Adenolymphoma ; enzymology ; metabolism ; Humans ; Lymphoma, T-Cell ; enzymology ; metabolism ; Lymphoma, T-Cell, Peripheral ; enzymology ; metabolism ; Male ; Middle Aged ; Nitric Oxide Synthase Type I ; metabolism ; Up-Regulation

OBJECTIVETo detect the expression level of asparagine synthetase (ASNS) in patients with relapsed or refractory extranodal NK/T cell lymphoma and explore its clinical significance.

METHODSTen patients with relapsed or refractory extranodal NK/T cell lymphoma admitted in our department from January, 2013 to January, 2016 were analyzed. The diagnoses were confirmed by pathological and immunohistochemical examination following failed chemotherapies in all cases. Branched DNA-liquidchip technique (bDNA-LCT) was used for detecting ASNS mRNA expression in paraffin-embedded tissue sections in the 10 cases of relapsed or refractory extranodal NK/T cell lymphoma and in 5 cases of chronic rhinitis. The correlations were analyzed between ASNS expression and the clinicopathological features and outcomes of the patients with failed chemotherapy regimens containing asparaginasum.

RESULTSSix out of the 10 patients with relapsed or refractory extranodal NK/T cell lymphoma died due to diseaseprogression. The expression level of ASNS was significantly higher in the lymphoma tissues than in tissue specimens of chronic rhinitis (P<0.05). The expression level of ASNS was associated with the International Prognostic Index (P=0.023) in patients with relapsed or refractory extranodal NK/T cell lymphoma, and Kaplan-Meier curve showed that a high ASNS expression was correlated with a reduced overall survival and progression-free survival of the patients.

CONCLUSIONAsparaginasum-based chemotherapy regimens are recommended for treatment of relapsed or refractory extranodal NK/T cell lymphoma with low ASNS expressions.

Aspartate-Ammonia Ligase ; metabolism ; Disease-Free Survival ; Humans ; Lymphoma, Extranodal NK-T-Cell ; enzymology ; Recurrence

Granzyme B is one of the serine proteases expressed in natural killer (NK) cells and activated cytotoxic T-lymphocytes. To evaluate the usefulness of granzyme B immunoreactivity in the diagnosis of T/NK-cell lymphoma, we studied 69 cases of lymphomas occurring in the upper aerodigestive tract by paraffin-section immunohistochemistry using a commercially available monoclonal antibody to granzyme B (GrB-7). All 19 cases of T/NK-cell lymphomas defined by the expression of CD56 (NHK-1) and one or both T-cell markers (polyclonal CD3 and CD45RO) expressed granular cytoplasmic granzyme B immunoreactivity. Two out of 9 cases of T-cell lymphomas showing no CD56 expression demonstrated strong granzyme B immunoreactivity. No tumor cells among 39 cases of B-cell diffuse large cell lymphomas and 2 cases of null cell diffuse large cell lymphomas were immunoreactive for granzyme B, however a few scattered granzyme B-positive reactive small lymphoid cells were consistently observed. Based on its sensitivity in this study as well as its reactivity in routinely processed tissue sections, even without heat-induced epitope retrieval technique, monoclonal antibody to granzyme B (GrB-7) can be applied as a useful marker in the diagnosis of T/NK-cell lymphomas in conjunction with CD56.
Adult ; Aged ; Aged, 80 and over ; Child ; Female ; Human ; Immunohistochemistry ; Killer Cells/pathology* ; Lymphoma/pathology* ; Lymphoma/enzymology* ; Lymphoma, T-Cell/pathology ; Lymphoma, T-Cell/enzymology* ; Male ; Middle Age ; Serine Endopeptidases/metabolism*

OBJECTIVETo explore the effects of resveratrol-induced apoptosis and autophagy in T-cell acute lymphoblastic leukemia (T-ALL) cells and potential molecular mechanisms.

METHODSThe anti-proliferation effect of resveratrol-induced, apoptosis and autophagy on T-ALL cells were detected by using MTT test, immunofluorescence, electronic microscope, and flow cytometry, respectively. Western blotting was performed for detecting changes of apoptosis-associated proteins, cell cycle regulatory proteins and state of activation of Akt, mTOR, p70S6K, 4E-BP1, and p38-MAPK.

RESULTSResveratrol inhibited the proliferation and induced apoptosis and autophagy in T-ALL cells in a dose and time-dependent manner. It also induced cell cycle arrest at G0/G1 phase via up regulating cyclin-dependent kinase (CDK) inhibitors p21 and p27 and down regulating cyclin A and cyclin D1. Western blotting revealed that resveratrol significantly decreased the expression of antiapoptotic proteins (Mcl-1 and Bcl-2) and increased the expression of proapoptotic proteins (Bax, Bim, and Bad), and induced cleaved-caspase-3 in a time-dependent manner. Significant increase in ratio of LC3-II/LC3-I and Beclin 1 was also detected. Furthermore, resveratrol induced significant dephosphorylation of Akt, mTOR, p70S6K, and 4E-BP1, but enhanced specific phosphorylation of p38-MAPK which could be blocked by SB203580. When autophagy was suppressed by 3-MA, apoptosis in T-ALL cells induced by resveratrol was enhanced.

CONCLUSIONOur findings have suggested that resveratrol induces cell cycle arrest, apoptosis, and autophagy in T-ALL cells through inhibiting Akt/mTOR/p70S6K/4E-BP1 and activating p38-MAPK signaling pathways. Autophagy might play a role as a self-defense mechanism in T-ALL cells treated by resveratrol. Therefore, the reasonable inhibition of autophagy in T-ALL cells may serve as a promising strategy for resveratrol induced apoptosis and can be used as adjuvant chemotherapy for T-ALL.

Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Autophagy ; drug effects ; Cell Culture Techniques ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Flow Cytometry ; Humans ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; enzymology ; pathology ; Proto-Oncogene Proteins c-akt ; antagonists & inhibitors ; Stilbenes ; pharmacology ; T-Lymphocytes ; drug effects ; enzymology ; ultrastructure ; TOR Serine-Threonine Kinases ; antagonists & inhibitors ; p38 Mitogen-Activated Protein Kinases ; metabolism

This study was to investigate the predictive factors influencing prognosis of non-Hodgkin's lymphoma (NHL). The clinical data on 125 cases of NHL were analyzed retrospectively. The results indicated that in 125 cases, the incidence of B cell NHL (B-NHL) was 68%, T cell NHL (T-NHL) was 28%, and uncertained cases were 4%. B-NHL was with more bone marrow involvement, while T-NHL was associated with more presence of B symptom, increased lactate dehydrogenase (LDH), advanced clinical stage and higher International Prognostic Index (IPI) scores. For T-NHL and B-NHL, the 3-year overall survival (OS) rate was 41.07% and 71.64% respectively. Age, B symptom, LDH level, and clinical stage were associated with OS. Immunophenotyping was not identified as a significant prognostic factor. The incidence of born marrow involvement was 31.2%, mainly in B-NHL. The involvement manner had no relationships with age, B symptom, LDH level and T/B immunophenotyping. Diffuse bone marrow involvement was often linked with hepatosplenomegaly, and its OS was shorter than that focal manner. In conclusion, age, B symptom, LDH level and clinical stage affect NHL survival, while immunophenotyping was not an independent prognostic factor for NHL. The manner of bone marrow involvement helped to predict prognosis.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bone Marrow ; pathology ; Child ; Child, Preschool ; China ; Female ; Humans ; Infant ; L-Lactate Dehydrogenase ; metabolism ; Lymphoma, B-Cell ; diagnosis ; Lymphoma, Non-Hodgkin ; diagnosis ; mortality ; pathology ; Lymphoma, T-Cell ; diagnosis ; enzymology ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Survival Rate ; Young Adult

AIMTo study the antitumor mechanism of 3-bromopropionylamino benzoylurea (JIMB01) on leukemia and lymphoma.

METHODSThe antitumor effects of JIMB01 in cell culture was detected by MTT staining. JIMB01-induced apoptosis in leukemia and lymphoma cells was tested by Giemsa staining, fluorescent Hoechst33258 staining, as well as DNA gel electrophoresis. Cell cycle was analyzed by flow cytometry. JIMB01-induced Bcl-2 phosphorylation in CEM cell lines was detected by Western blot methods. The activities of caspase-3 and caspase-8 were determined by colorimetric protease assay and that of caspase-9 was determined by fluorescent intensity.

RESULTSThis compound showed antiproliferative activities in a panel of nine human leukemia and lymphoma cell lines with IC50 values in the range of 0.25 micromol x L(-10 to 0. 51 micromol x L(-1). Morphological observation and cell cycle analysis indicated that CEM cells were blocked at mitosis phase by JIMB01. The fluorescent Hoechst33258 staining showed apoptotic nuclear degradation dispersed in the cytoplasm of CEM cells exposed to JIMB01 at 0. 80 micromol x L(-1) for 24 h. DNA degradation in the form of a multiple-unit DNA ladder was clearly demonstrated in CEM leukemia cells treated with JIMB01 at 0.15 micromol x L(-1) or higher for 24 h using agarose gel electrophoresis. Bcl-2 phosphorylation became visible, in Western blot, within 6 h in CEM cells treated with JIMB01 at 0.15 micromol x L(-1) or higher for 24 h. JIMB01 increased the activities of caspase-3, -8 and -9 in CEM cells; DEVD-fmk, a caspase-3 inhibitor, inhibited the cytotoxicity of JIMB01 in CEM leukemia cells.

CONCLUSIONThe antitumor mechanism of JIMB01 is that JIMB01 may induce tumor cell apoptosis through Bcl-2 phosphorylation and then caspase passway.

Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Caspase 3 ; Caspase 8 ; Caspase 9 ; Caspases ; metabolism ; Cell Division ; drug effects ; DNA Fragmentation ; HL-60 Cells ; Humans ; Leukemia, T-Cell ; enzymology ; metabolism ; pathology ; Lymphoma, B-Cell ; pathology ; Phosphorylation ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Tumor Cells, Cultured ; U937 Cells ; Urea ; analogs & derivatives ; pharmacology

Germ-line mutations in BRCA2 predispose to early-onset cancer. Homozygous mutant mouse, which has Brca2 truncated in exon 11 exhibit paradoxic occurrence of growth retardation and development of thymic lymphomas. However, due to its large embryonic lethality, cohort studies on the thymic lymphomas were not feasible. With the aid of Cre-loxP system, we demonstrate here that thymus-specific disruption of Brca2 allele without crossing it to p53-mutant background leads to the development of thymic lymphomas. Varying from 16 weeks to 66 weeks after birth, 25% of mice disrupted of Brca2 in the thymus died of thymic lymphomas, whereas previous report did not observe lymphomagenesis using similar Cre-loxP system. Future analysis of thymic lymphomas from these mice presented here will provide information on the cooperative mutations that are required for the BRCA2-associated pathogenesis of cancer.
Animals ; BRCA2 Protein/deficiency/*genetics ; CD4-CD8 Ratio ; Cell Separation ; Flow Cytometry ; Integrases/*genetics/immunology ; Lymphoma/*genetics/immunology/metabolism/pathology ; Mice ; Mice, Knockout ; Organ Specificity ; *Sequence Deletion ; T-Lymphocytes/enzymology/*immunology ; Thymus Gland/immunology/metabolism/pathology ; Thymus Neoplasms/*genetics/immunology/metabolism/pathology ; Tumor Suppressor Protein p53/deficiency/genetics/immunology