Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malignant lymphoma of the female genital tract (FGT) is rare. In this study, 5 peripheral T/natural killer (NK)-cell lymphomas (PTCLs) involving the FGT are reported. They include 2 from the uterus and 1 each from ovary, uterus and ovary, and vagina, and were detected between 1996 and 2000. One of the 2 ovarian tumors was bilateral. In all cases, the FGT was the initial site of clinical presentation of disease. Age at presentation ranged from 21 to 52 years (median, 36 years). One case was stage I disease, 2 were stage II, and 2 were stage IV. All 5 tumors were positive for CD3epsilon, and 3 harbored the Epstein-Barr virus, although the detailed immunophenotypic profiles varied. Three were diagnosed as nasal type T/NK-cell lymphoma, 1 as anaplastic large-cell lymphoma (anaplastic lymphoma kinase [ALK]-positive), and 1 as unspecified PTCL of cytotoxic phenotype, according to the forthcoming World Health Organization classification. Four of 5 patients received laparotomy and chemotherapy. Four patients (in stages II and IV) died of disease within 16 months of the initial diagnosis, whereas only 1 patient (in stage I) is alive without disease at 39 months of follow-up. Our experience in this series provided clinically relevant information on diagnosis, treatment, and outcome for extremely rare tumors of the FGT.
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PMID:Peripheral T/natural killer-cell lymphoma involving the female genital tract: a clinicopathologic study of 5 cases. 1137 45

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of non-Hodgkin lymphomas with a wide spectrum of clinicopathologic features, and apoptosis mechanisms may have a role in lymphomagenesis. We assessed apoptotic rate (AR) in 112 PTCLs using a tissue microarray developed in our laboratory and a modified terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. The mean AR was 1.47% +/- 1.38% for the entire group of PTCLs (range, 0.06%-5.15%), and AR varied significantly among different tumor types. In mycosis fungoides, the mean AR was 0.74%; angioimmunoblastic T-cell lymphoma, 1.02%; PTCL, not otherwise specified, 1.38%; cutaneous anaplastic large cell lymphoma (ALCL), 1.41%; anaplastic lymphoma kinase protein (ALK)-negative ALCL, 1.43%; extranodal natural killer/T-cell lymphoma of nasal type, 2.04%; ALK-positive ALCL, 2.95%; and enteropathy-type T-cell lymphoma, 3.06%. Mean AR was higher in PTCL with large cell vs small/medium cell morphologic features (1.66% +/- 1.1% vs 0.99% +/- 1.0%). In a subset of 33 PTCLs, the tissue microarray results comparedfavorably with those obtained in full tissue sections. We conclude that the highest ARs in PTCLs are found in enteropathy-type T-cell lymphoma and ALK-positive ALCL, and that AR can be assessed reliably by using a tissue microarray.
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PMID:Apoptotic rate in peripheral T-cell lymphomas. A study using a tissue microarray with validation on full tissue sections. 1221 74

Peripheral T-cell lymphoma primary to the central nervous system is a rare occurrence. The authors report a case of an 89-year-old woman who presented with a 3-month history of worsening confusion and recent onset of headache, nausea and vomiting, and upper limb tremors. Computed tomography and magnetic resonance imaging examinations demonstrated a 4.5-cm solitary brain mass in the right basal ganglia with compression along the ventricular system. No other lesion was found in the patient. Histologic and immunohistochemical studies of a stereotactic biopsy of the mass showed a T-cell lymphoproliferative lesion positive for CD3, CD8, CD57, and T-cell intracellular antigen 1 and negative for CD4, CD56, CD30, anaplastic lymphoma kinase, and CD20. A monoclonal T-cell receptor-gamma gene rearrangement was detected by polymerase chain reaction analysis of genomic DNA isolated from paraffin-embedded tumor tissue sections. These findings were consistent with peripheral T-cell lymphoma of cytotoxic/suppressor phenotype, resembling the phenotype of T-cell large granular cell leukemia. To the authors' best knowledge, this represents the first reported case of primary brain T-cell lymphoma with a cytotoxic/suppressor immunophenotype. A brief review of the literature of primary brain T-cell lymphoma is also presented.
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PMID:Primary central nervous system cytotoxic/suppressor T-cell lymphoma: report of a unique case and review of the literature. 1271 53

Peripheral T-cell lymphomas (PTCLs) are a biologically diverse and uncommon group of diseases. Compared to their B-cell counterparts, PTCLs remain largely unexplored and the optimal treatment ill-defined due to disease rarity and biological heterogeneity. For the majority of PTCL subtypes, prognosis is poor with a 5-year overall survival of approximately 30% in most series.The notable exception is ALK-positive anaplastic large-cell lymphoma (ALK-pos ALCL), which has a superior outcome. The international prognostic index can be used to some extent to define risk groups within some PTCL subtypes, including PTCL unspecified (PTCLUS). It is likely that the observed clinical heterogeneity reflects differences at the molecular level. With the more widespread availability of gene expression profiling, it may be possible in the future to further refine the classification of PTCLs and elucidate novel therapeutic targets. Future clinical trials are needed that focus specifically on PTCL to advance our understanding and define the optimal management in this disease.
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PMID:Aggressive peripheral T-cell lymphomas (specified and unspecified types). 1630 91

To glean biological differences and similarities of peripheral T-cell lymphoma-not otherwise specified [PTCL-NOS] to diffuse large B-cell lymphoma (DLBCL), a transcriptosome analysis was done on five PTCL-NOS and four DLBCL patients and validated by quantitative real-time reverse transcription-PCR on 10 selected genes. Normal peripheral blood T cells, peripheral blood B cells, and lymph node were used as controls. The resultant gene expression profile delineated distinct "tumor profile signatures" for PTCL-NOS and DLBCL. Several highly overexpressed genes in both PTCL-NOS and DLBCL involve the immune network, stroma, angiogenesis, and cell survival cascades that make important contributions to lymphomagenesis. Inflammatory chemokines and their receptors likely play a central role in these complex interrelated pathways: CCL2 and CXCR4 in PTCL-NOS and CCL5 and CCR1 in DLBCL. Highly overexpressed oncogenes unique to PTCL-NOS are SPI1, STK6, alpha-PDGFR, and SH2D1A, whereas in DLBCL they are PIM1, PIM2, LYN, BCL2A1, and RAB13. Oncogenes common to both lymphomas are MAFB, MET, NF-kappaB2, LCK, and LYN. Several tumor suppressors are also down-regulated (TPTE, MGC154, PTCH, ST5, and SUI1). This study illustrates the relevance of tumor-stroma immune trafficking and identified potential novel prognostic markers and targets for therapeutic intervention.
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PMID:Transcript profiling in peripheral T-cell lymphoma, not otherwise specified, and diffuse large B-cell lymphoma identifies distinct tumor profile signatures. 1637 2

Peripheral T-cell lymphomas (PTCLs) represent a heterogeneous group of non-Hodgkin's lymphomas. With few exceptions (eg, anaplastic large-cell lymphoma expressing the anaplastic lymphoma kinase), PTCLs have generally been reported to have a worse prognosis compared with B-cell lymphomas. Despite the poor outcome after conventional therapy, the impact of high-dose therapy with autologous or allogeneic stem cell transplantation (SCT) in these rare diseases is poorly defined mainly because of the lack of prospective PTCL-restricted studies. Most data exist for high-dose therapy with autologous SCT in relapsing or refractory disease. Because most studies showed similar results for PTCL compared with aggressive B-cell lymphomas in which high-dose therapy with autologous SCT is accepted as standard therapy, this approach seems appropriate in relapsing or refractory PTCL. Results for high-dose therapy with autologous SCT as first-line therapy mainly rely on studies on aggressive lymphomas that also included lymphomas of the T-cell phenotype. Our own recently published PTCL-restricted prospective study confirmed the feasibility with only moderate toxicity and a good response rate. Overall, patients with a good remission status after induction therapy exhibited a high complete response rate after transplantation, and at least a subgroup of patients remained in long-term remission. The greatest uncertainty exists for the impact of allogeneic SCT after high-dose therapy. In refractory or relapsing PTCL, this approach might improve the outcome for eligible patients, especially when using reduced-intensity conditioning. Overall, because data on high-dose therapy for PTCL are limited, larger and randomized studies are necessary to definitely confirm the preliminary results.
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PMID:The role of high-dose therapy in peripheral T-cell lymphomas. 1664 Aug 12

Peripheral T-cell lymphomas (PTCLs) are a biologically diverse and uncommon group of diseases. Compared to their B-cell counterparts, PTCLs remain largely unexplored and the optimal treatment ill-defined due to disease rarity and biological heterogeneity. With the notable exception of ALK-pos anaplastic large cell lymphoma (ALCL), the prognosis of most PTCL subtypes is extremely is poor with a 5 y overall survival of approximately 15-30% in most series. The international prognostic index has been useful in defining different risk groups within some PTCL subtypes, including PTCL unspecified (PTCLU). Attempts have been made to define disease subgroups within the biologically heterogeneous PTCLU based on T-helper chemokine receptor profile and/or gene expression profiling which may aid in tailoring new therapies. Future clinical trials are needed that focus specifically on PTCL to advance our understanding and define the optimal management in this disease.
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PMID:Peripheral T-cell lymphomas. 1751 49

The International Peripheral T-Cell Lymphoma Project is a collaborative effort designed to gain better understanding of peripheral T-cell and natural killer (NK)/T-cell lymphomas (PTCLs). A total of 22 institutions in North America, Europe, and Asia submitted clinical and pathologic information on PTCLs diagnosed and treated at their respective centers. Of the 1314 eligible patients, 181 had anaplastic large-cell lymphoma (ALCL; 13.8%) on consensus review: One hundred fifty-nine had systemic ALCL (12.1%) and 22 had primary cutaneous ALCL (1.7%). Patients with anaplastic lymphoma kinase-positive (ALK(+)) ALCL had a superior outcome compared with those with ALK(-) ALCL (5-year failure-free survival [FFS], 60% vs 36%; P = .015; 5-year overall survival [OS], 70% vs 49%; P = .016). However, contrary to prior reports, the 5-year FFS (36% vs 20%; P = .012) and OS (49% vs 32%; P = .032) were superior for ALK(-) ALCL compared with PTCL, not otherwise specified (PTCL-NOS). Patients with primary cutaneous ALCL had a very favorable 5-year OS (90%), but with a propensity to relapse (5-year FFS, 55%). In summary, ALK(-) ALCL should continue to be separated from both ALK(+) ALCL and PTCL-NOS. Although the prognosis of ALK(-) ALCL appears to be better than that for PTCL-NOS, it is still unsatisfactory and better therapies are needed. Primary cutaneous ALCL is associated with an indolent course.
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PMID:ALK- anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project. 1838 50

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of rare diseases, usually manifesting clinical aggressiveness. Although important novel insights into the pathobiology of nodal PTCL have been gained recently from molecular profiling studies and clinico-pathological analyses, the pathogenetic molecular lesions remain to be deciphered for most entities. Angioimmunoblastic T-cell lymphoma (AITL) comprises CD4+ CXCL13+ neoplastic cells displaying overlapping immunophenotypical and molecular features with normal follicular helper T cells. This derivation might account for the presence of a prominent non-neoplastic component in AITL tissues and the clinical manifestations of the disease reflective of an immunological dysfunction. ALK+ anaplastic large cell lymphoma (ALCL), defined by ALK gene translocation with various gene partners, is composed of CD30+ ALK+ cells with a cytotoxic phenotype and usually carries a good prognosis. ALK- ALCL, now considered as a distinct disease entity, is morphologically and immunophenotypically similar to ALK+ ALCL, except for ALK expression, but has distinctive molecular features. PTCL, not otherwise specified (PTCL, NOS), the largest PTCL category, which is derived from activated CD4+ (or CD8+) T cells, is markedly heterogeneous, including at the molecular level. Gene expression profiling approaches have identified novel biomarkers of potential therapeutic interest, and suggest the existence of molecularly distinct PTCL, NOS subgroups.
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PMID:Pathobiology and molecular profiling of peripheral T-cell lymphomas. 1907 96

Peripheral T-cell lymphoma (PTCL) is often challenging to diagnose and classify. Gene expression profiling was performed on 144 cases of PTCL and natural killer cell lymphoma and robust molecular classifiers were constructed for angioimmunoblastic T-cell lymphoma (AITL), anaplastic lymphoma kinase-positive (ALK(+)) anaplastic large-cell lymphoma (ALCL), and adult T-cell leukemia/lymphoma. PTCL-unclassifiable was molecularly heterogeneous, but we were able to identify a molecular subgroup with features of cytotoxic T lymphocytes and a poor survival compared with the remaining PTCL-not otherwise specified cases. Many of the pathologic features and substantial components of the molecular signature of AITL are contributed by the follicular dendritic cells, B-cell, and other stromal components. The expression of Th17-associated molecules in ALK(+) ALCL was noted and may represent aberrant activation of Th17-cell differentiation by abnormal cytokine secretion. Adult T-cell leukemia/lymphoma has a homogeneous molecular signature demonstrating high expression of human T-lymphotropic virus type 1-induced genes. These classifiers reflect the biology of the tumor cells as well as their microenvironment. We also constructed a molecular prognosticator for AITL that appears to be largely related to the microenvironmental signature, and the high expression of 2 immunosuppressive signatures are associated with poor outcome. Oncogenic pathways and tumor-host interactions also were identified, and these findings may lead to better therapies and outcome in the future.
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PMID:Molecular signatures to improve diagnosis in peripheral T-cell lymphoma and prognostication in angioimmunoblastic T-cell lymphoma. 2013 72


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