To determine whether the p53 expression might be a predictor for treatment sponse and overall survival in nodal non-Hodgkin's lymphoma (NHL), we analyzed e expression of p53 in 69 NHL patients. p53 protein expression was analyzed by munohistochemistry with long-term follow up (1-148 months: median 12.2). p53 pression was noted in 23/69 (33.3%) patients. Complete response (CR) rate to stemic chemotherapy was correlated with stage (I/II) (p=0.038), but not with 3 expression (p=0.2856). Poor overall survival was associated with stage =0.0010) or IPI score (p=0.0076), but not with p53 expression (p=0.8601). From ratification analysis by stage, in stage III/IV patients, the p53 positive oup had a trend to be associated with poor overall survival than the p53 gative group. Multivariate analysis revealed that p53 positive group was sociated with less CR rate compared to the p53 negative group (p=0.046), ereas overall survival was correlated with stage (p=0.0320), not with p53 atus. p53 expression was associated with less CR rate in patients with DLBL. rther studies with large numbers of samples and homogenous group of NHL are eded to determine the prognostic value of cell cycle regulator, p53 in NHL.
Antibodies, Monoclonal ; Cell Cycle Proteins/biosynthesis ; Female ; Gene Expression ; Human ; Immunohistochemistry ; Immunophenotyping ; Lymph Nodes/pathology* ; Lymph Nodes/metabolism* ; Lymphoma, Non-Hodgkin/pathology* ; Lymphoma, Non-Hodgkin/metabolism* ; Lymphoma, Non-Hodgkin/genetics ; Lymphoma, Non-Hodgkin/drug therapy ; Male ; Middle Age/Mpartment of Microbiology ; Prognosis ; Protein p53/immunology ; Protein p53/genetics ; Protein p53/biosynthesis*

No abstract available.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Cyclophosphamide/therapeutic use ; Doxorubicin/therapeutic use ; Female ; Humans ; Immunoglobulin Variable Region/genetics ; Leukemia, Hairy Cell/drug therapy/*genetics/pathology ; Lymphoma, Non-Hodgkin/drug therapy/*genetics/pathology ; MAP Kinase Kinase 1/*genetics ; Male ; Middle Aged ; Mutation ; Polymorphism, Single Nucleotide ; Prednisone/therapeutic use ; Pregnancy ; Proto-Oncogene Proteins B-raf/*genetics ; Real-Time Polymerase Chain Reaction ; Vincristine/therapeutic use

Hepatitis C virus (HCV) is one of the main viral causes of hepatocellular carcinoma (HCC) and is associated with lymphoproliferative disorder such as non-Hodgkin's lymphoma (NHL). However, there are only few case reports on concomitantly induced NHL and HCC by HCV. Herein, we report a case of synchronous NHL and HCC in a patient with chronic hepatitis C which was unexpectedly diagnosed during liver transplantation surgery. This case suggests that although intrahepatic lymph node enlargements are often considered as reactive or metastatic lymphadenopathy in chronic hepatitis C patients with HCC, NHL should also be considered as a differential diagnosis.
Antineoplastic Agents/therapeutic use ; Carcinoma, Hepatocellular/complications/*diagnosis/radiotherapy ; Drug Therapy, Combination ; Embolization, Therapeutic ; Fluorodeoxyglucose F18 ; Gadolinium DTPA ; Genotype ; Hepatitis B virus/genetics ; Hepatitis C, Chronic/complications/*diagnosis/*virology ; Humans ; Liver Neoplasms/complications/*diagnosis/radiotherapy ; Lymph Nodes/pathology ; Lymphoma, Non-Hodgkin/complications/*diagnosis/drug therapy ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Positron-Emission Tomography ; Tomography, X-Ray Computed

Acute graft-versus-host disease (aGVHD) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the mechanisms of aGVHD are not well understood. We aim to investigate the roles of the three angiogenic factors: angiopoietin-1 (Ang-1), Ang-2 and vascular endothelial growth factor (VEGF) in the development of aGVHD. Twenty-one patients who underwent allo-HSCT were included in our study. The dynamic changes of Ang-1, Ang-2 and VEGF were monitored in patients before and after allo-HSCT. In vitro, endothelial cells (ECs) were treated with TNF-β in the presence or absence of Ang-1, and then the Ang-2 level in the cell culture medium and the tubule formation by ECs were evaluated. After allo-HSCT, Ang-1, Ang-2 and VEGF all exhibited significant variation, suggesting these factors might be involved in the endothelial damage in transplantation. Patients with aGVHD had lower Ang-1 level at day 7 but higher Ang-2 level at day 21 than those without aGVHD, implying that Ang-1 may play a protective role in early phase yet Ang-2 is a promotion factor to aGVHD. In vitro, TNF-β promoted the release of Ang-2 by ECs and impaired tubule formation of ECs, which were both weakened by Ang-1, suggesting that Ang-1 may play a protective role in aGVHD by influencing the secretion of Ang-2, consistent with our in vivo tests. It is concluded that monitoring changes of these factors following allo-HSCT might help to identify patients at a high risk for aGVHD.
Acute Disease ; Adolescent ; Adult ; Angiogenesis Inducing Agents ; immunology ; metabolism ; pharmacology ; Angiopoietin-1 ; genetics ; immunology ; pharmacology ; Angiopoietin-2 ; genetics ; immunology ; pharmacology ; Antineoplastic Agents ; therapeutic use ; Female ; Gene Expression Regulation, Neoplastic ; Graft vs Host Disease ; genetics ; immunology ; pathology ; Hematopoietic Stem Cell Transplantation ; Human Umbilical Vein Endothelial Cells ; cytology ; drug effects ; immunology ; Humans ; Leukemia, Myeloid ; genetics ; immunology ; pathology ; therapy ; Lymphoma, Non-Hodgkin ; genetics ; immunology ; pathology ; therapy ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; immunology ; pathology ; therapy ; Retrospective Studies ; Signal Transduction ; Transplantation, Homologous ; Tumor Necrosis Factor-alpha ; pharmacology ; Vascular Endothelial Growth Factor A ; genetics ; immunology

OBJECTIVETo explore the expression and clinical significance of P-glycoprotein (P-gp)/mdr1mRNA, multidrug resistance-associated protein (MRP) and lung resistance protein (LRP) in newly diagnosed non-Hodgkin's lymphoma.

METHODSmdr1 mRNA of in 41 patients with non-Hodgkin's lymphoma was assayed by semi-quantitative RT-PCR. The expressions of P-gp, MRP and LRP proteins in lymph node viable blasts were identified by flow cytometry. The results were compared with those obtained from control cases, and the correlation of the changes with clinical outcomes was analyzed.

RESULTS(1) Among the 41 cases, the positive expression of P-gp protein was detected in 8 cases, MRP in 7 cases, LRP in 15 cases, and mdr 1 mRNA in 11 cases. (2) The P-gp and LRP levels in NHL were significantly higher than those in control group, but MRP wasn't. The P-gp over-expression was significantly associated with mdr1mRNA (r = 0.396, P = 0.01). No correlation was showed among the expressions of P-gp, MRP and LRP. (3) Patients with P-gp expression had a poorer outcome of chemotherapy than those with P-gp-negative (P = 0.005). P-gp expression was significantly associated with higher clinical stage (P = 0.046) and elevated serum lactate dehydrogenase level (P = 0.032), but not associated with malignant degree (P = 0.298). MRP had no impact on the outcome of chemotherapy (P = 0.212), and wasn't significantly associated with higher clinical stage (P = 0.369), elevated LDH (P = 0.762) and higher malignant degree (P = 0.451). Patients with LRP expression had a poorer outcome of chemotherapy than those LRP-negative (P = 0.012). LRP expression was significantly associated with higher clinical stage (P = 0.0019), elevated LDH (P = 0.02) and higher malignant degree (P = 0.01).

CONCLUSIONThe data of this study indicate that P-gp and LRP expressions but not MRP expression are important in the mechanism of drug resistance associated with a poor clinical outcome in previously untreated NHL.

ATP Binding Cassette Transporter, Sub-Family B ; ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; metabolism ; Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cell Line, Tumor ; Child ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Female ; Humans ; Lactate Dehydrogenases ; blood ; Lymph Nodes ; metabolism ; Lymphoma, Non-Hodgkin ; drug therapy ; metabolism ; pathology ; Male ; Middle Aged ; Multidrug Resistance-Associated Proteins ; metabolism ; Neoplasm Staging ; RNA, Messenger ; metabolism ; Remission Induction ; Vault Ribonucleoprotein Particles ; metabolism ; Young Adult