bromochloroacetic-acid and Leukemia

The cytoskeleton (CSK) of eukaryotic cells is composed of a complex interconnected network of filaments which is important in a wide variety of cellular functions including changes in cell shape, cell motility, mitosis, anchorage-dependent growth, and the localization of cellular organelles such as mitochondria, polyribosomes, and secretory granules. The various proteins comprising the cytoskeleton include actin in microfilaments, tubulin in microtubules, and the heterogeneous group of intermediate filament proteins that are associated with different cell types (keratin in epithelial cells, vimentin in fibroblasts, desmin in muscle cells, glial filament protein in glial cells, and the neurofilament protein subunits in neural tissue). Many other proteins in glial cells, and the neurofilament protein subunits in neural tissue). Many other proteins are closely associated with the cytoskeleton and influence its organization. In neoplastic cells, the expression of these different CSK proteins, especially the intermediate filament proteins, reflects their morphologic and functional differentiation. The carcinomas contain keratin; identification of individual keratin components may allow further sub-classification of carcinomas which is consistent with their tissue of origin. The sarcomas of muscle origin contain desmin. Vimentin is found primarily with cells of mesenchymal origin, but may coexist with other intermediate filament proteins in other tumors. One example is the coexistence of keratin and vimentin in tumors, such as mesotheliomas, which are derived from epithelial cells of embryonic origin. Glial fibrillary acidic protein is the most specific marker for glial tumors. Tumors of neural origin are characterized by the presence of neurofilament subunits. Therefore, analysis of CSK composition would be useful in diagnosis of clinical specimens and aid in studies of lineage relationships of neoplasms. Although no consistent differences in cytoskeletal structure between neoplastic and normal cells have been identified so far, the presence of more subtle biochemical alterations in the cytoskeletal structure of neoplastic cells that contributes to malignant behavior has not been ruled out. Since the cytoskeletal network plays an important role in cell shape and cell locomotion, which in turn are thought to be involved in growth control, invasion, and metastasis, further work is directed at identifying the various alterations in cytoskeletal architecture that

Topics: Actin Cytoskeleton; Actins; Animals; Astrocytes; Carcinoma; Cell Differentiation; Cell Division; Cell Transformation, Neoplastic; Cytoskeletal Proteins; Cytoskeleton; Desmin; Epithelium; Glial Fibrillary Acidic Protein; Glioma; Granulocytes; Humans; Intermediate Filament Proteins; Keratins; Leukemia; Lymphoma; Macrophages; Microtubules; Molecular Weight; Muscles; Neoplasm Metastasis; Neoplasms; Neoplasms, Nerve Tissue; Neurons; Sarcoma; Tissue Distribution; Vimentin

Killer cell immunoglobulin-like receptors (KIRs) recognize different groups of Human Leukocyte Antigen (HLA) class I alleles and are expressed by natural killer (NK) cells and some T lymphocytes. NK cell cytotoxicity is triggered by failure to recognize the appropriate HLA class I ligand on target cells. Recently, it has been shown that HLA class I ligand incompatibility in the graft-versus-host (GvH) direction is associated with a better outcome in haploidentical hematopoietic stem cell transplantation (HSCT). Since KIR genotypes are very diverse in the population, we explored whether or not the donor KIR genotype could affect the graft-versus-leukemia (GvL) effect in the related HLA-identical HSCT setting. We determined the KIR and HLA genotypes of 65 HLA-identical patient-donor siblings. We found that the presence of two activating KIRs, 2DS1 and 2DS2, in the donor was significantly associated with a decreased leukemic relapse rate (P=0.03; OR=0.18; 95% CI: 0.037-0.88). Moreover, the probability of relapse at 5 years was significantly lower for patients who received a graft from a donor with the 2DS1(+)2DS2(+) genotype than for those who received a transplant from other donors (17 vs 63%, respectively; P=0.018). In conclusion, this study suggests that a joint effect of these two selected activating KIRs in the donor might confer some protection against leukemic relapse.

Topics: Adolescent; Adult; Child; Child, Preschool; Female; Genotype; Graft vs Host Disease; Graft vs Leukemia Effect; Hematopoietic Stem Cell Transplantation; Histocompatibility; Histocompatibility Testing; Humans; Keratin-2; Keratins; Killer Cells, Natural; Leukemia; Leukocyte Transfusion; Male; Middle Aged; Receptors, Immunologic; Receptors, KIR; Secondary Prevention; Survival Analysis

Topics: Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Bone Marrow; Esophageal Neoplasms; Gene Expression; Humans; Immunohistochemistry; Keratins; Leukemia; Lung Neoplasms; Male; Neoplasms, Second Primary; Radiotherapy

Aberrant expression of cytokeratins (CK) is known to occasionally occur in malignant lymphomas. The monoclonal mouse-anti-human CK cocktail CK22 recognizes keratin polypeptides with a wide range of molecular weights and can be applied in diagnostic panels for tumors of unknown origin. Using tissue microarray technology, we tested 1059 lymphoma and acute leukemia cases, covering the most common disease entities, for aberrant CK expression, using CK22. In total, 866 of the arrayed cases were evaluable (80%), and 13 positive cases (1.5%) were found: 1 out of 230 Hodgkin lymphomas (0.4%), 1 plasma cell myeloma, 2 out of 326 diffuse large B-cell lymphomas (0.6%), 5 out of 18 mantle cell lymphomas (26%), 3 out of 70 small cell lymphomas/chronic lymphocytic leukemias (4%) and 1 out of 27 peripheral T-cell lymphomas, not otherwise specified (4%). Immunostaining was finely granular in most cases, and the total amount of positively staining cells exceeded 10% only in the cases of Hodgkin lymphoma and plasmocytoma. All CK22-positive cases, except for one mantle cell lymphoma, expressed the specific simple epithelial CK8 but not the basal/stratified epithelial CK5/6. Aberrant CK expression can be encountered in a small subset of otherwise characteristic B- and T-cell lymphomas, but not in acute leukemias, which should be considered in difficult differential diagnostic settings.

Topics: Adult; Aged; Aged, 80 and over; Diagnosis, Differential; Europe; Female; Humans; Immunohistochemistry; Keratins; Leukemia; Lymphoma; Male; Middle Aged; Tissue Array Analysis

To compare gene expression profiles of pancreatic adenocarcinoma tissue specimens, human pancreatic and colon adenocarcinoma and leukemia cell lines and normal pancreas samples in order to distinguish differentially expressed genes and to validate the differential expression of a subset of genes by quantitative real-time RT-PCR (RT-QPCR) in endoscopic ultrasound-guided fine needle aspiration (EUS-guided FNA) specimens.. Commercially dedicated cancer cDNA macroarrays (Atlas Human Cancer 1.2) containing 1176 genes were used. Different statistical approaches (hierarchical clustering, principal component analysis (PCA) and SAM) were used to analyze the expression data. RT-QPCR and immunohistochemical studies were used for validation of results.. RT-QPCR validated the increased expression of LCN2 (lipocalin 2) and for the first time PLAT (tissue-type plasminogen activator or tPA) in malignant pancreas as compared with normal pancreas. Immunohistochemical analysis confirmed the increased expression of LCN2 protein localized in epithelial cells of ducts invaded by carcinoma. The analysis of PLAT and LCN2 transcripts in 12 samples obtained through EUS-guided FNA from patients with pancreatic adenocarcinoma showed significantly increased expression levels in comparison with those found in normal tissues, indicating that a sufficient amount of high quality RNA can be obtained with this technique.. Expression profiling is a useful method to identify biomarkers and potential target genes. Molecular analysis of EUS-guided FNA samples in pancreatic cancer appears as a valuable strategy for the diagnosis of pancreatic adenocarcinomas.

Topics: Acute-Phase Proteins; Adenocarcinoma; Biomarkers, Tumor; Biopsy, Fine-Needle; Cell Line, Tumor; Colonic Neoplasms; Endosonography; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genes, Neoplasm; Humans; Keratin-7; Keratins; Leukemia; Lipocalin-2; Lipocalins; Pancreatic Neoplasms; Prognosis; Proto-Oncogene Proteins; Reproducibility of Results; Reverse Transcriptase Polymerase Chain Reaction; Tissue Plasminogen Activator

Cytokeratin K19 (CK19) expression was evaluated by a reverse transcription PCR method (RT-PCR) in the RNA obtained from peripheral blood stem cell collections (PBSC) from four patients with breast cancers (BC) and 34 mononucleated blood cell (MBC) negative controls (17 PBMC from normal subjects 12 PBSC from different types of leukaemias--M3, M4Eo, M2, etc.--and two from patients with Hodgkin's lymphoma; and three bone marrow (BM) collections). Two BC tissues were taken as positive controls. The method studied (Datta YH, Paul T, Adams PT, Drobyski WR. Sensitive detection of occult breast cancer by reverse transcription polymerase chain reaction. J Oncol 1994;12:475-8) is sensitive enough to allow the detection of CK19 transcripts in a 10(-6) dilution of cDNA reverse transcribed from 1 microgram of BC RNA, but CK19 transcripts were also detected in 64% of the RNA obtained from the MBC controls. However, the amplified product detected in the control samples represents the transcript of the CK19 gene as confirmed by the results of Mae III digestion. It should be pointed out that although the CK19 expression was detected, the levels of expression in PBMC were almost negligible for they disappeared at 1:5 cDNA dilution. Moreover, a direct relationship between the number of BC cells added to PBMC and the increasing dilution levels of the cDNA necessary to prevent CK19 expression was observed. This allows us to conclude that the cDNA dilutions make it possible to distinguish the false from the true positive samples and that, in addition, the cDNA dilutions inform about the degree of BC cell contamination.

Topics: Breast Neoplasms; Case-Control Studies; DNA, Complementary; DNA, Neoplasm; Evaluation Studies as Topic; Female; Gene Expression; Hematopoietic Stem Cells; Hodgkin Disease; Humans; Keratins; Leukemia; Leukocytes, Mononuclear; Polymerase Chain Reaction; Sensitivity and Specificity

Using four human tumor cell lines, MCF-7 and T47-D from breast tumors, MOLT-4 and K-562 from leukemia, flow cytometric DNA analysis of pure and mixed cell population was performed using monoclonal antibodies to cytokeratin to distinguish cytokeratin-containing carcinoma cells from leukemia cells which do not contain cytokeratins. Surprisingly, on pure or mixed K-562 cells, we found positive labeling with KL1, CK8, and CK18 antibodies (results confirmed by immunocytology). This preliminary study has allowed a DNA analysis on epithelial cells of human breast tumors.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Breast Neoplasms; Cell Line; DNA, Neoplasm; Flow Cytometry; Humans; Keratins; Leukemia; Tumor Cells, Cultured