ABSTRACT
Objective: This study attempted to identify altered metabolism and pathways related to non-Hodgkin's lymphoma [NHL] and myeloma patients
Materials and Methods: In this retrospective study, we collected plasma samples from 11 patients-6 healthy controls with no evidence of any blood cancers and 5 patients with either multiple myeloma [n=3] or NHL [n=2] during the preliminary study period. Samples were analyzed using quadrupole time-of-flight liquid chromatography mass spectrometry [LC-MS]. Significant features generated after statistical analyses were used for metabolomics and pathway analysis
Results: Data after false discovery rate [FDR] adjustment at q=0.05 of features showed 136 for positive and 350 significant features for negative ionization mode in NHL patients as well as 262 for positive and 98 features for negative ionization mode in myeloma patients. Kyoto Encyclopedia of Genes and Genomes [KEGG] pathway analysis determined that pathways such as steroid hormone biosynthesis, ABC transporters, and arginine and proline metabolism were affected in NHL patients. In myeloma patients, pyrimidine metabolism, carbon metabolism, and bile secretion pathways were potentially affected by the disease
Conclusion: The results have shown tremendous differences in the metabolites of healthy individuals compared to myeloma and lymphoma patients. Validation through quantitative metabolomics is encouraged, especially for the metabolites with significantly expression in blood cancer patients
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Lymphoma, Non-Hodgkin/metabolism , Gas Chromatography-Mass Spectrometry , Retrospective StudiesABSTRACT
To investigate the role of cyclin B1 and cdc2 in the pathogenesis and progression of malignant lymphoma, 68 cases of nodal non-Hodgkin's lymphoma were examined about the expression of cyclin B1 and cdc2 along with p53 and Ki-67 by immunohistochemical method. The correlation of their expression with various clinicopathologic findings was also analyzed. Cyclin B1 and cdc2 were diffusely expressed in 39 cases (57.4%) and 54 cases (79.4%) out of 68 cases studied, respectively. The mean labeling indices of cyclin B1 and cdc2 in malignant lymphoma were 31.9% and 68.0%, respectively. In normal lymphoid tissues, cyclin B1 and cdc2 were expressed predominantly in the germinal center with mean labeling indices of 13.9% and 28.3%, respectively. The correlation between the expression of cyclin B1 and cdc2 was noted (p=0.013). The expression of Ki-67 was correlated with that of cyclin B1 (p=0.023) and marginally correlated with that of cdc2 (p=0.056). The expression of cdc2 and p53 in complete remission group to chemotherapy was lower than that of progressive disease group (p=0.047, p=0.049). In multivariate analysis, the clinical stage alone showed significance on overall survival (p=0.049). In conclusion, cyclin B1 and cdc2 appeared to be involved in the genesis or progression of malignant lymphoma and cdc2 can be a useful marker for response to chemotherapy.
Subject(s)
Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Male , Middle Aged , CDC2 Protein Kinase/biosynthesis , Cyclin B/biosynthesis , Cyclin B1 , Immunohistochemistry , Ki-67 Antigen/biosynthesis , Lymph Nodes/metabolism , Lymphoma, Non-Hodgkin/metabolism , Palatine Tonsil/metabolism , Predictive Value of Tests , Prognosis , Survival Analysis , Tumor Suppressor Protein p53/biosynthesisABSTRACT
P 53 positivity and PCNA labelling index were studied in 50 cases of node based Non Hodgkin's lymphomas, P 53 positivity was observed in a spectrum of these disorders, suggesting that P 53 mutations play a role in the genesis of these tumours. P 53 positivity incresed from low through intermediate to high grade tumours and thus may be of prognostic value in these lesions. PCNA labelling index (LI) was higher in high grade tumours. P 53 and PCNA immunoreactivity showed a relationship in that PCNA LI was seen to be more than 30% in P 53 positive tumours. P 53 positivity appears to be related to the subtype and proliferation rate of NHL.
Subject(s)
Humans , Immunohistochemistry , Lymphoma, Non-Hodgkin/metabolism , Prognosis , Proliferating Cell Nuclear Antigen/metabolism , Tumor Suppressor Protein p53/metabolismABSTRACT
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.
Subject(s)
Female , Humans , Male , Antibodies, Monoclonal , Cell Cycle Proteins/biosynthesis , Gene Expression , 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 , Middle Aged , Prognosis , Tumor Suppressor Protein p53/immunology , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/biosynthesisABSTRACT
O emprego de quimioterapia em tumores de alta replicaçäo celular é responsável pela liberaçäo de constituintes celulares, que podem levar a sérias alteraçöes metabólicas. Estas alteraçöes compreendem distúrbios no metabolismo do: potássio, cálcio, fosfato, uréia e ácido úrico; que caracterizam a SINDROME de LISE TUMORAL AGUDA (SLTA). No período de 29/03/93 a 23/08/93, foram estudados 20 pacientes com hemopatias malignas, com indicaçäo de tratamento poliquimioterápico. Estes pacientes receberam hiper-hidrataçäo com 2000ml/m2 de soluçäo fisiológico 0,9 por cento e alopurinol 200mg/m2 iniciando-se no dia anterior até o último dia de quimioterapia. O diagnóstico de SLTA foi considerado nos pacientes que nos 4 dias do tratamento, apresentaram duas ou mais das seguintes alteraçöes metabólicas: aumento de 25 por cento nos níveis de potássio, ácido úrico, uréia e fosfato; ou diminuiçäo de 25 por cento no nível de cálcio sérico. A SINDROME DE LISE TUMORAL AGUDA CLINICA (SLTAC), foi definida como SLTAC, associada a condiçöes clínicas que implicassem em risco de vida nenhum dos nossos pacientes apresentou SLTAC e apenas 30 por cento desenvolveram SLTAL, demonstrando que este esquema de tratamento foi efetivo.