR and specifically encompassed the REL oncogene which is already implicated in B cell lymphomas. The most frequently deleted MCR was 3p14.1 that removed the fifth exon of FHIT. Further investigations which combined gene expression and functional studies are essential to understand the lymphomagenesis mechanism and for the development of more effective, targeted therapeutic strategies.

Pancoast syndrome: A rare presentation of non-Hodgkin′s lymphoma

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Anirban Sarkar

2013-01-01

Full Text Available Pancoast syndrome is a common presentation of bronchogenic carcinoma, but other malignancies are rarely cited as its cause. Pancoast syndrome due to non-Hodgkin′s lymphoma is rarely described in the literature. Here, we report a case of Pancoast syndrome due to non-Hodgkin′s lymphoma to increase the awareness of the clinicians regarding essentiality of tissue diagnosis of Pancoast tumor before starting the treatment.

Identification of genuine primary pulmonary NK cell lymphoma via clinicopathologic observation and clonality assay.

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Gong, Li; Wei, Long-Xiao; Huang, Gao-Sheng; Zhang, Wen-Dong; Wang, Lu; Zhu, Shao-Jun; Han, Xiu-Juan; Yao, Li; Lan, Miao; Li, Yan-Hong; Zhang, Wei

2013-08-19

Extranodal natural killer (NK)/T-cell lymphoma, nasal type, is an uncommon lymphoma associated with the Epstein-Barr virus (EBV). It most commonly involves the nasal cavity and upper respiratory tract. Primary pulmonary NK/T cell lymphoma is extremely rare. If a patient with a NK or T-cell tumor has an unusual reaction to treatment or an unusual prognosis, it is wise to differentiate NK from T-cell tumors. The clinicopathologic characteristics, immunophenotype, EBV in situ hybridization, and T cell receptor (TCR) gene rearrangement of primary pulmonary NK cell lymphoma from a 73-year-old Chinese woman were investigated and the clonal status was determined using female X-chromosomal inactivation mosaicism and polymorphisms at the phosphoglycerate kinase (PGK) gene. The lesion showed the typical histopathologic characteristics and immunohistochemical features of NK/T cell lymphoma. However, the sample was negative for TCR gene rearrangement. A clonality assay demonstrated that the lesion was monoclonal. It is concluded that this is the first recorded case of genuine primary pulmonary NK cell lymphoma. The purpose of the present work is to recommend that pathologists carefully investigate the whole lesion to reduce the likelihood that primary pulmonary NK cell lymphoma will be misdiagnosed as an infectious lesion. In addition, TCR gene rearrangement and clonal analysis, which is based on female X-chromosomal inactivation mosaicism and polymorphisms at PGK and androgen receptor (AR) loci, were found to play important roles in differentiating NK cell lymphoma from T cell lymphoma. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5205300349457729.

Comparison of squamous cell carcinoma with non-Hodgkin's lymphoma of tonsillar region

International Nuclear Information System (INIS)

Tsukiyama, Iwao; Yamashita, Kohsuke; Kajiura, Yuuichi; Ogino, Takashi; Akine, Yasuyuki; Egawa, Sunao; Ono, Isamu

1987-01-01

A total of 98 patients with malignant tumors of the tonsil (Squamous cell carcinoma, 34 patients, Non-Hodgkin's lymphoma, 64 patients) werw treated with radiation therapy between 1962 and 1979 at the National Cancer Center Hospital. All were staged by the TNM system, using UICC Classification 1978. With regard to stage distribution, Stage III is most frequent (47.1 %) in squamous cell carcinoma, Stage IV is most frequent (48.4 %) in Non-Hodgkin's lymphoma. Much more advanced cases were included in Non-Hodgkin's lymphoma. Five year survival rate for patients with squamous cell carcinoma and Non-Hodgkin's lymphoma were 49 % and 62 %, respectively. 50 % survival months with squamous cell carcinoma and Non-Hodgkin's lymphoma were 58.7 months and 195.5 months, respectively. Better prognosis was observed in Non-Hodgkin's lymphoma than squamous cell cacinoma. (author)

Primary intestinal hodgkin′s lymphoma: An uncommon presentation

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Shruti Sharma

2013-01-01

Full Text Available Primary intestinal lymphoma is a rare lymphoproliferative neoplasm of the small intestine. The primary nature is established on the basis of lack of evidence of lymphoma on chest X-ray, computerized tomographic scan, peripheral blood or bone marrow puncture. Tumor involvement is limited to the gastrointestinal tract, the criteria for inclusion are that the symptoms related to the small intestine are predominant or the only symptoms at the time of laparotomy. Hodgkin′s lymphoma (HL primarily in the small intestine is a rare entity and an uncommon presentation of the disease. Ileum is the more common site of infliction than the jejunum because of its abundant lymphoid follicles. Here, we present a case of primary intestinal HL, in a 30-year-old male.

Orbital MALT Lymphoma: A Case Report

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Shobha G Pai

2004-08-01

Full Text Available A case of orbital MALT (mucous associated lymphoid tissue lymphoma is reported for its rarity. It presented as a large tumor obscuring the whole eye with loss of vision, without any signs of dissemination and remained free of recurrence or metastasis 12 months after undergoing simple surgical excision.

A Mitochondrial Power Play in Lymphoma

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DeBerardinis, Ralph J.

2012-01-01

Deregulated energetics is a hallmark of malignancy, but metabolic heterogeneity among individual tumors is unknown. A study by Caro et al. in this issue of Cancer Cell demonstrates that a subset of lymphomas is defined by reliance on mitochondrial energy generation and is selectively killed when this pathway is impaired.

Results from radiant treatment in no Hodgkin's lymphomas of adults

International Nuclear Information System (INIS)

Alert, J.; Rodriguez, E.; Mesa, E.; Diaz, C.

1982-01-01

From 1973 to 1979, at the Institute of Oncology and Radiobiology, Havana City, 91 adults were irradiated because they underwent no Hodgkin's lymphomas at Stage I (located) and Stage II (regional extension) to whom radiant treatment was the basic therapeutic selection, with single or multiple fields and dose ranging between 3 500 and 4 000 rads-tumor, and some of them at Stage III, where primary treatment was chemotherapy. Present survival for all of them after 3 and 5 years is 55.7% and 54.7%, with 84.4% for patients at Stage I, 55.8% and 52.4% for Stage II and 33.8% for Stage III. Survival was similar for both sexes; in the same way ganglionar processes and those of extraganglionar localization presented no significant survival differences. Only to 7 patients (7.7%) modular forms were diagnosed. (author)

Primary non-Hodgkin's lymphoma of breast – A rare cause of breast lump

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Veena Gupta

2017-03-01

Full Text Available We, here, report a case of primary breast lymphoma in a 59 years old female. The diagnosis was suspected on fine needle aspiration cytology and confirmed on excision biopsy of the tumor. Histology and immunophenotyping were in accordance with non-Hodgkin's diffuse large B-cell lymphoma. The patient has been planned for adjuvant chemoradiation. The management and outcome of primary breast lymphoma and carcinoma are totally different. Early and prompt diagnosis of primary breast lymphoma is of utmost importance to avoid unnecessary mastectomies. Fine needle aspiration cytology supplemented by immuno-cytochemistry can be applied as a reliable and cost-effective tool in the early diagnosis of primary breast lymphomas, while histopathology and immunohistochemistry are conclusive.

Extra-nodal lymphoma. A survey of Japan lymphoma radiation therapy group

International Nuclear Information System (INIS)

Oguchi, Masahiko; Ikeda, Hiroshi; Nakamura, Shigeo

2002-01-01

The purpose of this study was to examine, retrospectively, national-wide clinical data of patients with localized extranodal non-Hodgkin's lymphoma (NHL) who were treated by radiation therapy with or without chemotherapy. The survey was carried out at 25 radiation oncology institutions in Japan in 1998. In 1999, according to the Revised European American Lymphoma (REAL) classification, central pathological review conducted at Aichi cancer center was carried out for the data from 7 radiation oncology institutions. The 5-year progression free survival rates (PFS) were calculated to identify prognostic factors. Survey: Data from 1, 141 patients with stage I and II NHL were recruited from 1988 through 1992. Of them, 787 patients, who were treated using definitive radiotherapy with or without chemotherapy for intermediate and high-grade lymphomas in Working Formulation, constituted the core of this study. Primary tumors arose mainly from extra-nodal organs (71%) in the head and neck (Waldeyer's ring: 41%, thyroid gland: 7%, nasal cavities: 5%, oral cavities: 4%, sinus: 3%, orbital structures: 3%, skin: 2% and etc.). The median age of 60 years for patients with extra-nodal NHL was higher than that of 56 years for patients with nodal NHL (p<0.01). Female were dominant in incidence of extra-nodal NHL arising from the thyroid gland, skin and gastrointestinal tract. The percentage of stage I to the extra-nodal NHL from orbit, sino-nasal presentation was higher than that of other NHLs. The percentage of stage II to the extra-nodal NHL from Waldeyer's ring and thyroid gland was higher than that of other NHLs. Central pathological review was carried out for pathological data from 79 patients (Waldeyer's ring: 45, thyroid gland: 19, sinonasal cavities: 15). Of these, diffuse large B cell lymphoma (DLBCL) composed 63% of all patients, mucosa associated lyumphoid tissue lymphoma (MALT-L): 16%, Natural Killer/T cell lymphoma (NK/T-L): 11%, and mantle cell lymphoma: 5% in REAL

Monte Carlo calculation of the maximum therapeutic gain of tumor antivascular alpha therapy

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Huang, Chen-Yu; Oborn, Bradley M.; Guatelli, Susanna; Allen, Barry J. [Centre for Experimental Radiation Oncology, St. George Clinical School, University of New South Wales, Kogarah, New South Wales 2217 (Australia); Illawarra Cancer Care Centre, Wollongong, New South Wales 2522, Australia and Centre for Medical Radiation Physics, University of Wollongong, New South Wales 2522 (Australia); Centre for Medical Radiation Physics, University of Wollongong, New South Wales 2522 (Australia); Centre for Experimental Radiation Oncology, St. George Clinical School, University of New South Wales, Kogarah, New South Wales 2217 (Australia)

2012-03-15

Purpose: Metastatic melanoma lesions experienced marked regression after systemic targeted alpha therapy in a phase 1 clinical trial. This unexpected response was ascribed to tumor antivascular alpha therapy (TAVAT), in which effective tumor regression is achieved by killing endothelial cells (ECs) in tumor capillaries and, thus, depriving cancer cells of nutrition and oxygen. The purpose of this paper is to quantitatively analyze the therapeutic efficacy and safety of TAVAT by building up the testing Monte Carlo microdosimetric models. Methods: Geant4 was adapted to simulate the spatial nonuniform distribution of the alpha emitter {sup 213}Bi. The intraluminal model was designed to simulate the background dose to normal tissue capillary ECs from the nontargeted activity in the blood. The perivascular model calculates the EC dose from the activity bound to the perivascular cancer cells. The key parameters are the probability of an alpha particle traversing an EC nucleus, the energy deposition, the lineal energy transfer, and the specific energy. These results were then applied to interpret the clinical trial. Cell survival rate and therapeutic gain were determined. Results: The specific energy for an alpha particle hitting an EC nucleus in the intraluminal and perivascular models is 0.35 and 0.37 Gy, respectively. As the average probability of traversal in these models is 2.7% and 1.1%, the mean specific energy per decay drops to 1.0 cGy and 0.4 cGy, which demonstrates that the source distribution has a significant impact on the dose. Using the melanoma clinical trial activity of 25 mCi, the dose to tumor EC nucleus is found to be 3.2 Gy and to a normal capillary EC nucleus to be 1.8 cGy. These data give a maximum therapeutic gain of about 180 and validate the TAVAT concept. Conclusions: TAVAT can deliver a cytotoxic dose to tumor capillaries without being toxic to normal tissue capillaries.

A phase II study of the oral JAK1/JAK2 inhibitor ruxolitinib in advanced relapsed/refractory Hodgkin lymphoma

NARCIS (Netherlands)

E. van den Neste (Eric); J.-L. André (Jean-Luc); Gastinne, T. (Thomas); A. Stamatoullas (Aspasia); C. Haioun (Corinne); Belhabri, A. (Amine); O. Reman (Oumédaly); O. Casasnovas (O.); H. Ghesquieres; G.E.G. Verhoef (Gregor); Claessen, M.-J. (Marie-José); H.A. Poirel (Hélène A); M.-C. Copin; Dubois, R. (Romain); P. Vandenberghe (Peter); Stoian, I.-A. (Ioanna-Andrea); Cottereau, A.S. (Anne S.); Bailly, S. (Sarah); L. Knoops (Laurent); F. Morschhauser (Frank)

2018-01-01

textabstractJAK2 constitutive activation/overexpression is common in classical Hodgkin lymphoma, and several cytokines stimulate Hodgkin lymphoma cells by recognizing JAK1-/JAK2-bound receptors. JAK blockade may thus be therapeutically beneficial in Hodgkin lymphoma. In this phase II study we

Primary immunodeficiencies and B-cell lymphomas.

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Martín-Mateos, María Anunciación; Piquer Gibert, Mónica

In primary immunodeficiencies there is a failure in the anti-tumor defense. Common variable immunodeficiency (CVID) is one of the most common primary immunodeficiencies characterized by an alteration in the differentiation of B lymphocytes (BL). Epstein-Barr virus (EBV) is an ubiquitous virus that selectively infects the BL. In patients with immunodeficiency, uncontrolled proliferation of infected BL and the action of viral proteins promote the development of lymphomas. At the University Hospital Sant Joan de Deu, Barcelona, 28 patients were diagnosed with CVID from 2000 to 2013. This paper describes four patients who developed non-Hodgkin's lymphoma (NHL). The lymphoma was associated with EBV in two of the cases. Patients were<18 years old, diagnosed with lymphoma between 4 and 13 years old. Two patients were treated with rituximab as monotherapy and achieved complete remission. Two patients were treated with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) and radiotherapy or rituximab and achieved complete remission. Early detection of EBV infections and NHL in all patients diagnosed with CVID is recommended, regardless of age at diagnosis. Copyright © 2016 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Primary Effusion Lymphoma without an Effusion: A Rare Case of Solid Extracavitary Variant of Primary Effusion Lymphoma in an HIV-Positive Patient

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Hamza Hashmi

2018-01-01

Full Text Available Primary effusion lymphoma (PEL is a unique form of non-Hodgkin lymphoma, usually seen in severely immunocompromised, HIV-positive patients. PEL is related to human herpesvirus-8 (HHV-8 infection, and it usually presents as a lymphomatous body cavity effusion in the absence of a solid tumor mass. There have been very few case reports of HIV-positive patients with HHV-8-positive solid tissue lymphomas not associated with an effusion (a solid variant of PEL. In the absence of effusion, establishing an accurate diagnosis can be challenging, and a careful review of morphology, immunophenotype, and presence of HHV-8 is necessary to differentiate from other subtypes of non-Hodgkin lymphoma. Treatment involves intensive chemotherapy, and prognosis is usually poor. We present a rare case of a PEL variant in an HIV-positive patient who presented with extensive lymphadenopathy without any associated effusions.

Tumor Therapeutics Work as Stress Inducers to Enhance Tumor Sensitivity to Natural Killer (NK) Cell Cytolysis by Up-regulating NKp30 Ligand B7-H6.

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Cao, Guoshuai; Wang, Jian; Zheng, Xiaodong; Wei, Haiming; Tian, Zhigang; Sun, Rui

2015-12-11

Immune cells are believed to participate in initiating anti-tumor effects during regular tumor therapy such as chemotherapy, radiation, hyperthermia, and cytokine injection. One of the mechanisms underlying this process is the expression of so-called stress-inducible immunostimulating ligands. Although the activating receptor NKG2D has been proven to play roles in tumor therapy through targeting its ligands, the role of NKp30, another key activating receptor, is seldom addressed. In this study, we found that the NKp30 ligand B7-H6 was widely expressed in tumor cells and closely correlated to their susceptibility to NK cell lysis. Further studies showed that treatment of tumor cells with almost all standard tumor therapeutics, including chemotherapy (cisplatin, 5-fluorouracil), radiation therapy, non-lethal heat shock, and cytokine therapy (TNF-α), could up-regulate the expression of B7-H6 in tumor cells and enhance tumor sensitivity to NK cell cytolysis. B7-H6 shRNA treatment effectively dampened sensitization of tumor cells to NK-mediated lysis. Our study not only reveals the possibility that tumor therapeutics work as stress inducers to enhance tumor sensitivity to NK cell cytolysis but also suggests that B7-H6 could be a potential target for tumor therapy in the future. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

[Primary presentation of non-hodgkin lymphoma. Report of a case].

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Mirpuri-Mirpuri, P G; Alvarez-Cordovés, M M; Pérez-Monje, A

2013-09-01

Lymphomas are the most common non-epithelial tumors of the head and neck and its incidence has increased in recent decades. Around 10% are extranodal lymphomas, and in more than half of the cases are located in Waldeyer's lymphatic ring. The most common presenting symptoms are odynophagia and dysphagia (68%), and symptoms suggestive of oropharyngeal cancer such as cough, hoarseness, earache, feeling of occupation in the back of the mouth, throat or neck. In non-Hodgkin lymphomas in this location, B symptoms (weight loss, fever and sweating) are rare (5%). The histological subtype of each individual lymphoma affects the evaluation, therapy and prognosis. Copyright © 2012 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

Plasma Cell-Free DNA in Paediatric Lymphomas

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Mussolin, Lara; Burnelli, Roberta; Pillon, Marta; Carraro, Elisa; Farruggia, Piero; Todesco, Alessandra; Mascarin, Maurizio; Rosolen, Angelo

2013-01-01

Background: Extracellular circulating DNA (cfDNA) can be found in small amounts in plasma of healthy individuals. Increased levels of cfDNA have been reported in patients with cancer of breast, cervix, colon, liver and it was shown that cfDNA can originate from both tumour and non-tumour cells. Objectives: Levels of cfDNA of a large series of children with lymphoma were evaluated and analyzed in relation with clinical characteristics. Methods: plasma cfDNA levels obtained at diagnosis in 201 paediatric lymphoma patients [43 Hodgkin lymphomas (HL), 45 anaplastic large cell lymphomas (ALCL), 88 Burkitt lymphomas (BL), 17 lymphoblastic (LBL), 8 diffuse large B cell lymphoma (DLBCL)] and 15 healthy individuals were determined using a quantitative PCR assay for POLR2 gene and, in addition, for NPM-ALK fusion gene in ALCL patients. Wilcoxon rank sum test was used to compare plasma levels among different patient subgroups and controls and to analyze relationship between levels of cfDNA and clinical characteristics. Results: Levels of cfDNA in lymphoma patients were significantly higher compared with controls (p<0.0001). CfDNA was associated with median age (p=0.01) in HL, and with stage in ALCL (p=0.01). In HL patients high cfDNA levels were correlated with poor prognosis (p=0.03). In ALCL we found that most of the cfDNA (77%) was non-tumor DNA. Conclusion: level of plasma cfDNA might constitute an important non-invasive tool at diagnosis in lymphoma patients' management; in particular in patients with HL, cfDNA seems to be a promising prognostic biomarker. PMID:23678368

Minimal Residual Disease Assessment in Lymphoma: Methods and Applications.

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Herrera, Alex F; Armand, Philippe

2017-12-01

Standard methods for disease response assessment in patients with lymphoma, including positron emission tomography and computed tomography scans, are imperfect. In other hematologic malignancies, particularly leukemias, the ability to detect minimal residual disease (MRD) is increasingly influencing treatment paradigms. However, in many subtypes of lymphoma, the application of MRD assessment techniques, like flow cytometry or polymerase chain reaction-based methods, has been challenging because of the absence of readily detected circulating disease or canonic chromosomal translocations. Newer MRD detection methods that use next-generation sequencing have yielded promising results in a number of lymphoma subtypes, fueling the hope that MRD detection may soon be applicable in clinical practice for most patients with lymphoma. MRD assessment can provide real-time information about tumor burden and response to therapy, noninvasive genomic profiling, and monitoring of clonal dynamics, allowing for many possible applications that could significantly affect the care of patients with lymphoma. Further validation of MRD assessment methods, including the incorporation of MRD assessment into clinical trials in patients with lymphoma, will be critical to determine how best to deploy MRD testing in routine practice and whether MRD assessment can ultimately bring us closer to the goal of personalized lymphoma care. In this review article, we describe the methods available for detecting MRD in patients with lymphoma and their relative advantages and disadvantages. We discuss preliminary results supporting the potential applications for MRD testing in the care of patients with lymphoma and strategies for including MRD assessment in lymphoma clinical trials.

Genetic Recombination Between Stromal and Cancer Cells Results in Highly Malignant Cells Identified by Color-Coded Imaging in a Mouse Lymphoma Model.

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Nakamura, Miki; Suetsugu, Atsushi; Hasegawa, Kousuke; Matsumoto, Takuro; Aoki, Hitomi; Kunisada, Takahiro; Shimizu, Masahito; Saji, Shigetoyo; Moriwaki, Hisataka; Hoffman, Robert M

2017-12-01

The tumor microenvironment (TME) promotes tumor growth and metastasis. We previously established the color-coded EL4 lymphoma TME model with red fluorescent protein (RFP) expressing EL4 implanted in transgenic C57BL/6 green fluorescent protein (GFP) mice. Color-coded imaging of the lymphoma TME suggested an important role of stromal cells in lymphoma progression and metastasis. In the present study, we used color-coded imaging of RFP-lymphoma cells and GFP stromal cells to identify yellow-fluorescent genetically recombinant cells appearing only during metastasis. The EL4-RFP lymphoma cells were injected subcutaneously in C57BL/6-GFP transgenic mice and formed subcutaneous tumors 14 days after cell transplantation. The subcutaneous tumors were harvested and transplanted to the abdominal cavity of nude mice. Metastases to the liver, perigastric lymph node, ascites, bone marrow, and primary tumor were imaged. In addition to EL4-RFP cells and GFP-host cells, genetically recombinant yellow-fluorescent cells, were observed only in the ascites and bone marrow. These results indicate genetic exchange between the stromal and cancer cells. Possible mechanisms of genetic exchange are discussed as well as its ramifications for metastasis. J. Cell. Biochem. 118: 4216-4221, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Forced LIGHT expression in prostate tumors overcomes Treg mediated immunosuppression and synergizes with a prostate tumor therapeutic vaccine by recruiting effector T lymphocytes.

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Yan, Lisa; Da Silva, Diane M; Verma, Bhavna; Gray, Andrew; Brand, Heike E; Skeate, Joseph G; Porras, Tania B; Kanodia, Shreya; Kast, W Martin

2015-02-15

LIGHT, a ligand for lymphotoxin-β receptor (LTβR) and herpes virus entry mediator, is predominantly expressed on activated immune cells and LTβR signaling leads to the recruitment of lymphocytes. The interaction between LIGHT and LTβR has been previously shown to activate immune cells and result in tumor regression in a virally-induced tumor model, but the role of LIGHT in tumor immunosuppression or in a prostate cancer setting, where self antigens exist, has not been explored. We hypothesized that forced expression of LIGHT in prostate tumors would shift the pattern of immune cell infiltration toward an anti-tumoral milieu, would inhibit T regulatory cells (Tregs) and would induce prostate cancer tumor associated antigen (TAA) specific T cells that would eradicate tumors. Real Time PCR was used to evaluate expression of forced LIGHT and other immunoregulatory genes in prostate tumors samples. For in vivo studies, adenovirus encoding murine LIGHT was injected intratumorally into TRAMP-C2 prostate cancer cell tumor bearing mice. Chemokine and cytokine concentrations were determined by multiplex ELISA. Flow cytometry was used to phenotype tumor infiltrating lymphocytes and expression of LIGHT on the tumor cell surface. Tumor-specific lymphocytes were quantified via ELISpot assay. Treg induction and Treg suppression assays determined Treg functionality after LIGHT treatment. LIGHT in combination with a therapeutic vaccine, PSCA TriVax, reduced tumor burden. LIGHT expression peaked within 48 hr of infection, recruited effector T cells that recognized mouse prostate stem cell antigen (PSCA) into the tumor microenvironment, and inhibited infiltration of Tregs. Tregs isolated from tumor draining lymph nodes had impaired suppressive capability after LIGHT treatment. Forced LIGHT treatment combined with PSCA TriVax therapeutic vaccination delays prostate cancer progression in mice by recruiting effector T lymphocytes to the tumor and inhibiting Treg mediated

MYC/BCL2/BCL6 triple hit lymphoma: a study of 40 patients with a comparison to MYC/BCL2 and MYC/BCL6 double hit lymphomas.

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Huang, Wenting; Medeiros, L Jeffrey; Lin, Pei; Wang, Wei; Tang, Guilin; Khoury, Joseph; Konoplev, Sergej; Yin, C Cameron; Xu, Jie; Oki, Yasuhiro; Li, Shaoying

2018-05-21

High-grade B-cell lymphomas with MYC, BCL2, and BCL6 rearrangements (triple hit lymphoma) are uncommon. We studied the clinicopathologic features of 40 patients with triple hit lymphoma and compared them to 157 patients with MYC/BCL2 double hit lymphoma and 13 patients with MYC/BCL6 double hit lymphoma. The triple hit lymphoma group included 25 men and 15 women with a median age of 61 years (range, 34-85). Nine patients had a history of B-cell lymphoma. Histologically, 23 (58%) cases were diffuse large B-cell lymphoma and 17 cases had features of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma. Most cases of triple hit lymphoma were positive for CD10 (100%), BCL2 (95%), BCL6 (82%), MYC (74%), and 71% with MYC and BCL2 coexpression. P53 was overexpressed in 29% of triple hit lymphoma cases. The clinicopathological features of triple hit lymphoma patients were similar to patients with MYC/BCL2 and MYC/BCL6 double hit lymphoma, except that triple hit lymphoma cases were more often CD10 positive compared with MYC/BCL6 double hit lymphoma (p hit lymphoma and double hit lymphoma and overall survival in triple hit lymphoma patients was 17.6 months, similar to the overall survival of patients with double hit lymphoma (p = 0.67). Patients with triple hit lymphoma showing P53 overexpression had significantly worse overall survival compared with those without P53 overexpression (p = 0.04). On the other hand, double expressor status and prior history of B-cell lymphoma did not correlate with overall survival. In conclusion, most patients with triple hit lymphoma have an aggressive clinical course and poor prognosis and these tumors have a germinal center B-cell immunophenotype, similar to patients with double hit lymphomas. P53 expression is a poor prognostic factor in patients with triple hit lymphoma.

Nuclear medicine and lymphoma: the role of the FDG PET in non Hodgkin's lymphoma in children

International Nuclear Information System (INIS)

Montravers, F.; Kerrou, K.; Gutman, F.; Grahek, D.; Talbot, J.N.

2006-01-01

As for adult population, FDG PET is recognized as an efficient tool for staging, adaptation of therapy and follow-up of Hodgkin's disease in children. The interpretation of PET needs however to take into account some specificities of imaging as the frequent brown fat activation and the physiologic thymic uptake. The role of FDG PET in non Hodgkin's lymphoma (NHL) in children is less established. Although LNH are more frequent than Hodgkin 's lymphoma in children, FDG PET is rarely performed at diagnosis, probably due to the therapeutic emergency of these aggressive pediatric forms. During follow-up, FDG PET has been however shown to be useful, especially for the characterization of residual masses. (authors)

HELICOBACTER PYLORI AND t(11;18(q21;q21 TRANSLOCATION IN GASTRIC MALT LYMPHOMA

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Karine Sampaio LIMA

2014-04-01

Full Text Available Context Gastric mucosa-associated lymphoid tissue (MALT lymphoma is clearly associated with Helicobacter pylori gastritis and can be cured with anti- H pylori therapy alone. The presence of t(11;18(q21;q21 translocation is thought to predict a lower response rate to anti- H pylori treatment. Objectives To study the presence of t(11;18(q21;q21 genetic translocation and its clinical impact in low-grade gastric MALT lymphoma Brazilian patients. Methods A consecutive series of eight patients with gastric MALT lymphoma were submitted to gastroscopy, endoscopic ultrasound, histopathological examination, H pylori search and RT-PCR-based methodology. All patients received anti-H pylori treatment. Eradicated patients were followed-up every 3-6 months for 2 years. Results Eight patients were studied. All patients had tumor involvement restricted to the mucosa or submucosa and seven patients had low-grade gastric MALT lymphoma. All infected patients achieved H pylori eradication. Histological tumor regression was observed in 5/7 (71% of the low-grade gastric MALT lymphoma patients. The presence of t(11;18(q21;q21 translocation was found in 4 (57% of these patients; among them only two had histological tumor regression following H pylori eradication. Conclusions RT-PCR is a feasible and efficient method to detect t(11;18(q21;q21 translocation, being carried out in routine molecular biology laboratories. The early detection of such translocation can be very helpful for better targeting the therapy to be applied to gastric MALT lymphoma patients.

Activation of TAK1 by MYD88 L265P drives malignant B-cell Growth in non-Hodgkin lymphoma

International Nuclear Information System (INIS)

Ansell, S M; Hodge, L S; Secreto, F J; Manske, M; Braggio, E; Price-Troska, T; Ziesmer, S; Li, Y; Johnson, S H; Hart, S N; Kocher, J-P A; Vasmatzis, G; Chanan-Kahn, A; Gertz, M; Fonseca, R; Dogan, A; Cerhan, J R; Novak, A J

2014-01-01

Massively parallel sequencing analyses have revealed a common mutation within the MYD88 gene (MYD88 L265P ) occurring at high frequencies in many non-Hodgkin lymphomas (NHLs) including the rare lymphoplasmacytic lymphoma, Waldenström's macroglobulinemia (WM). Using whole-exome sequencing, Sanger sequencing and allele-specific PCR, we validate the initial studies and detect the MYD88 L265P mutation in the tumor genome of 97% of WM patients analyzed (n=39). Due to the high frequency of MYD88 mutation in WM and other NHL, and its known effects on malignant B-cell survival, therapeutic targeting of MYD88 signaling pathways may be clinically useful. However, we are lacking a thorough characterization of the role of intermediary signaling proteins on the biology of MYD88 L265P -expressing B cells. We report here that MYD88 L265P signaling is constitutively active in both WM and diffuse large B-cell lymphoma cells leading to heightened MYD88 L265P , IRAK and TRAF6 oligomerization and NF-κB activation. Furthermore, we have identified the signaling protein, TAK1, to be an essential mediator of MYD88 L265P -driven signaling, cellular proliferation and cytokine secretion in malignant B cells. Our studies highlight the biological significance of MYD88 L265P in NHL and reveal TAK1 inhibition to be a potential therapeutic strategy for the treatment of WM and other diseases characterized by MYD88 L265P

Clinical Utility of Circulating Tumor Cells in ALK-Positive Non-Small-Cell Lung Cancer.

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Faugeroux, Vincent; Pailler, Emma; Auger, Nathalie; Taylor, Melissa; Farace, Françoise

2014-01-01

The advent of rationally targeted therapies such as small-molecule tyrosine kinase inhibitors (TKIs) has considerably transformed the therapeutic management of a subset of patients with non-small-cell lung cancer (NSCLC) harboring defined molecular abnormalities. When such genetic molecular alterations are detected the use of specific TKI has demonstrated better results (overall response rate, progression free survival) compared to systemic therapy. However, the detection of such molecular abnormalities is complicated by the difficulty in obtaining sufficient tumor material, in terms of quantity and quality, from a biopsy. Here, we described how circulating tumor cells (CTCs) can have a clinical utility in anaplastic lymphoma kinase (ALK) positive NSCLC patients to diagnose ALK-EML4 gene rearrangement and to guide therapeutic management of these patients. The ability to detect genetic abnormalities such ALK rearrangement in CTCs shows that these cells could offer new perspectives both for the diagnosis and the monitoring of ALK-positive patients eligible for treatment with ALK inhibitors.

Protein glycosylation in cancers and its potential therapeutic applications in neuroblastoma

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Wan-Ling Ho

2016-09-01

Full Text Available Abstract Glycosylation is the most complex post-translational modification of proteins. Altered glycans on the tumor- and host-cell surface and in the tumor microenvironment have been identified to mediate critical events in cancer pathogenesis and progression. Tumor-associated glycan changes comprise increased branching of N-glycans, higher density of O-glycans, generation of truncated versions of normal counterparts, and generation of unusual forms of terminal structures arising from sialylation and fucosylation. The functional role of tumor-associated glycans (Tn, sTn, T, and sLea/x is dependent on the interaction with lectins. Lectins are expressed on the surface of immune cells and endothelial cells or exist as extracellular matrix proteins and soluble adhesion molecules. Expression of tumor-associated glycans is involved in the dysregulation of glycogenes, which mainly comprise glycosyltransferases and glycosidases. Furthermore, genetic and epigenetic mechanisms on many glycogenes are associated with malignant transformation. With better understanding of all aspects of cancer-cell glycomics, many tumor-associated glycans have been utilized for diagnostic, prognostic, and therapeutic purposes. Glycan-based therapeutics has been applied to cancers from breast, lung, gastrointestinal system, melanomas, and lymphomas but rarely to neuroblastomas (NBs. The success of anti-disialoganglioside (GD2, a glycolipid antigen antibodies sheds light on glycan-based therapies for NB and also suggests the possibility of protein glycosylation-based therapies for NB. This review summarizes our understanding of cancer glycobiology with a focus of how protein glycosylation and associated glycosyltransferases affect cellular behaviors and treatment outcome of various cancers, especially NB. Finally, we highlight potential applications of glycosylation in drug and cancer vaccine development for NB.

Allele-specific deletions in mouse tumors identify Fbxw7 as germline modifier of tumor susceptibility.

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Jesus Perez-Losada

Full Text Available Genome-wide association studies (GWAS have been successful in finding associations between specific genetic variants and cancer susceptibility in human populations. These studies have identified a range of highly statistically significant associations between single nucleotide polymorphisms (SNPs and susceptibility to development of a range of human tumors. However, the effect of each SNP in isolation is very small, and all of the SNPs combined only account for a relatively minor proportion of the total genetic risk (5-10%. There is therefore a major requirement for alternative routes to the discovery of genetic risk factors for cancer. We have previously shown using mouse models that chromosomal regions harboring susceptibility genes identified by linkage analysis frequently exhibit allele-specific genetic alterations in tumors. We demonstrate here that the Fbxw7 gene, a commonly mutated gene in a wide range of mouse and human cancers, shows allele-specific deletions in mouse lymphomas and skin tumors. Lymphomas from three different F1 hybrids show 100% allele-specificity in the patterns of allelic loss. Parental alleles from 129/Sv or Spretus/Gla mice are lost in tumors from F1 hybrids with C57BL/6 animals, due to the presence of a specific non-synonymous coding sequence polymorphism at the N-terminal portion of the gene. A specific genetic test of association between this SNP and lymphoma susceptibility in interspecific backcross mice showed a significant linkage (p = 0.001, but only in animals with a functional p53 gene. These data therefore identify Fbxw7 as a p53-dependent tumor susceptibility gene. Increased p53-dependent tumor susceptibility and allele-specific losses were also seen in a mouse skin model of skin tumor development. We propose that analysis of preferential allelic imbalances in tumors may provide an efficient means of uncovering genetic variants that affect mouse and human tumor susceptibility.

Histone deacetylase 1, 2, 6 and acetylated histone H4 in B- and T-cell lymphomas

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Marquard, L.; Poulsen, C.B.; Gjerdrum, L.M.

2009-01-01

AIMS: Histone deacetylase (HDAC) inhibitors are novel therapeutics in the treatment of peripheral T-cell lymphoma, unspecified (PTCL) and diffuse large B-cell lymphoma (DLBCL), where, for unknown reasons, T-cell malignancies appear to be more sensitive than B-cell malignancies. The aim was to det......AIMS: Histone deacetylase (HDAC) inhibitors are novel therapeutics in the treatment of peripheral T-cell lymphoma, unspecified (PTCL) and diffuse large B-cell lymphoma (DLBCL), where, for unknown reasons, T-cell malignancies appear to be more sensitive than B-cell malignancies. The aim...... was to determine HDAC expression in DLBCL and PTCL which has not previously been investigated. METHODS AND RESULTS: The expression of HDAC1, HDAC2, HDAC6 and acetylated histone H4 was examined immunohistochemically in 31 DLBCL and 45 PTCL. All four markers showed high expression in both DLBCL and PTCL compared...

Immunotherapy with rituximab in follicular lymphomas.

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Saguna, Carmen; Mut, Ileana Delia; Lupu, Anca Roxana; Tevet, Mihaela; Bumbea, Horia; Dragan, Cornel

2011-04-01

Non-Hodgkin Lymphomas (NHL) represent a recent and fascinating domain of hemato-oncology, in which remarkable progress has been made. The conventional treatments of indolent lymphomas do not extend the survival rate, nor do they cure. Recent directions are centered on using several new drugs that are capable of overcoming the mechanisms that are resistant to recovery. The initiation of immunotherapy (Rituximab in 1997) seems to have changed the natural evolution of follicular lymphomas (FL). It is possible that resistance to healing in follicular lymphomas may be neutralized with Rituximab by suppressing STAT-1 positive macrophages that are present in the cellular microenvironment.Thereinafter, the re-evaluation of recent models of prognostic and therapeutic paradigmas that were used in FL became compulsory.The purpose of the paper is to compare the evolution of patients with follicular lymphoma and the period of response, according to the treatments. The study group consisted of the 71 patients diagnosed with follicular lymphoma, out of a total of 767 malignant lymphatic proliferations with B cells, for a period of 7 years (2002-2008), at the Hematology Department, Hospital Coltea, Bucharest and Hematology Department, Universitary Hospital, BucharestResults and conclusions: Combining chemotherapy with Rituximab had better results compared to the same chemotherapy, administered alone, both in induction and in case of relapse. The overall response rate in our study group was 74.7%, out of which 42.3% complete remissions. The overall response rate was 84.61% in the Rituximab group, compared to 68.88% in patients without Rituximab.

PET/CT and beta-2-microglobulin in staging and therapeutic control after hematopoietic stem cell transplantation

International Nuclear Information System (INIS)

Vassileva, D.; Garcheva, M.; Kostadinova, I.

2013-01-01

Full text: Introduction: The transplantation of hematopoietic stem cells is used in lymphomas refractory to standard treatment. An exact re-staging is critical and the use of hybrid imaging methods has increased. The determined serum levels of beta-2 - microglobulin levels are also related to the progress of the disease and may be involved in determining the therapeutic effect. Materials and Methods: PET / CT studies were performed before and after transplantation of hematopoietic stem cells in patients with Hodgkin's disease and non-Hodgkin's lymphomas according to a the standard protocol, 60 minutes after injection of 18F-FDG using the apparatus Discovery 600. At the same time, the serum levels of beta-2 - microglobulin were determined. Results: Prior to transplantation nodal and extra nodal tumor infiltrates were visualized in the lungs and bones. In some of the patients a residual tumor was observed after the stem cell transplantation, which shows a partial response to the therapy. The serum levels of beta-2 - microglobulin were increased in the active phase of the disease and were normalized at remission. In the patients with partial response the values of the beta -2- microglobulin remain elevated. Conclusion: The use of PET / CT allows an accurate staging in patients with refractory lymphomas directed for transplantation and allows to register the effect of the therapy. The scintigraphic data show a good correlation with the beta-2 – microglobulin values in the serum

A diffuse mixed histiocytic-lymphocytic lymphoma associated with immunological abnormalities.

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Syrjänen, K J

1979-01-01

A diffuse generalized lymphoma histologically classified as mixed histiocytic-lymphocytic type and associated with profound immunologie abnormalities is reported. The patient had an autoimmune hemolytic anemia, an autoimmune thrombocytopenia, polyclonally increased IgG and IgM, polyclonal secretion of kappa and lamda chains into urine, very low serum complement C3 and antibodies against glomerulus and smooth muscle. When studied with the modern surface-marker techniques, the lesion was found to be composed of entirely lymphoid cells of the B-lymphocyte series. The proper classification of this tumor could be a primitive immunoblastic sarcoma. The relationship of the present tumor to the non-neoplastic angioimmunoblastic lymphadenopathia is discussed. The necessity of applying the surface-marker techniques in the classification of malignant lymphomas is emphasized.

Diagnosis of thyroid lymphoma and follow-up evaluation using Ga-67 scintigraphy

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Nishiyama, Yoshihiro; Yamamoto, Yuka; Yokoe, Koiku; Satoh, Katashi; Ohkawa, Motoomi

2003-01-01

A strong association between malignant lymphoma and Hashimoto's thyroiditis has frequently been reported. However, it is difficult to detect the lymphomatous transformation of Hashimoto's thyroiditis in the early stage. The purpose of the present study was to examine the usefulness of 67 Ga scintigraphy in the diagnosis and evaluation of the therapeutic effects during follow-up, in patients with a suspected diagnosis of primary thyroid lymphoma. Twenty-five patients who were suspected of having primary thyroid lymphoma and had undergone 67 Ga scintigraphy were studied. 67 Ga planar scintigraphy was performed 72 hours after injection of 67 Ga-citrate. The degree and pattern of 67 Ga accumulation were graded visually. Histopathology on biopsy examination revealed thyroid lymphoma in 17 and Hashimoto's thyroiditis in 8 patients. Abnormal accumulation of 67 Ga in the thyroid was seen in all of the 17 thyroid lymphoma cases with additional mediastinal and abdominal involvement in one. Fifteen of 17 thyroid lymphoma patients also underwent 67 Ga scintigraphy 2-4 weeks after chemotherapy and/or radiotherapy. All 15 patients showed diminishing 67 Ga accumulation and a good clinical course. In one patient with local recurrence, abnormal accumulation could be depicted by follow-up scintigraphy. However, diffuse or enlarged accumulation in the thyroid was seen in all of the 8 Hashimoto's thyroiditis cases. The degree of abnormal accumulation in the thyroid in clinically active phase thyroiditis was more intense than that in the chronic phase thyroiditis. 67 Ga scintigraphy was helpful to confirm the diagnosis of thyroid lymphoma and to evaluate the therapeutic effects during follow-up. However, 67 Ga scintigraphy may not always distinguish thyroid lymphoma from Hashimoto's thyroiditis, especially the active phase of the disease. (author)

Primary EBV-positive Hodgkin's lymphoma of the CNS under azathioprine treatment. Case report and review of the literature

International Nuclear Information System (INIS)

Henkenberens, Christoph; Christiansen, Hans; Franzke, Anke; Raab, Peter; Oschlies, Ilske; Klapper, Wolfram

2014-01-01

Retrospective and prospective cohort studies suggest that central nervous system involvement occurs in approximately 0.5 % of patients with advanced Hodgkin's lymphoma. The isolated primary intracranial manifestation of Hodgkin's lymphoma is an extremely rare finding, with few cases reported in the literature. Little is known about the optimal treatment and prognosis of these tumors. Here, we present a case report with a review of the literature. A 47-year-old Caucasian man with persistent frontal headache and unspecific vertigo for half a month was diagnosed with nodular space-occupying lesions in the cerebellum. His medical history included multiple sclerosis, which was treated for 20 years with the immunosuppressive drug azathioprine. Further staging revealed no additional lesions suspected of being malignant. The patient underwent total tumor resection. Immunohistopathological examination showed Epstein-Barr virus-associated classic Hodgkin's lymphoma. Diagnostic bone marrow punction excluded lymphoma involvement of the bone marrow. The patient had no B symptoms. Consequently, the patient was classified as having stage I E A disease according to the Modified Ann Arbor Classification of Hodgkin Lymphoma and received systemic chemotherapy followed by radiation therapy for the former cerebellar tumor region. He was in complete clinical remission at the last follow-up 9 months after the initial diagnosis. This case report and literature review suggest that multimodal treatment leads to a remarkable clinical outcome in Hodgkin's lymphoma with intracranial involvement. (orig.) [de

Ocular complication with therapeutic irradiation of malignant tumor in the maxilla

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Takahashi, Hisashi; Konno, Akiyoshi

1983-01-01

This paper describes the ocular complications of 33 cases who had undergone therapeutic irradiation for malignant tumor in the maxilla. Irradiation was performed with megavoltage x-ray of 6000 rads or more. Among the 18 patients with intraorbital infiltration of the tumor, 8 showed severe ocular lesion. In contrast, only 3 among the 15 patients without intraorbital infiltration showed severe lesions. Retinopathy was observed in 13 patients. Funduscopic findings and fluorescein angiograms were similar to those in diabetic retinopathy. One case of retinopathy with neovascular change was treated with panretinal argon laser photocoagulation; however, it was not successful. Most of the 7 glaucoma patients had neovascular glaucoma. They had the worst prognosis. (author)

MRI findings in primary brain lymphoma in immunocompetent patients

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Saeed Nadhim Younis

2017-08-01

Full Text Available Background and objective: Primary brain lymphoma is an extranodal aggressive intracranial neoplasm of lymphocytic origin originating and confined to the brain parenchyma and meninges. It is rare in immune competent patients, but its incidence is increasing. This retrospective study was conducted to record the MRI features of primary brain lymphoma at the time of diagnosis in immunocompetent patients. Methods: Of the 450 patients diagnosed with the brain tumor during a period of five years from 2008 to 2013, the clinical features and MRI findings of 16 cases of pathologically proven to be non-Hodgkin’s lymphoma were studied. All the patients were tested negative for HIV and there was no history of immune suppression drugs or any other chronic illness. All the patients were examined with MRI observing the tumor location, multifocality, signal intensity in different sequences, enhancement patterns, peritumoral edema, the presence of hemorrhage and calcification. Results: Of the 16 patients, including the monofocal and multifocal cases, 30 lesions exhibited. The mean age at diagnosis was 53 years. Nine patients (56.25% found to have a multifocal disease. In more than 75% of lesions, MRI was hypo to iso signal on T1 and T2. Mild to moderate perilesional edema, strong contrast enhancement and restricted diffusion were seen in all cases. The hemorrhagic tumor was noticed in four lesions (13.3%. No calcification and no leptomeningeal lesions were noted. The MRI images in post steroid therapy were studied within one month of treatment. Tumour regression was noticed in 21/30 (70%, stable in 3/30 (10% and progressing in 6/30 (20%. Conclusion: MRI is a reliable imaging technique in the management of patients with primary brain lymphoma. Early accurate diagnosis is crucial to avoid the unnecessary operation and shift patients from extensive surgery to chemoradiotherapy.

Central nervous system involvement of leukemia and systemic lymphoma in children. CT and MR findings

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Tomura, Noriaki; Hirano, Hiroko; Kato, Kohki; Sashi, Ryuji; Hashimoto, Manabu; Watarai, Jiro; Watanabe, Arata

1997-01-01

The purpose of this paper is to retrospectively evaluate CT and MR findings of central nervous system (CNS) involvement of leukemia and systemic lymphoma in children. Over a 12-year period, sixty-five patients with leukemia and fifteen patients with systemic lymphoma underwent cerebral CT and/or MR imaging. Nine patients were diagnosed as CNS involvement of leukemia and lymphoma. The CT and MR abnormalities in these patients were correlated with the findings of histology, cerebrospinal fluid cytology, and/or treatment. The age of the patients ranged from 0 to 15 years old. They consisted of 6 boys and 3 girls. The CT examinations were performed before and after contrast administration. MR examinations were performed on a 1.5-T unit, and T1-weighted, T2-weighted, and proton density-weighted images were obtained using spin-echo or fast spin-echo sequences. Tumor masses were present in seven with leukemia, and in two with malignant lymphoma. On the CT scan, tumor masses were hyperdense with contrast enhancement. On the MR images, their signals were variable. In all of nine patients, tumor masses were contiguous with a meningeal surface. Postcontrast T1-weighted images were valuable in demonstrating meningeal infiltration. Tumoral hemorrhage was found in two patients. In a patient with tumor at the superior sagittal sinus, venous infarct was observed. CNS leukemic and lymphomatous masses are almost hyperdense on the CT and they are characteristically contiguous with a meningeal surface. MR imaging was valuable in demonstrating meningeal infiltration. (K.H.)

PD-1 Blockade Can Restore Functions of T-Cells in Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma In Vitro.

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Lina Quan

Full Text Available Epstein-Barr virus-positive diffuse large B-cell lymphoma (EBV+DLBCL is an aggressive malignancy that is largely resistant to current therapeutic regimens, and is an attractive target for immune-based therapies. Anti-programmed death-1 (PD-1 antibodies showed encouraging anti-tumor effects in both preclinical models and advanced solid and hematological malignancies, but its efficacy against EBV+DLBCL is unknown. Herein, we performed experiments using co-culture system with T cells and lymphoma cell lines including EBV+DLBCL and EBV-DLBCL [including germinal center B-cell like (GCB-DLBCL and non-GCB-DLBCL] in vitro. We show that lymphoma cells augmented the expression of PD-1 on T cells, decreased the proliferation of T cells, and altered the secretion of multiple cytokines. However, through PD-1 blockade, these functions could be largely restored. Notbaly, the effect of PD-1 blockade on antitumor immunity was more effective in EBV+DLBCL than that in EBV-DLBCL in vitro. These results suggest that T-cell exhaustion and immune escape in microenvironment is one of the mechanisms underlying DLBCL; and PD-1 blockade could present as a efficacious immunotherapeutic treatment for EBV+DLBCL.

Distinct subtype distribution and somatic mutation spectrum of lymphomas in East Asia.

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Ren, Weicheng; Li, Wei; Ye, Xiaofei; Liu, Hui; Pan-Hammarström, Qiang

2017-07-01

Here, we give an updated overview of the subtype distribution of lymphomas in East Asia and also present the genome sequencing data on two major subtypes of these tumors. The distribution of lymphoma types/subtypes among East Asian countries is very similar, with a lower proportion of B-cell malignancies and a higher proportion of T/natural killer (NK)-cell lymphomas as compared to Western populations. Extranodal NK/T-cell lymphoma is more frequently observed in East Asia, whereas follicular lymphoma and chronic lymphocytic leukemia, are proportionally lower. The incidence rate of lymphoma subtypes in Asians living in the US was generally intermediate to the general rate in US and Asia, suggesting that both genetic and environmental factors may underlie the geographical variations observed.Key cancer driver mutations have been identified in Asian patients with diffuse large B-cell lymphoma or extranodal NK/T-cell lymphoma through genome sequencing. A distinct somatic mutation profile has also been observed in Chinese diffuse large B-cell lymphoma patients. The incidence and distribution of lymphoma subtypes differed significantly between patients from East Asia and Western countries, suggesting subtype-specific etiologic mechanisms. Further studies on the mechanism underlying these geographical variations may give new insights into our understanding of lymphomagenesis.

NON-HODGKIN'S LYMPHOMAS OF FEMALE REPRODUCTIVE SYSTEM

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A. V. Babkina

2008-01-01

Full Text Available Non-Hodgkin's lymphomas are extremely rare among all tumors of female reproductive system. Diagnostic mistakes and inadequate therapeu- tic tactics in these diseases are results of usual absence of alertness of gynecologists. The aims are to analyze reasons of diagnostic mistakes in patients with non-Hodgkin's lymphomas of female reproductive system and to discover definitive clinical and morphological characteristics of female reproductive system lymphoid tumors. During the period between 1989 and 2006, 305 cases of primary extranodal non-Hodgkin's lym- phomas were detected; female reproductive system was affected in 7% of patients (totally 40 patients, which were included in investigated group. In the whole analyzed group of women (n=40, median age 43 yrs, range 17-84 yrs, patients with primary lesion of female reproductive system had median age of 40 yrs and with secondary involvement - 46 yrs. Most of patients were fertile (60%, n=24. Such tumors was localized in breast in 40% of cases (n=16, in ovaries - 20% (n=8, in uterine corpus - 12,5% (n=5, in uterine cervix - 15% (n=6, and in vagina - remaining 12,5% (n=5. Average time from diagnosis to beginning of the treatment was 7,5 months. As a result, the onset of specific therapy was delayed in 65% cases (n=26 and 50% (n=20 underwent unneeded surgery. Diagnostic mistakes lead to inadequate treatment. Extranodal non-Hodgkin’s lymphomas of female reproductive system, both primary and secondary, are rare pathology. Primary lesion is more typical for older women, sec- ondary is mainly affecting younger women (in reproductive period. Chemotherapy response and prognosis are better in primary cases.

B-cell lymphoma of the heart: A rare diagnosis.

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Matos, António P; Palas, João; Doulaptsis, Constantinos; Ramalho, Miguel; Duarte, Sérgio; Bogaert, Jan

2014-12-01

We present a case of a primary cardiac lymphoma in a 60-year-old woman. The clinical presentation was non-specific and the diagnosis was suggested by its appearance on multidetector computed tomography. The final diagnosis was achieved by histopathological study and was corroborated by a decrease in tumor volume after targeted chemotherapy. A brief review of the appearance of primary cardiac lymphomas in imaging studies is presented. Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

B lymphoma Moloney murine leukemia virus insertion region 1: An oncogenic mediator in prostate cancer.

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Liu, Qipeng; Li, Qiaqia; Zhu, Sen; Yi, Yang; Cao, Qi

2018-06-01

B lymphoma Moloney murine leukemia virus insertion region 1 (BMI1), a core member of polycomb repressive complex 1 (PRC1), has been intensely investigated in the field of cancer epigenetics for decades. Widely known as a critical regulator in cellular physiology, BMI1 is essential in self-renewal and differentiation in different lineages of stem cells. BMI1 also plays a significant role in cancer etiology for its involvement in pathological progress such as epithelial-mesenchymal transition (EMT) and cancer stem cell maintenance, propagation, and differentiation. Importantly, overexpression of BMI1 is predictive for drug resistance, tumor recurrence, and eventual therapy failure of various cancer subtypes, which renders the pharmacological targeting at BMI1 as a novel and promising therapeutic approach. The study on prostate cancer, a prevalent hormone-related cancer among men, has promoted enormous research advancements in cancer genetics and epigenetics. This review summarizes the role of BMI1 as an oncogenic and epigenetic regulator in tumor initiation, progression, and relapse of prostate cancer.

Low-Dose Radiation Treatment in Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma: A Plausible Approach? A Single-Institution Experience in 10 Patients

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Girinsky, Theodore, E-mail: girinsky@igr.fr [Department of Radiation Oncology, Institut Gustave Roussy, Villejuif (France); Paumier, Amaury [Department of Radiation Oncology, Institut Gustave Roussy, Villejuif (France); Ferme, Christophe; Hanna, Colette; Ribrag, Vincent [Department of Hematology, Institut Gustave Roussy, Villejuif (France); Leroy-Ladurie, Francois [Department of Thoracic Surgery, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson (France); Ghalibafian, Mithra [Department of Radiation Oncology, Institut Gustave Roussy, Villejuif (France)

2012-07-01

Purpose: To propose an alternative approach for treatment of pulmonary marginal zone lymphoma, using a very small radiation dose (2 Multiplication-Sign 2 Gy) delivered exclusively to tumor sites. Methods and Materials: Patients had localized pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma according to the World Health Organization classification. The 6-MV radiation treatments were delivered using tumor-limited fields, except in cases of diffuse bilateral involvement. Two daily fractions of 2 Gy were delivered to tumor-limited fields using a 6-MV linear accelerator. Results: Ten patients with pulmonary MALT lymphoma entered the study. All but 1 had localized tumor masses. The median follow-up was 56 months (range, 2-103 months). Complete remission or an unconfirmed complete remission was obtained in 60% of patients within the first 2 months, and two additional partial responses were converted into a long-term unconfirmed complete remission. All patients are well and alive, no local progression was observed, and the 5-year progression-free survival rate was 87.5% (95% confidence interval 49%-97%). Conclusions: Our results suggest that extremely low radiation doses delivered exclusively to tumor sites might be a treatment option in pulmonary MALT lymphoma.

Low-Dose Radiation Treatment in Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma: A Plausible Approach? A Single-Institution Experience in 10 Patients

International Nuclear Information System (INIS)

Girinsky, Theodore; Paumier, Amaury; Ferme, Christophe; Hanna, Colette; Ribrag, Vincent; Leroy-Ladurie, François; Ghalibafian, Mithra

2012-01-01

Purpose: To propose an alternative approach for treatment of pulmonary marginal zone lymphoma, using a very small radiation dose (2 × 2 Gy) delivered exclusively to tumor sites. Methods and Materials: Patients had localized pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma according to the World Health Organization classification. The 6-MV radiation treatments were delivered using tumor-limited fields, except in cases of diffuse bilateral involvement. Two daily fractions of 2 Gy were delivered to tumor-limited fields using a 6-MV linear accelerator. Results: Ten patients with pulmonary MALT lymphoma entered the study. All but 1 had localized tumor masses. The median follow-up was 56 months (range, 2–103 months). Complete remission or an unconfirmed complete remission was obtained in 60% of patients within the first 2 months, and two additional partial responses were converted into a long-term unconfirmed complete remission. All patients are well and alive, no local progression was observed, and the 5-year progression-free survival rate was 87.5% (95% confidence interval 49%–97%). Conclusions: Our results suggest that extremely low radiation doses delivered exclusively to tumor sites might be a treatment option in pulmonary MALT lymphoma.

[Relationship between sensitivity of tumor cells to chemotherapeutic agent in vivo and in vitro: experiment with mouse lymphoma cells].

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Li, Chuan-gang; Li, Mo-lin; Shu, Xiao-hong; Jia, Yu-jie; Liu, Yong-ji; Li, Ming

2007-06-12

To study the relationship of the sensitivity of tumor cells to chemotherapeutic agent between in vivo and in vitro. Mouse lymphoma cells of the line E14 were cultured and melphalan resistant EL4 cell line (EL4/melphalan) was established by culturing EL4 cells with continuous low-concentration and intermittent gradually-increasing-concentration of melphalan in vitro. MTT assay was used to evaluate the drug sensitivity and the resistance index of the EL4/melphalan cells to melphalan was calculated. EL4/melphalan and EL4 cells of the concentration of 5 x 10(8)/L were inoculated separately into 20 C57BL/6 mice subcutaneously. 12 days later, the EL4 and EL4/melphalan tumor-bearing mice were randomly divided into 2 groups respectively, 5 mice in each group. Treatment groups were given 7.5 mg/kg melphalan intraperitoneally, and control groups were given the same volume of normal saline. The tumor size was observed every other day. Compared with the EL4 cells, the EL4/melphalan cells had no obvious changes morphologically. They could grow in RPMI 1640 medium containing 5 mg/ml melphalan. The resistance index was 2.87 against melphalan. After the treatment of melphalan of the dose 7.5 mg/kg, the tumor sizes of the treatment groups and control groups inoculated with both EL4 cells and the EL4/melphalan cells gradually decreased at the similar speed, and about one week later all tumors disappeared. However, the tumors of the control groups grew progressively and all the mice died at last. The chemotherapeutic effects of tumors in vivo have nothing to do with the effects of the chemotherapeutic agents on tumor cells in vitro. The tumor cells resistant to melphalan in vitro remain sensitive to the drug in vivo.

Non-Hodgkin's lymphoma - Part II: Management of primary extranodal lymphomas, generalized disease and salvage treatment

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Gospodarowicz, Mary K.; Sutcliffe, Simon B.

1996-01-01

Objective: To review the approach to the diagnosis, classification, assessment, treatment and continuing management of patients with primary extranodal non-Hodgkin's lymphoma, and the management of generalized disease with the emphasis on the current role of salvage treatment with high dose chemotherapy and stem cell/bone marrow support strategies. Non-Hodgkin's lymphoma may involve any part of the body. Many lymphomas, such as MALT, angiocentric T-cell, etc., commonly present in extranodal sites. Lymphomas presenting in the GI tract, and head and neck, are most common with the single most common site being the stomach. Gastric lymphoma is associated with Helicobacter pylorii and is most common in areas endemic for Helicobacter pylorii infection. Recent advances in the understanding of the etiology of gastric MALT, thyroid, and intestinal lymphomas present new opportunities for the application of novel therapeutic approaches e.g. antibiotic therapy for Helicobacter pylori and early stage IPSID. Lymphomas presenting in the orbit, thyroid, breast, bone, extradural and skin are of interest because of the importance of expert RT in securing local control. Primary brain lymphomas present a particular challenge to the radiation oncologist. Although localized, primary brain lymphomas are extremely difficult to control. Rare sites of extranodal lymphoma include testis, female genital tract, and lung. Extranodal lymphomas are often localized and cure with RT or CMT is possible. They represent a assorted group of diseases with diverse presentations, prognosis, sensitivity to RT and expected outcome. They are of particular importance to radiation oncologists as they require special attention to patterns of spread and treatment planning. The principles of management of primary extranodal lymphoma, however, follow those applicable to localized nodal presentations. Although primary extranodal lymphomas are highly curable, a proportion of patients will fail with disseminated

Individualized management of follicular lymphoma.

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Bai, Bing; Huang, Hui-Qiang

2015-03-01

Follicular lymphoma (FL) is the most common indolent non-hodgkin lymphoma. Most patients with FL are diagnosed with advanced disease and are considered incurable. The classical prognostic index in FL is the FL international prognostic index (FLIPI). The management of FL is mainly determined by histologic grading, clinical stage, and tumor burden. For patients with stage I and II disease, an involved-site radiation therapy (ISRT) is recommended and may be potentially curative approach with 60% to 80% of 10-year overall survival (OS) rates, while patients with stage III and IV should be treated with systemic therapy. The watchful waiting is still an option for patients without symptoms or/and low tumor burden. Induction of immuno-chemotherapy combined with consolidation of rituximab maintenance (MR) is standard care for patients with symptomatic disease or with high tumor burden when treatment indicated. The major indication for systemic therapy is including candidate for clinical trials, threatened end organ function, cytopenia secondary to lymphoma bulky disease and steady progress etc. at present time. Routine baseline and regular hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (HBcAb) testing is strongly recommended for all patients before the initiation of immuno-chemotherapy in order to minimize the risk of hepatitis B virus (HBV) reactivation which has been observed approximately 20% to 50% of patients with positive HBsAg and 3% to 45% of patients with positive HBcAb. Prophylactic antiviral treatment in patients who are HBsAg-positive or HBcAb-positive is indicated before immuno-chemotherapy. The management for elderly patients should be carefully selected to avoid overtreatment and severe toxicities. Individualized dose adjustment for chemotherapy and an adequate supportive treatment are essential for this special population. Novel agents such as lenalidomide, ibrutinib and idelalisib are promising. In conclusion, individualized management

Primary B-cell Lymphoma of the Thyroid Featuring the Different Ultrasonographic Findings

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Kim, Ji Na; Choi, Yoon Jung; Kim, Dong Hoon [Kangbuk Samsung Medical Center, Seoul (Korea, Republic of)

2009-06-15

We review here 3 cases of primary thyroid lymphoma that we experienced during the past 5 years (age range: 39-55, all of the patients were female). The clinical and various ultrasonographic characteristics together with the other imaging modalities of primary thyroid lymphomas are described. The clinical features at presentation for one patient were a goiter with rapid growth and this was accompanied by compressive symptoms. The tumors of the other 2 patients were incidentally found during screening thyroid ultrasound exams. The pathologic studies of 2 cases showed a diffuse B-cell lymphoma with associated Hashimoto's thyroiditis and one case was a B-cell lymphoma of the MALT type. An extra-thyroid extension was shown in one case. The treatments included surgery alone for two cases, and chemotherapy and radiation therapy for one case. A US exam of thyroid lymphoma can show various morphological features, and US-CNB is helpful for diagnosing thyroid lymphoma.

Primary extranodal lymphomas - spectrum of distribution and morphology with immunophenotyping: A 3-year institutional study

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Chinnam Aparna

2015-01-01

Full Text Available Background: Malignant lymphomas arising in extranodal sites are intriguing. The histological types of lymphomas vary from one site to another. This study is undertaken to diagnose and categorize extranodal lymphomas using histochemistry and immunohistochemistry (IHC. Materials and Methods: Formalin processed paraffin blocks and hematoxylin and eosin stained sections were used for routine histology. IHC was done in all cases. Results: We have encountered 31 cases of extra nodal lymphomas over a period of 3 years. The tumors occurred at different sites, including brain, nasopharynx, nose, gastrointestinal tract, thyroid, bone, testis, breast, lung, vagina, and skin. Majority of the cases were B-cell lymphomas, while four cases were T-cell lymphomas. Among the B-cell lymphomas diffuse large B-cell lymphoma was the most common variant. Conclusion: This study reiterates the key role of IHC particularly when the differential diagnosis includes an undifferentiated epithelial malignancy and a high-grade lymphoma in the extranodal sites as the treatment modalities and prognosis are different.

Nonviral gene therapy in vivo with PAM-RG4/apoptin as a potential brain tumor therapeutic.

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An, Songhie; Nam, Kihoon; Choi, Sunghyun; Bai, Cheng Z; Lee, Yan; Park, Jong-Sang

2013-01-01

Glioma is still one of the most complicated forms of brain tumor to remove completely due to its location and the lack of an efficient means to specifically eliminate tumor cells. For these reasons, this study has examined the effectiveness of a nonviral gene therapy approach utilizing a tumor-selective killer gene on a brain tumor xenograft model. The therapeutic apoptin gene was recombined into the JDK plasmid and delivered into human brain tumor cells (U87MG) by using a polyamidoamine dendrimer with an arginine surface (PAM-RG4). Studies in vitro showed that the PAM-RG4/apoptin plasmid polyplex exhibited a particularly high transfection activity of .40%. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, 4',6-Diamidino-2-phenylindole (DAPI) TUNEL assay, DAPI staining, and caspase-3 activity assay verified that the tumor cells had undergone apoptosis induced by apoptin. For in vivo studies, the polyplex was injected into tumors, which were induced by injecting U87MG cells intradermally into nude mice. Based on hematoxylin and eosin staining, epidermal growth factor receptor immunohistochemistry results and tumor volume measurement results, tumor growth was effectively inhibited and no specific edema, irritation, or other harm to the skin was observed after polyplex injection. The in vivo expression of apoptin and the induction of apoptosis were verified by reverse-transcription polymerase chain reaction analysis, TUNEL assay, and DAPI staining. The PAM-RG4/apoptin gene polyplex is a strong candidate for brain tumor therapeutics because of the synergistic effect of the carrier's high transfection efficiency (35%-40%) in glioma cells and the selective apoptosis-inducing activity of apoptin in tumor cells.

Primary NK/T cell lymphoma nasal type of the colon

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Ana María Chirife

2013-02-01

Full Text Available Since nasal NK/T-cell lymphoma and NK/T-cell lymphoma nasal type are rare diseases, colonic involvement has seldom been seen. We report a case of a patient with a primary NK/T-cell lymphoma nasal type of the colon. The patient had no history of malignant diseases and was diagnosed after exhaustive study in the context of fever of unknown origin. The first therapeutic approach followed the DAEPOCH-protocol: etoposide, prednisone, doxor-rubicin, vincristine and cyclophosphamide. The persistence of constitutional symptoms after the first treatment course motivated the switch to a second line following the SMILE-protocol: dexamethasone, metotrexate, ifosfamide, E.coli L-asparaginase, and etoposide. Despite intensive chemotherapy, the patient died 2 months after the diagnose of an extranodal NK/T-cell lymphoma of the colon and 4 months after the first symptomatic appearance of disease.

TNFRSF14 aberrations in follicular lymphoma increase clinically significant allogeneic T-cell responses.

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Kotsiou, Eleni; Okosun, Jessica; Besley, Caroline; Iqbal, Sameena; Matthews, Janet; Fitzgibbon, Jude; Gribben, John G; Davies, Jeffrey K

2016-07-07

Donor T-cell immune responses can eradicate lymphomas after allogeneic hematopoietic stem cell transplantation (AHSCT), but can also damage healthy tissues resulting in harmful graft-versus-host disease (GVHD). Next-generation sequencing has recently identified many new genetic lesions in follicular lymphoma (FL). One such gene, tumor necrosis factor receptor superfamily 14 (TNFRSF14), abnormal in 40% of FL patients, encodes the herpes virus entry mediator (HVEM) which limits T-cell activation via ligation of the B- and T-lymphocyte attenuator. As lymphoma B cells can act as antigen-presenting cells, we hypothesized that TNFRSF14 aberrations that reduce HVEM expression could alter the capacity of FL B cells to stimulate allogeneic T-cell responses and impact the outcome of AHSCT. In an in vitro model of alloreactivity, human lymphoma B cells with TNFRSF14 aberrations had reduced HVEM expression and greater alloantigen-presenting capacity than wild-type lymphoma B cells. The increased immune-stimulatory capacity of lymphoma B cells with TNFRSF14 aberrations had clinical relevance, associating with higher incidence of acute GVHD in patients undergoing AHSCT. FL patients with TNFRSF14 aberrations may benefit from more aggressive immunosuppression to reduce harmful GVHD after transplantation. Importantly, this study is the first to demonstrate the impact of an acquired genetic lesion on the capacity of tumor cells to stimulate allogeneic T-cell immune responses which may have wider consequences for adoptive immunotherapy strategies. © 2016 by The American Society of Hematology.

Lymphoma: current status of clinical and preclinical imaging with radiolabeled antibodies

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England, Christopher G. [University of Wisconsin School of Medicine and Public Health, Department of Medical Physics, Madison, WI (United States); Rui, Lixin [University of Wisconsin School of Medicine and Public Health, Department of Medicine, Madison, WI (United States); University of Wisconsin School of Medicine and Public Health, Carbone Cancer Center, Madison, WI (United States); Cai, Weibo [University of Wisconsin School of Medicine and Public Health, Department of Medical Physics, Madison, WI (United States); University of Wisconsin School of Medicine and Public Health, Carbone Cancer Center, Madison, WI (United States); University of Wisconsin School of Medicine and Public Health, Department of Radiology, Madison, WI (United States)

2017-03-15

Lymphoma is a complex disease that arises from cells of the immune system with an intricate pathology. While lymphoma may be classified as Hodgkin or non-Hodgkin, each type of tumor is genetically and phenotypically different and highly invasive tissue biopsies are the only method to investigate these differences. Noninvasive imaging strategies, such as immunoPET, can provide a vital insight into disease staging, monitoring treatment response in patients, and dose planning in radioimmunotherapy. ImmunoPET imaging with radiolabeled antibody-based tracers may also assist physicians in optimizing treatment strategies and enhancing patient stratification. Currently, there are two common biomarkers for molecular imaging of lymphoma, CD20 and CD30, both of which have been considered for investigation in preclinical imaging studies. In this review, we examine the current status of both preclinical and clinical imaging of lymphoma using radiolabeled antibodies. Additionally, we briefly investigate the role of radiolabeled antibodies in lymphoma therapy. As radiolabeled antibodies play critical roles in both imaging and therapy of lymphoma, the development of novel antibodies and the discovery of new biomarkers may greatly affect lymphoma imaging and therapy in the future. (orig.)

Lymphoma: current status of clinical and preclinical imaging with radiolabeled antibodies

International Nuclear Information System (INIS)

England, Christopher G.; Rui, Lixin; Cai, Weibo

2017-01-01

Lymphoma is a complex disease that arises from cells of the immune system with an intricate pathology. While lymphoma may be classified as Hodgkin or non-Hodgkin, each type of tumor is genetically and phenotypically different and highly invasive tissue biopsies are the only method to investigate these differences. Noninvasive imaging strategies, such as immunoPET, can provide a vital insight into disease staging, monitoring treatment response in patients, and dose planning in radioimmunotherapy. ImmunoPET imaging with radiolabeled antibody-based tracers may also assist physicians in optimizing treatment strategies and enhancing patient stratification. Currently, there are two common biomarkers for molecular imaging of lymphoma, CD20 and CD30, both of which have been considered for investigation in preclinical imaging studies. In this review, we examine the current status of both preclinical and clinical imaging of lymphoma using radiolabeled antibodies. Additionally, we briefly investigate the role of radiolabeled antibodies in lymphoma therapy. As radiolabeled antibodies play critical roles in both imaging and therapy of lymphoma, the development of novel antibodies and the discovery of new biomarkers may greatly affect lymphoma imaging and therapy in the future. (orig.)

The histone lysine methyltransferase KMT2D sustains a gene expression program that represses B cell lymphoma development.

Science.gov (United States)

Ortega-Molina, Ana; Boss, Isaac W; Canela, Andres; Pan, Heng; Jiang, Yanwen; Zhao, Chunying; Jiang, Man; Hu, Deqing; Agirre, Xabier; Niesvizky, Itamar; Lee, Ji-Eun; Chen, Hua-Tang; Ennishi, Daisuke; Scott, David W; Mottok, Anja; Hother, Christoffer; Liu, Shichong; Cao, Xing-Jun; Tam, Wayne; Shaknovich, Rita; Garcia, Benjamin A; Gascoyne, Randy D; Ge, Kai; Shilatifard, Ali; Elemento, Olivier; Nussenzweig, Andre; Melnick, Ari M; Wendel, Hans-Guido

2015-10-01

The gene encoding the lysine-specific histone methyltransferase KMT2D has emerged as one of the most frequently mutated genes in follicular lymphoma and diffuse large B cell lymphoma; however, the biological consequences of KMT2D mutations on lymphoma development are not known. Here we show that KMT2D functions as a bona fide tumor suppressor and that its genetic ablation in B cells promotes lymphoma development in mice. KMT2D deficiency also delays germinal center involution and impedes B cell differentiation and class switch recombination. Integrative genomic analyses indicate that KMT2D affects methylation of lysine 4 on histone H3 (H3K4) and expression of a set of genes, including those in the CD40, JAK-STAT, Toll-like receptor and B cell receptor signaling pathways. Notably, other KMT2D target genes include frequently mutated tumor suppressor genes such as TNFAIP3, SOCS3 and TNFRSF14. Therefore, KMT2D mutations may promote malignant outgrowth by perturbing the expression of tumor suppressor genes that control B cell-activating pathways.

Quantitative Apparent Diffusion Coefficients in the Characterization of Brain Tumors and Associated Peritumoral Edema

International Nuclear Information System (INIS)

Server, A.; Schellhorn, T.; Nakstad, P.H.; Kulle, B.; Maehlen, J.; Kumar, T.; Josefsen, R.; Langberg, C.W.

2009-01-01

Background: Conventional magnetic resonance (MR) imaging has a number of limitations in the diagnosis of the most common intracranial brain tumors, including tumor specification and the detection of tumoral infiltration in regions of peritumoral edema. Purpose: To prospectively assess if diffusion-weighted MR imaging (DWI) could be used to differentiate between different types of brain tumors and to distinguish between peritumoral infiltration in high-grade gliomas, lymphomas, and pure vasogenic edema in metastases and meningiomas. Material and Methods: MR imaging and DWI was performed on 93 patients with newly diagnosed brain tumors: 59 patients had histologically verified high-grade gliomas (37 glioblastomas multiforme, 22 anaplastic astrocytomas), 23 patients had metastatic brain tumors, five patients had primary cerebral lymphomas, and six patients had meningiomas. Apparent diffusion coefficient (ADC) values of tumor (enhancing regions or the solid portion of tumor) and peritumoral edema, and ADC ratios (ADC of tumor or peritumoral edema to ADC of contralateral white matter, ADC of tumor to ADC of peritumoral edema) were compared with the histologic diagnosis. ADC values and ratios of high-grade gliomas, primary cerebral lymphomas, metastases, and meningiomas were compared by using ANOVA and multiple comparisons. Optimal thresholds of ADC values and ADC ratios for distinguishing high-grade gliomas from metastases were determined by receiver operating characteristic (ROC) curve analysis. Results: Statistically significant differences were found for minimum and mean of ADC tumor and ADC tumor ratio values between metastases and high-grade gliomas when including only one factor at a time. Including a combination of in total four parameters (mean ADC tumor, and minimum, maximum and mean ADC tumor ratio) resulted in sensitivity, specificity, positive (PPV), and negative predictive values (NPV) of 72.9, 82.6, 91.5, and 54.3% respectively. In the ROC curve analysis

Primary malignant small bowel tumor

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Oh, Kyung Seung; Suh, Ho Jong; Kim, So Sun; Kim, Ho Joon; Chun, Byung Hee; Joh, Young Duk [Kosin College, Pusan (Korea, Republic of)

1990-07-15

Small bowel tumors are rarely detected unless there is intestinal obstruction or bleeding. In the seven years 1982-1988, at Kosin Medical Center, 25 primary malignant small bowel tumors were studied radiographically with barium and / or computed tomography (CT). CT revealed gastrointestinal abnormalities in 20 patients. In ten, lesion were identified by upper G-I series, in 15 by small bowel series, and in addition, in 3 by colon enema. The most common malignant small bowel tumor was adenocarcinoma (N=15) and was next common lymphoma (N=7). On barium study, primary adenocarcinoma appeared as an irregular stricture (66.7%) and polypoid mass with intussusception was most prominent finding in lymphoma. Leiomyosarcoma appeared as an exophytic mass with excavation or ulceration. CT was found to be accurate in detecting wall thickening, complications and other associated findings. In conclusion, barium study was useful in the diagnosis of primary malignant small bowel tumor and CT was more accurate in detecting secondary findings.

Primary malignant small bowel tumor

International Nuclear Information System (INIS)

Oh, Kyung Seung; Suh, Ho Jong; Kim, So Sun; Kim, Ho Joon; Chun, Byung Hee; Joh, Young Duk

1990-01-01

Small bowel tumors are rarely detected unless there is intestinal obstruction or bleeding. In the seven years 1982-1988, at Kosin Medical Center, 25 primary malignant small bowel tumors were studied radiographically with barium and / or computed tomography (CT). CT revealed gastrointestinal abnormalities in 20 patients. In ten, lesion were identified by upper G-I series, in 15 by small bowel series, and in addition, in 3 by colon enema. The most common malignant small bowel tumor was adenocarcinoma (N=15) and was next common lymphoma (N=7). On barium study, primary adenocarcinoma appeared as an irregular stricture (66.7%) and polypoid mass with intussusception was most prominent finding in lymphoma. Leiomyosarcoma appeared as an exophytic mass with excavation or ulceration. CT was found to be accurate in detecting wall thickening, complications and other associated findings. In conclusion, barium study was useful in the diagnosis of primary malignant small bowel tumor and CT was more accurate in detecting secondary findings

[Study of the immunological mechanism of anti-tumor effects of 5-FU by establishing EL4 tumor-bearing mouse models].

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Li, Mo-Lin; Li, Chuan-Gang; Shu, Xiao-Hong; Li, Ming-Xia; Jia, Yu-Jie; Qin, Zhi-Hai

2007-11-01

To investigate the immunological mechanism of anti-tumor effect of 5-FU by establishing lymphoma EL4 tumor-bearing mouse models in wild type C57BL/6 mice and nude C57BL/6 mice, respectively. The mouse lymphoma EL4 cells were inoculated subcutaneously into wild type C57BL/6 mice (immune-competent mice). Twelve days later, 5-FU of different doses was administered intraperitoneally to treat these wild type C57BL/6 tumor-bearing mice. The size of tumors in the wild type C57BL/6 mice was observed and recorded to explore the minimal dose of 5-FU that could cure the tumor-bearing mice. Then the same amount of EL4 tumor cells was inoculated subcutaneously into wild type C57BL/6 mice and nude C57BL/6 mice (T cell-deficient mice) simultaneously, which had the same genetic background of C57BL/6. Twelve days later, 5-FU of the minimal dose was given intraperitoneally to treat both the wild type and nude C57BL/6 tumor-bearing mice. The size of tumors in the two different types of mice was observed and recorded. A single dose of 5-FU (75 mg/kg) cured both the EL4 tumor-bearing wild type C57BL/6 mice and the EL4 tumor-bearing nude C57BL/6 mice in the first week. Two weeks after 5-FU treatment, all of the nude mice died of tumor relapse while most of the wild type C57BL/6 mice were fully recovered. A single dose of 5-FU has marked anti-tumor effects on lymphoma EL4 tumor-bearing C57BL/6 mice with or without T lymphocytes. The relapse of tumors after 5-FU treatment might be related to the function of T lymphocytes.

[Establishment of EL4 tumor-bearing mouse models and investigation on immunological mechanisms of anti-tumor effect of melphalan].

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Li, Mo-lin; Li, Chuan-gang; Shu, Xiao-hong; Jia, Yu-jie; Qin, Zhi-hai

2006-03-01

To establish mouse lymphoma EL4 tumor-bearing mouse models in wild type C57BL/6 mice and nude C57BL/6 mice respectively, and to further investigate the immunological mechanisms of anti-tumor effect of melphalan. Mouse lymphoma EL4 cells were inoculated subcutaneously into wild type C57BL/6 mice (immune-competent mice). Twelve days later, melphalan of different doses were administered intraperitoneally to treat these wild type C57BL/6 tuomr-bearing mice. Tumor sizes were observed and recorded subsequently to find out the minimal dose of melphalan that could cure the tuomr-bearing mice. Then the same amount of EL4 tumor cells were inoculated subcutaneously into wild type C57BL/6 mice and nude C57BL/6 mice (T cell-deficient mice) simultaneously, which had the same genetic background of C57BL/6. Twelve days later, melphalan of the minimal dose was given intraperitoneally to treat both the wild type and nude C57BL/6 tuomr-bearing mice. Tumor sizes were observed and recorded in these two different types of mice subsequently. A single dose of melphalan (7.5 mg/kg) could cure EL4 tumor-bearing wild type C57BL/6 mice, but could not induce tumor regression in EL4 tumor-bearing nude C57BL/6 mice. A single dose of melphalan has obvious anti-tumor effect on mouse lymphoma EL4 tumor-bearing wild type C57BL/6mice, which requires the involvement of T lymphocytes in the host probably related to their killing functions.

Prognostic value of baseline metabolic tumor volume in early stage Hodgkin's lymphoma in the standard arm of H10 trial

DEFF Research Database (Denmark)

Cottereau, Anne Ségolène; Versari, Annibale; Loft, Annika

2018-01-01

and compared to baseline characteristics, staging classifications and iPET2. A total of 258 patients were eligible, 101 favorable and 157 unfavorable. The median follow-up was 55 months, with 27 PFS and 12 OS events. TMTV was prognosticator of PFS (p...We tested baseline PET/CT as a measure of total tumor burden in order to better identify high risk patients in early-stage Hodgkin's lymphoma (HL). Stage I-II HL patients enrolled in the standard arm (combined modality treatment) of the H10 trial (NCT00433433) with available baseline PET...... and interim PET (iPET2) after two cycles of doxorubicine, bleomycin, vinblastine, dacarbazine were included. Total metabolic tumor volume (TMTV) was measured on baseline PET. IPET2 findings were reported negative (DS1-3) or positive (DS4-5) with the Deauville scale. The prognostic value of TMTV was evaluated...

Diagnosing lymphoma in a setting with a high burden of infection: a pediatric case of Epstein-Barr virus-associated aggressive B-cell lymphoma with t(8;14 (q23;q32 and extensive necrosis mimicking tuberculosis

Directory of Open Access Journals (Sweden)

Mário Henrique Magalhães Barros

2015-02-01

Full Text Available The association of lymphoma with necrotic granuloma can pose diagnostic challenges and delay treatment, especially in settings with a high burden of infection. In these settings, the timely use of cytogenetic and molecular methods is most relevant. Here, we report a case of B-cell lymphoma with t (8;14 in a 5-year-old male child. The lymphoma was associated with necrotic granuloma and was initially misdiagnosed as tuberculosis. Polymerase chain reaction was used to detect clonal lymphoproliferation and to rule out Mycobacterium tuberculosis infection. Tumor cells harbored Epstein-Barr virus and expressed CD20, CD10, BCL6, and Ki67 (30%, leading to the diagnosis of B-cell lymphoma with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma.

Targeting Potassium Channels for Increasing Delivery of Imaging Agents and Therapeutics to Brain Tumors

OpenAIRE

Nagendra Sanyasihally Ningaraj; Divya eKhaitan

2013-01-01

Every year in the US, 20,000 new primary and nearly 200,000 metastatic brain tumor cases are reported. The cerebral microvessels/ capillaries that form the blood–brain barrier (BBB) not only protect the brain from toxic agents in the blood but also pose a significant hindrance to the delivery of small and large therapeutic molecules. Different strategies have been employed to circumvent the physiological barrier posed by blood-brain tumor barrier (BTB). Studies in our laboratory have identifi...

Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics

NARCIS (Netherlands)

Schmitz, Roland; Young, Ryan M.; Ceribelli, Michele; Jhavar, Sameer; Xiao, Wenming; Zhang, Meili; Wright, George; Shaffer, Arthur L.; Hodson, Daniel J.; Buras, Eric; Liu, Xuelu; Powell, John; Yang, Yandan; Xu, Weihong; Zhao, Hong; Kohlhammer, Holger; Rosenwald, Andreas; Kluin, Philip; Mueller-Hermelink, Hans Konrad; Ott, German; Gascoyne, Randy D.; Connors, Joseph M.; Rimsza, Lisa M.; Campo, Elias; Jaffe, Elaine S.; Delabie, Jan; Smeland, Erlend B.; Ogwang, Martin D.; Reynolds, Steven J.; Fisher, Richard I.; Braziel, Rita M.; Tubbs, Raymond R.; Cook, James R.; Weisenburger, Dennis D.; Chan, Wing C.; Pittaluga, Stefania; Wilson, Wyndham; Waldmann, Thomas A.; Rowe, Martin; Mbulaiteye, Sam M.; Rickinson, Alan B.; Staudt, Louis M.

2012-01-01

Burkitt's lymphoma (BL) can often be cured by intensive chemotherapy, but the toxicity of such therapy precludes its use in the elderly and in patients with endemic BL in developing countries, necessitating new strategies(1). The normal germinal centre B cell is the presumed cell of origin for both

Promising novel therapeutic approaches in the management of gastrointestinal stromal tumors.

Science.gov (United States)

Szucs, Zoltan; Thway, Khin; Fisher, Cyril; Bulusu, Ramesh; Constantinidou, Anastasia; Benson, Charlotte; van der Graaf, Winette Ta; Jones, Robin L

2017-01-01

Primary and secondary resistance to currently available licensed tyrosine kinase inhibitors poses a real clinical challenge in the management of advanced gastrointestinal stromal tumors. Within the frame of early phase clinical trials novel systemic treatments are currently being evaluated to target both the well explored and novel emerging downstream effectors of KIT and PDGFRA signaling. Alternative therapeutic approaches also include exploring novel inhibitors of the KIT/PDGFRA receptors, immune checkpoint and cyclin-dependent kinase inhibitors. The final clinical trial outcome data for these agents are highly anticipated. Integration of new diagnostic techniques into routine clinical practice can potentially guide tailored delivery of agents in the treatment of a highly polyclonal, heterogeneous disease such as heavily pretreated advanced gastrointestinal stromal tumor.

In vivo efficacy of the Bcl-2 antagonist ABT-737 against aggressive Myc-driven lymphomas

OpenAIRE

Mason, Kylie D.; Vandenberg, Cassandra J.; Scott, Clare L.; Wei, Andrew H.; Cory, Suzanne; Huang, David C. S.; Roberts, Andrew W.

2008-01-01

Deregulated Myc expression drives many human cancers, including Burkitt's lymphoma and a highly aggressive subset of diffuse large cell lymphomas. Myc-driven tumors often display resistance to chemotherapeutics because of acquisition of mutations that impair the apoptosis pathway regulated by the Bcl-2 protein family. Given the need to identify new therapies for such lymphomas, we have evaluated the efficacy of ABT-737, a small molecule that mimics the action of the BH3-only proteins, natural...

Human bone marrow mesenchymal stem cells display anti-cancer activity in SCID mice bearing disseminated non-Hodgkin's lymphoma xenografts.

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Paola Secchiero

Full Text Available BACKGROUND: Although multimodality treatment can induce high rate of remission in many subtypes of non-Hodgkin's lymphoma (NHL, significant proportions of patients relapse with incurable disease. The effect of human bone marrow (BM mesenchymal stem cells (MSC on tumor cell growth is controversial, and no specific information is available on the effect of BM-MSC on NHL. METHODOLOGY/PRINCIPAL FINDINGS: The effect of BM-MSC was analyzed in two in vivo models of disseminated non-Hodgkin's lymphomas with an indolent (EBV(- Burkitt-type BJAB, median survival = 46 days and an aggressive (EBV(+ B lymphoblastoid SKW6.4, median survival = 27 days behavior in nude-SCID mice. Intra-peritoneal (i.p. injection of MSC (4 days after i.p. injection of lymphoma cells significantly increased the overall survival at an optimal MSC:lymphoma ratio of 1:10 in both xenograft models (BJAB+MSC, median survival = 58.5 days; SKW6.4+MSC, median survival = 40 days. Upon MSC injection, i.p. tumor masses developed more slowly and, at the histopathological observation, exhibited a massive stromal infiltration coupled to extensive intra-tumor necrosis. In in vitro experiments, we found that: i MSC/lymphoma co-cultures modestly affected lymphoma cell survival and were characterized by increased release of pro-angiogenic cytokines with respect to the MSC, or lymphoma, cultures; ii MSC induce the migration of endothelial cells in transwell assays, but promoted endothelial cell apoptosis in direct MSC/endothelial cell co-cultures. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate that BM-MSC exhibit anti-lymphoma activity in two distinct xenograft SCID mouse models of disseminated NHL.

Association of Hodgkin's lymphoma with Epstein Barr virus infection

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Elmir Čičkušić

2007-02-01

Full Text Available The role of Epstein Barr virus (EBV in the onset of Hodgkin's lymphoma has been a subject of ongoing research. However, confirmation of EBV oncogenic involvement was not possible due to the small number of neoplastic cells characteristic for this type of tumor. Presence of EBV infection in neoplastic and non-neoplastic cells was analyzed in 81 cases of Hodgkin's lymphoma. In neoplastic cells, using an immunohistochemical method, latent membrane protein 1 (LMP1 was found in 33,3% of cases, while in situ hybridization results demonstrated the presence of EBER RNA in 48,1% of the cases. EBER RNA was found in non-neoplastic lymphocytes in 38,3% of cases. EBV is most frequently associated with Hodgkin's lymphoma in the first and seventh decade of life, specifically the nodular sclerosis subtype. No apparent difference was observed in the association of Hodgkin's lymphoma with EBV between genders, or in relation to clinical stage of the disease and average age of the patient. However, association with childhood age is significantly greater in comparison to adults. EBV associated disease shows a significantly greater prevalence in T lymphocytes. Slightly more abundant are cytotoxic T lymphocytes, which are also more frequently in contact with Reed-Sternberg cells, although there is no difference in number and positioning of histiocytes. Variations between the data on the association of EBV with Hodgkin's lymphoma among studies from different parts of the world suggest that factors of age, gender, ethnic background and social status might present biological modifiers of EBV influence on the pathogenesis of this neoplasm. The differences in non-neoplastic infiltrate EBV+ and EBV- lymphoma indicate the effect of the virus on the immune interaction of tumor and host in this disease.

Lymphoma classification update: B-cell non-Hodgkin lymphomas.

Science.gov (United States)

Jiang, Manli; Bennani, N Nora; Feldman, Andrew L

2017-05-01

Lymphomas are classified based on the normal counterpart, or cell of origin, from which they arise. Because lymphocytes have physiologic immune functions that vary both by lineage and by stage of differentiation, the classification of lymphomas arising from these normal lymphoid populations is complex. Recent genomic data have contributed additional complexity. Areas covered: Lymphoma classification follows the World Health Organization (WHO) system, which reflects international consensus and is based on pathological, genetic, and clinical factors. A 2016 revision to the WHO classification of lymphoid neoplasms recently was reported. The present review focuses on B-cell non-Hodgkin lymphomas, the most common group of lymphomas, and summarizes recent changes most relevant to hematologists and other clinicians who care for lymphoma patients. Expert commentary: Lymphoma classification is a continually evolving field that needs to be responsive to new clinical, pathological, and molecular understanding of lymphoid neoplasia. Among the entities covered in this review, the 2016 revision of the WHO classification particularly impact the subclassification and genetic stratification of diffuse large B-cell lymphoma and high-grade B-cell lymphomas, and reflect evolving criteria and nomenclature for indolent B-cell lymphomas and lymphoproliferative disorders.

Advances in Primary Central Nervous System Lymphoma.

Science.gov (United States)

Patrick, Lauren B; Mohile, Nimish A

2015-12-01

Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma that is limited to the CNS. Although novel imaging techniques aid in discriminating lymphoma from other brain tumors, definitive diagnosis requires brain biopsy, vitreoretinal biopsy, or cerebrospinal fluid analysis. Survival rates in clinical studies have improved over the past 20 years due to the addition of high-dose methotrexate-based chemotherapy regimens to whole-brain radiotherapy. Long-term survival, however, is complicated by clinically devastating delayed neurotoxicity. Newer regimens are attempting to reduce or eliminate radiotherapy from first-line treatment with chemotherapy dose intensification. Significant advances have also been made in the fields of pathobiology and treatment, with more targeted treatments on the horizon. The rarity of the disease makes conducting of prospective clinical trials challenging, requiring collaborative efforts between institutions. This review highlights recent advances in the biology, detection, and treatment of PCNSL in immunocompetent patients.

Repeated tumor pO2 measurements by multi-site EPR oximetry as a prognostic marker for enhanced therapeutic efficacy of fractionated radiotherapy

International Nuclear Information System (INIS)

Hou Huagang; Lariviere, Jean P.; Demidenko, Eugene; Gladstone, David; Swartz, Harold; Khan, Nadeem

2009-01-01

Purpose: To investigate the temporal effects of single or fractionated radiotherapy on subcutaneous RIF-1 tumor pO 2 and to determine the therapeutic outcomes when the timing of fractionations is guided by tumor pO 2 . Methods: The time-course of the tumor pO 2 changes was followed by multi-site electron paramagnetic resonance (EPR) oximetry. The tumors were treated with single 10, 20, and 10 Gy x 2 doses, and the tumor pO 2 was measured repeatedly for six consecutive days. In the 10 Gy x 2 group, the second dose of 10 Gy was delivered at a time when the tumors were either relatively oxygenated or hypoxic. The changes in tumor volumes were followed for nine days to determine the therapeutic outcomes. Results: A significant increase in tumor pO 2 was observed at 24 h post 10 Gy, while 20 Gy resulted in a significant increase in tumor pO 2 at 72-120 h post irradiation. The tumors irradiated with a second dose of 10 Gy at 24 h, when the tumors were oxygenated, had a significant increase in tumor doubling times (DTs), as compared to tumors treated at 48 h when they were hypoxic (p 2 repeatedly during fractionated schemes to optimize radiotherapeutic outcome. This technique could also be used to identify responsive and non-responsive tumors, which will facilitate the design of other therapeutic approaches for non-responsive tumors at early time points during the course of therapy.

Pembrolizumab and Vorinostat in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, or Hodgkin Lymphoma

Science.gov (United States)

2018-04-23

Grade 3a Follicular Lymphoma; Grade 3b Follicular Lymphoma; Recurrent Classical Hodgkin Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory Classical Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma

Insights into the Molecular Pathogenesis of Activated B-Cell-like Diffuse Large B-Cell Lymphoma and Its Therapeutic Implications

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Georg Lenz

2015-05-01

Full Text Available Within the last couple of years, the understanding of the molecular mechanisms that drive the pathogenesis of diffuse large B-cell lymphoma (DLBCL has significantly improved. Large-scale gene expression profiling studies have led to the discovery of several molecularly defined subtypes that are characterized by specific oncogene addictions and significant differences in their outcome. Next generation sequencing efforts combined with RNA interference screens frequently identify crucial oncogenes that lead to constitutive activation of various signaling pathways that drive lymphomagenesis. This review summarizes our current understanding of the molecular pathogenesis of the activated B-cell-like (ABC DLBCL subtype that is characterized by poor prognosis. A special emphasis is put on findings that might impact therapeutic strategies of affected patients.