ABSTRACT
BACKGROUND: The evaluation of the clinical effects of Tacrine has shown efficacy in delaying the deterioration of the symptoms of Alzheimer's disease, while confirming the adverse events consisting mainly in the elevated liver transaminase levels. The study of tacrine analogs presents a continuous interest, and for this reason we establish Quantitative Structure-Activity Relationships on their Acetylcholinesterase inhibitory activity. RESULTS: Ten groups of new developed Tacrine-related inhibitors are explored, which have been experimentally measured in different biochemical conditions and AChE sources. The number of included descriptors in the structure-activity relationship is characterized by 'Rule of Thumb'. The 1502 applied molecular descriptors could provide the best linear models for the selected Alzheimer's data base and the best QSAR model is reported for the considered data sets. CONCLUSION: The QSAR models developed in this work have a satisfactory predictive ability, and are obtained by selecting the most representative molecular descriptors of the chemical structure, represented through more than a thousand of constitutional, topological, geometrical, quantum-mechanical and electronic descriptor types.
Subject(s)
Acetylcholinesterase/chemistry , Cholinesterase Inhibitors/chemistry , Models, Molecular , Tacrine/analogs & derivatives , Tacrine/chemistry , Alzheimer Disease/drug therapy , Alzheimer Disease/enzymology , Cholinesterase Inhibitors/therapeutic use , Datasets as Topic , Humans , Structure-Activity Relationship , Tacrine/therapeutic useSubject(s)
Gene Expression Regulation, Neoplastic/immunology , Immunoglobulin Light Chains/biosynthesis , Immunoglobulin Light Chains/genetics , Lymphoma, B-Cell/complications , Lymphoma, B-Cell/diagnosis , Plasmacytoma/complications , Plasmacytoma/diagnosis , Base Sequence , Clone Cells/immunology , Clone Cells/pathology , Humans , Lymphoma, B-Cell/genetics , Male , Middle Aged , Molecular Sequence Data , Plasmacytoma/geneticsSubject(s)
Antibodies, Monoclonal, Murine-Derived/therapeutic use , Antigens, CD20/metabolism , Burkitt Lymphoma/drug therapy , Cell Transformation, Neoplastic/pathology , Liver Transplantation , Lymphoproliferative Disorders/drug therapy , Antigens, CD20/genetics , Base Sequence , Burkitt Lymphoma/genetics , Burkitt Lymphoma/pathology , Cell Transformation, Neoplastic/genetics , Fatal Outcome , Female , Gene Expression Regulation, Neoplastic , Humans , Immunoglobulin Light Chains/biosynthesis , Immunoglobulin Light Chains/genetics , Liver Transplantation/pathology , Lymphoproliferative Disorders/genetics , Lymphoproliferative Disorders/pathology , Middle Aged , Molecular Sequence Data , RituximabABSTRACT
A patient with history of B cell lymphoma treated with rituximab-based chemotherapy relapsed with a blastic CD4+/CD56+ neoplasm that was negative for CD20, CD79a and CD3. The relapse morphology and immunophenotyping were unusual and plasmacytoid dendritic cell (PDC) tumor enters the differential diagnosis. However, expressions of Oct-2 and CD10 in the relapse tumor were both more compatible with B cell than PDC lineage. Molecular investigations showed clonal rearrangements for both immunoglobulin heavy chain (IgH) and T cell receptor (TCR) gamma chain gene by polymerase chain reaction (PCR). Furthermore, a clonal relationship with the original B cell lymphoma was demonstrated for all PCR products. Our case illustrated the potential pitfalls and ambiguity of lineage classification based on morphology and immunophenotyping alone, especially for rare and poorly defined entities.
Subject(s)
CD4 Antigens/analysis , CD56 Antigen/analysis , Lymphoma, B-Cell/pathology , Aged, 80 and over , Antigens, CD20/analysis , Base Sequence , Dendritic Cells/metabolism , Dendritic Cells/pathology , Diagnosis, Differential , Flow Cytometry , Gene Rearrangement , Humans , Immunoglobulin Heavy Chains/genetics , Immunophenotyping , Karyotyping , Lymphoma, B-Cell/genetics , Lymphoma, B-Cell/metabolism , Male , Molecular Sequence Data , Neoplasm Recurrence, Local , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/pathology , Octamer Transcription Factor-2/analysis , Polymerase Chain Reaction , Receptors, Antigen, T-Cell, gamma-delta/genetics , Sequence Homology, Nucleic AcidABSTRACT
A patient with a history of precursor B-cell leukemia presented with an isolated ulcerating gum lesion 8 years after allogeneic stem cell transplantation with severe graft versus host disease. A biopsy revealed an undifferentiated malignant hemic lesion. Examinations of the peripheral blood and marrow were normal. Molecular studies confirmed clonal relationship between the gum lesion with the original marrow disease, despite the anatomical, histological and chronological separations.
